IRRADIATED ERGOSTEROL POISONINGREPORT OF TWO CASES

PHILIP A. TUMULTY, M.D.AND

JOHN EAGER HOWARD, M.D.BALTIMORE

During the past five years there have been an increas-ing number of clinical reports regarding the use ofmassive doses'of vitamin D in the treatment of rickets,tetany, rheumatoid arthritis and various allergic states.1We shall make no attempt to evaluate the therapeutic

efficacy of vitamin D or its concentrates in these con-ditions but shall rather put out a suggestion of cautionregarding the possible ill effects that may follow, undercertain circumstances at least, the employment of mas-sive doses of the vitamin.That vitamin D and the irradiated sterol concentrates

may produce toxic reactions has been recognized formany years. Numerous writers have described theoccurrence of anorexia, loss of weight, nausea, vomit-ing, abdominal pain, diarrhea, muscular weakness, head-aches, polyuria and polydipsia in both man and animals.Acute intoxications in animals have resulted in comaand death.2 Only two or three deaths have beendescribed in man. These will be referred to later. Itis of interest that most of the patients who have beengiven massive doses of vitamin D have shown onlyminor evidences of intoxication and it is perhaps forthis reason that the more severe consequences of massivetherapy have not been appreciated. Thus McLean3says "the dangers of the toxic effects of these substances,while real, have been somewhat overemphasized," andSteinberg * echoes him.It is thus to encourage an attitude of respect for

the potential dangers which may lie in the employmentof large closes of ergosterol, under certain circumstances

at least, that we present these 2 cases in which a majormanifestation of ergosterol intoxication of a seriousnature was a prominent and interesting feature.

REPORT OF CASESCase 1.—History.—J. W., a white man aged 22, was admitted

to the medical service of the Johns Hopkins Hospital onJuly 23, 1941. The history revealed only the usual childhooddiseases. The system review was entirely negative. He hadnever had urgency, frequency, nocturia, hematuria or oliguria.He stated that he had never had venereal disease. He wasemployed in an airplane factory and had never been exposedto any toxic agents. On July 2 he had been struck by anautomobile and had fractured his left femur and left clavicle.His leg was immobilized in traction and on July 8 he wasgiven a large dose of a preparation of ergosterol containingSO per cent calciferol and 50 per cent of a mixture of lumisterol,tachysterol and toxisterol. During the succeeding twelve dayshe received approximately 750,000 international units of thepreparation daily. This medication was frequently given in aglass of milk. Throughout this period he ate a diet whichcontained 1.5 to 2 Gm. of calcium daily. At the end of twelvedays the patient complained of nausea followed by abdominalpain and later of vomiting, which became almost intractable.At this time the urine was examined and found to containmany hyaline casts and red blood cells. It is significant tonote that urine examinations prior to the administration ofvitamin D were entirely normal.He was therefore admitted to the medical service, where the

physical examination was essentially negative but for a frac¬tured left femur and left clavicle. Blood studies showed redblood cells 3,730,000, hemoglobin 8.5 Gm., hematocrit 33 percent volume of packed cells and white blood cells 7,600, with anormal differential count. The anemia was thought to be dueto blood loss at the time of the accident. On admission theurine had a specific gravity of 1.006 and contained no sugaror albumin. The sediment showed red blood cells 1 to 2, whiteblood cells 1 to 2 and numerous hyaline casts. The Sulkowitchtest for hypercalcinuria was 4 plus. Chemical examination ofthe blood revealed a serum calcium level of 15 rag. per hundredcubic centimeters, serum phosphorus 3.8 mg. per hundredcubic centimeters, blood nonprotein nitrogen 52 mg. per hun¬dred cubic centimeters and serum carbon dioxide combiningpower 72.7 volumes per cent. Chart 1 illustrates the subsequentcourse of events.Course.—Fluids were forced and the patient was provided

with a low calcium diet (0.2 Gm. of calcium intake daily).Nausea, vomiting and abdominal pains disappeared on thesecond day and he remained symptom free thereafter.Attention is called to the prolonged elevation of the

blood calcium. It is interesting to note that there wasno concomitant depression of the blood phosphorus. Atransient degree of renal impairment accompanied thehypercalcemia. This was evidenced by the elevation ofthe blood nonprotein nitrogen and the depression of thephenolsulfonphthalein and urea clearances. We shouldlike to suggest, however, that this functional impair¬ment was not by any means entirely transient despitethe rapid return of the phenolsulfonphthalein and ureaclearance to normal values, for even after weeks had

From the Medical Clinic, the School of Medicine, Johns HopkinsUniversity and Hospital.

1. Reed, C. I., and Seed, L.: The Treatment of Clinical Tetany withIrradiated Ergosterol, Endocrinology 17: 136-148, 1933. Rappaport,B. Z., and Reed, C. I.: Viosterol of High Potency in Seasonal HayFever and Allergy, J. A. M. A. 101: 105-109 (July 8) 1933. Rappaport,B. Z.; Reed, C. I.; Hathaway, Milicent L., and Struck, H. C.: TheTreatment of Hay Fever and Asthma with Viosterol of High Potency,J. Allergy 5:541-553, 1934. Dreyer, I., and Reed, C. I.: The Treat-ment of Arthritis with Massive Doses of Vitamin D, Arch. Phys. Therapy16:537-540, 1935. Vrtiak, E. G., and Lang, R. S.: Observations onthe Treatment of Chronic Arthritis with Vitamin D, J. A. M. A. 106:1162-1163 (April 4) 1936. Vollmer, H.: Treatment of Rickets andTetany by Parenteral Administration of One Massive Dose of Vitamin D,J. Pediat. 16:419-432, 1940. Steinberg, C. L.: Massive Doses ofVitamin D in Chronic Arthritis: Its Effect on Calcium Metabolism,J. Lab. & Clin. Med. 24: 17-24, 1938.

2. Stacey, R. S.: Treatment of Low Calcium Tetany with Calciferol,Lancet 2:656-658, 1935. Ross, S. G., and Williams, W. E.: VitaminD Intoxication in Infancy, Am. J. Dis. Child. 58:1142 (Nov.) 1939.Klein, I. J.: Effects of Massive Doses of Irradiated Ergosterol, J. A.M. A. 92:621 (Feb. 23) 1929. Harris, L. J., and Moore, T.: Hyper-vitaminosis D and Vitamin Balance, Biochem. J. 22: 1461, 1928. Vrtiakand Lang.1 McLean.3 Abrams and Bauer.11

3. McLean, F. C.: Activated Sterols in the Treatment of ParathyroidInsufficiency, J. A. M. A. 117: 609-619 (Aug. 23) 1941.

4. Steinberg, C. L.: Massive Doses of Vitamin D in ChronicArthritis, J. Lab. & Clin. Med. 24: 17-24, 1938.

passed the patient still could not concentrate his urineabove 1.020. This we believe is evidence of continuedand significant renal damage. Throughout this entireperiod the daily urinary output was 1,200 to 2,000 cc.After the first five days the urinary sediment was

entirely clear. The blood pressure was never elevatedabove 120 systolic and 80 diastolic. The electrocardio¬gram remained normal. X-ray examination showed nocalcium in the kidneys or other tissues and no osteo¬porosis. Biopsy of the sternum on August 5 showednormal bone marrow. Six months after the accidentthe fracture had not yet healed and orthopedic con¬

sultants felt that there was delayed healing and poorcallus formation.Case 2.—History.—W. S., a Negro aged 22, was admitted

to the medical service of the Johns Hopkins Hospital on July 25,1941. His general health had been excellent and he had neverhad any serious illnesses. He did not have nocturia, hematuria,dysuria or frequency. On June 30 he was struck by an auto¬mobile and sustained a compound fracture of the left tibia andfibula and also of the lower end of the left femur. The legwas put in traction and a cast applied. On July 8 he wasstarted on approximately 750,000 international units daily ofa preparation of irradiated ergosterol containing 50 per centcalciferol and 50 per cent lumisterol, tachysterol and toxisterol.This preparation was frequently given in milk. On July 25he was taken with nausea and vomiting. The diagnosis ofirradiated ergosterol intoxication was suggested and he wasadmitted to the medical service at this time. Physical exami¬nation revealed no abnormalities other than the fractures. Onadmission examination showed red blood cells 4,800,000, hemo¬globin 12 Gm., hematocrit 35 per cent volume of packed cells,white blood cells 7,450. On admission the urine had a specificgravity of 1.005 and contained no sugar or albumin. There wasan occasional white blood cell and cast. There were no redblood cells. Chemical examination of the blood revealed a

serum calcium level of 18 mg. per hundred cubic centimeters,serum phosphorus 2.9 mg. per hundred cubic centimeters andblood nonprotein nitrogen 47 mg. per hundred cubic centimeters.Chart 2 illustrates the patient's subsequent course.

Course.—Fluids were forced and the patient was given adiet containing approximately 0.2 Gm. of calcium daily. Intwenty-four hours the nausea and vomiting subsided and heremained symptom free.

One is struck by the remarkably prolonged elevationof the serum calcium. As in the first case the phos¬phorus was not reduced in the presence of hypercalce-mia but remained at a normal or slightly elevated level.Azotemia was slight and of short duration. There wasalso a transient depression of the phenolsulfonphthaleinexcretion and urea clearances and a persistent inabilityof the kidnevs to concentrate urine. It is of interest

that on November 27 (twenty weeks following theadministration of the drug) the patient returned fora check-up. Although the phenolsulfonphthalein excre¬tion was 80 per cent and the urea clearance 120 percent of standard, he was unable to concentrate the urineabove 1.010. An interesting feature which this patient

showed was remarkable prolongation of the PR interval.This has been described in various conditions associatedwith hypercalcemia. X-ray studies did not show cal¬cification in the urinary tract or soft tissue. Therewas no osteoporosis. The patient is still in a castbecause of delayed healing.

COMMENTIn these two cases the administration of repeated

large doses of irradiated ergosterol was associated witha prolonged hypercalcemia and persistent impairmentof renal function.Although postmortem examination of rats, rabbits,

monkeys and dogs that had been given large amountsof vitamin D have shown renal damage of varyingdegrees,5 similar postmortem lesions have been describedin observations on only 3 patients, all infants, whohad been given comparable doses of the vitamin. Thesecases have been described in detail by Thatcher,6 Malm-berg T and Putscher.8 But we should not thereforeconclude that renal damage is a rare form of ergosterolintoxication. Let us but remember that polyuria andnocturia have been repeatedly mentioned by numerouswriters as being manifestations of vitamin D intoxica¬tion. Unfortunately, however, none of these clinicalinvestigators have reported studies of renal function.The question presents itself Why did these 2 patients

develop evidences of renal impairment? What par¬ticular circumstances may have led to it? At the veryoutset we should admit that it is perhaps impossibleto give a completely satisfactory answer. But at leastwe can surmise.Was it the total quantity of ergosterol which had been

given that was responsible ? This appears to be unlikely,since much larger doses have been given to otherpatients without any signs of intoxication. ThusVollmer9 gave 2,260,000 and 1,260,000 units of vita-

EB5B3 •-Activated Erflo»t«rol Preparotfon- 1.000,000 I.U. Vitamin 0 par cc.30-40 gits. p«r Doy

Chart 1.—Observations in case 1.

SO 69 65

3« »64*

2* 3* 3+ 3* 3+

Chart 2.—Observations in case 2.

5. Steck, Deutsch, Reed and Struck.10 Chown, Lee, Teal and Currie.17Ham.16

6. Thatcher, Lewis: Hypervitaminosis D with a Report of a FatalCase in a Child, Edinburgh M. J. 38:457, 1931.

7. Malmberg, N.: Acta. paediat. 8:364, 1928.8. Putscher, W.: Ztschr. f. Kinderh. 92:269, 1929.9. Vollmer, H.: Distribution of Vitamin D in the Brain After

Repeated Administration of Massive Doses, Arch. Pediat. 58:9, 1941.

min D3 respectively to 2 children who were about todie of a tuberculous infection, and nothing attributableto hypervitaminosis was found post mortem. Steck,Deutsch and Reed 10 have shown that 20,000 units perkilogram daily may be given to dogs or to patients forindefinite periods without evidences of intoxication.However, there is no unanimity of opinion on thisquestion. Bauer and Abrams ll reported that in aseries of patients which they studied the administrationof more than 200,000 units daily resulted in evidencesof intoxication of a more or less severe degree, amongthem being polyuria, polydipsia and nocturia. Therewould therefore appear to be factors other than dosageat play.

Bauer11 and others have called attention to thegreat individual variation from patient to patient inthe dose required to produce intoxication. An amountinsignificant to 1 patient may make another acutely ill.A seasonal variation with reactions much more fre¬quent in the summer time is well established.Diet is also an important factor, since the degree

of hypercalcemia produced by irradiated ergosterol is toan important extent conditioned by the amount ofcalcium ingested 12 and we feel strongly that the renaldamage is occasioned solely by the hypercalcemia.Not the least important point is the manner in which

the ergosterol is administered. Lewis 13 has demon¬strated that vitamin D or ergosterol given in milkhas ten times the potency of that given in oil. AndBauer u points out that the lack of toxicity reportedby some observers following the administration of largedoses of ergosterol may be accounted for on this basis.We should like to urge strongly that the fact that

these 2 young, vigorous men were immobilized incasts probably played a major role in facilitating thehypercalcemia ; for immobilization alone through atro¬phy of disuse, as emphasized by Albright,14 may producehypercalcemia with resultant renal damage in a youngactive person. When to the hypercalcemia so producedone adds the hypercalcémie effect of the irradiatedergosterol, an accumulation of factors can result whichmay prove extremely damaging to the kidneys whichhave to excrete it.We had, therefore, several factors at work in these

2 cases which we suggest played a part in producingthe clinical picture : large dosage of irradiated ergos¬terol, a diet of high calcium content, the administrationof irradiated ergosterol in milk, the administration ofirradiated ergosterol in summer time and finally immo¬bilization in casts. Which of these factors played themost important part in giving rise to the intoxicationseems a matter of debate.Having considered why the intoxication occurred in

these cases, one may next ponder over how it occurred.There are at present two schools of thought con¬

cerned with the mechanism of vitamin D or ergosterolintoxication. One holds that all the symptoms ofintoxication are due to hypercalcemia with consequentprecipitation of calcium salts in the various affected

tissues of the body. The other contends that hyper¬calcemia is not at all necessary and that injury andnecrosis of body tissues can occur in the completeabsence of hypercalcemia or of the deposition of calciumsalts. Reed15 has called attention to the fact thathypercalcemia of an extreme degree may occur in thecomplete absence of any evidence of intoxication. Con¬versely, he states that he has seen severe intoxicationeven to the lethal stage in the presence of a perfectlynormal serum calcium. Ham,16 on the other hand,in a series of experiments on rats demonstrated thatno degeneration of tissues preceded the precipitationof calcium salts and thought therefore that ergosterolhad no specific effect on the tissues but produced dam¬age solely through supersaturation of the blood serumwith calcium and consequent salt precipitation. Withample evidence to prove both suppositions, one is freeto choose sides.In these 2 cases we are particularly interested in

attempting to picture the nature of the lesions producedin the kidneys, for that is where the damage was done.The most striking functional abnormality which these 2patients evidenced was a persistent inability to con¬centrate their urine, and note that this functionalimpairment persisted in the presence of a normalphenolsulfonphthalein excretion andmrea clearance, andin the absence of albuminuria or hematuria. One wouldtherefore expect to find the chief anatomic alterationsin the renal tubules.

Is there any evidence to support this supposition ?In animal experiments Steck, Deutsch and Reed10found that the kidney was the organ which was mostvulnerable to ergosterol intoxication. These investi¬gators described renal injury as due to calcium deposi¬tion which began in the tubules and thence spreadto involve the entire kidney. Chown, Lee, Teal andCurrie17 in experiments on rabbits noted depositionof calcium within and without tubules with consequentobstruction, which finally resulted in atrophy of somenephrons and dilatation of others. They also notednecroses and inflammatory reaction which occurredabout the tubular concentrations. Thatcher ° describedthe pathologic findings in the kidneys of an 18 monthold infant who died following the administration oflarge amounts of viosterol. These consisted of calciumdeposits in the lumens of the collecting tubules withinflammatory reaction about them and fatty degenera¬tion in the cells of the convoluted tubules.It is our opinion that the primary pathologic agent

in these 2 cases was the hypercalcemia which per sedamaged the renal tubular epithelium, the only perma¬nent sequelae of this injury being an inability to con¬centrate urine. In a personal communication Longcopestates that he has seen exactly similar sequelae followingsulfonamide nephritis,18 a condition in which there isabundant evidence in both man and animals of exten¬sive tubular involvement.

10. Steck, I. E.; Deutsch, A. B.; Reed, C. I., and Struck, H. C.:Intoxication with Vitamin D, Ann. Int. Med. 10:951-963, 1937.11. Abrams, N. R., and Bauer, Walter: Treatment of RheumatoidArthritis with Large Doses of Vitamin D, J. A. M. A. 111: 1632-1638(Oct. 29) 1938.12. Bauer, W.; Marble, A., and Claflen, D.: Studies on the Mode of

Action of Irradiated Ergosterol: I-IV, J. Clin. Investigation 11:1-63,1932. McLean.313. Lewis, J. H.: Clinical Experience with Crystalline D: Influenceof Menstruum on Effectiveness of the Antirachitic Factor, J. Pediat. 6:362, 1935.14. Albright, Fuller; Burnett, C. H.; Cope, Oliver, and Parson,William: Acute Atrophy of Bone (Osteoporosis) Simulating Hyperpara-thyroidism, J. Clin. Endocrinol. 1:711, 1941.

15. Reed, C. I.; Struck, H. C., and Steck, E.: Vitamin D, Universityof Chicago Press, 1939.16. Ham, A. W.: Mechanism of Calcification in the Heart and Aortain Hypervitaminosis D, Arch. Path. 14:613 (Nov.) 1932.17. Chown, Bruce; Lee, Margaret; Teal, John, and Currie, Robert:Experimental Production of Nephritis in Rats by Means of ParathyroidHormone and of Vitamin D, J. Path. & Bact. 49:273-290, 1939.18. Antopol, William; Lehr, David; Churg, Jacob, and Sprinz, Hel-muth: Changes in the Urinary Tract and Other Organs After Admin-

istration of Three Sulfanilamide Derivatives, Arch. Path. 31: 592-602(May) 1941. Clemenko, D. R., and Wright, A. W.: Effects of Con-tinued Administration of Sulfathiazole and Sulfapyridine in Monkeys,ibid. 32:794-817 (Nov.) 1941. Gross, P., and Cooper, F.: UrolithiasisMedicamentosa, Urol. & Cutan. Rev. 44:4, 1940. Pepper, D. S., andHorack, H. M.: Crystalline Concretions in Renal Tubules FollowingSulfathiazole Therapy, Am. J. M. Sc. 199:674-679, 1940. Stryker,W. A.: Nature of Renal Lesion with Sulfapyridine Therapy, J. A. M. A.114:953-954 (March 16) 1940.

SUMMARY1. Two patients showed evidence of intoxication

which followed the administration of massive doses ofirradiated ergosterol.

2. The circumstances which may have contributedto this intoxication were the amount of drug whichwas given, the vehicle in which the drug was given,the calcium content of the diet, the factor of immobili¬zation and the season of the year.

3. Sudden skeletal immobilization through its effectin producing hypercalcemia in young and vigorouspersons undoubtedly played an important part in theintoxication.

4. Hypercalcemia alone appears responsible for therenal damage manifested by these patients.

5. Because of the type of functional impairmentshown by these patients, principal damage is thoughtto have occurred in the renal tubular epithelium.

6. The functional impairment found in certain casesof sulfonamide nephritis is similar.

7. Massive doses of irradiated ergosterol, at leastunder certain circumstances, present potential clanger.

THE EFFECT OF PREGNANCY ON THECOURSE OF MYASTHENIA GRAVIS

HENRY R. VIETS, M.D.ROBERT S. SCHWAB, M.D.

AND

MARY A. B. BRAZIER, Ph.D.BOSTON

Pregnancy may and often does cause profoundchanges in patients with myasthenia gravis. In someinstances during part or all of the nine months ofchildbearing symptoms disappear entirely; more rarelythe disease increases in severity in the early months,and in a few instances during this period abortions fortherapeutic reasons have been considered justifiable.More rarely remission does not take place during theentire pregnancy.The subject has received scant attention in the litera-

ture, and few instances of pregnancy occurring inpatients with myasthenia gravis have been reported.This is partly due to the rarity of the disease. At theBoston Lying-In Hospital only 1 patient with myas-thenia gravis was registered in more than 63,268 admis-sions between 1900 and 1940. Most textbooks on

obstetrics, moreover, do not mention the disease.Myasthenia gravis, or grave muscle weakness, is a

disease characterized by an abnormal state of fatigabilityof particular voluntary muscle groups. The diseasewas clearly described in the last two decades of thenineteenth century and widely recognized as a clinicalentity after 1900. The symptoms commonly observedin the order of their frequency, as pointed out by Vietsand Schwab,1 are ptosis of the eyelids, often with accom¬

panying diplopia ; dysphagia, dysarthria and weaknessof the muscles of the jaw ; general muscular involve¬ment and neck muscle fatigue. The progress of myas¬thenia gravis is characterized by spontaneous remissionsand relapses.

Myasthenia gravis, however, is much more commonthan was formerly thought. We have notes on 95patients in the records of the Myasthenia Gravis Clinicat the Massachusetts General Hospital observed since1935 ; more than 70 of them have come under directobservation by one of us (H. R. V.) either at theclinic or in private practice. Of this total, we havedata on 8 patients who have had one or more pregnan¬cies during the course of their illness; in 2 instancesdelivery took place while the patient was under ourcare. It is on this series of cases that we are reporting,first reviewing the previous literature.

REVIEW OF THE LITERATUREThat pregnancy might affect the disease was sug¬

gested by Sinkler 2 as early as 1899, when myastheniagravis was little known ; his patient improved duringher sixth pregnancy and had an easy labor, but symp¬toms developed again a few days after delivery. Thedisease was of seven years' duration, with three knownrelapses in its course. Punton 3 in 1899 reported an

example of the disease beginning shortly after a pro¬longed and difficult labor. In 1901, Burr andMcCarthy 4 described a patient with severe myastheniagravis, who at the end of three or four months of hersecond pregnancy died of respiratory paralysis. Thedisease had its onset about one and one-half years beforedeath.In 1902 Goldflam,5 who wrote one of the earliest

descriptions of myasthenia gravis, in 1893,6 continuedhis account of 1 of his patients, unmarried when firstobserved ten years before (5, p. 323, case III). Shewas married in 1897 and, by 1902, at the age of 32,had borne three children. For five years before hermarriage the disease had progressed by relapses andremissions. Her first child was born in January 1898,but her exact condition during the pregnancy is notknown. Goldflam implies that she was well, for hestates that three months after delivery symptomsreturned. After a relapse of two months she had asecond remission lasting two years. A second preg¬nancy, coming during this period, terminated normallyin May 1900. By implication, again it is presumed thatshe was well during her second pregnancy, since it isstated that she suffered a relapse a little more than threemonths after she was delivered, and by August 1900her condition was considered serious. In her thirdpregnancy her condition improved immediately. Atthe end of eight months she gave birth to a prematurechild who died. Three months later the symptomsof myasthenia gravis returned, although in a milderdegree. Goldflam was much impressed by the patient'sgood health during pregnancy and had a standingpleasantry with his patient: "You should always bepregnant to remain in continuous good health."The next report came from Kohn,7 whose patient

manifested symptoms of myasthenia shortly after herfourth pregnancy. By the end of the fourth month of

Aided by a grant from Hoffmann-LaRoche, Inc.From the Myasthenia Gravis Clinic, Massachusetts General Hospital.Read in part before the Boston Society of Psychiatry and Neurology,

Dec. 11, 1941.1. Viets, H. R., and Schwab, R. S.: The Diagnosis and Treatment

of Myasthenia Gravis, J. A. M. A. 113:559-562 (Aug. 12) 1939.

2. Sinkler, W.: Asthenic Bulbar Paralysis, J. Nerv. & Ment. Dis.26: 536-544, 1899.

3. Punton, J.: Asthenic Bulbar Palsy, with Report of a Case,J. Nerv. & Ment. Dis. 26: 545-553, 1899.

4. Burr, C. W., and McCarthy, D. J.: Asthenic Bulbar Palsy,Am. J. M. Sc. 121:46-52, 1901.

5. Goldflam, S.: Weiteres \l=u"\berdie asthenische L\l=a"\hmung,nebst einemObductionsbefund, Neurol. Centralbl. 21:97-107, 154-160, 208-214, 252\x=req-\258, 303-310, 347-353, 390-397, 447-452, 490-496, 1902.

6. Goldflam, S.: Ueber einen scheinbar heilbaren bulb\l=a"\rparalytischenSymptomemcomplex mit Betheiligung der Extremit\l=a"\ten,Deutsche Ztschr.f. Nervenh. 4:312-352, 1893.

7. Kohn, R.: Myasthenia gravis pseudoparalytica und Gravidit\l=a"\t,Prag. med. Wchnschr. 28:242-244, 1903.