Inter-rater reliability of risk of bias tools for non-randomized studies.

PURPOSE: There is limited knowledge on the reliability of risk of bias (ROB) tools for assessing internal validity in systematic reviews of exposure and frequency studies. We aimed to identify and then compare the inter-rater reliability (IRR) of six commonly used tools for frequency (Loney scale, Gyorkos checklist, American Academy of Neurology [AAN] tool) and exposure (Newcastle-Ottawa scale, SIGN50 checklist, AAN tool) studies. METHODS: Six raters independently assessed the ROB of 30 frequency and 30 exposure studies using the three respective ROB tools. Articles were rated as low, intermediate, or high ROB. We calculated an intraclass correlation coefficient (ICC) for each tool and category of ROB tool. We compared the IRR between ROB tools and tool type by inspection of overlapping ICC 95% CIs and by comparing their coefficients after transformation to Fisher's Z values. We assessed the criterion validity of the AAN ROB tools by calculating an ICC for each rater in comparison with the original ratings from the AAN. RESULTS: All individual ROB tools had an IRR in the substantial range or higher (ICC point estimates between 0.61 and 0.80). The IRR was almost perfect (ICC point estimate > 0.80) for the AAN frequency tool and the SIGN50 checklist. All tools were comparable in IRR, except for the AAN frequency tool which had a significantly higher ICC than the Gyorkos checklist (p = 0.021) and trended towards a higher ICC when compared to the Loney scale (p = 0.085). When examined by category of ROB tool, scales, and checklists had a substantial IRR, whereas the AAN tools had an almost perfect IRR. For the criterion validity of the AAN ROB tools, the average agreement between our raters and the original AAN ratings was moderate. CONCLUSION: All tools had substantial IRRs except for the AAN frequency tool and the SIGN50 checklist, which both had an almost perfect IRR. The AAN ROB tools were the only category of ROB tools to demonstrate an almost perfect IRR. This category of ROB tools had fewer and simpler criteria. Overall, parsimonious tools with clear instructions, such as those from the AAN, may provide more reliable ROB assessments.

Progressive supranuclear palsy: current approach and challenges to diagnosis and treatment.

PURPOSE OF REVIEW: Since the original description of progressive supranuclear palsy (PSP) by Steele, Richardson and Olszewski, the clinical spectrum of PSP has expanded and now includes multiple phenotypic variants linked by a common disease. In this review, we discuss the evolution of the PSP syndrome and clinical criteria, with a particular focus on the 2017 Movement Disorders Society PSP criteria, its application and limitations. We also discuss our current approach to diagnosis and treatment. RECENT FINDINGS: There is a significant overlap between the different variants of PSP and multiple phenotypes that may be applied to the same patient simultaneously. Variant severity and predominance also evolve throughout the course of the disease. Each variant and level of certainty is associated with different specificity and sensitivity for underlying disease. The differential diagnosis of PSP is continuously evolving and includes other tauopathies, neurodegenerative, genetic, autoimmune and infectious disorders. MRI measurements can aid in the diagnosis. The first guidelines to help with clinical management of those patients have been recently published. SUMMARY: Although much improved, clinical PSP criteria alone remain insufficient and emphasize the need for improved biomarkers to identify patients at early stages to direct appropriate therapeutic strategies and target potential research.

Incidence and Prevalence of Drug-Resistant Epilepsy: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the incidence and prevalence of drug-resistant epilepsy (DRE) as well as its predictors and correlates, we conducted a systematic review and meta-analysis of observational studies. METHODS: Our protocol was registered with PROSPERO, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology reporting standards were followed. We searched MEDLINE, Embase, and Web of Science. We used a double arcsine transformation and random-effects models to perform our meta-analyses. We performed random-effects meta-regressions using study-level data. RESULTS: Our search strategy identified 10,794 abstracts. Of these, 103 articles met our eligibility criteria. There was high interstudy heterogeneity and risk of bias. The cumulative incidence of DRE was 25.0% (95% confidence interval [CI]: 16.8-34.3) in child studies but 14.6% (95% CI: 8.8-21.6) in adult/mixed age studies. The prevalence of DRE was 13.7% (95% CI: 9.2-19.0) in population/community-based populations but 36.3% (95% CI: 30.4-42.4) in clinic-based cohorts. Meta-regression confirmed that the prevalence of DRE was higher in clinic-based populations and in focal epilepsy. Multiple predictors and correlates of DRE were identified. The most reported of these were having a neurologic deficit, an abnormal EEG, and symptomatic epilepsy. The most reported genetic predictors of DRE were polymorphisms of the ABCB1 gene. CONCLUSIONS: Our observations provide a basis for estimating the incidence and prevalence of DRE, which vary between populations. We identified numerous putative DRE predictors and correlates. These findings are important to plan epilepsy services, including epilepsy surgery, a crucial treatment option for people with disabling seizures and DRE.

Similarities and Differences in the Pattern of Tau Hyperphosphorylation in Physiological and Pathological Conditions: Impacts on the Elaboration of Therapies to Prevent Tau Pathology.

Tau protein, a neuronal microtubule-associated protein, becomes hyperphosphorylated in several neurodegenerative diseases called tauopathies. Hyperphosphorylation of tau is correlated to its redistribution from the axon to the somato-dendritic compartment at early stages of tauopathies. Interestingly, tau hyperphosphorylation begins in different regions of the brain in each tauopathy. In some regions, both neurons and glial cells develop tau hyperphosphorylation. Tau hyperphosphorylation is also observed in physiological conditions such as hibernation and brain development. In the first section of present article, we will review the spatiotemporal and cellular distribution of hyperphosphorylated tau in the most frequent tauopathies. In the second section, we will compare the pattern of tau hyperphosphorylation in physiological and pathological conditions and discuss the sites that could play a pivotal role in the conversion of non-toxic to toxic forms of hyperphosphorylated tau. Furthermore, we will discuss the role of hyperphosphorylated tau in physiological and pathological conditions and the fact that tau hyperphosphorylation is reversible in physiological conditions but not in a pathological ones. In the third section, we will speculate how the differences and similarities between hyperphosphorylated tau in physiological and pathological conditions could impact the elaboration of therapies to prevent tau pathology. In the fourth section, the different therapeutic approaches using tau as a direct or indirect therapeutic target will be presented.