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Neurological Rehabilitation: Repair Mechanisms, Plasticity, and Connectomes

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Clinical Neurology".

Deadline for manuscript submissions: closed (20 December 2025) | Viewed by 3545

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Special Issue Editors

Prof. Dr. Thomas Mokrusch

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Guest Editor

German Brain Council, University of Erlangen-Nürnberg, Friedrichstr. 88, 10117 Berlin, Germany
Interests: neurorehabilitation; mechanical ventilation; brain

Prof. Dr. Frank Kirchhoff

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Guest Editor

1. Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of Saarland, 66421 Homburg, Germany
2. Center for Gender-specific Biology and Medicine (CGBM), University of Saarland, 66421 Homburg, Germany
Interests: neuroscience; synaptic transmission; astrocytes; neuroglia; molecular and cellular mechanisms of neuron-glia interaction in the central nervous system

Special Issue Information

Dear Colleagues,

"There is no health without brain health" is the guiding principle behind neurological rehabilitation (which, of course, includes not only diseases of the CNS but also those of the peripheral nervous system). Currently, 15 percent of people worldwide suffer from a neurological condition, and this results in enormous costs, including more than EUR 800 billion annually in Europe alone. Research in neurological rehabilitation is therefore crucial in enhancing future public health.

Neurological rehabilitation plays an important role in the overall structure of health care, as this period of treatment is usually the longest period during which patients receive and participate in restorative therapies.

This Special Issue will showcase therapeutic options currently available for neurological rehabilitation, what is known about their mechanisms of action, and what further developments can be expected in the future. This will be demonstrated using examples from vascular diseases, traumatic lesions, tumors, infectious and immunological diseases, and degenerative processes. In addition, this Special Issue will provide examples of how prevention and specific therapeutic measures can increase overall therapeutic success.

Prof. Dr. Thomas Mokrusch
Prof. Dr. Frank Kirchhoff
Guest Editors

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Keywords

neurorehabilitation
therapeutic approaches
repair mechanism
plasticity
neurology

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Published Papers (4 papers)

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Research

16 pages, 1121 KB

Open AccessFeature PaperArticle

Long-Term Outcome After Intensive Stroke Rehabilitation

by Marilena Geißler, Anika Müller, Thomas Brauner, Aline Weidlich and Imanuel Dzialowski

J. Clin. Med. 2026, 15(9), 3375; https://doi.org/10.3390/jcm15093375 - 28 Apr 2026

Viewed by 248

Abstract

Background: Ischemic stroke is the main cause of adult disability, with up to 25% of patients dying within the first year. In Germany, 4/10 patients receive in-hospital rehabilitation after acute stroke. Therefore, the aim of this study was to examine the association between modern neurological rehabilitation and the outcomes of patients with ischemic stroke. Methods: In our single-centre, prospective observational study, we included patients with ischemic stroke between March 2023–June 2025. Within the first year after discharge, we conducted telephone surveys, recording survival status, modified Rankin Scale score (mRS), and quality of life using EQ-5D-5L. Favourable outcomes were defined as mRS 0–2. Predictors of mortality and favourable outcomes after 12 months were calculated using multiple logistic regression. Results: We included 180 patients with ischemic stroke and complete one-year follow-up. Median age was 81 years, median Barthel Index at admission was 15 and median Charlson Comorbidity Index (CCI) was 4 points. Mortality during rehabilitation was 3.3% and 20.6% at 1 year. Only 10% achieved a favourable outcome after 12 months. Predictors of mortality were CCI (OR: 1.27 (1.01–1.61)) and discharge home (OR: 0.18 (0.06–0.48)). Predictors for favourable outcome were age (OR: 0.92 (0.87–0.97)), length of stay in rehabilitation (OR: 0.94 (0.91–0.97)) and weekly duration of neuropsychology (OR: 2.79 (1.27–6.66)). Conclusions: Multimorbid patients needing institutional care appear to have greater risk of death, while outcomes of younger patients, who needed less rehabilitation and had more consultation with neuropsychology, were associated with higher levels of independency after one year. Full article

(This article belongs to the Special Issue Neurological Rehabilitation: Repair Mechanisms, Plasticity, and Connectomes)

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12 pages, 7312 KB

Open AccessArticle

Symptom-Oriented, Connectome-Informed Deep Brain Stimulation for Asymmetric Dystonic Tremor: Unilateral Ventral Intermediate Nucleus (VIM) DBS Targeting a Tremor-Dominant Network

by Olga Mateo-Sierra, Javier Ricardo Pérez-Sánchez, Beatriz De la Casa-Fages, María Teresa Del Castillo, Pilar Fernández, Pascual Elvira, José Paz and Francisco Grandas

J. Clin. Med. 2026, 15(4), 1666; https://doi.org/10.3390/jcm15041666 - 23 Feb 2026

Viewed by 523

Abstract

Background: Deep brain stimulation (DBS) has traditionally followed diagnosis-driven, nucleus-centered targeting paradigms. Increasing evidence supports a circuit-based framework in which clinical outcomes depend on modulation of symptom-relevant networks rather than diagnostic labels alone. This approach is particularly relevant in mixed movement disorder phenotypes such as dystonic tremor, where the most disabling symptom may not align with the conventional surgical target. Methods: We report a clinically illustrative single case treated using a symptom-oriented, connectome-informed DBS strategy. Clinical phenotype, tremor severity, functional impairment, prior medical and botulinum toxin treatments, and longitudinal outcomes were systematically reviewed. DBS target selection prioritized the dominant, treatment-refractory symptom rather than the underlying dystonia diagnosis. Surgical planning incorporated high-resolution MRI with patient-specific thalamic segmentation using Brainlab Brain Elements^®, followed by postoperative lead localization and volume of tissue activated visualization with the SureTune™ platform. Results: A 54-year-old left-handed woman with long-standing cervical dystonia developed a severe, markedly asymmetric dystonic tremor predominantly affecting the left upper limb, resulting in profound functional disability. Instead of conventional bilateral globus pallidus internus DBS, unilateral right ventral intermediate nucleus (VIM) DBS was selected to engage tremor-related cerebellothalamic circuits. Rapid and marked improvement was observed, with tremor severity reduced to mild levels within 15 days after stimulation onset. At 6-month follow-up, overall tremor severity improved from 49 to 13 points on the Fahn–Tolosa–Marin Tremor Rating Scale, corresponding to a 73.5% reduction. This improvement was associated with restoration of legible handwriting, independent feeding and drinking, and recovery of bimanual fine motor function. Clinical benefit remained stable throughout follow-up, without stimulation-related adverse effects. Conclusions: This case illustrates the feasibility of a symptom-oriented, connectome-informed DBS strategy in selected patients with dystonic tremor. When symptom expression and network involvement are markedly asymmetric, selective unilateral modulation of the tremor-dominant circuit may achieve meaningful and durable functional improvement. Further studies are needed to assess the generalizability of this approach. Full article

(This article belongs to the Special Issue Neurological Rehabilitation: Repair Mechanisms, Plasticity, and Connectomes)

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24 pages, 2486 KB

Open AccessArticle

Immediate and Long-Term Effectiveness of a Therapeutic Exercise Protocol in Patients with Dementia

by Ferreira-Sánchez María del Rosario, García-Macías Celia, Alarcón-Jiménez Jorge, Martín Jiménez Ana, Gómez-Sánchez Sonia, De Bernardo Nieves and Sánchez-Jiménez Elena

J. Clin. Med. 2026, 15(4), 1482; https://doi.org/10.3390/jcm15041482 - 13 Feb 2026

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Abstract

Background/Objectives: Therapeutic exercise (TE) has been shown to be an effective tool for slowing physical and cognitive decline in patients with dementia. However, its true impact on physical and functional variables, as well as the duration of its effects once therapy is discontinued, remains unclear. The aim was to analyze the short- and medium-term effects of a structured and monitored TE program on motor function in patients with dementia. Methods: A pre–post clinical trial was conducted in individuals with a medical diagnosis of mild-to-moderate cognitive impairment (Mini-Mental State Examination scores between 10 and 23) who had not engaged in regular exercise during the previous 6 months. The study variables and their measurement tools included general motor function (Short Physical Performance Battery), trunk control (Trunk Control Test), balance (Berg Balance Scale), overall mobility and gait (Timed Up and Go Test), and degree of independence in activities of daily living (ADLs) (Barthel Index). Participants completed a 12-week TE intervention at moderate intensity, 3 days per week for 45 min sessions. The program included aerobic training and strength, coordination, flexibility, and balance exercises. TE intensity was monitored through heart rate and dynamic maximal resistance. Assessments were conducted at baseline (t0), immediately after the program (t1), and 6 months after completion (t2). Results: Significant global longitudinal effects of time were observed for general motor function, balance, trunk control, and mobility and gait, whereas no significant global effect was detected for independence in activities of daily living. Post-intervention changes were non-significant; however, several pairwise comparisons showed moderate-to-large effect sizes. Follow-up assessments revealed shifts in performance distributions consistent with functional decline. Conclusions: A structured TE program performed at moderate intensity may help slow or attenuate the physical decline experienced by individuals with dementia. Full article

(This article belongs to the Special Issue Neurological Rehabilitation: Repair Mechanisms, Plasticity, and Connectomes)

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15 pages, 414 KB

Open AccessArticle

The Effect of Aerobic Exercise Training on Patients with Type III Spinal Muscular Atrophy

by Sezan Mergen Kilic, Fatma Mutluay, Arman Cakar, Murat Giris, Hacer Durmus, Ilknur Bingul, Asuman Gedikbasi, Canan Kucukgergin, Zehra Oya Uyguner and Yesim Parman

J. Clin. Med. 2025, 14(17), 6087; https://doi.org/10.3390/jcm14176087 - 28 Aug 2025

Cited by 1 | Viewed by 1590

Abstract

Background: Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by variants in the SMN1 gene. This study investigates the functional and biochemical effects of moderate-intensity aerobic exercise in SMA Type III patients. Methods: Twenty-three patients aged 18–57 years were included in this study. The training group underwent a 12-week aerobic exercise program using a bicycle ergometer at 60–70% of their maximum heart rate three times per week for 30 min per session. The training continued for an additional four months. The primary outcome measures were the six-minute walk distance and oxygen uptake, both reflecting exercise capacity. Secondary outcome measures included muscle strength with dynamometer, functional performance, and fatigue with different scales. Furthermore, serum survival motor neuron (SMN) protein and insulin-like growth factor-1 (IGF-1) hormone levels were measured at baseline, post-training first measurement (after 12 weeks), and post-training second measurement (after 28 weeks). Results: The exercise group showed a significant increase in exercise capacity (p < 0.001) and 6MWT walking distance (p = 0.003). Furthermore, reduction in walking time in the 10-m walk test (p = 0.019) and improvements in strength of the right and left quadriceps (p = 0.004, p = 0.031) and right gastrocnemius (p = 0.034) muscles were identified. Furthermore, an improvement in the Fatigue Severity Scale (FSS) (p = 0.037) was found. SMN protein and IGF-1 levels were increased in the second measurement in the training group (p = 0.022 and p = 0.016, respectively). Conclusions: An aerobic exercise program improved physical function and muscle strength and reduced fatigue in SMA Type III patients, with sustained biochemical improvements. Aerobic exercise may serve as a beneficial adjunct therapy for this population. Full article

(This article belongs to the Special Issue Neurological Rehabilitation: Repair Mechanisms, Plasticity, and Connectomes)

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