Cerebral ischemic and hemorrhagic complications of coronavirus disease 2019.

BACKGROUND: The coronavirus disease 2019 is associated with neurological manifestations including stroke. OBJECTIVES: We present a case series of coronavirus disease 2019 patients from two institutions with acute cerebrovascular pathologies. In addition, we present a pooled analysis of published data on large vessel occlusion in the setting of coronavirus disease 2019 and a concise summary of the pathophysiology of acute cerebrovascular disease in the setting of coronavirus disease 2019. METHODS: A retrospective study across two institutions was conducted between 20 March 2020 and 20 May 2020, for patients developing acute cerebrovascular disease and diagnosed with coronavirus disease 2019. We performed a literature review using the PubMed search engine. RESULTS: The total sample size was 22 patients. The mean age was 59.5 years, and 12 patients were female. The cerebrovascular pathologies were 17 cases of acute ischemic stroke, 3 cases of aneurysm rupture, and 2 cases of sinus thrombosis. Of the stroke and sinus thrombosis patients, the mean National Institute of Health Stroke Scale was 13.8 ± 8.0, and 16 (84.2%) patients underwent a mechanical thrombectomy procedure. A favorable thrombolysis in cerebral infarction score was achieved in all patients. Of the 16 patients that underwent a mechanical thrombectomy, the mortality incidence was five (31.3%). Of all patients (22), three (13.6%) patients developed hemorrhagic conversion requiring decompressive surgery. Eleven (50%) patients had a poor functional status (modified Rankin Score 3-6) at discharge, and the total mortality incidence was eight (36.4%). CONCLUSIONS: Despite timely intervention and favorable reperfusion, the mortality rate in coronavirus disease 2019 patients with large vessel occlusion was high in our series and in the pooled analysis. Notable features were younger age group, involvement of both the arterial and venous vasculature, multivessel involvement, and complicated procedures due to the clot consistency and burden.

Severe Japanese encephalitis with multiple intracranial hemorrhages: A case report.

RATIONALE: Intracranial hemorrhage occurs infrequently in Japanese encephalitis (JE), and even less frequently with hemorrhage occurring twice. In this report, we describe the clinical features and outcomes of a patient with confirmed JE combined with hemorrhage twice. PATIENT CONCERNS: The patient, a 71-year-old Asian woman, was admitted to the hospital with symptoms of hemiplegia following fever and diarrhea. Soon her condition worsened and a decreased level of consciousness, respiratory failure, and paralysis of extremities occurred.The brain diffusion-weighted imaging sequence showed suspicious abnormal signals in bilateral thalami. Japanese encephalitis virus immunoglobulin M antibody was detected in her serum and cerebrospinal fluid samples, so the patient was diagnosed with JE. During treatment, her condition became aggravated and the brain computed tomography (CT) scan showed multiple lobar hemorrhages. One month later, the multiple lobar hemorrhages occurred again, as observed by a brain CT scan. DIAGNOSIS: JE with multiple intracranial hemorrhages. INTERVENTIONS: The patient was treated comprehensively, including surgery, lowering her intracranial pressure and ventilator-assisted breathing. OUTCOMES: One month later, the patient underwent another surgical procedure for intracranial hemorrhage and suffered a serious neurological disorder. LESSONS: Severe intracranial hemorrhage may occur in elderly patients with JE, especially in those with poor vascular condition. Therefore, when treating such patients, great caution, as well as early detection and prevention, should be taken in case of the occurrence of severe intracranial hemorrhage.

Varicella-zoster virus vasculopathy. A review description of a new case with multifocal brain hemorrhage.

BACKGROUND: The varicella zoster virus (VZV) is a highly neurotropic virus that, after the primary infection, remains latent in the nerve cells and can reactivate many years later, resulting in various conditions affecting the central nervous system, such as vasculopathy and stroke. METHODS: We report on a review of the published literature that included all case reports identified via PubMed and an additional unpublished case of VZV vasculopathy. All epidemiological, clinical, laboratory, imaging, virologic, treatment and outcome data collected are described. RESULTS: Of the 62 patients, 41.6% were immunocompromised. Ischemic stroke occurred in 77.2% of the patients, comprising cases of isolated (37.1%) and multifocal stroke (17.7%). Multifocal, ischemic and hemorrhagic stroke was only described in the newly reported case. The magnetic resonance imaging results were normal in 2.9% of the cases. The vascular studies (angiography and magnetic resonance angiography [MRA]) revealed signs of angiitis in 74.4% of the cases; the small arteries were involved in 38.5% of the cases, large arteries in 17.7% and mixed in 43.5%. For 95.2% of the patients, the cerebrospinal fluid (CSF) was positive for VZV IgG antibodies, and for 46.1% of the patients, the CSF was positive for polymerase chain reaction (PCR); however, the diagnosis was confirmed in only 3 of 6 biopsies. DISCUSSION: VZV vasculopathy can occur in both immunocompetent and immunosuppressed patients. Neuroimaging can reveal stroke and angiitis, and the detection of VZV-specific IgG antibodies in the CSF is a reliable and highly sensitive diagnostic tool. The multifocal nature of VZV vasculopathy makes biopsy a test with low sensitivity and high morbidity.

A hematopoietic contribution to microhemorrhage formation during antiviral CD8 T cell-initiated blood-brain barrier disruption.

BACKGROUND: The extent to which susceptibility to brain hemorrhage is derived from blood-derived factors or stromal tissue remains largely unknown. We have developed an inducible model of CD8 T cell-initiated blood-brain barrier (BBB) disruption using a variation of the Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis. This peptide-induced fatal syndrome (PIFS) model results in severe central nervous system (CNS) vascular permeability and death in the C57BL/6 mouse strain, but not in the 129 SvIm mouse strain, despite the two strains' having indistinguishable CD8 T-cell responses. Therefore, we hypothesize that hematopoietic factors contribute to susceptibility to brain hemorrhage, CNS vascular permeability and death following induction of PIFS. METHODS: PIFS was induced by intravenous injection of VP2121-130 peptide at 7 days post-TMEV infection. We then investigated brain inflammation, astrocyte activation, vascular permeability, functional deficit and microhemorrhage formation using T2*-weighted magnetic resonance imaging (MRI) in C57BL/6 and 129 SvIm mice. To investigate the contribution of hematopoietic cells in this model, hemorrhage-resistant 129 SvIm mice were reconstituted with C57BL/6 or autologous 129 SvIm bone marrow. Gadolinium-enhanced, T1-weighted MRI was used to visualize the extent of CNS vascular permeability after bone marrow transfer. RESULTS: C57BL/6 and 129 SvIm mice had similar inflammation in the CNS during acute infection. After administration of VP2121-130 peptide, however, C57BL/6 mice had increased astrocyte activation, CNS vascular permeability, microhemorrhage formation and functional deficits compared to 129 SvIm mice. The 129 SvIm mice reconstituted with C57BL/6 but not autologous bone marrow had increased microhemorrhage formation as measured by T2*-weighted MRI, exhibited a profound increase in CNS vascular permeability as measured by three-dimensional volumetric analysis of gadolinium-enhanced, T1-weighted MRI, and became moribund in this model system. CONCLUSION: C57BL/6 mice are highly susceptible to microhemorrhage formation, severe CNS vascular permeability and morbidity compared to the 129 SvIm mouse. This susceptibility is transferable with the bone marrow compartment, demonstrating that hematopoietic factors are responsible for the onset of brain microhemorrhage and vascular permeability in immune-mediated fatal BBB disruption.

Hemorrhagic encephalitis associated with Epstein-Barr virus infection.

Epstein-Barr virus (EBV) encephalitis is a rare neurological complication, usually only reported in pediatric patients. We present a 20-year-old, previously healthy male who developed hemorrhagic encephalitis caused by EBV. He was admitted to our hospital with a 1-week history of fever, diarrhea, headache, and confusion. Brain T2-weighted MRI showed a focal area of increased signal in the right temporal lobe. Brain MRI and CT scans on day 2 revealed progression of the lesion, with partial hemorrhagic change, acute brain swelling, and severe midline shift. The patient underwent external decompression and external ventricular drainage. EBV DNA was identified in brain biopsy specimens by polymerase chain reaction. The postoperative course was uneventful. To our knowledge, this is the second report of hemorrhagic EBV encephalitis in an adult.

Pathology of goose haemorrhagic polyomavirus infection in goose embryos.

Goose embryos were infected with goose haemorrhagic polyomavirus (GHPV) onto the chorioallantoic membrane (CAM) in order to examine the effect of GHPV on the embryos and to obtain data on whether embryos could develop into infected, virus-shedding goslings, as well as to present an accurate biological method for virus titration. The reported method of infection could offer a possibility to express the virus titre as the median embryo infective dose (EID(50)). As a special pathological feature of the disease, extensive cerebral haemorrhages were observed, which protruded the skullcap in many cases. Some embryos infected with 10(1.25) or 10(0.25) EID(50)/0.2 ml were able to hatch; however, they were in poor physical condition and died by post-hatching day 4 showing haemorrhagic nephritis and enteritis of geese. Virus shedding was revealed by polymerase chain reaction. The ability of some of the infected goose embryos to hatch may indicate the potency of GHPV to spread vertically, although this needs further study for confirmation.

Management of coagulopathy with recombinant factor VIIa in a neonate with echovirus type 7.

A 5-day-old newborn presented with neonatal enteroviral infection. The patient's hospital course was complicated by acute liver dysfunction, renal insufficiency, fluid overload, respiratory failure, hypertension, catheter related thrombosis, Klebsiella pneumoniae sepsis, intracerebral and intraventricular hemorrhage, and disseminated intravascular coagulation (DIC). Administration of fresh frozen plasma (FFP) and cryoprecipitate failed to control the patient's hemostasis and led to significant fluid overload. Recombinant activated factor VII (rFVIIa, Novoseven NovoNordisk, Bagsvaerd, Denmark) was given to the neonate as a bolus (rFVIIa at 60-80 microg/kg body weight), followed by a continuous infusion (2.5-16 microg/kg/hr). Recombinant activated factor VII controlled hemostasis, until the patient's liver function recovered. The patient's blood product requirement significantly decreased and his fluid overload resolved. Administration of rFVIIa appears to have stabilized the coagulation process. The patient appears to have fully recovered from the infection's complications.