Restless legs syndrome outside the blood-brain barrier--exacerbation by domperidone in Parkinson's disease.

INTRODUCTION: Models of dopaminergic function in restless legs focus on central dopaminergic neurons. Domperidone, a peripheral dopamine blocker that cannot cross the blood-brain barrier, is commonly used in Parkinson's disease. After encountering a case of restless legs syndrome that dramatically worsened with domperidone, we assessed whether Parkinson's patients may have exacerbation of restless legs with domperidone. METHODS: From two Parkinson's disease cohorts, we assessed restless legs prevalence according to standard criteria, in patients taking vs. not taking domperidone. Regression analysis was performed, adjusting for age, sex, disease duration, UPDRS, dopaminergic medications and other medications. RESULTS: One hundred eighty four patients were assessed, of whom 46 (25%) had restless legs. Thirteen out of twenty seven (48%) patients on domperidone had restless legs compared to 33/157 (21%) without (p = 0.010). Other medications were not associated with restless legs. CONCLUSION: This unexpected finding suggests that dopaminergic neurons outside of the blood-brain barrier may be important in restless legs syndrome pathophysiology.

Validation of the non-motor symptoms questionnaire (NMS-Quest).

BACKGROUND: Although non-motor manifestations of Parkinson's disease are common and can cause severe disability, they are often under-recognized, leading to missed treatment opportunities. Screening tools for non-motor symptoms are urgently needed. Recently a 30-item screening Non Motor Symptoms Questionnaire was developed. Although some psychometric properties have been evaluated, sensitivity and specificity of the questionnaire have not been systematically assessed. METHODS: Parkinson patients completed Non Motor Symptoms Questionnaire, then underwent a gold-standard clinical evaluation of non-motor symptoms and signs that included extensive standardized questionnaires, cognitive/behavioural assessment, and neurological examination to determine whether each manifestation was present or absent. The sensitivity and specificity of each non-motor symptom, in relation to the gold-standard were estimated. RESULTS: For the 70 participants, the mean age was 66.7+/-9.3, 64% were men, and disease duration was 3.8+/-2.8 years. From the gold-standard evaluation, the prevalence of non-motor manifestations ranged from 8.7% (hallucinations) to 78.3% (nocturia). The mean sensitivity of all Non Motor Symptoms was 63.4%. This varied considerably among different manifestations, ranging from 24% (sleepiness, hyposmia) to 100% (diplopia). By restricting analysis to clinically significant non-motor problems (i.e. those serious enough to warrant treatment), the mean sensitivity increased to 71.8%. The specificity for most items was high, with an overall mean specificity of 88.5%. CONCLUSIONS: For many non-motor manifestations Non Motor Symptoms Questionnaire is an effective screen; however, for manifestations such as somnolence, olfactory loss and apathy, sensitivity is suboptimal. Overall, this questionnaire can be a useful clinical tool for screening non-motor problems in an office setting.