Category: Conference

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.

 

Assessment of Cellular Bioenergetics in Chronic Fatigue Syndrome

Introduction: Abnormalities in bioenergetic function have been cited as one possible cause for chronic fatigue syndrome (CFS). One hypothesis to explain this suggests that CFS may be caused, at least in part, by an acquired mitochondrial dysfunction.

Extracellular flux analysers make real-time, in vitro assessment of cellular energy pathways possible. Using this technology, mitochondrial function can be measured in a variety of cell types in real-time thus increasing our understanding of the role of metabolism in CFS.

Objectives: This project aims to utilise extracellular flux detection technology in order to investigate the cellular bioenergetics of different cell types obtained from CFS patients and healthy controls.

Methods: Mitochondrial stress tests were conducted using skeletal muscle cells and peripheral blood mononuclear cells (PBMCs) derived from CFS patients and controls. During this test mitochondrial complexes are inhibited in turn to modulate respiration so mitochondrial function can be evaluated. The oxygen consumption rate of cells is measured which allows keys parameters of mitochondrial function to be measured and calculated in a single experiment, providing an overall assessment of mitochondrial function. Parameters measured are: basal respiration, maximal respiration and non-mitochondrial respiration. Proton leak, ATP-production and spare respiratory capacity are subsequently able to be calculated using the three measured parameters. CFS patients whose samples were used in these studies were diagnosed using the Fukuda definition.

Results: Results using skeletal muscle cells obtained from CFS patients (n=3) and controls (n=5), indicate that there is no difference in the energy profiles of the skeletal muscle cells of CFS patients in any of the parameters investigated.

Mitochondrial stress test results using PBMCs show CFS PBMCs (n=7) to be significantly lower than control cells (n=10) in all parameters investigated (p≤0.016). Importantly, these results suggest that CFS PBMCs perform closer to their maximum under normal conditions. This means that when CFS PBMCs come under stress they are less able to increase their respiration rate to compensate for the increase in stress.

Conclusions: These findings provide an interesting starting point for investigations into cellular bioenergetics in CFS.

Cara Jasmine Tomas; First year medical science PhD student; Institute of Cellular Medicine, Level 1, William Leech Building, Medical School, Newcastle University, Newcastle Upon-Tyne, NE2 4HH, England; c.j.tomas@ncl.ac.uk
This work was funded by the Medical Research Council and Newcastle University.

 

Source: Cara Tomas, Julia Newton, Audrey Brown, Gina Rutherford, Philip Manning
Newcastle University, UK. Assessment of Cellular Bioenergetics in Chronic Fatigue Syndrome. Poster presentation, IACFS/ME 2016 conference.

Immunologic aspects of chronic fatigue syndrome. Report on a Research Symposium convened by The CFIDS Association of America and co-sponsored by the US Centers for Disease Control and Prevention and the National Institutes of Health

Abstract:

Chronic fatigue syndrome (CFS) is a serious health concern affecting over 800,000 Americans of all ages, races, socioeconomic groups and genders. The etiology and pathophysiology of CFS are unknown, yet studies have suggested an involvement of the immune system.

A symposium was organized in October 2001 to explore the possibility of an association between immune dysfunction and CFS, with special emphasis on the interactions between immune dysfunction and other abnormalities noted in the neuroendocrine and autonomic nervous systems of individuals with CFS. This paper represents the consensus of the panel of experts who participated in this meeting.

Data suggest that persons with CFS manifest changes in immune responses that fall outside normative ranges, but current research does not provide definitive evidence on whether these immune abnormalities are a cause or result of the illness. It has become clear that CFS cannot be understood based on single measurements of immune, endocrine, cardiovascular, or autonomic nervous system dysfunction. This panel encourages a new emphasis on multidisciplinary research into CFS.

 

Source: Gerrity TR, Papanicolaou DA, Amsterdam JD, Bingham S, Grossman A, Hedrick T, Herberman RB, Krueger G, Levine S, Mohagheghpour N, Moore RC,Oleske J, Snell CR; CFIDS Association of America. Immunologic aspects of chronic fatigue syndrome. Report on a Research Symposium convened by The CFIDS Association of America and co-sponsored by the US Centers for Disease Control and Prevention and the National Institutes of Health. Neuroimmunomodulation. 2004;11(6):351-7. http://www.ncbi.nlm.nih.gov/pubmed/15467349

 

Neuroendocrine aspects of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a serious health concern affecting over 800000 Americans of all ages, races, socioeconomic groups and genders. The etiology and pathophysiology of CFS are unknown, yet studies have suggested an involvement of the neuroendocrine system. A symposium was organized in March 2001 to explore the possibility of an association between neuroendocrine dysfunction and CFS, with special emphasis on the interactions between neuroendocrine dysfunction and other abnormalities noted in the immune and autonomic nervous systems of individuals with CFS. This paper represents the consensus of the panel of experts who participated in this meeting.

Copyright 2004 S. Karger AG, Basel

 

Source: Papanicolaou DA1, Amsterdam JD, Levine S, McCann SM, Moore RC, Newbrand CH, Allen G, Nisenbaum R, Pfaff DW, Tsokos GC, Vgontzas AN, Kales A. Neuroendocrine aspects of chronic fatigue syndrome. Neuroimmunomodulation. 2004;11(2):65-74. http://www.ncbi.nlm.nih.gov/pubmed/14758052

 

Chronic fatigue syndrome: what role does the autonomic nervous system play in the pathophysiology of this complex illness?

Abstract:

Chronic fatigue syndrome (CFS) is a serious health concern affecting over 800000 Americans of all ages, races and socioeconomic groups and both genders. The etiology and pathophysiology of CFS are unknown, yet studies have suggested an involvement of the autonomic nervous system (ANS). A symposium was organized in December 2000 to explore the possibility of an association between ANS dysfunction and CFS, with special emphasis on the interactions between ANS dysfunction and other abnormalities noted in the immune and endocrine systems of individuals with CFS. This paper represents the consensus of the panel of experts who participated in this meeting.

Copyright 2002 S. Karger AG, Basel

 

Source: Gerrity TR, Bates J, Bell DS, Chrousos G, Furst G, Hedrick T, Hurwitz B, Kula RW, Levine SM, Moore RC, Schondorf R. Chronic fatigue syndrome: what role does the autonomic nervous system play in the pathophysiology of this complex illness? Neuroimmunomodulation. 2002-2003;10(3):134-41. http://www.ncbi.nlm.nih.gov/pubmed/12481153

 

The role of environmental factors in medically unexplained symptoms and related syndromes: conference summary and recommendations

Abstract:

This monograph of peer-reviewed articles is based on presentations at the conference “Environmental Factors in Medically Unexplained Physical Symptoms and Related Syndromes” held 10-12 January 2001 in Piscataway, New Jersey, USA. The purpose of the conference was to determine research priorities for elucidating the role of environmental factors in medically unexplained symptoms and symptom syndromes. These include conditions such as chronic fatigue syndrome, multiple chemical sensitivities, sick building syndrome, Gulf War illness, and the like. Approximately 1 1/2 days were devoted to plenary talks and 1 day was devoted to break-out sessions to discuss epidemiologic, psychosocial, and experimental research. Recommendations were made for a series of epidemiologic, psychosocial, and experimental research approaches, with acknowledgment that nosology issues are clearly fundamental to advancing understanding of these conditions.

 

Source: Kipen HM, Fiedler N. The role of environmental factors in medically unexplained symptoms and related syndromes: conference summary and recommendations. Environ Health Perspect. 2002 Aug;110 Suppl 4:591-5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241210/ (Full article)

 

Chronic fatigue syndrome: point and counterpoint

Abstract:

Two clinical investigators with divergent views on chronic fatigue syndrome (CFS) were invited to debate their positions at the 1993 annual meeting of The Infectious Disease Society of America. Major points of the discourse focused on the value of the US Centers for Disease Control and Prevention case definition of CFS, the potential roles of infectious and allergic problems in the syndrome, the confounding problem of concurrent psychiatric problems, and the utility of diagnostic tests.

 

Source: Straus SE, Komaroff AL, Wedner HJ. Chronic fatigue syndrome: point and counterpoint. J Infect Dis. 1994 Jul;170(1):1-6. http://www.ncbi.nlm.nih.gov/pubmed/8014482

 

The neuropsychiatry of chronic fatigue syndrome

Abstract:

This paper explores the relationship between chronic fatigue syndrome (CFS) and psychiatric disorder, with special reference to neuropsychiatry, Topics reviewed include (1) epidemiological evidence of central disorder in CFS; (2) evidence from longitudinal studies of an interaction between vulnerability to CFS and psychiatric disorder; and (3) evidence from neuroimaging, neuropsychology, neurophysiology and neuroendocrinology of disordered CNS function in CFS. The most impressive evidence of CNS disturbance comes from neuroendocrinological studies, which suggest a role of hypothalamic disorder as a final common pathway for CFS. It is concluded that the equal and opposite tendencies of psychiatry to be ‘brainless’ and neurology to be ‘mindless’ have led to needless controversy over the nature of CFS. Now that the contributions of psychiatric disorder to CFS, and of neurobiological dysfunction to psychiatric disorder, are both established, it will be possible to make real advances in understanding the nature of CFS.

 

Source: Wessely S. The neuropsychiatry of chronic fatigue syndrome. Ciba Found Symp. 1993;173:212-29; discussion 229-37. http://www.ncbi.nlm.nih.gov/pubmed/8491099

 

Muscle histopathology and physiology in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterized by fatigue at rest which is made worse by exercise. Previous biopsy studies on small numbers of CFS patients have shown a range of morphological changes to which have been attributed fatigue and myalgia.

We have now studied 108 patients with CFS or muscle pain and 22 normal volunteers by light and electron microscopy. There was no consistent correlation between symptoms and changes in fibre type prevalence, fibre size, degenerative or regenerative features, glycogen depletion, or mitochondrial abnormalities. Physiological contractile properties of quadriceps (maximal isometric force generation, frequency: force characteristics and relaxation rate) were also examined before and for up to 48 hours after a symptom-limited incremental cycle ergometer exercise test in 12 CFS patients and 12 normal volunteers.

Voluntary and stimulated force characteristics were normal at rest and during recovery. Exercise duration was similar in the two groups although CFS patients had higher perceived exertion scores in relation to heart rate during exercise, indicating a reduced effort sensation threshold. On physiological and pathological grounds it is clear that CFS is not a myopathy. Psychological/psychiatric factors appear to be of greater importance in this condition.

 

Source: Edwards RH1, Gibson H, Clague JE, Helliwell T. Muscle histopathology and physiology in chronic fatigue syndrome. Ciba Found Symp. 1993;173:102-17; discussion 117-31. http://www.ncbi.nlm.nih.gov/pubmed/8491096

 

Investigation of retroviral involvement in chronic fatigue syndrome

Abstract:

Within the last few years significant efforts have been made to identify objective reliable diagnostic markers from individuals with chronic fatigue syndrome (CFS).

We report the absence of a previously described retroviral marker (HTLV-II gag) in a blinded study of CFS cases. Even with excellent reproducible sensitivities, this marker failed in repeated attempts to distinguish cases from controls. In addition, four other retroviruses (simian T cell leukaemia virus, human spumavirus, bovine leukaemia virus and simian retrovirus) were examined for their presence in these CFS cases and found to be absent.

Our findings suggest that these agents, at least as markers, are non-distinguishing for CFS and that other factors may be confounding the resolution of an aetiology to this syndrome.

 

Source: Folks TM, Heneine W, Khan A, Woods T, Chapman L, Schonberger L. Investigation of retroviral involvement in chronic fatigue syndrome. Ciba Found Symp. 1993;173:160-6; discussion 166-75. http://www.ncbi.nlm.nih.gov/pubmed/8387909