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Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Stroke is a major contributor to death and disability worldwide. Prior to modern therapy, post-stroke mortality was approximately 10% in the acute period, with nearly one-half of the patients developing moderate-to-severe disability. The most fundamental aspect of acute stroke management is "time is brain". In acute ischemic stroke, the primary therapeutic goal of reperfusion therapy, including intravenous recombinant tissue plasminogen activator (IV TPA) and/or endovascular thrombectomy, is the rapid restoration of cerebral blood flow to the salvageable ischemic brain tissue at risk for cerebral infarction. Several landmark endovascular thrombectomy trials were found to be of benefit in select patients with acute stroke caused by occlusion of the proximal anterior circulation, which has led to a paradigm shift in the management of acute ischemic strokes. In this modern era of acute stroke care, more patients will survive with varying degrees of disability post-stroke. A comprehensive stroke rehabilitation program is critical to optimize post-stroke outcomes. Understanding the natural history of stroke recovery, and adapting a multidisciplinary approach, will lead to improved chances for successful rehabilitation. In this article, we provide an overview on the evaluation and the current advances in the management of acute ischemic stroke, starting in the prehospital setting and in the emergency department, followed by post-acute stroke hospital management and rehabilitation.

Objectives: Investigating the development of acute thrombocytopenia, differential etiologies, and potentially the rare manifestation of disseminated intravascular coagulation after brain tumor resection of primary and secondary malignancies., Materials and Methods: We performed a retrospective review of a case series of post-operative neurosurgical patients which developed thrombocytopenia. We applied National Library of Medicine search engine methodology using the terms disseminated intravascular coagulation and brain tumors., Results: We report clinical, radiographic, and laboratory data of four Neurointensive care unit patients that developed thrombocytopenia, three with disseminated intravascular coagulation after craniotomy, and one with heparin-induced thrombocytopenia masquerading as low grade disseminated intravascular coagulation. All four patients presented with cranial lesions and underwent neurosurgical resection. Underlying disorders included: high grade glioma, stage IV lung cancer with metastases, and meningioma. One patient survived and was able to recover after several days of hospitalization, while another patient was discharged to hospice. Search results illustrated that disseminated intravascular coagulation in the presence of glioblastoma multiforme is rare (only four patients) and may be due to a release of coagulation factors like tissue plasminogen activator, treated with antifibrinolytic agents. Searching the terms disseminated intravascular coagulation and brain tumors in the National Library of Medicine search engine yielded 116 results; eight were relevant to our study., Conclusions: Correlation of thrombocytopenia after neurosurgery for glioblastoma multiforme and disseminated intravascular coagulation is rare. It is extremely challenging to manage these patients with concomitant deep vein thrombosis/pulmonary embolism and intracranial bleeding. Heparin-induced thrombocytopenia is common yet possesses a different hematological coagulation profile and has more pharmacologic options. Neurointensive care unit teams should recognize intraoperative and post-operative disseminated intravascular coagulation cases, and heparin-induced thrombocytopenia in the differential of post-operative thrombocytopenia with specific pharmacologic interventions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Unruptured intracranial aneurysms (UIAs) are commonly acquired vascular lesions that form an outpouching of the arterial wall due to wall thinning. The prevalence of UIAs in the general population is 3.2%. In contrast, an intracranial aneurysm may be manifested after rupture with classic presentation of a thunderclap headache suggesting aneurysmal subarachnoid hemorrhage (SAH). Previous consensus suggests that although small intracranial aneurysms (<7 mm) are less susceptible to rupture, aneurysms larger than 7 mm should be treated on a case-by-case basis with consideration of additional risk factors of aneurysmal growth and rupture. However, this distinction is outdated. The PHASES score, which comprises data pooled from several prospective studies, provides precise estimates by considering not only the aneurysm size but also other variables, such as the aneurysm location. The International Study of Unruptured Intracranial Aneurysms is the largest observational study on the natural history of UIAs, providing the foundation to the current guidelines for the management of UIAs. Although SAH accounts for only 3% of all stroke subtypes, it is associated with considerable burden of morbidity and mortality. The initial management is focused on stabilizing the patient in the intensive care unit with close hemodynamic and serial neurologic monitoring with endovascular or open surgical aneurysm treatment to prevent rebleeding. Since the results of the International Subarachnoid Aneurysm Trial, treatment of aneurysmal SAH has shifted from surgical clipping to endovascular coiling, which demonstrated higher odds of survival free of disability at 1 year after SAH. Nonetheless, aneurysmal SAH remains a public health hazard and is associated with high rates of disability and death., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

More than eight decades after its discovery, routine electroencephalogram (EEG) remains a safe, noninvasive, inexpensive, bedside test of neurological function. Knowing when a routine EEG should be obtained while managing people with epilepsy is a critical aspect of optimal care. Despite advances in neuroimaging techniques that aid diagnosis of structural lesions in the central nervous system, EEG continues to provide critical diagnostic evidence with implications on treatment. A routine EEG performed after a first unprovoked seizure can support a clinical diagnosis of epilepsy and differentiate those without epilepsy, classify an epilepsy syndrome to impart prognosis, and characterize seizures for antiseizure management. Despite a current viral pandemic, EEG services continue, and the value of routine EEG is unchanged., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Summary: Long-term video-EEG monitoring has been the gold standard for diagnosis of epileptic and nonepileptic events. Medication changes, safety, and a lack of recording EEG in one's habitual environment may interfere with diagnostic representation and subsequently affect management. Some spells defy standard EEG because of ultradian and circadian times of occurrence, manifest nocturnal expression of epileptiform activity, and require classification for clarifying diagnostic input to identify optimal treatment. Some patients may be unaware of seizures, have frequent events, or subclinical seizures that require quantification before optimal management. The influence on antiseizure drug management and clinical drug research can be enlightened by long-term outpatient ambulatory EEG monitoring. With recent governmental shifts to focus on mobile health, ambulatory EEG monitoring has grown beyond diagnostic capabilities to target the dynamic effects of medical and nonmedical treatment for patients with epilepsy in their natural environment. Furthermore, newer applications in ambulatory monitoring include additional physiologic parameters (e.g., sleep, detection of myogenic signals, etc.) and extend treatment relevance to patients beyond seizure reduction alone addressing comorbid conditions. It is with this focus in mind that we direct our discussion on the present and future aspects of using ambulatory EEG monitoring in the treatment of patients with epilepsy., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 by the American Clinical Neurophysiology Society.)

Background: There is a paucity of literature regarding treatment options for extracranial pseudoaneurysms of the internal carotid artery (ICA). To date, Pipeline Embolization Device (PED; Medtronic Inc) use for the treatment of extracranial pseudoaneurysms of the ICA has only been reported from single-center case series., Objective: To evaluate the safety and efficacy of PED for the treatment of extracranial ICA pseudoaneurysms., Methods: This is a multicenter retrospective study involving 6 high-volume tertiary academic institutions in the United States. We analyzed patients with extracranial ICA pseudoaneurysms treated with PED between January 1, 2011, and January 1, 2019. Clinical assessment was performed pre- and postintervention using the modified Rankin Scale (mRS) and National Institution of Health Stroke Scale (NIHSS) at a minimum of 4-mo follow-up., Results: A total of 28 pseudoaneurysms with a mean diameter of 17.7 mm (range: 4.1-52.5 mm) were treated with PED in 24 patients at 6 participating centers. The mean age was 52.1 yr (17-73) ± 14.3 with 14 females and 10 males. At a mean of 21-mo (range 4-66 mo) follow-up, complete occlusion was achieved in 89% (n = 25/28), with near-complete occlusion (>90% occlusion) in the remainder. There were no periprocedural complications. Postprocedure NIHSS was 0 in 88% (n = 21/24) and 1 in 12% (n = 3/24) of patients, and mRS was 0 in 83% (n = 20/24) and 1 in 17% (n = 4/24) of patients., Conclusion: The treatment of extracranial ICA pseudoaneurysms with PED is safe and effective in selected patients. Randomized controlled trials and prospective cohort studies are needed to establish the role of flow diversion for ICA pseudoaneurysms., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Objectives: Patients with aneurysmal subarachnoid hemorrhage (aSAH) often sustain substantial cognitive and functional impairment. Traditional outcome measures have emphasized radiographic and gross clinical outcomes, but cognitive and functional outcomes are less frequently documented. This pilot study assessed the feasibility of administering longitudinal cognitive and neuropsychological testing and tracked patterns of functional improvement in aSAH patients., Patients and Methods: Standardized cognitive and neuropsychological testing were administered to a prospective cohort of aSAH patients admitted for treatment to our tertiary care center. Thirty consecutive aSAH patients (Hunt and Hess score 1-3) were enrolled over 23-months and baseline evaluations were completed within 24-h after admission. Patients were followed prospectively after treatment (coiling or clipping) at 1-, 3-, 6-, and 12-months. Functional outcome measures included the Montreal Cognitive Assessment, the Neuropsychiatric Inventory-Questionnaire, and the Functional Activities Questionnaire., Results: Of the 30 patients, 23 (77%) followed-up at 3-months, 21 (70%) at 6-months, and 19 (63%) at 12-months. Improvement from baseline to follow-up at 12-months was noted for general cognitive function (p = .004), memory (p = .025), and executive function (p = .039), with the greatest improvement occurring within 6-months. Daily function also improved mostly within 6-months (p = .022) while changes in neuropsychological disturbances were insignificant from baseline to follow-up at 12-months (p = .216)., Conclusion: Standardized cognitive and neuropsychological testing provides metrics for evaluating functional outcomes following treatment of aSAH. The addition of a brief battery of tests to routine clinical and radiographic evaluations is feasible. The main limitations are related to practice and referral patterns, and future studies are needed to evaluate the impact of treatment modalities on functional outcomes., Competing Interests: Declaration of Competing Interest Authors report no competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To determine whether earlier hospital discharge is feasible and safe in selected patients with subarachnoid hemorrhage (SAH) using an outpatient "fast-track" protocol., Patients and Methods: We conducted a prospective quality improvement cohort study with the primary feasibility end point of patients with SAH deemed safe for discharge by treating team consensus. All patients received detailed education and outpatient transcranial Doppler monitoring; caregivers could contact the on-call team 24-7. Primary safety end points were adverse events after discharge and hospital readmission., Results: From January 1, 2010, to January 1, 2015, our center had 377 SAH diagnoses, of which 200 were included in the final cohort, 36 qualifying for fast-track early discharge. The 30-day readmission rate for fast-track patients was 11.0% (4 of 36) compared with 11.4% (18 of 164) for non-fast-track patients. The rate of delayed cerebral ischemia and stroke was 3% (1 of 36) in the fast-track group vs 25.0% (41 of 164) for the non-fast-track group. Adverse events occurred in 11.0% (4 of 36) of the fast-track group compared with 26.0% (43 of 164) in the non-fast-track group. The mean length of stay was reduced 60% from 15 days to 6.6 days in the fast-track group., Conclusion: Although our fast-track group was relatively small, data suggested early feasibility and safety in a carefully selected group of patients with SAH. Direct and indirect financial benefits of early discharge over a 5-year period were an estimated savings at least $864,000 in overall costs. A comparative effectiveness study is planned to replicate and validate these results using a larger multicenter design., (© 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

For elderly patients undergoing elective surgical procedures, preoperative evaluation of cognition is often overlooked. Patients may experience postoperative delirium (POD) and postoperative cognitive decline (POCD), especially those with certain risk factors, including advanced age. Preoperative cognitive impairment is a leading risk factor for both POD and POCD, and studies have noted that identifying these deficiencies is critical during the preoperative period so that appropriate preventive strategies can be implemented. Comprehensive geriatric assessment is a useful approach which evaluates a patient's medical, psycho-social, and functional domains objectively. Various screening tools are available for preoperatively identifying patients with cognitive impairment. The Enhanced Recovery After Surgery (ERAS) protocols have been discussed in the context of prehabilitation as an effort to optimize a patient's physical status prior to surgery and decrease the risk of POD and POCD. Evidence-based protocols are warranted to standardize care in efforts to effectively meet the needs of these patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aim: To evaluate five illustrative cases and perform a literature review to identify and describe a working approach to adult-onset white matter diseases (WMD)., State of the Art: Inherited WMD are a group of disorders often seen in childhood. In adulthood, progressive WMDs are rare, apart from the common nonspecific causes of hypertension and other cerebrovascular diseases. The pattern of WMDs on neuroimaging can be an important clue to the final diagnosis. Due to the adoption of a combined clinical-imaging-laboratory approach, WMD is becoming better recognised, in addition to the rapidly evolving field of genomics in this area., Clinical Implications: While paediatric WMDs have a well-defined and literature-based clinical-laboratory approach to diagnosis, adult-onset WMDs remain an important, pathologically diverse, radiographic phenotype, with different and distinct neuropathologies among the various subtypes of WMD. Adult-onset WMDs comprise a wide collection of both acquired and inherited aetiologies. While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neurological complications are emerging, we are as yet unaware of it causing WMD outside of post-anoxic changes. It is important to recognise WMD as a potentially undefined acquired or genetic syndrome, even when extensive full genome testing reveals variants of unknown significance., Future Directions: We propose a combined clinical-imaging-laboratory approach to WMD and continued exploration of acquired and genetic factors. Adult-onset WMD, even given this approach, can be challenging because hypertension is often comorbid. Therefore, we propose that undiagnosed patients with WMD be entered into multicentre National Organisation for Rare Diseases registries to help researchers worldwide make new discoveries that will hopefully translate into future cures.

Objective: The role of CT perfusion (CTP) in the management of patients with acute ischemic stroke (AIS) remains a matter of debate. The primary aim of this study was to evaluate the correlation between the areas of infarction and penumbra on CTP scans and functional outcome in patients with AIS., Methods: This was a retrospective review of 100 consecutively treated patients with acute anterior circulation ischemic stroke who underwent CT angiography (CTA) and CTP at admission between February 2011 and October 2014. On CTP, the volume of ischemic core and penumbra was measured using the Alberta Stroke Program Early CT Score (ASPECTS). CTA findings were also noted, including the site of occlusion and regional leptomeningeal collateral (rLMC) score. Functional outcome was defined by modified Rankin Scale (mRS) score obtained at discharge. Associations of CTP and CTA parameters with mRS scores at discharge were assessed using multivariable proportional odds logistic regression models., Results: The median age was 67 years (range 19-95 years), and the median NIH Stroke Scale score was 16 (range 2-35). In a multivariable analysis adjusting for potential confounding variables, having an infarct on CTP scans in the following regions was associated with a worse mRS score at discharge: insula ribbon (p = 0.043), perisylvian fissure (p < 0.001), motor strip (p = 0.007), M2 (p < 0.001), and M5 (p = 0.023). A worse mRS score at discharge was more common in patients with a greater volume of infarct core (p = 0.024) and less common in patients with a greater rLMC score (p = 0.004)., Conclusions: The results of this study provide evidence that several CTP parameters are independent predictors of functional outcome in patients with AIS and have potential to identify those patients most likely to benefit from reperfusion therapy in the treatment of AIS.

Neurology faces an increasing shortage of neurologists in the United States due to a growing demand for neurologic services. A 7% increase in the supply of neurologists is predicted from 2012 to 2025, whereas the demand will rise by 16%. An increase in the neurology workforce is critical to meet the demands, and a significant gender gap remains within the workforce that must be addressed to further ease the discrepancy between supply and demand. Individual, institutional, and societal factors contribute to this gender discrepancy and potentially result in the burnout or soft attrition of women from neurology. These factors, including earning disparity between male and female neurologists, one of the largest gaps in pay for any medical specialty, and the lack of representation at higher academic levels with only 12% (14 of 113) of neurology department chairs at academic medical centers being women, could lead to increased attrition of women from neurology. Identifying and mitigating these factors may help narrow the gender gap and increase the supply of neurologists to better meet future demand., (© 2019 American Academy of Neurology.)

Goal: Cerebral small vessel disease (CSVD) leads to cognitive decline, gait disturbances, mood changes, and an increased risk of stroke. The goal of this study is to describe the relationship between a composite radiographic CSVD score and all-cause mortality., Materials and Methods: Data were collected from a prospective registry of patients with and without cerebrovascular disease from November 2010 through April 2018. The radiographic Total CSVD Score (tSVD) ranges from 0 (minimal disease) to 4 (severe disease), based on detection of lacunar infarcts, cerebral microbleeds, perivascular spaces, and subcortical or periventricular white matter hyperintensities. All-cause mortality served as the primary endpoint. The independent relationship between CSVD burden and all-cause mortality was assessed using Cox regression models with significance being P < .05., Findings: Four hundred and forty-nine patients were included (mean age, 63 years; 50.1% [225 of 449] women). The hazard ratio for mortality significantly increased with advancing score (1.92, P = .014 score 1; 2.92, P < .001 score 2; 4.23, P < .001 combined scores 3 and 4). Significance remained despite adjustment for coexistent cerebrovascular risk factors aside from age., Conclusions: The clinically practical tSVD score may serve as a predictor for all-cause mortality in populations with high disease prevalence. Continued investigations are needed to better understand the effects of risk factor modification on mortality and pathogenesis with the goal of developing disease modifying therapies., (Copyright © 2019. Published by Elsevier Inc.)

Purpose of Review: To review the current evidence supporting the use of endovascular thrombectomy (EVT) for the treatment of acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO)., Recent Findings: Recent advances in AIS management by EVT have led to significant reduction in morbidity and mortality in selected patients with LVO within the anterior circulation. Until recently, use of EVT was strictly based on time criteria, within 4.5 to 12 h of symptom onset with many patients presenting with "wake-up" stroke who were not considered for EVT. The positive results of the DAWN and DEFUSE-3 trials have shown benefit in extending the therapeutic window for EVT to 24 and 16 h, respectively, after last known normal (LKN) time in the setting of large ischemic penumbra. These trials represent a paradigm shift in contemporary treatment of AIS, changing from a purely time-based decision to treat to an individualized decision based on clinical and radiographic findings of salvageable tissue. Overall, acute stroke management has evolved considerably over the years from intravenous thrombolysis to include EVT, with paralleled improvements in patient selection and thrombectomy devices. Since the results of the DAWN and DEFUSE-3, EVT is now considered the standard of care in select patients with anterior circulation LVO up to 24 h from LKN time. Despite these developments, post-stroke disability remains pervasive and further studies are warranted in establishing the role of EVT in posterior circulation and distal vessel occlusions, with need for development of new and effective techniques for revascularization of small vessels.

Objective: To compare all-cause mortality rates across the severity range of white matter hyperintensities (WMH)., Patients and Methods: Between October 26, 2010, and October 5, 2017, the ongoing Mayo Clinic Florida Familial Cerebrovascular Diseases Registry prospectively enrolled 1011 diverse participants with and without cerebrovascular disease. T2-weighted magnetic resonance imaging of the brain was used to evaluate WMH in 455 participants using the Fazekas scale. Fazekas deep WMH (FD) and periventricular WMH (FPV) scores (0-3 points) were assigned on the basis of WMH severity. Kaplan-Meier survival analyses, Cox proportional hazards models, and estimated hazard ratios compared survival rates across FD and FPV categories. The Fisher exact and χ 2 tests evaluated the relationship of categorical variables, and the Kruskal-Wallis test measured the relationship of continuous variables across FD and FPV categories. All tests were performed at a P<.05 significance level., Results: Over a median follow-up of 3.06 years (range, 0.00-6.96 years), 96 deaths occurred. Higher FD scores corresponded to a higher likelihood of mortality (P<.001). Participants with an FD score of 3 were 4.69 (95% CI, 2.60-8.46) times more likely to die compared with those with an FD score of 0. Participants with higher FPV scores had a higher likelihood of mortality (P<.001). Participants with an FPV score of 3 were 7.04 (95% CI, 3.39-14.62) times more likely to die compared with those with an FPV score of 0. Once adjusted, age and baseline functional status explained most of the survival differences among the FD scores., Conclusion: Associations between all-cause mortality rates across the severity range of WMH were observed in the Registry. Further studies are warranted to understand the clinical importance of WMH in other clinical populations., (Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Stroke is the cause of about 10% of all epilepsy and 55% of newly diagnosed seizures among the elderly. Although recent advances in acute stroke therapy have improved longevity, there has been a consequent rise in the prevalence of stroke-related epilepsy (STRE). Many clinical studies make a distinction between early (within 7 days of onset of stroke) and late (beyond 7 days of onset of stroke) seizures based on presumed pathophysiological differences. Although early seizures are thought to be the consequence of local metabolic disturbances without altered neuronal networks, late seizures are thought to occur when the brain has acquired a predisposition for seizures. Overall, STRE has a good prognosis, being well controlled by antiepileptic drugs. However, up to 25% of cases become drug resistant. STRE can also result in increased morbidity, longer hospitalization, greater disability at discharge and greater resource utilization. Additional controlled trials are needed to explore the primary and secondary prevention of STRE as well as to provide high-quality evidence on efficacy and tolerability of antiepileptic drugs to guide treatment of STRE. Robust pre-clinical and clinical prediction models of STRE are also needed to develop treatments to prevent the transformation of infarcted tissue into an epileptic focus., (© Published 2018. This article is a U.S. Government work and is in the public domain in the USA.)

Mild traumatic brain injury accounts for the majority of head injuries and has been correlated with neurodegeneration and dementia. While repetitive mild traumatic brain injury is highly correlated to neurodegeneration, the correlation of a single mild traumatic brain injury with neurodegeneration is still unclear. Because tau aggregates are the main form of mild traumatic brain injury induced pathology, toxic forms of tau protein most likely play a role in the development of post-mild traumatic brain injury neurodegeneration. Therefore, it becomes crucial to characterize the properties of soluble tau aggregates in single versus repetitive mild traumatic brain injury. Herein, we isolated tau oligomers from wild-type mice exposed to single or repetitive mild traumatic brain injury and characterized the tau aggregates at functional, biochemical and biophysical levels. We demonstrated that single versus repetitive mild traumatic brain injuries frequencies lead to the formation of different tau oligomeric polymorphisms. These polymorphisms express different long-term potentiation impairment potencies, toxicity potentials, morphologies and strain indicating properties. To our knowledge, this is the first evidence that soluble tau oligomers derived from single versus repetitive mild traumatic brain injuries form distinct polymorphisms that possibly correlate with the risk of neurodegeneration after mild traumatic brain injury., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Acute aneurysmal subarachnoid hemorrhage (SAH) is a medical and neurosurgical emergency from ruptured brain aneurysm. Aneurysmal SAH is identified on brain computed tomography (CT) as increased density of basal cisterns and subarachnoid spaces from acute blood products. Aneurysmal SAH-like pattern on CT appears as an optical illusion effect of hypodense brain parenchyma and/or hyperdense surrounding cerebral cisterns and blood vessels termed as "pseudo-subarachnoid hemorrhage" (pseudo-SAH)., Methods: We reviewed clinical, laboratory, and radiographic data of all SAH diagnoses between January 2013 and January 2018, and found subsets of nonaneurysmal SAH, originally suspected to be aneurysmal in origin. We performed a National Library of Medicine search methodology using terms "subarachnoid hemorrhage," "pseudo," and "non-aneurysmal subarachnoid hemorrhage" singly and in combination to understand the sensitivity, specificity, and precision of pseudo-SAH., Results: Over 5 years, 230 SAH cases were referred to our tertiary academic center and only 7 (3%) met the definition of pseudo-SAH. Searching the National Library of Medicine using subarachnoid hemorrhage yielded 27,402 results. When subarachnoid hemorrhage and pseudo were combined, this yielded 70 results and sensitivity was 50% (n = 35). Similarly, search precision was relatively low (26%) as only 18 results fit the clinical description similar to the 7 cases discussed in our series., Conclusions: Aneurysmal SAH pattern on CT is distinct from nonaneurysmal and pseudo-SAH patterns. The origin of pseudo-SAH terminology appears mostly tied to comatose cardiac arrest patients with diffuse dark brain Hounsfield units and cerebral edema, and is a potential imaging pitfall in acute medical decision-making., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Acute ischemic stroke (AIS) is among the leading causes of death and long-term disability. Intravenous tissue plasminogen activator has been the mainstay of acute therapy. Recently, several prospective randomized trials documented the value of endovascular revascularization in selected patients with large-vessel occlusion within the anterior circulation. This finding has led to a paradigm shift in the management of AIS, including wide adoption of noninvasive neuroimaging to assess vessel patency and tissue viability, with the supplemental and independent use of intravenous tissue plasminogen activator to improve clinical outcomes. In this article, we review the landmark studies on management of AIS and the current position on the diagnosis and management of AIS. The review also highlights the importance of early stabilization and prompt initiation of therapeutic interventions before, during, and after the diagnosis of AIS within and outside of the hospital., (Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

The roles of corticotrophin-releasing factor (CRF), opioid peptides, leptin and ghrelin in anorexia nervosa (AN) were discussed in this paper. CRF is the key mediator of the hypothalamo-pituitary-adrenal (HPA) axis and also acts at various other parts of the brain, such as the limbic system and the peripheral nervous system. CRF action is mediated through the CRF1 and CRF2 receptors, with both HPA axis-dependent and HPA axis-independent actions, where the latter shows nil involvement of the autonomic nervous system. CRF1 receptors mediate both the HPA axis-dependent and independent pathways through CRF, while the CRF2 receptors exclusively mediate the HPA axis-independent pathways through urocortin. Opioid peptides are involved in the adaptation and regulation of energy intake and utilization through reward-related behavior. Opioids play a role in the addictive component of AN, as described by the "auto-addiction opioids theory". Their interactions have demonstrated the psychological aspect of AN and have shown to prevent the functioning of the physiological homeostasis. Important opioids involved are β-lipotropin, β-endorphin and dynorphin, which interact with both µ and κ opioids receptors to regulate reward-mediated behavior and describe the higher incidence of AN seen in females. Moreover, ghrelin is known as the "hunger" hormone and helps stimulate growth hormone (GH) and hepatic insulin-like-growth-factor-1(IGF-1), maintaining anabolism and preserving a lean body mass. In AN, high levels of GH due to GH resistance along with low levels of IGF-1 are observed. Leptin plays a role in suppressing appetite through the inhibition of neuropeptide Y gene. Moreover, the CRF, opioid, leptin and ghrelin mechanisms operate collectively at the HPA axis and express the physiological and psychological components of AN. Fear conditioning is an intricate learning process occurring at the level of the hippocampus, amygdala, lateral septum and the dorsal raphe by involving three distinct pathways, the HPA axis-independent pathway, hypercortisolemia and ghrelin. Opioids mediate CRF through noradrenergic stimulation in association with the locus coeruleus. Furthermore, CRF's inhibitory effect on gonadotropin releasing hormone can be further explained by the direct relationship seen between CRF and opioids. Low levels of gonadotropin have been demonstrated in AN where only estrogen has shown to mediate energy intake. In addition, estrogen is involved in regulating µ receptor concentrations, but in turn both CRF and opioids regulate estrogen. Moreover, opioids and leptin are both an effect of AN, while many studies have demonstrated a causal relationship between CRF and anorexic behavior. Moreover, leptin, estrogen and ghrelin play a role as predictors of survival in starvation. Since both leptin and estrogen are associated with higher levels of bone marrow fat they represent a longer survival than those who favor the ghrelin pathway. Future studies should consider cohort studies involving prepubertal males and females with high CRF. This would help prevent the extrapolation of results from studies on mice and draw more meaningful conclusions in humans. Studies should also consider these mechanisms in post-AN patients, as well as look into what predisposes certain individuals to develop AN. Finally, due to its complex pathogenesis the treatment of AN should focus on both the pharmacological and behavioral perspectives.

This cross-cultural study explored along with various personality factors the relationship between laughter and disease prevalence. Previous studies have only determined the effect of laughter on various health dimensions, whereas, this study quantified the level of laughter that was beneficial or detrimental to health. There were a total of 730 participants between the ages of eighteen and thirty-nine years. 366 participants were from Aurangabad, India (AUR), and 364 participants were from Mississauga, Canada (MISS). The participants were provided a survey assessing demographics, laughter, lifestyle, subjective well-being, life satisfaction, emotional well-being and health dimensions. In AUR, a beneficial effect of laughter was mediated through moderate levels (level two) of laughter, whereas both low (level one) and high (level three) levels had no effect. Similarly, in MISS, the beneficial effect was mediated through level two, but a negative effect was also seen at level three. This could be attributable to a higher prevalence of bronchial asthma in western countries. Laughter was associated with emotional well-being in MISS and life satisfaction in AUR, providing cross cultural models to describe the interactions between laughter and disease. This study validated the correlation between emotional well-being and life satisfaction, with a stronger correlation seen in MISS, suggesting that individualists rely more on their emotional well-being to judge their life satisfaction. In conclusion, there is a benefit to clinicians to incorporate laughter history into their general medical history taking. Future research should consider developing mechanisms to explain the effects of level two, determine specific systemic effects and obtain more samples to generalize the cross cultural differences.