RestEaze: An Emerging Technology to Characterize Leg Movements During Sleep

Several sleep disorders are characterized by periodic leg movements during sleep including Restless Leg Syndrome, and can indicate disrupted sleep in otherwise healthy individuals. Current technologies to measure periodic leg movements during sleep are limited. Polysomnography and some home sleep tests use surface electromyography to measure electrical activity from the anterior tibilias muscle. Actigraphy uses 3-axis accelerometers to measure movement of the ankle. Electromyography misses periodic leg movements that involve other leg muscles and is obtrusive because of the wires needed to carry the signal. Actigraphy based devices require large amplitude movements of the ankle to detect leg movements (missing the significant number of more subtle leg movements) and can be worn in multiple configurations precluding precision measurement. These limitations have contributed to their lack of adoption as a standard of care for several sleep disorders. In this study, we develop the RestEaze sleep assessment tool as an ankle-worn wearable device that combines capacitive sensors and a 6-axis inertial measurement unit to precisely measure periodic leg movements during sleep. This unique combination of sensors and the form-factor of the device addresses current limitations of periodic leg movements during sleep measurement techniques. Pilot data collected shows high correlation with polysomnography across a heterogeneous participant sample and high usability ratings. RestEaze shows promise in providing ecologically valid, longitudinal measures of leg movements that will be useful for clinicians, researchers, and patients to better understand sleep.

Chorea, Ataxia, and Disturbed Sleep

A 72-year-old man sought care for predominant choreiform movements, mild gait ataxia, urinary dysfunction, and abnormal nocturnal behaviors. Choreiform movements were nearly constant while awake, vanished during sleep, and predominantly involved his lower extremities and trunk. He also had urinary dysfunction, with urinary hesitancy and frequency. Sleep-related behaviors included sleep talking, sleep singing, sudden single-limb jerking movements, and complex hand movements. He also had daytime sleepiness. On neurologic examination, abnormal findings included postural instability at baseline with eyes open and a slightly wide-based tentative gait and inability to execute tandem walking. He had intermittent choreiform movements of the legs and the left shoulder. He also had occasional repetitive, periodic, voluntary-appearing, triple flexion–type movements of both legs. Overnight polysomnography was ordered to evaluate nocturnal movements. Polysomnography revealed rapid periodic leg movements of sleep and rapid eye movement sleep without atonia. Sleep architecture was mildly deranged, with electroencephalographic alpha intrusion throughout nonrapid eye movement sleep, as well as absent slow-wave sleep. Ferritin level was suboptimal. Evaluation of serum for autoimmune encephalitis demonstrated IgLON family member 5 antibody positivity by tissue immunofluorescence assay, confirmed by cell-based assay. The patient was diagnosed with IgLON family member 5 autoimmune encephalitis and symptomatic rapid eye movement sleep behavior disorder. The patient was instructed to maintain a safe sleep environment at home and to begin taking melatonin at bedtime. A therapeutic trial of intravenous methylprednisolone, together with mycophenolate mofetil, was followed by improvement in memory, confusion, and hallucinations, waking involuntary movements, bladder dysfunction, and sleep quality. Rapid eye movement sleep behavior disorder is a parasomnia characterized by rapid eye movement sleep without atonia, the loss or dysregulation of normal rapid eye movement sleep atonia, which is its pathophysiologic signature, and which is permissive for dream enactment behaviors during rapid eye movement sleep.

Polysomnographic correlates of sleep disturbances in de novo, drug naïve Parkinson’s Disease

Background Sleep disturbances are common non-motor symptoms of Parkinson’s Disease (PD). Methods The aim of this study was to investigate the polysomnographic correlates of sleep changes, as investigated by the Parkinson’s Disease Sleep Scale-2 (PDSS-2), in a cohort of sixty-two consecutive de novo, drug naïve PD patients (71.40 ± 7.84 y/o). Results PDSS-2 total score showed a direct correlation with stage shifts (p = 0.008). Fragmented sleep showed an inverse correlation with sleep efficiency (p = 0.012). Insomnia symptoms showed an inverse correlation with wake after sleep onset (p = 0.005) and direct correlation with periodic leg movements (p = 0.006) and stage shift indices (p = 0.003). Motor Symptoms showed a direct correlation with Apnoea-Hypopnoea (AHI; p = 0.02) and awakenings indices (p = 0.003). Dream distressing showed a direct correlation with REM without atonia (RWA, p = 0.042) and an inverse correlation with AHI (p = 0.012). Sleep quality showed an inverse correlation with RWA (p = 0.008). Conclusion PDSS-2 features are significantly correlated with polysomnography objective findings, thus further supporting its reliability to investigate sleep disturbances in PD patients.

White matter tract-specific alterations in patients with primary restless legs syndrome

Prior diffusion tensor imaging (DTI) studies have investigated white matter (WM) changes in patients with primary restless legs syndrome (RLS), but the results were inconsistent. Here, we proposed using tract-specific statistical analysis (TSSA) to find alterations in specific WM tracts to clarify the pathophysiological mechanisms of RLS. We enrolled 30 patients with RLS and 31 age- and sex- matched controls who underwent brain magnetic resonance imaging, neuropsychological tests, and polysomnography. Fractional anisotropy (FA) maps obtained from whole-brain diffusion tensor imaging and TSSA were used to localize WM changes in patients with RLS. Subsequently, a comparison of FA values for each tract between patients and controls was performed. The associations between FA values and clinical, polysomnographic, and neuropsychological parameters in RLS patients were assessed. RLS patients demonstrated decreased FA values in the left corticospinal tract (CST) and cingulum, and in the right anterior thalamic radiation (ATR) and inferior fronto-occipital fasciculus (IFO). Patients’ attention/executive function and visual memory scores positively correlated with FA values in the right ATR, and anxiety levels negatively correlated with FA values in the right IFO. Additionally, the number of periodic leg movements and movement arousal index were negatively correlated with FA values in the left CST. The TSSA method identified previously unknown tract-specific alterations in patients with RLS and significant associations with distinct clinical manifestations of RLS.

Association of Central Hypersomnia and Fatigue in Patients With Multiple Sclerosis: A Polysomnographic Study

Objective:To evaluate sleepiness and central hypersomnia in multiple sclerosis (MS) associated fatigue, we performed long term polysomnography in MS patients and healthy controls.Methods:Patients with MS and healthy controls completed questionnaires on sleep, fatigue, sleepiness, and depression. They underwent nocturnal polysomnography, multiple sleep latency tests and bed rest 24-hour polysomnography. Patients were divided into 3 groups (fatigue and sleepiness; fatigue and no sleepiness; neither fatigue nor sleepiness).Results:Among 44 patients with MS, 19 (43.2%) had fatigue and sleepiness, 15 (34%) had only fatigue, and 10 (22.7%) had neither fatigue nor sleepiness. Compared to 24 controls, patients with fatigue and sleepiness had higher REM sleep percentages (median [interquartile range]: 20.5% [19.6-24.7] vs. 18.1% [12.6-20.6]), lower arousal indexes (12.7 [7.5-17.0] vs. 22.4 [14.3-34.4]) and shorter daytime mean sleep latencies (8.6 [6.3-14.3] vs. 16.6 [12.6-19.5] min). Restless leg syndrome, periodic leg movements and sleep apnea had similar frequencies between groups. Central hypersomnia was found in 10 (53%) patients with fatigue and sleepiness (narcolepsy type 2, N=2), in 2 (13%) patients with fatigue only, and in 3 (30%) patients with neither fatigue nor sleepiness. Patients with central hypersomnia were younger and sleepier than those without hypersomnia, but had similar levels of fatigue, disability, depression, cognitive performance and frequencies of the human leukocyte antigen DQB1*0602 genotype. The severity of fatigue increased with higher depression scores, higher sleepiness severity, and lower sleep efficacy.Conclusion:Central hypersomnias are frequent in MS when fatigue and sleepiness are present. Screening them through polysomnography studies is recommended.

CASPR-2 related morvan’s syndrome: Autonomic, polysomnographic & neuropsychological observations

Background& Objectives:Morvan’s syndrome is characterized by central, autonomic, and peripheral hyperexcitability due to CASPR-2-antibody. Our objective was to study the clinical spectrum, electrophysiological, autonomic, polysomnographic and neuropsychological profile in patients of CASPR-2 related Morvan’s syndrome.Materials & Methods:Serum and CSF samples that were CASPR2-antibody positive from 2016-2019 were assessed. Among them, patients of Morvan’s syndrome diagnosed based on clinical and electrophysiological basis were included.Results:14(M: F-10:4) patients of Morvan’s syndrome were included with age at onset of 37.1±17.5 years. The clinical features were muscle twitching (12), insomnia (12), pain (11), paraesthesias (9), hyperhidrosis (7), hypersalivation (6), double incontinence (3), spastic speech (2), dysphagia (2), behavioral disturbances (2), seizures (1) cold intolerance (1). Neurological examination revealed myokymia (12), hyperactive tendon reflexes (10), tremor (6). Electromyogram revealed neuromyotonia (12) and increased spontaneous activity (7). Autonomic function tests conducted in eight patients revealed definite autonomic dysfunction (4), orthostatic hypotension (2), early dysfunction (1) and postural orthostatic tachycardia syndrome (1). Polysomnography findings done in six patients revealed insomnia (3), absence of deep sleep (1), high frequency beta activity (1), REM (rapid eye movement) behaviour disorder(1), periodic leg movements(1). Neuropsychological evaluation showed subtle involvement of the left frontal and temporal lobe. Malignancy workup was negative. All patients were treated with steroids. There was complete neurological resolution in follow-up with persistent neuropathic pain in five patients.Conclusions:This study has contributed to the growing knowledge on CASPR2-related Morvan’s syndrome. It is important for an increased awareness and early recognition as it’s potentially treatable by immunotherapy.