Unrecognized sleep‐related hypermotor epilepsy emerging in a patient with REM sleep behavior disorder: A case report

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by loss of muscle atonia during REM sleep, leading to dream enactment behaviors. ¹ Sleep‐related hypermotor epilepsy (SHE) involves stereotyped focal seizures occurring predominantly during non‐REM sleep. ² Although both present with abnormal sleep‐related movements, distinguishing them is essential because treatment differs. We report a case of overlooked SHE during treatment for RBD.

A 61‐year‐old man was referred to our outpatient clinic for stereotyped movements and nocturnal wandering. He had developed depression 3 years previously and was prescribed mirtazapine 30 mg daily, which was increased to 45 mg after 6 months. Following the dose increase, non‐periodic, non‐stereotyped movements of the limbs and trunk emerged during sleep. Two years before presentation, he was diagnosed with RBD at another hospital and was prescribed clonazepam 1 mg and Yokukansan 5 g daily. He was also diagnosed with obstructive sleep apnea and started continuous positive airway pressure therapy, with good adherence. Thereafter, his non‐stereotyped movements improved but still occurred occasionally. However, 1 year later, his nocturnal symptoms worsened despite continued treatment and were now associated with falling out of bed. One month before presentation, he developed nocturnal wandering without recollection and did not awaken even when shaken by his wife. Mirtazapine had been discontinued because it was suspected of having contributed to the worsening of his symptoms. Detailed questioning revealed newer stereotyped episodes consisting of groaning and flapping movements of the right upper limb, followed by bilateral but predominantly right‐sided flexion–extension movements of the knees; these were clearly distinct from his prior non‐stereotyped movements. Suspecting epilepsy, we performed a 5‐day inpatient evaluation with long‐term video electroencephalography monitoring (LTVEM) and polysomnography.

His neurological examination was unremarkable, and no depressive symptoms were observed. His Mini‐Mental State Examination, Patient Health Questionnaire‐9, and RBD Screening Questionnaire scores were 30, 3, and 8, respectively. Brain magnetic resonance imaging, dopamine transporter scan, and ¹²³I‐metaiodobenzylguanidine scintigraphy were normal. Polysomnography (detailed findings in Data S1) showed REM sleep without atonia (RWA). LTVEM captured multiple stereotyped motor episodes during non‐REM sleep with similar semiology, accompanied by rhythmic slow waves predominantly over the left temporal region (Fig. 1 and Fig. S1). No epileptiform discharges were observed during the interictal period (Fig. S2). Additionally, non‐stereotyped motor episodes without epileptiform discharges were observed during REM sleep (Fig. S3). Taken together, these findings supported the diagnosis of RBD and were clinically compatible with SHE according to diagnostic criteria. ³ Although not captured on LTVEM, the nocturnal wandering lasted longer than typical seizures, whereas recorded seizures were brief motor episodes in bed. Therefore, although this remains uncertain, the wandering was considered more suggestive of postictal confusion than the seizure itself. The stereotyped movements and nocturnal wandering improved after initiation of lacosamide 50 mg daily, and resolved at 100 mg.

Fig. 1.

Long‐term video electroencephalography monitoring (average reference) during non‐rapid eye movement stage 2 captured a stereotyped motor episode consisting of groaning and flapping movements of the right upper limb, followed by flexion–extension movements of both knees, lasting approximately 10 s. The video snapshot corresponds to the time point marked by the green vertical line, at which the movements of the right upper limb and both knees were still ongoing. A burst of slow waves appeared in the left temporal region 15 s after movement onset (red arrows). The black vertical line indicates the end of the motor episode. Similar episodes were recorded seven times during non‐rapid eye movement stage 2 over 2 nights. Yellow vertical lines represent 1‐s intervals. Sensitivity = 10 μV/mm; high‐frequency filter = 50 Hz; low‐frequency filter = 1.6 Hz.

In this case, the patient was initially treated for RBD, but seizures and postictal confusion later emerged and were overlooked. The diagnosis of RBD was supported by improvement of non‐stereotyped nocturnal movements with clonazepam and Yokukansan, RWA on polysomnography, and the observation of REM‐related movements without epileptiform discharges on LTVEM. However, RBD alone could not explain the new stereotyped movements or nocturnal wandering without arousal. RBD symptoms typically fluctuate markedly from night to night, ⁴ and patients are usually easily awakened during episodes. ⁵ These features raised suspicion of seizures and postictal confusion, prompting further evaluation. The diagnosis of SHE was supported by repeated stereotyped movements with rhythmic slow waves during non‐REM sleep on LTVEM, and their resolution with lacosamide. Because the seizure focus and etiology could not be determined, the underlying focal epilepsy remained unclear.

RBD is common in older adults, with a prevalence of approximately 1% in the middle‐aged and older population and 2% in the elderly. ⁵ In contrast, SHE is rare, with a prevalence of 1.8–1.9 per 100,000, ⁶ and typically develops before age 20 years. ³ To our knowledge, the coexistence of RBD and SHE has not been reported. Manni et al. reported coexisting RBD in 10 of 80 patients with epilepsy, including five with predominantly sleep‐related seizures; however, whether these cases represented SHE could not be determined from their report. ⁷ They also included cases in which RBD episodes were misinterpreted as seizures. In another study, RWA was found in 31 of 205 patients with SHE, but none had an RBD episode during polysomnography or a typical history of RBD. ⁸ These findings suggest that the coexistence of RBD and SHE may be uncommon or potentially overlooked. More broadly, RBD should be differentiated from sleep‐related seizures, including SHE. ⁹

In conclusion, RBD may coexist with SHE and can be difficult to distinguish. When patients with RBD show changes or worsening of nocturnal symptoms, careful history taking and, when necessary, evaluation with both polysomnography and LTVEM are important to avoid misdiagnosis.

Author contributions

T.F. conceptualization, literature search, data curation, visualization, and writing (original draft). M.F. conceptualization, project administration, supervision, and writing (review and editing). K.N., S.S. conceptualization and writing (review and editing). M.T. conceptualization, supervision, and writing (review and editing).

Disclosure statement

MF has received honoraria from Eisai. SS has received honoraria from Eisai, Yoshitomi, Tsumura, Otsuka Pharma, Sumitomo Pharma, Lundbeck Merck Sharp & Dohme, Meiji‐Seika Pharma, Takeda Pharma, Miyarisan, and Viatris. MT has received honoraria from Otsuka Pharma, Dainippon Sumitomo Pharma, Tsumura, Lundbeck Merck Sharp & Dohme, Eisai, Meiji‐Seika Pharma, Viatris, Mitsubishi Tanabe, Janssen, Mochida Pharma, and Takeda Pharma. All other authors have no conflicts of interest.

Supporting information

Data S1. Supporting information.

Figure S1. Long‐term video electroencephalography monitoring (longitudinal bipolar montage) during non‐rapid eye movement stage 2 captured the same stereotyped motor episode shown in Fig. 1, which consisted of groaning and flapping movements of the right upper limb, followed by flexion–extension movements of both knees, lasting approximately 10 s. A burst of slow waves appeared in the left temporal region 15 s after movement onset (red arrows). The black vertical line indicates the end of the motor episode. Over two nights, seven similar episodes were recorded: five after 10–20 min of sustained non‐rapid eye movement stage 2, and two shortly after transition from non‐rapid eye movement stage 1 to stage 2. Yellow vertical lines represent 1‐s intervals. Sensitivity = 10 μV/mm; high‐frequency filter = 50 Hz; low‐frequency filter = 1.6 Hz.

Figure S2. Long‐term video electroencephalography monitoring (referential montage) during non‐rapid eye movement stage 1 showing no epileptiform discharges. Yellow vertical lines represent 1‐s intervals. Sensitivity = 10 μV/mm; high‐frequency filter = 60 Hz; low‐frequency filter = 0.53 Hz.

Figure S3. Long‐term video electroencephalography monitoring (average reference) during rapid eye movement sleep captured a non‐stereotyped transient motor episode characterized by irregular limb movements without vocalization, lasting approximately 5 s. No epileptiform discharges were observed before or after the episode. Yellow vertical lines represent 1‐s intervals. Sensitivity = 10 μV/mm; high‐frequency filter = 50 Hz; low‐frequency filter = 1.6 Hz.

Data availability statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.