Prefrontal cortex dysfunction has been associated with a series of behavioral symptoms, such as impulsivity and affective instability, which are the defining features of several personality disorders, notably, borderline personality disorder. We report on a 27-year-old patient with schizencephaly in the right frontal lobe (cingulate cortex lesion and secondary orbitofrontal cortex dysfunction) presenting with prominent borderline features and compromise of executive functions, decision-making and attention. We hypothesize that the personality disorder of our patient could be related to cingulate cortex lesion and secondary orbitofrontal cortex dysfunction associated with schizencephaly

Cano Prais, Hugo Alejandro

Correa, Humberto

Diniz, Leandro Malloy

Rocha, Felipe Filardi da

Sousa, Karla Cristhina Alves de

Teixeira, Ant?nio L?cio

Clinical Neurology and Neurosurgery

REPOSITORIO INSTITUCIONAL DA UFOP

Aasbo©K1caitdtpbbdAtMSf0dClinical Neurology and Neurosurgery 110 (2008) 396–399Case reportBorderline personality features possibly related to cingulate andorbitofrontal cortices dysfunction due to schizencephalyFelipe Filardi da Rocha a, Leandro Malloy-Diniz b, Karla Cristhina Alves de Sousa c,Hugo Alejandro Cano Prais c, Humberto Correa c, Antonio Lucio Teixeira d,∗a Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazilb Neuropsychology and Neurosciences Research Group, Health Sciences School, FUMEC University, Belo Horizonte, Minas Gerais, Brazilc Department of Mental Health, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazild Department of Internal Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, BrazilReceived 28 August 2007; received in revised form 12 November 2007; accepted 13 December 2007bstractPrefrontal cortex dysfunction has been associated with a series of behavioral symptoms, such as impulsivity and affective instability, whichre the defining features of several personality disorders, notably, borderline personality disorder. We report on a 27-year-old patient withchizencephaly in the right frontal lobe (cingulate cortex lesion and secondary orbitofrontal cortex dysfunction) presenting with prominentorderline features and compromise of executive functions, decision-making and attention. We hypothesize that the personality disorder ofur patient could be related to cingulate cortex lesion and secondary orbitofrontal cortex dysfunction associated with schizencephaly.2007 Elsevier B.V. All rights reserved.tal corthbpb2foeywords: Schizencephaly; Impulsivity; Borderline personality; Orbitofron. IntroductionSchizencephaly (SCHZ) is a rare congenital disorder oferebral cortical development. SCHZ is characterized bybnormal slits or clefts in the brain’s cerebral hemispheres. Its a form of porencephaly in which there is a cyst or a cavity inhe cerebral hemispheres. An anomaly of neuronal migrationuring the second trimester of gestation period is consideredhe most likely explanation for schizencephaly [1].Lesions of the prefrontal region, mainly orbital and medialrefrontal cortices, have been associated with a series ofehavioral symptoms, such as impulsivity and affective insta-ility, which are the defining features of several personalityisorders, notably, borderline personality disorder (BPD) [2].lthough neuroimaging studies demonstrated differences inhe prefrontal cortex of patients with BPD compared to∗ Corresponding author at: Departamento de Clı́nica Médica, Faculdade deedicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190anta Efigênia, Belo Horizonte 30130-100, Brazil. Tel.: +55 21 34992651;ax: +55 21 34992651.E-mail address: altexr@gmail.com (A.L. Teixeira).firgsshpss303-8467/$ – see front matter © 2007 Elsevier B.V. All rights reserved.oi:10.1016/j.clineuro.2007.12.009ex; Cingulate cortexealthy subjects [2–4], there is no published report correlatingorderline features and SCHZ.We describe a patient with SCHZ in the right frontal loberesenting with a personality disorder marked by prominentorderline features.. Case reportA 27-year-old man was admitted to our psychiatric wardollowing a judicial order due to the involvement in episodesf aggression and attempted robbery.Behavioral problems of the patient were noticed for therst time when he was 8 years old. At this age, he startedecurrent fights with fellow pupils. During adolescence, heot involved in frequent episodes of exihibitionist behavior,ubstance abuse (i.e. sporadic marijuana and alcohol con-umption) and displays of temper and aggression directed atis family members. Besides impulsive behavior, he has alsoresented with affective instability, a persistently unstableense of self and a pattern of unstable and intense interper-onal relationships.ogy and Neurosurgery 110 (2008) 396–399 397NCIa(dtbfifcfaiv(ri(ICGt1pvaflctyWtwppimHCspmmwinBnFig. 1. T1-weighted magnetic resonance imaging showing unilateralschizencephaly (type 1) in the right frontal lobe: (A) axial image demon-smcta(cu3F.F. da Rocha et al. / Clinical NeurolTwo structured clinical interviews, Mini Internationaleuropsychiatric Interview (M.I.N.I.)-Plus and Structuredlinical Interview for DSM Personality Disorders (SCID)-I, were used to perform the diagnosis of DSM-IV Axis-Ind Axis-II disorders, respectively. Psychoactive drug abusemarijuana and alcohol) was identified but no other Axis-Iisorder, including bipolar disorder, was noticed. Based onhe patient’s long-term history of impulsivity, affective lia-ility and unstable sense of self and relationships, borderlineeatures could be easily identified. Other borderline features,ncluding transient paranoid ideation, feeling of emptiness orear of abandonment, were not evidenced.Careful laboratory investigation, including blood count,reatine kinase level, electrolytes, renal, liver and thyroidunction tests, serology for syphilis and HIV, was undertakennd all exams were unrevealing. Brain magnetic resonancemaging (MRI) showed unilateral SCHZ of the closed lipariety (type 1) with clefts located in the right frontal lobeFig. 1A and B).The patient was also submitted to a comprehensive neu-opsychological assessment of intelligence (Wechsler adultntelligence scale, third edition; WAIS-III) [5], attentionomission errors on Conners’ continuous performance testI; CPT-II) [6], motor impulsiveness (commission errors onPT-II) [6], decision-making/cognitive impulsiveness (Iowaambling Task; IGT) [7], constructional ability (copy ofhe Rey Osterreich complex figure; SPREEN & STRAUSS,998), visual memory (retrieval of the Rey Osterreich com-lex figure), verbal learning and memory (Rey auditoryerbal learning test; RAVLT) [8], and language (verbal IQnd verbal comprehension indexes of WAIS-III and worduency) [5,8].His performance on the neuropsychological tests wasompared to the performance of asymptomatic male con-rols matched for age (mean ± S.D., years; 28.2 ± 1.4) andears of formal education (mean ± S.D., years; 7.3 ± 1.2).hen the results of the patient differed two standard devia-ions above or bellow the mean value of control group theyere considered altered.He presented with normal intellectual level, although hiserformance was worse than in asymptomatic controls in theerformance scale IQ, working memory and speed processingndexes of the WAIS-III (Table 1). There was no impair-ent of memory, language and visuoconstructional abilities.e committed several commission and omission errors onPT-II indicating compromise of attention and motor impul-ivity, respectively. He also was more susceptible to effects ofroactive interference on learning process. On IGT, he madeore non-profitable choices suggesting deficits in decision-aking.The result of his neuropsychological assessment is in lineith the clinical symptoms presented by the patient, notablympulsivity. As the patient had SCHZ, he could not be diag-osed as BPD. According to DSM-IV diagnostic criteria,PD can be diagnosed only in the absence of medical oreurological conditions that could explain psychiatric symp-iddftrates a pore extending from the medial frontal cortex deep into the whiteatter to the level of lateral ventricles and (B) sagittal image shows theompromise of the cingulate gyrus.oms. It is worth mentioning that the patient also displayedntisocial behaviors.Under lithium carbonate (1200 mg/day) and pimozide8 mg/day) treatment there was improvement in his antiso-ial behavior. Nevertheless his impulse behavior remainednchanged as evidenced by the persistence of rage outbursts.. DiscussionThe existence of a potential neurobiological basis for BPDs suggested by possible genetic susceptibility, serotonergicysfunction, neuropsychological deficits, notably executiveysfunction and decision-making impairment, structural andunctional brain abnormalities [2,4,9].398 F.F. da Rocha et al. / Clinical Neurology andTable 1Comparison of neuropsychological performance of the patient and tenasymptomatic male controls of approximately age (from 25 through 30 yearsold) and educational level (from 6 through 8 years of formal education)Test Patient score Mean andstandarddeviation ofcontrol groupWAIS-IIIFull scale IQ (FSIQ) 90 102 ± 6.4Verbal scale IQ (VSIQ) 101 104 ± 7.1Performance scale IQ (PSIQ) 77 100 ± 6.8Perceptual organization index (POI) 89 100 ± 7.9Verbal comprehension (VCI) 105 103 ± 0.4Freedom of distractibility (FDI) 79 101 ± 7.3Working memory (WMI) 73 104 ± 8.2CPT-IIOmissions 16 2.8 ± 24Commissions 28 8.1 ± 5.2Hit reaction time 426.64 368.5 ± 62.3Rey’s complex figureCopy 20 23.5 ± 4.8Retrieval 22 21.2 ± 6.4RAVLTA1–A5 42 51.6 ± 7.4Proactive interference 0.3 0.8 ± 0.2Retroactive interference 0.7 0.8 ± 0.1Forget speed 1 0.9 ± 0.1Recognition memory 12 11.8 ± 2.7Word fluency—phonologicalF 13 13 ± 3.8A 10 9.9 ± 4.1S 12 13.7 ± 4.5Word fluency—semantic (animals) 14 18 ± 3.3F (perseverative errors) 2 0.8 ± 1.1A (perseverative errors) 1 0.7 ± 0.9S (perseverative errors) 1 0.9 ± 0.6Word fluency—semantic(animals-perseverative errors)1 1.1 ± 1.3Iowa gambling taskCD-AB (first block of 20 choices) 0 −1.2 ± 5.3CD-AB (second block of 20 choices) 0 1.5 ± 4.1CD-AB (third block of 20 choices) −2 4.3 ± 8.1ficafiwTiwcwdiaawcIpafgaaCttlicatbafwrBtdapldsmfbAs(ReferencesCD-AB (fourth block of 20 choices) −16 6.4 ± 5.9CD-AB (fifth block of 20 choices) −4 7.2 ± 6.4Cingulate cortex has been shown to subserve an array ofunctions, including emotional and attentional processing, ast is connected with amygdala, orbital and medial prefrontalortices. Conversely orbital and medial prefrontal corticesre highly interconnected with different subcortical regionsorming cortical–subcortical circuits. Based on lesion stud-es, it was suggested that structural damage to these circuitsas related with disinhibition and changes of affect [10].hese clinical features are characteristic of disruptive behav-or marked by outbursts of irritability and aggression. In lineith this, some studies have even reported that cingulateortex and adjacent regions, especially orbitofrontal cortex,hich normally exert an inhibitory influence on behavior, areysfunctional in BPD patients [2,3].Neurosurgery 110 (2008) 396–399Thus we hypothesize that some features of the personal-ty of our patient which resembles BPD, i.e. impulsivity andffect instability, could be related to cingulate cortex lesionnd secondary orbitofrontal cortex dysfunction associatedith SCHZ. Anti-social behavior presented by the patientould also be explained by an orbitofrontal dysfunction [10].nterestingly, there is a high comorbidity between anti-socialersonality disorder and BPD [11].The compromise of executive functions, decision-makingnd attention in the present case is compatible with dys-unction of different prefrontal cortex circuits. As cingulateyrus is interconnected with prefrontal cortex and it isltered in the patient, these circuits were probably secondarilyffected.The evaluation of motor and cognitive impulsiveness byPT-II (commission errors) and IGT, respectively, showedhat the patient had impaired inhibitory control and inabilityo suppress immediate reward that could lead to subsequentoss. This pattern of poor decision-making was also observedn patients of orbitofrontal lesions [6] and with several psy-hiatric disorders including BPD [9,12]. Attention deficitsre associated with prefrontal impairment, mainly when pos-erior cingulate gyrus is involved [13], and they have alsoeen related to BPD [14].Interestingly the great difference between verbal scale IQnd performance scale IQ indexes of WAIS-III is frequentlyound in BPD [5], in some psychiatric disorders presentingith executive dysfunction, such as schizophrenia [15] andight frontal pathologies [16].It is worth to mention that pharmacologic treatment ofPD remains limited and restricted to symptomatic attenua-ion. In the present case, lithium and pimozide were chosenue to the presence of significant impulsive behavior andffective instability. The poor symptomatic control in ouratient corroborates the hypothesis of prefrontal systemesion and/or dysfunction.In conclusion structural and/or functional compromise ofiscrete prefrontal and cingulate areas may lead to borderlineymptoms, mainly affective instability and impulsivity. Thisay also suggest that other borderline symptoms, such asear of abandonment and paranoia, could be related to otherrain circuits dysfunction.cknowledgementThis work was partly funded by grants from Con-elho Nacional de Desenvolvimento Cientı́fico e TecnológicoCNPq, Brazil).[1] Liang JS, Lee WT, Peng SS, Yu TW, Shen YZ. Schizencephaly: correla-tion between clinical and neuroimaging features. Acta Paediatr Taiwan2002;43:208–13.ogy and[[[[[[F.F. da Rocha et al. / Clinical Neurol[2] Berlin HA, Rolls ET, Iversen SD. Borderline personality disor-der, impulsivity, and the orbitofrontal cortex. Am J Psychiatry2005;162:2360–73.[3] Hazlett EA, New AS, Newmark R, Haznedar MM, Lo JN, Speiser LJ,et al. Reduced anterior and posterior cingulate gray matter in borderlinepersonality disorder. Biol Psychiatry 2005;58:614–23.[4] Schmahl C, Bremner JD. Neuroimaging in borderline personality dis-order. J Psychiatr Res 2006;40:419–27.[5] Wechsler D. WAIS-III: administration and scoring manual. San Anto-nio: The Psychological Corporation; 1997.[6] Conners CK. Conners’ continuous performance test manual. 2nd ed.Toronto, Canada: Multi-Health Systems; 2000.[7] Bechara A, Damasio A, Damasio H, Anderson SW. Insensitivity tofuture consequences following damage to human prefrontal cortex.Cognition 1994;50:7–12.[8] Strauss E, Sherman E, Spreen OA. Compendium of Neuropsy-chological Tests. 3rd ed. New York: Oxford University Press;2006.[9] LeGris J, van Reekum R. The neuropsychological correlates of bor-derline personality disorder and suicidal behaviour. Can J Psychiatry2006;51:131–42.[Neurosurgery 110 (2008) 396–399 39910] Bechara A, Damasio H, Damasio AR. Emotion, decision making andthe orbitofrontal cortex. Cereb Cortex 2000;10:295–307.11] Goodman G, Hull JW, Clarkin JF, Yeomans FE. Childhood antisocialbehaviors as predictors of psychotic symptoms and DSM-III-R border-line criteria among inpatients with borderline personality disorder. JPersonal Disord 1999;13:35–46.12] Bazanis E, Rogers RD, Dowson JH, Taylor P, Meux C, Staley C,et al. Neurocognitive deficits in decision-making and planning ofpatients with DSM-III-R borderline personality disorder. Psychol Med2002;32:1395–405.13] Rueckert L, Grafman J. Sustained attention deficits in patients withright frontal lesions. Neuropsychologia 1996;34:953–63.14] Posner MI, Rothbart MK, Vizueta N, Levy KN, Evans DE, ThomasKM, et al. Attentional mechanisms of borderline personality disorder.Proc Natl Acad Sci USA 2002;99:16366–70.15] Iverson GL, Woodward TS, Green P. Base rates of WAIS-R VIQ-PIQ differences in 1593 psychiatric inpatients. J Clin Psychol2001;57:1579–87.16] Boone KB, Miller BL, Lee A, Berman N, Sherman D, Stuss DT. Neu-ropsychological patterns in right versus left frontotemporal dementia.J Int Neuropsychol Soc 1999;5:616–22.

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  Previous issue date: 2008Prefrontal cortex dysfunction has been associated with a series of behavioral symptoms, such as impulsivity and affective instability, which are the defining features of several personality disorders, notably, borderline personality disorder. We report on a 27-year-old patient with schizencephaly in the right frontal lobe (cingulate cortex lesion and secondary orbitofrontal cortex dysfunction) presenting with prominent borderline features and compromise of executive functions, decision-making and attention. We hypothesize that the personality disorder of our patient could be related to cingulate cortex lesion and secondary orbitofrontal cortex dysfunction associated with schizencephaly

Teixeira, Antônio Lúcio

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Borderline personality features possibly related to cingulate and orbitofrontal cortices dysfunction due to schizencephaly.

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