A Double-Blind, Randomized, Placebo-Controlled Trial of Bumetanide in Parkinson's Disease.

BACKGROUND: Acting on the main target of dopaminergic cells, the striatal γ-aminobutyric acid (GABA)-ergic cells, might be a new way to treat persons with Parkinson's disease (PD). OBJECTIVE: The objective of this study was to assess the efficacy of bumetanide, an Na-K-Cl cotransporter (NKCC1) inhibitor, to improve motor symptoms in PD. METHODS: This was a 4-month double-blind, randomized, parallel-group, placebo-controlled trial of 1.75 to 3 mg/day bumetanide as an adjunct to levodopa in 44 participants with PD and motor fluctuations. RESULTS: Compared to the baseline, the mean change in OFF Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III score after 4 months of treatment (primary endpoint) did not improve significantly compared with placebo. No changes between participants treated with bumetanide and those treated with placebo were observed for most other outcome measures. Despite no relevant safety signals, bumetanide was poorly tolerated. CONCLUSIONS: There was no evidence in this study that bumetanide has efficacy in improving motor symptoms of PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

TMEM151A as an alternative to PRRT2 in paroxysmal kinesigenic dyskinesia: About three new cases.

Paroxysmal kinesigenic dyskinesia (PKD) are movement disorders triggered by sudden voluntary movement. Variants in the TMEM151A gene have recently been associated with the development of PKD. We report three patients presenting PKD with different TMEM151A mutations, two of which have not been described yet.

Video-Based Automated Assessment of Movement Parameters Consistent with MDS-UPDRS III in Parkinson's Disease.

BACKGROUND: Among motor symptoms of Parkinson's disease (PD), including rigidity and resting tremor, bradykinesia is a mandatory feature to define the parkinsonian syndrome. MDS-UPDRS III is the worldwide reference scale to evaluate the parkinsonian motor impairment, especially bradykinesia. However, MDS-UPDRS III is an agent-based score making reproducible measurements and follow-up challenging. OBJECTIVE: Using a deep learning approach, we developed a tool to compute an objective score of bradykinesia based on the guidelines of the gold-standard MDS-UPDRS III. METHODS: We adapted and applied two deep learning algorithms to detect a two-dimensional (2D) skeleton of the hand composed of 21 predefined points, and transposed it into a three-dimensional (3D) skeleton for a large database of videos of parkinsonian patients performing MDS-UPDRS III protocols acquired in the Movement Disorder unit of Avicenne University Hospital. RESULTS: We developed a 2D and 3D automated analysis tool to study the evolution of several key parameters during the protocol repetitions of the MDS-UPDRS III. Scores from 2D automated analysis showed a significant correlation with gold-standard ratings of MDS-UPDRS III, measured with coefficients of determination for the tapping (0.609) and hand movements (0.701) protocols using decision tree algorithms. The individual correlations of the different parameters measured with MDS-UPDRS III scores carry meaningful information and are consistent with MDS-UPDRS III guidelines. CONCLUSION: We developed a deep learning-based tool to precisely analyze movement parameters allowing to reliably score bradykinesia for parkinsonian patients in a MDS-UPDRS manner.

Comparison of Botulinum neurotoxin efficiency in dystonia associated with Parkinson's disease and atypical parkinsonism: a retrospective study with a self-reported improvement scale.

Botulinum neurotoxin (BoNT) is a useful therapeutic option to treat dystonic manifestations. Data on its efficiency on dystonia associated with Parkinson's disease (PD) or atypical parkinsonism (AP) are scarce and no comparison of the efficiency of BoNT has been performed between these diseases and between the different localizations of dystonia in these pathologies. We retrospectively collected from patients' medical records the result of 611 BoNT injections in 63 dystonic parkinsonian patients (44 PD and 19 AP) using a self-reported clinical improvement scale and duration of effect. Using these data, we modeled the degree of improvement and its duration after BoNT treatment with a linear mixed model. This allowed us to assess the influence of clinical parameters on the reported treatment efficiency. On a scale from 0 to 100, patients with PD and AP, respectively, report a mean improvement of 69% and 55% after BoNT injection and it is similar regarding the different localizations of dystonia. Duration of effect is, however, longer in PD compared to AP (P = 0.023). Patients' demographic and clinical characteristics had no effect on the degree of improvement or duration of effect. Overall, our results support the use of BoNT in the various dystonic phenomena associated with degenerative parkinsonian syndromes. Shorter delays between injection sessions should be considered in AP compared to PD.Trial registration: This study was registered on Clinicaltrial.gov (NCT04948684).

Clinical and Radiological Follow-Up of a Pfizer-BioNTech COVID-19 Vaccine-Induced Hemichorea-Hemiballismus.

Background: Hemichorea-hemiballismus is a rare hyperkinetic movement disorder. Case Report: A 90-year-old male developed left hemichorea-hemiballismus after his second dose of the Pfizer-BioNTech COVID-19 vaccine. A wide range of investigations including magnetic resonance imaging did not reveal an alternative cause. [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) showed increases in right putamen fixation compared to the left side. The patient showed significant improvement after five days of intravenous corticosteroids, with a normal FDG-PET. Discussion: This hemichorea-hemiballismus case shows dynamic restoration of putamen metabolism mirroring clinical evolution after administration of corticosteroids, suggesting an autoimmune COVID-19 vaccine-induced reaction.

Neurological consequences of recreational nitrous oxide abuse during SARS-CoV-2 pandemic.

INTRODUCTION: Recreational use of nitrous oxide (N2O) is a growing practice in France and all around the world and is often associated with neurological complications. We report detailed clinical and paraclinical presentations of 12 patients with combined degeneration of the spinal cord and peripheral neuropathies in relation to N2O consumption, possibly favored by lockdowns due to SARS-CoV-2 pandemic. RESULTS: With variable levels of consumption, the 12 patients presented spinal cord and/or peripheral nerve damage, with mostly motor and ataxic symptoms, motor axonal nerve damage, and medullary T2-weighted hyperintensities on MRI. There was a clear improvement in symptoms after vitamin B12 substitution, although some sequelae remained, particularly sensory. DISCUSSION: We report detailed clinical, electrophysiological, radiological, and biological consequences of N2O abuse in 12 patients. Our data support the clinical and paraclinical observations reported in the literature. The mechanisms of neurological N2O toxicity are still debated. There is currently no precise recommendation on the therapeutic management. The clinical evolution after vitamin B12 substitution seems sufficient but could depend on early management. Effective messages targeting at risk population, but also the health professionals involved, seem crucial as does a better legal framework for this growing practice.

A short course of corticosteroids reduces the risk of mechanical ventilation and death in patients with moderate to severe COVID 19 pneumonia: results of a retrospective monocentric cohort.

BACKGROUND: Reduced mortality at 28 days in patients treated with corticosteroids was demonstrated, but this result was not confirmed by certain large epidemiological studies. Our aim was to determine whether corticosteroids improve the outcomes of our patients hospitalized with COVID-19 pneumonia. METHODS: Our retrospective, single centre cohort study included consecutive patients hospitalized for moderate to severe COVID-19 pneumonia between March 15 and April 15 2020. An early short course of corticosteroids was given during the second phase of the study. The primary composite endpoint was the need for mechanical ventilation or mortality within 28 days of admission. A multivariate logistic regression model was used to estimate the propensity score, i.e. the probability of each patient receiving corticosteroid therapy based on the initial variables. RESULTS: About 120 consecutive patients were included, 39 in the "corticosteroids group", 81 in the "no corticosteroids group"; their mean ages (±SD) were 66.4 ± 14.1 and 66.1 ± 15.2 years, respectively. Mechanical ventilation-free survival at 28 days was higher in the "corticosteroids group" than in the "no corticosteroids group" (71% and 29% of cases, respectively, p < .0001). The effect of corticosteroids was confirmed with HR .28 (95%CI .10-.79), p = .02. In older and comorbid patients who were not eligible for intensive care, the effect of corticosteroid therapy was also beneficial (HR .36 (95%CI .16-.80), p = .01). CONCLUSION: A short course of corticosteroids reduced the risks of death or mechanical ventilation in patients with moderate to severe COVID-19 pneumonia in all patients and also in older and comorbid patients not eligible for intensive care.

[Movement disorders in the elderly]. / Mouvements anormaux chez le sujet âgé.

Movement disorders are frequent in the elderly, with various presentations and causes. We review the most frequent movement disorders encountered in the elderly. Their diagnosis, mainly based on clinical examination, is necessary due to their common occurrence and their impact on autonomy. Tremor is the most frequent movement disorder, including essential tremor and Parkinson's disease. Iatrogenic or metabolic causes should always be explored in case of any movement disorder. Many treatments can induce movement disorders, especially in the elderly, often heavily treated by medications in patients with impaired renal or/and hepatic function. Other causes of movement disorders that may be encountered in the elderly and their treatment are described. Treatment will be started according to the ratio between the benefit of the functional gain and iatrogenic risk in these frailed subjects.

Multimodal magnetic resonance imaging investigation of basal forebrain damage and cognitive deficits in Parkinson's disease.

BACKGROUND: Cognitive deficits in Parkinson's disease (PD) may result from damage in the cortex as well as in the dopaminergic, noradrenergic, and cholinergic inputs to the cortex. Cholinergic inputs to the cortex mainly originate from the basal forebrain and are clustered in several regions, called Ch1 to Ch4, that project to the hippocampus (Ch1-2), the olfactory bulb (Ch3), and the cortex and amygdala (Ch4). OBJECTIVE: We investigated changes in basal forebrain and their role in cognitive deficits in PD. METHODS: We studied 52 nondemented patients with PD (Hoehn & Yahr 1-2) and 25 age-matched healthy controls using diffusion and resting state functional MRI. RESULTS: PD patients had a loss of structural integrity within the Ch1-2 and Ch3-4 nuclei of the basal forebrain as well as in the fornix. Tractography showed that the probability of anatomical connection was decreased in PD between Ch3-4 and the associative prefrontal cortex, occipital cortex, and peri-insular regions. There was a reduction in functional connectivity between Ch1-2 and the bilateral hippocampi and parahippocampal gyri, the left middle and superior temporal gyri, and the left fusiform gyrus and between Ch3-4 and the right inferior frontal gyrus and the right and left thalamus. In Ch1-2, loss of structural integrity and connectivity correlated with scores at the memory tests, whereas changes in Ch3-4 correlated with scores of global cognition and executive functions. CONCLUSION: This study highlights the association between deficits of different cholinergic nuclei of the basal forebrain and the extent of cognitive impairments in nondemented PD patients. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Tremor Associated with Chronic Inflammatory Demyelinating Polyneuropathy and Anti-Neurofascin-155 Antibodies.

Background: Tremor is an underrecognized feature in certain neuropathy subtypes. Phenomenology shown: We show a patient with a disabling neuropathic tremor and mild cerebellar syndrome associated with chronic inflammatory demyelinating polyneuropathy (CIDP) and anti-neurofascin-155 (NF155) antibodies. Educational value: Anti-NF155 testing should be considered in patients with CIDP and disabling tremor because of therapeutic implications.

Medulla oblongata damage and cardiac autonomic dysfunction in Parkinson disease.

OBJECTIVE: To characterize medulla oblongata damage using diffusion tensor imaging (DTI) in Parkinson disease (PD) and correlate it with dysfunction of the cardiac sympathetic/vagal balance. METHODS: Fifty-two patients with PD and 24 healthy controls were included in the study. All participants underwent clinical examination and 3T MRI using 3D T1-weighted imaging and DTI. DTI metrics were calculated within manually drawn regions of interest. Heart rate variability was evaluated using spectral analysis of the R-R cardiac interval during REM and slow-wave sleep based on continuous overnight electrocardiographic monitoring. Respiratory frequency was measured in 30-second contiguous epochs of REM and slow-wave sleep. The relationships between imaging and cardiac variables were calculated using partial correlations followed by the multiple comparisons permutation approach. RESULTS: The changes in heart rate and respiratory frequency variability from slow-wave sleep to REM sleep in healthy controls were no longer detectable in patients with PD. There were significant increases in the mean (p = 0.006), axial (p = 0.006), and radial diffusivities (p = 0.005) in the medulla oblongata of patients with PD. In PD, diffusion changes were specifically correlated with a lower heart rate and respiratory frequency variability during REM sleep. CONCLUSIONS: This study provides evidence that medulla oblongata damage underlies cardiac sympathetic/vagal balance and respiratory dysfunction in patients with PD.

Progressive Ataxia and Palatal Tremor: Think about POLG Mutations.

BACKGROUND: Progressive ataxia and palatal tremor (PAPT) can be observed in both acquired brainstem or cerebellar lesions and genetic disorders. PHENOMENOLOGY SHOWN: PAPT due to mutation in POLG, the gene encoding the mitochondrial DNA polymerase. EDUCATIONAL VALUE: POLG mutation should be considered in patients with PAPT, particularly when additional clues such as a sensory neuronopathy or an ophthalmoplegia are present.

Paroxysmal Exercise-induced Dyskinesias Caused by GLUT1 Deficiency Syndrome.

BACKGROUND: Glucose transporter type 1 deficiency syndrome is due to de novo mutations in the SLC2A1 gene encoding the glucose transporter type 1. PHENOMENOLOGY SHOWN: Paroxysmal motor manifestations induced by exercise or fasting may be the main manifestations of glucose transporter type 1 deficiency syndrome. EDUCATIONAL VALUE: Proper identification of the paroxysmal events and early diagnosis is important since the disease is potentially treatable.