Epilepsy and multiple sclerosis: Increased risk among progressive forms

doi:10.1016/j.eplepsyres.2009.01.009

Epilepsy Research

Volume 84, Issues 2–3, April 2009, Pages 250-253

https://doi.org/10.1016/j.eplepsyres.2009.01.009 Get rights and content

Summary

Multiple sclerosis (MS) patients are at higher risk for epilepsy. Epilepsy was frequent among our MS patients (6.55%). Progressive MS forms were associated with higher incidence of epilepsy (p = 0.021). Partial motor seizures were observed in five patients (62.5%) and generalized tonic-clonic in three (37.5%). Electroencephalogram (EEG) revealed epileptic activity in 62.5%. A high percentage of MS patients with epilepsy (37.5%) reported intoxication as the most severe form of adverse effect of antiepileptic therapy.

Introduction

Epilepsy has been reported to be more frequent among patients with multiple sclerosis (MS) than in the general population and may affect patients during early and chronic phases of their disease (Poser and Brinar, 2004). Possible etiologies of seizures in MS include edema or demyelination in the brain cortex or white matter juxtacortical junction. We reviewed previous series on MS and epilepsy (Table 1). We were also interested in comparing MS patients with epilepsy to those without epilepsy in terms of socio demographic and clinical variables and determine the frequency of epilepsy among a sample of MS patients attending the National Institute of Neurology and Neurosurgery of Mexico City (NINN).

Section snippets

Materials and methods

Patients were included from the prospective database of the MS Clinic at the NINN, a tertiary care reference center in the country. Definite MS diagnosis was established by a neurologist following Poser's and MacDonald's criteria (Poser et al., 1983, McDonald et al., 2001). The database included 290 patients, 122 were selected for the present study, we excluded patients with possible etiologic factors for epilepsy other than MS (e.g. neurocysticercosis, head trauma, neoplasia, vascular

Results

We included 122 patients with MS; eight patients (6.55%) had MS and epilepsy. We compared them with another group of 16 MS patients without epilepsy according to our study's inclusion criteria. Comparisons between groups did not show statistically significant differences regarding time of evolution of MS, age, gender, yearly number of relapses, EDSS score and MRI atrophy. The mean time of evolution was 8.1 years for cases and 6.5 years for the control group.

The progressive MS forms, either

Discussion

According to previous reports our study also reveals that epilepsy is more frequent among MS patients (Olafsson et al., 1999, Sokic et al., 2001). Results from a household survey carried out in Mexico (Cruz-Alcala and Vazquez-Castellanos, 2002) indicate that the prevalence of epilepsy was 6.8 (CI:5.1–8.5) was more common among men and children under 14 years of age and is therefore less frequent among adult women, an at risk group with a higher prevalence of definite MS. Although

References (18)

B.A. Engelsen et al.
Epileptic seizures in patients with multiple sclerosis. Is the prognosis of epilepsy underestimated?
Seizure
(1997)
P.A. Nyquist et al.
Incidence of seizures in patients with multiple sclerosis: a population-based study
Mayo Clin. Proc.
(2002)
C.M. Poser et al.
Epilepsy and multiple sclerosis
Epilepsy Behav.
(2003)
C.M. Poser et al.
The nature of multiple sclerosis
Clin. Neurol. Neurosurg.
(2004)
V. Bertol et al.
Multiple sclerosis as a cause of partial complex epilepsy
Rev. Neurol.
(1997)
Commission on Classification and Terminology of ILAE
Proposal for revised clinical and electroencephalographic classification of epilepsies and epileptics syndromes
Epilepsia
(1989)
L.E. Cruz-Alcala et al.
Prevalencia de algunas enfermedades neurológicas en la Ciudad de Tepatitlán, Jalisco
México Rev. Mex. De Neuroci.
(2002)
A. Ghezzi et al.
Epilepsy in multiple sclerosis
Eur. Neurol.
(1990)
E. Kinnunen et al.
Prevalence and prognosis of epilepsy in patients with multiple sclerosis
Epilepsia
(1986)

There are more references available in the full text version of this article.

Cited by (30)

Multiple sclerosis and seizures: A retrospective observational study in a multiple sclerosis autoimmunity center of excellence
2024, Seizure
The prevalence of epilepsy in patients with multiple sclerosis (MS) is three to six times the prevalence in the general population. Mechanisms resulting in increased seizure risk are not fully understood. Our objective is to characterize patients with MS and epilepsy regarding timing of diagnoses, MS and seizure (SZ) type, EEG findings suggesting cortical dysfunction, frequency of status epilepticus (SE), and seizure freedom.
This was a single center retrospective study. Cases were obtained via DataDirect via the University of Michigan electronic medical record from January 1, 2006 through October, 12, 2016. The University of Michigan Health System is a large academic institute with a tertiary referral center and an Autoimmunity Center of Excellence. Patients were included if chart listed one or more of the top 62 epilepsy, and one or more of the top 2 MS, most frequently entered ICD9 and ICD10 codes. Patients with alternative epilepsy etiology were excluded. 74 of 361 patients were included. We collected information regarding demographics, MS and SZ type, age at diagnosis, imaging, EEG, seizure freedom, medications, and SE.
We found a high percentage of patients with SE. Most patients with imaging had multiple lesions at seizure onset. 27/54 of patients with EEG data showed electrographic evidence of cortical dysfunction. 6/8 of EEGs in PPMS showed features consistent with cortical dysfunction, followed by 9/17 in SPMS and 11/23 in RRMS. 7/8 of patients with PPMS showed EEG evidence of temporal lobe dysfunction.
Time of seizure onset relative to MS diagnosis varied with MS type suggesting distinct pathophysiology. EEG results correspond with reports of increased cortical damage and temporal dysfunction in PPMS, but are unique as a functional modality (EEG) as indicator of gray matter dysfunction. EEG findings differed in RRMS and progressive MS suggesting possibility of supportive diagnostic marker. Our data suggests higher risk of SE in progressive MS and diminished rate of seizure freedom for MS patients with SE. We conclude that early treatment with antiseizure medication would be beneficial for MS patients with SE and with progressive MS forms and SZ, in agreement with previous studies.
An algorithm to determine the date when the McDonald criteria are met for the diagnosis of relapsing-remitting multiple sclerosis
2022, Revue Neurologique
Citation Excerpt :
Moreover, we did not take into account the possibility of symptomatic periventricular and juxtacortical lesions and considered that these lesions were always asymptomatic. Although it has been demonstrated that juxtacortical lesions could be responsible for symptoms like epileptic seizures [21] and deficits can originate from large periventricular plaques [22], these symptoms are not collected by EDMUS and consequently we could not take them into consideration. However, these types of symptoms and symptomatic lesions are not that frequent.
A patient is diagnosed with multiple sclerosis once they meet the McDonald criteria of dissemination in space and time. Studies of cohorts of patients with multiple sclerosis need a reproducible way to determine an accurate date of diagnosis. We developed an automatic data-driven algorithm to determine the date when the MacDonald criteria are met, which we validated with the Registre Lorrain des Scleroses en Plaques (ReLSEP), a regional French registry of patients with multiple sclerosis.
We developed an algorithm to determine the date of diagnosis based on clinical and paraclinical data adapted from the four versions of the McDonald criteria. For validation, the dates of diagnosis generated by the algorithm were compared with those determined by an expert physician using the patients’ files as the gold standard. We calculated the sensitivity and specificity of the algorithm to provide a date, then we tested the equivalence between the dates of the gold standard and the algorithm (two-one-sided-t-test).
The algorithm used every possibility of determining dissemination in space and time according to the four sets. The sensitivity of the algorithm was 100% for the four sets, and specificity ranged between 95 and 100%. The difference between the dates of diagnosis found by the physician and the algorithm was usually less than 2 weeks (equivalence test P < 0.0001).
The algorithm appears to be an efficient surrogate to accurately determine dates of diagnosis of multiple sclerosis in datasets of patients.
Treatment of epilepsy in multiple sclerosis
2018, Seizure
Citation Excerpt :
The prevalence of epilepsy is increased approximately threefold in multiple sclerosis (MS) [6,7]. Seizures are more common in severe MS, which suggests a causal relationship between accumulated brain damage and epilepsy [8]. In contrast to the acquired epilepsies listed above, investigators have so far focused on describing the co-existence of MS and seizures, and as pointed out in thorough reviews, little information is available on optimal AED treatment and epilepsy outcome [9].
The prevalence of epilepsy is increased in multiple sclerosis (MS), but information on AED treatment and seizure outcome is scarce. We describe epilepsy characteristics including the use of AEDs and proportion of seizure-free patients at two tertiary hospitals in Sweden.
We retrospectively studied electronic medical records of all patients with a diagnosis of MS and seizures at Sahlgrenska university hospital and Uppsala university hospital. Clinical data were reviewed until 2017.
We identified a total of 62 MS patients with at least one seizure. Median age at the first seizure (before or after MS) was 41 years (range 0–80). The most common MS disease course at the first seizure was secondary progressive MS, the neurological disability was considerable, and most patients had several MRI lesions at their first seizure. The first EEG demonstrated epileptiform discharges in 38% and unspecific pathology in 40%. Current seizure status could be determined for 37 patients. Out of these, 46% had been seizure free for more than one year at last follow-up. The majority of patients (65%) were on monotherapy at last follow-up. Carbamazepine was the most commonly used first AED, with a retention rate of 52%. No individual AED was associated with a particularly high rate of seizure freedom. The most common reason for discontinuation of the first AED was side-effects.
Seizure freedom rates were low, perhaps indicating a need for higher ambitions in management. Side effects of AEDs may be a particular concern when treating epilepsy in patients with MS.
The prevalence and characteristics of epilepsy in patients with multiple sclerosis in Nordland county, Norway
2017, Seizure
Citation Excerpt :
Because of the risk of new seizures and status epilepticus, the importance of early use of antiepileptic drugs in MS patients with epilepsy has been emphasized [8]. Others report that the majority of MS patients with epilepsy responded well to antiepileptic therapy [25,31]. In the present study, 10 of 14 patients had monotherapy for epilepsy and two had no antiepileptic treatment.
The prevalence of epilepsy among patients with multiple sclerosis (MS) has been found higher than in the general population. Although cortical pathology may be involved, the causal link between MS and epileptic seizures is still unclear. We aimed to identify and describe the patients with active epilepsy in a previously described population based MS-cohort.
Medical records of all patients with MS in Nordland County on January 1, 2010, were scrutinizing for evidence of comorbid seizures and epilepsy.
Among 431 patients with MS, we identified 19 (4.4%) with a history of seizures or epilepsy. Fourteen (3.2%) of these had active epilepsy defined as use of antiepileptic drugs or seizures within the last 5 years. One patient got epilepsy before other signs of MS. In patients with relapsing-remitting MS (RRMS) at onset and active epilepsy (n = 10), 70% had converted to secondary progressive (SPMS) at prevalence date, compared to only 35% of those without active epilepsy (p = 0.02). 43% had converted to SPMS before they got epilepsy. Attack semiology or electroencephalogram recordings indicated a focal onset of seizures in 12 of 14 (86%) with active epilepsy.
The frequency of active epilepsy among MS patients in Nordland was 3.2%, approximately 4.5 times higher than in the general Norwegian population. RRMS patients with active epilepsy had more likely converted to SPMS than patients without active epilepsy. With a high frequency of focal epilepsy, the study supports that focal MS brain pathology is the cause of the comorbid epilepsy.
Chronic demyelination-induced seizures
2017, Neuroscience
Citation Excerpt :
While MS clinical presentation is multifarious, epidemiological studies show that MS patients are three to six times more likely to develop epileptic seizures than the overall population, with incidence rising with MS duration (Engelsen and Grønning, 1997; Poser and Brinar, 2003; Lund et al., 2014; Marrie et al., 2015). Seizures in MS may signal disease onset or relapse in a subset of patients (Allen et al., 2013; Uribe-San-Martin et al., 2014) and are associated with diminished cognitive function (Calabrese et al., 2012), fulminant disease course, and accelerated time to disability (Martinez-Juarez et al., 2009; Nicholas et al., 2016). However, despite the increased occurrence of seizures among MS patients, little research exists probing their pathogenesis.
Multiple sclerosis (MS) patients are three to six times more likely to develop epilepsy compared to the rest of the population. Seizures are more common in patients with early onset or progressive forms of the disease and prognosticate rapid progression to disability and death. Gray matter atrophy, hippocampal lesions, interneuron loss, and elevated juxtacortical lesion burden have been identified in MS patients with seizures; however, translational studies aimed at elucidating the pathophysiological processes underlying MS epileptogenesis are limited. Here, we report that cuprizone-mediated chronically demyelinated (9–12 weeks) mice exhibit marked changes to dorsal hippocampal electroencephalography (EEG) and evidence of overt seizure activity. Immunohistochemical (IHC) analyses within the hippocampal CA1 region revealed extensive demyelination, loss of parvalbumin (PV⁺) interneurons, widespread gliosis, and changes in aquaporin-4 (AQP4) expression. Our results suggest that chronically demyelinated mice are a valuable model with which we may begin to understand the mechanisms underlying demyelination-induced seizures.
Gray matter damage in multiple sclerosis: Impact on clinical symptoms
2015, Neuroscience
Citation Excerpt :
The impact of cortical lesions on cognitive functioning is further illustrated by the finding that cortical lesions were found in patients with cognitive impairment as the presenting clinical symptoms of MS (Coebergh et al., 2010). Besides physical disability and cognitive impairment, epileptic seizures occur in patients with MS. Prevalence numbers of seizures in MS patients range from 0.5% to 8.3%, which is roughly three times higher than in the general population (Ghezzi et al., 1990; Moreau et al., 1998; Sokic et al., 2001; Nyquist et al., 2001; Gambardella et al., 2003; Poser and Brinar, 2003; Koch et al., 2008; Martinez-Juarez et al., 2009; Catenoix et al., 2011; Uribe-San-Martin et al., 2014). Most of the more dated research shows inconsistent results of the relation between (sub)cortical lesions and epileptic seizures (Ghezzi et al., 1990; Thompson et al., 1993; Truyen et al., 1996; Moreau et al., 1998; Sokic et al., 2001; Gambardella et al., 2003; Poser and Brinar, 2003; Uribe-San-Martin et al., 2014).
Traditionally, multiple sclerosis (MS) is considered to be a disease primarily affecting the white matter (WM). However, the development of some clinical symptoms such as cognitive impairment cannot be fully explained by the severity of WM pathology alone. During the past decades it became clear that gray matter (GM) damage of the brain is also of major importance in patients with MS. Thanks to improved magnetic resonance imaging techniques, the in vivo detection of GM pathology became possible, enabling a better understanding of the manifestation of various clinical symptoms, such as cognitive impairment. Using higher field strengths and specific sequences, detection of cortical lesions was increased. However, despite these improvements, visualization of cortical MS lesions remains difficult (only about 30–50% of histopathologically confirmed lesions can be detected at 7 Tesla magnetic resonance imaging (MRI)). Furthermore, more research is needed to understand the exact interplay of cortical lesions, GM atrophy and WM pathology in the development of clinical symptoms. In this review, we summarize the historical background that preceded current research and provide an overview of the current knowledge on clinical consequences of GM pathology in MS in terms of disability, cognitive impairment and other clinically important signs such as epileptic seizures.

View all citing articles on Scopus

View full text

Short communicationEpilepsy and multiple sclerosis: Increased risk among progressive forms

Summary

Introduction

Section snippets

Materials and methods

Results

Discussion

Seizure

Mayo Clin. Proc.

Epilepsy Behav.

Clin. Neurol. Neurosurg.

Multiple sclerosis as a cause of partial complex epilepsy

Rev. Neurol.

Proposal for revised clinical and electroencephalographic classification of epilepsies and epileptics syndromes

Epilepsia

Prevalencia de algunas enfermedades neurológicas en la Ciudad de Tepatitlán, Jalisco

México Rev. Mex. De Neuroci.

Epilepsy in multiple sclerosis

Eur. Neurol.

Prevalence and prognosis of epilepsy in patients with multiple sclerosis

Epilepsia

Short communication
Epilepsy and multiple sclerosis: Increased risk among progressive forms