mog antibody positive, benign, unilateral, cerebral cortical … · aoki received research support...

Ryo Ogawa MDIchiro Nakashima MD

PhDToshiyuki Takahashi

MD PhDKimihiko Kaneko MDTetsuya Akaishi MDYoshiki Takai MD PhDDouglas Kazutoshi Sato

MD PhDShuhei Nishiyama MD

PhDTatsuro Misu MD PhDHiroshi Kuroda MD

PhDMasashi Aoki MD PhDKazuo Fujihara MD

PhD

Correspondence toDr Nakashimanakashimamedtohokuacjp

MOG antibodyndashpositive benignunilateral cerebral cortical encephalitiswith epilepsy

ABSTRACT

Objective To describe the features of adult patients with benign unilateral cerebral corticalencephalitis positive for the myelin oligodendrocyte glycoprotein (MOG) antibody

Methods In this retrospective cross-sectional study after we encountered an index case of MOGantibodyndashpositive unilateral cortical encephalitis with epileptic seizure we tested for MOGantibody using our in-house cell-based assay in a cohort of 24 consecutive adult patients withsteroid-responsive encephalitis of unknown etiology seen at Tohoku University Hospital (2008ndash2014) We then analyzed the findings in MOG antibodyndashpositive cases

Results Three more patients as well as the index case were MOG antibodyndashpositive and all wereadult men (median age 37 years range 23ndash39 years) The main symptom was generalized epi-leptic seizure with or without abnormal behavior or consciousness disturbance Two patients alsodeveloped unilateral benign optic neuritis (before or after seizure) In all patients brain MRIdemonstrated unilateral cerebral cortical fluid-attenuated inversion recovery hyperintense le-sions which were swollen and corresponded to hyperperfusion on SPECT CSF studies showedmoderate mononuclear pleocytosis with some polymorphonuclear cells and mildly elevated totalprotein levels but myelin basic protein was not elevated A screening of encephalitis-associatedautoantibodies including aquaporin-4 glutamate receptor and voltage-gated potassium channelantibodies was negative All patients received antiepilepsy drugs and fully recovered after high-dose methylprednisolone and the unilateral cortical MRI lesions subsequently disappeared Nopatient experienced relapse

Conclusions These MOG antibodyndashpositive cases represent unique benign unilateral cortical enceph-alitis with epileptic seizure The pathology may be autoimmune although the findings differ from MOGantibodyndashassociated demyelination and Rasmussen and other known immune-mediated encephalitidesNeurol Neuroimmunol Neuroinflamm 20174e322 doi 101212NXI0000000000000322

GLOSSARYADEM 5 acute disseminated encephalomyelitis AMPA 5 a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptorAQP4 5 aquaporin-4 CASPR2 5 contactin-associated protein 2 CBA 5 cell-based assay CBC 5 complete blood countCFF 5 critical flicker frequency DWI 5 diffusion-weighted imaging EAE 5 experimental autoimmune encephalomyelitisFLAIR 5 fluid-attenuated inversion recovery GABAB 5 g-aminobutyric acid receptor type B receptor GAD 5 glutamic aciddecarboxylase GdT1WI 5 gadolinium enhancement on T1-weighted imaging HIMP 5 high-dose IV methylprednisoloneHSV 5 herpes simplex virus IgG 5 immunoglobulin G IL-6 5 interleukin-6 LETM 5 longitudinally extensive transversemyelitis LGI1 5 leucine-rich glioma-inactivated protein 1 MBP 5 myelin basic protein MOG 5 myelin oligodendrocyteglycoprotein MS 5 multiple sclerosis NMDAR 5 NMDA receptor NMOSD 5 neuromyelitis optica spectrum disorderON 5 optic neuritis PSL 5 prednisolone RE 5 Rasmussen encephalitis T2WI 5 T2-weighted imaging Tg 5 thyroglobulinTPO 5 thyroid peroxidase VA 5 visual acuity VEP 5 visual evoked potential

Myelin oligodendrocyte glycoprotein (MOG) is a myelin protein expressed at the outermostlamellae of the myelin sheath in the CNS1ndash3 MOG is also used as an immunogen for exper-imental autoimmune encephalomyelitis (EAE)2ndash5 EAE studies have suggested that MOG

From the Department of Neurology (RO IN TT KK TA YT DKS SN TM HK MA KF) Tohoku University GraduateSchool of Medicine Sendai Department of Neurology (TT) Yonezawa National Hospital Yamagata Japan Brain Institute (DKS) ThePontifical Catholic University of Rio Grande do Sul Porto Alegre Brazil Department of Multiple Sclerosis Therapeutics (KF) FukushimaMedical University and Multiple Sclerosis amp Neuromyelitis Optica Center (KF) Southern Tohoku Research Institute for NeuroscienceKoriyama Japan

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This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 40 (CCBY-NC-ND) which permits downloading and sharing the work provided it is properly cited The work cannot be changed in any way or usedcommercially without permission from the journal

Neurologyorgnn Copyright copy 2017 The Author(s) Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology 1

antibodies play a direct pathogenetic role inthe animal model of inflammatory demyelin-ating disease although previous studies de-signed to detect MOG antibody with theELISA or Western blotting in human inflam-matory demyelinating diseases have failed toreveal any characteristic findings in pa-tients367 However recent studies have dem-onstrated that conformation-sensitive MOGantibody can be detected by cell-based assays(CBAs) in patients without multiple sclerosis(MS) such as those with pediatric acutedisseminated encephalomyelitis (ADEM)

aquaporin-4 (AQP4)ndashimmunoglobulin G(IgG)ndashnegative neuromyelitis optica spectrumdisorders (NMOSD) optic neuritis (ON)and longitudinally extensive transverse myeli-tis (LETM)238ndash12 These findings suggest thatthe MOG antibody may serve as a biomarkerto define a spectrum of inflammatory demy-elinating diseases and extensive studies ofMOG antibodyndashpositive cases may identifynew clinical phenotypes directly or indirectlyassociated with this myelin antibody

In the present study we encountered anindex case of MOG antibodyndashpositive

Table 1 Clinical features of 4 patients with unilateral cortical encephalitis positive for the MOG antibody

Patient 1 (index case) Patient 2 Patient 3 Patient 4

Sexage at onset y M39 M36 M23 M38

Clinical manifestations

Encephalopathy

Epileptic seizure Generalized tonicseizure with Toddpalsy

Generalized tonicseizure

Involuntary movement of theleft hand generalized tonicseizure

Generalized tonic seizureinitially involved the righthand

Disturbance ofconsciousness

Delirium Only in seizure Disorientation Only in seizure

Abnormal behavior andpsychiatric symptoms

Paranoia hallucinationanorexia

mdash mdash Agitation violent behavior

Other focal brainsymptoms

mdash mdash mdash Aphasia and righthemiparesis

Optic neuritis 1 (R 7 monthsbefore seizure)

1 (R after seizure) mdash mdash

Myelitis mdash mdash mdash mdash

Brain MRI

FLAIR hyperintensity R frontoparietal cortex R frontoparietalcortex

R parietal cortex L hemisphere cortex

ADEM-like brain lesion mdash mdash mdash mdash

CSF at acute phase

Cell countsmL (monopoly)

29 (236) 63 (621) 101 (5150) 311 (129182)

Protein mgdL 35 38 86 53

Oligoclonal IgG bands No data mdash mdash mdash

MBP pgmL No data 313 313 313

MOG antibody titer

Serum (onset) 1512 12048 1256 11024

Serum (remission) 116 1128 mdash mdash

CSF 132 14 116 No sample

Treatment HIMP PSL CBZ LTG HIMP PSL CBZ DEX PSL CBZ HIMP PSL CBZ

Response to treatments Full recovery afterHIMP

Full recovery afterHIMP

Full recovery after DEX Full recovery after HIMP

Relapse No No No No

Duration of follow-up mo 30 40 23 72

Abbreviations ADEM 5 acute disseminated encephalomyelitis CBZ 5 carbamazepine DEX 5 dexamethasone FLAIR 5

fluid-attenuated inversion recovery HIMP 5 high-dose IV methylprednisolone IgG 5 immunoglobulin G LTG 5 lamotrigineMBP 5 myelin basic protein MOG 5 myelin oligodendrocyte glycoprotein PSL 5 prednisolone

2 Neurology Neuroimmunology amp Neuroinflammation

benign unilateral cerebral cortical encephalitismanifesting with generalized epileptic seizureand then investigated the presence of MOGantibody in an adult cohort of patients withsteroid-responsive encephalitis of unknownetiology to identify any unique features ofencephalitis in MOG antibodyndashpositive cases

METHODS Patients sera and CSF We encountered an

adult patient (index case case 1) with unique benign unilateral

cerebral cortical encephalitis manifesting with generalized epilep-

tic seizure and seropositivity for MOG antibody in 2014 To

explore any other cases with similar features we identified 24

consecutive patients diagnosed with steroid-responsive

encephalitis of unknown etiology seen at Tohoku University

Hospital from 2008 to 2014 The patients were older than 20

years and were followed for more than 19 months We defined

steroid-responsive encephalitis of unknown etiology as cases

with encephalopathy (epileptic seizure abnormal behavior

disturbance of consciousness or focal brain symptoms) that

responded to corticosteroid therapy and could not be explained

by fever systemic illnesses or postictal symptoms Additional

criteria included abnormal brain MRI and CSF findings during

the acute phase that were compatible with encephalitis and not

indicative of alternative CNS diseases Sera and CSF were

collected during the acute phases and were stored at 280degC In

some cases sera obtained during remission phases were also stored

Assays for autoantibodies We conducted live CBA for MOG

antibody based on our previous reports with modification (we

used anti-human IgG1 as the secondary antibody to avoid

nonspecific binding810) Briefly full-length MOG-expressing or

MOG-nonexpressing stable cell lines were incubated with a 116

dilution of serum and then incubated with a 1400 dilution of Alexa

Fluor 488 mouse anti-human IgG1 antibody (A10631 Thermo

Fisher Scientific Rockford IL) After cell immunostaining 2

investigators (RO and TT) who were blinded to patientsrsquo

data judged MOG antibody positivity by comparing the staining

results of MOG-expressing and MOG-nonexpressing cells In

MOG antibodyndashpositive samples the antibody titers were calcu-

lated by consecutive twofold dilutions to ascertain the maximum

dilution with positive staining Simultaneously M23-AQP4

antibody in the serum was tested by live CBA using Alexa Fluor

488 goat anti-human IgG (A11008 Thermo Fisher Scientific) as

the secondary antibody Anti-NMDA receptor (NMDAR)

antibody anti-a-amino-3-hydroxy-5-methyl-4-isoxazole propionic

acid receptor (AMPA) antibody anti-leucine-rich glioma-

inactivated protein 1 (LGI1) antibody anti-contactin-associated

protein 2 (CASPR2) antibody and anti-g-aminobutyric acid

receptor type B receptor (GABAB) antibody in the CSF were

tested by indirect immunofluorescence using commercially

available kits (Euroimmun Luumlbeck Germany)

Standard protocol approvals registrations and patientconsents This study was approved by the institutional ethics

committee and all patients provided written informed consent

RESULTS In addition to the index case 3 other pa-tients were found to be seropositive for MOG anti-body The clinical characteristics of these 4 patientsare summarized in table 1 All of these patients weremale and the median onset age was 34 years (range23ndash39) All of the patients experienced epileptic seiz-ures 3 showed abnormal behavior 2 patients hadON (figure 1) and 1 patient had dysuria but nopatient had myelopathy In CSF examinations themedian cell count was 83mL (range 29ndash311) andthe median protein concentration was 46 mgdL(range 35ndash86) Myelin basic protein (MBP) in CSFwas not elevated in any of the 3 patients (cases 1 2and 3) whose CSF samples were available although

Figure 1 Orbital MRI findings in cases 1 and 2

Hyperintensities on axial short T1 inversion recovery (A C) and gadolinium enhancement (BD) were seen in the right optic nerves in cases 1 (A B) and 2 (C D) suggesting unilateral opticneuritis

Figure 2 Brain MRI findings in case 1

When hospitalized with epileptic seizure the right hemispheric cortical region in case 1 wasfluid-attenuated inversion recovery hyperintense (A) (arrowheads) and partially gadoliniumenhanced Meanwhile hyperintensities in the cortical region were less evident on diffu-sion-weighted (B) apparent diffusion coefficient (C) T2-weighted (D) T1-weighted (E) andgadolinium enhancement on T1-weighted (F) MRI

Neurology Neuroimmunology amp Neuroinflammation 3

they were positive for MOG antibody in the CSFOn brain MRI examination all 4 cases showed uni-lateral hemispheric cortical hyperintense lesions influid-attenuated recovery (FLAIR) imaging (figure 2Aand figure 3 AndashC FndashH JndashR and T) None of theMOG antibodyndashnegative patients in our cohort ofencephalitis patients showed such FLAIR-hyperintensecortical lesions The 4MOG antibodyndashpositive patientswere treated with high-dose IV corticosteroids andantiepilepsy drugs and they fully recovered We alsoscreened for other encephalitis-related autoantibodiesincluding AQP4 NMDAR AMPA LGI1 CASPR2and GABAB antibodies but negative results wereobtained for all of the cases

Case presentation Case 1 (index case) A 38-year-oldman developed right eye pain and visual loss Hisvisual acuity (VA) was 30200 and the critical flickerfrequency (CFF) was 164 Hz (normal 35) in hisright eye He presented with a right relative afferentpupillary defect and color vision defect in the righteye Fundus examination revealed optic disc swellingin the right eye Regarding visual evoked potentials(VEP) the amplitude of P100 was reduced with

prolonged latency in the right eye (1206 ms) Thispatient was diagnosed with idiopathic ON (figure 1A and B) and treated with high-dose IV methylpred-nisolone (HIMP) (1000 mgd for 3 days) followedby an oral prednisolone (PSL) taper His visual symp-toms greatly improved soon after HIMP Sevenmonths later the patient acutely developed loss ofconsciousness and generalized tonic seizure and wasadmitted to our hospital On admission he was alertbut his left hand was weak due to Todd palsy Com-plete blood cell counts (CBC) and biochemistry werenormal A CSF study showed mild pleocytosis andelevated interleukin-6 (IL-6 726 pgmL normal40 pgmL) Glutamic acid decarboxylase (GAD)antibody thyroid peroxidase (TPO) antibody andthyroglobulin (Tg) antibody results were negative inthe serum but the MOG antibody test was positivein the serum (1512) and in the CSF (132) (table 1)EEG showed rhythmic slow waves in the right cere-bral hemisphere but no epileptic discharge in theinterictal stage Brain MRI scanned on the day ofepilepsy onset showed FLAIR hyperintensity in theright hemispheric cortical region and the corticallayer was mildly swollen (figure 3 AndashC) but did

Figure 3 Brain MRI and SPECT findings in cases 1ndash4

On admission fluid-attenuated inversion recovery (FLAIR) hyperintensity was seen in the unilateral cerebral cortex in cases1 (AndashC) 2 (FndashH) 3 (KndashN) and 4 (PndashR) (arrowheads) Brain SPECT showed hyperperfusion in those cerebral cortical regionswith FLAIR hyperintensity in cases 1 (D) 2 (I) and 4 (S) However the FLAIR hyperintensities in the cortical regionsdisappeared after more than 2 years (E J O T)


not show gadolinium enhancement on T1-weightedimaging (GdT1WI) Slight hyperintensity in theregions of diffusion-weighted imaging (DWI) andT2-weighted imaging (T2WI) were seen but were lessevident than in the FLAIR image (figure 2 AndashF)Brain SPECT showed hyperperfusion in the region (fig-ure 3D) Whole-body PET-CT scans showed no malig-nancy or inflammation We started carbamazepine (400mgd) and lamotrigine (25 mgd) but 1 week later thepatient developed delirium paranoia hallucination andanorexia His symptoms worsened despite risperidoneadministration Subsequently we made a presumptivediagnosis of autoimmune encephalitis to start HIMPtherapy and his symptoms disappeared within a fewdays Eight weeks after admission he was asymptomaticand therefore discharged He continued oral predniso-lone (15 mgd then gradually tapered to 4 mgd in 18months) carbamazepine and lamotrigine and experi-enced no relapse thereafter At 26months after dischargehis serum MOG antibody titer had decreased substan-tially (116) Brain MRI showed no residual lesions 30months after discharge (figure 3E)

Case 2 A 36-year-old man let out a strange noiseand lost consciousness for several minutes resultingin a one-car accident when he was driving a car Hewas admitted to a local hospital that day and was trea-ted with carbamazepine (400 mgd) Brain MRItaken on admission showed a FLAIR-hyperintensearea in the right parietal cortex After admission hetwice developed a generalized tonic seizure righteye pain with visual loss and dysuria He was thentransferred to our hospital Neurologic examinationshowed impaired right VA and dysuria but no signsof meningeal irritation His VA was normal butvisual field testing showed central scotoma TheCFF was 25 Hz and VEP revealed prolonged P100latency (1284 ms) CBC and blood biochemistry re-sults were normal while the MOG antibody test waspositive in the serum (12048) and in the CSF (14)(table 1) The GAD antibody TPO antibody andTg antibody tests were negative in the serum TheCSF study showed mild pleocytosis and moderatelyelevated IL-6 (840 pgmL) The EEG results werenormal when the patient was in the interictal stageOn MRI examination 3 weeks after onset the rightoptic nerve was swollen short T1 inversion recoveryhyperintense and gadolinium-enhanced (figure 1 Cand D) FLAIR hyperintensity in the right hemi-spheric cortex was seen and the corresponding corti-cal layer was slightly swollen (figure 3 FndashH) andpartially gadolinium-enhanced Meanwhile hyperin-tensity was less evident in DWI and T2WI in thecortical region but brain SPECT showed hyperper-fusion in the region (figure 3I) Whole-body PET-CTshowed no abnormal uptake suspicious of malignancyor inflammation With a presumptive diagnosis of

autoimmune encephalitis HIMP was administeredand both neurologic and ocular symptoms fullyresolved Four weeks after admission the patientwas discharged without any symptoms Oral PSL(25 mgd gradually tapered off in 2 years) and carba-mazepine (400 mgd) was continued and he did notexperience any relapse At 40 months after dischargethe MOG antibody titer was reduced (1128) andbrain MRI showed no residual lesions (figure 3J)

Case 3 A 23-year-old man with involuntary move-ment of the left hand was diagnosed with epilepsy andwas treated with carbamazepine (400 mgd) with noapparent effect One month later he developed a gen-eralized tonic seizure that lasted for 1 hour The fol-lowing month he was admitted to our hospital fora severe headache But he did not complain of visualimpairment Upon neurologic examination he wasdisoriented without neck stiffness Although theCBC and blood biochemistry results were normalthe MOG antibody test was positive in the serum(1256) and in the CSF (116) (table 1) The GADantibody TPO antibody and Tg antibody tests werenegative in the serum The EEG examination re-vealed rhythmic slow waves in the right hemisphereespecially in the right parietal region but no epilepticdischarge was seen in the interictal state Brain MRIscanned 1 month after the onset of epilepsy showedFLAIR hyperintensity in the right hemispheric corti-cal region (figure 3 KndashN) Abnormalities in theregion in DWI T2WI and GdT1WI were equivocalWhole-body CT showed no malignancy or inflam-mation VEP was not examined Tests for cytomega-lovirus antigen in the blood and Mycobacteriumtuberculosis (QuantiFERON) were negative andPCR for herpes simplex virus (HSV) gram stainsand culture results were negative in the CSF How-ever because we could not rule out CNS infectiousdisease we initially treated the patient with IV cef-triaxone isoniazid ethambutol acyclovir flucona-zole and dexamethasone (33 mgd) His symptomsdisappeared soon after the treatment and we sus-pected autoimmune encephalitis rather than CNSinfection Four weeks after admission he was dis-charged with no symptoms but oral prednisolone(15 mgd gradually tapered off in a year) and carba-mazepine (600 mgd) were continued Eighteenmonths later he had not experienced a relapse andthe MOG antibody was undetectable in the serumNo brain MRI lesions were seen 23 months afterdischarge (figure 3O)

Case 4 A 38-year-old man was admitted to a localhospital with headache and abnormal behavior (hewas unable to dress himself) After admission heexperienced a generalized tonic seizure and he wastransferred to our hospital Because the cause ofthe generalized tonic seizure was unknown despite


a diagnostic workup he was discharged 1 week later(carbamazepine was continued) However 35months after the first admission he developed a gen-eralized tonic seizure which initially involved theright hand He also had aphasia and right hemiparesisand was readmitted to our hospital Neurologic exam-ination revealed delirium emotional incontinenceaphasia and mild right hemiparesis He did not showocular symptoms during the course of disease The

CBC and blood biochemistry were normal but theMOG antibody test was positive in the serum(11024) (table 1) Serum GAD antibody TPO anti-body and Tg antibody tests were negative Brain MRIscanned 4 days after the second episode of epilepsyshowed FLAIR hyperintensity in the left hemisphericcortical region (figure 3 PndashR) Brain SPECT demon-strated hyperperfusion in the region (figure 3S)Whole-body PET-CT findings showed no malignancy

Table 2 Differential diagnosis of autoimmune or immune-mediated encephalopathy

Age y Sex Clinical manifestations Autoantibodies Brain MRI findings Treatments Prognosis

Present cases 23ndash39 All male Seizure in all abnormalbehavior psychiatricsymptoms or other focalbrain symptoms in somecases no cancer

MOG antibody FLAIR-hyperintenseunilateral cerebralcortical lesions noatrophy

HIMP AED Full recovery norelapse

ADEM18 Children andyoung adults(40 y)

Male 60 Altered consciousnessand behavior weaknessataxia cranial nervepalsy seizure feverheadache vomiting andmeningeal signs

MOG antibody50

T2FLAIR multiplelarge lesions (2 cm) inthe white matter basalganglia brainstemcerebellum and spinalcord

HIMP IVIg PLEX Full recovery in50ndash89

Rasmussenencephalitis17

Infancy toadulthood (mean6 y)

Nopredominance

Hemiparesis seizureand unilateral movementdisorder (athetosisdystonia)

GluR antibody insome cases

Unilateral hemisphericfocal cortical lesionswith atrophy

AED HIMP IVIgPLEX surgery

Severe fixedneurologicdeficit

NMDARencephalitis1819

8 monthsndash85years (mean21 y)

Femaledominant

Psychiatric disorderseizure movementdisorder autonomicinstability and centralhypoventilation ovarianteratoma usually foundin young women

NMDAR GluN1subunit antibody

Abnormal mainlymedial temporal lobelesions in half of cases

HIMP IVIg PLEXrituximab

80 recover orhave milddeficits

VGKC-Ab-associatedencephalopathy1820

47ndash77 years(median 63)

Male dominant Amnesia seizurepsychiatric disturbanceautonomic dysfunctionand neuromyotonia

LGI1 CASPR2antibodies

T2FLAIRhyperintensity in themedial temporal lobehippocampus oramygdala in half ofcases

HIMP PLEX IVIg Oftenmonophasic

GAD-Ab-associatedlimbic encephalitis21


Femaledominant

Epilepsy mild cognitivedisorder

GAD antibody(1000 UmL)

High signal on T2 inthe medial temporallobe or hippocampus

HIMP PLEX Chronic ornonremittingcourse

Other autoimmunelimbic encephalitis18

Hu antibody50ndash63 yearsMa2 antibody22ndash70 yearsAMPA receptorantibody 23ndash81years GABAB

receptor antibody16ndash77 years

Male dominantHu Ma2GABAB

receptorantibodiesfemaledominantAMPA receptorantibody

Confusion workingmemory deficit moodchange seizureassociated with tumors(ex small-cell lungcarcinoma testicularseminoma thymoma)

Hu Ma2 AMPAreceptor GABAB

receptorantibodies

FLAIRhyperintensities in themedial temporal lobe

HIMP IVIg PLEXtumor treatment

Differ accordingtoautoantibodiesbut rarely fullyrecover

Hashimotoencephalopathy22

23ndash83 years(mean 60 years)

Femaledominant

Seizure myoclonushallucination or stroke-episodes

Thyroidperoxidasethyroglobulinantibodiesa-enolaseantibody

Normal or nonspecificabnormalities

HIMP Improvement inmost patients

NMOSD102425 AQP4 antibodyndashpositive around40 years onaverage 1ndash2in children MOGantibodyndashpositive3ndash70 years(median 375years)

AQP4antibodyndashpositivefemale domi-nant (60ndash90) MOGantibodyndashpositive nofemalepreponderance

Optic neuritis acutemyelitis hiccups ornausea and vomitingacute brainstemsyndrome symptomaticnarcolepsy or acutediencephalic clinicalsyndrome symptomaticcerebral syndrome

AQP4 antibodyMOG antibody

AQP4 antibodyndashpositive dorsal medullaarea postrema peri-ependymal brainstemsubcortical or deepwhite matter corpuscallosum long cortico-spinal tract lesionsMOG antibody positiveADEM brainstemlesions

HIMP PLEX IVIgcyclophosphamide inacute attacksimmunosuppressantsfor relapse prevention

AQP4-positivemore than one-third could notwalk withoutunilateralassistanceMOG antibodyndashpositive rela-tively benign

Abbreviations ADEM 5 acute disseminated encephalomyelitis AED 5 antiepileptic drug AQP4 5 aquaporin-4 DWI 5 diffusion-weighed imaging FLAIR 5

fluid-attenuated inversion recovery GAD 5 glutamic acid decarboxylase HIMP 5 high-dose IV methylprednisolone IVIg 5 IV immunoglobulinMOG 5 myelin oligodendrocyte glycoprotein NMDAR 5 NMDA receptor NMOSD 5 neuromyelitis optica spectrum disorders PLEX 5 plasma exchangeVGKC 5 voltage-gated potassium channel


or swollen lymph nodes VEP was not done PCR forHSV gram stains and culture results were negative inthe CSF After admission his symptoms became worse(agitation and violent behavior) despite the administra-tion of sedatives We suspected autoimmune encepha-litis and started HIMP after which time he becameasymptomatic and was discharged He continued car-bamazepine (300 mgd) and experienced no relapse At84 months after discharge he was MOG antibody-negative A brain MRI taken 72 months after dischargewas normal (figure 3T)

DISCUSSION In the index case (case 1) we testedfor MOG antibody because the patient had unilateralbenign ON rather than unilateral cortical encephalitiswith epileptic seizure Then we tested for MOG anti-body in our cohort of 24 consecutive adult cases ofcorticosteroid-responsive encephalitis of unknownetiology and identified 3 additional patients withMOG antibody positivity Unexpectedly these 3MOG antibodyndashpositive patients also had unilateralcortical encephalitis with epileptic seizure as seen inthe index case and there were no cases of unilateralcortical encephalitis with epileptic seizure withoutMOG antibody positivity in our cohort The uni-lateral cortical lesions best depicted by FLAIR imageswere unique and appeared distinct from brain lesionspreviously described in MOG antibodyndashpositivediseases including ADEM13

The unilateral cortical lesions in our cases 1ndash4needed to be differentiated from seizure-induced brainMRI abnormalities14 Such brain MRI abnormalitiesinduced by epileptic seizure are localized in the corti-calsubcortical regions hippocampus basal gangliawhite matter or corpus callosum and they are readilyvisible on DWI due to cytotoxic changes1516 How-ever the MRI findings in our cases were much moreclearly seen in FLAIR images than in DWI and ADCfindings (figure 1 AndashF) Moreover pleocytosis in theCSF and a favorable response to HIMP suggested thatthe unique unilateral cortical lesions were inflamma-tory and hyperperfusion on SPECT corresponding tothe cortical FLAIR hyperintensity supported theinflammatory nature and epileptogenicity of the swol-len cortical lesions in the acute phase

We also ruled out a variety of autoantibody-mediated or immune-mediated encephalitides (table2) before we concluded that the unilateral corticalencephalitis with epileptic seizure in our cases wasunique Rasmussen encephalitis (RE) is described asunilateral cerebral cortical encephalitis similar to thatobserved in our patients However RE is clinicallycharacterized by focal epilepsy progressive hemiplegiaand cognitive decline with unilateral hemispheric focalcortical atrophy in the chronic stage and corticosteroidand other anti-inflammatory therapies are only partially

effective17 Our cases did not share these features of REor fulfill the diagnostic criteria The lesion distributionin our 4 patients was also dissimilar to the brainMRI abnormalities in cases of encephalitis with sei-zure associated with NMDAR antibody VGKCantibody GAD antibody and antithyroid antibod-ies18ndash22 and our patients were negative for thoseautoantibodies Likewise the clinical and neuroi-maging features of our cases were distinct from lim-bic encephalitides with positivity for GAD LGI1GABAB or AMPA antibodies18 and from the brainsyndrome previously described in NMOSD102324

FLAIR-hyperintense lesions localized at the cerebralcortex or sulcus similar to the findings observed in thepresent cases can develop in various CNS diseasesincluding meningitis subarachnoid hemorrhage lepto-meningeal metastasis acute infarction and moyamoyadisease25 In a review of such MRI abnormalities theleft temporo-occipital cortical FLAIR-hyperintense le-sions in a 23-year-old man with the diagnosis of men-ingitis appeared to be similar to the brain MRI findingsin our cases More recently Numa et al26 reporteda case of a 37-year-old woman who was diagnosed withADEM when she was 4 years old and developed ONfollowed by recurrent ADEM 33 years later She wasMOG antibodyndashpositive and brain MRI showedunique cortical FLAIR-hyperintense lesions in the lefttemporal and frontal lobes Thus unilateral corticalencephalitis in MOG antibodyndashpositive patients asin the 4 cases in our study may have been previouslyunnoted as a distinct phenotype The relationshipbetween MOG antibody and the unilateral cerebralcortical encephalitis observed in our cases remainsunclear Two of our patients had benign unilateral ONin which MOG antibody is often detected while cases3 and 4 lacked such characteristics of CNS diseasessuch as ON LETM NMOSD or ADEM237ndash10121327ndash29 Thus unilateral cerebral cortical encephalitismay be another characteristic manifestation of MOGantibodyndashpositive patients Although some cases ofMOG antibodyndashassociated diseases fulfill the diagnos-tic criteria of seronegative NMOSD23 the spectrum ofMOG antibodyndashassociated diseases is obviously widerthan NMOSD In the near future MOG antibodyndashassociated diseases may be recognized as a distinctclinical entity of inflammatory demyelinating diseasesof the CNS30

There is some evidence to support the pathogenicpotential of MOG antibody Experimental studieshave shown that MOG antibody can affect oligoden-drocytes and myelins3132 In addition in a few brain-biopsied cases of tumefactive brain lesions with MOGantibody positivity pathologic examinations revealedactive inflammatory demyelination with deposition ofimmunoglobulins and complement3334 or MS type IIpathology3536 Moreover we recently reported high


CSF-MBP levels without elevated CSF glial fibrillaryacidic protein levels an astrocytic damage marker inMOG antibodyndashpositive patients37 These findingssuggest that MOG antibody may directly contributeto inflammatory demyelination in antindashmyelinantibodyndashassociated CNS diseases However in 3 ofour MOG antibodyndashpositive cases whose CSF-MBPlevels were measured during the acute phase therewas no elevation in CSF-MBP despite the extensivecortical involvement and CSF pleocytosis Thus it isalso possible that MOG antibody itself may not bedirectly associated with the unilateral cerebral corticalencephalitis with epileptic seizure in our patients andthat another autoimmune disorder coexisting withMOG antibody positivity might be responsible forthe encephalitis In fact MOG antibody can bedetected in some patients with other autoantibody-associated encephalitides such as NMDAR antibodyndashpositive encephalitis38 In addition a pathogenicautoantibody may be generated years before the clinicalonset of disease as seen in AQP4 antibodyndashpositiveNMOSD39 Accordingly CNS lesions associated withMOG antibody may possibly develop later in thedisease course of cases 3 and 4 Therefore an unknownautoantibody might be associated with the unilateralcerebral cortical encephalitis with epileptic seizure ina fraction of MOG antibodyndashpositive cases althoughwe need to perform immunohistochemistry orimmunofluorescence with rodent brain tissue slicesand the sera and CSF from the patients as an attemptto see whether there are any antibody reactivities to thecerebral cortical tissues

Our study is retrospective and has some limita-tions Because our patient cohort was small and derivedfrom a single university hospital the results should beverified in prospective larger-scale multicenter studiesIn addition we analyzed only adult patients in the pres-ent study and it is important to determine whetherMOG antibodyndashpositive unilateral cerebral corticalencephalitis with epileptic seizure also occurs in chil-dren Therefore at this point it is premature to discussthe frequency of MOG antibodyndashpositive unilateralcerebral cortical encephalitis in corticosteroid-responsiveencephalitis of unknown etiology However since weexperienced 6 cases of NMDAR antibodyndashassociatedencephalitis and 1 with VGKC antibodyndashassociatedencephalitis during the same period (2008ndash2014)unilateral encephalitis with MOG antibody may not beso uncommon

Taken together we report a form of benign unilat-eral cerebral cortical encephalitis with epileptic seizurein 4 adult patients with MOG antibody positivityThe pathogenesis of this condition appears to beimmune-mediated or autoantibody-mediatedalthough the clinical MRI and laboratory featuresdiffer from those in previously described MOG

antibodyndashassociated CNS diseases39101340 andknown autoantibody-mediated encephalitides18

Another autoantibody that coexists with MOG anti-body may be responsible for this type of encephalitis

AUTHOR CONTRIBUTIONSRO analyzed the data and wrote the paper substantial contribution to

the study conception acquisition analysis and interpretation of data for

the work writing the manuscript drafting and correction of all versions

of the manuscript including figures tables and references completion of

the work to be submitted provided final approval of the version to be

published agreed to be accountable for all aspects of the work IN sub-

stantial contribution to the conception and design of the work as well as

supervision of the acquisition analysis and interpretation of data for the

work revised several versions of the manuscript critically for important

intellectual content provided final approval of the version to be pub-

lished agreed to be accountable for all aspects of the work TT substan-

tial contribution to the conception and design of the work as well as

supervision of the acquisition analysis and interpretation of data for

the work revised several versions of the manuscript critically for impor-

tant intellectual content provided final approval of the version to be pub-

lished agreed to be accountable for all aspects of the work KK

contribution to the plan of the work acquisition analysis interpretation

of data for the work and drafting the original manuscript related to the

case provided final approval of the version to be published agreed to be

accountable for all aspects of the work TA acquisition analysis and

interpretation of data for the work provided final approval of the version

to be published agreed to be accountable for all aspects of the work YT

acquisition analysis and interpretation of data for the work provided

final approval of the version to be published agreed to be accountable

for all aspects of the work DKS acquisition analysis and interpretation

of data for the work provided final approval of the version to be pub-

lished agreed to be accountable for all aspects of the work SN acqui-

sition analysis and interpretation of data for the work provided final

approval of the version to be published agreed to be accountable for

all aspects of the work TM acquisition analysis and interpretation of

data for the work provided final approval of the version to be published

agreed to be accountable for all aspects of the work HK substantial con-

tribution to the conception and design of the work as well as supervision of

the acquisition analysis and interpretation of data for the work revised sev-

eral versions of manuscript critically for important intellectual content pro-

vided final approval of the version to be published agreed to be accountable

for all aspects of the work MA substantial contribution to the conception

and design of the work as well as supervision of the acquisition analysis

and interpretation of data for the work provided final approval of the ver-

sion to be published agreed to be accountable for all aspects of the work

KF substantial contribution to the conception and design of the work as

well as supervision of the acquisition analysis and interpretation of data for

the work supervision of the manuscript preparation revised several versions

of the manuscript critically for important intellectual content final respon-

sibility and approval of the version to be published agreed to be account-

able for all aspects of the work

ACKNOWLEDGMENTThe authors thank Yuri Atobe and Kaori Tobise for technical assistance

STUDY FUNDINGThis study was partially supported by a grant-in-aid for scientific research

from the Japan Society for the Promotion of Science (KAKENHI) the

Health and Labour Sciences Research Grant on Intractable Diseases (neu-

roimmunologic diseases) from the Ministry of Health Labour and

Welfare of Japan

DISCLOSURESR Ogawa reports no disclosures I Nakashima received travel funding

and speaker honoraria from Biogen Japan Tanabe Mitsubishi and No-

vartis Pharma is on the editorial board for Multiple Sclerosis International

and received research support from LSI Medience Corporation

T Takahashi received speaker honoraria from Biogen Idec and Cosmic


Corporation and received research support from Cosmic Corporation K

Kaneko and T Akaishi report no disclosures Y Takai received research

support from Ministry of Education Culture Sports Science and Tech-

nology of Japan DK Sato served on the advisory board for Merck

Teva and Shire received speaker honoraria from Novartis Genzyme

Merck-Serono Biogen Teva Bayer and Roche is an associate editor

for Arquivos de Neuropsiquiatria and received research support from

Ministry of Education Culture Sports Science and Technology in

Japan Japan Society for the Promotion of Science and CAPESBrasil

S Nishiyama received research support from Japan Society for the

Promotion of Science T Misu received speaker honoraria from Bayer

Schering Pharma and Biogen Idec Japan and received research support

from Ministry of Education Culture Sports Science and Technology

Ministry of Health Labor and Welfare of Japan H Kuroda received

research support from Ministry of Education Culture Sports Science

and Technology of Japan M Aoki received research support from

Japanese Ministry of Health Labor and Welfare Japanese Ministry of

Education Culture Sports Science and Technology K Fujihara serves on

the advisory boards for Bayer Schering Pharma Biogen Idec Mitsubishi

Tanabe Pharma Corporation Novartis Pharma Chugai Pharmaceutical

Ono Pharmaceutical Nihon Pharmaceutical Alexion Pharmaceuticals and

Medimmune has received travel funding and speaker honoraria from Bayer

Schering Pharma Biogen Idec Eisai Inc Mitsubishi Tanabe Pharma

Corporation Novartis Pharma Astellas Pharma Inc Takeda Pharmaceutical

Company Limited Asahi Kasei Medical Co Daiichi Sankyo and Nihon

Pharmaceutical is on the editorial board for Clinical and Experimental

Neuroimmunology is an advisory board member for Sri Lanka Journal of

Neurology and received research support from Bayer Schering Pharma

Biogen Idec Japan Asahi Kasei Medical The Chemo-Sero-Therapeutic

Research Institute Teva Pharmaceutical Mitsubishi Tanabe Pharma Teijin

Pharma Chugai Pharmaceutical Ono Pharmaceutical Nihon Pharmaceutical

Genzyme Japan Ministry of Education Science and Technology of Japan

and Ministry of Health Welfare and Labor of Japan Go to Neurologyorgnn

for full disclosure forms

Received December 5 2016 Accepted in final form December 152016

REFERENCES1 Johns TG Bernard CC The structure and function of

myelin oligodendrocyte glycoprotein J Neurochem

1999721ndash9

2 Reindl M Di Pauli F Rostasy K Berger T The spectrum

of MOG autoantibody-associated demyelinating diseases

Nat Rev Neurol 20139455ndash461

3 Ramanathan S Dale RC Brilot F Anti-MOG antibody

the history clinical phenotype and pathogenicity of

a serum biomarker for demyelination Autoimmun Rev

201615307ndash324

4 Merkler D Schmelting B Czeh B Fuchs E Stadelmann C

Bruck W Myelin oligodendrocyte glycoprotein-induced

experimental autoimmune encephalomyelitis in the

common marmoset reflects the immunopathology of

pattern II multiple sclerosis lesions Mult Scler 2006

12369ndash374

5 Stassart RM Helms G Garea-Rodriguez E et al A new

targeted model of experimental autoimmune encephalo-

myelitis in the common marmoset Brain Pathol 2016

26452ndash464

6 Zhou D Srivastava R Nessler S et al Identification of

a pathogenic antibody response to native myelin oligoden-

drocyte glycoprotein in multiple sclerosis Proc Natl Acad

Sci USA 200610319057ndash19062

7 Lalive PH Hausler MG Maurey H et al Highly reactive

anti-myelin oligodendrocyte glycoprotein antibodies dif-

ferentiate demyelinating diseases from viral encephalitis

in children Mult Scler 201117297ndash302

8 Waters P Woodhall M OrsquoConnor KC et al MOG cell-

based assay detects non-MS patients with inflammatory

neurologic disease Neurol Neuroimmunol Neuroinflamm

20152e89 doi 101212NXI0000000000000089

9 Kitley J Waters P Woodhall M et al Neuromyelitis

optica spectrum disorders with aquaporin-4 and myelin-

oligodendrocyte glycoprotein antibodies a comparative

study JAMA Neurol 201471276ndash283

10 Sato DK Callegaro D Lana-Peixoto MA et al Distinc-

tion between MOG antibody-positive and AQP4

antibody-positive NMO spectrum disorders Neurology

201482474ndash481

11 Rostasy K Mader S Hennes EM et al Persisting myelin

oligodendrocyte glycoprotein antibodies in aquaporin-4

antibody negative pediatric neuromyelitis optica Mult

Scler 2013191052ndash1059

12 Jarius S Ruprecht K Kleiter I et al MOG-IgG

in NMO and related disorders a multicenter study of

50 patients part 2 epidemiology clinical presenta-

tion radiological and laboratory features treatment re-

sponses and long-term outcome J Neuroinflammation

201613280

13 Kim SM Woodhall MR Kim JS et al Antibodies to

MOG in adults with inflammatory demyelinating disease

of the CNS Neurol Neuroimmunol Neuroinflamm 2015

2e163 doi 101212NXI0000000000000163

14 Cianfoni A Caulo M Cerase A et al Seizure-induced

brain lesions a wide spectrum of variably reversible MRI

abnormalities Eur J Radiol 2013821964ndash1972

15 Chatzikonstantinou A Gass A Forster A Hennerici MG

Szabo K Features of acute DWI abnormalities related to

status epilepticus Epilepsy Res 20119745ndash51

16 Milligan TA Zamani A Bromfield E Frequency and pat-

terns of MRI abnormalities due to status epilepticus

Seizure 200918104ndash108

17 Varadkar S Bien CG Kruse CA et al Rasmussenrsquos

encephalitis clinical features pathobiology and treatment

advances Lancet Neurol 201413195ndash205

18 Graus F Titulaer MJ Balu R et al A clinical approach to

diagnosis of autoimmune encephalitis Lancet Neurol

201615391ndash404

19 Titulaer MJ McCracken L Gabilondo I et al Treatment

and prognostic factors for long-term outcome in patients

with anti-NMDA receptor encephalitis an observational

cohort study Lancet Neurol 201312157ndash165

20 Huda S Wong SH Pettingill P OrsquoConnell D Vincent A

Steiger M An 11-year retrospective experience of antibod-

ies against the voltage-gated potassium channel (VGKC)

complex from a tertiary neurological centre J Neurol

2015262418ndash424

21 Malter MP Helmstaedter C Urbach H Vincent A Bien

CG Antibodies to glutamic acid decarboxylase define a form

of limbic encephalitis Ann Neurol 201067470ndash478

22 Yoneda M Fujii A Ito A Yokoyama H Nakagawa H

Kuriyama M High prevalence of serum autoantibodies

against the amino terminal of alpha-enolase in Hashi-

motorsquos encephalopathy J Neuroimmunol 2007185

195ndash200

23 Wingerchuk DM Banwell B Bennett JL et al Interna-

tional consensus diagnostic criteria for neuromyelitis optica

spectrum disorders Neurology 201585177ndash189

24 Zekeridou A Lennon VA Aquaporin-4 autoimmunity

Neurol Neuroimmunol Neuroinflamm 20152e110 doi

101212NXI0000000000000110


25 Maeda M Yagishita A Yamamoto T Sakuma H Takeda K

Abnormal hyperintensity within the subarachnoid space eval-

uated by fluid-attenuated inversion-recovery MR imaging

a spectrum of central nervous system diseases Eur Radiol

200313(suppl 4)L192ndashL201

26 Numa S Kasai T Kondo T et al An adult case of

anti-myelin oligodendrocyte glycoprotein (MOG)

antibody-associated multiphasic acute disseminated

encephalomyelitis at 33-year intervals Intern Med

201655699ndash702

27 OrsquoConnor KC McLaughlin KA De Jager PL et al Self-

antigen tetramers discriminate between myelin autoantibodies

to native or denatured protein Nat Med 200713211ndash217

28 Brilot F Dale RC Selter RC et al Antibodies to native

myelin oligodendrocyte glycoprotein in children with

inflammatory demyelinating central nervous system disease

Ann Neurol 200966833ndash842

29 Huppke P Rostasy K Karenfort M et al Acute disseminated

encephalomyelitis followed by recurrent or monophasic optic

neuritis in pediatric patients Mult Scler 201319941ndash946

30 Zamvil SS Slavin AJ Does MOG Ig-positive AQP4-

seronegative opticospinal inflammatory disease justify

a diagnosis of NMO spectrum disorder Neurol

Neuroimmunol Neuroinflamm 20152e62 doi 10

1212NXI0000000000000062

31 Dale RC Tantsis EM Merheb V et al Antibodies to MOG

have a demyelination phenotype and affect oligodendrocyte

cytoskeleton Neurol Neuroimmunol Neuroinflamm 20141

e12 doi 101212NXI0000000000000012

32 Saadoun S Waters P Owens GP Bennett JL Vincent A

Papadopoulos MC Neuromyelitis optica MOG-IgG

causes reversible lesions in mouse brain Acta Neuropathol

Commun 2014235

33 Konig FB Wildemann B Nessler S et al Persistence of

immunopathological and radiological traits in multiple

sclerosis Arch Neurol 2008651527ndash1532

34 Spadaro M Gerdes LA Mayer MC et al Histopathology

and clinical course of MOG-antibody-associated encepha-

lomyelitis Ann Clin Transl Neurol 20152295ndash301

35 Lucchinetti C Bruck W Parisi J Scheithauer B Rodriguez M

Lassmann H Heterogeneity of multiple sclerosis lesions

implications for the pathogenesis of demyelination Ann Neurol

200047707ndash717

36 Spadaro M Gerdes LA Krumbholz M et al Autoanti-

bodies to MOG in a distinct subgroup of adult multiple

sclerosis Neurol Neuroimmunol Neuroinflamm 20163

e257 doi 101212NXI0000000000000257

37 Kaneko K Sato DK Nakashima I et al Myelin injury

without astrocytopathy in neuroinflammatory disorders

with MOG antibodies J Neurol Neurosurg Psychiatry

2016871257ndash1259

38 Titulaer MJ Hoftberger R Iizuka T et al Overlapping

demyelinating syndromes and anti-N-methyl-D-aspartate

receptor encephalitis Ann Neurol 201475411ndash428

39 Nishiyama S Ito T Misu T et al A case of NMO seropositive

for aquaporin-4 antibody more than 10 years before onset

Neurology 2009721960ndash1961

40 Baumann M Sahin K Lechner C et al Clinical and neuro-

radiological differences of paediatric acute disseminating

encephalomyelitis with and without antibodies to the myelin

oligodendrocyte glycoprotein J Neurol Neurosurg Psychiatry

201586265ndash272


DOI 101212NXI000000000000032220174 Neurol Neuroimmunol Neuroinflamm

Ryo Ogawa Ichiro Nakashima Toshiyuki Takahashi et al positive benign unilateral cerebral cortical encephalitis with epilepsyminusMOG antibody

This information is current as of January 16 2017

Academy of Neurology All rights reserved Online ISSN 2332-7812Copyright copy 2017 The Author(s) Published by Wolters Kluwer Health Inc on behalf of the AmericanPublished since April 2014 it is an open-access online-only continuous publication journal Copyright

is an official journal of the American Academy of NeurologyNeurol Neuroimmunol Neuroinflamm

ServicesUpdated Information amp

httpnnneurologyorgcontent42e322fullhtmlincluding high resolution figures can be found at

References httpnnneurologyorgcontent42e322fullhtmlref-list-1

This article cites 40 articles 3 of which you can access for free at

Citations httpnnneurologyorgcontent42e322fullhtmlotherarticles

This article has been cited by 2 HighWire-hosted articles

Subspecialty Collections

httpnnneurologyorgcgicollectionmriMRI

httpnnneurologyorgcgicollectionautoimmune_diseasesAutoimmune diseases

httpnnneurologyorgcgicollectionall_epilepsy_seizuresAll EpilepsySeizures

httpnnneurologyorgcgicollectionall_demyelinating_disease_cnsAll Demyelinating disease (CNS)following collection(s) This article along with others on similar topics appears in the

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httpnnneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in

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antibodies play a direct pathogenetic role inthe animal model of inflammatory demyelin-ating disease although previous studies de-signed to detect MOG antibody with theELISA or Western blotting in human inflam-matory demyelinating diseases have failed toreveal any characteristic findings in pa-tients367 However recent studies have dem-onstrated that conformation-sensitive MOGantibody can be detected by cell-based assays(CBAs) in patients without multiple sclerosis(MS) such as those with pediatric acutedisseminated encephalomyelitis (ADEM)

aquaporin-4 (AQP4)ndashimmunoglobulin G(IgG)ndashnegative neuromyelitis optica spectrumdisorders (NMOSD) optic neuritis (ON)and longitudinally extensive transverse myeli-tis (LETM)238ndash12 These findings suggest thatthe MOG antibody may serve as a biomarkerto define a spectrum of inflammatory demy-elinating diseases and extensive studies ofMOG antibodyndashpositive cases may identifynew clinical phenotypes directly or indirectlyassociated with this myelin antibody

In the present study we encountered anindex case of MOG antibodyndashpositive

Table 1 Clinical features of 4 patients with unilateral cortical encephalitis positive for the MOG antibody

Patient 1 (index case) Patient 2 Patient 3 Patient 4

Sexage at onset y M39 M36 M23 M38

Clinical manifestations

Encephalopathy

Epileptic seizure Generalized tonicseizure with Toddpalsy

Generalized tonicseizure

Involuntary movement of theleft hand generalized tonicseizure

Generalized tonic seizureinitially involved the righthand

Disturbance ofconsciousness

Delirium Only in seizure Disorientation Only in seizure

Abnormal behavior andpsychiatric symptoms

Paranoia hallucinationanorexia

mdash mdash Agitation violent behavior

Other focal brainsymptoms

mdash mdash mdash Aphasia and righthemiparesis

Optic neuritis 1 (R 7 monthsbefore seizure)

1 (R after seizure) mdash mdash

Myelitis mdash mdash mdash mdash

Brain MRI

FLAIR hyperintensity R frontoparietal cortex R frontoparietalcortex

R parietal cortex L hemisphere cortex

ADEM-like brain lesion mdash mdash mdash mdash

CSF at acute phase

Cell countsmL (monopoly)

29 (236) 63 (621) 101 (5150) 311 (129182)

Protein mgdL 35 38 86 53

Oligoclonal IgG bands No data mdash mdash mdash

MBP pgmL No data 313 313 313

MOG antibody titer

Serum (onset) 1512 12048 1256 11024

Serum (remission) 116 1128 mdash mdash

CSF 132 14 116 No sample

Treatment HIMP PSL CBZ LTG HIMP PSL CBZ DEX PSL CBZ HIMP PSL CBZ

Response to treatments Full recovery afterHIMP

Full recovery afterHIMP

Full recovery after DEX Full recovery after HIMP

Relapse No No No No

Duration of follow-up mo 30 40 23 72

Abbreviations ADEM 5 acute disseminated encephalomyelitis CBZ 5 carbamazepine DEX 5 dexamethasone FLAIR 5

fluid-attenuated inversion recovery HIMP 5 high-dose IV methylprednisolone IgG 5 immunoglobulin G LTG 5 lamotrigineMBP 5 myelin basic protein MOG 5 myelin oligodendrocyte glycoprotein PSL 5 prednisolone











































































MOG antibody50





Nopredominance








Femaledominant














Femaledominant












receptorantibodies






Femaledominant















































































Welfare of Japan












































1999721ndash9







201615307ndash324






12369ndash374




26452ndash464




Sci USA 200610319057ndash19062








20152e89 doi 101212NXI0000000000000089








201482474ndash481










201613280




2e163 doi 101212NXI0000000000000163















201615391ndash404









2015262418ndash424








195ndash200






101212NXI0000000000000110











201655699ndash702















1212NXI0000000000000062




e12 doi 101212NXI0000000000000012




Commun 2014235










200047707ndash717




e257 doi 101212NXI0000000000000257




2016871257ndash1259











201586265ndash272




















Reprints













































































MOG antibody50





Nopredominance








Femaledominant














Femaledominant












receptorantibodies






Femaledominant















































































Welfare of Japan












































1999721ndash9







201615307ndash324






12369ndash374




26452ndash464




Sci USA 200610319057ndash19062








20152e89 doi 101212NXI0000000000000089








201482474ndash481










201613280




2e163 doi 101212NXI0000000000000163















201615391ndash404









2015262418ndash424








195ndash200






101212NXI0000000000000110











201655699ndash702















1212NXI0000000000000062




e12 doi 101212NXI0000000000000012




Commun 2014235










200047707ndash717




e257 doi 101212NXI0000000000000257




2016871257ndash1259











201586265ndash272




















Reprints




































































Welfare of Japan












































1999721ndash9







201615307ndash324






12369ndash374




26452ndash464




Sci USA 200610319057ndash19062








20152e89 doi 101212NXI0000000000000089








201482474ndash481










201613280




2e163 doi 101212NXI0000000000000163















201615391ndash404









2015262418ndash424








195ndash200






101212NXI0000000000000110











201655699ndash702















1212NXI0000000000000062




e12 doi 101212NXI0000000000000012




Commun 2014235










200047707ndash717




e257 doi 101212NXI0000000000000257




2016871257ndash1259











201586265ndash272




















Reprints









































1999721ndash9







201615307ndash324






12369ndash374




26452ndash464




Sci USA 200610319057ndash19062








20152e89 doi 101212NXI0000000000000089








201482474ndash481










201613280




2e163 doi 101212NXI0000000000000163















201615391ndash404









2015262418ndash424








195ndash200






101212NXI0000000000000110











201655699ndash702















1212NXI0000000000000062




e12 doi 101212NXI0000000000000012




Commun 2014235










200047707ndash717




e257 doi 101212NXI0000000000000257




2016871257ndash1259











201586265ndash272




















Reprints













201655699ndash702















1212NXI0000000000000062




e12 doi 101212NXI0000000000000012




Commun 2014235










200047707ndash717




e257 doi 101212NXI0000000000000257




2016871257ndash1259











201586265ndash272




















Reprints






















Reprints




mog antibody positive, benign, unilateral, cerebral cortical … · aoki received research support...

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