The discovery of critical illness polyneuropathy
Sepsis originally meant putrefaction, a decomposition of organic matter. Pasteur and Koch discovered that the decomposition was due to micro-organisms. In his famous textbook of medicine published in 1892 , Osler observed ‘rapid loss of flesh' with prolonged sepsis. For many years this rapid loss of flesh was attributed to a catabolic myopathy, and respiratory muscle weakness, to diaphragmatic fatigue. In 1961 Mertens  described ‘coma-polyneuropathies' in patients who had circulatory shock associated with acute intoxication and severe metabolic crises, seemingly due to metabolic and ischaemic lesions of the peripheral nervous system. In 1971 Henderson and colleagues  described a polyneuropathy in patients with burns.
Beginning in 1984 Bolton and colleagues reported a series of studies [4-7] defining the clinical, electrophysiological and morphological manifestations of critical illness polyneuropathy, a primary distal axonal degeneration of motor and sensory fibres. The authors suggest that the polyneuropathy was due to the ‘toxic' effects of sepsis itself. In many patients polyneuropathy was accompanied, or preceded, by septic encephalopathy (both encephalopathy and polyneuropathy occurring in approximately 70% of septic patients) [8,9]. With successful treatment of the sepsis, encephalopathy often cleared rapidly only to be replaced by critical illness polyneuropathy. This often presented as the difficulty in weaning from mechanical ventilation when cardiac and pulmonary causes had been excluded . Clinical signs of polyneuropathy were present in only half of the patients who were shown by electrophysiological studies to have polyneuropathy. During this time similar cases of polyneuropathy were reported from several countries throughout the world .
The more recent literature has been dominated by reports of paralysis in the ICUs that were presumed complications of neuromuscular blocking agents and steroids . Many of these patients have sepsis as a prominent underlying factor. This myopathy takes several forms. Cachectic myopathy is difficult to identify in clinical situations. In patients in the post-transplant state or with acute severe asthma, who are treated with neuromuscular blocking agents and steroids, the myopathy shows a distinctive deficiency of myosin on biopsy. In other patients the biopsy findings are dominated by varying degrees of necrosis that, if severe, tend to harbour a poor prognosis, termed the acute necrotizing myopathy of intensive care . Lacomis and colleagues  have recently proposed the designation for these different types of myopathy under the umbrella of critical illness myopathy.
In an important study Latronico and colleagues  described patients in the ICU, who had a severe critical illness polyneuropathy and myopathy. It supported the concept that sepsis has severe effects on both nerve and muscle. Moreover, their studies indicated that functional changes preceded structural changes. This group also identified in nerve biopsies enhanced expression of E-selectin in the vascular endothelium, this adhesion molecule perhaps mediating disturbances of the microcirculation to peripheral nerve .
de Letter and colleagues  have shown that assessment of Apache III, a quantitative index of disease severity, and the presence of the systemic inflammatory response syndrome (severe sepsis), both predicted the later development of critical illness polyneuropathy and myopathy.
While there is still no specific treatment for critical illness polyneuropathy, van den Berghe and colleagues  have reported that intensive insulin therapy in critically ill patients, possibly through stimulating peripheral glucose uptake and restoring abnormal lipid profiles, significantly reduces the incidence of critical illness polyneuropathy.
If the sepsis and multiple organ failure can be brought under control, varying degrees of recovery from critical illness polyneuropathy can be expected to occur. However, if the polyneuropathy is unusually severe, recovery may not occur.
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