Darcy Cox

Association between stressful life events and exacerbation in multiple sclerosis: a meta-analysis

Abstract Objective To quantify the association between stressful life events and exacerbations of multiple sclerosis. Data sources PubMed, PsychInfo, and Psychological Abstracts searched for empirical papers from 1965 to February 2003 with terms “stress”, “trauma”, and “multiple sclerosis”. Review methods Three investigators independently reviewed papers for inclusion/exclusion criteria and extracted the relevant data, including methods, sample statistics, and outcomes. Results Of 20 studies identified, 14 were included. The meta-analysis showed a significant increase in risk of exacerbation in multiple sclerosis after stressful life events, with a weighted average effect size of d = 0.53 (95% confidence interval 0.40 to 0.65), P < 0.0001. The studies were homogenous, q = 16.62, p = 0.22, i2 = 21.8%. Neither sampling nor study methods had any effect on study outcomes. Conclusions There is a consistent association between stressful life events and subsequent exacerbation in multiple sclerosis. However these data do not allow the linking of specific stressors to exacerbations nor should they be used to infer that patients are responsible for their exacerbations. Investigation of the psychological, neuroendocrine, and immune mediators of stressful life events on exacerbation may lead to new behavioural and pharmacological strategies targeting potential links between stress and exacerbation.

The Goldman Consensus statement on depression in multiple sclerosis

Background. In January 2002 the New York City Chapter of the National Multiple Sclerosis Society convened a panel of experts to review the issue of depressive affective disorders associated with multiple sclerosis (MS). This Consensus Conference was supported by a grant from the Goldman family of New York City. Results. The panel reviewed summaries of current epidemiologic, neurobiologic, and therapeutic studies having to do with depressive disorders among MS patient populations. Depressive disorders occur at high rates among patients with MS, and there is reason to believe that the immunopathology of the disease is involved in the clinical expression of affective disorders. The depressive syndromes of MS have a major, negative impact on quality of life for MS sufferers, but are treatable. At the present time, most MS patients with depression do not receive adequate recognition and treatment. Conclusions. The Goldman Consensus Conference Study Group provides recommendations for improved screening, diagnosis, and clinical management for depressive affective disorders among patients suffering from MS.

Reliable screening for neuropsychological impairment in multiple sclerosis

In an earlier study, we developed the Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) to assist in the screening for neuropsychological (NP) impairments. Self-report MSNQ scores correlated significantly with measures of depression, whereas informant-report MSNQ scores correlated with cognitive performance, but not depression. This study was criticized for use of a small sample and lack of data regarding normal performance and test -retest reliability. The present study was designed to replicate the earlier work with a larger sample of patients and normal controls obtained from multiple sites. We also evaluated the test -retest reliability and predictive validity of the MSNQ. The sample included 85 multiple sclerosis (MS) patients and 40 normal controls, matched on demographic variables. All participants completed the MSNQ and underwent NP testing. Thirty-four patients were re-examined at one week. Pearson and ANOVA techniques were utilized for univariate comparisons. Bayesian statistics were calculated to assess predictive validity. Patient self- and informant-report MSNQ scores differed from normal and test -retest reliability indices were high. Both self- and informant-reports were correlated with cognitive dysfunction and depression scales. Self-report MSNQ scores correlated more strongly with depression than cognitive performance, whereas the opposite pattern was observed with informant-report scores. Bayesian statistics showed that informant-report MSNQ scores predict cognitive impairment and patient self-report scores identify patients with cognitive impairment or depression. It is concluded that the MSNQ is useful, although patient self-reports may be exaggerated in depressed patients or reduced in patients with severe cognitive impairment.

Moderating effects of coping on the relationship between stress and the development of new brain lesions in multiple sclerosis.

Objective Many patients with multiple sclerosis (MS) report that stress can trigger disease exacerbations. Considerable research has supported a relationship between stress and both clinical exacerbation and the development of new brain lesions. However, these relationships are not always consistent either within patients or across patients, suggesting the presence of moderators. This study examined the hypothesis that coping moderates the subsequent relationship between stress and the development of new brain lesions in MS. Methods Thirty-six patients (mean age = 44.4; 22 women, 14 men) with relapsing forms of MS were assessed once every 4 weeks for 28–100 weeks. New brain lesions were identified using monthly Gd+ MRI. Stress was measured within 24 hours before MRI using a modified version of the Social Readjustment Rating Scale that assessed Conflict and Disruption in Routine. Coping was measured at baseline using the Coping with Health Injuries and Problems questionnaire, which produces four scales: distraction, instrumental, palliative, and emotional preoccupation. Data were analyzed using mixed effects logistic regression to account for within-subject correlations. Analyses were lagged such that stress assessments predicted new Gd+ MRI brain lesions 8 weeks later. Results As reported previously, stress was significantly related to the development of new Gd+ brain lesions 8 weeks later (OR = 1.62, p = .009). Greater use of distraction was found to be a significant moderator of the relationship between stress and new Gd+ lesions (OR = 0.69, p = .037) such that greater use of distraction was associated with a decreased relationship between stress and new Gd+ lesions. Increased instrumental coping was marginally associated with a decreased relationship between stress and new Gd+ lesions (OR = 0.77, p = .081), while increased emotional preoccupation was marginally associated with an increased relationship between stress and new Gd+ lesions (OR = 1.46, p = .088). There was no significant moderating effect for palliative coping (p = .27) and no significant main effects for any coping variables and the subsequent development of new Gd+ brain lesions (p values > .21). Conclusions These findings provide modest support for the hypothesis that coping can moderate the relationship between stress and the MS disease activity. Several limitations in this study are discussed. While these findings suggest areas of potentially fruitful research, readers are cautioned that these are preliminary results; inferences regarding the clinical importance of these findings are premature.

Teaching patients to self-inject: pilot study of a treatment for injection anxiety and phobia in multiple sclerosis patients prescribed injectable medications.

Medications are increasingly being developed for chronic illnesses that require regular injection. Usually it is recommended that, if possible, patients learn to inject themselves. Self-injection is associated with better adherence than injection by family or clinics. Yet large numbers of people have difficulty learning to self-inject due to injection anxiety or phobia. We present data from eight patients who went through a manualized 6-week cognitive behavioral treatment designed to increase self-efficacy and reduce anxiety. These patients were diagnosed with multiple sclerosis, were prescribed weekly intramuscular interferon beta-1a injections, and were unable to self-inject due to anxiety or phobia. Seven of the eight patients were able to inject within the 6 weeks of therapy. The eighth patient self-injected during an additional seventh session. Seven of the eight patients continued to self-inject at 3-month follow-up. Patients showed significant improvements in self-injection self-efficacy and injection anxiety.

Self-Injection Anxiety Training: a treatment for patients unable to self-inject injectable medications

Anxiety and phobia frequently prevent patients with multiple sclerosis (MS) from self-injecting their injectable disease-modifying medications. This small, randomized, controlled trial tested the efficacy of a six-session nurse-administered programme to teach self-injection to patients with MS, who, due to anxiety or phobia, were unable to self-inject their injectable medications. Participants were 30 patients with MS who were prescribed interferon beta-1a (IFNβ-1a) administered via weekly intramuscular injection. All patients were unable to self-inject due to anxiety or phobia. Patients were randomized to either the six-session Self-Injection Anxiety Therapy (SIAT) or a control telephone support condition modelled on the support programme offered by the manufacturer of IFNβ-1a. Four patients dropped out of SIATwhile three dropped out of the control condition. Eight patients receiving SIAT, compared to three control patients, were able to self-inject after six weeks of treatment. SIAT patients were significantly more likely to achieve self-injection at treatment cessation, compared to telephone control patients, in completer analyses (p=0.022), however, this only reached a trend in intent-to-treat analyses (p=0.058). These findings suggest that SIAT is a potentially valuable intervention to teach self-injection skills to injection phobic and anxious patients, and should be investigated more thoroughly in a larger clinical trial.

The unique impact of changes in normal appearing brain tissue on cognitive dysfunction in secondary progressive multiple sclerosis patients

Objective: The purpose of this study was to examine the relationships between cognitive functioning, whole brain magnetic transfer ratio (MTR) imaging, supratentorial 1H-magnetic resonance spectroscopy imaging (1HMRSI), and conventional T1 and T2 imaging in a homogenous sample of SPMS patients. Methods: Nineteen patients underwent a single 90-min imaging session that obtained T1-and T2-weighted images and MTR. 1HMRSI was obtained on 14 of these patients. Patients underwent a neuropsychological battery, which was used to create an integrated measure of cognitive impairment. Cognitive impairment was the dependent variable in two hierarchical multiple regression analyses in which T2 lesion load, T1 lesion load, and MTR or NAA/Cr were entered sequentially. Results: MTR was significantly related to cognitive functioning (ΔR2= 0.22, P= 0.02) after accounting for T2 lesion load (ΔR2=0.33, P= 0.01) and T1 lesion load (ΔR2= 0.00, P=0.98). NAA/Cr was not significantly related to cognitive functioning. Conclusions: Cognitive dysfunction may act as a clinical marker of normal appearing brain tissue pathology in multiple sclerosis.

Brain lesion volume and neuropsychological function predict efficacy of treatment for depression in multiple sclerosis

This study examined the effects of brain lesions and neuropsychological impairment on the efficacy of treatment for depression in patients with comorbid diagnoses of multiple sclerosis (MS) and major depressive disorder (MDD). Thirty patients meeting criteria for MS and MDD received 1 of 3 16-week treatments for depression and were followed for 6 months following treatment cessation. T2-weighted magnetic resonance imaging and neuropsychological evaluations were also obtained. End-of-treatment Beck Depression Inventory (BDI; A. T. Beck, C. H. Ward, M. Mendelson, J. Mock, & J. Erbaugh, 1961) results residualized for baseline BDI were related to right temporal periventricular lesion volume (R2=.32, p=.002) and left temporal grey-white junction lesion volume (R2=.19, p=.02) but were not statistically related to lesion volume in any other brain region or to neuropsychological function. BDI results at 6-month follow-up, residualized for end-of-treatment BDI, were predicted by total lesion volume (R2=.22, p=.005), lesion volume in many discrete areas, and neuropsychological functioning (R2=.29, p=.0009). The effect of total lesion volume on 6-month follow-up BDI results was fully mediated by neuropsychological function.

Managing difficulties with adherence to injectable medications due to blood, injection, and injury phobia and self-injection anxiety

Injection phobia has long been known to interfere with the successful delivery of medical and dental care. Increasingly, as new biological medications administered through regular injection are developed, the inability to self-inject due to anxiety is reducing initiation and adherence to treatment. The prevalence of injection phobia ranges from 7–22% of the general population, while the inability to self-inject may also be increasingly prevalent.Specific phobia — blood, injection, and injury (BII) — is a diagnosis that is characterized by phobic reactions to exposure to injections, injury, or blood, leading to avoidance of such situations, or tolerating these situations only under extreme emotional duress. While the literature on health outcomes related to injection phobia is somewhat limited, injection phobia has been shown to contribute to poor adherence to treatment regimens, or to discontinuance of treatment altogether in diabetes mellitus and multiple sclerosis. Hypotheses about possible psychological and genetic mechanisms have been developed, as well as high psychiatric comorbidities that may contribute to injection anxiety and phobia, or complicate medical treatment. A number of psychological factors, including poor self-efficacy about self-injecting, beliefs about the benefits and risks associated with injecting, and feelings of disgust may contribute to injection phobia. Increased occurrence of vasovagal responses during or following injection may also increase the risk of injection phobia. Because injection phobia can prevent or interfere with the delivery of needed medications, it is believed that injection phobia and self-injection anxiety can have health consequences, however, research in this area is lacking. Cognitive behavioral therapies, including both exposure and cognitive restructuring, have been shown to be an effective treatment.

Treating self-injection phobia in patients prescribed injectable medications: A case example illustrating a six-session treatment model

This article provides a case description of a patient with multiple sclerosis prescribed interferon beta-1a (IFNβ-1a), a weekly intramuscular injection, who met DSM-IV criteria for specific phobia, blood/injection type. This patient successfully completed a 6-week manualized cognitive-behavioral treatment for self-injection anxiety. Issues presented include dealing with vasovagal responses and examples of typical dysfunctional thoughts related to self-injecting. The patient was able to successfully self-inject following treatment, and gains were maintained for 18-month follow-up.