Severity of Depression Predicts Remission Rates Using Transcranial Magnetic Stimulation

Background: Multiple factors likely impact response and remission rates in the treatment of depression with repetitive transcranial magnetic stimulation (rTMS). Notably the role of symptom severity in outcomes with rTMS is poorly understood.Objective/Hypothesis: This study investigated the predictors of achieving remission in patients suffering from depression who receive ≥3 rTMS treatments per week. Methods: Available data on 41 patients treated at Walter Reed National Military Medical Center from 2009 to 2014 were included for analysis. Patients received a range of pulse sequences from 3,000 to 5,000 with left sided or bilateral coil placement. Primary outcome measures were total score on the Patient Health Questionnaire (PHQ-9) or the Quick Inventory of Depressive Symptomatology—Self Rated (QIDS-SR). Remission was defined as a total score less than five, and response was defined as a 50% decrease in the total score on both outcome metrics. Outcomes in patients diagnosed as suffering from mild or moderate depression were compared to those suffering from severe depression. Results: Of the 41 patients receiving treatment, 16 reached remission by the end of treatment. Remission rate was associated with the initial severity of depression, with patients with mild or moderate depression reaching remission at a significantly higher rate than those with severe depression. Total number of rTMS sessions or length of treatment were not predictors of remission. Conclusion: Patients with a baseline level of depression characterized as mild or moderate had significantly better outcomes following rTMS compared to patients with severe depression

Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker

School absenteeism in children with special health care needs : results from the prospective cohort study ikidS

Objective Children with special health care needs (SHCN) due to a chronic health condition perform more poorly at school compared to their classmates. There is still little knowledge on the causal pathways and which factors could be targeted by interventions. We, therefore, investigated school absenteeism in children with SHCN compared to their peers. Methods This study was based on data from the German population-based prospective cohort study ikidS (German for: I will start school). Children with SHCN were identified by the Children with Special Health Care Needs screener that captures five consequences of physical or mental chronic health conditions: (1) use or need of prescription medication, (2) above average use or need of medical, mental health, or educational services, (3) functional limitations compared with others of the same age, (4) use or need of specialized therapies, and (5) treatment or counseling for emotional, behavioral, or developmental problems. School absenteeism was defined as days absent from school due to illness during first grade and was reported by classroom teachers. Associations between SHCN consequences and school absenteeism were investigated by negative binomial regression models. Effect estimates were adjusted for confounding variables identified by a causal framework and directed acyclic graphs. Results 1,921 children (mean age at follow-up 7.3 years, standard deviation 0.3; 49% females) were included; of these, 14% had SHCN. Compared to their classmates, children with SHCN had more days absent (adjusted rate ratio: 1.37; 95% confidence interval 1.16, 1.62). The effect was strongest among children with i) functional limitations, ii) treatment or counseling for emotional, behavioral, or developmental problems, and iii) those who experienced two or more SHCN consequences. Conclusions Children with SHCN have higher school absenteeism, which could–at least partly–explain their poorer school performance and lower educational attainment. SHCN-specific targeted interventions may reduce the adverse effects of SHCN on educational outcomes in children

Konsensusprotokoll zur Standardisierung von Entnahme und Biobanking des Liquor cerebrospinalis

Die Erforschung von Biomarkern in Körperflüssigkeiten bei neurodegenerativen und neuroinflammatorischen Erkrankungen blickt auf eine langjährige Geschichte zurück. Dennoch werden nur wenige Liquor cerebrospinalis (Liquor)-Biomarker in der klinischen Praxis verwendet. Einer der problematischen Faktoren in der Liquorbiomarker-Forschung ist die eingeschränkte Aussagekraft von Studien aufgrund einer nicht ausreichend großer Anzahl von Proben, die in Studien von einzelnen Zentren akquiriert werden können. Deshalb ist die Kooperation zwischen mehreren Zentren erforderlich, um große Biobanken von definierten Proben zu etablieren. Standardisierte Protokolle für Biobanking sind unumgänglich, um die durch die größere Anzahl von Liquorproben gewonnene statistische Aussagekraft sicherzustellen und nicht durch mangelhafte Präanalytik einzuschränken. Hier wird ein Konsensusbericht über Leitlinien zu Liquorentnahme und Biobanking durch das BioMS-eu Netzwerk für Liquorbiomarker-Forschung in Multipler Sklerose präsentiert. Schwerpunkte des Berichts sind Liquorentnahme, präanalytische Faktoren und klinische sowie sonstige Informationen. Biobanking-Protokolle sind für Liquor-Biobanken im Rahmen der Erforschung jeder neurologischen Krankheit anwendba

Reduced Plasma Levels of 25-Hydroxycholesterol and Increased Cerebrospinal Fluid Levels of Bile Acid Precursors in Multiple Sclerosis Patients

Multiple sclerosis (MS) is an autoimmune, inflammatory disease of the central nervous system (CNS). We have measured the levels of over 20 non-esterified sterols in plasma and cerebrospinal fluid (CSF) from patients suffering from MS, inflammatory CNS disease, neurodegenerative disease and control patients. Analysis was performed following enzyme-assisted derivatisation by liquid chromatography-mass spectrometry (LC-MS) exploiting multistage fragmentation (MS n ). We found increased concentrations of bile acid precursors in CSF from each of the disease states and that patients with inflammatory CNS disease classified as suspected autoimmune disease or of unknown aetiology also showed elevated concentrations of 25-hydroxycholestertol (25-HC, P < 0.05) in CSF. Cholesterol concentrations in CSF were not changed except for patients diagnosed with amyotrophic lateral sclerosis (P < 0.01) or pathogen-based infections of the CNS (P < 0.05) where they were elevated. In plasma, we found that 25-HC (P < 0.01), (25R)26-hydroxycholesterol ((25R)26-HC, P < 0.05) and 7α-hydroxy-3-oxocholest-4-enoic acid (7αH,3O-CA, P < 0.05) were reduced in relapsing-remitting MS (RRMS) patients compared to controls. The pattern of reduced plasma levels of 25-HC, (25R)26-HC and 7αH,3O-CA was unique to RRMS. In summary, in plasma, we find that the concentration of 25-HC in RRMS patients is significantly lower than in controls. This is consistent with the hypothesis that a lower propensity of macrophages to synthesise 25-HC will result in reduced negative feedback by 25-HC on IL-1 family cytokine production and exacerbated MS. In CSF, we find that the dominating metabolites reflect the acidic pathway of bile acid biosynthesis and the elevated levels of these in CNS disease is likely to reflect cholesterol release as a result of demyelination or neuronal death. 25-HC is elevated in patients with inflammatory CNS disease probably as a consequence of up-regulation of the type 1 interferon-stimulated gene cholesterol 25-hydroxylase in macrophage

The Swiss Multiple Sclerosis Cohort-Study (SMSC): A Prospective Swiss Wide Investigation of Key Phases in Disease Evolution and New Treatment Options.

The mechanisms leading to disability and the long-term efficacy and safety of disease modifying drugs (DMDs) in multiple sclerosis (MS) are unclear. We aimed at building a prospective cohort of MS patients with standardized collection of demographic, clinical, MRI data and body fluids that can be used to develop prognostic indicators and biomarkers of disease evolution and therapeutic response. The Swiss MS Cohort (SMSC) is a prospective observational study performed across seven Swiss MS centers including patients with MS, clinically isolated syndrome (CIS), radiologically isolated syndrome or neuromyelitis optica. Neurological and radiological assessments and biological samples are collected every 6-12 months. We recruited 872 patients (clinically isolated syndrome [CIS] 5.5%, relapsing-remitting MS [RRMS] 85.8%, primary progressive MS [PPMS] 3.5%, secondary progressive MS [SPMS] 5.2%) between June 2012 and July 2015. We performed 2,286 visits (median follow-up 398 days) and collected 2,274 serum, plasma and blood samples, 152 cerebrospinal fluid samples and 1,276 brain MRI scans. 158 relapses occurred and expanded disability status scale (EDSS) scores increased in PPMS, SPMS and RRMS patients experiencing relapses. Most RRMS patients were treated with fingolimod (33.4%), natalizumab (24.5%) or injectable DMDs (13.6%). The SMSC will provide relevant information regarding DMDs efficacy and safety and will serve as a comprehensive infrastructure available for nested research projects

Consensus guidelines for lumbar puncture in patients with neurological diseases

Introduction Cerebrospinal fluid collection by lumbar puncture (LP) is performed in the diagnostic workup of several neurological brain diseases. Reluctance to perform the procedure is among others due to a lack of standards and guidelines to minimize the risk of complications, such as post-LP headache or back pain. Methods We provide consensus guidelines for the LP procedure to minimize the risk of complications. The recommendations are based on (1) data from a large multicenter LP feasibility study (evidence level II-2), (2) systematic literature review on LP needle characteristics and post-LP complications (evidence level II-2), (3) discussion of best practice within the Joint Programme Neurodegenerative Disease Research Biomarkers for Alzheimer's disease and Parkinson's Disease and Biomarkers for Multiple Sclerosis consortia (evidence level III). Results Our consensus guidelines address contraindications, as well as patient-related and procedure-related risk factors that can influence the development of post-LP complications. Discussion When an LP is performed correctly, the procedure is well tolerated and accepted with a low complication rate

In vivo PET imaging of the neuroinflammatory response in rat spinal cord injury using the TSPO tracer [F-18]GE-180 and effect of docosahexaenoic acid

Centre for Trauma Sciences, funded by the Barts & The London Charity, GE Healthcare Ltd, the Experimental Medicine Awards from the Blizard Institute and the Imaging Centre at the Barts Cancer Institute

Testing the predictability and efficiency of securitized real estate markets

This paper conducts tests of the random walk hypothesis and market efficiency for 14 national public real estate markets. Random walk properties of equity prices influence the return dynamics and determine the trading strategies of investors. To examine the stochastic properties of local real estate index returns and to test the hypothesis that public real estate stock prices follow a random walk, the single variance ratio tests of Lo and MacKinlay (1988) as well as the multiple variance ratio test of Chow and Denning (1993) are employed. Weak-form market efficiency is tested directly using non-parametric runs tests. Empirical evidence shows that weekly stock prices in major securitized real estate markets do not follow a random walk. The empirical findings of return predictability suggest that investors might be able to develop trading strategies allowing them to earn excess returns compared to a buy-and-hold strategy