Assessing self-awareness of dyskinesias in Parkinson s disease through movie materials

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1 Assessing self-awareness of dyskinesias in Parkinson s disease through movie materials Emilia J. Sitek, MA, PhD a,b Witold Soltan, MD b Dariusz Wieczorek, MA, PhD c Piotr Robowski, MD a,b Michal Schinwelski, MD a,b Jaroslaw Slawek, MD, PhD a,b a Department of Neurological and Psychiatric Nursing, Medical University of Gdansk, Poland b St Adalbert Hospital, Neurology Department, Gdansk, Poland c Department of Rehabilitation, Medical University of Gdansk, Poland Corresponding author: Emilia J. Sitek St Adalbert Hospital Neurology Dpt. Al. Jana Pawla II Gdansk Poland emsitek@gmail.com Summary The aim of our study was to determine self-awareness of dyskinesias and other core motor symptoms in Parkinson s disease (PD) through the use of movie presentations. A scale based on 10 movies (five depicting dyskinesias and five showing core symptoms) and the Self-Assessment Parkinson s Disease Disability Scale were administered to 21 patients (all with a Mini-Mental State Examination MMSE score 25). Neurological assessment included the Unified Parkinson s Disease Rating Scale and the Hoehn-Yahr and Schwab-England scales. In addition, the MMSE, Beck Depression Inventory and Stroop task were administered. Overall, patient and caregiver ratings of dyskinesias and core PD symptoms were consistent. Two patients (9%) completely denied dyskinesias, while four patients (19%) significantly underestimated their dyskinesias. Our results confirm that poor self-awareness of symptoms in PD may be selective and that denial of dyskinesias affects only a minority of patients with normal cognitive status (MMSE 25). Most patients are aware of the presence of dyskinesias. Poor self-awareness of dyskinesias is associated with longer disease duration. KEY WORDS: awareness of movement disorders, dyskinesias, Parkinson s disease, self-awareness Introduction Advanced Parkinson s disease (PD) is characterised by significant motor fluctuations and dyskinesias (1). Selfawareness of dyskinesias in PD is supposed to be limited (2,3). However, in previous studies, patients were asked questions about dyskinesias verbally, without visual presentation of symptoms, an approach which is prone to give rise to misunderstandings: first of all, raters use precise, technical terms to describe dyskinesias, whereas patients often refer to dyskinesias in vague, lay terms. Whereas some report choreic or involuntary jerky or tremor-like movements, others, in describing them, will refer to dancing or swimming. It is very difficult for the examiner, in a structured interview or in a questionnaire, to ask questions that would be understood by all PD patients experiencing dyskinesias. Thus, verbal questions about dyskinesias may be invalid and lead to underreporting of this symptom. The most recent paper on this topic shows that PD patients demonstrate greater awareness of symptoms in the off state (hypokinesia) than in the on state with dyskinesia (3). Self-awareness of symptoms in PD decreases with disease severity (4,5). The aim of the present study was to determine patients self-awareness of dyskinesias and core motor PD symptoms through visual demonstration (film) of each symptom to ensure adequate comprehension of the test items. Moreover, self-awareness of dysfunction in activities of daily living (ADL) was also assessed. Finally, the possible association of poor self-awareness of dyskinesias with cognitive control deficits and depressed mood was addressed. The clinical picture of mild cognitive impairment in PD usually includes executive dysfunction (6), while depression is one of the most prevalent nonmotor manifestations of the disease (7). It was hypothesised that deficits in the monitoring of one s own behaviour may contribute to poor self-awareness of symptoms, while depressed mood may favour overestimation of symptoms. Materials and methods Participants Twenty-one patients (11 women, 10 men, mean age: 63.29±8.82 years; range 40-78) with idiopathic PD and 21 proxies participated in the study. The patients demographic and clinical characteristics are presented in Table I (over). The patients were recruited from the outpatient Department of Movement Disorders at St Adalbert Hospital in Gdansk, Poland. The patients were selected consecutively on the basis of the presence of dyskinesias and their consent to participate in the study. Clinical diagnosis, supported by neuroimaging (computed tomography or magnetic resonance imaging to exclude other pathologies), was established by a movement disorders specialist. The patients received levodopa with benserazide/carbidopa, and in some cases also dopamine agonists (ropinirole, piribedil). The inclusion criteria were good clinical response to levodopa with presence of peak-of-dose dyskinesia (patients Functional Neurology 2011; 26(3):

2 E.J. Sitek et al. scoring at least 1 point in Unified Parkinson s Disease Rating Scale item 32) (Table I). Patients were excluded from the study if they had concurrent neurological or psychiatric dysfunction, were receiving anticholinergic medication, presented past or present alcohol abuse, or previous neurosurgery procedures (including brain stimulation and/or pallidotomy/ thalamotomy), or had a Mini-Mental State Examination (MMSE) score below 25. The proxies comprised 14 partners and 7 children. Procedure The patients and their proxies filled in the questionnaires independently. The patients and their caregivers provided written consent to their participation in the study. Neurological examination was performed in the on phase. The study protocol was approved by the ethics committee of the Medical University of Gdansk. Assessment of self-awareness of symptoms The questionnaires filled in by both the patient and his/her proxy included: a scale based on 10 movies depicting moderate intensity of symptoms [two series of five films depicting, respectively, dyskinesia items from the Unified Huntington s Disease Rating Scale (UHDRS) (8) and items from the Unified Parkinson s Disease Rating Scale (UPDRS) (9)] and the Self-Assessment Parkinson s Disease Disability Scale (SPDDS) (10), comprising 24 items (score ). The UPDRS items were filmed examples of hand and leg tremor, posture abnormalities, bradykinesia and gait impairment, while the dyskinesia items depicted dyskinesias of the trunk, lower limbs, upper limbs and face. The movies were presented in random order. With reference to the patient s own presentation over the previous month, the patient/caregiver was required to rate each of the movie-depicted symptoms as absent (=0), less pronounced than in the movie (=1), of more or less similar intensity (=2), or as more pronounced than in the movie (=3). The maximum score for parkinsonian symptoms, as well as for dyskinesias was 15. Moreover, both the patients and the caregivers were asked, separately, questions from the UPDRS concerning duration (item 32) and disability due to dyskinesias (item 33). In each scale used, a higher score corresponded to a greater intensity of symptoms. The degree of selfawareness in each domain was assessed by comparing the patient s rating with that of his/her caregiver. In each case, the caregiver s score was subtracted from the patient s score. Thus, results below 0 indicated underestimation of deficits, and results above 0 overestimation of deficits. As the SPDDS score is based on a substantially greater amount of items than the movie-based score, Table 1 - Patients demographic and clinical characteristics No. Gender Age Education Disease UPDRS UPDRS UPDRS HY SE levodopa ropinirole piribedil (years) duration -II -III, on -IV dose dose dose (years) (mg) (mg) (mg) 1 M F M F F M M M F F F M M F M F F F F M M M (SD) (8.82) (3.80) (4.73) (6.09) (8.69) (2.49) (7.00) (367) (1.64) (26.35) Abbreviations: UPDRS=Unified Parkinson s Disease Rating Scale; HY=Hoehn-Yahr disease stage; SE=Schwab-England scale score. 122 Functional Neurology 2011; 26(3):

3 Self-awareness of dyskinesias in PD the patient-caregiver discrepancies were computed for each item separately and the average patient-proxy discrepancy was used for further analyses. Neurological assessment Neurological assessment, performed by neurologists experienced in assessing patients with PD, comprised a general neurological examination and UPDRS parts II- IV, and the Hoehn-Yahr and Schwab-England (SE) scales. Neuropsychological assessment Neuropsychological assessment, performed by a neuropsychologist, addressed global cognitive function (MMSE) with age and education correction (11), cognitive control (Stroop task the proportion of uncorrected errors to reactions in the interference trial, the time difference between the execution of interference and colour naming) and mood (Beck Depression Inventory BDI). Statistical analysis The comparisons of patient and caregiver ratings were performed using the t-test or Wilcoxon signed-rank test, depending on the data distribution. Multiple comparisons of discrepancies were performed using the Friedman test. Spearman correlation coefficient was used to assess the relationship between self-awareness of symptoms and clinical variables. The alpha level was set at 5% (p<0.05). Results Patient-proxy ratings of motor symptoms and ADL dysfunction Overall, patient-proxy ratings of dyskinesias, core Parkinsonian symptoms and ADL dysfunctions were relatively consistent. When global scores were considered, the patients and the caregivers did not substantially differ in their assessment, based on the movie presentations, of the intensity of the patients dyskinesias (t=-.44; p=.66) or core PD symptoms (t=-.61; p=.55). The same applies to duration of dyskinesias (z=-.60; p=0.55) and disability caused by dyskinesias (t=-1.60; p=.12), which was assessed through the UPDRS questions. However, as indicated by the average patient-proxy discrepancies (in the movie presentation-based assessments), the PD patients did show a non-significant tendency to underestimate core PD symptoms and to overestimate dyskinesias in terms of intensity (Table II, over) (t=1.42; p=.17). Again, the discrepancy in the assessment of dyskinesia intensity did not differ from the discrepancy in patientproxy ratings of disability due to dyskinesias (t=.30; p=.77) or duration of dyskinesias (z=-.93; p=0.35). Patient and caregiver ratings of ADL in the SPDDS were globally comparable (t=-.30; p=.76). Correlation of patient and proxy ratings with objective measures of motor function Subsequent correlation analysis of patient and caregiver ratings with UPDRS scores and SE scale score revealed that no movie-based dyskinesia ratings correlated with UPDRS measures. In the assessment of the intensity of core PD symptoms, the caregiver ratings correlated with the UPDRS II-IV summed score (rho=.45; p=0.04). Patient ratings of dyskinesia duration and disability showed no associations with UPDRS or SE scores, while caregiver-rated duration of dyskinesias correlated with SE score (rho=-.52; p=.02) and UPDRS IV score (rho=.53; p=.01). Similar associations emerged between disability due to dyskinesias and SE score (rho=-.46; p=.04), UPDRS II (rho=.44; p=.04) and UPDRS II-IV summed score (rho=.48; p=.03). Denial and poor self-awareness of dyskinesias Analysis of raw data showed that only two patients (9%) completely denied dyskinesias (chose absence of dyskinesias when shown each of the five dyskinesia movies), while nine (43%) rated the intensity of their dyskinesias as less severe than the corresponding ratings provided by the proxies (Table II). Correlations between measures of self-awareness of dyskinesias, cognitive control and clinical variables In order to analyse a possible relationship between poor self-awareness of dyskinesias, cognitive control and clinical variables, an additional variable was computed dyskinesia unawareness score (DUS), summing the patient-caregiver discrepancy in the assessment of both intensity (based on the movie presentations) and duration of dyskinesias (UPDRS-32). The DUS averaged (±3.92). Subsequently, DUS was correlated with the patient s age, years of education, disease duration, all UPDRS scores, SE score, daily levodopa dose, MMSE corrected score, BDI score and two cognitive control scores. The only significant association identified was between poor self-awareness of dyskinesias and disease duration (rho=-.45; p=.04). Co-occurrence of poor self-awareness of dyskinesias and ADL dysfunction Patients who had DUS of 4 or higher (as the SD for this variable was 3.92) were considered to have very poor self-awareness of dyskinesias. Patients who had SPDDS average difference scores below (as the SD for this variable was 0.75) were rated as significantly underestimating ADL dysfunction. On the basis of these arbitrary criteria, three (14%) of the 21 patients underestimated both dyskinesias and ADL dysfunction, one patient (5%) underestimated only dyskinesias and three individuals (14%) showed underestimation solely of ADL dysfunction. Overall, 19% of the patients significantly underestimated dyskinesias. Discussion As the presence of dyskinesias is regarded as one of the significant complications of levodopa pharmacotherapy, the determination of patient self-awareness of dyskinesias and of their relationship to daily dysfunction is an important aspect of the debate on the Functional Neurology 2011; 26(3):

4 E.J. Sitek et al. Table 2 - Patient-caregiver discrepancies in ratings of core Parkinson s disease symptoms, dyskinesias and activities of daily living (SPDDS) Patients scores Patient-caregiver discrepancies No. MMSE BDI UPDRS movie ratings UPDRS dyskinesia SPDDS 2 underestimation of score score II-IV items dyskinesias/ daily disability intensity intensity of duration disability of core PD dyskinesias 1 (item 32) 1 (item 33) 1 symptoms no/no no/no no/no no/no no/no yes/yes yes/yes no/no no/yes no/no no/no no/no no/no no/no no/no yes/no no/no no/yes yes/yes no/no no/yes M yes/yes (SD) (1.86) (8.97) (12.61) (0.64) (0.63) (1.44) (1.36) (0.75) 3- no/yes 1-yes/no Abbreviations: MMSE=Mini-Mental State Examination; BDI=Beck Depression Inventory; UPDRS=Unified Parkinson s Disease Rating Scale; SPDDS=Self-Assessment Parkinson s Disease Disability Scale 1 patient-proxy discrepancy is given as a difference score (patient rating minus caregiver rating) 2 patient-proxy discrepancy is given as an average patient-proxy discrepancy across all the items (patient rating minus caregiver rating in each item, divided by 24, the number of items in the SPDDS) gold standard for pharmacotherapy in PD, especially in newly-diagnosed patients. Dyskinesia presence or intensity are also important outcome measures in most clinical trials. Since some patients do not complain of dyskinesias (due to underestimation of the phenomenon), the presence of dyskinesias should not be regarded as an important side effect in all cases. The importance of dyskinesias should be assessed with reference to ADL dysfunction and patient perception of the symptom. The results of the present study show that in the on state, patient perceptions of the intensity of dyskinesias and core PD symptoms are consistent with caregiver ratings. This is the first study addressing self-awareness of dyskinesias assessed using movie materials. The use of movie presentations makes the study more objective, because in verbal questioning dyskinesias may be mistaken for other hyperkinesias, e.g. tremor. Our study failed to prove a global tendency to underestimate dyskinesias in PD patients with relatively normal MMSE. However, it showed that this tendency is present in a minority of patients. As in previous studies, some patients demonstrated underestimation of dyskinesias (2,3). In the study by Vitale et al., 69% of patients (9 out of 13) underestimated dyskinesias: 38% (5 cases) were completely unaware of them, while 31% (4 cases) were partially aware of them (2). Amanzio et al., in their study, showed that 64% of patients (16 out of 25) underestimated dyskinesias to some extent (3). In our study, two patients (9%) denied the presence of dyskinesias and nine (43%) rated the intensity of their dyskinesias as less severe than did their proxies. Nineteen percent of the patients were judged to significantly underestimate their dyskinesias. The comparison of our results with those obtained in the previous studies shows that the self-awareness of dyskinesias varies among individuals, and that approximately half of patients tend to underestimate their dyskinesias to some 124 Functional Neurology 2011; 26(3):

5 Self-awareness of dyskinesias in PD extent. The lower frequency of underestimation of dyskinesias in our study compared with the previous ones may be related to the visual presentation of the symptoms, an approach that may have been, for patients, more understandable than verbal questioning. Unlike Amanzio et al. (3), we did not find a greater unawareness of dyskinesias than of core PD symptoms. This may be due to the fact that Amanzio et al. (3) included only a hypo-bradykinesia index, while in our study two items addressing tremor were included. Taken together, self-awareness of dyskinesias in PD varies individually and different aspects of dyskinesias, such as their intensity, duration and disability should be included in studies dealing with self-awareness of dyskinesias. In our study, caregiver ratings of dyskinesias and core PD symptoms were associated with objective measures, while patient ratings were not. This suggests a slightly deficient self-awareness of motor symptoms in PD patients. This discrepancy may also be related to the small sample size in our study and to inter-subject variability of self-awareness (e.g. denial of symptoms in some patients), as correlation analysis is very sensitive to outliers and we did not decide to exclude any of the patient-caregiver pairs from the analysis. The relationship between dyskinesias and quality of life (QoL) has not been fully elucidated. Few studies confirmed a lack of association between dyskinesias and QoL (12,13). Greater intensity of dyskinesias (as reported by the patients) is associated with depressed mood (14). On the other hand, dopamine dysregulation syndrome in patients with dyskinesias may be associated with euphoria (15), which may explain the discrepancy of results concerning the relationship between dyskinesias and QoL. This relationship seems to be mediated by psychological variables, such as stigmatisation (16). This stigma-related perception of dyskinesias could provide a good explanation for the tendencies observed in our study. The patients were more likely to overestimate the intensity of their dyskinesias and to underestimate their duration and related disability. Obviously, the intensity of dyskinetic movements is more likely to be associated with stigma than their duration and related disability, which have a greater impact on the affected individual than on strangers. Our study addressed perception of three aspects of dyskinesias (intensity, duration, disability). It seems that patients are distressed by greater intensity of dyskinesias, but less so by their duration and by the disability they cause, as this disability is, for them, less distressing than disability experienced in the off phase. In our study unawareness of dyskinesias was not significantly related to depressed mood. Patients with depressed mood may perceive dyskinesias as a more significant problem, while patients with elevated mood (e.g. with dopamine dysregulation syndrome) may ignore the presence of dyskinesias and their perception by others, because of the rewarding effect of the drug. The association of overestimation of dyskinesias with depressed mood was not found in our sample. It is hoped that future research with a larger patient sample will verify the relationship between mood (both elevated and depressed) and perception of dyskinesias. Association of deficient cognitive monitoring with poor self-awareness of dyskinesias was not proven in our study in contrast to the study by Amanzio et al. (3). This lack of association cannot be explained by small sample size, as the size of our sample was comparable to that of the cited paper. The present study has several shortcomings. First, the studied sample was relatively small, albeit not substantially smaller than those used in previous studies on selfawareness of dyskinesias (2,3). Thus, the sample size may account for the non-significant discrepancy found between patient and caregiver ratings. Second, no data on the caregivers, such as mood or cognitive status, were included in the analysis. Caregiver burden may have led to overestimation of the patients dysfunction. Additionally, medication regimens in our group were different and the small sample size did not allow us to analyse the influence of all medications on self-awareness of dyskinesias. The clinical group in our study was heterogenous in terms of disease duration and disease severity, albeit rather homogenous in terms of cognitive status. Selfawareness of dyskinesias was shown to be negatively influenced by disease duration in our study. Further studies are needed to confirm this finding, as the association found was rather weak. The decision to devise a movie-based scale using UPDRS and UHDRS teaching tapes was determined by the fact that when we planned our research, the Unified Dyskinesia Rating Scale (UDysRS) (17,18) was not available. In the future, it would be better to use the UDysRS for research of this kind. UHDRS films were chosen in order to show pure choreic movements, in the absence of other motor symptoms, e.g. tremor or postural abnormalities. Our study, with its novel approach (the use of movies to present abnormal movements), adds to the growing body of literature on patient-proxy agreement in assessing motor symptoms and disability in PD, showing that underestimation of symptoms in PD may be selective and does not concern all patients; moreover, it is related to disease duration. Since dyskinesias may be perceived differently by patients and by those around them, in clinical trials they should be assessed both subjectively and objectively. If videotaping of the patients and real-life observation is impossible due to technical and time constraints, showing patients and their proxies movies presenting dyskinesias seems to be the best alternative for assessing the presence and intensity of dyskinesias in PD patients. The significance of dyskinesias should be assessed not only taking into account their duration and related disability, but also the stigma that is possibly related to their intensity, which is not explicitly assessed by UPDRS and may be assessed through movie materials. As indicated, future studies could benefit from the recently introduced UDysRS (17,18), which was not available at the beginning of our study. Our study results suggest that patients should be interviewed about dyskinesias using detailed descriptions of the various kinds of movement, and that examiners should avoid using professional terms (like dyskinesias or involuntary movements) and, if possible, should make use of visual aids. In conclusion, in PD patients with normal MMSE scores, self-awareness of dyskinesias is relatively well preserved. Only a minority of patients deny dyskinesias. Underestimation of dyskinesias is associated with longer disease duration. The assessment of dyskinesias Functional Neurology 2011; 26(3):

6 E.J. Sitek et al. in PD patients requires a very careful interview with questions describing dyskinesias in terms comprehensible to neurologically-naïve individuals and if possible with the support of visual aids, in order to ensure better understanding. Acknowledgements We are very grateful to the Movement Disorder Society and to Dr Ralf Reilmann from the European Huntington s Disease Network Motor Phenotype Working Group for giving us permission to use movie sequences from their training tapes for neurologists. EJS was supported by a START scholarship awarded by the Foundation for Polish Science while preparing the manuscript. References 1. Jankovic J. Motor fluctuations and dyskinesias in Parkinson s disease: clinical manifestations. Mov Disord 2005; 20 (Suppl 11):S Vitale C, Pellecchia MT, Grossi D et al. Unawareness of dyskinesias in Parkinson s and Huntington s diseases. Neurol Sci 2001;22: Amanzio M, Monteverdi S, Giordano A, Soliveri P, Filippi P, Geminiani G. Impaired awareness of movement disorders in Parkinson s disease. Brain Cogn 2010;72: Martínez-Martín P, Benito-Lefin J, Alonso F et al. Patients, doctors, and caregivers assessment of disability using the UPDRS-ADL section: are these ratings interchangeable? Mov Disord 2003;18: Fleming A, Cook KF, Nelson ND, Lai EC. Proxy reports in Parkinson s disease: caregiver and patient self-reports of quality of life and physical activity. Mov Disord 2005;20: Caviness JN, Driver-Dunckley E, Connor DJ et al. Defining mild cognitive impairment in Parkinson s disease. Mov Disord 2007;22: Ziemssen T, Reichmann H. Non-motor dysfunction in Parkinson s disease. Parkinsonism Relat Disord 2007;13: Reilmann R, Roos RA, Rosser A et al. A teaching film, video library and online certification for the Unified Huntington s Disease Rating Scale Total Motor Score. Aktuelle Neurologie 2009;3(S2): Goetz CG, Stebbins GT, Chmura TA, Fahn S, Klawans HL, Marsden CD. Teaching tape for the motor section of the unified Parkinson s disease rating scale. Mov Disord 1995; 10: Brown RG, MacCarthy B, Jahanshahi M, Marsden CD. Accuracy of self-reported disability in patients with Parkinsonism. Arch Neurol 1989;46: Mungas D, Marshall SC, Weldon M, Haan M, Reed BR. Age and education correction of Mini-Mental State Examination for English and Spanish-speaking elderly. Neurology 1996;46: Schrag A, Jahanshahi M, Quinn N. How does Parkinson s disease affect quality of life? A comparison with quality of life in the general population. Mov Disord 2000; 15: Dodel RC, Berger K, Oertel WH. Health-related quality of life and healthcare utilisation in patients with Parkinson s disease: impact of motor fluctuations and dyskinesias. Pharmacoeconomics 2001;19: Pechevis M, Clarke CE, Vieregge P et al.; Trial Study Group. Effects of dyskinesias in Parkinson s disease on quality of life and health-related costs: a prospective European study. Eur J Neurol 2005;12: Voon V, Fernagut PO, Wickens J et al. Chronic dopaminergic stimulation in Parkinson s disease: from dyskinesias to impulse control disorders. Lancet Neurol 2009;8: Montel S, Bonnet AM, Bungener C. Quality of life in relation to mood, coping strategies, and dyskinesia in Parkinson s disease. J Geriatr Psychiatry Neurol 2009;22: Goetz CG, Nutt JG, Stebbins GT. The Unified Dyskinesia Rating Scale: presentation and clinimetric profile. Mov Disord 2008;23: Goetz CG, Nutt JG, Stebbins GT, Chmura TA. Teaching program for the Unified Dyskinesia Rating Scale. Mov Disord 2009;24: Functional Neurology 2011; 26(3):