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

Boeve, Bradley F.; Dickson, Dennis W.; Olson, Eric J.; Shepard, John; Silber, MH; Ferman, Tanis J.; Ahlskog, J. Eric; Benarroch, Eduardo E.

doi:10.1016/j.sleep.2006.08.017

Cited by 163 publications

(117 citation statements)

References 13 publications

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“…Third, the evaluation of RBD symptom severity was made according to the criteria set in the revised edition of ICSD-1. More comprehensive rating scales for RBD severity that have been published more recently must be used to evaluate RBD symptoms (Boeve et al 2007;Stiasny-Kolster et al 2007;Li et al 2010). …”

Section: Discussionmentioning

confidence: 99%

Effectiveness of Pramipexole, a Dopamine Agonist, on Rapid Eye Movement Sleep Behavior Disorder

Sasai

Inoue

Matsuura

2012

Tohoku J. Exp. Med.

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Rapid eye movement (REM) sleep behavior disorder (RBD) is parasomnia characterized by REM sleep without atonia (RWA) and elaborate motor activity in association with dream mentation. Periodic leg movement during sleep (PLMS) is observed in a large share of patients with RBD, suggesting a common pathology: dopaminergic dysfunction. This study was undertaken to evaluate the effectiveness and mechanism of action of pramipexole, a dopamine agonist, on RBD symptoms. Fifteen patients (57-75 years old) with RBD with a PLMS index of more than 15 events/h shown by nocturnal polysomnography were enrolled. Sleep variables, the score of severity for RBD symptoms, REM density, and PLM index were compared before and after one month or more of consecutive pramipexole treatment. Correlation analysis was conducted between the rate of change in RBD symptoms and the rate of reduction of REM density. Fourteen patients with RBD (80.0%) achieved symptomatic improvement of RBD with pramipexole treatment, which reduced REM density and PLM index during non-REM sleep despite the unchanged amount of RWA. The rate of change in RBD symptoms correlated positively with the rate of REM density reduction. Significant reduction of the PLM index was observed in non-REM sleep but not in REM sleep. Periodic leg movement during sleep (PLMS) is often comorbid with RBD, suggesting a common pathogenesis of the two disorders. Its frequency in RBD is higher than that seen in the normal population, especially during the REM sleep period (Fantini et al. 2002). Although two previous case series investigated the effectiveness of pramipexole on RBD symptoms (Fantini et al. 2003;Schmidt et al. 2006), these studies did not respectively examine the effect of pramipexole on PLMS during non-REM (NREM) and REM sleep periods. Moreover, the pathophysiology of PLMS in idiopathic RBD remains unsolved.Episodes of violent behavior in RBD are mostly associated with nightmares. However, no report describes the effectiveness of pramipexole for alleviating nightmares in RBD or its relation to REM density, which possibly triggers dream imagery (Ogawa et al. 2005).To elucidate the mechanism of pramipexole action on the pathogenesis of RBD, we investigated its effects on RBD symptoms, with particular attention to REM-related parameters and PLMS in this pilot study. Methods Subjects

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Section: Discussionmentioning

confidence: 99%

Effectiveness of Pramipexole, a Dopamine Agonist, on Rapid Eye Movement Sleep Behavior Disorder

Sasai

Inoue

Matsuura

2012

Tohoku J. Exp. Med.

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“…We previously reported pathologic findings in iLBD, including decreased nigrostriatal dopaminergic innervation, that suggest that it may be presymptomatic PD rather than merely an incidental age-related change [6]. Boeve and coworkers reported on a patient with idiopathic RBD with brainstem Lewy bodies, but no significant neuronal loss in the substantia nigra, again consistent with iLBD [3]. Only a few studies have reported prodromal symptoms before presentation of overt clinical signs of MSA.…”

Section: Discussionmentioning

confidence: 77%

Glial cytoplasmic inclusions in neurologically normal elderly: prodromal multiple system atrophy?

et al. 2008

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In this study we used immunohistochemistry to screen for α-synuclein pathology in the brains of 241 individuals without clinical evidence of neurologic disease, and discovered 36 cases (15%) with incidental Lewy bodies (LBs) and one case, a 96-year-old woman (0.4%), with inclusions similar to those seen in multiple system atrophy (MSA), a nonfamilial neurodegenerative disorder characterized by parkinsonism, cerebellar ataxia and autonomic dysfunction and α-synuclein immunoreactive glial cytoplasmic inclusions (GCI). In a routine hospital autopsy series of 125 brains, we detected GCI in a neurologically normal 82-year-old man (0.8%). Both cases showed widespread GCI in the central nervous system, as well as a few neuronal cytoplasmic inclusions, but no neuronal loss or gliosis in vulnerable brain regions, including the substantia nigra, putamen, inferior olive and pontine base. Applying a recently proposed grading scale for MSA, the two cases showed pathology far below that detected in patients with clinically overt MSA, suggesting the possibility that these two individuals had preclinical MSA. The prevalence of clinically overt MSA is estimated to be about 4 per 100,000 persons (0.004%), which is far less than the frequency of GCI in this series (0.4%-0.8%). Further studies are needed to determine is GCI in neurologically normal elderly represents prodromal MSA or a rare non-progressive age-related α-synucleinopathy.

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“…Parenthetically, not all PD-related sleep disorders are linked to dopamine deficiency. Rapid eye movement sleep behavior disorder is a primary symptom of Lewy body disorders, 22 manifest as acting-out dreams. It may precede PD by many years 23 and is treated with a bedtime dose of a benzodiazepine (clonazepam).…”

Section: Levodopa Dyskinesias Are Often Benign and Treatablementioning

confidence: 99%

Cheaper, Simpler, and Better: Tips for Treating Seniors With Parkinson Disease

Ahlskog¹

2011

SciVee

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

Cited by 163 publications

References 13 publications

Effectiveness of Pramipexole, a Dopamine Agonist, on Rapid Eye Movement Sleep Behavior Disorder

Effectiveness of Pramipexole, a Dopamine Agonist, on Rapid Eye Movement Sleep Behavior Disorder

Glial cytoplasmic inclusions in neurologically normal elderly: prodromal multiple system atrophy?

Cheaper, Simpler, and Better: Tips for Treating Seniors With Parkinson Disease

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