Focal cortical dysplasia type II B

Type IIB focal cortical dysplasia (FCD) is an important cause of drug resistant epilepsy.

Sixteen FCD IIB cases were retrieved along with 16 Focal cortical dysplasia type II A (FCD IIA) cases for comparison. Immunohistochemistry was performed for tuberin, hamartin, mTOR pathway markers, markers of stem cell phenotype, and Wnt pathway markers. Mutation analysis for TSC1 and TSC2 was performed by sequencing in 9 FCD cases.

All FCD cases showed preserved hamartin and tuberin immunoreactivity. Aberrant immunoreactivity of phospho-P70S6 kinase, S6 ribosomal, phospho-S6 ribosomal and Stat3 was noted in FCD IIB, with variable phospho-4E-BP1 (45%) and absent phospho-Stat3 expression. Immunoreactivity for phospho-P70S6 kinase (100%), S6 ribosomal protein (100%) and Stat3 (100%) was noted in FCD IIA, but not for phospho-S6 ribosomal, phospho-4E-BP1 and phospho-Stat3. c-Myc immunoreactivity was noted in all FCD cases. Nestin (81%) and Sox 2 (88%) stained balloon cells in FCD IIB (44%), while in FCD IIA cases were negative. All FCD cases were immunopositive for Wnt, but were negative for β-Catenin and cyclin-D1. TSC mutations were detected in two cases of FCD IIB.

Abnormal mTOR pathway activation exists in FCD IIB and IIA, however, it shows differential immunoreactivity profile, indicating varying degrees of dysregulation. Labeling of neuronal stem cell markers in balloon cells suggests they are phenotypically immature. TSC1/2 mutation play a role in the pathogenesis of FCD. Deep targeted sequencing is preferred diagnostic technique since conventional sanger sequencing often fails to detect low-allele frequency variants involved in mTOR/TSC pathway genes, commonly found in FCD 1).

However, Balloon cells located in the medial temporal lobe have been seldom reported. Mao et al. aimed to discussed the clinical and pathological features of Type IIB FCD with balloon cells in the medial temporal lobe (MTLE-FCDIIB) and the differential diagnosis with other types of mesial temporal lobe epilepsy.

Three MTLE-FCDIIB cases were enrolled from Peking Union Medical College Hospital. Clinical and neuroimaging data were analyzed and histology features observed on hematoxylin-eosin (H&E) staining and immunochemical staining, including vimentin, nestin, S-100, CD34, neuronal nuclei antigen (Neun), glial fibrillary acidic protein (GFAP), neurofilament heavy chain (SMI32), were discussed.

All cases involved drug-resistant epilepsy patients with childhood onset. The semiology of the epileptic seizure was a highly frequent partial seizure with or without generalized tonic-clonic seizures. Magnetic resonance imaging showed hyper-intensity in the medial temporal lobe without atrophy, different from mesial temporal sclerosis. Histological examination indicated the presence of balloon cells in the white matter of the para-hippocampal gyrus, subiculum, and cornu ammonis with cortical disorganization, and SMI32 positive dysmorphic neurons in the gray matter. Balloon cells were immunohistochemically stained with vimentin and nestin. Granular cell dispersion and pyramidal cell loss were not found.

The presence of balloon cells in the medial temporal lobe is observed in a rare subgroup of FCD, named MTLE-FCDIIB. It has distinct clinical manifestations, neuroimaging features, pathological changes, and prognosis, which should be differentiated from mesial temporal lobe sclerosis and mesial temporal lobe tumors. Our findings enable more accurate diagnosis of mesial temporal lobe epilepsy 2).

A homogeneous population of five patients with type IIb FCD was evaluated. Focal cortical thickening and cortical ribbon hyper-intensity, blurring of the grey-white matter junction and hyper-intensity of the subcortical white matter on T2-weighted/FLAIR images were present in all patients. Cortical features had a complete concordance between intraoperative ultrasound (ioUS) and MRI. In particular ioUS thickening and hyper-echogenicity of cortical ribbon were identified in all cases (100%). Contrary, hyper-echoic subcortical white matter was detected in 60% of the patients. IoUS images resulted in clearer lesion borders than MRI images.

The study confirms the potentials of ioUS as a valuable diagnostic tool to guide FCD surgeries 3).

Kumari K, Sharma MC, Kakkar A, Malgulwar PB, Pathak P, Suri V, Sarkar C, Chandra SP, Faruq M. mTOR pathway activation in focal cortical dysplasia. Ann Diagn Pathol. 2020 Apr 10;46:151523. doi: 10.1016/j.anndiagpath.2020.151523. [Epub ahead of print] PubMed PMID: 32325422.
Mao C, Jin L, Dou W, Lu Q, Zhou L, Ren H, Zhao Y, Feng F, Guo Y, Gao J. Type IIB focal cortical dysplasia with balloon cells in medial temporal lobe epilepsy: Clinical, neuroimaging, and histopathological findings. Epilepsy Res. 2019 Aug 13;157:106189. doi: 10.1016/j.eplepsyres.2019.106189. [Epub ahead of print] PubMed PMID: 31472401.
Prada F, Gennari AG, Del Bene M, Bono BC, Quaia E, D'Incerti L, Villani F, Didato G, Tringali G, DiMeco F. Intraoperative ultrasonography (ioUS) characteristics of focal cortical dysplasia (FCD) type II b. Seizure. 2019 Mar 12;69:80-86. doi: 10.1016/j.seizure.2019.02.020. [Epub ahead of print] PubMed PMID: 30999253.
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