Redefining Treatment Success in Patients With Parkinson’s Disease
SYMPTOM-BASED CRITERIA FOR EVALUATING PD
Rating scales have been developed to evaluate the progression of motor impairment and physical disability in patients with PD and to monitor responses to treatment.22-24 The Hoehn and Yahr scale ranges from 0 (no signs of disease) to 5 (symptoms on both sides of body and wheelchair-bound or confined to bed unless assisted) and is valuable for broadly classifying the disease severity of patients with PD.2,23 The Unified Parkinson’s Disease Rating Scale (UPDRS) is widely used for assessing disability and impairment in patients with PD, particularly in clinical trials.22,24,25 The scale consists of 4 sections that assess behavior and mood, activities of daily living, motor symptoms, and complications of therapy (Figure 2).25-27 The first 3 sections comprise individual items that are rated on a 5-point scale (0 [no disability] to 4 [maximum disability]), with a maximum score of 175 for these 3 sections.26 Higher UPDRS scores reflect more severe disease. The fourth section of the scale is used to evaluate patients with more advanced disease who are receiving drug treatment.25 The UPDRS is often used in conjunction with other measures (eg, Hoehn and Yahr score) to evaluate motor symptoms and clinical status in patients with PD.
Figure 2. UPDRS maximum points distribution by symptom category. UPDRS, Unified Parkinson’s Disease Rating Scale.a Other includes anorexia, nausea, vomiting, sleep abnormalities, and symptomatic orthostasis.25-27
While the UPDRS has proven beneficial for assessing drug efficacy and evaluating patients’ symptom progression, treatment success using this scale is defined primarily on the basis of control of motor symptoms.25 In 2001, the Movement Disorder Society (MDS) conducted a survey of MDS members and found that 96% of 185 responders had used the UPDRS, 87% had applied it in clinical trials, 70% incorporated it into clinical practice, and 69% used it in other research settings. Strengths of the UPDRS included broad application across the multiple clinical stages of PD and comprehensive assessment of motor symptoms, reliability, and validity. Despite these numerous strengths, key weaknesses highlighted were ambiguities in response-scale descriptors, poor inter-rater reliability for some items, and importantly, the lack of items assessing nonmotor aspects of PD. These weaknesses were addressed in a revised version of the scale proposed by the MDS.22 The revised version, the MDS-UPDRS, retains the 4-part structure and total summed score of the UPDRS but has been modified to integrate nonmotor features of PD by including nonmotor experiences of daily living, motor experiences of daily living, motor examination, and motor complications. Like the original version, these items are evaluated on a 5-point scale (0 [normal] to 4 [severe]), with a total time to complete the assessment remaining approximately 30 minutes. The MDS-UPDRS requires clinimetric testing and validation before it can replace the original scale.
Nonmotor symptoms such as olfactory deficit (ie, anosmia) and constipation have been proposed as selective, early signs of PD (Table 2).28 The recognition of these subtle clinical correlates may provide the opportunity to make an early diagnosis before the appearance of extrapyramidal motor symptoms that are characteristic of PD. Despite improvements in the widely applied symptom-based criteria, there is an unmet need for rating scales that focus on nonmotor symptoms in the early diagnosis and management of PD.29 The Scales for Outcomes in Parkinson’s Disease is available to evaluate both nonmotor and motor symptoms for specific clinical outcomes (eg, sleep abnormalities, autonomic dysfunction, psychiatric complications).28,30 Additionally, the PD Nonmotor Symptom Questionnaire was recently validated in a multicenter, observational clinical study of 545 patients with PD.31 These scales may provide a more comprehensive assessment of nonmotor symptoms, thus supplementing the findings of the UPDRS.
Table 2. Early Nonmotor Signs of Parkinson's Disease28
| Probable early signs | Possible early signs |
|---|---|
| Constipation Olfactory deficit REM sleep behavior disorder Depression | Apathy Fatigue Anxiety |
PD, Parkinson’s disease; REM, rapid eye movement.
