Relation between the Severity of the Sensorimotor Cortical Edema with Cell Swelling and the Duration of Common Carotid Artery Occlusion in Rats (Morphometric Study)

The aim of the study. To examine the changes in structure and morphometry in sensorimotor cortical edema with cell swelling in mature white rats after common carotid artery occlusion of various durations.Material and methods. Acute ischemia was modeled on white adult Wistar rats by 20-, 30- and 40-min occlusion of the common carotid arteries (CCA). Histological (hematoxylin-eosin and Nissl staining), immunohistochemical (NSE, MAP-2, GFAP) and morphometric methods were used. Morphometry was assessed on hematoxylin and eosin-stained specimens using ImageJ 1.53 plug-ins (Find Maxima, Find Foci). Statistical hypothesis testing (nonparametric criteria) was performed using Statistica 8.0 software.Results. In the sensorimotor cortex (SMC) of white rats after 20, 30 and 40 minutes of CCA occlusion the signs of cytotoxic brain edema appeared, focal destructive and adaptive changes of neurons and astroglia evolved. The edema persisted throughout the observation period (7 days). The increase in the relative area, the number of cell swelling zones and their hydration (pixel brightness) was significant. On days 1 and 3 after CCA occlusion, some of the SMC astrocyte processes underwent destruction. Subpial and perivascular zones suffered to a greater extent. Mild and moderate (after unilateral 30-min CCA occlusion) to moderate and severe (after bilateral 40-min CCA occlusion) scattered structural and functional changes of the SMC with large areas of clearing in the «porous» neuropil, severe perivascular and perineuronal edema of the astrocyte processes developed. The latter was associated with a moderate reduction of the total neuronal density.Conclusion. After occlusion of CCA, signs of edema with cellular swelling appeared in the SMC amid dystrophic and necrotic pyramidal neurons and activated neuroglial cells. To a greater extent, the signs of brain swelling were evident three days after bilateral 40-min occlusion of CCA.

Rate of Leptomeningeal Enhancement in Pediatric Myelin Oligodendrocyte Glycoprotein Antibody–Associated Encephalomyelitis

Introduction: Myelin oligodendrocyte glycoprotein antibodies (MOG-abs) are associated with demyelinating diseases. Leptomeningeal enhancement occurs in 6% of adult MOG-abs patients but rates in pediatric MOG-abs patients are unknown. Methods: Retrospective review of pediatric MOG-abs patients was performed. Results: Twenty-one patients (7 boys, 14 girls) were included with an average age of 8.6 years (range 2-15 years). Seven of 21 (33%) pediatric MOG-abs patients had leptomeningeal enhancement. Two patients’ relapses were manifested by leptomeningeal enhancement alone and another patient presented with seizures, encephalopathy, and aseptic meningitis without demyelinating lesions. Cerebrospinal fluid pleocytosis was seen in both leptomeningeal (4/7 patients) and nonleptomeningeal enhancement (10/14 patients). Interestingly, 3 patients with leptomeningeal enhancement had normal cerebrospinal fluid white blood cell count. Cortical edema was more likely in patients with leptomeningeal enhancement ( P = .0263). Conclusion: We expand the clinical spectrum of anti-MOG antibody–associated disorder. Patients with recurrent leptomeningeal enhancement without demyelinating lesions should be tested for MOG antibodies.

COVID-19 Thrombosis: Understanding the Negative Predictive Value in a Pandemic

A test's negative predictive value-the probability that a negative result is a true negative result-is dependent on the prevalence of the condition. The present pandemic circumstances present us with unique challenges. False negatives in current testing methodology are to be expected.[1] Thus, a rigorous and contextual interpretation of a negative test result is necessary. Blood hypercoagulability and the risk of thrombosis are well documented in cases of the novel SARS-CoV-2 coronavirus (COVID-19) pandemic.[2] The systemic inflammatory response is associated with endothelial upregulation of proinflammatory mediators that lead to in situ thrombi, as well as a generalized disseminated intravascular coagulation. As many as 31% of ICU patients with COVID-19 have been reported to have thrombotic complications. More specifically, cerebral thrombotic complications confined to the arterial bed have been well described.[3, 4]. The case described shows that milder forms of coronavirus infection may lead to other types of critical and unusual thrombotic complications. An otherwise healthy 47-year-old Caucasian woman developed fever and respiratory signs and symptoms consistent with a possible case of COVID-19 infection in late March of 2020. Interstitial opacities were seen on radiographic examination. Two COVID-19 PCR nasopharyngeal tests were negative, and she recovered at home over the following 2 weeks. Three weeks later, she developed headaches, expressive aphasia, and a generalized tonic-clonic seizure. The patient was treated for a possible ischemic stroke with alteplase thrombolysis at a local hospital. After subsequent transfer and evaluation, a diagnosis of a left transverse and sigmoid sinus thrombosis with adjacent cortical edema was made. On review of her history, the patient denied taking any form of hormonal contraception, and did not have personal, or family history indicative of thrombophilia. She recovered fully after anticoagulation with enoxaparin and subsequent dabigatran. Prior to discharge a COVID-19, IgG antibody test was reported as positive. Decontextualized and overly simplistic interpretation of COVID-19 negative tests amidst a pandemic is problematic. In addition to the obvious infection control issues associated with the resulting lack of isolation and contract tracing, it may deprive some patients of the opportunity to receive antithrombotic therapy. Prophylactic and therapeutic regimens for hospitalized patients are in evolution, and have been associated with improved clinical outcomes.[5] We are aware that the role of anticoagulation in outpatient cases is not well studied, but we believe it deserves proper investigation. References: West, C.P., V.M. Montori, and P. Sampathkumar,COVID-19 Testing: The Threat of False Negative Results.Mayo Clin Proc, 2020.Thachil, J., et al.,ISTH interim guidance on recognition and management of coagulopathy inCOVID-19.J Thromb Haemost, 2020.18(5): p. 1023-1026.Oxley, T.J., et al.,Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young.N Engl J Med, 2020.Klok, F.A., et al.,Confirmation of the high cumulative incidence of thrombotic complications incritically ill ICU patients with COVID-19: An updated analysis.Thromb Res, 2020.Paranjpe, I., et al.,Association of Treatment Dose Anticoagulation with In-Hospital SurvivalAmong Hospitalized Patients with COVID-19.J Am Coll Cardiol, 2020. Disclosures No relevant conflicts of interest to declare.

Hypertensive Encephalopathy in Children with Sickle Cell Disease.

Cerebrovascular (CVA) accidents are a serious complication of Sickle Cell Disease (SCD). Acute cerebral infarction occurs in approximately 10% of children with SCD under the age of 16 years, with silent infarcts identified in an additional 22%. Children however can present with acute neurologic deterioration mimicking a CVA but demonstrate a picture consistent with hypertensive encephalopathy (HTNE). The incidence of HTNE in children with SCD is unknown with few annedoctal reports available in the literature. We retrospectively identified 83 children with SCD, who received their care at Children’s National Medical Center in Washington, DC, from 1992 to 2005, who presented with neurologic complaints that prompted Magnetic Resonance Imaging (MRI). There were 37 females and 46 males, age 13 months to 17 years, with mean age of 5 years and 8 months. Clinical and neuro-imaging data identified 8 children (7 females and 1 male) with clinical picture compatible with HTNE (BP > 2 std deviation for age), prior to neuroimaging. At the time of the hypertensive episode, the ages ranged from 6 to 16 years and 8 months, with an average of 14 years and 2 months. All patients had Hb SS. Neurologic complaints included seizure, sudden onset headache, confusion, loss of consciousness, and urinary retention. Elevated blood pressures were aggressively treated and all patient received an exchange transfusion. No specific etiology for the hypertension was determined. Initial MRI, obtained within 24–48 hours of presentation, did not show acute or prior infarction in this group. However, there was absence of diffusion restriction on T1 and T2 weighted images, and presence of cerebral cortical edema, which differentiate HTNE from acute infarction. The magnetic resonance angiogram (MRA) did not demonstrate evidence of arteriopathy. The hallmark of HTNE is a complete resolution of abnormalities of both the neurologic exam and the imaging studies at follow up. There was complete resolution of cerebral edema in all patients and mild interval prominence of the cerebral sulci, which can indicate cerebral volume loss, in three out of the 8 patients, in follow up studies obtained 10 days to 4 months later. No recurrences of the symptoms have been reported, with follow up ranging from 5 months to 8 years. None of the patients with HTNE has received chronic transfusions. We conclude that HTNE should be considered in the differential diagnosis of an acute neurologic event in a child with SCD. Accurate recording of vital signs and prompt correction of hypertension is indicated. MRI can accurately distinguish between HTNE and acute infarction, even when clinical symptoms are similar. This distinction helps physicians to establish proper treatment such as chronic transfusion following infarction.