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Background and purpose Olfactory bulb atrophy is associated with cognitive dysfunction in Parkinson's and Alzheimer's disease, and with major depression. It has been suggested that olfactory bulb atrophy or dysfunction is therefore a marker of neurodegeneration. Multiple sclerosis ( MS) is now also recognized as having a significant neurodegenerative component. Thus, the aim of this study was to investigate associations between physical and cognitive disability, depression and olfactory bulb volume in MS. Methods In total, 146 patients with MS (mean age 49.0 ± 10.9 years, disease duration 21.2 ± 9.3 years, median Expanded Disability Status Scale ( EDSS) score 3.0 (range 0-7.5), 103 relapsing−remitting, 35 secondary progressive and eight primary progressive MS) underwent a standardized neurological examination, comprehensive neuropsychological testing and magnetic resonance imaging ( MRI); data of 27 healthy people served as age- and gender-matched control subjects. The olfactory bulb was semi-automatically segmented on high-resolution three-dimensional T1-weighted MRI. Results Mean olfactory bulb volume was lower in MS patients than healthy controls (183.9 ± 40.1 vs. 209.2 ± 59.3 μl; P = 0.018 adjusted to intracranial volume). Olfactory bulb volume was similar across clinical disease subtypes and did not correlate with cognitive performance, EDSS scores or total proton density/T2 white matter lesion volume. However, in progressive MS, the mean olfactory bulb volume correlated with depression scores (Spearman's rho = −0.38, P < 0.05) confirmed using a multivariate linear regression analysis including cognitive fatigue scores. This association was not observed in relapsing−remitting MS. Conclusion Olfactory bulb volume was lower in MS than in healthy controls. Olfactory bulb volume does not seem to mirror cognitive impairment in MS; however, it is associated with higher depression scores in progressive MS. [ABSTRACT FROM AUTHOR]

This article discusses a new method for diagnosing brain lymphoma using nanopore sequencing of cerebrospinal fluid (CSF). The study demonstrates the clinical application of this method in two cases of CNS lymphoma. The researchers adapted their fast-track unsupervised machine learning approach for cases with a differential diagnosis of lymphoma and other malignant brain tumors. The results showed that nanopore sequencing-derived methylation patterns can be used for next-day diagnosis and treatment initiation. This point-of-care protocol has the potential to significantly reduce neurological impairment through timely and non-invasive testing. [Extracted from the article]

Background and purpose: Multiple sclerosis (MS) has been associated with deficits in social cognition. However, little is known about which domains of social cognition are predominantly affected and what other factors are associated with it. The aim was (i) to characterize social cognition deficit in a group of MS outpatients and (ii) to relate impairment in social cognition to overall cognitive status, depression and fatigue. Methods: Thirty-five MS patients (mean disease duration 12.9 years, median Expanded Disability Status Scale (EDSS) 3 and 34 healthy controls (HCs) were examined using the German version of the Geneva Social Cognition Scale to measure different domains of social cognition. Standard neuropsychological testing was applied to all patients and to 20 HCs. Patient-reported outcomes included questionnaires for fatigue, depression, anxiety and executivebehavioural disturbances. Results: The mean social cognition raw score was lower in the MS patients compared to the HCs (86.5 ± 8.7 vs. 91.2 ± 5.9, P = 0.005; d = 0.6) and did not correlate with EDSS or disease duration. The difference was driven by facial affect recognition and the understanding of complex social situations (14% and 23% of patients respectively under the cut-off). The impairment in these two tasks did not correlate with general cognitive performance or depression but with fatigue. Conclusions: The impairment in our group was restricted to high order and affective social cognition tasks and independent of general cognitive performance, EDSS, disease duration and depression. Fatigue correlated with social cognition performance, which might be due to common underlying neuronal networks. [ABSTRACT FROM AUTHOR]

Aims: To elucidate the relationship between tobacco smoking and depression, and to estimate the impact of other substance dependencies. Design: Cross-sectional. Participants: A total of 1,849 men and women were interviewed face-to-face using a validated structured questionnaire. According to their tobacco smoking behavior, participants were grouped into never smokers, ex-smokers and current smokers. Measurements: Data were generated through the WHO/ISBRA study, an international multicenter study with a cross-sectional design. A standardized questionnaire was administered face-to-face by trained interviewers. Logistic regression analysis was used to predict depression. Results: There was a significant difference across the 3 smoking groups in the number of subjects who had major depression (DSM-IV) during their lifetime. The highest rate of depressives was found in current smokers (23.7%), the lowest rate in never smokers (6.2%), while the rate of those who had quit smoking (14.6%) was between both. In a logistic regression analysis, alcohol dependence (both current and during lifetime) as well as cocaine dependence were significant predictors of depression. However, the association between smoking and depression still remained statistically significant. Conclusions: This study adds support to the evidence that smoking is linked to depression. It also elucidates the importance of taking into account alcohol and cocaine dependence since they have a significant impact on the relationship between smoking and depression. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and purpose: To investigate the relation of age at disease onset and clinical outcomes across the lifespan from adolescence in patients with multiple sclerosis (MS) on disease‐modifying therapy (DMT). Methods: We analysed data from the Swiss Association for Joint Tasks of Health Insurers database containing data from 14 718 patients with MS. Patients were included in this analysis when they were on DMT for at least 1 year. The influence of age at disease onset on future relapses and disability worsening was explored using multivariable Cox proportional hazard regression models. Results: Data from 9705 patients with MS were analysed. Pediatric‐onset MS patients (n = 236) had higher relapse rates and marginally slower disability worsening rates compared with adult‐onset MS (n = 9469). The risk of relapses was highest in childhood and decreased continuously to about 35 years of age. It remained stable for about a decade and then again continuously decreased. In contrast, disability worsening hazards remained stable from childhood to about 32 years of age and then increased sharply around the age of 45 years. Conclusions: Age is an important factor independently affecting clinical outcomes in MS. This should be considered when designing clinical trials or choosing DMT. [ABSTRACT FROM AUTHOR]

Background and purpose N-acetyl aspartate ( NAA) assessed using proton magnetic resonance spectroscopy (1H MRS) has a high pathological specificity for axonal density. Retinal nerve fibre layer thickness ( RNFLT) measured by using optical coherence tomography is increasingly used as a surrogate marker of neurodegeneration in multiple sclerosis ( MS). Our aim was to investigate the relation between RNFLT and NAA/creatine in brain normal-appearing white matter ( NAWM), their dynamics over time and the association with clinical outcome measures in relapsing MS. T2 WM lesions served as control tissue. Methods Forty-three MS patients underwent standardized neurological examination including the Expanded Disability Status Scale ( EDSS), Multiple Sclerosis Functional Composite ( MSFC) score, optical coherence tomography and magnetic resonance imaging including 1H MRS at baseline and after 1 year. Results At baseline, NAA/creatine level was lower in T2 WM lesions than in NAWM (1.64 ± 0.16 vs. 1.88 ± 0.24, P < 0.001). Lowest levels were found in secondary progressive MS ( SPMS). Mean RNFLT was higher in clinically isolated syndrome than in the combined group of relapsing−remitting MS and SPMS (99.8 ± 12.3 μm vs. 92.4 ± 12.8 μm, P = 0.038). In all patients, mean RNFLT decreased by 1.4% during follow-up. At baseline, MSFC z-scores correlated with NAA/creatine levels both in NAWM ( r = 0.42; P = 0.008) and T2 WM lesions ( r = 0.52, P = 0.004). NAWM NAA/creatine variation correlated with the RNFLT change over 1 year ( ρ = 0.43, P = 0.046). Conclusions N-acetyl aspartate/creatine level reduction correlated with RNFLT thinning over 1 year in an EDSS stable MS cohort suggesting that these techniques might be sensitive to detect subclinical disease progression. [ABSTRACT FROM AUTHOR]

Background Neurofilaments are promising biomarkers in multiple sclerosis ( MS) and increased levels in cerebrospinal fluid ( CSF) indicate axonal damage or degeneration. In a previous study, neurofilament light chain ( Nf L) levels in CSF of relapsing remitting ( RR) patients with MS were normalized by natalizumab treatment. Aims of the study We compared the coherence between Nf L and neurofilament heavy chain ( Nf HSMI35) levels in longitudinal CSF samples in a subset of these patients. Methods In 30 patients with RRMS, CSF was obtained prior to and following 12 months of natalizumab treatment. Nf HSMI35 was measured by an electrochemiluminescence-based immunoassay. Nf L levels were determined previously by the Uman Diagnostics NF-light® assay. Results Nf HSMI35 decreased in 73.3% and Nf L in 90% of the patients following natalizumab treatment (32.4 vs 27.4 pg/ml, P = 0.002 and 820 vs 375 pg/ml, P < 0.0001). Patients experiencing a relapse showed higher Nf HSMI35 levels compared with patients in remission (47.7 vs 27.6 pg/ml, n = 8, P = 0.001). This difference was less obvious for Nf L (1055 vs 725 pg/ml, P = 0.256). In patients in remission, Nf L levels were lower following natalizumab treatment (830 vs 365 pg/ml, n = 20, P = 0.0002), whereas the same comparison failed significance for Nf HSMI35 (28.3 vs 26.9 pg/ml, P = 0.086). Conclusions We confirm previous findings, indicating reduced axonal damage under natalizumab treatment by measuring Nf HSMI35, using an assay with independent methodology. In comparison with Nf HSMI35, Nf L changes were more pronounced and the treatment effect also included patients in remission. Our results suggest that Nf L is superior over Nf HSMI35 as therapeutic biomarker and is a promising candidate to measure neuroaxonal damage in MS treatment trials. [ABSTRACT FROM AUTHOR]

Background: Prevalence rates of headache in multiple sclerosis (MS) patients varied widely in recent studies. This study aimed to investigate the 1 year prevalence of headache in MS compared with the general population. Methods: Population-based case–control study in Germany. Results: We included 491 patients with definite MS (68% female, mean age 45.3 years, 63.7% relapsing remitting MS, mean Expanded Disability Status Scale (EDSS) 3.2, 106 treated with interferon-β, 53 with glatiramer acetate, 271 untreated) and 447 age and gender matched controls. Headache was diagnosed with a validated questionnaire according to the International Headache Society Criteria. Headache prevalence was 56.2% (tension type headache 37.2%, migraine 24.6%). Headache prevalence rates did not differ from controls. Headache was not associated with disability or treatment. Trigeminal neuralgia was found in 6.3% of MS cases. Conclusion: Results suggest that headache in MS patients reflects comorbidity in most conditions. [ABSTRACT FROM AUTHOR]

Previously, we determined that training with vibrotactile feedback (VTfb) of trunk sway improves MS patients' balance impairment. Here, we posed 5 questions: 1) How many weeks of VTfb training are required to obtain the best short-term carry over effect (CoE) with VTfb? 2) How long does the CoE last once VTfb training terminates? 3) Is the benefit similar for stance and gait? 4) Is position or velocity based VTfb more effective in reducing trunk sway? 5) Do patients' subjective assessments of balance control improve? Balance control of 16 MS patients was measured with gyroscopes at the lower trunk. The gyroscopes drove directionally active VTfb in a head-band. Patients trained twice per week with VTfb for 4 weeks to determine when balance control with and without VTfb stopped improving. Thereafter, weekly assessments without VTfb over 4 weeks and at 6 months determined when CoEs ended. A 20% improvement in balance to normal levels occurred with VTfb. Short term CoEs improved from 15 to 20% (p ≤ 0.001). Medium term (1–4 weeks) CoEs were constant at 19% (p ≤ 0.001). At 6 months improvement was not significant, 9%. Most improvement was for lateral sway. Equal improvement occurred when angle position or velocity drove VTfb. Subjectively, balance improvements peaked after 3 weeks of training (32%, p ≤ 0.05). 3–4 weeks VTfb training yields clinically relevant sway reductions and subjective improvements for MS patients during stance and gait. The CoEs lasted at least 1 month. Velocity-based VTfb was equally effective as position-based VTfb. • Described the effects of vibrotactile feedback training (VTfbT) on MS patients' balance. • Gyroscopes drove directionally active VTfb in a head-band and measured trunk sway. • A 20% improvement in balance to normal levels occurred with VTfbT. • Medium term (1-4 weeks) carry-over effects post-VTfbT were constant at 19%. • 3-4 weeks of VTfbT yielded both trunk sway reductions and subjective improvements. [ABSTRACT FROM AUTHOR]