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Parkinson's Disease
Volume 2011 (2011), Article ID 292719, 13 pages
http://dx.doi.org/10.4061/2011/292719
Research Article

Development of a Non-Motor Fluctuation Assessment Instrument for Parkinson Disease

1Baycrest Hospital, University of Toronto, 3560 Bathurst Street, Toronto, ON, Canada M6A 2E1
2Parkinson's Disease Research Education and Clinical Center (PADRECC), Philadelphia VA Medical Center, Philadelphia, PA 19107, USA
3Toronto Western Hospital, University of Toronto, Toronto, ON, Canada M5I 2S8
4School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

Received 25 April 2011; Accepted 24 May 2011

Academic Editor: Alan R. Crossman

Copyright © 2011 Galit Kleiner-Fisman et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Patients with Parkinson disease are increasingly recognized to suffer from non-motor symptoms in addition to motor symptoms. Many non-motor symptoms fluctuate in parallel with motor symptoms and in relationship to plasma levodopa levels. Though these symptoms are troublesome and result in reduced quality of life to patients and their caregivers, there has not been an objective method of recognizing and quantifying non-motor fluctuations (NMFs). This study sought to develop a patient-based instrument that would accurately capture the experience of patients with NMFs. Patient-based nominal group technique sessions, focus groups, and expert opinion were utilized in developing this questionnaire.

1. Introduction

Non-motor symptoms in Parkinson Disease (PD) are increasingly recognized as a major source of disability for patients with moderate to advanced PD. Disability due to these symptoms arises as a result of problems with, among other difficulties, sleep, cognitive and mood disturbances, pain and other sensory complaints, as well as bowel and bladder dysfunction [1, 2]. Many are poorly responsive to dopaminergic drug replacement given their partial mediation through other (nondopaminergic) neurotransmitter systems [3].

Non-motor fluctuations (NMFs), in contrast, are non-motor symptoms that vary according to plasma dopaminergic tone in a manner similar to motor fluctuations [4]. While it is likely that these NMFs are highly amenable to medical (dopamine replacement) and surgical interventions, there has been no instrument available to assess presence of NMFs, and this has limited the assessment of symptomatic burden and, therefore, efforts to pursue interventions. Even if such interventions were readily available, however, the lack of a reliable and valid instrument to assess the presence of NMFs would limit measurement of efficacy in clinical trials. As such, the objective of this study was to develop an instrument that assesses the presence of NMFs in individuals with PD and does so with reliability and validity.

2. Methods

2.1. Participants

As individuals with motor fluctuations are thought to be at greater risk for NMFs, individuals with motor fluctuations were recruited by (i) mailing pamphlets about the study and its eligibility criteria to all the Parkinson's Disease Research, Education & Clinical Center (PADRECC) patients at the Philadelphia VA Medical Center (PVAMC), (ii) distributing similar pamphlets at PD patient and caregiver support groups, and at the Pennsylvania Hospital Movement Disorders Center reception area, and by (iii) direct questioning of patients during a routine health care visit if they were listed as having symptoms of NMFs in the PADRECC electronic database. A screening questionnaire was administered to those with motor fluctuations who expressed interest in study participation to verify the presence of motor fluctuations and to assess level of awareness and knowledge about non-motor symptoms. Anyone with substantial cognitive impairment, defined as a Mini-Mental Status Exam (MMSE) score ≤24 (whereby scores had been obtained by any health care provider in the previous six months), was excluded [5].

The study was approved by the Institutional Review Boards (IRB) of the PVAMC and the Pennsylvania Hospital. All participants signed the IRB-approved, written informed consent form before participation.

2.2. Group Discussion Using Nominal Group Technique

Three group discussions were held to generate content for the questionnaire. Three to four unique patient and partner/caregiver dyads were recruited for each session (Figure 1). Nominal Group Technique (NGT) was employed [6]. Each NGT group began with the group facilitator (G.K-F.) reading from a semistructured interview script that operationally defined NMFs (symptoms related to PD that affect functions of the body other than movements, that come and go throughout the day depending on medication response).

292719.fig.001
Figure 1: NMF questionnaire development schema. NGT: nominal group technique. *Focus group consisted of both new subjects and original members of the NGT sessions.

Participants were asked to identify and record on paper all NMFs affecting them with particular attention paid to those NMFs that affected day-to-day life and/or life quality. Participants then took turns presenting their written responses such that with each cycle around the table the participant offered a single response. Every response offered by a group member was discussed by the whole group until all participants understood the NMF symptom offered and reached consensus on the language best describing that symptom. Precipitating and aggravating factors for each NMF symptom was discussed as was whether it was correlated with a particular motor state (e.g., ON versus OFF).

“Round-robins” continued until all unique responses were exhausted, after which a (secret ballot) vote took place to determine which symptoms were most frequent and disabling. A final composite list for each session was compiled before the group discussion ended and the group reviewed the findings. Group discussions not only identified content for instrument construction using lay language, they also applied meaning to the content and provided a sense of its relative perceived importance.

The complete list of all candidate symptoms identified by patient and caregivers were subjected to further critique by clinicians with expertise in PD. The clinicians were selected from the panel on non-motor symptoms of PD of the Quality Standards Subcommittee of the American Academy of Neurology [7]. Critique focused on frequency of and disability incurred by each symptom with the intention of reducing the number of total items to limit the burden of completing a lengthy questionnaire. Clinician experts’ critique led to creation of an initial questionnaire. In constructing this initial questionnaire, a 7th grade reading level was sought.

2.3. Focus Groups

The initial questionnaire was presented to two focus groups that consisted both of previous participants from NGT sessions and new patients. Participants were asked to critique the questionnaire for item relevance and ease of understanding, and whether response choices were both exhaustive and mutually exclusive. Important gaps in content were identified along with suggestions for questions that should be included to capture the content. Unnecessary or duplicative questions also were identified and removed. Following this process, a revised questionnaire was distributed to clinician experts for a final review.

2.4. Final Questionnaire

An additional goal of the final questionnaire was to create response options that would allow differentiation between non-motor symptoms that were present but did not fluctuate according to plasma dopaminergic tone, and those that did fluctuate. A scoring scheme was developed that consisted of imputing one to three points (mild, moderate, severe) for each endorsed item that indicated a symptom that fluctuated by “ON” versus “OFF” status, and 0 for all other options. As such, higher scores would reflect a greater number and severity of NMFs. A total NMF score ranges from 0 to 84, and subscores (mood/cognition, autonomic, sensory, sleep, and fatigue) could be generated in the “ON” and “OFF” periods.

3. Results

3.1. Patients

Baseline characteristics of patient-participants are detailed in Table 1. A total of 11 patients and 11 caregivers participated in NGT and focus groups. All patient participants had motor and non-motor fluctuations. Patient-participants were male with the exception of one woman (the majority of patient-participants were recruited from the male-predominant VA-based PADRECC).

tab1
Table 1: Characteristics of patient-participants.
3.2. Initial Questionnaire

Table 2 is a list of 33 symptoms that was constructed using all symptoms reported during the three sessions. These were then ranked from highest to lowest according to a “summary score” that was calculated by multiplying the number of participants who had reported the symptom by the mean rank of importance that had been reported by participants for that symptom. Symptoms reported by participants but not ranked as important were included in the table.

tab2
Table 2: Ranking of non-motor fluctuations (NMFs) symptoms by study participants*.

Clinician experts collapsed some items they believed to be assessing the same underlying concept into one single item (e.g., decreased reading comprehension and poor concentration and decreased communication and word-finding difficulties) and removed other items they thought were not highly prevalent in clinical practice (e.g., altered hearing). In those situations where multiple same-construct symptoms were collapsed into a single item, wording was revised to capture the concept appropriately.

The final revised questionnaire resulting from focus groups with patient/caregiver/ and feedback from clinician experts is shown in the appendix. Twenty-eight items were included in the final questionnaire.

4. Discussion

Outcome assessments based on patient perceptions and self-reports are increasingly incorporated into clinical trials of patients with PD. No instrument existed previously to allow assessment of NMFs in patients with PD. This study has led to the creation of such an instrument, the Non-motor Fluctuations Assessment instrument (NoMoFA), which can be used as a patient-based outcome measure in both research and clinical practice. While this instrument was developed using methods that impart substantial face and construct validity, reliability and additional validity assessments of the instrument necessarily must follow. To that end, a recent effort to identify wearing off phenomena both motor and non-motor, determined through expert consensus and literature review, identified similar symptoms to our patient-derived items [8].

Though patients have long complained of non-motor symptoms to their health-care providers, only recently have they been recognized as important and disabling [9]. Even amongst Movement Disorder specialists, attention to these problems has been limited [10]. Unfortunately, there is a discrepancy between the prevalence of NMFs and the limited degree to which these symptoms are attended to by health care professionals. However, studies indicate that NMFs are common and contribute significantly to reduction in quality of life. As shown by Witjas et al., up to one-third of patients reported greater disability from NMFs than from motor symptoms [9].

Due to the recent increased attention given to NMFs, a new effort has sought to incorporate evaluation of non-motor symptoms into the standardized PD evaluation protocol [8, 11, 12]. The questionnaire reported here will increase the likelihood that such a standardized evaluation will occur and will do so using an instrument with patient-derived content and with use of vocabulary obtained from patients themselves.

5. Conclusion

In developing the NoMoFA, we sampled a heterogeneous group of patients with diverse backgrounds. In addition, we received feedback from experts providing revisions with an effort to maximize clinical relevance. We believe this has increased the likelihood the NoMoFA is an accurate, understandable, comprehensive compilation of NMFs experienced by PD patients. Further work needs to be performed to ensure that the NoMoFA is reliable and valid before it can be incorporated into standard research and clinical evaluations of patients.

Appendix

Non-Motor Fluctuation Assessment Instrument (NoMoFA)

Many people with Parkinson disease have symptoms related to their muscles (movement symptoms). These include stiffness, slowness in carrying out movements, and trouble with walking, getting up from a chair, or using their hands. However, people living with Parkinson disease can also have symptoms that are not related to their movement (nonmovement symptoms). These nonmovement symptoms include things like problems in thinking and memory, pain, abnormal body sensations, difficulty with emptying bowels or troubles with the bladder. Many people do not know that these other symptoms (nonmovement symptoms) may be related to Parkinson disease or to how their body responds to medications taken for Parkinson disease (levodopa, prolopa, Sinemet).

For people experiencing nonmovement symptoms that change in response to Parkinson disease medications, symptoms may only occur or may get worse when medications are either working or not working.

This questionnaire only asks about the nonmovement symptoms that come and go in response to effects of Parkinson disease medications.

For each question, if the symptom was present in the past week, you will be asked to rate how bothersome it was for you. The choices of answers are mild, moderate, or severe.

Mild
The symptom did not affect my ability to carry out normal daily tasks or social activities

Moderate
The symptom affected but did not prevent me from carrying out normal daily tasks or social activities

Severe
Symptom prevented me from carrying out normal daily tasks or social activities.

NoMoFA
Investigator:
Subject ID:
Date Performed:
          Day       Month   Year

(1)In the last week, did you lose your train of thought?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNo Answer ONE of the following only if you answered “yes” to above: Was losing your train of thought related to when your levodopa WAS working? Please rate the severity.Mild ModerateSevere ORWas losing your train of thought related to when your levodopa WAS  NOT working? Please rate the severity.Mild ModerateSevere(2)In the last week, did you get distracted from completing a task?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was getting distracted related to when your levodopa WAS working?Please rate the severity.MildModerateSevereORWas getting distracted related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(3)In the last week, did you have difficulty planning or carrying out an activity (e.g., planning a party, making a grocery list, planning a menu, etc.)?YesNo If you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was difficulty planning or carrying out an activity related to when your levodopa WAS working? Please rate the severity.MildModerateSevereORWas difficulty planning or carrying out an activity related to when your levodopa WAS  NOT working? Please rate the severity.MildModerateSevere(4)In the last week, were you disoriented (such that you did not know what day it was, or where you were, or what you were doing)?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was disorientation related to when your levodopa WAS working? Please rate the severity.MildModerateSevereORWas disorientation related to when your levodopa WAS  NOT working? Please rate the severity.MildModerateSevere(5)In the last week, were you confused such that you had difficulty performing simple tasks (e.g., prepare a cup of tea, make a phone call)?YesNo If you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was confusion related to when your levodopa WAS working?Please rate the severity.MildModerateSevereORWas confusion related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(6)In the last week, did you have difficulty finding the right words when speaking?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was difficulty finding the right words related to when your levodopa WAS working?Please rate the severity.MildModerateSevereORWas difficulty finding the right words related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(7)In the last week, were you excessively worried?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was feeling excessively worried related to when your levodopa WAS working?Please rate the severity. MildModerateSevereORWas feeling excessively worried related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(8)In the last week, did you feelscared or threatened?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was feelingscared or threatened related to when your levodopa WAS working?Please rate the severity. MildModerateSevereORWas feelingscared or threatened related to when your levodopa WAS  NOT working?Please rate the severity. MildModerateSevere(9)In the last week, did you feelrestless?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was feelingrestless related to when your levodopa WAS working?Please rate the severity. MildModerateSevereORWas feelingrestless related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(10)In the last week, did you feelsad or hopeless?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was feelingsad or hopeless related to when your levodopa WAS working?Please rate the severity.MildModerateSevereORWas feelingsad or hopeless related to when your levodopa WAS  NOT working?Please rate the severity. MildModerateSevere(11)In the last week, were you more likely to feelalone?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was feelingisolated related to when your levodopa WAS working?Please rate the severity. MildModerateSevereORWas feelingisolated related to when your levodopa WAS  NOT working?Please rate the severity. MildModerateSevere(12)In the last week, did you see things or people that were not there?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoWas seeing things or people that were not there related to when your levodopa WAS working?Please rate the severity.MildModerateSevereORWas seeing things or people that were not there related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(13)In the last week, did you make poor decisions?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was making poor decisions related to when your levodopa WAS working?Please rate the severity.MildModerateSevereORWas making poor decisions related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(14)In the last week, were you more likely to act quickly without thinking things through?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was acting without thinking things through related to when your levodopa WAS working?Please rate the severity.MildModerateSevereORWas acting without thinking things through related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(15)In the last week, were you more likely to have a strong uncontrollable urge to do things (like gamble, eat too much, spend too much money or have more frequent thoughts about sexual activity)?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was having a strong uncontrollable urge to do things related to when your levodopa WAS working?Please rate the severity.MildModerateSevereORWas having a strong uncontrollable urge to do things related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(16)In the last week, did you have poor short-term memory (like putting things down and forgetting where you put them)?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was poor short-term memory related to when your levodopa WAS working?Please rate the severity.MildModerateSevereORWas poor short-term memory related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(17)In the last week, did you have difficulty handling stressful situations or feel overwhelmed in stressful situations?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was difficulty handling stressful situations related to when your levodopa WAS working?Please rate the severity.MildModerateSevereORWas difficulty handling stressful situations related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(18)In the last week, did you lose interest in activities that you previously enjoyed?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was losing interest in activities that you previously enjoyed related to when your levodopa WAS working?Please rate the severity.MildModerateSevereOR

Was losing interest in activities that you previously enjoyed related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(19)In the last week, did you feel sluggish or have low energy levels?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was feeling sluggish or having low energylevels related to when your levodopa WAS working?Please rate the severity.MildModerateSevereOR

Was feeling sluggish or having low energylevels related to when your levodopa WAS  NOT working? Please rate the severity.MildModerateSevere(20)In the last week, did you feel excessively sleepy during the day?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was feeling excessively sleepy during the day related to when your levodopa WAS working?Please rate the severity.MildModerateSevereORWas feeling excessively sleepy during the day related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(21)In the last week, did you have painful sensations in your body (e.g., aching, tightness, burning, or sharp, dull or throbbing pain)?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was having painful sensations in your body related to when your levodopa WAS working?Please rate the severity.MildModerateSevereORWas having painful sensations in your body related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(22)In the last week, did you have strange sensations in your bodyYesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was having strange sensations in your body related to when your levodopa WAS working?Please rate the severity.MildModerateSevereORWas having strange sensations in your body related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(23)In the last week, did you feel short of breath?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was feeling short of breath related to when your levodopa WAS working?Please rate the severity.MildModerateSevereORWas feeling short of breath related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(24)In the last week, did you have problems with vision (such as seeing double or things appearing blurry)?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Were problems with vision related to when your levodopa WAS working?Please rate the severity.MildModerateSevereORWere problems with vision related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(25)In the last week, did you have an increase in sweating (such that your clothes were damp or stained from sweat more than in the past)?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?Answer ONE of the following only if you answered “yes” to above:Was the change in sweating related to when your levodopa WAS working?Please rate the severity.MildModerateSevereORWas the change in sweating related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(26)In the last week, did you feel that your heart was racing, had skipped a beat, or was pounding?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Were heart racing, skipping a beat, or pounding related to when your levodopa WAS working?Please rate the severity.MildModerateSevereORWere heart racing, skipping a beat, or pounding related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(27)In the last week, did you urinate more frequently or had to get to the bathroom urgently?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Were urinating more frequently or having to get to the bathroom urgently related to when your levodopa WAS working?Please rate the severity.MildModerateSevereORWere urinating more frequently or having to get to the bathroom urgently related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere(28)In the last week, did you have difficulty having a bowel movement?YesNoIf you answered “yes”, did this get better or worse after you took your levodopa?YesNoAnswer ONE of the following only if you answered “yes” to above:Was difficulty having a bowel movement related to when your levodopa WAS working?Please rate the severity.MildModerateSevereORWas difficulty having a bowel movement related to when your levodopa WAS  NOT working?Please rate the severity.MildModerateSevere

Do you have any other nonmovement symptoms that come and go depending on when you took your Parkinson medications that you feel are important and that were NOT mentioned in this questionnaire? If so, please describe:

Please only respond to this section if this is the SECOND  TIME responding to the questionnaire:Today, are your PD movement symptoms better, worse, or the same as when you answered the first questionnaire?Today, are your PD nonmovement symptoms better, worse, or the same as when you answered the first questionnaire?Are you taking the same PD medication today compared to last week? If not, please list the changes.

Acknowledgments

The authors thank Dr. A. Siderowf for facilitation of data acquisition at Pennsylvania Hospital. They also wish to thank the clinician expert panel members: Drs. Anderson, Miyasaki, Samuel, Siderowf, Shulman, Stacy, Voon, and Weiner. This study was supported by a competitive pilot project grant from the Philadelphia VA Medical Center.

References

  1. K. R. Chaudhuri, D. G. Healy, and A. H. V. Schapira, “Non-motor symptoms of Parkinson's disease: diagnosis and management,” The Lancet Neurology, vol. 5, no. 3, pp. 235–245, 2006. View at Publisher · View at Google Scholar · View at Scopus
  2. K. R. Chaudhuri, L. Yates, and P. Martinez-Martin, “The non-motor symptom complex of Parkinson's disease: a comprehensive assessment is essential,” Current Neurology and Neuroscience Reports, vol. 5, no. 4, pp. 275–283, 2005. View at Scopus
  3. O. Hornykiewicz, “Biochemical aspects of Parkinson's disease,” Neurology, vol. 51, no. 2a supplement 2, pp. S2–S9, 1998. View at Scopus
  4. K. Widnell, “Pathophysiology of motor fluctuations in Parkinson's disease,” Movement Disorders, vol. 20, supplement 11, pp. S17–S22, 2005. View at Publisher · View at Google Scholar · View at Scopus
  5. W. A. Kukull, E. B. Larson, L. Teri, J. Bowen, W. McCormick, and M. L. Pfanschmidt, “The mini-mental state examination score and the clinical diagnosis of dementia,” Journal of Clinical Epidemiology, vol. 47, no. 9, pp. 1061–1067, 1994. View at Publisher · View at Google Scholar · View at Scopus
  6. C. Moore, Nominal Group Technique in Group Techniques for Idea Building, Applied Social Research Methods Series, Sage, Thousand Oaks, Calif, USA, 2nd edition, 1994.
  7. J. M. Miyasaki, K. Shannon, V. Voon et al., “Practice parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology,” Neurology, vol. 66, no. 7, pp. 996–1002, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Stacy and R. Hauser, “Development of a patient questionnaire to facilitate recognition of motor and non-motor wearing-off in Parkinson's disease,” Journal of Neural Transmission, vol. 114, no. 2, pp. 211–217, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. T. Witjas, E. Kaphan, J. P. Azulay et al., “Nonmotor fluctuations in Parkinson's disease: frequent and disabling,” Neurology, vol. 59, no. 3, pp. 408–413, 2002. View at Scopus
  10. L. M. Shulman, R. L. Taback, A. A. Rabinstein, and W. J. Weiner, “Non-recognition of depression and other non-motor symptoms in Parkinson's disease,” Parkinsonism and Related Disorders, vol. 8, no. 3, pp. 193–197, 2002. View at Publisher · View at Google Scholar · View at Scopus
  11. C. G. Goetz, “The Unified Parkinson's Disease Rating Scale (UPDRS): status and recommendations,” Movement Disorders, vol. 18, no. 7, pp. 738–750, 2003. View at Publisher · View at Google Scholar · View at Scopus
  12. K. R. Chaudhuri, P. Martinez-Martin, A. H. V. Schapira et al., “International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson's disease: the NMSQuest study,” Movement Disorders, vol. 21, no. 7, pp. 916–923, 2006. View at Publisher · View at Google Scholar · View at Scopus