Absences (generalised seizures)
This type of generalised seizure is localized in the central region of the brain in the thalamus and spreads over both hemispheres. The most probable mechanism of an absence (also called petit mal) is abnormal synchronization of thalamocortical and cortical cells. The absence is characterized by activation of T-type calcium channels on the thalamic relay neurons. The pathophysiological process begins with a certain signal from the cortex towards the thalamic area. This can include increased cellular potassium, increased GABAergic input or decreased excitatory input.
This stimulus evokes hyperpolarisation of the thalamic area (1). Following the hyperpolarisation, the T-type calcium channels are activated (2). The burst activity of the T-type calcium channels results in a synchronous depolarisation of excitatory neurons projecting to the cortical regions (3). The calcium influx provokes release of synaptic vesicles containing the excitatory glutamate. This can be seen on an EEG as a typical 3/sec spike and wave discharge. The excitatory input from the cortex activates the reticular thalamic neurons (4). The activated GABA-neurons in the thalamic area hyperpolarize the thalamic relay neurons again and so start a new loop.
A 9-year-old girl is diagnosed with absences. Which of the following drugs is NOT an appropriate choice to treat the patient?
Extra info: Ethosuximide is the drug of choice, valproic acid secondary, and phenobarbital with refractory cases. There is clinical evidence that carbamazepine may increase the incidence of absences.