87 research outputs found
An Acute Evolving Flaccid Quadriparesis in an Elderly Woman
Andrew Larner and colleagues discuss the differential diagnosis, investigation, and management of a 72-year-old woman presenting with progressive lower limb weakness who develops an acute evolving flaccid quadriparesis
A 50-Year-Old Man with Deteriorating Cognitive Function and Impaired Movement
Andrew Larner discusses the diagnosis and management of a man referred to the Cognitive Function Clinic with a 12- to 18-month history of deteriorating memory
Asterixis.
Adams and Foley described asterixis in the 1940s in patients with hepatic encephalopathy, but it has since been associated with a wide range of potential causes, both in neurology and general medicine. Here, we review the history, characteristics and clinical significance of this important clinical sign
Critical success index or F measure to validate the accuracy of administrative healthcare data identifying epilepsy in deceased adults in Scotland
Background: Methods to undertake diagnostic accuracy studies of administrative epilepsy data are challenged bylack of a way to reliably rank case-ascertainment algorithms in order of their accuracy. This is because it isdifficult to know how to prioritise positive predictive value (PPV) and sensitivity (Sens). Large numbers of truenegative (TN) instances frequently found in epilepsy studies make it difficult to discriminate algorithm accuracyon the basis of negative predictive value (NPV) and specificity (Spec) as these become inflated (usually >90%).This study demonstrates the complementary value of using weather forecasting or machine learning metricscritical success index (CSI) or F measure, respectively, as unitary metrics combining PPV and sensitivity. Wereanalyse data published in a diagnostic accuracy study of administrative epilepsy mortality data in Scotland.Method: CSI was calculated as 1/[(1/PPV) + (1/Sens) – 1]. F measure was calculated as 2.PPV.Sens/(PPV +Sens). CSI and F values range from 0 to 1, interpreted as 0 = inaccurate prediction and 1 = perfect accuracy. Thepublished algorithms were reanalysed using these and their accuracy re-ranked according to CSI in order to allowcomparison to the original rankings.Results: CSI scores were conservative (range 0.02–0.826), always less than or equal to the lower of the correspondingPPV (range 39–100%) and sensitivity (range 2–93%). F values were less conservative (range0.039–0.905), sometimes higher than either PPV or sensitivity, but were always higher than CSI. Low CSI and Fvalues occurred when there was a large difference between PPV and sensitivity, e.g. CSI was 0.02 and F was0.039 in an instance when PPV was 100% and sensitivity was 2%. Algorithms with both high PPV and sensitivityperformed best in terms of CSI and F measure, e.g. CSI was 0.826 and F was 0.905 in an instance when PPV was90% and sensitivity was 91%.Conclusion: CSI or F measure can combine PPV and sensitivity values into a convenient single metric that is easierto interpret and rank in terms of diagnostic accuracy than trying to rank diagnostic accuracy according to the twomeasures themselves. CSI or F prioritise instances where both PPV and sensitivity are high over instances wherethere are large differences between PPV and sensitivity (even if one of these is very high), allowing diagnosticaccuracy thresholds based on combined PPV and sensitivity to be determined. Therefore, CSI or F measures maybe helpful complementary metrics to report alongside PPV and sensitivity in diagnostic accuracy studies ofadministrative epilepsy data
Using Critical Success Index or Gilbert Skill score as composite measures of positive predictive value and sensitivity in diagnostic accuracy studies: weather forecasting informing epilepsy research
Accuracy of the short-form Montreal Cognitive Assessment: systematic review and validation
Introduction:
Short‐form versions of the Montreal Cognitive Assessment (SF‐MoCA) are increasingly used to screen for dementia in research and practice. We sought to collate evidence on the accuracy of SF‐MoCAs and to externally validate these assessment tools.
Methods:
We performed systematic literature searching across multidisciplinary electronic literature databases, collating information on the content and accuracy of all published SF‐MoCAs. We then validated all the SF‐MoCAs against clinical diagnosis using independent stroke (n = 787) and memory clinic (n = 410) data sets.
Results:
We identified 13 different SF‐MoCAs (21 studies, n = 6477 participants) with differing test content and properties. There was a pattern of high sensitivity across the range of SF‐MoCA tests. In the published literature, for detection of post stroke cognitive impairment, median sensitivity across included studies: 0.88 (range: 0.70‐1.00); specificity: 0.70 (0.39‐0.92). In our independent validation using stroke data, median sensitivity: 0.99 (0.80‐1.00); specificity: 0.40 (0.14‐0.87). To detect dementia in older adults, median sensitivity: 0.88 (0.62‐0.98); median specificity: 0.87 (0.07‐0.98) in the literature and median sensitivity: 0.96 (range: 0.72‐1.00); median specificity: 0.36 (0.14‐0.86) in our validation. Horton's SF‐MoCA (delayed recall, serial subtraction, and orientation) had the most favorable properties in stroke (sensitivity: 0.90, specificity: 0.87, positive predictive value [PPV]: 0.55, and negative predictive value [NPV]: 0.93), whereas Cecato's “MoCA reduced” (clock draw, animal naming, delayed recall, and orientation) performed better in the memory clinic (sensitivity: 0.72, specificity: 0.86, PPV: 0.55, and NPV: 0.93).
Conclusions:
There are many published SF‐MoCAs. Clinicians and researchers using a SF‐MoCA should be explicit about the content. For all SF‐MoCA, sensitivity is high and similar to the full scale suggesting potential utility as an initial cognitive screening tool. However, choice of SF‐MoCA should be informed by the clinical population to be studied
The Signal Transducer and Activator of Transcription 1 (STAT1) Inhibits Mitochondrial Biogenesis in Liver and Fatty Acid Oxidation in Adipocytes
The transcription factor STAT1 plays a central role in orchestrating responses to various pathogens by activating the transcription of nuclear-encoded genes that mediate the antiviral, the antigrowth, and immune surveillance effects of interferons and other cytokines. In addition to regulating gene expression, we report that STAT1-/- mice display increased energy expenditure and paradoxically decreased release of triglycerides from white adipose tissue (WAT). Liver mitochondria from STAT1-/- mice show both defects in coupling of the electron transport chain (ETC) and increased numbers of mitochondria. Consistent with elevated numbers of mitochondria, STAT1-/- mice expressed increased amounts of PGC1α, a master regulator of mitochondrial biogenesis. STAT1 binds to the PGC1α promoter in fed mice but not in fasted animals, suggesting that STAT1 inhibited transcription of PGC1α. Since STAT1-/-mice utilized more lipids we examined white adipose tissue (WAT) stores. Contrary to expectations, fasted STAT1-/- mice did not lose lipid from WAT. β-adrenergic stimulation of glycerol release from isolated STAT1-/- WAT was decreased, while activation of hormone sensitive lipase was not changed. These findings suggest that STAT1-/- adipose tissue does not release glycerol and that free fatty acids (FFA) re-esterify back to triglycerides, thus maintaining fat mass in fasted STAT1-/- mice
Migraine and restless legs syndrome: is there an association?
Occasional clinical reports have suggested a link between migraine and restless legs syndrome. We undertook a systematic review of the evidence, which supports this association, and consider possible shared pathogenic mechanisms and the implications for current clinical practice
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Neuroinflammation and protein aggregation co-localize across the frontotemporal dementia spectrum.
The clinical syndromes of frontotemporal dementia are clinically and neuropathologically heterogeneous, but processes such as neuroinflammation may be common across the disease spectrum. We investigated how neuroinflammation relates to the localization of tau and TDP-43 pathology, and to the heterogeneity of clinical disease. We used PET in vivo with (i) 11C-PK-11195, a marker of activated microglia and a proxy index of neuroinflammation; and (ii) 18F-AV-1451, a radioligand with increased binding to pathologically affected regions in tauopathies and TDP-43-related disease, and which is used as a surrogate marker of non-amyloid-β protein aggregation. We assessed 31 patients with frontotemporal dementia (10 with behavioural variant, 11 with the semantic variant and 10 with the non-fluent variant), 28 of whom underwent both 18F-AV-1451 and 11C-PK-11195 PET, and matched control subjects (14 for 18F-AV-1451 and 15 for 11C-PK-11195). We used a univariate region of interest analysis, a paired correlation analysis of the regional relationship between binding distributions of the two ligands, a principal component analysis of the spatial distributions of binding, and a multivariate analysis of the distribution of binding that explicitly controls for individual differences in ligand affinity for TDP-43 and different tau isoforms. We found significant group-wise differences in 11C-PK-11195 binding between each patient group and controls in frontotemporal regions, in both a regions-of-interest analysis and in the comparison of principal spatial components of binding. 18F-AV-1451 binding was increased in semantic variant primary progressive aphasia compared to controls in the temporal regions, and both semantic variant primary progressive aphasia and behavioural variant frontotemporal dementia differed from controls in the expression of principal spatial components of binding, across temporal and frontotemporal cortex, respectively. There was a strong positive correlation between 11C-PK-11195 and 18F-AV-1451 uptake in all disease groups, across widespread cortical regions. We confirmed this association with post-mortem quantification in 12 brains, demonstrating strong associations between the regional densities of microglia and neuropathology in FTLD-TDP (A), FTLD-TDP (C), and FTLD-Pick's. This was driven by amoeboid (activated) microglia, with no change in the density of ramified (sessile) microglia. The multivariate distribution of 11C-PK-11195 binding related better to clinical heterogeneity than did 18F-AV-1451: distinct spatial modes of neuroinflammation were associated with different frontotemporal dementia syndromes and supported accurate classification of participants. These in vivo findings indicate a close association between neuroinflammation and protein aggregation in frontotemporal dementia. The inflammatory component may be important in shaping the clinical and neuropathological patterns of the diverse clinical syndromes of frontotemporal dementia
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