i(3)so3-galactosylceramide and Movement-Disorders

Metachromatic leukodystrophy (MLD) is a rare metabolic disorder leading to demyelination and rapid neurologic deterioration. As therapeutic options evolve, it seems essential to understand and quantify progression of the natural disease. The aim of this study was to assess cerebral volumetric changes in children with MLD in comparison to normal controls and in relation to disease course.. Eighteen patients with late-infantile MLD and 42 typically developing children in the same age range (20-59 months) were analyzed in a cross-sectional study. Patients underwent detailed genetic, biochemical, electrophysiologic, and clinical characterization. Cerebral gray matter (GM) and white matter (WM) volumes were assessed by multispectral segmentation of T1- and T2-weighted MRI. In addition, the demyelinated WM (demyelination load) was automatically quantified in T2-weighted images of the patients, and analyzed in relation to the clinical course.. WM volumes of patients did not differ from controls, although their growth curves were slightly different. GM volumes of patients, however, were on average 10.7% (confidence interval 6.0%-14.9%, p < 0.001) below those of normally developing children. The demyelination load (corrected for total WM volume) increased with disease duration (p < 0.003) and motor deterioration (p < 0.001).. GM volume in patients with MLD is reduced when compared with healthy controls, already at young age. This supports the notion that, beside demyelination, neuronal dysfunction caused by neuronal storage plays an additional role in the disease process. The demyelination load may be a useful noninvasive imaging marker for disease progression and may serve as reference for therapeutic intervention.

Topics: Adolescent; Adult; Aging; Cerebral Cortex; Child; Confidence Intervals; Cross-Sectional Studies; Demyelinating Diseases; Disease Progression; Female; Humans; Image Processing, Computer-Assisted; Leukodystrophy, Metachromatic; Magnetic Resonance Imaging; Male; Middle Aged; Movement Disorders; Myelin Sheath; Neural Conduction; Regression Analysis; Sulfoglycosphingolipids; Young Adult

Phospholipids are abundantly represented within the nervous system. Aim of our study was to evaluate the presence and fine specificity of anti phospholipid antibodies (aPLAb) among patients with monoclonal gammopathy associated neuropathy. Thirty nine percent of these patients had high titers of aPLAb, mostly associated with low levels of anti beta2 glycoprotein I, which suggests different antibody specificity compared to patients with anti phospholipid syndrome. Further 6/48 patients with dysimmune neuropathy without monoclonal gammopathy had positive aPLAb titers. APLAb strongly cross-reacted with sulfatide. These findings suggest an adjuntive role of aPLAb on nerve damage and may help to better understand the nerve binding properties of anti-sulfatide antibodies.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Antiphospholipid; Antibody Specificity; Autoantibodies; beta 2-Glycoprotein I; Cross Reactions; Female; Humans; Male; Middle Aged; Movement Disorders; Nervous System Diseases; Paraproteinemias; Polyneuropathies; Prospective Studies; Sensation Disorders; Sulfoglycosphingolipids

Topics: Animals; Brain; Brain Stem; Carbon Radioisotopes; Central Nervous System; Ceramides; Cerebellum; Cerebrosides; Cholesterol; Chromatography, Thin Layer; Copper; Deficiency Diseases; Disease Models, Animal; Female; Galactose; Gangliosides; Hexosyltransferases; Male; Movement Disorders; Myelin Sheath; Phosphatidylcholines; Phosphatidylethanolamines; Rats; Sphingomyelins; Sulfoglycosphingolipids