Postgrad Med J: first published as 10.1136/pgmj.41.476.347 on 1 June 1965. Downloaded from POSTGRAD. MED. J. (1965), 41, 347 THE NON-DYSTROPHIC JOHN PEARCE, M.B., M.R.C.P., Department of , The General Infirmary, Leeds. THE TERM '' is applied to any disorder Polymyositis may affect people of any age, of the muscle fibre, the muscle fibre membrane, but the age of onset is from 30 to 60 in 60% the myoneural junction, or the muscle connect- of cases. The chief symptom is weakness of ive tissue. 'Non-dystrophic myopathy' includes proximal muscles of the arms and/or legs all diseases of muscle excluding those genetically in every case. Distal muscles are affected in determined primary degenerative myopathies, one third, and the neck muscles in two thirds collectively known as . of patients. Fever, muscular pain and tenderness TABLE 1 are seen most often in the more acute forms, CLASSIFICATION OF NON-DYSTROPHIC MYOPATHIES and their absence should not lead to neglecting 1. Inflammatory Polymyositis as a Myopathy Connective tissue disorders polymyositis possible diagnosis. Other inflammatory mvopathies Acute polymyositis is not common, but may 2. Metabolic Familial periodic progress rapidly and involve the respiratory Myopathy Muscle glycogenoses muscles, sometimes with a fatal termination Myoglobinuric myopathies within a few weeks or months. Myopathies associated with Subacute and electrolyte imbalance chronic forms are more frequent, and present Unclassified myopathies with a progressive weakness and moderate of shoulder 3. Endocrine Thyrotoxicosis wasting and pelvic girdle muscles. Myopathy Cushing's Syndrome There is sometimes no systemic disturbance, Steroid myopathy and pain and tenderness are lacking. All prox- Hypothyroidism imal muscles tend to be affected, and to an by copyright. Hypoadrenalism equal extent. In patients with the disease of 4. Neoplastic Carcinoma long standing, fibrous contractures, and cal- Myopathy Reticuloses cinosis of subcutaneous and muscle tissues 5. The Myasthenic may develop. Syndrome Thyrotoxic myasthenia Myopathic-myasthenic Dysphagia, Raynaud's phenomenon, joint syndrome of carcinoma pains, and skin rashes are common accompani- ments of muscle weakness, and are important Inflammatory Myopathies clues to the presence of polymyositis. The http://pmj.bmj.com/ Polymyositis acuteness of the onset, and the rate of pro- This term encompasses a group of inflam- gression are enormously variable, and spontane- matory disorders of muscle of varied aetiology. ous but usually incomplete remissions are In some patients the condition is confined to seen. muscle tissues but in most occasionally instances there is The skin lesion of dermatomyositis is seen evidence of some systemic disturbance indicat- in 40% of patients (Pearson, 1964). A violace- ing that the myopathy is only part of a more ous is and erythema characteristic, involves on September 26, 2021 by guest. Protected generalised disease of connective tissues. the Accordingly, polymyositis is classified on a particularly eyelids, face and extensor clinical basis, until our understanding of this aspects of the arms. The heliotrope scaling of disorders as a whole is more eruption of the upper eyelids is virtually group complete. A TABLE 2 diagnostic. diffuse erythema and scaling CLASSIFICATION OF INFLAMMATORY MYOPATHIES eruptions are common but non-specific. Tighten- (Modified from Walton and Adams, 1958) ing of the skin over the face, or the distal (i) Polymyositis with purely muscle involvement- phalanges, which appear tapered and shiny, Acute, Subacute, Chronic. and show small (ii) Polymyositis with connective tissue disease or may telangiectatic patches, dermatomyositis, but muscle involvement are characteristic of the skin involvement of dominant. systemic sclerosis, of which polymyositis may (ii) Polymyositis with connective tissue disease or be symptomatic. In patients of middle or old dermatomyositis, but major involvement is of or primary disease and muscle weakness is not age, polymyositis dermatomyositis may be striking. secondary to neoplastic lesions, and this is (iv) Polymyositis complicating malignant disease. discussed in a later section. Postgrad Med J: first published as 10.1136/pgmj.41.476.347 on 1 June 1965. Downloaded from 348 POSTGRADUATE MEDICAL JOURNAL June, 1965 Polymyositis can usually be distinguished degeneration or necrosis of muscle fibres, (2) from muscular dystrophy by the following basophilic areas of regeneration with swollen features: vesicular nuclei, (3) infiltration of inflammatory (i) Polymyositis is more common in females cells. Varying degrees of phagocytosis and than males, and spontaneous remissions occur. interstitial fibrosis are also common. In childhood dystrophy males predominate, Treatment consists of high doses of pred- and progression though slower, is usually re- nisone, commencing with 20 mg. tds, which lentless without a true remission, although should be reduced very slowly only when periods of temporary arrest occur. considerable clinical improvement has occurred. (ii) Muscle involvement is diffuse in poly- It may take up to 2-3 months before ameliora- myositis, but tends to be patchy and selective tion commences. Thereafter the drug should in dystrophy. be continued for 1-2 years before it is totally (iii) Weakness of the neck muscles, dys- withdrawn. If a should the dose and skin rashes are common relapse occur, phagia in poly- has to be increased until the symptoms are myositis, but rare in muscular dystrophy. again controlled. Occasionally ACTH 60-80 (iv) In polymyositis weakness often exceeds Units daily by intramuscular injection will the wasting of muscles, and in the early stages afford a remission unobtainable by prednisone. the reflexes are preserved; in dystrophy the In a series of 52 patients treated by Barwick wasting usually parallels the degree of weakness, and Walton (1963), 34 recovered or improved, pseudohypertrophy is common, and the re- and the remainder were unchanged, worse, or flexes disappear early in the disease (Walton, died. This included Group IV patients with 1961). malignancy, all of whom fared as anti- Investigations are invaluable in establishing cipated. badly the diagnosis. The ESR is sometimes elevated, but this is inconstant; an elevated gamma Polymyalgia Rheumatica globulin fraction of serum proteins associated This is probably an inflammatory disorder with a decreased albumin fraction (Gavrilescu of the intramuscular connective tissue, not by copyright. in- and Small, 1962) is found in over half the cases. volving muscle fibres (Walton, 1964). The (EMG) reveals low- patient is over the age of 60, and has severe, amplitude polyphasic action potentials, on unrelenting aching pains around the neck, maximal voluntary contraction indicating a shoulders and upper arms, sometimes also in- myopathy. Fibrillation and 'saw tooth' poten- volving the buttocks and thighs. Movements tials, and a pseudomyotonic pattern are also of shoulder and hip joints are limited, but frequently seen, and are thought to be associated solely by pain, not by muscular weakness or with muscle fibre irritability. Electromyography arthritis. Physical examination is otherwise is however a random sampling method, and negative, but the ESR is invariably overhttp://pmj.bmj.com/ normal patterns may be obtained for this 50 mm/hr, and a mild normochromic anaemia reason, unless many different areas are sampled. is a common accompaniment. (Gordon, 1960; With this reservation, EMG studies show evi- Bagratuni, 1963). High levels of plasma fib- dence of myopathy in 80% of patients. rinogen (>400 mg./100 ml.) and of alpha- Serum aldolase and SGOT are elevated in 2 globulin values are frequently found. Alestig about half the patients, especially those with and Barr (1963) found evidence of arteritis in the most active disease (Barwick and the temporal arteries in seven out of ten cases, Walton, on September 26, 2021 by guest. Protected 1963). Serum is elevated in and 16 of 21 biopsies of the temporal arteries only one third of cases. (Pearce, Pennington showed similar signs of arteritis in a series and Walton, 1964). These changes are helpful reported by Hamrin, Jonsson, and Landberg in distinguishing polymyositis from endocrine (1964). These findings suggest that giant cell and metabolic myopathies in which normal arteritis and polymyalgia rheumatica are two values are usual. Serum creatine kinase estima- clinical variants of the same disease-an tions are of limited value in separating poly- arteritis of the elderly. The response to pred- myositis from dystrophy unless a small eleva- nisone is dramatic in all patients with poly- tion or normal level are found, which would myalgia, and spontaneous remission occurs favour polymyositis. within approximately two years. Muscle biopsy should be performed on a Connective Tissue Diseases and other proximal muscle-e.g., deltoid or matory Myopathies Inflam- in which EMG studies have not beenquadriceps,performed. The consist of Involvement of muscle is a fairly common typical changes (1) Primary pathological finding in many of the so called Postgrad Med J: first published as 10.1136/pgmj.41.476.347 on 1 June 1965. Downloaded from June, 1965 PEARCE: The Non-Dystrophic Myopathies 349 'auto-immune' collagen diseases (Sokoloff, an autosomal dominant with a predilection for Wilens, Bunim and McEwen, 1950). Signs males. The hypokalaemic variety is characterised of myopathy are however infrequent. A chronic by attacks of flaccid paralysis of the limbs and progressive proximal amyotrophy is seen in trunk but sparing the muscles of smiling, Sj6gren's syndrome, and a 'focal nodular myo- swallowing, talking and breathing. The attacks sitis' is found in biopsies of muscle in patients commence in the second decade, but decrease in with systemic lupus erythematosus, systemic frequency after the middle thirties. Paralysis sclerosis, rheumatoid disease, and polyarteritis may be partial or complete, and lasts from nodosa, These pathological lesions are some- 6-24 hours, followed by total recovery. Attacks times however, unaccompanied by clinical are precipitated by rest after exercise, a high signs of myopathy, and the histological changes carbohydrate meal, anxiety and cold. During are not of value in differentiating the different the attack the serum potassium falls to below primary collagen disease with which they are 3mEq/1, and it has been shown that potas- associated. A curious 'vacuolar myopathy' is sium moves into the muscle cells and this is occasionally seen in systemic lupus erythem- associated with dilatation of the endoplasmic atosus (Pearson and Yamazaki, 1958) and reticulum (Shy, Wanko, Rowley and Engel, appears to be specific. Ischaemic lesions of 1961). Attacks may be induced by administer- muscle due to an underlying arteritis may ing insulin and glucose. The current view is produce patchy and asymmetrical weakness, that this disorder is due to an inherited enzyme wasting and tenderness of muscles in any of defect resulting in an excessive accumulation of these disorders. The typical non-caseating indiffusible products of carbohydrate meta- granulomata of sarcoidosis can occur in the bolism with a consequent shift of potassium muscles of patients with evidence of systemic and water into the cells (McArdle, 1956, 1964). sarcoidosis and a proximal myopathy, which Treatment consists of intraveneous potassium clinically resembles chronic polymyositis has chloride (5-15 for the acute been described in such gm) attack, and patients (Crompton and oral potassium salts, or spironolactone as inter- by copyright. MacDermot, 1961). The pathological sarcoid val therapy. granulomata, are however much more common Hyperkalaemic (Gamstorp, in patients with no clinical signs of myopathy 1956) usually begins in the first decade, and and indeed may afford a useful aid to diagnosis, the attacks are shorter in duration, lasting for in conjunction with the clinical signs, biopsy less than two hours. The pattern is similar, findings from glands and liver and the Kveim but attacks are precipitated immediately after test. exercise, or by ingestion of food with a high Although it can be seen that focal patho- potassium content. Some show lesions in the muscles of of patients evidence logical patients with , which may be limited to the http://pmj.bmj.com/ the diseases associated with disordered immune- ocular muscles (Van't Hoff, 1962) relating this mechanisms are fairly frequent, it will be condition to paramyotonia. During an episode appreciated that such lesions are often non- of paralysis, the serum potassium is elevated specific in type. The clinical picture is of a to more than 5mEq/1 but weakness may proximal myopathy, usually in an ill patient, occur at lower levels. Evidence exists (MoArdle which may be accompanied by a polyneuro- 1962; Gamstorp, 1962) that there is a leak of pathy, or mononeuritis multiplex, as well as by potassium from muscle cells, and myopathic evidence of multiple system involvement, a changes are seen electromyographically during on September 26, 2021 by guest. Protected high ESR abnormal electrophoresis, and an episode of weakness; furthermore it has sometimes by findings indicative of the under- been suggested that an abnormally low resting lying disease, e.g., LE cells, Waaler-Rose tests. membrane potential is associated with, though The occurrence of such lesions, and the clinical not necessarily caused by the leakage of intra- overlap between the diseases which they com- cellular potassium. plicate and polymyositis is striking, and is at Treatment consists of chlorothiazide 0.5g. least suggestive that polymyositis itself falls daily to produce a deficit of body potassium; into this group of disorders. dichlorphenamide 50 mg daily is also most effective in reducing the frequency and severity Metabolic Myopathies of attacks. Familial Periodic Poskanzer and Kerr (1961) have described a Paralysis normokalemic with Patients afflicted by this of disorders variety, attacks lasting for occur group several days. The serum potassium is normal, sporadically, or may inherit the trait as attacks were precipitated by oral potassium, Postgrad Med J: first published as 10.1136/pgmj.41.476.347 on 1 June 1965. Downloaded from 350 POSTGRADUATE MEDICAL JOURNAL June, 1965

but improvement occurred following large deficiency of myophosphorylase has been con- doses of salt, or of salt retaining steroids e.g., clusively demonstrated in these patients (Pear- fludrocortisone, 0.1 mg. daily. The diagnosis son, Rimer and Mommaerts, 1961). Oral of periodic paralysis can usually be made on fructose, 50-100 g. prior to exercise diminishes the history if other members of the family are the symptoms. The condition is probably not involved. The precipitating factors described progressive in the absence of permanent give a clue to the variety of potassium im- muscular weakness and wasting, and in patients balance, and confirmation is obtained by without myoglobinuria. inducing an attack and by assessment of the electrolytes and the electrophysiological state Myoglobinuric Myopathies during such an attack. The response to therapy Myoglobin in the urine renders the colour is a further useful point. It should be re- red to chocolate brown; the urine gives a posi- membered that occasionally periodic paralysis tive guaiac test, but is not fluorescent, and may be symptomatic of thyrotoxicosis, and in contains no red cells. These features distinguish such circumstances the attacks respond to the myoglobinuria from haemoglobinuria, porphy- specific treatment of the underlying condition. ria, and haematuria. Myoglobinuria may occur Glycogen Storage Diseases of Muscle transiently in any acutely destructive lesion of muscle and is most frequently seen in crush This group of conditions is characterised by injuries, after extreme exertion, and in Haff a defect of one of the enzymes essential to disease-a toxic myolysis following ingestion normal glycogen metabolism. At least six of fish contaminated by an unidentified toxin varieties are known (Thomson, MacLaurin and in Germany. Prineas, 1963), and they may involve the liver, Idiopathic Paroxysmal Myoglobinuria pro- kidney, myocardium or . In duces acute attacks of cramp, pain, weakness children with muscular involvement, profound and tenderness of skeletal muscles, which when weakness and are apparent usually severe can produce prostration and respiratoryby copyright. from infancy. Adult patients have more recently paralysis (Borman, Davidson and been described who with weakness Blondheim, present of 1963). Attacks last 2-3 days and are precipitated - the limbs and muscle pains after exercise, or by exercise, or by infection. Rest and alkalini- with extremes of temperature (Holmes, Hough- sation of the urine are the only important points ton and Woolf, 1960). Investigations show a in therapy, unless acute renal failure occurs failure of elevation of blood lactic acid after which merits in its own ischaemic exercise of the limb, and abnormalities therapy right. of anaerobic glycolysis of muscle homogenates Myopathies Associated with Electrolyte can Imbalance be demonstrated in vitro on biopsy material. http://pmj.bmj.com/ Abnormal collections of PAS positive glycogen Hypokalaemia may be secondary to diarrhoea, can be seen in subsarcolemmal aggregations in , steroids, diabetic coma, muscle biopsies. aldosteronism, and to a potassium-losing The best known of this group is McArdle's nephritis. The usual clinical features are apathy, Syndrome (McArdle, 1951). He reported a 30- delirium, or muscle man who suffered from stupor, twitching, and car- year-old muscular diac arrhythmias. In severe hypokalaemia a pain, weakness and stiffness after exercise which widespread flaccid of all muscles paralysis may on September 26, 2021 by guest. Protected was relieved by rest. After repeated gripping occur; in the early stages this may be curiously with his hands he was unable to extend the selective in distribution, and the reflexes are fingers. These symptoms dated from childhood. preserved; in a short space of time a total Subsequent cases have been reported, some areflexic flaccid tetraparesis results. A low with occasional myoglobinuria. In these patients serum potassium, and the typical ECG changes there exists a failure of the normal three to confirm the diagnosis. fourfold increase of blood pyruvate and lactate, Hyperkalaemic paralysis occur in acute following ischamic exercise, which together with renal may the oliguric failure, or following massive in- subsarcolemmal aggregations of glycogen travascular haemolysis. A flaccid with help to confirm the diagnosis. Such loss of reflexes paralysis be patients may is usually of fairly sudden on- misdiagnosed as having peripheral vascular set: speech, swallowing, and be disease, sciatica, or psychoneurosis. Schmid and in respiration may and Hammaker involved, the early stages a curious (1961) have shown that mental attitude of hostility and resentment is McArdle's syndrome is due to a single com- observed. The cardiac muscle is invariably pletely recessive autosomal gene, and a specific affected and cardiac arrhythmias and arrest are Postgrad Med J: first published as 10.1136/pgmj.41.476.347 on 1 June 1965. Downloaded from June, 1965 PEARCE: The Non-Dystrophic Myopathies 351 the usual cause of death. Intravenous calcium It is clear that the electromyographic and gluconate or insulin and glucose should be pathological abnormalities are not constantly given urgently when the diagnosis has been related to the severity of the myopathy. This confirmed by the estimation of serum potassium, is probably due to the patchy distribution of and by the ECG. the myopathic process, and the random tech- A proximal myopathy with preservation of re- niques of sampling which are utilised. Granular flexes has been observed in hyperparathyroid- degeneration, cedema and cellular infiltration ism, and in renal tubular acidosis (Henson, of connective tissue, have been reported (Sato- 1965). A similar clinical picture has been yoshi and others, 1963) but frequently only recorded in hypocalcaemic states of varied non-specific changes are seen (Adams, Denny- atiology, and these conditions can closely re- Brown, and Pearson, 1963). A complex meta- semble chronic polymyositis. (Richet, Sourdel bolic defect, involving catabolism of all body and Percola, 1937; Pearce, 1965). protein reserves, and a separate specific in- Unclassified hibitory action of thyroxine upon muscle Myopathies creatine kinase, are probably responsible for (Shy and Magee, 1956; chronic . Treatment of the Engel, Foster, Hughes, Huxley and Mahler, thyrotoxicosis totally reverses the myopathy, 1961) is a curious non-progressive myopathy a fact in contrast to the effect of treatment upon producing hypotonia, weakness and impaired endocrine exophthalmos. The cause of this latter motor skills in infancy. The centre of the condition is obscure but is probably related muscle fibres show a dense amorphous cylinder to a specific 'exophthalmos producing substance' of PAS positive material, which has been shown secreted by the anterior pituitary. Seen in asso- to be lacking in oxidative enzymes and phos- ciation with pretibial myxoedema and thyroid phorylase. There is little doubt this is a real acropachy, it tends to progress most rapidly entity, but its place in the classification of con- after thyroidectomy or antithyroid drug therapy, genital myopathies is uncertain. especially in male patients over the age of 40. by copyright. has been recorded on Some response to large doses of thyroxine and two occasions. The clinical picture is of a prox- prednisone is usual, but irradiation of the imal myopathy with involvement of spinal pituitary, orbital decompression, or hypophy- and abdominal muscles, but a less rapid pro- sectomy have to be considered, in conjunction gression than seen in muscular dystrophy. with tarsorrhaphy in the refractory case, to Both cases ((Engel, Wanko, and Fenichel, 1964) avoid corneal ulceration. have shown in the smaller muscle fibres, col- Thyrotoxicosis is a rare cause of myasthenia lections of rod-shaped fibrils of a protein in young people (Drachman, 1962). The thyro- material, related to myosin. The natural history toxicosis develops before, or at the same time http://pmj.bmj.com/ and nosological status of nemaline myopathy as the myasthenia, and one remarkable instance are unknown. of the two diseases occuring in sisters has been Endocrine recorded (Greenberg, 1964). It seems likely Myopathies that the disorder glorified by the name of Thyroid Myopathies 'acute thyrotoxic myopathy' is in fact thyro- Thyrotoxicosis in the untreated state is fre- toxicosis and the bulbar syndrome of thyrotoxic quently accompanied by weakness and some- myasthenia. Both conditions

require specific on September 26, 2021 by guest. Protected times wasting of the muscles of the shoulder therapy, but surgery in the myasthenic patient and pelvic girdles. Difficulty in lifting objects is a calculated hazard. Periodic paralysis has to high shelves, trouble in climbing stairs, and been mentioned as an occasional complication rising from low chairs are common complaints. of which responds to treat- These focal muscular symptoms are easily ment of the primary disease. masked by the general fatigue of the patient, A myopathy is an occasional occurrence in but clinical signs and a myopathic pattern on hypothyroidism, in which however pseudomyo- electromyography are found in 80% of patients tonic tendon jerks are very common. The (Havard, Campbell, Ross and Spence, 1963). myopathy is characterised by diffuse weakness, In a series of 240 thyrotoxic patients, Satoyoshi slowness of movement and enlargement of and his colleagues (1963) found moderate or affected muscle groups. In the adult this is severe weakness in 60%, and gross focal wast- known as Hoffman's syndrome, and despite ing in 7%. Clinical signs were most frequent the pseudomyotonic reflexes, there is no electri- in patients over the age of 40, and in those with cal evidence of myotonia, and there are no hyperthyroidism of longest duration. constant pathological changes in muscle biop- Postgrad Med J: first published as 10.1136/pgmj.41.476.347 on 1 June 1965. Downloaded from 352 POSTGRADUATE MEDICAL JOURNAL June, 1965 sies, (Adams, Denny-Brown and Pearson, non-metastatic neurological syndromes associ- 1963). Thyroxine in adequate doses reverses ated with neoplasm have been reported. These this myopathy. include (Brain, 1963; Croft and Wilkinson, 1963; Mancall and Rosales, 1965), the follow- Pituitary and Adrenal Myopathies ing syndromes: - In the early stages of acromegaly, there 1. A subacute cerebellar syndrome occurs a hypertrophy and increase in power 2. A pure sensory, pure motor, or mixed of skeletal muscles. In the later stages, when polyneuropathy hypopituitarism supervenes, generalised muscu- 3. Progressive dementia or depression lar weakness is common. It has been claimed 4. Progressive multifocal leucoencephalo- that characteristic crescents, or 'half-moons' pathy-usually associated with a malig- are seen in specially stained sections from nant lymphoma muscle biopsies in acromegalics, and in patients 5. Acute necrotising myelopathy with thyroid disorders (Kirchheiner, 1962). 6. The myopathic-myasthenic syndrome These half moons are thought to be collections The myopathy is characterised by an atro- of muco-polysaccharides, and have been related phic paresis, most marked in the proximal to the increased thyrotropin stimulation in muscles of the limbs, and trunk. Pelvic or these diseases. These findings have yet to find shoulder girdle muscles may be affected, and general acceptance. often both. A lordotic waddling gait has been A proximal myopathy is common in recorded, and occasionally weakness of the Cushing's Syndrome. Weakness and wasting neck muscles is present. (Henson, Russell, of proximal muscles and diminished reflexes are and Wilkinson, 1954). The tendon reflexes seen, and are accompanied by the well known are depressed, and fasciculation is not seen. cutaneous atrophy, bruising, stria, and truncal The condition is insidious in evolution, and a obesity. Since Muller and Kugelberg (1959) downhill progression may on occasion be described this syndrome, many patients treated interrupted by spontaneous but fleeting im-by copyright. with corticosteroids have exhibited identical provement. The myopathy commonly ante- features. Steroid myopathy (reviewed by Gold- dates the presentation of the neoplasm, or may ing, Murray, Pearce and Thompson, 1961) is follow it months or years later. related largely to the dose of steroid given and A proportion of these patients exhibit myas- the duration of the therapy. However it is thenic symptoms of muscle fatiguability. A particularly common following the administra- partial response to neostigmine is seen, but tion of the 9-alpha-fluorinated steroids triam- this is far less impressive than the dramatic cinolone, dexamethasone, and fludrocortisone; response in myasthenia gravis. Such patients electromyography shows a slight reduction of are abnormally sensitive to decamethonium tohttp://pmj.bmj.com/ the interference pattern, increased numbers of which cases of myasthenia gravis are resistant. small potentials with reduced amplitude and Potentiation of muscle power, following exer- duration, and increased numbers of short dura- cising through a period of fatigue ("second- tion polyphasic potentials. Histology shows wind phenomenon") is a curious finding. It is remarkably little abnormality. Cessation of accompanied electrically, by a post-tetanic in- steroid therapy has in the writer's experience crement in the amplitude of evoked action been total invariably accompanied by recovery. potentials produced by stimulating motor on September 26, 2021 by guest. Protected It has been alleged that there exists a myo- nerves at rates of more than 50 per second. pathy in rare examples of Addison's disease These differences between the myasthenic- with a specific tendency to develop flexion myopathic syndrome of carcinoma and myas- contractures. It seems probable that these signs thenia gravis should be sought in patients are due to a biochemical disorder of tendons presenting with myasthenia-particularly in and fascia, and not to any specific myopathy. later life. Similarly, a carcinomatous myopathy In all the endocrine myopathies, serum without myasthenia may closely mimic poly- creatine kinase levels are normal, and the diag- myositis. The current view is that this syn- nosis is not difficult if the underlying disease drome is a reaction of muscle tissue to an is detected. (Pearce and others, 1964). auto-immune mechanism directed against an antigen in the muscle or in tumour tissue; Neoplastic Myopathy definitive proof of this aetiological hypothesis Since the pathological finding of a myopathy is however still lacking. Of the contributory in two patients with carcinoma of the lung, factors, the age of the patient, the duration reported by Denny Brown in 1948, a group of of symptoms of carcinoma, and the blood Postgrad Med J: first published as 10.1136/pgmj.41.476.347 on 1 June 1965. Downloaded from June, 1965 PEARCE: The Non-Dystrophic Myopathies 353 group have been investigated, and found not producing weakness after repeated muscle to be related to the incidence of neuromyopathy contraction, commonly worse at the end of the in patients known to be suffering from breast day. Ag effort should be made to induce such or lung cancer (Croft and Wilkinson, 1963). weakness by repeatedly exercising the appro- The pathological changes are disproportion- priate muscles. ately slight compared to the extent of the The observed weakness is reversed within clinical signs. Minimal fibre atrophy with 2 minutes by intravenous edrophonium (10 mg. phagocytosis and nuclear chains, is all that diluted in 5 ml. saline), or within 30 minutes is usually seen. The nerve endings are quite by neostigmine 1.5 mg., i.m. Caution is needed different from those seen in myasthenia gravis. when using these tests in a treated but relapsed The commonest tumour implicated in the myo- patient, as a cholinergic crisis (neostigmine- pathic-myasthenic syndrome is a bronchogenic resistant) may be imminent. A curious differen- carcinoma. Carcinoma of breast, ovary, gastro- tial effect of neostigmine is not uncommon, in intestinal tract, kidney, and occasionally which ocular signs are reversed, but bulbar lymphomas, may produce an identical picture. muscles or limb muscles become weaker after The prognosis is from a few months to 2-3 the injection, or after oral medication. A late years, and treatment is directed at the primary sequel to myasthenia is a true myopathic growth. wasting and weakness which is not totally reversed by drugs. The Myasthenic Syndrome In an untreated patient, electromyography Myasthenia is an abnormal fatiguability of shows a characteristic decrement of evoked muscle. The commonest cause is myasthenia action potentials on repetitive supramaximal gravis, but as mentioned above, this symptom stimulation of the motor nerve (Simpson, 1960). may be secondary to thyrotoxicosis, and also The aetiology of this syndrome is still occurs in the myopathic-myasthenic syndrome unknown. There is a significant association associated with carcinoma. Myasthenia gravis with connective tissue disorders-especially by copyright. is dealt with elsewhere in this symposium, but rheumatoid arthritis, thyroid diseases, dissemi- some points of diagnostic importance are nated lupus erythematosus, and pernicious germane to this discussion. anaemia (Simpson, 1965). The response to The pathological changes in myasthenia thymectomy (Simpson, 1958) in some patients gravis are relatively sparse. They consist of is also suggestive of an auto-immune focal coagulative necrosis of one or many fibres, mechanism, since the role of the thymus in collections of lymphorrhages and simple fibre this group of diseases is certainly an important degeneration. These changes are not specific one, even though many details of the to myasthenia (Russell, 1953). Proliferation of mechanisms involved are still obscure. A http://pmj.bmj.com/ minute nerve fibres from the knobs of the thymoma is present in about 10% of patients terminal nerve fibres at the motor point, has who are usually difficult to control. been demonstrated in myasthenics, but the full significance of this finding is uncertain (Woolf, Conclusions 1963). These features are usually easy to In this account I have endeavoured to men- differentiate from the pathological picture seen tion the salient features of the more common in other and the technical details

myopathies. acquired myopathies, on September 26, 2021 by guest. Protected Myasthenia gravis may present at any age of research procedures have been deliberately from the neonatal period to late middle-life. omitted. The muscle appears to be a target It most frequently starts in the ocular muscles for many acquired systemic diseases, and it is producing ptosis and diplopia with normal only capable of reacting in certain ways pupillary size, The ocular muscles are involved governed by its intrinsic morphology and in 90% of patients, next in frequency are the function. Thus, both clinical signs and his- flexors and extensors of the neck, proximal tological, biochemical and electrophysiological muscles of the shoulder and pelvic girdles, and studies tend not to be specific for any one muscles of facial expression, chewing and disease. However a combination of all these swallowing, and phonation. Myasthenia may methods, and particularly the clinical back- remain localised to any one of the above groups ground, and the clinical evidence of other throughout the patient's life, or may spread systemic manifestations of the primary disease from one site to involve another after many will almost always allow the physician to make years. the correct diagnosis. This is particularly The cardinal feature is the fatiguability, rewarding in acquired myopathies, because Postgrad Med J: first published as 10.1136/pgmj.41.476.347 on 1 June 1965. Downloaded from 354 POSTGRADUATE MEDICAL JOURNAL June, 1965 amelio- KIRCHHEINER, B. (1962): Specific Muscle Lesions in specific therapy frequently produces Pituitary-thyroid Disorders, Acta med. scand., 172, ration of the patient's symptoms. 539. I am deeply indebted to Dr. John Walton, who MANCALL, E. L., and ROSALES, R. K. (1965): Necro- stimulated my interest in muscle diseases, and has so tizing Myelopathy associated with Visceral Car- freely given of his expert knowledge in this field. cinoma, Brain, 87, 639. MCARDLE, B. (1951): Myopathy due to a Defect in Muscle Glycogen Breakdown, Clin. Sci., 10, 13. REFERENCES MCARDLE, B. (1956): Familial Periodic Paralysis, ADAMS, R. D., DENNY-BROWN, D., and PEARSON, Brit. med. Bull., 12, 226. C. M. (1963): Diseases of Muscle. 2nd Ed. MCARDLE, B. (1962): Adynamia Episodica Heredi- London: Henry Kimpton. taria, Brain, 85, 121. ALESTIG, K., and BARR, J. (1963): Giant Cell Arteritis, MCARDLE, B. (1964): In Disorders of Voluntary Lancet, i, 1228. Muscle, ed. J. N. Walton, Chap. 15. London: BAGRATUNI, L. (1963): Prognosis in the Anarthritic J. & A. Churchill. Rheumatoid Syndrome, Brit. med. J., i, 513. MULLER, R., and KUGELBERG, E. (1959): Myopathy BARWICK, D. D., and WALTON, J. N. (1963): Poly- in Cushing's Syndrome, J. Neurol. Neurosurg. myositis, Amer. J. Med., 35, 646. Psychiat., 22, 314. BORMAN, J. B., DAVIDSON, J. T., and BLONDHEIM, PEARCE, J. M. S., PENNINGTON, R. J., and WALTON, S. H. (1963): Idiopathic Rhabdomyolysis, as an J. N. (1964): Serum Enzyme Studies in Muscle Acute Respiratory Problem, Brit. med. J., ii, 726. Disease. Part 2, ibid, 27, 96. BRAIN, W. R. (1963): The Neurological Complications PEARCE, J. M. S. (1965): Research in Muscular of Neoplasms, Lancet, i, 179. Dystrophy. 3rd Symposium. London: Pitman. CROFT, P. B., and WILKINSON, M. (1963): Carcino- PEARSON, C. M., and YAMAZAKI, J. N. (1958): matous Neuromyopathy, Lancet, i, 184. Vacuolar Myopathy in Systemic Lupus Erythp- CROMPTON, M. R., and MACDERMOT, V. (1961): matosus, Amer. J. clin. Path., 29, 455. Sarcoidosis Associated with Progressive Muscular PEARSON, C. M., RIMER, D. G., and MOMMAERTS, Wasting and Weakness, Brain, 84, 62. W. F. H. M. (1961): A Metabolic Myopathy due DENNY-BROWN, D. (1948): Primary Sensory Neuro- to Absence of Muscle Phosphorylase, Amer. J. pathy with Muscular Changes Associated with Med., 30, 502. Carcinoma, J. Neurol. Neurosurg. Psychiat., 11, PEARSON, C. M. (1964): In "Disorders of Voluntary 73. Muscle," ed. Walton, J. N., Chapter 12. London:by copyright. DRACHMAN, D. B. (1962): Myasthenia Gravis and the J. & A. Churchill. Thyroid Gland, New Engl. J. Med., 266, 330. POSKANZER, D. C., and KERR, D. N. S. (1961): A ENGEL, W. K., FOSTER, J. B., HUGHES, B. P., HUXLEY, Third Type of Periodic Paralysis with Normo- H. E., and MAHLER, R. (1961): Central Core kalaemia and Favourable Response to Sodium Disease, Brain, 84, 167. Chloride, Amer. J. Med., 31, 328. ENGEL, W. K., WANKO, T., and FENICHEL, G. M. (1964): Nemaline Myopathy, Arch.Neurol. (Chic.), RICHET, C., SOURDEL, M., and PERCOLA, A. (1937): 11, 22. Syndromes Parathyroidmusculaires, J. med. franc., GAMSTORP, I. (1956): Adynamia Episodica Heredi- 26, 377. taria, Acta. paediat. (Uppsala) Suppl., 108, 1. RUSSELL, D. S. (1953): Histological Changes in the GAMSTORP, I. A of Transient Muscular Striped Muscles in Myasthenia Gravis, J. Path.

(1962): Study http://pmj.bmj.com/ Weakness, Acta. psychiat. (Kbh), 38, 3. Bact., 65, 279. GAVRILESCU, K., and SMALL, J. M. (1962): Serum SATOYOSHI, E., MURAKAMI, K., KOWA, H., KINOSHITA, Electrophoretic Change in Polymyositis, Brit. med. M., NOGUCHI, K., HOSHINA, S., NISHIYAMA, Y., and J., 2, 1720. ITO, K. (1963): Myopathy in Thyrotoxicosis, GOLDING, D. N., MURRAY, S. M., PEARCE, G. W., and Neurology (Minneap.), 13, 645. THOMPSON, M. (1961): Corticosteroid Myopathy, SCHMID, R., and HAMMAKER, L. (1961): Hereditary Ann. phys. Med., 6, 171. Absence of Muscle Phosphorylase, New Engl. J. GORDON, I. (1960): Polymyalgia Rheumatica, Quart. Med., 264, 223. J. Med., 116, 473. SHY, G. M., and MAGEE, K. R. (1956): A New

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