Journal of

J. Neurol. 221, 163--167 (1979)

Neurology © by Springer-Verlag 1979

Partial Kliiver-Bucy Syndrome Following Probable Herpes Simplex Encephalitis H. Shoji l, H. Teramoto 2, S. Satowa 3, H. Satowa 4, and Y. Narita 4 1.2Departments of Neurology and Psychiatry, Tokyo Metropolitan Hospital of Fuchu, 3Department of Internal Medicine, Tokyo Metropolitan Hospital of Okubo, 4Department of Psychiatry, The 2nd Tokyo National Hospital, Tokyo

Summary. An autopsy case of probable herpes simplex encephalitis (HSE) showed the partial Kltiver-Bucy syndrome from 1 to 7 months after the onset, which consists of strong oral tendencies, emotional changes and possible hypersexuality. Several cases of the syndrome in definite or probable HSE were reviewed in this paper. In these cases including our case, the partial or complete KltiverBucy syndrome has appeared from some interval (2 w e e k s - 1 month) after the acute phase, so that the syndrome should be noticed in survived or prolonged cases of HSE, as significant clinical symptoms suggesting bilateral involvement of the temporal lobes and limbic areas. Key words: Klt~ver-Bucy Syndrome - Encephalitis - Herpes simplex encephalitis - Herpes virus infections.

Zusammenfassung. Ein Autopsiefall von wahrscheinlicher Herpes-simplexEncephalitis (HSE) zeigte ein partielles Kltiver-Bucy-Syndrom vom 1. bis 7. Monat nach dem Anfang, das aus starken oralen Tendenzen, Ver~inderung e n d e r Emotionen und VerstS.rkung der sexuellen Aktivit/it bestand. Einige F~ille des Syndroms bei definitiv oder wahrscheinlicher HSE in der Literatur wurden diskutiert. In diesen F~illen einschlieglich unseres Falles ist das Kliaver-Bucy-Syndrom nach einem Intervall (2 W o c h e n - 2 Monate) nach der akuten Phase entstanden, so dag auf das Syndrom bei tiberlebten oder prolongierten Ffillen mit HSE als signifikante klinische Symptome geachtet werden sollte, das bilateralen Befall der Temporallappen und der limbischen Areale nahelegt.

The Kltiver-Bucy syndrome [8,9] is characterized by psychic blindness, oral tendencies, hypermetamorphosis, emotional changes and hypersexuatity. The syndrome was originally established in rhesus monkeys after the removal of both Address for offprint requests: Dr. H. Shoji, First Department of Internal Medicine, Kurume

University School of Medicine, Asahicho 67, Kurume-city, 830 Fukuoka, Japan

0340-5354/79/0221/0163/$ 01.00

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t e m p o r a l lobes, i n c l u d i n g the u n c u s a n d h i p p o c a m p u s . L a t e r , the p a r t i a l o r c o m p l e t e s y n d r o m e was o b s e r v e d in m a n [11, 14]. It is well k n o w n t h a t h e r p e s s i m p l e x v i r u s (type 1, H S V ) has a p a r t i c u l a r a f f i n i t y f o r the t e m p o r a l l o b e s a n d l i m b i c regions. T h e r e f o r e , it seems likely t h a t the s y n d r o m e can o c c u r w i t h h u m a n H S E . B u t u n i l a t e r a l i n v o l v e m e n t o f the t e m p o r a l l o b e s has b e e n e m p h a s i z e d f r o m the clinical a n d p a t h o l o g i c a l studies o f H S E [2, 3, 6, 12]. T h e p u r p o s e o f this p a p e r is to p r e s e n t a case o f p a r t i a l K l ü v e r - B u c y s y n d r o m e f o l l o w i n g p r o b a b l e H S E , in w h i c h b i l a t e r a l c h a n g e s o f the t e m p o r a l l o b e s a n d l i m b i c a r e a s w e r e f o u n d at the p o s t m o r t e m e x a m i n a t i o n .

Case Report The patient, a 24-year-old male, complained of headache on 6June 1974. The next day he had a fever of 39°C. Three days later he became delirious and was admitted to a hospital. Then, he had generalized convulsive seizures. On 17 June he was transferred to the Tokyo Metropolitan Hospital of Okubo. The past history and family history were noncontributory. On admission, the blood pressure was 120/50, the pulse rate 150/min, and the temperature 40°C. No herpetic cutaneous lesions were observed. He was semicomatose. There was moderate nuchal rigidity and Kernig's sign. Deep tendon reflexes were absent. Laboratory data: ESR was 51 mm/h; urinalysis normal; red blood cells 483 x 10 4, white blood cells 16,500 with 17% stab form, 73% neutrophils and 10% lymphocytes. Urea N 27 mg/100cm 3, s-GOT 49u, s-GPT 47u, LDH 1170u. The CSF pressure was 250 mm, the fluid containing 247 mononuclear cells and 38 red blood cells/mm 3, protein 45 mg/100 cm 3 and glucose 79 mg. The serum complement fixation (CF) titers to HSV during 12 days to 1 month after the onset were from 128 x to 512 x, and the CSF titer on the 18th day and 1 month after the onset was 32 x (Table 1). Virus isolation test from the CSF was negative. The serum CF titers to other viral antigens including Japanese encephalitis, measles, mumps and adeno virus were under 4x. Clinical Course. The patient was treated with antibiotics, prednisolone and cytosine arabinoside. At the beginning of July, he became afebrile and responsive. Laboratory data improved too. The following symptoms became apparent during July to August; first strong oral tendencies were observed. When pencil, tobacco, glasses, and other objects were given, the patient put them to his mouth and bit them (Fig. 1). Changes in diet were recognized. He ate temporarily large amounts. Secondly he was somewhat restless. In addition, emotional behavior toward the doctors and other persons including his family was markedly decreased, and he often exhibited negative responses to our questions. Thirdly the patient acted erotically toward the nUrses, though this was temporary. When they counted his pulse, the patient tried to touch the nurses on the thigh. Next, stereotyped behavior was observed. For example, he wrote his name or the same number repeatedly when he was ordered to write his name or make simple calculations. As other residua, he had dementia, possible motor aphasia and moderate spasticity in the lower extremities. In September, the patient was transferred to the Dept. of Psychiatry in

Table 1. CF titer to HSV After the onset

Serum CSF

12 days

18 days

1 month

128 x

512 x

256 x

32x

32x

2 months

16×

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Fig. 1. Oral tendency

Fig. 2. Cystic and necrotic lesions of bilateral temporal lobes including the limbic areas

the 2nd Tokyo National Hospital. His oral tendencies, emotional changes and stereotyped behavior continued, and he died of pneumonia on 2 February 1975. At the postmortem examination the unfixed brain weighed 1280g. Bilateral atropby of temporal lobes, left more than right, was observed. There was slight cloudiness of the leptomeninges over the convexities. On coronal sections of the brain, both temporal lobes including the limbic areas were replaced by cystic and necrotic lesions (Fig. 2). Microscopically, necrotic foci were seen in symmetrical areas of both temporal lobes, uncus, hippocampus, parahippo-

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campus, cingulate gyri, amygdala and insular gyri. The necrosis involved the left rectal gyrus, left claustrum and left Heschl gyrus. The nerve cells of the cortex in the necrotic foci were almost completely replaced by numerous fat-laden microglial cells, with reactive increase of enlarged astrocytes. Perivascular cuffing was scarcely observed in the necrotic regions and surroundings. Inclusion bodies of Cowdry type A were not found. There were no necrotic foci or inflammatory findings in the basal ganglia and other areas. Diseussion Klüver and Bucy [8,9] described the following peculiar symptoms in rhesus monkeys after the removal of both temporal lobes including the uncus and hippocampus: 1) psychic blindness, 2) oral tendencies, 3)hypermetamorphosis, 4) emotional changes, 5) changes in sexual behavior. The syndrome in man has been observed following bilateral temporal lobectomy, with Alzheimer's disease and with viral encephalitis [11, 14]. A m o n g the viral encephalitides, it seems likely that the syndrome can appear with HSE, because of a particular affinity of HSV (type 1) for the temporal lobes and limbic regions. However, there have been only a few cases of the partial or complete Klüver-Bucy syndrome seen with definite of probable HSE. In the series of HSE described by Oxbury and MacCallum [10], Cases 1 and 3 had strong oral tendencies. The necropsy examination in these cases revealed bilateral destruction of the temporal lobes, orbitofrontal lobes and cingulate gyri. In our prex/ious series [13], survival Case 2 had oral tendencies with a Korsakow syndrome and personality changes following the acute phase. The serum CF titer to HSV was 256 ×, and the CSF titer 32 ×. A survival case presented by Wallack and Hill [15] was a 31-year-old male who had hyposexuality, bulimia with memory disturbance after encephalitis. In this case, there were a fourfold increase (8 x to 32 ×) of the serum titer. Hiyamuta [5] reported an autopsy case of a 40year-old male who had oral tendencies, hypermetamorphosis, emotional changes and hypersexuality with memory disturbance from about 1 month to 3 years after the onset. The serum CF titer to HSV was 128 x during the convalescent phase. At the postmortem examination there were necrotic foci in both temporal lobes, both hippocampi and the right cingulate gyrus. Our present case developed the partial Klüver-Bucy syndrome from 1 to 7 months after the onset, with strong oral tendencies, emotional changes and possible hypersexuality. The autopsy examination also revealed necrotic lesions in both temporal lobes, uncus, hippocampus, amygdala and cingulate gyri. H a r a et al. [4] described the complete Klüver-Bucy syndrome from about 2 weeks to 2 months after the onset in an autopsy case of acute necrotizing encephalitis. At the necropsy examination, there were necrotic foci in both temporal lobes including the limbic areas. In this case, inclusion bodies of Cowdry type A were found. Akai et al. [1] reported a case similar to the one of H a r a et al. [4]. In the cases reviewed, the diagnosis was not confirmed by virus isolation from brain biopsy, except for the cases of Oxbury and MacCallum [10]. But these cases could be presumed to be probable HSE from the combination of the clinical features and serological diagnosis or the characteristic distribution of the necrosis [7].

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But the K l ü v e r - B u c y s y n d r o m e has not been described in the acute f u l m i n a t ing cases o f H S E [2]. In a d d i t i o n , unilateral change o f the t e m p o r a l lobes has been e m p h a s i z e d f r o m the clinical a n d p a t h o l o g i c a l studies o f H S E [2, 3, 6, 12]. In the cases m e n t i o n e d a b o v e , however, the p a r t i a l o r c o m p l e t e K l ü v e r - B u c y s y n d r o m e a p p e a r e d following the acute phase, a n d bilateral changes o f the t e m p o r a l lobes including the limbic regions were f o u n d at the p o s t m o r t e m e x a m i n a t i o n . F u r t h e r m o r e , it is o f interest that there was an interval o f 2 to 4 weeks between the onset o f the illness a n d the occurrence o f the s y n d r o m e . The r e a s o n is uncertain. The s y n d r o m e m a y be c o n c e a l e d by d i s t u r b a n c e o f consciousness d u r i n g the acute phase. The inverval might suggest that it t o o k some time to s p r e a d to the o p p o s i t e side f r o m a unilateral lesion o f the t e m p o r a l lobes a n d limbic areas. W i t h the p r o g r e s s o f a n t i v i r a l agents, survival cases o f H S E are increasing a n d the K l ü v e r - B u c y s y n d r o m e s h o u l d be noticed in such cases, as a significant clinical s y n d r o m e suggesting b i l a t e r a l involvement o f the t e m p o r a l lobes a n d limbic regions.

References 1. Akai, J., Kato, Y., Takase, M.: Clinico-pathological study of Klüver-Bucy syndrome. Psychiatr. Neurol. Jpn. 79, 67--87 (1977) 2. Bennett, D. R., Zu Rhein, G. M., Roberts, T. S.: Acute necrotizing encephalitis. A diagnostic problem in temporal lobe disease: Report of three cases. Arch. Neurol. 6, 96--113 (1962) 3. Ch'ien, L. T., Boehm, R. M., Robinson, H., Liu, C., Frenkel, L. D.: Characteristic early electroencephalographic changes in herpes simplex encephalitis. Clinical and virologic studies. Arch. Neurol. 34, 361--364 (1977) 4. Hara, T., Okada, M.: A case of acute necrotizing encephalitis. Lesions in the limbic areas and Klüver-Bucy syndrome. Psychiatr. Neurol. Jpn. 65, 715--725 (1963) 5. Hiyamuta, E.: Klüver-Bucy syndrome. Geriatric Med. (Tokyo) 12, 713--717 (1974) 6. Illis, L. S., Gostling, J. V. T.: Herpes simplex encephalitis. Bristol: Scientechnica 1972 7. Johnson, R. T., Olson, L. C., Buescher, E. L.: Herpes simplex virus infections of the nervous system. Problems in laboratory diagnosis. Arch. Neurol. 18, 260--264 (1968) 8. Klüver, H., Bucy, P. C.: An analysis of certain effects of bilateral temporal lobectomy in the rhesus monkey, with special reference to "psychic blindness". J. Psychol. 5, 33--54 (1938) 9. Klüver, H., Bucy, P. C.: Preliminary analysis of functions of the temporal lobes in monkeys. Arch. Neurol. Psychiatr. 42, 979--1000 (1939) 10. Oxbury, J. M., MacCallum, F. O.: Herpes simplex virus encephalitis. Clinical features and residual damage. Postgr. Med. J. 49, 387--389 (1973) 11. Pilleri, G.: The Klüver-Bucy syndrome in man. A clinico-anatomical contribution to the function of the medial temporal lobe structures. Psychiat. Neurol. (Basel) 152, 65--103 (1966) 12. Radcliffe, W. B., Guinto, F. C., Jr., Adcodk, D. F., Krigman, M. R.: Herpes simplex encephalitis. A radiologic-pathologic study of 4 cases. Am. J. Roentgenol. 11, 263--272 (1971) 13. Shoji, H.: Clinical features of herpes simplex encephalitis. Clin. Neurol. (Tokyo) 8,491--498 (1973) 14. Terzian, H., Ore, G. D.: Syndrome of Klüver and Bucy. Reproduced in man by bilateral removal of the temporal lobes. Neurology (Minneap.) 5, 373--380 (1954) 15. Wallack, E., Hill, C.: Selective limbic deficits after encephalitis. South. Med. J. 69, 669--671 (1976) Received October 10, 1978