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

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.

Figure 1

Video-EEG/polygraphic features of interictal pattern in patient 2 during the late stage. Repetitive, multifocal, asymmetrical and asynchronous, rhythmic and arrhythmic, myoclonic jerks associated with diffuse, multifocal, and faster discharges of SW/PSW.

Figure 2

Video-EEG/polygraphic features of myoclonic–tonic SE in patient 1 during the late stage. From the EEG/EMG point of view (see on the left), corresponding to the diffuse and fast paroxysms, myoclonic jerks mainly involving arms, superimposed on a tonic muscular enhancement, appeared; loss of awareness persisted between myoclonic–tonic events. IV diazepam 10 mg, IV lacosamide 400 mg, and IV levetiracetam 3,000 mg were ineffective. Myoclonic–tonic SE resolved after IV phenytoin 1,000 mg in 30 min (see on the right). The asterisks indicate the gradual control of myoclonic–tonic episodes after IV phenytoin.

Figure 3

Video-EEG/polygraphic features of focal motor SE in patient 2 during the late stage, with continuous myoclonic jerks in the left arm.