Efficacy of Parenteral Amantadine Therapy in the Treatment of Multiple System Atrophy With Predominant Parkinsonism.

OBJECTIVE: The aim of this study was to assess clinical response to a high-dose intravenous (IV) amantadine given for 5 consecutive days in patients with multiple system atrophy parkinsonism (MSA-P). METHODS: Subjects with a diagnosis of MSA-P treated with IV amantadine were included. Patients' disease severity before and after therapy was evaluated using the Unified Multiple System Atrophy Rating Scale (UMSARS). RESULTS: Fourteen subjects (8 females) were included. In 10 subjects (71.4%), clinical improvement was noted. The UMSARS score after treatment decreased by 2 points (median [interquartile range, 0-3]) when compared with UMSARS score at baseline (P = 0.0020). Upon examining the walking parameter, a trend of improvement was shown (P = 0.0625) (range, 0-1 points). Neither specific demographic parameters nor occurrence of adverse effects was found to be a predictive factor for improvement. Adverse events were mild and transient except for one patient who experienced acute psychosis prompting treatment cessation, upon which psychosis resolved. CONCLUSIONS: Our preliminary data show that IV amantadine may be a safe and effective therapy in MSA-P. A double-blind placebo-controlled trial is needed to establish the true benefit of amantadine therapy.

MRI Guided Focused Ultrasound Thalamotomy for Moderate-to-Severe Tremor in Parkinson's Disease.

Background. Thalamotomy is effective in alleviating tremor in Parkinson's disease (PD). Methods. Seven PD patients, mean age 59.4 ± 9.8 years (range, 46-74) with a mean disease duration of 5.4 ± 2.8 years (range, 2-10) suffering from severe refractory tremor, underwent ventral intermediate nucleus thalamotomy using MRI guided focused ultrasound (MRgFUS), an innovative technology that enables noninvasive surgery. Results. Tremor stopped in the contralateral upper extremity in all patients immediately following treatment. Total UPDRS decreased from 37.4 ± 12.2 to 18.8 ± 11.1 (p = 0.007) and PDQ-39 decreased from 42.3 ± 16.4 to 21.6 ± 10.8 (p = 0.008) following MRgFUS. These effects were sustained (mean follow-up 7.3 months). Adverse events during MRgFUS included headache (n = 3), dizziness (n = 2), vertigo (n = 4), and lip paresthesia (n = 1) and following MRgFUS were hypogeusia (n = 1), unsteady feeling when walking (n = 1, resolved), and disturbance when walking tandem (n = 1, resolved). Conclusions. Thalamotomy using MRgFUS is safe and effective in PD patients. Large randomized studies are needed to assess prolonged efficacy and safety.

Relaxation guided imagery reduces motor fluctuations in Parkinson's disease.

BACKGROUND: Motor fluctuations in Parkinson's disease (PD) cause major disabling symptoms. OBJECTIVE: We aimed to assess the efficacy of relaxation guided imagery in PD patients with motor fluctuation. METHODS: In a prospective pilot, case cohort, PD patients underwent (i) a relaxation session with relaxation guided imagery, and (ii) a control session of relaxing music. Three-day diaries were completed at baseline and after each intervention. Subsequently, patients received discs for home listening-a relaxation guided imagery disc and a relaxing music disc. After three months the patients were interviewed by phone. RESULTS: Twenty one PD patients participated and 19 completed this study. There was a significant increase in the percent of "on" time after listening to the relaxation guided imagery disc as compared with baseline (from 47.7% to 62.8%, 95% CI 5.26-25.03, p = 0.005). Relaxing music caused no significant change in percent of "on" time from baseline (from 47.7% to 53.0%, p = 0.161). Although all sessions were performed in "on" state, there was a significant decrease in UPDRS motor subscores after each of the two sessions as compared with the UPDRS score before the session (relaxation guided imagery mean reduction -3.81 p = 0.0002 and after relaxing music mean reduction -1.95, p = 0.001), significantly more so after the relaxation guided imagery (p = 0.020). After 3 months listening to the relaxation guided imagery disc increased "on" time from baseline by 12.6% (95% CI 3.19-28.39, p = 0.111) but this did not reach statistical significance. CONCLUSION: In this pilot study we showed that relaxation guided imagery is a promising treatment for PD.

Handwriting as an objective tool for Parkinson's disease diagnosis.

To date, clinical assessment remains the gold standard in the diagnosis of Parkinson's disease (PD). We sought to identify simple characteristics of handwriting which could accurately differentiate PD patients from healthy controls. Twenty PD patients and 20 matched controls wrote their name and copied an address on a paper affixed to a digitizer. Mean pressure and mean velocity was measured for the entire task and the spatial and temporal characteristics were measured for each stroke. Results of the MANOVAs for the temporal, spatial, and pressure measures (stroke length, width, and height; mean pressure; mean time per stroke; mean velocity), for both the name writing and address copying tasks, showed significant group effects (F(6,32) = 6.72, p < 0.001; F(6,31) = 14.77, p < 0.001, respectively). A discriminant analysis was performed for the two tasks. One discriminant function was found for the group classification of all participants (Wilks' Lambda = 0.305, p < 0.001). Based on this function, 97.5% of participants were correctly classified (100% of the controls and 95% of PD patients). A Kappa value of 0.947 (p < 0.001) was calculated, demonstrating that the group classification did not occur by chance. In this pilot study we identified two simple short and routine writing tasks which differentiate PD patients from healthy controls. These writing tasks have future potential as cost-effective, fast and reliable biomarkers for PD.

Parkinson's disease tremor is diminished with relaxation guided imagery.

Patients with Parkinson's disease (PD) may have pronounced tremor that exacerbates during stress. To determine whether PD tremor improves with relaxation guided imagery (RGI) and relaxing music. Twenty patients with PD with moderate to severe tremor participated in sessions where relaxation techniques were implemented. Tremor was objectively monitored using an accelerometer. RGI dramatically decreased tremor in all 20 patients (baseline 270.38 +/- 85.82 vs. RGI 35.57 +/- 43.90 movements per minute P < 0.0001). In 15 patients, RGI completely abolished tremor for 1-13 min. Average tremor activity remained significantly below baseline both 15 min and 30 min after RGI was discontinued (P < 0.001). Patients reported improvement lasting 2-14 hours (mean 6.8 +/- 3.8). Relaxing music significantly reduced tremor but to a lesser degree than RGI (220.04 +/- 106.53 movements per minute P = 0.01). Self-relaxation had no significant effect on tremor. RGI can supplement conventional medical treatments for tremor in patients with PD on best medical treatment.

Cardiovascular risk factors in restless legs syndrome.

We conducted a population-based cross-sectional study to assess prevalence of cardiovascular risk factors in subjects with and without restless legs syndrome (RLS). Adults attending their annual checkup completed the International RLS Study Group questionnaire and underwent an interview by a neurologist. Data from the annual checkup were compared between subjects with and without RLS. The prevalence of RLS was 6.7% (95% CI 5.45-7.95) among 1,537 responders. RLS subjects' blood tests showed significantly higher fasting blood glucose level (P = 0.029), higher prevalence of hypercholesterolemia (P = 0.029) and reduced renal function (P = 0.013), and increased prevalence of low hematocrit (P = 0.008). RLS subjects weighed more (P = 0.029), had a higher BMI (P = 0.033), larger hip circumference (P = 0.033), and were less fit (P = 0.010). To control for interactions among statistical predictors, we also employed multivariate logistic regression models adjusted for age, gender, smoking, BMI, hemoglobin, glucose, HDL/LDL cholesterol, triglycerides, and creatinine. We found that female gender (OR 2.16; 95% CI 1.11-4.17), smoking (OR 1.82; 95% CI, 1.10-3.00), and HDL/LDL cholesterol (OR 0.18; 95% CI 0.034-0.90) were significantly associated with RLS compared with subjects without RLS. RLS was associated with cardiovascular risk factors.

Paradoxical kinesia at war.

Paradoxical kinesia is the sudden transient ability of a patient with Parkinson's disease to perform a task he was previously unable to perform, usually when facing an immediate threat. The sensory cues governing this behavior and the prevalence in real life situations are unknown. The objective of this study was to determine the occurrence of paradoxical kinesia in Parkinson's disease (PD) patients whose residential area was suddenly a war zone, under a life threatening missile attack, necessitating immediate evacuation. Fifty PD patients were interviewed during and immediately following the war. Only two patients experienced paradoxical kinesia, one war related and the other historical, both in response to visual cues. In contrast, an auditory stimulus in the form of a frightening loud siren, warning patients of an imminent missile attack, did not induce paradoxical kinesia. When questioned about their general function during wartime, patients reported significant increases in OFF time (P < 0.01), dyskinesia (P < 0.009), anxiety (P < 0.002), and depression (P < 0.01) as compared with their performance before the war. Paradoxical kinesia is uncommon, even in the face of danger. Visual, but not auditory, triggers appear to be needed to prompt its occurrence.