Dysplastic cortical formation in a patient with schizophrenia.

Sir,

A considerable body of evidence from neuropathological studies and neuroimaging studies of brain structure has supported that schizophrenia should be regarded as a long-term consequence of abnormal or dysplastic brain development.[1] However, efforts at “localization” of the underlying pathophysiology of schizophrenia to special locations in the frontal cortex have not been successful, which has led researchers to believe schizophrenia is a dysfunctional integration rather than a functional segregation involving localized pathology.[2] Here, we report a case of undifferentiated schizophrenia with cortical dysplasia to contribute to the growing body of literature in neurodevelopmental hypothesis of schizophrenia.[1]

Ms D, a 27-year-old single female, presented in April 2007 with symptoms of social withdrawal, anhedonia, and suspiciousness of 5 years duration, followed by 1½ years duration of delusions of persecution and reference, asociality, avolition, poor personal care, and impaired vegetative functions. There was no contributory past or family history, and she had personal history of full-term forceps delivery. General physical and systemic examination was within normal limits, and no minor physical anomalies were detected. She had failed adequate trials of Olanzapine and Risperidone. She was hospitalized for evaluation and her all baseline investigations were within normal limits. Her IQ was 84 on Binne Kamat test. Neuropsychological testing revealed mild deficits in inferior temporal lobe functioning. Magnetic resonance imaging (MRI) done in May 2007 revealed ill-defined margins of the cingulate gyrus. A possibility of cortical dysplasia was considered. She was started on Amisulpiride 600 mg and Escitalopram 20 mg and was discharged after 25 days.

She was readmitted in March 2008. There was no improvement with adequate trials of Amisulpiride. Repeat MRI showed hypointense lesion involving grey matter of anterior portion of left frontal lobe in the parafalcine region on T1 images [Figure 1], which turned hyperintense on T2 and FLAIR images. MR spectroscopy showed minimal elevation of choline. Cortical dysplasia versus low-grade neoplasm was considered. She was then started on Clozapine as she had failed three adequate trials of antipsychotics. She did not show improvement during the 30 days of hospital stay. The patient has not come for follow-up subsequently.

Figure 1

T1 image showing hypointense lesion involving grey matter of anterior portion of left frontal lobe in the para falcine region, suggestive of cortical dysplasia

There are cases reporting that anatomical dysconnectivity (between frontal and temporal cortex) in schizophrenia may be caused by dysplasia.[3] In favor of the hypothesis that the primary damage in schizophrenia is actually located in the frontal lobes, Goldberg,[4] points to the frontal lobes’ unique role as an integrator of many different functions. On the basis of neuroanatomical considerations alone, the prefrontal cortex has more extensive, direct, and reciprocal connections with the implicated neural structures than any other brain area.[5] Different lesion sites within this network or variations in the degree of damage may be responsible for different clinical subtypes, consistent with the clinical heterogeneity of the disorder.

The highlight of our report is the focal lesion in left frontal lobe, suggestive of dysplastic cortical formation and an absence of conspicuous gliotic reaction. Also, the later risk may be increased by cerebral hypoxia as a complication of birth which was assisted by forceps.