No abstract

The acute motor axonal neuropathy (AMAN) form of the Guillain-Barre syndrome is a paralytic disorder of abrupt onset characterized pathologically by motor nerve fiber degeneration of variable severity and by sparing of sensory fibers. There is little demyelination or lymphocytic inflammation. Most cases have antecedent infection with Campylobacter jejuni and many have antibodies directed toward GM1 ganglioside-like epitopes, but the mechanism of nerve-fiber injury has not been defined. In 7 fatal cases of AMAN, immunocytochemistry demonstrated the presence of IgG and the complement activation product C3d bound to the axolemma of motor fibers. The most frequently involved site was the nodal axolemma, but in more severe cases IgG and C3d were found within the periaxonal space of the myelinated internodes, bound to the outer surface of the motor axon. These results suggest that AMAN is a novel disorder caused by an antibody- and complement-mediated attack on the axolemma of motor fibers.

The localization, mode of action, and roles of complement in the Guillain-Barre syndrome have been controversial. We used high-resolution immunocytochemistry to localize complement activation products in early stages of the acute inflammatory demyelinating polyneuropathy (AIDP) pattern of Guillain-Barre syndrome. Three AIDP subjects who were autopsied had had symptoms for 3 to 9 days at the time of death. Immunocytochemistry was performed on etched, epoxy resin-embedded sections, and the next thin section was compared by electron microscopy (thick/thin sections). Many fibers had a rim of the complement activation marker C3d and the terminal complement complex neoantigen C5b-9 along the outer surface of the Schwann cells. Ultrastructural analysis of these C3d-positive fibers showed mild vesicular changes of the outermost myelin lamellae. Vesicular degeneration was seen before the invasion of macrophages into the myelin, and was the predominant change in the subject with symptoms for 3 days. C3d staining was not found on myelin membranes. The results suggest that at least some forms of AIDP are complement mediated. We speculate that complement is activated by antibody bound to epitopes on the outer surface of the Schwann cell and that the resulting complement activation initiates the vesiculation of myelin.

Stroke patients have profound cardiovascular and muscular deconditioning, with metabolic fitness levels that are about half those found in age-matched sedentary controls. Physical deconditioning, along with elevated energy demands of hemiparetic gait, define a detrimental combination termed diminished physiological fitness reserve that can greatly limit that can greatly limit performance of activities of daily living. The physiological features that underlie worsening metabolic fitness in the chronic phase of stroke include gross muscular atrophy, altered muscle molecular phenotype, increased intramuscular area fat, elevated tissue inflammatory markers, and diminished peripheral blood flow dynamics. Epidemiological evidence further suggests that the reduced cardiovascular fitness and secondary biological changes in muscle may propagate components of the metabolic syndrome, conferring added morbidity and mortality risk. This article reviews some of the consequences of poor fitness in chronic stroke and the potential biological underpinnings that support a rationale for more aggressive approaches to exercise therapy in this population.