Chronic Inflammatory Demyelinating Polyneuropathy: Muscle Atrophy Associated with Denervation and Neuromuscular Transmission Instability

Abstract

IntroductionChronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired neuropathy of immunological origin. Increased understanding of the pathophysiology of CIDP is of specific interest due to the treatable nature of the disease. It is characterized, in most cases, by symmetrical weakness in proximal and distal muscles that progresses for greater than 2 months. Evidence indicates that disease‐related post‐synaptic damage and muscle fiber atrophy lead to neuromuscular junction remodeling and impaired neuromuscular transmission (Deschenes et al. 2011). The integrity and stability of neuromuscular transmission can be examined using decomposition‐based quantitative electromyography (DQEMG), which can assess the degree of variability in the shape of consecutively detected motor unit potentials (MUPs) termed ‘jiggle’. In this study we compared voluntary and stimulated contractile function, electrophysiological motor unit (MU) properties and muscle volume quantities in a group of CIDP patients (n=11) with a group of age and sex‐matched healthy controls (n=11).MethodsIn an isometric dynamometer, dorsiflexion strength with twitch interpolation to assess voluntary activation, was recorded. Surface and concentric needle electromyographic (EMG) signals were collected from the tibialis anterior (TA). Compound motor action potentials (CMAPs) for the TA were obtained by supra‐maximal stimulation of the fibular nerve. To estimate the number of MUs in the TA the decomposition enhanced spike‐triggered averaging technique was applied. This required subjects to contract at 25% of their maximal voluntary strength for a series of 30s contractions until at least 20 suitable MU trains were acquired. From the intramuscular needle‐detected signals of single MUs, neuromuscular transmission stability was assessed through calculation of MUP ‘jiggle’. Magnetic resonance imaging (MRI) was used to calculate TA muscle volume.ResultsDespite near maximum voluntary activation (~98%), CIDP patients were ~50% weaker and had ~60% lower CMAP amplitudes than controls. The estimated number of functioning MUs in the TA was ~30% fewer in CIDP and with ~68% higher ‘jiggle’ values indicative of greater neuromuscular transmission instability. MRI results indicated that CIDP patients had ~40% less muscle volume in the TA compared to controls. From these preliminary results, those with CIDP have less strength, but are highly activated. They have substantially lower CMAP values and fewer numbers of MUs compared with controls. Neuromuscular stability is also considerably lower in CIDP.ConclusionsVoluntary muscle weakness appears multifactorial and is due to limitations of peripheral neuromuscular transmission, muscle atrophy and moderate MU loss. MRI data indicate atrophy of the TA muscle in CIDP subjects who exhibit approximately half the muscle mass of controls. These measures that detect MU loss, neuromuscular transmission instability and muscle atrophy could be useful for objective assessment of disease severity leading to improved ability to monitor disease progression and treatment outcomes. Furthermore the use of DQEMG could be incorporated into larger studies to help identify CIDP patients in the early stages of neuromuscular degeneration allowing for earlier and perhaps more effective intervention.Support or Funding InformationSupported by NSERC.