Elsevier

Sleep Medicine

Volume 8, Issue 1, January 2007, Pages 60-64
Sleep Medicine

Original article
Insights into REM sleep behavior disorder pathophysiology in brainstem-predominant Lewy body disease

https://doi.org/10.1016/j.sleep.2006.08.017Get rights and content

Abstract

Background and purpose:

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia reflecting changes in the brain, but which specific neuronal networks are involved in human RBD pathogenesis has not yet been determined. To date, only one case of idiopathic RBD has undergone autopsy, in which “incidental Lewy body disease” was found. Due to the severe neuronal loss and gliosis in the substantia nigra (SN) and locus ceruleus (LC) in this case, degeneration of brainstem monoaminergic neurons was postulated as the underlying substrate for RBD. Additional cases of idiopathic RBD with neuropathologic examination may help clarify which key brainstem structures are involved.

Patient and methods:

Case report with neuropathologic analysis.

Results:

A man with polysomnographically proven RBD (onset age 57 years), but no other neurologic signs or symptoms, underwent neuropathologic examination upon his death at age 72. Histopathologic analysis showed Lewy body disease, but no significant neuronal loss or gliosis was present in the SN or LC.

Conclusions:

This case represents another example of Lewy body disease associated with RBD. The minimal degenerative changes in the SN and LC call into question the role of these nuclei in RBD, at least in our case. We suggest additional cases of idiopathic RBD undergo neuropathologic analyses to better delineate the neurologic substrate of this intriguing parasomnia.

Introduction

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by loss of normal skeletal muscle atonia during REM sleep with prominent motor activity and dreaming [1], [2]. There is ample data from animal and human studies that dysfunction of brainstem structures and networks are likely involved, but which specific neuronal networks are involved in RBD pathogenesis has not yet been determined [1], [3]. To date, fewer than 25 cases of polysomnographically (PSG) proven RBD cases have undergone neuropathologic examination [3], and only one case of idiopathic RBD has undergone autopsy, in which “incidental Lewy body disease” was found [4]. We report herein another case of idiopathic RBD associated with Lewy body disease (LBD), but with degenerative changes topographically different from those previously reported.

Section snippets

Subject and methods

The patient was followed longitudinally at Mayo Clinic Rochester, and written consent was provided for autopsy. Evaluation of antemortem and pathologic data for research purposes on patients with RBD has also been approved by the Mayo Foundation Institutional Review Board.

All available clinical, laboratory, and PSG data were analyzed and summarized. PSG included surface electromyographic (EMG) monitoring of the submental, anterior tibial, and wrist extensor muscles. Neuropathologic examination

Antemortem features

This right-handed retired male physician began exhibiting dream enactment behavior at the age of 57. His wife observed numerous episodes of flailing and thrashing his limbs while vocalizing. She had been struck and bitten several times. The patient would describe the dreams associated with this activity as nightmares in which he was being chased or attacked, and he bolted out of bed on several occasions while attempting to evade the attackers. The frequency and severity of these episodes

Discussion

RBD has been associated with several etiologies, including medications, autoimmune/limbic encephalitis, narcolepsy, structural lesions in the brainstem, and neurodegenerative disease [1], [2], [9], [10], [11]. The few cases which have been studied with magnetic resonance imaging (MRI) have shown lesions in the dorsal pons [10], [11], yet the specific neuronal networks involved in human RBD pathogenesis have not been identified with certainty. Although ubiquitin and α-synuclein

Acknowledgment

This study was supported by Grants P50 NS40256, P50 AG16574, and RO1 AG15866.

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