Restorative Neurology and Neuroscience - Volume 38, issue 4

Authors: Güntensperger, Dominik | Kleinjung, Tobias | Neff, Patrick | Thüring, Christian | Meyer, Martin

Article Type: Research Article

Abstract: Background: Alpha/delta neurofeedback has been shown to be a potential treatment option for chronic subjective tinnitus. Traditional neurofeedback approaches working with a handful of surface electrodes have been criticized, however, due to their low spatial specificity. Objective: The purpose of this study was to evaluate an innovative tomographic neurofeedback protocol that combines neural activity measured across the whole scalp with sLORETA source estimation. Methods: Forty-eight tinnitus patients participated in 15 neurofeedback training sessions as well as extensive pre, post, and follow-up testing. Patients were randomly assigned to either a tomographic (TONF) or a traditional electrode-based neurofeedback …(NTNF) group. Main outcome measures of this study were defined as tinnitus-related distress measured with the Tinnitus Handicap Inventory (THI) and Tinnitus Questionnaire (TQ), tinnitus loudness, and resting-state EEG activity in trained frequency bands. Results: For both groups a significant reduction of tinnitus-related distress and tinnitus loudness was found. While distress changes remained persistent irrespective of group, loudness levels returned to baseline in the follow-up period. No significant between-group differences between the 2 neurofeedback applications (TONF vs. NTNF) were found, which suggests a similar contribution to symptom improvement. The trained alpha/delta ratio increased significantly over the course of the training and remained stable in the follow-up period. This effect was found irrespective of group on both surface and source levels with no meaningful differences between the 2 groups. Conclusions: Our study shows that a tomographic alpha/delta protocol should be considered a promising addition to tinnitus treatment but that more individually specific neurofeedback protocols should be developed. Show more

Keywords: Tinnitus, neurofeedback, EEG, alpha, delta, tomographic, sLORETA

DOI: 10.3233/RNN-200992

Citation: Restorative Neurology and Neuroscience, vol. 38, no. 4, pp. 283-299, 2020

Authors: Page, Stephen J. | Kasner, Scott E. | Bockbrader, Marcia | Goldstein, Mark | Finklestein, Seth P. | Ning, MingMing | El-Feky, Waleed H. | Wilson, Christina A. | Roberts, Holly | on behalf of all of the investigators involved in the MILESTONE study

Article Type: Research Article

Abstract: Background: Stroke-induced ischemia affects both cortex and underlying white matter. Dalfampridine extended release tablets (D-ER) enhance action potential conduction in demyelinated axons, which may positively affect post-stroke recovery. Objective: Based on promising preliminary data, we compared efficacy of D-ER administered at 7.5 mg or 10 mg with placebo on post-stroke ambulation. Primary study outcome (response) was a ≥20% increase on the 2-minute walk test (2 MinWT) at 12 weeks after first drug administration. Methods: This was a multicenter, randomized, placebo-controlled, 3-arm, parallel-group, safety and efficacy trial. After obtaining baseline measures of 2 MinWT, Walk-12, and Timed Up and Go, subjects …entered a 2-week, single-blind placebo run-in period and were randomized 1:1:1 to receive 7.5 mg D-ER, 10 mg D-ER, or placebo, dosed twice-daily for 12 weeks. Follow-up evaluations occurred at weeks 14 and 16 when subjects were off study drug. Results: The study was terminated early with 377 of planned 540 patients enrolled, due to no treatment effect. At week 12, mean increase in distances walked in 2 minutes were similar among the 3 study groups (14.9±40.0 feet; 19.4±39.6 feet; and 20.4±38.3 feet for placebo, 7.5 mg D-ER, and 10 mg D-ER, respectively). The proportion of subjects who showed ≥20% improvement on 2 MinWT at week 12 was 13.5%, 14.0%, and 19.0%, for placebo, 7.5 mg D-ER, and 10 mg D-ER, respectively; these were nonsignificant changes from baseline for all groups. Conclusions: D-ER at either a 7.5-mg or 10-mg dose did not significantly increase performance on the 2 MinWT in stroke survivors with gait impairment, although this study was terminated early before full enrollment. (Clinical Trial # NCT02271217). Show more

Keywords: stroke, lower extremity, rehabilitation, ambulation, hemiplegia

DOI: 10.3233/RNN-201009

Citation: Restorative Neurology and Neuroscience, vol. 38, no. 4, pp. 301-309, 2020

Authors: Zhu, Jiaying | Ma, Mengmeng | Fang, Jinghuan | Bao, Jiajia | Dong, Shuju | Chen, Ning | Guo, Yijia | He, Li

Article Type: Research Article

Abstract: Background: Statin therapy has been shown to be effective in the prevention of ischemic stroke. In addition, recent studies have suggested that prior statin therapy could lower the initial stroke severity and improve stroke functional outcomes in the event of stroke. It was speculated that prestroke statin use may enhance collateral circulation and result in favorable functional outcomes. Objective: The aim of the study was to investigate the association of prestroke statin use with leptomeningeal collaterals and to determine the association of prestroke statin use with stroke severity and functional outcome in acute ischemic stroke patients. …Methods: We prospectively and consecutively enrolled 239 acute ischemic stroke patients with acute infarction due to occlusion of the middle cerebral artery within 24 h in the neurology department of West China Hospital from May 2011 to April 2017. Computed tomographic angiography (CTA) imaging was performed for all patients to detect middle cerebral artery thrombus; regional leptomeningeal collateral score (rLMCS) was used to assess the degree of collateral circulation; the National Institutes of Health Stroke Scale (NIHSS) was used to measure stroke severity at admission; the modified Rankin scale (mRS) was used to measure outcome at 90 days; and premorbid medications were recorded. Univariate and multivariate analyses were performed. Results: Overall, 239 patients met the inclusion criteria. Fifty-four patients used statins, and 185 did not use statins before stroke onset. Prestroke statin use was independently associated with good collateral circulation (rLMCS > 10) (odds ratio [OR], 4.786; 95% confidence interval [CI], 1.195–19.171; P  = 0.027). Prestroke statin use was not independently associated with lower stroke severity (NIHSS score≤14) (OR, 1.955; 95% CI, 0.657–5.816; p  = 0.228), but prestroke statin use was independently associated with favorable outcome (mRS score≤2) (OR, 3.868; 95% CI, 1.325–11.289; P  = 0.013). Conclusions: Our findings suggest that prestroke statin use was associated with good leptomeningeal collaterals and clinical outcomes in acute ischemic stroke (AIS) patients presenting with occlusion of the middle cerebral artery. However, clinical studies should be conducted to verify this claim. Show more

Keywords: Statin, acute ischemic stroke, collateral circulation, outcome, stroke subtypes, infarct position

DOI: 10.3233/RNN-201012

Citation: Restorative Neurology and Neuroscience, vol. 38, no. 4, pp. 311-321, 2020

Authors: Gao, Yuhua | Ma, Liping | Han, Tao | Wang, Meng | Zhang, Dongmei | Wang, Yana

Article Type: Research Article

Abstract: This article has been retracted, and the online PDF has been watermarked “RETRACTED”. A retraction notice is available at DOI: 10.3233/RNN-239001 .

DOI: 10.3233/RNN-201022

Citation: Restorative Neurology and Neuroscience, vol. 38, no. 4, pp. 323-331, 2020

Authors: Tramontano, Marco | Morone, Giovanni | De Angelis, Sara | Casagrande Conti, Laura | Galeoto, Giovanni | Grasso, Maria Grazia

Article Type: Research Article

Abstract: Background: Sensor-based technological therapy devices may be good candidates for neuromotor rehabilitation of people with Multiple Sclerosis (MS), especially for treating upper extremities function limitations. The sensor-based device rehabilitation is characterized by interactive therapy games with audio-visual feedback that allows training the movement of shoulders, elbows, and wrist, measuring the strength and the active range of motion of upper limb, registering data in an electronic database to quantitatively monitoring measures and therapy progress. Objective: This study aimed to investigate the effects of sensor-based motor rehabilitation in add-on to the conventional neurorehabilitation, on increasing the upper limb functions of …patients with MS. Methods: Thirty patients were enrolled in the study and randomly assigned to the experimental group and the control group. The training consisting of twelve sessions of upper limb training was compared with twelve sessions of upper limb sensory-motor training, without robotic support. Both rehabilitation programs were performed for 40 minutes three times a week, for 4 weeks, in addition to conventional therapy. All patients were evaluated at the baseline (T0) and after 4 weeks of training (T1). Results: The within-subject analysis showed a statistically significant improvement in both groups, in the Modified Barthel Index and in the Rivermead Mobility Index scores and a significant improvement in Multiple Sclerosis Quality of Life-54 in the experimental. The analysis of effectiveness revealed that, compared with baseline (T0), the improvement percentage in all clinical scale scores was greater in the experimental group than the control group. Conclusions: Proposed training provides an intensive and functional-oriented rehabilitation that objectively evaluates achieved progress through exercises. Therefore, it can represent a good complementary strategy for hand rehabilitation in MS patients. Show more

Keywords: Multiple sclerosis, sensor-based therapy, hand rehabilitation, NCT04367285

DOI: 10.3233/RNN-201033

Citation: Restorative Neurology and Neuroscience, vol. 38, no. 4, pp. 333-341, 2020

Authors: Turski, Waldemar A. | Wnorowski, Artur | Turski, Gabrielle N. | Turski, Christopher A. | Turski, Lechoslaw

Article Type: Research Article

Abstract: Covid-19 is the acute illness caused by SARS-CoV-2 with initial clinical symptoms such as cough, fever, malaise, headache, and anosmia. After entry into cells, corona viruses (CoV) activate aryl hydrocarbon receptors (AhRs) by an indoleamine 2,3-dioxygenase (IDO1)-independent mechanism, bypassing the IDO1-kynurenine-AhR pathway. The IDO1-kynurenine-AhR signaling pathway is used by multiple viral, microbial and parasitic pathogens to activate AhRs and to establish infections. AhRs enhance their own activity through an IDO1-AhR-IDO1 positive feedback loop prolonging activation induced by pathogens. Direct activation of AhRs by CoV induces immediate and simultaneous up-regulation of diverse AhR-dependent downstream effectors, and this, in turn, results in …a “Systemic AhR Activation Syndrome” (SAAS) consisting of inflammation, thromboembolism, and fibrosis, culminating in multiple organ injuries, and death. Activation of AhRs by CoV may lead to diverse sets of phenotypic disease pictures depending on time after infection, overall state of health, hormonal balance, age, gender, comorbidities, but also diet and environmental factors modulating AhRs. We hypothesize that elimination of factors known to up-regulate AhRs, or implementation of measures known to down-regulate AhRs, should decrease severity of infection. Although therapies selectively down-regulating both AhR and IDO1 are currently lacking, medications in clinical use such as dexamethasone may down-regulate both AhR and IDO1 genes, as calcitriol/vitamin D3 may down-regulate the AhR gene, and tocopherol/vitamin E may down-regulate the IDO1 gene. Supplementation of calcitriol should therefore be subjected to epidemiological studies and tested in prospective trials for prevention of CoV infections, as should tocopherol, whereas dexamethasone could be tried in interventional trials. Because lack of physical exercise activates AhRs via the IDO1-kynurenine-AhR signaling pathway increasing risk of infection, physical exercise should be encouraged during quarantines and stay-at-home orders during pandemic outbreaks. Understanding which factors affect gene expression of both AhR and IDO1 may help in designing therapies to prevent and treat humans suffering from Covid-19. Show more

Keywords: Corona virus, SARS-CoV-2, Covid-19, aryl hydrocarbon receptor, indoleamine 2,3-dioxygenase, systemic AhR activation syndrome (SAAS), inflammation, thromboembolism, fibrosis, multiple organ injury, brain injury, respiratory failure, dexamethasone, vitamin D, vitamin E, physical exercise

DOI: 10.3233/RNN-201042

Citation: Restorative Neurology and Neuroscience, vol. 38, no. 4, pp. 343-354, 2020