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ObjectiveTo better evaluate the imaging spectrum of subcortical heterotopic gray matter brain malformations (subcortical heterotopia [SUBH]), we systematically reviewed neuroimaging and clinical data of 107 affected individuals.MethodsSUBH is defined as heterotopic gray matter, located within the white matter between the cortex and lateral ventricles. Four large brain malformation databases were searched for individuals with these malformations; data on imaging, clinical outcomes, and results of molecular testing were systematically reviewed and integrated with all previously published subtypes to create a single classification system.ResultsReview of the databases revealed 107 patients with SUBH, the large majority scanned during childhood (84%), including more than half before 4 years (59%). Although most individuals had cognitive or motor disability, 19% had normal development. Epilepsy was documented in 69%. Additional brain malformations were common and included abnormalities of the corpus callosum (65/102 [64%]), and, often, brainstem or cerebellum (47/106 [44%]). Extent of the heterotopic gray matter brain malformations (unilateral or bilateral) did not influence the presence or age at onset of seizures. Although genetic testing was not systematically performed in this group, the sporadic occurrence and frequent asymmetry suggests either postzygotic mutations or prenatal disruptive events. Several rare, bilateral forms are caused by mutations in genes associated with cell proliferation and polarity (EML1, TUBB, KATNB1, CENPJ, GPSM2).ConclusionThis study reveals a broad clinical and imaging spectrum of heterotopic malformations and provides a framework for their classification.

ObjectiveTo describe a homogeneous subtype of periventricular nodular heterotopia (PNH) as part of a newly defined malformation complex.MethodsObservational study including review of brain MRI and clinical findings of a cohort of 50 patients with PNH in the temporo-occipital horns and trigones, mutation analysis of the FLNA gene, and anatomopathologic study of a fetal brain.ResultsThere were 28 females and 22 males. All were sporadic with the exception of an affected mother and son. Epilepsy occurred in 62%, cerebellar signs in 56%, cognitive impairment in 56%, and autism in 12%. Seventy percent were referred within the 3rd year of life. Imaging revealed a normal cerebral cortex in 76% and abnormal cortical folding in 24%. In all patients the hippocampi were under-rotated and in 10% they merged with the heterotopia. Cerebellar dysgenesis was observed in 84% and a hypoplastic corpus callosum in 60%. There was no gender bias or uneven gender distribution of clinical and anatomic severity. No mutations of FLNA occurred in 33 individuals examined. Heterotopia in the fetal brain revealed cytoarchitectonic characteristics similar to those associated with FLNA mutations; cortical pathology was not typical of polymicrogyria. Cerebellar involvement was more severe and the hippocampi appeared simple and under-rotated.ConclusionsThis series delineates a malformation complex in which PNH in the trigones and occipito-temporal horns is associated with hippocampal, corpus callosum, and cerebellar dysgenesis. This subtype of PNH is distinct from classic PNH caused by FLNA mutations.

Epidermal nevus syndrome is a neurocutaneous disorder that involves both multiple epidermal nevi and congenital abnormalities of some organs, including the brain. Although the clinical syndrome might superficially resemble some inherited disorders, epidermal nevus syndrome seems to be sporadic rather than familial. Brain abnormalities such as hemimegalencephaly, in which one side of the brain is excessively large, are common in cases of epidermal nevus syndrome. Neurologic symptoms resembling those of hemorrhage or infarction (tissue damage due to inadequate oxygen) are also common. The authors present the case of one patient with epidermal nevus syndrome with evidence of infarction, and review three more cases from the medical literature. The patient was noted to develop decreased use of the left arm at three months of age, and at nine months a spastic hemiparesis developed. Computed tomography revealed an infarction in the region of the right middle cerebral artery, and some associated atrophy. The patient recovered, and at three years is developing well. He did show some mild speech delay. It was not possible to identify any blood vessel abnormalities in this child. However, in the three cases reported in the medical literature, an occluded artery, an aneurysm, and an angioma could be identified. The authors suggest that when stroke-like symptoms are observed in a patient with epidermal nevus syndrome, they probably indicate a stroke. The occurrence of such events in patients with epidermal nevus syndrome most likely represents a predilection of these patients to have vascular abnormalities. (Consumer Summary produced by Reliance Medical Information, Inc.)