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

The trial of David Ferrier, November 1881: context, proceedings, and aftermath

In November 1881, the eminent physiologist and physician David Ferrier was prosecuted under the Cruelty to Animals Act 1876. The prosecution was raised by the Victoria Street Society, formerly known as the Society for the Protection of Animals Liable to Vivisection, through its activist founder, Frances Power Cobbe. This article examines the legislative context prior to Ferrier’s trial, the personalities involved in the prosecution, and its course and outcome. The resultant impact, both personal, on Cobbe and Ferrier, and professional, on experimental neurophysiology, is discussed, in particular the foundation of the Association for the Advancement of Medicine by Research (AAMR) and the provision of legal support for medical practitioners subject to litigation

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

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