Rapid eye movement behavior disorder

Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study.

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Background

We postulated that idiopathic rapid-eye-movement (REM) sleep behaviour disorder (IRBD) represents the prodromal phase of a Lewy body disorder and that, with sufficient follow-up, most cases would eventually be diagnosed with a clinical defined Lewy body disorder, such as Parkinson’s disease (PD) or dementia with Lewy bodies (DLB).

Methods

Patients from an IRBD cohort recruited between 1991 and 2003, and previously assessed in 2005, were followed up during an additional period of 7 years. In this original cohort, we sought to identify the nature and frequency of emerging defined neurodegenerative syndromes diagnosed by standard clinical criteria. We estimated rates of survival free from defined neurodegenerative disease by means of the Kaplan-Meier method. We further characterised individuals who remained diagnosed as having only IRBD, through dopamine transporter (DAT) imaging, transcranial sonography (TCS), and olfactory testing. We did a neuropathological assessment in three patients who died during follow-up and who had the antemortem diagnosis of PD or DLB.

Findings

Of the 44 participants from the original cohort, 36 (82%) had developed a defined neurodegenerative syndrome by the 2012 assessment (16 patients were diagnosed with PD, 14 with DLB, one with multiple system atrophy, and five with mild cognitive impairment). The rates of neurological-disease-free survival from time of IRBD diagnosis were 65·2% (95% CI 50·9 to 79·5) at 5 years, 26·6% (12·7 to 40·5) at 10 years, and 7·5% (−1·9 to 16·9) at 14 years. Of the four remaining neurological-disease-free individuals who underwent neuroimaging and olfactory tests, all four had decreased striatal DAT uptake, one had substantia nigra hyperechogenicity on TCS, and two had impaired olfaction. In three patients, the antemortem diagnoses of PD and DLB were confirmed by neuropathological examination showing widespread Lewy bodies in the brain, and α-synuclein aggregates in the peripheral autonomic nervous system in one case. In these three patients, neuronal loss and Lewy pathology (α-synuclein-containing Lewy bodies and Lewy neurites) were found in the brainstem nuclei that regulate REM sleep atonia.

Interpretation

Most IRBD individuals from our cohort developed a Lewy body disorder with time. Patients who remained disease-free at follow-up showed markers of increased short-term risk for developing PD and DLB in IRBD, such as decreased striatal DAT binding. Our findings indicate that in most patients diagnosed with IRBD this parasomnia represents the prodromal phase of a Lewy body disorder. IRBD is a candidate for the study of early events and progression of this prodromal phase, and to test disease-modifying strategies to slow or stop the neurodegenerative process.

Source: Lancet

More Evidence Links REM Sleep Behavior Disorder and Neurodegenerative Disease.

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Most patients diagnosed with idiopathic REM sleep behavior disorder advance to a neurodegnerative disease associated with alpha synuclein deposition (Lewy body disease) within a decade.

Several longitudinal studies have demonstrated a consistent association between idiopathic rapid eye movement (REM) sleep behavior disorder (IRBD) and the development of neurodegenerative disorders associated with alphasynucleinopathy, including Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple systems atrophy (MSA). In one previously described cohort of 44 patients with symptomatic IRBD for a median interval of 11 years and followed clinically for a median of 4.5 years, 45% met criteria for a neurodegenerative disorder. Now, the investigators report their findings in this cohort after an additional 7-year interval.

The conversion to a defined neurodegenerative diagnosis was 82% (16 PD, 14 DLB, 1 MSA, and 5 mild cognitive impairment). Four cohort members were lost to follow-up. Three patients in the cohort underwent autopsy during the period of study, which demonstrated characteristic pathological changes confirming diagnoses of PD in 2 and DLB in 1. Compared with healthy controls without IRBD, 4 patients who did not meet criteria for a neurodegenerative disorder demonstrated decreased striatal uptake of dopamine transporter, a biomarker associated with alphasynucleinopathies.

Comment: Although the sample size is relatively small, this report emphasizes the importance of longitudinal observations in slowly progressive neurodegenerative disorders. The findings highlight an opportunity to identify at-risk individuals and potentially intervene as disease-modifying therapies become available. However, clinicians should look carefully for other causes of dream-enactment behavior, such as medications or concomitant sleep disorders. In the absence of such factors, clinicians should confirm the diagnosis with polysomnography. As the authors suggest, idiopathic RBD may be more accurately termedisolated RBD. Patients who have REM sleep behavior disorder but are asymptomatic for parkinsonism or dementia should be made aware of the risk and the need for continued clinical follow-up.

 

Source:Journal Watch Neurology