Jacobus J. van Hilten

Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Scale Presentation and Clinimetric Testing Results

We present a clinimetric assessment of the Movement Disorder Society (MDS)‐sponsored revision of the Unified Parkinsons Disease Rating Scale (MDS‐UPDRS). The MDS‐UDPRS Task Force revised and expanded the UPDRS using recommendations from a published critique. The MDS‐UPDRS has four parts, namely, I: Non‐motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications. Twenty questions are completed by the patient/caregiver. Item‐specific instructions and an appendix of complementary additional scales are provided. Movement disorder specialists and study coordinators administered the UPDRS (55 items) and MDS‐UPDRS (65 items) to 877 English speaking (78% non‐Latino Caucasian) patients with Parkinsons disease from 39 sites. We compared the two scales using correlative techniques and factor analysis. The MDS‐UPDRS showed high internal consistency (Cronbachs alpha = 0.79–0.93 across parts) and correlated with the original UPDRS (ρ = 0.96). MDS‐UPDRS across‐part correlations ranged from 0.22 to 0.66. Reliable factor structures for each part were obtained (comparative fit index > 0.90 for each part), which support the use of sum scores for each part in preference to a total score of all parts. The combined clinimetric results of this study support the validity of the MDS‐UPDRS for rating PD.

Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan.

This article presents the revision process, major innovations, and clinimetric testing program for the Movement Disorder Society (MDS)–sponsored revision of the Unified Parkinsons Disease Rating Scale (UPDRS), known as the MDS‐UPDRS. The UPDRS is the most widely used scale for the clinical study of Parkinsons disease (PD). The MDS previously organized a critique of the UPDRS, which cited many strengths, but recommended revision of the scale to accommodate new advances and to resolve problematic areas. An MDS‐UPDRS committee prepared the revision using the recommendations of the published critique of the scale. Subcommittees developed new material that was reviewed by the entire committee. A 1‐day face‐to‐face committee meeting was organized to resolve areas of debate and to arrive at a working draft ready for clinimetric testing. The MDS‐UPDRS retains the UPDRS structure of four parts with a total summed score, but the parts have been modified to provide a section that integrates nonmotor elements of PD: I, Nonmotor Experiences of Daily Living; II, Motor Experiences of Daily Living; III, Motor Examination; and IV, Motor Complications. All items have five response options with uniform anchors of 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Several questions in Part I and all of Part II are written as a patient/caregiver questionnaire, so that the total rater time should remain approximately 30 minutes. Detailed instructions for testing and data acquisition accompany the MDS‐UPDRS in order to increase uniform usage. Multiple language editions are planned. A three‐part clinimetric program will provide testing of reliability, validity, and responsiveness to interventions. Although the MDS‐UPDRS will not be published until it has successfully passed clinimetric testing, explanation of the process, key changes, and clinimetric programs allow clinicians and researchers to understand and participate in the revision process.

Clinical features and pathophysiology of complex regional pain syndrome

A complex regional pain syndrome (CRPS)--multiple system dysfunction, severe and often chronic pain, and disability--can be triggered by a minor injury, a fact that has fascinated scientists and perplexed clinicians for decades. However, substantial advances across several medical disciplines have recently improved our understanding of CRPS. Compelling evidence implicates biological pathways that underlie aberrant inflammation, vasomotor dysfunction, and maladaptive neuroplasticity in the clinical features of CRPS. Collectively, the evidence points to CRPS being a multifactorial disorder that is associated with an aberrant host response to tissue injury. Variation in susceptibility to perturbed regulation of any of the underlying biological pathways probably accounts for the clinical heterogeneity of CRPS.

Assessment of autonomic dysfunction in Parkinson's disease: the SCOPA-AUT

We developed a questionnaire to assess autonomic symptoms in patients with Parkinsons disease (PD) and evaluated its reliability and validity. Based on the results of a postal survey in 46 PD patients, 21 multiple system atrophy patients, and 8 movement disorders specialists, items were included according to their frequency, burden, and clinical relevance. The questionnaire was evaluated in 140 PD patients and 100 controls, and test–retest reliability was established in a sample of 55 PD patients. The SCOPA‐AUT consists of 25 items assessing the following regions: gastrointestinal (7), urinary (6), cardiovascular (3), thermoregulatory (4), pupillomotor (1), and sexual (2 items for men and 2 items for women) dysfunction. Test–retest reliability was good. Autonomic problems increased significantly with increasing disease severity for all autonomic regions, except sexual dysfunction. We conclude that SCOPA‐AUT is a reliable and valid questionnaire that evaluates autonomic dysfunction in PD.

Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1.

ABSTRACT Complex Regional Pain Syndrome Type 1 (CRPS‐1) responds poorly to standard pain treatment. We evaluated if the N‐methyl‐d‐aspartate receptor antagonist S(+)‐ketamine improves pain in CRPS‐1 patients. Sixty CRPS‐1 patients (48 females) with severe pain participated in a double‐blind randomized placebo‐controlled parallel‐group trial. Patients were given a 4.2‐day intravenous infusion of low‐dose ketamine (n = 30) or placebo (n = 30) using an individualized stepwise tailoring of dosage based on effect (pain relief) and side effects (nausea/vomiting/psychomimetic effects). The primary outcome of the study was the pain score (numerical rating score: 0–10) during the 12‐week study period. The median (range) disease duration of the patients was 7.4 (0.1–31.9) years. At the end of infusion, the ketamine dose was 22.2 ± 2.0 mg/h/70 kg. Pain scores over the 12‐week study period in patients receiving ketamine were significantly lower than those in patients receiving placebo (P < 0.001). The lowest pain score was at the end of week 1: ketamine 2.68 ± 0.51, placebo 5.45 ± 0.48. In week 12, significance in pain relief between groups was lost (P = 0.07). Treatment did not cause functional improvement. Patients receiving ketamine more often experienced mild to moderate psychomimetic side effects during drug infusion (76% versus 18%, P < 0.001). In conclusion, in a population of mostly chronic CRPS‐1 patients with severe pain at baseline, a multiple day ketamine infusion resulted in significant pain relief without functional improvement. Treatment with ketamine was safe with psychomimetic side effects that were acceptable to most patients.

Evaluation of the hospital anxiety and depression scale in patients with Parkinson's disease.

The purpose of this study was to evaluate the psychometric properties of the Hospital Anxiety and Depression Scale (HADS) in patients with Parkinsons disease (PD) and to assess the prevalence of symptoms of anxiety and depression in this population. The HADS was sent to 205 patients with PD, together with three quality-of-life (QoL) instruments, i.e., the Parkinsons Disease Questionnaire (PDQ-39), the EQ-5D, and a visual analogue scale (VAS). Hospital Anxiety and Depression Scale scores were also compared with Hoehn-Yahr (H&Y) scores. Eighty-six percent of the patients returned the questionnaires. The quality of the data was good. Cronbach &agr; for the HADS was 0.88. Test-retest reliability over 2 weeks was 0.84 for the sum score of the HADS (intraclass correlation coefficient) and ranged from 0.42–0.76 for individual items (weighted kappa). Factor analysis revealed two factors, accounting for 51.9% of the variance. One factor represented anxiety, the other depression. Correlations with PDQ-39, EQ-5D, VAS, and H&Y were 0.72, −0.59, −0.59, and 0.32, respectively (p values < 0.001). Depression scores accounted for 52% of the variance in QoL, whereas disease severity explained 24%. Using the cut-off values proposed by the developers indicated that possible and probable anxiety were present in 29.4% and 19.8% of the patients, respectively. Percentages for possible and probable depression were 21.5 and 16.9. The psychometric performance of the HADS in patients with PD is satisfactory. In addition, almost 50% of the patients displayed symptoms of anxiety, whereas nearly 40% showed signs of depression.

Reliability and validity of the Beck depression inventory in patients with Parkinson's disease

We evaluated the validity, reliability, and potential responsiveness of the Beck Depression Inventory (BDI) in patients with Parkinsons disease (PD). In part 1 of the study, 92 patients with PD underwent a structured clinical interview for DSM major depression and based on this patients were considered depressed (PD‐D) or nondepressed (PD‐ND). Subsequently, patients filled in the BDI. In part 2, a postal survey consisting the BDI was performed in 185 PD patients and 112 controls. Test–retest reliability was assessed in 60 PD patients. The factor analysis revealed a cognitive–affective and a somatic factor. Cronbachs α for the BDI was 0.88. Mean BDI indicated significant differences (P < 0.001) between the PD and control group, between the PD‐ND and PD‐D group, and between PD‐ND and control group. In part 1, the receiver operating characteristic curves showed that the area under the curve for the total BDI was 0.88. A cutoff was calculated for the BDI (14/15) that had the highest sum of sensitivity (0.71) and specificity (0.90). In part 2, the test–retest reliability for the BDI total score was 0.89 (intraclass correlation coefficient). The smallest real difference was 3.3 for the total BDI. The BDI is a valid, reliable, and potential responsive instrument to assess the severity of depression in PD. However, an adjusted cutoff is recommended.

Genome-wide association study confirms extant PD risk loci among the Dutch.

In view of the population-specific heterogeneity in reported genetic risk factors for Parkinsons disease (PD), we conducted a genome-wide association study (GWAS) in a large sample of PD cases and controls from the Netherlands. After quality control (QC), a total of 514 799 SNPs genotyped in 772 PD cases and 2024 controls were included in our analyses. Direct replication of SNPs within SNCA and BST1 confirmed these two genes to be associated with PD in the Netherlands (SNCA, rs2736990: P=1.63 × 10−5, OR=1.325 and BST1, rs12502586: P=1.63 × 10−3, OR=1.337). Within SNCA, two independent signals in two different linkage disequilibrium (LD) blocks in the 3′ and 5′ ends of the gene were detected. Besides, post-hoc analysis confirmed GAK/DGKQ, HLA and MAPT as PD risk loci among the Dutch (GAK/DGKQ, rs2242235: P=1.22 × 10−4, OR=1.51; HLA, rs4248166: P=4.39 × 10−5, OR=1.36; and MAPT, rs3785880: P=1.9 × 10−3, OR=1.19).

Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis

Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD.

Thinking about movement hurts: The effect of motor imagery on pain and swelling in people with chronic arm pain

OBJECTIVE Chronic painful disease is associated with pain on movement, which is presumed to be caused by noxious stimulation. We investigated whether motor imagery, in the absence of movement, increases symptoms in patients with chronic arm pain. METHODS Thirty-seven subjects performed a motor imagery task. Pain and swelling were measured before, after, and 60 minutes after the task. Electromyography findings verified no muscle activity. Patients with complex regional pain syndrome (CRPS) were compared with those with non-CRPS pain. Secondary variables from clinical, psychophysical, and cognitive domains were related to change in symptoms using linear regression. RESULTS Motor imagery increased pain and swelling. For CRPS patients, pain (measured on a 100-mm visual analog scale) increased by a mean +/- SD of 5.3 +/- 3.9 mm and swelling by 8% +/- 5%. For non-CRPS patients, pain increased by 1.4 +/- 4.1 mm and swelling by 3% +/- 4%. There were no differences between groups (P > 0.19 for both). Increased pain and swelling related positively to duration of symptoms and performance on a left/right judgment task that interrogated the body schema, autonomic response, catastrophic thoughts about pain, and fear of movement (r > 0.42, P < 0.03 for all). CONCLUSION Motor imagery increased pain and swelling in patients with chronic painful disease of the arm. The effect increased in line with the duration of symptoms and seems to be modulated by autonomic arousal and beliefs about pain and movement. The results highlight the contribution of cortical mechanisms to pain on movement, which has implications for treatment.