Neuromuscular Stimulation as an Intervention Tool for Recovery from Upper Limb Paresis after Stroke and the Neural Basis

Neuromodulators at the periphery, such as neuromuscular electrical stimulation (NMES), have been developed as add-on tools to regain upper extremity (UE) paresis after stroke, but this recovery has often been limited. To overcome these limits, novel strategies to enhance neural reorganization and functional recovery are needed. This review aims to discuss possible strategies for enhancing the benefits of NMES. To date, NMES studies have involved some therapeutic concerns that have been addressed under various conditions, such as the time of post-stroke and stroke severity and/or with heterogeneous stimulation parameters, such as target muscles, doses or durations of treatment and outcome measures. We began by identifying factors sensitive to NMES benefits among heterogeneous conditions and parameters, based on the “progress rate (PR)”, defined as the gains in UE function scores per intervention duration. Our analysis disclosed that the benefits might be affected by the target muscles, stroke severity and time period after stroke. Likewise, repetitive peripheral neuromuscular magnetic stimulation (rPMS) is expected to facilitate motor recovery, as already demonstrated by a successful study. In parallel, our efforts should be devoted to further understanding the precise neural mechanism of how neuromodulators make UE function recovery occur, thereby leading to overcoming the limits. In this study, we discuss the possible neural mechanisms.

Post-stroke Rehabilitation of Severe Upper Limb Paresis in Germany – Toward Long-Term Treatment With Brain-Computer Interfaces

Severe upper limb paresis can represent an immense burden for stroke survivors. Given the rising prevalence of stroke, restoration of severe upper limb motor impairment remains a major challenge for rehabilitation medicine because effective treatment strategies are lacking. Commonly applied interventions in Germany, such as mirror therapy and impairment-oriented training, are limited in efficacy, demanding for new strategies to be found. By translating brain signals into control commands of external devices, brain-computer interfaces (BCIs) and brain-machine interfaces (BMIs) represent promising, neurotechnology-based alternatives for stroke patients with highly restricted arm and hand function. In this mini-review, we outline perspectives on how BCI-based therapy can be integrated into the different stages of neurorehabilitation in Germany to meet a long-term treatment approach: We found that it is most appropriate to start therapy with BCI-based neurofeedback immediately after early rehabilitation. BCI-driven functional electrical stimulation (FES) and BMI robotic therapy are well suited for subsequent post hospital curative treatment in the subacute stage. BCI-based hand exoskeleton training can be continued within outpatient occupational therapy to further improve hand function and address motivational issues in chronic stroke patients. Once the rehabilitation potential is exhausted, BCI technology can be used to drive assistive devices to compensate for impaired function. However, there are several challenges yet to overcome before such long-term treatment strategies can be implemented within broad clinical application: 1. developing reliable BCI systems with better usability; 2. conducting more research to improve BCI training paradigms and 3. establishing reliable methods to identify suitable patients.

Relationships between accelerometry and general compensatory movements of the upper limb after stroke

Background Standardized assessments are used in rehabilitation clinics after stroke to measure restoration versus compensatory movements of the upper limb. Accelerometry is an emerging tool that can bridge the gap between in- and out-of-clinic assessments of the upper limb, but is limited in that it currently does not capture the quality of a person’s movement, an important concept to assess compensation versus restoration. The purpose of this analysis was to characterize how accelerometer variables may reflect upper limb compensatory movement patterns after stroke. Methods This study was a secondary analysis of an existing data set from a Phase II, single-blind, randomized, parallel dose–response trial (NCT0114369). Sources of data utilized were: (1) a compensatory movement score derived from video analysis of the Action Research Arm Test (ARAT), and (2) calculated accelerometer variables quantifying time, magnitude and variability of upper limb movement from the same time point during study participation for both in-clinic and out-of-clinic recording periods. Results Participants had chronic upper limb paresis of mild to moderate severity. Compensatory movement scores varied across the sample, with a mean of 73.7 ± 33.6 and range from 11.5 to 188. Moderate correlations were observed between the compensatory movement score and each accelerometer variable. Accelerometer variables measured out-of-clinic had stronger relationships with compensatory movements, compared with accelerometer variables in-clinic. Variables quantifying time, magnitude, and variability of upper limb movement out-of-clinic had relationships to the compensatory movement score. Conclusions Accelerometry is a tool that, while measuring movement quantity, can also reflect the use of general compensatory movement patterns of the upper limb in persons with chronic stroke. Individuals who move their limbs more in daily life with respect to time and variability tend to move with less movement compensations and more typical movement patterns. Likewise, individuals who move their paretic limbs less and their non-paretic limb more in daily life tend to move with more movement compensations at all joints in the paretic limb and less typical movement patterns.

Imaging biomarkers for primary motor outcome after stroke – should we include information from beyond the primary motor system?

Hemiparesis is a common consequence of stroke to the primary motor system. Previous studies suggested that damage to additional brain areas might play a causal role in occurrence and severity of hemiparesis and its recovery. Imaging biomarkers to predict post stroke outcome thus might also account for damage to these non-primary motor areas. The study aimed to evaluate if damage to areas outside of the primary motor system is predictive of hemiparesis, and if this damage plays a causal role in its occurrence. In 102 patients with unilateral stroke, the neural correlates of acute and chronic upper limb paresis were mapped by univariate and multivariate lesion behaviour mapping. Following the same approach, CST lesion biomarkers were mapped, and resulting topographies of both analyses were compared. All mapping analyses of acute or chronic upper limb paresis implicated areas outside of the primary motor system. Likewise, mapping CST lesion biomarkers ‒ that, by definition, are only causally related to damage of the CST ‒ implicated several areas outside of the CST with high correspondence to areas associated with upper limb paresis. Damage to areas outside of the primary motor system might not play a causal role in hemiparesis, while still providing predictive value. This finding suggests that simple theory-based biomarkers or qualitative rules to infer post-stroke outcome from imaging data might perform sub-optimally, as they do not consider the complexity of lesion data. Instead, high-dimensional models with data-driven feature selection strategies might be required.

Nelarabine-associated myelopathy in a patient with acute lymphoblastic leukaemia: Case report

Introduction Nelarabine is a purine analogue approved for the treatment of patients with T-cell lymphoblastic lymphoma and T-cell acute lymphoblastic leukaemia (T-ALL) that have relapsed or are refractory to two previous chemotherapy regimens. Adverse reactions to nelarabine include neurological toxicity, the pathophysiological mechanisms of which are unknown, although the administration of intrathecal therapy at therapeutic doses given concomitantly with high-dose systemic chemotherapy that crosses the blood–brain barrier may potentiate neurotoxicity. Case report We report a case of a 29-year-old woman with a diagnosis of relapsed T-ALL who developed severe myelopathy and polyneuropathy of toxic origin that led to paraplegia, upper-limb paresis, and dysautonomia after the first cycle of nelarabine. Management and outcome Rehabilitation and pharmacological treatments were initiated early, but no evidence of a significant clinical change was obtained. Discussion Neurotoxicity is a dose-dependent side effect of nelarabine. It is therefore important to consider previously administered neurotoxic drugs before using nelarabine and to monitor patients closely so as to be able to act promptly in case of toxicity. In accordance with the data obtained and based on the Naranjo algorithm, the adverse reaction could be considered possible.