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Case Report
Somnolence and Periodic Limb Movements Due to Treatment with Baclofen
Muhammad Najjar *
Department of Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois, Chicago, USA Received: 21 Nov. 2019 Accepted: 18 Jan. 2020
Abstract
Background and Objective: Excessive sleepiness is a common reason for a referral to sleep medicine clinics. The clin- ical picture and context usually suggest the underlying cause; however, all possibilities should be considered and only after sleep studies are done, one can determine the likely cause of the patient’s symptoms.
Case Report: We presented the case of a man who was referred for evaluation of hypersomnolence along with snoring and possible apnea during sleep. Obstructive sleep apnea (OSA) was suspected, so home sleep apnea test (HSAT) and later poly- somnography (PSG) were performed and both ruled out this possibility. The PSG showed frequent periodic limb movements (PLMs), some associated with arousal; abnormal sleep structure suggested the effect of medication. The patient had been tak- ing baclofen for musculoskeletal pain and it was concluded that baclofen was the cause of the patient’s somnolence and PLMs. The patient’s clinical presentation was compounded by his history of post-traumatic stress disorder (PTSD) and gas- troesophageal reflux which probably caused increased arousals and the subjective feeling of poor sleep quality.
Conclusion: Treatment with medications that have sedative effects should be considered in all patients presenting with excessive daytime sleepiness even if the initial clinical picture suggests another possible cause. Baclofen can cause PLMs, sedation, changes in N3 stage, and reduction in rapid eye movement (REM) sleep.
© 2020 Tehran University of Medical Sciences. All rights reserved.
Keywords: Baclofen; Disorders of excessive somnolence; Nocturnal myoclonus syndrome
Citation: Najjar M. Somnolence and Periodic Limb Movements Due to Treatment with Baclofen. J Sleep Sci 2020; 5(2): 73-76.
Introduction1
Hypersomnolence is a common complaint in sleep medicine clinics. It is frequently due to sleep- disordered breathing (SDB), central hypersomnia, circadian rhythm disorders as well as many other sleep disorders. Sometimes a patient has multiple possible explanations and it may be difficult to de- termine initially which one is the main cause of the patient’s complaint and all need to be addressed to result in significant clinical improvement. In the case discussed below, we present a case of a man with excessive daytime sleepiness and highlight how multiple factors might have contributed to his
* 1Corresponding author: M. Najjar, Department of Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois, Chicago, USA
Tel: +1 312 3551091, Fax: +1 312 4130503 Email: [email protected]
complaint and how considering these factors helped explain the findings of his polysomnogra- phy (PSG), all in the context of his clinical history.
Case Report
A 56-year-old man presented with snoring, nocturnal choking, non-refreshing sleep, and day- time somnolence. He denied morning headaches, sleep paralysis, cataplexy, and discomfort in his legs or an urge to move them in the evening. He would typically sleep from 11:00 PM to 5:30 AM on weekdays and weekends, and his sleep sched- ule did not change in many years.
He had history of degenerative joint disease of the lumbosacral spine and knees, right biceps pain due to tendinitis, gastroesophageal reflux, hy- pogonadism, erectile dysfunction (ED), and post-
Somnolence and PLMs Due to Baclofen
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not taking his prescribed treatment.
His medications included: baclofen 10 mg oral- ly 3 times a day, omeprazole 40 mg twice a day, tadalafil 20 mg when needed, and testosterone 200 mg intramuscularly (IM) every 2 weeks.
His Epworth Sleepiness Scale (ESS) score was 15, body mass index (BMI) was 27 kg/m2, and upper airway was Mallampati class II. His vital signs were normal and general medical examina- tion was unremarkable except for musculoskeletal tenderness in the right shoulder. Laboratory eval- uation showed normal renal function tests, iron studies, and vitamin and hormonal levels.
Prior to presenting to sleep medicine service, he had a home sleep apnea test (HSAT) that was reported as normal. A PSG was performed and showed the findings in table 1:
Table 1.Polysomnographic (PSG) findings
Parameter Value
Total sleep time (minute) 352.0
Sleep efficiency (%) 88.0
Waking after sleep onset (minute) 44.1
TAI (/hour) 66.5
SOL (minute) 4.0
REM sleep latency (minute) 386.0
N1 stage (%) 40.5
N2 stage (%) 56.0
N3 stage (%) 1.1
REM stage (%) 2.4
AHI (/hour) 1.7
Minimum oxygen saturation (%) 89.0
PLMI (/hour) 91.2
PLM-arousal index (/hour) 43.5
TAI: Total arousal index; SOL: Sleep onset latency; REM: Rapid eye movement; AHI: Apnea-hypopnea index; PLMI: Periodic limb movement index; PLM: Periodic limb movement
Hypnogram of his sleep study showed reduc- tion in rapid eye movement (REM) sleep and stage N3, frequent periodic limb movements (PLMs), frequent arousals, and absence of sleep
apnea (Figure 1).
Figure 2 shows PLMs, some of them are asso- ciated with arousal.
Discussion
Although the patient’s history is suggestive of obstructive sleep apnea (OSA), his HSAT and PSG clearly ruled out this possibility. Snoring is not unusual in patients who do not have sleep ap- nea; these patients have primary snoring. The pa- tient’s reported nocturnal choking could be due to acid reflux or exaggerated reaction to rare apneas in a patient with hyperarousal related to PTSD.
His PSG shows a significant number of PLMs and given that a significant number of them is associated with arousal, it is possible that his somnolence and disrupted sleep are due to period- ic limb movement disorder (PLMD). However, it is also possible that both hypersomnolence and increased PLMs are due to treatment with baclo- fen. It has been reported that baclofen can in- crease PLMs (1) and it is known to cause sleepi- ness. The patient was questioned about the onset of his hypersomnolence and history suggested that it started after baclofen was prescribed for him.
The patient’s PSG data show increased stage N1, minimal stage N3 and REM sleep, and in- creased REM latency. These findings raise the possibility of the effect of baclofen which can ex- plain some but not all of these findings. It was reported that baclofen could decrease REM stage sleep especially with high doses, increase stage N3, increase total sleep time, and decrease sleep latency. It can also increase the number of PLMs and decrease arousals induced by the leg move- ments (1-4).
It has also been reported that baclofen can pro- duce a minor reduction of oxygen saturation dur- ing sleep (2) and can also induce central sleep ap- nea (CSA) (5).
Figure 1. Hypnogram summarizing ploysmonographic (PSG) findings
M. Najjar
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The patient’s history of PTSD raises the possi- bility that some features of his sleep structure and PSG findings are due to PTSD. PTSD is known to cause sleep disturbances including insomnia, nightmares, hyperarousal, and trauma-associated sleep disorder (TSD) (6); however, despite signif- icant subjective complaints related to sleep, PTSD does not seem to induce major objective changes in sleep structure (7). The increase in arousal in- dex is likely due to PTSD which causes adrener- gic hyperactivity in the locus coeruleus (LC).
Central hypersomnia is a possible explanation for the patient’s symptoms; however, the abnor- malities of his sleep structure are not consistent with it although they do not rule it out. In addition, the effect of medication with sedative features should be considered before pursuing this possibil- ity. If a patient has narcolepsy, would the use of a nighttime dose of baclofen help alleviate sleepiness or not? The literature is not consistent in this re- gard. One report indicated that baclofen did not help control sleepiness in narcoleptic patients (8), and another one showed that baclofen was effective in treating excessive sleepiness in narcoleptics and suggested that higher doses might need to be used along with other treatments for narcolepsy (9).
Sleep deprivation should be considered in pa- tients presenting with somnolence, especially in patients who are busy and their daily schedule does not allow them to get adequate sleep as they work long hours, go to school, and have family responsibilities. These patients tend to get sleepier and sleepier as the week progresses and have longer sleep hours on weekends compared to weekdays. Most of them recognize that they do not get adequate sleep and do not need to see
sleep clinicians; however, some will seek help if they also have another cause for their sleepiness.
Conclusion
The most likely cause of the patient’s sleepi- ness is either sedation due to treatment with bac- lofen or PLMD.
The findings of the patient’s sleep structure are likely due to baclofen although PTSD acid reflux and shoulder pain may also contribute to in- creased arousal index and disrupted sleep.
The patient was advised to stop taking baclo- fen, and see pain specialist for alternative treat- ment of his musculoskeletal condition. He report- ed later that his symptoms improved significantly.
He was satisfied and did not wish to pursue fur- ther work-up. We were unable to repeat his PSG as it was against his wish.
Conflict of Interests
Authors have no conflict of interests.
Acknowledgments
The author is indebted to Ms. Rama Najjar for her assistance in preparing the manuscript.
References
1. Guilleminault C, Flagg W. Effect of baclofen on sleep-related periodic leg movements. Ann Neurol 1984; 15: 234-9.
2. Finnimore AJ, Roebuck M, Sajkov D, et al. The effects of the GABA agonist, baclofen, on sleep and breathing. Eur Respir J 1995; 8: 230-4.
3. Raad S, Wilkerson M, Jones KR, et al. The effect of baclofen on objective and subjective sleep measures
Somnolence and PLMs Due to Baclofen
76 J Sleep Sci, Vol. 5, No. 2, 2020
http://jss.tums.ac.ir in a model of transient insomnia. Sleep Med 2020; 72:
130-4.
4. Vienne J, Lecciso G, Constantinescu I, et al. Dif- ferential effects of sodium oxybate and baclofen on EEG, sleep, neurobehavioral performance, and memory. Sleep 2012; 35: 1071-83.
5. Olivier PY, Joyeux-Faure M, Gentina T, et al. Severe central sleep apnea associated with chronic baclofen therapy: A case series. Chest 2016; 149: e127-e131.
6. Mysliwiec V, O'Reilly B, Polchinski J, et al. Trau- ma associated sleep disorder: A proposed parasomnia encompassing disruptive nocturnal behaviors, night-
mares, and REM without atonia in trauma survivors. J Clin Sleep Med 2014; 10: 1143-8.
7. Germain A. Sleep disturbances as the hallmark of PTSD: Where are we now? Am J Psychiatry 2013;
170: 372-82.
8. Huang YS, Guilleminault C. Narcolepsy: Action of two gamma-aminobutyric acid type B agonists, baclo- fen and sodium oxybate. Pediatr Neurol 2009; 41: 9- 16.
9. Morse AM, Kelly-Pieper K, Kothare SV. Manage- ment of excessive daytime sleepiness in narcolepsy with baclofen. Pediatr Neurol 2019; 93: 39-42.