Inhaled Levodopa (CVT-301) for the Treatment of Parkinson Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials

ABSTRACTPurposeof Review: To investigate the efficacy and safety of CVT-301 for motor fluctuation in Parkinson’s disease (PD).Recent Findings:This study demonstrated that the CVT-301 group had a higher proportion of patients achieving an ON state than the placebo group (OR=2.68; 95% CI: 1.86-3.86; p<0.00001). Moreover, CVT-301 had also shown to improve motor function by UPDRS-III score (SMD=3.83; 95% CI: 2.44-5.23; p<0.00001) and promote an overall improvement of PD by PGIC self-rating (OR=2.95; 95% CI: 1.78-4.9; p<0.00001). The most common adverse events encountered were respiratory symptoms (OR=12.18; 95% CI: 5.01-29.62; p<0.00001) and nausea (OR=3.95; 95% CI: 1.01-15.41; p=0.05).Summary:CVT-301 had the potential to be an alternative or even a preferred treatment for motor fluctuation in PD patients.

Sigma-1 Receptor is a Pharmacological Target to Promote Neuroprotection in the SOD1G93A ALS Mice

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized by the death of motoneurons (MNs) with a poor prognosis. There is no available cure, thus, novel therapeutic targets are urgently needed. Sigma-1 receptor (Sig-1R) has been reported as a target to treat experimental models of degenerative diseases and, importantly, mutations in the Sig-1R gene cause several types of motoneuron disease (MND). In this study we compared the potential therapeutic effect of three Sig-1R ligands, the agonists PRE-084 and SA4503 and the antagonist BD1063, in the SOD1G93A mouse model of ALS. Pharmacological administration was from 8 to 16 weeks of age, and the neuromuscular function and disease progression were evaluated using nerve conduction and rotarod tests. At the end of follow up (16 weeks), samples were harvested for histological and molecular analyses. The results showed that PRE-084, as well as BD1063 treatment was able to preserve neuromuscular function of the hindlimbs and increased the number of surviving MNs in the treated female SOD1G93A mice. SA4503 tended to improve motor function and preserved neuromuscular junctions (NMJ), but did not improve MN survival. Western blot analyses revealed that the autophagic flux and the endoplasmic reticulum stress, two pathways implicated in the physiopathology of ALS, were not modified with Sig-1R treatments in SOD1G93A mice. In conclusion, Sig-1R ligands are promising tools for ALS treatment, although more research is needed to ascertain their mechanisms of action.

Effectiveness of Facilitation, Arrangement of Task and Situation, (Non-)verbal Communication, and Counseling of Caregivers in Children with Neuromotor Disorders: a Systematic Review

Objectives The techniques facilitation of activities, arrangement of task or situation, verbal and non-verbal communication, and counseling and empowerment of parents and caregivers are applied in different therapy approaches to improve motor function in children with neuromotor disorders. This review quantitatively examines the effectiveness of these four techniques allocated to pre-defined age groups and levels of disability. Methods We followed the systematic review methodology proposed by the American Academy for Cerebral Palsy and Developmental Medicine (AACPDM). The search was conducted on PubMed, Scopus, EMBASE, PEDro, OT Seeker, ERIC, and CINAHL. The main outcomes of the included articles were allocated to the framework of the International Classification of Functioning, Disability, and Health (body functions, activities, and participation). Results The search yielded eleven studies for facilitation, 22 for arrangement of task or situation, three for verbal and non-verbal communication, and three studies for counseling and empowerment. The effect sizes indicated strong evidence for body function and activity outcomes for the use of facilitation in newborns until the age of 2 years and the arrangement of tasks in children between 2 and 5 years with cerebral palsy. Conclusions Thus, while some evidence exist for facilitation and arrangement of task or situation, further research is needed on the effectiveness of verbal and non-verbal communication and counseling and empowerment of parents and caregivers to improve motor function, activities, and participation. Systematic review registration. PROSPERO CRD42017048583.

Effects of the Combination of Music Therapy and Physiotherapy in the Improvement of Motor Function in Cerebral Palsy: A Challenge for Research

Background: There are different therapeutic strategies such as physiotherapy and music therapy for the treatment of cerebral palsy. Intervention protocols using both therapies to unify the measurement of motor function have not been investigated. Aims and scope: To summarize the effects of the treatment of cerebral palsy through the use of both for the improvement of motor function, analyse the challenges encountered, and submit proposals for improving them. Methods: The systematic review was conducted following PRISMA guidelines and registered in the PROSPERO database (CRD42020162493). Clinical trials that described the results obtained in terms of motor function through physiotherapy and music therapy were included. Results: Eight clinical trials with 234 participants were considered with a significant improvement in motor function. Results of meta-analysis suggested improvements in gait velocity in favour of the control group for cerebral palsy (mean differences = 0.03; 95% confidence interval = 0.01, 0.04, p = 0.001; I2 = 97%). However, high heterogeneity was identified in the meta-analysis due to the small number of studies included. Conclusions: The combination can be effective in subjects with cerebral palsy to improve motor function, although due to the diversity of studies analysed, it is complex to extrapolate results.

Case Report: Visual Deprivation in Pusher Syndrome Complicated by Hemispatial Neglect After Basal Ganglia Stroke

We aimed to explore whether motor function and activities of daily life (ADL) could be improved with the application of visual deprivation in two patients with Pusher syndrome complicated by hemispatial neglect after right basal ganglia stroke. We assessed two stroke patients suffering from severe motor disturbances, both tilting heavily to the left, with diagnoses of Pusher syndrome and left hemispatial neglect. Vision in the left eye was deprived using patches during clinical rehabilitation. Motor function promotion was confirmed using the Burke Lateropulsion Scale (BLS), Fugl–Meyer Balance Scale (FMBS), and Holden grade (HG), while the Barthel index (BI) assessed ADL immediately and 1 week after intervention. Both patients regained standing balance immediately using visual deprivation, as well as walking ability, although both scored 0 on the FMBS and HG. After 1 week of treatment, one patient increased to 11 and 3 on the FMBS and HG, respectively, while the BLS score decreased from 12 to 2, and the ADL increased from 23 to 70. The other patient demonstrated increases to 10 and 3 on the FMBS and HG, respectively, with the BLS decreasing from 13 to 3, and the ADL increasing from 25 to 60. Therefore, in the rehabilitation treatment of Pusher syndrome complicated by hemispatial neglect due to basal ganglia stroke, visual deprivation can significantly improve motor function and shorten the treatment course.

Early intervention in obstetric brachial palsy: a review/ Intervenção precoce na paralisia braquial obstetrica: uma revisão

Obstetric brachial paralysis is the end of an injury to the nerve fibers of the brachial plexus during obstetric maneuvers during childbirth. The injury has a great impact on the functionality of the injured upper limb of the newborn. The signs and symptoms vary, depending on the location of the lesion. The early intervention of the physiotherapist in the rehabilitation process is essential to prevent complications and improve motor function. Physiotherapeutic treatment has a very important contribution to the rehabilitation of children with obstetric brachial palsy, however, it is important to respect the neuropsychomotor development process normal child. The physiotherapy objectives basically consists on avoiding contractures and adhesions; promoting motor and sensory stimulation; maintaining range of motion and functional training. Among the techniques that these professionals have, we can highlight passive and active kinesiotherapy, electrostimulation, proprioceptive stimulation, hydrotherapy and Movement Induction and Containment Therapy (MICT), always creating the best possible conditions for the recovery of this individual's functional capacity.

Cortical Re-organization After Traumatic Brain Injury Elicited Using Functional Electrical Stimulation Therapy: A Case Report

Functional electrical stimulation therapy (FEST) can improve motor function after neurological injuries. However, little is known about cortical changes after FEST and weather it can improve motor function after traumatic brain injury (TBI). Our study examined cortical changes and motor improvements in one male participant with chronic TBI suffering from mild motor impairment affecting the right upper-limb during 3-months of FEST and during 3-months follow-up. In total, 36 sessions of FEST were applied to enable upper-limb grasping and reaching movements. Short-term assessments carried out using transcranial magnetic stimulation (TMS) showed reduced cortical silent period (CSP), indicating cortical and/or subcortical inhibition after each intervention. At the same time, no changes in motor evoked potentials (MEPs) were observed. Long-term assessments showed increased MEP corticospinal excitability after 12-weeks of FEST, which seemed to remain during both follow-ups, while no changes in CSP were observed. Similarly, long-term assessments using TMS mapping showed larger hand MEP area in the primary motor cortex (M1) after 12-weeks of FEST as well as during both follow-ups. Corroborating TMS results, functional magnetic resonance imaging (fMRI) data showed M1 activations increased during hand grip and finger pinch tasks after 12-weeks of FEST, while gradual reduction of activity compared to after the intervention was seen during follow-ups. Widespread changes were seen not only in the M1, but also sensory, parietal rostroventral, supplementary motor, and premotor areas in both contralateral and ipsilateral hemispheres, especially during the finger pinch task. Drawing test performance showed improvements after the intervention and during follow-ups. Our findings suggest that task-specific and repetitive FEST can effectively increase cortical activations by integrating voluntary motor commands and sensorimotor network through functional electrical stimulation (FES). Overall, our results demonstrated cortical re-organization in an individual with chronic TBI after FEST.