Comparison of nucleocapsid antigen with strand-specific reverse-transcription PCR for monitoring SARS-CoV-2 infection.

BACKGROUND: Tests that sensitively detect the presence of actively replicating SARS-CoV-2 may improve patient care by allowing the safe and timely discontinuation of isolation. Correlates of active replication include nucleocapsid antigen and virus minus-strand RNA. METHODS: Qualitative agreement of the DiaSorin LIAISON SARS-CoV-2 nucleocapsid antigen chemiluminescent immunoassay (CLIA) with minus-strand RNA was determined using 402 upper respiratory specimens from 323 patients previously tested using a laboratory-developed SARS-CoV-2 strand-specific RT-qPCR. Nucleocapsid antigen levels, minus-strand and plus-strand cycle threshold values, as well as virus culture, were used to evaluate discordant specimens. Receiver operating characteristic curves were also used to identify virus RNA thresholds for active replication, including values harmonized to the World Health Organization International Standard. RESULTS: Overall agreement was 92.0% [95% confidence interval (CI): 89.0 - 94.5], positive percent agreement was 90.6% (95% CI: 84.4 - 95.0), and negative percent agreement was 92.8% (95% CI: 89.0 - 95.6). The kappa coefficient was 0.83 (95% CI: 0.77 - 0.88). Discordant specimens contained low levels of nucleocapsid antigen and minus-strand RNA. 84.8% (28/33) were negative by culture. Sensitivity-optimized plus-strand RNA thresholds for active replication were 31.6 cycles or 3.64 log10 IU/mL; resulting in 100.0% sensitivity (95% CI: 97.6 to 100.0) and 55.9 specificity (95% CI: 49.7 to 62.0). CONCLUSIONS: Detection of nucleocapsid antigen by CLIA performs equivalently to minus-strand detection via strand-specific RT-qPCR, though these methods may overestimate replication-competent virus compared to culture. Careful implementation of biomarkers for actively replicating SARS-CoV-2 has the potential to inform infection control decision-making and patient management.

Large vessel stroke in six patients following SARS-CoV-2 infection: a retrospective case study series of acute thrombotic complications on stable underlying atherosclerotic disease.

BACKGROUND AND PURPOSE: Ischaemic stroke has been described in association with COVID-19. Several pathophysiological mechanisms have been suggested, i.e. prothrombotic state, cardiac injury etc. It was sought to assess the potential association between ischaemic stroke associated with SARS-CoV-2 infection and underlying atherosclerotic lesions. METHODS: A retrospective analysis of stroke related to large vessel occlusion was conducted amongst patients with SARS-CoV-2 infection and underlying mild atherosclerotic disease, between 19 March and 19 April 2020 in six different stroke centers in the Île-de France area, France. RESULTS: The median age was 52 years, median body mass index was 29.5 kg/m2 . All patients displayed previous vascular risk factors such as high blood pressure, diabetes, dyslipidemia or body mass index > 25. The delay between the first respiratory symptoms of COVID-19 and stroke was 11.5 days. At baseline, all had tandem occlusions, i.e. intracerebral and extracerebral thrombus assessed with computed tomography or magnetic resonance imaging. Cases displayed a large thrombus in the cervical carotid artery with underlying mild non-stenosing atheroma, after an etiological workup based on angio-computed tomography or magnetic resonance imaging and/or cervical echography. CONCLUSION: Our study should alert clinicians to scrutinize any new onset of ischaemic stroke during COVID-19 infection, mainly in patients with vascular risk factors or underlying atherosclerotic lesions.

Early successful reperfusion after endovascular therapy reduces malignant middle cerebral artery infarction occurrence in young patients with large diffusion-weighted imaging lesions.

BACKGROUND AND PURPOSE: Malignant middle cerebral artery infarction (MMI) is a severe complication of acute ischaemic stroke (AIS). The aim of our study was to assess whether successful reperfusion after endovascular therapy (EVT) in AIS with clinical and imaging predictors of MMI decreased its occurrence. METHODS: Data were collected between January 2014 and July 2018 in a monocentric prospective AIS registry of patients treated with EVT. Patients selected were <65 years old with severe anterior circulation AIS with a National Institutes of Health Stroke Scale score >15, baseline Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Score ≤ 6 and baseline diffusion-weighted imaging lesion volume >82 mL within 6 h of symptom onset. Successful reperfusion was defined as a Thrombolysis in Cerebral Ischemia score ≥ 2b. Occurrence of MMI was the primary endpoint. RESULTS: A total of 66 EVT-treated patients were included in our study. MMI occurred in 27 patients (41%). In unadjusted analysis, successful reperfusion was associated with fewer MMIs (31.8% vs. 65.0%; P = 0.015) and with more favorable outcome at 3 months (50% vs. 20%; P = 0.023). In multivariate analysis, successful reperfusion was associated with an adjusted odds ratio (95% confidence intervals) of 0.35 (0.10-1.12) for MMI and 2.77 (0.84-10.43) for 3-month favorable outcome occurrence. CONCLUSIONS: Early successful reperfusion performed in patients with AIS with clinical and imaging predictors of MMI was associated with decreased MMI occurrence. Reperfusion status might be considered in evaluating the need for craniectomy in patients with early predictors of MMI.

Angioedema associated with thrombolysis for ischemic stroke: analysis of a case-control study.

BACKGROUND: Bradykinin-mediated angioedema (AE) is a complication associated with thrombolysis for acute ischemic stroke. Risk factors are unknown and management is discussed. OBJECTIVES: To clarify risk factors associated with bradykinin-mediated AE after thrombolysis for acute ischemic stroke. METHODS: In a case-control study conducted at a French reference centre for bradykinin angiœdema, patients with thrombolysis for acute ischemic stroke and a diagnosis of bradykinin-mediated angiœdema, were compared to controls treated with thrombolysis treatment without angiœdema. RESULTS: Fifty-three thrombolysis-related AE were matched to 106 control subjects. The sites of attacks following thrombolysis for ischemic stroke mainly included tongue (34/53, 64%) and lips (26/53, 49%). The upper airways were involved in 37 (70%) cases. Three patients required mechanical ventilation. Patients with bradykinin-mediated angiœdema were more frequently women [33 (62%) vs. 44 (42%); P = 0.01], had higher frequency of prior ischemic stroke [12 (23%) vs. 9 (8%); P = 0.01], hypertension [46 (87%) vs. 70 (66%); P = 0.005], were more frequently treated with angiotensin-converting enzyme inhibitor [37 (70%) vs. 28 (26%); P < 0.001] and were more frequently hospitalized in intensive care medicine [ICU; 11 (21%) vs. 5 (5%); P = 0.004]. In multivariate analysis, factors associated with thrombolysis-related AE were female sex [odds ratio (OR), 3.04; 95% confident interval (CI), 1.32-7.01; P = 0.009] and treatment with angiotensin-converting enzyme inhibitors [(OR), 6.08; 95% (CI), 2.17-17.07; P < 0.001]. CONCLUSIONS: This case-control study points out angiotensin-converting enzyme inhibitors and female sex as risk factors of bradykinin AE associated with thrombolysis for ischemic stroke.

Diagnosis and Prediction of Relapses in Susac Syndrome: A New Use for MR Postcontrast FLAIR Leptomeningeal Enhancement.

BACKGROUND AND PURPOSE: Leptomeningeal enhancement can be found in a variety of neurologic diseases such as Susac Syndrome. Our aim was to assess its prevalence and significance of leptomeningeal enhancement in Susac syndrome using 3T postcontrast fluid-attenuated inversion recovery MR imaging. MATERIALS AND METHODS: From January 2011 to December 2017, nine consecutive patients with Susac syndrome and a control group of 73 patients with multiple sclerosis or clinically isolated syndrome were included. Two neuroradiologists blinded to the clinical and ophthalmologic data independently reviewed MRIs and assessed leptomeningeal enhancement and parenchymal abnormalities. Follow-up MRIs (5.9 MRIs is the mean number per patient over a median period of 46 months) of patients with Susac syndrome were reviewed and compared with clinical and retinal fluorescein angiographic data evaluated by an independent ophthalmologist. Fisher tests were used to compare the 2 groups, and mixed-effects logistic models were used for analysis of clinical and imaging follow-up of patients with Susac syndrome. RESULTS: Patients with Susac syndrome were significantly more likely to present with leptomeningeal enhancement: 5/9 (56%) versus 6/73 (8%) in the control group (P = .002). They had a significantly higher leptomeningeal enhancement burden with ≥3 lesions in 5/9 patients versus 0/73 (P < .001). Regions of leptomeningeal enhancement were significantly more likely to be located in the posterior fossa: 5/9 versus 0/73 (P < .001). Interobserver agreement for leptomeningeal enhancement was good (κ = 0.79). There was a significant association between clinical relapses and increase of both leptomeningeal enhancement and parenchymal lesion load: OR = 6.15 (P = .01) and OR = 5 (P = .02), respectively. CONCLUSIONS: Leptomeningeal enhancement occurs frequently in Susac syndrome and could be helpful for diagnosis and in predicting clinical relapse.

A 1,2,3-triazolate lithium salt with ionic liquid properties at room temperature.

A triethylene glycol-based 1,2,3-triazolate lithium salt with ionic liquid properties at room temperature is synthesized in three steps including copper-catalysed cycloaddition between alkyne-functionalized monomethoxy-triethylene glycol and azidomethyl pivalate, followed by the deprotection of the methyl pivalate group and further lithiation of the 1H-1,2,3-triazole intermediate. The resulting lithium 1,2,3-triazolate is characterized by NMR spectroscopy, differential scanning calorimetry, thermogravimetric analysis, broadband dielectric spectroscopy, electrochemical impedance spectroscopy and cyclic voltamperometry. This approach provides new opportunities for the further development of highly functional molecular and macromolecular lithium salts.

Capecitabine-induced acute toxic leukoencephalopathy.

A 45-year-old woman was treated by Capecitabine (Xeloda®) during 6days for breast cancer with metastatic bone lesions when she presented with nausea, headaches, muscle cramps, dysarthria and swallowing disorders. A stroke was first suspected. Brain CT was normal. MRI showed bilateral and symmetric high signal intensities of deep white matter, corpus callosum and corticospinal tracts on diffusion-weighted imaging and T2 fluid-attenuated inversion recovery (FLAIR) sequence, similar to 5-FU acute leukoencephalopathy. An acute toxic leukoencephalopathy was diagnosed prompting to discontinue capecitabine, which allowed a regression of the symptoms. Though acute toxic leukoencephalopathies with pseudo-stroke presentation have been reported with other chemotherapy agents such as methotrexate or 5-fluorouracil (5-FU), cases of leukoencephalopathy induced by capecitabine are less reported and less well known. This oral precursor of 5-FU is commonly used to treat colorectal, stomach or breast cancers. Neurotoxicity of other 5-FU derivates like cormafur and tergafur have rarely been depicted as well. Although 5-FU-induced leukoencephalopathy is known, the potential toxicity of its precursor should be acknowledged as well. Early detection of chemotherapy-induced toxicity by MRI is crucial as symptoms may be reversible to the condition that chemotherapy is immediately discontinued.

TIPIC Syndrome: Beyond the Myth of Carotidynia, a New Distinct Unclassified Entity.

BACKGROUND AND PURPOSE: The differential diagnosis of acute cervical pain includes nonvascular and vascular causes such as carotid dissection, carotid occlusion, or vasculitis. However, some patients present with unclassified vascular and perivascular changes on imaging previously reported as carotidynia. The aim of our study was to improve the description of this as yet unclassified clinico-radiologic entity. MATERIALS AND METHODS: From January 2009 through April 2016, 47 patients from 10 centers presenting with acute neck pain or tenderness and at least 1 cervical image showing unclassified carotid abnormalities were included. We conducted a systematic, retrospective study of their medical charts and diagnostic and follow-up imaging. Two neuroradiologists independently analyzed the blinded image datasets. RESULTS: The median patient age was 48 years. All patients presented with acute neck pain, and 8 presented with transient neurologic symptoms. Imaging showed an eccentric pericarotidian infiltration in all patients. An intimal soft plaque was noted in 16 patients, and a mild luminal narrowing was noted in 16 patients. Interreader reproducibility was excellent. All patients had complete pain resolution within a median of 13 days. At 3-month follow-up, imaging showed complete disappearance of vascular abnormalities in 8 patients, and a marked decrease in all others. CONCLUSIONS: Our study improved the description of an unclassified, clinico-radiologic entity, which could be described by the proposed acronym: TransIent Perivascular Inflammation of the Carotid artery (TIPIC) syndrome.

Poly(vinyl ester 1,2,3-triazolium)s: a new member of the poly(ionic liquid)s family.

A vinyl ester monomer carrying a pendant 1,2,3-triazole group is synthesized in two steps and polymerized by cobalt-mediated radical polymerization. Subsequent alkylation with N-methyl bis[(trifluoromethyl)sulfonyl]imide affords the corresponding poly(vinyl ester 1,2,3-triazolium). This unprecedented example of poly(vinyl ester ionic liquid) exhibits an ionic conductivity of 9.2 × 10(-7) S cm(-1) at 30 °C.

[Maternal refusal to consent to a cesarean delivery, stillbirth]. / Refus maternel de césarienne d'indication fœtale, mort-né.

The doctor-lawyer perspective that we discuss is a maternal refusal to consent to a cesarean delivery for a fetal indication in June 2011. Despite repeated information of the risks during a three-week hospitalization for pre-eclampsia, after being assured of the proper understanding of the seriousness of the situation by the patient and spouse, and after consideration to transfer to another hospital, the reiterated refusal led to a late fetal extraction resulting in term stillbirth.

[Free floating thrombus on carotid megabulb or suspended bulb: what kind of dysplasia?]. / Thrombus flottant sur un mégabulbe carotidien ou sur un bulbe suspendu, quel type de dysplasie ?

Floating carotid thrombi are a rare cause of stroke mostly associated with atheromatous plaques, cardiogenic emboli, arterial dissections and systemic diseases related to coagulopathic states or iron deficiency anaemia. We report the cases of two patients with stroke and carotid megabulb or suspended bulb associated with floating thrombus. These findings are rarely described probably related to a form of arterial dysplasia and seem to be responsible of local haemodynamic modifications.

[Natural history of adult-onset eIF2B-related disorders: a multicentric survey of 24 cases]. / Histoire naturelle des leucodystrophies avec mutation EIF2B: étude rétrospective multicentrique de 24 cas adultes.

INTRODUCTION: The childhood ataxia with central nervous system hypomyelination-vanishing white matter syndrome (CACH-VWM) was first characterized in children (2-5 years) on clinical and MRI criteria: cerebellospastic signs associated with episodes of rapid deterioration following stress and extensive cavitatingleucoencephalopathy. Causative mutations were found in the five genes encoding the subunits of the eukaryotic initiation factor 2B (eIF2B), involved in protein synthesis and its regulation under cellular stresses. A broad clinical spectrum has been subsequently described from congenital to adult-onset forms leading to the concept of eIF2B-related disorders. Our aim was to describe clinical and brain magnetic resonance imaging characteristics, genetic findings and natural history of patients with adult-onset eIF2B-related disorders. METHODS: The inclusion criteria were based on the presence of EIF2B mutations and a disease onset after the age of 16 years. One patient with an asymptomatic diagnosis was also included. Clinical and MRI findings were retrospectively recorded in all patients. This multicentric study included 24 patients from 22 families. RESULTS: A sex-ratio imbalance was noted (male/female=5/19). The mean age of onset was 30 years (range 12-62). Initial symptoms were neurologic (n=20), psychiatric (n=3) and ovarian failure (n=6). During follow-up (mean: 11 years, range 2-35 years), two patients died. Of the 22 survivors, 67% showed a decline in their cognitive functions and mean EDSS was 5.6 (range=0-9.5). One case remained asymptomatic. Stress worsened clinical symptoms in 33% of the patients. Magnetic resonance imaging findings consisted of cerebral atrophy (92%), extensive cystic leucoencephalopathy (83%), corpus callosum involvement (92%) and cerebellar (37%) T2-weighted hyperintensities. Most patients (83%) showed mutations in the EIF2B5 gene. The recurrent p.Arg113His-eIF2Be mutation was found at a homozygous state in 58% of the 24 eIF2B-mutated patients. CONCLUSION: eIF2B-related disorder is probably underestimated as an adult-onset inherited leucoencephalopathy. Cerebral atrophy is constant, whereas the typical vanishing of the white matter can be absent. Functional and cognitive prognosis remains severe. Molecular diagnosis is facilitated for these forms by screening for the recurrent p.Arg113His-eIF2Be mutation.

[Intracranial hypertension and lupus]. / Hypertension intracrânienne et lupus.

INTRODUCTION: Idiopathic intracranial hypertension (IH) occurs most commonly in women and overweight subjects. It must be reported associated to general diseases, like systemic lupus erythematosus (SLE). METHODS: We report an observation of a patient with lupus complicated by glomerulonephritis and IH. OBSERVATION: A 29 years old woman, without overweight, was followed for a SLE with skin and arthritic involvement . Four years after onset, a renal complication appeared with severe nephrotic syndrome. Six weeks after, bilateral papillar oedema was discovered, revealing an IH, as the patient was treated by oral steroids at 1mg/kg/d and bimonthly intravenous cyclophosphamide. The patient was completely asymptomatic. Brain MRI with veino-RMN was normal, without cerebral venous thrombosis. Lumbar punction showed an elevated opening pressure of 30,5 cmH(2)0 but with normal cerebrospinal fluid (CSF) contents. Evacuation of 30 mL of CSF and immunosuppressive treatment allowed symptoms regression. DISCUSSION/CONCLUSION: Twenty-seven cases of IH associated to SLE with nephritis have been reported in literature. Young women are more frequently involved with in half of cases a diffuse proliferative glomerulonephritis. Predisposing factors, like anaemia, must be associated. IH allows SLE diagnose in more than the third of the cases. Then, SLE has to be searched as an etiology of IH, in particular in non-obese patients and when nephritis is associated.

Magnetic resonance spectroscopy findings in a case of hyperglycaemic hemianopia.

INTRODUCTION: Patients with nonketotic hyperglycaemia may present with neurological manifestations, including hemianopia. Thus far, the pathophysiology of such neurological events remains unknown, although the findings on magnetic resonance imaging (MRI) may help to elucidate the underlying mechanisms. CASE REPORT: This report describes a patient who had an episode of homonymous hemianopia, which coincided with a state of nonketotic hyperglycaemia. Initial MRI showed hypointense areas on T2-weighted and FLAIR sequences, involving the internal portion of the right occipital cortex and adjacent white matter, with mild hyperintensity on diffusion-weighted imaging. Magnetic resonance spectroscopy revealed significant increases in cerebral metabolites. Dramatic clinical and neuroimaging improvements were progressively observed over 3 weeks, following rehydration and normalization of blood glucose levels with insulin therapy. CONCLUSION: In this patient, magnetic resonance spectroscopy was used in combination with other neuroimaging methods and clinical evidence to suggest that hyperosmolality leading to intracellular dehydration in localized brain regions should be considered a potential underlying mechanism responsible for reversible neurological symptoms in nonketotic hyperglycaemia.

[Susac syndrome: study of five cases]. / Syndrome de Susac: étude de cinq cas.

INTRODUCTION: Susac syndrome is a rare microangiopathy, responsible for small cerebral, retinal and cochlear infarcts. The classic clinical triad includes multiple neurologic signs (from headaches to coma), retinal branch occlusions and sensorineural hearing loss. METHODS: We report a series of five patients with Susac syndrome followed in our department from 1997 to 2007. RESULTS: There were four women and one man (mean age at onset: 35.2 years). Clinical symptoms at onset were neurological (n=1), ophthalmological (n=1), auditory (n=1) and clinical triad (n=2). Neurologic symptoms included encephalopathy (n=2), headache (n=5), transient ischemic attacks (n=1). Brain MRI showed T2 lesions in the white and grey matter, corpus callosum and gadolinium-enhanced punctiform lesions. Cerebrospinal fluid contained an elevated protein level in three cases. Immunologic treatments (steroids [n=4], cylophosphamid [n=3], intravenous immunoglobulins [n=5]) associated with aspirin and/or oral anticoagulants, despite early relapses (n=2), led to dramatic clinical improvement (n=5). CONCLUSION: Due to its polymorphism the SS is difficult to diagnose when the clinical triad is lacking. In the absence of clinical trial and consensus treatment is empiric and based on supposed pathogenesis.

[Brain hypoperfusion revealed by an ocular ischemic syndrome]. / Bas débit cérébral révélé par une ischémie oculaire.

We report the case of a 59-year-old female presenting an ocular ischemic syndrome caused by occlusion of the internal carotid artery. MRI showed multiple previous episodes of stroke. Therapy consisted in stopping the antihypertensive medication in order to stabilize the residual cerebral perfusion pressure and initiating statin and antiaggregant therapy.