Small vessel childhood primary angiitis of the central nervous system with positive anti-glial fibrillary acidic protein antibodies: a case report and review of literature.

BACKGROUND: Small vessel childhood primary angiitis of the central nervous system (SV-cPACNS) is a rare disease characterized by inflammation within small vessels such as arterioles or capillaries. CASE PRESENTATION: We report a case of SV-cPACNS in an 8-year-old boy confirmed by brain biopsy. This patient was also incidentally found to have anti-glial fibrillary acidic protein (GFAP) antibodies in the cerebrospinal fluid (CSF) but had no evidence of antibody-mediated disease on brain biopsy. A literature review highlighted the rarity of SV-cPACNS and found no prior reports of CSF GFAP-associated SV-cPACNS in the pediatric age group. CONCLUSION: We present the first case of biopsy proven SV-cPACNS vasculitis associated with an incidental finding of CSF GFAP antibodies. The GFAP antibodies are likely a clinically insignificant bystander in this case and possibly in other diseases with CNS inflammation. Further research is needed to determine the clinical significance of newer CSF autoantibodies such as anti-GFAP before they are used for medical decision-making in pediatrics.

Evolution of Neuroimaging Findings in Severe COVID-19 Patients with Initial Neurological Impairment: An Observational Study.

BACKGROUND AND OBJECTIVES: Cerebral complications related to the COVID-19 were documented by brain MRIs during the acute phase. The purpose of the present study was to describe the evolution of these neuroimaging findings (MRI and FDG-PET/CT) and describe the neurocognitive outcomes of these patients. METHODS: During the first wave of the COVID-19 outbreak between 1 March and 31 May 2020, 112 consecutive COVID-19 patients with neurologic manifestations underwent a brain MRI at Strasbourg University hospitals. After recovery, during follow-up, of these 112 patients, 31 (initially hospitalized in intensive care units) underwent additional imaging studies (at least one brain MRI). RESULTS: Twenty-three men (74%) and eight women (26%) with a mean age of 61 years (range: 18-79) were included. Leptomeningeal enhancement, diffuse brain microhemorrhages, acute ischemic strokes, suspicion of cerebral vasculitis, and acute inflammatory demyelinating lesions were described on the initial brain MRIs. During follow-up, the evolution of the leptomeningeal enhancement was discordant, and the cerebral microhemorrhages were stable. We observed normalization of the vessel walls in all patients suspected of cerebral vasculitis. Four patients (13%) demonstrated new complications during follow-up (ischemic strokes, hypoglossal neuritis, marked increase in the white matter FLAIR hyperintensities with presumed vascular origin, and one suspected case of cerebral vasculitis). Concerning the grey matter volumetry, we observed a loss of volume of 3.2% during an average period of approximately five months. During follow-up, the more frequent FDG-PET/CT findings were hypometabolism in temporal and insular regions. CONCLUSION: A minority of initially severe COVID-19 patients demonstrated new complications on their brain MRIs during follow-up after recovery.

Lethal Pediatric Cerebral Vasculitis Triggered by Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: We report the clinical, radiological, laboratory, and neuropathological findings in support of the first diagnosis of lethal, small-vessel cerebral vasculitis triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric patient. PATIENT DESCRIPTION: A previously healthy, eight-year-old Hispanic girl presented with subacute left-sided weakness two weeks after a mild febrile illness. SARS-CoV-2 nasopharyngeal swab was positive. Magnetic resonance imaging revealed an enhancing right frontal lobe lesion with significant vasogenic edema. Two brain biopsies of the lesion showed perivascular and intraluminal lymphohistiocytic inflammatory infiltrate consistent with vasculitis. Despite extensive treatment with immunomodulatory therapies targeting primary angiitis of the central nervous system, she experienced neurological decline and died 93 days after presentation. SARS-CoV-2 testing revealed positive serum IgG and positive cerebrospinal fluid IgM. Comprehensive infectious, rheumatologic, hematologic/oncologic, and genetic evaluation did not identify an alternative etiology. Postmortem brain autopsy remained consistent with vasculitis. CONCLUSION: This is the first pediatric presentation to suggest that SARS-CoV-2 can lead to a fatal, postinfectious, inflammatory small-vessel cerebral vasculitis. Our patient uniquely included supportive cerebrospinal fluid and postmortem tissue analysis. While most children recover from the neurological complications of SARS-CoV-2, we emphasize the potential mortality in a child with no risk factors for severe disease.

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.

Cerebral vasculitis of medium-sized vessels as a possible mechanism of brain damage in COVID-19 patients.

BACKGROUND AND PURPOSE: Cerebral complications related to COVID-19 were recently reported, and the underlying mechanisms of brain damage remain uncertain, probably multifactorial. Among various hypotheses suggested, a possible vasculitis was issued but never confirmed. Herein, we aimed to describe brain MRIs focused on the intracranial vessel wall in a population of COVID-19 patients with neurologic manifestations. MATERIALS AND METHODS: Between March 1 and May 31, 2020, 69 consecutive COVID-19 patients with neurologic manifestations underwent a brain MRI allowing the study of the intracranial vessel wall at Strasbourg University hospitals and were retrospectively included. During the same period, 25 consecutive patients, without suspicion of SARS-CoV-2 infection, underwent a brain MRI urgently, with the same imaging protocols. A vasculitis seemed likely when imaging demonstrated vessel wall thickening with homogeneous and concentric enhancement. RESULTS: Among the 69 COVID-19 patients included, 11 (16%) presented arterial vessel wall thickening with homogeneous and concentric enhancement, compatible with cerebral vasculitis. These neuroimaging findings were not found among the 25 patients without SARS-CoV-2 infection, and the difference was statistically significant (p = 0.03). Middle cerebral arteries, basilar artery, and posterior cerebral arteries were the most frequent vessels involved. For nine of them, imaging demonstrated ischemic or hemorrhagic complications. CONCLUSION: Cerebral vasculitis of medium-sized vessels seems to be one of the mechanisms at the origin of brain damage related to COVID-19.

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.

Cerebral nervous system vasculitis in a Covid-19 patient with pneumonia.

We describe a patient affected by Covid-19 acute respiratory distress syndrome with a cerebral nervous system vasculitis triggered by SARS-Cov-2, managed at the University hospital, in Novara, Italy in the area most impacted by the pandemic and where 749 Covid-19 positive patients were admitted from March 1st until April 25th, 2020.

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.

COVID-19 Neurologic Complication with CNS Vasculitis-Like Pattern.

Coronavirus disease 2019 (COVID-19) is a viral infection caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), which spreads rapidly from person to person and manifests in most symptomatic patients as a respiratory illness, similar to prior SARS viruses. Neurologic manifestations of COVID-19 are uncommon; those so far reported include encephalopathy, stroke from large-vessel occlusion, and polyneuropathy. We report a unique neurologic complication of COVID-19 in a patient who had extensive cerebral small-vessel ischemic lesions resembling cerebral vasculitis in a characteristic combined imaging pattern of ischemia, hemorrhage, and punctuate postcontrast enhancement. Also, a characteristic lower extremity skin rash was present in our patient. Our observation lends support to the increasingly suspected mechanism of "endotheliitis" associated with this novel coronavirus.

UK-Wide Surveillance of Neurological and Neuropsychiatric Complications of COVID-19: The First 153 Patients (preprint)

Background: Increasingly neurological complications of COVID-19 are identified, mostly in small series. Larger studies have been limited by both geography and specialty.Consequently, the breadth of complications is not represented. Comprehensive characterization of clinical syndromes is critical to rationally select and evaluate potential therapies.Methods: During the exponential pandemic phase, we developed coordinated online portals for rapid notification across the spectrum of major UK neuroscience bodies, representing neurology, stroke, psychiatry, and intensive care. Evidence of infection and clinical case definitions were applied prospectively. Cases were compared to overall Government Public Health COVID-19 reporting.Findings: Within three weeks, 153 cases were notified, both geographically and temporally representative of overall COVID-19 Public Health reports. Median (range) age was 71 (23-94) years. 77 (62%) had a cerebrovascular event: 57 (74%) ischemic strokes, nine (12%) intracerebral hemorrhages, and one CNS vasculitis.The second most common group were 39 (31%) who had altered mental status, including 16 (41%) with encephalopathy of whom seven (44%) had encephalitis. The remaining 23 (59%) had a psychiatric diagnosis of whom 21 (92%) were new diagnoses; including ten (43%) with psychosis, six (26%) neurocognitive (dementia-like) syndrome, and 4 (17%) an affective disorder. Cerebrovascular events predominated in older patients. Conversely, altered mental status, whilst present in all ages, had disproportionate representation in the young.Interpretation: This is the first nationwide, cross-specialty surveillance study of acute complications of COVID-19 in the nervous system. Alteration in mental status was common, reflecting encephalopathy/encephalitis and primary psychiatric diagnoses, often in young patients.These data provide valuable and timely information urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy throughout the areas of neurology and neuropsychiatry.