Electrophysiological investigations of peripheral nerves and muscles: a method for looking at cell dysfunction in the critically ill patients

Excerpt

Resting trans-membrane potential difference (E_m) of skeletal muscle is correlated to the energy status of the organism: the more severe the illness, the lower the E_m. In 1971, Cunningham demonstrated this association with severely debilitating medical conditions, showing an increase in intracellular sodium concentration possibly due to a “generalized cellular abnormality” [1]. The study posed the basis for considering local (muscle) bio-electrical events generated by excitable tissues as indicative of the well-being of the entire organism. In 1995, Leijten showed that patients with electrophysiological signs of polyneuropathy had increased intensive care unit (ICU) mortality, more prolonged rehabilitation, and persistent 1-year motor handicap than those without [2]. In 1996, Latronico demonstrated normal nerve histology, despite electrophysiological findings of axonal neuropathy, in biopsies taken in the early stage of acute disease. In late biopsies, however, axonal nerve degeneration was evident [2]. This generated the hypothesis that functional (electrical) impairment may precede structural (histologic) changes and that electrophysiological study (EPS) might be used to look indirectly but non-invasively at cell functioning. During sepsis, a prototypical low-energy hyper-catabolic state, the nerves were trying to maintain their structure and survive by reducing or abolishing the function, a phenomenon easily documented by EPS. If sepsis persisted, the energy supply and/or use might not be restored and the histologic alterations would eventually ensue. According to this theory of the bioenergetic failure, “stunned but still living peripheral nerves and muscles may serve as a sentinel for the development of multiple organ dysfunction syndrome” [3]. In 1999, Hotchkiss described a similar divergence between in vivo clinical evidence of organ failure and post-mortem histologic absence of extensive organ damage sufficient to explain the morbidity and mortality of sepsis [4]. They also hypothesized that in situations of energy failure the cells may revert to a low energy state, a “hibernation” of the cell, to avoid cell death. The theory received support from two multi-center clinical studies, CRIMYNE [5] and CRIMYNE-2 [6], showing that the peroneal nerve, a long lower limb motor nerve, was the most commonly affected nerve. The axons are devoid of the machinery for biosynthetic processes, and all axonal components are synthesized in the cell body. Their anterograde transportation to the nerve terminal requires considerable energy expenditure and may fail if the nerve does not receive adequate nourishment [5]. …