Development and Validation of the Dystonia-Pain Classification System: A Multicenter Study.

BACKGROUND: Dystonia is associated with disabling nonmotor symptoms like chronic pain (CP), which is prevalent in dystonia and significantly impacts the quality of life (QoL). There is no validated tool for assessing CP in dystonia, which substantially hampers pain management. OBJECTIVE: The aim was to develop a CP classification and scoring system for dystonia. METHODS: A multidisciplinary group was established to develop the Dystonia-Pain Classification System (Dystonia-PCS). The classification of CP as related or unrelated to dystonia was followed by the assessment of pain severity score, encompassing pain intensity, frequency, and impact on daily living. Then, consecutive patients with inherited/idiopathic dystonia of different spatial distribution were recruited in a cross-sectional multicenter validation study. Dystonia-PCS was compared to validated pain, mood, QoL, and dystonia scales (Brief Pain Inventory, Douleur Neuropathique-4 questionnaire, European QoL-5 Dimensions-3 Level Version, and Burke-Fahn-Marsden Dystonia Rating Scale). RESULTS: CP was present in 81 of 123 recruited patients, being directly related to dystonia in 82.7%, aggravated by dystonia in 8.8%, and nonrelated to dystonia in 7.5%. Dystonia-PCS had excellent intra-rater (Intraclass Correlation Coefficient - ICC: 0.941) and inter-rater (ICC: 0.867) reliability. In addition, pain severity score correlated with European QoL-5 Dimensions-3 Level Version's pain subscore (r = 0.635, P < 0.001) and the Brief Pain Inventory's severity and interference scores (r = 0.553, P < 0.001 and r = 0.609, P < 0.001, respectively). CONCLUSIONS: Dystonia-PCS is a reliable tool to categorize and quantify CP impact in dystonia and will help improve clinical trial design and management of CP in patients affected by this disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Spinal cord stimulation improves gait in patients with Parkinson's disease previously treated with deep brain stimulation.

BACKGROUND: Deep brain stimulation and levodopatherapy ameliorate motor manifestations in Parkinson's disease, but their effects on axial signs are not sustained in the long term. OBJECTIVES: The objective of this study was to investigate the safety and efficacy of spinal cord stimulation on gait disturbance in advanced Parkinson's disease. METHODS: A total of 4 Parkinson's disease patients who experienced significant postural instability and gait disturbance years after chronic subthalamic stimulation were treated with spinal cord stimulation at 300 Hz. Timed-Up-GO and 20-meter-walk tests, UPDRS III, freezing of gait questionnaire, and quality-of-life scores were measured at 6 months and compared to baseline values. Blinded assessments to measure performance in the Timed-Up-GO and 20-meter-walk tests were carried out during sham stimulation at 300 Hz and 60 Hz. RESULTS: Patients treated with spinal cord stimulation had approximately 50% to 65% improvement in gait measurements and 35% to 45% in UPDRS III and quality-of-life scores. During blinded evaluations, significant improvements in the Timed-Up-GO and 20-meter-walk tests were only recorded at 300 Hz. CONCLUSION: Spinal cord stimulation at 300 Hz was well tolerated and led to a significant improvement in gait. © 2016 International Parkinson and Movement Disorder Society.

Metabolic and Structural Signatures of Speech and Language Impairment in Corticobasal Syndrome: A Multimodal PET/MRI Study.

Introduction: Corticobasal syndrome (CBS) is a progressive neurological disorder related to multiple underlying pathologies, including four-repeat tauopathies, such as corticobasal degeneration and progressive supranuclear palsy, and Alzheimer's disease (AD). Speech and language are commonly impaired, encompassing a broad spectrum of deficits. We aimed to investigate CBS speech and language impairment patterns in light of a multimodal imaging approach. Materials and Methods: Thirty-one patients with probable CBS were prospectively evaluated concerning their speech-language, cognitive, and motor profiles. They underwent positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET) and [11C]Pittsburgh Compound-B (PIB-PET) on a hybrid PET-MRI machine to assess their amyloid status. PIB-PET images were classified based on visual and semi-quantitative analyses. Quantitative group analyses were performed on FDG-PET data, and atrophy patterns on MRI were investigated using voxel-based morphometry (VBM). Thirty healthy participants were recruited as imaging controls. Results: Aphasia was the second most prominent cognitive impairment, presented in 67.7% of the cases, following apraxia (96.8%). We identified a wide linguistic profile, ranging from nonfluent variant-primary progressive aphasia to lexical-semantic deficits, mostly with impaired verbal fluency. PIB-PET was classified as negative (CBS-A- group) in 18/31 (58%) and positive (CBS-A+ group) in 13/31 (42%) patients. The frequency of dysarthria was significantly higher in the CBS-A- group than in the CBS-A+ group (55.6 vs. 7.7%, p = 0.008). CBS patients with dysarthria had a left-sided hypometabolism at frontal regions, with a major cluster at the left inferior frontal gyrus and premotor cortex. They showed brain atrophy mainly at the opercular frontal gyrus and putamen. There was a positive correlation between [18F]FDG uptake and semantic verbal fluency at the left inferior (p = 0.006, R 2 = 0.2326), middle (0.0054, R 2 = 0.2376), and superior temporal gyri (p = 0.0066, R 2 = 0.2276). Relative to the phonemic verbal fluency, we found a positive correlation at the left frontal opercular gyrus (p = 0.0003, R 2 = 0.3685), the inferior (p = 0.0004, R 2 = 0.3537), and the middle temporal gyri (p = 0.0001, R 2 = 0.3993). Discussion: In the spectrum of language impairment profile, dysarthria might be helpful to distinguish CBS patients not related to AD. Metabolic and structural signatures depicted from this feature provide further insights into the motor speech production network and are also helpful to differentiate CBS variants.

Little Brain, Big Expectations.

The cerebellum has been implicated in the mechanisms of several movement disorders. With the recent reports of successful modulation of its functioning, this highly connected structure has emerged as a promising way to provide symptomatic relief not yet obtained by usual treatments. Here we review the most relevant papers published to date, the limitations and gaps in literature, discuss why several papers have failed in showing efficacy, and present a new way of stimulating the cerebellum. References for this critique review were identified by searches on PubMed for the terms "Parkinson's disease", "ataxia", "dystonia", "tremor", and "dyskinesias" in combination with the type of stimulation and the stimulation site. Studies conducted thus far have shed light on the potential of cerebellar neuromodulation for attenuating symptoms in patients with some forms of isolated and combined dystonia, dyskinesia in Parkinson's disease, and neurodegenerative ataxia. However, there is still a high heterogeneity of results and uncertainty about the possibility of maintaining long-term benefits. Because of the complicated architecture of the cerebellum, the modulation techniques employed may have to focus on targeting the activity of the cerebellar nuclei rather than the cerebellar cortex. Measures of cerebellar activity may reduce the variability in outcomes.

Association between Parkinson's disease and glucocerebrosidase mutations in Brazil.

OBJECTIVE: To evaluate the association between parkinsonism and mutations in the glucocerebrosidase gene (GBA) in Brazilian patients. METHODS: We searched for three GBA common mutations (N370S, L444P and G377S) in 65 Brazilian patients affected by PD with disease onset before the age of 55 and compared the results to 267 age- and sex-matched controls. RESULTS: GBA mutations were detected at a significantly higher frequency among Parkinson's disease patients (2/65=3%), when compared to the control group (0/267): P=0.0379. CONCLUSION: These results provide further evidence for GBA mutations being a possible hereditary risk factor for PD.

rTMS treatment for depression in Parkinson's disease increases BOLD responses in the left prefrontal cortex.

The mechanisms underlying the effects of antidepressant treatment in patients with Parkinson's disease (PD) are unclear. The neural changes after successful therapy investigated by neuroimaging methods can give insights into the mechanisms of action related to a specific treatment choice. To study the mechanisms of neural modulation of repetitive transcranial magnetic stimulation (rTMS) and fluoxetine, 21 PD depressed patients were randomized into only two active treatment groups for 4 wk: active rTMS over left dorsolateral prefrontal cortex (DLPFC) (5 Hz rTMS; 120% motor threshold) with placebo pill and sham rTMS with fluoxetine 20 mg/d. Event-related functional magnetic resonance imaging (fMRI) with emotional stimuli was performed before and after treatment - in two sessions (test and re-test) at each time-point. The two groups of treatment had a significant, similar mood improvement. After rTMS treatment, there were brain activity decreases in left fusiform gyrus, cerebellum and right DLPFC and brain activity increases in left DLPFC and anterior cingulate gyrus compared to baseline. In contrast, after fluoxetine treatment, there were brain activity increases in right premotor and right medial prefrontal cortex. There was a significant interaction effect between groups vs. time in the left medial prefrontal cortex, suggesting that the activity in this area changed differently in the two treatment groups. Our findings show that antidepressant effects of rTMS and fluoxetine in PD are associated with changes in different areas of the depression-related neural network.

Pseudoathetosis: report of three patients.

We report on 3 patients with pseudoathetosis, which are involuntary, slow, writhing movements due to loss of proprioception.