560

histological lesion and clinical colitis. Perhaps it would be appropriate to classify patients with both toxin and toxigenic C. difficile in the stool but without histological lesions as having "difficult diarrhoea", but we are open to suggestions. a

General

Hospital, Birmingham B4 6NH

M. R. B. KEIGHLEY D. W. BURDON G. A. G. MOGG R. H. GEORGE J. ALEXANDER-WILLIAMS H. THOMPSON

DISAPPEARANCE OF FOCAL CRYPTOCOCCAL BRAIN LESION ON CHEMOTHERAPY ALONE

SIR,-Focal brain lesions and cerebral granulomas associated with central-nervous-system cryptococcis 1,2 are nothing like as common as cryptococcal meningitis.2,3 Cryptococcal meningitis can be successfully managed by chemotherapy alone, but no intracranial focal lesion associated with cryptococcosis has been reported to be cured in this way.3 Successful surgical excision, with or without subsequent chemotherapy, has been described but the mortality-rate may exceed 50% 1, 4-8. We have seen a patient with cryptococcal meningitis and an intracranial focal lesion detected by computerised axid tomography (C.A.T.). After treatment with amphotericin B without surgery the focal lesion disappeared. A 61-year-old male alcoholic was brought to the Wadsworth V.A. Hospital on June 2, 1976, semicomatose. His temperature was 39-4°C and he responded to noxious stimuli only. His neck was supple, and mild right-sided weakness more pronounced in the upper extremity was detected. Initial lumbar puncture was traumatic and showed normal pressure, 56 mg/ dl protein, 47 mg/dl glucose (serum-glucose 106 mg/dl) and one mononuclear cell/1. He subsequently had grand-mal seizures. Technetium pertechnetate brain scan was normal. Electroencephalogram showed only diffuse slowing of the brain-wave patterns. Indian-ink smear was negative, as were cerebrospinal fluid (c.s.F.) smear and culture for bacteria and mycobacteria. Fungal cultures of the C.S.F. grew Cryptococcus neoformans. C.S.F. cryptoccal antigen titre was positive at 1:128 by latex-agglutination test. (International Biological Laboratories, Rockville, Maryland.) His serum was positive for cryptococcal antigen but negative for antibody. On June 9, 1976, intravenous amphotericin B therapy was started in gradually increasing doses, with dramatic clinical improvement. Right homonymous hemianopsia was detected on Aug. 2, 1 month later this had resolved. Therapy was complicated by fever, chills, nausea, and vomiting during intravenous infusion, and by transient azotoemia, hypomagnesxmia, and hypocalcxmia, all of which resolved after completion of therapy. On June 21 his c.s.F. cryptococcal antigen titre dropped to 1:32, and subsequently to 1:8 and 1:4. Amphotericin B was continued until a total dose of 3 g was reached on Oct. 20. Simultaneous c.s.F. cryptococcal antigen titres done in the Veterans Administration Special Serology Reference Laboratory in Lexington, Kentucky, were negative by the microcomplement fixation method. By Oct. 12 c.s.F. cryptococcal antigen latex titres in our laboratory were still positive at 1:8d. Simultaneous c.s.F. latex agglutination antigen titres done by the Fungus Immunology Unit, Center 1. Selby, R. C., Lopez, N. M. J. Neurosurg. 1973, 38, 40. 2. Schroter, G. P., and others Surgery, 1976, 79, 268. 3 Bennett, J. E in Infectious Diseases (edited by P. D.

Hoeprich); p. Hagerstown, Maryland, 1952. 4. Brisman, R., Reid, R, Harrington, G. Surg. Neurol. 1973, 1, 43. 5. Roberts, M., Rinaudo, P. A., Tilton, R. C. J. Neurosurg. 1972, 37, 229. 6. 7. 8. 9

Department of Medicine, Wadsworth V.A. Hospital, and Department of Medicine, University of California, Los Angeles, Los Angeles, California, U.S.A. * Present address: Infectious Disease Division, Rancho Los

FRANCISCO L. SAPICO* Amigos Hospital, Downey, California

90242, U.S.A.

GAMMA-AMINOBUTYRIC ACID IN THE BRAIN IN SCHIZOPHRENIA

SiR,—There is general agreement that the activity of gluta-

decarboxylase (G.A.D.), the enzyme that catalyses the synthesis of Y-aminobutyric acid (G.A.B.A.), is normal in the postmortem brains of schizophrenics.’ Nevertheless, Dr Perry and colleagues (Feb. 3, p. 237) found significant reductions of G.A.B.A. concentrations in the thalamus and nucleus accumbens of post-mortem brains from schizophrenics. We here report normal concentrations of G.A.B.A. in both the thalamus and nucleus accumbens in brains of schizophrenics.

mate

1. Cross, A.

J., Owen, F. Biochem. Soc. Trans. (in the press).

945.

Liu, C. T. ibid. 1953, 10, 686. Ching, A. D., Wolf, S. M., Ruskin, J. Calif. Med. 1973, 119, 59. Vijayan, N., Bhatt, G. P., Dreyfus, P M. Neurology, 1971, 21, 728. Twigg, H. L., Axelbaum, S P., Schellinger, D. J. Am. med. Ass. 1975, 234, 314.

for Disease Control, Atlanta, were negative. On Dec. 2, 1976, and Jan. 28 and March 24, 1977, follow-up C.S.F. antigen titres dropped to 1:2 (our laboratory) and were again negative in the c.D.c. and Lexington laboratories. A computerised axial tomogram (C.A.T.) on July 29, 1976, showed a definite area of increased density in the left parasagittal-occipital region; on Oct. 7 the lesions had disappeared. In this patient, presenting with localising neurological signs and a corresponding area of increased density on C.A.T. brain, the focal lesion completely resolved over a span of 22 months and during intensive intravenous amphotericin B therapy, and the right homonymous hemianopsia disappeared. Perhaps smaller focal lesions associated with cerebral cryptococcosis may be responsive to chemotherapy alone, while the larger lesions detected by radionucleide scans and/or angiography require surgery.

Fig. 1-G.A.B.A. concentrations in nucleus accumbens and thalamus of controls (8) and schizophrenics (0). Mean values (±S.E.) in the accumbens and thalamus of controls were 53.2±3.6 (n=19) and 20.4+1.4 (n=13), respectively, and 56.5±3.1(n=19) and 23.9::t 1.6 (n=9) for schizophrenics.

561 to be reduced. However, c.s.F. concentrations of have been reported to be normal in schizophrenia. 12 On the basis of the above results it seems that a G.A.B.A. deficiency in brains from schizophrenics is unlikely to be a general

workers" G.A.B.A.

finding. J. CROSS T. J. CROW A.

Division of Psychiatry, Clinical Research Centre, Harrow, Middlesex HA1 3UJ

F. OWEN

ALPHA1-ANTITRYPSIN PHENOTYPES IN PARAPROTEINÆMIAS

SiR,—o-antitrypsin (

Gamma-aminobutyric acid in the brain in schizophrenia.

560 histological lesion and clinical colitis. Perhaps it would be appropriate to classify patients with both toxin and toxigenic C. difficile in the...
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