Immunogenicity, clinical efficacy, and safety of the sinopharm (BBIBP-CorV) SARS-CoV-2 vaccine among people with multiple sclerosis receiving disease-modifying therapies: a prospective cohort study.

BACKGROUND: To investigate the safety (adverse events [AEs] and post-vaccination multiple sclerosis [MS] activity within 6 weeks), clinical efficacy (protection against coronavirus disease 2019 [COVID-19]), and vaccine-induced humoral immunogenicity (SARS-CoV-2 neutralizing antibody, anti-nucleocapsid IgG, and anti-spike IgG) of the Sinopharm (BBIBP-CorV) vaccine among people with MS (PwMS) receiving different disease-modifying therapies (DMTs). METHODS: This prospective cohort study was conducted between November 2021 and May 2022. PwMS were followed for six months after the 2nd dose of vaccination. Antibody responses were measured 2-16 weeks after the 2nd dose injection. Multivariate logistic regression was employed to assess the impact of each DMT on dichotomous antibody responses, adjusting for age, sex, MS phenotype, expanded disability status scale, disease duration, and vaccination-antibody titration interval. RESULTS: Among the 261 screened PwMS, 209 (aged 38.23 ± 9.73 years, female: 70.8%; relapsing-remitting MS: 80.4%) were included. The frequencies of experiencing non-serious AEs and post-vaccination MS activity were 66.0% and 4.8%, respectively. Breakthrough COVID-19 infection was observed in 14.8% of the PwMS. A subcohort of 125 PwMS was assessed for antibody responses. Positive neutralizing antibodies, anti-nucleocapsid IgG, and anti-spike IgG were detected in 36.8%, 35.2%, and 52.0% of the PwMS, respectively. Multivariate regression indicated a 96% (OR: 0.04 [95% CI: 0.00, 0.51], P = 0.013), 93% (OR: 0.07 [0.01, 0.64], P = 0.019), and 89% (OR: 0.11 [0.01, 0.96], P = 0.045) reduced odds of positive neutralizing antibody, anti-nucleocapsid IgG, and anti-spike IgG, respectively, among fingolimod-receivers. Additionally, anti-CD20s-receivers had 88% (OR: 0.12 [0.02, 0.85], P = 0.034) lower odds of being positive for anti-nucleocapsid IgG. CONCLUSIONS: BBIBP-CorV appeared to be well tolerated in PwMS, with promising clinical efficacy. However, a suboptimal humoral response was observed in PwMS receiving fingolimod and anti-CD20s. Future research should investigate the relationship between humoral responses and the frequency and severity of COVID-19 infection across various DMTs.

Epidemiology of familial multiple sclerosis in Iran: a national registry-based study.

BACKGROUND: Admittedly, little is known about the epidemiological signatures of familial multiple sclerosis (FMS) in different geographical regions of Iran. OBJECTIVE: To determine the epidemiology and the risk of FMS incidence in several provinces of Iran with a different ethnic population including, Fars, Tehran, Isfahan (Persians), and Mazandaran (Mazanis), Kermanshah (Kurds), and Chaharmahal and Bakhtiari (Lors). METHODS: This cross-sectional registry-based study was performed on nationwide MS registry of Iran (NMSRI) data collected from 2018 to 2021. This system, registers baseline characteristics, clinical presentations and symptoms, diagnostic and treatments at regional and national levels. RESULTS: A total of 9200 patients including, 7003 (76.1%) female and 2197 (23.9%) male, were participated. About 19% of patients reported a family history of MS; the order from highest to lowest FMS prevalence was as follows: Fars (26.5%), Chaharmahal and Bakhtiari (21.1%), Tehran (20.5%), Isfahan (20.3%), Mazandaran (18.0%), and Kermanshah (12.5%). Of all FMS cases, 74.7% (1308 cases) were female and 25.3% (442 cases) were male. FMS occurrence was much more common in females than males (P-value = 0.001). Further, the mean age at onset was 30 years among FMS cases. A substantially higher probability of relapsing-remitting MS and secondary-progressive MS was found among FMS cases than sporadic MS (SMS) (P_value = 0.001). There was no significant difference in Expanded Disability Status Scale (EDSS) scores between FMS and SMS. The majority of FMS cases were observed among first-degree relatives, with the highest rate in siblings. There was a significant association between MS risk and positive familial history in both maternal and paternal aunt/uncle (P_value = 0.043 and P_value = 0.019, respectively). Multiple sclerosis occurrence among offspring of females was higher than males (P_value = 0.027). CONCLUSIONS: In summary, our findings imply a noteworthy upward trend of FMS in Iran, even more than the global prevalence, which suggests a unique Atlas of FMS prevalence in this multi-ethnic population. Despite the highest rate of FMS within Persian and Lor ethnicities, no statistically significant difference was observed among the provinces.

Dietary fish intake and the risk of multiple sclerosis: a systematic review and meta-analysis of observational studies.

Objectives: There is some inconclusive evidence for the role of fish consumption in susceptibility to multiple sclerosis (MS). The present study aimed to systematically review and determine the association between dietary fish intake and risk of MS.Methods: A systematic search with related keywords was carried out in PubMed-MEDLIN, Scopus-EMBASE, and OVID-MEDLINE from inception up to September 2019 to find observational studies that evaluated the association between dietary fish intake and the risk of MS. Random effect and subgroup analyses were performed to calculate pooled estimates at 95% CIs.Results: Six articles met the inclusion criteria for systematic review and meta-analysis. The results of this study indicated that the consumption of fish decreases the risk of MS [OR (95% CIs): 0.77 (0.64, 0.92); p-value = 0.004; I2 = 54.7%] compared with controls.Discussion: Dietary intake of at least 0.5 servings of fish per week during adolescence and after might reduce the risk of MS; however, further studies are required to prove this preventive effect.

The effects and side effects of laquinimod for the treatment of multiple sclerosis patients: a systematic review and meta-analysis of clinical trials.

PURPOSE: Although studies have shown the efficacy of laquinimod (LAQ) on disease progression in patients with multiple sclerosis (MS), there is some controversy about whether it improves the types of outcomes and side effects. The main purpose of the present study was to systematically review and meta-analyze the efficacies and side effects of LAQ in patients with relapsing-remitting MS (RRMS). METHODS: PubMed, Scopus, and Web of Science databases were searched with relevant keywords for articles published up to June 2019. Six randomized control trials that examined LAQ vs. placebo in adult patients with MS were included. Information on the effectiveness and side effects of LAQ were extracted. The quality of the included studies was appraised using Jadad scores, and the data were divided into subgroups according to different doses and periods. RESULTS: Efficacy of LAQ: The number of Gadolinium-enhancing (GDE) lesions significantly decreased after treatment with LAQ (SMD = -0.15, 95% CI: -0.23, -0.07), but there was no significant reduction in the number of T2 lesions (SMD = -0.38, 95% CI: -1.04, 0.28). The relapse rate (SMD = -0.13, 95% CI: -0.21, -0.04) and MS Functional Composite (MSFC) score significantly decreased with LAQ treatment (SMD =0.14, 95% CI: 0.05, 0.23). Risk of adverse events: The risk of diarrhea, nausea, abdominal pain, and all adverse events did not significantly increase (p > 0.05) with treatment with LAQ; however, the risk of back pain, headache, and vomiting significantly increased (p < 0.05). The change in mortality rate was not significant (OR = 0.25, 95% CI: 0.04, 1.50). CONCLUSIONS: LAQ can considerably improve clinical and imaging outcomes in RRMS patients. The most effective dose of LAQ with lower side effects may be 0.6 mg/day for at least 2 years, but more evidence is needed to confirm these results.Laquinimod can improve clinical and imaging outcomes in patients with multiple sclerosis.Back pain and headache are probable side effects of laquinimod in patients with multiple sclerosis.The most effective and safe dose of laquinimod for patients with multiple sclerosis may be 0.6 mg/day for 2 years.

The effect of minocycline on indolamine 2, 3 dioxygenase expression and the levels of kynurenic acid and quinolinic acid in LPS-activated primary rat microglia.

Microglia are one of the most important neural cells in the central nervous system (CNS) which account for 10-15% of all cells found in the brain. A vast majority of studies indicate that microglia play a pivotal role in protection and damage of the CNS. It has been shown that microglia are mainly scavenger cells but also produce a barrage of factors that are involved in tissue repair and neural regeneration. Several lines of evidence indicate that unregulated activation of microglia in response to either endogenous or exogenous insults results in the production of toxic factors that propagate neuronal injury. Studies demonstrated that the activated microglia secret the excessive amounts of quinolinic acid (QA) and kynurenic acid (KYNA) which are highly toxic for the neuronal cells. In line with this, indolamine 2, 3 dioxygenase (IDO), an enzyme producing KYNA and QA has been shown to be elevated during the inflammation in microglia. In this study, we established primary microglial cell cultures obtained from cerebral cortices of 1-day neonatal Wistar rats. Minocycline (20-60 µM) or its vehicle was added to the culture media 60 min prior to 48 h incubation with lipopolysaccharide (LPS; 10 ng/mL). Using a specific process of adhesion and shaking of the cultured glial cells, a purified culture of approximately 94% enriched microglia was obtained and then, corroborated by immunocytochemistry (ICC). The cell viability after minocycline treatments was assessed using the MTT colorimetric assay. The expression of IDO was evaluated using qPCR. The levels of KYNA and QA were determined using enzyme-linked immunosorbent assay (ELISA). The results showed that minocycline significantly decreased the levels of both KYNA and QA in glia cells exposed to LPS. Moreover, minocycline decreased the expression of IDO in treated LPS-induced microglia. It seems that minocycline has a potent ability to oppress the inflammatory process via the decrease in production of IDO expression and the concentrations of KYNA and QA.

Cerebral Hyperperfusion Syndrome, an Unusual but Disastrous Complication of Carotid Recanalization: A Case Report.

Cerebral hyperperfusion syndrome (CHS), known as the dark side of carotid recanalization, happens in about 0%-3% of patients. Unfortunately, physicians involving in carotid recanalization generally are not aware of diagnostic and therapeutic aspects of this unusual but potentially life-threatening disorder. Severe bilateral carotid stenosis is suggested to predispose patients to CHS by decrement of cerebrovascular reactivity in a setting of chronic hypoperfusion state. We here introduced such a case; a 69-year-old man, a known case of hypertension and ischemic heart disease, who developed progressive intracranial hypertension underlying CHS after carotid stenting because of symptomatic severe bilateral carotid stenosis.

Memantine for Prophylactic Treatment of Migraine Without Aura: A Randomized Double-Blind Placebo-Controlled Study.

BACKGROUND: Uncontrolled studies in human have suggested that memantine might be a suitable option for migraine prophylaxis. OBJECTIVE: To assess the efficacy and tolerability of memantine for migraine prophylaxis. METHODS: This was a 12-week randomized double-blind placebo-controlled parallel-group study. Sixty patients with migraine without aura were randomized using a computer-generated list to receive memantine (10 mg/day) or placebo for 12 weeks. The primary outcome was the difference in change from baseline in the monthly attack frequency at week 12 between the two groups (using migraine diary). Secondary efficacy measures were assessed using several clinical, functional, and psychological instruments. We performed both complete case (CC) and intention-to-treat analyses (ITT). RESULTS: Twenty-five patients in the memantine group and 27 patients in the placebo group completed the study. Patients in the memantine group showed significantly greater reduction (mean change; 3.4; 95%CI, 2.3-4.4) in the monthly attack frequency than the placebo group (mean change, 1.0; 95%CI, 0.3-1.7) (mean difference [MD], 2.3; 95%CI, 1.1-3.5, P < .001). Both CC (MD, 4.9; 95%CI, 2.6-7.2 days), and ITT analyses (MD, 5.2; 95%CI, 2.0-8.5) showed significantly higher reduction in the mean number of migraine days in the memantine group than the placebo group (P < .01). Patients in the memantine group experienced greater reduction in the number of work absence days, severity, and disability score than the patients in the placebo group in both ITT and CC analyses. Changes in quality of life, sleep, depression, and anxiety did not differ between the two groups. Three patients in the memantine group complained of sedation, mild vertigo and nausea, and drowsiness. In the placebo group, one patient complained of nausea and another patient discontinued treatment after 2 weeks due to vertigo. CONCLUSION: Memantine might be a tolerable and efficacious option for prophylaxis in patients with migraine without aura. Tolerability, short duration required for titration, and safety profile in pregnancy might give memantine an advantage over other antimigraine medications. The study was registered in the Iranian Registry of Clinical Trials (Registration number: IRCT2013120115616N1).

Immunosuppressive Drugs, an Emerging Cause of Posterior Reversible Encephalopathy Syndrome: Case Series.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a well-recognized complication of hypertensive encephalopathy. Recently, pre-eclampsia, connective tissue disorders, and immunosuppressive drugs have been reported to be the etiologies of this rare syndrome. METHODS: We evaluated 9 cases of PRES whose diagnosis were confirmed based on clinical and radiologic evidence between July 2011 and December 2013 in a tertiary center, Imam Khomeini Hospital, Tehran, Iran. RESULTS: Immunosuppressive drugs, especially cyclosporine, and hypertension were the main precipitating factors. In this study, seizure was the most common clinical presentation (100%), whereas other common clinical presentations were confusion (78%), visual loss (67%), and headaches (67%). With conservative management and elimination of predisposing factor, the patients improved gradually except for 2 cases who experienced prolonged recovery period because of delayed diagnosis. CONCLUSIONS: With timely diagnosis, PRES generally has a good prognosis with complete recovery. However, in missed conditions, it could be associated with catastrophic burden especially in organ transplantation after a prolonged time spending to find matched donors or in chronic immunosuppressive conditions. Thereupon, physicians should be aware of clinical and radiologic manifestations of this preventable but potentially disabling syndrome.

Association study of cathepsin D gene polymorphism in Iranian patients with sporadic late-onset Alzheimer's disease.

One of the most prevalent forms of dementia is Alzheimer's disease (AD). Complex inheritance and multifactorial patterns of late-onset AD (LOAD) along with its heterogeneity are due to the presence of different AD-predisposing genes with different influence on disease development among various populations. A key event in the pathogenesis of AD is the deposition of ß-amyloid peptide, which is derived from the amyloid precursor protein by ß- and γ-secretases. Cathepsin D (CTSD) is an acid protease with ß- and γ-secretase-like features in vitro. An exonic C→T polymorphism at position 224 of the CTSD gene (rs: 17571) has been shown to be associated with the enzyme function of CTSD and with AD. Two studies in the German population reported a strong association of this polymorphism with an increased risk of developing AD, while other studies did not confirm this observation. We tested for this association in a case-control study in 100 Iranian sporadic LOAD patients based on diagnostic criteria of DSM-IV-TR and NINCDS-ADRDA and in 100 normal controls without any personal and family history of AD or other related dementias. Polymerase chain reaction-restriction fragment length polymorphism was set up to detect this polymorphism. Our study demonstrated that T-carrying genotype frequency in AD patients is significantly higher than in controls and there was a 2.5-fold increased risk for developing AD in the T-carrying genotype compared to C/C genotype (odds ratio = 2.5, p = 0.010). The odds ratio for subjects with the apolipoprotein E ε4 (APOE ε4) allele was 2.91 (p = 0.003) and carriers of the CTSD T and APOE ε4 alleles had a 6.25-fold increased risk of the disease (p = 0.0). Our results indicate that CTSD genotype is associated with the disease and a combination of the above risk factors significantly alters the risk for developing AD.

Evaluation of plaque detection and optimum time of enhancement in acute attack multiple sclerosis after contrast injection.

BACKGROUND: Magnetic resonance imaging (MRI) is important in the early diagnosis of novel or relapsing multiple sclerosis (MS). In addition, the optimal MRI protocol plays an important role in detecting MS plaques. PURPOSE: To find the best time to detect MS plaques on MRI after Gadobutrol injection. MATERIAL AND METHODS: Sixty-two relapsing-remitting type MS patients, (56 women, 6 men) with the mean age of 31 ± 7 years were enrolled into this study. The patients underwent T1-weighted MRI scan without contrast agents. Subsequently, Gadobutrol was injected (0.1 mmol/kg) and MRI scanning was repeated after 30 s, 5, 10, 15, and 30 min of Gadobutrol injection. The size, signal intensity, and enhancement pattern were determined for each plaque by contrast-enhanced T1-weighted images. RESULTS: Enhancing plaques were seen in 42 out of 62 patients. The mean number of enhancing plaques was 4 ± 8 plaques after 30 s of contrast injection. This figure increased to 7 ± 13 plaques after 15 min and 6 ± 10 plaques after 30 min. The signal intensity and size of plaques increased progressively, and the maximum signal intensity and plaque size were seen after 30 min (P < 0.001). CONCLUSION: The maximum number of enhancing plaques in MS patients was detected 15 min after contrast agent administration and the size and signal intensity of the lesions also increased remarkably at this time.

The cost-utility analysis of adding ocrelizumab to the treatment plan for primary progressive multiple sclerosis in Iran.

BACKGROUND: This study evaluates the cost-effectiveness of adding ocrelizumab to supportive care for primary progressive multiple sclerosis (PPMS) in Iran. RESEARCH DESIGN AND METHODS: Using a lifetime horizon from the payer's perspective, we developed a decision analytic model with Expanded Disability Status Scales (EDSS) as Markov health states while taking transition probabilities and treatment effects into account. Data were sourced from clinical trials and other literature. The target population was PPMS patients receiving either supportive care or ocrelizumab. We assessed cost- effectiveness through total costs, quality-adjusted life-years (QALYs), and the incremental cost- effectiveness ratio (ICER). Sensitivity analyses addressed uncertainties. RESULTS: The addition of ocrelizumab to supportive care provided an incremental gain of 0.89 QALYs and an additional cost of US$76,771.34, resulting in an ICER of US$86,220.35 compared to supportive care, which is 5.2 times Iran's GDP per capita (US$16,557). Thus, ocrelizumab is not cost-effective at the threshold of one time GDP per capita. However, the probability of cost-effectiveness increases at higher thresholds. Sensitivity analyses confirmed the robustness of the results. CONCLUSION: While ocrelizumab is not cost-effective at the threshold of one-time GDP per capita, its clinical benefits are significant. Formulating healthcare policies for high-cost medications with low alternatives like ocrelizumab is essential.

The Effect of Rituximab on the Cognitive Function of Patients with Relapsing-Remitting Multiple Sclerosis.

PURPOSE: Cognitive impairment can begin in the early stages of multiple sclerosis (MS). No medicine has been approved for treating cognitive impairment in MS patients. There is a lack of data on the role of rituximab in managing cognitive impairment in MS patients. Using minimal assessment of cognitive function in MS (MACFIMS), this study aims to investigate the effect of rituximab on the cognitive status of relapsing-remitting MS (RRMS) patients. METHODS: In this pre-post interventional trial, 28 eligible RRMS patients participated. They were administered rituximab for a year. Cognitive tests (MACFIMS), MS neuropsychological questionnaire (MSNQ), and Beck depression inventory-fast screen (BDI-FS) scores were evaluated at baseline, six, and 12 months following rituximab administration. FINDINGS: Eighteen participants with a mean age of 40.5 ± 12.91, 7 men, completed all three follow-ups. There was no statistically significant change in BDI-FS, MSNQ, Paced Auditory Serial Addition Test (P: 0.743), Symbol Digit Modalities Test (P: 0.711), Brief Visual Memory Test (BVMT) (P: 0.426), learning BVMT (P: 0.268), and delayed recall BVMT (P: 0.394) scores. However, the California Verbal Learning Test (CVLT), CVLT learning, and Controlled Oral Word Association Test scores significantly improved by 45.2% (P < 0.001), 12.3% (P: 0.013), and 26.7% (P: 0.011), respectively, 6-month follow-up rituximab treatment. There was a significant improvement in CVLT (+55.7%, P < 0.001), CVLT learning (+15.9%, P: 0.011), and delayed recall CVLT (+28%, P: 0.022) scores 12-month follow-up rituximab treatment. IMPLICATIONS: Rituximab prevents cognitive deterioration and improves some cognitive functions. Further investigations with a larger sample size, longer follow-ups, and inclusion of a placebo or another treatment arm are recommended.

Consanguineous marriage among familial multiple sclerosis subjects: A national registry-based study.

Background: The rising prevalence of familial multiple sclerosis (MS) in Iran has spurred interest in the potential impact of parental consanguinity on the risk of developing the disease. This study aims to aggregate current knowledge on parental consanguinity and its possible effect on MS risk, particularly among familial MS patients from various regions and ethnicities in Iran. The objective is to enhance the understanding of MS genetics and encourage further research in this field. Materials and methods: A cross-sectional study was conducted on clinically definite familial MS (FMS) patients registered in the nationwide MS registry of Iran (NMSRI). Data were extracted and supplemented with structured telephone follow-ups to gather detailed histories of MS in relatives and the familial relationships of the patients' parents. A family penetration score was proposed. Descriptive statistics and inferential statistical tests were used to analyze the data at a significance level of 0.05, adhering to ethical guidelines. Results: Out of 19,911 individuals registered in the NMSRI, 2307 FMS patients across 13 provinces were included in the final analysis. Among these, 385 (19.3 %) reported parental consanguinity, with 283 (14.2 %) having parents who were cousins and 102 (5.1 %) having parents who were distant relatives. The data showed no significant association between parental kinship and variables such as MS phenotype, number of affected relatives with MS, hospitalization rates, and expanded disability status scale score. Similarly, MS severity did not differ based on parental consanguinity (P-value >0.05). While the rate of consanguineous marriage was higher among patients with an onset age less than 18 years, there was no statistically significant difference in disease onset age based on parental consanguinity status. Conclusion: Our study highlights the complexity of factors influencing MS development, including genetic and environmental components. These results highlight the need for further research to achieve a more comprehensive understanding of MS etiology.

Time interval between the onset of symptoms and diagnosis of multiple sclerosis and the influential factors: A national registry-based study.

OBJECTIVE: The time to diagnosis of multiple sclerosis (MS) is of great importance for early treatment, thereby reducing the disability and burden of the disease. The purpose of this study was to determine the time from the onset of clinical symptoms to the diagnosis of MS and to evaluate the factors associated with a late diagnosis in Iranian MS patients. METHODS: The present cross-sectional study was conducted on patients with MS who were registered in the National MS Registry System of Iran (NMSRI). RESULTS: Overall, 23291 MS patients registered in 18 provinces of Iran were included in this study. The mean (standard deviation) interval between the onset of the disease and diagnosis of MS was 13.42 (32.40) months, and the median was one month. The diagnostic interval of 41.6% of patients was less than one month, and 14.8% of them had a one-month time to diagnosis. Patients with an age of onset below 18 years and those diagnosed after the age of 50 years had a longer time to diagnosis (P<0.001). Patients with primary progressive MS (PPMS) had the longest time to diagnose and those with relapsing-remitting MS (RRMS) had the shortest time (P<0.001). The results of negative binominal regression showed that the average rate of delay in diagnosis in women was 12% less than that in men. The average delay in diagnosis in patients with a positive family history of MS was 23% more than that in others. The rate of delay in the diagnosis of patients with PPMS and secondary progressive MS was 2.22 and 1.66 times higher, respectively, compared with RRMS. CONCLUSION: The findings of the present study revealed that more than half of the MS patients were diagnosed within a one-month interval from the symptom onset, which is an acceptable period. More attention should be paid to patients' access to medical facilities and MS specialists.

The association of serum carnitine levels with severity of fatigue in patients with multiple sclerosis: A pilot study.

Background: Fatigue is a common complaint of patients with multiple sclerosis (MS), adversely affecting their quality of life. There is a lot of evidence showing that carnitine deficiency is linked to fatigue development and severity in some conditions. This study aimed to evaluate the association between free L-carnitine serum levels and the severity of fatigue in patients with MS. Methods: This case-control study included 30 patients with relapsing-remitting MS (RRMS) in two age-matched equal-number groups according to the presence or absence of fatigue. Fatigue was scored using the valid questionnaire of Fatigue Severity Scale (FSS) and serum level of free L-carnitine was measured simultaneously. Finally, the association between serum level of free L-carnitine and fatigue severity was evaluated in patients with MS. Results: The mean value of FSS in patients with fatigue was 48.80 ± 8.55, which was nearly two-fold higher than the group without fatigue. We found a significant correlation between the serum level of free L-carnitine and FSS and showed that the patients with fatigue had a significantly lower serum level of free L-carnitine compared to patients without fatigue (P < 0.001). Conclusion: Present study demonstrated that patients with lower serum levels of free L-carnitine were more likely to experience fatigue. We recommend that a higher dietary intake of carnitine might be a useful complementary treatment for MS-related fatigue.

Biomechanical changes of the common carotid artery and internal jugular vein in patients with multiple sclerosis.

PURPOSE: Investigations of the hemodynamic changes of the venous system in patients with multiple sclerosis (MS) have shown contradictory results. Herein, the biomechanical parameters of the internal jugular vein (IJV) and common carotid artery (CCA) of MS patients were extracted and compared to healthy individuals. METHODS: B-mode and Doppler sequential ultrasound images of 64 IJVs and CCAs of women including 22 healthy individuals, 22 relapsing-remitting multiple sclerosis (RRMS) patients, and 20 primary-progressive multiple sclerosis (PPMS) patients were recorded and processed. The biomechanical parameters of the IJV and the CCA walls during three cardiac cycles were calculated. RESULTS: The IJV maximum and minimum pressures were higher in the MS patients than in the healthy subjects, by 31% and 19% in RRMS patients and 39% and 24% in PPMS patients. The venous wall thicknesses in RRMS and PPMS patients were 51% and 60% higher than in healthy subjects, respectively. IJV distensibility in RRMS and PPMS patients was 70% and 75% lower, and compliance was 40% and 59% lower than in healthy subjects. The maximum intima-media thicknesses of the CCAs were 38% and 24%, and the minimum intima-media thicknesses were 27% and 23% higher in RRMS and PPMS patients than in healthy individuals, respectively. The shear modulus of CCA walls in RRMS and PPMS patients was 17% and 31%, and the radial elastic moduli were 47% and 9% higher than in healthy individuals. CONCLUSION: Some physical and biomechanical parameters of the CCA and IJV showed significant differences between MS patients and healthy individuals.

Trail Making Test Could Predict Impairment in Cognitive Domains in Patients with Multiple Sclerosis: A Study of Diagnostic Accuracy.

OBJECTIVE: Cognitive impairment (CI) and executive dysfunction (ED) are prevalent in patients with multiple sclerosis (PwMS). The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) is the gold standard neuropsychological battery (NPB) for detecting CI. Delis-Kaplan Executive Function System (DKEFS) NPB evaluates ED. We aimed to find practical test(s) from DKEFS with acceptable diagnostic utility for early detection of impairment in cognitive and executive domains. METHODS: Cognitive and executive tasks, physical disability, and depression scores of 30 PwMS were assessed (17 women, age: 38.1). Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and Controlled Oral Word Association Test (COWAT) from MACFIMS and Trail Making Test (TMT), Design Fluency Test (DFT), and Verbal Fluency Test (VFT) from DKEFS were selected. The association between patients' characteristics and performance in tests, and diagnostic accuracy of DKEFS tests in detecting impairment in cognitive tasks were evaluated, using Pearson correlation and receiver operator characteristic curve analyses, respectively. RESULTS: A significant correlation was found between disease duration and SDMT and TMT subtests. Expanded Disability Status Scale was significantly related to SDMT, VFT-switching, and TMT subtests. Beck Depression Inventory was significantly related to DFT. TMT-switching detected abnormalities in SDMT and PASAT with 100% sensitivity, 93.3% (for SDMT), and 85.7% specificity (for PASAT). TMT-letter showed 100% sensitivity and 90% specificity in identifying abnormalities in COWAT. CONCLUSIONS: TMT, particularly the switching condition, is a practical paper-based test that could predict impairment in cognitive tasks. Clinicians may use TMT as a screening tool among PwMS.

Late-onset multiple sclerosis in Iran: A report on demographic and disease characteristics.

BACKGROUND: Today, it is estimated that around 5% of multiple sclerosis (MS) patients are in the late-onset category (age at disease onset ≥ 50). Diagnosis and treatment in this group could be challenging. Here, we report the latest update on the characteristics of Iranian patients with late-onset MS (LOMS). METHODS: This cross-sectional study used the information provided by the nationwide MS registry of Iran (NMSRI). The registrars from 14 provinces entered data of patients with a confirmed diagnosis of MS by neurologists. Patients with disease onset at or later than 50 years of age were considered LOMS. RESULTS: Of 20,036 records, the late-onset category included 321 patients (1.6%). The age-standardized LOMS prevalence was around 75 per 100,000 people. 215 patients (67%) were female. Median Expanded Disability Status Scale (EDSS) was 3 (interquartile range: 1.5-5). The majority of the cases (56%) suffered from relapsing-remitting (RR) course while 20% were diagnosed with primary progressive (PP) MS. Significantly higher proportion of male sex, PPMS, and higher EDSS were seen in the late-onset group compared with early-onset and adult-onset cases (p-value < 0.05). Seventy-five (23%) patients did not receive any disease-modifying treatment. DISCUSSION: The more prominent degenerative pathology of LOMS may be the underlying mechanism of the observed differences in comparison to non-LOMS. CONCLUSION: There are substantial differences and knowledge gaps regarding LOMS which could be the subject of further research.