Peripheral Neuropathies

This issue of Seminars in Neurology is devoted to peripheral neuropathies. The subject of peripheral neuropathies is large and a single issue cannot cover the full spectrum. The articles selected for this issue are based on common problems and clinical issues encountered in practice. Articles include an approach to the clinical evaluation; an approach to electrodiagnosis with commentary on technical and interpretative errors; clinical and diagnostic features of inflammatory, bariatric, hereditary, and unusual neuropathies; and a review of diagnostic testsas well as treatment of inflammatory neuropathies and neuropathic pain. Several topics are not included, such as diabetic neuropathy (because features are well described in the literature) and nerve biopsies (because they are seldom performed and are rarely diagnostic).

It is worthwhile to briefly discuss the spectrum of peripheral neuropathies as the term “peripheral neuropathy” is very broad. The anatomic entity of axons wrapped by peripheral myelin is simple in concept but histologically and metabolically complex, and hence subjected to a wide variety of disturbances. The boundaries of the peripheral nervous system cannot be precisely defined to include all disorders clinically considered to be “peripheral neuropathies.” Histologically, the peripheral nervous system can be considered to be the neurons ensheathed by Schwann cells, and this would include cranial nerves and spinal nerves. There are difficulties in classifying some types of peripheral neuropathies. Disorders that damage peripheral processes of motor nerves are easily categorized as peripheral neuropathies, whereas disorders that affect anterior horn cells (neuronopathies) are generally categorized as motor neuron diseases even though there may be a significant component of a dying-back process in the peripheral system. Many disorders of sensory nerves, especially those affecting cell bodies in the dorsal root ganglia, will also include involvement of the branch extending into the central nervous system. Some disorders may be predominantly peripheral but include pathology of both central and peripheral axons or myelin. Some immune-mediated neuropathies may include functional alteration of conduction and not structural damage to myelin or axons. Painful neuropathies may affect only intraepidermal nerves.

Peripheral neuropathies can be categorized by different schemas (Table [1]). There will be overlap or combinations among the schemas for a given clinical entity.

Table 1 Classification of Peripheral Neuropathies Based on Different Schemas By anatomic distribution Mononeuropathy, mononeuropathy multiplex, diffuse-polyneuropathy, symmetric, asymmetric, distal, distal and proximal, cranial, peripheral and central, intraepidermal By modality Sensory, motor, autonomic By time course Acute (weeks), chronic, relapsing–remitting, insidious By symptoms Pain, sensory loss, weakness, dystaxic By basic pathology Primary axonal, primary demyelination, primary conduction block (mechanical, demyelinating, functional) By basic disease process Acquired, hereditary, compressive, traumatic By pathophysiology Metabolic, toxic, hereditary, immune-mediated, to cell body, to axon, to myelin, ischemic, mechanical, idiopathic By association with Systemic diseases, cancer (direct, paraneoplastic), infections By test features Subclinical, primary axonal, primary demyelination, primary conduction block, nerve or skin biopsy, associated laboratory findings

Many neuropathies will be characterized by one or more features from several of the above categories. Despite complexity, the evaluation process described in this issue of Seminars in Neurology argues for an orderly approach. Table 1 becomes simplified as the neuropathy is fully characterized, first by the history and examination, and second by the electrodiagnostic testing. At that point informative laboratory testing can be ordered. It is hoped that this issue will help organize the evaluation process.