Status epilepticus in POLG disease: a large multinational study

Abstract

We aimed to provide a detailed phenotypic description of status epilepticus (SE) in a large cohort of patients with POLG disease and identify prognostic biomarkers to improve the management of this life-threatening condition. In a multinational, retrospective study with data on patients with POLG disease from seven European countries, we identified those who had SE. The age of SE onset, accompanying clinical, laboratory, imaging and genetic findings were analysed. One hundred and ninety-five patients with genetically confirmed POLG disease were recruited, of whom 67% (130/194) had epilepsy. SE was identified in 77% (97/126), with a median age of SE onset of 7 years. SE was the presenting symptom of the disease in 43% (40/93) of those with SE, while 57% (53/93) developed SE during the disease course. Convulsive SE was reported in 97% (91/94) followed by epilepsia partialis continua in 67% (56/84). Liver impairment 78% (74/95), ataxia 69% (60/87), stroke-like episodes 57% (50/88), were the major comorbidities. In the majority (66%; 57/86) with SE this became refractory or super-refractory. The presence of seizures was associated with significantly higher mortality compared to those without (P ≤ 0.001). The median time from SE debut to death was 5 months. SE is a major clinical feature of POLG disease in early and juvenile to adult-onset disease and can be the presenting feature or arise as part of a multisystem disease. It is associated with high morbidity and mortality, with the majority of patients with SE going on to develop refractory or super-refractory SE.

Keywords: POLG; Epilepsy; Mitochondrial disease; Refractory status epilepticus.

Fig. 1

Age of disease onset and onset of status epilepticus for the whole study cohort of patients with POLG disease and also according to the gender. A Age of disease onset for the whole study cohort. B Age of onset of status epilepticus (SE). C Age of onset of SE in males. D: Age of onset of SE in Females

Fig. 2

Summary of 195 patients with POLG disease stratified according to presence or absence of seizures, status epilepticus and age of onset of disease, seizures, and status epilepticus. Epilepsy developed in 67%. The majority of those with epilepsy were in the early (61%) and juvenile to adult-onset (38%) disease groups. Of those with epilepsy, 77% developed status epilepticus (SE) with a median age of SE onset of 7 years. SE is mainly manifested in early (56%) and juvenile to adult (37%) onset disease groups