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How are epileptic events linked to obstructive sleep apneas in epilepsy?
Seizure 24 (2015) 121–123
Contents lists available at ScienceDirect
Seizure journal homepage: www.elsevier.com/locate/yseiz
Clinical letter
How are epileptic events linked to obstructive sleep apneas in epilepsy? Vi-Huong Nguyen-Michel, Olivier Pallanca, Vincent Navarro, Sophie Dupont, Michel Baulac, Claude Adam * Epileptology Unit, Department of Neurology and Clinical Neurophysiology, Assistance Publique-Hoˆpitaux de Paris, Groupe hospitalier Pitie´-Salpeˆtrie`re and UPMC University Paris 06, CRICM (CNRS UMR-7225), 47-83 Boulevard de L’Hoˆpital, 75651 Paris cedex, France
A R T I C L E I N F O
Article history: Received 24 June 2014 Received in revised form 4 September 2014 Accepted 6 September 2014
1. Introduction Obstructive sleep apnea (OSA) is common in patients with refractory epilepsy and may exacerbate seizures. In epileptic patients with OSA, seizures occur more frequently during sleep.1 Seizure frequency may be reduced by treating OSA2–4 and increase if the treatment is interrupted or neglected.2,3 It is not clear how OSA provokes seizures. Multiple seizureprovoking factors including cerebral hypoxemia, sleep deprivation and sleep fragmentation1 might be involved. The temporal link between OSA and seizures or interictal events might be better understood with careful analysis of video EEG (vEEG) records. Such data has never been precisely reported. We report here a direct relation between OSA and both ictal and interictal epileptic events during vEEG investigations in a patient with temporal lobe epilepsy.
2. Case presentation A 43-year-old woman was admitted to the Epileptology unit for diagnostic purposes. She suffered from refractory post-traumatic epilepsy and experienced daytime partial and nocturnal secondarily generalized seizures. Cerebral MRI revealed no specific signs. FDG-PET showed a left temporal hypometabolism. Additionally, she was obese (body mass index 44 kg/m2) and experienced daytime sleepiness (Epworth score 18).
* Corresponding author at: Unite´ d’Epileptologie, Service de Neurologie 1, Clinique P. Castaigne, Hoˆpital de La Pitie´-Salpeˆtrie`re, 47-83 Boulevard de L’Hoˆpital, 75651 Paris cedex 13, France. E-mail address: [email protected] (C. Adam).
Ventilatory polygraphy investigation revealed a severe OSA syndrome (apnea hypopnea index (AHI) of 75/h). The mean oxygen saturation was 95%, the nadir 72% and the mean decline during apnea was 7%. A seven day vEEG monitoring investigation showed: (i) Incessant OSA consisting of loud snoring during sleep, which was interrupted by a silence, accompanied by visible abdominal efforts and ending in a loud, harsh, stridulous gasp and awakening. (ii) Frequent left temporal lobe spikes (Fig. 1 in supplementary material). (iii) Twelve left temporal lobe seizures consisted in oro-bucal automatisms followed by right-sided motor symptoms and sometimes secondary generalization. Seizures often occurred during sleep (11/12, 92%). Seven of these eleven seizures were associated with OSA (63%): one occurred during OSA without K complex or arousal, six during an awakening EEG activity either immediately (n = 4) or at 12 s and 65 s after an OSA. The remaining four seizures were preceded neither by OSA nor by arousal. (iv) Six 1.5–2.5 Hz symmetrical generalized high-amplitude spikewave (S-W) discharges each occurred during an OSA. They were prominent over anterior regions and formed part of a stereotyped electro-clinical sequence. Breathing stopped leading to a micro-arousal of 6.8 0.7 s (mean standard deviation) comprising a K complex and succeeding alpha run. This was followed by a S-W discharge of duration 10 4 s and terminated by a loud stridulous gasp and awakening (Fig. 1). These S-W discharges began about 10 s after the onset of the OSA and terminated about 2.5 s before (n = 4), or at the end of the OSA (n = 2). Discharges were generalized throughout, with an initial spike occurring sometimes slightly in advance in the left temporal region (n = 3). Compared with 30 successive isolated and randomly-chosen OSA episodes without generalized epileptic discharges, those preceding EEG discharges were more often associated with a micro-arousal (p = 0.048) of longer duration (p = 0.004) (Fischer Exact and Mann–Whitney test) (Table 1). (v) Sleep was very fragmented without deep and rapid eye movements sleep. The patient was treated with continuous positive airway pressure (CPAP). The rate of AHI decreased to 5/h (indicated by
http://dx.doi.org/10.1016/j.seizure.2014.09.004 1059-1311/ß 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
V.-H. Nguyen-Michel et al. / Seizure 24 (2015) 121–123
122
Fig. 1. Electro-clinical sequence of obstructive sleep apnea inducing unexpected generalized spike-wave discharge.
the CPAP machine) and seizure frequency decreased by 60%. One year later, a vEEG performed under CPAP and oxymetry showed normal sleep structure and normal oxygen saturation. When the patient voluntarily interrupted CPAP, she immediately experienced again incessant OSA, one typical left temporal lobe seizure and one generalized S-W discharge which were both OSA-related and without oxygen desaturation (Figs. 2 and 3 in supplementary material). 3. Discussion A link between OSA and epilepsy has been previously suggested.1–4 In this patient we describe the precise temporal link between the OSA and the epileptic events. We found seizures are often preceded by an OSA, reduced under CPAP and re-emerge immediately when CPAP is withdrawn. We also found an unexpected interictal EEG pattern of rhythmic generalized S-W discharges strictly related to OSA, disappearing under CPAP, and re-emerging after CPAP arrest. This interictal pattern has not been previously published and is likely the result of a secondary bilateral synchrony (i.e. a bilateral synchronous discharge arising from a unilateral epileptic focus) and is not of a primary generalized origin (indeed there was no suggestive clinical history and no spontaneous generalized discharges during two prolonged monitorings). This also differs completely from electro-clinical consequences of severe hypoxic cerebral damage with continuous pseudo-periodic S-W on a degraded background activity. Multiple hypotheses including cerebral hypoxemia, sleep deprivation or fragmentation1 have been advanced to explain how OSA facilitates seizures. This case suggests that OSA may Table 1 Comparison between obstructive sleep apneas with and without generalized spike and wave discharges. a
Apnea duration (s) K complexes (n/total) Micro-arousals (n/total) Micro-arousal duration (s) a b
b
OSA+ (n = 6)
OSA
22.5 6 6/6 6/6 6.8 0.7
18.5 3.5 0/30 6/30 2.1 0.7
(n = 30)
p 0.14 <0.001 0.048 0.004
Obstructive sleep apneas with generalized spike and wave discharge. Obstructive sleep apneas without generalized spike and wave discharge.
provoke generalized interictal discharges via the combination of K-complex and micro-arousal. This finding recalls the excitatory role we recently assigned to K-complexes in triggering seizures in autosomal dominant nocturnal frontal lobe epilepsy probably by inducing neuronal synchrony across wide cortical territories. Here, K-complexes are associated with generalized interictal activities but not with seizures. Yet ictal and interictal epileptic events were both found to be frequently related to microarousal or arousal during or after OSA, so at the sleep–wake transition. This could be the main factor of the tight relation between OSA and epileptic events. Alternatively, oxygen desaturation has been related to nocturnal seizures in conditions such as central hypoventilation.3 However, in our patient, OSA can trigger seizures and generalized S-W without oxygen desaturation. This supports the suggestion that oxygen desaturation during OSA may not be a major factor exacerbating seizures because of the lack of severe sleep oxygen desaturation.4 Furthermore, both seizures and S-W discharges, absent before, relapsed early after CPAP interruption suggesting that they are both not related to chronic sleep deprivation. CPAP is an effective therapy for OSA and sleep fragmentation, and may strongly reduce seizure frequency and abolish generalized S-W discharges. In conclusion for this case report, OSA induces direct proepileptic actions likely through sleep–wake transitions.
Conflict of interest statement None declared. Acknowledgements We would like to thank Richard Miles for critical reading of the manuscript. This study was supported by the program ‘‘Investissements d’avenir’’ ANR-10-IAIHU-06. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.seizure.2014.09.004.
V.-H. Nguyen-Michel et al. / Seizure 24 (2015) 121–123
References 1. Malow BA, Levy K, Maturen K, Bowes R. Obstructive sleep apnea is common in medically refractory epilepsy patients. Neurology 2000;55:1002–7. 2. Wyler AR, Weymuller Jr EA. Epilepsy complicated by sleep apnea. Ann Neurol 1981;9:403–4.
123
3. Devinsky O, Ehrenberg B, Barthlen GM, Abramson HS, Luciano D. Epilepsy and sleep apnea syndrome. Neurology 1994;44:2060–4. 4. Vaughn BV, D’Cruz OF, Beach R, Messenheimer JA. Improvement of epileptic seizure control with treatment of obstructive sleep apnoea. Seizure 1996;5: 73–8.
Contents lists available at ScienceDirect
Seizure journal homepage: www.elsevier.com/locate/yseiz
Clinical letter
How are epileptic events linked to obstructive sleep apneas in epilepsy? Vi-Huong Nguyen-Michel, Olivier Pallanca, Vincent Navarro, Sophie Dupont, Michel Baulac, Claude Adam * Epileptology Unit, Department of Neurology and Clinical Neurophysiology, Assistance Publique-Hoˆpitaux de Paris, Groupe hospitalier Pitie´-Salpeˆtrie`re and UPMC University Paris 06, CRICM (CNRS UMR-7225), 47-83 Boulevard de L’Hoˆpital, 75651 Paris cedex, France
A R T I C L E I N F O
Article history: Received 24 June 2014 Received in revised form 4 September 2014 Accepted 6 September 2014
1. Introduction Obstructive sleep apnea (OSA) is common in patients with refractory epilepsy and may exacerbate seizures. In epileptic patients with OSA, seizures occur more frequently during sleep.1 Seizure frequency may be reduced by treating OSA2–4 and increase if the treatment is interrupted or neglected.2,3 It is not clear how OSA provokes seizures. Multiple seizureprovoking factors including cerebral hypoxemia, sleep deprivation and sleep fragmentation1 might be involved. The temporal link between OSA and seizures or interictal events might be better understood with careful analysis of video EEG (vEEG) records. Such data has never been precisely reported. We report here a direct relation between OSA and both ictal and interictal epileptic events during vEEG investigations in a patient with temporal lobe epilepsy.
2. Case presentation A 43-year-old woman was admitted to the Epileptology unit for diagnostic purposes. She suffered from refractory post-traumatic epilepsy and experienced daytime partial and nocturnal secondarily generalized seizures. Cerebral MRI revealed no specific signs. FDG-PET showed a left temporal hypometabolism. Additionally, she was obese (body mass index 44 kg/m2) and experienced daytime sleepiness (Epworth score 18).
* Corresponding author at: Unite´ d’Epileptologie, Service de Neurologie 1, Clinique P. Castaigne, Hoˆpital de La Pitie´-Salpeˆtrie`re, 47-83 Boulevard de L’Hoˆpital, 75651 Paris cedex 13, France. E-mail address: [email protected] (C. Adam).
Ventilatory polygraphy investigation revealed a severe OSA syndrome (apnea hypopnea index (AHI) of 75/h). The mean oxygen saturation was 95%, the nadir 72% and the mean decline during apnea was 7%. A seven day vEEG monitoring investigation showed: (i) Incessant OSA consisting of loud snoring during sleep, which was interrupted by a silence, accompanied by visible abdominal efforts and ending in a loud, harsh, stridulous gasp and awakening. (ii) Frequent left temporal lobe spikes (Fig. 1 in supplementary material). (iii) Twelve left temporal lobe seizures consisted in oro-bucal automatisms followed by right-sided motor symptoms and sometimes secondary generalization. Seizures often occurred during sleep (11/12, 92%). Seven of these eleven seizures were associated with OSA (63%): one occurred during OSA without K complex or arousal, six during an awakening EEG activity either immediately (n = 4) or at 12 s and 65 s after an OSA. The remaining four seizures were preceded neither by OSA nor by arousal. (iv) Six 1.5–2.5 Hz symmetrical generalized high-amplitude spikewave (S-W) discharges each occurred during an OSA. They were prominent over anterior regions and formed part of a stereotyped electro-clinical sequence. Breathing stopped leading to a micro-arousal of 6.8 0.7 s (mean standard deviation) comprising a K complex and succeeding alpha run. This was followed by a S-W discharge of duration 10 4 s and terminated by a loud stridulous gasp and awakening (Fig. 1). These S-W discharges began about 10 s after the onset of the OSA and terminated about 2.5 s before (n = 4), or at the end of the OSA (n = 2). Discharges were generalized throughout, with an initial spike occurring sometimes slightly in advance in the left temporal region (n = 3). Compared with 30 successive isolated and randomly-chosen OSA episodes without generalized epileptic discharges, those preceding EEG discharges were more often associated with a micro-arousal (p = 0.048) of longer duration (p = 0.004) (Fischer Exact and Mann–Whitney test) (Table 1). (v) Sleep was very fragmented without deep and rapid eye movements sleep. The patient was treated with continuous positive airway pressure (CPAP). The rate of AHI decreased to 5/h (indicated by
http://dx.doi.org/10.1016/j.seizure.2014.09.004 1059-1311/ß 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
V.-H. Nguyen-Michel et al. / Seizure 24 (2015) 121–123
122
Fig. 1. Electro-clinical sequence of obstructive sleep apnea inducing unexpected generalized spike-wave discharge.
the CPAP machine) and seizure frequency decreased by 60%. One year later, a vEEG performed under CPAP and oxymetry showed normal sleep structure and normal oxygen saturation. When the patient voluntarily interrupted CPAP, she immediately experienced again incessant OSA, one typical left temporal lobe seizure and one generalized S-W discharge which were both OSA-related and without oxygen desaturation (Figs. 2 and 3 in supplementary material). 3. Discussion A link between OSA and epilepsy has been previously suggested.1–4 In this patient we describe the precise temporal link between the OSA and the epileptic events. We found seizures are often preceded by an OSA, reduced under CPAP and re-emerge immediately when CPAP is withdrawn. We also found an unexpected interictal EEG pattern of rhythmic generalized S-W discharges strictly related to OSA, disappearing under CPAP, and re-emerging after CPAP arrest. This interictal pattern has not been previously published and is likely the result of a secondary bilateral synchrony (i.e. a bilateral synchronous discharge arising from a unilateral epileptic focus) and is not of a primary generalized origin (indeed there was no suggestive clinical history and no spontaneous generalized discharges during two prolonged monitorings). This also differs completely from electro-clinical consequences of severe hypoxic cerebral damage with continuous pseudo-periodic S-W on a degraded background activity. Multiple hypotheses including cerebral hypoxemia, sleep deprivation or fragmentation1 have been advanced to explain how OSA facilitates seizures. This case suggests that OSA may Table 1 Comparison between obstructive sleep apneas with and without generalized spike and wave discharges. a
Apnea duration (s) K complexes (n/total) Micro-arousals (n/total) Micro-arousal duration (s) a b
b
OSA+ (n = 6)
OSA
22.5 6 6/6 6/6 6.8 0.7
18.5 3.5 0/30 6/30 2.1 0.7
(n = 30)
p 0.14 <0.001 0.048 0.004
Obstructive sleep apneas with generalized spike and wave discharge. Obstructive sleep apneas without generalized spike and wave discharge.
provoke generalized interictal discharges via the combination of K-complex and micro-arousal. This finding recalls the excitatory role we recently assigned to K-complexes in triggering seizures in autosomal dominant nocturnal frontal lobe epilepsy probably by inducing neuronal synchrony across wide cortical territories. Here, K-complexes are associated with generalized interictal activities but not with seizures. Yet ictal and interictal epileptic events were both found to be frequently related to microarousal or arousal during or after OSA, so at the sleep–wake transition. This could be the main factor of the tight relation between OSA and epileptic events. Alternatively, oxygen desaturation has been related to nocturnal seizures in conditions such as central hypoventilation.3 However, in our patient, OSA can trigger seizures and generalized S-W without oxygen desaturation. This supports the suggestion that oxygen desaturation during OSA may not be a major factor exacerbating seizures because of the lack of severe sleep oxygen desaturation.4 Furthermore, both seizures and S-W discharges, absent before, relapsed early after CPAP interruption suggesting that they are both not related to chronic sleep deprivation. CPAP is an effective therapy for OSA and sleep fragmentation, and may strongly reduce seizure frequency and abolish generalized S-W discharges. In conclusion for this case report, OSA induces direct proepileptic actions likely through sleep–wake transitions.
Conflict of interest statement None declared. Acknowledgements We would like to thank Richard Miles for critical reading of the manuscript. This study was supported by the program ‘‘Investissements d’avenir’’ ANR-10-IAIHU-06. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.seizure.2014.09.004.
V.-H. Nguyen-Michel et al. / Seizure 24 (2015) 121–123
References 1. Malow BA, Levy K, Maturen K, Bowes R. Obstructive sleep apnea is common in medically refractory epilepsy patients. Neurology 2000;55:1002–7. 2. Wyler AR, Weymuller Jr EA. Epilepsy complicated by sleep apnea. Ann Neurol 1981;9:403–4.
123
3. Devinsky O, Ehrenberg B, Barthlen GM, Abramson HS, Luciano D. Epilepsy and sleep apnea syndrome. Neurology 1994;44:2060–4. 4. Vaughn BV, D’Cruz OF, Beach R, Messenheimer JA. Improvement of epileptic seizure control with treatment of obstructive sleep apnoea. Seizure 1996;5: 73–8.