Stress Management May Prevent MS Lesions
Stress Management May Prevent MS Lesions
July 11, 2012 — Multiple sclerosis (MS) patients who completed a course of behavioral stress management had fewer new gadolinium-enhancing and T2 lesions on magnetic resonance imaging compared with a control group of patients who did not receive this intervention, a new study has found.
The findings point to an anti-inflammatory effect of the therapy, said lead author David C. Mohr, PhD, professor of preventive medicine at Northwestern University Feinberg School of Medicine, Chicago, Illinois.
"This is the best evidence, the clearest evidence, we have that stress affects MS pathogenic processes," Dr. Mohr said.
The results are especially encouraging since study subjects had relatively active disease, he added. However, the benefits of the therapy were not sustained after the sessions stopped.
Their findings are published in the July 21 issue of Neurology.
Individual Sessions
The study included 121 adult patients at 3 US sites who had relapsing MS and evidence of clinical exacerbation of at least 1 gadolinium-enhancing (Gd+) brain lesion on imaging within the past 12 months.
These patients were randomly assigned to a group receiving stress management therapy or to a control group. All patients continued their disease-modifying therapy.
The stress management program involved 16 individual 50-minute sessions conducted over 20 to 24 weeks and led by a licensed PhD psychologist. The sessions were adapted to address specific concerns of patients with MS such as symptom and disability management.
Initial sessions focused on teaching problem-solving skills, relaxation, cognitive restructuring, and enhancement of social support. Among other modules, patients could choose from sessions on communication and assertiveness training, fatigue management, anxiety reduction, pain relief, and sexual dysfunction.
Patients in the control group received treatment as usual and participated in a day-long workshop after the 10th month.
The primary outcome was the cumulative number of Gd+ lesions during the active treatment period (weeks 8, 16, and 20). Secondary outcomes included the cumulative number of new and enlarging T2 lesions — a marker of more permanent brain lesions.
Investigators performed magnetic resonance imaging (MRI) of the brain at baseline and at weeks 8, 16, 24, 32, 40, and 48.
Of 60 participants assigned to the intervention, 50 (83.3%) were classified as treatment completers, defined as completing at least 12 sessions.
No New Lesions
The researchers found that significantly more participants in the treatment group remained free of Gd+ lesions during treatment. As well, significantly more of those getting the intervention remained free of new T2 lesions.
New Lesions With Stress Management vs Control Condition
Patients in the treatment group were, for the most part, very pleased with the stress management guidance they received, said Dr. Mohr. "We got satisfaction ratings that were overwhelmingly positive."
The results appear to support the hypothesis of an anti-inflammatory effect of the intervention. The mechanism of how the therapy may reduce the number of lesions could involve the glucocorticoid receptors on immune cells, according to the authors.
Although psychological stress is difficult to measure, research has shown a link between stress and MS progression and exacerbation. Dr. Mohr previously reported results of a study that showed a significant relationship between moderately stressful life events, characterized by conflict and disruptions in daily routine, and the appearance of new lesions on MRI 4 to 8 weeks after the event.
Stress probably doesn't actually cause the brain lesions, though, said Dr. Mohr. "I suspect that stress decreases a person's ability to regulate the inflammatory processes, and this leaves that person more vulnerable to new brain lesions down the road."
Benefit Not Sustained
The results of the current study were particularly encouraging because patients had shown clinical exacerbation or at least 1 new brain lesion in the previous year. "So these were people with clearly active disease," said Dr. Mohr.
However, benefits of therapy did not last; no significant between-group differences in cumulative Gd+ lesions or new T2 lesions were noted during the 24-week post-treatment follow-up period.
While patients learned new coping skills during the trial, for some reason they were unable to sustain these new behaviors, commented Dr. Mohr. "For most of us, changing our behavior is a difficult thing to sustain. Some people can, but many lapse back into old behaviors. And that's true not just for MS patients."
It may be that the actual social interaction nurtured during one-on-one therapy sessions — something that ends when the therapy does — contributes to the change in lesion status, said Dr. Mohr.
Or, it could be that the duration of the treatment — 24 weeks — is simply not long enough to instill enduring positive behaviors. "Extending the length of treatment might result in a more durable effect," but factors such as cost and availability, especially in smaller and more rural areas, may make it difficult for people to participate in longer-term therapy, said Dr. Mohr.
However, the sessions may not need to be delivered face to face. Another recent study on which Dr. Mohr was the lead author showed that there is no difference between care delivered in person and care provided over the telephone, at least in terms of improved depression symptoms, in a primary care setting. "I think that the medium through which care is delivered doesn't matter," said Dr. Mohr.
Experts are developing Web-based and mobile phone applications that may help sustain the benefits of stress management techniques off-site, he said. "If we can integrate these methodologies, they may eventually be able to extend care in cost-effective ways that support behavior changes."
Direct Evidence
For Christoph Heesen, MD, from the Department of Neurology at the University Medical Center in Hamburg, Germany, the study may represent the first direct evidence of a causal link between stress and inflammatory activity in MS patients. Dr. Heesen co-wrote an editorial accompanying the study.
However, in an interview with Medscape Medical News, Dr. Heesen said the study raised some "pressing" issues, including that the effect "was so rapidly diminished after cessation of counseling sessions."
A possible explanation for this, he said, is that active support and bonding are necessary to gain benefits from counseling. "Meeting a person once a week, being attached to someone, having a continued follow-up, and just having a person listen to you, might be the beneficial effect."
If it was just the psychological technique used in the intervention that was the critical element, "one would have assumed at least some longer-lasting effect," said Dr. Heesen. He added that previous psychotherapy literature has suggested that such techniques are less important than the "social connectivity" in the relationship established between client and therapist.
The problem, though, is that "we won’t be able to give every MS patient in the world a personal coach or a person who will talk to him once a week for the next 20 years."
But it might not be necessary to have trained and experienced psychologists providing the support; perhaps it's enough to have a good friend or an MS nurse provide a sympathetic ear, said Dr. Heesen.
And he agreed that ongoing social support could be provided using tools such as Web- and telephone-based applications.
Dr. Heesen noted that two thirds of eligible patients did not meet inclusion criteria for the study (362 of the 777 initially screened), which casts doubt on the applicability of such interventions to the general MS population.
"One needs to always be cautious if only a small number of people get into a trial. In this case, it might be that the intervention only works in highly inflammatory cases."
As well, the significant number of patients who fulfilled entry criteria but declined to participate (205 of those screened) points to the fact that many MS patients, especially early in their diagnosis, are too busy with their careers and family life to devote half a year of their life to once-a-week counseling sessions at an MS center.
The study was supported by the National Institute of Child Health & Human Development. Dr. Mohr receives research funding from the NIH. For conflict of interest information for other study authors, see original paper. Drs. Christoph Heesen and Stefan M. Gold report no financial relationships relevant to the manuscript.
Neurology 2012;79:412-419, 398-399. Abstract Editorial
July 11, 2012 — Multiple sclerosis (MS) patients who completed a course of behavioral stress management had fewer new gadolinium-enhancing and T2 lesions on magnetic resonance imaging compared with a control group of patients who did not receive this intervention, a new study has found.
The findings point to an anti-inflammatory effect of the therapy, said lead author David C. Mohr, PhD, professor of preventive medicine at Northwestern University Feinberg School of Medicine, Chicago, Illinois.
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Dr. David C. Mohr |
"This is the best evidence, the clearest evidence, we have that stress affects MS pathogenic processes," Dr. Mohr said.
The results are especially encouraging since study subjects had relatively active disease, he added. However, the benefits of the therapy were not sustained after the sessions stopped.
Their findings are published in the July 21 issue of Neurology.
Individual Sessions
The study included 121 adult patients at 3 US sites who had relapsing MS and evidence of clinical exacerbation of at least 1 gadolinium-enhancing (Gd+) brain lesion on imaging within the past 12 months.
These patients were randomly assigned to a group receiving stress management therapy or to a control group. All patients continued their disease-modifying therapy.
The stress management program involved 16 individual 50-minute sessions conducted over 20 to 24 weeks and led by a licensed PhD psychologist. The sessions were adapted to address specific concerns of patients with MS such as symptom and disability management.
Initial sessions focused on teaching problem-solving skills, relaxation, cognitive restructuring, and enhancement of social support. Among other modules, patients could choose from sessions on communication and assertiveness training, fatigue management, anxiety reduction, pain relief, and sexual dysfunction.
Patients in the control group received treatment as usual and participated in a day-long workshop after the 10th month.
The primary outcome was the cumulative number of Gd+ lesions during the active treatment period (weeks 8, 16, and 20). Secondary outcomes included the cumulative number of new and enlarging T2 lesions — a marker of more permanent brain lesions.
Investigators performed magnetic resonance imaging (MRI) of the brain at baseline and at weeks 8, 16, 24, 32, 40, and 48.
Of 60 participants assigned to the intervention, 50 (83.3%) were classified as treatment completers, defined as completing at least 12 sessions.
No New Lesions
The researchers found that significantly more participants in the treatment group remained free of Gd+ lesions during treatment. As well, significantly more of those getting the intervention remained free of new T2 lesions.
New Lesions With Stress Management vs Control Condition
| Endpoint | Treatment | Control | Odds Ratio (95% confidence interval) | P Value |
| Free of GD+ lesions | 76.8 | 54.7 | 2.77 (1.17 - 6.55) | .02 |
| Free of new T2 lesions | 69.5 | 42.7 | 3.07 (1.38 - 6.81) | .006 |
Patients in the treatment group were, for the most part, very pleased with the stress management guidance they received, said Dr. Mohr. "We got satisfaction ratings that were overwhelmingly positive."
The results appear to support the hypothesis of an anti-inflammatory effect of the intervention. The mechanism of how the therapy may reduce the number of lesions could involve the glucocorticoid receptors on immune cells, according to the authors.
Although psychological stress is difficult to measure, research has shown a link between stress and MS progression and exacerbation. Dr. Mohr previously reported results of a study that showed a significant relationship between moderately stressful life events, characterized by conflict and disruptions in daily routine, and the appearance of new lesions on MRI 4 to 8 weeks after the event.
Stress probably doesn't actually cause the brain lesions, though, said Dr. Mohr. "I suspect that stress decreases a person's ability to regulate the inflammatory processes, and this leaves that person more vulnerable to new brain lesions down the road."
Benefit Not Sustained
The results of the current study were particularly encouraging because patients had shown clinical exacerbation or at least 1 new brain lesion in the previous year. "So these were people with clearly active disease," said Dr. Mohr.
However, benefits of therapy did not last; no significant between-group differences in cumulative Gd+ lesions or new T2 lesions were noted during the 24-week post-treatment follow-up period.
While patients learned new coping skills during the trial, for some reason they were unable to sustain these new behaviors, commented Dr. Mohr. "For most of us, changing our behavior is a difficult thing to sustain. Some people can, but many lapse back into old behaviors. And that's true not just for MS patients."
It may be that the actual social interaction nurtured during one-on-one therapy sessions — something that ends when the therapy does — contributes to the change in lesion status, said Dr. Mohr.
Or, it could be that the duration of the treatment — 24 weeks — is simply not long enough to instill enduring positive behaviors. "Extending the length of treatment might result in a more durable effect," but factors such as cost and availability, especially in smaller and more rural areas, may make it difficult for people to participate in longer-term therapy, said Dr. Mohr.
However, the sessions may not need to be delivered face to face. Another recent study on which Dr. Mohr was the lead author showed that there is no difference between care delivered in person and care provided over the telephone, at least in terms of improved depression symptoms, in a primary care setting. "I think that the medium through which care is delivered doesn't matter," said Dr. Mohr.
Experts are developing Web-based and mobile phone applications that may help sustain the benefits of stress management techniques off-site, he said. "If we can integrate these methodologies, they may eventually be able to extend care in cost-effective ways that support behavior changes."
Direct Evidence
For Christoph Heesen, MD, from the Department of Neurology at the University Medical Center in Hamburg, Germany, the study may represent the first direct evidence of a causal link between stress and inflammatory activity in MS patients. Dr. Heesen co-wrote an editorial accompanying the study.
However, in an interview with Medscape Medical News, Dr. Heesen said the study raised some "pressing" issues, including that the effect "was so rapidly diminished after cessation of counseling sessions."
A possible explanation for this, he said, is that active support and bonding are necessary to gain benefits from counseling. "Meeting a person once a week, being attached to someone, having a continued follow-up, and just having a person listen to you, might be the beneficial effect."
If it was just the psychological technique used in the intervention that was the critical element, "one would have assumed at least some longer-lasting effect," said Dr. Heesen. He added that previous psychotherapy literature has suggested that such techniques are less important than the "social connectivity" in the relationship established between client and therapist.
The problem, though, is that "we won’t be able to give every MS patient in the world a personal coach or a person who will talk to him once a week for the next 20 years."
But it might not be necessary to have trained and experienced psychologists providing the support; perhaps it's enough to have a good friend or an MS nurse provide a sympathetic ear, said Dr. Heesen.
And he agreed that ongoing social support could be provided using tools such as Web- and telephone-based applications.
Dr. Heesen noted that two thirds of eligible patients did not meet inclusion criteria for the study (362 of the 777 initially screened), which casts doubt on the applicability of such interventions to the general MS population.
"One needs to always be cautious if only a small number of people get into a trial. In this case, it might be that the intervention only works in highly inflammatory cases."
As well, the significant number of patients who fulfilled entry criteria but declined to participate (205 of those screened) points to the fact that many MS patients, especially early in their diagnosis, are too busy with their careers and family life to devote half a year of their life to once-a-week counseling sessions at an MS center.
The study was supported by the National Institute of Child Health & Human Development. Dr. Mohr receives research funding from the NIH. For conflict of interest information for other study authors, see original paper. Drs. Christoph Heesen and Stefan M. Gold report no financial relationships relevant to the manuscript.
Neurology 2012;79:412-419, 398-399. Abstract Editorial
