Early electroencephalography in patients with Emergency Room diagnoses of suspected new-onset seizures: Diagnostic yield and impact on clinical decision-making

AbstractPurposeTo assess the utility of acute electroencephalography (EEG) performed in the emergency room (ER) and its impact on subsequent management of patients with new-onset seizures. Adults who recover fully in the ER following suspected isolated new-onset seizures are usually discharged to the neurology clinic for further review. An EEG at that stage may be normal. We sought to assess the feasibility and yield of early EEG in the ER setting, its impact on management.MethodsA prospective study from January 2008 to January 2011 of patients diagnosed by ER physicians with uncomplicated suspected first episodes of unprovoked convulsive seizures. All patients underwent routine 30-min EEG in the ER prior to discharge and specialist review was arranged in the epilepsy clinic within 2 weeks of presentation. Management decisions were at the discretion of the treating neurologist. Seizure recurrence was assessed during a follow up period between 9 months and 3 years.Results136 patients were included in the study (92 males). Mean age was 32 years (range 16–73). Forty had abnormal EEGs: 16 focal epileptiform discharges, 12 focal slowing, 10 generalized spike-wave discharges and 2 generalized slowing. Using multivariate analysis, those with abnormal EEG (51% vs 11%, p=0.003) and abnormal MRI (53% vs 28%, p<0.001) were more likely to be commenced on anticonvulsant therapy. Abnormal MRI (p=0.001) was independently associated with a higher risk of recurrence.ConclusionsFollowing an ER diagnosis of new-onset uncomplicated seizure, early EEG had a high diagnostic yield. Abnormal EEG and abnormal MRI significantly contributed to decision-making regarding treatment at specialist review. Abnormal MRI was associated with significantly higher risks of subsequent seizures

Minding the gap and moving forward in children's long-term conditions: A vital role for health psychology.

Children with a long‐term condition and their families are confronted with multiple biopsychosocial challenges. In this editorial, we outline the scope of the problem and then look at some examples of interventions for children with a long‐term condition and how health psychology can inform and influence these. Health psychology theories are often not very well applied or reported, and there is considerable scope for more health psychology input in this area. We discuss relevant issues and suggest directions for future research in which health psychologists might apply subject‐specific theory and knowledge to further research and practice in the paediatric domain.Peer reviewe

Intracranial Stenting After Failed Thrombectomy in Patients With Moderately Severe Stroke: A Multicenter Cohort Study

Background and Purpose: Recently, acute intracranial stenting (ICS) has gained more interest as a potential bailout strategy for large vessel occlusions (LVO) that are refractory to thrombectomy. However, there are currently no reports on ICS in patients with moderately severe stroke discussing the question if implementing a permanent stent is feasible and leads to improved recanalization after failed thrombectomy. Methods: We analyzed a large multicenter database of patients receiving ICS for anterior circulation LVO after failed thrombectomy. Inclusion criteria were defined as: Moderately severe stroke (National Institute Health Stroke Scale (NIHSS) ≤9 on admission), anterior circulation LVO, acute ICS after failed stent retriever MT. Primary endpoint was the rate of improved successful recanalization after ICS defined as a modified Thrombolysis In cerebral Infarction (mTICI) score≥2b. Favorable neurological outcome was defined as an early neurological improvement (ENI) of 4 points or reaching 0 with respect to baseline NIHSS. Results: Forty-one patients met the inclusion criteria. A median of 2 retrievals were performed (IQR 1–4) prior decision-making for ICS. ICS led in 90.2% (37/41) of cases to a final mTICI≥2b with significant improvement (p < 0.001) after the last retrieval attempt. The median NIHSS decreased (p = 0.178) from 7 (IQR 3.5–8) on admission to 2.5 (IQR 0–8.25) at discharge. ENI was observed in 47.4% (18/38). sICH occurred in 4.8% (2/41). Conclusion: ICS after failed thrombectomy appears to effectively improve recanalization rates in patients with moderately severe strokes. Thus, ICS should be considered also for patients with baseline NIHSS ≤9 if thrombectomy fails

Functional aplasia of the contralateral A1 segment influences clinical outcome in patients with occlusion of the distal internal carotid artery

Background: The importance of an A1 aplasia remains unclear in stroke patients. In this work, we analyze the impact of an A1 aplasia contralateral to an acute occlusion of the distal internal carotid artery (ICA) on clinical outcomes. Methods: We conducted a retrospective study of consecutive stroke patients treated with mechanical thrombectomy at 12 tertiary care centers between January 2015 and February 2021 due to an occlusion of the distal ICA. Functional A1 aplasia was defined as the absence of A1 or hypoplastic A1 (>50% reduction to the contralateral site). Functional independence was measured by the modified Rankin Scale (mRS ≤ 2). Results: In total, 81 out of 1068 (8%) patients had functional A1 aplasia contralateral to distal ICA occlusion. Patients with functional contralateral A1 aplasia were more severely affected on admission (median NIHSS 18, IQR 15–23 vs. 17, IQR 13–21; aOR: 0.672, 95% CI: 0.448–1.007, p = 0.054) and post-interventional ischemic damage was larger (median ASPECTS 5, IQR 1–7, vs. 6, IQR 3–8; aOR: 1.817, 95% CI: 1.184–2.789, p = 0.006). Infarction occurred more often within the ipsilateral ACA territory (20/76, 26% vs. 110/961, 11%; aOR: 2.482, 95% CI: 1.389–4.437, p = 0.002) and both ACA territories (8/76, 11% vs. 5/961, 1%; aOR: 17.968, 95% CI: 4.979–64.847, p ≤ 0.001). Functional contralateral A1 aplasia was associated with a lower rate of functional independence at discharge (6/81, 8% vs. 194/965, 20%; aOR: 2.579, 95% CI: 1.086–6.122, p = 0.032) and after 90 days (5/55, 9% vs. 170/723, 24%; aOR: 2.664, 95% CI: 1.031–6.883, p = 0.043). Conclusions: A functional A1 aplasia contralateral to a distal ICA occlusion is associated with a poorer clinical outcome

Advances in Carcinogenic Metal Toxicity and Potential Molecular Markers

Metal compounds such as arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel are classified as carcinogens affecting human health through occupational and environmental exposure. However, the underlying mechanisms involved in tumor formation are not well clarified. Interference of metal homeostasis may result in oxidative stress which represents an imbalance between production of free radicals and the system’s ability to readily detoxify reactive intermediates. This event consequently causes DNA damage, lipid peroxidation, protein modification, and possibly symptomatic effects for various diseases including cancer. This review discusses predominant modes of action and numerous molecular markers. Attention is paid to metal-induced generation of free radicals, the phenomenon of oxidative stress, damage to DNA, lipid, and proteins, responsive signal transduction pathways with major roles in cell growth and development, and roles of antioxidant enzymatic and DNA repair systems. Interaction of non-enzymatic antioxidants (carotenoids, flavonoids, glutathione, selenium, vitamin C, vitamin E, and others) with cellular oxidative stress markers (catalase, glutathione peroxidase, and superoxide dismutase) as well as certain regulatory factors, including AP-1, NF-κB, Ref-1, and p53 is also reviewed. Dysregulation of protective pathways, including cellular antioxidant network against free radicals as well as DNA repair deficiency is related to oncogenic stimulation. These observations provide evidence that emerging oxidative stress-responsive regulatory factors and DNA repair proteins are putative predictive factors for tumor initiation and progression

Whole-Genome Cartography of Estrogen Receptor α Binding Sites

Using a chromatin immunoprecipitation-paired end diTag cloning and sequencing strategy, we mapped estrogen receptor α (ERα) binding sites in MCF-7 breast cancer cells. We identified 1,234 high confidence binding clusters of which 94% are projected to be bona fide ERα binding regions. Only 5% of the mapped estrogen receptor binding sites are located within 5 kb upstream of the transcriptional start sites of adjacent genes, regions containing the proximal promoters, whereas vast majority of the sites are mapped to intronic or distal locations (>5 kb from 5′ and 3′ ends of adjacent transcript), suggesting transcriptional regulatory mechanisms over significant physical distances. Of all the identified sites, 71% harbored putative full estrogen response elements (EREs), 25% bore ERE half sites, and only 4% had no recognizable ERE sequences. Genes in the vicinity of ERα binding sites were enriched for regulation by estradiol in MCF-7 cells, and their expression profiles in patient samples segregate ERα-positive from ERα-negative breast tumors. The expression dynamics of the genes adjacent to ERα binding sites suggest a direct induction of gene expression through binding to ERE-like sequences, whereas transcriptional repression by ERα appears to be through indirect mechanisms. Our analysis also indicates a number of candidate transcription factor binding sites adjacent to occupied EREs at frequencies much greater than by chance, including the previously reported FOXA1 sites, and demonstrate the potential involvement of one such putative adjacent factor, Sp1, in the global regulation of ERα target genes. Unexpectedly, we found that only 22%–24% of the bona fide human ERα binding sites were overlapping conserved regions in whole genome vertebrate alignments, which suggest limited conservation of functional binding sites. Taken together, this genome-scale analysis suggests complex but definable rules governing ERα binding and gene regulation

P2Y12 inhibitors for the neurointerventionalist.

The use of antiplatelets is widespread in clinical practice. However, for neurointerventional procedures, protocols for antiplatelet use are scarce and practice varies between individuals and institutions. This is further complicated by the quantity of antiplatelet agents which differ in route of administration, dosage, onset of action, efficacy and ischemic and hemorrhagic complications. Clarifying the individual characteristics for each antiplatelet agent, and their associated risks, will increasingly become relevant as the practice of mechanical thrombectomy, stenting, coiling and flow diversion procedures grows. The aim of this review is to summarize the existing literature for the use of P2Y12 inhibitors in neurointerventional procedures, examine the quality of the evidence, and highlight areas in need of further research

Handedness as a marker of cerebral lateralization in children with and without autism

We employed a multiple case studies approach to investigate lateralization of hand actions in typically and atypically developing children between 4 and 5 years of age. We report on a detailed set of over 1200 hand actions made by four typically developing boys and four boys with autism. Participants were assessed for unimanual hand actions to both objects and the self (self-directed behaviors). Individual and group analyses suggest that typically developing children have a right hand dominance for hand actions to objects and a left hand dominance for hand actions for self-directed behaviors, revealing a possible dissociation for functional specialization of the left and right hemispheres respectively. Children with autism demonstrated mixed-handedness for both target conditions, consistent with the hypothesis that there is reduced cerebral specialization in these children. The findings are consistent with the view that observed lateralized motor action can serve as an indirect behavioral marker for evidence of cerebral lateralization

Incidence of acute cerebrovascular events in patients with rheumatic or calcific mitral stenosis: a systematic review and meta-analysis

Background Patients with mitral stenosis (MS) may be predisposed to acute cerebrovascular events (ACE) and peripheral thromboembolic events (TEE). Concomitant atrial fibrillation (AF), mitral annular calcification (MAC) and rheumatic heart disease (RHD) are independent risk factors. Our aim was to evaluate the incidence of ACEs in MS patients and the implications of AF, MAC, and RHD on thromboembolic risks. Methods This systematic review was registered on PROSPERO (CRD42021291316). Six databases were searched from inception to 19th December 2021. The clinical outcomes were composite ACE, ischaemic stroke/transient ischaemic attack (TIA), and peripheral TEE. Results We included 16 and 9 papers, respectively, in our qualitative and quantitative analyses. The MS cohort with AF had the highest incidence of composite ACE (31.55%; 95%CI 3.60-85.03; I 2 =99%), followed by the MAC (14.85%; 95%CI 7.21-28.11; I 2 =98%), overall MS (8.30%; 95%CI 3.45-18.63; I 2 =96%) and rheumatic MS population (4.92%; 95%CI 3.53-6.83; I 2 =38%). Stroke/TIA were reported in 29.62% of the concomitant AF subgroup (95%CI 2.91-85.51; I 2 =99%) and in 7.11% of the overall MS patients (95%CI 1.91-23.16; I 2 =97%). However, the heterogeneity of the pooled incidence of clinical outcomes in all groups, except the rheumatic MS group, were substantial and significant. The logit-transformed proportion of composite ACE increased by 0.0141 (95% CI 0.0111-0.0171; p<0.01) per year of follow-up. Conclusion In the MS population, MAC and concomitant AF are risk factors for the development of ACE. The scarcity of data in our systematic review reflects the need for further studies to explore thromboembolic risks in all MS subtypes