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Epidemiology is a discipline that studies the distribution and determinants of disease. The applications of epidemiology are diverse and include identifying causal mechanisms of disease, diagnostic testing, determining prognosis, and testing new treatments. The goal of an epidemiological study is valid measurement. To understand this goal, it is necessary to understand what it is that is being measured and what is meant by the term validity. The epidemiologist is usually interested in measuring the relationship or association between some exposure and some outcome. The first step is to measure the frequency of the exposure and/or the frequency of the outcome (e.g., disease) of interest. It is then possible to compare these measures of frequency between two populations. The demonstration that disease occurs more frequently within a population exposed to some risk factor than within a population without such exposure provides insight into the association between the exposure and the disease. “Validity” describes the extent to which a measurement is correct (i.e., reflects the truth). A major difficulty is that we typically do not know the truth. Ensuring validity, therefore, requires that we take precautions to minimize error. Broadly speaking, epidemiological studies are susceptible to two types or error—systematic error (also known as bias) and random error. Error is reduced by an awareness of its origins and by the use of appropriate study design.

The clinical decision-making process is based on probability. Based on certain clinical information such as risk factors, family history, and findings on physical examination, the clinician obtains some estimate of the probability of disease (the pretest probability). Diagnostic tests are performed in order to improve the estimate of this probability. If the test is negative, the probability of disease should fall and if the test is positive, then the probability of the disease should rise. Useful diagnostic tests will produce marked shifts in the probability of disease based on whether the results of the test are positive or negative.

The randomized controlled trial (RCT) is a powerful experimental technique for demonstrating the efficacy of a therapeutic strategy. The goal of the RCT is to obtain a valid measure of the efficacy of a particular intervention. Validity is maximized by strict adherence to the design elements of the RCT that aim to minimize bias, confounding, and random error.

Determining the prognosis of a disease involves a prediction of the probable outcome. The term natural history is sometimes used synonymously with prognosis, but it is probably better used to describe a particular sort of prognosis—that which ensues in the absence of any therapeutic intervention. The most reliable information about the outcome of a disease is usually derived from the experience of other patients with the same disorder. To estimate prognosis, therefore, we typically examine the outcome of a group of patients who all have the same disorder. To refine our estimate of the prognosis, we compare outcome among subgroups of patients based, for example, on age, gender, comorbidity, or some other variable. Variables or factors that really do predict outcome are known as . Prognostic factors are really just examples of risk factors. In the same way that risk factors predict the occurrence of disease, prognostic factors predict the outcome of disease.

Amyotrophic lateral sclerosis (ALS) is a degenerative disorder characterized by loss of motor neurons in the spinal cord, brainstem, and cerebral cortex. It is an uncommon disease with an incidence in the range of 1–2.5 cases per 100,000 population. Incidence increases with age and there is a slight male preponderance. The etiology is unknown, and the progression of the disease is almost uniformly relentless, resulting in death.

Cervical spondylosis is a disorder characterized by degenerative disc disease, the formation of spondylotic ridges and osteophytes, facet and uncovertebral joint arthritis, ossification of the posterior longitudinal ligament, redundancy of the ligamentum flavum, and vertebral body listhesis. Injury to nerve roots or the spinal cord may occur either directly via mechanical trauma or compression, or indirectly via arterial insufficiency or venous stasis.

In considering an approach toward the diagnosis, management, and prognosis of lumbar spine disease, a distinction can be made between acute lumbar disc herniation (“soft” disease) and degenerative lumbar spondylosis (“hard” or “bony” disease). The spectrum of the clinical manifestations of lumbar spine disease is broad, and includes back pain, with radiation into the leg (sciatica), lumbar radiculopathy (signs and symptoms of nerve irritation and/or radicular neurological deficit), and neurogenic intermittent claudication (pain and/or weakness that increases with walking and subsides with rest). The term spinal stenosis refers to any narrowing of the spinal canal, the nerve root canals, or the intervertebral foramina. Central (or canal) stenosis leads to impingement on the dura and cauda equina, whereas lateral (foraminal or lateral recess) stenosis results in compression of the nerve roots. Although there is no clear correlation between the nature of the underlying disease (i.e., soft vs hard disease) and the clinical symptomatology, it is useful to recognize these distinctions for the purposes of understanding the pathophysiology of lumbar spine disease because, at least in theory, different therapeutic approaches may be appropriate.

Peripheral neuropathies may be characterized as being focal, multifocal (asymmetric), or diffuse (symmetric). Polyneuropathy is the term used to describe a diffuse (symmetric) disorder of peripheral nerves. Polyneuropathy is typically considered a length-dependent or dying-back neuropathy in which symptoms begin in the feet and evolve symmetrically to affect more proximal aspects of the legs and eventually the hands as well. Most polyneuropathies affect sensory fibers earlier and more prominently than motor fibers, but this is certainly not uniformly so. Polyneuropathy is a disorder that is easily recognized by a neurologist when symptoms are accompanied by typical physical findings on examination (reduced or absent distal deep tendon reflexes, distal “stocking” pattern sensory loss, and/or distal muscle weakness and atrophy). Nerve conduction studies play an important role in defining the presence of a polyneuropathy and in terms of delineating the underlying pathophysiological process (i.e., primary axonal loss vs primary demyelination). Because nerve conduction studies only measure the activity of large fiber nerves, skin biopsy to determine the density of epidermal nerve fibers has been suggested as a useful test for the diagnosis of polyneuropathies that predominantly (or exclusively) affect small fiber nerve populations. Clinical examination and nerve conduction studies, however, will seldom facilitate an etiological diagnosis. Laboratory studies and nerve biopsy are the tests most commonly employed used to determine the cause of the polyneuropathy.

The detection of a monoclonal protein (gammopathy) in the serum of a patient with a peripheral neuropathy is important for two reasons. First, it may provide information about the prognosis and likelihood of response to immunosuppressive therapy. Second, it may indicate the presence of an underlying plasma cell proliferative disorder, such as multiple myeloma, osteosclerotic myeloma, Waldenstrom’s macroglobulinemia, or primary systemic amyloidosis. The term monoclonal gammopathy of undetermined significance (MGUS) has been used when no specific hematological diagnosis is forthcoming.

The term “vasculitis” is used to describe a group of disorders that are characterized by the presence of a specific pathological finding—namely, inflammation and necrosis of blood vessel walls. Broadly speaking, this group of disorders may be classified into the systemic and nonsystemic (or localized) vasculitides. The systemic vasculitides encompass a broad range of diseases including (a) the vasculitides that result from direct infection of the blood vessel wall (e.g., syphilis, tuberculosis, and HIV infection), (b) the necrotizing vasculitides (e.g., polyarteritis nodosa, Churg-Strauss syndrome, Wegener’s granulomatosis, and the connective tissue disorders rheumatoid arthritis, systemic lupus erythematosis, and Sjogren’s syndrome), (c) the hypersensitivity vasculitides (e.g., druginduced cryoglobulinemia and malignancy) and (d) the giant cell arteritides (temporal arteritis and Takayasu’s arteritis). The nonsystemic vasculitides may affect either the central or the peripheral nervous system exclusively. In this chapter, we are concerned with the form of nonsystemic vasculitis that is confined to the peripheral nervous system as well as the systemic vasculitides in which the peripheral nervous system is also affected.