A brainstem inflammatory lesion causing REM sleep behavior disorder and sleepwalking (parasomnia overlap disorder)
Article Outline
Abstract
A 40-year-old woman with no prior parasomnia developed an acute inflammatory rhombencephalitis with multiple cranial nerve palsies and cerebellar ataxia, followed by myelitis 6
months later, and by an intracranial thrombophlebitis 1month after. Between and after these episodes, she had a persistent, mild right internuclear ophtalmoplegia, a mild cerebellar ataxia, and a severe REM sleep behavior disorder (RBD) lasting for 2years. She talked, sang and moved nightly while asleep, and injured her son (cosleeping with her) while asleep. In addition, she walked asleep nightly. During video-polysomnography, there were two arousals during slow wave sleep without abnormal behavior, while 44% of REM sleep was without chin muscle atonia with bilateral arm and leg movements. There were small hypointensities in the right pontine tegmentum and in the right dorsal medulla on T1-weighted magnetic resonance imaging, suggesting post-inflammatory lesions that persisted between acute episodes. The RBD and sleepwalking did not improve with clonazepam, but improved with melatonin 9mg/d. The unilateral small lesion of the pontine tegmentum could be responsible for the parasomnia overlap disorder as in other rare lesional cases.
Keywords: REM sleep behavior disorder, Brainstem lesion, Demyelinating diseases of the nervous system, Melatonin, Parasomnia overlap disorder, Sleepwalking
1. Introduction
REM sleep behavior disorder (RBD) is defined by enacted, violent dreams during sleep, associated with the loss of normal chin muscle atonia or visible complex behaviors during REM sleep [1]. In rare patients suffering from the parasomnia overlap disorder [1], RBD is combined with a disorder of arousal (sleepwalking or sleep terrors). RBD and parasomnia overlap disorder are mostly associated with neurodegenerative diseases [2], [3], but they are also idiopathic or observed in some rare patients with focal lesions of the brainstem, psychiatric disorders, nocturnal cardiac arrhythmia, narcolepsy, Moebius syndrome and spinocerebellar ataxia [2], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13]. We report a patient suffering from an enigmatic, inflammatory disease of the central nervous system with persistent parasomnia overlap disorder, emerging with a pontine and medulla lesion.
2. Case report
A 40-year-old woman with unremarkable family and personal medical history, free from any medication, developed acute rhombencephalitis. She had cerebellar ataxia and cranial nerves palsy, including a facial palsy, diplopia, right hearing loss, dysphagia and dysarthria. In addition, she reported vivid dreams associated with vigorous movements while asleep. On examination, she had right third, fifth, sixth, seventh, eighth, ninth and tenth nerve palsies (with laryngeal hemiparesis), plus a right internuclear ophtalmoplegia, and a static cerebellar ataxia. On the brain magnetic resonance imaging (MRI), there were gadolinium-enhanced hyperintense signals on T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences and hypointense signals on T1-weighted sequences in the mesencephalic tegmentum, the fourth ventricle floor and the right medulla, suggesting diffuse inflammatory lesions. Cerebro-spinal fluid contained 8 white blood cells/mcL; the protein levels were normal (0.25g/L), as were the interferon alpha levels, and there was no intratechal synthesis of immunoglobulin. Tests for autoimmune diseases, infection, sarcoïdosis, vasculitis, epilepsy and multiple sclerosis were negative, but there was an elevated serum erythrocyte sedimentation rate (ESR) at 33mm/h (normal value is lower than 20mm/h). The neuromyelitis optica and paraneoplastic antineuronal antibodies were negative. As the lesions were inflammatory, the patient was treated with a high-dose of corticosteroids. She recovered within 5weeks, except for the cerebellar ataxia and the anterior internuclear ophtalmoplegia, and had only hypointensities on T1-weighted images in the right pontine tegmentum and medulla.
Six months after the episode, she developed an acute C2-7 and D5-6 myelitis. Extensive tests were normal except for an elevated ESR (50mm/h). She was treated with oral corticosteroids with rapid benefit. One month later she developed a cerebral thrombophlebitis. Spinal fluid analysis, immunological, inflammatory tests and investigations for thrombophilia were again negative. Symptoms disappeared with anticoagulation treatment.
The patient was followed up during 2years. She had a mild internuclear ophtalmoplegia, a cerebellar ataxia and abnormal sleep behaviors. Psychiatric and neuropsychological evaluations were normal. The brain and spinal MRI were unchanged, with a small, persistent hypointensity in the right pontine tegmentum (Fig. 1A) and in the dorsal right medulla on T1 sequence and hyperintensity on T2-FLAIR sequences (Fig. 1B). As for the violent sleep behaviors, she had no personal or family history of parasomnia. Her sister and son reported that she would speak, sing, have arm and leg jerks, and walk several times per night, every night while asleep. She opened doors, walked into the kitchen or her son’s room, did not hurt herself and had no recall of any associated mental content. She slapped her son (cosleeping with her), while she was dreaming of giving him a spanking. She woke up after the violent behaviors or if she happened to sing out too loudly. She could hardly remember the episodes the next morning but felt tired on awakening. She did not complain of sleepiness and hallucinations. One year after the first neurological episode, she underwent a video-polysomnography. She slept 4h without periodic leg movements or sleep apnea. The episodes of slow wave sleep were interrupted by sudden arousals (Fig. 2) without any abnormal movement. This feature, associated with nightly-recurrent, quiet, sleep-associated walking episodes without dream recall was suggestive of sleepwalking as an arousal disorder rather than as a REM sleep behavior disorder. REM sleep lasted 90min (39% of total sleep time, when 17–23% is expected). There was enhanced chin muscle tone during 44% of REM sleep and increased phasic leg muscle activity (Fig. 3). On video (Supplemental data) she spoke, mumbled, held up her neck and displayed complex hand movements (looking like writing and eating), arm flailing and leg jerking. There was no epileptiform activity during sleep. The mean sleep latency during the multiple sleep latency test was 18.6min with no sleep onset in REM period. Clonazepam 2mg/night was prescribed for 8months. As it was not beneficial, she received melatonin. Only a 9mg melatonin dose, prescribed during 1year, partially improved the frequency and severity (from several events per night, to one event per week) of RBD and sleepwalking.
Fig. 1.
(A) Axial T1-weighted brain MRI of the patient between neurological episodes showing hyperintensities in the pontine tegmentum. (B) Axial T2 FLAIR-weighted brain MRI showing hypointensities in the pontine tegmentum. (C) Superior axial section of the brainstem reproduced with permission from [15], at the same level as the MRI images of the patient, when the path of the 3rd and 4th cranial nerves is horizontal. No 20: medial longitudinal fasciculus; No 21: superior cerebellar peduncle; No 22: IVth ventricle; No 23: coeruleus nucleus, No 24: mesencephalic nucleus of trigeminal nerve; No 25: tentorum of cerebellum.
Fig. 2.
Night-time hypnogram of the patient with parasomnia overlap disorder, showing two awakenings during slow-wave sleep. The x-axis displays the time, the y-axis displays the sleep–wake stages, with REM, Rapid eye movement sleep; W, wakefulness.
Fig. 3.
An example of an 1 min-period of REM sleep without atonia in the patient, with enhanced tonic chin muscle tone during REM sleep. The montage includes, from top to bottom, EEG (Fp1-A2 , C3-A2, C3-01), right and left electrooculograms, chin electromyogram, left and right tibialis anterior electromyogram, pulse, thoracic and abdominal breathing efforts, airflow and EKG.
3. Discussion
This patient had a nightly-recurring parasomnia overlap disorder, secondary to a recurrent inflammatory disease of the brainstem and spinal cord of unknown origin (but not multiple sclerosis). We attributed the parasomnia to the small right lesions in the pontine tegmentum and in the medulla, as they were the single persistent lesions between episodes. Here the pontine lesion was small and contained medial longitudinal fasciculus (as she had a right internuclear ophtalmoplegia) and superior cerebellar peduncle (as she had a cerebellar ataxia). The lesion probably encompassed the coeruleus and subcoeruleus nuclei which are located between these two structures, close to the fourth ventricle. Lesions of the subcoeruleus nucleus can elicit RBD in rats and cats [14]. There is, however, no animal model of sleepwalking or parasomnia overlap disorder. Nine previous RBD cases were associated with lesions of the brainstem of various origin (vascular disease, inflammation, tumor). The lesions were mostly dorsal, median, and located from the mesencephalon to the lower/mid pontine tegmentum, and in one case in the medulla (Table 1). Of interest, our patient and four previously published patients had an unilateral lesion while the RBD movements were bilateral [4], [6], [8], [10]. These observations suggest that unilateral lesion of the REM sleep atonia system is sufficient to enhance/release the axial and bilateral limb muscle tone during REM sleep but also to trigger sleepwalking. Of interest, melatonin (but not clonazepam, while it benefits in other cases) improved the parasomnia overlap disorder here, even though it was lesional. Melatonin is an efficacious therapy in RBD [16] but was also beneficial in a child with sleepwalking [17]. Two other patients with brainstem lesions displayed parasomnia overlap disorder (Table 1). Eventually, status dissociatus, which is the most dissociate state of REM-non REM sleep stages, had been described in two patients with brainstem lesions [12], [13]. The damaged brainstem structures may contain motor systems that are disinhibited both during non REM and REM sleep.
Table 1. Type, location and neurological signs in focal lesions of the brainstem associated with REM sleep behavior disorders, parasomnia overlap syndrome and status dissociatus.
| Case no. | Authors | Type of lesion | Location of her lesion | Other neurologic symptoms |
|---|---|---|---|---|
| REM sleep behavior disorder | ||||
| 1 | Kimura et al. [4] | Ischemic infarct | Left upper pons | Episode of transient dizziness and weakness in the right upper and lower extremities |
| 2 | Plazzi et al. [5] | Multiple sclerosis | Pons | No other sign |
| 3 | Zambelis et al. [6] | Neurinoma | Left pontocerebellar angle | Deafness on the left side |
| 4 | Tippmann-Peikert et al. [7] | Multiple sclerosis | Dorsal pons | Acute vertigo, ataxia, diplopia, dysarthria, bifacial weakness |
| 5 | Iranzo et al. [8] | Acute hemorrhage from a cavernous hemangioma | Left medulla | Wallenberg syndrome |
| 6 | Mathis et al. [9] | Inflammatory | Dorsomedial pontine tegmentum | Sleep onset in REM periods |
| 7 | Xi et al. [10] | Ischemic infarct | Right paramedian pons | None |
| 8 | Gomez-Choco et al. [11] | Multiple sclerosis | Pons | Not available |
| Parasomnia overlap syndrome | ||||
| 1 | Schenck et al. [3] | Multiple sclerosis | Not available | Not available |
| 2 | Schenck et al. [3] | Astrocytoma | Fourth ventricle | Not available |
| Status dissociatus | ||||
| 1 | Provini et al. [13] | Cavernoma | Pontomesenphalic tegmentum | Headache, diplopia, enuresis, vertical nystagmus, dysarthria, dysmetria, ataxia |
| 2 | Condurso et al. [12] | Multilacunar state | Basal ganglia, internal capsula, paratrigona and median pons | Romberg sign, left hemianopsia, spastic hemiparesis and dysmetria |
These case reports provide evidence that lesions within or near the pontine tegmentum are associated with human RBD and parasomnia overlap disorder and that a unilateral lesion by itself is sufficient to cause RBD and sleepwalking.
Appendix A. Supplementary data
Supplementary video.
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PII: S1389-9457(09)00007-0
doi:10.1016/j.sleep.2008.12.006
© 2009 Elsevier B.V. All rights reserved.
