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Pilomotor seizures in autoimmune limbic encephalitis: description of two GAD65 antibodies- related cases and literature review

  • Author Footnotes
    1 These authors contributed equally to this work.
    Federica Pondrelli
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Dipartimento di Scienze Biomediche e Neuromotorie, Università Degli Studi di Bologna, Via Altura, 3, Bologna, Italy
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Maria Pia Giannoccaro
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Dipartimento di Scienze Biomediche e Neuromotorie, Università Degli Studi di Bologna, Via Altura, 3, Bologna, Italy

    IRCCS Istituto delle Scienze Neurologiche di Bologna, Full Member of the ERN EpiCARE, Bologna, Italy
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  • Francesca Bisulli
    Affiliations
    Dipartimento di Scienze Biomediche e Neuromotorie, Università Degli Studi di Bologna, Via Altura, 3, Bologna, Italy

    IRCCS Istituto delle Scienze Neurologiche di Bologna, Full Member of the ERN EpiCARE, Bologna, Italy
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  • Lorenzo Ferri
    Affiliations
    Dipartimento di Scienze Biomediche e Neuromotorie, Università Degli Studi di Bologna, Via Altura, 3, Bologna, Italy
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  • Veronica Menghi
    Affiliations
    Dipartimento di Scienze Biomediche e Neuromotorie, Università Degli Studi di Bologna, Via Altura, 3, Bologna, Italy
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  • Barbara Mostacci
    Affiliations
    IRCCS Istituto delle Scienze Neurologiche di Bologna, Full Member of the ERN EpiCARE, Bologna, Italy
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  • Patrizia Avoni
    Affiliations
    Dipartimento di Scienze Biomediche e Neuromotorie, Università Degli Studi di Bologna, Via Altura, 3, Bologna, Italy

    IRCCS Istituto delle Scienze Neurologiche di Bologna, Full Member of the ERN EpiCARE, Bologna, Italy
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  • Rocco Liguori
    Affiliations
    Dipartimento di Scienze Biomediche e Neuromotorie, Università Degli Studi di Bologna, Via Altura, 3, Bologna, Italy

    IRCCS Istituto delle Scienze Neurologiche di Bologna, Full Member of the ERN EpiCARE, Bologna, Italy
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  • Paolo Tinuper
    Affiliations
    Dipartimento di Scienze Biomediche e Neuromotorie, Università Degli Studi di Bologna, Via Altura, 3, Bologna, Italy

    IRCCS Istituto delle Scienze Neurologiche di Bologna, Full Member of the ERN EpiCARE, Bologna, Italy
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  • Laura Licchetta
    Correspondence
    Corresponding author.
    Affiliations
    IRCCS Istituto delle Scienze Neurologiche di Bologna, Full Member of the ERN EpiCARE, Bologna, Italy
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  • Author Footnotes
    1 These authors contributed equally to this work.

      Highlights

      • The prevalence of pilomotor seizures in patients affected by limbic encephalitis may be higher than expected.
      • LGI1 and GAD65 emerged as the most frequently associated antibodies to ictal piloerection.
      • SSR recording may help detecting ictal piloerection.

      Abstract

      Background

      Ictal piloerection (IP) is a rare manifestation of focal epilepsy. Autoimmune limbic encephalitis (LE) and malignant brain tumours are the most frequent recognized aetiologies.

      Methods

      We selected all patients diagnosed with LE in our Institute from 2004 to 2020 and manifesting with IP. We performed a literature review on LE patients presenting IP.

      Results

      Of 15 patients diagnosed with LE (13.3%), two manifested IP as prominent ictal feature. One of them also had stiff-limb syndrome. Video-EEG documented ictal discharges from the right temporal regions with concomitant sympathetic skin response (SSR) recording. Antibody testing showed elevated serum and CSF titres of GAD65 antibodies (Ab), in both cases. Despite a combination of several anti-seizure medications and first- and second-line immunotherapy, they showed a poor clinical outcome after 2 and 9 years of follow-up, respectively. The literature review yielded 13 papers reporting 26 LE cases with IP. LGI1 Ab were the most frequently associated (73.1%) followed by VGKC-complex (7.7%), GAD65 (7.7%), NMDAr (3.8%), Ma2 (3.8%) and Hu (3.8%) Ab. Cases with LGI1 Ab showed a good response to immunotherapy.

      Discussion and conclusion

      The prevalence of IP in our LE cohort was of 13.3%, higher than expected. According to the literature review, most cases were associated with LGI1 Ab and showed a good response to immunotherapy. With the contribution of our cases, GAD65 emerged as the second most frequently detected Ab, showing a poor outcome. Our findings widen the spectrum of IP-associated Ab, with the respective prognostic implications.

      Keywords

      Abbreviations:

      IP (Ictal piloerection), LE (Limbic encephalitis), Ab (Antibodies)
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