Pathophysiology of very early classic Guillain-Barré syndrome: a heterodox approach

Abstract

The aim of this paper is to analyze the pathophysiological mechanisms acting in very early classic Guillain-Barré syndrome (GBS) (≤ 4 days of symptomatic onset; GBS). In this inaugural period, both in GBS and its animal model, experimental autoimmune neuritis, the outstanding pathological feature is inflammatory edema predominating in proximal nerve trunks, particularly spinal nerves, and possibly in pre-terminal nerve segments. Nerve trunks external to the subarachnoid angle possess epi-perineurium that is relatively inelastic and of low compliance. Here, such edema can increase endoneurial fluid pressure that, when critical enough, may stretch the perineurium and constrict transperineurial microcirculation compromising blood flow and producing the potential for ischemic nerve injury, whose consequence is rapid partial or complete loss of nerve excitability. These histopathological features correlate well with electrophysiological and imaging findings reported in early GBS stages. Spinal nerve edema and ischemia help to understand the pattern of Wallerian-like degeneration observed in the axonal form of GBS, predominating in motor spinal roots at their exit from the dura matter (spinal nerves) with centrifugal distribution in more distant motor nerve trunks, and centripetal extension to the distal portion of intrathecal roots. The similarity of initial pathogenic mechanisms between demyelinating and axonal forms of GBS explains why an early increase of serum biomarkers of axonal damage is detected in both forms. In conclusion, knowledge of microscopic anatomy of the peripheral nervous system and initial clinical-pathological events, although it may seem a heterodox approach, are fundamental to understanding the nosology of established GBS.