Intensive Care Unit-Acquired Weakness: Neuropathology.

There is extensive evidence in the literature that both peripheral nerve fibers and muscle fibers are affected in the course of intensive care unit-acquired weakness. Peripheral nerve lesion is characterized by axonal degeneration, without inflammatory changes. Muscle fiber involvement is characterized by muscle fiber atrophy and loss of thick filaments, predominantly involving type 2 fibers, but myonecrosis ("acute necrotizing myopathy of intensive care") has also been reported. Steroids can precipitate thick myofilament damage, probably to some extent also triggered by immobilization and neuromuscular junction blockade. Sepsis and a systemic inflammatory response cause muscle fiber injury because of the release of cytokines and chemokines that modulate enzymatic reactions related to proteolysis. Regarding axonal injury, hyperglycemia, hypoalbuminemia, inflammatory response, and hypoperfusion are accepted risk factors. Nerve and muscle biopsy are the best methods for detection of structural abnormalities, but these are invasive investigations; although not suitable for repeated studies, in selected cases, biopsies may have a role in diagnosis.