Document dXMEwQ6qy7pRRYRoQQZvDLGG

/>. S OFIRIOS OS THE ETIOLOGY OF ILLNESS gtIFFE? H? BY a t h e s s T^h io Eatme of Illness t history > occupa tftshal e?rpo^tge> coarse and Gindinsa * ?*' | The patient is e n&rried white man of 53 a painter and paper-hanger by tz-ade. Sine Juno of 1945 he has suffered from a progressively incapacitating disease., characterised at the ons@t by slurring of speech, then by ^jumping, '* weakness and wasting f the muscles of the upper areas and thorax, narked weight loss despite adequate food ingestion, progressive loss of the power of speech, difficulty in swallowing foods, and gradual restriction of food and fluid intake to puitacecus foods to avoid choking and nasal regurgitation. In the laat 18 months a habit of a humorless laugh when under emotional stress, a hanging jaw, and a drooping mouth have developed. The patient always preferred papering to painting, but was boss painter for the Fred Eglehoff Company for 1 1/2 years before World War II. As foreman he nixed the paste into paints end was in the rood when spray painting was done by others. Curing this period of employment none of the men or himself had colic or other Ejmptcais attributable to lead exposure. In Hcveaber 1242 all occu-~ patiensi exposure to lead ceased when h vent into a wrar plant as a maintenance mechanic. The first symptoms of the present illness began seven months later.* The informants for the history were the patient and his wife, and two carbons from the Industrial Ccmalscion's file, OD 44675- One of these carbons is a recommendation by Charles l Darker, who states B... (the patient) first became ill about June, 19**12........ * This is specifically denied by both the patient and the wife, who state the illness began in June, 1945, months after the patient left theemploy of the Eglehoff Company. HE 0016654 In the three years th patient has been ill fee lias sanght the advice of many physicians. Among other prmedufes\.X-Bfty of the skull and neck and a lumbar puncture vcr performed under the direction of'Dr. C. U. Cronick of Xoungstovn, Ohio? in January., 1945- On the advice - of this physician a claim for-disability foroccupational disease was filed, the claim" ms denied- by the industrial Commission in December, 1945* Vlth the help of C. H. Knisley and Associates' the case mas- appealed. In June, 1946, the Kedios.1 Appeal Beard refused- to allow the claim. Qa the advice of Mr. Kaisiey the case vas then referred to us. On physical examination the patient was found to be a largeframed man with marked, wasting and weakness of the muscles of mastication, the neck, the thorax and the upper ms. He made a few gi unting noises when trying to talk, and seemed unable to articulate'. Most of the time- the jaw hung down with the mouth open, the wasted. tongue immobile, There was little change in expres sion, but the folds of the skin were not smoothed, there were constant irregular flseiculalions involving particularly the muscles of the 'thorax, shoulder girdle and upper am. the jaw jerk was present and gag reflex active, the- deep tendon and superficial skin reflexes were 11 active, with no clonus or pathological reflexes. There was marked ago-edema. Bo sensory changes, ataxia, or loss- of position or vibratory sms-were found. He seemed oriented and aware, and annoyed by the humorless laugh that he uttered at frequent intervals during the examination. Laboratory studies were limited to the study of the spinal // A Y <J - C A fWWf and blood and urine samples for lead. The cerebrospinal fluid dynamics were normal, end the spinal fluid was clear and HE" 0016-655  5* colorless. It contained one lymphocyte per cubic centimeter. fh Paady was negative, fh protein ms 64 mg. per cent:ikeWassermann % and Eagle negative#: and the gold Sol 000 000 0000. '^Pb urine con tained 0.0S mg. of lead per liter, and tbe blood 0.0p3 mg. of lead per hundred grams. Hiff.eren:t?:ldl,. diagnosis The differential diagnosis of tbe patient fa syndrome can be considered as among tbe many conditions in which progressive mating and atrophy of muscles occur, and from other diseases in which bulbar signs and symptoms are clearly in evidence. Such illnesses as thyrotoxicosis, arthritic muscular atrophy, syringomyelia, cervi cal rib, myotonia congenita, progressive muscular dystrophy# peri pheral neuritis, infectious neuronitis, cervical pachymeningitis, and secondary lesions of tbe affected nerves by neoplasm, have certain superficial resemblances to the patient*s syndrome, but a clinical knowledge of these syndromes and the studies of the patient rule out such conditions. Myasthenia gravis, tumors of the brain stem, multiple sclerosis, tuberous sclerosis, bilateral vascular lesions of the brain stem as from thrombosis or hemorrhage# central nervous system syphilis, and post-encephalitic end arteriosclerotic Parklnaonismus may cause bulbar or pseudo-bulbar signs; these conditions have all been ruled out by the studies of the patient. Tbe history, physical findings and laboratory studies are diagnostic of the bulbar type of progressive muscular* atrophy. Etiology of the presenting syndrome The immediate probifor decision in this case is whether the occupational exposure to lead caused the disease. This problem K 0016656 may be approached by considering the following questions s $1} to lead; (t) the etiology of progressive jmseoltt atrophy; (5) the evidence need la the past to attribute to. lead so efciologic role in the development of progressive' muscular atrophy* {6$ the character Of the oresentinc ssmotamatoloeT ; and . 171 the necessarv eriterl lead- containing pigments. Of importance are the facts he preferred papering to painting and did more of the formers the principal exposure to paints was as foreman for the Fred Iglehoff Company, ' during which tin there w ee no exposure to dry pigments, no spray painting by the patient, and no note of symptoas comsonly attributed to lead poisoning in himself or the erev; and the patient has never bad such symptoms, other than the parexyms of abdominal pain at intervals throughout the present Illness. It say be inferred that the patient has bed less exposure to lead than the average pro fessional house-painter, and that he has neither had symptoms he has attributed to lead exposure ether than the'present illness *nr had '.symptoms that m&i% "be"a ifc&lb^ed.''" ' *" (2) i'iffie relation between the occupational exposure to lead and the development of thf srndrome The patient had no occupational exposure to lead after, leaving the -employ of the Fred Sglehoff Company in the fall of and had none vhile working as & maintenance mechanic for a KE 0016857 r pleat, according to the patient and his report of the plant physician*s statcBont* Ttsla'physician, Dr* Kelson, is also one . - _ ,^>- 7 1 - . ,.... , V... of the patient*s attending physicians. The preset Illness did " - --* ' '. ' pfr'>'.Kv:;:fr,,v;.,. ,' <ir .t - , _.,Sfcr not begin until June of 1S&3* It may he concluded that the patient did not develop the first evidence of illness until many monthi after leaving the employ of the instant employer.: (5> The .extent of the present exposure to lead The illness has been steadily progressive sine# it began* -* ' ; ...... --- ' s- . V-" **< -. ' %* < .** 2 -- .- s''?.'. At th present tine the blood and urine lead levels are vlthin the norms! rang. This is proof that there has bees no recent hazardous exposure to lead. It stay be concluded that the patientrs illness has progressed in the absence of hazardous lead exposure. (%) The etiology of progressive muscular atrophy It is generally agreed that the etiology of most cases of progressive muscular trophy Is unknovn. The great majority of patients vith this disease have had no occupational exposure to lead. Also, the vast majority of 'patients vith hazardous occupa tional exposure to lead, and vith symptoms attributable to such exposure, do not develop this disease. Dr. Xeho has never seen or had brought to Ms attention a case of progressive muscular atrophy folloving undoubted lead poisoning.. The experience of Jemes Collier and V. Bussell Brain is the same? ml have never seen nor have I been able to find" in the numerous records of the national Hospital (in London) any cases in vhich undoubted lead poisoning has been followed by typical muscular atrophy (I). Hovever;, there re` scattered references in the literature in vhich this question has been elaborated. The first significant reference KB 001665 is tiis study 59 years ego by James J. ?utn (2) In Which he . reported on., eighty-six patients with % variety of obscure disuses of the nervous cyst.....,... In none of these esses were the classical symptom of lead poisoning..... .unequivocally present.* la the urine of 48 patients lend wa present,, in the remaining it was absent on single determinations. **lh (five) oases of progressive muscular atrophy shewed so lead (in the urine) *" She first authoritative specific discussion of the problem was by Gowers* who stated, 'General muscular atrophy say result from lead poisoning, but this form 1 not, as a rule, progressive in character when the cause has ceased to sot. It resembles the ordinary fora of progressive muscular atrophy, however, in seat and features and thus differs from the comma atrophic palsy of the extensors that is produced by lend." O) He later described two forms of lead palsy, the first, local muscular paralysis followed by wasting, "the second form, characterised by primary atrophy, occurs specially in the intrinsic muscle of the hand, but 1 sometime extensive and irregular in Its distribution, affecting many muscle in all four limbs. The mating is slow, and accom panies , instead of succeeding loss of power (h) . Be described no cases with bulbar symptoms. He went on to say *%he cases of general muscular atrophy ,f at*tfaii. origin scarcely ever present any difficulty (in diagnosis) because they usually supervene on severe lead poisoning that has caused characteristic symptoms* (5). He cautioned that Hthe recognition of lead-poisoning depends, first, on the character of the symptoms of nerve disturbance; secondly, , on the existence of other indications of the presence of lead in K" 0016659 . , Vtf- T< / the jsystea; thirdly, on the discovery or the feet that lead Is . catering the.systesi. fourthly, oathe fact that lead is leaving the es s Lea in the urine, /The diagnosis can tails' *#Mte a high degree of probability when tiro or sore indications are combined ar(6). Gowers mm careful to distinguish between "general muscular atrophy* end progressive muscular atrophy.* This distinction ms lost in an article by S. A .X, mIson, published in 1907 (7). Beoause this is the only paper in. %%lch the diagnosis of "amyotro phic lateral sclerosis of toxic origin* has been specifically entertained, the cases which were used as examples are suarnrieed below. '- Case 1. , c. - ..t.j: r. - '-.C A compositor, aged Hj, began his trado at the age cf twelve and continued until incapacitated by 'wrist drop at thirty-fire. He had had colic about three months before. lie ceased work as a compositor, but still had occasionally to do with lead..... Three years ago the weakness and wasting seemed to have ccssmenced afresh, as he began to notice a certain difficulty in keeping his head erect, end a certain feebleness about his shoulders. On examination the findings included profound muscular atrophy involving principally the upper arm muscles, with some weakness, atrophy and spasticity of the anterior tibial muscles, a steppage gait, s'typical extensor plantar response on the.left, and a distinct tendency to extension on the right. There were no bulbar signs, Although his articulation has become a little indistinct." Case_g. A tinsmith of ?2 with 16 years experience had never suffered fro lead colic, although there was % good deal of lead in the solder used by him.* He developed cramping and weakness in extension in the fingers of the left hand, which progressed to K 0016660 complete wist drop la six months A year later this began end progressed la the right hand, and three months before ho was seen he began to dreg the toes of the right foot shea lie miked, end to suffer fre very severe cramps la the calves of the legs: aM the . tees*, iher sere no bulbar sign. In eighteen iaosths* observation the msting and weakness of the extensor -muscles progressed with involvement of other muscle. groups.of the extremities* Constant - painful cramps in the calves continued. She deep reflores were ' brisk and -the plantar responses remained extensor. Case ihe patient am a ^-year-old engine fitter vho %s& not, apparently, caste into direct contact with lead. twelve years before he fitod) contracted syphilis " Sixteen months before he - was seen he began to notice weakness and numbness of the extensors of the right middle finger. Shis progressed to involve the other fingers, and the wrist* At the cad of the year' there was wasting of the forearm sad weakness of the right elbow and shoulder, three months before he was seen the same changes began in the left hand and arm. He had to hold up his heed with Ms hand to keep it from falling forward as ho walked, and he bad increasing difficulty in passing water. In addition to the findings of atrophy and slight spasm of the affected muscles he had Argy ll-Bobertsoa pupils, a tremulous tongue that appeared slightly atrophic cn the right side, and a double extensor plantar response. CesgJl* Was a 6>year old painter and paper-hanger-# who had had an attack of lead eolle at 60. Six months before he was seen he developed "sciatica a inf the right buttock and thigh, fhre months later had had cramping of the fingers of the hands, and developed a bilateral wrist drop. Os physical examimatioa he had complete double tf 0016661 wist drop, and eacng other findings exaggeration of the deep reflexes, slight spasm of the leg muscles, end no typical flexor responses to plantar stimulation. Seme of the patients Improved under observetlcm. So post* mortem studies were available. Wilson stamsarixed the salient features of the four eases* 1 In each there is the some unmistakable (except perhaps, in Case 3) source of poisoning, vis., lead,the action of vfcieh had coctimed over a considerable period. 2 In each the onset Is characteristic of an ordinary lead palsy, vis-, double drop-wrist. fhe degree and duration of this lead palsy before the appearance of other symptoms vary greatly in the different cases* 3. She lead palsy.*... .Is followed by progressive amyotrophy of irregular distribution, affecting flexors as well as extensors..... (and) is associated with cramps in the limbs, fibrillations in the diseased muscles, sometimes with involuntary sporadic movements, and with weakness proportional to the msting...*... W w&j conclude from study of these cases that Wilson does not follow Gower*a criteria in making the dialogic diagnosis, but that he likewise restricts tils cases to those *in which the onset is characteristic of lead' palsy.".. In Ms. textbook .(?) Wilson adds "two or three more examples have come to ay knowledge, since; the latest ' (If32) concerns a painter who soma eight years ago suffered from an attack of drop-wrist (left more than right) end made a partial recovery I on examination I found atrophic palsy of email hand muscles, also of forearm, fibrillary twitches, exaggerated deep reflexes (probable), extensor weakness with little or no spasticity, and unmistakable signs of incipient bulbar paralysis (meting and K-E 0016662 : V:# la. flickering tcngu* palatal ve&knesss, dycarthria,,,cto.) * The last important paper is by Brsmsell {9}... He Illustrates bis lecture by sever*! cases, one with radial p&lsy, with symmetrical motor neariti* of tbs upper limbs .; (one, of who did mot have involvement of the upper anas or glioulder gif^la), one with ; encephalopathy* and one with spastic paraphlegiai. The two cases of spasetx'tcal motor neuritis of the upper limbs resellIs. cases of progressive muscular atrophy-. However* Bmsveli makes & diagnos tic point of the observation that the cases did act progress, after the cause (?) (lead contaminated drinking waterj vas removed* These observations may be stsssasrlsedby the statement that the evidence used in the past to attribute to lead as eiiolo&ie role in the development of progressive muscular atrophy is tenuous and presumptive, but that no cases have been so attributed, that have not had peripheral mater palsy the presenting symptom. (6) The character of the presenting smrtoa&iology The Illness in the present ease began vith difficulty in articulation. Weakness of the forearm and hands is not prominent, even later in the course of the illness. '2he abdominal cramping has apparently been considered as evidence of lead poisoning. However, this has continued up to the present* is the proven absence (by blood ansi urine sampling) of hazardous load exposure. ; Cramping . of effected muscles may be present In pragieoslwe muscular atrophy. In summary, the presenting symptomatology was not peripheral nerve palsy, and w&a motcharaeterlsticof lead poisoning. (7) She necessary criteria for the diagnosis of lead poisoning In our opinion the necessary criteria for the diagnosis of lead poisoning are threat (1) there must have been sufficient HE 0016863 exposes to lead to cause intoxication; (2) the signs and symptoms present must tie these found in lead intoxication; and {>} the signs and symptoms must not he explained on some other basis. lone of these criteria are satisfied la. the present case* the assumption .., that lead': &&s a causative or contributory relation to the derelop* meat of the present illness is eeaqpletely conjectural, lo adequate basis for such a conjecture can he found from a study of the patient Conclusions 1* The patient is suffering from the toolbar type of pro gressive muscular atrophy* 2* The patient has had less exposure to lead than the average professional housepainter, and prior to the present Illness had had no symptoms attributable to lead exposure I the Illness did not begin until months after the occupational exposure to lead ceased; the illness has progressed in the absence of hazardous lead exposure; the evidence used in the past to consider lead an etiolo gical factor in the development of progressive muscular atrophy Is tenuous and presumptive, tout even so no cases have been so attri buted that have not had peripheral motor palsy the presenting symp tom; the presenting symptom in the present case vas not peripheral nerve palsy, and v&s not even characteristic of lead poisoning; and non of the criteria ve consider necessary for the diagnosis of lead poisoning are satisfied in the present case. 3* The assumption that lead has a causative or contributory relation to the development of the present illness is completely conjectural. So adequate basis for such a conjecture can be found' from a study of the patient and the pertinent literature. 8*15-46 - e OOI&G64 1. Collier, James, revised by W . Fussell Brain, Oxford Medicine, II. A. Christian, editor, Oxford University Press, 14. it- "b223. 5. Furness., Jsses J., Ga the frequency vith vhich lead Is found in .: the; ' iht: 'th#. sy^li^iololBf && " :: . c7h^r7o6n,ic9l7e-a9d91,p1o8is8?on. ing' . Boa ton, fed, an'a!'c 7l:'u%;jr-e77;*,h. t J..o..u..r.s.,.,.. lift J* Covers, W.fiv, A manual or diseases of the nervous sistm. ?. Blakis ton Phila., gad Wition,' lays'.1 j 47^ '" 4. ib.,id. ls>'51. ' ,0* ib 0Id* Jer.yoX* 6. ib., Id- j:959* 7. Wilson, 8.A.K., The amyotrophy of chronic lead poisoning! asyolhrophle lateral sclerosis of toxic origin, lev, of Ketiral* and Fsychiat., 5^41-433, 19o7* 8. lb-, Beurologj* edited,by A. B. Brace, Wilkins and Wilkins, 1940, 73a. 9. Bran^ell, Edvin, I marks on &os clinical pictures attributable to lead poisoning, viifc special reference to the neurological manifestations of pliaabism, Brit. Med J., July 18, 1931. KE- 0016865