Clinical subtypes and sleep-wake evolution pattern in epilepsy manifesting as sleep-related seizures.

Cluster-based classification of epilepsy manifesting as sleep-related seizures, defined by at least 80% of seizures occurring during sleep, and description of its sleep-wake evolution.

This cross-sectional study included 550 patients with epilepsy manifesting as sleep-related seizures, defined by at least 80% of seizures occurring during sleep, classified as current or previous depending on whether that threshold was met over the past year. A two-step cluster analysis split the current cohort (n = 447) into two subtypes: a sleep tonic-clonic seizure subtype (n = 218) with later onset (18.0 years), infrequent seizures (fewer than one per month in 73.9%), unknown aetiology in 78.0% and favourable drug response (2.8% drug-resistant epilepsy); and a sleep non-tonic-clonic subtype (n = 229) with earlier onset (11.0 years), frequent focal seizures (at least one per month in 52.0%), malformations of cortical development in 27.9% and drug resistance in 62.9%. In the previous-EpSRS cohort (n = 103), an evolution was observed from the sleep tonic-clonic subtype towards an awake focal seizure pattern, with 52.5% diagnosed as temporal lobe epilepsy and drug resistance rising from 5.2% to 39.0%. This phenotypic evolution was predicted by later age at epilepsy onset, female sex and a history of febrile seizures.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The value here is aetiological before it is prognostic: early onset with frequent, drug-resistant nocturnal focal seizures points first to a malformation of cortical development, hence to imaging and possibly to a somatic brain mosaicism hypothesis, whereas the later-onset tonic-clonic subtype of unknown aetiology is the profile where germline genomic testing has most to prove. The design sets the limits: the subtypes come from a statistical partition of a single cross-sectional cohort and need independent replication, and the described trajectory rests on comparing two distinct groups rather than following the same patients over time. The shift towards an awake seizure pattern, with drug resistance rising from 5.2% to 39.0%, is nonetheless worth presenting as a warning signal to monitor rather than as an individual quantified risk.

Analysis by Dr Thibaut Benquey