Chorea associated with anti-phospholipid antibodies: case report.

A seventeen year-old boy developed left sided chorea in a few days, subsequently involving the four limbs. Although he presented a marfanoid phenotype, genetic analysis of the Fibrillin 1 was normal. The genes for familial chorea and Huntington's disease were also negative. Biological tests showed normal serum homocystein, but revealed very high levels of anti-beta2-GP1 IgG, anticardiolipin and lupus anticoagulant, which remained at similar values for a period of over three months. Electroencephalogram and cerebral magnetic resonance imaging (MRI) showed no abnormalities. Brain PET-scan disclosed bilateral striatal hypermetabolism. The patient was treated with methylprednisolone and low dose of acetylsalicylic acid. He improved markedly after six weeks of treatment, and choreic movements disappeared completely after two months. A control PET-scan performed at this time showed reversion of striated hypermetabolism to a normal pattern. The pathogenic aspects of this relatively rare case of chorea are discussed.

Spinocerebellar ataxia types 1, 2, 3, and 6: disease severity and nonataxia symptoms.

OBJECTIVE: To identify factors that determine disease severity and clinical phenotype of the most common spinocerebellar ataxias (SCAs), we studied 526 patients with SCA1, SCA2, SCA3. or SCA6. METHODS: To measure the severity of ataxia we used the Scale for the Assessment and Rating of Ataxia (SARA). In addition, nonataxia symptoms were assessed with the Inventory of Non-Ataxia Symptoms (INAS). The INAS count denotes the number of nonataxia symptoms in each patient. RESULTS: An analysis of covariance with SARA score as dependent variable and repeat lengths of the expanded and normal allele, age at onset, and disease duration as independent variables led to multivariate models that explained 60.4% of the SARA score variance in SCA1, 45.4% in SCA2, 46.8% in SCA3, and 33.7% in SCA6. In SCA1, SCA2, and SCA3, SARA was mainly determined by repeat length of the expanded allele, age at onset, and disease duration. The only factors determining the SARA score in SCA6 were age at onset and disease duration. The INAS count was 5.0 +/- 2.3 in SCA1, 4.6 +/- 2.2 in SCA2, 5.2 +/- 2.5 in SCA3, and 2.0 +/- 1.7 in SCA6. In SCA1, SCA2, and SCA3, SARA score and disease duration were the strongest predictors of the INAS count. In SCA6, only age at onset and disease duration had an effect on the INAS count. CONCLUSIONS: Our study suggests that spinocerebellar ataxia (SCA) 1, SCA2, and SCA3 share a number of common biologic properties, whereas SCA6 is distinct in that its phenotype is more determined by age than by disease-related factors.

Scale for the assessment and rating of ataxia: development of a new clinical scale.

OBJECTIVE: To develop a reliable and valid clinical scale measuring the severity of ataxia. METHODS: The authors devised the Scale for the Assessment and Rating of Ataxia (SARA) and tested it in two trials of 167 and 119 patients with spinocerebellar ataxia. RESULTS: The mean time to administer SARA in patients was 14.2 +/- 7.5 minutes (range 5 to 40). Interrater reliability was high, with an intraclass coefficient (ICC) of 0.98. Test-retest reliability was high with an ICC of 0.90. Internal consistency was high as indicated by Cronbach's alpha of 0.94. Factorial analysis revealed that the rating results were determined by a single factor. SARA ratings showed a linear relation to global assessments using a visual analogue scale, suggesting linearity of the scale (p < 0.0001, r(2) = 0.98). SARA score increased with the disease stage (p < 0.001) and was closely correlated with the Barthel Index (r = -0.80, p < 0.001) and part IV (functional assessment) of the Unified Huntington's Disease Rating Scale (UHDRS-IV) (r = -0.89, p < 0.0001), whereas it had only a weak correlation with disease duration (r = 0.34, p < 0.0002). CONCLUSIONS: The Scale for the Assessment and Rating of Ataxia is a reliable and valid measure of ataxia, making it an appropriate primary outcome measure for clinical trials.

SPG3A is the most frequent cause of hereditary spastic paraplegia with onset before age 10 years.

Seven families with six different SPG3A mutations were identified among 106 with autosomal dominant hereditary spastic paraplegia (HSP). Two mutations were novel (T162P, C375R). SPG3A was twice as frequent as SPG4 in patients with onset before age 10 years (31.8%). Later onset was not observed. The phenotype was pure HSP, but disease duration was longer than in non-SPG3A/SPG4 patients, leading ultimately to greater handicap.

Second polar body inclusion results in diploid/triploid mixoploidy.

We report three cases with a typical diploid/triploid mixoploidy. Cytogenetic analysis showed a normal diploid karyotype in peripheral blood lymphocytes and a mixture of diploid and triploid cells in skin fibroblasts. We analysed microsatellite markers in patients blood lymphocytes and skin fibroblasts and compared the results with the microsatellite markers in the parents. The extra haploid set was in all three cases of maternal origin. In one case the markers were not very informative but in two cases pericentromeric markers showed a single dose of one paternal allele and a double dose of one maternal allele, more telomeric markers showed one paternal allele and two different maternal alleles. These observations can only be explained by the inclusion of the second polar body in one of the blastomeres at the cleavage stage.

Sialic acid residues in the labial salivary glands from Sjögren's syndrome patients.

OBJECTIVE: To investigate the composition and expression of sialic acid in the labial salivary glands (LSG) in Sjögren's syndrome (SS). METHODS: LSG of 19 patients with primary SS (n = 11) or secondary SS (n = 8) were studied. Specimens from 7 healthy women served as controls. Computer-assisted microscopy was employed to quantitatively determine the percentage of positive structures, the staining intensity and the heterogeneity for the 4 biotinylated plant lectins Tritricum vulgaris L. (WGA), Maackia amurensis (MAA), Sambucus nigra (SNA) and Canavalia ensiformis L. (Con A). RESULTS: In the acini there was a significant decrease in the staining heterogeneity of WGA in SS compared to controls; the same was observed with respect to MAA staining in the connective tissue and extralobular ducts. In the intralobular ducts, primary SS differed from normal and secondary SS mainly in terms of a decrease in the percentage of positively labeled MAA tissue. In addition, Con A stained acinar cells were significantly more numerous in secondary SS compared with primary SS. CONCLUSION: Differences in the degree of glycoconjugate sialylation were found in SS labial salivary glands, and may play a role in the disease process.

D-mannose and N-acetylglucosamine moieties and their respective binding sites in salivary glands of Sjögren's syndrome.

OBJECTIVE: Sjögren's syndrome (SS) is an autoimmune exocrinopathy. The mannose binding lectin (MBL), a pluripotent molecule of the innate immune system, is involved in the pathogenesis of autoimmune diseases. We investigated whether specific ligands for MBL and MBL related structures could be reliable markers in cases of SS. METHODS: The labial salivary glands of 19 patients fulfilling the diagnostic criteria for primary (n=11) and secondary SS (n=8) were studied. Seven healthy women served as controls. Computer assisted microscopy was employed to determine quantitatively the percentage of positive structures (acini, ducts, and interlobular connective tissue), the staining intensity, and the level of staining heterogeneity for 4 glycohistochemical probes including wheat germ agglutinin and concanavalin (Con A) as lectins, and mannose and N-acetylglucosamine as parts of neoglycoproteins. The data were evaluated by discriminant analysis. RESULTS: The data strongly suggest that MBL related structures, if not MBL itself, could play distinct roles in the pathogenesis of primary versus secondary SS. Further, quantitative determination of the level of expression of D-mannose and N-acetylglucosamine and their respective binding sites in labial salivary gland acini offers a powerful diagnostic tool for distinguishing primary from secondary SS. CONCLUSION: In SS labial salivary glands, determination of the level of acceptor sites for wheat germ agglutinin, Con A, D-mannose, and N-acetylglucosamine provides information on the roles played by glycoforms in SS. The methodology and data described in this paper should provide pathologists with objective diagnostic markers for SS. Our results should enhance the biological understanding of this pathology.