Marcus M. Unger

A single-question screen for rapid eye movement sleep behavior disorder: A multicenter validation study†

Idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia that is an important risk factor for Parkinsons disease (PD) and Lewy body dementia. Its prevalence is unknown. One barrier to determining prevalence is that current screening tools are too long for large‐scale epidemiologic surveys. Therefore, we designed the REM Sleep Behavior Disorder Single‐Question Screen (RBD1Q), a screening question for dream enactment with a simple yes/no response.

Risk factors for neurodegeneration in idiopathic rapid eye movement sleep behavior disorder: A multicenter study

To assess whether risk factors for Parkinson disease and dementia with Lewy bodies increase rate of defined neurodegenerative disease in idiopathic rapid eye movement (REM) sleep behavior disorder (RBD).

Environmental risk factors for REM sleep behavior disorder: A multicenter case-control study

Objective: Idiopathic REM sleep behavior disorder is a parasomnia characterized by dream enactment and is commonly a prediagnostic sign of parkinsonism and dementia. Since risk factors have not been defined, we initiated a multicenter case-control study to assess environmental and lifestyle risk factors for REM sleep behavior disorder. Methods: Cases were patients with idiopathic REM sleep behavior disorder who were free of dementia and parkinsonism, recruited from 13 International REM Sleep Behavior Disorder Study Group centers. Controls were matched according to age and sex. Potential environmental and lifestyle risk factors were assessed via standardized questionnaire. Unconditional logistic regression adjusting for age, sex, and center was conducted to investigate the environmental factors. Results: A total of 694 participants (347 patients, 347 controls) were recruited. Among cases, mean age was 67.7 ± 9.6 years and 81.0% were male. Cases were more likely to smoke (ever smokers = 64.0% vs 55.5%, adjusted odds ratio [OR] = 1.43, p = 0.028). Caffeine and alcohol use were not different between cases and controls. Cases were more likely to report previous head injury (19.3% vs 12.7%, OR = 1.59, p = 0.037). Cases had fewer years of formal schooling (11.1 ± 4.4 years vs 12.7 ± 4.3, p < 0.001), and were more likely to report having worked as farmers (19.7% vs 12.5% OR = 1.67, p = 0.022) with borderline increase in welding (17.8% vs 12.1%, OR = 1.53, p = 0.063). Previous occupational pesticide exposure was more prevalent in cases than controls (11.8% vs 6.1%, OR = 2.16, p = 0.008). Conclusions: Smoking, head injury, pesticide exposure, and farming are potential risk factors for idiopathic REM sleep behavior disorder.

Restless Legs Syndrome (RLS) and Parkinson's disease (PD)—Related disorders or different entities?

The relationship between Restless Legs Syndrome (RLS) and Parkinsons disease (PD) is still controversial. Most genetic, pathological, and imaging data argue against a close association of these two disorders. Still, many studies reported an increased prevalence of RLS in PD patients. These studies are difficult to interpret because the current diagnostic criteria for RLS have not been validated in PD patients. Although many PD patients suffer from motor restlessness due to parkinsonism and may thus mimic RLS, the risk for (secondary) RLS in PD patients is probably slightly increased. This review provides an overview of the current pertinent literature and discusses the possible association between RLS and PD.

Assessment of idiopathic rapid-eye-movement sleep behavior disorder by transcranial sonography, olfactory function test, and FP-CIT-SPECT

Idiopathic rapid‐eye‐movement (REM) sleep behavior disorder (iRBD) has been suggested to be a risk factor for subsequent development of neurodegenerative disorders, especially Parkinsons disease (PD) and other α‐synucleinopathies. At present, it is not possible to predict whether or not an iRBD patient will eventually develop PD. Here, we report 5 iRBD patients who underwent a test battery comprising a neurological examination (including UPDRS rating), mini mental state examination testing, transcranial sonography, olfactory function testing, and presynaptic dopamine transporter imaging with FP‐CIT‐SPECT. Our preliminary data show the diverse pattern of individual combinations of pathological findings when a multimodal assessment approach is applied in this patient group. Large‐size longitudinal studies in iRBD patients are required to evaluate the usefulness of diagnostic tests to identify the subgroup of iRBD patients that is prone to develop PD.

Real-time Visualization of Altered Gastric Motility by Magnetic Resonance Imaging in Patients with Parkinson's Disease

Gastrointestinal motility is frequently affected in Parkinsons disease (PD) and has even been reported in early stages of PD. We hypothesized that gastric motility can be assessed in vivo by real‐time magnetic resonance imaging (MRI), an established, noninvasive method. After an overnight fast and a standardized test meal, 10 patients with PD (six drug naïve, four treated) and 10 healthy volunteers underwent real‐time MRI scanning of the stomach. Gastric motility was quantified by calculating the gastric motility indices (GMI) from transversal oblique und sagittal oblique MRI scans. There was a trend toward a decreased gastric motility in patients with PD compared with healthy controls (Mann‐Whitney test, P 0.059). This difference in peristalsis was due to a significant reduction in the amplitude of peristaltic contractions (P 0.029) and not to a decelerated velocity of the peristaltic waves (P 0.97). Real‐time MRI allows direct visualization of gastric motility in PD. In this pilot study, a relatively high interindividual variability impaired accurate separation of our PD sample from healthy controls. The trend toward decreased gastric motility is in accordance with previous studies that investigated gastric motility in patients with PD using other methods. Our study provides first demonstration of a possible underlying mechanism for disturbed gastric motility in PD (reduced amplitude of contractions versus altered velocity of peristaltic waves). Further studies in drug‐naïve PD patients are required to determine the discriminatory power and validity of this technique in PD.

DTI reveals hypothalamic and brainstem white matter lesions in patients with idiopathic narcolepsy

BACKGROUND Symptomatic narcolepsy is often related to hypothalamic, pontine, or mesencephalic lesions. Despite evidence of disturbances of the hypothalamic hypocretin system in patients with idiopathic narcolepsy, neuroimaging in patients with idiopathic narcolepsy revealed conflicting results and there is limited data on possible structural brain changes that might be associated with this disorder. METHODS We investigated with diffusion tensor imaging (DTI) whether microstructural abnormalities in the brain of eight patients with idiopathic narcolepsy with cataplexy are detectable compared to 12 healthy controls using a 1.5T MRI scanner. Whole-head DTI scans were analyzed without an a priori hypothesis. Voxelwise statistical analysis of fractional anisotropy (FA) data was performed using Tract-Based Spatial Statistics (TBSS), a non-linear analysis approach. RESULTS Patients with narcolepsy showed microstructural white matter changes in the right hypothalamus as well as in the left mesencephalon, pons, and medulla oblongata. Additionally, areas in the left temporal lobe, the pre- and postcentral gyrus, the frontal and parietal white matter, the corona radiata, the right internal capsule, and the caudate nucleus had altered microstructure in patients with narcolepsy. CONCLUSIONS Our study shows widespread microstructural white matter changes that are not visible on conventional MRI scans in patients with idiopathic narcolepsy. In support of the evidence from patients with symptomatic narcolepsy, we found microstructural changes in the hypothalamus, mesencephalon, pons, and medulla oblongata. Changes are in accordance with disturbances of the hypothalamic hypocretin system and its projections to mesencephalic and pontine areas regulating REM sleep.

Patients with idiopathic rapid‐eye‐movement sleep behavior disorder show normal gastric motility assessed by the 13C‐octanoate breath test

Delayed gastric emptying is a non‐motor symptom of Parkinsons disease. Few data exist on gastric emptying in early‐stage Parkinsons disease. In idiopathic rapid‐eye‐movement sleep behavior disorder, a presumable pre‐motor stage of Parkinsons disease, gastric emptying has not yet been investigated.

Nigrostriatal dysfunction in X-linked dystonia-parkinsonism (DYT3)

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Transcranial midbrain sonography in narcoleptic subjects with and without concomitant REM sleep behaviour disorder

Substantia nigra (SN) hyperechogenicity—a sonographic vulnerability marker for Parkinson’s disease (PD)—has been recently described in patients with idiopathic REM sleep behaviour disorder (RBD). It is not known whether subjects with narcolepsy (who frequently have associated RBD) also show SN hyperechogenicity. The aim of this study was to (1) evaluate SN echogenicity in narcolepsy and (2) determine whether transcranial sonography (TCS) differs in narcoleptic subjects with and without RBD. A total of 16 patients with narcolepsy–cataplexy (7 had a concomitant, video-polysomnographically based diagnosis of RBD) were examined with TCS by two investigators blinded to the clinical data. The size of the SN echogenic area in both subgroups was within the range previously described for healthy subjects. The brainstem raphe, however, was reduced in five of seven narcoleptic subjects with RBD, whereas only two of nine narcoleptic subjects without RBD exhibited this TCS finding. We conclude that evaluation of SN echogenicity does not discriminate between both subgroups. The absence of SN hyperechogenicity in narcoleptic patients with RBD supports the hypothesis that SN hyperechogenicity in patients with presumed idiopathic RBD is an additional risk marker for subsequent evolvement of PD rather than an RBD-immanent finding. Reduced echogenicity of the brainstem raphe might indicate an involvement of the serotonergic system in narcoleptic subjects with RBD.