ObjectiveWe investigated the reliability and accuracy of a bedside diagnostic algorithm for patients presenting with vertigo/unsteadiness to the emergency department.MethodsWe enrolled consecutive adult patients presenting with vertigo/unsteadiness at a tertiary hospital. STANDING, the acronym for the four-step algorithm we have previously described, based on nystagmus observation and well-known diagnostic maneuvers includes (1) the discrimination between SponTAneous and positional nystagmus, (2) the evaluation of the Nystagmus Direction, (3) the head Impulse test, and (4) the evaluation of equilibrium (staNdinG). Reliability of each step was analyzed by Fleiss’ K calculation. The reference standard (central vertigo) was a composite of brain disease including stroke, demyelinating disease, neoplasm, or other brain disease diagnosed by initial imaging or during 3-month follow-up.ResultsThree hundred and fifty-two patients were included. The incidence of central vertigo was 11.4% [95% confidence interval (CI) 8.2–15.2%]. The leading cause was ischemic stroke (70%). The STANDING showed a good reliability (overall Fleiss K 0.83), the second step showing the highest (0.95), and the third step the lowest (0.74) agreement. The overall accuracy of the algorithm was 88% (95% CI 85–88%), showing high sensitivity (95%, 95% CI 83–99%) and specificity (87%, 95% CI 85–87%), very high-negative predictive value (99%, 95% CI 97–100%), and a positive predictive value of 48% (95% CI 41–50%) for central vertigo.ConclusionUsing the STANDING algorithm, non-sub-specialists achieved good reliability and high accuracy in excluding stroke and other threatening causes of vertigo/unsteadiness.

BackgroundDelayed neuropsychological sequelae (DNS) commonly occur after recovery from acute carbon monoxide (CO) poisoning. The preventive role and the indications for hyperbaric oxygen therapy in the acute setting are still controversial. Early identification of patients at risk in the Emergency Department might permit an improvement in quality of care. We conducted a retrospective study to identify predictive risk factors for DNS development in the Emergency Department.MethodsWe retrospectively considered all CO-poisoned patients admitted to the Emergency Department of Careggi University General Hospital (Florence, Italy) from 1992 to 2007. Patients were invited to participate in three follow-up visits at one, six and twelve months from hospital discharge. Clinical and biohumoral data were collected; univariate and multivariate analysis were performed to identify predictive risk factors for DNS.ResultsThree hundred forty seven patients were admitted to the Emergency Department for acute CO poisoning from 1992 to 2007; 141/347 patients participated in the follow-up visit at one month from hospital discharge. Thirty four/141 patients were diagnosed with DNS (24.1%). Five/34 patients previously diagnosed as having DNS presented to the follow-up visit at six months, reporting a complete recovery. The following variables (collected before or upon Emergency Department admission) were associated to DNS development at one month from hospital discharge in the univariate analysis: CO exposure duration >6 hours, a Glasgow Coma Scale (GCS) score <9, seizures, systolic blood pressure <90 mmHg, elevated creatine phosphokinase concentration and leukocytosis. There was no significant correlation with age, sex, voluntary exposure, headache, transient loss of consciousness, GCS between 14 and 9, arterial lactate and carboxyhemoglobin concentration. The multivariate analysis confirmed as independent prognostic factors GCS <9 (OR 7.15; CI 95%: 1.04-48.8) and leukocytosis (OR 3.31; CI 95%: 1.02-10.71).ConclusionsOur study identified several potential predictive risk factors for DNS. Treatment algorithms based on an appropriate risk-stratification of patients in the Emergency Department might reduce DNS incidence; however, more studies are needed. Adequate follow-up after hospital discharge, aimed at correct recognition of DNS, is also important.

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Huntington’s disease is characterized by a complex and heterogeneous pathogenic profile. Studies have shown that disturbance in lipid homeostasis may represent a critical determinant in the progression of several neurodegenerative disorders. The recognition of perturbed lipid metabolism is only recently becoming evident in HD. In order to provide more insight into the nature of such a perturbation and into the effect its modulation may have in HD pathology, we investigated the metabolism of Sphingosine-1-phosphate (S1P), one of the most important bioactive lipids, in both animal models and patient samples. Here, we demonstrated that S1P metabolism is significantly disrupted in HD even at early stage of the disease and importantly, we revealed that such a dysfunction represents a common denominator among multiple disease models ranging from cells to humans through mouse models. Interestingly, the in vitro anti-apoptotic and the pro-survival actions seen after modulation of S1P-metabolizing enzymes allows this axis to emerge as a new druggable target and unfolds its promising therapeutic potential for the development of more effective and targeted interventions against this incurable condition.

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It has been a long trip from 1992, the year of the discovery of MECP2, to the present day. What is surprising is that some of the pivotal roles of MeCP2 were already postulated at that time, such as repression of inappropriate expression from repetitive elements and the regulation of pericentric heterochromatin condensation. However, MeCP2 performs many more functions. MeCP2 is a reader of epigenetic information contained in methylated (and hydroxymethylated) DNA, moving from the 'classical' CpG doublet to the more complex view addressed by the non-CpG methylation, which is a feature of the postnatal brain. MECP2 is a transcriptional repressor, although when it forms complexes with the appropriate molecules, it can become a transcriptional activator. For all of these aspects, Rett syndrome, which is caused by MECP2 mutations, is considered a paradigmatic example of a 'chromatin disorder'. Even if the hunt for bona-fide MECP2 target genes is far from concluded today, the role of MeCP2 in the maintenance of chromatin architecture appears to be clearly established. Taking a cue from the non-scientific literature, we can firmly attest that MeCP2 is a player with 'a great future behind it'*.*V. Gassmann 'Un grande avvenire dietro le spalle'. TEA Eds.

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Objective: To validate a clinical diagnostic tool, used by emergency physicians (EPs), to diagnose the central cause of patients presenting with vertigo, and to determine interrater reliability of this tool. Methods: A convenience sample of adult patients presenting to a single academic ED with isolated vertigo (i.e. vertigo without other neurological deficits) was prospectively evaluated with STANDING (SponTAneous Nystagmus, Direction, head Impulse test, standiNG) by five trained EPs. The first step focused on the presence of spontaneous nystagmus, the second on the direction of nystagmus, the third on head impulse test and the fourth on gait. The local standard practice, senior audiologist evaluation corroborated by neuroimaging when deemed appropriate, was considered the reference standard. Sensitivity and specificity of STANDING were calculated. On the first 30 patients, inter-observer agreement among EPs was also assessed. Results: Five EPs with limited experience in nystagmus assessment volunteered to participate in the present study enrolling 98 patients. Their average evaluation time was 9.9 ± 2.8 min (range 6-17). Central acute vertigo was suspected in 16 (16.3%) patients. There were 13 true positives, three false positives, 81 true negatives and one false negative, with a high sensitivity (92.9%, 95% CI 70-100%) and specificity (96.4%, 95% CI 93-38%) for central acute vertigo according to senior audiologist evaluation. The Cohen's kappas of the first, second, third and fourth steps of the STANDING were 0.86, 0.93, 0.73 and 0.78, respectively. The whole test showed a good inter-observer agreement (k = 0.76, 95% CI 0.45-1). Conclusions: In the hands of EPs, STANDING showed a good interobserver agreement and accuracy validated against the local standard of care.