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In the present case the patient was exposed apparentlyto a total of only 2-3 g. in the course of a month, and acuteillness ’was present six weeks after the start of therapy.Although there was no history of a prodromal phaseresembling acute rheumatoid arthritis, the patient com-plained of pains in his legs and may have had arthritis.’Despite these differences the similarity of the presentcase to others previously reported is outstanding. Rapidrecovery followed withdrawal of the hydrallazine and wefeel convinced that the patient’s illness was due to

hydrallazine.Despite serious toxic effects in 7-9% of patients treated

with hydrallazine American workers with wide experienceof it (Schroeder and Morrow 1953, Dustan et al. 1954,Perry and Schroeder 1954) regard it as a valuable thera-peutic agent for which no adequate substitute is available,and are of the opinion that its use must constitute acalculated risk, which is justifiable in severe and malig-nant hypertension. We feel that the hazards involvedmay not be sufficiently well known in this country.

SummaryA case of acute pyrexial illness and pancytopenia

occurring during hydrallazine therapy for hypertensionis reported.Our thanks are due to Dr. D. K. Adams and Dr. C. D.

Anderson for their interest in this case.

REFERENCES

Dustan, H. P., Taylor, R. D., Corcoran, A. C., Page, I. H. (1954)J. Amer. med. Ass. 154, 23.

Goodman, L. S., Gilman, A. (1955) The Pharmacological Basis ofTherapeutics. 2nd ed., New York.

Harris, E., Turner, R. (1954) Lancet, i, 429.Kaufman, M. (1953) J. Amer. med. Ass. 151, 1488.Khan, M. A. (1953) Brit. med. J. i, 27.Morrow, J. D., Schroeder, H. A., Perry, H. M. jun. (1953) Circula-tion, 8, 829.Perry, H. M. jun., Schroeder, H. A. (1954) J. Amer. med. Ass. 154,

670.Schroeder, H. A. (1954) Practitioner, 173, 195.- Morrow, J. D. (1953) Med. Clin. N. Amer. 37, 991.

AN UNUSUAL CASE OF TUBEROUS

SCLEROSIS

SAMIR K. GUPTAM.B. Calcutta

LATE SENIOR HOUSE-OFFICER, NORTH MIDDLESEX HOSPITAL,LONDON

THOUGH the term tuberous sclerosis refers really tochanges in the brain it has come to signify, in its classicalform, a familial disease of children with mental deficiency,epilepsy, and adenoma sebaceum of the face as its mostcommon manifestations (Oswald 1952). This syndrome isalso called Bourneville’s disease, Pringle’s disease, andepiloia (a term coined by Sherlock in 1911 but now indisuse).The case described below is reported because of the

very late occurrence of epilepsy, the minimal mentaldeficiency, and the survival into the sixth decade.

Case-reportAn engineer, aged 51, was admitted to hospital on June

18, 1956, with active pulmonary tuberculosis.On admission he had adenoma sebaceum (fig. 1) and multiple

subungual fibromata in hands and feet (fig. 2), and multipleskin tags and a few villous papillomata elsewhere. Treatmentwith streptomycin, p-aminosalicylic acid, and isoniazid in theusual daily dosage was begun.Convulsion.-Suddenly on July 24, 1956, for the first time

in his life he had an epileptiform convulsion without an aura.Facial twitching was rapidly followed by generalised tonicspasm, cyanosis, stertorous breathing, coma, and incontinenceof urine. No cardiovascular abnormalities or localisingneurological signs were elicited, but both plantar responseswere extensor. In about ten minutes he regained consciousnessbut remained confused for another twenty minutes ; hisplantar reflexes were now flexor.

Family History.-Further inquiry revealed that his youngerson, aged 23, had adenoma sebaceum, and recurrent attacksof epilepsy and was mentally defective. The family historywas otherwise irrelevant.

Investigations.-The erythrocyte-sedimentation rate was

47 mm. in the first hour (Westergren). Haemoglobin 90%(13-3 g. per 100 ml.). White cells 10,100 per c.mm. (differentialcount normal). Wassermann reaction and Kahn test negative.Sputum contained acid-fast bacilli in smear and on culture.Radiography of the skull showed scattered. calcification in thepineal body, the choroid plexus, and the pituitary fossa;areas of erosion in the inner table of the vault ; and a fewdiscrete " punched-out " areas. The whole picture was

consistent with the diagnosis of tuberous sclerosis. Radio-graphs of thehands andlong boneswere normal.Plain radio-

graphs and

tomograph ofthe chestshowed ex-tensive pul-monary tub-erculosis (nohoneycombappearance).Excretionurographyshowed noevidence ofrenal tumour.Retinoscopyshowed, inthe left eye,a glisteningwhite nodularmass slightlybigger thanthe disc andprojecting onthe nerve-ending, ,suggestingeither tuber-ous sclerosis or a gigantic collection of colloid degeneration.The psychiatrist’s opinion was that the patient’s intelligencewas slightly subnormal but did not amount to mental defi-ciency. Electro-encephalography showed mild non-specificabnormal theta activity with no definite evidence of epilepsyor of any local cortical lesion. Electrocardiography andlaryngoscopy gave normal results.

Fig. I-Adenoma sebaceum.

’Discussion

Tuberous sclerosis is a rare congenital disorder of bothectoderm and mesodermal elements. The incidence hasbeen estimated at about 1 in 300,000 in London (Dawson1954), divided probably equally between the milder andincomplete forms (formes frustes) and the classical forms.Half of the patients have a familial incidence, and manysuch families have been described (Dickerson 1951,

Fig. 2-Subungual fibromata.

1290

Dawson 1954, Jordan 1956). The pattern of inheritanceis probably through a dominant gene (Penrose 1938).

Medical consultation is sought by parents because ofrepeated seizures, mental retardation, or (rarely) adenomasebaceum. Patients with the classical triad rarely survivebeyond the age of 20. Nevertheless some patients reachthe third and fourth decades (Brain 1951). The prognosisis better in formes frustes, especially when adenomasebaceum alone is present (Wilson 1954). Stewart (1935).recorded the sudden death of an apparently normalyoung woman who did not even display adenomasebaceum, but necropsy disclosed characteristic cerebralchanges. Warrack (1950) described a case in a young manof normal intelligence who had fits just before his death. o

Conversely and exceptionally, patients in whom the fitshave come on early have lived to the age of 47 and 75(Lind and Nieuwenhuyse cited by Wilson 1954).The present case was a forme fruste until the epilepti-

form convulsion, coupled with slight but definite mentaldeficiency, clearly pointed to tuberous sclerosis. The ageof onset of fits merits further consideration. It is generallyagreed that the earlier the onset of fits the graver is theprognosis. It may be significant that, in the two casespublished by Stewart (1935) and Warrack (1950), thelate onset of fits was followed rapidly by death. The

unique feature of the present case is the appearance ofthe first and only fit at the age of 51. The patient hassince remained well. The cause of such a late fit isobscure. One interesting suggestion is the possibility ofmalignant change in the sclerotic glial tissues (Globuset al. 1932), of which there appears to have been norecorded instance ; nor is there any evidence of it in thepresent case.Adenoma sebaceum is usually symptomless ; it may

appear early or during adolescence. Subungual fibromata,usually multiple, emerge from the margin of the nail-bedto lie on the nail (fig. 2). The nail-plates show verticalridges and dystrophy (Sequeira et al. 1947). In additionto haemangiomatous plaques, warty growths or fibrousnodules may be found and verified by biopsy.

Radiography of the skull usually shows scattered areasof calcification and sclerotic plaques. Erosion of thevault and a cystic punched-out appearance in the

spongiosa are uncommon (Pancoast et al. 1942) but wereseen in the present case. Radiography of the hands andthe long bones may show cystic spaces. Plain radio-

graphy and tomography of the chest will detect anycystic change in the lungs. Kidney tumours may bedetected by excretion urography. Retinoscopy maydisclose phakomas (small lentil-shaped tumours), andlaryngoscopy may reveal a laryngeal tumour. Electro-

cardiography rarely shows heart-block. Electro-enceph-alography is of no particular value in diagnosing cerebraltuberous sclerosis (Dawson 1954).

SummaryA man, aged 51, who had tuberous sclerosis presented

with the syndrome of very late epilepsy, minimal mentaldeficiency, and survival into the sixth decade, in additionto retinal changes, subungual fibromata, dystrophy of thenails, and supporting radiological appearances of hisskull.The fact that he also had pulmonary tuberculosis is

regarded as fortuitous.I wish to thank Dr. Vernon Davies for permission to

publish ; Dr. R. J. Calvert and Dr. R. S. Francis for helpfulcriticism ; and Dr. J. E. Glancy for his electrocardiographicreport.

REFERENCES

Brain, W. R. (1951) In Horder, Lord. British Encyclopædia of MedicalPractice. 2nd ed., London ; vol. v, p. 266.

Dawson, J. (1954) Quart. J. Med. 23, 113.Dickerson, W. W. (1951) Arch. Neurol. Psychiat., Chicago, 65, 683.

References continued at foot of next column

Globus, J. H., Strauss, I., Selinsky, H. (1932) Z. ges. Neurol. Psychiat.140, 1.

Jordan, W. M. (1956) Brit. med. J. ii, 132.Oswald, N. (1952) In Marshall, G., Perry, K. M. A. Diseases of the

Chest. London ; vol. 11, p. 201.Pancoast, H. K., Pendergrass, E. P., Schaeffer, J. P. (1942) The Head

and Neck in Roentgen Diagnosis. 2nd ed., London; p. 663.Penrose, L. S. (1938) Spec. Rep. Ser. med. Res. Coun., Lond. no. 229.Sequeira, J. H., Ingram, J. T., Brain, R. T. (1947) Diseases of the

Skin. 5th ed., London ; p. 62.Stewart, R. M. (1935) Brit. med. J. ii, 60.Warrack, A. J. N. (1950) Ibid, ii, 1367.Wilson, S. A. K. (1954) Neurology. 2nd ed., London; vol. ii, p. 1031.

PARALYTIC ILEUS COMPLICATING

MESENCEPHALITIS

W. H. MOFFATTM.B. Belf., M.R.C.P.I.

FORMER SENIOR HOUSE-OFFICER

IN MEDICINE

A. P. GRANTM.D. Belf., F.R.C.P.I.,

M.R.C.P.ASSISTANT PHYSICIAN

BELFAST CITY HOSPITAL

TiiE association of true gastric and intestinal atonywith a lesion in the brain-stem appears to be either

excessively rare or seldom reported. We report a casein which bilateral involvement of the vagal nuclei

resulting from mesencephalitis was accompanied byparalytic ileus and the distribution of the causal virallesion was unusual.

Case-reportA male diabetic, aged 49, was admitted to hospital on

Feb. 6, 1955, with severe vomiting. His occupation as secretaryto the Master Butchers Association entailed frequent visitsto the local abattoir. His diabetes, which was of some years’standing, had been well controlled, and he had led an energeticlife. His illness began on Jan. 24, 1955, with pyrexia, whichlasted until Jan. 28. During this time he had an influenza-like illness with pyrexia, rigors, malaise, and unproductivecough without obvious physical signs in the chest. FromJan. 29 to Jan. 31 he was apyrexial and felt well apart fromthe cough. On Jan. 31 he had a severe paroxysm of coughingand temporary slurring of speech, which cleared up withintwo hours. On Feb. 1 he developed severe occipital headachewith neck stiffness, felt dizzy, and began to vomit. The neckstiffness lasted three days, and the headache graduallydiminished in intensity and cleared up in five days. Hisvomiting persisted and eventually became " coffee-grounds " ;it was not accompanied by abdominal pain. Since he could notkeep to a diet, and his diabetic state was becoming unstable,he was admitted to hospital on Feb. 6, 1955.Exam inationOn admission he was heavily built, plethoric and drowsy,

but well oriented, cooperative, and apyrexial, with pulse-rate70 and blood-pressure 150/90 mm. Hg. He vomited frequentlybut had no pain. His abdomen was not distended, but thebowel sounds were faint. Examination of his central nervoussystem revealed unequal pupils, the right being larger thanthe left ; slow rolling nystagmus to the right; weaknessof the left external rectus, with mild diplopia on lookingto the left ; and slight early weakness of the left side of hisface and tongue.InvestigationsThe cerebrospinal fluid (c.s.F.) was under normal pressure

and, apart from an increased amount of sugar (133 mg. per100 ml.), of normal constitution. Examination of the bloodshowed blood-sugar levels of 176-240 mg. per 100 ml.;white cells 16,900 per c.mm. (polymorphs 68%) ; and blood-urea and serum-bilirubin levels normal. The Wassermanreactions of both blood and c.s.F. were negative. The vomitusreacted strongly to tests for blood. The serum-sodium levelwas slightly lowered to 129 m.eq. per litre, but the serum-potassium and serum-chloride levels and the CO2-combiningpower of the blood were normal.

ProgressOn Feb. 7 the patient continued to regurgitate brown

fluid, and severe hiccup became distressing. He was treatedby intermittent gastric- suction, and all fluids were givenintravenously. Bowel sounds were still faint and infrequent.Palatal movements became weak.On Feb. 8-10 a sharp spiky pyrexia developed (101·4°F).

Complete paralytic ileus was now evident with abdominal