Therapeutic Plasma Exchange (TPE) Complications in Patients With Multiple Sclerosis (MS) and Clinically Isolated Syndrome (CIS): A Report From a Tertiary Center.

BACKGROUND: Therapeutic plasma exchange (TPE) is a conventional second-line treatment for patients with multiple sclerosis (MS) or clinically isolated syndrome with steroid-refractory relapses. METHODS: MS and clinically isolated syndrome patients with a steroid-refractory relapse, who fulfilled the indications for TPE were enrolled in this study. An expert nurse recorded the data comprising age, sex, type of MS, disease modifying therapy, disease duration, relapse rate, vital signs at the beginning, during and at the end of each plasma exchange session, plasma exchange volume, normal saline volume, and TPE complications. Ultimately, the statistical association was estimated amongst the variables. RESULTS: A total of 122 cases were assessed. Twelve cases (9.8%) received plasmapheresis for the second time. The mean age was 32.2±8.7 years and 107 (87.7%) were female. In total, 609 plasma exchange sessions were completed. Hypotension and skin reaction were the most clinical complications. Hemoglobin loss and hypokalemia were the most laboratory complications. Fifty-four cases (44.3%) had no complications, 40 (32.8%) had 1 complication, 21 (17.2%) 2 complications, 6 (4.9%) had 3 complications, and 1 (0.8%) disclosed 4 complications. The relapse rate in the past 12 months and the mean plasma volume exchange were significantly different between the groups. CONCLUSIONS: We revealed that TPE could be considered as a safe second-line therapy in MS relapses. Hypotension, skin reaction, hemoglobin loss, and hypokalemia were the most complications of TPE in our patients.

Changes in DNA methylation in APOE and ACKR3 genes in multiple sclerosis patients and the relationship with their heavy metal blood levels.

Multiple sclerosis (MS) is a chronic inflammatory disease with demyelinated lesions in the central nervous system caused by genetic and environmental factors. DNA methylation as an epigenetic change influenced by environmental factors, including heavy metals has been implemented in MS disease. We investigated the correlation of DNA methylation changes in APOE and ACKR3 genes in MS patients and the possible association with blood concentration of arsenic (As), cadmium (Cd) and lead (Pb) as major heavy metal pollutants. This study included 69 relapsing-remitting multiple sclerosis (RR-MS) patients and 69 age/gender-matched healthy subjects. The HRM real-time PCR method was used to investigate the changes in DNA methylation and heavy metal concentrations were measured by electrothermal atomic absorption spectrometry. Our results showed that the methylation pattern in the ACKR3 gene of the patient group was more hypomethylated, while in the case of the APOE gene, this pattern was more towards hypermethylation compared to healthy subjects. Moreover, the blood levels of As and Cd metals, but not Pb, were significantly higher in the patient group compare to the control group (p ≤ 0.05). The data indicate that the increase in expression of ACKR3 gene by hypomethylation and the decrease in expression of APOE gene via hypermethylation are possibly involved in the onset and progression of inflammatory processes in MS patients. The level of As can also lead to hypomethylation by disrupting the methylation patterns of the ACKR3 gene, resulting in increased expression in MS patients. Finally, we have shown that epigenetic changes can be an important factor in increasing and decreasing the expression of genes involved in the onset and/or progression of inflammatory processes in MS. Furthermore, exposure to heavy metals, especially As, by changing the natural patterns of DNA methylation can be effective in this disease.

Prevalence of Multiple Sclerosis (MS) in Zanjan Province of Iran.

BACKGROUND: The prevalence of multiple sclerosis (MS) varies in different geographical regions and has dramatically increased in Iran. Revealing the high prevalence rate draws the attention of policymakers and helps them allocate necessary resources. The aim of this study is to determine the prevalence of MS in Zanjan province of Iran. METHODS: We included all registered residents of Zanjan province with MS on the prevalence day (July 31, 2019). All cases met the McDonald criteria. All registered cases in Zanjan MS society were identified as index cases. Data regarding patient's national code, gender, age, age at the first symptom onset, city of residence, marital status, education level, occupation, ethnicity, family history of MS and the time span between symptom's onset and disease diagnosis were recorded. RESULTS: We identified 758 patients, 551 of whom (72.7%) were female. The mean age at the first symptom onset was 28.9 ±8.7 years old. The crude prevalence was 71.6 per 100,000 population (95% CI 66.6-76.9). The disease was most prevalent in Zanjan city (100.5 per 100,000). The gender-specific prevalence per 100,000 population was 105.4 for women (95% CI: 96.8-114.6) and 38.7 for men (95% CI: 33.6-44.1), with female to male ratio of 2.6. The standardized mortality ratio (SMR) was calculated as expected/observed for both men and women as 2.3 (207/88.2) (551/234.1). CONCLUSIONS: Our data confirm that the MS prevalence rate is high in Zanjan province of Iran.

Correlation between heavy metal exposure and GSTM1 polymorphism in Iranian multiple sclerosis patients.

Multiple sclerosis (MS) is an immune-mediated chronic inflammatory disease of the central nervous system. Various exposures to heavy metals can lead to toxicity and oxidative stress. While glutathione-S-transferases are known as oxidative stress-related genes and involved in metal biotransformation. The aim of the present study is to investigate the correlation of GSTM1 polymorphism in MS patients and the possible association with blood concentration of arsenic (As) and cadmium (Cd) as major heavy metal pollutants. This study included 69 relapsing-remitting multiple sclerosis patients and 74 age/gender-matched healthy subjects. The genetic profile was analyzed by PCR, and heavy metal concentrations were measured by electrothermal atomic absorption spectrometry. Our results demonstrated that patients with the GSTM1 null genotype had considerably lower age of onset. However, the frequency of the GSTM1 null genotype was not significantly different between MS and control groups. In addition, the blood As and Cd concentrations were considerably higher in MS patients in comparison with healthy individuals. Also, it revealed that the GSTM1 null genotype associated with high Cd level in MS patients. There was also a trend toward an increase in As level in MS patients. These data may point to susceptibility to cadmium toxicity especially in RR-MS patients with smoking habit. Furthermore, the M1 null genotype will help in a prognosis of MS considering the age of onset. It confirms that the long-term prognosis in MS and patient's disability are influenced by their ability to remove the toxic products and perhaps to decrease oxidative stress.

The role of the cerebellum in multiple sclerosis.

In multiple sclerosis (MS), cerebellar signs and symptoms as well as cognitive dysfunction are frequent and contribute to clinical disability with only poor response to symptomatic treatment. The current consensus paper highlights the broad range of clinical signs and symptoms of MS patients, which relate to cerebellar dysfunction. There is considerable evidence of cerebellar involvement in MS based on clinical, histopathological as well as structural and functional magnetic resonance imaging (MRI) studies. The review of the recent literature, however, also demonstrates a high variability of results. These discrepancies are, at least partially, caused by the use of different techniques and substantial heterogeneity among the patient cohorts in terms of disease duration, number of patients, and progressive vs. relapsing disease courses. Moreover, the majority of studies were cross-sectional, providing little insight into the dynamics of cerebellar involvement in MS. Some links between the histopathological changes, the structural and functional abnormalities as captured by MRI, cerebellar dysfunction, and the clinical consequences are starting to emerge and warrant further study. A consensus is formed that this line of research will benefit from advances in neuroimaging techniques that allow to trace cerebellar involvement at higher resolution. Using a prospective study design, multimodal high-resolution cerebellar imaging is highly promising, particularly in patients who present with radiologically or clinically isolated syndromes or newly diagnosed MS.

Future of management of multiple sclerosis in the middle East: a consensus view from specialists in ten countries.

The prevalence of multiple sclerosis (MS) is now considered to be medium-to-high in the Middle East and is rising, particularly among women. While the characteristics of the disease and the response of patients to disease-modifying therapies are generally comparable between the Middle East and other areas, significant barriers to achieving optimal care for MS exist in these developing nations. A group of physicians involved in the management of MS in ten Middle Eastern countries met to consider the future of MS care in the region, using a structured process to reach a consensus. Six key priorities were identified: early diagnosis and management of MS, the provision of multidisciplinary MS centres, patient engagement and better communication with stakeholders, regulatory body education and reimbursement, a commitment to research, and more therapy options with better benefit-to-risk ratios. The experts distilled these priorities into a single vision statement: "Optimization of patient-centred multidisciplinary strategies to improve the quality of life of people with MS." These core principles will contribute to the development of a broader consensus on the future of care for MS in the Middle East.

Superparamagnetic iron oxide nanoparticles: promises for diagnosis and treatment of multiple sclerosis.

Smart superparamagnetic iron oxide nanoparticles (SPIONs) are the most promising candidate for theragnosis (i.e., diagnosis and treatment) of multiple sclerosis. A deep understanding of the dynamics of the in vivo neuropathology of multiple sclerosis can be achieved by improving the efficiency of various medical techniques (e.g., positron emission tomography and magnetic resonance imaging) using multimodal SPIONs. In this Review, recent advances and challenges in the development of smart SPIONs for theragnostic applications are comprehensively described. In addition, critical outlines of emerging developments are provided from the points of view of both clinicians and nanotechnologists.

Serum prolactin level in patients with multiple sclerosis: a case control study.

BACKGROUND: Multiple sclerosis (MS) is the most common demyelinating disorder of the central nervous system and is considered to be multifactorial with an autoimmune component. Prolactin (PRL) is a neuroendocrine peptide with potent immunomodulatory properties. Hyperprolactinemia enhances several autoimmune disorders and may play a role in the pathogenesis of MS. The aim of this study was to compare serum PRL levels in MS patients with those of healthy controls. MATERIAL/METHODS: There were 43 patients with definite MS and 43 sex- and age-matched healthy controls. Conditions leading to a rise in PRL, such as pregnancy, lactation, and specific underlying diseases and drugs, were excluded. PRL levels were measured in fasting blood samples. For the MS group, disease duration and subtype, clinical manifestations, and expanded disability status scores (EDSS) were also recorded. RESULTS: There were no significant differences in serum PRL levels between the case and control groups in both women and men (376.78+/-231.11 mIU/l in female patients with MS vs. 364.19+/-202.55 mIU/l in female controls, 266.00+/-200.83 mIU/l in male patients with MS vs. 197.25+/-65.25 mIU/l in male controls). We also found no significant relationship between PRL and disease activity, disease duration, and EDSS. CONCLUSIONS: Our findings do not support the hypothesis that MS patients are in a hyperprolactinemic state. However, further studies in more homogenous MS subgroups are needed.