Quantification of Upper Limb Motor Recovery and EEG Power Changes after Robot-Assisted Bilateral Arm Training in Chronic Stroke Patients: A Prospective Pilot Study.

Background: Bilateral arm training (BAT) has shown promise in expediting progress toward upper limb recovery in chronic stroke patients, but its neural correlates are poorly understood. Objective: To evaluate changes in upper limb function and EEG power after a robot-assisted BAT in chronic stroke patients. Methods: In a within-subject design, seven right-handed chronic stroke patients with upper limb paresis received 21 sessions (3 days/week) of the robot-assisted BAT. The outcomes were changes in score on the upper limb section of the Fugl-Meyer assessment (FM), Motricity Index (MI), and Modified Ashworth Scale (MAS) evaluated at the baseline (T0), posttraining (T1), and 1-month follow-up (T2). Event-related desynchronization/synchronization were calculated in the upper alpha and the beta frequency ranges. Results: Significant improvement in all outcomes was measured over the course of the study. Changes in FM were significant at T2, and in MAS at T1 and T2. After training, desynchronization on the ipsilesional sensorimotor areas increased during passive and active movement, as compared with T0. Conclusions: A repetitive robotic-assisted BAT program may improve upper limb motor function and reduce spasticity in the chronically impaired paretic arm. Effects on spasticity were associated with EEG changes over the ipsilesional sensorimotor network.

Prognostic Importance of Lesion Location on Functional Outcome in Patients with Cerebellar Ischemic Stroke: a Prospective Pilot Study.

To date, few studies focused on prediction of functional recovery after cerebellar stroke. The main aim of this prospective pilot study was to determine the association between cerebellar lesion location and functional outcome in adults with acute cerebellar infarction. We examined 14 patients with first-ever unilateral cerebellar ischemic stroke within 7 days and at 90 days from the onset of stroke by means of the International Cooperative Ataxia Rating Scale. Cerebellar lesions were traced from magnetic resonance imaging performed within 72 h since stroke and region of interest were generated. The association between the International Cooperative Ataxia Rating Scale score and lesion location was determined with the voxel-based lesion-symptom mapping methods implemented in the MRIcro software. Colored lesion-symptom maps representing the z statistics were generated and overlaid onto the MNI-ICBM 152 linear probabilistic atlas of the human brain and the Johns Hopkins University white matter templates. Our results documented that injuries to the V, VI, VIIA Crus I, VIIA Crus II, VIIB, VIIIA, and VIIIB lobules and the middle cerebellar peduncle are significantly associated with the International Cooperative Ataxia Rating Scale (ICARS) score at 1 week after the onset of stroke. Furthermore, we found that injuries to the VI, VIIA Crus I, VIIA Crus II, VIIB, VIIIA, and VIIIB lobules, the dentate nucleus, and the middle cerebellar peduncle are significantly associated with the ICARS score at 3 months since the cerebellar stroke onset. The findings of this pilot study might improve prognostic accuracy of functional outcome in patients with acute cerebellar infarction.

Sensory integration balance training in patients with multiple sclerosis: A randomized, controlled trial.

BACKGROUND: Impaired sensory integration contributes to balance disorders in patients with multiple sclerosis (MS). OBJECTIVE: The objective of this paper is to compare the effects of sensory integration balance training against conventional rehabilitation on balance disorders, the level of balance confidence perceived, quality of life, fatigue, frequency of falls, and sensory integration processing on a large sample of patients with MS. METHODS: This single-blind, randomized, controlled trial involved 80 outpatients with MS (EDSS: 1.5-6.0) and subjective symptoms of balance disorders. The experimental group (n = 39) received specific training to improve central integration of afferent sensory inputs; the control group (n = 41) received conventional rehabilitation (15 treatment sessions of 50 minutes each). Before, after treatment, and at one month post-treatment, patients were evaluated by a blinded rater using the Berg Balance Scale (BBS), Activities-specific Balance Confidence Scale (ABC), Multiple Sclerosis Quality of Life-54, Fatigue Severity Scale (FSS), number of falls and the Sensory Organization Balance Test (SOT). RESULTS: The experimental training program produced greater improvements than the control group training on the BBS (p < 0.001), the FSS (p < 0.002), number of falls (p = 0.002) and SOT (p < 0.05). CONCLUSIONS: Specific training to improve central integration of afferent sensory inputs may ameliorate balance disorders in patients with MS. Clinical Trial Registration (NCT01040117).

Robot-assisted gait training is not superior to balance training for improving postural instability in patients with mild to moderate Parkinson's disease: a single-blind randomized controlled trial.

OBJECTIVE: The main aim was to compare robotic gait training vs. balance training for reducing postural instability in patients with Parkinson's disease. The secondary aim was to compare their effects on the level of confidence during activities of daily living requiring balance, functional mobility and severity of disease. DESIGN: Randomized controlled trial. SETTING: University hospital. SUBJECTS: A total of 66 patients with Parkinson's disease at Hoehn and Yahr Stage 3. INTERVENTION: After balanced randomization, all patients received 12, 45-minute treatment sessions, three days a week, for four consecutive weeks. A group underwent robot-assisted gait training with progressive gait speed increasing and body-weight support decreasing. The other group underwent balance training aimed at improving postural reactions (self and externally induced destabilization, coordination, locomotor dexterity exercises). MAIN MEASURES: Patients were evaluated before, after and one month posttreatment. MAIN OUTCOME MEASURE: Berg Balance Scale. SECONDARY OUTCOMES: Activities-Specific Balance Confidence Scale; Timed Up and Go Test; Unified Parkinson's Disease Rating Scale. RESULTS: No significant differences were found between the groups for the Berg Balance Scale either immediately after intervention (mean score in the robotic training group 51.58 ±3.94; mean score in the balance training group 51.15 ±3.46), or one-month follow-up (mean score in the robotic training group 51.03 ±4.63; mean score in the balance training group 50.97 ±4.28). Similar results were found for all the secondary outcome measures. CONCLUSIONS: Our findings indicate that robotic gait training is not superior to balance training for improving postural instability in patients with mild to moderate Parkinson's disease.

Robot-assisted arm training in patients with Parkinson's disease: a pilot study.

BACKGROUND: Despite the growing diffusion of robotic devices in neurorehabilitation, no previous study investigated the effects of robotic training on arm impairment due to Parkinson's disease. The aim of this pilot study was to evaluate whether robot-assisted arm training might improve upper limb function in patients with Parkinson's disease. FINDINGS: Ten patients with Parkinson's disease (Hoehn and Yahr stage 2.5-3) received ten, 45-minute, treatment sessions, five days a week, for two consecutive weeks. Robot-assisted arm training was performed with the Bi-Manu-Track (Reha-Stim, Berlin, Germany) that provides a computer-controlled, repetitive, bilateral, mirror-like practice of forearm pronation/supination and wrist extension/flexion. Patients were trained according to the following modalities: passive-passive (both arms moved by the machine) and active-active (both arms actively moving against resistance). The dominant upper limb was evaluated before and immediately after treatment as well as at two weeks of follow-up. Outcomes were the nine-hole peg test, the Fugl-Meyer assessment (upper limb section) and the Unified Parkinson's Disease Rating Scale. After treatment, a significant improvement was found in the nine-hole peg test (P = 0.007) as well as in the upper limb section of the Fugl-Meyer assessment (P = 0.012). Findings were confirmed at the 2-week follow-up evaluation only for the nine-hole peg test (P = 0.007). No significant improvement was found in the Unified Parkinson's Disease Rating Scale at both post-treatment and follow-up evaluations. CONCLUSIONS: Our findings support the hypothesis that robot-assisted arm training might be a promising tool in order to improve upper limb function in patients with Parkinson's disease.

Effects of upper limb vibratory stimulation training on motor symptoms in Parkinson's disease: an observational study.

OBJECTIVES: Parkinson's disease is characterized by motor and non-motor symptoms. Tremor is one of the motor symptoms that can affect manual skills and have an impact on daily activities. The aim of the current study is to investigate the effect of upper limb training provided by a specific vibratory device (Armshake®, Move It GmbH - Bochum, Germany) on tremor and motor functionality in patients with Parkinson's disease. Furthermore, the training effect on global cognitive functioning is assessed. DESIGN: An uncontrolled before-after clinical trial. PATIENTS: Individuals with diagnosis of Parkinson's disease, motor upper limbs deficits, and absence of dementia. METHODS: Participants underwent a 3-week programme (3 times a week) and was evaluated before, after, and at 1 month follow-up by motor (Fahn Tolosa Marin Tremor Rating Scale, Unified Parkinson's Disease Rating Scale - part III, Purdue Pegboard Test, Disability of the Arm, Shoulder and Hand Questionnaire) and cognitive (Montreal Cognitive Assessment) scales. RESULTS: Twenty subjects are included. After treatment a statistically significant improvement in tremor, manual dexterity and activities of daily living was found. The data indicated no effects on global cognitive functioning. CONCLUSION: These findings suggest positive effects of vibratory stimulation training on upper limb motor symptoms in Parkinson's disease.

Modulation of event-related desynchronization in robot-assisted hand performance: brain oscillatory changes in active, passive and imagined movements.

BACKGROUND: Robot-assisted therapy in patients with neurological disease is an attempt to improve function in a moderate to severe hemiparetic arm. A better understanding of cortical modifications after robot-assisted training could aid in refining rehabilitation therapy protocols for stroke patients. Modifications of cortical activity in healthy subjects were evaluated during voluntary active movement, passive robot-assisted motor movement, and motor imagery tasks performed under unimanual and bimanual protocols. METHODS: Twenty-one channel electroencephalography (EEG) was recorded with a video EEG system in 8 subjects. The subjects performed robot-assisted tasks using the Bi-Manu Track robot-assisted arm trainer. The motor paradigm was executed during one-day experimental sessions under eleven unimanual and bimanual protocols of active, passive and imaged movements. The event-related-synchronization/desynchronization (ERS/ERD) approach to the EEG data was applied to investigate where movement-related decreases in alpha and beta power were localized. RESULTS: Voluntary active unilateral hand movement was observed to significantly activate the contralateral side; however, bilateral activation was noted in all subjects on both the unilateral and bilateral active tasks, as well as desynchronization of alpha and beta brain oscillations during the passive robot-assisted motor tasks. During active-passive movement when the right hand drove the left one, there was predominant activation in the contralateral side. Conversely, when the left hand drove the right one, activation was bilateral, especially in the alpha range. Finally, significant contralateral EEG desynchronization was observed during the unilateral task and bilateral ERD during the bimanual task. CONCLUSIONS: This study suggests new perspectives for the assessment of patients with neurological disease. The findings may be relevant for defining a baseline for future studies investigating the neural correlates of behavioral changes after robot-assisted training in stroke patients.

Robotic versus Conventional Overground Gait Training in Subacute Stroke Survivors: A Multicenter Controlled Clinical Trial.

BACKGROUND: Although stroke survivors can benefit from robotic gait rehabilitation, stationary robot-assisted gait training needs further investigation. In this paper, we investigated the efficacy of this approach (with an exoskeleton or an end-effector robot) in comparison to the conventional overground gait training in subacute stroke survivors. METHODS: In a multicenter controlled clinical trial, 89 subacute stroke survivors conducted twenty sessions of robot-assisted gait training (Robotic Group) or overground gait training (Control Group) in addition to the standard daily therapy. The robotic training was performed with an exoskeleton (RobotEXO-group) or an end-effector (RobotEND-group). Clinical outcomes were assessed before (T0) and after (T1) the treatment. The walking speed during the 10-Meter Walk Test (10 MWT) was the primary outcome of this study, and secondary outcomes were the 6-Minute Walk Test (6 MWT), Timed Up and Go test (TUG), and the modified Barthel Index (mBI). RESULTS: The main characteristics assessed in the Robotic and Control groups did not differ at baseline. A significant benefit was detected from the 10 MWT in the Robotic Group at the end of the study period (primary endpoint). A benefit was also observed from the following parameters: 6 MWT, TUG, and mBI. Moreover, patients belonging to the Robot Group outperformed the Control Group in gait speed, endurance, balance, and ADL. The RobotEND-group improved their walking speed more than the RobotEXO-group. CONCLUSION: The stationary robot-assisted training improved walking ability better than the conventional training in subacute stroke survivors. These results suggest that people with subacute stroke may benefit from Robot-Assisted training in potentiating gait speed and endurance. Our results also support that end-effector robots would be superior to exoskeleton robots for improving gait speed enhancement.

Effect of Upper Limb Motor Rehabilitation on Cognition in Parkinson's Disease: An Observational Study.

Parkinson's disease is characterized by motor and cognitive deficits that usually have an impact on quality of life and independence. To reduce impairment, various rehabilitation programs have been proposed, but their effects on both cognitive and motor aspects have not been systematically investigated. Furthermore, most intervention is focused on lower limb treatment rather than upper limbs. In the present study, we investigated the effect of 3-week upper limb vibratory stimulation training on cognitive functioning in 20 individuals with Parkinson's disease. We analyzed cognitive (Montreal Cognitive Assessment, Trial Making Test, Digit Symbol, Digit Span Forward and Backward and Alertness) and motor performance (Unified Parkinson's Disease Rating Scale-part III; Disability of the Arm, Shoulder and Hand Questionnaire) before treatment, at the end of treatment and one month post treatment. After rehabilitation, a statistically significant improvement was observed in terms of global cognitive status, attention, global motor functioning and disability. The results suggest an impact of upper limb motor rehabilitation on cognition in Parkinson's disease. Future studies on neuromotor interventions should investigate their effects on cognitive functioning to improve understanding of cognitive motor interaction in Parkinson's disease.

External lid loading for the temporary treatment of paresis of the M. orbicularis oculi: a case report.

This clinical note re-introduces external lid loading with the help of a lead weight for the temporary treatment of lagophthalmos. Although simple and effective, the technique is rarely used. Instead of wearing a monoculus, the patient uses an individually tailored lead weight (0.8-mm thickness, 1.0-2.0g) stuck on the lid to enable its closure. Spontaneous ptosis indicates a too-heavy weight. With the musculus (M.) levator palpebrae intact, lid lifting is possible. The effect is gravity dependent; therefore, the patient has to wear the monoculus at night. To minimize the risk for lead intoxication, the surface of the weight is varnished. In the case of persistent M. orbicularis oculi paresis, internal lid loading can follow. Since 1997, a total of 152 lagophthalmos cases have been treated. All patients could close the lid immediately. Almost half the patients had to readjust the weight several times per day because of hooded eyelids. Compliance was high, and partial or complete restoration of M. orbicularis oculi function occurred in 60% of cases. In some subjects, restoration of the M. orbicularis oculi was faster than for the M. orbicularis orbis. External lid loading for the temporary treatment of lagophthalmos is simple and effective. Compared with a monoculus, vision is unimpaired and the aesthetic is more appropriate for most patients. Faster restoration of the M. orbicularis oculi hints at a potentially facilitatory effect of the weight.

Combined transcranial direct current stimulation and robot-assisted gait training in patients with chronic stroke: a preliminary comparison.

OBJECTIVE: To evaluate whether robot-assisted gait training combined with transcranial direct current stimulation is more effective than robot-assisted gait training alone or conventional walking rehabilitation for improving walking ability in stroke patients. DESIGN: Pilot randomized clinical trial. SETTING: Rehabilitation unit of a university hospital. SUBJECTS: Thirty patients with chronic stroke. INTERVENTIONS: All patients received ten 50-minute treatment sessions, five days a week, for two consecutive weeks. Group 1 (n = 10) underwent a robot-assisted gait training combined with transcranial direct current stimulation; group 2 (n = 10) underwent a robot-assisted gait training combined with sham transcranial direct current stimulation; group 3 (n = 10) performed overground walking exercises. MAIN MEASURES: Patients were evaluated before, immediately after and two weeks post treatment. PRIMARY OUTCOMES: six-minute walking test, 10-m walking test. RESULTS: No differences were found between groups 1 and 2 for all primary outcome measures at the after treatment and follow-up evaluations. A statistically significant improvement was found after treatment in performance on the six-minute walking test and the 10-m walking test in favour of group 1 (six-minute walking test: 205.20 ± 61.16 m; 10-m walking test: 16.20 ± 7.65 s) and group 2 (six-minute walking test: 182.5 ± 69.30 m; 10-m walking test: 17.71 ± 8.20 s) compared with group 3 (six-minute walking test: 116.30 ± 75.40 m; 10-m walking test: 26.30 ± 14.10 s). All improvements were maintained at the follow-up evaluation. CONCLUSIONS: In the present pilot study transcranial direct current stimulation had no additional effect on robot-assisted gait training in patients with chronic stroke. Larger studies are required to confirm these preliminary findings.

Celecoxib promotes survival and upregulates the expression of neuroprotective marker genes in two different in vitro models of Parkinson's disease.

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder after Alzheimer's disease. Increasing evidence highlights the role of age-related chronic inflammation, oxidative stress and mitochondrial dysfunction in the pathogenesis of PD. A combination of these factors impairs the crosstalk between mitochondria and lysosomes, resulting in compromised cell homeostasis. Apolipoprotein D (APOD), an ancient and highly conserved anti-inflammatory and antioxidant lipocalin, and the transcription factor EB (TFEB), a master regulator of mitophagy, autophagy and lysosomal biogenesis, play key roles in these processes. Both APOD and TFEB have attracted attention as therapeutic targets for PD. The aim of this study was to investigate if the selective cyclooxygenase-2 inhibitor celecoxib (CXB) exerts a direct neuroprotective effect in 6-hydroxydopamine (6-OHDA) and paraquat (PQ) PD models. We found that CXB rescued SH-SY5Y cells challenged by 6-OHDA- and PQ-induced toxicity. Furthermore, treatment with CXB led to a marked and sustained upregulation of APOD and the two microphthalmia transcription factors TFEB and MITF. In sum, this study highlights the clinically approved drug CXB as a promising neuroprotective therapeutic tool in PD research that has the potential to increase the survival rate of dopaminergic neurons that are still alive at the time of diagnosis.

Innovative gait robot for the repetitive practice of floor walking and stair climbing up and down in stroke patients.

BACKGROUND: Stair climbing up and down is an essential part of everyday's mobility. To enable wheelchair-dependent patients the repetitive practice of this task, a novel gait robot, G-EO-Systems (EO, Lat: I walk), based on the end-effector principle, has been designed. The trajectories of the foot plates are freely programmable enabling not only the practice of simulated floor walking but also stair climbing up and down. The article intended to compare lower limb muscle activation patterns of hemiparetic subjects during real floor walking and stairs climbing up, and during the corresponding simulated conditions on the machine, and secondly to demonstrate gait improvement on single case after training on the machine. METHODS: The muscle activation pattern of seven lower limb muscles of six hemiparetic patients during free and simulated walking on the floor and stair climbing was measured via dynamic electromyography. A non-ambulatory, sub-acute stroke patient additionally trained on the G-EO-Systems every workday for five weeks. RESULTS: The muscle activation patterns were comparable during the real and simulated conditions, both on the floor and during stair climbing up. Minor differences, concerning the real and simulated floor walking conditions, were a delayed (prolonged) onset (duration) of the thigh muscle activation on the machine across all subjects. Concerning stair climbing conditions, the shank muscle activation was more phasic and timely correct in selected patients on the device. The severely affected subject regained walking and stair climbing ability. CONCLUSIONS: The G-EO-Systems is an interesting new option in gait rehabilitation after stroke. The lower limb muscle activation patterns were comparable, a training thus feasible, and the positive case report warrants further clinical studies.

Transfer of scientific concepts to clinical practice: recent robot-assisted training studies.

Restoration of motor function is a priority of post-stroke rehabilitation, the aim being to facilitate the patient's reintegration into society. Innovative technologies for neurological rehabilitation must be easy to use and offer patients real benefits, and the treatments they provide must be efficacious and efficient. All these aspects must be carefully evaluated in their development. To achieve restoration of motor function after stroke, task-specific repetitive robot-assisted training of the upper and the lower extremity is currently the most promising approach. The results of clinical trials of robotic devices for upper limb (MIT-Manus, MIME, NeReBot, BiManuTrack, ARMin, ARMOR) and lower limb (LokoHelp, GangTrainer GT1, Haptic Walker, G-EO-Systems, Lokomat) training are here presented with the aim of highlighting the possible gains in motor function due to robotic therapy. Patients who receive robot-assisted training in combination with physiotherapy after stroke are more likely to achieve better motor function than patients trained without these devices, or only with these devices.

Effects of two different protocols of cerebellar transcranial direct current stimulation combined with transcutaneous spinal direct current stimulation on robot-assisted gait training in patients with chronic supratentorial stroke: A single blind, randomized controlled trial.

BACKGROUND: The neural organization of locomotion involves motor patterns generated by spinal interneuronal networks and supraspinal structures, which are approachable by noninvasive stimulation techniques. Recent evidences supported the hypothesis that transcranial direct current stimulation (combined with transcutaneous spinal direct current stimulation) may actually enhance the effects of robot-assisted gait training in chronic stroke patients. The cerebellum has many connections to interact with neocortical areas and may provide some peculiar plasticity mechanisms. So, it has been proposed as "non-lesioned entry" to the motor or cognitive system for the application of noninvasive stimulation techniques in patients with supratentorial stroke. OBJECTIVE: To compare the effects of two different protocols of cerebellar transcranial direct current stimulation combined with transcutaneous spinal direct current stimulation on robotic gait training in patients with chronic supratentorial stroke. METHODS: Forty patients with chronic supratentorial stroke were randomly assigned into two groups. All patients received ten, 20-minute robotic gait training sessions, five days a week, for two consecutive weeks. Group 1 underwent cathodal transcranial direct current stimulation over the contralesional cerebellar hemisphere + cathodal transcutaneous spinal direct current stimulation in combination with robotic training. Group 2 underwent cathodal transcranial direct current stimulation over the ipsilesional cerebellar hemisphere + cathodal transcutaneous spinal direct current stimulation in combination with robotic training. The primary outcome was the 6-minute walk test performed before, after, and at follow-up at 2 and 4 weeks post-treatment. RESULTS: No significant difference in the 6-minute walk test between groups was found at the first post-treatment evaluation (P = 0.976), as well as at the 2-week (P = 0.178) and the 4-week (P = 0.069) follow-up evaluations. Both groups showed significant within-group improvements in the 6-minute walk test at all time points.∥Conclusions: Our findings support the hypothesis that cathodal transcranial direct current stimulation over the contralesional or ipsilesional cerebellar hemisphere in combination with cathodal transcutaneous spinal direct current stimulation may lead to similar effects on robotic gait training in chronic supratentorial stroke patients.

Robot-Assisted Stair Climbing Training on Postural Control and Sensory Integration Processes in Chronic Post-stroke Patients: A Randomized Controlled Clinical Trial.

BACKGROUND: Postural control disturbances are one of the important causes of disability in stroke patients affecting balance and mobility. The impairment of sensory input integration from visual, somatosensory and vestibular systems contributes to postural control disorders in post-stroke patients. Robot-assisted gait training may be considered a valuable tool in improving gait and postural control abnormalities. OBJECTIVE: The primary aim of the study was to compare the effects of robot-assisted stair climbing training against sensory integration balance training on static and dynamic balance in chronic stroke patients. The secondary aims were to compare the training effects on sensory integration processes and mobility. METHODS: This single-blind, randomized, controlled trial involved 32 chronic stroke outpatients with postural instability. The experimental group (EG, n = 16) received robot-assisted stair climbing training. The control group (n = 16) received sensory integration balance training. Training protocols lasted for 5 weeks (50 min/session, two sessions/week). Before, after, and at 1-month follow-up, a blinded rater evaluated patients using a comprehensive test battery. Primary outcome: Berg Balance Scale (BBS). Secondary outcomes:10-meter walking test, 6-min walking test, Dynamic gait index (DGI), stair climbing test (SCT) up and down, the Time Up and Go, and length of sway and sway area of the Center of Pressure (CoP) assessed using the stabilometric assessment. RESULTS: There was a non-significant main effect of group on primary and secondary outcomes. A significant Time × Group interaction was measured on 6-min walking test (p = 0.013) and on posturographic outcomes (p = 0.005). Post hoc within-group analysis showed only in the EG a significant reduction of sway area and the CoP length on compliant surface in the eyes-closed and dome conditions. CONCLUSION: Postural control disorders in patients with chronic stroke may be ameliorated by robot-assisted stair climbing training and sensory integration balance training. The robot-assisted stair climbing training contributed to improving sensorimotor integration processes on compliant surfaces. Clinical trial registration (NCT03566901).

Characterization of Upper Limb Impairments at Body Function, Activity, and Participation in Persons With Multiple Sclerosis by Behavioral and EMG Assessment: A Cross-Sectional Study.

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and disabling disease which primarily affects individuals in their early life between 20 and 40 years of age. MS is a complex condition, which may lead to a variety of upper limb (UL) dysfunctions and functional deficits. Objective: To explore upper limb impairments at body function, activity, and participation in persons with MS (PwMS) and severe hand dexterity impairment by behavioral and surface electromyography (sEMG) assessments. Methods: This observational cross-sectional study involved 41 PwMS with severe hand dexterity impairment stratified according to the Expanded Disability Status Scale (EDSS) into mild-moderate (n = 17; EDSS, 1-5.5), severe ambulant (n = 15; EDSS, 6-6.5), and severe nonambulant (n = 9; EDSS, 7-9.5). Behavioral outcome measures exploring body function, activity, and participation were administered. The sEMG activity of six upper limb muscles of the most affected side was measured during a reaching task. Results: The most severe group was significantly older and more affected by secondary progressive MS than the other two groups. Positive significant associations between UL deterioration and impairments at different International Classification of Functioning, Disability, and Health domains were noted in the most severe group. The progressive decline in manual dexterity was moderately to strongly associated with the deterioration of the overall UL activity (ρ = 0.72; p < 0.001) and disuse (amount of use ρ = 0.71; p < 0.001; quality of movement ρ = 0.77; p < 0.001). There was a low correlation between manual dexterity and UL function (ρ = 0.33; p = 0.03). The muscle activation pattern investigated by sEMG was characterized by a decrease in modularity and timing delay in the wrist extensor muscles activation in the severe ambulant patients (EDSS, 6-6.5). Similar impairments were observed in the proximal muscles (anterior deltoid) in the more advanced stages (EDSS ≥ 7). Conclusion: Behavioral assessment, together with measures of muscle activation patterns, allows investigating the pathophysiology of UL impairments in PwMS across progressive neurological disability severity to implement task-specific rehabilitation interventions.

Apolipoprotein D Concentration in Human Plasma during Aging and in Parkinson's Disease: A Cross-Sectional Study.

Apolipoprotein D (ApoD), a lipocalin transporter of small hydrophobic molecules, plays an important role in several neurodegenerative diseases. ApoD is expressed in and secreted from a variety of peripheral and brain tissues. Increments of ApoD have been reported in relation with oxidative stress conditions, aging, and degeneration in the nervous system. Preliminary findings support the role of ApoD in neuroprotection. However, its role in PD remains unclear. To date, no studies have been performed on the relationship between ApoD in the blood and PD, as neurodegenerative pathology related to oxidative damage. We investigated the concentration of ApoD in the blood of healthy control subjects and PD patients with mild-to-moderate neurological impairment. ApoD plasma levels were measured using sandwich enzyme-linked immunosorbent assays (ELISA) in 90 healthy subjects (aging-analysis cohort) and in 66 PD patients at different stages compared with 19 age-matched healthy subjects. Significant age-related increase of ApoD was detected in subjects older than 65 years of age (p < 0.002). In PD patients, a significant increase in ApoD plasma concentration was found compared with healthy subjects of the same age (p < 0.05). ApoD and PD stage are significantly correlated (p < 0.05). ApoD might be a valid marker for the progression of PD.

Combined effects of cerebellar transcranial direct current stimulation and transcutaneous spinal direct current stimulation on robot-assisted gait training in patients with chronic brain stroke: A pilot, single blind, randomized controlled trial.

BACKGROUND: Preliminary evidence showed additional effects of anodal transcranial direct current stimulation over the damaged cerebral hemisphere combined with cathodal transcutaneous spinal direct current stimulation during robot-assisted gait training in chronic stroke patients. This is consistent with the neural organization of locomotion involving cortical and spinal control. The cerebellum is crucial for locomotor control, in particular for avoidance of obstacles, and adaptation to novel conditions during walking. Despite its key role in gait control, to date the effects of transcranial direct current stimulation of the cerebellum have not been investigated on brain stroke patients treated with robot-assisted gait training. OBJECTIVE: To evaluate the effects of cerebellar transcranial direct current stimulation combined with transcutaneous spinal direct current stimulation on robot-assisted gait training in patients with chronic brain stroke. METHODS: After balanced randomization, 20 chronic stroke patients received ten, 20-minute robot-assisted gait training sessions (five days a week, for two consecutive weeks) combined with central nervous system stimulation. Group 1 underwent on-line cathodal transcranial direct current stimulation over the contralesional cerebellar hemisphere + cathodal transcutaneous spinal direct current stimulation. Group 2 received on-line anodal transcranial direct current stimulation over the damaged cerebral hemisphere + cathodal transcutaneous spinal direct current stimulation. The primary outcome was the 6-minute walk test performed before, after, and at follow-up at 2 and 4 weeks post-treatment. RESULTS: The significant differences in the 6-minute walk test noted between groups at the first post-treatment evaluation (p = 0.041) were not maintained at either the 2-week (P = 0.650) or the 4-week (P = 0.545) follow-up evaluations. CONCLUSION: Our preliminary findings support the hypothesis that cathodal transcranial direct current stimulation over the contralesional cerebellar hemisphere in combination with cathodal transcutaneous spinal direct current stimulation might be useful to boost the effects of robot-assisted gait training in chronic brain stroke patients with walking impairment.

Effects of High-intensity Robot-assisted Hand Training on Upper Limb Recovery and Muscle Activity in Individuals With Multiple Sclerosis: A Randomized, Controlled, Single-Blinded Trial.

Background : Integration of robotics and upper limb rehabilitation in people with multiple sclerosis (PwMS) has rarely been investigated. Objective: To compare the effects of robot-assisted hand training against non-robotic hand training on upper limb activity in PwMS. To compare the training effects on hand dexterity, muscle activity, and upper limb dysfunction as measured with the International Classification of Functioning. Methods: This single-blind, randomized, controlled trial involved 44 PwMS (Expanded Disability Status Scale:1.5-8) and hand dexterity deficits. The experimental group (n = 23) received robot-assisted hand training; the control group (n = 21) received non-robotic hand training. Training protocols lasted for 5 weeks (50 min/session, 2 sessions/week). Before (T0), after (T1), and at 1 month follow-up (T2), a blinded rater evaluated patients using a comprehensive test battery. Primary outcome: Action Research Arm Test. Secondary outcomes: Nine Holes Peg Test; Fugl-Meyer Assessment Scale-upper extremity section; Motricity Index; Motor Activity Log; Multiple Sclerosis (MS) Quality of Life-54; Life Habits assessment-general short form and surface electromyography. Results: There were no significant between-group differences in primary and secondary outcomes. Electromyography showed relevant changes providing evidence increased activity in the extensor carpi at T1 and T2. Conclusion: The training effects on upper limb activity and function were comparable between the two groups. However, robot-assisted training demonstrated remarkable effects on upper limb use and muscle activity. https://clinicaltrials.gov NCT03561155.