Chronic Fatigue Syndrome Defined
The chronic fatigue syndrome (CFS) has been defined as a
distinct clinical entity characterized by chronic, often
relapsing, but always debilitating fatigue lasting for at least 6
months and causing impaired overall physical and mental
functioning. Recent CDC criteria (1994) have been broadly
formulated in order to standardize research in the field
resulting in an operating framework which includes cognitive
difficulties, pharyngitis, tender lymphadenopathy, muscle pain,
joint pain, headache, sleep disturbance or poor sleep, and post-exercise
malaise as central features of the illness. Since a precise
etiology for the syndrome remains elusive, the diagnosis is
largely made by exclusion once specific medical and psychiatric
disorders are ruled out. A central imperative, is to determine to
as great an extent as possible, whether there are any single or
relatively small set of pathophysiologic entities causing the
syndrome.
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Varied Pathophysiology Proposed for CFS
Investigations into the pathophysiology of CFS have remained
inconclusive although several possibilities exist. For example,
it might be expected that CFS patients could demonstrate striated
muscle deficiencies. However, skeletal muscle energetics,
structure and histopathology, physiology, and glycolytic activity
have been normal and electromyographic results have been
inconclusive in these patients. In vivo analyses of muscle
energetics are similarly suggestive but not definitive. Cardiac
studies have not consistently demonstrated defects in day-to-day
cardiac fitness among CFS patients compared to other
deconditioned people. Infectious and immune pathology have often
been suspected but not conclusively demonstrated as major
etiologic factors although studies hint at impaired inflammatory
cytokines and cellular immunity.
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Altered Regulatory Systems in CFS
Studies of the integrative and regulatory systems
have been provocative; there seems compelling information
concerning abnormalities in the cardiovascular regulatory areas
of the brainstem and in other vasoregulatory CNS which areas may
be associated with impaired vagal tone in response to
synchronized breathing malfunction of central and peripheral
nervous system, an inability to completely activate skeletal
muscle , and abbreviated exercise capacity due to inappropriately
low heart rate and early fatigue during treadmill testing.
Associated neuroendocrine dysfunction, impaired hypothalamic-pituitary-adrenal
interactions, and associated neurohumoral findings which can
produce impairment in cardiovascular regulation of the blood
pressure and cardiac output have been described. There is thus
evidence for a deficit in neuroendocrine regulatory mechanisms
which may limit organ and tissue function directly, or indirectly
through decreased blood pressure and impaired tissue level
perfusion. The peripheral circulatory beds and central nervous
system are particularly vulnerable to cardiovascular inadequacy.
Whether dysfunctional cardiovascular homeostasis is a primary
abnormality in CFS or whether it is a secondary effect may not be
critical in this regard: maladaptive changes in blood pressure
and blood flow could easily produce many of the signs and
symptoms associated with CFS such as light-headedness, impaired
cognition, inappropriate sweating and temperature instability.
The possibility that CFS findings result from low blood pressure
or decreased tissue perfusion stemming from impaired circulatory
regulation is attractive and merits further investigation.
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Orthostatic Intolerance in Adolescent CFS is
consistent with the Postural Tachycardia Syndrome
Upright posture is, along with exercise, one of
two fundamental human stressors requiring rapid and effective
circulatory and neurologic compensations in order to maintain
blood pressure, cerebral blood flow, and consciousness. The
physiology of upright posture is unique to hominids and cannot be
easily studied in animals. Recent investigations lend credence to
the hypothesis that CFS results at least in part from low upright
blood pressure by strongly implicating neurally mediated
hypotension (NMH), a form of orthostatic intolerance, in the
symptomatology of chronic fatigue syndrome in adults. In their
landmark observations, Rowe and coworkers produced NMH in twenty-one
of twenty-two patients with CFS using head-up tilt (HUT), a
standard orthostatic maneuver which rapidly produces enhanced
sympathetic tone while decreasing parasympathetic tone in normal
subjects. An earlier work, however, reported somewhat different
findings in adolescents with CFS who had tachycardia often
associated with hypotension during orthostasis. This is the
orthostatic tachycardia syndrome described at least since 1940
under many aliases. Recently the syndrome has undergone a
renaissance as the "postural orthostatic tachycardia
syndrome", acronymically "POTS", reported in
adults by workers at the Mayo clinic and also as the syndrome of
chronic orthostatic intolerance reported by the Vanderbilt group.
We reported the first pediatric cases of POTS. Our data has shown
that the pattern of orthostatic intolerance during HUT in the
adolescents with CFS is predominantly POTS.
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Chronic Fatigue Syndrome