Association of abnormal explicit sense of agency with cerebellar impairment in myoclonus-dystonia.

Non-motor aspects in dystonia are now well recognized. The sense of agency, which refers to the experience of controlling one's own actions, has been scarcely studied in dystonia, even though its disturbances can contribute to movement disorders. Among various brain structures, the cerebral cortex, the cerebellum, and the basal ganglia are involved in shaping the sense of agency. In myoclonus dystonia, resulting from a dysfunction of the motor network, an altered sense of agency may contribute to the clinical phenotype of the condition. In this study, we compared the explicit and implicit sense of agency in patients with myoclonus dystonia caused by a pathogenic variant of SGCE (DYT-SGCE) and control participants. We utilized behavioural tasks to assess the sense of agency and performed neuroimaging analyses, including structural, resting-state functional connectivity, and dynamic causal modelling, to explore the relevant brain regions involved in the sense of agency. Additionally, we examined the relationship between behavioural performance, symptom severity, and neuroimaging findings. We compared 19 patients with DYT-SGCE and 24 healthy volunteers. Our findings revealed that patients with myoclonus-dystonia exhibited a specific impairment in explicit sense of agency, particularly when implicit motor learning was involved. However, their implicit sense of agency remained intact. These patients also displayed grey-matter abnormalities in the motor cerebellum, as well as increased functional connectivity between the cerebellum and pre-supplementary motor area. Dynamic causal modelling analysis further identified reduced inhibitory effects of the cerebellum on the pre-supplementary motor area, decreased excitatory effects of the pre-supplementary motor area on the cerebellum, and increased self-inhibition within the pre-supplementary motor area. Importantly, both cerebellar grey-matter alterations and functional connectivity abnormalities between the cerebellum and pre-supplementary motor area were found to correlate with explicit sense of agency impairment. Increased self-inhibition within the pre-supplementary motor area was associated with less severe myoclonus symptoms. These findings highlight the disruption of higher-level cognitive processes in patients with myoclonus-dystonia, further expanding the spectrum of neurological and psychiatric dysfunction already identified in this disorder.

Contribution of MRI for the Early Diagnosis of Parkinsonism in Patients with Diagnostic Uncertainty.

BACKGROUND: International clinical criteria are the reference for the diagnosis of degenerative parkinsonism in clinical research, but they may lack sensitivity and specificity in the early stages. OBJECTIVES: To determine whether magnetic resonance imaging (MRI) analysis, through visual reading or machine-learning approaches, improves diagnostic accuracy compared with clinical diagnosis at an early stage in patients referred for suspected degenerative parkinsonism. MATERIALS: Patients with initial diagnostic uncertainty between Parkinson's disease (PD), progressive supranuclear palsy (PSP), and multisystem atrophy (MSA), with brain MRI performed at the initial visit (V1) and available 2-year follow-up (V2), were included. We evaluated the accuracy of the diagnosis established based on: (1) the international clinical diagnostic criteria for PD, PSP, and MSA at V1 ("Clin1"); (2) MRI visual reading blinded to the clinical diagnosis ("MRI"); (3) both MRI visual reading and clinical criteria at V1 ("MRI and Clin1"), and (4) a machine-learning algorithm ("Algorithm"). The gold standard diagnosis was established by expert consensus after a 2-year follow-up. RESULTS: We recruited 113 patients (53 with PD, 31 with PSP, and 29 with MSA). Considering the whole population, compared with clinical criteria at the initial visit ("Clin1": balanced accuracy, 66.2%), MRI visual reading showed a diagnostic gain of 14.3% ("MRI": 80.5%; P = 0.01), increasing to 19.2% when combined with the clinical diagnosis at the initial visit ("MRI and Clin1": 85.4%; P < 0.0001). The algorithm achieved a diagnostic gain of 9.9% ("Algorithm": 76.1%; P = 0.08). CONCLUSION: Our study shows the use of MRI analysis, whether by visual reading or machine-learning methods, for early differentiation of parkinsonism. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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.

Could motor blocks be a therapeutic option for treatment-resistant functional dystonia? A case series of three patients.

The diagnosis of functional dystonia is challenging because it is difficult to distinguish functional dystonia from other types of dystonia. After diagnostic explanation, multidisciplinary care is recommended, but some patients are resistant to treatments. We used motor blocks in three patients with severe resistant functional dystonia of the upper limbs to test (i) whether joint contracture was present and (ii) whether motor blocks have a therapeutic effect on functional dystonia. Patient 1 showed a good and sustained therapeutic response, Patient 2 experienced a resolution of the dystonic posture that lasted for 10 days, and Patient 3 experienced no effect. Motor blocks may be a useful therapeutic option in chronic treatment-resistant functional dystonia. The treatment effect might be achieved through the experience of normal positioning and functioning of the limb.

Clinical and genetic keys to cerebellar ataxia due to FGF14 GAA expansions.

BACKGROUND: SCA27B caused by FGF14 intronic heterozygous GAA expansions with at least 250 repeats accounts for 10-60% of cases with unresolved cerebellar ataxia. We aimed to assess the size and frequency of FGF14 expanded alleles in individuals with cerebellar ataxia as compared with controls and to characterize genetic and clinical variability. METHODS: We sized this repeat in 1876 individuals from France sampled for research purposes in this cross-sectional study: 845 index cases with cerebellar ataxia and 324 affected relatives, 475 controls, as well as 119 cases with spastic paraplegia, and 113 with familial essential tremor. FINDINGS: A higher frequency of expanded allele carriers in index cases with ataxia was significant only above 300 GAA repeats (10.1%, n = 85) compared with controls (1.1%, n = 5) (p < 0.0001) whereas GAA250-299 alleles were detected in 1.7% of both groups. Eight of 14 index cases with GAA250-299 repeats had other causal pathogenic variants (4/14) and/or discordance of co-segregation (5/14), arguing against GAA causality. We compared the clinical signs in 127 GAA≥300 carriers to cases with non-expanded GAA ataxia resulting in defining a key phenotype triad: onset after 45 years, downbeat nystagmus, episodic ataxic features including diplopia; and a frequent absence of dysarthria. All maternally transmitted alleles above 100 GAA were unstable with a median expansion of +18 repeats per generation (r2 = 0.44; p < 0.0001). In comparison, paternally transmitted alleles above 100 GAA mostly decreased in size (-15 GAA (r2 = 0.63; p < 0.0001)), resulting in the transmission bias observed in SCA27B pedigrees. INTERPRETATION: SCA27B diagnosis must consider both the phenotype and GAA expansion size. In carriers of GAA250-299 repeats, the absence of documented familial transmission and a presentation deviating from the key SCA27B phenotype, should prompt the search for an alternative cause. Affected fathers have a reduced risk of having affected children, which has potential implications for genetic counseling. FUNDING: This work was supported by the Fondation pour la Recherche Médicale, grant number 13338 to JLM, the Association Connaître les Syndrome Cérébelleux - France (to GS) and by the European Union's Horizon 2020 research and innovation program under grant agreement No 779257 ("SOLVE-RD" to GS). DP holds a Fellowship award from the Canadian Institutes of Health Research (CIHR). SK received a grant (01GM1905C) from the Federal Ministry of Education and Research, Germany, through the TreatHSP network. This work was supported by the Australian Government National Health and Medical Research Council grants (GNT2001513 and MRFF2007677) to MB and PJL.

Trial of Botulinum Toxin for Isolated or Essential Head Tremor.

BACKGROUND: Local injections of botulinum toxin type A have been used to treat essential head tremor but have not been extensively studied in randomized trials. METHODS: In a multicenter, double-blind, randomized trial, we assigned, in a 1:1 ratio, adult patients with essential or isolated head tremor to receive botulinum toxin type A or placebo. Botulinum toxin or placebo was injected under electromyographic guidance into each splenius capitis muscle on the day of randomization (day 0) and during week 12. The primary outcome was improvement by at least 2 points on the Clinical Global Impression of Change (CGI) scale at week 6 after the second injection (week 18 after randomization). The CGI scale was used to record the patient's assessment of the degree of improvement or worsening of head tremor since baseline; scores range from 3 (very much improved) to -3 (very much worse). Secondary outcomes included changes in tremor characteristics from baseline to weeks 6, 12, and 24. RESULTS: A total of 120 patients were enrolled; 3 patients were excluded during screening, and 117 patients were randomly assigned to receive botulinum toxin (62 patients) or placebo (55 patients) and were included in the intention-to-treat analysis. Twelve patients in the botulinum toxin group and 2 patients in the placebo group did not receive injections during week 12. The primary outcome - improvement by at least 2 points on the CGI scale at week 18 - was met by 31% of the patients in the botulinum toxin group as compared with 9% of those in the placebo group (relative risk, 3.37; 95% confidence interval, 1.35 to 8.42; P = 0.009). Analyses of secondary outcomes at 6 and 12 weeks but not at 24 weeks were generally supportive of the primary-outcome analysis. Adverse events occurred in approximately half the patients in the botulinum toxin group and included head and neck pain, posterior cervical weakness, and dysphagia. CONCLUSIONS: Injection of botulinum toxin into each splenius capitis muscle on day 0 and during week 12 was more effective than placebo in reducing the severity of isolated or essential head tremor at 18 weeks but not at 24 weeks, when the effects of injection might be expected to wane, and was associated with adverse events. (Funded by the French Ministry of Health; Btx-HT ClinicalTrials.gov number, NCT02555982.).

Is the clinical phenotype impact the prognosis in dementia with Lewy bodies?

INTRODUCTION: The first predominant clinical symptoms of dementia with Lewy bodies (DLB) are highly variable; however, the prognosis based on initial predominant symptoms remains poorly understood. METHODS: Multicenter retrospective study in 4 French expert neurological centers. Patients were categorized in 3 groups according to their first more predominant symptoms: cognitive, psychiatric, or motor. RESULTS: Analysis of 310 DLB patients. The mean age was 73.5 years old (SD 7.5) including 32.3% of women. The mean follow-up was 7.25 years (SD 3.6). We observed that the full clinical picture was more frequent in the motor group than in the cognitive group (p = 0.01); male gender and age at onset were associated with a significant excess risk of instantaneous mortality (p = 0.01). CONCLUSION: Initial symptoms may affect the clinical course of patients, but no significant difference in mortality was observed.

[Diagnostic criteria, epidemiology and assessment of patients with functional neurological disorders]. / Définitions, épidémiologie et démarche diagnostique clinique dans les troubles neurologiques fonctionnels.

Functional neurological disorders (FND) are symptoms that can affect a variety of functions including motor, sensory and cognitive. These symptoms are genuinely experienced by the patient and are related to a functional disorder rather than a structural one. There is little epidemiological data on these disorders, but their frequency is well established in clinical practice, it is the second most frequent reason for consultation in Neurology. Despite of the frequency of the disorder, general practitioners and specialists are insufficiently trained in the disease, and patients often suffer from stigmatization and/or unnecessary investigations. It is therefore important to be aware of the diagnostic approach to FND, which mostly relies on positive clinical signs. Psychiatric evaluation can help with the characterization of predisposing, precipitating and perpetuating factors of the symptoms (according to the 3P biopsychosocial model related to FND), and guide their management. Finally, diagnosis explanation is a crucial step in the management of the disease, which can in itself have a therapeutic effect, and allow the patient to adhere to the treatments.

[Functional neurological disorders: A clinical anthology]. / Troubles neurologiques fonctionnels : une anthologie clinique.

Functional neurological disorders have a broad phenotypic spectrum and include different clinical syndromes, which are sometimes associated to each other or appear consecutively over the course of the disease. This clinical anthology provides details on the specific and sensitive positive signs that are to be sought in the context of a suspected functional neurological disorder. Beside these positive elements leading to the diagnosis of functional neurological disorder, we should keep in mind the possibility of an associated organic disorder as the combination of both organic and functional disorders is a relatively frequent situation in clinical practice. Here we describe the clinical characteristics of different functional neurological syndromes: motor deficits, abnormal hyperkinetic and hypokinetic movements, voice or speech disorders, sensory disorders, and functional dissociative seizures. The clinical examination and the identification of positive signs play a critical role in the diagnosis of functional neurological disorder. Knowledge of the specific signs associated with each phenotype render possible to make an early diagnosis. For that matter, it contributes to the improvement of patient care management. It allows to a better engagement in an appropriate care pathway, which influence their prognosis. Highlighting and discussing positive signs with patients can also be an interesting step in the process of explaining the disease and its management.

Fixel-Based Analysis Reveals Whole-Brain White Matter Abnormalities in Cervical Dystonia.

BACKGROUND: Cervical dystonia (CD) is a form of isolated focal dystonia typically associated to abnormal head, neck, and shoulder movements and postures. The complexity of the clinical presentation limits the investigation of its pathophysiological mechanisms, and the neural networks associated to specific motor manifestations are still the object of debate. OBJECTIVES: We investigated the morphometric properties of white matter fibers in CD and explored the networks associated with motor symptoms, while regressing out nonmotor scores. METHODS: Nineteen patients affected by CD and 21 healthy controls underwent diffusion-weighted magnetic resonance imaging. We performed fixel-based analysis, a novel method evaluating fiber orientation within specific fiber bundles, and compared fiber morphometric properties between groups. Moreover, we correlated fiber morphometry with the severity of motor symptoms in patients. RESULTS: Compared to controls, patients exhibited decreased white matter fibers in the right striatum. Motor symptom severity negatively correlated with white matter fibers passing through inferior parietal areas and the head representation area of the motor cortex. CONCLUSIONS: Abnormal white matter integrity at the basal ganglia level may affect several functional networks involved, for instance, in motor preparation and execution, visuomotor coordination, and multimodal integration. This may result in progressive maladaptive plasticity, culminating in overt symptoms of dystonia. © 2023 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.

Neuromelanin-Sensitive Magnetic Resonance Imaging Changes in the Locus Coeruleus/Subcoeruleus Complex in Patients with Typical and Atypical Parkinsonism.

BACKGROUND: The locus coeruleus/subcoeruleus complex (LC/LsC) is a structure comprising melanized noradrenergic neurons. OBJECTIVE: To study the LC/LsC damage across Parkinson's disease (PD) and atypical parkinsonism in a large group of subjects. METHODS: We studied 98 healthy control subjects, 47 patients with isolated rapid eye movement sleep behavior disorder (RBD), 75 patients with PD plus RBD, 142 patients with PD without RBD, 19 patients with progressive supranuclear palsy (PSP), and 19 patients with multiple system atrophy (MSA). Twelve patients with MSA had proven RBD. LC/LsC signal intensity was derived from neuromelanin magnetic resonance imaging using automated software. RESULTS: The signal intensity was reduced in all parkinsonian syndromes compared with healthy control subjects, except in PD without RBD. The signal intensity decreased as age increased. Moreover, the signal intensity was lower in MSA than in isolated RBD and PD without RBD groups. In PD, the signal intensity correlated negatively with the percentage of REM sleep without atonia. There were no differences in signal intensity between PD plus RBD, PSP, and MSA. CONCLUSIONS: Neuromelanin signal intensity was reduced in all parkinsonian disorders, except in PD without RBD. The presence of RBD in parkinsonian disorders appears to be associated with lower neuromelanin signal intensity. Furthermore, lower LC/LsC signal changes in PSP could be partly caused by the effect of age. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Comparison of mean diffusivity, R2* relaxation rate and morphometric biomarkers for the clinical differentiation of parkinsonism.

INTRODUCTION: Quantitative biomarkers for clinical differentiation of parkinsonian syndromes are still lacking. Our aim was to evaluate the value of combining clinically feasible manual measurements of R2* relaxation rates and mean diffusivity (MD) in subcortical regions and brainstem morphometric measurements to improve the discrimination of parkinsonian syndromes. METHODS: Twenty-two healthy controls (HC), 25 patients with Parkinson's disease (PD), 19 with progressive supranuclear palsy (PSP) and 27 with multiple system atrophy (MSA, 21 with the parkinsonian variant -MSAp, 6 with the cerebellar variant -MSAc) were recruited. R2*, MD measurements and morphometric biomarkers including the midbrain to pons area ratio and the Magnetic Resonance Parkinsonism Index (MRPI) were compared between groups and their diagnostic performances were assessed. RESULTS: Morphometric biomarkers discriminated better patients with PSP (ratio: AUC 0.89, MRPI: AUC 0.89) and MSAc (ratio: AUC 0.82, MRPI: AUC 0.75) from other groups. R2* and MD measurements in the posterior putamen performed better in separating patients with MSAp from PD (R2*: AUC 0.89; MD: AUC 0.89). For the three-class classification "MSA vs PD vs PSP", the combination of MD and R2* measurements in the posterior putamen with morphometric biomarkers (AUC: 0.841) outperformed each marker separately. At the individual-level, there were seven discordances between imaging-based prediction and clinical diagnosis involving MSA. Using the new Movement Disorder Society criteria for the diagnosis of MSA, three of these seven patients were clinically reclassified as predicted by quantitative imaging. CONCLUSION: Combining R2* and MD measurements in the posterior putamen with morphometric biomarkers improves the discrimination of parkinsonism.

Impaired social cognition and fine dexterity in patients with Cowden syndrome associated with germline PTEN variants.

PURPOSE: Cowden syndrome (CS) is an autosomal dominant disease related to germline PTEN variants and is characterised by multiple hamartomas, increased risk of cancers and frequent brain alteration. Since the behaviour of patients with CS sometimes appears to be inappropriate, we analysed their neuropsychological functioning. METHODS: This monocentric study was conducted between July 2018 and February 2020. A standardised neuropsychological assessment, including an evaluation of social cognition, executive functions, language and dexterity, as well as a cerebral MRI were systematically proposed to all patients with CS. Moreover, PTEN variants were identified. RESULTS: Fifteen patients from 13 families were included, with six non-sense (40%), three missense (20%), five frameshift (33.3%) and one splice site (6.6%) variant types. Twelve patients (80%) had altered social cognition: 10 patients had an abnormal modified Faux-Pas score and 5 had Ekman's facial emotions recognition impairment. Nearly all patients (93%) had impaired dexterity. Cerebral MRI showed various cerebellar anomalies in seven patients (46.7%). CONCLUSION: Altered social cognition and impaired fine dexterity are frequently associated with CS. Further studies are needed to confirm these results and to determine whether dexterity impairment is due to the effect of germline PTEN variants in the cerebellum.

Older patients with COVID-19 and neuropsychiatric conditions: A study of risk factors for mortality.

BACKGROUND: Little is known about risk factors for mortality in older patients with COVID-19 and neuropsychiatric conditions. METHODS: We conducted a multicentric retrospective observational study at Assistance Publique-Hôpitaux de Paris. We selected inpatients aged 70 years or older, with COVID-19 and preexisting neuropsychiatric comorbidities and/or new neuropsychiatric manifestations. We examined demographics, comorbidities, functional status, and presentation including neuropsychiatric symptoms and disorders, as well as paraclinical data. Cox survival analysis was conducted to determine risk factors for mortality at 40 days after the first symptoms of COVID-19. RESULTS: Out of 191 patients included (median age 80 [interquartile range 74-87]), 135 (71%) had neuropsychiatric comorbidities including cognitive impairment (39%), cerebrovascular disease (22%), Parkinsonism (6%), and brain tumors (6%). A total of 152 (79%) patients presented new-onset neuropsychiatric manifestations including sensory symptoms (6%), motor deficit (11%), behavioral (18%) and cognitive (23%) disturbances, gait impairment (11%), and impaired consciousness (18%). The mortality rate at 40 days was 19.4%. A history of brain tumor or Parkinsonism or the occurrence of impaired consciousness were neurological factors associated with a higher risk of mortality. A lower Activities of Daily Living score (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.58-0.82), a neutrophil-to-lymphocyte ratio ≥ 9.9 (HR 5.69, 95% CI 2.69-12.0), and thrombocytopenia (HR 5.70, 95% CI 2.75-11.8) independently increased the risk of mortality (all p < .001). CONCLUSION: Understanding mortality risk factors in older inpatients with COVID-19 and neuropsychiatric conditions may be helpful to neurologists and geriatricians who manage these patients in clinical practice.

Relationship between Substantia Nigra Neuromelanin Imaging and Dual Alpha-Synuclein Labeling of Labial Minor in Salivary Glands in Isolated Rapid Eye Movement Sleep Behavior Disorder and Parkinson's Disease.

We investigated the presence of misfolded alpha-Synuclein (α-Syn) in minor salivary gland biopsies in relation to substantia nigra pars compacta (SNc) damage measured using magnetic resonance imaging in patients with isolated rapid eye movement sleep behavior disorder (iRBD) and Parkinson's disease (PD) as compared to healthy controls. Sixty-one participants (27 PD, 16 iRBD, and 18 controls) underwent a minor salivary gland biopsy and were scanned using a 3 Tesla MRI. Deposits of α-Syn were found in 15 (55.6%) PD, 7 (43.8%) iRBD, and 7 (38.9%) controls using the anti-aggregated α-Syn clone 5G4 antibody and in 4 (14.8%) PD, 3 (18.8%) iRBD and no control using the purified mouse anti-α-Syn clone 42 antibody. The SNc damages obtained using neuromelanin-sensitive imaging did not differ between the participants with versus without α-Syn deposits (irrespective of the antibodies and the disease group). Our study indicated that the α-Syn detection in minor salivary gland biopsies lacks sensitivity and specificity and does not correlate with the SNc damage, suggesting that it cannot be used as a predictive or effective biomarker for PD.

From anticipation to impulsivity in Parkinson's disease.

Anticipatory actions require to keep track of elapsed time and inhibitory control. These cognitive functions could be impacted in Parkinson's disease (iPD). To test this hypothesis, a saccadic reaction time task was used where a visual warning stimulus (WS) predicted the occurrence of an imperative one (IS) appearing after a short delay. In the implicit condition, subjects were not informed about the duration of the delay, disfavoring anticipatory behavior but leaving inhibitory control unaltered. In the explicit condition, delay duration was cued. This should favor anticipatory behavior and perhaps alter inhibitory control. This hypothesis was tested in controls (N = 18) and age-matched iPD patients (N = 20; ON and OFF L-DOPA). We found that the latency distribution of saccades before the IS was bimodal. The 1st mode weakly depended on temporal information and was more prominent in iPD. Saccades in this mode were premature and could result of a lack of inhibition. The 2nd mode covaried with cued duration suggesting that these movements were genuine anticipatory saccades. The explicit condition increased the probability of anticipatory saccades before the IS in controls and iPDON but not iPDOFF patients. Furthermore, in iPD patients the probability of sequences of 1st mode premature responses increased. In conclusion, the triggering of a premature saccade or the initiation of a controlled anticipatory one could be conceptualized as the output of two independent stochastic processes. Altered time perception and increased motor impulsivity could alter the balance between these two processes in favor of the latter in iPD, particularly OFF L-Dopa.

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).