Nerve excitability changes after intravenous immunoglobulin infusions in multifocal motor neuropathy and chronic inflammatory demyelinating neuropathy

Abstract 

Intravenous immunoglobulin (IVIg) infusions may provide clinical benefits in multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP). The short delay in the clinical response to IVIg therapy is not consistent with a process of remyelination or axonal regeneration. We assessed whether or not the efficacy of IVIg infusions in MMN and CIDP could reflect changes in axonal membrane properties and nerve excitability. Ulnar motor nerve excitability was studied before and after three to five consecutive days of IVIg infusions (0.4g/kg/day) in 10 patients with MMN, 10 patients with CIDP, and 10 neurological controls (CTRLs). Excitability recovery cycle, stimulus–response and strength–duration properties were investigated. The recovery cycle parameters (absolute and relative refractory period durations, refractoriness and supernormality) were similar in all groups and did not change after IVIg infusions. At baseline, patients with CIDP, but not with MMN, showed a reduced strength–duration time constant (chronaxie) and increased rheobase when compared to CTRLs. After IVIg infusions, strength–duration time constant remained stable in CTRLs, but decreased in patients with MMN or CIDP. Rheobase increased in the three groups after treatment. The decreased strength–duration time constant after IVIg infusions in patients with MMN or CIDP could reflect a reduction of persistent Na⁺ current, able to limit intraaxonal Na⁺ accumulation and then to produce neuroprotective effects. However, this could also reflect compensatory mechanisms that did not directly underlie the therapeutic effect. Whatever the underlying process, this result revealed that IVIgs were able to produce early nerve excitability changes.

Keywords: Chronic inflammatory demyelinating polyneuropathy, Conduction block, Intravenous immunoglobulin, Multifocal motor neuropathy, Rheobase, Sodium conductance, Strength–duration time constant, Supernormality