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Advances in Neurological Diseases: Pathogenesis, Diagnosis and Therapeutic Strategies

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: 31 May 2025 | Viewed by 1583

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Special Issue Editors

Dr. Foteini Christidi

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Guest Editor

Department of Neurology, School of Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, 68100 Alexandroupolis, Greece
Interests: neuroimaging; neuropsychology; cognitive disorders
Special Issues, Collections and Topics in MDPI journals

Dr. Dimitrios Tsiptsios

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Guest Editor

3rd Department of Neurology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Interests: epilepsy; clinical neurophysiology; stroke; neuromuscular disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neurological diseases encompass a broad and diverse array of conditions that affect the brain, spinal cord, and peripheral nerves. These disorders can present with a wide spectrum of symptoms, ranging from subtle cognitive changes to severe motor impairments, posing significant challenges to individuals and healthcare systems worldwide.

Comprehending the pathogenesis of neurological diseases is essential for developing effective treatments and preventive strategies. Advances in neuroimaging and biomarker discovery have significantly improved the early and accurate diagnosis of these diseases. Moreover, insights into the mechanisms underlying neurological diseases are pivotal for devising therapeutic strategies. The therapeutic strategies discussed in this Special Issue span a broad range of interventions, ranging from pharmacological treatments that target specific pathological pathways to innovative gene- and cell-based therapies, as well as non-pharmacological treatments.

We invite researchers to submit research articles or review papers relevant to this Special Issue. Areas of research may include but are not limited to the following: (1) molecular and cellular mechanisms; (2) diagnostic tools, biomarkers, and imaging techniques; (3) clinical and interventional studies, including pharmacological and regenerative medicine approaches, as well as neurorehabilitation methods, targeting both motor and extra-motor deficits.

We look forward to receiving your contributions.

Dr. Foteini Christidi
Dr. Dimitrios Tsiptsios
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

neurological diseases
neurodegenerative diseases
stroke
multiple sclerosis
epilepsy
neuromuscular disorders
demyelinating diseases
traumatic brain injury
clinical neurophysiology
neuroimaging
genetics
neuropsychological tests
molecular and cellular mechanisms
biomarkers
diagnosis and therapeutics
prognosis
neurorehabilitation

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Published Papers (3 papers)

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Research

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15 pages, 2427 KiB

Open AccessArticle

Role of Epidural Electrode Stimulation in Three Patients with Incomplete AIS D Spinal Cord Injury

by Yu-Chen Chen, Xiang-Ling Huang, Hung-Yu Cheng, Ciou-Chan Wu, Ming-Yung Wu, Lian-Cing Yan, Shin-Yuan Chen, Sheng-Tzung Tsai and Shinn-Zong Lin

Biomedicines 2025, 13(1), 155; https://doi.org/10.3390/biomedicines13010155 - 10 Jan 2025

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Abstract

Background/Objectives: To determine whether epidural electrical stimulation (EES) improves sensory recovery and walking function in patients with chronic spinal cord injury (SCI) with a grade on the American Spinal Cord Injury Association impairment scale (AIS) of C or D at the cervical level. Methods: Three individuals with cervical-level chronic AIS D SCI were enrolled in the study. The mean injury duration and age were 4.8 ± 4.5 (range: 1.5–10) and 56.7 ± 9 years, respectively. The participants received personalized electrical stimulation for 36 weeks and were evaluated for their SCI characteristics, the result of an AIS assessment according to the lower extremity sensorimotor scale, their muscle activity, and preoperative walking ability parameters, initially as well as at weeks 8 and 36 of the EES intervention. Results: Participants receiving EES significantly increased the muscle activity in most lower limb muscles. Regarding the AIS assessment of the lower extremities, one participant fully regained a light touch sensation, while two fully recovered their pinprick sensation (AIS sensory scores increased from 14 to 28). One participant achieved a full motor score, whereas the others’ scores increased by 19 and 7 points. Compared with preoperative gait parameters, two participants showed improvements in their walking speed and cadence. Walking symmetry, an important parameter for assessing walking function, improved by 68.7%, 88%, and 77% in the three participants, significantly improving the symmetry index (p = 0.003). Conclusions: Thus, EES may be an effective strategy for sensory impairment recovery, as well as muscular activity and strength improvement. These findings may facilitate stable walking in subjects with chronic incomplete SCI, but larger clinical trials are warranted. Clinical trial: NCT05433064. Full article

(This article belongs to the Special Issue Advances in Neurological Diseases: Pathogenesis, Diagnosis and Therapeutic Strategies)

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Figure 1
Graphical abstract. In this study, epidural electrical stimulation (EES) substantially increased muscle strength and improved sensory deficits and walking asymmetry. This indicates that EES may improve walking function in individuals with incomplete spinal cord injury. Full article ">Figure 2
EMG activity of spinal segmental mapping. sEMG response amplitude of muscle groups quantified through peak-to-peak measurements; sEMG responses were evoked with minimum EES amplitude. These results could be used to confirm the muscle group corresponding to the electrode configuration and obtain spinal segmental mapping information. The lower limb muscles stimulated include the iliopsoas, rectus femoris (RF), medial hamstring (MH), tibialis anterior (TA), and medial gastrocnemius (MG). Abbreviations: Amp., amplitude. Full article ">Figure 3
Implant location, configuration, and result of EES muscle stimulation. (A,D,G): Postoperative fluoroscopy and MR images in the sagittal view of the thoracic–lumbar spine, showing the location of the paddle electrode; yellow wavy lines indicate the paddle electrode. The implant locations of the three participants covered the region from thoracic spine 12 (T12) to lumbar spine 2 (L2). (B,E,H): The configurations and parameters of EES for evoking contractions in specific muscles of the lower limbs are displayed. Yellow and green squares indicate the anode and cathode, respectively. The lower limb muscles stimulated include the iliopsoas, rectus femoris (RF), medial hamstring (MH), tibialis anterior (TA), and medial gastrocnemius (MG). (C,F,I): EMG signals illustrating muscle activities in specific muscles without and with EES. The interval between EMG recordings without and with EES was 1 min. Gray and green colors represent EMG signals without and with EES, respectively. Full article ">Figure 4
Comparative analysis of clinical assessments and muscle activity pre- and post-EES intervention. (A,C,E): ASIA impairment scale scores for the lower extremities for each muscle. The diagrams on the left and right show the patient’s score on the AIS assessment pre- and post-EES intervention for 36 weeks. (B,D,F): The muscle activity corresponded to the mean of time- and amplitude-normalized RMS envelopes for 10 steps preoperatively and at week 8 and week 36 of treatment with EES. The same EES parameters were used at all assessment times. A device error resulted in missing preoperative EMG data for participant P1; thus, the Wilcoxon rank sum test was used to compare only the two treatment time points. * p < 0.05; ** p < 0.01; *** p < 0.001. The EMG activity of P2 and P3 analyzed using the Kruskal–Wallis test for multiple comparisons, followed by a post hoc Dunn’s test and Bonferroni adjustment. Asterisks indicate significant differences: * p < 0.016; ** p < 0.001. Full article ">Figure 5
Improvement trend in gait parameters at week 8 and week 36 of EES treatment. Gray line: participant P1; green line: participant P2; orange line: participant P3; blue line: average of all three participants; solid line: with EES; dashed line: without EES. p -value based on generalized estimation equations (GEEs). (A): increased speed in P1; an advance in P2 and P3 is not apparent (p = 0.09). (B): cadence outcomes showing a flat trend following EES (p = 0.294). (C): despite an increase in the symmetry index (SI) in the 8th week, indicating a greater degree of walking asymmetry than preoperatively, all participants showed an improvement in walking symmetry at 36 weeks (p = 0.003), with a level of symmetry superior to that observed preoperatively. Full article ">

Review

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38 pages, 2169 KiB

Open AccessReview

Sensory Dysfunction in ALS and Other Motor Neuron Diseases: Clinical Relevance, Histopathology, Neurophysiology, and Insights from Neuroimaging

by Jana Kleinerova, Rangariroyashe H. Chipika, Ee Ling Tan, Yana Yunusova, Véronique Marchand-Pauvert, Jan Kassubek, Pierre-Francois Pradat and Peter Bede

Biomedicines 2025, 13(3), 559; https://doi.org/10.3390/biomedicines13030559 - 22 Feb 2025

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Abstract

Background: The clinical profiles of MNDs are dominated by inexorable motor decline, but subclinical proprioceptive, nociceptive and somatosensory deficits may also exacerbate mobility, dexterity, and bulbar function. While extra-motor pathology and frontotemporal involvement are widely recognised in motor neuron diseases (MNDs), reports of sensory involvement are conflicting. The potential contribution of sensory deficits to clinical disability is not firmly established and the spectrum of sensory manifestations is poorly characterised. Methods: A systematic review was conducted to examine the clinical, neuroimaging, electrophysiology and neuropathology evidence for sensory dysfunction in MND phenotypes. Results: In ALS, paraesthesia, pain, proprioceptive deficits and taste alterations are sporadically reported and there is also compelling electrophysiological, histological and imaging evidence of sensory network alterations. Gait impairment, impaired dexterity, and poor balance in ALS are likely to be multifactorial, with extrapyramidal, cerebellar, proprioceptive and vestibular deficits at play. Human imaging studies and animal models also confirm dorsal column-medial lemniscus pathway involvement as part of the disease process. Sensory symptoms are relatively common in spinal and bulbar muscular atrophy (SBMA) and Hereditary Spastic Paraplegia (HSP), but are inconsistently reported in primary lateral sclerosis (PLS) and in post-poliomyelitis syndrome (PPS). Conclusions: Establishing the prevalence and nature of sensory dysfunction across the spectrum of MNDs has a dual clinical and academic relevance. From a clinical perspective, subtle sensory deficits are likely to impact the disability profile and care needs of patients with MND. From an academic standpoint, sensory networks may be ideally suited to evaluate propagation patterns and the involvement of subcortical grey matter structures. Our review suggests that sensory dysfunction is an important albeit under-recognised facet of MND. Full article

(This article belongs to the Special Issue Advances in Neurological Diseases: Pathogenesis, Diagnosis and Therapeutic Strategies)

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49 pages, 1487 KiB

Open AccessSystematic Review

The Impact of Visualization on Stroke Rehabilitation in Adults: A Systematic Review of Randomized Controlled Trials on Guided and Motor Imagery

by Andrea Calderone, Alfredo Manuli, Francesca Antonia Arcadi, Annalisa Militi, Simona Cammaroto, Maria Grazia Maggio, Serena Pizzocaro, Angelo Quartarone, Alessandro Marco De Nunzio and Rocco Salvatore Calabrò

Biomedicines 2025, 13(3), 599; https://doi.org/10.3390/biomedicines13030599 - 1 Mar 2025

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Abstract

Background/Objectives: Guided imagery techniques, which include mentally picturing motions or activities to help motor recovery, are an important part of neuroplasticity-based motor therapy in stroke patients. Motor imagery (MI) is a kind of guided imagery in neurorehabilitation that focuses on mentally rehearsing certain motor actions in order to improve performance. This systematic review aims to evaluate the current evidence on guided imagery techniques and identify their therapeutic potential in stroke motor rehabilitation. Methods: Randomized controlled trials (RCTs) published in the English language were identified from an online search of PubMed, Web of Science, Embase, EBSCOhost, and Scopus databases without a specific search time frame. The inclusion criteria take into account guided imagery interventions and evaluate their impact on motor recovery through validated clinical, neurophysiological, or functional assessments. This review has been registered on Open OSF with the following number: DOI 10.17605/OSF.IO/3D7MF. Results: This review synthesized 41 RCTs on MI in stroke rehabilitation, with 996 participants in the intervention group and 757 in the control group (average age 50–70, 35% female). MI showed advantages for gait, balance, and upper limb function; however, the RoB 2 evaluation revealed ‘some concerns’ related to allocation concealment, blinding, and selective reporting issues. Integrating MI with gait training or action observation (AO) seems to improve motor recovery, especially in balance and walking. Technological methods like brain–computer interfaces (BCIs) and hybrid models that combine MI with circuit training hold potential for enhancing functional mobility and motor results. Conclusions: Guided imagery shows promise as a beneficial adjunct in stroke rehabilitation, with the potential to improve motor recovery across several domains such as gait, upper limb function, and balance. Full article

(This article belongs to the Special Issue Advances in Neurological Diseases: Pathogenesis, Diagnosis and Therapeutic Strategies)

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