J.J. van Hilten

Assessment of cognition in Parkinson’s disease

Objective: To develop a short, practical instrument that is sensitive to the specific cognitive deficits in Parkinson’s disease (PD) for comparing groups in research situations and for assessing change in cognitive functioning over time. Methods: A literature search was conducted to identify the most frequently affected cognitive domains in PD and to select candidate items for the initial scale. This scale was tested in 85 patients and 75 age-, education-, and sex-matched control subjects. Items that met predefined criteria for data quality, reproducibility, and discriminative properties were included in the final scale. Results: The final scale, the SCOPA-COG (SCales for Outcomes of PArkinson’s disease–cognition), consists of 10 items with a maximum score of 43, with higher scores reflecting better performance. The test–retest reliability of the total score was 0.78 (intraclass correlation coefficient) and ranged from 0.40 to 0.75 for individual items (weighted κ). Cronbach’s α was 0.83. Construct validity of the scale was supported by the expected correlations with the CAMCOG (Cambridge Cognitive Examination) and the Mini-Mental State Examination (MMSE) and by differences found between groups of participants classified by dementia status and between patients grouped by disease severity. The scale showed a clear trend toward lower cognition scores for patients with more advanced PD. The coefficient of variation of the SCOPA-COG was higher than that of the CAMCOG or the MMSE, indicating a better ability to detect differences between individuals. Conclusion: The SCOPA-COG is a short, reliable, and valid instrument that is sensitive to the specific cognitive deficits in PD.

Changes in cerebrospinal fluid levels of pro-inflammatory cytokines in CRPS

&NA; Complex Regional Pain Syndrome (CRPS) Types I and II are characterized by various combinations of sensory, autonomic and motor abnormalities. Pain disproportionate to the severity and duration of the inciting event is the most devastating symptom. In animal studies, conditions resulting in exaggerated pain states demonstrate elevated pro‐inflammatory cytokines. In addition, pro‐inflammatory cytokines have been shown to induce or increase neuropathic and inflammatory pain. Utilizing high sensitivity enzyme linked immunosorbent assay (ELISA), we compared the levels of the pro‐inflammatory cytokines interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6) and Tumor Necrosis Factor‐alpha (TNF‐α) in the cerebrospinal fluid (CSF) of patients afflicted with CRPS to CSF levels found in other patients with and without painful conditions. The results from this study demonstrated significant increases in IL‐1β and IL‐6, but not TNF‐α in the CSF of individuals afflicted with CRPS as compared to controls. CSF cytokine levels in controls with painful conditions did not differ from levels in controls without pain. These increases showed no correlation with the patients gender or weight. These results are consistent with studies that suggest that the pathogenesis of CRPS is due in part to central neuroimmune activation.

Cognitive impairment in Parkinson's disease

Background: Cognitive impairment plays a role in Parkinson’s disease (PD) and has important consequences for patient management. However, many aspects of cognitive impairment in PD remain unclear because of the use of different and often invalid measurement instruments. In this study, a reliable and valid instrument, the SCales for Outcomes in PArkinson’s disease-COGnition (SCOPA-COG), was used. Aim: To evaluate cognitive functioning in a large cohort of patients with Parkinson’s disease and to assess the relations with demographic, disease related and clinical variables. Methods: A cohort of 400 patients with PD was evaluated for cognition, motor and non-motor domains, as well as for demographic and disease related characteristics. Results were compared with 150 controls matched for overall age, sex and education distribution. Results: Patients with PD scored significantly lower on all cognitive subdomains compared with controls, with the largest differences for executive functioning and memory. After correction for age and years of education, 22% of patients had impaired cognition, as measured by the total SCOPA-COG score, compared with controls. Across all patients, more severe cognitive impairment was associated with significantly more impairment in motor, autonomic, depressive and psychotic domains. Patients with the postural instability gait difficulty (PIGD) dominant phenotype showed more cognitive impairment compared with patients with the tremor dominant phenotype. Contrary to tremor scores, PIGD scores significantly worsened with increasing disease severity. Conclusions: Cognition is an important domain of the clinical spectrum of PD and poorer cognitive performance is associated with greater impairment in motor and non-motor domains in PD. The difference in cognitive scores between PIGD dominant patients and tremor dominant patients likely reflects more advanced disease.

Sleep, excessive daytime sleepiness and fatigue in Parkinson's disease

SummaryThe objective of this questionnaire-based survey was to evaluate the prevalence and causes of sleep disturbances in 90 nondepressive patients with Parkinsons disease (PD) and 71 age-matched healthy subjects. We also assessed the prevalence and characteristics of excessive daytime sleepiness (both groups) and excessive fatigue (PD patients).A high prevalence of sleep disturbances in PD patients was found; this is to a large extent probably the result of aging. As compared with controls, patients had a more severely disturbed sleep maintenance because of nycturia, pain, stiffness, and problems with turning in bed. The prevalence of excessive dreaming is similar in both groups, but altered dream experiences almost exclusively occurred in PD.Patients rated themselves more often to be morning-types than controls. This finding may account for the reported adaptation effects in experimental settings and the reduced REM latency in PD patients.The prevalence of daytime sleepiness was similar in both groups. Excessive daytime sleepiness showed a clear diurnal pattern with a peak in the early afternoon. As for excessive fatigue, the majority of the patients did not report a preferential time for this symptom. Our findings further argue against an association of fatigue with any circadian factor, and instead suggest a relationship with the motor deficits of PD.

Patient-reported autonomic symptoms in Parkinson disease

Objective: There is a wide range of autonomic symptoms (AS) in Parkinson disease (PD), but the full spectrum has never been evaluated with a validated instrument and in comparison with control subjects. In this study a reliable and valid instrument, the SCOPA–AUT, was used to evaluate the occurrence of AS in a large cohort of patients with PD and control subjects and to assess the relations with demographic, disease-related, and clinical variables. Methods: A cohort of 420 patients with PD was evaluated for the occurrence of AS, motor and nonmotor symptoms, as well as for demographic and disease-related characteristics. Results were compared with those of 150 control subjects. Associations between AS and demographic and clinical characteristics were also studied. Results: For all autonomic domains, patients with PD reported more symptoms compared to control subjects, with the greatest differences in the gastrointestinal and urinary domain. Higher age, greater disease severity, and higher doses of dopaminergic medication were related to more autonomic problems. Autonomic symptom severity was associated with more motor dysfunction, depressive symptoms, cognitive dysfunction, psychiatric complications, nighttime sleep disturbances, and excessive daytime sleepiness (all p values < 0.01). Conclusions: Autonomic symptoms (AS) are an important feature of Parkinson disease (PD) and increase with age, disease severity, and medication use. The prominent presence of AS warrants increased clinical awareness and highlights the need for efficacious therapies for the wide spectrum of problems related to this domain of PD.

International study on the psychometric attributes of the Non-Motor Symptoms Scale in Parkinson disease

Background: Nonmotor symptoms (NMS) have a great impact on patients with Parkinson disease (PD). The Non-Motor Symptoms Scale (NMSS) is an instrument specifically designed for the comprehensive assessment of NMS in patients with PD. NMSS psychometric properties have been tested in this study. Methods: Data were collected in 12 centers across 10 countries in America, Asia, and Europe. In addition to the NMSS, the following measures were applied: Scales for Outcomes in Parkinson’s Disease (SCOPA)-Motor, SCOPA-Psychiatric Complications (SCOPA-PC), SCOPA-Cognition, Hoehn and Yahr Staging (HY), Clinical Impression of Severity Index for Parkinson’s Disease (CISI-PD), SCOPA-Autonomic, Parkinson’s Disease Sleep Scale (PDSS), Parkinson’s Disease Questionnaire–39 items (PDQ-39), and EuroQol–5 dimensions (EQ-5D). NMSS acceptability, reliability, validity, and precision were analyzed. Results: Four hundred eleven patients with PD, 61.3% men, were recruited. The mean age was 64.5 ± 9.9 years, and mean disease duration was 8.1 ± 5.7 years. The NMSS score was 57.1 ± 44.0 points. The scale was free of floor or ceiling effects. For domains, the Cronbach α coefficient ranged from 0.44 to 0.85. The intraclass correlation coefficient (0.90 for the total score, 0.67–0.91 for domains) and Lin concordance coefficient (0.88) suggested satisfactory reproducibility. The NMSS total score correlated significantly with SCOPA-Autonomic, PDQ-39, and EQ-5D (rS = 0.57–0.70). Association was close between NMSS domains and the corresponding SCOPA–Autonomic domains (rS = 0.51–0.65) and also with scales measuring related constructs (PDSS, SCOPA-PC) (all p < 0.0001). The NMSS total score was higher for women (p < 0.02) and for increasing disease duration, HY, and CISI-PD severity level (p < 0.001). The SEM was 13.91 for total score and 1.71 to 4.73 for domains. Conclusion: The Non-Motor Symptoms Scale is an acceptable, reproducible, valid, and precise assessment instrument for nonmotor symptoms in Parkinson disease.

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.

Botulinum toxin versus trihexyphenidyl in cervical dystonia A prospective, randomized, double-blind controlled trial

Background: Botulinum toxin type A (BTA) is replacing trihexyphenidyl as the treatment of choice for idiopathic cervical dystonia (ICD), but there has never been a direct comparative study. Methods: This trial compares the effectiveness of BTA with that of trihexyphenidyl in a prospective, randomized, double-blind design. Sixty-six consecutive patients with ICD were randomized to treatment with trihexyphenidyl tablets plus placebo injection or placebo tablets plus BTA injections. Table tswere administered daily according to a fixed schedule. Dysport or saline was injected under EMG guidance at study entry and again after 8 weeks. Patients were assessed for efficacy at baseline and after 12 weeks by different clinical rating scales. Results: Sixty-four patients completed the study, 32 in each group. Mean dose of BTA was 292 mouse units (first session) and 262 mouse units (second session). Mean dose of trihexyphenidyl was 16.25 mg. The changes on the Disability section of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-Disability) (primary outcome), Tsui Scale, and the General Health Perception Subscale were significantly in favor of BTA. More patients treated with BTA had an improvement of at least three points on the TWSTRS-Disability (14 versus 6) and on the Tsui Scale (23 versus 12). Adverse effects were significantly less frequent in the BTA group. Conclusion: BTA is significantly more effective in the treatment of ICD, with less adverse effects. NEUROLOGY 1996;46: 1066-1072

Normal hypocretin-1 levels in Parkinson's disease patients with excessive daytime sleepiness.

Sleep disturbances frequently occur in patients with PD.1 Sleep problems are often related to the disease itself (e.g., difficulties in maintaining sleep because of motor disabilities), but they can also occur secondary to treatment.1 Recently, attention has been focused on so-called “sleep-attacks” in PD, which can be induced by all dopaminomimetic drugs, including D2/3 selective agonists.2 Because the term sleep attack (implicating that the episodes occur without warning) applies only to the minority of episodes, we will use the term “excessive daytime sleepiness” (EDS). EDS induced by dopaminergic treatment in PD shares clinical and neurophysiologic characteristics with EDS seen in narcolepsy.3 Narcolepsy is a sleep disorder clinically characterized by EDS, cataplexy, hypnagogic hallucinations, and sleep paralysis, and is tightly linked to HLA DQB1*0602.4 Narcolepsy is caused by a deficiency in hypocretin neurotransmission (for a review, see Overeem et al.4). Hypocretin-1 and -2 are neuropeptides exclusively produced in the hypothalamus. …

Accelerometric assessment of levodopa-induced dyskinesias in Parkinson's disease.

Our objective was to develop parameters for objective ambulatory measurements of levodopa‐induced dyskinesias (LID) in patients with Parkinsons disease (PD). Twenty‐three PD patients with mild to severe LID were submitted to a standardized protocol of 1‐minute recordings during rest, talking, stress, and four activities of daily life (ADL). Patients were simultaneously monitored with portable multi‐channel accelerometry (four pairs of bi‐axial sensors mounted onto the most affected arm, leg, and at the trunk) and recorded by video. LID severity was assessed with a modified Abnormal Involuntary Movement Scale (m‐AIMS). The signals were analyzed, and every 1/8‐second interval the amplitude was obtained of the dominant frequency within 1–4 Hz and 4–8 Hz frequency bands (Amp1–4 and Amp4–8). For both measures, convergent validity, reproducibility, and responsiveness were determined.