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Mitochondrial epilepsy: a cross-sectional nationwide Italian survey

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Abstract

Many aspects of epilepsy in mitochondrial disorders (MDs) need to be further clarified. To this aim, we explored retrospectively a cohort of individuals with MDs querying the “Nationwide Italian Collaborative Network of Mitochondrial Diseases” (NICNMD) database (1467 patients included since 2010 to December 2016). We collected information on age at epilepsy onset, seizure type and frequency, genetic findings, and antiepileptic drugs (AEDs). At the time of our survey, 147/1467 (10%) patients in the NICNMD database had epilepsy. Complete information was available only for 98 patients, 52 males and 46 females, aged 5–92 years (mean age 40.4 ± 18.4; 14/98 children/teenagers and 84 adults). Epilepsy was the presenting feature of MD in 46/98 (47%) individuals, with onset at a median age of 19 years (range, 0.2–68; < 3 years in 14/97 (14%), 3–19 years in 36/97 (37%), > 19 years in 47/97 (49%)). Moreover, 91/98 patients (93%) displayed multiple seizures, with daily or weekly frequency in 25/91 (28%). Interictal EEG was abnormal in 70/78 (90%) patients, displaying abnormal background (47/70; 67%) and/or interictal paroxysms (53/70; 76%). Eighty of 90 patients (89%) displayed a 50–100% reduction of seizures on AEDs; levetiracetam was the most commonly used. Forty-one patients (42%) carried the m.3243A>G mutation, 16 (16%) the m.8344A>G, and 9 (9%) nuclear DNA (nDNA) mutations. Individuals with early-onset seizures mainly carried nDNA mutations and had a more severe epilepsy phenotype, higher seizure frequency, and disorganized background EEG activity. A better definition of epilepsy in MDs may foster the diagnostic workup, management, and treatment of affected patients, and allow more homogeneous patient stratification.

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Acknowledgments

We are indebted to Dr. Catherine J. Wrenn for the expert editing of the manuscript and critical advice.

Funding

This study received financial support from the Italian Ministry of Health-Ricerca Corrente, MITO-NEXT, Mit-OMICS (to FMS) and 5X1000 (to FS), Fondazione Telethon (Grant numbers GUP09004 and GSP16001), and the patients’ association MITOCON, which also provided the web-platform assistance.

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Author notes

  1. Chiara Ticci and Federico Sicca contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Chiara Ticci, Gabriele Siciliano, Costanza Simoncini & Michelangelo Mancuso

  2. IRCCS Fondazione Stella Maris, Pisa, Italy

    Chiara Ticci, Federico Sicca, Anna Rubegni & Filippo M. Santorelli

  3. Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

    Anna Ardissone & Isabella Moroni

  4. Bambino Gesù Hospital IRCCS, Rome, Italy

    Enrico Bertini, Daria Diodato & Diego Martinelli

  5. IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy

    Valerio Carelli, Lidia Di Vito & Chiara La Morgia

  6. Neurological Clinic, University Hospital Spedali Civili, Brescia, Italy

    Massimiliano Filosto

  7. Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

    Costanza Lamperti & Lorenzo Peverelli

  8. Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy

    Olimpia Musumeci & Antonio Toscano

  9. Unit of Neurology, San Luca Hospital, Lucca, Italy

    Daniele Orsucci

  10. Neurological Clinic, University of Verona, Verona, Italy

    Elia Pancheri & Paola Tonin

  11. UOC Neurofisiopatologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Guido Primiano & Serenella Servidei

Authors
  1. Chiara Ticci
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  2. Federico Sicca
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  3. Anna Ardissone
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  4. Enrico Bertini
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  13. Olimpia Musumeci
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  16. Lorenzo Peverelli
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  25. Filippo M. Santorelli
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Corresponding author

Correspondence to Filippo M. Santorelli.

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This study was conducted in accordance with the standards and approved by the ethics committees of all the centers involved in the study; these centers obtained written informed consent from all participating patients or their legal guardians, in accordance with the ethical standards of the 1964 Declaration of Helsinki.

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The authors declare that they have no conflict of interest.

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Ticci, C., Sicca, F., Ardissone, A. et al. Mitochondrial epilepsy: a cross-sectional nationwide Italian survey. Neurogenetics 21, 87–96 (2020). https://doi.org/10.1007/s10048-019-00601-5

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  • DOI: https://doi.org/10.1007/s10048-019-00601-5

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