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The clinical entity critical illness polyneuropathy occurs almost exclusively in patients in critical care units and has been characterised as a complication of sepsis and multiple organ failure.1 2 Critical illness polyneuropathy may be a common cause of the difficulty in weaning patients from the ventilator, particularly those who show intractable ventilator dependence. All the measures used to prevent or treat sepsis and multiple organ failure are the main methods now used to deal with critical illness polyneuropathy. Knowledge of this type of polyneuropathy is of help in making decisions about respirator techniques, nursing care, prognosis, and overall management. Moreover, recognition of critical illness polyneuropathy indicates the need for physiotherapy, rehabilitation, and other supportive measures as the patient recovers. Boltonet al 1 have made an important positive contribution to the care of patients with critical illness polyneuropathy. The actual aetiology, however, has yet to be determined. The pathogenesis needs to be clarified to treat patients more effectively.
Critical illness polyneuropathy invariably occurs at the peak of critical illness and sepsis, but in Guillain-Barré syndrome there is a brief period of recovery after a relatively minor illness or inoculation. Except for differences in the predisposing causes, as Bolton et al 1 reported, it is difficult to distinguish critical illness polyneuropathy from Guillain-Barré syndrome on purely clinical grounds. In both, polyneuropathy runs a monophasic course, the onset being relatively acute but with subsequent improvement in most instances. The clinical features also are similar; evidence of muscle weakness in all four limbs, occasional involvement of facial muscles and frequent involvement of the muscles of respiration, the depression or absence of deep tendon reflexes, and some evidence of distal sensory impairment.
The first step by Bolton et al 1in determining exact aetiology was to differentiate critical illness polyneuropathy from Guillain-Barré syndrome. In reviewing the patients with critical illness polyneuropathy and Guillain-Barré syndrome who were studied in their EMG laboratory, they found marked differences between the two types of polyneuropathy. Patients with Guillain-Barré syndrome had greater slowing of the speed of impulse conduction, and, in the initial stages, abnormal spontaneous activity in the muscle was absent, indicative of a predominantly demyelinating polyneuropathy. The CSF was only mildly increased in patients with critical illness polyneuropathy, but it was much increased in patients with Guillain-Barré syndrome. Comprehensive studies done at necropsy and nerve biopsies of patients with critical illness polyneuropathy showed the presence of primary axonal degeneration of the motor and sensory fibres, mainly distally, with no evidence of inflammation.2 Zochodne et al(including Bolton) therefore concluded that the two types of polyneuropathies most probably are separate entities.
Guillain and colleagues enumerated the clinical and spinal fluid features of one form of acute flaccid paralysis without regard for the underlying physiology or pathology. Classic pathological studies of Guillain-Barré syndrome, however, have identified prominent demyelination and inflammatory infiltrates in the spinal roots and nerves. Guillain-Barré syndrome often has been considered to be synonymous with the pathological designation of acute inflammatory demyelinating polyneuropathy, and physiological abnormalities consistent with demyelination have been taken as supportive evidence for the diagnosis of Guillain-Barré syndrome. Feasbyet al (with Bolton)3 first called attention to patients who were clinically considered as having Guillain-Barré syndrome, but who were characterised electrophysiologically as having early axonal degeneration of the motor and sensory nerve fibres. The evidence included a rapid fall in compound muscle action potentials and sensory nerve action potentials, and no evidence of demyelination. Such patients often had severe paralysis and made a slow recovery, presumably reflecting the need to regenerate axons rather than remyelination. Pathological findings are consistent with axonal degeneration without demyelination. Feasbyet al 3 termed this pattern axonal Guillain-Barré syndrome and suggested that there is a fundamental difference in the underlying pathophysiology, resulting in primary axonal damage rather than demyelination. Griffinet al 4 then confirmed the existence of the acute motor-sensory axonal neuropathy (AMSAN) pattern of Guillain-Barré syndrome described by Feasby et al.3
Infection caused by the gram negative bacteriumCampylobacter jejuni, a leading cause of acute diarrhoea, commonly precedes the development of Guillain-Barré syndrome.5 There is a close association between axonal Guillain-Barré syndrome and antecedent C jejuni infection.5 The antecedent infectious symptom was diarrhoea in three of five patients with axonal Guillain-Barré syndrome described by Feasby et al.3 Observations by Griffin et al 4 confirmed that AMSAN followsC jejuni infection. Serum samples from patients with axonal Guillain-Barré syndrome subsequent toC jejuni enteritis often have IgG class autoantibodies to gangliosides GM1, GM1b, GD1a, or GalNAc-GD1a in the acute phase of the illness,6 and there is molecular mimicry between these gangliosides and the lipopolysaccharides of C jejuni isolates from patients with Guillain-Barré syndrome.6 This ganglioside mimicry may trigger high production of the IgG antiganglioside antibodies, and these autoantibodies may cause motor nerve dysfunction in patients with GBS.
Interestingly, Hagensee et al 7reported a case of “C jejuni bacteremia and subsequent Guillain-Barré syndrome”that occurred in a patient with chronic graft versus host disease after allogenic bone marrow transplantation. Because there was acute flaccid paralysis associated with sepsis, some physicians might have diagnosed critical illness polyneuropathy. Conversely, the existence of this case strongly suggests that some diagnoses of critical illness polyneuropathy should actually be axonal Guillain-Barré syndrome or AMSAN. Our hypothesis of the nosological relation between critical illness polyneuropathy and axonal Guillain-Barré syndrome is shown in the figure. Serum IgG antibodies against GM1, GM1b, GD1a, or GalNAc-GD1a could be used as immunological markers for axonal Guillain-Barré syndrome.6 To examine the aetiology of critical illness polyneuropathy and its nosological relation to axonal Guillain-Barré syndrome, it is necessary to investigate whether patients with critical illness polyneuropathy have antiganglioside antibodies during the acute phase of the illness.
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