Chapter 31 - Diseases of the peripheral nerves

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Abstract

This chapter reviews the diseases of the peripheral nerves from a neuropathologic point of view, with a special focus on specific morphologic changes, and includes a summary of the histopathologic methods available for their diagnosis. As the rate of obesity and the prevalence of type 2 diabetes increase, diabetic neuropathy is the most common cause of peripheral neuropathy. Many systemic disorders with metabolic origin, like amyloidosis, hepatic failure, vitamin deficiencies, uremia, lipid metabolism disorders, and others, can also cause axonal or myelin alterations in the peripheral nervous system. The most notable causes of toxic neuropathies are chemotherapeutic agents, alcohol consumption, and exposure to heavy metals and other environmental or biologic toxins. Inflammatory neuropathies cover infectious neuropathies (Lyme disease, human immunodeficiency virus, leprosy, hepatitis) and neuropathies of autoimmune origin (sarcoidosis, Guillain–Barré syndrome/acute inflammatory demyelinating polyneuropathy, chronic inflammatory demyelinating polyneuropathy, and diverse forms of vasculitis. The increasing number of known diseases causing gene mutations in hereditary peripheral neuropathies requires precise characterization, which includes histopathology.

Introduction

Due to its long-reaching and complex structure, the peripheral nervous system (PNS) is exposed to many environmental, metabolic, and genetic predispositions and affected by a myriad of diseases. From a neuropathologist's point of view, the main criteria of their classification are structural and based on which components of the peripheral nerves are affected. From this aspect they can be axonal, demyelinating, or mixed; this categorization, of course, should be further refined on the basis of clinical and electrophysiologic features and by genetics. A characteristic neuropathologic finding can often be the decisive factor in the diagnostic process or during the therapeutic course.

Here we give a general overview of the diseases of the peripheral nerves (Table 31.1), taking a neuropathologic approach, providing a rundown of important structural pathologies, as well as a summary of histopathologic methods available for their diagnosis.

Section snippets

Nerve biopsy

Nerve biopsy is undoubtedly a singular tool for detecting pathologic changes of the PNS and for the diagnosis of peripheral neuropathies. Even with the ever more accessible methods of genetic testing it is a useful complement to solve etiologic questions by revealing histopathologic and ultrastructural patterns specific to certain subtypes of hereditary neuropathies, or even to a particular gene defect, hence advancing and guiding the genetic diagnostic process. One of the primary indications

Common pathologic alterations of the peripheral nerve

The PNS is made up of several major components. The peripheral motor, sensory, and autonomic neurons, their afferent and efferent axons, myelinating and nonmyelinating Schwann cells and, last but not least, the connective tissue components (endoneurium, perineurium, epineurium, blood and lymphatic vessels) can all be differentially involved, either primarily or as a secondary effect. The axonal component of the lesion is predominant in the majority of the cases, followed by the demyelinating

Hereditary neuropathies

We have witnessed a proliferation of known genes and mutations causing monogenic hereditary neuropathies in recent years (Rossor et al., 2013). There are more than 100 disorders categorized in this group with a very wide range of mutated gene functions, from “classic” myelin proteins to ubiquitously expressed transcription factors, and a similarly wide scale of clinical manifestation. Diseases belonging to this group can be sorted into four major subgroups based on their predominant phenotype,

Diabetic neuropathy

With the steeply rising prevalence of diabetes, diabetic neuropathy has become the most frequent form of peripheral neuropathy. In an earlier study 66% of patients with type 1 diabetes and 59% of patients with type 2 diabetes developed some form of neuropathy (Dyck et al., 1993). Currently, the prevalence of neuropathy in adult diabetic patients is estimated at 50% (Juster-Switlyk and Smith, 2016). A considerable number of different forms of diabetic neuropathy are distinguished based on the

Introductory remarks

The inflammatory neuropathies include autoimmune neuritis as well as neuritis directly related to infection of the nerve. Autoimmune neuritis may be triggered by previous bacterial infections such as enteritis. Paraneoplastic neuropathy is caused by an immune reaction against tumor antigens that leads to an autoimmune response against nerve fibers and/or neuronal cell bodies. Vasculitic neuropathy may be due to inflammation selectively affecting the blood vessels of the nerve, or to systemic

Conclusions

The PNS extends to the entire human body, providing an accessible and important window to investigate our nervous system. Alongside clinical and genetic testing, histopathologic evaluation of material from patients with disorders of the peripheral nerves – primarily sural nerve biopsy, and increasingly, skin biopsy – is a powerful tool for the diagnosis of neuropathies, giving invaluable clues to clinicians and geneticists for diagnosis and therapy.

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