To Home Page of PHI website to PHI's Secure Shopping Cart
PHI's Education
About PHI Education Advocacy Research Networking to How to Donate to Membership Application

Post-Polio Health (ISSN 1066-5331)

Vol. 14, No. 4, Fall 1998
Presented at Seventh International Post-Polio
and Independent Living Conference,
Saint Louis, Missouri, May 29-31, 1997:

Post-Polio Motor Neurons and Units: What We Know for Sure

Neil R. Cashman, MD, University of Toronto, Toronto, Canada

Motor neurons are located in the brainstem and spinal cord. They send long processes called axons out to the muscle. In the muscle, the axon divides into terminal axonal branches that contact muscle fibers to trigger their contraction. The terminal axons communicate with the muscle fibers at the neuromuscular junction through release of acetylcholine, a chemical compound synthesized by motor neurons.

A normal motor neuron innervates from a few to thousands of muscle fibers, depending on the muscle. An eye muscle, for example, needs few muscle fibers compared with a leg muscle that may need up to 5,000 muscle fibers per motor neuron. A motor unit is defined as a motor neuron and all the muscle fibers it supplies.

Part of the recovery process from acute poliomyelitis involves terminal axonal sprouting of remaining healthy motor neurons to reinnervate muscle fibers that have become denervated by destruction of their motor neurons. These axonal sprouts can dramatically increase the number of muscle fibers innervated by the same motor neuron - in some cases, as many as seven to eight times normal.

This arrangement, good as it is over the short term, is not indefinitely stable. Over time, muscle fibers begin to lose their innervation. Imagine, for example, a tree trunk with many branches that has eight or nine times as many branches grafted onto it. The tree may be able to support those extra branches for a period of time, but eventually they may begin to degenerate or fall off. This process is what we think is going on in post-polio syndrome, first proposed by David Wiechers, MD, and Susan Hubble, MD, in 1981.

What evidence do we have that supports that hypothesis? Muscle biopsies provide the strongest indication that there is some ongoing, terminal axonal degeneration. But listening over the years to people having this problem, my colleagues and I have concluded that post-polio syndrome is not simply a disease of slowly progressive new weakness.

We have proposed that the complaints – fatigue, lack of endurance and a whole list of other symptoms originally collated by Mary Codd, MD, when she was doing her work with Anthony Windebank, MD, at the Mayo Clinic - that wax and wane and can change from hour to hour or day to day or week to week are due to dysfunction in terminal axons rather than degeneration.

If a terminal axon is in the process of degenerating, it is not here one day and gone the next. During an intervening period, the axon is not functioning 100%, but it is still there.

What is the evidence of axonal dysfunction? Electromyography can demonstrate a muscle that has been stimulated very rapidly, but then loses its force into the stimulation. If we stopped and waited a couple of minutes, the muscle would restart at this high level, and we could show a decline with the stimulation of the whole muscle. Single-fiber EMG demonstrates the phenomenon called jitter, and increased jitter is a measure of dysfunction of terminal axons.

We can also use a stain for a special molecule called neural cell adhesion molecule. When muscle fibers are happy, when they are appropriately and correctly supplied by nerve fibers, they suppress production of this molecule. When they are unhappy, when their nerve fibers are not communicating with them, they express this molecule. We can see staining in 10-15% of the fibers, strongly suggesting that a large proportion of the muscle fibers are unhappy. They are not getting the proper connection with the nerve fiber.

Finally, in a series of experiments done by my colleague, Daria A. Trojan, MD, MSc, we broke down neuromuscular transmission with increasing rates of stimulation, in a technique called stimulation single-fiber EMG. With increasing rates of stimulation, there is increasing jitter indicating a defect in the transmission between the nerve and the muscle.

Thus, we have many lines of evidence to strongly suggest that the terminal axon is dysfunctional. It is not functioning properly on its road to complete degeneration. There is an intervening period of dysfunction, which may last for weeks to years.

Dr. Trojan and I have determined that part of the terminal axon dysfunction is due to a defect in the release of acetylcholine. An increase in acetycholine may reduce fatigue and fatigueability and may increase strength. In an open drug trial of Mestinon (pyridostigmine) in 1994, we measured fatigue in people with post-polio syndrome, and found a reduction in fatigue in the people taking Mestinon. In 1997, the North American Post-Poliomyelitis Pyridostigmine Study (NAPPS) found that Mestinon did not provide significant benefits with respect to quality of life, fatigue or isometric muscle strength compared to a placebo, although a trend was noted towards increased strength in very weak muscles.

We know there is terminal axonal degeneration. We also believe strongly that there is terminal axonal dysfunction not readily treated. We may be able to support the function of a terminal axon for years or decades, once we know why they are dysfunctional and how we can effect an improvement in this process.