Restorative Neurology and Neuroscience - Volume 31, issue 4

Authors: Szaflarski, Jerzy P. | Allendorfer, Jane B. | Banks, Christi | Vannest, Jennifer | Holland, Scott K.

Article Type: Research Article

Abstract: Purpose: Several adult studies have documented the importance of the peri-stroke areas to aphasia recovery. But, studies examining the differences in patterns of cortical participation in language comprehension in patients who have (LMCA-R) or have not recovered (LMCA-NR) from left middle cerebral artery infarction have not been performed up to date. Methods: In this study, we compare cortical correlates of language comprehension using fMRI and semantic decision/tone decision task in 9 LMCA-R and 18 LMCA-NR patients matched at the time of stroke for age and handedness. We examine the cortical correlates of language performance by correlating intra- and extra-scanner measures …of linguistic performance with fMRI activation and stroke volumes. Results: Our analyses show that LMCA-R at least 1 year after stroke show a return to typical fMRI language activation patterns and that there is a compensatory reorganization of language function in LMCA-NR patients with shifts to the right hemispheric brain regions. Further, with increasing strength of the left-hemispheric fMRI signal shift there are associated improvements in performance as tested with standardized linguistic measures. A negative correlation between the size of the stroke and performance on some of the linguistic tests is also observed. Conclusions: This right-hemispheric shift as a mechanism of post-stroke recovery in adults appears to be an ineffective mode of language function recovery with increasing right-hemispheric shift associated with lower language performance. Thus, normalization of the post-stroke language activation patterns is needed for better language performance while shifts of the activation patterns to the non-dominant (right) hemisphere and/or large stroke size are associated with decreased linguistic abilities after stroke. Show more

Keywords: Functional MRI, aphasia, language, recovery, semantic decision, stroke

DOI: 10.3233/RNN-120267

Citation: Restorative Neurology and Neuroscience, vol. 31, no. 4, pp. 347-360, 2013

Authors: de Diego, Cristina | Puig, Silvia | Navarro, Xavier

Article Type: Research Article

Abstract: Purpose: The hypothesis of this study is that intensive therapy by means of a sensory and motor stimulation program of the upper limb in patients with chronic hemiparesis and severe disability due to stroke increases mobility and sensibility, and improves the use of the affected limb in activities of daily living (ADL). Methods: The program consists of 16 sessions of sensory stimulation and functional activity training in the rehabilitation center, and daily sessions of tactile stimulation, mental imaginery and practice of ADL at home, during 8 weeks. An experimental group (EG) of 12 patients followed this program, compared with a …control group (CG) of 9 patients under standard rehabilitation. The efficacy of the program was evaluated by Fugl Meyer Assessment (FMA), Motor Activity Log (MAL) and Stroke Impact Scale-16 (SIS-16) scores, and a battery of sensory tests. Results: The results show that in both groups, the motor FMA and the SIS-16 improved during the 8 weeks, this improvement being higher in the EG. Significant improvements were observed for the sensory tests in the EG. Conclusion: The intensive sensorimotor stimulation program for the upper extremity may be an efficacious method for improving function and use of the affected limb in ADL in chronic stroke patients. Show more

Keywords: Rehabilitation, stroke, sensorimotor stimulation, upper limb, constraint therapy, chronic paralysis

DOI: 10.3233/RNN-120250

Citation: Restorative Neurology and Neuroscience, vol. 31, no. 4, pp. 361-371, 2013

Authors: Romano, Daniele | Bottini, Gabriella | Maravita, Angelo

Article Type: Research Article

Abstract: Background and Purpose: The mirror box (MB) was developed in the early 1990 s to relieve phantom limb sensations and chronic pain. Although its efficacy has been shown in several clinical populations, the mechanisms underpinning effects still have to be fully understood. Methods: 48 healthy subjects participated in 4 behavioral experiments where kinesthetic sensitivity of the hand inside the MB was tested during the observation of mirror-reflected finger movements, executed with the hand outside the MB. Results: We identified two effects on the hand hidden inside the MB: diminished kinesthetic sensitivity for passive movements, and the occurrence of unconscious, involuntary …movements with the finger inside the box, suggesting reduced motor awareness. Such sensory-motor effects were somatotopically specific to the finger moved, were influenced by the contextual presence of the whole hand in the mirror, and occurred for both active and passive movements of the hand outside the MB. Conclusions: The present results suggest that the MB induce a somatotopically and contextually specific overriding of kinesthetic control by vision, compatible with a process of embodiment of the mirror-reflected hand image and provide novel clues to the understanding of the mechanisms underlying MB effects. Show more

Keywords: Mirror box, embodiment, body representation, d-prime, mirror visual feedback, mirror therapy

DOI: 10.3233/RNN-120273

Citation: Restorative Neurology and Neuroscience, vol. 31, no. 4, pp. 373-386, 2013

Authors: Marumoto, Kohei | Koyama, Tetsuo | Hosomi, Masashi | Takebayashi, Takashi | Hanada, Keisuke | Ikeda, Sayaka | Kodama, Norihiko | Domen, Kazuhisa

Article Type: Research Article

Abstract: Purpose: To test whether diffusion tensor imaging could evaluate potential motor capability of patients with chronic cerebral infarction. Methods: We used constraint-induced movement therapy (CIMT) as a rehabilitation, which reveals potential motor capability. We also investigated the relationship between the outcome of CIMT and the ratio between fractional anisotropy values (rFA) in affected and unaffected sites of the corticospinal tract before CIMT. Imaging was performed in cerebral infarction patients (n = 14) and the rFA of the posterior limb of internal capsule (PLIC) was measured before CIMT. Patients were evaluated before and after CIMT using the Fugl-Meyer (F-M) assessment, Wolf …Motor Function Test, Action Research Arm Test, and Motor Activity Log and association between PLIC- rFA and these scores was determined. Results: All patients showed an improvement in mobility following the 10-day CIMT session. Strong positive correlation was found only between F-M after CIMT and PLIC-rFA (r = 0.8098, p = 0.0004). A strong linear relationship was observed after CIMT. Conclusion: These data support PLIC-rFA as a new marker of the CIMT-induced improvement in motor function (F-M). Show more

Keywords: Constraint-induced movement therapy, rehabilitation, stroke, diffusion tensor imaging, fractional anisotropy, corticospinal tract

DOI: 10.3233/RNN-120285

Citation: Restorative Neurology and Neuroscience, vol. 31, no. 4, pp. 387-396, 2013

Authors: Min, Kyunghoon | Song, Junyoung | Lee, Ji Hyun | Kang, Myung Seo | Jang, Su Jin | Kim, Sang Heum | Kim, MinYoung

Article Type: Research Article

Abstract: Objective: To report the safety and efficacy of a novel therapeutic trial with umbilical cord blood (UCB) and concomitant recombinant human erythropoietin (rhEPO), which was tried for three cases of severe traumatic brain injury (TBI) in rehabilitation. Design: Case series. Setting: University hospital setting. Participants: Three patients with TBI over 6-months post-injury. Interventions: Intravascular administration of allogenic UCB and injection of rhEPO, and rehabilitation therapy. Outcomes: For safety, adverse events, symptom, vital signs, blood chemistry, and hematologic study; for efficacy, modified Barthel index, motor assessment scale, Fugl-Meyer assessment of upper extremity, motor-free visual perception test, mini-mental screening examination, and brain …images. Results: There were no serious adverse events and the participants showed improvements during the follow-up periods in various aspects. Patient 1 demonstrated improvements in motor and cognitive function. Diffusion tensor images showed increased nerve fibers. Patient 2 displayed improvements in activities of daily living. In Patient 3, neurogenic fever vanished and Brain PET revealed increased glucose metabolism at basal ganglia, thalami, and cerebellum. Conclusions: The allogenic UCB therapy combined with rhEPO in the present study was safe and suggested potential therapeutic efficacy for patients with TBI. Controlled clinical trials are now needed to document efficiacy and safety in a larger patient sample. Show more

Keywords: Umbilical cord blood, erythropoietin, safety, efficacy, traumatic brain injury

DOI: 10.3233/RNN-120289

Citation: Restorative Neurology and Neuroscience, vol. 31, no. 4, pp. 397-410, 2013

Authors: Redondo-Castro, Elena | García-Alías, Guillermo | Navarro, Xavier

Article Type: Research Article

Abstract: Purpose: Spinal cord injuries (SCI) cause motor, sensory and autonomic dysfunctions as well as neuropathic pain. We investigated plastic changes occurring in cord segments caudal to the lesion to assess their potential contribution to pain states after SCI. Methods: Different thoracic SCIs were performed in adult rats. Functional and algesimetry tests were performed along 3 months. Several elements of the spinal nociceptive circuitry were assessed by immunohistochemical analyses of lumbar segments. Results: Injured animals manifested mechanical and thermal hyperalgesia. Wind-up responses and spinal reflexes were enhanced, indicating spinal hyperexcitability. We found an increase in density of nociceptive sensory afferences and …in GABA inhibitory activity in dorsal horns, and increased glial reactivity. Serotoninergic descending fibers and contacts on ventral horn motoneurons were reduced. Motoneurons presented more abundant inhibitory inputs, identified by gephyrin. Not all the changes kept direct relationship to the severity of the injury. Conclusion: The existence of hyperalgesia despite the boost of inhibitory elements in the spinal cord confirms the dysbalance between excitatory and inhibitory mechanisms, leading to a general disinhibition. Widespread dysfunctions in remote segments after central injuries contribute to the appearance of pain, and they may be new targets for therapies aimed to modulate spinal dysfunctions after injury. Show more

Keywords: Neuropathic pain, spinal cord injury, disinhibition, hyperreflexia, plasticity

DOI: 10.3233/RNN-120291

Citation: Restorative Neurology and Neuroscience, vol. 31, no. 4, pp. 411-430, 2013

Authors: Peruzzaro, Sarah T. | Gallagher, Jonathan | Dunkerson, Jacob | Fluharty, Sarah | Mudd, David | Hoane, Michael R. | Smith, Jeffrey S.

Article Type: Research Article

Abstract: Purpose: The effectiveness of embryonic stem cell (eSC) therapy has been explored in many models of neurological disease and several research groups have shown that eSC treatment leads to improved outcomes in pre-clinical models of traumatic brain injury (TBI). Though functional recovery occurs, few surviving eSCs appear to develop neuronal characteristics; instead the majority of the surviving eSC express glial phenotypes. Additionally, researchers have shown that enriching the post-surgical environment of the subject promotes functional recovery following TBI. The purpose of the current project was to determine if post-surgical environmental enrichment (EE) impacts the survival, migration, and integration of eSCs …in a rodent model of TBI and if the presence of these cells lead to improved outcomes. Methods: In the current study, the medial frontal cortex (MFC) of rats was injured using a controlled cortical impact (CCI) device. Immediately following injury the rats were placed into either EE or standard environment (SE) housing and then seven days post-injury rats received either murine cortical eSC or media. Behavioral testing consisted of the Morris water maze (MWM), Barnes Maze (BM), and Rotarod tasks (RR). Results: On the MWM task, TBI/eSC/EE animals performed as well as the Sham/SE and Sham/EE groups. The TBI/eSC/SE, TBI/Media/EE, and TBI/Media/SE groups were impaired compared to the controls. By the end of training on the BM there were no differences between the Sham, TBI/Media/EE, and TBI/eSC/EE groups. On the RR task all animals placed in the EE performed equally well and significantly better than their SE housed counterparts. By the end of training on the RR task, the TBI/eSC/EE group performed as well as the sham counterparts, and though not significant they also surpassed the performance of the injured animals that received enrichment or eSC treatment alone. Conclusions: Combing therapeutic strategies with enriching the post-injury environment is likely to be an important addition to determining the efficacy of pre-clinical therapies. Show more

Keywords: Traumatic brain injury, recovery of function, CCI, embryonic stem cells, enriched environment

DOI: 10.3233/RNN-120299

Citation: Restorative Neurology and Neuroscience, vol. 31, no. 4, pp. 431-450, 2013

Authors: Robinson, Grant A. | Madison, Roger D.

Article Type: Research Article

Abstract: Purpose: After a cut peripheral nerve is repaired, motor neurons usually regenerate across the lesion site, however they often enter an inappropriate Schwann cell tube and may be directed to an inappropriate target organ such as skin, resulting in continued loss of function. In fact, only about 10% of adults who receive a peripheral nerve repair display full functional recovery. The reasons for this are many and complex, however one aspect is whether the motor neuron has undergone a prolonged period of axotomy prior to nerve repair. Previous studies have suggested a deleterious effect of prolonged axotomy. Methods: We examined …the influence of prolonged axotomy on target selectivity using a cross-reinnervation model of rat obturator motor neurons regrowing into the distal femoral nerve, with its normal bifurcating pathways to muscle and skin. Results: Surprisingly, we found that a prolonged period of axotomy resulted in an increase in motor neuron regeneration accuracy. In addition, we found that regeneration accuracy could be increased even further by a simple surgical manipulation of the distal terminal nerve pathway to skin. Conclusions: These results suggest that under certain conditions prolonged axotomy may not be detrimental to the final accuracy of motor neuron regeneration and highlight that a simple manipulation of terminal nerve pathways may be one approach to increase such regeneration accuracy. Show more

Keywords: Pathway choice, obturator nerve, femoral nerve, regeneration, delayed repair

DOI: 10.3233/RNN-120301

Citation: Restorative Neurology and Neuroscience, vol. 31, no. 4, pp. 451-460, 2013

Authors: Sun, Chong-ran | Chen, Zheng-he | Yin, Si-yuan | Chen, Sheng | Hong, Yuan | Yan, Wei | Zhang, Jian-min

Article Type: Research Article

Abstract: Purpose: How injured long-distance neural tracts are reestablished following ischemic brain injury remains unclear. Theories surrounding reconnection include the growth of newly formed axons from newborn neurons, modification of local circuits and a beneficial influence from neurotrophic factors. This research aimed to find the developing new born neurons and the neurotrophic factors they secreted in a middle cerebral artery occlusion (MCAO) rat model to explain the roles of neural progenitor cells in post-ischemic neurogenesis. Methods: Fifty-three male Sprague-Dawley rats underwent the MCAO procedure or sham operation. Double labeling of specific neuron markers (calbindin and N-200) and a dividing cell marker …(BrdU) were used to identify newly formed neurons. Neurotrophic factors were examined in the cerebrospinal fluid in post-ischemic rats using enzyme-linked immunosorbent assay. Results: Ischemic injury induced activation of neurogenesis. The newborn neurons differentiated into calbindin-positive interneurons, but not N-200 positive projection neurons. The concentration of neurotrophic factors was elevated and was in accordance with the neurogenesis seen in ischemic animal models. Conclusion: Our research indicates that the recovery of neural function is not ascribed to the reestablishment of damaged projection tracts, but to the modulation of local circuits and beneficial effects of neurotrophins produced by neural progenitor cells. Show more

Keywords: Neurogenesis, interneuron, projection neuron, ischemia, neurotrophic factors

DOI: 10.3233/RNN-120306

Citation: Restorative Neurology and Neuroscience, vol. 31, no. 4, pp. 461-472, 2013

Authors: Kotchoubey, B. | Veser, S. | Real, R. | Herbert, C. | Lang, S. | Kübler, A.

Article Type: Research Article

Abstract: Purpose: To analyze the principles that guide inference of covert cognitive functions and consciousness in patients with extremely severe brain damage on the basis of neurophysiological test results. Methods: (1) A quantitative analysis of a range of possible inferences based on neurophysiological findings in low- and non-responsive patients; (2) a logical analysis of the various possible orders of application of neurophysiological tests in such patients. Results: Surprisingly, improvement of neurophysiological test qualities contributes to the improvement of diagnostic results less than some other factors, such as the structure of the patient population, the quality of the previous clinical diagnosis, and …the variability of the methods used. Conclusions: A sequential decision procedure is suggested. Different test paradigms should be combined most effectively to arrive at a reliable evaluation of cognitive functions in this patient population. Show more

Keywords: Cognition, consciousness, minimally conscious state, negative prediction, neurophysiological assessment, non-responsive patients, unresponsive wakefulness syndrome, vegetative state

DOI: 10.3233/RNN-120307

Citation: Restorative Neurology and Neuroscience, vol. 31, no. 4, pp. 473-485, 2013

Authors: Wang, Jiangbi | Feng, Xiang | Du, Yi | Wang, Lei | Zhang, Shengxiang

Article Type: Research Article

Abstract: Purpose: The present study was aimed to investigate whether combination treatment with progesterone and rehabilitation training would be more effective than monotherapy after cerebral ischemia. Methods: C57BL/6 mice were subjected to focal ischemia by photothrombosis and were treated with progesterone (2 mg/kg), rehabilitation training or their combination. 2,3,5-triphenyltetrazolium chloride (TTC) staining and Nissl staining were used to measure infarct size at day 3 and day 7 after surgery, and rotarod test and grip strength test were conducted to evaluate behavioral outcomes. Results: TTC staining indicated that progesterone, rehabilitation training and their combination produced a different degree of reduction in infarct …volume compared with vehicle control at day 3 after ischemia (progesterone: 16.70 ± 0.93 mm3 , p < 0.01, rehabilitation training: 22.19 ± 0.93 mm3 , p < 0.05, progesterone + rehabilitation training: 14.76 ± 0.92 mm3 , p < 0.01, vehicle control: 28.73 ± 1.05 mm3 ). Nissl staining revealed that prolonged treatment of progesterone, rehabilitation training and their combination led to a significant decrease in infarct volume at day 7 after ischemia (progesterone: 18.64 ± 1.83 mm3 , p < 0.01, rehabilitation training: 25.07 ± 1.70 mm3 , p < 0.05, progesterone + rehabilitation training: 17.09 ± 0.92 mm3 , p < 0.01, vehicle control: 30.31 ± 1.36 mm3 ). No accumulative effect in the reduction of infarct volume was observed in combination therapy at both day 3 and day 7 after ischemia. However, combination therapy significantly improved behavioral performances in the first week after photothrombosis. Combination treatment significantly enhanced rotarod performance and forelimb grip strength at all time points within 7 days after ischemia compared with rehabilitation alone, and significantly improved rotarod performance and forelimb grip strength from day 2 after ischemia compared with progesterone alone. Conclusion: Our results suggested that combination treatment with progesterone and rehabilitation training had no additive effect in reducing infarct volume, but combination therapy exhibited enhanced efficacy in promoting functional recovery after ischemic stroke, suggesting progesterone and rehabilitation training may exert their effects via different mechanisms. Show more

Keywords: Progesterone, rehabilitation training, ischemic stroke, infarct, functional recovery

DOI: 10.3233/RNN-130312

Citation: Restorative Neurology and Neuroscience, vol. 31, no. 4, pp. 487-499, 2013

Authors: Torres, Jose | Drebing, Daniel | Hamilton, Roy

Article Type: Research Article

Abstract: Aphasia is a common result of stroke, affecting over one million Americans. Currently, intensive speech therapy is the mainstay of treatment, although its efficacy has been variable at best. Recent years have seen the emergence of non-invasive brain stimulation, specifically Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS), as potential treatments for post-stroke aphasia. A growing body of investigations has shown the efficacy of both modalities in facilitating recovery from chronic aphasia, while data regarding subacute aphasia are much more limited and evidence in the acute post-stroke phase are still lacking. Much remains unknown about how these techniques …cause clinical improvement or about their long-term efficacy, side-effects, and safety. In this article, we examine the data demonstrating the safety and efficacy of TMS and tDCS, discuss the major differences between them, and consider how those differences may inform the use of each modality. We also consider the different models of neuroplasticity in the setting of post-stroke aphasia and how these models may influence when and in which patients each modality would impart the most benefit. Show more

Keywords: Transcranial Magnetic Stimulation (TMS), Transcranial Direct Current Stimulation (tDCS), aphasia, neuroplasticity, stroke

DOI: 10.3233/RNN-130314

Citation: Restorative Neurology and Neuroscience, vol. 31, no. 4, pp. 501-515, 2013