Cognitive assessment in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a cognitive substudy of the multi-site clinical assessment of ME/CFS (MCAM)

Abstract:

Introduction: Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) experience cognitive problems with attention, information processing speed, working memory, learning efficiency, and executive function. Commonly, patients report worsening of cognitive symptoms over time after physical and/or cognitive challenges. To determine, monitor, and manage longitudinal decrements in cognitive function after such exposures, it is important to be able to screen for cognitive dysfunction and changes over time in clinic and also remotely at home. The primary objectives of this paper were: (1) to determine whether a brief computerized cognitive screening battery will detect differences in cognitive function between ME/CFS and Healthy Controls (HC), (2) to monitor the impact of a full-day study visit on cognitive function over time, and (3) to evaluate the impact of exercise testing on cognitive dysfunction.

Methods: This cognitive sub-study was conducted between 2013 and 2019 across seven U.S. ME/CFS clinics as part of the Multi-Site Clinical Assessment of ME/CFS (MCAM) study. The analysis included 426 participants (261 ME/CFS and 165 HC), who completed cognitive assessments including a computerized CogState Brief Screening Battery (CBSB) administered across five timepoints (T0-T4) at the start of and following a full day in-clinic visit that included exercise testing for a subset of participants (182 ME/CFS and 160 HC). Exercise testing consisted of ramped cycle ergometry to volitional exhaustion. The primary outcomes are performance accuracy and latency (performance speed) on the computerized CBSB administered online in clinic (T0 and T1) and at home (T2-T4).

Results: No difference was found in performance accuracy between ME/CFS and HCs whereas information processing speed was significantly slower for ME/CFS at most timepoints with Cohen’s d effect sizes ranging from 0.3-0.5 (p < 0.01). The cognitive decline over time on all CBSB tasks was similar for patients with ME/CFS independent of whether exercise testing was included in the clinic visit.

Conclusion: The challenges of a clinic visit (including cognitive testing) can lead to further cognitive deficits. A single short session of intense exercise does not further reduce speed of performance on any CBSB tasks.

Source: Lange G, Lin JS, Chen Y, Fall EA, Peterson DL, Bateman L, Lapp C, Podell RN, Natelson BH, Kogelnik AM, Klimas NG, Unger ER. Cognitive assessment in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a cognitive substudy of the multi-site clinical assessment of ME/CFS (MCAM). Front Neurosci. 2024 Nov 1;18:1460157. doi: 10.3389/fnins.2024.1460157. PMID: 39554847; PMCID: PMC11565701. https://pmc.ncbi.nlm.nih.gov/articles/PMC11565701/ (Full text)

Chronic Overlapping Pain Conditions in people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a sample from the Multi-site Clinical Assessment of ME/CFS (MCAM) study

Abstract:

Background: Chronic overlapping pain conditions (COPCs), pain-related conditions that frequently occur together, may occur in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and could impact illness severity. This study aimed to identify comorbid COPCs in patients with ME/CFS and evaluate their impact on illness severity.

Methods: We used data from 923 participants in the Multi-Site Clinical Assessment of ME/CFS study, conducted in seven U.S. specialty clinics between 2012 and 2020, who completed the baseline assessment (595 ME/CFS and 328 healthy controls (HC)). COPCs included chronic low back pain (cLBP), chronic migraine/headache (cMHA), fibromyalgia (FM), interstitial cystitis/irritable bladder (IC/IB), irritable bowel syndrome (IBS), temporomandibular disorder (TMD). Illness severity was assessed through questionnaires measuring symptoms and functioning. Multivariate analysis of variance and analysis of covariance models were used for analyses. Log-binomial regression analyses were used to compute prevalence of COPCs and prevalence ratios (PR) between groups with 95% confidence intervals. Both unadjusted and adjusted results with age and sex are presented.

Results: 76% of participants with ME/CFS had at least one COPCs compared to 17.4% of HC. Among ME/CFS participants, cMHA was most prevalent (48.1%), followed by FM (45.0%), cLBP (33.1%), and IBS (31.6%). All individual COPCs, except TMD, were significantly more frequent in females than males. The unadjusted PR (ME/CFS compared to HC) was highest for FM [147.74 (95% confidence interval (CI) = 20.83-1047.75], followed by cLBP [39.45 (12.73-122.27)], and IC/IB [13.78 (1.88-101.24)]. The significance and order did not change after age and sex adjustment. The COPC comorbidities of cLBP and FM each had a significant impact on most health measures, particularly in pain attributes (Cohen’s d effect size 0.8 or larger). While the impact of COPC comorbidities on non-pain attributes and quality of life measures was less pronounced than that on pain, statistically significant differences between ME/CFS participants with and without COPCs were still evident.

Conclusions: More than 75% of ME/CFS participants had one or more COPCs. Multiple COPCs further exacerbated illness severity, especially among females with ME/CFS. Assessment and management of COPCs may help improve the health and quality of life for patients with ME/CFS.

Source: Fall EA, Chen Y, Lin JS, Issa A, Brimmer DJ, Bateman L, Lapp CW, Podell RN, Natelson BH, Kogelnik AM, Klimas NG, Peterson DL, Unger ER; MCAM Study Group. Chronic Overlapping Pain Conditions in people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a sample from the Multi-site Clinical Assessment of ME/CFS (MCAM) study. BMC Neurol. 2024 Oct 18;24(1):399. doi: 10.1186/s12883-024-03872-0. PMID: 39425035; PMCID: PMC11488184. https://pmc.ncbi.nlm.nih.gov/articles/PMC11488184/ (Full text)

Natural killer cytotoxicity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a multi-site clinical assessment of ME/CFS (MCAM) sub-study

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by substantial reduction in function accompanied by profound unexplained fatigue not significantly relieved by rest, post-exertional malaise, and other symptoms. Reduced natural killer (NK) cell count and cytotoxicity has been investigated as a biomarker for ME/CFS, but few clinical laboratories offer the test and multi-site verification studies have not been conducted.

Methods: We determined NK cell counts and cytotoxicity in 174 (65%) ME/CFS, 86 (32%) healthy control (HC) and 10 (3.7%) participants with other fatigue associated conditions (ill control [IC]) from the Multi-Site Clinical Assessment of ME/CFS (MCAM) study using an assay validated for samples shipped overnight instead of testing on day of venipuncture.

Results: We found a large variation in percent cytotoxicity [mean and (IQR) for ME/CFS and HC respectively, 34.1% (IQR 22.4-44.3%) and 33.6% (IQR 22.9-43.7%)] and no statistically significant differences between patients with ME/CFS and HC (p-value = 0.79). Analysis stratified on illness domain measured with standardized questionnaires did not identify an association of NK cytotoxicity with domain scores. Among all participants, NK cytotoxicity was not associated with survey results of physical and mental well-being, or health factors such as history of infection, obesity, smoking, and co-morbid conditions.

Conclusion: These results indicate this assay is not ready for clinical implementation and studies are needed to further explore immune parameters that may be involved in the pathophysiology of ME/CFS.

Source: Querec TD, Lin JS, Chen Y, Helton B, Kogelnik AM, Klimas NG, Peterson DL, Bateman L, Lapp C, Podell RN, Natelson BH, Unger ER; MCAM Study Group. Natural killer cytotoxicity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a multi-site clinical assessment of ME/CFS (MCAM) sub-study. J Transl Med. 2023 Apr 3;21(1):242. doi: 10.1186/s12967-023-03958-2. PMID: 37013608. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03958-2 (Full text)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Essentials of diagnosis and management

Abstract:

Despite myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) affecting millions of people worldwide, many clinicians lack the knowledge to appropriately diagnose or manage ME/CFS. Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful. Consequently, up to 91% of patients in the United States remain undiagnosed, and those diagnosed often receive inappropriate treatment. These problems are of increasing importance because after acute COVID-19, a significant percentage of people remain ill for many months with an illness similar to ME/CFS.
In 2015, the US National Academy of Medicine published new evidence-based clinical diagnostic criteria that have been adopted by the US Centers for Disease Control and Prevention. Furthermore, the United States and other governments as well as major health care organizations have recently withdrawn graded exercise and cognitive-behavioral therapy as the treatment of choice for patients with ME/CFS. Recently, 21 clinicians specializing in ME/CFS convened to discuss best clinical practices for adults affected by ME/CFS.
This article summarizes their top recommendations for generalist and specialist health care providers based on recent scientific progress and decades of clinical experience. There are many steps that clinicians can take to improve the health, function, and quality of life of those with ME/CFS, including those in whom ME/CFS develops after COVID-19. Patients with a lingering illness that follows acute COVID-19 who do not fully meet criteria for ME/CFS may also benefit from these approaches.
Source: Lucinda Bateman, MD, Alison C. Bested, MD, Hector F. Bonilla, MD, Ilene S. Ruhoy, MD, PhD, Maria A. Vera-Nunez, MD, MSBI, Brayden P. Yellman, MD et al. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Essentials of Diagnosis and Management. Mayo Clinic Proceedings. Open Access. Published:August 25, 2021DOI:https://doi.org/10.1016/j.mayocp.2021.07.004 https://www.mayoclinicproceedings.org/article/S0025-6196(21)00513-9/fulltext (Full text)

Documenting disability in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

BACKGROUND: According to the 2015 National Academy of Medicine report, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) “is a serious, chronic, complex, and systemic disease that frequently and dramatically limits the activities of affected patients.” ME/CFS affects between 1 and 2.5 million Americans, leaving as many as 75% unable to work due to physical, cognitive and functional impairment. Unfortunately, many doctors and lawyers lack the knowledge of how to properly document an ME/CFS disability claim, leaving patients unable to access disability benefits.

OBJECTIVE: The goal of this article is to summarize the approaches used by experienced clinicians and lawyers in successful ME/CFS disability claims.

METHODS: The authors reviewed the types of US disability insurance programs and the evidence commonly required by these programs to demonstrate ME/CFS disability.

RESULTS: This article summarizes the range of methods used in successful US disability claims, which include documentation of the functional impact of post-exertional malaise and the use of methods that provide objective evidence of impairment.

CONCLUSIONS: Medical providers and lawyers can use these tested methods to obtain disability benefits for people with ME/CFS. Physical therapists, occupational therapists, and other specialists play an important role in providing objective evidence for ME/CFS disability claims.

Source: Podell, Richard, Dimmock, Mary E., and Comerford, Barbara B. ‘Documenting Disability in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)’. 1 Jan. 2020 : 339 – 352. https://content.iospress.com/articles/work/wor203178 (Full text)

Documenting Disability in Myalgic encephalomyelitis/chronic Fatigue Syndrome (ME/CFS)

Abstract:

Background: According to the 2015 National Academy of Medicine report, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) “is a serious, chronic, complex, and systemic disease that frequently and dramatically limits the activities of affected patients.” ME/CFS affects between 1 and 2.5 million Americans, leaving as many as 75% unable to work due to physical, cognitive and functional impairment. Unfortunately, many doctors and lawyers lack the knowledge of how to properly document an ME/CFS disability claim, leaving patients unable to access disability benefits.

Objective: The goal of this article is to summarize the approaches used by experienced clinicians and lawyers in successful ME/CFS disability claims.

Methods: The authors reviewed the types of US disability insurance programs and the evidence commonly required by these programs to demonstrate ME/CFS disability.

Results: This article summarizes the range of methods used in successful US disability claims, which include documentation of the functional impact of post-exertional malaise and the use of methods that provide objective evidence of impairment.

Conclusions: Medical providers and lawyers can use these tested methods to obtaining disability benefits for people with ME/CFS. Physical therapists, occupational therapists, and other specialists play an important role in providing objective evidence for ME/CFS disability claims.

Source: Podell R, Dimmock ME, Comerford BB. Documenting disability in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) [published online ahead of print, 2020 Jun 16]. Work. 2020;10.3233/WOR-203178. doi:10.3233/WOR-203178 https://pubmed.ncbi.nlm.nih.gov/32568153/