A unifying hypothesis for the pathogenesis of absence seizures, involving the thalamocortical circuitry, is proposed in a neurological progress report from the University of Southern California School of Medicine, Childrens Hospital Los Angeles. Abnormal oscillatory rhythms generated in the circuit involve g-aminobutyric acid (GABA)B-mediated inhibition alternating with glutamate-mediated excitation which triggers a low-threshold calcium current in neurons of the nucleus reticularis thalami. The process is modulated by pathways utilizing various neurotransmitters and projected onto the thalamus and cortex, generating bilaterally synchronous spike wave discharges and absence seizures. Ethosuximide and trimethadione block absence seizures by reducing the low-threshold calcium current via a direct action at the T-type calcium channel. Other anti-absence seizure medications have indirect effects on this calcium current within the thalamus. [1]

COMMENT. A knowledge of the mechanisms of absence seizures should facilitate the development of more specific antiepileptic medications and the avoidance of drugs (eg. phenytoin and carbamazepine) that exacerbate absence attacks. For an excellent review of mechanisms of antiepileptic drug action see Talwar D, 1990, and commentary, Progress in Pediatric Neurology I, 1991, pp94-5.