Eugene C. Lai

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.

Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease

BACKGROUND Deep-brain stimulation is the surgical procedure of choice for patients with advanced Parkinsons disease. The globus pallidus interna and the subthalamic nucleus are accepted targets for this procedure. We compared 24-month outcomes for patients who had undergone bilateral stimulation of the globus pallidus interna (pallidal stimulation) or subthalamic nucleus (subthalamic stimulation). METHODS At seven Veterans Affairs and six university hospitals, we randomly assigned 299 patients with idiopathic Parkinsons disease to undergo either pallidal stimulation (152 patients) or subthalamic stimulation (147 patients). The primary outcome was the change in motor function, as blindly assessed on the Unified Parkinsons Disease Rating Scale, part III (UPDRS-III), while patients were receiving stimulation but not receiving antiparkinsonian medication. Secondary outcomes included self-reported function, quality of life, neurocognitive function, and adverse events. RESULTS Mean changes in the primary outcome did not differ significantly between the two study groups (P=0.50). There was also no significant difference in self-reported function. Patients undergoing subthalamic stimulation required a lower dose of dopaminergic agents than did those undergoing pallidal stimulation (P=0.02). One component of processing speed (visuomotor) declined more after subthalamic stimulation than after pallidal stimulation (P=0.03). The level of depression worsened after subthalamic stimulation and improved after pallidal stimulation (P=0.02). Serious adverse events occurred in 51% of patients undergoing pallidal stimulation and in 56% of those undergoing subthalamic stimulation, with no significant between-group differences at 24 months. CONCLUSIONS Patients with Parkinsons disease had similar improvement in motor function after either pallidal or subthalamic stimulation. Nonmotor factors may reasonably be included in the selection of surgical target for deep-brain stimulation. (ClinicalTrials.gov numbers, NCT00056563 and NCT01076452.)

Randomized trial of deep brain stimulation for Parkinson disease: Thirty-six-month outcomes

Objectives: Our objective was to compare long-term outcomes of deep brain stimulation (DBS) of the globus pallidus interna (GPi) and subthalamic nucleus (STN) for patients with Parkinson disease (PD) in a multicenter randomized controlled trial. Methods: Patients randomly assigned to GPi (n = 89) or STN DBS (n = 70) were followed for 36 months. The primary outcome was motor function on stimulation/off medication using the Unified Parkinsons Disease Rating Scale motor subscale. Secondary outcomes included quality of life and neurocognitive function. Results: Motor function improved between baseline and 36 months for GPi (41.1 to 27.1; 95% confidence interval [CI] −16.4 to −10.8; p < 0.001) and STN (42.5 to 29.7; 95% CI −15.8 to −9.4; p < 0.001); improvements were similar between targets and stable over time (p = 0.59). Health-related quality of life improved at 6 months on all subscales (all p values significant), but improvement diminished over time. Mattis Dementia Rating Scale scores declined faster for STN than GPi patients (p = 0.01); other neurocognitive measures showed gradual decline overall. Conclusions: The beneficial effect of DBS on motor function was stable and comparable by target over 36 months. Slight declines in quality of life following initial gains and gradual decline in neurocognitive function likely reflect underlying disease progression and highlight the importance of nonmotor symptoms in determining quality of life. Classification of Evidence: This study provides Class III evidence that improvement of motor symptoms of PD by DBS remains stable over 3 years and does not differ by surgical target. Neurology® 2012;79:55–65

Peripherally induced oromandibular dystonia

OBJECTIVES Oromandibular dystonia (OMD) is a focal dystonia manifested by involuntary muscle contractions producing repetitive, patterned mouth, jaw, and tongue movements. Dystonia is usually idiopathic (primary), but in some cases it follows peripheral injury. Peripherally induced cervical and limb dystonia is well recognised, and the aim of this study was to characterise peripherally induced OMD. METHODS The following inclusion criteria were used for peripherally induced OMD: (1) the onset of the dystonia was within a few days or months (up to 1 year) after the injury; (2) the trauma was well documented by the patient’s history or a review of their medical and dental records; and (3) the onset of dystonia was anatomically related to the site of injury (facial and oral). RESULTS Twenty seven patients were identified in the database with OMD, temporally and anatomically related to prior injury or surgery. No additional precipitant other than trauma could be detected. None of the patients had any litigation pending. The mean age at onset was 50.11 (SD 14.15) (range 23–74) years and there was a 2:1 female preponderance. Mean latency between the initial trauma and the onset of OMD was 65 days (range 1 day-1 year). Ten (37%) patients had some evidence of predisposing factors such as family history of movement disorders, prior exposure to neuroleptic drugs, and associated dystonia affecting other regions or essential tremor. When compared with 21 patients with primary OMD, there was no difference for age at onset, female preponderance, and phenomenology. The frequency of dystonic writer’s cramp, spasmodic dysphonia, bruxism, essential tremor, and family history of movement disorder, however, was lower in the post-traumatic group (p<0.05). In both groups the response to botulinum toxin treatment was superior to medical therapy (p<0.005). Surgical intervention for temporomandibular disorders was more frequent in the post-traumatic group and was associated with worsening of dystonia. CONCLUSION The study indicates that oromandibular-facial trauma, including dental procedures, may precipitate the onset of OMD, especially in predisposed people. Prompt recognition and treatment may prevent further complications.

The ALSSQOL: balancing physical and nonphysical factors in assessing quality of life in ALS.

Background: There is no generally accepted instrument for measuring quality of life (QOL) in patients with ALS. Current instruments are either too heavily weighted toward strength and physical function or useful for the evaluation of individuals but of less utility in assessing large samples. Objective: To develop and evaluate the psychometric properties of an ALS-specific QOL instrument (the ALSSQOL) that would reflect overall QOL as assessed by the patient and would be valid and reliable across large samples. Methods: The ALSSQOL is based on the McGill Quality of Life Questionnaire (MQOL), modified by changes in format and by adding questions on religiousness and spirituality, items derived from interviews with ALS patients, and items identified from open-ended questions administered during the MQOL. The psychometric properties of the ALSSQOL were assessed by a prospective multicenter study in which participants completed the ALSSQOL, other instruments measuring overall QOL, and instruments assessing religiousness, spirituality, and psychological distress. Results: A 59-item ALSSQOL was developed; 342 patients evaluated its psychometric properties. Completion time averaged 15 minutes. Forty-six items loaded on six factors. The ALSSQOL demonstrated concurrent, convergent, and discriminant validity for the overall instrument and convergent validity for its subscales. Analysis of individual items permitted insight into variables of clinical importance. Conclusions: This new ALS-specific quality of life instrument is a practical tool for the assessment of overall quality of life in individuals with ALS and appears to be valid and useful across large samples. Validation studies of a shortened version are now under way.

Long-term efficacy of posteroventral pallidotomy in the treatment of Parkinson’s disease

Article abstract The authors describe results of unilateral posteroventral pallidotomy (PVP) in 89 patients with PD. At 3 months after surgery, 81.9% of the patients reported marked or moderate improvement in their parkinsonian symptoms. Postoperative Unified PD Rating Scale “off” state mean total motor score improved by 35.5% and the mean activities of daily living score by 33.7% (p < 0.001). Improvements in parkinsonian symptoms were maintained in both “off” and “on” states in 62 patients at 12 months after PVP and in 41 patients who were followed for 18 months or longer (mean 26.6 months).

Movement and reaction times and fine coordination tasks following pallidotomy

The effect of a unilateral, microelectrode‐guided lesion in the globus pallidum internum (GPi) was evaluated in 41 patients (21 women) with moderately advanced Parkinsons disease (PD). The mean age was 60.3 ± 9.0 years (range, 40–74) and the mean symptom duration was 14.7 ± 5.3 years (range, 4–25). In addition to clinical ratings, movement time (MT) and reaction time (RT) tests were performed at baseline and 3 months after surgery during the “practically defined off” state (more than 12 hours after the last dose of levodopa). Improvement occurred bilaterally with more robust and statistically significant improvement on the contralateral side in all RT tests. Simple reaction time (SRT) improved by 14.5% (p < 0.001) and the choice reaction time (CRT) by 12.2% (p < 0.001) when the arm contralateral to the pallidotomy side was tested. There was a trend toward improvement in the ipsilateral arm. The MT, determined by repetitive movement between two adjacent targets, improved by 24% contralaterally (p < 0.0001) and by 12% ipsilaterally (p < 0.005). In addition, the Purdue Pegboard (PP) test scores, used to evaluate hand dexterity, improved on the contralateral side by 35.5% (p < 0.0002) but there was no statistically significant ipsilateral improvement. To the extent that MT and RT are quantitative measures of bradykinesia, our study provides evidence that this parkinsonian feature improves after pallidotomy.

Daily energy expenditure, physical activity, and weight loss in Parkinson's disease patients.

Patients with Parkinsons disease (PD) commonly exhibit weight loss (WL) which investigators attribute to various factors, including elevated energy expenditure. We tested the hypothesis that daily energy expenditure (DEE) and its components, resting energy expenditure (REE) and physical activity (PA) energy expenditure (PAEE), are elevated in WL compared with weight stable (WS) PD patients. We measured DEE in 10 PD WL patients and 10 PD WS patients using doubly labeled water (DLW). PAEE was estimated with DLW, activity monitors, and activity questionnaires. REE was measured with indirect calorimetry. We evaluated energy intake (EI) with a patients 3‐day food diary. Data was assessed employing SPSS, Spearman correlation coefficients, and Bland and Altman plots. There was no difference in DEE between the WL and WS groups measured with DLW. There were no differences in REE and EI between groups. DEE (r = 0.548, P < 0.05) and PAEE (r = 0.563, P < 0.01) are related with caloric intake. The WL group had higher PA than the WS group (P < 0.042) only when measured with wrist activity monitors. Results suggest that WL in PD patients cannot be fully explained by an increase in DEE. Large longitudinal studies to examine multiple relationships between variables might provide us with a better understanding of WL among PD patients.

Proxy reports in Parkinson's disease: caregiver and patient self-reports of quality of life and physical activity.

We evaluated patient–proxy agreement in a population of veterans with Parkinsons disease and compared levels of agreement by patient subgroups. Patient and caregiver pairs completed questionnaires composed of standard measures and additional demographic and activity questions. Participants completed the Center for Epidemiologic Studies Depression Scale (CES‐D), the PD Questionnaire 39 (PDQ‐39), and three questions regarding physical activity. Caregivers completed proxy forms of the PDQ‐39 and the physical activity questionnaire. The proxy forms asked caregivers to choose the answers that best described their “friends/patients situation.” The results of our comparison of patient and proxy reports of quality of life were consistent with findings in other diseases. On average, proxies rated patient disability higher and quality of life lower than did patients. However, our comparison of patient and proxy reports of frequency of exercise diverged from previously published work. Less agreement was observed between patient and proxy reports of physical activity, even though this is a more objective variable than are the domains measured by the PDQ‐39. Proxy reports may diverge appreciably from patient self‐reports. These differences should be considered in research design and clinical decision making. Alternative approaches to the measurement of patient relevant outcomes could supplement traditional, retrospective self‐reports.

Neuropsychological outcome after unilateral pallidotomy for the treatment of Parkinson's disease

OBJECTIVE To assess the long term cognitive outcome of unilateral posteroventral pallidotomy (PVP) and the overall efficacy of the surgery. METHODS Forty two (29 left and 13 right PVP) patients with Parkinsons disease underwent neurological and neuropsychological testing before PVP and at 3 and 12 months after PVP. The neuropsychological testing battery emphasised measures of verbal learning and memory, visuospatial abilities, speed of information processing, executive functioning, and affective functioning. RESULTS All patients demonstrated motor improvements after surgery during their off state, and 86% of patients also showed improvements in motor functioning in their on state. Repeated measures ANOVA showed significant improvements in confrontational naming, visuospatial organisation, and affective functioning 3 months and 12 months after surgery, with inconsistent improvements in executive functioning 12 months post-PVP. Patients demonstrated a transient impairment in verbal memory, with verbal learning performance returning to baseline 12 months post-PVP after a significant decline 3 months after PVP. When three patients with lesions extending outside of the PVP were excluded from the analysis, a decline in verbal fluency performance after PVP was not found to be significant. Differences due to side of lesion placement were not found on any of the cognitive measures. CONCLUSIONS In the largest long term follow up study reported to date, the cognitive changes found up to a year after PVP are minimal compared with the robust improvements in motor function. The findings highlight the need to investigate the relation between the specific fibre tracts affected by the lesions and cognitive outcome.