Psychological stress and the subsequent appearance of new brain MRI lesions in MS

Mohr, David C.; Goodkin, Donald E.; Bacchetti, Peter; Boudewyn, Arne C.; Huang, Liwen; Marrietta, P.; Cheuk, W.; Dee, Brian M.

doi:10.1212/wnl.55.1.55

Cited by 174 publications

(171 citation statements)

References 39 publications

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“…These findings are consistent with epidemiologic studies showing that stressful life events increase the risk of new Gdϩ MRI lesions 2 and MS exacerbations 20 and provide more conclusive evidence of the link between stress and MRI activity, given that the RCT design eliminates potential biases that are inherent in epidemiologic studies. Our results are especially encouraging since we selected our participants for higher disease activity.…”

supporting

confidence: 88%

“…2 Planning for 6 monthly scans during the treatment period, we expected 50% of control participants to have Gdϩ lesions on the first scan, dropping to 40% by 24 weeks. Using an intent-to-treat (ITT) analysis, ␣ of 0.05, power of 0.80, 2-tailed testing, and a 10% reduction in the occurrence of Gdϩ lesions in the treated arm compared to the control group, we required 60 participants in each group for a total sample size of approximately 120 participants.…”

Section: Statistical Analysesmentioning

confidence: 99%

“…1 Stressful life events have also been shown to precede new gadolinium-enhancing (Gdϩ) MRI brain lesions, a more objective measure of disease activity, by approximately 4 -8 weeks. 2 Several studies have indicated that more adaptive coping moderates the effect of stress on the development of new Gdϩ lesions 3 and is associated with fewer exacerbations. 4 Cognitive behavioral stress management therapies (SMTs) teach coping skills that are aimed at enhancing a patient's ability to prevent stressful events from occurring and improving the capacity to manage their responses to those stressful events that do arise.…”

mentioning

confidence: 99%

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A randomized trial of stress management for the prevention of new brain lesions in MS

et al. 2012

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Objectives: This trial examined the efficacy of a stress management program in reducing neuroimaging markers of multiple sclerosis (MS) disease activity. Methods:A total of 121 patients with relapsing forms of MS were randomized to receive stress management therapy for MS (SMT-MS) or a wait-list control condition. SMT-MS provided 16 individual treatment sessions over 24 weeks, followed by a 24-week post-treatment follow-up. The primary outcome was the cumulative number of new gadolinium-enhancing (Gdϩ) brain lesions on MRI at weeks 8, 16, and 24. Secondary outcomes included new or enlarging T2 MRI lesions, brain volume change, clinical exacerbation, and stress.Results: SMT-MS resulted in a reduction in cumulative Gdϩ lesions (p ϭ 0.04) and greater numbers of participants remained free of Gdϩ lesions during the treatment (76.8% vs 54.7%, p ϭ 0.02), compared to participants receiving the control treatment. SMT-MS also resulted in significantly reduced numbers of cumulative new T2 lesions (p ϭ 0.005) and a greater number of participants remaining free of new T2 lesions (69.5% vs 42.7%, p ϭ 0.006). These effects were no longer detectable during the 24-week post-treatment follow-up period. Conclusions:This trial indicates that SMT-MS may be useful in reducing the development of new MRI brain lesions while patients are in treatment. Classification of evidence:This study provides Class I evidence that SMT-MS, a manualized stress management therapy program, reduced the number of Gdϩ lesions in patients with MS during a 24-week treatment period. This benefit was not sustained beyond 24 weeks, and there were no clinical benefits.Trial registration: ClinicalTrials.gov, number NCT00147446. Neurology ® 2012;79:412-419 GLOSSARY BIPS ϭ Brief Inventory of Perceived Stress; DMT ϭ disease-modifying therapy; EDSS ϭ Expanded Disability Status Scale; Gd؉ ϭ gadolinium-enhancing; ITT ϭ intent-to-treat; LES ϭ Life Events Scale; MS ϭ multiple sclerosis; NNT ϭ number needed to treat; RCT ϭ randomized controlled clinical trial; SMT-MS ϭ stress management therapy for multiple sclerosis; UCSF ϭ University of California San Francisco.Accumulating evidence suggests an association between stress and disease activity in multiple sclerosis (MS).1 Stressful life events have also been shown to precede new gadolinium-enhancing (Gdϩ) MRI brain lesions, a more objective measure of disease activity, by approximately 4 -8 weeks.2 Several studies have indicated that more adaptive coping moderates the effect of stress on the development of new Gdϩ lesions 3 and is associated with fewer exacerbations. 4 Cognitive behavioral stress management therapies (SMTs) teach coping skills that are aimed at enhancing a patient's ability to prevent stressful events from occurring and improving the capacity to manage their responses to those stressful events that do arise.The primary aim of this multicenter randomized controlled clinical trial (RCT) was to examine the efficacy of a well-validated SMT for MS (SMT-MS) 5 in reducing the occurrence of new Gdϩ les...

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supporting

confidence: 88%

Section: Statistical Analysesmentioning

confidence: 99%

mentioning

confidence: 99%

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A randomized trial of stress management for the prevention of new brain lesions in MS

et al. 2012

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“…Although human clinical studies have provided evidence that stress is correlated with disease onset and subsequent disease exacerbations (e.g., Mohr et al, 2000 andMohr, Hart, Julian, Cox, andPelletier, 2004), surprisingly little is known about the underlying mechanisms. Here we discuss research from http://www.apa.org/science/psa/meagher.html our laboratory suggesting that stress-induced increases in central nervous system inflammation mediate the adverse effects of stress in an animal model of MS.…”

Section: Introductionmentioning

confidence: 99%

Cytokines Mediate the Adverse Effects of Social Stress in an Animal Model of Multiple Sclerosis

Meagher¹,

Jane²,

Welsh³

2008

PsycEXTRA Dataset

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“…Most recently, acute stress was shown to increase BBB permeability to 99 Technetium-g1uceptatethrough the involvement ofbrain mast cells (7) and corticotropinreleasing-hormone (eRR) (7). It is, therefore, of interest that MS symptoms can be precipitated by psychological stress (8)(9); a meta analysis and two recent publications confirmed a correlation between stress and MS attacks (10).…”

mentioning

confidence: 99%

A Pilot, Open Label, Clinical Trial Using Hydroxyzine in Multiple Sclerosis

Logothetis¹,

Mylonas²,

Baloyannis

et al. 2005

Int J Immunopathol Pharmacol

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Multiple sclerosis (MS) is an autoimmune disorder of myelin destruction. Blood-brain-barrier (BBB) disruption precedes pathological or clinical findings and could involve mediators from perivascular brain mast cells, such as histamine and vascular endothelial growth factor (VEGF). Mast cells could be activated by many triggers, including acute stress that has been correlated with MS exacerbations. We considered that the histamine-1 (HI) receptor antagonist hydroxyzine, which also partially inhibits brain mast cells and has anxiolytic properties, may reduce MS symptoms. This open label, pilot, clinical trial investigated the effect on MS of an oral solution of hydroxyzine (100 mg per day), together with caffeine (200 mg per day) to reduce sedation. Twenty patients (8 males; 12 females) with relapsing-remitting or relapsing-progressive MS completed the study (12 ± 1 months) and were evaluated using disability scales. Most patients on hydroxyzine (75%) remained stable or improved neurologically and all but one showed improved mood. Hydroxyzine could be used as an adjuvant in MS, but the small number of patients enrolled and the short duration of the study precludes any definitive conclusions. A double-blind, placebo-controlled study is warranted.Multiple sclerosis (MS) is a human demyelinating disease characterized by brain edema and perivascular infiltrates ("cuffing") of mononuclear cells accompanied by various degrees of neurologic disability (1-2). Affected areas fill with fibrotic tissue forming the MS plaques that also contain activated mast cells (3). Blood-brain-barrier (BBB) breakdown precedes any pathological or clinical signs of MS (4-5). Acute stress can disrupt the BBB in rats (6). Most recently, acute stress was shown to increase BBB permeability to 99 Technetium-g1uceptatethrough the involvement ofbrain mast cells (7) and corticotropinreleasing-hormone (eRR) (7). It is, therefore, of interest that MS symptoms can be precipitated by psychological stress (8-9); a meta analysis and two recent publications confirmed a correlation between stress and MS attacks (10).Mast cells are typically activated by 19E and specific antigen in allergic reactions, as well as in innate and acquired (11) immunity. They have also been increasingly implicated in neuroinflammatory conditions, especially those worsened by stress (12). Mast cells have been associated with brain demyelination (13)(14) and are activated in

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Psychological stress and the subsequent appearance of new brain MRI lesions in MS

Abstract: These data provide support for the notion that conflict and disruption in routine are related to subsequent disease activity in MS. However, this relationship is not sufficiently robust to predict clinical exacerbations reliably in individual patients.

Cited by 174 publications

References 39 publications

A randomized trial of stress management for the prevention of new brain lesions in MS

A randomized trial of stress management for the prevention of new brain lesions in MS

Cytokines Mediate the Adverse Effects of Social Stress in an Animal Model of Multiple Sclerosis

A Pilot, Open Label, Clinical Trial Using Hydroxyzine in Multiple Sclerosis

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