| Title: |
Association of CSF and PET markers of neurodegeneration with electroclinical progression in Lafora disease |
| Authors: |
d'Orsi, Giuseppe; Farolfi, Andrea; Muccioli, Lorenzo; Palumbo, Orazio; Palumbo, Pietro; Modoni, Sergio; Allegri, Vincenzo; Garibotto, Valentina; Di Claudio, Maria Teresa; Di Muro, Ester; Benvenuto, Mario; Bisulli, Francesca; Carella, Massimo |
| Source: |
ISSN: 1664-2295 ; Frontiers in neurology, vol. 14 (2023) 1202971. |
| Publication Year: |
2023 |
| Collection: |
Université de Genève: Archive ouverte UNIGE |
| Subject Terms: |
info:eu-repo/classification/ddc/616.0757; 18F-FDG PET; Lafora disease; Amyloid biomarkers; Electro-clinical features; Follow-up; Neurodegenerative biomarkers; Progressive myoclonic epilepsy |
| Description: |
Purpose: To evaluate the electro-clinical features in association with laboratory and instrumental correlates of neurodegeneration to detect the progression of Lafora disease (LD). Methods: We investigated the electro-clinical longitudinal data and CSF Aβ42, p-tau 181 and t-tauAg, amyloid, and 18 F-FDG PET of five unrelated LD families. Results: Three progressive electro-clinical stages were identified. The early phase was characterized by rare, generalized tonic-clonic and focal visual seizures, followed by the occurrence of myoclonus after a period ranging from 2 to 12 months. The intermediate stage, usually occurring 2 years after the onset of epilepsy, is characterized by a worsening of epilepsy and myoclonus associated with progressive dementia and cerebellar signs. Finally, the late stage, evolving after a mean period of 7 ± 1.41 years from the onset of the disease, was characterized by gait ataxia resulting in bedriddenness, severe dementia, daily/pluri-daily myoclonus, drug-resistant epilepsy, clusters of seizures or status epilepticus, and medical complications. Amyloid (CSF Aβ42, amyloid PET) and neurodegenerative (CSF p-tau 181 and t-tauAg, FDG-PET) biomarkers indicate a pattern of cognitive impairment of the non-Alzheimer's disease type. A total of 80% of the LD patients showed more severe hypometabolism in the second FDG-PET scan compared to the first scan performed in a lower phase; the lateral temporal lobe and the thalamus hypometabolism were associated with the presence of intermediate or late phase. Conclusions: Three electroclinical and 18F-FDG PET evolutive stages are useful biomarkers for the progression of LD and could help to evaluate the efficacy of new disease-modifying treatments. The combination of traditional CSF biomarkers improves the diagnostic accuracy of cognitive decline in LD patients, indicating a cognitive impairment of the non-Alzheimer's disease type. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/37448753; unige:177254 |
| Availability: |
https://archive-ouverte.unige.ch/unige:177254 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.9C492502 |
| Database: |
BASE |