dysautonomia – Page 10 – American ME and CFS Society

Midodrine treatment for chronic fatigue syndrome

Abstract:

The long term results of midodrine treatment in a patient having debilitating chronic fatigue syndrome (CFS) are reported. Midodrine treatment, directed at the autonomic nervous system, resulted in correction of the dysautonomia followed by improvement of fatigue. This finding is consistent with the hypothesis that dysautonomia plays a major part in the pathophysiology of CFS and that therapies directed at the autonomic nervous system may be effective in the treatment of CFS.

Source: Naschitz J, Dreyfuss D, Yeshurun D, Rosner I. Midodrine treatment for chronic fatigue syndrome. Postgrad Med J. 2004 Apr;80(942):230-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1742969/pdf/v080p00230.pdf (Full article)

Autonomic function and serum erythropoietin levels in chronic fatigue syndrome

Abstract:

OBJECTIVE: Given previous findings, we wished to investigate whether there was evidence of autonomic dysfunction in patients with chronic fatigue syndrome, and whether this could be related to reduced erythropoietin levels and altered red blood cell indices.

METHODS: We assessed autonomic function and analysed blood parameters (including erythropoietin) in 22 patients with chronic fatigue syndrome who were medication-free and without comorbid depression or anxiety. Results were compared to 23 iron-deficiency anaemia patients and 18 healthy individuals.

RESULTS: Autonomic testing in patients with chronic fatigue syndrome yielded a significantly greater increase in heart rate together with a more pronounced systolic blood pressure fall on standing compared to healthy individuals. Heart rate beat-to-beat variation on deep breathing and responses to the Valsalva manoeuvre were normal. Two of 22 patients with chronic fatigue had mild normochromic normocytic anaemia with normal ferritin, vitamin B12 and folate levels. Serum erythropoietin levels were within reference range.

CONCLUSION: Some autonomic dysfunction is present in chronic fatigue syndrome (CFS) patients; the explanation remains uncertain, but could relate to cardiovascular deconditioning. There were no major haematological, biochemical or immunological abnormalities in these patients.

Source: Winkler AS, Blair D, Marsden JT, Peters TJ, Wessely S, Cleare AJ. Autonomic function and serum erythropoietin levels in chronic fatigue syndrome. J Psychosom Res. 2004 Feb;56(2):179-83. http://www.ncbi.nlm.nih.gov/pubmed/15016575

Dysautonomia in chronic fatigue syndrome: facts, hypotheses, implications

Abstract:

The diagnosis of chronic fatigue syndrome (CFS) is based on patient history and treatment on cognitive behavior therapy and graded exercise. There is increasing evidence that dysautonomia occurs in CFS manifest primarily as disordered regulation of cardiovascular responses to stress. We impart our experience relating to diagnosis, monitoring, and treatment of CFS based on identification and management of dysautonomia.

Recently proposed methods for assessment of the cardiovascular reactivity, the ‘hemodynamic instability score’ (HIS) and the ‘Fractal and Recurrence Analysis-based Score’ (FRAS), served for this purpose. On HUTT, a particular dysautonomia is revealed in CFS patients that differ from dysautonomia in several other disorders. This distinct abnormality in CFS can be identified by HIS >-0.98 (sensitivity 84.5% and specificity 85.1%) and FRAS > +0.22 (sensitivity 70% and specificity 88%). Therefore, the HIS and FRAS may be used, in the appropriate clinical context, to support the diagnosis of CFS, which until now, could only be subjectively inferred.

A pilot study suggested that midodrine treatment, directed at the autonomic nervous system in CFS, results first in correction of dysautonomia followed by improvement of fatigue. This finding implies that dysautonomia is pivotal in the pathophysiology CFS, at least in a large part of the patients, and that manipulating the autonomic nervous system may be effective in the treatment of CFS.

Source: Naschitz JE, Yeshurun D, Rosner I. Dysautonomia in chronic fatigue syndrome: facts, hypotheses, implications. Med Hypotheses. 2004;62(2):203-6. http://www.ncbi.nlm.nih.gov/pubmed/14962627

The head-up tilt test in the diagnosis and management of chronic fatigue syndrome

Fatigue, as a symptom, refers to a sense of lethargy or loss of energy. Fatigue is common in infections, endocrine disorders, heart failure, chronic diseases of the lungs, liver or kidneys, malignancies, anemia, nutritional deficits, inflammatory arthritis, Parkinson’s disease, depression, anxiety states, effect of certain medications, or drug withdrawal [1]. Population-based studies show that fatigue is one of the most common somatic symptoms, with as much as 20± 30% of the population complaining of chronic fatigue [2]. Only a small fraction of these satisfy the clinical definition criteria for chronic fatigue syndrome [1].

You can read the rest of this article here: https://www.ima.org.il/FilesUpload/IMAJ/0/54/27402.pdf

Source: Naschitz JE, Sabo E, Dreyfuss D, Yeshurun D, Rosner I. The head-up tilt test in the diagnosis and management of chronic fatigue syndrome. Isr Med Assoc J. 2003 Nov;5(11):807-11. https://www.ima.org.il/FilesUpload/IMAJ/0/54/27402.pdf (Full article)

Efficacy of a half dose of oral pyridostigmine in the treatment of chronic fatigue syndrome: three case reports

Abstract:

Chronic fatigue syndrome (CFS) is characterized by persistent mental and physical fatigue for at least 6 months. Its pathophysiology is unknown and there is no proven effective treatment. We describe three cases who fulfill the criteria of CFS, in whom a defect of neuromuscular transmission and dysautonomia are present and who respond to acetylcholine-esterase inhibition.

Case 1: 18-year-old female with a 3-year history of CFS. Response of compound-muscle-action potential, recorded using surface recording electrode, over left abductor pollicis brevis muscle, to repetitive nerve stimulation (RNS) at a rate of 10 Hz showed a 42% incremental response. Composite autonomic scoring system (CASS) showed mild cholinergic impairment (cardiovagal score: 1; sudomotor score: 2). Serological tests for Epstein-Barr virus (EBV) revealed positive antiviral capsid antigens (anti-VCA) immunoglobulins G (IgG). Oral pyridostigmine therapy (30 mg) resulted in marked improvement in symptoms.

Case 2: 28-year-old female with 10-year history of CFS. RNS, using identical protocol, showed a 60% incremental response over the same muscle. CASS showed mild cholinergic impairment (cardiovagal score: 1; sudomotor score: 2) and this patient was also positive for EBV. This patient responded dramatically to 10-mg pyridostigmine.

Case 3: 29-year-old female with a history of CFS for longer than 15 years. Repetitive stimulation, using identical paradigm to left abductor pollicis brevis muscle, showed a 42% incremental response. CASS showed mildly cholinergic impairment (cardiovagal score: 2; sudomotor score: 1). EBV antibody titers were positive. Patient responded to 30-mg pyridostigmine with an improvement in her fatigue.

These three cases generate the hypothesis that the fatigue in some patients with clinical CFS might be due to a combination of mild neuromuscular transmission defect combined with cholinergic dysautonomia. Support for this thesis derives from the improvement with cholinesterase inhibition.

Source: Kawamura Y, Kihara M, Nishimoto K, Taki M. Efficacy of a half dose of oral pyridostigmine in the treatment of chronic fatigue syndrome: three case reports. Pathophysiology. 2003 May;9(3):189-194. http://www.ncbi.nlm.nih.gov/pubmed/14567934

The head-up tilt test for diagnosing chronic fatigue syndrome

Comment on: The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome. [QJM. 2003]

Sir,

The recent paper by Naschitz et al. on the use of the head‐up tilt test with haemodynamic instability score (HIS) in the diagnosis of chronic fatigue syndrome (CFS) provides additional insight about the role of dysautonomia in the pathogenesis of CFS. We would like to raise some points regarding the patient group studied.

The enrolment of clinically‐diagnosed CFS patients and the awareness of diagnosis by technicians prior to performing the tilt test, could result in selection bias. Additionally, generalizing the result of the study, whose population was rich in patients with CFS (40/349, or 11%) to the general population (prevalence of CFS 0.07–0.2%) could be misleading. Using their results of a sensitivity of 90.3% and specificity of 84.5% for a cutoff of HIS >−0.98, a positive head‐up tilt test in a patient presenting with fatigue in the general population would have a positive predictive value of only 0.37–1.15. This result, taken with the fact that around one‐fifth of the patients developed a presyncopal or syncopal episode, would make the test less appealing to patients. However, in a patient presenting with fatigue where clinical diagnosis remained unclear despite lengthy evaluation, the head‐up tilt test could be useful for narrowing down the range of diagnoses.

You can read the rest of this comment here: http://qjmed.oxfordjournals.org/content/96/5/379.2.long

Source: Ghosh AK, Ghosh K. The head-up tilt test for diagnosing chronic fatigue syndrome. QJM. 2003 May;96(5):379-80. http://qjmed.oxfordjournals.org/content/96/5/379.2.long (Full article)

The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome

Abstract:

BACKGROUND: Studying patients with chronic fatigue syndrome (CFS), we have developed a method that uses a head-up tilt test (HUTT) to estimate BP and HR instability during tilt, expressed as a ‘haemodynamic instability score’ (HIS).

AIM: To assess HIS sensitivity and specificity in the diagnosis of CFS.

DESIGN: Prospective controlled study.

METHODS: Patients with CFS (n=40), non-CFS chronic fatigue (n=73), fibromyalgia (n=41), neurally mediated syncope (n=58), generalized anxiety disorder (n=28), familial Mediterranean fever (n=50), arterial hypertension (n=28), and healthy subjects (n=59) were evaluated with a standardized head-up tilt test (HUTT). The HIS was calculated from blood pressure (BP) and heart rate (HR) changes during the HUTT.

RESULTS: The tilt was prematurely terminated in 22% of CFS patients when postural symptoms occurred and the HIS could not be calculated. In the remainder, the median(IQR) HIS values were: CFS +2.14(4.67), non-CFS fatigue -3.98(5.35), fibromyalgia -2.81(2.62), syncope -3.7(4.36), generalized anxiety disorder -0.21(6.05), healthy controls -2.66(3.14), FMF -5.09(6.41), hypertensives -5.35(2.74) (p<0.0001 vs. CFS in all groups, except for anxiety disorder, p=NS). The sensitivity for CFS at HIS >-0.98 cut-off was 90.3% and the overall specificity was 84.5%.

DISCUSSION: There is a particular dysautonomia in CFS that differs from dysautonomia in other disorders, characterized by HIS >-0.98. The HIS can reinforce the clinician’s diagnosis by providing objective criteria for the assessment of CFS, which until now, could only be subjectively inferred.

Comment in:

The head-up tilt test for diagnosing chronic fatigue syndrome. [QJM. 2003]

Assessing chronic fatigue. [QJM. 2003]

Source: Naschitz JE, Rosner I, Rozenbaum M, Naschitz S, Musafia-Priselac R, Shaviv N, Fields M, Isseroff H, Zuckerman E, Yeshurun D, Sabo E. The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome. QJM. 2003 Feb;96(2):133-42. http://qjmed.oxfordjournals.org/content/96/2/133.long (Full article)

Assessment of cardiovascular reactivity by fractal and recurrence quantification analysis of heart rate and pulse transit time

Abstract:

Methods used for the assessment of cardiovascular reactivity are flawed by nonlinear dynamics of the cardiovascular responses to stimuli. In an attempt to address this issue, we utilized a short postural challenge, recorded beat-to-beat heart rate (HR) and pulse transit time (PTT), assessed the data by fractal and recurrence quantification analysis, and processed the obtained variables by multivariate statistics. A 10-min supine phase of the head-up tilt test was followed by recording 600 cardiac cycles on tilt, that is, 5-10 min.

Three groups of patients were studied, each including 20 subjects matched for age and gender–healthy subjects, patients with essential hypertension (HT), and patients with chronic fatigue syndrome (CFS). The latter group was studied on account of the well-known dysautonomia of CFS patients, which served as contrast against the cardiovascular reactivity of the healthy population. A total of 52 variables of the HR and PTT were determined in each subject.

The multivariate model identified the best predictors for the assessment of reactivity of healthy subjects vs CFS. Based on these predictors, the “Fractal & Recurrence Analysis-based Score” (FRAS) was calculated: FRAS=76.2+0.04*HR-supine-DET -12.9*HR-tilt-R/L -0.31*HR-tilt-s.d. -19.27*PTT-tilt-R/L -9.42*PTT-tilt-WAVE. The median values and IQR of FRAS in the groups were: healthy=-1.85 (IQR 1.89), hypertensives=+0.52 (IQR 5.78), and CFS=-24.2 (5.34) (HT vs healthy subjects: P=0.0036; HT vs CFS: P<0.0001). Since the FRAS differed significantly between the three groups, it appears likely that the FRAS may recognize phenotypes of cardiovascular reactivity.

Source: Naschitz JE, Rosner I, Shaviv N, Khorshidi I, Sundick S, Isseroff H, Fields M, Priselac RM, Yeshurun D, Sabo E.Erratum in: J Hum Hypertens. 2003 Aug;17(8):585. Itzhak, R [corrected to Rosner, I]. Assessment of cardiovascular reactivity by fractal and recurrence quantification analysis of heart rate and pulse transit time. J Hum Hypertens. 2003 Feb;17(2):111-8. http://www.ncbi.nlm.nih.gov/pubmed/12574789

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.

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

Dysautonomias: clinical disorders of the autonomic nervous system

Abstract:

The term dysautonomia refers to a change in autonomic nervous system function that adversely affects health. The changes range from transient, occasional episodes of neurally mediated hypotension to progressive neurodegenerative diseases; from disorders in which altered autonomic function plays a primary pathophysiologic role to disorders in which it worsens an independent pathologic state; and from mechanistically straightforward to mysterious and controversial entities.

In chronic autonomic failure (pure autonomic failure, multiple system atrophy, or autonomic failure in Parkinson disease), orthostatic hypotension reflects sympathetic neurocirculatory failure from sympathetic denervation or deranged reflexive regulation of sympathetic outflows. Chronic orthostatic intolerance associated with postural tachycardia can arise from cardiac sympathetic activation after “patchy” autonomic impairment or blood volume depletion or, as highlighted in this discussion, from a primary abnormality that augments delivery of the sympathetic neurotransmitter norepinephrine to its receptors in the heart. Increased sympathetic nerve traffic to the heart and kidneys seems to occur as essential hypertension develops.

Acute panic can evoke coronary spasm that is associated with sympathoneural and adrenomedullary excitation. In congestive heart failure, compensatory cardiac sympathetic activation may chronically worsen myocardial function, which rationalizes treatment with beta-adrenoceptor blockers. A high frequency of positive results on tilt-table testing has confirmed an association between the chronic fatigue syndrome and orthostatic intolerance; however, treatment with the salt-retaining steroid fludrocortisone, which is usually beneficial in primary chronic autonomic failure, does not seem to be beneficial in the chronic fatigue syndrome. Dysautonomias are an important subject in clinical neurocardiology.

Source: Goldstein DS, Robertson D, Esler M, Straus SE, Eisenhofer G. Dysautonomias: clinical disorders of the autonomic nervous system. Ann Intern Med. 2002 Nov 5;137(9):753-63. http://www.ncbi.nlm.nih.gov/pubmed/12416949