1Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India
2Centre for Consciousness Studies, Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Bengaluru, India
3Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, India
Copyright © 2025 The Korean Movement Disorder Society
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Baseline characteristics | ET (n=26) | ET-Plus (n=19) | Controls (n=45) | p value |
---|---|---|---|---|
Age (yr) | 43.12±15.30 | 58.05±11.17 | 40.82±9.23 | <0.001* |
Age at onset (yr) | 30.81±16.73 | 46.83±11.12 | N/A | <0.001† |
Duration of illness (yr) | 12.7±6.91 | 11.3±8.53 | N/A | 0.346† |
BMI (kg/m2) | 24.3±3.33 | 22.9±6.52 | 24.5±3.70 | 0.641* |
Males | 18 (69.2) | 12 (63.1) | 31 (68.8) | N/A |
Females | 8 (30.7) | 7 (36.8) | 14 (31.1) | N/A |
Positive family history | 12 (46.1) | 8 (42.1) | N/A | 0.787‡ |
Tremor scales | ||||
TETRAS total score (out of 112) | 45.08±15.32 | 59.95±17.13 | N/A | 0.004† |
TETRAS ADL subscale (out of 48) | 18.42±8.33 | 24.68±8.37 | N/A | 0.017† |
TETRAS performance subscale (out of 64) | 26.62±7.83 | 35.32±9.08 | N/A | 0.001† |
FTMRS total score (out of 144) | 34.85±12.26 | 57.32±26.17 | N/A | <0.001† |
FTMRS severity percent (total score by maximum possible score) | 24.19±8.62 | 39.79±18.25 | N/A | <0.001† |
FTMRS disability level | 1.54±0.58 | 2.16±0.83 | N/A | 0.005† |
Sleep questionnaires | ||||
Global PSQI scores | 5.23 (1–14) | 7.68 (2–18) | 4 (0–6) | <0.001§, <0.001ǁ, 0.376¶ |
ESS total score | 4.15 (0–16) | 5.95 (0–15) | 2 (0–14) | <0.001§, <0.001ǁ, 0.230¶ |
RLS-Q score | 0 (0–17) | 2 (0–20) | 0 (0–1) | <0.001§, <0.001ǁ, 0.131¶ |
Anxiety and depression questionnaires | ||||
GAD-7 score | 4 (1–11) | 5 (1–14) | 3 (0–9) | 0.069§, 0.005ǁ, 0.603¶ |
PHQ-9 score | 4 (1–17) | 4 (1–14) | 4 (1–9) | 0.922§, 0.873ǁ, 0.908¶ |
Tremor characteristics of ET and ET-Plus. Values are presented as mean±standard deviation number (%), or median (interquartile range) unless otherwise indicated.
* indicates the use of ANOVA;
† the statistical test used is the Student t-test;
‡ the chi-square test was used for categorical variables;
§ ET versus control;
ǁ ET-Plus versus control;
¶ ET versus ET-Plus.
ET, essential tremor; ET-Plus, essential tremor plus; BMI, body mass index; TETRAS, The Essential Tremor Rating Assessment Scale; ADL, activities of daily living; FTMRS, Fahn-Tolosa-Marin Clinical Rating Scale; PSQI, Pittsburgh Sleep Quality Index; ESS, Epworth Sleepiness Scale; RLS-Q, restless legs syndrome questionnaire; GAD-7, Generalized Anxiety Disorder Scale 7; PHQ-9, Patient Health Questionnaire-9; N/A, not applicable; ANOVA, analysis of variance.
Sleep macroarchitecture | ET (n=26) (median with IQR) | ET-Plus (n=19) (median with IQR) | Controls (n= 45) (median with IQR) | Kruskal– Wallis χ2 | Pairwise comparison p value |
---|---|---|---|---|---|
TIB (minutes) | 539 (454, 601) | 482 (380, 600) | 497 (332, 549) | 14.881 | <0.001*, 0.01†, 0.619‡ |
Sleep period (minutes) | 476 (318, 587) | 480 (124, 513) | 458 (285, 602) | 1.534 | 0.583*, 0.993†, 0.554‡ |
Sleep duration (minutes) | 343 (162, 568) | 344 (87, 427) | 429 (206, 563) | 18.441 | <0.013*, <0.001†, 0.869‡ |
Wake duration (minutes) | 178 (14, 355) | 165 (72, 450) | 57.4 (8, 254) | 33.834 | <0.001*, <0.001†, 0.997‡ |
Wake percentage | 35.7 (2.5, 65.9) | 31.4 (14.5, 83.8) | 12.4 (1.82, 45.7) | 29.386 | <0.001*, <0.001†, 0.952‡ |
WASO | 141 (12, 266) | 133 (32, 400) | 12 (2, 46) | 54.421 | <0.001*, <0.001†, 0.945‡ |
Sleep latency (minutes) | 20 (2, 207) | 17 (2, 74) | 13 (1, 94) | 3.915 | 0.169*, 0.395†, 0.846‡ |
Sleep efficiency (%) | 70.2 (17.4, 85.5) | 64.2 (34.4, 97.5) | 87.4 (54.3, 98.8) | 29.884 | <0.001*, <0.001†, 0.959‡ |
AHI | 7 (0, 73) | 5 (0, 45) | 4 (0, 11) | 34.842 | <0.001*, <0.001†, 0.776‡ |
Arousal index | 152 (1, 352) | 83 (2, 213) | 5 (0, 87) | 36.912 | <0.001*, <0.001†, 0.133‡ |
PLM index | 4 (0, 107) | 7 (0, 105) | 2 (0,12) | 13.443 | 0.002*, <0.001†, 0.776‡ |
Snore index | 0 (0, 3,779) | 1 (0, 2,534) | 0 (0, 0.0293) | 11.628 | 0.001*, 0.002†, 0.751‡ |
N1 duration (minutes) | 44 (15, 142) | 33 (20, 116) | 31 (2, 175) | 4.183 | 0.159*, 0.966†, 0.317‡ |
N1 percentage | 8 (3, 24) | 7 (4, 22) | 10 (0, 28) | 0.514 | 0.815*, 0.846†, 0.993‡ |
N2 duration (minutes) | 193 (57, 310) | 197 (61, 291) | 177 (0, 368) | 3.723 | 0.267*, 0.255†, 0.959‡ |
N2 percentage | 36 (13, 56) | 39 (11, 54) | 54 (12, 166) | 20.529 | <0.001*, 0.042†, 0.643‡ |
N3 duration (minutes) | 51 (0, 106) | 30 (0, 82) | 71 (0, 164) | 12.973 | 0.057*, 0.023†, 0.316‡ |
N3 percentage | 10 (0, 20) | 6 (0, 16) | 15 (0, 68) | 10.722 | 0.094*, 0.006†, 0.484‡ |
REM duration (minutes) | 53 (7, 149) | 53 (0, 120) | 66 (0, 177) | 0.311 | 0.928*, 0.923†, 0.890‡ |
REM percentage | 9 (1, 29) | 10 (0, 23) | 15 (0, 42) | 3.326 | 0.362*, 0.235†, 0.995‡ |
REM latency (minutes) | 138 (9, 358) | 116 (55, 445) | 81 (5, 281) | 14.598 | 0.024*, 0.016†, 0.962‡ |
Deep sleep latency (minutes) | 82 (19, 440) | 68 (28, 294) | 53 (7, 325) | 5.046 | 0.123*, 0.222†, 0.969‡ |
Sleep parameters of ET as a whole including ET and ET-Plus* |
TETRAS total score |
FTMRS total score |
||
---|---|---|---|---|
Spearman’s rho | p value | Spearman’s rho | p value | |
AHI sleep | 0.589 | <0.001 | 0.573 | <0.001 |
Sleep period | -0.592 | <0.001 | 0.298 | 0.049 |
Wake duration | 0.348 | 0.022 | 0.439 | 0.003 |
Wake percentage | 0.336 | 0.028 | 0.448 | 0.003 |
WASO | -0.765 | <0.001 | 0.842 | <0.001 |
REM percentage | -0.419 | 0.005 | -0.195 | 0.206 |
REM latency (minute number) | 0.453 | 0.002 | 0.426 | 0.004 |
Sleep latency | 0.587 | <0.001 | 0.382 | 0.011 |
Sleep efficiency | -0.979 | <0.001 | -0.686 | <0.001 |
Stage N1 percentage | 0.227 | 0.139 | -0.241 | 0.115 |
Stage N2 percentage | -0.082 | 0.605 | -0.159 | 0.303 |
Stage N3 percentage | -0.366 | <0.001 | -0.105 | 0.499 |
Comments on this article
Baseline characteristics | ET (n=26) | ET-Plus (n=19) | Controls (n=45) | p value |
---|---|---|---|---|
Age (yr) | 43.12±15.30 | 58.05±11.17 | 40.82±9.23 | <0.001 |
Age at onset (yr) | 30.81±16.73 | 46.83±11.12 | N/A | <0.001 |
Duration of illness (yr) | 12.7±6.91 | 11.3±8.53 | N/A | 0.346 |
BMI (kg/m2) | 24.3±3.33 | 22.9±6.52 | 24.5±3.70 | 0.641 |
Males | 18 (69.2) | 12 (63.1) | 31 (68.8) | N/A |
Females | 8 (30.7) | 7 (36.8) | 14 (31.1) | N/A |
Positive family history | 12 (46.1) | 8 (42.1) | N/A | 0.787 |
Tremor scales | ||||
TETRAS total score (out of 112) | 45.08±15.32 | 59.95±17.13 | N/A | 0.004 |
TETRAS ADL subscale (out of 48) | 18.42±8.33 | 24.68±8.37 | N/A | 0.017 |
TETRAS performance subscale (out of 64) | 26.62±7.83 | 35.32±9.08 | N/A | 0.001 |
FTMRS total score (out of 144) | 34.85±12.26 | 57.32±26.17 | N/A | <0.001 |
FTMRS severity percent (total score by maximum possible score) | 24.19±8.62 | 39.79±18.25 | N/A | <0.001 |
FTMRS disability level | 1.54±0.58 | 2.16±0.83 | N/A | 0.005 |
Sleep questionnaires | ||||
Global PSQI scores | 5.23 (1–14) | 7.68 (2–18) | 4 (0–6) | <0.001 |
ESS total score | 4.15 (0–16) | 5.95 (0–15) | 2 (0–14) | <0.001 |
RLS-Q score | 0 (0–17) | 2 (0–20) | 0 (0–1) | <0.001 |
Anxiety and depression questionnaires | ||||
GAD-7 score | 4 (1–11) | 5 (1–14) | 3 (0–9) | 0.069 |
PHQ-9 score | 4 (1–17) | 4 (1–14) | 4 (1–9) | 0.922 |
Sleep macroarchitecture | ET (n=26) (median with IQR) | ET-Plus (n=19) (median with IQR) | Controls (n= 45) (median with IQR) | Kruskal– Wallis χ2 | Pairwise comparison p value |
---|---|---|---|---|---|
TIB (minutes) | 539 (454, 601) | 482 (380, 600) | 497 (332, 549) | 14.881 | <0.001 |
Sleep period (minutes) | 476 (318, 587) | 480 (124, 513) | 458 (285, 602) | 1.534 | 0.583 |
Sleep duration (minutes) | 343 (162, 568) | 344 (87, 427) | 429 (206, 563) | 18.441 | <0.013 |
Wake duration (minutes) | 178 (14, 355) | 165 (72, 450) | 57.4 (8, 254) | 33.834 | <0.001 |
Wake percentage | 35.7 (2.5, 65.9) | 31.4 (14.5, 83.8) | 12.4 (1.82, 45.7) | 29.386 | <0.001 |
WASO | 141 (12, 266) | 133 (32, 400) | 12 (2, 46) | 54.421 | <0.001 |
Sleep latency (minutes) | 20 (2, 207) | 17 (2, 74) | 13 (1, 94) | 3.915 | 0.169 |
Sleep efficiency (%) | 70.2 (17.4, 85.5) | 64.2 (34.4, 97.5) | 87.4 (54.3, 98.8) | 29.884 | <0.001 |
AHI | 7 (0, 73) | 5 (0, 45) | 4 (0, 11) | 34.842 | <0.001 |
Arousal index | 152 (1, 352) | 83 (2, 213) | 5 (0, 87) | 36.912 | <0.001 |
PLM index | 4 (0, 107) | 7 (0, 105) | 2 (0,12) | 13.443 | 0.002 |
Snore index | 0 (0, 3,779) | 1 (0, 2,534) | 0 (0, 0.0293) | 11.628 | 0.001 |
N1 duration (minutes) | 44 (15, 142) | 33 (20, 116) | 31 (2, 175) | 4.183 | 0.159 |
N1 percentage | 8 (3, 24) | 7 (4, 22) | 10 (0, 28) | 0.514 | 0.815 |
N2 duration (minutes) | 193 (57, 310) | 197 (61, 291) | 177 (0, 368) | 3.723 | 0.267 |
N2 percentage | 36 (13, 56) | 39 (11, 54) | 54 (12, 166) | 20.529 | <0.001 |
N3 duration (minutes) | 51 (0, 106) | 30 (0, 82) | 71 (0, 164) | 12.973 | 0.057 |
N3 percentage | 10 (0, 20) | 6 (0, 16) | 15 (0, 68) | 10.722 | 0.094 |
REM duration (minutes) | 53 (7, 149) | 53 (0, 120) | 66 (0, 177) | 0.311 | 0.928 |
REM percentage | 9 (1, 29) | 10 (0, 23) | 15 (0, 42) | 3.326 | 0.362 |
REM latency (minutes) | 138 (9, 358) | 116 (55, 445) | 81 (5, 281) | 14.598 | 0.024 |
Deep sleep latency (minutes) | 82 (19, 440) | 68 (28, 294) | 53 (7, 325) | 5.046 | 0.123 |
Sleep parameters of ET as a whole including ET and ET-Plus |
TETRAS total score |
FTMRS total score |
||
---|---|---|---|---|
Spearman’s rho | p value | Spearman’s rho | p value | |
AHI sleep | 0.589 | <0.001 | 0.573 | <0.001 |
Sleep period | -0.592 | <0.001 | 0.298 | 0.049 |
Wake duration | 0.348 | 0.022 | 0.439 | 0.003 |
Wake percentage | 0.336 | 0.028 | 0.448 | 0.003 |
WASO | -0.765 | <0.001 | 0.842 | <0.001 |
REM percentage | -0.419 | 0.005 | -0.195 | 0.206 |
REM latency (minute number) | 0.453 | 0.002 | 0.426 | 0.004 |
Sleep latency | 0.587 | <0.001 | 0.382 | 0.011 |
Sleep efficiency | -0.979 | <0.001 | -0.686 | <0.001 |
Stage N1 percentage | 0.227 | 0.139 | -0.241 | 0.115 |
Stage N2 percentage | -0.082 | 0.605 | -0.159 | 0.303 |
Stage N3 percentage | -0.366 | <0.001 | -0.105 | 0.499 |
Tremor characteristics of ET and ET-Plus. Values are presented as mean±standard deviation number (%), or median (interquartile range) unless otherwise indicated. indicates the use of ANOVA; the statistical test used is the Student t-test; the chi-square test was used for categorical variables; ET versus control; ET-Plus versus control; ET versus ET-Plus. ET, essential tremor; ET-Plus, essential tremor plus; BMI, body mass index; TETRAS, The Essential Tremor Rating Assessment Scale; ADL, activities of daily living; FTMRS, Fahn-Tolosa-Marin Clinical Rating Scale; PSQI, Pittsburgh Sleep Quality Index; ESS, Epworth Sleepiness Scale; RLS-Q, restless legs syndrome questionnaire; GAD-7, Generalized Anxiety Disorder Scale 7; PHQ-9, Patient Health Questionnaire-9; N/A, not applicable; ANOVA, analysis of variance.
ET versus control; ET-Plus versus control; ET versus ET-Plus. ET, essential tremor; ET-Plus, essential tremor plus; IQR, interquartile range; TIB, time in bed; WASO, wake after sleep onset; AHI, apnea‒hypopnea index; PLM, periodic limb movements; REM, reapid eye movement.
controlling for “age”. ET, essential tremor; ET-Plus, essential tremor plus; TETRAS, The Essential Tremor Rating Assessment Scale; FTMTRS, Fahn-Tolosa-Marin Clinical Rating Scale; AHI, apnea‒hypopnea index; WASO, wake after sleep onset; REM, reapid eye movement.