case-control study – American ME and CFS Society

People with Long Covid and ME/CFS Exhibit Similarly Impaired Dexterity and Bimanual Coordination: A Case-Case-Control Study

Abstract:

Purpose: Dexterity and bimanual coordination had not previously been compared between people with long COVID and people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Therefore, this study determined dexterity and bimanual coordination in people with long COVID (∼16 month illness duration; n=21) and ME/CFS (∼16 year illness duration; n=20), versus age-matched healthy controls (n=20).

Methods: Dexterity, and bimanual coordination was determined using the Purdue pegboard test.

Results: The main findings of the present investigation were that people with ME/CFS and people with long COVID were generally comparable for Purdue pegboard tests (p>0.556 and d<0.36 for pairwise comparisons). It is worth noting however, that both these patient groups performed poorer in the Perdue pegboard test than healthy controls (p<0.169 and d>0.40 for pairwise comparisons).

Conclusions: These data suggest that both people with long COVID and people with ME/CFS have similarly impaired dexterity, and bimanual coordination. Therefore, there is an urgent need for interventions to target dexterity and bimanual coordination in people with ME/CFS, and given the current pandemic, people with long COVID.

Source: Sanal-Hayes NEM, Hayes LD, Mclaughlin M, Berry ECJ, Sculthorpe NF. People with Long Covid and ME/CFS Exhibit Similarly Impaired Dexterity and Bimanual Coordination: A Case-Case-Control Study. Am J Med. 2024 Feb 23:S0002-9343(24)00091-3. doi: 10.1016/j.amjmed.2024.02.003. Epub ahead of print. PMID: 38403179. https://www.amjmed.com/article/S0002-9343(24)00091-3/fulltext (Full text)

Neuroinflammation After COVID-19 With Persistent Depressive and Cognitive Symptoms

Abstract:

Importance: Persistent depressive symptoms, often accompanied by cognitive symptoms, commonly occur after COVID-19 illness (hereinafter termed COVID-DC, DC for depressive and/or cognitive symptoms). In patients with COVID-DC, gliosis, an inflammatory change, was suspected, but measurements of gliosis had not been studied in the brain for this condition.

Objective: To determine whether translocator protein total distribution volume (TSPO VT), a marker of gliosis that is quantifiable with positron emission tomography (PET), is elevated in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus of persons with COVID-DC.

Design, setting, and participants: This case-control study conducted at a tertiary care psychiatric hospital in Canada from April 1, 2021, to June 30, 2022, compared TSPO VT of specific brain regions in 20 participants with COVID-DC with that in 20 healthy controls. The TSPO VT was measured with fluorine F 18-labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([18F]FEPPA) PET.

Main outcomes and measures: The TSPO VT was measured in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus. Symptoms were measured with neuropsychological and psychological tests, prioritizing outcomes related to striatal function.

Results: The study population included 40 participants (mean [SD] age, 32.9 [12.3] years). The TSPO VT across the regions of interest was greater in persons with COVID-DC (mean [SD] age, 32.7 [11.4] years; 12 [60%] women) compared with healthy control participants (mean [SD] age, 33.3 [13.9] years; 11 [55%] women): mean (SD) difference, 1.51 (4.47); 95% CI, 0.04-2.98; 1.51 divided by 9.20 (17%). The difference was most prominent in the ventral striatum (mean [SD] difference, 1.97 [4.88]; 95% CI, 0.36-3.58; 1.97 divided by 8.87 [22%]) and dorsal putamen (mean difference, 1.70 [4.25]; 95% CI, 0.34-3.06; 1.70 divided by 8.37 [20%]). Motor speed on the finger-tapping test negatively correlated with dorsal putamen TSPO VT (r, -0.53; 95% CI, -0.79 to -0.09), and the 10 persons with the slowest speed among those with COVID-DC had higher dorsal putamen TSPO VT than healthy persons by 2.3 (2.30 divided by 8.37 [27%]; SD, 2.46; 95% CI, 0.92-3.68).

Conclusions and relevance: In this case-control study, TSPO VT was higher in patients with COVID-DC. Greater TSPO VT is evidence for an inflammatory change of elevated gliosis in the brain of an individual with COVID-DC. Gliosis may be consequent to inflammation, injury, or both, particularly in the ventral striatum and dorsal putamen, which may explain some persistent depressive and cognitive symptoms, including slowed motor speed, low motivation or energy, and anhedonia, after initially mild to moderate COVID-19 illness.

Source: Braga J, Lepra M, Kish SJ, Rusjan PM, Nasser Z, Verhoeff N, Vasdev N, Bagby M, Boileau I, Husain MI, Kolla N, Garcia A, Chao T, Mizrahi R, Faiz K, Vieira EL, Meyer JH. Neuroinflammation After COVID-19 With Persistent Depressive and Cognitive Symptoms. JAMA Psychiatry. 2023 May 31:e231321. doi: 10.1001/jamapsychiatry.2023.1321. Epub ahead of print. PMID: 37256580; PMCID: PMC10233457. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10233457/ (Full text)

Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study

Abstract:

BACKGROUND: The long term adverse effects of Severe Acute Respiratory Syndrome (SARS), a viral disease, are poorly understood.

METHODS: Sleep physiology, somatic and mood symptoms of 22 Toronto subjects, 21 of whom were healthcare workers, (19 females, 3 males, mean age 46.29 yrs.+/- 11.02) who remained unable to return to their former occupation (mean 19.8 months, range: 13 to 36 months following SARS) were compared to 7 healthy female subjects. Because of their clinical similarities to patients with fibromyalgia syndrome (FMS) these post-SARS subjects were similarly compared to 21 drug free female patients, (mean age 42.4 +/- 11.8 yrs.) who fulfilled criteria for fibromyalgia.

RESULTS: Chronic post-SARS is characterized by persistent fatigue, diffuse myalgia, weakness, depression, and nonrestorative sleep with associated REM-related apneas/hypopneas, an elevated sleep EEG cyclical alternating pattern, and alpha EEG sleep anomaly. Post- SARS patients had symptoms of pre and post-sleep fatigue and post sleep sleepiness that were similar to the symptoms of patients with FMS, and similar to symptoms of patients with chronic fatigue syndrome. Both post-SARS and FMS groups had sleep instability as indicated by the high sleep EEG cyclical alternating pattern rate. The post-SARS group had a lower rating of the alpha EEG sleep anomaly as compared to the FMS patients. The post-SARS group also reported less pre-sleep and post-sleep musculoskeletal pain symptoms.

CONCLUSIONS: The clinical and sleep features of chronic post-SARS form a syndrome of chronic fatigue, pain, weakness, depression and sleep disturbance, which overlaps with the clinical and sleep features of FMS and chronic fatigue syndrome.

Source: Moldofsky H, Patcai J. Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study. BMC Neurol. 2011 Mar 24;11:37. doi: 10.1186/1471-2377-11-37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071317/ (Full article)

Gynecological history in chronic fatigue syndrome: a population-based case-control study

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) affects disproportionately more women than men, and the condition is more common at perimenopause. We examined gynecological history events as risk factors for CFS.

METHODS: In a case-control study from a randomly selected population sample from Wichita, Kansas, 36 women with CFS and 48 nonfatigued controls, of similar age, race, and body mass index (BMI), answered a structured gynecological history questionnaire.

RESULTS: CFS cases and controls had the same mean age (51 years) and age at menarche (12 years). Overall, a greater proportion of women with CFS than controls reported pelvic pain unrelated to menstruation (22.2% vs. 1.7%, p = 0.004), endometriosis (36.1% vs. 16.7, %, p = 0.046), and periods of amenorrhea (53.9 % vs. 46.2%, p = 0.06). Compared to controls, women in the CFS group had a higher mean number of pregnancies (2.8 vs 2.0, p = 0.05) and gynecological surgeries (1.8 vs. 1.1, p = 0.05). Similar proportions of the CFS (69.4%) and control (72.9%) groups were menopausal. Although menopausal women in the CFS and control groups had similar mean age (55.5 and 55.8, respectively), menopause occurred about 4.4 years earlier in the CFS group (41.7 years vs. 46.1 years, respectively, p = 0.11). Among menopausal women, 76% of the CFS group reported hysterectomy vs. 54.6% of controls (p = 0.09), and 56% of women with CFS reported oophorectomy vs. 34.3% of controls (p = 0.11).

CONCLUSIONS: The higher prevalence of gynecological conditions and gynecological surgeries in women with CFS highlights the importance of evaluating gynecological health in these patients and the need for more research to clarify the chronologic and the pathophysiological relationships between these conditions and CFS.

Source: Boneva RS, Maloney EM, Lin JM, Jones JF, Wieser F, Nater UM, Heim CM, Reeves WC. Gynecological history in chronic fatigue syndrome: a population-based case-control study. J Womens Health (Larchmt). 2011 Jan;20(1):21-8. doi: 10.1089/jwh.2009.1900. Epub 2010 Nov 20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017420/ (Full article)

Reduced heart rate variability predicts poor sleep quality in a case-control study of chronic fatigue syndrome

Abstract:

Parasympathetic function is important in the induction and maintenance of sleep. We examined whether nocturnal vagal modulation of heart rate is related to the poor sleep quality commonly reported in chronic fatigue syndrome (CFS).

Heart rate (HR, as R-R intervals) was continuously monitored during sleep in 20 patients with CFS and 20 matched control subjects. Questionnaires assessed demographic information, symptoms, functional impairment, and subjective sleep quality.

CFS was associated with more sleep problems in general and poorer subjective sleep quality on the study night (all p < 0.003), and reports of repeated awakening during the night were 7 times more likely compared to healthy subjects (p = 0.017). Time and frequency-domain parameters of HR variability during sleep were significantly lower in patients with CFS (all p < 0.006). Multiple regression analyses revealed that heart rate variability (HRV) parameters were the best predictors of subjective sleep measures.

This study identified significant reductions in vagal modulation of heart rate during sleep in CFS. Low HRV strongly predicted sleep quality-suggesting a pervasive state of nocturnal sympathetic hypervigilance in CFS.

Source: Burton AR, Rahman K, Kadota Y, Lloyd A, Vollmer-Conna U. Reduced heart rate variability predicts poor sleep quality in a case-control study of chronic fatigue syndrome. Exp Brain Res. 2010 Jul;204(1):71-8. doi: 10.1007/s00221-010-2296-1. Epub 2010 May 26. https://www.ncbi.nlm.nih.gov/pubmed/20502886

Nitric oxide metabolite production during exercise in chronic fatigue syndrome: a case-control study

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a disabling illness of unknown etiology that is characterized by fatigue associated with a reduced ability to work, lasting for more than 6 months, and accompanied by a specific set of symptoms. The diagnosis remains difficult because of the absence of laboratory tests and is, therefore, made largely on the basis of the symptoms reported by the patient. The aim of this study was to analyze differences in blood nitrate levels in CFS patients and a matched control group after a physical exercise test.

METHODS: Forty-four consecutive female patients with CFS and 25 healthy women performed an exercise test using a cycle ergometer with monitoring of cardiopulmonary response. Blood samples were obtained for biochemical analyses of glucose, lactate, and nitrates at the beginning (under resting conditions) and after the maximal and supramaximal tests.

RESULTS: Plasma nitrates differed between the groups, with higher values in the CFS group (F = 6.93, p = 0.003). Nitrate concentration increased in relation to workload and reached higher values in the CFS group, the maximum difference with respect to the control group being 295% (t = 4.88, p < 0.001).

CONCLUSIONS: The main result of the present study is that nitric oxide (NO) metabolites (nitrates) showed a much higher increase after a maximal physical test in CFS patients than in a group of matched subjects. This combination (exercise plus NO response evaluation) may be useful in the assessment of CFS.

Source: Suárez A, Guillamó E, Roig T, Blázquez A, Alegre J, Bermúdez J, Ventura JL, García-Quintana AM, Comella A, Segura R, Javierre C. Nitric oxide metabolite production during exercise in chronic fatigue syndrome: a case-control study. J Womens Health (Larchmt). 2010 Jun;19(6):1073-7. doi: 10.1089/jwh.2008.1255. https://www.ncbi.nlm.nih.gov/pubmed/20469961

Frequency of attendance in general practice and symptoms before development of chronic fatigue syndrome: a case-control study

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) research has concentrated on infective, immunological, and psychological causes. Illness behaviour has received less attention, with most research studying CFS patients after diagnosis. Our previous study on the records of an insurance company showed a highly significant increase in illness reporting before development of CFS.

AIM: To investigate the number and type of general practitioner (GP) consultations by patients with CFS for 15 years before they develop their condition.

DESIGN OF STUDY: Case-control study in 11 general practices in Devon.

SETTING: Forty-nine patients with CFS (satisfying the Centers for Disease Control criteria), 49 age, sex, and general practice matched controls, and 37 patients with multiple sclerosis (MS) were identified from the general practices’ computerised databases.

METHOD: The number of general practice consultations and symptoms recorded in three five-year periods (quinquennia) were counted before development of the patients’ condition.

RESULTS: The median number of consultations was significantly higher for CFS patients than that of matched controls in each of the quinquennia: ratios for first quinquennium = 1.88, P = 0.01; second quinquennium = 1.70, P = 0.005; last quinquennium = 2.25, P < 0.001. More CFS patients than controls attended for 13 of the 18 symptoms studied. Significant increases were found for upper respiratory tract infection (P < 0.001), lethargy (P < 0.001), and vertigo (P = 0.02). Similar results were found for CFS patients when compared with MS.

CONCLUSIONS: CFS patients consulted their GP more frequently in the 15 years before development of their condition, for a wide variety of complaints. Several possibilities may explain these findings. The results support the hypothesis that behavioural factors have a role in the aetiology of CFS.

Comment in:

Chronic fatigue syndrome. [Br J Gen Pract. 2001]

Source: Hamilton WT, Hall GH, Round AP. Frequency of attendance in general practice and symptoms before development of chronic fatigue syndrome: a case-control study. Br J Gen Pract. 2001 Jul;51(468):553-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1314047/ (Full article)

Human herpesviruses 6 and 7 in chronic fatigue syndrome: a case-control study

Abstract:

We conducted this study to determine whether infection with human herpesvirus (HHV) 6A, HHV-6B, or HHV-7 differed between patients with chronic fatigue syndrome and control subjects. We recruited 26 patients and 52 nonfatigued matched control subjects from Atlanta.

Serum samples were tested by enzyme immunoassay for seroreactivity to HHV-6, and all were seropositive. Lymphocyte specimens were cocultivated with cord blood lymphocytes and assayed for HHV-6 and HHV-7; neither virus was isolated. Finally, lymphocytes were tested by use of 3 polymerase chain reaction methods for HHV-6A, HHV-6B, and HHV-7 DNA. HHV-6A or HHV-6B DNA was detected in 17 (22.4%) of 76 samples, and there were no significant differences (by matched analyses) between patients (3 [11.5%] of 26) and control subjects (14 [28%] of 50).

HHV-7 DNA was detected in 14 subjects, and although control subjects (12 [24%]) were more likely than patients (2 [7.7%]) to be positive, the difference was not statistically significant. We found no evidence that active or latent infection with HHV-6A, HHV-6B, HHV-7, or any combination these 3 HHVs is associated with chronic fatigue syndrome.

Source: Reeves WC, Stamey FR, Black JB, Mawle AC, Stewart JA, Pellett PE. Human herpesviruses 6 and 7 in chronic fatigue syndrome: a case-control study. Clin Infect Dis. 2000 Jul;31(1):48-52. Epub 2000 Jul 24. http://www.ncbi.nlm.nih.gov/pubmed/10913395

Chronic fatigue syndrome in private practice psychiatry: family history of physical and mental health

Abstract:

Forty-five psychiatric patients with chronic fatigue syndrome (CFS) were compared, using the case-control method, to two control groups selected from the same practice and matched on age, gender, and psychiatric diagnosis.

The first control group (C-I, N=90) was selected on the basis of relatively good physical health. The second control group (C-II, N=45) was selected without regard to physical health. The reported family history of physical health revealed: the CFS mothers died at a younger age than the C-II mothers; both parents died before age 65 among the CFS parents more frequently than did the C-I parents; and the CFS parents had an increased prevalence of cancer, autoimmune disorders, and CFS-like conditions as compared to the families of one or both control groups.

The reported family history of mental disorders revealed no significant differences in any of these conditions between the CFS patients and either control group.

Source: Endicott NA. Chronic fatigue syndrome in private practice psychiatry: family history of physical and mental health. J Psychosom Res. 1999 Oct;47(4):343-54. http://www.ncbi.nlm.nih.gov/pubmed/10616228

Psychological symptoms in chronic fatigue and juvenile rheumatoid arthritis

Abstract:

OBJECTIVE: To determine if psychological morbidity in youth with chronic fatigue is caused by the stress of coping with a chronic illness.

STUDY DESIGN: Case-control study comparing pediatric patients with debilitating chronic fatigue and matched subjects with juvenile rheumatoid arthritis, a chronic medical illness with similar functional sequelae.

SETTING: Pediatric Infectious Diseases Clinic and Juvenile Rheumatoid Arthritis Clinic of Kosair Children’s Hospital.

PARTICIPANTS: Nineteen children and adolescents with debilitating chronic fatigue and 19 age- and sex-matched peers with juvenile rheumatoid arthritis. Outcome. Structured Interview, Kaufman Brief Intelligence Test, Child Behavior Checklist, and Youth Self-Report.

RESULTS: Intellectual functioning on the Kaufman Brief Intelligence Test Composite was average (103, standard score) for both groups. Pediatric patients with chronic fatigue had higher levels of internalizing psychological distress than patients suffering from juvenile rheumatoid arthritis, despite the fact that both groups had a similar pattern of decline in social and physical activities. Duration of illness did not explain the difference in psychological symptoms.

CONCLUSIONS: Psychological factors may play a more active role in debilitating chronic fatigue in pediatric patients than can be explained by the stress of coping with a similar chronic, non-life-threatening illness.

Source: Carter BD, Kronenberger WG, Edwards JF, Marshall GS, Schikler KN, Causey DL. Psychological symptoms in chronic fatigue and juvenile rheumatoid arthritis. Pediatrics. 1999 May;103(5 Pt 1):975-9. http://www.ncbi.nlm.nih.gov/pubmed/10224175