Adverse effects of myasthenia gravis on rat phrenic diaphragm contractile performance

Abstract

Adverse effects of myasthenia gravis on rat phrenic diaphragm contractile performance.

Deficits in Endogenous Adenosine Formation by Ecto‐5′‐Nucleotidase/CD73 Impair Neuromuscular Transmission and Immune Competence in Experimental Autoimmune Myasthenia Gravis

“…Considering that the reduced skeletal muscle strength during repetitive nerve stimulation reflects the neuromuscular/immunological imbalance operating in EAMG, we performed myographic recordings using diaphragm preparations stimulated indirectly via the phrenic nerve trunk under fatigue conditions. These were produced by high-frequency (50 Hz) intermittent (17 pulses per sec, during 3 minutes) phrenic nerve stimulation [ 17 ]. Figure 1(d) shows that muscle fatigue was significantly ( P < 0.05) more intense in EAMG animals than in both naïve and control littermates.…”

“…Pulses were generated by a Grass S48 (USA) stimulator coupled to a stimulus isolation unit (Grass SIU5) operating in a constant current mode. Tetanic failure (fatigue) of hemidiaphragm muscle contractions was achieved using high frequency (50 Hz) intermittent (17 pulses per sec, during 3 minutes) nerve stimulation [ 17 ]. The percentage of contractile reduction force was calculated by assessing the percentage of variation of the peak force at the last train (applied at 180 seconds of stimulation) comparatively to the peak force observed at the beginning of the intermittent stimulation.…”

A Diagnostic and Management Dilemma

“…As a result of the occurrence of immune events before the clinical manifestation of the autoimmune disease, dissimilar adaptive mechanisms of the immune system and differences in immunogenicity of the autoimmune disorders, patients with "false positive autoantibodies" develop clinical symptoms "with a risk factor that exceeds the overall rate of the disease among the general population by a factor of no less than forty." 11,39,[47][48][49][50][51][52][53][54][55][56][57][58] Thus, patients with evidence for biologic coexistence of autoimmune diseases may have antibody marker(s) for an occult immune disorder(s), which may not clinically become evident until the threshold necessary to overcome the function of the host antigenic target is reached. As a result, patients with biologic coexistence of MG and LEMS may not constitute a distinct clinical picture in their own right.…”

Sleep and Neuromuscular Disease

“…46,48,50 Many studies also found that sleep disordered breathing did not correlate with MG severity, although it may be less common in ocular MG. 46,48,49,51 Selective impairment of diaphragm function, even in the absence of grossly affected limb strength, might explain this. 48,[52][53][54][55] Despite suggestions in the older literature, there is no evidence for CNS involvement in MG, as anti-AChR antibodies, even if they did cross the blood-brain barrier, do not cross-react with antigenically different CNS nicotinic AChRs. 56,57 Myotonic Dystrophy Myotonic dystrophy is an autosomal dominant hereditary muscle disorder with unstable trinucleotide CTG repeats in the gene for protein kinase on chromosome 19.…”