Management of seizures in patients with multiple sclerosis; an Iranian consensus.

PURPOSE: Cooccurrence of a seizure in a patient with multiple sclerosis (MS) may complicate the management process. Questions, which may complicate the management process of a patient with MS and seizure, include "how should we approach to the patient", "how should we treat the patient", "how should we modify the patient's MS treatment strategy", etc. METHODS: We searched the electronic database PubMed on March 30, 2018 for articles in English that included the following search terms: "epilepsy" AND "multiple sclerosis" or "seizure" AND "multiple sclerosis" since 2013, to obtain the best recent relevant scientific evidence on the topic. A working group of 6 epilepsy and 5 MS experts took part in two consensus workshops in Tehran, Iran, in 2018. The final consensus manuscript was prepared and approved by all participants. RESULTS: The search with words "seizure" and "multiple sclerosis" yielded 121 entries; 10 were relevant to the topic. The search with words "epilepsy" and "multiple sclerosis" yielded 400 entries; 7 were relevant to the topic. We reviewed these 17 articles and also some other references, derived from these articles or relevant to the topic, for the purpose of our review. CONCLUSION: Cooccurrence of a seizure in a patient with MS may complicate the management process. In this review, we tried to provide answers to the frequently asked questions, considering the best available scientific evidence and expert opinion.

Prevalence of multiple sclerosis in Iranian emigrants: review of the evidence.

Iran has the highest prevalence of multiple sclerosis (MS) in the Middle East and Asia. Rate of emigration has been significantly raised among Iranians and though, multiple studies have been published on prevalence of MS among Iranian emigrants. Here we systematically reviewed these publications. We performed a comprehensive literature search was performed on April 30, 2015 in data bases of MEDLINE, EMBASE, Scopus and Google Scholar for the terms 'multiple sclerosis', 'incidence', 'prevalence', 'epidemiology', 'migration', 'emigrant', 'immigrant', 'Iran', 'Parsis' and 'Persian'. Study location, prevalence day or period, and age of at disease onset were recorded for all the included publications. Nine publications from Sweden, Canada, Norway, UK, and India were included. Only three reported age-adjusted prevalence and six reported age of disease onset. MS prevalence among Iranian emigrants varied from 21 per 100,000 people in Bombay, India in 1985 to 433 per 100,000 people in British Columbia, Canada in 2012. Five studies reported the prevalence in the region of interest, ranging from 1.33 in Bombay, India to 240 in British Columbia, Canada. Five studies also reported the prevalence of MS in the population of the destination country, and in all of them, the prevalence of MS was higher in Iranian immigrants compared to native people. Prevalence studies performed in Iran and also on Iranian emigrants indicate roles for both genetic and environmental factors in MS susceptibility. Data might indicate that living in a high-risk area increases the susceptibility to MS.

Does lipoic acid consumption affect the cytokine profile in multiple sclerosis patients: a double-blind, placebo-controlled, randomized clinical trial.

BACKGROUND: A limited amount of data exists regarding the effect of lipoic acid (LA), an oral antioxidant supplement, on cytokine profiles among multiple sclerosis (MS) patients. OBJECTIVE: We aimed to assess the effect of daily consumption of LA on the cytokine profiles in MS patients. METHODS: In this double-blind, placebo-controlled, randomized clinical trial, 52 relapsing-remitting MS patients with an age range of 18-50 years were recruited into 2 groups: LA consumption (1,200 mg/day) or placebo. Patients followed their prescribed supplements for 12 weeks. Fasting blood samples for cytokine profile measurement were collected at baseline and after the intervention. Anthropometric parameters were measured based on the standard guidelines. RESULTS: INF-γ, ICAM-1, TGF-ß and IL-4 were significantly reduced in the LA group compared to the placebo group [(INF-γ: 0.82 ± 0.2 vs. 0.2 ± 0.2 pg/ml, p < 0.0001), (ICAM-1: 20.2 ± 9.4 vs. 8 ± 10 ng/ml, p = 0.0001), (TGF-ß: 103.1 ± 20.2 vs. 54.9 ± 26 ng/ml, p < 0.0001) and (IL-4: 0.1 ± 0.1 vs. 1.02 ± 1.7 ng/ml, p = 0.0112)]. No significant changes in TNF-α, IL-6, EDSS and MMP-9 were found between the LA and placebo groups (p = 0.6, p = 0.8, p = 0.09 and p = 0.8, respectively). CONCLUSION: The results suggested that consumption of 1,200 mg LA per day beneficially affects several inflammatory cytokines including INF-γ, ICAM-1 TGF-ß and IL-4. Further investigations are needed to verify the beneficial role of LA on other cytokine profiles among MS patients.

Effect of lipoic acid consumption on oxidative stress among multiple sclerosis patients: a randomized controlled clinical trial.

OBJECTIVES: Multiple sclerosis is a neurodegenerative and demyelinating disease of central nervous system. High levels of oxidative stress are associated with inflammation and play an important role in pathogenesis of multiple sclerosis. This double-blind, randomized controlled clinical study was carried out to determine the effect of daily consumption of lipoic acid on oxidative stress among multiple sclerosis patients. METHODS: A total of 52 relapsing-remitting multiple sclerosis patients, aged 18-50 years with Expanded Disability Status Scale ≤5.5 were assigned to consume either lipoic acid (1200 mg/day) or placebo capsules for 12 weeks. Fasting blood samples were collected before the first dose taken and 12 hours after the last. Dietary intakes were obtained by using 3-day dietary records. RESULTS: Consumption of lipoic acid resulted in a significant improvement of total antioxidant capacity (TAC) in comparison to the placebo group (P = 0.004). Although a significant change of TAC (-1511 mmol/L, P = 0.001) was found within lipoic acid group, other markers of oxidative stress including superoxide dismutase activity, glutathione peroxidase activity, and malondialdehyde levels were not affected by lipoic acid consumption. DISCUSSION: These results suggest that 1200 mg of lipoic acid improves serum TAC among multiple sclerosis patients but does not affect other markers of oxidative stress.

Lifetime physical activity is associated with gut bacteria and brain health in people with multiple sclerosis: Focus on physical activity intensity.

BACKGROUND: Physical activity can improve brain health in people with multiple sclerosis (PwMS). One of the underlying mechanisms can be the modulation of gut bacteria. The association of different intensity of physical activity in a lifetime; and brain volume, lesion volume, and number, and gut bacteria counts were investigated in the current study. METHODS: Forty-five PwMS were recruited, and magnetic resonance imagining was used to evaluate brain volume, lesion volume, and number. Also, stool samples were taken for evaluation faecalibacterium prausnitzii, akkermansia muciniphila, prevotella, and bacteroides count. Moreover, lifetime physical activity was assessed using the adapted version of the historical activity questionnaire. RESULTS: Data revealed a significant association of physical activity with brain volume (r = 0.41), lesion volume (r=-0.35), lesion number (r=-0.37), akkermansia muciniphila (r=-0.34), prevotella (r = 0.52) and bacteroides (r=-0.32) count (p<0.05). Moderate-intensity of physical activity was associated with brain volume (r = 0.33), lesion volume (r=-0.38), prevotella (r = 0.35) and bacteroides (r=-0.40) count (p<0.05). Moreover, vigorous-intensity of physical activity was associated with brain volume (r = 0.38), lesion number (r=-0.39), akkermansia muciniphila (r=-0.30) and prevotella (r = 0.56) count (p<0.05). CONCLUSION: Our results suggest that lifetime physical activity is associated with brain health and gut bacteria count in PwMS. Additionally, the heterogeneity of the association of the physical activity intensities with the studied variables indicates the importance of using different intensities of physical activity to greater benefit from physical activity.

Physicians' opinions on the necessity of COVID-19 vaccination in patients with epilepsy.

The aim of the current study was to investigate the opinions of neurologists and psychiatrists in Iran on the necessity of COVID-19 vaccination in patients with epilepsy (PWE). These data can help policy makers understand the concerns of these healthcare professionals. This was a survey study. On September 1st, 2020 we sent a questionnaire (using Google-forms) to all neurologists and psychiatrists in Iran via WhatsApp. The survey included three general questions (age, sex, and discipline) and six COVID-specific questions. In total, 202 physicians participated in this study (116 neurologists and 86 psychiatrists). Of the participants, 27% believed that PWE are at increased risk of contracting COVID-19. The majority (74%) of the participants would confidently recommend COVID-19 vaccine to their patients. However, only 49% of the physicians would recommend such a vaccine to all patients; others would consider it in special populations only. The overwhelming majority (91%) of the participants would recommend COVID-19 vaccine only when a reliable vaccine becomes available. Many physicians would trust a vaccine that is approved by the World Health Organization (WHO) (46%) or a vaccine that is approved by the Food and Drug Administration (FDA-USA) (34%). Physicians have concerns on the issue of the necessity of (a future) COVID-19 vaccine in PWE. The most important concern is the reliability of a vaccine and in this regard, two health agencies, the WHO and the FDA, are the most trusted organizations to approve a vaccine against COVID-19.

Analysis of HLA DR2&DQ6 (DRB1*1501, DQA1*0102, DQB1*0602) haplotypes in Iranian patients with multiple sclerosis.

Multiple sclerosis (MS) is prototype of inflammatory demyelinating disease of the central nervous system .The etiology of MS remains unclear, but according to current data the disease develops in genetically susceptible individuals and may require additional environmental triggers. The human leukocyte antigen (HLA) class II alleles (DRB1*1501, DQA1*0102, DQB1*0602) may have the strongest genetic effect in MS. In this study, the role of these alleles were investigated in 183 Iranian patients with multiple sclerosis and compared with 100 healthy individuals. HLA typing for DRB1*1501, DQA1*0102, DQB1*0602 was performed by polymerase chain reaction (PCR) amplification with sequence-specific primers (PCR-SSP) method. The results show that, HLA DR B1*1501 was significantly more frequent among MS patients (46% vs. 20%, PV = 0.0006) but DQA1*0102 haplotype was negatively associated with MS (30% vs. 50%, PV = 0.0049) and no significant association was found with DQB1*0602 and MS patients in comparison with control group (24% and 30%, PV = 0.43). No significant correlation was observed among these alleles with sex, type of disease; initial symptoms, expanded disability status scale (EDSS), as well as age at onset and familial MS. This study therefore indicates that there is no association of above HLA haplotypes with clinical presentation, disease duration, and disability in Iranian patients with MS which is in line with other previous studies in different ethnic groups.

Carotid endarterectomy for carotid stenosis in patients selected for coronary artery bypass graft surgery.

BACKGROUND: Carotid stenosis and coronary artery disease can occur simultaneously. In patients with coronary artery disease who are scheduled for coronary artery bypass graft (CABG) surgery, but who also have carotid artery stenosis, there is controversy about the role of carotid surgery. It is not known whether any benefit from prophylactic carotid endarterectomy (by avoiding stroke and neurological dysfunction complicating CABG surgery) outweighs the risks. OBJECTIVES: To assess, in patients undergoing CABG surgery with a carotid stenosis more than 50%, the effects of carotid endarterectomy plus best medical therapy compared with best medical therapy alone on the overall risk of major clinical outcomes including death, stroke, and myocardial infarction. SEARCH STRATEGY: We searched the trials registers of the Cochrane Stroke Group (searched October 2008) and the Cochrane Heart Group (searched November 2008). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2008), MEDLINE (1966 to November 2008), EMBASE (1980 to November 2008), reference lists of identified trials, and ongoing trials and research registers (last searched November 2008). SELECTION CRITERIA: We planned to include all truly randomised controlled trials comparing carotid endarterectomy plus best medical therapy with best medical therapy alone in patients selected for CABG surgery. The main outcome was perioperative death. DATA COLLECTION AND ANALYSIS: We planned for two review authors to independently assess the methodological quality of included studies, and extract data. MAIN RESULTS: We did not find any eligible studies. AUTHORS' CONCLUSIONS: We found no evidence from randomised trials by which to assess the benefits and risks of prophylactic carotid surgery before CABG surgery. Randomised controlled trials are required to reliably document the risks and benefits of such procedures.

Efficacy and safety of natalizumab extended interval dosing.

OBJECTIVE: It is postulated that extending the dosing interval of natalizumab (NTZ) from 4 to 5-8 weeks might decrease the risk of progressive multifocal leukoencephalopathy (PML). The aim of this study was to assess the effect of extended interval dosing (EID) on the therapeutic efficacy of natalizumab. METHODS: We reviewed 85 patients treated at two MS centers in the Middle East with natalizumab for at least 6 months using EID. Patients were shifted after an initial treatment period at standard interval dosing (SID) to an EID ranging from 5-8 weeks. RESULTS: The mean treatment duration on SID and EID was 15.4 ±â€¯11.9 and 11.8 ±â€¯7.0 months, respectively. By the end of SID and EID treatment 95.3% and 93.9% of patients were free of relapses (P = 0.41) with an annualized relapse rate (ARR) of 0.0006 and 0.001 respectively (P = 0.42). The mean EDSS at the end of SID and EID periods was 2.56 ±â€¯1.62 and 2.59 ±â€¯1.61 respectively (P = 0.84). A total of 97.6% and 94.7% of patients had no enhancing lesions on MRI during the SID and EID periods respectively (P = 0.18). There were no cases of PML and the rate of infections was lower during the EID period. CONCLUSION: In patients treated with natalizumab, shifting from SID to EID has no negative effect on efficacy as evidenced by relapse rate, disability progression and MRI activity.

The thalamus and multiple sclerosis: modern views on pathologic, imaging, and clinical aspects.

The paired thalamic nuclei are gray matter (GM) structures on both sides of the third ventricle that play major roles in cortical activation, relaying sensory information to the higher cortical centers that influence cognition. Multiple sclerosis (MS) is an immune-mediated disease of the human CNS that affects both the white matter (WM) and GM. A number of clinical observations as well as recent neuropathologic and neuroimaging studies have clearly demonstrated extensive involvement of the thalamus, basal ganglia, and neocortex in patients with MS. Modern MRI techniques permit visualization of GM lesions and measurement of atrophy. These contemporary methods have fundamentally altered our understanding of the pathophysiologic nature of MS. Evidence confirms the contention that GM injury can be detected in the earliest phases of MS, and that iron deposition and atrophy of deep gray nuclei are closely related to the magnitude of inflammation. Extensive involvement of GM, and particularly of the thalamus, is associated with a wide range of clinical manifestations including cognitive decline, motor deficits, fatigue, painful syndromes, and ocular motility disturbances in patients with MS. In this review, we characterize the neuropathologic, neuroimaging, and clinical features of thalamic involvement in MS. Further, we underscore the contention that neuropathologic and neuroimaging correlative investigations of thalamic derangements in MS may elucidate not heretofore considered pathobiological underpinnings germane to understanding the ontogeny, magnitude, and progression of the disease process.