Apnoeic-tonic seizures are only one type of seizure presented by people with the Lennox-Gastaut syndrome. These are people with a variety of seizure types, including absences, tonic clonic, myoclonic seizures and drop attacks. Various of these seizure types are resistant to drug therapy. Patients are as a rule on various drugs in high doses.
Apnoeic-tonic seizures called my attention very early on. It was in the context of Lennox-Gastaut syndrome and it led to a publication that will soon be 40 years old:
Bittencourt PR, Richens A. Anticonvulsant-induced status epilepticus in Lennox-Gastaut syndrome. Epilepsia. 1981 Feb;22(1):129-34.
It was a case report of a 22-year-old woman who developed series of apnoeic-tonic seizures with concomitant bursts of repetitive spikes at 16-20/sec, after receiving therapeutic doses of chlormethiazole, clonazepam, and diazepam for the treatment of serial tonic-clonic generalized seizures. There was a direct relationship between dose of chlormethiazole and frequency of seizures. My conclusion at the time was that the seizures were being driven by the drugs.
Now investigators in Australia have used dynamic causal modelling analysis of scalp EEG and fMRI during apnoeic and tonic seizures . They established that the brain networks that generate interictal generalized paroxysmal fast activity involve frontal cortex, spreading to brainstem and then thalamus. The middle frontal gyrus in the pre-frontal cortex may be the primary generator. The extrapyramidal corticoreticular includes projections from the caudal middle frontal gyrus to the pontomedulary reticular formation, which connects to spinal motoneurons. The study involved 25 patients.
Csaba Juhász. Neurology 2019, 93:91-92 – editorial
Warren et al. Neurology 2019, 93:e215-e226 – original paper
But because the study was of interictal discharges they could not eliminate the possibility that the precuneus or angular gyrus could be generators, specially of tonic seizures.
The authors did not contemplate the possibility that the seizures were related with their drug therapy, in special benzodiazepine drugs frequently used in these patients.
Dr Paulo Bittencourt
