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Corresponding author at: Clinical Epidemiology and Biostatistics Department, Pontificia Universidad Javeriana, Medical School Carrera 7 No. 40–62, Bogota, Colombia.
Non-pharmacological treatment of epilepsy can alter sleep parameters.
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The vagus nerve stimulator can increase the risk of sleep apneas.
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The effects of surgery on sleep quality depend on the success of the procedure.
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Sleep parameters should be assessed before and after invasive procedures.
Abstract
Purpose
Perform a systematic review of the literature on the effects of vagus nerve stimulation (VNS), deep brain stimulation (DBS) and epilepsy surgery in subjective and objective sleep parameters.
Methods
We performed a literature search in the main medical databases: Medline, Embase, Cochrane, DARE and LILACS, looking for studies that evaluated the effects of VNS, DBS or epilepsy surgery on sleep parameters. In all, 36 studies, coming from 11 countries, including reviews, cohort studies, case series and case reports were included.
Results
VNS induces sleep apnoea dependent of the stimulation variables. This condition can be reverted modifying these settings. Surgical procedures for epilepsy cause an improvement in objective and subjective sleep parameters that depend on the success of the procedure evaluated through ictal frequency control. There is evidence that non-pharmacologic treatment of epilepsy has different effects on sleep patterns.
Conclusion
It is advisable to include objective and subjective sleep parameters in the initial evaluation and follow-up of patients considered for invasive procedures for epilepsy control, especially with VNS due to the risk of sleep apnoea. More high quality studies are needed.
In patients with epilepsy, multiple factors such as ictal frequency, interictal activity and anticonvulsant therapy affect sleep architecture and quality [
]. An increase in obstructive sleep apnoea/hypopnea syndrome (OSAHS) has been documented in patients with refractory epilepsy, in whom, with an incidence as high as 33% [
The objective of this systematic review was to evaluate current evidence on the effects of non-pharmacological treatments, including vagal nerve stimulation (VNS), deep brain stimulation (DBS) or epilepsy surgery on both objective and subjective sleep parameters.
2. Methods
2.1 Search strategy
We performed a systematic review of Medline (Pubmed), Embase, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects – DARE and Latin American and Caribbean Literature in Health Sciences – LILACS. Terms used and adapted for each database were:
(epilepsy OR epilepsies OR epileptic OR seizures)
AND
(surgery OR surgical OR “deep brain stimulation” OR DBS OR callosotomy OR lobectomy OR vagus)
AND
(Sleep OR REM OR insomnia OR somnolence OR sleepiness OR polysomnography OR somnography OR hypersomnia OR parasomnia OR osa OR apnea OR dreams)
We limited the search to articles with abstract available and published from January 1, 2000 to the present (search date June 15, 2016). There was no language restriction. We included meta-analyses or systematic reviews, randomized clinical trials, cohort studies, case series or individual case reports, focusing on the effect of epilepsy surgery, VNS or DBS on objective or subjective sleep parameters.
Initial exclusion of irrelevant articles, based on title and abstract, was done by 2 independent members of the research group (ORO, SGT); full-text versions were obtained for data extraction. The list of references of each study was analysed manually. Subsequently, the articles were classified according to the type of procedure, and according to the American Academy of Neurology's classification of evidence [
Fig. 1 shows the selection process. The initial search retrieved 2717 references, of which finally 36 articles with a class of evidence III and IV were reviewed; 15 came from United States; five from Italy, four from France; three from Canada, two from Sweden, and one each from Australia, Austria, Brazil, Cyprus, Finland, Germany, and India; 27 articles referred to VNS, 8 to epilepsy surgery and 1 to DBS.
Of the 27 articles on VNS (Table 1), 11 were case reports, nine prospective descriptive studies and seven retrospective descriptive studies. These included a total of 209 patients between the ages of 3 and 58 years.
Table 1Studies of the effects of the vagus nerve stimulator on sleep.
] found that the score on the Epworth scale improved from 7.2 ± 4.4 to 5.6 ± 4.5, unrelated to a decrease in ictal frequency or changes in the sleep stages through polysomnographic evaluation. These findings contrast with the case report of St Louis et al. [
] in which a patient developed snoring and an increase in the score on the Epworth scale following implantation of the VNS, both of which improved after reducing its pacing times.
] reported the case of a patient with deep sleep status epilepticus in which there was an improvement in the perception of well-being, also finding an association between the decrease in the number of crises with improvement in cognition, language, school performance and decrease in irritability. In the study by Galli et al. [
]. In all cases, the occurrence of apnoea was correlated with the ON period of the stimulator, and turning it off, or adjusting the setting with decreased stimulation parameters achieved an adequate control of respiratory symptoms in most patients [
Two studies with polysomnographic evaluation described the presence of vocal cord adduction during the ON stimulation period, evidenced by indirect laryngoscopy, associated with the onset or worsening of respiratory sleep disorder [
], suggesting a possible explanation for the mechanism by which the stimulator induces sleep apnoea.
In children, disturbances in the cardiorespiratory regulation were described during stimulation activation, including an increase in frequency and a decrease in respiratory amplitude, with variable changes from patient to patient in heart rate, which results in poor optimization of tissue oxygenation [
Other reported polysomnographic findings associated with VNS are: higher intensity of the stimulator attenuates the REM sleep, whereas lower intensity improves the wakeful state [
]. Stimulator discharges are associated with a significant increase in respiratory rate and a decrease in the range of abdominal distension, inducing a decrease in oxygen saturation [
The objective evaluation by means of electroencephalographic parameters (EEG) found that VNS produced an increase of the spectral power in the delta and theta wave EEG in non-REM sleep, and alpha waves in REM sleep and wakefulness, without significant decrease in interictal activity during sleep [
]. A decrease in the number of interictal epileptiform discharges, especially during REM and delta sleep were also described,as well as other minor alterations in the EEG [
] (Table 2); two of these are case-control studies, two prospective case series, two retrospective, and two case reports, with a total of 207 patients aged between 3 and 62 years.
Table 2Studies of the effects of epilepsy surgery on sleep.
], 17 patients with refractory focal epilepsy, mostly of the mesial temporal type, followed by frontal and parietal, found a statistically significant reduction in ictal frequency (p = .01) with improvement in self-reported sleep parameters, such as the duration of night-time sleep (p = .01), total sleep duration (p = .03), and a reduction in Epworth score (p = .02) in patients with good postoperative outcome. In the polysomnographic study, a decrease in AHI was found in patients with good postoperative outcome with respect to the basal state and the poor outcome group.
Four studies evaluated the effects of temporal lobe surgery for hippocampal sclerosis on sleep parameters, and found that patients with refractory temporal lobe epilepsy have poor sleep quality, as measured by the Pittsburgh scale, which improved after the procedure [
]. The presence of interictal epileptiform discharges predicts the onset of aura or epileptic seizures in the postoperative period; EEG during sleep allows the identification of these patients, since half of interictal discharges occur during sleep [
]. The adequate postoperative outcome resulted in a reduction of epileptic seizures, a decrease of interictal discharges, and even cognitive improvement [
]. In addition to decreased ictal frequency and interictal epileptiform activity, there was an increase in total sleep time, and in the percentage of REM sleep, with a decrease in the number of awakenings and in sleep latency [
In patients with nocturnal sleep epileptic status treated with hemispherectomy or local resection, there is improvement in ictal frequency and resolution of epileptiform activity, associated with improvement in neuropsychological tests [
], patients with refractory generalized epilepsy treated with right hemispherectomy found lower sleep efficiency, with no difference in total sleep time, sleep stage time, or sleep latency. Foldvary-Schaefer et al. [
] presented a patient with refractory frontal lobe epilepsy, who achieved significant improvement in severe sleep apnoea following the surgical procedure, associated with an improvement in ictal frequency.
3.3 Deep brain stimulation
A single prospective observational study of 9 patients undergoing DBS performed by Voges et al. [
] in Germany, with anterior thalamus stimulation for the treatment of refractory epilepsy, showed that this procedure increased the number of awakenings in a voltage-dependent manner with a consecutive increase in neuropsychiatric symptoms, which improved decreasing the stimulation voltage during sleep.
4. Discussion
This review compiles the literature published in the last 15 years on the effect of invasive procedures for the treatment of epilepsy on objective and subjective sleep parameters. These sleep patterns have been studied in a variety of procedures, and in populations of different ages. Conclusions are limited due to the number of studies and to their observational nature (class III and IV),;furthermore, results are not always consistent from one study to another. The review, however, highlights the importance of studying sleep in patients with epilepsy, not only because of the potential risk of seizures with sleep deprivation, but also because of the possibility of comorbidities associated with sleep disorders, such as cardiovascular risk posed by OSAHS. The association of sleep apnoea with VNS seems well substantiated, both in children and in adults. This association is consistent with the evidence of vagal inhibition as a means to reduce AHI in patients with severe OSAHS, described by Garrigue et al. [
], meaning its modification can reverse the effects without the need for other interventions in most patients. Perhaps patient comorbidities and risk factors, like age, body mass index or craniofacial anomalies, which are rarely taken into consideration [
], might influence the appearance of apnoea. It is therefore advisable to perform a sleep study in candidates for VNS and to monitor them periodically, in order to prevent and treat changes that may occur as a result of the procedure. A single study of deep brain stimulation [
] also shows that the variables of stimulation (frequency and intensity) can be modified to change possible adverse effects; in this case, an increase in the number of awakenings.
Regarding epilepsy surgery, evidence is clearly insufficient to draw solid conclusions, but apparently the effect of the procedure on sleep depends on the success of the procedure, and is directly associated with good control of the ictal frequency and the absence of postoperative complications [
A special case is status epilepticus of deep sleep, which is characterized by continuous slow-wave epileptic discharges during non-REM sleep, which leads to a progressive deterioration of cognition. This was studied in two cases [
], in which the control of ictal and interictal activity with hemispherectomy or VNS led to an improvement in both objective and subjective sleep parameters and cognition.
5. Conclusion
Given the importance of sleep, and the detrimental effect of related disorders in quality of life, it is advisable to include objective and subjective sleep parameters as part of the initial evaluation and follow-up of patients who are candidates for procedures for the control of epilepsy, in view of a new possible point of intervention in the integral management of the epilepsy patient.
Conflict of interest
None of the authors has any conflict of interest to disclose.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Ethical statement
As a systematic review of the literature, this study did not involve interventions on patients nor following them in time. The work described adheres to the principles of the Committee on Publication Ethics and is consistent with the Journal guidelines for ethical publication. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
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