Rianne A. J. Esselink

Unilateral pallidotomy versus bilateral subthalamic nucleus stimulation in PD A randomized trial

Objective: To compare the efficacy of unilateral pallidotomy and bilateral subthalamic nucleus (STN) stimulation in patients with advanced Parkinson disease (PD) in a randomized, observer-blind, multicenter trial. Methods: Thirty-four patients with advanced PD were randomly assigned to have unilateral pallidotomy or bilateral STN stimulation. The primary outcome was the change from baseline to 6 months in the motor part of the Unified PD Rating Scale (motor UPDRS) in the off phase. Secondary outcomes were parkinsonian symptoms in the on phase (motor UPDRS), dyskinesias (Clinical Dyskinesia Rating Scale and dyskinesias UPDRS), functional status (activities of daily living UPDRS and Schwab and England scale), PD Quality of Life questionnaire, changes in drug treatment, and adverse effects. Results: The off phase motor UPDRS score improved from 46.5 to 37 points in the group of pallidotomy patients and from 51.5 to 26.5 in the STN stimulation patients (p = 0.002). Of the secondary outcome measures, on phase motor UPDRS and dyskinesias UPDRS improved significantly in favor of the STN stimulation patients. Reduction of antiparkinsonian drugs was greater after STN stimulation than after pallidotomy. One patient in each group had a major adverse effect. Conclusions: Bilateral STN stimulation is more effective than unilateral pallidotomy in reducing parkinsonian symptoms in patients with advanced 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.

Gait velocity and the Timed-Up-and-Go test were sensitive to changes in mobility in frail elderly patients

OBJECTIVE To estimate clinically relevant changes in functional mobility tests and quantitative gait measures at group and individual level in frail elderly patients. STUDY DESIGN AND SETTING This study was a cohort study of consecutively admitted frail elderly patients. Gait velocity, Timed-Up-and-Go test (TUG), and other mobility tests were measured on admission and 2 weeks later. In between, patients received multidisciplinary treatment. Three experts decided from video recordings if patients had a clinically relevant change in gait, defined as change in the expected risk of falling. RESULTS A total of 85 patients (mean age 75.8 years, 46 female) participated. Of whom, 45% had dementia; 59 patients were stable and 26 showed a clinically relevant change in gait. Gait velocity and TUG were most sensitive to change at group level. In individual patients, a 5% change from baseline in gait velocity and 9% change in TUG had a sensitivity of 92% and 93% for detection of clinically relevant change, but specificity of 27% and 34%, respectively. CONCLUSION At group level, gait velocity and TUG were, from all investigated tests, most sensitive to change and in this perspective the best outcome variables. In individual patients, the high intraindividual variability makes these measures unsuitable as independent screening instruments for clinically relevant changes in gait.

CSF neurofilament light chain and tau differentiate multiple system atrophy from Parkinson's disease

BACKGROUND In early disease stages it can be clinically difficult to differentiate idiopathic Parkinsons disease (IPD) from patients with multiple system atrophy predominated by parkinsonism (MSA-P). METHODS In CSF of 31 patients with IPD, 19 patients with MSA-P, we analyzed tau, neurofilament light chain (NFL) and heavy chain (NFHp35) and the noradrenergic metabolite 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG). RESULTS CSF levels of NFL, NFHp35, and tau were significantly increased in MSA-P (all p<0.0001), whereas, MHPG levels were significantly decreased in MSA-P (p<0.0001). Optimal discriminative cut-off values for the differentiation between MSA-P and IPD were calculated resulting in high sensitivity (76-94%) and specificity (83-97%) levels. Multivariate logistic regression resulted in the combination of NFL and tau as independent contributors in differentiating between MSA-P and IPD. DISCUSSION Higher CSF levels of axonal biomarkers could reflect advanced axonal degeneration in MSA-P. Differentiating MSA-P from IPD could be accurately possible with CSF analysis of a combination of axonal and neurotransmitter biomarkers.

Effects of stereotactic neurosurgery on postural instability and gait in Parkinson's disease.

Postural instability and gait disability (PIGD) are disabling signs of Parkinsons disease. Stereotactic surgery aimed at the internal globus pallidus (GPi) or subthalamic nucleus (STN) might improve PIGD, but the precise effects remain unclear. We performed a systematic review of studies that examined the effects of GPi or STN surgery on PIGD. Most studies examined the effects of bilateral GPi stimulation, bilateral STN stimulation, and unilateral pallidotomy; we, therefore, only performed a meta‐analysis on these studies. Bilateral GPi stimulation, bilateral STN stimulation, and to a lesser extent, unilateral pallidotomy significantly improved PIGD, and more so during the ON phase than during the OFF phase.

CSF α-synuclein does not differentiate between parkinsonian disorders

Differentiating between Parkinsons disease (PD) and atypical Parkinsonism (AP) is clinically relevant but challenging. A timely and correct diagnosis might result in better targeted treatment strategies, adequate patient counseling, and early recognition of disease-specific complications. We aimed to investigate whether cerebrospinal fluid (CSF) concentrations of α-synuclein are of additional diagnostic value. We examined 142 consecutive patients with parkinsonism, mean disease duration 39.7 mo (Parkinsons disease (PD), n = 58; MSA, n = 47; dementia with Lewy bodies (DLB), n = 3; VaP, n = 22; progressive supranuclear palsy (PSP), n = 10; CBD, n = 2). Gold standard was the clinical diagnosis established after 2 years of clinical follow-up. CSF concentrations of α-synuclein, blood pigments and the erythrocyte count were determined. No differences between CSF α-synuclein concentrations of patients with PD with the reference values from our laboratory were observed. We neither found significant differences between patients with PD and AP nor between AP subgroups. Adjustment for age, disease severity or presence of erythrocytes or blood pigments in CSF did not alter these results. Our results imply that CSF α-synuclein is currently unsuitable as biomarker to differentiate between PD and AP.

Frail elderly patients with dementia go too fast

The reason why patients with dementia fall more often and sustain more fractures than patients without dementia remains unclear. Therefore, the relationship between dementia and gait velocity as a marker for mobility and falls in a cohort of frail elderly (mean age of 77.3 years) inpatients was assessed. Patients with dementia were expected to walk slower than patients without dementia. A trend was indeed observed: absolute gait velocity of 0.59 m/s in patients with dementia (n = 63) versus 0.65 m/s in patients without dementia (n = 62; p = 0.19). After adjustment for parkinsonism and walking aids, however, patients with dementia walked 0.44 m/s faster than patients without dementia (p = 0.02). Probable explanations are frontal lobe disinhibition and lack of insight, causing patients with dementia to walk relatively too fast in the context of their frailty. Therefore, the high risk of falls in dementia may be partially explained by the loss of control of gait velocity.

New actigraph for long-term tremor recording

A new method of movement analysis is validated, allowing an actigraph to discriminate tremor from other movements and store duration and intensity measures of both movement types. For algorithm optimization, wrist acceleration was recorded in nine controls and nine Parkinsons disease patients, while simultaneously rating their observed tremor minute by minute on item 20 of the Unified Parkinsons Disease Rating Scale. An optimization procedure to minimize false positives in controls while maximizing tremor detection in patients resulted in false positive tremor classification in 2.4% ± 2.5% of the movement time of control subjects (range, 0%–7%), while providing tremor classification in 82.1% ± 15.4% of the movement time in patients (range, 55%–100%), correlating r = 0.93 with their averaged observed tremor score. A second, generalizability study showed that application of the optimized algorithm resulted in accurate classification of 71% ± 14% of the observed tremor time (range, 46%–90%) in another 9 patients and in a false positive classification in only 0.5% ± 0.8% of the time in another 10 controls (range, 0%–2.4%). The commercial availability of this actigraph now for the first time makes it possible to investigate tremor fluctuations over several weeks. An example is given of how long‐term monitoring can be of use in evaluation of symptom management.

Ten steps to identify atypical parkinsonism

Background: Balance impairment is a frequently encountered problem in patients with Parkinson’s disease. A profound balance disorder, however, is an atypical feature. Methods: Tandem gait performance (10 consecutive tandem steps) was judged in 36 consecutive patients with Parkinson’s disease and 49 consecutive patients with atypical parkinsonism. Results: Only 9 (18%) patients with atypical parkinsonism had a fully normal tandem gait (not a single side step) as opposed to 33 (92%) patients with Parkinson’s disease. Analysis for the subgroup of patients with a disease duration of <3 years yielded the same diagnostic accuracy. Conclusions: Tandem gait performance has a good diagnostic ability to differentiate patients with atypical parkinsonism from those with Parkinson’s disease, and might be used as an additional “red flag” to assist existing clinical tests in identifying atypical parkinsonism.

Morbidity and mortality following pallidotomy in Parkinson’s disease A systematic review

ObjectiveTo study the frequency of morbidity and mortality associated with pallidotomy. MethodThe authors searched the MEDLINE electronic database for pallidotomy articles reported between January 1992 and December 2000. They selected studies by the following criteria: original clinical data, unequivocal description of morbidity and mortality, and unselected consecutive cases. The authors extracted the following data: number of patients, unilateral or bilateral procedures, age, localization technique, follow-up time, number of patients with adverse effects, number of patients with permanent adverse effects (>3 months), types of adverse effects, and mortality. ResultsFor unilateral pallidotomy, 12 prospective studies included 334 patients. Of these patients, 30.2% (95% CI, 25.3 to 35.2) had adverse effects, and 13.8% (95% CI, 10.1 to 17.5) had permanent adverse effects. A symptomatic infarction or hemorrhage occurred in 3.9% (95% CI, 2.1 to 6.6). The mortality rate was 1.2% (95% CI, 0.3 to 3.0). In the series with microelectrode recording, the frequency of adverse effects was 14.4% (95% CI, 4.7 to 24.1) higher and the frequency of stroke was 4.9% (95% CI, 1.4 to 8.4) higher. The most frequent adverse effects were problems with speech (11.1%) and facial paresis (8.4%). For bilateral pallidotomy, five historical cohort studies including 20 patients were available for review. Fourteen patients had an adverse effect, and the most frequent adverse effects were impairments of speech and cognition. ConclusionsThe risk of permanent adverse effects associated with unilateral pallidotomy was 13.8%. A symptomatic infarction or hemorrhage occurred in 3.9% of patients, and the associated mortality rate was 1.2%.