Neurophysiological underpinnings of an intensive protocol for upper limb motor recovery in subacute and chronic stroke patients.

BACKGROUND: Upper limb (UL) motor impairment following stroke is a leading cause of functional limitations in activities of daily living. Robot-assisted therapy supports rehabilitation, but how its efficacy and the underlying neural mechanisms depend on the time after stroke is yet to be assessed. AIM: We investigated the response to an intensive protocol of robot-assisted rehabilitation in sub-acute and chronic stroke patients, by analyzing the underlying changes in clinical scores, electroencephalography (EEG) and end-effector kinematics. We aimed at identifying neural correlates of the participants' upper limb motor function recovery, following an intensive 2-week rehabilitation protocol. DESIGN: Prospective cohort study. SETTING: Inpatients and outpatients from the Neurorehabilitation Unit of Pisa University Hospital, Italy. POPULATION: Sub-acute and chronic stroke survivors. METHODS: Thirty-one stroke survivors (14 sub-acute, 17 chronic) with mild-to-moderate UL paresis were enrolled. All participants underwent ten rehabilitative sessions of task-oriented exercises with a planar end-effector robotic device. All patients were evaluated with the Fugl-Meyer Assessment Scale and the Wolf Motor Function Test, at recruitment (T0), end-of-treatment (T1), and one-month follow-up (T2). Along with clinical scales, kinematic parameters and quantitative EEG were collected for each patient. Kinematics metrics were related to velocity, acceleration and smoothness of the movement. Relative power in four frequency bands was extracted from the EEG signals. The evolution over time of kinematic and EEG features was analyzed, in correlation with motor recovery. RESULTS: Both groups displayed significant gains in motility after treatment. Sub-acute patients displayed more pronounced clinical improvements, significant changes in kinematic parameters, and a larger increase in Beta-band in the motor area of the affected hemisphere. In both groups these improvements were associated to a decrease in the Delta-band of both hemispheres. Improvements were retained at T2. CONCLUSIONS: The intensive two-week rehabilitation protocol was effective in both chronic and sub-acute patients, and improvements in the two groups shared similar dynamics. However, stronger cortical and behavioral changes were observed in sub-acute patients suggesting different reorganizational patterns. CLINICAL REHABILITATION IMPACT: This study paves the way to personalized approaches to UL motor rehabilitation after stroke, as highlighted by different neurophysiological modifications following recovery in subacute and chronic stroke patients.

Cortico-muscular connectivity is modulated by passive and active Lokomat-assisted Gait.

The effects of robotic-assisted gait (RAG) training, besides conventional therapy, on neuroplasticity mechanisms and cortical integration in locomotion are still uncertain. To advance our knowledge on the matter, we determined the involvement of motor cortical areas in the control of muscle activity in healthy subjects, during RAG with Lokomat, both with maximal guidance force (100 GF-passive RAG) and without guidance force (0 GF-active RAG) as customary in rehabilitation treatments. We applied a novel cortico-muscular connectivity estimation procedure, based on Partial Directed Coherence, to jointly study source localized EEG and EMG activity during rest (standing) and active/passive RAG. We found greater cortico-cortical connectivity, with higher path length and tendency toward segregation during rest than in both RAG conditions, for all frequency bands except for delta. We also found higher cortico-muscular connectivity in distal muscles during swing (0 GF), and stance (100 GF), highlighting the importance of direct supraspinal control to maintain balance, even when gait is supported by a robotic exoskeleton. Source-localized connectivity shows that this control is driven mainly by the parietal and frontal lobes. The involvement of many cortical areas also in passive RAG (100 GF) justifies the use of the 100 GF RAG training for neurorehabilitation, with the aim of enhancing cortical-muscle connections and driving neural plasticity in neurological patients.

Clinical efficacy of botulinum toxin type A in patients with traumatic brain injury, spinal cord injury, or multiple sclerosis: An observational longitudinal study.

Botulinum toxin type A (BoNT-A) is the treatment of choice for focal spasticity, with a concomitant effect on pain reduction and improvement of quality of life (QoL). Current evidence of its efficacy is based mainly on post stroke spasticity. This study aims to clarify the role of BoNT-A in the context of non-stroke spasticity (NSS). We enrolled 86 patients affected by multiple sclerosis, spinal cord injury, and traumatic brain injury with clinical indication to perform BoNT-A treatment. Subjects were evaluated before injection and after 1, 3, and 6 months. At every visit, spasticity severity using the modified Ashworth scale, pain using the numeric rating scale, QoL using the Euro Qol Group EQ-5D-5L, and the perceived treatment effect using the Global Assessment of Efficacy scale were recorded. In our population BoNT-A demonstrated to have a significant effect in improving all the outcome variables, with different effect persistence over time in relation to the diagnosis and the number of treated sites. Our results support BoNT-A as a modifier of the disability condition and suggest its implementation in the treatment of NSS, delivering a possible starting point to generate diagnosis-specific follow-up programs. Clinical trial identifier: NCT04673240.

Evidence-based improvement of gait in post-stroke patients following robot-assisted training: A systematic review.

BACKGROUND: The recovery of walking after stroke is a priority goal for recovering autonomy. In the last years robotic systems employed for Robotic Assisted Gait Training (RAGT) were developed. However, literature and clinical practice did not offer standardized RAGT protocol or pattern of evaluation scales. OBJECTIVE: This systematic review aimed to summarize the available evidence on the use of RAGT in post-stroke, following the CICERONE Consensus indications. METHODS: The literature search was conducted on PubMed, Cochrane Library and PEDro, including studies with the following criteria: 1) adult post-stroke survivors with gait disability in acute/subacute/chronic phase; 2) RAGT as intervention; 3) any comparators; 4) outcome regarding impairment, activity, and participation; 5) both primary studies and reviews. RESULTS: Sixty-one articles were selected. Data about characteristics of patients, level of disability, robotic devices used, RAGT protocols, outcome measures, and level of evidence were extracted. CONCLUSION: It is possible to identify robotic devices that are more suitable for specific phase disease and level of disability, but we identified significant variability in dose and protocols. RAGT as an add-on treatment seemed to be prevalent. Further studies are needed to investigate the outcomes achieved as a function of RAGT doses delivered.

Gait robot-assisted rehabilitation in persons with spinal cord injury: A scoping review.

BACKGROUND: Many robots are available for gait rehabilitation (BWSTRT and ORET) and their application in persons with SCI allowed an improvement of walking function. OBJECTIVE: The aim of the study is to compare the effects of different robotic exoskeletons gait training in persons with different SCI level and severity. METHODS: Sixty-two studies were included in this systematic review; the study quality was assessed according to GRADE and PEDro's scale. RESULTS: Quality assessment of included studies (n = 62) demonstrated a prevalence of evidence level 2; the quality of the studies was higher for BWSTRT (excellent and good) than for ORET (fair and good). Almost all persons recruited for BWSTRT had an incomplete SCI; both complete and incomplete SCI were recruited for ORET. The SCI lesion level in the persons recruited for BWSTRT are from cervical to sacral; mainly from thoracic to sacral for ORET; a high representation of AIS D lesion resulted both for BWSTRT (30%) and for ORET (45%). The walking performance, tested with 10MWT, 6MWT, TUG and WISCI, improved after exoskeleton training in persons with incomplete SCI lesions, when at least 20 sessions were applied. Persons with complete SCI lesions improved the dexterity in walking with exoskeleton, but did not recover independent walking function; symptoms such as spasticity, pain and cardiovascular endurance improved. CONCLUSION: Different exoskeletons are available for walking rehabilitation in persons with SCI. The choice about the kind of robotic gait training should be addressed on the basis of the lesion severity and the possible comorbidities.

Robot-assisted gait training in patients with Parkinson's disease: Implications for clinical practice. A systematic review.

BACKGROUND: Gait impairments are common disabling symptoms of Parkinson's disease (PD). Among the approaches for gait rehabilitation, interest in robotic devices has grown in recent years. However, the effectiveness compared to other interventions, the optimum amount of training, the type of device, and which patients might benefit most remains unclear. OBJECTIVE: To conduct a systematic review about the effects on gait of robot-assisted gait training (RAGT) in PD patients and to provide advice for clinical practice. METHODS: A search was performed on PubMed, Scopus, PEDro, Cochrane library, Web of science, and guideline databases, following PRISMA guidelines. We included English articles if they used a robotic system with details about the intervention, the parameters, and the outcome measures. We evaluated the level and quality of evidence. RESULTS: We included twenty papers out of 230 results: two systematic reviews, 9 randomized controlled trials, 4 uncontrolled studies, and 5 descriptive reports. Nine studies used an exoskeleton device and the remainders end-effector robots, with large variability in terms of subjects' disease-related disability. CONCLUSIONS: RAGT showed benefits on gait and no adverse events were recorded. However, it does not seem superior to other interventions, except in patients with more severe symptoms and advanced disease.

What does evidence tell us about the use of gait robotic devices in patients with multiple sclerosis? A comprehensive systematic review on functional outcomes and clinical recommendations.

INTRODUCTION: There is growing evidence on the efficacy of gait robotic rehabilitation in patients with multiple sclerosis (MS), but most of the studies have focused on gait parameters. Moreover, clear indications on the clinical use of robotics still lack. As part of the CICERONE Italian Consensus on Robotic Rehabilitation, the aim of this systematic review was to investigate the existing evidence concerning the role of lower limb robotic rehabilitation in improving functional recovery in patients with MS. EVIDENCE ACQUISITION: We searched for and systematically reviewed evidence-based studies on gait robotic rehabilitation in MS, between January 1st, 2010 and December 31st, 2020, in the following databases: Cochrane Library, PEDro, PubMed and Google Scholar. The study quality was assessed by the 16-item assessment of multiple systematic reviews 2 (AMSTAR 2) and the 10-item PEDro scale for the other research studies. EVIDENCE SYNTHESIS: After an accurate screening, only 17 papers were included in the review, and most of them (13 RCT) had a level II evidence. Most of the studies used the Lokomat as a grounded robotic device, two investigated the efficacy of end-effectors and two powered exoskeletons. Generally speaking, robotic treatment has beneficial effects on gait speed, endurance and balance with comparable outcomes to those of conventional treatments. However, in more severe patients (EDSS >6), robotics leads to better functional outcomes. Notably, after gait training with robotics (especially when coupled to virtual reality) MS patients also reach better non-motor outcomes, including spasticity, fatigue, pain, psychological well-being and quality of life. Unfortunately, no clinical indications emerge on the treatment protocols. CONCLUSIONS: The present comprehensive systematic review highlights the potential beneficial role on functional outcomes of the lower limb robotic devices in people with MS. Future studies are warranted to evaluate the role of robotics not only for walking and balance outcomes, but also for other gait-training-related benefits, to identify appropriate outcome measures related to a specific subgroup of MS subjects' disease severity.

Robotic-assisted gait rehabilitation following stroke: a systematic review of current guidelines and practical clinical recommendations.

INTRODUCTION: Stroke is the third leading cause of adult disability worldwide, and lower extremity motor impairment is one of the major determinants of long-term disability. Although robotic therapy is becoming more and more utilized in research protocols for lower limb stroke rehabilitation, the gap between research evidence and its use in clinical practice is still significant. The aim of this study was to determine the scope, quality, and consistency of guidelines for robotic lower limb rehabilitation after stroke, in order to provide clinical recommendations. EVIDENCE ACQUISITION: We systematically reviewed stroke rehabilitation guideline recommendations between January 1, 2010 and October 31, 2020. We explored electronic databases (N.=4), guideline repositories and professional rehabilitation networks (N.=12). Two independent reviewers used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, and brief syntheses were used to evaluate and compare the different recommendations, considering only the most recent version. EVIDENCE SYNTHESIS: From the 1219 papers screened, ten eligible guidelines were identified from seven different regions/countries. Four of the included guidelines focused on stroke management, the other six on stroke rehabilitation. Robotic rehabilitation is generally recommended to improve lower limb motor function, including gait and strength. Unfortunately, there is still no consensus about the timing, frequency, training session duration and the exact characteristics of subjects who could benefit from robotics. CONCLUSIONS: Our systematic review shows that the introduction of robotic rehabilitation in standard treatment protocols seems to be the future of stroke rehabilitation. However, robot assisted gait training (RAGT) for stroke needs to be improved with new solutions and in clinical practice guidelines, especially in terms of applicability.

How Does Stroke Affect Skeletal Muscle? State of the Art and Rehabilitation Perspective.

Long-term disability caused by stroke is largely due to an impairment of motor function. The functional consequences after stroke are caused by central nervous system adaptations and modifications, but also by the peripheral skeletal muscle changes. The nervous and muscular systems work together and are strictly dependent in their structure and function, through afferent and efferent communication pathways with a reciprocal "modulation." Knowing how altered interaction between these two important systems can modify the intrinsic properties of muscle tissue is essential in finding the best rehabilitative therapeutic approach. Traditionally, the rehabilitation effort has been oriented toward the treatment of the central nervous system damage with a central approach, overlooking the muscle tissue. However, to ensure greater effectiveness of treatments, it should not be forgotten that muscle can also be a target in the rehabilitation process. The purpose of this review is to summarize the current knowledge about the skeletal muscle changes, directly or indirectly induced by stroke, focusing on the changes induced by the treatments most applied in stroke rehabilitation. The results of this review highlight changes in several muscular features, suggesting specific treatments based on biological knowledge; on the other hand, in standard rehabilitative practice, a realist muscle function evaluation is rarely carried out. We provide some recommendations to improve a comprehensive muscle investigation, a specific rehabilitation approach, and to draw research protocol to solve the remaining conflicting data. Even if a complete multilevel muscular evaluation requires a great effort by a multidisciplinary team to optimize motor recovery after stroke.

Psycho-social impact of social distancing and isolation due to the COVID-19 containment measures on patients with physical disabilities.

BACKGROUND: While the COVID-19 pandemic was spreading worldwide, the Italian government stated lockdown, with a drastic reorganization of healthcare systems. The psychological and social effects of the pandemic and the restrictions of freedom could have had a detrimental impact on people with physical disabilities, for whom well-being depends strongly on their social environment. AIM: Our main aim was to describe the overall impact of the pandemic on mental health, social condition and illness perception among patients with disabilities, to provide early interventions for this particularly vulnerable population. For this purpose, we performed a specific screening protocol to detect the prevalence of any psychological distress. DESIGN: Cross-sectional observational study. SETTING: Telephonic interview administered to patients and their caregivers attending the Unit of Neurorehabilitation at the University Hospital of Pisa. POPULATION: 134 patients with physical disability related to neurological disorders, who had their outpatient appointment cancelled, because of the government dispositions, were enrolled. METHODS: A specific questionnaire (COVID19-q) was designed to test patients' psycho-social state, including a section addressed to the caregiver. Moreover, a standardized psychological evaluation, using the Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM), was also performed. RESULTS: Results show a different impact in our study population compared to the general population on psychological aspect. Patients did not manifest any clinically relevant distress, as assessed with CORE-OM. However, patients with higher disability degree reported a statistically lower outcome in the social function, in the well-being domains and an increase in risk behavior. Results from COVID19-q show that most of our patients reported none or mild change in their psycho-social habits and perception of illness during lockdown. However, reduction of family cohesion and lack of healthcare support are two important aspects that people with disability had to face with during the pandemic emergency. CONCLUSIONS: People with physical disabilities surprisingly shown milder effects of the pandemic on their psychological state and good coping skills in facing social isolation, manifesting resilience resources. However, the is a need to give concrete support to healthcare and social care, especially in the management of severe disability. CLINICAL REHABILITATION IMPACT: This unexpected and reassuring result may reveal a worrying scenario regarding-the social participation and quality of life of people with disabilities: were they already in lockdown?

Brain and Muscle: How Central Nervous System Disorders Can Modify the Skeletal Muscle.

It is widely known that nervous and muscular systems work together and that they are strictly dependent in their structure and functions. Consequently, muscles undergo macro and microscopic changes with subsequent alterations after a central nervous system (CNS) disease. Despite this, only a few researchers have addressed the problem of skeletal muscle abnormalities following CNS diseases. The purpose of this review is to summarize the current knowledge on the potential mechanisms responsible for changes in skeletal muscle of patients suffering from some of the most common CSN disorders (Stroke, Multiple Sclerosis, Parkinson's disease). With this purpose, we analyzed the studies published in the last decade. The published studies show an extreme heterogeneity of the assessment modality and examined population. Furthermore, it is evident that thanks to different evaluation methodologies, it is now possible to implement knowledge on muscle morphology, for a long time limited by the requirement of muscle biopsies. This could be the first step to amplify studies aimed to analyze muscle characteristics in CNS disease and developing rehabilitation protocols to prevent and treat the muscle, often neglected in CNS disease.

Muscle function impairment in cancer patients in pre-cachexia stage.

Cancer cachexia has been reported to be directly responsible for at least 20% of cancer deaths. Management of muscle wasting in cancer-associated cachexia appears to be of pivotal importance for survival of patients. In this regard, it would be interesting to identify before its patent appearance eventual functional markers of muscle damage, to plan specific exercise protocols to counteract cachexia. The muscle function of 13 oncologic patients and 15 controls was analyzed through: i) analysis of the oxidative metabolism, indirectly evaluated trough dosage of blood lactate levels before and after a submaximal incremental exercise on a treadmill; ii) analysis of strength and, iii) endurance, in both lower and upper limbs muscles, employing an isokinetic dynamometer. Statistical analyses were carried out to compare the muscle activities between groups. Analysis of oxidative metabolism during the incremental exercise on a treadmill showed that patients performed a shorter exercise than controls. Lactate levels were significantly higher in patients both at baseline and after the task. Muscle strength analysis in patients group showed a reduction of Maximum Voluntary Contraction during the isometric contraction and, a tendency to fatigue during endurance task. Data emerging from this study highlight an impairment of muscle oxidative metabolism in subjects affected by a pre-cachexia stage of cancer. A trend of precocious fatigability and an impairment of muscle strength production were also observed. This evidence underlines the relevance of assessing muscle function in order to develop novel rehabilitative approaches able to counteract motor impairment and eventually to prevent cachexia in these patients.

A multimodal approach to capture post-stroke temporal dynamics of recovery.

OBJECTIVE: Several training programs have been developed in the past to restore motor functions after stroke. Their efficacy strongly relies on the possibility to assess individual levels of impairment and recovery rate. However, commonly used clinical scales rely mainly on subjective functional assessments and are not able to provide a complete description of patients' neuro-biomechanical status. Therefore, current clinical tests should be integrated with specific physiological measurements, i.e. kinematic, muscular, and brain activities, to obtain a deep understanding of patients' condition and of its evolution through time and rehabilitative intervention. APPROACH: We proposed a multivariate approach for motor control assessment that simultaneously measures kinematic, muscle and brain activity and combines the main physiological variables extracted from these signals using principal component analysis (PCA). We tested it in a group of six sub-acute stroke subjects evaluated extensively before and after a four-week training, using an upper-limb exoskeleton while performing a reaching task, along with brain and muscle measurements. MAIN RESULTS: After training, all subjects exhibited clinical improvements correlating with changes in kinematics, muscle synergies, and spinal maps. Movements were smoother and faster, while muscle synergies increased in numbers and became more similar to those of the healthy controls. These findings were coupled with changes in cortical oscillations depicted by EEG-topographies. When combining these physiological variables using PCA, we found that (i) patients' kinematic and spinal maps parameters improved continuously during the four assessments; (ii) muscle coordination augmented mainly during treatment, and (iii) brain oscillations recovered mostly pre-treatment as a consequence of short-term subacute changes. SIGNIFICANCE: Although these are preliminary results, the proposed approach has the potential of identifying significant biomarkers for patient stratification as well as for the design of more effective rehabilitation protocols.

Biological effects of dosing aerobic exercise and neuromuscular electrical stimulation in rats.

Aerobic exercise (AE) and non-aerobic neuromuscular electric stimulation (NMES) are common interventions used in physical therapy. We explored the dose-dependency (low, medium, high) of these interventions on biochemical factors, such as brain derived neurotrophic growth factor (BDNF), vascular endothelial growth factor-A (VEGF-A), insulin-like growth factor-1 (IGF-1) and Klotho, in the blood and brain of normal rats, as well as a treadmill-based maximum capacity test (MCT). A medium dose of AE produced the most improvement in MCT with dose-dependent changes in Klotho in the blood. A dose-dependent increase of BDNF was evident following completion of an NMES protocol, but there was no improvement in MCT performance. Gene expression in the hippocampus was increased after both AE and NMES, with IGF-1 being a signaling molecule that correlated with MCT performance in the AE conditions, but also highly correlated with VEGF-A and Klotho. Blood Klotho levels can serve as a biomarker of therapeutic dosing of AE, whereas IGF-1 is a key molecule coupled to gene expression of other molecules in the hippocampus. This approach provides a translatable paradigm to investigate the mode and mechanism of action of interventions employed in physical therapy that can improve our understanding of how these factors change under pathological conditions.

A Beautician's Dystonia: Long-Lasting Effect of Botulinum Toxin.

Treatment options for dystonia are not curative but symptomatic; the treatment of choice for focal dystonias is repeated botulinum toxin injections. Here, we present the case of a 46-year-old beautician with focal dystonia in her left hand that affected her ability to work. Pharmacological treatment with clonazepam and gabapentin failed to resolve her symptoms and was discontinued due to side effects (sleepiness, gastrointestinal disorders). Intramuscular injection of botulinum toxin (incobotulinumtoxinA, Xeomin) into the extensor digitorum communis (35 U), flexor carpi radialis (35 U), and flexor digitorum superficialis (30 U) muscles resulted in complete resolution of symptoms at clinical assessments at 1, 3, 6, and 10 months after the injections, confirmed by the results of surface electromyography 10 months after treatment. The patient was able to work again 1 month after treatment. No reinjection has been necessary at the last evaluation (12 months after treatment). In conclusion, botulinum toxin is an effective treatment for focal dystonia that can have long-lasting effects and can improve patients' ability to work and quality of life.

Haptoglobin is required to prevent oxidative stress and muscle atrophy.

BACKGROUND: Oxidative stress (OS) plays a major role on tissue function. Several catabolic or stress conditions exacerbate OS, inducing organ deterioration. Haptoglobin (Hp) is a circulating acute phase protein, produced by liver and adipose tissue, and has an important anti-oxidant function. Hp is induced in pro-oxidative conditions such as systemic inflammation or obesity. The role of systemic factors that modulate oxidative stress inside muscle cells is still poorly investigated. RESULTS: We used Hp knockout mice (Hp-/-) to determine the role of this protein and therefore, of systemic OS in maintenance of muscle mass and function. Absence of Hp caused muscle atrophy and weakness due to activation of an atrophy program. When animals were stressed by acute exercise or by high fat diet (HFD), OS, muscle atrophy and force drop were exacerbated in Hp-/-. Depending from the stress condition, autophagy-lysosome and ubiquitin-proteasome systems were differently induced. CONCLUSIONS: Hp is required to prevent OS and the activation of pathways leading to muscle atrophy and weakness in normal condition and upon metabolic challenges.

Abnormal Lactate Levels Affect Motor Performance in Myotonic Dystrophy Type 1.

Myotonic Dystrophy type 1 (DM1) is a dominantly inherited disease comprehending multiple features. Fatigue and exhaustion during exercise often represent significant factors able to negatively influence their compliance to rehabilitation programs. Mitochondrial abnormalities and a significant increase in oxidative markers, previously reported, suggest the hypothesis of a mitochondrial functional impairment. The study aims at evaluating oxidative metabolism efficiency in 18 DM1 patients and in 15 healthy subjects, through analysis of lactate levels at rest and after an incremental exercise test. The exercise protocol consisted of a submaximal incremental exercise performed on an electronically calibrated treadmill, maintained in predominantly aerobic condition. Lactate levels were assessed at rest and at 5, 10 and 30 minutes after the end of the exercise. The results showed early exercise-related fatigue in DM1 patients, as they performed a mean number of 9 steps, while controls completed the whole exercise. Moreover, while resting values of lactate were comparable between the patients and the control group (p=0.69), after the exercise protocol, dystrophic subjects reached higher values of lactate, at any recovery time (p<0,05). These observations suggest an early activation of anaerobic metabolism, thus evidencing an alteration in oxidative metabolism of such dystrophic patients. As far as intense aerobic training could be performed in DM1 patients, in order to improve maximal muscle oxidative capacity and blood lactate removal ability, then, this safe and validate method could be used to evaluate muscle oxidative metabolism and provide an efficient help on rehabilitation programs to be prescribed in such patients.

Brain plasticity and recovery in preclinical models of stroke.

Post-stroke recovery relies on neurobiological changes that modify the organization and function of the brain under pathophysiological conditions. The changes can be adaptive (i.e. restoration of function) or maladaptive (i.e. worsening of function). Preclinical models of stroke exhibit adaptive plasticity that leads to a "spontaneous recov- ery" of functions. This recovery can be modulated through external factors, such as rehabilitation, pharmacology or other adjuvant strategies. Nevertheless, current interventions only result in a limited improvement of deficits and there is also potential for maladaptation. Hence, a better understanding of the mechanisms underlying recovery is essential for the design of more efficient and targeted treatment strategies. Here, we review the main features of adaptive plasticity that are thought to underlie the spontaneous and induced recovery of function in animal models of stroke. Within this context, therapeutic interventions, used in isolation or synergistically to modulate recovery, are discussed. It is hoped that a focus on neurobiological principles and their manipulation will enhance interven- tional strategies to maximize therapeutic benefit. To ensure translation of these interventions into a clinical setting, a close interaction between basic and applied research is required.

Chronic muscle stimulation improves muscle function and reverts the abnormal surface EMG pattern in myotonic dystrophy: a pilot study.

BACKGROUND: To date, in Myotonic Dystrophy type 1 (DM1) the rehabilitative interventions have always been aimed at muscle strengthening, increasing of fatigue resistance and improving of aerobic metabolism efficiency whereas the electrical membrane fault has always been addressed pharmacologically. Neuromuscular electrical stimulation (NMES) is a useful therapeutic tool in sport medicine and in the rehabilitation of many clinical conditions characterized by motor impairment such as stroke, cerebral palsy and spinal cord injury. METHODS: Five DM1 patients and one patient with Congenital Myotonia (CM) performed a home electrical stimulation of the tibialis anterior muscle lasting 15 days with a frequency of two daily sessions of 60 minutes each. Muscle strength was assessed according to the MRC scale (Medical Research Council) and functional tests (10 Meter Walking Test, 6 Minutes Walking Test and Timed Up and Go Test) were performed. We analyzed the average rectified value of sEMG signal amplitude (ARV) to characterize the sarcolemmal excitability. RESULTS: After the treatment an increase of muscle strength in those DM1 patients with a mild strength deficit was observed. In all subjects an improvement of 10MWT was recorded. Five patients improved their performance in the 6MWT. In TUG test 4 out of 6 patients showed a slight reduction in execution time. All patients reported a subjective improvement when walking. A complete recovery of the normal increasing ARV curve was observed in 4 out of 5 DM1 patients; the CM patient didn't show modification of the ARV pattern. CONCLUSIONS: NMES determined a clear-cut improvement of both the muscular weakness and the sarcolemmal excitability alteration in our small group of DM1 patients. Therefore this rehabilitative approach, if confirmed by further extensive studies, could be considered early in the management of muscular impairment in these patients. An attractive hypothesis to explain our encouraging result could be represented by a functional inhibition of SK3 channels expressed in muscle of DM1 subjects.