Restorative Neurology and Neuroscience - Volume 37, issue 5

Authors: Morkisch, Nadine | Thieme, Holm | Dohle, Christian

Article Type: Research Article

Abstract: Background: A recently updated Cochrane review for mirror therapy (MT) showed a high level of evidence in the treatment of hemiparesis after stroke. However, the therapeutic protocols used in the individual studies showed significant variability. Objective: A secondary meta-analysis was performed to detect which parameters of these protocols may influence the effect of MT for upper limb paresis after stroke. Methods: Trials included in the Cochrane review, which published data for motor function / impairment of the upper limb, were subjected to this analysis. Trials or trial arms that used MT as group therapy or combined …it with electrical or magnetic stimulation were excluded. The analysis focused on the parameters mirror size, uni- or bilateral movement execution, and type of exercise. Data were pooled by calculating the total weighted standardized mean difference and the 95% confidence interval. Results: Overall, 32 trials were included. The use of a large mirror compared to a small mirror showed a higher effect on motor function. Movements executed unilaterally showed a higher effect on motor function than a bilateral execution. MT exercises including manipulation of objects showed a minor effect on motor function compared to movements excluding the manipulation of objects. None of the subgroup differences reached statistical significance. Conclusions: The results of this analysis suggest that the effects on both motor function and impairment of the affected upper limb depend on the therapy protocol. They furthermore indicate that a large mirror, unilateral movement execution and exercises without objects may be parameters that enhance the effects of MT for improving motor function after stroke. Show more

Keywords: Stroke, paresis, rehabilitation, mirror therapy, meta-analysis

DOI: 10.3233/RNN-190935

Citation: Restorative Neurology and Neuroscience, vol. 37, no. 5, pp. 421-435, 2019

Authors: Ramachandran, Vilayanur Subramanian | Rogers-Ramachandran, Diane

Article Type: Editorial

Abstract: 1 out of 6 people worldwide will have suffered a stroke in their lifetime, 1/3rd of whom will die. Of the 2/3rd who survive, half will be permanently disabled (World Stroke Organization). Given these alarming statistics, it’s not surprising that tremendous of amounts of time, resources and funding have been devoted towards research into stroke rehab. In view of this, simple, easy-to-implement procedures are highly sought after. One such procedure is the use of visual feedback conveyed by a mirror, which seems to reactivate some dormant pathways in patients who have suffered a recent stroke (Altschuler et al., 1999 ; Ramachandran …& Altschuler, 2009 ). This procedure has been validated in several dozen clinical trials, of which a substantial number were conducted rigorously. Morkisch et al. (2019) now present a systematic review and meta-analysis of this dense literature pertaining to this topic. They conclude that “there is a high level evidence for mirror therapy’s effectiveness in treating post-stroke hemiparesis”. A novel conclusion that emerged from this meta-analysis was that the larger the mirror the more effective the treatment is. Additionally, if an object is manipulated by the normal hand and its reflection viewed in the mirror, the procedure is not as effective, possibly because the discrepancy of signals between the visual feedback (reflection of the object) and the lack of confirmatory somatosensory input from the affected limb leads to inhibition rather than synergy. Lastly, for reasons yet unclear, sending movement commands to the unaffected hand alone (unilateral) is more effective than sending bilateral commands, contrary to the original protocol. Taken collectively, research in this field has two implications – First, the immediate practical utility in the clinic by optimizing mirror therapy’s efficacy for hemiparesis after stroke. Second, it leads to a rejection of the model of the brain as made up of isolated, autonomous modules, towards a more dynamic picture, in which the brain is composed of a fluctuating mosaic of neural activity as it adapts to changing sensory inputs. Therefore, dysfunction results not from ‘punch out a module – lose a function’, but by shifts in equilibria, which can be corrected, perhaps, by hitting a reset button. Even if this turns out to be true for a minority of syndromes, it will be well worth the effort. Show more

DOI: 10.3233/RNN-190971

Citation: Restorative Neurology and Neuroscience, vol. 37, no. 5, pp. 437-443, 2019

Authors: Bakker, C.D. | Massa, M. | Daffertshofer, A. | Pasman, J.W. | van Kuijk, A.A. | Kwakkel, G. | Stegeman, D.F.

Article Type: Research Article

Abstract: Background: Within the first 72 hours after stroke, active finger extension is a strong predictor of long-term dexterity. Transcranial magnetic stimulation may add prognostic value to clinical assessment, which is especially relevant for patients unable to follow instructions. Objective: The current prospective cohort study aims at determining whether amplitude of motor evoked potentials of the extensor digitorum communis (EDC) can improve clinical prediction after stroke when added to clinical tests. Methods: the amplitude of motor evoked potentials of the affected EDC muscle at rest was measured in 18 participants within 4 weeks after stroke, as were …the ability to perform finger extension and the Fugl-Meyer Motor Assessment of the upper extremity (FMA_UE). These three determinants were related to the FMA_UE at 26 weeks after stroke (FMA_UE26), both directly, and via the proportional recovery prediction model. The relation between amplitude of the motor evoked potentials and FMA_UE26 was evaluated for EDC. For comparison, also the MEP amplitudes of biceps brachii and adductor digiti minimi muscles were recorded. Results: Patients’ ability to voluntarily extend the fingers was strongly related to FMA_UE26, in our cohort there were no false negative results for this predictor. Our data revealed that the relation between amplitude of motor evoked potential of EDC and FMA_UE26 was significant, but moderate (rs  = 0.58) without added clinical value. The other tested muscles did not correlate significantly to FMA_UE26. Conclusions: Our study demonstrates no additional value of motor evoked potential amplitude of the affected EDC muscle to the clinical test of finger extension, the latter being more strongly related to FMA_UE26. Show more

Keywords: Transcranial magnetic stimulation (TMS), upper extremity, prognosis

DOI: 10.3233/RNN-180890

Citation: Restorative Neurology and Neuroscience, vol. 37, no. 5, pp. 445-456, 2019

Authors: Gaston, Tyler E. | Nair, Sangeeta | Allendorfer, Jane B. | Martin, Roy C. | Beattie, Julia Fleming | Szaflarski, Jerzy P.

Article Type: Research Article

Abstract: Background: Memory deficits are very common in epilepsy, but no standard of care exists to effectively manage them. Objective: We assessed effectiveness of cognitive rehabilitation (CR) on memory and neural plasticity in people with epilepsy (PWE) reporting memory impairments. Methods: Nine PWE completed 6 weekly sessions adapted from 2 generic CR programs enriched with information regarding epilepsy. Participants completed neuropsychological, mood, and quality of life (QOLIE-31) measures prior and after completion of CR; 5/9 participants also completed pre- and post-CR fMRI while performing a verbal paired associates learning task. FMRI data were analyzed using …group spatial independent components analysis methods; paired t -tests compared spatial activations for pre-/post-CR. Results: Improvements were seen in immediate recall in Rey Auditory Verbal Learning Task, QOLIE-31, and read word recognition in paired associates task (all p’s≤0.05). FMRI changes comparing pre-to-post CR were noted through increased activation in the left inferior frontal gyrus (IFG) and anterior cingulate and decreased activation in the left superior temporal gyrus; also noted were decreased activations in the default mode network (DMN), right cingulate, right middle temporal gyrus, right supramarginal gyrus, and increased DMN activation in the left cuneus. Conclusions: This study demonstrates feasibility of conducting CR program in PWE with fMRI as a mechanistic biomarker. Improvements in cognition and cortical plasticity await confirmation in larger samples. Show more

Keywords: Memory, epilepsy, memory impairment, rehabilitation, intervention, fMRI, paired associate learning task

DOI: 10.3233/RNN-190919

Citation: Restorative Neurology and Neuroscience, vol. 37, no. 5, pp. 457-468, 2019

Authors: Dusane, Shamali | Wang, Edward | Bhatt, Tanvi

Article Type: Research Article

Abstract: Background: Chronic stroke survivors demonstrate the potential to acquire reactive adaptations to external perturbations. However, such adaptations in postural stability and compensatory stepping responses are perturbation-type specific and the ability to generalize such adaptation to an opposing perturbation has not been studied. Objective: The study aimed to examine whether improved reactive balance control acquired through prior slip-perturbation training would positively transfer to, or interfere with, the reactive response to an unexpected novel trip. Methods: Twenty-six chronic stroke survivors were assigned to either the training group (TR) who received treadmill-induced slips (12 m/s2 ) while standing followed by …a novel trip (16.8 m/s2 ) or the control group (TC) who experienced a single unannounced trip. The primary outcome measure was postural stability (examined by relative center of mass position (RCoMP) and velocity (RCoMV)) with step length and trunk angle being secondary measures. Perturbation outcome (fall vs recovery) and number of compensatory steps were also recorded. Results: The TR group showed an anterior shift in RCoMP via longer compensatory backward step and reduced number of steps from first to last slip-perturbation (p  < 0.05). Post-slip adaptation, the TR group exhibited a more posterior RCoMP on the novel trip along with a longer forward step and decreased trunk flexion compared to the TC group (p  < 0.05). Conclusions: Chronic stroke survivors demonstrated improved direction-specific compensatory stepping response on a novel trip-perturbation following reactive adaptation to large-magnitude, stance-slip perturbation training. The present study investigates the ability of chronic stroke survivors to generalize motor adaptation from stance-slip perturbation training to a novel, diametrically opposing trip-perturbation. We report that people with chronic hemi-paretic stroke could execute the acquired adaptation in reactive postural stability to improve reactive stepping responses to a novel stance-trip perturbation via generation of a direction-specific effective compensatory stepping response, such that the training group demonstrated a longer forward compensatory step and better control of postural stability than the control group. Show more

Keywords: Perturbation training, adaptation, generalization, stroke

DOI: 10.3233/RNN-190924

Citation: Restorative Neurology and Neuroscience, vol. 37, no. 5, pp. 469-482, 2019

Authors: Zhang, Jack Jiaqi | Fong, Kenneth N.K.

Article Type: Research Article

Abstract: Background: Excitatory brain stimulation, in the form of intermittent theta burst stimulation (iTBS), combined with mirror visual feedback (MVF), is hypothesized to promote neuroplasticity and motor performance. Objective: This study aimed to investigate the combined effects of iTBS with mirror training (MT) on the MVF-induced sensorimotor event-related desynchronization (ERD) and the non-dominant hand motor performance in healthy adults. Methods: Eighteen healthy right-handed subjects were randomly assigned to one of three groups (Group 1: iTBS plus MT, Group 2: iTBS plus sham MT, or Group 3: sham iTBS plus MT). For participants in Groups 1 and 3, …motor training was performed for 15 minutes for the right hand over four consecutive days, with MVF superimposing on their inactive left hand behind a mirror. Participants in Group 2 received the same right-hand motor training, but the mirror was covered without MVF. iTBS or sham iTBS was applied daily over the right primary motor cortex prior to the training. Electroencephalography at pre/post-training was recorded while participants performed right-hand movement under mirror and direct view. Motor performance was assessed at baseline and post-training. Results: Baseline comparisons demonstrated that a shift in sensorimotor ERD towards the right hemisphere was induced by MVF, in mu-1 (8–10 Hz) (p  = 0.002), mu-2 (10–12 Hz) (p  = 0.004) and beta-1 (12–16 Hz) (p  = 0.049) bands. After the training, participants in Group 1 showed a stronger MVF-induced sensorimotor ERD in mu-1 (p  = 0.017) and mu-2 (p  = 0.009) bands than those in Group 3. No significant between-group difference in motor outcomes was observed. Conclusions: iTBS appears to prime subjects’ brain to be more receptive to MVF. Show more

Keywords: Theta burst stimulation, mirror visual feedback, event-related desynchronization, mirror neuron system

DOI: 10.3233/RNN-190927

Citation: Restorative Neurology and Neuroscience, vol. 37, no. 5, pp. 483-495, 2019

Authors: Sun, Xiaolong | Long, Hua | Zhao, Chenguang | Duan, Qiang | Zhu, Huilin | Chen, Chunyan | Sun, Wei | Ju, Fen | Sun, Xinyan | Zhao, Yilin | Xue, Baijie | Tian, Fei | Mou, Xiang | Yuan, Hua

Article Type: Research Article

Abstract: Background: Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment for chronic intractable neuropathic pain in patients with spinal cord injury (SCI). However, the analgesia-enhancing effects of rTMS on conventional interventions (e.g., medications), and the underlying mechanisms remain poorly understood. Objective: To investigate the enhancement of analgesia and change of cortex activation by rTMS treatment on neuropathic pain following SCI. Methods: A double-blind, sham-controlled, clinical trial was performed. Twenty-one patients with neuropathic pain after SCI were randomized (2:1) to receive a session of rTMS (10 Hz, a total of 1200 pulses at an intensity of 80% resting …motor threshold) or sham treatment over the left primary motor cortex (M1) corresponding to the hand area daily for six weeks with a one-day interval per week. At T0 (before rTMS treatment), T1 (after the first session rTMS), T2 (after one week), T3 (after two weeks), T4 (after four weeks) and T5 (after six weeks), activations in the bilateral M1, primary somatosensory cortex (S1), premotor cortex (PMC) and prefrontal cortex (PFC) during the handgrip task were measured using functional near-infrared spectroscopy (fNIRS). In addition, the numerical rating scale (NRS) was used to assess pain. Results: The pain intensity or activation in PFC, PMC, M1 or S1 was not remarkably changed at T1. Along with the time, the pain intensity gradually decreased in both the rTMS and sham groups. The real rTMS, compared with the sham, showed more pain relief from two weeks (T3) to six weeks (T5), and the activations of the motor-related areas M1 and PMC were remarkably suppressed. Conclusions: The findings of this preliminary study with a small patient sample suggest that the analgesia-enhancing effects of high-frequency rTMS might be related with the amelioration of M1 and PMC hypersensitivity, shedding light upon the clinical treatment of SCI-related neuropathic pain. Show more

Keywords: rTMS, neuropathic pain, spinal cord injury, fNIRS

DOI: 10.3233/RNN-190934

Citation: Restorative Neurology and Neuroscience, vol. 37, no. 5, pp. 497-507, 2019

Authors: Lodha, Neha | Patel, Prakruti | Harrell, Jane | Casamento-Moran, Agostina | Zablocki, Victoria | Christou, Evangelos A. | Poisson, Sharon N.

Article Type: Research Article

Abstract: Background: Unilateral motor impairment is a key symptom used in the diagnosis of transient ischemic attack (TIA). Diffusion-weighted imaging (DWI) is a promising diagnostic tool for detecting ischemic lesions. While both motor impairments and DWI abnormalities are linked to the diagnosis of TIA, the association between these prognostic factors is not well understood. Objective: To examine the association between unilateral motor impairments and the odds of a positive DWI in TIA. Further, to determine whether the time between symptom onset and neuroimaging (delay to scan) influences the odds of a positive DWI. Methods: We used PRISMA …guidelines to conduct a systematic search from 1989 to 2018. We included studies that reported number of individuals with/without unilateral motor symptoms and a positive/negative DWI. Results: Twenty-four studies from North America, Australia, Asia, and Europe were submitted to a meta-analysis. A pooled odds ratio of 1.80 (95% CI, 1.45–2.24, p  = 0.00; I2  = 57.38) suggested that the odds of a positive DWI are greater in TIA individuals who experience motor symptoms as compared with those who experience no motor symptoms. Further, increasing the time delay to scan from the symptom onset (>2 days) did not influence the odds of a positive DWI as compared with an earlier scan (≤2 days). Conclusions: The current meta-analysis provides cumulative evidence from 6710 individuals with TIA that the presence of motor symptoms increases the odds of a positive DWI by two-folds. These findings transform the clinical perception into evidence-based knowledge that motor impairments elevate the risk for brain tissue damage. Unilateral motor impairments in a cerebrovascular event should increase a physician’s suspicion of detecting brain infarctions. These findings may influence the clinical management of TIA by generating faster response to motor impairments in TIA and accelerating referral to specialized stroke clinic. Show more

Keywords: TIA, minor stroke, sensorimotor deficits, brain imaging, risk

DOI: 10.3233/RNN-190940

Citation: Restorative Neurology and Neuroscience, vol. 37, no. 5, pp. 509-521, 2019