Description:
<jats:sec><jats:title>Purpose</jats:title><jats:p>To evaluate the electro-clinical features in association with laboratory and instrumental correlates of neurodegeneration to detect the progression of Lafora disease (LD).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We investigated the electro-clinical longitudinal data and CSF Aβ42, p-tau<jats:sub>181</jats:sub> and t-tauAg, amyloid, and <jats:sup>18</jats:sup>F-FDG PET of five unrelated LD families.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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<jats:sub>181</jats:sub> 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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>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.</jats:p></jats:sec>