Diagnosis of peripheral neuropathy

Abstract

Introduction: Peripheral neuropathy represents a spectrum of diseases with different etiologies. The most common causes are diabetes, exposure to toxic substances including alcohol and chemotherapeutics, immune-mediated conditions, and gene mutations. A thorough workup including clinical history and examination, nerve conduction studies, and comprehensive laboratory tests is warranted to identify treatable causes.

First steps: The variability of symptoms allows distinguishing characteristic clinical phenotypes of peripheral neuropathy that should be recognized in order to stratify the diagnostic workup accordingly. Nerve conduction studies are essential to determine the phenotype (axonal versus demyelinating) and severity. Laboratory tests, including genetic testing, CSF examination, nerve imaging, and nerve biopsy, represent additional clinical tests that can be useful in specific clinical scenarios.

Comments: We propose a flow chart based on five common basic clinical patterns of peripheral neuropathy. Based on these five clinical phenotypes, we suggest differential diagnostic pathways in order to establish the underlying cause.

Conclusions: The recognition of characteristic clinical phenotypes combined with nerve conduction studies allows pursuing subsequent diagnostic pathways that incorporate nerve conduction studies and additional diagnostic tests. This two-tiered approach promises higher yield and better cost-effectiveness in the diagnostic workup in patients with peripheral neuropathy.

Keywords: CIDP; Diabetic; Diagnosis; EMG; Hereditary amyloid transthyretin (ATTRv) amyloidosis; Nerve conduction studies; Peripheral neuropathy; Ultrasound.

Fig. 1

Flow chart of a diagnostic algorithm for the workup of patients with peripheral neuropathy. According to the established clinical patterns, based on clinical history and examination, diagnostic procedures can be stratified. Abs = antibodies, ATTRv = hereditary transthyretin amyloidosis, CIAP = chronic idiopathic axonal polyneuropathy, CSF = cerebrospinal fluid, i.a.= if applicable, SNAP = sensory nerve action potential

Fig. 2

a Disease onset and temporal evolution characteristics of distinguishable clinical patterns and different causes of peripheral neuropathy. b Clinical patterns of polyneuropathy: Sensory deficits are drawn in blue, motor deficits are drawn in red, and sensorimotor in magenta color. Painful and / or autonomous dysfunction is colored with green lines. Loss of proprioception is colored in brown. Pattern #1 is a distal symmetric predominantly sensory neuropathy, #2 a motor neuropathy with muscle wasting and foot abnormalities; pattern #3 is characterized by proximal involvement of sensory and motor nerve fibers, pattern #4 presents wih multifocal symptoms, neuropathic pain, and autonomic dysfunction. Pattern #5: is a sensory ataxic neuropathy