Definition and diagnostic criteria of sleep-related hypermotor epilepsy

Abstract

The syndrome known as nocturnal frontal lobe epilepsy is recognized worldwide and has been studied in a wide range of clinical and scientific settings (epilepsy, sleep medicine, neurosurgery, pediatric neurology, epidemiology, genetics). Though uncommon, it is of considerable interest to practicing neurologists because of complexity in differential diagnosis from more common, benign sleep disorders such as parasomnias, or other disorders like psychogenic nonepileptic seizures. Moreover, misdiagnosis can have substantial adverse consequences on patients' lives. At present, there is no consensus definition of this disorder and disagreement persists about its core electroclinical features and the spectrum of etiologies involved. To improve the definition of the disorder and establish diagnostic criteria with levels of certainty, a consensus conference using formal recommended methodology was held in Bologna in September 2014. It was recommended that the name be changed to sleep-related hypermotor epilepsy (SHE), reflecting evidence that the attacks are associated with sleep rather than time of day, the seizures may arise from extrafrontal sites, and the motor aspects of the seizures are characteristic. The etiology may be genetic or due to structural pathology, but in most cases remains unknown. Diagnostic criteria were developed with 3 levels of certainty: witnessed (possible) SHE, video-documented (clinical) SHE, and video-EEG-documented (confirmed) SHE. The main research gaps involve epidemiology, pathophysiology, treatment, and prognosis.

Sleep-related hypermotor epilepsy

“…Familial cases represent ≈14% of our cohort, confirming that inherited genetic SHE represents a restricted condition in the broad etiologic spectrum of this syndrome. 1,15 …”

“…Diagnosis of SHE was based on level of certainty according to the new diagnostic criteria (figure e-1). 1 …”

“…Because current diagnostic criteria do not specify the all-life proportion of seizures arising from sleep with respect to wakefulness, 1 we labeled the frequency of sleep-related seizure according to the following categories: (1) 100% sleep-related seizures, i.e., no seizures during wakefulness lifetime (these patients were labeled as having a typical SHE pattern); (2) sleep-related seizures >75%, i.e., the frequency of seizures during sleep largely predominated seizures in wakefulness lifetime; and (3) sleep-related seizures <75%, i.e., the proportion of seizures from sleep slightly exceeded seizures during wakefulness; these patients were excluded from the study.…”

“…The clinical features and diagnostic criteria of SHE were recently revised during an international consensus conference (figure e-1 at Neurology.org). 1 …”

GATOR1 complex: the common genetic actor in focal epilepsies

“…The role of each protein in these complexes has still to be fully clarified, but the conservation of the mTOR pathway architecture across different species suggests that each partner of the complex carries out fundamental functions 14. Recently, mutations in the genes encoding the components of the GATOR1 subcomplex have been associated with several genetic focal epilepsy (FE) syndromes, including autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE, MIM 600513), recently renamed as autosomal-dominant sleep-related hypermotor epilepsy;15 epilepsy with auditory features (EAF, also known as lateral temporal lobe epilepsy, TLE, MIM 600512); familial FE with variable foci (FFEVF, MIM 604364) 16–20 . DEPDC5 mutations have also been recently described in patients manifesting rolandic epilepsy or epileptic spasms 21 22…”