413 Postgrad Med J: first published as 10.1136/pgmj.35.405.413 on 1 July 1959. Downloaded from POLYNEURITIS By G. S. GRAVESON, M.A., M.D., F.R.C.P. Consultant Neurologist, Wessex Regional Hospital Board (From the Southampton General Hospital) Diseases affecting the lower motor and sensory acid and vitamin B.I2. Thiamine is a constituent neurones, diffusely and usually symmetrically, are of the coenzyme cocarboxylase, which is necessary grouped together under the title polyneuritis. The for the oxidation of pyruvic acid formed in the term is imprecise, for many of these diseases affect metabolism of glucose by nerve cells. It is also structures other than peripheral nerves, e.g. concerned in the synthesis of acetylocholine in spinal nerve cells, roots and muscles, and few of nerve fibres. Its deficiency, therefore, results in them are really inflammatory disorders. To over- neuronal degeneration and the accumulation of an come this inaccuracy, such terms as polyradiculo- excess of pyruvate in the blood. This may be neuropathy and neuromyopathy have been coined present in the fasting state or it may be brought but the older word still serves, with better out by a loading dose of glucose. Joiner, McArdle euphony perhaps, provided it is used merely in and Thompson (1950) describe the use of such aProtected by copyright. the sense of a condition in which lesions of peri- 'pyruvate metabolism test ' in the investigation of pheral nerves occur. Its retention may be ad- cases of polyneuritis. Lack of thiamine may be a visable, too, until such time as the pathogenesis of contributory factor in the polyneuritis of chronic the various types of the disease have been more alcoholism and in those cases which complicate fully elucidated. From a clinical viewpoint, the chronic disease of the gastro-intestinal tract. Its disease is a syndrome, easily recognized as such, action as a coenzyme has to be integrated with that but often requiring much time and care in the of another enzyme, lipoic acid (Sinclair, I956). investigation of its aetiology. Classification of the This substance is thought to be formed in the disorder on aetiological lines, e.g. toxic, metabolic, liver and it has the property of forming stable infective types, etc., is usual in neurological texts, compounds with a variety of organic and inorganic but this cuts across pathogenesis and it seems substances, e.g. arsenic, mercury, carbon disul- preferable to attempt a division on pathological phide, acetaldehyde and acetoacetate. Sinclair grounds. Three main groups may be distin- suggests that the polyneuritis produced by such http://pmj.bmj.com/ guished: (a) parenchymatous, (b) interstitial, and substances is similar to that of thiamine deficiency (c) vascular (Greenfield, 1958). in so far as the same underlying enzyme systems are affected. He also thinks that diabetic poly- (a) Parenchymatous Types of Polyneuritis neuritis may be in part due to the inactivation of These are two in number: (i) those in which the lipoic acid by ketones. neurone degenerates as a whole or in its peripheral Pantothenic acid as part of coenzyme A is part-primary neuronal degeneration; and (ii) those intimately concerned with the metabolism of on September 30, 2021 by guest. in which demyelination of the nerve fibres occurs pyruvate as well as thiamine, but it is so widely in segments-segmental demyelinative neuropathy distributed in food that its deficiency in man is (Fisher and Adams, 1956). The first comprises unsubstantiated. It has been claimed to cure the those types of polyneuritis in which some meta- ' burning feet' syndrome, but this is doubtful, bolic or dietetic deficiency results in degenerative and it has been used with apparent benefit in the or atrophic changes. The classical example is treatment of vestibular neurone damage caused beri-beri, and it was from experimental work in by streptomycin. connection with this disease that the B group of Pyridoxine deficiency in animals produces inter vitamins was discovered. In animals, several of alia epileptic fits and peripheral nerve degenera- these vitamins seem necessary for the preservation tion. In man this vitamin forms a stable com- of an intact peripheral nervous system; in man, pound with isoniazid (I.N.A.H.), which blocks its only five are of relevant clinical importance- action. Hence a polyneuritis may occur and, in thiamine, pantothenic acid, pyridoxine, nicotinic fact, in this country, I.N.A.H. is probably the 414 POSTGRADUATE MEDICAL JOURNAL July 1959 Postgrad Med J: first published as 10.1136/pgmj.35.405.413 on 1 July 1959. Downloaded from commonest cause of a chemically induced Refsum's disease and primary infection of nerves neuropathy. such as in leprosy and trypanosomiasis. Deficiencies of nicotinic acid and vitamin B.I2 also produce peripheral neuropathies, usually (c) Vascular Types of Polyneuritis overshadowed by spinal cord changes, in pellagra Peripheral nerves may be damaged in generalized and subacute combined degeneration of the cord vascular disease of the limbs-atheroma, Buerger's respectively, but the exact pathogenesis is not yet disease, frostbite and immersion foot. The known. Even less is known of the cause of the nutrient arteries of nerves may, however, be polyneuritis associated with carcinoma, reticulosis specifically affected, for example, in polyarteritis and sarcoidosis, but it is also thought to be due to nodosa. This results in necrosis of fibres distal some metabolic disturbance. to the segment affected. Such changes may be Finally, primary degeneration of peripheral diffuse, giving rise to a symmetrical polyneuritis, nerves may occur as an hereditary disease-pero- or they may be scattered irregularly to produce a neal muscular atrophy (Charcot-Marie-Tooth's series of peripheral nerve palsies-mononeuritis disease). Presumably again the fault is biochemi- multiplex. cal, though nothing is known of its nature. This grouping of types of polyneuritis cannot The second type of parenchymatous poly- be extended to all varieties of the disease. So neuritis is segmental demyelinative neuropathy. little is known of the pathogenesis of some that In this condition, involvement of nerve fibres is accurate classification is impossible. This applies patchy and in the early stages limited to internodal in particular to one of the most common-diabetic segments of the myelin sheath, with preservation polyneuritis. The pathological changes here of the sheath proximal and distal to the lesion. suggest that possibly all three types may be seen in Axon degeneration does not occur until a late this disease. The accompanying table summarizes stage is reached and, therefore, in less severe cases this classification and is modified from GreenfieldProtected by copyright. recovery can occur. This curious pattern of in- (1958). volvement probably occurs because the primary toxic damage is to the sheath of Schwann and it is Clinical Diagnosis seen in the polyneuritis of diphtheria, lead and By and large, polyneuritis presents no great acute porphyria. problem in diagnosis. Variations in symptoms and signs occur, of course, between different types (b) Interstitial Types of Polyneuritis of the disease but these are quantitative rather This group comprises inflammations of the peri- than qualitative and depend on the tempo of events and endoneurial tissues and the pressure effects of and relative differences in the involvement of acute and chronic oedema on nerves and spinal motor and sensory fibres. Only rarely is the roots. Its most important varieties are those distribution of lesions of diagnostic help, e.g. the diseases which appear to have an allergic aetiology peculiar ciliary and palatal paresis of diphtheritic -acute infective polyneuritis (the Guillain-Barre polyneuritis. This discussion, therefore, will be http://pmj.bmj.com/ syndrome), polyneuritis complicating serum and mainly concerned with general principles only. vaccine therapy and possibly acute brachial radi- Motor nerve involvement produces those features culitis (neuralgic amyotrophy). Only in the first of a lower motor neurone lesion-weakness, of these have adequate pathological studies been wasting and a diminution or loss of tendon reflexes. made (Haymaker and Kernohan, 1949). The Sensory nerve involvement is more variable in its initial change is one of oedema of the roots and presentation depending on the type of fibre proximal parts of the spinal nerves, followed by damaged. Symptoms consist of pain, paraes- degeneration of myelin sheaths and axons and thesiae, numbness and unsteadiness, objectively in on September 30, 2021 by guest. later by lymphocytic infiltration. The allergic loss or impairment of the modalities of touch, hypothesis has been strengthened by the work of pain, temperature, vibration and joint sense, to- Waksman and Adams (I955, 1956), who were able gether with an increase of muscle tenderness. In to produce an experimental allergic neuritis in most types of polyneuritis, the longest nerve animals by the injection of homologous peripheral fibres are earliest affected so that these symptoms nerve tissue with suitable adjuvants. The appear distally in the extremities and usually in the sequence of pathological events was similar to that legs before the arms. On the motor side this gives in acute infective polyneuritis. It is in this group rise to a bilateral foot drop with a steppage gait, of disorders that steroid therapy has proved of and in the upper limbs to weakness of hand great value. muscles and wrist and finger drop.