5-04-06 Profile of cellular immune reponse among HAM/TSP patients in Rio de Janeiro

1
Bacterial, Fungal & Wral Infections of the Nervous System S277 have been a number of reports suggesting that infection may be associated with the development of a myelopathy which shares some similarities that are associated with HTLV-I infection (HAMITSP). To further investigate this, we have evaluated HTLV-II infection and clinical outcomes in the state of Rio Grande do Sul, in southern Brazil. Serological studies initiated in 1994 in Port0 Alegre, the capital of Rio Grande do Sul, have shown a medium prevalence of HTLV-l/II infections of 0.4, of which 12.5% were confirmed as being HTLV-II. Clinical evaluatims have revealed neurological disorders in six HTLV-II infected individuals. These included three Caucasian female blood donors, two of whom were of Amerindian descent, and three other individuals who were members of a single family. The latter included the father who had a history of intravenous drug abuse, his wife and son. None of the HTLV-II infected individuals were co-infected with HIV. The clinical features observed can be summarised as follows: micturictional symtoms were present in five of six, and urodynamic evaluation was abnormal in four (hyperreflexia, uninhibited contractions, intermittent voiding). Sensory complaints, pyramidal signs and hypopallesthesia were observed in five of six patients. Slight ataxia was evident in all six. SEPs of the lower limbs showed conduction delays in three of five. CSF examination revealed HTLV-II antibodies, and an inflammatory pattern in three patients. No lesions were evident on MRI and CT scan exams. Immunologic studies on the three blood donors demonstrated spontaneous proliferation of PBLs, but to a lesser degree than that reported in patients with HAM/TSP. Molecular analysis demonstrated that both all three family members were infected with HTLV-llc and one of the blood donors, while the other two donors with HTLV-lib subtypes, respectively. The latter is the first demonstration of HTLV-lib infection in Brazil. The present study strongly supports the view that HTLV-II infection is associated with a spectrum of neurological disorders where myelopathy and ataxia are prominent. Moreover our preliminary molecular studies suggest that there would appear to be no specific correlation between infection with a particular HTLV-II subtype and the development of neurological disease. 5-04-04 Human herpes virus 8 (HHV-8) in acute inflammatory diseases of the central nervous system (CNS) E. Merelli, Ft. Bedin, P. Sola. Department of Neurologyr University of Modena, b/y DNA sequences of a new herpes virus named Kaposi Sarcoma Herpes Virus (KSHV) or HHV-8 has been identified in Kaposi sarcoma (KS) tissues from patients with AIDS. HHV-8 can be found in the tissues of immunocompromized subjects and CD4 T+ cells and CD19+ B cells are thought to be the natu- ral target of the virus. Since lymphocytes activation is considered crucial in the cccurrence of acute inflammatory diseases of the CNS, we investigated whether HHV-8 may be associated with neurological infection. To this purpose we deemed appropriate the use of the PCR to identify HHV-8 sequences in the serum and cerebral spinal fluid (CSF) from patients with encephalitis, meningi- tis, myelitis as well as from normal sera and CSF specimen for control. HHV-8 specific sequences have been investigated in serum and CSF of 23 patients (15 females, 8 males, mean age 37 years) affected by acute inflammatory disease of the CNS and samples from 15 normal adults. PCR for HHV-8 se- quences was perfoned using specific primers amplifying a fragment of 233 base pairs (bp) as described (Chang Y et al. 1994 Science 266: 1885). The PCR products were hybridized with an internal oligonucleotide probe specific for HHV-8, and labelled with y=P-ATP. In two cases of encephalitis and in one of myelomeningoencephalitis HHV-8 specific sequences have been found in serum and CSF, while the 15 normal sera and CSF were negative for the virus. Although these data are unsufficient to support an aethiological role for HHV-8 in the CNS infection, nevertheless a reactivation of HHV-8 a setting of immune impainent cannot be rouled out. 5-04-05 Neurolues today A. Milicevic-Kalasic ‘, V. Mat-tic 2, J. llic ‘, T. Lepic2. ’ institute of GerontobgK Home Treatment and Care, Military Medical Academy Belgrade, Yugoslavia, ‘Clinic of neurology; Military Medical Academy, Belgrade, Yugoslavia In spite of assumption that lues is eradicated all over the world our reported denies it. This paper has attention to present two cases with neurolues: one with acquired and the other one with congenital neurolues. The first case report reefers on 44 year old man with these main complaints: painful lumbar syndrome, myopathy and encephalopathia. Per anamnesis it is found out that lues was diagnosed in his seventies with positive VDRL reaction. The second one is dealing with 82 years old women with visual illusions, impairment of joint position function, convulsions, present Argyl-Robertson sign, Charwt joint and gummas in her clinical feature. As previous patient she was diagnosed by VDRL and Nelson test also. There is date that her father was treated as luetic patient. l-x-l 5 04 06 Profile of cellular immune reponse among HAWISP patients in Rio de Janeiro R.B. Corrha, M. Puccioni-Sohler, S.A.P. Novis, M.S.P. Oliveira, M.S.M. Carvalho. HUCFFAJFRJ; INCA/MS; HEMOPEBJ, Rio de Janeiro, Brasil ObJective: To analyze the profiles of cellular immune reponse in HAM/TSP patients correlating with the time of disease. DeeignlMethods: Twenty HAMfTSP patients attending in a neurological center in Rio de Janeiro (HUCFWUFRJ) were analysed. The diagnosis was made based on WHO criteria. Patients were divided in two groups according to the time of disease: 8 patients with less than five years of disease and 12 with more than five years. Heparinized blood samples were collected and peripheral blood mononuclear cells were isolated by Ficoll - Hypaque gradi- ent centrifugation. Cells were labeled with the immunofluorescent monoclonal probes (CD4, CD8, CD3, CD19, CD45, CD25, HLADR). Lymphocytes subsets percentages were determined by cytofluorometric analysis. Results: The average age was 49.5 years (24-66) in the first group and 58.3 years (44-75) in the second; average time of disease was 3 and 10.8 years respectively. There was one male in the first group and two in the second. The mean percentages of lymphocytes subsets in the two groups were respectively: CD4 - 370/o/43.58%, CD8 - 270/o/26.6%, CD3 - 83.9%/66.5%, CD19-12.6%/8.7%. CD45-67.5%/92.8%, CD25-34.6%/21.9%and HLADR - 33.6%/37.4%. Discus&on: The results shows changes in the distribution of lymphocytes subsets in HAMfTSP patients suggesting immune activation. Elevated percent- age of CD25 in the group with less than 5 years of disease maybs an indicator of disease activity. No major other differences were observed in both groups as a result of the time of disease. 15-04-07 1 Activities of cathepsins B and L in peripheral blood of patients with human T-lymphotrophic virus type 1 (HTLV-l)-associated myelopathy R. Sugihara, T. Kumamoto, H. Ueyama, M. Kondo, S. Nagao, T. Shigenaga, T. Tsuda. Third Department of Internal Medicine, Oira Medical University, Oita, Japan Human T-lymphotrophic virus type 1 (HTLV-1) is the etiologic agent in a slowly progressive spastic paraparesis, known as HTLV-l-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). Despite association with several abnomal immune phenomena, the mechanism of neural tissue damage by its infection remains virtually obscure. We evaluated the levels of two lysosomal proteases, cathepsins Band L, in peripheral blood mononuclear cells (PBMCs) and serum from HAM patients. PBMCs and sera were obtained from 7 patients with HAM (4 women and 3 men; age range, 36-76 years), 8 patients with other neurological diseases (ONDs), and 10 normal healthy controls. The diagnosis of HAM was based on the criteria of Osame and colleagues (1986). Anti-HTLV-1 antibody titers were elevated in the serum (256102,400 X) and cerebral spinal fluid (16-512 X) in all HAM patients. The activities of both proteases were assayed by the method of Barrett (1980). The activities of cathepsins B and L in PBMCs of HAM patients were significantly higher compared with normal control (cathepsin B, p = 0.01; cathepsin L, p < O.OOi), while there was significant difference only in cathepsin L activities between HAM patients and OND patients (p = 0.005). There were no significant difference in the activities of both cathepsins in serum from each group. This result suggests that cathepsins B and L in PBMCs may play a certain role in the inflammatory process or pathogenesis of HAMTTSP. I 5 04 08 Cavernous sinus syndrome: A clinical comparison between mucormycosis and non-mucormycosis Somsak Tiamkao’, Suthipun Jitpimolmard ‘, Verajit Chotmongkol ’ , Benjapom Nitinavakam *. ‘Division of Neurobg)! Department of Medicine, Khon Kaen Univefsi~ Khon Kaen, Thailand, *Department of Radiology. Faculty of Medicine, Khon Kaen Universitv, Khon Kaen, Thailand Introduction: Cavernous sinus syndrome is a disorder characterized by paral- ysis of cranial nerve 3, 4, 6 and 5. Causes of this syndrome are infectious and non-infectious source, such as mucormycosis, bacteria and malignancy. Delay in diagnosis and improper management contributed to high mortality rate. We report cavernous sinus syndrome patients at Srinagarind Hospital for recogni- tion and clinical comparison between mucormycosis and non-mucormycosis. Patient and Method: Review of patient charts from 1985 to 1994 at Sri- nagarind Hospital, Department of Medicine, Faculty of Medicine, Khon Kaen University, with sinus thrombosis. Result: There were 25 patients, 9 male, 16 female, male to female ratio was 1:1.7, age range from 30-79 years, mean was 55.08 years. Common pre-

Transcript of 5-04-06 Profile of cellular immune reponse among HAM/TSP patients in Rio de Janeiro

Bacterial, Fungal & Wral Infections of the Nervous System S277

have been a number of reports suggesting that infection may be associated with the development of a myelopathy which shares some similarities that are associated with HTLV-I infection (HAMITSP). To further investigate this, we have evaluated HTLV-II infection and clinical outcomes in the state of Rio Grande do Sul, in southern Brazil. Serological studies initiated in 1994 in Port0 Alegre, the capital of Rio Grande do Sul, have shown a medium prevalence of HTLV-l/II infections of 0.4, of which 12.5% were confirmed as being HTLV-II. Clinical evaluatims have revealed neurological disorders in six HTLV-II infected individuals. These included three Caucasian female blood donors, two of whom were of Amerindian descent, and three other individuals who were members of a single family. The latter included the father who had a history of intravenous drug abuse, his wife and son. None of the HTLV-II infected individuals were co-infected with HIV. The clinical features observed can be summarised as follows: micturictional symtoms were present in five of six, and urodynamic evaluation was abnormal in four (hyperreflexia, uninhibited contractions, intermittent voiding). Sensory complaints, pyramidal signs and hypopallesthesia were observed in five of six patients. Slight ataxia was evident in all six. SEPs of the lower limbs showed conduction delays in three of five. CSF examination revealed HTLV-II antibodies, and an inflammatory pattern in three patients. No lesions were evident on MRI and CT scan exams. Immunologic studies on the three blood donors demonstrated spontaneous proliferation of PBLs, but to a lesser degree than that reported in patients with HAM/TSP. Molecular analysis demonstrated that both all three family members were infected with HTLV-llc and one of the blood donors, while the other two donors with HTLV-lib subtypes, respectively. The latter is the first demonstration of HTLV-lib infection in Brazil. The present study strongly supports the view that HTLV-II infection is associated with a spectrum of neurological disorders where myelopathy and ataxia are prominent. Moreover our preliminary molecular studies suggest that there would appear to be no specific correlation between infection with a particular HTLV-II subtype and the development of neurological disease.

5-04-04 Human herpes virus 8 (HHV-8) in acute inflammatory diseases of the central nervous system (CNS)

E. Merelli, Ft. Bedin, P. Sola. Department of Neurologyr University of Modena, b/y

DNA sequences of a new herpes virus named Kaposi Sarcoma Herpes Virus (KSHV) or HHV-8 has been identified in Kaposi sarcoma (KS) tissues from patients with AIDS. HHV-8 can be found in the tissues of immunocompromized subjects and CD4 T+ cells and CD19+ B cells are thought to be the natu- ral target of the virus. Since lymphocytes activation is considered crucial in the cccurrence of acute inflammatory diseases of the CNS, we investigated whether HHV-8 may be associated with neurological infection. To this purpose we deemed appropriate the use of the PCR to identify HHV-8 sequences in the serum and cerebral spinal fluid (CSF) from patients with encephalitis, meningi- tis, myelitis as well as from normal sera and CSF specimen for control. HHV-8 specific sequences have been investigated in serum and CSF of 23 patients (15 females, 8 males, mean age 37 years) affected by acute inflammatory disease of the CNS and samples from 15 normal adults. PCR for HHV-8 se- quences was perfoned using specific primers amplifying a fragment of 233 base pairs (bp) as described (Chang Y et al. 1994 Science 266: 1885). The PCR products were hybridized with an internal oligonucleotide probe specific for HHV-8, and labelled with y=P-ATP. In two cases of encephalitis and in one of myelomeningoencephalitis HHV-8 specific sequences have been found in serum and CSF, while the 15 normal sera and CSF were negative for the virus. Although these data are unsufficient to support an aethiological role for HHV-8 in the CNS infection, nevertheless a reactivation of HHV-8 a setting of immune impainent cannot be rouled out.

5-04-05 Neurolues today A. Milicevic-Kalasic ‘, V. Mat-tic 2, J. llic ‘, T. Lepic2. ’ institute of GerontobgK Home Treatment and Care, Military Medical Academy Belgrade, Yugoslavia, ‘Clinic of neurology; Military Medical Academy, Belgrade, Yugoslavia

In spite of assumption that lues is eradicated all over the world our reported denies it. This paper has attention to present two cases with neurolues: one with acquired and the other one with congenital neurolues.

The first case report reefers on 44 year old man with these main complaints: painful lumbar syndrome, myopathy and encephalopathia. Per anamnesis it is found out that lues was diagnosed in his seventies with positive VDRL reaction.

The second one is dealing with 82 years old women with visual illusions, impairment of joint position function, convulsions, present Argyl-Robertson sign, Charwt joint and gummas in her clinical feature. As previous patient she was diagnosed by VDRL and Nelson test also. There is date that her father was treated as luetic patient.

l-x-l 5 04 06 Profile of cellular immune reponse among HAWISP patients in Rio de Janeiro

R.B. Corrha, M. Puccioni-Sohler, S.A.P. Novis, M.S.P. Oliveira, M.S.M. Carvalho. HUCFFAJFRJ; INCA/MS; HEMOPEBJ, Rio de Janeiro, Brasil

ObJective: To analyze the profiles of cellular immune reponse in HAM/TSP patients correlating with the time of disease.

DeeignlMethods: Twenty HAMfTSP patients attending in a neurological center in Rio de Janeiro (HUCFWUFRJ) were analysed. The diagnosis was made based on WHO criteria. Patients were divided in two groups according to the time of disease: 8 patients with less than five years of disease and 12 with more than five years. Heparinized blood samples were collected and peripheral blood mononuclear cells were isolated by Ficoll - Hypaque gradi- ent centrifugation. Cells were labeled with the immunofluorescent monoclonal probes (CD4, CD8, CD3, CD19, CD45, CD25, HLADR). Lymphocytes subsets percentages were determined by cytofluorometric analysis.

Results: The average age was 49.5 years (24-66) in the first group and 58.3 years (44-75) in the second; average time of disease was 3 and 10.8 years respectively. There was one male in the first group and two in the second. The mean percentages of lymphocytes subsets in the two groups were respectively: CD4 - 370/o/43.58%, CD8 - 270/o/26.6%, CD3 - 83.9%/66.5%, CD19-12.6%/8.7%. CD45-67.5%/92.8%, CD25-34.6%/21.9%and HLADR - 33.6%/37.4%.

Discus&on: The results shows changes in the distribution of lymphocytes subsets in HAMfTSP patients suggesting immune activation. Elevated percent- age of CD25 in the group with less than 5 years of disease maybs an indicator of disease activity. No major other differences were observed in both groups as a result of the time of disease.

1 5-04-07 1 Activities of cathepsins B and L in peripheral blood of patients with human T-lymphotrophic virus type 1 (HTLV-l)-associated myelopathy

R. Sugihara, T. Kumamoto, H. Ueyama, M. Kondo, S. Nagao, T. Shigenaga, T. Tsuda. Third Department of Internal Medicine, Oira Medical University, Oita, Japan

Human T-lymphotrophic virus type 1 (HTLV-1) is the etiologic agent in a slowly progressive spastic paraparesis, known as HTLV-l-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). Despite association with several abnomal immune phenomena, the mechanism of neural tissue damage by its infection remains virtually obscure. We evaluated the levels of two lysosomal proteases, cathepsins Band L, in peripheral blood mononuclear cells (PBMCs) and serum from HAM patients.

PBMCs and sera were obtained from 7 patients with HAM (4 women and 3 men; age range, 36-76 years), 8 patients with other neurological diseases (ONDs), and 10 normal healthy controls. The diagnosis of HAM was based on the criteria of Osame and colleagues (1986). Anti-HTLV-1 antibody titers were elevated in the serum (256102,400 X) and cerebral spinal fluid (16-512 X) in all HAM patients. The activities of both proteases were assayed by the method of Barrett (1980).

The activities of cathepsins B and L in PBMCs of HAM patients were significantly higher compared with normal control (cathepsin B, p = 0.01; cathepsin L, p < O.OOi), while there was significant difference only in cathepsin L activities between HAM patients and OND patients (p = 0.005). There were no significant difference in the activities of both cathepsins in serum from each group.

This result suggests that cathepsins B and L in PBMCs may play a certain role in the inflammatory process or pathogenesis of HAMTTSP.

I 5 04 08 Cavernous sinus syndrome: A clinical comparison between mucormycosis and non-mucormycosis

Somsak Tiamkao’, Suthipun Jitpimolmard ‘, Verajit Chotmongkol ’ , Benjapom Nitinavakam *. ‘Division of Neurobg)! Department of Medicine, Khon Kaen Univefsi~ Khon Kaen, Thailand, *Department of Radiology. Faculty of Medicine, Khon Kaen Universitv, Khon Kaen, Thailand

Introduction: Cavernous sinus syndrome is a disorder characterized by paral- ysis of cranial nerve 3, 4, 6 and 5. Causes of this syndrome are infectious and non-infectious source, such as mucormycosis, bacteria and malignancy. Delay in diagnosis and improper management contributed to high mortality rate. We report cavernous sinus syndrome patients at Srinagarind Hospital for recogni- tion and clinical comparison between mucormycosis and non-mucormycosis.

Patient and Method: Review of patient charts from 1985 to 1994 at Sri- nagarind Hospital, Department of Medicine, Faculty of Medicine, Khon Kaen University, with sinus thrombosis.

Result: There were 25 patients, 9 male, 16 female, male to female ratio was 1:1.7, age range from 30-79 years, mean was 55.08 years. Common pre-