Restorative Neurology and Neuroscience - Volume 38, issue 1

Authors: Xu, Zi-Xing | Albayar, Ahmed | Dollé, Jean-Pierre | Hansel, Gisele | Bianchini, Justin | Sullivan, Patricia Zadnik | Cullen, D. Kacy | Smith, Douglas H. | Ozturk, Ali K.

Article Type: Research Article

Abstract: Background: Spinal cord injury (SCI) patients represent a heterogeneous group, with injuries ranging from partial compression to complete transection. Patients with complete injuries are unlikely to exhibit recovery and suffer from paralysis as well as the loss of bowel and bladder function. One treatment option is the formation of a bridge through a lesion site, whereby transplanted cells or biocompatible scaffolds guide the regenerating axons across the site of injury. Moreover, the viability of transplanted dorsal root ganglia (DRGs) into rat spinal cord has been previously demonstrated. Objective: We aim to demonstrate the feasibility of using DRG axons …as a bridging tool to help guide the axonal growth of cortical neurons. Methods: Cortical neurons were isolated from embryonic rats and two aggregated populations were cultured at increasing distances in isolation and in a co-culture with DRG explants. Growth rates of the sprouting axons and connections between the two populations were observed over a period of twelve days. Results: DRG explants demonstrated the ability to grow robust axonal connections that can connect two explants separated by up to 10 mm, however, CNAs could not achieve connections in distances greater than 2 mm. The co-culture of CNAs with DRG explants facilitated axonal growth between two populations of CNAs at distances they cannot otherwise traverse. Conclusions: Our findings support the use of DRG axons to facilitate the growth of cortical neurons in a process of axon-facilitated axon regeneration. We believe these results could have implications for the treatment of SCI. Show more

Keywords: Traumatic brain injury (TBI), central nervous system regeneration, spinal cord injury (SCI), dorsal root ganglia (DRG) transplantation, cortical neuron aggregates (CNAs), experimental modeling, axonal guidance, axonal bridging

DOI: 10.3233/RNN-190933

Citation: Restorative Neurology and Neuroscience, vol. 38, no. 1, pp. 1-9, 2020

Authors: Stoykov, Mary Ellen | King, Erin | David, Fabian J. | Vatinno, Amanda | Fogg, Louis | Corcos, Daniel M.

Article Type: Research Article

Abstract: Background: Bilateral priming, device assisted bilateral symmetrical wrist flexion/extension, is a noninvasive neuromodulation technique that can be used in the clinic. Objective: We examined the additive effect of bilateral motor priming and task specific training in individuals with severe upper limb hemiparesis. Methods: This is a parallel assignment, single-masked, randomized exploratory pilot study with three timepoints (pre-/post-intervention and follow up). Participants received either bilateral motor priming or health care education followed by task specific training. Sixteen participants who were at least 6 months post-stroke and had a Fugl Meyer Upper Extremity (FMUE) score between 23 and …38 were randomized. Our primary and secondary measures were Chedoke Arm & Hand Activity Index 9 (CAHAI-9) and the FMUE respectively. We determined changes in interhemispheric inhibition using transcranial magnetic stimulation. We hypothesized that improvement in the priming group would persist at follow up. Results: There was no between-group difference in the CAHAI. The improvement in the FMUE was significantly greater in the experimental group at follow up (t  = 2.241, p  = 0.045). Conclusions: Both groups improved in the CAHAI. There was a significant between-group difference in the secondary outcome measure (FMUE) where the bilateral priming group had an average increase of 10 points from pre-intervention to follow up. Show more

Keywords: Stroke, upper extremity, hemiparesis, priming, bilateral, task specific training, interhemispheric inhibition

DOI: 10.3233/RNN-190943

Citation: Restorative Neurology and Neuroscience, vol. 38, no. 1, pp. 11-22, 2020

Authors: Günther, Mattias | Sköld, Mattias K.

Article Type: Research Article

Abstract: Background: In a model of injured spinal motor neurons where the avulsed spinal nerve is surgically reimplanted, useful regrowth of the injured nerve follows, both in animal experiments and clinical cases. This has led to surgical reimplantation strategies with subsequent partial functional motoric recovery. Still, the ideal time point for successful regeneration after reimplantation and the specific genetic profile of this time point is not known. Objective: To explore the temporal gene expression of the whole genome in the ventral spinal cord after reimplantation at different time points after avulsion. Methods: Totally 18 adult rats were …subjected to avulsion of the left L5 root only (N = 3), avulsion followed by acute spinal reimplantation (N = 3), avulsion followed by 24 h (N = 3) or 48 h (N = 3) delayed reimplantation. Animals were allowed to survive 24 h after their respective surgery whereafter the ventral quadrant of the spinal cord at the operated side was harvested, processed for and analysed with Affymetrix Rat Gene ST 1.0 array followed by statistical analysis of gene expression patterns Results: Specific gene expression patterns were found at different time points after avulsion and reimplantation. Over all, early reimplantation seemed to diminish inflammatory response and support gene regulation related to neuronal activity compared to avulsion only or delayed reimplantation. In addition did gene activity after avulsion-reimplantation correspond to regeneration-associated genes typical for regeneration in the peripheral nervous system. Conclusions: Our study reveal that genetic profiling after this kind of injury is possible, that specific and distinct expression patterns can be found with early reimplantation being favourable over late and that regenerative activity in this kind of injury bears hallmark typical for peripheral nerve regeneration. These findings can be useful in elucidating specific genetic expression typical for successful nerve regeneration, hopefully not only in this specific model but in the nervous system in general. Show more

Keywords: Ventral root avulsion, ventral root reimplantation, spinal cord, nerve regeneration, gene expression, microarray

DOI: 10.3233/RNN-190955

Citation: Restorative Neurology and Neuroscience, vol. 38, no. 1, pp. 23-40, 2020

Authors: Jiang, Naifu | Wei, Jinsong | Li, Guangsheng | Wei, Bo | Zhu, Frank F. | Hu, Yong

Article Type: Research Article

Abstract: Background: Dry-electrode-based transcranial direct current stimulation is a new type of non-invasive brain stimulation system which relieves chronic low back pain and improves related muscle movement, in a way that overcomes the drawback of conventional systems. Objective: To investigate the effectiveness of dry-electrode-based transcranial direct current stimulation in relieving chronic low back pain and altering pain-related low back muscles movement, by using pain assessment tool and surface electromyographic topography. Methods: We conducted a prospective, double-blind, randomized, sham-controlled study. 60 patients with non-specific chronic low back pain were randomly and evenly allocated into tDCS and sham groups. …Each group accepted a single 20-minute stimulation at 2 mA on the primary motor cortex. Numeric rating scale for pain intensity assessment and root-mean-square difference parameter from surface electromyographic topography were measured before and after stimulation. The current direction in brain using finite element method was simulated to verify the current distribution under dry stimulation electrode. Results: After stimulation, the pain intensity in the tDCS group significantly decreased, while it did not show evident change in the sham group. However, change of root-mean-square difference parameters between tDCS and sham groups showed no significant difference. Simulation results based on finite element method showed most of current focused on primary motor cortex while peak value of current density was 0.225 A/m2 . Conclusions: Dry-electrode-based transcranial direct current stimulation can lower pain perception in patients with chronic low back pain. The analgesic mechanism can affect the top-down modulation pathway of pain. Show more

Keywords: Pain measurement, finite element analysis, analgesia, electrodes

DOI: 10.3233/RNN-190922

Citation: Restorative Neurology and Neuroscience, vol. 38, no. 1, pp. 41-54, 2020

Authors: Khedr, Eman M. | Mohamed, Khaled O. | Ali, Anwar M. | Hasan, Asmaa M.

Article Type: Research Article

Abstract: Background: The exact mechanism of cognitive impairment in PD is not known. Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a possible treatment for cognitive impairment and to treat the motor symptoms in Parkinson’s disease (PD) where its effects seem additive to those of dopaminergic medications. Objective: In this pilot study we investigated whether repeated sessions of rTMS have an effect on measures of cognitive impairment in patients with PD dementia. Methods: 33 patients with PD dementia were randomly assigned sham or real rTMS (2000 pulses; 20 Hz; 90% RMT; 10 trains of 10 s with 25 s …between each train) over the hand area of each motor cortex (5 min between hemispheres) for 10 days (5 days/week) followed by 5 booster sessions every month for 3 months. Assessments included the Unified Parkinson’s Disease Rating Scale part III (UPDRS), Montreal Cognitive Assessment (MoCA); Mini Mental State Examination (MMSE), Clinical Dementia Rating Scale (CDR); Memory and Executive Screening (MES) and Instrumental activity of Daily Living (IADL). Event related potentials (P300) and cortical excitability were measured before treatment and after the last session. Results: There were no significant differences in the effects of rTMS between groups. Although rTMS improved motor function in the active group it had only a minor effect on two of the dementia rating scores (the MMSE and MoCA) but not the others (CDR and MES). There was also a reduction in the latency of the P300 in the active group. Conclusions: rTMS over M1 is useful for motor function and may have a small positive effect on cognition. However, better approaches for the latter are necessary, may be require multisite rTMS to target both motor and frontal cortical region. Show more

Keywords: Parkinson’s disease, cognitive impairment, dementia, repetitive transcranial magnetic stimulations, Unified Parkinson’s Disease Rating Scale part III, Montreal cognitive assessment, Mini mental state examination, Clinical Dementia Rating, P300, cortical excitability parameters

DOI: 10.3233/RNN-190956

Citation: Restorative Neurology and Neuroscience, vol. 38, no. 1, pp. 55-66, 2020

Authors: Regenhardt, Robert W. | Takase, Hajime | Lo, Eng H. | Lin, David J.

Article Type: Review Article

Abstract: Stroke is among the most common causes of adult disability worldwide, and its disease burden is shifting towards that of a long-term condition. Therefore, the development of approaches to enhance recovery and augment neural repair after stroke will be critical. Recovery after stroke involves complex interrelated systems of neural repair. There are changes in both structure (at the molecular, cellular, and tissue levels) and function (in terms of excitability, cortical maps, and networks) that occur spontaneously within the brain. Several approaches to augment neural repair through enhancing these changes are under study. These include identifying novel drug targets, implementing rehabilitation …strategies, and developing new neurotechnologies. Each of these approaches has its own array of different proposed mechanisms. Current investigation has emphasized both cellular and circuit-based targets in both gray and white matter, including axon sprouting, dendritic branching, neurogenesis, axon preservation, remyelination, blood brain barrier integrity, blockade of extracellular inhibitory signals, alteration of excitability, and promotion of new brain cortical maps and networks. Herein, we review for clinicians recovery after stroke, basic elements of spontaneous neural repair, and ongoing work to augment neural repair. Future study requires alignment of basic, translational, and clinical research. The field continues to grow while becoming more clearly defined. As thrombolysis changed stroke care in the 1990 s and thrombectomy in the 2010 s, the augmentation of neural repair and recovery after stroke may revolutionize care for these patients in the coming decade. Show more

Keywords: Stroke, recovery, neural repair, translation

DOI: 10.3233/RNN-190978

Citation: Restorative Neurology and Neuroscience, vol. 38, no. 1, pp. 67-92, 2020

Authors: Hadanny, Amir | Rittblat, Mor | Bitterman, Mor | May-Raz, Ido | Suzin, Gil | Boussi-Gross, Rahav | Zemel, Yonatan | Bechor, Yair | Catalogna, Merav | Efrati, Shai

Article Type: Research Article

Abstract: Background: Previous studies have shown that hyperbaric oxygen therapy (HBOT) can improve the motor functions and memory of post-stroke patients in the chronic stage. Objective: The aim of this study is to evaluate the effects of HBOT on overall cognitive functions of post-stroke patients in the chronic stage. The nature, type and location of the stroke were investigated as possible modifiers. Methods: A retrospective analysis was conducted on patients who were treated with HBOT for chronic stroke (>3 months) between 2008-2018. Participants were treated in a multi-place hyperbaric chamber with the following protocols: 40 to 60 …daily sessions, 5 days per week, each session included 90 min of 100% oxygen at 2 ATA with 5 min air brakes every 20 minutes. Clinically significant improvements (CSI) were defined as > 0.5 standard deviation (SD). Results: The study included 162 patients (75.3% males) with a mean age of 60.75±12.91. Of them, 77(47.53%) had cortical strokes, 87(53.7%) strokes were located in the left hemisphere and 121 suffered ischemic strokes (74.6%). HBOT induced a significant increase in all the cognitive function domains (p  < 0.05), with 86% of the stroke victims achieving CSI. There were no significant differences post-HBOT of cortical strokes compared to sub-cortical strokes (p  > 0.05). Hemorrhagic strokes had a significantly higher improvement in information processing speed post-HBOT (p  < 0.05). Left hemisphere strokes had a higher increase in the motor domain (p  < 0.05). In all cognitive domains, the baseline cognitive function was a significant predictor of CSI (p  < 0.05), while stroke type, location and side were not significant predictors. Conclusions: HBOT induces significant improvements in all cognitive domains even in the late chronic stage. The selection of post-stroke patients for HBOT should be based on functional analysis and baseline cognitive scores rather than the stroke type, location or side of lesion. Show more

Keywords: HBOT, stroke, cognitive function, hyperbaric oxygen

DOI: 10.3233/RNN-190959

Citation: Restorative Neurology and Neuroscience, vol. 38, no. 1, pp. 93-107, 2020

Authors: Meng, Ying | Zhang, Dai | Hai, Hong | Zhao, Ying-Yu | Ma, Yue-Wen

Article Type: Research Article

Abstract: Background: Both 1 Hz repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) are reported to benefit upper limb motor function rehabilitation in patients with stroke. However, the efficacy of combining 1 Hz rTMS and iTBS has not been adequately explored. Objective: We aimed to compare the effects of 1 Hz rTMS and the combination of 1 Hz rTMS and iTBS on the upper limb motor function in the subacute phase post-stroke. Methods: Twenty-eight participants were randomly assigned to three groups: Group A (1 Hz rTMS over the contralesional primary motor cortex (M1) and iTBS over the ipsilesional M1), Group …B (contralesional 1 Hz rTMS and ipsilesional sham iTBS), and Group C (contralesional sham 1 Hz rTMS and ipsilesional sham iTBS). The participants received the same conventional rehabilitation accompanied by sessions of transcranial magnetic stimulation for two weeks (5 days one week). Motor-evoked potential (MEP), upper extremity Fugl-Meyer Assessment (UE-FMA), and Barthel Index (BI) were performed before and after the sessions. Results: Group A showed greater UE-FMA, BI, and MEP amplitude improvement and more significant decrement in MEP latency compared to Group B and Group C in testable patients. Correlation analyses in Group A revealed a close relation between ipsilesional MEP amplitude increment and UE-FMA gain. Conclusions: The combining of 1 Hz rTMS and iTBS protocol in the present study is tolerable and more beneficial for motor improvement than the single use of 1 Hz rTMS in patients with subacute stroke. Show more

Keywords: Transcranial magnetic stimulation, stroke, rehabilitation

DOI: 10.3233/RNN-190953

Citation: Restorative Neurology and Neuroscience, vol. 38, no. 1, pp. 109-118, 2020