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

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.

Figure

a.) The dorsal motor nucleus (X) shows mild neuronal loss and gliosis with spheroids containing LBs (arrow). b.) An adjacent section of the dorsal motor nucleus (X) immunostained for α-synuclein shows a spheroid containing a LB (arrow). c.) Low power image of the central raphe nucleus (raphe) immunostained for α-synuclein shows neuronal immunoreactivity and scattered LNs. d.) The low power H&E stained section of the locus ceruleus (LC) shows a normal neuronal population. e.) The low power section of locus ceruleus (LC) immunostained for α-synuclein shows LBs and LNs. f.) Higher magnification of the locus ceruleus (LC) shows more clearly LBs (arrow) and LNs. g.) A low power H&E stained section of the substantia nigra (SN) shows a normal neuronal population. h.) A higher power H&E stained section shows LBs (arrow) in the substantia nigra (SN). i.) High power image of α-synuclein immunostained section of the hippocampus reveals sparse LNs in the CA2 sector. j.) A low power H&E stained section of the basal nucleus of Meynert (nbM) shows a normal neuronal population. k.) At higher magnification LNs are visible in the basal nucleus of Meynert (nbM) with α-synuclein immunohistochemistry. l.) Spare LBs and LNs are detected in the amygdala (Amyg) with α-synuclein immunohistochemistry. (c, d, e, g, j – 200x; a, b, f, h, I, k, l – 400x)