Search

Background The long-term impact of deep brain stimulation (DBS) on Parkinson's disease (PD) is difficult to assess and has not yet been rigorously evaluated in comparison to its natural history. Objective Comparison of key disability milestones (recurrent falls, psychosis, dementia, and institutionalization) and death in patients with PD with versus without DBS. Methods We collected retrospective information from clinical notes of patients with PD at our center that were implanted with subthalamic DBS >8 years ago (1999-2010) and a control group of PD patients without DBS similar in age at onset, age at baseline, sex distribution, and number of comorbidities at baseline (extracted from a registry study performed in 2004). Cox regression models were used to calculate hazard ratios, adjusted for potential baseline confounding variables (age, sex, disease duration, disease severity, and number of comorbidities). Results A total of 74 DBS-treated and 61 control patients with PD were included. For a median observational period of 14 years, patients treated with DBS were at lower risk of experiencing recurrent falls (hazard ratio = 0.57; 95% confidence interval, 0.37-0.90; P = 0.015) and psychosis (hazard ratio = 0.26; 95% confidence interval, 0.12-0.59; P = 0.001) compared with control patients. There was no significant difference in risk for dementia, institutionalization, or death. Disease progression as assessed by Hoehn and Yahr scores was not slower in DBS-treated patients. Conclusions Treatment with chronic subthalamic DBS was associated with lower risk for recurrent falls and psychotic symptoms, effects that may be mediated through improved motor symptom control and reduction in dopaminergic therapies, respectively. There was no evidence for DBS effects on underlying disease progression.

Background Putaminal diffusivity in brain magnetic resonance diffusion-weighted imaging (DWI) is increased in patients with the parkinsonian variant of multiple system atrophy (MSA-P) compared to Parkinson disease (PD) patients. Purpose We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of DWI to distinguish MSA-P from PD. Methods Studies on DWI were identified through a systematic PubMed and Clarivate Analytics® Web of Science® Core Collection search. Papers were selected based on stringent inclusion criteria; minimum requirement was the inclusion of MSA-P and PD patients and documented true positive, true negative, false positive and false negative rates or overall sample size and reported sensitivity and specificity. Meta-analysis was performed using the hierarchical summary receiver operating characteristics curve approach. Results The database search yielded 1678 results of which 9 studies were deemed relevant. Diagnostic accuracy of putaminal diffusivity measurements were reported in all of these 9 studies, whereas results of other regions of interest were only reported irregularly. Therefore, a meta-analysis could only be performed for putaminal diffusivity measurements: 127 patients with MSA-P, 262 patients with PD and 70 healthy controls were included in the quantitative synthesis. The meta-analysis showed an overall sensitivity of 90% (95% confidence interval (CI): 76.7%-95.8%) and an overall specificity of 93% (95% CI: 80.0%-97.7%) to distinguish MSA-P from PD based on putaminal diffusivity. Conclusion Putaminal diffusivity yields high sensitivity and specificity to distinguish clinically diagnosed patients with MSA-P from PD. The confidence intervals indicate substantial variability. Further multicenter studies with harmonized protocols are warranted particularly in early disease stages when clinical diagnosis is less certain.

Background and objective There is limited evidence about the efficacy and safety of cannabinoids in the treatment of patients with Huntington’s disease (HD). Five patients with HD were treated with nabilone, a synthetic cannabinoid, in order to alleviate therapy-resistant symptoms. Methods All patients and caregivers were informed about the off-label use of nabilone and gave written informed consent. A Clinical Global Impression Scale (CGI) and the Unified Huntington9s Disease Rating Scale (UHDRS) were applied prior, after one and four weeks to decide on the continuation of nabilone treatment. Case reports Patient 1 is a 20-year-old male who presented with disabling tics, generalised chorea and increased irritability. He developed severe parkinsonism during therapy with amisulpiride and olanzapine. Amisulpiride was stopped and he was treated with nabilone 1 mg/d. Patient 2 is a 48-year-old female with 10 years history of HD and chronic pain. Multiple treatment trials were ineffective. Nabilone 2 mg/d was introduced. Patient 3 is a 62-year-old female with disabling chorea and increased irritability. She developed severe akathisia as a side effect of several antidopaminergic therapies. Treatment with nabilone 1.5 mg/d was commenced. Patient 4 is a 46-year-old female who had parkinsonism and depression under therapy with tetrabenazine. Treatment with nabilone 3 mg/d was introduced as monotherapy. Patient 5 is a 67-year-old female with disabling chorea and increased irritability. She developed parkinsonism during therapy with tetrabenazine. Medication was changed to 2 mg/d nabilone. Results Transient mild sedation during titration occurred in patients 3, 4 and 5, mild non-disturbing xerostomia in patient 3. All patients reported improved symptoms as assessed by the CGI. UHDRS and Chorea-scores improved in all patients. A reduction of tics without worsening of parkinsonism with nabilone was seen in patient 1. Patient 2 reported that her pain completely subsided. Irritability substantially improved with nabilone in patients 1, 3 and 5. Moreover, tetrabenazine could be stopped in patients 3, 4 and 5. This resulted in a remission of akathisia in patient 3, in improved parkinsonism in patients 4 and 5 as well as in ameliorated mood in patient 4. Conclusions These case series suggest that nabilone may be an effective and well tolerated adjunct to the drug treatment of HD. However, larger controlled trials are needed to confirm these preliminary open-label observations.

Contains fulltext : 287484.pdf (Publisher’s version ) (Open Access) BACKGROUND: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear. METHODS: We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome. RESULTS: A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P