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Case of neurological and behavioral abnormalities: Due to Borna disease virus encephalitis?
Psychiatry
Research,
193
421193-196
Elsevier
Letter Case of Neurological and Behavioral Abnormalities: Due to Borna Disease Virus Encephalitis? To the Editors:
Borna disease (BD) is a well-known meningoencephalitis of horses and sheep in central Europe (Zwick et al., 1926). The strongly neurotropic viral agent has not yet been clearly characterized, but it seems to have properties of conventional and unconventional viruses (Duchala et al., 1989). In experimental BD of animals, great variability in symptomatology and course of illness has been seen, from peracute fatal course to latent course, depending on the host species and the virus variant used (Sprankel et al., 1978; Narayan et al., 1983; Ludwig et al., 1988). Pareses and behavioral abnormalities are typical. After intranasal infection of rats, the virus dissemination occurs intra-axonally along olfactory pathways to the brain (Carbone et al., 1987; Morales et al., 1988). The behavioral syndromes are related to inflammation and concomitant neurotransmitter alterations (Lipkin et al., 1988). The first human investigations were performed in psychiatric patients (Amsterdam et al., 1985; Rott et al., 1985) suggesting a possible etiological role of the BD virus (BDV) in affective psychoses. Although we found a higher prevalence of BDV serum antibodies in psychiatric than in surgical patients, our investigations showed a broad pattern of psychiatric diagnoses in BDVseropositive psychiatric patients, not significantly different from that in BDV-seronegative psychiatric patients (Bechter et al., 1987). The lack of diagnostic specificity, coupled with the failure of Bode et al. (1988) to find a higher prevalence of serum antibodies in psychiatric patients in another study, might argue against a pathogenic role of BDV in psychiatric patients. The first positive reports of elevated BDV-specific immuno-
0165-1781/92/$05.00
@ 1992 Elsevier Scientific
globulin G in cerebrospinal fluid, however, support a pathogenic role of BDV in psychiatric patients (Bechter et al., 1989). We hypothesized that a mixture of accidental and relevant findings of BDV-serum antibodies might exist and that in relevant psychiatric cases a possible BDV encephalitis might produce nonspecific psychiatric symptomatology or contribute, together with other pathogenic factors (e.g., genetic ones), to the development of a certain psychiatric disorder. If this were true, it would be hard to identify cases in which a BDV infection played a pathogenic role. In a further exploration of this question, we recently extended our studies to neurological patients. The following interesting case report might help to elucidate these questions. A 22-year-old man, working on his father’s farm, was admitted to a regional hospital by the emergency service, He had been in good health, but on this day was found unconscious by his parents somewhere in the farmhouse, after having been missing for more than an hour. He was somnolent upon arrival at the hospital. Physical examination revealed no further pathologic findings. A possible suicidal intoxication was ruled unlikely by examination of gastric contents and on the basis of the history reported by the relatives. Laboratory findings showed a slight elevation of creatinine phosphokinase (97 U/ 1 [ 10-801) and glutamic-pyruvic transaminase (34 U/l [O-22]) in serum, normal values for glutamic-oxalocetic transaminase, lactate dehydrogenase, urea-nitrogen, creatinine, sodium, potassium, calcium, glucose, prothrombin time, partial thromboplastin time, red blood cells, white blood cells,
Publishers
Ireland
Ltd.
194
hemoglobin, hematocrit, and mean corpuscular volume. Pulse frequency was 90/minute, blood pressure was 120/ 80 mmHg, and body temperature was 36.6 “C. Urinary examination was normal. The electrocardiogram showed some ventricular extrasystoles but was otherwise normal. Since the patient had cramps of the arms, epileptic seizures were considered and he was transferred to the neurological department. There he did not react when addressed. The pupils were dilated and not reactive to light; the ocular bulbi were rotated upwards. He continued to show myoclonic jerks of the arms, sometimes spreading to the legs. A preliminary diagnosis of epileptic seizures was made, and the patient received 10 mg diazepam and 750 mg phenytoin intravenously. The cramps ceased. The pupils and pupillary light reflexes became normal. The patient now reacted to simple commands (e.g., to press a hand). Motion of the arms and legs was reduced, monosynaptic reflexes were normal as before, and no pathologic reflexes were found. Findings of cranial computed tomography and X-ray of the thorax, skull and vertebrae were normal. Examination of the cerebrospinal fluid showed clear color, 5 cells/mm3 (lymphocytes), and normal values for protein content, albumin, immuno-gamma-globulin (IgG), and glucose. Doppler sonography of vertebral and supratrochlear arteries was normal. The electroencephalogram (EEG) showed a 9 cycles/ second (c/s) subdominant alpha rhythm, some theta waves of 6-8 c/s interjected with a lower voltage than the background activity. The patient remained somnolent on this day. The day after admission, somnolence disappeared; the patient received no medication at all. He now complained of headache, and a strange gait and behavioral disturbance were observed. He exhibited abnormal body postures, seemed to imitate another paretic patient, or actually had leg pareses with severity fluctuating throughout the day. He was anxious, depressive, and apathetic (311.00 DSM-III-R). On the third night after admission, he had a very severe headache with vomiting and for the first time a slightly elevated body temperature of 37.9 “C. One week after admission, he definitely showed paretic weakness in his right leg, with leg
dragging when walking, and reduced force predominantly in adduction and abduction of the hip and extension of the knee. He had no pathologic reflexes or sensibility disturbances. Magnetic resonance imaging of the brain and a second X-ray of the thorax and pelvis were normal. EEG on night 6 after admission showed a subdominant 8-9 c/s alpha rhythm. In the EEG and in the sleep EEG in stage A after Loomis repeated single and group steep waves of 5-7 c/s with amplitudes up to 200 PUV occurred, partially accentuated on the right side and partially generalized above all brain regions, suggestive of epileptic activity. The neurologists now assumed seizures, and the patient was treated with carbamazepine (600 mg a day). Investigation of the cerebrospinal fluid on day 13 showed 2 cells/ mm3 (lymphocytes) and normal values for albumin, IgG, protein content, and glucose. No elevated antibody titers were found against the adeno, picorna, herpes, polio, and Coxsackie viruses and the infectious agents of syphilis, borreliosis, ornithosis, influenza, parainfhtenza, early summer meningoencephalitis, and lymphocytic choriomeningitis in serum and cerebrospinal fluid. However, a possible BDV encephalitis was considered due to the presence of BDV serum antibodies of 1:lO (IgG antibodies) similar to that found in horses with acute BD (Lange et al., 1987). We therefore investigated the horses and sheep at the patient’s farm for antibodies against BDV: 1 of 4 horses and 4 of 10 sheep showed BDV serum antibodies. The BDV-seropositive horse was known to be anxious and excitable and was avoided by the members of the riders club because of unexpected phobic reactions. No information was available about the behavior of the sheep. Catamnesis of the Patient. After 3 weeks of hospital treatment, the patient continued to suffer from a slight paresis of his right leg for a period of 1% years. Electromyography of the slightly paretic muscle groups (musculus quadriceps femoris and femoral abductors) showed normal muscle activity patterns at rest and during activation 10 weeks after the beginning of the symptomatology; there were no signs of denervation. From the onset of the disorder, the patient additionally complained of chronic severe headache and muscle cramps in his legs,
195 gradually ameliorating over the time span of 1 year. The EEG showed a slow 8-9 c/s alpha rhythm at the beginning and slowed down to 7.5-8 c/s with frequent single and grouped theta waves of 5-7 c/s within a period of 2 months after onset of the disease. It normalized to a slow 8-9 c/s alpha rhythm about 6 months after onset and has remained normal to the time of report (2 years). Seizures or possible seizures did not occur again, even when carbamazepine medication was discontinued 1% years after the acute phase. All disturbances have now, 2 years later, nearly completely ameliorated. Subjectively, the patient now feels symptom-free. The patient’s relatives, however, report that he has changed in two aspects since this disorder: a very slight paresis of his right leg (slight leg dragging) and a personality change, in that he becomes easily excited and angry and tends to be somewhat depressive. However, he does not meet criteria for affective disorders. There is no family history of known psychiatric disorders. BD is a typically persistent slow infection in several animal species. It was thought to be nonpathogenic for humans, but this has been questioned by the findings of BDV serum antibodies in psychiatric patients and normals. It is well known that slow virus infections do not cause cerebrospinal fluid abnormalities despite clinical encephalitis. If histological verification of the encephalitis is not possible because the disorder itself does not lead to death and ethical reasons do not allow biopsy, a causal relationship between serum antibodies against a certain virus and a clinical syndrome possibly due to encephalitis caused by that virus is difficult to establish in humans. Clinical and epidemiological observations are therefore important. In the patient reported here, there is a great deal of similarity in symptomatology and course of the disorder to that of BDV-infected animals: paresis of fluctuating intensity, weakness of the legs, and behavioral abnormalities in the form of excitability and “depression” have been described. Apparative and laboratory findings in our patient did not prove BDV encephalitis. We were, however, able to demonstrate BDV serum antibodies in several animals at the patient’s farm. The
only BDV-seropositive horse showed behavioral alterations comparable to those described in BD (Lange et al., 1987). Although we cannot definitely demonstrate an infectious chain, a BDV infection from the animals seems possible. At the beginning of the disorder, a cerebral seizure probably occurred in the patient. This fits well with acute encephalitis. In the case of epilepsy, further seizures should have occurred. Furthermore, the patient developed a clinical syndrome of neurological and psychiatric symptomatology resembling that of BD in animals and not typical of another known encephalitis. The BDV serum antibody titer in our patient remained unchanged over the 2-year observation period as in most BDVseropositive cases we have seen (unpublished results). BDV serum antibody titers may be low or high (1:5-1:320) in acute BD of horses (Lange et al., 1987) the titer not indicating the activity of the encephalitis. BDV serum antibodies apparently play no role in the pathogenesis of BD, but the disease is caused by a virus-induced immunopathological reaction in which a T-cell line (CD 4+) plays an important role (Deschl et al., 1990). We therefore think that our patient may have suffered from acute BDV-encephalitis with neurological and psychiatric symptomatology. On the basis of the results of animal experiments (Sprankel et al., 1978; Narayan et al., 1983), we believe that psychiatric symptomatology alone could also occur in possible BD in humans, which may be nonspecific without organic brain syndrome, due only to slight encephalitis in the limbic system, which is preferentially lesioned by BD. In this way BDV might serve as a causative factor or cofactor for the development of “endogenous” or schizophrenic psychoses, as hypothesized earlier (Crow, 1986). Genetic factors should play an important role in the development of the clinical symptomatology according to the results of animal experiments (Herzog et al., 1991). Acknowledgments. We thank the Department of Internal Medicine and the Neurological Department of the Kliniken Gunzburg and the Staatl. Veterinlramt Giinzburg for kind collaboration.
196 References Amsterdam, J.D.; Winokur, A.; Dyson, W.; Herzog, S.; Gonzales, F.; Rott, R.; and Koprowski, H. Borna disease virus: A possible etiologic factor in human affective disorders? Archives of General Psychiatry, 42:1093-1096, 1985. Bechter, K.; Herzog, S.; Fleischer, B.; Schtittler, R.; and Rott, R. Magnetic resonance imaging in psychiatric patients with and without serum antibodies against Borna disease. Nervenarzt, 58:617-624, 1987. Bechter, K.; Herzog, S.; Schiittler, R.; and Rott, R. Die Boma’sche Krankheit-wahrscheinlich such eine menschliche Krankheit: neue Ergebnisse. In: Saletu, B., ed. Biologische Psychiatrie. Stuttgart: Thieme, 1989. pp. 17-21. Bode, L.; Riegel, S.; Ludwig, H.; Amsterdam, J.D.; Lange, W.; and Koprowski, H. Borna disease virus-specific antibodies in patients with HIV infection and with mental disorders. Lancet, 17:689, 1988. Carbone, K.M.; Duchala, C.S.; Griffin, J.W.; Kincaid, A.L.; and Narayan, 0. Pathogenesis of Borna disease in rats: Evidence that intra-axonal spread is the major route for virus dissemination and the determinant for disease incubation. Journal of Virology, 11:3431-3440, 1987. Crow, T.J. A re-evaluation of the viral hypothesis: Is psychosis the result of retroviral integration at a site close to the cerebral dominance gene? In: Kerr, A., and Snaith, P., eds. Contemporary Issues in Schizophrenia. London: Royal College of Psychiatrists, Gaskell, 1986. pp. 241-257. Deschl, U.; Stitz, L.; Herzog, S.; Frese, K.; and Rott, R. Determination of immune cells and expression of major histocompatability of complex class II antigen in encephalitic lesions of experimental Borna disease. Acta Neuropathologica, 81:41-50, 1990. Duchala, C.S.; Carbone, K.M.; and Narayan, 0. Preliminary studies on the biology of Borna disease virus. Journal of General Virology, 70:3507-3511, 1989. Herzog, S.; Frese, K.; and Rott, R. Studies on the genetic control of resistance of black hooded rats to Borna disease. Journal of General Virology, 721535-540, 199 1. Lange, H.; Herzog, S.; Herbst, W.; and Schliesser, T. Seroepidemiologische Untersuchungen zur Boma’schen Krankheit (Ansteckende Gehirn- und Rtickenmarlcsentztindung) der Pferde. Tieriirztliche Umschau, 42:938-946, 1987.
Lipkin, W.; Carbone, K.M.; Wilson, M.D.; Duchala, C.S.; Narayan, 0.; and Oldstone, M.B.A. Neurotransmitter abnormalities in Borna disease. Brain Research, 475:366-370, 1988. Ludwig, H.; Bode, L.; and Gosztonyi, G. Borna disease-A persistent virus infection of the central nervous system. Progress in Medical Virology, 35:107-151, 1988. Morales, J.A.; Herzog, S.; Kompter, C.; Frese, K.; and Rott, R. Axonal transport of Borna disease virus along olfactory pathways in spontaneously and experimentally infected rats. Medical Microbiology and Immunology, 177:51-68, 1988. Narayan, 0.; Herzog, S.; Frese, K.; Scheefers, H.; and Rott, R. Pathogenesis of Borna disease in rats: Immune-mediated viral opthalmoencephalopathy causing blindness and behavioral abnormalities. Journal of Infectious Diseases, 148:305-315, 1983. Rott, R.; Herzog, S.; Fleischer, B.; Winokur, A.; Amsterdam, J.; Dyson, W.; and Koprowski, H. Detection of serum-antibodies to Borna disease virus in patients with psychiatric disorders. Science, 228:755-756, 1985. Sprankel, H.; Richarz, K.; Ludwig, H.; and Rott, R. Behavior alterations in tree shrews (tupaia glis, Diard 1820) induced by Borna disease virus. Medical Microbiology and Immunology, 165:1-18, 1978. Zwick, W.; Seifried, 0.; and Witte, J. Experimentelle Untersuchungen uber die seuchenhafte Gehirnund Riickenmarksentzlndung der Pferde (Borna’sche Krankeit). Infektionskrankheiten der Haustiere, 30:42- 136, 1926. Karl Bechter, M.D. Reinhold Schiittler, M.D. University of Ulm Department of Psychiatry II and Department of Psychiatry of the Bezirkskrankenhaus Giinzburg, Germany Sibylle Herzog. Ph.D. Institute of Virology Justus-Liebig-University Giepen, Germany Received February 22.1991; revised September 23, 1991.
Research,
193
421193-196
Elsevier
Letter Case of Neurological and Behavioral Abnormalities: Due to Borna Disease Virus Encephalitis? To the Editors:
Borna disease (BD) is a well-known meningoencephalitis of horses and sheep in central Europe (Zwick et al., 1926). The strongly neurotropic viral agent has not yet been clearly characterized, but it seems to have properties of conventional and unconventional viruses (Duchala et al., 1989). In experimental BD of animals, great variability in symptomatology and course of illness has been seen, from peracute fatal course to latent course, depending on the host species and the virus variant used (Sprankel et al., 1978; Narayan et al., 1983; Ludwig et al., 1988). Pareses and behavioral abnormalities are typical. After intranasal infection of rats, the virus dissemination occurs intra-axonally along olfactory pathways to the brain (Carbone et al., 1987; Morales et al., 1988). The behavioral syndromes are related to inflammation and concomitant neurotransmitter alterations (Lipkin et al., 1988). The first human investigations were performed in psychiatric patients (Amsterdam et al., 1985; Rott et al., 1985) suggesting a possible etiological role of the BD virus (BDV) in affective psychoses. Although we found a higher prevalence of BDV serum antibodies in psychiatric than in surgical patients, our investigations showed a broad pattern of psychiatric diagnoses in BDVseropositive psychiatric patients, not significantly different from that in BDV-seronegative psychiatric patients (Bechter et al., 1987). The lack of diagnostic specificity, coupled with the failure of Bode et al. (1988) to find a higher prevalence of serum antibodies in psychiatric patients in another study, might argue against a pathogenic role of BDV in psychiatric patients. The first positive reports of elevated BDV-specific immuno-
0165-1781/92/$05.00
@ 1992 Elsevier Scientific
globulin G in cerebrospinal fluid, however, support a pathogenic role of BDV in psychiatric patients (Bechter et al., 1989). We hypothesized that a mixture of accidental and relevant findings of BDV-serum antibodies might exist and that in relevant psychiatric cases a possible BDV encephalitis might produce nonspecific psychiatric symptomatology or contribute, together with other pathogenic factors (e.g., genetic ones), to the development of a certain psychiatric disorder. If this were true, it would be hard to identify cases in which a BDV infection played a pathogenic role. In a further exploration of this question, we recently extended our studies to neurological patients. The following interesting case report might help to elucidate these questions. A 22-year-old man, working on his father’s farm, was admitted to a regional hospital by the emergency service, He had been in good health, but on this day was found unconscious by his parents somewhere in the farmhouse, after having been missing for more than an hour. He was somnolent upon arrival at the hospital. Physical examination revealed no further pathologic findings. A possible suicidal intoxication was ruled unlikely by examination of gastric contents and on the basis of the history reported by the relatives. Laboratory findings showed a slight elevation of creatinine phosphokinase (97 U/ 1 [ 10-801) and glutamic-pyruvic transaminase (34 U/l [O-22]) in serum, normal values for glutamic-oxalocetic transaminase, lactate dehydrogenase, urea-nitrogen, creatinine, sodium, potassium, calcium, glucose, prothrombin time, partial thromboplastin time, red blood cells, white blood cells,
Publishers
Ireland
Ltd.
194
hemoglobin, hematocrit, and mean corpuscular volume. Pulse frequency was 90/minute, blood pressure was 120/ 80 mmHg, and body temperature was 36.6 “C. Urinary examination was normal. The electrocardiogram showed some ventricular extrasystoles but was otherwise normal. Since the patient had cramps of the arms, epileptic seizures were considered and he was transferred to the neurological department. There he did not react when addressed. The pupils were dilated and not reactive to light; the ocular bulbi were rotated upwards. He continued to show myoclonic jerks of the arms, sometimes spreading to the legs. A preliminary diagnosis of epileptic seizures was made, and the patient received 10 mg diazepam and 750 mg phenytoin intravenously. The cramps ceased. The pupils and pupillary light reflexes became normal. The patient now reacted to simple commands (e.g., to press a hand). Motion of the arms and legs was reduced, monosynaptic reflexes were normal as before, and no pathologic reflexes were found. Findings of cranial computed tomography and X-ray of the thorax, skull and vertebrae were normal. Examination of the cerebrospinal fluid showed clear color, 5 cells/mm3 (lymphocytes), and normal values for protein content, albumin, immuno-gamma-globulin (IgG), and glucose. Doppler sonography of vertebral and supratrochlear arteries was normal. The electroencephalogram (EEG) showed a 9 cycles/ second (c/s) subdominant alpha rhythm, some theta waves of 6-8 c/s interjected with a lower voltage than the background activity. The patient remained somnolent on this day. The day after admission, somnolence disappeared; the patient received no medication at all. He now complained of headache, and a strange gait and behavioral disturbance were observed. He exhibited abnormal body postures, seemed to imitate another paretic patient, or actually had leg pareses with severity fluctuating throughout the day. He was anxious, depressive, and apathetic (311.00 DSM-III-R). On the third night after admission, he had a very severe headache with vomiting and for the first time a slightly elevated body temperature of 37.9 “C. One week after admission, he definitely showed paretic weakness in his right leg, with leg
dragging when walking, and reduced force predominantly in adduction and abduction of the hip and extension of the knee. He had no pathologic reflexes or sensibility disturbances. Magnetic resonance imaging of the brain and a second X-ray of the thorax and pelvis were normal. EEG on night 6 after admission showed a subdominant 8-9 c/s alpha rhythm. In the EEG and in the sleep EEG in stage A after Loomis repeated single and group steep waves of 5-7 c/s with amplitudes up to 200 PUV occurred, partially accentuated on the right side and partially generalized above all brain regions, suggestive of epileptic activity. The neurologists now assumed seizures, and the patient was treated with carbamazepine (600 mg a day). Investigation of the cerebrospinal fluid on day 13 showed 2 cells/ mm3 (lymphocytes) and normal values for albumin, IgG, protein content, and glucose. No elevated antibody titers were found against the adeno, picorna, herpes, polio, and Coxsackie viruses and the infectious agents of syphilis, borreliosis, ornithosis, influenza, parainfhtenza, early summer meningoencephalitis, and lymphocytic choriomeningitis in serum and cerebrospinal fluid. However, a possible BDV encephalitis was considered due to the presence of BDV serum antibodies of 1:lO (IgG antibodies) similar to that found in horses with acute BD (Lange et al., 1987). We therefore investigated the horses and sheep at the patient’s farm for antibodies against BDV: 1 of 4 horses and 4 of 10 sheep showed BDV serum antibodies. The BDV-seropositive horse was known to be anxious and excitable and was avoided by the members of the riders club because of unexpected phobic reactions. No information was available about the behavior of the sheep. Catamnesis of the Patient. After 3 weeks of hospital treatment, the patient continued to suffer from a slight paresis of his right leg for a period of 1% years. Electromyography of the slightly paretic muscle groups (musculus quadriceps femoris and femoral abductors) showed normal muscle activity patterns at rest and during activation 10 weeks after the beginning of the symptomatology; there were no signs of denervation. From the onset of the disorder, the patient additionally complained of chronic severe headache and muscle cramps in his legs,
195 gradually ameliorating over the time span of 1 year. The EEG showed a slow 8-9 c/s alpha rhythm at the beginning and slowed down to 7.5-8 c/s with frequent single and grouped theta waves of 5-7 c/s within a period of 2 months after onset of the disease. It normalized to a slow 8-9 c/s alpha rhythm about 6 months after onset and has remained normal to the time of report (2 years). Seizures or possible seizures did not occur again, even when carbamazepine medication was discontinued 1% years after the acute phase. All disturbances have now, 2 years later, nearly completely ameliorated. Subjectively, the patient now feels symptom-free. The patient’s relatives, however, report that he has changed in two aspects since this disorder: a very slight paresis of his right leg (slight leg dragging) and a personality change, in that he becomes easily excited and angry and tends to be somewhat depressive. However, he does not meet criteria for affective disorders. There is no family history of known psychiatric disorders. BD is a typically persistent slow infection in several animal species. It was thought to be nonpathogenic for humans, but this has been questioned by the findings of BDV serum antibodies in psychiatric patients and normals. It is well known that slow virus infections do not cause cerebrospinal fluid abnormalities despite clinical encephalitis. If histological verification of the encephalitis is not possible because the disorder itself does not lead to death and ethical reasons do not allow biopsy, a causal relationship between serum antibodies against a certain virus and a clinical syndrome possibly due to encephalitis caused by that virus is difficult to establish in humans. Clinical and epidemiological observations are therefore important. In the patient reported here, there is a great deal of similarity in symptomatology and course of the disorder to that of BDV-infected animals: paresis of fluctuating intensity, weakness of the legs, and behavioral abnormalities in the form of excitability and “depression” have been described. Apparative and laboratory findings in our patient did not prove BDV encephalitis. We were, however, able to demonstrate BDV serum antibodies in several animals at the patient’s farm. The
only BDV-seropositive horse showed behavioral alterations comparable to those described in BD (Lange et al., 1987). Although we cannot definitely demonstrate an infectious chain, a BDV infection from the animals seems possible. At the beginning of the disorder, a cerebral seizure probably occurred in the patient. This fits well with acute encephalitis. In the case of epilepsy, further seizures should have occurred. Furthermore, the patient developed a clinical syndrome of neurological and psychiatric symptomatology resembling that of BD in animals and not typical of another known encephalitis. The BDV serum antibody titer in our patient remained unchanged over the 2-year observation period as in most BDVseropositive cases we have seen (unpublished results). BDV serum antibody titers may be low or high (1:5-1:320) in acute BD of horses (Lange et al., 1987) the titer not indicating the activity of the encephalitis. BDV serum antibodies apparently play no role in the pathogenesis of BD, but the disease is caused by a virus-induced immunopathological reaction in which a T-cell line (CD 4+) plays an important role (Deschl et al., 1990). We therefore think that our patient may have suffered from acute BDV-encephalitis with neurological and psychiatric symptomatology. On the basis of the results of animal experiments (Sprankel et al., 1978; Narayan et al., 1983), we believe that psychiatric symptomatology alone could also occur in possible BD in humans, which may be nonspecific without organic brain syndrome, due only to slight encephalitis in the limbic system, which is preferentially lesioned by BD. In this way BDV might serve as a causative factor or cofactor for the development of “endogenous” or schizophrenic psychoses, as hypothesized earlier (Crow, 1986). Genetic factors should play an important role in the development of the clinical symptomatology according to the results of animal experiments (Herzog et al., 1991). Acknowledgments. We thank the Department of Internal Medicine and the Neurological Department of the Kliniken Gunzburg and the Staatl. Veterinlramt Giinzburg for kind collaboration.
196 References Amsterdam, J.D.; Winokur, A.; Dyson, W.; Herzog, S.; Gonzales, F.; Rott, R.; and Koprowski, H. Borna disease virus: A possible etiologic factor in human affective disorders? Archives of General Psychiatry, 42:1093-1096, 1985. Bechter, K.; Herzog, S.; Fleischer, B.; Schtittler, R.; and Rott, R. Magnetic resonance imaging in psychiatric patients with and without serum antibodies against Borna disease. Nervenarzt, 58:617-624, 1987. Bechter, K.; Herzog, S.; Schiittler, R.; and Rott, R. Die Boma’sche Krankheit-wahrscheinlich such eine menschliche Krankheit: neue Ergebnisse. In: Saletu, B., ed. Biologische Psychiatrie. Stuttgart: Thieme, 1989. pp. 17-21. Bode, L.; Riegel, S.; Ludwig, H.; Amsterdam, J.D.; Lange, W.; and Koprowski, H. Borna disease virus-specific antibodies in patients with HIV infection and with mental disorders. Lancet, 17:689, 1988. Carbone, K.M.; Duchala, C.S.; Griffin, J.W.; Kincaid, A.L.; and Narayan, 0. Pathogenesis of Borna disease in rats: Evidence that intra-axonal spread is the major route for virus dissemination and the determinant for disease incubation. Journal of Virology, 11:3431-3440, 1987. Crow, T.J. A re-evaluation of the viral hypothesis: Is psychosis the result of retroviral integration at a site close to the cerebral dominance gene? In: Kerr, A., and Snaith, P., eds. Contemporary Issues in Schizophrenia. London: Royal College of Psychiatrists, Gaskell, 1986. pp. 241-257. Deschl, U.; Stitz, L.; Herzog, S.; Frese, K.; and Rott, R. Determination of immune cells and expression of major histocompatability of complex class II antigen in encephalitic lesions of experimental Borna disease. Acta Neuropathologica, 81:41-50, 1990. Duchala, C.S.; Carbone, K.M.; and Narayan, 0. Preliminary studies on the biology of Borna disease virus. Journal of General Virology, 70:3507-3511, 1989. Herzog, S.; Frese, K.; and Rott, R. Studies on the genetic control of resistance of black hooded rats to Borna disease. Journal of General Virology, 721535-540, 199 1. Lange, H.; Herzog, S.; Herbst, W.; and Schliesser, T. Seroepidemiologische Untersuchungen zur Boma’schen Krankheit (Ansteckende Gehirn- und Rtickenmarlcsentztindung) der Pferde. Tieriirztliche Umschau, 42:938-946, 1987.
Lipkin, W.; Carbone, K.M.; Wilson, M.D.; Duchala, C.S.; Narayan, 0.; and Oldstone, M.B.A. Neurotransmitter abnormalities in Borna disease. Brain Research, 475:366-370, 1988. Ludwig, H.; Bode, L.; and Gosztonyi, G. Borna disease-A persistent virus infection of the central nervous system. Progress in Medical Virology, 35:107-151, 1988. Morales, J.A.; Herzog, S.; Kompter, C.; Frese, K.; and Rott, R. Axonal transport of Borna disease virus along olfactory pathways in spontaneously and experimentally infected rats. Medical Microbiology and Immunology, 177:51-68, 1988. Narayan, 0.; Herzog, S.; Frese, K.; Scheefers, H.; and Rott, R. Pathogenesis of Borna disease in rats: Immune-mediated viral opthalmoencephalopathy causing blindness and behavioral abnormalities. Journal of Infectious Diseases, 148:305-315, 1983. Rott, R.; Herzog, S.; Fleischer, B.; Winokur, A.; Amsterdam, J.; Dyson, W.; and Koprowski, H. Detection of serum-antibodies to Borna disease virus in patients with psychiatric disorders. Science, 228:755-756, 1985. Sprankel, H.; Richarz, K.; Ludwig, H.; and Rott, R. Behavior alterations in tree shrews (tupaia glis, Diard 1820) induced by Borna disease virus. Medical Microbiology and Immunology, 165:1-18, 1978. Zwick, W.; Seifried, 0.; and Witte, J. Experimentelle Untersuchungen uber die seuchenhafte Gehirnund Riickenmarksentzlndung der Pferde (Borna’sche Krankeit). Infektionskrankheiten der Haustiere, 30:42- 136, 1926. Karl Bechter, M.D. Reinhold Schiittler, M.D. University of Ulm Department of Psychiatry II and Department of Psychiatry of the Bezirkskrankenhaus Giinzburg, Germany Sibylle Herzog. Ph.D. Institute of Virology Justus-Liebig-University Giepen, Germany Received February 22.1991; revised September 23, 1991.