CASE REPORT

Schizencephaly Associated with Bipolar Affective Disorder

P. Relan, S.K. Chaturvedi, B. Shetty*

Departments of Psychiatry National Institute of Mental Health and Neurosciences and Chief Radiologist* Medinova Labs, Bangalore - 560 029, India.

Summary

Schizencephaly is a rare congenital anomaly of the brain, characterized by formation of abnormal unilateral or bilateral clefts in the cerebral hemispheres. It often manifests with partial seizures, mental retardation and hemiparesis. Only two cases of schizencephaly associated with psychosis have been reported in the literature. A patient of schizencephaly, who had bipolar affective disorder is described. It has been compared with the earlier two reported cases of schizencephaly associated with pyschosis.

Key words : Schizencephaly, Bipolar affective disorder, Neurodevelopmental anomalies.

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Introduction gray matter along the cleft, an abnormal ventricular system and other associated cerebral anomalies.6 The Schizencephaly, originally described by Wilmarth and MRI scan depicts the above findings. A key feature on later named so by Yakolev and Wadsworth, is a rare MRI is the presence of ventricular dimple, which is congenital disorder of cerebral cortical almost always seen in cases with closed lip development.1-3 It is a neuronal migration anomaly, schizencephaly. Mild hypoplasia of corpus callosum caused by insults to migrating neuroblasts during 3rd along with septo- optic dysplasia is very common.7 It to 5th gestational months. Other anomalies in this could be unilateral or bilateral, depending on the category include agyria, pachygyria, polymicrogyria, cerebral hemispheres involved. Schizencephalic cleft unilateral megalencephaly, gray matter heterotopias, occurs more often in the anterior than in posterior lissencephaly and agenesis of corpus callosum.4,5 neocortex.3 Clefts most commonly involve the Basically, schizencephaly is characterized by a cleft parasylvian region and have been divided in two traversing cerebral hemisphere, infolding of cortical subtypes. Type I have fused lips and Type II have Correspondence to : Dr. P.Relan, C/o Dr. S.K. Chaturvedi, No. separated lips. Thus, there are four categories defined 44, Type V, National Institute of Mental Health and radiologically i.e. unilateral open lip (36.2%), Neurosciences Quarters, BRC Campus, Bangalore - 560 unilateral closed lip (25.6%), bilateral open lip 029, India. 3 E-mail : [email protected] (25.6%) and bilateral closed lip (12.8%).

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Schizencephaly may occur due to various causes. It (paternal uncle’s daughter) aged 11 years, who is a may be due to localized ischemia in periventricular dwarf (almost 2 feet). Patient was well adjusted germinal matrix,8 or it may be an extreme variant of premorbidly. He was 4th of 6 sibs, born as a twin cortical dysplasia, in which the infolding of cortex along with a sister, in a hospital as full term vaginal extends all the way into the lateral ventricle.9 A report delivery, had postnatal hyperbilirubinemia, for which of schizencephaly in two affected sibs suggested he was given phototherapy for about a month and had genetic basis10 and indicated the possibility of birth weight of about 1.4 kilograms. There was no history suggestive of intrauterine exposure to any drug autosomal recessive form of transmission.11,12 or radiation or any postnatal viral infections. He Schizencephaly has recently been associated with a achieved milestones at fairly normal timings. Since germline mutation in homeobox gene EMX2 in 70% the age of 4 years he was found to have weakness of of patients.12 CMV infection, postnatally, has also left upper and lower limbs. Learning difficulties been blamed in its complex multifactorial became obvious in the 2nd year of schooling at the 13 2 pathogenesis. Intoxicants, radiation and age of about 7 years, so the family removed him from intrauterine exposure to warfarin have also been school. associated with this anomaly.14 At the age of 10 years he had an episode of mania Age at detection ranges from 8 months to 30 years. characterized by disturbed sleep and appetite, being Clinical manifestations vary from mild to severe and overtalkative, overactive, oversocial, overreligious, include developmental delay and retardation, cheerful, with occasional irritability for about 6 microcephaly, language dysfunction, focal or months. He reported delusions of grandiosity (identity generalized motor abnormalities and seizures.6 Closed and ability), occasional persecutory ideation and II lip schizencephaly usually presents with hemiparesis and III person auditory hallucinations of commanding or motor delay, whereas patients with open lip type. He was totally asymptomatic till about 3 years schizencephaly present with hydrocephalus. back when he started having similar episodes lasting 3 months and occurring every 2 months, but reached Neurodevelopmental outcome is generally poor with premorbid levels in between. Present episode had 51% showing severe deficits and 32% moderate been prolonged for more than 4 months and was impairment. However, 17% have mild or no problem. continuing even at the time of consultation. He had Closed lip schizencephaly is more likely to be been on various antipsychotics without much associated with better outcome than open lip improvement. schizencephaly (78% versus 31%). Language development is significantly more likely to be normal General physical examination showed left arm fixed in patients with unilateral schizencephaly as in midprone position and patient was unable to compared to those with bilateral clefts (48% versus perform pronation-supination movements. Radiogra- 6%). Thus, presentation and outcome vary but are phy did not show any bony abnormality. Left lower related to the extent of cortical involvement.3 limb was about 1 inch shorter than the right and he walked with a limp. Oral examination showed high Psychotic symptoms have been reported in association arched palate. Intelligence test showed IQ of 54 units with a wide array of brain abnormalities or injuries, i.e. mild mental retardation, as per ICD-10.15 but there is just a single published report on psychotic Neuropsychological assessment revealed poor symptoms in two patients with schizencephaly. In this processing in neuro-cognitive psychological motor case, another patient with schizencephaly who had areas tested. There was no evidence of scatter or bipolar affective disorder (mania with psychotic lateralization of deficits. Results of all blood tests symptoms) with mild mental retardation reported and (hemogram blood sugar and electrolytes, liver it is compared with the two cases reported earlier.1 function tests, kidney function tests, RA and ANA factors), chest radiography, ECG and EEG were Case Report within normal limits. CT scan and MRI scan showed asymmetric dilatation of right lateral ventricle. A A, 20 years male, from middle socio-economic strata, dimple was observed in the right lateral ependymal working irregularly as a furniture polisher, was surface. MRI scan also revealed deep right parietal brought with complaints of overactivity and cleft with heterotopic gray matter along with partial overtalkativeness to the psychiatry out patient clinic at hypoplasia of posterior third of body of corpus the National Institute of Mental Health and Neuro callosum. Septum and optic nerves were normal Sciences, Bangalore, India. Patient has a cousin (Fig. 1 and 2). Thus, radiological findings confirmed

195 Neurology India, 50, June 2002 Relan et al

Fig. 1 : MRI (T1WI) showing deep right parietal cleft with heterotopic gray matter and assymmetric dilatation of right Fig. 2 : MRI ( T1WI-sagittal) showing partial hypoplasia of lateral ventricle. posterior third of the body of the corpus callosum. right closed lip schizencephaly with partial hypoplasia On comparing the present patient with the earlier two of corpus callosum. The twin sister’s CT scan was reported patients there are some similarities between reported to be within normal limits and she was them.1 He had closed lip schizencephaly like one of clinically found to be maintaining well. the patients, but was unilateral. Both the cases had mental retardation and both showed moderate to good The patient was treated with Loxapine liquid (5-7mg response to treatment, which seems to keep in line hs). Later on, in view of the affective disorder, he was with the notion that closed lip schizencephaly is more prescribed carbamazepine 800 mg per day for likely to be associated with better outcome.3 The prophylaxis. He showed good improvement in 3 patient reported earlier had other problems like weeks and was maintaining near total improvement at delayed milestones, seizures, depressive symptoms, the time of discharge and had reached premorbid suicidal ideas and the eye problems, which the present levels of functioning. Follow-ups at 3 weeks, 6 weeks patient did not have. On comparing with the other and 6 months showed patient to be euthymic and reported patient, who has unilateral schizencephalic without any psychotic symptoms or behavioural cleft, we note that both these patients had the postnatal abnormalities. hyperbilirubinemia. The second patient had family history of mental illness which none of the other two Discussion had. He did not have mental retardation, however, his response to treatment was poor. All the three patients The present case has clinical manifestation of have had some motor impairment and had psychotic schizencephaly, like mental retardation and mild features characterized by auditory hallucination and motor impairment, besides the radiological evidence. delusions. The comparison does not confirm any However, this case did not have microcephaly, definite trend of common features in cases of language dysfunction or seizure. Alexander et al schizencephaly with psychosis. discussed the importance of association between schizencephaly and psychosis.1 The present case, The possible association between the bipolar affective demonstrates an association between schizencephaly disorder and schizencephaly in the present patient and bipolar affective disorder. A similar association indicate the role of neurodevelopmental abnormality was noticed by Black and Kilzieh.16 They found in the manifestation of bipolar affective disorder of schizencephaly on investigation in a patient of early onset. But we wonder whether it is just a chance psychotic bipolar depression after the patient association. Nevertheless, presence of neurodevelop- developed multiple movement disorders after getting mental anomalies may have pathoplastic effects on the imipramine. presentation of psychosis and may also influence treatment response adversely, as in the earlier cases.

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