Restorative Neurology and Neuroscience - Volume 25, issue 5-6

Authors: Wolf, Steven L. | Newton, Heather | Maddy, Douglas | Blanton, Sarah | Zhang, Qin | Winstein, Carolee J. | Morris, David M. | Light, Kathye

Article Type: Research Article

Abstract: Purpose: To examine the relationship between change scores on the log mean Wolf Motor Function Test (lmWMFT) and the intensity of supervised Constraint Induced Movement Therapy (CIMT) in participants with subacute and chronic stroke. Methods: A retrospective analysis of data from 169 EXCITE participants who received CIMT either immediately after randomization or one year later was undertaken. During waking hours, participants wore a restraining mitt on the less affected extremity. The lmWMFT was administered …before and after the two week treatment block. Results: Significant relationships were seen between the intensity of training and functional score in the immediate, lower functional group for whom more training in adaptive task practice resulted in poorer outcomes (p=0.01) and in the immediate, higher functioning group for whom more training in repetitive task practice resulted in poorer outcomes (p=0.02). Female participants in the immediate group showed less progress in lmWMFT scores with greater amounts of total training (p=0.01). Functional level, gender, and concordance did not modify any other relationship. Both higher functioning participants who trained within the normal ratio (N=50) and who were exposed to more than the prescribed adaptive task practice (N=11) experienced a significant improvement in the lmWMFT score (p=0.03 and p=0.02, respectively) compared to those higher functioning participants who experienced excessive repetitive task practice. Conclusion: Applying CIMT to a large sample of participants with stroke resulted in directionally inappropriate but significant relationships between intensity and lmWMFT scores in the immediate but not the delayed group. Our data also suggest that functional improvements observed in the EXCITE Trial might be attributable to training components other than the designated ratio of training approaches (adaptive and repetitive task practice). Show more

Keywords: Stroke, constraint-induced therapy, intensity, rehabilitation, wolf motor function test, adaptive/shaping task practice

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 5-6, pp. 549-562, 2007

Authors: Mueller, Iris | Mast, Henning | Sabel, Bernhard A.

Article Type: Research Article

Abstract: Purpose: In small experimental trials, vision restoration therapy (VRT), a home-based rehabilitation method, has shown to enlarge the visual field and improve reaction times in patients with lesion involving the CNS. We now evaluated the outcome of VRT in a large sample of clinical patients and studied factors contributing to subjective and objective measures of visual field alterations. Methods: Clinical observational analysis of visual fields of 302 patients before and after being treated with …computer-based vision restoration therapy for a period of 6 months at eight clinical centers in central Europe. The visual field defects were due to ischemia, hemorrhage, head trauma, tumor removal or anterior ischemic optic neuropathy. Primary outcome measure was a visual field assessment with super-threshold perimetry. Additionally, conventional near-threshold perimetry, eye movements and subjective reports of daily life activities were assessed in a subset of the patients. Results: VRT improved patients' ability to detect super-threshold stimuli in the previously deficient area of the visual field by 17.2% and these detection gains were not significantly correlated with eye movements. Notable improvements were seen in 70.9% of the patients. Efficacy was independent of lesion age and etiology, but patients with larger areas of residual vision at baseline and patients > 65 years old benefited most. Conventional perimetry validated visual field enlargements and patient testimonials confirmed the improvement in every day visual functions. Conclusions: VRT improves visual functions in a large clinical sample of patients with visual field defects involving the CNS, confirming former experimental studies. Show more

Keywords: Vision restoration, hemianopia, visual field deficits, plasticity, neurorehabilitation, visual training, brain damage

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 5-6, pp. 563-572, 2007

Authors: DeLucia, Tracey A. | Alexander, Thomas D. | Fargo, Keith N. | Jones, Kathryn J.

Article Type: Research Article

Abstract: Purpose: βII-tubulin, a regeneration-associated gene, is upregulated in injured peripheral neurons, but significantly less so in injured central neurons. Using a hamster dorsal spinal cord injury (SCI), the ability of single versus combinatorial treatment strategies to alter βII-tubulin mRNA expression in rubrospinal motoneurons (RSMN) was examined. We have shown that systemic testosterone propionate (TP) treatment in combination with peripheral nerve grafting into a SCI site produces a peripheral-like pattern of βII-tubulin mRNA …expression in injured RSMN. In the present study, selected single- and combinatorial-therapy strategies were tested for their ability to promote a sustained upregulation of βII-tubulin mRNA levels in injured RSMN. Methods: Single treatments of olfactory ensheathing cells (OEC), brain-derived neurotrophic factor (BDNF), or Schwann cells (SC) vs combinatorial treatments (SC + TP, OEC + TP, and OEC + BDNF) were administered to hamsters following a dorsal SCI. Quantitative in situ hybridization in conjunction with a βII-tubulin cDNA probe was accomplished. Results: All of the single-therapy treatments tested were able to prevent the downregulation of βII-tubulin mRNA that occurred a week after injury alone, but only BDNF maintained high levels of βII-tubulin mRNA. In contrast, all combinatorial treatments tested maintained the upregulation of βII-tubulin mRNA expression in injured RSMN 1 week post-SCI. Conclusions: Targeting both intrinsic and extrinsic components of CNS injury can re-program elements of the molecular response of injured central motoneurons. Show more

Keywords: Red nucleus, spinal cord injury, olfactory ensheathing cell, Schwann cell, BDNF

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 5-6, pp. 573-584, 2007

Authors: Hendriks, William T.J. | Eggers, Ruben | Carlstedt, Thomas P. | Zaldumbide, Arnaud | Tannemaat, Martijn R. | Fallaux, Frits J. | Hoeben, Rob C. | Boer, Gerard J. | Verhaagen, Joost

Article Type: Research Article

Abstract: Purpose: Spinal root avulsions result in paralysis of the upper and/or lower extremities. Implanting a peripheral nerve bridge or reinsertion of the avulsed roots in the spinal cord are surgical strategies that lead to some degree of functional recovery. In the current study lentiviral (LV) vector-mediated gene transfer of a green fluorescent protein (GFP) reporter gene was used to study the feasibility of gene therapy in the reimplanted root to further promote regeneration of motor axons. …Methods: A total of 68 female Wistar rats underwent unilateral root avulsion of the L4, L5 and L6 ventral lumbar roots. From 23 rats intercostal nerves were dissected before ventral root avulsion surgery, injected with a lentiviral vector encoding GFP (LV-GFP) and inserted between the spinal cord and avulsed rootlet. In the remaining 45 rats, the avulsed ventral root was injected with either LV-GFP or a lentiviral vector encoding a fusion between a GlyAla repeat and GFP (LV-GArGFP), and reinserted into the spinal cord. Expression of GFP was evaluated at 1, 2, 4 and 10 weeks, and one group at 4 months. Results: LV-GFP transduction of either nerve implants or reimplanted ventral roots revealed high GFP expression during the first 2 post-lesion weeks, but virtually no expression at 4 weeks. Since this reduction coincided with the appearance of mononuclear cells at the repair site, an immune response against GFP may have occurred. In a subsequent experiment reimplanted ventral roots were transduced with a vector encoding GFP fused with the GlyAla repeat of Epstein-Barr virus Nuclear Antigen 1 known to prevent generation of antigenic peptides from transgene products. Expression of this "stealth" gene persisted for at least 4 months in the reimplanted root. Conclusion: Thus persistent transgene expression can be achieved with non-immunogenic transgene products in reimplanted ventral roots. This demonstrates the feasibility of combining neurosurgical repair with LV vector-mediated gene therapy. The current approach will be used in future experiments with LV vectors encoding neurotrophic factors to enhance the regeneration of spinal motor neurons after traumatic avulsion of spinal nerve roots. Show more

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 5-6, pp. 585-599, 2007

Authors: Dow, Douglas E. | Cederna, Paul S. | Hassett, Cheryl A. | Dennis, Robert G. | Faulkner, John A.

Article Type: Research Article

Abstract: Purpose: Prolonged denervation of skeletal muscles results in atrophy and poor recovery of motor function following delayed reinnervation. Electrical stimulation reduces denervation atrophy. We hypothesized that electrical stimulation of denervated extensor digitorum longus (EDL) muscles during a prolonged period between nerve axotomy and opportunity for reinnervation by motoneurons after nerve-repair would enhance the recovery of muscle mass, force and motor-function. Methods: The EDL muscles of rats were denervated for 3.5 …months by peroneal nerve axotomy, then repaired with an end-to-end neurorrhaphy, and allowed to recover for 6.5 months. During the period of denervation, some of the rats received a protocol of electrical stimulation that had previously been shown to dramatically attenuate the effects of denervation atrophy through 4 months. Other experimental groups included unoperated control muscles, denervated muscles, and axotomy followed immediately by nerve-repair. Final evaluations included walking track analysis, maximum force measured in situ by indirect stimulation of the nerve, and muscle mass. Results: The hypothesis was not supported. Electrical stimulation during the period of denervation did not enhance recovery of muscle mass, force or motor function. Conclusion: The primary factors that inhibited reinnervation and recovery following delayed reinnervation were not alleviated by the electrical stimulation during the period of muscle denervation. Show more

Keywords: Contractile activity, walking track, neurorrhaphy, extensor digitorum longus, motor function, nerve repair

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 5-6, pp. 601-610, 2007

Authors: Krause, Phillip | Szecsi, Johann | Straube, Andreas

Article Type: Other

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 5-6, pp. 611-612, 2007