Reinnervation and Neuromuscular Transmission in ALS

Reinnervation,Blood biomarkers,Fatigue and decrement

The aim of this study is to describe the changes in the neuromuscular connection in patients
 with amyotrophic lateral sclerosis (ALS). The study consist of three substudies that have the
 following main hypothesis:
 
 1. that ALS patients do not demonstrate equal capacity for muscle reinnervation and that
 reinnervation preserves muscle function and thereby slows down progression.
 
 2. that blood concentrations of c-terminal agrin fragment (bCAF) reflect neuromuscular
 transmission deficiency and that blood concentration of neural cell adhesion molecule
 reflects degree of muscle denervation in patients.
 
 3. that ALS patients with decrement when examined with repetitive nerve stimulation have
 more physical fatigue, slower progression, higher degree of reinnervation and higher
 bCAF compared to ALS patients without decrement.
 
 There will be 3 inclusion groups.
 
 1. patients referred for neurophysiological examination on suspicion of motor neuron
 disease.
 
 2. healthy controls
 
 3. disease control: patients with another motor neuron disease with slow progression.
 
 All participants will be invited for at least 1 visit (baseline). If participants in group 1
 eventually receive the diagnosis of ALS they will be invited for 2 additional visits 4 og 8
 months after baseline visit, respectively.
 
 Examinations will consist of:
 
 - nerve conduction study
 
 - repetitive nerve stimulation (except for healthy controls) to examine impairment of the
 neuromuscular connection.
 
 - motor unit number estimation with MScanFit to estimate number and size of motor units.
 
 - ultrasound examination of muscles to measure size and condition of muscles.
 
 - questionnaires on fatigue and functional status.
 
 - blood sample for measurement of specialized analysis (c-terminal agrin fragment and
 neural cell adhesion molecule) and routine analysis (liver and kidney function as well
 as neurofilament light chain)
 
 - muscle strength assessment manually and by dynamometer to follow progression of muscle
 weakness
 
 - bioelectrical impedance measurement to follow the overall body composition.