D. N. Rushton

Vitamins and the Nervous System

With the exception of vitamin B12, folate and thiamine, B-group vitamins and multivitamin preparations are mainly used in neurology as simple, cheap and relatively harmless placebos for patients with an unexplained neuropathy, or with a chronic neurological illness. Despite the lack of evidence of any efficacy here, many vitamins play a vital role in the maintenance of the nervous system. Vitamin A deficiency remains a major cause of blindness in less developed countries, although vitamin A toxicity, due to grossly excessive self-medication, may be commoner than deficiency states in America. In the United Kingdom, pellagra is still seen in lonely old people eating an inadequate diet, and thiamine deficiency, due to alcoholism, is a major health problem throughout the western world. Recently, several reports have suggested that chronic fat malabsorption, resulting in severe and prolonged vitamin E deficiency, can result in spinocerebellar degeneration. Several drugs used in neurology can lead to vitamin deficiency, the best known example being that of pyridoxine deficiency due to isoniazid, although the decarboxylase inhibitors that are widely used in the management of parkinsonism may result in biochemical evidence of niacin depletion, but not clinical pellagra. Vitamin A, vitamin K, niacin and pyridoxine are summarised in Tables 12.1–12.4.

Treatment of Diseases of Nerve and Muscle

Primary muscle disease causes muscle wasting and weakness without sensory change. Disease of the muscle end-plate, myasthenia, causes fatiguable muscle weakness without wasting (at least until the late stages of the illness). Peripheral nerve diseases cause muscle wasting and weakness with peripheral sensory deficit. Unfortunately, many diseases affecting muscles and nerves are not susceptible to specific treatment. However, the resulting weakness and wasting, and sensory change if present, require appropriate symptomatic therapy and the use of mechanical aids. This general management of muscle wasting and weakness will be discussed first.

Drugs and the Nervous System

Neurones possess a variety of basic processes to ensure chemical neurotransmission. All of these processes provide targets for drug-induced manipulation of the nervous system. (a) Neurones synthesise and store one or more neurotransmitters. (b) Neurones release the neurotransmitter into the synaptic cleft in a pulsatile manner in response to impulse flow; but also limit its activity by reuptake into the neurone or by degradation, (c) Neurones regulate their own function through local feedback systems via events occurring in the synaptic cleft or via long loop feedback systems operating through neuronal contacts.

Disorders of Sleep and Wakefulness

Narcolepsy and sleep apnoea are the commonest causes of persistent daytime sleepiness. There are approximately 20 000 people with narcolepsy in the United Kingdom, 100 000 in the United States. The diagnosis of narcoleptic syndrome is established by the history of recurrent daily short sleep attacks in combination with cataplexy, brief episodes of loss of muscle tone and paralysis. Narcolepsy often results from monotony, and cataplexy is usually due to a sudden increase in alertness, with laughter or surprise. About one-half of all subjects also have sleep paralysis, and many describe vivid dreams at sleep onset, or even during wakefulness. In classic cases, the diagnosis is obvious from the history, and also from the finding of at least two sleep-onset REM periods during a multiple sleep latency test (MSLT). The MSLT gives an index of daytime drowsiness, with measurement of the time of sleep onset at 2-h intervals on five occasions throughout the day.

Treatment of Movement Disorders

Movement disorders comprise a large group of neurological conditions characterised by either: (a) slowness and poverty of movement with rigidity, and sometimes rest tremor—the akinetic-rigid syndrome; or (b) abnormal involuntary movements—the dyskinesias. Common causes of these disorders are shown in Tables 5.1 and 5.2.

Drug Treatment of Infections of the Nervous System

Infections of the nervous system are most common with crowding, poverty, malnutrition, or immune paresis such as accompanies malignant diseases, AIDS or the use of immunosuppressive drugs. As a general rule, the earlier the diagnosis and treatment, the better is the outcome. The mortality and morbidity from these potentially curable conditions remain unacceptably high, especially in neonatal meningitis and pneumococcal meningitis in people over 60.

Immunosuppressant and Cytotoxic Drugs, Toxic and Metabolic Disorders

Immunosuppressant drugs, including steroids, are used in many neurological disorders for which an autoimmune aetiology has been suggested. These conditions include myasthenia gravis (p. 152), polymyositis and dermatomyositis (p. 158), as well as generalised autoimmune diseases which involve the nervous system, including systemic lupus erythematosus and polyarteritis nodosa.

Drugs in Neuroendocrinology

Corticosteroids reduce antibody formation, and have an anti-inflammatory effect. The main use of these drugs in neurology is to suppress disease processes. Although corticosteroids are widely used in many different neurological disorders, their value is sometimes uncertain. The main indications are set out in Table 11.1.

Headache, Pain and Raised Intracranial Pressure

Common migraine, tension-vascular headache, tension headache and “ordinary” headache overlap, and clinical diagnosis is not exact. Classic migraine and REM sleep-locked cluster headache are distinct clinical entities that can be easily recognised.

Treatment of Disorders Involving the Autonomic Nervous System

Autonomic failure occurs as a result of preganglionic or postganglionic autonomic neuropathy, or where there is an extensive defect in the central segment of autonomic reflexes, as in tetraplegia, or (rarely) in failure of the sensory limb of the buffer reflexes. Different diseases affect different parts of the autonomic system, resulting in different patterns of autonomic failure. Autonomic defects that are asymptomatic and detectable only by tests are not usually worth treating.