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Cerebrospinal fluid (CSF) proteins may provide important information about the pathomechanisms present in multiple sclerosis (MS). Although diagnostic criteria for early MS are available, there is still a need for biomarkers, predicting disease subtype and progression to improve individually tailored treatment. Using the two-dimensional difference gel electrophoresis (2-D-DIGE) technology for comparative analysis, we compared CSF samples from patients with MS of the relapse-remitting type (RRMS, n = 12) and from patients with clinically isolated syndrome (CIS, n = 12) suggestive of a first demyelinating attack with neurologically normal controls. Protein spots that showed more than two-fold difference between patients and controls were selected for further analysis with MALDI-TOF mass spectrometry. Immunoblot analysis was performed to confirm the validity of individual candidate proteins. In RRMS, we identified 1 up-regulated and 10 down-regulated proteins. In CIS, 2 up-regulated and 11 down-regulated proteins were identified. One of these proteins (Apolipoprotein A1) was confirmed by immunoblot. Though the pathophysiological role of these proteins still remains to be elucidated in detail and further validation is needed, these findings may have a relevant impact on the identification of disease-specific markers. [ABSTRACT FROM AUTHOR]

Background.Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's ‘resting state’ could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients.Method.Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and ‘biological parametric mapping’ analyses to investigate the impact of atrophy on neural activity.Results.Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition.Conclusions.This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities. [ABSTRACT FROM AUTHOR]

BackgroundDepressive symptoms are prominent psychopathological features of Huntington's disease (HD), making a negative impact on social functioning and well-being.MethodWe compared the frequencies of a history of depression, previous suicide attempts and current subthreshold depression between 61 early-stage HD participants and 40 matched controls. The HD group was then split based on the overall HD group's median Hospital Anxiety and Depression Scale-depression score into a group of 30 non-depressed participants (mean 0.8, s.d. = 0.7) and a group of 31 participants with subthreshold depressive symptoms (mean 7.3, s.d. = 3.5) to explore the neuroanatomy underlying subthreshold depressive symptoms in HD using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI).ResultsFrequencies of history of depression, previous suicide attempts or current subthreshold depressive symptoms were higher in HD than in controls. The severity of current depressive symptoms was also higher in HD, but not associated with the severity of HD motor signs or disease burden. Compared with the non-depressed HD group DTI revealed lower fractional anisotropy (FA) values in the frontal cortex, anterior cingulate cortex, insula and cerebellum of the HD group with subthreshold depressive symptoms. In contrast, VBM measures were similar in both HD groups. A history of depression, the severity of HD motor signs or disease burden did not correlate with FA values of these regions.ConclusionsCurrent subthreshold depressive symptoms in early HD are associated with microstructural changes – without concomitant brain volume loss – in brain regions known to be involved in major depressive disorder, but not those typically associated with HD pathology. [ABSTRACT FROM AUTHOR]

Axonal damage has been proposed as the major substrate of permanent clinical disability in multiple sclerosis. Tau protein, a microtubule-associated protein localised in neuronal axons, may serve as a biochemical surrogate marker to evaluate axonal damage in vivo. We intended to determine the extent of axonal damage in different stages and clinical subtypes of MS by investigating cerebrospinal fluid tau concentrations. Tau was measured using an immunoassay in 35 patients with relapsing–remitting MS, eight patients with secondary progressive MS, nine patients with primary progressive MS, 50 patients with clinically isolated syndrome suggestive of early MS and 46 normal controls. Cerebrospinal fluid tau was significantly elevated in MS compared with normal controls (median 206.0 pg/mL versus 152.0 pg/mL; P = 0.002). No significant difference among different subtypes of MS could be detected, although highest levels were found in very early disease stages. There was a significant elevation of CSF tau among patients with gadolinium-enhancing brain lesions in magnetic resonance imaging (P = 0.02) and a tendency towards higher CSF tau levels in patients with pronounced intrathecal IgG synthesis, supporting the notion that axonal damage is influenced by inflammatory activity. [ABSTRACT FROM AUTHOR]