Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Background and Purpose- The purpose of these guidelines is to provide an up-to-date comprehensive set of recommendations in a single document for clinicians caring for adult patients with acute arterial ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators. These guidelines supersede the 2013 Acute Ischemic Stroke (AIS) Guidelines and are an update of the 2018 AIS Guidelines. Methods- Members of the writing group were appointed by the American Heart Association (AHA) Stroke Council's Scientific Statements Oversight Committee, representing various areas of medical expertise. Members were not allowed to participate in discussions or to vote on topics relevant to their relations with industry. An update of the 2013 AIS Guidelines was originally published in January 2018. This guideline was approved by the AHA Science Advisory and Coordinating Committee and the AHA Executive Committee. In April 2018, a revision to these guidelines, deleting some recommendations, was published online by the AHA. The writing group was asked review the original document and revise if appropriate. In June 2018, the writing group submitted a document with minor changes and with inclusion of important newly published randomized controlled trials with >100 participants and clinical outcomes at least 90 days after AIS. The document was sent to 14 peer reviewers. The writing group evaluated the peer reviewers' comments and revised when appropriate. The current final document was approved by all members of the writing group except when relationships with industry precluded members from voting and by the governing bodies of the AHA. These guidelines use the American College of Cardiology/AHA 2015 Class of Recommendations and Level of Evidence and the new AHA guidelines format. Results- These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks. The guidelines support the overarching concept of stroke systems of care in both the prehospital and hospital settings. Conclusions- These guidelines provide general recommendations based on the currently available evidence to guide clinicians caring for adult patients with acute arterial ischemic stroke. In many instances, however, only limited data exist demonstrating the urgent need for continued research on treatment of acute ischemic stroke.

Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

Plaguing humans for more than two millennia, manifest on every continent studied, and with more than one billion patients having an attack in any year, migraine stands as the sixth most common cause of disability on the planet. The pathophysiology of migraine has emerged from a historical consideration of the "humors" through mid-20th century distraction of the now defunct Vascular Theory to a clear place as a neurological disorder. It could be said there are three questions: why, how, and when? Why: migraine is largely accepted to be an inherited tendency for the brain to lose control of its inputs. How: the now classical trigeminal durovascular afferent pathway has been explored in laboratory and clinic; interrogated with immunohistochemistry to functional brain imaging to offer a roadmap of the attack. When: migraine attacks emerge due to a disorder of brain sensory processing that itself likely cycles, influenced by genetics and the environment. In the first, premonitory, phase that precedes headache, brain stem and diencephalic systems modulating afferent signals, light-photophobia or sound-phonophobia, begin to dysfunction and eventually to evolve to the pain phase and with time the resolution or postdromal phase. Understanding the biology of migraine through careful bench-based research has led to major classes of therapeutics being identified: triptans, serotonin 5-HT1B/1D receptor agonists; gepants, calcitonin gene-related peptide (CGRP) receptor antagonists; ditans, 5-HT1F receptor agonists, CGRP mechanisms monoclonal antibodies; and glurants, mGlu5 modulators; with the promise of more to come. Investment in understanding migraine has been very successful and leaves us at a new dawn, able to transform its impact on a global scale, as well as understand fundamental aspects of human biology.

Pathophysiology of Migraine: A Disorder of Sensory Processing

Considerable overlap has been identified in the risk factors, comorbidities and putative pathophysiological mechanisms of Alzheimer disease and related dementias (ADRDs) and type 2 diabetes mellitus (T2DM), two of the most pressing epidemics of our time Much is known about the biology of each condition, but whether T2DM and ADRDs are parallel phenomena arising from coincidental roots in ageing or synergistic diseases linked by vicious pathophysiological cycles remains unclear Insulin resistance is a core feature of T2DM and is emerging as a potentially important feature of ADRDs Here, we review key observations and experimental data on insulin signalling in the brain, highlighting its actions in neurons and glia In addition, we define the concept of 'brain insulin resistance' and review the growing, although still inconsistent, literature concerning cognitive impairment and neuropathological abnormalities in T2DM, obesity and insulin resistance Lastly, we review evidence of intrinsic brain insulin resistance in ADRDs By expanding our understanding of the overlapping mechanisms of these conditions, we hope to accelerate the rational development of preventive, disease-modifying and symptomatic treatments for cognitive dysfunction in T2DM and ADRDs alike

Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums

National Institute of Neurological Disorders and Stroke

Background Elevated blood pressure (BP) is common among patients presenting with acute ischemic stroke due to large vessel occlusions. The literature is inconsistent regarding the association between admission BP and outcome of mechanical thrombectomy (MT). Moreover, it is unclear whether the first line thrombectomy strategy (stent retriever [SR] versus contact aspiration [CA]) modifies the relationship between BP and outcome. Methods This is a post hoc analysis of the ASTER (Contact Aspiration Versus Stent Retriever for Successful Revascularization) randomized trial. BP was measured prior to randomization in all included patients. Co-primary outcomes included 90-day functional independence (modified Rankin Scale [mRS] 0-2) and successful revascularization (modified Treatment in Cerebral Ischemia [mTICI] 2b-3). Secondary outcomes included symptomatic intracerebral hemorrhage (sICH) and parenchymal hemorrhage (PH) within 24 hours. Results A total of 381 patients were included in the present study. Mean (SD) systolic BP (SBP) and diastolic BP (DBP) were 148 (26) mm Hg and 81 (16) mm Hg, respectively. There was no association between SBP or DBP and successful revascularization or 90-day functional independence. Similarly, there was no association between admission SBP or DBP with sICH or PH. Subgroup analysis based on the first-line thrombectomy strategy revealed similar results with no heterogeneity across groups. Conclusion Admission BP was not associated with functional, angiographic or safety outcomes. Results were similar in both CA and CA groups.

Admission Blood Pressure and Outcome of Endovascular Therapy: Secondary Analysis of ASTER Trial.

A 35-year-old man presented with one month history of vomitus, dizziness and headache. CT and MR imaging revealed a 3.5 x 3.2 cm solitary extra-axial midline mass arising from the frontal falx cerebri; radiological findings were diagnostic of meningioma of the falx. At surgery, the tumour appeared as an extra-axial lesion and was removed via a left midline frontal craniotomy. Macroscopically, the surgical specimen was whitish, soft, well circumscribed and measured 1.6 cm in diameter; microscopic features showed a neoplasm with high cellularity, presence of mitotic figures, without necrosis or microvascular proliferation; the neoplasm was reactive for glial fibrillary acidic protein and MIB-1 index was about 15%. Given the localization, microscopic features were diagnostic of primary intracranial solitary leptomeningeal astrocytoma (PLA), WHO grade 3. PLA is a very rare lesion that arises in the leptomeninges of the brain or spinal cord with no involvement of intraparenchymatous tissue. Fifteen cases of PLA are reported in the literature. Retrospective neuroradiological analysis of this case failed to detect any findings to help in the differential diagnosis, thus confirming the fundamental role of the neuropathologist even in what can firstly appear to be a straightforward radiological diagnosis.

35 year-old man with falcine tumor.

Spinal biopsies are carried out to obtain specimens of vertebral bodies or vertebral lesions. This provides biological samples for cytological and histopathological analyses. Primary and secondary tumors and infectious diseases are the most common causes for which vertebral biopses are required.

How and When to Carry Out Spinal Biopsy

Spinal cord arterio-venous shunts: From classification to therapeutic management

Resume Les endocardites infectieuses sont responsables de complications neurologiques non seulement sur le plan ischemique, mais elles peuvent determiner des meningites, des abces cerebraux et la formation d’anevrismes «mycotiques», qui sont detectes dans le 5 % des patients dans la phase aigue et sub-aigue de l’infection. Les donnees relatives et a l’histoire naturelle et au risque de saignement sont fragmentees et peu contributives. Les modalites therapeutiques sont representees par les traitements medicamenteux de l’infection avec une attitude conservatrice sur le plan interventionnel, le traitement chirurgical et le traitement endovasculaire par embolisation sans une evidence de superiorite d’une de ces options therapeutiques. Les anevrismes mycotiques restent un defi diagnostique et therapeutique et leur prise necessite d’une discussion multidisciplinaire.

Arturo Consoli

Papers

Admission Blood Pressure and Outcome of Endovascular Therapy: Secondary Analysis of ASTER Trial.

35 year-old man with falcine tumor.

How and When to Carry Out Spinal Biopsy

Spinal cord arterio-venous shunts: From classification to therapeutic management

Traitement interventionnel des anévrismes mycotiques cérébraux