Carbamazepine affects autonomic cardiac control in patients with newly diagnosed epilepsy
Introduction
Epileptic seizures are frequently associated with changes in cardiac function (Buren, 1958, Buren and Ajmone-Marsan, 1960) including tacky- as well as brady-arrhythmia (Blumhardt et al., 1986, Keilson et al., 1989, Smith et al., 1989). The proposed mechanism for these changes is the spread of seizure discharges to autonomic centres in the cortical, limbic and hypothalamic structures (Wannamaker, 1985). Animal models of epilepsy suggests that even interictal epileptogenic activity may induce changes in the autonomic nervous system, which could result in cardiac arrhythmia (Lathers and Schraeder, 1982, Lathers et al., 1987). Clinical studies indicate that also patients with epilepsy may have impaired autonomic cardiovascular regulation in the interictal state, although it is unclear whether the observed reduction in cardiovascular responses is due to the epilepsy and the interictal discharges, or the treatment with antiepileptic drugs (AEDs) (Frysinger et al., 1993, Massetani et al., 1997, Isojarvi et al., 1998, Tomson et al., 1998, Ansakorpi et al., 2000, Ansakorpi et al., 2002). These observations are of particular interest considering the increased risk of sudden unexpected death among people with epilepsy (SUDEP) (Ficker et al., 1998) and the potential role for autonomic dysfunction in this context.
A recent study of heart rate variability demonstrated increased sympathetic activity in sleep after abrupt reduction of carbamazepine (CBZ) (Hennessy et al., 2001). Although these results suggest important effects of abrupt withdrawal of CBZ on autonomic cardiac control in patients with refractory epilepsy, the results cannot immediately be extrapolated to the general epilepsy population.The present study was therefore designed to assess directly the effect of CBZ on autonomic cardiac control by application of spectral analysis of heart rate variability to patients with newly diagnosed epilepsy before and after initiation of treatment with CBZ.
Section snippets
Patients
Adult patients with newly diagnosed epilepsy attending the Department of Neurology at the Karolinska Hospital in Stockholm, Sweden, were eligible for inclusion in the study. Only patients planned for CBZ treatment but without other AEDs were included. Patients with a history of heart failure, coronary heart disease, diabetes, uraemia or any other known disease that might affect the autonomic nervous system were excluded, as were patients with brain tumours and those for which immediate
Results
All patients had been seizure free at least 24 h before the EKG-recordings and none reported any seizures during the recordings. When analysing the full 24 h recording, patients had significantly lower standard deviation of RR-intervals, TP, VLF, LF and HF during treatment with CBZ than before, but there was no significant change in the LF/HF ratio (Table 2). The results were very similar when daytime (Table 3) and night time (Table 4) recordings were analysed separately.
Discussion
We used spectral analysis of heart rate variability to assess autonomic cardiac control in the present study. With this method, it is possible to partly separate the sympathetic components from the vagal components of the power spectrum (van Ravenswaaij-Arts et al., 1993). HF reflects respiratory sinus arrhythmia and is mainly related to parasympathetic activity (Katona and Jih, 1975, Akselrod et al., 1981, Pomeranz et al., 1985). LF oscillations are associated with baroreflexor control of
Acknowledgements
This study was supported by grants from the Karolinska Institute and by the Follin Foundation.
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2021, Epilepsy and BehaviorCitation Excerpt :Beat-to-beat BP and HR were recorded at 0, 1, 2, 3, and 5 min. The sample size was estimated using Open Epi software version 3.01 as 46 in each group and was calculated using the previous information that CBZ reduces the SDRR interval by 10–25% [11] to achieve 80% power and 95% CI assuming that the cases will have a mean reduction in SD of RR interval of 13 ms compared to controls (63 ms vs 50 ms) and the ratio of cases to controls being one. The normality of the data was assessed using Kolmogorov–Smirnov (KS) test.