Missense mutations at homologous positions in the fourth and fifth laminin A G-like domains of eyes shut homolog cause autosomal recessive retinitis pigmentosa

Purpose: To describe two novel mutations in the eyes shut homolog (EYS) gene in two families with autosomal recessive retinitis pigmentosa (arRP) from Pakistan and Indonesia. Methods: Genome-wide linkage and homozygosity mapping were performed using single nucleotide polymorphism microarray analysis in affected members of the two arRP families. Sequence analysis was performed to identify genetic changes in protein coding exons of EYS. Results: In the Indonesian and Pakistani families, homozygous regions encompassing the EYS gene at 6q12 were identified, with maximum LOD scores of 1.8 and 3.6, respectively. Novel missense variants in the EYS gene (p.D2767Y and p.D3028Y) were found in the Pakistani and Indonesian families, respectively, that co-segregate with the disease phenotype. Interestingly, the missense variants are located at the same homologous position within the fourth and fifth laminin A G-like domains of EYS. Conclusions: To date, mostly protein-truncating mutations have been described in EYS, while only few patients have been described with pathogenic compound heterozygous missense mutations. The mutations p.D2767Y and p.D3028Y described in this study affect highly conserved residues at homologous positions in laminin A G-like domains and support the notion that missense mutations in EYS can cause arRP

Circle of Willis variation in a complex stroke presentation: a case report

BACKGROUND: The impact of circle of Willis anatomical variation upon the presentation of stroke is probably underrecognised. CASE PRESENTATION: A 63-year-old right-handed woman developed a left hemiparesis and right leg weakness sequentially following a road traffic accident (RTA). Despite initial concern about the possibility of cervical spinal cord injury, the final diagnosis was bilateral artery-to-artery embolic cerebral infarction with dominant right internal carotid artery. CONCLUSION: The case illustrates the complex presentation of stroke as a pseudo-cervical cord lesion and the impact of circle of Willis anatomical variation upon the expression of large vessel cerebrovascular disease

Structural Complications Following ST-Elevation Myocardial Infarction: An Analysis of the National Inpatient Sample 2016 to 2020

ST-elevation myocardial infarction (STEMI) is a life-threatening emergency that can result in cardiac structural complications without timely revascularization. A retrospective study from the National Inpatient Sample included all patients with a diagnosis of STEMI between 2016 and 2020. Primary outcomes of interest were in-hospital mortality, length of stay (LoS), and healthcare costs for patients with and without structural complications. There were 994,300 hospital admissions included in the analysis (median age 64 years and 32.2% female). Structural complications occurred in 0.78% of patients. There was a three-fold increase in patients with cardiogenic shock (41.6% vs. 13.6%) and in-hospital mortality (30.6% vs. 10.7%) in the group with structural complications. The median LoS was longer (5 days vs. 3 days), and the median cost was significantly greater (USD 32,436 vs. USD 20,241) for patients with structural complications. After adjustments, in-hospital mortality was significantly greater for patients with structural complications (OR 1.99, 95% CI 1.73-2.30), and both LoS and costs were greater. There was a significant increase in mortality with ruptured cardiac wall (OR 9.16, 95% CI 5.91-14.20), hemopericardium (OR 3.20, 95% CI 1.91-5.35), and ventricular septal rupture (OR 2.57, 95% CI 1.98-3.35) compared with those with no complication. In conclusion, structural complications in STEMI patients are rare but potentially catastrophic events

Radiomic markers of intracerebral hemorrhage expansion on non-contrast CT: independent validation and comparison with visual markers

Objective: To devise and validate radiomic signatures of impending hematoma expansion (HE) based on admission non-contrast head computed tomography (CT) of patients with intracerebral hemorrhage (ICH). Methods: Utilizing a large multicentric clinical trial dataset of hypertensive patients with spontaneous supratentorial ICH, we developed signatures predictive of HE in a discovery cohort (n = 449) and confirmed their performance in an independent validation cohort (n = 448). In addition to n = 1,130 radiomic features, n = 6 clinical variables associated with HE, n = 8 previously defined visual markers of HE, the BAT score, and combinations thereof served as candidate variable sets for signatures. The area under the receiver operating characteristic curve (AUC) quantified signatures’ performance. Results: A signature combining select radiomic features and clinical variables attained the highest AUC (95% confidence interval) of 0.67 (0.61–0.72) and 0.64 (0.59–0.70) in the discovery and independent validation cohort, respectively, significantly outperforming the clinical (pdiscovery = 0.02, pvalidation = 0.01) and visual signature (pdiscovery = 0.03, pvalidation = 0.01) as well as the BAT score (pdiscovery < 0.001, pvalidation < 0.001). Adding visual markers to radiomic features failed to improve prediction performance. All signatures were significantly (p < 0.001) correlated with functional outcome at 3-months, underlining their prognostic relevance. Conclusion: Radiomic features of ICH on admission non-contrast head CT can predict impending HE with stable generalizability; and combining radiomic with clinical predictors yielded the highest predictive value. By enabling selective anti-expansion treatment of patients at elevated risk of HE in future clinical trials, the proposed markers may increase therapeutic efficacy, and ultimately improve outcomes

Impact of Scotland’s comprehensive, smoke-free legislation on stroke

&lt;p&gt;Background: Previous studies have reported a reduction in acute coronary events following smoke-free legislation. Evidence is lacking on whether stroke is also reduced. The aim was to determine whether the incidence of stroke, overalland by sub-type, fell following introduction of smoke-free legislation across Scotland on 26 March 2006.&lt;/p&gt; &lt;p&gt;Methods and Findings: A negative binomial regression model was used to determine whether the introduction of smokefree legislation resulted in a step and/or slope change in stroke incidence. The model was adjusted for age-group, sex, socioeconomic deprivation quintile, urban/rural residence and month. Interaction tests were also performed. Routine hospital administrative data and death certificates were used to identify all hospital admissions and pre-hospital deaths due to stroke (ICD10 codes I61, I63 and I64) in Scotland between 2000 and 2010 inclusive. Prior to the legislation, rates of all stroke, intracerebral haemorrhage and unspecified stroke were decreasing, whilst cerebral infarction was increasing at 0.97% per annum. Following the legislation, there was a dramatic fall in cerebral infarctions that persisted for around 20 months. No visible effect was observed for other types of stroke. The model confirmed an 8.90% (95% CI 4.85, 12.77, p,0.001) stepwise reduction in cerebral infarction at the time the legislation was implemented, after adjustment for potential cofounders.&lt;/p&gt; &lt;p&gt;Conclusions: Following introduction of national, comprehensive smoke-free legislation there was a selective reduction in cerebral infarction that was not apparent in other types of stroke.&lt;/p&gt

Brain herniation in a patient with apparently normal intracranial pressure: a case report

Introduction Intracranial pressure monitoring is commonly implemented in patients with neurologic injury and at high risk of developing intracranial hypertension, to detect changes in intracranial pressure in a timely manner. This enables early and potentially life-saving treatment of intracranial hypertension. Case presentation An intraparenchymal pressure probe was placed in the hemisphere contralateral to a large basal ganglia hemorrhage in a 75-year-old Caucasian man who was mechanically ventilated and sedated because of depressed consciousness. Intracranial pressures were continuously recorded and never exceeded 17 mmHg. After sedation had been stopped, our patient showed clinical signs of transtentorial brain herniation, despite apparently normal intracranial pressures (less than 10 mmHg). Computed tomography revealed that the size of the intracerebral hematoma had increased together with significant unilateral brain edema and transtentorial herniation. The contralateral hemisphere where the intraparenchymal pressure probe was placed appeared normal. Our patient underwent emergency decompressive craniotomy and was tracheotomized early, but did not completely recover. Conclusions Intraparenchymal pressure probes placed in the hemisphere contralateral to an intracerebral hematoma may dramatically underestimate intracranial pressure despite apparently normal values, even in the case of transtentorial brain herniation

Carotid bruits as predictor for carotid stenoses detected by ultrasonography: an observational study

<p>Abstract</p> <p>Background</p> <p>Carotid surgery in asymptomatic subjects with carotid stenosis is effective to prevent ischemic stroke. There is, however, uncertainty how to find such persons at risk, because mass screening with carotid artery ultrasonography (US) is not cost-effective. Signs of carotid bruits corresponding to the carotid arteries may serve as a tool to select subjects for further investigation. This study is thus aimed at determining the usefulness of carotid bruits in the screening of carotid stenoses.</p> <p>Methods</p> <p>1555 consecutive carotid ultrasonography investigations from 1486 cases done between January 2004 and March 2006 at Norrlands University Hospital, Sweden, were examined. 356 subjects, medium age 69 (27–88) years, had a significant (≥ 50%) US-verified carotid stenosis uni- or bilaterally, 291 had been examined for signs of carotid bruits. The likelihood ratios for carotid bruits to predict US-verified carotid stenoses were calculated and expressed as likelihood percentages.</p> <p>Results</p> <p>Thirty-one out of 100 persons (31%) with carotid bruit as an indication to perform carotid US had a significant (≥ 50%) carotid stenosis. 281 of the 356 (79%) cases with significant carotid stenoses were found among patients with cerebrovascular disease (CVD). 145 of 226 (64%) CVD patients with a significant carotid stenosis had a carotid bruit. In patients with 50–99% carotid stenoses carotid bruits had an accuracy of 75% (436/582), a sensitivity of 71% (236/334), a specificity of 81% (200/248), a positive likelihood ratio at 3.65 and a negative likelihood at 0.36. Patients with 70–99% stenoses had the highest sensitivity at 77% (183/238). In patients with 100% carotid stenoses, carotid bruits had a sensitivity of 26% (15/57) and a specificity of 49% (256/525).</p> <p>Conclusion</p> <p>Although carotid bruits are not accurate to confirm or to exclude significant carotid stenoses, these signs are appropriate for directed screening for further investigation with carotid US if the patient lacks contraindications for surgery. Lack of carotid bruits in CVD patients does not exclude a carotid stenosis.</p

Protocol for a prospective collaborative systematic review and meta-analysis of individual patient data from randomised controlled trials of vasoactive drugs in acute stroke: the Blood pressure in Acute Stroke Collaboration, stage-3 (BASC-3)

Rationale Despite several large clinical trials assessing blood pressure lowering in acute stroke, equipoise remains, particularly for ischaemic stroke. The ‘Blood pressure in Acute Stroke Collaboration’ (BASC) commenced in the mid 1990s focusing on systematic reviews and meta-analysis of blood pressure lowering in acute stroke. From the start, BASC planned to assess safety and efficacy of blood pressure lowering in acute stroke using individual patient data. Aims To determine the optimal management of blood pressure in patients with acute stroke, encompassing both intracerebral haemorrhage and ischaemic stroke. Secondary aims are to assess which clinical and therapeutic factors may alter the optimal management of high blood pressure in patients with acute stroke and to assess the effect of vasoactive treatments on haemodynamic variables. Methods and design Individual patient data from randomised controlled trials of blood pressure management in participants with ischaemic stroke and/or intracerebral haemorrhage enrolled during the ultra-acute (pre-hospital), hyper-acute (<6 hours), acute (<48 hours) and sub-acute (<168 hours) phases of stroke. Study outcomes The primary effect variable will be functional outcome defined by the ordinal distribution of the modified Rankin Scale; analyses will also be carried out in prespecified subgroups to assess the modifying effects of stroke-related and pre-stroke patient characteristics. Key secondary variables will include clinical, haemodynamic and neuroradiological variables; safety variables will comprise death and serious adverse events. Discussion Study questions will be addressed in stages, according to the protocol, before integrating these into a final overreaching analysis. We invite eligible trials to join the collaboration