case report cerebellar cognitive affective syndrome

Case ReportCerebellar Cognitive Affective Syndrome Presented as SevereBorderline Personality Disorder

Danilo Pesic1 Amir Peljto1 Biljana Lukic1 Maja Milovanovic1

Snezana Svetozarevic2 and Dusica Lecic Tosevski13

1 Institute of Mental Health Palmoticeva 37 11000 Belgrade Serbia2Department of Psychology Faculty of Philosophy University of Belgrade Cika Ljubina 18-20 11000 Belgrade Serbia3 Belgrade University School of Medicine Dr Subotica 8 11000 Belgrade Serbia

Correspondence should be addressed to Danilo Pesic pesicdaniloyahoocom

Received 8 December 2013 Accepted 5 February 2014 Published 11 March 2014

Academic Editor Marie-Cecile Nassogne

Copyright copy 2014 Danilo Pesic et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

An increasing number of findings confirm the significance of cerebellum in affecting regulation and early learning Most consistentfindings refer to association of congenital vermis anomalies with deficits in nonmotor functions of cerebellum In this paperwe presented a young woman who was treated since sixteen years of age for polysubstance abuse affective instability and self-harming who was later diagnosed with borderline personality disorder Since the neurological and neuropsychological reportspointed to signs of cerebellar dysfunction and dysexecutive syndrome we performed magnetic resonance imaging of brainwhich demonstrated partially developed vermis and rhombencephalosynapsis These findings match the description of cerebellarcognitive affective syndrome and show an overlap with clinical manifestations of borderline personality disorder

1 Introduction

There are an increasing number of findings supporting thefact that cerebellum apart from its significance in movementcoordination (sensomotoric cerebellum) plays an importantrole in cognitive and emotional regulation (cognitive andlimbic cerebellum) [1] In comparison with malformations ofother parts of cerebellum and the acquired lesions congenitalvermis deficit presents as pronounced slow psychomotordevelopment and worse cognitive functioning (lower IQ)and language skills as well as affective dysregulation [2]Rhombencephalosynapsis (RS) is a rare congenital posteriorfossa malformation characterised by hypogenesis or agenesisof the vermis dorsal fusion of cerebellar hemispheres andfusion of the dentate nuclei and superior cerebellar peduncles[3]

This paper presents a case of a patient diagnosed withborderline personality disorder (BPD) BrainMRIwhichwasperformed because of severe clinical picture and neurologicaland cognitive deficits showed partially developed vermis

and rhombencephalosynapsis This sheds a new light on theseverity of and nonresponsiveness to medication

2 Case Report

Unemployed single 26-year-old woman with a qualificationin catering industry living with parents was admitted fortreatment to the Institute of Mental Health in Belgrade afterone of her multiple suicide attempts by self-poisoning withbenzodiazepines She had been repeatedly hospitalized sinceshe was 16 at first because of polysubstance abuse and laterbecause of self-destructive behaviour affective instability andimpulsiveness and had been diagnosed with BPD Over thepast few years psychotropic medications were discontinuedHowever she was unable to get a job and establish anemotional relationshipOne year prior to admission to the thelatest hospitalization she started abusing benzodiazepinesand alcohol again culminating in a fall and short hospi-talization for brain commotion with normal computerised

Hindawi Publishing CorporationCase Reports in MedicineVolume 2014 Article ID 894263 4 pageshttpdxdoiorg1011552014894263

2 Case Reports in Medicine

tomography of brain Afterwards there were no signs ofacute or chronic complications of craniocerebral injury noremotional and behavioural changes regarding prior state Weacquired data that her mother had a virus infection in thefirst trimester of pregnancywith scanty hemorrhageDeliverywas vaginal with labour induction and the baby girl hada pronounced physiological jaundice Because of hypotoniarehabilitation was performed She was able to stand on herown at 15 months and to walk at 18 months and was notmanually dexterous Convergent strabismus was operatedwhen she was two years old Her attachment pattern wasambivalent There is a positive heredity on her fatherrsquos sideone uncle is being treated for depressive disorder and anotherone for bipolar affective disorder

Upon admission the patient showed difficulty in fitting inand it was impossible to establish a therapeutic alliance Shemanifested affective instability was irritable and verbalisedsuicidal ideas During therapeutic weekends she stereotypi-cally inflicted self-harm by cutting her forearm skin and bypressing cigarette butts in her hand dorsum

Physical examination has not shown any signs of illnessesand common laboratory test values were within referencevalues Thyroid function tests were normal The dominantfinding in neurological status was truncal ataxia Total scoreon the scale for the assesment and rating of ataxia [4] was 14out of 40 with dominant findings on stance (5 out of 6) gait(38) and sitting (24) Convergent strabismus and bilaterallyabsent corneal reflexes were also registered as well as a smallfield of temporoparietal left-sided alopecia

Psychological examination confirmed borderline person-ality organization with borderline depression and persistentsuicidal risk associated with primary impulse discontrolIntellectual capacities were at the border of low averageoverall IQ was 80 verbal IQ was 84 and manual IQ was73 The examination emphasized the fact that protrusivenegativism was activated regardless of the trigger and thatdifficulties in attaining aims were possibly also caused byneuropsychologically founded experiential learning capacityreduction

Various combinations of mood stabilisers and antide-pressants together with the second-generation antipsychoticswere administered without mood stabilization and reced-ing of suicidal ideation A partial response was noted toadministration of fluoxetine (40mg daily) together witholanzapine (15mg daily) All this led us to a decision to per-form neuropsychological examination electroencephalogra-phy (EEG) and MRI

Neuropsychological examination showed disturbances incomplex forms of attention with unfavourable reflection onphonemic fluency and verbal declarative memory with thepresence of retroactive inhibition and dysexecutive syndromewhich affect working memory impede orientation in initialtasks and reduce benefits fromprevious experience A reduc-tion in categorical fluency and dysnomia was evidencedConstructional praxis was distorted by parietal type dynamicdyspraxia was evidenced to the left as well as graphesthesiacontralaterally (Table 1)

The EEGwas normalTheMRI has shown partially devel-oped vermis and fusion of cerebellar hemispheres which

Figure 1Magnetic resonance imaging of brainwhich demonstratedpartially developed vermis and rhombencephalosynapsis

was a characteristic of RS (Figure 1) There were no signsof hydrocephalus nor any other central nervous system andextracentral nervous system malformations The MRI resultscould explain neurological and neuropsychological findingsand presence of ldquocerebellar cognitive affective syndromerdquo [5]as well as the persistance of mental health problems

Taking into consideration the pharmacoresistance andthe high sucidal risk clozapine (150mg daily) clomipramine(100mg daily) and lithium carbonate (900mg daily) wereintroduced with careful titrating because of potential neuro-toxicity and worsening of ataxia This resulted in receding ofsuicidal ideation partial affective stabilization better impulsecontrol and abandoning of self-destructive behaviour where-upon the patient was transferred to the out-patient treatmentAt the followup her condition is still characterized by affectiveinstability and impulsiveness but without self-harming andsuicidal attempts several months later

3 Disscussion

Limbic cerebellum is represented by vermis and fastigialnucleus and cognitive cerebellum by lateral hemispheres ofposterior cerebellum [1] Acquired and congenital lesionsof these regions lead to development of nonmotor deficitstermed ldquocerebellar cognitive affective syndromerdquo (CCAS)[5] It is characterized by disturbances of executive func-tions visual-spatial disorganization emotional dysregulation(blunting of affect and disinhibited and inadequate behavior)and language deficits (agrammatism and aprosodia) [5]

Impaired social interaction aggressiveness pervasivedisturbance of behaviour and self-harming are also moreoften noted in patients with vermis agenesis [2] It should bestressed that there are studies which do not show associationof acquired lesions of cerebellum with CCAS but onlyminor cognitive and affective changes However they also

Case Reports in Medicine 3

Table 1 Neuropsychological assessment

Test Patient Normative Data DeviationsWMS-R Verbal memory 7 7 plusmn 2 WMS-R Visual memory 3 7 plusmn 2 minus200 SDWMS-R AttentionConcentrationIndex 52 gt70 sec lt10 Pr

TMT-A 82 lt45 sec lt10 PrTMT-B 197 lt98 sec lt10 PrRAVLT 119905 26 553 plusmn 66 minus444 SDRAVLT 119890 2 140 plusmn 20 minus600 SDRAVLT 119903 12 144 plusmn 08 minus300 SDPhonemic fluency tests for divergentthinking S8 K11 L7 Min 8

Categorical fluency tests for divergentthinking 11 1958 plusmn 40 minus215 SD

RCF C 27 351 plusmn 15 minus540 SDRCF 401015840 40 227 plusmn 70 minus267 SDHVOT 21556ndash60 41ndash55 Low possibility of impairmentWCST CA 0 56 plusmn 10 minus560 SDWCST PR 30 13 plusmn 91 +186 SDWCST FMS 0 08 plusmn 13 NABNT 50 5586 plusmn 286 minus204 SDBDAE auditory comprehension 11 112 plusmn 11 minus018 SDBDAE total sentence repetition LP 78 77 plusmn 06 minus117 SDIdeomotor praxia 88 78Spatial aspects of praxia 1010 810

Dynamic praxia D 8 8ndash10 Left side impairmentL 5 (3 errors)

Tactile gnosia D 33 23L 33

Graphesthesia D 15 45 Right side impairmentL 55

VITI-IQVIQ 84 9986 plusmn 1498 minus105 SDPIQ 73 9937 plusmn 1466 minus180 SDFSIQ 80 9919 plusmn 1523 minus126 SD

Wechsler Memory Scale-Revised (WMS-R) Trail Making Test A and B (TMT-A and -B) Rey Auditive Verbal Learning Test (RAVLT) RAVLT 119905 total numberof repeated words in five attempts in the RAVLT RAVLT 119890 number of repeated words after 30 min (evocation) in the RAVLT and RAVLT 119903 number ofcorrectly recognized words (recognition) in the RAVLT Rey-Osterrieth Complex Figure Test (RCF) RCF C copying of the RCF and RCF 401015840 40-minutedelayed recall trial Hooper Visual Organization Test (HVOT)Wisconsin Card Sorting Test (WCST)WCST CA categories achieved in theWCSTWCST PRperseverative responses in the WCST and WCST FMS failures to maintain set in the WCST Boston Naming Test (BNT) Boston Diagnostic Aphasia Battery(BDAE) Serbian version of Wechsler Adult Intelligence Scale (WAIS)mdashldquoVekslerov Individualni Test Inteligencijerdquo (VITI) verbal IQ (VIQ) performance IQ(PIQ) and full scale IQ (FSIQ)

confirm that CCAS is a consistent finding for congenitalmalformations [6]

Rhombencephalosynapsis was first described in 1916 afterthe autopsy of a young man who committed suicide [7] Itcan occur as an isolated anomaly or together with differentsyndromes [3] Apart from hypotonia stereotypical headmovements and strabismus a clinical picture often includesattention disturbance hyperactivity and impulsiveness [7]Verri et al [8] have described a patient with mild mental

retardation obsessive-compulsive personality disorder andoral self-mutilations Nonsyndromic rhombencephalosynap-sis can rarely be asymptomatic and associated with normalneuropsychological findings [7]

Our patient manifested trunk ataxia and in the earlydevelopment she had hypotonia and developmental dys-praxia Pronounced affective instability dysphoria impul-siveness and self-harmful behaviour as well as the dysexec-utive syndrome and decrease of working memory together


with phonemic fluency reduction match the description ofCCAS as described by Schmahmann [5]

Bilaterally absent corneal reflexes and a small field oftemporoparietal left-sided alopecia were also interestingfindings but there were not enough criteria for diagnos-ing Gomez-Lopez-Hernandez syndrome which includesrhombencephalosynapsis trigeminal anesthesia and bilat-eral alopecia [9]

Numerous neuropsychiatric manifestations which canappear together with cerebellar lesions have been describedand can be classified in several domains attention distur-bances emotional control disturbances and disturbanceswhich belong to autistic spectrum and psychotic disorders[10] These disturbances could be explained both by connec-tions with limbic system and prefrontal cortex [1] and thesupposed role of cerebellum in social cognition and forminga theory of mind that is the ability to attribute mentalstates to others Positron emission tomography in healthyvolunteers showed a pronounced cerebellar activation whileperforming tasks which require activation of brain areas incharge of theory of mind [11] Taking into considerationthe fact that the concept of mentalization was formed byapplying the concept of the theory of mind in patients withborderline personality disorder by adding to the objectiveand cognitive concept of theory of mind a subjective andaffective component [12] we could assume that cerebellardysfunction could play a role in thementalization problem aswell

On the other hand fMRI studies showed that process-ing of negative emotions in patient with BPD was asso-ciated with greater activation within insula and posteriorcingulate cortex as well as anterior culmen and poste-rior declive of the cerebellum and reduced activation ofregion that extended from the amygdala to the subgenualanterior cingulate cortex and dorsolateral prefrontal cortex[13] Two questions remain whether activation of vermisis primary or compensatory mechanism in BDP patientsand how vermal hypoplasia can influence BPD phenotypeexpression

We should also take into consideration the possibilitythat some subradiographic cerebral hemisphere or limbicabnormalities could be present and contribute to the clinicalpicture in this case

The presented case shows an overlap between BPD andCCAS and suggests the importance of neurological and neu-ropsychological evaluation of patients with severe personalitydisorders

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

The authors thank the patient and her family for givingpermission to publish this report

References

[1] C J Stoodley and JD Schmahmann ldquoEvidence for topographicorganization in the cerebellum of motor control versus cogni-tive and affective processingrdquo Cortex vol 46 no 7 pp 831ndash8442010

[2] A Tavano R Grasso C Gagliardi et al ldquoDisorders of cognitiveand affective development in cerebellar malformationsrdquo Brainvol 130 no 10 pp 2646ndash2660 2007

[3] G E Ishak J C Dempsey D W W Shaw et al ldquoRhomben-cephalosynapsis a hindbrain malformation associated withincomplete separation of midbrain and forebrain hydro-cephalus and a broad spectrum of severityrdquo Brain vol 135 no5 pp 1370ndash1386 2012

[4] T Schmitz-Hubsch S Tezenas Du Montcel L Baliko andR Fancellu ldquoScale for the assessment and rating of ataxiadevelopment of a new clinical scalerdquo Neurology vol 66 no 8pp 1717ndash1720 2006

[5] J D Schmahmann ldquoDisorders of the cerebellum ataxia dysme-tria of thought and the cerebellar cognitive affective syndromerdquoJournal of Neuropsychiatry and Clinical Neurosciences vol 16no 3 pp 367ndash378 2004

[6] D Timmann and I Daum ldquoHow consistent are cognitiveimpairments in patients with cerebellar disordersrdquoBehaviouralNeurology vol 23 no 1-2 pp 81ndash100 2010

[7] A Poretti F D Alber S Burki S P Toelle and E BoltshauserldquoCognitive outcome in children with rhombencephalosynap-sisrdquo European Journal of Paediatric Neurology vol 13 no 1 pp28ndash33 2009

[8] A Verri C Uggetti E Vallero M Ceroni and A FedericoldquoOral self-mutilation in a patient with rhombencephalosynap-sysrdquo Journal of Intellectual Disability Research vol 44 no 1 pp86ndash90 2000

[9] B Sukhudyan V Jaladyan G Melikyan J U Schlump EBoltshauser and A Poretti ldquoGomez-Lopez-Hernandez syn-drome reappraisal of the diagnostic criteriardquo European Journalof Pediatrics vol 169 no 12 pp 1523ndash1528 2010

[10] J D Schmahmann J B Weilburg and J C Sherman ldquoTheneuropsychiatry of the cerebellummdashinsights from the clinicrdquoCerebellum vol 6 no 3 pp 254ndash267 2007

[11] C Calarge N C Andreasen and D S OrsquoLeary ldquoVisualizinghow one brain understands another a PET study of theory ofmindrdquo The American Journal of Psychiatry vol 160 no 11 pp1954ndash1964 2003

[12] LWChoi-Kain and JGGunderson ldquoMentalization ontogenyassessment and application in the treatment of borderlinepersonality disorderrdquo The American Journal of Psychiatry vol165 no 9 pp 1127ndash1135 2008

[13] A C Ruocco S Amirthavasagam L W Choi-Kain and S FMcMain ldquoNeural correlates of negative emotionality in border-line personality disorder an activation-likelihood-estimationmeta-analysisrdquo Biological Psychiatry vol 73 pp 153ndash160 2013

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tomography of brain Afterwards there were no signs ofacute or chronic complications of craniocerebral injury noremotional and behavioural changes regarding prior state Weacquired data that her mother had a virus infection in thefirst trimester of pregnancywith scanty hemorrhageDeliverywas vaginal with labour induction and the baby girl hada pronounced physiological jaundice Because of hypotoniarehabilitation was performed She was able to stand on herown at 15 months and to walk at 18 months and was notmanually dexterous Convergent strabismus was operatedwhen she was two years old Her attachment pattern wasambivalent There is a positive heredity on her fatherrsquos sideone uncle is being treated for depressive disorder and anotherone for bipolar affective disorder

Upon admission the patient showed difficulty in fitting inand it was impossible to establish a therapeutic alliance Shemanifested affective instability was irritable and verbalisedsuicidal ideas During therapeutic weekends she stereotypi-cally inflicted self-harm by cutting her forearm skin and bypressing cigarette butts in her hand dorsum

Physical examination has not shown any signs of illnessesand common laboratory test values were within referencevalues Thyroid function tests were normal The dominantfinding in neurological status was truncal ataxia Total scoreon the scale for the assesment and rating of ataxia [4] was 14out of 40 with dominant findings on stance (5 out of 6) gait(38) and sitting (24) Convergent strabismus and bilaterallyabsent corneal reflexes were also registered as well as a smallfield of temporoparietal left-sided alopecia

Psychological examination confirmed borderline person-ality organization with borderline depression and persistentsuicidal risk associated with primary impulse discontrolIntellectual capacities were at the border of low averageoverall IQ was 80 verbal IQ was 84 and manual IQ was73 The examination emphasized the fact that protrusivenegativism was activated regardless of the trigger and thatdifficulties in attaining aims were possibly also caused byneuropsychologically founded experiential learning capacityreduction

Various combinations of mood stabilisers and antide-pressants together with the second-generation antipsychoticswere administered without mood stabilization and reced-ing of suicidal ideation A partial response was noted toadministration of fluoxetine (40mg daily) together witholanzapine (15mg daily) All this led us to a decision to per-form neuropsychological examination electroencephalogra-phy (EEG) and MRI

Neuropsychological examination showed disturbances incomplex forms of attention with unfavourable reflection onphonemic fluency and verbal declarative memory with thepresence of retroactive inhibition and dysexecutive syndromewhich affect working memory impede orientation in initialtasks and reduce benefits fromprevious experience A reduc-tion in categorical fluency and dysnomia was evidencedConstructional praxis was distorted by parietal type dynamicdyspraxia was evidenced to the left as well as graphesthesiacontralaterally (Table 1)

The EEGwas normalTheMRI has shown partially devel-oped vermis and fusion of cerebellar hemispheres which

Figure 1Magnetic resonance imaging of brainwhich demonstratedpartially developed vermis and rhombencephalosynapsis

was a characteristic of RS (Figure 1) There were no signsof hydrocephalus nor any other central nervous system andextracentral nervous system malformations The MRI resultscould explain neurological and neuropsychological findingsand presence of ldquocerebellar cognitive affective syndromerdquo [5]as well as the persistance of mental health problems

Taking into consideration the pharmacoresistance andthe high sucidal risk clozapine (150mg daily) clomipramine(100mg daily) and lithium carbonate (900mg daily) wereintroduced with careful titrating because of potential neuro-toxicity and worsening of ataxia This resulted in receding ofsuicidal ideation partial affective stabilization better impulsecontrol and abandoning of self-destructive behaviour where-upon the patient was transferred to the out-patient treatmentAt the followup her condition is still characterized by affectiveinstability and impulsiveness but without self-harming andsuicidal attempts several months later

3 Disscussion

Limbic cerebellum is represented by vermis and fastigialnucleus and cognitive cerebellum by lateral hemispheres ofposterior cerebellum [1] Acquired and congenital lesionsof these regions lead to development of nonmotor deficitstermed ldquocerebellar cognitive affective syndromerdquo (CCAS)[5] It is characterized by disturbances of executive func-tions visual-spatial disorganization emotional dysregulation(blunting of affect and disinhibited and inadequate behavior)and language deficits (agrammatism and aprosodia) [5]

Impaired social interaction aggressiveness pervasivedisturbance of behaviour and self-harming are also moreoften noted in patients with vermis agenesis [2] It should bestressed that there are studies which do not show associationof acquired lesions of cerebellum with CCAS but onlyminor cognitive and affective changes However they also

























Acknowledgment


References



















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of








































Acknowledgment


References



















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















case report cerebellar cognitive affective syndrome

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