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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]

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]

Cerebrospinal fluid (CSF) analysis is of utmost importance to establish an early diagnosis of central nervous system (CNS) infections and to start appropriate therapy. The CSF white cell count, lactate concentration and total protein levels are usually available very quickly even from non-specialized laboratories and the combination of these parameters often provides sufficient information for decision-making in emergency cases. It is, however, not always possible to identify the underlying infective agent despite further CSF analyses, such as bacterial and fungal staining, evaluation of the blood-CSF barrier function, intrathecal immunoglobulin synthesis and oligoclonal IgG bands. Therefore, close communication between the laboratory and the clinician is an important prerequisite to specify additional pathogen-related diagnostic measures for successful confirmation of the diagnosis.

We used two-dimensional difference in-gel electrophoresis (2-D-DIGE) for proteome analysis of cerebrospinal fluid (CSF) in Guillain-Barré syndrome (GBS). Spots showing >2-fold difference between GBS and controls were analysed using MALDI-TOF mass spectrometry. Proteins that were up-regulated in GBS included haptoglobin, serine/threonine kinase 10, alpha-1-antitrypsin, SNC73, alpha II spectrin, IgG kappa chain and cathepsin D preprotein, while transferrin, caldesmon, GALT, human heat shock protein 70, amyloidosis patient HL-heart-peptide 127aa and transthyretin were down-regulated. Some of these proteins are reported in CSF of GBS for the first time. Accordingly, the 2-D-DIGE technology may be useful to identify disease-specific proteins in patients with GBS.

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.

Oxidative stress is involved in the aetiopathogenesis of amyotrophic lateral sclerosis (ALS), a fatal degenerative disorder. To test whether oxidative stress in ALS is increased and confined to the central nervous system, we have measured the glycoxidation product N(epsilon)-(carboxymethyl)lysine (CML) in serum and cerebrospinal fluid (CSF) samples by means of a novel enzyme immunoassay. Significant increases of CSF/serum ratio of CML in ALS patients (n = 25) as compared to normal controls (n = 20, p = 0.001) and to Alzheimer disease patients (n = 9, p = 0.029) suggest intrathecal production of this glycoxidation product. Measurement of CML levels may provide a novel diagnostic tool and may supplement current monitoring strategies in interventional trials.

Tau protein (tau) is primarily localised in neurons, and after brain parenchymal damage its release into cerebrospinal fluid (CSF) is increased. The particular influences of blood-CSF barrier function and of disease topography on CSF tau levels have not been studied yet. CSF tau concentrations determined by enzyme-immunoassay in various neurological diseases (n = 61) were not dependent upon blood-CSF barrier dysfunction. Significant elevation of tau levels in patients with meningoencephalitis and cerebral hemorrhage indicates brain parenchymal damage. In contrast, tau levels remained normal in patients with bacterial meningitis if encephalitic complications did not occur. In patients with Guillain-Barré syndrome tau levels were low. Increased tau levels in active multiple sclerosis compared to clinically nonactive states indicate axonal pathology in active disease.