Epileptogenic but MRI-normal perituberal tissue in Tuberous Sclerosis Complex contains tuber-specific abnormalities

Alexander A. Sosunov, Robert A. McGovern, Charles B. Mikell, Xiaoping Wu, David G. Coughlin, Peter B. Crino, Howard L. Weiner, Saadi Ghatan, James E. Goldman, Guy M. McKhann

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

INTRODUCTION: Recent evidence has implicated perituberal, MRI-normal brain tissue as a possible source of seizures in tuberous sclerosis complex (TSC). Data on aberrant structural features in this area that may predispose to the initiation or progression of seizures are very limited. We used immunohistochemistry and confocal microscopy to compare epileptogenic, perituberal, MRI-normal tissue with cortical tubers.

RESULTS: In every sample of epileptogenic, perituberal tissue, we found many abnormal cell types, including giant cells and cytomegalic neurons. The majority of giant cells were surrounded by morphologically abnormal astrocytes with long processes typical of interlaminar astrocytes. Perituberal giant cells and astrocytes together formed characteristic "microtubers". A parallel analysis of tubers showed that many contained astrocytes with features of both protoplasmic and gliotic cells.

CONCLUSIONS: Microtubers represent a novel pathognomonic finding in TSC and may represent an elementary unit of cortical tubers. Microtubers and cytomegalic neurons in perituberal parenchyma may serve as the source of seizures in TSC and provide potential targets for therapeutic and surgical interventions in TSC.

Original languageEnglish (US)
Pages (from-to)17
Number of pages1
JournalActa Neuropathologica Communications
Volume3
DOIs
StatePublished - Apr 2 2015
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank Peter Canoll, Marisa Cotrina, Markel Olabarria-Larizgoita, and Eileen Guifoyle for discussions, valuable comments and suggestions. This research was supported by National Institutes of Health Grant NS42803 and by the Tuberous Sclerosis Alliance TSC Innovator Award.

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