scholarly journals Novel Heterozygous Variants in the HLA-DRB1 Gene in a Saudi Family with Early-Onset Familial Multiple Sclerosis: Therapeutic Failure and Success

2021 ◽  
Author(s):  
Hussein Algahtani ◽  
Bader Shirah ◽  
Randa Khafaji ◽  
Sarah Algahtani
Keyword(s):  
Multiple Sclerosis ◽  
Large Scale ◽  
Family Work ◽  
Drb1 Gene ◽  
Disease Modifying Therapy ◽  
Novel Variants ◽  
Saudi Family ◽  
The Central Nervous System ◽  
Chance Occurrence ◽  
Work Up

Abstract Multiple sclerosis (MS) is a chronic neurodegenerative disease that affects the central nervous system. Familial MS is arbitrarily defined as a type of MS that runs in families with one or more first- to third-degree relatives in addition to the index case affected by MS. The aim of this article is to report a unique case of familial MS from Saudi Arabia with two novel variants in the HLA-DRB1 gene that may contribute to the pathogenesis. We observed an unfavorable response to interferon therapy and successful treatment using fingolimod therapy. This observation needs further study, including whether this lack of response is really specific to interferon treatment or possibly a chance occurrence. This family work-up illustrates the importance of genetic testing in identifying variants associated with familial MS, especially if more than two members of the same family are affected. Although this genetic tool is used mainly for research purposes, it had clinical implications for our patient, including the appropriate selection of disease-modifying therapy and prognostic counseling. Further large-scale studies are needed to expand the genetic spectrum of familial MS with clinical and pharmacologic correlation.

scholarly journals The Interaction between Viral and Environmental Risk Factors in the Pathogenesis of Multiple Sclerosis

2019 ◽  
Vol 20 (2) ◽  
pp. 303 ◽  
Author(s):  
Rachael Tarlinton ◽  
Timur Khaibullin ◽  
Evgenii Granatov ◽  
Ekaterina Martynova ◽  
Albert Rizvanov ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Large Scale ◽  
Motor Impairment ◽  
Endogenous Retrovirus ◽  
Barr Virus ◽  
Scale Population ◽  
Epidemiological Risk ◽  
The Central Nervous System ◽  
Epstein Barr

Multiple sclerosis (MS) is a chronic debilitating inflammatory disease of unknown ethology targeting the central nervous system (CNS). MS has a polysymptomatic onset and is usually first diagnosed between the ages of 20–40 years. The pathology of the disease is characterized by immune mediated demyelination in the CNS. Although there is no clinical finding unique to MS, characteristic symptoms include sensory symptoms visual and motor impairment. No definitive trigger for the development of MS has been identified but large-scale population studies have described several epidemiological risk factors for the disease. This list is a confusing one including latitude, vitamin D (vitD) levels, genetics, infection with Epstein Barr Virus (EBV) and endogenous retrovirus (ERV) reactivation. This review will look at the evidence for each of these and the potential links between these disparate risk factors and the known molecular disease pathogenesis to describe potential hypotheses for the triggering of MS pathology.

A case of immune-mediated encephalitis related to daclizumab therapy

2018 ◽  
Vol 25 (5) ◽  
pp. 750-753 ◽  
Author(s):  
Michael Devlin ◽  
Andrew Swayne ◽  
Martin Newman ◽  
Cullen O’Gorman ◽  
Helen Brown ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Reactions ◽  
Brain Biopsy ◽  
Disease Modifying Therapy ◽  
Immune Mediated ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Disease Modifying ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Csf Examination

This report will detail a case of immune-mediated encephalitis in the context of daclizumab therapy. Daclizumab is a humanised monoclonal antibody which, prior to its recent worldwide withdrawal due to safety concerns, was utilised as a disease-modifying therapy in relapsing-remitting multiple sclerosis. The withdrawal of this therapy was prompted by concerns over 12 cases of serious immune-mediated adverse reactions in the central nervous system. We report an additional case, including clinical data and results of neuroimaging, cerebrospinal fluid (CSF) examination and brain biopsy.

scholarly journals Disease Modifying Therapy in Multiple Sclerosis

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
U. E. Williams ◽  
S. K. Oparah ◽  
E. E. Philip-Ephraim
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Axonal Degeneration ◽  
Genetic Factors ◽  
Permanent Disability ◽  
Disease Modifying Drugs ◽  
Disease Modifying Therapy ◽  
Neuroprotective Therapy ◽  
The Central Nervous System ◽  
Disease Modifying

Multiple sclerosis is an autoimmune disease of the central nervous system characterized by inflammatory demyelination and axonal degeneration. It is the commonest cause of permanent disability in young adults. Environmental and genetic factors have been suggested in its etiology. Currently available disease modifying drugs are only effective in controlling inflammation but not prevention of neurodegeneration or accumulation of disability. Search for an effective neuroprotective therapy is at the forefront of multiple sclerosis research.

scholarly journals Case Report: Persisting Lymphopenia During Neuropsychiatric Tumefactive Multiple Sclerosis Rebound Upon Fingolimod Withdrawal

2021 ◽  
Vol 12 ◽  
Author(s):  
Valeria Koska ◽  
Moritz Förster ◽  
Katja Brouzou ◽  
Ercan Arat ◽  
Philipp Albrecht ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Opportunistic Infections ◽  
Neuropsychiatric Symptoms ◽  
Severe Disease ◽  
Mass Effect ◽  
Disease Modifying Therapy ◽  
Perifocal Edema ◽  
Demyelinating Lesions ◽  
The Central Nervous System ◽  
Relapsing Remitting Multiple Sclerosis

Fingolimod (FTY) is a disease modifying therapy for relapsing remitting multiple sclerosis (RRMS) which can lead to severe lymphopenia requiring therapy discontinuation in order to avoid adverse events. However, this can result in severe disease reactivation occasionally presenting with tumefactive demyelinating lesions (TDLs). TDLs, which are thought to originate from a massive re-entry of activated lymphocytes into the central nervous system, are larger than 2 cm in diameter and may feature mass effect, perifocal edema, and gadolinium enhancement. In these cases, it can be challenging to exclude important differential diagnoses for TDLs such as progressive multifocal leukoencephalopathy (PML) or other opportunistic infections. Here, we present the case of a 26-year-old female patient who suffered a massive rebound with TDLs following FTY discontinuation with primarily neuropsychiatric symptoms despite persisting lymphopenia. Two cycles of seven plasmaphereses each were necessary to achieve remission and ocrelizumab was used for long-term stabilization.

A Case of Intractable Vomiting

2018 ◽  
pp. 157-162
Author(s):  
Aaron E. Miller ◽  
Tracy M. DeAngelis ◽  
Michelle Fabian ◽  
Ilana Katz Sand
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Area Postrema ◽  
Inflammatory Disorder ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Clinical Imaging ◽  
Prompt Treatment ◽  
Disease Modifying Therapy ◽  
The Central Nervous System ◽  
Disease Modifying

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disorder affecting the central nervous system, with clinical, imaging, and laboratory characteristics that are distinct from multiple sclerosis. It presents most commonly with optic neuritis, myelitis, or an area postrema syndrome consisting of intractable nausea, vomiting, or hiccups. Most patients are positive for serum antibodies to aquaporin 4. Prompt treatment with corticosteroids and/or plasma exchange is critical for recovery, as is the initiation of disease-modifying therapy with an immunomodulatory agent to prevent future attacks. First-line disease-modifying therapies for NMOSD include rituximab, mycophenolate mofetil, and azathioprine. Several additional agents are used less commonly, and others are currently in clinical trials.

scholarly journals Antidepressant Drug Treatment in Association with Multiple Sclerosis Disease-Modifying Therapy

2016 ◽  
Vol 18 (6) ◽  
pp. 305-310 ◽  
Author(s):  
Matthew M. Mirsky ◽  
Ruth Ann Marrie ◽  
Alexander Rae-Grant
Keyword(s):  
Multiple Sclerosis ◽  
Drug Use ◽  
Performance Management ◽  
Large Scale ◽  
Antidepressant Drug ◽  
Dimethyl Fumarate ◽  
Disease Modifying Therapy ◽  
Multiple Sclerosis Disease ◽  
Disease Modifying ◽  
The Relationship

Background: The Explorys Enterprise Performance Management (EPM) database contains de-identified clinical data for 50 million patients. Multiple sclerosis (MS) disease-modifying therapies (DMTs), specifically interferon beta (IFNβ) treatments, may potentiate depression. Conflicting data have emerged, and a large-scale claims-based study by Patten et al. did not support such an association. This study compares the results of Patten et al. with those using the EPM database. Methods: “Power searches” were built to test the relationship between antidepressant drug use and DMT in the MS population. Searches were built to produce a cohort of individuals diagnosed as having MS in the past 3 years taking a specific DMT who were then given any antidepressant drug. The antidepressant drug therapy prevalence was tested in the MS population on the following DMTs: IFNβ-1a, IFNβ-1b, combined IFNβ, glatiramer acetate, natalizumab, fingolimod, and dimethyl fumarate. Results: In patients with MS, the rate of antidepressant drug use in those receiving DMTs was 40.60% to 44.57%. The rate of antidepressant drug use for combined IFNβ DMTs was 41.61% (males: 31.25%–39.62%; females: 43.10%–47.33%). Antidepressant drug use peaked in the group aged 45 to 54 years for five of six DMTs. Conclusions: We found no association between IFNβ treatment and antidepressant drug use in the MS population compared with other DMTs. The EPM database has been validated against the Patten et al. data for future use in the MS population.

scholarly journals Clinical Immunological Correlations in Patients with Multiple Sclerosis Treated with Natalizumab

2020 ◽  
Vol 10 (11) ◽  
pp. 802
Author(s):  
Smaranda Maier ◽  
Mihaela Simu ◽  
Adina Hutanu ◽  
Laura Barcutean ◽  
Septimiu Voidazan ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Inflammatory Cytokines ◽  
Biological Effects ◽  
Serum Levels ◽  
Clinical Activity ◽  
Disability Score ◽  
Necrosis Factor Alpha ◽  
Disease Modifying Therapy ◽  
The Central Nervous System ◽  
Anti Inflammatory

Natalizumab (NAT) was the first disease modifying therapy used for the treatment of relapsing-remitting multiple sclerosis (MS) that was designed with a specific mechanism of action that targets an important step of the MS immunopathology, directly blocking the T lymphocyte intrusion in the central nervous system. Initially, it was considered that NAT carried no biological effects on the peripheral immune response. The purpose of our study was to assess the effects of NAT on the peripheral pro and anti-inflammatory cytokines and to reveal possible correlations between them and the clinical activity of the disease. We noticed a significant decrease in interleukin (IL)-17, tumor necrosis factor-alpha (TNF-α) and IL-31 serum levels in treated patients. The lack of relapses during the study was associated with low baseline IL-17 level. The patients that had an increase in the disability score during the study had significantly lower IL-17 and higher IL-1β baseline levels. IL-17 can be used as a biomarker for disease activity but also for progression assessment in NAT treated patients. NAT has a far more complex mechanism compared to what was initially believed, besides modulating lymphocyte trafficking through the blood–brain barrier, it also changes the peripheral levels of pro and anti-inflammatory cytokines in MS patients.

scholarly journals Altered cortical phase- and amplitude-coupling in Multiple Sclerosis

2021 ◽  
Author(s):  
Marcus Siems ◽  
Johannes Tünnerhoff ◽  
Ulf Ziemann ◽  
Markus Siegel
Keyword(s):  
Multiple Sclerosis ◽  
Large Scale ◽  
Demyelinating Disease ◽  
Disease Stage ◽  
Functional Changes ◽  
Non Invasive ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

AbstractMultiple Sclerosis is a demyelinating disease of the central nervous system that can result in cognitive decline and physical disability. However, related functional changes in large-scale brain interactions remain poorly understood and corresponding non-invasive biomarkers are sparse. Here, we measured magnetoencephalography in 17 relapsing-remitting Multiple Sclerosis patients at an early disease stage (median EDSS = 1.5, range 0 to 3.5) and 17 healthy controls to investigate brain-wide phase- and amplitude-coupling of frequency specific neuronal activity. We developed a new analysis approach that combines dimensionality reduction, bootstrap aggregating and multivariate classification to identify changes of brain-wide coupling in Multiple Sclerosis. We identified systematic and non-redundant changes of both phase- and amplitude-coupling. Changes included both, increased and decreased neuronal coupling in wide-spread, bilateral neuronal networks across a broad range of frequencies. These changes allowed to successfully classify patients and controls with an accuracy of 84%. Furthermore, classification confidence predicted behavioral scores of disease severity. Our results unravel systematic changes of large-scale neuronal coupling in Multiple Sclerosis and suggest non-invasive electrophysiological coupling measures as powerful biomarkers of Multiple Sclerosis.

Cold-induced reactivity in multiple sclerosis patients

2017 ◽  
pp. 56-62 ◽  
Author(s):  
Л.И. Герасимова-Мейгал ◽  
И.М. Сиренев
Keyword(s):  
Multiple Sclerosis ◽  
Cold Test ◽  
Typical Feature ◽  
Humid Climate ◽  
Ssr Analysis ◽  
Epidemiological Surveys ◽  
The Central Nervous System ◽  
The Individual ◽  
Hands And Feet ◽  
Multiple Sclerosis Patients

Цель исследования - изучение особенностей восприимчивости пациентов с рассеянным склерозом (РС) к холодовому воздействию с помощью функциональных тестов, характеризующих функцию терморегуляции. Как известно, РС - хроническое прогрессирующее аутоиммунное заболевание центральной нервной системы мультифакториальной природы, более часто встречающееся в регионах с холодным и влажным климатом. Нарушения терморегуляции вследствие автономной дисфункции являются характерным признаком РС, вместе с тем участию холодового фактора в развитии заболевания не придается существенного значения. Методика. Обследовано 32 пациента (17 мужчин и 15 женщин, средний возраст 29,6 ± 4,2 года) с установленным диагнозом: РС ремиттирующе-рецидивирующая форма течения (средняя продолжительность заболевания - 4,2 ± 2,7 года) и 18 практически здоровых лиц группы сравнения. Восприятие холода оценивали с помощью визуально-аналоговой шкалы. Продолжительность холод-индуцированной вазоконстрикции после локального холодового теста изучали по данным инфракрасной термометрии. Вегетативную регуляцию вазомоторных реакций оценивали по результатам анализа вызванных кожных вегетативных потенциалов (ВКВП). Результаты. На основе анализа самооценки восприятия холода у пациентов с РС показана низкая переносимость холодового фактора. При проведении локального холодового теста отмечено замедление восстановления температуры кожи кисти, что характерно для усиления холод-индуцированной вазоконстрикции. В группе пациентов с РС выявлено снижение параметров ВКВП ладоней и стоп, свидетельствующее о дефиците нейрогенного контроля терморегуляционных сосудистых реакций. Заключение. У пациентов с РС выявлены нарушения механизмов терморегуляции при действии холода, что обусловливает высокую индивидуальную восприимчивость к холоду у данной категории лиц. Сопоставление результатов анализа механизмов индивидуальной холод-индуцированной реактивности у пациентов с РС с данными эпидемиологических исследований приводит к заключению о потенциальном модулирующем влиянии холодового фактора на течение РС. The purpose of the present study was focused on the evaluation of the sensitivity to cold in multiple sclerosis (MS) patients by means of functional thermoregulatory based tests. MS is known to be a chronic autoimmune progressive disease of the central nervous system of multifactor origin that is very common in regions with cold and humid climate. Disorder of thermoregulation caused by autonomic dysfunction is a typical feature of MS, however the role of the cold in the disease development is still underestimated. Methods. Thirty two MS patients (17 males, 15 females, mean age 29,6 ± 4,2 years) with the remittent form of the disease (mean disease duration 4,2 ± 2,7 years) and 18 age-matched healthy controls volunteered to participate in this study. Susceptibility to cold was analyzed with the use of visual-analogous scale. The duration of cold-induced vasoconstriction after local cold test was estimated using by infrared thermometry. Autonomic regulation of vasomotor reactions was investigated with the help of the skin sympathetic response (SSR) analysis. Results. The analysis of self-reported perception of the cold in MS patients showed their low tolerance to cold. Slow recovery of the skin temperature of the hand in the local cold test observed in MS patients was considered as the aggravated cold-induced vasoconstriction. The decreased SSR in the hands and feet in MS patients was found that indicates the deficit of the neurogenic control of thermoregulatory vasomotor reactions. Conclusion. The results obtained demonstrate the impairment of thermoregulation under cold in MS patients that leads to higher individual susceptibility to cold of this group. Comparing of the data found in this study on the mechanisms of the individual cold-induced reactivity in MS patients with epidemiological surveys enable to conclude that cold environment has potential modulating effect of on the course of MS.

Sign in / Sign up

Export Citation Format

Share Document