A comparison of cell phenotypes in hemimegalencephaly and tuberous sclerosis

Hemimegalencephaly, an uncommon sporadic nonfamilial congenital dysplastic abnormality of the central nervous system, constitutes a pathological spect rum of neuronal migration disorders, but consistently includes abnormal lar ge neurons similar to those in the cortical tubers of tuberous sclerosis. M icroscopically, there are also cells with homogeneous and weakly eosinophil ic cytoplasm With a single eccentric nucleus, sometimes called balloon cell s (likewise prominent in tuberous sclerosis). We looked for immunohistochem ical and ultrastructural differences in the large neurons and balloon cells between hemimegalencephaly and tuberous sclerosis. Microtubule-associated protein 1B and 2, phosphorylated and nonphosphorylated neurofilament and sy naptophysin identify the large neurons and distinguish them from balloon ce lls in both entities. Balloon cells in hemimegalencephaly showed no immunor eactivity for TSC2 gene product, tuberin, and vimentin, but similar cells i n tuber tissue showed consistent immunoreactivity. Balloon cells in hemimeg alencephaly showed no immunoreactivity for glial fibrillary acidic protein, but some cells in tubers showed such immunoreactivity. Ultrastructurally, balloon cells in hemimegalencephaly contained very few lysosomes, microfila ments, and microtubules, but abundant lipofuscin granules. Similar cells in tubers had prominent lysosomes, more microfilaments and microtubules, and very few lipofuscin granules. The resemblance between abnormal cells in hem imegalencephaly and tuberous sclerosis is superficial; their immunohistoche mistry and electron microscopic profiles show distinct differences.