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From the Department of Clinical and Experimental Epilepsy, Divisions of Neuropathology (M.T., L.M.) and Clinical Neurology (C.C., M.Y., M.J.K., L.C., S.M.S.), Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London; and National Society for Epilepsy (C.C., M.Y., M.J.K., S.M.S.), Bucks, UK.
Address correspondence and reprint requests to Dr. Maria Thom, Division of Neuropathology, Institute of Neurology, Queen Square, London, WC1N 3BG, UK M.Thom{at}ion.ucl.ac.uk
Background: Hippocampal sclerosis (HS) is the most common surgical pathology associated with mesial temporal lobe epilepsy (MTLE). HS is typically characterized by mossy fiber sprouting (MFS) and reorganization of neuropeptide Y (NPY) fiber networks in the dentate gyrus. One potential cause of postoperative seizure recurrence following temporal lobe surgery may be the presence of seizure-associated bilateral hippocampal damage. We aimed to investigate patterns of hippocampal abnormalities in a postmortem series as identified by NPY and dynorphin immunohistochemistry.
Methods: Analysis of dentate gyrus fiber reorganization, using dynorphin (to demonstrate MFS) and NPY immunohistochemistry, was carried out in a postmortem epilepsy series of 25 cases (age range 21–96 years). In 9 patients, previously refractory seizures had become well controlled for up to 34 years prior to death.
Results: Bilateral MFS or abnormal NPY patterns were seen in 15 patients including those with bilateral symmetric, asymmetric, and unilateral HS by conventional histologic criteria. MFS and NPY reorganization was present in all classical HS cases, more variably in atypical HS, present in both MTLE and non-MTLE syndromes and with seizure histories of up to 92 years, despite seizure remission in some patients.
Conclusion: Synaptic reorganization in the dentate gyrus may be a bilateral, persistent process in epilepsy. It is unlikely to be sufficient to generate seizures and more likely to represent a seizure-induced phenomenon.
Abbreviations: AED = antiepileptic drug; CA1p = CA1-predominant hippocampal sclerosis; CHS = classical hippocampal sclerosis; EFG = end folium gliosis; EFS = end folium sclerosis; GCD = granule cell dispersion; GCL = granule cell layer; HS = hippocampal sclerosis; MFS = mossy fiber sprouting; MTLE = mesial temporal lobe epilepsy; NPY = neuropeptide Y; ROI = region of interest; SE = status epilepticus; TLE = temporal lobe epilepsy.
Supplemental data at www.neurology.org
Editorial, page 1008
e-Pub ahead of print on August 26, 2009, at www.neurology.org.
Supported by MRC grant G79059. This work was undertaken at UCLH/UCL, which received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centres funding scheme.
Disclosure: Author disclosures are provided at the end of the article.
Received July 19, 2008. Accepted in final form July 6, 2009.
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Neurology 2009 73: 1008-1009.
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  M. Madden and T. Sutula Beyond hippocampal sclerosis: The rewired hippocampus in temporal lobe epilepsy Neurology, September 29, 2009; 73(13): 1008 - 1009. [Full Text] [PDF]
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