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The Guillain-Barré Syndrome (GBS) is the most common cause of acute neuromuscular paralysis in developed countries, affecting 1–2 people per 100,000 annually. The mortality is about 10%, and approximately 20% of patients are left with significant motor disability. Our understanding of GBS has evolved since Landry’s description of the clinical features of “acute ascending paralysis” in the late 1800s and Guillain and Barré’s recognition of the albuminocytological dissociation in the cerebrospinal fluid in the early 1900s. It is classically regarded an acute demyelinating polyradiculoneuropathy, characterized clinically by the acute onset of symmetric weakness and arreflexia with relatively minor sensory impairment. Cerebrospinal fluid (CSF) analysis characteristically yields an elevated protein concentration but little or no pleocytosis, and the electrophysiology reveals evidence of demyelination. Over the years, however, unusual variants of this syndrome have been recognized, including an axonal form. Plasmapheresis and intravenous immunoglobulin (IVIg) have become the mainstay of therapy and steroids are thought not to be beneficial.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired demyelinating neuropathy in which motor symptoms generally predominate over sensory symptoms and large fiber sensory dysfunction is more common than small fiber loss. The course may either be relapsing and remitting or chronically progressive. CIDP may occur in isolation or in the context of a number of systemic disorders, including HIV and hepatitis C infection, inflammatory bowel disease, lymphoproliferative disorders and osteosclerotic myeloma. The importance of distinguishing CIDP from among other causes of peripheral neuropathy lies in the observation that a significant proportion of patients with CIDP may respond to immune-modifying therapy. In this chapter, we consider important diagnostic questions that relate to the optimal electrophysiological criteria that should be used to define the disorder and the relative diagnostic utility of sural nerve biopsy. Many different forms of immunosuppressive therapy have been proposed for the treatment of CIDP, and although some of these therapeutic modalities have been studied in randomized controlled trials, many have not. We shall also consider the evidence supporting the use of these various immunosuppressive agents as well as the prognosis for patients who are treated in this manner.

Multifocal motor neuropathy (MMN) is a relatively recently recognized clinical entity that was formally described by Parry and Clark in the mid-1980s (,). The clinical presentation in each of the patients in this original series had suggested a diagnosis of motor neuron disease, but nerve conduction studies showed multifocal conduction block in motor nerves. The recognition that this syndrome represented a form of a chronic demyelinating neuropathy has spawned much debate regarding its relationship to other chronic demyelinating neuropathies such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and the Lewis-Sumner syndrome, and has also raised the possibility that patients with the disorder might respond to immunosuppressive therapy. What are the clinical and electrophysiological features of MMN, and how does it differ from other chronic demyelinating neuropathies? What is the diagnostic accuracy of anti GM1 antibodies? Do patients with MMN respond to immunosuppressive therapy, and what is the long term prognosis for patients with this disorder? These and other questions are the focus of this chapter.

The inherited neuropathy literature is complex, in part because of the incomplete correlation between genotype and phenotype and in part because of the confusing array of terminology that has been used to describe and classify these disorders. The terms “hereditary motor and sensory neuropathy” (HMSN) and “Charcot-Marie Tooth” (CMT) have both been used to describe the same group of disorders. HMSN-I and HMSN-II are synonymous with CMT-1 and CMT-2 respectively, with the distinction between CMT 1 (HMSN-1) and CMT-2 (HMSN-2) being based on the electrophysiological finding of marked slowing of motor conduction velocities in the former. Recent advances in molecular genetics have shown that mutations in several different genes may underlie the various inherited neuropathies. The expanding array of genetic mutations has further complicated the classification of this group of disorders. The current approach rests on the mode of inheritance and electrophysiological features of the disorder. A simplified classification is presented in Table 14.1. Most of the inherited neuropathy literature has focused on diagnostic issues, with relatively little attention paid to treatment and prognosis. This bias is reflected in this chapter, in which we examine the clinical and electrophysiological features of the hereditary neuropathies and ask whether the various disorders can be differentiated on clinical or electrical grounds. We also consider the electrophysiological differences between acquired and hereditary neuropathies of both the demyelinating and axonal types. Finally, we do consider several treatment and prognosis related issues.

Carpal tunnel syndrome (CTS) is a clinical disorder caused by compression of the median nerve at the wrist. The diagnosis can be made with confidence in patients with the typical clinical and electrodiagnostic features. It is the most common entrapment neuropathy with a cumulative lifetime incidence of approximately 8%. As a common cause of pain and functional impairment of the hand, it represents a significant cause of morbidity in the general population.

Ulnar neuropathy at the elbow (UNE) is the second most commonly encountered entrapment neuropathy after carpal tunnel syndrome. The term “cubital tunnel” syndrome is sometimes used to refer to UNE, but this is misleading as the term accurately describes only compression of the ulnar nerve as it passes beneath the aponeurotic arch of the flexor carpi ulnaris muscle (FCU). Because the ulnar nerve may also be compressed in the ulnar (condylar or retrocondylar) groove behind the medial epicondyle, the term UNE is more encompassing of the range of pathophysiological processes that may lead to ulnar nerve injury in the vicinity of the elbow. Compressive lesions of the ulnar nerve as it passes across the elbow may selectively affect some nerve fascicles more than others, which may cause some difficulty in localizing an ulnar nerve lesion to the elbow. What then are the typical clinical features of ulnar neuropathy at the elbow and how accurate are the various electrophysiologic tests for the diagnosis of UNE? What is the natural history of UNE if left untreated and how do conservative and surgical measures impact this prognosis? These and other questions are the subject of this chapter.

Myasthenia gravis (MG) is an autoimmune disorder in which antibodies are either directed against the muscle nicotinic acetylcholine receptor (nAChR) itself or against other postsynaptic targets such as the muscle specific kinase (MuSK) that indirectly reduce nAchR numbers. The disease may be limited to the extra-ocular muscles and eyelids (ocular myasthenia) or may affect limb, bulbar and respiratory muscles (generalized myasthenia). The relative diagnostic utility of electrophysiological tests and the presence of anti-acetylcholine receptor antibodies vary depending on whether the disease is ocular or generalized. MG is the prototype neurological auto-immune disorder in which both antigen and antibody have been identified, removal of antibody has been shown to lead to clinical improvement, and the disease can be recreated in mice following passive transfer of the auto-antibody. Understandably, therefore, immunosuppressive therapy forms the mainstay of disease-modifying treatment, with acetylcholinesterase inhibitors being reserved for symptomatic management.

The Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune presynaptic disorder of neuromuscular transmission in which antibodies are directed against the voltage-gated calcium channel. The classic clinical features include proximal muscle weakness, depressed deep tendon reflexes, and prominent symptoms of autonomic dysfunction. The hallmark electrophysiological finding is a reduction in the size of the compound muscle action potential with facilitation (i.e., increased in amplitude) following brief sustained muscle contraction. In many patients, LEMS may occur in association with an underlying malignancy as a paraneoplastic disorder. How frequently are these clinical and electrophysiological features encountered in patients with LEMS? How specific is the finding of compound muscle action potential facilitation for the diagnosis? Is the presence of antibodies against voltage-gated calcium channels specific for LEMS? Should patients with LEMS be treated with immunosuppressive therapy notwithstanding the frequency with which underlying malignancies are detected? What is the long-term prognosis of LEMS, and does the presence of LEMS affect the prognosis for patients with small cell lung carcinoma? These and other questions are the subject of this chapter.

The idiopathic inflammatory myopathies include polymyositis (PM), dermatomyositis (DM), and sporadic inclusion body myositis (s-IBM). Although the clinical presentation of PM and DM may be very similar apart from the presence of a skin rash in the latter, it is important to note that DM is not simply “PM with a rash.” Similarly, although there are histolopathological similarities between PM and s-IBM at the light-microscopic level, inclusion body myositis is not merely “PM that is unresponsive to steroids.” PM, DM, and s-IBM are, in fact, three immunopathologically distinct entities. In PM, the immune attack is directed primarily at the muscle fiber. There is increased major histocompatibility (MHC)-I antigen expression on muscle fibers and there is cytotoxic (CD) T-cell mediated destruction of otherwise healthy muscle fibers. In DM, by contrast, the immune-attack is primarily directed against intra-muscular blood vessels, i.e., it is a microvascular angiopathy with muscle fiber destruction being a secondary phenomenon. The pathophysiology of s-IBM is less clear. Although it is typically characterized by an endomysial cytotoxic T-cell inflammatory infilatrate, as seen in PM, it is unclear whether the inflammatory infiltrate is the primary event. The presence of vacuoles containing a variety of proteins including amyloid and ubiquitin suggests a primary degenerative disorder of muscle.

Idiopathic hyper-CK-emia is a term used to describe the finding of an elevated serum creatine kinase (CK) concentration in the absence of symptoms (or only minimal symptoms) that can be attributed to an underlying neuromuscular disease. The discovery of a high serum CK, even when asymptomatic or pauci-symptomatic, raises the prospect of an underlying neuromuscular disorder and typically prompts referral for further evaluation. The next diagnostic steps are likely to involve electromyography (EMG) and muscle biopsy. Questions arise, however, regarding the diagnostic yield of these investigations and the frequency with which a definitive diagnosis can be made and, more importantly, the frequency with which a disorder which warrants (and is likely to respond to) therapy can be identified. This chapter focuses on the diagnostic yield of EMG and muscle biopsy and the relationship between idiopathic hyper-CK-emia and the risk of malignant hyperthermia.