Multiple Sclerosis Exacerbations Research Articles

The prevalence of bruxism and related factors in patients with multiple sclerosis: a comparative study.

To determine the prevalence of bruxism and related factors in patients with multiple sclerosis (MS). Diagnosed with relapsing-remitting MS under the 2010-revised McDonald diagnostic criteria, 182 patients without MS exacerbations during the previous three months were included in the patient group, and 145 healthy individuals made up the control group in the study. Demographic data of the participants in both groups were determined. In the patient and control groups, the diagnosis of definite bruxism was made using the International Classification of Sleep Disorders (Diagnosis and Coding Manual, Second Edition). Bruxism was found in 29.7% (n = 54) of the patients and in 12.4% (n = 18) of the controls, and the difference was statistically significant (p < 0.001). Of all patients, the onset of bruxism was found in 70.4% (n = 38) after the diagnosis and in 29.6% (n = 169) prior to the diagnosis of MS. Compared with those without bruxism, the mean age (p = 0.031) and the score of the Expanded Disability Status Scale (p = 0.001) were also significantly higher among MS patients with bruxism. Between MS patients with and without bruxism, no significant differences were found in terms of sex, marital status, educational status, employment, cigarette smoking, total number of exacerbations, number of exacerbations within the previous year, and drugs used. The frequency of bruxism was found to be higher in the patients with MS than in the controls. Bruxism is associated with age and the Expanded Disability Status Scale score in MS patients.

Belly-born B cells bathe the brain.

IgA-expressing antibody secreting cells that are formed in the gut travel to the brain to diminish inflammation during multiple sclerosis exacerbations.

A myeloid cell atlas of neuroinflammation

Neuroimmunology Myeloid cells, such as dendritic cells and macrophages, in the central nervous system (CNS) play critical roles in the initiation and exacerbation of multiple sclerosis (MS). Jordao et al. combined high-throughput single-cell RNA sequencing and intravital microscopy to compile a transcriptional atlas of myeloid subsets in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Microglia and other CNS-associated macrophages expanded and transformed into various context-dependent subtypes during EAE. Furthermore, dendritic cells and monocyte-derived cells, but not resident macrophages, played a critical role by presenting antigen to pathogenic T cells. This exhaustive characterization may inform future therapeutic targeting strategies in MS. Science , this issue p. [eaat7554][1] [1]: /lookup/doi/10.1126/science.aat7554

Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation.

The innate immune cell compartment is highly diverse in the healthy central nervous system (CNS), including parenchymal and non-parenchymal macrophages. However, this complexity is increased in inflammatory settings by the recruitment of circulating myeloid cells. It is unclear which disease-specific myeloid subsets exist and what their transcriptional profiles and dynamics during CNS pathology are. Combining deep single-cell transcriptome analysis, fate mapping, in vivo imaging, clonal analysis, and transgenic mouse lines, we comprehensively characterized unappreciated myeloid subsets in several CNS compartments during neuroinflammation. During inflammation, CNS macrophage subsets undergo self-renewal, and random proliferation shifts toward clonal expansion. Last, functional studies demonstrated that endogenous CNS tissue macrophages are redundant for antigen presentation. Our results highlight myeloid cell diversity and provide insights into the brain's innate immune system.

Peripheral viral challenge exacerbates experimental autoimmune encephalomyelitis.

Peripheral viral infections are potent triggers of exacerbation in multiple sclerosis (MS). Here, we used a preclinical model of MS, the experimental autoimmune encephalomyelitis (EAE) to corroborate this comorbidity in an experimental setting. EAE was induced by immunization of mice with MOG peptide, and paralysis was scored using a 5-point scale. At the onset of the chronic phase of the disease (Days 42-58 after MOG injection) the animals were divided into low responders (LR) and high responders (HR) with the mean score of 1.5 and 2.5, respectively. The acute phase response (APR) was induced by intraperitoneal injections of a viral mimetic, polyinosinic-polycytidylic acid (PIC). Two daily injections were performed on Days 42 and 44 (PIC42,44 challenge) and on Days 54, 55 and 56 (PIC54,55,56 challenge). PIC42,44 challenge had no effect of EAE disease, whereas PIC54,55,56 challenge rapidly increased paralysis but only in HR group. This exacerbation ultimately led to animal death by Day 58. These results demonstrate that antiviral APR is a potent exacerbator of EAE, and that this activity directly correlates with the severity of the disease. This in turn, indicates that antiviral APR might play a pivot role in linking peripheral viral infections with MS exacerbations.

Comparative characteristic of laboratory indicators for encephalitis, disseminated encephalomyelitis and multiple sclerosis in children

Background. The similarity of the clinical manifestations of encephalitis (E), disseminated encephalomyelitis (DEM) and multiple sclerosis (MS) in children, the complexity of predicting the nature of the course and outcome of diseases determines the search for additional diagnostic and prognosis criteria.Objective: a comparative characteristic of laboratory indicators for E, DEM and RS in children to assess their diagnostic and prognostic value.Materials and methods. Fifty six children (14 children with E, 14 – with DEM, 28 – with MS) and 16 children of the control group (with acute respiratory virus infection) at the age from 10 to 17 years were examined. Laboratory methods included standard studies of cerebrospinal fluid (protein, cytosis), determination of concentrations of albumin and immunoglobulin G (IgG) in cerebrospinal fluid and serum with subsequent calculation of protein indices (albumin, immunoglobulin, intrathecal immunoglobulin G indexes).Results. With all nosological forms in the serum there were no significant differences between albumin and IgG from the control group, whereas in the cerebrospinal fluid an excess of the concentration of IgG was detected at a normal level of albumin. An increase in the albumin index was found only in E, whereas the immunoglobulin index was significantly higher than the norm in all groups of patients. A significant spread of the intrathecal IgG index (from 0.1 to 11.9) was found, which determined the analysis of clinical and laboratory parameters by subgroups, depending on its magnitude. The maximum incidence of increased intrathecal IgG synthesis was detected in children with MS (with exacerbation of MS – 74 %, in remission – 67 %), whereas in E and DEM, an increase was observed in about half of the patients surveyed and associated with a more favorable course of the disease.Conclusion. The data obtained make it possible to assert that, despite the commonness of some pathogenetic mechanisms, there are differences in the degree of impaired permeability of the blood brain barrier, the intensity of the systemic and intrathecal humoral immune response in E, DEM and RS, which may determine the features of their course and the outcome of the disease, including the transformation of the DEM in the RS.

Contemporary Algorithms for the Diagnosis and Treatment of Multiple Sclerosis Based on Individual Assessment of Patients’ Status

This review describes current views on the diagnosis of multiple sclerosis (MS), the treatment of exacerbations of MS, and the use of MS disease-modifying drugs. Algorithms for diagnosis and treatment are provided. Particular attention is paid to analysis of the efficacy, tolerance, and safety of contemporary drugs for the treatment of MS.

Rapid Improvement of Symptoms after Fibrinolysis in a Patient with Multiple Sclerosis Exacerbation (P3.405)

Rapid Improvement of Symptoms after Fibrinolysis in a Patient with Multiple Sclerosis Exacerbation (P3.405)

ОСОБЕННОСТИ РЕПРОДУКТИВНОГО ЗДОРОВЬЯ ЖЕНЩИН, БОЛЬНЫХ РАССЕЯННЫМ СКЛЕРОЗОМ

Introduction. The incidence of multiple sclerosis (MS) is two times higher in women, and the debut of the disease falls on young reproductive age, which makes the problem urgent. Purpose: to assess the characteristics of the reproductive health of women with MS in different age periods. Material and methods. A prospective study was carried out in parallel groups and a case-control study of women of early and late reproductive age with a reliable diagnosis of MS. Results. During pregnancy, there was a significant decrease in the frequency of exacerbations of MS in comparison with the pre-gravity period; voluntary infertility and childlessness is registered in 21.3 % and 32 % of women, respectively. An increase in the concentration of follicle stimulating hormone (FSH) means an increase in the degree of disability on the Expanded Disability Status Scale (EDSS) and the duration of the disease. The decrease in the concentration of dehydroepiandrosterone sulfate (DHEA-S) corresponds to a higher degree of disability on the EDSS scale and the duration of the disease. Conclusion. Pregnancy has a protective effect on the clinical course of MS. Infertility in most cases is voluntary, but at the same time hypergonadotropic condition and hypoandrogenia are observed in women with MS already in the early reproductive age, which interferes with the steroid synthetic function of the ovaries and can cause impaired fertility.

Stereotactic Radiosurgery for Trigeminal Neuralgia in Patients with Multiple Sclerosis: A Multicenter Study

Facial pain response to various surgical interventions in patients with multiple sclerosis (MS)-related trigeminal neuralgia (TN) is considered much less favorable than for typical TN. No large patient series has been published regarding stereotactic radiosurgery (SRS), the least invasive treatment modality for MS patients with medically refractory TN. This is a multicenter retrospective study investigating the clinical outcomes following SRS for patients with MS-related TN. A total of 263 patients contributed by nine member institutions of the International Gamma Knife Research Consortium (IGKRF) constituted this study. The median age at the time of SRS was 57 years (range, 31 to 90 years). Eighty-seven patients (33%) had undergone various surgical procedures prior to SRS. The median latency period of pain response after SRS was one month (range, 1 day to 14.1 months). Reasonable pain control (BNI Pain Scores I-IIIb) was achieved in 232 patients (88.2%). The median maintenance period from SRS was 14.1 months (range, 10 days to 10 years). The actuarial reasonable pain control maintenance rate at 1 year, 2 years, and 4 years was 54%, 35%, and 24%, respectively. There was a statistically significant correlation between the status of achieving BNI-I and the maintenance of facial pain recurrence-free rate. The median recurrence-free rate was 36 months and 12.2 months in patients achieving BNI-I and those of BNI greater than I, respectively (log rank test, P = 0.046). A negative correlation between the time interval from the last initiation of MS exacerbation to the first SRS and possibility of reaching BNI-I was identified (P = 0.002, OR = 1.99, 95% CI, 1.30 to 3.12). Among 210 patients with known status of post-SRS complications, the new-onset of facial numbness (BNI-I or II) after SRS occurred in 21 patients (10%). In the largest series investigating the efficacy and safety of MS-related TN treated SRS, this approach offers a reasonable benefit to risk profile for patients who have exhausted medical management. More favorable initial response to SRS may predict a long-lasting pain control. Earlier treatment with SRS in the presence of MS relapse may lead to an increasing rate of achieving BNI-I facial pain relief.

Lymphocytes in the treatment with interferon beta-1 b

BackgroundMultiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease affecting the central nervous system. One of the basic medications for the treatment of a clinically isolated syndrome (CIS) or relapsing-remitting MS is interferon beta (INFβ). Although the exact mechanism of its effects is unknown, the medication has an anti-inflammatory and immunomodulatory effect. The goal of this study was to determine the characters which are affected in patients treated with INFβ. MethodsA total of 97 patients (25 males and 72 females) were included into the study. Patients were treated by INFβ 1-b (subcutaneous injection, 250µg, each other day). Clinical evaluations were performed by an attending neurologist. Peripheral blood samples were obtained just prior to treatment and 5 years after INFβ 1-b. Statistical analysis and processing of the obtained data were performed by using a comprehensive statistical software package MATLAB®. ResultsA significant decrease of the observed parameters after 5 years’ of treatment (significant at the 1% significance level) was found in the absolute and relative CD69 count, absolute cytotoxic/suppressor T lymphocyte count, absolute total leukocyte count, absolute natural killer cells count. A significant decrease of the observed parameters after 5 years’ of treatment (significant at the 5% significance level) was found in the absolute lymphocyte count, relative cytotoxic/suppressor T lymphocyte count, relative CD3+CD69+ count and absolute CD8+CD38+ count. ConclusionThe treatment with interferon beta reduces clinical exacerbations in multiple sclerosis (MS) through several known immunomodulatory mechanisms. However, the exact mechanism of effect of this medication is not known. This study presents some parameters that were affected by the long-term INFβ treatment.

Safety and efficacy of dual-lead thalamic deep brain stimulation for patients with treatment-refractory multiple sclerosis tremor: a single-centre, randomised, single-blind, pilot trial

Efficacy in previous studies of surgical treatments of refractory multiple sclerosis tremor using lesioning or deep brain stimulation (DBS) has been variable. The aim of this study was to investigate the safety and efficacy of dual-lead thalamic DBS (one targeting the ventralis intermedius-ventralis oralis posterior nucleus border [the VIM lead] and one targeting the ventralis oralis anterior-ventralis oralis posterior border [the VO lead]) for the treatment of multiple sclerosis tremor. We did a single centre, single-blind, prospective, randomised pilot trial at the University of Florida Center for Movement Disorders and Neurorestoration clinic (Gainesville, FL, USA). We recruited adult patients with a clinical diagnosis of multiple sclerosis tremor refractory to previous medical therapy. Before surgery to implant both leads, we randomly assigned patients (1:1) to receive 3 months of optimised single-lead DBS-either VIM or VO. We did the randomisation with a computer-generated sequence, using three blocks of four patients, and independent members of the Center did the assignment. Patients and all clinicians other than the DBS programming nurse were masked to the choice of lead. Patients underwent surgery 1 month after their baseline visit for implantation of the dual lead DBS system. A pulse generator and two extension cables were implanted in a second surgery 3-4 weeks later. Patients then received an initial 3-month period of continuous stimulation of either the VIM or VO lead followed by blinded safety assessment of their tremor with the Tolosa-Fahn-Marin Tremor Rating Scale (TRS) during optimised VIM or VO lead stimulation at the end of the 3 months. After this visit, both leads were activated in all patients for an additional 3 months, and optimally programmed during serial visits as dictated by a prespecified programming algorithm. At the 6-month follow-up visit, TRS score was measured, and mood and psychological batteries were administered under four stimulation conditions: VIM on, VO on, both on, and both off (the order of testing was chosen by a computer-generated random sequence, assigned by independent members of the centre, and enacted by an unmasked DBS programming nurse). Each of four stimulation settings were tested over 4 consecutive days, with stimulation settings held constant for at least 12 h before testing. The primary outcome was change in mean total TRS score at the 6-month postoperative assessment with both leads activated, compared with the preoperative baseline mean TRS score. Analysis was by intention to treat. Safety was analysed in all patients who received the surgical implantation except in one patient who discontinued before the safety assessment. This trial is registered with ClinicalTrials.gov, number NCT00954421. Between Jan 16, 2007, and Dec 17, 2013, we enrolled 12 patients who were randomly assigned either to 3 initial months of VIM-only or VO-only stimulation. One patient from the VO-only group developed an infection necessitating DBS explantation, and was excluded from the assessment of the primary outcome. Compared with the mean baseline TRS score of 57·0 (SD 10·2), the mean score at 6 months decreased to 40·1 (17·6), -29·6% reduction; t=-0·28, p=0·03. Three of 11 patients did not respond to surgical intervention. One patient died suddenly 2 years after surgery, but this was judged to be unrelated to DBS implantation. Serious adverse events included a superficial wound infection in one patient that resolved with antibiotic therapy, and transient altered mental status and late multiple sclerosis exacerbation in another patient. The most common non-serious adverse events were headache and fatigue. Dual lead thalamic DBS might be a safe and effective option for improving severe, refractory multiple sclerosis tremor. Larger studies are necessary to show whether this technique is widely applicable, safe in the long-term, and effective in treating multiple sclerosis tremor or other severe tremor disorders. US National Institutes of Health, the Cathy Donnellan, Albert E Einstein, and Birdie W Einstein Fund, and the William Merz Professorship.

Multipl sklerozda femur başı avasküler nekrozu

Objective: Corticosteroid (CS) therapy is widely used as the standard treatment for acute exacerbations of multiple sclerosis (MS). Avascular necrosis (AVN) of the femoral head is one of the long–term complications related to CS therapy. Our study aims to investigate the association between annual and cumulative doses of CS treatment and radiographic assessment of AVN of the femoral head in MS. Material and Methods: One patient group and two control groups were formed. The study group consisted 60 MS cases treated with intravenous methylprednisolone (IVMP) and the 2 control groups consisted 22 MS patients (Control I) without CS treatment and 25 healthy controls (Control II). Sixty patients who underwent CS treatment were divided into 3 subgroups of 20 cases each, treated with either IVMP only, IVMP and interferon, and IVMP and glatiramer acetate (GA). Neurological examinations and demographic data of all cases were recorded. The presence of AVN of femoral head in patient and control groups was evaluated using magnetic resonance imaging and Ficat staging system. Results: Avascular necrosis (AVN) of femoral head was observed in 4 (6.7%) MS patients who were treated with CS. The mean annual CS dose was 8.07 g and mean cumulative dose was 31 gr. There was a significant but no statistical difference, in annual and cumulative IVMP doses between patients who have and don’t have AVN of femoral head (p=0.085 and p=0.246, respectively). Conclusion: Our all data support the idea that annual dose of CS may increase AVN of femoral head development in MS patients. It is important to evaluate the CS-treated MS patients with MRI in this respect, due to the possible treatment of early-stage AVN of femoral head.

Sleep Disorder as a Triggering Factor for Relapse in Multiple Sclerosis

Background/Aims: To determine the effect of sleep disturbances on predisposing multiple sclerosis (MS) patients for acute relapse. Methods: This case-control study was conducted on 80 MS patients including 40 patients in the remission phase and 40 in the relapse phase. Patients were asked to fill in the Pittsburgh Sleep Quality Index to determine their sleep quality during the previous month. Individuals with scores of 5 or less were considered having normal sleep quality. Results: Mean ± SD ages were 32.5 ± 7.7 and 30.2 ± 7.2 years among patients with and without acute relapses, respectively (p > 0.05). The mean disease duration and disease severity (according to Expanded Disability Status Scale [EDSS]) were comparable across the groups (p > 0.05). Among those with and without acute exacerbations, 87.5 and 50% had poor sleep quality, respectively (p = 0.0001), with OR of 1.75 (95% CI 1.25-2.43). The age, gender, EDSS, and disease duration did not associate with sleep quality in either groups (p > 0.05). Conclusions: This study showed that sleep disturbance might be a trigger for an acute MS exacerbation. Increasing the awareness of specialists and routine screening of sleep disorders in MS patients are warranted, as treatment of these disorders might decrease the likelihood of acute relapses.

The Skin-Brain Connection Hypothesis, Bringing Together CCL27-Mediated T-Cell Activation in the Skin and Neural Cell Damage in the Adult Brain.

Recent discovery of an association of low serum melatonin levels with relapse in multiple sclerosis (MS) opens a new horizon in understanding the pathogenesis of this disease. Skin is the main organ for sensing seasonal changes in duration of sunlight exposure. Level of melatonin production is dependent on light exposure. The molecular mechanisms connecting peripheral (skin) sensing of the light exposure and developing brain inflammation (MS) have not been investigated. We hypothesize that there is a connection between the reaction of skin to seasonal changes in sunlight exposure and the risk of MS and that seasonal changes in light exposure cause peripheral (skin) inflammation, the production of cytokines, and the subsequent inflammation of the brain. In skin of genetically predisposed individuals, cytokines attract memory cutaneous lymphocyte-associated antigen (CLA+) T lymphocytes, which then maintain local inflammation. Once inflammation is resolved, CLA+ lymphocytes return to the circulation, some of which eventually migrate to the brain. Once in the brain these lymphocytes may initiate an inflammatory response. Our observation of increased CC chemokine ligand 27 (CCL27) in MS sera supports the involvement of skin in the pathogenesis of MS. Further, the importance of our data is that CCL27 is a chemokine released by activated keratinocytes, which is upregulated in inflamed skin. We propose that high serum levels of CCL27 in MS are the result of skin inflammation due to exposure to seasonal changes in the sunlight. Future studies will determine whether CCL27 serum level correlates with seasonal changes in sunlight exposure, MS exacerbation, and skin inflammation.

Combination aquatic and land physical therapy program improved function and reduced spasticity after acute illness and exacerbation of multiple sclerosis: A case report

Combination aquatic and land physical therapy program improved function and reduced spasticity after acute illness and exacerbation of multiple sclerosis: A case report

Suicide Attempts Following Fingolimod use in Patients with Relapsing Multiple Sclerosis: Is there a possible link?

Fingolimod is the first oral therapy approved for reducing exacerbations in Multiple Sclerosis (MS). It is widely accepted that different preparations of beta interferons may aggravate depression and trigger suicide in MS patients and that the drugs should be stopped immediately following the suicidal idea. The association between newly approved drugs such as Fingolimod and Natalizumab with depression and suicidality is not clear. Here, we report three patients with relapsing MS, who committed suicide while receiving Fingolimod. Although the link between suicide and Fingolimod is not clear, but practicing physicians need to be aware of this possible adverse event. It is also important to evaluate the psychological status of the patients not only in patients receiving beta interferons, but also patients who are treated with newly approved drugs.

Аnalysis of risk factors in patients with multiple sclerosis in terms of comorbidity

Were analyzed risk factors (RF) in patients with multiple sclerosis (MS) in the aspect of comorbidity. It was systematized and analyzed anamnestic RF and the development of MS. It is shown that multifactorial pathological effects is most important as a factor of development of the disease, exacerbation and progression in MS. Along with such traditional RF of MS, as a viral infection, psycho-emotional stress, and childbirth, the development of disease exacerbation and progression in MS also have an important role such RF as sleep disturbances, exacerbation of visceral disease and exacerbation of pain.

Influenza virus infection exacerbates experimental autoimmune encephalomyelitis disease by promoting type I T cells infiltration into central nervous system

Multiple sclerosis starts with increased migration of auto-reactive lymphocytes across the blood-brain barrier, resulting in persistent neurodegeneration. Clinical and epidemiological studies indicated upper respiratory viral infections are associated with clinical exacerbation of multiple sclerosis. However, so far there is no any direct evidence to support it. Using the experimental autoimmune encephalomyelitis mice as the model for multiple sclerosis, we demonstrated that mice experienced with influenza virus infection were unable to recover from experimental autoimmune encephalomyelitis with a long-term exacerbation. The exacerbated disease was due to more type I T cells, such as CD45highCD4+CD44high, CD45highCD4+CCR5+, CD45high IFNγ+CD4+, MOG35-55-specific IFNγ+CD4+ and influenza virus-specific IFNγ+CD4+ T cells, infiltrating central nervous system in mice with prior influenza virus infection. Influenza virus infection created a notable inflammatory environment in lung and mediastinal lymph node after influenza virus inoculation, suggesting the lung may constitute an inflammatory niche in which auto-aggressive T cells gain the capacity to enter CNS. Indeed, the early stage of EAE disease was accompanied by increased CCR5+CD4+, CXCR3+CD4+ T cell and MOG35-55 specific CD4+ T cells localized in the lung in influenza virus-infected mice. CCL5/CCR5 might mediate the infiltration of type I T cells into CNS during the disease development after influenza infection. Administration of CCR5 antagonist could significantly attenuate the exacerbated disease. Our study provided the evidence that the prior influenza virus infection may promote the type I T cells infiltration into the CNS, and subsequently cause a long-term exacerbation of experimental autoimmune encephalomyelitis.

Risk of venous thromboembolism in neuromyelitis optica patients hospitalized for acute relapse

Background: Neuromyelitis optica spectrum disorder (NMOSD) patients may be at increased risk of venous thromboembolism (VTE) not only due to ambulatory disability but also due to systemic autoimmune and inflammatory mechanisms altering the hemostatic balance. Objective: To compare the risk of VTE in NMOSD versus multiple sclerosis (MS) patients hospitalized for acute relapses. Methods: Hospital admissions for MS or NMOSD exacerbations were retrospectively identified. Demographics and medical history were recorded. The relationship between visit diagnosis and presence of VTE within 6 weeks of relapse onset was assessed by univariate logistic regression. A multivariate model evaluated the relationship between diagnosis, age, race, gender, body mass index (BMI), disease modifying therapy use, oral corticosteroid use, oral contraceptive use, smoking, length of stay (LOS), and ambulatory status on VTE risk. Results: A total of 30 NMOSD patients had 55 hospitalizations; 179 MS patients had 264 hospitalizations. Six NMOSD patients and one MS patient had VTE. NMOSD visits compared to MS visits had an odds ratio (OR) of VTE of 32.2 (p = 0.002). NMOSD was more likely to be associated with VTE (OR = 17.4; p = 0.01) controlling for age, LOS, and ambulatory disability. Conclusion: NMOSD may be a risk factor for VTE. Larger prospective studies are required to confirm this risk and determine implications for prophylaxis.