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Polymyositis
Clinicopathologic Conference
Polymyositis rrNOLRArnm
reports, edited
by
Richard Aach,
M .D.
and John Kissane,
M .D.
Of
held in the Barnes and Wohl Hospitals, are S weekly clinicopathologictheconferences published in each issue Journal . These conferences are participated in jointly of
members of the Departments of Internal Medicine and Pathology of the Washington University School of Medicine and by Junior and Senior medical students . by
sixty-eight year old white woman was admitted to Barnes Hospital for the fourth time on September 8, 1964 . In February 1958 the patient was admitted to the orthopedic service of the Barnes Hospital for surgical repair of a trimalleolar fracture of the right ankle . Physical examination revealed no other abnormalities . Complete blood counts included a hemoglobin of 13 .5 gm . per cent and a white blood cell count of 8,900 per cu . mm . The differential revealed 63 per cent segmented neutrophils, 5 per cent stab forms, 5 per cent eosinophilic leukocytes, 9 per cent monocytes and 18 per cent lymphocytes . Blood sugar, nonprotein nitrogen, serum protein and protein-bound iodine levels were all normal, as was the electrocardiogram . An open reduction of the fracture was performed . Postoperative recovery was uneventful and the patient was discharged thirteen days later . In June 1962 the patient was readmitted to the Barnes Hospital because of progressive weakness in both lower extremities. One year prior to this admission, she began to note easy fatigability when trying to get up from a sitting position . Subsequently she had to use her hands to pull herself up from a chair, but she could walk unassisted . The patient complained of aching of her thigh muscles . A review of systems revealed that the patient had multiple allergies and was under the care of an allergist. Physical examination revealed a moderately obese, white woman in no distress . The blood pressure was 140/80 mm . Hg, and the pulse rate was 84 per minute and regular . Examination of the heart, lungs and abdomen revealed no abnormalities . Neurologic examination revealed an alert, well ori-
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ented person . The cranial nerves were intact . Examination of the motor system revealed weakness of the quadriceps and hamstring muscles bilaterally . The extrapyramidal and sensory tracts were intact . The reflexes were all physiologic . Pelvic examination disclosed no abnormalities . The hemoglobin was 13 .7 gm . per cent, white blood cell count 5,850 per cu . Lam . and the differential white blood cell count included 62 per cent segmented neutrophils, 10 per cent eosinophilic leukocytes, 26 per cent lymphocytes and 2 per cent monocytes . A urinalysis was normal and stool examination for occult blood was negative . Blood chemistry studies including fasting sugar, blood urea nitrogen, electrolytes, calcium, phosphorus, bilirubin, alkaline phosphatase, serum glutamic oxalic and pyruvate transaminases were all normal . Roentgenograms of the chest and skull were within normal limits, but films of the cervical and dorsolumbar spine showed degenerative arthritis . An electrocardiogram was normal. A lumbar puncture revealed normal fluid dynamics . The spinal fluid protein was 40 mg. per cent and the sugar 56 mg . per cent . No cells were seen with acid and the colloidal gold curve was negative . An electromyogram showed evidence of diffuse but scattered hyperirritability of muscle fibers . A neurology consultant diagnosed a primary myopathy and prescribed dexamethasone, 1 .5 mg., four times a day . Some improvement was noted and the patient was discharged thirty days after admission . Six months prior to the patient's third admission in September 1963, progressive, generalized weakness developed in the upper extremities bilaterally . The patient had also noted transient blurring of vision which was worse in the right eye . Two months prior to AMERICAN
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Polymyositis admission, the patient had weakness of the fingers and could not write legibly. Physical examination revealed a pleasant, obese white woman with a pulse rate of 70 per minute and regular, and a blood pressure of 120/80 mm . Hg . Ecchymoses were present over the forearms, legs and thighs . Ophthalmoscopic examination disclosed immature cataracts bilaterally . Examination of the chest, cardiovascular system and abdomen was unremarkable . Neurologic examination revealed an alert woman whose memory was intact . The cranial nerves were normal. There was wasting of the muscles of the hands bilaterally . Marked weakness of shoulder girdle and pelvic girdle muscles was noted. Fasciculations were not detectable . The extrapyramidal and sensory tracts were intact. The deep tendon reflexes were present and equal bilaterally . Bahinski reflexes were not present . Complete blood counts included a hemoglobin of 13 .3 gin . per cent, a hematocrit of 38 per cent and a total leukocyte count of 6,900 per cu . mm. The differential white blood cell count showed 56 per cent polymorphonuclear leukocytes, 37 per cent lymphocytes, 3 per cent monocytes and 4 per cent eosinophils . Red blood cell indices were normal as were urinalysis and stool examinations . The protein-bound iodine was 3 .4 µg. per cent and basal metabolic rates of -8 and -17 per cent were obtained . Roentgenograms of the chest were normal . Roentgenograms of the cervical, dorsal and lumbosacral spine revealed minimum progression of the osteoarthritic changes. Serum protein electrophoresis was normal . An electromyogram showed mild diffuse fibrillations suggestive of peripheral polyneuropathy . A lumbar puncture revealed normal fluid dynamics, normal glucose and protein levels, and no cells . The patient was treated with ACTH infusions for two weeks with some improvement . She was discharged one month after admission on a regimen of dexamethasone and t .-triiodothyronine tablets. The patient's final admission was in September 1964 . She had noticed progressive weakness for the preceding two months and was bedridden during the last two weeks . She admitted heavy alcohol intake during the preceding year, but denied excessive consumption in the past few months . Physical examination revealed a Cushingoid obese woman VOL .
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lying flat in bed . The pulse rate was 120 per minute and regular, respirations were 18 per minute, the blood pressure was 150/15 mm . Hg, and the temperature (oral) was 38 .3°c . Skin examination revealed multiple ecchymotic areas over the extremities . immature cataracts were present . Examination of the chest, heart and abdomen was unremarkable . Neurologic examination disclosed progression of wasting of muscle mass of both hands and increased weakness of the shoulder and pelvic girdle muscles . Reflexes were essentially unchanged except that the superficial abdominal reflexes were now absent bilaterally . Complete blood counts included a hemoglobin of 13 .9 gm . per cent and a total leukocyte count of 10,900 per cu. mm . The differential white blood cell count was 69 per cent polymorphonuclear leukocytes, 3 per cent band forms, 27 per cent lymphocytes and I per cent monocytes . Urinalysis failed to show any proteinuria or glycosuria, but microscopic examination revealed 3+ bacteria (gram-negative rods) and 6 to 20 white blood cells per high power field. Blood chemistry studies showed normal electrolytes, a blood urea nitrogen level of 7 .0 mg, per cent, serum glutamic oxalic and serum glutamic pyruvate transaminase levels of 18 and 14 units, respectively, a fasting blood glucose of 102 mg . per cent and creatinine 0 .75 mg. per cent . A lumbar puncture was entirely normal . Roentgenograms of the chest were unchanged except for a small, nodular soft tissue density in the left axilla . An electromyogram showed normal nerve conduction and some fibrillation . An electrocardiogram was normal . Urine culture yielded an abundant growth of Fscherichia coli. The patient was treated with oxytetracycline initially and then ampicillin, with a good response . She was given ACTH infusions daily in addition to prednisone, given orally . Thirty-three clays after admission the patient complained of diffuse abdominal pain . Tenderness was elicited in the epigastric area and the patient was treated with an antacid and an ulcer diet . Her pain intensified and roentgenograms of the abdomen revealed mechanical small bowel obstruction . A chest film showed a large hilar mass . Complete blood counts included a hemoglobin of 13 .3 gm. per cent and a total leukocyte count of 10,900 per cu . mm . The differen-
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tial count revealed 83 per cent segmented leukocytes, 5 per cent band forms, 9 per cent lymphocytes and 3 per cent monocytes . An exploratory laparotomy was performed . A volvulus of the upper jejunum was reduced and adhesions that were thought to be obstructing the jejunum were lysed . On the first postoperative day, the patient became hypotensive and the blood pressure was maintained by a levarterenol infusion . On the second postoperative day, she had difficulty in breathing and became unresponsive . Endotracheal suction yielded a large amount of yellow liquid . An electrocardiogram showed sinus tachycardia . Roentgenograms of the chest revealed a massive right pleural effusion . During the next three hours, the total urine output fell to less than 10 nil . and the patient died. CLINICAL DISCUSSION DR . EDWARD H . REINHARD : This white woman was sixty-one years old at the time of her first admission to Barnes Hospital in 1958 for a fractured right ankle . At that time she was apparently in good health except for the fracture . She first noted weakness of the lower extremities in June 1961 . Weakness progressed gradually until she was forced to pull herself up from a chair, although she could walk once she was on her feet . She also complained of aching in her thigh muscles . On her second admission to Barnes Hospital in line 1962 examination revealed no abnormalities except for weakness of the quadriceps and hamstring muscles bilaterally . An extensive laboratory work-up, including a lumbar puncture, was entirely negative except for a 10 per cent eosinophilia in the peripheral blood . Roentgenograms of the spine showed degenerative arthritis . An electroinyogranl revealed diffuse, scattered hyperirritability of muscle fibers . There seemed to be some improvement in the patient's condition following dexamethasone therapy . In March 1963 the patient noted generalized weakness in both upper extremities and transient blurring of vision . These symptoms became progressively more severe . In July 1963 she noted weakness of the fingers for the first time . On her third admission to Barnes Hospital in September 1963, there were extensive ecchymoses on the extremities and immature cataracts . The muscles of the hands were atrophied . There was marked weakness of the muscles of the
shoulder girdle and the pelvic girdle . Extensive laboratory tests were again normal, except for a protein-bound iodine level of 3 .4 pg. per cent . An electromyogram showed mild diffuse fibrillation . The patient was given an ACTII infusion for two weeks during which time there seemed to be some improvement . She was discharged from the hospital on a regimen of clexamethasone and triiodothyronine tablets. There was little change in her condition during the next ten months, but during the months of July and August 1964 her weakness progressed steadily and by late August she was completely bedfast. Her final admission to Barnes Hospital was in September 19694 at which time examination revealed a Cushingoid appearance, tachycardia and fever . There were multiple ecchymoses over the extremities . The blood pressure was 150/ 75 mm . Hg . There was further atrophy of the muscles of the hands and profound weakness of the muscles of the shoulder girdle and the pelvic girdle . The abdominal reflexes were absent bilaterally ; all other reflexes were normal . Blood counts were normal . Urinalysis revealed many bacteria and 6 to 20 white blood cells per high power field . Urine culture yielded a heavy growth of Esch. coli . Evidence of a urinary tract infection disappeared following ampicillin and later tetracycline therapy . The fasting blood sugar was 102 mg. percent . Spinal fluid was again normal on examination . The patient's many roentgenograms and electromyograms will be discussed subsequently . Histamine refractory achlorhydria was discovered at this time . Thirty-three days after the patient's admission to Barnes Hospital, diffuse abdominal pain developed and she died forty-eight hours later after an emergency abdominal operation . Let us first consider the major underlying disease from which this patient was suffering . Dr. Levy, would you discuss this patient's neurologic findings? DR . IRWIN LEVY : The patient's presenting complaint was weakness getting out of a chair . This would indicate muscle weakness of the pelvic girdle ; that is, a bilateral and proximal muscular abnormality . This particular pattern suggests an underlying muscle disorder rather than a neuropathy . It can be seen in either muscular dystrophy or in myositis . DR . REINHARD : Dr . Landau, electromyograms were obtained in this patient on three AMERICAN JOURNAL OF MEDICINE
Polymyositis different hospital admissions . The first two were interpreted as showing abnormalities more in keeping with a peripheral neuropathy than a myopathy . Would you discuss these records and tell us how you interpret them? DR . WILLIAM LANDAU : Abnormalities were present on each of the electromyograms . The most significant finding was the small, low voltage, I msec. potentials which occurred when the muscles under study were relaxed. These are defined as fibrillations and they represent hyperirritability in the muscle fibers . Another phenomenon observed in this patient was quite complex motor unit potentials indicating relatively poor synchronization and probably diminished populations of muscle fibers responding to anterior horn cell activity. In 1962 there were also some unusually large motor units, some which fired in doublets, and one locus of fasciculation . These are suggestive of a neuropathic process . Fibrillation indicates that something is definitely wrong with the muscle ; the muscle fihers are hyperirritable . The most common condition leading to fibrillation is denervation of the muscle . But the same kind of hyperirritability can be due to primary muscle disease and there are three quite reasonable pathogenetic mechanisms by which this may take place . First, an inflammatory process damaging the metabolism of muscle membrane could produce hyperirritability directly . Consider that a muscle fiber is quite long and usually has more than one end-plate which connects to one parent axon . A second mechanism confirmed by histopathologic studies is focal necrosis in a muscle fiber which disconnects a segment from end-plate regions . Thus, that segment is, in effect, denervated even though its motor neuron survives . Studies' have shown what happens to the main part of the muscle fiber when it is deprived of end-plate innen-ation . The excitability of the membrane increases greatly. Whereas the normal muscle fiber away from the end-plate is relatively insensitive to acetyl choline and mechanical stimulation, following a period of divorce from the end-plate region, it becomes hyperexcitable . The same physiologic changes in the main muscle fiber have been produced by chronic poisoning with a pharmacologic 1 THESLRFF, S . Effects of motor innervation on the chemical sensitivity of skeletal muscle . Physiot. Rev., 40 : 734, 1960 .
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end-plate blocking agent, botulinus toxin . These effects probably involve something more than a loss of the intermittent traffic of action potentials at the end-plate . In any case, one can produce electromyographic changes of denervation without anatomic denervation . Finally, there is pathologic evidence that inflammatory process in muscle may involve intramuscular nerve branches themselves in a focal inflammatory neuritis . The motor unit changes that were seen in this patient can be encountered in either myopathic or neuropathic processes related to the chronic patterns of loss of muscle fibers in the motor unit population . This may happen when single fibers fall out in a myopathy and may persist when new nerve branches grow out to muscle fibers that have been damaged or orphaned by the diffuse pathologic process. In the course of destruction of single muscle fibers, fewer join in the population of the discharging motor unit ; thus, a low voltage polyphasic discharge associated with effort is commonly observed and is called a myopathic motor unit . If the motor unit pattern is prolonged, or of particularly high voltage, the finding sug gests that nerve disconnection may have been followed by re-innervation . Such units are typical in chronic and partially recovering neuropathic disturbances and some were observed in 1964 . Re-innervation units may be large if a parent axon branches widely . These are commonly observed in motor neuron disease in which there is a decimation of the anterior horn cell population and surviving motor neurons put out collateral nerve branches within the muscle to pick up the orphaned muscle fibers . Thus, the surviving motor unit is larger than normal . In summary, the most convincing evidence indicates that this patient had a chronic irritative condition involving muscle . The finding of fibrillation per se does not distinguish between denervation and a primary myopathic process . The only direct test we have of peripheral nerve function, the conduction time, was normal in this patient . But normal conduction time does not exclude a neuropathic process and motor unit findings suggestive of neuropathy were observed . DR- REINHARD : Dr . Berg, you saw this patient during her second and third hospital admissions . If I read your notes correctly, you
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believed this patient had a polymyositis rather than a polyneuritis . Would you tell us why you came to this conclusion? DR . LEONARD BERG : On clinical examination there was never really anything to suggest that either the peripheral nerves or the anterior horn cells were involved. In addition to the fact that a pattern of proximal weakness was always present, the tendon reflexes remained normal ; there were never fasciculations, sensory changes or spread to the bulbar musculature . Throughout the patient's course, the clinical picture was always that of a primary myopathy and not that of nervous system disease . DR . REINHARD : Dr. Weiss, do you have anything to add to Dr. Berg's comments? Do you think that this is a polymyositis? DR. STUART WEISS : The weight of evidence is in favor of a myopathy . I would agree with Dr. Berg . DR. REINHARD : Dr . Klinkerfuss, we do not have any direct evidence that this patient had a malignant tumor, but various neuropathies and myopathies occur in association with tumors . Would you describe the neuromuscular disorders that may result from metabolic alterations caused by cancer, excluding direct nerve or muscle involvement by cancer? DR . GEORGE KLINKERFUSS : There are several central nervous system complications of distant malignancy which I will not discuss at this time. When the peripheral nervous system and muscle are considered, about four entities have been separated on clinical grounds and attributed to nonmetastatic complications of malignancy. In a given patient, these entities may be manifest in any number of combinations . Probably the most rare, and therefore the most likely to be discussed first, is the Eaton-Lambert syndrome . This is a defect primarily in neuromuscular transmission . Secondly, a pure sensory neuropathy is described and fairly well accepted . Thirdly, there is a motor neuropathy or anterior horn cell disease which is associated with carcinoma, and finally, there is a primary muscle manifestation called polymyositis, dermatomyositis, etc . This can be extremely low grade or rather fulminant . It can occur in a person years before the primary cancer is manifest on investigation . These would be the main points for consideration in association with carcinoma . DR. REINHARD : Do you think that the pattern in this patient was a type seen fairly often
in association with cancer? Would a polymyositis be one of the more common ones? DR . KLINKERFUSS : Yes, polymyositis is well documented to be the most common pattern seen with carcinoma and the patient's findings would fit this clinical pattern . DR. REINHARD : Dr. Perkoff, our neurologic colleagues seem to think that this patient had a disorder that is primary and that affected the muscles, not the nervous system . Are you willing to accept this as a myositis? DR. GERALD PERKOFF : The features this patient showed are quite compatible with the diagnosis of polymyositis, but without any biopsy information it is difficult to be sure the term "myositis" means inflammation . Frequently when we make the diagnosis of "polymyositis," what we are dealing with is progressive proximal weakness of relatively late onset and on biopsy we are often very disappointed. We do not know what else to call it, so we call it polymyositis . DR. REINHARD : It is surprising that a biopsy was not performed in this patient . It might have been of great help, might it not? DR. PERKOFF : Frankly, I just assumed the information was available but that it was left out of the protocol . It is worth noting that some distal muscular weakness subsequently developed. The patient became unable to write, her hands were clumsy, and it is entirely possible that she had a peripheral neuropathy . We may be dealing with two muscle diseases . First, there was the underlying disorder which brought the patient to the hospital and which might be called a primary myopathy, or neuromyopathy. Then she was treated extensively with steroids over a long period of time and recognizable features of Cushing's syndrome developed. We know that both in spontaneous Cushing's disease and in that induced by exogenous steroids, a proximal myopathy may occur, Frequently it is difficult to know whether the underlying myopathy being treated with steroids has become more acute or whether a second disorder has been added as a result of steroid therapy . DR. REINHARD : What about the possibility of a third type of myopathy? This patient was a rather heavy drinker which raises the possibility of an alcoholic myopathy . DR. PERKOFF : If one approaches this kind of problem from the standpoint of late onset of proximal muscle weakness, then one need not AMERICAN JOURNAL OF MEDICINE
Polymyositis call this polymyositis per se . It could have been a neuropathy associated with cancer. It could also have been a chronic myopathy and neuropathy associated with alcoholism . If she had been a heavy drinker and had continued drinking throughout her course, there is nothing in her history incompatible with that diagnosis . However, as we have stated here before, in the absence of more certain history, and without elevated enzyme levels and/or a biopsy, we cannot make that diagnosis . If this patient had been a man with symmetrical proximal weakness beginning after the age of fifty, according to some studies we would have as much as a 70 per cent chance of harboring a malignancy . 2 In women beyond the age of fifty with acquired proximal muscle weakness, the incidence of cancer still is about 25 per cent . The possibility of an association with tumor then, remains a real one at this point . DR . REINHARD : Dr . Perkoff, could you tell us something about the incidence of polymyositis and myopathies in association with various types of cancer . Is there any particular type in which this is most common? DR . PERKOFF : Most of the cases have been reported with three kinds of cancer : carcinoma of the lung, particularly in men ; carcinoma of the ovary and carcinoma of the breast . Of these, there is always concern that the high incidence in these tumors is only a manifestation of the frequency of the tumors ; this would be particularly so with cancer of the lung and breast. But in carcinoma of the ovary, there seems to be some discrepancy between the incidence of the tumor itself and the incidence of associated myopathy . However, almost every kind of tumor has been recognized as associated with this kind of process, so there is no known specificity about the histology of the tumor . DR . REINHARD : We are all delighted to have Dr. Irving London with us here this week as visiting professor. Dr. London, a slight eosinophilia was found on several occasions . Ten per cent eosinophils and 4 and 5 per cent eosinophils were recorded on differential counts of the peripheral smear during separate hospital admissions, Several differential counts showed no eosinophils at all . Is this mild and intermittent eosinophilia pertinent to any one of the ' SHY, G. M . and SILVERSTEIN, 1 . A study of the effects upon the motor unit by remote malignancy. Brain, 88 : 515, 1965 . VOL . 46, FEBRUARY 1969
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diagnoses we have been discussing? Do you think this patient might have dermatomyositis without a skin rash? DR . IRVING LONDON : This patient has a history of allergy of a rather indeterminate nature . The eosinophilia could have been associated with an allergic state or it could have been associated with an underlying neoplastic p rocess . i t is not clear why the eosinophils disappeared completely unless this was due to the steroid therapy . In a word, the eosinophilia is difficult to interpret but is compatible with an underlying neoplastic disorder . DR . REINHARD : I am very glad you brought out this point . I think this needs emphasis . We do not ordinarily think of eosinophilia as being a manifestation of cancer, but there are reports in the literature 3 of patients who have had eosinophil counts even up to 50, 60 or 70 per cent, in which the cause was apparently a tumor. In my own experience, this has usually been quite a large tumor, not an occult tumor, however. I would like to quote from an article on dermatomyositis by A . McGehee Harvey,4 "The clinical features of dermatomyositis are variable both in their intensity from case to case and in the pattern of onset which may be gradual or abrupt . At one end of the spectrum are the acute cases with fever, generalized muscle tenderness, weakness, edema and the characteristic heliotrope skin eruption . At the opposite extreme are the cases of chronic polymyositis, usually in older patients, who slowly develop weakness of the girdle and proximal limb muscles and who have minimal or no skin involvement and no constitutional signs ." Certainly this end of the spectrum fits in perfectly with our patient today. Dr . Perkoff, is there any difference between dermatomyositis and polymyositis, or are these different clinical manifestations of the same disease process? DR . PERKOFF : The answer to that question is not known . There are other grades in between straightforward dermatomyositis and polymyositis. Patients may have a lupus-like disease or have lupus with myositis ; some have features of rheumatoid disease . In others, the • TsAAcsoN, N . H. and RAPOPORT, P . Eosinophilia in malignant tumors . Ann . Int . Med., 25 : 893, 1946 . • HARVEY, A . MEG. In : Section on Diseases of Connective Tissue. Cecil-Loeb Textbook of Medicine, p. 456. Edited by Beeson, P . and McDermott, W . Philadelphia, 1967 . W . B . Saunders Co .
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lupus or rheumatoid features predominate . Polymyositis may be very acute, just like dermatomyositis, but without a skin rash . I do not really believe it is possible to make much out of the fact that there is or is not a skin rash in patients with inflammatory muscle disease . The muscle disease may look exactly the same. From a pathogenetic point of view, when people have looked for evidence of immune abnormalities in patients with polymyositis, it has not been very easy to find them . Specific antimuscle antibodies cannot be detected regularly in the serum of such patients . On the other hand, some such patients have accelerated turnover of immunoglobulin . Dr . R. Dean Wochner at St . Louis City Hospital is studying some of these patients now, but it really is not possible to decide whether or not the two syndromes are the same or different on the basis of the information presently available. DR . REINHARD : Now we come to a consideration of the catastrophic events of the last fortyeight hours of this patient's life . Thirty-three days after the patient was admitted to Barnes Hospital for the fourth and last time, she had severe abdominal pain . It was most severe in the epigastrium and perhaps in the lower substernal area . There was marked tenderness in the epigastrium . An ulcer diet was instituted and the patient was given antacids . The next day an exploratory laparotomy showed evidence of an acute abdomen, and she died forty-eight hours after the onset of the pain . Dr . Torrance, would you please discuss the patient's roentgenograms? DR . DANIEL TORRANCE : A plain film of the abdomen taken at the time when the patient was having the abdominal pain showed markedly dilated loops of small bowel . The location is that of dilated jejunum and there was increased space between parallel loops indicating thickening of the bowel wall . These findings are consistent with proximal small intestinal obstruction . I would like to flash back in time and review the patient's many chest films . Those taken in 1962 and in 1963 were perfectly normal . There was a subtle change in the mediastinum on the chest films taken in 1964 during her last hospital admission . Further, there was a more obvious change in the lung fields . Late in her final hospitalization, a very bizarre looking central density developed in the right mid-lung field and a peri-
hilar density which obliterated the vascular outline of the hilar shadows . The lesion in the right lung increased very rapidly during a one day period and within two days there was evidence that something catastrophic had developed with a massive right pleural effusion and rather striking mediastinal widening behind the aortic arch . This suggests that an acute hemorrhage may have occurred and that perhaps it was related to the patient's abdominal catastrophe . DR . REINHARD : Dr . Peterson, at laparotomy a volvulus was found . This involved the upper part of the jejunum . The involved bowel was 18 inches in length ; it was pink . The volvulus was reduced and unwound, and the jejunum was dropped back into place . Nothing was resected . Would you tell us what some of the causes of volvulus are and would you comment specifically on volvulus of the upper part of the jejunum . I understand this is rather rare, is it not? DR . MALCOLM PETERSON : It is rare . Dr. Reinhard, I cannot think of anything that would be suggestive of a predisposing factor for development of this patient's volvulus . She was obese ; volvulus is sometimes associated with emaciation . The speculation is that the weight loss and changes in fat around the bowel and mesentery allow pendulous portions of the bowel to rotate on the mesentery . The possibility of an internal hernia is always certainly present, but I think it would have been described at surgery. So all I can say is that this is indeed one of the rarest portions of the bowel to be involved by volvulus ; factors which might predispose to it, including congenital malrotation and internal hernia, were not present . Interestingly enough, for some reason volvulus of the intestine is generally seen more commonly in men than in women . There is the possibility that there could be a tumor in the intestine . Since the possibility of an occult neoplasm is a real one, I pursued this to the extent of looking at several monographs . I can find no reference to this being a likely cause for volvulus . DR . REINHARD : If there were a tumor we presume that it would have been found by the surgeon, unless it was very small . Dr . London, this patient had achlorhydria, even after intensive histamine stimulation . A Schilling test showed only 4 .3 per cent urinary excretion of AMERICAN JOURNAL OF MEDICINE
Polymyositis the tagged vitamin B 12 . However, at no time did the patient have anemia ; the red blood cell indices were perfectly normal, and no hypersegmentation of the polymorphonuclear leukocytes was ever noted . It seems clear that the patient did not have pernicious anemia . It is noteworthy that the Schilling test was performed just six days before the patient had severe abdominal pain which was shown on laparotomy to be due to this volvulus . I wonder if you will tell us where vitamin B 12 is absorbed in the gastrointestinal tract, where you think the releasing factor comes from, and whether it is possible that the patient had a disturbance of the gastrointestinal tract six days prior to the development of the acute volvulus that might have interfered with vitamin B12 binding, vitamin B, 2 release from its binding to intrinsic factor, or subsequent absorption into the blood stream? DR . LONDON : The physiologic absorption of vitamin B 12 requires prior binding to intrinsic factor and the vitamin B 12-intrinsic factor complex travels from the stomach and upper small intestine to the lower ileum where vitamin B 32 is largely absorbed. The orientation of intrinsic factor-vitamin B 12 complex toward the mucosa of the ileum also requires inorganic calcium . You raised the question of the mechanism of releasing vitamin B 12 from the intrinsic factor complex . Very little is known about it but I would guess that the release action occurs in the mucosa of the ileum . Your question of whether the low values on the Schilling test were related to a disturbance in the gastrointestinal tract prior to the development of a volvulus is reasonable . Although the patient did not present symptoms suggestive of a chronic gastrointestinal disturbance, she did have achlorhydria and some diminution in intrinsic factor may have developed . The absence of evidence of pernicious anemia does not rule out a diminution of intrinsic factor because if she had had normal stores of vitamin B 12 , it could require as much as two to three years to deplete these stores. It is reasonable therefore to raise the question of a more chronic gastrointestinal disturbance . DR . REINHARD : Of course, the other possibility is that some of the urine was lost and the results of the test therefore were not valid . The day after laparotomy the patient was hypotensive . The following day she began to VOL .
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have difficulty in breathing . She became unresponsive . Endotracheal suction yielded a large amount of yellow fluid . The striking changes described by Dr . Torrance were seen on the chest films . Dr. Roper, what was happening during these last forty-eight hours to cause this remarkable change in the appearance of the right side of the chest? DR. CHARLES ROPER : Although this patient's history is quite compatible with occult carcinoma of the lung, there is no evidence to support this diagnosis . Fever and an infiltrate in the lung suggest the development of a pneumonitis and the most likely etiology of the abnormalities of her last chest films was a severe aspiration pneumonitis, which occurred either in the immediate postoperative period or during the time of surgery. Both an underlying pneumonia and an episode of aspiration can give rise to a massive effusion . She had very little atelectasis ; this was predominantly effusion . DR . REINHARD : Dr. Smith, what do you think of the possibility that this was a vascular accident, a ruptured aneurysm, for example? DR . JOHN R. SmiTH : On the basis of the information Dr . Torrance has given us and the terminal x-ray picture of a marked widening of the mediastinum above the heart, I wonder whether or not there may have been aortic disruption with bleeding into the mediastinum and into the pleural space- This, of course, is conjectural . Ordinarily, this event is accompanied by considerable pain, which did not occur here . However, this is a distinct possibility and I would personally favor this diagnosis . An interesting aspect of this disease is that, if indeed it is a dissecting aneurysm, this patient also had mild hypothyroidism managed by exogenous thyroid. It was noted years ago that hypothroidism is associated with medial cystic necrosis of the aorta, particularly when this is complicated by hypertension . This patient did not seem to have hypertension, therefore the argument for this disease is considerably weakened . On the other hand, there is no evidence of overt atherosclerosis of the aorta. The patient did not seem to have syphilis, but the possibility remains that the aorta may have eroded, if one wants to argue that this was deterioration of the aorta . DR. REINHARD : We will have to terminate our discussion now. I therefore present as our
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final diagnoses a primary myopathy, possibly complicated by steroid therapy, possibly aggravated by alcohol . We are concerned about the possibility that the patient might have had an occult tumor and that this was a cause of the myopathy. The patient certainly had iatrogenic Cushing's syndrome, and I agree with Dr . Smith that the terminal event was probably a rupture of an aortic aneurysm of the chest . I cannot account for the sudden appearance of pleural fluid on the basis of an aspiration pneumonia nor can I fit the volvulus in with the other events at all, and I believe it was a purely coincidental event at a very inopportune time . PATHOLOGIC DISCUSSION
DR . JOHN KISSANE : This case presented very interesting anatomic findings : some are purely objective, some are the basis for what we believe is a well documented interpretation, and others remain the subject perhaps for speculation . We do have the cause of death . The entire middle lobe and the apical portion of the lower lobe of the right lung were consolidated, both grossly and microscopically. We would have to call this lobar pneumonia . Gram stains showed lancet-shaped diplococci, and histologically the lesion was typical of pneumococcal lobar pneumonia . Succulent nodes were described presenting into the right pleural cavity. The aorta was normal . No tumor was found . Peripheral nerves and muscles were examined in considerable detail . We have to say that all accessible nerves were normal . There was no inflammation, no fibrosis and
Fm. 1 . Larvae of T . spiralis in jejunal submucosa . Hematoxylin and eosin stain, original magnification X 120 .
no demyelination. Skeletal muscle, itself, was not histologically normal . The abnormalities were somewhat subtle and consist of a variation in fiber size and general diminution of fiber size, more or less randomly distributed through the skeletal muscles, not in a fascicular or motor unit pattern which we would recognize as neurogenic atrophy . There was, in addition, some increase in sarcolemmal nuclei which gave an impression of cellularity to the skeletal muscle. There was no bona fide interstitial inflammatory reaction, no necrosis and no acute component to this rather nonspecific patchy atrophy of the muscle . Now let me direct your attention to the previously volvulated segment of the jejunum . We saw a somewhat inflammed submucosa and, in addition, forms (Fig. 1) in the crypts of the intestinal glands . These are the transverse sections of worms which microscopically can be identified as Trichinella spiralis . This infestation was particularly heavy in the mid-jejunum . Every section showed, in every high power field, really dozens of larvae of Trichinella . Available sections of skeletal muscle showed (Fig . 2) transverse sections of larval Trichineae in the interstium of a few of the skeletal muscles . These were not encysted ; they were not in the muscle fibers themselves but free in the interstium, presumable in transit from the vasculature within the skeletal muscle bundle . This patient then had trichinosis in the intestinal stage at the time of her death . I think it is highly probable that disturbed intestinal motility resulting from the extremely heavy intestinal infestation led to the volvulus . It was James Paget, otherwise notable, who as a young medical student first established that the calcified granules occasionally observed in human skeletal muscle were endoparasites . The name Trichina spiralis (later changed to Trichinella spiralis) was applied to the worm by one Robert Owen, later to become famous for his discovery of the parathyroid glands during a dissection of an Indian rhinoceros. One of the earliest students, and certainly the most illustrious, of experimental trichinosis was Rudolph Virchow. The very stringent federally regulated inspection of pork carcasses in force in Germany (and by imitation, elsewhere in western Europe) toward AMERICAN JOURNAL OF MEDICINE
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Polymyositis the end of the last century was, however, as much a product of Virchow's role as the foremost liberal politician of his day as it was a tribute to his standing as a scientist . There were, in Germany in 1895, some 25,000 federal functionaries engaged in the inspection of pork products, a figure very nearly equal to the strength of the standing army of the United States in that same year .' There are some curious and provocative facets to the epidemiology of trichinosis. Many investigators have remarked upon the tendency of trichinosis to occur in ministers and in teachers, pursuers of historically mendicant professions traditionally dependent upon dinner invitations to eke out their mite . Less well known is the tendency for trichinosis to afflict physicians, who ought to know better . In one outbreak in California, three of twentyone persons afflicted were physicians . With regard to the biology of Trichinella spiralis, we can reiterate that the parasite pursues its life cycle in a single definitive host . More importantly for our purposes in interpreting this case is the fact that trichinosis, unlike many endoparasitoses, is a relatively acute disease, the several stages of which have been experimentally fairly narrowly delimited chronologically . Release of encysted larvae from ingested food occurs in the duodenum and upper part of the jejunum within hours, and liberated larvae promptly mature, If both sexes are present, copulation occurs, maturation and mating of adult worms requiring about five days . The female Trichinella is ovoviviparous, that is, delivers alive from her vagina, larvae which have hatched in utero . A single gravid worm delivers 1,000 to 1,500 larvae at a rate of one per half hour over many weeks . Larvae reach the circulating blood via intestinal lacteals and are carried to skeletal muscle where they leave the vasculature, coil and encyst, processes requiring about seventeen days . The point of the recitation is that the sequence in the evolution of trichinosis, dated from ingestion of infested meat, occupies only weeks . One episode of intestinal and extravascular muscular trichinosis cannot, therefore, explain our patient's long history of neuromuscular disturbance . Detailed review of available microsections of GOULD, S . E ., Trichinosis . Springfield, Ill ., 1945 . Charles C Thomas . VOL .
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FIG . 2 . Larvae of T . spiralis in interstitium of skeletal muscle . Hematoxylin and eosin stain, original magnification 280 .
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skeletal muscle did, at length, however reveal old, indeterminately old, calcified cysts of Trichinella larvae in one section (Fig . 8) . Our patient, therefore, died of lobar pneumonia after sustaining a mid-gut volvulus in the course of intestinal trichinosis. She had had trichinosis, evidenced by old intramuscular cysts, at least once before . We have no other morphologic explanation for the patient's previous impairment of neuromuscular function . DR . REINHARD : Dr. Perkoff, do you have any comment on the polymyositis or the myopathies? Do you think this really could be due to the trichinosis? DR. PFRKOFr : I do not really see how we can say whether or not this resulted from old trichinosis . Certainly there are cases on record in which polymyositis supposedly resulted from trichinosis, but usually many more cysts are found in the muscle. This patient did have eosinophilia throughout the entire ten years she was seen here .
FIG . .1 . Empty cyst in skeletal muscle. Hematoxylin and eosin stain, original magnification x 200 .
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DR . REINHARD : Ten per cent only once. On all other occasions the eosinophil counts were within normal limits . DR . PERKOFF : Apparently the eosinophilia in trichinosis is variable . In at least one-fourth of the patients with trichinosis there is never any eosinophilia at all, and when present it may be intermittent, so I would not say that this could not be trichinosis . We did not see any vacuoles like those found frequently in steroid myopathy. DR . KISSANE : There were no features of any specific myopathy. DR . REINHARD : Dr. Levy and Dr. Berg, this was your patient. You knew what the autopsy showed and perhaps you have had longer to think about this than the rest of us . Do you think that trichinosis could account for this patient's myopathy? DR . LEVY : I would say that the clinical course was certainly different from that which is clinically typical of trichinosis . DR . REINHARD : I would agree with that! DR . LEVY : There were clinical representations of an acute phase. Ordinarily it occurs
with the invasion of muscle . Certainly none of the ordinary findings ever occurred in this person's history . I think there is some reason to doubt that trichinosis contributed to the myopathy. DR. REINHARD : Dr . Kissane, did you look up in the literature and evaluate cases similar to this attributed to trichinosis? DR . KtssANE : I did not find similar descriptions in die literature, but muscles certainly may become atrophic . Trichinosis is an acute disease and ordinarily self-limited. However, she certainly had had trichinella infestation at least once, and perhaps more than once . Pathologic diagnoses were widespread but slight atrophy of skeletal muscle fibers not typical of neurogenic atrophy (history of clinical diagnosis of polyneuropathy treated with steroids and ACTH) ; empty cyst of T. spiralis in deltoid muscle ; larvae of Trichinella spiralis in the jejunum and in skeletal muscle ; recent abdominal incision (reduction of volvulus one day before death) ; lobar pneumonia, middle and lower lobes of right lung ; pleural effusion (800 ml .) .
AMERICAN JOURNAL OP MEDICINE
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reports, edited
by
Richard Aach,
M .D.
and John Kissane,
M .D.
Of
held in the Barnes and Wohl Hospitals, are S weekly clinicopathologictheconferences published in each issue Journal . These conferences are participated in jointly of
members of the Departments of Internal Medicine and Pathology of the Washington University School of Medicine and by Junior and Senior medical students . by
sixty-eight year old white woman was admitted to Barnes Hospital for the fourth time on September 8, 1964 . In February 1958 the patient was admitted to the orthopedic service of the Barnes Hospital for surgical repair of a trimalleolar fracture of the right ankle . Physical examination revealed no other abnormalities . Complete blood counts included a hemoglobin of 13 .5 gm . per cent and a white blood cell count of 8,900 per cu . mm . The differential revealed 63 per cent segmented neutrophils, 5 per cent stab forms, 5 per cent eosinophilic leukocytes, 9 per cent monocytes and 18 per cent lymphocytes . Blood sugar, nonprotein nitrogen, serum protein and protein-bound iodine levels were all normal, as was the electrocardiogram . An open reduction of the fracture was performed . Postoperative recovery was uneventful and the patient was discharged thirteen days later . In June 1962 the patient was readmitted to the Barnes Hospital because of progressive weakness in both lower extremities. One year prior to this admission, she began to note easy fatigability when trying to get up from a sitting position . Subsequently she had to use her hands to pull herself up from a chair, but she could walk unassisted . The patient complained of aching of her thigh muscles . A review of systems revealed that the patient had multiple allergies and was under the care of an allergist. Physical examination revealed a moderately obese, white woman in no distress . The blood pressure was 140/80 mm . Hg, and the pulse rate was 84 per minute and regular . Examination of the heart, lungs and abdomen revealed no abnormalities . Neurologic examination revealed an alert, well ori-
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ented person . The cranial nerves were intact . Examination of the motor system revealed weakness of the quadriceps and hamstring muscles bilaterally . The extrapyramidal and sensory tracts were intact . The reflexes were all physiologic . Pelvic examination disclosed no abnormalities . The hemoglobin was 13 .7 gm . per cent, white blood cell count 5,850 per cu . Lam . and the differential white blood cell count included 62 per cent segmented neutrophils, 10 per cent eosinophilic leukocytes, 26 per cent lymphocytes and 2 per cent monocytes . A urinalysis was normal and stool examination for occult blood was negative . Blood chemistry studies including fasting sugar, blood urea nitrogen, electrolytes, calcium, phosphorus, bilirubin, alkaline phosphatase, serum glutamic oxalic and pyruvate transaminases were all normal . Roentgenograms of the chest and skull were within normal limits, but films of the cervical and dorsolumbar spine showed degenerative arthritis . An electrocardiogram was normal. A lumbar puncture revealed normal fluid dynamics . The spinal fluid protein was 40 mg. per cent and the sugar 56 mg . per cent . No cells were seen with acid and the colloidal gold curve was negative . An electromyogram showed evidence of diffuse but scattered hyperirritability of muscle fibers . A neurology consultant diagnosed a primary myopathy and prescribed dexamethasone, 1 .5 mg., four times a day . Some improvement was noted and the patient was discharged thirty days after admission . Six months prior to the patient's third admission in September 1963, progressive, generalized weakness developed in the upper extremities bilaterally . The patient had also noted transient blurring of vision which was worse in the right eye . Two months prior to AMERICAN
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Polymyositis admission, the patient had weakness of the fingers and could not write legibly. Physical examination revealed a pleasant, obese white woman with a pulse rate of 70 per minute and regular, and a blood pressure of 120/80 mm . Hg . Ecchymoses were present over the forearms, legs and thighs . Ophthalmoscopic examination disclosed immature cataracts bilaterally . Examination of the chest, cardiovascular system and abdomen was unremarkable . Neurologic examination revealed an alert woman whose memory was intact . The cranial nerves were normal. There was wasting of the muscles of the hands bilaterally . Marked weakness of shoulder girdle and pelvic girdle muscles was noted. Fasciculations were not detectable . The extrapyramidal and sensory tracts were intact. The deep tendon reflexes were present and equal bilaterally . Bahinski reflexes were not present . Complete blood counts included a hemoglobin of 13 .3 gin . per cent, a hematocrit of 38 per cent and a total leukocyte count of 6,900 per cu . mm. The differential white blood cell count showed 56 per cent polymorphonuclear leukocytes, 37 per cent lymphocytes, 3 per cent monocytes and 4 per cent eosinophils . Red blood cell indices were normal as were urinalysis and stool examinations . The protein-bound iodine was 3 .4 µg. per cent and basal metabolic rates of -8 and -17 per cent were obtained . Roentgenograms of the chest were normal . Roentgenograms of the cervical, dorsal and lumbosacral spine revealed minimum progression of the osteoarthritic changes. Serum protein electrophoresis was normal . An electromyogram showed mild diffuse fibrillations suggestive of peripheral polyneuropathy . A lumbar puncture revealed normal fluid dynamics, normal glucose and protein levels, and no cells . The patient was treated with ACTH infusions for two weeks with some improvement . She was discharged one month after admission on a regimen of dexamethasone and t .-triiodothyronine tablets. The patient's final admission was in September 1964 . She had noticed progressive weakness for the preceding two months and was bedridden during the last two weeks . She admitted heavy alcohol intake during the preceding year, but denied excessive consumption in the past few months . Physical examination revealed a Cushingoid obese woman VOL .
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lying flat in bed . The pulse rate was 120 per minute and regular, respirations were 18 per minute, the blood pressure was 150/15 mm . Hg, and the temperature (oral) was 38 .3°c . Skin examination revealed multiple ecchymotic areas over the extremities . immature cataracts were present . Examination of the chest, heart and abdomen was unremarkable . Neurologic examination disclosed progression of wasting of muscle mass of both hands and increased weakness of the shoulder and pelvic girdle muscles . Reflexes were essentially unchanged except that the superficial abdominal reflexes were now absent bilaterally . Complete blood counts included a hemoglobin of 13 .9 gm . per cent and a total leukocyte count of 10,900 per cu. mm . The differential white blood cell count was 69 per cent polymorphonuclear leukocytes, 3 per cent band forms, 27 per cent lymphocytes and I per cent monocytes . Urinalysis failed to show any proteinuria or glycosuria, but microscopic examination revealed 3+ bacteria (gram-negative rods) and 6 to 20 white blood cells per high power field. Blood chemistry studies showed normal electrolytes, a blood urea nitrogen level of 7 .0 mg, per cent, serum glutamic oxalic and serum glutamic pyruvate transaminase levels of 18 and 14 units, respectively, a fasting blood glucose of 102 mg . per cent and creatinine 0 .75 mg. per cent . A lumbar puncture was entirely normal . Roentgenograms of the chest were unchanged except for a small, nodular soft tissue density in the left axilla . An electromyogram showed normal nerve conduction and some fibrillation . An electrocardiogram was normal . Urine culture yielded an abundant growth of Fscherichia coli. The patient was treated with oxytetracycline initially and then ampicillin, with a good response . She was given ACTH infusions daily in addition to prednisone, given orally . Thirty-three clays after admission the patient complained of diffuse abdominal pain . Tenderness was elicited in the epigastric area and the patient was treated with an antacid and an ulcer diet . Her pain intensified and roentgenograms of the abdomen revealed mechanical small bowel obstruction . A chest film showed a large hilar mass . Complete blood counts included a hemoglobin of 13 .3 gm. per cent and a total leukocyte count of 10,900 per cu . mm . The differen-
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tial count revealed 83 per cent segmented leukocytes, 5 per cent band forms, 9 per cent lymphocytes and 3 per cent monocytes . An exploratory laparotomy was performed . A volvulus of the upper jejunum was reduced and adhesions that were thought to be obstructing the jejunum were lysed . On the first postoperative day, the patient became hypotensive and the blood pressure was maintained by a levarterenol infusion . On the second postoperative day, she had difficulty in breathing and became unresponsive . Endotracheal suction yielded a large amount of yellow liquid . An electrocardiogram showed sinus tachycardia . Roentgenograms of the chest revealed a massive right pleural effusion . During the next three hours, the total urine output fell to less than 10 nil . and the patient died. CLINICAL DISCUSSION DR . EDWARD H . REINHARD : This white woman was sixty-one years old at the time of her first admission to Barnes Hospital in 1958 for a fractured right ankle . At that time she was apparently in good health except for the fracture . She first noted weakness of the lower extremities in June 1961 . Weakness progressed gradually until she was forced to pull herself up from a chair, although she could walk once she was on her feet . She also complained of aching in her thigh muscles . On her second admission to Barnes Hospital in line 1962 examination revealed no abnormalities except for weakness of the quadriceps and hamstring muscles bilaterally . An extensive laboratory work-up, including a lumbar puncture, was entirely negative except for a 10 per cent eosinophilia in the peripheral blood . Roentgenograms of the spine showed degenerative arthritis . An electroinyogranl revealed diffuse, scattered hyperirritability of muscle fibers . There seemed to be some improvement in the patient's condition following dexamethasone therapy . In March 1963 the patient noted generalized weakness in both upper extremities and transient blurring of vision . These symptoms became progressively more severe . In July 1963 she noted weakness of the fingers for the first time . On her third admission to Barnes Hospital in September 1963, there were extensive ecchymoses on the extremities and immature cataracts . The muscles of the hands were atrophied . There was marked weakness of the muscles of the
shoulder girdle and the pelvic girdle . Extensive laboratory tests were again normal, except for a protein-bound iodine level of 3 .4 pg. per cent . An electromyogram showed mild diffuse fibrillation . The patient was given an ACTII infusion for two weeks during which time there seemed to be some improvement . She was discharged from the hospital on a regimen of clexamethasone and triiodothyronine tablets. There was little change in her condition during the next ten months, but during the months of July and August 1964 her weakness progressed steadily and by late August she was completely bedfast. Her final admission to Barnes Hospital was in September 19694 at which time examination revealed a Cushingoid appearance, tachycardia and fever . There were multiple ecchymoses over the extremities . The blood pressure was 150/ 75 mm . Hg . There was further atrophy of the muscles of the hands and profound weakness of the muscles of the shoulder girdle and the pelvic girdle . The abdominal reflexes were absent bilaterally ; all other reflexes were normal . Blood counts were normal . Urinalysis revealed many bacteria and 6 to 20 white blood cells per high power field . Urine culture yielded a heavy growth of Esch. coli . Evidence of a urinary tract infection disappeared following ampicillin and later tetracycline therapy . The fasting blood sugar was 102 mg. percent . Spinal fluid was again normal on examination . The patient's many roentgenograms and electromyograms will be discussed subsequently . Histamine refractory achlorhydria was discovered at this time . Thirty-three days after the patient's admission to Barnes Hospital, diffuse abdominal pain developed and she died forty-eight hours later after an emergency abdominal operation . Let us first consider the major underlying disease from which this patient was suffering . Dr. Levy, would you discuss this patient's neurologic findings? DR . IRWIN LEVY : The patient's presenting complaint was weakness getting out of a chair . This would indicate muscle weakness of the pelvic girdle ; that is, a bilateral and proximal muscular abnormality . This particular pattern suggests an underlying muscle disorder rather than a neuropathy . It can be seen in either muscular dystrophy or in myositis . DR . REINHARD : Dr . Landau, electromyograms were obtained in this patient on three AMERICAN JOURNAL OF MEDICINE
Polymyositis different hospital admissions . The first two were interpreted as showing abnormalities more in keeping with a peripheral neuropathy than a myopathy . Would you discuss these records and tell us how you interpret them? DR . WILLIAM LANDAU : Abnormalities were present on each of the electromyograms . The most significant finding was the small, low voltage, I msec. potentials which occurred when the muscles under study were relaxed. These are defined as fibrillations and they represent hyperirritability in the muscle fibers . Another phenomenon observed in this patient was quite complex motor unit potentials indicating relatively poor synchronization and probably diminished populations of muscle fibers responding to anterior horn cell activity. In 1962 there were also some unusually large motor units, some which fired in doublets, and one locus of fasciculation . These are suggestive of a neuropathic process . Fibrillation indicates that something is definitely wrong with the muscle ; the muscle fihers are hyperirritable . The most common condition leading to fibrillation is denervation of the muscle . But the same kind of hyperirritability can be due to primary muscle disease and there are three quite reasonable pathogenetic mechanisms by which this may take place . First, an inflammatory process damaging the metabolism of muscle membrane could produce hyperirritability directly . Consider that a muscle fiber is quite long and usually has more than one end-plate which connects to one parent axon . A second mechanism confirmed by histopathologic studies is focal necrosis in a muscle fiber which disconnects a segment from end-plate regions . Thus, that segment is, in effect, denervated even though its motor neuron survives . Studies' have shown what happens to the main part of the muscle fiber when it is deprived of end-plate innen-ation . The excitability of the membrane increases greatly. Whereas the normal muscle fiber away from the end-plate is relatively insensitive to acetyl choline and mechanical stimulation, following a period of divorce from the end-plate region, it becomes hyperexcitable . The same physiologic changes in the main muscle fiber have been produced by chronic poisoning with a pharmacologic 1 THESLRFF, S . Effects of motor innervation on the chemical sensitivity of skeletal muscle . Physiot. Rev., 40 : 734, 1960 .
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end-plate blocking agent, botulinus toxin . These effects probably involve something more than a loss of the intermittent traffic of action potentials at the end-plate . In any case, one can produce electromyographic changes of denervation without anatomic denervation . Finally, there is pathologic evidence that inflammatory process in muscle may involve intramuscular nerve branches themselves in a focal inflammatory neuritis . The motor unit changes that were seen in this patient can be encountered in either myopathic or neuropathic processes related to the chronic patterns of loss of muscle fibers in the motor unit population . This may happen when single fibers fall out in a myopathy and may persist when new nerve branches grow out to muscle fibers that have been damaged or orphaned by the diffuse pathologic process. In the course of destruction of single muscle fibers, fewer join in the population of the discharging motor unit ; thus, a low voltage polyphasic discharge associated with effort is commonly observed and is called a myopathic motor unit . If the motor unit pattern is prolonged, or of particularly high voltage, the finding sug gests that nerve disconnection may have been followed by re-innervation . Such units are typical in chronic and partially recovering neuropathic disturbances and some were observed in 1964 . Re-innervation units may be large if a parent axon branches widely . These are commonly observed in motor neuron disease in which there is a decimation of the anterior horn cell population and surviving motor neurons put out collateral nerve branches within the muscle to pick up the orphaned muscle fibers . Thus, the surviving motor unit is larger than normal . In summary, the most convincing evidence indicates that this patient had a chronic irritative condition involving muscle . The finding of fibrillation per se does not distinguish between denervation and a primary myopathic process . The only direct test we have of peripheral nerve function, the conduction time, was normal in this patient . But normal conduction time does not exclude a neuropathic process and motor unit findings suggestive of neuropathy were observed . DR- REINHARD : Dr . Berg, you saw this patient during her second and third hospital admissions . If I read your notes correctly, you
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believed this patient had a polymyositis rather than a polyneuritis . Would you tell us why you came to this conclusion? DR . LEONARD BERG : On clinical examination there was never really anything to suggest that either the peripheral nerves or the anterior horn cells were involved. In addition to the fact that a pattern of proximal weakness was always present, the tendon reflexes remained normal ; there were never fasciculations, sensory changes or spread to the bulbar musculature . Throughout the patient's course, the clinical picture was always that of a primary myopathy and not that of nervous system disease . DR . REINHARD : Dr. Weiss, do you have anything to add to Dr. Berg's comments? Do you think that this is a polymyositis? DR. STUART WEISS : The weight of evidence is in favor of a myopathy . I would agree with Dr. Berg . DR. REINHARD : Dr . Klinkerfuss, we do not have any direct evidence that this patient had a malignant tumor, but various neuropathies and myopathies occur in association with tumors . Would you describe the neuromuscular disorders that may result from metabolic alterations caused by cancer, excluding direct nerve or muscle involvement by cancer? DR . GEORGE KLINKERFUSS : There are several central nervous system complications of distant malignancy which I will not discuss at this time. When the peripheral nervous system and muscle are considered, about four entities have been separated on clinical grounds and attributed to nonmetastatic complications of malignancy. In a given patient, these entities may be manifest in any number of combinations . Probably the most rare, and therefore the most likely to be discussed first, is the Eaton-Lambert syndrome . This is a defect primarily in neuromuscular transmission . Secondly, a pure sensory neuropathy is described and fairly well accepted . Thirdly, there is a motor neuropathy or anterior horn cell disease which is associated with carcinoma, and finally, there is a primary muscle manifestation called polymyositis, dermatomyositis, etc . This can be extremely low grade or rather fulminant . It can occur in a person years before the primary cancer is manifest on investigation . These would be the main points for consideration in association with carcinoma . DR. REINHARD : Do you think that the pattern in this patient was a type seen fairly often
in association with cancer? Would a polymyositis be one of the more common ones? DR . KLINKERFUSS : Yes, polymyositis is well documented to be the most common pattern seen with carcinoma and the patient's findings would fit this clinical pattern . DR. REINHARD : Dr. Perkoff, our neurologic colleagues seem to think that this patient had a disorder that is primary and that affected the muscles, not the nervous system . Are you willing to accept this as a myositis? DR. GERALD PERKOFF : The features this patient showed are quite compatible with the diagnosis of polymyositis, but without any biopsy information it is difficult to be sure the term "myositis" means inflammation . Frequently when we make the diagnosis of "polymyositis," what we are dealing with is progressive proximal weakness of relatively late onset and on biopsy we are often very disappointed. We do not know what else to call it, so we call it polymyositis . DR. REINHARD : It is surprising that a biopsy was not performed in this patient . It might have been of great help, might it not? DR. PERKOFF : Frankly, I just assumed the information was available but that it was left out of the protocol . It is worth noting that some distal muscular weakness subsequently developed. The patient became unable to write, her hands were clumsy, and it is entirely possible that she had a peripheral neuropathy . We may be dealing with two muscle diseases . First, there was the underlying disorder which brought the patient to the hospital and which might be called a primary myopathy, or neuromyopathy. Then she was treated extensively with steroids over a long period of time and recognizable features of Cushing's syndrome developed. We know that both in spontaneous Cushing's disease and in that induced by exogenous steroids, a proximal myopathy may occur, Frequently it is difficult to know whether the underlying myopathy being treated with steroids has become more acute or whether a second disorder has been added as a result of steroid therapy . DR. REINHARD : What about the possibility of a third type of myopathy? This patient was a rather heavy drinker which raises the possibility of an alcoholic myopathy . DR. PERKOFF : If one approaches this kind of problem from the standpoint of late onset of proximal muscle weakness, then one need not AMERICAN JOURNAL OF MEDICINE
Polymyositis call this polymyositis per se . It could have been a neuropathy associated with cancer. It could also have been a chronic myopathy and neuropathy associated with alcoholism . If she had been a heavy drinker and had continued drinking throughout her course, there is nothing in her history incompatible with that diagnosis . However, as we have stated here before, in the absence of more certain history, and without elevated enzyme levels and/or a biopsy, we cannot make that diagnosis . If this patient had been a man with symmetrical proximal weakness beginning after the age of fifty, according to some studies we would have as much as a 70 per cent chance of harboring a malignancy . 2 In women beyond the age of fifty with acquired proximal muscle weakness, the incidence of cancer still is about 25 per cent . The possibility of an association with tumor then, remains a real one at this point . DR . REINHARD : Dr . Perkoff, could you tell us something about the incidence of polymyositis and myopathies in association with various types of cancer . Is there any particular type in which this is most common? DR . PERKOFF : Most of the cases have been reported with three kinds of cancer : carcinoma of the lung, particularly in men ; carcinoma of the ovary and carcinoma of the breast . Of these, there is always concern that the high incidence in these tumors is only a manifestation of the frequency of the tumors ; this would be particularly so with cancer of the lung and breast. But in carcinoma of the ovary, there seems to be some discrepancy between the incidence of the tumor itself and the incidence of associated myopathy . However, almost every kind of tumor has been recognized as associated with this kind of process, so there is no known specificity about the histology of the tumor . DR . REINHARD : We are all delighted to have Dr. Irving London with us here this week as visiting professor. Dr. London, a slight eosinophilia was found on several occasions . Ten per cent eosinophils and 4 and 5 per cent eosinophils were recorded on differential counts of the peripheral smear during separate hospital admissions, Several differential counts showed no eosinophils at all . Is this mild and intermittent eosinophilia pertinent to any one of the ' SHY, G. M . and SILVERSTEIN, 1 . A study of the effects upon the motor unit by remote malignancy. Brain, 88 : 515, 1965 . VOL . 46, FEBRUARY 1969
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diagnoses we have been discussing? Do you think this patient might have dermatomyositis without a skin rash? DR . IRVING LONDON : This patient has a history of allergy of a rather indeterminate nature . The eosinophilia could have been associated with an allergic state or it could have been associated with an underlying neoplastic p rocess . i t is not clear why the eosinophils disappeared completely unless this was due to the steroid therapy . In a word, the eosinophilia is difficult to interpret but is compatible with an underlying neoplastic disorder . DR . REINHARD : I am very glad you brought out this point . I think this needs emphasis . We do not ordinarily think of eosinophilia as being a manifestation of cancer, but there are reports in the literature 3 of patients who have had eosinophil counts even up to 50, 60 or 70 per cent, in which the cause was apparently a tumor. In my own experience, this has usually been quite a large tumor, not an occult tumor, however. I would like to quote from an article on dermatomyositis by A . McGehee Harvey,4 "The clinical features of dermatomyositis are variable both in their intensity from case to case and in the pattern of onset which may be gradual or abrupt . At one end of the spectrum are the acute cases with fever, generalized muscle tenderness, weakness, edema and the characteristic heliotrope skin eruption . At the opposite extreme are the cases of chronic polymyositis, usually in older patients, who slowly develop weakness of the girdle and proximal limb muscles and who have minimal or no skin involvement and no constitutional signs ." Certainly this end of the spectrum fits in perfectly with our patient today. Dr . Perkoff, is there any difference between dermatomyositis and polymyositis, or are these different clinical manifestations of the same disease process? DR . PERKOFF : The answer to that question is not known . There are other grades in between straightforward dermatomyositis and polymyositis. Patients may have a lupus-like disease or have lupus with myositis ; some have features of rheumatoid disease . In others, the • TsAAcsoN, N . H. and RAPOPORT, P . Eosinophilia in malignant tumors . Ann . Int . Med., 25 : 893, 1946 . • HARVEY, A . MEG. In : Section on Diseases of Connective Tissue. Cecil-Loeb Textbook of Medicine, p. 456. Edited by Beeson, P . and McDermott, W . Philadelphia, 1967 . W . B . Saunders Co .
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lupus or rheumatoid features predominate . Polymyositis may be very acute, just like dermatomyositis, but without a skin rash . I do not really believe it is possible to make much out of the fact that there is or is not a skin rash in patients with inflammatory muscle disease . The muscle disease may look exactly the same. From a pathogenetic point of view, when people have looked for evidence of immune abnormalities in patients with polymyositis, it has not been very easy to find them . Specific antimuscle antibodies cannot be detected regularly in the serum of such patients . On the other hand, some such patients have accelerated turnover of immunoglobulin . Dr . R. Dean Wochner at St . Louis City Hospital is studying some of these patients now, but it really is not possible to decide whether or not the two syndromes are the same or different on the basis of the information presently available. DR . REINHARD : Now we come to a consideration of the catastrophic events of the last fortyeight hours of this patient's life . Thirty-three days after the patient was admitted to Barnes Hospital for the fourth and last time, she had severe abdominal pain . It was most severe in the epigastrium and perhaps in the lower substernal area . There was marked tenderness in the epigastrium . An ulcer diet was instituted and the patient was given antacids . The next day an exploratory laparotomy showed evidence of an acute abdomen, and she died forty-eight hours after the onset of the pain . Dr . Torrance, would you please discuss the patient's roentgenograms? DR . DANIEL TORRANCE : A plain film of the abdomen taken at the time when the patient was having the abdominal pain showed markedly dilated loops of small bowel . The location is that of dilated jejunum and there was increased space between parallel loops indicating thickening of the bowel wall . These findings are consistent with proximal small intestinal obstruction . I would like to flash back in time and review the patient's many chest films . Those taken in 1962 and in 1963 were perfectly normal . There was a subtle change in the mediastinum on the chest films taken in 1964 during her last hospital admission . Further, there was a more obvious change in the lung fields . Late in her final hospitalization, a very bizarre looking central density developed in the right mid-lung field and a peri-
hilar density which obliterated the vascular outline of the hilar shadows . The lesion in the right lung increased very rapidly during a one day period and within two days there was evidence that something catastrophic had developed with a massive right pleural effusion and rather striking mediastinal widening behind the aortic arch . This suggests that an acute hemorrhage may have occurred and that perhaps it was related to the patient's abdominal catastrophe . DR . REINHARD : Dr . Peterson, at laparotomy a volvulus was found . This involved the upper part of the jejunum . The involved bowel was 18 inches in length ; it was pink . The volvulus was reduced and unwound, and the jejunum was dropped back into place . Nothing was resected . Would you tell us what some of the causes of volvulus are and would you comment specifically on volvulus of the upper part of the jejunum . I understand this is rather rare, is it not? DR . MALCOLM PETERSON : It is rare . Dr. Reinhard, I cannot think of anything that would be suggestive of a predisposing factor for development of this patient's volvulus . She was obese ; volvulus is sometimes associated with emaciation . The speculation is that the weight loss and changes in fat around the bowel and mesentery allow pendulous portions of the bowel to rotate on the mesentery . The possibility of an internal hernia is always certainly present, but I think it would have been described at surgery. So all I can say is that this is indeed one of the rarest portions of the bowel to be involved by volvulus ; factors which might predispose to it, including congenital malrotation and internal hernia, were not present . Interestingly enough, for some reason volvulus of the intestine is generally seen more commonly in men than in women . There is the possibility that there could be a tumor in the intestine . Since the possibility of an occult neoplasm is a real one, I pursued this to the extent of looking at several monographs . I can find no reference to this being a likely cause for volvulus . DR . REINHARD : If there were a tumor we presume that it would have been found by the surgeon, unless it was very small . Dr . London, this patient had achlorhydria, even after intensive histamine stimulation . A Schilling test showed only 4 .3 per cent urinary excretion of AMERICAN JOURNAL OF MEDICINE
Polymyositis the tagged vitamin B 12 . However, at no time did the patient have anemia ; the red blood cell indices were perfectly normal, and no hypersegmentation of the polymorphonuclear leukocytes was ever noted . It seems clear that the patient did not have pernicious anemia . It is noteworthy that the Schilling test was performed just six days before the patient had severe abdominal pain which was shown on laparotomy to be due to this volvulus . I wonder if you will tell us where vitamin B 12 is absorbed in the gastrointestinal tract, where you think the releasing factor comes from, and whether it is possible that the patient had a disturbance of the gastrointestinal tract six days prior to the development of the acute volvulus that might have interfered with vitamin B12 binding, vitamin B, 2 release from its binding to intrinsic factor, or subsequent absorption into the blood stream? DR . LONDON : The physiologic absorption of vitamin B 12 requires prior binding to intrinsic factor and the vitamin B 12-intrinsic factor complex travels from the stomach and upper small intestine to the lower ileum where vitamin B 32 is largely absorbed. The orientation of intrinsic factor-vitamin B 12 complex toward the mucosa of the ileum also requires inorganic calcium . You raised the question of the mechanism of releasing vitamin B 12 from the intrinsic factor complex . Very little is known about it but I would guess that the release action occurs in the mucosa of the ileum . Your question of whether the low values on the Schilling test were related to a disturbance in the gastrointestinal tract prior to the development of a volvulus is reasonable . Although the patient did not present symptoms suggestive of a chronic gastrointestinal disturbance, she did have achlorhydria and some diminution in intrinsic factor may have developed . The absence of evidence of pernicious anemia does not rule out a diminution of intrinsic factor because if she had had normal stores of vitamin B 12 , it could require as much as two to three years to deplete these stores. It is reasonable therefore to raise the question of a more chronic gastrointestinal disturbance . DR . REINHARD : Of course, the other possibility is that some of the urine was lost and the results of the test therefore were not valid . The day after laparotomy the patient was hypotensive . The following day she began to VOL .
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have difficulty in breathing . She became unresponsive . Endotracheal suction yielded a large amount of yellow fluid . The striking changes described by Dr . Torrance were seen on the chest films . Dr. Roper, what was happening during these last forty-eight hours to cause this remarkable change in the appearance of the right side of the chest? DR. CHARLES ROPER : Although this patient's history is quite compatible with occult carcinoma of the lung, there is no evidence to support this diagnosis . Fever and an infiltrate in the lung suggest the development of a pneumonitis and the most likely etiology of the abnormalities of her last chest films was a severe aspiration pneumonitis, which occurred either in the immediate postoperative period or during the time of surgery. Both an underlying pneumonia and an episode of aspiration can give rise to a massive effusion . She had very little atelectasis ; this was predominantly effusion . DR . REINHARD : Dr. Smith, what do you think of the possibility that this was a vascular accident, a ruptured aneurysm, for example? DR . JOHN R. SmiTH : On the basis of the information Dr . Torrance has given us and the terminal x-ray picture of a marked widening of the mediastinum above the heart, I wonder whether or not there may have been aortic disruption with bleeding into the mediastinum and into the pleural space- This, of course, is conjectural . Ordinarily, this event is accompanied by considerable pain, which did not occur here . However, this is a distinct possibility and I would personally favor this diagnosis . An interesting aspect of this disease is that, if indeed it is a dissecting aneurysm, this patient also had mild hypothyroidism managed by exogenous thyroid. It was noted years ago that hypothroidism is associated with medial cystic necrosis of the aorta, particularly when this is complicated by hypertension . This patient did not seem to have hypertension, therefore the argument for this disease is considerably weakened . On the other hand, there is no evidence of overt atherosclerosis of the aorta. The patient did not seem to have syphilis, but the possibility remains that the aorta may have eroded, if one wants to argue that this was deterioration of the aorta . DR. REINHARD : We will have to terminate our discussion now. I therefore present as our
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final diagnoses a primary myopathy, possibly complicated by steroid therapy, possibly aggravated by alcohol . We are concerned about the possibility that the patient might have had an occult tumor and that this was a cause of the myopathy. The patient certainly had iatrogenic Cushing's syndrome, and I agree with Dr . Smith that the terminal event was probably a rupture of an aortic aneurysm of the chest . I cannot account for the sudden appearance of pleural fluid on the basis of an aspiration pneumonia nor can I fit the volvulus in with the other events at all, and I believe it was a purely coincidental event at a very inopportune time . PATHOLOGIC DISCUSSION
DR . JOHN KISSANE : This case presented very interesting anatomic findings : some are purely objective, some are the basis for what we believe is a well documented interpretation, and others remain the subject perhaps for speculation . We do have the cause of death . The entire middle lobe and the apical portion of the lower lobe of the right lung were consolidated, both grossly and microscopically. We would have to call this lobar pneumonia . Gram stains showed lancet-shaped diplococci, and histologically the lesion was typical of pneumococcal lobar pneumonia . Succulent nodes were described presenting into the right pleural cavity. The aorta was normal . No tumor was found . Peripheral nerves and muscles were examined in considerable detail . We have to say that all accessible nerves were normal . There was no inflammation, no fibrosis and
Fm. 1 . Larvae of T . spiralis in jejunal submucosa . Hematoxylin and eosin stain, original magnification X 120 .
no demyelination. Skeletal muscle, itself, was not histologically normal . The abnormalities were somewhat subtle and consist of a variation in fiber size and general diminution of fiber size, more or less randomly distributed through the skeletal muscles, not in a fascicular or motor unit pattern which we would recognize as neurogenic atrophy . There was, in addition, some increase in sarcolemmal nuclei which gave an impression of cellularity to the skeletal muscle. There was no bona fide interstitial inflammatory reaction, no necrosis and no acute component to this rather nonspecific patchy atrophy of the muscle . Now let me direct your attention to the previously volvulated segment of the jejunum . We saw a somewhat inflammed submucosa and, in addition, forms (Fig. 1) in the crypts of the intestinal glands . These are the transverse sections of worms which microscopically can be identified as Trichinella spiralis . This infestation was particularly heavy in the mid-jejunum . Every section showed, in every high power field, really dozens of larvae of Trichinella . Available sections of skeletal muscle showed (Fig . 2) transverse sections of larval Trichineae in the interstium of a few of the skeletal muscles . These were not encysted ; they were not in the muscle fibers themselves but free in the interstium, presumable in transit from the vasculature within the skeletal muscle bundle . This patient then had trichinosis in the intestinal stage at the time of her death . I think it is highly probable that disturbed intestinal motility resulting from the extremely heavy intestinal infestation led to the volvulus . It was James Paget, otherwise notable, who as a young medical student first established that the calcified granules occasionally observed in human skeletal muscle were endoparasites . The name Trichina spiralis (later changed to Trichinella spiralis) was applied to the worm by one Robert Owen, later to become famous for his discovery of the parathyroid glands during a dissection of an Indian rhinoceros. One of the earliest students, and certainly the most illustrious, of experimental trichinosis was Rudolph Virchow. The very stringent federally regulated inspection of pork carcasses in force in Germany (and by imitation, elsewhere in western Europe) toward AMERICAN JOURNAL OF MEDICINE
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Polymyositis the end of the last century was, however, as much a product of Virchow's role as the foremost liberal politician of his day as it was a tribute to his standing as a scientist . There were, in Germany in 1895, some 25,000 federal functionaries engaged in the inspection of pork products, a figure very nearly equal to the strength of the standing army of the United States in that same year .' There are some curious and provocative facets to the epidemiology of trichinosis. Many investigators have remarked upon the tendency of trichinosis to occur in ministers and in teachers, pursuers of historically mendicant professions traditionally dependent upon dinner invitations to eke out their mite . Less well known is the tendency for trichinosis to afflict physicians, who ought to know better . In one outbreak in California, three of twentyone persons afflicted were physicians . With regard to the biology of Trichinella spiralis, we can reiterate that the parasite pursues its life cycle in a single definitive host . More importantly for our purposes in interpreting this case is the fact that trichinosis, unlike many endoparasitoses, is a relatively acute disease, the several stages of which have been experimentally fairly narrowly delimited chronologically . Release of encysted larvae from ingested food occurs in the duodenum and upper part of the jejunum within hours, and liberated larvae promptly mature, If both sexes are present, copulation occurs, maturation and mating of adult worms requiring about five days . The female Trichinella is ovoviviparous, that is, delivers alive from her vagina, larvae which have hatched in utero . A single gravid worm delivers 1,000 to 1,500 larvae at a rate of one per half hour over many weeks . Larvae reach the circulating blood via intestinal lacteals and are carried to skeletal muscle where they leave the vasculature, coil and encyst, processes requiring about seventeen days . The point of the recitation is that the sequence in the evolution of trichinosis, dated from ingestion of infested meat, occupies only weeks . One episode of intestinal and extravascular muscular trichinosis cannot, therefore, explain our patient's long history of neuromuscular disturbance . Detailed review of available microsections of GOULD, S . E ., Trichinosis . Springfield, Ill ., 1945 . Charles C Thomas . VOL .
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FIG . 2 . Larvae of T . spiralis in interstitium of skeletal muscle . Hematoxylin and eosin stain, original magnification 280 .
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skeletal muscle did, at length, however reveal old, indeterminately old, calcified cysts of Trichinella larvae in one section (Fig . 8) . Our patient, therefore, died of lobar pneumonia after sustaining a mid-gut volvulus in the course of intestinal trichinosis. She had had trichinosis, evidenced by old intramuscular cysts, at least once before . We have no other morphologic explanation for the patient's previous impairment of neuromuscular function . DR . REINHARD : Dr. Perkoff, do you have any comment on the polymyositis or the myopathies? Do you think this really could be due to the trichinosis? DR. PFRKOFr : I do not really see how we can say whether or not this resulted from old trichinosis . Certainly there are cases on record in which polymyositis supposedly resulted from trichinosis, but usually many more cysts are found in the muscle. This patient did have eosinophilia throughout the entire ten years she was seen here .
FIG . .1 . Empty cyst in skeletal muscle. Hematoxylin and eosin stain, original magnification x 200 .
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DR . REINHARD : Ten per cent only once. On all other occasions the eosinophil counts were within normal limits . DR . PERKOFF : Apparently the eosinophilia in trichinosis is variable . In at least one-fourth of the patients with trichinosis there is never any eosinophilia at all, and when present it may be intermittent, so I would not say that this could not be trichinosis . We did not see any vacuoles like those found frequently in steroid myopathy. DR . KISSANE : There were no features of any specific myopathy. DR . REINHARD : Dr. Levy and Dr. Berg, this was your patient. You knew what the autopsy showed and perhaps you have had longer to think about this than the rest of us . Do you think that trichinosis could account for this patient's myopathy? DR . LEVY : I would say that the clinical course was certainly different from that which is clinically typical of trichinosis . DR . REINHARD : I would agree with that! DR . LEVY : There were clinical representations of an acute phase. Ordinarily it occurs
with the invasion of muscle . Certainly none of the ordinary findings ever occurred in this person's history . I think there is some reason to doubt that trichinosis contributed to the myopathy. DR. REINHARD : Dr . Kissane, did you look up in the literature and evaluate cases similar to this attributed to trichinosis? DR . KtssANE : I did not find similar descriptions in die literature, but muscles certainly may become atrophic . Trichinosis is an acute disease and ordinarily self-limited. However, she certainly had had trichinella infestation at least once, and perhaps more than once . Pathologic diagnoses were widespread but slight atrophy of skeletal muscle fibers not typical of neurogenic atrophy (history of clinical diagnosis of polyneuropathy treated with steroids and ACTH) ; empty cyst of T. spiralis in deltoid muscle ; larvae of Trichinella spiralis in the jejunum and in skeletal muscle ; recent abdominal incision (reduction of volvulus one day before death) ; lobar pneumonia, middle and lower lobes of right lung ; pleural effusion (800 ml .) .
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