Electro-clinical features and management of the late stage of Lafora disease

Giuseppe d'Orsi; Maria Teresa Di Claudio; Orazio Palumbo; Massimo Carella

doi:10.3389/fneur.2022.969297

Electro-clinical features and management of the late stage of Lafora disease

Front Neurol. 2022 Oct 5:13:969297. doi: 10.3389/fneur.2022.969297. eCollection 2022.

Authors

Giuseppe d'Orsi^{1

2}, Maria Teresa Di Claudio^{1

2}, Orazio Palumbo³, Massimo Carella³

Affiliations

¹ Neurology Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
² Department of Neurological Sciences, Policlinico Riuniti, University Neurology Unit, Foggia, Italy.
³ Division of Medical Genetics, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.

Abstract

Purpose: The aim of this study was to elucidate the electro-clinical features and management of the late stage of Lafora disease (LD).

Methods: We investigated the electro-clinical data and medical complications of three LD patients with mutations in EPM2A and two in NHLRC1 genes during the LD late stage.

Results: The late stage emerged after a mean period of 7 ± 1.41 years from the onset of the disease. All patients developed gait ataxia becoming bedbound with severe dementia. Pluri-monthly and drug-resistant myoclonic seizures, and myoclonic absence and tonic-clonic seizures were associated with daily/pluri-daily myoclonus, while the EEG/polygraphic findings showed diffusely slow activity with epileptiform abnormalities, often correlated with myoclonic jerks. Seizure emergencies with motor cluster/status epilepticus and medical complications dominated the clinical picture. In particular, video-EEG/polygraphic recordings disclosed status epilepticus with prominent motor symptoms of different subtypes refractory to IV new anti-seizure medications and responsive in 75% of cases to IV phenytoin. The main complications were dysphagia, aspiration pneumonia, acute respiratory failure, sepsis, immobility, and spasticity with bedsores. A coordinated and multidisciplinary management of the three patients with EPM2A mutations has demonstrated a reduction in seizure emergencies, medical complications and days of hospitalization, and a prolongation of the years of disease compared to the two patients with NHLRC1 mutations.

Conclusion: Status epilepticus with prominent motor symptoms of different subtypes, often responsive to IV phenytoin, and multiple medical complications characterize the LD late stage. An effective management requires a multidisciplinary medical and nursing team, coordinated by an epileptologist with the aim of reducing seizure emergencies and medical complications.

Keywords: Lafora disease; electro-clinical features; late stage; management; medical complications; status epilepticus.