Polysomnographic Predictors of Sleep, Motor, and Cognitive Dysfunction Progression in Parkinson's Disease.

PURPOSE OF REVIEW: Sleep disturbances are an important nonmotor feature of Parkinson's disease (PD) that can cause polysomnographic (PSG) alterations. These alterations are already present in early PD and may be associated with a specific disease course. This systematic review describes the role of PSG variables as predictors of sleep dysfunction, motor and cognitive dysfunction progression in PD. RECENT FINDINGS: Nineteen longitudinal cohort studies were included. Their main findings were that (1) REM sleep behavioral events, REM sleep without atonia (RSWA), and electroencephalography (EEG) changes (mainly microsleep instability) are predictors of the development of REM sleep behavior disorder (RBD); (2) RBD, RSWA, and lower slow-wave sleep energy predict motor progression; (3) RBD, EEG slowing, and sleep spindles changes are predictors of cognitive deterioration; and (4) OSA is associated with severe motor and cognitive symptoms at baseline, with inconsistent findings on the effect of continuous positive airway pressure (CPAP) therapy for these symptoms. The results of our systematic review support a role of the video-PSG in disease progression prediction in PD and its usefulness as a biomarker. However, future studies are needed to investigate whether treatment of these PSG abnormalities and sleep disturbances may have a neuroprotective effect on disease progression.

Dissociative symptoms and sleep parameters--an all-night polysomnography study in patients with insomnia.

BACKGROUND: Dissociative disorders encompass a range of symptoms varying from severe absent-mindedness and memory problems to confusion about one's own identity. Recent studies suggest that these symptoms may be the by-products of a labile sleep-wake cycle. METHODS: In the current study, we explored this issue in patients suffering from insomnia (N=46). We investigated whether these patients have raised levels of dissociative symptoms and whether these are related to objective sleep parameters. Patients stayed for at least one night in a specialized sleep clinic, while sleep EEG data were obtained. In addition, they completed self-report measures on dissociative symptoms, psychological problems, and sleep characteristics. RESULTS: Dissociative symptom levels were elevated in patients suffering from insomnia, and were correlated with unusual sleep experiences and poor sleep quality. Longer REM sleep periods and less time spent awake during the night were predictive of dissociation. CONCLUSIONS: This is the first study to show that insomnia patients have raised dissociative symptom levels and that their dissociative symptoms are related to objective EEG parameters. These findings are important because they may inspire sleep-related treatment methods for dissociative disorders.

Prevalence of Insomnia and Sleep Habits during the First and Second Wave of COVID-19 in Belgium.

Belgium has one of the highest numbers of COVID-19 cases per 1 million inhabitants. The pandemic has led to significant societal changes with repercussions on sleep and on mental health. We aimed to investigate the effect of the first and the second wave of COVID-19 on the sleep of the Belgian populationWe launched two online questionnaires, one during the first lockdown (7240 respondents) and one during the second (3240 respondents), to test differences in self-reported clinical insomnia (as measured by the Insomnia Severity Index) and sleep habits during the two lockdowns in comparison with the pre-COVID period. The number of persons with clinical insomnia rose during the first lockdown (19.22%) and further during the second (28.91%) in comparison with pre-lockdown (7.04-7.66%). Bed and rise times were delayed and there was an increased time in bed and sleep onset latency. There was further a decrease in total sleep time and in sleep efficiency during both confinements. The prevalence of clinical insomnia quadrupled during the second wave in comparison with the pre-lockdown situation. Sleep habits were most altered in the younger population, indicating a greater risk for this group to develop a sleep-wake rhythm disorder.

Impaired bed mobility in prediagnostic and de novo Parkinson's disease.

BACKGROUND: Wearable technology research suggests that nocturnal movements are disturbed in early Parkinson's disease (PD). In this study, we investigate if patients also already experience impaired bed mobility before PD diagnosis. Furthermore, we explore its association with motor and nonmotor features and its value for phenoconversion and disease progression prediction. METHODS: PPMI data were downloaded for de novo PD subjects, subjects at-risk for developing a synucleinopathy (with isolated REM sleep behavior disorder, hyposmia or a pathogenic genetic variant) and controls. Impaired bed mobility was assessed with the MDS-UPDRS part 2 item 9. A frequency analysis was performed. Multivariable logistic regression analyses were used to investigate the association with other PD variables. Cox proportional-hazards models were used to test if difficulties with turning in bed could predict phenoconversion. Linear mixed models were used to evaluate if difficulties with turning in bed could predict disease progression. RESULTS: Of the at-risk subjects, 9.2-12.5% experienced difficulties with turning in bed vs. 25.0% of de novo PD subjects and 2.5% of controls. Impaired turning ability was associated with MDS-UPDRS motorscore (axial signs in the at-risk group, bradykinesia in the de novo PD group) and SCOPA-AUT score (gastrointestinal symptoms). In addition, difficulties with turning in bed were a significant predictor for phenoconversion in the at-risk group and for development of motor complications in the de novo PD group. CONCLUSION: Our findings suggest that difficulties with turning in bed can be helpful as clinical symptom for a prodromal PD screening and for motor complication prediction in early PD.

REM sleep without atonia and nocturnal body position in prediagnostic Parkinson's disease.

BACKGROUND: Sleep disturbances are features of Parkinson's disease (PD), that can already occur before PD diagnosis. The most investigated prodromal PD sleep disorder is REM sleep behavior disorder (RBD). The relation between other polysomnographic (PSG) alterations and the prediagnostic stages of PD, however, is less clear. METHODS: We performed a retrospective case-control study to characterize polysomnographic alterations in PD and prediagnostic PD. We included 63 PD subjects (33 subjects that underwent a video-PSG before PD diagnosis [13 with and 20 without RBD] and 30 subjects that underwent a PSG after PD diagnosis) and 30 controls. PSGs were analyzed for sleep stages, different RSWA variables, body position, arousals, periodic limb movements, and REM density. RESULTS: Higher subscores of all RSWA variables were observed in subjects with PD and prediagnostic PD (with and without RBD). Total RSWA, tonic RSWA and chin RSWA severity were significant predictors for all PD and prediagnostic PD groups. Our study also shows a higher percentage of nocturnal supine body position in all PD and prediagnostic PD groups. Supine body position percentage is the highest in the PD group and has a positive correlation with time since diagnosis. CONCLUSIONS: These findings suggest that increased total, tonic and chin RSWA as well as nocturnal supine body position are already present in prediagnostic PD, independently of RBD status. Prospective longitudinal studies are necessary to confirm the additional value of these PSG abnormalities as prodromal PD biomarkers.

Caspr2 autoantibody-associated Morvan syndrome predating thymoma relapse by 30 months.

Morvan's syndrome (MoS) is a rare autoimmune disorder characterized by central nervous system involvement, autonomic dysfunction and peripheral nerve hyperexcitability. MoS is believed to be caused by autoantibodies targeting contactin-associated protein 2 (Caspr2), a subunit of the neuronal voltage-gated potassium channel (VGKC) complex, usually in association with thymoma, less commonly with other malignancies. This case highlights an exceptional case of severe sleep disturbances and behavioural changes due to MoS, in a patient who would present with and be treated successfully for a second relapse of thymoma 30 months later. Originally he suffered from ocular myasthenia, another autoimmune disorder, which led to diagnosis of his original thymoma and first relapse.

Polysomnographic phenotype of isolated REM sleep without atonia.

OBJECTIVE: Isolated REM sleep without atonia (iRSWA) is regarded as a prodromal phase of REM sleep behavior disorder and synucleinopathies. In iRSWA patients, we investigated the polysomnographic characteristics that are known to be altered in (prodromal) Parkinson's disease (PD): periodic limb movements of sleep [PLMS] (increased), REM density (reduced), and heart rate variability ([HRV] (reduced). METHODS: We compared video-polysomnographic studies of 49 iRSWA subjects with 41 controls. RSWA and PLMS were scored visually. REM density (REM/hour) and HRV were calculated automatically. RESULTS: We found a higher median total (15.90 vs 7.20; p = 0.001), REM (21.80 vs 11.0; p < 0.001) and non-REM (11.75 vs 5.72; p = 0.027) PLMS index, and a higher mean REM density (342.45 vs 275.96; p = 0.010) in the iRSWA group, with a significant positive correlation between RSWA severity and these variables (r = 0.39; p < 0.00, r = 0.48; p < 0.001, r = 0.24; p = 0.021, r = 0.28; p = 0.012). We found no significant difference in HRV between groups. CONCLUSIONS: Our results suggest an association between RWSA and REM density and PLMS, but not HRV. The positive correlation between these variabilities may imply overlapping pathophysiological processes. SIGNIFICANCE: The evidence of higher REM density and normal HRV weakens the hypothesis that iRWSA is a prodromal PD stage. An alternative interpretation is, however, that REM density and HRV change during caudal-rostral neurodegeneration.

Frequency and characteristic features of REM sleep without atonia.

OBJECTIVES: Isolated REM sleep without atonia (iRSWA) is regarded as prodromal phase of REM sleep behavior disorder (RBD) and synucleinopathies. Other factors, however, have also been described to cause RSWA, including sleep apnea, antidepressants use and narcolepsy. We investigated the frequency of RSWA and its different etiologies. METHODS: We investigated RSWA in patients that underwent a clinical video polysomnography. In iRSWA subjects, we examined polysomnography indication and two markers of prodromal Parkinson's disease: excessive daytime sleepiness and depressive symptoms, with a case-control design. RESULTS: Of the 864 included polysomnographies, 188 were positive for RSWA (21.8%), 17 for RBD (2.0%) and 48 for iRSWA (5.6%). Mean Epworth Sleepiness Scale scores were 9.8 ±â€¯4.8 (iRSWA subjects) and 7.5 ±â€¯4.9 (controls), p = 0.014. Mean Beck Depression Inventory-II scores were 11.3 ±â€¯7.9 (iRSWA subjects) and 9.5 ±â€¯8.4 (controls), p = 0.229. Excessive daytime sleepiness was more often the polysomnography indication in the iRSWA group (p = 0.006). CONCLUSIONS: RSWA is a frequent finding in the context of antidepressant use or synucleinopathies. iRSWA subjects reported increased excessive daytime sleepiness and more often had excessive daytime sleepiness as polysomnography indication. SIGNIFICANCE: Our study provides evidence for high frequency of RSWA, underscoring the need for longitudinal studies in iRSWA patients, with interest for conversion to synucleinopathies.

REM sleep without atonia and the relation with Lewy body disease.

REM sleep without atonia (RSWA) is the polysomnographic finding of persistent muscle tone during REM sleep, resulting in paroxysmal phasic or tonic EMG activity. RSWA is essential for the diagnosis of REM sleep behavior disorder (RBD), but can also occur without dream-enacting behavior. Loss of atonia during REM sleep is considered as a biomarker for synucleinopathies. We will give an overview of the pathophysiology of RSWA and will highlight the diagnostic methods for RSWA. We will describe the different etiologies of RSWA and finally we will focus on the role of RSWA as biomarker for Lewy body disease. RSWA severity in isolated RBD patients is a potential predictor for early conversion to Parkinson's disease (PD) or dementia with Lewy bodies. In PD patients, RSWA severity is associated with more severe motor symptoms and disease progression. Future studies are needed to delineate the importance of isolated RSWA as prodromal marker of Lewy body disease.

IgLON5-Associated Encephalitis With Atypical Brain Magnetic Resonance Imaging and Cerebrospinal Fluid Changes.

IgLON5-associated encephalitis is a syndrome with different clinical presentations consisting of sleep dysfunction, bulbar dysfunction, chorea, and progressive supranuclear palsy-like symptoms whereas dysautonomy and cognitive decline usually appear in later stages of the disease. We report a case of a patient with IgLON5-associated encephalitis presenting with rapidly progressive cognitive decline and atypical inflammatory lesions on brain magnetic resonance imaging, oligoclonal bands on cerebrospinal fluid, anti-IgLON5 antibodies exclusively of the IgG1 class, and a fierce inflammatory reaction on brain biopsy, who responded favorably to immunotherapy.

Evaluation of a Trial Period With a Sleep Position Trainer in Patients With Positional Sleep Apnea.

STUDY OBJECTIVES: To assess the overall clinical effectiveness of a sleep position trainer (SPT) in patients with positional obstructive sleep apnea (POSA) and to evaluate how many patients were willing to continue treatment after a 1-month trial period. METHODS: Patients in whom POSA was diagnosed underwent a 1-month trial period with the SPT. Home sleep apnea tests were used to measure baseline data and data following the trial period with the SPT. RESULTS: The 79 patients who completed the study protocol were 81% male, had a mean age of 52 ± 12 years, and a median baseline respiratory event index (REI) of 11 (8, 16) events/h. A significant reduction in overall REI to 5 (3, 10) events/h was observed with the SPT as compared to baseline (P < .001). The median percentage of sleep time in the supine position decreased significantly from 27 (20, 48) to 7 (2, 20) with the SPT (P < .001). Adherence was found to be 95 ± 8%. Of the 44 patients who decided to continue treatment, 27 were categorized as responders (having a decrease in REI of at least 50%) and 17 were non-responders. The most important reasons for not purchasing the SPT were poor objective results, intolerance to the vibrations, cost of the device, persistent daytime sleepiness, or patient preference for other treatment options. CONCLUSIONS: Treatment with the SPT came with high adherence rates and was effective in reducing REI and supine sleep position. The trial period is in the patients' best interest, as it may prevent those who will not benefit from positional training from purchasing an SPT.