Restorative Neurology and Neuroscience - Volume 39, issue 6

Authors: Sabel, Bernhard A. | Zhou, Wanshu | Huber, Frank | Schmidt, Florentina | Sabel, Kornelia | Gonschorek, Andreas | Bilc, Mirela

Article Type: Research Article

Abstract: Background: An effective treatment is needed for long-COVID patients which suffer from symptoms of vision and/or cognition impairment such as impaired attention, memory, language comprehension, or fatigue. Objective: Because COVID-19infection causes reduced blood flow which may cause neuronal inactivation, we explored if neuromodulation with non-invasive brain stimulation using microcurrent (NIBS), known to enhance blood flow and neuronal synchronization, can reduce these symptoms. Methods: Two female long-COVID patients were treated for 10–13 days with alternating current stimulation of the eyes and brain. While one patient (age 40) was infected with the SARS CoV-2 virus, the other (age …72) developed symptoms following AstraZeneca vaccination. Before and after therapy, cognition was assessed subjectively by interview and visual fields quantified using perimetry. One patient was also tested with a cognitive test battery and with a retinal dynamic vascular analyser (DVA), a surrogate marker of vascular dysregulation in the brain. Results: In both patients NIBS markedly improved cognition and partially reversed visual field loss within 3–4 days. Cognitive tests in one patient confirmed recovery of up to 40–60% in cognitive subfunctions with perimetry results showing stable and visual field recovery even during follow-up. DVA showed that NIBS reduced vascular dysregulation by normalizing vessel dynamics (dilation/constriction), with particularly noticeable changes in the peripheral veins and arteries. Conclusions: NIBS was effective in improving visual and cognitive deficits in two confirmed SARS-COV-2 patients. Because recovery of function was associated with restoration of vascular autoregulation, we propose that (i) hypometabolic, “silent” neurons are the likely biological cause of long-COVID associated visual and cognitive deficits, and (ii) reoxygenation of these “silent” neurons provides the basis for neural reactivation and neurological recovery. Controlled trials are now needed to confirm these observations. Show more

Keywords: Vision, cognition, restoration, recovery, corona, neuromodulation

DOI: 10.3233/RNN-211249

Citation: Restorative Neurology and Neuroscience, vol. 39, no. 6, pp. 393-408, 2021

Authors: Zhong, Yuhua | Fan, Jianzhong | Wang, Huijuan | He, Renhong

Article Type: Research Article

Abstract: Background: Interhemispheric asymmetry caused by brain lesions is an adverse factor in the recovery of patients with neurological deficits. Repetitive transcranial magnetic stimulation (rTMS) has been shown to modulate cortical oscillation and proposed as an approach to rebalance the symmetry, which has not been documented well. Objective: In this study, we investigated the influence of repetitive transcranial magnetic stimulation (rTMS) on EEG power in patients with unilateral brain lesions by simultaneously stimulating both brain hemispheres and to elucidate asymmetrical changes in rTMS-induced neurophysiological activity. Methods: Fourteen patients with unilateral brain lesions were treated with one active …and one sham session of 10 Hz rTMS over the vertex (Cz position). Resting-state EEGs were recorded before and immediately after rTMS. The brain symmetry index (BSI), calculated from a fast Fourier transform, was employed to quantify the power asymmetry in both hemispheres and paired channels over the entire range and five frequency bands (delta, theta, alpha, beta and gamma bands). Results: Comparison between active and sham sessions demonstrated rTMS-induced EEG after-effects. rTMS in the active session significantly reduced the BSI in patients with unilateral brain lesions over the entire frequency range (t  = 2.767, P  = 0.016). Among the five frequency bands, rTMS only induced a noticeable decrease in the BSI in the delta band (t  = 2.254, P  = 0.042). Furthermore, analysis of different brain regions showed that significant changes in the BSI of the alpha band were only demonstrated in the posterior parietal lobe. In addition, EEG topographic mapping showed a decreased power of delta oscillations in the ipsilesional hemisphere, whereas distinct cortical oscillations were observed in the alpha band around the parietal-occipital lobe in the contralesional hemisphere. Conclusions: When both brain hemispheres were simultaneously activated, rTMS decreased interhemispheric asymmetry primarily via reducing the delta band in the lesioned hemisphere. Show more

Keywords: Brain symmetry index, oscillation, repetitive transcranial magnetic stimulation, resting-state EEG, unilateral brain lesions

DOI: 10.3233/RNN-211172

Citation: Restorative Neurology and Neuroscience, vol. 39, no. 6, pp. 409-418, 2021

Authors: Chen, Qing-Mei | Yao, Fei-Rong | Sun, Hai-Wei | Chen, Zhi-Guo | Ke, Jun | Liao, Juan | Cai, Xiu-Ying | Yu, Li-Qiang | Wu, Zhen-Yan | Wang, Zhi | Pan, Xi | Liu, Hao-Yu | Li, Li | Zhang, Quan-Quan | Ling, Wei-Hua | Fang, Qi

Article Type: Research Article

Abstract: Background: The combination of inhibitory and facilitatory repetitive transcranial magnetic stimulation (rTMS) can improve motor function of stroke patients with undefined mechanism. It has been demonstrated that rTMS exhibits a neuro-modulatory effect by regulating the major inhibitory neurotransmitter γ-aminobutyric acid (GABA) in other diseases. Objectives: To evaluate the effect of combined inhibitory and facilitatory rTMS on GABA in the primary motor cortex (M1) for treating motor dysfunction after acute ischemic stroke. Methods: 44 ischemic stroke patients with motor dysfunction were randomly divided into two groups. The treatment group was stimulated with 10 Hz rTMS at the ipsilesional …M1 and 1 Hz rTMS at the contralesional M1. The sham group received bilateral sham stimulation at the motor cortices. The GABA level in the bilateral M1 was measured by proton magnetic resonance spectroscopy (1 H-MRS) at 24 hours before and after rTMS stimulation. Motor function was measured using the Fugl-Meyer Assessment (FMA). The clinical assessments were performed before and after rTMS and after 3 months. Results: The treatment group exhibited a greater improvement in motor function 24 hours after rTMS compared to the sham group. The increased improvement in motor function lasted for at least 3 months after treatment. Following 4 weeks of rTMS, the GABA level in the ipsilesional M1 of the treatment group was significantly decreased compared to the sham group. Furthermore, the change of FMA score for motor function was negatively correlated to the change of the GABA:Cr ratio. Finally, the effect of rTMS on motor function outcome was partially mediated by GABA level change in response to the treatment (27.7%). Conclusions: Combining inhibitory and facilitatory rTMS can decrease the GABA level in M1, which is correlated to the improvement of motor function. Thus, the GABA level in M1 may be a potential biomarker for treatment strategy decisions regarding rTMS neuromodulatory interventions. Show more

Keywords: Facilitatory repetitive magnetic stimulation, inhibitory repetitive transcranial magnetic stimulation, motor function, stroke, GABA, magnetic resonance spectroscopy, mediating effects, rehabilitation

DOI: 10.3233/RNN-211195

Citation: Restorative Neurology and Neuroscience, vol. 39, no. 6, pp. 419-434, 2021

Authors: Fonte, Cristina | Varalta, Valentina | Rocco, Arianna | Munari, Daniele | Filippetti, Mirko | Evangelista, Elisa | Modenese, Angela | Smania, Nicola | Picelli, Alessandro

Article Type: Research Article

Abstract: Background: Upper limb motor deficits in patients with severe stroke often remain unresolved over time. Combining transcranial Direct Current Stimulation with robotic therapy is an innovative neurorehabilitation approach that holds promise to improve upper limb impairment after stroke. Objective: To investigate the effects of robotic training in combination with transcranial Direct Current Stimulation for treating poststroke upper limb impairment. Methods: PubMed, MEDLINE, Cochrane Library, and EMBASE electronic databases were searched using keywords, MeSH terms, and strings: “Stroke”[MeSH] AND (“Upper Extremity”[MeSH] OR “upper limb”) AND (“Transcranial Direct Current Stimulation” [MeSH] OR “tDCS”) AND (“robotics” OR “robotic therapy”). …Full-text articles published in English up to October 2020 were included. Each was rated for quality according to the Physiotherapy Database (PEDro) score: eight out of eleven scored more than 8 points; their results were considered reliable for this review. Results: Of the total of 171 publications retrieved, 11 met the inclusion criteria. The results of studies that examined the same outcome measures were pooled to draw conclusions on the effectiveness of transcranial Direct Current Stimulation and robot-assisted training in corticomotor excitability, upper limb kinematics, muscle strength and tone, function, disability, and quality of life after stroke. Conclusions: To date, there is insufficient evidence to support the hypothesis that transcranial Direct Current Stimulation enhances the effects of robot-assisted arm training in poststroke patients. Further studies with more accurate, comparable and standardized methodology are needed in order to better define the effects of robotic training in combination with transcranial Direct Current Stimulation on poststroke upper limb impairment. Therefore, given the scarce resources available to rehabilitation researches, other, more promising approaches should be given attention. Show more

Keywords: Brain stimulation, recovery of function, rehabilitation, robotics

DOI: 10.3233/RNN-211218

Citation: Restorative Neurology and Neuroscience, vol. 39, no. 6, pp. 435-446, 2021

Authors: Houben, Milan | Chettouf, Sabrina | Van Der Werf, Ysbrand D. | Stins, John

Article Type: Research Article

Abstract: Background: Unilateral neglect (UN) is a common and disabling disorder after stroke. UN is a strong and negative predictor of functional rehabilitative outcome. Non-invasive brain stimulation, such as theta-burst transcranial magnetic stimulation (TBS), is a promising rehabilitation technique for treating stroke-induced UN. Objective: To systematically review the available literature, researching whether TBS of the contra-lesional hemisphere is more effective than standard rehabilitation in improving symptoms of UN in patients with right hemisphere stroke. Review methods: A systematic review was conducted to retrieve randomized controlled trials (RCTs) that were relevant to the objective of this review. PubMed, …Ovid and Cochrane Library electronic databases were comprehensively searched from inception up to February 2021. Of the included studies, methodological quality was assessed using the PEDro scale, whereafter a best evidence synthesis (BES) was conducted to summarize the results. Results: Nine RCTs investigating the effects of TBS on stroke-induced UN symptoms were included in this review. Seven studies assessing continuous TBS (cTBS) found significantly greater amelioration of UN symptoms in the TBS intervention group when compared to the control group; one study assessing cTBS found no such significant difference. One study assessing intermittent TBS (iTBS) found significant between-group differences in favor of the intervention. The BES yielded strong evidence in favor of cTBS, and limited evidence in favor of iTBS. Conclusions: The included studies in the present review allow the conclusion that TBS can have favorable effects on UN recovery in stroke patients. Its clinical use is recommended in conjunction with cognitive rehabilitation and occupational or physical rehabilitation as needed. However, many aspects for optimal usage of TBS therapy in clinical settings, such as exact TBS protocols, number of sessions, and treatment duration, are not clear. Show more

Keywords: Transcranial magnetic stimulation, theta-burst stimulation, unilateral neglect, stroke, systematic review

DOI: 10.3233/RNN-211228

Citation: Restorative Neurology and Neuroscience, vol. 39, no. 6, pp. 447-465, 2021