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

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Abstract

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.

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Authors and Affiliations

  1. Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Viale Europa, Catanzaro, Italy

    Sara Gasparini, Edoardo Ferlazzo, Michele Ascoli & Umberto Aguglia

  2. Regional Epilepsy Centre, Bianchi-Melacrino-Morelli Hospital, Via Melacrino, Reggio Calabria, Italy

    Sara Gasparini, Edoardo Ferlazzo, Michele Ascoli, Chiara Sueri, Vittoria Cianci, Concetta Russo & Umberto Aguglia

  3. IRCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy

    Laura Rosa Pisani

  4. Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, G. Gaslini Institute, University of Genova, Via Gaslini 5, Genoa, Italy

    Pasquale Striano

  5. Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Via Conte Ruggero 73, Troina, EN, Italy

    Maurizio Elia

  6. Laboratory of Neurological Disorders, IRCCS-Istituto di Ricerche Farmacologiche ‘‘Mario Negri’’, Via La Masa 19, Milan, Italy

    Ettore Beghi

  7. Institute of Bioimaging and Molecular Physiology, National Research Council, Viale Europa, Catanzaro, Italy

    Carmela Colica

Authors
  1. Sara Gasparini
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  2. Edoardo Ferlazzo
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  3. Michele Ascoli
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  4. Chiara Sueri
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  5. Vittoria Cianci
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  6. Concetta Russo
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  7. Laura Rosa Pisani
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  8. Pasquale Striano
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  9. Maurizio Elia
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  10. Ettore Beghi
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  11. Carmela Colica
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  12. Umberto Aguglia
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Consortia

On behalf of the Epilepsy Study Group of the Italian Neurological Society

  • V. Belcastro
  • , A. Bianchi
  • , S. Calabrò
  • , F. De Falco
  • , G. De Maria
  • , C. A. Galimberti
  • , A. Gambardella
  • , A. Iudice
  • , A. Labate
  • , A. La Neve
  • , E. Le Piane
  • , F. Monti
  • , L. Mumoli
  • , F. Paladin
  • , F. Pisani
  • , V. Pizza
  • , L. Provinciali
  • , V. Sofia
  • , L. M. Specchio
  • , N. Specchio
  • , S. Striano
  • , F. Villani
  •  & G. Zaccara

Corresponding author

Correspondence to Umberto Aguglia.

Ethics declarations

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.

Additional information

See Appendix A for the complete list of contributors.

Appendices

Appendix A: Members of the Epilepsy Study Group of the Italian Neurological Society

Belcastro V, Bianchi A, Calabrò S, De Falco F, De Maria G, Galimberti CA, Gambardella A, Iudice A, Labate A, La Neve A, Le Piane E, Monti F, Mumoli L, Paladin F, Pisani F, Pizza V, Provinciali L, Sofia V, Specchio LM, Specchio N, Striano S, Villani F, Zaccara G.

Appendix B. Search strategies

PUBMED: Multiple Sclerosis [Mesh] AND (Epilepsy [Mesh] OR Seizures [Mesh]).

SCOPUS:

  1. 1.

    “Epilepsy” AND “multiple sclerosis”

  2. 2.

    “Seizures” AND “multiple sclerosis”.

GOOGLE SCHOLAR:

  1. 1.

    allintitle: multiple sclerosis and epilepsy

  2. 2.

    allintitle: multiple sclerosis and seizures.

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Gasparini, S., Ferlazzo, E., Ascoli, M. et al. Risk factors for unprovoked epileptic seizures in multiple sclerosis: a systematic review and meta-analysis. Neurol Sci 38, 399–406 (2017). https://doi.org/10.1007/s10072-016-2803-7

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  • DOI: https://doi.org/10.1007/s10072-016-2803-7

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