Fragmentary myoclonus in idiopathic rapid eye movement sleep behaviour disorder.

Fragmentary myoclonus is a result of muscle activity consisting of brief potentials in surface electromyography during polysomnography. Excessive fragmentary myoclonus is defined by increased intensity of the potentials. A few studies report excessive fragmentary myoclonus occurrence in neurodegenerative diseases. Because idiopathic rapid eye movement sleep behaviour disorder is considered as an early stage of neurodegeneration with involvement of the brainstem, we charted the prevalence and quantified the intensity of excessive fragmentary myoclonus in idiopathic rapid eye movement sleep behaviour disorder. Twenty-nine patients (one woman, 28 men, mean age 68 years, SD 6.2) and 29 controls (two women, 27 men, mean age 65.6 years, SD 8.6) underwent polysomnography. Fragmentary myoclonus potentials were identified and counted according to internationally used criteria. Fragmentary myoclonus intensity was quantified by the fragmentary myoclonus index. Excessive fragmentary myoclonus was diagnosed in 75.9% (22 subjects) in idiopathic rapid eye movement sleep behaviour disorder, while in 34.5% (10 subjects) among the controls (p = 0.003). Quantitative analysis showed a wide-range fragmentary myoclonus index in idiopathic rapid eye movement sleep behaviour disorder (4.0-632.4; median 60.7) and in the controls (0.8-938.1; median 34.3). The overall difference in fragmentary myoclonus index was not significant between the groups; however, patients with idiopathic rapid eye movement sleep behaviour disorder showed trends for higher fragmentary myoclonus index scores in wakefulness (p = 0.027), N1 (p = 0.032), N3 (p = 0.046) and R (p = 0.007). Fragmentary myoclonus index does not correlate with age, idiopathic rapid eye movement sleep behaviour disorder duration or R stage atonia deficiency. The prevalence of excessive fragmentary myoclonus is higher in idiopathic rapid eye movement sleep behaviour disorder compared with the controls, so fragmentary myoclonus should be taken into account in future research of rapid eye movement sleep behaviour disorder and motor control in sleep.

Validation of the REM sleep behavior disorder screening questionnaire in the Czech population.

BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder (iRBD) affects 1-2% of people over 60 years of age and presents a high risk of developing a neurodegenerative disorder from the group of synucleinopathies, such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Therefore, screening tools are needed. In 2007, the rapid eye movement sleep behavior disorder screening questionnaire (RBD-SQ) was developed and has been translated into several languages. The aim of study was to assess the validity and reliability of the Czech version of the RBD-SQ in a mixed population of sleep clinic patients, supplemented by healthy volunteers and RBD patients. METHODS: Participants included 81 iRBD patients, 205 patients with other sleep disorders (obstructive sleep apnea, insomnia, restless legs syndrome and periodic limb movement disorder, other parasomnias, or central hypersomnias including narcolepsy) and 20 healthy volunteers. RESULTS: The mean RBD-SQ score in the iRBD patients was 9.4 ± 2.8 points, and in the non-RBD group it was 4.5 ± 3.0 (P < 0.0001). Receiver -operator analysis yielded an area under the curve of 0.864, suggesting good diagnostic performance of the scale. When using a cut-off value for positivity of 5 points, sensitivity was 0.89 and specificity was 0.62. CONCLUSIONS: The Czech version of the RBD-SQ is a sensitive tool for screening for iRBD patients and helps to identify subjects for complete clinical workup.

Smoking Prevalence and Its Clinical Correlations in Patients with Narcolepsy-cataplexy.

Narcolepsy-cataplexy (NC) is a chronic neurological disease with suggested autoimmune etiopathogenesis. Nicotine stimulates central nervous system and smoking increases the risk of autoimmune diseases. Assessment of smoking habits and its correlation to clinical parameters among 87 adult NC patients (38 male, 49 female) included night polysomnography and multiple sleep latency test. In our sample, 43.7% NC patients were regular smokers, and 19.5% former smokers compared to 22.2%, and 12.6%, respectively, in the general population. Patients started to smoke in the mean age of 20.0 (SD ±6.0) years. 72.2% of NC smokers started to smoke before the onset of NC and the mean of the delay between smoking onset and NC onset was 9.1 (±5.8) years. We found a direct correlation between smoking duration and the number of awakenings, duration of N1 sleep, REM sleep latency, and apnoea/hypopnoea index (AHI), and, on the contrary, indirect correlation between smoking duration and N3 sleep duration, showing that smoking duration consistently correlates with sleep macrostructure. Smoking is highly prevalent in NC and has relationship with clinical features of NC.

Comparison of quantitative REM without atonia parameters in isolated REM sleep behavior disorder and early untreated Parkinson's disease.

OBJECTIVES: To analyze REM sleep without atonia (RWA) metrics in patients with isolated REM sleep behavior disorder (iRBD), Parkinson's disease (PD) and healthy subjects and compare them in terms of degree of presumed brainstem damage. METHODS: Forty-nine iRBD patients, 62 PD patients and 38 healthy controls were included into the analysis. Detailed polysomnographic and clinical data including motor, olfactory, autonomic, and cognitive assessment were obtained in all participants and subsequently compared within groups without RBD (i.e., healthy controls, PD-RBD-) and with RBD (i.e., iRBD, PD-RBD+). SINBAR criteria were used to score RWA. RESULTS: Twenty-one PD patients (33.8 %) had RBD. When comparing PD-RBD-patients and controls, RWA tonic (p = 0.001) and RWA mixed (p = 0.03) were higher in PD-RBD-group. PD-RBD-patients had worse olfactory function than controls (p < 0.001); no significant difference in autonomic or cognitive function was registered. There were no significant differences in RWA parameters when comparing iRBD and PD-RBD + groups. iRBD patients had better olfactory function than PD-RBD+ (p = 0.006); no significant difference in autonomic or cognitive function was registered. PD-RBD + had worse autonomic (p = 0.006) and olfactory (p = 0.001) but not motor and cognitive function compared to PD-RBD-. CONCLUSIONS: Untreated de-novo PD patients without RBD have increased RWA metrics compared to healthy subjects indicating subclinical degeneration of brainstem nuclei responsible for RWA. iRBD patients do not differ in RWA metrics from untreated de-novo PD patients with premotor RBD suggesting a similar level of brainstem degeneration caudal to substantia nigra in both groups. Groups with RBD are associated with autonomic dysfunction.

Magnetic susceptibility changes in the brainstem reflect REM sleep without atonia severity in isolated REM sleep behavior disorder.

REM sleep without atonia (RWA) is the hallmark of isolated REM sleep behavior disorder (iRBD) and is caused by neurodegeneration of brainstem structures. Previously, quantitative susceptibility mapping (QSM) was shown to detect microstructural tissue changes in neurodegenerative diseases. The goal of the study was to compare brainstem magnetic susceptibility (MS) in iRBD and controls using the voxel-based QSM approach and to examine the association between brainstem MS and severity of RWA in iRBD. Sixty iRBD patients and 41 healthy controls were included in the study. Phasic, tonic, mixed RWA and SINBAR score was quantified. QSM maps were reconstructed with QSMbox software from a multi-gradient-echo sequence acquired at 3T MRI system and normalized using a custom T1 template. Voxel-based analysis with age and gender as covariates was performed using a two-sample t-test model for between-group comparison and using a linear regression model for association with the RWA parameters. Statistical maps were generated using threshold free cluster enhancement with p-value p < 0.05, corrected for family wise error. Compared to controls, the iRBD group had higher MS in bilateral substantia nigra (SN), red nucleus and the ventral tegmental area. MS positively correlated with iRBD duration in the right pedunculotegmental nucleus and white matter of caudal mesencephalic and pontine tegmentum and with phasic RWA in bilateral SN. QSM was able to detect MS abnormalities in several brainstem structures in iRBD. Association of MS levels in the brainstem with the intensity of RWA suggests that increased iron content in SN is related to RWA severity.

Characterization of memory profile in idiopathic REM sleep behavior disorder.

OBJECTIVE: The present study aims to examine whether declarative memory dysfunction relates to impaired core memory mechanisms or attentional and executive dysfunction in idiopathic REM Sleep Behavior Disorder (iRBD). METHOD: In this observational, cross-sectional study, were enrolled 82 individuals with the diagnosis of iRBD according to the International Classification of Sleep Disorders and 49-matched healthy controls fulfilling inclusion criteria. All participants underwent two memory tasks, namely the Rey Auditory Verbal Learning Test (RAVLT) and Memory Binding Test (MBT), which include conditions of varying degrees of dependence on executive functioning, as well as different indicators of core memory processes (e.g., learning, retention, relational binding). RESULTS: We used Bayesian multivariate generalized linear model analysis to evaluate the effect of iRBD on memory performance controlled for effects of age and sex. Individuals with iRBD displayed worse memory performance in the delayed free recall task (b = -0.37, 95% PPI [-0.69, -0.05]), but not on delayed recognition of the same material. Their performance in cued recall tasks both in immediate and delayed conditions was in comparison to controls relatively spared. Moreover, the deficit in delayed free recall was mediated by attention/processing speed. CONCLUSIONS: In iRBD, we replicated findings of reduced free recall based on inefficient retrieval (retrieval deficit), which was small in terms of effect size. Importantly, the memory profile across measures does not support the presence of core memory dysfunction, such as poor learning, retention or associative binding.

Trauma Immediately Preceding REM-Behavior Disorder: A Valuable Prognostic Marker?

Background: The definition of rapid eye movement (REM) sleep behavior disorder (RBD) has varied over the years. Rapid eye movement sleep behavior disorder can be considered isolated or idiopathic or can occur in the context of other disorders, including trauma-associated sleep disorder (TSD) and overlap parasomnia. However, whether trauma in RBD carries any prognostic specificity is currently unknown. Study Objectives: To test the hypothesis that RBD secondary to trauma is less likely to result in the development of neurodegeneration compared to idiopathic RBD (iRBD) without trauma in the general population. Methods: A retrospective cohort study of 122 consecutive RBD patients (103 males) at two tertiary sleep clinics in Europe between 2005 and 2020 was studied. Patients were diagnosed as having iRBD by video polysomnography (vPSG) and had a semi-structured interview at presentation, including specifically eliciting any history of trauma. Patients with secondary RBD to recognized causes were excluded from the study. Patients with iRBD were categorized into three groups according to reported trauma history: (1) No history of trauma, (2) traumatic experience at least 12 months prior to RBD symptom onset, and (3) traumatic experience within 12 months of RBD symptom onset. Idiopathic RBD duration was defined as the interval between estimated onset of RBD symptoms and last hospital visit or death. Follow-up duration was defined as the interval between iRBD diagnosis and last hospital visit or death. Results: In a follow-up period of up to 18 years, no patient who experienced trauma within 12 months preceding their iRBD diagnosis received a diagnosis of a neurodegenerative disorder (n = 35), whereas 38% of patients without trauma within the 12 months of symptom onset developed a neurodegenerative illness. These patients were also significantly more likely to have a family history of α-synucleinopathy or tauopathy. Conclusions: The development of RBD within 12 months of experiencing a traumatic life event, indistinguishable clinically from iRBD, did not lead to phenoconversion to a neurodegenerative disorder even after 18 years (mean follow up 6 years). We suggest that a sub-type of RBD be established and classified as secondary RBD due to trauma. Additionally, we advocate that a thorough psychological and trauma history be undertaken in all patients presenting with dream enactment behaviors (DEB).

Systematic video-analysis of motor events during REM sleep in idiopathic REM sleep behavior disorder, follow-up and DAT-SPECT.

Abnormal motor manifestations in REM sleep are the most visible feature of idiopathic REM sleep behavior disorder (iRBD), which precedes the overt alpha-synucleinopathy. The aim of this study was to perform a systematic visual analysis of the motor events (ME) captured during video-polysomnography, and clarify their relation to the disease severity. Thirty-four iRBD patients (5 women, 29 men; age 67.7 ± 7.2) with a mean follow-up duration 2.9 ± 1.1 years. and 33 controls (10 women, 23 men; age 61.5 ± 8.2) were examined. The ME captured during REM sleep were classified into four categories, previously defined by Frauscher et al. according to clinical severity: minor/simple jerks, major, complex and violent. An average frequency of 110.8 ± 75.2 ME per hour were identified in iRBD, 7.5 ± 11.6 in the controls (p < 0.001). Of these ME, 68.4% were classified as minor/simple jerks, 9.3% as major, 21.7% as complex and 0.7% as violent. The ME frequency was negatively associated with tracer binding on dopamine transporter single-photon emission computed tomography (DAT-SPECT); the association was stronger for caudate nucleus compared to putamen. During follow-up seven patients (24.1%) phenoconverted, yielding a yearly phenoconversion rate 8.3%. Violent ME were associated with increased hazard ratio for phenoconversion in frequency (p = 0.012) and total duration (p = 0.007). Patients with higher amounts of violent ME had a greater risk of phenoconversion; therefore, their role as a predictor should be considered. Additionally, ME were associated with nigrostriatal degeneration, according to DAT-SPECT. These findings indicate that the degree of the clinical severity of motor manifestations in iRBD reflects the severity of the disease.

Simultaneous tonic and phasic REM sleep without atonia best predicts early phenoconversion to neurodegenerative disease in idiopathic REM sleep behavior disorder.

STUDY OBJECTIVES: Rapid eye movement (REM) sleep without atonia (RWA) is the main polysomnographic feature of idiopathic REM sleep behavior disorder (iRBD) and is considered to be a promising biomarker predicting conversion to manifested synucleinopathy. Besides conventionally evaluated tonic, phasic and any RWA, we took into consideration also periods, when phasic and tonic RWA appeared simultaneously and we called this activity "mixed RWA." The study aimed to evaluate different types of RWA, to reveal the most relevant biomarker to the conversion. METHODS: A total of 55 patients with confirmed iRBD were recruited with mean follow-up duration 2.3 ± 0.7 years. Scoring of RWA was based on Sleep Innsbruck Barcelona rules. Positive phenocoversion was ascertained according to standard diagnostic criteria during follow-up. Receiver operator characteristic analysis was applied to evaluate predictive performance of different RWA types. RESULTS: A total of nine patients (16%) developed neurodegenerative diseases. Yearly phenoconversion rate was 5.5%. Significantly higher amounts of mixed (p = 0.009), tonic (p = 0.020), and any RWA (p = 0.049) were found in converters. Optimal cutoffs differentiating the prediction were 16.4% (sensitivity 88.9; specificity 69.6) for tonic, 4.4% (sensitivity 88.9; specificity 60.9) for mixed, and 36.8% (sensitivity 77.8; specificity 65.2) for any RWA. With area under the curve (AUC) 0.778, mixed RWA has proven to be the best predictive test followed by tonic (AUC 0.749) and any (AUC 0.710). CONCLUSIONS: Mixed, tonic and any RWA may serve as biomarkers predicting the conversion into neurodegenerative disease in iRBD. The best predictive value lies within mixed RWA, thus it should be considered as standard biomarker.

Relations of non-motor symptoms and dopamine transporter binding in REM sleep behavior disorder.

The aim of this study was to evaluate associations of motor and non-motor symptoms with dopamine transporter binding in prodromal stage of synucleinopathies. We examined 74 patients with idiopathic REM sleep behavior disorder (RBD), which is a prodromal synucleinopathy, and 39 controls using Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment, University of Pennsylvania Smell Identification Test (UPSIT), Farnsworth-Munsell 100 hue test, orthostatic test, Scales for Outcomes in PD-Autonomic, Beck depression inventory-II, State-Trait Anxiety Inventory, and video-polysomnography. Electromyographic muscle activity during REM sleep was quantified according to Sleep Innsbruck-Barcelona criteria. In 65 patients, dopamine transporter single-photon emission computed tomography (DAT-SPECT) imaging was performed, putaminal binding ratio was calculated and scans were classified as normal, borderline, or abnormal. Compared to controls, RBD patients had significantly more severe scores in all examined tests. Patients with abnormal DAT-SPECT had higher MDS-UPDRS motor score (p = 0.006) and higher prevalence of orthostatic hypotension (p = 0.008). Putaminal binding ratio was positively associated with UPSIT score (p = 0.03) and negatively associated with tonic (p = 0.003) and phasic (p = 0.01) muscle activity during REM sleep. These associations likely reflect simultaneous advancement of underlying pathology in substantia nigra and susceptible brainstem and olfactory nuclei in prodromal synucleinopathy.

Prospective memory impairment in idiopathic REM sleep behavior disorder.

OBJECTIVE: The aim of the present study was to investigate if prospective memory (PM) is impaired in idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). RBD is a parasomnia characterized by dream enactment and by REM sleep without muscle atonia. iRBD is considered as the initial stage of neurodegeneration with pathological storage of alpha-synuclein. METHOD: Sixty iRBD patients with polysomnography-confirmed RBD without parkinsonism and dementia and 30 demographically matched normal controls (NC) were enrolled in the present study. Clinical assessment included Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), dopamine transporter single-photon emission computed tomography (DaT-SPECT) for imaging synapses of dopaminergic neurons in the striatum and a neuropsychological battery with embedded time-based and event-based PM measures. RESULTS: iRBD differed significantly from NC in event-based PM, a number of event-based failures to recall intention and total PM performance (all p < .001) but did not differ in time-based PM and recognition. PM did not contribute to impairment of instrumental activities of daily living in iRBD. Despite being preserved in iRBD in comparison to NC, time-based PM correlated significantly with dopaminergic neuronal loss measured by DaT-SPECT. CONCLUSIONS: We show evidence for a differential pattern of PM impairment in iRBD with severe impairment of event-based and concurrent preservation of time-based PM. We theorize that event-based PM impairment in iRBD is caused by severe impairment of retention and recognition mechanisms in episodic memory whereas time-based PM seems to be affected by reduced striatal dopaminergic synapses.