The effects of Chronic Inflammatory Demyelinating Polyneuropathy on the Neuromuscular System in Humans
Abstract
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is an inflammatory autoimmune peripheral nerve disorder. CIDP is associated with demyelination, slow motor nerve-conduction velocity, and distal muscle weakness. CIDP is under-recognized due to its heterogeneous presentation and the limitations of clinical diagnostic criteria. Using a combination of electrophysiology and muscle imaging techniques the four studies outlined in this thesis systemically investigate the impacts of this demyelinating disease on motor nerves and their innervated muscles.
The first two studies examine the neuronal consequences of demyelination caused by CIDP and the following two studies investigate how skeletal muscle is affected by these neuronal complications. Specifically, the purpose of study 1 was to investigate whether patients with CIDP demonstrate motor unit loss, and to determine the neuromuscular transmission stability of motor units. Results showed patients with CIDP have reduced motor unit number estimates (MUNEs), in addition to motor unit instability and transmission blocking in the tibialis anterior (TA) muscle. The purpose of study 2 was to investigate modifications to motor unit discharge characteristics of affected motor units. The results indicate CIDP leads to axonal or neuromuscular block and abnormally high motor unit firing rates of early recruited motor units as a compensatory mechanism to mitigate the frank neuronal loss in the TA.
The purpose of studies 3 and 4 was to assess the consequences of peripheral axon loss and motor unit instability on muscle quality and quantity in patients with CIDP. It is critical to investigate whether these neuronal changes precipitate uniform alterations in musculature. Study 3 showed that patients with CIDP have less overall muscle mass and more non-contractile tissue infiltration in the TA of the anterior leg compartment. Study 4, demonstrated that muscles in the posterior leg compartment, that differ functionally from the TA and are innervated by a different portion of the sciatic nerve undergo similar morphological changes to the TA. In combination, these neuronal deficits and skeletal muscle structural abnormalities likely lead to muscle weakness and functional impairment seen in patients with CIDP. Together these studies form a foundational understanding of how CIDP impacts both nervous and muscle tissue at a systems level.