Neurorehabilitation and Neural Repair

Background: In the chronic phase after stroke, cortical excitability differs between the cerebral hemispheres; the magnitude of this asymmetry depends on degree of motor impairment. It is unclear whether these asymmetries also affect capacity for plasticity in corticospinal tract excitability or whether hemispheric differences in plasticity are related to chronic sensorimotor impairment. Methods: Response to paired associative stimulation (PAS) was assessed bilaterally in 22 individuals with chronic hemiparesis. Corticospinal excitability was measured as the area under the motor-evoked potential (MEP) recruitment curve (AUC) at baseline, 5 minutes, and 30 minutes post-PAS. Percentage change in contralesional AUC was calculated and correlated with paretic motor and somatosensory impairment scores. Results: PAS induced a significant increase in AUC in the contralesional hemisphere (P = .041); in the ipsilesional hemisphere, there was no significant effect of PAS (P = .073). Contralesional AUC showed significantly greater change in individuals without an ipsilesional MEP (P = .029). Percentage change in contralesional AUC between baseline and 5 m post-PAS correlated significantly with FM score (r = −0.443; P = .039) and monofilament thresholds (r = 0.444, P = .044). Discussion: There are differential responses to PAS within each cerebral hemisphere. Contralesional plasticity was increased in individuals with more severe hemiparesis, indicated by both the absence of an ipsilesional MEP and a greater degree of motor and somatosensory impairment. These data support a body of research showing compensatory changes in the contralesional hemisphere after stroke; new therapies for individuals with chronic stroke could exploit contralesional plasticity to help restore function.

Background. The added prognostic value of transcranial magnetic stimulation (TMS)-induced motor-evoked potentials (MEPs) to clinical modeling for the upper limb is still unknown early poststroke. Objective. To determine the added prognostic value of TMS of the adductor digiti minimi (TMS-ADM) to the clinical model based on voluntary shoulder abduction (SA) and finger extension (FE) during the first 48 hours and at 11 days after stroke. Methods. This was a prospective cohort study with 3 logistic regression models, developed to predict upper-limb function at 6 months poststroke. The first model showed the predictive value of SA and FE measured within 48 hours and at 11 days poststroke. The second model included TMS-ADM, whereas the third model combined clinical and TMS-ADM information. Differences between derived models were tested with receiver operating characteristic curve analyses. Results. A total of 51 patients with severe, first-ever ischemic stroke were included. Within 48 hours, no significant added value of TMS-ADM to clinical modeling was found (P = .369). Both models suffered from a relatively low negative predictive value within 48 hours poststroke. TMS-ADM combined with SA and FE (SAFE) showed significantly more accuracy than TMS-ADM alone at 11 days poststroke (P = .039). Conclusion. TMS-ADM showed no added value to clinical modeling when measured within first 48 hours poststroke, whereas optimal prediction is achieved by SAFE combined with TMS-ADM at 11 days poststroke. Our findings suggest that accuracy of predicting upper-limb motor function by TMS-ADM is mainly determined by the time of assessment early after stroke onset.

Background. Proportional motor recovery in the upper limb has been investigated, indicating about 70% of the potential for recovery of motor impairment within the first months poststroke. Objective. To investigate whether the proportional recovery rule is applicable for upper-limb somatosensory impairment and to study underlying neural correlates of impairment and outcome at 6 months. Methods. A total of 32 patients were evaluated at 4 to 7 days and 6 months using the Erasmus MC modification of the revised Nottingham Sensory Assessment (NSA) for impairment of (1) somatosensory perception (exteroception) and (2) passive somatosensory processing (sharp/blunt discrimination and proprioception); (3) active somatosensory processing was evaluated using the stereognosis component of the NSA. Magnetic resonance imaging scans were obtained within 1 week poststroke, from which lesion load (LL) was calculated for key somatosensory tracts. Results. Somatosensory perception fully recovered within 6 months. Passive and active somatosensory processing showed proportional recovery of 86% (95% CI = 79%-93%) and 69% (95% CI = 49%-89%), respectively. Patients with somatosensory impairment at 4 to 7 days showed significantly greater thalamocortical and insulo-opercular tracts (TCT and IOT) LL (P < .05) in comparison to patients without impairment. Sensorimotor tract disruption at 4 to 7 days did not provide significant contribution above somatosensory processing score at 4 to 7 days when predicting somatosensory processing outcome at 6 months. Conclusions. Our sample of stroke patients assessed early showed full somatosensory perception but proportional passive and active somatosensory processing recovery. Disruption of both the TCT and IOT early after stroke appears to be a factor associated with somatosensory impairment but not outcome.

Changes in the control of the lower extremities poststroke lead to persistent biomechanical asymmetries during walking. These asymmetries are associated with an increase in energetic cost, leading to the possibility that reducing asymmetry can improve walking economy. However, the influence of asymmetry on economy may depend on the direction and cause of asymmetry. For example, impairments with paretic limb advancement may result in shorter paretic steps, whereas deficits in paretic support or propulsion result in shorter nonparetic steps. Given differences in the underlying impairments responsible for step length asymmetry, the capacity to reduce asymmetry and the associated changes in energetic cost may not be consistent across this population. Here, we identified factors explaining individual differences in the capacity to voluntarily reduce step length asymmetry and modify energetic cost during walking. A total of 24 individuals poststroke walked on a treadmill, with visual feedback of their step lengths to aid explicit modification of asymmetry. We found that individuals who took longer paretic steps had a greater capacity to reduce asymmetry and were better able to transfer the effects of practice to overground walking than individuals who took shorter paretic steps. In addition, changes in metabolic cost depended on the direction of asymmetry, baseline cost of transport, and reductions in specific features of spatiotemporal asymmetry. These results demonstrate that many stroke survivors retain the residual capacity to voluntarily walk more symmetrically on a treadmill and overground. However, whether reductions in asymmetry reduce metabolic cost depends on individual differences in impairments affecting locomotor function.

Background. Contradictory results have been reported for transcranial direct current stimulation (tDCS) as treatment for tinnitus. The recently developed high-definition tDCS (HD tDCS) uses smaller electrodes to limit the excitation to the desired brain areas. Objective. The current study consisted of a retrospective part and a prospective part, aiming to compare 2 tDCS electrode placements and to explore effects of HD tDCS by matched pairs analyses. Methods. Two groups of 39 patients received tDCS of the dorsolateral prefrontal cortex (DLPFC) or tDCS of the right supraorbital–left temporal area (RSO-LTA). Therapeutic effects were assessed with the tinnitus functional index (TFI), a visual analogue scale (VAS) for tinnitus loudness, and the hyperacusis questionnaire (HQ) filled out at 3 visits: pretherapy, posttherapy, and follow-up. With a new group of patients and in a similar way, the effects of HD tDCS of the right DLPFC were assessed, with the tinnitus questionnaire (TQ) and the hospital anxiety and depression scale (HADS) added. Results. TFI total scores improved significantly after both tDCS and HD tDCS (DLPFC: P < .01; RSO-LTA: P < .01; HD tDCS: P = .05). In 32% of the patients, we observed a clinically significant improvement in TFI. The 2 tDCS groups and the HD tDCS group showed no differences on the evolution of outcomes over time (TFI: P = .16; HQ: P = .85; VAS: P = .20). Conclusions. TDCS and HD tDCS resulted in a clinically significant improvement in TFI in 32% of the patients, with the 3 stimulation positions having similar results. Future research should focus on long-term effects of electrical stimulation.

Background. Humans use voluntary eye movements to actively gather visual information during many activities of daily living, such as driving, walking, and preparing meals. Most stroke survivors have difficulties performing these functional motor tasks, and we recently demonstrated that stroke survivors who require many saccades (rapid eye movements) to plan reaching movements exhibit poor motor performance. However, the nature of this relationship remains unclear. Objective. Here we investigate if saccades interfere with speed and smoothness of reaching movements in stroke survivors, and if excessive saccades are associated with difficulties performing functional tasks. Methods. We used a robotic device and eye tracking to examine reaching and saccades in stroke survivors and age-matched controls who performed the Trail Making Test, a visuomotor task that uses organized patterns of saccades to plan reaching movements. We also used the Stroke Impact Scale to examine difficulties performing functional tasks. Results. Compared with controls, stroke survivors made many saccades during ongoing reaching movements, and most of these saccades closely preceded transient decreases in reaching speed. We also found that the number of saccades that stroke survivors made during ongoing reaching movements was strongly associated with slower reaching speed, decreased reaching smoothness, and greater difficulty performing functional tasks. Conclusions. Our findings indicate that poststroke interference between eye and limb movements may contribute to difficulties performing functional tasks. This suggests that interventions aimed at treating impaired organization of eye movements may improve functional recovery after stroke.

Background. Peripheral axon regeneration is improved when the nerve lesion under consideration has recently been preceded by another nerve injury. This is known as the conditioning lesion effect (CLE). While the CLE is one of the most robust and well characterized means to enhance motor axon regeneration in experimental models, it is not considered a clinically feasible strategy. A pharmacological means to re-produce the CLE is highly desirable. Objective. To test whether chemodenervation with a clinical grade formulation of botulinum toxin A (BoTX) would be sufficient to reproduce the CLE. Methods. We examined the effects of a 1-week preconditioning administration of BoTX on motor axon regrowth in both a mouse tibial nerve injury and human embryonic stem cell (hESC)–based model. We assessed neuronal reinnervation in vivo (mice) with retrograde tracers and histological analysis of peripheral nerve tissue after injections into the triceps surae muscle group. We assessed motor neuron neurite outgrowth in vitro (hESC) after incubation in BoTX by immunohistochemistry and morphometric analysis. Results. We found that BoTX conditioning treatment significantly enhanced outgrowth of both murine motor axons in vivo and human MN neurites in vitro. Conclusions. BoTX preconditioning represents a pharmacological candidate approach to enhance motor axon regeneration in specific clinical scenarios such as nerve transfer surgery. Further studies are needed to elucidate the molecular mechanism.