Bob van Hilten

Systematic evaluation of rating scales for impairment and disability in Parkinson's disease

We assessed the clinometric characteristics of rating scales used for the evaluation of motor impairment and disability of patients with Parkinsons disease (PD), conducting a systematic review of PD rating scales published from 1960 to the present. Thirty studies describing clinometrics of 11 rating scales used for PD were identified. Outcome measures included validity (including factor structure), reliability (internal consistency, inter‐rater, and intrarater) and responsiveness. We traced three impairment scales (Webster, Columbia University Rating Scale [CURS] and Parkinsons Disease Impairment Scale), four disability scales (Schwab and England, Northwestern University Disability Scale [NUDS], Intermediate Scale for Assessment of PD, and Extensive Disability Scale), and four scales evaluating both impairment and disability (New York University, University of California Los Angeles, Unified Parkinsons Disease Rating Scale [UPDRS], and Short Parkinson Evaluation Scale). The scales showed large differences in the extent of representation of items related to signs considered responsive to dopaminergic treatment or to those signs that appear late in the disease course and lack responsiveness to treatment. Regardless of the scale, there was a conspicuous lack of consistency concerning inter‐rater reliability of bradykinesia, tremor, and rigidity. Overall disability items displayed moderate to good inter‐rater reliability. The available evidence shows that CURS, NUDS, and UPDRS have moderate to good reliability and validity. In contrast to their widespread clinical use for assessment of impairment and disability in PD, the majority of the rating scales have either not been subjected to an extensive clinometric evaluation or have demonstrated clinometric shortcomings. The CURS, NUDS, and UPDRS are the most evaluated, valid, and reliable scales currently available.

Intrathecal Baclofen for the Treatment of Dystonia in Patients with Reflex Sympathetic Dystrophy

BACKGROUND AND METHODS Patients with reflex sympathetic dystrophy (also known as the complex regional pain syndrome) may have dystonia, which is often unresponsive to treatment. Some forms of dystonia respond to the intrathecal administration of baclofen, a specific gamma-aminobutyric acid-receptor (type B) agonist that inhibits sensory input to the neurons of the spinal cord. We evaluated this treatment in seven women who had reflex sympathetic dystrophy with multifocal or generalized tonic dystonia. First, we performed a double-blind, randomized, controlled crossover trial of bolus intrathecal injections of 25, 50, and 75 microg of baclofen and placebo. Changes in the severity of dystonia were assessed by the woman and by an investigator after each injection. In the second phase of the study, six of the women received a subcutaneous pump for continuous intrathecal administration of baclofen and were followed for 0.5 to 3 years. RESULTS In six women, bolus injections of 50 and 75 microg of baclofen resulted in complete or partial resolution of focal dystonia of the hands but little improvement in dystonia of the legs. During continuous therapy, three women regained normal hand function, and two of these three women regained the ability to walk (one only indoors). In one woman who received continuous therapy, the pain and violent jerks disappeared and the dystonic posturing of the arm decreased. In two women the spasms or restlessness of the legs decreased, without any change in the dystonia. CONCLUSIONS In some patients, the dystonia associated with reflex sympathetic dystrophy responds markedly to intrathecal baclofen.

Susceptibility loci for complex regional pain syndrome

&NA; An association between HLA‐DR13 and patients with complex regional pain syndrome (CRPS) who progressed towards multifocal or generalized tonic dystonia was recently reported. We now report on a new locus, centromeric in HLA‐class I, which was significantly associated with a spontaneous development of CRPS, suggesting an interaction between trauma severity and genetic factors conferring CRPS susceptibility. Additionally, an association with the D6S1014 locus was found, supporting the previous finding of an association with HLA‐DR13.

Ambulatory objective assessment of tremor in Parkinson's disease.

Continuous ambulatory multichannel accelerometry (CAMCA) has recently been validated for the assessment of hypo-and bradykinesia and body position in patients with Parkinsons disease (PD). This study aims to validate CAMCA for the assessment of resting tremor in patients with PD. First, in seven patients with PD with varying degrees of tremor severity, a tremor detection algorithm was developed. Second, 59 patients with PD and 43 age-matched controls were assessed with CAMCA during 24 hours. Duration and intensity of resting tremor, and measures reflecting hypo-and bradykinesia and body position were calculated for the diurnal period. In part 1 of the study, the tremor detection algorithm had a high sensitivity (0.82) and specificity (0.93). Ambulatory monitoring revealed that categories with higher clinical tremor severity had increased objective values for duration and intensity of tremor. Duration and intensity of tremor were correlated with the clinical score for resting tremor (Spearmans rank correlation: 0.66–0.77). Measures for hypo-and bradykinesia differed between patients and controls, but not between groups of patients defined by tremor severity. This study has validated continuous ambulatory multichannel accelerometry for the assessment of tremor in PD, while simultaneously measuring hypo-and bradykinesia and body position.

A review of the assessment of dyskinesias.

Dyskinesias are most prevalent in patients with Huntingtons disease (HD), patients with Parkinsons disease (PD) who have received chronic levodopa therapy, and in patients who have been treated with neuroleptics (tardive dyskinesia [TD]). Recent therapeutic developments have fueled a growing interest in the clinimetrics of dyskinesias. For dyskinesias in HD, few rating scales are available, but data on validity, reliability, and responsiveness are scarce. Only the interrater reliability of facial dyskinesias has been evaluated and found to be low. Many subjective rating scales for dyskinesias in PD exist, but only the Dyskinesia Rating Scale has undergone sufficient clinimetric evaluation. For TD, numerous rating scales are available, many of them with ample data on reliability and validity. Objective assessment of dyskinesias has been attempted with a number of techniques. All these methods require a laboratory setting, rendering them susceptible to influence of stress. Moreover, they provide only a momentary assessment of dyskinesia severity and fail to take into account diurnal fluctuations. In view of the methodologic shortcomings in the assessment of dyskinesias, more effort needs to be put into strengthening currently available modes of assessment or designing new ones. In the future ambulatory accelerometry might prove to be of value in this field.

Intravenous Magnesium for Complex Regional Pain Syndrome Type 1 (CRPS 1) Patients: A Pilot Study

OBJECTIVES To explore the feasibility of intravenous magnesium administration as a potential candidate intervention for a large size trial in Complex Regional Pain Syndrome Type 1 (CRPS 1). DESIGN Randomized clinical trial. SETTING Outpatient pain clinic. PATIENTS Ten CRPS 1 patients. INTERVENTIONS Eight patients received 70 mg/kg magnesium sulphate infusions in 4 hours for 5 days. For blinding purposes, 2 patients received equal amount NaCl 0.9% solutions (data not analyzed or presented). Interventions were accompanied by standardized physical therapy. OUTCOME MEASURES Pain was assessed using an 11-point Box scale (three times daily for a week) and the McGill Pain Questionnaire. Skin sensitivity was measured with the Semmes Weinstein Monofilaments, (other) impairments with the Impairment Level Sumscore. In addition, functional limitations (Radboud Skills Questionnaire, questionnaire rising and sitting down) and quality of life (Short Form-36 [SF-36], EuroQol) were evaluated. Assessments were performed at baseline, 1, 3, 6, and 12 weeks after intervention. RESULTS Mild systemic side effects were experienced and the infusions were locally well tolerated. Pain was significantly reduced at all follow up compared with baseline (T1: P = 0.01, T3: P = 0.04, T6: P = 0.02, T12: P = 0.02). McGill sensory subscale improved significantly at T1 (number of words chosen: P = 0.03 and pain rating index: P = 0.03). Impairment level (P = 0.03) and quality of life (EuroQol P = 0.04, SF-36 physical P = 0.01) were significantly improved at T12. No improvement was found for skin sensitivity and functional limitations. CONCLUSION Intravenous magnesium significantly improved pain, impairment and quality of life and was well tolerated. The results of this pilot study are encouraging and suggest that magnesium IV as a treatment in CRPS 1 should be further explored in a large size formal trial design.

The efficacy and safety of adjunct bromocriptine therapy for levodopa-induced motor complications: A systematic review

To assess the efficacy and safety of adjunct bromocriptine (BR) compared with placebo in the treatment of patients with Parkinsons disease (PD) who have motor complications.

Response to Drs. Kapural and Stanton-Hicks

ror, technical failure, infection) to achieve comparatively shortterm relief of pain? Who will pay for it, as such lengthy infusions are expensive and seldom reimbursed by the third-party payers? What is considered long-term pain relief in chronic pain management? When it comes to spine care any spinal injections (including epidural steroids), surgeries or various minimally invasive procedures need to justify their cost by demonstrating longterm functional capacity improvements. Journal Spine, for example, accepts for review the articles with at least a one year follow-up. Repeated epidural steroid injections, for example, have been castigated because in similarly disabled patient groups, they have failed to provide long-term (>6 months or 24 weeks) pain relief, although only at a cost of several hundred

Sleep Disruption in Parkinson's Disease: Assessment by Continuous Activity Monitoring

per injection [1,7]. How can then we recommend use of the continuous ketamine infusions over 4 days or more in an inpatient, monitored setting with attendant costs of tens of thousands of US

The role of EDTA in provoking allergic reactions to subcutaneous infusion of apomorphine in patients with Parkinson's disease: A histologic study

? Until future studies can document any real long-term benefit, there are many better therapeutic options for those well-selected group of the patients who suffer from severe CRPS including spinal cord stimulation (SCS) [6,10]. In the latter respect, while entry costs for invasive therapies, such as SCS, may be high, the recent report suggests that over a four-year period the Incremental Cost-Effectiveness Ratio (ICER) per quality adjusted life-year (QALY) gained is reasonable in refractory cases [9].