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A proposed mechanism of seizure generation in the temporal lobe of patients with MS. A Type I GML together with the associated underlying white matter lesion, evidenced by and in part due to the presence of activated microglia, produce neuronal dysfunction (mitochondrial stress) and cell death (interneuron loss within layer VI). Resulting damage to projecting neurons contributes to the loss of interneurons in layer IV. The resulting loss of inhibition enhances the risk of seizures. Additional stressors including concurrent infection are then more likely to result in the emergence of seizures. MS: multiple sclerosis; GML: grey matter lesion.
Source publication
Seizures are recognised in multiple sclerosis (MS), but their true incidence and the mechanism by which they are associated with MS is unclear.
The objective of this paper is to determine the lifetime frequency of seizures in the United Kingdom MS Tissue Bank (UKMSTB) population and any pathological features associated with seizures.
We evaluated 2...
Citations
... A common cause of seizure is fevers (12). Other causes include head trauma, stroke or lack of oxygen to the brain, genetic defects or brain tumors, hypoglycemia and deficiency of vitamin B6 (13)(14)(15)(16) With the epidemiological studies in the field of children's seizure disorder, the incidence, prevalence, genetic background, age, and therapeutic approaches can be evaluated (17). ...
Introduction: Seizure in children with the prevalence of 4 to 6 cases in 1000 is the most common neurological disorder in pediatrics. This study aimed to determine the causes of seizures in children admitted to Kerman hospitals in 2017
Materials and methods: In this retrospective study, 250 hospitalized children suffering from seizure were selected through census method. Data collection tool was a checklist. The obtained data was analyzed employing SPSS24 software, using chi-square, and correlation coefficient statistical tests at the significant level P < 0.05.
Results: Out of 250 children studied, 55.6% were male and 44.4% were female. The mean age of the children was 10.54 + 3.7 years. 80.4% were born with vaginal delivery and 19.6% were born with cesarean section. 44% of the patients had febrile seizure, 23.2% epilepsy, 12.4% infection, 10% gastroenteritis, 5.2% static encephalopathy, 2.8% meningitis, 1.6% hypocalcaemia, 0.4 % metabolic disorders and 0.4 % tumor. That underlying factors of febrile seizure were upper respiratory infection (43.6%), gastroenteritis (15.7%), shigellosis (10.5%), urinary infection (9.9%), pneumonia (8.1%), unidentified fever (7.8%), otitis (3%) and dental abscess (1.4%) respectively.
Conclusion: According to this study, the most common cause of the seizure is a febrile seizure, which confirms the results of other studies. Common seizure require diagnosis, planning, and special treatments that can be obtained by taking a complete history, accurate examination, and effective Para clinical evaluations.
Keywords: Seizure, Children, Etiology
... По данным I. Dagiasi и соавт., только 46% пациентов не имели приступов на фоне лечения противоэпилептическими препаратами [11]. Наличие эпилептических приступов у больных РС чаще приводят к более значительному снижению когнитивных функций [12], более высокой частоте обострений, быстрому нарастанию показателя EDSS, ранней утрате способности к передвижению и летальным исходам [13,14]. Предполагается, что одной из возможных причин отсутствия купирования эпилептических приступов у больных РС является то, что цель достижения ремиссии эпилепсии не преследуется столь же энергично при наличии другого неврологического расстройства [11]. ...
Clinical case of structural epilepsy in a patient with multiple sclerosis is presented, which shows the achievement of seizure’s stable remission, which is extremely rare in forms of epilepsy with a multi-focal lesion another etiology and a long history of the disease without combination with multiple sclerosis. Video-EEG monitoring, positron emission tomography of the brain with ¹⁸ F-deoxyglucose, expand the possibilities of diagnosing form of epilepsy in patients with combined pathology, which allows prescribing adequate therapy.
... Acute seizures and epilepsy were also reported in other neuroinflammatory disorders of the central nervous system, e.g., in myelin oligodendrocyte glycoprotein antibody disease, acute disseminated encephalomyelitis or neuromyelitis optica spectrum disorder. A few available neuroimaging and neuropathological studies suggested that the extent of cortical grey matter damage is proportional to the risk of epilepsy occurrence in patients with MS (Calabrese et al., 2012;Nicholas et al., 2016). However, despite the significant progress achieved in elucidating the molecular and cellular basis of MS pathology, mechanisms of increased susceptibility to seizure generation in acute and chronic neuroinflammation are poorly understood, thereby, leaving many questions open. ...
... Overall, inflammatory lesions, neuronal cell loss, and axonal demyelination were proposed as driving mechanisms (or "culprit mechanisms") of cortical hyperexcitability and epilepsy occurrence in MS (Nicholas et al., 2016). Upon neuroinflammation, a range of pathological phenomena, such as bloodbrain barrier disruption, immune cell infiltration, overexpression of pro-inflammatory cytokines and chemokines, and glial cell dysfunction disturb the homeostatic environment of neurons ( Figure 1B). ...
... Inhibitory neuronal cell loss (as an indicator of reduced inhibitory drive) is a critical prerequisite for MS-induced epileptogenesis. Selective loss of GABA-ergic inhibitory interneurons is evidenced in cortical layers IV and VI of the temporal lobe in patients with MS and concomitant epilepsy (Nicholas et al., 2016). Focal loss of inhibitory interneurons was related to type I cortical lesions (also known as leukocortical lesions), which could be the source of inflammatory cells responsible for neuronal injury (Nicholas et al., 2016). ...
... Imaging studies have indicated the involvement of the MTG in cognitive functions like language, semantic memory processing and multimodal sensory integration, with the posterior MTG mainly linked to language processing (Onitsuka et al., 2004;Xu et al., 2015). Clinically, MS patients diagnosed with seizures have been found to have grey matter lesions in the MTG and reduced neuronal number in histopathology of this region (Nicholas et al., 2016). Since an increase in seizures is hypothesized to stem from neuronal dysfunction or damage, it could be implied that the variation in RSFC was also a result of such damage. ...
Background:
Multivoxel pattern analysis (MVPA) has emerged as a powerful unbiased approach for generating seed regions of interest (ROIs) in resting-state functional connectivity (RSFC) analysis in a data-driven manner. Studies exploring RSFC in multiple sclerosis have produced diverse and often incongruent results.
Objectives:
The aim of the present study was to investigate RSFC differences between persons with relapsing-remitting multiple sclerosis (RRMS) and healthy controls (HC).
Methods:
We performed a whole-brain connectome-wide MVPA in 50 RRMS patients with expanded disability status scale ≤4 and 50 age and gender-matched HC.
Results:
Significant group differences were noted in RSFC in three clusters distributed in the following regions; anterior cingulate gyrus, right middle frontal gyrus and frontal medial cortex. Whole-brain seed-to-voxel RSFC characterization of these clusters as seed ROIs revealed network specific abnormalities, specifically in the anterior cingulate cortex and the default mode network.
Conclusions:
The network-wide RSFC abnormalities we report study agree with previous findings in RRMS. The cognitive and clinical implications of these are discussed herein.
... There were reports that patients with MS with systemic infections were more likely to develop seizures, although the role of infectious agents in the development of seizures/epilepsy remains unknown. 50,51 Rather, the high responsiveness of acute symptomatic seizures to immunotherapy in MS indicates a predominant role of both demyelination and inflammation in the development of acute seizures in MS. 13 Demyelination may lead to loss of function of the inwardly rectifying potassium (K + ) channels (Kir4.1), Na + -K + -ATPase, and certain connexins, resulting in an elevation of extracellular K + concentration and thus an increase in neuronal excitability. ...
... 51 Both mechanisms collectively contribute to changes including gliosis, synaptic dysfunction, and selective neuronal loss, especially of inhibitory interneurons. 50 Those degenerative changes of corticosubcortical structures in MS patients further lead to reorganization of synaptic circuitry and aberrant brain networks responsible for the epileptogenesis process. 31,50,55 MS does not contribute to neuronal pathology directly. ...
... Concomitant systemic infections in MS patients may decrease the seizure threshold. 50 MS patients with seizures also had an earlier disease onset than those without. 4 The annualized relapse rate of MS was also higher in MS with seizures. ...
Seizure is one of the manifestations of central nervous system inflammatory demyelinating diseases, which mainly include multiple sclerosis (MS), aquaporin 4 antibody‐positive neuromyelitis optica spectrum disorder (AQP4‐NMOSD), and myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD). Acute symptomatic seizures secondary to MS/AQP4‐NMOSD/MOGAD occur in the acute phase of the diseases, and are more frequent in MOGAD. In contrast, recurrent nonprovoked seizures, mainly attributed to autoimmune‐associated epilepsy, occur in the nonacute phase of the diseases. Seizures in MS/AQP4‐NMOSD/MOGAD mostly have a focal onset. MS patients with concomitant systemic infections, earlier onset, and greater disease activity are more likely to have seizures, whereas factors such as greater MS severity, the presence of status epilepticus, and cortical damage indicate a greater risk of developing epilepsy. In MOGAD, cerebral cortical encephalitis and acute disseminated encephalomyelitis (ADEM)‐like phenotypes (predominately ADEM and multiphasic disseminated encephalomyelitis) indicate a greater seizure risk. Multiple relapses with ADEM‐like phenotypes predict epilepsy in pediatrics with MOGAD. Pathophysiologically, acute symptomatic seizures in MS are associated with neuronal hyperexcitability secondary to inflammation and demyelination. Chronic epilepsy in MS is largely due to gliosis, neuronal dysfunction, and synaptic abnormalities. The mainstay of treatment for seizures secondary to MS/AQP4‐NMOSD/MOGAD consists of immunotherapy along with antiseizure medications. This critical review discusses the most‐updated evidence on epidemiology, clinical correlates, and inflammatory mechanisms underlying seizures and epilepsy in MS/AQP4‐NMOSD/MOGAD. Treatment cautions including drug‐drug interactions and the impact of treatments on the diseases are outlined. We also highlight pitfalls and challenges in managing such patients and future research perspectives to address unsolved questions.
... Imaging studies have indicated the involvement of the MTG in cognitive functions like language, semantic memory processing and multimodal sensory integration, with the posterior MTG mainly linked to language processing (Onitsuka et al., 2004;Xu et al., 2015). Clinically, MS patients diagnosed with seizures have been found to have grey matter lesions in the MTG and reduced neuronal number in histopathology of this region (Nicholas et al., 2016). Since an increase in seizures is hypothesized to stem from neuronal dysfunction or damage, it could be implied that the variation in RSFC was also a result of such damage. ...
Background
Multivoxel pattern analysis (MVPA) has emerged as a powerful unbiased approach for generating seed regions of interest (ROIs) in resting-state functional connectivity (RSFC) analysis in a data-driven manner. Studies exploring RSFC in multiple sclerosis have produced diverse and often incongruent results.
Objectives
The aim of the present study was to investigate RSFC differences between persons with relapsing-remitting multiple sclerosis (RRMS) and healthy controls (HC).
Methods
We performed a whole-brain connectome-wide MVPA in 50 RRMS patients with expanded disability status scale ≤4 and 50 age and gender-matched HCs.
Results
Significant group differences were noted in RSFC in three clusters distributed in the following regions; anterior cingulate gyrus, right middle frontal gyrus, and frontal medial cortex. Whole-brain seed-to-voxel RSFC characterization of these clusters as seed ROIs revealed network-specific abnormalities, specifically in the anterior cingulate cortex and the default mode network.
Conclusions
The network-wide RSFC abnormalities we report agree with the previous findings in RRMS, the cognitive and clinical implications of which are discussed herein.
IMPACT STATEMENT
This study investigated resting state functional connectivity (RSFC) in relapsing remitting multiple sclerosis (RRMS) persons with mild disability (expanded disability status scale ≤4). Whole-brain connectome-wide multivoxel pattern analysis (MVPA) was used for assessing RSFC. Compared to healthy controls (HC), we were able to identify three regions of interest for significant differences in connectivity patterns, which were then extracted as a mask for whole-brain seed-to-voxel analysis. A reduced connectivity was noted in the RRMS group, particularly in the anterior cingulate cortex and the default mode network regions, providing insights into the RSFC abnormalities in RRMS.
... In another study, Nicholas et al. confirmed middle temporal gyrus thinning and the loss of GABAergic interneuron in layers IV and VI by examining the postmortem entorhinal cortex of patients with MS with seizures. Even though the loss of inhibitory interneurons seemed to be related to GMLs, it was not explained by inflammation and mitochondrial dysfunction within the type I gray matter lesions [46]. ...
Despite the significant differences in pathological background of neurodegenerative diseases, epileptic seizures are a comorbidity in many disorders such as Huntington disease (HD), Alzheimer’s disease (AD), and multiple sclerosis (MS). Regarding the last one, specifically, it has been shown that the risk of developing epilepsy is three to six times higher in patients with MS compared to the general population. In this context, understanding the pathological processes underlying this connection will allow for the targeting of the common and shared pathological pathways involved in both conditions, which may provide a new avenue in the management of neurological disorders. This review provides an outlook of what is known so far about the bidirectional association between epilepsy and MS.
... 10 Temporal lobdaki tip I gri cevher lezyonlarının (lökokortikal) kortikal IV ve VI tabakalardaki inhibitör internöronların kaybına neden olarak nöbet yatkınlığını artırabileceği öne sürülmüştür. 11 EEG çalışmalarında MS için özgül olacak bir bulgu saptanmamıştır. Metodolojik farklılıklar olmakla birlikte çoğu olguda saptanan bulgu fokal/jeneralize yavaşlama veya fokal/jeneralize epileptiform deşarjlardır. ...
... A further limitation of this study was the availability of neuroimaging of our patients. All MRI protocols and sequences are intrinsically poor at the evaluation of cortical grey matter, 17,23 and conventional T2 weighted MR sequences are not sensitive to intracortical lesions due their longer relaxation times and low contrast resolution compared to grey matter. 8 Cortical lesions have been found to be more common in those with RRMS with seizures compared to RRMS patients without seizures. ...
Rationale
To determine the prevalence of epileptic seizures in multiple sclerosis (MS) at an Australian tertiary hospital and to define their clinical features.
Methods
We retrospectively analysed adult patients at the Royal Melbourne Hospital electronically identified to have ICD codes for MS and seizures and/or epilepsy between 1996 to 2019, utilising paper and electronic-based records.
Results
Of the 2,125 MS patients identified, 16 (0.75%) experienced epileptic seizures during a mean follow-up period of 12.9 years. Median age of MS diagnosis (SD) was 38 (9.3) years. Four patients had relapsing remitting MS (25%), 10 secondary progressive MS (63.5%), and 2 primary progressive MS (12.5%). More than two-thirds of patients had seizure onset following the diagnosis of MS, and the majority of these had advanced disease (approximate EDSS >6) at the time of seizure onset. Focal onset-seizures occurred in 87.5% of patients with seizures.
Conclusion
The estimated prevalence of seizures in our cohort was lower than in previous studies (0.75 vs 2–4%). In most cases, seizures occurred after the diagnosis of MS in the context of advanced disease. Further studies are required to determine if MS disease modifying treatments reduce the risk of seizures in this cohort.
... Previous study described a link between increasing disease duration, severity of MS and risk of epilepsy [7]. Further studies indicated that cortical inflammation and degenerative cortical grey matter lesions, especially in the temporal lobe, could enhance the susceptibility to seizures in MS [8][9] ...
