issn: 1301-062x turkish journal of · pdf filenerses bebek, candan gürses, anna elina...

ISSN: 1301-062X

www.noroloji.org.tr

Official Journal of the Turkish Neurological Society

Perspectives

� Neurologists may Perform Interventional Neuroangiography. Yes Reha Tolun

� Diagnostic and Interventional Neuroradiology: Who Should and How? Civan Işlak

Reviews

� The Relationship Between Migraine and Nutrition Ayçıl Özturan, Nevin Şanlıer, Özlem Coşkun

� Intraoperative Neuromonitoring Kubilay Varlı

Research Articles

� EMG and MRI Finding of Suspected Radiculopathy Yıldız Arslan, Ebru Yaşar, Yaşar Zorlu

� Absence Status Epilepticus and Magnetic Resonance Spectroscopy Findings Zeynep Aydın Özemir, Betül Baykan, Ebru Nur Vanlı Yavuz, Serra Sencer

� Unusual Epileptic Activities of Hippocampal Sclerosis Ebru Nur Vanlı Yavuz, Hakan Yener, Zeynep Aydın Özemir, Nerses Bebek, Candan Gürses, Ayşen Gökyiğit, Betül Baykan

� Cerebral Localization in Hyperemesis Gravidarum Hakan Ahmet Ekmekçi, Arzu Setenay Yılmaz, Muhammet Üsame Öziç, Yüksel Özbay, Özlem Seçil Kerimoğlu, Çetin Çelik, Şerefnur Öztürk

Case Reports

� Hemichorea and Hemiballism Associated With Cerebral Vascular Malformation Induced by Hyperglycemia Ferda Selçuk, Mine Hayriye Sorgun, Süha Akpınar

� A Different Progressive Myoclonic Epilepsy: A Case Report Ebru Nur Vanlı Yavuz, Güneş Altıokka, Zeliha Matur, Mikko Muona,

Nerses Bebek, Candan Gürses, Anna Elina Lehesjoki,

Ayşen Gökyiğit, Betül Baykan

Images in Clinical Neurology

� A Case of Neuromyelitis Optica Presenting with Area Postrema Syndrome Derya Kaya, Egemen İdiman, Fethi İdiman, Onur Bulut,

Nuri Karabay

� Cystic Lesions in Spinal Astrocytoma Ahmet Evlice, Dilek İşcan, Meltem Demirkıran

� Intracranial Hematoma in Herpes Simplex Encephalitis Özlem Ethemoğlu, Mehmet Fırat, Kadri Burak Ethemoğlu,

Mehtap Kocatürk

Frontiers in Neurology

� An Approved Treatment in Periodic Paralyses: Diclorphenamide Mine Sezgin

� Clopidogrel Effect on Migraine Patients with ASD Closure Halil İbrahim Akçay, Murat Kürtüncü

Journal ofTurkish

NeurologyVolume: 22 Issue: 2 June 2016

www.tjn.org.tr

A-I

Offical Journal of the Turkish Neurologial Society

Owner

On Behalf of Turkish Journal of Neurology Şerefnur Öztürk

Editorial Manager

Burak Tokdemir

ISSN: 1301-062X

Publishing House

Molla Gürani Mah. Kaçamak Sk. No: 21, 34093 F›nd›kzade-‹stanbul-Turkey Phone: +90 212 621 99 25 Fax: +90 212 621 99 27 [email protected] - www.galenos.com.trPrinting at: Özgün Ofset Ticaret Ltd. Şti.Yeşilce Mah. Aytekin Sk. No: 21 34418 4.Levent/İstanbul-Turkey Phone: +90 212 280 00 09 (pbx)

Date of printing: June 2016Turkish Journal of Neurology is a periodical scientific journal published quarterly.

ContactMurat Kürtüncü (Editor)İstanbul University, Faculty of MedicineDepartment of Neurologyİstanbul, 34093, TurkeyE-mail: [email protected]

The Journal is printed on acid-free paper.

Editör in Chief: Murat Kürtüncü Associate EditorsAslı Tuncer, Uğur Uygunoğlu, Tuncay Gündüz

Editorial Advisory Board

Biostatistical ConsultantErgun Karaağaoğlu

International Advisory Board

Editorial AssistantBurak Tokdemir

Previous EditorsOğuz Tanrıdağ Barış Baklan Kaynak Selekler Tülay Kansu Yeşim Gülşen Parman

Turkish and English Language Editor- English TranslatorDavid Chapman, Can Kavaklıoğlu, Murat Mert Atmaca, Mustafa Çelik, Bedia Marangozoğlu

Cenk AkbostancıAyşe AltıntaşHülya ApaydınBerna Arda (Etik)Semih Ayta Esra BattaloğluBetül BaykanCanan Aykut Bingöl Hayrünnisa BolayRaif ÇakmurNeşe ÇelebisoyBeyazıt Çırakoğlu (Genetik)Turgay DalkaraGülşen Akman DemirBülent ElibolMurat EmreMefküre EraksoySevim ErdemMustafa Ertaş Haşmet HanağasıBirsen İnceTülay KansuRana KarabudakDilaver Kaya

Ayşe Sağduyu KocamanReha Kuruoğlu Zeki OdabaşıPiraye OflazerZülküf M. ÖnalTayfun Özçelik (Genetik)Sibel ÖzekmekçiÇiğdem Özkara Mehmet ÖzmenoğluŞerefnur ÖztürkYakup SarıcaSerap SaygıAksel SivaH. Özden ŞenerHadiye ŞirinErsin TanMehmet Akif TopçuoğluEsen Saka TopçuoğluErdem TüzünDerya Uğurlu UludüzHilmi UysalGörsev YenerSeher Naz YeniMehmet Zarifoğlu

Stanley Appel, USAZohar Argov, IsraelValery Askanas, USANathan Bornstein, IsraelDavid Burke, AustraliaStefano Cappa, ItalyPatricia S. Churchland, USAJames J Corbett, USAIoannis Evdokimidis, GreeceGerald M. Fenichel, USAMarc Fisher, USAMurat Güner, USAWolfgang Grisold, AustraliaHumayan Gültekin, USAAhmet Hoke, USAAlbena Jordanova, Belgium

Howard S. Kirshner, USAAndrew Lees, EnglandMarsel Mesulam, USASoheyl Noachtar, GermanyDavide Pareyson, ItalyViolaine Plante-Bordeneuve, FranceAntony Reder, USAGerard Said, FranceBenjamin Seltzer, USAJaroslaw Slawek, PolandGioacchino Tedeschi, ItalyEduardo Tolosa, SpainBrian Weinshenker, USASandra Weintraub, USA

Volume

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Journal ofTurkish

Neurology

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The Turkish Journal of Neurology has been published quarterly in March, June, September and December as the official journal of the Turkish Neurological Society since 1995. The journal has been also available on-line since 2004. A peer-reviewed system is used to select manuscripts. The languages of the journal are Turkish and English. Original research articles are particularly supported and encouraged.The journal aims to update knowledge of neurology throughout Turkey with research articles, reviews, case reports, short communications, letters to the editor, and clinical images in the field of neurology. To retain interdisciplinary transfer of information between the areas of neuroscience and to undertake a novel effort in the international representation and attribution of published articles are the other aims of the journal. The target readers of the Turkish Journal of Neurology include neurologists and neurology residents as well as other physicians working in the field of neurological sciences. Turkish Journal of Neurology is indexed in Emerging Sources Citation Index (ESCI), Scopus, Directory of Open Access Journals (DOAJ), Chemical Abstracts Service (CAS), Index Copernicus, EBSCOhost Research Databeses, , Türkiye Citation Index, Turk Medline.SubscriptionsThe Turkish Journal of Neurology is delivered complimentarily to the members of Turkish Neurological Society and other scientists and physicians interested in neurology. Tables of contents, abstracts and full texts of all articles published are accessible free of charge through the web site www.tjn.org.tr since 2004. For subscriptions, please contact the Turkish Neurological Society. Address: Turkish Neurological Society Meşrutiyet Caddesi, No: 48/7, 06650 Ankara, Turkey Phone : +90 312 435 59 92 Fax : +90 312 431 60 90 E-mail : [email protected] Web : www.noroloji.org.tr Permission RequestsManuscripts, figures and tables published in the Turkish Journal of Neurology may not be reproduced, archieved in a retrieval system, or used for advertising purposes without a prior written permission from the Turkish Neurological Society. Quotations may be used in scientific articles with proper referral. Advertisement ApplicationsGalenos Publishing HouseMolla Gürani Mah. Kaçamak Sk. No: 21, 34093 F›nd›kzade-‹stanbul-Türkiye Phone : +90 212 621 99 25 Fax : +90 212 621 99 27 [email protected] - www.galenos.com.trIntructions for AuthorsIntructions for authors are published in the journal and are accessible via www.tjn.org.trMaterial DisclaimerScientific and legal responsibilities pertaining to the papers belong to the authors. Contents of the manuscripts and accuracy of references are also the author’s responsibility. The Turkish Neurological Society, the Editor, the Editorial Board or the publisher do not accept any responsibility for the articles.

The journal is printed on acid-free paper.

AIM AND SCOPE

Journal ofTurkish

Neurology

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1. Turkish Journal of Neurology is a periodical journal of the Turkish Neurological Society and is published quarterly.

2. The publishing languages are Turkish and English. All manuscripts should comply with the Turkish Language Institution dictionary and the Turkish Language Writing Guide book (http://tdk.org.tr). Anatomic terminology should be based on Latin nomenclature. Medical terms, in daily use, should be written according to Turkish spelling rules. The words required to be written in their original language by the author are written within quotation marks.

3. All manuscripts should comply with “Uniform Requirements for Manuscripts Submitted to Biomedical Journals” produced and updated by the International Committee of Medical Journals Editors (www.icmje.org).

4. Turkish Journal of Neurology executes compliance with the Declaration of Helsinki Principles (http://www.wma.net/en/30publications/10policies/ b3/index.html). All manuscripts concerning human subjects must contain a statement in the “Materials and Methods/Patients and Methods” section, indicating that the study was approved by the Institutional Review Board. There should also be a statement of declaration about informed consent obtained from research subjects, and it should be placed in the “Materials and Methods/Patients and Methods” section. All manuscripts dealing with animal subjects must contain a statement indicating that the study was performed according to “The Guide for the Care and Use of Laboratory Animals” (www.nap.edu/catalog/5140.html) with the approval of the Institutional Review Board, in the “Materials and Methods” section. The Editor may ask for a copy of the approval document.

5. The editor has the right to reject, to require additional revision or to revise the format of manuscripts which do not follow the rules.

6. Submitted papers are reviewed by the editor, the editorial board, and at least two reviewers. The editor and editorial board may decide to send the manuscript to another reviewer. The editor and editorial board is the complete authority regarding reviewer selection. The reviewers are mainly selected from an International Advisory Board. The editorial board may decide to send the manuscript to independent national or international reviewers according to the subject.

7. The dates of received and accepted of the manuscript are stated in the end of the manuscript when published in the journal.

8. Manuscript submission should be done online (www.tjn.org.tr). The manuscript text should be written in Verdana font, 10 point-type, double-spaced with 2 cm margins on the left and right sides. The article should be prepared in IBM compatible programs (Microsoft Windows, Word 98). The pages should be arranged in numerical order beginning from the initial page, and the numbers should be at the bottom right corner of every page. The main text should not contain any information regarding author(s)’s name and affiliation.

9. The author and the co-authors should sign a cover letter declaring acception of full responsibility for the accuracy of all contents in accordance with the order of authors. They should also declare that the manuscript is an original work that has not been previously published, and is not currently submitted to any other publication. The cover letter should include contributions and responsibilities of each author, and whether there is a conflict of interest regarding manuscript. If there is no conflict of interest it should also be stated. In case of any financial contributions, the sponsors should also be denoted in a cover letter. The cover letter may be sent by fax to +90 312 431 60 90 or its scanned copy may be sent by e-mail ([email protected]) concurrently with manuscript submission.

10. All the entities that provide contribution to the technical content, data collection and analysis, writing, revision etc. of the manuscript and yet do not meet the criteria to be an author should be mentioned in the acknowledgement part.

11. Abbreviations should be internationally accepted and should be defined

accordingly in the text in parenthesis when first mentioned and used in the text.

12. Title page of the manuscript should include Title (Turkish and English), running title (Turkish and English, not more than 40 characters including spaces, Author(s), Institution(s) and Address for Correspondence with e-mail address, fax and phone numbers. Authors should indicate on this page whether the study has been presented previously as an abstract in any congress or symposium.

13. Abstracts should be prepared in Turkish and English for all manuscript except “Letters to the Editor” and “Images in Clinical Neurology”. Abbreviations should be avoided in abstracts. References, tables and citations should not be used.

14. At the end of the abstract, at least 3, at most 5 keywords in both languages are included. Keywords must be written in appropriate quality and standard terminology. Turkish keywords should be chosen from among “Turkey Science Terms”. The authors use information web address for http://www.bilimterimleri.com. “Turkey Science Terms” correspond to the MeSH (Medical Subject Headings). English keywords should be taken from those recommended by the US National Library of Medicine’s headings (MeSH) browser list (http://www.nlm.nih.gov/mesh/MBrowser.html).

15. Research Articles should include; Title, structured abstract (Objective, Materials and Methods/Patients and Methods, Results and Conclusion, limited to 300 words), and key words in Turkish and English, Introduction, Materials and Methods/Patients and Methods, Results, Discussion, Study Limitations, Conclusion, Acknowledgement, and References. Research articles should not exceed 5000 words and 40 references.

16. Editor’s approval is required before submitting a review article since reviews to be published are planned by the Editor.

17. The reviews should include; Title, unstructured abstract and key words in Turkish and English and the main text section. Limit the abstract to 300 words. The number of references should not exceed 40.

18. Case reports should include; Title, abstract and key words in Turkish and English, Introduction, Case, Discussion, Study limitations, Conclusion, Acknowledgment, and References. The sections should be written short excluding the case and an unstructured abstract should be prepared as one paragraph in Case reports. The number of references should not exceed 20.

19. Concise independent reports representing a significant contribution in the related field may be submitted as a Short Communication. The maximum length of a Short Communication is 1500 words. Short communications should include title, an unstructured paragraph of abstract and 2-5 key words in Turkish and English. The main text should include a maximum of one figure and two tables. Number of references should not exceed 10.

20. The letters to the Editor is for letters that are addressing issues or exchanging views on topics arising from published articles. It should not exceed 1000 words and not include an abstract. The number of references should not exceed 10.

22. Figures and tables should be numbered according to the sequence of referral within the text. Each item should be cited in text.

23. Each table should be prepared with double spacing on a separate page. Tables should have a brief title. Authors should place explanatory matter in footnotes not in the heading. Explanations should be made for all nonstandard abbreviations in footnotes. The following symbols should be used for abbreviations, in sequence: *,†,‡,§,||,¶,**,††,‡‡. Each table should be cited in text.

24. Figures should be either professionally drawn or photographed, and these items submitted as photographic-quality digital images. Electronic files of figures should be sent in a format (for example, JPEG or GIF) that will produce high-quality images in the Web version of the journal. Authors should review the images of such files on a computer screen before submitting them to be sure they meet their own quality standards.

INSTRUCTIONS TO THE AUTHORS

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Neurology

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25. X-ray films, scans and other diagnostic images, as well as pictures of pathology specimens should be sent as sharp, glossy, black-and-white or color photographic images, usually in dimensions of 127 x 173 mm. Letters, numbers, and symbols on figures should be clear and consistent throughout, and large enough to remain legible when the figure is reduced for publication. Figures should be made as self-explanatory as possible. For recognizable photographs of human beings, signed releases of the patient or of his/her legal representative should be enclosed; otherwise, patient names or eyes must be blocked out to prevent identification.

26. Type or print out legends for illustrations using double spacing, starting on a separate page, with Arabic numerals corresponding to the illustrations. When symbols, arrows, numbers or letters are used to identify parts of illustrations, identify and explain each one clearly in the legend.

27. When the author(s) has used a figure or table from another source, permission of the author and publisher must be obtained, the necessary printing permission document must be provided and the source referred to in the text.

28. References

- Data and manuscript that have not yet been yet published should not be cited as reference. These should be stated in the main text as “author(s), unpublished data, year”.

- References should be numbered consecutively in the order in which they are mentioned in the text. Identify references in the text, tables and legends at the end of the sentences as superscript. List all authors should be. Journal names should be abbreviated as listed in “Index Medicus” or in “ULAK- BIM/Turkish Medical Index”. Note the following examples:

Journal Articles;

The names of the authors, title of article, abbreviated title of journal, year of publication, numbers of the volume and relevant page numbers of the article.

Wertman E, Zilber N, Abramsky O. An association between MS and type 1 diabetes mellitus. J Neurol 1992;239:43-45.

Supplement;

The names of the authors, title of article, abbreviated title of journal, year of publication, numbers of the volume, numbers of supplement in bracket and relevant page numbers of the article.

Wasylenski DA. The cost of schizophrenia. Can J Psychiatry 1994;39(Suppl 2): 65-69.

Book;

The names of the authors, title of book, numbers of the volume, city, publisher, year of publication.

Ropper AH, Brown RH. Adams and Victor’s Principles of Neurology. 8th ed. New York: McGraw-Hill, 2005.

Book Chapter;

The names of the authors, title of article, editors, title of book, numbers of the volume and issue if existing, city, publisher, year of publication and relevant page numbers of the article.

Pender MP. Multiple sclerosis. In: Pender MP, McCombe PA (eds). Autoimmune Neurological Diseases. 3rd ed. Cambridge: Cambridge University Press, 1995:89-154.

Congress presentation;

The names of the authors, title of presentation, editors (if available), title of

congress book, title of the congress, date of the congress, city, country, publisher, year, relevant page numbers.

Bengtsson S, Solheim BG. Enforcement of data protection, privacy and security in medical informatics. In: Lun KC, Degoulet P, Piemme TE, Reinhoff O, editors. MEDINFO 92. Proceedings of the 7th World Congress on Medical Informatics; 1992 Sep 6-10; Geneva, Switzerland. North-Holland; 1992. p. 1561-1565.

Journal published electronically;

The names of the authors, title of article, abbreviated title of journal, year of publication, numbers of the volume, numbers of the issue in brackets, URL address of the web site, access date.

Morse SS. Factors in the emergence of infectious disease. Emerg Infect Dis 1995;1(1). Available from: URL:http://www/cdc/gov/ncidoc/EID/eid.htm. Accessed date: 25.12.1999.

Web site;

The name of the web site. Accessed date. Available from: Address of the web site.

World Health Organization (WHO). Accessed date: 2008 Jul 9. Available from: http://www.who.int

Thesis;

The names of the authors, title of the thesis, city, university or institution, year. Kanpolat Y. Experimental percutanous access to trigemineal ganglia and hystopathologic evaluation of radiofrequence termic lesion (Associated Professor Thesis). Ankara: Ankara University; 1978.

29. Scientific and legal responsibilities pertaining to the paper belong to the authors. The ideas and recommendations mentioned in the articles and accuracy of references are the responsibility of the authors. The owner of copyright of the accepted manuscript is the Turkish Neurology Society. After acceptance of the manuscript, a copyright transfer form is sent to the author of correspondence by e-mail and required to be signed and returned by e-mail ([email protected]) or fax (+90 312 431 60 90).

30. There is no royalty payment to the authors.

31. Citation

Turk J Neurol

32. Publication rights

Publication rights of Instructions to Authors of Turkish Journal of Neurology belong to the Galenos Yayinevi and the Turkish Neurological Society (All rights reserved).

Manuscripts, figures and tables published in the Turkish Journal of Neurology may not be reproduced, archived in a retrieval system or used for advertising purposes without the prior written permission from the Turkish Neurological Society. Quotations may be used in scientific articles but they must be referred. The content of the advertisements published belong to the related company. All contents are available free of charge without restrictions from the journal’s website at: www.tjn.org.tr

ContactMurat Kürtüncü (Editor)İstanbul University, Faculty of MedicineDepartment of Neurologyİstanbul, 34093, TurkeyE-mail: [email protected]


Journal ofTurkish

Neurology

A-V

Perspectives Neurologists may Perform Interventional Neuroangiography Reha Tolun

Diagnostic and Interventional Neuroradiology: Who Should Do and How? Civan Işlak

Reviews

The Relationship between Migraine and Nutrition Ayçıl Özturan, Nevin Şanlıer, Özlem Coşkun

Intraoperative Neuromonitoring Kubilay Varlı

Research Articles

Correlation of Electromyography and Magnetic Resonance Imaging Findings in the Diagnosis of Suspected Radiculopathy Yıldız Arslan, Ebru Yaşar, Yaşar Zorlu

Investigation of Magnetic Resonance Spectroscopy Findings in Patients with Absence Status Epilepticus Zeynep Aydın Özemir, Betül Baykan, Ebru Nur Vanlı Yavuz, Serra Sencer

Investigation of Patients with Hippocampal Sclerosis Associated with Unusual Epileptic Activities Ebru Nur Vanlı Yavuz, Hakan Yener, Zeynep Aydın Özemir, Nerses Bebek, Candan Gürses, Ayşen Gökyiğit, Betül Baykan

Hyperemesis Gravidarum and Cerebral Electrophysiology Determination of Cerebral Localization through Electroencephalography Signal Processing Hakan Ahmet Ekmekçi, Arzu Setenay Yılmaz, Muhammet Üsame Öziç, Yüksel Özbay, Özlem Seçil Kerimoğlu, Çetin Çelik, Şerefnur Öztürk

Case Reports

Hemichorea and Hemiballismus Associated with Cerebral Vascular Malformation Induced by Hyperglycemia: Case Report Ferda Selçuk, Mine Hayriye Sorgun, Süha Akpınar

Progressive Myoclonic Epilepsy and NEU1 Mutation: A Different Phenotypic Case Ebru Nur Vanlı Yavuz, Güneş Altıokka, Zeliha Matur, Mikko Muona, Nerses Bebek, Candan Gürses, Anna Elina Lehesjoki, Ayşen Gökyiğit, Betül Baykan

Images in Clinical Neurology

A Case of Neuromyelitis Optica Presenting with Intractable Hiccups and Vomiting: Area Postrema Syndrome Derya Kaya, Egemen İdiman, Fethi İdiman, Onur Bulut, Nuri Karabay

Cystic Lesions in Spinal Astrocytoma Ahmet Evlice, Dilek İşcan, Meltem Demirkıran

CONTENTS

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Neurology

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Journal ofTurkish

Neurology

Intracranial Hematoma in Herpes Simplex Encephalitis: A Rare Complication Özlem Ethemoğlu, Mehmet Fırat, Kadri Burak Ethemoğlu, Mehtap Kocatürk

Frontiers in Neurology An Approved Treatment in Periodic Paralyses: Diclorphenamide Mine Sezgin

Does Clopidogrel have an Effect on Migraine Attacks that Emerge after Closure of Atrial Septal Defects? Halil İbrahim Akçay, Murat Kürtüncü

Meeting Highlights

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Perspective / Bakış AçısıDO I:10.4274/tnd.04378Turk J Neurol 2016;22:40-41

Neurologists may Perform Interventional NeuroangiographyNörologlar Girişimsel Nöroanjiyografi Yapabilmelidir

Reha TolunMemorial Hizmet Hospital, Clinic of Neurology, Acute Stroke Treatment Unit, İstanbul, Turkey

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Ad dress for Cor res pon den ce/Ya z›fl ma Ad re si: Reha Tolun MD, Memorial Hizmet Hospital, Clinic of Neurology, Acute Stroke Treatment Unit, İstanbul, Turkey Phone: +90 532 311 33 73 E-mail: [email protected]

Re cei ved/Ge lifl Ta ri hi: 23.03.2016 Ac cep ted/Ka bul Ta ri hi: 11.04.2016

Neurologists may Perform Interventional Neuroangiography

Definitely “Yes”. The base of this clear answer is very reliable. The year 2015 witnessed an important improvement in medicine. Owing to the results of 7 randomized trials published in 2015, endovascular recanalization (thrombectomy/thromboaspiration) became the standard treatment of acute ischemic stroke due to large vessel occlusion with level of class IA evidence. As a result of this improvement, the consensus document of 12 international multi-disciplinary neurointerventional societies, which contains training guidelines who would treat patients with acute ischemic stroke, was published in 8 international journals simultaneously (1). A need for well-trained neurointerventionalists to perform acute ischemic stroke treatment in an organized and efficient team, is cited in the article. A neuroscience background and dedicated neurointerventional training are critical to ensure the best possible patient outcomes.

Recently, a meta-analysis showed that most thrombectomy procedures are performed by experienced neurointerventionalists, including interventional neuroradiologists, endovascular neurosurgeons or interventional neurologists in patients with acute ischemic stroke (2). Existence of vascular neurology specialists and neuro-critical care units are reported to be associated with better patient outcomes.

The answer “Yes” can be supported with another point of view. An analogy can be made between an interventional neurologist and an interventional cardiologist. A cardiologist can perform echocardiography, give medical treatment, monitor patients, and perform angiography if necessary. It would be reasonable if a neurologist did similar treatments. Acute ischemic stroke is a complex disorder. A successful endovascular treatment is based on

quick and comprehensive integration of patient’s anamnesis, clinical and neuroradiological findings. For a good outcome, appropriate patient selection and interventional specialization are required. As a consequence, formal training for both clinical neuroscience and interventional neuroradiology are required. According to the consensus document mentioned above, neuroradiologists, neurologists, and neurosurgeons can be specialized in interventional neurology for endovascular treatment of acute ischemic stroke. The duration of training is two years. The first year of training includes clinical neuroscience and neuroimaging. The second year includes interventional neuroradiology based on endovascular treatment of ischemic stroke under the supervision of a competent interventional neuroradiologist, interventional neurologist or endovascular neurosurgeon in a high volume center. Those who were trained for clinical neuroscience, diagnostic neuroradiology, and neuroangiogiaphy during their specialization do not need to take the first year of the training. These remarkable recent improvements indicate that neurologists who were trained well, can perform interventional neuroangiography.

As an interventional neurologist who began to study catheter-based cerebral angiography 45 years ago and became the pioneer of interventional neuroangiography in Turkey in the 1980s after getting trained abroad, I'm sure you'll anticipate the level of happiness I have, when I see these improvements. But I have a concern that I want to mention. In this “interventional neuroangiography” field, neurologists have to compete against interventional neuroradiologists and endovascular neurosurgeons by means of knowledge, experience and capability and I fear that neurologists may fall behind. But this competition should not be for grabbing a place in this field. They should work as a team. I think, a vascular neurologist (also can be an interventional neurologist) and an interventionalist (neuroradiologist,

Turk J Neurol 2016;22:40-41Reha Tolun; Neurologists may Perform Interventional Neuroangiography

neurosurgeon or neurologist) should get involved in a process of endovascular treatment of a patient with acute ischemic stroke. An interventional neurologist is mainly a vascular neurologist and has the advantage of having a better clinical neuroscience background. In contrast, interventional neurologists have less experience and capability in manual manipulation compared with the other two disciplines, which is a disadvantage. Therefore, depending on the center in which they are trained, the duration of interventional neuroangiography training could last longer than 12 months. With the requests of some young neurologists who are interested in neuroangiography, the “Neuroradiology Scientific Working Group” was founded by the Turkish Society of Neurology (TND) in January 2009 and was selected as a moderator. The name was then changed to the “Interventional Neurology Scientific Working Group”. The TND Cerebrovascular Diseases Scientific Working Group, the TND Neuro-Critical Care Scientific Working Group, and the Turkish Cerebrovascular Diseases Society offered a “Vascular Neurology Sub-branch Speciality”, which lasts 3 years and includes interventional neuroangiography. This offer was delivered to the Ministry of Health by the two societies. These societies exported “Vascular Neurology Physician Certificates” to the experienced neurologists who could give the vascular neurology training. Considering the fact that the proposal given to the Ministry of Medicine will not result in the near term, the TND Interventional Neurology Scientific Working Group specified the training criteria for “Diagnostic Neuroangiography” and “Interventional Neuroangiography” and released them on the TND’s web site. These criteria were revised in consideration

of the consensus document of international multi-disciplinary neurointerventional societies. After completing the training for ischemic stroke treatment, interventional neurologists can also perform cervico-cerebral stent/angioplasty (especially carotid), in addition to thrombectomy/thromboaspiration. After taking extra training, an interventional neurologist can even treat aneursyms, arterio-venous malformations, and perform tumor embolizations. The path of training for “Interventional Neurology” was opened clearly in the world in 2016. In Turkey, the seeds of “Interventional Neurology” were sown in 2009.

I want to end this article by highlighting the fact that neuroendovascular interventions, which can have a high risk of morbidity and complication, should be performed by experienced physicians who were trained by competent specialists in appropriate centers.

Ethics

Peer-review: Internal peer-reviewed.

References1. Training guidelines for endovascular ıschemic stroke ıntervention: An

ınternational multi-society consensus document EJMINT editorial, 2016: 1607000288 (18th February 2016). http://ine.sagepub.com/content/early/2016/03/07/1591019916636801.full.pdf

2. Badhiwala JH, Nassiri F, Alhazzani W, Selim MH, Farrokhyar F, Spears J, Kulkarni AV, Singh S, Alqahtani A, Rochwerg B, Alshahrani M, Murty NK, Alhazzani A, Yarascavitch B, Reddy K, Zaidat OO, Almenawer SA. Endovascular thrombectomy for acute ıschemic stroke: A meta-analysis. JAMA 2015;314:1832-1843.

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Perspective / Bakış AçısıDO I:10.4274/tnd.81488Turk J Neurol 2016;22:42-43

Diagnostic and Interventional Neuroradiology: Who Should Do and How?

Tanısal ve Girişimsel Nöroradyoloji: Kimler Nasıl Yapmalı?

Civan Işlakİstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Radyoloji Anabilim Dalı, İstanbul, Türkiye

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Ad dress for Cor res pon den ce/Ya z›fl ma Ad re si: Civan Işlak MD, İstanbul University Cerrahpaşa Faculty of Medicine, Department of Radiology, İstanbul, Turkey Phone: +90 212 414 30 00-22727 E-mail: [email protected]


Diagnostic and Interventional Neuroradiology: Who Should Do and How?

Medicine was divided into different areas in the late 19th and early 20th centuries to manage accumulated information and to present better treatments to patients. Neurological sciences were also affected by this development; neurology emerged from internal medicine and neurosurgery emerged from general surgery. This change occurred worldwide; however, this trend changed in time from method-based specializations (surgery or internal medicine) towards organ-based specializations. Clinical and surgical specializations occurred in different components in specialties such as gastroenterology within surgery, and in specialties such as ophthalmology and otorhinolaryngology. Specialization in neurological sciences evolved in neurology and neurosurgery because its clinical area was very large and its surgery was different from other surgeries. The appearance of very effective diagnostic methods in neurological sciences and the routine use of metabolic and parametric images in addition to morphologic imaging caused the emergence of neuroradiology as a separate subspecialty in neurological sciences. This process became more complex after the second half of the eighties when spectacular developments occurred in endovascular methods for the treatment of neurovascular diseases, and therapeutic neuroradiology started to be used together with diagnostic neuroradiology. This fragmented structure in neurological sciences became more chaotic considering that neurosciences was a basic science located apart from clinical sciences. In continental Europe, neuroradiology developed as a subspecialty of radiology, whereas in North America and Asia therapeutic and diagnostic methods were divided; diagnostic neuroradiology stayed in neurology practice; however, endovascular treatments continued to be between neurosurgery

and radiology in North America and developed as a branch of neurosurgery in Asia. While the process evolved in such directions around the world, in our country diagnostic and interventional (endovascular) neuroradiology developed as a branch of radiology and neuroradiology departments were established in several universities. During this period, angiographic procedures were performed in some neurology clinics but interest in endovascular methods stayed at a low level in the departments of neurosurgery. After endovascular treatments started to be used routinely for the treatment of aneurysms because of several studies such as the International Subarachnoid Aneurysm Trial, interest of neurosurgeons in interventional procedures increased. Currently in our country, diagnostic neuroradiology remains as a branch of radiology. However, the situation is different in interventional neuroradiology. Despite years of hard effort, no legal regulation has been made and therefore interventional procedures at various difficulty levels are performed or attempted by several specialties. The leading position of our country in interventional neuroradiologic procedures has been possible owing to the efforts of radiologists educated in this topic. Currently, one of the two workshops on regarding neuroradiology and neuroendovascular treatments is performed by the neuroradiology society. Several neurology and neurosurgery departments also try to organize such meetings.

After determination of the current status in our country, the question of ‘Who should perform neuroradiologic interventions and how?’ can be answered more clearly. Considering basic ethical principles of medicine, to protect health and to treat existing diseases, the answer ‘neuroradiologic interventions should be performed by doctors who received a formal education on this topic’ is not arguable. Therefore, opposing educations in the form of "see one, do one, and teach one" and the unacceptable risk of

Turk J Neurol 2016;22:42-43Civan Işlak; Diagnostic and Interventional Neuroradiology: Who Should and How?

patients’ health by physicians who were ‘educated’ in this way is a requirement of medical ethics. We can discuss the topic ‘where will this education be given and to whom will it be given?’ after this basic fact is resolved. Like all areas where human beings are present, self-assessment is necessary in medicine to assure the quality of health care and the reliability of the produced knowledge. Thereby doctors who produce healthcare and information together can monitor each other with "checks and balances" and "self-referral," which is an important worldwide problem of medicine can be avoided. If diagnostic and interventional components of neuroradiology and neuroscience components that include clinical (neurology) and surgical (neurosurgery) domains are practiced separately, development of the aforementioned problems will be unavoidable. Considering the basic fact that neuroradiologic procedures should be performed by doctors who received formal education on this topic, an immediate step forward should be to determine doctors from which specialties will receive this

education and for how long the education should last. After these topics are determined, the decision should be made as to whether a separate neuroradiology department should be established or to select a department under which neuroradiology will be located. Doctors that come from different specialties to neuroradiology should cut relations with their original departments and work solely in the neuroradiology department. As a last word, being a neurologist, neurosurgeon or radiologist is not sufficient to perform interventional neuroradiology. Education is necessary to avoid the malpractices we frequently come across within our country, and performance of neurological interventions by physicians who have had no formal interventional neuroradiologic education should be banned.

Ethics


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Review / DerlemeDO I:10.4274/tnd.37132 Turk J Neurol 2016;22:44-50

The Relationship Between Migraine and NutritionMigren ve Beslenme İlişkisi

Ayçıl Özturan1, Nevin Şanlıer1, Özlem Coşkun2

1Gazi University Faculty of Health Science, Division of Nutrition and Dietetics, Ankara, Turkey2Gazi University Faculty of Medicine, Department of Neurology, Ankara, Turkey

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Ad dress for Cor res pon den ce/Ya z›fl ma Ad re si: Nevin Şanlıer MD, Gazi University Faculty of Health Science, Division of Nutrition and Dietetics, Ankara, Turkey Phone: +90 312 216 26 01 E-mail: [email protected]


Migraine is a kind of headache accompanied by neurologic, gastrointestinal, and autonomous variations. The roles of factors that trigger migraine, especially nutrition triggers, have become much more questionable with the increase in the rate of migraine occurrence. Some patients with migraine have stated that their headache attacks start without any reason. However, inner triggers such as hormonal changes or external triggers such as air exchange, some smells or the association of both triggers can start the headache. Each patient may not have same sensitivity to these triggers. A single factor might become prominent in some patients, but more than one factor may need to be required in other patients. Although the connection between migraine and the factors such as stress, environmental factors, chronic diseases, and nutritional and sleep status has been known, their mechanisms are still not clear. Nutritional status and the effects of nutrition play an important role being pain triggers in everybody, especially children and young people who suffer from migraine headache. Considering the migraine triggers generally, it has been suggested in studies that there is at least one nutrition-related trigger and hunger is the most frequently reported trigger in terms of diet. Moreover it is known that chocolate, tea, coffee, cheese, and alcohol may trigger migraine because of some specific elements within them. In recently conducted studies, using some functional foods have raised on the treatment of migraine. For this reason, the relationship between migraine and triggering factors as food and nutrition are examined in this study.

Keywords: Migraine disorders, food, nutritional status

Migren, binlerce yıldan beri bilinen bir hastalık olup nörolojik, gastrointestinal ve otonom değişikliklerin eşlik ettiği bir baş ağrısıdır. Migrenin görülme sıklığının artmasıyla birlikte migren tetikleyici faktörlerin rolü ve özellikle tetikleyici besinler daha fazla tartışılır hale gelmiştir. Bazı migrenli hastalar baş ağrısı ataklarının nedensiz bir şekilde başladığını ifade etmektedirler. Ancak çoğunlukla hormonal değişimler gibi içsel ya da hava değişimi, bazı kokular vs. gibi bir dışsal tetikleyici ya da tetikleyicilerin birlikteliği ağrıyı başlatabilmektedir. Her hasta bu tetikleyicilere karşı aynı duyarlılıkta olmayabilir. Bazılarında tek bir faktör öne çıkarken, bazılarında da birkaç faktörü birden ele almak gerekebilmektedir. Stres, çevresel faktörler, kronik hastalıklar, uyku ve beslenme durumu gibi etkenlerin migren ile ilişkisi bilinmekle birlikte bu etkenlerin mekanizmaları hala net değildir. Çocuklar ve gençler başta olmak üzere migren tipi baş ağrısı çeken herkeste ağrıyı tetikleyici olarak beslenme durumu ve besinlerin etkisi önemli yer tutmaktadır. Genel olarak migren tetikleyicileri düşünüldüğünde yapılan çalışmalarda en az bir beslenme kaynaklı tetikleyici öne sürülmekte, diyet açısından en sık bildirilen tetikleyicinin açlık olduğu söylenmektedir. Çikolata, çay, kahve, peynir, alkolün ise içerdiği bazı spesifik öğeler sebebiyle migrende tetikleyici özellik gösterdiği belirtilmektedir. Yapılan yeni çalışmalarda migren tedavisinde ek olarak bazı fonksiyonel besinlerin kullanımı da gündeme gelmiştir. Bu nedenle, çalışmada migrenin tetikleyici faktörlerinden besin ve beslenme ile ilişkisi irdelenmiştir.

Anahtar Kelimeler: Migren hastalıkları, besin, beslenme durumu

Sum mary

Öz

Turk J Neurol 2016;22:44-50Özturan et. al.; The Relationship Between Migraine and Nutrition

Introduction

Migraine is a primary, episodic disorder in which different combinations of neurologic, gastrointestinal, and autonomic alterations accompany (1). Migraine affects 240 million people worldwide who are affected by approximately 1.4 billion migraine attacks each year (2). Migraine frequency in women is known to be twice that of men during the menstrual period and migraine attacks are more severe (3); a study from İstanbul detected the beginning age of migraine in women to be 22.7 years (4). Migraine is not a single symptom or a problem that occurs at a single location. Also, it does not always present with a similar pattern, instead it may sometimes be progressive (5) and it is diagnosed based on patient’s history. Causative factors should be considered for the first headache but migraine classifications should be considered when pain becomes chronic (6). Typical features of migraine are headache that may last for 4-72 hours, generally unilateral, which may be moderate or severe in severity and tends to recur. Its severity generally increases with physical activity, nausea, and sensitivity against light and noise occur (7,8). A study found the most common symptoms were noise sensitivity (91.3%) and nausea (74.8%). The same study also investigated triggers and found that stress (81%) and noise (54.5%) were the most frequent triggers although hunger (37.2%) and certain foods (5.9%) were also among the triggers (4). There is a complex relationship between migraine and nutrition. Food can affect nervous pathways, which produces pain through the vasoconstrictor or vasodilator properties of their ingredients (9,10). Although there are acute and preventive treatments for migraine, nutrition still seems to be an important component. For the evaluation of migraine patients, food consumption is investigated and the patient is asked to keep a migraine diary to identify food that caused the attack. Studies revealed at least one trigger stemming from nutrition and the common triggers were skipping meal, caffeine, dairy products, alcoholic beverages, fermented food, and chocolate (9,11). Fasting is generally seen as an important trigger and alcohol intake is important, especially for younger patients (9,12). Cheese, chocolate and red wine that include these chemicals are also important triggers of migraine because tyramine, phenylethylamine, and histamine are believed to play roles in the mechanisms that trigger headache (13). In recent years, functional nutrients are believed to be effective in the prevention and treatment of migraine. Although studies are limited, magnesium, riboflavin, coenzyme Q, coltsfoot and chrysanthemum are known to have beneficial effects (11,14). Magnesium and chrysanthemum affect serotonin receptor activity, coenzyme Q and riboflavin affect oxidative metabolism, and coltsfoot have anti-inflammatory effects and therefore they play roles in migraine development (14). Additionally, although elimination diets are recommended in migraine treatment and the effects of this treatment are known to be based on the migraine triggering effect of food allergy, the role of mechanisms associated with immunoglobulin (Ig) IgE and IgG are still controversial (10,15).

Trigger Factors

Some patients with migraine patients state that their headaches begin without any apparent cause. However, in most occasions,

endogenous factors such as hormonal changes and exogenous changes such as weather factors or some odors may initiate headaches. Every migraine patient may not be at same sensitivity level to these factors. A single trigger may initiate pain in some of these patients but several factors are needed to initiate pain in others. Migraine is frequently triggered by stress, menstruation, insufficient or excessive sleep, weather changes (humidity, wind, atmospheric pressure), missing a meal, alcohol (especially wine and beer), odor (perfume or chemical with sharp odors), bright lights, cigarette smoke, high altitude, cough, or some food (16). The most common food triggers are alcohol, chocolate, cheese, caffeine, monosodium glutamate, and aspartame (11). In addition to environmental factors, personal problems or chronic diseases, premenstrual syndrome, pregnancy, hypertension, or obesity may be causes or triggers of pain (17,18,19,20). A study in patients with and without aura (n=182) detected stress (94.5%), meal skipping (89%), noise (87.9%), insufficient sleep period (87.4%), fatigue (86.3%), bright light (79.1%), menstruation (77.3%), sharp odor (69.2%), and weather conditions (65.4%) were detected to triggered migraine and food triggers were found to be the cause in 79.1% of the patients. In addition, this study suggested that females were more sensitive to food triggers. The brain regions affected by migraine triggers may vary between the sexes because of differences in neurotransmitter concentrations, receptor sensitivity, or hormonal interactions (21).

Migraine in the Presence of Insulin Resistance and Obesity

Insulin sensitivity is known to be impaired and diseases such as hypertension, diabetes, high cholesterol, and obesity are commonly seen in patients with chronic migraine patient. The highest migraine prevalence was found in morbidly obese women (17,20). The association between migraine and obesity has received much attention over the last 10 years. A study evaluated patients who had different types of headache by dividing them into 5 groups according to body mass index (BMI) (lean, normal, overweight, obese, morbidly obese). Study results showed that although migraine prevalence was not affected by BMI, the risk of chronicity of episodic migraine was higher in migraine patients who were obese (20). The first longitudinal study about headache-obesity relationship monitored 1192 patients with episodic headaches or chronic daily headache aged between 18-65 years for 11 months. The transformation of episodic headache to chronic daily headache was found 5 times higher in obese patients compared with non-obese patients (22). Another study found that risk of headache in obese patients compared with patients with normal BMI was 35% higher and 80% higher in morbidly obese patients (23). Additionally, daily headache was associated with obesity and obesity was a stronger risk factor for migraine than tension type headache (20). Obese patients were reported to have 47% more headache or migraine than non-obese patients among 14000 young women aged between 18-23 years (24). A study of 30215 subjects found migraine symptoms in 3791; there was no association between migraine prevalence and increased BMI but an association was found between increased body weight with increased headache incidence and pain severity (25). A recent study in similar age groups found a relationship between migraine and

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Turk J Neurol 2016;22:44-50 Özturan et. al.; The Relationship Between Migraine and Nutrition

obesity (26,27). Several adipocytokines are released from adipose tissue. Adiponectin is one of the adipocytokines. Adipokines have inflammatory properties and they may aggravate inflammatory disorders. A study on this topic in female patiens with migraine evaluated adiponectin and oligomer levels before and after an unsuccessful acute treatment; adipokine levels significantly decreased after treatment and this suggested an association between adipokines and migraine (28). However, the relationship between migraine and obesity and the role of adipokines in this relation is still far from exact. Leptin is an adipocyte hormone that is an important regulator of food intake and energy homeostasis. Regulated leptin levels help to prevent obesity. The leptin levels of 61 patients with episodic migraine and 64 controls were not different between patients with migraine and controls according to BMI. Adipose tissue mass and percentage were significantly lower in patients with migraine. In conclusion, low leptin levels and adipose tissue mass were related with migraine pathogenesis (29). Although studies about the relationship between metabolic syndrome and migraine are limited, 11.3 years of follow-up of 19895 subjects showed an association between migraine and increased risk of metabolic syndrome (30). Gozke et al. (31) investigated the association between tension-type headache and migraine with metabolic syndrome parameters and concluded that patients should be monitored for hypertension and hyperlipidemia especially, but no data were found to support a higher presence of metabolic syndrome in different types of headache. Another study in 210 patients with metabolic syndrome showed that migraine accompanied the metabolic syndrome in 19.5% of the patients. The results of the study demonstrated that increased waist circumference, obesity, and impaired glucose metabolism, which are components of metabolic syndrome, were more frequent in patients with migraine. Insulin resistance was suggested to be responsible for high migraine prevalence because it is common in the pathogenesis of these disorders (32). A study evaluated 83 patients with episodic migraine patients, 83 patients with chronic migraine, and 83 healthy individuals, and BMI, waist circumference, and blood pressure measurements were performed. In addition, fasting glucose, 2-hour oral glucose tolerance test with 75 g glucose, serum HbA1c, blood lipid profile, C-reactive protein, and prolactin levels were measured. There was a significant association between insulin resistance and migraine and the patients with chronic migraine patients had 3 times more insulin resistance compared with patients with episodic migraine. However, considering migraine risk, the comorbidity of obesity and insulin resistance was riskier than insulin resistance alone (17). In recent years, several orexigenic and anorexigenic peptides that are released from hypothalamus have been believed to have roles in the pathogenesis of migraine and obesity. Hypothalamic symptoms such as increased appetite, disturbance in mood and sleep, and postdromal symptoms in migraine were associated with this condition. Also hypothalamic disturbance may cause hyperphagia and increased body weight. In addition, hypothalamic peptides and nutrition-related neurotransmitters such as orexin and adipokines may contribute to the pathophysiology of migraine. Regulation of the release of these peptides and proteins may trigger or contribute to the development of headache in migraine (26).

Association with Nutrition

Food TriggersNutrition and food status are very important triggers of

pain especially in children and adolescents (9). Fasting, alcohol, chocolate, and cheese are the most commonly reported triggers (Table 1) (10). Generally, at least one nutritional trigger is found in studies that evaluated migraine triggers and the most commonly reported trigger was fasting, followed by chocolate and alcohol (12) alcohol intake is a potential cause of recurrent headache in teenagers (9). Patients with migraine may sometimes be very sensitive to one or more food components and this may be associated with food intolerance. A skin test for food allergy is a commonly used method to test for intolerance. The main chemicals that were proposed to trigger headache include monosodium glutamate, nitrate, nitrite, tyramine, phenylethylamine, and other amines including histamine. Tyramine is found especially in cheese like cheddar, phenylethylamine is found in chocolate, octopamine is found in citrus fruits, and histamine is found in red wine and beer. Caffeine dependence and excessive coffee consumption are also associated with throbbing headache and migraine. Fasting and missing meals may also be factors that cause relapse of pain in patients with migraine (11,13). Alcohol consumption may not be tolerated in some patients with headache and it may be an important trigger; therefore, patients are recommended to avoid alcohol (33). Sodium nitrite, which is generally used for food coloring and prevention of botulism may cause headache in some patients and this effect may be due to nitric oxide release and the resulting vasodilatation. Therefore, subjects who are sensitive to these nutrients are recommended to avoid them (11).

Food triggers may exert their effects by mediating serotonin and norepinephrine release, causing vasoconstriction or by directly stimulating brain-stem and cortical nervous pathways. In this case treatment can be initiated by omitting food triggers from the diet (9).

AlcoholAlthough alcoholic beverages are known to trigger headache,

the type of beverage is also important for the development of pain (8,34,35). Although not exactly known the mechanism through which alcohol triggers migraine may be associated with ethanol, biogenic amines (histamine, tyramine, phenylethylamine, or others), sulfides, phenolic flavonoids, serotonin release from thrombocytes, or dehydration (33,34). Red wine in particular is

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Table 1. The most commonly reported nutritional triggers (10)Chocolate

Citrus fruits

Diary products (yoghurt, cheese)

Fatty and fried food

Tea, coffee, cola

Aspartame

Alcoholic beverages

Food colorings


shown as an example for triggering migraine among alcoholic beverages even individuals without migraine may develop headache after red wine consumption. Mechanism is believed to be associated with phenolic flavonoid radicals and tannin but because white wine may be even more effective in development of headache than red wine a consensus cannot be reached over red wine (33,35). On the other hand, red wine, whisky, and dark-colored alcoholic beverages are natural by products of alcoholic fermentation and include same-type substances. They cause more morning headaches when compared with clear alcoholic beverages like gin or vodka (11). An association has been proposed between alcohol and migraine. Therefore, due to the trigger effects of some of its ingredients red wine should not be consumed by patients with migraine.

Chocolate Chocolate is believed to induce migraine because of its

ingredients like theobromine, caffeine, and biogenic amines such as phenylethylamine (34,36). Twenty percent of the patients in a study considered chocolate to be a headache trigger (34). However, a study on 63 women with chronic headache found that chocolate had no migraine or headache triggering effect (37). The effect of chocolate can be better understood with a diet diary because studies on migraine and chocolate may give conflicting results. Individuals whose headaches are believed to be triggered by chocolate may limit its use or totally avoid it.

Cheese Cheese has been suggested to induce migraine because

it includes biogenic amines especially tyramine (13,34). An evaluation of nutrients that trigger migraine revealed that 0-19% of patients reported that cheese triggered their migraine or headache attacks (34). Although biogenic amines inside cheese are considered separately among migraine inducers, cheese consumption should also be limited because there are reports that relate cheese consumption with migraine attacks.

Biogenic AminesBiogenic amines like histamine, tyramine, phenylethylamine,

putrescine, cadaverine, and spermidine which are found in several foods play important roles in human metabolism. Histamine, tyramine, and phenylethylamine are especially associated with migraine and headache (36). Intravascular and subcutaneous administration and inhalation of histamine were shown to cause headache. However there are insufficient studies to support this hypothesis (7). A study on patients with cluster-type headache and migraine found increased plasma levels of biogenic amines (especially tyramine, octopamine, and synephrine). Therefore, more research is warranted to determine the role of biogenic amines in headache (38). Although some biogenic amines have been associated with headache, no studies to date have provided an evidence base.

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Table 2. Effects of functional nutrients on migraine (14)

Functional nutrients Effect on migraine Magnesium Neuro-inflammatory blockage

Calcium channel blocking effectNMDA receptor blockage, NO synthesis, release and activitySerotonin receptor affinity and activity Endogenous hormone regulation plays role in vascular and neural processes

Riboflavin Riboflavin is important because it is a major cofactor in oxidative metabolism and mitochondrial energy production. Riboflavin metabolism in the brain may affect migraine pathophysiology through several mechanismsMigraine was defined as a defect in oxidative metabolism in the brain. Mitochondrial dysfunction in migraine is related with low mitochondrial riboflavin levels and it has a potential role in increasing mitochondrial energy productivityRiboflavin is known to have important roles in controlling cardiovascular risk in patients with migraine with aura

Coenzyme Q10 CoQ10 plays a central role in electron transport and energy metabolismConsidering its critical function in mitochondria, and its protective role in stabilization of endothelial function which stimulates release of lipoproteins and NO, CoQ10 may be important in the pathophysiology of migraineDisturbance of mitochondrial oxidative metabolism may play an important role in the pathophysiology of migraine because it has a role in neural information processing. Therefore, CoQ10 may be therapeutically important in migraine

Butterbur Butterbur, is believed to have analgesic effects by causing anti-inflammatory inhibition of leukotriene biosynthesis and also regulates calcium channels. Both actions are important for their effect on migraine

Chrysanthemum (feverfew)

Chrysanthemum (feverfew) probably exerts its anti-migraine effects by its bioactive ingredient sesquiterpene, which is parthenolide lactone and has a lactone structure. In addition, chrysanthemum also includes melatonin which casts doubt on whether the parthenolide is its major active ingredient. Parthenolides are known to inhibit prostaglandins that transmit pain, inhibit serotonin which induces migraine, and decreases platelet production in capillaries

NMDA: N-Methyl-D-aspartate, NO: Nitric oxide, CoQ10: Coenzyme Q10


CaffeineCaffeine is commonly found in chocolate, tea, coffee and cola

which are parts of our everyday diet. Caffeine causes vasoconstriction and release of stimulating neurotransmitters and stimulates adenosine receptors inside the brain and vessels and blocks their inhibitors (11). A study in young adults and adolescents who had excessive amounts of tea and coffee intake showed an association between coffee consumption and migraine (8). In addition, in the 2nd edition of the International Classification of Headache Disorders 2 (item; 8.4.1) if caffeine intake in 2 weeks is equal to or more than 200 mg, abrupt cessation of caffeine may also have a triggering effect (39). Caffeine may be important in headache mechanisms because it is known for its stimulating effects. The exact amount of caffeine that can be associated with headache is not known because these studies generally assess caffeine amount by tea and coffee consumption.

AspartameAspartame is an artificial sweetener that is 150-200 times

sweeter than sucrose. Symptoms associated with aspartame use include neurologic symptoms and migraine. Although migraine induction by aspartame is not certain, 30 mg/kg aspartame intake is the normal daily dosage, and harmful effects are seen when intake reaches 75 mg/kg (34). It is not possible to reach firm conclusions about the mechanism of action and risk level with aspartame because too few studies have assessed the relationship between aspartame and headache; more research is warranted on this topic.

FastingMissing a meal or fasting are common triggers of migraine

in adults (8). Hypoglycemia that accompanies migraine has been suggested to induce migraine. More frequent and smaller meals, and snacks may be suggested as a strategy to prevent headache because such an approach regulates glucose levels. Regular meal times also improve hypoglycemia and may be suggested as a factor in migraine treatment. Although glucose levels have not been evaluated in patients with migraine, nourishment may have a protective effect against headache (40). Although definite results have not been obtained to confirm that fasting-induced hypoglycemia attacks induce migraine this should also be kept in mind. For this reason, snacks should be planned within the diet of patients with migraine; patients should not be without food for long hours.

Functional NutrientsFunctional nutrients are defined as foods that have health

benefits that are used to prevent or treat diseases. The main nutrients used for migraine treatment are shown in Table 2 (14). Although there few studies about the association of functional nutrients with migraine, important results have been obtained. Functional nutrients should be diversified and more research should be performed on this topic.

Lifestyle Arrangements

Preventive TreatmentAlthough 25% of patients with migraine believe that

prevention is necessary, preventive treatment is used by very few patients (1). Pharmacologic treatment of migraine may be acute

to terminate the attack or preventive to protect against the attack. Although preventive treatment is appropriate for many patients with migraine, a decision should be made with consideration of vocational productivity, and social, familial and recreational activities (1,41).

Magnesium Supplementation Magnesium is the second intracellular cation that is important

in many intracellular processes and it plays a very important role in migraine pathogenesis. Magnesium deficiency plays important roles in cortical spreading depression, platelet hyper aggregation, serotonin receptor function, and release of certain neurotransmitters. Magnesium deficiency may develop in patients with migraine due to a genetic defect in magnesium reabsorption, magnesium loss from kidneys, emptying of magnesium stocks due to stress, low dietary intake, or some other reasons. The daily recommendation for magnesium is 400 mg magnesium oxide. If this treatment does not produce the desired effect, dose can be doubled (42).

Nutritional Treatment Considering migraine to be associated with allergy elimination

diets that removed allergic food from the diet were considered. The relationship between migraine and allergy was first proposed by Lesne and Richet in 1913 and migraine was considered an atopic disease for many years. Although many reports have demonstrated that migraine attacks developed due to food allergy, the role of the interaction between migraine and allergy and the role of IgE-mediated allergic mechanisms in pain production are still debated (15). IgE should be considered when considering elimination diets for patients with migraine based on food allergy; specific diets have been shown to reduce migraine attacks. However, the IgG response generally develops more slowly (10). A study that assessed the effectiveness of elimination diets in 30 patients with migraine without aura reported a significant decrease in the number of migraine attacks and days with headache. In this study elimination diets were determined based on IgG antibodies and mainly spices, dried nuts, seafood, starch, and additives were detected to produce IgG-positive responses (43). A study on patients with irritable bowel syndrome and migraine evaluated the effectiveness of elimination diets; the authors reported a decrease in number and duration of attacks and symptoms. This study also evaluated nutrients that produced an IgG response and listed dry fruits, cereals, spices, and several fruits and vegetables (44). Another frequently studied topic has been consumption of functional nutrients. A study that evaluated the association of functional nutrients and other nutrient groups and reported that 400 mg magnesium, butterbur 75 mg twice a day for a month and then 50 mg a day, chrysanthemum 100 mg a day, coenzyme Q10 300 mg a day, riboflavin 400 mg a day, and alpha lipoic acid 600 mg a day may be given (11). Balanced, regulated and diversified food is recommended during pregnancy, which is a risky period for migraine development due to hormonal effects. Fasting and hypoglycemia should be avoided. Limiting chocolate, cheese, and monosodium glutamate intake may help to decrease headaches but due to the benefits of cheese, its limitation during pregnancy may not be appropriate. On the other hand, limitation of alcohol intake and cessation of smoking are also recommended for health reasons. Patients should also try to avoid stressful conditions. Relaxation

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techniques such as breathing exercises also play important roles (45).

Conclusion

In conclusion migraine is known to be a severe neurologic disorder that affects the social lives of individuals. New approaches are being developed for the treatment of migraine which is associated with many variables such as lifestyle, food choice, specific problems of individuals and chronic illnesses. Nutritional regulation forms an important part of environmental and individual factors. Therefore, patients’ avoidance of drug use has popularized the use of functional nutrients, and more research on this topic is needed. Use of a diet diary by patients with migraine associated with nutritional treatment and focusing attention on nutrients that are consumed during attack periods is an important start point. This approach can help to understand how nutrients affect individuals, to decide whether functional nutrients should be included in the treatment, and to decrease attack frequency. The selection of treatment method after considering all factors is important to achieve a better quality of life. Attention should be paid to lifestyle and behavioral changes that could be used to prevent or delay progression of migraine. Main changes include respecting rules of sleep hygiene, performing relaxation and breathing exercises, obeying recommendations for nutritional arrangements, taking an adequate amount of daily fluid, and maintaining a social life.

Ethics

Peer-review: Externally peer-reviewed.

Authorship Contributions

Concept: Ayçıl Özturan, Nevin Şanlıer, Özlem Coşkun, Design: Ayçıl Özturan, Nevin Şanlıer, Özlem Coşkun, Data Collection or Processing: Ayçıl Özturan, Nevin Şanlıer, Özlem Coşkun, Analysis or Interpretation: Ayçıl Özturan, Nevin Şanlıer, Özlem Coşkun, Literature Search: Ayçıl Özturan, Nevin Şanlıer, Özlem Coşkun, Writing: Ayçıl Özturan, Nevin Şanlıer, Özlem Coşkun.

Conflict of Interest: No conflict of interest was declared by the authors.Financial Disclosure: The authors declared that this study has received

no financial support.

References1. Fofi L, Egeo G, Aurilia C, Barbanti P. Migraine prophylaxis: What is new and

what we need? Neurol Sci 2011;32(Suppl 1):111-115.2. Philips P. Mirgaine as a woman’s issue-will research and new treatments

help? JAMA 1998;280:1975-1976.3. Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevelance and

Burden of Migraine in the United States: Data from the American Migraine Study II. Headache 2001;41:646-657.

4. Börü ÜT, Koçer A, Lüleci A, Sur H, Tutkan H, Atlı H. Prevelance and characteristics of migraine in women of reproductive age in İstanbul, Turkey: A Population Based Survey. Tohoku J Exp Med 2005;206:51-59.

5. Taylor RF. Lifestyle changes, dietary restrictions, and nutraceuticals in migraine prevention. Techniques in Regional Anesthesia and Pain Management 2009;13:28-37.

6. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 2013;33:629-808.

7. The International Classification of Headache Disorders 2nd Edition. Cephalalgia 2004;24(suppl 1):1-160.

8. Rockett FC, Oliveira VR, Castro K, Chaves ML, Perla AS, Perry ID. Dietary aspects of migraine trigger factors. Nutrition Reviews 2012;70:337-356.

9. Millichap GJ, Yee MM. The diet factor in pediatric and adolescent migraine. Pediatr Neurol 2003;28:9-15.

10. Finocchi C, Sivori G. Food as trigger and aggravating factor of migraine. NeurolSci 2012;33(Suppl 1):77-80.

11. Sun-Eldestein C, Mauskop A. Foods and supplements in the management of migraine headaches. Clin J Pain 2009;25:446-452.

12. Fukui TP, Gonçalves TRT, Strabelli GC, Lucchino FMN, Matos CF, Santos MPJ, Zukerman E, Zukerman-Guendler V, Mercante JP, Masruha MR, Vieira DS, Peres MFP. Trigger factors in migraine patients. Arq Neuropsiquiatr 2008;66:494-499.

13. Arora H, Rajdeep K. The role of diet in migraine headaches. Delhi Psychiatry Journal 2008;11:69-72.

14. Taylor RF. Nutraceuticals and Headache: The biological basis. American Headache Society 2011;51:484-501.

15. Tan UF, Kalpaklıoğlu AF, Koç SR, Tunçkol M. Migrende IgE Aracılı Allerjinin Rolü. Astım Allerji İmmünoloji 2005;3:10-15.

16. Yaman M, Demirkıran K, Oruç S. Migrende baş ağrısını tetikleyici ve kötüleştirici faktörler. Düzce Tıp Fakültesi Dergisi 2007;9-13.

17. Fava A, Pirritano D, Consoli D, Plastino M, Casalinuovo F, Cristofaro S, Colica C, Ermio C, Bartolo De M, Opipari C, Lanzo R, Consoli A, Bosco D. Chronic migraine in women is associated with insülin resistance: A cross-sectional study. European Journal of Neurology 2014;21:267-272.

18. Göksel KB. Menstrüel Migren ve Tedavisi. Türk Nöroloji Dergisi 2008;14:5-14.19. Bigal ME, Kurth T, Santanello N, Buse D, Golden W, Robbins M, Lipton

RB. Migraine and cardiovascular disease. Neurology 2010;74:628-635.20. Bigal EM, Lipton BR. Obesity is a risk factor for transformed migraine but

not chronic tension-type headache. Neurology 2006;67:252-257.21. Dora B, Yılmaz N, Apaydın-Doğan E, Karahasan-Özdemir C, Türkay M.

Intergender differences in triggering factors among different subtypes of migraine and tension-type headache. Journal of Neurological Sciences 2010;27;386-394.

22. Scher AI, Stewart WF, Ricci JA, Lipton RB. Factors associated with the onset and remission of chronic daily headache in population-based study. Pain 2003;106:81-89.

23. Keith SW, Wang C, Fontaine KR, Cowan CD, Allison DB. BMI and headache among women: Results from 11 epidemiologic datasets. Obesity (Silver Spring)2008;16:377-383.

24. Brown WJ, Mishra G, Kenardy J, Dobson A. Relationships between body mass index and well-being in young Australian women. International Journal of Obesity 2000;24,1360-1368.

25. Bigal ME, Gironda M, Tepper SJ, Feleppa M, Rapoport AM, Sheftell FD, Lipton RB. Headache prevention outcome and body mass index. Cephalagia 2006;66:545-550.

26. Peterlin BL, Rosso AL, Williams MA, Rosenberg JR, Haythornthwaite JA, Merikangas KR, Gottesman RF, Bond DS, He JP, Zonderman AB. Episodic migraine and obesity and the influence of age, race, and sex. Neurology 2013;81,1314-1321.

27. Robberstad L, Dyb G, Hagen K, Stovner LJ, Holmen TL, Zwart JA. An unfavorable lifestyle and recurrent headaches among adolescents: The HUNT study. Neurology 2010;75:712-717.

28. Peterlin BL, Tietjen EG, Gower BA, Ward NT, Tepper JS, White WL, Dash PD, Hammond ER, Haythornthwaite JA. Ictal adiponectin levels in episodic migraineurs: A randomized pilot trial. Headache 2013;53:474-490.

29. Guldiken B, Guldiken S, Demir M, Turgut N, Tuğrul A. Low leptin levels in migraine: a case control study. Headache 2008;48:1103-1107.

30. Winsvold BS, Sandven I, Hagen K, Linde M, Midthjell K, Zwart JA. Migraine, headache and development of metabolic syndrome: An 11-year follow-up in the Nord-Trondelag Health Study (HUNT). Pain 2013;154:1305-1311.

31. Gozke E, Unal M, Engin H, Gurbuzer N. An observational study on the association between migraines and tension type headaches in patients diagnosed with metabolic syndrome. ISRN Neurology 2012, http://dx.doi.org/10.1155/2013/147065

32. Guldiken B, Guldiken S, Taskiran B, Koc G, Turgut N, Kabayel L, Tugrul A. Migraine in metabolic syndrome. Neurologist 2009;15:55-58.

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33. Panconesi A. Alcohol and migraine: Trigger factor, consumption, mechanisms. J Headache Pain 2008;9:19-27.

34. Wöber-Bingol Ç, Wöber C. Triggers of migraine and tension-type headache. Handbook of Clinical Neurology 2011;97:161-172.

35. Krymchantowski VA, Jevoux CC. Wine and headache. Headache 2014;54:1-9.

36. Wöber C, Holzhammer J, Zeitlhofer J, Wessely P, Wöber-Bingöl Ç. Trigger factors of migraine and tension-type headache: Experience and knowledge of the patients. J HeadachePain 2006;7:188-195.

37. Marcus DA, Scharff L, Turk D, Gourley LM. A double-blind provocative study chocolate as a trigger of headache. Cephalalgia 1997;17:855-862.

38. D’Andrea G, Terrazzino S, Leon A, Fortin D, Perini F, Granella F, Bussone G. Elevated levels of circulating traceamines in primary headaches. Neurology 2004;62:1701-1705.

39. http://ihs-classification.org/en/02_klassifikation/03_teil2/08.04.01_substance.html Erişim Tarihi: 30.12.2015

40. Turner PD, Smitherman TA, Penzien BD, Porter AHJ, Martin TV, Houle TT. Nighttime snacking, stress, and migraine activity. Journal of Clinical Neuroscience 2014;21:638-643.

41. Schmitz N, Admiraal-Behloul F, Arkink BE, Kruit MC, Schoonman GG, Ferrari MD, Buchem MA. Attack frequency and disease duration as ındicators for brain damage in migraine. Headache 2008;48:1044-1055.

42. Mauskop A, Varughese J. Why all migraine patients should be treated with magnesium. J Neural Transm 2012;119:575-579.

43. Alpay K, M Ertas, Orhan EK, Üstay DK, Lieners C, Baykan B. Diet restriction in migraine, based on IgG against foods: A clinical double-blind, randomised, cross-over trial. Cephalalgia 2010;30:829-837.

44. Aydinlar EI, Dikmen PY, Tiftikci A, Saruc M, Aksu M, Günsoy HG, Tozun N. IgG-Based Elimination Diet in Migraine Plus Irritable Bowel Syndrome. Headache 2013;53:514-525.

45. Airola G, Allais G, Gabellari IC, Rolando S, Mana O, Benedetto C. Non-pharmacological management of migraine during pregnancy. Neurol Sci 2010;31(Suppl 1):S63-65.

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51

Review / DerlemeDO I:10.4274/tnd.59913Turk J Neurol 2016;22:51-54

Ad dress for Cor res pon den ce/Ya z›fl ma Ad re si: Kubilay Varlı MD, Hacettepe University Faculty of Medicine, Department of Neurology, Ankara, Turkey Phone: +90 312 305 18 06 E-mail: [email protected]


Intraoperative NeuromonitoringAmeliyatta Nörofizyolojik İzleme

Kubilay VarlıHacettepe University Faculty of Medicine, Department of Neurology, Ankara, Turkey

Principal aim of “intraoperative neuromonitoring” (IN) is to prevent the potential neurlogical deficits may caused by surgical process, which is very appropriate to the principal rule of medicine “primum non nocere”. In addition to reducing the neurological deficits, monitoring of the neurological structures, also provides very valuable knowledge about anatomy and physiology of central nervous system. IN become almost routine technique during the surgeries concerned to the central and/or peripheral neurological structures. The used monitoring technique varies according to the involving neurological structure, and the aim of the surgical intervention. Because of this, the stuff who runs the monitoring, must be well trained and experienced. As it similar in the other countries, there are serious controversies on the IN in our country by means of training, price, legal aspects. Before the problems hard to be solve, all the sides of the neuromonitoring must be together to regulate the all aspects of the issue.

Keywords: Intraoperative neuromonitoring, somatosensory evoked potential, motor evoked potential

“Önce zarar verme” ilkesinin, cerrahi girişimlere uygulanması olarak kabul edilebilecek olan, “ameliyatta nörofizyolojik izleme” (ANİ) tekniğinin temel amacı; ameliyatta risk altında olan nörolojik dokuların korunması veya en az hasarla girişimin bitirilmesini sağlamaktır. Bunun yanında ameliyatta izleme, başlangıçtan beri, santral sinir sistemi anatomisi ve fizyolojisinin anlaşılmasında da çok önemli katkılarda bulunmuştur. Son yıllarda merkezi ve periferik sinir sistemini ilgilendiren tüm ameliyatlarda neredeyse rutin uygulamaya giren, ANİ için, girişimin yeri ve hedefine göre değişmek üzere son derece değişik teknikler uygulanmaktadır. Bu nedenle, bu girişimi yapanların son derece eğitimli ve tecrübeli olmaları gerekmektedir. Ülkemizde de son yıllarda uygulamanın yaygınlaşması ile eğitim, uygulama, ücretlendirme ve uygulayıcılar açısından bazı sorunlar ortaya çıkmaktadır. Uygulamanın tüm tarafları bir araya gelerek, sorunlar çözülmez olmadan konu bütün boyutları ile ele alınmalı ve düzenlemeler yapılmalıdır.

Anahtar Kelimeler: İntraoperatif nörofizyolojik izleme, somatosensoryel uyarılmış potansiyel, motor uyarılmış potansiyel

Sum mary

Öz

Introduction

Intraoperative neuromonitoring (IN), which contains measurements of blood pressure, electrocardiogram, and other monitoring, is an effort to practice “primum non nocere,” one of the principal rules of medicine written in the Hippocratic Oath, with the help of the latest computing and electronic technology. Monitoring of vital signs during surgery has been performed for many years. Developments in computing and

electronic technology have led to progress in monitoring basic neurophysiologic systems and saving data intraoperatively and thus creating the modern technique of IN. The aims of IN are to predict dangers by monitoring tissues and systems at risk moment-by-moment and to decrease the effects of malicious insults when they are still reversible. IN should be considered as a medical-technological effort that can improve personal and social joy and decrease economic losses by avoiding or decreasing postoperative morbidity, which is also in line with professional principles. IN

Turk J Neurol 2016;22:51-54 Kubilay Varlı; Intraoperative Neuromonitoring

was first performed in operating rooms of some universities in the 1970s and quickly became routine practice. Early IN practices were electrophysiologic investigations performed in operating rooms and these had a long history. Wilder Penfield, a neurosurgeon, who had a good electrophysiology education is known as the founder of IN. He performed studies with Boldrey about somatic motor and sensory representation using electrical stimulation in 1937 and with Rasmussen on mapping epileptogenic areas using electrical stimulation of the cortex (1,2). He defined areas of cortical function and sensory and motor homunculus in these well-known studies. Another neurosurgeon, Ojeman (3), followed Penfield. He mapped the temporal lobe in patients on which he operated using electrical stimulation of the cortex and defined areas of memory and speech in awake patients during operations. In later years, the auditory cortex, dorsal column nuclei, cochlear nucleus, and inferior colliculus were defined by electrical stimulation (4,5). All these studies were precursors of IN and with the help of improvements in computing and electronic technology, IN became routine practice in operating rooms in the 1970s. In the late 1960s, monitoring of the facial nerve was routine practice (6) and it was followed by monitoring of the trigeminal nerve during microvascular decompression surgery for hemifacial spasm (7), monitoring of the auditory potentials (8), and monitoring of multiple cranial nerves at the same time during skull base operations in the late 1980s (9). With the development of magnetic and electrical stimulation of the cortex, cortical and spinal motor systems could be monitored intraoperatively (10,11). IN techniques then began to be used all over the world and performed in all operations of the central nervous system. Many neurosurgeons became pioneers of IN techniques in Turkey (12).

Intraoperative Neuromonitoring Techniques

All modalities used in clinical electrophysiology laboratories can also be used for IN. The types of IN techniques that would be used in an operation depends on the type of operation and the part of nervous system that is under risk. In addition to methods used in electrophysiology laboratories, awake anesthesia and uncovered nervous system provide fascinating investigations and monitoring including corticography, mapping, and detection of speech areas can be performed that cannot usually be performed in daily practice. Table 1 shows electrophysiologic monitoring and research methods that can be used intraoperatively.

One of the most commonly used IN techniques is “somatosensorial-evoked potentials” (SEP). SEP is commonly used in carotid endarterectomy because of its high sensitivity to cerebral blood flow (13); it is also used in scoliosis surgery (14). However, use of SEP alone has two disadvantages. First, averaging of many stimuli to get a clear SEP response takes a long time and instantaneous events can be missed or artefacts caused by cautery prevent obtaining a clear SEP response and cause more delay. Second, monitoring with SEP alone has a high percentage of false negative results - SEP responses are normal but the operation results in neurologic deficit (15). The percentage of false negativity dramatically decreased after transcortical electrical stimulation was used in operating rooms. Also, getting a response with one stimulation causes instantaneous monitoring and also makes performing mapping technique easier. Using

compound techniques for IN (Figure 1) including SEP, motor-evoked potentials (MEPs), and spinal motor potentials (D and I waves) have also reduced the percentage of false negativity nearly to zero, and decreased the risk of postoperative neurologic deficit and results with 92% specificity and 99% sensitivity (16).

IN contributes to detecting surgical borders sensitively with many aspects. The use of IN techniques including mappings of cortex, spinal cord and brainstem, electrocorticography, phase change studies in cerebellopontine angle tumors, cauda equina and tethered cord operations decreases morbidity and protects patient’s functional health by helping to detect nerves (Figure 2, 3). Visual evoked potentials and brainstem auditory evoked potentials (BAEP) especially in “cerebellopontine angle tumors” operations are used but less mentioned. We use BAEP in “cerebellopontine angle tumors” operations in our clinical practice.

Intraoperative Neuromonitoring Cost and Efficiency

Efficiency of IN is well studied. IN is, no doubt, efficient in monitoring of cerebral blood flow, detecting the margins of tumor resection and cortical ablation, fixating cranial nerves in operations of cerebellopontine angle and brainstem, securing hearing, functional mapping, fixating nerves and filum terminale in operations of

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Table 1. Intraoperative neuromonitoring techniquesSomatosensory Evoked PotentialsSomatosensory cortical evoked potentials by peripheral nerve stimulationSpinal cord evoked potentials by peripheral nerve stimulationSpinal cord evoked potentials by spinal cord stimulationPhase change studies

Motor Evoked PotentialsSpinal evoked potentials by motor cortex stimulation (spinal MEP/D-I waves)Muscle evoked potentials by motor cortex stimulation (brain-muscle MEP)Muscle and/or sensory potentials by peripheral nerve stimulation Motor cortex/brainstem/spinal cord mappings

Spinal Cord StimulationMuscle evoked potentials (spinal-muscle MEP) (myogenic MEP) Peripheral nerve evoked potentials (neurogenic MEP)

Visual Evoked PotentialsBrainstem Auditory Evoked PotentialsFree-run EMGReflex StudiesF waveH reflexPudental reflex

ElectroencephalographyScalp EEGElectrocorticographyMEP: Motor-evoked potential, EEG: Electroencephalogram, EMG: Electromyogram

Turk J Neurol 2016;22:51-54Kubilay Varlı; Intraoperative Neuromonitoring

tethered cord and cauda equina (9). But some believe that efficiency and essentiality of IN are overestimated. They argue that IN increases the expenses of operations, its importance is overestimated and decrease in percentage of complications is due to improvements in surgical technology. These arguments are partly true.

IN definitely imposes additional cast upon operations. But its cost can easily be measured. On the other hand, calculating the cost of a neurological complication is very hard. Toleikis (17) showed that the cost of a complication in pedicle screw surgery is equal to the cost of 50 patients’ IN for the same surgery. Personal expanses, effects on quality of life, effects on family members are not counted in calculation of the cost of IN in patients who had a complication because physical and psychological costs can’t be counted. IN can increase the cost in one patient but it doesn’t increase public health costs (18).

Intraoperative Neuromonitoring in Turkey and the World

Practice of IN in Turkey is problematic. IN is used in orthopedic and neurosurgical operations but in small numbers considering the development of medical practice in Turkey. In

many developed countries, IN became a “sine qua non” practice in orthopedic and neurosurgical operations and the number of studies about IN exceeded thousands (19). But practice of IN and studies about IN are in very small numbers in Turkey.

Social Security Institution, the buyer and payer of health services in Turkey determine in which operations a payment is made when IN is used (20). But this must not mean only in these operations, IN can bu used. Surgeons can use IN in every kind of operation when they need. The amounts of payment for INs are determined in “guide for budget implementations”. These amounts were changed many times because they were not determined realistically. On the other hand, amounts of payment that will be made to doctors are very small and because of this, neurologists who are only allowed to use IN by laws (21,22,23), are not interested in IN. Therefore, IN is used by someone who doesn’t have an education about it. IN performed by someone who doesn’t have an education about electrophysiology, doesn’t have a scientific value and won’t give reliable information. Because of this, practice of IN is limited by administrators. As shown in Table 1, all IN modalities performed in operations are modalities that are performed in clinical neurophysiology laboratories. Only neurologists are authorized to perform IN (21). Letting anyone to perform these procedures which are more complicated than ones performed in clinical neurophysiology laboratories and may require immediate decision, must be unacceptable for surgeons. Not to make an IN is better than making a bad IN. There are also problems about peforming IN and education of IN performers abroad but at least some rules are edited for IN performers ın United States and Canada. Unfortunately, suggestions of Turkish Clinical Neurophysiology Electroencephalogram-Electromyogram Society about education, authority, pricing and legal infrastructure for IN, hasn’t been accepted until now. All sides must come together and discuss to find solutions and make decisions before problems get bigger.

Ethics

Peer-rewieved: Internal peer-reviewed.

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Figure 1. A multimodal monitoring during a temporal mass excision (bilateral tibial somatosensorial-evoked potential, median somatosensorial-evoked potential, motor-evoked potential by transcortical electrical stimulation, free-run electromyogram)

Figure 2. Cortical stimulation, electrocorticography and phase change studies can be performed with the use of sequential cortical electrodes (in this image, cortical area is being investigated by cortical stimulation induced speech cessation)

Figure 3. Investigation of whether facial or trigeminal nerve is stimulated with the use of direct nerve stimulation during a cerebellopontine angle tumor operation

Turk J Neurol 2016;22:51-54 Kubilay Varlı; Intraoperative Neuromonitoring

References1. Penfield W, Boldrey E. Somatic motor and sensory representation in cerebral

cortex of man as studied by electrical stimulation. Brain 1937;60:389-443.2. Penfield W, Rasmussen T. The cerebral cortex of man: A clinical study of

localisation of function. 1950, Macmillan: NY.3. Ojeman GA. Brain organization for language from the perspective of

electrical stimulation mapping. Behavioral and Brain Sciences/Volume 6/Issue 02/June 1983, pp 189-206.

4. Celesia GG, Broughton RJ, Rasmussen T, Branch C. Auditory evoked responses from the exposed human cortex. Electroencephalogr Clin Neurophysiol 1968;24:458-466.

5. Møller AR, Janetta PJ. Evoked potentials from the inferior colliculus in man. Electroencephalogr Clin Neurophysiol 1982;53:612-620.

6. Hilger J. Facial nerve stimulator. Trans Am Acad Ophtalmol Otolaryngol. 1964,68;74-76.

7. Grundy B. İntraoperative monitoring of sensory evoked potentials. Anesthesiology 1983;58:72-87.

8. Freidman WA, Kaplan BJ, Gravenstein D, Rhoton AL. İntraoperative brain-stem auditory evoked potentials during posterior fossa microvascular decompression. J Neurosurg 1985;62:552-557.

9. Moller AR. Electrophysiological monitoring of cranial nerves in operation in the skull base, in Tumors of the Cranial Base: Diagnosis and Treatment. Sekhar LN, Schramm Jr VL. Editors. Futura Publishing Co: Mt. Kisco, NY, 123-132.

10. Barker AT, Jalinous R, Freeston IL. Non-invasive magnetic stimulation of the human motor cortex. Lancet 1985;1:1106-1107.

11. Marsden CD, Merton PA, Merton HB. Direct electrical stimulation of cortikospinal motor pathways through the intact scalp in human subjects. Adv Neurol 1983;39:387-391.

12. Zileli M. Nöroşirurjide elektrofizyolojik monitörleme teknikleri. Klinik nörofizyoloji EEG-EMG Derneği Yayınları, No: 3,1994.

13. Haupt WF, Horsh S. Evoked potential monitoring in carotid surgery: A review of 994 cases. Neurology 1992;42:835-838.

14. Diab M, Smith AR, Kuklo TR. Neural complications in the surgical treatment of adolescent idiopathic scoliosis. Spine 2007;32:2739-2763.

15. Nuwer MR, Dawson EG, Carlson LG, Kanim LEA, Sherman JE. Somatosensory evoked potential spinal cord monitoring reduces neurologic deficits after Scoliosis surgery: Results of a large multicenter survey. Electroencephalography and Clinical Neurophysiology 1995;96:6-11.

16. Sutter M, Deletis V, Dvorak J, Eggspuehler A, Grob D, MacDonald D, Mueller A, Sala F, Tamaki T. Current opinions and recommendations on multimodal intraoperative monitoring during spine surgeries. Eur Spine J 2007;16(Suppl 2):232-237.

17. Toleikis JR. Neurophysiological monitoring during pedicle screw placemen, in neurophysiology in neurosurgery, Editors Deletis V, Shils JL, Amsterdam, Elsevier, 2002, 231-264.

18. Wilson L, Lin E, Lalwani A. Cost-effectiveness ofintraoperative facial nerve monitoring of facial nerve monitoring in middle ear or mastoid surgery. Laryngoscope 2003;113:1736-1745.

19. Nuwer MR, Cohen BH, Shepard KM. Practice patterns for intraoperative neurophysiologic monitoring. American Academy of Neurology, Contemporary Issues 2013. 1156-1158.

20. T. C. SGK Başkanlığı, Genel Sağlık Sigortası Genel Müdürlüğü, 703.365 Kodlu Intra-operatif Nöromonitorizasyon işlemi ile ilgili duyuru. 07.11.2012.

21. Tababet ve şuabatı sanatlarının tarzı icrasına dair kanun. Madde 1 ve 3 Kanun No:1219, Resmi Gazete: 14.04.1928-863.

22. Sağlık Bakanlığı ve bağlı kurulıuşlarının teşkilat ve görevleri hakkında kanun hükmünde kararname ile bazı kanunlarda değişiklik yapılmasına dair kanun. Madde 46 Ek madde: 11. Kanun No: 6514, 18.01.2014, Resmi gazete: Sayı: 288886.

23. Tıp ve Diş Hekimliğinde Uzmanlık Eğitimi Yönetmeliği, EK-3 Nolu Çizelge, Resmi Gazete 18.07.2009/27292, Tıpta Uzmanlık Yan Dalları, Bağlı Ana Dalları ve Eğitim Sürelerine Dair Çizelge.

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Objective: Patients with pain or numbness without motor deficits are the most common group referred to electrophysiology laboratories as suspected radiculopathy. We wanted to investigate whether electromyography (EMG) was useful for this group in the diagnosis or therapy of radiculopathy. Our aim was to investigate the correlation and classification of EMG and magnetic resonance imaging (MRI) findings in the diagnosis of suspected radiculopathy.

Materials and Methods: We included 74 patients with a ≥2-month history of numbness and pain in the neck and back that radiated into the arm or leg. Patients with diabetes mellitus, previous disc or spine operation, polyneuropathy, spinal cord diseases (tumor, infection or syrinxs), motor deficits, and abnormal nerve conduction studies were excluded.

Results: The mean age of the patients was 51.58±11.53 years. In total, 41 (55.4%) patients were women and 33 (44.6%) were men; 48.8% (n=36) showed cervical radiculopathy and 51.2% (n=38) exhibited lumbosacral radiculopathy. The most common MRI finding was protrusion (37.8%), and the most common EMG finding was re-innervation (59.5%). The correlation of MRI and EMG findings was significant in lumbar radiculopathy (p=0.007), but not in the cervical radiculopathy results (p=0.976).

Conclusion: EMG and MRI findings were compatible for lumbar radiculopathy, but not for cervical radiculopathy in mild to moderate grades.

Keywords: Suspected radiculopathy, electromyography, magnetic resonance imaging

Amaç: Elektrofizyoloji laboratuvarına şüpheli radikülopati tanısıyla gönderilen hastaların çoğu motor defisit olmadan ağrı ve uyuşukluk şikayetiyle başvuran gruptur. Biz elektromiyografinin (EMG) bu grup hastalarda radikülopatinin tanı ve tedavisinde faydalı olup olmadığını araştırmak istedik. Amacımız şüpheli radikülopati tanısında EMG ve manyetik rezonans görüntüleme (MRG) bulgularının sınıflandırılması ve korelasyonunun araştırılmasıdır.

Gereç ve Yöntem: Çalışmaya en az 2 aydır boyunda ve belde başlayıp kola veya bacağa yayılan ağrı ve uyuşması olan 74 hasta dahil edildi. Diabetes mellitus, geçirilmiş disk veya omurga operasyonu, polinöropati, spinal kord hastalığı olanlar (tümör, enfeksiyon veya sirinks gibi) ile motor defisit ve anormal sinir iletim çalışmaları olan hastalar dışlandı.

Bulgular: Hastaların yaş ortalaması 51,58±11,53 idi. Çalışmaya dahil edilen 41 (%55,4) hasta kadın, 33 (%44,6) hasta erkekti. Hastaların %48,8’inde (n=36) servikal radikülopati %51,2’sinde (n=38) lumbosakral radikülopati saptandı. En sık görülen MRG bulgusu protrüzyon (%37,8), en sık görülen EMG bulgusu re-innervasyondu (%59,5). EMG ve MRG bulgularının korelasyonu lomber radikülopatide istatistiksel olarak anlamlıydı (p=0,007), ancak servikal radikülopati olanlarda anlamlı değildi (p=0,976).

Sonuç: Hafif ve orta evre radikülopatide MRG ve EMG sonuçları lomber radikülopati de uyumlu saptandı, ancak servikal radikülopatide uyumlu değildi.

Anahtar Kelimeler: Şüpheli radikülopati, elektromiyografi, manyetik rezonans görüntüleme

Sum mary

Öz

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Original Article / Özgün AraştırmaDO I:10.4274/tnd.99896Turk J Neurol 2016;22:55-59

Ad dress for Cor res pon den ce/Ya z›fl ma Ad re si: Yıldız Arslan MD, Tepecik Training and Research Hospital, Clinic of Neurology, İzmir, Turkey Phone: +90 232 344 30 52 E-mail: [email protected]


Correlation of Electromyography and Magnetic Resonance Imaging Findings in the Diagnosis of Suspected Radiculopathy

Şüpheli Radikülopati Tanısında Elektromiyografi ve Manyetik Rezonans Görüntüleme Bulgularının Korelasyonu

Yıldız Arslan1, Ebru Yaşar2, Yaşar Zorlu1

1Tepecik Training and Research Hospital, Clinic of Neurology, İzmir, Turkey2Şevket Yılmaz Training and Research Hospital, Clinic of Neurology, Bursa, Turkey

Turk J Neurol 2016;22:55-59 Arslan et al.; EMG and MRI Finding of Suspected Radiculopathy

Introduction

Cervical and lumbosacral radiculopathy is a common disorder that typically affects people in the fourth and fifth decades of life (1). Radiculopathy is characterized by inflammation or compression of nerve roots, producing pain and tingling, numbness, or even motor deficit along the distribution of the effected nerve root (2,3). This process typically involves a herniated nucleus pulposis that compresses the nerve root within the spinal canal; alternatively, there may be an intrinsic lesion within the structure of the nerve root, such as a tumor, or demyelinating disease might underlie. If the root is only irritated, and not compressed, radiculitis results (2,4). The other common cause of radiculopathy is spinal stenosis, which results from a combination of degenerative spondylosis, ligament hypertrophy, and spondylolisthesis (4). Symptoms of pain, numbness, and/or tingling may be mild or moderate, but radiculopathy is associated with motor weakness in severe cases. Efficient diagnosis and treatment can minimize pain, disability, and the direct and indirect costs of care (1). In most patients, symptoms are of short duration and resolve without treatment. Neurophysiologic tests in combination with neuroimaging, especially magnetic resonance imaging (MRI) because of its high-resolution, have traditionally been used to assess patients with radiculopathy (5,6,7). Electromyography (EMG) demonstrates a measure of the physiologic integrity of nerve roots, while MRI shows structural details of the roots and their surrounding tissues. Studies that examined the specific utility of EMG and MRI in the evaluation of clinical radiculopathy showed that although both are useful diagnostic tools, they have some limitations. EMG is likely to be negative if performed too early and may remain negative in radiculopathies that are mild or predominantly sensory, whereas MRI may reveal structural spinal abnormalities that are not clinically relevant, such as herniated intervertebral discs and spinal stenosis, which are frequently found in asymptomatic individuals or are irrelevant to the patients’ symptoms (7,8).

In the present study, we investigated the correlation between EMG and MRI findings in patients with suspected radiculopathy.

Materials and Methods

PatientsThe medical records of 360 patients who were referred to our

neurophysiology laboratory from neurology and neurosurgery outpatient clinics with a clinical pre-diagnosis of radiculopathy without motor deficit, between the dates June 2011 and May 2013, were retrospectively reviewed. A total of 74 patients (55.4% women) were included with a mean age of 51.58±11.53 years. The inclusion criteria were presence of ≥2-month history of numbness and pain in the neck and back that radiated to the arm or leg; being assessed with both neuroimaging and neurophysiologic studies; and having normal nerve conduction results and no motor deficits. A minimum of 8-week duration of symptoms was identified among the inclusion criteria to be able to observe denervation potentials and re-innervation. Patients with diabetes mellitus; history of intervertebral disk or spinal operations; polyneuropathy; spinal cord diseases such as tumors, infection or syrinx; abnormal nerve conduction; and motor deficit were excluded from study such that only mild and moderate radiculopathies were investigated.

In this retrospective study the data of subjects were collected with the permission of each subject and the study was performed in conformity with the Code of Ethics of the World Medical Association (Declaration of Helsinki), printed in the British Medical Journal (18 July 1964).

MRI findings were classified into four categories: degenerative abnormalities, bulging disc, protrusion, and nerve root compression. Similarly, EMG findings were divided into four groups: denervation, re-innervation, chronic neurogenic changes, and normal. Radiculopathy was graded as mild, moderate or severe. MRI and EMG findings and their correlation were classified and analyzed according to the following classification:

Mild: No motor or sensorial deficits, normal or re-innervation findings in EMG and normal nerve conduction study (NCS) findings. Degenerative abnormalities and/or bulging disc in MRI.

Moderate: No motor deficit, the presence of dermatomal hypoesthesia or hyperalgesia, normal NCS findings. Re-innervation, chronic neurogenic changes and/or denervation findings in EMG. Protrusion and nerve root compression findings in MRI.

Severe: The presence of motor and sensorial deficits. Denervation and chronic neurogenic changes findings in EMG. Nerve root compression in MRI.

Electromyography DataWe performed routine nerve conduction studies in all patients

suspected to have radiculopathy using the Medelec Synergy EMG/EP system (Oxford Instruments Medical, Inc., Oxford, UK). Nerve conduction studies and EMG were performed according to the 1999 guidelines of the American Association of Electrodiagnostic Medicine (AANEM). Ulnar, median motor and sensory nerves and sural, posterior tibial, and peroneal nerves were studied; median and tibial F-responses were also recorded. Concomitant polyneuropathy and nerve entrapment were investigated and excluded. A standard EMG examination using concentric needles was performed on each patient to assess for cervical and lumbosacral radiculopathy. The following muscles were examined for cervical radiculopathy: deltoid (C5/C6), biceps brachii (C5/C6), triceps brachii (C6/C7/C8), brachioradialis (C5/C6), extensor digitorum communis (C6/C7), and abductor pollicis brevis (C8/Th1). The following muscles were examined for lumbosacral radiculopathy: tibialis anterior (L4/L5), peroneus longus (L5/S1), gastrocnemius medialis (S1/S2), and rectus femoris (L2/L3/L4). The presence of abnormal spontaneous fibrillation and/or positive sharp waves were interpreted as indicative of denervation, and a reduced number of motor unit action potentials (MUAPs) of increased duration was taken as a sign of chronic neurogenic change. Polyphasic and/or neurogenic (increased amplitude and duration) MUAPs were taken to indicate re-innervation. At least two muscles innervated by the same root were studied and interpreted. EMG findings of these muscles were recorded according to the pathologic root level as demonstrated using MRI.

Magnetic Resonance Imaging DataMRI was performed using a standardized cervical and

lumbar spine protocol (sagittal and transverse T1- and T2-weighted sequences with a 4-mm slice thickness) with a Philips Ingenia 1.5-T unit (Philips, Amsterdam, The Netherlands). Two experienced radiologists who were blinded to the patients’ characteristics interpreted all MRI scans independently. The

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Turk J Neurol 2016;22:55-59Arslan et al.; EMG and MRI Finding of Suspected Radiculopathy

presence of degenerative abnormalities, bulging discs, protrusion, and nerve root compression were identified using the definitions of the American Society of Neuroradiology. Radiologic nerve root compression was the main outcome measure. Bulging disc was defined as the containment of the nucleus pulposus remains within the annulus fibrosus whereby the spinal canal was not narrowed, whereas protrusions occupied a wider space and narrowed the canal.

Statistical AnalysesStatistical analysis of the study data was performed using the

Statistical Package for Social Sciences (SPSS) software for Windows (version 20.0; IBM Corp., Armonk, NY, USA). Descriptive statistics were performed to compare MRI and EMG findings and cervical and lumbar radiculopathy separately. Pearson’s χ² (4x4) test was used to assess the statistical significance of these associations; p<0.05 was taken to indicate statistical significance.

Results

The patients’ mean age was 51.58±11.53 years. In total, 41 (55.4%) patients were women and 33 (44.6%) were men; 48.8% (n=36) had cervical radiculopathy and 51.2% (n=38) had lumbosacral radiculopathy. The most common MRI finding was protrusion (37.8%), and the most common EMG finding was reinnervation (59.5%). Four patients had normal MRI findings; of these, two exhibited reinnervation on EMG, and the other two showed chronic neurogenic changes on EMG. EMG findings were normal in 12 patients; 6 of which revealed protrusion on MRI, and 6 had bulging on MRI. Statistical analyses were performed in all

patients for the comparison of EMG and MRI findings, and also for the comparison of cervical and lumbar radiculopathies. The two groups showed significant differences with regard to the MRI and EMG findings (p=0.037). Lumbar radiculopathy findings were also significantly different between the two groups (p=0.007); but there was no significant difference in cervical radiculopathy findings (p=0.976). The overall MRI and EMG findings are described in Table 1. The cervical and lumbar findings are provided separately in Tables 2 and 3, respectively. MRI findings (normal, bulging, protrusion, and root compression) and EMG findings (normal, re-innervation, chronic neurogenic changes, and denervation) are also shown in the tables. Twelve patients exhibited chronic neurogenic changes, the most common of which was bulging on MRI (n=7). A total of 44 patients revealed re-innervation: 16 had protrusion, 15 had root compression, and 11 had bulging on MRI. Only six patients had denervation potentials: two had root compression, three had protrusion, and one had bulging.

The most commonly involved root levels were C6-7 (n=18), L4-5 (n=19), and L5-S1 (n=18) in MRI. The second most common level of involvement was C5-6 (n=13); involvement at L3-4, C4-5, and C7-8 levels was seen each in one patient. The remaining three lesions were at C8-T1. MRI and EMG findings are presented in Table 4 by root levels.

Discussion

The literature on the relative efficacy of MRI and EMG in the evaluation of radiculopathy and degree of correlation between these diagnostic tests is limited. A major restriction of diagnostic

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Table 1. Electromyography and magnetic resonance imaging findings of all patients (n=74)

Total MRI findings

EMG findings Degenerative abnormalities

Bulging Protrusion Root compression

Total

Normal 0 (0%) 6 (24%) 6 (21.4%) 0 (0%) 12 (16.21%)

Chronic neurogenic changes 2 (50%) 7 (28%) 3 (10.7%) 0 (0%) 12 (16.21%)

Reinnervation 2 (50%) 11 (44%) 16 (57.1%) 15 (88.2%) 44 (59.45%)

Denervation 0 (0%) 1 (4%) 3 (10.7%) 2 (11.8%) 6 (8.10%)

Total 4 (5.40%) 25 (33.78%) 28 (37.83%) 17 (22.97%) 74 (100%)EMG: Electromyography, MRI: Magnetic resonance imaging

Table 2. Electromyography and magnetic resonance imaging findings of patients with cervical radiculopathy (n=36)

Cervical MRI findings



Total

Normal 0 (0%) 1 (10%) 4 (17.4%) 0 (0%) 5 (13.88%)

Chronic neurogenic changes 0 (0%) 2 (20%) 3 (13%) 0 (0%) 5 (13.88%)

Reinnervation 1 (100%) 6 (60%) 13 (56.5%) 2 (100%) 22 (61.11%)

Denervation 0 (0%) 1 (10%) 3 (13%) 0 (0%) 4 (11.11%)


Turk J Neurol 2016;22:55-59 Arslan et al.; EMG and MRI Finding of Suspected Radiculopathy

studies of nerve root involvement is the absence of a gold standard method, because of the inherent limitations of all diagnostic methods and operative findings, which renders comparison of their relative diagnostic sensitivity controversial (3). Radiologic studies using MRI techniques only reveal structural abnormalities, which may also be present in asymptomatic patients or may be unrelated to clinical findings (8). MRI does not demonstrate inflammation of disk bulging or protrusion, and thus may not be able to distinguish between symptomatic and asymptomatic discs (9,10). However, symptom onset and root compression and/or irritation may not begin simultaneously. It is difficult to be certain that current symptoms provide chronic EMG changes, even if the symptom duration is chronic or an MRI abnormality, which frequently cannot be dated, is related to current symptoms (11). Therefore, neither root compression as indicated by MRI, nor clinical symptoms can be considered gold standard findings of radiculopathy.

EMG results remain negative if EMG is performed before denervation or after the disappearance of denervation findings, or if reinnervation has not occurred (12,13). Patients with ≥2 months duration of symptoms were chosen in this study to observe denervation potentials and reinnervation. Despite this

classic data, Dillingham et al. (14) suggested that cervical and lumbosacral radiculopathy showed no evidence of correlation between spontaneous activity in the paraspinal and in other major proximal, or distal muscles and symptom duration (15). However, we aimed to observe the denervation potentials and re-innervation findings in this study. Chronic neurogenic changes typically persist indefinitely after radiculopathy and it is common to find such abnormalities for years after patients first exhibit symptoms. In our study, reinnervation was seen in 59.5% of the patients. This relatively high rate may be due to normal polyphasic findings, which may occur in 10% to 20% of normal limb muscles (13). We also observed a good correlation between EMG and MRI findings in most (78.37%) patients who exhibited clinical signs of cervical or lumbosacral radiculopathy. The studies included in the AANEM review used a combination of clinical and radiologic findings; the nine studies cited in the final review were characterized by an overall needle EMG sensitivity of 50% to 71% in the context of diagnosis of radiculopathy, which the review described as moderate diagnostic sensitivity. Studies with a greater number of clinical motor deficits also reported higher sensitivities. According to Nardin et al., (7) compatibility between EMG and MRI findings was highest in patients with

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Table 4. Electromyography and magnetic resonance imaging findings according to root levels

MRI findings EMG findings

Root level

Degenerativeabnormalities


Normal Chronic neurogenic changes

Denervation Re-innervation Total

C4-5 0 0 1 0 0 0 0 1 1

C5-6 0 2 9 2 2 4 0 7 13

C6-7 1 7 10 0 3 2 2 11 18

C7-8 0 0 1 0 0 0 1 0 1

C8-T1 0 1 2 0 0 0 1 2 3

L3-4 0 1 0 0 0 1 0 0 1

L4-5 0 6 3 10 4 1 1 13 19

L5-S1 3 8 2 5 3 5 1 9 18

Total 4 25 28 17 12 13 6 43 74EMG: Electromyography, MRI: Magnetic resonance imaging

Table 3. Electromyography and magnetic resonance imaging findings of patients with lumbar radiculopathy (n=38)

Lumbar MRI findings



Total

Normal 0 (0%) 5 (33.3%) 2 (40%) 0 (0%) 7 (18.42%)

Chronic neurogenic changes 2 (66.7%) 5 (33.3%) 0 (0%) 0 (0%) 7 (18.42 %)

Re-innervation 1 (33.3%) 5 (33.3%) 3 (60%) 13 (86.7%) 22 (57.89%)

Denervation 0 (0%) 0 (0%) 0 (0%) 2 (13.3%) 2 (5.26%)


Turk J Neurol 2016;22:55-59Arslan et al.; EMG and MRI Finding of Suspected Radiculopathy

a clear radicular syndrome accompanied by abnormal clinical findings (motor, sensory, or reflexes) consistent with radiculopathy (12). We also observed good agreement between diagnostic test results in patients without motor deficits and F-waves in normal ranges. Based on these data, it is important to understand that a negative EMG or MRI study for radiculopathy does not rule out the presence of disease, and that clinical findings, particularly in motor deficits. In our study, a significant difference was found between cervical and lumbar radiculopathy. Additionally, EMG and MRI were compatible for lumbar radiculopathy (p<0.05), but not for cervical radiculopathy (p>0.05). This may have been due to differences in anatomy, myotomal innervation, spinal canal narrowness, or spinal nerve variance between the lumbar and cervical spines. Studies in the literature have reported that needle EMG was particularly helpful in determining false-positivity rates of lumbar spinal MRI, which are quite high, with 27% of normal subjects with disc protrusion in lumbar MRI; false-positivity rates for cervical MRI are much lower. However, we found much greater diagnostic discrepancy between MRI and EMG findings in cervical radiculopathy. Radiculopathies may also occur without any structural findings on MRI or without any EMG findings (4). An alternative possible explanation for this discrepancy might relate to an etiologic association between radiculopathy and inflammation, or permanent denervation activity with a resolved herniated disc (10).

This study had several limitations. First, we did not examine the paraspinal muscles. We attempted to reduce the effect of this shortcoming by including patients with ≥2-month symptom duration referable to the disappearance of fibrillation potentials. However, denervation potentials might persist for years, even in paraspinal muscles. A second limitation concerned the clinical examination findings used to categorize patients. We only reviewed the muscle strength before the EMG study because of the retrospective design of our study; however, it would have been worthwhile if we had also been able to look for dermatomal hypoesthesia to grade radiculopathy and distinguish between mild and moderate cases. Finally, we had very few cases of cervical root compression (n=2) compared with lumbar root compression (n=15), which might account for the reported statistical difference.

Conclusion

In conclusion, we would like to emphasize the discrepancy between cervical and lumbar radiculopathy findings and the importance of obtaining reliable data before treatment or surgery for patients with radiculopathy with typical clinical signs and no motor deficits. EMG and MRI evidently represent complementary diagnostic tools for lumbosacral radiculopathy; however, reliable data are lacking for cervical radiculopathy. In our opinion, with the exception of those with severe radiculopathy, all patients should be managed conservatively. If root compression is present on MRI, EMG might help to discern the need for surgery. The question as to whether patients without motor deficits (i.e., those with only pain and numbness) should undergo surgery if EMG shows positive results (denervation or re-innervation) requires further prospective randomized studies with larger samples remains to be answered.

Ethics

Ethics Committee Approval: This retrospective study was approved by the Kocaeli Education and Research Hospital Local Ethics Committee.

Informed Consent: A consent form was completed by all participants.Peer-review: Internal peer-reviewed.


Concept and Design: Yıldız Arslan, Data Collection or Processing: Yıldız Arslan, Ebru Yaşar, Analysis or Interpretation: Yıldız Arslan, Ebru Yaşar, Literature Search: Yıldız Arslan, Writing: Yıldız Arslan, Editing: Yaşar Zorlu, Medical Practices: Yıldız Arslan, Ebru Yaşar.



References1. Hakimi K, Spanier D. Electrodiagnosis of cervical radiculopathy. Physical

Medicine and Rehabilitation Clinics of North America 2013;24:1-12.2. Nasca RJ. Cervical radiculopathy: Current diagnostic and treatment options.

J Surg Orthop Adv 2009;18:13-18.3. Soltani ZR, Sajadi S, Tavana B. A comparison of magnetic resonance imaging

with electrodiagnostic findings in the evaluation of clinical radiculopathy: A cross-sectional study. Eur Spine J 2014;23:916-921.

4. Dillingham T. Electrodiagnostic approach to patients with suspected radiculopathy. Phys Med Rehabil Clin N Am 2002;13:567-588.

5. Ashkan K, Johnston P, Moore AJ. A comparison of magnetic resonance imaging and neurophysiological studies in the assessment of cervical radiculopathy. British Journal of Neurosurgery 2002;16:146-148.

6. So YT, Weber CF, Campbell WW. American association of electrodiagnostic medicine, American academy of physical medicine and rehabilitation practice parameter for needle electromyographic evaluation of patients with suspected cervical radiculopathy: Summary statement. Muscle Nerve 1999;22:209-211.

7. Nardin R, Patel M, Gudas T, Rutkove S, Raynor E. Electromyography and magnetic resonance imaging in the evaluation of radiculopathy. Muscle Nerve 1999;22:151-S155.

8. Lee JH, Lee SH. Physical examination, magnetic resonance imaging, and electrodiagnostic study of patients with lumbosacral disc herniation or spinal stenosis. J Rehabil Med 2012;44:845-850.

9. Robinson LR. Electromyography, magnetic resonance imaging, and radiculopathy: It’s time to focus on specificity. Muscle Nerve 1999;22:149-150.

10. Coster S, de Brujin S, Tavy J. Diagnostic value of history, physical examination and needle electromyography in diagnosing lumbosacral radiculopathy. J Neurol 2010;257:332-337.

11. Levin KH. Electromyography and magnetic resonance imaging in the evaluation of radiculopathy. Muscle Nerve 1999;8:1158-1159.

12. Inal EE, Eser F, Aktekin LA, Öksüz E, Bodur H. Comparison of clinical and electrophysiological findings in patients with suspected radiculopathies. Journal of Back and Musculoskeletal Rehabilitation 2013;26:169-173.

13. Tsao B. The electrodiagnosis of cervical and lumbosacral radiculopathy. Neurol Clin 2007;25:473-494.

14. Dillingham TR, Pezzin LE, Lauder TD, Andary M, Kumar S, Stephens RT. Steven S. Symptom duration and spontaneous activity in lumbosacral radiculopathy. Am J Phys Med Rehabil 2000;79:124-132.

15. Pezzin LE, Dillingham TR, Lauder TD, Andary M, Kumar S, Stephens RR, Shannon S. Cervical radiculopathies: Relationship between symptom duration and spontaneous EMG activity. Muscle Nerve 1999;22:1412-1418.

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Ad dress for Cor res pon den ce/Ya z›fl ma Ad re si: Zeynep Aydın Özemir MD, İstanbul University İstanbul Faculty of Medicine, Department of Neurology, Division of Clinical Neurophysiology, İstanbul, Turkey

Phone: +90 505 803 21 26 E-mail: [email protected] cei ved/Ge lifl Ta ri hi: 10.11.2015 Ac cep ted/Ka bul Ta ri hi: 11.02.2016

Objective: Absence status epilepticus (ASE) has been well recognized for many years, but its pathophysiology has not yet been illuminated and there are speculations about GABAergic mechanisms. We aimed to study the etiopathogenesis of ASE by using magnetic resonance-spectroscopy (MRS), which gives in vivo information about neuronal loss and/or dysfunction by correlating the results with age- and sex-matched normal healthy controls (HC).

Materials and Methods: Four patients with genetic generalized epilepsy (GGE), which was diagnosed in accordance with the International League Against Epilepsy criteria, with recurrent ASE were investigated. The control groups consisted of ten age- and sex-matched patients with HC and ten patients with GGE. MRS measurements of N-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine (Cr) were performed in the frontal lobes and thalamus bilaterally with a voxel size of 20x20x20 mm, the values of the patients were compared with those of the controls using appropriate statistical tests.

Results: In patients with ASE, NAA/Cr levels were decreased when compared with those with HC and GGE in the frontal lobes and thalamus. Moreover, frontal lobe Cho values and Cho/Cr ratios were elevated in all patients with GGE, and more pronounced in patients with ASE comparison with those with HC. There was a positive correlation of ASE with the frontal Cho/Cr ratio and a negative correlation with NAA/Cr ratios in patients with GGE (p=0.002, z=-0.745). The presence of absence seizures related negatively to the thalamic NAA/Cr ratio and NAA levels. Prognosis showed a negative correlation with thalamic NAA levels (p=0.026, z=-0.591) and the NAA/Cr ratio (p=0.013, z=-0.645).

Conclusion: Although our sample size was small due to the rarity of the condition, this first MRS study in patients with ASE showed that neuronal dysfunction in frontal lobes and thalamus was more pronounced when compared with those with GGE and related to poor prognosis. Our study suggested that the dysfunction in thalamocortical circuits might underlie ASE attacks.

Keywords: Absance, status epilepticus, magnetic resonance spectroscopy

Amaç: Absans status epileptikus (ASE) çok uzun yıllardır tanınan bir tablo olmakla birlikte patofizyolojisi henüz bilinmemektedir ve GABAerjik mekanizmalar üzerinde durulmaktadır. Bu çalışmada nöronal kayıp ve/veya disfonksiyon hakkında in vivo olarak bilgi veren manyetik rezonans spektroskopi (MRS) yapılarak ve sağlıklı kontrollerle (SK) kıyaslanarak ASE’nin etiyopatogenezini aydınlatmaya yönelik bilgiler edinmek amaçlanmıştır.

Gereç ve Yöntem: Tekrarlayan ASE atakları olan ve ‘Uluslararası Epilepsi ile Savaş Ligi’ tarafından yapılmış sınıflamaya göre genetik jeneralize epilepsi (GJE) tanısı almış dört hasta incelenmiştir. Talamus ve frontal loblara ayrı ayrı 20x20x20 mm boyutlarında vokseller yerleştirilmiş ve elde edilen N-asetil aspartat (NAA), kolin (Ko) ve kreatin (Kr) değerleri yaş ve cins olarak eşlenmiş on SK ve on diğer GJE tanısı almış olan kontrol gruplarıyla uygun istatistiksel yöntemlerle kıyaslanmıştır.

Investigation of Magnetic Resonance Spectroscopy Findings in Patients with Absence Status Epilepticus

Absans Status Epileptikusu Olan Hastalarda Manyetik Rezonans Spektroskopi Bulgularının Araştırılması

Zeynep Aydın Özemir1, Betül Baykan1, Ebru Nur Vanlı Yavuz1, Serra Sencer2

1İstanbul University İstanbul Faculty of Medicine, Department of Neurology, Division of Clinical Neurophysiology, İstanbul, Turkey2İstanbul University İstanbul Faculty of Medicine, Department of Radiology, İstanbul, Turkey

Sum mary

Öz

Turk J Neurol 2016;22:60-66Aydın Özemir et. al.; Absence Status Epilepticus and Magnetic Resonance Spectroscopy Findings

Introduction

Absence status epilepticus (ASE), which is classified under the “generalized” sub-group of “non-convulsive status epilepticus without coma” according to the latest classification (1), is an epileptic condition affects consciousness in varying degrees and may be accompanied by automatisms or mild myoclonic, tonic, atonic or autonomic phenomena (2). Alterations in behavior and consciousness of more than 5 minutes and presence of generalized epileptiform electroencephalographic (EEG) abnormalities during this period are required for the diagnosis of ASE. Although more frequent (about 20%) in patients with juvenile absence epilepsy (JAE), ASE may develop in genetic generalized epilepsy (GGE) at a rate of 5-10% (3,4). The mechanisms of absence seizures and ASE are not yet clear, but it is thought that the thalamocortical network is affected and that disorders in gamma-aminobutyric acid-mediated inhibitory mechanisms, which are normally effective in terminating seizures, and changes in N-methyl-D-aspartate receptors play a role in the pathogenesis. Also, it is not known whether ASE causes damage to the brain (5,6,7,8,9). Magnetic resonance spectroscopy (MRS) is a non-invasive, in vivo examination method for measuring rates of specific chemical metabolites in tissues (10). MRS makes measurements on three major metabolites, namely N-acetyl aspartate (NAA), creatine+phosphocreatine (Cr), and choline-containing compounds (Co) (Figure 1). When a decrease in NAA signal is observed, which is known to be present in neurons and their extensions (10,11), it is thought to be due to neuronal or axonal loss or metabolic disorder caused by mitochondrial dysfunction and these changes are generally considered to be irreversible (11,12,13). Although MRS studies have been conducted more on patients with focal epilepsy, especially patients with temporal lobe epilepsy, recent studies on patients with GGE are also available. Despite these studies had varying results, decreased NAA and NAA/Cr levels were detected in the frontal lobes (14,15) and the thalamus (16,17) of patients with GGE compared with controls. There are no previous MRS studies on patients with ASE. The aim of this study was to investigate the neurochemical changes in the frontal lobe and thalamus of patients with ASE using MRS and thus to illuminate the underlying etiopathogenesis, and to detect whether recurrent ASE attacks cause brain damage.


Selection and Grouping of Patients

Among the patients being followed up by the Neurology Department of İstanbul Faculty of Medicine, İstanbul University, patients who were diagnosed as having GGE in accordance with the International League Against Epilepsy (ILAE) classification (18) with consistent seizure semiology and history, EEG findings and other records were investigated. Among these, four patients with recurrent ASE attacks formed the study group. Ten patients with GGE and 10 previously healthy individuals with similar age and sex distributions were included in the study as the GGE group and healthy control (HC) group, respectively. Demographic and clinical data, interviews with patients and their relatives, and follow-up and treatment data were examined in detail from patients’ files. This study protocol was approved by İstanbul Medical Faculty Ethics Committee and patients were included in the study after obtaining written informed consents. The patient

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Bulgular: ASE hastalarında frontal lob ve talamus NAA/Kr oranları SK’lara ve diğer GJE’lilere göre düşük, ayrıca frontal lob Ko değerleri, Ko/Kr oranları ASE grubunda daha belirgin olmak üzere tüm GJE hastalarda normallere kıyasla yüksek saptanmıştır. GJE’li hastalarda ASE varlığı ile; frontal Ko/Kr oranı arasında pozitif, frontal NAA/Kr oranı arasında negatif, talamus NAA/Kr oranı arasında negatif (p=0,002, z=-0,745) ilişki kaydedilmiştir. Absans nöbet varlığı ile; talamus NAA/Kr oranı ve NAA düzeyi ile arasında negatif ilişki bulunmuştur. Prognoz ile talamus NAA düzeyi arasında (p=0,026, z=-0,591) ve NAA/Kr oranı arasında (p=0,013, z=-0,645) negatif korelasyon saptanmıştır.

Sonuç: Çok nadir rastlanması nedeniyle olgu sayımız az olmakla birlikte, ASE’li olgularda yapılan bu ilk çalışmada frontal loblarda ve talamusta MRS ile saptanan nöronal fonksiyon bozukluğunun ASE atakları olmayan GJE’lilere göre daha fazla olduğu ve bozukluğun prognozu olumsuz etkilediği gösterilmiştir. Çalışmamız talamo-kortikal devrelerdeki bu bozukluğun ASE ataklarının altında yattığını düşündürmüştür.

Anahtar Kelimeler: Absans, status epileptikus, manyetik rezonans spektroskopi

Figure 1. Voxels and obtained curves in patients for magnetic resonance spectroscopy examination. Voxels placed to include cortico-subcortical areas and obtained magnetic resonance spectroscopy values in a male patient aged 32 years with juvenile absence epilepsy; a, b) Frontal lobe voxels; c, d) Thalamic voxels

Turk J Neurol 2016;22:60-66 Aydın Özemir et. al.; Absence Status Epilepticus and Magnetic Resonance Spectroscopy Findings

group was evaluated in terms of syndrome diagnosis based on the ILAE syndrome classification (18), age of onset, duration of epilepsy, types of seizures, presence of absence, myoclonus, generalized tonic-clonic seizures and age of onset, frequency of these seizure types before and after treatment, date of most recent seizure, seizure trigger factors, past and current treatments, presence of discontinuation of medications duration treatment and if so, presence of recurrence, length of time without medication, duration of treatment, response to treatment, presence of psychiatric and other systemic diseases, and presence of remission and family history of epilepsy sub-groups were formed.

Magnetic Resonance Imaging and Proton Magnetic Resonance Spectroscopy

MRI and 1-H MRS examinations were performed in all patients and healthy volunteers in the Neuroradiology Department of İstanbul Faculty of Medicine, İstanbul University. MRI examinations were performed using an MRI unit (Magnetom Symphony, Siemens, Erlangen, Germany) with a 1.5 Tesla (T) superconducting magnet. Following acquisition of scout images in axial, sagittal, and coronal planes using standard head coil, axial, coronal and sagittal T2-weighted (A) turbo spin echo (TR/TE=5750/100 ms, NEX=1, slice thickness of 5 mm, matrix=512x512, FOV=220 mm), and coronal inversion recovery T1 (IR T1) (TR/TE=1960/4 ms, IT=1100 ms, NEX=1, slice thickness of 1.25 mm, matrix=512x512, FOV=220 mm) sequences were obtained. Following these sequences, 20x20x20 mm single voxels were placed separately to thalamic and frontal regions of both hemispheres using the stimulated-echo acquisition mode (TR/TE=1500/30 ms) and chemical shift selective excitation for water suppression (Figure 1). NAA, Co, and Cr peaks obtained from these voxels were compared proportionally. These single voxel values were processed using Syngo MRS software. Curves obtained after "curve fitting" and "curve correction" processes that were performed automatically by the software were checked by a neuroradiology practitioner. Erroneous curves were corrected manually via a software interface and integral values were calculated automatically using the device’s software. NAA, Co, and Cr peaks were included at approximately 2.02, 3.22 and 3.02 part per million (ppm), respectively.

Statistical EvaluationSPSS 20.0 software was used for statistical analysis and p<0.05

was considered as statistically significant. The distribution of numeric variables obtained by MRS was evaluated using histograms and the distribution was found as not normal. Therefore, the Kruskal-Wallis H test was run to determine whether there were differences between the three groups and the Mann-Whitney U test was used to determine differences between two groups. The strength and direction of the association between numeric variables and nominal and ordinal variables were performed using Spearman's rho test.

Results

Clinical FindingsThe mean ages of the groups were as follows: 34.6±12.5 years

(range, 22-52 years) in the ASE group (3 F, 1 M), 23.8±5.91 years (range, 16-33 years) in the GGE group (7 F, 3 M), and 30±11.65

years (range, 18-56 years) in the HC group (7 F, 3 M). Cranial images of all patients in the patient and control groups were within normal limits. Prognosis was significantly worse in the ASE group compared with the GGE group. The clinical characteristics of patients with ASE and GGE are shown in Table 1.

Magnetic Resonance Spectroscopy FindingsThe comparison of MRS metabolite levels of groups revealed

significant differences between frontal Co levels, Co/Cr ratios, NAA/Cr ratios, and thalamic NAA levels and NAA/Cr ratios (Tables 2, 3, Figure 2a). Frontal Co and Co/Cr levels were highest in the ASE group, followed by GGE and HC groups (Figure 2b). In contrast, NAA levels were lowest in the ASE group. NAA levels were a little higher in the GGE group than in the ASE group, but lower compared with the HC group. Thalamic NAA level and NAA/Cr ratio were statistically significantly lower in the ASE group compared with the GGE and HC groups in the between-group comparisons. These values were also found lower in the GGE group than in the HC, but the difference was not statistically significant. In addition, the frontal NAA levels and NAA/Cr ratio were lower in the ASE group compared with the HC group. Frontal Co levels and Co/Cr ratios were significantly higher in the ASE and GGE groups compared with the HC group. Although frontal Co levels and the Co/Cr ratio were higher in the ASE group compared with the GGE group, there was no statistically significant difference. The following correlations were found for the presence of ASE in patients with GGE: positive correlation (p=0.04, z=-0.549) with frontal Co/Cr ratio, negative correlation (p=0.016, z=-0.628) with frontal NAA/Cr ratio and negative correlation (p=0.002, z=-0.745) with the thalamic NAA/Cr ratio. There were negative correlations between the presence of absence seizures and the thalamic NAA/Cr ratio (p=0.009, z=-0.230) and thalamic NAA levels (p=0.004, z=-0.572). There were

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Figure 2. Different magnetic resonance spectroscopy metabolite levels between groups; a) Thalamic N-acetyl aspartate and N-acetyl aspartate/creatine levels were observed to be the lowest in the absence status epilepticus group, b) Frontal lobe choline and choline/creatine levels were increased in the absence status epilepticus group


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Table 1. The clinical characteristics of the patientsClinical characteristics ASE (n=4) GJE (n=10) Statistical resultsThe age of onset of epilepsy (years)* 19.38±13.889 (2-35) 13.35±5.764 (5-22) Not significant

The age of onset of ABS (years)* 20.88±18.984 (2-47) 14.58±8.357 (5-28)

The age of onset of MYC (years)* 23.33±10.116 (17-35) 14.67±5.465 (6-22) Not significant

The age of onset of GTCS (years)* 21.75±8.846 (17-35) 15.67±6.022 (6-22) Not significant

Duration of epilepsy (years)* 15.1±5.571 (7.7-20.9) 10.5±7.131 (1.8-23.8) Not significant

Family history of epilepsy (n/%)† 1 (25) 4 (40) Not significant

All seizure types (n/%)‡

MYC -- 1 (10)

Not significant

Absence -- 2 (20)

Absence+GTC -- 1 (10)

MYC+Absence -- 1 (10)

MYC+GTC -- 1 (10)

MYC+GTC+Absence 4 (100) 4 (40)

Initial MYC frequency (n/%)‡

≥30 per month 1 (10) 3 (30)

Not significant<30, ≥4 per month 1 (10) 4 (10)

<4 per month 2 (20) --

Recent MYC frequency (n/%)‡

≥30 per month - --

Not significant<30, ≥4 per month 2 (50) 2 (20)

<4 per month -- 1 (10)

None for at least 2 years 2 (50) 5 (50)

Initial GTCS frequency (n/%)‡

≥12 annually -- --

2-11 annually 1 (10) 3 (30)

<2 annually 3 (30) 3 (30) Not significant

Recent GTC frequency (n/%)‡

2-11 annually -- --

Not significant<2 annually -- --

None for 2 years 4 (100) 6 (60)

Initial ABS frequency(n/%)†

≥1 per week 2 (50) 4 (40)

<3 per month 2 (50) 3 (30) Not significant

Recent ABS frequency(n/%)‡

None for 4 years 1 (25) 6 (60)

Rare (1 per month) 1 (25) 1 (10) Not significant

≥1 per week 2 (50) --

Recent treatment (n/%)‡

VPA 3 (75) 4 (40)

LEV -- 3 (30) Not significant

VPA+LEV (25) 2 (20)

No medication 1 (10)

Prognosis† Good -- 8 (80)

Moderate 4 (100) 2 (20)

Refractory -- -- p=0.015

Syndrome (n/%)‡ CAE -- 1 (10)

p=0.021

JAE -- 2 (20)

JME 1 (25) 7 (70)

Atypical GGE with recurrent ASE 3 (75) --

*Mann-whitney u test, †Fisher’s exact test, ‡Pearson’s chi-square, ASE: Absence status epilepticus, CAE: Childhood absence epilepsy, GGE: Genetic generalized epilepsy, JAE: Juvenile absence epilepsy, JME: Juvenile myoclonic epilepsy, GTCS: Generalized tonic-clonic seizure, LEV: Levetiracetam, MYC: Myoclonus, VPA: Na-valproate


negative correlations between prognosis and thalamic NAA levels (p=0.026, z=-0.591) and the NAA/Cr ratio (p=0.013, z=-0.645).

Discussion

In several studies in few patients with GGE, thalamic NAA/Cr ratio has been found to be decreased in the patient groups compared with controls, thus demonstrating a disorder in thalamic neuronal metabolism, which supports the idea that the origin of the seizures is an abnormality in the thalamocortical network (19,20,21). In addition, in MRS studies, frontal lobe

NAA levels in patients with GGE have been found decreased compared with controls and prefrontal dysfunction has been shown particularly in GGE; the etiology of these neuronal-originated changes is not yet clear, but might be associated with regional possible cortical dysplasia at a microscopic level (14,15). In our study, the detection of decreases in NAA levels and NAA/Cr ratios in all patients with GGE that were significantly lower in patients with recurrent ASE compared with patients without ASE episodes suggests that recurrent ASE episodes are caused by more prominent thalamic dysfunction and neuronal loss when compared with HC using thalamic voxels. On the other hand, it

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Table 2. Magnetic resonance spectroscopy metabolite levels of the study groups

Group Minimum Maximum Mean Standard deviation

Control

Thalamic Co 6.11 11.60 8.6635 1.32422

Thalamic Cr 9.69 12.90 11.1245 0.90804

Thalamic Co/Cr 0.44 1.12 0.7772 0.15943

Thalamic NAA 20.30 29.30 25.8500 2.35674

Thalamic NAA/Cr 2.05 2.91 2.4013 0.25434

Frontal Co 4.75 9.72 7.5960 1.33113

Frontal Cr 8.18 11.90 10.2730 0.85248

Frontal Co/Cr 0.53 1.14 0.7480 0.14699

Frontal NAA 19.70 30.00 23.6750 2.65070

Frontal NAA/Cr 1.95 3.11 2.3265 0.27178

ASE

Thalamic Co 6.96 11.60 9.2237 1.63536

Thalamic Cr 10.20 12.00 11.1750 0.68817

Thalamic Co/Cr 0.59 0.97 0.8055 0.12707

Thalamic NAA 22.30 24.80 23.3250 1.00534

Thalamic NAA/Cr 1.92 2.21 2.0862 0.09319

Frontal Co 7.77 11.50 9.8863 1.45953

Frontal Cr 7.78 14.60 11.0225 2.26631

Frontal Co/Cr 0.68 1.20 0.9521 0.16855

Frontal NAA 17.90 26.60 21.4250 3.03962

Frontal NAA/Cr 1.49 2.43 1.9637 0.32820

GGE

Thalamic Co 7.16 11.10 9.1810 0.92088

Thalamic Cr 8.41 14.50 11.6905 1.54293

Thalamic Co/Cr 0.62 1.03 0.8034 0.11183

Thalamic NAA 22.30 28.40 25.2550 1.47772

Thalamic NAA/Cr 1.91 2.82 2.2890 0.24721

Frontal Co 6.97 9.83 8.7905 0.71335

Frontal Cr 7.75 13.40 10.2825 1.32039

Frontal Co/Cr 0.70 1.05 0.8568 0.09101

Frontal NAA 18.60 27.20 22.2900 2.86942

Frontal NAA/Cr 1.62 2.74 2.1885 0.29596ASE: Absence status epilepticus, GGE: genetic generalized epilepsy, Co: Choline, Cr: Creatinine, NAA: N-acetyl aspartate


is thought that recurrent ASE episodes might have caused this damage. At the same time, supporting the literature, similar findings, more prominent in patients with ASE episodes were detected in frontal cortex of all patients with GGE. However, the presence of both frontal cortical and thalamic prominent involvement in patients with ASE refers to a probable difference in thalamocortical cycle in the etiopathogenesis of recurrent ASE episodes or to the probability of occurrence of this dysfunction also as a result of episodes. In our study, the determination of a worse prognosis in these patients supports this theory. In studies of patients with frontal lobe epilepsy, the increase in Co and/or Cr levels was found more significant than the NAA decrease and this finding was thought to reflect high metabolic activity and/or gliosis in glial cells (20). In addition, a decrease in NAA level and increase in Co and Cr levels in MRS studies that examined temporal lobes were similarly found (12) and this increase was linked to gliosis, as these metabolites were found mostly in oligodendrocytes and astrocytes. In our study, the increase in mean frontal lobe Co and Co/Cr values in all patients with GGE, especially in those with recurrent ASE episodes compared with controls was more pronounced than NAA decrease. This led to the idea that the increase in frontal lobe Co levels and Co/Cr ratio may be a common finding in all patients with GGE and ASE episodes might be closely related to the decrease in NAA levels and NAA/Cr ratio. Detection of increased levels of glutamate, which causes an increase in neuronal excitability in the prefrontal cortex, also supports the notion of a frontal metabolic disorder and an increase in glutamatergic excitatory structures (14).

Conclusion

Although we had few patients due to the rarity of this disease, frontal lobe and thalamic neurochemical disorders detected in all patients with GGE suggest a thalamocortical network disorder in the etiopathogenesis of ASE. In addition, the more pronounced neurochemical disorder in patients with recurrent

ASE episodes gave the impression that ASE episodes might be of thalamocortical network origin and these episodes might increase the existing damage involved in the pathogenesis. However, these findings should be supported by further studies including more patients with recurrent ASE episodes and/or implementation of new imaging methods.

Ethics

Ethics Committee Approval: The study was approved by the İstanbul University Ethics Committee.

Informed Consent: Consent form was filled out by all participants.Peer-review: Externally peer-reviewed.


Medical Practices: Zeynep Aydın Özemir, Betül Baykan, Ebru Nur Vanlı Yavuz, Concept Zeynep Aydın Özemir, Ebru Nur Vanlı Yavuz, Design: Zeynep Aydın Özemir, Data Collection or Processing: Zeynep Aydın Özemir, Analysis or Interpretation: Zeynep Aydın Özemir, Serra Sencer, Betül Baykan, Literature Search: Zeynep Aydın Özemir, Ebru Nur Vanlı Yavuz, Writing: Zeynep Aydın Özemir.

Conflict of Interest: No conflict of interest was declared by the authors.Financial Disclosure: This study received financial support from the

İstanbul University Scientific Research Projects Foundation (number: T-391/08032004).

References1. Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, Shorvon

S, Lowenstein DH. A definition and classification of status epilepticus- Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia 2015;56:1515-1523.

2. Betjemann JP, Lowenstein DH. Status epilepticus in adults. The Lancet Neurology 2015;14:615-624.

3. Cascino GD. Nonconvulsive status epilepticus in adults and children. Epilepsia 1993;34:21-28.

4. Shorvon S, Trinka E. The 5th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures. Epilepsy Behav 2015;49:1-3.

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Table 3. Significant within-group and between-group values

Metabolites measured by MRS

The comparison of all groups*

ASE† GJE†

GGE Healthy controls

Healthy controls

Thalamic

Co Not significant Not significant Not significant Not significant

Cr Not significant Not significant Not significant Not significant

Co/Cr Not significant Not significant Not significant Not significant

NAA p=0.006 p=0.003 p=0.003 Not significant

NAA/Cr p=0.006 p=0.02 p=0.002 Not significant

Frontal lobe

Co p=0.001 Not significant p=0.001 p=0.004

Cr Not significant Not significant Not significant Not significant

Co/Cr p=0.001 Not significant p=0.003 p=0.004

NAA Not significant Not significant p=0.04 Not significant

NAA/Cr p=0.04 Not significant p=0.02 Not significant*Kruskal-wallis test, †Mann-whitney u test, ASE: Absence status epilepticus, GGE: Genetic generalized epilepsy, Co: Choline, Cr: Creatinine, NAA: N-acetyl aspartate


5. Naylor DE, Liu H, Niquet J, Wasterlain CG. Rapid surface accumulation of NMDA receptors increases glutamatergic excitation during status epilepticus. Neurobiol Dis 2013;54:225-238.

6. Cock HR, Tong X, Hargreaves IP, Heales SJ, Clark JB, Patsalos PN, Thom M, Groves M, Schapira AHV, Shorvon SD, Walker MC. Mitochondrial dysfunction associated with neuronal death following status epilepticus in rat. Epilepsy Res 2002;48:157-168.

7. David Y, Cacheaux LP, Ivens S, Lapilover E, Heinemann U, Kaufer D, Friedman A. Astrocytic dysfunction in epileptogenesis: Consequence of altered potassium and glutamate homeostasis? J Neurosci 2009;29:10588-10599.

8. Friedman A, Dingledine R. Molecular cascades that mediate the influence of inflammation on epilepsy. Epilepsia 2011;52:33-39.

9. Marchi N, Granata T, Freri E, Ciusani E, Ragona F, Puvenna V, Teng Q, Alexopolous A, Janigro D. Efficacy of anti-inflammatory therapy in a model of acute seizures and in a population of pediatric drug resistant epileptics. PLoS One 2011;28:e18200.

10. Urenjak J, Williams SR, Gadian DG, Noble M. Proton nuclear magnetic resonans spectroscopy unambiguously identifies different neural cell types. J Neuroscience 1993;13:981-999.

11. Bjartmar C, Battistuta J, Terada N, Dupree E, Trapp BD. N-acetylaspartate is an axon-specific marker of mature white matter in vivo: A biochemical and immunohistochemical study on the rat optic nerve. Ann Neurology 2002;51:51-58.

12. Bernasconi A, Tasch E, Cendes F, Li LM, Arnold DL. Proton magnetic resonance spectroscopic imaging suggests progressive neuronal damage in human temporal lobe epilepsy. Prog Brain Res 2002;135:297-304.

13. De Stefano N, Matthews PM, Arnold DL. Reversible decreases in N-acetylaspartate after acute brain injury. Magn Reson Med 1995;34:721-727.

14. Simister RJ, McLean MA, Barker GJ, Duncan JS. Proton MRS reveals frontal lobe metabolite abnormalities in idiopathic generalized epilepsy. Neurology 2003;61:897-902.

15. Savic I, Lekvall A, Greitz D, Helms G. MR spectroscopy shows reduced frontal lobe concentrations of N-acetyl aspartate in patients with juvenile myoclonic epilepsy. Epilepsia 2000;41:290-296.

16. Bernasconi A, Bernasconi N, Natsume J, Antel SB, Andermann F, Arnold DL. Magnetic spectroscopy and imaging of the thalamus in idiopathic generalized epilepsy. Brain 2003;126:2447-2454.

17. Mory SB, Li LM, Guerreiro CAM, Cendes F. Thalamic dysfunction in juvenile myoclonic epilepsy: A proton MRS Study. Epilepsia 2003;44:1402-1405.

18. Shorvon SD. The etiologic classification of epilepsy. Epilepsia 2011;52:1052-1057.

19. Savic I, Osterman Y, Helms G. MRS shows syndrome differentiated metabolite changes in human-generalized epilepsies. Neuroimage 2004;21:163-172.

20. Lundbom N, Gaily E, Vuori K, Paetau R, Liukkonen E, Rajapakse JC, Valanne L, Hakkiken AM, Granström ML. Proton spectroscopic imaging shows abnormalities in glial and neuronal cell pools in frontal lobe epilepsy. Epilepsia 2001;42:1507-1514.

21. Cendes F, Caramanos Z, Andermann F, Dubeau F, Arnold DL. Proton magnetic resonance spectroscopic imaging and magnetic resonance imaging volumetry in the lateralization of temporal lobe epilepsy: A series of 100 patients. Ann Neurology 1997;42:737-746.

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Ad dress for Cor res pon den ce/Ya z›fl ma Ad re si: Ebru Nur Vanlı Yavuz MD, İstanbul University İstanbul Faculty of Medicine, Department of Neurology, Division of Clinical Neurophysiology, İstanbul, Turkey


Objective: Hippocampal sclerosis (HS) is usually associated with typical anterior temporal spikes/sharp waves in the electroencephalography (EEG). We aimed to investigate the clinical, electrophysiologic differences, and prognosis between HS patients with unusual epileptic foci in comparison with patients with typical foci.

Materials and Methods: Patients diagnosed who were diagnosed as having mesial temporal lobe epilepsy with HS in our center were included. All magnetic resonance imaging (MRI) results were investigated for the presence of two major criteria of HS diagnosis, namely T1 atrophy and T2 hyperintensity. All EEG and video-EEG investigations (a total of 496) were re-evaluated for unusual epileptic activities except T1/2, F7/8, T3/4 foci. Clinical and other laboratory data were retrospectively reevaluated by two investigators and the groups with usual and unusual epileptic activities for this syndrome were statistically compared.

Results: A total of 124 patients including 20 (16.1%) with unusual epileptic activities (group 1) and 104 patients with typical foci (group 2) were evaluated. We observed 11 posterior temporal (T5/T6), four frontal (F3/F4), four frontopolar (Fp1/2), two occipital (O1/O2), three central (CP/FC) unusual foci, and two generalized epileptiform discharges in these 20 patients. Impaired background activity, nonspecific interictal diffuse slowing, and atypical seizure offset patterns were more frequently observed in group 1. Forty-nine patients underwent surgery after appropriate preoperative diagnostics; there was no significant difference in the postoperative outcome between the groups despite a tendency to better prognosis in group 2.

Conclusion: Our study showed that unusual epileptic foci could be seen in 16.1% of patients with HS. Although some patients with HS have these atypical interictal EEG findings, they might obtain good post-operative outcomes when preoperative diagnostics are appropriately planned.

Keywords: Mesial temporal lobe epilepsy, hippocampal sclerosis, electroencephalography, prognosis

Amaç: Hipokampal skleroz (HS) genelde elektroensefalografide (EEG) ön temporal elektrotlarda görülen tipik dikenler/keskin dalgalar ile ilişkilidir. Çalışmada bu odaklardan farklı lokalizasyonlarda epileptik odakların ve aktivitelerin görüldüğü olguların, tipik odakları olanlara kıyasla klinik, elektrofizyolojik özelliklerinin ve prognoz farklarının araştırılması amaçlanmıştır.

Gereç ve Yöntem: Merkezimizde mezyal temporal lob epilepsisi ile giden HS tanısıyla takipli olgular çalışmaya dahil edildi. Tüm manyetik rezonans görüntülemeler (MRG) iki ana HS tanı kriterinin (hipokampal yapılarda atrofi ve T2 ya da FLAIR sekanslarında sinyal artışı) varlığı açısından incelendi. Tüm EEG ve video EEG incelemeleri (toplam 496 adet) T1/2, F7/8, T3/4 odakları dışında farklı bir alanda epileptik aktivitesi olan ve olmayan hastalar açısından incelendi. Klinik ve diğer laboratuvar incelemeleri iki araştırmacı tarafından retrospektif olarak değerlendirildi. Olağan dışı odağı olan hastalarla olağan dışı odağı olmayan hastalar istatistiksel yöntemlerle kıyaslandı.

Bulgular: Yirmisinde olağan dışı (%16,1) epileptik aktivite olan (grup 1), 104’ünde ise olağan dışı epileptik aktivite olmayan (grup 2) toplam 124 hasta çalışmaya dahil edildi. Olağan dışı epileptik aktivitelerden on biri posterior temporal (T5/T6), dördü frontal (F3/F4), dördü frontopolar (Fp1/Fp2), ikisi oksipital

Investigation of Patients with Hippocampal Sclerosis Associated with Unusual Epileptic Activities

Hipokampal Skleroz Olgularında Olağan Dışı Epileptik Aktivitelerin Araştırılması

Ebru Nur Vanlı Yavuz, Hakan Yener, Zeynep Aydın Özemir, Nerses Bebek, Candan Gürses, Ayşen Gökyiğit, Betül Baykanİstanbul University İstanbul Faculty of Medicine, Department of Neurology, Division of Clinical Neurophysiology, İstanbul, Turkey

Sum mary

Öz

67

Turk J Neurol 2016;22:67-72 Vanlı Yavuz et. al.; Unusual Epileptic Activities of Hippocampal Sclerosis

Introduction

One of the most important causes of drug-resistant focal epilepsies is mesial temporal lobe epilepsy (MTLE). Histopathologically, MTLE is known to be associated with hippocampal sclerosis (HS) (1,2,3). Magnetic resonance imaging (MRI) has been shown to be a highly sensitive diagnostic method in HS diagnosis and with 3T MRI, the rate of HS in patients with MTLE reaches nearly 28% (4). Although there are patients with HS who are responsive to anti-epileptic drugs (AED), most patients in this group are AED resistant. Many previous studies have demonstrated that 40-90% of patients become epilepsy-free after well-planned surgeries (5,6). Inter-ictal and ictal electroencephalography (EEG) records are very useful in the pre-surgical evaluation of AED- resistant patients. Patients with HS EEG may be normal or show characteristic findings. Spikes, sharp waves, and sharp and slow wave complexes in anterior temporal electrodes are typical epileptiform findings of inter-ictal EEG. The findings may be unilateral, bilateral, isolated, independent from each other or synchronized. In characteristic EEG, the maximum potential is seen in sphenoidal, T1/2, and/or frontotemporal (F7/8, T3/T4) electrodes (7). In addition, different epileptic activities are sometimes detected in inter-ictal EEGs. In resistant patients whose inter-ictal EEG, clinical, and cranial MRI findings are consistent with HS, the next step is lateralization and localization of the seizure (8,9). Sometimes the result of this diagnostic examination is unsuccessful despite performing all evaluations appropriately, the reasons for this failure are not clearly known. The aim of our study was to compare the clinical, electrophysiologic, and prognostic features of patients with unusual epileptic foci or activities with those with typical epileptic foci or activities.


Patient Selection This study included patients temporal lobe epilepsy, who

were being treated by the Neurology Department of İstanbul University İstanbul Faculty of Medicine, and came for a follow-up visit between 2013 and 2014 and had at least one EEG evaluation. The study protocol was approved by the ethics committee of İstanbul University Faculty of Medicine and the patients were included after they signed informed consent forms. Available MRI scans were reevaluated. Atrophy of hippocampal structures and increased signal intensity in T2 or FLAIR sequences in scans that were performed under standard epilepsy protocol using a 1.5 tesla (T) MRI device were reviewed (9,10). 3T MRI was performed in patients with indeterminate HS. After MRI evaluations, patients with dual pathologies underwent surgery but patients whose pathology results were not consistent with HS or patients whose

HS diagnosis could not be confirmed with MRI were excluded. 3T MRI was performed in seven patients to obtain a definite diagnosis, three of which were detected to have bilateral HS. Demographic and clinical data such as age, duration of follow-up, age of first seizure, presence of bilateral or a unilateral HS, history of status epilepticus, drug resistance, presence of mental retardation, febrile seizure, febrile status epilepticus, or familial history of epilepsy were recorded on a standard form. Seizure semiology and syndrome classification were performed in accordance with the International League Against Epilepsy (ILAE) criteria (11). The patients’ auras were evaluated in accordance with ILAE terminology (12). Patients whose seizures persisted despite mono- or combined treatment with 2 AEDs were defined as ‘resistant epilepsy’ (13). Postoperative epilepsy status was determined in accordance with the Engel classification (14). Febrile status epilepticus was defined as a seizure in a neurologically-normal child aged 6-50 months of more than 30 minutes duration that did not originate from the central nervous system (15). Diagnosis of mental retardation was made clinically or during a neuropsychometric test. Patients were called by telephone in the event that their data were incomplete.

Electrophysiologic Assessments All available electrophysiologic findings (routine EEG, long-

term video-EEG monitoring (VEM), and invasive EEG) were independently evaluated by 2 epileptologists at different times. The following were reviewed and recorded using a standard form: basic activity failure in inter-ictal EEG records; temporal intermittent rhythmic delta activity; frontal intermittent rhythmic delta activity (16); inter-ictal nonspecific slowing (generalized or regional slowing) and increase in epileptic activity during hyperventilation; intermittent photic stimulation and sleep; seizure initiation pattern in ictal EEG records (unilateral or bilateral); seizure initiation rhythm (theta or delta); dominant seizure rhythm (theta, delta, alpha or fast rhythm); and seizure ending rhythm (theta, delta, alpha, or fast rhythm). All EEG activities were evaluated, and the patients were then classified as those with or without epileptic foci outside T1/2, F7/8, T3/4 (groups 1 and 2, respectively).

Statistical AnalysisSPSS 20.0 package program was used for statistical evaluation

and p<0.05 was accepted as the limit for significance. Descriptive analyses and Chi-square test or Fisher’s exact test for between-group analyses were used.

Results

This study included a total of 124 patients (49 women and 75 men) who met the study criteria including confirmation of HS

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(O1/O2), üçü santral (CP/FC) lokalizasyonluydu ve iki hastada ise jeneralize epileptiform deşarjlar izlendi. Temel aktivite yetersizliği, interiktal nonspesifik yaygın yavaşlama, atipik nöbet sonlanma paterni grup 1’de anlamlı olarak fazla bulundu. Uygun preoperatif cerrahi hazırlık sonrası 49 hasta ameliyat olmuştu ve grup 2 de cerrahi sonrası daha iyi prognoza eğilim olsa da her iki grup arasında ameliyat sonrası prognoz açısından anlamlı farklılık yoktu.

Sonuç: Çalışmamız HS olgularında %15,9 oranında olağan dışı epileptik odakların görülebildiğine dikkat çekmiştir. Bazı HS olguları bu atipik interiktal EEG bulgularını göstermekle birlikte, uygun şekilde preoperatif incelemeleri yapıldığında, iyi post-operatif prognoz gösterebilmektedir.

Anahtar Kelimeler: Mezyal temporal lop epilepsisi, hipokampal skleroz, elektroensefalografi, prognoz

Turk J Neurol 2016;22:67-72Vanlı Yavuz et. al.; Unusual Epileptic Activities of Hippocampal Sclerosis

diagnoses. A patient whose MRI findings were consistent with HS during follow-ups but postsurgical pathologic evaluation was not consistent with HS was excluded. Two independent senior electrophysiologists reviewed 389 routine EEG recordings with a total duration of 14394.5 hours, 109 VEM, 12 invasive EEGs, and 416 ictal records. There were 20 patients with unusual interictal epileptic activities (group 1), and 104 patients with typical epileptic activities (group 2). Figure 1, 2 shows examples of the patients’ typical and unusual epileptic activities. Unusual foci were detected in 1 area in ten patients, and in at least 2 different areas in 10 patients. Among them, 110 EEG evaluations (85 routines, 23 VEM, 2 invasive) belonged to the unusual epileptic activity group. Among unusual epileptic activities, 11 were at T5/T6, 4 were at Fp1/Fp2, 2 were at O1/O2, and 3 were at CP/FC. Generalized epileptic activity was observed in two patients. Among the 20 patients with unusual foci, nine were men and 11

women. Eight (40%) patients were diagnosed as having bilateral HS. All patients except three (13%) were treatment resistant. No statistically significant difference was detected between groups with regards to clinical features and semiologic findings. There was a statistically significant difference between groups according to basic activity failure, inter-ictal nonspecific slowing, and seizure ending pattern (p=0.003, p=0.024, and p=0.048, respectively). Forty-nine of the patients had undergone previous surgeries: 17 for right HS, 23 for left HS, and 9 for bilateral HS. It was striking that there was no difference between the groups according to duration of epilepsy-free periods after surgery. Table 1 demonstrates the detailed clinical, electrophysiologic, and postoperative results of groups 1 and 2.

Discussion

In our study, unusual epileptic activity in addition to foci that are expected in patients with MTLE-HS were detected in 16.1% of all patients with HS. Similar to our study, the rate of lateral temporal and extra-temporal foci was found as 17.7% in patients with amygdala lesions and 20% in individuals with MTLE-HS who were included as a control group (17). Unusual foci are located at different places and the features of the patients do not indicate a specific sub-type. A comparison of an AED-resistant MTLE group with a non-resistant group showed that inter-ictal epileptic or nonspecific anomalies have an effect on prognosis (18,19). However, in our study it was interesting that there was no difference between groups according to prognosis or drug resistance despite a difference in basic activity failure, nonspecific anomaly or seizure type. When inter-ictal foci are multifocal or bilateral they may negatively affect seizure control in the postoperative period. On the other hand, no difference was found according to seizure control.

In summary, the effects of inter-ictal findings in prognosis are still controversial (20,21). In accordance with the findings of our study, inter-ictal spikes originate from neocortical structures instead of mesial temporal structures and noninvasive EEG does

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Figure 1a, 1b. Classical and unusual samples of epileptic activity, 1a) F8 focus, 1b) Fp1 focus in the same patient

Figure 2. Generalized epileptic activity during intermittent photic stimulation


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Table 1. The clinical, electrophysiological and postoperative comparisons of groups 1 and 2

Grup 1 (n=20)

Grup 2 (n=104)

Statistical significance

Current age, years, mean (SD) 34.45 (6.48) 39.06 (11.10) Not significant

Follow-up duration, months, mean (SD) 97.00 (61.33) 94.63 (87.42) Not significant

Male/female, n 9/11 40/64 Not significant

Age at seizure onset, years, mean (SD) 13.90 (9.90) 13.25 (11.39) Not significant

Bilateral HS, n (%) 8 (40.0) 23 (22.1) Not significant

Status epilepticus, n (%) 5 (25.0) 14(13.5) Not significant

Drug resistance, n (%) 17 (85.0) 85 (81.7) Not significant

Mental retardation, n (%) 4 (20.0) 17 (16.3) Not significant

History of febrile seizure 15 (75.0) 65 (62.5) Not significant

History of febrile status epilepticus, n (%) 5 (25.0) 14 (14.1) Not significant

Family history of epilepsy, n (%) 6 (30.0) 29 (27.9) Not significant

EEGImpaired background activity, n (%)* 5 (25.0) 3 (2.9) <0.003*

TIRDA, n (%) 3 (15.0) 32 (30.8) Not significant

FIRDA, n (%) 13 (65.0) 44 (73.3) Not significant

Interictal nonspecific slowing, n (%)*DiffuseRegionalAbsent

9 (45.0)9 (45.0)2 (10.0)

18 (17.3)59 (56.7)27 (26.0)

0.024**

Activation of foci during HV, n (%) 3 (15.0) 20 (19.2) Not significant

Activation of foci during IPS, n (%) 1 (5.0) 1 (1.0) Not significant

Activation of foci during sleep, n (%) 2 (10.0) 22 (21.2) Not significant

Ictal EEG: 109 VEM in 79 patients***Unilateral seizure onset, n (%)Bilateral seizure onset, n (%)Undetermined seizure onset, n (%)

9 (64.3)1 (7.1)4 (28.6)

38 (66.7)4 (7.0)15 (26.3)

Not significant

Seizure onset pattern, n (%)Rhythmic theta, n (%)Rhythmic delta, n (%) Other (undetermined or suppression), n (%)

5 (35.7)1 (7.1)8 (57.1)

32 (56.1)3 (5.3)22 (38.6)

Not significant

Dominant seizure rhythm, n (%)Rhythmic theta, n (%)Rhythmic delta, n (%)Other (alpha/fast activity, n (%)

12 (85.7)1 (7.1)1 (7.1)

47 (82.5)3 (5.3)7 (12.3)

Not significant

Seizure offset pattern, n (%)Rhythmic theta, n (%)Rhythmic delta, n (%)Other (alpha/fast activity), n (%)

1 (7.1)7 (50.0)6 (42.9)

8 (14.0)42 (73.7)7 (12.3)

0.048**

Total operated patients, n (%) 9 (45.0) 40 (42.5) Not significant

Postoperative follow up duration, years, mean (SD)

3.00 (3.36) 3.92 (3.05) Not significant

Engel I/II-IV classification, n 6/3 36/4 Not significant

EEG: Electroencephalography, SD: Standard deviation, HS: Hippocampal sclerosis, n: Number, TIRDA: Temporal intermittent rhythmic delta activity, FIRDA: Frontal intermittent rhythmic delta activity, HV: Hyperventilation, IPS: Intermittent photic stimulation, VEM: Video-electroencephalography monitoring, *Chi-square test, **Fisher’s exact test, ***Five patients data was unavailable, three patient did not have seizure during video electroencephalography

Turk J Neurol 2016;22:67-72Vanlı Yavuz et. al.; Unusual Epileptic Activities of Hippocampal Sclerosis

not have a good localizing effect (22). A study by Pittau et al in a group of AED resistant and non-resistant patients showed that different inter-ictal EEG findings have adverse effects on prognosis (18). We mostly chose our patients from the AED-resistant group because our center is a tertiary level epilepsy center. If we had studied a group with less resistant patients, our findings about inter-ictal unusual epileptic activities might have changed and its effects on prognosis might have been different. Although the underlying mechanism of atypical inter-ictal foci is not known, it can be speculated that dysplasia at the microscopic level that cannot be detected in MRI may be causative. The greater impairment of basic activity in this group and relatively more frequent presence of inter-ictal nonspecific slow waves suggest an initial precipitating event (birth trauma, head trauma or silent limbic encephalitis), which causes more global impairment. There are studies that claimed absence of a negative impact of dual pathology in patients with anterior temporal lobectomy and selective amygdalohippocampectomy (23,24,25). Another study found that bilateral amygdalohippocampal atrophy was common in temporal lobe developmental anomalies and negatively affected prognosis (26). Although we excluded dual pathology in our study with MRI, we selected patients who met 1.5T MRI criteria. However, if we could have investigated with different and more sensitive diagnostic methods we would have seen comorbid dual or other pathologies. A higher frequency of patients with HS among our group with usual foci was noticeable; however, it did not reach statistical significance. In two patients with generalized type and photosensitive epileptiform anomalies, it was controversial as to whether this clinical picture was a comorbid genetic syndrome or a fast secondary bilateral hypersynchronization. We do not have information such as invasive EEG, history of epilepsy in the family, and detection of mutations to definitely diagnose these patients.

Conclusion

In conclusion, atypical inter-ictal epileptiform anomalies have been detected in some patients. Although this was a heterogeneous group, the rate of epilepsy-free patients was not different from those with typical inter-ictal EEG findings with good pre-surgical planning.

Ethics

Ethics Committee Approval: The study were approved by the İstanbul University İstanbul Faculty of Medicine of Local Ethics Committee.



Surgical and Medical Practices: Nerses Bebek, Candan Gürses, Ayşen Gökyiğit, Betül Baykan, Concept: Ebru Nur Vanlı Yavuz, Design: Ebru Nur Vanlı Yavuz, Betül Baykan, Data Collection or Processing: Ebru Nur Vanlı Yavuz, Hakan Yener, Zeynep Aydın Özemir, Analysis or Interpretation: Ebru Nur Vanlı Yavuz, Betül Baykan, Literature Search: Ebru Nur Vanlı Yavuz, Writing: Ebru Nur Vanlı Yavuz, Zeynep Aydın Özemir, Betül Baykan.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

References1. Blümcke I, Thom M, Aronica E, Armstrong DD, Bartolomei F, Bernasconi

A, Bernasconi N, Bien CG, Cendes F, Coras R, Cross JH, Jacques TS, Kahane P, Mathern GW, Miyata H, Moshé SL, Oz B, Özkara Ç, Perucca E, Sisodiya S, Wiebe S, Spreafico R. International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: a Task Force Report from the ILAE Commission on Diagnostic Methods. Epilepsia 2013;54:1315-1329.

2. Cendes F, Sakamoto AC, Spreafico R, Bingaman W, Becker AJ. Epilepsies associated with hippocampal sclerosis. Acta Neuropathol 2014;128:21-37.

3. Du X, Usui N, Terada K, Baba K, Matsuda K, Tottori T, Inoue Y. Semiological and electroencephalographic features of epilepsy with amygdalar lesion. Epilepsy Res 2015;111:45-53.

4. Coan AC, Kubota B, Bergo FP, Campos BM, Cendes F. 3T MRI quantification of hippocampal volume and signal in mesial temporal lobe epilepsy improves detection of hippocampal sclerosis. AJNR Am J Neuroradiol 2014;35:77-83.

5. Yasuda CL, Tedeschi H, Oliveira EL, Ribas GC, Costa AL, Cardoso TA, Montenegro MA, Guerreiro CA, Guerreiro MM, Li LM, Cendes F. Comparison of short-term outcome between surgical and clinical treatment in temporal lobe epilepsy: a prospective study. Seizure 2006;15:35-40.

6. Wiebe S, Blume WT, Girvin JP, Eliasziw M; A randomized, controlled trial of surgery for temporal-lobe epilepsy. Effectiveness and Efficiency of Surgery for Temporal Lobe Epilepsy Study Group. N Engl J Med 2001;345:311-318.

7. Blume WT. The necessity for sphenoidal electrodes in the presurgical evaluation of temporal lobe epilepsy: con position. J Clin Neurophysiol 2003;20:305-310.

8. Rosenow F, Lüders H. Presurgical evaluation of epilepsy. Brain 2001;124:1683-700.

9. Sirin NG, Gurses C, Bebek N, Dirican A, Baykan B, Gokyigit A. A quadruple examination of ictal EEG patterns in mesial temporal lobe epilepsy with hippocampal sclerosis: onset, propagation, later significant pattern, and termination. J Clin Neurophysiol 2013;30:329-338.

10. Cendes F, Andermann F, Gloor P, Evans A, Jones-Gotman M, Watson C, Melanson D, Olivier A, Peters T, Lopes-Cendes I. MRI volumetric measurement of amygdala and hippocampus in temporal lobe epilepsy. Neurology 1993;43:719-725.

11. Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, Engel J, French J, Glauser TA, Mathern GW, Moshé SL, Nordli D, Plouin P, Scheffer IE. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 2010;51:676-685.

12. Blume WT, Lüders HO, Mizrahi E, Tassinari C, van Emde Boas W, Engel J Jr. Glossary of descriptive terminology for ictal semiology: report of the ILAE task force on classification and terminology. Epilepsia 2001;42:1212-1218.

13. Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, Moshé SL, Perucca E, Wiebe S, French J. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 2010;51:1069-1077.

14. Wieser HG, Blume WT, Fish D, Goldensohn E, Hufnagel A, King D, Sperling MR, Lüders H, Pedley TA. ILAE Commission Report. Proposal for a new classification of outcome with respect to epileptic seizures following epilepsy surgery. Epilepsia 2001;42:282-286.

15. Scott RC, King MD, Gadian DG, Neville BG, Connelly A. Hippocampal abnormalities after prolonged febrile convulsion: a longitudinal MRI study. Brain 2003;126:2551-2557.

16. Brigo F. Intermittent rhythmic delta activity patterns. Epilepsy Behav 2011;20:254-256.

17. Du X, Usui N, Terada K, Baba K, Matsuda K, Tottori T, Inoue Y. Semiological and electroencephalographic features of epilepsy with amygdalar lesion. Epilepsy Res 2015;111:45-53.

18. Pittau F, Bisulli F, Mai R, Fares JE, Vignatelli L, Labate A, Naldi I, Avoni P, Parmeggiani A, Santucci M, Capannelli D, Di Vito L, Gambardella A, Baruzzi A, Tinuper P. Prognostic factors in patients with mesial temporal lobe epilepsy. Epilepsia 2009;50:41-44.

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19. Sànchez J, Centanaro M, Solís J, Delgado F, Yepez L. Factors predicting the outcome following medical treatment of mesial temporal epilepsy with hippocampal sclerosis. Seizure 2014;23:448-453.

20. Schulz R, Lüders HO, Hoppe M, Tuxhorn I, May T, Ebner A. Interictal EEG and ictal scalp EEG propagation are highly predictive of surgical outcome in mesial temporal lobe epilepsy. Epilepsia 2000;41:564-570.

21. Malter MP, Bahrenberg C, Niehusmann P, Elger CE, Surges R. Features of scalp EEG in unilateral mesial temporal lobe epilepsy due to hippocampal sclerosis: Determining factors and predictive value for epilepsy surgery. Clin Neurophysiol 2015;127:1081-1087.

22. Wennberg R, Valiante T, Cheyne D. EEG and MEG in mesial temporal lobe epilepsy: where do the spikes really come from? Clin Neurophysiol 2011;122:1295-1313.

23. Prayson BE, Prayson RA, Kubu CS, Bingaman W, Najm IM, Busch RM. Effects of dual pathology on cognitive outcome following left anterior temporal lobectomy for treatment of epilepsy. Epilepsy Behav 2013;28:426-431.

24. Savitr Sastri BV, Arivazhagan A, Sinha S, Mahadevan A, Bharath RD, Saini J, Jamuna R, Kumar JK, Rao SL, Chandramouli BA, Shankar SK, Satishchandra P. Clinico-pathological factors influencing surgical outcome in drug resistant epilepsy secondary to mesial temporal sclerosis. J Neurol Sci 2014;340:183-190.

25. Varoglu AO, Saygi S, Acemoglu H, Ciger A. Prognosis of patients with mesial temporal lobe epilepsy due to hippocampal sclerosis. Epilepsy Res 2009;85:206-211.

26. Kuzniecky R, Ho SS, Martin R, Faught E, Morawetz R, Palmer C, Gilliam F. Temporal lobe developmental malformations and hippocampal sclerosis: epilepsy surgical outcome. Neurology 1999;52:479-484.

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Ad dress for Cor res pon den ce/Ya z›fl ma Ad re si: Hakan Ahmet Ekmekçi MD, Selçuk University Faculty of Medicine, Department of Neurology, Konya, Turkey Phone: +90 532 155 16 50 E-mail: [email protected]

Re cei ved/Ge lifl Ta ri hi: 28.11.2015 Ac cep ted/Ka bul Ta ri hi: 06.03.2016This study was presented as a poster in 51th National Neurology Congress (27 November-3 December 2015, Antalya).

Objective: Hyperemesis gravidarum (HG) is a disease characterized by excessive vomiting and nausea during pregnancy. It differs from normal pregnancy where simple nausea and vomiting are seen frequently with unknown cause. The place and role of the brain in HG is unknown.

Materials and Methods: Thirty-three healthy pregnant women and 30 patients diagnosed with HG admitted to Selçuk University Faculty of Medicine, Obstetrics and Gynecology Department were included and electroencephalograph (EEG) signals of all patients obtained at Neurology Department were examined. These signals were evaluated with high math and examined with developed engineering methods. The sampling frequency of the EEG was 200 Hz. Data were obtained in the frequency-power axis using 0.1 Hz frequency resolution, Hamming windowing, and 0.5 overlap ratio with signals on the time axis on all channels. All sub-bands have formed with unearthed power spectral density as delta, theta, alpha, and beta and after being created was calculated spectral densities.

Results: As a result, while showing significant changes as delta band for Fp1F3, theta band for C3P3, F3C3, Fp1F3, P3O1, T5O1, for other channels and sub-bands has not seen any significant changes with regard to average power spectral density.

Conclusion: HG and normal pregnancies, when examined in terms of power spectral density, abnormalities were observed in the EEG signals in the left hemisphere frontal area of the delta band, fronto-centro-parietal, and parietal-occipital areas of the theta band. In light of the literature, neither cerebral abnormalities in HG could be displayed nor the place of abnormality could be shown. However, this study is the first to clearly show abnormalities of theta-delta band activity and differences of locations in the left cerebral hemisphere.

Keywords: Hyperemesis gravidarum, pregnancy, electroencephalograph, spectral power density

Amaç: Hiperemezis gravidarum (HG) hamilelik sırasında aşırı kusma ve bulantının ortaya çıkardığı bir hastalıktır. Normal gebelikte sıklıkla görülen basit bulantı ve kusmadan farklı olarak sebebi tam olarak bilinmeyen bir durumdur. Beynin HG’deki yeri ve rolü tam bilinmemektedir.

Gereç ve Yöntem: Selçuk Üniversitesi Tıp Fakültesi, Kadın Doğum Polikliniği’ne başvuran HG tanısı alan takipli 30 hastanın ve 33 normal gebenin hamilelik dönemlerine göre Nöroloji Anabilim Dalı’nca elde edilen elektroensefalografi (EEG) sinyalleri incelenmiştir. Bu sinyaller, yüksek matematik ve gelişmiş mühendislik yazılımları ile irdelenmiştir. EEG örnekleme frekans 200 Hz’dir. Tüm kanallarda bulunan zaman eksenindeki sinyaller Welch yöntemi ile 0,1 Hz frekans çözünürlüğü, Hamming pencereleme ve 0,5 örtüşme oranı kullanarak frekans-güç ekseninde veriler elde edilmiştir. Ortaya çıkarılan güç spektral

Hyperemesis Gravidarum and Cerebral Electrophysiology Determination of Cerebral Localization through

Electroencephalography Signal ProcessingHiperemezis Gravidarum ve Serebral Elektrofizyoloji: Elektroensefalografi Sinyal İşleme

Yöntemi ile Serebral Lokalizasyon Belirleme

Hakan Ahmet Ekmekçi1, Arzu Setenay Yılmaz2, Muhammet Üsame Öziç3, Yüksel Özbay3, Özlem Seçil Kerimoğlu2, Çetin Çelik2, Şerefnur Öztürk1

1Selçuk University Faculty of Medicine, Department of Neurology, Konya, Turkey2Selçuk University Faculty of Medicine, Department of Obstetrics and Gynecology, Konya, Turkey

3Selçuk University Faculty of Engineering, Electrical and Electronics Engineering, Konya, Turkey

Sum mary

Öz

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Turk J Neurol 2016;22:73-79 Ekmekçi et. al.; Cerebral Localization in Hyperemesis Gravidarum

Introduction

Nausea-vomiting is a common problem of pregnancy, during which significant metabolic and physiologic changes occur. It has biologic, pharmacologic, psychologic, and behavioral aspects. Nausea-vomiting during pregnancy is considered as a routine part of pregnancy and generally people do not put an emphasis on it (1). The basic neural pathway of nausea-vomiting uses the autonomic nervous pathway. Nausea, vomiting, and gagging have different causes (2). Unlike a simple reflex activity, what causes vomiting, how and at which severity vomiting occurs, and the threshold value for vomiting are very complex and variable parameters (2). A modulation occurs that involves a brain-stem circuit composed of opioid receptors/cannabinoid system, which is partially suppressed with anti-emetic treatments (3). Another emphasized concept is ‘the vomiting center’. Blockage of several types of vomiting by neurokinin 1 receptor antagonist drugs support the presence of such a pathway (4). The nucleus tractus solitarius (NTS) is located in lower brainstem and takes inputs from cerebral structures, vestibular system, area postrema, and intestinal structures, and forms the basis for vomiting (1,5). The clinical picture observed during pregnancy is named nausea-vomiting of pregnancy (NVP). In some patients, this process can get out of control and become a refractory condition known as ‘hyperemesis gravidarum (HG)’. Electrolyte imbalance, ketonuria, weight loss, and occasional need for hospitalization occur in addition to excessive gagging, nausea, and vomiting (6). HG is generally characterized by vomiting for more than 3 days, dehydration, severe dry mouth, decreased skin turgor, and loss of >5% of body weight (7).

NVP is very common and affects 70-80% of patients, whereas the prevalence of HG is 0.3-0.8% (8). The role of severe maternal HG on brain function of both the mother and fetus have not yet been clearly understood. General opinion states that fetal brain develops most prominently in the 3rd trimester and it is most interactive with mother’s brain at this stage (9). Significant progression occurs, especially in signal processing, coordination of complex functions, and basic vital functions (10,11). Dehydration, electrolyte imbalance, ketosis, hypokalemia, metabolic alkalosis, increased urea, impairment of liver enzymes and hemoconcentration due to plasma volume loss, and increased hematocrit are typical findings in HG (7,12). HG is known to show familial susceptibility, and associated with nulliparity, multiple pregnancies, and increased body weight; these factors also interact with growth hormones, gastric electrical activity, lipids, thyroid functions, diet and psychologic conditions (11,13). These events also affect the

central nervous system. The neurologic picture varies from loss of muscle strength accompanied by hyporeflexia, ophthalmoparesis, nystagmus, and papillary stasis to comatose state (14).

The aim of this study was to evaluate the effect of disease on the central and autonomic nervous systems by assessing spectral power analyses of electroencephalograph (EEG) signals from women with HG. We suggest a new approach that will help in the differential diagnosis of HG at the clinical level.


Study groups: This study included EEG signals of 30 normal pregnant women who were followed up in the Obstetrics and Gynecology Department of Selçuk University Faculty of Medicine between January 2013 and September 2014, and 33 patients who were diagnosed as having HG.

Results

Inclusion criteria: Patients aged between 18-40 years, 6-20 weeks of singleton pregnancy, admitted to neurology ward with symptoms of HG (HG criteria were severe nausea-vomiting, limitation of oral intake, weight loss, electrolyte imbalance, and moderate ketonuria), and with no neurologic, hepatic, or gastrointestinal comorbid disorders were selected. Approval from Selçuk University Ethics Committee was obtained and informed consent forms were signed by the patients.

Exclusion criteria were patients aged below 18 or above 40 years of age, twin or triple pregnancies, smoking during pregnancy, had history of an eating disorder/malnutrition, taking medications due to a neurologic, hepatic, or gastrointestinal disorder or refused to sign informed consent form were excluded. No significant difference was found in age distribution of the HG and the control groups (HG group; 27.21±4.67 years, control group; 24.87±6.11 years). Rate of multiparity and nulliparity slightly increased in the HG group with increasing age. There was no significant difference between pregnancy weeks of the groups (HG group; 11.26±4.17 weeks and control group; 9.89±5.08 weeks). Additionally, three patients in the HG group and two patients in the control group were left-handed. This difference was not statistically significant. Record of the EEG signals; EEG recordings were performed using a 40-channel Grass-TecCOMET device with the international 10-20 evaluation system. Channels for ECG and photic stimulation were removed, which yielded 36 channels for evaluation. Signals in the EEG laboratory were recorded digitally using The European

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yoğunluğu ile tüm alt bantlar delta, teta, alfa ve beta olmak üzere oluşturulmuş ardından güç spektral yoğunlukları hesaplanmıştır. Her bir frekans alt bantı güç yoğunluğu o kanaldaki 0,5-30 Hz arası toplam güç yoğunluğuna bölünerek ortalama değerler göreceli olarak elde edilmiştir.

Bulgular: Sonuç olarak ortalama güç yoğunluğu bakımından Fp1F3 için delta bandı, C3P3, F3C3, Fp1F3, P3O1, T5O1 için teta bantı anlamlı değişiklik gösterirken, diğer kanallar ve alt bantlarında anlamlı fark görülememiştir (p<0,05).

Sonuç: HG ve normal gebelerde EEG sinyalleri güç spektral yoğunluğu bakımından incelendiğinde sol hemisferin frontal alanında delta bandı, fronto sentro-parietal, parieto-oksipital alanlarda teta bantı anormalliği gözlenmiştir. Literatür ışığında bakıldığında HG’nin serebral aktivite anormalliği net gösterilemediği gibi yeri de tam belirlenememiştir. Ancak bu çalışmamızda olasılıkla ilk kez sol serebral hemisferin teta-delta bant aktivite anormalliği ve lokalizasyon farklılıkları gösterilmiştir. Bu nedenle rutin EEG çekimlerine spektral güç analizi yapılarak HG olguların ayırıcı tanısında yardımcı olabilecek bir lokalizasyon tespit edilmiştir.

Anahtar Kelimeler: Hiperemezis gravidarum, gebelik, elektroensefalografi, spektral güç yoğunluğu

Turk J Neurol 2016;22:73-79Ekmekçi et. al.; Cerebral Localization in Hyperemesis Gravidarum

Data Format (*.edt), which is a preferable format for storage of multichannel biologic and physical signals, and analyses were made by an experienced engineer using the MATrix LABoratory program. EEG signals are typically divided into 4 frequency domains, namely alpha, beta, delta, and theta (15,16,17). Basic EEG frequency subdomains and their frequencies are given in Table 1. Spectral analysis methods: This study used spectral analysis methods that evaluate periodic and nonperiodic signals in a frequency spectrum. Frequency information hidden in the time axis can be revealed and frequency-power changes can be assessed graphically with this method. The power spectrum of the signals is the square power of frequency amplitudes. The power component shows the ability of that signal to function in the given frequency. The Welch method, which is a nonparametric method of power spectrum analysis, was used in this study. The Welch method calculates periodograms by dividing signal into overlapping windows and then deriving

mean values of these periodograms (18). With regards to the sampling frequency of the EEG device used in this study, frequency resolution was set at 0.1 Hz intervals. Among the parameters of the Welch method, the overlapping rate was 0.5, windowing method was Hamming windows, and the window frequency was 128 Hz. Every channel of each patient was analyzed one-by-one using the Welch method and frequency power spectrums were obtained. Figure 1a gives the full extent of EEG signals in Fp1-F7 and F7-T3 channels of a healthy subject and Figures 1b and 1c show the power-frequency spectra of the given channels calculated using the Welch method.

All power spectral densities of sub-domains from every channel of each patient were summed at 0.5-4 Hz delta, 4-8 Hz theta, 8-13 Hz alpha, and 13-30 Hz beta. For every channel, the total power between 0.5-30 Hz was calculated and then divided to the sum of the powers of all sub domains. In this way, the relative sub-band values were calculated. In order to make patient-control comparisons of sub-band data, lists that comprised delta, theta, alpha, and beta were produced. Statistical analyses were performed for same channel and sub frequencies in all patients and the presence of a significant difference according to power density of frequencies was assessed. Hypothesis testing methods for 2 groups were used because there were two independent groups. The Kolmogorov normal distribution test was used to determine whether subfrequency domains complied with subfrequency bands. In the Kolmogorov test, results with a p<0.05 value are not consistent with normal distribution but results with a p value >0.05 are consistent with normal distribution. The t-test was used for bands that were normally distributed and Mann-whitney u test

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Figure 1a. Condensed electroencephalograph signals for Fp1-F7 and F7-T3 channels

Figure 1b. Frequency-power spectrum for Fp1-F7 channel Figure 1c. Frequency-power spectrum for F7-T3 channel (Welch method)

Table 1. Electroencephalograph sub-band and frequency interval

EEG sub-bands

Frequency interval (Hz) (c/sec)

Delta 0.5-4 (Delta 1; 0.10-1.48 and Delta 2; 1.56-3.51)

Theta 4-8 (Theta 1; 3.61-5.57 and Theta 2; 5.66-7.52)

Alpha 8-13 (Alpha 1; 7.62-9.47 and Alpha 2; 9.57-12.50)

Beta 13-30 (Beta 1; 12.60-17.48 and Beta 2; 17.58-30.0)EEG: Electroencephalograph


was used for bands that were not normally distributed. Table 2

shows the results of the Kolmogorov normal distribution test. In

this table, channel and band results that did not distribute normally

are shown in red. In statistical evaluations, p<0.05 was accepted as

statistically significant.

Results

Thirty-three patients with HG were compared with 30 age and sex-matched healthy controls. The nonparametric Welch method was used for power spectrum analysis. Data was obtained for wave frequencies of all cerebral bioelectrical activities. These data included all EEG electrode recording areas of the brain. All waves were classified according to detailed subfrequency groups. Obtained data were statistically compared according to spectral power analysis data (Table 2). Results of appropriate tests and p values for parameters with normal and non-normal distribution are given in Table 3. Analyses were performed to evaluate whether the mean difference in relative power changes in delta, theta, alpha, or beta sub-bands of the controls and the patients were statistically significant. According to p values in Table 3, there were significant differences in Fp1F3 sub-band in delta and C3P3, F3C3, Fp1F3, P3O1, T5O1 sub-bands in theta channels but there were no significant changes in other channels or sub-bands (p<0.05). The mean increase and decrease data for sub-bands that had significant changes are given in Table 4.

According to the results of spectral power analyses, places of cerebral activity (hemispheres and electrode recording areas) that show differences are shown schematically: theta band channels that had significant differences (Figure 2a) and delta band channels that had significant differences are colored in Figure 2b.

Discussion

Basis of this study was the content of EEG, which is among the best methods to show central nervous system function during the HG period. However, although EEG evaluation sometimes gives very important findings, it is also very variable. EEG is far from being a diagnostic method in HG, which is not clearly understood and includes multiple factors. Therefore, there are very few studies in the literature and most of them did not use direct methods. Many studies exist in the literature that analyzed EEG in patients with HG. Vaknin et al. (15) used EEG to investigate changes in

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Figure 2a. Channels with significant changes in theta band Figure 2b. Channels with significant changes in delta band

Table 2. Results of distribution for spectral power analysis of electroencephalograph tracings of hyperemesis gravidarum and healthy patients

Delta Theta Alpha BetaC3P3 0.349 0.253 0.013* 0.004

C4P4 0.500 0.286 0.114 0.006

CZPZ 0.396 0.996 0.109 0.013

F3C3 0.768 0.824 0.189 0.085

F4C4 0.914 0.597 0.113 0.017

F7T3 0.534 0.728 0.066 0.119

F8T4 0.960 0.930 0.370 0.002*

FZCZ 0.589 0.870 0.095 0.008

Fp1F3 0.192 0.993 0.008 0.002*

Fp1F7 0.059 0.617 0.004 0.001*

Fp2F4 0.396 0.685 0.043 0.001*

Fp2F8 0.122 0.622 0.125 0.005

P3O1 0.652 0.596 0.171 0.009

P4O2 0.176 0.302 0.253 0.005

T3T5 0.586 0.498 0.095 0.223

T4T6 0.153 0.879 0.219 0.031

T5O1 0.326 0.811 0.489 0.037

T6O2 0.272 0.253 0.390 0.012Kolmogorov normal distribution test values, *p>0.05


electrical activity of the central nervous system that occurred in patients with HG in the first 3 months of pregnancy. The authors investigated 17 patients with HG and 18 normal pregnant women; EEG abnormalities were observed in five of 17 patients with HG but none of the controls. Study results showed that patients with HG revealed more pronounced EEG findings than normal pregnant women who had no nausea or vomiting. Many physiologic factors affect EEG evaluations. For example, structured functions like verbal fluency, or weird thought content in women cause more significant cerebral inter-hemispheric asymmetry compared with men (19). Another important difference is the EEG changes during the menstrual period, a decrease in alpha rhythm and increase in theta band power are seen in the follicular phase. During the ovulatory period there is a striking difference in the frontal leads (20). In normal pregnancy, evaluation of EEG spectral analysis changes demonstrated significant changes between trimesters and in the postpartum period. However, hypertension during pregnancy and its effects on EEG activity have been widely investigated (21).

EEG signals are non-periodic signals that have a structural amplitude of 1-100μV and a frequency of 0.5-100 Hz (16,22). Although they have a wide frequency band, the range between 0.5-30 Hz has clinical and physiologic significance. Changes in amplitude and frequency are irregular signals that vary according to disease status. It is not logical to ask which signal appears at which time interval because frequency components occur at every

moment in periodic signals. In non-periodic signals such as EEG, not every frequency component appears in every time period and some frequency components appear and disappear at certain intervals (23). Therefore, it is not possible to observe incident frequency components from time domain signals of routine EEG traces. These data hidden in the time domain may be mapped and frequency components may be observed in the time axis using Fourier transformation. Therefore, we aimed to mathematically analyze EEG data using sub-bands and spectral power analysis, which is explained in detail in the method section. In this way, our target was to determine which brain areas were involved at which rate in these patient groups. Fourier transformation is a mathematical method that divides these signals into cosinus and sinus components, and graphically maps frequency amplitude data; it is a common signal processing technique used for analysis of biomedical signals such as EEG, ECG, and EMG (24). With spectral analysis of routine EEG tracings, level of consciousness and conditions/diseases such as brain trauma (25), epilepsy (26), Alzheimer’s disease (27), schizophrenia (28), and sleep disturbances (29) can be analyzed. Spectral analyses are divided as parametric and non-parametric analysis methods. These methods are commonly used signal processing techniques to analyze biomedical signals and for artificial intelligence. The most important finding of our study was the increased mean theta band power, as shown in Table 4. The mean power was lower in a delta band, which showed significance. The analyses showed that the mean strength of theta bands of C3P3, F3C3, Fp1F3, P3O1, and T5O1 channels and the delta band of the Fp1F3 channel were significantly different in patients with HG compared with controls. A significant increase in strength was observed, especially in the theta band in the frontocentral, centro-parietal, parieto-occipital, and temporo-occipital regions of the left hemisphere. In addition, a decrease in strength of delta band was observed in the whole brain, particularly in the frontal leads of the left hemisphere. The exact pathogenesis of HG is unknown (30).

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Table 4. Cerebral distribution of spectral power analysis differences in electroencephalograph recordings of hyperemesis gravidarum and healthy pregnant women (*Increase or decrease in sub-band cerebral bioelectrical activity relative to healthy brain activity)

Place of the lead of cerebral record

Band interval (1 and 2 subtypes together)

Control group (n=30)

HG group (n=33)

Power(↑↓)*

C3P3 Theta 0.161598 0.202522 ↑

F3C3 Theta 0.156406 0.201330 ↑

Fp1F3 Theta 0.130940 0.171289 ↑

Fp1F3 Delta 0.765451 0.695848 ↓

P3O1 Theta 0.146482 0.190351 ↑

T5O1 Theta 0.138204 0.183205 ↑HG: Hyperemesis gravidarum

Table 3. Comparison of spectral power analysis data of the electroencephalograph recordings of hyperemesis gravidarum and healthy pregnant women

Delta Theta Alpha Beta

C3P3 0.709 0.045 * 0.794 0.409

C4P4 0.638 0.509 0.442 0.630

CZPZ 0.925 0.105 0.522 0.417

F3C3 0.239 0.010* 0.868 0.525

F4C4 0.805 0.458 0.806 0.945

F7T3 0.915 0.149 0.534 0.561

F8T4 0.777 0.780 0.931 0.371

FZCZ 0.346 0.960 0.156 0.601

Fp1F3 0.044* 0.008* 0.104 0.093

Fp1F7 0.269 0.102 0.554 0.563

Fp2F4 0.368 0.748 0.386 0.371

Fp2F8 0.124 0.309 0.189 0.205

P3O1 0.696 0.015* 0.259 0.826

P4O2 0.566 0.191 0.981 0.329

T3T5 0.759 0.069 0.378 0.958

T4T6 0.857 0.249 0.804 0.582

T5O1 0.757 0.032 0.571 0.483

T6O2 0.766 0.480 0.891 0.880

*p>0.05


The most commonly accepted approach is the presence of metabolic and endocrinologic changes stemming from the placenta. NVP occurs when human chorionic gonadotropin level is elevated and human chorionic gonadotropin (hCG) is elevated when NVP is most significant (21). Other proposed factors for HG include the effect of Helicobacter pylori, gastrointestinal dysmotility, and psychogenic factors (1,5,6,30). An important point in gastric and intestinal passage is the dysfunction of enteric nervous system (10,17). HG appears clinically when there is a significant disturbance in sympathetic adrenergic and cholinergic function (10). Vagal innervation is important in homeostasis, satiety, nausea, and sphincter tonus (31). Vagal motor stimulation stimulates both cortical pathways and enteric stretch receptors via nucleus ambiguous (31,32). In this way, it forms the basic mechanism of intestinal movements, gagging, and vomiting. This functions at a microneural level and may play a role in neuromodulation of the primary symptoms of HG (10). The most important complication of HG is electrolyte deficiency and acute thiamine deficiency due to nutritional impairment. This condition is very rare and may lead to Wernicke encephalopathy. Korsakoff syndrome develops after WE (13). At such severe conditions, acute lesions are most prevalent in the periaqueductal and periventricular gray matter, mammillary body, and anterior and medial thalamus. Generalized cortical and subcortical involvement, and multiple cranial nerve involvement may occur and dentate nucleus, caudate nucleus, nucleus ruber, and splenium of corpus callosum may be affected (13). Central pontine myelinolysis is another clinical picture (13). Locations in the brain that are affected in advanced periods of HG reflect that gastrointestinal autonomic involvement may be important in the pathogenesis of HG and it may affect the cerebral factor. The following mechanism can be proposed to explain left hemispheric localization of cerebral bioelectrical activity in HG and significant impairment in spectral power distribution of delta and theta bands found in our study.

The first triggering factor in HG development is placental hCG; NTS is stimulated at the brainstem level over vagal and sympathetic adrenergic pathways (1). Discharges from there affect the hypothalamus, amygdala, limbic pathways, other periventricular gray matter areas, subcortical nuclei, and splenium (13). Enteric stimulation that originates from the vagus probably causes neuromodulation in the dominant hemisphere of the brain at our determined regions, especially at slow frequency theta and delta sub-band frequencies.

Using spectral power density, we showed that related localizations of dominant left hemisphere are changed in patients with HG when compared with pregnancies with normal courses. Frontal regions were predominant and central and middle parietal-occipital regions revealed different spectral power; these were the most important findings of our study. The importance of left hemisphere lateralization is the changes in theta and delta band intervals. There was an increase in theta band spectral analysis in tissues next to the left midline. Future research is required using both electrophysiologic methods and complementary methods such as functional MRI to explain both the mechanism of delta spectral power change and their relation with the disease.

Study LimitationsThe most important limitations of this study were the small

sample size and low specificity of the methods. However, the role of the brain in HG should be confirmed with functional imaging methods to confirm this important topic.

Ethics

Ethics Committee Approval: The study was approved by the Selçuk University of Local Ethics Committee.

Informed Consent: Consent forms were filled out by all participants.Peer-review: External and internal peer-reviewed.


Concept: Hakan Ahmet Ekmekçi, Design: Hakan Ahmet Ekmekçi, Data Collection or Processing: Hakan Ahmet Ekmekçi, Arzu Setenay Yılmaz, Analysis or Interpretation: Hakan Ahmet Ekmekçi, Muhammet Üsame Öziç, Yüksel Özbay, Literature Search: Hakan Ahmet Ekmekçi, Writing: Hakan Ahmet Ekmekçi.



References1. Horn CC. Why is the neurobiology of nausea and vomiting so important?

Appetite 2008;50:430-434.2. Stockhorst U, Steingruebe rHJ, Enck P, Klosterhalfen S. Pavlovian

conditioning of nausea and vomiting. Autonomic Neuroscience: Basic and Clinical 2006;129:50-57.

3. Parker LA, Limebeer CL, Kwaitkowska, M. Cannabinoids: effects on vomiting and nausea in animal models. In: Mechoulam, R. editor. Cannabinoids as Therapeutics. Switzerland: Birkhauser Verlag/Switzerland; 2005. p. 183-200.

4. Miraglia L, Pagliarusco S, Bordini E, Martinucci S, Pellegatti M. Metabolic disposition of casopitant, a potent neurokinin-1 receptor antagonist in mice, rats, and dogs. Drug Metab Dispos 2010;38:1876-1891.

5. Sanu O, Lamont RF. Hyperemesis gravidarum: pathogenesis and the use of antiemetic agents. Expert Opn Pharmacother 2011;12:737-748.

6. Goodwin TM. Hyperemesis gravidarum. Obstet Gynecol Clin N Am 2008:35;401-407.

7. Köşger H, İkbal K. Hiperemezis Gravidarum’a güncel yaklaşımlar. Yeni Tıp Dergisi 2014;31:159-162.

8. Askling J, Erlandsson G, Kaijser M, Akre O, Ekbom A. Sickness in pregnancy and sex of child. Lancet 1999;354:2053.

9. Keunen RWM, Vliegen JHR, van der Pol DAE, Gerretsen G, Stam CJ. The electroencephalogram during normal third trimester pregnancy and six months postpartum. Bri J of Obstet Gynaecol 1997;104:256-258.

10. Walia R, Aggarwal A, Wadhwa Y. Investigating EEG Characteristics of a Pregnant Women. International Journal of Emergency Medicine 2013;2:14-19.

11. Hughes JD, Nayak NG, Aslam N, Rashed H, Cardoso S, Familoni B, Karas JG, Shaver C, Egerman RS, Wallstedt A, Riely CA, Abell LT. Autonomic and Enteric Nervous System Dysfunction May Play a Role in Hyperemesis Gravidarum. Gastroenterol Res 2015;8:153-156.

12. Goodwin TM. Hyperemesis gravidarum. Clin Obstet Gynecol 1998;41:597-605.

13. Abell TL, Riely CA. Hyperemesis gravidarum. Gastroenterol Clin North Am 1992;21:835-849.

14. Zara G, Codemo V, Palmieri A, Schiff S, Cagnin A, Citton V, Manara R. Neurological complications in hyperemesis gravidarum. Neurol Sci 2012;33:133-135.

15. Vaknin Z, Halperin R, Schneider D, Teitler J, Dar P, Herman A, Berkovitch M. Hyperemesis gravidarum and nonspecific abnormal EEG findings: a preliminary report. The Journal of Reproductive Medicine 2006;51:623-627.

78


16. Teplan M. Fundamentals of EEG measurement. Measurement Science Review 2002;2:1-11.

17. West M, Parkinson D, Havlicek V. Spectral analysis of electroencephalographic response to experimental concussion in the rat. EEG and Clin Neurophysiol 1982;53:192-200.

18. Tokmakci M, Asyali MH, Seğmen, H. Examining EEG signals with parametric and non-parametric analyses methods in migraine patients during pregnancy. In: Biomedical Engineering Meeting. 15th ed. (BIYOMUT), 2010:1-4.

19. Razumnikova OM. Gender differences in hemispheric organization during divergent thinking; an EEG investigation in human subjects. Neurosci Lett 2004;362:193-195.

20. Vasil’eva VV. Spectral and coherent characteristics of EEG in women during various phases of menstrual cycle. Bull ExpBiol Med 2005;140:383-384.

21. Brussé IA, Peters NCJ, Steegers EAP, Duvekot JJ; Visser GH. Electroencephalography during Normotensive and Hypertensive Pregnancy: A systemic Review. Obs and Gyn Survey 2011;65:794-803.

22. Rao SVM, Koya JR, MandadiNK, Mitta SK. Electroencephalographic signals for recognizing speaking effort–brain computer ınterface 2013;8:62-67.

23. Adeli H, Zhou Z, Dadmehr N. Analysis of EEG records in an epileptic patient using wavelet transform. Journal of Neuroscience Methods 2003;123:69-87.

24. John LS. Biosignal and Biomedical Image Processing. In Marcel Dekker, MATLAB based Applications. NY, 2004:271-301.

25. Goldfine AM, Victor JD, Conte MM, Bardin JC, Schiff ND. Determination of awareness in patients with severe brain injury using EEG power spectral analysis. Clinical Neurophysiology 2011;122:2157-2168.

26. Direito B, Teixeira C, Ribeiro B, Castelo-Branco M, Sales F, Dourado A. Modeling epileptic brain states using EEG spectral analysis and topographic mapping. Journal of Neuroscience Methods 2012;210:220-229.

27. McBride JC, Zhao X, Munro NB, Smith CD, Jicha GA, Hively L, Jiang Y. Spectral and complexity analysis of scalp EEG characteristics for mild cognitive impairment and early Alzheimer's disease. Computer Methods and Programs in Biomedicine 2014;114:153-163.

28. John JP, Rangaswamy M, Thennarasu K, Khanna S, Nagaraj RB, Mukundan CR, Pradhan N. EEG power spectra differentiate positive and negative subgroups in neuroleptic-naive schizophrenia patients. J Neuropsychiatry Clin Neurosci 2009;21:160-172.

29. Lundahl J, Deacon S, Maurice D, Staner L. EEG spectral power density profiles during NREM sleep for gaboxadol and zolpidem in patients with primary insomnia. Journal of Psychopharmacology 2012;26:1081-1087.

30. Lee NM, Saha S. Nausea and Vomiting of Pregnancy. Gastroenterol Clin North Am 2011;40:309-334.

31. Ratcliffe EM, Farrar NR, Fox EA. Development of the vagal innervation of the gut: steering the wandering nerve. Neurogastroenterol Motil 2011;23:898-911.

32. Phillips RJ, Powley TL. Tension and stretch receptors in gastrointestinal smooth muscle: reevaluating vagal mechanoreceptor electrophysiology. Brain Research 2000;34:1-26.

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Case Report / Olgu SunumuDO I:10.4274/tnd.39205Turk J Neurol 2016;22:80-83

Hemichorea and Hemiballismus Associated with Cerebral Vascular Malformation Induced by Hyperglycemia: Case Report

Hipergliseminin Tetiklediği Serebral Vasküler Malformasyona Bağlı Hemiballizm ve Hemikore: Olgu Sunumu

Ferda Selçuk1, Mine Hayriye Sorgun2, Süha Akpınar3

1Dr. Burhan Nalbantoğlu State Hospital, Clinic of Neurology, Nicosia, Turkish Republic of Northern Cyprus2Ankara University Faculty of Medicine, İbni Sina Hospital, Clinic of Neurology, Ankara, Turkey

3Near East State University Hospital, Clinic of Radiology, Nicosia, Turkish Republic of Northern Cyprus

80

Ad dress for Cor res pon den ce/Ya z›fl ma Ad re si: Mine Hayriye Sorgun MD, Ankara University Faculty of Medicine, İbni Sina Hospital, Clinic of Neurology, Ankara, Turkey Phone: +90 543 890 09 34 E-mail: [email protected]


Hemichorea, hemiballismus, and hyperglycemia associated with vascular malformation is rare. We report a patient who presented with involuntary movements in the left-side with concurrent hyperglycemia. The patient had type 2 diabetes mellitus (DM) and a venous angioma in the basal ganglia on the cranial magnetic resonance imaging (MRI). A woman aged 49 years presented with flinging and throwing movements of the left upper and lower limb, which she had had for one month. Her neurologic examination confirmed involuntary, irregular, wide amplitude movements of the left limbs consistent with left hemiballismus. She had hypertension and type 2 DM. Her glucose level was 400 mg/dL. Cranial MRI showed a cavernoma in the right subependymal area of the lateral ventricle and a venous angioma in the right nucleus lentiformis, which was confirmed on digital subtraction angiography. Hemiballismus improved after blood glucose level had been regulated in the follow-up period. Especially in the elderly secondary causes should be investigated in patients with acute or subacute onset of chorea-ballismus. We think that our patient’s clinical presentation was induced by unregulated DM. Venous angioma with chorea-ballismus is rarely stated in literature and we presume the mass effect of venous angioma could be responsible of our clinical findings.

Keywords: Chorea, ballismus, vascular malformation, hyperglycemia

Vasküler malformasyona bağlı hemiballizm, hemikore ve hiperglisemi birlikteliği olgusuna az rastlanmaktadır. Biz burada başlangıç kliniği sol taraflı istemsiz hareketler olan, yapılan tetkiklerde hiperglisemi saptanan, iyi regüle edilememiş tip 2 diabetes mellitus (DM) özgeçmişi olan ve kranyal manyetik rezonans görüntülemede (MRG) bazal ganglionlar düzeyinde venöz anjiom tespit edilen bir olguyu sunuyoruz. Kırk dokuz yaşındaki kadın hasta, yaklaşık bir aydır sol kol ve sol bacakta, istemsiz, atma şeklindeki hareket şikayeti ile başvurdu. Özgeçmişinde hipertansiyon ve tip 2 DM öyküsü vardı. Hastanın muayenesinde sol taraflı, kalça ve omuzdan başlayan, şiddetli, atma şeklinde hemiballizm görüldü. Hastanın bakılan tetkiklerinde kan şekeri 400 mg/dL olarak ölçüldü. Kranyal MRG’sinde sağ nükleus lentiformis düzeyinde venöz anjiyom ve sağ lateral ventrikül korpus lateralinde, subependimal yerleşimli, vasküler malformasyonu düşündüren lezyon tespit edildi ve ardından dijital dört damar serebral anjiyografisinde gösterildi. Takibinde kan şekeri regülasyonu sağlanan hastanın hemiballizminde tama yakın klinik düzelme oldu. Özellikle ileri yaşlı olgularda, akut veya subakut başlangıçlı kore-ballizm, özellikle sekonder nedenleri akla getirmelidir. Vasküler malformasyona bağlı hemiballizm, hemikore ve hiperglisemi birlikteliği olgusuna az rastlanmaktadır. Sunulan olguda iyi regüle edilememiş DM hastamızın kliniğinin belirmesinde kolaylaştırıcı etken olduğunu ve yine literatürde az rastlanan venöz anjiyom ve kore-ballizm birlikteliğinde, venöz anomalinin özellikle kitle etkisinin klinikten sorumlu olabileceğini düşünüyoruz.

Anahtar Kelimeler: Kore, ballizm, vasküler malformasyon, hiperglisemi

Sum mary

Öz

Turk J Neurol 2016;22:80-83Selçuk et. al.; Hemichorea and Hemiballism Associated with Cerebral Vascular Malformation Induced by Hyperglycemia

Introduction

The term chorea, which is included in hyperkinetic disorders, means ‘dance’ in Greek and is used for irregular muscle contractions that are clinically random, arrhythmic, short-lived, low amplitude, sudden and jerky in nature, and involving distal parts of extremities especially, and sometimes the tongue (1). If severity and amplitude of these involuntary movements increase and involve proximal parts of extremities they are called ballismus (1). Chorea and ballismus may sometimes co-occur or follow each other (2). If they involve only one half of the body they are called as hemichorea or hemiballismus (1). Hemiballismus may sometimes occur together with other involuntary movements such as dystonia, myoclonus, or orofacial tics (2). These movements rarely occur intermittently; they are usually continuous in nature and can be interrupted by patients only for short periods of time (1). Their disappearance during sleep is characteristic. Putamen and globus pallidus are important for choreic and ballistic movements and subthalamic nucleus pathologies are especially important for ballismus (2). They can be classified as primary (neurodegenerative diseases) or secondary (autoimmune, structural, vascular, metabolic, and iatrogenic) according to the etiology (2). Late-onset cases are secondary and vascular causes are usually prominent (2,3,5,6,7,8,9,10,11,12,13,14). Infarct, hemorrhage, cavernoma, and arteriovenous malformation (AVM) are among the possible vascular causes (2,3,5,6,7,8,9,10,11,12,13,14). Metabolic disturbances including hyperglycemia, particularly non-ketotic hyperglycemia may be associated with many neurologic disorders (4). Chorea-ballismus is among the most common of these neurologic disorders (4). Co-occurrence of hemiballismus, hemichorea, and hyperglycemia due to vascular malformation is rarely seen (5,15,16). We present a woman who presented with left-sided involuntary movements. Hyperglycemia was detected in a blood analysis and she had a history of type 2 diabetes mellitus (DM). A venous angioma was detected at the level of the basal ganglia in cranial magnetic resonance imaging (MRI).

Case Report

A woman aged 49 years presented with involuntary jerks in her left arm and leg, which she had had for nearly a month. She had never been admitted to a center for these symptoms before. Her medical history was not significant except for hypertension and type 2 DM. The patient’s type 2 DM was diagnosed 5 years earlier but she did not use her diabetes drugs and had not adhered to her diet for the last 6 months. With the exception of the left-sided severe hemiballismus, which started from the hip and shoulder, her physical and neurologic examinations were normal. Her laboratory analysis revealed a blood glucose of 400 mg/dL. Cranial MRI showed a 10x13-mm cavernoma located subependymally on the lateral side of the ventricular corpus in the right hemisphere, which had heterogeneous signal intensity. Its periphery was hypointense, especially in T2-weighted and FLAIR sequences, and susceptibility-weighted imaging (SWI) suggested a vascular lesion (Figures 1, 2, 3). Digital 4-vessel cerebral angiography evaluation revealed findings consistent with venous angioma at the level of the left nucleus lentiformis. The patient’s blood sugar was regulated in approximately 1 month. Haloperidol was stopped after 3 weeks

because of a high level of somnolence. At the end of the month, near-total improvement was seen in choreiform movements. She had no active symptoms during her 2 years of follow-up. Then her left-sided choreiform movements restarted and analysis again revealed hyperglycemia. Her HgbA1c value was 11.2%. Repeated cranial MRI revealed no significant change.

Discussion

Secondary causes should be kept in mind in acute or subacute onset chorea-ballismus in patients at advanced ages (2). These causes include drugs, vascular diseases, metabolic causes, autoimmune diseases, neoplasia, senility, and hereditary causes

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Figure 1. A hypointense lesion at the level of basal ganglia in right hemisphere consistent with vascular malformation; magnetic resonance susceptibility-weighted image

Figure 2. A subependymal cavernoma in the right hemisphere, T2-weighted magnetic resonance imaging, axial section

Turk J Neurol 2016;22:80-83 Selçuk et. al.; Hemichorea and Hemiballism Associated with Cerebral Vascular Malformation Induced by Hyperglycemia

(2,3,5,6,7,8,9,10,11,12,13,14). Hemichorea/hemiballismus is used to state presentation in on half of the body. They form approximately 0.7% of all movement disorders. They are usually associated with contralateral structural pathologies such as vascular lesions, tumors or tuberculomas, sometimes they may be associated with diabetic ketoacidosis, or non-ketotic hyperglycemia (5). Vascular etiologies that may cause chorea and ballismus include ischemic or hemorrhagic cerebrovascular events and vascular malformations (1,2,3,5,6,7,8,9,10,11,12,13,14). Vascular malformations consist of venous angiomas, AVM, and cavernous angiomas (6). Chorea due to vascular anomalies such as cerebral angioma, or cavernoma is rarely seen (7). The etiopathogenesis of chorea was tried to be explained by the disruption of balance between direct and indirect pathways. The impairment of striatal outputs that project to the globus pallidus externa (indirect pathway) increases inhibition of neurons at this region, and this decreases output of the globus pallidus externa by increasing inhibition on the globus pallidus interna. As a result, thalamocortical activity which is known to be the basic mechanism in hyperkinetic disorders develops. In the presented case, a venous angioma was detected at the level of the right nucleus lentiformis. Previous cases of chorea and ballismus associated with cavernoma have been reported (8,9,10,11,12,13,14). Very rarely cases have been associated with developmental venous anomalies (15,16). In these cases, venous hypo-perfusion associated with venous anomalies at the contralateral putamen level were detected. In the present case, possible hemodynamic changes due to the venous anomaly or a direct effect of the mass were thought to be responsible for the patient’s clinical situation.

The second most common cause of hemiballismus after stroke is hyperglycemia (17,18). Hyperglycemia associated with ballismus/chorea (HABC) is commonly seen in patients with DM aged between 50-80 years, whose blood glucose levels cannot be regulated (19,20). Typically, the clinical picture settles within

hours. During this period the patients’ blood glucose levels are between 400-1000 mg/dL and involuntary movements regress after control of hyperglycemia. Some patients have normal computed brain tomography (CBT) findings although others may have hyper-dense lesions in the basal ganglia. Cranial MRI evaluations may also be normal or they may demonstrate hyper-intense lesions in the putamen or caudate nucleus in T1-weighted images and variable intensity lesions in T2-weighted images (21,22,23). The pathophysiology of HABC has not yet been completely understood. Hyperglycemia may lead to tissue edema and this may increase vascular resistance and viscosity, decrease metabolic rate of neurons, inactivate Krebs cycle, and lead to consumption of gamma-aminobutyric acid (GABA) by the brain to produce energy (24). Moreover, Chang et al. (21) evaluated cranial MRI and MR spectroscopy findings of 18 patients with HABC and suggested that transient ischemia triggered by hyperglycemia may be responsible for the clinical picture. Shan et al. (24) suggested that ischemia triggered by hyperglycemia damages GABAergic neurons in particular, this affects the indirect pathway more prominently and thereby inhibits inhibition on the subthalamic nucleus. Additionally, hyperosmolarity decreases the epileptic threshold in the direct pathway, which increases firing of this pathway. At the end of all these processes, reactive swollen astrocytes and gliosis occur and these may cause petechial hemorrhages. This explains the hyper-density in acute CBT. We observed no such finding in the CBT of our patient. Oh et al. (22) performed a meta-analysis of 53 cases of HABC and demonstrated hyperintense lesions at the level of the putamen in T1-weighted images in all cases. Enhancement was also seen in T2-weighted images. Additionally, in our case a hypointense lesion in T2-weighted image was detected to be a venous anomaly. In the same study by Oh et al. (22) in 19 of 22 patients evaluated with MRI, cranial MRI findings disappeared with improvement in chorea; blood sugar regulation was sufficient in most patients and drug treatment was given very rarely. However, in the present case diabetes regulation was combined with haloperidol.

Conclusion

In conclusion, although the present case did not fully meet the HABC criteria, especially with imaging findings, we believe that poorly-regulated DM precipitated the clinical picture and regulation of diabetes formed the basis of our treatment. Moreover, we suggest that the mass effect and hypo-perfusion due to venous anomaly may be responsible for the clinical picture in rare cases of comorbid venous angioma and chorea-ballismus.

Ethics

Informed Consent: Consent form was filled out by this patient.Peer-review: Internal peer-reviewed.


Surgical and Medical Practices: Ferda Selçuk, Süha Akpınar, Concept: Ferda Selçuk, Mine Hayriye Sorgun, Design: Ferda Selçuk, Mine Hayriye Sorgun, Data Collection or Processing: Ferda Selçuk, Mine Hayriye Sorgun, Süha Akpınar, Analysis or Interpretation: Ferda Selçuk,

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Figure 3. Image of a cavernoma in the right hemisphere and a venous malformation at its anterior, magnetic resonance, susceptibility-weighted imaging-weighted image, axial section

Turk J Neurol 2016;22:80-83Selçuk et. al.; Hemichorea and Hemiballism Associated with Cerebral Vascular Malformation Induced by Hyperglycemia

Mine Hayriye Sorgun, Süha Akpınar, Literature Search: Ferda Selçuk, Mine Hayriye Sorgun,

Writing: Ferda Selçuk, Mine Hayriye Sorgun.Conflict of Interest: No conflict of interest was declared by the authors.Financial Disclosure: The authors declared that this study has received


References1. Cardoso F, Seppi K, Mair KJ, Wenning GK, Poewe W. Seminar on choreas.

Lancet Neurol 2006;5:589-602.2. Fahn S, Jankovic J. Principles and Practice of Movement Disorders.

Philadelphia: Churchill Livingstone/Elsevier, 2008. 3. Barut BÖ, Coşkun BE, Türksoy Ö. Choreiform movement disorder secondary

to ıntracerebral cavernoma: Case report. Turkish Journal of Neurology 2013;19:60-62.

4. Gürses C, Gökyiğit A. Metabolik ensefalopati. Öge AE, Baykan B Editörler, Nöroloji 2. Baskı içinde. Nobel Tıp Kitabevleri; 2011; s. 564-565.

5. Suchowersky O, Muthipeedika J. A case of late-onset chorea. Nat Clin Pract Neurol 2005;1:113-116.

6. Watts RL, Koller WC. Movement disorders neurologic principles and practice. Second edition. McGraw-Hill, 2004.

7. Bhidayasiri R, Truong DD. Chorea and related disorders. Post grad Med J 2004;80:527-534.

8. Dörner L, Buhl R, Hugo HH, Jansen O, Barth H, Mehdorn HM. Unusual locations for cavernous hemangiomas: report of two cases and review of the literature. Acta Neurochir (Wien) 2005;147:1091-1096.

9. Donmez B, Cakmur R, Uysal U, Men S. Putaminal cavernous angioma presenting with hemichorea. Mov Disord 2004;19:1379-1380.

10. Carella F, Caraceni T, Girotti F. Hemichorea due to a cavernous angioma of the caudate. Case report of an aged patient. Ital J NeurolSci 1992;13:783-785.

11. Carpay HA, Arts WF, Kloet A, Hoogland PH, Van Duinen SG. Hemichorea reversible after operation in a boy with cavernous angioma in the head of the caudate nucleus. J Neurol Neurosurg Psychiatry 1994;57:1547-1548.

12. López-Valdés E, Posada IJ, Muñoz A, Bermejo F. Acute hemichorea caused by a cavernous angioma in the caudate. Neurologia 1998;13:205-206.

13. Yakinci C, Durmaz Y, Korkut M, Aladag A, Onal C, Aydinli M. Cavernous hemangioma in a child presenting with hemichorea: response topimozide. J Child Neurol 2001;16:685-688.

14. Kobayashi K, Aoyama N, Sasaki J, Oshima H, Fukaya C, Yamamoto T, Katayama Y. MRI appearance of a cerebral cavernous malformation in the caudate nucleus before and after chorea onset. J Clin Neurosci 2011;18:719-721.

15. Kalia LV, Mozessohn L, Aviv RI, da Costa L, Lang AE, Shadowitz S, Masellis M. Hemichorea-hemiballism associated with hyperglycemia and a developmental venous anomaly. Neurology 2012;78:838-839.

16. Civardi C, Kalia LV, Collini A, Lang AE, Aviv RI, Masellis M. Hemichorea-hemiballism associated with hyperglycemia and a developmental venous anomaly. Neurology 2013;81;1181.

17. Postuma RB, Lang AE. Hemiballism: Revisiting a classic disorder. Lancet Neurol 2003;2:661-668.

18. Orhan EK, Atmaca MM, Atmaca M, Hanağası H. Chorea-Ballismus Associated with Hyperglycemia; case report. Nöropsikiyatri Arşivi 2013;50:375-378.

19. Lin JJ, Chang MK. Hemiballism-hemichorea and nonketotic hyperglycemia. J Neurol Neurosurg Psychiatry 1994;57:748-750.

20. Narayanan S. Hyperglycemia-induced Hemiballismus Hemichorea: A Case Report and Brief Review of the Literature. J Emerg Med 2010;19:1-3.

21. Chang KH, Tsou JC, Chen ST, Ro LS, Lyu RK, Chang HS, Hsu WC, Chen CM, Wu YR. Temporal features of magnetic resonance imaging and spectroscopy in non-ketotic hyperglycemic chorea-ballism patients. Eur J Neurol 2010;17:589-593.

22. Oh SH, Lee KY, Im JH, Lee MS. Chorea associated with non-ketotic hyperglycemia and hyperintensity basal ganglia lesion on T1-weighted brain MRI study: A meta-analysis of 53 cases including four present cases. J NeurolSci 2002;200:57-62.

23. Ahlskog JE, Nishino H, Evidente VG, Tulloch JW, Forbes GS, Caviness JN, Gwinn-Hardy KA. Persistent chorea triggered by hyperglycemic crisis in diabetics. Mov Disord 2001;16:890-898.

24. Shan DE, Ho DM, Chang C, Pan HC, Teng MM. Hemichorea-hemiballism: An explanation for MR signal changes. Am J Neuroradiol 1998;19:863-870.

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Case Report / Olgu SunumuDO I:10.4274/tnd.32650Turk J Neurol 2016;22:84-87

Progressive Myoclonic Epilepsy and NEU1 Mutation: A Different Phenotypic Case

Progresif Miyoklonik Epilepsi ve NEU1 Mutasyonu: Farklı Bir Fenotipik Olgu

Ebru Nur Vanlı Yavuz1, Güneş Altıokka1, Zeliha Matur1, Mikko Muona2, Nerses Bebek1, Candan Gürses1, Anna Elina Lehesjoki2, Ayşen Gökyiğit1, Betül Baykan1

1İstanbul University İstanbul Faculty of Medicine, Department of Neurology, Clinical Neurophysiology Unit, İstanbul, Turkey2University of Helsinki Faculty of Medicine, Institute for Molecular Medicine Finland, Helsinki, Finland

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Ad dress for Cor res pon den ce/Ya z›fl ma Ad re si: Ebru Nur Vanlı Yavuz MD, İstanbul University İstanbul Faculty of Medicine, Department of Neurology, Clinical Neurophysiology Unit, İstanbul, Turkey


Sialidosis are autosomal recessive inherited disorders caused by a mutation on the NEU1 gene. In type 1 sialidosis, a “cherry-red spot” can be observed in fundoscopic examinations. In this study, a woman aged 37 years without “cherry-red spot” on ophthalmologic examination is reported to draw attention to a new phenotypic variation. Although an ophthalmologic examination was normal, for patients with consanguineous parents with progressive ataxia, drug-resistant epilepsy and myoclonus must be investigated for progressive myoclonic epilepsy and genetic analysis for sialidosis must be performed. The diagnosis is also crucial for genetic consultancy of the family.

Keywords: Progressive myoclonic epilepsy, sialidosis, NEU1 gene mutation, cherry-red spot

Siyalidozlar, NEU1 geninde mutasyon sonucu gelişen otozomal resesif geçişli bir grup lizozomal depo hastalığıdır. Tip 1 siyalidozda tipik olarak fundus muayenesinde “cherry-red spot” görülür. Bu çalışmada “cherry-red spot” bulgusu olmadığı halde genetik incelemeler sonrasında NEU1 mutasyonu saptanan 37 yaşında kadın olgu, siyalidoz tablolarındaki fenotipik çeşitliliğe dikkat çekmek amacıyla sunulmuştur. Anne baba akrabalığı olan, ilerleyici ataksi, dirençli epilepsi ve miyoklonileri olan hastalarda progresif miyoklonik epilepsiler yönünden diğer etiyolojilerin yanı sıra fundus muayenesi normal olmasına rağmen siyalidoz da genetik açıdan araştırılmalıdır. Doğru tanı aileye danışmanlık verilmesi açısından önemlidir.

Anahtar Kelimeler: Progresif miyoklonik epilepsi, siyalidoz, NEU1 gen mutasyonu, cherry-red spot

Sum mary

Öz

Introduction

Sialidosis, which is among the rare causes of progressive myoclonic epilepsy (PME), involves a deficiency in the activity of lysosomal neuroaminidase 1 (NEU1) enzyme. It is an autosomal recessive lysosomal storage disease caused by a mutation in the NEU1 gene. It is divided into two groups depending on the onset of disease and clinical findings. Type 1 sialidosis has a relatively late onset. Its course is relatively benign, dysmorphic features are absent, ataxia, myoclonus, and seizures are present, and typically a “cherry-red spot” is seen in an examination of the fundus (1,2).

In type 2 disease with infantile onset, dysmorphic features, organomegaly, and severe mental retardation are seen. To date, 42 mutations that cause sialidosis have been reported on the NEU1 gene, which is located on the 6p21.6 locus of the 6th chromosome, and these mutations cause genetic heterogeneity (3,4).

We present a patient who had slowly progressive ataxia comorbid with refractory epilepsy and myoclonus. Her parents were 3rd degree relatives. Although she had been diagnosed as having PME for years, a true etiologic diagnosis could not be made due to the absence of a “cherry-red spot”; however, a genetic evaluation revealed NEU1 mutation. We present this case to

Turk J Neurol 2016;22:84-87Vanlı Yavuz et. al.; A Different Progressive Myoclonic Epilepsy: A Case Report

highlight the phenotypic variability in the clinical presentation of sialidoses.

Case Report

A woman aged 37 years from Siverek, Şanlıurfa, presented with symptoms of bilateral whole body tremor, jerks, and imbalance, which was prominent in the left hand, especially in the mornings. The symptoms first started when she was seventeen and generalized tonic-clonic seizures (GTCS) began in the same year. Her convulsions were triggered during periods of excitation and tremor also increased. Despite treatment with valproic acid, clonazepam, pyrimidone, and piracetam, the seizures repeated at least once a month. Speech disorder and forgetfulness joined these symptoms after 3-4 years. There was nothing significant in her medical history except two falls without loss of consciousness. Her family history revealed that her parents were 3rd degree relatives and her cousin, who was aged 6 years, a history of GTCS without accompanying tremor or jerks that started after a fall. Her neurologic examination revealed dysarthric speech, ataxia, and positive and negative myoclonus in extremities, which were generalized, synchronized, and augmented with action. She stood up with bilateral support, myoclonus increased when she stepped forward, and after a few steps she tended to fall due to negative myoclonus. Her mental status was within normal limits and she succeeded in university entrance exams. Anamnesis and physical examination findings suggested PME and etiologic assessments were performed. The differential diagnosis included Unverricht-Lundborg disease, Lafora disease, myoclonic epilepsy with ragged-red fibers, sialidosis, neuronal ceroid lipofuscinosis and celiac disease. A skin biopsy, which was evaluated twice, muscle biopsy, ophthalmic examination, duodenal biopsy, detailed biochemical analyses, and lactate value were normal and antigliadin antibodies were negative. Electroencephalograph (EEG) evaluation revealed mild and general disorder in organization, prominent in the anterior half of the hemispheres, and hypersynchronization in the vertex. Neuropsychologic evaluation revealed impairments in executive function (frontal signs) such as increase in interference time, deficiency in category formation and changing, perseverations and decrease in mental flexibility. Cranial magnetic resonance imaging (MRI) showed cerebral and cerebellar atrophy. Back-averaging was used for the neurophysiologic evaluation and approximately 20-ms discharges priming myocloni were observed in the contralateral brain hemisphere triggered by potentials recorded from superficial electrodes that were located on the left forearm extensor muscles. Median somatosensory-evoked potential (SEP) evaluation revealed bilateral giant cortical responses (>20 μV). With right median nerve stimulation, a moderate latency C reflex was recorded from the right thenar muscles. With double-stimulus transcranial magnetic stimulation no inhibitory response (which is expected under normal conditions) was seen after the 2nd stimulus at 100-ms interstimulus intervals. Nervous conduction, visual evoked potentials, and tibial SEP evaluations were within normal limits. The electrophysiologic findings of the patient are summarized in Figure 1. Although photosensitivity and typical generalized epileptiform activity were not observed, Unverricht-Lundborg disease was considered depending on the clinical features but genetic evaluations demonstrated a normal-sized cystathionine

B gene promoter region, and an increase in dodecamer repeat numbers or point mutations were not detected. SCARB2 gene was evaluated for autosomal recessive cerebellar ataxias because of the severe body ataxia and the result was negative. Laforin and Malin genes were evaluated despite absence of Lafora bodies in the skin biopsy, relatively mild course, and lack of prominent mental findings; no mutation was detected. Although the ophthalmologic evaluation was within normal limits, a NEU1 mutation leading to c.914G>A and c625delG protein variation was detected in the genetic evaluation, which was performed in Finland (5). A change in c625delG was previously defined in the same codon and was reported as pathogenic (6). However, the c.914G>A that we detected in the same codon has not been previously reported to be pathogenic (7). Repeated ophthalmologic evaluation confirmed absence of “cherry-red spot”. The patient, who had been followed up in our clinic for 14 years, was restricted to a wheelchair because of severe ataxia. GTCS declined in the last year after zonisamide 200 mg/day was added to her treatment, which previously comprised valproic acid 1500 mg/day, levetiracetam 2000 mg/day, and clonazepam 4 mg/day.

Discussion

PME is a rare group of genetic, symptomatic, and generalized epilepsies. Myoclonic seizures, GTCS, progressive neurologic findings, ataxia, and dementia are seen in patients with PME. The differential diagnosis is performed depending on age of onset, accompanying symptoms, cerebellar signs, and presence

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Figure 1. Electrophysiologic findings. Somatosensory-evoked potential responses obtained by stimulation of (a) right and (b) left median nerves at the wrist level. Giant cortical potentials (>20 μV); contralateral brain hemispheric discharges which prime myocloni for approximately 20 ms triggered by potentials recorded with superficial electrodes located over the left forearm using back averaging (c); C reflex recorded with approximately 55 ms latency from right thenar muscles after right median nerve stimulation (d)

Turk J Neurol 2016;22:84-87 Vanlı Yavuz et. al.; A Different Progressive Myoclonic Epilepsy: A Case Report

of dementia but a definite diagnosis is difficult due to variability of etiologies and phenotypes (8). Sialidoses are very rare diseases that are listed in PME etiologies, and diagnosis is usually made by genetic confirmation after observation of elevated urinary sialic acid or by demonstration of neuraminidase enzyme defect in fibroblast cultures (6,9). They are usually missed in patients with PME who lack typical clinical findings and “cherry-red spot”. Nevertheless, we detected a mutation in the NEU1 gene in our patient.

Myoclonus in these patients limits activities of daily life after progression of disease, and may cause injuries due to falls (8). Although hypothesis of gamma-aminobutyric acid dysfunction in inhibitory interneurons was proposed, mechanism of action myoclonus in PME forms has not yet been clearly understood. A study by Canafoglia et al. (9) showed more cortical irregularity in patients with sialidosis compared with patients with Unverricht-Lundborg disease. Presence of giant SEP waves, cortical potentials priming myocloni seen with back-averaging, C reflex, and decreased cortical inhibition with double-stimuli transcranial magnetic stimulation evaluation suggested these myocloni to be cortically originated. Moreover, although cranial MRI may be normal at an early period, and repeated MRIs show diffuse cortical atrophy, just like in our patient (10). PMEs may clinically resemble juvenile myoclonic epilepsy and with EEG findings, but treatment refractoriness, progressive neurologic and EEG findings lead to PME diagnosis. A basic activity consisting of fast rhythms may be seen in EEG, but slowing is more prominent in patients with dementia (8). Our patient also had mild slowing in EEG during her follow up for 14 years and neuropsychologic findings that supported mild dementia in recent years.

Treatment generally aims to stop seizures and myoclonus. Antiepileptic medications used to control myocloni are combinations of valproic acid, benzodiazepines, phenobarbital, piracetam, zonisamide, and levetiracetam. The effects of these drugs on myoclonus increase during the first 12 months and then stay steady. Additionally, drugs that increase myoclonus such as vigabatrine, carbamazepine, phenytoin, and gabapentin should be avoided. In the future, new management strategies such as gene treatment and enzyme replacement therapies are promising possible treatments (11,12). Our patient’s seizures were also controlled during the last year after with the addition of zonisamide to her treatment regime. Fundoscopic examination is important in patients who develop ataxia in the early ages. A “cherry-red spot” or perifoveal white patch can be detected in the fundoscopic examination. Although this phenomenon is a classic finding for sialidosis, it may also be seen in GM1 gangliosidosis, hexoseaminidase defect, and Nieman-Pick and Gaucher’s disease (13). In addition, a few cases were reported in which a “cherry-red spot” was not detected, despite the presence of a mutation in the NEU1 gene (6,9). We also could not detect “cherry-red spot” despite the presence of a NEU1 mutation; this documents the presence of a new phenotype in our country.

Conclusion

In conclusion, all evaluations for PMEs should be made in patients with progressive ataxia, refractory epilepsy, and myoclonus. A genetic evaluation should be performed in patients

with sialidosis whose clinical and electrophysiologic findings suggest PME, despite normal fundoscopic evaluation. Diagnosis is important for this rare form of hereditary sialidosis for which gene treatments may be possible in the future.

Ethics

Informed Consent: Consent form was filled out by participant.Peer-review: Externally peer-reviewed.


Medical Practices: Betül Baykan, Mikko Muona, Anna Elina Lehesjoki, Nerses Bebek, Candan Gürses, Ayşen Gökyiğit, Concept: Ebru Nur Vanlı Yavuz, Betül Baykan, Design: Ebru Nur Vanlı Yavuz, Betül Baykan, Güneş Altıokka, Data Collection or Processing: Ebru Nur Vanlı Yavuz, Betül Baykan, Analysis or Interpretation: Ebru Nur Vanlı Yavuz, Betül Baykan, Zeliha Matur, Literature Search: Ebru Nur Vanlı Yavuz, Güneş Altıokka, Writing: Ebru Nur Vanlı Yavuz, Betül Baykan, Zeliha Matur.

Conflict of Interest: No conflict of interest was declared by the authorsFinancial Disclosure: The authors declared that this study has received


References1. Ramachandran N, Girard JM, Turnbull J, Minassian BA. The autosomal

recessively inherited progressive myoclonus epilepsies and their genes. Epilepsia 2009;50 (Suppl 5):29-36.

2. Lai SC, Chen RS, Wu Chou YH, Chang HC, Kao LY, Huang YZ, Weng YH, Chen JK, Hwu WL, Lu CS. A longitudinal study of Taiwanese sialidosis type 1: An insight into the concept of cherry-red spot myoclonus syndrome. Eur J Neurol 2009;16:912-919.

3. Caciotti A, Di Rocco M, Filocamo M, Grossi S, Traverso F, d’Azzo A, Cavicchi C, Messeri A, Guerrini R, Zammarchi E, Donati MA, Morrone A. Type II sialidosis: Review of the clinical spectrum and identification of a new splicing defect with chitotriosidase assessment in two patients. J Neurol 2009;256:1911-1915.

4. Chen CM, Lai SC, Chen IC, Hsu KC, Lyu RK, Ro LS, Chang HS. First report of two Taiwanese siblings with sialidosis type I: A 10-year follow-up study. J Neurol Sci 2006;247:65-69.

5. Muona M, Berkovic SF, Dibbens LM, Oliver KL, Maljevic S, Bayly MA, Joensuu T, Canafoglia L, Franceschetti S, Michelucci R, Markkinen S, Heron SE, Hildebrand MS, Andermann E, Andermann F, Gambardella A, Tinuper P, Licchetta L, Scheffer IE, Criscuolo C, Filla A, Ferlazzo E, Ahmad J, Ahmad A, Baykan B, Said E, Topcu M, Riguzzi P, King MD, Ozkara C, Andrade DM, Engelsen BA, Crespel A, Lindenau M, Lohmann E, Saletti V, Massano J, Privitera M, Espay AJ, Kauffmann B, Duchowny M, Møller RS, Straussberg R, Afawi Z, Ben-Zeev B, Samocha KE, Daly MJ, Petrou S, Lerche H, Palotie A, Lehesjoki AE. A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy. Nat Genet 2015;47:39-46.

6. Lukong KE, Elsliger MA, Chang Y, Richard C, Thomas G, Carey W, Tylki-Szymanska A, Czartoryska B, Buchholz T, Criado GR, Palmeri S, Pshezhetsky AV. Characterization of the sialidase molecular defects in sialidosis patients suggests the structural organization of the lysosomal multienzyme complex. Hum Mol Genet 2000;9:1075-1085.

7. Canafoglia L, Robbiano A, Pareyson D, Panzica F, Nanetti L, Giovagnoli AR, Venerando A, Gellera C, Franceschetti S, Zara F. Expanding sialidosis spectrum by genome-wide screening: NEU1 mutations in adult-onset myoclonus. Neurology 2014;82:2003-2006.

8. Shahwan A Farrell M, Delanty N. Progressive myoclonic epilepsies: A review of genetic and therapeutic aspects. Lancet Neurol 2005;4:239-248.

9. Canafoglia L, Franceschetti S, Uziel G, Ciano C, Scaioli V, Guerrini R, Visani E, Panzica F. Characterization of severe action myoclonus in sialidoses. Epilepsy Res 2011;94:86-93.

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Turk J Neurol 2016;22:84-87Vanlı Yavuz et. al.; A Different Progressive Myoclonic Epilepsy: A Case Report

10. Sekijima Y, Nakamura K, Kishida D, Narita A, Adachi K, Ohno K, Nanba E, Ikeda S. Clinical and serial MRI findings of a sialidosis type I patient with a novel missense mutation in the NEU1 gene. Intern Med 2013;52:119-124.

11. Roivainen R, Karvonen MK, Puumala T. Seizure control in Unverricht-Lundborg disease: A single-centre study. Epileptic Disord 2014;16:191-195.

12. Striano P, Belcastro V. Treatment of myoclonic seizures. Expert Rev Neurother 2012;12:1411-1417.

13. Vieira de Rezende Pinto WB, Sgobbi de Souza PV, Pedroso JL, Barsottini OG. Variable phenotype and severity of sialidosis expressed in two siblings presenting with ataxia and macular cherry-red spots. J Clin Neurosci 2013;20:1327-1328.

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Images in Clinical Neurology / Klinik GörünümDO I:10.4274/tnd.90692Turk J Neurol 2016;22:88-89

A Case of Neuromyelitis Optica Presenting with Intractable Hiccups and Vomiting: Area Postrema Syndrome

Dirençli Kusma ve Hıçkırıkla Başlayan Bir Nöromiyelitis Optika Olgusu: Area Postrema Sendromu

Derya Kaya1, Egemen İdiman2, Fethi İdiman2, Onur Bulut2, Nuri Karabay3

1Dokuz Eylül University Faculty of Medicine, Division of Geriatrics, İzmir, Turkey2Dokuz Eylül University Faculty of Medicine, Department of Neurology, İzmir, Turkey3Dokuz Eylül University Faculty of Medicine, Department of Radiology, İzmir, Turkey

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Ad dress for Cor res pon den ce/Ya z›fl ma Ad re si: Derya Kaya MD, Dokuz Eylül University Faculty of Medicine, Division of Geriatrics, İzmir, Turkey Phone: +90 505 673 36 13 E-mail: [email protected]


Introduction

A woman aged 32 years was admitted to our clinic after she visited a gastroenterology center with symptoms of intractable hiccups and vomiting; no gastroenterologic pathology was found to explain her symptoms after a detailed examination. There were no other abnormalities in the patient's history except for intractable hiccups and vomiting that had lasted for about one month. A neurologic examination revealed no significant neuropathologic findings except hypoesthesia of the left half of the face in dermatomes of 2nd and 3rd branches of cranial nerve V, reduced deep sensation on the right side, and suspicious dysmetria on the left side of the body. Complete blood count, biochemical studies, C3, C4, C-reactive protein, sedimentation, electrolytes (Na, K, Cl) were within normal limits and vasculitic/immunologic tests were negative. Serum neuromyelitis optica-immunoglobulin G (NMO-IgG) was negative. A heterogeneous hyperintensity that extended from the medulla oblongata to the level of C3 and volume increase in the medulla oblongata and upper cervical region were observed on contrast-enhanced T2-weighted magnetic resonance images (MRI). Heterogeneous contrast enhancement was seen at the medulla oblongata and C1-C2 levels on post-contrast images (Figures 1a, b, c). MR spectroscopy was performed for the radiologic differential diagnosis of the medulla oblongata to determine whether there was tumor, inflammation, or ischemia; it was evaluated as inflammatory.

The patient underwent lumbar puncture and no oligoclonal bands were detected in the patient's cerebrospinal fluid. The IgG index was found as 0.63. One gram per day iv. methylprednisolone was administered for 10 days. The patient’s symptoms were completely recovered and she was discharged and requested to return for follow-up examinations.

One month later, the patient was admitted with symptoms of a tingling sensation that started from her back, spread up to her neck, and caused contractions in her arms at the same time. With the exception of Lhermitte's sign, the findings of a neurologic examination were within normal limits. Repeat cranial, cervical, and thoracic MRI revealed no new lesions; regression and loss of contrast enhancement was seen in the previous lesion that extended to the C2-C3 level, starting from the medulla oblongata. Serum samples were taken again for NMO-IgG analysis and NMO-IgG were found positive this time. Three mg/day azathioprine and 20 mg prednisolone tablet treatment was initiated with a diagnosis of NMO.

Although the presented case showed no involvement of two basic areas, optic nerve and spinal cord involvement, which are required according to the 2006 Wingerchuk criteria (1), the patient was diagnosed as having NMO spectrum disorders in accordance with the 2015 NMO criteria (2) because she was NMO-IgG positive and had one core clinical characteristic, area postrema involvement. Rapid and accurate diagnosis of patients

Keywords: Area postrema syndrome, neuromyelitis optica, neuromyelitis optica spectrum disordersAnahtar Kelimeler: Area postrema sendromu, neuromyelitis optika, nöromiyelitis optika spektrum hastalıkları

Turk J Neurol 2016;22:88-89Kaya et. al.; A Case of Neuromyelitis Optica Presenting with Area Postrema Syndrome

with atypical onset will ensure initiation of early treatment, prevention of future attacks, and permanent disability caused by the attacks.

Ethics

Informed Consent: Informed consent form was filled out by the case.Peer-review: Internal peer-reviewed.


Surgical and Medical Practices: Egemen İdiman, Fethi İdiman, Concept: Egemen İdiman, Design: Derya Kaya, Egemen İdiman, Data Collection or Processing: Onur Bulut, Derya Kaya, Nuri Karabay, Analysis or Interpretation: Derya Kaya, Egemen İdiman, Fethi İdiman, Literature Search: Onur Bulut, Derya Kaya, Writing: Derya Kaya, Egemen İdiman.



References 1. Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker

BG. Revised diagnostic criteria for neuromyelitis optica. Neurology 2006;66:1485-1489.

2. Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, de Seze J, Fujihara K, Greenberg B, Jacob A, Jarius S, Lana-Peixoto M, Levy M, Simon JH, Tenembaum S, Traboulsee AL, Waters P, Wellik KE, Weinshenker BG. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015;85:177-189.

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Figure 1. Brain and cervical magnetic resonance images of the patient. Centrally located hyperintense areas of demyelination extending from medulla oblongata to spinal cord (up to C3 vertebra level) and causing a slight expansion in the spinal cord on T2-weighted axial (a) and sagittal (b) magnetic resonance images. Heterogeneous contrast enhancement in the areas of demyelination on post-contrast sagittal T1-weighted magnetic resonance images (c)


Cystic Lesions in Spinal AstrocytomaSpinal Astrositomda Kistik Lezyonlar

Ahmet Evlice, Dilek İşcan, Meltem DemirkıranÇukurova University Faculty of Medicine, Department of Neurology, Adana, Turkey

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Ad dress for Cor res pon den ce/Ya z›fl ma Ad re si: Ahmet Evlice MD, Çukurova University Faculty of Medicine, Department of Neurology, Adana, Turkey Phone: +90 322 338 60 60-3206 E-mail: [email protected]


Introduction

Astrocytoma, which originates from uncontrolled growing glial cells, is the second most common tumor of the spinal cord after ependymoma in adults (1). It is more common in males, and the most common location is the cervical spinal cord, followed by the thoracic cord (2,3,4). Astrocytoma manifests with radicular pain and sensory loss. Motor deficits, spasticity, and sphincter dysfunction present in later stages (3,5). A patient with weakness of the legs in whom neuroimaging and histopathologic findings indicated a diagnosis of anaplastic astrocytoma is reported in this article.

A girl aged 17 years was admitted to our hospital with progressive weakness and numbness in the legs and urinary incontinence. The patient's neurologic evaluation revealed grade 4/5 paraparesis, hyperactive reflexes of the lower extremities, loss of sensation below the level of L1, loss of vibratory sense in the lower extremities, and bilateral Babinski signs. Spinal magnetic resonance imaging (MRI) showed multiple microcystic lesions at the levels of T5-9 in the epidural space, spinal cord edema, and myelomalacia T9 through T12 (Figure 1, 2, 3). A lumbar puncture was performed with a pre-diagnosis of myelitis. Protein level was 2549 mg/dL, glucose 71 mg/dL, lactate 4.9 mg/dL, and sodium 135 mEq/L in the cerebrospinal fluid and no cells were counted. A neurosurgical consultation was then ordered with a pre-diagnosis of spinal mass lesion. The patient underwent neurosurgery and a histopathologic evaluation of the specimen indicated a diagnosis of anaplastic astrocytoma. Lesions

of patients with astrocytoma in spinal MRI are hypointense or isointense in T1 and hyperintense in T2, as seen in our patient (Figure 1, 2, 3) (6). Cystic lesions are rare, and are difficult to distinguish from solid tumors because they contain high levels of protein (6,7). Our patient had multiple independent cystic lesions around the tumor. No other patients with these features have been

Keywords: Spinal, astrocytoma, cystAnahtar Kelimeler: Spinal, astrositom, kist

Figure 1. Spinal magnetic resonance imaging, T1-weighted sequences, sagittal plane

Turk J Neurol 2016;22:90-91Evlice et. al.; Cystic Lesions in Spinal Astrocytoma

reported in the literature. This patient was reported because she had uncharacteristic neuroimaging findings.

Ethics



Medical Practices: Ahmet Evlice, Dilek İşcan, Meltem Demirkıran, Concept: Ahmet Evlice, Dilek İşcan, Meltem Demirkıran, Design: Ahmet Evlice, Dilek İşcan, Meltem Demirkıran, Data Collection or Processing: Dilek İşcan, Analysis or Interpretation: Ahmet Evlice, Dilek İşcan, Meltem Demirkıran, Literature Search: Ahmet Evlice, Dilek İşcan, Meltem Demirkıran, Writing: Ahmet Evlice, Dilek İşcan, Meltem Demirkıran.


no financial support

References

1. Fischer G, Brotchi J, Chignier G, Liard A, Zomosa G, Menei P, Hallacq P: Epidemiology. In: Fischer G, Brotchi J (eds) Intramedullary spinal cord tumors. Thieme, Stuttgart, 1996, pp 9-10.

2. Minehan KJ, Shaw EG, Scheithauer BW, Davis DL, Onofrio BM. Spinal cord astrocytoma: Pathological and treatment considerations. J Neurosurg 1995;83:590-595.

3. Reimer R, Onofrio BM. Astrocytomas of the spinal cord in children and adolescents. J Neurosurg 1985;63:669-675.

4. Epstein F, Epstein N. Surgical management of holocord intramedullary spinal cord astrocytomas in children. J Neurosurg 1981;54:829-832.

5. Fischer G, Brotchi J. Intramedullary spinal cord tumors. Thieme, Stuttgart, 1996, pp 72-81.

6. Osborn AG. Diagnostic neuroradiology. Mosby, St. Louis, 1994, pp 906-914.

7. Horger M, Ritz R, Beschorner R, Fenchel M, Nägele T, Danz S, Ernemann U. Spinal pilocytic astrocytoma: MR imaging findings at first presentation and following surgery. Eur J Radiol 2011;79:389-399.

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Figure 2. Spinal magnetic resonance imaging, T2 weighted sequences, sagittal plane

Figure 3. Spinal magnetic resonance imaging, T2 weighted sequences, axial plane

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Ad dress for Cor res pon den ce/Ya z›fl ma Ad re si: Özlem Ethemoğlu MD, Harran University Faculty of Medicine, Department of Neurology, Şanlıurfa, Turkey Phone: +90 414 318 30 30 E-mail: [email protected]


Intracranial Hematoma in Herpes Simplex Encephalitis: A Rare Complication

Herpes Simpleks Ensefalitinde İntrakranyal Hematom: Nadir Bir Komplikasyon

Özlem Ethemoğlu1, Mehmet Fırat2, Kadri Burak Ethemoğlu3, Mehtap Kocatürk1

1Harran University Faculty of Medicine, Department of Neurology, Şanlıurfa, Turkey2Osm Middle East Private Hospital, Clinic of Infectious Diseases, Şanlıurfa, Turkey

3Harran University Faculty of Medicine, Department of Neurosurgery, Şanlıurfa, Turkey

Introduction

A previously healthy man aged 27 years was admitted to our hospital with a 2-day history of headache, confusion, and fever. The initial neurologic examination revealed impaired consciousness without seizures or focal neurologic deficits. Cerebrospinal fluid (CSF) analysis showed white blood cells 270/mm3 (87% lymphocytes, 13% neutrophils), protein level 132.6 mg/dL, and glucose 53 mg/dL (the synchronous serum value was 102 mg/dL). Other blood cell counts and the results of routine biochemical analysis were normal. CSF and blood cultures were negative. Electroencephalography showed right temporal focal slowing. CSF samples were positive for herpes simplex virus (HSV) 1 DNA in polymerase chain reaction, which confirmed the diagnosis of HSV-1 meningoencephalitis and antivirus treatment was started. The patient received intravenous acyclovir (30 mg/kg/day for 21 days) and dexamethasone (16 mg/day for 16 days). Brain computerized tomography (CT) performed on admission was normal (Figure 1). Brain magnetic resonance imaging performed on admission showed increased signal intensity in right temporal, inferior frontal, insular, and left medial temporal areas (Figure 2). Brain CT scan on day 2 showed a hematoma in the right medial temporal lobe with mass effect (Figure 3). The patient had no secondary clinical deterioration. Magnetic resonance angiography showed no aneurysm or vascular malformation. He remained asymptomatic on subsequent clinical follow-up.

Herpes simplex encephalitis (HSE) complicated by intracerebral hematoma is very unusual. It has been suggested that the rupture of small vessels affected by vasculitis causes secondary bleeding (1). Intracerebral hematoma may occur on admission or during hospitalization and even early treatment with acyclovir (2).

Keywords: Complication, intracranial hematoma, encephalitis, herpes simplexAnahtar Kelimeler: Komplikasyon, intrakranyal hematom, ensefalit, herpes simpleks

Figure 1. Brain computerized tomography on admission was normal

Turk J Neurol 2016;22:92-93Ethemoğlu et. al.; Intracranial Hematoma in Herpes Simplex Encephalitis

Intracerebral hematoma, which complicates HSE, is not always associated with poor outcomes. Secondary neurologic deterioration may be related to size, location, and mass effect of hematoma (3). HSE should be kept in mind in the etiology for patients who have symptoms typically suggestive of acute encephalitis and intracerebral hematoma.

Ethics



Concept: Özlem Ethemoğlu, Mehmet Fırat, Kadri Burak Ethemoğlu, Mehtap Kocatürk, Design: Özlem Ethemoğlu, Mehmet Fırat, Kadri Burak Ethemoğlu, Mehtap Kocatürk, Data Collection or Processing: Özlem Ethemoğlu, Kadri Burak Ethemoğlu, Analysis or Interpretation: Özlem Ethemoğlu, Literature Search: Ozlem Ethemoğlu, Writing: Özlem Ethemoğlu.

Conflict of Interest: This statement is to certify that all authors have seen and approved the manuscript being submitted. This case report has not been submitted for publication nor has it been published in whole or in part elsewhere. There is no conflict of interest in this paper. There were no external funding sources for this study.

References

1. Politei JM, Demey I, Pagano MA. Cerebral haematoma in the course of herpes simplex encephalitis. Rev Neurol 2003;36:636-639.

2. Fukushima Y, Tsuchimochi H, Hashimoto M, Yubi T, Nakajima Y, Fukushima T, Inoue T. A case of herpetic meningoencephalitis associated with massive intracerebral hemorrhage during acyclovir treatment: A rare complication. No Shinkei Geka 2010;38:171-176.

3. Shelley BP, Raniga SB, Al-Khabouri J. An unusual late complication of intracerebral haematoma in herpes encephalitis after successful acyclovir treatment. J Neurol Sci 2007;252:177-180.

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Figure 2. Brain magnetic resonance imaging axial T2-weighted image on admission showed increased signal intensity in the rhigt temporal lobe and left medial temporal lobe

Figure 3. Brain computerized tomography on day 2, demonstrating a hematoma in the right medial temporal lobe with mass effect

Frontiers in Neurology / Nörolojide Öne ÇıkanlarDO I:10.4274/tnd.26213Turk J Neurol 2016;22:94

An Approved Treatment in Periodic Paralyses: DiclorphenamidePeriyodik Paralizilerde Onaylanmış Bir Tedavi Seçeneği: Diklorfenamid

Mine Sezginİstanbul University İstanbul Faculty of Medicine, Department of Neurology, İstanbul, Turkey

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Ad dress for Cor res pon den ce/Ya z›fl ma Ad re si: Mine Sezgin MD, İstanbul University İstanbul Faculty of Medicine, Department of Neurology, İstanbul, Turkey Phone: +90 554 304 49 03 E-mail: [email protected]


An Approved Treatment in Periodic Paralyses: Diclorphenamide

Periodic paralyses (PP) are autosomal inherited muscle diseases that are directly associated with changes in serum potassium levels. Classified as channelopathies, PP are often triggered by exercise. Hyperkalemic periodic paralysis (HYP) is associated with mutations in SCN4A gene, and hypokalemic periodic paralysis (HOP) is associated with mutations in a calcium channel gene called CACNA1S and a sodium channel gene called SCN4A. PP becomes symptomatic in the first decade of life. The frequency of attacks in this group of diseases, which present with attacks, can be reduced by carbonic anhydrase inhibitors (acetazolamide and diclorphenamide) or potassium-sparing diuretics (1). Sansone et al. (2) showed in their randomized, multi-center, double-blind, placebo-controlled trial that diclorphenamide can be used in the treatment of PP with an evidence level of class 1. Forty-four patients with HYP and 21 with HOP were included in the trial. Two randomized, double-blind, placebo-controlled trials lasted 9 weeks, followed by a 1-year extension phase in which all participants received dichlorphenamide (DCP). The median attack rate, frequency of severe attacks, and the duration of attacks were lower in ptients with HYP on DCP. The median attack rate was also lower in patients with HOP on DCP compared with placebo, but without reaching statistical significance. There were

no significant effects of DCP on muscle strength or muscle mass in either trial. The most common adverse events were paresthesia, confusion, cognitive decline, and kidney stones. The median attack rate and frequency of severe attacks were increased in one patient with HOP on DCP with the NaV1.4pR222W mutation who had not previously used a carbonic anhydrase inhibitor; DCP treatment was stopped and the patient was excluded from the trial. The main shortcomings of these trials mentioned by the authors were the lack of comparison between DCP and acetazolamide and the limited number of participants, which precluded analysis by genetic subgroup. Finally, the Food and Drug Administration approved the use of DCP in HYP and HOP in August 2015.

Ethics


References1. Statland JM, Barohn RJ. Muscle channelopathies: the nondystrophic

myotonias and periodic paralyses. Continuum (Minneap Minn) 2013;19:1598-1614.

2. Sansone VA, Burge J, McDermott MP, Smith PC, Herr B, Tawil R, Pandya S, Kissel J, Ciafaloni E, Shieh P, Ralph JW, Amato A, Cannon SC, Trivedi J, Barohn R, Crum B, Mitsumoto H, Pestronk A, Meola G, Conwit R, Hanna MG, Griggs RC. Muscle study group. Randomized, placebo-controlled trials of dichlorphenamide in periodic paralysis. Neurology 2016;86:1408-1416.

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Frontiers in Neurology / Nörolojide Öne ÇıkanlarDO I:10.4274/tnd.79990Turk J Neurol 2016;22:95-96

Ad dress for Cor res pon den ce/Ya z›fl ma Ad re si: Halil İbrahim Akçay MD, İstanbul University Faculty of Medicine, Department of Neurology, İstanbul, Turkey Phone: +90 506 582 74 98 E-mail: [email protected]


Does Clopidogrel have an Effect on Migraine Attacks that Emerge after Closure of Atrial Septal Defects?

Klopidogrelin Atrial Septal Defekt Kapatılması Sonrası Ortaya Çıkan Migren Atakları Üzerine Etkisi var mı?

Halil İbrahim Akçay, Murat Kürtüncüİstanbul University Faculty of Medicine, Department of Neurology, İstanbul, Turkey

Does Clopidogrel have an Effect on Migraine Attacks that Emerge after Closure of Atrial Septal Defects?

New-onset migraine attacks occur in 15% of patients after transcatheter atrial septal closure. In these patients, migraine attacks start during the initial days or weeks. Antithrombotic treatment with aspirin is used for 6 months after closure. Early observational cross-sectional studies demonstrated that addition of clopidogrel to aspirin was associated with less frequent and milder migraine attacks.

The Clopidogrel for the Prevention of New-onset Migraine Headache Following Transchateter Closure of Atrial Septal Defects study by Rodés-Cabau et al. (1) was performed in 6 Canadian centers and included patients with atrial septal defect (ASD) aged 18 years and above who had a clinical indication for closure. Patients who had previous migraine, allergy or intolerance to antithrombotic drugs who needed anticoagulation, were pregnant or breast-feeding, or had a previous unsuccessful ASD closure procedure were excluded. Some patients only took aspirin 80 mg/day and the others took aspirin 80 mg/day and clopidogrel 75 mg/day. This treatment protocol was initiated one day before the ASD closure procedure and continued for 3 months. The patients did not receive a clopidogrel loading dose at the beginning. The patients kept a headache diary. The Migraine Disability Assessment Questionnaire was used to assess severity of headache. All migraine questionnaires and headache diaries were evaluated by two neurologists. The primary end point in this study was determined as the number of new-onset migraine attacks within 3 months of the ASD closure procedure. Secondary endpoints were the incidence of new-onset migraine attacks, the number of migraine attacks in the 1st and 3rd months, severity of migraine attacks, and time to the first migraine attack. The study included 291 patients who were treated between

2008-2014; 71 patients were excluded because they had a previous history of migraine. A total of 171 patients formed the study groups. Among them, 87 patients took aspirin plus placebo (the placebo group) and 84 patients took aspirin plus clopidogrel (the clopidogrel group). The results of the study showed that the mean monthly migraine number was lower in the clopidogrel group.

In summary, dual antiplatelet treatment for the initial three months after transcatheter ASD closure significantly decreased the number of new-onset migraine attacks and the probability of their occurrence. Moderate to severe migraine attacks were not seen in patients who were taking the dual treatment; however, one third of patients who only took aspirin had severe and disabling migraine attacks. Future research is needed to determine whether a longer duration of treatment is necessary. In another study, Spencer et al. (2) showed significant benefits of clopidogrel that was given before transcatheter closure on migraine in patients with patent foramen ovale who also had migraine. The benefits of specific antithrombotic treatments such as clopidogrel on decreasing occurrence of migraine attacks supports the idea that platelet and coagulation cascades are important in migraine pathogenesis. Other studies also showed that anticoagulant and antiplatelet (clopidogrel) use in special patient groups decreased migraine attacks. However, two randomized studies found no benefits of warfarin and clopidogrel in decreasing the frequency of migraine attacks (3,4).

This study showed that clopidogrel is highly protective against migraine attacks in the presence of specific triggers. Increased platelet aggregation was shown after ASD closure and as a result, release of pro-inflammatory cytokines such as interleukin (IL)-1, IL-6, and IL-8 and substances such as serotonin increased. These substances were found to be associated with migraine attacks. Clopidogrel has an antiplatelet effect in addition to antioxidant and anti-inflammatory features. The vaso-protective effect of

Turk J Neurol 2016;22:95-96 Akçay and Kürtüncü; Clopidogrel Effect on Migraine Patients with ASD Closure

clopidogrel by adenosine phosphate receptor blockage may play a role in preventing migraine attacks.

Ethics


References1. Rodés-Cabau J, Horlick E, Ibrahim R, Cheema AN, Labinaz M, Nadeem

N, Osten M, Côté M, Marsal JR, Rivest D, Marrero A, Houde C. Effect

of clopidogrel and aspirin vs aspirin alone on migraine headaches after transcatheter atrial septal defect closure: The CANOA randomized clinical trial. JAMA 2015;314:2147-2154.

2. Spencer BT, Qureshi Y, Sommer RJ. A retrospective review of clopidogrel as primary therapy for migraineurs with right to left shunt lesions. Cephalalgia 2014;34:933-937.

3. Wammes-van der Heijden EA, Smidt MH, Tijssen CC, van't Hoff AR, Lenderink AW, Egberts AC. Effect of low-intensity acenocoumarol on frequency and severity of migraine attacks. Headache 2005;45:137-143.

4. Chambers JB, Seed PT, Ridsdale L. Clopidogrel as prophylactic treatment for migraine: a pilot randomised, controlled study. Cephalalgia 2014;34:1163-1168.

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Meeting Highlights / Kongre ve Toplantılardan İzlenimlerDO I:10.4274/tnd.88896Turk J Neurol 2016;22:97-98

Ad dress for Cor res pon den ce/Ya z›fl ma Ad re si: Uğur Uygunoğlu MD, İstanbul University Cerrahpaşa Faculty of Medicine, Department of Neurology, İstanbul, Turkey Phone: +90 532 282 39 88 E-mail: [email protected]


Uğur Uygunoğlu, Melih Tütüncüİstanbul University Cerrahpaşa Faculty of Medicine, Department of Neurology, İstanbul, Turkey

The American Academy of Neurology (AAN) 68th Annual Meeting was held in Vancouver, BC, Canada, April 15th-21st, 2016. In this article, we summarize new developments and promising future studies that were presented during the congress.One of the most exciting studies presented at the congress was a study that reported the results of gene therapy in childhood cerebral adrenoleukodystrophy. The study was designed to improve the production of functional ALDP by autologous hematopoietic stem cells transduced with the lentiviral vector Lenti-D encoding ABCD1 cDNA. Seventeen patients had been included in this ongoing phase 2/3 trial so far, and 94% of the patients had stable neurologic function scores and imaging at 6 months with 2-year follow-up in three of these patients. It was stated that a serious drug-related adverse event (grade 3 viral cystitis) was observed in one patient and a probable drug-related adverse event (grade 2 tachycardia) had occurred in another, but these findings were reported to regress in both patients with standard treatments.

Trials on ‘Calcitonin Gene-Related Peptide’ in the treatment of episodic migraine were at the forefront. Three monoclonal antibody trials related to the peptide adrenoleukodystrophy (ALD) (LY2951743, ALD403, TEV-48125) and one monoclonal antibody trial related to the receptor (AMG 334) were discussed. The mean decrease in the duration of headaches in these studies was as follows: 4.2 days in a phase 2 LY2951743 trial that evaluated a subcutaneous injection every 2 weeks for 12 weeks (3 days in the placebo group), 5.6 days in the active headache group in a phase 2 ALD403 trial (4.6 days in the placebo group), and 3.4 days in a phase 2 AMG 334 trial that evaluated monthly subcutaneous injections (2.3 days in the placebo group).

It was shown that the combination of idalopirdine, an antagonist of the serotonin 5-HT6 receptor, and donepezil was more potent than donepezil monotherapy in patients with

moderate Alzheimer's disease. In this 24-week-long phase 2 double-blind study, 278 patients were randomly allocated to combination therapy (30 mg idalopirdine/3 times a day), and the change-from-baseline in the Alzheimer's Disease Assessment Scale-cog total score was +1.38 in the monotherapy group and -0.77 in the idalopirdine group.

Another interesting study presented at the congress was about sports with obvious head trauma. In a study in 40 retired National Football League players, a decline in connections between brain regions was reported in 17 players and traumatic axonal injury in 12 players on diffusion tensor imaging, which is a technique based on the movement of water molecules.

Everolimus, which acts as an inhibitor of the mammalian target of rapamycin, was reported to reduce the frequency of seizures in patients with refractory tuberous sclerosis. In this phase 3 trial that evaluated higher doses (9 to 15 ng/mL) or lower doses (3 to 7 ng/mL) of everolimus in 366 patients, the findings indicated the superiority of both treatments versus placebo; approximately 40% and 15% vs. 29%, respectively, were reported.

Antipsychotic drug-related involuntary movements of the face and limbs were reported to improve greatly with valbenazine. In this randomized, phase 3 trial, the change-from-baseline in the Abnormal Involuntary Movement Scale was +0.1 in the placebo group and +3.2 in the 80mg valbenazine group (p<0.0001). In the same study, 40mg valbenazine showed less effect than 80 mg; however, with a statistically significantly greater effect compared with placebo (p=0.0021).

The results of ocrelizumab, which is an Anti-CD20+ monoclonal antibody, in patients with relapsing-remitting multiple sclerosis (MS) were presented within the scope of the OPERA I and OPERA II trials. It was specified that 48% of ocrelizumab-treated patients fulfilled the No Evidence of Disease

Turk J Neurol 2016;22:97-98 Uygunoğlu and Tütüncü; Meeting Highlights

Activity criteria and that this percentage was almost twice as much as in interferon-1β-treated patients. Other than this, the results of 732 patients with primary progressive MS included in the ORATORIO trial were presented as a poster. The results did not differ from the results of the 2015 European Committee for Treatment and Research in Multiple Sclerosis Congress, and the drug was shown to provide a 24% reduction in a 12-week clinical disability progression (hazard ratio=0.76, p=0.0321).

An abstract was presented on clemastine fumarate, a widely-used antihistamine, on the restoration of demyelination in the optic nerve. The effect of the drug on remyelination and its potential effect in progressive MS, which has no treatment, was discussed. However, it was stated that somnolence and fatigue-causing effects of the drug, as with all antihistamines, might limit its use in patients with MS.

The updated AAN guidelines were presented, which take into account all publications on the use of botulinum neurotoxin in blepharospasm, cervical dystonia, adult spasticity, and headache since 2008. According to the new guidelines, 4 types

of botulinum neurotoxin (onabotulinum toxin A, abobotulinum toxin A, incobotulinum toxin A and rimabotulinum toxin B) were reported to act in these 4 different diseases at different levels. It was emphasized that three botulinum toxin A preparations were effective in upper limb spasticity (level of evidence I), and that abobotulinum toxin A and onabotulinum toxin A also had significant effects in lower limb spasticity (level of evidence I). Unlike the 2008 guidelines, information on the use of botulinum toxin in headache features in this guideline.

A presentation was made on dichlorphenamide, which was recently approved in the treatment of periodic paralysis. It was reported that the drug reduces relapse duration and frequency by 80% to 90% in this rare genetic disease with a prevalence of 1/100 000. Paresthesia and cognitive impairment were stated as adverse events.

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