Storch et al.: Nonmotor fluctuations in Parkinson’s disease
Supplementary Material
Quantitative assessment of nonmotor fluctuations in
Parkinson’s disease using the Non Motor Symptoms Scale (NMSS)
Alexander Storch, M.D., Christine B. Schneider, M.D., Lisa Klingelhöfer, M.D., Per Odin, M.D., Ph.D, Gerd Fuchs, M.D., Wolfgang H. Jost, M.D., Pablo Martinez-Martin, M.D., Ph.D., Rainer Koch, M.D., Ph.D., Heinz Reichmann, M.D., Ph.D., K. Ray Chaudhuri, D.Sc., M.D., NoMoFlu-PD study group, Georg Ebersbach, M.D.
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Storch et al.: Nonmotor fluctuations in Parkinson’s disease
Supplementary Table S1. Demographic and clinical data
Overall cohorta / Patient cohort with complete NMSS datasets / Patient cohort with incomplete NMSS datasets / P valuebNo. of patients / 100 / 73 / 27
Men / Women / 54 (54%) / 46 (46%) / 39 (53%) / 34 (47%) / 15 (56%) / 12 (44%) / 1.000*
Age (years) / 68.49.7 (45-100) / 68.29.7 (46-100) / 68.99.9 (45-84) / 0.749§
Body mass index (kg/m2) / 25.8±4.9 (16.0-40.1) / 25.6±4.7 (16.0-39.6) / 26.3±5.5 (19.5-40.1) / 0.544§
Disease duration (years) / 11.3±6.2 (1-30) / 11.6±6.3 (1-30) / 10.3±5.8 (1-23) / 0.334§
Duration of motor complications (years) / 4.3±3.1 (1-30) / 4.4±3.2 (1-30) / 3.9±2.7 (2-10) / 0.506§
Hoehn & Yahr state
Hoehn & Yahr stage in On state / 2.7±0.9 (1.0-5) / 2.7±1.0 (1.0-4) / 2.8±0.8 (1.5-5) / 0.430$
Hoehn & Yahr stage in Off state / 3.40.9 (1.5-5) / 3.40.9 (1.5-5) / 3.10.9 (1.5-5) / 0.130$
PD treatment
Levodopa / 83 (89.2%) / 70 (95.9%) / 13 (65.0%) / 0.059*
Dopamine agonists / 63 (67.7%) / 52 (71.2%) / 11 (55.0%) / 0.110*
Amantadine / 22 (23.7%) / 16 (21.9%) / 6 (30.0%) / 0.553*
STN-DBS / 19 (19.0%) / 18 (25.0%) / 1 (5.0%) / 0.063*
Antidepressants / 21 (21.9%) / 19 (26.0%) / 2 (10.0%) / 0.225*
Antipsychotics / 23 (24.0%) / 2 (2.7%) / 1 (5.0%) / 0.521*
UPDRS score
UPDRS part I score / 2.9±2.4 (0-9) / 2.9±2.4 (0-9) / 2.6±2.3 (0-9) / 0.574§
UPDRS part II score / 14.5±6.8 (2-31) / 14.8±7.1 (2-31) / 13.5±5.9 (4-30) / 0.360§
UPDRS part III score in On state / 19.1±11.7 (2-70) / 18.4±12.0 (2-70) / 20.9±10.9 (6-56) / 0.343§
UPDRS part III score in Off state / 33.9±11.3 (10-61)# / 35.1±11.0 (15-61)# / 30.7±12.0 (10-57)# / 0.091§
ΔUPDRSIIIOn/Off / -16.6±9.6 (-43 to -1) / -16.7±13.4 (-43 to -1) / -9.8±7.8 (-27 to -1) / 0.053§
UPDRS part IV score / 7.2±3.5 (0-16) / 7.7±3.5 (2-16) / 5.9±3.1 (0-12) / 0.056§
Schwab & England ADL score in On state / 76.1±14.6 (20-100) / 75.4±12.7 (40-100) / 79.6±17.9 (20-100) / 0.053§
Schwab & England ADL score in On state / 54.621.2 (10-90)# / 51.019.6 (10-80)# / 65.920.6 (10-90)# / 0.141§
MMSE score / 28.01.6 (24-30) / 28.21.7 (24-30) / 27.72.2 (24-30) / 0.189§
PDQ-8 summary index / 26.1±12.9 (0-60) / 27.1±14.0 (0-60) / 23.1±9.3 (8-43) / 0.165§
BDI / 12.2±8.1 (0-44) / 12.3±8.1 (0-44) / 11.9±8.4 (0-37) / 0.796§
Data are mean (SD), median (range), or number (%).STN-DBS, deep brain stimulation of the subthalamic nucleus; UPDRS, Unified PD Rating Scale; ADL, Activities of daily living; MMSE, Mini-Mental-State Examination; PDQ-8, PD Questionnaire 8 items; BDI, Beck’s Depression Inventory.
P < 0.001 from Wilcoxon test; #P < 0.001 from paired two-sided t-test when compared to On state.
aDetails of demographic and clinical characteristics of the overall NoMoflu-PD study cohort are reported previously [1].
bP values are from *χ2 test or Fisher exact test (as appropriate); § unpaired two-sided t-test, or $ Jonckeere-Terpstra test.
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Storch et al.: Nonmotor fluctuations in Parkinson’s disease
Supplementary Table S2. Types of motor complications
Motor complication / No. of subjects (%)End-of dose akinesia / 60 (82%)
On-Off phenomenon / 62 (85%)
No On response / 34 (47%)
Off period dystonia / 52 (71%)
Peak-dose dyskinesia / 33 (45%)
Biphasic dyskinesia / 11 (15%)
Freezing / 56 (77%)
Data are numbers (%), multiple motor complication types per patient possible.
Supplementary Table S3. WOQ-9 resultsa
Symptom present / Improvement after the next dose of antiparkinsonian medicationaTremor / 45 (63%) / 32 (71%)
Slowness of movement / 69 (96%) / 55 (80%)
Mood changes / 41 (57%) / 22 (54%)
Any stiffness / 61 (85%) / 49 (80%)
Pain/aching / 48 (67%) / 26 (54%)
Reduced dexterity / 66 (92%) / 47 (71%)
Cloud mind / slowness of thinking / 45 (63%) / 32 (71%)
Anxiety/panic attacks / 22 (31%) / 14 (64%)
Muscle cramping / 38 (53%) / 24 (63%)
Data are numbers (%).
aPercentages are related to patients numbers experiencing the respective symptom.
Supplementary Table S4. Distribution of responses in NMS Questionnaire
Yes / No / UnknownDribbling / 31 (44%) / 40 (56%) / 2
Taste/smelling / 42 (58%) / 30 (42%) / 1
Dysphagia / 20 (28%) / 52 (72%) / 1
Vomiting / 12 (17%) / 60 (83%) / 1
Constipation / 40 (57%) / 30 (43%) / 3
Bowel incontinence / 3 (4%) / 67 (96%) / 3
Bowel emptying incomplete / 26 (37%) / 45 (63%) / 2
Urgency / 48 (67%) / 24 (33%) / 1
Nocturia / 57 (80%) / 14 (20%) / 2
Pain / 23 (32%) / 49 (68%) / 1
Weight / 17 (24%) / 55 (76%) / 1
Remembering / 31 (44%) / 40 (56%) / 2
Loss of interest / 27 (38%) / 45 (63%) / 1
Hallucination / 14 (20%) / 56 (80%) / 3
Concentrating / 41 (57%) / 31 (43%) / 1
Sad, blues / 38 (53%) / 34 (43%) / 1
Anxeity / 21 (30%) / 50 (70%) / 2
Sex drive / 16 (24%) / 52 (77%) / 5
Sex difficulty / 18 (27%) / 49 (73%) / 6
Dizzy / 31 (44%) / 39 (56%) / 3
Falling / 30 (42%) / 42 (58%) / 1
Daytime sleepiness / 23 (32%) / 49 (68%) / 1
Insomnia / 45 (64%) / 25 (36%) / 3
Intense vivid dreams / 29 (43%) / 39 (57%) / 5
Acting our during dreams / 34 (49%) / 36 (51%) / 3
Restless legs / 28 (42%) / 39 (58%) / 6
Swelling / 29 (40%) / 43 (60%) / 1
Sweating / 33 (46%) / 39 (54%) / 1
Diplopia / 14 (20%) / 56 (80%) / 3
Delusions / 6 (9%) / 65 (92%) / 2
Data are numbers (% of available data).
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Storch et al.: Nonmotor fluctuations in Parkinson’s disease
Supplementary Table S5. Reliability parameters of NMSS in On and Off state
Item/Domain / On state NMSS / Off state NMSSItem-total correlation (Cronbach’s α) / Inter-item correlation (range) / Floor / ceiling effects [%]a / Item-total correlation (Cronbach’s α) / Inter-item correlation (range) / Floor / ceiling effects [%]a
1. Light-headedness / 0.39 / 65% / 0% / 0.31 / 51% / 6%
2. Fainting / 0.39 / 90% / 0% / 0.31 / 90% / 0%
D1. Cardiovascular / (0.28) / 67% / 0% / (0.31) / 51% / 0%
3. Daytime sleepiness / 0.40 / 0.23-0.56 / 68% / 2% / 0.36 / 0.10-0.39 / 42% / 6%
4. Fatigue / 0.48 / 0.17-0.56 / 59% / 0% / 0.41 / 0.11-0.39 / 14%./ 8%
5. Difficulty falling asleep / 0.56 / 0.34-0.41 / 47% / 10% / 0.37 / 0.10-0.35 / 45% / 13%
6. Restless legs / 0.47 / 0.17-0.34 / 57% / 2% / 0.37 / 0.11-0.35 / 57% / 4%
D2. Sleep/Fatigue / (0.65) / 21% / 0% / (0.59) / 6% / 0%
7. Lost interests in surroundings / 0.77 / 0.43-0.79 / 80% / 0% / 0.76 / 0.35-0.67 / 41% / 4%
8. Lack motivation / 0.72 / 0.33-0.71 / 72% / 1% / 0.60 / 0.23-0.67 / 29% / 10%
9. Feel nervous / 0.44 / 0.33-0.46 / 72% / 0% / 0.30 / 0.09-0.54 / 45% / 2%
10. Seem sad / 0.75 / 0.46-0.73 / 61% / 1% / 0.58 / 0.37-0.54 / 31% / 6%
11. Flat mood / 0.71 / 0.34-0.78 / 68% / 1% / 0.59 / 0.04-0.70 / 38% / 4%
12. Difficulty experiencing pleasure / 0.87 / 0.34-0.78 / 68% / 2% / 0.52 / 0.04-0.70 / 34% / 6%
D3. Mood/Apathy / (0.88) / 38% / 0% / (0.80) / 10% / 1%
13. Hallucinations / 0.43 / 0.02-0.67 / 81% / 1% / 0.47 / 0.03-0.74 / 84% / 1%
14. Delusions / 0.57 / 0.10-0.67 / 85% / 1% / 0.58 / 0.09-0.74 / 83% / 1%
15. Double vision / 0.06 / 0.02-0.10 / 84% / 1% / 0.06 / 0.03-0.09 / 87% / 1%
D4. Perceptual problems /Hallucinations / (0.50) / 67% / 0% / (0.52) / 75% / 0%
16. Concentration / 0.82 / 0.76-0.84 / 73% / 3% / 0.59 / 0.52-0.62 / 41% / 11%
17. Forget things or events / 0.94 / 0.84-0.92 / 66% / 6% / 0.84 / 0.62-0.90 / 41% / 6%
18. Forget to do things / 0.88 / 0.76-0.92 / 69% / 6% / 0.76 / 0-52-0.90 / 60% / 6%
D5. Attention/Memory / (0.94) / 49% / 3% / (0.84) / 18% / 3%
19. Saliva / 0.27 / 0.18-0.38 / 66% / 0% / 0.33 / 0.12-0.34 / 56% / 6%
20. Swallowing / 0.25 / 0.08-0.38 / 86% / 0% / 0.18 / 0.12-0.18 / 78% / 0%
21. Constipation / 0.18 / 0.08-0.18 / 53% / 1% / 0.36 / 0.18-0.34 / 53% / 1%
D6. Gastrointestinal / (0.33) / 23% / 0% / (0.45) / 19% / 0%
22. Urgency / 0.76 / 0.61-0.78 / 69% / 4% / 0.62 / 0.53-0.57 / 53% / 7%
23. Frequency / 0.77 / 0.62-0.78 / 51% / 3% / 0.64 / 0.55-0.57 / 45% / 4%
24. Nocturia / 0.67 / 0.61-0.62 / 34% / 7% / 0.61 / 0.53-0.55 / 26% / 8%
D7. Urinary / (0.85) / 19% / 3% / (0.78) / 6% / 3%
25. Interest in sex / 0.16 / 85% / 0% / 0.48 / 69% / 7%
26. Problems having sex / 0.16 / 63% / 0% / 0.48 / 77% / 3%
D8. Sexual dysfunction / (0.23) / 63% / 0% / (0.62) / 60% / 1%
27. Pain / 0.34 / 0.15-0.33 / 67% / 3% / 0.12 / -0.07-0.23 / 53% / 4%
28. Taste or smell / 0.16 / -0.03-0.23 / 58% / 6% / 0.24 / 0.06-0.23 / 56% / 6%
29. Weight change / 0.36 / 0.15-0.33 / 81% / 0% / 0.28 / 0.08-0.25 / 80% / 0%
30. Excessive sweating / 0.13 / -0.03-0.15 / 71% / 1% / 0.06 / -0.07-0.25 / 62% / 6%
D9. Miscellaneous / (0.40) / 22% / 0% / (0.29) / 12% / 0%
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Storch et al.: Nonmotor fluctuations in Parkinson’s disease
Supplementary Table S6. Correlations of NMSS domains and items in On and Off state with UPDRS part III motor score
Domain/itema / Spearman’s ρUPDRS IIIOn / UPDRS IIIOff / ΔUPDRS IIIOn/Off
1. Light-headedness / 0.097 / -0.102 / 0.035
2. Fainting / 0.224* / 0.112 / -0.012
D1. Cardiovascular / 0.146 / -0.053 / 0.048
3. Daytime sleepiness / 0.162 / 0.124 / 0.101
4. Fatigue / 0.198* / 0.089 / 0.220*
5. Difficulty falling asleep / 0.176 / 0.141 / 0.161
6. Restless legs / 0.380** / 0.026 / 0.144
D2. Sleep/Fatigue / 0.294** / 0.172 / 0.263**
7. Lost interests in surroundings / 0.240* / 0.241* / 0.195
8. Lack motivation / 0.252* / 0.197* / 0.248*
9. Feel nervous / 0.279** / 0.046 / 0.005
10. Seem sad / 0.512** / 0.145 / 0.184
11. Flat mood / 0.451** / 0.361** / 0.216*
12. Difficulty experiencing pleasure / 0.386** / 0.278** / 0.202*
D3. Mood/Apathy / 0.540** / 0.289** / 0.284**
13. Hallucinations / 0.225* / 0.070 / 0.007
14. Delusions / 0.123 / -0.065 / 0.096
15. Double vision / 0.152 / 0.245* / 0.222*
D4. Perceptual problems /Hallucinations / 0.225* / 0.174 / 0.219*
16. Concentration / 0.280* / 0.169 / 0.262*
17. Forget things or events / 0.228 / 0.133 / 0.231
18. Forget to do things / 0.147 / 0.232* / 0.078
D5. Attention/Memory / 0.246* / 0.199 / 0.348**
19. Saliva / 0.260* / 0.109 / -0.136
20. Swallowing / 0.124 / -0.001 / 0.112
21. Constipation / 0.107 / 0.067 / -0.079
D6. Gastrointestinal / 0.210 / 0.173 / 0.069
22. Urgency / 0.279* / 0.212 / 0.019
23. Frequency / 0.238* / 0.116 / -0.136
24. Nocturia / 0.356** / 0.194 / -0.075
D7. Urinary / 0.299* / 0.246* / 0.101
25. Interest in sex / 0.216 / 0.100 / 0.162
26. Problems having sex / -0.007 / -0.064 / 0.158
D8. Sexual dysfunction / 0.132 / 0.042 / 0.186
27. Pain / 0.179 / 0.113 / 0.159
28. Taste or smell / 0.097 / 0.222 / -0.039
29. Weight change / 0.130 / 0.271* / 0.054
30. Excessive sweating / 0.145 / 0.046 / -0.043
D9. Miscellaneous / 0.225 / 0.277* / 0.210
NMSS total / 0.444** / 0.318** / 0.348**
*Represents significant correlations with P < 0.05, and ** with P < 0.01.
aScores with outcome variables in On and Off state, the difference, e.g. ΔNMSSOn/Off, is defined as On state values minus Off state values (more severe symptom in Off state leads to more negative results). Correlations of ΔNMSSOn/Off with these scores are calculated using the difference between On and Off state (Δscores).
UPDRS, Unified Parkinson’s Disease Rating Scale.
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Storch et al.: Nonmotor fluctuations in Parkinson’s disease
References
[1] Storch A, Schneider CB, Wolz M, Sturwald Y, Nebe A, Odin P, et al. Nonmotor fluctuations in Parkinson disease: Severity and correlation with motor complications. Neurology. 2013;80:800-9.
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