Measuring and modeling of axon membrane properties in motor neuron disorders and normal subjects

In this thesis we present our research on two disorders of motor neurons: amyotrophic lateral sclerosis (ALS) and multifocal motor neuropathy (MMN). Amyotrophic lateral sclerosis (ALS) presents with muscle weakness, respiratory failure, and severe decrease of life expectancy. The symptoms develop due to upper and lower motor neuron loss of undefined reasons. No treatment, preventing austere invalidation in ALS, has been developed yet, but some novel therapies are currently approbated. Clinically ALS may overlap with MMN, a rare, chronic, immune-mediated neuropathy. MMN is a slowly progressive disease which does not affect patient longevity and is characterized by asymmetric weakness and atrophy of limb muscles. In MMN lower motor neurons in peripheral nerves are affected due to degeneration or multifocal loss of their myelin sheath. MMN is considered an immune-mediated neuropathy since in approximately half of the patients serum antibodies against ganglioside GM1 are found and administration of immunoglobulins induces improvement of muscle strength. The treatment effect is only temporary so that repeated administration is required. Despite treatment, muscle strength and loss of motor axons slowly progresses. Since functioning of the neuromuscular system depends on membrane properties of the axon, defined as nerve excitability and provided by ion channels and pumps, recording their activity would offer a unique chance to non-invasively evaluate the role of axonal membrane properties in specific clinical features of MMN and ALS and to assess the effect of medication on the axon in these disorders, where altered excitability was previously shown. Our study demonstrates the significance of implementing excitability testing both in scientific and clinical research of the motor neuron disorders, as it offers the possibility to assess the activity of axonal voltage-gated ion channels and sodium-potassium pump; to compare axon membrane properties in different types of axons; to explore nerve excitability in single motor units; to evaluate the disease progression where other techniques are not powerful enough; and to monitor the treatment effect.