COVID-19 leukoencephalopathy with subacute magnetic resonance imaging findings of vasculitis and demyelination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) commonly results in a respiratory illness in symptomatic patients; however, those critically ill can develop a leukoencephalopathy. We describe two patients who had novel subacute MRI findings in the context of coronavirus disease 2019 (COVID-19) leukoencephalopathy, which we hypothesize could implicate a potent small-vessel vasculitis, ischemic demyelination and the presence of prolonged ischemia. Recent evidence of the direct neuroinvasiness of SARS-CoV-2 leading to ischemia and vascular damage supports this hypothesis.

Intracerebral endotheliitis and microbleeds are neuropathological features of COVID-19.

Coronavirus disease 19 (COVID-19) is a rapidly evolving pandemic caused by the coronavirus Sars-CoV-2. Clinically manifest central nervous system symptoms have been described in COVID-19 patients and could be the consequence of commonly associated vascular pathology, but the detailed neuropathological sequelae remain largely unknown. A total of six cases, all positive for Sars-CoV-2, showed evidence of cerebral petechial hemorrhages and microthrombi at autopsy. Two out of six patients showed an elevated risk for disseminated intravascular coagulopathy according to current criteria and were excluded from further analysis. In the remaining four patients, the hemorrhages were most prominent at the grey and white matter junction of the neocortex, but were also found in the brainstem, deep grey matter structures and cerebellum. Two patients showed vascular intramural inflammatory infiltrates, consistent with Sars-CoV-2-associated endotheliitis, which was associated by elevated levels of the Sars-CoV-2 receptor ACE2 in the brain vasculature. Distribution and morphology of patchy brain microbleeds was clearly distinct from hypertension-related hemorrhage, critical illness-associated microbleeds and cerebral amyloid angiopathy, which was ruled out by immunohistochemistry. Cerebral microhemorrhages in COVID-19 patients could be a consequence of Sars- CoV-2-induced endotheliitis and more general vasculopathic changes and may correlate with an increased risk of vascular encephalopathy.

[Multiple cerebral hemorrhages due to varicella-zoster virus vasculopathy presenting as cranial nerve palsy].

A 72-year-old man was admitted to our hospital because of right facial muscle weakness and diplopia. He had been treated for aplastic anemia with cyclosporin for 2 years. Thirteen days before admission, a diagnosis of herpes zoster was made and treated with amenamevir. On admission, neurological examination revealed mild cognitive disturbance, mydriasis, weakness of the inferior rectus muscle of the left eye, and right peripheral facial nerve palsy. Cerebrospinal fluid (CSF) analysis showed elevated leukocytes and increased protein levels. Antibody index to varicella-zoster virus (VZV) was elevated in CSF to 25.6, although VZV DNA was negative by PCR. Head CT revealed multiple intracerebral hemorrhages in the left dorsal pons, left ventral midbrain, left thalamus, and left front-parietal lobe. MR angiography detected cerebral artery stenosis. In addition to intravenous acyclovir, the patient was treated with steroid pulse therapy and steroid tapering therapy. One month after admission, his symptoms improved. We diagnosed him with VZV vasculopathy. We believe that multiple intracerebral hemorrhages due to VZV vasculopathy caused facial and oculomotor nerve palsy. Our findings suggest that cerebral hemorrhage induced by VZV vasculopathy must be considered when differentiating cranial nerve palsy after herpes zoster.

Transplacental transmission of SARS-CoV-2 infection.

SARS-CoV-2 outbreak is the first pandemic of the century. SARS-CoV-2 infection is transmitted through droplets; other transmission routes are hypothesized but not confirmed. So far, it is unclear whether and how SARS-CoV-2 can be transmitted from the mother to the fetus. We demonstrate the transplacental transmission of SARS-CoV-2 in a neonate born to a mother infected in the last trimester and presenting with neurological compromise. The transmission is confirmed by comprehensive virological and pathological investigations. In detail, SARS-CoV-2 causes: (1) maternal viremia, (2) placental infection demonstrated by immunohistochemistry and very high viral load; placental inflammation, as shown by histological examination and immunohistochemistry, and (3) neonatal viremia following placental infection. The neonate is studied clinically, through imaging, and followed up. The neonate presented with neurological manifestations, similar to those described in adult patients.

Influenza-Induced Acute Macular Neuroretinopathy With Cerebral Involvement in a Ten-Year-Old Boy.

A 10-year-old male presented with 1-week duration of painless bilateral central vision loss after having been diagnosed with influenza A. Optical coherence tomography revealed superficial retinal nerve fiber layer infarcts, hyperreflectivity of the inner nuclear layer consistent with paracentral acute middle maculopathy (PAMM), and outer nuclear layer hyperreflectivity and disruption of the ellipsoid zone suggesting acute macular neuroretinopathy (AMN). Brain MRI revealed enhancement of the right basal ganglia consistent with focal encephalitis. He was diagnosed with presumed influenza-induced leukocytoclastic vasculitis (LCV) and treated with intravenous steroids. Influenza-induced LCV is a rare phenomenon and can present with AMN, PAMM, and encephalitis. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:293-297.].

Recurrent strokes, central nervous system vasculitis, and acquired protein S deficiency secondary to varicella zoster in a child with AIDS.

A child with vertical transmission of human immunodeficiency virus refractory to therapy developed zoster-induced protein S deficiency and recurrent strokes. Extensive carotid arteritis was found postmortem. The carotid tissue was positive for herpes varicella zoster by polymerase chain reaction, as were immunofixation stains of the arterial wall.

[Rapidly deteriorated lobar intracerebral hemorrhages: possible association of varicella zoster virus-vasculopathy].

A 75-year-old man having dementia and lifestyle related diseases developed a lobar intracerebral hemorrhage (LICH) in the left parietal and a small cerebellar infarction in the left occipital lobe. Many micro bleeds (MB) due to cerebral amyloid angiopathy (CAA) in the subcortical areas and multiple vascular stenosis were also found by MRI and MRA. He developed herpes zoster in his buttocks on day 6 of hospitalization and complicated with varicella zoster virus (VZV) meningitis with positive for VZV-DNA in the cerebrospinal fluid. Subsequently, LICHs occurred in the left frontal lobe and in the right parietal lobe for a short period of time and died on the day 18. We speculated that the repeating hemorrhages was primarily caused by VZV vasculopathy and additionally the subcortical MBs increased the hemorrhagic risk. The relationship between VZV vasculopathy and CAA should be studied in the future.

Magnetic resonance imaging in central nervous system vasculitis in a patient affected by crioglobulin-negative hepatitis C virus infection: A likely correlation.

A 56-year-old man with behavioural disorders and facial-brachio-crural right hemiparesis presented with a brain lesion studied with computed tomography, magnetic resonance imaging and brain biopsy, leading to the diagnosis of cerebral vasculitis. Hepatitis C virus (HCV) infection in a phase of activity, without cryoglobulins, was also detected. Brain biopsy, laboratory analysis and response to a specific therapy supported the diagnosis of central nervous system vasculitis that was HCV related.

Case report of a 28-year-old male with the rapid progression of steroid-resistant central nervous system vasculitis diagnosed by a brain biopsy.

A 28-year-old Japanese male without a significant past medical history presented with new-onset generalized clonic seizure and headache. A brain MRI revealed multiple enhanced lesions on both cerebral hemispheres. Laboratory exams showed no evidence of systemic inflammation or auto-immune antibodies such as ANCAs. Despite four courses of high-dose methylprednisolone pulse therapy and five treatments with plasmapheresis, his symptoms worsened and the MRI lesions progressed rapidly. During these treatments, we performed a targeted brain biopsy, that revealed histological findings consistent with a predominant angiitis of parenchymal and subdural small vessels. He was provided with diagnosis of central nervous system vasculitis (CNSV). Subsequent cyclophosphamide pulse therapy enabled a progressive successful improvement of his symptoms. While diagnostic methods for CNSV remain controversial, histological findings are thought to be more useful in obtaining a more definitive diagnosis than findings in image studies, such as MRI and angiography. We suggest that a brain biopsy should be considered during the early period of cases with suspected CNSV and rapid clinical deterioration. We also detected human herpesvirus 7 (HHV-7) using PCR technology in brain biopsy specimens, however the relationship between CNSV and HHV-7 infection is unknow.

High-Resolution Vessel Wall Magnetic Resonance Imaging in Varicella-Zoster Virus Vasculitis.

Varicella-zoster virus vasculopathy is a rare but potentially treatable condition. Diagnosis has been based on angiography, brain magnetic resonance imaging (MRI), and cerebrospinal fluid analysis. High-resolution vessel wall MRI may aid to the diagnosis by differentiating inflammation from other vessel wall pathologies. We present the characteristic MRI findings of this condition in a young patient presenting with ischemic stroke.

Varicella Zoster Virus Infection in Granulomatous Arteritis of the Aorta.

Granulomatous arteritis characterizes the pathology of giant cell arteritis, granulomatous aortitis, and intracerebral varicella zoster virus (VZV) vasculopathy. Because intracerebral VZV vasculopathy and giant cell arteritis are strongly associated with productive VZV infection in cerebral and temporal arteries, respectively, we evaluated human aortas for VZV antigen and VZV DNA. Using 3 different anti-VZV antibodies, we identified VZV antigen in 11 of 11 aortas with pathologically verified granulomatous arteritis, in 1 of 1 cases of nongranulomatous arteritis, and in 5 of 18 control aortas (28%) obtained at autopsy. The presence of VZV antigen in granulomatous aortitis was highly significant (P = .0001) as compared to control aortas, in which VZV antigen was never associated with pathology, indicating subclinical reactivation. VZV DNA was found in most aortas containing VZV antigen. The frequent clinical, radiological, and pathological aortic involvement in patients with giant cell arteritis correlates with the significant detection of VZV in granulomatous aortitis.

[Varicella zoster meningitis with associated vasculitis in a two-month post-partum woman]. / Varicella zoster-meningitis med associeretvaskulitis hos en nybagt mor

Reactivation of varicella zoster virus occurs more often in the elderly or immunocompromised persons. During pregnancy increased anti-inflammatory cellular response promotes tolerance of foetal antigens. Post-partum a shift towards an inflammatory response may facilitate the reoccurrence of latent infections. Varicella-associated vasculitis can lead to ischaemic lesions in the brain. We report a case of a two-month post-partum woman suffering from headache, nausea, vomiting, photophobia and radicular pain with varicella zoster meningitis and an ischaemic lesion in the splenium of corpus callosum.

Síndrome da angústia respiratória aguda associada à varicela em paciente adulto: exemplo de suporte respiratório extracorpóreo em doenças endêmicas brasileiras / Varicella associated acute respiratory distress syndrome in an adult patient: an example for extracorporeal respiratory support in Brazilian endemic diseases

Descreveu-se aqui o caso de um homem de 30 anos de idade com quadro de varicela grave, hipoxemia refratária, vasculite do sistema nervoso central e insuficiência renal anúrica. Foi necessário transporte por ambulância com suporte respiratório extracorpóreo veno-venoso, sendo este utilizado até a recuperação do paciente. Discute-se o potencial uso de oxigenação por membrana extracorpórea em países em desenvolvimento para o controle de doenças comuns nestas áreas.

A case of a 30 year-old man presenting with severe systemic chickenpox with refractory hypoxemia, central nervous system vasculitis and anuric renal failure is described. Ambulance transportation and support using veno-venous extracorporeal membrane oxygenation were necessary until the patient recovered. Ultimately, the potential use of extracorporeal membrane oxygenation support in low-middle income countries to manage common diseases is discussed.

Cerebral vasculitis and encephalitis due to Epstein-Barr virus in a patient with newly diagnosed HIV infection.

Epstein-Barr virus (EBV) is a common infection which usually produces mild or no symptoms in immunocompetent individuals. In human immunodeficiency virus (HIV) associated immunosuppression it is most commonly associated with malignancy which usually occurs at very low CD4+ cell counts. We describe a newly diagnosed HIV-positive patient who presented with headaches and cerebellar signs. She was incorrectly diagnosed with cerebral tuberculosis (TB) infection based on the histology report from a cerebellar biopsy specimen. After extensive investigation including cerebrospinal fluid sampling and reanalysis of the brain biopsy specimens she was found to have EBV-associated cerebral vasculitis and encephalitis and was successfully treated with valganciclovir and steroids. Whilst there are a few reports of EBV-associated encephalitis, cerebral vasculitis secondary to EBV in the context of HIV infection has not previously been described in the literature.

Central nervous system-immune reconstitution inflammatory syndrome presenting as varicella zoster virus-mediated vasculitis causing stroke.

Varicella zoster virus (VZV)-mediated vasculitis is a rare cause of stroke, but should be considered in HIV patients where vasculitis can occur in association with central nervous system - immune reconstitution inflammatory syndrome (CNS-IRIS). A literature search revealed 7 reports of VZV vasculitis over the years with no unifying management strategy, highlighting the difficulty in managing rare conditions in the absence of clear guidelines. This is the first documented case of VZV-mediated vasculitis presenting as stroke in the United Kingdom. Our patient made a full recovery with multidisciplinary input from HIV, neurology and radiology specialists.

Varicella associated acute respiratory distress syndrome in an adult patient: an example for extracorporeal respiratory support in Brazilian endemic diseases.

A case of a 30 year-old man presenting with severe systemic chickenpox with refractory hypoxemia, central nervous system vasculitis and anuric renal failure is described. Ambulance transportation and support using veno-venous extracorporeal membrane oxygenation were necessary until the patient recovered. Ultimately, the potential use of extracorporeal membrane oxygenation support in low-middle income countries to manage common diseases is discussed.

Vessel wall enhancement in herpes simplex virus central nervous system vasculitis.

Infection is a well-known cause of cerebral vasculopathy and vasculitis. We report a 36-year-old woman with cerebral vasculitis and ischemic stroke secondary to herpes simplex virus (HSV). MRI studies revealed a pontine stroke with basilar artery stenosis and vessel wall gadolinium enhancement. This case demonstrates the ability of HSV to cause a focal brainstem vasculitis and the utility of enhanced MRI in the diagnosis of stroke related to HSV central nervous system vasculitis.