Time course and mapping of cerebral perfusion during amygdala secondarily generalized seizures

Measurement of local cerebral blood flow (LCBF) is routinely used to locate the areas involved in generation and spread of seizures in epilepsy patients. Because the spatial distribution and extent of ictal CBF depends on the epileptogenic network, but also on the timing of injection of tracer, we used a rat model of amygdala-kindled seizures to follow the time-dependent changes in the distribution of LCBF changes.

Rats were implanted in the left amygdala and were fully kindled. LCBF was measured by the quantitative [(14)C]iodoantipyrine autoradiographic technique bilaterally in 35 regions. The tracer was injected at 30 s before seizure induction (early ictal), simultaneous with the application of stimulation (ictal), at 60 s after stimulation (late ictal), at the end of the electrical afterdischarge (early postictal), and at 6 min after the stimulation (late postictal).

Rates of LCBF increased over control levels during the early ictal phase ipsilaterally in medial amygdala, frontal cortex, and ventromedian thalamus and bilaterally in the whole hippocampus, thalamic nuclei, and basal ganglia. During the ictal phase, all regions underwent hyperperfusion (81-416% increases). By 60 s after stimulation, rates of LCBF returned to control levels in most brain areas, despite ongoing seizure activity. At later times, localized foci of hypoperfusion were observed in hippocampus bilaterally, with a slight predominance in CA1 on the side of origin of the seizures.

This study shows a rapid spread of activation from the stimulated amygdala bilaterally to numerous limbic, cortical, and subcortical structures. The largest hyperperfusion was recorded during the ictal period with tracer injections simultaneous with the stimulation. The unilateral site of origin of seizures led to minor asymmetrical and lateralized findings, merely at early ictal and late postictal times, whereas intermediate tracer injections induced bilateral changes. Only late postictal measurements allowed the identification of significant changes in focal structures: the hippocampus is known to play a critical role in the spread of limbic seizures.