Less used medication contained lorazepam, gabapentin, phenytoin, and lacosamide. Both mono- and polytherapies were prescribed, with nine patients requiring only one drug to treat their seizures. All other patients received at least two different medications during the assessment period. Only one patient did not receive any antiepileptic drug. Some patients had an excellent response to anticonvulsive therapy, whereas the epilepsy of the other part of the group of patients seemed to be difficult to control and was characterized by recurrent seizures of varying frequencies.
In seven patients the emergence of seizures could be controlled. The other seven patients seemed to suffer from drug-resistant seizures.
One more patient developed recurrent seizures probably because of non-compliant drug use. Five patients had their first seizure and did not present to the clinic again prior to the time of data collection, so it remains unclear whether these patients developed more seizures under antiepileptic therapy or not. Documentation was incomplete for two of the patients and therefore no statement regarding therapy response can be made. Unfortunately, it was difficult to compare epilepsy outcome based on the use of immunomodulatory or symptomatic MS treatment due to irregular presentation of some patients at the Department of Neurology of the University of Regensburg resulting in insufficient information being available on this subject.
Nevertheless, an increased frequency of seizures could be determined in two individuals whose medication was changed to fingolimod. The characteristics of the 22 described individuals are presented in Table 1. Table 1. Overview of the MS patients with epileptic seizures at the Department of Neurology of the University of Regensburg which have presented themselves between and Even though seizures only affect a minority of patients with MS, they are still a serious problem 5.
The occurrence of seizures has previously been considered as part of the disease spectrum of MS. Several studies indicate that the risk of developing seizures is up to six times higher in MS patients compared to the general population 6 — 9. It is well-known that MS is not only a disease of the white matter of the cerebral cortex, but also affects the gray matter 16 , 17 and that atrophy and lesions in this part of the brain are more frequent than previously suggested 4.
This leads to the assumption that cortical and subcortical lesions as well as surrounding oedema in MS may play an epileptogenic role. An increased number of these lesions in MS patients with comorbid seizures and epilepsy has been reported as compared to MS patients without seizures 5 , 12 , NMR-tomographic studies have shown an association between gray matter lesions and the appearance of epilepsy 7 , 19 — A recent study of Burman et al. The increased lesion load possibly results in a demyelinated area with a higher risk of epileptogenic potential Furthermore, some medications used in treating MS, such as baclofen or interferon beta, may increase the risk of generating seizures.
The proconvulsive properties of some drugs could be due to metabolic interference with antiepileptic drugs or due to direct neurotoxic effects 25 , While the prevalence of epilepsy in the general population is about 0. Based on several studies by different authors, prevalence rates of seizures or epilepsy between 0. We observed a prevalence for seizures of 1. Accordingly, the frequencies reported by us are lower than the frequency of people having MS and seizures or epilepsy previously reported in other studies as shown in Table 2.
Table 2. MS patients observed in other studies of different MS centres and countries and the amount of concomitant seizures in these patients. Such varying results could be due to selection bias and differences in methods, definitions and diagnostic criteria 30 , For example, the accuracy of the MS diagnosis as well as the definition of epilepsy and its distinction toward non-epileptogenic, paroxysmal manifestations of MS, such as tonic spasm of the extremities, play a crucial role Moreover, the different composition of the study populations may have also contributed to the varying results.
Some of the listed studies might have included all MS patients with seizures independent of these having other reasons for developing seizures than MS. For example, Catenoix et al. It has also to be noted that some studies might have included MS patients who developed their first seizure long before MS onset, making a relation between the two diseases rather unlikely Furthermore, it should be emphasized that no strict diagnostic criteria for MS existed before and that magnetic resonance imaging MRI was first introduced in the diagnostic criteria of MS in the mids It cannot be excluded that the prevalence rate may have been underestimated because of the retrospective design of our study.
With a percentage of The same gender preference was shown in other studies by various authors 6 , 7 , 27 , 35 , 37 , suggesting an increased occurrence of epilepsy especially in women with MS.
In addition, in this study, patients presented with an average age of Other studies too reported their patients being relatively young when MS was diagnosed for the first time 10 , This in turn raises the suspicion that the risk of developing epilepsy is highest among the younger MS patients 10 , However, as MS is generally more likely to affect younger people and among these predominantly women, these numbers probably reflect the distribution in the general MS population 2 , 6 , Symptoms of these functional systems are among others the most common disease manifestations in MS patients Considering the time of first manifestation of seizures and epilepsy in MS patients, it must be noted that seizures may occur in any subtype of MS and at any time during the disease course.
Furthermore, the appearance of epileptic symptoms is possible even before the onset of MS. However, it should be emphasized that MS itself can exist long before becoming clinically apparent for the first time 5 , 11 , No PPMS patients were present in our cohort but PPMS patients have been reported in other studies in which the presentation of MS and epilepsy has been investigated 6 , 10 , 21 , 22 , 25 , 26 , 28 , 30 , As already mentioned, focal pathologies of the brain occurring in MS patients, which are likely supposed to cause increased excitability of the cerebral cortex, might be the underlying cause of seizures in these patients 7 , 20 , The lower frequency of seizures in patients with PPMS may be linked to the fact that these patients show a lower burden of cerebral lesions, predominantly in form of non-periventricular distribution Various studies have shown that epilepsy usually occurs in early stages of MS Seizures may be the first symptom of MS, however most seizures occur during the disease and thus after diagnosis of MS The present study confirms that the majority of seizures occur in patients already diagnosed with MS.
Seizures occurred about However, some studies also reported a larger range between the first manifestation of MS and occurrence of epilepsy which are in line with the range presented in the current study 25 , 33 , These differences may be explained by the fact that some of these studies are older and were published at a time when uniform diagnostic criteria for MS were not yet available and diagnostic options e. Consequently, this may have led to a later diagnosis of MS and a shorter duration until the first onset of epilepsy.
In addition, the patients' better understanding of their disease, their education, the use of self-help groups and a resulting more conscientious and cautious lifestyle as well as progress in therapy, especially immunotherapy, may cause a later appearance of seizures in MS patients Since there was no patient in this study who showed seizures as the first symptom, it is suggested that the likelihood of developing seizures and epilepsy may rise with the duration of MS and the number of lesions Some authors mention that, although all types of seizures may occur in MS, seizures of focal onset are more common than tonic-clonic seizures of unknown onset, with a high proportion of focal to bilateral tonic-clonic seizures among seizures of focal onset 7 , 18 , 27 , This is in line with the results of our study, in which Only This supports the assumption that local inflammation and lesion evolution in the brain could be the cause of developing epilepsy when already having MS 10 , Three of the five patients with tonic-clonic seizures of unknown onset were classified as having unknown epilepsy.
Many chronic conditions, such as Alzheimer's disease of the brain, various dystrophies of the muscles, psoriasis of the skin, and others, involve inflammation, and one needs convenient tools to help categorize different types of inflammation. Activation of the spinal reflex pathway promotes urine retention. Furthermore, a relation between certain immunomodulatory therapies and the development and frequency of seizures in MS patients seems possible but remains to be proven in further studies due to limited data availability at present. Thus, it is more likely to provide instructive parallels for understanding the pathology and pathophysiology of MS. Conclusion Based on the results obtained in this study, it was concluded that MSFC was sensitive to evaluate the functional performance in subjects with the relapsing-remitting form of MS when compared with healthy subjects. One starts with clustering the sera and the antigens of the full data set and identify all stable clusters of either sera or antigens.
No patients with a proven generalized epilepsy were identified Whether and to what extent the manifestation of seizures and epilepsy in MS patients influences the clinical course and the long-term prognosis of the MS has not been sufficiently clarified 7 , 9 , Patients with MS and simultaneously existing seizures or epilepsy show a higher EDSS score as compared to MS patients without epileptic manifestations 18 , 28 , In addition, seizures are associated with the earlier loss of walking ability and, consequently, use of a wheelchair, as well as earlier death When studying the patients' medical records, it was apparent that seizures differed in both severity and frequency, so that some patients where more affected than others by their disease.
In addition, it could be seen that epilepsy in some patients was halted when using anticonvulsive therapy while the epilepsy of the other patients seemed to be drug resistant and difficult to control by medical therapies, so these patients presented recurring seizures. Similar findings were reported in a study by Dagiasi et al.
The benign form contains an unchanged or even decreasing frequency of seizures and a regular pattern of their appearance. The progressive course, however, describes a frequent occurrence of seizures and a constant development of new types of seizures In our study, Five patients had their first seizure after developing SPMS, which leads to the assumption that the increased load of cerebral lesions occurring in MS patients may act as a risk factor for the development of epilepsy.
This on the other hand suggests that epilepsy as a comorbidity of MS could lead to a higher severity of the disease, to an increasing disability and to an earlier development of SPMS. While some authors believe that seizures in MS are usually harmless and show an adequate response to antiepileptic therapy, Engelsen et al. Possibly there is a higher risk for developing status epilepticus including all its serious consequences in patients with MS. As described above, in our study, status epilepticus was confirmed in three individuals, whereas for one patient the data were inconclusive.
It is possible that MS patients with concomitant seizures experience a more severe disease course as MS patients without seizures. Thus, seizures could probably be considered as an additional factor aggravating disease. This might be because seizures can affect disability itself and lead to increased neuronal damage with the resulting consequences Whether the appearance of both disorders is coincidental or MS acts as a non-specific trigger for developing seizures and epilepsy or indeed is the direct cause of seizures is still under debate However, the increased incidence of epileptogenic activities in MS patients as compared to the non-MS population suggests a causal relationship between the two diseases The findings of this study indicate that there is a higher risk of developing seizures when having MS as compared to the general population.
The fact that in most cases, seizures occurred after the first manifestation of MS indicates that they may be the consequence of MS. Furthermore, a relation between certain immunomodulatory therapies and the development and frequency of seizures in MS patients seems possible but remains to be proven in further studies due to limited data availability at present. Moreover, the high frequency of RRMS and SPMS as well as of focal epilepsy supports the idea that cortical lesions occurring in MS patients may play an important role in comorbid epilepsy.
This may indicate that epilepsy is a marker of more aggressive forms of MS but could also suggest that progressive forms of MS are more likely to generate seizures. RW outlined the subject of the research theme. RW and AS obtained ethical permission to perform the research. AS and RW searched the patient files and collected the original data. AS analyzed the data. AS and RW interpreted literature and wrote the manuscript. AS and RW agreed to be accountable for all aspects of the work.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Pathology of demyelinating diseases. Annu Rev Pathol.
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