|
 
 |
| REVIEW ARTICLE |
|
| Year : 2021 | Volume
: 12
| Issue : 1 | Page : 14 |
|
Prevalence of seizure/epilepsy in patients with multiple sclerosis: A systematic review and meta-analysis
Omid Mirmosayyeb1, Vahid Shaygannejad2, Nasim Nehzat1, Aida Mohammadi3, Mahsa Ghajarzadeh4
1 Isfahan Neurosciences Research Center, Isfahan University of medical sciences, Isfahan; Universal Council of Epidemiology (UCE), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences, Tehran, Iran
2 Isfahan Neurosciences Research Center; Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3 Universal Council of Epidemiology (UCE), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences, Tehran, Iran
4 Universal Council of Epidemiology (UCE), Universal Scientific Education and Research Network (USERN); Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| Date of Submission | 22-Feb-2020 |
| Date of Acceptance | 22-Apr-2020 |
| Date of Web Publication | 24-Feb-2021 |
Correspondence Address:
Mahsa Ghajarzadeh
Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran; Universal Council of Epidemiology (UCE), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences, Tehran; Imam Hospital, Tehran
Iran
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijpvm.IJPVM_75_20
Background: Seizure and epilepsy are among the initial symptoms of multiple sclerosis (MS), yet different prevalence rates are reported for them in the previous studies. The goal of this systematic review is to estimate the pooled prevalence of seizure and epilepsy in patients with MS. Methods: We searched PubMed, Scopus, EMBASE, Web of Science, google scholar, and gray literature including references from identified studies and conference abstracts published up to October 2019. The search strategy included the MeSH terms and text words as ((Epilepsies OR Seizure Disorder OR Seizure Disorders OR Awakening Epilepsy OR Epilepsy, Awakening OR Epilepsy, Cryptogenic OR Cryptogenic Epilepsies OR Cryptogenic Epilepsy OR Epilepsies, Cryptogenic OR epilepsy OR seizure) AND (Multiple Sclerosis OR Sclerosis, Multiple) OR Sclerosis, Disseminated) OR Disseminated Sclerosis) OR MS (Multiple Sclerosis)) OR Multiple Sclerosis, Acute Fulminating). Results: The literature review resulted in 4860 articles; 2593 articles remained after eliminating the duplicates. For the final analysis, 39 articles were included, 9 of which were conference abstracts. The pooled prevalence of seizure in MS cases was 2%, 95% confidence interval (CI)(1%-3%) (I2 = 91.8%, P < 0.001). The pooled prevalence of epilepsy in MS cases was 3%, 95% CI (2%-4%) (I2 = 92.9%, P < 0.001). The pooled prevalence of epilepsy in Asia, Europe, and America was 6%, 3%, and 3%, respectively. The level of heterogeneity decreased after subgroup analysis in Asian and American subgroups. Meta-regression analysis showed continent is not a source of heterogeneity (coefficient = -0.007, P = 0.6). Conclusions: The result of this systematic review shows that the pooled prevalence of seizure and epilepsy among MS patients is 2% and 3%, respectively.
Keywords: Epilepsy, multiple sclerosis, prevalence, seizures
How to cite this article:
Mirmosayyeb O, Shaygannejad V, Nehzat N, Mohammadi A, Ghajarzadeh M. Prevalence of seizure/epilepsy in patients with multiple sclerosis: A systematic review and meta-analysis. Int J Prev Med 2021;12:14 |
How to cite this URL:
Mirmosayyeb O, Shaygannejad V, Nehzat N, Mohammadi A, Ghajarzadeh M. Prevalence of seizure/epilepsy in patients with multiple sclerosis: A systematic review and meta-analysis. Int J Prev Med [serial online] 2021 [cited 2022 Aug 15];12:14. Available from: https://www.ijpvmjournal.net/text.asp?2021/12/1/14/310146 |
| Introduction | |  |
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system, with a higher prevalence in women.[1],[2] It has a wide range of negative consequences on personal, social, occupational, and marital aspects of life.[3] MS can present with a wide range of signs and symptoms based on the location of the lesions and other factors such as disease duration.[4]
The prevalence of MS and its forms of presentation differ between nations and even between different geographical regions in a nation. It has been shown that seizure and epilepsy are more common in MS cases than that in the general population. Previous registry studies showed a higher incidence of seizure in MS cases.[5],[6]
The prognosis of a single seizure/epilepsy is important in patients with MS. Studies show that drug-resistant seizure/epilepsy is less common in MS, while status epilepticus is more frequent.[7],[8],[9],[10] Magnetic resonance imaging (MRI) findings showed a positive correlation between cortico-subcortical lesions and presentation of seizure/epilepsy.[11],[12]
As seizure and epilepsy are among the prevalent symptoms of MS, it's important to study them. The prevalence of seizure/epilepsy has been reported variously in previous studies. So, we designed this systematic review to estimate the pooled prevalence of seizure and epilepsy in patients with MS.
| Methods | | |
Literature search
We searched PubMed, Scopus, EMBASE, Web of Science, google scholar and gray literature including references from identified studies, and conference abstracts published up to October 2019.
Inclusion criteria
The inclusion criteria were cross-sectional studies evaluating the prevalence of seizure or epilepsy in patients with MS, published in the English language.
Data search and extraction
The search strategy included the MeSH terms and text words as ((Epilepsies OR Seizure Disorder OR Seizure Disorders OR Awakening Epilepsy OR Epilepsy, Awakening OR Epilepsy, Cryptogenic OR Cryptogenic Epilepsies OR Cryptogenic Epilepsy OR Epilepsies, Cryptogenic OR epilepsy OR seizure) AND (Multiple Sclerosis OR Sclerosis, Multiple) OR Sclerosis, Disseminated) OR Disseminated Sclerosis) OR MS (Multiple Sclerosis)) OR Multiple Sclerosis, Acute Fulminating).
Two researchers independently assessed the resulted articles. In the case of discrepancy, a third researcher solved the problem. Data on the total number of participants, first author, publication year, country, mean patient age at MS onset, and a number of cases with seizure or epilepsy were extracted from the included studies.
Statistical analysis
All statistical analyses were performed using STATA (Version 13.0; Stata Corp LP, College Station, TX, USA). We used the inverse-variance approach with a random-effects model. Inconsistency (I2) was calculated to estimate heterogeneity. Meta-regression analysis was conducted considering “continent” as a source of heterogeneity for the prevalence of epilepsy.
| Results | | |
The literature search resulted in 4860 articles, but 2267 were duplicates and were eliminated. From 2593 remaining articles, 2554 were either not cross-sectional studies or not published in English. Thus, 39 articles were included for final analysis [Figure 1], 9 of which were conference abstracts [Table 1].
The included studies were published between 1972 and 2019 in Asia (n = 5), Europe (n = 29), and America (n = 5). The sample sizes ranged from 63 to 15810.
The pooled prevalence of seizure in MS cases was 2%, 95% confidence interval (CI)(1%-3%) (I2 = 91.8%, P < 0.001) [Figure 2].
The pooled prevalence of epilepsy in MS cases was 3%, 95% CI (2%-4%) (I2 = 92.9%, P < 0.001) [Figure 3].
The pooled prevalence of epilepsy in Asia, Europe, and America was 6%, 3%, and 3%, respectively [Figure 4]. The level of heterogeneity decreased after subgroup analysis in Asian and American subgroups. However, Meta-regression analysis showed continent is not a source of heterogeneity (coefficient = -0.007, P = 0.6). | Figure 4: The pooled prevalence of epilepsy in multiple sclerosis cases in each continent
Click here to view |
| Discussion | | |
To our knowledge, this is the first systematic review and meta-analysis on the prevalence of epilepsy in MS patients. Our results showed that the pooled prevalence of seizure and epilepsy was 2% and 3%, respectively. Subgroup analysis showed different prevalence rates of epilepsy between continents, while according to advance analysis, the continent was not a source of heterogeneity.
In a previous Norwegian study, Benjaminsen et al. found that the prevalence of focal epilepsy in MS cases was 3.2%, which was 4.5-fold higher than that in the general population.[9] According to their results, active epilepsy increased the risk of conversion from RRMS to SPMS. Engelsen et al. reported the prevalence of epilepsy as 4% in MS patients, which was near four times higher than the prevalence reported in the general population.[22] In a study conducted by Eriksson in Sweden, the prevalence of epilepsy in MS individuals was found as 3.5%, while in the general population, it was reported as 0.53%-0.64%.[45] In another Swedish study by Mahamud et al., the 10-year risk of epilepsy was 51.4% in MS patients and 41.3% in controls. The risk for SPMS and RRMS cases was 60% and 46%, respectively.[31] Krokki et al. indicated epilepsy as the most prevalent comorbidity in MS, which was found in 4.7% of 491 definite MS patients.[27] Langenbruch et al. assessed 4078 MS patients and reported seizure in 1.5% and epilepsy in 0.9%.[28] In a Japanese study conducted by Nakano et al., the prevalence of epilepsy in MS patients was twice the prevalence in neuromyelitis optica patients.[35]
The cause of seizure in MS is not clear, however cortical and juxtacortical inammation, demyelination, and atrophy are considered to play a role in the development of seizures/epilepsies in MS.[46],[47]
Seizure or epilepsy could occur at any time during the disease. All types of seizures have been reported in MS.[32] Some researchers believe the most common type of seizure in MS is focal seizure (FS) followed by secondary generalization, while others consider primary generalized tonic-clonic seizures as the most frequent type.[7],[42],[48],[49] Martínez-Lapiscina et al. reported epilepsy in 3% of their MS cases and focal seizures in 80%.[32]
Some authors believe that epilepsies are common in relapsing-remitting form of MS, but there are controversies over it.[30],[42] One reason for seizures in MS patients might be the locations of MRI lesions. Some authors believe lesions extended to the cortex are the risk factors of seizures in MS. Calabrese et al. reported that intra-cortical lesions are five times more prevalent in RRMS patients with seizures than in those without it.[46] Another study on MRI examinations confirmed a higher number of cortical and juxtacortical lesions in MS individuals who experienced seizure compared to other MS patients. This study also showed that cortical and juxtacortical lesions were independent predictors of seizures, by controlling the total number of lesions and brain atrophy.[32] More intensive inflammation was reported in the cortex of MS cases with epilepsy than in those without epilepsy.[46] Waxman suggested the role of demyelination in the sodium channel gene activation, which would result in hyperexcitability.[50]
Seizure/epilepsy can be the first symptom of MS, the incidence rate of which increase with the longer duration of the disease or the higher number of lesions.[9] However, no relationship has been found between the severity of MS and epilepsy.[26],[34]
The prognosis of seizure in MS patients is highly controversial.[42],[48],[49] Administration of antiepileptic medications is recommended to prevent new seizures and status epilepticus.[22]
| Conclusions | | |
The result of this systematic review shows that in MS patients, the pooled prevalence of seizure and epilepsy is 2% and 3%, respectively.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Ghajarzadeh M, Keshtkar AA, Azimi A, Sahraian MA, Mohammadifar M, Ramagopalan SV. The effect of vitamin D Supplements on clinical and para-clinical outcomes in patients with multiple sclerosis: Protocol for a systematic review. JMIR Res Protoc 2019;8:e12045.  |
| 2. | Azimi A, Hanaei S, Sahraian MA, Mohammadifar M, Ramagopalan SV, Ghajarzadeh M. Incidence of seroconversion and sero-reversion in patients with multiple sclerosis (MS) who had been treated with natalizumab: A systematic review and meta-analysis. J Clin Neurosci 2020;71:129-134. |
| 3. | Ghajarzadeh M, Mahsa O, Sauraian MA, Moghadasi AN, Azimi A. Emotional intelligence (EI) of patients with multiple sclerosis (MS). Iran J Public Health 2014;43:1550-6. |
| 4. | Cheng M-Y, Wai Y-Y, Ro L-S, Wu T. Seizures and multiple sclerosis in Chinese patients: A clinical and magnetic resonance imaging study. Epilepsy Res 2012;101:166-73. |
| 5. | Allen AN, Seminog OO, Goldacre MJ. Association between multiple sclerosis and epilepsy: Large population-based record-linkage studies. BMC Neurol 2013;13:189. |
| 6. | Burman J, Zelano J. Epilepsy in multiple sclerosis: A nationwide population-based register study. Neurology 2017;89:2462-8. |
| 7. | Catenoix H, Marignier R, Ritleng C, Dufour M, Mauguière F, Confavreux C, et al. Multiple sclerosis and epileptic seizures. Mult Scler J 2011;17:96-102. |
| 8. | Lund C, Nakken K, Edland A, Celius E. Multiple sclerosis and seizures: Incidence and prevalence over 40 years. Acta Neurol Scand 2014;130:368-73. |
| 9. | Benjaminsen E, Myhr K-M, Alstadhaug KB. The prevalence and characteristics of epilepsy in patients with multiple sclerosis in Nordland county, Norway. Seizure 2017;52:131-5. |
| 10. | Dagiasi I, Vall V, Kumlien E, Burman J, Zelano J. Treatment of epilepsy in multiple sclerosis. Seizure 2018;58:47-51. |
| 11. | Thompson A, Kermode A, Moseley I, MacManus D, McDonald W. Seizures due to multiple sclerosis: Seven patients with MRI correlations. J Neurol Neurosurg Psychiatry 1993;56:1317-20. |
| 12. | Moreau T, Sochurkova D, Lemesle M, Madinier G, Billiar T, Giroud M, et al. Epilepsy in patients with multiple sclerosis: Radiological-clinical correlations. Epilepsia 1998;39:893-6. |
| 13. | Averianova L, Shakirzianova S, Khaibullin T, Khabirov F, Granatov E, Babicheva N. Epilepsy in multiple sclerosis (MS): Clinical, electroencephalographic (EEG) and magnetic resonance imaging (MRI) characteristics. Multiple Sclerosis J 2017;23:735. |
| 14. | Basso P, Ghezzi A, Montanini R, Zibetti A, Marforio S, Zaffaroni M, et al. Seizures in multiple sclerosis patients. Bollettino-Lega Italiana contro l'Epilessia 1989:215-7. |
| 15. | Biserni P, Fini M, Cattaneo A, Capitanio L, Mendozzi L, Pugnetti L. Epilepsy in multiple sclerosis. Bollettino-Lega Italiana contro l'Epilessia 1993:253-5. |
| 16. | Coletti Moja M, Milano E, Gasverde S, Melis F, Malucchi S, Bottero R, et al. Epilepsy and multiple sclerosis. Bollettino-Lega Italiana contro l'Epilessia 2003:323-5. |
| 17. | Howell OW, Nicholas R, Gveric D, Rees MI, Roncaroli F, Reynolds R. The risk of seizures in progressive multiple sclerosis. Epilepsia 2012;53:24-5. |
| 18. | Kruja J, Mijo S. Seizures and multiple sclerosis. Epilepsia 2009;50:167-8. |
| 19. | Passarell MA, Otero-Romero S, Bufill E, Lopez-Jimenez T, Deniel J, Sastre-Garriga J, et al. Excess of neurological and psychiatric comorbidity in multiple sclerosis patients as compared to the general population in Catalonia, Spain. Mult Scler J 2017;23:169. |
| 20. | Petre VR, Buraga I, Baetu C, Enachi AM, Lungu V, Amarandei M. Epilepsy in multiple sclerosis. Eur J Neurol 2016;23:504. |
| 21. | Cendrowski W, Majkowski J. Epilepsy in multiple sclerosis. J Neurol Sci 1972;17:389-98. |
| 22. | Engelsen BA, Gronning M. Epileptic seizures in patients with multiple sclerosis. Is the prognosis of epilepsy underestimated? Seizure 1997;6:377-82. |
| 23. | Eriksson M, Ben-Menachem E, Andersen O. Epileptic seizures, cranial neuralgias and paroxysmal symptoms in remitting and progressive multiple sclerosis. Mult Scler (Houndmills, Basingstoke, England) 2002;8:495-9. |
| 24. | Etemadifar M, Abtahi SH, Roomizadeh P. Epileptic seizures in multiple sclerosis: A population-based survey in Iran. Acta Neurol Belg 2013;113:271-8. |
| 25. | Etemadifar M, Abtahi SH, Tabrizi N. Epileptic seizures in early-onset multiple sclerosis. Arch Iran Med 2012;15:381-3. |
| 26. | Kinnunen E, Wikstrom J. Prevalence and prognosis of epilepsy in patients with multiple sclerosis. Epilepsia 1986;27:729-33. |
| 27. | Krökki O, Bloigu R, Ansakorpi H, Reunanen M, Remes AM. Neurological comorbidity and survival in multiple sclerosis. Mult Scler Relat Disord 2014;3:72-7. |
| 28. | Langenbruch L, Krämer J, Güler S, Möddel G, Geβner S, Melzer N, et al. Seizures and epilepsy in multiple sclerosis: Epidemiology and prognosis in a large tertiary referral center. J Neurol 2019;266:1789-95. |
| 29. | Laroni A, Signori A, Maniscalco GT, Lanzillo R, Russo CV, Binello E, et al. Assessing association of comorbidities with treatment choice and persistence in MS: A real-life multicenter study. Neurology 2017;89:2222-9. |
| 30. | Martínez-Juárez IE, López-Meza E, González-Aragón MdCF, Ramírez-Bermúdez J, Corona T. Epilepsy and multiple sclerosis: Increased risk among progressive forms. Epilepsy Res 2009;84:250-3. |
| 31. | Mahamud Z, Burman J, Zelano J. Risk of epilepsy after a single seizure in multiple sclerosis. Eur J Neurol 2018;25:854-60. |
| 32. | Martinez-Lapiscina EH, Ayuso T, Lacruz F, Gurtubay IG, Soriano G, Otano M, et al. Cortico-juxtacortical involvement increases risk of epileptic seizures in multiple sclerosis. Acta Neurol Scand 2013;128:24-31. |
| 33. | Nyquist PA, Cascino GD, Rodriguez M. Seizures in patients with multiple sclerosis seen at Mayo Clinic, Rochester, Minn, 1990-1998. Mayo Clin Proc 2001;76:983-6. |
| 34. | Ghezzi A, Montanini R, Basso P, Zaffaroni M, Massimo E, Cazzullo C. Epilepsy in multiple sclerosis. Eur Neurol 1990;30:218-23. |
| 35. | Nakano H, Tanaka M, Kinoshita M, Tahara M, Matsui M, Tanaka K, et al. Epileptic seizures in Japanese patients with multiple sclerosis and neuromyelitis optica. Epilepsy Res 2013;104:175-80. |
| 36. | Nicoletti A, Sofia V, Biondi R, Fermo SL, Reggio E, Patti F, et al. Epilepsy and multiple sclerosis in Sicily: A population-based study. Epilepsia 2003;44:1445-8. |
| 37. | Olafsson E, Benedikz J, Hauser WA. Risk of epilepsy in patients with multiple sclerosis: A population-based study in Iceland. Epilepsia 1999;40:745-7. |
| 38. | Shaygannejad V, Ashtari F, Zare M, Ghasemi M, Norouzi R, Maghzi H. Seizure characteristics in multiple sclerosis patients. J Res Med Sci 2013;18(Suppl 1):S74-7. |
| 39. | Uribe R, Ciampi E, Suarez F, Godoy J, Cárcamo C. Prevalence of epilepsy in a cohort of patients with multiple sclerosis. Epilepsia 2013;54:279. |
| 40. | Schorner A, Weissert R. Patients with epileptic seizures and multiple sclerosis in a multiple sclerosis center in Southern Germany between 2003-2015. Front Neurol 2019;10:613. |
| 41. | Viveiros CD, Alvarenga RM. Prevalence of epilepsy in a case series of multiple sclerosis patients. Arq Neuropsiquiatr 2010;68:731-6. |
| 42. | Striano P, Orefice G, Brescia Morra V, Boccella P, Sarappa C, Lanzillo R, et al. Epileptic seizures in multiple sclerosis: Clinical and EEG correlations. Neurol Sci 2003;24:322-8. |
| 43. | Sokic DV, Stojsavljevic N, Drulovic J, Dujmovic I, Mesaroš S, Ercegovac M, et al. Seizures in multiple sclerosis. Epilepsia 2001;42:72-9. |
| 44. | Simpson RJ, McLean G, Guthrie B, Mair F, Mercer SW. Physical and mental health comorbidity is common in people with multiple sclerosis: Nationally representative cross-sectional population database analysis. BMC Neurol 2014;14:128. |
| 45. | Forsgren L. Prevalence of epilepsy in adults in northern Sweden. Epilepsia 1992;33:450-8. |
| 46. | Calabrese M, De Stefano N, Atzori M, Bernardi V, Mattisi I, Barachino L, et al. Extensive cortical inflammation is associated with epilepsy in multiple sclerosis. J Neurol 2008;255:581-6. |
| 47. | Calabrese M, Grossi P, Favaretto A, Romualdi C, Atzori M, Rinaldi F, et al. Cortical pathology in multiple sclerosis patients with epilepsy: A 3 year longitudinal study. J Neurol Neurosurg Psychiatry 2012;83:49-54. |
| 48. | Kelley BJ, Rodriguez M. Seizures in patients with multiple sclerosis. CNS Drugs 2009;23:805-15. |
| 49. | Koch M, Uyttenboogaart M, Polman S, De Keyser J. Seizures in multiple sclerosis. Epilepsia 2008;49:948-53. |
| 50. | Waxman SG. Acquired channelopathies in nerve injury and MS. Neurology 2001;56:1621-7. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1]
|
Search Pubmed for