Corticospinal Tract Injury Precedes Thalamic Volume Reduction in Preterm Infants with Cystic Periventricular Leukomalacia.

OBJECTIVES: To measure both fractional anisotropy (FA) values in the corticospinal tracts (CSTs) and volume of the thalami in preterm infants with cystic periventricular leukomalacia (c-PVL) and to compare these measurements with control infants. STUDY DESIGN: Preterm infants with c-PVL and controls with magnetic resonance imaging data acquired between birth and term equivalent age (TEA) were retrospectively identified in 2 centers. Tractography of the CST and segmentation of the thalamus were performed, and values from infants with c-PVL and controls were compared. RESULTS: Thirty-three subjects with c-PVL and 31 preterm controls were identified. All had at least 1 scan up to TEA, and multiple scans were performed in 31 infants. A significant difference in FA values of the CST was found between cases and controls on the scans both before and at TEA. Absolute thalamic volumes were significantly reduced at TEA but not on the earlier scans. Data acquired in infancy showed lower FA values in infants with c-PVL. CONCLUSIONS: Damage to the CST can be identified on the early scan and persists, whereas the changes in thalamic volume develop in the weeks between the early and term equivalent magnetic resonance imaging. This may reflect the difference between acute and remote effects of the extensive injury to the white matter caused by c-PVL.

Evaluation of the genetic association of the PTPN22 R620W polymorphism in familial and sporadic systemic lupus erythematosus.

OBJECTIVE: The R620W (1858C-->T) polymorphism in PTPN22 has been implicated in type 1 diabetes mellitus, rheumatoid arthritis, Graves' disease, Hashimoto thyroiditis, autoimmune thyroid disease, and systemic lupus erythematosus (SLE). The aim of this study was to evaluate this polymorphism in patients with familial SLE and in those with sporadic SLE. METHODS: A total of 4,981 DNA samples were genotyped (from 1,680 SLE patients, 1,834 family members, and 1,467 controls). Both population-based case-control and family-based association designs were used for the analyses. RESULTS: In the European American familial SLE cohort, the minor 1858T allele was more common in randomly selected patients compared with controls (chi2= 5.61, P = 0.018, odds ratio [OR] 1.46, 95% confidence interval [95% CI] 1.07-1.99). The heterozygous C/T genotype was also more common in these European American patients compared with controls (OR 1.63, 95% CI 1.15-2.30). Family-based association tests showed preferential transmission of the 1858T allele to affected offspring (chi2 = 5.87, P = 0.015). In contrast, the frequency of the 1858T minor allele was not significantly increased in the European American patients with sporadic SLE compared with controls, nor did these patients have preferential transmission of the 1858T allele. Indeed, the difference in the 1858T allele frequency between patients with familial SLE and those with sporadic SLE was measurable (allelic chi2= 4.22, P = 0.04, OR 1.51, 95% CI 1.02-2.24). Our data also showed that among patients with SLE, the 1858T allele was separately associated with type 1 diabetes mellitus and with autoimmune thyroid disease, confirming the findings of other investigators. CONCLUSION: The 1858T allele of PTPN22 is associated with familial SLE but not with sporadic SLE in European Americans, thereby potentially explaining previous contradictory reports.