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The phenotypic spectrum of epilepsy associated with periventricular nodular heterotopia

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Abstract

Background

Periventricular nodular heterotopia (PVNH) is a congenital brain malformation often associated with seizures. We aimed to clarify the spectrum of epilepsy phenotypes in PVNH and the significance of specific brain malformation patterns.

Methods

In this retrospective cohort study, we recruited people with PVNH and a history of seizures, and collected data via medical record review and a standardized questionnaire.

Results

One hundred individuals were included, aged 1 month to 61 years. Mean seizure onset age was 7.9 years. Ten patients had a self-limited epilepsy course and 35 more were pharmacoresponsive. Fifty-five had ongoing seizures, of whom 23 met criteria for drug resistance. Patients were subdivided as follows: isolated PVNH (“PVNH-Only”) single nodule (18) or multiple nodules (21) and PVNH with additional brain malformations (“PVNH-Plus”) single nodule (8) or multiple nodules (53). Of PVNH-Only single nodule, none had drug-resistant seizures. Amongst PVNH-Plus, 55% with multiple unilateral nodules were pharmacoresponsive, compared to only 21% with bilateral nodules. PVNH-Plus with bilateral nodules demonstrated the highest proportion of drug resistance (39%). A review of genetic testing results revealed eight patients with pathogenic or likely pathogenic single-gene variants, two of which were FLNA. Five had copy number variants, two of which were pathogenic.

Conclusions

The spectrum of epilepsy phenotypes in PVNH is broad, and seizure patterns are variable; however, epilepsy course may be predicted to an extent by the pattern of malformation. Overall, drug-resistant epilepsy occurs in approximately one quarter of affected individuals. When identified, genetic etiologies are very heterogeneous.

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Data availability

Full data are available from the corresponding author upon request.

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Acknowledgements

The authors would like to thank all who participated in this research project. We thank PVNH Support & Awareness who helped to publicize this study. This research was funded by the Fonds de Recherche du Québec – Santé (282228, 295639) and the Research Institute of the McGill University Health Centre.

Funding

Supported by Research Institute of the McGill University Health Centre and Fonds de Recherches du Québec – Santé.

Author information

Authors and Affiliations

  1. Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada

    Karina Paliotti

  2. Research Institute of the McGill University Health Centre, Montreal, QC, Canada

    Christelle Dassi, Saoussen Berrahmoune, Myriam Srour & Kenneth A. Myers

  3. Pediatric Neurology Department, Sant Joan de Déu Barcelona Children’s Hospital, Sant Joan de Déu Research Institute, Member of the ERN EpiCARE, Barcelona, Spain

    Marlin Liz Bejaran, Carlos Eduardo Valera Davila, Ariadna Borràs Martinez & Maria Carme Fons Estupiñà

  4. Epilepsy Center, Reference Center for Rare and Complex Epilepsies-EpiCARE, IRCCS Istituto Gaslini, Genoa, Italy

    Maria Margherita Mancardi

  5. Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Gaslini, University of Genoa, Genoa, Italy

    Antonella Riva

  6. Neuroradiology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy

    Thea Giacomini & Mariasevina Severino

  7. Child Neuropsychiatry and Neurorehabilitation Department, Scientific Institute Eugenio Medea, La Nostra Famiglia, Lecco, Italy

    Romina Romaniello

  8. Division of Neurology, Department of Pediatrics, Montreal Children’s Hospital, McGill University Health Centre, MUHC Glen Site, 1001 Décarie Blvd, Montreal, QC, H4A 3J1, Canada

    Myriam Srour & Kenneth A. Myers

  9. Department of Neurology and Neurosurgery, McGill University Health Centre, Montreal, QC, Canada

    François Dubeau, Myriam Srour & Kenneth A. Myers

Authors
  1. Karina Paliotti
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  2. Christelle Dassi
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  7. Maria Carme Fons Estupiñà
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  8. Maria Margherita Mancardi
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  15. Kenneth A. Myers
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Contributions

KP: conceptualization (supporting); investigation (lead); data curation (lead); formal analysis (lead); visualization (lead); writing—original draft (lead); writing—review and editing (supporting). CD: data curation (supporting); resources (supporting). SB: project administration (lead); resources (lead). MLB: investigation (supporting); data curation (supporting). CEVD: data curation (supporting). ABM: data curation (supporting). MCFE: data curation (supporting). MMM: data curation (supporting). AR: investigation (supporting); data curation (supporting). TG: investigation (supporting); data curation (supporting). MS: data curation (supporting); writing—review and editing (supporting). RR: data curation (supporting). FD: data curation (supporting). MS: data curation (supporting). KAM: conceptualization (lead); funding acquisition (lead); supervision (lead); validation (lead); writing—review and editing (lead).

Corresponding author

Correspondence to Kenneth A. Myers.

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Conflict of interest

Dr. Myers holds or has held research funding from Savoy Foundation, Dravet Canada, Research Institute of the McGill University Health Centre, Citizens United for Research in Epilepsy (439534), Koolen-de Vries Foundation, Liam Foundation, and Fonds de Recherches du Québec – Santé; he is also a site principal investigator for studies by LivaNova and Ultragenyx. The other authors report no conflicts of interest.

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Paliotti, K., Dassi, C., Berrahmoune, S. et al. The phenotypic spectrum of epilepsy associated with periventricular nodular heterotopia. J Neurol 270, 3934–3945 (2023). https://doi.org/10.1007/s00415-023-11724-z

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  • DOI: https://doi.org/10.1007/s00415-023-11724-z

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