The pathophysiology of Lennox-Gastaut syndrome – a review of clinico-electrophysiological studies

Summary Introduction Lennox-Gastaut syndrome (LGS) is a type of therapy-resistant epileptic syndrome. Since the establishment of our Epilepsy Center in 1975 we have performed many studies to assess the clinical symptoms, seizure manifestations, sleep and long-term follow-up of the clinical course and changes on electroencephalographs (EEGs) in patients with LGS. Aim To review the updated pathophysiology of LGS based on our own clinico-electrophysiological data referring to recent advances in brain research. Methods All of our previously published and unpublished data were reviewed in order to investigate the pathophysiology of LGS and using PubMed database for relevant literature. Results and Discussion While LGS usually occurs in infancy, it has become apparent that there is a form of late-onset LGS (L-LGS) that may occur at age eight or older. L-LGS often occurs when there is a history of encephalitis/encephalopathy or status epilepticus. The long-term progression of LGS includes mainly tonic seizures that persist and are the basis of LGS. In approximately 30% of cases, the basic symptoms of LGS remain 10 years or longer after long-term progression, while the rest lose their characteristics, although the condition is residual in 60% of cases and remission occurs in fewer than 10%. Among the characteristic seizures associated with LGS, atypical absence seizures occur in response to a diverse range of EEG features; wherein, while they are mostly short, they are accompanied by a state of enervation along with a tendency for it to be unclear when the seizure has ended. Drop attacks can in fact be categorized into those in which the subject falls over due to hypertonia in the muscles used to maintain body posture and those in which the subject falls over due to loss of tension in the posture-retaining muscles. Tonic seizures range from those manifesting in the form of extremely mild axial muscle tonicity, open eyes and respiratory changes, accompanied by high voltage, fast rhythm (averaging 14 ± 0.4 Hz), or tonicity from axorhyzomelic muscles to the peripheral muscles, accompanying global tonic seizures, and EEG features showing low voltage fast activity (averaging 22 ± 0.6 Hz) from desynchronization. A total of 1191 clinical seizures were recorded upon overnight polysomnography and videotape, and seizure symptoms and their ictal EEGs were analyzed. In LGS, seizure activity increases during slow wave sleep, inhibiting progression into the further sleep stages but falls significantly during rapid eye movement (REM) sleep. Conclusions From the research into seizure symptoms, clinical progression, sleep and seizures during sleep, it was believed that in LGS epileptic native lesions occur due to mesencephalic reticular formation, in the thalamic reticular system and, as a result of recent of brain physiology research, it is considered that LGS is an epileptic reticulo-thalamo-cortical system disorder. This has been supported by EEG-fMRI findings (Siniatchikin et al., 2011). Further research is therefore necessary to elucidate the role of the reticular formation in controlling the thalamo-cortical networks in humans.