Transoesophageal Echocardiographic - Defined Valvular Strands in Acute Ischaemic Stroke: A Prospective Study

Background: Transoesophageal echocardiographic (TOE)-defined mobile, thread-like valvular strands (VS) have been associated with acute ischaemic stroke (AIS). The relationship between VS as a possible embolic substrate and the risk of recurrent stroke remains unclear. Our primary aims were to measure the prevalence of VS and explore their association with AIS in a case-control study and then, compare the risk of subsequent poor vascular outcome (vascular events and vascular death) in the stroke cohort patients with or without VS in a follow-up study. Our secondary aims were to determine the relationship of VS to other potential cardiac sources of emboli in TOE, relationship of VS to diastolic dysfunction in stroke cohort on comparison with controls. In addition, we sought to evaluate the relationship of VS to ischaemic stroke subtype and infarct topography on neuroimaging, and also to determine the relationship of hypercoagulable states in young patients with VS in the stroke cohort. Methods: In the case-control study, the prevalence of VS was estimated from patients consecutively admitted with AIS and from patients underwent TOE for cardiac conditions (those with infective endocarditis and stroke were excluded) in our institution over a two year period. In the follow-up study, patients with AIS were followed to evaluate the risk of poor vascular outcome, including risk of recurrent stroke. Results: We recruited 170 patients with AIS and of those, 78 underwent TOE. In our case-control study, we found TOE-defmed VS in approximately half of the patients with AIS (38/78, 48.7%) compared to one-third of controls (29/89, 32.6%). VS were more commonly seen in stroke patients over the age of 60 years (21/34, 61.8%). Univariate analysis found an association between the presence of VS and risk of AIS (OR = 3.85 ,p = 0.05), but multivariate analysis reduced the strength of the association (OR = 2.15,p= 0.06). In stroke subtypes, high prevalence of VS was seen in cardioembolic stroke but it did not reach statistical significance (p = 0.52) and there was no increased frequency of VS in cryptogenic stroke subtype. Diastolic dysfunction was seen in 78.9 % of cases with VS and there was a strong association between diastolic dysfunction and VS in the case-control study (OR 7.75,/) = 0.005). There was no statistically significant association between infarct location (cortical, subcortical, brainstem or cerebellar) in neuroimaging and the presence of VS. There were only few young cases with abnormalities in laboratory testing for hypercoagulable conditions. The risk of recurrent stroke and survival without poor vascular outcome was not statistically different between cases with or without VS in our study (OR = 1.45, 95 % Cl 0.30 - 6.96,p = 0.64). Conclusion: We were able to demonstrate an association between valvular strands and acute ischaemic stroke in our case-control study, however, the strength of the association was reduced after multivariate analysis. We did not find any increased risk of poor vascular outcome or increased recurrent stroke risk in cases with or without VS. Our findings do not support the embolic potential of valvular strands and it may not be a risk factor for stroke

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Teaching Video NeuroImages: Vagoglossopharyngeal neuralgia mimicking a seizure.

A 79-year-old woman with a history of partial thyroidectomy for multinodular goiter presented with acute onset episodic left ear pain followed by collapse with loss of awareness and limb jerking. Video EEG captured stereotyped episodes (video, links.lww.com/WNL/A287) with corresponding bradycardia and asystole for several seconds without ictal changes. A diagnosis of vagoglossopharyngeal neuralgia was made. She became symptom-free with eslicarbazepine and pacemaker insertion. Approximately 10% of patients with glossopharyngeal neuralgia experience bradycardia and syncope. Activation of the vagus nerve (dorsal motor nucleus) by excessive input from the glossopharyngeal nerve (via tractus solitarius) may lead to potential cardiac arrhythmias.</p

Effects of trail pheromone purity, dose, and type of placement on recruiting European fire ants, Myrmica rubra, to food baits

Trail pheromones of ants guide nest mates to a food source. Applications of synthetic trail pheromone could guide ants to poisoned food baits, which may expedite the demise of nests and help control invasive ant species. The trail pheromone of the invasive European fire ant (EFA), Myrmica rubra Linnaeus (Hymenoptera: Formicidae), has previously been identified as 3-ethyl-2,5- dimethylpyrazine. To facilitate its development as an operational EFA control tactic, our objectives were to determine the effects of (1) pheromone purity (isometrically pure or isomeric mixture), (2) pheromone dose [2, 20, 200, 2,000 ant equivalents (AEs)], and (3) type of pheromone placement (pheromone encircling a food source rather than leading towards it) on ant recruitment to baits. In laboratory binary choice experiments, isomerically pure and impure trail pheromone prompted similar recruitment responses of ants. The presence of pheromone, irrespective of dose, enhanced the recruitment of ants to food baits, with the dose of 200 AEs eliciting the strongest recruitment responses (2 AEs: 61% of foraging ants; 20 AEs: 57%; 200 AEs: 69%; 2000 AEs: 59%). Pheromone applied in a line leading towards the food bait, but not in a circle surrounding a food bait, was effective in recruiting ants, suggesting that 3-ethyl-2,5-dimethylpyrazine has a guiding but not an attractive function to EFAs

Recurrent catamenial status epilepticus: Is it rare or an under recognized phenomenon in women with epilepsy?

Recurrent catamenial status epilepticus may occur in generalized and focal epilepsy. Documenting the menstrual cycles and perimenstrual video-EEG help the diagnosis. Hormonal treatment including menstrual suppressive therapies may be used.</p

Identification of early indicators of altered metabolism in normal development using a rodent model system

10.1242/dmm.031815DMM Disease Models and Mechanisms1133181

Compromised Factor-Dependent Transcription Termination in a nusA Mutant of Escherichia coli: Spectrum of Termination Efficiencies Generated by Perturbations of Rho, NusG, NusA, and H-NS Family Proteins ▿

The proteins NusA and NusG, which are essential for the viability of wild-type Escherichia coli, participate in various postinitiation steps of transcription including elongation, antitermination, and termination. NusG is required, along with the essential Rho protein, for factor-dependent transcription termination (also referred to as polarity), but the role of NusA is less clear, with conflicting reports that it both promotes and inhibits the process. In this study, we found that a recessive missense nusA mutant [nusA(R258C)] exhibits a transcription termination-defective (that is, polarity-relieved) phenotype, much like missense mutants in rho or nusG, but is unaffected for either the rate of transcription elongation or antitermination in λ phage. Various combinations of the rho, nusG, and nusA mutations were synthetically lethal, and the lethality was suppressed by expression of the N-terminal half of nucleoid protein H-NS. Our results suggest that NusA function is indeed needed for factor-dependent transcription termination and that an entire spectrum of termination efficiencies can be generated by perturbations of the Rho, NusG, NusA, and H-NS family of proteins, with the corresponding phenotypes extending from polarity through polarity relief to lethality