Ethical challenges in tracheostomy-assisted ventilation in amyotrophic lateral sclerosis

Author's accepted version (post-print).This is a post-peer-review, pre-copyedit version of an article published in Journal of Neurology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00415-018-9054-x.Available from 15/09/2019.acceptedVersio

Posterior circulation stroke diagnosis using HINTS in patients presenting with acute vestibular syndrome: A systematic review

PurposeAcute vestibular syndrome – vertigo, nausea/vomiting, nystagmus and gait unsteadiness – is common, and differentiating posterior circulation stroke from a peripheral cause can be challenging. The National Institute of Health Stroke Scale (NIHSS) does not include acute vestibular syndrome, and early computed tomography scanning cannot rule out acute ischaemia. A positive Head Impulse–Nystagmus–Test of Skew (HINTS) test suggests posterior circulation stroke in acute vestibular syndrome when any of three signs are present: normal horizontal head impulse, gaze-direction nystagmus or eye skew deviation. This systematic review examined the accuracy of positive HINTS in identifying posterior circulation stroke in acute vestibular syndrome patients.MethodsWe searched MEDLINE (1966 to 21 December 2017), EMBASE (1980 to December 2017), Web of Science and scanned bibliographies. Two authors independently screened relevant articles and extracted data. We included studies where HINTS was used to identify posterior circulation stroke with diagnosis confirmed using magnetic resonance imaging.FindingsSix studies (n = 644 patients) were identified. Acute stroke was confirmed in 200 (31.1%) patients. There was a 15-fold increased risk of posterior circulation stroke in patients with positive HINTS test compared to those with no abnormality (RR: 15.84, 95% CI: 5.25–47.79). For any stroke, the pooled sensitivity was 95.5% (95% CI: 92.6–98.4%) and specificity was 71.2% (95% CI: 67.0–75.4%).Discussion and ConclusionThe data suggest that the HINTS test as one element of clinical evaluation is useful to differentiate posterior circulation stroke from peripheral causes in acute vestibular syndrome. Further studies are needed to validate HINTS as a clinical prediction tool in emergency department settings and selection of patients for reperfusion treatment

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

X-linked adrenoleukodystrophy in Norway Clinical and epidemiological aspects

In this thesis for the degree of PhD, cand.med. Morten Andreas Horn and his coworkers have surveyed the Norwegian population of patients with X-linked adrenoleukodystrophy. Their findings contribute to our knowledge of the prevalence and incidence of X-ALD, as well as the rate of new mutations among newborns. The researchers gained new knowledge about the severity and progression of X-ALD among males and females, and describe a pattern of age-dependent penetrance. On the other hand, cases with mild phenotypes are also found, and may be more important if newborn screening for X-ALD is introduced. A separate paper describes small nerve fiber involvement in X-ALD patients, a finding not previously reported

Milde phenotype in an adult male With X-linked adrenoleukodystrophy

Key Clinical Message:X-linked adrenoleukodystrophy may present with a deceptively mild phenotype, even in adult males. Tight collaboration between clinicians, geneticists, biochemists, and other specialists is increasingly required for clarification of diagnosis in cases with atypical presentation

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n similar to 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n similar to 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders