EPILEPSY: Stimulating the cerebellum to fight absence seizures

The team led by Dr Jan Claudius Schwitalla and Professor Melanie Mark from the RUB Behavioral Neuroscience research group recalls that more than 1.5 million people worldwide suffer from absence seizures, whether these absence seizures or ” petit mal”, can recur daily up to a hundred times and can interfere with normal functioning. Patients fall into a kind of behavioral paralysis that lasts a few seconds. Finally, absence seizures particularly affect children aged 4 to 12 years.

A very largely and profoundly altered brain activity

The recordings show brain activity exhibiting “spike-and-wave discharges” (SWDs). While the deep nuclei of the cerebellum have a very extensive connectivity and across different regions of the brain, the researchers hypothesized that by stimulating them, it would then be possible to reduce absence seizures. Moreover, experiments in mice had already suggested that such stimulation can indeed stop absence seizures.

Cerebellar Stimulation vs Altered Brain Activity: the researchers observe:

  • a lack of calcium channel in the cerebellar nerve cells of mouse models of absence seizures;
  • the cells of the cerebellar nuclei activate abnormally;
  • the stimulation of these cells makes it possible to prevent spike-wave discharges;
  • stimulation of the cerebellar nuclei by administration of a pharmacological substance or by chemogenetic stimulation effectively prevents the appearance of other SWDs in mice;
  • finally, the use of optogenetic stimulation to briefly increase the activity of the cells of the cerebellar nuclei also makes it possible to stop the SWD in progress, following they have been triggered.

Thus, taken together, these results support targeted stimulation of the cerebellar nuclei as a promising therapeutic approach for absence seizures.

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