Pathogenic significance of neuronal migration disorders in temporal lobe epilepsy

Lee, Min-Cheol; Kim, Geun-Mo; Woo, Young Jong; Kim, Myung-Kyu; Kim, Jae-Hyoo; Nam, Sang-Chae; Suh, Jung-Jin; Chung, Woong‐Ki; Lee, Ji-Shin; Kim, Hyung-Ihl; Choi, Hwan Jun; Kim, Seung Up

doi:10.1053/hupa.2001.24997

Cited by 21 publications

(20 citation statements)

References 26 publications

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“…These epilepsies are called idiopathic, in that there is no known cause for the manifestation of epilepsy. Ongoing research in the field of medical genetics has led to the recent elucidation of an underlying cause for some of these idiopathic cases with the identification of cell migration abnormalities (Copp & Harding, 1999;Rakic, 2000;Lee et al, 2001;Haas et al, 2002;Sato et al, 2003) and numerous gene mutations in humans (Bertrand et al, 1998;Biervert et al, 1998;Wallace et al, 1998) and mouse models of epilepsy (Puranam & McNamara, 1999) that may underlie some of these idiopathic epilepsies. However, in the majority of idiopathic cases, the underlying cause of the epileptic phenotype is still not known.…”

Section: Idiopathic and Acquired Epilepsymentioning

confidence: 99%

Cellular mechanisms underlying acquired epilepsy: The calcium hypothesis of the induction and maintainance of epilepsy

DeLorenzo

Sun

Deshpande

2005

Pharmacology & Therapeutics

258

286

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Epilepsy is one of the most common neurological disorders. Although epilepsy can be idiopathic, it is estimated that up to 50% of all epilepsy cases are initiated by neurological insults and are called acquired epilepsy (AE). AE develops in 3 phases: (1) the injury (central nervous system [CNS] insult), (2) epileptogenesis (latency), and (3) the chronic epileptic (spontaneous recurrent seizure) phases. Status epilepticus (SE), stroke, and traumatic brain injury (TBI) are 3 major examples of common brain injuries that can lead to the development of AE. It is especially important to understand the molecular mechanisms that cause AE because it may lead to innovative strategies to prevent or cure this common condition. Recent studies have offered new insights into the cause of AE and indicate that injury-induced alterations in intracellular calcium concentration levels [Ca 2+ ] i and calcium homeostatic mechanisms play a role in the development and maintenance of AE. The injuries that cause AE are different, but they share a common molecular mechanism for producing brain damage -an increase in extracellular glutamate concentration that causes increased intracellular neuronal calcium, leading to neuronal injury and/or death. Neurons that survive the injury induced by glutamate and are exposed to increased [Ca 2+ ] i are the cellular substrates to develop epilepsy because dead cells do not seize. The neurons that survive injury sustain permanent long-term plasticity changes in [Ca 2+ ] i and calcium homeostatic mechanisms that are permanent and are a prominent feature of the epileptic phenotype. In the last several years, evidence has accumulated indicating that the prolonged alteration in neuronal calcium dynamics plays an important role in the induction and maintenance of the prolonged neuroplasticity changes underlying the epileptic phenotype. Understanding the role of calcium as a second messenger in the induction and maintenance of epilepsy may provide novel insights into therapeutic advances that will prevent and even cure AE.

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Section: Idiopathic and Acquired Epilepsymentioning

confidence: 99%

Cellular mechanisms underlying acquired epilepsy: The calcium hypothesis of the induction and maintainance of epilepsy

DeLorenzo

Sun

Deshpande

2005

Pharmacology & Therapeutics

258

286

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“…Previous studies have focused on primary generalized epilepsy syndromes 26 or admixed tissue from different cortical areas 25,32 or included macroscopically visible lesions besides microdysgenesis. 29,32 Hippocampal findings often were not provided 24 -26 or hippocampal sclerosis has been diagnosed in case of 25 or 30% average neuronal loss from Ammon's horn, 34,35 which does not match with the amount of neuronal loss in AHS. 1,4,36,37 Studies reporting correlations between microdysgenesis and postsurgical outcome 24,25,27 did not address outcome-relevant factors other than histopathology, for example, duration of epilepsy 38 or amount of mesial resection.…”

Section: Discussionmentioning

confidence: 95%

“…18 Unequivocal tissue signs of cortical dysplasia (CD) 29,42 were completely absent in our material, contrasting reports of 60 to 100% dual pathology (CD ϩ hippocampal sclerosis) in TLE. 34,35,43 However, severe hippocampal neuronal loss is rarely seen in lesional TLE, 36,37 and hippocampi from cases with well-defined dysplasia have not shown AHS on histopathology. 44 -46 Hippocampal alterations in dual pathology (including dysplasias) on the tissue level are very different from hippocampal sclerosis in MTLE for amount and pattern of cellular changes, 4,37,44 and therefore coexistence of CD with hippocampal sclerosis seems very rare.…”

Section: Discussionmentioning

confidence: 99%

Microdysgenesis in mesial temporal lobe epilepsy: A clinicopathological study

Kasper¹,

Stefan²,

Paulus

2003

Annals of Neurology

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The interrelationship of mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis, and febrile convulsions still remains an enigma. Additional microscopical cortical dysplasia or microdysgenesis has been suggested as pre-existent susceptibility factor rendering the affected brain vulnerable to the development of MTLE after initial precipitating injuries such as febrile convulsions. Twenty-four MTLE cases with histopathologically definite hippocampal sclerosis were examined for clearly defined features of microdysgenesis and further signs of neocortical dysplasia. Although unequivocal signs of dysplasia were absent, 29.2% of cases showed cortical neuronal clustering, 25.0% showed perivascular clustering, and 20.8% showed increased white matter neurons. The features of microdysgenesis studied here were not linked with each other and were not related to initial precipitating injuries, positive family history, or any other clinical parameter. Their suggested fundamental role as dysplastic factor within development of hippocampal sclerosis and MTLE is not confirmed.

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“…The occurrence of GCD in nearly half of all patients with MTS type 1a and MTS type 1b also point to migratory disturbances. In this respect, we observed three patients without segmental cell loss and GCD, suggesting a malformative pathomechanism to be involved [21]. Cortical dyslamination within the temporal lobe of MTS patients can often be demonstrated supporting a more extensive developmental impairment in at least a proportion of MTS cases [15, 43].…”

Section: Discussionmentioning

confidence: 99%

A new clinico-pathological classification system for mesial temporal sclerosis

et al. 2007

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We propose a histopathological classiWcation system for hippocampal cell loss in patients suVering from mesial temporal lobe epilepsies (MTLE). One hundred and seventy-eight surgically resected specimens were microscopically examined with respect to neuronal cell loss in hippocampal subWelds CA1-CA4 and dentate gyrus. Five distinct patterns were recognized within a consecutive cohort of anatomically well-preserved surgical specimens. The Wrst group comprised hippocampi with neuronal cell densities not signiWcantly diVerent from age matched autopsy controls [no mesial temporal sclerosis (no MTS); n = 34, 19%]. A classical pattern with severe cell loss in CA1 and moderate neuronal loss in all other subWelds excluding CA2 was observed in 33 cases (19%), whereas the vast majority of cases showed extensive neuronal cell loss in all hippocampal subWelds (n = 94, 53%). Due to considerable similarities of neuronal cell loss patterns and clinical histories, we designated these two groups as MTS type 1a and 1b, respectively. We further distinguished two atypical variants characterized either by severe neuronal loss restricted to sector CA1 (MTS type 2; n = 10, 6%) or to the hilar region (MTS type 3, n = 7, 4%). Correlation with clinical data pointed to an early age of initial precipitating injury 123(IPI < 3 years) as important predictor of hippocampal pathology, i.e. MTS type 1a and 1b. In MTS type 2, IPIs were documented at a later age (mean 6 years), whereas in MTS type 3 and normal appearing hippocampus (no MTS) the Wrst event appeared beyond the age of 13 and 16 years, respectively. In addition, postsurgical outcome was signiWcantly worse in atypical MTS, especially MTS type 3 with only 28% of patients having seizure relief after 1-year follow-up period, compared to successful seizure control in MTS types 1a and 1b (72 and 73%).Our classiWcation system appears suitable for stratifying the clinically heterogeneous group of MTLE patients also with respect to postsurgical outcome studies.

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Pathogenic significance of neuronal migration disorders in temporal lobe epilepsy

Cited by 21 publications

References 26 publications

Cellular mechanisms underlying acquired epilepsy: The calcium hypothesis of the induction and maintainance of epilepsy

Cellular mechanisms underlying acquired epilepsy: The calcium hypothesis of the induction and maintainance of epilepsy

Microdysgenesis in mesial temporal lobe epilepsy: A clinicopathological study

A new clinico-pathological classification system for mesial temporal sclerosis

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