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4-13-02 Adult onset globoid cell leukodystrophy (Krabbe disease): Analysis of galactosylceramidase cDNA from four Japanese patients
S228
Demyelinating
4-l 2-09
J. Preuss,
Diseases, other than Multiple
Temporal and spatial orientation associated with mental and written calculation In primarv - coanitive deterioration A. Goldfarb,
D. De Cinti. Hospital
Franc&,
Buenos
4-13-02
Aires, Argentina
Objective: The purpose of the present study was to establish the association of Temporal and Spatial Orientation (TO), (SO) with Mental and Written Calculation (MC), (WC) in a sample with different degrees of Primary Cognitive Deterioration according to Alzheimer’s model. Method: A sample of 134 subjects was scored by Reisberg’s GDS, DSM Ill-R criteria for Dementia and NINCDS-ADRDA criteria for Primary Degenerative Dementia of the Alzheimer type. The scores on the items TO, SO and MC (by serial substraction test) of the Folstein Mini Mental State Examination (MMSE) and WC in accordance with the Luda protocols were analysed. Results: The mean age of the subjects was 68.88 +- 10.18 and 84% were female. The strong association between GDS and the different items was previously established (in 1994) by Spearman’s linear correlation coefficient, rT0, SO/GDS = 0.72 and rMC, WC/GDS = 0.70. In this study, the correlation between the different tests was rTO/WC = 0.96, rTO/MC = 0.61, rSO/MC = 0.52 and rSOMlC = 0.47, all of them significant with p < 0.01. Conclusions: As Cognitive Deterioration increases, there is a linear and proportional decrease in Mental and Written Calculation as well as in Temporal and Spatial Orientation, Temporal Orientation showing not only a greater impairment but the strongest correlation with the Written Calculation impairment (Acalculia). The strong association between these two items which are related by the implication of an impairment in numerical operations shows a research pathway not sufficiently explored in the study of Dementia, and is better evidence of this neuropsychological disorder so frequent in Cognitive Deterioration,
Progressive multifocal leukoencephalopathy hivlaids child - Case report
of for
We examined galactosylceramidase (GALC) cDNA in four Japanese patients with adult onset globoid cell leukodystrophy (Krabbe disease) (AO-GLD) by PCR-SSCP analysis, subsequent sequence determination, and restriction enzyme digestion of PCR products. Initial symptoms were the onset of slowly progressive spastic paraplegia from the middle second decade, and all patients had diminished GALC activity in their leukocytes. We identified three missense mutations (166M, G270D, L618S) and one exon 6 skipping (535-573 del). Two of the patients had only the l66M mutant mRNA, and one only the G270D mutant mRNA. The fourth patient carried a compound heterozygous mutation of 535-573 del and L618S. To determine enzymatic activities produced by these mutations, we constructed mutated GALC cDNAs and expressed them in COS-I cells. Three mutations (G270D, L618S, and exon 6 skipping (535-573 del)) produced diminished GALC activity as expected. The l66M mutation in the wild type GALC cDNA (1289) had normal activity, but when this mutation and V289 polymorphism were introduced into the same allele, it had decreased activity. These findings show that the combination of an unique mutation and polymorphism caused conformational change in the GALC enzyme, resulting in low enzymatic activity. AO-GLD mutations, including those found here, are located in the N (166M, G270D, 535-573 del) or C (L618S) terminus of the GALC enzyme. Whereas the reported mutations in the infantile form (IF-GLD) are in the central domain. This difference in mutation sites may affect the phenotype of the clinical features of GLD.
Pathogenesis
of Behcet’s disease
T. Lehner, A. Hasan, A. Wilson, W. Hu, M. Stanford, Y. Li. Deptof Immunology United Medical & Dental Schools of Guy3 & St Thomas’ Hospitals, London SE7 9RT England
Demyelinating Diseases, other than Multiple Sclerosis
I4 13 01
Adult onset globoid cell leukodystrophy (Krabbs disease): Analvsis of aalactosvlceramldase cDNA from four Japanese pitients -
H. Furuya, Y. Kukita ‘, S. Nagano, K. Hayashi I, T. Kobayashi. Department Neurology, Neurological Institute, Facu/ty of Medicine, ’ Research institute Genetic Information, Kyushu University 60, Fukuoka, Japan
4-13-03
13
Sclerosis
in
S. Alves, R. Nunes, A. Kropf, B. Silveira, R. Alvarenga, J. Marcondes, N. Rubini, H. Alvarenga. Universidade do Rio de Janeiro, Hospital G&free Guinle (HUGG), Brazil
e
Obfective: Report one rare case of neurological manifestation (NM) in hiv/aids child, associated to an atypical beginning o!nervous system (NS) assault. Method/Case Report: J.A.B.M, 12 years old, male, white, infected by vertical transmission. Until NS attack presented 02 episodes of oral candid&es, diarrhea, asthenia, and persistent dermatitis. In November 95, presented partial motor seizure with clonic activity of lower limb. progressed after one week with right crural monoparesis. CT showed two low density nonenhancing areas, no mass effect, in left frontal and paracentral lobes. CSF was normal. CDC/92 A3 (CD4 < 200) MRI in December/95 showed two small areas of high intensity in T2 and low sigh in Tl , located in left frontal lobe with nonenhancing areas. Needle biopsy was indicated but postponed due to the clinical improvement by the use of corticosteroids. Two months later he developed spastic paraplegia and right monoparesis on upper limb. MRI March/96 showed progression of white matter lesions with the same characteristics of the one made in December/95, attacking the adjacent area of left ventricle and new areas in interne capsule, no mass effect. CSF was normal. The biopsy in March/96 with CT confirmed PML. Immunological competence: CD3 PAN - 367; CD4 - 9; CD8 358; CD4/CD8 - 80.03: 82 microglobulin - 3.7; p24 - negative. The patient progressed tetraplegic and in superficial coma. Pulsotherapy with ARA C made him gets better in the beginning of treatment but then in May 96 he died after a digestive bleeding. Conclusions: PML is rare in child. Lesions involving gray matter in PML and seizure as initial manifestation are rares. It is probable that the establish of PML in this child keep relation to the opportunistic characteristic of JC virus often associated to lower count of CD4 eels (cd4 < 200) as on this report.
Behcet’s disease (BD) is a multisystem disorder, the diagnosis of which is based on a set of international clinical criteria. The aetiology and immunopathology of BD has been associated with herpes simplex virus, autoimmunity to oral mucosa or cross-reactivity with microbial antigens. Some of these aetiological factors might have a common denominator in microbial stress or heat shock protein (HSP) which shows significant homology with the human mitochondrial HSP. Indeed, the uncommon serotypes of Sfreptoccccus sang& found in BD cross-react with the 65 kDa HSP which also shares antigenicity with an oral mucosal antigen. T cell epitope mapping has identified 4 peptides derived from the sequence of the 65 kDa HSP which have significant homology with the corresponding peptides derived from the human 60 kDa HSP. They stimulate specifically TCR-ya+ lymphocytes from patients with BD and the lymphoproliferative response elicited by the 4 peptides can be used as a diagnostic test of BD. The pathogenic significance of these peptides has been established by inducing uveitis in rats. The most effective peptide is the human 60 kDa HSP derived sequence aa 336-351 which can elicit uveitis by subcutaneous, oral or nasal administration. The finding of peptides specific in Behcet’s disease and the development of an animal model, with at least one major manifestation of the disease, enable us to investigate the immunotherapeutic potential of monoclonal antibodies to T cell surface antigens and cytokines.
4-13-04
Correlation between neurologic manifestations and brain MRI appearances in vitamin 812 deficiency
2. Levi& N. Stojsavljevic, J. Drulovic, Neufolog)! Clinical Center of Serbia, Belgrade, Yugoslavia
V. Peric, G. Dragutinovic. lnsfitute School of Medicine, Universify of
of
Brain magnetic resonance imaging (MRI) findings in patients with vitamin 812 deficiency has received little attention. We report the MRI data of 6 patients with 812 deficiency who presented with various neurologic manifestations. There were 7 women and one man, aged 35-68 years. MRI was performed 3 months to 12 years after the appearance of neurologic symptoms, prior to administration of hydroxocobalamin. Three patients had combination of signs of cerebral involvement (Cl), myelopathy and polyneuropathy, one had combination of Cl, myelopathy and myopathy, one combination of myelopathy and polyneuropathy, one Cl and polyneuropathy, one had exclusively signs of Cl and one of myopathy. Six patients had multiple focal and confluent TP-weighted white matter hyperintensities on brain MRI. In a patient with myopathy and in patient with Cl, myelopathy and myopathy, in whom neurologic symptoms lasted four months, Brain MRI was normal. Our findings suggest that white matter changes on brain MRI may be frequent in patients who have signs of central nervous system involvement due to B12 deficiency.
Demyelinating
4-l 2-09
J. Preuss,
Diseases, other than Multiple
Temporal and spatial orientation associated with mental and written calculation In primarv - coanitive deterioration A. Goldfarb,
D. De Cinti. Hospital
Franc&,
Buenos
4-13-02
Aires, Argentina
Objective: The purpose of the present study was to establish the association of Temporal and Spatial Orientation (TO), (SO) with Mental and Written Calculation (MC), (WC) in a sample with different degrees of Primary Cognitive Deterioration according to Alzheimer’s model. Method: A sample of 134 subjects was scored by Reisberg’s GDS, DSM Ill-R criteria for Dementia and NINCDS-ADRDA criteria for Primary Degenerative Dementia of the Alzheimer type. The scores on the items TO, SO and MC (by serial substraction test) of the Folstein Mini Mental State Examination (MMSE) and WC in accordance with the Luda protocols were analysed. Results: The mean age of the subjects was 68.88 +- 10.18 and 84% were female. The strong association between GDS and the different items was previously established (in 1994) by Spearman’s linear correlation coefficient, rT0, SO/GDS = 0.72 and rMC, WC/GDS = 0.70. In this study, the correlation between the different tests was rTO/WC = 0.96, rTO/MC = 0.61, rSO/MC = 0.52 and rSOMlC = 0.47, all of them significant with p < 0.01. Conclusions: As Cognitive Deterioration increases, there is a linear and proportional decrease in Mental and Written Calculation as well as in Temporal and Spatial Orientation, Temporal Orientation showing not only a greater impairment but the strongest correlation with the Written Calculation impairment (Acalculia). The strong association between these two items which are related by the implication of an impairment in numerical operations shows a research pathway not sufficiently explored in the study of Dementia, and is better evidence of this neuropsychological disorder so frequent in Cognitive Deterioration,
Progressive multifocal leukoencephalopathy hivlaids child - Case report
of for
We examined galactosylceramidase (GALC) cDNA in four Japanese patients with adult onset globoid cell leukodystrophy (Krabbe disease) (AO-GLD) by PCR-SSCP analysis, subsequent sequence determination, and restriction enzyme digestion of PCR products. Initial symptoms were the onset of slowly progressive spastic paraplegia from the middle second decade, and all patients had diminished GALC activity in their leukocytes. We identified three missense mutations (166M, G270D, L618S) and one exon 6 skipping (535-573 del). Two of the patients had only the l66M mutant mRNA, and one only the G270D mutant mRNA. The fourth patient carried a compound heterozygous mutation of 535-573 del and L618S. To determine enzymatic activities produced by these mutations, we constructed mutated GALC cDNAs and expressed them in COS-I cells. Three mutations (G270D, L618S, and exon 6 skipping (535-573 del)) produced diminished GALC activity as expected. The l66M mutation in the wild type GALC cDNA (1289) had normal activity, but when this mutation and V289 polymorphism were introduced into the same allele, it had decreased activity. These findings show that the combination of an unique mutation and polymorphism caused conformational change in the GALC enzyme, resulting in low enzymatic activity. AO-GLD mutations, including those found here, are located in the N (166M, G270D, 535-573 del) or C (L618S) terminus of the GALC enzyme. Whereas the reported mutations in the infantile form (IF-GLD) are in the central domain. This difference in mutation sites may affect the phenotype of the clinical features of GLD.
Pathogenesis
of Behcet’s disease
T. Lehner, A. Hasan, A. Wilson, W. Hu, M. Stanford, Y. Li. Deptof Immunology United Medical & Dental Schools of Guy3 & St Thomas’ Hospitals, London SE7 9RT England
Demyelinating Diseases, other than Multiple Sclerosis
I4 13 01
Adult onset globoid cell leukodystrophy (Krabbs disease): Analvsis of aalactosvlceramldase cDNA from four Japanese pitients -
H. Furuya, Y. Kukita ‘, S. Nagano, K. Hayashi I, T. Kobayashi. Department Neurology, Neurological Institute, Facu/ty of Medicine, ’ Research institute Genetic Information, Kyushu University 60, Fukuoka, Japan
4-13-03
13
Sclerosis
in
S. Alves, R. Nunes, A. Kropf, B. Silveira, R. Alvarenga, J. Marcondes, N. Rubini, H. Alvarenga. Universidade do Rio de Janeiro, Hospital G&free Guinle (HUGG), Brazil
e
Obfective: Report one rare case of neurological manifestation (NM) in hiv/aids child, associated to an atypical beginning o!nervous system (NS) assault. Method/Case Report: J.A.B.M, 12 years old, male, white, infected by vertical transmission. Until NS attack presented 02 episodes of oral candid&es, diarrhea, asthenia, and persistent dermatitis. In November 95, presented partial motor seizure with clonic activity of lower limb. progressed after one week with right crural monoparesis. CT showed two low density nonenhancing areas, no mass effect, in left frontal and paracentral lobes. CSF was normal. CDC/92 A3 (CD4 < 200) MRI in December/95 showed two small areas of high intensity in T2 and low sigh in Tl , located in left frontal lobe with nonenhancing areas. Needle biopsy was indicated but postponed due to the clinical improvement by the use of corticosteroids. Two months later he developed spastic paraplegia and right monoparesis on upper limb. MRI March/96 showed progression of white matter lesions with the same characteristics of the one made in December/95, attacking the adjacent area of left ventricle and new areas in interne capsule, no mass effect. CSF was normal. The biopsy in March/96 with CT confirmed PML. Immunological competence: CD3 PAN - 367; CD4 - 9; CD8 358; CD4/CD8 - 80.03: 82 microglobulin - 3.7; p24 - negative. The patient progressed tetraplegic and in superficial coma. Pulsotherapy with ARA C made him gets better in the beginning of treatment but then in May 96 he died after a digestive bleeding. Conclusions: PML is rare in child. Lesions involving gray matter in PML and seizure as initial manifestation are rares. It is probable that the establish of PML in this child keep relation to the opportunistic characteristic of JC virus often associated to lower count of CD4 eels (cd4 < 200) as on this report.
Behcet’s disease (BD) is a multisystem disorder, the diagnosis of which is based on a set of international clinical criteria. The aetiology and immunopathology of BD has been associated with herpes simplex virus, autoimmunity to oral mucosa or cross-reactivity with microbial antigens. Some of these aetiological factors might have a common denominator in microbial stress or heat shock protein (HSP) which shows significant homology with the human mitochondrial HSP. Indeed, the uncommon serotypes of Sfreptoccccus sang& found in BD cross-react with the 65 kDa HSP which also shares antigenicity with an oral mucosal antigen. T cell epitope mapping has identified 4 peptides derived from the sequence of the 65 kDa HSP which have significant homology with the corresponding peptides derived from the human 60 kDa HSP. They stimulate specifically TCR-ya+ lymphocytes from patients with BD and the lymphoproliferative response elicited by the 4 peptides can be used as a diagnostic test of BD. The pathogenic significance of these peptides has been established by inducing uveitis in rats. The most effective peptide is the human 60 kDa HSP derived sequence aa 336-351 which can elicit uveitis by subcutaneous, oral or nasal administration. The finding of peptides specific in Behcet’s disease and the development of an animal model, with at least one major manifestation of the disease, enable us to investigate the immunotherapeutic potential of monoclonal antibodies to T cell surface antigens and cytokines.
4-13-04
Correlation between neurologic manifestations and brain MRI appearances in vitamin 812 deficiency
2. Levi& N. Stojsavljevic, J. Drulovic, Neufolog)! Clinical Center of Serbia, Belgrade, Yugoslavia
V. Peric, G. Dragutinovic. lnsfitute School of Medicine, Universify of
of
Brain magnetic resonance imaging (MRI) findings in patients with vitamin 812 deficiency has received little attention. We report the MRI data of 6 patients with 812 deficiency who presented with various neurologic manifestations. There were 7 women and one man, aged 35-68 years. MRI was performed 3 months to 12 years after the appearance of neurologic symptoms, prior to administration of hydroxocobalamin. Three patients had combination of signs of cerebral involvement (Cl), myelopathy and polyneuropathy, one had combination of Cl, myelopathy and myopathy, one combination of myelopathy and polyneuropathy, one Cl and polyneuropathy, one had exclusively signs of Cl and one of myopathy. Six patients had multiple focal and confluent TP-weighted white matter hyperintensities on brain MRI. In a patient with myopathy and in patient with Cl, myelopathy and myopathy, in whom neurologic symptoms lasted four months, Brain MRI was normal. Our findings suggest that white matter changes on brain MRI may be frequent in patients who have signs of central nervous system involvement due to B12 deficiency.