NERVOUS SYSTEM DISEASE

The nature and pattern of the symptoms and physical signs of neurological disease allow inferences to be drawn about the sites of the lesions causing them. The main sites are described below, with notes on some of the clinical features that lead to their localization. Lower-level sites Muscle Muscle disease is frequently hereditaryin which case a positive family history may be obtained. One complaint suggesting muscular involvement in the disease is that of weakness, usually symmetrical and mainly affecting the proximal or girdle muscles. This type of weakness is noticed on climbing stairs, arising from a deep easy chair, brushing the hair, or lifting an object. Facial weakness leads to difficulty in whistling and to drooling of saliva. Weak masticatory muscles tire easily, so that food is chewed with difficulty, while bulbar muscle involvement leads to problems with phonation, articulation, and swallowing. Diseased muscles are often atrophied but they may also swell and be tender or subject to cramp. In the condition known as myotonia they continue to contract even when the patient wants them to relax. any of the diseases or disorders that affect the functioning of the human nervous system. This article discusses those diseases that have organic causes. For a discussion of psychological disorders, see mental disorder. Everything that the human being senses, considers, and effects and all the unlearned reflexes of the body depend upon the functioning of the nervous system. The skeleton and muscles support and transport the body, the heart sends it nourishment through the blood, and the alimentary system and lungs provide the nutrients; but the nervous system contains the epitome of the human beingthe mindand commands all perception, thought, and action. Its disturbance through disease or other malfunction leads to changes felt throughout the body. The most common or important of those diseases are discussed in this section. A distinction is usually drawn between structural or biochemical diseases of the nervous system (the province of the neurologist) and diseases of the mind (requiring the attention of a psychiatrist). This distinction is not, of course, absolute. Many organic brain diseases cause disorders of thought or mood, while the disorders of function that characterize mental disease are profoundly influenced by chemical factors. This section will be confined to those conditions generally regarded as organic nervous disease. The first part describes the methods whereby neurologists obtain information about the problemin other words, the history, the examination of the patient, and the laboratory investigations that can be employed. Next the anatomical sites of neurological disease are described, along with the principles used in localizing a disease within the nervous system. The third part gives an overview of pathological processes. Finally, an account is presented of the diseases of the nervous system, using a general classification based upon the primary or major site of the disease. This scheme is not always possible to follow closely. For example, multiple sclerosis can affect the white matter of the cerebrum, the optic nerves, the cerebellum, or the spinal cord in any patient, so that allocating the disease to any one section must necessarily be arbitrary. Also, metabolic, toxic, inflammatory, and neoplastic diseases may behave similarly. The rule followed here is that the occurrence of various pathologies at different sites are recorded in the discussion of diseases affecting those sites, but a full description is given only in that part dealing with the site that the disease in question affects most consistently. The skull and spine Neural tube defects The primitive neural tube normally closes by the end of the third week of fetal growth, but when it fails to close, severe deficits result. The worst of these is anencephaly, the absence of brain; a cyst replacing the cerebellum is a less severe form of the same problem. At lower levels the spinal canal or cord may also fail to close up. Such defects are known as spina bifida occulta when there is only X-ray evidence of this, meningocele when a meningeal pouch visibly projects through the skin, and meningomyelocele when such a pouch contains elements of the spinal cord or nerve roots. Depending on the level, function of the legs is often severely impaired. Bladder and bowel control is also lost in such cases, and the infants commonly have hydrocephalus as well. Hydrocephalus This progressive enlargement of the head is caused by obstructed drainage of the cerebrospinal fluid, usually at the level of the aqueduct or fourth ventricular roof. Huge enlargement of the ventricles results at the expense of cerebral tissue; shunting of the fluid is required to prevent gross expansion of the skull and death through attrition of the brain. Other congenital malformations in which the head size is abnormal include microcephaly and macrocephaly; in the latter case, expansion of the brain usually follows infiltration in metabolic diseases. In hypertelorism the eyes are set unusually far apart, and in craniostenosis the sutures of the skull do not develop, so that the skull grows abnormally along one or another diameter. In hemiatrophy, one-half of the skull and face may not develop as well as the other, in which case the brain also may be unusually small. Occurring at the junction between skull and neck, platybasia, an abnormal shallowness of the posterior fossa of the skull, is a malformation that may be associated with projection of the vertebral column upward, indenting the base of the skull. (This condition may also occur in association with bony diseases such as osteomalacia and Paget's disease of bone in adult life.) In the Arnold-Chiari malformation, cerebellar or medullary tissue projects downward into the upper cervical spinal canal, causing signs of cerebellar dysfunction, hydrocephalus, or widening of the central canal of the spinal cord with damage to the surrounding fibre tracts. Fusion of the upper cervical vertebrae in the Klippel-Feil anomaly is another malformation, but it does not always produce symptoms. Additional reading Texts on the pathology, diagnosis, and treatment of nervous diseases and disorders include W.R. Gowers, A Manual of Diseases of the Nervous System, 2nd ed. rev. and enlarged, 2 vol. (189293, reprinted 1970); Webb Haymaker and Barnes Woodhall, Peripheral Nerve Injuries: Principles of Diagnosis, 2nd ed. (1953, reprinted 1967); A.B. Baker (ed.), Clinical Neurology (1955 ), with annual revisions published for loose-leaf update; E. Stephens Gurdjian and L. Murray Thomas, Operative Neurosurgery, 3rd ed. (1970); Alexander G. Reeves, Disorders of the Nervous System: A Primer (1981); Webb Haymaker and Raymond D. Adams (eds.), Histology and Histopathology of the Nervous System, 2 vol. (1982); H. Houston Merritt, Merritt's Textbook of Neurology, 8th ed. edited by Lewis P. Rowland (1989); Raymond D. Adams and Maurice Victor, Principles of Neurology, 4th ed. (1989); W. Russell Brain, Brain's Diseases of the Nervous System, 9th ed. by John Walton (1985); and William Pryse-Phillips and T.J. Murray, Essential Neurology, 4th ed. (1991). William E.M. Pryse-Phillips The skull and spine Many disorders of the nervous system cannot be localized to a single site, or they represent the distant effects of disease of other parts of the body. Effects of systemic disease Endocrine diseases Disorders of the hypothalamus may lead to symptoms of autonomic dysfunction, sleep disturbance, and diabetes insipidus (in which large volumes of dilute urine are secreted). Pituitary adenomas may cause acromegaly, in which peripheral-nerve compression may also occur. Overactivity of the thyroid gland causes tremor, muscle weakness, and disturbances of eye movements, while underactivity leads to mental dulling, deafness, difficulty in relaxing muscles, and median-nerve compression. Muscle weakness is seen in overaction of the parathyroid gland; underactivity is associated with seizures. Muscle weakness is also one of the features of adrenal gland dysfunction (both Addison's and Cushing's diseases); both of these conditions also induce abnormal mental states. Diabetes mellitus causes many neurological complications, including peripheral neuropathy (with features of autonomic failure), painful nerve root lesions in the lumbosacral plexus, acceleration of the rate of atherosclerosis with an increased chance of stroke, and damage to the retinas. Hyperinsulinism reduces blood-sugar levels, which may cause coma. Use of oral contraceptives slightly increases the risk of stroke. Evolution and development of the nervous system The study of the evolutionary development of the nervous system traditionally concentrated on the structural differences that exist at various levels of the phylogenetic scale, but certain functional characteristics, including biochemical and biophysical processes laid down early in evolution and amazingly well conserved to the present, can no longer be ignored. Two basic aspects of the evolution of the nervous system must be considered: first, how primitive systems serve newer functions, and, second, how the formation of new systems serves newer functional requirements. Early theories on the evolutionary origin of the nervous system argued for a three-stage process: first, the development of non-nervous independent effectors, such as muscle cells; second, the appearance of non-nervous receptors responding to certain modalities in a receptor-effector mechanism; and finally, the formation of a protoneuron, from which primitive nerves and ganglia evolved. This model is no longer considered valid. In primitive systems there appear to be many examples of non-nervous electrical conduction. For instance, large areas of epithelium covering the swimming bells in the hydrozoan order Siphonophora (which contains certain families of jellyfish) contain neither nerve nor muscle, yet depolarizing potentials between cells of the epithelium have been recorded. Similar examples from other systems in related orders suggest that the evolution of the nervous system may have begun with non-nervous epithelial tissue. The conduction of electrical potentials from one epithelial cell to the next may well have been via so-called tight junctions, in which the plasma membranes of adjacent cells fuse to form sheets of cells. Tight junctions have low electrical resistance and high permeability to molecules. They also occur in great numbers in embryos, suggesting that the electrical potentials of cells joined in this manner serve as a driving force for the movement of ions and even nutritive substances from one cell to the next. These phenomena suggest that electrically mediated junctional transmission is older than chemically mediated synaptic transmission, which would require that some epithelial cells secrete chemical substances. Many investigators believe that neurons originated from endothelial secretory cells that could secrete chemical substances, respond to stimulation, and conduct impulses. Specialization may then have brought about an outer receptor surface and an inner conducting fibre. In fact, neurosecretory cells can propagate action potentials, and many neurons secrete chemical substances, called neurohormones, that influence the growth and regeneration of cells at other sites of the body. Some researchers suggest that neurons first appeared as neurosecretory growth-regulating cells in which elongated processes were later adapted to rapid conduction and chemical transmission by release of transmitters at their endings. There is an amazing consistency in neurotransmitters present in different organisms of a given phylum, although different phyla may show striking differences. Thus, in vertebrates, including fishes, amphibians, reptiles, birds, and mammals, the motor neurons (neurons whose fibres innervate striated muscle) are always cholinergic; in arthropods, on the other hand, they are not cholinergic, although the sensory neurons do secrete acetylcholine. The number of known neurotransmitter substances in the animal kingdom is indeed small, and their presence in more primitive organisms as well as in nervous systems of later vertebrates shows a striking conservation of these substances throughout evolution. If later organisms evolved from single-celled ancestors, then there must have been some system for the transmission of information from one evolutionary stage to the next. These conditions have been defined as: (1) a stable means for encoding, transmitting, and decoding characteristics from one generation to the next, (2) the possibility of alterations in the code taking place by mutation or sexual recombination, and (3) a means of selecting only those characteristics for transmission that are favourable for survival. As mentioned above (see Stimulusresponse coordination), protozoans (single-celled organisms) move toward places that are favourable for survival, such as areas with optimal conditions of light and temperature. As the metazoans (multicelled organisms) developed, entire groups of cells probably tended to move toward favourable conditions, and when the number of cells became very large, a system of internal communicationin effect, a nervous systemdeveloped. Two general types developed: the diffuse nervous system and the centralized nervous system. Diffuse nervous systems The diffuse nervous system is the most primitive nervous system. In diffuse systems nerve cells are distributed throughout the organism, usually beneath the outer epidermal layer. Large concentrations of nerve cellsas in the brainare not found in these systems, though there may be ganglia, or small local concentrations of neurons. Diffuse systems are found in cnidarians (hydroids, jellyfish, sea anemones, corals) and in ctenophores, or comb jellies. However, the primitive nervous systems of these animals do not preclude prolonged and coordinated responses and integrated behaviour to the simplest stimuli. An example is the movement of the sea anemone Calliactis onto the shell of the hermit crab Pagurus in response to a factor present in the outer layer of the empty mollusk shell occupied by the crab. This movement requires integration of the highest order. Most cnidarians, such as those of the genus Hydra, have what is called a nerve neta meshlike system of individual and separate nerve cells and fibres dispersed over the organism. Species of Hydra have two nets, one located between the epidermis and the musculature and the second associated with the gastrodermis. Connections occur at various points between the two nets, with individual neurons making contact but not fusing, thereby forming structures similar to the chemically mediated synapses of vertebrates. Several specializations occur within various species. In Hydra the neurons are slightly more concentrated in a ring near the pedal disk and the hypostome (the mouth), but in jellyfish of a related genus the nerve fibres form a thick ring at the margin of the bell to form through conduction pathways. The nervous systems of cnidarians correspond to their radially symmetrical bodies, in which similar parts are arranged symmetrically around a hollow gut cavity called the coelenteron. In some species nerve fibres course along the radial canals, where there may be arranged sensory bodies, called rhopalia, which contain ganglionic concentrations of neurons. In the sea anemone Metridium some of the nerve fibres are seven to eight millimetres long and form a system for fast conduction of nerve impulses. Such specializations may have allowed the evolution of different functions. Certainly the rapid coordination of swimming movements requires a fast-conducting pathway, while feeding relies on the nerve net. Integrative activity is likely to occur at the sensory ganglia, which may represent the first forms of a centralized nervous system. The terminals forming synapselike structures in nerve nets contain synaptic vesicles that are believed to be packed with neurotransmitters and neuroactive peptides. Peptides present in Hydra nervous systems also exist in mammalian systems as neuromodulators, neurohormones, or even possible neurotransmitters. Transmission in the nerve net is relatively slow compared with that in other nervous systems (0.04 metre per second in radial fibres of Calliactis compared with 100 metres per second in some fibres of the dog). Many repetitive stimuli may be required to elicit responses at these synapses. Long refractory periods are also characteristic of nerve nets, having durations about 150 to 300 times those seen at mammalian nerve fibres. Finally, pacemaker systems are present in animals with nerve nets. In the sea anemone Metridium these systems are expressed in a series of spontaneous rhythmic movements that occur in the absence of any detectable stimulus. The question remains whether the movements originate from a command neuron or group of neurons or whether they arise without neuronal stimulation. It has been postulated that pacemaking cells were present in epithelial conducting systems known not to be nervous but that eventually evolved into neuronal tissue. Form and function of nervous systems Transmission of information in the nervous system In the nervous systems of animals at all levels of the evolutionary scale, the signals containing information about a particular stimulus are electrical in nature. In the past the nerve fibre and its contents were compared to a metal wire, while the membrane was compared to insulation around the wire. This comparison was erroneous for a number of reasons. First, the charge carriers in nerves are ions, not electrons, and the density of ions in the axon is much less than that of electrons in a metal wire. Second, the membrane of an axon is not a perfect insulator, so that the movement of current along the axon is not complete. Finally, nerve fibres are smaller than most wires, so that the currents they can carry are limited in amplitude. The ionic basis of electrical signals Ions are atoms or groups of atoms that gain an electrical charge by losing or acquiring electrons. For example, in the reaction that forms salt from sodium and chlorine, each sodium atom donates an electron, which is negatively charged, to a chlorine atom. The result is sodium chloride (NaCl), composed of one positively charged sodium ion (Na+) and one negatively charged chloride ion (Cl-). A positively charged ion is called a cation; a negatively charged ion, an anion. The number of charges carried by an ion is called its valence. Na+ and Cl-, which respectively lose and acquire one electron, have a valence of one, while calcium ions (Ca2+), which lose two electrons, have a valence of two. The electrical events that constitute signaling in the nervous system depend upon the distribution of ions on either side of the nerve membrane. Underlying these distributions and their change are crucial physicochemical principles.