An Overview of Multiple Sclerosis: Medical, Psychosocial, and Vocational Aspects of a Chronic and Unpredictable Neurological Disorder

ERIC Educational Resources Information Center

Rumrill, Phillip D., Jr.; Roessler, Richard T.

2015-01-01

This article presents an overview of multiple sclerosis (MS), one of the most common neurological disorders in the western hemisphere. Medical and psychosocial aspects of the disease such as causes and risk factors, diagnosis, incidence and prevalence, symptoms, courses, and treatment are described. Existing research regarding the employment…

Epstein Barr Virus and Blood Brain Barrier in Multiple Sclerosis

DTIC Science & Technology

2014-01-01

ABSTRACT Multiple sclerosis (MS) is a chronic, autoimmune neurodegenerative disease . Epstein - Barr virus (EBV) infection is associated with MS...factors such as Epstein - Barr virus (EBV) infections. EBV is a herpesvirus that infects many cell types and associated with other autoimmune diseases . The...AD_________________ Award Number: W81XWH-12-1-0225 TITLE: Epstein Barr virus and

The Swedish version of the Acceptance of Chronic Health Conditions Scale for people with multiple sclerosis: Translation, cultural adaptation and psychometric properties.

PubMed

Forslin, Mia; Kottorp, Anders; Kierkegaard, Marie; Johansson, Sverker

2016-11-11

To translate and culturally adapt the Acceptance of Chronic Health Conditions (ACHC) Scale for people with multiple sclerosis into Swedish, and to analyse the psychometric properties of the Swedish version. Ten people with multiple sclerosis participated in translation and cultural adaptation of the ACHC Scale; 148 people with multiple sclerosis were included in evaluation of the psychometric properties of the scale. Translation and cultural adaptation were carried out through translation and back-translation, by expert committee evaluation and pre-test with cognitive interviews in people with multiple sclerosis. The psychometric properties of the Swedish version were evaluated using Rasch analysis. The Swedish version of the ACHC Scale was an acceptable equivalent to the original version. Seven of the original 10 items fitted the Rasch model and demonstrated ability to separate between groups. A 5-item version, including 2 items and 3 super-items, demonstrated better psychometric properties, but lower ability to separate between groups. The Swedish version of the ACHC Scale with the original 10 items did not fit the Rasch model. Two solutions, either with 7 items (ACHC-7) or with 2 items and 3 super-items (ACHC-5), demonstrated acceptable psychometric properties. Use of the ACHC-5 Scale with super-items is recommended, since this solution adjusts for local dependency among items.

FGF-2 and Anosmin-1 are selectively expressed in different types of multiple sclerosis lesions.

PubMed

Clemente, Diego; Ortega, María Cristina; Arenzana, Francisco Javier; de Castro, Fernando

2011-10-19

Multiple sclerosis is a demyelinating disease that affects ≈ 2,000,000 people worldwide. In the advanced stages of the disease, endogenous oligodendrocyte precursors cannot colonize the lesions or differentiate into myelinating oligodendrocytes. During development, both FGF-2 and Anosmin-1 participate in oligodendrocyte precursor cell migration, acting via the FGF receptor 1 (FGFR1). Hence, we performed a histopathological and molecular analysis of these developmental modulators in postmortem tissue blocks from multiple sclerosis patients. Accordingly, we demonstrate that the distribution of FGF-2 and Anosmin-1 varies between the different types of multiple sclerosis lesions: FGF-2 is expressed only within active lesions and in the periplaque of chronic lesions, whereas Anosmin-1 is upregulated within chronic lesions and is totally absent in active lesions. We show that the endogenous oligodendrocyte precursor cells recruited toward chronic-active lesions express FGFR1, possibly in response to the FGF-2 produced by microglial cells in the periplaque. Also in human tissue, FGF-2 is upregulated in perivascular astrocytes in regions of the normal-appearing gray matter, where the integrity of the blood-brain barrier is compromised. In culture, FGF-2 and Anosmin-1 influence adult mouse oligodendrocyte precursor cell migration in the same manner as at embryonic stages, providing an explanation for the histopathological observations: FGF-2 attracts/enhances its migration, which is hindered by Anosmin-1. We propose that FGF-2 and Anosmin-1 are markers for the histopathological type and the level of inflammation of multiple sclerosis lesions, and that they may serve as novel pharmacogenetic targets to design future therapies that favor effective remyelination and protect the blood-brain barrier.

Venous compression syndrome of internal jugular veins prevalence in patients with multiple sclerosis and chronic cerebro-spinal venous insufficiency.

PubMed

Mandolesi, Sandro; Niglio, Tarcisio; Orsini, Augusto; De Sio, Simone; d'Alessandro, Alessandro; Mandolesi, Dimitri; Fedele, Francesco; d'Alessandro, Aldo

2016-01-01

Analysis of the incidence of Venous Compression Syndrome (VCS) with full block of the flow of the internal jugular veins (IJVs) in patients with Multiple Sclerosis and Chronic cerebro-spinal venous insufficiency. We included 769 patients with MS and CCSVI (299 males, 470 females) and 210 controls without ms and ccsvi (92 males, 118 females). each subject was investigated by echo-color-doppler (ecd). morphological and hemodynamic ecd data were recorded by a computerized mem-net maps of epidemiological national observatory on ccsvi and they were analyzed by mem-net clinical analysis programs. VCS of IJVs occurs in 240 subjects affected by CCSVI and MS (31% of total) and in 12 controls (6% of total). The differences between the two groups are statistical significant (X² = 36.64, p<0.0001). Up to day there are no longitudinal studies that allow us to identify the WC of jugular and/or vertebral veins as etiology of a chronic neurodegenerative disease, but we note that Venous Compression Syndrome of IJVs is strongly associated with MS and CCSVI. Chronic Cerebro-Spinal Venous Insufficiency, Multiple Sclerosis, Venous Compression Syndrome.

[Physical rehabilitation in multiple sclerosis: general principles and high-tech approaches].

PubMed

Peresedova, A V; Chernikova, L A; Zavalishin, I A

2013-01-01

In a chronic and disabling disease like multiple sclerosis, rehabilitation programs are of major importance for the preservation of physical, physiological, social and professional functioning and improvement of quality of life. Currently, it is generally assumed that physical activity is an important component of non-pharmacological rehabilitation in multiple sclerosis. Properly organized exercise is a safe and efficient way to induce improvements in a number of physiological functions. A multidisciplinary rehabilitative approach should be recommended. The main recommendations for the use of exercise for patients with multiple sclerosis have been listed. An important aspect of the modern physical rehabilitation in multiple sclerosis is the usage of high-tech methods. The published results of robot-assisted training to improve the hand function and walking impairment have been represented. An important trend in the rehabilitation of patients with multiple sclerosis is the reduction of postural disorders through training balance coordination. The role of transcranial magnetic stimulation in spasticity reducing is being investigated. The use of telemedicine capabilities is quite promising. Due to the fact that the decline in physical activity can lead to the deterioration of many aspects of physiological functions and, ultimately, to mobility decrease, further research of the role of physical rehabilitation as an important therapeutic approach in preventing the progression of disability in multiple sclerosis is required.

Determining the IgM and IgG antibody titer against CMV and helicobacter pylori in the serum of multiple sclerosis patients comparing to the control group in Hamadan.

PubMed

Salim, Masome Afiati; Eftekharian, Mohammad Mahdi; Taheri, Mohammad; Yousef Alikhani, Mohammad

2017-07-19

Multiple sclerosis (MS) is a chronic autoimmune disease that disables central nervous system (CNS) system. Cytomegalovirus (CMV) probably has an important role in the MS pathology. The infection with helicobacter pylori also is recognized as a protective agent against MS in female. Serum samples were isolated and frozen at -70∘C. The earlier mentioned anti-virus antibodies and antibacterial antibodies were quantified by Elisa kit. The results showed that IgG antibody average value against cytomegalovirus in the blood of multiple sclerosis patients not only decreased but also was significant statistically (p< 0.05). IgM and IgG antibodies average value in the blood of multiple sclerosis patients against helicobacter pylori shown a statistically significant decrease (p< 0.05). Therefore it may be considered that probably helicobacter pylori presence in the individuals especially in female can alleviate MS signs. CMV infection can intensify the symptoms in multiple sclerosis patients.

Interleukin 35 and Hepatocyte Growth Factor; as a novel combined immune gene therapy for Multiple Sclerosis disease.

PubMed

Moghadam, Samira; Erfanmanesh, Maryam; Esmaeilzadeh, Abdolreza

2017-11-01

An autoimmune demyelination disease of the Central Nervous System, Multiple Sclerosis, is a chronic inflammation which mostly involves young adults. Suffering people face functional loss with a severe pain. Most current MS treatments are focused on the immune response suppression. Approved drugs suppress the inflammatory process, but factually, there is no definite cure for Multiple Sclerosis. Recently developed knowledge has demonstrated that gene and cell therapy as a hopeful approach in tissue regeneration. The authors propose a novel combined immune gene therapy for Multiple Sclerosis treatment using anti-inflammatory and remyelination of Interleukine-35 and Hepatocyte Growth Factor properties, respectively. In this hypothesis Interleukine-35 and Hepatocyte Growth Factor introduce to Mesenchymal Stem Cells of EAE mouse model via an adenovirus based vector. It is expected that Interleukine-35 and Hepatocyte Growth Factor genes expressed from MSCs could effectively perform in immunotherapy of Multiple Sclerosis. Copyright © 2017. Published by Elsevier Ltd.

Axonal loss in the multiple sclerosis spinal cord revisited.

PubMed

Petrova, Natalia; Carassiti, Daniele; Altmann, Daniel R; Baker, David; Schmierer, Klaus

2018-05-01

Preventing chronic disease deterioration is an unmet need in people with multiple sclerosis, where axonal loss is considered a key substrate of disability. Clinically, chronic multiple sclerosis often presents as progressive myelopathy. Spinal cord cross-sectional area (CSA) assessed using MRI predicts increasing disability and has, by inference, been proposed as an indirect index of axonal degeneration. However, the association between CSA and axonal loss, and their correlation with demyelination, have never been systematically investigated using human post mortem tissue. We extensively sampled spinal cords of seven women and six men with multiple sclerosis (mean disease duration= 29 years) and five healthy controls to quantify axonal density and its association with demyelination and CSA. 396 tissue blocks were embedded in paraffin and immuno-stained for myelin basic protein and phosphorylated neurofilaments. Measurements included total CSA, areas of (i) lateral cortico-spinal tracts, (ii) gray matter, (iii) white matter, (iv) demyelination, and the number of axons within the lateral cortico-spinal tracts. Linear mixed models were used to analyze relationships. In multiple sclerosis CSA reduction at cervical, thoracic and lumbar levels ranged between 19 and 24% with white (19-24%) and gray (17-21%) matter atrophy contributing equally across levels. Axonal density in multiple sclerosis was lower by 57-62% across all levels and affected all fibers regardless of diameter. Demyelination affected 24-48% of the gray matter, most extensively at the thoracic level, and 11-13% of the white matter, with no significant differences across levels. Disease duration was associated with reduced axonal density, however not with any area index. Significant association was detected between focal demyelination and decreased axonal density. In conclusion, over nearly 30 years multiple sclerosis reduces axonal density by 60% throughout the spinal cord. Spinal cord cross sectional area, reduced by about 20%, appears to be a poor predictor of axonal density. © 2017 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

[Axonopathy in the pathogenesis of multiple sclerosis, peripheral diffuse and local motor neuropathies and motor neuron disease].

PubMed

Merkulov, Iu A; Merkulova, D M; Iosifova, O A; Zavalishin, I A

2010-01-01

Two hundreds and seventy-six patients including 43 patients with multiple sclerosis, 24 - with acute inflammatory demyelinating polyneuropathy (AIDP), 144 - with chronic inflammatory demyelinating polyneuropathy (CIDP), 27 - with motor multifocal neuropathy (MMN), 38 - with lateral amyotrophic sclerosis (LAS) have been examined. Symptoms of axonal degeneration, manifested in denervation phenomena in both clinical and instrumental studies (electromyography, transcranial magnetic stimulation, MRT), were revealed in all groups of patients. The formation of excitation conduction blocks is an universal pathophysiological mechanism of the axonopathy development in AIDP, CIDP, MMN and LAS. Symptoms of axonopathy and peripheral demyelinization in patients with multiple sclerosis and LAS suggest the possibility of transformation of immunopathological process from the central nervous system to the peripheral one.

Multiple sclerosis - etiology and diagnostic potential.

PubMed

Kamińska, Joanna; Koper, Olga M; Piechal, Kinga; Kemona, Halina

2017-06-30

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS) damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPSM), primary progressive multiple sclerosis (PPMS), and progressive-relapsing multiple sclerosis (RPMS). Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald's diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of different diagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

Immunopharmacological role of the leukotriene receptor antagonists and inhibitors of leukotrienes generating enzymes in multiple sclerosis.

PubMed

Mirshafiey, Abbas; Jadidi-Niaragh, Farhad

2010-06-01

Multiple sclerosis (MS) is a chronic inflammatory disease that involves central nervous system, and is generally associated with demyelination and axonal lesion. The effective factors for initiation of the inflammatory responses have not been known precisely so far. Leukotrienes (LTs) are inflammatory mediators with increased levels in the cerebrospinal fluid of MS patients and in experimental models of multiple sclerosis. Inhibition of LT receptors with specific antagonists can decrease inflammatory responses. In this review article we try to clarify the role of LT receptor antagonists and also inhibitors of enzymes which are involved in LTs generating pathway for treating multiple sclerosis as new targets for MS therapy. Moreover, we suggest that blockage of LT receptors by potent specific antagonists and/or agonists can be as a novel useful method in treatment of MS.

Up-Regulation of Soluble Axl and Mer Receptor Tyrosine Kinases Negatively Correlates with Gas6 in Established Multiple Sclerosis Lesions

PubMed Central

Weinger, Jason G.; Omari, Kakuri M.; Marsden, Kurt; Raine, Cedric S.; Shafit-Zagardo, Bridget

2009-01-01

Multiple sclerosis is a disease that is characterized by inflammation, demyelination, and axonal damage; it ultimately forms gliotic scars and lesions that severely compromise the function of the central nervous system. Evidence has shown previously that altered growth factor receptor signaling contributes to lesion formation, impedes recovery, and plays a role in disease progression. Growth arrest-specific protein 6 (Gas6), the ligand for the TAM receptor tyrosine kinase family, consisting of Tyro3, Axl, and Mer, is important for cell growth, survival, and clearance of debris. In this study, we show that levels of membrane-bound Mer (205 kd), soluble Mer (∼150 kd), and soluble Axl (80 kd) were all significantly elevated in homogenates from established multiple sclerosis lesions comprised of both chronic active and chronic silent lesions. Whereas in normal tissue Gas6 positively correlated with soluble Axl and Mer, there was a negative correlation between Gas6 and soluble Axl and Mer in established multiple sclerosis lesions. In addition, increased levels of soluble Axl and Mer were associated with increased levels of mature ADAM17, mature ADAM10, and Furin, proteins that are associated with Axl and Mer solubilization. Soluble Axl and Mer are both known to act as decoy receptors and block Gas6 binding to membrane-bound receptors. These data suggest that in multiple sclerosis lesions, dysregulation of protective Gas6 receptor signaling may prolong lesion activity. PMID:19541935

"A Group of Me's": Adult Learning through Group Process: The Experiences of Participants in a Teleconference Delivered Multiple Sclerosis Fatigue Management Program

ERIC Educational Resources Information Center

Preissner, Katharine L.

2013-01-01

Multiple sclerosis (MS) is a chronic, progressive neurological disorder that affects approximately 2.1 million people worldwide. Fatigue is one of the most common and most disabling symptoms of MS. One well-established approach to address fatigue is fatigue management education provided by an occupational therapist. Fatigue management education is…

Relationship of acute axonal damage, Wallerian degeneration, and clinical disability in multiple sclerosis.

PubMed

Singh, Shailender; Dallenga, Tobias; Winkler, Anne; Roemer, Shanu; Maruschak, Brigitte; Siebert, Heike; Brück, Wolfgang; Stadelmann, Christine

2017-03-17

Axonal damage and loss substantially contribute to the incremental accumulation of clinical disability in progressive multiple sclerosis. Here, we assessed the amount of Wallerian degeneration in brain tissue of multiple sclerosis patients in relation to demyelinating lesion activity and asked whether a transient blockade of Wallerian degeneration decreases axonal loss and clinical disability in a mouse model of inflammatory demyelination. Wallerian degeneration and acute axonal damage were determined immunohistochemically in the periplaque white matter of multiple sclerosis patients with early actively demyelinating lesions, chronic active lesions, and inactive lesions. Furthermore, we studied the effects of Wallerian degeneration blockage on clinical severity, inflammatory pathology, acute axonal damage, and long-term axonal loss in experimental autoimmune encephalomyelitis using Wallerian degeneration slow (Wld S ) mutant mice. The highest numbers of axons undergoing Wallerian degeneration were found in the perilesional white matter of multiple sclerosis patients early in the disease course and with actively demyelinating lesions. Furthermore, Wallerian degeneration was more abundant in patients harboring chronic active as compared to chronic inactive lesions. No co-localization of neuropeptide Y-Y1 receptor, a bona fide immunohistochemical marker of Wallerian degeneration, with amyloid precursor protein, frequently used as an indicator of acute axonal transport disturbance, was observed in human and mouse tissue, indicating distinct axon-degenerative processes. Experimentally, a delay of Wallerian degeneration, as observed in Wld S mice, did not result in a reduction of clinical disability or acute axonal damage in experimental autoimmune encephalomyelitis, further supporting that acute axonal damage as reflected by axonal transport disturbances does not share common molecular mechanisms with Wallerian degeneration. Furthermore, delaying Wallerian degeneration did not result in a net rescue of axons in late lesion stages of experimental autoimmune encephalomyelitis. Our data indicate that in multiple sclerosis, ongoing demyelination in focal lesions is associated with axonal degeneration in the perilesional white matter, supporting a role for focal pathology in diffuse white matter damage. Also, our results suggest that interfering with Wallerian degeneration in inflammatory demyelination does not suffice to prevent acute axonal damage and finally axonal loss.

Controlled randomised crossover trial of the effects of physiotherapy on mobility in chronic multiple sclerosis

PubMed Central

Wiles, C; Newcombe, R; Fuller, K; Shaw, S; Furnival-Doran, J; Pickersgill, T; Morgan, A

2001-01-01

OBJECTIVES—To determine whether physiotherapy can improve mobility in chronic multiple sclerosis and whether there is a difference between treatment at home and as a hospital outpatient?
METHODS—A randomised controlled crossover trial was undertaken in patients with chronic multiple sclerosis who had difficulty walking and were referred from neurology clinics: allocation was to one of six permutations of three 8 week treatment periods separated by 8 week intervals: treatments consisted of physiotherapy at home, as an outpatient, or "no therapy". The main outcome measures were based on independent assessments at home and included mobility related disability (primary outcome: the Rivermead mobility index), gait impairments, arm function, mood, and subjective patient and carer ratings. Therapy was assessed by recording delivery, achievement of set targets, patient and carer preference, and cost.
RESULTS—On the Rivermead mobility index (scale 0-15) (primary outcome) there was a highly significant (p<0.001) treatment effect of 1.4-1.5 units favouring hospital or home based therapy over no therapy: this was supported by other measures of mobility, gait, balance, and the assessor's global "mobility change" score: there was no major difference between home and hospital. Carers preferred home treatment but neither they nor patients discerned greater benefit there. Estimated costs of home physiotherapy were £25/session and those at hospital were £18 (including £7 patient travel costs).
CONCLUSION—A course of physiotherapy is associated with improved mobility, subjective wellbeing, and improved mood in chronic multiple sclerosis compared with no treatment but benefit may only last a few weeks: there is little to choose between home and hospital based therapy but the first is more costly, mainly due to skilled staff travelling time.

 PMID:11160464

Heart rate variability is differentially altered in multiple sclerosis: implications for acute, worsening and progressive disability.

PubMed

Studer, Valeria; Rocchi, Camilla; Motta, Caterina; Lauretti, Benedetta; Perugini, Jacopo; Brambilla, Laura; Pareja-Gutierrez, Lorena; Camera, Giorgia; Barbieri, Francesca Romana; Marfia, Girolama A; Centonze, Diego; Rossi, Silvia

2017-01-01

Sympathovagal imbalance has been associated with poor prognosis in chronic diseases, but there is conflicting evidence in multiple sclerosis. The objective of this study was to investigate the autonomic nervous system dysfunction correlation with inflammation and progression in multiple sclerosis. Heart rate variability was analysed in 120 multiple sclerosis patients and 60 healthy controls during supine rest and head-up tilt test; the normalised units of low frequency and high frequency power were considered to assess sympathetic and vagal components, respectively. Correlation analyses with clinical and radiological markers of disease activity and progression were performed. Sympathetic dysfunction was closely related to the progression of disability in multiple sclerosis: progressive patients showed altered heart rate variability with respect to healthy controls and relapsing-remitting patients, with higher rest low frequency power and lacking the expected low frequency power increase during the head-up tilt test. In relapsing-remitting patients, disease activity, even subclinical, was associated with lower rest low frequency power, whereas stable relapsing-remitting patients did not differ from healthy controls. Less sympathetic reactivity and higher low frequency power at rest were associated with incomplete recovery from relapse. Autonomic balance appears to be intimately linked with both the inflammatory activity of multiple sclerosis, which is featured by an overall hypoactivity of the sympathetic nervous system, and its compensatory plastic processes, which appear inefficient in case of worsening and progressive multiple sclerosis.

Parental Involvement of Mothers with Chronic Illness and Children's Academic Achievement

ERIC Educational Resources Information Center

Chen, Yung-Chi; Fish, Marian C.

2013-01-01

This study examined how maternal chronic illnesses may affect children's academic achievement through parental involvement. A total of 189 mothers diagnosed with chronic illnesses, such as multiple sclerosis, diabetes, cancer, HIV/AIDS, chronic pain, asthma, myelodysplasic syndrome, and fibromyalgia, and with a child in middle school or high…

A rare condition of anorectal dysfunction in a patient with multiple sclerosis: Coexistence of faecal incontinence and mechanical constipation: Report of case

PubMed Central

Dandin, Özgür; Akpak, Yaşam Kemal; Karakaş, Dursun Özgür; Hazer, Batuhan; Ergin, Tuncer; Dandinoğlu, Taner; Teomete, Uygar

2014-01-01

INTRODUCTION Multiple sclerosis is a chronic demyelinating neurological disease and causing a variety of neurological symptoms, including discomfort of anorectal function. Constipation and faecal incontinence present as anorectal dysfunction in MS and anal manometry, colonic transit time, electromyography, and defecography can be used for assessment. PRESENTATION OF CASE We presented a thirty-three years old woman with rare condition of anorectal dysfunction in multiple sclerosis. Anal manometry, defecography were done, and synchronously anal incontinence and mechanical constipation due to rectocele and anismus were detected in this patient. DISCUSSION Although anal incontinence and constipation are seen often in patients with multiple sclerosis, in the literature, coexistence of animus, rectocele and anal incontinence are quite rare. CONCLUSION Defecography and anal manometry are useful diagnostic methods for demonstration of anorectal dysfuntions in patients with MS. PMID:25460483

A rare condition of anorectal dysfunction in a patient with multiple sclerosis: Coexistence of faecal incontinence and mechanical constipation: Report of case.

PubMed

Dandin, Özgür; Akpak, Yaşam Kemal; Karakaş, Dursun Özgür; Hazer, Batuhan; Ergin, Tuncer; Dandinoğlu, Taner; Teomete, Uygar

2014-01-01

Multiple sclerosis is a chronic demyelinating neurological disease and causing a variety of neurological symptoms, including discomfort of anorectal function. Constipation and faecal incontinence present as anorectal dysfunction in MS and anal manometry, colonic transit time, electromyography, and defecography can be used for assessment. We presented a thirty-three years old woman with rare condition of anorectal dysfunction in multiple sclerosis. Anal manometry, defecography were done, and synchronously anal incontinence and mechanical constipation due to rectocele and anismus were detected in this patient. Although anal incontinence and constipation are seen often in patients with multiple sclerosis, in the literature, coexistence of animus, rectocele and anal incontinence are quite rare. Defecography and anal manometry are useful diagnostic methods for demonstration of anorectal dysfuntions in patients with MS. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Inflammation, Iron, Energy Failure, and Oxidative Stress in the Pathogenesis of Multiple Sclerosis

PubMed Central

Haider, Lukas

2015-01-01

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Different trigger pathologies have been suggested by the primary cytodegenerative “inside-out” and primary inflammation-driven “outside-in” hypotheses. Recent data indicate that mitochondrial injury and subsequent energy failure are key factors in the induction of demyelination and neurodegeneration. The brain weighs only a few percent of the body mass but accounts for approximately 20% of the total basal oxygen consumption of mitochondria. Oxidative stress induces mitochondrial injury in patients with multiple sclerosis and energy failure in the central nervous system of susceptible individuals. The interconnected mechanisms responsible for free radical production in patients with multiple sclerosis are as follows: (i) inflammation-induced production of free radicals by activated immune cells, (ii) liberation of iron from the myelin sheets during demyelination, and (iii) mitochondrial injury and thus energy failure-related free radical production. In the present review, the different sources of oxidative stress and their relationships to patients with multiple sclerosis considering tissue injury mechanisms and clinical aspects have been discussed. PMID:26106458

Striving for balance between caring and restraint: young adults' experiences with parental multiple sclerosis.

PubMed

Moberg, Julie Y; Larsen, Dorte; Brødsgaard, Anne

2017-05-01

To explore and describe how young adults between 18-25 years of age experienced growing up with a parent with multiple sclerosis and how these experiences continue to influence their daily lives. Chronic parental illness is occurring in about 10% of families worldwide, but little is known about how the children experience growing up with a parent with multiple sclerosis during their childhood and into young adulthood. We chose a qualitative design using a phenomenological approach based on Giorgi. Exploratory and open-ended interviews with 14 young adults were conducted. The essence of the phenomenon of having a parent with multiple sclerosis was synthesized into 'Striving for balance between caring and restraint' from two themes 'caring' and 'restraint' and eight subthemes. Participants' experiences of caring for parents with multiple sclerosis continued influencing their other close relationships, in which they tended to assume responsibility while concealing some of their feelings and desires. Most participants showed restraint among parents with and without multiple sclerosis, friends and partners. It seems that one of the greatest challenges of having a parent with multiple sclerosis is achieving a balance between caring for others and asserting one's own desires. Healthcare professionals can support the family by encouraging family members to participate in consultations and to assist the parents in providing information about multiple sclerosis and its symptoms to the children. Parents might need assistance in applying for help with domestic chores or referrals to support groups for their children or other family members. © 2016 John Wiley & Sons Ltd.

Effects of self-hypnosis training and cognitive restructuring on daily pain intensity and catastrophizing in individuals with multiple sclerosis and chronic pain.

PubMed

Jensen, Mark P; Ehde, Dawn M; Gertz, Kevin J; Stoelb, Brenda L; Dillworth, Tiara M; Hirsh, Adam T; Molton, Ivan R; Kraft, George H

2011-01-01

Fifteen adults with multiple sclerosis were given 16 sessions of treatment for chronic pain that included 4 sessions each of 4 different treatment modules: (a) an education control intervention; (b) self-hypnosis training (HYP); (c) cognitive restructuring (CR); and (d) a combined hypnosis-cognitive restructuring intervention (CR-HYP). The findings supported the greater beneficial effects of HYP, relative to CR, on average pain intensity. The CR-HYP treatment appeared to have beneficial effects greater than the effects of CR and HYP alone. Future research examining the efficacy of an intervention that combines CR and HYP is warranted.

[The possibility of using music therapy in neurology on the example of multiple sclerosis].

PubMed

Boiko, E A; Ivanchuk, E V; Gunchenko, M M; Batysheva, T T

2016-01-01

Currently music therapy plays an important role in the drug-free treatment and rehabilitation of children and adults with acute and chronic neurological and somatic diseases including demyelinating diseases. Existing studies show the effectiveness of music therapy in the improvement of social skills, cognitive function and sleep as well as in the reduction in the severity of depression, anxiety and pain in patients with multiple sclerosis.

[Magnetic Resonance Imaging Conversion Predictors of Clinically Isolated Syndrome to Multiple Sclerosis].

PubMed

Peixoto, Sara; Abreu, Pedro

2016-11-01

Clinically isolated syndrome may be the first manifestation of multiple sclerosis, a chronic demyelinating disease of the central nervous system, and it is defined by a single clinical episode suggestive of demyelination. However, patients with this syndrome, even with long term follow up, may not develop new symptoms or demyelinating lesions that fulfils multiple sclerosis diagnostic criteria. We reviewed, in clinically isolated syndrome, what are the best magnetic resonance imaging findings that may predict its conversion to multiple sclerosis. A search was made in the PubMed database for papers published between January 2010 and June 2015 using the following terms: 'clinically isolated syndrome', 'cis', 'multiple sclerosis', 'magnetic resonance imaging', 'magnetic resonance' and 'mri'. In this review, the following conventional magnetic resonance imaging abnormalities found in literature were included: lesion load, lesion location, Barkhof's criteria and brain atrophy related features. The non conventional magnetic resonance imaging techniques studied were double inversion recovery, magnetization transfer imaging, spectroscopy and diffusion tensor imaging. The number and location of demyelinating lesions have a clear role in predicting clinically isolated syndrome conversion to multiple sclerosis. On the other hand, more data are needed to confirm the ability to predict this disease development of non conventional techniques and remaining neuroimaging abnormalities. In forthcoming years, in addition to the established predictive value of the above mentioned neuroimaging abnormalities, different clinically isolated syndrome neuroradiological findings may be considered in multiple sclerosis diagnostic criteria and/or change its treatment recommendations.

Modeling month-season of birth as a risk factor in mouse models of chronic disease: from multiple sclerosis to autoimmune encephalomyelitis.

PubMed

Reynolds, Jacob D; Case, Laure K; Krementsov, Dimitry N; Raza, Abbas; Bartiss, Rose; Teuscher, Cory

2017-06-01

Month-season of birth (M-SOB) is a risk factor in multiple chronic diseases, including multiple sclerosis (MS), where the lowest and greatest risk of developing MS coincide with the lowest and highest birth rates, respectively. To determine whether M-SOB effects in such chronic diseases as MS can be experimentally modeled, we examined the effect of M-SOB on susceptibility of C57BL/6J mice to experimental autoimmune encephalomyelitis (EAE). As in MS, mice that were born during the M-SOB with the lowest birth rate were less susceptible to EAE than mice born during the M-SOB with the highest birth rate. We also show that the M-SOB effect on EAE susceptibility is associated with differential production of multiple cytokines/chemokines by neuroantigen-specific T cells that are known to play a role in EAE pathogenesis. Taken together, these results support the existence of an M-SOB effect that may reflect seasonally dependent developmental differences in adaptive immune responses to self-antigens independent of external stimuli, including exposure to sunlight and vitamin D. Moreover, our documentation of an M-SOB effect on EAE susceptibility in mice allows for modeling and detailed analysis of mechanisms that underlie the M-SOB effect in not only MS but in numerous other diseases in which M-SOB impacts susceptibility.-Reynolds, J. D., Case, L. K., Krementsov, D. N., Raza, A., Bartiss, R., Teuscher, C. Modeling month-season of birth as a risk factor in mouse models of chronic disease: from multiple sclerosis to autoimmune encephalomyelitis. © FASEB.

Effectiveness of applying progressive muscle relaxation technique on quality of life of patients with multiple sclerosis.

PubMed

Ghafari, Somayeh; Ahmadi, Fazlolah; Nabavi, Masoud; Anoshirvan, Kazemnejad; Memarian, Robabe; Rafatbakhsh, Mohamad

2009-08-01

To identify the effects of applying Progressive Muscle Relaxation Technique on Quality of Life of patients with multiple Sclerosis. In view of the growing caring options in Multiple Sclerosis, improvement of quality of life has become increasingly relevant as a caring intervention. Complementary therapies are widely used by multiple sclerosis patients and Progressive Muscle Relaxation Technique is a form of complementary therapies. Quasi-experimental study. Multiple Sclerosis patients (n = 66) were selected with no probability sampling then assigned to experimental and control groups (33 patients in each group). Means of data collection included: Individual Information Questionnaire, SF-8 Health Survey, Self-reported checklist. PMRT performed for 63 sessions by experimental group during two months but no intervention was done for control group. Statistical analysis was done by SPSS software. Student t-test showed that there was no significant difference between two groups in mean scores of health-related quality of life before the study but this test showed a significant difference between two groups, one and two months after intervention (p < 0.05). anova test with repeated measurements showed that there is a significant difference in mean score of whole and dimensions of health-related quality of life between two groups in three times (p < 0.05). Although this study provides modest support for the effectiveness of Progressive Muscle Relaxation Technique on quality of life of multiple sclerosis patients, further research is required to determine better methods to promote quality of life of patients suffer multiple sclerosis and other chronic disease. Progressive Muscle Relaxation Technique is practically feasible and is associated with increase of life quality of multiple sclerosis patients; so that health professionals need to update their knowledge about complementary therapies.

Adverse events after endovascular treatment of chronic cerebro-spinal venous insufficiency (CCSVI) in patients with multiple sclerosis.

PubMed

Ghezzi, A; Annovazzi, P; Amato, M P; Capello, E; Cavalla, P; Cocco, E; Falcini, M; Gallo, A; Patti, F; Perini, P; Rodegher, M E; Rovaris, M; Rottoli, M R; Comi, G

2013-06-01

Although it is debated whether chronic cerebro-spinal venous insufficiency (CCSVI) plays a role in multiple sclerosis (MS) development, many patients undergo endovascular treatment (ET) of CCSVI. A study is ongoing in Italy to evaluate the clinical outcome of ET. Severe adverse events (AEs) occurred in 15/462 subjects at a variable interval after ET: jugular thrombosis in seven patients, tetraventricular hydrocephalus, stroke, paroxysmal atrial fibrillation, status epilepticus, aspiration pneumonia, hypertension with tachicardia, or bleeding of bedsore in the remaining seven cases. One patient died because of myocardial infarction 10 weeks after ET. The risk of severe AEs related to ET for CCSVI must be carefully considered.

A qualitative investigation of lay perspectives of diagnosis and self-management strategies employed by people with progressive multiple sclerosis.

PubMed

Frost, Julia; Grose, Jane; Britten, Nicky

2017-05-01

This article explores how people with progressive multiple sclerosis give meaning to their experiences. It builds upon the self-management literature, which has captured the tension between the desire for retaining normalcy and the increasing burden of self-management associated with chronic disease progression. This repeat interview study is empirically grounded in 28 interviews with 14 people with progressive multiple sclerosis. We identified gender differences in diagnosis-seeking which impacted subsequent sense-making. Male respondents found a diagnosis of multiple sclerosis difficult to come to terms with, and an enduring sense of loss or anger could inhibit further sense-making. A diagnosis of multiple sclerosis was more difficult to obtain for women respondents, and any sense of certainty that diagnosis provided framed their subsequent sense-making strategies. The complex sequelae of multiple sclerosis require that self-management strategies are both contextual and timely, although even the most accomplished self-managers can lose their sense of self with neurodegeneration. Disease progression can be associated with suicidal ideation, suggesting the need for greater dialogue to ensure that people with multiple sclerosis are adequately supported to fulfil their quality of life at all stages of neurodegeneration. These lay perspectives emphasise the articulation of affect rather than the rendering of a medical diagnosis, although diagnosis may provide a degree of certainty in the short term. The ethos of self-management ensures people attempt to retain their sense of 'normality' and existent social roles for as long as possible, but this ethos can negate both one's ability to self-manage and the management of self.

Pharmaceutical Approval Update.

PubMed

Kaufman, Michele B

2016-10-01

Obeticholic acid (Ocaliva) for primary biliary cholangitis; sofosbuvir 400 mg/velpatasvir 100 mg (Epclusa) for chronic hepatitis C virus infection; and daclizumab (Zinbryta) for relapsing multiple sclerosis.

[Special cases of multiple sclerosis].

PubMed

Mendibe Bilbao, Mar

2014-12-01

Multiple sclerosis is a chronic disease that usually occurs in young people and affects them for the rest of their lives. Patients and their families usually have a series of doubts and questions on everyday matters and all types of situations that occur during the distinct stages of life and which can influence the course of the disease. The aim of this review is to provide specific answers to these questions. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Restless legs syndrome

MedlinePlus

... often in people with: Chronic kidney disease Diabetes Iron, magnesium, or folic acid deficiency Parkinson disease Peripheral neuropathy Pregnancy Multiple sclerosis RLS may also occur in people who: Use ...

The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis

PubMed Central

Lacerda, Eliana M.; Bowman, Erinna W.; Cliff, Jacqueline M.; Kingdon, Caroline C.; King, Elizabeth C.; Lee, Ji-Sook; Clark, Taane G.; Dockrell, Hazel M.; Riley, Eleanor M.; Curran, Hayley; Nacul, Luis

2017-01-01

The UK ME/CFS Biobank was launched in August 2011 following extensive consultation with professionals and patient representatives. The bioresource aims to enhance research on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), related to pathophysiology, biomarkers and therapeutic approaches. The cohort includes 18–60 year olds, encompassing 284 clinically-confirmed ME/CFS cases, 60 neurologist-diagnosed multiple sclerosis (MS) cases, and 135 healthy individuals. The Biobank contains blood samples, aliquoted into serum, plasma, peripheral blood mononuclear cells (PBMC), red blood cells/granulocyte pellet, whole blood, and RNA (totalling 29,863 aliquots). Extensive dataset (700 clinical and socio-demographic variables/participant) enables comprehensive phenotyping. Potential reuse is conditional to ethical approval. PMID:28649428

The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis.

PubMed

Lacerda, Eliana M; Bowman, Erinna W; Cliff, Jacqueline M; Kingdon, Caroline C; King, Elizabeth C; Lee, Ji-Sook; Clark, Taane G; Dockrell, Hazel M; Riley, Eleanor M; Curran, Hayley; Nacul, Luis

2017-01-01

The UK ME/CFS Biobank was launched in August 2011 following extensive consultation with professionals and patient representatives. The bioresource aims to enhance research on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), related to pathophysiology, biomarkers and therapeutic approaches. The cohort includes 18-60 year olds, encompassing 284 clinically-confirmed ME/CFS cases, 60 neurologist-diagnosed multiple sclerosis (MS) cases, and 135 healthy individuals. The Biobank contains blood samples, aliquoted into serum, plasma, peripheral blood mononuclear cells (PBMC), red blood cells/granulocyte pellet, whole blood, and RNA (totalling 29,863 aliquots). Extensive dataset (700 clinical and socio-demographic variables/participant) enables comprehensive phenotyping. Potential reuse is conditional to ethical approval.

Chronic Inflammatory Disease, Lifestyle and Risk of Disease

ClinicalTrials.gov

2018-04-06

Autoimmune Diseases; Inflammatory Bowel Diseases; Crohn Disease (CD); Ulcerative Colitis (UC); Arthritis, Rheumatoid (RA); Spondylarthropathies; Arthritis, Psoriatic (PsA); Psoriasis (PsO); Multiple Sclerosis (MS)

Rehabilitation and multiple sclerosis: hot topics in the preservation of physical functioning.

PubMed

Dalgas, Ulrik

2011-12-01

In a chronic and disabling disease like multiple sclerosis, rehabilitation becomes of major importance in the preservation of physical, psychological and social functioning. Approximately 80% of patients have multiple sclerosis for more than 35 years and most will develop disability at some point of their lives, emphasising the importance of rehabilitation in order to maintain quality of life. An important aspect of multiple sclerosis rehabilitation is the preservation of physical functioning. Hot topics in the rehabilitation of physical function include (1) exercise therapy, (2) robot-assisted training and (3) pharmacological interventions. Exercise therapy has for many years been a controversial issue in multiple sclerosis rehabilitation and the advice generally given to patients was not to participate in physical exercise, since it was thought to lead to a worsening of symptoms or fatigue. However, a paradigm shift is taking place and it is now increasingly acknowledged that exercise therapy is both safe and beneficial. Robot-assisted training is also attracting attention in multiple sclerosis rehabilitation. Several sophisticated commercial robots exist, but so far the number of scientific studies that have evaluated these is limited, although some promising results have been reported. Finally, recent studies have shown that certain pharmacological interventions have the potential to improve functional capacity substantially, with the potassium channel blocker fampridine being one of the most promising. This drug has been shown to improve walking ability in some patients with multiple sclerosis, associated with a reduction of patients' self-reported ambulatory disability. Rehabilitation strategies involving these different approaches, or combinations of them, may be of great use in improving everyday functioning and quality of life in patients with MS. Copyright © 2011 Elsevier B.V. All rights reserved.

Intensity ratio to improve black hole assessment in multiple sclerosis.

PubMed

Adusumilli, Gautam; Trinkaus, Kathryn; Sun, Peng; Lancia, Samantha; Viox, Jeffrey D; Wen, Jie; Naismith, Robert T; Cross, Anne H

2018-01-01

Improved imaging methods are critical to assess neurodegeneration and remyelination in multiple sclerosis. Chronic hypointensities observed on T1-weighted brain MRI, "persistent black holes," reflect severe focal tissue damage. Present measures consist of determining persistent black holes numbers and volumes, but do not quantitate severity of individual lesions. Develop a method to differentiate black and gray holes and estimate the severity of individual multiple sclerosis lesions using standard magnetic resonance imaging. 38 multiple sclerosis patients contributed images. Intensities of lesions on T1-weighted scans were assessed relative to cerebrospinal fluid intensity using commercial software. Magnetization transfer imaging, diffusion tensor imaging and clinical testing were performed to assess associations with T1w intensity-based measures. Intensity-based assessments of T1w hypointensities were reproducible and achieved > 90% concordance with expert rater determinations of "black" and "gray" holes. Intensity ratio values correlated with magnetization transfer ratios (R = 0.473) and diffusion tensor imaging metrics (R values ranging from 0.283 to -0.531) that have been associated with demyelination and axon loss. Intensity ratio values incorporated into T1w hypointensity volumes correlated with clinical measures of cognition. This method of determining the degree of hypointensity within multiple sclerosis lesions can add information to conventional imaging. Copyright © 2017 Elsevier B.V. All rights reserved.

Role of dimethyl fumarate in oxidative stress of multiple sclerosis: A review.

PubMed

Suneetha, A; Raja Rajeswari, K

2016-04-15

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS affecting both white and grey matter. Inflammation and oxidative stress are also thought to promote tissue damage in multiple sclerosis. Recent data point at an important role of anti-oxidative pathways for tissue protection in chronic MS, particularly involving the transcription factor nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2). Thus, novel therapeutics enhancing cellular resistance to free radicals could prove useful for MS treatment. Oxidative stress and anti-oxidative pathways are important players in MS pathophysiology and constitute a promising target for future MS therapy with dimethyl fumarate. The clinical utility of DMF in multiple sclerosis is being explored through phase III trials with BG-12, which is an oral therapeutic agent. Currently a wide research is going on to find out the exact mechanism of DMF, till date it is not clear. Based on strong signals of nephrotoxicity in non-humans and the theoretical risk of renal cell cancer from intracellular accumulation of fumarate, post-marketing study of a large population of patients will be necessary to fully assess the long-term safety of dimethyl fumarate. The current treatment goals are to shorten the duration and severity of relapses, prolong the time between relapses, and delay progression of disability. In this regard, dimethyl fumarate offers a promising alternative to orally administered fingolimod (GILENYA) or teriflunomide (AUBAGIO), which are currently marketed in the United States under FDA-mandated Risk Evaluation and Mitigation Strategy (REMS) programs because of serious safety concerns. More clinical experience with all three agents will be necessary to differentiate the tolerability of long-term therapy for patients diagnosed with multiple sclerosis. This write-up provides the detailed information of dimethyl fumarate in treating the neuro disease, multiple sclerosis and its mechanism involved via oxidative stress pathway. The rapid screening methods are also need to be developed to estimate DMF in biological samples to perform and proceed for further investigations. Copyright © 2016 Elsevier B.V. All rights reserved.

Potassium Channel KIR4.1 as an Immune Target in Multiple Sclerosis

PubMed Central

Srivastava, Rajneesh; Aslam, Muhammad; Kalluri, Sudhakar Reddy; Schirmer, Lucas; Buck, Dorothea; Tackenberg, Björn; Rothhammer, Veit; Chan, Andrew; Gold, Ralf; Berthele, Achim; Bennett, Jeffrey L.; Korn, Thomas; Hemmer, Bernhard

2016-01-01

BACKGROUND Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Many findings suggest that the disease has an autoimmune pathogenesis; the target of the immune response is not yet known. METHODS We screened serum IgG from persons with multiple sclerosis to identify antibodies that are capable of binding to brain tissue and observed specific binding of IgG to glial cells in a subgroup of patients. Using a proteomic approach focusing on membrane proteins, we identified the ATP-sensitive inward rectifying potassium channel KIR4.1 as the target of the IgG antibodies. We used a multifaceted validation strategy to confirm KIR4.1 as a target of the autoantibody response in multiple sclerosis and to show its potential pathogenicity in vivo. RESULTS Serum levels of antibodies to KIR4.1 were higher in persons with multiple sclerosis than in persons with other neurologic diseases and healthy donors (P<0.001 for both comparisons). We replicated this finding in two independent groups of persons with multiple sclerosis or other neurologic diseases (P<0.001 for both comparisons). Analysis of the combined data sets indicated the presence of serum antibodies to KIR4.1 in 186 of 397 persons with multiple sclerosis (46.9%), in 3 of 329 persons with other neurologic diseases (0.9%), and in none of the 59 healthy donors. These antibodies bound to the first extracellular loop of KIR4.1. Injection of KIR4.1 serum IgG into the cisternae magnae of mice led to a profound loss of KIR4.1 expression, altered expression of glial fibrillary acidic protein in astrocytes, and activation of the complement cascade at sites of KIR4.1 expression in the cerebellum. CONCLUSIONS KIR4.1 is a target of the autoantibody response in a subgroup of persons with multiple sclerosis. (Funded by the German Ministry for Education and Research and Deutsche Forschungsgemeinschaft.) PMID:22784115

In vivo modification of tRNA with an artificial nucleobase leads to full disease remission in an animal model of multiple sclerosis.

PubMed

Varghese, Sreeja; Cotter, Michelle; Chevot, Franciane; Fergus, Claire; Cunningham, Colm; Mills, Kingston H; Connon, Stephen J; Southern, John M; Kelly, Vincent P

2017-02-28

Queuine is a modified pyrrolopyrimidine nucleobase derived exclusively from bacteria. It post-transcriptionally replaces guanine 34 in transfer RNA isoacceptors for Asp, Asn, His and Tyr, in almost all eukaryotic organisms, through the activity of the ancient tRNA guanine transglycosylase (TGT) enzyme. tRNA hypomodification with queuine is a characteristic of rapidly-proliferating, non-differentiated cells. Autoimmune diseases, including multiple sclerosis, are characterised by the rapid expansion of T cells directed to self-antigens. Here, we demonstrate the potential medicinal relevance of targeting the modification of tRNA in the treatment of a chronic multiple sclerosis model—murine experimental autoimmune encephalomyelitis. Administration of a de novo designed eukaryotic TGT substrate (NPPDAG) led to an unprecedented complete reversal of clinical symptoms and a dramatic reduction of markers associated with immune hyperactivation and neuronal damage after five daily doses. TGT is essential for the therapeutic effect, since animals deficient in TGT activity were refractory to therapy. The data suggest that exploitation of the eukaryotic TGT enzyme is a promising approach for the treatment of multiple sclerosis.

Exploring barriers to remaining physically active: a case report of a person with multiple sclerosis.

PubMed

Zalewski, Kathryn

2007-03-01

Physical therapy intervention for those with chronic disabling conditions typically follows an episode of care approach: therapists provide services when a decrement in functional performance occurs such that individuals require intervention to return to baseline performance. Attention to the psychosocial supports required for successful transition can be unintentionally minimized when the focus of an episode of care follows a change in physical function. The purpose of this case report is to present and discuss the challenges to successful community reintegration following physical therapy intervention with an emphasis on developing independent exercise habits in management of a person with multiple sclerosis. RW, presented in this case study, is a 52-year-old man diagnosed with progressive multiple sclerosis five years before self-referral to a pro bono physical therapy clinic.

Expression of the Antioxidative Enzyme Peroxiredoxin 2 in Multiple Sclerosis Lesions in Relation to Inflammation

PubMed Central

Voigt, David; Scheidt, Uta; Derfuss, Tobias; Brück, Wolfgang; Junker, Andreas

2017-01-01

Multiple sclerosis is a chronic inflammatory disease of the central nervous system, characterized by demyelination and axonal damage as well as neuronal degeneration. Since oxygen-derived free radicals are an important factor leading to tissue damage in inflammatory multiple sclerosis (MS) lesions, research on antioxidative systems is essential to identify endogenous factors which can possibly counteract oxidative damage. As an important scavenging enzyme family, peroxiredoxins (PRDXs) play a crucial role in preventing oxidative damage; however little is known about their expression and function in MS lesions. In the present study we examined the expression of PRDX2 in white matter lesions of MS patients with long-standing, chronic disease. PRDX2 expression was investigated by immunohistochemistry in the context of oxidative stress and inflammation (determined by microglia/macrophage and T cell infiltration) in ten MS autopsy cases as well as seven control autopsy cases. PRDX2 was found to be upregulated in white matter MS lesions mainly in astrocytes, and its expression level was positively correlated with the degree of inflammation and oxidative stress. Our data suggest that PRDX2 expression contributes to the resistance of astrocytes against oxidative damage. PMID:28375164

Significance and In Vivo Detection of Iron-Laden Microglia in White Matter Multiple Sclerosis Lesions

PubMed Central

Gillen, Kelly M.; Mubarak, Mayyan; Nguyen, Thanh D.; Pitt, David

2018-01-01

Microglia are resident immune cells that fulfill protective and homeostatic functions in the central nervous system (CNS) but may also promote neurotoxicity in the aged brain and in chronic disease. In multiple sclerosis (MS), an autoimmune demyelinating disease of the CNS, microglia and macrophages contribute to the development of white matter lesions through myelin phagocytosis, and possibly to disease progression through diffuse activation throughout myelinated white matter. In this review, we discuss an additional compartment of myeloid cell activation in MS, i.e., the rim and normal adjacent white matter of chronic active lesions. In chronic active lesions, microglia and macrophages may contain high amounts of iron, express markers of proinflammatory polarization, are activated for an extended period of time (years), and drive chronic tissue damage. Iron-positive myeloid cells can be visualized and quantified with quantitative susceptibility mapping (QSM), a magnetic resonance imaging technique. Thus, QSM has potential as an in vivo biomarker for chronic inflammatory activity in established white matter MS lesions. Reducing chronic inflammation associated with iron accumulation using existing or novel MS therapies may impact disease severity and progression. PMID:29515576

Endovascular treatment of chronic cerebro spinal venous insufficiency in patients with multiple sclerosis modifies circulating markers of endothelial dysfunction and coagulation activation: a prospective study.

PubMed

Napolitano, Mariasanta; Bruno, Aldo; Mastrangelo, Diego; De Vizia, Marcella; Bernardo, Benedetto; Rosa, Buonagura; De Lucia, Domenico

2014-10-01

We performed a monocentric observational prospective study to evaluate coagulation activation and endothelial dysfunction parameters in patients with multiple sclerosis undergoing endovascular treatment for cerebro-spinal-venous insufficiency. Between February 2011 and July 2012, 144 endovascular procedures in 110 patients with multiple sclerosis and chronical cerebro-spinal venous insufficiency were performed and they were prospectively analyzed. Each patient was included in the study according to previously published criteria, assessed by the investigators before enrollment. Endothelial dysfunction and coagulation activation parameters were determined before the procedure and during follow-up at 1, 3, 6, 9, 12, 15 and 18 months after treatment, respectively. After the endovascular procedure, patients were treated with standard therapies, with the addition of mesoglycan. Fifty-five percent of patients experienced a favorable outcome of multiple sclerosis within 1 month after treatment, 25% regressed in the following 3 months, 24.9% did not experience any benefit. In only 0.1% patients, acute recurrence was observed and it was treated with high-dose immunosuppressive therapy. No major complications were observed. Coagulation activation and endothelial dysfunction parameters were shown to be reduced at 1 month and stable up to 12-month follow-up, and they were furthermore associated with a good clinical outcome. Endovascular procedures performed by a qualified staff are well tolerated; they can be associated with other currently adopted treatments. Correlations between inflammation, coagulation activation and neurodegenerative disorders are here supported by the observed variations in plasma levels of markers of coagulation activation and endothelial dysfunction.

Role of Proangiogenic Factors in Immunopathogenesis of Multiple Sclerosis.

PubMed

Hamid, Kabir Magaji; Mirshafiey, Abbas

2016-02-01

Angiogenesis is a complex and balanced process in which new blood vessels form from preexisting ones by sprouting, splitting, growth and remodeling. This phenomenon plays a vital role in many physiological and pathological processes. However, the disturbance in physiological process can play a role in pathogenesis of some chronic inflammatory diseases, including multiple sclerosis (MS) in human and its animal model. Although the relation between abnormal blood vessels and MS lesions was established in previous studies, but the role of pathological angiogenesis remains unclear. In this study, the link between proangiogenic factors and multiple sclerosis pathogenesis was examined by conducting a systemic review. Thus we searched the English medical literature via PubMed, ISI web of knowledge, Medline and virtual health library (VHL) databases. In this review, we describe direct and indirect roles of some proangiogenic factors in MS pathogenesis and report the association of these factors with pathological and inflammatory angiogenesis.

The meaning of women's experiences of living with multiple sclerosis.

PubMed

Olsson, Malin; Lexell, Jan; Söderberg, Siv

2008-04-01

We conducted a qualitative inquiry in order to describe the meaning of women's experiences of living with multiple sclerosis (MS). Multiple sclerosis is a chronic autoimmune disease of the central nervous system. The majority of persons living with MS are women. Living with MS has been described as difficult because of the uncertainty of the illness. Ten women with MS were interviewed and the interviews were analyzed with a phenomenological hermeneutic interpretation. In this study, we suggest that the meaning of living with MS for women can be understood as trying to maintain power and living with an unrecognizable body. The bodies of women with MS serve as hindrances in everyday life. Bodily changes evident to others impose feelings of being met in a different way, which can be understood as an expression of a violated dignity. At the same time, the women with MS struggle to protect their dignity.

A Comparison of Self-Hypnosis Versus Progressive Muscle Relaxation in Patients With Multiple Sclerosis and Chronic Pain1

PubMed Central

Jensen, Mark P.; Barber, Joseph; Romano, Joan M.; Molton, Ivan R.; Raichle, Katherine A.; Osborne, Travis L.; Engel, Joyce M.; Stoelb, Brenda L.; Kraft, George H.; Patterson, David R.

2009-01-01

Twenty-two patients with multiple sclerosis (MS) and chronic pain we recruited into a quasi-experimental trial comparing the effects of self-hypnosis training (HYP) with progressive muscle relaxation (PMR) on pain intensity and pain interference; 8 received HYP and the remaining 14 participants were randomly assigned to receive either HYP or PMR. HYP-condition participants reported significantly greater pre- to postsession as well as pre- to posttreatment decreases in pain and pain interference than PMR-condition participants, and gains were maintained at 3-month follow-up. Most of the participants in both conditions reported that they continued to use the skills they learned in treatment and experienced pain relief when they did so. General hypnotizability was not significantly related to treatment outcome, but treatment-outcome expectancy assessed before and after the first session was. The results support the efficacy of self-hypnosis training for the management of chronic pain in persons with MS. PMID:19234967

Precision medicine in chronic disease management: The multiple sclerosis BioScreen.

PubMed

Gourraud, Pierre-Antoine; Henry, Roland G; Cree, Bruce A C; Crane, Jason C; Lizee, Antoine; Olson, Marram P; Santaniello, Adam V; Datta, Esha; Zhu, Alyssa H; Bevan, Carolyn J; Gelfand, Jeffrey M; Graves, Jennifer S; Goodin, Douglas S; Green, Ari J; von Büdingen, H-Christian; Waubant, Emmanuelle; Zamvil, Scott S; Crabtree-Hartman, Elizabeth; Nelson, Sarah; Baranzini, Sergio E; Hauser, Stephen L

2014-11-01

We present a precision medicine application developed for multiple sclerosis (MS): the MS BioScreen. This new tool addresses the challenges of dynamic management of a complex chronic disease; the interaction of clinicians and patients with such a tool illustrates the extent to which translational digital medicine-that is, the application of information technology to medicine-has the potential to radically transform medical practice. We introduce 3 key evolutionary phases in displaying data to health care providers, patients, and researchers: visualization (accessing data), contextualization (understanding the data), and actionable interpretation (real-time use of the data to assist decision making). Together, these form the stepping stones that are expected to accelerate standardization of data across platforms, promote evidence-based medicine, support shared decision making, and ultimately lead to improved outcomes. © 2014 American Neurological Association.

[Medical and social condition of families of patients with multiple sclerosis].

PubMed

Lugovtsova, Y A; Karnaukh, V N

2015-01-01

To analyze the medical and social condition of 70 families having a member with multiple sclerosis of working age. We used the classification of types and kinds of families of chronically ill patients of working-age that included two sections - grouping families by health and social status. By medical condition, most families are assessed as dysfunctional II degree, by welfare as at risk families. Both health and social status of the family depends on a number of social factors as well as the clinical characteristics of the disease, in particular, type of disease course and severity of neurological deficit.

Multiple Sclerosis: Epidemiologic, Clinical, and Therapeutic Aspects.

PubMed

Vidal-Jordana, Angela; Montalban, Xavier

2017-05-01

Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system that affects young people. MS develops in genetically susceptible individuals exposed to different unknown triggering factors. Different phenotypes are described. About 15% of patients present with a primary progressive course and 85% with a relapsing-remitting course. An increasing number of disease-modifying treatments has emerged. Although encouraging, the number of drugs challenges the neurologist because each treatment has its own risk-benefit profile. Patients should be involved in the decision-making process to ensure good treatment and safety monitoring adherence. Copyright © 2016 Elsevier Inc. All rights reserved.

Multiple sclerosis.

PubMed

Files, Daniel Kane; Jausurawong, Tani; Katrajian, Ruba; Danoff, Robert

2015-06-01

Multiple sclerosis (MS) is a chronic, debilitating disease that can have devastating effects. Presentation varies widely in symptoms, pace, and progression. In addition to a thorough history and physical examination, diagnostic tools required to diagnose MS and exclude other diagnoses include MRI, evoked potential testing, and cerebrospinal fluid analysis. Although the disease is not curable presently, quality of life can be improved by minimizing the frequency and severity of disease burden. Disease modification, symptom management, preservation of function, and treatment of psychosocial issues are paramount to enhance the quality of life for the patient affected with MS. Copyright © 2015 Elsevier Inc. All rights reserved.

Physical activity motivation and benefits in people with multiple sclerosis.

PubMed

Fasczewski, Kimberly S; Gill, Diane L; Rothberger, Sara M

2018-06-01

Multiple sclerosis is a degenerative neurological disease that affects 2.1 million people worldwide. There is no cure, but an expanding body of research supports the positive impact of physical activity and suggests physical activity has benefits for the individual's psychological and physical well-being. Using Self-Determination Theory as a framework, mixed methods with a focus on qualitative interviews were used to explore physical activity motivation and benefits with a sample of highly active people with multiple sclerosis (n = 15). Disability level ranged from not disabled to wheelchair bound with the majority of participants reporting minimal impact from multiple sclerosis. Survey data were collected using a number of open-ended questions along with measures of self-efficacy, self-determined motivation, physical activity, and quality of life. Additionally, eight individuals participated in semistructured telephone interviews focused on (a) motivation and strategies used to maintain physical activity and (b) the benefits and impact of physical activity in their lives. The main findings were consistent with Self-Determination Theory; participants described feelings of accomplishment and competence in both their physical activity and daily life, as well as a sense of independence and autonomy. Similarly, all participants cited benefits, and the main themes were enhanced satisfaction with life and an overall positive outlook on life. Results provide insight into the role of physical activity in a highly active sample and have implications for professionals working in physical activity settings with the multiple sclerosis population. Interventions aimed at increasing long-term physical activity adherence should focus on increasing autonomy and competence for physical activity in the individual and promoting potential increased quality of life outcomes from physical activity participation. Implications for Rehabilitation Multiple sclerosis is a chronic degenerative neurological disease that the individual lives with for a majority of the lifespan. Physical activity is one means that has been shown to aid is the control of multiple sclerosis symptoms. Increasing patient understanding of the benefits of using physical activity as a means to control multiple sclerosis symptoms may result in long-term physical activity adherence. Physical activity interventions that develop feelings of competence and independent choice in the patient may be more successful for long-term participation.

[Consensus document on spasticity in patients with multiple sclerosis. Grupo de Enfermedades Desmielinizantes de la Sociedad Española de Neurología].

PubMed

Oreja-Guevara, Celia; Montalban, Xavier; de Andrés, Clara; Casanova-Estruch, Bonaventura; Muñoz-García, Delicias; García, Inmaculada; Fernández, Óscar

2013-10-16

Multiple sclerosis is a chronic neurological inflammatory demyelinating disease. Specialists involved in the symptomatic treatment of this disease tend to apply heterogeneous diagnostic and treatment criteria. To establish homogeneous criteria for treating spasticity based on available scientific knowledge, facilitating decision-making in regular clinical practice. A group of multiple sclerosis specialists from the Spanish Neurological Society demyelinating diseases working group met to review aspects related to spasticity in this disease and draw up the consensus. After an exhaustive bibliographic search and following a metaplan technique, a number of preliminary recommendations were established to incorporate into the document. Finally, each argument was classified depending on the degree of recommendation according to the SIGN (Scottish Intercollegiate Guidelines Network) system. The resulting text was submitted for review by the demyelinating disease group. An experts' consensus was reached regarding spasticity triggering factors, related symptoms, diagnostic criteria, assessment methods, quality of life and therapeutic management (drug and non-drug) criteria. The recommendations included in this consensus can be a useful tool for improving the quality of life of multiple sclerosis patients, as they enable improved diagnosis and treatment of spasticity.

Application of laser radiation and magnetostimulation in therapy of patients with multiple sclerosis.

PubMed

Kubsik, Anna; Klimkiewicz, Robert; Janczewska, Katarzyna; Klimkiewicz, Paulina; Jankowska, Agnieszka; Woldańska-Okońska, Marta

2016-01-01

Multiple sclerosis is one of the most common neurological disorders. It is a chronic inflammatory demyelinating disease of the CNS, whose etiology is not fully understood. Application of new rehabilitation methods are essential to improve functional status. The material studied consisted of 120 patients of both sexes (82 women and 38 men) aged 21-81 years. The study involved patients with a diagnosis of multiple sclerosis. The aim of the study was to evaluate the effect of laser radiation and other therapies on the functional status of patients with multiple sclerosis. Patients were randomly divided into four treatment groups. The evaluation was performed three times - before the start of rehabilitation, immediately after rehabilitation (21 days of treatment) and subsequent control - 30 days after the patients leave the clinic. The following tests were performed for all patients to assess functional status: Expanded Disability Status Scale (EDSS) of Kurtzke and Barthel Index. Results of all testing procedures show that the treatment methods are improving the functional status of patients with multiple sclerosis, with the significant advantage of the synergistic action of laser and magneto stimulation. The combination of laser and magneto stimulation significantly confirmed beneficial effect on quality of life. The results of these studies present new scientific value and are improved compared to program of rehabilitation of patients with multiple sclerosis by laser radiation which was previously used. This study showed that synergic action of laser radiation and magneto stimulation has a beneficial effect on improving functional status, and thus improves the quality of life of patients with multiple sclerosis. The effects of all methods of rehabilitation are persisted after cessation of treatment applications, with a particular advantage of the synergistic action of laser radiation and magneto stimulation, which indicates the possibility to elicitation in these methods the phenomenon of the biological hysteresis.

The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn's Disease, and Other Chronic Pain Disorders.

PubMed

Patten, Denise K; Schultz, Bob G; Berlau, Daniel J

2018-03-01

Chronic inflammatory diseases are complex to treat and have an impact on a large number of patients. Due to the difficulty of treating these diseases and the great impact on quality of life, patients often seek off-label, complimentary, or alternative medicines to gain relief from symptoms. Low-dose naltrexone has been used off-label for treatment of pain and inflammation in multiple sclerosis, Crohn's disease, fibromyalgia, and other diseases. Naltrexone is a mu-opioid receptor antagonist indicated by the U.S. Food and Drug Administration for opioid and alcohol dependence. It is hypothesized that lower than standard doses of naltrexone inhibit cellular proliferation of T and B cells and block Toll-like receptor 4, resulting in an analgesic and antiinflammatory effect. It is the purpose of this review to examine the evidence of the safety, tolerability, and efficacy of low-dose naltrexone for use in chronic pain and inflammatory conditions. Currently, evidence supports the safety and tolerability of low-dose naltrexone in multiple sclerosis, fibromyalgia, and Crohn's disease. Fewer studies support the efficacy of low-dose naltrexone, with most of these focusing on subjective measures such as quality of life or self-reported pain. These studies do demonstrate that low-dose naltrexone has subjective benefits over placebo, but evidence for more objective measures is limited. However, further randomized controlled trials are needed to determine the efficacy of low-dose naltrexone due to insufficient evidence supporting its use in these disease states. This review provides practitioners with the extent of low-dose naltrexone evidence so that they can be cognizant of situations where it may not be the most appropriate therapy. © 2018 Pharmacotherapy Publications, Inc.

Contingent interaction during work and play tasks for mothers with multiple sclerosis and their daughters.

PubMed

Crist, P

1993-02-01

Occupational therapy has focused on activity as a catalyst for understanding human roles and interactions, regardless of whether disability or chronic illness is present. Parenting is an important interactional activity accompanied by specific role expectations. This investigation examined the interaction patterns of mothers with multiple sclerosis and their daughters. Thirty-one mothers with multiple sclerosis and their daughters aged 8 to 12 years were compared with 34 mothers without disabilities and their daughters aged 8 to 12 years. Videotaped mother-daughter interactions during a work task and a play task were scored by two raters for 11 different behaviors. These behaviors were collapsed into three behavioral composites--receptiveness, directiveness, and dissuasiveness--for statistical analysis. Statistical analysis revealed no significant differences between the two groups on the behavioral composites for either mothers or their daughters. The two tasks stimulated a different pattern of mother-daughter interactions. For both members of the dyad, interactions during the work task were more directive and less dissuasive than those in the play task. The clinical implication of this finding indicates the importance of understanding the influence of the task selected when observing interaction. Because of recent social and legal changes, understanding parenting and chronic illness is critical.

The role of information system in multiple sclerosis management

PubMed Central

Ajami, Sima; Ahmadi, Golchehreh; Etemadifar, Masoud

2014-01-01

Multiple sclerosis (MS) is a chronic disease of central nervous system. The multiple sclerosis information system (MSIS), such as other information system (IS), depends on identification, collection and processing of data for producing useful information. Lack of the integrated IS for collecting standard data causes undesirable effects on exchanging, comparing, and managing. The aim of this study was to recognize the role of the IS in the MS management and determine the advantages and barriers in implementing of the MSIS. The present study was a nonsystematized review that was done in order to recognize the role of the IS in the MS management. In this study, electronic scientific resources such as scientific magazines and books and published topics at conferences were used. We used key words (IS, chronic disease management, and multiple sclerosis), their combination or their synonyms in title, key words, abstracts, and text of English articles and published reports from 1980 until 2013, and by using search engines such as Google, Google Scholar and scientific databases and electronic issues such as iPubMed, sufficiently important difference, Scopus, Medlib, and Magiran for gathering information. More than 200 articles and reports were collected and assessed and 139 of them. Findings showed that the MSIS can reduce of disease expenses through continuously collecting correct, accurate, sufficient, and timely patients and disease nature information; recoding; editing; processing; exchanging, and distributing among different health care centers. Although the MSIS has many advantages; but, we cannot ignore cultural, economic, technical, organizational, and managerial barriers. Therefore, it is necessary to do studies for preventing, reducing, and controlling them. One of the ways is to recognize the advantages of the MSIS and usage information technology in optimizing disease management. PMID:25709660

The role of information system in multiple sclerosis management.

PubMed

Ajami, Sima; Ahmadi, Golchehreh; Etemadifar, Masoud

2014-12-01

Multiple sclerosis (MS) is a chronic disease of central nervous system. The multiple sclerosis information system (MSIS), such as other information system (IS), depends on identification, collection and processing of data for producing useful information. Lack of the integrated IS for collecting standard data causes undesirable effects on exchanging, comparing, and managing. The aim of this study was to recognize the role of the IS in the MS management and determine the advantages and barriers in implementing of the MSIS. The present study was a nonsystematized review that was done in order to recognize the role of the IS in the MS management. In this study, electronic scientific resources such as scientific magazines and books and published topics at conferences were used. We used key words (IS, chronic disease management, and multiple sclerosis), their combination or their synonyms in title, key words, abstracts, and text of English articles and published reports from 1980 until 2013, and by using search engines such as Google, Google Scholar and scientific databases and electronic issues such as iPubMed, sufficiently important difference, Scopus, Medlib, and Magiran for gathering information. More than 200 articles and reports were collected and assessed and 139 of them. Findings showed that the MSIS can reduce of disease expenses through continuously collecting correct, accurate, sufficient, and timely patients and disease nature information; recoding; editing; processing; exchanging, and distributing among different health care centers. Although the MSIS has many advantages; but, we cannot ignore cultural, economic, technical, organizational, and managerial barriers. Therefore, it is necessary to do studies for preventing, reducing, and controlling them. One of the ways is to recognize the advantages of the MSIS and usage information technology in optimizing disease management.

The presence and meaning of chronic sorrow in patients with multiple sclerosis.

PubMed

Isaksson, Ann-Kristin; Gunnarsson, Lars-Gunnar; Ahlström, Gerd

2007-11-01

The aim of this study was to explore the presence and meaning of chronic sorrow and the presence of depression in a fairly large group of persons with multiple sclerosis (MS). MS is a chronic and progressive neurological disease with a variety of symptoms. The patients have to live with losses of different kinds. A few earlier studies have used the concept of chronic sorrow to illustrate the emotional situation of such patients. Sixty-one patients were interviewed about the occurrence of chronic sorrow and, thereafter, screened for depression. Thirty-eight (62%) of them fulfilled the criteria for chronic sorrow. The interviews were analysed with latent content analysis. Seven themes describe the losses that caused sorrow: loss of hope, loss of control over the body, loss of integrity and dignity, loss of a healthy identity, loss of faith that life is just, loss of social relations and loss of freedom. The sorrow was constantly present or periodically overwhelming. Only four of the 38 patients with chronic sorrow had symptoms of being mildly depressed. Chronic sorrow meant loss of hope, of control over the body, of integrity and of identity. The concept of chronic sorrow complements that of depression in providing important new knowledge relevant to understanding the consequences MS can have for the individual. Knowledge of the meaning of chronic sorrow can contribute to the nurse's ability to give psychological support and promote a sense of hope and control in the MS patient.

Therapeutic Approach to the Management of Pediatric Demyelinating Disease: Multiple Sclerosis and Acute Disseminated Encephalomyelitis.

PubMed

Brenton, J Nicholas; Banwell, Brenda L

2016-01-01

Acquired pediatric demyelinating diseases manifest acutely with optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, or with various other acute deficits in focal or polyfocal areas of the central nervous system. Patients may experience a monophasic illness (as in the case of acute disseminated encephalomyelitis) or one that may manifest as a chronic, relapsing disease [e.g., multiple sclerosis (MS)]. The diagnosis of pediatric MS and other demyelinating disorders of childhood has been facilitated by consensus statements regarding diagnostic definitions. Treatment of pediatric MS has been modeled after data obtained from clinical trials in adult-onset MS. There are now an increasing number of new therapeutic agents for MS, and many will be formally studied for use in pediatric patients. There are important efficacy and safety concerns regarding the use of these therapies in children and young adults. This review will discuss acute management as well as chronic immunotherapies in acquired pediatric demyelination.

Evolution in quality of life and epidemiological impact after endovascular treatment of chronic cerebro-spinal venous insufficiency in patients with multiple sclerosis.

PubMed

Beelen, R; Maene, L; Castenmiller, P; Decoene, V; Degrieck, I

2012-03-01

We report the outcome of 67 patients after endovascular treatment of chronic cerebro-spinal venous insufficiency in patients with multiple sclerosis. Material and methods For evaluating outcome, patients were divided into three groups with respective outcome after three, six and twelve months. Assessment of outcome was done by a disease-specific quality-of-life score that reflects the physical health (physical health composite, PHC) and mental health (mental health composite, MHC) by a score. Improvement in PHC was significant (P < 0.05) in the three- and six-month groups. Improvement in MHC was only significant (P < 0.05) in the three-month group. In conclusion, we can state that the result of endovascular treatment seems to decay although the baseline is still higher than preoperative. To confirm this finding, this study needs to be reproduced in a larger patient population.

Chronic cerebro-spinal venous insufficiency (CCSVI) and multiple sclerosis.

PubMed

Ghezzi, A; Comi, G; Federico, A

2011-02-01

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS caused by the interplay of genetic and environmental factors. In the last years, it has been suggested that an abnormal venous drainage due to stenosis or malformation of the internal jugular and/or azygous veins may play a major pathogenetic role in MS. This abnormality called chronic cerebro-spinal venous insufficiency (CCSVI) could result in increased permeability of blood brain barrier, local iron deposition and secondary multifocal inflammation. In the present paper, literature data in favour and against this hypothesis are reported. A great variability of CCSVI has been found in both MS patients (ranging from 0 to 100%) and in control subjects (from 0 to 23%). This large variability is explained by methodological aspects, problems in assessing CCSVI, and differences among clinical series. It is urgent to perform appropriate epidemiological studies to define the possible relationship between CCSVI and MS.

Efficacy of transcutaneous electrical nerve stimulation (tens) for chronic low-back pain in a multiple sclerosis population: a randomized, placebo-controlled clinical trial.

PubMed

Warke, Kim; Al-Smadi, Jamal; Baxter, David; Walsh, Deirdre M; Lowe-Strong, Andrea S

2006-01-01

This study was designed to investigate the hypoalgesic effects of self-applied transcutaneous electrical nerve stimulation (TENS) on chronic low-back pain (LBP) in a multiple sclerosis (MS) population. Ninety participants with probable or definite MS (aged 21 to 78 y) presenting with chronic LBP were recruited and randomized into 3 groups (n=30 per group): (1) low-frequency TENS group (4 Hz, 200 micros); (2) high-frequency TENS group (110 Hz, 200 micros); and (3) placebo TENS. Participants self-applied TENS for 45 minutes, a minimum of twice daily, for 6 weeks. Outcome measures were recorded at weeks 1, 6, 10, and 32. Primary outcome measures included: Visual Analog Scale for average LBP and the McGill Pain Questionnaire. Secondary outcome measures included: Visual Analog Scale for worst and weekly LBP, back and leg spasm; Roland Morris Disability Questionnaire; Barthel Index; Rivermead Mobility Index; Multiple Sclerosis Quality of Life-54 Instrument, and a daily logbook. Data were analyzed blind using parametric and nonparametric tests, as appropriate. Results indicated a statistically significant interactive effect between groups for average LBP (P=0.008); 1-way analysis of covariance did not show any significant effects at any time point once a Bonferonni correction was applied (P>0.05). However, clinically important differences were observed in some of the outcome measures in both active treatment groups during the treatment and follow-up periods. Although not statistically significant, the observed effects may have implications for the clinical prescription and the use of TENS within this population.

Clustering Multiple Sclerosis Subgroups with Multifractal Methods and Self-Organizing Map Algorithm

NASA Astrophysics Data System (ADS)

Karaca, Yeliz; Cattani, Carlo

Magnetic resonance imaging (MRI) is the most sensitive method to detect chronic nervous system diseases such as multiple sclerosis (MS). In this paper, Brownian motion Hölder regularity functions (polynomial, periodic (sine), exponential) for 2D image, such as multifractal methods were applied to MR brain images, aiming to easily identify distressed regions, in MS patients. With these regions, we have proposed an MS classification based on the multifractal method by using the Self-Organizing Map (SOM) algorithm. Thus, we obtained a cluster analysis by identifying pixels from distressed regions in MR images through multifractal methods and by diagnosing subgroups of MS patients through artificial neural networks.

The endocannabinoid system and its therapeutic exploitation in multiple sclerosis: Clues for other neuroinflammatory diseases.

PubMed

Chiurchiù, Valerio; van der Stelt, Mario; Centonze, Diego; Maccarrone, Mauro

2018-01-01

Multiple sclerosis is the most common inflammatory demyelinating disease of the central nervous system, caused by an autoimmune response against myelin that eventually leads to progressive neurodegeneration and disability. Although the knowledge on its underlying neurobiological mechanisms has considerably improved, there is a still unmet need for new treatment options, especially for the progressive forms of the disease. Both preclinical and clinical data suggest that cannabinoids, derived from the Cannabis sativa plant, may be used to control symptoms such as spasticity and chronic pain, whereas only preclinical data indicate that these compounds and their endogenous counterparts, i.e. the endocannabinoids, may also exert neuroprotective effects and slow down disease progression. Here, we review the preclinical and clinical studies that could explain the therapeutic action of cannabinoid-based medicines, as well as the medical potential of modulating endocannabinoid signaling in multiple sclerosis, with a link to other neuroinflammatory disorders that share common hallmarks and pathogenetic features. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Multiple sclerosis pathways: an innovative nursing role in disease management.

PubMed

Madonna, M G; Keating, M M

1999-12-01

Multiple sclerosis (MS), a chronic disease of the central nervous system, is characterized by a variable and unpredictable course. The most common pattern of the disease is the relapsing-remitting form in which clearly defined relapses (also called exacerbations) are followed by complete or incomplete recovery. Interferon beta-1b (Betaseron), a drug that affects the natural course of the disease, was developed for the treatment of relapsing-remitting MS. Multiple Sclerosis Pathways (MSP), a disease management program, was developed to provide comprehensive and personal support to MS patients taking interferon beta-1b and to serve as an information resource for all people with MS, their families, and healthcare professionals. The MSP program includes personal patient assistance, reimbursement services, a 24-hour nurse hotline, training program, educational resources, and injection supplies. The nurse hotline counselor (NHC) utilizes the nursing process in a unique telephone nursing practice in this program. The positive impact of education and support on adherence to therapy has been validated by training and nurse hotline data.

Vestibular evoked myogenic potential findings in multiple sclerosis.

PubMed

Escorihuela García, Vicente; Llópez Carratalá, Ignacio; Orts Alborch, Miguel; Marco Algarra, Jaime

2013-01-01

Multiple sclerosis is an inflammatory disease involving the occurrence of demyelinating, chronic neurodegenerative lesions in the central nervous system. We studied vestibular evoked myogenic potentials (VEMPs) in this pathology, to allow us to evaluate the saccule, inferior vestibular nerve and vestibular-spinal pathway non-invasively. There were 23 patients diagnosed with multiple sclerosis who underwent VEMP recordings, comparing our results with a control group consisting of 35 healthy subjects. We registered p13 and n23 wave latencies, interaural amplitude difference and asymmetry ratio between both ears. Subjects also underwent an otoscopy and audiometric examination. The prolongation of p13 and n23 wave latencies was the most notable characteristic, with a mean p13 wave latency of 19.53 milliseconds and a mean latency of 30.06 milliseconds for n23. In contrast, the asymmetry index showed no significant differences with our control group. In case of multiple sclerosis, the prolongation of the p13 and n23 VEMP wave latencies is a feature that has been attributed to slowing of conduction by demyelination of the vestibular-spinal pathway. In this regard, alteration of the response or lack thereof in these potentials has a locator value of injury to the lower brainstem. Copyright © 2013 Elsevier España, S.L. All rights reserved.

The topograpy of demyelination and neurodegeneration in the multiple sclerosis brain

PubMed Central

Haider, Lukas; Hametner, Simon; Höftberger, Romana; Bagnato, Francesca; Grabner, Günther; Trattnig, Siegfried; Pfeifenbring, Sabine; Brück, Wolfgang

2016-01-01

Abstract Multiple sclerosis is a chronic inflammatory disease with primary demyelination and neurodegeneration in the central nervous system. In our study we analysed demyelination and neurodegeneration in a large series of multiple sclerosis brains and provide a map that displays the frequency of different brain areas to be affected by these processes. Demyelination in the cerebral cortex was related to inflammatory infiltrates in the meninges, which was pronounced in invaginations of the brain surface (sulci) and possibly promoted by low flow of the cerebrospinal fluid in these areas. Focal demyelinated lesions in the white matter occurred at sites with high venous density and additionally accumulated in watershed areas of low arterial blood supply. Two different patterns of neurodegeneration in the cortex were identified: oxidative injury of cortical neurons and retrograde neurodegeneration due to axonal injury in the white matter. While oxidative injury was related to the inflammatory process in the meninges and pronounced in actively demyelinating cortical lesions, retrograde degeneration was mainly related to demyelinated lesions and axonal loss in the white matter. Our data show that accumulation of lesions and neurodegeneration in the multiple sclerosis brain does not affect all brain regions equally and provides the pathological basis for the selection of brain areas for monitoring regional injury and atrophy development in future magnetic resonance imaging studies. PMID:26912645

Demographic, socioeconomic and clinical correlates of self-management in multiple sclerosis.

PubMed

Wilski, Maciej; Tasiemski, Tomasz; Kocur, Piotr

2015-01-01

Our aim was to identify demographic, clinical and socioeconomic predictors of self-management in multiple sclerosis (MS). The study was performed on a group of 283 patients with multiple sclerosis who completed Multiple Sclerosis Self-Management Scale - Revised (MSSM-R), Multiple Sclerosis Impact Scale (MSIS-29), Actually Received Support Scale (part of Berlin Social Support Scale), Expanded Disability Status Scale (EDSS) and Socioeconomic resources scale. Patients were recruited through cooperation with Multiple Sclerosis Rehabilitation Centre in Borne Sulinowo and Polish Society of Multiple Sclerosis. Demographic and illness-related problems were determined with self-report survey. The group consisted of 185 women and 98 men, with a mean age of 48 years. The level of disability and disease severity varied, mean time elapsed since MS diagnosis was 13 years. The final predictive model of self-management in MS was based on two main predictors: received support and available socioeconomic resources. Patients with MS who received adequate support from the closest relatives (R(2 )= 0.07, F(1, 279) = 21.84, p ≤ 0.01) and had larger available socioeconomic resources (R(2) = 0.11, F(2, 278) = 17.06, p ≤ 0.01), turned out to be the most effective in self-management. Moreover, a relationship between self-management in MS and gender as well as monthly income attributable to one family member was documented. We identified a group of MS patients who are at an increased risk of poor self-management and therefore require more attention from medical staff. This group includes patients with low level of received support, low socioeconomic resources and to a lesser degree men, and also persons receiving low monthly income. Implications for Rehabilitation Self-management of chronic illness is a key component of active participation in rehabilitation process. Low self-management in multiple sclerosis (MS) is considered to be one of the most important factors contributing to low rehabilitation efficacy, more severe long-term complications and increase in healthcare costs. Knowledge on predictors of self-management should be used in clinical practice when providing treatment, support, education and rehabilitation for patients with MS. Increasing support and improving social conditions are potentially important targets for interventions aimed at optimization of self-management, and thereby reduction of health care costs and improvement of health.

The development of a disease oriented eFolder for multiple sclerosis decision support

NASA Astrophysics Data System (ADS)

Ma, Kevin; Jacobs, Colin; Fernandez, James; Amezcua, Lilyana; Liu, Brent

2010-03-01

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. The chronic nature of MS necessitates multiple MRI studies to track disease progression. Currently, MRI assessment of multiple sclerosis requires manual lesion measurement and yields an estimate of lesion volume and change that is highly variable and user-dependent. In the setting of a longitudinal study, disease trends and changes become difficult to extrapolate from the lesions. In addition, it is difficult to establish a correlation between these imaged lesions and clinical factors such as treatment course. To address these clinical needs, an MS specific e-Folder for decision support in the evaluation and assessment of MS has been developed. An e-Folder is a disease-centric electronic medical record in contrast to a patient-centric electronic health record. Along with an MS lesion computer aided detection (CAD) package for lesion load, location, and volume, clinical parameters such as patient demographics, disease history, clinical course, and treatment history are incorporated to make the e-Folder comprehensive. With the integration of MRI studies together with related clinical data and informatics tools designed for monitoring multiple sclerosis, it provides a platform to improve the detection of treatment response in patients with MS. The design and deployment of MS e-Folder aims to standardize MS lesion data and disease progression to aid in decision making and MS-related research.

CD8+ T Cells Cause Disability and Axon Loss in a Mouse Model of Multiple Sclerosis

PubMed Central

Schmalstieg, William F.; Sauer, Brian M.; Wang, Huan; German, Christopher L.; Windebank, Anthony J.; Rodriguez, Moses; Howe, Charles L.

2010-01-01

Background The objective of this study was to test the hypothesis that CD8+ T cells directly mediate motor disability and axon injury in the demyelinated central nervous system. We have previously observed that genetic deletion of the CD8+ T cell effector molecule perforin leads to preservation of motor function and preservation of spinal axons in chronically demyelinated mice. Methodology/Principal Findings To determine if CD8+ T cells are necessary and sufficient to directly injure demyelinated axons, we adoptively transferred purified perforin-competent CD8+ spinal cord-infiltrating T cells into profoundly demyelinated but functionally preserved perforin-deficient host mice. Transfer of CD8+ spinal cord-infiltrating T cells rapidly and irreversibly impaired motor function, disrupted spinal cord motor conduction, and reduced the number of medium- and large-caliber spinal axons. Likewise, immunodepletion of CD8+ T cells from chronically demyelinated wildtype mice preserved motor function and limited axon loss without altering other disease parameters. Conclusions/Significance In multiple sclerosis patients, CD8+ T cells outnumber CD4+ T cells in active lesions and the number of CD8+ T cells correlates with the extent of ongoing axon injury and functional disability. Our findings suggest that CD8+ T cells may directly injure demyelinated axons and are therefore a viable therapeutic target to protect axons and motor function in patients with multiple sclerosis. PMID:20814579

Sacral neuromodulation for the treatment of neurogenic lower urinary tract dysfunction caused by multiple sclerosis: a single-centre prospective series.

PubMed

Engeler, Daniel S; Meyer, Daniel; Abt, Dominik; Müller, Stefanie; Schmid, Hans-Peter

2015-10-23

Sacral neuromodulation is well established in the treatment of refractory, non-neurogenic lower urinary tract dysfunction, but its efficacy and safety in patients with lower urinary tract dysfunction of neurological origin is unclear. Only few case series have been reported for multiple sclerosis. We prospectively evaluated the efficacy and safety of sacral neuromodulation in patients with multiple sclerosis. Seventeen patients (13 women, 4 men) treated with sacral neuromodulation for refractory neurogenic lower urinary tract dysfunction caused by multiple sclerosis were prospectively enrolled (2007-2011). Patients had to have stable disease and confirmed neurogenic lower urinary tract dysfunction. Voiding variables, adverse events, and subjective satisfaction were assessed. Sixteen (94 %) patients had a positive test phase with a >70 % improvement. After implantation of the pulse generator (InterStim II), the improvement in voiding variables persisted. At 3 years, the median voided volume had improved significantly from 125 (range 0 to 350) to 265 ml (range 200 to 350) (p < 0.001), the post void residual from 170 (range 0 to 730) to 25 ml (range 0 to 300) (p = 0.01), micturition frequency from 12 (range 6 to 20) to 7 (range 4 to 12) (p = 0.003), and number of incontinence episodes from 3 (range 0 to 10) to 0 (range 0 to 1) (p = 0.006). The median subjective degree of satisfaction was 80 %. Only two patients developed lack of benefit. No major complications occurred. Chronic sacral neuromodulation promises to be an effective and safe treatment of refractory neurogenic lower urinary tract dysfunction in selected patients with multiple sclerosis.

Acute symptomatic sinus bradycardia in a woman treated with pulse dose steroids for multiple sclerosis: a case report.

PubMed

Kundu, Amartya; Fitzgibbons, Timothy P

2015-09-24

Sinus bradycardia has been reported after administration of pulse dose steroids, although most cases have occurred in children and are asymptomatic. We report a case of acute symptomatic sinus bradycardia due to pulse dose steroids in a woman with multiple sclerosis. Interestingly, this patient also suffered from inappropriate sinus tachycardia due to autonomic involvement of multiple sclerosis. A 48-year-old Caucasian woman with multiple sclerosis and chronic palpitations due to inappropriate sinus tachycardia was prescribed a 5-day course of intravenous methylprednisolone for treatment of an acute flare. Immediately following the fourth dose of intravenous methylprednisolone, she developed dyspnea, chest heaviness, and lightheadedness. She was referred to the emergency department where an electrocardiogram showed marked sinus bradycardia (40 beats per minute). Initial laboratory test results, including a complete blood count, basic metabolic profile and cardiac biomarkers, were normal. She was admitted for observation on telemetry monitoring. Her heart rate gradually increased and her symptoms resolved. Her outpatient dose of atenolol, taken for symptomatic inappropriate sinus tachycardia, was resumed. Our patient's acute symptoms were attributed to symptomatic sinus bradycardia due to pulse dose steroid treatment. Although several theories have been suggested to explain this phenomenon, the exact mechanism still remains unknown. It does not warrant any specific treatment, as it is a self-limiting side effect that resolves after discontinuing steroid infusion. Young patients who are free of any active cardiac conditions can safely be administered pulse dose steroids without monitoring. However, older patients with active cardiac conditions should have heart rate and blood pressure monitoring during infusion. Our patient also suffered from inappropriate sinus tachycardia, a manifestation of autonomic involvement of multiple sclerosis that has not been previously described. This case has implications for the pathogenesis and treatment of dysautonomia in patients with multiple sclerosis.

Advancing drug delivery systems for the treatment of multiple sclerosis.

PubMed

Tabansky, Inna; Messina, Mark D; Bangeranye, Catherine; Goldstein, Jeffrey; Blitz-Shabbir, Karen M; Machado, Suly; Jeganathan, Venkatesh; Wright, Paul; Najjar, Souhel; Cao, Yonghao; Sands, Warren; Keskin, Derin B; Stern, Joel N H

2015-12-01

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. It is characterized by demyelination of neurons and loss of neuronal axons and oligodendrocytes. In MS, auto-reactive T cells and B cells cross the blood-brain barrier (BBB), causing perivenous demyelinating lesions that form multiple discrete inflammatory demyelinated plaques located primarily in the white matter. In chronic MS, cortical demyelination and progressive axonal transections develop. Treatment for MS can be stratified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs aim to decrease circulating immune cells or to prevent these cells from crossing the BBB and reduce the inflammatory response. There are currently 10 DMTs approved for the relapsing forms of MS; these vary with regard to their efficacy, route and frequency of administration, adverse effects, and toxicity profile. Better drug delivery systems are being developed in order to decrease adverse effects, increase drug efficacy, and increase patient compliance through the direct targeting of pathologic cells. Here, we address the uses and benefits of advanced drug delivery systems, including nanoparticles, microparticles, fusion antibodies, and liposomal formulations. By altering the properties of therapeutic particles and enhancing targeting, breakthrough drug delivery technologies potentially applicable to multiple disease treatments may rapidly emerge.

Environmental Risk Factors for Multiple Sclerosis: A Review with a Focus on Molecular Mechanisms

PubMed Central

O’Gorman, Cullen; Lucas, Robyn; Taylor, Bruce

2012-01-01

Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system commonly affecting young adults. Pathologically, there are patches of inflammation (plaques) with demyelination of axons and oligodendrocyte loss. There is a global latitude gradient in MS prevalence, and incidence of MS is increasing (particularly in females). These changes suggest a major role for environmental factors in causation of disease. We have reviewed the evidence and potential mechanisms of action for three exposures: vitamin D, Epstein Barr virus and cigarette smoking. Recent advances supporting gene-environment interactions are reviewed. Further research is needed to establish mechanisms of causality in humans and to explore preventative strategies. PMID:23109880

Single nucleotide polymorphisms in multiple sclerosis: disease susceptibility and treatment response biomarkers.

PubMed

Pravica, Vera; Popadic, Dusan; Savic, Emina; Markovic, Milos; Drulovic, Jelena; Mostarica-Stojkovic, Marija

2012-04-01

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system characterized by unpredictable and variable clinical course. Etiology of MS involves both genetic and environmental factors. New technologies identified genetic polymorphisms associated with MS susceptibility among which immunologically relevant genes are significantly overrepresented. Although individual genes contribute only a small part to MS susceptibility, they might be used as biomarkers, thus helping to identify accurate diagnosis, predict clinical disease course and response to therapy. This review focuses on recent progress in research on MS genetics with special emphasis on the possibility to use single nucleotide polymorphism of candidate genes as biomarkers of susceptibility to disease and response to therapy.

Mind-Body Medicine for Multiple Sclerosis: A Systematic Review

PubMed Central

Senders, Angela; Wahbeh, Helané; Spain, Rebecca; Shinto, Lynne

2012-01-01

Background. Mind-body therapies are used to manage physical and psychological symptoms in many chronic health conditions. Objective. To assess the published evidence for using mind-body techniques for symptom management of multiple sclerosis. Methods. MEDLINE, PsycINFO, and Cochrane Clinical Trials Register were searched from inception to March 24, 2012. Eleven mind-body studies were reviewed (meditation, yoga, biofeedback, hypnosis, relaxation, and imagery). Results. Four high quality trials (yoga, mindfulness, relaxation, and biofeedback) were found helpful for a variety of MS symptoms. Conclusions. The evidence for mind-body medicine in MS is limited, yet mind-body therapies are relatively safe and may provide a nonpharmacological benefit for MS symptoms. PMID:23227313

Early-Onset Multiple Sclerosis in Isfahan, Iran: Report of the Demographic and Clinical Features of 221 Patients.

PubMed

Etemadifar, Masoud; Nourian, Sayed-Mohammadamin; Nourian, Niloofaralsadat; Abtahi, Seyed-Hossein; Sayahi, Farnaz; Saraf, Zahra; Fereidan-Esfahani, Mahboobeh

2016-06-01

It is estimated that early-onset multiple sclerosis multiple sclerosis (early-onset multiple sclerosis) approximately incorporates 3-5% of the multiple sclerosis population. In this report on early-onset multiple sclerosis, the authors aimed to define demographic, clinical and imaging features in a case-series of true-childhood multiple sclerosis and to compare its characteristics with juvenile multiple sclerosis. The authors inspected the records of multiple sclerosis patients who were registered by Isfahan MS Society. Clinical and demographic data of children with less than 16 years of age were reviewed retrospectively. Out of 4536 multiple sclerosis patients referred to the authors' center, 221 patients (4.8%) had multiple sclerosis starting at the age of 16 or less (11 true-childhood multiple sclerosis vs 210 juvenile-onset multiple sclerosis); the female to male ratio was 4.81:1. In the mean follow-up period of 6.2 years, 22 patients (10.5%) had positive family history of multiple sclerosis, 196 (88.6%) patients were classified as relapsing-remitting multiple sclerosis, the mean (± SD Expanded Disability Status Scale) was 1.5 ± 1.1 at the last evaluation. The most common initial presentation was optic nerve involvement (36.1%) and cerebellar sign and symptoms (14.6%). In all, 13 patients (5.8%) had experienced seizure in the course of multiple sclerosis. This study indicated that early-onset multiple sclerosis is not rare condition and overwhelmingly affects girls even at prepubertal onset. Physicians should consider multiple sclerosis in suspicious pediatric cases. © The Author(s) 2016.

Proton MR spectroscopy of lesion evolution in multiple sclerosis: Steady-state metabolism and its relationship to conventional imaging.

PubMed

Kirov, Ivan I; Liu, Shu; Tal, Assaf; Wu, William E; Davitz, Matthew S; Babb, James S; Rusinek, Henry; Herbert, Joseph; Gonen, Oded

2017-08-01

Although MRI assessment of white matter lesions is essential for the clinical management of multiple sclerosis, the processes leading to the formation of lesions and underlying their subsequent MRI appearance are incompletely understood. We used proton MR spectroscopy to study the evolution of N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (mI) in pre-lesional tissue, persistent and transient new lesions, as well as in chronic lesions, and related the results to quantitative MRI measures of T1-hypointensity and T2-volume. Within 10 patients with relapsing-remitting course, there were 180 regions-of-interest consisting of up to seven semi-annual follow-ups of normal-appearing white matter (NAWM, n = 10), pre-lesional tissue giving rise to acute lesions which resolved (n = 3) or persisted (n = 3), and of moderately (n = 9) and severely hypointense (n = 6) chronic lesions. Compared with NAWM, pre-lesional tissue had higher Cr and Cho, while compared with lesions, pre-lesional tissue had higher NAA. Resolving acute lesions showed similar NAA levels pre- and post-formation, suggesting no long-term axonal damage. In chronic lesions, there was an increase in mI, suggesting accumulating astrogliosis. Lesion volume was a better predictor of axonal health than T1-hypointensity, with lesions larger than 1.5 cm 3 uniformly exhibiting very low (<4.5 millimolar) NAA concentrations. A positive correlation between longitudinal changes in Cho and in lesion volume in moderately hypointense lesions implied that lesion size is mediated by chronic inflammation. These and other results are integrated in a discussion on the steady-state metabolism of lesion evolution in multiple sclerosis, viewed in the context of conventional MRI measures. Hum Brain Mapp 38:4047-4063, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Can the Fatigue Severity Scale 7-item version be used across different patient populations as a generic fatigue measure - a comparative study using a Rasch model approach

PubMed Central

2014-01-01

Background Fatigue is a disabling symptom associated with reduced quality of life in various populations living with chronic illnesses. The transfer of knowledge about fatigue from one group to another is crucial in both research and healthcare. Outcomes should be validly and reliably comparable between groups and should not be unduly influenced by diagnostic variations. The present study evaluates whether the Fatigue Severity Scale 7-item version (FSS-7) demonstrates similar item hierarchy across people with multiple sclerosis, stroke or HIV/AIDS to ensure valid comparisons between groups, and provide further evidence of internal scale validity. Methods A secondary comparative analysis was performed using data from three different studies of three different chronic illnesses: multiple sclerosis, stroke and HIV/AIDS. Each of these studies had previously concluded that the FSS-7 has better psychometric properties than the original FSS for measuring fatigue interference. Data from 224 people with multiple sclerosis, 104 people with stroke and 316 people with HIV/AIDS were examined. Item response theory and a Rasch model were chosen to analyze the similarity of the FSS-7 item hierarchy across the three diagnostic groups Results Cross-sample differences were found for items #3, #5, #6 and #9 for two of the three samples, which raise questions about item validity across groups. However, disease-specific and disease-generic Rasch measures were similar across samples, indicating that individual fatigue interference measures in these three chronic illnesses might still be reliably comparable using the FSS-7. Conclusions Some items performed differently between the three samples but did not bias person measures, thereby indicating that fatigue interference in these illnesses might still be reliably compared using FSS-7 scores. However, caution is warranted when comparing fatigue raw sum scores directly across diagnostic groups using the FSS-7. Further studies of the scale are needed in other types of chronic illnesses. PMID:24559076

Comparing face-to-face and online qualitative research with people with multiple sclerosis.

PubMed

Synnot, Anneliese; Hill, Sophie; Summers, Michael; Taylor, Michael

2014-03-01

We compared face-to-face focus groups and an online forum in qualitative research with people with multiple sclerosis (MS) and family members. Although the merits and challenges of online qualitative research have been considered by others, there is limited literature directly comparing these two data collection methods for people with disability or chronic illness. Twenty-seven people participated in one of four focus groups and 33 people took part in an online forum. Demographic and MS-related characteristics were similar between the two groups, with a slight nonsignificant trend toward nonmetropolitan residence in online forum participants. There was a high level of overlap in the themes generated between groups. Participant responses in the online forum were more succinct and on-topic, yet in the focus groups interaction was greater. Online qualitative research methods can facilitate research participation for people with chronic illness or disability, yielding generally comparable information to that gathered via face-to-face methods.

Failure to detect genomic material of HTLV-I or HTLV-II in mononuclear cells of Italian patients with multiple sclerosis and chronic progressive myelopathy.

PubMed

Merelli, E; Sola, P; Marasca, R; Salati, R; Torelli, G

1993-01-01

To contribute to the undecided question if a retrovirus of the human T-cell lymphotropic virus (HTLV) family may be involved in the development of multiple sclerosis (MS), we investigated by the polymerase chain reaction (PCR) the presence of HTLV-I and HTLV-II sequences in the peripheral blood mononuclear cell DNAs from 30 patients affected by MS and 15 by chronic progressive myelopathy. Moreover a control group of 14 blood donors was examined. All these patients were devoid of anti-HTLV-I antibody in the serum and cerebrospinal fluid at ELISA. For the PCR, primers and probes specific for the tax region common to HTLV-I and HTLV-II, for the pol region of HTLV-I, and for the pol region of HTLV-II were used. In spite of the high sensitivity of the technique used, the three groups of subjects were negative for HTLV-I and HTLV-II genomic sequences.

Self-Management for People with Multiple Sclerosis

PubMed Central

Fraser, Robert; Ehde, Dawn; Amtmann, Dagmar; Johnson, Kurt L.; Johnson, Erica; Kraft, George H.

2013-01-01

People with multiple sclerosis (MS) must manage the day-to-day effects of the disease on their lives. Self-management interventions may be helpful in this challenge. An international, multidisciplinary consensus conference was held on November 15, 2010, by the University of Washington's Rehabilitation Research and Training Center for Multiple Sclerosis (MS RRTC), with funding from the Consortium of Multiple Sclerosis Centers (CMSC) and the National Institute on Disability and Rehabilitation Research (NIDRR), to discuss the concept of self-management for people with MS. The specific goals of the consensus conference were as follows: 1) review the current research on self-management and related issues in chronic disability and specifically in MS; 2) review optimal research methodologies, outcome measurement tools, program planning frameworks, and dissemination strategies for self-management research; and 3) establish recommendations on the next steps necessary to develop, adapt, and test self-management interventions for people with MS. The consensus conference and this document are the initial steps toward achieving the stated goals. Participants in the consensus conference concluded that it is necessary to: 1) define an empirically based conceptual model of self-management for people with MS; 2) establish reliable and valid self-management outcome measures; 3) use best practices to validate models of self-management interventions; and 4) plan dissemination and knowledge translation of interventions once their effectiveness is established. PMID:24453769

The topograpy of demyelination and neurodegeneration in the multiple sclerosis brain.

PubMed

Haider, Lukas; Zrzavy, Tobias; Hametner, Simon; Höftberger, Romana; Bagnato, Francesca; Grabner, Günther; Trattnig, Siegfried; Pfeifenbring, Sabine; Brück, Wolfgang; Lassmann, Hans

2016-03-01

Multiple sclerosis is a chronic inflammatory disease with primary demyelination and neurodegeneration in the central nervous system. In our study we analysed demyelination and neurodegeneration in a large series of multiple sclerosis brains and provide a map that displays the frequency of different brain areas to be affected by these processes. Demyelination in the cerebral cortex was related to inflammatory infiltrates in the meninges, which was pronounced in invaginations of the brain surface (sulci) and possibly promoted by low flow of the cerebrospinal fluid in these areas. Focal demyelinated lesions in the white matter occurred at sites with high venous density and additionally accumulated in watershed areas of low arterial blood supply. Two different patterns of neurodegeneration in the cortex were identified: oxidative injury of cortical neurons and retrograde neurodegeneration due to axonal injury in the white matter. While oxidative injury was related to the inflammatory process in the meninges and pronounced in actively demyelinating cortical lesions, retrograde degeneration was mainly related to demyelinated lesions and axonal loss in the white matter. Our data show that accumulation of lesions and neurodegeneration in the multiple sclerosis brain does not affect all brain regions equally and provides the pathological basis for the selection of brain areas for monitoring regional injury and atrophy development in future magnetic resonance imaging studies. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Effects of Multidisciplinary Rehabilitation on Chronic Fatigue in Multiple Sclerosis: A Randomized Controlled Trial

PubMed Central

Rietberg, Marc B.; van Wegen, Erwin E. H.; Eyssen, Isaline C. J. M.; Kwakkel, Gert

2014-01-01

Background Several rehabilitation programmes aim at reducing the impact of fatigue in MS patients. Acute and chronic fatigue should require different management. Objectives To assess the effects of individually tailored, multidisciplinary outpatient rehabilitation (MDR) on chronic fatigue. Methods Forty-eight ambulatory MS patients with chronic fatigue were randomized to MDR or to MS–nurse consultation. Fatigue was assessed by the Checklist Individual Strength (CIS-20R). Secondary outcomes included the Modified Fatigue Impact Scale, Fatigue Severity Scale, Functional Independence Measure, Disability and Impact Profile (DIP), Multiple Sclerosis Impact Scale and the Impact on Participation and Autonomy (IPA). Results The primary outcome measure CIS-20R overall score showed no significant differences between groups at 12 weeks (P = 0.39) and 24 weeks follow-up (P = 0.14), nor for subscales (t = 12 and t = 24, 0.19≤P≤0.88). No significant within-group effects were found for both groups with respect to the primary (0.57≤p≤0.97) and secondary (0.11≤p≤0.92) outcome measures from baseline to 12 or 24 weeks. Conclusion Multidisciplinary rehabilitation was not more effective in terms of reducing self-reported fatigue in MS patients compared to MS-nurse consultation. Our results suggest that chronic fatigue in patients with MS may be highly invariant over time, irrespective of interventions. Trial Registration controlled-trials.com ISRCTN05017507 PMID:25232955

Increased mitochondrial content in remyelinated axons: implications for multiple sclerosis

PubMed Central

Zambonin, Jessica L.; Zhao, Chao; Ohno, Nobuhiko; Campbell, Graham R.; Engeham, Sarah; Ziabreva, Iryna; Schwarz, Nadine; Lee, Sok Ee; Frischer, Josa M.; Turnbull, Doug M.; Trapp, Bruce D.; Lassmann, Hans; Franklin, Robin J. M.

2011-01-01

Mitochondrial content within axons increases following demyelination in the central nervous system, presumably as a response to the changes in energy needs of axons imposed by redistribution of sodium channels. Myelin sheaths can be restored in demyelinated axons and remyelination in some multiple sclerosis lesions is extensive, while in others it is incomplete or absent. The effects of remyelination on axonal mitochondrial content in multiple sclerosis, particularly whether remyelination completely reverses the mitochondrial changes that follow demyelination, are currently unknown. In this study, we analysed axonal mitochondria within demyelinated, remyelinated and myelinated axons in post-mortem tissue from patients with multiple sclerosis and controls, as well as in experimental models of demyelination and remyelination, in vivo and in vitro. Immunofluorescent labelling of mitochondria (porin, a voltage-dependent anion channel expressed on all mitochondria) and axons (neurofilament), and ultrastructural imaging showed that in both multiple sclerosis and experimental demyelination, mitochondrial content within remyelinated axons was significantly less than in acutely and chronically demyelinated axons but more numerous than in myelinated axons. The greater mitochondrial content within remyelinated, compared with myelinated, axons was due to an increase in density of porin elements whereas increase in size accounted for the change observed in demyelinated axons. The increase in mitochondrial content in remyelinated axons was associated with an increase in mitochondrial respiratory chain complex IV activity. In vitro studies showed a significant increase in the number of stationary mitochondria in remyelinated compared with myelinated and demyelinated axons. The number of mobile mitochondria in remyelinated axons did not significantly differ from myelinated axons, although significantly greater than in demyelinated axons. Our neuropathological data and findings in experimental demyelination and remyelination in vivo and in vitro are consistent with a partial amelioration of the supposed increase in energy demand of demyelinated axons by remyelination. PMID:21705418

Effect of aerobic interval training on serum IL-10, TNFα, and adipokines levels in women with multiple sclerosis: possible relations with fatigue and quality of life.

PubMed

Mokhtarzade, Motahare; Ranjbar, Rouholah; Majdinasab, Nastaran; Patel, Darpan; Molanouri Shamsi, Mehdieh

2017-08-01

Multiple sclerosis is associated with immune system dysfunction and chronic inflammation; however, possible relations between immunologic and metabolic factors and some psychological indexes such as fatigue and quality of life, especially in relation to exercise training, have not yet been investigated. The present study was designed to investigate the effect of aerobic interval training on interleukin-10/tumor necrosis factor ratio and adipokine (leptin and adiponectin) concentrations in women with multiple sclerosis. Furthermore, the relationship between these factors with fatigue and quality of life were assessed. Forty women with multiple sclerosis (Expanded Disability Status Scale ≤3) were randomized into either a non-exercising control or training group. The training group performed 8-weeks of upper and lower limb aerobic interval training. Serum concentrations of tumor necrosis factorα, interleukin-10, leptin, and adiponectin were measured before and after the 8-week intervention. Moreover, antropometric measures and measures for fatigue and quality of life were determined at the onset of and after exercise training. The results revealed that leptin and tumor necrosis factorα levels significantly decreased subsequent to the aerobic interval training. Although blood adiponectin levels considerably increased in the training group, interleukin-10 and interleukin-10/tumor necrosis factorα ratio underwent no substantial change after the exercise training. In addition, the aerobic interval training was associated with improvement in fatigue, quality of life, and maximal oxygen consumption. Our findings suggested that aerobic interval training can be an effective strategy for managing the immune system at least by its significant impact on inflammatory cytokines and adipokines levels in women with multiple sclerosis. Additionally, this positive impact improved fatigue and adipose tissue indicators.

Increased mitochondrial content in remyelinated axons: implications for multiple sclerosis.

PubMed

Zambonin, Jessica L; Zhao, Chao; Ohno, Nobuhiko; Campbell, Graham R; Engeham, Sarah; Ziabreva, Iryna; Schwarz, Nadine; Lee, Sok Ee; Frischer, Josa M; Turnbull, Doug M; Trapp, Bruce D; Lassmann, Hans; Franklin, Robin J M; Mahad, Don J

2011-07-01

Mitochondrial content within axons increases following demyelination in the central nervous system, presumably as a response to the changes in energy needs of axons imposed by redistribution of sodium channels. Myelin sheaths can be restored in demyelinated axons and remyelination in some multiple sclerosis lesions is extensive, while in others it is incomplete or absent. The effects of remyelination on axonal mitochondrial content in multiple sclerosis, particularly whether remyelination completely reverses the mitochondrial changes that follow demyelination, are currently unknown. In this study, we analysed axonal mitochondria within demyelinated, remyelinated and myelinated axons in post-mortem tissue from patients with multiple sclerosis and controls, as well as in experimental models of demyelination and remyelination, in vivo and in vitro. Immunofluorescent labelling of mitochondria (porin, a voltage-dependent anion channel expressed on all mitochondria) and axons (neurofilament), and ultrastructural imaging showed that in both multiple sclerosis and experimental demyelination, mitochondrial content within remyelinated axons was significantly less than in acutely and chronically demyelinated axons but more numerous than in myelinated axons. The greater mitochondrial content within remyelinated, compared with myelinated, axons was due to an increase in density of porin elements whereas increase in size accounted for the change observed in demyelinated axons. The increase in mitochondrial content in remyelinated axons was associated with an increase in mitochondrial respiratory chain complex IV activity. In vitro studies showed a significant increase in the number of stationary mitochondria in remyelinated compared with myelinated and demyelinated axons. The number of mobile mitochondria in remyelinated axons did not significantly differ from myelinated axons, although significantly greater than in demyelinated axons. Our neuropathological data and findings in experimental demyelination and remyelination in vivo and in vitro are consistent with a partial amelioration of the supposed increase in energy demand of demyelinated axons by remyelination.

Supporting work for people with multiple sclerosis.

PubMed

Doogan, Catherine; Playford, E Diane

2014-05-01

People with multiple sclerosis experience some of the highest rates of unemployment among groups of individuals with severe and chronic disabilities. While unpredictable relapses, physical and cognitive symptoms all may play a role in job loss, it is more likely that job loss can be attributed to a complex interaction between disease-related factors and contextual factors, such as the working environment, and employer attitudes. This interaction leads to the concept of work instability, that is, the mismatch between work demands and the individual's capacity to meet these demands. Vocational rehabilitation services aim to provide people with multiple sclerosis vocational assessment, rehabilitation and support to enable them to find, regain or remain in work and access other occupational and educational opportunities. Such services consist of a multidisciplinary team with the ability to provide education around disclosure, and work-place accommodations, offer emotional support, maintain work performance, liaise with employers, and support to re-enter the workplace. Helpful interventions include early disclosure, proper workplace accommodation, education of employers, and government-funded initiatives to support disabled employees. Future research needs to agree on methods of recording outcomes and evaluate specific vocational rehabilitation interventions.

Music therapy in the treatment of multiple sclerosis: a comprehensive literature review.

PubMed

Ostermann, Thomas; Schmid, Wolfgang

2006-04-01

Coping with multiple sclerosis symptoms still remains a challenge for each patient suffering from this chronic inflammatory disease. Therefore, patients often turn to using complementary and alternative medicine (CAM). In this review, the authors aimed to investigate the current state of literature of music therapy in the treatment of multiple sclerosis (MS). Medline, PubMed, Embase, AMED, CAMbase and the Music Therapy World Journal Index were searched for the terms MS and 'music therapy'. In addition, an internet search using Google Scholar was performed. The authors found seven case-reports/series and seven studies on music therapy for MS-patients. Both the case reports and studies presented here are pioneer work. Most of the studies are naturally predominated by the use of qualitative and uncontrolled research designs. Nevertheless, the results of the studies as well as the case reports demonstrate patients' improvement in the domains of self-acceptance, anxiety and depression. The results of the studies as well as the case reports define a sufficient basis for further music therapeutical work as they show a variety of psychosocial and emotional benefits for MS patients.

The Efficacy of Functional Electrical Stimulation of the Abdominal Muscles in the Treatment of Chronic Constipation in Patients with Multiple Sclerosis: A Pilot Study

PubMed Central

Peace, Carla

2016-01-01

Chronic constipation in patients with multiple sclerosis (MS) is common and the current methods of treatment are ineffective in some patients. Anecdotal observations suggest that functional electrical stimulation (FES) of the abdominal muscles may be effective in the management of constipation in these patients. Patients and Methods. In this exploratory investigation we studied the effects of FES on the whole gut transit time (WGTT) and the colonic transit time (CTT). In addition, we evaluated the treatment effect on the patients' constipation-related quality of life and on the use of laxatives and the use of manual bowel evacuation. FES was given for 30 minutes twice a day for a period of six weeks. Four female patients were studied. Results. The WGTT and CTT and constipation-related quality of life improved in all patients. The patients' use of laxatives was reduced. No adverse effects of FES treatment were reported. Conclusion. The findings of this pilot study suggest that FES applied to the abdominal muscles may be an effective treatment modality for severe chronic constipation in patients with MS. PMID:27200190

Viruses and Multiple Sclerosis

PubMed Central

Owens, Gregory P.; Gilden, Don; Burgoon, Mark P.; Yu, Xiaoli; Bennett, Jeffrey L.

2012-01-01

Multiple sclerosis (MS) is a chronic demyelinating disorder of unknown etiology, possibly caused by a virus or virus-triggered immunopathology. The virus might reactivate after years of latency and lyse oligodendrocytes, as in progressive multifocal leukoencephalopathy, or initiate immunopathological demyelination, as in animals infected with Theiler’s murine encephalomyelitis virus or coronaviruses. The argument for a viral cause of MS is supported by epidemiological analyses and studies of MS in identical twins, indicating that disease is acquired. However, the most important evidence is the presence of bands of oligoclonal IgG (OCBs) in MS brain and CSF that persist throughout the lifetime of the patient. OCBs are found almost exclusively in infectious CNS disorders, and antigenic targets of OCBs represent the agent that causes disease. Here, the authors review past attempts to identify an infectious agent in MS brain cells and discuss the promise of using recombinant antibodies generated from clonally expanded plasma cells in brain and CSF to identify disease-relevant antigens. They show how this strategy has been used successfully to analyze antigen specificity in subacute sclerosing panencephalitis, a chronic encephalitis caused by measles virus, and in neuromyelitis optica, a chronic autoimmune demyelinating disease produced by antibodies directed against the aquaporin-4 water channel. PMID:22130640

Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota

PubMed Central

van den Hoogen, Ward J.; Laman, Jon D.; ’t Hart, Bert A.

2017-01-01

Multiple sclerosis (MS) is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS), leading to demyelination, axonal damage, and symptoms such as fatigue and disability. Although the cause of MS is not known, the infiltration of peripherally activated immune cells into the CNS has a key pathogenic role. Accumulating evidence supports an important role of diet and gut microbiota in immune-mediated diseases. Preclinical as well as clinical studies suggest a role for gut microbiota and dietary components in MS. Here, we review these recent studies on gut microbiota and dietary interventions in MS and its animal model experimental autoimmune encephalomyelitis. We also propose directions for future research. PMID:28928747

Characterisation of tissue-type metabolic content in secondary progressive multiple sclerosis: a magnetic resonance spectroscopic imaging study.

PubMed

Marshall, Ian; Thrippleton, Michael J; Bastin, Mark E; Mollison, Daisy; Dickie, David A; Chappell, Francesca M; Semple, Scott I K; Cooper, Annette; Pavitt, Sue; Giovannoni, Gavin; Wheeler-Kingshott, Claudia A M Gandini; Solanky, Bhavana S; Weir, Christopher J; Stallard, Nigel; Hawkins, Clive; Sharrack, Basil; Chataway, Jeremy; Connick, Peter; Chandran, Siddharthan

2018-05-30

Proton magnetic resonance spectroscopy yields metabolic information and has proved to be a useful addition to structural imaging in neurological diseases. We applied short-echo time Spectroscopic Imaging in a cohort of 42 patients with secondary progressive multiple sclerosis (SPMS). Linear modelling with respect to brain tissue type yielded metabolite levels that were significantly different in white matter lesions compared with normal-appearing white matter, suggestive of higher myelin turnover (higher choline), higher metabolic rate (higher creatine) and increased glial activity (higher myo-inositol) within the lesions. These findings suggest that the lesions have ongoing cellular activity that is not consistent with the usual assumption of 'chronic' lesions in SPMS, and may represent a target for repair therapies.

Generation of six multiple sclerosis patient-derived induced pluripotent stem cell lines.

PubMed

Miquel-Serra, L; Duarri, A; Muñoz, Y; Kuebler, B; Aran, B; Costa, C; Martí, M; Comabella, M; Malhotra, S; Montalban, X; Veiga, A; Raya, A

2017-10-01

Multiple sclerosis (MS) is considered a chronic autoimmune disease of the central nervous system that leads to gliosis, demyelination, axonal damage and neuronal death. The MS disease aetiology is unknown, though a polymorphism of the TNFRSF1A gene, rs1800693, is known to confer an increased risk for MS. Using retroviral delivery of reprogramming transgenes, we generated six MS patient-specific iPSC lines with two distinct genotypes, CC or TT, of the polymorphism rs1800693. iPSC lines had normal karyotype, expressed pluripotency genes and differentiated into the three germ layers. These lines offer a good tool to study MS pathomechanisms and for drug testing. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Emerging Role for Methylation in Multiple Sclerosis: Beyond DNA.

PubMed

Webb, Lindsay M; Guerau-de-Arellano, Mireia

2017-06-01

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The inflammatory and neurodegenerative pathways driving MS are modulated by DNA, lysine, and arginine methylation, as evidenced by studies made possible by novel tools for methylation detection or loss of function. We present evidence that MS is associated with genetic variants and metabolic changes that impact on methylation. Further, we comprehensively review current understanding of how methylation can impact on central nervous system (CNS) resilience and neuroregenerative potential, as well as inflammatory versus regulatory T helper (Th) cell balance. These findings are discussed in the context of therapeutic relevance for MS, with broad implications in other neurologic and immune-mediated diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

[The influence of high-tone power therapy on the functional status of patients with multiple sclerosis].

PubMed

Kubsik, Anna; Klimkiewicz, Paulina; Klimkiewicz, Robert; Jankowska, Katarzyna; Jankowska, Agnieszka; Woldańska-Okońska, Marta

2014-07-01

Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system, which is characterized by diverse symptomatology. Most often affects people at a young age gradually leading to their disability. Looking for new therapies to alleviate neurological deficits caused by the disease. One of the alternative methods of therapy is high - tone power therapy. The article is a comparison of high-tone power therapy and kinesis in improving patients with multiple sclerosis. The aim of this study was to evaluate the effectiveness of high-tone power therapy and exercises in kinesis on the functional status of patients with multiple sclerosis. The study involved 20 patients with multiple sclerosis, both sexes, treated at the Department of Rehabilitation and Physical Medicine in Lodz. Patients were randomly divided into two groups studied. In group high-tone power therapy applied for 60 minutes, while in group II were used exercises for kinesis. Treatment time for both groups of patients was 15 days. To assess the functional status scale was used: Expanded Disability Status Scale of Kurtzke (EDSS), as well as by Barthel ADL Index. Assessment of quality of life were made using MSQOL Questionnaire-54. For the evaluation of gait and balance using Tinetti scale, and pain VAS rated, and Laitinen. Changes in muscle tone was assessed on the basis of the Ashworth scale. Both group I and II improved on scales conducted before and after therapy. In group I, in which the applied high-tone power therapy, reported statistically significant results in 9 out of 10 tested parameters, while in group II, which was used in the exercises in kinesis an improvement in 6 out of 10 tested parameters. Correlating the results of both the test groups in relation to each other did not show statistically significant differences. High-Tone Power Therapy beneficial effect on the functional status of patients with multiple sclerosis. Obtaining results in terms of number of tested parameters allows for the use of this therapy in the comprehensive improvement of patients with multiple sclerosis. Exercises from the scheme kinesis favorable impact on the functional status of patients with MS and are essential in the rehabilitation of these patients. In any group, no adverse effects were observed.

Clinical Characteristics of Pediatric-Onset and Adult-Onset Multiple Sclerosis in Hispanic Americans.

PubMed

Langille, Megan M; Islam, Talat; Burnett, Margaret; Amezcua, Lilyana

2016-07-01

Multiple sclerosis can affect pediatric patients. Our aim was to compare characteristics between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanic Americans. This was a cross-sectional analysis of 363 Hispanic American multiple scleroses cases; demographic and clinical characteristics were analyzed. A total of 110 Hispanic patients presented with multiple sclerosis before age 18 and 253 as adult multiple sclerosis. The most common presenting symptoms for both was optic neuritis. Polyfocal symptoms, seizures, and cognitive symptoms at presentation were more prevalent in pediatric-onset multiple sclerosis (P ≤ .001). Transverse myelitis was more frequent in adult-onset multiple sclerosis (P ≤ .001). Using multivariable analysis, pediatric-onset multiple sclerosis (adjusted odds ratio, 0.3OR 95% confidence interval 0.16-0.71, P = .004) and being US born (adjusted odds ratio, 0.553, 95% confidence interval 0.3-1.03, P = .006) were less likely to have severe ambulatory disability. Results suggest that pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanics have differences that could be important for treatment and prognosis. © The Author(s) 2016.

Cannabis use in palliative care - an examination of the evidence and the implications for nurses.

PubMed

Green, Anita J; De-Vries, Kay

2010-09-01

Examine the pharmaceutical qualities of cannabis including a historical overview of cannabis use. Discuss the use of cannabis as a clinical intervention for people experiencing palliative care, including those with life-threatening chronic illness such as multiple sclerosis and motor neurone disease [amyotrophic lateral sclerosis] in the UK. The non-medicinal use of cannabis has been well documented in the media. There is a growing scientific literature on the benefits of cannabis in symptom management in cancer care. Service users, nurses and carers need to be aware of the implications for care and treatment if cannabis is being used medicinally. A comprehensive literature review. Literature searches were made of databases from 1996 using the term cannabis and the combination terms of cannabis and palliative care; symptom management; cancer; oncology; chronic illness; motor neurone disease/amyotrophic lateral sclerosis; and multiple sclerosis. Internet material provided for service users searching for information about the medicinal use of cannabis was also examined. The literature on the use of cannabis in health care repeatedly refers to changes for users that may be equated with improvement in quality of life as an outcome of its use. This has led to increased use of cannabis by these service users. However, the cannabis used is usually obtained illegally and can have consequences for those who choose to use it for its therapeutic value and for nurses who are providing care. Questions and dilemmas are raised concerning the role of the nurse when caring and supporting a person making therapeutic use of cannabis. © 2010 Blackwell Publishing Ltd.

Limb myokymia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albers, J.W.; Allen, A.A.; Bastron, J.A.

Thirty-eight patients with myokymic discharges localized to limb muscles on needle electromyography had various neurologic lesions, both acute and chronic. Of the 38 patients, 27 had had previous radiation therapy and the clinical diagnosis of radiation-induced plexopathy, myelopathy, or both. For the remaining 11 patients, the diagnoses included multiple sclerosis, inflammatory polyradiculoneuropathy, ischemic neuropathy, inflammatory myopathy, and chronic disorders of the spinal cord and peripheral nerves. The clinical presentations and results of local ischemia, peripheral nerve block, and percutaneous stimulation suggest that most limb myokymic discharges arise focally at the site of a chronic peripheral nerve lesion.

Iron Is a Sensitive Biomarker for Inflammation in Multiple Sclerosis Lesions

PubMed Central

Mehta, Veela; Pei, Wei; Yang, Grant; Li, Suyang; Swamy, Eashwar; Boster, Aaron; Schmalbrock, Petra; Pitt, David

2013-01-01

MRI phase imaging in multiple sclerosis (MS) patients and in autopsy tissue have demonstrated the presence of iron depositions in white matter lesions. The accumulation of iron in some but not all lesions suggests a specific, potentially disease-relevant process, however; its pathophysiological significance remains unknown. Here, we explore the role of lesional iron in multiple sclerosis using multiple approaches: immunohistochemical examination of autoptic MS tissue, an in vitro model of iron-uptake in human cultured macrophages and ultra-highfield phase imaging of highly active and of secondary progressive MS patients. Using Perls' stain and immunohistochemistry, iron was detected in MS tissue sections predominantly in non-phagocytosing macrophages/microglia at the edge of established, demyelinated lesions. Moreover, iron-containing macrophages but not myelin-laden macrophages expressed markers of proinflammatory (M1) polarization. Similarly, in human macrophage cultures, iron was preferentially taken up by non-phagocytosing, M1-polarized macrophages and induced M1 (super) polarization. Iron uptake was minimal in myelin-laden macrophages and active myelin phagocytosis led to depletion of intracellular iron. Finally, we demonstrated in MS patients using GRE phase imaging with ultra-highfield MRI that phase hypointense lesions were significantly more prevalent in patients with active relapsing than with secondary progressive MS. Taken together, our data provide a basis to interpret iron-sensitive GRE phase imaging in MS patients: iron is present in non-phagocytosing, M1-polarized microglia/macrophages at the rim of chronic active white matter demyelinating lesions. Phase imaging may therefore visualize specific, chronic proinflammatory activity in established MS lesions and thus provide important clinical information on disease status and treatment efficacy in MS patients. PMID:23516409

Featured Article: Serum [Met5]-enkephalin levels are reduced in multiple sclerosis and restored by low-dose naltrexone.

PubMed

Ludwig, Michael D; Zagon, Ian S; McLaughlin, Patricia J

2017-09-01

Low-dose naltrexone is a widely used off-label therapeutic prescribed for a variety of immune-related disorders. The mechanism underlying low-dose naltrexone's efficacy for fatigue, Crohn's disease, fibromyalgia, and multiple sclerosis is, in part, intermittent blockade of opioid receptors followed by upregulation of endogenous opioids. Short, intermittent blockade by naltrexone specifically blocks the opioid growth factor receptor resulting in biofeedback events that increase production of the endogenous opioid growth factor (OGF) (chemically termed [Met 5 ]-enkephalin) facilitating interactions between opioid growth factor and opioid growth factor receptor that ultimately, result in inhibited cell proliferation. Preclinical studies have reported that enkephalin levels are deficient in animal models of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. Our hypothesis is that serum enkephalin levels are diminished in humans with multiple sclerosis and experimental autoimmune encephalomyelitis mice, and that change in serum opioid growth factor levels may serve as a reasonable candidate biomarker for the onset of experimental autoimmune encephalomyelitis and response to therapy. To address this, we designed a two-part study to measure endogenous opioids in multiple sclerosis patients, and to investigate the temporal pattern of decline in serum enkephalin concentrations in mice with chronic progressive experimental autoimmune encephalomyelitis and treated with low-dose naltrexone. For comparison, we investigated whether low-dose naltrexone exposure in normal mice also resulted in altered enkephalin levels. In both animal models, we monitored tactile and heat sensitivity, as well as differential white blood cell counts as indicators of inflammation. Serum [Met 5 ]-enkephalin levels were lower in humans with multiple sclerosis relative to non-multiple sclerosis patients, and low-dose naltrexone restored their levels. In experimental autoimmune encephalomyelitis mice, [Met 5 ]-enkephalin levels were depressed prior to the appearance of clinical disease, and were restored with low-dose naltrexone treatment. Low-dose naltrexone therapy had no effect on serum [Met 5 ]-enkephalin or β-endorphin in normal mice. Thus, [Met 5 ]-enkephalin (i.e. opioid growth factor) may be a reasonable candidate biomarker for multiple sclerosis, and may signal new pathways for treatment of autoimmune disorders. Impact statement This report presents human and animal data identifying a novel biomarker for the onset and progression of multiple sclerosis (MS). Humans diagnosed with MS have reduced serum levels of OGF (i.e. [Met 5 ]-enkephalin) relative to non-MS neurologic patients, and low-dose naltrexone (LDN) therapy restored their enkephalin levels. Serum OGF levels were reduced in mice immunized with MOG 35-55 prior to any clinical behavioral sign of experimental autoimmune encephalomyelitis, and LDN therapy restored their serum OGF levels. β-endorphin concentrations were not altered by LDN in humans or mice. Thus, blood levels of OGF may serve as a new, selective biomarker for the progression of MS, as well as response to therapy.

Strategies to reduce hyperthermia in ambulatory multiple sclerosis patients.

PubMed

Edlich, Richard F; Buschbacher, Ralph M; Cox, Mary Jude; Long, William B; Winters, Kathryne L; Becker, Daniel G

2004-01-01

Approximately 400,000 Americans have multiple sclerosis. Worldwide, multiple sclerosis affects 2.5 million individuals. Multiple sclerosis affects two to three times as many women as men. The adverse effects of hyperthermia in patients with multiple sclerosis have been known since 1890. While most patients with multiple sclerosis experience reversible worsening of their neurologic deficits, some patients experience irreversible neurologic deficits. In fact, heat-induced fatalities have been encountered in multiple sclerosis patients subjected to hyperthermia. Hyperthermia can be caused through sun exposure, exercise, and infection. During the last 50 years, numerous strategies have evolved to reduce hyperthermia in individuals with multiple sclerosis, such as photoprotective clothing, sunglasses, sunscreens, hydrotherapy, and prevention of urinary tract infections. Hydrotherapy has become an essential component of rehabilitation for multiple sclerosis patients in hospitals throughout the world. On the basis of this positive hospital experience, hydrotherapy has been expanded through the use of compact aquatic exercise pools at home along with personal cooling devices that promote local and systemic hypothermia in multiple sclerosis patients. The Multiple Sclerosis Association of America and NASA have played leadership roles in developing and recommending technology that will prevent hyperthermia in multiple sclerosis patients and should be consulted for new technological advances that will benefit the multiple sclerosis patient. In addition, products recommended for photoprotection by The Skin Cancer Foundation may also be helpful to the multiple sclerosis patient's defense against hyperthermia. Infections in the urinary tract, especially detrusor-external sphincter dyssynergia, are initially managed conservatively with intermittent self-catheterization and pharmacologic therapy. In those cases, refractory to conservative therapy, transurethral external sphincterotomy followed by condom catheter drainage is recommended. However, if external urethral sphincterotomy fails to reduce residual urine and detrusor pressure, urinary diversion or bladder reconstruction may be necessary.

Flow cytometric analysis reveals the high levels of platelet activation parameters in circulation of multiple sclerosis patients.

PubMed

Morel, Agnieszka; Rywaniak, Joanna; Bijak, Michał; Miller, Elżbieta; Niwald, Marta; Saluk, Joanna

2017-06-01

The epidemiological studies confirm an increased risk of cardiovascular disease in multiple sclerosis, especially prothrombotic events directly associated with abnormal platelet activity. The aim of our study was to investigate the level of blood platelet activation in the circulation of patients with chronic phase of multiple sclerosis (SP MS) and their reactivity in response to typical platelets' physiological agonists. We examined 85 SP MS patients diagnosed according to the revised McDonald's criteria and 50 healthy volunteers as a control group. The platelet activation and reactivity were assessed using flow cytometry analysis of the following: P-selectin expression (CD62P), activation of GP IIb/IIIa complex (PAC-1 binding), and formation of platelet microparticles (PMPs) and platelet aggregates (PA) in agonist-stimulated (ADP, collagen) and unstimulated whole blood samples. Furthermore, we measured the level of soluble P-selectin (sP-selectin) in plasma using ELISA method, to evaluate the in vivo level of platelet activation, both in healthy and SP MS subjects. We found a statistically significant increase in P-selectin expression, GP IIb/IIIa activation, and formation of PMPs and PA, as well as in unstimulated and agonist-stimulated (ADP, collagen) platelets in whole blood samples from patients with SP MS in comparison to the control group. We also determined the higher sP-selectin level in plasma of SP MS subjects than in the control group. Based on the obtained results, we might conclude that during the course of SP MS platelets are chronically activated and display hyperreactivity to physiological agonists, such as ADP or collagen.

USE OF NEUROFEEDBACK AND MINDFULNESS TO ENHANCE RESPONSE TO HYPNOSIS TREATMENT IN INDIVIDUALS WITH MULTIPLE SCLEROSIS: Results From a Pilot Randomized Clinical Trial.

PubMed

Jensen, Mark P; Battalio, Samuel L; Chan, Joy F; Edwards, Karlyn A; Day, Melissa A; Sherlin, Leslie H; Ehde, Dawn M

2018-01-01

This pilot study evaluated the possibility that 2 interventions hypothesized to increase slower brain oscillations (e.g., theta) may enhance the efficacy of hypnosis treatment, given evidence that hypnotic responding is associated with slower brain oscillations. Thirty-two individuals with multiple sclerosis and chronic pain, fatigue, or both, were randomly assigned to 1 of 2 interventions thought to increase slow wave activity (mindfulness meditation or neurofeedback training) or no enhancing intervention, and then given 5 sessions of self-hypnosis training targeting their presenting symptoms. The findings supported the potential for both neurofeedback and mindfulness to enhance response to hypnosis treatment. Research using larger sample sizes to determine the generalizability of these findings is warranted.

Iron in Multiple Sclerosis and Its Noninvasive Imaging with Quantitative Susceptibility Mapping

PubMed Central

Stüber, Carsten; Pitt, David; Wang, Yi

2016-01-01

Iron is considered to play a key role in the development and progression of Multiple Sclerosis (MS). In particular, iron that accumulates in myeloid cells after the blood-brain barrier (BBB) seals may contribute to chronic inflammation, oxidative stress and eventually neurodegeneration. Magnetic resonance imaging (MRI) is a well-established tool for the non-invasive study of MS. In recent years, an advanced MRI method, quantitative susceptibility mapping (QSM), has made it possible to study brain iron through in vivo imaging. Moreover, immunohistochemical investigations have helped defining the lesional and cellular distribution of iron in MS brain tissue. Imaging studies in MS patients and of brain tissue combined with histological studies have provided important insights into the role of iron in inflammation and neurodegeneration in MS. PMID:26784172

Glomerular Filtration Rate in Patients with Multiple Sclerosis Undergoing Stem Cell Transplantation and Treated With Cyclophosphamide.

PubMed

Ruiz-Argüelles, Alejandro; Gastélum-Cano, Jose M; Méndez-Huerta, Mariana A; Rodríguez-Gallegos, Alma B; Ruiz-Argüelles, Guillermo J

2018-06-15

Glomerular filtration rate (GFR) is partially impaired in patients with multiple sclerosis (MS). When given chemotherapy before receiving hematopoietic stem-cell transplantation, GFR might be further deteriorated. To measure the effect of cyclophosphamide on GFR in patients with MS who undergo chemotherapy. We estimated GFR based on creatinine and cystatin C plasma concentrations in patients undergoing autologous hematopoietic stem-cell transplantation to treat their MS. Baseline GFR values were lower in the 28 patients with MS than in the 20 healthy individuals. Also, according to the Chronic Kidney Disease-Epidemiology Collaborative Group (CKD-EPI) 2012 Creat-CysC equation criteria, 4 of 28 patients were classified as having chronic kidney disease (CKD) before receiving the chemotherapy drugs. After receiving 4 × 50 mg per kg body weight cyclophosphamide, abnormal GFR results were recorded in 12 of 28 patients. Renal function must be monitored in patients with MS undergoing autologous stem-cell transplantation. Also, chemotherapy should be constrained as much as possible to prevent further deterioration of renal function.

Evaluation of the Effects of Sativex (THC BDS: CBD BDS) on Inhibition of Spasticity in a Chronic Relapsing Experimental Allergic Autoimmune Encephalomyelitis: A Model of Multiple Sclerosis

PubMed Central

Hilliard, A.; Stott, C.; Wright, S.; Guy, G.; Pryce, G.; Al-Izki, S.; Bolton, C.; Giovannoni, G.

2012-01-01

This study investigated the antispasticity potential of Sativex in mice. Chronic relapsing experimental allergic encephalomyelitis was induced in adult ABH mice resulting in hind limb spasticity development. Vehicle, Sativex, and baclofen (as a positive control) were injected intravenously and the “stiffness” of limbs assessed by the resistance force against hind limb flexion. Vehicle alone caused no significant change in spasticity. Baclofen (5 mg/kg) induced approximately a 40% peak reduction in spasticity. Sativex dose dependently reduced spasticity; 5 mg/kg THC + 5 mg/kg CBD induced approximately a 20% peak reduction; 10 mg/kg THC + 10 mg/kg CBD produced approximately a 40% peak reduction in spasticity. Sativex has the potential to reduce spasticity in an experimental mouse model of multiple sclerosis (MS). Baclofen reduced spasticity and served as a positive control. Sativex (10 mg/kg) was just as effective as baclofen, providing supportive evidence for Sativex use in the treatment of spasticity in MS. PMID:22928118

Multiple Sclerosis-related Uveitis: Does MS Treatment Affect Uveitis Course?

PubMed

Jouve, Léa; Benrabah, Rabah; Héron, Emmanuel; Bodaghi, Bahram; Le Hoang, Phuc; Touitou, Valérie

2017-06-01

Few data are available regarding the optimal treatment of multiple sclerosis (MS)-related uveitis. The aim of this study was to describe clinical features of MS-associated uveitis and determine how MS treatment affects the course of uveitis. Retrospective, multicenter study. Patients were divided into two groups according to the use (group 2) or not (group 1) of immunomodulatory drugs. Characteristics of uveitis and treatment were reviewed. A total of 68 eyes from 36 patients (17 in group 1 and 19 in group 2) were included. All patients were treated with topical and/or systemic steroids for uveitis. Uveitis occurred 1-17 years prior to neurologic symptoms in 78% of patients. Uveitis was more severe in group 2 (p<0.05), with a tendency toward a higher rate of chronic uveitis (p = 0.06). MS-related uveitis has often a favorable evolution. Patients on interferon-beta have more severe and chronic uveitis. As far as we are concerned, interferon-beta given on the sole indication of uveitis is not recommended. If steroid-sparing agent is required for intraocular inflammation, immunosuppressive drugs should be considered.

Quantitative susceptibility mapping (QSM) of white matter multiple sclerosis lesions: interpreting positive susceptibility and the presence of iron

PubMed Central

Wisnieff, Cynthia; Ramanan, Sriram; Olesik, John; Gauthier, Susan; Wang, Yi; Pitt, David

2014-01-01

Purpose Within multiple sclerosis (MS) lesions iron is present in chronically activated microglia. Thus, iron detection with MRI might provide a biomarker for chronic inflammation within lesions. Here, we examine contributions of iron and myelin to magnetic susceptibility of lesions on quantitative susceptibility mapping (QSM). Methods Fixed MS brain tissue was assessed with MRI including gradient echo data, which was processed to generate field (phase), R2* and QSM. Five lesions were sectioned and evaluated by immunohistochemistry for presence of myelin, iron and microglia/macrophages. Two of the lesions had an elemental analysis for iron concentration mapping, and their phospholipid content was estimated from the difference in the iron and QSM data. Results Three of the five lesions had substantial iron deposition that was associated with microglia and positive susceptibility values. For the two lesions with elemental analysis, the QSM derived phospholipid content maps were consistent with myelin labeled histology. Conclusion Positive susceptibility values with respect to water indicate the presence of iron in MS lesions, though both demyelination and iron deposition contribute to QSM. PMID:25137340

Consensus Recommendations of the Multiple Sclerosis Study Group and Portuguese Neuroradiological Society for the Use of the Magnetic Resonance Imaging in Multiple Sclerosis in Clinical Practice: Part 1.

PubMed

Abreu, Pedro; Pedrosa, Rui; Sá, Maria José; Cerqueira, João; Sousa, Lívia; Da Silva, Ana Martins; Pinheiro, Joaquim; De Sá, João; Batista, Sónia; Simões, Rita Moiron; Pereira, Daniela Jardim; Vilela, Pedro; Vale, José

2018-05-30

Magnetic resonance imaging is established as a recognizable tool in the diagnosis and monitoring of multiple sclerosis patients. In the present, among multiple sclerosis centers, there are different magnetic resonance imaging sequences and protocols used to study multiple sclerosis that may hamper the optimal use of magnetic resonance imaging in multiple sclerosis. In this context, the Group of Studies of Multiple Sclerosis and the Portuguese Society of Neuroradiology, after a joint discussion, appointed a committee of experts to create recommendations adapted to the national reality on the use of magnetic resonance imaging in multiple sclerosis. The purpose of this document is to publish the first Portuguese consensus recommendations on the use of magnetic resonance imaging in multiple sclerosis in clinical practice. The Group of Studies of Multiple Sclerosis and the Portuguese Society of Neuroradiology, after discussion of the topic in national meetings and after a working group meeting held in Figueira da Foz on May 2017, have appointed a committee of experts that have developed by consensus several standard protocols on the use of magnetic resonance imaging in the diagnosis and follow-up of multiple sclerosis. The document obtained was based on the best scientific evidence and expert opinion. Subsequently, the majority of Portuguese multiple sclerosis consultants and departments of neuroradiology scrutinized and reviewed the consensus paper; comments and suggestions were considered. Technical magnetic resonance imaging protocols regarding diagnostic, monitoring and the recommended information to be included in the magnetic resonance imaging report will be published in a separate paper. We provide some practical guidelines to promote standardized strategies to be applied in the clinical practice setting of Portuguese healthcare professionals regarding the use of magnetic resonance imaging in multiple sclerosis. We hope that these first Portuguese magnetic resonance imaging guidelines, based in the best available clinical evidence and practices, will serve to optimize multiple sclerosis management and improve multiple sclerosis patient care across Portugal.

Relationships between trunk performance, gait and postural control in persons with multiple sclerosis.

PubMed

Freund, Jane E; Stetts, Deborah M; Vallabhajosula, Srikant

2016-06-30

Multiple sclerosis (MS) is a chronic progressive disease of the central nervous system. Compared to healthy individuals, persons with multiple sclerosis (PwMS) have increased postural sway in quiet stance, decreased gait speed and increased fall incidence. Trunk performance has been implicated in postural control, gait dysfunction, and fall prevention in older adults. However, the relationship of trunk performance to postural control and gait has not been adequately studied in PwMS. To compare trunk muscle structure and performance in PwMS to healthy age and gendered-matched controls (HC); to determine the effects of isometric trunk endurance testing on postural control in both populations; and to determine the relationship of trunk performance with postural control, gait and step activity in PwMS. Fifteen PwMS and HC completed ultrasound imaging of trunk muscles, 10 m walk test, isometric trunk endurance tests, and postural sway test. Participants wore a step activity monitor for 7 days. PwMS had worse isometric trunk endurance compared to HC. PwMS trunk flexion endurance negatively correlated to several postural control measures and positively correlated to gait speed and step activity. Clinicians should consider evaluation and interventions directed at impaired trunk endurance in PwMS.

Therapeutic decision making in a new drug era in multiple sclerosis.

PubMed

Keegan, B Mark

2013-02-01

Multiple sclerosis is a presumed autoimmune, inflammatory disease of the central nervous system. Since the early 1990s, medications have been devised, tested, and approved for relapsing forms of multiple sclerosis (MS). MS treatments work by altering the immune system to reduce inflammatory MS activity, thus curtailing clinical relapses (attacks), thereby reducing short-term disability related to the MS attacks. The promise of long-term improvement in MS-related disability remains the most desirable therapeutic goal; to what degree current MS therapies are effective in reducing this is controversial. Recent years have seen a surge in novel MS therapies delivered both parenterally and orally that offer new therapeutic alternatives to MS patients and their treating providers. It remains essential to make an unequivocal diagnosis of MS and identify its clinical course prior to initiating therapies. Switching and altering MS therapies can now be done by rational approaches based on therapeutic efficacy and tolerability; however, these remain nonevidence-based for the most part. The high cost of MS therapies remains a significant concern. A new therapeutic era is at hand offering new hope for patients affected by this chronic, frequently disabling disease. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Cyclic phosphatidic acid treatment suppress cuprizone-induced demyelination and motor dysfunction in mice.

PubMed

Yamamoto, Shinji; Gotoh, Mari; Kawamura, Yuuki; Yamashina, Kota; Yagishita, Sosuke; Awaji, Takeo; Tanaka, Motomu; Maruyama, Kei; Murakami-Murofushi, Kimiko; Yoshikawa, Keisuke

2014-10-15

Multiple sclerosis is a chronic demyelinating disease of the central nervous system leading to progressive cognitive and motor dysfunction, which is characterized by neuroinflammation, demyelination, astrogliosis, loss of oligodendrocytes, and axonal pathologies. Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator with a unique cyclic phosphate ring structure at the sn-2 and sn-3 positions of the glycerol backbone. cPA elicits a neurotrophin-like action and protects hippocampal neurons from ischemia-induced delayed neuronal death. In this study, we investigated the effects of cPA on cuprizone-induced demyelination, which is a model of multiple sclerosis. Mice were fed a diet containing 0.2% cuprizone for 5 weeks, which induces severe demyelination, astrocyte and microglial activation, and motor dysfunction. Simultaneous administration of cPA effectively attenuated cuprizone-induced demyelination, glial activation, and motor dysfunction. These data indicate that cPA may be a useful treatment to reduce the extent of demyelination and the severity of motor dysfunction in multiple sclerosis. cPA is a potential lead compound in the development of drugs for the treatment of this devastating disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Exploring the facilitators and barriers to engagement in physical activity for people with multiple sclerosis.

PubMed

Kayes, Nicola M; McPherson, Kathryn M; Schluter, Philip; Taylor, Denise; Leete, Marta; Kolt, Gregory S

2011-01-01

To explore the relationship that cognitive behavioural and other previously identified variables have with physical activity engagement in people with multiple sclerosis (MS). This study adopted a cross-sectional questionnaire design. Participants were 282 individuals with MS. Outcome measures included the Physical Activity Disability Survey--Revised, Cognitive and Behavioural Responses to Symptoms Questionnaire, Barriers to Health Promoting Activities for Disabled Persons Scale, Multiple Sclerosis Self-efficacy Scale, Self-Efficacy for Chronic Diseases Scales and Chalder Fatigue Questionnaire. Multivariable stepwise regression analyses found that greater self-efficacy, greater reported mental fatigue and lower number of perceived barriers to physical activity accounted for a significant proportion of variance in physical activity behaviour, over that accounted for by illness-related variables. Although fear-avoidance beliefs accounted for a significant proportion of variance in the initial analyses, its effect was explained by other factors in the final multivariable analyses. Self-efficacy, mental fatigue and perceived barriers to physical activity are potentially modifiable variables which could be incorporated into interventions designed to improve physical activity engagement. Future research should explore whether a measurement tool tailored to capture beliefs about physical activity identified by people with MS would better predict participation in physical activity.

Upper Extremity Function in Multiple Sclerosis Patients With Advanced Disability Treated With Ocrevus

ClinicalTrials.gov

2018-06-18

Multiple Sclerosis; Pathologic Processes; Demyelinating Diseases; Demyelinating Autoimmune Diseases; Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Primary Progressive Multiple Sclerosis; Relapsing Remitting Multiple Sclerosis

The natural history of multiple sclerosis: a geographically based study. 5. The clinical features and natural history of primary progressive multiple sclerosis.

PubMed

Cottrell, D A; Kremenchutzky, M; Rice, G P; Koopman, W J; Hader, W; Baskerville, J; Ebers, G C

1999-04-01

We report a natural history study of 216 patients with primary progressive (PP)- multiple sclerosis defined by at least 1 year of exacerbation-free progression at onset. This represents 19.8% of a largely population-based patient cohort having a mean longitudinal follow-up of 23 years. This subgroup of PP-multiple sclerosis patients had a mean age of onset of 38.5 years, with females predominating by a ratio of 1.3:1.0. The rate of deterioration from disease onset was substantially more rapid than for relapsing-remitting multiple sclerosis, with a median time to disability status score (DSS) 6 and DSS 8 of 8 and 18 years, respectively. Forty-nine percent of patients were followed through to death. Examination of the early disease course revealed two groups with adverse prognostic profiles. Firstly, a shorter time to reach DSS 3 from onset of PP-multiple sclerosis significantly adversely influenced time to DSS 8. Second, involvement of three or more neurological systems at onset resulted in a median time to DSS 10 of 13.5 years in contrast to PP-multiple sclerosis patients with one system involved at onset where median time to death from multiple sclerosis was 33.2 years. However, age, gender and type of neurological system involved at onset appeared to have little influence on prognosis. Life expectancy, cause of mortality and familial history profile were similar in PP-multiple sclerosis and non-PP-multiple sclerosis (all other multiple sclerosis patients from the total population). From clinical onset, rate of progression was faster in the PP-multiple sclerosis group than in the secondary progressive (SP)-multiple sclerosis group. When the rates of progression from onset of the progressive phase to DSS 6, 8 and 10 were compared, SP-multiple sclerosis had a more rapid progressive phase. A substantial minority (28%) of the PP-multiple sclerosis cohort had a distinct relapse even decades after onset of progressive deterioration. These studies establish natural history outcomes for the subgroup of multiple sclerosis patients with primary progressive disease.

[Sacral neuromodulation as second-line treatment strategy for lower urinary tract symptoms of various aetiologies: experience of a German high-volume clinic].

PubMed

Otto, W; Nowrotek, A; Burger, M; Wieland, W F; Rößler, W; Denzinger, S

2012-05-01

Lower urinary tract symptoms (LUTS) are a common and multiform micturition disorder of various possible origins. Several second-line techniques are available in the event of first-line medicinal treatment failure. These include the intravesical injection of Botulinum toxin, bladder augmentation and sacral neuromodulation (SNM). This study presents current data and results from a prospective study of patients with LUTS of various aetiologies. Clinical success was investigated for all patients who underwent SNM for LUTS with or without urge incontinence caused by chronic pelvic pain syndrome, multiple sclerosis and idiopathic disease between May 2007 and December 2010. The preoperatively determined symptoms were compared with current follow-up data. Median follow-up time was 11 months (1 - 43). A total of 47 patients were indicated for SNM over the investigated period. 80.9 % were female, median patient age was 67 years (19 - 84). The testing phase was successful in 38 cases (80.9 %) with 9 electrodes being explanted (19.1 %). In the case of idiopathic LUTS we could show a statistically significant increase of micturition volume and reduction of incontinence pad use. There was no statistically significant improvement of any micturition parameter for patients with multiple sclerosis, patients with chronic pelvic pain syndrome showed a statistically significant reduction of micturition frequency and a subjective improvement of symptoms in 75 %. In the selected patient groups SNM is a promising and, in experienced hands, a low-complication second-line therapy for the treatment of LUTS of idiopathic aetiology. However, the general recommendation of SNM for multiple sclerosis and chronic pelvic pain syndrome patients cannot be given on the basis of our results. Further prospective, randomised multicentre studies are need to further refine the indications for SNM in LUTS of neurogenic and non-neurogenic origins. © Georg Thieme Verlag KG Stuttgart · New York.

Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function.

PubMed

Ontaneda, Daniel; Thompson, Alan J; Fox, Robert J; Cohen, Jeffrey A

2017-04-01

Multiple sclerosis is a major cause of neurological disability, which accrues predominantly during progressive forms of the disease. Although development of multifocal inflammatory lesions is the underlying pathological process in relapsing-remitting multiple sclerosis, the gradual accumulation of disability that characterises progressive multiple sclerosis seems to result more from diffuse immune mechanisms and neurodegeneration. As a result, the 14 anti-inflammatory drugs that have regulatory approval for treatment of relapsing-remitting multiple sclerosis have little or no efficacy in progressive multiple sclerosis without inflammatory lesion activity. Effective therapies for progressive multiple sclerosis that prevent worsening, reverse damage, and restore function are a major unmet need. In this Series paper we summarise the current status of therapy for progressive multiple sclerosis and outline prospects for the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

A combined post-mortem magnetic resonance imaging and quantitative histological study of multiple sclerosis pathology

PubMed Central

Kolasinski, James; Chance, Steven A.; DeLuca, Gabriele C.; Esiri, Margaret M.; Chang, Eun-Hyuk; Palace, Jacqueline A.; McNab, Jennifer A.; Jenkinson, Mark; Miller, Karla L.; Johansen-Berg, Heidi

2012-01-01

Multiple sclerosis is a chronic inflammatory neurological condition characterized by focal and diffuse neurodegeneration and demyelination throughout the central nervous system. Factors influencing the progression of pathology are poorly understood. One hypothesis is that anatomical connectivity influences the spread of neurodegeneration. This predicts that measures of neurodegeneration will correlate most strongly between interconnected structures. However, such patterns have been difficult to quantify through post-mortem neuropathology or in vivo scanning alone. In this study, we used the complementary approaches of whole brain post-mortem magnetic resonance imaging and quantitative histology to assess patterns of multiple sclerosis pathology. Two thalamo-cortical projection systems were considered based on their distinct neuroanatomy and their documented involvement in multiple sclerosis: lateral geniculate nucleus to primary visual cortex and mediodorsal nucleus of the thalamus to prefrontal cortex. Within the anatomically distinct thalamo-cortical projection systems, magnetic resonance imaging derived cortical thickness was correlated significantly with both a measure of myelination in the connected tract and a measure of connected thalamic nucleus cell density. Such correlations did not exist between these markers of neurodegeneration across different thalamo-cortical systems. Magnetic resonance imaging lesion analysis depicted clearly demarcated subcortical lesions impinging on the white matter tracts of interest; however, quantitation of the extent of lesion-tract overlap failed to demonstrate any appreciable association with the severity of markers of diffuse pathology within each thalamo-cortical projection system. Diffusion-weighted magnetic resonance imaging metrics in both white matter tracts were correlated significantly with a histologically derived measure of tract myelination. These data demonstrate for the first time the relevance of functional anatomical connectivity to the spread of multiple sclerosis pathology in a ‘tract-specific’ pattern. Furthermore, the persisting relationship between metrics from post-mortem diffusion-weighted magnetic resonance imaging and histological measures from fixed tissue further validates the potential of imaging for future neuropathological studies. PMID:23065787

Comparison of quality of life between two clinical conditions with immunosuppressive therapy: liver transplantation and multiple sclerosis.

PubMed

Fernández-Jiménez, E; Pérez-San-Gregorio, M A; Martín-Rodríguez, A; Domínguez-Cabello, E; Navarro-Mascarell, G; Bernardos-Rodríguez, A

2012-11-01

We aimed to compare quality of life in two clinical conditions treated with immunosuppressants: cadaveric liver transplant recipients and multiple sclerosis patients. We also assessed the clinical significance of these results regarding a representative age-adjusted sample of the general Spanish population. Using a cross-sectional design, the SF-36 Health Survey was used to evaluate 62 patients with these chronic conditions (31 in each group) who were matched for gender. An analysis of covariance was performed to control for the influence of time from multiple sclerosis diagnosis and liver transplantation surgery until assessment. Student t test of covariate-adjusted mean values was used as the statistical test and Cohen's d effect size index, to assess the magnitude of intergroup differences and assess clinical significance. Significantly worse scores were observed among the neurological patients compared with transplant recipients regarding role-physical (P = .038), general health (P = .003), vitality (P = .034), and physical functioning (P = .049), with medium effect sizes (Cohen's ds from -0.511 to -0.785). Against normative values, liver transplant recipients displayed relevant differences in all SF-36 subscales (Cohen's ds from -0.569 to -0.974) except for mental health (small effect size). Likewise, multiple sclerosis patients showed much greater differences versus the general population (Cohen's ds from -0.846 to -1.760). Liver transplant recipients showed better quality of life than multiple sclerosis patients (medium effect sizes) in physical quality-of-life dimensions. Interestingly, despite having controlled for time from diagnosis/transplantation, both medical conditions showed clinically significant impairments (large and medium effect sizes) in physical and psychosocial quality-of-life domains. We concluded that transplant recipients belong to a population that still requires special health care because, even after having undergone their treatment of choice, they do not achieve normal levels of biopsychosocial functioning. Copyright © 2012 Elsevier Inc. All rights reserved.

Treatment of Cognitive Impairment in Multiple Sclerosis

PubMed Central

Pierson, Susan H.; Griffith, Nathan

2006-01-01

Cognitive impairment in multiple sclerosis is an increasingly recognized entity. This article reviews the cognitive impairment of multiple sclerosis, its prevalence, its relationship to different types of multiple sclerosis, and its contribution to long-term functional prognosis. The discussion also focuses on the key elements of cognitive dysfunction in multiple sclerosis which distinguish it from other forms of cognitive impairment. Therapeutic interventions potentially effective for the cognitive impairment of multiple sclerosis are reviewed including the effects of disease modifying therapies and the use of physical and cognitive interventions. PMID:16720960

The Effect of Orem’s Self-Care Model on Fatigue in Patients With Multiple Sclerosis: A Single Blind Randomized Clinical Trial Study

PubMed Central

Afrasiabifar, Ardashir; Mehri, Zahra; Javad Sadat, Saied; Ghaffarian Shirazi, Hamid Reza

2016-01-01

Background Orem’s self-care model is a nursing model that was introduced with the purpose of improving the self-care of individuals, especially patients suffering from chronic diseases. Objectives To determining the effect of Orem’s self-care model on fatigue in multiple sclerosis patients. Patients and Methods This research involved a clinical trial. Sixty-three multiple sclerosis patients at the vice-chancellor in treatment affairs of Yasuj University of Medical Sciences were selected based on nonrandom sampling, but they were allocated to the two groups based on random allocation. In the intervention group, Orem’s model was applied during six sessions of 45 - 60 minutes in length, and the process continued for 1 month. The data were collected 1 week before and 7 weeks after the end of the intervention using the Orem’s self-care model-based assessment form and fatigue severity scale, the validity and reliability of which have been Results Before the intervention, 11.11% of the participants had a good knowledge of self-care. In addition, self-care willingness and skills were observed in 76.19% and 4.76% of participants, respectively. The mean difference in fatigue reduced significantly in the intervention group after the intervention (P < 0.05). After the intervention, a statistically significant difference was observed in the mean difference of fatigue between the two groups (P < 0.05). Conclusions Orem’s self-care model is significantly effective in reducing the fatigue of multiple sclerosis patients. PMID:27781119

Sequencing of disease-modifying therapies for relapsing-remitting multiple sclerosis: a theoretical approach to optimizing treatment.

PubMed

Grand'Maison, Francois; Yeung, Michael; Morrow, Sarah A; Lee, Liesly; Emond, Francois; Ward, Brian J; Laneuville, Pierre; Schecter, Robyn

2018-04-18

Multiple sclerosis (MS) is a chronic disease which usually begins in young adulthood and is a lifelong condition. Individuals with MS experience physical and cognitive disability resulting from inflammation and demyelination in the central nervous system. Over the past decade, several disease-modifying therapies (DMTs) have been approved for the management of relapsing-remitting MS (RRMS), which is the most prevalent phenotype. The chronic nature of the disease and the multiple treatment options make benefit-risk-based sequencing of therapy essential to ensure optimal care. The efficacy and short- and long-term risks of treatment differ for each DMT due to their different mechanism of action on the immune system. While transitioning between DMTs, in addition to immune system effects, factors such as age, disease duration and severity, disability status, monitoring requirements, preference for the route of administration, and family planning play an important role. Determining a treatment strategy is therefore challenging as it requires careful consideration of the differences in efficacy, safety and tolerability, while at the same time minimizing risks of immune modulation. In this review, we discuss a sequencing approach for treating RRMS, with importance given to the long-term risks and individual preference when devising a treatment plan. Evidence-based strategies to counter breakthrough disease are also addressed.

Supratentorial lesions contribute to trigeminal neuralgia in multiple sclerosis.

PubMed

Fröhlich, Kilian; Winder, Klemens; Linker, Ralf A; Engelhorn, Tobias; Dörfler, Arnd; Lee, De-Hyung; Hilz, Max J; Schwab, Stefan; Seifert, Frank

2018-06-01

Background It has been proposed that multiple sclerosis lesions afflicting the pontine trigeminal afferents contribute to trigeminal neuralgia in multiple sclerosis. So far, there are no imaging studies that have evaluated interactions between supratentorial lesions and trigeminal neuralgia in multiple sclerosis patients. Methods We conducted a retrospective study and sought multiple sclerosis patients with trigeminal neuralgia and controls in a local database. Multiple sclerosis lesions were manually outlined and transformed into stereotaxic space. We determined the lesion overlap and performed a voxel-wise subtraction analysis. Secondly, we conducted a voxel-wise non-parametric analysis using the Liebermeister test. Results From 12,210 multiple sclerosis patient records screened, we identified 41 patients with trigeminal neuralgia. The voxel-wise subtraction analysis yielded associations between trigeminal neuralgia and multiple sclerosis lesions in the pontine trigeminal afferents, as well as larger supratentorial lesion clusters in the contralateral insula and hippocampus. The non-parametric statistical analysis using the Liebermeister test yielded similar areas to be associated with multiple sclerosis-related trigeminal neuralgia. Conclusions Our study confirms previous data on associations between multiple sclerosis-related trigeminal neuralgia and pontine lesions, and showed for the first time an association with lesions in the insular region, a region involved in pain processing and endogenous pain modulation.

Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding Chronic Active Lesions

PubMed Central

Hendrickx, Debbie A. E.; van Scheppingen, Jackelien; van der Poel, Marlijn; Bossers, Koen; Schuurman, Karianne G.; van Eden, Corbert G.; Hol, Elly M.; Hamann, Jörg; Huitinga, Inge

2017-01-01

In multiple sclerosis (MS), activated microglia and infiltrating macrophages phagocytose myelin focally in (chronic) active lesions. These demyelinating sites expand in time, but at some point turn inactive into a sclerotic scar. To identify molecular mechanisms underlying lesion activity and halt, we analyzed genome-wide gene expression in rim and peri-lesional regions of chronic active and inactive MS lesions, as well as in control tissue. Gene clustering revealed patterns of gene expression specifically associated with MS and with the presumed, subsequent stages of lesion development. Next to genes involved in immune functions, we found regulation of novel genes in and around the rim of chronic active lesions, such as NPY, KANK4, NCAN, TKTL1, and ANO4. Of note, the presence of many foamy macrophages in active rims was accompanied by a congruent upregulation of genes related to lipid binding, such as MSR1, CD68, CXCL16, and OLR1, and lipid uptake, such as CHIT1, GPNMB, and CCL18. Except CCL18, these genes were already upregulated in regions around active MS lesions, showing that such lesions are indeed expanding. In vitro downregulation of the scavenger receptors MSR1 and CXCL16 reduced myelin uptake. In conclusion, this study provides the gene expression profile of different aspects of MS pathology and indicates that early demyelination, mediated by scavenger receptors, is already present in regions around active MS lesions. Genes involved in early demyelination events in regions surrounding chronic active MS lesions might be promising therapeutic targets to stop lesion expansion. PMID:29312322

Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding Chronic Active Lesions.

PubMed

Hendrickx, Debbie A E; van Scheppingen, Jackelien; van der Poel, Marlijn; Bossers, Koen; Schuurman, Karianne G; van Eden, Corbert G; Hol, Elly M; Hamann, Jörg; Huitinga, Inge

2017-01-01

In multiple sclerosis (MS), activated microglia and infiltrating macrophages phagocytose myelin focally in (chronic) active lesions. These demyelinating sites expand in time, but at some point turn inactive into a sclerotic scar. To identify molecular mechanisms underlying lesion activity and halt, we analyzed genome-wide gene expression in rim and peri-lesional regions of chronic active and inactive MS lesions, as well as in control tissue. Gene clustering revealed patterns of gene expression specifically associated with MS and with the presumed, subsequent stages of lesion development. Next to genes involved in immune functions, we found regulation of novel genes in and around the rim of chronic active lesions, such as NPY, KANK4, NCAN, TKTL1 , and ANO4 . Of note, the presence of many foamy macrophages in active rims was accompanied by a congruent upregulation of genes related to lipid binding, such as MSR1, CD68, CXCL16 , and OLR1 , and lipid uptake, such as CHIT1, GPNMB , and CCL18 . Except CCL18 , these genes were already upregulated in regions around active MS lesions, showing that such lesions are indeed expanding. In vitro downregulation of the scavenger receptors MSR1 and CXCL16 reduced myelin uptake. In conclusion, this study provides the gene expression profile of different aspects of MS pathology and indicates that early demyelination, mediated by scavenger receptors, is already present in regions around active MS lesions. Genes involved in early demyelination events in regions surrounding chronic active MS lesions might be promising therapeutic targets to stop lesion expansion.

Heat Shock Protein 70: Roles in Multiple Sclerosis

PubMed Central

Mansilla, María José; Montalban, Xavier; Espejo, Carmen

2012-01-01

Heat shock proteins (HSP) have long been considered intracellular chaperones that possess housekeeping and cytoprotective functions. Consequently, HSP overexpression was proposed as a potential therapy for neurodegenerative diseases characterized by the accumulation or aggregation of abnormal proteins. Recently, the discovery that cells release HSP with the capacity to trigger proinflammatory as well as immunoregulatory responses has focused attention on investigating the role of HSP in chronic inflammatory autoimmune diseases such as multiple sclerosis (MS). To date, the most relevant HSP is the inducible Hsp70, which exhibits both cytoprotectant and immunoregulatory functions. Several studies have presented contradictory evidence concerning the involvement of Hsp70 in MS or experimental autoimmune encephalomyelitis (EAE), the MS animal model. In this review, we dissect the functions of Hsp70 and discuss the controversial data concerning the role of Hsp70 in MS and EAE. PMID:22669475

Orthodontic treatment for a patient with multiple sclerosis

PubMed Central

Bakathir, Manal A

2017-01-01

Multiple sclerosis (MS) is a chronic, autoimmune inflammatory disorder of the central nervous system (CNS) that affects myelinated axons, destroying the myelin and damaging axons to varying degrees. The course of MS is highly varied and unpredictable. Metals used during orthodontic treatment can negatively affect imaging techniques used to diagnose and monitor the progression of MS, while medications used to treat MS can negatively affect orthodontic tooth movement. The present case report highlights some of the challenges encountered during orthodontic treatment of a patient with MS and how to overcome them. The patient was a 20-year-old woman with complaints of diastema and spacing in the upper arch. Although closing the spaces was challenging due to some of the MS medications, she was treated successfully, without complications, within 20 months using closing loops. PMID:28717636

Positive or negative involvement of heat shock proteins in multiple sclerosis pathogenesis: an overview.

PubMed

Turturici, Giuseppina; Tinnirello, Rosaria; Sconzo, Gabriella; Asea, Alexzander; Savettieri, Giovanni; Ragonese, Paolo; Geraci, Fabiana

2014-12-01

Multiple sclerosis (MS) is the most diffuse chronic inflammatory disease of the central nervous system. Both immune-mediated and neurodegenerative processes apparently play roles in the pathogenesis of this disease. Heat shock proteins (HSPs) are a family of highly evolutionarily conserved proteins; their expression in the nervous system is induced in a variety of pathologic states, including cerebral ischemia, neurodegenerative diseases, epilepsy, and trauma. To date, investigators have observed protective effects of HSPs in a variety of brain disease models (e.g. of Alzheimer disease and Parkinson disease). In contrast, unequivocal data have been obtained for their roles in MS that depend on the HSP family and particularly on their localization (i.e. intracellular or extracellular). This article reviews our current understanding of the involvement of the principal HSP families in MS.

[Chronically ill and unemployed? A review on vocational status in multiple sclerosis].

PubMed

Kern, S; Kühn, M; Ziemssen, T

2013-02-01

Multiple sclerosis (MS) is one of the most common neurological disorders in young adults. It is characterised by a chronic progressive course with far reaching implications on the patient's private and professional life. Based on the current literature, employment status is analysed in relation to disease-specific, therapeutic, psychosocial, and socioeconomic factors. A special emphasis is placed on the vocational status of MS patients in Germany. According national and international studies, around 40 % of all MS patients are currently unemployed. Main reasons for early retirement are disease-specific factors such as impaired mobility, disability in the upper extremities, fatigue, and cognitive impairment. According to the German Multiple Sclerosis Registry (GMSR), these symptoms are still insufficiently treated. In patients with minor motoric impairment (EDSS ≤ 3.0), depressive symptoms seem to have a major impact on employment status. Disease progression, older age at diagnosis, and hard physical work are negative predictors in terms of employment situation. The lack of flexible working hours, the inability to have flexible resting times at work, a lack of understanding from colleagues and employers as well as the personal attitude were main non-disease-specific reasons for early retirement. The current knowledge on the vocational status in MS is mainly based on international studies (e. g., Scandinavia, England, USA, Australia, MSIF Survey). For Germany, only the GMSR supports significant information on the employment status of MS patients. According to the GMSR, ataxia, fatigue and cognitive dysfunction are still insufficiently treated - a situation that is at least partly due to insufficient treatment options. Comprehensive studies that focus on a broad range of possible influencing factors on vocational status of German MS patients are currently lacking. © Georg Thieme Verlag KG Stuttgart · New York.

Total lymphoid irradiation for multiple sclerosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Devereux, C.K.; Vidaver, R.; Hafstein, M.P.

1988-01-01

Although chemical immunosuppression has been shown to benefit patients with chronic progressive multiple sclerosis (MS), it appears that chemotherapy has an appreciable oncogenic potential in patients with multiple sclerosis. Accordingly, we developed a modified total lymphoid irradiation (TLI) regimen designed to reduce toxicity and applied it to a randomized double blind trial of TLI or sham irradiation in MS. Standard TLI regimens were modified to reduce dose to 1,980 rad, lowering the superior mantle margin to midway between the thyroid cartilage and angle of the mandible (to avert xerostomia) and the lower margin of the mantle field to the inferiormore » margin of L1 (to reduce gastrointestinal toxicity by dividing abdominal radiation between mantle and inverted Y), limiting spinal cord dose to 1,000 rad by custom-made spine blocks in the mantle and upper 2 cm of inverted Y fields, and also protecting the left kidney even if part of the spleen were shielded. Clinical efficacy was documented by the less frequent functional scale deterioration of 20 TLI treated patients with chronic progressive MS compared to to 20 sham-irradiated progressive MS patients after 12 months (16% versus 55%, p less than 0.03), 18 months (28% versus 63%, p less than 0.03), and 24 months (44% versus 74%, N.S.). Therapeutic benefit during 3 years follow-up was related to the reduction in lymphocyte count 3 months post-irradiation (p less than 0.02). Toxicity was generally mild and transient, with no instance of xerostomia, pericarditis, herpes zoster, or need to terminate treatment in TLI patients. However, menopause was induced in 2 patients and staphylococcal pneumonia in one.« less

Prevalence of Extracranial Venous Narrowing on Magnetic Resonance Venography Is Similar in People With Multiple Sclerosis, Their Siblings, and Unrelated Healthy Controls: A Blinded, Case-Control Study.

PubMed

Martin, Nancy; Traboulsee, Anthony L; Machan, Lindsay; Klass, Darren; Ellchuk, Tasha; Zhao, Yinshan; Knox, Katherine B; Kopriva, David; Lala, Shantilal; Nickel, Darren; Otani, Robert; Perera, Warren R; Rauscher, Alexander; Sadovnick, A Dessa; Szkup, Peter; Li, David K

2017-05-01

The study sought to assess and compare the prevalence of narrowing of the major extracranial veins in subjects with multiple sclerosis and controls, and to assess the sensitivity and specificity of magnetic resonance venography (MRV) for describing extracranial venous narrowing as it applies to the chronic cerebrospinal venous insufficiency theory, using catheter venography (CV) as the gold standard. The jugular and azygos veins were assessed with time-of-flight MRV in this assessor-blinded, case-control study of subjects with multiple sclerosis, their unaffected siblings, and unrelated controls. The veins were evaluated by diameter and area, and compared with CV. Collateral vessels were also analyzed for maximal diameter, as a potential indicator of compensatory flow. A high prevalence of extracranial venous narrowing was demonstrated in all study groups, collectively up to 84% by diameter criteria and 90% by area, with no significant difference between the groups when assessed independently (P = .34 and .63, respectively). There was high interobserver variability in the reporting of vessel narrowing (kappa = 0.32), and poor vessel per vessel correlation between narrowing on MRV and CV (kappa = 0.064). Collateral neck veins demonstrated no convincing difference in maximum size or correlation with jugular narrowing. There is a high prevalence of narrowing of the major extracranial veins on MRV in all 3 study groups, with no significant difference between them. These findings do not support the chronic cerebrospinal venous insufficiency theory. Although MRV has shown a high sensitivity for identifying venous narrowing, time-of-flight imaging demonstrates poor interobserver agreement and poor specificity when compared with the gold standard CV. Copyright © 2016 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

An endovascular treatment of Chronic Cerebro-Spinal Venous Insufficiency in multiple sclerosis patients - 6 month follow-up results.

PubMed

Kostecki, Jacek; Zaniewski, Maciej; Ziaja, Krzysztof; Urbanek, Tomasz; Kuczmik, Waclaw; Krzystanek, Ewa; Ziaja, Damian; Korzeniowski, Tomasz; Majewski, Eugeniusz; Hartel, Marcin; Swiat, Maciej; Sioma-Markowska, Urszula

2011-01-01

In this study, the mid-term results (6 month follow-up) of the endovascular treatment in patients with Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) and multiple sclerosis (MS) were prospectively evaluated. Thirty-six patients with confirmed MS and CCSVI underwent endovascular treatment by the means of the uni- or bilateral jugular vein angioplasty with optional stent placement. All the patients completed 6 month follow-up. Their MS-related disability status and quality of life were evaluated 1, 3 and 6 months postoperatively by means of the following scales: Expanded Disability Status Scale (EDSS), Multiple Sclerosis Impact Scale (MSIS-29), Epworth Sleepiness Scale (ESS), Heat Intolerance scale (HIS) and Fatigue Severity Scale (FSS). For patency and restenosis rate assessment, the control US duplex Doppler examination was used. Six months after the procedure, restenosis in post-PTA jugular veins was found in 33% of cases. Among 17 patients who underwent stent implantation into the jugular vein, restenosis or partial in-stent thrombosis was identified in 55% of the cases. At the 6 month follow-up appointment, there was no significant improvement in the EDSS or the ESS. The endovascular treatment of the CCSVI improved the quality of life according to the MSIS-29 scale but only up to 3 months after the procedure (with no differences in the 6 month follow-up assessment). Six months after the jugular vein angioplasty (with or without stent placement), a statistically significant improvement was observed only in the FSS and the HIS. The endovascular treatment in patients with MS and concomitant CCSVI did not have an influence on the patient's neurological condition; however, in the mid-term follow-up, an improvement in some quality-of-life parameters was observed.

Disease-modifying treatments for early and advanced multiple sclerosis: a new treatment paradigm.

PubMed

Giovannoni, Gavin

2018-06-01

The treatment of multiple sclerosis is evolving rapidly with 11 classes of disease-modifying therapies (DMTs). This article provides an overview of a new classification system for DMTs and treatment paradigm for using these DMTs effectively and safely. A summary of research into the use of more active approaches to early and effective treatment of multiple sclerosis with defined treatment targets of no evident disease activity (NEDA). New insights are discussed that is allowing the field to begin to tackle more advanced multiple sclerosis, including people with multiple sclerosis using wheelchairs. However, the need to modify expectations of what can be achieved in more advanced multiple sclerosis are discussed; in particular, the focus on neuronal systems with reserve capacity, for example, upper limb, bulbar and visual function. The review describes a new more active way of managing multiple sclerosis and concludes with a call to action in solving the problem of slow adoption of innovations and the global problem of untreated, or undertreated, multiple sclerosis.

Does vagotomy protect against multiple sclerosis?

PubMed

Sundbøll, Jens; Horváth-Puhó, Erzsébet; Adelborg, Kasper; Svensson, Elisabeth

2017-07-01

To examine the association between vagotomy and multiple sclerosis. We conducted a matched cohort study of all patients who underwent truncal or super-selective vagotomy and a comparison cohort, by linking Danish population-based medical registries (1977-1995). Hazard ratios (HRs) for multiple sclerosis, adjusting for potential confounders were computed by means of Cox regression analysis. Median age of multiple sclerosis onset corresponded to late onset multiple sclerosis. No association with multiple sclerosis was observed for truncal vagotomy (0-37 year adjusted HR=0.91, 95% confidence interval [CI]: 0.48-1.74) or super-selective vagotomy (0-37 year adjusted HR=1.28, 95% CI: 0.79-2.09) compared with the general population. We found no association between vagotomy and later risk of late onset multiple sclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Which symptoms contribute the most to patients' perception of health in multiple sclerosis?

PubMed

Green, Rivka; Cutter, Gary; Friendly, Michael; Kister, Ilya

2017-01-01

Multiple sclerosis is a polysymptomatic disease. Little is known about relative contributions of the different multiple sclerosis symptoms to self-perception of health. To investigate the relationship between symptom severity in 11 domains affected by multiple sclerosis and self-rated health. Multiple sclerosis patients in two multiple sclerosis centers assessed self-rated health with a validated instrument and symptom burden with symptoMScreen, a validated battery of Likert scales for 11 domains commonly affected by multiple sclerosis. Pearson correlations and multivariate linear regressions were used to investigate the relationship between symptoMScreen scores and self-rated health. Among 1865 multiple sclerosis outpatients (68% women, 78% with relapsing-remitting multiple sclerosis, mean age 46.38 ± 12.47 years, disease duration 13.43 ± 10.04 years), average self-rated health score was 2.30 ('moderate to good'). Symptom burden (composite symptoMScreen score) highly correlated with self-rated health ( r  = 0.68, P  < 0.0001) as did each of the symptoMScreen domain subscores. In regression analysis, pain ( t  = 7.00), ambulation ( t  = 6.91), and fatigue ( t  = 5.85) contributed the highest amount of variance in self-rated health ( P  < 0.001). Pain contributed the most to multiple sclerosis outpatients' perception of health, followed by gait dysfunction and fatigue. These findings suggest that 'invisible disability' may be more important to patients' sense of wellbeing than physical disability, and challenge the notion that physical disability should be the primary outcome measure in multiple sclerosis.

Effectiveness of multiple sclerosis treatment with current immunomodulatory drugs.

PubMed

Milo, Ron

2015-04-01

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS of a putative autoimmune origin characterized by neurologic dysfunction disseminated in space and time due to demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of the disease resulted in the introduction of numerous effective immunomodulatoty drugs having diverse mechanisms of action, modes of administration and risk-benefit profiles. This results in more complex albeit more promising treatment selection and choices. The epidemiology, clinical features, pathogenesis and diagnosis of the disease are discussed. The mode of action and main characteristics of current immunomodulatory drugs for MS and their place in the therapeutic algorithm of the disease based on evidence from clinical trials are described. Speculation on new paradigms, treatment goals and outcome measures aimed at improving the landscape of MS treatment is presented. Multiple disease, drug and patient-related factors should be taken into consideration when selecting the appropriate drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS.

Cultivating the Multiple Sclerosis Workforce of the Future.

PubMed

DeLuca, Gabriele C; Buckle, Guy; Cortese, Irene; Graves, Jennifer S; Halper, June; Newsome, Scott D; Sicotte, Nancy; Ford, Corey C

2017-01-01

Multiple sclerosis (MS) is a complex neurologic disorder that affects people with ever-changing needs. The MS health-care field has entered an era of exponential knowledge growth in which better understanding of the immunologic dysregulation of the disease has translated into an expanding array of treatment options. It is estimated that, if it has not already, within the next decade the demands of a growing MS patient population will outstrip the number of professionals dedicated to the management of this chronic, lifelong disease. Therefore, there is a pressing need to attract and retain clinicians in this dynamic field. In response to this need, the Foundation of the Consortium of Multiple Sclerosis Centers organized a 2-day colloquium, a Mentorship Forum, on January 23-24, 2015, bringing together talented internal medicine and neurology trainees from across North America with an interest in MS and neuroimmunology. This article highlights the rationale for the MS Mentorship Forum, its structure and content, and its outcomes. We believe that the stage has been set to interest young, promising clinicians in learning more about MS and to encourage them to consider a career in this field. In so doing, we hope to contribute to the development of the next generation of MS experts to make a palpable difference in the lives of those affected by MS.

Economic burden of multiple sclerosis and the role of managed sare organizations in multiple sclerosis management.

PubMed

Owens, Gary M

2016-06-01

Multiple sclerosis (MS) is disease that has an early age of onset and may intensify and subside with disease relapses or exacerbations interrupted by periods of stability. Because of this, patients, their families and caregivers, employers, and the entire healthcare system carry substantial clinical and economic burdens associated with the disease over of a period of many years. Although most patients with MS are covered by health insurance, the management landscape has become increasingly complex over the past decade with the introduction and approval of several new disease-modifying therapies that, while remarkably effective and well tolerated, usually come with a very high cost. Whereas the main goal of treating patients with MS is to prevent disease progression and disability, healthcare and benefit providers are faced with an ever-tipping balance point between effectively managing the disease and maximizing the value of high-cost disease-modifying therapies in an already overburdened healthcare system. Treatment of MS should be individualized, and shared decision making between patients and healthcare providers must be preserved. Healthcare providers and payers need to collaborate to ensure that resources are used optimally and not wasted, reducing both the clinical and economic burdens related to this complex chronic disorder.

Oral disease-modifying therapies for multiple sclerosis in the Middle Eastern and North African (MENA) region: an overview.

PubMed

Deleu, Dirk; Mesraoua, Boulenouar; Canibaño, Beatriz; Melikyan, Gayane; Al Hail, Hassan; El-Sheikh, Lubna; Ali, Musab; Al Hussein, Hassan; Ibrahim, Faiza; Hanssens, Yolande

2018-06-18

The introduction of new disease-modifying therapies (DMTs) for remitting-relapsing multiple sclerosis (RRMS) has considerably transformed the landscape of therapeutic opportunities for this chronic disabling disease. Unlike injectable drugs, oral DMTs promote patient satisfaction and increase therapeutic adherence. This article reviews the salient features about the mode of action, efficacy, safety, and tolerability profile of approved oral DMTs in RRMS, and reviews their place in clinical algorithms in the Middle East and North Africa (MENA) region. A systematic review was conducted using a comprehensive search of MEDLINE, PubMed, Cochrane Database of Systematic Reviews (period January 1, 1995-January 31, 2018). Additional searches of the American Academy of Neurology and European Committee for Treatment and Research in Multiple Sclerosis abstracts from 2012-2017 were performed, in addition to searches of the Food and Drug Administration and European Medicines Agency websites, to obtain relevant safety information on these DMTs. Four oral DMTs: fingolimod, teriflunomide, dimethyl fumarate, and cladribine have been approved by the regulatory agencies. Based on the number needed to treat (NNT), the potential role of these DMTs in the management of active and highly active or rapidly evolving RRMS is assessed. Finally, the place of the oral DMTs in clinical algorithms in the MENA region is reviewed.

Cerebrospinal Fluid Cytokine Expression Profile in Multiple Sclerosis and Chronic Inflammatory Demyelinating Polyneuropathy.

PubMed

Bonin, Serena; Zanotta, Nunzia; Sartori, Arianna; Bratina, Alessio; Manganotti, Paolo; Trevisan, Giusto; Comar, Manola

2018-02-01

Cerebrospinal fluid (CSF) analysis in patients with particular neurologic disorders is a powerful tool to evaluate specific central nervous system inflammatory markers for diagnostic needs, because CSF represents the specific immune micro-environment to the central nervous system. CSF samples from 49 patients with multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy (CIDP), and non-inflammatory neurologic disorders (NIND) as controls were submitted to protein expression profiles of 47 inflammatory biomarkers by multiplex Luminex bead assay to investigate possible differences in the inflammatory process for MS and CIDP. Our results showed differences in CSF cytokine levels in MS and CIDP; in particular, IL12 (p40) was significantly highly expressed in MS in comparison with CIDP and NIND, while SDF-1α and SCGF-β were significantly highly expressed in CIDP cohort when compared to MS and NIND. IL-9, IL-13, and IL-17 had higher expression levels in NIND if compared with the other groups. Our study showed that, despite some common pathogenic mechanisms, central and peripheral nervous system demyelinating diseases, such as MS and CIDP, differ in some specific inflammatory soluble proteins in CSF, underlining differences in the immune response involved in those autoimmune diseases.

Untargeted Plasma Metabolomics Identifies Endogenous Metabolite with Drug-like Properties in Chronic Animal Model of Multiple Sclerosis*

PubMed Central

Poisson, Laila M.; Suhail, Hamid; Singh, Jaspreet; Datta, Indrani; Denic, Aleksandar; Labuzek, Krzysztof; Hoda, Md Nasrul; Shankar, Ashray; Kumar, Ashok; Cerghet, Mirela; Elias, Stanton; Mohney, Robert P.; Rodriguez, Moses; Rattan, Ramandeep; Mangalam, Ashutosh K.; Giri, Shailendra

2015-01-01

We performed untargeted metabolomics in plasma of B6 mice with experimental autoimmune encephalitis (EAE) at the chronic phase of the disease in search of an altered metabolic pathway(s). Of 324 metabolites measured, 100 metabolites that mapped to various pathways (mainly lipids) linked to mitochondrial function, inflammation, and membrane stability were observed to be significantly altered between EAE and control (p < 0.05, false discovery rate <0.10). Bioinformatics analysis revealed six metabolic pathways being impacted and altered in EAE, including α-linolenic acid and linoleic acid metabolism (PUFA). The metabolites of PUFAs, including ω-3 and ω-6 fatty acids, are commonly decreased in mouse models of multiple sclerosis (MS) and in patients with MS. Daily oral administration of resolvin D1, a downstream metabolite of ω-3, decreased disease progression by suppressing autoreactive T cells and inducing an M2 phenotype of monocytes/macrophages and resident brain microglial cells. This study provides a proof of principle for the application of metabolomics to identify an endogenous metabolite(s) possessing drug-like properties, which is assessed for therapy in preclinical mouse models of MS. PMID:26546682

A Comparison of Neuroimaging Abnormalities in Multiple Sclerosis, Major Depression and Chronic Fatigue Syndrome (Myalgic Encephalomyelitis): is There a Common Cause?

PubMed

Morris, Gerwyn; Berk, Michael; Puri, Basant K

2018-04-01

There is copious evidence of abnormalities in resting-state functional network connectivity states, grey and white matter pathology and impaired cerebral perfusion in patients afforded a diagnosis of multiple sclerosis, major depression or chronic fatigue syndrome (CFS) (myalgic encephalomyelitis). Systemic inflammation may well be a major element explaining such findings. Inter-patient and inter-illness variations in neuroimaging findings may arise at least in part from regional genetic, epigenetic and environmental variations in the functions of microglia and astrocytes. Regional differences in neuronal resistance to oxidative and inflammatory insults and in the performance of antioxidant defences in the central nervous system may also play a role. Importantly, replicated experimental findings suggest that the use of high-resolution SPECT imaging may have the capacity to differentiate patients afforded a diagnosis of CFS from those with a diagnosis of depression. Further research involving this form of neuroimaging appears warranted in an attempt to overcome the problem of aetiologically heterogeneous cohorts which probably explain conflicting findings produced by investigative teams active in this field. However, the ionising radiation and relative lack of sensitivity involved probably preclude its use as a routine diagnostic tool.

Multiple Sclerosis and Obesity: Possible Roles of Adipokines

PubMed Central

Guerrero-García, José de Jesús; Márquez-Aguirre, Ana Laura

2016-01-01

Multiple Sclerosis (MS) is an autoimmune disorder of the Central Nervous System that has been associated with several environmental factors, such as diet and obesity. The possible link between MS and obesity has become more interesting in recent years since the discovery of the remarkable properties of adipose tissue. Once MS is initiated, obesity can contribute to increased disease severity by negatively influencing disease progress and treatment response, but, also, obesity in early life is highly relevant as a susceptibility factor and causally related risk for late MS development. The aim of this review was to discuss recent evidence about the link between obesity, as a chronic inflammatory state, and the pathogenesis of MS as a chronic autoimmune and inflammatory disease. First, we describe the main cells involved in MS pathogenesis, both from neural tissue and from the immune system, and including a new participant, the adipocyte, focusing on their roles in MS. Second, we concentrate on the role of several adipokines that are able to participate in the mediation of the immune response in MS and on the possible cross talk between the latter. Finally, we explore recent therapy that involves the transplantation of adipocyte precursor cells for the treatment of MS. PMID:27721574

Improvements in cognition, quality of life, and physical performance with clinical Pilates in multiple sclerosis: a randomized controlled trial

PubMed Central

Küçük, Fadime; Kara, Bilge; Poyraz, Esra Çoşkuner; İdiman, Egemen

2016-01-01

[Purpose] The aim of this study was to determine the effects of clinical Pilates in multiple sclerosis patients. [Subjects and Methods] Twenty multiple sclerosis patients were enrolled in this study. The participants were divided into two groups as the clinical Pilates and control groups. Cognition (Multiple Sclerosis Functional Composite), balance (Berg Balance Scale), physical performance (timed performance tests, Timed up and go test), tiredness (Modified Fatigue Impact scale), depression (Beck Depression Inventory), and quality of life (Multiple Sclerosis International Quality of Life Questionnaire) were measured before and after treatment in all participants. [Results] There were statistically significant differences in balance, timed performance, tiredness and Multiple Sclerosis Functional Composite tests between before and after treatment in the clinical Pilates group. We also found significant differences in timed performance tests, the Timed up and go test and the Multiple Sclerosis Functional Composite between before and after treatment in the control group. According to the difference analyses, there were significant differences in Multiple Sclerosis Functional Composite and Multiple Sclerosis International Quality of Life Questionnaire scores between the two groups in favor of the clinical Pilates group. There were statistically significant clinical differences in favor of the clinical Pilates group in comparison of measurements between the groups. Clinical Pilates improved cognitive functions and quality of life compared with traditional exercise. [Conclusion] In Multiple Sclerosis treatment, clinical Pilates should be used as a holistic approach by physical therapists. PMID:27134355

Improvements in cognition, quality of life, and physical performance with clinical Pilates in multiple sclerosis: a randomized controlled trial.

PubMed

Küçük, Fadime; Kara, Bilge; Poyraz, Esra Çoşkuner; İdiman, Egemen

2016-03-01

[Purpose] The aim of this study was to determine the effects of clinical Pilates in multiple sclerosis patients. [Subjects and Methods] Twenty multiple sclerosis patients were enrolled in this study. The participants were divided into two groups as the clinical Pilates and control groups. Cognition (Multiple Sclerosis Functional Composite), balance (Berg Balance Scale), physical performance (timed performance tests, Timed up and go test), tiredness (Modified Fatigue Impact scale), depression (Beck Depression Inventory), and quality of life (Multiple Sclerosis International Quality of Life Questionnaire) were measured before and after treatment in all participants. [Results] There were statistically significant differences in balance, timed performance, tiredness and Multiple Sclerosis Functional Composite tests between before and after treatment in the clinical Pilates group. We also found significant differences in timed performance tests, the Timed up and go test and the Multiple Sclerosis Functional Composite between before and after treatment in the control group. According to the difference analyses, there were significant differences in Multiple Sclerosis Functional Composite and Multiple Sclerosis International Quality of Life Questionnaire scores between the two groups in favor of the clinical Pilates group. There were statistically significant clinical differences in favor of the clinical Pilates group in comparison of measurements between the groups. Clinical Pilates improved cognitive functions and quality of life compared with traditional exercise. [Conclusion] In Multiple Sclerosis treatment, clinical Pilates should be used as a holistic approach by physical therapists.

Diagnostic evaluation of dysphagia in multiple sclerosis patients using a Persian version of DYMUS questionnaire.

PubMed

Pajouh, Sahar Danesh; Moradi, Negin; Shaterzadeh Yazdi, Mohammad Jafar; Latifi, Seyed Mahmoud; Mehravar, Mohammad; Majdinasab, Nastaran; Olapour, Ali Reza; Soltani, Majid; Khanchezar, Fatemeh

2017-10-01

Multiple sclerosis is a chronic neurological disease that may cause swallowing disorders. Dysphagia is a common problem, which patients with different levels of disability may encounter, but it is usually underestimated; therefore, effective assessments need to be performed before any serious complications. The aim of this study was to identify the frequency and characteristics of dysphagia in multiple sclerosis patients of Khuzestan MS society, using a Persian version of Dysphagia in Multiple Sclerosis (DYMUS) questionnaire. 105 consecutive MS patients (84 F and 21 M, mean age 33.8 ± 8.5 years, mean disease duration 3.5 ± 3.1 years, mean Expanded Disability Status Scale (EDSS) 1.8 ± 1.3) participated in the study and the DYMUS questionnaire was administered by a trained speech therapist. The results have shown that 55 MS patients (52.4%) had dysphagia and the dysphagia was significantly associated with the disease course of MS (p = 0.02). However, significant associations between DYMUS values and EDSS, disease duration, age, and gender were not observed. (Respectively, p = 0.4, p = 0.09, p = 0.1, p = 1.0). In the dysphagia group, based on dysphagia severity, 17.1% and 35.2% of patients had mild and alarming dysphagia, respectively. Although, the patients with alarming dysphagia had longer disease duration, higher EDSS score and more with SP, PP and PR disease course than the patients with mild dysphagia, these differences were not significant. The oropharyngeal dysphagia in MS patients is very common even in early stages of the disease; therefore, it is important to assess these patients carefully and to initiate a treatment program if needed. Copyright © 2017 Elsevier B.V. All rights reserved.

[The overall assessment of psychological well - being of patients with multiple sclerosis after the application of physical therapy. Part 2].

PubMed

Kubsik-Gidlewska, Anna; Klimkiewicz, Robert; Klimkiewicz, Paulina; Janczewska, Katarzyna; Jankowska, Agnieszka; Nowakowski, Tomasz; Woldańska-Okońska, Marta

2017-01-01

Multiple sclerosis is a chronic demyelinating disease of the central nervous system, which results a progressive disability. The disease reduces the quality of life of patients, changes the general health perceptions, and also limits performing social roles because of emotional problems. Evaluation of the impact of the methods of rehabilitation to improve the mental health of patients with multiple sclerosis, and also to change individual parameters included in the overall assessment of mental health. The study was conducted in 2010-2014 at the Department of Physical Medicine and Rehabilitation in Lodz. The study included 120 patients with multiple sclerosis. Patients were classified into 4 test groups: in the first was used the laser, in the second - laser and magnetostimulation, in the third - kinesiotherapy, and in the fourth - magnetostimulation. The tests were carried out three times. To evaluate the quality of life was used Quality of Life Questionnaire (MSQOL-54), analyzed the overall assessment of mental health. The improvement in a range of parameters, an overall assessment of the quality of mental health has allowed to get a better overall psychological well-being. ,There was oserved a statistically significant difference at the level of p<0.001 between groups in 4/5 investigated parameters, statistically significant differences weren't obserwed at the evaluation of cognitive functions. The greatest improvement was observed in Group II and Group IV. In the examination it was confirmed an effectiveness of physical treatment, such a the laser radiation and magnetostimulation. Synergism of both methods in their biological activity, allows for evoke of hysteresis fenomenon, resulting in the maintenance of the treatment effects after cessation of rehabilitation. Applying the classical kinesiotherapy only doesn't allow to get long-term effects.

The Relational Impact of Multiple Sclerosis: An Integrative Review of the Literature Using a Cognitive Analytic Framework.

PubMed

Blundell Jones, Joanna; Walsh, Sue; Isaac, Claire

2017-12-01

This integrative literature review uses cognitive analytic therapy (CAT) theory to examine the impact of a chronic illness, multiple sclerosis (MS), on relationships and mental health. Electronic searches were conducted in six medical and social science databases. Thirty-eight articles met inclusion criteria, and also satisfied quality criteria. Articles revealed that MS-related demands change care needs and alter relationships. Using a CAT framework, the MS literature was analysed, and five key patterns of relating to oneself and to others were identified. A diagrammatic formulation is proposed that interconnects these patterns with wellbeing and suggests potential "exits" to improve mental health, for example, assisting families to minimise overprotection. Application of CAT analysis to the literature clarifies relational processes that may affect mental health among individuals with MS, which hopefully will inform how services assist in reducing unhelpful patterns and improve coping. Further investigation of the identified patterns is needed.

Uses of Complementary and Alternative Medicine in Multiple Sclerosis

PubMed Central

Namjooyan, Foroogh; Ghanavati, Rahil; Majdinasab, Nastaran; Jokari, Shiva; Janbozorgi, Mohammad

2014-01-01

Multiple sclerosis (MS) is a chronic, disabling, recurrent demyelination of the central nervous system (CNS). It could affect different regions in the brain and spinal cord, and according to the domain which is affected, it could cause different symptoms such as motor, sensory, or visual impairment; fatigue; bowel, bladder, and sexual dysfunction; cognitive impairment; and depression. MS patients also face reduced quality of life. Drugs that are used in MS are not fully efficient and patients suffer from many symptoms and adverse effects. Today there is an increasing trend of using complementary and alternative medicine (CAM). People are more likely to use this type of treatment. Using appropriate lifestyle and CAM therapy can subside some of the symptoms and could improve the quality of life in these patients. Many people with MS explore CAM therapies for their symptoms. This review is aimed to introduce CAM therapies that could be used in MS patients. PMID:25161918

Second-Generation Non-Covalent NAAA Inhibitors are Protective in a Model of Multiple Sclerosis.

PubMed

Migliore, Marco; Pontis, Silvia; Fuentes de Arriba, Angel Luis; Realini, Natalia; Torrente, Esther; Armirotti, Andrea; Romeo, Elisa; Di Martino, Simona; Russo, Debora; Pizzirani, Daniela; Summa, Maria; Lanfranco, Massimiliano; Ottonello, Giuliana; Busquet, Perrine; Jung, Kwang-Mook; Garcia-Guzman, Miguel; Heim, Roger; Scarpelli, Rita; Piomelli, Daniele

2016-09-05

Palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are endogenous lipid mediators that suppress inflammation. Their actions are terminated by the intracellular cysteine amidase, N-acylethanolamine acid amidase (NAAA). Even though NAAA may offer a new target for anti-inflammatory therapy, the lipid-like structures and reactive warheads of current NAAA inhibitors limit the use of these agents as oral drugs. A series of novel benzothiazole-piperazine derivatives that inhibit NAAA in a potent and selective manner by a non-covalent mechanism are described. A prototype member of this class (8) displays high oral bioavailability, access to the central nervous system (CNS), and strong activity in a mouse model of multiple sclerosis (MS). This compound exemplifies a second generation of non-covalent NAAA inhibitors that may be useful in the treatment of MS and other chronic CNS disorders. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The interaction of fatigue, physical activity, and health-related quality of life in adults with multiple sclerosis (MS) and cardiovascular disease (CVD).

PubMed

Newland, Pamela K; Lunsford, Valerie; Flach, Alicia

2017-02-01

In addition to the underlying health problems and disability associated with multiple sclerosis (MS) and cardiovascular disease (CVD), adults with each of these chronic illnesses are independently known to experience fatigue. While fatigue's influence on physical activity and health related quality of life (HRQOL) with each of these illnesses has been discussed, what is lacking is information on how fatigue impacts physical activity and health related quality of life, and ultimately self-management for adults with these conditions. Additionally, individuals may be unaware of the significance of maintaining optimal physical activity in order to maintain everyday function and self-management. Thus, the purpose of this article is to discuss the complex effect of fatigue on physical activity and HRQOL among adults with MS and CVD, and to present potential self-management strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

Plasma exchange therapy in steroid-unresponsive relapses in patients with multiple sclerosis.

PubMed

Trebst, Corinna; Reising, Ansgar; Kielstein, Jan T; Hafer, Carsten; Stangel, Martin

2009-01-01

Plasma exchange (PE) is well established for conditions such as rapid progressive vasculitis associated with autoantibodies against neutrophil cytoplasmic antigens (ANCA), anti-glomerular basement membrane (GBM) antibody disease, or thrombotic thrombocytopenic purpura (TTP). Also, several neurological disorders, such as acute worsening in myasthenia gravis, Guillan-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP), can successfully be treated with PE. Only small case series have previously shown that PE is also effective in relapses in patients with multiple sclerosis (MS). We report our experiences of PE therapy in a series of 20 patients with 21 steroid unresponsive MS relapses. A marked-to-moderate clinical response with clear gain of function in 76% of patients with uni- or bilateral optic neuritis and in 87.5% of patients with relapses other than optic neuritis was observed. PE is an effective and well tolerated therapeutic option for steroid-unresponsive MS relapses.

Multiple sclerosis: geoepidemiology, genetics and the environment.

PubMed

Milo, Ron; Kahana, Esther

2010-03-01

Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system characterized by relapses and remissions. The risk of acquiring this complex disease is associated with exposure to environmental factors in genetically susceptible individuals. The epidemiology of MS has been extensively studied. We review the geographic epidemiology of the disease, the influence of immigration, age at immigration, clustering and epidemics. Various presumptive risk factors are discussed such as ultraviolet radiation, vitamin D, Epstein-Barr virus and infectious mononucleosis, other infectious agents and non-infectious factors. Two different hypotheses, the hygiene hypothesis and the prevalence hypothesis, were proposed to explain these environmental risk factors for MS. The epidemiological data, combined with pathological and immunological data, may contribute to the debate whether MS is an autoimmune disease, a latent or persistent viral disease, or a neurodegenerative disease. 2009 Elsevier B.V. All rights reserved.

Vogt Koyanagi Harada Syndrome mimicking multiple sclerosis: A case report and review of the literature.

PubMed

Algahtani, Hussein; Shirah, Bader; Algahtani, Raghad; Alkahtani, Abdulah; Alwadie, Saeed

2017-02-01

Vogt Koyanagi Harada (VKH) Syndrome, also called uveomeningioencephalitis, is a chronic disorder characterized by inflammation of the uvea, meninges, auditory system, and integumentary system. The association between VKH syndrome and multiple sclerosis (MS) has been reported only once in the literature in a patient who developed VKH syndrome after two years of the diagnosis of MS. In this article, we report a case who was misdiagnosed and treated as MS until she was proven to have VKH syndrome, and a diagnosis of MS was excluded. VKH syndrome is a systemic disorder that may present with clinical and/or radiological features mimicking MS. Applying diagnostic criteria is extremely important for confirming or excluding the diagnosis. Detailed history and physical examination are of paramount importance to score the final diagnosis. Rigorous search for red flags for both conditions is very helpful. Copyright © 2017 Elsevier B.V. All rights reserved.

Multiple sclerosis

MedlinePlus

... this page: //medlineplus.gov/ency/article/000737.htm Multiple sclerosis To use the sharing features on this page, please enable JavaScript. Multiple sclerosis (MS) is an autoimmune disease that affects the ...

Use of the 2010 McDonald criteria can facilitate early diagnosis of pediatric multiple sclerosis in a predominantly black cohort.

PubMed

Williams, Mitchel T; Tapos, Daniela O; Juhász, Csaba

2014-12-01

Pediatric-onset multiple sclerosis represents around 3-5% of all patients with multiple sclerosis. Both the 2005 and 2010 McDonald criteria for multiple sclerosis have been suggested for the possible use in pediatric-onset multiple sclerosis. Modifications incorporated into the 2010 criteria enabled the fulfillment of dissemination in time to be met with the initial magnetic resonance imaging. The present study was designed to compare the diagnostic sensitivity of these criteria at initial presentation, the time to fulfilling them, and secondary effects of ethnicity in pediatric-onset multiple sclerosis. Twenty-five children with clinically definite multiple sclerosis (mean age, 14.6 ± 3.1 years; 15 girls) from a single center between 2005 and 2012 were analyzed using both the 2005 and 2010 McDonald criteria based on initial clinical presentation and neuroimaging findings comparing diagnostic sensitivity, time interval to meet diagnosis, and ethnicity. Initial multiple sclerosis diagnosis rates applying the 2005 McDonald criteria were 32% compared with 92% for the 2010 criteria (P = 0.0003). The mean time after initial signs until the 2005 and 2010 McDonald criteria for multiple sclerosis were met was 5.0 vs 0.7 months, respectively (P = 0.001). Time to diagnosis using the 2010 criteria was shorter in black children than the European white (P = 0.005). The 2010 McDonald criteria are an appropriate tool for the timely diagnosis of pediatric multiple sclerosis, especially in black children, potentially allowing an earlier initiation of disease-modifying therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Is impaired cerebral vasoreactivity an early marker of cognitive decline in multiple sclerosis patients?

PubMed

Metzger, Aude; Le Bars, Emmanuelle; Deverdun, Jeremy; Molino, François; Maréchal, Bénédicte; Picot, Marie-Christine; Ayrignac, Xavier; Carra, Clarisse; Bauchet, Luc; Krainik, Alexandre; Labauge, Pierre; Menjot de Champfleur, Nicolas

2018-03-01

The link between cerebral vasoreactivity and cognitive status in multiple sclerosis remains unclear. The aim of the present study was to investigate a potential decrease of cerebral vasoreactivity in multiple sclerosis patients and correlate it with cognitive status. Thirty-three patients with multiple sclerosis (nine progressive and 24 remitting forms, median age: 39 years, 12 males) and 22 controls underwent MRI with a hypercapnic challenge to assess cerebral vasoreactivity and a neuropsychological assessment. Cerebral vasoreactivity, measured as the cerebral blood flow percent increase normalised by end-tidal carbon dioxide variation, was assessed globally and by regions of interest using the blood oxygen level-dependent technique. Non-parametric statistics tests were used to assess differences between groups, and associations were estimated using linear models. Cerebral vasoreactivity was lower in patients with cognitive impairment than in cognitively normal patients (p=0.004) and was associated with education level in patients (R 2 = 0.35; p = 0.047). There was no decrease in cerebral vasoreactivity between patients and controls. Cognitive impairment in multiple sclerosis may be mediated through decreased cerebral vasoreactivity. Cerebral vasoreactivity could therefore be considered as a marker of cognitive decline in multiple sclerosis. • Cerebral vasoreactivity does not differ between multiple sclerosis patients and controls. • Cerebral vasoreactivity measure is linked to cognitive impairment in multiple sclerosis. • Cerebral vasoreactivity is linked to level of education in multiple sclerosis.

Multiple sclerosis in children: an update on clinical diagnosis, therapeutic strategies, and research

PubMed Central

Waldman, Amy; Ghezzi, Angelo; Bar-Or, Amit; Mikaeloff, Yann; Tardieu, Marc; Banwell, Brenda

2015-01-01

The clinical features, diagnostic challenges, neuroimaging appearance, therapeutic options, and pathobiological research progress in childhood—and adolescent—onset multiple sclerosis have been informed by many new insights in the past 7 years. National programmes in several countries, collaborative research efforts, and an established international paediatric multiple sclerosis study group have contributed to revised clinical diagnostic definitions, identified clinical features of multiple sclerosis that differ by age of onset, and made recommendations regarding the treatment of paediatric multiple sclerosis. The relative risks conveyed by genetic and environmental factors to paediatric multiple sclerosis have been the subject of several large cohort studies. MRI features have been characterised in terms of qualitative descriptions of lesion distribution and applicability of MRI aspects to multiple sclerosis diagnostic criteria, and quantitative studies have assessed total lesion burden and the effect of the disease on global and regional brain volume. Humoral-based and cell-based assays have identified antibodies against myelin, potassium-channel proteins, and T-cell profiles that support an adult-like T-cell repertoire and cellular reactivity against myelin in paediatric patients with multiple sclerosis. Finally, the safety and efficacy of standard first-line therapies in paediatric multiple sclerosis populations are now appreciated in more detail, and consensus views on the future conduct and feasibility of phase 3 trials for new drugs have been proposed. PMID:25142460

Feasibility of mesenchymal stem cell culture expansion for a phase I clinical trial in multiple sclerosis.

PubMed

Planchon, Sarah M; Lingas, Karen T; Reese Koç, Jane; Hooper, Brittney M; Maitra, Basabi; Fox, Robert M; Imrey, Peter B; Drake, Kylie M; Aldred, Micheala A; Lazarus, Hillard M; Cohen, Jeffrey A

2018-01-01

Multiple sclerosis is an inflammatory, neurodegenerative disease of the central nervous system for which therapeutic mesenchymal stem cell transplantation is under study. Published experience of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical trials is limited. To determine the feasibility of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical use. In a phase I trial, autologous, bone marrow-derived mesenchymal stem cells were isolated from 25 trial participants with multiple sclerosis and eight matched controls, and culture-expanded to a target single dose of 1-2 × 10 6 cells/kg. Viability, cell product identity and sterility were assessed prior to infusion. Cytogenetic stability was assessed by single nucleotide polymorphism analysis of mesenchymal stem cells from 18 multiple sclerosis patients and five controls. One patient failed screening. Mesenchymal stem cell culture expansion was successful for 24 of 25 multiple sclerosis patients and six of eight controls. The target dose was achieved in 16-62 days, requiring two to three cell passages. Growth rate and culture success did not correlate with demographic or multiple sclerosis disease characteristics. Cytogenetic studies identified changes on one chromosome of one control (4.3%) after extended time in culture. Culture expansion of mesenchymal stem cells from multiple sclerosis patients as donors is feasible. However, culture time should be minimized for cell products designated for therapeutic administration.

Impact of multiple sclerosis on employment and use of job-retention strategies: The situation in France in 2015.

PubMed

Fantoni-Quinton, Sophie; Kwiatkowski, Arnaud; Vermersch, Patrick; Roux, Bastien; Hautecoeur, Patrick; Leroyer, Ariane

2016-06-13

The main objective of this survey of persons with multiple sclerosis was to describe their employment situation. Secondary objectives were to ascertain when and how multiple sclerosis symptoms first impact employment per se and what strategies persons with multiple sclerosis use to cope with their employment problems. A retrospective survey was conducted to collect data from persons with multiple sclerosis aged 18 years and over, using a computer-assisted web tool. A total of 941 respondents were working at the time of multiple sclerosis diagnosis or had worked subsequently. Median time since diagnosis was 10 years. Multiple sclerosis had an impact on employment for 74.3% of respondents. The overall employment rate at the time of the survey was 68.1%; 27.2% had discontinued their occupational activity for a multiple sclerosis-related reason. Median time from diagnosis to multiple sclerosis-related cessation of occupational activity was 24.0 years (95% confidence interval (CI) 21.7-26.3 years). Respondents were poorly aware of available tools designed to assist them in retaining employment. This study highlights the importance of early intervention by the occupational medicine physician in order to favour job retention and use of available tools by all workers with MS and not only those with a recognized status as a disabled worker.

In Vivo Imaging of Cortical Inflammation and Subpial Pathology in Multiple Sclerosis by Combined PET and MRI

DTIC Science & Technology

2014-09-01

and Subpial Pathology in Multiple Sclerosis by Combined PET and MRI PRINCIPAL INVESTIGATOR: Dr. Caterina Mainero...studies in multiple sclerosis (MS) suggested that cortical demyelinating lesions, which are hardly detected in vivo on conventional magnetic resonance...disease progression in many MS cases. 15. SUBJECT TERMS Multiple sclerosis ; cortex; cortical sulci; neuroinflammation; microglia; cortical

Infectious mononucleosis-linked HLA class I single nucleotide polymorphism is associated with multiple sclerosis.

PubMed

Jafari, Naghmeh; Broer, Linda; Hoppenbrouwers, Ilse A; van Duijn, Cornelia M; Hintzen, Rogier Q

2010-11-01

Multiple sclerosis is a presumed autoimmune disease associated with genetic and environmental risk factors such as infectious mononucleosis. Recent research has shown infectious mononucleosis to be associated with a specific HLA class I polymorphism. Our aim was to test if the infectious mononucleosis-linked HLA class I single nucleotide polymorphism (rs6457110) is also associated with multiple sclerosis. Genotyping of the HLA-A single nucleotide polymorphism rs6457110 using TaqMan was performed in 591 multiple sclerosis cases and 600 controls. The association of multiple sclerosis with the HLA-A single nucleotide polymorphism was tested using logistic regression adjusted for age, sex and HLA-DRB1*1501. HLA-A minor allele (A) is associated with multiple sclerosis (OR = 0.68; p = 4.08 × 10( -5)). After stratification for HLA-DRB1*1501 risk allele (T) carrier we showed a significant OR of 0.70 (p = 0.003) for HLA-A. HLA class I single nucleotide polymorphism rs6457110 is associated with infectious mononucleosis and multiple sclerosis, independent of the major class II allele, supporting the hypothesis that shared genetics may contribute to the association between infectious mononucleosis and multiple sclerosis.

Neurotoxicity

MedlinePlus

... disorders such as Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and dementia. Also being studied are the mechanisms ... disorders such as Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and dementia. Also being studied are the mechanisms ...

Spasticity

MedlinePlus

... in association with spinal cord injury, multiple sclerosis, cerebral palsy, stroke, brain or head trauma, amyotrophic lateral sclerosis, ... in association with spinal cord injury, multiple sclerosis, cerebral palsy, stroke, brain or head trauma, amyotrophic lateral sclerosis, ...

Investigation of human multiple sclerosis lesions using high resolution spectrally unmixed CARS microscopy

NASA Astrophysics Data System (ADS)

Poon, Kelvin W.; Brideau, Craig; Teo, Wulin; Schenk, Geert J.; Klaver, Roel; Klauser, Antoine M.; Kawasoe, Jean H.; Geurts, Jeroen J. G.; Stys, Peter K.

2013-03-01

The pathology of multiple sclerosis (MS) involves both the gray and white matter regions of the brain and spinal cord. It is characterized by various combinations of demyelination, inflammatory infiltration, axonal degeneration, and later gliosis in chronic lesions. While acute and chronic white matter plaques are well characterized and easily identified, evidence indicates that the CNS of MS patients may be globally altered, with subtle abnormalities found in grossly normal appearing white matter (NAWM) and in diffusely abnormal white matter (DAWM) where histochemical stains and advanced magnetic resonance imaging indicate altered tissue composition. Thus, the prototypical acute inflammatory lesion may merely represent the most obvious manifestation of a chronic widespread involvement of the CNS, which is difficult to examine reliably. The current study deals with the microstructure and biochemistry of demyelination, remyelination and axonal loss in various regions of post-mortem human MS brain, including NAWM, areas of remyelination and more typical acute and chronic lesions. The myelin sheath, neuroglia and perivascular spaces were investigated using a novel Coherent Anti-Stokes Raman Scattering (CARS) microscope with simultaneous Two-Photon Excited Fluorescence (TPEF) imaging. The active CH stretching region between 2800 and 3000 cm-1 was probed to provide chemically specific, high resolution, label-free imaging pertaining to the progression of the disease. CARS data were correlated with TPEF and conventional histochemical and immunohistochemical stains. Our novel CARS microscopy system provides detailed morphological and biochemical information regarding CNS pathology in MS and that may be applicable to a broad range of other human brain and spinal cord disorders.

Progression of regional grey matter atrophy in multiple sclerosis

PubMed Central

Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

2018-01-01

Abstract See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article. Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple sclerosis and late atrophy in primary-progressive multiple sclerosis. Patients with secondary-progressive multiple sclerosis showed the highest event-based model stage (the highest number of atrophic regions, P < 0.001) at the study entry. All multiple sclerosis phenotypes, but clinically isolated syndrome, showed a faster rate of increase in the event-based model stage than healthy controls. T2 lesion load and disease duration in all patients were associated with increased event-based model stage, but no effects of disease-modifying treatments and comorbidity on event-based model stage were observed. The annualized rate of event-based model stage was associated with the disability accumulation in relapsing-remitting multiple sclerosis, independent of disease duration (P < 0.0001). The data-driven staging of atrophy progression in a large multiple sclerosis sample demonstrates that grey matter atrophy spreads to involve more regions over time. The sequence in which regions become atrophic is reasonably consistent across multiple sclerosis phenotypes. The spread of atrophy was associated with disease duration and with disability accumulation over time in relapsing-remitting multiple sclerosis. PMID:29741648

Progression of regional grey matter atrophy in multiple sclerosis.

PubMed

Eshaghi, Arman; Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Prados, Ferran; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

2018-06-01

See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article.Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple sclerosis and late atrophy in primary-progressive multiple sclerosis. Patients with secondary-progressive multiple sclerosis showed the highest event-based model stage (the highest number of atrophic regions, P < 0.001) at the study entry. All multiple sclerosis phenotypes, but clinically isolated syndrome, showed a faster rate of increase in the event-based model stage than healthy controls. T2 lesion load and disease duration in all patients were associated with increased event-based model stage, but no effects of disease-modifying treatments and comorbidity on event-based model stage were observed. The annualized rate of event-based model stage was associated with the disability accumulation in relapsing-remitting multiple sclerosis, independent of disease duration (P < 0.0001). The data-driven staging of atrophy progression in a large multiple sclerosis sample demonstrates that grey matter atrophy spreads to involve more regions over time. The sequence in which regions become atrophic is reasonably consistent across multiple sclerosis phenotypes. The spread of atrophy was associated with disease duration and with disability accumulation over time in relapsing-remitting multiple sclerosis.

Characteristics and correlates of coping with multiple sclerosis: a systematic review.

PubMed

Keramat Kar, Maryam; Whitehead, Lisa; Smith, Catherine M

2017-10-10

The purpose of this systematic review was to examine coping strategies that people with multiple sclerosis use, and to identify factors that influence their coping pattern. This systematic review followed the Joanna Briggs Institute guidelines for synthesizing descriptive quantitative research. The following databases were searched from the inception of databases until December 2016: Ovid (Medline, Embase, CINAHL, and PsycINFO), Science Direct, Web of Science, and Scopus. Manual search was also conducted from the reference lists of retrieved articles. Findings related to the patterns of coping with multiple sclerosis and factors influencing coping with multiple sclerosis were extracted and synthesized. The search of the database yielded 455 articles. After excluding duplicates (n = 341) and studies that did not meet the inclusion criteria (n = 27), 71 studies were included in the full-text review. Following the full-text, a further 21 studies were excluded. Quality appraisal of 50 studies was completed, and 38 studies were included in the review. Synthesis of findings indicated that people with multiple sclerosis use emotional and avoidance coping strategies more than other types of coping, particularly in the early stages of the disease. In comparison to the general population, people with multiple sclerosis were less likely to use active coping strategies and used more avoidance and emotional coping strategies. The pattern of coping with multiple sclerosis was associated with individual, clinical and psychological factors including gender, educational level, clinical course, mood and mental status, attitude, personality traits, and religious beliefs. The findings of this review suggest that considering individual or disease-related factors could help healthcare professionals in identifying those less likely to adapt to multiple sclerosis. This information could also be used to provide client-centered rehabilitation for people living with multiple sclerosis based on their individual responses and perceptions for coping. Implications for rehabilitation Engagement in coping with multiple sclerosis has been associated with individual factors and neuropsychological functions. Considering individual and disease-related factors would allow healthcare professionals to provide more tailored interventions to maintain and master coping with multiple sclerosis. People living with multiple sclerosis should be empowered to appraise and manage ability to cope based on the contextual evidence (individual and clinical condition). Rehabilitation services should move beyond physical management incorporating behavioral aspects for better functioning in living with multiple sclerosis.

Multiple Sclerosis

MedlinePlus

Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the ... attacks healthy cells in your body by mistake. Multiple sclerosis affects women more than men. It often begins ...

Episodic Mood Changes Preceding an Exacerbation of Multiple Sclerosis

PubMed Central

Sharma, Priya; Morrow, Sarah A.; Owen, Richard J.

2015-01-01

Multiple sclerosis is a neurologic inflammatory disease that can manifest with psychiatric symptoms. Although depression is the most common psychiatric diagnosis in patients with multiple sclerosis, how depression develops is not fully understood. We present the case of an individual who displayed episodic mood changes preceding an exacerbation of multiple sclerosis symptoms. The clinical and research implications of this association are discussed. PMID:26835163

Mobilization of Neural Precursors in the Circulating Blood of Patients with Multiple Sclerosis

DTIC Science & Technology

2012-07-01

circulating blood of patients with multiple sclerosis PRINCIPAL INVESTIGATOR: Ernesto R. Bongarzone, Ph.D... multiple sclerosis 5b. GRANT NUMBER W81XWH-09-1-0427 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Ernesto R. Bongarzone...NOTES 14. ABSTRACT Relapsing remitting multiple sclerosis (RRMS) is demyelinating disease that affects both men and women and is characterized by

Physical activity and exercise priorities in community dwelling people with multiple sclerosis: a Delphi study.

PubMed

Stennett, Andrea; De Souza, Lorraine; Norris, Meriel

2018-07-01

Exercise and physical activity have been found to be beneficial in managing disabilities caused by multiple sclerosis. Despite the known benefits, many people with multiple sclerosis are inactive. This study aimed to identify the prioritised exercise and physical activity practices of people with multiple sclerosis living in the community and the reasons why they are engaged in these activities. A four Round Delphi questionnaire scoped and determined consensus of priorities for the top 10 exercise and physical activities and the reasons why people with multiple sclerosis (n = 101) are engaged in these activities. Data were analysed using content analysis, descriptive statistics, and non-parametric tests. The top 10 exercise and physical activity practices and the top 10 reasons why people with multiple sclerosis (n = 70) engaged in these activities were identified and prioritised. Consensus was achieved for the exercise and physical activities (W = 0.744, p < .0001) and for the reasons they engaged in exercise and physical activity (W = 0.723, p < .0001). The exercise and physical activity practices and the reasons people with multiple sclerosis engaged in exercise and physical activity were diverse. These self-selected activities and reasons highlighted that people with multiple sclerosis might conceptualise exercise and physical activity in ways that may not be fully appreciated or understood by health professionals. Considerations of the views of people with multiple sclerosis may be essential if the goal of increasing physical activity in this population is to be achieved. Implications for Rehabilitation Health professionals should work collaboratively with people with multiple sclerosis to understand how they prioritise activities, the underlying reasons for their prioritisations and embed these into rehabilitation programmes. Health professionals should utilise activities prioritised by people with multiple sclerosis in the community as a way to support, promote, and sustain exercise and physical activity in this population. Rehabilitation interventions should include both the activities people with multiple sclerosis prioritise and the reasons why they engage in exercise and physical activity as another option for increasing physical activity levels and reducing sedentary behaviours.

The Impact of Five VDR Polymorphisms on Multiple Sclerosis Risk and Progression: a Case-Control and Genotype-Phenotype Study.

PubMed

Křenek, Pavel; Benešová, Yvonne; Bienertová-Vašků, Julie; Vašků, Anna

2018-04-01

Vitamin D receptor polymorphisms have been the target of many studies focusing on multiple sclerosis. However, previously reported results have been inconclusive. The objective of this study was to investigate the association between five vitamin D receptor polymorphisms (EcoRV, FokI, ApaI, TaqI, and BsmI) and multiple sclerosis susceptibility and its course. The study was carried out as a case-control and genotype-phenotype study, consisted of 296 Czech multiple sclerosis patients and 135 healthy controls. Genotyping was carried out using polymerase chain reaction and restriction analysis. In multiple sclerosis men, allele and/or genotype distributions differed in EcoRV, TaqI, BsmI, and ApaI polymorphisms as compared to controls (EcoRV, p a = 0.02; Taq, p g = 0.02, p a = 0.02; BsmI, p g = 0.02, p a = 0.04; ApaI, p g = 0.008, p a = 0.005). In multiple sclerosis women, differences in the frequency of alleles and genotypes were found to be significant in ApaI (controls vs multiple sclerosis women: p g = 0.01, p a = 0.05). Conclusive results were observed between multiple sclerosis women in the case of EcoRV [differences in Expanded Disability Status Scale (p = 0.05); CT genotype was found to increase the risk of primary progressive multiple sclerosis 5.5 times (CT vs CC+TT p corr = 0.01, sensitivity 0.833, specificity 0.525, power test 0.823)] and FokI [borderline difference in Multiple Sclerosis Severity Score (p = 0.05)]. Our results indicate that the distribution of investigated vitamin D receptor polymorphisms is a risk factor for multiple sclerosis susceptibility and progression in the Czech population. The association between disease risk and polymorphisms was found to be stronger in men. The association of disease progression with polymorphisms was observed only in women.

Development and validation of a patient self-assessed questionnaire on satisfaction with communication of the multiple sclerosis diagnosis.

PubMed

Solari, A; Mattarozzi, K; Vignatelli, L; Giordano, A; Russo, P M; Uccelli, M Messmer; D'Alessandro, R

2010-10-01

We describe the development and clinical validation of a patient self-administered tool assessing the quality of multiple sclerosis diagnosis disclosure. A multiple sclerosis expert panel generated questionnaire items from the Doctor's Interpersonal Skills Questionnaire, literature review, and interviews with neurology inpatients. The resulting 19-item Comunicazione medico-paziente nella Sclerosi Multipla (COSM) was pilot tested/debriefed on seven patients with multiple sclerosis and administered to 80 patients newly diagnosed with multiple sclerosis. The resulting revised 20-item version (COSM-R) was debriefed on five patients with multiple sclerosis, field tested/debriefed on multiple sclerosis patients, and field tested on 105 patients newly diagnosed with multiple sclerosis participating in a clinical trial on an information aid. The hypothesized monofactorial structure of COSM-R section 2 was tested on the latter two groups. The questionnaire was well accepted. Scaling assumptions were satisfactory in terms of score distributions, item-total correlations and internal consistency. Factor analysis confirmed section 2's monofactorial structure, which was also test-retest reliable (intraclass correlation coefficient [ICC] 0.73; 95% CI 0.54-0.85). Section 1 had only fair test-retest reliability (ICC 0.45; 95% CI 0.12-0.69), and three items had 8-21% missed responses. COSM-R is a brief, easy-to-interpret MS-specific questionnaire for use as a health care indicator.

[Effects of nutritional status on the multiple sclerosis disease: systematic review].

PubMed

Ródenas Esteve, Irene; Wanden-Berghe, Carmina; Sanz-Valero, Javier

2018-01-19

To review the available scientific literature about the effects of nutritional status on the multiple sclerosis disease. A systematic review of the scientific literature in the Medline (PubMed), Scopus, Cochrane Library and Web of Science databases through November 2016. Search equation: ("Multiple Sclerosis"[Mesh] OR "Multiple Sclerosis"[Title/Abstract] OR "Disseminated Sclerosis"[Title/Abstract] OR "Multiple Sclerosis Acute Fulminating"[Title/Abstract]) AND ("Nutritional Status"[Mesh] OR "Nutritional Status"[Title/Abstract] OR "Nutrition Status"[Title/Abstract]). The quality of the selected articles was discussed using the STROBE questionnaire. The search was completed through experts inquiry and additional review of the bibliographic references included in the selected papers. The concordance between authors (Kappa index) had to be higher than 80% for inclusion in this review. Of the 160 references recovered, after applying inclusion and exclusion criteria, 29 articles were selected for review. Concordance between evaluators was 100.00%. The most studies established vitamin D levels. Others focused their research on finding out which nutrient deficits might be related to the multiple sclerosis development. Vitamin D may influence multiple sclerosis improvement. Sunlight and physical activity would be important factors, with nutritional status, in the course of this disease. It is necessary to produce new specific works that will delve into the subject to find out more about the relationship between nutritional status and multiple sclerosis.

Multiple sclerosis - discharge

MedlinePlus

... this page: //medlineplus.gov/ency/patientinstructions/000129.htm Multiple sclerosis - discharge To use the sharing features on this ... Your doctor has told you that you have multiple sclerosis (MS). This disease affects the brain and spinal ...

Multiple Sclerosis: Can It Cause Seizures?

MedlinePlus

... Is there any connection between multiple sclerosis and epilepsy? Answers from B Mark Keegan, M.D. Epileptic ... E, et al. The prevalence and characteristics of epilepsy in patients with multiple sclerosis in Nordland County, ...

Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional MRI

DTIC Science & Technology

2015-10-01

Page | 2 AWARD NUMBER: W81XWH-13-1-0464 TITLE: Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional MRI...Sep 2014 – 29 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional...findings include: 1) detection of brain organization in a cohort of 24 pediatric onset multiple sclerosis patients (POMS) and 25 healthy controls

Plasma Endothelial Microparticles in Multiple Sclerosis: A Novel Metric Assay of Disease Activity and Response to Treatment

DTIC Science & Technology

2011-09-01

direct link to a source of increased tissue iron deposition which is characteristic for multiple sclerosis . The results of these data and their... Multiple Sclerosis : A Novel Metric Assay of Disease Activity and Response to Treatment PRINCIPAL INVESTIGATOR: Jonathan Steven...SUBTITLE 5a. CONTRACT NUMBER Plasma Endothelial Microparticles in Multiple Sclerosis : A Novel Metric Assay of Disease Activity and Response to

Living with uncertainty and hope: A qualitative study exploring parents' experiences of living with childhood multiple sclerosis.

PubMed

Hinton, Denise; Kirk, Susan

2017-06-01

Background There is growing recognition that multiple sclerosis is a possible, albeit uncommon, diagnosis in childhood. However, very little is known about the experiences of families living with childhood multiple sclerosis and this is the first study to explore this in depth. Objective Our objective was to explore the experiences of parents of children with multiple sclerosis. Methods Qualitative in-depth interviews with 31 parents using a grounded theory approach were conducted. Parents were sampled and recruited via health service and voluntary sector organisations in the United Kingdom. Results Parents' accounts of life with childhood multiple sclerosis were dominated by feelings of uncertainty associated with four sources; diagnostic uncertainty, daily uncertainty, interaction uncertainty and future uncertainty. Parents attempted to manage these uncertainties using specific strategies, which could in turn create further uncertainties about their child's illness. However, over time, ongoing uncertainty appeared to give parents hope for their child's future with multiple sclerosis. Conclusion Illness-related uncertainties appear to play a role in generating hope among parents of a child with multiple sclerosis. However, this may lead parents to avoid sources of information and support that threatens their fragile optimism. Professionals need to be sensitive to the role hope plays in supporting parental coping with childhood multiple sclerosis.

What's new in multiple sclerosis spasticity research? Poster session highlights.

PubMed

Linker, Ralf

2017-11-01

Each year at the Multiple Sclerosis Experts Summit, relevant research in the field of multiple sclerosis spasticity is featured in poster sessions. The main studies presented at this year's meeting are summarized herein.

Accelerated Cure Project for Multiple Sclerosis

MedlinePlus

... main content Accelerating research toward a cure for multiple sclerosis Toggle navigation Search form Search Connect Volunteer Donate ... is to accelerate efforts toward a cure for multiple sclerosis by rapidly advancing research that determines its causes ...

Symptomatic treatment in multiple sclerosis-interim analysis of a nationwide registry.

PubMed

Skierlo, S; Rommer, P S; Zettl, U K

2017-04-01

To analyze symptomatic treatment in patients with multiple sclerosis (MS). Multiple sclerosis is a chronic inflammatory disease of the central nervous system, with accumulating disability symptoms like spasticity, voiding disorders, depression, and pain might occur. The nationwide German MS registry was initiated 2001 under guidance of the German MS society (Deutsche MS Gesellschaft). This study was performed as an interim analysis to lay foundation for future work on this topic. A subcohort of 5113 patients was assessed for this interim analysis. The mean age of the patients was 45.3 years; mean EDSS was 4.2. More than two-third of the enrolled patients were females (70.9%). Most frequent symptoms were fatigue (60%), followed by spasticity (52.5%) and voiding disorders (51.7%). The likelihood of treatment was highest for epileptic disorders (68.8%), spasticity (68.5%), pain (60.7%), and depression (58.9%). Multivariate regression analysis showed that retirement was the strongest factor predictive for antispastic treatment (β=.061, P=.005). Almost all patients in this analysis suffer from symptoms due to advanced MS. Treatment for the various symptoms differed tremendously. The likelihood of treatment correlated with the availability of effective therapeutic agents. Clinicians should put more awareness on MS symptoms. Symptomatic treatment may improve quality of life. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effectiveness of monopolar dielectric transmission of pulsed electromagnetic fields for multiple sclerosis-related pain: A pilot study.

PubMed

Hochsprung, A; Escudero-Uribe, S; Ibáñez-Vera, A J; Izquierdo-Ayuso, G

2018-05-08

Pain is highly prevalent in patients with multiple sclerosis (MS); it is chronic in 50% of cases and is classified as nociceptive, neuropathic, or mixed-type. Pain affects quality of life, sleep, and the activities of daily living. Electrotherapy is an interesting alternative or complementary treatment in the management of pain in MS, with new innovations constantly appearing. This study evaluates the effectiveness of treatment with monopolar dielectric transmission of pulsed electromagnetic fields (PEMF) for pain associated with MS. We performed a randomised, placebo-controlled clinical trial including 24 patients, who were assessed with the Brief Pain Inventory, the Multiple Sclerosis International Quality of Life questionnaire, the Beck Depression Inventory, and the Modified Fatigue Impact Scale. Statistically significant improvements were observed in maximum and mean pain scores, as well as in the impact of pain on work, personal relationships, and sleep and rest. Not significant differences were found between the treatment and placebo groups. Treatment with PEMF may be effective in reducing pain in patients with MS, although further research is necessary to confirm its effectiveness over placebo and to differentiate which type of pain may be more susceptible to this treatment. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Pediatric Multiple Sclerosis: Genes, Environment, and a Comprehensive Therapeutic Approach.

PubMed

Cappa, Ryan; Theroux, Liana; Brenton, J Nicholas

2017-10-01

Pediatric multiple sclerosis is an increasingly recognized and studied disorder that accounts for 3% to 10% of all patients with multiple sclerosis. The risk for pediatric multiple sclerosis is thought to reflect a complex interplay between environmental and genetic risk factors. Environmental exposures, including sunlight (ultraviolet radiation, vitamin D levels), infections (Epstein-Barr virus), passive smoking, and obesity, have been identified as potential risk factors in youth. Genetic predisposition contributes to the risk of multiple sclerosis, and the major histocompatibility complex on chromosome 6 makes the single largest contribution to susceptibility to multiple sclerosis. With the use of large-scale genome-wide association studies, other non-major histocompatibility complex alleles have been identified as independent risk factors for the disease. The bridge between environment and genes likely lies in the study of epigenetic processes, which are environmentally-influenced mechanisms through which gene expression may be modified. This article will review these topics to provide a framework for discussion of a comprehensive approach to counseling and ultimately treating the pediatric patient with multiple sclerosis. Copyright © 2017 Elsevier Inc. All rights reserved.

[Living with a chronic progressive form of multiple sclerosis--a balance act].

PubMed

Hellige, Barbara

2002-12-01

There are only a few studies in the German speaking countries available which address the subject of the experience of chronically ill people during the course of their illness. Therefore it was the intent of this present study to find answers for central nurse science issues: How do people who suffer from a chronically progressive course of multiple sclerosis experience the downward trajectory? Which strategies do they develop in order to integrate the disease into their lives? In what ways does the scientific paradigm of medicine influence the perceptions of the illness and the life with it? After an analysis of the national and international state of nursing research follows a description of the methodology of the Grounded Theory and the individual examination steps of the study. The second part examines some essentials of the study. The results show that the trajectory is characterized by four phases. At first the ill person concentrates on the social discussion of the pathogenesis and the medical paradigma. But with physical experiences, exchange with other affected people and acquired information, those concerned develop a very case-specific knowledge. Often disillusioned by the medication strategies, based on the experience that their subjectivity and their individuality are not taken into account, they increasingly disapprove the deficit-oriented perspective of the professionals. They develop distinctly self-caring potentialities. To identify and support this self-care potentialities should be the very core of nursing.

Cannabis use by individuals with multiple sclerosis: effects on specific immune parameters.

PubMed

Sexton, Michelle; Cudaback, Eiron; Abdullah, Rehab A; Finnell, John; Mischley, Laurie K; Rozga, Mary; Lichtman, Aron H; Stella, Nephi

2014-10-01

Cannabinoids affect immune responses in ways that may be beneficial for autoimmune diseases. We sought to determine whether chronic Cannabis use differentially modulates a select number of immune parameters in healthy controls and individuals with multiple sclerosis (MS cases). Subjects were enrolled and consented to a single blood draw, matched for age and BMI. We measured monocyte migration isolated from each subject, as well as plasma levels of endocannabinoids and cytokines. Cases met definition of MS by international diagnostic criteria. Monocyte cell migration measured in control subjects and individuals with MS was similarly inhibited by a set ratio of phytocannabinoids. The plasma levels of CCL2 and IL17 were reduced in non-naïve cannabis users irrespective of the cohorts. We detected a significant increase in the endocannabinoid arachidonoylethanolamine (AEA) in serum from individuals with MS compared to control subjects, and no significant difference in levels of other endocannabinoids and signaling lipids irrespective of Cannabis use. Chronic Cannabis use may affect the immune response to similar extent in individuals with MS and control subjects through the ability of phytocannabinoids to reduce both monocyte migration and cytokine levels in serum. From a panel of signaling lipids, only the levels of AEA are increased in individuals with MS, irrespective of Cannabis use or not. Our results suggest that both MS cases and controls respond similarly to chronic Cannabis use with respect to the immune parameters measured in this study.

CANNABIS USE BY INDIVIDUALS WITH MULTIPLE SCLEROSIS: EFFECTS ON SPECIFIC IMMUNE PARAMETERS

PubMed Central

Sexton, Michelle; Cudaback, Eiron; Abdullah, Rehab A.; Finnell, John; Mischley, Laurie K; Rozga, Mary; Lichtman, Aron H.; Stella, Nephi

2014-01-01

Cannabinoids affect immune responses in ways that may be beneficial for autoimmune diseases. We sought to determine whether chronic Cannabis use differentially modulates a select number of immune parameters in healthy controls and individuals with multiple sclerosis (MS cases). Subjects were enrolled and consented to a single blood draw, matched for age and BMI. We measured monocyte migration isolated from each subject, as well as plasma levels of endocannabinoids and cytokines. Cases met definition of MS by international diagnostic criteria. Monocyte cell migration measured in control subjects and individuals with MS were similarly inhibited by a set ratio of phytocannabinoids. The plasma levels of CCL2 and IL17 were reduced in non-naïve cannabis users irrespective of the cohorts. We detected a significant increase in the endocannabinoid arachidonoylethanolamine (AEA) in serum from individuals with MS compared to control subjects, and no significant difference in levels of other endocannabinoids and signaling lipids irrespective of Cannabis use. Chronic Cannabis use may affect the immune response to similar extent in individuals with MS and control subjects through the ability of phytocannabinoids to reduce both monocyte migration and cytokine levels in serum. From a panel of signaling lipids, only the levels of AEA are increased in individuals with MS, irrespective from Cannabis use or not. Our results suggest that both MS cases and controls respond similarly to chronic Cannabis use with respect to the immune parameters measured in this study. PMID:25135301

78 FR 17613 - Special Local Regulations and Safety Zones; Recurring Events in Northern New England

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-22

... Multiple Sclerosis Event Type: Regatta and Sailboat Regatta. Race Sponsor: Maine Chapter, Multiple...]13'51'' W 8.7 Multiple Sclerosis Event Type: Power Boat Race Harborfest Lobster Boat/ Sponsor: Maine Chapter, National Tugboat Races. Multiple Sclerosis Society [[Page 17619

Differential diagnosis of Mendelian and mitochondrial disorders in patients with suspected multiple sclerosis

PubMed Central

Katz Sand, Ilana B.; Honce, Justin M.; Lublin, Fred D.

2015-01-01

Several single gene disorders share clinical and radiologic characteristics with multiple sclerosis and have the potential to be overlooked in the differential diagnostic evaluation of both adult and paediatric patients with multiple sclerosis. This group includes lysosomal storage disorders, various mitochondrial diseases, other neurometabolic disorders, and several other miscellaneous disorders. Recognition of a single-gene disorder as causal for a patient’s ‘multiple sclerosis-like’ phenotype is critically important for accurate direction of patient management, and evokes broader genetic counselling implications for affected families. Here we review single gene disorders that have the potential to mimic multiple sclerosis, provide an overview of clinical and investigational characteristics of each disorder, and present guidelines for when clinicians should suspect an underlying heritable disorder that requires diagnostic confirmation in a patient with a definite or probable diagnosis of multiple sclerosis. PMID:25636970

Melorheostosis with bilateral involvement in a black African patient.

PubMed

Biaou, Olivier; Avimadje, Martin; Guira, Oumar; Adjagba, Alex; Zannou, Marcel; Hauzeur, Jean-Philippe

2004-01-01

Melorheostosis is a rare chronic bone disease of unknown etiology that often affects a single limb. Onset usually occurs in childhood or early adolescence. A flowing wax appearance along the surface of the bone and multiple areas of bone sclerosis produce a typical radiographic picture. We describe the first case reported in a black African, in whom an exceedingly rare feature was a bilateral distribution of the lesions.

[A different approach to the care of patients with MS].

PubMed

Moulin, Denis; Bonansea, Gilles; Calmels, Martine; Lefort, Hugues; Le Nédic, Christelle

2016-03-01

Therapeutic patient education comprises multi-disciplinary support to help patients accept and manage a chronic pathology. Nurses are at the heart of this team approach. Two nurses from Brest military teaching hospital share their experience in this field with patients with multiple sclerosis, which provides benefits for the patient as well as added value for a reflexive nursing practice. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The Bug Stops Here: Force Protection and Emerging Infectious Diseases

DTIC Science & Technology

2005-11-01

said in 1972 that “the future of infectious diseases will be very dull.” Successful vaccines against smallpox and polio only furthered belief that...probably higher. Mounting evidence implicates microbes in heart disease, rheumatoid arthritis, diabetes, multiple sclerosis, autism , chronic lung diseases...cross protection against smallpox. Louis Pasteur later adopted the word ‘ vaccination ’ for immunization against any disease. 19 “History of Military

Does environmental confounding mask pleiotropic effects of a multiple sclerosis susceptibility variant on vitamin D in psychosis?

PubMed

Iyegbe, Conrad O; Acharya, Anita; Lally, John; Gardner-Sood, Poonam; Smith, Louise S; Smith, Shubulade; Murray, Robin; Howes, Oliver; Gaughran, Fiona

2015-01-01

This work addresses the existing and emerging evidence of overlap within the environmental and genetic profiles of multiple sclerosis (MS) and schizophrenia. To investigate whether a genetic risk factor for MS (rs703842), whose variation is indicative of vitamin D status in the disorder, could also be a determinant of vitamin D status in chronic psychosis patients. A cohort of 224 chronic psychosis cases was phenotyped and biologically profiled. The relationship between rs703842 and physiological vitamin D status in the blood plasma was assessed by logistic regression. Deficiency was defined as a blood plasma concentration below 10 ng/µl. Potential environmental confounders of the vitamin D status were considered as part of the analysis. We report suggestive evidence of an association with vitamin D status in established psychosis (ß standardized=0.51, P=0.04). The logistic model fit significantly benefited from controlling for body mass index, depression and ethnicity (χ (2)=91.7; 2 degrees of freedom (df); P=1.2×10(20)). The results suggest that, in addition to lifestyle changes that accompany the onset of illness, vitamin D dysregulation in psychosis has a genetic component that links into MS. Further, comprehensive studies are needed to evaluate this prospect.

Characteristics of patients seeking health information online via social health networks versus general Internet sites: a comparative study.

PubMed

Magnezi, Racheli; Grosberg, Dafna; Novikov, Ilya; Ziv, Arnona; Shani, Mordechai; Freedman, Laurence S

2015-03-01

Camoni.co.il, a Hebrew-language social health network offers advice, consultation, and connection to others with chronic illness. This study compared characteristics and objectives of Camoni.co.il users and individuals seeking medical information through general Internet sites. Similar questionnaires were sent to 1009 Internet and 900 Camoni users. Cluster analysis defined four modes of online social health network use: "acquiring information and support", "communicating", "networking" and "browsing". Six hundred and five Internet and 125 Camoni users responded. Diabetes, hypertension, obesity and lung diseases were found more often among general Internet users than Camoni users. Among Camoni users, "acquiring information and support" was the main motivation for individuals over age 55 years, women, those with lower income, chronic pain, obesity and depression. "Communicating" was the main incentive of men, those 20-34 years old, those with less education, or an eating disorder. "Networking" was the most significant motivation for those with multiple sclerosis or depression. Browsing was most frequent among individuals with multiple sclerosis. Identifying needs of social health network surfers will allow planning unique contents and enhancing social health sites. Physicians might advise patients to use them to obtain support and information regarding their conditions, possibly leading to improved compliance and self-management.

Fibrinogen is not elevated in the cerebrospinal fluid of patients with multiple sclerosis

PubMed Central

2011-01-01

Background Elevated plasma fibrinogen levels are a well known finding in acute infectious diseases, acute stroke and myocardial infarction. However its role in the cerebrospinal fluid (CSF) of acute and chronic central (CNS) and peripheral nervous system (PNS) diseases is unclear. Findings We analyzed CSF and plasma fibrinogen levels together with routine parameters in patients with multiple sclerosis (MS), acute inflammatory diseases of the CNS (bacterial and viral meningoencephalitis, BM and VM) and PNS (Guillain-Barré syndrome; GBS), as well as in non-inflammatory neurological controls (OND) in a total of 103 patients. Additionally, MS patients underwent cerebral MRI scans at time of lumbar puncture. CSF and plasma fibrinogen levels were significantly lower in patients with MS and OND patients as compared to patients with BM, VM and GBS. There was a close correlation between fibrinogen levels and albumin quotient (rho = 0.769, p < 0.001) which strongly suggests passive transfer of fibrinogen through the blood-CSF-barrier during acute inflammation. Hence, in MS, the prototype of chronic neuroinflammation, CSF fibrinogen levels were not elevated and could not be correlated to clinical and neuroradiological outcome parameters. Conclusions Although previous work has shown clear evidence of the involvement of fibrinogen in MS pathogenesis, this is not accompanied by increased fibrinogen in the CSF compartment. PMID:22029888

Multiple Sclerosis/Chronic Fatigue Syndrome overlap: When two common disorders collide.

PubMed

Gaber, Tarek A-Z K; Oo, Wah Wah; Ringrose, Hollie

2014-01-01

Fatigue is a major cause of disability and handicap in Multiple Sclerosis (MS) patients. The management of this common problem is often difficult. Chronic Fatigue Syndrome (CFS/ME) is another common cause of fatigue which is prevalent in the same population of middle aged females commonly affected by MS. This report aims at examining the potential coexistence of MS and CFS/ME in the same patients. This is a retrospective study examining a cohort of MS patients referred for rehabilitation. The subjects were screened for CFS/ME symptoms. Sixty-four MS patients (43 females) were screened for CFS/ME. Nine patients (14%) with a mean age 52 (SD 9.7) who were all females fulfilled the Fukuda criteria for diagnosis of CFS/ME. Their symptoms, including muscular and joint pain, malaise and recurrent headaches, were not explained by the pattern of their MS. MS and CFS/ME are two common conditions with increased prevalence in middle aged females. As the diagnosis of CFS/ME is clinical with no positive clinical signs or investigations; it can be made with difficulty in the presence of another clear explanation for the disabling fatigue. Our results suggest that the two conditions may co-exist. Considering CFS/ME as a potential co-morbidity may lead to more focused and appropriate management.

Molecular cloning of human T-cell lymphotrophic virus type I-like proviral genome from the peripheral lymphocyte DNA of a patient with chronic neurologic disorders.

PubMed Central

Reddy, E P; Mettus, R V; DeFreitas, E; Wroblewska, Z; Cisco, M; Koprowski, H

1988-01-01

Human T-cell lymphotropic virus type 1 (HTLV-I), the etiologic agent of human T-cell leukemia, has recently been shown to be associated with neurologic disorders such as tropical spastic paraparesis, HTLV-associated myelopathy, and possibly with multiple sclerosis. In this communication, we have examined one specific case of neurologic disorder that can be classified as multiple sclerosis or tropical spastic paraparesis. The patient suffering from chronic neurologic disorder was found to contain antibodies to HTLV-I envelope and gag proteins in his serum and cerebrospinal fluid. Lymphocytes from peripheral blood and cerebrospinal fluid of the patient were shown to express viral RNA sequences by in situ hybridization. Southern blot analysis of the patient lymphocyte DNA revealed the presence of HTLV-I-related sequences. Blot-hybridization analysis of the RNA from fresh peripheral lymphocytes stimulated with interleukin 2 revealed the presence of abundant amounts of genomic viral RNA with little or no subgenomic RNA. We have cloned the proviral genome from the DNA of the peripheral lymphocytes and determined its restriction map. This analysis shows that this proviral genome is very similar if not identical to that of the prototype HTLV-I genome. Images PMID:2897123

Considerations on long-term immuno-intervention in the treatment of multiple sclerosis: an expert opinion.

PubMed

Grigoriadis, Nikolaos; Linnebank, Michael; Alexandri, Nektaria; Muehl, Sarah; Hofbauer, Günther F L

2016-10-01

As management of multiple sclerosis (MS) requires life-long treatment with disease-modifying agents, any risks associated with long-term use should be considered when evaluating therapeutic options. Immune cells of the innate and adaptive immune systems play various roles in the pathogenesis of MS. MS therapies affect the immune system, each with a unique mode of action, and consequently possess different long-term safety profiles. Rare, but serious safety concerns, including an increased risk of infection and cancer, have been associated with immunosuppressant use. The risks associated with newer immunosuppressive agents, which target specific elements of MS disease pathophysiology, are not yet fully established as the duration of clinical trials is relatively short and post-marketing experience is limited. Non-immunosuppressants used to treat MS have well-defined safety profiles established over a large number of patient-years demonstrating them to be well-tolerated long-term treatment options. When considering the long-term use of disease-modifying agents for treating MS, classification as immunosuppressants or non-immunosuppressants can be useful when evaluating potential risks associated with chronic use. A successful therapeutic strategy for any serious, chronic disease such as MS should weigh effectiveness versus long-term safety of available treatments.

Impaired neurosteroid synthesis in multiple sclerosis

PubMed Central

Noorbakhsh, Farshid; Ellestad, Kristofor K.; Maingat, Ferdinand; Warren, Kenneth G.; Han, May H.; Steinman, Lawrence; Baker, Glen B.

2011-01-01

High-throughput technologies have led to advances in the recognition of disease pathways and their underlying mechanisms. To investigate the impact of micro-RNAs on the disease process in multiple sclerosis, a prototypic inflammatory neurological disorder, we examined cerebral white matter from patients with or without the disease by micro-RNA profiling, together with confirmatory reverse transcription–polymerase chain reaction analysis, immunoblotting and gas chromatography-mass spectrometry. These observations were verified using the in vivo multiple sclerosis model, experimental autoimmune encephalomyelitis. Brains of patients with or without multiple sclerosis demonstrated differential expression of multiple micro-RNAs, but expression of three neurosteroid synthesis enzyme-specific micro-RNAs (miR-338, miR-155 and miR-491) showed a bias towards induction in patients with multiple sclerosis (P < 0.05). Analysis of the neurosteroidogenic pathways targeted by micro-RNAs revealed suppression of enzyme transcript and protein levels in the white matter of patients with multiple sclerosis (P < 0.05). This was confirmed by firefly/Renilla luciferase micro-RNA target knockdown experiments (P < 0.05) and detection of specific micro-RNAs by in situ hybridization in the brains of patients with or without multiple sclerosis. Levels of important neurosteroids, including allopregnanolone, were suppressed in the white matter of patients with multiple sclerosis (P < 0.05). Induction of the murine micro-RNAs, miR-338 and miR-155, accompanied by diminished expression of neurosteroidogenic enzymes and allopregnanolone, was also observed in the brains of mice with experimental autoimmune encephalomyelitis (P < 0.05). Allopregnanolone treatment of the experimental autoimmune encephalomyelitis mouse model limited the associated neuropathology, including neuroinflammation, myelin and axonal injury and reduced neurobehavioral deficits (P < 0.05). These multi-platform studies point to impaired neurosteroidogenesis in both multiple sclerosis and experimental autoimmune encephalomyelitis. The findings also indicate that allopregnanolone and perhaps other neurosteroid-like compounds might represent potential biomarkers or therapies for multiple sclerosis. PMID:21908875

The comparison of socio-economic conditions and personal hygiene habits of neuro-Behçet's disease and multiple sclerosis patients.

PubMed

Pehlivan, Münevver; Kürtüncü, Murat; Tüzün, Erdem; Shugaiv, Erkingül; Mutlu, Melike; Eraksoy, Mefküre; Akman-Demir, Gülşen

2011-07-01

The "hygiene hypothesis" suggests that a reduction in the exposure to infectious agents due to improved health conditions has contributed to the increased incidence of autoimmune disorders in developed countries. In keeping with the hygiene hypothesis, many autoimmune disorders such as multiple sclerosis (MS) are more frequently observed in developed countries. To identify the relevance of hygiene hypothesis in neuro-Behçet's disease (NBD), another chronic inflammatory disease of the central nervous system, we developed and administered a multiple choice questionnaire to evaluate the hygiene conditions and practices of age and gender-matched NBD patients (n = 50) and control MS (n =5 0) and headache (n = 50) patients. Overall, MS patients had the highest socio-economic and hygiene features, whereas NBD patients displayed a lower socio-economic status group and showed poorer hygiene conditions than MS and headache controls. These poor hygiene conditions might be increasing the susceptibility of exposure to infectious agents that might, at least in part, trigger the inflammatory responses involved in NBD pathogenesis. Copyright © 2011 Elsevier GmbH. All rights reserved.

Vitamin D and Multiple Sclerosis (MS): Is There Any Connection?

MedlinePlus

... protective effect and lower the risk of developing multiple sclerosis (MS). Another study conducted at Maastricht University in ... D. Raghuwanshi A, et al. Vitamin D and multiple sclerosis. Journal of Cell Biochemistry. 2008;105:338. Ramagopalan ...

Searching for neurodegeneration in multiple sclerosis at clinical onset: Diagnostic value of biomarkers.

PubMed

Novakova, Lenka; Axelsson, Markus; Malmeström, Clas; Imberg, Henrik; Elias, Olle; Zetterberg, Henrik; Nerman, Olle; Lycke, Jan

2018-01-01

Neurodegeneration occurs during the early stages of multiple sclerosis. It is an essential, devastating part of the pathophysiology. Tools for measuring the degree of neurodegeneration could improve diagnostics and patient characterization. This study aimed to determine the diagnostic value of biomarkers of degeneration in patients with recent clinical onset of suspected multiple sclerosis, and to evaluate these biomarkers for characterizing disease course. This cross-sectional study included 271 patients with clinical features of suspected multiple sclerosis onset and was the baseline of a prospective study. After diagnostic investigations, the patients were classified into the following disease groups: patients with clinically isolated syndrome (n = 4) or early relapsing remitting multiple sclerosis (early RRMS; n = 93); patients with relapsing remitting multiple sclerosis with disease durations ≥2 years (established RRMS; n = 39); patients without multiple sclerosis, but showing symptoms (symptomatic controls; n = 89); and patients diagnosed with other diseases (n = 46). In addition, we included healthy controls (n = 51) and patients with progressive multiple sclerosis (n = 23). We analyzed six biomarkers of neurodegeneration: cerebrospinal fluid neurofilament light chain levels; cerebral spinal fluid glial fibrillary acidic protein; cerebral spinal fluid tau; retinal nerve fiber layer thickness; macula volume; and the brain parenchymal fraction. Except for increased cerebral spinal fluid neurofilament light chain levels, median 670 ng/L (IQR 400-2110), we could not find signs of early degeneration in the early disease group with recent clinical onset. However, the intrathecal immunoglobin G production and cerebral spinal fluid neurofilament light chain levels showed diagnostic value. Moreover, elevated levels of cerebral spinal fluid glial fibrillary acidic protein, thin retinal nerve fiber layers, and low brain parenchymal fractions were associated with progressive disease, but not with the other phenotypes. Thin retinal nerve fiber layers and low brain parenchymal fractions, which indicated neurodegeneration, were associated with longer disease duration. In clinically suspected multiple sclerosis, intrathecal immunoglobin G production and neurofilament light chain levels had diagnostic value. Therefore, these biomarkers could be included in diagnostic work-ups for multiple sclerosis. We found that the thickness of the retinal nerve fiber layer and the brain parenchymal fraction were not different between individuals that were healthy, symptomatic, or newly diagnosed with multiple sclerosis. This finding suggested that neurodegeneration had not reached a significant magnitude in patients with a recent clinical onset of multiple sclerosis.

Peginterferon beta-1a reduces the evolution of MRI lesions to black holes in patients with RRMS: a post hoc analysis from the ADVANCE study.

PubMed

Arnold, Douglas L; You, Xiaojun; Castrillo-Viguera, Carmen

2017-08-01

The presence of chronic black holes, i.e., chronic lesions that are hypointense on T1-weighted images and are indicative of more severe tissue injury, has been increasingly utilized as a surrogate marker of therapeutic outcome in multiple sclerosis. The ADVANCE study was a 2-year, double-blind, pivotal trial evaluating the safety and efficacy of subcutaneous peginterferon beta-1a 125 mcg in 1512 patients with relapsing-remitting multiple sclerosis (RRMS). This report describes the correlation of clinical outcomes with the evolution of acute lesions into chronic black holes in ADVANCE, and the efficacy of peginterferon beta-1a in reducing this evolution. Treatment with peginterferon beta-1a significantly reduced the mean number of new/enlarging T2-weighted (NET2) lesions (0.76 vs. 1.03 from week 24, p = 0.0037; 0.44 vs. 0.99 from week 48, p < 0.0001) and new gadolinium-enhancing (Gd+) lesions (0.15 vs. 0.32 from week 24, p < 0.0001; 0.09 vs. 0.19 from week 48) that evolved into chronic black holes by 2 years. Patients with NET2 or Gd+ lesions at 24 weeks that evolved into chronic black holes showed significantly worse clinical outcomes, including a greater proportion with 12-week (14.9 vs. 8.4%; p = 0.0167) and 24-week (12.3 vs. 7.0%; p = 0.0333) confirmed disability worsening and higher mean annualized relapse rate (0.62 vs. 0.43; p = 0.0118), compared with patients with lesions that did not evolve into black holes. The correlation was independent of treatment. Reduced risk of evolution of new lesions into chronic black holes with peginterferon beta-1a treatment suggests potential to reduce long-term disability in RRMS by preventing irreversible tissue damage.

Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-1-0524 TITLE:Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis PRINCIPAL INVESTIGATOR: Jeffrey D...29 Sep 2015 4. TITLE AND SUBTITLE Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis 5a. CONTRACT NUMBER W81XWH-14-1-0524...MCT1 in injured oligodendroglia of multiple sclerosis patients contributes to axon neurodegeneration and that increasing MCT1 will be protective in the

Gut microbiota in multiple sclerosis: possible influence of immunomodulators.

PubMed

Cantarel, Brandi L; Waubant, Emmanuelle; Chehoud, Christel; Kuczynski, Justin; DeSantis, Todd Z; Warrington, Janet; Venkatesan, Arun; Fraser, Claire M; Mowry, Ellen M

2015-06-01

Differences in gut bacteria have been described in several autoimmune disorders. In this exploratory pilot study, we compared gut bacteria in patients with multiple sclerosis and healthy controls and evaluated the influence of glatiramer acetate and vitamin D treatment on the microbiota. Subjects were otherwise healthy white women with or without relapsing-remitting multiple sclerosis who were vitamin D insufficient. Patients with multiple sclerosis were untreated or were receiving glatiramer acetate. Subjects collected stool at baseline and after 90 days of vitamin D3 (5000 IU/d) supplementation. The abundance of operational taxonomic units was evaluated by hybridization of 16S rRNA to a DNA microarray. While there was overlap of gut bacterial communities, the abundance of some operational taxonomic units, including Faecalibacterium, was lower in patients with multiple sclerosis. Glatiramer acetate-treated patients with multiple sclerosis showed differences in community composition compared with untreated subjects, including Bacteroidaceae, Faecalibacterium, Ruminococcus, Lactobacillaceae, Clostridium, and other Clostridiales. Compared with the other groups, untreated patients with multiple sclerosis had an increase in the Akkermansia, Faecalibacterium, and Coprococcus genera after vitamin D supplementation. While overall bacterial communities were similar, specific operational taxonomic units differed between healthy controls and patients with multiple sclerosis. Glatiramer acetate and vitamin D supplementation were associated with differences or changes in the microbiota. This study was exploratory, and larger studies are needed to confirm these preliminary results.

SUMMIT (Serially Unified Multicenter Multiple Sclerosis Investigation): creating a repository of deeply phenotyped contemporary multiple sclerosis cohorts.

PubMed

Bove, Riley; Chitnis, Tanuja; Cree, Bruce Ac; Tintoré, Mar; Naegelin, Yvonne; Uitdehaag, Bernard Mj; Kappos, Ludwig; Khoury, Samia J; Montalban, Xavier; Hauser, Stephen L; Weiner, Howard L

2017-08-01

There is a pressing need for robust longitudinal cohort studies in the modern treatment era of multiple sclerosis. Build a multiple sclerosis (MS) cohort repository to capture the variability of disability accumulation, as well as provide the depth of characterization (clinical, radiologic, genetic, biospecimens) required to adequately model and ultimately predict a patient's course. Serially Unified Multicenter Multiple Sclerosis Investigation (SUMMIT) is an international multi-center, prospectively enrolled cohort with over a decade of comprehensive follow-up on more than 1000 patients from two large North American academic MS Centers (Brigham and Women's Hospital (Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB; BWH)) and University of California, San Francisco (Expression/genomics, Proteomics, Imaging, and Clinical (EPIC))). It is bringing online more than 2500 patients from additional international MS Centers (Basel (Universitätsspital Basel (UHB)), VU University Medical Center MS Center Amsterdam (MSCA), Multiple Sclerosis Center of Catalonia-Vall d'Hebron Hospital (Barcelona clinically isolated syndrome (CIS) cohort), and American University of Beirut Medical Center (AUBMC-Multiple Sclerosis Interdisciplinary Research (AMIR)). We provide evidence for harmonization of two of the initial cohorts in terms of the characterization of demographics, disease, and treatment-related variables; demonstrate several proof-of-principle analyses examining genetic and radiologic predictors of disease progression; and discuss the steps involved in expanding SUMMIT into a repository accessible to the broader scientific community.

Addressing the targeting range of the ABILHAND-56 in relapsing-remitting multiple sclerosis: A mixed methods psychometric study.

PubMed

Cleanthous, Sophie; Strzok, Sara; Pompilus, Farrah; Cano, Stefan; Marquis, Patrick; Cohan, Stanley; Goldman, Myla D; Kresa-Reahl, Kiren; Petrillo, Jennifer; Castrillo-Viguera, Carmen; Cadavid, Diego; Chen, Shih-Yin

2018-01-01

ABILHAND, a manual ability patient-reported outcome instrument originally developed for stroke patients, has been used in multiple sclerosis clinical trials; however, psychometric analyses indicated the measure's limited measurement range and precision in higher-functioning multiple sclerosis patients. The purpose of this study was to identify candidate items to expand the measurement range of the ABILHAND-56, thus improving its ability to detect differences in manual ability in higher-functioning multiple sclerosis patients. A step-wise mixed methods design strategy was used, comprising two waves of patient interviews, a combination of qualitative (concept elicitation and cognitive debriefing) and quantitative (Rasch measurement theory) analytic techniques, and consultation interviews with three clinical neurologists specializing in multiple sclerosis. Original ABILHAND was well understood in this context of use. Eighty-two new manual ability concepts were identified. Draft supplementary items were generated and refined with patient and neurologist input. Rasch measurement theory psychometric analysis indicated supplementary items improved targeting to higher-functioning multiple sclerosis patients and measurement precision. The final pool of Early Multiple Sclerosis Manual Ability items comprises 20 items. The synthesis of qualitative and quantitative methods used in this study improves the ABILHAND content validity to more effectively identify manual ability changes in early multiple sclerosis and potentially help determine treatment effect in higher-functioning patients in clinical trials.

A Systematic Review and Meta-Analysis of Strength Training in Individuals With Multiple Sclerosis Or Parkinson Disease

PubMed Central

Cruickshank, Travis M.; Reyes, Alvaro R.; Ziman, Melanie R.

2015-01-01

Abstract Strength training has, in recent years, been shown to be beneficial for people with Parkinson disease and multiple sclerosis. Consensus regarding its utility for these disorders nevertheless remains contentious among healthcare professionals. Greater clarity is required, especially in regards to the type and magnitude of effects as well as the response differences to strength training between individuals with Parkinson disease or multiple sclerosis. This study examines the effects, magnitude of those effects, and response differences to strength training between patients with Parkinson disease or multiple sclerosis. A comprehensive search of electronic databases including Physiotherapy Evidence Database scale, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL was conducted from inception to July 2014. English articles investigating the effect of strength training for individuals with neurodegenerative disorders were selected. Strength training trials that met the inclusion criteria were found for individuals with Parkinson disease or multiple sclerosis. Individuals with Parkinson disease or multiple sclerosis were included in the study. Strength training interventions included traditional (free weights/machine exercises) and nontraditional programs (eccentric cycling). Included articles were critically appraised using the Physiotherapy Evidence Database scale. Of the 507 articles retrieved, only 20 articles met the inclusion criteria. Of these, 14 were randomized and 6 were nonrandomized controlled articles in Parkinson disease or multiple sclerosis. Six randomized and 2 nonrandomized controlled articles originated from 3 trials and were subsequently pooled for systematic analysis. Strength training was found to significantly improve muscle strength in people with Parkinson disease (15%–83.2%) and multiple sclerosis (4.5%–36%). Significant improvements in mobility (11.4%) and disease progression were also reported in people with Parkinson disease after strength training. Furthermore, significant improvements in fatigue (8.2%), functional capacity (21.5%), quality of life (8.3%), power (17.6%), and electromyography activity (24.4%) were found in individuals with multiple sclerosis after strength training. The limitations of the study were the heterogeneity of interventions and study outcomes in Parkinson disease and multiple sclerosis trials. Strength training is useful for increasing muscle strength in Parkinson disease and to a lesser extent multiple sclerosis. PMID:25634170

A systematic review and meta-analysis of strength training in individuals with multiple sclerosis or Parkinson disease.

PubMed

Cruickshank, Travis M; Reyes, Alvaro R; Ziman, Melanie R

2015-01-01

Strength training has, in recent years, been shown to be beneficial for people with Parkinson disease and multiple sclerosis. Consensus regarding its utility for these disorders nevertheless remains contentious among healthcare professionals. Greater clarity is required, especially in regards to the type and magnitude of effects as well as the response differences to strength training between individuals with Parkinson disease or multiple sclerosis. This study examines the effects, magnitude of those effects, and response differences to strength training between patients with Parkinson disease or multiple sclerosis. A comprehensive search of electronic databases including Physiotherapy Evidence Database scale, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL was conducted from inception to July 2014. English articles investigating the effect of strength training for individuals with neurodegenerative disorders were selected. Strength training trials that met the inclusion criteria were found for individuals with Parkinson disease or multiple sclerosis. Individuals with Parkinson disease or multiple sclerosis were included in the study. Strength training interventions included traditional (free weights/machine exercises) and nontraditional programs (eccentric cycling). Included articles were critically appraised using the Physiotherapy Evidence Database scale. Of the 507 articles retrieved, only 20 articles met the inclusion criteria. Of these, 14 were randomized and 6 were nonrandomized controlled articles in Parkinson disease or multiple sclerosis. Six randomized and 2 nonrandomized controlled articles originated from 3 trials and were subsequently pooled for systematic analysis. Strength training was found to significantly improve muscle strength in people with Parkinson disease (15%-83.2%) and multiple sclerosis (4.5%-36%). Significant improvements in mobility (11.4%) and disease progression were also reported in people with Parkinson disease after strength training. Furthermore, significant improvements in fatigue (8.2%), functional capacity (21.5%), quality of life (8.3%), power (17.6%), and electromyography activity (24.4%) were found in individuals with multiple sclerosis after strength training. The limitations of the study were the heterogeneity of interventions and study outcomes in Parkinson disease and multiple sclerosis trials. Strength training is useful for increasing muscle strength in Parkinson disease and to a lesser extent multiple sclerosis.

Subcutaneous interferon β-1a three times weekly and the natural evolution of gadolinium-enhancing lesions into chronic black holes in relapsing and progressive multiple sclerosis: Analysis of PRISMS and SPECTRIMS trials.

PubMed

Traboulsee, A; Li, Dkb; Tam, R; Zhao, G; Riddehough, A; Fang, J; Dangond, F; Kappos, L

2017-01-01

Evolution of gadolinium-enhancing lesions into chronic black holes (CBH) may be reduced by interferon (IFN) therapy. The objective of this paper is to assess the effect of IFN β-1a and placebo on CBH evolution and disability in patients with relapsing-remitting multiple sclerosis (RRMS), as well as CBH evolution in patients with secondary progressive multiple sclerosis (SPMS). A post hoc, exploratory analysis of patients with RRMS and SPMS with monthly MRI scans (months -1 to 9) from two separate placebo-controlled clinical trials of IFN β-1a was conducted. In RRMS patients, the risk of ≥1 evolved CBH was lower for IFN β-1a versus placebo (odds ratio 0.42; p  = 0.024); volume of newly evolved CBH was numerically reduced. A numerically higher proportion of patients with ≥1 evolving CBH vs no evolving CBH had confirmed three-month disability progression (four-year rate 55.8% vs 43.1%, respectively). Proportion of lesions evolving into CBH (patient level: 34.7% vs 12.6%, p  < 0.0001; lesion level: 28.8% vs 11.0%, p  < 0.0001) and evolved CBH volume (median 33.5 mm 3 (Quartile 1, 0.0; Quartile 3, 173.4) vs 0.0 mm 3 (0.0; 52.4); p  = 0.0008) was higher for SPMS than RRMS patients treated with IFN β-1a. In RRMS, IFN β-1a significantly decreased the proportion of new T1 Gd+ lesions evolving into CBH and the risk of developing a CBH. In patients with SPMS, more lesions develop to CBH, indicating reduced repair capacity, and the natural history of lesion development appears to be unaffected by IFN β-1a treatment.

Can the Cancer-related Fatigue Case-definition Criteria Be Applied to Chronic Medical Illness? A Comparison between Breast Cancer and Systemic Sclerosis.

PubMed

Kwakkenbos, Linda; Minton, Ollie; Stone, Patrick C; Alexander, Susanna; Baron, Murray; Hudson, Marie; Thombs, Brett D

2015-07-01

Fatigue is a crucial determinant of quality of life across rheumatic diseases, but the lack of agreed-upon standards for identifying clinically significant fatigue hinders research and clinical management. Case definition criteria for cancer-related fatigue were proposed for inclusion in the International Classification of Diseases. The objective was to evaluate whether the cancer-related fatigue case definition performed equivalently in women with breast cancer and systemic sclerosis (SSc) and could be used to identify patients with chronic illness-related fatigue. The cancer-related fatigue interview (case definition criteria met if ≥ 5 of 9 fatigue-related symptoms present with functional impairment) was completed by 291 women with SSc and 278 women successfully treated for breast cancer. Differential item functioning was assessed with the multiple indicator multiple cause model. Items 3 (concentration) and 10 (short-term memory) were endorsed significantly less often by women with SSc compared with cancer, controlling for responses on other items. Omitting these 2 items from the case definition and requiring 4 out of the 7 remaining symptoms resulted in a similar overall prevalence of cancer-related fatigue in the cancer sample compared with the original criteria (37.4% vs 37.8%, respectively), with 97.5% of patients diagnosed identically with both definitions. Prevalence of chronic illness-related fatigue was 36.1% in SSc using 4 of 7 symptoms. The cancer-related fatigue criteria can be used equivalently to identify patients with chronic illness-related fatigue when 2 cognitive fatigue symptoms are omitted. Harmonized definitions and measurement of clinically significant fatigue will advance research and clinical management of fatigue in rheumatic diseases and other conditions.

Modest familial risks for multiple sclerosis: a registry-based study of the population of Sweden

PubMed Central

Westerlind, Helga; Ramanujam, Ryan; Uvehag, Daniel; Kuja-Halkola, Ralf; Boman, Marcus; Bottai, Matteo; Lichtenstein, Paul

2014-01-01

Data on familial recurrence rates of complex diseases such as multiple sclerosis give important hints to aetiological factors such as the importance of genes and environment. By linking national registries, we sought to avoid common limitations of clinic-based studies such as low numbers, poor representation of the population and selection bias. Through the Swedish Multiple Sclerosis Registry and a nationwide hospital registry, a total of 28 396 patients with multiple sclerosis were identified. We used the national Multi-Generation Registry to identify first and second degree relatives as well as cousins, and the Swedish Twin Registry to identify twins of patients with multiple sclerosis. Crude and age corrected familial risks were estimated for cases and found to be in the same range as previously published figures. Matched population-based controls were used to calculate relative risks, revealing lower estimates of familial multiple sclerosis risks than previously reported, with a sibling recurrence risk (λs = 7.1; 95% confidence interval: 6.42–7.86). Surprisingly, despite a well-established lower prevalence of multiple sclerosis amongst males, the relative risks were equal among maternal and paternal relations. A previously reported increased risk in maternal relations could thus not be replicated. An observed higher transmission rate from fathers to sons compared with mothers to sons suggested a higher transmission to offspring from the less prevalent sex; therefore, presence of the so-called ‘Carter effect’ could not be excluded. We estimated the heritability of multiple sclerosis using 74 757 twin pairs with known zygosity, of which 315 were affected with multiple sclerosis, and added information from 2.5 million sibling pairs to increase power. The heritability was estimated to be 0.64 (0.36–0.76), whereas the shared environmental component was estimated to be 0.01 (0.00–0.18). In summary, whereas multiple sclerosis is to a great extent an inherited trait, the familial relative risks may be lower than usually reported. PMID:24441172

Metabolic pathways as possible therapeutic targets for progressive multiple sclerosis.

PubMed

Heidker, Rebecca M; Emerson, Mitchell R; LeVine, Steven M

2017-08-01

Unlike relapsing remitting multiple sclerosis, there are very few therapeutic options for patients with progressive forms of multiple sclerosis. While immune mechanisms are key participants in the pathogenesis of relapsing remitting multiple sclerosis, the mechanisms underlying the development of progressive multiple sclerosis are less well understood. Putative mechanisms behind progressive multiple sclerosis have been put forth: insufficient energy production via mitochondrial dysfunction, activated microglia, iron accumulation, oxidative stress, activated astrocytes, Wallerian degeneration, apoptosis, etc . Furthermore, repair processes such as remyelination are incomplete. Experimental therapies that strive to improve metabolism within neurons and glia, e.g. , oligodendrocytes, could act to counter inadequate energy supplies and/or support remyelination. Most experimental approaches have been examined as standalone interventions; however, it is apparent that the biochemical steps being targeted are part of larger pathways, which are further intertwined with other metabolic pathways. Thus, the potential benefits of a tested intervention, or of an established therapy, e.g. , ocrelizumab, could be undermined by constraints on upstream and/or downstream steps. If correct, then this argues for a more comprehensive, multifaceted approach to therapy. Here we review experimental approaches to support neuronal and glial metabolism, and/or promote remyelination, which may have potential to lessen or delay progressive multiple sclerosis.

Gait Characteristics in Adolescents With Multiple Sclerosis.

PubMed

Kalron, Alon; Frid, Lior; Menascu, Shay

2017-03-01

Multiple sclerosis is a progressive autoimmune disease of the central nervous system. A presentation of multiple sclerosis before age18 years has traditionally been thought to be rare. However, during the past decade, more cases have been reported. We examined gait characteristics in 24 adolescents with multiple sclerosis (12 girls, 12 boys). Mean disease duration was 20.4 (S.D. = 24.9) months and mean age was 15.5 (S.D. = 1.1) years. The mean expanded disability status scale score was 1.7 (S.D. = 0.7) indicating minimal disability. Outcomes were compared with gait and the gait variability index value of healthy age-matched adolescents. Adolescents with multiple sclerosis walked slower with a wider base of support compared with age-matched healthy control subjects. Moreover, the gait variability index was lower in the multiple sclerosis group compared with the values in the healthy adolescents: 85.4 (S.D. = 8.1) versus 96.5 (S.D. = 7.4). We present gait parameters of adolescents with multiple sclerosis. From a clinical standpoint, our data could improve management of walking dysfunction in this relatively young population. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of Acupuncture on Gait of Patients with Multiple Sclerosis.

PubMed

Criado, Maria Begoña; Santos, Maria João; Machado, Jorge; Gonçalves, Arminda Manuela; Greten, Henry Johannes

2017-11-01

Multiple sclerosis is considered a complex and heterogeneous disease. Approximately 85% of patients with multiple sclerosis indicate impaired gait as one of the major limitations in their daily life. Acupuncture studies found a reduction of spasticity and improvement of fatigue and imbalance in patients with multiple sclerosis, but there is a lack of studies regarding gait. We designed a study of acupuncture treatment, according to the Heidelberg model of Traditional Chinese Medicine (TCM), to investigate if acupuncture can be a useful therapeutic strategy in patients with gait impairment in multiple sclerosis of relapsing-remitting type. The sample consisted of 20 individuals with diagnosis of multiple sclerosis of relapsing-remitting type. Gait impairment was evaluated by the 25-foot walk test. The results showed differences in time to walk 25 feet following true acupuncture. In contrast, there was no difference in time to walk 25 feet following sham acupuncture. When using true acupuncture, 95% of cases showed an improvement in 25-foot walk test, compared with 45% when sham acupuncture was done. Our study protocol provides evidence that acupuncture treatment can be an attractive option for patients with multiple sclerosis, with gait impairment.

A multigenerational family with multiple sclerosis.

PubMed

Dyment, D A; Cader, M Z; Willer, C J; Risch, N; Sadovnick, A D; Ebers, G C

2002-07-01

We report a family with 15 individuals affected with multiple sclerosis present in three and possibly four generations. The segregation of multiple sclerosis within this pedigree is consistent with an autosomal dominant mode of inheritance with reduced penetrance. The clinical characteristics of the affected individuals are indistinguishable from those seen in sporadic multiple sclerosis with respect to sex ratio, age at onset, onset symptom, MRI and clinical course. Eleven of 14 cases (78.6%) were positive for the known multiple sclerosis-associated major histocompatibility complex (MHC) Class II HLA DRB1*15 allele. Parametric linkage analysis gave a non-significant LOD score of 0.31 (theta; = 0.33) for the DRB1 gene. However, among 11 affected children with at least one DRB1*15 bearing parent, all 11 out of 11 received at least one copy of this known susceptibility allele. A transmission disequilibrium test analysis was significant for the DRB1*15 allele within this single family; P = 0.0054. The inheritance pattern in this family suggests the presence of a single major locus responsible for multiple sclerosis susceptibility, with DRB1 acting as an important modifier. This family could be an important resource for the identification of a multiple sclerosis susceptibility gene.

77 FR 23601 - Special Local Regulations and Safety Zones; Recurring Events in Northern New England

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-20

... Multiple Sclerosis Regatta......... Event Type: Regatta and Sailboat Race. Sponsor: Maine Chapter, Multiple...'' W. 8.7 Multiple Sclerosis Harborfest Event Type: Power Boat Tugboat Race. Race. Sponsor: Maine Chapter, National Multiple Sclerosis Society. Date: A one day event on Sunday during the third week of...

Factors affecting dignity of patients with multiple sclerosis.

PubMed

Sharifi, Simin; Borhani, Fariba; Abbaszadeh, Abbas

2016-12-01

MS is one of the most common chronic diseases of the nervous system. Apart from disease progression, other complications such as unemployment, separation and divorce could potentially threat patients' dignity. Most of the previous studies have been done of maintaining patients' dignity in interaction with healthcare team, but studies on affecting factors of dignity in chronic patients in the society and in interaction with usual people are scarce. We aimed to investigate factors affecting dignity of Iranian patients with MS in daily living and in interaction of them with the society. In this qualitative study, 13 patients with multiple sclerosis were chosen by purposive sampling and semi-structured interviews were conducted until data saturation. The study was done in Tehran, the capital city of Iran. Factors affecting dignity were classified as 'personal factors' and 'social factors'. Personal factors consist of the following subcategories: patients' communication with self, patients' knowledge, patients' values and beliefs and patients' resources. Social factors include others' communication with patients, social knowledge, social values and beliefs and social resources. Multiple personal and social factors interfere in perceived patient dignity. In fact, interaction between personal and social factors can be influential in final perceived dignity. By focusing on whole aspects of the patients' lives, we can identify dignity-promoting or dignity-threatening factors and help patients maintain their dignity by taking appropriate measures for moderating threatening factors and improving dignity enhancing ones. © 2016 Nordic College of Caring Science.

Diffusion Tensor Imaging as a Biomarker to Differentiate Acute Disseminated Encephalomyelitis From Multiple Sclerosis at First Demyelination.

PubMed

Aung, Wint Yan; Massoumzadeh, Parinaz; Najmi, Safa; Salter, Amber; Heaps, Jodi; Benzinger, Tammie L S; Mar, Soe

2018-01-01

There are no clinical features or biomarkers that can reliably differentiate acute disseminated encephalomyelitis from multiple sclerosis at the first demyelination attack. Consequently, a final diagnosis is sometimes delayed by months and years of follow-up. Early treatment for multiple sclerosis is recommended to reduce long-term disability. Therefore, we intend to explore neuroimaging biomarkers that can reliably distinguish between the two diagnoses. We reviewed prospectively collected clinical, standard MRI and diffusion tensor imaging data from 12 pediatric patients who presented with acute demyelination with and without encephalopathy. Patients were followed for an average of 6.5 years to determine the accuracy of final diagnosis. Final diagnosis was determined using 2013 International Pediatric MS Study Group criteria. Control subjects consisted of four age-matched healthy individuals for each patient. The study population consisted of six patients with central nervous system demyelination with encephalopathy with a presumed diagnosis of acute disseminated encephalomyelitis and six without encephalopathy with a presumed diagnosis of multiple sclerosis or clinically isolated syndrome at high risk for multiple sclerosis. During follow-up, two patients with initial diagnosis of acute disseminated encephalomyelitis were later diagnosed with multiple sclerosis. Diffusion tensor imaging region of interest analysis of baseline scans showed differences between final diagnosis of multiple sclerosis and acute disseminated encephalomyelitis patients, whereby low fractional anisotropy and high radial diffusivity occurred in multiple sclerosis patients compared with acute disseminated encephalomyelitis patients and the age-matched controls. Fractional anisotropy and radial diffusivity measures may have the potential to serve as biomarkers for distinguishing acute disseminated encephalomyelitis from multiple sclerosis at the onset. Copyright © 2017 Elsevier Inc. All rights reserved.

Physical Activity and Its Correlates in Youth with Multiple Sclerosis.

PubMed

Grover, Stephanie A; Sawicki, Carolyn P; Kinnett-Hopkins, Dominique; Finlayson, Marcia; Schneiderman, Jane E; Banwell, Brenda; Till, Christine; Motl, Robert W; Yeh, E Ann

2016-12-01

To investigate physical activity levels in youth with multiple sclerosis and monophasic acquired demyelinating syndromes ([mono-ADS], ie, children without relapsing disease) compared with healthy controls and to determine factors that contribute to engagement in physical activity. We hypothesized that greater physical activity goal setting and physical activity self-efficacy would be associated with greater levels of vigorous physical activity in youth with multiple sclerosis. A total of 68 consecutive patients (27 multiple sclerosis, 41 mono-ADS) and 37 healthy controls completed fatigue, depression, Physical Activity Self-Efficacy Scale, perceived disability, Exercise Goal-Setting scale, and physical activity questionnaires, and wore an accelerometer for 7 days. All patients had no ambulatory limitations (Expanded Disability Status Scale, scores all <4). Youth with multiple sclerosis engaged in fewer minutes per day of vigorous (P = .009) and moderate and vigorous physical activity (P = .048) than did patients with mono-ADS and healthy controls. A lower proportion of the group with multiple sclerosis (63%) reported participating in any strenuous physical activity than the mono-ADS (85%) and healthy control (89%) groups (P = .020). When we adjusted for age and sex, the Physical Activity Self-Efficacy Scale and Exercise Goal-Setting scale were associated positively with vigorous physical activity in the group with multiple sclerosis. Fatigue and depression did not predict physical activity or accelerometry metrics. Youth with multiple sclerosis participate in less physical activity than their counterparts with mono-ADS and healthy controls. Physical activity self-efficacy and exercise goal setting serve as potentially modifiable correlates of physical activity, and are measures suited to future interventions aimed to increase physical activity in youth with multiple sclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives

PubMed Central

Ontaneda, Daniel; Fox, Robert J.; Chataway, Jeremy

2015-01-01

Progressive multiple sclerosis is characterized by the gradual accrual of disability independent of relapses and can occur with disease onset (primary progressive) or preceded by a relapsing disease course (secondary progressive). An effective disease modifying treatment for progressive multiple sclerosis has not been identified, and the results of clinical trials to date have been generally disappointing. Ongoing advances in our understanding of pathogenesis, identification of novel targets for neuro-protection, and improved outcome measures have the potential to lead to effective treatments for progressive multiple sclerosis. In this review lessons learned from previous clinical trials and perspectives from current trials in progressive multiple sclerosis are summarized. Promising clinical, imaging, and biological markers will also be reviewed, along with novel clinical trial designs. PMID:25772899

Efficacy of aquatic therapy for multiple sclerosis: a systematic review.

PubMed

Corvillo, Iluminada; Varela, Enrique; Armijo, Francisco; Alvarez-Badillo, Antonio; Armijo, Onica; Maraver, Francisco

2017-12-01

Multiple sclerosis (MS) is a chronic, inflammatory, progressive, disabling autoimmune disease affecting the central nervous system. Symptoms and signs of MS vary widely and patients may lose their ability to walk. To date the benefits of aquatic therapy often used for rehabilitation in MS patients have not been reviewed. The aim of this study was to systematically review the current state of aquatic treatment for persons with MS (hydrotherapy, aquatic therapy, aquatic exercises, spa therapy) and to evaluate the scientific evidence supporting the benefits of this therapeutic option. The databases PubMed, Scopus, WoS and PEDro were searched to identify relevant reports published from January 1, 2011 to April 30, 2016. Of 306 articles identified, only 10 fulfilled the inclusion criteria: 5 randomized controlled, 2 simple randomized quasi-experimental, 1 semi-experimental, 1 blind controlled pilot and 1 pilot. Evidence that aquatic treatment improves quality of life in affected patients was very good in two studies, good in four, fair in two and weak in two.

Conflicting Role of Mycobacterium Species in Multiple Sclerosis

PubMed Central

Cossu, Davide; Yokoyama, Kazumasa; Hattori, Nobutaka

2017-01-01

Mycobacterium is a genus of aerobic and acid-fast bacteria, which include several pathogenic organisms that cause serious diseases in mammals. Previous studies have associated the immune response against mycobacteria with multiple sclerosis (MS), a chronic demyelinating disease of the central nervous system with unknown etiology. The role of mycobacteria in the pathological process has been controversial and often conflicting. We provide a detailed review of the mycobacteria that have been linked to MS over the last three decades, with a focus on Mycobacterium bovis bacille Calmette–Guérin vaccine for human and oral exposure to Mycobacterium avium subsp. paratuberculosis. We will also discuss the exposure and genetic susceptibility to mycobacterial infection, the protective role of vaccination, as well as the possible mechanisms involved in initiating or worsening MS symptoms, with particular emphasis on the molecular mimicry between mycobacterial and human proteins. Finally, we will introduce topics such as heat shock proteins and recognition by innate immunity, and toll-like receptor signaling-mediated responses to Mycobacterium exposure. PMID:28579973

Involvement of peripheral III nerve in multiple sclerosis patient: Report of a new case and discussion of the underlying mechanism.

PubMed

Shor, Natalia; Amador, Maria Del Mar; Dormont, Didier; Lubetzki, Catherine; Bertrand, Anne

2017-04-01

Multiple sclerosis (MS) is a chronic disorder that affects the central nervous system myelin. However, a few radiological cases have documented an involvement of peripheral cranial nerves, within the subarachnoid space, in MS patients. We report the case of a 36-year-old female with a history of relapsing-remitting (RR) MS who consulted for a subacute complete paralysis of the right III nerve. Magnetic resonance imaging (MRI) examination showed enhancement and thickening of the cisternal right III nerve, in continuity with a linear, mesencephalic, acute demyelinating lesion. Radiological involvement of the cisternal part of III nerve has been reported only once in MS patients. Radiological involvement of the cisternal part of V nerve occurs more frequently, in almost 3% of MS patients. In both situations, the presence of a central demyelinating lesion, in continuity with the enhancement of the peripheral nerve, suggests that peripheral nerve damage is a secondary process, rather than a primary target of demyelination.

Combined cannabinoid therapy via an oromucosal spray.

PubMed

Perez, Jordi

2006-08-01

Extensive basic science research has identified the potential therapeutic benefits of active compounds extracted from the Cannabis sativa L. plant (the cannabinoids). It is recognized that a significant proportion of patients suffering with the debilitating symptoms of pain and spasticity in multiple sclerosis or other conditions smoke cannabis despite the legal implications and stigma associated with this controlled substance. GW Pharmaceuticals have developed Sativex (GW- 1,000-02), a combined cannabinoid medicine that delivers and maintains therapeutic levels of two principal cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), via an oromucosal pump spray, that aims to minimize psychotropic side effects. Sativex has proved to be well tolerated and successfully self-administered and self-titrated in both healthy volunteers and patient cohorts. Clinical assessment of this combined cannabinoid medicine has demonstrated efficacy in patients with intractable pain (chronic neuropathic pain, pain due to brachial plexus nerve injury, allodynic peripheral neuropathic pain and advanced cancer pain), rheumatoid arthritis and multiple sclerosis (bladder problems, spasticity and central pain), with no significant intoxication-like symptoms, tolerance or withdrawal syndrome.

Exercise and multiple sclerosis: physiological, psychological, and quality of life issues.

PubMed

Sutherland, G; Andersen, M B

2001-12-01

The case for the benefits of physical activity has been well documented in healthy individuals, and the potential for reducing the risk of mental and physical ill health is substantial. Yet, individuals with multiple sclerosis (MS) have long been advised to avoid participation in exercise in order to minimise the risk of exacerbations and symptoms of fatigue. There is, however, increasing interest in how acute and chronic exercise affect physiological and psychological functioning in MS. Much of the research has examined physiological tolerance to exercise and focused on responses in terms of heart rate, blood pressure, cardiorespiratory fitness, muscle function, and symptom stability. Little research has focused on understanding how exercise affects psychosocial functioning and brings about changes in depression, affect, mood, well-being, and quality of life. This paper provides a summary of the research exploring the efficacy of physical activity for people with MS. In addition, the key issues that face clinical practice are examined, and considerations for research are discussed.

An exploratory study on emotion recognition in patients with a clinically isolated syndrome and multiple sclerosis.

PubMed

Jehna, Margit; Neuper, Christa; Petrovic, Katja; Wallner-Blazek, Mirja; Schmidt, Reinhold; Fuchs, Siegrid; Fazekas, Franz; Enzinger, Christian

2010-07-01

Multiple sclerosis (MS) is a chronic multifocal CNS disorder which can affect higher order cognitive processes. Whereas cognitive disturbances in MS are increasingly better characterised, emotional facial expression (EFE) has rarely been tested, despite its importance for adequate social behaviour. We tested 20 patients with a clinically isolated syndrome suggestive of MS (CIS) or MS and 23 healthy controls (HC) for the ability to differ between emotional facial stimuli, controlling for the influence of depressive mood (ADS-L). We screened for cognitive dysfunction using The Faces Symbol Test (FST). The patients demonstrated significant decreased reaction-times regarding emotion recognition tests compared to HC. However, the results also suggested worse cognitive abilities in the patients. Emotional and cognitive test results were correlated. This exploratory pilot study suggests that emotion recognition deficits might be prevalent in MS. However, future studies will be needed to overcome the limitations of this study. Copyright 2010 Elsevier B.V. All rights reserved.

Teriflunomide for the treatment of relapsing-remitting multiple sclerosis: patient preference and adherence.

PubMed

Bayas, Antonios; Mäurer, Mathias

2015-01-01

Multiple sclerosis (MS), a chronic demyelinating neuroinflammatory disease of the central nervous system, is the most common neurological disorder leading to disability in young adulthood. In the last 2 decades, numerous treatments for relapsing-remitting MS have been approved with eleven treatment options available worldwide. One of the determinants in treatment selection is disease activity in the individual patient. However, patient preferences play an increasingly major role in treatment decision making. With teriflunomide, a reversible inhibitor of the enzyme dihydroorotate dehydrogenase, a new oral therapeutic option, given once daily, has been approved within the last 2 years by the regulatory agencies. The current review focuses on characteristics of the drug relevant for patients' preferences in the treatment decision process in the light of the available medications. Perceiving and considering patients' preferences will have an effect on treatment adherence, which is known to be often low in MS patients. Teriflunomide-related adherence issues will also be discussed regarding mode of application, dosing, and potential side effects.

The "Gut Feeling": Breaking Down the Role of Gut Microbiome in Multiple Sclerosis.

PubMed

Freedman, Samantha N; Shahi, Shailesh K; Mangalam, Ashutosh K

2018-01-01

Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system with unknown etiology. Recently, the gut microbiota has emerged as a potential factor in the development of MS, with a number of studies having shown that patients with MS exhibit gut dysbiosis. The gut microbiota helps the host remain healthy by regulating various functions, including food metabolism, energy homeostasis, maintenance of the intestinal barrier, inhibition of colonization by pathogenic organisms, and shaping of both mucosal and systemic immune responses. Alteration of the gut microbiota, and subsequent changes in its metabolic network that perturb this homeostasis, may lead to intestinal and systemic disorders such as MS. Here we discuss the findings of recent MS microbiome studies and potential mechanisms through which gut microbiota can predispose to, or protect against, MS. These findings highlight the need of an improved understanding of the interactions between the microbiota and host for developing therapies based on gut commensals with which to treat MS.

detecting multiple sclerosis lesions with a fully bioinspired visual attention model

NASA Astrophysics Data System (ADS)

Villalon-Reina, Julio; Gutierrez-Carvajal, Ricardo; Thompson, Paul M.; Romero-Castro, Eduardo

2013-11-01

The detection, segmentation and quantification of multiple sclerosis (MS) lesions on magnetic resonance images (MRI) has been a very active field for the last two decades because of the urge to correlate these measures with the effectiveness of pharmacological treatment. A myriad of methods has been developed and most of these are non specific for the type of lesions and segment the lesions in their acute and chronic phases together. On the other hand, radiologists are able to distinguish between several stages of the disease on different types of MRI images. The main motivation of the work presented here is to computationally emulate the visual perception of the radiologist by using modeling principles of the neuronal centers along the visual system. By using this approach we are able to detect the lesions in the majority of the images in our population sample. This type of approach also allows us to study and improve the analysis of brain networks by introducing a priori information.

Effect of physical exercise on brain and lipid metabolism in mouse models of multiple sclerosis.

PubMed

Houdebine, Léo; Gallelli, Cristina Anna; Rastelli, Marialetizia; Sampathkumar, Nirmal Kumar; Grenier, Julien

2017-10-01

Multiple sclerosis (MS) is a central nervous demyelinating disease characterized by cyclic loss and repair of myelin sheaths associated with chronic inflammation and neuronal loss. This degenerative pathology is accompanied by modified levels of oxysterols (oxidative derivatives of cholesterol, implicated in cholesterol metabolism), highlighted in the brain, blood and cerebrospinal fluid of MS patients. The pathological accumulation of such derivatives is thought to participate in the onset and progression of the disease through their implication in inflammation, oxidative stress, demyelination and neurodegeneration. In this context, physical exercise is envisaged as a complementary resource to ameliorate therapeutic strategies. Indeed, physical activity exerts beneficial effects on neuronal plasticity, decreases inflammation and oxidative stress and improves blood-brain integrity in extents that could be beneficial for brain health. The present review attempts to summarize the available data on the positive effect of physical exercise to highlight possible links between physical activity and modulation of cholesterol/oxysterol homeostasis in MS. Copyright © 2017 Elsevier B.V. All rights reserved.

Management of multiple sclerosis: the role of coping self-efficacy and self-esteem.

PubMed

Mikula, Pavol; Nagyova, Iveta; Vitkova, Marianna; Szilasiova, Jarmila

2018-02-07

Patients with multiple sclerosis (MS) engage in various coping behaviours in order to manage their disease. The aim of this study is to find out if the self-esteem of patients is associated with coping strategies - problem-focused (e.g. making a plan of action when confronted with a problem); emotion focused (e.g. get emotional support from community); and focused on stopping unpleasant emotions and thoughts (e.g. keeping oneself from feeling sad), and if it can enhance or hinder coping efforts in the disease management. We collected data from 155 consecutive MS patients who completed the Coping Self-Efficacy Scale (CSE) and the Rosenberg Self-esteem Scale (RSE). Explained variance for problem-focused coping, emotion-focused coping, and coping focused on stopping unpleasant emotions and thoughts was 33, 24, and 31%, respectively. Self-esteem seems to be associated with coping strategies indicating that feelings of self-worth are linked with the ability to handle difficult life situations and can be helpful in chronic disease management.

Adverse Childhood Experiences Are Linked to Age of Onset and Reading Recognition in Multiple Sclerosis.

PubMed

Shaw, Michael T; Pawlak, Natalie O; Frontario, Ariana; Sherman, Kathleen; Krupp, Lauren B; Charvet, Leigh E

2017-01-01

Adverse childhood experiences (ACEs) exert a psychological and physiological toll that increases risk of chronic conditions, poorer social functioning, and cognitive impairment in adulthood. To investigate the relationship between childhood adversity and clinical disease features in multiple sclerosis (MS). Sixty-seven participants with MS completed the ACE assessment and neuropsychological assessments as part of a larger clinical trial of cognitive remediation. Adverse childhood experience scores, a measure of exposure to adverse events in childhood, significantly predicted age of MS onset ( r  = -0.30, p  = 0.04). ACEs were also linked to reading recognition (a proxy for premorbid IQ) ( r  = -0.25, p  = 0.04). ACE scores were not related to age, current disability, or current level of cognitive impairment measured by the Symbol Digit Modalities Test (SDMT). Childhood adversity may increase the likelihood of earlier age of onset and poorer estimated premorbid IQ in MS.

The Essential Role of Epstein-Barr Virus in the Pathogenesis of Multiple Sclerosis

PubMed Central

Pender, Michael P.

2011-01-01

There is increasing evidence that infection with the Epstein-Barr virus (EBV) plays a role in the development of multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the CNS. This article provides a four-tier hypothesis proposing (1) EBV infection is essential for the development of MS; (2) EBV causes MS in genetically susceptible individuals by infecting autoreactive B cells, which seed the CNS where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells that would otherwise die in the CNS by apoptosis; (3) the susceptibility to develop MS after EBV infection is dependent on a genetically determined quantitative deficiency of the cytotoxic CD8+ T cells that normally keep EBV infection under tight control; and (4) sunlight and vitamin D protect against MS by increasing the number of CD8+ T cells available to control EBV infection. The hypothesis makes predictions that can be tested, including the prevention and successful treatment of MS by controlling EBV infection. PMID:21075971

[Current aspects of therapy conversion for multiple sclerosis].

PubMed

Kolber, P; Luessi, F; Meuth, S G; Klotz, L; Korn, T; Trebst, C; Tackenberg, B; Kieseier, B; Kümpfel, T; Fleischer, V; Tumani, H; Wildemann, B; Lang, M; Flachenecker, P; Meier, U; Brück, W; Limmroth, V; Haghikia, A; Hartung, H-P; Stangel, M; Hohlfeld, R; Hemmer, B; Gold, R; Wiendl, H; Zipp, F

2015-10-01

In recent years the approval of new substances has led to a substantial increase in the number of course-modifying immunotherapies available for multiple sclerosis. Therapy conversion therefore represents an increasing challenge. The treatment options sometimes show complex adverse effect profiles and necessitate a long-term and comprehensive monitoring. This article presents an overview of therapy conversion of immunotherapies for multiple sclerosis in accordance with the recommendations of the Disease-Related Competence Network for Multiple Sclerosis and the German Multiple Sclerosis Society as well as the guidelines on diagnostics and therapy for multiple sclerosis of the German Society of Neurology and the latest research results. At the present point in time it should be noted that no studies have been carried out for most of the approaches for therapy conversion given here; however, the recommendations are based on theoretical considerations and therefore correspond to recommendations at the level of expert consensus, which is currently essential for the clinical daily routine.

Nurse-led immunotreatment DEcision Coaching In people with Multiple Sclerosis (DECIMS) - Feasibility testing, pilot randomised controlled trial and mixed methods process evaluation.

PubMed

Rahn, A C; Köpke, S; Backhus, I; Kasper, J; Anger, K; Untiedt, B; Alegiani, A; Kleiter, I; Mühlhauser, I; Heesen, C

2018-02-01

Treatment decision-making is complex for people with multiple sclerosis. Profound information on available options is virtually not possible in regular neurologist encounters. The "nurse decision coach model" was developed to redistribute health professionals' tasks in supporting immunotreatment decision-making following the principles of informed shared decision-making. To test the feasibility of a decision coaching programme and recruitment strategies to inform the main trial. Feasibility testing and parallel pilot randomised controlled trial, accompanied by a mixed methods process evaluation. Two German multiple sclerosis university centres. People with suspected or relapsing-remitting multiple sclerosis facing immunotreatment decisions on first line drugs were recruited. Randomisation to the intervention (n = 38) or control group (n = 35) was performed on a daily basis. Quantitative and qualitative process data were collected from people with multiple sclerosis, nurses and physicians. We report on the development and piloting of the decision coaching programme. It comprises a training course for multiple sclerosis nurses and the coaching intervention. The intervention consists of up to three structured nurse-led decision coaching sessions, access to an evidence-based online information platform (DECIMS-Wiki) and a final physician consultation. After feasibility testing, a pilot randomised controlled trial was performed. People with multiple sclerosis were randomised to the intervention or control group. The latter had also access to the DECIMS-Wiki, but received otherwise care as usual. Nurses were not blinded to group assignment, while people with multiple sclerosis and physicians were. The primary outcome was 'informed choice' after six months including the sub-dimensions' risk knowledge (after 14 days), attitude concerning immunotreatment (after physician consultation), and treatment uptake (after six months). Quantitative process evaluation data were collected via questionnaires. Qualitative interviews were performed with all nurses and a convenience sample of nine people with multiple sclerosis. 116 people with multiple sclerosis fulfilled the inclusion criteria and 73 (63%) were included. Groups were comparable at baseline. Data of 51 people with multiple sclerosis (70%) were available for the primary endpoint. In the intervention group 15 of 31 (48%) people with multiple sclerosis achieved an informed choice after six months and 6 of 20 (30%) in the control group. Process evaluation data illustrated a positive response towards the coaching programme as well as good acceptance. The pilot-phase showed promising results concerning acceptability and feasibility of the intervention, which was well perceived by people with multiple sclerosis, most nurses and physicians. Delegating parts of the immunotreatment decision-making process to trained nurses has the potential to increase informed choice and participation as well as effectiveness of patient-physician consultations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human placenta-derived cells (PDA-001) for the treatment of adults with multiple sclerosis: a randomized, placebo-controlled, multiple-dose study.

PubMed

Lublin, Fred D; Bowen, James D; Huddlestone, John; Kremenchutzky, Marcelo; Carpenter, Adam; Corboy, John R; Freedman, Mark S; Krupp, Lauren; Paulo, Corri; Hariri, Robert J; Fischkoff, Steven A

2014-11-01

Infusion of PDA-001, a preparation of mesenchymal-like cells derived from full-term human placenta, is a new approach in the treatment of patients with multiple sclerosis. This safety study aimed to rule out the possibility of paradoxical exacerbation of disease activity by PDA-001 in patients with multiple sclerosis. This was a phase 1b, multicenter, randomized, double-blind, placebo-controlled, 2-dose ranging study including patients with relapsing-remitting multiple sclerosis or secondary progressive multiple sclerosis. The study was conducted at 6 sites in the United States and 2 sites in Canada. Patients were randomized 3:1 to receive 2 low-dose infusions of PDA-001 (150×10(6) cells) or placebo, given 1 week apart. After completing this cohort, subsequent patients received high-dose PDA-001 (600×10(6) cells) or placebo. Monthly brain magnetic resonance imaging scans were performed. The primary end point was ruling out the possibility of paradoxical worsening of MS disease activity. This was monitored using Cutter׳s rule (≥5 new gadolinium lesions on 2 consecutive scans) by brain magnetic resonance imaging on a monthly basis for six months and also the frequency of multiple sclerosis relapse. Ten patients with relapsing-remitting multiple sclerosis and 6 with secondary progressive multiple sclerosis were randomly assigned to treatment: 6 to low-dose PDA-001, 6 to high-dose PDA-001, and 4 to placebo. No patient met Cutter׳s rule. One patient receiving high-dose PDA-001 had an increase in T2 and gadolinium lesions and in Expanded Disability Status Scale score during a multiple sclerosis flare 5 months after receiving PDA-001. No other patient had an increase in Expanded Disability Status Scale score>0.5, and most had stable or decreasing Expanded Disability Status Scale scores. With high-dose PDA-001, 1 patient experienced a grade 1 anaphylactoid reaction and 1 had grade 2 superficial thrombophlebitis. Other adverse events were mild to moderate and included headache, fatigue, infusion site reactions, and urinary tract infection. PDA-001 infusions were safe and well tolerated in relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis patients. No paradoxical worsening of lesion counts was noted with either dose. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Immunomodulatory Role of Diet and Adipokines in Multiple Sclerosis and Its Animal Model

DTIC Science & Technology

2015-09-01

beginning to be elucidated. In this regard, MS has been studied very little. Several recent studies showed that obesity during childhood /young adulthood...confers increased risk of developing MS. Obesity in the past 20 years has become an epidemic in western counties. New evidence suggests a link...between obesity and several autoimmune diseases (Procaccini, Carbone et al. 2011). Obesity is characterized by a low-grade chronic inflammatory state

Diagnosis and treatment of latent tuberculosis in patients with multiple sclerosis, expert consensus. On behalf of the Colombian Association of Neurology, Committee of Multiple Sclerosis.

PubMed

Navas, Carlos; Torres-Duque, Carlos A; Munoz-Ceron, Joe; Álvarez, Carlos; García, Juan R; Zarco, Luis; Vélez, Lázaro A; Awad, Carlos; Castro, Carlos Alberto

2018-01-01

Multiple sclerosis is an inflammatory and neurodegenerative demyelinating disease. Current treatment of multiple sclerosis focuses on the use of immunomodulatory, immunosuppressant, and selective immunosuppressant agents. Some of these medications may result in high risk of opportunistic infections including tuberculosis. The purpose of this study was to obtain consensus from a panel of neurologists, pulmonologists, infectious disease specialists, and epidemiology experts regarding the diagnosis, treatment, and monitoring of latent tuberculosis in patients with multiple sclerosis. A panel of experts in multiple sclerosis and tuberculosis was established. The methodological process was performed in three phases: definition of questions, answer using Delphi methodology, and the discussion of questions not agreed. Tuberculosis screening is suggested when multiple sclerosis drugs are prescribed. The recommended tests for latent tuberculosis are tuberculin and interferon gamma release test. When an anti-tuberculosis treatment is indicated, monitoring should be performed to determine liver enzyme values with consideration of age as well as comorbid conditions such as a history of alcoholism, age, obesity, concomitant hepatotoxic drugs, and history of liver disease. Latent tuberculosis should be considered in patients with multiple sclerosis who are going to be treated with immunomodulatory and immunosuppressant medications. Transaminase level monitoring is required on a periodic basis depending on clinical and laboratory characteristics. In addition to the liver impairment, other side effects should be considered when Isoniazid is prescribed.

[Effect of preventive treatment on cognitive performance in patients with multiple sclerosis].

PubMed

Shorobura, Maria S

2018-01-01

Introduction: cognitive, emotional and psychopathological changes play a significant role in the clinical picture of multiple sclerosis and influence the effectiveness of drug therapy, working capacity, quality of life, and the process of rehabilitation of patients with multiple sclerosis. The aim: investigate the changes in cognitive function in patients with multiple sclerosis, such as information processing speed and working memory of patients before and after treatment with immunomodulating drug. Materials and methods:33 patients examined reliably diagnosed with multiple sclerosis who were treated with preventive examinations and treatment from 2012 to 2016. For all patients with multiple sclerosis had clinical-neurological examination (neurological status using the EDSS scale) and the cognitive status was evaluated using the PASAT auditory test. Patient screening was performed before, during and after the therapy. Statistical analysis of the results was performed in the system Statistica 8.0. We used Student's t-test (t), Mann-Whitney test (Z). Person evaluated the correlation coefficients and Spearman (r, R), Wilcoxon criterion (T), Chi-square (X²). Results: The age of patients with multiple sclerosis affects the growth and EDSS scale score decrease PASAT to treatment. Duration of illness affects the EDSS scale score and performance PASAT. Indicators PASAT not significantly decreased throughout the treatment. Conclusions: glatiramer acetate has a positive effect on cognitive function, information processing speed and working memory patients with multiple sclerosis, which is one of the important components of the therapeutic effect of this drug.

Surveillance and medical therapy following endovascular treatment of chronic cerebrospinal venous insufficiency.

PubMed

Forbes, Thomas L; Harris, Jeremy R; Kribs, Stewart W

2012-06-01

The debate regarding the possible link between chronic cerebrospinal venous insufficiency and multiple sclerosis (MS) is continuously becoming more and more contentious due to the current lack of level 1 evidence from randomized trials. Regardless of this continued uncertainty surrounding the safety and efficacy of this therapy, MS patients from Canada, and other jurisdictions, are traveling abroad to receive central venous angioplasty and, unfortunately, some also receive venous stents. They often return home with few instructions regarding follow-up or medical therapy. In response we propose some interim, practical recommendations for post-procedural surveillance and medical therapy, until further information is available.

Multiple sclerosis and human T-cell lymphotropic retroviruses

NASA Astrophysics Data System (ADS)

Koprowski, Hilary; Defreitas, Elaine C.; Harper, Mary E.; Sandberg-Wollheim, Magnhild; Sheremata, William A.; Robert-Guroff, Marjorie; Saxinger, Carl W.; Feinberg, Mark B.; Wong-Staal, Flossie; Gallo, Robert C.

1985-11-01

A combination of different types of data suggests that some multiple sclerosis patients respond immunologically to, and have cerebrospinal T cells containing, a retrovirus that is related to, but distinct from, the three types of human T-cell lymphotropic viruses. The role of this virus in multiple sclerosis is uncertain.

Disconnection as a Mechanism for Cognitive Dysfunction in Multiple Sclerosis

ERIC Educational Resources Information Center

Dineen, R. A.; Vilisaar, J.; Hlinka, J.; Bradshaw, C. M.; Morgan, P. S.; Constantinescu, C. S.; Auer, D. P.

2009-01-01

Disconnection of cognitively important processing regions by injury to the interconnecting white matter provides a potential mechanism for cognitive dysfunction in multiple sclerosis. The contribution of tract-specific white matter injury to dysfunction in different cognitive domains in patients with multiple sclerosis has not previously been…

Demyelination of subcortical nuclei in multiple sclerosis

NASA Astrophysics Data System (ADS)

Krutenkova, E.; Aitmagambetova, G.; Khodanovich, M.; Bowen, J.; Gangadharan, B.; Henson, L.; Mayadev, A.; Repovic, P.; Qian, P.; Yarnykh, V.

2016-02-01

Myelin containing in basal ganglia in multiple sclerosis patients was evaluated using new noninvasive quantitative MRI method fast whole brain macromolecular proton fraction mapping. Myelin level in globus pallidus and putamen significantly decreased in multiple sclerosis patients as compared with healthy control subjects but not in substantia nigra and caudate nucleus.

Multiple Sclerosis and the Family Physician

PubMed Central

Sky, Ruth

1977-01-01

Multiple sclerosis is difficult to diagnose since it develops over a period of time and the symptoms and signs are scattered throughout the central nervous system. Because there is no specific treatment, the problems of management are especially challenging. Case histories are presented to support the concept that multiple sclerosis is a family and community concern. Family physicians are urged to maintain a supportive role and an interested attitude towards patients with multiple sclerosis. These patients and their families have urgent and continuing needs for their doctors' skills. PMID:21304869

Novel Insights and Therapeutics in Multiple Sclerosis.

PubMed

Wagner, Catriona A; Goverman, Joan M

2015-01-01

The last twelve years have witnessed the development of new therapies for relapsing-remitting multiple sclerosis that demonstrate increased efficacy relative to previous therapies. Many of these new drugs target the inflammatory phase of disease by manipulating different aspects of the immune system. While these new treatments are promising, the development of therapies for patients with progressive multiple sclerosis remains a significant challenge. We discuss the distinct mechanisms that may contribute to these two types of multiple sclerosis and the implications of these differences in the development of new therapeutic targets for this debilitating disease.

Antecedents of Coping with the Disease in Patients with Multiple Sclerosis: A Qualitative Content Analysis

PubMed Central

Dehghani, Ali; Dehghan Nayeri, Nahid; Ebadi, Abbas

2017-01-01

ABSTRACT Background: Due to many physical and mental disorders that occur in multiple sclerosis patients, identifying the factors affecting coping based on the experiences of patients using qualitative study is essential to improve their quality of life. This study was conducted to explore the antecedents of coping with the disease in patients with multiple sclerosis. Methods: This is a qualitative study conducted on 11 patients with multiple sclerosis in 2015 in Tehran, Iran. These patients were selected based on purposive sampling. Data were collected using semi-structured and in-depth interviews and coded. These data were analyzed using the conventional content analysis. The rigor of qualitative data using the criteria proposed by Guba and Lincoln were assessed. Results: Five main categories were revealed: (1) social support, (2) lenience, (3) reliance on faith, (4) knowledge of multiple sclerosis and modeling, and (5) economic and environmental situation. Each category had several distinct sub-categories. Conclusions: The results of this study showed that coping with multiple sclerosis is a complex, multidimensional and contextual concept that is affected by various factors in relation to the context of Iran. The findings of the study can provide the healthcare professionals with deeper recognition and understanding of these antecedents to improve successful coping in Iranian patients suffering from multiple sclerosis. PMID:28097178

'Normal' and 'failing' mothers: Women's constructions of maternal subjectivity while living with multiple sclerosis.

PubMed

Parton, Chloe; Katz, Terri; Ussher, Jane M

2017-10-01

Multiple sclerosis causes physical and cognitive impairment that can impact women's experiences of motherhood. This study examined how women construct their maternal subjectivities, or sense of self as a mother, drawing on a framework of biographical disruption. A total of 20 mothers with a multiple sclerosis diagnosis took part in semi-structured interviews. Transcripts were analysed using thematic decomposition to identify subject positions that women adopted in relation to cultural discourses of gender, motherhood and illness. Three main subject positions were identified: 'The Failing Mother', 'Fear of Judgement and Burdening Others' and 'The Normal Mother'. Women's sense of self as the 'Failing Mother' was attributed to the impact of multiple sclerosis, contributing to biographical disruption and reinforced through 'Fear of Judgement and Burdening Others' within social interactions. In accounts of the 'Normal Mother', maternal subjectivity was renegotiated by adopting strategies to manage the limitations of multiple sclerosis on mothering practice. This allowed women to self-position as 'good' mothers. Health professionals can assist women by acknowledging the embodied impact of multiple sclerosis on maternal subjectivities, coping strategies that women employ to address potential biographical disruption, and the cultural context of mothering, which contributes to women's experience of subjectivity and well-being when living with multiple sclerosis.

Visual Search as a Tool for a Quick and Reliable Assessment of Cognitive Functions in Patients with Multiple Sclerosis

PubMed Central

Utz, Kathrin S.; Hankeln, Thomas M. A.; Jung, Lena; Lämmer, Alexandra; Waschbisch, Anne; Lee, De-Hyung; Linker, Ralf A.; Schenk, Thomas

2013-01-01

Background Despite the high frequency of cognitive impairment in multiple sclerosis, its assessment has not gained entrance into clinical routine yet, due to lack of time-saving and suitable tests for patients with multiple sclerosis. Objective The aim of the study was to compare the paradigm of visual search with neuropsychological standard tests, in order to identify the test that discriminates best between patients with multiple sclerosis and healthy individuals concerning cognitive functions, without being susceptible to practice effects. Methods Patients with relapsing remitting multiple sclerosis (n = 38) and age-and gender-matched healthy individuals (n = 40) were tested with common neuropsychological tests and a computer-based visual search task, whereby a target stimulus has to be detected amongst distracting stimuli on a touch screen. Twenty-eight of the healthy individuals were re-tested in order to determine potential practice effects. Results Mean reaction time reflecting visual attention and movement time indicating motor execution in the visual search task discriminated best between healthy individuals and patients with multiple sclerosis, without practice effects. Conclusions Visual search is a promising instrument for the assessment of cognitive functions and potentially cognitive changes in patients with multiple sclerosis thanks to its good discriminatory power and insusceptibility to practice effects. PMID:24282604

Efficacy of Fish Oil on Serum of TNFα, IL-1β, and IL-6 Oxidative Stress Markers in Multiple Sclerosis Treated with Interferon Beta-1b

PubMed Central

Ramirez-Ramirez, V.; Macias-Islas, M. A.; Ortiz, G. G.; Pacheco-Moises, F.; Torres-Sanchez, E. D.; Sorto-Gomez, T. E.; Cruz-Ramos, J. A.; Orozco-Aviña, G.; Celis de la Rosa, A. J.

2013-01-01

Multiple sclerosis (MS) is a chronic inflammatory disease, which leads to focal plaques of demyelination and tissue injury in the central nervous system. Oxidative stress is also thought to promote tissue damage in multiple sclerosis. Current research findings suggest that omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapenta-enoic acid (EPA) and docosahexaenoic acid (DHA) contained in fish oil may have anti-inflammatory, antioxidant, and neuroprotective effects. The aim of the present work was to evaluate the efficacy of fish oil supplementation on serum proinflammatory cytokine levels, oxidative stress markers, and disease progression in MS. 50 patients with relapsing-remitting MS were enrolled. The experimental group received orally 4 g/day of fish oil for 12 months. The primary outcome was serum TNFα levels; secondary outcomes were IL-1β 1b, IL-6, nitric oxide catabolites, lipoperoxides, progression on the expanded disability status scale (EDSS), and annualized relapses rate (ARR). Fish oil treatment decreased the serum levels of TNFα, IL-1β, IL-6, and nitric oxide metabolites compared with placebo group (P ≤ 0.001). There was no significant difference in serum lipoperoxide levels during the study. No differences in EDSS and ARR were found. Conclusion. Fish oil supplementation is highly effective in reducing the levels of cytokines and nitric oxide catabolites in patients with relapsing-remitting MS. PMID:23861993

Electromagnetic hypersensitivity: biological effects of dirty electricity with emphasis on diabetes and multiple sclerosis.

PubMed

Havas, Magda

2006-01-01

Dirty electricity is a ubiquitous pollutant. It flows along wires and radiates from them and involves both extremely low frequency electromagnetic fields and radio frequency radiation. Until recently, dirty electricity has been largely ignored by the scientific community. Recent inventions of metering and filter equipment provide scientists with the tools to measure and reduce dirty electricity on electrical wires. Several case studies and anecdotal reports are presented. Graham/Stetzer (GS) filters have been installed in schools with sick building syndrome and both staff and students reported improved health and more energy. The number of students needing inhalers for asthma was reduced in one school and student behavior associated with ADD/ADHD improved in another school. Blood sugar levels for some diabetics respond to the amount of dirty electricity in their environment. Type 1 diabetics require less insulin and Type 2 diabetics have lower blood sugar levels in an electromagnetically clean environment. Individuals diagnosed with multiple sclerosis have better balance and fewer tremors. Those requiring a cane walked unassisted within a few days to weeks after GS filters were installed in their home. Several disorders, including asthma, ADD/ADHD, diabetes, multiple sclerosis, chronic fatigue, fibromyalgia, are increasing at an alarming rate, as is electromagnetic pollution in the form of dirty electricity, ground current, and radio frequency radiation from wireless devices. The connection between electromagnetic pollution and these disorders needs to be investigated and the percentage of people sensitive to this form of energy needs to be determined.

Effects of education level and employment status on HRQoL in early relapsing-remitting multiple sclerosis.

PubMed

Patti, F; Pozzilli, C; Montanari, E; Pappalardo, A; Piazza, L; Levi, A; Onesti, E; Pesci, I

2007-07-01

To evaluate the effects of education level and employment status on health-related quality of life (HRQoL) in a large cohort of patients affected by relapsing-remitting multiple sclerosis (RRMS). Patients This study included 648 patients with RRMS attending 40 Italian MS centers. Inclusion criteria were an Expanded Disability Status Scale (EDSS) score between 1.0 and 5.5; stable disease on enrollment; and no previous treatment with interferons, glatiramer acetate, or immunosuppressive drugs. Quality of life (QoL) was evaluated by the Multiple Sclerosis Quality of Life-54 questionnaire (MSQoL-54). Employed patients scored significantly higher than other patient groups in the majority of MSQoL-54 domains. Similarly, patients with academic degrees and secondary education had higher scores than those with primary education (ie, eight years of education) in several domains of HRQoL. Patients who were employed with a high educational level achieved significantly better scores than unemployed patients with a lower educational level. In multivariate analysis, occupation and educational level were found to be significant and independent predictors of HRQoL. The results of our study suggest the importance of sustaining employment after a recent diagnosis of MS. In addition, education has a great influence on HRQoL; a higher education level may determine a stronger awareness of the disease, and a better ability to cope with the challenges of a chronic disease such as MS.

Therapeutic neuroprotective agents for amyotrophic lateral sclerosis

PubMed Central

Pandya, Rachna S.; Zhu, Haining; Li, Wei; Bowser, Robert; Friedlander, Robert M.

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal chronic neurodegenerative disease whose hallmark is proteinaceous, ubiquitinated, cytoplasmic inclusions in motor neurons and surrounding cells. Multiple mechanisms proposed as responsible for ALS pathogenesis include dysfunction of protein degradation, glutamate excitotoxicity, mitochondrial dysfunction, apoptosis, oxidative stress, and inflammation. It is therefore essential to gain a better understanding of the underlying disease etiology and search for neuroprotective agents that might delay disease onset, slow progression, prolong survival, and ultimately reduce the burden of disease. Because riluzole, the only Food and Drug Administration (FDA)-approved treatment, prolongs the ALS patient’s life by only 3 months, new therapeutic agents are urgently needed. In this review, we focus on studies of various small pharmacological compounds targeting the proposed pathogenic mechanisms of ALS and discuss their impact on disease progression. PMID:23864030

Enantioselectivity in the Metabolism of Cyclophosphamide in Patients With Multiple or Systemic Sclerosis.

PubMed

de Castro, Francine Attié; Simões, Belinda Pinto; Coelho, Eduardo Barbosa; Lanchote, Vera Lucia

2017-06-01

The aim of this study was to evaluate the enantioselective pharmacokinetics of cyclophosphamide and its metabolites 4-hydroxycyclophosphamide and carboxyethylphosphoramide mustard in patients with systemic or multiple sclerosis. Patients with systemic sclerosis (n = 10) or multiple sclerosis (n = 10), genotyped for the allelic variants of CYP2C9*2 and CYP2C9*3 and of the CYP2B6 G516T polymorphism, were treated with 50 mg cyclophosphamide/kg daily for 4 days. Serial blood samples were collected up to 24 hours after administration of the last cyclophosphamide dose. Cyclophosphamide, 4-hydroxycyclophosphamide, and carboxyethylphosphoramide enantiomers were analyzed in plasma samples using liquid chromatography-tandem mass spectrometry coupled to chiral column Chiralcel OD-R or Chiralpak AD-RH. Cytokines IL-2, IL-4, IL-6, IL-8, IL-10, IL- 12p70, IL-17, TNF-α, and INT-δ in the plasma samples collected before cyclophosphamide infusion were analyzed by Milliplex MAP human cytokine/chemokine. Pharmacokinetic parameters showed higher plasma concentrations of (S)-(-)-cyclophosphamide (AUC 215.0 vs 186.2 μg·h/mL for multiple sclerosis patients and 219.1 vs 179.2 μg·h/mL for systemic sclerosis patients) and (R)-4-hydroxycyclophosphamide (AUC 5.6 vs 3.7 μg·h/mL for multiple sclerosis patients and 6.3 vs 5.6 μg·h/mL for systemic sclerosis patients) when compared to their enantiomers in both groups of patients, whereas the pharmacokinetics of the carboxyethylphosphoramide metabolite was not enantioselective. Cytokines' plasma concentrations were similar between multiple and systemic sclerosis groups. The pharmacokinetics of cyclophosphamide is enantioselective in patients with systemic sclerosis and multiple sclerosis, with higher plasma concentrations of the (S)-(-)-cyclophosphamide enantiomer due to the preferential formation of the (R)-4-hydroxycyclophosphamide metabolite. © 2017, The American College of Clinical Pharmacology.

Percutaneous endoscopic cecostomy (introducer method) in chronic intestinal pseudo-obstruction: Report of two cases and literature review.

PubMed

Küllmer, Armin; Schmidt, Arthur; Caca, Karel

2016-03-01

We report on two patients with recurrent episodes of chronic intestinal pseudo-obstruction (CIPO). A 50-year-old woman with severe multiple sclerosis and an 84-year-old man with Parkinson's disease and dementia had multiple hospital admissions because of pain and distended abdomen. Radiographic and endoscopic findings showed massive dilation of the colon without any evidence of obstruction. Conservative management resolved symptoms only for a short period of time. As these patients were poor candidates for any surgical treatment we carried out percutaneous endoscopic colostomy by placing a 20-Fr tube in the cecum with the introducer method. The procedure led to durable symptom relief without complications. We present these two cases and give a review through the existing literature of the procedure in CIPO. © 2015 Japan Gastroenterological Endoscopy Society.

Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease

PubMed Central

Germi, Raphaëlle; Bernard, Corinne; Garcia-Montojo, Marta; Deluen, Cécile; Farinelli, Laurent; Faucard, Raphaël; Veas, Francisco; Stefas, Ilias; Fabriek, Babs O; Van-Horssen, Jack; Van-der-Valk, Paul; Gerdil, Claire; Mancuso, Roberta; Saresella, Marina; Clerici, Mario; Marcel, Sébastien; Creange, Alain; Cavaretta, Rosella; Caputo, Domenico; Arru, Giannina; Morand, Patrice; Lang, Alois B; Sotgiu, Stefano; Ruprecht, Klemens; Rieckmann, Peter; Villoslada, Pablo; Chofflon, Michel; Boucraut, Jose; Pelletier, Jean; Hartung, Hans-Peter

2012-01-01

Background: The envelope protein from multiple sclerosis (MS) associated retroviral element (MSRV), a member of the Human Endogenous Retroviral family ‘W’ (HERV-W), induces dysimmunity and inflammation. Objective: The objective of this study was to confirm and specify the association between HERV-W/MSRV envelope (Env) expression and MS. Methods: 103 MS, 199 healthy controls (HC) and controls with other neurological diseases (28), chronic infections (30) or autoimmunity (30) were analysed with an immunoassay detecting Env in serum. Env RNA or DNA copy numbers in peripheral blood mononuclear cells (PBMC) were determined by a quantitative polymerase chain reaction (PCR). Env was detected by immunohistology in the brains of patients with MS with three specific monoclonals. Results: Env antigen was detected in a serum of 73% of patients with MS with similar prevalence in all clinical forms, and not in chronic infection, systemic lupus, most other neurological diseases and healthy donors (p<0.01). Cases with chronic inflammatory demyelinating polyneuropathy (5/8) and rare HC (4/103) were positive. RNA expression in PBMC and DNA copy numbers were significantly elevated in patients with MS versus HC (p<0.001). In patients with MS, DNA copy numbers were significantly increased in chronic progressive MS (secondary progressive MS vs relapsing–remitting MS (RRMS) p<0.001; primary progressive MS vs RRMS –<0.02). Env protein was evidenced in macrophages within MS brain lesions with particular concentrations around vascular elements. Conclusion: The association between MS disease and the MSRV-type HERV-W element now appears quite strong, as evidenced ex-vivo from serum and PBMC with post-mortem confirmation in brain lesions. Chronic progressive MS, RRMS and clinically isolated syndrome show different ELISA (Enzyme-Linked Immunosorbent Assay) and/or PCR profiles suggestive of an increase with disease evolution, and amplicon sequencing confirms the association with particular HERV-W elements. PMID:22457345

G-Protein-Coupled Receptor Gpr17 Expression in Two Multiple Sclerosis Remyelination Models.

PubMed

Nyamoya, Stella; Leopold, Patrizia; Becker, Birte; Beyer, Cordian; Hustadt, Fabian; Schmitz, Christoph; Michel, Anne; Kipp, Markus

2018-06-05

In multiple sclerosis patients, demyelination is prominent in both the white and gray matter. Chronic clinical deficits are known to result from acute or chronic injury to the myelin sheath and inadequate remyelination. The underlying molecular mechanisms of remyelination and its failure remain currently unclear. Recent studies have recognized G protein-coupled receptor 17 (GPR17) as an important regulator of oligodendrocyte development and remyelination. So far, the relevance of GPR17 for myelin repair was mainly tested in remyelinating white matter lesions. The relevance of GPR17 for gray matter remyelination as well as remyelination of chronic white matter lesions was not addressed so far. Here, we provide a detailed characterization of GPR17 expression during experimental de- and remyelination. Experimental lesions with robust and limited endogenous remyelination capacity were established by either acute or chronic cuprizone-induced demyelination. Furthermore, remyelinating lesions were induced by the focal injection of lysophosphatidylcholine (LPC) into the corpus callosum. GPR17 expression was analyzed by complementary techniques including immunohistochemistry, in situ hybridization, and real-time PCR. In control animals, GPR17 + cells were evenly distributed in the corpus callosum and cortex and displayed a highly ramified morphology. Virtually all GPR17 + cells also expressed the oligodendrocyte-specific transcription factor OLIG2. After acute cuprizone-induced demyelination, robust endogenous remyelination was evident in the white matter corpus callosum but not in the gray matter cortex. Endogenous callosal remyelination was paralleled by a robust induction of GPR17 expression which was absent in the gray matter cortex. Higher numbers of GPR17 + cells were as well observed after LPC-induced focal white matter demyelination. In contrast, densities of GPR17 + cells were comparable to control animals after chronic cuprizone-induced demyelination indicating quiescence of this cell population. Our findings demonstrate that GPR17 expression induction correlates with acute demyelination and sufficient endogenous remyelination. This strengthens the view that manipulation of this receptor might be a therapeutic opportunity to support endogenous remyelination.

Glucose uptake heterogeneity of the leg muscles is similar between patients with multiple sclerosis and healthy controls during walking.

PubMed

Kindred, John H; Ketelhut, Nathaniel B; Rudroff, Thorsten

2015-02-01

Difficulties in ambulation are one of the main problems reported by patients with multiple sclerosis. A previous study by our research group showed increased recruitment of muscle groups during walking, but the influence of skeletal muscle properties, such as muscle fiber activity, has not been fully elucidated. The purpose of this investigation was to use the novel method of calculating glucose uptake heterogeneity in the leg muscles of patients with multiple sclerosis and compare these results to healthy controls. Eight patients with multiple sclerosis (4 men) and 8 healthy controls (4 men) performed 15 min of treadmill walking at a comfortable self-selected speed following muscle strength tests. Participants were injected with ≈ 8 mCi of [(18)F]-fluorodeoxyglucose during walking after which positron emission tomography/computed tomography imaging was performed. No differences in muscle strength were detected between multiple sclerosis and control groups (P>0.27). Within the multiple sclerosis, group differences in muscle volume existed between the stronger and weaker legs in the vastus lateralis, semitendinosus, and semimembranosus (P<0.03). Glucose uptake heterogeneity between the groups was not different for any muscle group or individual muscle of the legs (P>0.16, P≥0.05). Patients with multiple sclerosis and healthy controls showed similar muscle fiber activity during walking. Interpretations of these results, with respect to our previous study, suggest that walking difficulties in patients with multiple sclerosis may be more associated with altered central nervous system motor patterns rather than alterations in skeletal muscle properties. Published by Elsevier Ltd.

The interpretation of physical activity, exercise, and sedentary behaviours by persons with multiple sclerosis.

PubMed

Kinnett-Hopkins, Dominique; Learmonth, Yvonne; Hubbard, Elizabeth; Pilutti, Lara; Roberts, Sarah; Fanning, Jason; Wójcicki, Thomas; McAuley, Edward; Motl, Robert

2017-11-07

This study adopted a qualitative research design with directed content analysis and examined the interpretations of physical activity, exercise, and sedentary behaviour by persons with multiple sclerosis. Fifty three persons with multiple sclerosis who were enrolled in an exercise trial took part in semi-structured interviews regarding personal interpretations of physical activity, exercise, and sedentary behaviours. Forty three percent of participants indicated a consistent understanding of physical activity, 42% of participants indicated a consistent understanding of exercise, and 83% of participants indicated a consistent understanding of sedentary behaviour with the standard definitions. There was evidence of definitional ambiguity (i.e., 57, 58, and 11% of the sample for physical activity, exercise, and sedentary behaviour, respectively); 6% of the sample inconsistently defined sedentary behaviour with standard definitions. Some participants described physical activity in a manner that more closely aligned with exercise and confused sedentary behaviour with exercise or sleeping/napping. Results highlight the need to provide and utilise consistent definitions for accurate understanding, proper evaluation and communication of physical activity, exercise, and sedentary behaviours among persons with multiple sclerosis. The application of consistent definitions may minimise ambiguity, alleviate the equivocality of findings in the literature, and translate into improved communication about these behaviours in multiple sclerosis. Implications for Rehabilitation The symptoms of multiple sclerosis can be managed through participation in physical activity and exercise. Persons with multiple sclerosis are not engaging in sufficient levels of physical activity and exercise for health benefits. Rehabilitation professionals should use established definitions of physical activity, exercise, and sedentary behaviours when communicating about these behaviours among persons with multiple sclerosis.

Aerobic exercise increases hippocampal volume and improves memory in multiple sclerosis: preliminary findings.

PubMed

Leavitt, V M; Cirnigliaro, C; Cohen, A; Farag, A; Brooks, M; Wecht, J M; Wylie, G R; Chiaravalloti, N D; DeLuca, J; Sumowski, J F

2014-01-01

Multiple sclerosis leads to prominent hippocampal atrophy, which is linked to memory deficits. Indeed, 50% of multiple sclerosis patients suffer memory impairment, with negative consequences for quality of life. There are currently no effective memory treatments for multiple sclerosis either pharmacological or behavioral. Aerobic exercise improves memory and promotes hippocampal neurogenesis in nonhuman animals. Here, we investigate the benefits of aerobic exercise in memory-impaired multiple sclerosis patients. Pilot data were collected from two ambulatory, memory-impaired multiple sclerosis participants randomized to non-aerobic (stretching) and aerobic (stationary cycling) conditions. The following baseline/follow-up measurements were taken: high-resolution MRI (neuroanatomical volumes), fMRI (functional connectivity), and memory assessment. Intervention was 30-minute sessions 3 times per week for 3 months. Aerobic exercise resulted in 16.5% increase in hippocampal volume and 53.7% increase in memory, as well as increased hippocampal resting-state functional connectivity. Improvements were specific, with no comparable changes in overall cerebral gray matter (+2.4%), non-hippocampal deep gray matter structures (thalamus, caudate: -4.0%), or in non-memory cognitive functioning (executive functions, processing speed, working memory: changes ranged from -11% to +4%). Non-aerobic exercise resulted in relatively no change in hippocampal volume (2.8%) or memory (0.0%), and no changes in hippocampal functional connectivity. This is the first evidence for aerobic exercise to increase hippocampal volume and connectivity and improve memory in multiple sclerosis. Aerobic exercise represents a cost-effective, widely available, natural, and self-administered treatment with no adverse side effects that may be the first effective memory treatment for multiple sclerosis patients.

Symptomatic therapy in multiple sclerosis

PubMed Central

Frohman, Teresa C.; Castro, Wanda; Shah, Anjali; Courtney, Ardith; Ortstadt, Jeffrey; Davis, Scott L.; Logan, Diana; Abraham, Thomas; Abraham, Jaspreet; Remington, Gina; Treadaway, Katherine; Graves, Donna; Hart, John; Stuve, Olaf; Lemack, Gary; Greenberg, Benjamin; Frohman, Elliot M.

2011-01-01

Multiple sclerosis is the most common disabling neurological disease of young adults. The ability to impact the quality of life of patients with multiple sclerosis should not only incorporate therapies that are disease modifying, but should also include a course of action for the global multidisciplinary management focused on quality of life and functional capabilities. PMID:21694806

Endogenous Task Shift Processes in Relapsing-Remitting Multiple Sclerosis

ERIC Educational Resources Information Center

Stablum, F.; Meligrana, L.; Sgaramella, T.; Bortolon, F.; Toso, V.

2004-01-01

This paper reports a study that was aimed to evaluate executive functions in relapsing-remitting multiple sclerosis patients. The groups tested comprised 22 relapsing-remitting multiple sclerosis patients, and 22 non-brain damaged controls. When one is engaged in two speeded tasks, not simultaneously but with some form of alternation, it is slower…

The Relevance of Depressive Symptoms and Social Support to Disability in Women with Multiple Sclerosis or Fibromyalgia

ERIC Educational Resources Information Center

Phillips, Lorraine J.

2010-01-01

Multiple sclerosis and fibromyalgia syndrome may spur substantial disability for those affected. Using structural equation modeling, this secondary analysis examined predictors of disability in women with multiple sclerosis (n = 118) and fibromyalgia syndrome (n = 197) recruited for separate wellness studies. Greater functional limitations, lower…

78 FR 40632 - Drawbridge Operation Regulation; Trent River, New Bern, NC

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-08

... navigation position for one hour on two consecutive days to accommodate the annual Bike Multiple Sclerosis... INFORMATION: The Event Director for the Bike Multiple Sclerosis: Historic New Bern Bike Ride, with approval... safe passage for cyclists during the Bike Multiple Sclerosis: Historic New Bern Bike Ride. The US 70...

Oxidative Stress is Increased in Serum from Mexican Patients with Relapsing-Remitting Multiple Sclerosis

PubMed Central

Ortiz, Genaro Gabriel; Macías-Islas, Miguel Ángel; Pacheco-Moisés, Fermín P.; Cruz-Ramos, José A.; Sustersik, Silvia; Barba, Elías Alejandro; Aguayo, Adriana

2009-01-01

Objective: To determine the oxidative stress markers in serum from patients with relapsing-remitting multiple sclerosis. Methods: Blood samples from healthy controls and 22 patients 15 women (7 aged from 20 to 30 and 8 were > 40 years old) and 7 men (5 aged from 20 to 30 and 2 were > 40 years old) fulfilling the McDonald Criteria and classified as having Relapsing-Remitting Multiple Sclerosis accordingly with Lublin were collected for oxidative stress markers quantification. Results: Nitric oxide metabolites (nitrates/nitrites), lipid peroxidation products (malondialdehyde plus 4-hidroxialkenals), and glutathione peroxidase activity were significantly increased in serum of subjects with relapsing-remitting multiple sclerosis in comparison with that of healthy controls. These data support the hypothesis that multiple sclerosis is a component closely linked to oxidative stress. PMID:19242067

Agent Orange exposure and prevalence of self-reported diseases in Korean Vietnam veterans.

PubMed

Yi, Sang-Wook; Ohrr, Heechoul; Hong, Jae-Seok; Yi, Jee-Jeon

2013-09-01

The aim of this study was to evaluate the association between Agent Orange exposure and self-reported diseases in Korean Vietnam veterans. A postal survey of 114 562 Vietnam veterans was conducted. The perceived exposure to Agent Orange was assessed by a 6-item questionnaire. Two proximity-based Agent Orange exposure indices were constructed using division/brigade-level and battalion/company-level unit information. Adjusted odds ratios (ORs) for age and other confounders were calculated using a logistic regression model. The prevalence of all self-reported diseases showed monotonically increasing trends as the levels of perceived self-reported exposure increased. The ORs for colon cancer (OR, 1.13), leukemia (OR, 1.56), hypertension (OR, 1.03), peripheral vasculopathy (OR, 1.07), enterocolitis (OR, 1.07), peripheral neuropathy (OR, 1.07), multiple nerve palsy (OR, 1.14), multiple sclerosis (OR, 1.24), skin diseases (OR, 1.05), psychotic diseases (OR, 1.07) and lipidemia (OR, 1.05) were significantly elevated for the high exposure group in the division/brigade-level proximity-based exposure analysis, compared to the low exposure group. The ORs for cerebral infarction (OR, 1.08), chronic bronchitis (OR, 1.05), multiple nerve palsy (OR, 1.07), multiple sclerosis (OR, 1.16), skin diseases (OR, 1.05), and lipidemia (OR, 1.05) were significantly elevated for the high exposure group in the battalion/company-level analysis. Korean Vietnam veterans with high exposure to Agent Orange experienced a higher prevalence of several self-reported chronic diseases compared to those with low exposure by proximity-based exposure assessment. The strong positive associations between perceived self-reported exposure and all self-reported diseases should be evaluated with discretion because the likelihood of reporting diseases was directly related to the perceived intensity of Agent Orange exposure.

High- and low-risk profiles for the development of multiple sclerosis within 10 years after optic neuritis: experience of the optic neuritis treatment trial.

PubMed

Beck, Roy W; Trobe, Jonathan D; Moke, Pamela S; Gal, Robin L; Xing, Dongyuan; Bhatti, M Tariq; Brodsky, Michael C; Buckley, Edward G; Chrousos, Georgia A; Corbett, James; Eggenberger, Eric; Goodwin, James A; Katz, Barrett; Kaufman, David I; Keltner, John L; Kupersmith, Mark J; Miller, Neil R; Nazarian, Sarkis; Orengo-Nania, Silvia; Savino, Peter J; Shults, William T; Smith, Craig H; Wall, Michael

2003-07-01

To identify factors associated with a high and low risk of developing multiple sclerosis after an initial episode of optic neuritis. Three hundred eighty-eight patients who experienced acute optic neuritis between July 1, 1988, and June 30, 1991, were followed up prospectively for the development of multiple sclerosis. Consenting patients were reassessed after 10 to 13 years. The 10-year risk of multiple sclerosis was 38% (95% confidence interval, 33%-43%). Patients (160) who had 1 or more typical lesions on the baseline magnetic resonance imaging (MRI) scan of the brain had a 56% risk; those with no lesions (191) had a 22% risk (P<.001, log rank test). Among the patients who had no lesions on MRI, male gender and optic disc swelling were associated with a lower risk of multiple sclerosis, as was the presence of the following atypical features for optic neuritis: no light perception vision; absence of pain; and ophthalmoscopic findings of severe optic disc edema, peripapillary hemorrhages, or retinal exudates. The 10-year risk of multiple sclerosis following an initial episode of acute optic neuritis is significantly higher if there is a single brain MRI lesion; higher numbers of lesions do not appreciably increase that risk. However, even when brain lesions are seen on MRI, more than 40% of the patients will not develop clinical multiple sclerosis after 10 years. In the absence of MRI lesions, certain demographic and clinical features seem to predict a very low likelihood of developing multiple sclerosis. This natural history information is a critical input for estimating a patient's 10-year multiple sclerosis risk and for weighing the benefit of initiating prophylactic treatment at the time of optic neuritis or other initial demyelinating events in the central nervous system.

Use of the Godin leisure-time exercise questionnaire in multiple sclerosis research: a comprehensive narrative review.

PubMed

Sikes, Elizabeth Morghen; Richardson, Emma V; Cederberg, Katie J; Sasaki, Jeffer E; Sandroff, Brian M; Motl, Robert W

2018-01-17

The Godin Leisure-Time Exercise Questionnaire has been a commonly applied measure of physical activity in research among persons with multiple sclerosis over the past decade. This paper provides a comprehensive description of its application and inclusion in research on physical activity in multiple sclerosis. This comprehensive, narrative review included papers that were published between 1985 and 2017, written in English, involved participants with multiple sclerosis as a primary population, measured physical activity, and cited one of the two original Godin papers. There is a broad scope of research that has included the Godin Leisure-Time Exercise Questionnaire in persons with multiple sclerosis. Overall, 8 papers evaluated its psychometric properties, 21 evaluated patterns of physical activity, 24 evaluated correlates or determinants of physical activity, 28 evaluated outcomes or consequences of physical activity, and 15 evaluated physical activity interventions. The Godin Leisure-Time Exercise Questionnaire is a valid self-report measure of physical activity in persons with multiple sclerosis, and further is an appropriate, simple, and effective tool for describing patterns of physical activity, examining correlates and outcomes of physical activity, and provides a sensitive outcome for measuring change in physical activity after an intervention. Implications for rehabilitation There is increasing interest in physical activity and its benefits in multiple sclerosis. The study of physical activity requires appropriate and standardized measures. The Godin Leisure-Time Exercise Questionnaire is a common self-report measure of physical activity for persons with multiple sclerosis. Godin Leisure-Time Exercise Questionnaire scores are reliable measures of physical activity in persons with multiple sclerosis. The Godin Leisure-Time Exercise Questionnaire further is an appropriate, simple, and effective tool for describing patterns of physical activity, examining correlates and outcomes of physical activity participation, and is an advantageous primary outcome for measuring change in physical activity in response to an intervention.

Fingolimod inhibits brain atrophy and promotes brain-derived neurotrophic factor in an animal model of multiple sclerosis.

PubMed

Smith, Paul A; Schmid, Cindy; Zurbruegg, Stefan; Jivkov, Magali; Doelemeyer, Arno; Theil, Diethilde; Dubost, Valérie; Beckmann, Nicolau

2018-05-15

Longitudinal brain atrophy quantification is a critical efficacy measurement in multiple sclerosis (MS) clinical trials and the determination of No Evidence of Disease Activity (NEDA). Utilising fingolimod as a clinically validated therapy we evaluated the use of repeated brain tissue volume measures during chronic experimental autoimmune encephalomyelitis (EAE) as a new preclinical efficacy measure. Brain volume changes were quantified using magnetic resonance imaging (MRI) at 7 Tesla and correlated to treatment-induced brain derived neurotrophic factor (BDNF) measured in blood, cerebrospinal fluid, spinal cord and brain. Serial brain MRI measurements revealed slow progressive brain volume loss in vehicle treated EAE mice despite a stable clinical score. Fingolimod (1 mg/kg) significantly ameliorated brain tissue atrophy in the cerebellum and striatum when administered from established EAE disease onwards. Fingolimod-dependent tissue preservation was associated with induction of BDNF specifically within the brain and co-localized with neuronal soma. In contrast, therapeutic teriflunomide (3 mg/kg) treatment failed to inhibit CNS autoimmune mediated brain degeneration. Finally, weekly anti-IL-17A antibody (15 mg/kg) treatment was highly efficacious and preserved whole brain, cerebellum and striatum volume. Fingolimod-mediated BDNF increases within the CNS may contribute to limiting progressive tissue loss during chronic neuroinflammation. Copyright © 2018 Elsevier B.V. All rights reserved.

Leisure time activities of Iranian patients with multiple sclerosis: a qualitative study

PubMed Central

Hosseini, Seyed Mohammad Sadegh; Asgari, Ali; Rassafiani, Mehdi; Yazdani, Farzaneh; Mazdeh, Mehrdokht

2016-01-01

Background: Leisure time is one of the most important aspects of life, especially for people with chronic diseases. The concept and types of leisure have frequently been evaluated in different socio-cultural populations. The aim of this study was to identify the nature of leisure activities among a sample of Iranian patients with multiple sclerosis (MS) and classify the identified types of activities in the context of Iranian culture. Methods: In this qualitative study, semi-structured interview was applied to gather data from 34 MS patients that were selected through purposive sampling. The interviews were continued up to the point of saturation. Content analysis was used to explore experiences of the interviewees regarding their leisure activities. Results: Six categories of leisure activities were extracted for the studied patients with MS i.e.physical, social, individual, art/cultural, educational and spiritual/religious. Conclusion: The results represented the range and heterogeneity of leisure activities amongst the MS patients. Considering participation in spiritual/religious and social activities as leisure time undertaking might reflect cultural diversity in the perception and use of time for recreation. For mental health promotion purposes, paying special attention to the types of activities that people of different socio-cultural background choose for their refreshment could help health care providers in giving tailored advice for patients with MS and other chronic debilitating disease. PMID:27123437

The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis.

PubMed

Morris, Gerwyn; Stubbs, Brendon; Köhler, Cristiano A; Walder, Ken; Slyepchenko, Anastasiya; Berk, Michael; Carvalho, André F

2018-04-04

Sleep and circadian abnormalities are prevalent and burdensome manifestations of diverse neuro-immune diseases, and may aggravate the course of several neuropsychiatric disorders. The underlying pathophysiology of sleep abnormalities across neuropsychiatric disorders remains unclear, and may involve the inter-play of several clinical variables and mechanistic pathways. In this review, we propose a heuristic framework in which reciprocal interactions of immune, oxidative and nitrosative stress, and mitochondrial pathways may drive sleep abnormalities across potentially neuroprogressive disorders. Specifically, it is proposed that systemic inflammation may activate microglial cells and astrocytes in brain regions involved in sleep and circadian regulation. Activated glial cells may secrete pro-inflammatory cytokines (for example, interleukin-1 beta and tumour necrosis factor alpha), nitric oxide and gliotransmitters, which may influence the expression of key circadian regulators (e.g., the Circadian Locomotor Output Cycles Kaput (CLOCK) gene). Furthermore, sleep disruption may further aggravate oxidative and nitrosative, peripheral immune activation, and (neuro) inflammation across these disorders in a vicious pathophysiological loop. This review will focus on chronic fatigue syndrome, bipolar disorder, and multiple sclerosis as exemplars of neuro-immune disorders. We conclude that novel therapeutic targets exploring immune and oxidative & nitrosative pathways (p.e. melatonin and molecular hydrogen) hold promise in alleviating sleep and circadian dysfunction in these disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Role of Fungi in the Etiology of Multiple Sclerosis

PubMed Central

Benito-León, Julián; Laurence, Martin

2017-01-01

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system. Infectious triggers of MS are being actively investigated. Substantial evidence supports the involvement of the Epstein-Barr virus (EBV), though other viruses, bacteria, protists, and fungi are also being considered. Many links between fungi and diseases involving chronic inflammation have been found recently. Evidence linking MS and fungi is reviewed here. The HLA-DRB1*15 allele group is the most important genetic risk factor of MS, and is a risk factor in several other conditions linked to fungal infections. Many biomarkers of MS are consistent with fungal infections, such as IL-17, chitotriosidase, and antibodies against fungi. Dimethyl fumarate (DMF), first used as an industrial fungicide, was recently repurposed to reduce MS symptoms. Its mechanisms of action in MS have not been firmly established. The low risk of MS during childhood and its moderate association with herpes simplex virus type 2 suggest genital exposure to microbes (including fungi) should be investigated as a possible trigger. Molecular and epidemiological evidence support a role for infections such as EBV in MS. Though fungal infections have not been widely studied in MS, many lines of evidence are consistent with a fungal etiology. Future microbiome and serological studies should consider fungi as a possible risk factor for MS, and future clinical studies should consider the effect of fungicides other than DMF on MS symptoms. PMID:29085329

Comparison of qualitative and quantitative analysis of T2-weighted MRI scans in chronic-progressive multiple sclerosis

NASA Astrophysics Data System (ADS)

Adams, Hans-Peter; Wagner, Simone; Koziol, James A.

1998-06-01

Magnetic resonance imaging (MRI) is routinely used for the diagnosis of multiple sclerosis (MS), and for objective assessment of the extent of disease as a marker of treatment efficacy in MS clinical trials. The purpose of this study is to compare the evaluation of T2-weighted MRI scans in MS patients using a semi-automated quantitative technique with an independent assessment by a neurologist. Baseline, 6- month, and 12-month T2-weighted MRI scans from 41 chronic progressive MS patients were examined. The lesion volume ranged from 0.50 to 51.56 cm2 (mean: 8.08 cm2). Reproducibility of the quantitative technique was assessed by the re-evaluation of a random subset of 20 scans, the coefficient of variation of the replicate determinations was 8.2%. The reproducibility of the neurologist evaluations was assessed by the re-evaluation of a random subset of 10 patients. The rank correlation between the results of the two methods was 0.097, which did not significantly differ from zero. Disease-related activity in T2-weighted MRI scans is a multi-dimensional construct, and is not adequately summarized solely by determination of lesion volume. In this setting, image analysis software should not only support storage and retrieval as sets of pixels, but should also support links to an anatomical dictionary.

Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach.

PubMed

Stampanoni Bassi, Mario; Gilio, Luana; Buttari, Fabio; Maffei, Pierpaolo; Marfia, Girolama A; Restivo, Domenico A; Centonze, Diego; Iezzi, Ennio

2017-01-01

Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS), structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the "clinico-radiological paradox." The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP) may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS) techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

Chronic cerebrospinal venous insufficiency in multiple sclerosis: clinical correlates from a multicentre study

PubMed Central

2011-01-01

Background Chronic cerebrospinal venous insufficiency (CCSVI) has recently been reported to be associated with multiple sclerosis (MS). However, its actual prevalence, possible association with specific MS phenotypes, and potential pathophysiological role are debated. Method We analysed the clinical data of 710 MS patients attending six centres (five Italian and one Canadian). All were submitted to venous Doppler sonography and diagnosed as having or not having CCSVI according to the criteria of Zamboni et al. Results Overall, CCSVI was diagnosed in 86% of the patients, but the frequency varied greatly between the centres. Even greater differences were found when considering singly the five diagnostic criteria proposed by Zamboni et al. Despite these differences, significant associations with clinical data were found, the most striking being age at disease onset (about five years greater in CCSVI-positive patients) and clinical severity (mean EDSS score about one point higher in CCSVI-positive patients). Patients with progressive MS were more likely to have CCSVI than those with relapsing-remitting MS. Conclusion The methods for diagnosing CCSVI need to be refined, as the between-centre differences, particularly in single criteria, were excessively high. Despite these discrepancies, the strong associations between CCSVI and MS phenotype suggest that the presence of CCSVI may favour a later development of MS in patients with a lower susceptibility to autoimmune diseases and may increase its severity. PMID:22029656

Adverse Structural and Functional Effects of Marijuana on the Brain: Evidence Reviewed.

PubMed

Mandelbaum, David E; de la Monte, Suzanne M

2017-01-01

The growing use and legalization of cannabis are leading to increased exposures across all age groups, including in adolescence. The touting of its medicinal values stems from anecdotal reports related to treatment of a broad range of illnesses including epilepsy, multiple sclerosis, muscle spasms, arthritis, obesity, cancer, Alzheimer disease, Parkinson disease, post-traumatic stress, inflammatory bowel disease, and anxiety. However, anecdotal data and the high level of interest in this treatment must not obscure objective assessments of any potential and realized short- and long-term adverse effects of cannabis, particularly with respect to age of onset and chronicity of exposure. This critical review focuses on evidence-based research designed to assess both therapeutic benefits and harmful effects of cannabis exposure and is combined with an illustration of the neuropathologic findings in a fatal case of cannabis-induced psychosis. The literature and reported case provide strong evidence that chronic cannabis abuse causes cognitive impairment and damages the brain, particularly white matter, where cannabinoid 1 receptors abound. Contrary to popular perception, there are few objective data supporting preferential use of cannabis over conventional therapy for restoration of central nervous system structure and function in disease states such as multiple sclerosis, epilepsy, or schizophrenia. Additional research is needed to determine if subsets of individuals with various neurological and psychiatric diseases derive therapeutic benefits from cannabis. Copyright © 2016. Published by Elsevier Inc.

Multimodal coherent anti-Stokes Raman scattering microscopy reveals microglia-associated myelin and axonal dysfunction in multiple sclerosis-like lesions in mice

PubMed Central

Imitola, Jaime; Côté, Daniel; Rasmussen, Stine; Xie, X. Sunney; Liu, Yingru; Chitnis, Tanuja; Sidman, Richard L.; Lin, Charles. P.; Khoury, Samia J.

2011-01-01

Myelin loss and axonal degeneration predominate in many neurological disorders; however, methods to visualize them simultaneously in live tissue are unavailable. We describe a new imaging strategy combining video rate reflectance and fluorescence confocal imaging with coherent anti-Stokes Raman scattering (CARS) microscopy tuned to CH2 vibration of myelin lipids, applied in live tissue of animals with chronic experimental autoimmune encephalomyelitis (EAE). Our method allows monitoring over time of demyelination and neurodegeneration in brain slices with high spatial resolution and signal-to-noise ratio. Local areas of severe loss of lipid signal indicative of demyelination and loss of the reflectance signal from axons were seen in the corpus callosum and spinal cord of EAE animals. Even in myelinated areas of EAE mice, the intensity of myelin lipid signals is significantly reduced. Using heterozygous knock-in mice in which green fluorescent protein replaces the CX3CR1 coding sequence that labels central nervous system microglia, we find areas of activated microglia colocalized with areas of altered reflectance and CARS signals reflecting axonal injury and demyelination. Our data demonstrate the use of multimodal CARS microscopy for characterization of demyelinating and neurodegenerative pathology in a mouse model of multiple sclerosis, and further confirm the critical role of microglia in chronic inflammatory neurodegeneration. PMID:21361672

Clinical benefits to vestibular rehabilitation in multiple sclerosis. Report of 4 cases.

PubMed

Zeigelboim, Bianca; Liberalesso, Paulo; Jurkiewicz, Ari; Klagenberg, Karlin

2010-01-01

Balance difficulties are common among multiple sclerosis patients. To evaluate the effectiveness of the Cawthorne and Cooksey protocol of vestibular rehabilitation (VR) exercises in reducing the physical, functional and emotional impact of multiple sclerosis among individuals who complained of vertigo. Four patients with remittent-recurrent multiple sclerosis underwent an interview, otorhinolaryngological and vestibular evaluation, VR exercises and the Dizziness Handicap Inventory pre- and post-intervention. There was significant improvement in the physical, functional and emotional aspects of the DHI after the completion of the VR. The VR exercises appeared useful in reducing subjective complaints of the study participants.

Distinct brain imaging characteristics of autoantibody-mediated CNS conditions and multiple sclerosis.

PubMed

Jurynczyk, Maciej; Geraldes, Ruth; Probert, Fay; Woodhall, Mark R; Waters, Patrick; Tackley, George; DeLuca, Gabriele; Chandratre, Saleel; Leite, Maria I; Vincent, Angela; Palace, Jacqueline

2017-03-01

Brain imaging characteristics of MOG antibody disease are largely unknown and it is unclear whether they differ from those of multiple sclerosis and AQP4 antibody disease. The aim of this study was to identify brain imaging discriminators between those three inflammatory central nervous system diseases in adults and children to support diagnostic decisions, drive antibody testing and generate disease mechanism hypotheses. Clinical brain scans of 83 patients with brain lesions (67 in the training and 16 in the validation cohort, 65 adults and 18 children) with MOG antibody (n = 26), AQP4 antibody disease (n = 26) and multiple sclerosis (n = 31) recruited from Oxford neuromyelitis optica and multiple sclerosis clinical services were retrospectively and anonymously scored on a set of 29 predefined magnetic resonance imaging features by two independent raters. Principal component analysis was used to perform an overview of patients without a priori knowledge of the diagnosis. Orthogonal partial least squares discriminant analysis was used to build models separating diagnostic groups and identify best classifiers, which were then tested on an independent cohort set. Adults and children with MOG antibody disease frequently had fluffy brainstem lesions, often located in pons and/or adjacent to fourth ventricle. Children across all conditions showed more frequent bilateral, large, brainstem and deep grey matter lesions. MOG antibody disease spontaneously separated from multiple sclerosis but overlapped with AQP4 antibody disease. Multiple sclerosis was discriminated from MOG antibody disease and from AQP4 antibody disease with high predictive values, while MOG antibody disease could not be accurately discriminated from AQP4 antibody disease. Best classifiers between MOG antibody disease and multiple sclerosis were similar in adults and children, and included ovoid lesions adjacent to the body of lateral ventricles, Dawson's fingers, T1 hypointense lesions (multiple sclerosis), fluffy lesions and three lesions or less (MOG antibody). In the validation cohort patients with antibody-mediated conditions were differentiated from multiple sclerosis with high accuracy. Both antibody-mediated conditions can be clearly separated from multiple sclerosis on conventional brain imaging, both in adults and children. The overlap between MOG antibody oligodendrocytopathy and AQP4 antibody astrocytopathy suggests that the primary immune target is not the main substrate for brain lesion characteristics. This is also supported by the clear distinction between multiple sclerosis and MOG antibody disease both considered primary demyelinating conditions. We identify discriminatory features, which may be useful in classifying atypical multiple sclerosis, seronegative neuromyelitis optica spectrum disorders and relapsing acute disseminated encephalomyelitis, and characterizing cohorts for antibody discovery. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Microcystic macular oedema in multiple sclerosis is associated with disease severity

PubMed Central

Gelfand, Jeffrey M.; Nolan, Rachel; Schwartz, Daniel M.; Graves, Jennifer

2012-01-01

Macular oedema typically results from blood–retinal barrier disruption. It has recently been reported that patients with multiple sclerosis treated with FTY-720 (fingolimod) may exhibit macular oedema. Multiple sclerosis is not otherwise thought to be associated with macular oedema except in the context of comorbid clinical uveitis. Despite a lack of myelin, the retina is a site of inflammation and microglial activation in multiple sclerosis and demonstrates significant neuronal and axonal loss. We unexpectedly observed microcystic macular oedema using spectral domain optical coherence tomography in patients with multiple sclerosis who did not have another reason for macular oedema. We therefore evaluated spectral domain optical coherence tomography images in consecutive patients with multiple sclerosis for microcystic macular oedema and examined correlations between macular oedema and visual and ambulatory disability in a cross-sectional analysis. Participants were excluded if there was a comorbidity that could account for the presence of macular oedema, such as uveitis, diabetes or other retinal disease. A microcystic pattern of macular oedema was observed on optical coherence tomography in 15 of 318 (4.7%) patients with multiple sclerosis. No macular oedema was identified in 52 healthy controls assessed over the same period. The microcystic oedema predominantly involved the inner nuclear layer of the retina and tended to occur in small, discrete patches. Patients with multiple sclerosis with microcystic macular oedema had significantly worse disability [median Expanded Disability Score Scale 4 (interquartile range 3–6)] than patients without macular oedema [median Expanded Disability Score Scale 2 (interquartile range 1.5–3.5)], P = 0.0002. Patients with multiple sclerosis with microcystic macular oedema also had higher Multiple Sclerosis Severity Scores, a measure of disease progression, than those without oedema [median of 6.47 (interquartile range 4.96–7.98) versus 3.65 (interquartile range 1.92–5.87), P = 0.0009]. Microcystic macular oedema occurred more commonly in eyes with prior optic neuritis than eyes without prior optic neuritis (50 versus 27%) and was associated with lower visual acuity (median logMAR acuity of 0.17 versus −0.1) and a thinner retinal nerve fibre layer. The presence of microcystic macular oedema in multiple sclerosis suggests that there may be breakdown of the blood–retinal barrier and tight junction integrity in a part of the nervous system that lacks myelin. Microcystic macular oedema may also contribute to visual dysfunction beyond that explained by nerve fibre layer loss. Microcystic changes need to be assessed, and potentially adjusted for, in clinical trials that evaluate macular volume as a marker of retinal ganglion cell survival. These findings also have implications for clinical monitoring in patients with multiple sclerosis on sphingosine 1-phosphate receptor modulating agents. PMID:22539259

Deficits in Social Cognition: An Unveiled Signature of Multiple Sclerosis.

PubMed

Chalah, Moussa A; Ayache, Samar S

2017-03-01

Multiple sclerosis (MS) is a chronic progressive inflammatory disease of the central nervous system, representing the primary cause of non-traumatic disability in young adults. Cognitive dysfunction can affect patients at any time during the disease process and might alter the six core functional domains. Social cognition is a multi-component construct that includes the theory of mind, empathy and social perception of emotions from facial, bodily and vocal cues. Deficits in this cognitive faculty might have a drastic impact on interpersonal relationships and quality of life (QoL). Although exhaustive data exist for non-social cognitive functions in MS, only a little attention has been paid for social cognition. The objectives of the present work are to reappraise the definition and anatomy of social cognition and evaluate the integrity of this domain across MS studies. We will put special emphasis on neuropsychological and neuroimaging studies concerning social cognitive performance in MS. Studies were selected in conformity with PRISMA guidelines. We looked for computerized databases (PubMed, Medline, and Scopus) that index peer-reviewed journals to identify published reports in English and French languages that mention social cognition and multiple sclerosis, regardless of publication year. We combined keywords as follows: (facial emotion or facial expression or emotional facial expressions or theory of mind or social cognition or empathy or affective prosody) AND multiple sclerosis AND (MRI or functional MRI or positron emission tomography or functional imaging or structural imaging). We also scanned references from articles aiming to get additional relevant studies. In total, 26 studies matched the abovementioned criteria (26 neuropsychological studies including five neuroimaging studies). Available data support the presence of social cognitive deficits even at early stages of MS. The increase in disease burden along with the "multiple disconnection syndrome" resulting from gray and white matters pathology might exceed the "threshold for cerebral tolerance" and can manifest as deficits in social cognition. Admitting the impact of the latter on patients' social functioning, a thorough screening for such deficits is crucial to improving patients' QoL. (JINS, 2017, 23, 266-286).

Fingolimod Prescribed for the Treatment of Multiple Sclerosis in Patients Younger Than Age 18 Years.

PubMed

Fragoso, Yara Dadalti; Alves-Leon, Soniza Vieira; Barreira, Amilton Antunes; Callegaro, Dagoberto; Brito Ferreira, Maria Lucia; Finkelsztejn, Alessandro; Gomes, Sidney; Magno Goncalves, Marcus Vinicius; Moraes Machado, Maria Iris; Marques, Vanessa Daccach; Cunha Matta, Andre Palma; Papais-Alvarenga, Regina Maria; Apostolos Pereira, Samira Luisa; Tauil, Carlos Bernardo

2015-08-01

There have been no clinical trials for approval of medications for treating multiple sclerosis in patients younger than age 18 years. All treatments are based on personal experience and data from open observational studies. Fingolimod is an oral drug for multiple sclerosis that has been shown to be efficient and safe in adults. The aim of our study is to describe patients with multiple sclerosis who started treatment with fingolimod before the age of 18 years. Seventeen patients treated with fingolimod were identified in the Brazilian database of children and adolescents with multiple sclerosis. The average time of use of the drug was 8.6 months. Fingolimod showed a good safety and efficacy profile in these patients, all of whom had very active multiple sclerosis. After starting treatment with fingolimod, only one patient had a relapse and a new lesion on magnetic resonance imaging. The patients' degree of disability did not progress. No major adverse events were reported in relation to the first dose of the drug, nor in the short- and medium-term treatment. No patient has been followed for longer than 18 months, thus limiting long-term conclusions. Off-label use of fingolimod in patients younger than age 18 years may be a good therapeutic option for multiple sclerosis control. Copyright © 2015 Elsevier Inc. All rights reserved.

Therapeutics for multiple sclerosis symptoms.

PubMed

Ben-Zacharia, Aliza Bitton

2011-01-01

Symptoms management in multiple sclerosis is an integral part of its care. Accurate assessment and addressing the different symptoms provides increased quality of life among patients with multiple sclerosis. Multiple sclerosis symptoms may be identified as primary, secondary, or tertiary symptoms. Primary symptoms, such as weakness, sensory loss, and ataxia, are directly related to demyelination and axonal loss. Secondary symptoms, such as urinary tract infections as a result of urinary retention, are a result of the primary symptoms. Tertiary symptoms, such as reactive depression or social isolation, are a result of the social and psychological consequences of the disease. Common multiple sclerosis symptoms include fatigue and weakness; decreased balance, spasticity and gait problems; depression and cognitive issues; bladder, bowel, and sexual deficits; visual and sensory loss; and neuropathic pain. Less-common symptoms include dysarthria and dysphagia, vertigo, and tremors. Rare symptoms in multiple sclerosis include seizures, hearing loss, and paralysis. Symptom management includes nonpharmacological methods, such as rehabilitation and psychosocial support, and pharmacological methods, ie, medications and surgical procedures. The keys to symptom management are awareness, knowledge, and coordination of care. Symptoms have to be recognized and management needs to be individualized. Multiple sclerosis therapeutics include nonpharmacological strategies that consist of lifestyle modifications, rehabilitation, social support, counseling, and pharmacological agents or surgical procedures. The goal is vigilant management to improve quality of life and promote realistic expectations and hope. © 2011 Mount Sinai School of Medicine.

Internal jugular vein blood flow in multiple sclerosis patients and matched controls.

PubMed

Mancini, Marcello; Lanzillo, Roberta; Liuzzi, Raffaele; Di Donato, Orlando; Ragucci, Monica; Monti, Serena; Salvatore, Elena; Morra, Vincenzo Brescia; Salvatore, Marco

2014-01-01

The aim of the study was to investigate the Internal Jugular Veins dynamics using contrast enhanced ultrasonography in Multiple Sclerosis patients, clinically isolated syndrome patients and healthy controls. Contrast enhanced ultrasonography imaging of the Internal Jugular Vein was performed in fifty-eight patients with Multiple Sclerosis, seven clinically isolated syndrome patients and in thirteen healthy controls. Time-intensity curves were quantified using a semi-automated method and compared with clinical disease outcomes. Wash-out parameters were calculated and six Time-intensity curves shapes were created. Significantly reduction of wash-out rate in Internal Jugular Veins was detected in Multiple Sclerosis patients compared to healthy controls [22.2% (2.7%-65.9%) vs. 33.4% (16.2%-76.8%); P<0.005]. Internal Jugular Vein enhancement was heterogeneous in patients with Multiple Sclerosis and consisted of slow wash-out Time-intensity curves shapes, compared with almost only one type of Time-intensity curves shape in control subjects that correspond to fast enhancement and fast wash-out. The vein wash-in parameters were similar in Multiple Sclerosis group compared with controls. A significant correlation was found between Internal Jugular Vein wash-out and level of disability (R =  -0.402, p<0.05). Contrast enhanced ultrasonography of the Internal Jugular Vein with time intensity curve analysis revealed alterations of cerebral venous outflow in Multiple Sclerosis patients, however mechanisms that determine this condition remains unclear.

Diffusion tensor imaging of the optic tracts in multiple sclerosis: association with retinal thinning and visual disability.

PubMed

Dasenbrock, Hormuzdiyar H; Smith, Seth A; Ozturk, Arzu; Farrell, Sheena K; Calabresi, Peter A; Reich, Daniel S

2011-04-01

Visual disability is common in multiple sclerosis, but its relationship to abnormalities of the optic tracts remains unknown. Because they are only rarely affected by lesions, the optic tracts may represent a good model for assessing the imaging properties of normal-appearing white matter in multiple sclerosis. Whole-brain diffusion tensor imaging was performed on 34 individuals with multiple sclerosis and 26 healthy volunteers. The optic tracts were reconstructed by tractography, and tract-specific diffusion indices were quantified. In the multiple-sclerosis group, peripapillary retinal nerve-fiber-layer thickness and total macular volume were measured by optical coherence tomography, and visual acuity at 100%, 2.5%, and 1.25% contrast was examined. After adjusting for age and sex, optic-tract mean and perpendicular diffusivity were higher (P=.002) in multiple sclerosis. Lower optic-tract fractional anisotropy was correlated with retinal nerve-fiber-layer thinning (r=.51, P=.003) and total-macular-volume reduction (r=.59, P=.002). However, optic-tract diffusion indices were not specifically correlated with visual acuity or with their counterparts in the optic radiation. Optic-tract diffusion abnormalities are associated with retinal damage, suggesting that both may be related to optic-nerve injury, but do not appear to contribute strongly to visual disability in multiple sclerosis. Copyright © 2010 by the American Society of Neuroimaging.

Diffusion Tensor Imaging of the Optic Tracts in Multiple Sclerosis: Association with Retinal Thinning and Visual Disability

PubMed Central

Dasenbrock, Hormuzdiyar H.; Smith, Seth A.; Ozturk, Arzu; Farrell, Sheena K.; Calabresi, Peter A.; Reich, Daniel S.

2009-01-01

Background and purpose Visual disability is common in multiple sclerosis, but its relationship to abnormalities of the optic tracts remains unknown. Because they are only rarely affected by lesions, the optic tracts may represent a good model for assessing the imaging properties of normal-appearing white matter in multiple sclerosis. Methods Whole-brain diffusion tensor imaging was performed on 34 individuals with multiple sclerosis and 26 healthy volunteers. The optic tracts were reconstructed by tractography, and tract-specific diffusion indices were quantified. In the multiple-sclerosis group, peripapillary retinal nerve-fiber-layer thickness and total macular volume were measured by optical coherence tomography, and visual acuity at 100%, 2.5%, and 1.25% contrast was examined. Results After adjusting for age and sex, optic-tract mean and perpendicular diffusivity were higher (p=0.002) in multiple sclerosis. Lower optic-tract fractional anisotropy was correlated with retinal nerve-fiber-layer thinning (r=0.51, p=0.003) and total-macular-volume reduction (r=0.59, p=0.002). However, optic-tract diffusion indices were not specifically correlated with visual acuity or with their counterparts in the optic radiation. Conclusions Optic-tract diffusion abnormalities are associated with retinal damage, suggesting that both may be related to optic-nerve injury, but do not appear to contribute strongly to visual disability in multiple sclerosis. PMID:20331501

Symptomatic Therapy and Rehabilitation in Primary Progressive Multiple Sclerosis

PubMed Central

Khan, Fary; Amatya, Bhasker; Turner-Stokes, Lynne

2011-01-01

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system and a major cause of chronic neurological disability in young adults. Primary progressive MS (PPMS) constitutes about 10% of cases, and is characterized by a steady decline in function with no acute attacks. The rate of deterioration from disease onset is more rapid than relapsing remitting and secondary progressive MS types. Multiple system involvement at onset and rapid early progression have a worse prognosis. PPMS can cause significant disability and impact on quality of life. Recent studies are biased in favour of relapsing remitting patients as treatment is now available for them and they are more likely to be seen at MS clinics. Since prognosis for PPMS is worse than other types of MS, the focus of rehabilitation is on managing disability and enhancing participation, and application of a “neuropalliative” approach as the disease progresses. This chapter presents the symptomatic treatment and rehabilitation for persons with MS, including PPMS. A multidisciplinary approach optimizes the intermediate and long-term medical, psychological and social outcomes in this population. Restoration and maintenance of functional independence and societal reintegration, and issues relating to quality of life are addressed in rehabilitation processes. PMID:22013521

Clustering of multiple sclerosis in Galion, Ohio, 1982-1985

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ingalls, T.H.

1989-09-01

Epidemiologic evidence indicates that the outbreak of 30-40 cases of multiple sclerosis and other demyelinating syndromes in Galion, Ohio, USA, during 1982-1985 was related to an excess concentration of heavy-metal wastes, especially of cadmium and chromium in sewage and river water. Both multiple sclerosis and myasthenia gravis were diagnosed by board-certified neurologists.

Clinical commentary on "Paroxysmal kinesigenic dyskinesia-like phenotype in multiple sclerosis" and "Secondary paroxysmal dyskinesia in multiple sclerosis: Clinical-radiological features and treatment. Case report of seven patients".

PubMed

Pareés, Isabel

2017-11-01

This clinical commentary discusses the phenomenology and treatment of paroxysmal dyskinesia in patients with multiple sclerosis. It calls for a consensus on the definition as well as for larger studies to better understand this unusual clinical association.

Intranasal Insulin for Improving Cognitive Function in Multiple Sclerosis

DTIC Science & Technology

2017-10-01

Insulin, Symbol Digit Modalities Test , Minimal Assessment of Cognitive Function in Multiple Sclerosis 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...going to evaluate if intranasal insulin improves cognition in people with MS, as assessed by standardized cognitive assessment tests . 2. KEYWORDS...Multiple Sclerosis, Cognitive Impairment, Neurodegenerative diseases, Intranasal Insulin, Symbol Digit Modalities Test , Minimal Assessment of Cognitive

Reliability and Clinical Significance of Mobility and Balance Assessments in Multiple Sclerosis

ERIC Educational Resources Information Center

Learmonth, Yvonne C.; Paul, Lorna; McFadyen, Angus K.; Mattison, Paul; Miller, Linda

2012-01-01

The aim of the study was to establish the test-retest reliability, clinical significance and precision of four mobility and balance measures--the Timed 25-Foot Walk, Six-minute Walk, Timed Up and Go and the Berg Balance Scale--in individuals moderately affected by multiple sclerosis. Twenty four participants with multiple sclerosis (Extended…

76 FR 17530 - Special Local Regulations and Safety Zones; Recurring Events in Northern New England

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-30

...'' N 069[deg] 31'56'' W. 8.6 Multiple Sclerosis Regatta.... Event Type: Regatta and Sailboat Race. Sponsor: Maine Chapter, Multiple Sclerosis Society. Date: A one day event on Saturday during the third... 070[deg] 13'51'' W. 8.7 Multiple Sclerosis Harborfest Event Type: Power Boat Tugboat Race. Race...

75 FR 32280 - Safety Zones; Marine Events Within the Captain of the Port Sector Northern New England Area of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-08

.... Sponsor: Maine Chapter, Multiple Sclerosis Society. Date: August 21, 2010. Time: 11 am to 2 pm. Location... Sailboat Race. Sponsor: Maine Chapter, Multiple Sclerosis Society. Date: August 21, 2010. Time: 10 am to 4... Tugboat Muster. Event Type: Power Boat Race. Sponsor: Maine Chapter, National Multiple Sclerosis Society...

Is Hypovitaminosis D One of the Environmental Risk Factors for Multiple Sclerosis?

ERIC Educational Resources Information Center

Pierrot-Deseilligny, Charles; Souberbielle, Jean-Claude

2010-01-01

The role of hypovitaminosis D as a possible risk factor for multiple sclerosis is reviewed. First, it is emphasized that hypovitaminosis D could be only one of the risk factors for multiple sclerosis and that numerous other environmental and genetic risk factors appear to interact and combine to trigger the disease. Secondly, the classical…

Innate lymphoid cells in autoimmunity and chronic inflammatory diseases.

PubMed

Xiong, Tingting; Turner, Jan-Eric

2018-03-22

Abnormal activation of the innate immune system is a common feature of autoimmune and chronic inflammatory diseases. Since their identification as a separate family of leukocytes, innate lymphoid cells (ILCs) have emerged as important effector cells of the innate immune system. Alterations in ILC function and subtype distribution have been observed in a variety of immune-mediated diseases in humans and evidence from experimental models suggests a subtype specific role of ILCs in the pathophysiology of autoimmune inflammation. In this review, we discuss recent advances in the understanding of ILC biology in autoimmune and chronic inflammatory disorders, including multiple sclerosis, inflammatory bowel diseases, psoriasis, and rheumatic diseases, with a special focus on the potential of ILCs as therapeutic targets for the development of novel treatment strategies in humans.

Chronic inflammation in refractory hippocampal sclerosis-related temporal lobe epilepsy.

PubMed

Gales, Jordan M; Prayson, Richard A

2017-10-01

Emerging evidence suggests chronic inflammation may play a role in hippocampal sclerosis-associated temporal lobe epilepsy. We sought to systematically evaluate for its presence in a group of 315 patients who underwent surgery for medically-refractory epilepsy and who had hippocampal sclerosis. Upon histologic review of hematoxylin and eosin stained tissue sections, 95 (41%) cases demonstrated the presence of lymphocytes within the perivascular region and diffusely within the brain parenchyma. Those cases with chronic inflammation evident on hematoxylin and eosin staining were significantly more likely to experience a post-operative seizure recurrence than those without it (p=0.03). In 9 cases of hippocampi with chronic inflammation observed on hematoxylin and eosin stained sections, there was a mixture of both T (CD3+) and B (CD20+) lymphocytes located around blood vessels and interspersed within the brain parenchyma and a predominance of CD4 positive T cells versus CD8 positive cells. Ten hippocampi, apparently devoid of chronic inflammation upon inspection with hematoxylin and eosin stained sections, were stained with the lymphocyte common antigen CD45. In all 10 cases, scattered lymphoid cells were observed in the brain parenchyma, suggesting some level of chronic inflammation may be present in more cases than casual inspection might suggest. This study was the first to evaluate the incidence of chronic inflammation within a large temporal lobe epilepsy population. The study findings suggest chronic inflammation may be a more common component of hippocampal sclerosis -associated temporal lobe epilepsy than previously believed. Copyright © 2017 Elsevier Inc. All rights reserved.

[Assessment of exposure to tobacco smoke in a selected group of patients with multiple sclerosis from the Upper Silesia region].

PubMed

Dobosz, Cezary; Tyrpień, Krystyna; Pierzchała, Krystyna

2012-01-01

In recent years, the increase in the incidence of multiple sclerosis (MS - Multiple Sclerosis) is observed. and the direct cause of the symptoms of multiple sclerosis is myelin nerves damage. It can be concluded that the environmental factor is at least partly responsible for the occurrence of this disease. For the development of this disease are responsible, in addition to genetic factors, compounds present in many parts of the environment. Many of these compounds may adversely affect the redox equilibrium of the body, exacerbating radicalgenesis and decreasing antioxidant defenses. Multiple sclerosis is usually diagnosed in early adulthood, during most daily activities. Effects of SM on living standards includes not only the medical aspect, but also social, economic and emotional aspect. Polish population is a high risk zone regarding multiple sclerosis. The aim of this study was a preliminary assessment of selected environmental exposure factors in the pathogenesis of multiple sclerosis with regard to exposure to tobacco smoke with the author's survey of patients from the region of Upper Silesia. Most MS patients (32) in the study group (suffering from MS from 2 to 44 years) are inhabitants of agglomeration of over 50 thousand citizens, from the area of Gliwice, Bytom and Zabrze (43.75%). In investigated group 46.88% MS patients from Silesia region were exposed to tobacco smoke, of which 21.88% actively smoke. Patients with MS, in order not to worsen their disease manifestation, should stop smoking and increase, if possible, any physical activities. These data will be incorporated into a wide-ranging research to clarify the role of selected environmental factors in a very complex and still not fully explored the pathogenesis of multiple sclerosis in Upper Silesia.

Progressive multiple sclerosis: from pathogenic mechanisms to treatment.

PubMed

Correale, Jorge; Gaitán, María I; Ysrraelit, María C; Fiol, Marcela P

2017-03-01

During the past decades, better understanding of relapsing-remitting multiple sclerosis disease mechanisms have led to the development of several disease-modifying therapies, reducing relapse rates and severity, through immune system modulation or suppression. In contrast, current therapeutic options for progressive multiple sclerosis remain comparatively disappointing and challenging. One possible explanation is a lack of understanding of pathogenic mechanisms driving progressive multiple sclerosis. Furthermore, diagnosis is usually retrospective, based on history of gradual neurological worsening with or without occasional relapses, minor remissions or plateaus. In addition, imaging methods as well as biomarkers are not well established. Magnetic resonance imaging studies in progressive multiple sclerosis show decreased blood-brain barrier permeability, probably reflecting compartmentalization of inflammation behind a relatively intact blood-brain barrier. Interestingly, a spectrum of inflammatory cell types infiltrates the leptomeninges during subpial cortical demyelination. Indeed, recent magnetic resonance imaging studies show leptomeningeal contrast enhancement in subjects with progressive multiple sclerosis, possibly representing an in vivo marker of inflammation associated to subpial demyelination. Treatments for progressive disease depend on underlying mechanisms causing central nervous system damage. Immunity sheltered behind an intact blood-brain barrier, energy failure, and membrane channel dysfunction may be key processes in progressive disease. Interfering with these mechanisms may provide neuroprotection and prevent disability progression, while potentially restoring activity and conduction along damaged axons by repairing myelin. Although most previous clinical trials in progressive multiple sclerosis have yielded disappointing results, important lessons have been learnt, improving the design of novel ones. This review discusses mechanisms involved in progressive multiple sclerosis, correlations between histopathology and magnetic resonance imaging studies, along with possible new therapeutic approaches. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Childhood infections and risk of multiple sclerosis.

PubMed

Bager, Peter; Nielsen, Nete Munk; Bihrmann, Kristine; Frisch, Morten; Hjalgrim, Henrik; Wohlfart, Jan; Koch-Henriksen, Nils; Melbye, Mads; Westergaard, Tine

2004-11-01

Multiple sclerosis has been hypothesized to be the result from an aberrant immune response possibly triggered by delayed exposure to a common childhood infection. Because the vast majority of previous studies testing this hypothesis have been based on a history of childhood infections recalled years to decades later in adulthood, we investigated whether age at six common childhood infections was associated with risk of multiple sclerosis, using information recalled in the childhood of a historical cohort of school children in Denmark. Cases included all individuals with multiple sclerosis in the country born between 1940 and 1975, who had attended school in the capital, Copenhagen. Controls were age- and sex-matched peers. School health records were obtained for all subjects. The records contained information on measles, pertussis, scarlet fever, birth order, sibship size, social class of the father, school years, and name of school and attended school classes for children born since 1940 (n(cases) = 455, n(controls) = 1801). For children born since 1950, the records also contained information on rubella, varicella and mumps (n(cases) = 182, n(controls) = 690). Neither age at infection with measles, rubella, varicella, mumps, pertussis and scarlet fever (upper age limit, 14 years) nor the cumulative number of these infections between the ages of 10 and 14 years was associated with the risk of multiple sclerosis. In addition, the risk of multiple sclerosis was not associated with birth order or social class. No clustering of multiple sclerosis in school classes was observed. Our findings suggest that measles, rubella, mumps, varicella, pertussis and scarlet fever, even if acquired late in childhood, are not associated with increased risk of multiple sclerosis later in life.

Disconnection mechanism and regional cortical atrophy contribute to impaired processing of facial expressions and theory of mind in multiple sclerosis: a structural MRI study.

PubMed

Mike, Andrea; Strammer, Erzsebet; Aradi, Mihaly; Orsi, Gergely; Perlaki, Gabor; Hajnal, Andras; Sandor, Janos; Banati, Miklos; Illes, Eniko; Zaitsev, Alexander; Herold, Robert; Guttmann, Charles R G; Illes, Zsolt

2013-01-01

Successful socialization requires the ability of understanding of others' mental states. This ability called as mentalization (Theory of Mind) may become deficient and contribute to everyday life difficulties in multiple sclerosis. We aimed to explore the impact of brain pathology on mentalization performance in multiple sclerosis. Mentalization performance of 49 patients with multiple sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2-weighted three-dimensional brain MRI images were acquired at 3Tesla from patients with multiple sclerosis and 18 gender- and age matched healthy controls. We assessed overall brain cortical thickness in patients with multiple sclerosis and the scanned healthy controls, and measured the total and regional T1 and T2 white matter lesion volumes in patients with multiple sclerosis. Performances in tests of recognition of mental states and emotions from facial expressions and eye gazes correlated with both total T1-lesion load and regional T1-lesion load of association fiber tracts interconnecting cortical regions related to visual and emotion processing (genu and splenium of corpus callosum, right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, uncinate fasciculus). Both of these tests showed correlations with specific cortical areas involved in emotion recognition from facial expressions (right and left fusiform face area, frontal eye filed), processing of emotions (right entorhinal cortex) and socially relevant information (left temporal pole). Thus, both disconnection mechanism due to white matter lesions and cortical thinning of specific brain areas may result in cognitive deficit in multiple sclerosis affecting emotion and mental state processing from facial expressions and contributing to everyday and social life difficulties of these patients.

Impaired heel to toe progression during gait is related to reduced ankle range of motion in people with Multiple Sclerosis.

PubMed

Psarakis, Michael; Greene, David; Moresi, Mark; Baker, Michael; Stubbs, Peter; Brodie, Matthew; Lord, Stephen; Hoang, Phu

2017-11-01

Gait impairment in people with Multiple Sclerosis results from neurological impairment, muscle weakness and reduced range of motion. Restrictions in passive ankle range of motion can result in abnormal heel-to-toe progression (weight transfer) and inefficient gait patterns in people with Multiple Sclerosis. The purpose of this study was to determine the associations between gait impairment, heel-to-toe progression and ankle range of motion in people with Multiple Sclerosis. Twelve participants with Multiple Sclerosis and twelve healthy age-matched participants were assessed. Spatiotemporal parameters of gait and individual footprint data were used to investigate group differences. A pressure sensitive walkway was used to divide each footprint into three phases (contact, mid-stance, propulsive) and calculate the heel-to-toe progression during the stance phase of gait. Compared to healthy controls, people with Multiple Sclerosis spent relatively less time in contact phase (7.8% vs 25.1%) and more time in the mid stance phase of gait (57.3% vs 33.7%). Inter-limb differences were observed in people with Multiple Sclerosis between the affected and non-affected sides for contact (7.8% vs 15.3%) and mid stance (57.3% and 47.1%) phases. Differences in heel-to-toe progression remained significant after adjusting for walking speed and were correlated with walking distance and ankle range of motion. Impaired heel-to-toe progression was related to poor ankle range of motion in people with Multiple Sclerosis. Heel-to-toe progression provided a sensitive measure for assessing gait impairments that were not detectable using standard spatiotemporal gait parameters. Copyright © 2017 Elsevier Ltd. All rights reserved.

"Always looking for a new balance": toward an understanding of what it takes to continue working while being diagnosed with relapsing-remitting multiple sclerosis.

PubMed

Meide, Hanneke van der; Gorp, Dennis van; van der Hiele, Karin; Visser, Leo

2017-06-22

The aim of this study was to gain insight into the meaning of work in the everyday lives of people with relapsing-remitting multiple sclerosis, and the barriers and facilitators to staying in work. Nineteen employed adults diagnosed with relapsing-remitting multiple sclerosis participated in narrative interviews. All interviews were transcribed and coded for thematic analysis. For people with relapsing-remitting multiple sclerosis, continuing to work was a precarious balancing act. Five themes influenced this balance: becoming familiar with the disease, adjusting expectations, having an understanding and realistic line manager, seeing work as meaningful life activity and strategic considerations. People receiving a diagnosis of relapsing-remitting multiple sclerosis have to refamiliarize themselves with their own body in a meaningful way to be able to continue their work. Rehabilitation professionals can support them herein by taking into account not merely functional capabilities but also identity aspects of the body. Medication that stabilizes symptoms supports making the necessary adjustments. A trusting relationship with the line manager is vital for this adaptation process. Additionally, a match between being adequately challenged by work, while still having the capacity to meet those work demands, is needed, as is long-term financial stability. Implications for rehabilitation Rehabilitation professionals can support employees with relapsing-remitting multiple sclerosis by taking into account not merely functional capabilities but also identity aspects of the body. A trusting relationship with the line manager, including a timely disclosure of the diagnosis, is vital for people with relapsing-remitting multiple sclerosis to remain at work. For people with relapsing-remitting multiple sclerosis, there is a delicate balance between being adequately challenged by work while still having the capacity to meet work demands.

An ImmunoChip study of multiple sclerosis risk in African Americans

PubMed Central

Isobe, Noriko; Madireddy, Lohith; Khankhanian, Pouya; Matsushita, Takuya; Caillier, Stacy J.; Moré, Jayaji M.; Gourraud, Pierre-Antoine; McCauley, Jacob L.; Beecham, Ashley H.; Piccio, Laura; Herbert, Joseph; Khan, Omar; Cohen, Jeffrey; Stone, Lael; Santaniello, Adam; Cree, Bruce A. C.; Onengut-Gumuscu, Suna; Rich, Stephen S.; Hauser, Stephen L.; Sawcer, Stephen

2015-01-01

The aims of this study were: (i) to determine to what degree multiple sclerosis-associated loci discovered in European populations also influence susceptibility in African Americans; (ii) to assess the extent to which the unique linkage disequilibrium patterns in African Americans can contribute to localizing the functionally relevant regions or genes; and (iii) to search for novel African American multiple sclerosis-associated loci. Using the ImmunoChip custom array we genotyped 803 African American cases with multiple sclerosis and 1516 African American control subjects at 130 135 autosomal single nucleotide polymorphisms. We conducted association analysis with rigorous adjustments for population stratification and admixture. Of the 110 non-major histocompatibility complex multiple sclerosis-associated variants identified in Europeans, 96 passed stringent quality control in our African American data set and of these, >70% (69) showed over-representation of the same allele amongst cases, including 21 with nominally significant evidence for association (one-tailed test P < 0.05). At a further eight loci we found nominally significant association with an alternate correlated risk-tagging single nucleotide polymorphism from the same region. Outside the regions known to be associated in Europeans, we found seven potentially associated novel candidate multiple sclerosis variants (P < 10−4), one of which (rs2702180) also showed nominally significant evidence for association (one-tailed test P = 0.034) in an independent second cohort of 620 African American cases and 1565 control subjects. However, none of these novel associations reached genome-wide significance (combined P = 6.3 × 10−5). Our data demonstrate substantial overlap between African American and European multiple sclerosis variants, indicating common genetic contributions to multiple sclerosis risk. PMID:25818868

An ImmunoChip study of multiple sclerosis risk in African Americans.

PubMed

Isobe, Noriko; Madireddy, Lohith; Khankhanian, Pouya; Matsushita, Takuya; Caillier, Stacy J; Moré, Jayaji M; Gourraud, Pierre-Antoine; McCauley, Jacob L; Beecham, Ashley H; Piccio, Laura; Herbert, Joseph; Khan, Omar; Cohen, Jeffrey; Stone, Lael; Santaniello, Adam; Cree, Bruce A C; Onengut-Gumuscu, Suna; Rich, Stephen S; Hauser, Stephen L; Sawcer, Stephen; Oksenberg, Jorge R

2015-06-01

The aims of this study were: (i) to determine to what degree multiple sclerosis-associated loci discovered in European populations also influence susceptibility in African Americans; (ii) to assess the extent to which the unique linkage disequilibrium patterns in African Americans can contribute to localizing the functionally relevant regions or genes; and (iii) to search for novel African American multiple sclerosis-associated loci. Using the ImmunoChip custom array we genotyped 803 African American cases with multiple sclerosis and 1516 African American control subjects at 130 135 autosomal single nucleotide polymorphisms. We conducted association analysis with rigorous adjustments for population stratification and admixture. Of the 110 non-major histocompatibility complex multiple sclerosis-associated variants identified in Europeans, 96 passed stringent quality control in our African American data set and of these, >70% (69) showed over-representation of the same allele amongst cases, including 21 with nominally significant evidence for association (one-tailed test P < 0.05). At a further eight loci we found nominally significant association with an alternate correlated risk-tagging single nucleotide polymorphism from the same region. Outside the regions known to be associated in Europeans, we found seven potentially associated novel candidate multiple sclerosis variants (P < 10(-4)), one of which (rs2702180) also showed nominally significant evidence for association (one-tailed test P = 0.034) in an independent second cohort of 620 African American cases and 1565 control subjects. However, none of these novel associations reached genome-wide significance (combined P = 6.3 × 10(-5)). Our data demonstrate substantial overlap between African American and European multiple sclerosis variants, indicating common genetic contributions to multiple sclerosis risk. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Older age, higher perceived disability and depressive symptoms predict the amount and severity of work-related difficulties in persons with multiple sclerosis.

PubMed

Raggi, Alberto; Giovannetti, Ambra Mara; Schiavolin, Silvia; Brambilla, Laura; Brenna, Greta; Confalonieri, Paolo Agostino; Cortese, Francesca; Frangiamore, Rita; Leonardi, Matilde; Mantegazza, Renato Emilio; Moscatelli, Marco; Ponzio, Michela; Torri Clerici, Valentina; Zaratin, Paola; De Torres, Laura

2018-04-16

This cross-sectional study aims to identify the predictors of work-related difficulties in a sample of employed persons with multiple sclerosis as addressed with the Multiple Sclerosis Questionnaire for Job Difficulties. Hierarchical linear regression analysis was conducted to identify predictors of work difficulties: predictors included demographic variables (age, formal education), disease duration and severity, perceived disability and psychological variables (cognitive dysfunction, depression and anxiety). The targets were the questionnaire's overall score and its six subscales. A total of 177 participants (108 females, aged 21-63) were recruited. Age, perceived disability and depression were direct and significant predictors of the questionnaire total score, and the final model explained 43.7% of its variation. The models built on the questionnaire's subscales show that perceived disability and depression were direct and significant predictors of most of its subscales. Our results show that, among patients with multiple sclerosis, those who were older, with higher perceived disability and higher depression symptoms have more and more severe work-related difficulties. The Multiple Sclerosis Questionnaire for Job Difficulties can be fruitfully exploited to plan tailored actions to limit the likelihood of near-future job loss in persons of working age with multiple sclerosis. Implications for rehabilitation Difficulties with work are common among people with multiple sclerosis and are usually addressed in terms of unemployment or job loss. The Multiple Sclerosis Questionnaire for Job Difficulties is a disease-specific questionnaire developed to address the amount and severity of work-related difficulties. We found that work-related difficulties were associated to older age, higher perceived disability and depressive symptoms. Mental health issues and perceived disability should be consistently included in future research targeting work-related difficulties.

The multiple sclerosis work difficulties questionnaire: translation and cross-cultural adaptation to Turkish and assessment of validity and reliability.

PubMed

Kahraman, Turhan; Özdoğar, Asiye Tuba; Honan, Cynthia Alison; Ertekin, Özge; Özakbaş, Serkan

2018-05-09

To linguistically and culturally adapt the Multiple Sclerosis Work Difficulties Questionnaire-23 (MSWDQ-23) for use in Turkey, and to examine its reliability and validity. Following standard forward-back translation of the MSWDQ-23, it was administered to 124 people with multiple sclerosis (MS). Validity was evaluated using related outcome measures including those related to employment status and expectations, disability level, fatigue, walking, and quality of life. Randomly selected participants were asked to complete the MSWDQ-23 again to assess test-retest reliability. Confirmatory factor analysis on the MSWDQ-23 demonstrated a good fit for the data, and the internal consistency of each subscale was excellent. The test-retest reliability for the total score, psychological/cognitive barriers, physical barriers, and external barriers subscales were high. The MSWDQ-23 and its subscales were positively correlated with the employment, disability level, walking, and fatigue outcome measures. This study suggests that the Turkish version of MSWDQ-23 has high reliability and adequate validity, and it can be used to determine the difficulties faced by people with multiple sclerosis in workplace. Moreover, the study provides evidence about the test-retest reliability of the questionnaire. Implications for rehabilitation Multiple sclerosis affects young people of working age. Understanding work-related problems is crucial to enhance people with multiple sclerosis likelihood of maintaining their job. The Multiple Sclerosis Work Difficulties Questionnaire-23 (MSWDQ-23) is a valid and reliable measure of perceived workplace difficulties in people with multiple sclerosis: we presented its validation to Turkish. Professionals working in the field of vocational rehabilitation may benefit from using the MSWDQ-23 to predict the current work outcomes and future employment expectations.

The liminal self in people with multiple sclerosis: an interpretative phenomenological exploration of being diagnosed.

PubMed

Strickland, Karen; Worth, Allison; Kennedy, Catriona

2017-06-01

To explore the lived experience of the meaning of being diagnosed with multiple sclerosis on the individual's sense of self. The time leading up to and immediately following the diagnosis of multiple sclerosis has been identified as a time period shrouded by uncertainty and one where individuals have a heightened desire to seek accurate information and support. The diagnosis brings changes to the way one views the self which has consequences for biographical construction. A hermeneutic phenomenological study. In-depth qualitative interviews were conducted with 10 people recently diagnosed with multiple sclerosis. The data were analysed using interpretative phenomenological analysis. This study presents the three master themes: the 'road to diagnosis', 'the liminal self' and 'learning to live with multiple sclerosis'. The diagnosis of multiple sclerosis may be conceptualised as a 'threshold moment' where the individual's sense of self is disrupted from the former taken-for-granted way of being and propose a framework which articulates the transition. The findings highlight the need for healthcare professionals to develop interventions to better support people affected by a new diagnosis of multiple sclerosis. The conceptual framework which has been developed from the data and presented in this study provides a new way of understanding the impact of the diagnosis on the individual's sense of self when affected by a new diagnosis of multiple sclerosis. This framework can guide healthcare professionals in the provision of supportive care around the time of diagnosis. The findings provide practitioners with a new way of understanding the impact of the diagnosis on the individual's sense of self and a framework which can guide them in the provision of supportive care around the time of diagnosis. © 2016 John Wiley & Sons Ltd.

Anti-inflammatory nutritional intervention in patients with relapsing-remitting and primary-progressive multiple sclerosis: A pilot study

PubMed Central

Rossano, Rocco; Larocca, Marilena; Trotta, Vincenzo; Mennella, Ilario; Vitaglione, Paola; Ettorre, Michele; Graverini, Antonio; De Santis, Alessandro; Di Monte, Elisabetta; Coniglio, Maria Gabriella

2016-01-01

The aim of this work was to assess the influence of nutritional intervention on inflammatory status and wellness in people with multiple sclerosis. To this end, in a seven-month pilot study we investigated the effects of a calorie-restricted, semi-vegetarian diet and administration of vitamin D and other dietary supplements (fish oil, lipoic acid, omega-3 polyunsaturated fatty acids, resveratrol and multivitamin complex) in 33 patients with relapsing-remitting multiple sclerosis and 10 patients with primary-progressive multiple sclerosis. At 0/3/6 months, patients had neurological examination, filled questionnaires and underwent anthropometric measurements and biochemical analyses. Serum fatty acids and vitamin D levels were measured as markers of dietary compliance and nutritional efficacy of treatment, whereas serum gelatinase levels were analyzed as markers of inflammatory status. All patients had insufficient levels of vitamin D at baseline, but their values did not ameliorate following a weekly administration of 5000  IU, and rather decreased over time. Conversely, omega-3 polyunsaturated fatty acids increased already after three months, even under dietary restriction only. Co-treatment with interferon-beta in relapsing-remitting multiple sclerosis was irrelevant to vitamin D levels. After six months nutritional treatment, no significant changes in neurological signs were observed in any group. However, serum levels of the activated isoforms of gelatinase matrix metalloproteinase-9 decreased by 59% in primary-progressive multiple sclerosis and by 51% in relapsing-remitting multiple sclerosis patients under nutritional intervention, including dietary supplements. This study indicates that a healthy nutritional intervention is well accepted by people with multiple sclerosis and may ameliorate their physical and inflammatory status. PMID:26785711

Anti-inflammatory nutritional intervention in patients with relapsing-remitting and primary-progressive multiple sclerosis: A pilot study.

PubMed

Riccio, Paolo; Rossano, Rocco; Larocca, Marilena; Trotta, Vincenzo; Mennella, Ilario; Vitaglione, Paola; Ettorre, Michele; Graverini, Antonio; De Santis, Alessandro; Di Monte, Elisabetta; Coniglio, Maria Gabriella

2016-03-01

The aim of this work was to assess the influence of nutritional intervention on inflammatory status and wellness in people with multiple sclerosis. To this end, in a seven-month pilot study we investigated the effects of a calorie-restricted, semi-vegetarian diet and administration of vitamin D and other dietary supplements (fish oil, lipoic acid, omega-3 polyunsaturated fatty acids, resveratrol and multivitamin complex) in 33 patients with relapsing-remitting multiple sclerosis and 10 patients with primary-progressive multiple sclerosis. At 0/3/6 months, patients had neurological examination, filled questionnaires and underwent anthropometric measurements and biochemical analyses. Serum fatty acids and vitamin D levels were measured as markers of dietary compliance and nutritional efficacy of treatment, whereas serum gelatinase levels were analyzed as markers of inflammatory status. All patients had insufficient levels of vitamin D at baseline, but their values did not ameliorate following a weekly administration of 5000  IU, and rather decreased over time. Conversely, omega-3 polyunsaturated fatty acids increased already after three months, even under dietary restriction only. Co-treatment with interferon-beta in relapsing-remitting multiple sclerosis was irrelevant to vitamin D levels. After six months nutritional treatment, no significant changes in neurological signs were observed in any group. However, serum levels of the activated isoforms of gelatinase matrix metalloproteinase-9 decreased by 59% in primary-progressive multiple sclerosis and by 51% in relapsing-remitting multiple sclerosis patients under nutritional intervention, including dietary supplements. This study indicates that a healthy nutritional intervention is well accepted by people with multiple sclerosis and may ameliorate their physical and inflammatory status. © 2016 by the Society for Experimental Biology and Medicine.

Rhabdomyolysis following interferon-beta treatment in a patient with multiple sclerosis - A case report.

PubMed

Dalbjerg, Sara Maria; Tsakiri, Anna; Frederiksen, Jette Lautrup

2016-07-01

Multiple sclerosis is an inflammatory disease of the central nervous system for which there is currently no cure. Interferon-beta-1-alpha is worldwide one of the most widely used treatments in multiple sclerosis. To our knowledge there is one previous reported case of rhabdomyolysis associated with Interferon-beta treatment. We describe a 30 year old man with relapsing remitting multiple sclerosis who developed rhabdomyolysis and increased creatine kinase following Interferon-beta-1-alpha therapy. After the medication was discontinued, the patient rapidly improved. Clinicians should be aware of the possibility of rhabdomyolysis occurring during Interferon-beta-1-alpha therapy. In cases where patients complain of severe myalgia, and in particular if weakness is reported, creatine kinase activity should be measured to prevent irreversible rhabdomyolysis during Interferon-beta-1-alpha therapy in patients with multiple sclerosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Evolution of multiple sclerosis in France since the beginning of hepatitis B vaccination.

PubMed

Le Houézec, Dominique

2014-12-01

Since the implementation of the mass vaccination campaign against hepatitis B in France, the appearance of multiple sclerosis, sometimes occurring in the aftermath of vaccinations, led to the publication of epidemiological international studies. This was also justified by the sharp increase in the annual incidence of multiple sclerosis reported to the French health insurance in the mid-1990s. Almost 20 years later, a retrospective reflection can be sketched from these official data and also from the national pharmacovigilance agency. Statistical data from these latter sources seem to show a significant correlation between the number of hepatitis B vaccinations performed and the declaration to the pharmacovigilance of multiple sclerosis occurring between 1 and 2 years later. The application of the Hill's criteria to these data indicates that the correlation between hepatitis B vaccine and multiple sclerosis may be causal.

Latin American algorithm for treatment of relapsing-remitting multiple sclerosis using disease-modifying agents.

PubMed

Finkelsztejn, Alessandro; Gabbai, Alberto Alain; Fragoso, Yara Dadalti; Carrá, Adriana; Macías-Islas, Miguel Angel; Arcega-Revilla, Raul; García-Bonitto, Juan; Oehninger-Gatti, Carlos Luis; Orozco-Escobar, Geraldine; Tarulla, Adriana; Vergara, Fernando; Vizcarra, Darwin

2012-10-01

It is estimated that circa 50,000 individuals have relapsing-remitting multiple sclerosis in Latin America. European and North-American algorithms for the treatment of multiple sclerosis do not foresee our regional difficulties and the access of patients to treatment. The Latin American Multiple Sclerosis Forum is an independent and supra-institutional group of experts that has assessed the latest scientific evidence regarding efficacy and safety of disease-modifying treatments. Accesses to treatment and pharmacovigilance programs for each of the eight countries represented at the Forum were also analyzed. A specific set of guidelines based upon evidence-based recommendations was designed for Latin America. Future perspectives of multiple sclerosis treatment were also discussed. The present paper translated an effort from representatives of eight countries discussing a matter that cannot be adapted to our region directly from purely European and North-American guidelines for treatment.

The Practice of Sport in Multiple Sclerosis: Update.

PubMed

Donze, Cecile; Massot, Caroline; Hautecoeur, Patrick; Cattoir-Vue, Helene; Guyot, Marc-Alexandre

The practice of sport by multiple sclerosis patients has long been controversial. Recent studies, however, show that both sport and physical activity are essential for these patients. Indeed, they help to cope with the effects of multiple sclerosis, such as fatigue, reduced endurance, loss of muscle mass, and reduction of muscle strength. The beneficial effects of physical activity on these patients have been underlined in several studies, whereas those of practicing sport have been the subject of fewer evaluations and assessments. The aim of this update is to report on the effects of sport on multiple sclerosis patients. The benefits of sport have been demonstrated in several studies. It helps multiple sclerosis patients to increase their balance, resistance to fatigue, mobility and quality of life. Several biases in these studies do not enable us to recommend the practice of some of these sports on a routine basis.

Systematic review of depression in patients with multiple sclerosis and its relationship to interferonβ treatment.

PubMed

Alba Palé, Leila; León Caballero, Jordi; Samsó Buxareu, Berta; Salgado Serrano, Purificación; Pérez Solà, Víctor

2017-10-01

Multiple sclerosis is a chronic disease considered the major cause of neurological disability in young adults worldwide. While depression is considered a determinant factor of impaired quality of life and poorer prognosis among patients with multiple sclerosis, it is very often dismissed and undertreated by physicians. Depression has been related to treatment with some immunomodulatory drugs, such as IFNβ. Data from patients who committed suicide during the pivotal study of interferon used as a disease modifying treatment in multiple sclerosis support this association. Moreover, there is plenty of evidence of neuropsychiatric toxicity caused by the use of IFNα as a treatment for other medical conditions. Although this link still remains relatively unknown, the presence of warnings regarding the possible relationship between depression and IFNβ led to restriction in medical indications in these patients. The purpose of this paper is to try to understand the reasons for an increased prevalence in depression in multiple sclerosis and to examine the impact that IFNβ treatment has on their mood. We performed a literature search on MEDLINE and Google Scholar databases applying PRISMA guidelines for systematic reviews. Studies were included if the participants were diagnosed with MS and prescribed IFNβ as the main treatment. We excluded non-english and full-text non available papers, as well as the articles where mental health was assessed exclusively as a feature of quality of life. The sample includes articles from 1980 to 2014, although filtration by year of publication was not applied and contains data from IFNβ-1a and IFNβ-1b. The Cochrane Collaboration Tool assessing risk of bias was used to determine the quality of the studies. Ten studies met full criteria for inclusion and final data extraction. The articles have heterogeneity regarding the samples, the methodology used and the expression of the results. Only three studies support the evidence of a relationship between depression and interferon, which is statistically significant in some patients at the beginning of the treatment. They suggest that only patients on IFNβ treatment with a past history of depression may develop a major depression episode during the first six months. The remaining articles reviewed (including BENEFIT, BEYOND, and LTF trials) suggest the absence of an association. The reviewed studies conclude that there is not a clear relationship between IFNβ and depression. A history of depression is a risk factor for developing depression during the first 6 months of treatment, nevertheless, it is not sufficient to contraindicate it. The development of new strategies is crucial for early detection of depressive symptoms. An adequate treatment can both improve the mood and deal with the neurological disease by increasing treatment adherence and interfering with inflammation. Chronic destructive brain changes and serotonergic depletion due to inflammatory factors have been proposed as the underlying cause of depression in these patients. It is suggested that these patients would have fewer functional reserve remaining to deal with stressful life events, which could precipitate a depressive disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

A gradient in cortical pathology in multiple sclerosis by in vivo quantitative 7 T imaging

PubMed Central

Louapre, Céline; Govindarajan, Sindhuja T.; Giannì, Costanza; Nielsen, A. Scott; Cohen-Adad, Julien; Sloane, Jacob; Kinkel, Revere P.

2015-01-01

We used a surface-based analysis of T2* relaxation rates at 7 T magnetic resonance imaging, which allows sampling quantitative T2* throughout the cortical width, to map in vivo the spatial distribution of intracortical pathology in multiple sclerosis. Ultra-high resolution quantitative T2* maps were obtained in 10 subjects with clinically isolated syndrome/early multiple sclerosis (≤3 years disease duration), 18 subjects with relapsing-remitting multiple sclerosis (≥4 years disease duration), 13 subjects with secondary progressive multiple sclerosis, and in 17 age-matched healthy controls. Quantitative T2* maps were registered to anatomical cortical surfaces for sampling T2* at 25%, 50% and 75% depth from the pial surface. Differences in laminar quantitative T2* between each patient group and controls were assessed using general linear model (P < 0.05 corrected for multiple comparisons). In all 41 multiple sclerosis cases, we tested for associations between laminar quantitative T2*, neurological disability, Multiple Sclerosis Severity Score, cortical thickness, and white matter lesions. In patients, we measured, T2* in intracortical lesions and in the intracortical portion of leukocortical lesions visually detected on 7 T scans. Cortical lesional T2* was compared with patients’ normal-appearing cortical grey matter T2* (paired t-test) and with mean cortical T2* in controls (linear regression using age as nuisance factor). Subjects with multiple sclerosis exhibited relative to controls, independent from cortical thickness, significantly increased T2*, consistent with cortical myelin and iron loss. In early disease, T2* changes were focal and mainly confined at 25% depth, and in cortical sulci. In later disease stages T2* changes involved deeper cortical laminae, multiple cortical areas and gyri. In patients, T2* in intracortical and leukocortical lesions was increased compared with normal-appearing cortical grey matter (P < 10−10 and P < 10−7), and mean cortical T2* in controls (P < 10−5 and P < 10−6). In secondary progressive multiple sclerosis, T2* in normal-appearing cortical grey matter was significantly increased relative to controls (P < 0.001). Laminar T2* changes may, thus, result from cortical pathology within and outside focal cortical lesions. Neurological disability and Multiple Sclerosis Severity Score correlated each with the degree of laminar quantitative T2* changes, independently from white matter lesions, the greatest association being at 25% depth, while they did not correlate with cortical thickness and volume. These findings demonstrate a gradient in the expression of cortical pathology throughout stages of multiple sclerosis, which was associated with worse disability and provides in vivo evidence for the existence of a cortical pathological process driven from the pial surface. PMID:25681411

Systemic sclerosis and sarcoidosis: a rare case of chronic intestinal pseudo-obstruction.

PubMed

Bernardo, Sónia; Gonçalves, Ana Rita; Araújo-Correia, Luís

2018-06-01

The coexistence of systemic sclerosis (SSc) and sarcoidosis is an extremely rare phenomenon; some studies question its existence. We report the case of a male with a diagnosis of sarcoidosis that was admitted due to abdominal distension and pain. After a thorough investigation, he was diagnosed with severe chronic intestinal pseudo-obstruction as a manifestation of SSc.

76 FR 1568 - Special Local Regulations and Safety Zones; Recurring Events in Northern New England

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-11

..., 069[deg]31[min]29[sec] W;43[deg]52[min]09[sec] N, 069[deg]31[min]56[sec] W. 8.6 Multiple Sclerosis Event Type: Regatta and Sailboat Regatta. Race. Sponsor: Maine Chapter, Multiple Sclerosis Society. Date...]51[sec] W. 8.7 Multiple Sclerosis Event Type: Power Boat Race. Harborfest Tugboat Race. Sponsor...

76 FR 80850 - Special Local Regulations and Safety Zones; Recurring Events in Northern New England

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-27

...[deg]31'29'' W. 43[deg]52'09'' N, 069[deg]31'56'' W. 8.6 Multiple Sclerosis Regatta......... Event Type: Regatta and Sailboat Race. Sponsor: Maine Chapter, Multiple Sclerosis Society. Date: A one day event on..., 070[deg]13'51'' W. 8.7 Multiple Sclerosis Harborfest Event Type: Power Boat Tugboat Race. Race...

78 FR 47555 - Special Local Regulations and Safety Zones; Recurring Events in Northern New England

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-06

...]52'35'' N, 069[deg]31'29'' W. 43[deg]52'09'' N, 069[deg]31'56'' W. 8.6 Multiple Sclerosis Regatta......... Event Type: Regatta and Sailboat Race. Sponsor: Maine Chapter, Multiple Sclerosis Society. Date: A one..., National Multiple Sclerosis Society. Date: A one day event on the third Sunday of August.* Time...

Multiple sclerosis: Left advantage for auditory laterality in dichotic tests of central auditory processing and relationship of psychoacoustic tests with the Multiple Sclerosis Disability Scale-EDSS.

PubMed

Peñaloza López, Yolanda Rebeca; Orozco Peña, Xóchitl Daisy; Pérez Ruiz, Santiago Jesús

2018-04-03

To evaluate the central auditory processing disorders in patients with multiple sclerosis, emphasizing auditory laterality by applying psychoacoustic tests and to identify their relationship with the Multiple Sclerosis Disability Scale (EDSS) functions. Depression scales (HADS), EDSS, and 9 psychoacoustic tests to study CAPD were applied to 26 individuals with multiple sclerosis and 26 controls. Correlation tests were performed between the EDSS and psychoacoustic tests. Seven out of 9 psychoacoustic tests were significantly different (P<.05); right or left (14/19 explorations) with respect to control. In dichotic digits there was a left-ear advantage compared to the usual predominance of RDD. There was significant correlation in five psychoacoustic tests and the specific functions of EDSS. The left-ear advantage detected and interpreted as an expression of deficient influences of the corpus callosum and attention in multiple sclerosis should be investigated. There was a correlation between psychoacoustic tests and specific EDSS functions. Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.

Stress and multiple sclerosis: A systematic review considering potential moderating and mediating factors and methods of assessing stress.

PubMed

Briones-Buixassa, Laia; Milà, Raimon; Mª Aragonès, Josep; Bufill, Enric; Olaya, Beatriz; Arrufat, Francesc Xavier

2015-07-01

Research about the effects of stress on multiple sclerosis has yielded contradictory results. This study aims to systematically review the evidence focusing on two possible causes: the role of stress assessment and potential moderating and mediating factors. The Web of Knowledge (MEDLINE and Web of Science), Scopus, and PsycINFO databases were searched for relevant articles published from 1900 through December 2014 using the terms "stress*" AND "multiple sclerosis." Twenty-three articles were included. Studies focused on the effect of stress on multiple sclerosis onset ( n  = 9) were mostly retrospective, and semi-structured interviews and scales yielded the most consistent associations. Studies focused on multiple sclerosis progression ( n  = 14) were mostly prospective, and self-reported diaries yielded the most consistent results. The most important modifying factors were stressor duration, severity, and frequency; cardiovascular reactivity and heart rate; and social support and escitalopram intake. Future studies should consider the use of prospective design with self-reported evaluations and the study of moderators and mediators related to amount of stress and autonomic nervous system reactivity to determine the effects of stress on multiple sclerosis.

Stress and multiple sclerosis: A systematic review considering potential moderating and mediating factors and methods of assessing stress

PubMed Central

Briones-Buixassa, Laia; Milà, Raimon; Mª Aragonès, Josep; Bufill, Enric; Olaya, Beatriz; Arrufat, Francesc Xavier

2015-01-01

Research about the effects of stress on multiple sclerosis has yielded contradictory results. This study aims to systematically review the evidence focusing on two possible causes: the role of stress assessment and potential moderating and mediating factors. The Web of Knowledge (MEDLINE and Web of Science), Scopus, and PsycINFO databases were searched for relevant articles published from 1900 through December 2014 using the terms “stress*” AND “multiple sclerosis.” Twenty-three articles were included. Studies focused on the effect of stress on multiple sclerosis onset (n = 9) were mostly retrospective, and semi-structured interviews and scales yielded the most consistent associations. Studies focused on multiple sclerosis progression (n = 14) were mostly prospective, and self-reported diaries yielded the most consistent results. The most important modifying factors were stressor duration, severity, and frequency; cardiovascular reactivity and heart rate; and social support and escitalopram intake. Future studies should consider the use of prospective design with self-reported evaluations and the study of moderators and mediators related to amount of stress and autonomic nervous system reactivity to determine the effects of stress on multiple sclerosis. PMID:28070374

Vision and vision-related outcome measures in multiple sclerosis

PubMed Central

Balcer, Laura J.; Miller, David H.; Reingold, Stephen C.

2015-01-01

Visual impairment is a key manifestation of multiple sclerosis. Acute optic neuritis is a common, often presenting manifestation, but visual deficits and structural loss of retinal axonal and neuronal integrity can occur even without a history of optic neuritis. Interest in vision in multiple sclerosis is growing, partially in response to the development of sensitive visual function tests, structural markers such as optical coherence tomography and magnetic resonance imaging, and quality of life measures that give clinical meaning to the structure-function correlations that are unique to the afferent visual pathway. Abnormal eye movements also are common in multiple sclerosis, but quantitative assessment methods that can be applied in practice and clinical trials are not readily available. We summarize here a comprehensive literature search and the discussion at a recent international meeting of investigators involved in the development and study of visual outcomes in multiple sclerosis, which had, as its overriding goals, to review the state of the field and identify areas for future research. We review data and principles to help us understand the importance of vision as a model for outcomes assessment in clinical practice and therapeutic trials in multiple sclerosis. PMID:25433914

Can we prevent or treat multiple sclerosis by individualised vitamin D supply?

PubMed Central

2013-01-01

Apart from its principal role in bone metabolism and calcium homeostasis, vitamin D has been attributed additional effects including an immunomodulatory, anti-inflammatory, and possibly even neuroprotective capacity which implicates a possible role of vitamin D in autoimmune diseases like multiple sclerosis (MS). Indeed, several lines of evidence including epidemiologic, preclinical, and clinical data suggest that reduced vitamin D levels and/or dysregulation of vitamin D homeostasis is a risk factor for the development of multiple sclerosis on the one hand, and that vitamin D serum levels are inversely associated with disease activity and progression on the other hand. However, these data are not undisputable, and many questions regarding the preventive and therapeutic capacity of vitamin D in multiple sclerosis remain to be answered. In particular, available clinical data derived from interventional trials using vitamin D supplementation as a therapeutic approach in MS are inconclusive and partly contradictory. In this review, we summarise and critically evaluate the existing data on the possible link between vitamin D and multiple sclerosis in light of the crucial question whether optimization of vitamin D status may impact the risk and/or the course of multiple sclerosis. PMID:23356351

Chronic restraint stress during early Theiler’s virus infection exacerbates the subsequent demyelinating disease in SJL mice: II. CNS disease severity

PubMed Central

Young, Erin E.; Sieve, Amy N.; Vichaya, Elisabeth G.; Carcoba, Luis M.; Young, Colin R.; Ambrus, Andrew; Storts, Ralph; Welsh, C. Jane R.; Meagher, Mary W.

2010-01-01

Theiler’s murine encephalomyelitis virus (TMEV) infection is a well-characterized model of multiple sclerosis (MS). Previous research has shown that chronic restraint stress (RS) during early TMEV infection exacerbates behavioral signs of disease. The present data suggest RS-induced increases in CNS inflammation, demyelination, and axonal degeneration may underlie this exacerbation. In addition, we report that males exhibit greater CNS inflammation and higher numbers of demyelinating lesions while females show greater susceptibility to RS-induced exacerbation. These findings indicate RS during early TMEV infection increases CNS lesion formation during the late phase and suggest the effects of RS are sex-dependent. PMID:20167380

Functional identification of pathogenic autoantibody responses in patients with multiple sclerosis

PubMed Central

Elliott, Christina; Lindner, Maren; Arthur, Ariel; Brennan, Kathryn; Jarius, Sven; Hussey, John; Chan, Andrew; Stroet, Anke; Olsson, Tomas; Willison, Hugh; Barnett, Susan C.; Meinl, Edgar

2012-01-01

Pathological and clinical studies implicate antibody-dependent mechanisms in the immunopathogenesis of multiple sclerosis. We tested this hypothesis directly by investigating the ability of patient-derived immunoglobulins to mediate demyelination and axonal injury in vitro. Using a myelinating culture system, we developed a sensitive and reproducible bioassay to detect and quantify these effects and applied this to investigate the pathogenic potential of immunoglobulin G preparations obtained from patients with multiple sclerosis (n = 37), other neurological diseases (n = 10) and healthy control donors (n = 13). This identified complement-dependent demyelinating immunoglobulin G responses in approximately 30% of patients with multiple sclerosis, which in two cases was accompanied by significant complement-dependent antibody mediated axonal loss. No pathogenic immunoglobulin G responses were detected in patients with other neurological disease or healthy controls, indicating that the presence of these demyelinating/axopathic autoantibodies is specific for a subset of patients with multiple sclerosis. Immunofluorescence microscopy revealed immunoglobulin G preparations with demyelinating activity contained antibodies that specifically decorated the surface of myelinating oligodendrocytes and their contiguous myelin sheaths. No other binding was observed indicating that the response is restricted to autoantigens expressed by terminally differentiated myelinating oligodendrocytes. In conclusion, our study identifies axopathic and/or demyelinating autoantibody responses in a subset of patients with multiple sclerosis. This observation underlines the mechanistic heterogeneity of multiple sclerosis and provides a rational explanation why some patients benefit from antibody depleting treatments. PMID:22561643

No evidence for an effect on brain atrophy rate of atorvastatin add-on to interferon β1b therapy in relapsing-remitting multiple sclerosis (the ARIANNA study).

PubMed

Lanzillo, Roberta; Quarantelli, Mario; Pozzilli, Carlo; Trojano, Maria; Amato, Maria Pia; Marrosu, Maria G; Francia, Ada; Florio, Ciro; Orefice, Giuseppe; Tedeschi, Gioacchino; Bellantonio, Paolo; Annunziata, Pasquale; Grimaldi, Luigi M; Comerci, Marco; Brunetti, Arturo; Bonavita, Vincenzo; Alfano, Bruno; Marini, Stefano; Brescia Morra, Vincenzo

2016-08-01

A previous phase 2 trial has suggested that statins might delay brain atrophy in secondary progressive multiple sclerosis. The objective of this study was to evaluate the effect of atorvastatin add-on therapy on cerebral atrophy in relapsing-remitting multiple sclerosis. This randomised, placebo-controlled study compared atorvastatin 40 mg or placebo add-on therapy to interferon β1b for 24 months. Brain magnetic resonance imaging, multiple sclerosis functional composite score, Rao neuropsychological battery and expanded disability status scale were evaluated over 24 months. A total of 154 patients were randomly assigned, 75 in the atorvastatin and 79 in the placebo arms, with a comparable drop-out rate (overall 23.4%). Brain atrophy over 2 years was not different in the two arms (-0.38% and -0.32% for the atorvastatin and placebo groups, respectively). Relapse rate, expanded disability status scale, multiple sclerosis functional composite score or cognitive changes were not different in the two arms. Patients withdrawing from the study had a higher number of relapses in the previous 2 years (P=0.04) and a greater probability of relapsing within 12 months. Our results suggest that the combination of atorvastatin and interferon β1b is not justified in early relapsing-remitting multiple sclerosis and adds to the body of evidence indicating an absence of significant radiological and clinical benefit of statins in relapsing-remitting multiple sclerosis. © The Author(s), 2015.

Correlation between white matter damage and gray matter lesions in multiple sclerosis patients.

PubMed

Han, Xue-Mei; Tian, Hong-Ji; Han, Zheng; Zhang, Ce; Liu, Ying; Gu, Jie-Bing; Bakshi, Rohit; Cao, Xia

2017-05-01

We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. We analyzed the correlation between fractional anisotropy values and changes in whole-brain gray matter volume. The participants included 20 patients with relapsing-remitting multiple sclerosis and 20 healthy volunteers as controls. All subjects underwent head magnetic resonance imaging and diffusion tensor imaging. Our results revealed that fractional anisotropy values decreased and gray matter volumes were reduced in the genu and splenium of corpus callosum, left anterior thalamic radiation, hippocampus, uncinate fasciculus, right corticospinal tract, bilateral cingulate gyri, and inferior longitudinal fasciculus in multiple sclerosis patients. Gray matter volumes were significantly different between the two groups in the right frontal lobe (superior frontal, middle frontal, precentral, and orbital gyri), right parietal lobe (postcentral and inferior parietal gyri), right temporal lobe (caudate nucleus), right occipital lobe (middle occipital gyrus), right insula, right parahippocampal gyrus, and left cingulate gyrus. The voxel sizes of atrophic gray matter positively correlated with fractional anisotropy values in white matter association fibers in the patient group. These findings suggest that white matter fiber bundles are extensively injured in multiple sclerosis patients. The main areas of gray matter atrophy in multiple sclerosis are the frontal lobe, parietal lobe, caudate nucleus, parahippocampal gyrus, and cingulate gyrus. Gray matter atrophy is strongly associated with white matter injury in multiple sclerosis patients, particularly with injury to association fibers.

GWI-98 Relationships of Stress Exposures to Health in Gulf War Veterans

DTIC Science & Technology

1999-10-01

achieved by obtaining in-depth data from a national sample of GW veterans, including both men and women in active and reserve components. The design...LIVER DISEASE LUPUS , THYROID DISEASE, OR OTHER AUTOIMMUNE DISORDERS MULTIPLE SCLEROSIS, EPILEPSY, OR OTHER NEUROLOGICAL DISORDERS CHRONIC STOMACH OR...114. How many of the women or men you knew, or were close to, were killed, wounded, or MIA? From time entered until 8/90 0=NEVER 1=1 TIME 2=2

Multiple Sclerosis Epidemiology in East Asia, South East Asia and South Asia: A Systematic Review.

PubMed

Eskandarieh, Sharareh; Heydarpour, Pouria; Minagar, Alireza; Pourmand, Shadi; Sahraian, Mohammad Ali

2016-01-01

Multiple sclerosis (MS) is one of the most common chronic immune-mediated diseases of the human central nervous system and an important cause of non-traumatic neurologic disability among young population in several countries. Recent reports from East Asia, South East Asia and South Asia have proposed a low to moderate prevalence of MS in these countries. A literature review search was carried out in December 2014 in Medline, Embase, Scopus and Cochrane library to recover original population-based studies on MS epidemiology in East Asia, South East Asia and South Asia countries published between January 1, 1950 and December 30, 2014. We intended search strategies using the key words: multiple sclerosis, prevalence, incidence and epidemiology. Based on our inclusion criteria, 68 epidemiologic studies were included in this systematic review. The most extensively used diagnostic criteria in the studies were McDonald's criteria. Most studies were performed in a multi-center hospital setting. The female to male ratio varied and ranged from 0.7 in India to 9.0 in China. The mean age at disease onset ranged from the lowest age of 25.3 in Iran to the highest age of 46.4 in China. MS prevalence ranged from 0.77 in 100,000 populations in Hong Kong (1999) to 85.80 in 100,000 in Iran (2013). Advances in MS registries around the globe allow nationwide population-based studies and will allow worldly comparisons between the prevalence and incidence in different regions that are provided to monitor estimation. © 2016 S. Karger AG, Basel.

Biome depletion in conjunction with evolutionary mismatches could play a role in the etiology of neurofibromatosis 1.

PubMed

Beales, Donna L

2015-04-01

Neurofibromatosis 1 (NF1) arises de novo in a striking 30-50% of cases, pointing toward an environmental etiology, though none has been clearly identified. The Biome Depletion Theory posits that the absence of mutualistic and commensal organisms within the human body coupled with modern lifestyle alterations may have profoundly deleterious effects, inclusive of immunologic derangement that is thought to result in allergy, atopy, and numerous autoimmune diseases. Biome depletion has been implicated as a factor in the etiology of both multiple sclerosis and autism spectrum disorders; biome reconstitution, i.e. replenishment of the biome with certain keynote species, is being used in the treatment of these and other autoimmune states. Neurofibromatosis 1 has been associated with allergy, various autoimmune states, multiple sclerosis, and autism. Recent research has posited that NF1, multiple sclerosis and autism may all arise from disturbances in the neural crest during gestation. This paper hypothesizes that there is indirect evidence that a highly inflammatory uterine state may precipitate epigenetic changes in vulnerable NF-related genes in the course of fetal development. The etiology of NF1 may lie in the absence of immunomodulation by commensal and mutualistic species once ubiquitously present in the environment, as well as through adoption of a modern lifestyle that contributes to chronic inflammation. Replenishment of helminths and other missing organisms to the human biome prior to conception as well as addressing nutritional status, psychological stress, and environmental exposures may prevent the development of NF1. Copyright © 2015 Elsevier Ltd. All rights reserved.

Achieving patient engagement in multiple sclerosis: A perspective from the multiple sclerosis in the 21st Century Steering Group.

PubMed

Rieckmann, Peter; Boyko, Alexey; Centonze, Diego; Elovaara, Irina; Giovannoni, Gavin; Havrdová, Eva; Hommes, Otto; Kesselring, Jurg; Kobelt, Gisela; Langdon, Dawn; LeLorier, Jacques; Morrow, Sarah A; Oreja-Guevara, Celia; Schippling, Sven; Thalheim, Christoph; Thompson, Heidi; Vermersch, Patrick

2015-05-01

While advances in medicine, technology and healthcare services offer promises of longevity and improved quality of life (QoL), there is also increasing reliance on a patient׳s skills and motivation to optimize all the benefits available. Patient engagement in their own healthcare has been described as the 'blockbuster drug of the century'. In multiple sclerosis (MS), patient engagement is vital if outcomes for the patient, society and healthcare systems are to be optimized. The MS in the 21st Century Steering Group devised a set of themes that require action with regard to patient engagement in MS, namely: 1) setting and facilitating engagement by education and confidence-building; 2) increasing the importance placed on QoL and patient concerns through patient-reported outcomes (PROs); 3) providing credible sources of accurate information; 4) encouraging treatment adherence through engagement; and 5) empowering through a sense of responsibility. Group members independently researched and contributed examples of patient engagement strategies from several countries and examined interventions that have worked well in areas of patient engagement in MS, and other chronic illnesses. The group presents their perspective on these programs, discusses the barriers to achieving patient engagement, and suggests practical strategies for overcoming these barriers. With an understanding of the issues that influence patient engagement in MS, we can start to investigate ways to enhance engagement and subsequent health outcomes. Engaging patients involves a broad, multidisciplinary approach. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Low DPP4 expression and activity in multiple sclerosis.

PubMed

Tejera-Alhambra, Marta; Casrouge, Armanda; de Andrés, Clara; Ramos-Medina, Rocío; Alonso, Bárbara; Vega, Janet; Albert, Matthew L; Sánchez-Ramón, Silvia

2014-02-01

Multiple sclerosis (MS) is a prototypic Th1/Th17 chronic autoimmune disease of the central nervous system. Dipeptidyl peptidase 4 (DPP4 or CD26) is a multifunctional molecule involved in autoimmune diseases' pathophysiology. We sought to integrate disparate pieces of data and analyze the plasma levels of sDPP4, DPP activity and DPP4 surface expression on T-cells in 129 MS patients with different clinical forms and 53 healthy controls, across two independent cohorts. Herein, we provide new evidence that sDPP4 concentration and DPP activity are significantly lower in MS patients than controls (p < 0.0001 and p < 0.01, respectively). In contrast, the frequency of circulating CD8(+)DPP4(hi) T-cells (p = 0.02) was increased in MS patients. This is the first study that simultaneously analyzes DPP4 expression and function in a large cohort of MS patients. Our data indicate a putative role for DPP4 in MS pathophysiology and suggest that a deeper understanding of surface versus shed DPP4 biology is warranted. Copyright © 2013 Elsevier Inc. All rights reserved.

Graph Theoretical Framework of Brain Networks in Multiple Sclerosis: A Review of Concepts.

PubMed

Fleischer, Vinzenz; Radetz, Angela; Ciolac, Dumitru; Muthuraman, Muthuraman; Gonzalez-Escamilla, Gabriel; Zipp, Frauke; Groppa, Sergiu

2017-11-01

Network science provides powerful access to essential organizational principles of the human brain. It has been applied in combination with graph theory to characterize brain connectivity patterns. In multiple sclerosis (MS), analysis of the brain networks derived from either structural or functional imaging provides new insights into pathological processes within the gray and white matter. Beyond focal lesions and diffuse tissue damage, network connectivity patterns could be important for closely tracking and predicting the disease course. In this review, we describe concepts of graph theory, highlight novel issues of tissue reorganization in acute and chronic neuroinflammation and address pitfalls with regard to network analysis in MS patients. We further provide an outline of functional and structural connectivity patterns observed in MS, spanning from disconnection and disruption on one hand to adaptation and compensation on the other. Moreover, we link network changes and their relation to clinical disability based on the current literature. Finally, we discuss the perspective of network science in MS for future research and postulate its role in the clinical framework. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Factors that influence the employment status of people with multiple sclerosis: a multi-national study.

PubMed

Messmer Uccelli, M; Specchia, C; Battaglia, M A; Miller, D M

2009-12-01

Paid employment is valuable for society and for the individual. A diagnosis of a chronic illness such as multiple sclerosis (MS) can influence a person's employment status. Previous studies have reported that demographic and disease-related aspects can predict whether a person with MS will leave their job. The aim of the study was to assess the factors that people with MS believe to contribute to their employment status and to determine whether any of these differentiate people with MS who are employed from those who are not employed. A multinational questionnaire assessed aspects related to employment that facilitate or hinder job maintenance. Data was collected in 18 European countries. A total of 1,141 questionnaires were completed. Of those responding, 694 (61%) subjects were employed and 477 (39%) were unemployed. The items that significantly differentiated the groups were related to MS symptoms, workplace environment and financial considerations. While MS influences employment status for many people who face difficult symptoms, aspects like a flexible work schedule and financial security are important and perhaps key to promoting job maintenance among people with MS.

Complementary and alternative medicine for the treatment of multiple sclerosis

PubMed Central

Yadav, Vijayshree; Shinto, Lynne; Bourdette, Dennis

2010-01-01

Multiple sclerosis (MS) is a chronic disabling disease of the CNS that affects people during early adulthood. Despite several US FDA-approved medications, the treatment options in MS are limited. Many people with MS explore complementary and alternative medicine (CAM) treatments to help control their MS and treat their symptoms. Surveys suggest that up to 70% of people with MS have tried one or more CAM treatment for their MS. People with MS using CAM generally report deriving some benefit from the therapies. The CAM therapies most frequently used include diet, omega-3 fatty acids and antioxidants. There is very limited research evaluating the safety and effectiveness of CAM in MS. The most promising among CAM therapies that warrant further investigation are a low-fat diet, omega-3 fatty acids, lipoic acid and vitamin D supplementation as potential anti-inflammatory and neuroprotective agents in both relapsing and progressive forms of MS. There is very limited research evaluating the safety and effectiveness of CAM in MS. However, in recent years, the NIH and the National MS Society have been actively supporting the research in this very important area. PMID:20441425

Effect of fish oil on glutathione redox system in multiple sclerosis

PubMed Central

Sorto-Gomez, Tania E; Ortiz, Genaro G; Pacheco-Moises, Fermín P; Torres-Sanchez, Erandis D; Ramirez-Ramirez, Viridiana; Macias-Islas, Miguel A; de la Rosa, Alfredo Celis; Velázquez-Brizuela, Irma E

2016-01-01

Multiple sclerosis (MS) is a chronic, inflammatory and autoimmune disease of the central nervous system. Dysregulation of glutathione homeostasis and alterations in glutathione-dependent enzyme activities are implicated in the induction and progression of MS. Evidence suggests that Omega-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory, antioxidant and neuroprotective effects. The aim of the present work was to evaluate the effect of fish oil on the activity of glutathione reductase (GR), content of reduced and oxidized glutathione, and GSH/GSSG ratio in MS. 50 patients with relapsing-remitting MS were enrolled. The experimental group received orally 4 g/day of fish oil for 12 months. Fish oil supplementation resulted in a significant increase in n-3 fatty acids and a decrease n-6 fatty acids. No differences in glutathione reductase activity, content of reduced and oxidized glutathione, and GSH/GSSG ratio were found. Conclusion: Glutathione reductase activity was not significantly different between the groups; however, fish oil supplementation resulted in smaller increase in GR compared with control group, suggesting a possible effect on antioxidant defence mechanisms. PMID:27335704

Brain stem and cerebellar atrophy in chronic progressive neuro-Behçet's disease.

PubMed

Kanoto, Masafumi; Hosoya, Takaaki; Toyoguchi, Yuuki; Oda, Atsuko

2013-01-01

Chronic progressive neuro-Behçet's disease (CPNBD) resembles multiple sclerosis (MS) on patient background and image findings, and therefore is difficult to diagnose. The purpose is to identify the characteristic magnetic resonance imaging (MRI) findings of CPNBD and to clarify the differences between the MRI findings of CPNBD and those of MS. The subjects consist of a CPNBD group (n=4; 1 male and 3 females; mean age, 51 y.o.), a MS group (n=19; 3 males and 16 females; mean age, 45 y.o.) and a normal control group (n=23; 10 males and 13 females; mean age, 45 y.o.). Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were retrospectively evaluated in each subjects. In middle sagittal brain MR images, the prepontine distance was measured as an indirect index of brain stem and cerebellar atrophy and the pontine and mesencephalic distance was measured as a direct index of brain stem atrophy. These indexes were statistically analyzed. Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were seen in all CPNBD cases. Prepontine distance was significantly different between the CPNBD group and the MS group (p<0.05), and between the CPNBD group and the normal control group (p<0.001). Pontine and mesencephalic distance were significantly different between the CPNBD group and the MS group (p<0.001, p<0.01 respectively), and between the CPNBD group and the normal control group (p<0.001). Chronic progressive neuro-Behçet's disease should be considered in patients with brain stem and cerebellar atrophy in addition to leukoencephalopathy similar to that seen in multiple sclerosis. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Improving the quality of depression and pain care in multiple sclerosis using collaborative care: The MS-care trial protocol.

PubMed

Ehde, Dawn M; Alschuler, Kevin N; Sullivan, Mark D; Molton, Ivan P; Ciol, Marcia A; Bombardier, Charles H; Curran, Mary C; Gertz, Kevin J; Wundes, Annette; Fann, Jesse R

2018-01-01

Evidence-based pharmacological and behavioral interventions are often underutilized or inaccessible to persons with multiple sclerosis (MS) who have chronic pain and/or depression. Collaborative care is an evidence-based patient-centered, integrated, system-level approach to improving the quality and outcomes of depression care. We describe the development of and randomized controlled trial testing a novel intervention, MS Care, which uses a collaborative care model to improve the care of depression and chronic pain in a MS specialty care setting. We describe a 16-week randomized controlled trial comparing the MS Care collaborative care intervention to usual care in an outpatient MS specialty center. Eligible participants with chronic pain of at least moderate intensity (≥3/10) and/or major depressive disorder are randomly assigned to MS Care or usual care. MS Care utilizes a care manager to implement and coordinate guideline-based medical and behavioral treatments with the patient, clinic providers, and pain/depression treatment experts. We will compare outcomes at post-treatment and 6-month follow up. We hypothesize that participants randomly assigned to MS Care will demonstrate significantly greater control of both pain and depression at post-treatment (primary endpoint) relative to those assigned to usual care. Secondary analyses will examine quality of care, patient satisfaction, adherence to MS care, and quality of life. Study findings will aid patients, clinicians, healthcare system leaders, and policy makers in making decisions about effective care for pain and depression in MS healthcare systems. (PCORI- IH-1304-6379; clinicaltrials.gov: NCT02137044). This trial is registered at ClinicalTrials.gov, protocol NCT02137044. Copyright © 2017 Elsevier Inc. All rights reserved.

Potential treatment mechanisms in a mindfulness-based intervention for people with progressive multiple sclerosis.

PubMed

Bogosian, Angeliki; Hughes, Alicia; Norton, Sam; Silber, Eli; Moss-Morris, Rona

2016-11-01

To explore putative mediators of a mindfulness-based intervention to decrease distress in people with multiple sclerosis (MS) and to explore the patients' perspectives on this intervention. We used an explanatory mixed methods design incorporating quantitative data from a pilot randomized control trial and a qualitative interview study with people who completed the mindfulness intervention. People with MS (n = 40) completed standardized measures of distress (outcome), and acceptance, decentring, self-compassion, and self-efficacy (potential mediators). Semi-structured interviews (n = 15) of patients' experiences of the mindfulness intervention were analysed deductively and inductively. Decentring post-intervention explained 13% of the 3-month change in distress and between 27% and 31% of concurrent changes in distress. Acceptance changed only slightly, and as a result, the indirect effect accounts for only 2% of future distress and between 3% and 11% of concurrent distress. Qualitative data showed that acceptance and self-compassion needed more time to develop, whereas decentring could be implemented readily after being introduced in the sessions. Self-efficacy also had a large mediating effect. Participants in their interviews talked about group dynamics and prior expectations as essential elements that determine their engagement with the course and their level of satisfaction. Mindfulness interventions for people with a chronic progressive condition may benefit from focusing on helping them to accept daily challenges and teach them to recognize their thoughts and feelings, allowing time for acceptance and self-compassion to develop. Group dynamics also play a fundamental role in the success of the mindfulness interventions. Statement of Contribution What is already known on this subject? Mindfulness courses improve psychological well-being for people with chronic conditions. Mindfulness courses have been successful in improving psychological well-being and symptom management for people with multiple sclerosis but we do not know how these courses work. What does this study add? Decentering and self-efficacy appear to be key mechanisms leading to reduced distress. Acceptance and self-compassion may need more time and practice to develop. Group dynamics and expectations of the mindfulness courses were also important elements of mindfulness. © 2016 The British Psychological Society.

Exercising away the blues: can it help multiple sclerosis-related depression?

PubMed

Feinstein, Anthony; Rector, Neil; Motl, Robert

2013-12-01

The present review focuses on exercise as a treatment for depression in multiple sclerosis. While exercise has emerged as a potentially useful treatment in the general psychiatry-depression literature, the findings from a small number of multiple sclerosis-related treatment trials are equivocal. Methodological limitations, including the absence of depression as a primary endpoint, characterize all the studies completed to date. Given that limitations in study design can be rectified, it is time to put exercise to the test once more. Depressed multiple sclerosis patients and those involved in their care are looking for guidance here because the prevailing zeitgeist promotes the benefits of exercise to mood. But first, some clarity is needed.

Azathioprine therapy in a case of pediatric multiple sclerosis that was seropositive for MOG-IgG.

PubMed

Zhou, Yifan; Huang, Qiao; Lu, Tingting; Sun, Xiaobo; Fang, Ling; Lu, Zhengqi; Hu, Xueqiang; Kermode, Allan; Qiu, Wei

2017-04-01

There is a lack of evidence for treatment of pediatric multiple sclerosis (PedMS). Treatment using azathioprine for PedMS has not been reported. A 10-year-old boy with multiple sclerosis who was seropositive for antibodies against myelin oligodendrocyte glycoprotein (MOG)-IgG was treated with azathioprine plus oral methylprednisolone. The patient showed clinical and magnetic resonance imaging stability, with MOG-IgG seroconversion. There were no major side effects over a 5-year period. Azathioprine may be a treatment option, particularly in poor medical resource areas, for pediatric patients with multiple sclerosis who are seropositive for MOG-IgG. Copyright © 2017 Elsevier Ltd. All rights reserved.

Most Scottish neurologists do not apply the 2010 McDonald criteria when diagnosing multiple sclerosis.

PubMed

Lumley, R; Davenport, R; Williams, A

2015-03-01

The diagnostic criteria for multiple sclerosis have evolved over time and currently the 2010 McDonald criteria are the most widely accepted. These criteria allow the diagnosis of multiple sclerosis to be made at the clinically isolated syndrome stage provided certain criteria are met on a single magnetic resonance brain scan. Our hypothesis was that neurologists in Scotland did not use these criteria routinely. We sent a SurveyMonkey questionnaire to all Scottish neurologists (consultants and trainees) regarding the diagnosis of multiple sclerosis. Our questionnaire response rate was 65/99 (66%). Most Scottish neurologists were aware of the criteria and 31/58 (53%) felt that they were using these routinely. However, in a clinical vignette designed to test the application of these criteria, only 5/57 (9%) of neurologists appeared to use them. Scottish neurologists' use of the 2010 McDonald criteria for diagnosis of multiple sclerosis varies from practitioners' perception of their use of these criteria.

Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

PubMed Central

Beecham, Ashley H; Patsopoulos, Nikolaos A; Xifara, Dionysia K; Davis, Mary F; Kemppinen, Anu; Cotsapas, Chris; Shahi, Tejas S; Spencer, Chris; Booth, David; Goris, An; Oturai, Annette; Saarela, Janna; Fontaine, Bertrand; Hemmer, Bernhard; Martin, Claes; Zipp, Frauke; D’alfonso, Sandra; Martinelli-Boneschi, Filippo; Taylor, Bruce; Harbo, Hanne F; Kockum, Ingrid; Hillert, Jan; Olsson, Tomas; Ban, Maria; Oksenberg, Jorge R; Hintzen, Rogier; Barcellos, Lisa F; Agliardi, Cristina; Alfredsson, Lars; Alizadeh, Mehdi; Anderson, Carl; Andrews, Robert; Søndergaard, Helle Bach; Baker, Amie; Band, Gavin; Baranzini, Sergio E; Barizzone, Nadia; Barrett, Jeffrey; Bellenguez, Céline; Bergamaschi, Laura; Bernardinelli, Luisa; Berthele, Achim; Biberacher, Viola; Binder, Thomas M C; Blackburn, Hannah; Bomfim, Izaura L; Brambilla, Paola; Broadley, Simon; Brochet, Bruno; Brundin, Lou; Buck, Dorothea; Butzkueven, Helmut; Caillier, Stacy J; Camu, William; Carpentier, Wassila; Cavalla, Paola; Celius, Elisabeth G; Coman, Irène; Comi, Giancarlo; Corrado, Lucia; Cosemans, Leentje; Cournu-Rebeix, Isabelle; Cree, Bruce A C; Cusi, Daniele; Damotte, Vincent; Defer, Gilles; Delgado, Silvia R; Deloukas, Panos; di Sapio, Alessia; Dilthey, Alexander T; Donnelly, Peter; Dubois, Bénédicte; Duddy, Martin; Edkins, Sarah; Elovaara, Irina; Esposito, Federica; Evangelou, Nikos; Fiddes, Barnaby; Field, Judith; Franke, Andre; Freeman, Colin; Frohlich, Irene Y; Galimberti, Daniela; Gieger, Christian; Gourraud, Pierre-Antoine; Graetz, Christiane; Graham, Andrew; Grummel, Verena; Guaschino, Clara; Hadjixenofontos, Athena; Hakonarson, Hakon; Halfpenny, Christopher; Hall, Gillian; Hall, Per; Hamsten, Anders; Harley, James; Harrower, Timothy; Hawkins, Clive; Hellenthal, Garrett; Hillier, Charles; Hobart, Jeremy; Hoshi, Muni; Hunt, Sarah E; Jagodic, Maja; Jelčić, Ilijas; Jochim, Angela; Kendall, Brian; Kermode, Allan; Kilpatrick, Trevor; Koivisto, Keijo; Konidari, Ioanna; Korn, Thomas; Kronsbein, Helena; Langford, Cordelia; Larsson, Malin; Lathrop, Mark; Lebrun-Frenay, Christine; Lechner-Scott, Jeannette; Lee, Michelle H; Leone, Maurizio A; Leppä, Virpi; Liberatore, Giuseppe; Lie, Benedicte A; Lill, Christina M; Lindén, Magdalena; Link, Jenny; Luessi, Felix; Lycke, Jan; Macciardi, Fabio; Männistö, Satu; Manrique, Clara P; Martin, Roland; Martinelli, Vittorio; Mason, Deborah; Mazibrada, Gordon; McCabe, Cristin; Mero, Inger-Lise; Mescheriakova, Julia; Moutsianas, Loukas; Myhr, Kjell-Morten; Nagels, Guy; Nicholas, Richard; Nilsson, Petra; Piehl, Fredrik; Pirinen, Matti; Price, Siân E; Quach, Hong; Reunanen, Mauri; Robberecht, Wim; Robertson, Neil P; Rodegher, Mariaemma; Rog, David; Salvetti, Marco; Schnetz-Boutaud, Nathalie C; Sellebjerg, Finn; Selter, Rebecca C; Schaefer, Catherine; Shaunak, Sandip; Shen, Ling; Shields, Simon; Siffrin, Volker; Slee, Mark; Sorensen, Per Soelberg; Sorosina, Melissa; Sospedra, Mireia; Spurkland, Anne; Strange, Amy; Sundqvist, Emilie; Thijs, Vincent; Thorpe, John; Ticca, Anna; Tienari, Pentti; van Duijn, Cornelia; Visser, Elizabeth M; Vucic, Steve; Westerlind, Helga; Wiley, James S; Wilkins, Alastair; Wilson, James F; Winkelmann, Juliane; Zajicek, John; Zindler, Eva; Haines, Jonathan L; Pericak-Vance, Margaret A; Ivinson, Adrian J; Stewart, Graeme; Hafler, David; Hauser, Stephen L; Compston, Alastair; McVean, Gil; De Jager, Philip; Sawcer, Stephen; McCauley, Jacob L

2013-01-01

Using the ImmunoChip custom genotyping array, we analysed 14,498 multiple sclerosis subjects and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (p-value < 1.0 × 10-4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 multiple sclerosis subjects and 26,703 healthy controls. In these 80,094 individuals of European ancestry we identified 48 new susceptibility variants (p-value < 5.0 × 10-8); three found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants in 103 discrete loci outside of the Major Histocompatibility Complex. With high resolution Bayesian fine-mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalogue of multiple sclerosis risk variants and illustrates the value of fine-mapping in the resolution of GWAS signals. PMID:24076602

Treatment of progressive multiple sclerosis: what works, what does not, and what is needed.

PubMed

Feinstein, Anthony; Freeman, Jenny; Lo, Albert C

2015-02-01

Disease-modifying drugs have mostly failed as treatments for progressive multiple sclerosis. Management of the disease therefore solely aims to minimise symptoms and, if possible, improve function. The degree to which this approach is based on empirical data derived from studies of progressive disease or whether treatment decisions are based on what is known about relapsing-remitting disease remains unclear. Symptoms rated as important by patients with multiple sclerosis include balance and mobility impairments, weakness, reduced cardiovascular fitness, ataxia, fatigue, bladder dysfunction, spasticity, pain, cognitive deficits, depression, and pseudobulbar affect; a comprehensive literature search shows a notable paucity of studies devoted solely to these symptoms in progressive multiple sclerosis, which translates to few proven therapeutic options in the clinic. A new strategy that can be used in future rehabilitation trials is therefore needed, with the adoption of approaches that look beyond single interventions to concurrent, potentially synergistic, treatments that maximise what remains of neural plasticity in patients with progressive multiple sclerosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

A passive exoskeleton can push your life up: application on multiple sclerosis patients.

PubMed

Di Russo, Francesco; Berchicci, Marika; Perri, Rinaldo Livio; Ripani, Francesca Romana; Ripani, Maurizio

2013-01-01

In the present study, we report the benefits of a passive and fully articulated exoskeleton on multiple sclerosis patients by means of behavioral and electrophysiological measures, paying particular attention to the prefrontal cortex activity. Multiple sclerosis is a neurological condition characterized by lesions of the myelin sheaths that encapsulate the neurons of the brain, spine and optic nerve, and it causes transient or progressive symptoms and impairments in gait and posture. Up to 50% of multiple sclerosis patients require walking aids and 10% are wheelchair-bound 15 years following the initial diagnosis. We tested the ability of a new orthosis, the "Human Body Posturizer", designed to improve the structural and functional symmetry of the body through proprioception, in multiple sclerosis patients. We observed that a single Human Body Posturizer application improved mobility, ambulation and response accuracy, in all of the tested patients. Most importantly, we associated these clinical observations and behavioral effects to changes in brain activity, particularly in the prefrontal cortex.

The Validity and Test-Retest Reliability of the Leeds Multiple Sclerosis Quality of Life Scale in Turkish Patients

ERIC Educational Resources Information Center

Akbiyik, Derya Iren; Sumbuloglu, Vildan; Guney, Zafer; Armutlu, Kadriye; Korkmaz, Nilufer; Keser, Ilke; Yuksel, Muazzez Merve; Karabudak, Rana

2009-01-01

The aim of the study was to translate and test the reliability and validity of the Leeds Multiple Sclerosis Quality of Life Scale (LMSQoL) in Turkish patients with multiple sclerosis (MS). Demographic data of MS patients who had a registration in and followed up by a university hospital were recorded. The LMSQoL and Turkish Quality of Life…

The Effects of Gain- versus Loss-Framed Messages Following Health Risk Information on Physical Activity in Individuals With Multiple Sclerosis.

PubMed

Lithopoulos, Alexander; Bassett-Gunter, Rebecca L; Martin Ginis, Kathleen A; Latimer-Cheung, Amy E

2017-06-01

Few people with multiple sclerosis engage in physical activity. Messaging interventions may motivate more physical activity among these individuals. The purpose of this online study was to evaluate an intervention presenting participants with multiple sclerosis (N = 237) with risk information (i.e., information demonstrating people with multiple sclerosis are more likely to experience certain health issues) or no risk information followed by gain- or loss-framed physical activity messages. Participants completed questionnaires on Days 1, 6, and 28 and received information material on Days 2-5. The dependent variables were as follows: physical activity intentions and behavior, response and task efficacy, perceived threat (i.e., perception of threat to health issues relevant to people with multiple sclerosis), and avoidance (i.e., avoiding thinking about/doing something about the health issues presented in the messages). Analyses indicated physical activity and response efficacy increased over time. Also, participants receiving risk information had higher levels of physical activity and perceived threat. However, manipulation checks showed no differences between participants regarding perceptions of risk information or gain/loss-framed messages. Despite the lack of impact of the framing intervention, this study suggests that a brief informational intervention can positively influence physical activity and certain correlates of physical activity among people with multiple sclerosis.

Fingolimod hydrochloride for the treatment of relapsing remitting multiple sclerosis.

PubMed

Thomas, Katja; Proschmann, Undine; Ziemssen, Tjalf

2017-10-01

Fingolimod was the first oral and the first in class disease modifying treatment in multiple sclerosis that acts as sphingosine-1-phospathe receptor agonist. Since approval in 2010 there is a growing experience with fingolimod use in clinical practice, but also next-generation sphingosin-1-receptor agonists in ongoing clinical trials. Growing evidence demonstrates additional effects beyond impact on lymphocyte circulation, highlighting further promising targets in multiple sclerosis therapy. Areas covered: Here we present a systematic review using PubMed database searching and expert opinion on fingolimod use in clinical practice. Long-term data of initial clinical trials and post-marketing evaluations including long-term efficacy, safety, tolerability and management especially within growing disease modifying treatment options and pre-treatment constellation in multiple sclerosis patients are critically discussed. Furthermore novel findings in mechanism of actions and prospective on additional use in progressive forms in multiple sclerosis are presented. Expert opinion: There is an extensive long-term experience on fingolimod use in clinical practice demonstrating the favorable benefit-risk of this drug. Using a defined risk management approach experienced MS clinicians should apply fingolimod after critical choice of patients and review of clinical aspects. Further studies are essential to discuss additional benefit in progressive forms in multiple sclerosis.

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

PubMed

Khalili, Mohammad; Eghtesadi, Shahryar; Mirshafiey, Abbas; Eskandari, Ghazaleh; Sanoobar, Meisam; Sahraian, Mohamad Ali; Motevalian, Abbas; Norouzi, Abbas; Moftakhar, Shirin; Azimi, Amirreza

2014-01-01

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. 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. 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. 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.

Physician compensation for industry-sponsored clinical trials in multiple sclerosis influences patient trust.

PubMed

Klein, E; Solomon, A J; Corboy, J; Bernat, J

2016-07-01

Perceived physician financial conflicts of interest of can affect patient trust. Payment to physicians for industry sponsored clinical trials in multiple sclerosis is a relatively new potential source of physician conflict of interest. There is limited available data on how physician payment for trial involvement in multiple sclerosis clinical trials may influence patient trust. To understand how patient trust is influenced by information about physician payment for multiple sclerosis clinical trials. An anonymous online instrument was developed. 597 people with multiple sclerosis participated in the study. The study found that 61% of patients who had not previously participated in a clinical trial estimated that they would have lower levels of trust in their physician if the physician was paid for involvement in their clinical trial. Among former clinical trial participants, 38% self-reported a lower level of trust. Other potential physician-industry relationships, such as industry consulting or giving industry-sponsored talks, also adversely affected trust, though to a lesser extent than physician payment for subject participation in clinical trials. Results of this study demonstrate that physician payment for study participation in multiple sclerosis clinical trials is a potential conflict that can adversely affect patient trust. Copyright © 2016 Elsevier B.V. All rights reserved.

Lateral interactions and speed of information processing in highly functioning multiple sclerosis patients.

PubMed

Nagy, Helga; Bencsik, Krisztina; Rajda, Cecília; Benedek, Krisztina; Janáky, Márta; Beniczky, Sándor; Kéri, Szabolcs; Vécsei, László

2007-06-01

Visual impairment is a common feature of multiple sclerosis. The aim of this study was to investigate lateral interactions in the visual cortex of highly functioning patients with multiple sclerosis and to compare that with basic visual and neuropsychologic functions. Twenty-two young, visually unimpaired multiple sclerosis patients with minimal symptoms (Expanded Disability Status Scale <2) and 30 healthy controls subjects participated in the study. Lateral interactions were investigated with the flanker task, during which participants were asked to detect the orientation of a low-contrast Gabor patch (vertical or horizontal), flanked with 2 collinear or orthogonal Gabor patches. Stimulus exposure time was 40, 60, 80, and 100 ms. Digit span forward/backward, digit symbol, verbal fluency, and California Verbal Learning Test procedures were used for background neuropsychologic assessment. Results revealed that patients with multiple sclerosis showed intact visual contrast sensitivity and neuropsychologic functions, whereas orientation detection in the orthogonal condition was significantly impaired. At 40-ms exposure time, collinear flankers facilitated the orientation detection performance of the patients resulting in normal performance. In conclusion, the detection of briefly presented, low-contrast visual stimuli was selectively impaired in multiple sclerosis. Lateral interactions between target and flankers robustly facilitated target detection in the patient group.

Incidence of multiple sclerosis among European Economic Area populations, 1985-2009: the framework for monitoring

PubMed Central

2013-01-01

Background A debate surrounding multiple sclerosis epidemiology has centred on time-related incidence increases and the need of monitoring. The purpose of this study is to reassess multiple sclerosis incidence in the European Economic Area. Methods We conducted a systematic review of literature from 1965 onwards and integrated elements of original research, including requested or completed data by surveys authors and specific analyses. Results The review of 5323 documents yielded ten studies for age- and sex-specific analyses, and 21 studies for time-trend analysis of single data sets. After 1985, the incidence of multiple sclerosis ranged from 1.12 to 6.96 per 100,000 population, was higher in females, tripled with latitude, and doubled with study midpoint year. The north registered increasing trends from the 1960s and 1970s, with a historic drop in the Faroe Islands, and fairly stable data in the period 1980-2000; incidence rose in Italian and French populations in the period 1970-2000, in Evros (Greece) in the 1980s, and in the French West Indies in around 2000. Conclusions We conclude that the increase in multiple sclerosis incidence is only apparent, and that it is not specific to women. Monitoring of multiple sclerosis incidence might be appropriate for the European Economic Area. PMID:23758972

Effect of integrated Yoga and Physical therapy on audiovisual reaction time, anxiety and depression in patients with chronic multiple sclerosis: a pilot study.

PubMed

Chobe, Shivaji; Bhargav, Hemant; Raghuram, Nagarathna; Garner, Christoph

2016-09-01

Multiple sclerosis (MS) is characterized by a significant deterioration in auditory and visual reaction times along with associated depression and anxiety. Yoga and Physical therapy (PT) interventions have been found to enhance recovery from these problems in various neuropsychiatric illnesses, but sufficient evidence is lacking in chronic MS population. The aim of this study was to assess the effect of integrated Yoga and Physical therapy (IYP) on audiovisual reaction times, depression and anxiety in patients suffering from chronic MS. From a neuro-rehabilitation center in Germany, 11 patients (six females) suffering from MS for 19±7.4 years were recruited. Subjects were in the age range of 55.45±10.02 years and had Extended Disability Status Scores (EDSS) below 7. All the subjects received mind-body intervention of integrated Yoga and Physical therapy (IYP) for 3 weeks. The intervention was given in a residential setup. Patients followed a routine involving Yogic physical postures, pranayama, and meditations along with various Physical therapy (PT) techniques for 21 days, 5 days a week, 5 h/day. They were assessed before and after intervention for changes in audiovisual reaction times (using Brain Fit Model No. OT 400), anxiety, and depression [using Hospital Anxiety and Depression Scale (HADS)]. Data was analyzed using paired samples test. There was significant improvement in visual reaction time (p=0.01), depression (p=0.04), and anxiety (p=0.02) scores at the end of 3 weeks as compared to the baseline. Auditory reaction time showed reduction with borderline statistical significance (p=0.058). This pilot project suggests utility of IYP intervention for improving audiovisual reaction times and psychological health in chronic MS patients. In future, randomized controlled trials with larger sample size should be performed to confirm these findings.

Online Depressive Symptom Self-Management: Comparing Program Outcomes for Adults With Multiple Sclerosis Versus Those With Other Chronic Diseases.

PubMed

Tietjen, Kiira; Wilson, Marian; Amiri, Solmaz; Dietz, Jeremy

2018-02-01

The goals of the study were to evaluate participant engagement and effects of an Internet-based, self-directed program for depressive symptoms. We compared outcomes of adults with multiple sclerosis (MS) with those of adults with other chronic diseases. This was a secondary analysis of a randomized controlled pilot study. Data were explored for differences between people diagnosed with MS and those with other chronic disease diagnoses. Data were obtained from 47 participants who participated in the original parent study (11 had MS). Participants with at least a moderate preexisting depressive symptom burden on the Patient Health Questionnaire (PHQ) were randomly divided into either a control group or the 8-week "Think Clearly About Depression" online depression self-management program. Study tools were administered at baseline, week 4, and week 8 to evaluate whether the online program improved depressive symptom self-management. Analysis examined differences between participants with and without an MS diagnosis in the treatment and control groups. Average baseline depressive symptom burdens were severe for those with MS and those without MS as measured by the PHQ. Number needed to treat analysis indicated that 1 in every 2 treatment group participants with MS found clinically significant reductions in depressive symptoms by week 8. All participants with MS completed all online program modules. When compared with those with other chronic diseases, participants with MS showed a trend toward greater improvements in the PHQ and health distress scores in addition to self-efficacy in exercising regularly, social/recreational activities, and controlling/managing depression at the end of 8 weeks. An online depressive symptom self-management program is acceptable to people with MS and may be helpful to address undertreated depressive symptoms. The number of participants limits available statistics and ability to generalize results.

Internet-based home training is capable to improve balance in multiple sclerosis: a randomized controlled trial.

PubMed

Frevel, D; Mäurer, M

2015-02-01

Balance disorders are common in multiple sclerosis. Aim of the study is to investigate the effectiveness of an Internet-based home training program (e-Training) to improve balance in patients with multiple sclerosis. A randomized, controlled study. Academic teaching hospital in cooperation with the therapeutic riding center Gut Üttingshof, Bad Mergentheim. Eighteen multiple sclerosis patients (mean EDSS 3,5) took part in the trial. Outcome of patients using e-Training (N.=9) was compared to the outcome of patients receiving hippotherapy (N.=9), which can be considered as an advanced concept for the improvement of balance and postural control in multiple sclerosis. After simple random allocation patients received hippotherapy or Internet-based home training (balance, postural control and strength training) twice a week for 12 weeks. Assessments were done before and after the intervention and included static and dynamic balance (primary outcome). Isometric muscle strength of the knee and trunk extension/flexion (dynamometer), walking capacity, fatigue and quality of life served as secondary outcome parameters. Both intervention groups showed comparable and highly significant improvement in static and dynamic balance capacity, no difference was seen between the both intervention groups. However looking at fatigue and quality of life only the group receiving hippotherapy improved significantly. Since e-Training shows even comparable effects to hippotherapy to improve balance, we believe that the established Internet-based home training program, specialized on balance and postural control training, is feasible for a balance and strength training in persons with multiple sclerosis. We demonstrated that Internet-based home training is possible in patients with multiple sclerosis.

The Emerging Role of Zinc in the Pathogenesis of Multiple Sclerosis.

PubMed

Choi, Bo Young; Jung, Jong Won; Suh, Sang Won

2017-09-28

Our lab has previously demonstrated that multiple sclerosis-induced spinal cord white matter damage and motor deficits are mediated by the pathological disruption of zinc homeostasis. Abnormal vesicular zinc release and intracellular zinc accumulation may mediate several steps in the pathophysiological processes of multiple sclerosis (MS), such as matrix metallopeptidase 9 (MMP-9) activation, blood-brain barrier (BBB) disruption, and subsequent immune cell infiltration from peripheral systems. Oral administration of a zinc chelator decreased BBB disruption, immune cell infiltration, and spinal white matter myelin destruction. Therefore, we hypothesized that zinc released into the extracellular space during MS progression is involved in destruction of the myelin sheath in spinal cord white mater and in generation of motor deficits. To confirm our previous study, we employed zinc transporter 3 ( ZnT3 ) knockout mice to test whether vesicular zinc depletion shows protective effects on multiple sclerosis-induced white matter damage and motor deficits. ZnT3 gene deletion profoundly reduced the daily clinical score of experimental autoimmune encephalomyelitis (EAE) by suppression of inflammation and demyelination in the spinal cord. ZnT3 gene deletion also remarkably inhibited formation of multiple sclerosis-associated aberrant synaptic zinc patches, MMP-9 activation, and BBB disruption. These two studies strongly support our hypothesis that zinc release from presynaptic terminals may be involved in multiple sclerosis pathogenesis. Further studies will no doubt continue to add mechanistic detail to this process and with luck, clarify how these observations may lead to development of novel therapeutic approaches for the treatment of multiple sclerosis.

Delayed P100-Like Latencies in Multiple Sclerosis: A Preliminary Investigation Using Visual Evoked Spread Spectrum Analysis

PubMed Central

Kiiski, Hanni S. M.; Ní Riada, Sinéad; Lalor, Edmund C.; Gonçalves, Nuno R.; Nolan, Hugh; Whelan, Robert; Lonergan, Róisín; Kelly, Siobhán; O'Brien, Marie Claire; Kinsella, Katie; Bramham, Jessica; Burke, Teresa; Ó Donnchadha, Seán; Hutchinson, Michael; Tubridy, Niall; Reilly, Richard B.

2016-01-01

Conduction along the optic nerve is often slowed in multiple sclerosis (MS). This is typically assessed by measuring the latency of the P100 component of the Visual Evoked Potential (VEP) using electroencephalography. The Visual Evoked Spread Spectrum Analysis (VESPA) method, which involves modulating the contrast of a continuous visual stimulus over time, can produce a visually evoked response analogous to the P100 but with a higher signal-to-noise ratio and potentially higher sensitivity to individual differences in comparison to the VEP. The main objective of the study was to conduct a preliminary investigation into the utility of the VESPA method for probing and monitoring visual dysfunction in multiple sclerosis. The latencies and amplitudes of the P100-like VESPA component were compared between healthy controls and multiple sclerosis patients, and multiple sclerosis subgroups. The P100-like VESPA component activations were examined at baseline and over a 3-year period. The study included 43 multiple sclerosis patients (23 relapsing-remitting MS, 20 secondary-progressive MS) and 42 healthy controls who completed the VESPA at baseline. The follow-up sessions were conducted 12 months after baseline with 24 MS patients (15 relapsing-remitting MS, 9 secondary-progressive MS) and 23 controls, and again at 24 months post-baseline with 19 MS patients (13 relapsing-remitting MS, 6 secondary-progressive MS) and 14 controls. The results showed P100-like VESPA latencies to be delayed in multiple sclerosis compared to healthy controls over the 24-month period. Secondary-progressive MS patients had most pronounced delay in P100-like VESPA latency relative to relapsing-remitting MS and controls. There were no longitudinal P100-like VESPA response differences. These findings suggest that the VESPA method is a reproducible electrophysiological method that may have potential utility in the assessment of visual dysfunction in multiple sclerosis. PMID:26726800

A discrete-choice experiment to determine patient preferences for injectable multiple sclerosis treatments in Germany.

PubMed

Poulos, Christine; Kinter, Elizabeth; Yang, Jui-Chen; Bridges, John F P; Posner, Joshua; Gleißner, Erika; Mühlbacher, Axel; Kieseier, Bernd

2016-03-01

The aim of this study was to assess the relative importance of features of a hypothetical injectable disease-modifying treatment for patients with multiple sclerosis using a discrete-choice experiment. German residents at least 18 years of age with a self-reported physician diagnosis of multiple sclerosis completed a 25-30 minute online discrete-choice experiment. Patients were asked to choose one of two hypothetical injectable treatments for multiple sclerosis, defined by different levels of six attributes (disability progression, the number of relapses in the next 4 years, injection time, frequency of injections, presence of flu-like symptoms, and presence of injection-site reactions). The data were analyzed using a random-parameters logit model. Of 202 adults who completed the survey, results from 189 were used in the analysis. Approximately 50% of all patients reported a diagnosis of relapsing-remitting multiple sclerosis, and 31% reported secondary progressive multiple sclerosis. Approximately 71% of patients had current or prior experience with injectable multiple sclerosis medication. Approximately 53% had experienced flu-like symptoms caused by their medication, and 47% had experienced mild injection-site reactions. At least one significant difference was seen between levels in all attributes, except injection time. The greatest change in relative importance between levels of an attribute was years until symptoms get worse from 1 to 4 years. The magnitude of this difference was about twice that of relapses in the next 4 years, frequency of injections, and flu-like symptoms. Most attributes examined in this experiment had an influence on patient preference. Patients placed a significant value on improvements in the frequency of dosing and disability progression. Results suggest that changes in injection frequency can be as important as changes in efficacy and safety attributes. Understanding which attributes of injectable therapies influence patient preference could potentially improve outcomes and adherence in patients with multiple sclerosis.

T helper 17.1 cells associate with multiple sclerosis disease activity: perspectives for early intervention.

PubMed

van Langelaar, Jamie; van der Vuurst de Vries, Roos M; Janssen, Malou; Wierenga-Wolf, Annet F; Spilt, Isis M; Siepman, Theodora A; Dankers, Wendy; Verjans, Georges M G M; de Vries, Helga E; Lubberts, Erik; Hintzen, Rogier Q; van Luijn, Marvin M

2018-05-01

Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as critical regulators of multiple sclerosis disease activity. However, depending on the species and pro-inflammatory milieu, Th17 cells are functionally heterogeneous, consisting of subpopulations that differentially produce interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating factor. In the current study, we studied distinct effector phenotypes of human Th17 cells and their correlation with disease activity in multiple sclerosis patients. T helper memory populations single- and double-positive for C-C chemokine receptor 6 (CCR6) and CXC chemokine receptor 3 (CXCR3) were functionally assessed in blood and/or cerebrospinal fluid from a total of 59 patients with clinically isolated syndrome, 35 untreated patients and 24 natalizumab-treated patients with relapsing-remitting multiple sclerosis, and nine patients with end-stage multiple sclerosis. Within the clinically isolated syndrome group, 23 patients had a second attack within 1 year and 26 patients did not experience subsequent attacks during a follow-up of >5 years. Low frequencies of T helper 1 (Th1)-like Th17 (CCR6+CXCR3+), and not Th17 (CCR6+CXCR3-) effector memory populations in blood strongly associated with a rapid diagnosis of clinically definite multiple sclerosis. In cerebrospinal fluid of clinically isolated syndrome and relapsing-remitting multiple sclerosis patients, Th1-like Th17 effector memory cells were abundant and showed increased production of interferon-gamma and granulocyte macrophage colony-stimulating factor compared to paired CCR6+ and CCR6-CD8+ T cell populations and their blood equivalents after short-term culturing. Their local enrichment was confirmed ex vivo using cerebrospinal fluid and brain single-cell suspensions. Across all pro-inflammatory T helper cells analysed in relapsing-remitting multiple sclerosis blood, Th1-like Th17 subpopulation T helper 17.1 (Th17.1; CCR6+CXCR3+CCR4-) expressed the highest very late antigen-4 levels and selectively accumulated in natalizumab-treated patients who remained free of clinical relapses. This was not found in patients who experienced relapses during natalizumab treatment. The enhanced potential of Th17.1 cells to infiltrate the central nervous system was supported by their predominance in cerebrospinal fluid of early multiple sclerosis patients and their preferential transmigration across human brain endothelial layers. These findings reveal a dominant contribution of Th1-like Th17 subpopulations, in particular Th17.1 cells, to clinical disease activity and provide a strong rationale for more specific and earlier use of T cell-targeted therapy in multiple sclerosis.

Trial of Minocycline in a Clinically Isolated Syndrome of Multiple Sclerosis.

PubMed

Metz, Luanne M; Li, David K B; Traboulsee, Anthony L; Duquette, Pierre; Eliasziw, Misha; Cerchiaro, Graziela; Greenfield, Jamie; Riddehough, Andrew; Yeung, Michael; Kremenchutzky, Marcelo; Vorobeychik, Galina; Freedman, Mark S; Bhan, Virender; Blevins, Gregg; Marriott, James J; Grand'Maison, Francois; Lee, Liesly; Thibault, Manon; Hill, Michael D; Yong, V Wee

2017-06-01

On the basis of encouraging preliminary results, we conducted a randomized, controlled trial to determine whether minocycline reduces the risk of conversion from a first demyelinating event (also known as a clinically isolated syndrome) to multiple sclerosis. During the period from January 2009 through July 2013, we randomly assigned participants who had had their first demyelinating symptoms within the previous 180 days to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of multiple sclerosis was established or until 24 months after randomization, whichever came first. The primary outcome was conversion to multiple sclerosis (diagnosed on the basis of the 2005 McDonald criteria) within 6 months after randomization. Secondary outcomes included conversion to multiple sclerosis within 24 months after randomization and changes on magnetic resonance imaging (MRI) at 6 months and 24 months (change in lesion volume on T 2 -weighted MRI, cumulative number of new lesions enhanced on T 1 -weighted MRI ["enhancing lesions"], and cumulative combined number of unique lesions [new enhancing lesions on T 1 -weighted MRI plus new and newly enlarged lesions on T 2 -weighted MRI]). A total of 142 eligible participants underwent randomization at 12 Canadian multiple sclerosis clinics; 72 participants were assigned to the minocycline group and 70 to the placebo group. The mean age of the participants was 35.8 years, and 68.3% were women. The unadjusted risk of conversion to multiple sclerosis within 6 months after randomization was 61.0% in the placebo group and 33.4% in the minocycline group, a difference of 27.6 percentage points (95% confidence interval [CI], 11.4 to 43.9; P=0.001). After adjustment for the number of enhancing lesions at baseline, the difference in the risk of conversion to multiple sclerosis within 6 months after randomization was 18.5 percentage points (95% CI, 3.7 to 33.3; P=0.01); the unadjusted risk difference was not significant at the 24-month secondary outcome time point (P=0.06). All secondary MRI outcomes favored minocycline over placebo at 6 months but not at 24 months. Trial withdrawals and adverse events of rash, dizziness, and dental discoloration were more frequent among participants who received minocycline than among those who received placebo. The risk of conversion from a clinically isolated syndrome to multiple sclerosis was significantly lower with minocycline than with placebo over 6 months but not over 24 months. (Funded by the Multiple Sclerosis Society of Canada; ClinicalTrials.gov number, NCT00666887 .).

Calcium channel blockers and esophageal sclerosis: should we expect exacerbation of interstitial lung disease?

PubMed

Seretis, Charalampos; Seretis, Fotios; Gemenetzis, George; Liakos, Nikolaos; Pappas, Apostolos; Gourgiotis, Stavros; Lagoudianakis, Emmanuel; Keramidaris, Dimitrios; Salemis, Nikolaos

2012-01-01

Esophageal sclerosis is the most common visceral manifestation of systemic sclerosis, resulting in impaired esophageal clearance and retention of ingested food; in addition, co-existence of lung fibrosis with esophageal scleroderma is not uncommon. Both the progression of generalized connective tissue disorders and the damaging effect of chronic aspiration due to esophageal dysmotility appear to be involved in this procedure of interstitial fibrosis. Nifedipine is a widely prescribed calcium antagonist in a significant percentage of rheumatologic patients suffering from Raynaud syndrome, in order to inhibit peripheral vasospasm. Nevertheless, blocking calcium channels has proven to contribute to exacerbation of gastroesophageal reflux, which consequently can lead to chronic aspiration. We describe the case of severe exacerbation of interstitial lung disease in a 76-year-old female with esophageal sclerosis who was treated with oral nifedipine for Raynaud syndrome.

What Is Leukodystrophy

MedlinePlus

... having the disease. Are the leukodystrophies related to Multiple Sclerosis? The leukodystrophies do share some common features with multiple sclerosis (MS). Like the leukodystrophies, MS is caused by ...

Creatine Enhances Mitochondrial-Mediated Oligodendrocyte Survival After Demyelinating Injury

PubMed Central

Nanescu, Sonia E.

2017-01-01

Chronic oligodendrocyte loss, which occurs in the demyelinating disorder multiple sclerosis (MS), contributes to axonal dysfunction and neurodegeneration. Current therapies are able to reduce MS severity, but do not prevent transition into the progressive phase of the disease, which is characterized by chronic neurodegeneration. Therefore, pharmacological compounds that promote oligodendrocyte survival could be beneficial for neuroprotection in MS. Here, we investigated the role of creatine, an organic acid involved in adenosine triphosphate (ATP) buffering, in oligodendrocyte function. We found that creatine increased mitochondrial ATP production directly in oligodendrocyte lineage cell cultures and exerted robust protection on oligodendrocytes by preventing cell death in both naive and lipopolysaccharide-treated mixed glia. Moreover, lysolecithin-mediated demyelination in mice deficient in the creatine-synthesizing enzyme guanidinoacetate-methyltransferase (Gamt) did not affect oligodendrocyte precursor cell recruitment, but resulted in exacerbated apoptosis of regenerated oligodendrocytes in central nervous system (CNS) lesions. Remarkably, creatine administration into Gamt-deficient and wild-type mice with demyelinating injury reduced oligodendrocyte apoptosis, thereby increasing oligodendrocyte density and myelin basic protein staining in CNS lesions. We found that creatine did not affect the recruitment of macrophages/microglia into lesions, suggesting that creatine affects oligodendrocyte survival independently of inflammation. Together, our results demonstrate a novel function for creatine in promoting oligodendrocyte viability during CNS remyelination. SIGNIFICANCE STATEMENT We report that creatine enhances oligodendrocyte mitochondrial function and protects against caspase-dependent oligodendrocyte apoptosis during CNS remyelination. This work has important implications for the development of therapeutic targets for diseases characterized by oligodendrocyte death, including multiple sclerosis. PMID:28069926

Social Media Representation of Chronic Cerebrospinal Venous Insufficiency Intervention for Multiple Sclerosis

PubMed Central

Forwell, Susan J.

2016-01-01

Background: We conducted a rigorous review of videos related to multiple sclerosis (MS) and chronic cerebrospinal venous insufficiency (CCSVI) treatment posted by people with MS on one social media website (YouTube) that describe symptoms before and after the surgical procedure, as well as videos presented by health-care professionals (HCPs). Methods: All relevant videos posted from December 2009 to July 2011 were downloaded, viewed, and systematically organized. Categorical data were classified, and dominant messages were gleaned. Results: A total of 1789 videos were extracted. A total of 621 videos by people with MS and 238 by HCPs were included. Eighty-six percent of people with MS anecdotally reported experiencing some improvement in at least one symptom. The most common message was that “CCSVI is not a miracle but worth trying.” Most HCPs posting videos recommended the procedure but called for continued research. Conclusions: Social media are conveying an anecdotal favorable message about CCSVI treatment for MS. The relative absence of videos offering a negative or more balanced perspective is a concern. Social persuasion through these videos creates a strong positive impression of CCSVI treatment, but the videos do not acknowledge the lack of supporting scientific evidence and the possible role of the placebo effect. Given the strong influence of social media on health-care decision making, researchers and clinicians should actively use social media to reach out to people with MS and describe the state of the evidence for MS treatments, both positive and negative. PMID:27134577

Directional diffusivity as a magnetic resonance (MR) biomarker in demyelinating disease

NASA Astrophysics Data System (ADS)

Benzinger, Tammie L. S.; Cross, Anne H.; Xu, Junqian; Naismith, Robert; Sun, Shu-Wei; Song, Sheng-Kwei

2007-09-01

Directional diffusivities derived from diffusion tensor magnetic resonance imaging (DTI) measurements describe water movement parallel to (λ ||, axial diffusivity) and perpendicular to (λ⊥radial diffusivity) axonal tracts. λ || and λ⊥ have been shown to differentially detect axon and myelin abnormalities in several mouse models of central nervous system white matter pathology in our laboratory. These models include experimental autoimmune encephalomyelitis (EAE), (1) myelin basic protein mutant mice with dysmyelination and intact axons, (2) cuprizone-induced demyelination, and remyelination, with reversible axon injury (2, 3) and a model of retinal ischemia in which retinal ganglion cell death is followed by Wallerian degeneration of optic nerve, with axonal injury preceding demyelination. (4) Decreased λ|| correlates with acute axonal injury and increased λ⊥ indicates myelin damage. (4) More recently, we have translated this approach to human MR, investigating acute and chronic optic neuritis in adults with multiple sclerosis, brain lesions in adults with multiple sclerosis, and acute disseminated encephalomyelitis (ADEM) in children. We are also investigating the use of this technique to probe the underlying structural change of the cervical spinal cord in acute and chronic T2- hyperintense lesions in spinal stenosis, trauma, and transverse myelitis. In each of these demyelinating diseases, the discrimination between axonal and myelin injury which we can achieve has important prognostic and therapeutic implications. For those patients with myelin injury but intact axons, early, directed drug therapy has the potential to prevent progression to axonal loss and permanent disability.

Treatment strategies for multiple sclerosis: When to start, when to change, when to stop?

PubMed Central

Gajofatto, Alberto; Benedetti, Maria Donata

2015-01-01

Multiple sclerosis (MS) is a chronic inflammatory condition of the central nervous system determined by a presumed autoimmune process mainly directed against myelin components but also involving axons and neurons. Acute demyelination shows as clinical relapses that may fully or partially resolve, while chronic demyelination and neuroaxonal injury lead to persistent and irreversible neurological symptoms, often progressing over time. Currently approved disease-modifying therapies are immunomodulatory or immunosuppressive drugs that significantly although variably reduce the frequency of attacks of the relapsing forms of the disease. However, they have limited efficacy in preventing the transition to the progressive phase of MS and are of no benefit after it has started. It is therefore likely that the potential advantage of a given treatment is condensed in a relatively limited window of opportunity for each patient, depending on individual characteristics and disease stage, most frequently but not necessarily in the early phase of the disease. In addition, a sizable proportion of patients with MS may have a very mild clinical course not requiring a disease-modifying therapy. Finally, individual response to existing therapies for MS varies significantly across subjects and the risk of serious adverse events remains an issue, particularly for the newest agents. The present review is aimed at critically describing current treatment strategies for MS with a particular focus on the decision of starting, switching and stopping commercially available immunomodulatory and immunosuppressive therapies. PMID:26244148

Exercise and multiple sclerosis.

PubMed

White, Lesley J; Dressendorfer, Rudolph H

2004-01-01

The pathophysiology of multiple sclerosis (MS) is characterised by fatigue, motor weakness, spasticity, poor balance, heat sensitivity and mental depression. Also, MS symptoms may lead to physical inactivity associated with the development of secondary diseases. Persons with MS are thus challenged by their disability when attempting to pursue an active lifestyle compatible with health-related fitness. Although exercise prescription is gaining favour as a therapeutic strategy to minimise the loss of functional capacity in chronic diseases, it remains under-utilised as an intervention strategy in the MS population. However, a growing number of studies indicate that exercise in patients with mild-to-moderate MS provides similar fitness and psychological benefits as it does in healthy controls. We reviewed numerous studies describing the responses of selected MS patients to acute and chronic exercise compared with healthy controls. All training studies reported positive outcomes that outweighed potential adverse effects of the exercise intervention. Based on our review, this article highlights the role of exercise prescription in the multidisciplinary approach to MS disease management for improving and maintaining functional capacity. Despite the often unpredictable clinical course of MS, exercise programmes designed to increase cardiorespiratory fitness, muscle strength and mobility provide benefits that enhance lifestyle activity and quality of life while reducing risk of secondary disorders. Recommendations for the evaluation of cardiorespiratory fitness, muscle performance and flexibility are presented as well as basic guidelines for individualised exercise testing and training in MS. Special considerations for exercise, including medical management concerns, programme modifications and supervision, in the MS population are discussed.

The role of gut microbiome and associated metabolome in the regulation of neuroinflammation in multiple sclerosis and its implications in attenuating chronic inflammation in other inflammatory and autoimmune disorders.

PubMed

Dopkins, Nicholas; Nagarkatti, Prakash S; Nagarkatti, Mitzi

2018-06-01

The importance of the gut microbiome in the regulation of non-infectious diseases has earned unprecedented interest from biomedical researchers. Widespread use of next-generation sequencing techniques has prepared a foundation for further research by correlating the presence of specific bacterial species with the onset or severity of a disease state, heralding paradigm-shifting results. This review covers the mechanisms through which a dysbiotic gut microbiota contributes to the pathological symptoms in an autoimmune neurodegenerative disorder, multiple sclerosis (MS). Although the central nervous system (CNS) is protected by the blood-brain barrier (BBB), it is unclear how gut dysbiosis can trigger potential immunological changes in the CNS in the presence of the BBB. This review focuses on the immunoregulatory functionality of microbial metabolites, which can cross the BBB and mediate their effects directly on immune cells within the CNS and/or indirectly through modulating the response of peripheral T cells to stimulate or inhibit pro-inflammatory chemokines and cytokines, which in turn regulate the autoimmune response in the CNS. Although more research is clearly needed to directly link the changes in gut microbiome with neuroinflammation, focusing research on microbiota that produce beneficial metabolites with the ability to attenuate chronic inflammation systemically as well as in the CNS, can offer novel preventive and therapeutic modalities against a wide array of inflammatory and autoimmune diseases. © 2018 John Wiley & Sons Ltd.

Social Media Representation of Chronic Cerebrospinal Venous Insufficiency Intervention for Multiple Sclerosis.

PubMed

Ghahari, Setareh; Forwell, Susan J

2016-01-01

We conducted a rigorous review of videos related to multiple sclerosis (MS) and chronic cerebrospinal venous insufficiency (CCSVI) treatment posted by people with MS on one social media website (YouTube) that describe symptoms before and after the surgical procedure, as well as videos presented by health-care professionals (HCPs). All relevant videos posted from December 2009 to July 2011 were downloaded, viewed, and systematically organized. Categorical data were classified, and dominant messages were gleaned. A total of 1789 videos were extracted. A total of 621 videos by people with MS and 238 by HCPs were included. Eighty-six percent of people with MS anecdotally reported experiencing some improvement in at least one symptom. The most common message was that "CCSVI is not a miracle but worth trying." Most HCPs posting videos recommended the procedure but called for continued research. Social media are conveying an anecdotal favorable message about CCSVI treatment for MS. The relative absence of videos offering a negative or more balanced perspective is a concern. Social persuasion through these videos creates a strong positive impression of CCSVI treatment, but the videos do not acknowledge the lack of supporting scientific evidence and the possible role of the placebo effect. Given the strong influence of social media on health-care decision making, researchers and clinicians should actively use social media to reach out to people with MS and describe the state of the evidence for MS treatments, both positive and negative.

Disease Modifying Therapy in Multiple Sclerosis

PubMed Central

Williams, U. E.; Oparah, S. K.; Philip-Ephraim, E. E.

2014-01-01

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. PMID:27355035

Design of Chemical Conjugate for Targeted Therapy of Multiple Sclerosis Based of Constant Fragment of Human Antibody Heavy Chain and Peptoid Analog of Autoantigen MOG35-55.

PubMed

Lomakin, Y A; Stepanov, A V; Balabashin, D S; Ponomarenko, N A; Smirnov, I V; Belogurov, A A

2017-04-01

Elimination of B cells producing autoantibodies to neuroantigens is considered as beneficial in the treatment of multiple sclerosis. Myelin oligodendrocyte glycoprotein (MOG) is a significant autoantigen in multiple sclerosis. It was shown that MOG-like peptoid AMogP3 can bind autoantibodies produced by pathological lymphocytes. We propose a structure of an innovative drug for targeted elimination of the pool of autoreactive B cells responsible for multiple sclerosis pathogenesis; this compound is a complex of peptoid AMogP3 with Fc fragment of human immunoglobulin. The obtained Fc-PEG-AMogP3 conjugate effectively interact with autoreactive antibodies, which attests to their high therapeutic potential.

Gestational bisphenol-A exposure lowers the threshold for autoimmunity in a model of multiple sclerosis.

PubMed

Rogers, James A; Mishra, Manoj K; Hahn, Jennifer; Greene, Catherine J; Yates, Robin M; Metz, Luanne M; Yong, V Wee

2017-05-09

Environmental and hormonal factors are implicated in dysimmunity in multiple sclerosis. We investigated whether bisphenol-A, a prominent contaminant with endocrine-disrupting capabilities, altered susceptibility in an inflammatory model of multiple sclerosis. We found that gestational, but not adult, exposure to bisphenol-A increased the development of experimental autoimmune encephalomyelitis in adulthood in male, but not female, mice when a suboptimal disease-inducing immunization was used. Gestational bisphenol-A in male mice primed macrophages in adulthood and raised granulocyte-colony stimulating factor and neutrophil counts/activity postsuboptimal immunization. Neutralizing granulocyte-colony stimulating factor blocked susceptibility to disease in bisphenol-A mice. Early life exposure to bisphenol-A may represent an environmental consideration in multiple sclerosis.

[Immunomodulatory properties of stem mesenchymal cells in autoimmune diseases].

PubMed

Sánchez-Berná, Isabel; Santiago-Díaz, Carlos; Jiménez-Alonso, Juan

2015-01-20

Autoimmune diseases are a cluster of disorders characterized by a failure of the immune tolerance and a hyperactivation of the immune system that leads to a chronic inflammation state and the damage of several organs. The medications currently used to treat these diseases usually consist of immunosuppressive drugs that have significant systemic toxic effects and are associated with an increased risk of opportunistic infections. Recently, several studies have demonstrated that mesenchymal stem cells have immunomodulatory properties, a feature that make them candidates to be used in the treatment of autoimmune diseases. In the present study, we reviewed the role of this therapy in the treatment of systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, Crohn's disease and multiple sclerosis, as well as the potential risks associated with its use. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

A meta-analysis of observational studies of the association between chronic occupational exposure to lead and amyotrophic lateral sclerosis.

PubMed

Wang, Ming-Dong; Gomes, James; Cashman, Neil R; Little, Julian; Krewski, Daniel

2014-12-01

The association between occupational exposure to lead and amyotrophic lateral sclerosis (ALS) was examined through systematic review and meta-analyses of relevant epidemiological studies and reported according to PRISMA guidelines. Relevant studies were searched in multiple bibliographic databases through September 2013; additional articles were tracked through PubMed until submission. All records were screened in DistillerSR, and the data extracted from included articles were synthesized with meta-analysis. The risk of developing ALS among individuals with a history of exposure to lead was almost doubled (odds ratio, 1.81; 95% confidence interval, 1.39 to 2.36) on the basis of nine included case-control studies with specific lead exposure information, with no apparent heterogeneity across included studies (I = 14%). The attributable risk of ALS because of exposure to lead was estimated to be 5%. Previous exposure to lead may be a risk factor for ALS.

Walking impairment in patients with multiple sclerosis: exercise training as a treatment option.

PubMed

Motl, Robert W; Goldman, Myla D; Benedict, Ralph H B

2010-11-16

Multiple sclerosis (MS) is a chronic disease of the central nervous system that culminates in the progression of physical and cognitive disability over time. Walking impairment is a ubiquitous feature of MS and a sentinel characteristic of the later or advanced stages of the disease. This paper presents a conceptual rationale along with empirical evidence for exercise training as a rehabilitation approach for managing walking impairment and improving walking function in persons with MS. Conceptually, MS is associated with a decrease in physical activity, which, in turn, can result in deconditioning across multiple domains of physiological functioning. The resulting deconditioning feeds back and further drives physical inactivity until a threshold is reached that likely initiates the progression of walking impairment in MS. Empirically, physical activity and exercise training have been associated with beneficial effects on walking function in persons with MS. This is based on cross-sectional, longitudinal, and experimental research that included diversity in the breadth of measures of walking, persons with MS, and exercise/physical activity characteristics. Of particular importance, future researchers might consider examining the combinatory effects of exercise training plus pharmacological agents on walking mobility in MS. Collectively, exercise training and physical activity might hold significant potential for the management of progressive mobility disability in MS.

The effects of prolonged wear of textured shoe insoles on gait, foot sensation and proprioception in people with multiple sclerosis: study protocol for a randomised controlled trial.

PubMed

Hatton, Anna L; Dixon, John; Rome, Keith; Brauer, Sandra G; Williams, Katrina; Kerr, Graham

2016-04-21

Many people with multiple sclerosis experience problems with walking, which can make daily activities difficult and often leads to falls. Foot sensation plays an important role in keeping the body balanced whilst walking; however, people with multiple sclerosis often have poor sensation on the soles of their feet. Wearing a specially designed shoe insole, which enhances plantar sensory information, could help people with multiple sclerosis to walk better. This study will explore whether long-term wear of a textured insole can improve walking in people with multiple sclerosis. A prospective randomised controlled trial with two parallel groups will be conducted aiming to recruit 176 people with multiple sclerosis living in the community (Brisbane, Australia). Adults with a clinical diagnosis of multiple sclerosis, Disease Steps score 1-4, who are ambulant over 100 m and who meet specific inclusion criteria will be recruited. Participants will be randomised to a smooth control insole (n = 88) or textured insole (n = 88) group. The allocated insole will be worn for 12-weeks within participants' own footwear, with self-report wear diaries and falls calendars being completed over this period. Blinded assessors will conduct two baseline assessments and one post-intervention assessment. Gait tasks will be completed barefoot, wearing standardised footwear only, and wearing standardised footwear with smooth and textured insoles. The primary outcome measure will be mediolateral base of support when walking over even and uneven surfaces. Secondary measures include spatiotemporal gait parameters (stride length, stride time variability, double-limb support time, velocity), gait kinematics (hip, knee, and ankle joint angles, toe clearance, trunk inclination, arm swing, mediolateral pelvis/head displacement), foot sensation (light touch-pressure, vibration, two-point discrimination) and proprioception (ankle joint position sense). Group allocation will be concealed and all analyses will be based on an intention-to-treat principle. This study will explore the effects of wearing textured insoles over 12-weeks on gait, foot sensation and proprioception in people with multiple sclerosis. The study has the potential to identify a new, evidence-based footwear intervention which has the capacity to enhance mobility and independent living in people with multiple sclerosis. Australian New Zealand Clinical Trials Registry ACTRN12615000421538 . Registered 4 May 2015.

Neurofilament light chain and oligoclonal bands are prognostic biomarkers in radiologically isolated syndrome.

PubMed

Matute-Blanch, Clara; Villar, Luisa M; Álvarez-Cermeño, José C; Rejdak, Konrad; Evdoshenko, Evgeniy; Makshakov, Gleb; Nazarov, Vladimir; Lapin, Sergey; Midaglia, Luciana; Vidal-Jordana, Angela; Drulovic, Jelena; García-Merino, Antonio; Sánchez-López, Antonio J; Havrdova, Eva; Saiz, Albert; Llufriu, Sara; Alvarez-Lafuente, Roberto; Schroeder, Ina; Zettl, Uwe K; Galimberti, Daniela; Ramió-Torrentà, Lluís; Robles, René; Quintana, Ester; Hegen, Harald; Deisenhammer, Florian; Río, Jordi; Tintoré, Mar; Sánchez, Alex; Montalban, Xavier; Comabella, Manuel

2018-04-01

The prognostic role of cerebrospinal fluid molecular biomarkers determined in early pathogenic stages of multiple sclerosis has yet to be defined. In the present study, we aimed to investigate the prognostic value of chitinase 3 like 1 (CHI3L1), neurofilament light chain, and oligoclonal bands for conversion to clinically isolated syndrome and to multiple sclerosis in 75 patients with radiologically isolated syndrome. Cerebrospinal fluid levels of CHI3L1 and neurofilament light chain were measured by enzyme-linked immunosorbent assay. Uni- and multivariable Cox regression models including as covariates age at diagnosis of radiologically isolated syndrome, number of brain lesions, sex and treatment were used to investigate associations between cerebrospinal fluid CHI3L1 and neurofilament light chain levels and time to conversion to clinically isolated syndrome and multiple sclerosis. Neurofilament light chain levels and oligoclonal bands were independent risk factors for the development of clinically isolated syndrome (hazard ratio = 1.02, P = 0.019, and hazard ratio = 14.7, P = 0.012, respectively) and multiple sclerosis (hazard ratio = 1.03, P = 0.003, and hazard ratio = 8.9, P = 0.046, respectively). The best cut-off to classify cerebrospinal fluid neurofilament light chain levels into high and low was 619 ng/l, and high neurofilament light chain levels were associated with a trend to shorter time to clinically isolated syndrome (P = 0.079) and significant shorter time to multiple sclerosis (P = 0.017). Similarly, patients with radiologically isolated syndrome presenting positive oligoclonal bands converted faster to clinically isolated syndrome and multiple sclerosis (P = 0.005 and P = 0.008, respectively). The effects of high neurofilament light chain levels shortening time to clinically isolated syndrome and multiple sclerosis were more pronounced in radiologically isolated syndrome patients with ≥37 years compared to younger patients. Cerebrospinal fluid CHI3L1 levels did not influence conversion to clinically isolated syndrome and multiple sclerosis in radiologically isolated syndrome patients. Overall, these findings suggest that cerebrospinal neurofilament light chain levels and oligoclonal bands are independent predictors of clinical conversion in patients with radiologically isolated syndrome. The association with a faster development of multiple sclerosis reinforces the importance of cerebrospinal fluid analysis in patients with radiologically isolated syndrome.

MALDI imaging mass spectrometry analysis-A new approach for protein mapping in multiple sclerosis brain lesions.

PubMed

Maccarrone, Giuseppina; Nischwitz, Sandra; Deininger, Sören-Oliver; Hornung, Joachim; König, Fatima Barbara; Stadelmann, Christine; Turck, Christoph W; Weber, Frank

2017-03-15

Multiple sclerosis is a disease of the central nervous system characterized by recurrent inflammatory demyelinating lesions in the early disease stage. Lesion formation and mechanisms leading to lesion remyelination are not fully understood. Matrix Assisted Laser Desorption Ionisation Mass Spectrometry imaging (MALDI-IMS) is a technology which analyses proteins and peptides in tissue, preserves their spatial localization, and generates molecular maps within the tissue section. In a pilot study we employed MALDI imaging mass spectrometry to profile and identify peptides and proteins expressed in normal-appearing white matter, grey matter and multiple sclerosis brain lesions with different extents of remyelination. The unsupervised clustering analysis of the mass spectra generated images which reflected the tissue section morphology in luxol fast blue stain and in myelin basic protein immunohistochemistry. Lesions with low remyelination extent were defined by compounds with molecular weight smaller than 5300Da, while more completely remyelinated lesions showed compounds with molecular weights greater than 15,200Da. An in-depth analysis of the mass spectra enabled the detection of cortical lesions which were not seen by routine luxol fast blue histology. An ion mass, mainly distributed at the rim of multiple sclerosis lesions, was identified by liquid chromatography and tandem mass spectrometry as thymosin beta-4, a protein known to be involved in cell migration and in restorative processes. The ion mass of thymosin beta-4 was profiled by MALDI imaging mass spectrometry in brain slides of 12 multiple sclerosis patients and validated by immunohistochemical analysis. In summary, our results demonstrate the ability of the MALDI-IMS technology to map proteins within the brain parenchyma and multiple sclerosis lesions and to identify potential markers involved in multiple sclerosis pathogenesis and/or remyelination. Copyright © 2016 Elsevier B.V. All rights reserved.

Somatosensory impairment and its association with balance limitation in people with multiple sclerosis.

PubMed

Jamali, Akram; Sadeghi-Demneh, Ebrahim; Fereshtenajad, Niloufar; Hillier, Susan

2017-09-01

Somatosensory impairments are common in multiple sclerosis. However, little data are available to characterize the nature and frequency of these problems in people with multiple sclerosis. To investigate the frequency of somatosensory impairments and identify any association with balance limitations in people with multiple sclerosis. The design was a prospective cross-sectional study, involving 82 people with multiple sclerosis and 30 healthy controls. Tactile and proprioceptive sensory acuity were measured using the Rivermead Assessment of Somatosensory Performance. Vibration duration was assessed using a tuning fork. Duration for the Timed Up and Go Test and reaching distance of the Functional Reach Test were measured to assess balance limitations. The normative range of sensory modalities was defined using cut-off points in the healthy participants. The multivariate linear regression was used to identify the significant predictors of balance in people with multiple sclerosis. Proprioceptive impairments (66.7%) were more common than tactile (60.8%) and vibration impairments (44.9%). Somatosensory impairments were more frequent in the lower limb (78.2%) than the upper limb (64.1%). All sensory modalities were significantly associated with the Timed Up and Go and Functional Reach tests (p<0.05). The Timed Up and Go test was independently predicted by the severity of the neurological lesion, Body Mass Index, ataxia, and tactile sensation (R2=0.58), whereas the Functional Reach test was predicted by the severity of the neurological lesion, lower limb strength, and vibration sense (R2=0.49). Somatosensory impairments are very common in people with multiple sclerosis. These impairments are independent predictors of balance limitation. Copyright © 2017 Elsevier B.V. All rights reserved.

Pediatric multiple sclerosis: current perspectives on health behaviors.

PubMed

Sikes, Elizabeth Morghen; Motl, Robert W; Ness, Jayne M

2018-01-01

Pediatric-onset multiple sclerosis (POMS) accounts for ~5% of all multiple sclerosis cases, and has a prevalence of ~10,000 children in the USA. POMS is associated with a higher relapse rate, and results in irreversible disability on average 10 years earlier than adult-onset multiple sclerosis. Other manifestations of POMS include mental and physical fatigue, cognitive impairment, and depression. We believe that the health behaviors of physical activity, diet, and sleep may have potential benefits in POMS, and present a scoping review of the existing literature. We identified papers by searching three electronic databases (PubMed, GoogleScholar, and CINAHL). Search terms included: pediatric multiple sclerosis OR pediatric onset multiple sclerosis OR POMS AND health behavior OR physical activity OR sleep OR diet OR nutrition OR obesity. Papers were included in this review if they were published in English, referenced nutrition, diet, obesity, sleep, exercise, or physical activity, and included pediatric-onset multiple sclerosis as a primary population. Twenty papers were identified via the literature search that addressed health-promoting behaviors in POMS, and 11, 8, and 3 papers focused on diet, activity, and sleep, respectively. Health-promoting behaviors were associated with markers of disease burden in POMS. Physical activity participation was associated with reduced relapse rate, disease burden, and sleep/rest fatigue symptoms. Nutritional factors, particularly vitamin D intake, may be associated with relapse rate. Obesity has been associated with increased risk of developing POMS. POMS is associated with better sleep hygiene, and this may benefit fatigue and quality of life. Participation in health behaviors, particularly physical activity, diet, and sleep, may have benefits for POMS. Nevertheless, there are currently no interventions targeting promotion of these behaviors and examining the benefits of managing the primary and secondary manifestations of POMS.

Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis.

PubMed

Khavari, Rose; Karmonik, Christof; Shy, Michael; Fletcher, Sophie; Boone, Timothy

2017-02-01

Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction. We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia. Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively. We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas of interest for future intervention. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Occipital neuralgia associates with high cervical spinal cord lesions in idiopathic inflammatory demyelinating disease.

PubMed

Kissoon, Narayan R; Watson, James C; Boes, Christopher J; Kantarci, Orhun H

2018-01-01

Background The association of trigeminal neuralgia with pontine lesions has been well documented in multiple sclerosis, and we tested the hypothesis that occipital neuralgia in multiple sclerosis is associated with high cervical spinal cord lesions. Methods We retrospectively reviewed the records of 29 patients diagnosed with both occipital neuralgia and demyelinating disease by a neurologist from January 2001 to December 2014. We collected data on demographics, clinical findings, presence of C2-3 demyelinating lesions, and treatment responses. Results The patients with both occipital neuralgia and multiple sclerosis were typically female (76%) and had a later onset (age > 40) of occipital neuralgia (72%). Eighteen patients (64%) had the presence of C2-3 lesions and the majority had unilateral symptoms (83%) or episodic pain (78%). All patients with documented sensory loss (3/3) had C2-3 lesions. Most patients with progressive multiple sclerosis (6/8) had C2-3 lesions. Of the eight patients with C2-3 lesions and imaging at onset of occipital neuralgia, five (62.5%) had evidence of active demyelination. None of the patients with progressive multiple sclerosis (3/3) responded to occipital nerve blocks or high dose intravenous steroids, whereas all of the other phenotypes with long term follow-up (eight patients) had good responses. Conclusions A cervical spine MRI should be considered in all patients presenting with occipital neuralgia. In patients with multiple sclerosis, clinical features in occipital neuralgia that were predictive of the presence of a C2-3 lesion were unilateral episodic symptoms, sensory loss, later onset of occipital neuralgia, and progressive multiple sclerosis phenotype. Clinical phenotype predicted response to treatment.

A palliative care hotline for multiple sclerosis: A pilot feasibility study.

PubMed

Knies, Andrea K; Golla, Heidrun; Strupp, Julia; Galushko, Maren; Schipper, Sabine; Voltz, Raymond

2015-08-01

Research findings suggest that patients severely affected by multiple sclerosis benefit from palliative care. Our objectives were to (1) implement a pilot palliative care counseling hotline for severely affected multiple sclerosis patients and their caregivers in order to connect them to palliative care, and (2) evaluate its preliminary feasibility through a pilot study. The hotline was designed in cooperation with the local state association of the German Multiple Sclerosis Society and based on a review of the literature. The initial study setting for the hotline was the broader region of the cities Cologne and Bonn in Germany. The hotline was introduced through a magazine published by the German Multiple Sclerosis Society and leaflets sent to local healthcare providers. Calls were conducted using a semistructured interview guide and documented by a standardized case report form. Measures to assess feasibility were both quantitative (e.g., number of calls) and qualitative (e.g., criteria for eligibility for palliative care). During its pilot year, the hotline received 18 calls. Some 15 callers were included in the analysis, and 10 of these 15 were deemed eligible for palliative care due to such criteria as medical characteristics, care or nursing conditions, caregiver strain, and concerns regarding death and dying. Access to palliative care services could be provided for all 10 callers. Based on our pilot feasibility study, the hotline seems to be a valuable service for patients severely affected by multiple sclerosis (MS) and their caregivers in order to gain information about and access to palliative care. It will be extended on a nationwide scale through a grant of the German Multiple Sclerosis Society. Awareness of the hotline needs to be enhanced in order to attract and support a significant number of new callers.

[Current therapy of multiple sclerosis].

PubMed

Antonio García Merino, J

2014-12-01

Since the introduction of interferon beta 1 b for the treatment of multiple sclerosis, there has been a progressive increase in the number of drugs available for this disease. Currently, 11 drugs have been approved in Spain, and their indications depend on specific clinical characteristics. The present article reviews these indications and also discusses other medications without official approval that have also been used in multiple sclerosis. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Cells, Biomarkers, and Posttraumatic Stress Disorder: Evidence for Peripheral Involvement in a Central Disease

DTIC Science & Technology

2012-01-01

including; Alzheimer’s disease (Mac- cioni et al. 2009), Parkinson’s disease (Hirsch and Hunot 2009), spinal cord injury (Chan 2008), multiple sclerosis ...states such as multiple sclerosis (Kraus et al. 2000), human immunodeficiency virus dementia (Fischer- Smith et al. 2001), and meningitis (Cauwels et al...Immunologic mechanisms of multiple sclerosis . Neuroi- maging Clin. N. Am. 18, 577–588. Gaylord K. M. (2006) The psychosocial effects of combat: the frequently

Gut microbiota in MS: possible influence of immunomodulators

PubMed Central

Cantarel, Brandi L.; Waubant, Emmanuelle; Chehoud, Christel; Kuczynski, Justin; DeSantis, Todd Z.; Warrington, Janet; Venkatesan, Arun; Fraser, Claire M.; Mowry, Ellen M.

2015-01-01

Objectives Differences in gut bacteria have been described in several autoimmune disorders. In this exploratory pilot study, we compared gut bacteria in multiple sclerosis patients and healthy controls and evaluated the influence of glatiramer acetate and vitamin D treatment on the microbiota. Methods Subjects were otherwise healthy white women with or without relapsing-remitting multiple sclerosis who were vitamin D insufficient. Multiple sclerosis patients were untreated or were receiving glatiramer acetate. Subjects collected stool at baseline and after 90 days of vitamin D3 (5,000 IU/day) supplementation. The abundance of operational taxonomic units was evaluated by hybridization of 16S rRNA to a DNA microarray. Results While there was overlap of gut bacterial communities, the abundance of some operational taxonomic units, including Faecalibacterium, was lower in multiple sclerosis patients. Glatiramer acetate-treated MS subjects showed differences in community composition compared to untreated subjects, including Bacteroidaceae, Faecalibacterium, Ruminococcus, Lactobacillaceae, Clostridium, and Other Clostridiales. Compared to the other groups, untreated multiple sclerosis subjects had an increase in the Akkermansia, Faecalibacterium, and Coprococcus genera after vitamin D supplementation. Conclusions While overall bacterial communities were similar, specific operational taxonomic units differed between healthy and multiple sclerosis subjects. Glatiramer acetate and vitamin D supplementation were associated with differences or changes in the microbiota. This study was exploratory, and larger studies are needed to confirm these preliminary results. PMID:25775034

Features of Coping with Disease in Iranian Multiple Sclerosis Patients: a Qualitative Study.

PubMed

Dehghani, Ali; Dehghan Nayeri, Nahid; Ebadi, Abbas

2018-03-01

Introduction: Coping with disease is of the main components improving the quality of life in multiple sclerosis patients. Identifying the characteristics of this concept is based on the experiences of patients. Using qualitative research is essential to improve the quality of life. This study was conducted to explore the features of coping with the disease in patients with multiple sclerosis. Method: In this conventional content analysis study, eleven multiple sclerosis patients from Iran MS Society in Tehran (Iran) participated. Purposive sampling was used to select participants. Data were gathered using semi structured interviews. To analyze data, a conventional content analysis approach was used to identify meaning units and to make codes and categories. Results: Results showed that features of coping with disease in multiple sclerosis patients consists of (a) accepting the current situation, (b) maintenance and development of human interactions, (c) self-regulation and (d) self-efficacy. Each of these categories is composed of sub-categories and codes that showed the perception and experience of patients about the coping with disease. Conclusion: Accordingly, a unique set of features regarding features of coping with the disease were identified among the patients with multiple sclerosis. Therefore, working to ensure the emergence of, and subsequent reinforcement of these features in MS patients can be an important step in improving the adjustment and quality of their lives.

A regenerative approach to the treatment of multiple sclerosis.

PubMed

Deshmukh, Vishal A; Tardif, Virginie; Lyssiotis, Costas A; Green, Chelsea C; Kerman, Bilal; Kim, Hyung Joon; Padmanabhan, Krishnan; Swoboda, Jonathan G; Ahmad, Insha; Kondo, Toru; Gage, Fred H; Theofilopoulos, Argyrios N; Lawson, Brian R; Schultz, Peter G; Lairson, Luke L

2013-10-17

Progressive phases of multiple sclerosis are associated with inhibited differentiation of the progenitor cell population that generates the mature oligodendrocytes required for remyelination and disease remission. To identify selective inducers of oligodendrocyte differentiation, we performed an image-based screen for myelin basic protein (MBP) expression using primary rat optic-nerve-derived progenitor cells. Here we show that among the most effective compounds identifed was benztropine, which significantly decreases clinical severity in the experimental autoimmune encephalomyelitis (EAE) model of relapsing-remitting multiple sclerosis when administered alone or in combination with approved immunosuppressive treatments for multiple sclerosis. Evidence from a cuprizone-induced model of demyelination, in vitro and in vivo T-cell assays and EAE adoptive transfer experiments indicated that the observed efficacy of this drug results directly from an enhancement of remyelination rather than immune suppression. Pharmacological studies indicate that benztropine functions by a mechanism that involves direct antagonism of M1 and/or M3 muscarinic receptors. These studies should facilitate the development of effective new therapies for the treatment of multiple sclerosis that complement established immunosuppressive approaches.

Effects of physiotherapy treatment for urinary incontinence in patient with multiple sclerosis.

PubMed

Pereira, Carla Maria de Abreu; Castiglione, Mariane; Kasawara, Karina Tamy

2017-07-01

[Purpose] The aim of the study was to evaluate the benefits of physical therapy for urinary incontinence in patients with multiple sclerosis and to verify the impact of urinary incontinence on the patient's quality of life. [Subject and Methods] A case study of a 55-year-old female patient diagnosed with multiple sclerosis and mixed urinary incontinence was conducted. Physical therapy sessions were conducted once a week, in total 15 sessions, making use of targeted functional electrical vaginal stimulation, along with active exercises for the pelvic floor muscles and electrical stimulation of the posterior tibial nerve, behavioral rehabilitation and exercise at home. [Results] After 15 physical therapy sessions, a patient diagnosed with multiple sclerosis and mixed urinary incontinence showed continued satisfactory results after five months. She showed better quality of life, higher strength of pelvic floor muscle and reduced urinary frequency without nocturia and enuresis. [Conclusion] The physical therapy protocol in this patient with multiple sclerosis and mixed urinary incontinence showed satisfactory results reducing urinary incontinence symptomatology and improving the patient's quality of life.

Disability and Fatigue Can Be Objectively Measured in Multiple Sclerosis.

PubMed

Motta, Caterina; Palermo, Eduardo; Studer, Valeria; Germanotta, Marco; Germani, Giorgio; Centonze, Diego; Cappa, Paolo; Rossi, Silvia; Rossi, Stefano

2016-01-01

The available clinical outcome measures of disability in multiple sclerosis are not adequately responsive or sensitive. To investigate the feasibility of inertial sensor-based gait analysis in multiple sclerosis. A cross-sectional study of 80 multiple sclerosis patients and 50 healthy controls was performed. Lower-limb kinematics was evaluated by using a commercially available magnetic inertial measurement unit system. Mean and standard deviation of range of motion (mROM, sROM) for each joint of lower limbs were calculated in one minute walking test. A motor performance index (E) defined as the sum of sROMs was proposed. We established two novel observer-independent measures of disability. Hip mROM was extremely sensitive in measuring lower limb motor impairment, being correlated with muscle strength and also altered in patients without clinically detectable disability. On the other hand, E index discriminated patients according to disability, being altered only in patients with moderate and severe disability, regardless of walking speed. It was strongly correlated with fatigue and patient-perceived health status. Inertial sensor-based gait analysis is feasible and can detect clinical and subclinical disability in multiple sclerosis.

The Impact of Exercise Training on Living Quality in Multiple Sclerosis Individuals

ClinicalTrials.gov

2017-08-27

Multiple Sclerosis; Fatigue; Mental Status Change; Physical Disability; Physical Activity; Mental Impairment; Quality of Life; Disabilities Psychological; Disability Physical; Pain; Energy Supply; Deficiency; Motivation

European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS) - 7th Joint Triennial Congress (October 25-28, 2017 - Paris, France).

PubMed

Díaz, N

2017-10-01

The 7th Triennial Joint conference of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) was held in Paris, France. The meeting brought together attendees from a wide range of disciplines involved in multiple sclerosis (MS) research to explore an extensive program of teaching courses, plenary lectures, oral and poster sessions from approximately 2,000 abstracts submitted, and hot topic and young investigator presentations. These presentations covered topics including diagnostics, therapeutics and biomarkers, as well as a special section for MS nurses. Industry-sponsored symposia were also held. The report from this conference covers the latest developments in MS treatments.

How do immune cells support and shape the brain in health, disease, and aging?

PubMed

Schwartz, Michal; Kipnis, Jonathan; Rivest, Serge; Prat, Alexandre

2013-11-06

For decades, several axioms have prevailed with respect to the relationships between the CNS and circulating immune cells. Specifically, immune cell entry was largely considered to be pathological or to mark the beginning of pathology within the brain. Moreover, local inflammation associated with neurodegenerative diseases such Alzheimer's disease or amyotrophic lateral sclerosis, were considered similar in their etiology to inflammatory diseases, such as remitting relapsing-multiple sclerosis. The ensuing confusion reflected a lack of awareness that the etiology of the disease as well as the origin of the immune cells determines the nature of the inflammatory response, and that inflammation resolution is an active cellular process. The last two decades have seen a revolution in these prevailing dogmas, with a significant contribution made by the authors. Microglia and infiltrating monocyte-derived macrophages are now known to be functionally distinct and of separate origin. Innate and adaptive immune cells are now known to have protective/healing properties in the CNS, as long as their activity is regulated, and their recruitment is well controlled; their role is appreciated in maintenance of brain plasticity in health, aging, and chronic neurodevelopmental and neurodegenerative diseases. Moreover, it is now understood that the barriers of the brain are not uniform in their interactions with the circulating immune cells. The implications of these new findings to the basic understanding of CNS repair processes, brain aging, and a wide spectrum of CNS disorders, including acute injuries, Rett syndrome, Alzheimer's disease, and multiple sclerosis, will be discussed.

Pharmacological treatments for fatigue in patients with multiple sclerosis: A systematic review and meta-analysis.

PubMed

Yang, Ting-Ting; Wang, Li; Deng, Xiao-Yang; Yu, Gang

2017-09-15

Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disease. Fatigue is the most common symptom of MS patients, affecting >80% subjects. Medical treatment is an important method for managing fatigue. Currently, although many drugs have been tested in treatment of MS fatigue, the efficacy of these drugs remain largely unclear. We researched available literatures in PubMed, Embase, Medline, Google Scholar, Cochrane Library (August 31, 2016). Search terms included multiple sclerosis, fatigue, medication treatments, amantadine, modafinil, aspirin, acetyl-l-carnitine, pemoline, 4-aminopyridine and randomized controlled trial (RCT). Two researchers were required to independently assess the quality of literatures, and finish data extraction. Meta-analysis was conducted using RevMan 5.3 software. A total of 11 RCTs involving 723 patients were included. The therapeutic effects were quantified by different scales, such as Modified Fatigue Impact Scale (MFIS) or Fatigue Severity Scale (FSS). Here, meta-analysis suggested that amantadine, not modafinil, was effective for treating the fatigue in MS. Moreover, two studies implied that l-carnitine might have similar therapeutic effect with amantadine. However, the reliability of this finding was greatly weakened by the limited sample sizes. Additionally, current data could not answer whether treatment of MS fatigue using aspirin or 4-aminopyridine was beneficial. Finally, we found that all drugs except pemoline were relatively safe for treating MS fatigue. Current limited data suggest that amantadine may be the only drug that has relatively sufficient evidences in treatment of fatigue symptoms in MS. Further RCT studies recruiting larger samples sizes are required to validate the therapeutic effect of these candidate drugs. Copyright © 2017. Published by Elsevier B.V.

Spondyloarthritis, Acute Anterior Uveitis, and Fungi: Updating the Catterall–King Hypothesis

PubMed Central

Laurence, Martin; Asquith, Mark; Rosenbaum, James T.

2018-01-01

Spondyloarthritis is a common type of arthritis which affects mostly adults. It consists of idiopathic chronic inflammation of the spine, joints, eyes, skin, gut, and prostate. Inflammation is often asymptomatic, especially in the gut and prostate. The HLA-B*27 allele group, which presents intracellular peptides to CD8+ T cells, is by far the strongest risk factor for spondyloarthritis. The precise mechanisms and antigens remain unknown. In 1959, Catterall and King advanced a novel hypothesis explaining the etiology of spondyloarthritis: an as-yet-unrecognized sexually acquired microbe would be causing all spondyloarthritis types, including acute anterior uveitis. Recent studies suggest an unrecognized sexually acquired fungal infection may be involved in prostate cancer and perhaps multiple sclerosis. This warrants reanalyzing the Catterall–King hypothesis based on the current literature. In the last decade, many links between spondyloarthritis and fungal infections have been found. Antibodies against the fungal cell wall component mannan are elevated in spondyloarthritis. Functional polymorphisms in genes regulating the innate immune response against fungi have been associated with spondyloarthritis (CARD9 and IL23R). Psoriasis and inflammatory bowel disease, two common comorbidities of spondyloarthritis, are both strongly associated with fungi. Evidence reviewed here lends credence to the Catterall–King hypothesis and implicates a common fungal etiology in prostate cancer, benign prostatic hyperplasia, multiple sclerosis, psoriasis, inflammatory bowel disease, and spondyloarthritis. However, the evidence available at this time is insufficient to definitely confirm this hypothesis. Future studies investigating the microbiome in relation to these conditions should screen specimens for fungi in addition to bacteria. Future clinical studies of spondyloarthritis should consider antifungals which are effective in psoriasis and multiple sclerosis, such as dimethyl fumarate and nystatin. PMID:29675414

Coenzyme Q10 as a treatment for fatigue and depression in multiple sclerosis patients: A double blind randomized clinical trial.

PubMed

Sanoobar, Meisam; Dehghan, Parvin; Khalili, Mohammad; Azimi, Amirreza; Seifar, Fatemeh

2016-01-01

Multiple sclerosis (MS) is the chronic inflammatory and demyelinating disorder of central nervous system which is accompanied with disability and negative life style changes such as fatigue and depression. The aim of this study is to investigate the effect of coenzyme Q10 (CoQ10) supplementation on fatigue and depression in patients with MS. We performed a randomized, double-blinded, placebo-controlled trial to determine the effect of CoQ10 supplement (500 mg/day) vs. placebo for 12 weeks. Fatigue symptoms were quantified by means of fatigue severity scale (FSS) and the Beck depression inventory (BDI) was used to assess depressive symptoms. A significant decrease of FSS was observed in CoQ10 group during the intervention (P = 0.001) and significant increase of FSS change was observed within placebo group (P = 0.001). Repeated measure analysis of variance showed a significant time-by-treatment interaction for FSS (baseline 41.5 ± 15.6 vs. endpoint 45 ± 13.6; F1,45 = 55.23, P < 0.001, η(2) = 0.56) and BDI (baseline 17.8 ± 12.2 vs. endpoint 20.4 ± 11.4; F1,45 = 40.3, P < 0.001, η(2) = 0.48), indicating significant decrease of FSS and BDI in CoQ10 group compared to placebo group. Our study suggests that CoQ10 supplementation (500 mg/day) can improve fatigue and depression in patients with multiple sclerosis.

TRPA1 deficiency is protective in cuprizone-induced demyelination-A new target against oligodendrocyte apoptosis.

PubMed

Sághy, Éva; Sipos, Éva; Ács, Péter; Bölcskei, Kata; Pohóczky, Krisztina; Kemény, Ágnes; Sándor, Zoltán; Szőke, Éva; Sétáló, György; Komoly, Sámuel; Pintér, Erika

2016-12-01

Multiple sclerosis is a chronic inflammatory, demyelinating degenerative disease of the central nervous system. Current treatments target pathological immune responses to counteract the inflammatory processes. However, these drugs do not restrain the long-term progression of clinical disability. For this reason, new therapeutic approaches and identification of novel target molecules are needed to prevent demyelination or promote repair mechanisms. Transient Receptor Potential Ankyrin 1 (TRPA1) is a nonselective cation channel with relatively high Ca 2+ permeability. Its pathophysiological role in central nervous system disorders has not been elucidated yet. In the present study, we aimed to assess the distribution of TRPA1 in the mouse brain and reveal its regulatory role in the cuprizone-induced demyelination. This toxin-induced model, characterized by oligodendrocyte apoptosis and subsequent primary demyelination, allows us to investigate the nonimmune aspects of multiple sclerosis. We found that TRPA1 is expressed on astrocytes in the mouse central nervous system. Interestingly, TRPA1 deficiency significantly attenuated cuprizone-induced demyelination by reducing the apoptosis of mature oligodendrocytes. Our data suggest that TRPA1 regulates mitogen-activated protein kinase pathways, as well as transcription factor c-Jun and a proapoptotic Bcl-2 family member (Bak) expression resulting in enhanced oligodendrocyte apoptosis. In conclusion, we propose that TRPA1 receptors enhancing the intracellular Ca 2+ concentration modulate astrocyte functions, and influence the pro or anti-apoptotic pathways in oligodendrocytes. Inhibition of TRPA1 receptors might successfully diminish the degenerative pathology in multiple sclerosis and could be a promising therapeutic target to limit central nervous system damage in demyelinating diseases. GLIA 2016;64:2166-2180. © 2016 Wiley Periodicals, Inc.

Changes in Th17 cells function after nanocurcumin use to treat multiple sclerosis.

PubMed

Dolati, Sanam; Ahmadi, Majid; Rikhtegar, Reza; Babaloo, Zohreh; Ayromlou, Hormoz; Aghebati-Maleki, Leili; Nouri, Mohammad; Yousefi, Mehdi

2018-05-28

MS is a chronic inflammatory disease that causes to brain inflammation and Th17 cells are considered to be important in multiple sclerosis pathogenesis. In the current study, we aimed to identify nanocurcumin effects on Th17 cells frequency, cytokines secretion, and expression of transcription factor of patients with relapsing-remitting multiple sclerosis (RRMS). In this study we investigated frequency of Th17 lymphocytes; the expression of transcription factor, associated cytokines and the concentration of them in 35 healthy controls, and from 25 patients at baseline and after 6 months of nanocurcumin treatment and also from 25 patients whose received placebo by flowcytometry, real-time PCR and ELISA, respectively. Our analysis revealed that the proportions of Th17 were increased dramatically, along with increases in the levels of IL-17A, IL-23, and RORγt expression in MS patients in compared with healthy control group. Post-treatment evaluation of the nanocurcumin group revealed a significant decrease in Th17 associated parameters such as Th17 frequency (p = 0.029), expression levels of RORγt (p < 0.0001) and IL-17 (p = 0.0044) and also secretion level of IL-17 (p = 0.0011), but IL-23 mRNA expression levels and IL-23 concentration were not influenced by nanocurcumin. However, in the placebo group there is no significant changes in these factors. Our study suggests that the increase in proportion of Th17 cells might contribute to the pathogenesis of RRMS. The results of the current work indicated that nanocurcumin is able to restore the dysregulated of Th17 cells in MS patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Multiple sclerosis and extract of cannabis: results of the MUSEC trial.

PubMed

Zajicek, John Peter; Hobart, Jeremy C; Slade, Anita; Barnes, David; Mattison, Paul G

2012-11-01

Multiple sclerosis (MS) is associated with chronic symptoms, including muscle stiffness, spasms, pain and insomnia. Here we report the results of the Multiple Sclerosis and Extract of Cannabis (MUSEC) study that aimed to substantiate the patient based findings of previous studies. Patients with stable MS at 22 UK centres were randomised to oral cannabis extract (CE) (N=144) or placebo (N=135), stratified by centre, walking ability and use of antispastic medication. This double blind, placebo controlled, phase III study had a screening period, a 2 week dose titration phase from 5 mg to a maximum of 25 mg of tetrahydrocannabinol daily and a 10 week maintenance phase. The primary outcome measure was a category rating scale (CRS) measuring patient reported change in muscle stiffness from baseline. Further CRSs assessed body pain, spasms and sleep quality. Three validated MS specific patient reported outcome measures assessed aspects of spasticity, physical and psychological impact, and walking ability. The rate of relief from muscle stiffness after 12 weeks was almost twice as high with CE than with placebo (29.4% vs. 15.7%; OR 2.26; 95% CI 1.24 to 4.13; p=0.004, one sided). Similar results were found after 4 weeks and 8 weeks, and also for all further CRSs. Results from the MS scales supported these findings. The study met its primary objective to demonstrate the superiority of CE over placebo in the treatment of muscle stiffness in MS. This was supported by results for secondary efficacy variables. Adverse events in participants treated with CE were consistent with the known side effects of cannabinoids. No new safety concerns were observed. NCT00552604.

Comparison of Personal Resources in Patients Who Differently Estimate the Impact of Multiple Sclerosis.

PubMed

Wilski, Maciej; Tomczak, Maciej

2017-04-01

Discrepancies between physicians' assessment and patients' subjective representations of the disease severity may influence physician-patient communication and management of a chronic illness, such as multiple sclerosis (MS). For these reasons, it is important to recognize factors that distinguish patients who differently estimate the impact of MS. The purpose of this study was to verify if the patients who overestimate or underestimate the impact of MS differ in their perception of personal resources from individuals presenting with a realistic appraisal of their physical condition. A total of 172 women and 92 men diagnosed with MS completed Multiple Sclerosis Impact Scale, University of Washington Self Efficacy Scale, Rosenberg Self-Esteem Scale, Body Esteem Scale, Brief Illness Perception Questionnaire, Treatment Beliefs Scale, Actually Received Support Scale, and Socioeconomic resources scale. Physician's assessment of health status was determined with Expanded Disability Status Scale. Linear regression analysis was conducted to identify the subsets of patients with various patterns of subjective health and Expanded Disability Status Scale (EDSS) scores. Patients overestimating the impact of their disease presented with significantly lower levels of self-esteem, self-efficacy in MS, and body esteem; furthermore, they perceived their condition more threatening than did realists and underestimators. They also assessed anti-MS treatment worse, had less socioeconomic resources, and received less support than underestimators. Additionally, underestimators presented with significantly better perception of their disease, self, and body than did realists. Self-assessment of MS-related symptoms is associated with specific perception of personal resources in coping with the disease. These findings may facilitate communication with patients and point to new directions for future research on adaptation to MS.

Neuro-immune interactions at barrier surfaces

PubMed Central

Veiga-Fernandes, Henrique; Mucida, Daniel

2016-01-01

Multidirectional interactions between the nervous and immune systems have been documented in homeostasis and pathologies ranging from multiple sclerosis to autism, and from leukemia to acute and chronic inflammation. Recent studies have addressed this crosstalk using cell-specific targeting, novel sequencing, imaging and analytical tools, shedding light on unappreciated mechanisms of neuro-immune regulation. This review focuses on neuro-immune interactions at barrier surfaces, mostly the gut, but also including the skin and the airways, areas densely populated by neurons and immune cells that constantly sense and adapt to tissue-specific environmental challenges. PMID:27153494

The US Network of Pediatric Multiple Sclerosis Centers: Development, Progress, and Next Steps.

PubMed

Casper, T Charles; Rose, John W; Roalstad, Shelly; Waubant, Emmanuelle; Aaen, Gregory; Belman, Anita; Chitnis, Tanuja; Gorman, Mark; Krupp, Lauren; Lotze, Timothy E; Ness, Jayne; Patterson, Marc; Rodriguez, Moses; Weinstock-Guttman, Bianca; Browning, Brittan; Graves, Jennifer; Tillema, Jan-Mendelt; Benson, Leslie; Harris, Yolanda

2015-09-01

Multiple sclerosis and other demyelinating diseases in the pediatric population have received an increasing level of attention by clinicians and researchers. The low incidence of these diseases in children creates a need for the involvement of multiple clinical centers in research efforts. The Network of Pediatric Multiple Sclerosis Centers was created initially in 2006 to improve the diagnosis and care of children with demyelinating diseases. In 2010, the Network shifted its focus to multicenter research while continuing to advance the care of patients. The Network has obtained support from the National Multiple Sclerosis Society, the Guthy-Jackson Charitable Foundation, and the National Institutes of Health. The Network will continue to serve as a platform for conducting impactful research in pediatric demyelinating diseases of the central nervous system. This article provides a description of the history and development, organization, mission, research priorities, current studies, and future plans of the Network. © The Author(s) 2014.

Cell-based therapeutic strategies for multiple sclerosis

PubMed Central

Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A; Atkins, Harold; Banwell, Brenda; Bar-Or, Amit; Bebo, Bruce; Bowen, James; Burt, Richard; Calabresi, Peter; Cohen, Jeffrey; Comi, Giancarlo; Connick, Peter; Cross, Anne; Cutter, Gary; Derfuss, Tobias; Ffrench-Constant, Charles; Freedman, Mark; Galipeau, Jacques; Goldman, Myla; Goldman, Steven; Goodman, Andrew; Green, Ari; Griffith, Linda; Hartung, Hans-Peter; Hemmer, Bernhard; Hyun, Insoo; Iacobaeus, Ellen; Inglese, Matilde; Jubelt, Burk; Karussis, Dimitrios; Küry, Patrick; Landsman, Douglas; Laule, Cornelia; Liblau, Roland; Mancardi, Giovanni; Ann Marrie, Ruth; Miller, Aaron; Miller, Robert; Miller, David; Mowry, Ellen; Muraro, Paolo; Nash, Richard; Ontaneda, Daniel; Pasquini, Marcelo; Pelletier, Daniel; Peruzzotti-Jametti, Luca; Pluchino, Stefano; Racke, Michael; Reingold, Stephen; Rice, Claire; Ringdén, Olle; Rovira, Alex; Saccardi, Riccardo; Sadiq, Saud; Sarantopoulos, Stefanie; Savitz, Sean; Scolding, Neil; Soelberg Sorensen, Per; Pia Sormani, Maria; Stuve, Olaf; Tesar, Paul; Thompson, Alan; Trojano, Maria; Uccelli, Antonio; Uitdehaag, Bernard; Utz, Ursula; Vukusic, Sandra; Waubant, Emmanuelle; Wilkins, Alastair

2017-01-01

Abstract The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. PMID:29053779

The US Network of Pediatric Multiple Sclerosis Centers: Development, Progress, and Next Steps

PubMed Central

Casper, T. Charles; Rose, John W.; Roalstad, Shelly; Waubant, Emmanuelle; Aaen, Gregory; Belman, Anita; Chitnis, Tanuja; Gorman, Mark; Krupp, Lauren; Lotze, Timothy E.; Ness, Jayne; Patterson, Marc; Rodriguez, Moses; Weinstock-Guttman, Bianca; Browning, Brittan; Graves, Jennifer; Tillema, Jan-Mendelt; Benson, Leslie; Harris, Yolanda

2014-01-01

Multiple sclerosis and other demyelinating diseases in the pediatric population have received an increasing level of attention by clinicians and researchers. The low incidence of these diseases in children creates a need for the involvement of multiple clinical centers in research efforts. The Network of Pediatric Multiple Sclerosis Centers was created initially in 2006 to improve the diagnosis and care of children with demyelinating diseases. In 2010, the Network shifted its focus to multicenter research while continuing to advance the care of patients. The Network has obtained support from the National Multiple Sclerosis Society, the Guthy-Jackson Charitable Foundation, and the National Institutes of Health. The Network will continue to serve as a platform for conducting impactful research in pediatric demyelinating diseases of the central nervous system. This article provides a description of the history and development, organization, mission, research priorities, current studies, and future plans of the Network. PMID:25270659

Permeability of the blood-brain barrier predicts conversion from optic neuritis to multiple sclerosis.

PubMed

Cramer, Stig P; Modvig, Signe; Simonsen, Helle J; Frederiksen, Jette L; Larsson, Henrik B W

2015-09-01

Optic neuritis is an acute inflammatory condition that is highly associated with multiple sclerosis. Currently, the best predictor of future development of multiple sclerosis is the number of T2 lesions visualized by magnetic resonance imaging. Previous research has found abnormalities in the permeability of the blood-brain barrier in normal-appearing white matter of patients with multiple sclerosis and here, for the first time, we present a study on the capability of blood-brain barrier permeability in predicting conversion from optic neuritis to multiple sclerosis and a direct comparison with cerebrospinal fluid markers of inflammation, cellular trafficking and blood-brain barrier breakdown. To this end, we applied dynamic contrast-enhanced magnetic resonance imaging at 3 T to measure blood-brain barrier permeability in 39 patients with monosymptomatic optic neuritis, all referred for imaging as part of the diagnostic work-up at time of diagnosis. Eighteen healthy controls were included for comparison. Patients had magnetic resonance imaging and lumbar puncture performed within 4 weeks of onset of optic neuritis. Information on multiple sclerosis conversion was acquired from hospital records 2 years after optic neuritis onset. Logistic regression analysis showed that baseline permeability in normal-appearing white matter significantly improved prediction of multiple sclerosis conversion (according to the 2010 revised McDonald diagnostic criteria) within 2 years compared to T2 lesion count alone. There was no correlation between permeability and T2 lesion count. An increase in permeability in normal-appearing white matter of 0.1 ml/100 g/min increased the risk of multiple sclerosis 8.5 times whereas having more than nine T2 lesions increased the risk 52.6 times. Receiver operating characteristic curve analysis of permeability in normal-appearing white matter gave a cut-off of 0.13 ml/100 g/min, which predicted conversion to multiple sclerosis with a sensitivity of 88% and specificity of 72%. We found a significant correlation between permeability and the leucocyte count in cerebrospinal fluid as well as levels of CXCL10 and MMP9 in the cerebrospinal fluid. These findings suggest that blood-brain barrier permeability, as measured by magnetic resonance imaging, may provide novel pathological information as a marker of neuroinflammation related to multiple sclerosis, to some extent reflecting cellular permeability of the blood-brain barrier, whereas T2 lesion count may more reflect the length of the subclinical pre-relapse phase.See Naismith and Cross (doi:10.1093/brain/awv196) for a scientific commentary on this article. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Fingolimod

MedlinePlus

... symptoms flare up from time to time) of multiple sclerosis (MS; a disease in which the nerves do ... take your first dose.Fingolimod may help control multiple sclerosis but will not cure it. Do not stop ...

Riboflavin

MedlinePlus

... and nails, to slow aging, for canker sores, multiple sclerosis, memory loss including Alzheimer's disease, high blood pressure, ... the risk of liver cancer in older people. Multiple sclerosis. Early research shows that taking riboflavin by mouth ...

Teriflunomide

MedlinePlus

... symptoms flare up from time to time) of multiple sclerosis (MS; a disease in which the nerves do ... doctor.Teriflunomide may help control the symptoms of multiple sclerosis but does not cure it. Continue to take ...

Dalfampridine

MedlinePlus

... used to improve walking in people who have multiple sclerosis (MS; a disease in which the nerves do ... weakness back pain difficulty with balance worsening of multiple sclerosis symptoms burning, tingling, or itching of the skin ...

Cognitive Impairment in MS Linked to Structural and Functional Connectivity

DTIC Science & Technology

2016-10-01

AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Multiple sclerosis (MS) is the most...9 9. Appendices……………………………………………………………9 Krupp MS130103  2  Abstract Multiple sclerosis (MS) is the most common progressive neurologic...This symptom represents a major concern for many individuals living with multiple sclerosis (MS). Unfortunately, no reliable treatments exist to

Sensory Function and Chronic Pain in Multiple Sclerosis

PubMed Central

Scherder, Rogier J.; Kant, Neeltje; Wolf, Evelien T.; Pijnenburg, Bas C. M.

2018-01-01

Objective To examine whether hypoesthesia and chronic pain are related in patients with MS. Methods Sixty-seven MS patients with pain and 80 persons without MS were included. Sensory functioning was tested by bedside neurological examination. Touch, joint position (dorsal column-medial lemniscus pathway), temperature sense, and pain (spinothalamic tract) were tested. Pain intensity was measured by the Colored Analogue Scale (CAS Intensity) and the Faces Pain Scale (FPS); pain affect was also measured by CAS Affect and Number of Words Chosen-Affective (NWC-A). Mood was assessed with the SCL-90 anxiety and depression subscales and the Beck Depression Inventory (BDI). Results A significant negative relationship was found between pain intensity and the function of the dorsal column-medial lemniscal pathway, but not with the spinothalamic tract. Conclusion In addition to the already known relation between hyperesthesia and pain, hypoesthesia for touch and joint position also seems to be related to chronic pain in MS patients. PMID:29849839

Traumatic brain injury: a risk factor for neurodegenerative diseases.

PubMed

Gupta, Rajaneesh; Sen, Nilkantha

2016-01-01

Traumatic brain injury (TBI), a major global health and socioeconomic problem, is now established as a chronic disease process with a broad spectrum of pathophysiological symptoms followed by long-term disabilities. It triggers multiple and multidirectional biochemical events that lead to neurodegeneration and cognitive impairment. Recent studies have presented strong evidence that patients with TBI history have a tendency to develop proteinopathy, which is the pathophysiological feature of neurodegenerative disorders such as Alzheimer disease (AD), chronic traumatic encephalopathy (CTE), and amyotrophic lateral sclerosis (ALS). This review mainly focuses on mechanisms related to AD, CTE, and ALS that are induced after TBI and their relevance to the advancement of these neurodegenerative diseases. This review encompasses acute effects and chronic neurodegenerative consequences after TBI for a better understanding of TBI-induced neuronal death and to design therapies that will effectively treat patients in the primary or secondary progressive stages.

Neuromyelitis Optica

MedlinePlus

... from cell to cell. NMO is different from multiple sclerosis (MS). Attacks are usually more severe in NMO ... from cell to cell. NMO is different from multiple sclerosis (MS). Attacks are usually more severe in NMO ...

Ocrelizumab Injection

MedlinePlus

... forms (symptoms gradually become worse over time) of multiple sclerosis (MS; a disease in which the nerves do ... or medical facility.Ocrelizumab may help to control multiple sclerosis symptoms, but does not cure it. Your doctor ...

Swallowing problems

MedlinePlus

... Read More Brain aneurysm repair Brain surgery Laryngectomy Multiple sclerosis Oral cancer Parkinson disease Stroke Throat or larynx ... Jejunostomy feeding tube Mouth and neck radiation - discharge Multiple sclerosis - discharge Stroke - discharge Review Date 5/11/2016 ...

Cerebellar Degeneration

MedlinePlus

... cause inflammation in the brain, including the cerebellum multiple sclerosis, in which damage to the insulating membrane (myelin) ... cause inflammation in the brain, including the cerebellum multiple sclerosis, in which damage to the insulating membrane (myelin) ...

Glatiramer Injection

MedlinePlus

... symptoms flare up from time to time) of multiple sclerosis (MS; a disease in which the nerves do ... minutes, but do not rub it. Glatiramer controls multiple sclerosis but does not cure it. Continue to use ...

Foot Drop

MedlinePlus

... muscular problems, such as multiple sclerosis, stroke, and cerebral palsy; motor neuron disorders such as polio, some forms ... muscular problems, such as multiple sclerosis, stroke, and cerebral palsy; motor neuron disorders such as polio, some forms ...

CSF oligoclonal banding

MedlinePlus

... oligoclonal bands may point to a diagnosis of multiple sclerosis. How the Test is Performed A sample of ... Performed This test helps support the diagnosis of multiple sclerosis (MS). However, it does not confirm the diagnosis. ...

Central Pain Syndrome

MedlinePlus

... cord. This syndrome can be caused by stroke, multiple sclerosis, tumors, epilepsy, brain or spinal cord trauma, or ... cord. This syndrome can be caused by stroke, multiple sclerosis, tumors, epilepsy, brain or spinal cord trauma, or ...

Thoracic Outlet Syndrome

MedlinePlus

... including rotator cuff injuries, cervical disc disorders, fibromyalgia, multiple sclerosis, complex regional pain syndrome, and tumors of the ... including rotator cuff injuries, cervical disc disorders, fibromyalgia, multiple sclerosis, complex regional pain syndrome, and tumors of the ...

Stiff-Person Syndrome

MedlinePlus

... The disorder is often misdiagnosed as Parkinson’s disease, multiple sclerosis, fibromyalgia, psychosomatic illness, or anxiety and phobia. A ... The disorder is often misdiagnosed as Parkinson’s disease, multiple sclerosis, fibromyalgia, psychosomatic illness, or anxiety and phobia. A ...

CSF myelin basic protein

MedlinePlus

... done to see if myelin is breaking down. Multiple sclerosis is the most common cause for this, but ... tap) References Fabian MT, Krieger SC, Lublin FD. Multiple sclerosis and other inflammatory demyelinating diseases of the central ...

Technique Selectively Represses Immune System

MedlinePlus

... from attacking myelin in a mouse model of multiple sclerosis. Dr David Furness, Wellcome Images. All rights reserved ... devised a way to successfully treat symptoms resembling multiple sclerosis in a mouse model. With further development, the ...

Brown-Sequard Syndrome

MedlinePlus

... infectious or inflammatory diseases such as tuberculosis, or multiple sclerosis. × Definition Brown-Sequard syndrome (BSS) is a rare ... infectious or inflammatory diseases such as tuberculosis, or multiple sclerosis. View Full Definition Treatment Generally treatment for individuals ...

Daily bowel care program

MedlinePlus

... a brain or spinal cord injury. People with multiple sclerosis also have problems with their bowels. Those with ... PA: Elsevier Saunders; 2016:chap 18. Read More Multiple sclerosis Recovering after stroke Patient Instructions Constipation - self-care ...

Infectious mononucleosis and multiple sclerosis - Updated review on associated risk.

PubMed

Sheik-Ali, Sharaf

2017-05-01

There has been substantial evidence accumulating on the role of infectious mononucleosis (IM) and the subsequent risk of obtaining Multiple Sclerosis (MS). Up to date studies not previously explored were reviewed by the author to further clarify the association. Medline and Web of Science were searched with no time constraints for articles exploring an association between Multiple Sclerosis and Infectious Mononucleosis. 24 articles were found, totalling 1063 cases and 13,227 cohort/controls. 23/24 (96%) articles reported a significant association of Infectious Mononucleosis on the risk of subsequent multiple sclerosis. Overall, new literature on IM and risk of MS categorically supports the association. Future work should focus on other risk factors such as age and gender on IM and subsequent risk of MS. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Learned helplessness in the multiple sclerosis population.

PubMed

McGuinness, S

1996-06-01

The purpose of this cross-sectional, descriptive study was to describe the relationships between learned helplessness and disease status, functional and social disability, and disease activity in the multiple sclerosis population. Additionally, the relationships between learned helplessness and age, disease duration, education and marital and employment status were evaluated. Self-report instruments with established validity and reliability in the multiple sclerosis population were used to collect the data. Learned helplessness was significantly positively correlated with social and functional disability. Although not significant at the .05 level, disease status and disease activity were also positively correlated with learned helplessness. Additionally, unemployed individuals were more likely to be helpless than employed individuals. Overall, the results suggest that learned helplessness is related to negative health indicators in the multiple sclerosis population. Nursing interventions to decrease or prevent learned helplessness may be appropriate in this population.

Using normalisation process theory to understand barriers and facilitators to implementing mindfulness-based stress reduction for people with multiple sclerosis.

PubMed

Simpson, Robert; Simpson, Sharon; Wood, Karen; Mercer, Stewart W; Mair, Frances S

2018-01-01

Objectives To study barriers and facilitators to implementation of mindfulness-based stress reduction for people with multiple sclerosis. Methods Qualitative interviews were used to explore barriers and facilitators to implementation of mindfulness-based stress reduction, including 33 people with multiple sclerosis, 6 multiple sclerosis clinicians and 2 course instructors. Normalisation process theory provided the underpinning conceptual framework. Data were analysed deductively using normalisation process theory constructs (coherence, cognitive participation, collective action and reflexive monitoring). Results Key barriers included mismatched stakeholder expectations, lack of knowledge about mindfulness-based stress reduction, high levels of comorbidity and disability and skepticism about embedding mindfulness-based stress reduction in routine multiple sclerosis care. Facilitators to implementation included introducing a pre-course orientation session; adaptations to mindfulness-based stress reduction to accommodate comorbidity and disability and participants suggested smaller, shorter classes, shortened practices, exclusion of mindful-walking and more time with peers. Post-mindfulness-based stress reduction booster sessions may be required, and objective and subjective reports of benefit would increase clinician confidence in mindfulness-based stress reduction. Discussion Multiple sclerosis patients and clinicians know little about mindfulness-based stress reduction. Mismatched expectations are a barrier to participation, as is rigid application of mindfulness-based stress reduction in the context of disability. Course adaptations in response to patient needs would facilitate uptake and utilisation. Rendering access to mindfulness-based stress reduction rapid and flexible could facilitate implementation. Embedded outcome assessment is desirable.

Diagnostic value of conventional visual evoked potentials applied to patients with multiple sclerosis.

PubMed

Balnytė, Renata; Ulozienė, Ingrida; Rastenytė, Daiva; Vaitkus, Antanas; Malcienė, Lina; Laučkaitė, Kristina

2011-01-01

The aim of this study was to determine the sensitivity and specificity of this classical technique employed at the Hospital of Lithuanian University of Health Sciences for the patients with multiple sclerosis and to assess its possible correlations with affected neurological systems. Pattern shift visual evoked potentials were recorded in 63 patients with multiple sclerosis, 17 (27%) of whom had a history of optic neuritis, and in 63 control patients with other neurological diseases. The latencies and amplitudes of P100 were measured. In total, 126 patients were referred to the inpatient department of neurology for differential diagnosis of demyelinating disorders between January and December of 2007. Abnormalities of visual evoked potentials were observed by 73% more frequently in patients with multiple sclerosis than in control patients (α=0.05, β<0.01). The combined monocular/interocular test showed a specificity of 90.5% and a sensitivity of 82.5%. The probability of an affection of the pyramidal system was 5 times greater (95% CI, 2.2-11.0; P<0.01) and the probability of the optic pathways involvement was 4.8 times greater (95% CI, 1.9-11.9; P<0.01) in patients with multiple sclerosis than in controls. Conventional visual evoked potentials must be reappraised in light of their diagnostic value in multiple sclerosis given their high diagnostic efficiency, relatively easy, short, and cheap implementation, and easy availability in everyday clinical practice.

Validity and reliability of the multidimensional assessment of fatigue scale in Iranian patients with relapsing-remitting subtype of multiple sclerosis.

PubMed

Behrangrad, Shabnam; Kordi Yoosefinejad, Amin

2018-03-01

The purpose of this study is to investigate the validity and reliability of the Persian version of the Multidimensional Assessment of Fatigue Scale (MAFS) in an Iranian population with multiple sclerosis. A self-reported survey on fatigue including the MAFS, Fatigue Impact Scale and demographic measures was completed by 130 patients with multiple sclerosis and 60 healthy persons sampled with a convenience method. Test-retest reliability and validity were evaluated 3 days apart. Construct validity of the MAFS was assessed with the Fatigue Impact Scale. The MAFS had high internal consistency (Cronbach's alpha >0.9) and 3-d test-retest reliability (intraclass correlation coefficient = 0.99). Correlation between the Fatigue Impact Scale and MAFS was high (r = 0.99). Correlation between MAFS scores and the Expanded Disability Status Scale was also strong (r = 0.85). Questionnaire items showed acceptable item-scale correlation (0.968-0.993). The Persian version of the MAFS appears to be a valid and reliable questionnaire. It is an appropriate short multidimensional instrument to assess fatigue in patients with multiple sclerosis in clinical practice and research. Implications for Rehabilitation The Persian version of Multidimensional Assessment of Fatigue is a valid and reliable instrument for the assessment and monitoring the fatigue in Persian-language patients with multiple sclerosis. It is very easy to administer and a time efficient scale in comparison to other instruments evaluating fatigue in patients with multiple sclerosis.

Pain and Cognition in Multiple Sclerosis.

PubMed

Scherder, R; Kant, N; Wolf, E; Pijnenburg, A C M; Scherder, E

2017-10-01

The goal of the present study was to examine the relationship between pain and cognition in patients with multiple sclerosis. Cross-sectional. Nursing home and personal environment of the investigators. Two groups of participants were included: 91 patients with multiple sclerosis and 80 matched control participants. The level of pain was measured by the following pain scales: Number of Words Chosen-Affective, Colored Analogue Scale for pain intensity and suffering from pain, and the Faces Pain Scale. Mood was tested by administering the Beck Depression Inventory and the Symptom Check List-90 anxiety and depression subscale. Global cognitive functioning was assessed by the Mini Mental State Examination. Memory and executive functions were assessed by several neuropsychological tests. Multiple sclerosis (MS) patients scored significantly lower than control participants on the majority of the neuropsychological tests. The MS patients experienced more pain compared with control participants, despite the fact that they were taking significantly more pain medication. No significant correlation was observed between cognition and pain in MS patients. Verbal working memory explained 10% of pain intensity (trend). Mood appeared to be a significant predictor of pain in patients with multiple sclerosis. The lack of a relationship between cognition and pain might be explained by the fact that, compared with control participants, patients with multiple sclerosis activate other non-pain-related areas to perform executive functions and memory tasks. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Circular RNA profiling reveals that circular RNAs from ANXA2 can be used as new biomarkers for multiple sclerosis.

PubMed

Iparraguirre, Leire; Muñoz-Culla, Maider; Prada-Luengo, Iñigo; Castillo-Triviño, Tamara; Olascoaga, Javier; Otaegui, David

2017-09-15

Multiple sclerosis is an autoimmune disease, with higher prevalence in women, in whom the immune system is dysregulated. This dysregulation has been shown to correlate with changes in transcriptome expression as well as in gene-expression regulators, such as non-coding RNAs (e.g. microRNAs). Indeed, some of these have been suggested as biomarkers for multiple sclerosis even though few biomarkers have reached the clinical practice. Recently, a novel family of non-coding RNAs, circular RNAs, has emerged as a new player in the complex network of gene-expression regulation. MicroRNA regulation function through a 'sponge system' and a RNA splicing regulation function have been proposed for the circular RNAs. This regulating role together with their high stability in biofluids makes them seemingly good candidates as biomarkers. Given the dysregulation of both protein-coding and non-coding transcriptome that have been reported in multiple sclerosis patients, we hypothesised that circular RNA expression may also be altered. Therefore, we carried out expression profiling of 13.617 circular RNAs in peripheral blood leucocytes from multiple sclerosis patients and healthy controls finding 406 differentially expressed (P-value < 0.05, Fold change > 1.5) and demonstrate after validation that, circ_0005402 and circ_0035560 are underexpressed in multiple sclerosis patients and could be used as biomarkers of the disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Multiple sclerosis in pregnancy: prevalence, sociodemographic features, and obstetrical outcomes.

PubMed

Fong, Alex; Chau, Cindy T; Quant, Cara; Duffy, Jennifer; Pan, Deyu; Ogunyemi, Dotun A

2018-02-01

We sought to describe the prevalence, sociodemographic features, and antenatal/peripartum outcomes of multiple sclerosis (MS) in pregnancy. A retrospective cohort study was performed using deliveries in California from 2001 to 2009. Cases of MS as well as other morbidities were identified via ICD-9-CM code. Logistic regression was performed to adjust for potential confounders. About 1185 out of 4,424,049 deliveries were complicated by MS. MS prevalence increased with maternal age, with Caucasians comprising a higher proportion of MS subjects. MS subjects were older and more likely to have private insurance. Women with MS were more likely to have preexisting medical conditions such as asthma, chronic hypertension, thyroid disease, or cardiac disease. However, no significant antepartum and peripartum morbidities were found to be increased in patients with MS. Urinary tract infection, cesarean delivery, and induction of labor were slightly increased in MS patients. MS is a rare condition which is more likely to affect older Caucasian women of higher socioeconomic status and is associated with several preexisting medical conditions. MS, however, does not appear to pose significant increases in adverse pregnancy outcome. This suggests that pregnant patients with MS may likely experience an uneventful pregnancy.

Personality as a predictor of coping efforts in patients with multiple sclerosis.

PubMed

Rätsep, T; Kallasmaa, T; Pulver, A; Gross-Paju, K

2000-12-01

The aim of the study was to explore personality traits as predictors of coping with disease-related distress in patients with multiple sclerosis (MS). All patients with clinically definite MS in a city with a population of approximately 100000 were asked to complete the NEO Personality Inventory and a multidimensional coping inventory (COPE). There was an 83% response rate yielding 49 patients for the study population and 49 controls, matched for age, gender and educational level to the MS-patients, were used as comparison. Only Neuroticism correlated significantly with emotion-focused coping in both groups. Extraversion and Openness to Experience were linked to task-oriented coping strategies in normal controls but not in the MS-group. Agreeableness was associated with avoidance-oriented coping strategies only in the MS-group. Thus, the relation of certain personality characteristics to the choice of strategies for coping with the disease-related distress appear to differ from coping with stressful problems in everyday life. As dispositional characteristics may interfere with adaptive coping responses, analysis of personality traits and coping strategies could contribute while attempting to relieve the consequences of chronic disease on everyday life.

Cerebrospinal Fluid B Cells Correlate with Early Brain Inflammation in Multiple Sclerosis

PubMed Central

Kuenz, Bettina; Lutterotti, Andreas; Ehling, Rainer; Gneiss, Claudia; Haemmerle, Monika; Rainer, Carolyn; Deisenhammer, Florian; Schocke, Michael; Berger, Thomas; Reindl, Markus

2008-01-01

Background There is accumulating evidence from immunological, pathological and therapeutic studies that B cells are key components in the pathophysiology of multiple sclerosis (MS). Methodology/Principal Findings In this prospective study we have for the first time investigated the differences in the inflammatory response between relapsing and progressive MS by comparing cerebrospinal fluid (CSF) cell profiles from patients at the onset of the disease (clinically isolated syndrome, CIS), relapsing-remitting (RR) and chronic progressive (CP) MS by flow cytometry. As controls we have used patients with other neurological diseases. We have found a statistically significant accumulation of CSF mature B cells (CD19+CD138−) and plasma blasts (CD19+CD138+) in CIS and RRMS. Both B cell populations were, however, not significantly increased in CPMS. Further, this accumulation of B cells correlated with acute brain inflammation measured by magnetic resonance imaging and with inflammatory CSF parameters such as the number of CSF leukocytes, intrathecal immunoglobulin M and G synthesis and intrathecal production of matrix metalloproteinase (MMP)-9 and the B cell chemokine CxCL-13. Conclusions Our data support an important role of CSF B cells in acute brain inflammation in CIS and RRMS. PMID:18596942

Recent Advances in Monoclonal Antibody Therapies for Multiple Sclerosis.

PubMed

Wootla, Bharath; Watzlawik, Jens O; Stavropoulos, Nikolaos; Wittenberg, Nathan J; Dasari, Harika; Abdelrahim, Murtada A; Henley, John R; Oh, Sang-Hyun; Warrington, Arthur E; Rodriguez, Moses

2016-06-01

Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating disease of the CNS and results in neurological disability. Existing immunomodulatory and immunosuppressive approaches lower the number of relapses but do not cure or reverse existing deficits nor improve long-term disability in MS patients. Monogenic antibodies were described as treatment options for MS, however the immunogenicity of mouse antibodies hampered the efficacy of potential therapeutics in humans. Availability of improved antibody production technologies resulted in a paradigm shift in MS treatment strategies. In this review, an overview of immunotherapies for MS that use conventional monoclonal antibodies reactive to immune system and their properties and mechanisms of action will be discussed, including recent advances in MS therapeutics and highlight natural autoantibodies (NAbs) that directly target CNS cells. Recent challenges for MS therapy are the identification of relevant molecular and cellular targets, time frame of treatment, and antibody toxicity profiles to identify safe treatment options for MS patients. The application of monoclonal antibody therapies with better biological efficacy associated with minimum side effects possesses huge clinical potential. Advances in monoclonal antibody technologies that directly target cells of nervous system may promote the CNS regeneration field from bench to bedside.

[Cormorbidity in multiple sclerosis and its therapeutic approach].

PubMed

Estruch, Bonaventura Casanova

2014-12-01

Multiple sclerosis (MS) is a long-term chronic disease, in which intercurrent processes develop three times more frequently in affected individuals than in persons without MS. Knowledge of the comorbidity of MS, its definition and measurement (Charlson index) improves patient management. Acting on comorbid conditions delays the progression of disability, which is intimately linked to the number of concurrent processes and with health states and habits. Moreover, the presence of comorbidities delays the diagnosis of MS, which in turn delays the start of treatment. The main comorbidity found in MS includes other autoimmune diseases (thyroiditis, systemic lupus erythematosus, or pemphigus) but can also include general diseases, such as asthma or osteomuscular alterations, and, in particular, psychiatric disturbances. All these alterations should be evaluated with multidimensional scales (Disability Expectancy Table, DET), which allow more accurate determination of the patient's real clinical course and quality of life. These scales also allow identification of how MS, concurrent and intercurrent processes occurring during the clinical course, and the treatment provided affect patients with MS. An overall approach to patients' health status helps to improve quality of life. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

The stress-buffering effects of hope on adjustment to multiple sclerosis.

PubMed

Madan, Sindia; Pakenham, Kenneth I

2014-12-01

Hope is an important resource for coping with chronic illness; however, the role of hope in adjusting to multiple sclerosis (MS) has been neglected, and the mechanisms by which hope exerts beneficial impacts are not well understood. This study aims to examine the direct and stress-moderating effects of dispositional hope and its components (agency and pathways) on adjustment to MS. A total of 296 people with MS completed questionnaires at time 1 at 12 months later and time 2. Focal predictors were stress, hope, agency and pathways, and the adjustment outcomes were anxiety, depression, positive affect, positive states of mind and life satisfaction. Results of regression analyses showed that as predicted, greater hope was associated with better adjustment after controlling for the effects of time 1 adjustment and relevant demographics and illness variables. However, these direct effects of hope were subsumed by stress-buffering effects. Regarding the hope components, the beneficial impacts of agency emerged via a direct effects mechanism, whereas the effects of pathways were evidenced via a moderating mechanism. Findings highlight hope as an important protective coping resource for coping with MS and accentuate the roles of both agency and pathways thinking and their different modes of influence in this process.

Improving quality of life in multiple sclerosis: an unmet need.

PubMed

Zwibel, Howard L; Smrtka, Jennifer

2011-05-01

Multiple sclerosis (MS) affects approximately 400,000 people in the United States and 2.1 million people worldwide. It is the most common chronic, non-traumatic neurological disorder afflicting young people during their peak productive ages. MS can diminish quality of life (QOL) by interfering with the ability to work, pursue leisure activities, and carry on usual life roles. Symptoms that affect QOL may include impaired mobility, fatigue, depression, pain, spasticity, cognitive impairment, sexual dysfunction, bowel and bladder dysfunction, vision and hearing problems, seizures, and sDwallowing and breathing difficulties. Direct medical costs of MS in the United States are estimated in excess of $10 billion per year. Indirect costs of MS include costs of reduced employment or unemployment, assistive equipment, disability related home modifications, and paid and unpaid personal care. Although direct medical costs predominate in the earlier stages of MS, indirect costs of productivity loss are responsible for higher costs later. Disease-modifying therapies (DMTs) lessen symptoms, reduce relapses, and delay disability progression. Unfortunately, many DMTs might produce only modest improvements in QOL. Although symptom-specific therapies do not delay disease progression, they may delay unemployment and dependency, thereby reducing indirect costs.

Recent Advances in Monoclonal Antibody Therapies for Multiple Sclerosis

PubMed Central

Stavropoulos, Nikolaos; Wittenberg, Nathan J.; Dasari, Harika; Abdelrahim, Murtada A.; Henley, John R.; Oh, Sang-Hyun; Warrington, Arthur E.; Rodriguez, Moses

2016-01-01

Introduction Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating disease of the CNS and results in neurological disability. Existing immunomodulatory and immunosuppressive approaches lower the number of relapses but do not cure or reverse existing deficits nor improve long-term disability in MS patients. Areas Covered Monogenic antibodies were described as treatment options for MS, however the immunogenicity of mouse antibodies hampered the efficacy of potential therapeutics in humans. Availability of improved antibody production technologies resulted in a paradigm shift in MS treatment strategies. In this review, an overview of immunotherapies for MS that use conventional monoclonal antibodies reactive to immune system and their properties and mechanisms of action will be discussed, including recent advances in MS therapeutics and highlight natural autoantibodies (NAbs) that directly target CNS cells. Expert Opinion Recent challenges for MS therapy are the identification of relevant molecular and cellular targets, time frame of treatment, and antibody toxicity profiles to identify safe treatment options for MS patients. The application of monoclonal antibody therapies with better biological efficacy associated with minimum side effects possesses huge clinical potential. Advances in monoclonal antibody technologies that directly target cells of nervous system may promote the CNS regeneration field from bench to bedside. PMID:26914737

Overview and diagnosis of multiple sclerosis.

PubMed

Hunter, Samuel F

2016-06-01

Multiple sclerosis (MS), a chronic inflammatory disease of unknown etiology, involves an immunemediated attack of the central nervous system (CNS) that produces demyelination and axonal/neuronal damage, resulting in characteristic multifocal lesions apparent on magnetic resonance imaging and a variety of neurologic manifestations. The disease pathology is characterized by multifocal lesions within the CNS, in both the white matter and gray matter, with perivenular inflammatory cell infiltrates, demyelination, axonal transection, neuronal degeneration, and gliosis. MS pathogenesis is complex, as it involves both T- and B-cell mechanisms and is heterogeneous in presentation. Relatively recently, the historical 4 core clinical categories of MS were revised in an effort to improve characterization of the clinical course, better identify where a given patient is positioned in the disease spectrum, and to guide clinical studies. In young and middle-aged adults, MS is one of the most common contributors to neurologic disability, and it exerts detrimental effects on a patient's productivity and health-related quality of life. Typically, patients with MS have a long life span, although healthcare utilization increases over time. As a consequence, the disease places a substantial burden on patients and their caregivers/families, as well as employers, the healthcare system, and society.

Multiple Sclerosis.

PubMed

Yamout, Bassem I; Alroughani, Raed

2018-04-01

Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease of autoimmune etiology, mediated by activated T cells with evolving evidence of a significant contribution from B cells and cells of the innate immune system. The disease is thought to be due to a complex interaction between different genetic and environmental factors. The prevalence of MS is rising all over the world, due on one hand to earlier diagnosis and prolonged survival, and on the other to a true increase in incidence of the disease. The diagnosis of MS remains clinical despite recent advances in diagnostics and relies on demonstrating dissemination in space and time while excluding alternative diagnoses. The Mc Donald diagnostic criteria, with their recent 2017 revision, are currently widely accepted in the MS community. Although no cure is yet available, many disease-modifying therapies (DMTs) have shown different levels of efficacy in preventing relapses, accumulation of lesions on magnetic resonance imaging (MRI), and disability progression. Current treatment strategies include gradual escalation based on clinical and radiological criteria that determine treatment response, or initial induction with high efficacy DMTs especially in patients with an early aggressive course. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Epstein-Barr virus and multiple sclerosis.

PubMed

Pohl, Daniela

2009-11-15

Epstein-Barr virus (EBV) is a human DNA herpesvirus infecting more than 90% of the world's population. EBV is the etiological agent of infectious mononucleosis (Pfeiffer's disease). Furthermore, diverse malignancies such as Burkitt and Hodgkin lymphoma have been associated with EBV. More recently, a possible role for EBV has been suggested in chronic inflammatory/autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus as well as in multiple sclerosis (MS). MS is currently regarded as a disease with multifactorial etiology, EBV being one possible factor in MS manifestation: Infectious mononucleosis has been shown to increase the risk of developing MS later in life. EBV seroprevalence rates are higher in MS as compared to controls, in adult as well as in pediatric MS patients. Moreover, EBV antibody titres and EBV specific T-cells are increased in MS patients as compared to healthy individuals. Recently, CNS B-cells of MS patients have been reported to harbour EBV. However, there is still controversy whether EBV could be a causative agent as opposed to an innocent bystander in the pathogenesis of MS. This review summarizes current knowledge on the association of EBV and MS including a critical discussion of equivocal findings.

Effect of optic neuritis on progressive axonal damage in multiple sclerosis patients.

PubMed

Garcia-Martin, E; Pueyo, V; Ara, J R; Almarcegui, C; Martin, J; Pablo, L; Dolz, I; Sancho, E; Fernandez, F J

2011-07-01

The objective of this research was to study the effect of optic neuritis (ON) on axonal damage in multiple sclerosis (MS) patients. Specifically, we compared changes over 2 years in the retinal nerve fibre layer (RNFL) between affected and contralateral eyes in MS patients with a prior history of ON. Thirty-four patients with one unilateral definitive episode of ON were included and underwent a complete ophthalmic examination, optical coherence tomography (OCT), scanning laser polarimetry, visual evoked potentials (VEP) and pattern electroretinogram (pERG). All patients were re-evaluated at 12 and 24 months. Parameters were compared between ON-affected and contralateral eyes in an initial exploration and over the course of the follow-up. Correlations between parameter changes were analysed. RNFL thickness and functional parameters showed more affection in ON eyes (p ≤ 0.05), but changes in measurements during the study were similar between both groups of eyes. Progressive axonal loss can be detected in the optic nerve, but ON is not a risk factor for increased chronic damage in MS patients without ophthalmic relapses. Loss of the RNFL is caused by progressive degeneration associated with the disease.

Treatment of a multiple sclerosis animal model by a novel nanodrop formulation of a natural antioxidant

PubMed Central

Binyamin, Orli; Larush, Liraz; Frid, Kati; Keller, Guy; Friedman-Levi, Yael; Ovadia, Haim; Abramsky, Oded; Magdassi, Shlomo; Gabizon, Ruth

2015-01-01

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and is associated with demyelination, neurodegeneration, and sensitivity to oxidative stress. In this work, we administered a nanodroplet formulation of pomegranate seed oil (PSO), denominated Nano-PSO, to mice induced for experimental autoimmune encephalomyelitis (EAE), an established model of MS. PSO comprises high levels of punicic acid, a unique polyunsaturated fatty acid considered as one of the strongest natural antioxidants. We show here that while EAE-induced mice treated with natural PSO presented some reduction in disease burden, this beneficial effect increased significantly when EAE mice were treated with Nano-PSO of specific size nanodroplets at much lower concentrations of the oil. Pathological examinations revealed that Nano-PSO administration dramatically reduced demyelination and oxidation of lipids in the brains of the affected animals, which are hallmarks of this severe neurological disease. We propose that novel formulations of natural antioxidants such as Nano-PSO may be considered for the treatment of patients suffering from demyelinating diseases. On the mechanistic side, our results demonstrate that lipid oxidation may be a seminal feature in both demyelination and neurodegeneration. PMID:26648720

Aquatherapy for neurodegenerative disorders.

PubMed

Plecash, Alyson R; Leavitt, Blair R

2014-01-01

Aquatherapy is used for rehabilitation and exercise; water provides a challenging, yet safe exercise environment for many special populations. We have reviewed the use of aquatherapy programs in four neurodegenerative disorders: Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. Results support the use of aquatherapy in Parkinson's disease and multiple sclerosis, however further evidence is required to make specific recommendations in all of the aforementioned disorders.

[Systematic review of safeness and therapeutic efficacy of cannabis in patients with multiple sclerosis, neuropathic pain, and in oncological patients treated with chemotherapy].

PubMed

Amato, Laura; Minozzi, Silvia; Mitrova, Zuzana; Parmelli, Elena; Saulle, Rosella; Cruciani, Fabio; Vecchi, Simona; Davoli, Marina

2017-01-01

medical cannabis refers to the use of cannabis or cannabinoids as medical therapy to treat disease or alleviate symptoms. In the United States, 23 states and Washington DC (May 2015) have introduced laws to permit the medical use of cannabis. Within the European Union, medicinal cannabis laws and praxis vary wildly between Countries. to provide evidence for benefits and harms of cannabis (including extracts and tinctures) treatment for adults in the following indications: control of spasticity and pain in patients with multiple sclerosis; control of pain in patients with chronic neuropathic pain; control of nausea and vomiting in adults with cancer receiving chemotherapy. we searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE from inception to September 2016. We also searched for on-going studies via ClinicalTrials.gov and the World Health Organization and International Clinical Trials Registry Platform (ICTRP) search portal. All searches included also non-English language literature. All relevant randomized controlled trials (RCTs) evaluating the safety and efficacy of cannabis (including extracts and tinctures) compared with placebo or other pharmacological agents were included. Three authors independently evaluated the titles and abstracts of studies identified in the literature searches for their eligibility. For studies considered eligible, we retrieved full texts. Three investigators independently extracted data. For the assessment of the quality of evidence, we used the standard methodological procedures recommended by Cochrane and GRADE working Group. 41 trials (4,550 participants) were included; 15 studies considered efficacy and safety of cannabis for patients with multiple sclerosis, 12 for patients with chronic pain, and 14 for patients with cancer receiving chemotherapy. The included studies were published between 1975 and 2015, and the majority of them were conducted in Europe. We judged almost 50% of these studies to be at low risk of bias. The large majority (80%) of the comparisons were with placebo; only 8 studies included patients with cancer receiving chemotherapy comparing cannabis with other antiemetic drugs. Concerning the efficacy of cannabis (compared with placebo) in patients with multiple sclerosis, confidence in the estimate was high in favour of cannabis for spasticity (numerical rating scale and visual analogue scale, but not the Ashworth scale) and pain. For chronic and neuropathic pain (compared with placebo), there was evidence of a small effect; however, confidence in the estimate is low and these results could not be considered conclusive. There is uncertainty whether cannabis, including extracts and tinctures, compared with placebo or other antiemetic drugs reduces nausea and vomiting in patients with cancer requiring chemotherapy, although the confidence in the estimate of the effect was low or very low. In the included studies, many adverse events were reported and none of the studies assessed the development of abuse or dependence. there is incomplete evidence of the efficacy and safety of medical use of cannabis in the clinical contexts considered in this review. Furthermore, for many of the outcomes considered, the confidence in the estimate of the effect was again low or very low. To give conclusive answers to the efficacy and safety of cannabis used for medical purposes in the clinical contexts considered, further studies are needed, with higher quality, larger sample sizes, and possibly using the same diagnostic tools for evaluating outcomes of interest.

Inhibiting poly(ADP-ribose) polymerase: a potential therapy against oligodendrocyte death

PubMed Central

Veto, Sara; Acs, Peter; Bauer, Jan; Lassmann, Hans; Berente, Zoltan; Setalo, Gyorgy; Borgulya, Gabor; Sumegi, Balazs; Komoly, Samuel; Gallyas, Ferenc; Illes, Zsolt

2010-01-01

Oligodendrocyte loss and demyelination are major pathological hallmarks of multiple sclerosis. In pattern III lesions, inflammation is minor in the early stages, and oligodendrocyte apoptosis prevails, which appears to be mediated at least in part through mitochondrial injury. Here, we demonstrate poly(ADP-ribose) polymerase activation and apoptosis inducing factor nuclear translocation within apoptotic oligodendrocytes in such multiple sclerosis lesions. The same morphological and molecular pathology was observed in an experimental model of primary demyelination, induced by the mitochondrial toxin cuprizone. Inhibition of poly(ADP-ribose) polymerase in this model attenuated oligodendrocyte depletion and decreased demyelination. Poly(ADP-ribose) polymerase inhibition suppressed c-Jun N-terminal kinase and p38 mitogen-activated protein kinase phosphorylation, increased the activation of the cytoprotective phosphatidylinositol-3 kinase-Akt pathway and prevented caspase-independent apoptosis inducing factor-mediated apoptosis. Our data indicate that poly(ADP-ribose) polymerase activation plays a crucial role in the pathogenesis of pattern III multiple sclerosis lesions. Since poly(ADP-ribose) polymerase inhibition was also effective in the inflammatory model of multiple sclerosis, it may target all subtypes of multiple sclerosis, either by preventing oligodendrocyte death or attenuating inflammation. PMID:20157013

Effects of physiotherapy interventions on balance in multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Paltamaa, Jaana; Sjögren, Tuulikki; Peurala, Sinikka H; Heinonen, Ari

2012-10-01

To determine the effects of physiotherapy interventions on balance in people with multiple sclerosis. A systematic literature search was conducted in Medline, Cinahl, Embase, PEDro, both electronically and by manual search up to March 2011. Randomized controlled trials of physiotherapy interventions in people with multiple sclerosis, with an outcome measure linked to the International Classification of Functioning, Disability and Health (ICF) category of "Changing and maintaining body position", were included. The quality of studies was determined by the van Tulder criteria. Meta-analyses were performed in subgroups according to the intervention. After screening 233 full-text papers, 11 studies were included in a qualitative analysis and 7 in a meta-analysis. The methodological quality of the studies ranged from poor to moderate. Low evidence was found for the efficacy of specific balance exercises, physical therapy based on an individualized problem-solving approach, and resistance and aerobic exercises on improving balance among ambulatory people with multiple sclerosis. These findings indicate small, but significant, effects of physiotherapy on balance in people with multiple sclerosis who have a mild to moderate level of disability. However, evidence for severely disabled people is lacking, and further research is needed.

Effect of exercise training on walking mobility in multiple sclerosis: a meta-analysis.

PubMed

Snook, Erin M; Motl, Robert W

2009-02-01

The study used meta-analytic procedures to examine the overall effect of exercise training interventions on walking mobility among individuals with multiple sclerosis. A search was conducted for published exercise training studies from 1960 to November 2007 using MEDLINE, PsychINFO, CINAHL, and Current Contents Plus. Studies were selected if they measured walking mobility, using instruments identified as acceptable walking mobility constructs and outcome measures for individuals with neurologic disorders, before and after an intervention that included exercise training. Forty-two published articles were located and reviewed, and 22 provided enough data to compute effect sizes expressed as Cohen's d. Sixty-six effect sizes were retrieved from the 22 publications with 600 multiple sclerosis participants and yielded a weighted mean effect size of g = 0.19 (95% confidence interval, 0.09-0.28). There were larger effects associated with supervised exercise training ( g = 0.32), exercise programs that were less than 3 months in duration (g = 0.28), and mixed samples of relapsing-remitting and progressive multiple sclerosis (g = 0.52). The cumulative evidence supports that exercise training is associated with a small improvement in walking mobility among individuals with multiple sclerosis.

Cognitive dysfunction in multiple sclerosis: a review of recent developments.

PubMed

Bobholz, Julie A; Rao, Stephen M

2003-06-01

Nearly half of all patients diagnosed with multiple sclerosis will develop cognitive dysfunction, a symptom associated with significant decline in activities of daily living. The purpose of this review is to discuss recent literature investigating issues related to cognitive dysfunction in multiple sclerosis. Recent studies, examined in this review, have provided increased understanding regarding specific cognitive processes affected in multiple sclerosis, as well as a characterization of its natural history. Studies have also continued to emphasize the extent to which cognitive deficits in the condition are associated with decline in daily living skills. Recent concerns regarding driving performance have been documented among cognitively impaired individuals. Studies have also examined correlates of cognitive dysfunction, with particular emphasis on neuroimaging techniques reflecting disease activity or lesion burden. With increased understanding of neurobiological correlates of cognitive deficits, investigators have begun to examine potential treatments for managing cognitive dysfunction. This area of research has suggested that disease modifying medications can have an impact on magnetic resonance imaging disease activity by altering the cerebral demyelinating process resulting in a slower decline in cognitive functions over time and improved activities of daily living for patients with multiple sclerosis.

Disability and Fatigue Can Be Objectively Measured in Multiple Sclerosis

PubMed Central

Motta, Caterina; Palermo, Eduardo; Studer, Valeria; Germanotta, Marco; Germani, Giorgio; Centonze, Diego; Cappa, Paolo

2016-01-01

Background The available clinical outcome measures of disability in multiple sclerosis are not adequately responsive or sensitive. Objective To investigate the feasibility of inertial sensor-based gait analysis in multiple sclerosis. Methods A cross-sectional study of 80 multiple sclerosis patients and 50 healthy controls was performed. Lower-limb kinematics was evaluated by using a commercially available magnetic inertial measurement unit system. Mean and standard deviation of range of motion (mROM, sROM) for each joint of lower limbs were calculated in one minute walking test. A motor performance index (E) defined as the sum of sROMs was proposed. Results We established two novel observer-independent measures of disability. Hip mROM was extremely sensitive in measuring lower limb motor impairment, being correlated with muscle strength and also altered in patients without clinically detectable disability. On the other hand, E index discriminated patients according to disability, being altered only in patients with moderate and severe disability, regardless of walking speed. It was strongly correlated with fatigue and patient-perceived health status. Conclusions Inertial sensor-based gait analysis is feasible and can detect clinical and subclinical disability in multiple sclerosis. PMID:26863109

Coping mediates the relationship between sense of coherence and mental quality of life in patients with chronic illness: a cross-sectional study.

PubMed

Kristofferzon, Marja-Leena; Engström, Maria; Nilsson, Annika

2018-07-01

The aim of the present study was to investigate relationships between sense of coherence, emotion-focused coping, problem-focused coping, coping efficiency, and mental quality of life (QoL) in patients with chronic illness. A model based on Lazarus' and Folkman's stress and coping theory tested the specific hypothesis: Sense of coherence has a direct and indirect effect on mental QoL mediated by emotion-focused coping, problem-focused coping, and coping efficiency in serial adjusted for age, gender, educational level, comorbidity, and economic status. The study used a cross-sectional and correlational design. Patients (n = 292) with chronic diseases (chronic heart failure, end-stage renal disease, multiple sclerosis, stroke, and Parkinson) completed three questionnaires and provided background data. Data were collected in 2012, and a serial multiple mediator model was tested using PROCESS macro for SPSS. The test of the conceptual model confirmed the hypothesis. There was a significant direct and indirect effect of sense of coherence on mental QoL through the three mediators. The model explained 39% of the variance in mental QoL. Self-perceived effective coping strategies are the most important mediating factors between sense of coherence and QoL in patients with chronic illness, which supports Lazarus' and Folkman's stress and coping theory.

Schilder's Disease

MedlinePlus

... Information from the National Library of Medicine’s MedlinePlus Multiple Sclerosis × What research is being done? The NINDS supports ... Information from the National Library of Medicine’s MedlinePlus Multiple Sclerosis See More About Research The NINDS supports and ...

Shaking Out Clues to Autoimmune Disease

MedlinePlus

... include type 1 diabetes, inflammatory bowel diseases and multiple sclerosis. Researchers have found many genetic variants that affect ... they examined a mouse disease that resembles human multiple sclerosis. Mice lacking SGK1 had less severe symptoms and ...

Discussions about treatment restrictions in chronic neurologic diseases: a structured review.

PubMed

Seeber, Antje A; Hijdra, Albert; Vermeulen, Marinus; Willems, Dick L

2012-02-21

Many incurable neurologic diseases have predictable complications during their course or at their end stage. Timely discussions of potential treatment restrictions may improve the quality of treatment decisions toward the end of life. What is known about the actual practice of these discussions? We performed a literature search in MEDLINE, EMBASE, and CINAHL for empirical studies about discussions and decisions to restrict treatment in the course of 6 conditions: motor neuron disease (amyotrophic lateral sclerosis [ALS]), primary malignant brain tumors, multiple sclerosis, stroke, Parkinson disease, and dementia (Alzheimer disease). In 10 of 43 studies, the actual practice of decision-making was studied; in the remaining 33, caregivers were interviewed about this practice. Three scenarios were described: 1) acute devastating disease (severe stroke); 2) stable severe neurologic deficit with complications (poststroke brain damage); and 3) chronic progressive disease with complications (dementia and ALS). We found no studies concerning the other conditions. In all 3 scenarios, discussions and decisions seemed to be mostly triggered by the occurrence of life-threatening situations, either caused by the disease itself (1), or complications (2 and 3, including many patients with ALS). Some ALS studies showed that timely discussion of treatment options improved end-of-life decision-making. The actual practice of discussions about treatment restrictions in chronic neurologic disease has hardly been studied. The currently available empirical data suggest that discussions are mainly triggered by life-threatening situations, whereas anticipation of such situations may be beneficial for patients and their families.

Creatine Enhances Mitochondrial-Mediated Oligodendrocyte Survival After Demyelinating Injury.

PubMed

Chamberlain, Kelly A; Chapey, Kristen S; Nanescu, Sonia E; Huang, Jeffrey K

2017-02-08

Chronic oligodendrocyte loss, which occurs in the demyelinating disorder multiple sclerosis (MS), contributes to axonal dysfunction and neurodegeneration. Current therapies are able to reduce MS severity, but do not prevent transition into the progressive phase of the disease, which is characterized by chronic neurodegeneration. Therefore, pharmacological compounds that promote oligodendrocyte survival could be beneficial for neuroprotection in MS. Here, we investigated the role of creatine, an organic acid involved in adenosine triphosphate (ATP) buffering, in oligodendrocyte function. We found that creatine increased mitochondrial ATP production directly in oligodendrocyte lineage cell cultures and exerted robust protection on oligodendrocytes by preventing cell death in both naive and lipopolysaccharide-treated mixed glia. Moreover, lysolecithin-mediated demyelination in mice deficient in the creatine-synthesizing enzyme guanidinoacetate-methyltransferase ( Gamt ) did not affect oligodendrocyte precursor cell recruitment, but resulted in exacerbated apoptosis of regenerated oligodendrocytes in central nervous system (CNS) lesions. Remarkably, creatine administration into Gamt -deficient and wild-type mice with demyelinating injury reduced oligodendrocyte apoptosis, thereby increasing oligodendrocyte density and myelin basic protein staining in CNS lesions. We found that creatine did not affect the recruitment of macrophages/microglia into lesions, suggesting that creatine affects oligodendrocyte survival independently of inflammation. Together, our results demonstrate a novel function for creatine in promoting oligodendrocyte viability during CNS remyelination. SIGNIFICANCE STATEMENT We report that creatine enhances oligodendrocyte mitochondrial function and protects against caspase-dependent oligodendrocyte apoptosis during CNS remyelination. This work has important implications for the development of therapeutic targets for diseases characterized by oligodendrocyte death, including multiple sclerosis. Copyright © 2017 Chamberlain et al.

A bidirectional association between the gut microbiota and CNS disease in a biphasic murine model of multiple sclerosis.

PubMed

Colpitts, Sara L; Kasper, Eli J; Keever, Abigail; Liljenberg, Caleb; Kirby, Trevor; Magori, Krisztian; Kasper, Lloyd H; Ochoa-Repáraz, Javier

2017-11-02

The gut microbiome plays an important role in the development of inflammatory disease as shown using experimental models of central nervous system (CNS) demyelination. Gut microbes influence the response of regulatory immune cell populations in the gut-associated lymphoid tissue (GALT), which drive protection in acute and chronic experimental autoimmune encephalomyelitis (EAE). Recent observations suggest that communication between the host and the gut microbiome is bidirectional. We hypothesized that the gut microbiota differs between the acute inflammatory and chronic progressive stages of a murine model of secondary-progressive multiple sclerosis (SP-MS). This non-obese diabetic (NOD) model of EAE develops a biphasic pattern of disease that more closely resembles the human condition when transitioning from relapsing-remitting (RR)-MS to SP-MS. We compared the gut microbiome of NOD mice with either mild or severe disease to that of non-immunized control mice. We found that the mice which developed a severe secondary form of EAE harbored a dysbiotic gut microbiome when compared with the healthy control mice. Furthermore, we evaluated whether treatment with a cocktail of broad-spectrum antibiotics would modify the outcome of the progressive stage of EAE in the NOD model. Our results indicated reduced mortality and clinical disease severity in mice treated with antibiotics compared with untreated mice. Our findings support the hypothesis that there are reciprocal effects between experimental CNS inflammatory demyelination and modification of the microbiome providing a foundation for the establishment of early therapeutic interventions targeting the gut microbiome that could potentially limit disease progression.

Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison.

PubMed

Ramos, Sandra; Brenu, Ekua; Broadley, Simon; Kwiatek, Richard; Ng, Jennifer; Nguyen, Thao; Freeman, Susan; Staines, Donald; Marshall-Gradisnik, Sonya

2016-12-01

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), and Multiple Sclerosis (MS) may share some similarities in relation to reduced NK cell activity. It is likely that other cells such as regulatory T (Tregs), invariant Natural Killer T (iNKT) and gamma delta T (γδ T) cells may also be dysregulated in CFS/ME and MS. To evaluate and compare specific immune regulatory cells of patients with CFS/ME, patients with MS and healthy controls. Sixty three volunteers were included in this study: 24 were CFS/ME patients, 11 were MS patients and 27 were healthy controls. Blood samples were obtained from all participants for flow cytometry analysis of iNKT cells, Tregs and γδ T cell phenotypes. We observed a significant increase in Tregs in the CFS/ME group (p≤0.05) compared to the healthy control group. Total γδ and γδ2 T cells were significantly reduced in MS patients in comparison with the healthy control group. Conversely, CD4+iNKT percentage of iNKT, was significantly increased in the CFS/ME group compared with healthy controls and the double-negative iNKT percentage of iNKT significantly decreased compared with the healthy control group. This study has not identified any immunological disturbances that are common in both MS and CFS/ME patients. However, the differential expression of cell types between the conditions investigated suggests different pathways of disease. These differences need to be explored in further studies.

Multiple sclerosis with predominant, severe cognitive impairment

PubMed Central

Staff, Nathan P.; Lucchinetti, Claudia F.; Keegan, B. Mark

2009-01-01

Objective To describe the characteristics of multiple sclerosis (MS) presenting with severe cognitive impairment as its primary disabling manifestation. Design Retrospective case series. Setting Tertiary referral center. Patients Patients were identified through the Mayo Clinic data retrieval system (1996–2008) with definite MS (McDonald criteria) and severe cognitive impairment as their primary neurological symptom without accompanying significant MS-related impairment or alternative diagnosis for cognitive dysfunction. Twenty-three patients meeting inclusion criteria were compared regarding demographics, clinical course and radiological features. Main Outcome Measures Demographic, clinical, and radiological characteristics of the disease. Results Twelve patients were men. The median age of the first clinical symptom suggestive of CNS demyelination was 33 years, and severe MS-related cognitive impairment developed at a median of 39 years. Cognitive impairment could be dichotomized as subacute fulminant (n=9) or chronic progressive (n=14) in presentation, which corresponded to subsequent relapsing or progressive MS courses. Study patients commonly exhibited psychiatric (65%), mild cerebellar (57%) and cortical symptoms and signs (e.g. seizure, aphasia, apraxia) (39%). Fourteen of 21 (67%), where documented, smoked cigarettes. Brain MRI demonstrated diffuse cerebral atrophy in 16 and gadolinium enhancing lesions in 11. Asymptomatic spinal cord MRI lesions were present in 12 of 16 patients (75%). Immunomodulatory therapies were generally ineffective in improving these patients. Conclusions We describe patients with MS whose clinical phenotype is characterized by severe cognitive dysfunction and prominent cortical and psychiatric signs presenting as a subacute fulminant or chronic progressive clinical course. Cigarette smokers may be over represented in this phenotype. PMID:19752304

Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis

PubMed Central

Sellebjerg, Finn; Cadavid, Diego; Steiner, Deborah; Villar, Luisa Maria; Reynolds, Richard; Mikol, Daniel

2016-01-01

Multiple sclerosis (MS) is a common and chronic central nervous system (CNS) demyelinating disease and a leading cause of permanent disability. Patients most often present with a relapsing–remitting disease course, typically progressing over time to a phase of relentless advancement in secondary progressive MS (SPMS), for which approved disease-modifying therapies are limited. In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS. In both forms of MS, active brain-tissue injury is associated with inflammation; but in SPMS, the inflammatory response occurs at least partly behind the blood–brain barrier and is followed by a cascade of events, including persistent microglial activation that may lead to chronic demyelination and neurodegeneration associated with irreversible disability. In patients with relapsing forms of MS, natalizumab therapy is known to significantly reduce intrathecal inflammatory responses which results in reductions in brain lesions and brain atrophy as well as beneficial effects on clinical measures, such as reduced frequency and severity of relapse and reduced accumulation of disability. Natalizumab treatment also reduces levels of cerebrospinal fluid chemokines and other biomarkers of intrathecal inflammation, axonal damage and demyelination, and has demonstrated the ability to reduce innate immune activation and intrathecal immunoglobulin synthesis in patients with MS. The efficacy of natalizumab therapy in SPMS is currently being investigated in a randomized, double-blind, placebo-controlled trial. PMID:26788129

Evolutionary medicine and bone loss in chronic inflammatory diseases--A theory of inflammation-related osteopenia.

PubMed

Straub, Rainer H; Cutolo, Maurizio; Pacifici, Roberto

2015-10-01

Bone loss is typical in chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, pemphigus vulgaris, and others. It is also typical in transplantation-related inflammation and during the process of aging. While we recognized that bone loss is tightly linked to immune system activation or inflamm-aging in the form of acute, chronic active, or chronic smoldering inflammation, bone loss is typically discussed to be an "accident of inflammation." Extensive literature search in PubMed central. Using elements of evolutionary medicine, energy regulation, and neuroendocrine regulation of homeostasis and immune function, we work out that bone waste is an adaptive, evolutionarily positively selected program that is absolutely necessary during acute inflammation. However, when acute inflammation enters a chronic state due to the inability to terminate inflammation (e.g., in autoimmunity or in continuous immunity against microbes), the acute program of bone loss is a misguided adaptive program. The article highlights the complexity of interwoven pathways of osteopenia. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Evolutionary medicine and bone loss in chronic inflammatory diseases – a theory of inflammation-related osteopenia

PubMed Central

Straub, Rainer H.; Cutolo, Maurizio; Pacifici, Roberto

2015-01-01

Objective Bone loss is typical in chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, pemphigus vulgaris, and others. It is also typical in transplantation-related inflammation and during the process of aging. While we recognized that bone loss is tightly linked to immune system activation or inflammaging in the form of acute, chronic active, or chronic smoldering inflammation, bone loss is typically discussed to be an “accident of inflammation”. Methods Extensive literature search in PubMed central. Results Using elements of evolutionary medicine, energy regulation, and neuroendocrine regulation of homeostasis and immune function, we work out that bone waste is an adaptive, evolutionarily positively selected program that is absolutely necessary during acute inflammation. However, when acute inflammation enters a chronic state due to the inability to terminate inflammation (e.g., in autoimmunity or in continuous immunity against microbes), the acute program of bone loss is a misguided adaptive program. Conclusions The article highlights the complexity of interwoven pathways of osteopenia. PMID:26044543

Micrographia associated with a parietal lobe lesion in multiple sclerosis.

PubMed Central

Scolding, N J; Lees, A J

1994-01-01

The occurrence of micrographia in a 52 year old women two years after an isolated episode of painful sensory disturbance led to the diagnosis of multiple sclerosis. Her handwriting returned to normal after a course of intravenous methylprednisolone. Previous reports of movement disorders occurring in the context of multiple sclerosis are briefly reviewed. The finding on MRI studies of an enhancing lesion in the dominant parietal white matter supports Kinnier Wilson's suggestion that the anatomical origin of micrographia lies in the cerebral hemisphere rather than the corpus striatum. Images PMID:8006658

Consensus Statement on medication use in multiple sclerosis by the Spanish Society of Neurology's study group for demyelinating diseases.

PubMed

García-Merino, A; Fernández, O; Montalbán, X; de Andrés, C; Oreja-Guevara, C; Rodríguez-Antigüedad, A; Arbizu, T

2013-01-01

Treatments for multiple sclerosis therapy are rapidly evolving. It is believed that new drugs will be approved in the near future, thereby changing current indications for treatment. In this context, the Spanish Society of Neurology's study group on demyelinating diseases, which evaluates medication use in MS, has decided to draw up a consensus statement on the current indications and guidelines for multiple sclerosis treatment. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Precision medicine in chronic disease management: the MS BioScreen

PubMed Central

Gourraud, Pierre-Antoine; Henry, Roland; Cree, Bruce AC; Crane, Jason C; Lizee, Antoine; Olson, Marram P; Santaniello, Adam V.; Datta, Esha; Zhu, Alyssa H.; Bevan, Carolyn J.; Gelfand, Jeffrey M.; Graves, Jennifer A.; Goodin, Douglas E.; Green, Ari; von Büdingen, H.-Christian; Waubant, Emmanuelle; Zamvil, Scott S.; Crabtree-Hartman, Elizabeth; Nelson, Sarah; Baranzini, Sergio E.; Hauser, Stephen L.

2014-01-01

We present a precision medicine application developed for multiple sclerosis (MS): the MS BioScreen. This new tool addresses the challenges of dynamic management of a complex chronic disease; the interaction of clinicians and patients with such a tool illustrates the extent to which translational digital medicine – i.e. the application of information technology to medicine—has the potential to radically transform medical practice. We introduce three key evolutionary phases in displaying data to health care providers, patients, and researchers: visualization (accessing data), contextualization (understanding the data), and actionable interpretation (real-time use of the data to assist decision-making). Together these form the stepping-stones that are expected to accelerate standardization of data across platforms, promote evidence-based medicine, support shared decision-making, and ultimately lead to improved outcomes. PMID:25263997

Regulatory T-Cells in Chronic Lymphocytic Leukemia and Autoimmune Diseases

PubMed Central

D’Arena, Giovanni; Rossi, Giovanni; Vannata, Barbara; Deaglio, Silvia; Mansueto, Giovanna; D’Auria, Fiorella; Statuto, Teodora; Simeon, Vittorio; De Martino, Laura; Marandino, Aurelio; Del Poeta8, Giovanni; De Feo, Vincenzo; Musto, Pellegrino

2012-01-01

Regulatory T-cells (Tregs) constitute a small subset of cells that are actively involved in maintaining self-tolerance, in immune homeostasis and in antitumor immunity. They are thought to play a significant role in the progression of cancer and are generally increased in patient with chronic lymphocytic leukemia (CLL). Their number correlates with more aggressive disease status and is predictive of the time to treatment, as well. Moreover, it is now clear that dysregulation in Tregs cell frequency and/or function may result in a plethora of autoimmune diseases, including multiple sclerosis, type 1 diabetes mellitus, myasthenia gravis, systemic lupus erythematosus, autoimmune lymphoproliferative disorders, rheumatoid arthritis, and psoriasis. Efforts are made aiming to develop approaches to deplete Tregs or inhibit their function in cancer and autoimmune disorders, as well. PMID:22973497

[Therapeutic use of cannabis derivatives].

PubMed

Benyamina, Amine; Reynaud, Michel

2014-02-01

The therapeutic use of cannabis has generated a lot of interest in the past years, leading to a better understanding of its mechanisms of action. Countries like the United States and Canada have modified their laws in order to make cannabinoid use legal in the medical context. It's also the case in France now, where a recent decree was issued, authorizing the prescription of medication containing "therapeutic cannabis" (decree no. 2013-473, June 5, 2013). Cannabinoids such as dronabinol, Sativex and nabilone have been tested for the treatment of acute and chronic pain. These agents are most promising to relieve chronic pain associated with cancer, with human immunodeficiency virus infection and with multiple sclerosis. However, longer-term studies are required to determine potential long-term adverse effects and risks of misuse and addiction.

Cortical pathology in multiple sclerosis detected by the T1/T2‐weighted ratio from routine magnetic resonance imaging

PubMed Central

Righart, Ruthger; Biberacher, Viola; Jonkman, Laura E.; Klaver, Roel; Schmidt, Paul; Buck, Dorothea; Berthele, Achim; Kirschke, Jan S.; Zimmer, Claus; Hemmer, Bernhard; Geurts, Jeroen J. G.

2017-01-01

Objective In multiple sclerosis, neuropathological studies have shown widespread changes in the cerebral cortex. In vivo imaging is critical, because the histopathological substrate of most measurements is unknown. Methods Using a novel magnetic resonance imaging analysis technique, based on the ratio of T1‐ and T2‐weighted signal intensities, we studied the cerebral cortex of a large cohort of patients in early stages of multiple sclerosis. A total of 168 patients with clinically isolated syndrome or relapsing–remitting multiple sclerosis (Expanded Disability Status Scale: median = 1, range = 0–3.5) and 80 age‐ and sex‐matched healthy controls were investigated. We also searched for the histopathological substrate of the T1/T2‐weighted ratio by combining postmortem imaging and histopathology in 9 multiple sclerosis brain donors. Results Patients showed lower T1/T2‐weighted ratio values in parietal and occipital areas. The 4 most significant clusters appeared in the medial occipital and posterior cingulate cortex (each left and right). The decrease of the T1/T2‐weighted ratio in the posterior cingulate was related to performance in attention. Analysis of the T1/T2‐weighted ratio values of postmortem imaging yielded a strong correlation with dendrite density but none of the other parameters including myelin. Interpretation The T1/T2‐weighted ratio decreases in early stages of multiple sclerosis in a widespread manner, with a preponderance of posterior areas and with a contribution to attentional performance; it seems to reflect dendrite pathology. As the method is broadly available and applicable to available clinical scans, we believe that it is a promising candidate for studying and monitoring cortical pathology or therapeutic effects in multiple sclerosis. Ann Neurol 2017;82:519–529 PMID:28833433

The significance of HLA DRB1*1501 and oligoclonal bands in multiple sclerosis: clinical features and disability.

PubMed

Balnytė, Renata; Rastenytė, Daiva; Ulozienė, Ingrida; Mickevičienė, Dalia; Skordenienė, Erika; Vitkauskienė, Astra

2011-01-01

The aim of the present study was to determine the value of immunogenetic risk factors and to estimate their relationship with the clinical features and disability status of patients with multiple sclerosis in a Lithuanian population. This was a prospective study of 80 patients with multiple sclerosis. The diagnosis of multiple sclerosis was based on the revised McDonald criteria. Oligoclonal bands (OCBs) of immunoglobulin G (IgG) were tested using isoelectric focusing and IgG specific immunofixation. HLA DRB1 alleles were genotyped using polymerase chain reaction. Of all patients, 55% were positive for OCBs and 56% for HLA DRB1*1501. OCB-positive patients with multiple sclerosis had higher EDSS scores than their OCB-negative counterparts at onset of the disease (3.93±1.21 and 3.36±0.96 points, respectively; P=0.02) and during the last visit (4.31±2.06 and 3.09±1.98 points, respectively; P=0.009). The mean relapse rate was higher in the OCB-positive group compared with OCB-negative group (1.45±0.69 and 0.58±0.64, respectively; P=0.001). OCB-positive patients had higher IgG index compared with OCB-negative patients (P=0.0001). No relationship was found between HLA DRB1*1501 antigen status and the clinical features or EDSS score, and presence or absence of OCB in the present subset of patients with multiple sclerosis. The presence of oligoclonal bands in the cerebrospinal fluid of the patients with multiple sclerosis was associated with the greater number of exacerbations, higher degree of disability, and higher IgG index. There were no significant associations between the presence of HLA DRB1*1501 allele and the clinical symptoms, course of disease, or disability score.

Exploring change in a group-based psychological intervention for multiple sclerosis patients.

PubMed

Borghi, Martina; Bonino, Silvia; Graziano, Federica; Calandri, Emanuela

2018-07-01

The study is focused on a group-based cognitive behavioral intervention aimed at promoting the quality of life and psychological well-being of multiple sclerosis patients. The study investigates how the group intervention promoted change among participants and fostered their adjustment to the illness. The intervention involved six groups of patients (a total of 41 patients) and included four consecutive sessions and a 6-month follow-up. To explore change, verbatim transcripts of the intervention sessions were analyzed using a mixed-methods content analysis with qualitative data combined with descriptive statistics. The categories of resistance and openness to change were used to describe the process of change. Resistance and openness to change coexisted during the intervention. Only in the first session did resistance prevail over openness to change; thereafter, openness to change gradually increased and stabilized over time, and openness to change was then always stronger than resistance. The study builds on previous research on the effectiveness of group-based psychological interventions for multiple sclerosis patients and gives methodological and clinical suggestions to health care professionals working with multiple sclerosis patients. Implications for rehabilitation The study suggests that a group-based cognitive behavioral intervention for multiple sclerosis patients focused on the promotion of identity redefinition, a sense of coherence and self-efficacy in dealing with multiple sclerosis fosters the process of change and may be effective in promoting patients' adjustment to their illness. Health care professionals leading group-based psychological interventions for multiple sclerosis patients should be aware that resistance and openness to change coexist in the process of change. The study suggests that the duration of the intervention is a crucial factor: a minimum of three sessions appears to be necessary for group participants to develop greater openness to change and follow-up sessions should be implemented to maintain positive changes among participants. The use of qualitative instruments to evaluate group interventions captures the complexity of processes and gives useful indications to health professionals to improve rehabilitation programs.

Comprehension of confidence intervals - development and piloting of patient information materials for people with multiple sclerosis: qualitative study and pilot randomised controlled trial.

PubMed

Rahn, Anne C; Backhus, Imke; Fuest, Franz; Riemann-Lorenz, Karin; Köpke, Sascha; van de Roemer, Adrianus; Mühlhauser, Ingrid; Heesen, Christoph

2016-09-20

Presentation of confidence intervals alongside information about treatment effects can support informed treatment choices in people with multiple sclerosis. We aimed to develop and pilot-test different written patient information materials explaining confidence intervals in people with relapsing-remitting multiple sclerosis. Further, a questionnaire on comprehension of confidence intervals was developed and piloted. We developed different patient information versions aiming to explain confidence intervals. We used an illustrative example to test three different approaches: (1) short version, (2) "average weight" version and (3) "worm prophylaxis" version. Interviews were conducted using think-aloud and teach-back approaches to test feasibility and analysed using qualitative content analysis. To assess comprehension of confidence intervals, a six-item multiple choice questionnaire was developed and tested in a pilot randomised controlled trial using the online survey software UNIPARK. Here, the average weight version (intervention group) was tested against a standard patient information version on confidence intervals (control group). People with multiple sclerosis were invited to take part using existing mailing-lists of people with multiple sclerosis in Germany and were randomised using the UNIPARK algorithm. Participants were blinded towards group allocation. Primary endpoint was comprehension of confidence intervals, assessed with the six-item multiple choice questionnaire with six points representing perfect knowledge. Feasibility of the patient information versions was tested with 16 people with multiple sclerosis. For the pilot randomised controlled trial, 64 people with multiple sclerosis were randomised (intervention group: n = 36; control group: n = 28). More questions were answered correctly in the intervention group compared to the control group (mean 4.8 vs 3.8, mean difference 1.1 (95 % CI 0.42-1.69), p = 0.002). The questionnaire's internal consistency was moderate (Cronbach's alpha = 0.56). The pilot-phase shows promising results concerning acceptability and feasibility. Pilot randomised controlled trial results indicate that the patient information is well understood and that knowledge gain on confidence intervals can be assessed with a set of six questions. German Clinical Trials Register: DRKS00008561 . Registered 8th of June 2015.

Multiple Sclerosis: Hope Through Research | NIH MedlinePlus the Magazine

MedlinePlus

... turn Javascript on. Feature: Multiple Sclerosis Hope Through Research Past Issues / Spring 2012 Table of Contents Neil ... a champion for those with MS and for research to find the causes and cures for the ...

Postsecondary Education for Individuals with Multiple Sclerosis: Issues and Strategies.

ERIC Educational Resources Information Center

Yagodich, Nancy L.; Wolfe, Pamela S.; Boone, Rosalie S.

2000-01-01

Describes characteristics of multiple sclerosis and the implications of its manifestations for postsecondary education. Provides a checklist for students selecting a postsecondary institution regarding general considerations, academic accommodations, support and services, and self-assessment. (SK)

Multiple Sclerosis, Personal Stories | NIH MedlinePlus the Magazine

MedlinePlus

... please turn Javascript on. Feature: Multiple Sclerosis Personal Stories: Nicole Lemelle, Iris Young, Michael Anthony, John Cantú ... Better," an Internet video series that brings the story of MS to life through the eyes of ...