Current Journal of Neurology

Identification of diagnostic microRNAs and their target genes in multiple sclerosis based on interactome networks using an in silico approach

Azizeh Asadzadeh — 2026-01-04

Background: The most common demyelinating disease of nerve fibers in the brain and spinal cord is multiple sclerosis (MS) which is associated with several disabilities. By early diagnosis and treatment of MS, the progression of disability can be slowed down. For this purpose, our study aims to identify diagnostic micro ribonucleic acids (miRNAs) and their target genes in MS.

Methods: For the screening of up-regulated and down-regulated genes and miRNAs in patients with MS, GSE17846 (platform: GPL9040, 20 MS samples and 21 control samples), GSE108000 (platform: GPL570, 7 chronic active MS lesions, 8 inactive MS lesions, and 10 controls), and GSE135511 (platform: GPL6883, 20 cases of MS and 10 controls) were extracted from the Gene Expression Omnibus (GEO) database and analyzed based on criteria |log2 (fold change)| > 1 and P-value < 0.05. Protein-protein and miRNA-messenger ribonucleic acid (mRNA) interaction networks were constructed by Cytoscape version 3.9.1 and then, miRNAs and common target genes were detected in MS. Finally, functional enrichment analysis of common target genes was obtained.hsa-miR-574-5p, hsa-miR-1206, hsa-miR-142-3p, hsa-miR-1275, hsa-miR-140-5p, hsa-miR-1207-5p, hsa-miR-613, and hsa-miR-1258 were identified. We also detected 12 target genes for these miRNAs involved in MS. The genes were PLXDC2, Potassium voltage-gated channel subfamily C member 1 (KCNC1), FCGBP, MS4A6A, SNAP25, CCL2, FGF13, GABRG2, SLC5A3, KCNC2, MAL2, and HTR5A.

Conclusion: This research introduces miRNAs and their target genes associated with MS as biomarkers to develop new diagnostic and treatment methods. However, this research can be enhanced by additional validation procedures, such as in vitro and in vivo tests of these discovered biomarkers.

Expanding the phenotypic spectrum of RNASEH2B mutations: A new case of pure hereditary spastic paraplegia and a systematic review

Mohammad Reza Habibi-Kavashkohie — 2026-01-04

Background: Pathogenic variants in the RNASEH2B gene have been linked to Aicardi-Goutières syndrome type II (AGS-II), an early-onset encephalopathy that exhibits phenotypic overlaps with other neurodegenerative diseases, such as hereditary spastic paraplegia (HSP). A poor genotype-phenotype correlation, inconsistent findings in biomarker results of patients, and the challenge of distinguishing AGS-II from HSP underscore the necessity of performing comprehensive studies to address current difficulties in RNASEH2B-related cases. Here, through a detailed case report and comprehensive systematic review, we highlight clinical heterogeneity of RNASEH2B-related neurodegenerative cases and support the current view of considering RNASEH2B as an HSP-causing gene.

Methods: Using whole exome sequencing (WES), we identified an RNASEH2B variant, c.529G>A (p.Ala177Thr), in an Iranian patient suspected of having HSP, a mutation commonly reported in AGS-II. In contrast to AGS-II, clinical studies of the Iranian case were dominated by non-progressive HSP. A subsequent Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided review of RNASEH2B-related neurodegenerative disorders identified 49 relevant cases from 349 studies, revealing a variable spectrum of phenotypes. overlapping categories: “RNASEH2B-related AGS”, “atypical AGS-II”, and “RNASEH2B-related HSP”. 95 cases were diagnosed as RNASEH2B-related AGS or atypical AGS-II; six were classified as RNASEH2B-related HSP. One case was asymptomatic, and another involved intrauterine fetal death.

Conclusion: The current study highlights the expanding phenotypic spectrum of RNASEH2B mutations, emphasizing their potential to manifest as isolated pure HSP (pHSP) rather than classical AGS. This study underscores the importance of raising clinical awareness and incorporating genetic testing, particularly for atypical RNASEH2B cases.

Infections in patients with multiple sclerosis treated with disease-modifying therapies: A comparative risk assessment cohort study

Mohammad Reza Fattahi — 2026-01-04

Background: The major treatment regimens for multiple sclerosis (MS) are disease-modifying therapies (DMTs). Fungal, viral, and bacterial infections are common complications of these drugs. Also, MS itself is an immune-related chronic disease that can compromise their subjects to infections. Therefore, MS can be a risk factor for infectious complications.

Methods: This paper is a retrospective cohort study conducted from February 2020 to January 2022 using prospectively collected data from every patient registered at the Multiple Sclerosis Referral Research Center in Tehran, Iran. We inducted patients with MS who were diagnosed based on McDonald's criteria and exposed to DMTs for at least 6 months prior to this study. Being under 18 years of age, diagnosis change during the study, and mortality were the exclusion criteria of this study.

Results: We inducted a total of 979 patients into this study. Rituximab and natalizumab were associated with a higher risk of urinary tract infection (UTI) and bacterial vaginitis. Moreover, rituximab, glatiramer acetate, and dimethyl fumarate were associated with HSV-associated ulceration. None of the investigated DMTs were associated with an altered risk of COVID-19.

Conclusion: The use of DMTs can result in an increased risk of infections in patients. The selection of these DMTs should be based on their efficacy and risk of complications. Healthcare providers should familiarize themselves with these complications to select the appropriate DMTs with the highest efficacy.

Body mass index and cognitive recovery after acute ischemic stroke: A 3-month prospective analysis using mini-mental state examination at Tashkent Medical Academy, Uzbekistan

Feruza Shermuhamedova — 2026-01-04

Background: The association between body mass index (BMI) and cognitive recovery after acute ischemic stroke (AIS) remains controversial, with some studies suggesting a protective effect of overweight status. This study aims to investigate the relationship between BMI and cognitive recovery at three months post-stroke using data from the clinic of Tashkent Medical Academy, Tashkent, Uzbekistan.

Methods: We conducted a prospective cohort study including patients with AIS from the clinic of Tashkent Medical Academy between 2022 and 2024. Patients were categorized into five BMI groups based on World Health Organization (WHO) Asian population criteria. Cognitive recovery was assessed using the Mini-Mental State Examination (MMSE) at three months, with favorable recovery defined as an improvement of at least 3 points. Multivariate logistic regression and linear mixed-effects modeling (LMM) were used to evaluate the association between BMI and cognitive recovery, adjusting for demographic and clinical variables.

were overweight, 30.0% had normal weight, 13.5% were obese, 4.4% were underweight, and 4.1% were severely obese. Favorable cognitive recovery was most frequent in overweight patients (60.9%) and least common in underweight patients (50.0%) (P < 0.001). Overweight status was independently associated with better cognitive recovery [odds ratio (OR): 1.22, 95% confidence interval (CI): 1.10-1.37], whereas severe obesity showed no statistically significant association with cognitive outcomes (OR: 1.06, 95% CI: 0.71-1.58).

Conclusion: Overweight status may be associated with improved cognitive recovery after AIS, whereas severe obesity and underweight status are linked to worse outcomes. These findings highlight the need for individualized weight management strategies in post-stroke rehabilitation. Further research is needed to explore the underlying mechanisms and potential clinical interventions.

Effects of transcranial direct current stimulation on language recovery in chronic post-stroke aphasia

Yunika Khairina — 2026-01-04

Background: Aphasia is a major cause of long-term disability in post-stroke patients. Non-invasive brain stimulation, particularly transcranial direct current stimulation (tDCS), has shown promise in enhancing language recovery. However, evidence from Indonesia remains scarce. This study aimed to evaluate the effects of tDCS on language recovery in chronic post-stroke aphasia (PSA).

Methods: This quasi-experimental study included 30 patients with chronic PSA, divided into 2 groups: 15 received 5 sessions of tDCS combined with language training, while 15 underwent language training alone. Language abilities were assessed using the Tes Afasia untuk Diagnosis Informasi dan Rehabilitasi (TADIR) or Aphasia Test for Diagnostic Information and Rehabilitation at baseline, post-therapy, and 2 weeks post-therapy. Statistical analysis was conducted using the Friedman test.

Results: Participants (93.3% male) had a median age of 56 years (range: 33-65 years). The tDCS group showed significant improvements in TADIR subtests, including verbal fluency, word naming, speech rate, verbal comprehension, and writing (P < 0.05). The control group showed improvements in fewer subtests, namely verbal fluency, word naming, and repetition.

Conclusion: Combining tDCS with language training may enhance recovery in specific language domains, notably writing, among patients with chronic PSA. However, most between-group comparisons did not reach statistical significance, and findings should be interpreted as exploratory. Larger controlled trials are needed to establish the efficacy and clinical relevance of tDCS in aphasia rehabilitation.

The relationship between quantitative magnetic resonance imaging markers and clinical/cognitive assessments in patients with multiple sclerosis: A cross-sectional study

Habib Farahmand — 2026-01-05

Background: This study examines the relationship between quantitative magnetic resonance imaging (MRI) markers and clinical/cognitive performance in patients with multiple sclerosis (MS), exploring the impact of MRI markers on disability, clinical status, and cognitive function.

Methods: This cross-sectional study recruited patients with MS from the MS registry center of Rafsanjan University of Medical Sciences, Rafsanjan, Iran. Informed consent was obtained from all participants
(8 men, 57 women). Patients with MS underwent neuropsychological and clinical assessments using a word-pair learning task, the Wisconsin Card Sorting test (WCST), Tower of London test (TOL), Paced Auditory Serial Addition Test (PASAT), Multiple Sclerosis Functional Composite (MSFC), and the Expanded Disability Status Scale (EDSS). MRI markers were assessed by the neurologist and radiologist. Statistical significance was set at P < 0.05.

Results: Patients with plaques in the basal ganglia and thalamus had significantly different MSFC (P = 0.038) and PASAT (P = 0.010) scores, while higher EDSS scores correlated with T2-weighted-fluid-attenuated inversion recovery (T2-FLAIR) hyper-intense plaques (P = 0.025). T1 black hole plaques were associated with increased depression (P = 0.015). WCST scores were significantly higher in patients with infratentorial plaques (P = 0.006) and those with T1 black hole lesions (P < 0.05). Total plaque volume positively correlated with EDSS score (r = 0.386, P = 0.002) and word-pair learning (r = 0.254, P = 0.045), and negatively correlated with PASAT scores (r = -0.299, P = 0.017). Enhanced plaques correlated positively with TOL performance (r = 0.319, P = 0.010).

Conclusion: Memory decline and increased disability in patients with MS are associated with brain volume loss, increased plaque volume, and plaque location in the infratentorial region, basal ganglia, and thalamus. Enhanced plaques or T1 black hole lesions also contribute to cognitive impairment.

Transplantation of human glial cells into murine brains: A systematic review of efficacy and safety in neurodegenerative disorders

Sanjeev Kumar Jain — 2026-01-05

Background: Neurodegenerative diseases impact millions of individuals globally. Over the years, brain research has predominantly focused on neurons, but attention is now shifting to glial cells, the brain's support cells, which play a vital role in neurodegenerative disorders. Therefore, glial cell transplantation represents a groundbreaking treatment approach for various neurodegenerative disorders, with the potential to restore neuronal function. We evaluated the evidence on the therapeutic effectiveness of human glial cell transplantation in neurodegenerative disorders.

Methods: The literature review was performed in PubMed, Scopus, and Web of Science from 2000 to 2024. The authors independently reviewed the screened articles. The study outcomes on cell differentiation, long survival restoration of neuron function, and adverse outcomes were analyzed.

Results: Study results highlight promising findings, including astrocytes improving motor function and slowing disease progression in neurodegenerative animal models through neurotrophic factor secretion and reduced inflammation. Similarly, microglia transplantation has demonstrated effectiveness in reducing α-synuclein toxicity in Parkinson's disease (PD), removing amyloid-β plaques in Alzheimer's disease (AD) models, and enhancing neuronal survival. Additionally, in demyelinating pathologies like multiple sclerosis (MS), oligodendrocyte transplantation promotes remyelination, restoring axonal conduction and enhancing functional outcomes.Cografting astrocytes with neuro progenitor cells significantly improved dopamine neuron engraftment and survival for at least 6 months post-transplantation.

Conclusion: The transplantation of human glial cells offers promising therapeutic potential for neurodegenerative disorders, improving neuronal survival, restoring damaged circuits, and reducing disease progression.

Systematic review of curcumin-based optical imaging for amyloid-β detection in Alzheimer’s disease models

Kimia Safavian — 2026-01-05

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by amyloid-beta (Aβ) plaque accumulation and cognitive decline. Early and precise Aβ detection is vital for effective therapeutic intervention. Curcumin-based fluorescent probes offer high specificity, non-invasive imaging compatibility, and deep tissue penetration, making them promising tools for optical Aβ imaging. This systematic review evaluates preclinical studies on curcumin-based fluorescent probes to assess their photophysical properties, imaging capabilities, and potential applications in detecting Aβ plaques in mouse models of AD.

Methods: A comprehensive literature search was performed in PubMed and ScienceDirect (2000-2024). Eligible studies were original English-language articles using curcumin-based probes for optical imaging of Aβ in Alzheimer’s mouse models. Data extraction focused on imaging parameters such as binding affinity [dissociation constant (Kd)], emission wavelength, quantum yield, fluorescence enhancement, and delivery methods.

Results: Thirteen preclinical studies met the inclusion criteria and were analyzed. CRANAD-102 probe showed the highest binding affinity (Kd = 7.5 nM) while CRANAD-3 achieved the most significant fluorescence intensity (39.5-fold). Emission wavelengths averaged 690 nm, with longer wavelengths facilitating deeper tissue imaging. Quantum yields ranged from 0.011 to 0.40, with the highest yield (20.31) observed in CH₂Cl₂and effective doses averaging 2.0 mg/kg.

Innovative delivery methods, such as aerosolized formulations and micelle-based probes, expanded diagnostic applications, including non-invasive retinal imaging.

Conclusion: Curcumin-based fluorescent probes exhibit high specificity for Aβ aggregates, effective deep tissue imaging, and non-invasive delivery potential, making them promising tools for preclinical Alzheimer’s diagnostics. However, their clinical translation requires further validation in standardized preclinical and translational studies.

Mechanisms and clinical applications of the valsalva maneuver in migraine relief: A mini-review

Kamran Shirbache — 2026-01-05

Background: Migraine headaches (MH) are often managed with pharmacologic treatments, but there is growing interest in non-pharmacologic approaches that can reduce reliance on medications. The Valsalva Maneuver (VM) may offer a novel approach to managing MH.

Methods: We conducted a comprehensive literature review in this regard using Google Scholar and PubMed. The search focused on studies examining the relationship between VM and MH, various aspects of VM, and studies regarding migraine etiology.

Results: Our search reviewed 4,659 articles and included 57 that discussed the relevant topics. The findings suggest that VM may serve as an effective non-pharmacological technique for reducing MH severity. Several potential mechanisms may contribute to this event, including: 1- Autonomic Nervous System (ANS) Modulation: VM influences cardiac function and the trigeminovascular system (TVS), which are dysregulated in migraine patients. 2- Vascular Regulation: Abnormal vascular resistance in the dura mater and cerebral arteries, important in migraine pathophysiology, may be alleviated through VM-induced readjustment of vasodilation and modulation of the vasoconstrictor index (VI). 3- Intracranial Pressure and Neurochemical Modulation: Controversial but intriguing mechanisms suggest that VM regulates internal air pressure within the skull sinuses, manipulates cerebrospinal fluid (CSF) pressure, induces transient hypoxic effects, and triggers the release of endogenous pain modulators, all of which could contribute to shortening MH duration.

Conclusion: The VM demonstrates potential symptom-relieving benefits in MH, supported by both verified evidence and some unexplained findings. However, large-scale clinical trials on this topic are lacking to clarify the mechanism of the role of VM in MH and to establish a standardized protocol for its application.

Radiologically isolated syndrome accompanying hereditary neuropathy with liability to pressure palsies: A case report of a new demyelinating phenotype

Tugbanur Baytok — 2026-01-05

The Article Abstract is not available.