Johan Marinus

Validation of proposed diagnostic criteria (the “Budapest Criteria”) for Complex Regional Pain Syndrome

&NA; Current IASP diagnostic criteria for CRPS have low specificity, potentially leading to overdiagnosis. This validation study compared current IASP diagnostic criteria for CRPS to proposed new diagnostic criteria (the “Budapest Criteria”) regarding diagnostic accuracy. Structured evaluations of CRPS‐related signs and symptoms were conducted in 113 CRPS‐I and 47 non‐CRPS neuropathic pain patients. Discriminating between diagnostic groups based on presence of signs or symptoms meeting IASP criteria showed high diagnostic sensitivity (1.00), but poor specificity (0.41), replicating prior work. In comparison, the Budapest clinical criteria retained the exceptional sensitivity of the IASP criteria (0.99), but greatly improved upon the specificity (0.68). As designed, the Budapest research criteria resulted in the highest specificity (0.79), again replicating prior work. Analyses indicated that inclusion of four distinct CRPS components in the Budapest Criteria contributed to enhanced specificity. Overall, results corroborate the validity of the Budapest Criteria and suggest they improve upon existing IASP diagnostic criteria for CRPS.

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.

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.

A short scale for the assessment of motor impairments and disabilities in Parkinson’s disease: the SPES/SCOPA

Objectives: To evaluate the reliability and validity of the Short Parkinson’s Evaluation Scale (SPES)/SCales for Outcomes in Parkinson’s disease (SCOPA)—a short scale developed to assess motor function in patients with Parkinson’s disease (PD). Methods: Eighty five patients with PD were assessed with the SPES/SCOPA, Unified Parkinson’s Disease Rating Scale (UPDRS), Hoehn and Yahr (H&Y) scale, and Schwab and England (S&E) scale. Thirty four patients were examined twice by two different assessors who were blinded to each other’s scores and test executions. Additionally, six items of the motor section of the SPES/SCOPA were assessed in nine patients and recorded on videotape to evaluate inter-rater and intra-rater reliability. Results: The reproducibility of the sum scores in the clinical assessments was high for all subscales of the SPES/SCOPA. Inter-rater reliability coefficients for individual items ranged from 0.27–0.83 in the motor impairment section, from 0.58–0.82 in the activities of daily living section, and from 0.65–0.92 in the motor complications section. Inter-rater reliability of the motor items in the video assessments ranged from 0.70–0.87 and intra-rater reliability ranged from 0.81–0.95. The correlation between related subscales of the SPES/SCOPA and UPDRS were all higher than 0.85, and both scales revealed similar correlations with other measures of disease severity. The mean time to complete the scales differed significantly (p<0.001) and measured 8.1 (SD 1.9) minutes for the SPES/SCOPA and 15.6 (SD 3.6) minutes for the UPDRS. Conclusion: The SPES/SCOPA is a short, reliable, and valid scale that can adequately be used in both research and clinical practice.

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.

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.

Clinical subtypes of Parkinson's disease.

The clinical heterogeneity of Parkinsons disease (PD) may point at the existence of subtypes. Because subtypes likely reflect distinct underlying etiologies, their identification may facilitate future genetic and pharmacotherapeutic studies. Aim of this study was to identify subtypes by a data‐driven approach applied to a broad spectrum of motor and nonmotor features of PD. Data of motor and nonmotor PD symptoms were collected in 802 patients in two different European prevalent cohorts. A model‐based cluster analysis was conducted on baseline data of 344 patients of a Dutch cohort (PROPARK). Reproducibility of these results was tested in data of the second annual assessment of the same cohort and validated in an independent Spanish cohort (ELEP) of 357 patients. The subtypes were subsequently characterized on clinical and demographic variables. Four similar PD subtypes were identified in two different populations and are largely characterized by differences in the severity of nondopaminergic features and motor complications: Subtype 1 was mildly affected in all domains, Subtype 2 was predominantly characterized by severe motor complications, Subtype 3 was affected mainly on nondopaminergic domains without prominent motor complications, while Subtype 4 was severely affected on all domains. The subtypes had largely similar mean disease durations (nonsignificant differences between three clusters) but showed considerable differences with respect to their association with demographic and clinical variables. In prevalent disease, PD subtypes are largely characterized by the severity of nondopaminergic features and motor complications and likely reflect complex interactions between disease mechanisms, treatment, aging, and gender.