Towards a non-invasive interictal application of hypothermia for treating seizures: a feasibility and pilot study

Abstract

Objectives: To evaluate the feasibility and safety of head-neck cooling in conscious normal volunteers (10) and patients with medically refractory epilepsy (5) without causing shivering.

Patients and methods: We used a non-invasive head-neck cooling system (CoolSystems Inc., Lincoln, CA, USA). The tympanic temperature (TT) and intestinal temperature (IT) were measured as two measurements of 'core temperature' (CT), and multi-site external temperatures, several physiologic variables and EEG were monitored. Seizure counts over 4-week precooling, treatment and follow-up phases were compared.

Results: All 15 participants completed all the cooling sessions without significant complaints. At the end of 60 min of cooling, scalp temperature fell on average by 12.2 degrees C (P < 0.001), TT by 1.67 degrees C (P < 0.001), and IT by 0.12 degrees C (P = NS). Average weekly seizure frequency decreased from 2.7 to 1.7 events per patient per week (MANOVA: P < 0.05).

Conclusions: Non-invasive head-neck cooling is safe and well-tolerated. Initial pilot data in patients suggest that additional therapeutic studies are warranted.

Figure 1

Temperature changes before, during and after 60-min cooling of healthy volunteers. Arrows indicate start and end of cooling.

Figure 2

Weekly group seizure frequency (thick line) with a linear trend (broken line) and overall average* [*weekly 4-week average seizure frequency = all seizures for the group over the respective 4 weeks/20 · (five patients × 4 weeks)] during 4-week of baseline phase immediately prior to cooling, 4-week cooling phase and 4-week follow-up phase. The decrease in a weekly group 4-week average seizure frequency was statistically significant at 5% threshold level using the MANOVA (F = 15.202, DF = 2, Significance < 0.05)].