Epilepsies associated with hippocampal sclerosis

Author(s)

Cendes, Fernando ^[1] ; Sakamoto, Americo C. ^[2] ; Spreafico, Roberto ^{[3, 4]} ; Bingaman, William ^[5] ; Becker, Albert J. ^[6]

Affiliation

^[1] Univ Campinas UNICAMP, FCM, Dept Neurol, BR-13083880 Campinas, SP - Brazil

^[2] Univ Sao Paulo, Ctr Epilepsy Surg CIREP, Hosp Clin Ribeirao Preto, Sao Paulo - Brazil

^[3] Ist Neurol C Besta, Epilepsy Clin, Fdn IRCCS, Milan - Italy

^[4] Ist Neurol C Besta, Epilepsy Clin, Expt Neurophysiol Unit, Milan - Italy

^[5] Cleveland Clin, Neurol Inst, Cleveland, OH 44106 - USA

^[6] Univ Bonn, Dept Neuropathol, Med Ctr, Bonn - Germany

• Document type: Review article
• Source: ACTA NEUROPATHOLOGICA; v. 128, n. 1, p. 21-37, JUL 2014.
• Web of Science Citations: 56

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. (AU)

• FAPESP's process: 13/07559-3 - BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology
• Grantee: Fernando Cendes
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC