Epilepsy related to focal neuronal lipofuscinosis: extra-frontal localization, EEG signatures and GABA involvement.
Dysmorphic appearing neurons
Focal cortical Dysplasia
Focal seizures
GABA
Lipofuscinosis
MEA
SEEG
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
Aug 2022
Aug 2022
Historique:
received:
11
10
2021
accepted:
11
02
2022
revised:
07
02
2022
pubmed:
8
3
2022
medline:
22
7
2022
entrez:
7
3
2022
Statut:
ppublish
Résumé
Focal neuronal lipofuscinosis (FNL) is an uncommon epileptic disorder related to an excess of lipofuscin accumulation within dysmorphic-appearing neurons (DANs), whose epileptogenic mechanisms are still poorly understood. It shares some clinical and neuroimaging similarities with focal cortical dysplasia of type IIb (FCDIIb), but it represents a different pathological entity. Here, we identified two patients with FNL among a 10-year cohort of 323 patients who underwent neurosurgery for a focal pharmacoresistant epilepsy. We describe the electroclinical, metabolic and neuropathological features of both patients with FNL who benefited from a comprehensive presurgical investigation. While the previous reports showed frontal lobe localization of the lesion, FNL was identified in the temporal lobe, in one of our patients. EEG investigations in both patients showed striking focal and rich interictal activity resembling that described in FCDIIb. Besides focal intraneuronal lipofuscin accumulation, the neuropathological analysis demonstrated that somata of DANs were surrounded by a large amount of GABAergic presynaptic buttons, suggesting the involvement of interneurons in the epileptogenicity of FNL. To further explore the role of GABAergic transmission in the generation of epileptiform activity in FNL, we performed in vitro multi-electrode array recordings on the post-surgery tissue from one patient. Spontaneous interictal-like discharges (IILDs) were identified only in the restricted area displaying the highest density of lipofuscin-containing DANs, suggesting a close correlation between the density of lipofuscin-containing neurons and epileptogenicity. Moreover, IILDs were blocked by the GABAA receptor antagonist gabazine. All together, these findings showed how GABA signaling may contribute to the generation of interictal-like activity in FNL tissue.
Identifiants
pubmed: 35254479
doi: 10.1007/s00415-022-11024-y
pii: 10.1007/s00415-022-11024-y
doi:
Substances chimiques
Lipofuscin
0
gamma-Aminobutyric Acid
56-12-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4102-4109Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.
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