Predicting disability progression and cognitive worsening in multiple sclerosis using patterns of grey matter volumes

OBJECTIVE: In multiple sclerosis (MS), MRI measures at the whole brain or regional level are only modestly associated with disability, while network-based measures are emerging as promising prognostic markers. We sought to demonstrate whether data-driven patterns of covarying regional grey matter (GM) volumes predict future disability in secondary progressive MS (SPMS). METHODS: We used cross-sectional structural MRI, and baseline and longitudinal data of Expanded Disability Status Scale, Nine-Hole Peg Test (9HPT) and Symbol Digit Modalities Test (SDMT), from a clinical trial in 988 people with SPMS. We processed T1-weighted scans to obtain GM probability maps and applied spatial independent component analysis (ICA). We repeated ICA on 400 healthy controls. We used survival models to determine whether baseline patterns of covarying GM volume measures predict cognitive and motor worsening. RESULTS: We identified 15 patterns of regionally covarying GM features. Compared with whole brain GM, deep GM and lesion volumes, some ICA components correlated more closely with clinical outcomes. A mainly basal ganglia component had the highest correlations at baseline with the SDMT and was associated with cognitive worsening (HR=1.29, 95% CI 1.09 to 1.52, p<0.005). Two ICA components were associated with 9HPT worsening (HR=1.30, 95% CI 1.06 to 1.60, p<0.01 and HR=1.21, 95% CI 1.01 to 1.45, p<0.05). ICA measures could better predict SDMT and 9HPT worsening (C-index=0.69-0.71) compared with models including only whole and regional MRI measures (C-index=0.65-0.69, p value for all comparison <0.05). CONCLUSIONS: The disability progression was better predicted by some of the covarying GM regions patterns, than by single regional or whole-brain measures. ICA, which may represent structural brain networks, can be applied to clinical trials and may play a role in stratifying participants who have the most potential to show a treatment effect

Wells\u2019 syndrome in childhood: two case reports with review of the literature

Wells\u2019 syndrome, or eosinophilic cellulitis, is a rare disorder manifesting with acute erythematous and edematous plaques which resolve completely. Bullous lesions are uncommon, especially in childhood.We present two pediatric cases of bullous Wells\u2019 syndrome, one 3-year-old boy with atypical cutaneous manifestations and one 6-month-old girl with typical skin lesions. No trigger factors could be identified in both cases. Treatment with topical and systemic steroids was performed. Both patients had no recurrences after two years. Fortyfive pediatric cases of Wells\u2019 syndrome have been reported in the literature with an average age of onset of five years. In only seven cases bullous lesions were present. In about half of the patients a precipitating factor has been identified, including infections, arthropod bites, drug administration and hematologic disorder

Plasmacytoid dendritic cell leukemia: a rapidly evolving disease presenting with skin lesions sensitive to radiotherapy plus hyperthermia.

Plasmacytoid dendritic cell leukemia (pDCL) is a rapidly evolving disease, which frequently presents with skin lesions, particularly nodules and plaques with a typical reddish-brown or brown color. Treatment of pDCL is based on multiagent chemotherapy followed by allogeneic hematopoietic stem cell transplant, but skin lesions may be refractory to therapy. Here, we report on a 61-year-old patient affected by pDCL who first presented with multiple cutaneous nodules and plaques on the trunk. Lesions showed an excellent response to radiotherapy plus hyperthermia. Although this treatment did not avoid the systemic evolution of disease, it resolved skin lesions and prevented their relapse, thus representing a therapeutic option to be used in combination with chemotherapy regimens. The case presentation is followed by a general discussion with an emphasis on the diagnosis and treatment of this rare malignancy. The Oncologist 2009; 14: 1205-120