15 STUDIES IN THURSDAY'S NEWS

 PLUS: 1575 new Studies we posted from 11/1 to Wednesday 2/12 Start at the Bottom!

In patients with SSc, serum levels of ICAM-1 and P-selectin may serve as prognostic indicators of respiratory dysfunction and physical disability, respectively. Further longitudinal studies of larger populations are needed to confirm these findings.

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Seizures can occur at any stage during the course of MS, but it is more common during the early stages.

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In a real-world setting, patients with MS who switched from IFNs to fingolimod were significantly less likely to experience relapses than those who switched to GA.

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In the NARCOMS cohort, functional health literacy is high. However, lower levels of health literacy are associated with adverse health behaviors and greater health care utilization.
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In the pathogenesis of MS, this review discusses the role of different types of MMPs, including MMP-2, -3, -7, -9, -12 and -25, in the immunopathogenesis and treatment of MS.
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15 STUDIES IN WEDNESDAY'S NEWS

 PLUS: 1560 new Studies we posted from 11/1 to Tuesday 2/11 Start at the Bottom!



Seminal data regarding its use in MS, the known mechanism(s) of action, and contemporary studies focusing on efficacy and safety data will be reviewed. The role of chemotherapeutic agents in the management of MS and implications for therapeutic intervention are also discussed. 
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The best current evidence for the efficacy of glucocorticoid treatment in MS, by far, comes from the optic neuritis treatment trial, which used high-dose intravenous methylprednisolone for the first 3 days followed by an 11-day course of low-dose oral prednisone. 
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It is hoped that, through an understanding of the earliest aspects of the MS disease process, critical insights will be gained about the genesis of MS. 
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Major technical improvements in MRI hardware and pulse sequence design allow more specific and potentially more sensitive treatment metrics required for targeting outcomes most relevant to neuronal degeneration, remyelination and repair. 
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This chapter reviews the current evidence, taken from both clinical and paraclinical sources, as it relates to establishing this prognosis and provides insight to where, in the future, we need to look. 
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15 STUDIES IN TUESDAY'S NEWS

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These findings support previous systematic reviews, however publication bias cannot be excluded. The methodological conduct of studies could be improved, particularly with regard to reporting and conduct of laboratory analyses.
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Despite the long follow-up, the risk of MS appears lower in New South Wales children compared to previously reported cohorts. Radiological features are more predictive than clinical features in predicting MS. The McDonald 2010 criteria performed well although the dissemination in time criteria on baseline scans is difficult to apply to children with encephalopathy.
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Our findings suggest that higher CR in individuals with MS may mediate between cognitive performance and brain pathology. CR-related compensation may, however, fail with progression of damage. The time window of opportunity for therapeutic approaches aimed at intellectual enhancement most likely lies in the earliest disease stages.
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Further evidence of vitamin D deficiency as a causal factor, its molecular targets in MS and its prospect as a therapeutic and preventative agent are questions that warrant further study.
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Patients with ≥2 relapses annually have higher resource utilization and costs. The difference in cost was over twice as large in treatment-naïve patients versus treatment-experienced patients. HRA was also associated with an increased likelihood of starting DMT treatment (treatment-naïve patients), and switching or discontinuing DMT therapy (treatment-experienced patients).
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15 STUDIES IN MONDAY'S NEWS

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Farming and exposure to livestock may be important factors in the development of FCD among women, with this finding further revealed after the confounding effect of parity or number of children is considered.
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Results suggest that demyelinated lesions in MS mainly have a remote effect on the thalamus and that the measurement of CBF using ASL could be an objective marker for monitoring disease activity in MS.
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Here, we summarize currently accepted therapeutic principles and the drugs in late stages of development, as well as spotlighting potential novel openings for future research.
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Collaboration between neurologists and psychiatrists whilst caring for patients displaying neuropsychiatric manifestations of MS is crucial to enable more accurate diagnoses and try to improve treatment and overall prognosis. 
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In summary, in this retrospective analysis, daclizumab therapy substantially decreased the rate of brain atrophy in relapsing-remitting MS in comparison to other disease-modifying therapies, predominantly interferon β.
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15 STUDIES IN SUNDAY'S NEWS

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In this paper we present a new unsupervised approach addressing this problem with dictionary learning and sparse coding methods. We show its general applicability to the problem of lesion segmentation by evaluating our approach on synthetic and clinical image data and comparing it to state-of-the-art methods.
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In this paper we will review the substantial literature regarding experimental and clinical use of these stem cells and possible mechanisms in the treatment of MS. These results may pave the road for the utilization of stem cells for the treatment of MS.
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Long walking tests and patient-reported MSWS-12 were more appropriate than short walking tests in detecting clinically meaningful improvement after physical rehabilitation, particularly the MSWS-12 for moderate to severely disabled pwMS.
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The use of patient self-assessed outcome measures that appraise the quality of diagnosis communication is also important to allow health services to understand and meet the needs and preferences of PwMS.
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Quantitative gait assessment reveals subtle gait disorders in patients with low disability of relapsing-remitting multiple sclerosis. The impact of different cognitive domains on gait induces specific gait disturbances that highlight the strong interaction between gait and cognition.
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15 STUDIES IN SATURDAY'S NEWS

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Studies are needed to further clarify why suicide ideation and suicidal behavior are associated with neurological diseases, in order to improve quality of life, alleviate patient distress, and prevent nonfatal and fatal suicide attempts in veteran and non-veteran populations.
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Obesity in childhood or adolescence is associated with an increased risk of pediatric-onset and adult-onset multiple sclerosis
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Autoimmune disorders are rare, but some of them tend to occur together with MS at a higher rate than in controls. Although women are generally more prone to ADs than men, significantly increased occurrence of other ADs were only found in male MS patients.
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Paternal MS and MS-related clinical factors were not significantly associated with birth outcomes (p>0.05). This study provides assurance to expecting fathers with MS and their families.
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This study showed that PET imaging of demyelination and remyelination processes in focal lesions is feasible.
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15 STUDIES IN FRIDAY'S NEWS

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A study was done to assess the cost-effectiveness of the Disease Modifying Treatments (DMT), Glatiramer Acetate (GA) and Interferon beta-1a (IFN) in monotherapy alone and in combination for the prevention of relapses among Spanish patients aged between 18 and 60 years old with established Relapsing-Remitting Multiple Scerosis (RRMS).
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Article reviews the current understanding of the interactions between multiple sclerosis (MS) and pregnancy, and implications for reproductive counseling. This is a key topic in MS because the typical patient is a young woman of childbearing age.Pregnancy has a profound effect on MS disease activity. Identification of the responsible mechanisms for this effect should lead to new disease insights and therapeutic strategies. 
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Pain-related mood influences pain perception differently in fibromyalgia and multiple sclerosis.
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Gait disorders need to be identified and managed early in the course of MS, using a multimodal approach that needs to be adjusted over time based on the results of periodic assessments.
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Fatigue needs to be recognized as an important condition that is not only a symptom but may also be quantified and can be modified by various measures depending on the underlying cause.
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15 STUDIES IN THURSDAY'S NEWS

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Current guidelines have recognized the benefits of early treatment of MS with DMTs. However, there are a number of barriers to implementing early MS treatment. Early diagnosis and treatment of MS can be hindered because patients may delay consulting a physician about their neurological symptoms or may be reluctant to start DMT. Read study at National Institute of Health

Due to the current lack of appropriate clinical guidance and insufficient head-to-head data on disease-modifying drugs, strategies for health plans and clinical management have been designed using the best available evidence. Undoubtedly, management of this class will continue to evolve with the launch of newer agents.
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A period of diagnostic uncertainty regarding the transition from RRMS to SPMS existed in many of our patients. Potential reasons included the subtle nature of early progressive disease and caution in applying a progressive label, in light of the lack of evidence-based treatments as well as third-party payer concerns. Delay in definitive identification of an SPMS phenotype has a variety of implications related to patient care and research.
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This study supports the concept that modifications of the tear proteome can reflect biological abnormalities associated with multiple sclerosis and perhaps other inflammatory conditions affecting the CNS. In addition, alpha-1-antichymotrypsin elevation in tear fluid emerges as a promising biomarker for the diagnosis of multiple sclerosis.

The present study examined the functioning of explicit and implicit memory in MS. Results showed that implicit memory was not significantly impaired in the MS subjects, and that they were impaired on recall but not recognition. A correlation was found between implicit memory performance and disability status in MS patients. 

15 STUDIES IN WEDNESDAY'S NEWS

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Control of spasticity in a multiple sclerosis model using central nervous system-excluded CB1 cannabinoid receptor agonists 

Vowel Acoustics in Parkinson's Disease and Multiple Sclerosis: Comparison of Clear, Loud, and Slow Speaking Conditions

Predictors of effectiveness of multidisciplinary rehabilitation treatment on motor dysfunction in multiple sclerosis.

A Randomized, Double-Blind, Placebo-Controlled Trial of Duloxetine for the Treatment of Pain in Patients with Multiple Sclerosis.

Fatty fish intake is associated with decreased occurrence of multiple sclerosis

15 STUDIES IN TUESDAY'S NEWS

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Magnetic susceptibility of MS lesions increased rapidly as it changed from enhanced to nonenhanced, it attained a high susceptibility value relative to NAWM during its initial few years (approximately 4 years), and it gradually dissipated back to susceptibility similar to that of NAWM as it aged, which may provide new insight into pathophysiologic features of MS lesions.

In a cohort with different stages of MS, higher EA attenuated the negative effects of white matter lesion burden and third ventricle width (suggestive of thalamic atrophy) on cognitive performance. Actively enhancing cognitive reserve might thus be a means to reduce or prevent cognitive problems in MS in parallel to disease modifying drugs.

These data suggest that retrograde (trans-synaptic) axonal degeneration stops at the inner nuclear layer, a neuronal network capable of plasticity. In contrast, there seems to be no neuroplasticity of the primary visual cortex, rendering the structure vulnerable to anterograde (trans-synaptic) degeneration.

Simultaneous characterizations of changes in tonic and phasic reflexes and nonreflex changes in joint elastic stiffness and viscosity in neurological disorders may help us gain insight into mechanisms underlying spasticity and develop impairment-specific treatment.

Very rapid functional changes in the excitability of cortical circuits involved in motor control can be induced by steroids, before any process of remyelination or axonal regeneration has time to occur. The net effect of steroids on the balance between intracortical GABAergic inhibition and glutamatergic facilitation was in favour of weaker inhibition or stronger facilitation, which could lead to improving the motor performance in MS patients.

15 STUDIES IN MONDAY'S NEWS

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The majority of Italian neurologists participating in our study have a good perception of their ability to manage this difficult communicating process and believe in the great effect this moment may have on a life-long disease experience. Improving communication skills may help the therapeutic alliance, enhancing patients' acceptance of the disease, as well as motivation and adherence to treatment.

It is possible that, with further such supportive data, international guidelines on MS treatment in young women who intend to get pregnant may need to be revised.

A significant interaction between Alerting and Executive Control was also found in the MS patients (p = .007). Early relapsing-remitting multiple sclerosis particularly affects the Alerting domain of attention, whereas the Orienting and Executive Control domains are not affected.

The GM is atrophic in MS. Although lower WM volume is associated with greater disability, as might be expected, WM volume was on average in the normal range. This paradoxical result might be explained by the presence of coexisting pathological processes, such as tissue damage and repair, that cause both atrophy and hypertrophy and that underlie the observed disability.

ApEn results revealed that the natural fluctuations present during gait in the stride length and step width time series are more regular and repeatable in patients with MS. These changes implied that patients with MS may exhibit reduced capacity to adapt and respond to perturbations during gait.

15 STUDIES IN SUNDAY'S NEWS

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In this small, uncontrolled pilot study, there was a significant improvement in fatigue in those who completed the study. Given the small sample size and completer rate, further evaluation of this multimodal therapy is warranted.

These data suggest that retrograde (trans-synaptic) axonal degeneration stops at the inner nuclear layer, a neuronal network capable of plasticity. In contrast, there seems to be no neuroplasticity of the primary visual cortex, rendering the structure vulnerable to anterograde (trans-synaptic) degeneration.

The number of patients becoming pregnant during fingolimod therapy remains small and does not permit firm conclusions to be drawn about fetal safety of fingolimod in humans. Given the known risks of teratogenicity in animals and the present data, women of childbearing potential should use effective contraception during fingolimod therapy and for 2 months after discontinuation.

The relapse rate in children with multiple sclerosis is higher than in adult-onset disease. Following acute treatment, recovery after the first attacks is usually excellent, but patients with childhood-onset multiple sclerosis reach permanent disability or enter the secondary progressive disease course 10 years younger than patients with adult-onset multiple sclerosis.

Currently, various pharmacological agents such as antiepielptics, non-steroidal anti-inflammatory agents, and even corticosteroids are used to suppress various painful conditions associated with MS. Non-pharmacological procedures such as massage therapy have also been used in the treatment of MS patients. The authors present a review of recent findings in pathophysiology and management of pain in MS patients.

15 STUDIES IN SATURDAY'S NEWS

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The results obtained in the current study demonstrate that absolute myelin water content can reliably be determined in a multicentre environment using standard MR sequences. The optimised protocol allows for a measurement of four quantitative parameters with full brain coverage in only 10 min. This might expedite a more widespread future use of quantitative MRI methods for clinical research and diagnosis.

The results demonstrate that paired analysis can strongly improve longitudinal correlation (from -0.148 to -0.303 in this sample) and may produce segmentations that are more sensitive to clinically relevant changes.

peptide-based immunotherapy could provide improved clinical status or life-long remission to MS patients. Substantiation of this premise requires a follow-up examination by other investigators and institutions with larger and more extensive clinical trials.

The changing landscape of voltage-gated calcium channels in neurovascular disorders and in neurodegenerative diseases.

Although cognitive performance as measured on the PASAT-3s does not correlate with a patient's perceived quality of life in a multivariate model, it remains an important predictor for the patient's usual activities.

15 STUDIES IN FRIDAY'S NEWS

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Magnetic susceptibility of MS lesions increased rapidly as it changed from enhanced to nonenhanced, it attained a high susceptibility value relative to NAWM during its initial few years (approximately 4 years), and it gradually dissipated back to susceptibility similar to that of NAWM as it aged, which may provide new insight into pathophysiologic features of MS lesions.

In a cohort with different stages of MS, higher EA attenuated the negative effects of white matter lesion burden and third ventricle width (suggestive of thalamic atrophy) on cognitive performance. Actively enhancing cognitive reserve might thus be a means to reduce or prevent cognitive problems in MS in parallel to disease modifying drugs.

Grey matter damage - global and regional - has the potential to become a marker of disease activity, complementary to the currently used magnetic resonance markers (global brain atrophy and T2 hyperintense lesions). Furthermore, it may improve the prediction of the future disease course and response to therapy in individual patients and may also become a reliable additional surrogate marker of treatment effect.

results confirm the important role of the immune system and specifically B cells in MS and suggest that MS risk variants exert a gene regulatory role. Previous studies assessing MS risk variants in T cells may be missing important effects in B cells. Similar analyses in other immunological cell types relevant to MS and functional studies are necessary to fully elucidate how genes contribute to MS pathogenesis.

Fatigue management program outcomes for people with MS are moderated by age, gender, and impairment.

15 STUDIES IN THURSDAY'S NEWS

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Employment status was an explanatory variable for physical health and mental health in the younger patients. EDSS played a significant role in physical health for all patients. A vocational rehabilitation program could prevent eventual nonemployment and improve health outcomes in older MS people.

Simultaneous characterizations of changes in tonic and, phasic reflexes and nonreflex changes in joint elastic stiffness and, viscosity in neurological disorders may help us gain insight into, mechanisms underlying spasticity and develop impairment-specific, treatment.

Using an active prospective surveillance system and the McDonald criteria for first MS diagnosis the age-related incidence of pediatric MS in Germany was uncovered and is more common than in previous estimates. Thorough application of McDonald criteria and inclusion of spinal MRI data allowed for early diagnosis in almost 90% of cases.

A high prevalence of urinary symptoms and urodynamic dysfunctions in patients with CISs and an association of urinary symptoms with quality of life measures were found. These results highlight the importance of identifying and optimally treating urinary symptoms also at the very early stages of MS.

The inflammatory mechanisms associated with lesion formation in MS are to a large extent reflected in experimental models of inflammatory demyelination, such as autoimmune encephalomyelitis. This is not the case for the amplification mechanisms of oxidative injury, which mainly operate in the progressive stage of the disease. GLIA 2014.

15 STUDIES IN WEDNESDAY'S NEWS

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These data support the view that cerebellar abnormalities contribute to disability, including cognitive impairment in MS.

primary position upbeat nystagmus, PPUN,  is an infrequent, ocular manifestation noted during an acute attack of MS, and was observed in 5% of the present cases. Brainstem lesions in these cases primarily involved the pontine tegmentum and the caudal medulla.

Until fingolimod came along, the first Food and Drug Administration-approved pill for relapsing-remitting multiple sclerosis (RRMS), teratogenicity of multiple sclerosis (MS) drugs had not been a big issue

Future studies should explore the association between the local availability and affordability of home-based services and physician attitude about community-based care management of disabled patients.

These results suggest that, although attributional style appears to be an important construct in MS, it does not seem to be related directly to depressive symptoms; rather, it is related to more perceived stress, which in turn is related to increased depressive symptoms. 

15 STUDIES IN TUESDAY'S NEWS

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Subjects with MS are more likely to develop spasticity especially if the lesions are numerous and affect the corticospinal tracts, callosal radiations extensively or brainstem.

This report presents the case of a patient with MS and clinical features mimicking frontotemporal dementia due to clear-cut cortical gray matter involvement in the left frontal lobe.

The identification of those patients with MS with poor HRQOL may be important in assessing the risk of future disability progression. Clearly, impaired HRQOL should be one of the primary concerns amongst clinicians who provide treatment to patients affected by MS.

This review examines the evidence that circulating vitamin D levels provide a surrogate measure of sun exposure and that it is the other molecules and pathways induced by sun exposure, rather than vitamin D-driven processes, that explain many of the benefits often attributed to vitamin D.

Walking assessments had high reliability and were correlated with related measures, including the 12-item multiple sclerosis walking scale (MSWS-12)

15 STUDIES IN MONDAY'S NEWS

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Health professionals treating people with MS and their caregivers should be sensitive to the impact caregiving has on the emotional needs of caregivers and to the unique support needs of spousal caregivers.   

Walking difficulties are common in neurological and other disorders, as well as among the elderly. There is a need for reliable and valid instruments for measuring walking difficulties in everyday life since existing gait tests are clinician rated and focus on situation specific capacity.

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.

The results of this study can inform the design and implementation of self-management interventions. Experiences described by participants are consistent with other qualitative reports suggesting the active role people with MS play in managing their condition. 

The association of higher sun exposure with a better outcome in relapsing-onset MS may be explained by either a protective effect or reverse causality. Mechanisms underlying sun sensitivity might influence progression in progressive-onset MS.

15 STUDIES IN SUNDAY'S NEWS

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findings provide relevant insights into how vitamin D influences the immune system and the risk of MS through VDR interactions with the chromatin state inside MS regions. Furthermore, the data provide additional evidence for an important role played by B cells in MS. Further analyses in other immune cell types and functional studies are warranted to fully elucidate the role of vitamin D in the immune system.

MS incidence rose markedly over 3 decades in a genetically stable population in tandem with a transition from rural to urban living, thus possibly implicating environmental factors introduced by urbanization.

This study demonstrates that depression is not the only cause of fatigue in patients with MS and it is also associated with sleep disorders, so this complaint should be carefully evaluated and managed in these patients.

Increased awareness of the risk of hip fracture is warranted in patients with MS, especially in those who have recently been prescribed antidepressants or hypnotics/anxiolytics.

Mental health care should be provided promptly after diagnosis, with regular screening and interventions that include family members as indicated thereafter. Mental health providers should be familiar with MS, collaborate with neurologic care providers and provide services on-site at MS centers.

15 STUDIES IN SATURDAY'S NEWS

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The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here. 

As emerging therapies such as alemtuzumab are approved for the treatment of MS, nurses specializing in the care of MS patients will make increasingly significant contributions to the education of patients, caregivers, and other health-care providers about these therapies' efficacy, tolerability, safety, and administration.

the study was to evaluate the stimulated production of interferon-gamma (IFNγ) by peripheral CD3+CD4+ T lymphocytes in patients with multiple sclerosis (MS) with regard to the degree of fatigue, and to investigate relationships between immunological parameters, level of depression and clinical variables.

Statistical analysis revealed that PwMS walked slower, with fewer, shorter, wider steps and spent a greater percentage of a gait cycle in double support than controls. Additionally, PwMS had greater variability in the time between steps, single support percent and step width than controls.

The theory that iron deposition in the brain contributes to MS pathogenesis has caused uncertainty among patients as to whether they should avoid iron.