Hypothalamic hamartomas associated with epilepsy: Ultrastructural features

John Beggs, Satoko Nakada, Kristina A. Simeone, Jie Wu, Stephen Coons, John F. Kerrigan

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Abstract

Hypothalamic hamartomas (HHs) are associated with a catastrophic form of childhood epilepsy and are intrinsically epileptogenic for the gelastic seizures that are peculiar to this disorder. The cellular mechanisms of seizure generation within HH tissue are unknown. Hypothalamic hamartoma tissue consists of well-differentiated neurons interspersed with glial cells. Based on intrinsic electrophysiologic properties, we hypothesized that small and large HH neurons would have different ultrastructural features. Surgically resected HH tissue samples from 7 patients with refractory epilepsy were studied using electron microscopy. Models of neurons were made from reconstruction of serial sections. Nissl body density, polyribosome density, glycogen density, and the ratio of nuclear area to cytoplasmic area differed significantly between small and large neurons. Abundant small neurons were found in clusters and elaborated terminals that made symmetric, putatively inhibitory, synapses. Symmetric synapses were found predominantly on the soma and proximal dendrites of large projection-like neurons, whereas asymmetric, putatively excitatory, synapses were found primarily on distal dendrites. All samples showed unusual dendritic varicosities. The presence of these morphologically and functionally distinct neurons, the large number of nerve fibers in the neuropil, and the presence of inhibitory and excitatory synapses suggest that HH tissue has the necessary substrate to generate seizures.

Original languageEnglish
Pages (from-to)657-668
Number of pages12
JournalJournal of Neuropathology and Experimental Neurology
Volume67
Issue number7
DOIs
StatePublished - Jul 2008

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All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)
  • Cellular and Molecular Neuroscience
  • Neurology

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