Restorative Neurology and Neuroscience - Volume 32, issue 3

Authors: Prokosch, Verena | Thanos, Solon

Article Type: Research Article

Abstract: Purpose: Nonarteriitic anterior ischemic optic neuropathy (NAION) is a leading cause of sudden loss of vision, which particularly affects individuals older than 50 years. Up to now there is no treatment that is effective at reversing or limiting the course of this disease. To study the short- and long-term effects of fluocortolone (FC) on the visual outcome of patients with acute NAION compared to standard treatment with pentoxifylline (PFX). Methods: A prospective, quasirandomized intervention trial was conducted involving 60 patients with acute-onset NAION. Patients in the comparison (PFX) group (n = 30) received PFX intravenously and per os for 7 …days and then per os for a further 6 months, which is a standard treatment. Patients in the intervention (PFX + FC) group (n = 30) received the standard treatment plus 1 mg/kg FC for 5 days, with a subsequent stepwise dose reduction over time. As a primary outcome measure, the best corrected visual acuity (BCVA) was determined at the initial baseline consultation (i.e., before treatment), and at 3 days and 6 months after therapy onset. Visual field (VF) was analyzed using standard automated perimetry at the initial baseline examination and at 6 month after therapy onset. Changes in BCVA and visual field in the PFX and PFX + FC groups were compared and analyzed statistically. Results: Treatment with FC resulted in a significant improvement in BCVA. Patients receiving FC in acute NAION were more likely to experience improvement and less likely to have worsened visual acuity (mean BCVA scores: at baseline, 0.22; after 3 days and 6 months of treatment, 0.33 and 0.43, respectively) than PFX patients (mean BCVA scores: at baseline, 0.33; after 3 days and 6 months of treatment, 0.33 and 0.28, respectively; p < 0.002 and 0.001). The beneficial effect was even more marked 6 months after therapy onset. Remarkably, patients with a baseline BCVA score of >=0.05 profited significantly by FC treatment (p < 0.006 and 0.001), whereas those with a baseline BCVA score of <0.05 did not (p < 0.4). PFX did not improve BCVA. However, VF did not show any significant improvement due to FC therapy. Conclusion: This is the first prospective randomized intervention trial that demonstrates the distinctive beneficial effects of FC in terms of the visual outcome of patients with NAION compared to standard treatment with only PFX. FC significantly improves both short- and long-term visual acuity in patients with moderate BCVA impairment due to recent onset of NAION, while VF did not show any significant improvement; however, PFX did neither enhance BCVA nor VF. Administration of FC should be seriously considered for the treatment of NAION whenever there are no contraindications. Show more

Keywords: Nonarteriitic anterior ischemic optic neuropathy, fluocortolone, visual acuity, pentoxifylline, short- and long-term visual outcome, visual acuity

DOI: 10.3233/RNN-120292

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 3, pp. 381-389, 2014

Authors: Drummond, Eleanor S. | Rodger, Jennifer | Penrose, Marissa | Robertson, Donald | Hu, Ying | Harvey, Alan R.

Article Type: Research Article

Abstract: Purpose: In adult rats, intravitreal injections of the Rho-GTPase inhibitor C3 transferase (BA-210), or a cocktail of recombinant ciliary neurotrophic factor (CNTF) and a cyclic AMP analogue (CPTcAMP), increase retinal ganglion cell (RGC) survival and axonal regeneration. Here we examined whether these treatments also affect the dendritic architecture of regrowing RGCs. Methods: In Fischer F344 rats, one optic nerve was cut and an autologous peripheral nerve graft was sutured onto it. Rats then received intravitreal injections (4 μl) of saline, BA-210 or CNTF + CPTcAMP four and eleven days after the PN graft surgery. After 5 weeks, regenerating RGCs were …retrogradely labelled with fluorogold (FG) and in living wholemounts the dendritic trees of FG labelled RGCs were visualised by intracellular injection of 2% Lucifer Yellow. Results: Injection of BA-210 or CNTF + CPTcAMP resulted in significantly more regenerating RGCs with abnormal dendritic morphologies, including abnormally long looping processes. Compared to saline-injected regenerating controls, RGCs in BA-210 injected eyes had significantly smaller dendritic field areas and sparser dendrites, while in CNTF + CPTcAMP injected eyes there was increased branching of more distal dendrites. Conclusions: While both intraocular treatments enhance RGC axonal regrowth, they also induce significant changes in RGC dendritic morphology. It remains to be determined if such changes alter the function of the regenerating neuronal population. Show more

Keywords: Optic nerve injury, retina, regeneration, C3 transferase, peripheral nerve graft

DOI: 10.3233/RNN-130360

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 3, pp. 391-402, 2014

Authors: Laczó, Bence | Antal, Andrea | Rothkegel, Holger | Paulus, Walter

Article Type: Research Article

Abstract: Purpose: Transcranial random noise stimulation (tRNS) can increase the excitability of hand area of the primary motor cortex (M1). The aim of this study was to compare the efficacy of tRNS and transcranial direct current stimulation (tDCS) on the leg motor cortex. Method: Ten healthy subjects received anodal, cathodal tDCS, tRNS and sham stimulation for 10 min using 2 mA intensity during separate experimental sessions. Single pulse transcranial magnetic stimulation (TMS) induced motor evoked potential (MEP) measurements were used to assess motor cortical excitability changes after the stimulation. Results: Similar to the hand area, we found that both tRNS and …anodal tDCS induced an increase of the amplitude of the MEPs. Anodal tDCS induced a constant gradual increase of corticospinal excitability until 60 min post-stimulation, whereas the effect of tRNS was immediate with a duration of 40 min following stimulation. The cathodal tDCS induced decrease in MEP amplitude did not reach statistical significance. Conclusion: Our results suggest that although the leg area has a deeper position in the cortex compared to the hand area, it can be reached by weak transcranial currents. Both anodal tDCS and tRNS had comparable effect on cortical excitability. Show more

Keywords: tRNS, tDCS, leg motor cortex, TMS, human

DOI: 10.3233/RNN-130367

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 3, pp. 403-410, 2014

Authors: Walton, Courtney C. | Shine, James M. | Mowszowski, Loren | Naismith, Sharon L. | Lewis, Simon J. G.

Article Type: Research Article

Abstract: Freezing of gait (FOG) is a complex motor symptom of Parkinson's disease that manifests as an inability to generate effective gait, leading to a significant falls risk and a severe impact on quality of life. Research into effective treatment options has provided relatively limited benefits and is often hindered by substantial limitations. In this article, current treatment and research options are briefly discussed and a proposal for the further exploration of non-invasive therapeutic approaches is given. Recent advances in the literature continue to identify a pattern of selective executive dysfunction in patients with freezing of gait and such findings highlight …a possible common underlying pathophysiology. Therefore, cognitive training is of particular interest as it may be able to improve executive processes thus reducing the manifestation of FOG. This article focuses on the existing evidence for such intervention strategies and proposes that targeted cognitive training may offer a novel treatment option for FOG that is worthy of an increased research focus. Show more

Keywords: Freezing of gait, Parkinson's disease, cognitive training, executive function, neurorehabilitation

DOI: 10.3233/RNN-130370

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 3, pp. 411-422, 2014

Authors: Saiote, Catarina | Goldschmidt, Thomas | Timäus, Charles | Steenwijk, Martijn D. | Opitz, Alexander | Antal, Andrea | Paulus, Walter | Nitsche, Michael A.

Article Type: Research Article

Abstract: Purpose: Fatigue is a frequent and difficult to treat symptom affecting patients with multiple sclerosis (MS) with a profound negative impact on quality of life. Fatigue has been associated with functional and structural abnormalities of the frontal cortex, including frontal hypo-activation. The aim of this exploratory study was to assess whether fatigue symptoms can be reduced by excitability-enhancing anodal transcranial direct current stimulation (tDCS). Methods: In this sham-controlled, double-blind intervention study, tDCS was applied over the left prefrontal cortex of MS patients with fatigue for five consecutive days. Symptoms were tracked for 1 month via questionnaires. Lesion load at baseline …was calculated for each patient and correlated with fatigue levels and responsiveness to stimulation. Results: In the whole group analysis the scores of the fatigue scales were not altered by tDCS. However, in an exploratory analysis we found a correlation between response to the stimulation regarding subjectively perceived fatigue and lesion load in the left frontal cortex: patients responding positively to anodal tDCS had higher lesion load, compared to non-responding patients. Conclusion: We conclude that in patient subgroups discernible by specific morphological alterations, tDCS may be a tool for MS fatigue management. Show more

Keywords: Multiple sclerosis, fatigue, tDCS, lesion load, MRI

DOI: 10.3233/RNN-130372

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 3, pp. 423-436, 2014

Authors: Lin, Yu-Ching | Kao, Chia-Hong | Cheng, Yu-Kai | Chen, Jia-Jin J. | Yao, Chun-Hsu | Chen, Yueh-Sheng

Article Type: Research Article

Abstract: Purpose: To study if electrical stimulation (ES) can be a useful tool to improve functional recovery after neuronal injury in the peripheral nervous system. Methods: We studied the effects of 2 Hz of percutaneous ES at different intensities of 1, 10 and 20 mA on peripheral nerve regeneration in rats with diabetes induced by streptozotocin. Non-stimulated diabetic rats were used as the sham-controls. A10-mm gap was made in the rat sciatic nerve by suturing the stumps into silicone rubber tubes and stimulation was carried out every other day for 3 weeks starting 1 week after surgery. Results: After 4 weeks …of recovery, the diabetic rats showed that ES of 1 mA or above could increase the cutaneous blood flow in their ipsilateral hindpaw to the injury. ES of 10 mA could improve the amplitude and the area of evoked muscle action potentials with faster target muscle reinnervation. ES of 10 mA could also ameliorate the calcitonin gene-related peptide expression in lamina I-II regions in the dorsal horn ipsilateral to the injury and the number of macrophages in the diabetic distal sciatic nerve. The impaired growth and maturation of regenerating axons in diabetic rat could be improved by ES of 10 mA or above. Conclusions: All these results lead to the conclusion that ES of 10 mA or above might be necessary to improve regeneration after a dissect lesion of the sciatic nerve in the diabetic rat. Show more

Keywords: Electrical stimulation, peripheral nerve regeneration, diabetes, current intensity

DOI: 10.3233/RNN-130381

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 3, pp. 437-446, 2014