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Epilepsies associated with hippocampal sclerosis

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Abstract

Hippocampal sclerosis (HS) is considered the most frequent neuropathological finding in patients with mesial temporal lobe epilepsy (MTLE). Hippocampal specimens of pharmacoresistant MTLE patients that underwent epilepsy surgery for seizure control reveal the characteristic pattern of segmental neuronal cell loss and concomitant astrogliosis. However, classification issues of hippocampal lesion patterns have been a matter of intense debate. International consensus classification has only recently provided significant progress for comparisons of neurosurgical and clinic-pathological series between different centers. The respective four-tiered classification system of the International League Against Epilepsy subdivides HS into three types and includes a term of “gliosis only, no-HS”. Future studies will be necessary to investigate whether each of these subtypes of HS may be related to different etiological factors or with postoperative memory and seizure outcome. Molecular studies have provided potential deeper insights into the pathogenesis of HS and MTLE on the basis of epilepsy-surgical hippocampal specimens and corresponding animal models. These include channelopathies, activation of NMDA receptors, and other conditions related to Ca2+ influx into neurons, the imbalance of Ca2+—binding proteins, acquired channelopathies that increase neuronal excitability, paraneoplastic and non-paraneoplastic inflammatory events, and epigenetic regulation promoting or facilitating hippocampal epileptogenesis. Genetic predisposition for HS is clearly suggested by the high incidence of family history in patients with HS, and by familial MTLE with HS. So far, it is clear that HS is multifactorial and there is no individual pathogenic factor either necessary or sufficient to generate this intriguing histopathological condition. The obvious variety of pathogenetic combinations underlying HS may explain the multitude of clinical presentations, different responses to clinical and surgical treatment. We believe that the stratification of neuropathological patterns can help to characterize specific clinic-pathological entities and predict the postsurgical seizure control in an improved fashion.

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Acknowledgments

FC’s work is supported by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil), Grant # 2013/07559-3. AJB’s work is supported by EuroEpinomics and DFG (SFB 1089, KFO 177), European Union EpiTarget Consortium in FP7, the Else Kröner-Fresenius and German Israeli Foundations and BonFor. RS is supported by the Italian Ministry of Health and Associazione “P: Zorzi” per le Neuroscienze.

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Authors and Affiliations

  1. Department of Neurology, FCM, University of Campinas-UNICAMP, Campinas, SP, 13083-880, Brazil

    Fernando Cendes

  2. Center for Epilepsy Surgery (CIREP), Hospital das Clínicas de Ribeirão Preto, University of São Paulo, São Paulo, Brazil

    Americo C. Sakamoto

  3. Epilepsy Clinic and Experimental Neurophysiology Unit, Fondazione IRCCS, Istituto Neurologico “C. Besta”, Milan, Italy

    Roberto Spreafico

  4. Neurologic Institute Cleveland Clinic, Cleveland, USA

    William Bingaman

  5. Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany

    Albert J. Becker

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  1. Fernando Cendes
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  2. Americo C. Sakamoto
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  3. Roberto Spreafico
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  4. William Bingaman
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  5. Albert J. Becker
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Correspondence to Fernando Cendes.

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Cendes, F., Sakamoto, A.C., Spreafico, R. et al. Epilepsies associated with hippocampal sclerosis. Acta Neuropathol 128, 21–37 (2014). https://doi.org/10.1007/s00401-014-1292-0

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