Neuropsychiatric symptoms and reduced health-related quality of life (HRQoL) are frequent in multiple sclerosis, where are associated with structural brain changes, but have been less studied in clinically isolated syndrome (CIS).To characterize HRQoL, neuropsychiatric symptoms (depressive symptoms, anxiety, apathy and fatigue), their interrelations and associations with structural brain changes in CIS.Patients with CIS (n = 67) and demographically matched healthy controls (n = 46) underwent neurological and psychological examinations including assessment of HRQoL, neuropsychiatric symptoms and cognitive functioning, and MRI brain scan with global, regional and lesion load volume measurement.The CIS group had more, mostly mild, depressive symptoms and anxiety, and lower HRQoL physical and social subscores (p≤0.037). Neuropsychiatric symptoms were associated with most HRQoL subscores (β≤-0.34, p≤0.005). Cognitive functioning unlike clinical disability was associated with depressive symptoms and lower HRQoL emotional subscores (β≤-0.29, p≤0.019). Depressive symptoms and apathy were associated with right temporal, left insular and right occipital lesion load (ß≥0.29, p≤0.032). Anxiety was associated with lower white matter volume (ß = -0.25, p = 0.045).Mild depressive symptoms and anxiety with decreased HRQoL are present in patients with CIS. Neuropsychiatric symptoms contributing to decreased HRQoL are the result of structural brain changes and require complex therapeutic approach in patients with CIS.
Interferon-β (IFNß) is the first-line treatment for relapsing-remitting multiple sclerosis. Myxovirus resistance protein A (MxA) is a marker of IFNß bioactivity, which may be reduced by neutralizing antibodies (NAbs) against IFNß. The aim of the study was to analyze the kinetics of MxA mRNA expression during long-term IFNβ treatment and assess its predictive value.A prospective, observational, open-label, non-randomized study was designed in multiple sclerosis patients starting IFNß treatment. MxA mRNA was assessed prior to initiation of IFNß therapy and every three months subsequently. NAbs were assessed every six months. Assessment of relapses was scheduled every three months during 24 months of follow up. The disease activity was correlated to the pretreatment baseline MxA mRNA value. In NAb negative patients, clinical status was correlated to MxA mRNA values.119 patients were consecutively enrolled and 107 were included in the final analysis. There was no correlation of MxA mRNA expression levels between baseline and month three. Using survival analysis, none of the selected baseline MxA mRNA cut off points allowed prediction of time to first relapse on the treatment. In NAb negative patients, mean MxA mRNA levels did not significantly differ in patients irrespective of relapse status.Baseline MxA mRNA does not predict the response to IFNß treatment or the clinical status of the disease and the level of MxA mRNA does not correlate with disease activity in NAb negative patients.
Vertigo/dizziness or balance disorders are among the most common patients complaints in emergency clinics. Up to 25% of them are potentially life-threatening, especially cardiovascular or cerebrovascular events. The combination of a careful history taking (triggers, duration of difficulties, associated symptoms) and the performance of a basic vestibular examination (nystagmus, oculomotor, head impulse test, positional maneuvers, standing and walking examination) leads to a reliable differentiation of central and peripheral vestibular etiology. Standardized diagnostic algorithms (HINTS, HINTS+, STANDING) are used to identify high-risk patients requiring urgent care. Imaging methods must be interpreted with caution to their low sensitivity in acute phase (sensitivity of non-contrast brain CT for ischemia in the posterior cranial fossa is only 16%, MRI of the brain is false negative in up to 20% of cases in stroke patients in the first 48 hours).
Spatial navigation impairment is a promising cognitive marker of Alzheimer's disease (AD) that can reflect the underlying pathology.We assessed spatial navigation performance in AD biomarker positive older adults with amnestic mild cognitive impairment (AD aMCI) vs. those AD biomarker negative (non-AD aMCI), and examined associations between navigation performance, MRI measures of brain atrophy, and cerebrospinal fluid (CSF) biomarkers.A total of 122 participants with AD aMCI (n = 33), non-AD aMCI (n = 31), mild AD dementia (n = 28), and 30 cognitively normal older adults (CN) underwent cognitive assessment, brain MRI (n = 100 had high-quality images for volumetric analysis) and three virtual navigation tasks focused on route learning (body-centered navigation), wayfinding (world-centered navigation) and perspective taking/wayfinding. Cognitively impaired participants underwent CSF biomarker assessment [amyloid-β1-42, total tau, and phosphorylated tau181 (p-tau181)] and amyloid PET imaging (n = 47 and n = 45, respectively), with a subset having both (n = 19).In route learning, AD aMCI performed worse than non-AD aMCI (p < 0.001), who performed similarly to CN. In wayfinding, aMCI participants performed worse than CN (both p ≤ 0.009) and AD aMCI performed worse than non-AD aMCI in the second task session (p = 0.032). In perspective taking/wayfinding, aMCI participants performed worse than CN (both p ≤ 0.001). AD aMCI and non-AD aMCI did not differ in conventional cognitive tests. Route learning was associated with parietal thickness and amyloid-β1-42, wayfinding was associated with posterior medial temporal lobe (MTL) volume and p-tau181 and perspective taking/wayfinding was correlated with MRI measures of several brain regions and all CSF biomarkers.AD biomarker positive and negative older adults with aMCI had different profiles of spatial navigation deficits that were associated with posterior MTL and parietal atrophy and reflected AD pathology.
Alzheimer's disease (AD) and Normal Pressure Hydrocephalus (NPH) are both associated with the cognitive decline and brain structural changes. To the best of our knowledge, there are no studies to date, comparing general patterns of white matter (WM) degeneration between AD and NPH patients with the use of Tract-Based Spatial Statistics (TBSS). The current study aims to conduct comparative evaluation of global WM alterations in both AD and NPH. We enrolled 17 patients with NPH, 14 with AD, and 17 healthy controls. Diffusion data were obtained and DTI metrics (FA, MD, L1) were evaluated by using TBSS analysis and compared among groups. WM microstructure as evaluated by group level voxel-wise FA differences in the centre of white matter fibre bundles was significantly altered in NPH patients as compared to controls. In NPH patients reduced FA was found over the corpus callosum, particularly in the splenium and additionally in the occipital (putative optic radiation) and parietal white matter. Contrary, FA was higher in NPH in the cortico-fugal fibres arising from the frontal and parietal cortex passing through the posterior limb of the internal capsule. Comparison between AD and NPH group showed higher FA values in AD group in the left occipital lobe (putative optic radiation). Contrary, FA was higher in NPH patients in the bilateral corona radiata, internal capsule on the left side and also bilaterally in the white matter anterior of the frontal horns of the lateral ventricles. While axial diffusivity (L1) was higher in NPH patients than in AD patients in the bilateral corticofugal fibres in the frontal and parietal white matter, perpendicular diffusivity was higher in the right parietal and frontal white matter adjacent to the anterior and posterior horn of the lateral ventricle and in the right thalamus. The results showed significant differences in patterns of WM alterations, not only between patients and healthy controls, but more interestingly also between NPH and AD patients. Our study demonstrated TBSS analysis as a useful approach in differentiating between AD and NPH, sensitive on the mictrostructural level, which may be useful in further evaluation of pathological conditions underlying primary and secondary MW alterations. White matter (WM) alterations in NPH compared to controls. Results are overlaid on the mean FA skeleton thresholded at 0.2. Significant clusters were thickened for better visualisation. Upper row: Higher FA in NPH patients comparing with controls are shown in green, and lower FA in blue. Second and third rows: Higher MD and axial diffusivity respectively in the NPH group are shown in red and lower FA values in purple. White matter (WM) alterations in NPH compared to AD patient. Results are overlaid on the mean FA skeleton thresholded at 0.2. Significant clusters were thickened for better visualisation. Green thickened clusters show higher parameters in NPH patients than in AD patients.
