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

Authors: Sabel, B.A. | Matzke, S. | Prilloff, S.

Article Type: Research Article

Abstract: The journal Restorative Neurology and Neuroscience (RNN) is now published in its 25th volume since its inception in 1989. RNN focuses on the emerging field of brain plasticity, repair and rehabilitation, including original and review papers both in basic research (animal experiments, in vitro studies) and in the clinical domain, including brain imaging studies. During the last decade RNN has experienced a steady progress in its reference value and scientific impact. The ISI-impact …factor has risen from 1.117 (1997) to 2.862 (2006). This places the journal at the 81st rank among all 200 neuroscience journals, i.e. 60% of all neuroscience journals have a lower impact factor. When compared to other journals in the field of rehabilitation, RNN ranks number 1. Causes for this positive development are, among others: (1) the field of neuroplasticity, regeneration, recovery and rehabilitation is an emerging field in medicine and therefore the number of publications and their citation rate overall increases, (2) the special issues strategy, (3) a top level editorial board, and (4) the quality of papers submitted to RNN continuously improves as RNN is gaining increasing acceptance in the scientific community. Thus, in the space of neuroscience in general, and rehabilitation in particular, RNN has become a visible, high impact journal and a leading source of original scientific information pertaining to brain plasticity , rehabilitation and repair. RNN is likely to gain more momentum as the field matures further. Show more

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 5-6, pp. 445-451, 2007

Authors: Kwakkel, Gert | Kollen, Boudewijn

Article Type: Research Article

Abstract: Purpose: A number of longitudinal studies show that about one third of all patients regain dexterity following a stroke. However, the determinants of improvement of upper limb function are largely unknown. The aim of the present study was to investigate the longitudinal relationship of functional change in the upper paretic limb and change in time-dependent covariates in order to develop a multivariable regression model to predict improvement in dexterity. Methods: Based on 18 repeated measurements over time during …the first post-stroke year, 101 stroke patients with first-ever ischemic middle cerebral artery strokes were investigated. Baseline characteristics as well as longitudinal information from Action Research Arm Test (ARAT), Fugl-Meyer arm and hand score (FM-arm and FM-hand), Motricity Index arm and leg score (MI-arm and MI-leg), letter cancellation task (LCT), Fugl-Meyer balance score (FM-balance) and progress of time were obtained prospectively. Outcome constituted of change scores on the ARAT over first year post stroke. Adjoining measurements of time-dependent variables were used to calculate time-dependent changes producing change scores. Results: In total 1570 of the 1717 change scores were available for longitudinal regression analysis. The regression model shows that FM-hand change scores was the most important relative factor in predicting improvement on ARAT (standardized β=0.357; p< 0.001) followed by change scores on FM-arm (β = 0.007; p< 0.001), whereas progress of time was significantly negatively associated with improvement on ARAT (β = −0.001; p< 0.001). Conclusions: Functional improvement of the upper paretic limb is mainly determined by improvement of the paretic hand, followed by synergistic independent movement of the paretic arm. Progress of time itself is an independent covariate that is negatively associated with upper limb function suggesting that most pronounced improvements occur earlier after stroke. Show more

Keywords: Cerebrovascular accident, upper extremity, prognosis, multi-level modeling

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 5-6, pp. 453-460, 2007

Authors: Liepert, Joachim | Zittel, Simone | Weiller, Cornelius

Article Type: Research Article

Abstract: Purpose: Increasing evidence suggests that the contralesional motor cortex (M1) inhibits the ipsilesional M1 in stroke patients. This inhibition could impair motor function of the affected hand. We investigated if inhibitory 1~Hz repetitive transcranial magnetic stimulation (rTMS) over the contralesional M1 improved motor performance of the affected hand in acute stroke. Methods: A double-blind study of real versus placebo rTMS was conducted. Twelve patients early after subcortical stroke (mean: 7 days) …received 1200 stimuli of real and placebo rTMS in a crossover design. The sequence of stimulations was counterbalanced across subjects. Stimulus intensity was subthreshold (90% of motor threshold at rest). Motor function was tested by grip strength recordings and Nine Hole Peg Test (NHPT) executions before and after each rTMS session. Results: Compared to sham stimulation, real rTMS improved NHPT results but not grip strength in the affected hand. No change of performance was observed for the unaffected hand. NHPT baseline repetitions in a subgroup of patients indicated stable motor performance prior to the rTMS sessions. Conclusions: The study suggests that therapeutic rTMS applications over the contralesional hemisphere are feasible in acute stroke patients and can transiently improve dexterity of the affected hand. RTMS may become an additional tool for early neurorehabilitation. Show more

Keywords: Repetitive transcranial magnetic stimulation, stroke, dexterity

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 5-6, pp. 461-465, 2007

Authors: Buchhold, B. | Mogoanta, L. | Suofu, Y. | Hamm, A. | Walker, L. | Kessler, Ch. | Popa-Wagner, A.

Article Type: Research Article

Abstract: Purpose: Aging is associated with a temporally dysregulated cellular response to ischemia as well as poor functional recovery. While environmental enrichment has been shown to improve the behavioral outcome of stroke in young animals, the effect of an enriched environment on behavioral and neuropathological recovery in aged animals is not known. Methods: Focal cerebral ischemia was produced by electrocoagulation of the right middle cerebral artery in 3 month- and 20 month-old male Sprague-Dawley rats. The …functional outcome was assessed in neurobehavioral tests conducted over a period of 28 days following surgery. Brain tissue was then immunostained for proliferating astrocytes and the infarct and scar tissue volumes were measured. Results: Aged rats showed more severe behavioral impairments and diminished functional recovery compared to young rats. Most infarcted animals had disturbances of sensorimotor function, with recovery beginning later, progressing more slowly, and reaching a lower functional endpoint in aged animals. However, the enriched environment significantly improved the rate and extent of recovery in aged animals. Correlation analysis revealed that the beneficial effect of the enriched environment on recovery, both in young and aged rats, correlated highly with a reduction in infarct size, in the number of proliferating astrocytes, and in the volume of the glial scar. Conclusions: These results suggest that temporally modulating astrocytic proliferation and the ensuing scar formation might be a fruitful approach to improving functional recovery after stroke in aged rats. Show more

Keywords: Aging, environment, ischemia, rat, recovery, scar, stroke

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 5-6, pp. 467-484, 2007

Authors: Dey, Nicholas D. | Boersen, Angela J. | Myers, Rebecca A. | York, Lynae R. | Bombard, Matthew C. | Lu, Ming | Sandstrom, Michael I. | Hulce, Verne D. | Lescaudron, Laurent | Dunbar, Gary L.

Article Type: Research Article

Abstract: Purpose: The purpose of this study was to test the potential therapeutic effects of the substituted pyrimidine, KP544, which has been shown to amplify the effects of nerve growth factor in vitro, on motor deficits in the R6/2 transgenic mouse model of Huntington's disease (HD). Methods: Young, female R6/2 mice were given daily oral intubation of either 10 mg/kg KP544 or vehicle (0.5% methylcellulose) at 6 weeks of age and tested from postnatal weeks …8 through 12 on a battery of motor tasks, including assessments of clasping (drawing of the limbs to the torso when suspended by the tail), motor coordination on the rotarod, and spontaneous motor activity in the open-field. Following testing, the mice were sacrificed and the brains were sectioned and stained with cresyl violet for histological examination. Results: KP544 treatment decreased balance deficits on the rotarod task, reduced clasping, delayed the onset of hypoactivity, and reduced enlargement of the lateral ventricles in R6/2 mice. Conclusion: These results suggest that KP544 can reduce motor deficits and anatomical alterations in R6/2 mice. Further research into the use of KP544 as a potential pharmacotherapy HD is warranted. Show more

Keywords: Rotarod, clasping, spontaneous motor activity, nerve growth factor amplifier

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 5-6, pp. 485-492, 2007

Authors: Breitenstein, Caterina | Zwitserlood, Pienie | de Vries, Meinou H. | Feldhues, Christiane | Knecht, Stefan | Dobel, Christian

Article Type: Research Article

Abstract: Purpose: The best predictor of successful language therapy in both the acute and chronic stages after stroke is the treatment intensity, i.e., number of hours trained per week. Associative learning should be particularly suited for intense training because it places low demands on (executive) cognitive functions. It is as of yet unresolved, however, whether associative training is a valid language learning approach. It could merely produce superficial associations of acoustic-visual information, which remain outside …lexical and conceptual networks. Methods: We here examined if five days of associative training in a miniature vocabulary are sufficient for an integration of novel words into the learner's mental lexicon. Twelve healthy subjects were trained 20 min daily for five consecutive days simply by frequent couplings of object pictures with novel words. Results: Correct responses for couplings of novel words and object names increased from a chance level of 50 percent on day 1 to > 90 percent accuracy on day 5. Prior to and immediately after the vocabulary training, a cross-modal semantic priming test was administered to determine the degree of lexical integration of the novel words into the language system already in situ. Conclusions: Results show that learned novel words had acquired semantic characteristics, which were comparable to words of subjects' native language acquired over a lifetime. Thus, comprehensive integration of the novel words into existing conceptual and lexical networks occurred after just five days of training. This lays the foundation for probing associative training approaches in aphasia therapy, with the hope of increasing therapy efficiency. Show more

Keywords: Language acquisition, aphasia therapy, semantic priming, anomia

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 5-6, pp. 493-500, 2007

Authors: Müller, Katharina | Bütefisch, C.M. | Seitz, Rüdiger J. | Hömberg, Volker

Article Type: Research Article

Abstract: Purpose: In a multiple baseline design, we tested the hypothesis that imagery of finger movements is a specific strategy to improve hand function. Methods: The effect of mental training of sequential finger movements (n=6) on hand function was compared to the repetitive execution of the same movements (n=6) and conventional physical therapy (n=5) in 17 patients after their first hemiparetic stroke. The behavioral outcome measures consisted of peak force of the pinch grip using …a force transducer and manipulation functions of the upper extremity (Jebsen-test). In addition, activities of daily living (Barthel Index) were aquired to describe the population. Results: Mental training resulted in an increase in the peak force of the pinch grip and generalized in a better functionality of the upper extremity (Jebsen-test). This effect was similar to the repetitive execution of the movements and superior to conventional physiotherapy. Conclusions: Our results suggest that the control of finger movements benefits from mental training of sequential finger movements and, thus, may be employed as a strategy in post-stroke rehabilitation. Show more

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 5-6, pp. 501-511, 2007

Authors: Pienaar, I.S. | Schallert, T. | Russell, V.A. | Kellaway, L.A. | Carr, J.A. | Daniels, W.M.U.

Article Type: Research Article

Abstract: Purpose: The infusion of 6-hydroxydopamine (6-OHDA) into the nigrostriatal pathway in rats is commonly used to produce an animal model of Parkinson's disease (PD). However, most studies use male adult animals only. The present study focused on possible gender differences in vulnerability to 6-OHDA during the early pubertal period when the effects exerted by gonadal steroid hormones are unpronounced. Methods: Young Sprague-Dawley rats, 35 days of age, were given a low vs. a higher dose …of 6-OHDA in the medial forebrain bundle (MFB). Control rats received equivalent saline infusions. At 14 days post-surgery the rats were evaluated for forelimb akinesia. Results: For the higher dose of 6-OHDA the female rats were less impaired than males in making adjustment steps in response to a weight shift and in a vibrissae-evoked forelimb placing test. Tyrosine hydroxylase (TH) immunoreactivity was significantly higher for the female rats. Conclusion: Early gender differences in cell survival factors and/or other promoters of neuroplasticity may have contributed to the beneficial outcome in the females. For example, NGF was found to be higher in the female rats following administration of DA neurotoxin. It is unclear whether gonadal steroids are involved, and if so, whether female hormones are protective or whether male hormones are prodegenerative. Determining the mechanisms for the improved outcome in the young female rats may lead to potential treatment strategies in PD. Show more

Keywords: Behaviour, dose-related effects, neuroprotection, Parkinson's disease, sexual dimorphism, 6-hydroxydopamine lesion

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 5-6, pp. 513-526, 2007

Authors: Edwards, D.J. | Mastaglia, F.L. | Byrnes, M.L. | Fregni, F. | Pascual-Leone, A. | Thickbroom, G.W.

Article Type: Research Article

Abstract: Corticomotor excitability is reduced during rhythmic passive movement compared to rest, but it is not known whether the mechanism is purely segmental or includes a supraspinal pathway. To determine how interruption of sensory projections at a supraspinal level affects corticomotor excitability during passive movement, we measured the amplitude of motor evoked potential (MEP) during 1 Hz cyclic index finger movements in a patient with a brainstem and thalamus lesion that resulted in a pure sensory stroke. …Measurements of MEP amplitude and proprioception were made 14 and 64 days post-stroke. In the first study, when subjective position sense was reduced for the index finger, MEP amplitude was significantly increased during passive movement compared to rest (4.6 ± 0.2 SEM mV vs. 4.0 ± 0.2 mV; p=0.0281). However in the second study, when position sense had returned to normal, MEP amplitude was significantly reduced during movement compared to rest (6.2 ± 0.3 mV vs. 6.6 ± 0.1 mV; p=0.0224). These observations provide evidence that supraspinal sensory pathways are involved in reducing corticomotor excitability during rhythmic passive movement. Show more

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 5-6, pp. 527-533, 2007

Authors: Si, Keyuan | Miotke, Jill A. | Meyer, Ronald L. | Wang, Ziren

Article Type: Research Article

Abstract: Purpose: Growing axons express a number of proteins associated with axonal growth which are thought to be critical for regeneration and sprouting. Whether these proteins are expressed during injury-induced axonal remodeling is tested in this paper. Methods: The posterior half of the adult goldfish tectum was removed leaving the anterior half intact. This causes optic fibers from nasal retina, which project to posterior tectum, to displace temporal fibers from the anterior remnant and form …a compressed retinotopic projection of the entire retina onto the anterior tectum. Immunohistochemistry using an antibody shown here to recognize growing and regenerating fibers in goldfish was used to monitor optic fibers. Results: As expected, surgery induced reactivity in the axotomized nasal axons peaking at 1 month which returned to normal at 2 months when compression was completed. Unexpectedly, axons from temporal retina showed no detectable reactivity even though they were induced to grow anteriorly by the invading nasal fibers. Conclusions: Extensive axonal remodeling and synaptic rearrangement can occur without reentering the growth state associated with axonal growth and regeneration. Show more

Keywords: GAP-43, immunohistochemistry, visual pathway, retina, tectum, optic nerve, nerve crush

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 5-6, pp. 535-547, 2007