Mesial temporal lobe epilepsy (MTLE) is the most common form of focal intractable epilepsy in adults, associated with spontaneous recurrent seizures, hippocampal sclerosis, and long-term memory deficits. Approximately one-third of epilepsy patients do not respond to antiseizure medications, making invasive treatments such as resective surgery, ablative procedures, or neurostimulation important treatment options.
Although surgical treatment is the only curative option for medication-resistant epilepsy patients, it is not feasible when the seizure onset zone is not clearly identifiable or lies in certain brain regions. Neurostimulation via implanted devices offers an alternative for patients ineligible or reluctant to undergo surgery. A new approach called low-frequency stimulation (LFS) has shown promising seizure reduction in animal studies and small clinical cohorts, but how it works and the long-term effects remain unknown.
In a recent study, researchers aimed to identify the antiepileptic and cognitive outcomes and potential underlying biological mechanisms of long-term hippocampal LFS in chronically epileptic mice. During the chronic phase of epilepsy in the mice, researchers applied LFS and examined its effects on epileptiform activity, spatial memory, and pathological synaptic features in the brain. Long-term hippocampal LFS consistently diminished focal seizures in epileptic mice, with seizure reduction extending beyond the stimulation period. Additionally, long-term LFS reduced spatial memory deficits and reversed pathological changes in the brain shortly after stimulation. LFS had no significant effect on secondarily generalized seizures, anxiety-like behavior, neurogenesis, hippocampal sclerosis, or presynaptic vesicles in certain neural pathways.
These findings provide clinically relevant insights into the seizure type-specific effects of hippocampal LFS, and support the idea that it could contribute to enhanced seizure control and quality of life in MTLE patients.
