Reduced striatal D2 receptor binding in myoclonus-dystonia.

PURPOSE: To study striatal dopamine D(2) receptor availability in DYT11 mutation carriers of the autosomal dominantly inherited disorder myoclonus-dystonia (M-D). METHODS: Fifteen DYT11 mutation carriers (11 clinically affected) and 15 age- and sex-matched controls were studied using (123)I-IBZM SPECT. Specific striatal binding ratios were calculated using standard templates for striatum and occipital areas. RESULTS: Multivariate analysis with corrections for ageing and smoking showed significantly lower specific striatal to occipital IBZM uptake ratios (SORs) both in the left and right striatum in clinically affected patients and also in all DYT11 mutation carriers compared to control subjects. CONCLUSIONS: Our findings are consistent with the theory of reduced dopamine D(2) receptor (D2R) availability in dystonia, although the possibility of increased endogenous dopamine, and consequently, competitive D2R occupancy cannot be ruled out.

What should be defined as good outcome in stroke trials; a modified Rankin score of 0-1 or 0-2?

BACKGROUND AND PURPOSE: Good outcome in stroke trials has been defined as a modified Rankin scale (mRs) score of 0-1 or 0-2. The aim of this study was to investigate the clinical meaning of these two dichotomies. METHODS: We studied 152 patients six months post stroke using the mRs and a new disability measure the AMC Linear Disability Scale (ALDS) item bank. Descriptive statistics were used to show the ALDS scores by the levels of the mRs. To investigate the clinical meaning of the different definitions of good outcome, the mean probability to perform activities of daily life (ADL) of all mRs grades and these two dichotomies was calculated. RESULTS: The ability to perform difficult ALDS items declined gradually with increasing mRs grade. When favourable outcome is defined as mRs 0-1, 15 % of the cohort has a good outcome; of these patients 84 % were likely to perform outdoor activities. If good outcome is defined as mRs 0-2, the percentage of patients with good outcome increased to 37 %, whereas 66 % of these patients were likely to perform outdoor activities. CONCLUSION: If good outcome is defined as the ability to perform outdoor activities mRs 0-1 should be chosen. If complex ADL are considered as good outcome mRs 0-2 is the outcome measure of choice. Independent of which outcome measure is chosen, the treatment effect in clinical trials must be large before good outcome is achieved. Therefore, it is likely that clinically important treatment effects can be missed in clinical trials with both these mRs endpoints.

The AMC Linear Disability Score in patients with newly diagnosed Parkinson disease.

OBJECTIVE: The aim of this study was to examine the clinimetric properties of the AMC Linear Disability Score (ALDS), a new generic disability measure based on Item Response Theory, in patients with newly diagnosed Parkinson disease (PD). METHODS: A sample of 132 patients with PD was evaluated using the Hoehn and Yahr (H&Y), the Unified PD Rating Scale motor examination, the Schwab and England scale (S&E), the Short Form-36, the PD Quality of Life Questionnaire, and the ALDS. RESULTS: The internal consistency reliability of the ALDS was good (alpha = 0.95) with 55 items extending the sufficient item-total correlation criterion (r > 0.20). The ALDS was correlated with other disability measures (r = 0.50 to 0.63) and decreasingly associated with measures reflecting impairments (r = 0.36 to 0.37) and mental health (r = 0.23 to -0.01). With regard to know-group validity, the ALDS indicated that patients with more severe PD (H&Y stage 3) were more disabled than patients with mild (H&Y stage 1) or moderate PD (H&Y stage 2) (p < 0.0001). The ALDS discriminated between more or less severe extrapyramidal symptoms (p = 0.001) and patients with postural instability showed lower ALDS scores compared to patients without postural instability (p = or< 0.0001). Compared to the S&E (score 100% = 19%), the ALDS showed less of a ceiling effect (5%). CONCLUSION: The AMC Linear Disability Score is a flexible, feasible, and clinimetrically promising instrument to assess the level of disability in patients with newly diagnosed Parkinson disease.