Revisiting hippocampal sclerosis in mesial temporal lobe epilepsy according to the “two-hit” hypothesis

Hamelin, Sophie; Depaulis, Antoine

doi:10.1016/j.neurol.2015.01.560

Cited by 14 publications

(8 citation statements)

References 117 publications

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“…The focal seizures are characterized by a motionless stare and oro-alimentary automatisms (e.g., lip smacking, chewing) associated with a progressive clouding of consciousness but rarely generalized. In addition to these clinical features, the MTLE syndrome is generally associated with a hippocampal sclerosis, mainly characterized by a selective neuronal loss in the CA1/CA3 and hilus area and a proliferation of astroglial cells within the Ammon's horn of the hippocampus and the hilus of the dentate gyrus (for review see [35]).…”

Section: Mesiotemporal Lobe Epilepsy Model In Micementioning

confidence: 99%

“…Among them intrahippocampal injection of kainate in mice was shown to induce ipsilateral excitotoxic damages (i.e., cell loss in CA1, CA3 and dentate gyrus hilus) during the 2e3 weeks that follow the injection, as well as proliferation and hypertrophy of astrocytes and microglia, sprouting of the mossy fibers and dispersion and hypertrophy of neurons of the dentate gyrus [38e40]. These changes are restricted to the injected hippocampus and show a great similarity to the most severe type of hippocampal sclerosis, observed in up to 80% of mesial-temporal lobe resections from MTLE patients [35]. In this model, spontaneous seizures with a hippocampal onset occur regularly and remain stable in frequency and duration for months [39].…”

Section: Mesiotemporal Lobe Epilepsy Model In Micementioning

confidence: 99%

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Synchrotron X-ray microbeams: A promising tool for drug-resistant epilepsy treatment

Studer

Serduc

Pouyatos³

et al. 2015

Physica Medica

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Epilepsy is one of the most important neurological diseases. It concerns about 1% of the population worldwide. Despite the discovery of new molecules, one third of epileptic patients are resistant to anti-epileptic drugs and among them only a few can benefit from resective surgery. In this context, radiotherapy is an interesting alternative to the other treatments and several clinical devices exist (e.g., Gamma Knife(®)). The European Synchrotron Radiation Facility offers the possibility to develop new methods of radiosurgery and to study their antiepileptic effects. Here, we discuss several studies that we performed recently to test and try to understand the antiepileptic effects of X-ray synchrotron microbeams in different animal models of epilepsy. We showed a decrease of seizures after Interlaced Microbeam Radiotherapy (IntMRT) of the somatosensory cortex, known as the seizure generator, in a genetic model of absence epilepsy. These antiepileptic effects were stable over 4 months and with low tissular and functional side-effects. The irradiated pyramidal neurons still displayed their physiological activity but did not synchronize anymore. We also obtained a lasting suppression of seizures after IntMRT of the dorsal hippocampus in a mouse model of mesiotemporal lobe epilepsy. However, an important variability of antiepileptic efficiency was observed probably due to the small size of the targeted structure. Despite these encouraging proofs-of-concepts, there is now a need to adapt IntMRT to other models of epilepsy in rodents which are close to refractory forms of epilepsy in human patients and to implement this approach to non-human primates, before moving to clinical trials.

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Section: Mesiotemporal Lobe Epilepsy Model In Micementioning

confidence: 99%

Section: Mesiotemporal Lobe Epilepsy Model In Micementioning

confidence: 99%

Synchrotron X-ray microbeams: A promising tool for drug-resistant epilepsy treatment

Studer

Serduc

Pouyatos³

et al. 2015

Physica Medica

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“…This phenomenon of stress exacerbation is known as the dual or two‐hit hypothesis of neurodegeneration (Carvey et al, ; Leak, ). Many authors have applied the dual ‐ hit hypothesis to the hippocampus, in terms of epilectic seizure activity, schizophrenia, temporal sclerosis, memory loss, and Alzheimer's disease (McCarley et al, ; Hoffmann et al, ; Lewis, ; Somera‐Molina et al, ; Zhu et al, ; Ouardouz et al, ; Llorente et al, ; Dalton et al, ; Hill et al, ; Hamelin and Depaulis, ). However, there is no model of synergistic cell death in hippocampal neurons in response to sequential hits of proteotoxic and oxidative stressors, the two major features of neurodegenerative disorders.…”

Section: Introductionmentioning

confidence: 99%

Synergistic stress exacerbation in hippocampal neurons: Evidence favoring the dual‐hit hypothesis of neurodegeneration

et al. 2016

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The dual hit hypothesis of neurodegeneration states that severe stress sensitizes vulnerable cells to subsequent challenges so that the two hits are synergistic in their toxic effects. Although the hippocampus is vulnerable to a number of neurodegenerative disorders, there are no models of synergistic cell death in hippocampal neurons in response to combined proteotoxic and oxidative stressors, the two major characteristics of these diseases. Therefore, we developed a relatively high-throughput dual hit model of stress synergy in primary hippocampal neurons. In order to increase the rigor of our study and strengthen our interpretations, we employed three independent, unbiased viability assays at multiple timepoints. Stress synergy was elicited when hippocampal neurons were treated with the proteasome inhibitor MG132 followed by exposure to the oxidative toxicant paraquat, but only after 48h. MG132 and paraquat only elicited additive effects 24h after the final hit and even loss of heat shock protein 70 activity and glutathione did not promote stress synergy at this early timepoint. Dual hits of MG132 elicited modest glutathione loss and slightly synergistic toxic effects 48h after the second hit, but only at some concentrations and only according to two viability assays (metabolic fitness and cytoskeletal integrity). The thiol N-acetyl cysteine protected hippocampal neurons against dual MG132/MG132 hits but not dual MG132/paraquat hits. Our findings support the view that proteotoxic and oxidative stress propel and propagate each other in hippocampal neurons, leading to synergistically toxic effects, but not as the default response and only after a delay. The neuronal stress synergy observed here lies in contrast to astrocytic responses to dual hits, because astrocytes that survive severe proteotoxic stress resist additional cell loss following second hits. In conclusion, we present a new model of hippocampal vulnerability in which to test therapies, because neuroprotective treatments that are effective against severe, synergistic stress are more likely to succeed in the clinic.

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“…110 The association of mesial temporal sclerosis with prolonged febrile or intractable seizures during childhood or young adulthood suggests an acquired component, while coexisting developmental lesions such as focal cortical dysplasia in 15% of mesial temporal sclerosis cases suggests a developmental component. 110 However, it is notable that several subtypes of autoimmune encephalitis, notably anti-LGI1 encephalitis and anti-GAD encephalitis, are also strongly associated with and may potentially progress to mesial temporal sclerosis, as discussed in more detail in the above sections. malities involving the cortex with restricted diffusion (Figure 10C) and lack of mass effect (Figure 10A-D) that, when located in the limbic system, may mimic imaging findings of autoimmune limbic encephalitis.…”

Section: Seizure-related Limbic Disordersmentioning

confidence: 99%

“…Mesial temporal sclerosis predominantly affects older children and young adults. The etiology of mesial temporal sclerosis remains poorly understood and is thought to stem from developmental origin, acquired causes, or some combination of both 110 . The association of mesial temporal sclerosis with prolonged febrile or intractable seizures during childhood or young adulthood suggests an acquired component, while coexisting developmental lesions such as focal cortical dysplasia in 15% of mesial temporal sclerosis cases suggests a developmental component 110 .…”

Section: Seizure‐related Limbic Disordersmentioning

confidence: 99%

Autoimmune‐mediated encephalitis and mimics: A neuroimaging review

Liang

Chu

Kuoy

et al. 2022

Journal of Neuroimaging

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Autoimmune encephalitis is a category of autoantibody‐mediated neurological disorders that often presents a diagnostic challenge due to its variable clinical and imaging findings. The purpose of this image‐based review is to provide an overview of the major subtypes of autoimmune encephalitis and their associated autoantibodies, discuss their characteristic clinical and imaging features, and highlight several disease processes that may mimic imaging findings of autoimmune encephalitis. A literature search on autoimmune encephalitis was performed and publications from neuroradiology, neurology, and nuclear medicine literature were included. Cases from our institutional database that best exemplify major imaging features were presented.

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Revisiting hippocampal sclerosis in mesial temporal lobe epilepsy according to the “two-hit” hypothesis

Cited by 14 publications

References 117 publications

Synchrotron X-ray microbeams: A promising tool for drug-resistant epilepsy treatment

Synchrotron X-ray microbeams: A promising tool for drug-resistant epilepsy treatment

Synergistic stress exacerbation in hippocampal neurons: Evidence favoring the dual‐hit hypothesis of neurodegeneration

Autoimmune‐mediated encephalitis and mimics: A neuroimaging review

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