PMC4271583_01
PMC4271583_02
Electroencephalogram recording on day 25. The EEG shows a non-synchronized pattern with suppressions, multifocal sharp waves, and a focal epileptic seizure in the left hemisphere.
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F1
At day 25, the EEG pattern was characterized by sharp waves and focal seizures isolated on the left hemisphere (Figure 1).
MRI findings on day 7. (A) T1-weighted MRI (inversion recovery) shows discrete swelling of the basal nuclei and thalamus. (B) T2-weighted MRI shows a decreased signal in basal nuclei and thalamus.
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Magnetic resonance imaging (MRI; Siemens Sonata 1.5 T, Erlangen, Germany) at day 7 showed discrete swelling and hyperintensity of the basal nuclei (T1-weighted imaging; Figure 2).
Histopathology of the frontal cortex shows mild malformation of cortical development. (A) H&E staining at low magnification shows a normal six-layered architecture of the cortex. (B) At high magnification of the cortex and cortical boundary, heterotopic neurons displaced to the white matter make it difficult to distinguish between the gray and white matter border (H&E). (C) In the frontal cortex of a control subject, the gray-white matter junction appears sharply demarcated (H&E). (D) Abnormal clusters of SMI31-immunoreactive neurons (arrow) are visible in the deep cortical layers. (E,F) The deep white matter (>500 mm from the cortical border) shows increased cellularity by heterotopic neurons [(E), stain against the microtubule associated protein 2 (MAP2); (F) stain against extranuclear RNA identifying neurons]. (G) The heterotopic neurons in the deep white matter, identified by their MAP2-immunoreactivity, have normal morphology and immunophenotype. (H) The deep white matter harboring the heterotopic neurons is gliotic with numerous vimentin-positive reactive astrocytes. (A) 25x; (B,C,E,F) 100x; (D,G,H) 200x.
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Microscopic examination of the cerebral cortex showed a six-layered architecture without obvious dyslamination or columnar disorganization (Figure 3A) (see additional materials for details). Occasional neuronal clustering in cortical layers V and VI was observed in the frontal lobes (Figure 3D). The interface between cortex and underlying white matter was diffusely blurred by the presence of heterotopic neurons displaced to the white matter, as compared to normal (Figures 3B,C). Numerous individual neurons were also found in deep white matter locations (mean 47 MAP2+ neurons/mm2; mean 6 MAP + neurons/mm2 in the age-matched control) (Figures 3E,F). These heterotopic neurons had normal morphology and immunophenotypic profile (Figure 3G). The cortex and underlying white matter displayed intense reactive gliosis (Figure 3H).