Post-Polio Syndrome

Post-polio syndrome (PPS) refers to a clinical condition that affects polio survivors’ years after the initial polio onset and has sequelae. PPS is a progressive neuromuscular syndrome characterized by weakness, fatigue, muscle and joints pain, and difficulty breathing and swallowing.

Pathophysiology of PPS

Humans are the only hosts for the poliovirus. PPS is associated with death or structural and functional impairments of the expanded surviving motor units. The virus specifically targets motor neurons in the anterior horn cells of the spinal cord and brainstem. Its proliferation leads to the death of affected motor neurons. Secondly, the adjacent motoneurons re-innervate isolated muscle fibers that are lost to acute poliomyelitis infection, forming huge motor units. However, the mechanism of these dysfunctions is not clear, and the following hypotheses have been proposed:

• Persistent genetic viral material can stimulate and deactivate inflammation and immune system response in the central or peripheral nervous system.
• An imbalance in the physiological processes of expanded motor units degeneration and regeneration.
• Abnormal muscle fiber structure and function and/or sensorimotor integration.

Fig.1 Pathophysiological changes seen with acute poliomyelitis. (Gawne, 1995)

Mechanism of Infection

A distinctive characteristic of acute polio infection is the predilection of the poliovirus for the nerve cells that control muscles. These nerve cells or motor neurons are composed of cell bodies located in the anterior horn of the spinal cord and a long tentacle, or axon extending to the muscles. With uncanny precision, the poliovirus invades the motor neurons, leaving intact adjacent nerve cells that control the functions of sensation, bowel, bladder, and sex. The poliovirus typically infects more than 95% of the motor neurons in the spinal cord and many other cells in the brain. The infected cells either overcome the virus or die.

There is a growing consensus among researchers that PPS involves a slow degeneration of the terminal axon sprouts that innervate the muscle cells. The progressive lesion occurs when the normal regeneration of the sprouts from the axon to the muscles is interrupted and malfunctioning sprouts are not replaced. This interruption of the repair process produces irreversible, progressive muscle weakness. The fluctuating lesion, on the other hand, is thought to be caused by defective synthesis or release of the neurotransmitter acetylcholine. Scientists have demonstrated that muscle weakness and fatigue can be reversed in some patients with PPS by the drug pyridostigmine, which enhances the effectiveness of acetylcholine in triggering muscle contractions. Other researchers are testing another class of agents known as nerve growth factors, which stimulate both nerve and muscle cell growth.

Possible Causes of PPS

Degeneration of the axon sprouts can explain the new muscle weakness and fatigue, but what causes the degeneration in the first place remains a mystery. The most plausible hypothesis proposes that muscle weakness is simply the result of the overuse of individual motor neurons over time. In addition, some researchers report that some motor neurons in the anterior horn of the spinal cord of polio survivors appear to be smaller than normal. It is believed that these smaller motor nerve cells were somehow damaged at the time of the acute polio infection and that they are vulnerable to premature failure.

Fig.2 Putative factors in the etiology of generalized fatigue in post-polio syndrome. (Li, 2019)

Attrition of motor neurons because of aging alone, however, may not be a significant factor in PPS. Persistence of the poliovirus in the body - or, more precisely, viral particles that have lain dormant for many years and then are reactivated by some unknown mechanism - may also play a role. Other causes of PPS, such as an immune-mediated response, hormone deficiencies, and environmental toxins, have also been proposed.

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References

1. Gawne, A.C.; Halstead, L.S. Post-polio syndrome: pathophysiology and clinical management. Critical Reviews in Physical and Rehabilitation Medicine. 1995, 7(2).
2. Li, H.S.S.; et al. Post-polio syndrome: more than just a lower motor neuron disease. Frontiers in neurology. 2019, 10: 773.