Tag: Rowe

Chronic fatigue in Ehlers-Danlos syndrome-hypermobile type

Abstract:

Chronic fatigue is an important contributor to impaired health-related quality of life in Ehlers-Danlos syndrome. There is overlap in the symptoms and findings of EDS and chronic fatigue syndrome. A proportion of those with CFS likely have EDS that has not been identified.

The evaluation of chronic fatigue in EDS needs to include a careful clinical examination and laboratory testing to exclude common causes of fatigue including anemia, hypothyroidisim, and chronic infection, as well as dysfunction of major physiological or organ systems.

Other problems that commonly contribute to fatigue in EDS include sleep disorders, chronic pain, deconditioning, cardiovascular autonomic dysfunction, bowel and bladder dysfunction, psychological issues, and nutritional deficiencies.

While there is no specific pharmacological treatment for fatigue, many medications are effective for specific symptoms (such as headache, menstrual dysfunction, or myalgia) and for co-morbid conditions that result in fatigue, including orthostatic intolerance and insomnia.

Comprehensive treatment of fatigue needs to also evaluate for biomechanical problems that are common in EDS, and usually involves skilled physical therapy and attention to methods to prevent deconditioning.

In addition to managing specific symptoms, treatment of fatigue in EDS also needs to focus on maintaining function and providing social, physical, and nutritional support, as well as providing on-going medical evaluation of new problems and review of new evidence about proposed treatments.

© 2017 Wiley Periodicals, Inc.

 

Source: Hakim A, De Wandele I, O’Callaghan C, Pocinki A, Rowe P. Chronic fatigue in Ehlers-Danlos syndrome-hypermobile type. Am J Med Genet C Semin Med Genet. 2017 Feb 10. doi: 10.1002/ajmg.c.31542. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28186393

 

Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome

Abstract:

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.

 

Source: Rowe PC, Fontaine KR, Lauver M, Jasion SE, Marden CL, Moni M, Thompson CB, Violand RL. Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome. PLoS One. 2016 Jul 18;11(7):e0159386. doi: 10.1371/journal.pone.0159386. ECollection 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948885/ (Full article)

 

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

Abstract:

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.

©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

 

Source: Rowe PC, Marden CL, Jasion SE, Cranston EM, Flaherty MA, Kelly KJ. Cow’s milk protein intolerance in adolescents and young adults with chronic fatigue syndrome. Acta Paediatr. 2016 Sep;105(9):e412-8. doi: 10.1111/apa.13476. Epub 2016 Jun 3. https://www.ncbi.nlm.nih.gov/pubmed/27177188

 

Effects of low-dose clonidine on cardiovascular and autonomic variables in adolescents with chronic fatigue: a randomized controlled trial

Abstract:

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a common and disabling condition in adolescence with few treatment options. A central feature of CFS is orthostatic intolerance and abnormal autonomic cardiovascular control characterized by sympathetic predominance. We hypothesized that symptoms as well as the underlying pathophysiology might improve by treatment with the alpha2A-adrenoceptor agonist clonidine.

METHODS: A total of 176 adolescent CFS patients (12-18 years) were assessed for eligibility at a single referral center recruiting nation-wide. Patients were randomized 1:1 by a computer system and started treatment with clonidine capsules (25 μg or 50 μg twice daily, respectively, for body weight below/above 35 kg) or placebo capsules for 9 weeks. Double-blinding was provided. Data were collected from March 2010 until October 2012 as part of The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL). Effect of clonidine intervention was assessed by general linear models in intention-to-treat analyses, including baseline values as covariates in the model.

RESULTS: A total of 120 patients (clonidine group n = 60, placebo group n = 60) were enrolled and started treatment. There were 14 drop-outs (5 in the clonidine group, 9 in the placebo group) during the intervention period. At 8 weeks, the clonidine group had lower plasma norepinephrine (difference = 205 pmol/L, p = 0.05) and urine norepinephrine/creatinine ratio (difference = 3.9 nmol/mmol, p = 0.002). During supine rest, the clonidine group had higher heart rate variability in the low-frequency range (LF-HRV, absolute units) (ratio = 1.4, p = 0.007) as well as higher standard deviation of all RR-intervals (SDNN) (difference = 12.0 ms, p = 0.05); during 20° head-up tilt there were no statistical differences in any cardiovascular variable. Symptoms of orthostatic intolerance did not change during the intervention period.

CONCLUSIONS: Low-dose clonidine reduces catecholamine levels in adolescent CFS, but the effects on autonomic cardiovascular control are sparse. Clonidine does not improve symptoms of orthostatic intolerance.

TRIAL REGISTRATION: Clinical Trials ID: NCT01040429, date of registration 12/28/2009.

 

Source: Fagermoen E, Sulheim D, Winger A, Andersen AM, Gjerstad J, Godang K, Rowe PC, Saul JP, Skovlund E, Wyller VB. Effects of low-dose clonidine on cardiovascular and autonomic variables in adolescents with chronic fatigue: a randomized controlled trial. BMC Pediatr. 2015 Sep 10;15:117. doi: 10.1186/s12887-015-0428-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566847/ (Full article)

 

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

Abstract:

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.

Copyright © 2014 Elsevier Inc. All rights reserved.

 

Source: Rowe PC, Marden CL, Flaherty MA, Jasion SE, Cranston EM, Johns AS, Fan J, Fontaine KR, Violand RL. Impaired range of motion of limbs and spine in chronic fatigue syndrome. J Pediatr. 2014 Aug;165(2):360-6. doi: 10.1016/j.jpeds.2014.04.051. Epub 2014 Jun 11. https://www.ncbi.nlm.nih.gov/pubmed/24929332

 

Disease mechanisms and clonidine treatment in adolescent chronic fatigue syndrome: a combined cross-sectional and randomized clinical trial

Abstract:

IMPORTANCE: Chronic fatigue syndrome (CFS) is a disabling condition with unknown disease mechanisms and few treatment options.

OBJECTIVE: To explore the pathophysiology of CFS and assess clonidine hydrochloride pharmacotherapy in adolescents with CFS by using a hypothesis that patients with CFS have enhanced sympathetic activity and that sympatho-inhibition by clonidine would improve symptoms and function.

DESIGN, SETTING, AND PARTICIPANTS: Participants were enrolled from a single referral center recruiting nationwide in Norway. A referred sample of 176 adolescents with CFS was assessed for eligibility; 120 were included (34 males and 86 females; mean age, 15.4 years). A volunteer sample of 68 healthy adolescents serving as controls was included (22 males and 46 females; mean age, 15.1 years). The CSF patients and healthy controls were assessed cross-sectionally at baseline. Thereafter, patients with CFS were randomized 1:1 to treatment with low-dose clonidine or placebo for 9 weeks and monitored for 30 weeks; double-blinding was provided. Data were collected from March 2010 until October 2012 as part of the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial.

INTERVENTIONS: Clonidine hydrochloride capsules (25 µg or 50 µg twice daily for body weight <35 kg or >35 kg, respectively) vs placebo capsules for 9 weeks.

MAIN OUTCOMES AND MEASURES: Number of steps per day.

RESULTS: At baseline, patients with CFS had a lower number of steps per day (P < .001), digit span backward score (P = .002), and urinary cortisol to creatinine ratio (P = .001), and a higher fatigue score (P < .001), heart rate responsiveness (P = .02), plasma norepinephrine level (P < .001), and serum C-reactive protein concentration (P = .04) compared with healthy controls. There were no significant differences regarding blood microbiology evaluation. During intervention, the clonidine group had a lower number of steps per day (mean difference, -637 steps; P = .07), lower plasma norepinephrine level (mean difference, -42 pg/mL; P = .01), and lower serum C-reactive protein concentration (mean ratio, 0.69; P = .02) compared with the CFS placebo group.

CONCLUSIONS AND RELEVANCE: Adolescent CFS is associated with enhanced sympathetic nervous activity, low-grade systemic inflammation, attenuated hypothalamus-pituitary-adrenal axis function, cognitive impairment, and large activity reduction, but not with common microorganisms. Low-dose clonidine attenuates sympathetic outflow and systemic inflammation in CFS but has a concomitant negative effect on physical activity; thus, sympathetic and inflammatory enhancement may be compensatory mechanisms. Low-dose clonidine is not clinically useful in CFS.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01040429.

 

Source: Sulheim D, Fagermoen E, Winger A, Andersen AM, Godang K, Müller F, Rowe PC, Saul JP, Skovlund E, Øie MG, Wyller VB. Disease mechanisms and clonidine treatment in adolescent chronic fatigue syndrome: a combined cross-sectional and randomized clinical trial. JAMA Pediatr. 2014 Apr;168(4):351-60. doi: 10.1001/jamapediatrics.2013.4647. https://www.ncbi.nlm.nih.gov/pubmed/24493300

 

Neuromuscular strain as a contributor to cognitive and other symptoms in chronic fatigue syndrome: hypothesis and conceptual model

Abstract:

Individuals with chronic fatigue syndrome (CFS) have heightened sensitivity and increased symptoms following various physiologic challenges, such as orthostatic stress, physical exercise, and cognitive challenges. Similar heightened sensitivity to the same stressors in fibromyalgia (FM) has led investigators to propose that these findings reflect a state of central sensitivity.

A large body of evidence supports the concept of central sensitivity in FM. A more modest literature provides partial support for this model in CFS, particularly with regard to pain. Nonetheless, fatigue and cognitive dysfunction have not been explained by the central sensitivity data thus far.

Peripheral factors have attracted attention recently as contributors to central sensitivity. Work by Brieg, Sunderland, and others has emphasized the ability of the nervous system to undergo accommodative changes in length in response to the range of limb and trunk movements carried out during daily activity. If that ability to elongate is impaired-due to movement restrictions in tissues adjacent to nerves, or due to swelling or adhesions within the nerve itself-the result is an increase in mechanical tension within the nerve. This adverse neural tension, also termed neurodynamic dysfunction, is thought to contribute to pain and other symptoms through a variety of mechanisms. These include mechanical sensitization and altered nociceptive signaling, altered proprioception, adverse patterns of muscle recruitment and force of muscle contraction, reduced intra-neural blood flow, and release of inflammatory neuropeptides. Because it is not possible to differentiate completely between adverse neural tension and strain in muscles, fascia, and other soft tissues, we use the more general term “neuromuscular strain.”

In our clinical work, we have found that neuromuscular restrictions are common in CFS, and that many symptoms of CFS can be reproduced by selectively adding neuromuscular strain during the examination. In this paper we submit that neuromuscular strain is a previously unappreciated peripheral source of sensitizing input to the nervous system, and that it contributes to the pathogenesis of CFS symptoms, including cognitive dysfunction.

 

Source: Rowe PC, Fontaine KR, Violand RL. Neuromuscular strain as a contributor to cognitive and other symptoms in chronic fatigue syndrome: hypothesis and conceptual model. Front Physiol. 2013 May 16;4:115. doi: 10.3389/fphys.2013.00115. eCollection 2013.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655286/ (Full article)

 

Cervical spine stenosis as a cause of severe ME/CFS and orthostatic intolerance symptoms

Background: Comparatively little has been published on the clinical features and management of severe forms of ME/CFS.

Objectives: To describe the presenting symptoms and neurological examination findings in three young adult women whose disabling ME/CFS symptoms and orthostatic intolerance improved after the recognition and surgical management of cervical spine stenosis (CSS).

Methods: This retrospective case series includes three consecutive individuals who (1) met the Fukuda and criteria for CFS, (2) had evidence of refractory orthostatic intolerance, (3) were unable to work or attend school, and (4) were minimally responsive to medical and psychiatric management. To investigate pathological reflex findings, all underwent MRI evaluations. CSS was considered present if the AP cervical spinal canal diameter (SCD) was less than 10 mm at any level. Overall function was assessed before and after cervical disc replacement surgery using (1) a clinician-assigned Karnofsky score (range 0 to 100) and (2) the SF-36 physical function (PF) subscale score (range 10-30). Higher scores indicate better function on both measures.

Results: Age at onset of symptoms was 12, 29, and 29 years. The onset of ME/CFS was acute in all three. Neurological exam findings included > 3+ (brisk) deep tendon reflexes (DTR) in 2/3, positive Hoffman sign in 2/3, tremor in 2/3, and absent gag reflex in 1/3. Diagnosis was delayed for 6-9 years after the onset of symptoms. Brain MRIs were normal. The youngest patient had congenital CSS with a single level disc protrusion at C5-6 that caused further ventral cord compression and a SCD of 7 mm. Her mother also has cervical stenosis. A second
patient had two disc protrusions at C5-6 and C6-7 with SCD of 7 and 9 mm, and myelomalacia (this patient has a sibling with Chiari I malformation). The third had acquired CSS due to a single level disc bulge at C5-6 (SCD = 8.5 mm).

Improvements were evident within 2 months of single-level cervical disc replacement surgery (one patient also had fusion at an adjacent level). After 16-40 months of follow-up, all reported improved fatigue, cognitive dysfunction, PEM, lightheadedness, and anxiety. The pre- to post-op SF-36 PF scores improved from 13 to 30, 18 to 30, and 16 to 26, respectively, and the Karnofsky scores improved from 40 to 90, 40 to 90, and 50 to 100, respectively. Standing tests conducted at variable intervals from pre- to post-op showed a reduction in the maximal heart rate (HR) change during 5 minutes of standing from 64 to 22 bpm, 42 to 29 bpm, and 34 to 27 bpm, respectively.

Conclusion: This case series draws attention to the potential for CSS to contribute to ME/CFS and orthostatic symptoms, extending work by Heffez in fibromyalgia (Eur Spine J 2004;13:516). Further work is needed to define indications for surgery. However, the improvements in HR and function following surgery emphasize the importance of detecting and treating CSS, especially in the subset of those with ME/CFS whose severe symptoms are refractory to other interventions.

Peter C. Rowe, M.D.
Professor of Pediatrics
Johns Hopkins University School of Medicine/200 N. Wolfe Street/Room 2077
Baltimore, MD 21287
prowe@jhmi.edu

Dr. Rowe is supported by the Sunshine Natural Wellbeing Foundation Professorship in Chronic Fatigue and Related Disorders. No author has a conflict of interest.

 

Source: Peter C. Rowe, M.D*, Colleen L. Marden, Scott Heinlein, PT, Charles Edwards II, M.D. Cervical spine stenosis as a cause of severe ME/CFS and orthostatic intolerance symptoms. Poster presentation, IACFS/ME 2016 conference.

 

Severe versus Moderate criteria for the new pediatric case definition for ME/CFS

Abstract:

The new diagnostic criteria for pediatric ME/CFS are structurally based on the Canadian Clinical Adult case definition, and have more required specific symptoms than the (Fukuda et al. Ann Intern Med 121:953-959, 1994) adult case definition.

Physicians specializing in pediatric ME/CFS referred thirty-three pediatric patients with ME/CFS and 21 youth without the illness. Those who met ME/CFS criteria were separated into Severe and Moderate categories. Significant differences were found for symptoms within each of the six major categories: fatigue, post-exertional malaise, sleep, pain, neurocognitive difficulties, and autonomic/neuroendocrine/immune manifestations.

In general, the results showed participants who met the Severe ME/CFS criteria reported the highest scores, the Moderate ME/CFS group show scores that were a little lower, and the control group evidenced the lowest scores. Findings indicate that the Pediatric Case Definition for ME/CFS can distinguish between those with this illness and controls, and between those with Severe versus Moderate manifestations of the illness.

 

Source: Jason L, Porter N, Shelleby E, Till L, Bell DS, Lapp CW, Rowe K, De Meirleir K. Severe versus Moderate criteria for the new pediatric case definition for ME/CFS. Child Psychiatry Hum Dev. 2009 Dec;40(4):609-20. doi: 10.1007/s10578-009-0147-8. Epub 2009 Jun 10.https://www.ncbi.nlm.nih.gov/pubmed/19513826

 

Successful use of a primary care practice-specialty collaboration in the care of an adolescent with chronic fatigue syndrome

Abstract:

We report on the successful collaborative care of an adolescent with chronic fatigue syndrome between a primary care pediatrician and an academic chronic fatigue syndrome specialist located in different cities. Regular telephone and e-mail communication and clearly defined patient-care roles allowed for timely management of symptoms and marked clinical improvement. We discuss ways to improve the collaboration of primary care and subspecialty physicians for patients with chronic fatigue syndrome and children with special health care needs.

 

Source: Kuo DZ, Cheng TL, Rowe PC. Successful use of a primary care practice-specialty collaboration in the care of an adolescent with chronic fatigue syndrome. Pediatrics. 2007 Dec;120(6):e1536-9. https://www.ncbi.nlm.nih.gov/pubmed/18055669