Seizures In Multiple Sclerosis Research Articles

Incidence and determinants of seizures in multiple sclerosis: a meta-analysis of randomised clinical trials

BackgroundSeizures are reported to be more prevalent in individuals with multiple sclerosis (MS) compared with the general population. Existing data predominantly originate from population-based studies, which introduce variability in methodologies...

Seizures in Multiple Sclerosis are, above all, a Matter of Brain Viability

Objectives: Most patients with Multiple Sclerosis (MS) never have a seizure, although they are at risk for seizures since the onset of MS. This paradox leads us to suppose that MS plays a minor role in seizure generation and epileptogenesis. Methods: Qualitative study using data triangulation and inductive content analysis. A comprehensive literature search was carried out in four electronic databases (MEDLINE, Embase, Web of Science, and Google Scholar). Results: In MS patients, unprovoked seizures occur rarely (in about 3 percent of cases). Pediatric MS involves seizures more common than adult or late-onset MS. In general, children with seizures do not have poorer MS prognoses than children without seizures. Contrary to the general population, seizures do not peak in older MS patients. Since the use of disease-modifying therapies in the treatment of MS (i.e., since 1993), the frequency of seizures in MS patients has not changed considerably. Epilepsy syndrome cannot be recognized in MS patients with seizures. As a rule, seizures in MS are not difficult to treat. A sudden unexpected death in MS patients with seizures has not been observed more commonly than in the general epilepsy population. A disruption of the blood–brain barrier is the most obvious proconvulsive factor of MS. However, neither MS relapses nor a high rate of MS relapses is normally accompanied by seizures. Structural brain abnormalities usually accumulate over the course of MS. However, a high brain magnetic resonance imaging lesion load does not have a substantial impact on seizure occurrence in MS. Conclusion: MS does not have a major role in seizure generation and epileptogenesis. In most cases, the seizure-promoting effects of MS can be successfully counteracted by the brain´s protective mechanisms.

Prognostic impact of epileptic seizures in multiple sclerosis varies according to time of occurrence and etiology.

Epileptic seizures occur more often in patients with multiple sclerosis (MS) than in the general population. Their association with the prognosis of MS remains unclear. This study was undertaken to evaluate whether epileptic seizures may be a prognostic marker of MS disability, according to when the seizure occurs and its cause. Data were extracted from a population-based registry of MS in Lorraine, France. Kaplan-Meier curves and log-rank tests were used to compare the probability of different levels of irreversible handicap during the course of MS in patients who experience epileptic seizures or do not, according to the chronology and the cause of the first epileptic seizure. Among 6238 patients, 134 had experienced at least one epileptic seizure (2.1%), and 82 (1.2%) had seizures secondary to MS. Patients with epileptic seizure as a first symptom of MS (14 patients) had the same disease progression as other relapsing-remitting MS patients. Patients who developed epileptic seizures during the course of MS (68 patients) had a higher probability of reaching Expanded Disability Status Scale=3.0 (p= 0.006), 6.0 (p= 0.003), and 7.0 (p= 0.004) than patients without an epileptic background. Patients with a history of epileptic seizures unrelated to MS also had a worse prognosis than patients without an epileptic background. Epileptic seizures might be viewed as a "classic MS relapse" in terms of prognosis if occurring early in MS, or as a marker of MS severity if developing during the disease. Epileptic diseases other than MS may worsen the course of MS.

Seizures and epilepsy in multiple sclerosis, aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease.

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.

The prevalence of epileptic seizures in multiple sclerosis in a large tertiary hospital in Australia.

RationaleTo determine the prevalence of epileptic seizures in multiple sclerosis (MS) at an Australian tertiary hospital and to define their clinical features.MethodsWe 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.ResultsOf 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.ConclusionThe 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.

Epileptic seizures in multiple sclerosis: prevalence, competing causes and diagnostic accuracy

BackgroundMultiple sclerosis (MS) is accompanied by an increased risk of epileptic seizures, but data with a detailed description of the competing causes are lacking.MethodsWe aimed to describe a cohort of patients with both MS and epileptic seizures in a retrospective, population-based study.ResultsWe included 59 out of 2285 MS patients who had at least one epileptic seizure. Out of them, 22 had seizures before the diagnosis of MS, whereas epileptic seizures occurred after MS diagnosis in 37 patients, resulting in a total prevalence of epileptic seizures in MS of 2.6%. Competing causes could be found in 50.8% (30/59) of all patients, with 40.9% (9/22) compared to 56.8% (21/37) of the MS patients with seizures before vs after MS diagnosis. The main alternative causes were traumatic brain injury and cerebral ischemia accounting for more than 30% of the patients, with no difference between the subgroups. 33.3% and 55.6% of MS patients with seizures before/after MS diagnosis had documented pathological EEG alterations. ConclusionA remarkable percentage of MS patients with epileptic seizures do have alternative competing causes at the time of the first seizure. A detailed diagnostic setup including patient history, EEG and MRI is recommended in the evaluation and choice for the best treatment.

P 3 Cerebellar gray matter volume decrease is associated with epileptic seizures in multiple sclerosis

Background Prevalence rates of epileptic seizures are three times higher in patients with multiple sclerosis (MS) compared to healthy controls ( van Munster et al., 2015 ). There is some evidence of gray matter (GM) as well as white matter (WM) lesions associated with epilepsy in MS ( van Munster et al., 2015 ). Here, we compared regional GM volume decrease using voxel based morphometry (VBM) to compare MS patients with and without epilepsy. Methods MRI images of 30 MS patients (15 with, 15 without epilepsy, matched due to disease duration, disease course, EDSS and age) were analyzed using voxel based morphometry. Second level analysis was done comparing regional GM volume in MS patients without compared to with epileptic seizures. Results MS-patients with epilepsy had regional GM volume decrease in the cerebellum compared to MS patients without epilepsy, mainly in the posterior lobe. Neither cerebral or deep GM structures revealed significant regional GM volume decrease. Discussion There is some evidence of hippocampal GM pathology associated with epilepsy ( Nicholas et al., 2016 ). In contrast, our VBM analyses did not reveal any association to cortical or subcortical GM volume decrease. Against our expectations, we found significant cerebellar GM volume decrease in the patients with, compared to without epileptic seizures. Interestingly, there is some evidence of cerebellar lesions generating seizures ( Foit et al., 2016 ), cerebellar abnormalities in idiopathic generalized epilepsy ( Li et al., 2010 ) as well as a cerebellar mediated, inhibitory effect on hippocampal seizures ( Krook-Magnuson et al., 2014 ). Our data has to be confirmed in larger samples, but at least are indicating a possible role of the cerebellum in MS patients with epilepsy.

Unprovoked seizures in multiple sclerosis: Why are they rare?

IntroductionThe frequency of seizures in patients with multiple sclerosis (MS) ranges from 1.5% to 7.8% and is considerably more common than chance events. The etiopathogenesis of seizures in MS is still poorly understood.MethodA review of the literature on seizures and MS using PubMed.ResultsCortical gray matter involvement appears to be an all‐too‐common pathological finding in MS to play a primary role in the pathogenesis of seizures in MS patients. There is no clear relationship between seizures and the severity of MS. In approximately 10% of cases, a seizure is actually an initial neurological symptom of MS.ConclusionSearching for coherence in the occurrence of unprovoked seizures in MS directs attention to the dichotomy in MS pathology characterized by a complex intertwining of neuroinflammatory and neurodegenerative processes. The appearance (or nonappearance) of seizures in MS in relation to disease activity and disease progression indicates a distinct clinical phenotype of MS that opens up new perspectives in MS research.

Risk factors for unprovoked epileptic seizures in multiple sclerosis: a systematic review and meta-analysis.

The role of different factors in influencing the risk of seizures during multiple sclerosis (MS) is not known. To perform a systematic review and meta-analysis of risk factors for epilepsy during MS. Pubmed, Google scholar, and Scopus databases were searched. Articles published in English (1986-2016) were included. Nine studies were included (3 retrospective cohort and 6 case-control) enrolling 2845 MS patients (217 with epilepsy; 7.6%). MS patients with epilepsy had a younger age at onset compared to MS patients without seizures (difference in means=-5.42years, 95% CI -7.19 to -3.66, p<0.001). Mean EDSS value at inclusion tended to be higher in patients with epilepsy, without reaching statistical significance (difference in means=0.45, 95% CI -0.01 to 0.91, p=0.054). No differences were observed in sex distribution (OR=0.94, 95% CI 0.51-1.72, p=0.83) and clinical form (OR=1.03, 95% CI 0.33-3.21, p=0.96). Two studies evaluated presence and number of cortical lesions as a risk factor for epilepsy in MS using different MRI techniques: in one study, cortical lesions were more frequently observed in patients with epilepsy (OR=7.06, 95% CI 2.39-20.8; p<0.001). In the other, cortico-juxtacortical lesions were more frequently observed in patients with epilepsy (OR=2.6, 95% CI 1.0-6.5; p=0.047). Studies about risk factors for epilepsy during MS are heterogeneous. Compared to MS patients without seizures, patients with epilepsy have an earlier MS onset and a higher EDSS score after similar disease duration. Clinical form of MS and sex do not predict the appearance of seizures.

Temporal lobe cortical pathology and inhibitory GABA interneuron cell loss are associated with seizures in multiple sclerosis

Background: Seizures are recognised in multiple sclerosis (MS), but their true incidence and the mechanism by which they are associated with MS is unclear. Objective: 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. Methods: We evaluated 255 individuals from the UKMSTB. A subset underwent analysis of cortical thickness, grey matter lesion (GML) (type and number) and cortical neuronal numbers (total and GABAergic). Results: A total of 37/255 patients had seizures (14.5% lifetime incidence); in 47% they were associated with concurrent infection. In those with seizures, death and wheelchair use occurred earlier and in 59% seizures developed after 15 years of disease. Seizures were associated with Type 1 GMLs and reduced cortical thickness in the middle temporal gyrus. Localised selective GABAergic interneuron loss in layers IV and VI was related to GMLs but was not explained by the presence of inflammation or by mitochondrial dysfunction within Type I GMLs. Conclusion: We confirm that seizure frequency rises in MS. Type I GMLs in the temporal lobe underlie a loss of inhibitory interneurons in cortical layers IV and VI and these changes could together with concurrent infection enhance susceptibility to seizures.

Cortico-juxtacortical involvement increases risk of epileptic seizures in multiple sclerosis

Previous studies have reported an increased risk for epileptic seizures in multiple sclerosis (MS) patients. However, data on the pathogenesis of seizures remain inconclusive. The aim of our study is to evaluate prevalence, clinical and paraclinical features of epileptic attacks in our MS cohort and to search MS-specific risk factors for epileptic seizures. In this cohort of 428 MS patients, 13 patients were identified with epileptic seizures occurring at any point during the course of MS including at MS onset. As a control group, we selected 26 MS patients without seizures and matched for gender, age and date of MS onset. We compared demographic features and clinic-radiological findings between the both groups. Thirteen patients (3%) were identified as having epileptic attacks. Ten patients (77%) experienced focal seizures, half of whom had confirmed secondary generalization. We did not find an association between seizures and disease course. Most patients had a single or few (2-5) seizures. MS patients with seizures had a significantly higher number of cortical and juxtacortical lesions on T2-weighted/fluid attenuation inversion recovery magnetic resonance imaging than control group [OR = 2.6 CI95% (1.0-6.5); P = 0.047]. Our findings support a credible role of cortical and juxtacortical involvement in the development of epileptic seizures in MS.

Epileptic seizures in multiple sclerosis: a population-based survey in Iran

No large population-based survey has until now been carried out on the linkage of epilepsy (EP) and multiple sclerosis (MS) either in the middle-east or in Asia. In this retrospective population-based study (April 2003 to July 2010) on the total Isfahan cohort of 3,522 Iranian MS patients, we looked for EP/MS patients and compared their features with 1,665 non-EP/MS cases. We identified 105 cases, though, 24 were excluded for an implausible EP/MS link. Among 81 (2.3 %) eligible cases, EP occurred (1) within a mean duration of 5.6 ± 5.4 years after the development of MS in 64 cases (79 %); (2) at MS onset as the presenting symptom in five cases (6.2 %); and, (3) by a mean duration of 4.3 ± 4.3 years prior to onset of MS in 12 patients (14.8 %). The overall mean ages at MS onset and at the first seizure episode were 28.5 ± 11.2 years and 32.5 ± 14.0 years, respectively. Regarding the age at onset of MS, 12.3 % of EP/MS patients were classified as early-onset; 81.5 % as adult-onset; and 6.2 % as late-onset. Such frequencies were statistically different (P < 0.0001) from those of the 1,665 control non-EP/MS patients (5.9; 93.0 and 1.1 %, respectively). Regarding the pattern of MS, EP/MS patients were classified as relapsing-remitting, secondary progressive, and primary progressive in 60.5, 25.9, and 13.6 %, respectively. This configuration differed (P < 0.0001) from that of non-EP patients (87.9; 6.3 and 5.7 %, respectively). Our results are suggestive of differences between EP/MS and non-EP/MS cases as regards the proportion of MS patterns and age-at-onset classifications.

Status Epilepticus Associated With Dalfampridine in a Patient With Multiple Sclerosis

Status Epilepticus Associated With Dalfampridine in a Patient With Multiple Sclerosis

Unprovoked seizures in multiple sclerosis and systemic lupus erythematosus: A population-based case–control study

To study the risk of developing unprovoked seizures among patients with multiple sclerosis (MS) and systemic lupus erythematosus (SLE), we used 1885 new onset seizure cases, 15,080 controls and defined exposure as a hospital discharge diagnosis of MS or SLE. The odds ratio with 95% confidence interval was 3.7 (CI 1.2-11.0) for MS and 8.0 (2.2-30.0) for SLE, suggesting an increased risk of unprovoked seizures in patients with both these diagnoses.

Multiple sclerosis, seizures, and antiepileptics: role of IL-18, IDO, and melatonin

To review the treatment and mechanisms underlying the increased prevalence of seizures associated with multiple sclerosis (MS). We carried out an extensive review of the literature pertaining to seizures in MS. We propose that an increase in interleukin-18, and its associated induction of indoleamine 2, 3-dioxygenase and quinolinic acid, mediates seizure activity in MS at least in part via an increase in interferon-gamma (IFNg). Increased kynurenine pathway activity decreases the availability of serotonin and melatonin. Increases in blood-brain barrier and circumventricular organ permeability are linked to these changes. Antiepileptic drugs modulate wider MS symptomatology, interacting with melatonin and vitamin D3. This manuscript provides a framework for the wider understanding and treatment of seizures in MS and wider MS symptomatology.

Seizures in Patients with Multiple Sclerosis

Seizures have been recognized to occur in multiple sclerosis (MS) since early descriptions of the disease. Various studies have attempted to determine the incidence and prevalence of seizures in MS; although they differ in the reported prevalence, seizures do appear to be more common in MS cohorts than in the general population. The pathological underpinning of seizures in MS remains indeterminate. Cortical and subcortical demyelination and inflammation may explain the increased frequency of seizures in MS, although this hypothetical correlation remains to be proven. Management of seizures in MS is similar to the management of seizures in other patients. Consideration of the underlying neurological deficits related to MS may be necessary, and dosages of antiepileptic drugs should be adjusted if increased sensitivity to the adverse effects of these agents or interaction with other centrally acting medications is suspected. The prognosis of epilepsy in patients with MS remains uncertain, with some studies suggesting a more favourable prognosis than others.

Treatment of seizures in multiple sclerosis

Epileptic seizures occur in only a minority of patients with multiple sclerosis (MS), but can have serious consequences. The available literature suggests an association of seizures in MS with cortical and subcortical demyelinating lesions, which suggest that seizures in MS are probably most often symptomatic rather that idiopathic. It is currently unknown whether patients with MS should be treated differently from other patients with epileptic seizures. To evaluate the efficacy and safety of antiepileptic treatments in patients with MS. We searched for double-blind, single-blind or unblinded randomised controlled trials on antiepileptic treatment in patients with MS through electronic searches of The Cochrane Multiple Sclerosis Group's and Cochrane Epilepsy Group's Trials Registers, Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue 1), MEDLINE (From 1966 - Jan 2008) and EMBASE (From 1974 - Jan 2008). Double-blind, single-blind or unblinded randomised controlled trials on antiepileptic treatment in patients with MS. Searches yielded a total of 379 citations (CENTRAL: 20, MEDLINE: 264, EMBASE: 95). We perused titles and abstracts for relevance and independently excluded all 379 citations as clearly not meeting the inclusion criteria. We found no studies meeting our inclusion criteria. Well-designed randomised controlled trials are needed to guide clinical practice. Such trials should preferably contain a head-to-head comparison of antiepileptic drugs in patients with MS.

Seizures in multiple sclerosis

Seizures have long been recognized to be part of the disease spectrum of multiple sclerosis (MS). While they occur in only a minority of patients with MS, epileptic seizures can have serious consequences. The treatment of MS can be epileptogenic, and antiepileptic treatment can conversely worsen the symptoms of MS. In this article we present an overview of the current literature on the epidemiology, clinical presentation, pathology, imaging, prognosis and treatment of epileptic seizures in MS.

Epileptic seizures, cranial neuralgias and paroxysmal symptoms in remitting and progressive multiple sclerosis.

The occurrence of a first epileptic seizure, spinal or brainstem paroxysmal symptom and cranial neuralgia during 25 years after onset was studied in a population-based multiple sclerosis (MS) cohort of 255 patients. Epileptic seizures occurred in 20, paroxysmal symptoms in 11 and cranial (trigeminal, intermedius, retroauricular or occipital) neuralgia in 11 patients. The yearly incidence of epileptic seizures in MS was estimated to be 349(+/-153)/100,000, approximately seven times higher than in the general population. The yearly incidence of a first paroxysmal symptom in the present material was calculated to be 190 cases in 100,000 MS patients, and the yearly incidence of cranial neuralgia was 189 cases in 100,000 MS patients. The epileptic seizures were more frequent during the progressive course than in the relapsing-remitting (RR) course. The frequencies of paroxysmal symptoms and cranial neuralgia did not differ between these two disease courses. A coincidence of epileptic seizures and a decline in cognitive functioning not seen among patients with paroxysmal symptoms was found The relatively late occurrence of epileptic seizures indicates that the frequency of epileptogenesis, known to involve neuronal damage, increases in the later stages of MS.

Epileptic and non-epileptic seizures in multiple sclerosis.

Knowledge concerning the relationship between multiple sclerosis and epilepsy is reviewed. Epidemiological studies have established that epileptic seizures are more frequent in multiple sclerosis than predicted by chance. Partial epilepsies with focal seizures often with atypical symptoms and with or without secondary generalisation are the usual pattern. In the survey special emphasis is laid on the direct correlation between paroxysmal phenomena and plaques now demonstrable by modern imaging techniques. These images have shown that epileptic seizures can be caused by cortical and subcortical lesions and by their accompanying oedema. We extend the review to non-epileptic paroxysmal symptoms, such as tonic spasm, which may be confused with epileptic seizures. As far as they are supported by data, recommendations for diagnosis and therapy are given. Open questions are identified and issues for further research are suggested.