Neurological Sciences

, Volume 38, Issue 3, pp 399–406 | Cite as

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

  • Sara Gasparini
  • Edoardo Ferlazzo
  • Michele Ascoli
  • Chiara Sueri
  • Vittoria Cianci
  • Concetta Russo
  • Laura Rosa Pisani
  • Pasquale Striano
  • Maurizio Elia
  • Ettore Beghi
  • Carmela Colica
  • Umberto AgugliaEmail author
  • On behalf of the Epilepsy Study Group of the Italian Neurological Society
Review Article


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 = −5.42 years, 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.


Multiple sclerosis Epilepsy Meta-analysis Age Cortical lesion 


Compliance with ethical standards

Conflict of interest

Dr. Beghi reports grants from Italian Ministry of Health, during the conduct of the study; personal fees from Viropharma, grants from UCB-Pharma, grants from Italian Drug Agency (AIFA), personal fees from Viropharma, grants from Italian Ministry of Health, grants from EISAI, grants from American ALS Association, grants from Borgonovo Foundation, outside the submitted work. All other authors have no conflict of interest to declare.


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Copyright information

© Springer-Verlag Italia 2016

Authors and Affiliations

  • Sara Gasparini
    • 1
    • 2
  • Edoardo Ferlazzo
    • 1
    • 2
  • Michele Ascoli
    • 1
    • 2
  • Chiara Sueri
    • 2
  • Vittoria Cianci
    • 2
  • Concetta Russo
    • 2
  • Laura Rosa Pisani
    • 3
  • Pasquale Striano
    • 4
  • Maurizio Elia
    • 5
  • Ettore Beghi
    • 6
  • Carmela Colica
    • 7
  • Umberto Aguglia
    • 1
    • 2
    Email author
  • On behalf of the Epilepsy Study Group of the Italian Neurological Society
  1. 1.Department of Medical and Surgical SciencesMagna Graecia University of CatanzaroCatanzaroItaly
  2. 2.Regional Epilepsy CentreBianchi-Melacrino-Morelli HospitalReggio CalabriaItaly
  3. 3.IRCCS Centro Neurolesi Bonino-PulejoMessinaItaly
  4. 4.Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, G. Gaslini InstituteUniversity of GenovaGenoaItaly
  5. 5.Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS)TroinaItaly
  6. 6.Laboratory of Neurological DisordersIRCCS-Istituto di Ricerche Farmacologiche ‘‘Mario Negri’’MilanItaly
  7. 7.Institute of Bioimaging and Molecular PhysiologyNational Research CouncilCatanzaroItaly

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