Movement Disorders

Vol. 25, No. 6, 2010, pp. 704–709

Ó 2010 Movement Disorder Society CME

The Nondeclaration of Nonmotor Symptoms of Parkinson’s

Disease to Health Care Professionals: An International Study
Using the Nonmotor Symptoms Questionnaire

K. Ray Chaudhuri, MD, DSc,1* Cristina Prieto-Jurcynska, MD,2,3 Yogini Naidu, MSc,4 Tanya Mitra, BSc,5
Belen Frades-Payo, MSc,6 Susanne Tluk, RGN,4 Anne Ruessmann, RGN,7 Per Odin, PhD,7 Graeme Macphee, MD,8
Fabrizio Stocchi, MD,9 William Ondo, MD,10 Kapil Sethi, MD, FRCP,11 Anthony H.V. Schapira, MD, DSc,12
Juan Carlos Martinez Castrillo, MD, PhD,13 and Pablo Martinez-Martin, MD, PhD6
1
National Parkinson Foundation Centre of Excellence, Kings College Hospital, Denmark Hill, London, United Kingdom
2
Alzheimer Disease Research Unit, Carlos III Institute of Health, Madrid, Spain
3
Department of Neurology, Infanta Elena Hospital (Valdemoro), Madrid, Spain
4
Department of Neurology, University Hospital Lewisham, London, United Kingdom
5
Department of Neuroscience, Guy’s, King’s and St. Thomas’ School of Medicine, London, United Kingdom
6
Alzheimer Disease Research Unit, National Center for Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain
7
Department of Neurology, Klinikum-Bremerhaven Reinkenheide, Bremerhaven, Germany
8
Department of Medicine for the Elderly, Southern General Hospital, Glasgow, United Kingdom
9
Department of Neurology, IRCCS San Raffaele, Rome, Italy
10
Department of Neurology, Baylor College of Medicine, Houston, Texas, USA
11
Department of Neurology, Medical College of Georgia, Athens, Georgia, USA
12
Department of Clinical Neurosciences, Institute of Neurology, Queen Square, UCL, London, United Kingdom
13
Department of Neurology, Ramon y Cajal University Hospital, Madrid, Spain

Abstract: The nonmotor symptoms (NMS) of Parkinson’s (delusions). The most frequently nondeclared symptoms
disease (PD) are less well recognised and can be more trou- were delusions, daytime sleepiness, intense and vivid
blesome to patients and carers than classical motor features. dreams, and dizziness. In many, appropriate treatments for
NMS are frequently missed during routine consultations and undeclared NMS were started only after these were recog-
such under-recognition may have implications on quality of nised following completion of NMSQuest. NMS of PD are
care given that many NMS are treatable. To determine the frequently undeclared at routine hospital consultation and
proportion of patients not declaring NMS to healthcare pro- may be related to the fact that patients often do not link
fessional (HCP) as assessed by self completion of the NMS these symptoms with PD or may be too embarrassed to dis-
questionnaire (NMSQuest), a validated, self-completing cuss these. Use of NMSQuest allows patients to flag symptoms
questionnaire with 30 items. Multicentre international study. which may be otherwise undeclared and remain untreated
The data was collected from PD patients across all age when potential treatments exist. Ó 2010 Movement Disorder
groups and stages attending outpatient clinics in specialist Society
and care of the elderly settings. 242 patients recruited and Key words: nonmotor symptoms; Parkinson’s disease;
undeclared NMS ranged from 31.8% (diplopia) to 65.2% nondeclared; NMSQuest; quality of life

Additional Supporting Information may be found in the online The nonmotor symptoms (NMS) of Parkinson’s dis-
version of this article. ease (PD) are a key cause of disability and contribute
*Correspondence to: K. Ray Chaudhuri, National Parkinson Foun-
dation Centre of Excellence, Kings College Hospital, Denmark Hill, to the deterioration of quality of life (QoL) in PD.
London, United Kingdom. E-mail: [email protected] Therefore, recognition of NMS is important for deliv-
Potential conflict of interest: Nothing to report. ery of modern and comprehensive healthcare for PD
Received 21 July 2009; Revised 10 September 2009; Accepted 6 patients.1,2 NMS of PD occur throughout the course ill-
October 2009
Published online 29 March 2010 in Wiley InterScience (www. ness from early to late disease. Although some NMS
interscience.wiley.com). DOI: 10.1002/mds.22868 of PD, such as, depression, dementia, dysautonomia,

704
 NONDECLARATION OF NMS OF PD TO HCP 705

and sleep problems, are well recognised, whereas clinic (University Hospital Lewisham) and care of the
others, such as, dribbling of saliva, weight changes, elderly movement disorders clinics (KCH and Sothern
sexual problems, and visual problems are less General Hospital, Glasgow) or research units (Alzhei-
known.1,3 Some NMS can be related to dopaminergic mer Disease Research Unit, Madrid, Spain). Routine
treatment, for example, dopamine dysregulation syn- demographic details and drug history were noted.
drome, drug-induced hallucinations or psychosis, and Where appropriate locally cross cultural validated
postural hypotension, whereas fluctuations in motor versions were used as used in the original NMSQuest
responses also may have major nonmotor components.1 validation and subsequent prevalence studies.
In spite of the importance of NMS, these symptoms After completion of NMSQuest (which relates to
are not well recognized in clinical practice. A study problems active in the past month), patients were
conducted in the US reported that existing depression, specifically asked if they had discussed the positive
anxiety, and fatigue are not identified by neurologists symptoms previously with any HCP and, if not, why.
in over 50% of consultations, and existing sleep dis- Declaration of NMS prompted appropriate review and
turbance in over 40%.4 Additionally, a UK Brain Bank management of individual symptoms in all patients.
based study reported that 21% of the sample as pre-
senting or premotor features, such as, pain, anxiety,
Data Analysis
and urinary dysfunction. These patients were more
likely to be misdiagnosed initially and received inap- Prevalence of each NMS was calculated by comput-
propriate medical interventions.5 The importance of ing the number of positive responses (symptoms) and
recognising NMS is underpinned by the fact that many calculation of percentage related to the number of
of NMS of PD, contrary to common perception are patients in the sample. For each item, the proportion of
treatable and may respond to dopaminergic therapy.6 nondeclared NMS was calculated based on the percent-
The NMSQuest is the first self completed 30 item age of patients declaring to suffer the symptom. For
screening tool containing nine NMS domains designed each NMSQuest domain, the number of declared
for rapid screening of NMS, empowering the patient symptoms (positive) and nondeclared symptoms was
and caregiver to flag up relevant NMS that may not be determined. Mann-Whitney and Kruskal-Wallis tests
otherwise discussed in consultations.7 Pilot validation were used for comparisons. The Spearman rank corre-
study assessing feasibility, validity, and acceptability lation coefficient was applied to determine associa-
of the NMSQuest has been published and the question- tions. Statistical analysis was carried out with Stata/IC
naire has been independently validated and recom- 10.1 (Stata Corp. LP, College station, TX).
mended for use in routine clinical practice by the
Department of Health in the UK as part of the 18-
week treatment pathway for PD.8,9 In this multicentre RESULTS
international study, we report observations from the A total of 242 patients, mean (6standard deviation)
use of NMSQuest across PD clinics and the percentage age 68.0 6 10.0 (range 34–91 years), male 63.2%,
of NMS declared on NMSQuest that may not have were examined. There were no significant differences
been previously discussed with the healthcare profes- among participant countries in relation to this charac-
sionals (HCP). teristic. Disease duration was 8.0 6 5.8 (range 1–28
years), with shorter disease duration in German
patients (6.4 6 5.9) and longer in Spanish patients
PATIENTS AND METHODS (8.9 6 5.5) (Kruskal-Wallis test, P 5 0.01). Twenty
PD patients (with the aid of caregivers when neces- two percent had tremor dominant PD, whereas 39.5%
sary) completed the NMSQuest (details of completion had akinesia dominant PD and 38.3% had mixed pat-
of NMSQuest has been described previously),7,8 tern of PD. The distribution of patients by HY stage is
whereas waiting to be seen by the HCP. Nondemented, shown in Table 1 and showed significant differences
consecutive PD patients of all ages and in all stages of by country (chi-squared, P 5 0.002).
the disease were included as long as they satisfied the The number and percentage of ‘‘positive’’ and ‘‘non-
UK PD brain bank criteria.10 Only patients with no declared’’ symptoms are shown in Table 2. The mean
previous experience of using NMSQuest were included of total NMSQuest positive symptoms was 10.9 6 5.6
to avoid potential bias in eliciting NMS patients were and the mean of undeclared symptoms was 4.6 6 4.1
recruited from both teaching hospital (KCH, London, (42.8% of the positive). Range of proportions for unde-
Bremerhaven, Germany), general hospital neurology clared NMS was from 31.8% (diplopia) to 65.2%

Movement Disorders, Vol. 25, No. 6, 2010

706 K.R. CHAUDHURI ET AL.

TABLE 1. HY stage and recruitment in the three countries There were not significant differences in the number
in current study of nondeclared NMS by sex. Only the domain
Hoehn and Yahr stage n Germany Spain United Kingdom depression/anxiety showed a marginal difference
(Mann-Whitney test, P 5 0.04), with more undeclared
1 22 7 8 7
2 121 5 62 54 symptoms for women (0.45 6 0.67) than for men
3 66 14 18 34 (0.29 6 0.57).
4 26 4 10 12 The number of undeclared NMS showed a low cor-
5 6 1 2 3
relation with age (rS 5 60.14; P 5 0.03), and further
N 5 241 (one missing). analysis suggest that patients aged 675 declared sig-
nificantly less NMS to the HCP than patients 675
years (5.0 6 4.1 vs. 3.8 6 4.0; Mann-Whitney test,
(delusions). Delusions, daytime sleepiness, intense and
P 5 0.01). NMS were present significantly more in
vivid dreams, and dizziness were the most frequently
akinesia dominant PD compared with the other sub-
nondeclared symptoms. In regard to the NMSQuest
types (Kruskal-Wallis test, P 5 0.008); however, there
dimensions/domains, the percentage of undeclared
was no difference in the percentage of undeclared
symptoms ranged from 36.8% (miscellaneous) to
NMS between the three subtypes of PD.
50.0% (hallucinations/delusions), Table 3.
When asked about why these were not declared the
Although mean positive NMSQuest scores did not
patients and caregivers responded by outlining the
differ significantly among the countries, mean unde-
following reasons:
clared NMS was significantly lower in Spanish patients
(3.2 6 3.0) compared with the German (5.5 6 3.7) a) They were not aware some of these symptoms may
and the UK patients (5.6 6 4.6) (Kruskall Wallis test, have been related to PD (delusions, RBD, intense and
P 5 0.0001). vivid dreams, pains, dribbling of saliva, insomnia),

TABLE 2. Number and percentage of positive and undeclared nonmotor symptoms

Positive Non-declared
Items N % n %*
1 Dribbling 101 41.7 46 45.5
2 Taste/smelling 103 42.9 41 39.8
3 Swallowing 65 27.0 24 36.9
4 Vomiting 38 15.8 16 42.1
5 Constipation 115 47.5 53 46.1
6 Bowel incontinence 15 6.3 5 33.3
7 Bowel emptying incomplete 65 27.0 31 47.7
8 Urgency 145 59.9 61 42.1
9 Nocturia 157 64.9 69 43.9
10 Pains 111 45.9 45 40.5
11 Weight 55 22.7 21 38.2
12 Remembering 124 51.2 55 44.4
13 Loss of interest 82 33.9 35 42.7
14 Hallucinations 41 17.0 17 41.5
15 Concentrating 121 50.0 46 38.0
16 Sad, blues 118 48.8 45 38.1
17 Anxiety 101 41.7 40 39.6
18 Sex_drive 90 37.3 41 45.6
19 Sex_difficulty 82 34.3 37 45.1
20 Dizzy 94 38.8 47 50.0
21 Falling 70 29.3 28 40.0
22 Daytime sleepiness 84 34.7 44 52.4
23 Insomnia 114 47.3 50 43.9
24 Intense, vivid dreams 84 34.7 44 52.4
25 Acting_out during dreams 93 38.7 41 44.1
26 Restless Legs 99 41.1 36 36.4
27 Swelling 91 37.6 33 36.3
28 Sweating 74 30.6 25 33.8
29 Diplopia 44 18.2 14 31.8
30 Delusions 23 9.5 15 65.2

*Frequency and percentage calculated on the number of positive responses.

Movement Disorders, Vol. 25, No. 6, 2010

 NONDECLARATION OF NMS OF PD TO HCP 707

TABLE 3. Declared (positive) and nondeclared symptoms us to use an instrument that empowers PD patients and
analysed according to NMSQuest domains carers to flag NMS in clinics.7 Only ‘‘NMSQuest na-
NMS Questionnaire—domains Positive Non-declared %* ive’’ patients were used for the study so that patients
were not previously exposed to NMSQuest. Answers
Gastrointestinal 2.1 6 1.6 0.9 6 1.1 43.5
Urinary 1.3 6 0.8 0.5 6 0.8 43.2 to NMSQuest related to problems active in the last
Sexual function 0.7 6 0.9 0.3 6 0.7 45.8 month and in all, therefore, undeclared symptoms
Cardiovascular 0.7 6 0.7 0.3 6 0.6 45.6 related to current active problems, which were not
Apathy/attention/memory 1.4 6 1.2 0.6 6 0.9 41.5
Hallucinations/delusions 0.3 6 0.6 0.1 6 0.4 50.0 flagged in their last consultation/meeting with a HCP.
Depression/anxiety 0.9 6 0.8 0.4 6 0.6 38.9 The spread of the clinics allowed assessment of
Sleep disorder 2.0 6 1.5 0.9 6 1.2 45.2 patients in specialised to general neurology clinics to
Miscellaneous 1.6 6 1.1 0.6 6 0.8 36.8
reduce potential bias. Patients with disease severity
Mean 6 standard deviation. rated from mild PD to severe PD based on Hoehn and
*Percentage calculated on the number of positive responses.
Yahr staging were included as long as they were able
to complete NMSQuest in a satisfactory fashion. How-
ever, as is reflected in many observational studies, the
b) They were embarrassed to discuss these issues with proportion of stage 5 PD (HY stage) was low.
the HCP unless they were prompted (sexual prob- In line with previous observation reported in the
lems, incontinence of bowel), international NMS prevalence study,8 we observed that
c) The consultation time was mostly preoccupied by the mean NMS reported on use of NMSQuest was
discussion on motor symptomatology and as such around 10. In contrast, the mean of ‘‘undeclared’’ NMS
no or little time was available for discussion of any was 4.65 6 4.07 (42.8% of the positive) indicating
NMS related issues. that on average there are four undeclared NMS per
patient. The range of undeclared NMS was wide with
These answers were obtained as complementary infor- delusions, daytime sleepiness, intense and vivid
mation, but were not tabulated for quantitative analysis. dreams, and dizziness being the most undeclared,
whereas potentially treatable NMS, such as, dribbling
of saliva, low mood, insomnia, REM behaviour disor-
der, restless legs syndrome type symptoms, and falls
DISCUSSION
were also often undeclared (Table 2). When analysed
This international study reports some key observa- by NMSQuest domains (Table 3), there was a more
tions in the ‘‘routine’’ clinical care of patients with PD. even spread of nondeclared symptoms grouped by
These are: domains ranging from 36.7% (miscellaneous including
a) A range of NMS of PD are often undeclared to pain, weight change) to 50% (hallucinations, delu-
HCP unless a specific tool, such as, the NMSQuest sions).
is used. A key issue that emerges from this study is that
b) The ‘‘nondeclaration’’ of NMS occurs across several many of the undeclared NMS are treatable. These
countries in Europe irrespective of the setting status include targeted dopaminergic or nondopaminergic
(teaching hospital, general neurology clinic, research therapy for depression, low mood, insomnia, EDS,
unit) and, therefore, is likely to be translated as a RBD, RLS dribbling of a saliva, pains, anxiety to men-
whole to PD patients attending hospital clinics. tion a few.6 It is well recognised that NMS, such as,
c) The undeclared symptoms include several poten- depression, EDS, falls are key determinants of health
tially treatable NMS, such as, EDS, low mood, drib- related QoL in PD.11–14 It is, therefore, reasonable to
bling of saliva, insomnia, RBD, RLS, and following speculate that in our patient group, undeclared NMS
this study, appropriate referrals and treatments were has the potential to adversely affect QoL as it is likely
started in several cases. that without the use of an empowering tool, such as,
d) Relatively younger patients declare NMS less fre- the NMSQuest such symptoms would not have been
quently compared with older (675 years) patients. addressed.
The range of undeclared NMS items was 33.2% (di-
We included a reasonable ‘‘real life’’ patient popula- plopia) to 65.2% (delusions). During the study, the fol-
tion, across all age groups to address the issue of lowing undeclared NMS were specifically addressed in
‘‘nondeclaration’’ of NMS in outpatient clinics. The terms of management and treatment with successful
validated and internationally used NMSQuest allowed outcomes as follows:

Movement Disorders, Vol. 25, No. 6, 2010

708 K.R. CHAUDHURI ET AL.

Dribbling of saliva (45.5% undeclared) and swallow- Acknowledgments: This work was supported by the
ing difficulty (36.9% undeclared): referral to speech National Parkinson Foundation (US) and International PD
Nonmotor Group.
and language therapy and nutritional advice,
Urinary urgency (42.1% undeclared): referral to Financial Disclosures: (for the past year): K. Ray
Chaudhuri: Consultant: GSK, BI, Britannia, Solvay; Grants/
urologist for bladder care, Research Support: GSK, BI, UCB, Solvay; Honoraria: GSK,
REM behaviour disorder (RBD, 44.1% undeclared): BI, Solvay, UCB; Intellectual Property Rights: None; Owner-
further confirmation was sought and referral for pol- ship Interest: None; Royalty: None; Other: None; P. MartÚ-
ysomnography was made in appropriate cases, nez-MartÚn: None. F. Stocchi: Consultant: Novartis, GSK,
whereas others received treatment with clonazepam Pfizer, Teva, Vernalis, Valeant, BI, KV; Grants/Research
Support: Novartis, Valeant, GSK; Honoraria: Novartis, GSK,
or melatonin. Pfizer, Valeant; Intellectual Property Rights: None; Owner-
ship Interest: None; Royalty: None; Other: None. P. Odin:
Daytime sleepiness (52.4% undeclared), constipation Consultant: BI, Solvay, UCB; Grants/Research Support:
(46.1% undeclared), unexplained pains (40.5% unde- None; Honoraria: BI, Cephalon, GSK, Solvay, Orion; Intel-
clared), sadness and blues (38.1% undeclared), restless lectual Property Rights: None; Ownership Interest: None;
Royalty: None; Other: None. G. Macphee: Consultant: BI,
legs type symptoms (36.4% undeclared), and insomnia GSK, Teva, Solvay; Grants/Research Support: BI, UCB
(43.9% undeclared) were treated as appropriate with Travel grants; Honoraria: BI, Orion, GSK, Solvay;
medications with satisfactory outcomes. In addition, Intellectual Property Rights: None; Ownership Interest: None;
patients that were assessed in the research unit were Royalty: None; Other: None. Y. Naidu, T. Mitra, C.
advised to visit their doctors for discussing the results Prieto-Jurcynska, B. Frades-Payo, A. Ruessmann, S. Tluk:
None.
with the NMSQuest.
No relationship with undeclared NMS and sex of the Author Roles: K.R. Chaudhuri, P. Martinez-Martin, P.
Odin, G. Macpheeconceived the study and took part in plan-
patient was observed. Although, akinesia dominant PD ning, protocol finalisation, collecting data, and writing paper.
reported a greater number of NMS, there was no dif- K. Sethi, A.H.V. Schapira, F. Stocchi, W. Ondomembers of
ference in undeclared NMS between the three clinical the PD nonmotor group, reviewed paper, collected data, and
subtypes of PD. Surprisingly, we found older patients provided input to manuscript. C. Prieto-Jurcynska, B. Frades-
declared NMS more frequently than younger patients. Payo, Y. Naidu, S. Tluk, A. Ruessmann, T. Mitralocal coor-
dinators collecting data, interviewing patients, creating data-
We are unable to explain this observation apart from base, and assisting writing.
the fact that questions on NMS are generally more
likely to be asked in older patient consultations and
younger patients may not be too forthcoming in declar- REFERENCES
ing some NMS, which may be perceived as socially 1. Chaudhuri KR, Healy D, Schapira AHV. The non motor symp-
embarrassing. The rate of undeclared NMS was signifi- toms of Parkinson’s disease. Diagnosis and management. Lancet
Neurol 2006;5:235–245.
cantly lower in the Spanish centre. This may reflect a 2. Aarsland D, Larsen JP, Goek Lim N, et al. Range of neuro-
better understanding of NMS and longer consultation psychiatric disturbances in patients with Parkinson’s disease.
times allowed in these clinics. J Neurol Neurosurg Psychiatry 1999;67:492–496.
3. Naidu Y, Chaudhuri KR. Early Parkinson’s disease and non
Akinesia dominant PD patients reported more NMS motor issues. J Neurol 2008;255 (Suppl 5):33–38.
than tremor dominant subtype (Table 3), however, 4. Shulman LM, Taback RL, Rabinstein AA, Weiner WJ. Non-
all three subtypes has similar rates of undeclared recognition of depression and other non-motor symptoms in
Parkinson’s disease. Parkinsonism Relat Disord 2002;8:193–
NMS. 197.
In conclusion, this study indicates that NMS in PD 5. O’sullivan SS, Williams DR, Gallagher DA, et al. Non motor
continues to be poorly detected in wider clinical prac- symptoms as presenting complaints in Parkinson’s disease: a
clinicopathological study. Mov Disord 2008;23:101–106.
tice. Part of this is related to nondeclaration of NMS 6. Chaudhuri KR, Schapira AHV. The non motor symptoms of Par-
by patients, on average four NMS per patient. Unless kinson’s disease: dopaminergic pathophysiology and treatment.
prompted by a simple self completing instrument, such Lancet Neurol 2009;8:464–474.
7. Chaudhuri KR, Martinez-Martin P, Schapira AHV, et al. An
as, the NMSQuest, many such symptoms may not be international multicentre pilot study of the first comprehensive
declared leading to a potentially suboptimal patient self-completed non-motor symptoms questionnaire for Parkin-
care, increased cost of care14 and compromised QoL. son’s disease: the NMSQuest study. Mov Disord 2006;21:916–
923.
This has been translated to routine clinical practice in 8. Martinez-Martin P, Schapira AHV, Stocchi F, et al. Prevalence
the UK, where the government department of health of non motor symptoms in Parkinson’s disease in an international
has recommended NMSQuest to be routinely used in setting; study using non-motor symptoms questionnaire in 545
patients. Mov Disord 2007;22:1623–1629.
the ‘‘18 week pathway’’ for treatment and management 9. National Health Service, Department of Health. UK. The 18
of PD. week commissioning pathway for treatment and management of

Movement Disorders, Vol. 25, No. 6, 2010

 NONDECLARATION OF NMS OF PD TO HCP 709

tremor disorders. Available at: www.18weeks.nhs.uk. Neurology, 12. Schrag A, Jahanshahi M, Quinn N. What contributes to quality
Tremor Pathway. Accessed on 29 August, 2009. of life in patients with Parkinson’s disease? J Neurol Neurosurg
10. Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical Psychiatry 2000;69:308–312.
diagnosis of idiopathic Parkinson’s disease: a clinico-pathological 13. Martinez-Martin P, Serrano-Duenas M, Forjas MJ, Serrano
study of 100 cases. J Neurol Neurosurg Psychiatry 1992;55:181– MS. Two questionnaires for Parkinson’s disease: are the
184. PDQ- 39 and PDQL equivalent? Qual Life Res 2007;16:
11. Global Parkinson,’s Disease Survey Steering Committee. Fac- 1221–1230.
tors impacting on quality of life in Parkinson’s disease: 14. Findley L, Aujla M, Bain PG, et al. Direct economic impact of
results from an international survey. Mov Disord 2002;17:60– Parkinson’s disease: a research survey in the United Kingdom.
67. Mov Disord 2003;18:1139–1145.

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