Movement Deficits Research Articles

TRPV4 contributes to ER stress and inflammation: implications for Parkinson\u2019s disease

BackgroundParkinson’s disease (PD) is a progressive neurodegenerative disorder. Its molecular mechanism is still unclear, and pharmacological treatments are unsatisfactory. Transient receptor potential vanilloid 4 (TRPV4) is a nonselective Ca2+ channel. It has recently emerged as a critical risk factor in the pathophysiology of neuronal injuries and cerebral diseases. Our previous study reported that TRPV4 contributed to endoplasmic reticulum (ER) stress in the MPP+-induced cell model of PD. In the present study, we detected the role and the mechanism of TRPV4 in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice.MethodsIntracerebral injection of an adeno-associated virus (AAV) into the substantia nigra (SN) of mice was used to knockdown or upregulate the expression of TRPV4 and intraperitoneal injection of MPTP. Rotarod and pole tests were used to evaluate the locomotor ability of mice. We used immunohistochemistry, Nissl staining and Western blot to detect the alterations in the number of tyrosine hydroxylase (TH)-positive neurons, Nissl-positive neurons, the levels of ER stress-associated molecules and proinflammatory cytokines in the SN.ResultsThe SN was transfected with AAV for 3 weeks and expressed the target protein with green fluorescence. Knockdown of TRPV4 via injection of a constructed AAV-TRPV4 shRNAi into the SN alleviated the movement deficits of PD mice. Upregulation of TRPV4 via injection of a constructed AAV-TRPV4 aggravated the above movement disorders. The expression of TRPV4 was upregulated in the SN of MPTP-treated mice. Injection of AAV-TRPV4 shRNAi into the SN rescued the number of TH-positive and Nissl-positive neurons in the SN decreased by MPTP, while injection of AAV-TRPV4 induced the opposite effect. Moreover, MPTP-decreased Sarco/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2) and pro-cysteinyl aspartate specific proteinase-12 (procaspase-12), MPTP-increased Glucose-regulated protein 78 (GRP78), Glucose-regulated protein 94 (GRP94) and C/EBP homologous protein (CHOP) were inhibited by AAV-TRPV4 shRNAi infection, and enhanced by AAV-TRPV4. In the same way, MPTP-decreased procaspase-1, MPTP-increased Interleukin-18 (IL-18), Cyclooxgenase-2 (COX-2) and 5-Lipoxygenase (5-LOX) were inhibited by AAV-TRPV4 shRNAi, or further exacerbated by AAV-TRPV4.ConclusionsThese results suggest that TRPV4 mediates ER stress and inflammation pathways, contributing to the loss of dopamine (DA) neurons in the SN and movement deficits in PD mice. Moreover, this study provides a new perspective on molecular targets and gene therapies for the treatment of PD in the future.

Assessing visually guided reaching in people with multiple sclerosis with and without self-reported upper limb impairment.

The ability to accurately complete goal-directed actions, such as reaching for a glass of water, requires coordination between sensory, cognitive and motor systems. When these systems are impaired, like in people with multiple sclerosis (PwMS), deficits in movement arise. To date, the characterization of upper limb performance in PwMS has typically been limited to results attained from self-reported questionnaires or clinical tools. Our aim was to characterize visually guided reaching performance in PwMS. Thirty-six participants (12 PwMS who reported upper limb impairment (MS-R), 12 PwMS who reported not experiencing upper limb impairment (MS-NR), and 12 age- and sex-matched control participants without MS (CTL)) reached to 8 targets in a virtual environment while seeing a visual representation of their hand in the form of a cursor on the screen. Reaches were completed with both the dominant and non-dominant hands. All participants were able to complete the visually guided reaching task, such that their hand landed on the target. However, PwMS showed noticeably more atypical reaching profiles when compared to control participants. In accordance with these observations, analyses of reaching performance revealed that the MS-R group was more variable with respect to the time it took to initiate and complete their movements compared to the CTL group. While performance of the MS-NR group did not differ significantly from either the CTL or MS-R groups, individuals in the MS-NR group were less consistent in their performance compared to the CTL group. Together these findings suggest that PwMS with and without self-reported upper limb impairment have deficits in the planning and/or control of their movements. We further argue that deficits observed during movement in PwMS who report upper limb impairment may arise due to participants compensating for impaired movement planning processes.

Linking Pain and Motor Control: Conceptualization of Movement Deficits in Patients With Painful Conditions.

This Perspective proposes that approaching PRMD from a contemporary motor control perspective will uncover key mechanisms, identify treatment targets, inform assessments, and innovate treatments across sensory-perceptual, cognitive, and motor domains, all of which have the potential to improve movement and functional outcomes in patients with painful conditions.

Student motivation to physical activity in the process of programming training

The article presents the experience of organizing the use of wearable electronic devices (fitness trackers) by schoolchildren to solve the problem of low physical activity. The existing methods of motivating schoolchildren to increase the level of physical activity do not give the desired result. Physical education classes in school cannot compensate for the movement deficit. During extracurricular hours, most schoolchildren also cannot organize their physical activity independently and choose sedentary types of leisure. One way to tackle the problem is to encourage the use of fitness trackers. The use of fitness trackers allows the teacher to monitor the level of physical activity of schoolchildren, analyze the achievements jointly, and help organize the physical activity of schoolchildren outside the classroom. To solve the problem, the authors of the article have developed two experimental programs of supplementary education for schoolchildren with the use of fitness trackers. The first program involves the regular, supervised use of fitness trackers in animation training. The second program includes training assignments for assembling and testing fitness trackers in the course of programming training. The second program showed higher efficiency. For the statistical assessment of the results of the educational programs implementation, the Wilcoxon T-test was used. The implementation of educational programs led to increase of the level of physical activity of students by 7–15 %. The authors give recommendations on the use of fitness trackers in the supplementary education system.

Identification of Novel Therapeutic Targets for Polyglutamine Diseases That Target Mitochondrial Fragmentation.

Huntington’s disease (HD) is one of at least nine polyglutamine diseases caused by a trinucleotide CAG repeat expansion, all of which lead to age-onset neurodegeneration. Mitochondrial dynamics and function are disrupted in HD and other polyglutamine diseases. While multiple studies have found beneficial effects from decreasing mitochondrial fragmentation in HD models by disrupting the mitochondrial fission protein DRP1, disrupting DRP1 can also have detrimental consequences in wild-type animals and HD models. In this work, we examine the effect of decreasing mitochondrial fragmentation in a neuronal C. elegans model of polyglutamine toxicity called Neur-67Q. We find that Neur-67Q worms exhibit mitochondrial fragmentation in GABAergic neurons and decreased mitochondrial function. Disruption of drp-1 eliminates differences in mitochondrial morphology and rescues deficits in both movement and longevity in Neur-67Q worms. In testing twenty-four RNA interference (RNAi) clones that decrease mitochondrial fragmentation, we identified eleven clones—each targeting a different gene—that increase movement and extend lifespan in Neur-67Q worms. Overall, we show that decreasing mitochondrial fragmentation may be an effective approach to treating polyglutamine diseases and we identify multiple novel genetic targets that circumvent the potential negative side effects of disrupting the primary mitochondrial fission gene drp-1.

Looking "Cherry Red Spot Myoclonus" in the Eyes: Clinical Phenotype, Treatment Response, and Eye Movements in Sialidosis Type 1.

Sialidosis type 1 is a rare lysosomal storage disorder caused by mutations of the neuraminidase gene. Specific features suggesting this condition include myoclonus, ataxia and macular cherry-red spots. However, phenotypic variability exists. Here, we present detailed clinical and video description of three patients with this rare condition. We also provide an in-depth characterization of eye movement abnormalities, as an additional tool to investigate pathophysiological mechanisms and to facilitate diagnosis. In our patients, despite phenotypic differences, eye movement deficits largely localized to the cerebellum.

GCH1 Deficiency Activates Brain Innate Immune Response and Impairs Tyrosine Hydroxylase Homeostasis.

The Parkinson's disease (PD) risk gene GTP cyclohydrolase 1 (GCH1) catalyzes the rate-limiting step in tetrahydrobiopterin (BH4) synthesis, an essential cofactor in the synthesis of monoaminergic neurotransmitters. To investigate the mechanisms by which GCH1 deficiency may contribute to PD, we generated a loss of function zebrafish gch1 mutant (gch1-/-), using CRISPR/Cas technology. gch1-/- zebrafish develop marked monoaminergic neurotransmitter deficiencies by 5 d postfertilization (dpf), movement deficits by 8 dpf and lethality by 12 dpf. Tyrosine hydroxylase (Th) protein levels were markedly reduced without loss of ascending dopaminergic (DAergic) neurons. L-DOPA treatment of gch1-/- larvae improved survival without ameliorating the motor phenotype. RNAseq of gch1-/- larval brain tissue identified highly upregulated transcripts involved in innate immune response. Subsequent experiments provided morphologic and functional evidence of microglial activation in gch1-/- The results of our study suggest that GCH1 deficiency may unmask early, subclinical parkinsonism and only indirectly contribute to neuronal cell death via immune-mediated mechanisms. Our work highlights the importance of functional validation for genome-wide association studies (GWAS) risk factors and further emphasizes the important role of inflammation in the pathogenesis of PD.SIGNIFICANCE STATEMENT Genome-wide association studies have now identified at least 90 genetic risk factors for sporadic Parkinson's disease (PD). Zebrafish are an ideal tool to determine the mechanistic role of genome-wide association studies (GWAS) risk genes in a vertebrate animal model. The discovery of GTP cyclohydrolase 1 (GCH1) as a genetic risk factor for PD was counterintuitive, GCH1 is the rate-limiting enzyme in the synthesis of dopamine (DA), mutations had previously been described in the non-neurodegenerative movement disorder dopa-responsive dystonia (DRD). Rather than causing DAergic cell death (as previously hypothesized by others), we now demonstrate that GCH1 impairs tyrosine hydroxylase (Th) homeostasis and activates innate immune mechanisms in the brain and provide evidence of microglial activation and phagocytic activity.

Smooth Pursuit Eye Movements as a Biomarker for Mild Concussion within 7-Days of Injury

ABSTRACT Aim Deficits in smooth-pursuit eye movements (SPEM) are often associated with mild traumatic brain injury(TBI). Eye tracking tests serve as a quick objective clinical tool to assess such predictive visual tracking. In this study, SPEM was assessed along circular, horizontal and vertical trajectories in adolescents with concussion and age-matched controls. Methods Ninety-one young adolescents with concussion and 140 visually healthy age-matched controls with a mean age of 14 years performed a computerized test of circular, horizontal and vertical tracking task using an eye tracker. Oculomotor tracking was assessed by computing the rate of fixation, saccades and SPEM made while performing the tasks. Results The predictive visual tracking task was able to differentiate the TBI group from the non-TBI group. The TBI group showed a significant difference in the fixation, saccades and SPEM percentages for circular tracking movement compared to the controls. There was a significant difference in fixation and SPEM % for horizontal and vertical tracking. Conclusions Predictive visual tracking, assessed using eye tracking technology, is able to differentiate deficits in oculomotor functions in individuals with and without concussion. The eye tracking technology may serve as a quick objective tool to detect and monitor neural deficits due to TBI.

Quantity versus quality: Age-related differences in muscle volume, intramuscular fat, and mechanical properties in the triceps surae.

With aging comes reductions in the quality and size of skeletal muscle. These changes influence the force-generating capacity of skeletal muscle and contribute to movement deficits that accompany aging. Although declines in strength remain a significant barrier to mobility in older adults, the association between age-related changes in muscle structure and function remain unresolved. In this study, we compared age-related differences in (i) muscle volume and architecture, (ii) the quantity and distribution of intramuscular fat, and (iii) muscle shear modulus (an index of stiffness) in the triceps surae in 21 younger (24.6±4.3years) and 15 older (70.4±2.4years) healthy adults. Additionally, we explored the relationship between muscle volume, architecture, intramuscular fat and ankle plantar flexion strength in young and older adults. Magnetic resonance imaging was used to determine muscle volume and intramuscular fat content. B-mode ultrasound was used to quantify muscle architecture, shear-wave elastography was used to measure shear modulus, and ankle strength was measured during maximal isometric plantar flexion contractions. We found that older adults displayed higher levels of intramuscular fat yet similar muscle volumes in the medial (MG) and lateral gastrocnemius (LG) and soleus, compared to younger adults. These age-related higher levels of intramuscular fat were associated with lower muscle shear modulus in the LG and MG. We also found that muscle physiological cross-sectional area (PCSA) that accounted for age-associated differences in intramuscular fat showed a modest increase in its association with ankle strength compared to PCSA that did not account for fat content. This highlights that skeletal muscle fat infiltration plays a role in age-related strength deficits, but does not fully explain the age-related loss in muscle strength, suggesting that other factors play a more significant role.

Preservation of Eye Movements in Parkinson's Disease Is Stimulus- and Task-Specific.

Parkinson's disease (PD) is a neurodegenerative disease that includes motor impairments, such as tremor, bradykinesia, and postural instability. Although eye movement deficits are commonly found in saccade and pursuit tasks, preservation of oculomotor function has also been reported. Here we investigate specific task and stimulus conditions under which oculomotor function in PD is preserved. Sixteen PD patients and 18 healthy, age-matched controls completed a battery of movement tasks that included stationary or moving targets eliciting reactive or deliberate eye movements: pro-saccades, anti-saccades, visually guided pursuit, and rapid go/no-go manual interception. Compared with controls, patients demonstrated systematic impairments in tasks with stationary targets: pro-saccades were hypometric and anti-saccades were incorrectly initiated toward the cued target in ∼35% of trials compared with 14% errors in controls. In patients, task errors were linked to short latency saccades, indicating abnormalities in inhibitory control. However, patients' eye movements in response to dynamic targets were relatively preserved. PD patients were able to track and predict a disappearing moving target and make quick go/no-go decisions as accurately as controls. Patients' interceptive hand movements were slower on average but initiated earlier, indicating adaptive processes to compensate for motor slowing. We conclude that PD patients demonstrate stimulus and task dependency of oculomotor impairments, and we propose that preservation of eye and hand movement function in PD is linked to a separate functional pathway through the superior colliculus-brainstem loop that bypasses the fronto-basal ganglia network. Our results demonstrate that studying oculomotor and hand movement function in PD can support disease diagnosis and further our understanding of disease progression and dynamics.SIGNIFICANCE STATEMENT Eye movements are a promising clinical tool to aid in the diagnosis of movement disorders and to monitor disease progression. Although Parkinson's disease (PD) patients show some oculomotor abnormalities, it is not clear whether previously described eye movement impairments are task-specific. We assessed eye movements in PD under different visual (stationary vs moving targets) and movement (reactive vs deliberate) conditions. We demonstrate that PD patients are able to accurately track moving objects but make inaccurate eye movements toward stationary targets. The preservation of eye movements toward dynamic stimuli might enable patients to accurately act on the predicted motion path of the moving target. These results can inform the development of tools for the rehabilitation or maintenance of functional performance.

Wrist-mounted accelerometers provide objective evidence of disease and recovery in patients with frozen shoulder

BackgroundCommercially available wrist-mounted exercise monitors may offer objective data on disease and recovery. This study is the first to evaluate the potential of such devices in the assessment of frozen shoulder and the effects of treatment.MethodsTwenty-one patients with isolated, unilateral frozen shoulder wore a wrist-mounted accelerometer (Fitbit Fire II, Fitbit Inc. 2007, California, USA) on each wrist for two separate seven-day periods, one week before and six months after treatment. The monitors produced an activity count for each 24-hour period, accounting for all movements of the upper limb. Three values were calculated for each time period: (1) the mean activity count for each limb, (2) the total activity count for both limbs, and (3) an activity count ratio calculated by dividing the activity of the frozen limb by the unaffected limb. Constant score, American Shoulder and Elbow Surgeons, visual analog scale–pain, and range of movement were recorded before and after treatment.ResultsMean activity counts were significantly lower in the frozen shoulder limb than those in the unaffected limb over the initial seven-day period (6066 vs. 7516; P = .04). The activity count ratio significantly improved after treatment (0.83 vs. 096; p 0.01), whereas the mean total activity count remained similar before and after treatment (14915 vs. 12371; P = .18), demonstrating that activity transferred from the unaffected limb back to the previously frozen limb. Range of movement (P < .01), Constant (P < .01), American Shoulder and Elbow Surgeons (P < .01), and visual analog scale–pain (P < .01) scores all significantly improved after treatment, but there was no correlation with the data from the activity monitor.DiscussionWrist-mounted accelerometers are sufficiently sensitive to detect a difference in limb activity in patients affected by frozen shoulder. The movement deficit between the affected and unaffected limbs improved by 14% after treatment. These data could be used in conjunction with subjective scores to offer a clearer insight into patient disease burden and recovery.

An Emerging Role for Epigenetics in Cerebral Palsy.

Cerebral palsy is a set of common, severe, motor disabilities categorized by a static, nondegenerative encephalopathy arising in the developing brain and associated with deficits in movement, posture, and activity. Spastic CP, which is the most common type, involves high muscle tone and is associated with altered muscle function including poor muscle growth and contracture, increased extracellular matrix deposition, microanatomic disruption, musculoskeletal deformities, weakness, and difficult movement control. These muscle-related manifestations of CP are major causes of progressive debilitation and frequently require intensive surgical and therapeutic intervention to control. Current clinical approaches involve sophisticated consideration of biomechanics, radiologic assessments, and movement analyses, but outcomes remain difficult to predict. There is a need for more precise and personalized approaches involving omics technologies, data science, and advanced analytics. An improved understanding of muscle involvement in spastic CP is needed. Unfortunately, the fundamental mechanisms and molecular pathways contributing to altered muscle function in spastic CP are only partially understood. In this review, we outline evidence supporting the emerging hypothesis that epigenetic phenomena play significant roles in musculoskeletal manifestations of CP.

TWMP-02. Supplementary motor area syndrome in glioma surgery - towards a classification system based on clinical and imaging data

Abstract OBJECTIVES Surgical resection of gliomas involving the supplementary motor area (SMA) frequently results in a symptom complex commonly described as „SMA syndrome“, which is characterized by transient contralateral akinesia and mutism. As factors potentially influencing the severity and duration of symptoms still remain elusive, we aim to further investigate potential predictors in a multicentric cohort of glioma patients. METHODS Fifty patients with gliomas located in the superior frontal gyrus from 3 centers were included in this retrospective study. Patients with injury of M1 and/or the corticospinal tract were excluded. Early postoperative motor outcome, the occurrence of mutism and duration of acute symptoms in days were assessed. The long-term outcome was assessed in follow-up examinations 3 months after surgery. Atlas-based lesion-symptom mapping was performed using postoperative MR imaging estimating surgical grey matter damage as well as white matter disconnection severity. Associations between functional outcome and imaging findings were analyzed using group tests and correlation analyses. RESULTS Median duration of symptoms in the cohort was 3 days (range: 1 – 42 days). Persistent deficits concerning fine motor movements and speech after initial recovery were found in 27 patients (54%). Disconnection of the central segment of the corpus callosum was associated with longer symptom duration (FDR corr. p &amp;lt; 0.05), while disconnection of the mid-posterior segment of the corpus callosum was associated with persistent deficits at follow-up (FDR corr. p &amp;lt; 0.05). CONCLUSIONS The present study shows a high variability regarding the recovery time of postoperative SMA syndrome and a high prevalence of persistent deficits in fine motor movements and speech after initial recovery of acute symptoms. The pivotal role of interhemispheric connectivity in the recovery process is reinforced. These findings will help neurosurgeons in patient consultation and provide a foundation for future studies aiming to establish prediction models of the SMA syndrome.

Saccade and Fixation Eye Movements During Walking in People With Mild Traumatic Brain Injury.

Background: Clinical and laboratory assessment of people with mild traumatic brain injury (mTBI) indicate impairments in eye movements. These tests are typically done in a static, seated position. Recently, the use of mobile eye-tracking systems has been proposed to quantify subtle deficits in eye movements and visual sampling during different tasks. However, the impact of mTBI on eye movements during functional tasks such as walking remains unknown. Objective: Evaluate differences in eye-tracking measures collected during gait between healthy controls (HC) and patients in the sub-acute stages of mTBI recovery and to determine if there are associations between eye-tracking measures and gait speed. Methods: Thirty-seven HC participants and 67individuals with mTBI were instructed to walk back and forth over 10-m, at a comfortable self-selected speed. A single 1-min trial was performed. Eye-tracking measures were recorded using a mobile eye-tracking system (head-mounted infra-red Tobbii Pro Glasses 2, 100 Hz, Tobii Technology Inc. VA, United States). Eye-tracking measures included saccadic (frequency, mean and peak velocity, duration and distance) and fixation measurements (frequency and duration). Gait was assessed using six inertial sensors (both feet, sternum, right wrist, lumbar vertebrae and the forehead) and gait velocity was selected as the primary outcome. General linear model was used to compare the groups and association between gait and eye-tracking outcomes were explored using partial correlations. Results: Individuals with mTBI showed significantly reduced saccade frequency (p = 0.016), duration (p = 0.028) and peak velocity (p = 0.032) compared to the HC group. No significant differences between groups were observed for the saccade distance, fixation measures and gait velocity (p > 0.05). A positive correlation was observed between saccade duration and gait velocity only for participants with mTBI (p = 0.025). Conclusion: Findings suggest impaired saccadic eye movement, but not fixations, during walking in individuals with mTBI. These findings have implications in real-world function including return to sport for athletes and return to duty for military service members. Future research should investigate whether or not saccade outcomes are influenced by the time after the trauma and rehabilitation.

Infranuclear Eye Movement Disorders.

Infranuclear motility disorders are such of the cranial nerves, the extraocular muscles or changes in the orbit but definitely peripheral to the nuclei of the cranial nerves. Characteristic are movement deficits, a compensatory head posture and the pattern of incomitancy. The secondary angle of deviation is usually larger than the primary. Combined pareses suggest a lesion in the cavernous sinus, orbital apex or a multilocular event. It is essential to rule out supranuclear disorders, especially if the motility deficit is atypical. For clarification, an individual risk assessment is recommended, paying particular attention to risk factors.

Manganese exposure causes movement deficit and changes in the protein profile of the external globus pallidus in Sprague Dawley rats

Manganese (Mn) is required for normal brain development and function. Excess Mn may trigger a parkinsonian movement disorder but the underlying mechanisms are incompletely understood. We explored changes in the brain proteomic profile and movement behavior of adult Sprague Dawley (SD) rats systemically treated with or without 1.0 mg/mL MnCl2 for 3 months. Mn treatment significantly increased the concentration of protein-bound Mn in the external globus pallidus (GP), as demonstrated by inductively coupled plasma mass spectrometry. Behavioral study showed that Mn treatment induced movement deficits, especially of skilled movement. Proteome analysis by two-dimensional fluorescence difference gel electrophoresis coupled with mass spectrometry revealed 13 differentially expressed proteins in the GP of Mn-treated versus Mn-untreated SD rats. The differentially expressed proteins were mostly involved in glycolysis, metabolic pathways, and response to hypoxia. Selected pathway class analysis of differentially expressed GP proteins, which included phosphoglycerate mutase 1 (PGAM1), primarily identified enrichment in glycolytic process and innate immune response. In conclusion, perturbation of brain energy production and innate immune response, in which PGAM1 has key roles, may contribute to the movement disorder associated with Mn neurotoxicity.

Mouse model of voluntary movement deficits induced by needlestick injuries to the primary motor cortex

BackgroundMotor handicap is prevalent in patients with traumatic brain injury, but currently. there is a challenging task to prevent the degeneration of motor neurons and to fully recover the. voluntary movement after injury. New methodFor the first time, we propose to apply needlestick injuries to the primary motor cortex to create mouse model of voluntary movement deficits. Rotarod test, cylinder test and forepaw grip strength test were used to assay motor coordination of both C57BL/6 J and the triple immunodeficient NCG mice. Immunofluorescence staining of PKC-gamma, UCHL1, GFAP, Iba1 and Fluoro-Jade C was performed to analyze the numbers of motor neurons, microglia, astrocytes and degenerating neurons. ResultsMice on either C57BL/6 J or immunodeficient background with the unilateral primary motor cortex injury exhibit motor neuron death, activation of glial cells and deficits in voluntary movement. ConclusionsThe main finding of this study was that the unilateral primary motor cortex injured by needlesticks leads to reactive gliosis, motor neuron death and voluntary movement deficits in mice. This needlestick injury model of primary motor cortex might be useful for future exploration of underlying mechanisms of motor neuron degeneration and of promising treatment modalities such as cell transplantation to improve locomotor deficiency following neurotrauma.

Dupuytren\u2019s interventions surgery versus collagenase (DISC) trial: study protocol for a pragmatic, two-arm parallel-group, non-inferiority randomised controlled trial

BackgroundDupuytren’s contracture is a fibro-proliferative disease of the hands affecting over 2 million UK adults, particularly the white, male population. Surgery is the traditional treatment; however, recent studies have indicated that an alternative to surgery—collagenase clostridium histolyticum (collagenase)—is better than a placebo in the treatment of Dupuytren’s contracture. There is however no robust randomised controlled trial that provides a definitive answer on the clinical effectiveness of collagenase compared with limited fasciectomy surgery. Dupuytren’s intervention surgery vs collagenase trial (DISC) trial was therefore designed to fill this evidence gap.Methods/designThe DISC trial is a multi-centre pragmatic two-arm parallel-group, randomised controlled trial. Participants will be assigned 1:1 to receive either collagenase injection or surgery (limited fasciectomy).We aim to recruit 710 adult participants with Dupuytren’s contracture. Potential participants will be identified in primary and secondary care, screened by a delegated clinician and if eligible and consenting, baseline data will be collected and randomisation completed.The primary outcome will be the self-reported patient evaluation measure assessed 1 year after treatment. Secondary outcome measures include the Unité Rhumatologique des Affections de la Main Scale, the Michigan Hand Questionnaire, EQ-5D-5L, resource use, further procedures, complications, recurrence, total active movement and extension deficit, and time to return to function. Given the limited evidence comparing recurrence rates following collagenase injection and limited fasciectomy, and the importance of a return to function as soon as possible for patients, the associated measures for each will be prioritised to allow treatment effectiveness in the context of these key elements to be assessed.An economic evaluation will assess the cost-effectiveness of treatments, and a qualitative sub-study will assess participants’ experiences and preferences of the treatments.DiscussionThe DISC trial is the first randomised controlled trial, to our knowledge, to investigate the clinical and cost-effectiveness of collagenase compared to limited fasciectomy surgery for patients with Dupuytren’s contracture.Trial registrationClinical.Trials.gov ISRCTN18254597. Registered on April 11, 2017.

Eye movement deficits in Parkinson’s patients are compensated during go/no-go manual interceptions

Eye movement deficits in Parkinson’s patients are compensated during go/no-go manual interceptions

Application of Technologies Robotic Rehabilitation in Children with Upper Limb Injury

Robotic and advanced technology rehabilitation is useful for people with difficulties and deficits in arm and hand movements, walking problems and balance disorders. Robotic technologies are being introduced in the rehabilitation field to support the activity of specialists, doctors and physiotherapists; the future and the challenge of rehabilitation lies precisely in the development of robotics. Robot assists the therapist in administering the most appropriate motor therapy with precision and repeatability modulates the difficulty of the exercise. It allows repetitive task-oriented activities with augmentative feedback capable of inducing brain plasticity. It acquires quantitative information on movement and evaluates the services performed he first, “Arm and Hand”, is used to help the opening and closing movements of the hand. After entering it by hand and forearm, gently guides the patient’s shoulder and elbow movements to reach and grasp objects. “Wrist”, on the other hand, interacts with the movements of the wrist and integrates functionally with the “Hand” module.