828

However, Dr S. Villani and Dr W. D. Weitzel have lately toldus of a case of mania secondary to Graves’ disease in a 43-year-old woman with no personal or family history of affective dis-order. This case meets all our criteria for secondary mania andprovides an example of yet another category of secondarymania-those with an endocrinologicat cause. Now that

secondary mania has been given some legitimacy we expectthat more cases of this and other types will be found, addingdata for further theoretical and experimental explorations ofthe causes of mania.

Alcohol, Drug Abuse,and Mental Health Administration,

Rockville, Maryland 20852, U.S.A.CHARLES KRAUTHAMMERGERALD L. KLERMAN

CREUTZFELDT-JAKOB DISEASE AND FERRETS

SiR,—Creutzfeldt-Jakob disease (C.J.D.) is transmissible toanimals in the laboratory,’ and accidental human transmissionis possible.2,3 Kuru, with similar properties in the laboratory,is thought to have been transmitted naturally by cannibalism.4In an attempt to link C.J.D. with transmissible scrapie, sug-gested methods of natural transmission of C.J.D., if indeed thisoccurs, have included the eating of sheep’s eyeballs5 or brain.6It is difficult to conceive that such a rare disease as C.J.D.could be maintained solely by case-to-case transmission, andsome reservoir of infection, human or animal, is probable. Ina study of the epidemiology of the disease’ a tenuous associ-ation with the keeping of ferrets was reported and is here de-scribed in further detail.A 63-year-old man died in August, 1973, of histologically

proven C.J.D. after a 6-month history of typical symptoms. Hehad kept ferrets until 1939. In mid-1971 he had found a ferretin the hedge. It bit him on the thumb but he took it home asa pet. After the patient’s death the animal, which appearedhealthy, was killed. At necropsy the brain and thoracic and ab-dominal organs were macroscopically normal. Histologically,minor chronic lymphocytic infiltration was seen around theportal tracts of the liver and around a cystic lesion in the renalcortex. Coronal sections of the brain showed a normal cere-brum and brainstem. In the cerebellar white-matter there wasa lymphocytic infiltration around several capillaries and

thickly around a leptomeningeal vein. No spongiform changeswere seen. Frozen brain was sent to the National Institutes ofHealth and inoculated into four different species of monkeyand one cat. The surviving animals have remained symptom-free, and no evidence of spongiform encephalopathy was foundin two animals that died (C. J. Gibbs, Jr, personal communica-tion).Of 41 further patients with necropsy-proven C.J.D. in

whom the information is available, 2 have kept ferrets. Onewoman, a patient of Dr J. N. Milnes, died in 1971. Her hus-band had kept ferrets from 1943 to 1956 and again from 1960to 1965. He could not recall that his wife had ever been bitten

by a ferret, and her chief contact with the animals was thatof washing their food dishes.A man of 67 died of proven C.J.D. in 1975. As a young man

he had used ferrets for rabbiting and he had also kept ferretsfrom 1950 to 1955. His wife could not recall his being badlybitten, but slight nips were commonplace.

1 Gibbs, C. J., Gajdusek, D. C., Asher, D. M., Alpers, M.-P., Beck, E., Daniel,P. M., Matthews, W. B. Science, 1968, 161, 388.

2. Duffy, P., Wolf, J., Collins, G., DeVoe, A. G., Streeter, B. New Engl. J. Med.1974, 290, 692.

3. Bernoulli, C., Siegfried, J., Baumgartner, G., Regli, F., Rabinowitz, T., Gaj-dusek, D. C., Gibbs, C. J. Lancet, 1977, i, 478.

4 Gajdusek, D C. in Tropical Neurology (edited by J. D. Spillane). London,1973.

5 Herzberg, L., Herzberg, B. N., Gibbs, C. J., Sullivan, W., Amix, H., Gaj-dusek, D. C. Science, 1974, 186, 848.

6. Alter, M , Frank, Y., Doyne, H., Webster, D. D. New Engl. J. Med. 1975,292, 927

7 Matthews, W. B J. Neurol. Neurosurg Psychiat. 1975, 38, 210.

A further case where no necropsy was done was probably anexample of C.J.D. A man of 61 was admitted as an emergencyfollowing the acute onset of confusion. It was thought thatsome rigidity of the limbs had been present for 12 months andthat mental function had declined for 3 months before admis-sion. His rigidity improved temporarily with levodopa but hebecame increasingly demented. Occasional myoclonusoccurred in the limbs. The c.s.F. was normal. The E.E.G. (DrElman Poole) contained bilateral recurrent triphasic sharp ele-ments. He died 3 months after admission. He had kept ferretsfor many years and would allow his favourite animal to runaround inside his shirt, but he had disposed of them some 10years before bis death.A retrospective case-control study of the prevalence of ferret

keeping in a comparable population is clearly impracticableand the significance of these observations can only be conjec-tural. The prolonged interval between the last contact withferrets and the onset of symptoms cannot be regarded asexcluding the animals as a source of infection because newcases of kuru are still occurring, with greatly reduced inci-dence, even though cannibalism, the apparent source of infec-tion, was abolished some 20 years ago. Spongiform encephalo-patby is not known to occur spontaneously in ferrets althougha form does affect domestic mink (transmissible mink encepha-lopathy). As with other suggested antecedents, however, it is

equally plain that most patients with C.J.D. have not beenexposed to ferrets, but this would not exclude their possiblerole as a reservoir of infection.

Department of Clinical Neurology,University of Oxford,Churchill Hospital,Oxford OX3 7LJ

W. B. MATTHEWSM. CAMPBELLJ. T. HUGHESA. H. TOMLINSON

LIFE WITH A SPLIT BRAIN

SIR,-In your editorial of March 3 you may have misledyour readers about the consequences of corpus-callosum sec-tion for epilepsy. As you correctly note, Bogen and Vogel’ didcomplete commissurectomies, which include division of all pos-terior commissures such as the splenium, psaltrum, habenular,and posterior commisures. You then imply that Gazzaniga andWilson’s patients underwent similar operations with similarlystriking split-brain functioning and handicaps.2’ However,Gazzaniga and Wilson found preservation of significant cross-over function in some patients thought to be totally disconnec-ted ; additional patients underwent a section of the corpus cal-losum only, with excellent preservation of cross-over functionsbetween hemispheres. Shucart and Stein’ have reported a

series of patients undergoing mid and anterior corpus-callosumsection, without identifying split-brain complications.

Over the past four years, I have operated on nine patientsfor benign and invasive tumours in the posterior third ven-tricle ; four of these patients were neurologically normal beforesurgery and were old enough to be tested preoperatively forvisual, tactile, and verbal memory cross-over functions. All pa-tients were tested postoperatively and were found to be with-out even "subclinical" defects from their mid and anterior cor-pus-callosum section. Such anterior and mid-callosal sectionsfor tumour or seizure do not themselves produce the split-brainconditions you refer to, and patients should not be denied thebenefit of tumour biopsy (removal in three cases) or seizurecontrol3 on this basis.

Division of Neurosurgery,Loyola University Medical Center,Maywood, Illinois 60153, U.S.A. TIMOTHY B. SCARFF

1. Bogen, J. E., Vogel, P. J. in Les sydromes de disconnexion calleuse chezl’homme (edited by F. Michel and B. Schott). Lyon, 1975

2. Gazzaniga, M. S., and others Neurology, 1975, 25, 10.3. Wilson, D. H., and others ibid. 1978, 28, 649.4. Shucart, W. A., Stein, B. M. Neurosurgery, 1978, 3, 339.