Small Fiber Neuropathy in Critical Illness
By Russell L. Chin, MD
Associate Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Chin reports no financial relationships relevant to this field of study.
SYNOPSIS: The spectrum of critical illness polyneuropathy may include painful, small-fiber degeneration that can be readily diagnosed by punch skin-biopsy.
SOURCE: Skorna M, et al. Small-nerve-fiber pathology in critical illness documented by serial skin biopsies. Muscle Nerve 2015;52:28-33.
Chronic pain and sensory impairment often occur as a consequence of critical illness, and these symptoms have been viewed as part of the spectrum of critical illness polyneuropathy (CIP). To investigate the mechanism of this disorder, the investigators performed skin biopsies upon admission to the critical care unit and 10-14 days later to follow the course of any neuropathic disease.
Skin biopsies from one leg were obtained to measure intraepidermal nerve fiber density (IENFD) in 11 patients admitted to the neurocritical care unit for ischemic stroke. Nine of the patients developed sepsis or multi-organ failure during this period. Repeat skin biopsies from the opposite leg were obtained 10-14 days later. The median IENFD on admission (5.05 fibers/mm) decreased significantly to 2.18 fibers/mm (P < 0.001). Six patients had abnormal IENFD on final skin biopsy (two of them were already abnormal on admission). Electrodiagnostic signs of large fiber neuropathy and/or myopathy were found in six patients (54.5%) and autonomic dysfunction was found in two patients (18.2%).
Critical illness myopathy (CIM), CIP, and a combination of both (critical illness polyneuromyopathy) are well-recognized disorders that can develop in the setting of prolonged ventilation and neuromuscular blockade, with glucocorticoid exposure and the development of sepsis, systemic inflammatory response syndrome, or multi-organ failure. CIM (also called thick filament myopathy) may be difficult to distinguish from CIP due to the technical difficulties encountered in performing detailed electrodiagnostic studies in the ICU. Limb edema may prevent the detection of sensory responses and assessment of motor unit morphology, which is essential to the diagnosis of myopathy, may be limited by poor patient cooperation in the setting of encephalopathy. The presence of a pre-existing neuropathy may also cloud the assessment.P
Some data suggest that most patients with acquired neuromuscular disease due to sepsis have the combination of CIM and CIP and that an early drop in nerve conduction responses portends a higher mortality. Complete functional recovery (with the ability to breathe spontaneously and walk independently), however, has been reported in a majority (68% ) of patients, while 28% experience chronic, severe disability. Milder residual symptoms, including hypo- and hyperesthesias, reduced or absent deep tendon reflexes, and foot drop, may be present in all patients.2
The pathogenesis of axonal injury in CIP is poorly understood. Injury to the microcirculation of distal nerves, causing ischemia and axonal degeneration, has been suggested. Dorsal root ganglia neurons are surrounded by fenestrated capillaries and may be exposed to neurotoxins released during sepsis or systemic inflammatory response syndrome.3
Skin punch biopsy is a simple, minimally invasive technique to evaluate for small fiber neuropathy, which is characterized by degeneration and loss of IENFD. It is useful in the setting of sensory symptoms without evidence of large fiber dysfunction.2
This study provides useful information about the chronology of critical illness neuromuscular disease in the acute stage. All of the included patients had unremarkable electrodiagnostic studies on admission, but six patients (54.5%) developed neuropathy and/or myopathy at the time of repeat testing 10-14 days later. The proportion of patients with abnormal IENFD also increased in this time frame (from two patients on admission to six patients after repeat skin biopsy).
Involvement of the small nerve fibers appears common in isolation or with large fiber neuropathy or myopathy and could be predictive of symptomatic, painful small-fiber neuropathy.
- Latronico N, et al. Neuromuscular sequelae of critical illness. Curr Opin Crit Care 2005;11:381-390.
- Latronico N, et al. Small nerve fiber pathology in critical illness. PloS One 2013;8:e75696.
- Khan J, et al. Early development of critical illness myopathy and neuropathy in patients with severe sepsis. Neurology 2006;67:1421-1425.
The spectrum of critical illness polyneuropathy may include painful, small-fiber degeneration that can be readily diagnosed by punch skin-biopsy.
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