Epileptic Prodromal Alzheimer’s Disease Treated with Antiseizure Medications: Medium-Term Outcome of Seizures and Cognition

Article type: Research Article

Authors: Hautecloque-Raysz, Geoffroy^{a; b} | Sellal, François^{a; b; c} | Bousiges, Olivier^{d; g} | Phillipi, Nathalie^{a; e; f; g} | Blanc, Frédéric^{a; e; f; g} | Cretin, Benjamin^{a; e; f; g; *}

Affiliations: [a] Centre Mémoire, de Ressources et de Recherche d’Alsace (Strasbourg-Colmar), Strasbourg, France | [b] Service de Neurologie, Hospices Civils de Colmar, Colmar, France | [c] Unité INSERM U-1118, Faculté de Médecine de Strasbourg, Strasbourg, France | [d] University Hospital of Strasbourg, Laboratory of Biochemistry and Molecular Biology, and CNRS, Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR7364, Strasbourg, France | [e] Unité de Neuropsychologie, Service de Neurologie des Hôpitaux Universitaires de Strasbourg, Strasbourg, France | [f] University of Strasbourg and CNRS, ICube laboratory UMR 7357 and FMTS (Fédération de Médecine Translationnelle de Strasbourg), team IMIS/Neurocrypto Strasbourg, Strasbourg, France | [g] Centre de Compétences des démences rares des Hôpitaux Universitaires de Strasbourg, Strasbourg, France

Correspondence: [*] Correspondence to: Benjamin Cretin, MD-Msc, CMRR d’Alsace, Service de Neurologie des Hôpitaux Universitaires de Strasbourg, Pôle Tête et Cou, 1 Avenue Molière 67200 Strasbourg, France. Tel.: +33 3 88 12 86 32; Fax: +33 3 88 12 86 36; E-mail: [email protected].

Abstract: Background:The medium term outcome (over more than one year) of epileptic prodromal AD (epAD) patients treated with antiseizure medications (ASMs) is unknown in terms of seizure response, treatment tolerability, and cognitive and functional progression. Objective:To describe such medium term outcome over a mean of 5.1±2.1 years. Methods:We retrospectively compared 19 epAD patients with 16 non-epileptic prodromal AD (nepAD) patients: 1) at baseline for demographics, medical history, cognitive fluctuations (CFs), psychotropic medications, MMSE scores, visually rated hippocampal atrophy, CSF neurodegenerative biomarkers, and standard EEG recordings; 2) during follow-up (FU) for psychotropic medications, MMSE progression, and conversion to dementia. In the epAD group, we analyzed baseline and FU types of seizures as well as each line of ASM with the corresponding efficacy and tolerability. Results:At baseline, the epAD group had more CFs than the nepAD group (58% versus 20%, p = 0.03); focal impaired awareness seizures were the most common type (n = 12, 63.1%), occurring at a monthly to quarterly frequency (89.5%), and were well controlled with monotherapy in 89.5% of cases (including 63.1% seizure-free individuals). During FU, treated epAD patients did not differ significantly from nepAD patients in MMSE progression or in conversion to dementia. Conclusion:Epilepsy is commonly controlled with ASMs over the medium term in epAD patients, with similar functional and cognitive outcomes to nepAD patients. Pathophysiologically, epilepsy is likely to be an ASM-modifiable cognitive aggravating factor at this stage of AD.

Keywords: Alzheimer’s disease, antiseizure medications, cerebrospinal fluid, late-onset epilepsy, mild cognitive impairment

DOI: 10.3233/JAD-221197

Journal: Journal of Alzheimer's Disease, vol. 94, no. 3, pp. 1057-1074, 2023