Chapter 19 Disorders of the Nervous System

The nervous system is a complex and intricate system that enables the individual to recognize and react to the environment and to interact with the environment in a meaningful manner. Underlying this complex system is its simplicity of composition, with relatively few distinct cell types including neurons and glial cells. The nervous system is organized into the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS receives, processes, and initiates signals, whereas the PNS relays signals to and from the environment and the CNS. In both systems, the neuron is the principal cell type. Neurons communicate with their targets via long cytoplasmic processes called axons. In the PNS, the peripheral nerves are primarily composed of bundles of axons and their associated Schwann cells. Schwann cells provide protection and trophic support and are found in two phenotypes—myelinating and nonmyelinating. Myelinating Schwann cells ensheathe large-caliber axons in myelin and maintain a one-to-one relationship with axons. Myelination increases the speed of action potential propagation and allows signals to reach their targets in a timely manner. In contrast, nonmyelinating Schwann cells associate with numerous axons in structures known as Remak bundles, which enclose small caliber C fibers and transmit pain and temperature sensation. The loss of myelination and changes in Remak bundles are common signs of peripheral nerve neuropathy. This chapter will describe the structure and function of the human nervous system and discuss the pathophysiology of specific neuropathies that are important in orthopaedic clinical practice. Peripheral nerves are heterogeneous composite structures composed of neurons, Schwann cells, fibroblasts, and macrophages. The neuron is a polarized cell that forms the foundation of the nerve and consists of dendrites, the cell body, and a single axon. The cell body contains the nucleus, cytoplasmic organelles, and a cytoskeleton composed of neurofilaments and microtubules. The axon originates from a unique region of the cell body called the axon hillock, which is the site where the action potential of the neuron is produced. Axons project toward sites of innervation, where they form synapses. Synaptic transmissions from the axon to the end organ are mediated by electrochemical changes. In the PNS, the axons are surrounded by glial cells called Schwann cells, which produce myelin. If the axonal diameter is greater than or equal to 1 μm, each Schwann cell will wrap its plasma membrane around a single region of an axon and develop myelin. This myelin, composed of 70% lipid and 30% protein, functions to provide fast and efficient conduction of the action potential propagating down an axon. Discontinuities along the length of the axon in the myelin sheath are called the nodes of Ranvier. When the action potential reaches a node, it depolarizes sodium channels. This rapid action potential propagation down the axon from node to node occurs by a process called saltatory conduction. Peripheral nerves have connective tissue layers to provide strength and protection to the nerve with its three layers: the endoneurium, perineurium, and epineurium (Figure 1). The endoneurium surrounds individual axons and their associated Schwann cells. It is composed of thin collagen strands that provide nourishment and protection. Multiple nerve fibers form a collection of axons called a fascicle. Fascicles are grouped and surrounded by the perineurium, which is composed of collagen and fibroblasts. This sheath provides the nerve with tensile strength, and the fibroblasts contribute to the formation of the blood-nerve barrier. Multiple fascicles are grouped together and surrounded by a connective tissue layer called the internal or interfascicular epineurium. This layer cushions the fascicles within the nerve and allows them to move freely against one another. The periphery of the entire nerve is covered by the external or extrafascicular epineurium, which protects the entire nerve from the surrounding environment. The CNS consists of functions served both in the brain and in the spinal cord. The brain is structurally organized into lobes (the gray matter) named the fronDr. Mozaffar or an immediate family member is a member of a speakers’ bureau or has made paid presentations on behalf of Genzyme Talecris; serves as a paid consultant to or is an employee of Genzyme, Baxter, and Talcris; has received research or institutional support from Talecris Biotherapeutics; and has received nonincome support (such as equipment or services), commercially derived honoraria, or other non-research–related funding (such as paid travel) from the medical director for Crescent Healthcare. Dr. Gupta or an immediate family member has received funding from the NIH-NINDS and has received research or institutional support from Arthrex, Smith & Nephew, and Synthes.