The Presentation of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Is Not Influenced by the Presence or Absence of Joint Hypermobility.

OBJECTIVE: To examine demographic and clinical characteristics of individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with and without joint hypermobility We hypothesized that patients who were joint hypermobility-positive would have an earlier onset of ME/CFS symptoms as well as increased severity, a greater number of comorbid conditions, and a lower health-related quality of life. STUDY DESIGN: From an observational cohort study of 55 individuals meeting the Fukuda criteria for ME/CFS, we compared groups using a Beighton score cutoff of 4 or higher to indicate joint hypermobility. Chart data were collected to examine the age and type of onset of ME/CFS and the presence of comorbid conditions. The impact on quality of life was assessed through questionnaires that included the Peds QL, Functional Disability Inventory, Peds QL Multidimensional Fatigue Scale, and Anxiety Subscale of the Symptom Checklist 90. RESULTS: There was no significant difference between groups in mean ± SD age at onset of ME/CFS (13.3 ± 3.3 years vs 13.3 ± 2.3 years; P = .92), sex, frequency, and severity of ME/CFS symptoms, orthostatic intolerance symptoms, or comorbid conditions. There was no significant difference between the groups in measures of health-related quality of life using a Beighton score cutoff of 4 or a cutoff of 5 to define joint hypermobility. CONCLUSIONS: Despite being a risk factor for the development of ME/CFS, joint hypermobility as defined in this study was not associated with other clinical characteristics of the illness.

Improvement of severe myalgic encephalomyelitis/chronic fatigue syndrome symptoms following surgical treatment of cervical spinal stenosis.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a potentially disabling disorder. Little is known about the contributors to severe forms of the illness. We describe three consecutive patients with severe ME/CFS whose symptoms improved after recognition and surgical management of their cervical spinal stenosis. METHODS: All patients satisfied clinical criteria for ME/CFS and orthostatic intolerance, and were later found to have cervical spinal stenosis. Overall function was assessed before and after surgery using the Karnofsky score and the SF-36 physical function subscale score. RESULTS: Neurological findings included > 3+ deep tendon reflexes in 2 of 3, a positive Hoffman sign in 2 of 3, tremor in 2 of 3, and absent gag reflex in 1 of 3. The cervical spine canal diameter in the three patients ranged from 6 to 8.5 mm. One had congenital cervical stenosis with superimposed spondylosis, and two had single- or two-level spondylosis. Anterior cervical disc replacement surgery in two patients and a hybrid anterior cervical disc fusion and disc replacement in the third was associated with a marked improvement in myelopathic symptoms, resolution of lightheadedness and hemodynamic dysfunction, improvement in activity levels, and improvement in global ME/CFS symptoms. CONCLUSIONS: The prompt post-surgical restoration of more normal function suggests that cervical spine stenosis contributed to the pathogenesis of refractory ME/CFS and orthostatic symptoms. The improvements following surgery emphasize the importance of a careful search for myelopathic examination findings in those with ME/CFS, especially when individuals with severe impairment are not responding to treatment.

Two-Year Follow-Up of Impaired Range of Motion in Chronic Fatigue Syndrome.

OBJECTIVE: To measure changes in range of motion (ROM) over time in a cohort of 55 adolescents and young adults with chronic fatigue syndrome and to determine whether changes in ROM correlated with changes in health-related quality of life. STUDY DESIGN: Participants underwent a standardized examination of 11 areas of limb and spine ROM at baseline and at 3- to 6-month intervals for 2 years, resulting in a ROM score that ranged from 0 (normal throughout) to 11 (abnormal ROM in all areas tested). We measured the time until the ROM score was ≤2 (the score in healthy age-matched controls). Change in ROM was measured by subtracting the 24-month from the baseline ROM score and by summing the degrees of change in the 10 tests with continuous outcomes. Health-related quality of life was measured using the Pediatric Quality of Life Inventory 4.0 (PedsQL). RESULTS: The mean age at enrollment was 16.5 years (range 10-23). Two-year follow-up was available for 53 (96%). The proportion with a ROM score of >2 fell gradually over 2 years, from 78% at entry to 20% at 24 months (P < .001). ROM scores improved from a median of 5 at entry to 2 at 24 months (P < .001). The change in the summed degrees of improvement in ROM correlated positively with improvement in the PedsQL physical function subscale (r = 0.30; P < .03). CONCLUSIONS: In association with multimodal therapy, young people with chronic fatigue syndrome experienced progressively less impairment in ROM over 2 years, correlating with improvements in the physical function subscale of the PedsQL.

Cow's milk protein intolerance in adolescents and young adults with chronic fatigue syndrome.

AIM: To examine the prevalence, clinical features and influence on illness severity of cow's milk protein intolerance in young people with chronic fatigue syndrome. METHODS: In a two-year prospective study of 55 adolescents and young adults with chronic fatigue syndrome, we defined intolerance to milk protein if subjects reported (i) no evidence of immediate or anaphylactic reactions to milk, (ii) at least 2 of the following 3 chronic symptoms: gastroesophageal reflux, early satiety and epigastric/abdominal pain, (iii) improvement in upper gastrointestinal symptoms on a milk protein elimination diet and (iv) at least 2 recurrences of upper gastrointestinal symptoms >two hours following open re-exposure to milk protein. Subjects completed three quality of life surveys at baseline and at six months. RESULTS: The mean (SD) age of the 55 participants was 16.5 (2.1) years. Seventeen (31%; 95% CI, 19-43%) met study criteria for cow's milk protein intolerance. Compared to milk-tolerant subjects, milk-sensitive participants had significantly worse health-related quality of life at baseline but not at six months (after institution of the milk-free diet). CONCLUSION: Cow's milk protein intolerance is a common problem in young people with chronic fatigue syndrome and is a treatable contributor to their symptoms.

Impaired range of motion of limbs and spine in chronic fatigue syndrome.

OBJECTIVE: To determine whether adolescents and young adults with chronic fatigue syndrome (CFS) have a greater prevalence of impaired range of motion (ROM) of the limbs and spine than healthy control patients. STUDY DESIGN: Case-control study comparing rates of abnormal ROM in 48 consecutive adolescents and young adults with CFS and 48 healthy control patients matched by sex and joint hypermobility. We examined range of ankle dorsiflexion, passive straight-leg raise, seated slump, upper-limb neurodynamic test, prone knee bend, and prone press-up. Abnormal ROM was defined before the study began. The number of abnormal responses ranged from 0 (normal ROM throughout) to 11 (impaired ROM in all areas tested). RESULTS: The median number of areas with impaired ROM was greater in patients with CFS at the onset of stretch in the involved limb (5 vs 2, P<.001) and at end-range (2 vs 0, P<.001). Patients with CFS were more likely to have greater than 3 areas of impaired ROM (OR 6.0, 95% CI 2.1-17.3; P<.001) and were more likely to develop abnormal symptomatic responses to the individual tests and to the overall assessment (40% vs 4%; P<.001). CONCLUSIONS: Impaired ROM is more common in subjects with CFS than in healthy adolescents and young adults matched by sex and joint hypermobility. Adding a longitudinal strain to the nerves and soft tissues provoked symptoms in some subjects with CFS. The causes, functional impact, and optimal treatment of these abnormalities warrant further study.

Impaired Health-Related Quality of Life in Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Impact of Core Symptoms.

Objective: The objectives of this study were to compare the health-related quality of life (HRQOL) of a North American population of adolescents and young adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to (1) healthy controls (HC), (2) adolescents with ME/CFS in other countries, and (3) other forms of pediatric chronic illness, and (4) to examine the influence of the core illness symptoms in the Institute of Medicine (IOM) case definition on impaired HRQOL. Study design: Cross-sectional study comparing individuals with ME/CFS referred to a tertiary care Chronic Fatigue clinic and HC. Eligible participants were age 10-30 years and met the Fukuda criteria for CFS. HC were eligible if they were age 10-30 years, with self-reported good, very good, or excellent general health. Pediatric HRQOL was measured using the PedsQL (Pediatric Quality of Life Inventory) and other validated instruments. Results: We enrolled 55 consecutive ME/CFS patients (46 F) aged 10-23 years. From a pool of 69 potential HC we selected 55 with similar age and gender distribution for comparison. The total and subscale scores on the PedsQL and on all other measures of HRQOL indicated significantly worse function among those with ME/CFS (all P < 0.001). The self-reported frequency of post-exertional malaise (PEM) was significantly associated with the severity of impaired HRQOL (P < 0.001). Cognitive impairment had a weaker association with the PedsQL score (P = 0.02). Orthostatic intolerance was present in 96% of the ME/CFS population. Of the 55 who satisfied the Fukuda criteria, 47 (85%) also satisfied the IOM criteria for the diagnosis. Those meeting the IOM criteria had worse PedsQL total scores than those meeting just the Fukuda criteria (P < 0.001). Conclusions: HRQOL was substantially lower in an ambulatory population of adolescents and young adults with ME/CFS than for healthy controls in North America, consistent with reports from other continents. HRQOL was also lower in ME/CFS than has been described in children with asthma, diabetes mellitus, epilepsy, eosinophilic gastroenteritis, and cystic fibrosis. The findings of this study lend further support to the inclusion of PEM, cognitive impairment, and orthostatic intolerance as core symptoms of pediatric ME/CFS.

Postural tachycardia syndrome and other forms of orthostatic intolerance in Ehlers-Danlos syndrome.

OBJECTIVE: To review the association between orthostatic intolerance syndromes and both joint hypermobility and Ehlers-Danlos syndrome, and to propose reasons for identifying hereditary connective tissue disorders in those with orthostatic intolerance in the context of both clinical care and research. METHODS: We searched the published peer-reviewed medical literature for papers reporting an association between joint hypermobility or Ehlers-Danlos syndrome and orthostatic intolerance. RESULTS: We identified 10 relevant papers. Although methodological variability between studies introduces some limitations, the published literature consistently identifies a significantly higher prevalence of orthostatic intolerance symptoms in patients with joint hypermobility or Ehlers-Danlos syndrome than in healthy controls, and a significantly higher prevalence of cardiovascular and autonomic abnormalities both at rest and during orthostatic challenge. Postural tachycardia syndrome is the most commonly recognized circulatory disorder. The severity of orthostatic symptoms in those with EDS correlates with impairments in quality of life. CONCLUSION: There is a strong association between several forms of cardiovascular dysfunction, most notably postural tachycardia syndrome, and joint hypermobility or Ehlers-Danlos syndrome. We propose that recognition of joint hypermobility and Ehlers-Danlos syndrome among those with orthostatic intolerance syndromes has the potential to improve clinical care and the validity of research findings.

Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome.

Chronic fatigue syndrome (CFS) is a complex, multisystem disorder that can be disabling. CFS symptoms can be provoked by increased physical or cognitive activity, and by orthostatic stress. In preliminary work, we noted that CFS symptoms also could be provoked by application of longitudinal neural and soft tissue strain to the limbs and spine of affected individuals. In this study we measured the responses to a straight leg raise neuromuscular strain maneuver in individuals with CFS and healthy controls. We randomly assigned 60 individuals with CFS and 20 healthy controls to either a 15 minute period of passive supine straight leg raise (true neuromuscular strain) or a sham straight leg raise. The primary outcome measure was the symptom intensity difference between the scores during and 24 hours after the study maneuver compared to baseline. Fatigue, body pain, lightheadedness, concentration difficulties, and headache scores were measured individually on a 0-10 scale, and summed to create a composite symptom score. Compared to individuals with CFS in the sham strain group, those with CFS in the true strain group reported significantly increased body pain (P = 0.04) and concentration difficulties (P = 0.02) as well as increased composite symptom scores (all P = 0.03) during the maneuver. After 24 hours, the symptom intensity differences were significantly greater for the CFS true strain group for the individual symptom of lightheadedness (P = 0.001) and for the composite symptom score (P = 0.005). During and 24 hours after the exposure to the true strain maneuver, those with CFS had significantly higher individual and composite symptom intensity changes compared to the healthy controls. We conclude that a longitudinal strain applied to the nerves and soft tissues of the lower limb is capable of increasing symptom intensity in individuals with CFS for up to 24 hours. These findings support our preliminary observations that increased mechanical sensitivity may be a contributor to the provocation of symptoms in this disorder.