Post-polio syndrome pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Pathophysiology
Several theories have been proposed to explain post-polio symptoms. One theory of the mechanism behind the disorder is that it is due to "neural fatigue" from overworked neurons. The original polio infection generally results in the death of a substantial fraction of the motor neurons controlling skeletal muscles, and the theory is that the remaining neurons are thus overworked and eventually wear out.
Another theory holds that the original viral infection damages portions of the lower brain, possibly including the thalamus and hypothalamus. This somehow upsets the hormones that control muscle metabolism, and the result is a metabolic disorder similar to mitochondrial disorder that causes muscle pain and injury (via rhabdomyolysis) and also causes the fatigue. Some also believe that the original polio caused the atrophying of some muscles and as the person ages the weakness caused by loss of muscle mass due to aging is accelerated due to the person starting off with less muscle. Another possibility is that post-polio symptoms are due to some combination of mechanisms.
Neural fatigue
The most widely accepted theory is the "neural fatigue" one. Motor neuron fibers were originally damaged by the polio virus and were subsequently over-stressed because too few surviving neurons activated too many muscles. Eventually these neurons become fatigued and die, leading to the slowly advancing loss of muscle function that is typical of post-polio. This scenario may be accelerated by the fall-off in production of nerve growth factor (NGF) that occurs with menopause/andropause.
Mitochondrial disruption
This theory assumes that the major symptoms of PPS are a result of some interference with the action of mitochondria in the muscles and possibly the nerves. Failure of the mitochondria to produce sufficient energy would result in the muscle pain typical of PPS, and would, over time, cause muscle death (rhabdomyolysis) due to exerting the muscle beyond its ability to recover. The cause of this interference with mitochondrial action is presumably a change in the body's hormone balance, as mediated by the hypothalamus and other lower brain areas that control hormones (and which were, presumably, damaged by the original polio virus infection). As with the neural fatigue theory, menopause/andropause accelerates the process, though this time by most likely disrupting the NOTCH pathway that controls cell differentiation and damage repair.
One significant argument in favor of the mitochondrial disruption theory is that it explains the fatigue and cognitive difficulties ("brain fog") symptoms that usually accompany post-polio better than the neural fatigue theory does.
Reticular activating system damage
Damage to the reticular activating system and related areas such as the thalamus can also produce most of the fatigue, "brain fog", and dysautonomia symptoms of post-polio, and may be able to cause hormonal changes that result in progressive muscle weakness. Post-mortem examinations of polio patients have shown damage to these areas, and some PPS patients show lesions in these areas when examined by MRI. Many authorities believe that these areas are damaged by the initial polio infection, either as a direct result of the polio virus, or due to an autoimmune reaction following the polio infection.
One problem with this theory, though, is that it doesn't easily explain the delayed onset of PPS. It may be that this theory needs to be combined with one of the others to explain delayed onset.
Mechanical overwork
The stresses placed on nerves, muscles, and joints in a polio survivor are in many cases several times those experienced by other people. Problems with gait, in particular, can greatly over-stress joints and the surviving muscles, and the polio survivor is also likely to compensate for weakened arms by jerking more when lifting/pulling something. Over time (and again with menopause/andropause), this results in fatigue and damage.
Reactivated polio
An early theory stated that PPS is caused by reactivation of latent polio virus in the body, similar to the way that shingles is a reactivation of the chicken pox virus. This theory has been discredited by laboratory studies that show no active polio virus in the body.