Although the blood-brain barrier protects the nervous system from microorganisms, it may be damaged by bacteria, viruses, fungi, and other organisms. If damage occurs, resistance to infection of the nervous system is decreased. The major classes of inflammatory disease are meningitis and encephalitis (infections of the meninges, or covering membranes, of the brain and of the brain itself, respectively) and abscesses, which may be situated outside or just below the meninges or in the brain itself. Some viruses lie almost dormant within neural tissue for years before causing destruction. The measles virus may do this, causing a chronic progressive encephalitis that is usually fatal.
Direct infections of muscles and of peripheral nerves are uncommon except in leprosy. Both the central and peripheral nervous systems may be severely damaged by an immune system reaction after relatively trivial infections elsewhere in the body. Finally, in some infections such as diphtheria and botulism, a toxin liberated by the infectious organism attacks the nervous system.
Trauma
Traumatic and mechanical injuries can affect all levels of the nervous system. Serious head injuries can lead to compression, laceration, or bruising of the brain inside the cranium. Compression is commonly due to a blood clot inside the brain or formed outside or beneath the dura mater (extra- or subdural hematoma), but inherent swelling of the brain tissue following trauma is also possible as fluid leaks from small blood vessel spaces into the extravascular space (brain edema). Later consequences, such as seizures and alterations in mental processes and personality, indicate damage done to the brain by major or repeated minor head injuries. Less serious head injuries may cause a concussion, a temporary loss of awareness.
Once destroyed, neurons are not replaced. Severed axons sprout growths from the cut end, but they do not form effective connections in the brain or spinal cord. Therefore, destructive injury of, for example, the spinal cord is followed by permanent loss of voluntary movement and of sensation below the level of injury.
In the peripheral nervous system, axons that have been severed or have degenerated because of disease can grow again. If the nerve remains in continuity, sprouting axons may eventually reestablish effective connections with muscle fibres or sensory organs, but reinnervation is often abnormal because of division and misdirection of growing axons.
Neoplasms
Both benign and primary and secondary malignant tumours can attack the meninges, the brain, and the spinal cord, its roots, and the peripheral nerves. In the latter sites the tumours are usually benign. The brain and spinal cord may also be compressed by tumours arising in adjacent areas, such as the pituitary gland, the spinal column, or the nasopharynx. Tumours destroy the tissue in which they develop, by compressing neighbouring tissue and by increasing intracranial pressure. Those arising outside the nervous system may lead to disease of the brain, spinal cord, nerve, end-plate, or muscle without direct infiltration of these tissues.
Metabolic, toxic, and endocrine disorders
Numerous complications of disease of other organs affect the nervous system. The largest category includes metabolic disorders, many of which have a genetic basis. The most common neural complications are those that result from toxic agents such as bacterial toxins, drugs, and other chemicals. Neural disorders also can result from mineral and electrolyte dysfunction, from abnormal fluid, or from diseases of the endocrine glands (diabetes, thyroid disease), the kidneys, the liver, the lungs (respiratory failure), and the blood (anemia, leukemia).
Vascular diseases
The central nervous system has a high metabolic rate and depends upon a liberal blood supply for nutrition and for clearance of metabolic waste-products. Vascular conditions, including interruption of circulation, disrupt nervous function; if circulation is not restored speedily, irreversible damage to neurons results. (The area of dead nervous tissue is known as an infarct.) The peripheral nervous system is much more tolerant of blood supply loss, called ischemia. Another vascular cause of brain damage is hemorrhage due to rupture of an artery.
Demyelinating and degenerative disease
Demyelinating disease is characteristically scattered throughout the brain and spinal cord, with small foci where the myelin is destroyed and replaced with glial scar tissue. Nerve fibres running through such areas may remain undamaged, but the lack of insulation normally provided by the myelin leads to a blockage of conduction of electrical impulses. In certain very rare diseases, known as leukodystrophies, large areas of demyelination occur in the white matter of the brain as a result of inherited metabolic disorders. Demyelination is also the result of an immune attack upon the central nervous system, which may follow viral infections such as measles, or of immune deficiency states such as pernicious anemia. Schwann cells, which form the myelin surrounding the axons of peripheral nerves, may suffer immune or toxic attack, as in Guillain-Barré syndrome and diphtheria. This also leads to a blockage of electrical conduction. When an injury is primarily to axons, the Schwann cells are also damaged, producing “secondary demyelination.”
Degenerative diseases are characterized by progressive destruction of neurons without evident cause. Such diseases include Alzheimer disease, affecting primarily the cerebral cortex; Huntington and Parkinson diseases, affecting the basal ganglia and cortex; motor neuron disease, affecting the corticospinal tracts and ventral-horn cells; spinocerebellar degenerations, involving long tracts in the spinal cord, the cerebellum and its connections, and sometimes peripheral nerves; and the hereditary neuropathies with no known metabolic basis, in which motor, sensory, or both classes of peripheral nerves degenerate and lose their function. Most such diseases develop after a variable period during which that part of the nervous system subsequently affected apparently functions normally. As research progresses, the metabolic (and often genetic) bases of these diseases are being successively revealed.
Electrical disorders
Electrical disorders present a unique problem of classification. Because the nervous system is a biologic electrochemical complex, it is possible to regard every aspect of its function as an electrical manifestation, but it is primarily the epilepsies that are regarded as expressions of disordered electrical activity. Seizures represent occasional, sudden, rapid, local, and excessive electrical discharges of the gray matter of the brain. There are two main classes, those with a focal origin anywhere within the gray matter and those in which there is no abnormal pathology, but an abnormally low threshold for electrical activation is present. Although certain abnormal movements occasionally have their origin in spinal cord disease, epilepsy is uniquely a brain disease (see below Diseases and disorders: The cerebrum). Narcolepsy, a disorder of sleep mechanisms, is not a variant of epilepsy.
Autoimmune disorders
It is uncertain whether any diseases of the nervous system can properly be regarded as representing an allergic cause in the strict sense of the term, but many conditions characterized by an inflammation of the blood vessels, such as the auto-allergic collagen-vascular diseases, do have such a basis. These, through reduction of blood supply to parts of the nervous system, may induce neurological symptoms.