Frontiers in Neurology (Jun 2023)

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

  • Giuseppe d'Orsi,
  • Andrea Farolfi,
  • Lorenzo Muccioli,
  • Orazio Palumbo,
  • Pietro Palumbo,
  • Sergio Modoni,
  • Vincenzo Allegri,
  • Valentina Garibotto,
  • Maria Teresa Di Claudio,
  • Ester Di Muro,
  • Mario Benvenuto,
  • Francesca Bisulli,
  • Francesca Bisulli,
  • Massimo Carella

DOI
https://doi.org/10.3389/fneur.2023.1202971
Journal volume & issue
Vol. 14

Abstract

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PurposeTo evaluate the electro-clinical features in association with laboratory and instrumental correlates of neurodegeneration to detect the progression of Lafora disease (LD).MethodsWe investigated the electro-clinical longitudinal data and CSF Aβ42, p-tau181 and t-tauAg, amyloid, and 18F-FDG PET of five unrelated LD families.ResultsThree 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-tau181 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.ConclusionsThree 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.

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