Polysomnographic Evaluation of Sleep Disorders in Essential Tremor and Essential Tremor Plus: A Comparison With Healthy Controls
Article information
Abstract
Objective
To explore sleep patterns in individuals with essential tremor (ET) and essential tremor plus (ET-Plus) compared with healthy controls and assess differences between ET and ET-Plus, given the lack of established polysomnography (PSG) data on these groups and the potential for sleep disturbances to serve as clinical markers.
Methods
We conducted a prospective cross-sectional study at National Institute of Mental Health and Neurosciences, Bengaluru, from November 2021 to August 2023 on 45 patients (26 ET, 19 ET-Plus) and 45 controls. Tremor severity was assessed using The Essential Tremor Rating Assessment Scale (TETRAS) and Fahn‐Tolosa‐Marin Clinical Rating Scale (FTMRS). Sleep symptoms were assessed via the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Mayo Sleep Questionnaire, restless legs syndrome questionnaire, Berlin questionnaire, Generalized Anxiety Disorder Scale 7, and Patient Health Questionnaire-9. All patients and controls underwent overnight video PSG. Sleep scoring was manually performed by a trained sleep research technician and the first author following the American Academy of Sleep Medicine (2017) guidelines, with data analyzed using R studio.
Results
Compared with ET-Plus patients, ET patients had a younger onset age (46.8±11.1 years versus 30.8±16.7 years, respectively). Compared with ET patients, ET-Plus patients had higher TETRAS and FTMRS scores (p<0.005). Compared with controls, both ET patients and ET-Plus patients presented poorer sleep quality, excessive daytime sleepiness, rapid eye movement (REM) sleep behavior disorder, and restless legs syndrome symptoms. PSG findings supported these clinical observations, showing an elevated apnea‒hypopnea index, reduced total sleep time, prolonged REM latency, decreased sleep efficiency, increased N1 stage duration, and reduced N2/N3 durations and percentages in patients versus controls.
Conclusion
The study highlights significant sleep architecture abnormalities in both ET and ET-Plus patients compared with healthy controls, with no differences between the ET groups.
INTRODUCTION
Essential tremor (ET), the most common movement disorder in adults, is an isolated tremor syndrome with a distinct bilateral upper limb tremor (postural/action/kinetic) that persists for at least 3 years. Tremors may or may not involve tremors in other body parts, such as the lower limbs, head, voice, and tongue. However, it excludes explicitly isolated head or voice tremors. Recently, many ET patients have been reported to exhibit or develop additional neurological signs (soft signs) over time, such as subtle dystonic posturing, forgetfulness, and gait imbalance. A new term, “essential tremor plus” (ET-Plus), has been introduced to address such cases [1]. Compared with the ET group, the ET-Plus group is older at tremor onset, has lower educational attainment, and has a greater prevalence of head tremor, depression, anxiety, and probable rapid eye movement (REM) sleep behavior disorder (RBD) [2].
Similar to other neurodegenerative conditions, such as Parkinson’s disease (PD), ET patients may develop several nonmotor symptoms, including fatigue, anxiety, depression [3], cognitive difficulties, gait difficulties [3], and sleep disturbances [4], leading to significant disability in activities of daily living and an impact on health-related quality of life.
Sleep disturbances are common in PD and other synucleinopathies and ET. The underlying neurodegenerative process affects the brain’s sleep-regulating centers. ET is also proposed to be a neurodegenerative disease5 and is associated with many sleep abnormalities. The potential involvement of the locus coeruleus in sleep regulation and the observation of increased brainstem Lewy bodies in postmortem studies of individuals with ET compared with control brains may suggest a link to the development of sleep disturbances in ET [5].
The most common sleep disturbances observed in ET patients include poor sleep quality and excessive daytime somnolence [4,6-10]. ET patients also have restless legs syndrome (RLS) [11]. Studies have demonstrated that ET patients tend to score higher on sleep assessment scales such as the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) than control individuals do [6,7,9,12]. Insomnia and nocturia are not uncommon in ET patients [2,4,9]. RBD, though a pathognomonic feature of Parkinsonism and synucleinopathies, has also been described in ET patients in up to 23.5% of cases [13-15]. Polysomnographic studies by Salsone et al. [15] and Bugalho et al. [14] have shown that ET patients have polysomnography (PSG)-confirmed RBD.
PSG is useful for evaluating RBD and associated sleep disorders. Only a few PSG-based studies on ET have been carried out, and their results remain unequivocal. Through our study, we aimed to draw valid conclusions regarding sleep disturbances to clarify whether there are distinct sleep disturbances associated with ET and ET-Plus individuals compared with healthy individuals.
MATERIALS & METHODS
This study employed a cross-sectional observational design. Ethical approval was obtained from the institutional ethical committee ([NO. NIMH/DO/IEC][BS & NS Division]/2021-23). Informed consent form was obtained from the patients. We recruited participants over 2 years of age from individuals attending outpatient departments in the Department of Neurology and Movement Disorder Clinic at National Institute of Mental Health and Neurosciences Bengaluru. The inclusion criteria were patients aged 18 years or older, of both sexes, who were diagnosed with ET or ET-Plus based on the consensus statement on tremor classification by the International Parkinson and Movement Disorder Society task force criteria [1] and who were willing to participate in the study and overnight polysomnography. In this study, we recruited 45 ET patients (26 with ET and 19 with ETPlus) who consented to overnight polysomnography. Patients with parkinsonism, patients on tremor drugs such as valproate, beta adrenergic receptor agonists, antipsychotics (selective serotonin reuptake inhibitors), patients with hyperthyroidism and other systemic diseases that may impair sleep, patients with alcohol dependence (casual drinkers were not excluded), children (age <18 years), and pregnant women were excluded from this study. Additionally, a control group consisting of 45 healthy individuals with a negative family history of tremors, unaffected by tremors, sourced from patients’ spouses, hospital employees, acquaintances, and medical students, was recruited after providing consent for overnight PSG. We evaluated tremor severity and sleep profiles (using questionnaires and polysomnography) and compared the patient groups and healthy controls.
We collected detailed demographic and clinical data from all the participants, including age, sex, age of onset, disease duration, tremor response to alcohol, any associated comorbidities, and family history of ET. We conducted neurological examinations to differentiate between ET and ET-Plus and to assess tremors in the upper/lower limbs, head, voice, and tongue in resting, postural, and kinetic states. Soft neurological signs, including questionable dystonia, tandem gait impairment, bradykinesia, rigidity, oculomotor abnormalities, ataxia, primitive reflexes, forgetfulness, and mild cognitive impairment (MCI), were carefully examined as per the criteria mentioned by previous researchers and when there was a lack of consensus between the two examiners regarding their presence [16-18]. We assessed tremor severity via The Essential Tremor Rating Assessment Scale (TETRAS), which assesses daily living activities and performance. The Fahn‒Tolosa‒Marin Clinical Rating Scale (FTMRS) was used to assess the disability and severity of tremors.
After the inclusion of patients, clinical assessments of sleep disorders were performed to reveal their previous history of RLS, RBD, other parasomnias, insomnia, and sleep-disordered breathing. We assessed sleep disturbances using the PSQI, with a score more than 5 indicating poor sleep quality [19], the ESS for excessive daytime sleepiness [20], the Mayo Sleep Questionnaire (MSQ), for the assessment of RLS, the periodic limb movements (PLMs), the RBD, sleepwalking, obstructive sleep apnea (OSA), and sleeprelated leg cramps [21], the Berlin questionnaire for OSA risk22 and the International RLS Questionnaire to assess RLS severity [23]. The Generalized Anxiety Disorder Scale 7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used to assess anxiety and depression, respectively. Additionally, thyroid function tests, copper and ceruloplasmin levels, random blood sugars, and an magnetic resonance imaging (MRI) of the brain were performed to exclude alternative tremor causes.
Overnight video polysomnography was conducted according to the American Academy of Sleep Medicine (AASM 2017) guidelines using the SOMNOmedics 33-channel PSG system from Randersacker, Germany. The electrode application included 17 monopolar paste-based silver disc electrodes for electroencephalogram (EEG), two monopolar silver disc electrodes for electrooculography, and three silver disc electrodes for electromyography. The PSG data were preprocessed, including downsampling to 250 Hz and bandpass filtering (0.5–40 Hz). The converted “European data format” utilized manual scoring in 30-second epochs (aligned with the AASM 2017 guidelines). The sleep macroarchitecture parameters included time in bed, total sleep time (TST), wake after sleep onset (WASO), sleep onset latency (SOL), REM onset latency, duration and percentage of time in various sleep stages, and sleep efficiency. Wake, non-REM (N1, N2, N3), and REM stages were defined based on EEG patterns, eye movements, and muscle tone. The leg movements, periodic limb movements (PLMs) and apnea‒hypopnea indices involve specific criteria aligned with the AASM guidelines.
Statistical analysis
We entered the data in Microsoft Office Excel® (Microsoft Corp., Redmond, WA, USA), followed by R Studio version 2023 (Posit, Boston, MA, USA) for analysis. We checked the normality of the dataset using the Shapiro-Wilks test. Categorical variables were analyzed using the chi-square test for two groups and Pearson’s chi-square test for three groups. The Mann–Whitney U test was applied to skewed continuous data for two groups, whereas the Kruskal–Wallis test was used for three groups. Correlations between tremor scales and the sleep macroarchitecture parameters were assessed using Spearman’s rho, controlling for age. Post hoc adjustments were applied to analyze more than two groups using either Bonferroni correction or Tukey correction, and we reported the corresponding adjusted p values. The macroarchitecture data underwent logarithmic transformation to achieve a normal distribution, followed by analysis of covariance for sleep efficiency and other sleep parameters, with age used as a covariate. The linear regression model incorporated age and body mass index (BMI) as covariates to compare questionnaires between the ET and ET-Plus groups. If the p value is less than 0.05, it was used to determine the statistical significance for all analyses.
RESULTS
The ET-Plus patients in the current study were older than the ET patients. There was no significant difference in BMI between the groups (p value 0.641, 95% confidence interval upper 0.477, lower 0.359). In ET-Plus patients, head, voice, and lower limb tremors were significantly more common than in ET patients. The baseline characteristics of the patients and controls are presented in Table 1. Among 40 patients with ET, 30.0% (12 out of 40) reported alcohol consumption. Of these, 66.6% (8 out of 12) experienced an improvement in their tremors with alcohol, whereas 33.3% (4 out of 12) reported no effect.
Baseline demographics of patients and controls
Among the ET and ET-Plus patients, 100.0% had bilateral upper limb tremors. Lower limb tremors were more common in the ET-Plus patients (52.6%) than in the ET patients (26.9%) (p=0.079). Voice tremor and intention tremor were significantly greater in the ET-Plus patients (78.9% and 68.4%, respectively) than in the ET patients (42.3% and 30.7%), with p values of 0.014 and 0.012, respectively. Rest tremor was found in 36.8% of the ET-Plus cases but was absent in the ET cases (p<0.001). ET-Plus patients also presented additional soft signs, such as tandem gait impairment (57.8%), forgetfulness (47.3%), questionable dystonia (36.8%), and ataxia (10.5%) (Figure 1).
Types of tremors in ET and ET-Plus subjects. ET, essential tremor; ET-Plus, essential tremor plus.
A statistically significant difference was observed between the two groups when various subscores of both the TETRAS and the FTMRS tremor scales were compared (Table 1). Furthermore, ET patients and ET-Plus patients had significantly higher total ESS scores and global PSQI scores than healthy controls did (Table 1). RLS questionnaire scores were also higher in ET patients than in healthy controls (Table 1). These findings indicated that compared with healthy controls, ET patients experienced excessive sleepiness, poorer sleep quality, and more RLSs compared with healthy controls, but there was no significant difference between ET patients and ET-Plus patients. Compared with healthy controls, ET patients presented significantly higher rates of RBD and sleep apnea.
On further analysis, there were statistically significant differences in the MSQ scores for RBD, RLS, symptoms and Berlin questionnaire scores for sleep apnea across all groups (p<0.001), indicating worsened sleep symptoms in ET patients compared with healthy controls, with ET-Plus patients being the most affected. Compared with healthy controls, ET-Plus patients scored significantly higher on the GAD-7 questionnaire, indicating higher anxiety levels (Table 1). However, there was no significant difference in anxiety scores between ET patients and healthy controls or between ET patients and ET-Plus patients. Similarly, there was no significant difference in the depression score (PHQ-9) among the groups (Table 1).
Compared with healthy controls, ET and ET-Plus patients had significantly shorter sleep durations, significantly longer wake durations, and significantly longer WASO durations (Table 2). However, there was no statistically significant difference between ET patients and ET-Plus patients in terms of sleep duration, wake duration, wake percentage, or WASO. Compared with that of healthy controls, sleep efficiency was significantly lower in both ET patients and ET-Plus patients (Table 2, Figure 2A). However, there was no significant difference in sleep efficiency between the ET patients and the ET-Plus patients. There were no significant differences in N1 stage duration, N1 percentage or N2 duration between the groups (Table 2). However, the N2 stage percentage and N3 stage percentage were significantly lower in both the ET patients and the ET-Plus patients compared with healthy controls (Table 2, Figure 2C and D). However, there were no significant differences in these parameters between the ET patients and the ET-Plus patients. REM latency was significantly prolonged in both the ET patients and the ET-Plus patients compared with the healthy controls, with no significant difference between the ET patients and the ETPlus patients (Table 2). Compared with those in healthy controls, REM duration and percentage were reduced, and deep sleep latency was prolonged in both ET patients and ET-Plus patients; however, these differences were not statistically significant (Table 2, Figure 2B).
Sleep questionnaires and sleep macro architecture comparison between ET, ET-Plus and controls
Graph representing differences in sleep efficiency (A), REM percentage (B), stage 2 percentage(C), stage 3 percentage (D) between controls, ET and ET-Plus (blue: control, brown: ET, pink: ET-Plus). ET, essential tremor; ET-Plus, essential tremor plus; REM, reapid eye movement.
Compared with healthy controls, ET and ET-Plus patients had greater snoring and sleep apnea (as indicated by a significantly greater snore index and apnea‒hypopnea index [AHI]) and significantly greater arousal indices and PLM indices, with no significant difference between ET patients and ET-Plus patients (Table 2). Correlation analysis revealed significant associations between sleep parameters and tremor scale scores (TETRAS total score and FTMRS total score). The AHI and wake percentage were positively correlated, whereas the REM percentage was negatively correlated with both tremor scales. Additionally, positive correlations were found for REM latency and sleep latency, whereas negative correlations were observed for sleep efficiency and stage 3 percentage (Figure 3, Table 3).
Partial plot of correlation analysis of tremor scales scales in all patients including ET as well as ET-Plus patients and their sleep macro architecture. SOL, sleep onset latency; TETRAS, The Essential Tremor Rating Assessment Scale; REM, reapid eye movement; FTMRS, Fahn-Tolosa-Marin Clinical Rating Scale; RL, REM latency; WASO, wake after sleep onset; SE, sleep efficiency; ET, essential tremor; ET-Plus, essential tremor plus.
Correlation analysis of tremor severity scales in all patients including ET as well as ET-Plus patients and their sleep macro-architecture
In total, 12 (26.7%) of 45 patients had RBD symptoms according to the RBD screening questionnaire. We extensively evaluated the REM stages in the polysomnography of these patients. Among the 12 patients, 4 patients (33.3%) had REM confirmed by polysomnography. In the remaining 8 patients, although their bed partners complained of REM behavior symptoms, this symptom was not detected via polysomnography. However, none of the controls had REM behavior disorders according to polysomnography. Among the 4 patients who had polysomnogram-confirmed RBD, 3 were ET-Plus, whereas one ET patient had RBD (Figure 4).
Characteristics of 4 patients (1 ET and 3 ET-Plus) with RBD in polysomnography. TETRAS, The Essential Tremor Rating Assessment Scale; FTMRS, Fahn-Tolosa-Marin Clinical Rating Scale; ET, essential tremo; ETP, essential tremor plus; RBD, rapid eye movement sleep behavior disorder; PSQI, Pittsburgh Sleep Quality Index; ESS, Epworth Sleepiness Scale.
Regression analyses were conducted to examine various factors related to ET and its impact on sleep and tremor severity. Age and age at onset did not significantly influence tremor severity in ET versus ET-Plus, suggesting that tremor severity in ET is independent of age-related factors. Age had a less pronounced effect on sleep quality, with ESS scores being a significant predictor. Trends suggesting a greater risk of sleep apnea in the ETPlus group were observed but were not statistically significant. Both BMI and ET-Plus were significant predictors of excessive daytime sleepiness. A significant positive relationship between BMI and the AHI was found, indicating that a higher BMI was associated with a higher AHI.
DISCUSSION
Our study investigated sleep disturbances in patients with ET via polysomnography. Specifically, we explored disrupted patterns of sleep parameters and assessed sleep quality in ET patients. In parallel, a systematic review was conducted by Jiménez-Jiménez et al. [4] into the realm of sleep disorders in ET patients, with a particular emphasis on examining findings from polysomnographic studies. Recent studies suggest an association between ET and sleep abnormalities, potentially linked to shared neurotransmitter pathways in the brainstem. Our study aims to explore sleep disturbances in both ET and ET-Plus patients.
Demography, tremor characteristics, and additional soft neurological signs
In our study, the earliest age of onset of tremors was 10 years, and the eldest age of onset was 70 years, indicating a bimodal age of onset of tremors in ET. This finding is consistent with a meta-analysis by Song et al. [24], which also revealed a similar bimodal age of onset among ET patients. Among the cases examined in our study, 57.7% were ET cases, and 42.2% were ETPlus cases, differing from the findings of a Chinese survey (47.1% as ET cases) [18]. Conversely, our findings align closely with those of Lolekha et al. [25], who reported 52.9% ET. Consistent with prior investigations, ET patients had an earlier age of onset than did ET-Plus patients in our cohort [18,26]. ET-Plus patients had higher cranial tremor rates than ET patients did, which is consistent with prior research showing more head tremors in ET-Plus [25,26].
In our study, ET-Plus patients showed tandem gait impairment as the most common sign, followed by mild memory issues and questionable dystonic posturing. This aligns with prior research indicating higher rates of cognitive impairment and dystonia in ET-Plus than in ET [4,25]. Rest tremors were observed in 36.8% of the ET-Plus patients, all of whom had significant postural tremors without bradykinesia, rigidity, or postural hypotension, excluding PD. Erro et al. [27] suggested that ET-Plus resting tremor could represent a late feature of ET, a different disorder with later onset and lower genetic susceptibility, early PD, or a misdiagnosis of ET. Compared with ET patients, ET-Plus patients presented higher TETRAS and FTMRS scores, indicating more severe impairment in daily activities and tremor severity, similar to previous investigations [26].
Sleep disturbances in ET patients and ET-Plus patients
Statistically significant differences were observed in the total ESS, total global PSQI, and RLS questionnaire scores between ET patients (both ET patients and ET-Plus patients) and healthy controls, indicating increased daytime sleepiness, poor sleep quality, and increased RLSs. Chandran et al. [3] reported a mean PSQI of 5.9±4.6 in ET patients compared with controls, who had a mean PSQI of 2.6±2.3. Consistently, several studies reported significantly poorer sleep and higher PSQI scores in ET patients than in healthy controls [6,9,10]. However, few studies have reported no significant difference in the sleep quality of ET patients compared with healthy controls [7]. Importantly, even in these two studies, mean PSQI scores were higher in ET patients than in healthy controls. We did not observe a significant difference in sleep questionnaires between ET patients and ET-Plus patients.
We observed significant differences in RBD, RLS, and sleep apnea between ET patients and healthy controls. Research has shown that individuals with ET commonly show increased symptoms of both RBD and RLS [2,13,15]. However, a study conducted by Wu et al. [28] on a comprehensive population-based door-todoor screening revealed an absence of association between RBD and ET in their findings.
A population-based study revealed RLS in 16.7% of ET patients, which was significantly greater than that reported in controls [28]. Hence, we infer that ET patients suffer from sleep abnormalities apart from the motor disability that they have.
Polysomnography findings in ET patients and ET-Plus patients
Video PSG is a useful test for objectively evaluating sleep. However, studies assessing polysomnographic sleep macroarchitecture in individuals with ET are limited due to low participation rates and small sample sizes. Overnight PSG studies in MCI have revealed macroarchitecture abnormalities, including increased WASO, delayed REM sleep latency, and reduced REM and slow-wave sleep durations, possibly linked to cognitive decline [29]. While the literature on sleep architecture in ET is limited, research on other movement disorders, such as progressive supranuclear palsy, has shown reduced TST; shorter durations of stages N2, N3, and REM sleep; lower sleep efficiency; increased wake durations; WASO percentages; and increased latencies for stages N2 and N3 [30]. Similar results were obtained in our evaluation of ET patients, where we observed shorter sleep duration, prolonged wake duration, increased wake percentage, increased arousal, prolonged REM latency, reduced N2 and N3 percentages, and diminished sleep efficiency, indicating poor sleep quality and difficulty achieving deeper sleep stages compared with healthy controls. However, the differences between ET and ET-Plus were not significant. Barut et al.’s [9] PSG study revealed that compared with PD patients, ET patients had lower mean oxygen saturation and increased occurrence of REM without atonia and increased WASO; however, there were no significant differences in sleep efficiency, the AHI, arousal indices, or the PLM index among individuals with PD or ET and control individuals. Conversely, the ET patients in our study had more snoring, sleep apnea, and significantly more PLMs than did the healthy controls. Confirming sleep abnormalities via polysomnography strengthens the association of sleep abnormalities in our patient group.
The impact of our findings on ET-Plus
Our findings revealed an age distinction between ET patients and ET-Plus patients, with ET-Plus individuals presenting symptoms nearly a decade later. In contrast to the belief that ET-Plus represents a progression of ET with soft signs emerging later, our findings challenge this view. We observed soft signs in ETPlus patients as young as their 20s or 30s, indicating that age alone may not reliably indicate this continuum hypothesis. ETPlus patients exhibited greater disability and tremor severity, indicating a more advanced stage of ET. While it remains to be seen whether these ET-Plus patients initially presented as such or developed into this category later, labeling both subsets similarly is unjustified. To address the notion that ET-Plus may be associated with age-related progression, we reanalyzed tremor severity while considering age and age at onset as confounding factors. We found that patients in the ET-Plus group consistently exhibited greater disease severity than those in the ET group.
In essence, our research contributes valuably to the ongoing debate on the differences between ET and ET-Plus and introduces a novel dimension by shedding light on sleep abnormalities in ET patients, a facet that has yet to receive detailed scrutiny in prior studies.
Strengths and limitations
This is the first study to comprehensively examine and compare sleep patterns and polysomnographic findings between patients with ET and those with ET-Plus. We conducted MRI brain scans in ET patients to exclude secondary causes of tremors, although incorporating Dopamine Transporter Scan could have strengthened the study. This is an observational study; longitudinal data would be more interesting if initial sleep abnormalities had an impact on disease progression. Given the prevalence of ET, our sample size was relatively small.
Conclusions
The evaluation of ET and its subset, ET-Plus, revealed significant differences in motor and nonmotor scores. Compared with ET patients, ET-Plus patients presented worse functional outcomes, greater tremor severity, and greater disability. Compared with healthy controls, both the ET and ET-Plus groups presented significantly more prevalent sleep disturbances. PSG findings highlighted compromised sleep architecture in ET patients. Understanding and addressing sleep dysfunction emerges as a crucial aspect of comprehensive care, offering potential avenues for improving overall outcomes in this patient population.
Notes
Conflicts of Interest
The authors have no financial conflicts of interest.
Funding Statement
None
Author Contributions
Conceptualization: Ravi Prakash Singh, Doniparthi Venkata Seshagiri, Rohan Mohale, Pramod Kumar Pal, Bindu M Kutty, Jitender Siani, Nitish L Kamble, Vikram Holla, Ravi Yadav. Data Curation: Ravi Prakash Singh, Mythirayee S, Ravi Yadav. Formal Analysis: Ravi Prakash Singh, Mythirayee S, Gulshan Kumar, Ravi Yadav. Investigation: Ravi Prakash Singh, Doniparthi Venkata Seshagiri, Rohan Mohale, Pramod Kumar Pal, Nitish L Kamble, Vikram Holla, Ravi Yadav. Methodology: Ravi Prakash Singh, Mythirayee S, Ravi Yadav. Project Administration: Ravi Prakash Singh, Ravi Yadav. Resources: Ravi Yadav. Software: Ravi Prakash Singh, Mythirayee S, Gulshan Kumar. Supervision: Doniparthi Venkata Seshagiri, Rohan Mohale, Pramod Kumar Pal, Nitish L Kamble, Vikram Holla, Ravi Yadav. Validation: Ravi Yadav. Visualization: Ravi Prakash Singh, Mythirayee S, Gulshan Kumar, Ravi Yadav. Writing—original draft: Ravi Prakash Singh, Mythirayee S, Ravi Yadav. Writing—review & editing: Ravi Prakash Singh, Mythirayee S, Ravi Yadav.
Acknowledgements
The authors would like to express their sincere gratitude to the Department of Neurology and the Movement Disorders Clinic at the National Institute of Mental Health and Neurosciences, Bengaluru, for their invaluable support in conducting this study. We extend our heartfelt thanks to the patients and healthy volunteers who participated in this research and made this study possible.
Special thanks to the sleep research technicians for their meticulous efforts in polysomnography data acquisition and analysis.
Lastly, we are grateful to our colleagues and mentors for their guidance and to the institutional ethics committee for their approval and oversight.