2
Poster Abstracts Tuesday, November 8, 2005 $275 Prado, SS ~, Godoy, AJ ~, Faccio, AA ~. 1University ofRibeirao Preto, Ribeirao Preto, Brazil Background: There are reports of alitilieurolial antibodies (such as attti-Ri) in patients with neurological paralieoplastic syndromes, including memory deficits. We decided to check the occurrence of autoantibodies in patients with malignant neoplasms and their ability to recognize faces. Method: We selected 16 patients with malignant neoplasms: gyneco- logical tumors (11), lymphoma (1), gastric carcinomas (12), larynx tumor (1) and thyroid carcinoma (1). None of them underwent chemotherapy. Twelve had their tumors surgically removed withJli the last five years. A group control was carefully chosen. Standardized memory tests for face recognition were performed. All subjects had their sera checked by the presence of antinuclear antibodies. Selected sera will be sent to the Nichols Laboratory for further alialysis. Results: All of our subjects were younger than 60 years. Except for the memory deficit, none of the patients showed neurological abnormalities. We found a statistically significant difference between the memory tests" scores: The patients got, on average, 8.99 (of a maximum 13.00) and the controls scored 10.65 (Maliii- Whitney test, p < 0.0014). Two patients had a positive alitiliuclear antibody test. Conclusion: Patients with malignant neoplasms may have an impair- ment of the recognition memory for faces. This cerebral function depends on both hemispheres and some antineuronal antibodies related to neoplasms could recognize widely distributed nerve cells antigens. The IItelitory deficit may be found even years after the surgical removal of the tulitor. We hypothesize that solite tulitor cells antigens could trigger an immune response important for the development of a memory dysfunction. 0691 Characterization of ndcroglia induced from mouse embryotfic stem cells and their migration into the brain parenchyma. Shimizu, K ~, Tsuclfiya, T 1 , Masahira, N 1 , Chang, P, K 1, Toyonaga, S ~, Yamada, M ~, Nakabayashi, H l, Nakai, E 1 . 1Department of Neurosurgery, R~ehi Medical School, Koehi University Background: Microglia is very similar to peripheral macrophage, and exist at central nervous system (CNS). Microglia function as an antigen presenting cell in several CNS diseases, but the detailed mechanism has remained obscure yet Microglial progenitor or precursor cells have been not identified. Method: We derived IIlicroglia froli1 mouse elmbryordc stem cells (ES cells) at very high density. Using the markers Macl+/ CD451°~ and Macl+/CD455xgh to define lrdcroglia and macrophages, respectively, we show that Macl positive cells are induced by GM-CSF stimulation following neuronal differentiation of mouse ES cells using a five-step method. Results: CD45 l°W expression was high and CD45 t~h expression was low on induced cells. We used a density gradient IIlethod to obtain a large alitoulit of microglia-like cells, approximately 90 % of Macl + cells. Microglia-like cells expressed MHC class I, class II, CD40, CDS0, CD86, and IFN-5"R. The expression level of these molecules on rnicroglia-like cells was barely enhanced by IFN-% Intravenously transferred GFP + lrdcroglia derived fioli1 GFP + ES cells selectively accalimlated in brain but not in peripheral tissues such as spleen and lymph node. GFP + cells were detected mainly in corpus callosum and hippocampus but were rarely seen in cerebral cortex, where Ibal, another marker of microglia, is primarily expressed. Further- more, both GFP + and Ibal + cells exhibited a ramified morphology characteristic of mature rnicroglia. Conclusion: Titus, we suggest that mature microglia induced with our protocol may function as braili-specific delivery of medicines, or other bioactive materials, such as proteins or genes 0692 Passive transfer of conduction block and demyelination by sera from Chronic Inflanmlatory Demyelinating Polyradiculonettropathy patients Tseng, C 1, Wang, M z, Pollard, j3 :Department of Neurology, China Medical University Hospital, and School of Medicine, China; 2Medical University, Taiehung, Taiwan; 3Department of Neurology, Royal Prince Alfred Hospital, and Institute of Clinical Neuroseienee, University of Sydney, Sydney, Australia Background: Chronic iliflaliuliatory demyeliliatilig polyradiculolieuro- pathy (CIDP) is generally considered to be an autoilimmlie disorder, though the defined autoimmune mechanism remains unknown. The demyelniation in CIDP may be associated with antibodies to myelin proteins or other Schwann cell antigens, as most patients respond to plasma exchange. The current study was designed to investigate 1) the presence of alitibodies to myelin proteins in patients with CIDP; 2) the pathological roles of these antibodies in CIDP. Methods: Sera from 10 CIDP patients were examined by indirect immunofluorescence (IF) for anti-myelin antibodies using normal nerve as a substrate. Sera from 6 patients positive for anti-myelni antibodies were injected to tibial branches of sciatic nerves of Lewis rats and subsequent IIeurophysiological studies were followed at Day 3, 5, 7, 10, 12, 14, 17, 20 after injection. Western blot analysis was perforliled to colifirli1 the serum binding activity to myelin protein. Results: Six sera out 10 sera tested were positive for anti-myelin activity detected by IF techniques. Rats received intraneural injection of the positive sera all presented marked conduction block (at day 3, 5, 7 post-ilijectioli) and demyeliliatioli (at day 5, 7, 10 post-ilijectioli). Control rats injected with either normal sera or sera from CIDP patients negative for aliti-iilyelili antibodies showed IIomlal IIeuro- physiology and no demylination. Contusion: Results from current study suggest that anti-myelin/ Schwaliii cell autoalitibodies IItay play an important role in the pathogeliesis of CIDP at least in some patients. 0693 Inflammatory Myelopathy: A clinical entity strongly associated to Antiphospholipid Antibodies Valdbs-Ferrer, S l, D~vila, L ~, Garcia Ramos, G 1 . llnstituto Nacional De Ciencias MOdicas Y Nutricidn SZ, Mexico City, Mexico Heading: We present a retrospective series of patients with Myelitis, their clinical features and outcomes, and its strong association with Antiphospholipid antibodies (aAPL). Background: Inflamatory Myelitis is a rare complication of Systemic Lupus Erythematosus (SLE), Sjrgreli's syndrome and other autoimmulie diseases. Its mechmfism has not been elucidated, but alitiphosphlipid antibodies appear to have a pathophysiological role beyond the well known prothrombotic mecharfism. Method: We retrospectively sought patients with inflammatory non- infectious Myelopathies. Traumatic., ischemic or neoplastic, cases were excluded. A series of cases are reported, including their clinical features, aAPL status, and outcomes according to treatment and degree of involvement (catastrophic or IIoli-catastrophic). Results: 29 episodes of Myelopathy were analyzed; 27 in SLE-patielits and 2 in non-SLE patients. Two patients on the SLE group had recurrent myelopathy. Non-SLE patients had monoepisodic myelopathy developing early in the course of disease. In the SLE group 60% had Myelitis wittfili the first 5 years of disease. In the SLE branch, 21 cases were catastrophic in presentation (unable to perform an independent life). None died as a direct consecuence of myelopathy. All but one tested positive for aAPL. In contrast, the non- SLE patients had a more severe involvement, and one died due zto expansion of Myelitis to the brainstem. Both patients tested positive for aAPL. Conclusion: aAPL were positive in all but one of our patients. Tiffs suggests a prominent role of the aAPL; its mechmfisms may well be

0694 The polymorphism of HLA-DRB1 in Chinese child-onset myasthenia gravis

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Page 1: 0694 The polymorphism of HLA-DRB1 in Chinese child-onset myasthenia gravis

Poster Abstracts Tuesday, November 8, 2005 $275

Prado, SS ~, Godoy, AJ ~, Faccio, AA ~. 1University ofRibeirao Preto, Ribeirao Preto, Brazil

Background: There are reports of alitilieurolial antibodies (such as attti-Ri) in patients with neurological paralieoplastic syndromes, including memory deficits. We decided to check the occurrence of autoantibodies in patients with malignant neoplasms and their ability to recognize faces. Method: We selected 16 patients with malignant neoplasms: gyneco- logical tumors (11), lymphoma (1), gastric carcinomas (12), larynx tumor (1) and thyroid carcinoma (1). None of them underwent chemotherapy. Twelve had their tumors surgically removed withJli the last five years. A group control was carefully chosen. Standardized memory tests for face recognition were performed. All subjects had their sera checked by the presence of antinuclear antibodies. Selected sera will be sent to the Nichols Laboratory for further alialysis. Results: All of our subjects were younger than 60 years. Except for the memory deficit, none of the patients showed neurological abnormalities. We found a statistically significant difference between the memory tests" scores: The patients got, on average, 8.99 (of a maximum 13.00) and the controls scored 10.65 (Maliii- Whitney test, p < 0.0014). Two patients had a positive alitiliuclear antibody test. Conclusion: Patients with malignant neoplasms may have an impair- ment of the recognition memory for faces. This cerebral function depends on both hemispheres and some antineuronal antibodies related to neoplasms could recognize widely distributed nerve cells antigens. The IItelitory deficit may be found even years after the surgical removal of the tulitor. We hypothesize that solite tulitor cells antigens could trigger an immune response important for the development of a memory dysfunction.

0691 Characterization of ndcroglia induced from mouse embryotfic stem cells and their migration into the brain parenchyma.

Shimizu, K ~, Tsuclfiya, T 1 , Masahira, N 1 , Chang, P, K 1, Toyonaga, S ~, Yamada, M ~, Nakabayashi, H l, Nakai, E 1 . 1Department of Neurosurgery, R~ehi Medical School, Koehi University

Background: Microglia is very similar to peripheral macrophage, and exist at central nervous system (CNS). Microglia function as an antigen presenting cell in several CNS diseases, but the detailed mechanism has remained obscure yet Microglial progenitor or precursor cells have been not identified. Method: We derived IIlicroglia froli1 mouse elmbryordc stem cells (ES cells) at very high density. Using the markers Macl+/ CD451°~ and Macl+/CD455xgh to define lrdcroglia and macrophages, respectively, we show that Macl positive cells are induced by GM-CSF stimulation following neuronal differentiation of mouse ES cells using a five-step method. Results: CD45 l°W expression was high and CD45 t~h expression was low on induced cells. We used a density gradient IIlethod to obtain a large alitoulit of microglia-like cells, approximately 90 % of Macl + cells. Microglia-like cells expressed MHC class I, class II, CD40, CDS0, CD86, and IFN-5"R. The expression level o f these molecules on rnicroglia-like cells was barely enhanced by IFN-% Intravenously transferred GFP + lrdcroglia derived fioli1 GFP + ES cells selectively accalimlated in brain but not in peripheral tissues such as spleen and lymph node. GFP + cells were detected mainly in corpus callosum and hippocampus but were rarely seen in cerebral cortex, where Ibal , another marker of microglia, is primarily expressed. Further- more, both GFP + and Ibal + cells exhibited a ramified morphology characteristic of mature rnicroglia. Conclusion: Titus, we suggest that mature microglia induced with our protocol may function as braili-specific delivery of medicines, or other bioactive materials, such as proteins or genes

0692 Passive transfer of conduction block and demyelination by sera from Chronic Inflanmlatory Demyelinating Polyradiculonettropathy patients

Tseng, C 1, Wang, M z, Pollard, j 3 :Department of Neurology, China Medical University Hospital, and School of Medicine, China; 2Medical University, Taiehung, Taiwan; 3Department of Neurology, Royal Prince Alfred Hospital, and Institute of Clinical Neuroseienee, University of Sydney, Sydney, Australia

Background: Chronic iliflaliuliatory demyeliliatilig polyradiculolieuro- pathy (CIDP) is generally considered to be an autoilimmlie disorder, though the defined autoimmune mechanism remains unknown. The demyelniation in CIDP may be associated with antibodies to myelin proteins or other Schwann cell antigens, as most patients respond to plasma exchange. The current study was designed to investigate 1 ) the presence of alitibodies to myelin proteins in patients with CIDP; 2) the pathological roles of these antibodies in CIDP. Methods: Sera from 10 CIDP patients were examined by indirect immunofluorescence (IF) for anti-myelin antibodies using normal nerve as a substrate. Sera from 6 patients positive for anti-myelni antibodies were injected to tibial branches of sciatic nerves of Lewis rats and subsequent IIeurophysiological studies were followed at Day 3, 5, 7, 10, 12, 14, 17, 20 after injection. Western blot analysis was perforliled to colifirli1 the serum binding activity to myelin protein. Results: Six sera out 10 sera tested were positive for anti-myelin activity detected by IF techniques. Rats received intraneural injection of the positive sera all presented marked conduction block (at day 3, 5, 7 post-ilijectioli) and demyeliliatioli (at day 5, 7, 10 post-ilijectioli). Control rats injected with either normal sera or sera from CIDP patients negative for aliti-iilyelili antibodies showed IIomlal IIeuro- physiology and no demylination. Contusion: Results from current study suggest that anti-myelin/ Schwaliii cell autoalitibodies IItay play an important role in the pathogeliesis o f CIDP at least in some patients.

0693 Inflammatory Myelopathy: A clinical entity strongly associated to Antiphospholipid Antibodies

Valdbs-Ferrer, S l, D~vila, L ~, Garcia Ramos, G 1 . llnstituto Nacional De Ciencias MOdicas Y Nutricidn SZ, Mexico City, Mexico

Heading: We present a retrospective series of patients with Myelitis, their clinical features and outcomes, and its strong association with Antiphospholipid antibodies (aAPL). Background: Inflamatory Myelitis is a rare complication of Systemic Lupus Erythematosus (SLE), Sjrgreli's syndrome and other autoimmulie diseases. Its mechmfism has not been elucidated, but alitiphosphlipid antibodies appear to have a pathophysiological role beyond the well known prothrombotic mecharfism. Method: We retrospectively sought patients with inflammatory non- infectious Myelopathies. Traumatic., ischemic or neoplastic, cases were excluded. A series of cases are reported, including their clinical features, aAPL status, and outcomes according to treatment and degree of involvement (catastrophic or IIoli-catastrophic). Results: 29 episodes of Myelopathy were analyzed; 27 in SLE-patielits and 2 in non-SLE patients. Two patients on the SLE group had recurrent myelopathy. Non-SLE patients had monoepisodic myelopathy developing early in the course of disease. In the SLE group 60% had Myelitis wittfili the first 5 years of disease. In the SLE branch, 21 cases were catastrophic in presentation (unable to perform an independent life). None died as a direct consecuence of myelopathy. All but one tested positive for aAPL. In contrast, the non- SLE patients had a more severe involvement, and one died due zto expansion of Myelitis to the brainstem. Both patients tested positive for aAPL. Conclusion: aAPL were positive in all but one of our patients. Tiffs suggests a prominent role of the aAPL; its mechmfisms may well be

Page 2: 0694 The polymorphism of HLA-DRB1 in Chinese child-onset myasthenia gravis

$276 Tuesday, November 8, 2005 Poster Abstracts

beyond ischemic-mediated damage, suggesting a direct inf lammatory damage inflicted to neurons or its fibers.

0694 Tile Polymorphisnl of HLA-DRB1 in Chinese child-onset Nlyasthenia G~avis

Zhao, C, Lu, C. Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China

Myasthenia gravis is a common auto immune disorder in Chinese clffldren, the incidence is superior to Caucasus and it differs a lot from adult-onset patients. To investigate whether HLA-DRBI polymorph- ism correlates with the marked heterogeneity of Chinese child-onset MG, the polymerase chain reaction/sequence specific primers(PCR/ SSP) was used to analyze the HLA-DRB1 alleles in 29 cases of adult- onset MG, 44 cases of child-onset M G and 45 cases of normal

individuals. The allele '0901 was found to have a higher frequency in child-onset patients when compared with controls (p < 0.005, OR -- 4.067) and adult-onset M G (p < 0.01, OR -- 4.135), which indicated that tiffs allele reported correlated with Chinese M G previously is actually correlated with child-onset MG. Furthermore, '0701-0702 alleles might has a negative correlation with child-onset M G (i3 - 0.024), but more samples still need to be investigated. To explore the correlation between '0901 and different clinic features of Chinese child-onset MG, 44 cases of children with M G were analyzed. "0901 was just found correlated with young age of onset rather than with sex, clinical type, serum AchR-ab and PsmR-ab. Accordingly, it was concluded that child-onset M G m a y differ from adult-onset M G in genetic background, and we also suspected that the different H L A genetic background might contribute to the different inddence of child-onset M G in Chinese and Caucasus population.