Background: Multiple sclerosis (MS) is a disabling neurological disorder characterized by the existence of demyelinating lesions and affects more than 2.5 million people globally. The current approaches for patients with MS are mainly based on ameliorating symptoms and decreasing acute attacks, and so far, they have not been successful in providing effective neurological regeneration. Recently, natural-based therapies, like crocin, in light of their pharmacological and biological benefits, have acquired much attention in the treatment of neurological diseases like MS. Hence, this study attempts to answer the question of whether crocin therapy can be a suitable approach for MS with a mechanistic insight. Methods: In this narrative literature review, all related articles (in press and published) in English were searched and assessed using electronic databases, including Web of Science, PubMed, and Google Scholar, up to April 1, 2025. The search keywords in the title and/or abstract of articles were: "Crocin" or "Crocus Sativus" and "Multiple Sclerosis" or "MS". Results: Experimental evidence has revealed the ability of crocin to alleviate reflexive motor behavior-related tests, cognitive indices, depressive-like behavior, tail flick latency, the conduction velocity of the motor and sensory nerve, antioxidant factors, and to attenuate inflammatory factors. Besides improving some mental factors, such as anxiety, clinical outcomes indicated that crocin could modulate oxidative stress and inflammation-associated markers. Conclusion: The current preclinical and clinical studies have provided convincing evidence showing that crocin therapy can be a suitable candidate for MS cases; however, larger and more in-depth clinical trials are warranted to support these results.
Background: Stroke claims about 5.5 million lives annually, making it the second leading cause of death worldwide. In the United States (US), it is the fifth leading cause, trailing behind cardiovascular diseases (CVD) and cancer. Methods: This retrospective cohort study conducted at Valiasr Hospital in Arak City, Iran, focused on patients with stroke registered in Arak University of Medical Sciences. 153 patients were examined. Data on demographics, stroke types, financial items, and National Institutes of Health Stroke Scale (NIHSS), Barthel, and modified Rankin Scale (mRS) scores were collected. NIHSS, mRS, and Barthel scales were used to assess economical findings of hospitalization and the first trimester after discharge in private and governmental health settings. Data were analyzed through SPSS software for statistical analysis. Results: The study involved patients with a mean age of 69.53 [standard deviation (SD) = 13.4] years, who were hospitalized for about 4.97 days. Gender distribution was with women at 51% and men at 49%. After discharge, a significant majority (66%) received care exclusively from private settings, while 34% utilized both private and governmental services. In contrast, governmental settings showed no significant differences in costs related to NIHSS scores (P = 0.120). Similarly, Barthel scores indicated notable cost disparities in private settings at all stages (P = 0.0001), while governmental settings exhibited no significant differences post-discharge (P = 0.777). Conclusion: Our study reveals that patients primarily rely on private settings for post-discharge services, with costs largely borne by themselves. The financial burden of hospitalization is mostly covered by basic insurance.
Background: Psychological stress has been proposed as a trigger of multiple sclerosis (MS) onset, yet population-based evidence remains inconsistent across cultures. This study examined the association between major stressful life events and MS susceptibility in Northern Iran. Methods: In a case-control study conducted between 2023 and 2025 in Mazandaran Province, Iran, 300 patients with definite MS and 300 age-and sex-matched healthy controls were enrolled. Exposure to major stressful life events during the five years preceding disease onset (for cases) or interview (for controls) was assessed using the validated Persian version of the Environmental Risk Factor Questionnaire (EnvIMS-Q). Logistic regression was used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Results: Exposure to at least one major stressful life event was reported by 92.7% of MS cases and 62.7% of controls (P < 0.001). After adjustment for demographic variables, six independent stressors were significantly associated with MS: marital separation (OR = 8.95, 95% CI: 1.92-41.6), financial debt (OR = 4.72, 95% CI: 2.73-8.16), death of a close relative (OR = 3.57, 95% CI: 2.25-5.66), unemployment or financial dependency (OR = 4.19, 95% CI: 1.64-10.7), serious personal illness or injury (OR = 2.66, 95% CI: 1.64-4.32), and marriage (OR = 3.99, 95% CI: 2.15-7.40). The identification of marriage as a stressor is contextually novel and may reflect region-specific psychosocial pressures. Conclusion: Major life stressors appear to contribute to MS susceptibility, with certain stressors such as marriage showing culture-dependent associations. These findings provide new insight into sociocultural factors influencing MS risk in Iranian populations. These findings should be interpreted with caution and confirmed in longitudinal studies.
Background: Constipation is a common non-motor symptom (NMS) in Parkinson's disease (PD), affecting up to 70% of patients and reducing quality of life (QOL). Probiotics may improve bowel function via gut microbiota modulation and gut-brain axis regulation. This randomized, double-blind, placebo-controlled trial evaluated the efficacy of six-week multi-strain probiotic supplementation on constipation in Iranian patients with PD. Methods: Seventy-two patients with PD (aged 50-80 years, functional constipation per Rome IV criteria) were randomized 1:1 to probiotics or placebo. The probiotic capsule contained Lactobacillus acidophilus (L. acidophilus), Lactobacillus casei (L. casei), Lactobacillus rhamnosus (L. rhamnosus), Bifidobacterium lactis (B. lactis), Bifidobacterium longum (B. longum), and Bifidobacterium breve (B. breve) [1 × 10⁹ colony-forming unit (CFU) each, total 12 × 10⁹ CFU/day]. Dietary intake and physical activity were assessed and included as covariates in analysis of covariance (ANCOVA) models. Primary outcome was weekly spontaneous bowel movements (SBMs); secondary outcomes included Patient Assessment of Constipation-Quality of Life (PAC-QOL) and Unified Parkinson's Disease Rating Scale (UPDRS) Part III. Baseline demographic, clinical, dietary, and physical activity characteristics were comparable between groups. Results: The probiotic group showed a mean SBM increase of 3.41 versus 0.44 in placebo [between-group difference = 2.97, 95% confidence interval (CI): 2.46-3.53, P < 0.001]. PAC-QOL improved significantly (adjusted mean difference = -15.22, 95% CI: -22.32 to -8.11, P < 0.001). No significant changes were observed in UPDRS Part III. Conclusion: Six-week probiotic supplementation increased bowel movement frequency and improved constipation-related QOL in patients with PD, with good tolerability. Larger, multicenter trials are warranted to confirm efficacy and explore potential effects on systemic PD progression.
Background: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare neurodegenerative disorder characterized by early-onset cerebellar ataxia, spasticity, and distal amyotrophy. This descriptive retrospective case series focuses on patients with ARSACS from the Indian subcontinent, with disease durations exceeding 10 years. Methods: This case series included patients with typical clinical features of ARSACS who were evaluated in a single neurology unit between 2016 and 2022. Data on age at onset, illness duration at the last follow-up, and clinical manifestations were recorded. Electrophysiology reports, neuroimaging findings, and genetic testing results were reviewed. Functional disability documented at the last available clinical evaluation was recorded. Results: The study comprised eight Indian patients with ARSACS [male/female (M:F) = 5:3] from unrelated families. The age at onset was between 2-5 years of age, with walking difficulties being the initial symptom in all cases. The correct diagnosis was established after the first decade of life, with a mean age at diagnosis of 23 years (range: 17-30 years) and a mean time to diagnosis of 20 years (range: 14-27 years). Electrophysiological studies showed demyelinating sensorimotor neuropathy. Imaging revealed characteristic linear T2-hypointensities in the pons and cerebellar atrophy. Genetic testing identified novel homozygous sacsin molecular chaperone (SACS) gene variants. Conclusion: This study provides valuable insights into the clinical and genetic features of ARSACS in the Indian subcontinent. The time taken to establish the diagnosis ranged from 14 to 27 years in this series. Recognizing characteristic clinical and imaging findings may facilitate earlier diagnosis. The identification of novel genetic variants further expands our understanding of ARSACS.
Background: Chronic migraine (CM) is a debilitating neurological disorder often complicated by medication overuse (MO). While abobotulinumtoxinA (ABO-BoNT-A) is a well-established preventive treatment for CM, its molecular mechanisms are not fully understood. Emerging evidence suggests that neurotrophic tyrosine receptor kinase 2 (NTRK2), SRC kinase signaling inhibitor 1 (SRCIN1), and P2X4 purinergic receptor (P2X4R) are involved in migraine chronification and botulinum neurotoxin A (BoNT-A) function, but their roles in humans remain underexplored. This case series investigated changes in NTRK2, SRCIN1, and P2X4R gene expression in peripheral blood pre- and post-BoNT-A treatment and assessed associated clinical outcomes in patients. Methods: The messenger ribonucleic acid (mRNA) levels of NTRK2, SRCIN1, and P2X4R genes were analyzed in a sample of eight patients with CM and MO following BoNT-A treatment using quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, migraine characteristics were assessed using Migraine Disability Assessment Scale (MIDAS), Headache Impact Test-6 (HIT-6), and Patient Health Questionnaire-9 (PHQ-9). Results: The intervention resulted in early measurable improvements in migraine symptoms and disability. Post-treatment, P2X4R expression significantly increased (P < 0.05), while NTRK2 and SRCIN1 showed no significant changes. Conclusion: Findings indicate that P2X4R upregulation may be linked to the therapeutic effects of BoNT-A, while NTRK2 and SRCIN1 appear uninvolved. The trend in P2X4R expression suggests it may serve as a predictive biomarker and therapeutic target, but further validation in larger cohorts is necessary.
The posterior inferior cerebellar artery (PICA) typically arises from the intracranial V4 segment of the vertebral artery.1 However, its origin can exhibit considerable variation. Rare anatomical variants include origins from the basilar trunk, a common trunk shared with the anterior inferior cerebellar artery (AICA), meningeal branch of the vertebral artery, or even bilateral absence.1,2 Exceptionally rare are cases where the PICA arises from the internal carotid artery (ICA), a configuration that has important clinical implications due to its involvement in both anterior and posterior circulations. We report the case of a 77-year-old man who presented with acute-onset severe headache. Non-contrast computed tomography (CT) of the brain demonstrated interhemispheric hemorrhage. CT angiography subsequently revealed a distal anterior cerebral artery (DACA) aneurysm as the likely source of bleeding. To obtain detailed vascular anatomy and guide therapeutic planning, digital subtraction angiography (DSA) was performed prior to endovascular intervention. During DSA, DACA aneurysm was seen, but also we incidentally identified an unusual vascular anomaly: the right PICA arising from the proximal cavernous segment of the right ICA (Figure 1a and b).
Background: The global prevalence of Alzheimer’s disease (AD) has emerged as a paramount concern due to the aging population. The current research examines the effects of six-week high-intensity interval training (HIIT), with and without cannabidiol (CBD) supplementation, on cognitive decline, micro ribonucleic acid (miRNA)-124 expression levels, and the protein expression of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and nestin in the hippocampus of rats with amyloid beta (Aβ)-induced AD. Methods: 30 male Wistar rats were randomly divided into six groups: control (CNT), sham, Alzheimer (AD), Alzheimer + HIIT (H-AD), Alzheimer + CBD (C-AD), and Alzheimer + HIIT + CBD (CH-AD). Following the hippocampal injection of Aβ1-42, the HIIT protocol and CBD supplementation [20 mg/kg/day, per os (P.O.)] were initiated and conducted over six weeks. After the last intervention, the hippocampus tissues were collected to assess miRNA-124 expression levels and the protein expression of BACE1 and nestin. Results: HIIT alone and in combination with CBD treatment significantly improved cognitive impairment induced by AD. Moreover, both treatments significantly reduced BACE1 protein expression and increased nestin protein expression in AD rats. However, despite decreased miRNA-124 expression levels in the AD group in comparison with the CNT group, HIIT and CBD administration did not alter miRNA-124 expression levels in other groups. Conclusion: The findings can contribute to a higher understanding of the beneficial effects of HIIT combined with CBD administration in mitigating AD-induced cognitive impairment by reducing BACE1 protein expression and increasing nestin protein expression.
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 CH2Cl2 and 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.
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. Results: These phenotypes were classified into three 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.
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.
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. Results: 9 diagnostic miRNAs, including hsa-miR-107, 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.
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. Results: Among 728 patients with AIS included, 48.1% 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.
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.
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 oftDCS 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 oftDCS in aphasia rehabilitation.
Background: The major treatment regimens for multiple sclerosis (MS) are disease-modifying therapies (DMTs). Fungal, viral, and bacterial infections are common complications ofthese 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. Finally, data from 798 participants were analyzed. 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.
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.
