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1.
Sleep Med Clin ; 14(3): 351-362, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31375203

RESUMO

In recent years, the diagnostic approach to rapid eye movement (REM) sleep behavior disorder (RBD) has become more objective and accurate. This was achieved mainly by introduction of methods to exactly quantify electromyographic (EMG) activity in various muscles during REM sleep. The most established muscle combination for RBD diagnosis is the mentalis and upper extremity EMG. Computer-assisted systems for this analysis have been described, and an increasing number of studies looked into analysis of video events. Recently, prodromal phases of isolated RBD have been recognized.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31454761

RESUMO

OBJECTIVES: We investigated the associations with HLA and microtubule-associated protein tau (MAPT) H1 haplotype in anti-IgLON5 disease, a recently identified disorder characterized by gait instability, brainstem dysfunction, and a prominent sleep disorder in association with IgLON5 antibodies and pathologic findings of a novel neuronal-specific tauopathy. METHODS: We compared the HLA alleles and MAPT H1/H1 genotype of 35 patients with anti-IgLON5 with healthy controls. The on-line server tool NetMHCIIpan 3.1 was used to predict the IgLON5 peptide binding to HLA Class II molecules. RESULTS: The HLA-DRB1*10:01-DQB1*05:01 haplotype was overrepresented in patients with anti-IgLON5 disease (OR = 54.5; 95% CI: 22.2-133.9, p < 0.0001). In addition, HLA-DQA was genotyped in 27 patients, and 25 (92.6%) of them had DQ molecules composed by DQA1*01 and DQB1*05 chains compared with 148/542 (27.3%) controls (OR = 43.9; 95% CI: 10.4-185.5, p < 0.0001). Patients DRB1*10:01 positive developed more frequently sleep or bulbar symptoms than those carrying other HLA alleles (70.0% vs 26.7%; p = 0.011). Prediction algorithms identified 2 IgLON5 peptides (1 located in the signal sequence) that showed strong binding to HLA-DRB1*10:01 and other HLA-DRB1, but not to HLA-DQA and HLA-DQB molecules. The MAPT H1/H1 homozygous genotype was present in 20/24 (83.3%) anti-IgLON5 Caucasian patients compared with 54/116 (46.5%) healthy controls (p = 0.0007). CONCLUSIONS: The robust association of anti-IgLON5 disease with distinct HLA Class II molecules supports a primary autoimmune origin. The significant association of MAPT H1 haplotype also suggests that an underlying neurodegenerative process could be involved in anti-IgLON5 disease.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31302665

RESUMO

Neurological autoimmune diseases are characterized by an inappropriate immune response that by mistake targets the nervous system. As a result, patients experiment a number of neurological manifestations that may include insomnia, excessive daytime sleepiness, cataplexy, central hypoventilation, and REM sleep behavior disorder. Polysomnographic evaluation may reveal disorganized sleep architecture involving both NREM and REM sleep, and REM sleep intrusions into wakefulness. The study of sleep disorders in the setting of autoimmune diseases (e.g., narcolepsy, anti-IgLON5 disease, paraneoplastic neurological syndromes) shows that an abnormal immune-mediated (humoral or cellular) response target the neuronal structures (e.g., brainstem, hypothalamus) and neurotransmitters systems (e.g., hypocretin) that regulate sleep resulting in sleep impairment. It is a window to examine the link between the autoimmune system and the sleep regulation at the molecular, cellular, and anatomic level.

4.
Mov Disord ; 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31361367

RESUMO

BACKGROUND: Aggregation of α-synuclein is central to the pathophysiology of PD. Biomarkers related to α-synuclein may be informative for PD diagnosis/progression. OBJECTIVES: To analyze α-synuclein in CSF in drug-naïve PD, healthy controls, and prodromal PD in the Parkinson's Progression Markers Initiative. METHODS: Over up to 36-month follow-up, CSF total α-synuclein and its association with MDS-UPDRS motor scores, cognitive assessments, and dopamine transporter imaging were assessed. RESULTS: The inception cohort included PD (n = 376; age [mean {standard deviation} years]: 61.7 [9.62]), healthy controls (n = 173; age, 60.9 [11.3]), hyposmics (n = 16; age, 68.3 [6.15]), and idiopathic rapid eye movement sleep behavior disorder (n = 32; age, 69.3 [4.83]). Baseline CSF α-synuclein was lower in manifest and prodromal PD versus healthy controls. Longitudinal α-synuclein decreased significantly in PD at 24 and 36 months, did not change in prodromal PD over 12 months, and trended toward an increase in healthy controls. The decrease in PD was not shown when CSF samples with high hemoglobin concentration were removed from the analysis. CSF α-synuclein changes did not correlate with longitudinal MDS-UPDRS motor scores or dopamine transporter scan. CONCLUSIONS: CSF α-synuclein decreases early in the disease, preceding motor PD. CSF α-synuclein does not correlate with progression and therefore does not reflect ongoing dopaminergic neurodegeneration. Decreased CSF α-synuclein may be an indirect index of changes in the balance between α-synuclein secretion, solubility, or aggregation in the brain, reflecting its overall turnover. Additional biomarkers more directly related to α-synuclein pathophysiology and disease progression and other markers to be identified by, for example, proteomics and metabolomics are needed. © 2019 International Parkinson and Movement Disorder Society.

5.
Sleep ; 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31323084

RESUMO

OBJECTIVE: To evaluate the role of sleep cyclic alternating pattern (CAP) in patients with isolated REM sleep behavior disorder (IRBD) and ascertain whether CAP metrics might represent a marker of phenoconversion to a defined neurodegenerative condition. METHODS: Sixty-seven IRBD patients were included and classified into patients who phenoconverted to a neurodegenerative disease (RBD converters: converter REM sleep behavior disorder [cRBD]; n = 34) and remained disease-free (RBD non-converters: non-converter REM sleep behavior disorder [ncRBD]; n = 33) having a similar follow-up duration. Fourteen age- and gender-balanced healthy controls were included for comparisons. RESULTS: Compared to controls, CAP rate and CAP index were significantly decreased in IRBD mainly due to a decrease of A1 phase subtypes (A1 index) despite an increase in duration of both CAP A and B phases. The cRBD group had significantly lower values of CAP rate and CAP index when compared with the ncRBD group and controls. A1 index was significantly reduced in both ncRBD and cRBD groups compared to controls. When compared to the ncRBD group, A3 index was significantly decreased in the cRBD group. The Kaplan-Meier curve applied to cRBD estimated that a value of CAP rate below 32.9% was related to an average risk of conversion of 9.2 years after baseline polysomnography. CONCLUSION: IRBD is not exclusively a rapid eye movement (REM) sleep parasomnia, as non-rapid eye movement (non-REM) sleep microstructure can also be affected by CAP changes. Further studies are necessary to confirm that a reduction of specific CAP metrics is a marker of neurodegeneration in IRBD.

6.
Sleep ; 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31198936

RESUMO

STUDY OBJECTIVE: To characterize the sleep disorder of anti-IgLON5 disease. METHODS: We reviewed 27 video-polysomnographies (V-PSG), 6 multiple sleep latency tests (MSLT), 2 videsomnoscopies with dexmedetomidine, and 10 actigraphies recorded during the disease course of five patients. Due to severe sleep architecture abnormalities, we used a novel modified sleep scoring system combining conventional stages with a descriptive approach in which two additional stages were identified: undifferentiated-NREM (UN-NREM) and poorly structured N2 (P-SN2) sleep that were characterized by abnormal motor activation and absence or sparse elements of conventional NREM sleep. RESULTS: Sleep-related vocalizations, movements, behaviors, and respiratory abnormalities were reported by bed-partners. In all patients, NREM sleep onset and sleep reentering after an awakening occurred as UN-NREM (median: 29.8% of total sleep time [TST]) and P-SN2 sleep (14.5% TST) associated with vocalizations and simple and quasi-purposeful movements. Sleep initiation was normalized in one patient with a high dose of steroids, but NREM sleep abnormalities reappeared in subsequent V-PSG. In all patients, if sleep continued uninterrupted, there was a progressive normalization with normal N2 (11.7% TST) and N3 (22.3% TST) sleep but stridor and obstructive apnea emerged. REM sleep behavior disorder (RBD) occurred in four patients. Sleep initiation was also altered in MSLT and dexmedetomidine-induced sleep. Actigraphy showed a 10-fold increase of nocturnal activity compared with controls. Sleep abnormalities remained stable during the disease. CONCLUSIONS: The sleep disorder of anti-IgLON5 disease presents as a complex sleep pattern characterized by abnormal sleep initiation with undifferentiated NREM sleep, RBD, periods of normal NREM sleep, stridor, and obstructive apnea.

8.
Sleep ; 42(7)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-30946468

RESUMO

OBJECTIVE: The main objective of this study was to study rapid eye movement (REM) sleep behavior disorder (RBD) and other sleep disorders in dementia with Lewy bodies (DLB). METHODS: Consecutive patients with DLB and mild dementia severity were recruited irrespective of sleep complaints. Patients underwent clinical interview, assessment of sleep scales, and video-polysomnography (V-PSG). RBD was diagnosed with V-PSG based on electromyographic and audiovisual analysis. RESULTS: Thirty-five patients (65.7% men; mean age 77.7 ± 6.1 years) were evaluated. Poor sleep quality (54.3%), hypersomnia (37.1%), snoring (60%), and abnormal nocturnal behaviors (77.1%) were reported. Sleep-wake architecture abnormalities occurred in 75% patients and consisted of occipital slowing on awake electroencephalography (EEG; 34.4%), the absence of sleep spindles and K complexes (12.9%), slow frequency sleep spindles (12.9%), delta activity in REM sleep (19.2%), and REM sleep without atonia (44%). Three patients showed hallucinatory-like behaviors and 10 patients showed abnormal behaviors during arousals mimicking RBD. RBD was diagnosed in 50% of those patients in whom sufficient REM sleep was attained. Of these, 72.7% were not aware of displaying dream-enacting behaviors and in 63.7% RBD preceded the onset of cognitive impairment. For RBD diagnosis, the sensitivity of Mayo Sleep Questionnaire was 50%, specificity was 66.7%, positive predictive value was 83.3%, and negative predictive value was 28%. False-positive RBD cases according to clinical history had hallucinatory-like behaviors, severe obstructive sleep apnea, and prominent periodic limb movements in sleep. Occipital EEG frequency while awake and rate of electromyographic activity in REM sleep were negatively correlated, suggesting a common subcortical origin. CONCLUSION: In DLB, RBD and sleep-wake disorders are common, heterogeneous, and complex, challenging their identification without performing V-PSG.

9.
Brain ; 142(3): 744-759, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30789229

RESUMO

Idiopathic REM sleep behaviour disorder (iRBD) is a powerful early sign of Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. This provides an unprecedented opportunity to directly observe prodromal neurodegenerative states, and potentially intervene with neuroprotective therapy. For future neuroprotective trials, it is essential to accurately estimate phenoconversion rate and identify potential predictors of phenoconversion. This study assessed the neurodegenerative disease risk and predictors of neurodegeneration in a large multicentre cohort of iRBD. We combined prospective follow-up data from 24 centres of the International RBD Study Group. At baseline, patients with polysomnographically-confirmed iRBD without parkinsonism or dementia underwent sleep, motor, cognitive, autonomic and special sensory testing. Patients were then prospectively followed, during which risk of dementia and parkinsonsim were assessed. The risk of dementia and parkinsonism was estimated with Kaplan-Meier analysis. Predictors of phenoconversion were assessed with Cox proportional hazards analysis, adjusting for age, sex, and centre. Sample size estimates for disease-modifying trials were calculated using a time-to-event analysis. Overall, 1280 patients were recruited. The average age was 66.3 ± 8.4 and 82.5% were male. Average follow-up was 4.6 years (range = 1-19 years). The overall conversion rate from iRBD to an overt neurodegenerative syndrome was 6.3% per year, with 73.5% converting after 12-year follow-up. The rate of phenoconversion was significantly increased with abnormal quantitative motor testing [hazard ratio (HR) = 3.16], objective motor examination (HR = 3.03), olfactory deficit (HR = 2.62), mild cognitive impairment (HR = 1.91-2.37), erectile dysfunction (HR = 2.13), motor symptoms (HR = 2.11), an abnormal DAT scan (HR = 1.98), colour vision abnormalities (HR = 1.69), constipation (HR = 1.67), REM atonia loss (HR = 1.54), and age (HR = 1.54). There was no significant predictive value of sex, daytime somnolence, insomnia, restless legs syndrome, sleep apnoea, urinary dysfunction, orthostatic symptoms, depression, anxiety, or hyperechogenicity on substantia nigra ultrasound. Among predictive markers, only cognitive variables were different at baseline between those converting to primary dementia versus parkinsonism. Sample size estimates for definitive neuroprotective trials ranged from 142 to 366 patients per arm. This large multicentre study documents the high phenoconversion rate from iRBD to an overt neurodegenerative syndrome. Our findings provide estimates of the relative predictive value of prodromal markers, which can be used to stratify patients for neuroprotective trials.

10.
Nat Rev Dis Primers ; 4(1): 19, 2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30166532

RESUMO

Rapid eye movement (REM) sleep behaviour disorder (RBD) is a parasomnia that is characterized by loss of muscle atonia during REM sleep (known as REM sleep without atonia, or RSWA) and abnormal behaviours occurring during REM sleep, often as dream enactments that can cause injury. RBD is categorized as either idiopathic RBD or symptomatic (also known as secondary) RBD; the latter is associated with antidepressant use or with neurological diseases, especially α-synucleinopathies (such as Parkinson disease, dementia with Lewy bodies and multiple system atrophy) but also narcolepsy type 1. A clinical history of dream enactment or complex motor behaviours together with the presence of muscle activity during REM sleep confirmed by video polysomnography are mandatory for a definite RBD diagnosis. Management involves clonazepam and/or melatonin and counselling and aims to suppress unpleasant dreams and behaviours and improve bedpartner quality of life. RSWA and RBD are now recognized as manifestations of an α-synucleinopathy; most older adults with idiopathic RBD will eventually develop an overt neurodegenerative syndrome. In the future, studies will likely evaluate neuroprotective therapies in patients with idiopathic RBD to prevent or delay α-synucleinopathy-related motor and cognitive decline.

11.
Sleep Med ; 52: 14-17, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30195197

RESUMO

BACKGROUND: The neuropathological hallmark of Parkinson's disease (PD) is the presence of aggregates of phosphorylated alpha-synuclein (pAS) in the nervous system. METHOD: We report a patient with video-polysomnography-confirmed idiopathic REM sleep behavior disorder that underwent parotidectomy because of parotid gland cancer. Immunohistochemistry of the gland tissue revealed abundant pAS deposits. One year after surgery the patient was diagnosed with PD. Prompted by this observation we examined the parotid gland in 10 consecutive individuals that underwent elective parotidectomy irrespective of their clinical condition. RESULTS: One had PD and another had mild parkinsonian signs plus reduced dopamine transporter uptake in the striatum. Both had pAS deposits in the parotid gland. The remaining eight subjects had no neurological signs and pAS was found in one of them. CONCLUSION: Our study shows that the parotid gland may contain pAS pathology in the prodromal stage of PD and in manifested PD.

12.
Sci Rep ; 8(1): 10628, 2018 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-30006563

RESUMO

Narcolepsy is a rare life-long disease that exists in two forms, narcolepsy type-1 (NT1) or type-2 (NT2), but only NT1 is accepted as clearly defined entity. Both types of narcolepsies belong to the group of central hypersomnias (CH), a spectrum of poorly defined diseases with excessive daytime sleepiness as a core feature. Due to the considerable overlap of symptoms and the rarity of the diseases, it is difficult to identify distinct phenotypes of CH. Machine learning (ML) can help to identify phenotypes as it learns to recognize clinical features invisible for humans. Here we apply ML to data from the huge European Narcolepsy Network (EU-NN) that contains hundreds of mixed features of narcolepsy making it difficult to analyze with classical statistics. Stochastic gradient boosting, a supervised learning model with built-in feature selection, results in high performances in testing set. While cataplexy features are recognized as the most influential predictors, machine find additional features, e.g. mean rapid-eye-movement sleep latency of multiple sleep latency test contributes to classify NT1 and NT2 as confirmed by classical statistical analysis. Our results suggest ML can identify features of CH on machine scale from complex databases, thus providing 'ideas' and promising candidates for future diagnostic classifications.

13.
Sleep ; 41(9)2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29986085

RESUMO

Study Objectives: To evaluate adherence to sodium oxybate prescribing information for indication and dosage, patients' compliance with instructions for use, safety/tolerability in routine clinical practice, and abuse potential. Methods: A postauthorization, noninterventional surveillance study (NCT00244465) in patients who were prescribed sodium oxybate according to current practice by sleep disorders specialists. Patients were monitored for ≤18 months. Results: Overall, 749 patients were enrolled; 730 included in the intent-to-treat population (narcolepsy type 1 n = 670, other indications n = 60). We report on patients with narcolepsy type 1 (female 47.9%, mean age 39.4 years); 495/670 (73.9%) completed the study. Median dose: at start of study 4.5 g per night, 6 g per night throughout study, in two equal doses. According to the treatment compliance checklist, 35.5 per cent of patients consumed alcohol, 19.3 per cent took the medication <2 hr after food, and 27.1 per cent did not adhere to recommended time schedule, with few associated treatment-emergent adverse events (TEAEs). Incidences of higher-than-recommended doses, difficulty in preparing doses, and abuse were low. TEAEs were reported by 67.3 per cent, most frequently headache (11.6%) and nasopharyngitis (6.4%). Discontinuation due to TEAEs: 8.8 per cent. Serious TEAEs: 6.4 per cent. There were no reports of respiratory depression. No particular safety concerns were identified in pediatric or elderly patients, or those with underlying sleep apnea. Conclusions: In this large postauthorization safety study of sodium oxybate use, indication and dosage prescribing recommendations were generally followed, and most patients complied with instructions, with deviations around alcohol consumption, eating before dosing and timing. The overall safety profile was consistent with previous observations; incidence of abuse was low. Section: Neurological disorders. Clinical Trial: Postauthorization, noninterventional, surveillance, pharmacoepidemiology study to evaluate long-term safety, tolerability, and compliance in administration of Xyrem (sodium oxybate) oral solution in patients who receive treatment with this medication in regular clinical practice. https://clinicaltrials.gov/ct2/show/NCT00244465, ClinicalTrials.gov: NCT00244465.

14.
Lancet Neurol ; 17(7): 574-576, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29866442
15.
Curr Neurol Neurosci Rep ; 18(7): 41, 2018 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-29796717

RESUMO

PURPOSE OF REVIEW: To review the clinical and polysomnographic features of the sleep disorder occurring in the recently described anti-IgLON5 disease. The hallmark of the disease is the presence of antibodies against IgLON5, a neural cell adhesion molecule of unknown function. The disease presents a robust HLA association, and the neuropathological examination shows a novel neuronal tauopathy with predominant hypothalamic and brainstem involvement. RECENT FINDINGS: Most patients (> 80%) present sleep-related vocalizations with movements and behaviors and sleep-disordered breathing. Polysomnographic studies show (1) a complex NREM sleep parasomnia at sleep initiation characterized by undifferentiated NREM or poorly structured N2 sleep with sleep-talking or mumbling, and simple or finalistic movements followed by normal periods of N3 or N2 NREM sleep, (2) REM sleep behavior disorder (RBD), and (3) obstructive sleep apnea with stridor. The last two features appear mainly in periods where NREM sleep normalizes. Identification of the anti-IgLON5 sleep disorder is important to suspect the disease. The combination of abnormal NREM sleep initiation, followed by normal periods of NREM sleep and RBD, represents a novel parasomnia.

16.
Cell Tissue Res ; 373(1): 245-266, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29846796

RESUMO

REM sleep is characterized by rapid eye movements, desynchronized electroencephalographic activity, dreams and muscle paralysis that preclude the individual from acting out the action of dreams. REM sleep is generated and modulated by a complex and still poorly understood, neuronal network that involves multiple nuclei and neurotransmission systems. The key structures that generate REM sleep muscle paralysis are the subcoeruleus nucleus in the mesopontine tegmentum and the reticular formation of the ventral medial medulla. Using glutamatergic, GABAergic and glycinergic inputs, direct and indirect projections from these two areas inhibit the motoneurons of the spinal cord resulting in skeletal paralysis in REM sleep. Experimental studies in cats and rodents where the subcoeruleus nucleus and ventral medial medulla were impaired by electrolytic, pharmacological and genetic manipulations have repeatedly produced increased electromyography activity during REM sleep associated with abnormal motor behaviors (e.g., prominent twitching, attack-like behaviors). These animal models represent the pathophysiological substrate of REM sleep behavior disorder, a parasomnia in humans characterized by nightmares and abnormal vigorous behaviors (e.g., prominent jerking, shouting, kicking) linked to excessive phasic and/or tonic electromyographic activity in REM sleep. The extraordinary observation that a sleep disorder is often the first manifestation of a devastating neurodegenerative disease such as Parkinson disease carries important diagnostic implications and opens a window for neuroprotection. This review addresses the neuronal substrates of REM sleep generation and modulation and how its impairment may lead to REM sleep behavior disorder.

17.
Sleep ; 41(8)2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29790977

RESUMO

Study Objectives: To assess whether biopsy of the labial minor salivary glands safely detects phosphorylated α-synuclein (pAS) deposits in idiopathic rapid eye movement sleep behavior disorder (IRBD), a condition that precedes the cardinal manifestations of synuclein disorders associated with Lewy-type pathology, namely, Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Methods: In a prospective study, labial biopsy of the minor salivary glands was performed in 62 patients with IRBD, 13 patients with PD, and 10 patients with DLB who were initially diagnosed with IRBD, and in 33 controls. Aggregates of pAS were assessed by immunohistochemistry using antiserine 129-pAS antibody and the conformation-specific 5G4 antibody. Results: Sufficient biopsy material containing glandular parenchyma was obtained in all participants. Deposits of pAS were found in 31 of 62 (50%) participants with IRBD, 7 of 13 (54%) with PD, 5 of 10 (50%) with DLB, and in one of the 33 (3%) controls. Participants with IRBD, PD, and DLB with and without pAS immunoreactivity did not differ in demographic and clinical features. Adverse events were lip bruising (9.2%), swelling (6.6%), pain (2.4%), and numbness (1.7%) which were mild and transitory and did not require treatment. Conclusions: Labial minor salivary glands biopsy proved to be a safe and useful procedure to identify pAS in participants with IRBD, and in participants with PD and DLB initially diagnosed with IRBD. The biopsy provides direct histopathological evidence that IRBD represents a synucleinopathy and that could be useful for histological confirmation of synuclein pathology in PD and DLB.

18.
Sleep ; 41(6)2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29554362

RESUMO

Study Objectives: To evaluate the utility of multimodal low-cost approaches including actigraphy, a wrist-worn device monitoring rest/activity cycles, in identifying patients with idiopathic REM sleep behavior disorder (iRBD). Methods: Seventy patients diagnosed with sleep disorders causing different motor manifestations during sleep (iRBD, sleep apnea, restless legs syndrome) and 20 subjects without any relevant motor manifestation during sleep, underwent video-polysomnography (vPSG) and 2 week actigraphy, completed six validated RBD screening questionnaires, and sleep apps use was assessed. Actigraphy was analyzed automatically, and visually by seven blinded sleep medicine experts who rated as "no," "possible," and "probable" RBD. Results: Quantitative actigraphy analysis distinguished patients from controls, but not between patients with different types of motor activity during sleep. Visual actigraphy rating by blinded experts in sleep medicine using pattern recognition identified vPSG confirmed iRBD with 85%-95% sensitivity, 79%-91% specificity, 81%-91% accuracy, 57.7% ± 11.3% positive predictive value, 95.1% ± 3.3% negative predictive value, 6.8 ± 2.2 positive likelihood ratio, 0.14 ± 0.05 negative likelihood ratio and 0.874-0.933 area under the ROC curve (AUC). AUC of the best performing questionnaire was 0.868. Few patients used sleep apps; therefore, their potential utility in the evaluated patients' groups is limited. Conclusions: Visual analysis of actigraphy using pattern recognition can identify subjects with iRBD, and is able to distinguish iRBD from other motor activities during sleep, even when patients are not aware of the disease in contrast to questionnaires. Therefore, actigraphy can be a reliable screening instrument for RBD potentially useful in the general population.

19.
Neurobiol Dis ; 115: 9-16, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29522818

RESUMO

BACKGROUND: The majority of patients diagnosed with idiopathic rapid eye movement sleep behaviour disorder (iRBD) progress over time to a Lewy-type α-synucleinopathy such as Parkinson's disease or dementia with Lewy bodies. This in vivo molecular imaging study aimed to investigate if extrastriatal monoaminergic systems are affected in iRBD patients and if this coincides with neuroinflammation. METHODS: We studied twenty-one polysomnography-confirmed iRBD patients with 18F-DOPA and 11C-PK11195 positron emission tomography (PET) to investigate extrastriatal monoaminergic function and microglial activation. Twenty-nine healthy controls (n = 9 18F-DOPA and n = 20 11C-PK11195) were also investigated. Analyses were performed within predefined regions of interest and at voxel-level with Statistical Parametric Mapping. RESULTS: Regions of interest analysis detected monoaminergic dysfunction in iRBD thalamus with a 15% mean reduction of 18F-DOPA Ki values compared to controls (mean difference = -0.00026, 95% confidence interval [-0.00050 to -0.00002], p-value = 0.03). No associated thalamic changes in 11C-PK11195 binding were observed. Other regions sampled showed no 18F-DOPA or 11C-PK11195 PET differences between groups. Voxel-level interrogation of 11C-PK11195 binding identified areas with significantly increased binding within the occipital lobe of iRBD patients. CONCLUSION: Thalamic monoaminergic dysfunction in iRBD patients may reflect terminal dysfunction of projecting neurons from the locus coeruleus and dorsal raphe nucleus, two structures that regulate REM sleep and are known to be involved in the early phase of PD. The observation of significantly raised microglial activation in the occipital lobe of these patients might suggest early local Lewy-type α-synuclein pathology and possibly an increased risk for later cognitive dysfunction.

20.
Parkinsonism Relat Disord ; 50: 94-98, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29487000

RESUMO

INTRODUCTION: Glucocerebrosidase (GBA) gene variants are associated with the development of the Lewy body disorders (LBD) Parkinson disease (PD) and dementia with Lewy bodies (DLB). Idiopathic REM sleep behavior disorder (IRBD) represents prodromal LBD in most instances. We investigated whether GBA variants are overrepresented in IRBD and if their presence shortens the time to conversion to clinically-defined LBD. METHODS: All GBA coding exons from 69 polysomnography-confirmed IRBD patients and 84 matched controls were sequenced by the Sanger method. RESULTS: Seven missense variants (E326K, L444P, A446T, A318G, R329C, T369M, N370S) were identified in eight (11.6%) IRBD patients and in one (1.2%) control (P = 0.026). After a mean follow-up of 8.9 ±â€¯3.8 years from IRBD diagnosis, five subjects with GBA variants developed LBD (3 DLB and 2 PD) and three remained disease-free. The risk of developing a LBD was similar in IRBD subjects with GBA variants than in those without variants (log rank test, p = 0.935). CONCLUSIONS: In IRBD, GBA variants are 1) more frequent when compared to controls, 2) associated with impending PD and DLB but 3) not indicative of a short-term risk for LBD after IRBD diagnosis. IRBD patients carrying GBA variants could be studied with disease-modifying interventions aiming to restore the GBA metabolic pathway.

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