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Response to: Management of Seizures and Epilepsy in Patients with Autoimmune Encephalitis

Published online by Cambridge University Press:  29 April 2024

Chris Hahn*
Affiliation:
Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
Jennifer A. McCombe
Affiliation:
Division of Neurology, University of Alberta, Edmonton, AB, Canada
Adrian Budhram
Affiliation:
Department of Pathology and Laboratory Medicine, Western University, London Health Sciences Centre, London, ON, Canada Clinical Neurological Sciences, London Health Sciences Centre, London, ON, Canada
*
Corresponding author: C. Hahn; Email: [email protected]
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Abstract

Type
Letters to the Editor: Published Article
Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of Canadian Neurological Sciences Federation

Dear Editor,

We thank Dr Burneo for his interest in our recent publication, Reference Hahn, Budhram and Alikhani1 as well as for his comments. He correctly notes that these Canadian consensus guidelines focus on the acute management of autoimmune encephalitis, prompt treatment of which may reduce the likelihood of developing irreversible structural injury that causes an enduring seizure predisposition (i.e. autoimmune encephalitis-associated epilepsy, or AEAE). It is for this reason that, while we wholeheartedly agree with its importance as part of ongoing care for patients with autoimmune encephalitis, the long-term management of AEAE is not extensively discussed in our publication. We also fully agree with the importance of considering the availability not only of anti-seizure medications (ASMs) but also other symptomatic and disease-modifying therapies for autoimmune encephalitis in different practice settings around the world; however, this is similarly outside the scope of these Canadian-focused guidelines.

Patients with neural antibodies against extracellular targets (e.g. anti-NMDAR, LGI1, CASPR2, GABA(B)R) frequently attain seizure freedom following adequate immunotherapy, indicating acute symptomatic seizures secondary to autoimmune encephalitis rather than AEAE. Reference de Bruijn, van Sonderen and van Coevorden-Hameete2,Reference Liu, Guo and Lin3 Dr Burneo raises the important point that, particularly among patients harbouring neural antibodies against intracellular targets (e.g. most high-risk paraneoplastic antibodies, anti-GAD65), a substantial proportion develop AEAE despite adequate immunotherapy. Reference Smith, Britton and Thakolwiboon4,Reference Malter, Frisch and Zeitler5 While evidence for best ASM selection in such patients is limited, emerging data in antibody-specific cohorts (e.g. for use of cenobamate and clobazam combination in patients with anti-GAD65-associated temporal lobe epilepsy) give hope for a more personalised approach in the future. Reference Serrano-Castro, Rodríguez-Uranga and Cabezudo-García6

We share Dr Burneo’s view that, following reasonable exclusion of treatable neuroinflammation that could be contributing to seizure burden, patients with medically refractory AEAE may be considered for epilepsy surgery evaluation. It should be acknowledged, however, that evidence for efficacy of epilepsy surgery in patients with AEAE is limited. Furthermore, there is some data to suggest that, particularly for those with anti-GAD65-associated temporal lobe epilepsy, outcomes may be worse than expected when compared to other aetiologies. Reference Malter, Frisch and Zeitler5,Reference Mäkelä, Hietaharju, Brander and Peltola7,Reference Carreño, Bien and Asadi-Pooya8 Counselling on the uncertainty surrounding sustained benefit, as well as setting of realistic expectations, are thus essential to shared decision-making when contemplating epilepsy surgery in a patient with medically refractory AEAE.

Acknowledgements

None.

Author contributions

CH, AB and JM co-wrote the manuscript.

Funding statement

None.

Competing interests

AB reports that he holds the London Health Sciences Centre and London Health Sciences Foundation Chair in Neural Antibody Testing for Neuro-Inflammatory Diseases, and receives support from the Opportunities Fund of the Academic Health Sciences Centre Alternative Funding Plan of the Academic Medical Organization of Southwestern Ontario.

CH reports grant funding from the Alberta Neurosciences, Rehabilitation and Vision Strategic Clinical Network as well as honoraria from Alnylam, Akcea and Pfizer.

JM reports grant funding from the University of Alberta Department of Medicine, consulting fees from Novartis, educational honoraria from the American Academy of Neurology and participation in an advisory board for Horizon.

References

Hahn, C, Budhram, A, Alikhani, K, et al. Canadian consensus guidelines for the diagnosis and treatment of autoimmune encephalitis in adults. Can J Neurol Sci. 2024:121.Google ScholarPubMed
de Bruijn, MAAM, van Sonderen, A, van Coevorden-Hameete, MH, et al. Evaluation of seizure treatment in anti-LGI1, anti-NMDAR, and anti-GABA. Neurology. 2019;92:e2185e96.CrossRefGoogle ScholarPubMed
Liu, X, Guo, K, Lin, J, et al. Long-term seizure outcomes in patients with autoimmune encephalitis: a prospective observational registry study update. Epilepsia. 2022;63:1812–21.CrossRefGoogle ScholarPubMed
Smith, KM, Britton, JW, Thakolwiboon, S, et al. Seizure characteristics and outcomes in patients with neurological conditions related to high-risk paraneoplastic antibodies. Epilepsia. 2023;64:2385–98.CrossRefGoogle ScholarPubMed
Malter, MP, Frisch, C, Zeitler, H, et al. Treatment of immune-mediated temporal lobe epilepsy with GAD antibodies. Seizure. 2015;30:5763.CrossRefGoogle ScholarPubMed
Serrano-Castro, PJ, Rodríguez-Uranga, JJ, Cabezudo-García, P, et al. Cenobamate and clobazam combination as personalized medicine in autoimmune-associated epilepsy with Anti-Gad65 antibodies. Neurol Neuroimmunol Neuroinflamm. 2023;10:e200151.CrossRefGoogle ScholarPubMed
Mäkelä, KM, Hietaharju, A, Brander, A, Peltola, J. Clinical management of epilepsy with glutamic acid decarboxylase antibody positivity: the interplay between immunotherapy and anti-epileptic drugs. Front Neurol. 2018;9:579.CrossRefGoogle ScholarPubMed
Carreño, M, Bien, CG, Asadi-Pooya, AA, et al. Epilepsy surgery in drug resistant temporal lobe epilepsy associated with neuronal antibodies. Epilepsy Res. 2017;129:101–5.CrossRefGoogle ScholarPubMed