Application of Focal Cerebral Cooling for the Treatment of Intractable Epilepsy

Abstract

Epilepsy is usually treated with medication, but adequate seizure control is still not achieved in over 30% of epilepsy patients, even with the best available agents. Surgical treatment is also performed for such patients, but is not always successful. Focal cooling of the brain using a thermoelectric device has recently been evaluated as an alternative to epilepsy surgery. Brain cooling was first proposed approximately 50 years ago as an effective method for suppressing epileptic discharges (EDs). Recent studies indicate that focal cooling of the brain to a cortical surface temperature of 209 C to 259 C terminates EDs without inducing irreversible neurophysiological dysfunctions or neuronal damage in the brain tissue. Several mechanisms have been proposed for the antiepileptic effects of focal cooling, including reduction in neurotransmitter release, alternation of activation-inactivation kinetics in voltage-gated ion channels, and the slowing of catabolic processes. Developments in the implantable cooling device with closed-loop cooling systems for seizure detection and focal cooling have been promoted in the field of neuromodulation, but several aspects remain uncharacterized concerning the hardware. Recent advances in precision devices have enabled the optimization of the implantable local cooling system, which may become clinically applicable in the near future.

Seizure onset predicts its type

“…It could also interact directly with the patient via a personalized electronic device, and might protect and relief anxiety, especially in the 10%-65% of the pharmacoresistant population that does not experience an epileptic aura. [29][30][31][32] Our proposed seizure type prediction algorithm, albeit being dependent on the performance of the detection algorithm, could serve to stage the degree of warning and intervention [33][34][35] depending on the risk of ictal discharges becoming symptomatic and evolving to a bilateral tonic-clonic clinical manifestation. Stepwise therapeutic increments adapted to seizures' biorhythms and acute drug administration are logical and much desired approaches in the field.…”

“…28 Seizure prediction algorithms offer an alternative, in theory, but so far systematic reviews have demonstrated limited performance and replicability. [29][30][31][32] Our proposed seizure type prediction algorithm, albeit being dependent on the performance of the detection algorithm, could serve to stage the degree of warning and intervention [33][34][35] depending on the risk of ictal discharges becoming symptomatic and evolving to a bilateral tonic-clonic clinical manifestation.…”

Mapping and mining interictal pathological gamma (30–100Hz) oscillations with clinical intracranial EEG in patients with epilepsy

“…The ability to define and characterize a network of brain-tissue that is involved in seizure generation or is required to modulate the process of seizure-generation is of increasing interest to clinicians, researchers, and the medical device industry. The presented methods may help guide the surgical implantation of electrodes for electrical pacemakers (Fisher et al, 2010; Fountas et al, 2005) or thermoelectric probes for focal cooling (Fujii et al, 2010). …”

Improving early seizure detection

“…The potential for using similar devices for delivery of other types of therapy (e.g. drugs, focal cooling) also exists [37–39]. …”