Lack of heart rate variability during sleep-related apnea in patients with temporal lobe epilepsy (TLE)-an indirect marker of SUDEP?

Abstract

Apneas occurring during sleep may precipitate autonomic instability in epilepsy patients making them susceptible to sudden death (SUDEP). Literature on heart rate variability (HRV) during apnea among patients with temporal lobe epilepsy (TLE) is sparse. The aim of this study was to characterize the HRV during the peri-apneic period in patients with TLE and compare with HRV of matched healthy individuals during the overnight polysomnographic (PSG) recording. Further, the role of carbamazepine (CBZ) in modulating peri-apneic HRV in the above cohort was also assessed. Twenty patients diagnosed to have TLE (drug naive (n=10) or on CBZ monotherapy (n=10)) were compared with ten healthy controls. In both patients and controls, the time domain, frequency domain, and non-linear HRV indices were analyzed for 2min before and after apnea/hypopnea termination and compared using paired t test (p≤0.05). Additionally, the changes in HRV parameters in the peri-apnea/hypopnea period were compared between the three groups using one-way ANOVA followed by post hoc comparison (p≤0.05). The three study groups were age (p=0.21) and gender (p=0.27) matched. In controls (M/F=5:5; mean age 24.3±5.0years), there were significant changes in standard deviation of RR interval (SDNN), low frequency (LF) component and long-term HRV (SD2) parameters in the peri-apnea/hypopneic period. Conversely, in drug-naive TLE (M/F=6:4; mean age: 22.8±4.1years), all the HRV parameters, including non-linear measures were comparable in the pre- and post-apneic period. On the other hand, patients on CBZ (M/F=6:4; mean age 20.5±4.8years) showed significant changes in low-frequency nu (LFnu) and high-frequency nu (HFnu) components in the peri-apnea/hypopneic period. Comparison of the changes in HRV parameters in the peri-apnea/hypopnea period in patients with TLE and controls showed significantly lower changes in drug-naive TLE patients in SDNN, LF, and SD2 as compared to controls. This study showed that there was a lack of apnea-mediated HRV changes in patients with drug-naive TLE. This might suggest a possible alteration in reflex baroreceptor activation in patients with TLE, predisposing them to SUDEP, and this may be worsened with CBZ.