Multiple sclerosis (MS) is a complex disease that seems to depend on several pathophysiological processes. Because of its varied clinical presentation, natural history, and response to therapeutic interventions, MS can be considered to be a group of diseases that have not been yet characterized, thus resulting in difficult evaluation of prognosis. In the last few years, the role of autoAbs in MS has been reevaluated, and, therefore, their identification as specific biomarkers became a relevant target. In this paper, we demonstrate that an aberrant N-glucosylation is a fundamental determinant of autoAb recognition in MS. Thus, we developed CSF114(Glc), an antigenic probe accurately measuring IgM autoAbs in the sera of a patient population, as disease biomarker. The relevance of CSF114(Glc) is demonstrated by its clinical application and correlation with disease activity and prognosis. In fact, CSF114(Glc), a structure-based designed glycopeptide, is able to recognize, by ELISA, the presence of specific IgM autoAbs in the sera of a MS patient population but not in blood donors and other autoimmune conditions. AutoAbs specific for CSF114(Glc) isolated from MS patients recognized myelin and oligodendrocyte antigens by immunohistochemistry but not other nonrelevant tissues. We demonstrate that CSF114(Glc) is a reliable, specific probe in a longitudinal study of untreated MS patients. Development of IgG/IgM anti-CSF114(Glc) Abs paralleled clinical activity and brain lesions positive to MRI. Therefore, a CSF114(Glc)-based immunoassay on sera may have important prognostic value in monitoring MS disease progression guiding optimal therapeutic treatment.

Magnetic resonance (MR) techniques enable in vivo measurement of the atrophy of the brainstem and cerebellum in spinocerebellar ataxia type 1 (SCA1) and 2 (SCA2) patients, which is accompanied by a decrease in the concentration of N-acetyl aspartate (NAA) or of the NAA/creatine ratio in the pons and cerebellum. Mean diffusivity (D̅) is emerging as an additional sensitive and quantitative MR parameter to investigate brain diseases. In order to explore differences between the MR features of SCA1 and SCA2 and correlate the MR and clinical findings in the two conditions, we examined 16 SCA1 patients, 12 SCA2 patients and 20 healthy control subjects. The MR protocol included T1-weighted 3D gradient echo sequences, single-voxel proton spectroscopy of the right cerebellar hemisphere (dentate and peridentate region) and of the pons with a PRESS sequence and an external reference quantitation method, and (in nine patients with SCA1 and nine patients with SCA2) diffusion-weighted echo-planar images with reconstruction of the D̅ maps. The patients were evaluated with the Inherited Ataxia Clinical Rating Scale (IACRS). Compared with control subjects, the SCA1 and SCA2 patients showed a decrease (P < 0.01) in the volume of the brainstem and cerebellum and in the concentration of NAA in the pons and cerebellar hemisphere, whereas D̅ of the brainstem and cerebellum was increased. No significant difference was observed between the SCA1 and SCA2 patient groups. No correlation between cerebellar volume and dentate and peridentate NAA concentration was found in SCA1 or SCA2 patients. The volume of the brainstem, D̅ of the brainstem and cerebellum and the concentration of NAA in the pons were correlated (P < 0.05) with the IACRS score in SCA1 but not in SCA2. This discrepancy is in line with the clinical observation that the clinical deficit has a later onset and faster progression in SCA1 and an earlier onset and slower progression in SCA2, and suggests that neurodegeneration of the brainstem is a comparatively more rapid process in SCA1. In conclusion, our study indicates that SCA1 and SCA2 substantially exhibit the same MR features. The correlation in SCA1 between clinical severity and quantitative volumetric, diffusion MRI and proton MR spectroscopy findings in the brainstem indicates that these measurements might be employed for longitudinal studies and hopefully as surrogate markers in future pharmacological trials of this condition.

To investigate whether diffusion-weighted and magnetization transfer (MT) magnetic resonance (MR) imaging depict regional and/or global brain abnormalities in patients with Huntington disease (HD). Twenty-one carriers of the HD mutation (mean age, 58 years +/- 11 [SD]) and 21 healthy control subjects (mean age, 54 years +/- 13) underwent conventional, diffusion-weighted, and MT MR imaging. Volumes, mean apparent diffusion coefficients (ADCs), and MT ratios (MTRs) for left and right caudate nucleus, putamen, and cerebral periventricular white matter-as well as an index of normalized brain volume and whole-brain ADC and MT histograms-were computed. Asymmetry in volume, ADC, and MTR measurements in caudate nucleus, putamen, and periventricular white matter in control subjects and HD carriers were evaluated with Wilcoxon testing for paired samples. Differences in MR imaging variables between HD carriers and control subjects were evaluated with Mann-Whitney U testing; correlations between stages of clinical severity and MR imaging data were investigated with Spearman rank correlation testing. No significant asymmetry was observed for any of the MR imaging variables. Caudate nucleus, putamen, and whole-brain volumes were smaller (P <.001 for all) in HD carriers than in control subjects. HD carriers also had increased ADC in the caudate nucleus (P =.002), putamen (P <. 001), cerebral periventricular white matter (P <.001), and whole brain (P <.001). MTR was not significantly different between HD carriers and control subjects. Correlation was observed between stages of increasing clinical disease severity and both decrease in volume of caudate nucleus (Spearman rho = -0.63), putamen (rho = -0.64), and whole brain (rho = -0.46) and increase in ADC in caudate nucleus (rho = 0.52), periventricular white matter (rho = 0.45), and whole brain (rho = 0.44). Regional and global volume loss in HD is accompanied by an increase in ADC; this correlates with disease severity.