Restorative Neurology and Neuroscience - Volume 33, issue 6

Authors: Lee, Jungsoo | Lee, Minji | Kim, Dae-Shik | Kim, Yun-Hee

Article Type: Research Article

Abstract: Purpose: This study investigated the changes in the network topological configuration of the ipsilesional and contralesional hemispheres after a stroke and the indicators for the prediction of motor recovery using a graph theoretical approach in networks obtained from functional magnetic resonance imaging (fMRI). Methods: A longitudinal observational experiments (2 weeks and 1, 3, and 6 months after onset) were conducted on 12 patients after a stroke. We investigated the network reorganization during recovery in the ipsilesional and contralesional hemispheres by examining changes of graph indices related to network randomization. We predicted the recovery of motor function by examining …the relationship between specific network measures and improved motor function scores. Results: The ipsilesional hemispheric network showed active reorganization during recovery after a stroke. The randomness of the network significantly increased for 3 months post-stroke. We described an indicator for the prediction of the recovery of motor function from graph indices: the characteristic path length. As the path length of the ipsilesional network was lower immediately after onset, the better recovery could be expected after 3 months. Conclusions: This approach were helpful for understanding dynamic reorganizations of both hemispheric networks after a stroke and finding the implication for recovery. Show more

Keywords: Stroke, graph theoretical analysis, functional reorganization, motor recovery

DOI: 10.3233/RNN-140467

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 6, pp. 785-793, 2015

Authors: Schiemanck, Sven | Berenpas, Frank | van Swigchem, Roos | van den Munckhof, Pepijn | de Vries, Joost | Beelen, Anita | Nollet, Frans | Geurts, Alexander C.

Article Type: Research Article

Abstract: Purpose: To investigate whether an implantable functional electrical stimulation (FES) system of the common peroneal nerve (ActiGait® ) improves relevant aspects of gait in chronic stroke patients with a drop foot typically using an ankle-foot orthosis (AFO). Methods: Ten community-dwelling patients participated, of whom eight patients could be analysed. Gait quality (kinematic, kinetic, and spatiotemporal characteristics) during a 10-meter comfortable walk test, normalised net energy expenditure during a 6-minute walk test, participation (physical activity and stroke impact) and user satisfaction were tested before implantation and at various moments after FES-system activation up to 26 weeks. Results: …Walking with FES yielded increased maximum paretic ankle plantarflexion (FES: –0.12; AFO: –4.79°, p  <  0.01), higher paretic peak ankle power (FES: 1.46; AFO: 0.98 W/kg, p  <  0.05) and better step length symmetry (FES: 14.90; AFO: 21.45% , p  <  0.05). User satisfaction was higher for FES, but was unrelated to objective gait improvements. Energy expenditure and participation did not change. Conclusion: Implantable FES improved the use of residual ankle plantarflexion motion, ankle power of the paretic leg and step length symmetry compared to using an AFO, however, not resulting in decreased energy expenditure or improved participation. User satisfaction was highest with FES, but this was not related to the observed gait improvements. Show more

Keywords: Function electrical stimulation, peroneal nerve, rehabilitation, stroke, gait

DOI: 10.3233/RNN-150501

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 6, pp. 795-807, 2015

Authors: Zhao, Shanshan | Qu, Huiling | Zhao, Yi | Xiao, Ting | Zhao, Mei | Li, Yong | Jolkkonen, Jukka | Cao, Yunpeng | Zhao, Chuansheng

Article Type: Research Article

Abstract: Purpose: Forced limb-use can enhance neurogenesis and behavioral recovery as well as increasing the level of stromal cell-derived factor-1 (SDF-1) in stroke rats. We examined whether the SDF-1/CXCR4 pathway is involved in the enhanced neurogenesis and promoted behavioral recovery induced by forced limb-use in the chronic phase of stroke. Methods: The CXCR4 antagonist, AMD3100, was used to block the SDF-1/CXCR4 pathway in the ischemic rats. Brain ischemia was induced by endothelin-1. One week after ischemia, the unimpaired forelimb of rats was immobilized for 3 weeks. The proliferation, migration, and survival of DCX-positive cells in the subventricular zone (SVZ), …and the dendritic complexity of DCX-positive cells in the dentate gyrus (DG), as well as the inflammatory response in the infarcted striatum were analyzed by immunohistochemistry. Functional recovery was assessed in beam-walking and water maze tests. Results: Forced limb-use enhanced the proliferation, migration, dendritic complexity and the survival of newborn neurons. Furthermore, forced limb-use suppressed the inflammatory response and improved both motor and cognitive functions after stroke. AMD3100 significantly abrogated the enhanced neurogenesis and behavioral recovery induced by forced limb-use without influencing the inflammatory response. Conclusions: SDF-1/CXCR4 pathway seems to be involved in the enhancement of neurogenesis and behavioral recovery induced by post-stroke forced limb-use. Show more

Keywords: Forced limb-use, neurogenesis, stroke, stromal cell-derived factor-1, functional recovery

DOI: 10.3233/RNN-150515

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 6, pp. 809-821, 2015

Authors: Jiang, Jonathan L. | Yue, Zhilian | Bauquier, Sebastien H. | Lai, Alan | Chen, Yu | McLean, Karen J. | Halliday, Amy J. | Sui, Yi | Moulton, Simon | Wallace, Gordon G. | Cook, Mark J.

Article Type: Research Article

Abstract: Purpose: Epilepsy is a prevalent neurological disorder with a high frequency of drug resistance. While significant advancements have been made in drug delivery systems to overcome anti-epileptic drug resistance, efficacies of materials in biological systems have been poorly studied. The purpose of the study was to evaluate the anti-epileptic effects of injectable poly(epsilon-caprolactone) (PCL) microspheres for controlled release of an anticonvulsant, phenytoin (PHT), in an animal model of epilepsy. Methods: PHT-PCL and Blank-PCL microspheres formulated using an oil-in-water (O/W) emulsion solvent evaporation method were evaluated for particle size, encapsulation efficiency, surface morphology and in-vitro drug release profile. …Microspheres with the most suitable morphology and release characteristics weresubsequently injected into the hippocampus of a rat tetanus toxin model of temporal lobe epilepsy. Electrocorticography (ECoG)from the cerebral cortex were recorded for all animals. The number of seizure events, severity of seizures, and seizure duration were then compared between the two treatment groups. Results: We have shown that small injections of drug-loaded microspheres are biologically tolerated and released PHT can control seizures for the expected period of time that is in accord with in-vitro release data. Conclusion: The study demonstrated the feasibility of polymer-based delivery systems incontrolling focal seizures. Show more

Keywords: Biodegradable, polymer, drug delivery, epilepsy, phenytoin, microspheres

DOI: 10.3233/RNN-150520

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 6, pp. 823-834, 2015

Authors: Fan, Yang-teng | Lin, Keh-chung | Liu, Ho-ling | Chen, Yao-liang | Wu, Ching-yi

Article Type: Research Article

Abstract: Purpose: Diffusion tensor imaging (DTI) studies indicate the structural integrity of the ipsilesional corticospinal tract (CST) and the transcallosal motor tract, which are closely linked to stroke recovery. However, the individual contribution of these 2 fibers on different levels of outcomes remains unclear. Here, we used DTI tractography to investigate whether structural changes of the ipsilesional CST and the transcallosal motor tracts associate with motor and functional recovery after stroke rehabilitation. Methods: Ten participants with post-acute stroke underwent the Fugl-Meyer Assessment (FMA), the Wolf Motor Function Test (WMFT), the Functional Independence Measure (FIM), and DTI before and after …bilateral robotic training. Results: All participants had marked improvements in motor performance, functional use of the affected arm, and independence in daily activities. Increased fractional anisotropy (FA) in the ipsilesional CST and the transcallosal motor tracts was noted from pre-treatment to the end of treatment. Participants with higher pre-to-post differences in FA values of the transcallosal motor tracts had greater gains in the WMFT and the FIM scores. A greater improvement on the FMA was coupled with increased FA changes along the ipsilesional CST. Conclusions: These findings suggest 2 different structural indicators for post-stroke recovery separately at the impairment-based and function-based levels. Show more

Keywords: Diffusion tensor imaging, corticospinal tract, transcallosal motor tracts, motor recovery, stroke, rehabilitation

DOI: 10.3233/RNN-150523

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 6, pp. 835-844, 2015

Authors: Bönstrup, Marlene | Schulz, Robert | Cheng, Bastian | Feldheim, Jan | Zimerman, Máximo | Thomalla, Götz | Hummel, Friedhelm C. | Gerloff, Christian

Article Type: Research Article

Abstract: Purpose: Recovery of hand function after stroke has been associated with transient overactivation of the cerebral sensorimotor network. One open question has been as to how much this transient overactivation is related to ‘true’ reorganisation of the network or reflecting the fact that a simple motor task is difficult to perform for a patient with a motor deficit, i.e. reflecting ‘effort’. Methods: To address this, we combined a constant-output (varying effort) and constant-effort (varying output) task in a longitudinal (T1 = 3–5 days, T2 = 6 weeks, T3 = 3 months after stroke) multimodal (functional magnetic resonance imaging (FMRI), electroencephalography (EEG)) study of 12 …(EEG)/8 (FMRI) patients (7 male, age 67 ± 9 years) showing significant recovery from a hand motor deficit. Results: The reduction of sensorimotor activation from T1 to T3 was significant (p  = 0.012). But task effort did not exhibit any significant impact on the evolution of task-related brain activation over time. This proved to be equally applicable to FMRI and EEG data. Conclusion: We conclude that initial up-regulation of brain activity after stroke is not simply a consequence of enhanced effort early after stroke but rather reflects neural processes involved in reorganisation and recovery of function. Show more

Keywords: Stroke, hand motor deficit, task effort, EEG, FMRI, longitudinal study

DOI: 10.3233/RNN-150527

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 6, pp. 845-864, 2015

Authors: McDonough, Ian M. | Haber, Sara | Bischof, Gérard N. | Park, Denise C.

Article Type: Research Article

Abstract: Purpose: Correlational and limited experimental evidence suggests that an engaged lifestyle is associated with the maintenance of cognitive vitality in old age. However, the mechanisms underlying these engagement effects are poorly understood. We hypothesized that mental effort underlies engagement effects and used fMRI to examine the impact of high-challenge activities (digital photography and quilting) compared with low-challenge activities (socializing or performing low-challenge cognitive tasks) on neural function at pretest, posttest, and one year after the engagement program. Methods: In the scanner, participants performed a semantic-classification task with two levels of difficulty to assess the modulation of brain activity …in response to task demands. Results: The High-Challenge group, but not the Low-Challenge group, showed increased modulation of brain activity in medial frontal, lateral temporal, and parietal cortex—regions associated with attention and semantic processing—some of which were maintained a year later. This increased modulation stemmed from decreases in brain activity during the easy condition for the High-Challenge group and was associated with time committed to the program, age, and cognition. Conclusions: Sustained engagement in cognitively demanding activities facilitated cognition by increasing neural efficiency. Mentally-challenging activities may be neuroprotective and an important element to maintaining a healthy brain into late adulthood. Show more

Keywords: Cognitive engagement, fMRI, intervention, learning, semantic processing

DOI: 10.3233/RNN-150533

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 6, pp. 865-882, 2015

Authors: Fujiwara, Toshiyuki | Honaga, Kaoru | Kawakami, Michiyuki | Nishimoto, Atsuko | Abe, Kaoru | Mizuno, Katsuhiro | Kodama, Mitsuhiko | Masakado, Yoshihisa | Tsuji, Tetsuya | Liu, Meigen

Article Type: Research Article

Abstract: Purpose: We hypothesized that recovery of upper extremity motor function is associated with reduction of intracortical inhibition and improved reciprocal inhibition. This study examines the relationships of functional recovery in chronic stroke with the intracortical inhibition and spinal reciprocal inhibition. Methods: Participants were 61 patients with chronic hemiparetic stroke. The participants were applied hybrid assistive neuromuscular dynamic stimulation (HANDS) therapy for 3 weeks. The Fugl-Meyer test upper extremity motor score (FM) and modified Ashworth scale (MAS) were assessed before (T0 ), immediately after (T1 ) and 3 months after (T2 ) the end of HANDS therapy. A paired …pulse TMS paradigm was applied to assess short intracortical inhibition (SICI). Reciprocal inhibition (RI) was assessed with H reflex conditioning-test paradigm. Results: FM and MAS were improved until T2 . The change of FM from T0 to T2 was positively correlated with the change in affected SICI from T0 toT1 . The change of wrist MAS from T0 to T1 was positively correlated with the change of RI. Conclusions: In chronic stroke patients with moderate or severe hemiparesis, well-recovered patients showed disinhibition of ipsilesional hemisphere and increased resiprocal inhibition of forearm. Show more

Keywords: Stroke, rehabilitation, upper extremity function, motor cortex, spinal cord, transcranial magnetic stimulation, electrical stimulation, reciprocal inhibition, intracortical inhibition, motor function

DOI: 10.3233/RNN-150547

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 6, pp. 883-894, 2015

Authors: García-Álvarez, Isabel | Fernández-Mayoralas, Alfonso | Moreno-Lillo, Sandra | Sánchez-Sierra, María | Nieto-Sampedro, Manuel | Doncel-Pérez, Ernesto

Article Type: Research Article

Abstract: Purpose: After spinal cord injury (SCI) a glial scar is generated in the area affected that forms a barrier for axon growth and myelination, preventing functional recovery. Recently, we have described a synthetic glycolipid (IG20) that inhibited proliferation of human glioma cells. We show now that IG20 inhibited the proliferation of astrocytes and microglial cells, the principal cellular components of the glial scar, and promoting axonal outgrowth and myelin production in vitro . Methods: Glial cells were inhibited with IG20 (IC50≈10 μM) and studied by RT-PCR, Western Blotting, immunoprecipitation and fluorescence microscopy. Axonal outgrowth in dorsal root ganglia …(DRG) and myelin production by oligodendrocytes were analyzed by immunocytochemistry. Adult rats were assayed in spinal cord contusion model and the recovery of treated animals (n  = 6) and controls (n  = 6) was followed. Results: The IG20 was localized in the cytosol of glial cells, forming a complex with RhoGDIα , a regulator of RhoGTPases. Treatment of astroglial cultures with IG20 increase the expression of BDNF receptor genes (TrkBT1, TrkB Full). IG20 reduced the astroglial marker GFAP, while increasing production of myelin basic protein in oligodendrocytes and promoted axonal outgrowth from DRG neurons. Local injection of IG20, near a spinal cord contusion, promoted the recovery of lesioned animals analyzed by BBB test (P  <  0.05). Conclusions: We propose that inhibition of astrocytes and microglia by IG20 could be diminished the glial scar formation, inducing the re-growth and myelination of axons, these elements constitute a new approach for SCI therapy. Show more

Keywords: Astrocyte, microglia, glial scar, myelin basic protein, dorsal root ganglia, cortical neuron, spinal cord injury

DOI: 10.3233/RNN-150572

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 6, pp. 895-910, 2015

Authors: Cunningham, David A. | Varnerin, Nicole | Machado, Andre | Bonnett, Corin | Janini, Daniel | Roelle, Sarah | Potter-Baker, Kelsey | Sankarasubramanian, Vishwanath | Wang, Xiaofeng | Yue, Guang | Plow, Ela B.

Article Type: Research Article

Abstract: Purpose: To demonstrate, in a proof-of-concept study, whether potentiating ipsilesional higher motor areas (premotor cortex and supplementary motor area) augments and accelerates recovery associated with constraint induced movement. Methods: In a randomized, double-blinded pilot clinical study, 12 patients with chronic stroke were assigned to receive anodal transcranial direct current stimulation (tDCS) (n  = 6) or sham (n  = 6) to the ipsilesional higher motor areas during constraint-induced movement therapy. We assessed functional and neurophysiologic outcomes before and after 5 weeks of therapy. Results: Only patients receiving tDCS demonstrated gains in function and dexterity. Gains were accompanied by an …increase in excitability of the contralesional rather than the ipsilesional hemisphere. Conclusions: Our proof-of-concept study provides early evidence that stimulating higher motor areas can help recruit the contralesional hemisphere in an adaptive role in cases of greater ipsilesional injury. Whether this early evidence of promise translates to remarkable gains in functional recovery compared to existing approaches of stimulation remains to be confirmed in large-scale clinical studies that can reasonably dissociate stimulation of higher motor areas from that of the traditional primary motor cortices. Show more

Keywords: Stroke rehabilitation, transcranial direct current stimulation, constraint-induced movement therapy, premotor cortex, motor recovery, transcranial magnetic stimulation

DOI: 10.3233/RNN-150574

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 6, pp. 911-926, 2015