Post-exertional malaise in veterans with gulf war illness, 2019, Lindheimer Cook et al

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https://www.sciencedirect.com/science/article/abs/pii/S0167876019305495

International Journal of Psychophysiology
Available online 28 November 2019
In Press, Journal Pre-proof


Post-exertional malaise in veterans with gulf war illness
Author links open overlay panel
Jacob B.Lindheimerab
Aaron J.Stegnerab
Glenn C.Wyliecd
Jacquelyn C.Klein-Adamsc
Neda E.Almassiab
Jacob V.Ninnemanab
Stephanie M.VanRiperab
Ryan J.Doughertyb
Michael J.Falvoce1
Dane B.Cookab
1
a
William S. Middleton Memorial Veterans Hospital, 2500 Overlook Terrace, Madison, WI 53705, United States of America
b
Department of Kinesiology, University of Wisconsin-Madison, 2000 Observatory Dr, Madison, WI 53706, United States of America
c
War Related Illness and Injury Study Center, Department of Veterans Affairs New Jersey Health Care System, 385 Tremont Ave, East Orange, NJ 07018, United States of America
d
Kessler Foundation, 1199 Pleasant Valley Way, West Orange, NJ 07052, United States of America
e
New Jersey Medical School, Rutgers Biomedical and Health Sciences, 185 S Orange Ave, Newark, NJ 07103, United States of America
Received 7 May 2019, Revised 7 October 2019, Accepted 11 November 2019, Available online 28 November 2019.

https://doi.org/10.1016/j.ijpsycho.2019.11.008Get rights and content

Highlights


•
Studies of post-exertional malaise that involve Veterans with Gulf War (GWI) Illness rarely measure potential changes in symptoms

•
We examined the effect of acute aerobic exercise on mood, fatigue, and other GWI related symptoms in 39 Veterans with GWI and 28 health control Veterans

•
In the full sample, we did not observe differences between groups in terms of post-exertional exacerbation of symptoms

•
When the GWI group was restricted only to Veterans who endorsed feeling unwell following exercise or physical exertion during baseline testing, Veterans with GWI displayed a larger exacerbation of symptoms than healthy controls



Abstract
Post-exertional malaise (PEM) is a potentially debilitating aspect of Gulf War Illness (GWI) that has received limited research attention.

The purpose of the present investigation was to determine symptom severity changes following exercise in Veterans with GWI compared to control Veterans without GWI (CO).

Sixty-seven Veterans (n = 39 GWI; n = 28 CO) underwent a 30-minute submaximal exercise challenge at 70% of heart rate reserve.

Symptom measurements (e.g. fatigue, pain) occurred pre-, immediately post-, and 24-hour post-exercise.

Self-reported physical and mental health, and physiological and perceptual responses to exercise were compared between groups using descriptive statistics, independent samples t-tests and repeated measures Analysis of Variance (RM-ANOVA).

Post-exertional malaise was modeled using Group by Time (2 × 3) doubly-multivariate, RM-MANOVAs for (1) mood, (2) pain and (3) GWI-related symptoms, respectively (α = 0.05). Data were analyzed for the full sample of Veterans with GWI (n = 39) compared to CO (n = 28) and a subsample of Veterans (n = 18) who endorsed “feeling unwell after physical exercise or exertion” (“PEM endorsers”) during screening.

Veterans with GWI reported significantly lower physical and mental health.

Groups exercised at similar relative exercise intensities, but GWI perceived exercise as more painful and fatiguing.

Group-by-Time interactions were not significant for the entire sample for the three PEM models, however limiting the GWI sample to “PEM endorsers” resulted in significant interactions for Pain- and GWI-related PEM models.

These results indicate that not all GVs with GWI experience PEM 24 h after exercise, and that more research is needed to determine the extent that exercise worsens symptoms in GWI.

Keywords
Chronic disease
Cognition
Exercise
Fatigue
Pain
Persian Gulf War
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I have not read the paper yet, but it seems to me that this paper may just raise questions, not provide answers. GWI also does not have a definitive test. Is it really ME in these patients? Or is PEM not unique to ME? Or do these patients have both ME and GWI? Or is there yet another explanation?
 
strategist said:
Endorsing "feeling unwell after physical exercise or exertion" seems vague.
Click to expand...
Like calling migraines a slight headache with minor discomfort.

Poor definitions and reliance on dubious questionnaires does not help much to answer questions. I don't think it really ever was suggested PEM was notable in GWI other than comparisons to ME. "Endorsers" is weird typical "patient thinks" framing. It talks of perception of pain and fatigue but when the questions are aligned to fit with researchers' expectations it's always "fatigue was reduced". It's perception when it increases and it's real and significant when it decreases.

Not impressed. The researchers involved have a poor grasp of PEM and biased expectations.
 
Cook (one of the authors) did this study on ME/CFS in 2017.
—-
Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
Cook DB, et al. Brain Behav Immun. 2017.
Show full citation
Abstract
Post exertion malaise is one of the most debilitating aspects of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, yet the neurobiological consequences are largely unexplored. The objective of the study was to determine the neural consequences of acute exercise using functional brain imaging. Fifteen female Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients and 15 healthy female controls completed 30min of submaximal exercise (70% of peak heart rate) on a cycle ergometer. Symptom assessments (e.g. fatigue, pain, mood) and brain imaging data were collected one week prior to and 24h following exercise. Functional brain images were obtained during performance of: 1) a fatiguing cognitive task - the Paced Auditory Serial Addition Task, 2) a non-fatiguing cognitive task - simple number recognition, and 3) a non-fatiguing motor task - finger tapping. Symptom and exercise data were analyzed using independent samples t-tests. Cognitive performance data were analyzed using mixed-model analysis of variance with repeated measures. Brain responses to fatiguing and non-fatiguing tasks were analyzed using linear mixed effects with cluster-wise (101-voxels) alpha of 0.05. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients reported large symptom changes compared to controls (effect size ≥0.8, p<0.05). Patients and controls had similar physiological responses to exercise (p>0.05). However, patients exercised at significantly lower Watts and reported greater exertion and leg muscle pain (p<0.05). For cognitive performance, a significant Group by Time interaction (p<0.05), demonstrated pre- to post-exercise improvements for controls and worsening for patients. Brain responses to finger tapping did not differ between groups at either time point. During number recognition, controls exhibited greater brain activity (p<0.05) in the posterior cingulate cortex, but only for the pre-exercise scan. For the Paced Serial Auditory Addition Task, there was a significant Group by Time interaction (p<0.05) with patients exhibiting increased brain activity from pre- to post-exercise compared to controls bilaterally for inferior and superior parietal and cingulate cortices. Changes in brain activity were significantly related to symptoms for patients (p<0.05). Acute exercise exacerbated symptoms, impaired cognitive performance and affected brain function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients. These converging results, linking symptom exacerbation with brain function, provide objective evidence of the detrimental neurophysiological effects of post-exertion malaise.

Published by Elsevier Inc.
PMID
28216087 [Indexed for MEDLINE]
 
I don't think they are distinguishing post exertional fatigue from post exertional malaise. I have thought about this and I experience problems immediately with exercise beyond my limits which seems to e what they are looking at here, but the true unique post exertional malaise of ME is delayed and prolonged.

I just rarely get the fatigue part because I pace myself and know my limits. PEM creeps up on me :)
 
Easier to read abstract
Highlights

• Studies of post-exertional malaise that involve Veterans with Gulf War (GWI) Illness rarely measure potential changes in symptoms
• We examined the effect of acute aerobic exercise on mood, fatigue, and other GWI related symptoms in 39 Veterans with GWI and 28 health control Veterans
• In the full sample, we did not observe differences between groups in terms of post-exertional exacerbation of symptoms
• When the GWI group was restricted only to Veterans who endorsed feeling unwell following exercise or physical exertion during baseline testing, Veterans with GWI displayed a larger exacerbation of symptoms than healthy controls

Abstract
Post-exertional malaise (PEM) is a potentially debilitating aspect of Gulf War Illness (GWI) that has received limited research attention. The purpose of the present investigation was to determine symptom severity changes following exercise in Veterans with GWI compared to control Veterans without GWI (CO). Sixty-seven Veterans (n = 39 GWI; n = 28 CO) underwent a 30-minute submaximal exercise challenge at 70% of heart rate reserve. Symptom measurements (e.g. fatigue, pain) occurred pre-, immediately post-, and 24-hour post-exercise.

Self-reported physical and mental health, and physiological and perceptual responses to exercise were compared between groups using descriptive statistics, independent samples t-tests and repeated measures Analysis of Variance (RM-ANOVA). Post-exertional malaise was modeled using Group by Time (2 × 3) doubly-multivariate, RM-MANOVAs for (1) mood, (2) pain and (3) GWI-related symptoms, respectively (α = 0.05). Data were analyzed for the full sample of Veterans with GWI (n = 39) compared to CO (n = 28) and a subsample of Veterans (n = 18) who endorsed “feeling unwell after physical exercise or exertion” (“PEM endorsers”) during screening. Veterans with GWI reported significantly lower physical and mental health.

Groups exercised at similar relative exercise intensities, but GWI perceived exercise as more painful and fatiguing. Group-by-Time interactions were not significant for the entire sample for the three PEM models, however limiting the GWI sample to “PEM endorsers” resulted in significant interactions for Pain- and GWI-related PEM models. These results indicate that not all GVs with GWI experience PEM 24 h after exercise, and that more research is needed to determine the extent that exercise worsens symptoms in GWI.
Click to expand...

Scihub link, https://sci-hub.se/10.1016/j.ijpsycho.2019.11.008

Conclusion

Cross-sectional, epidemiological, and clinical trial data make clear that GVs with GWI suffer numerous symptoms and conditions that defy medical explanation and result in profound reduction in quality of life. It is also clear from these studies that a significant percentage of GVs report feeling unwell following exercise or physical exertion. However, the exact nature, severity, and time-course of PEM in GWI is unknown and to our knowledge has not been tested in controlled laboratory settings. We report here that symptom exacerbation in response to an acute submaximal aerobic exercise challenge did not occur in all GVs with GWI either immediately- or 24-hr post-exercise. This appears to be due, in part, to the majority of our sample not endorsing symptom worsening with exertion. More PEM research that systematically determines the mode, intensity, and duration of exercise that are tolerable (i.e. do not produce PEM) and necessary (i.e. produce clear PEM) is needed to better understand this phenomenon in this population. Future investigations should also be aimed toward further exploring the difference between those GWV who do and do not exhibit PEM. We show here that acute exercise does not bring about a significant worsening of symptom severity for the majority of GVs that were tested.
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alex3619 said:
I have not read the paper yet, but it seems to me that this paper may just raise questions, not provide answers. GWI also does not have a definitive test. Is it really ME in these patients? Or is PEM not unique to ME? Or do these patients have both ME and GWI? Or is there yet another explanation?
Click to expand...
Your questions seem particularly pertinent in view of this sentence in the conclusions:
We show here that acute exercise does not bring about a significant worsening of symptom severity for the majority of GVs that were tested.
Click to expand...
Impressions after a quick skim only:
They do seem to understand PEM in ME.
They are very vague in their definition of PEM in GWI.
PEM, even by their vague definition, is much less of an issue in GWI in this study than in ME - which to my mind does raise the question do the minority who do have PEM really have ME (instead or as well as)?
The authors call for a better definition and operationalisation of PEM. Yes to that.
 
Seems interesting.

Less than half of patients with gulf war illness agreed with the statement "feeling unwell after physical exercise or exertion". And there were no group by time difference in symptoms after the exercise test for the whole sample. That would seem to suggest a difference with ME/CFS. The paper writes: "In the present study, PEM responses were clearly not as robust as seen in the ME/CFS literature." It seems that the authors had not expected this result.
 
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