AUTHOR=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 

TITLE=Association of CSF and PET markers of neurodegeneration with electroclinical progression in Lafora disease

JOURNAL=Frontiers in Neurology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1202971

DOI=10.3389/fneur.2023.1202971

ISSN=1664-2295

ABSTRACT=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 A42, p-tau181 and t-tauAg, amyloid and 18F-FDG PET of 5 unrelated LD families.
Results: Three progressive electro-clinical stages were identified. The early phase was characterized by rare generalised tonic-clonic and focal visual seizures, followed by the occurrence of myoclonus after a period ranging from a 2 to 12 months. The intermediate stage, usually occurring after two years from the onset of epilepsy, was characterized by a worsening of epilepsy and myoclonus associated with a 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 and clusters of seizures or status epilepticus and medical complications. . Amyloid (CSF A42, amyloid PET) and neurodegenerative (CSF p-tau181 and t-tauAg, FDG-PET) biomarkers suggest a pattern of cognitive impairment of non-Alzheimer disease type. Eighty per cent of the LD patients showed a more severe hypometabolism in the second FDG-PET compared to the first scan performed in a lower phase; lateral temporal lobe and thalamus hypometabolism were associated with the presence of phase intermediate or late.
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 CSF traditional biomarkers improves the diagnostic accuracy of cognitive decline in LD patients, suggesting a cognitive impairment of non-Alzheimer disease type.