Brain microstructure and connectivity in COVID-19 patients with olfactory or cognitive impairment.

INTRODUCTION: The COVID-19 pandemic has affected millions worldwide, causing mortality and multi-organ morbidity. Neurological complications have been recognized. This study aimed to assess brain structural, microstructural, and connectivity alterations in patients with COVID-19-related olfactory or cognitive impairment using post-acute (time from onset: 264[208-313] days) multi-directional diffusion-weighted MRI (DW-MRI). METHODS: The study included 16 COVID-19 patients with cognitive impairment (COVID-CM), 35 COVID-19 patients with olfactory disorder (COVID-OD), and 14 controls. A state-of-the-art processing pipeline was developed for DW-MRI pre-processing, mean diffusivity and fractional anisotropy computation, fiber density and cross-section analysis, and tractography of white-matter bundles. Brain parcellation required for probing network connectivity, region-specific microstructure and volume, and cortical thickness was based on T1-weighted scans and anatomical atlases. RESULTS: Compared to controls, COVID-CM patients showed overall gray matter atrophy (age and sex corrected p = 0.004), and both COVID-19 patient groups showed regional atrophy and cortical thinning. Both groups presented an increase in gray matter mean diffusivity (corrected p = 0.001), decrease in white matter fiber density and cross-section (corrected p < 0.05), , and COVID-CM patients also displayed an overall increased diffusivity (p = 0.022) and decreased anisotropy (corrected p = 0.038) in white matter. Graph-based analysis revealed reduced network modularity, with an extensive pattern of connectivity increase, in conjunction with a localized reduction in a few connections, mainly located in the left hemisphere. The left cingulate, anterior cingulate, and insula were primarily involved. CONCLUSION: Expanding upon previous findings, this study further investigated significant alterations in brain morphology, microstructure, and connectivity in COVID-19 patients with olfactory or cognitive disfunction. These findings suggest underlying neurodegeneration, neuroinflammation, and concomitant compensatory mechanisms. Future longitudinal studies are required to monitor the alterations over time and assess their transient or permanent nature.

Neuroradiological manifestations in hospitalized patients with COVID-19: An Italian national multicenter study on behalf of AINR (Associazione Italiana di Neuroradiologia) and SIRM (Società Italiana di Radiologia Medica).

PURPOSE: This multicentric study aims to characterize and assess the occurrence of neuroradiological findings among patients with SARS-CoV-2 infection during the first Italian wave of the pandemic outbreak. MATERIALS AND METHODS: Patients' data were collected between May 2020 and June 2020. Clinical and laboratory data, chest imaging, brain CT, and MRI imaging were included. Acquired data were centralized and analyzed in two hospitals: ASST Spedali Civili, Brescia, and IRRCS San Raffaele Research Hospital, Milan, Italy. COVID-19 patients were classified into two different subgroups, vascular and nonvascular. The vascular pattern was further divided into ischemic and hemorrhagic stroke groups. RESULTS: Four hundred and fifteen patients from 20 different Italian Centers were enrolled in the study. The most frequent symptom was focal neurological deficit, found in 143 patients (34.5%). The most frequent neuroradiological finding was ischemic stroke in 122 (29.4%) patients. Forty-four (10.6%) patients presented a cerebral hemorrhage. Forty-seven patients had non-stroke neuroimaging lesions (11.3%). The most common was PRES-like syndrome (28%), SWI hypointensities (22%), and encephalitis (19%). The stroke group had higher CAD risk (37.5% vs 20%, p = .016) and higher D-dimer levels (1875 ng/mL vs 451 ng/mL, p < .001) compared to the negative group. CONCLUSION: Our study describes the biggest cohort study in Italy on brain imaging of COVID-19 patients and confirms that COVID-19 patients are at risk of strokes, possibly due to a pro-thrombotic microenvironment. Moreover, apart from stroke, the other neuroradiological patterns described align with the ones reported worldwide.

Cerebral autoregulation in traumatic brain injury: ultra-low-frequency pressure reactivity index and intracranial pressure across age groups.

BACKGROUND: The ultra-low-frequency pressure reactivity index (UL-PRx) has been established as a surrogate method for bedside estimation of cerebral autoregulation (CA). Although this index has been shown to be a predictor of outcome in adult and pediatric patients with traumatic brain injury (TBI), a comprehensive evaluation of low sampling rate data collection (0.0033 Hz averaged over 5 min) on cerebrovascular reactivity has never been performed. OBJECTIVE: To evaluate the performance and predictive power of the UL-PRx for 12-month outcome measures, alongside all International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) models and in different age groups. To investigate the potential for optimal cerebral perfusion pressure (CPPopt). METHODS: Demographic data, IMPACT variables, in-hospital mortality, and Glasgow Outcome Scale Extended (GOSE) at 12 months were extracted. Filtering and processing of the time series and creation of the indices (cerebral intracranial pressure (ICP), cerebral perfusion pressure (CPP), UL-PRx, and deltaCPPopt (ΔCPPopt and CPPopt-CPP)) were performed using an in-house algorithm. Physiological parameters were assessed as follows: mean index value, % time above threshold, and mean hourly dose above threshold. RESULTS: A total of 263 TBI patients were included: pediatric (17.5% aged ≤ 16 y) and adult (60.5% aged > 16 and < 70 y and 22.0% ≥ 70 y, respectively) patients. In-hospital and 12-month mortality were 25.9% and 32.7%, respectively, and 60.0% of patients had an unfavorable outcome at 12 months (GOSE). On univariate analysis, ICP, CPP, UL-PRx, and ΔCPPopt were associated with 12-month outcomes. The cutoff of ~ 20-22 for mean ICP and of ~ 0.30 for mean UL-PRx were confirmed in all age groups, except in patients older than 70 years. Mean UL-PRx remained significantly associated with 12-month outcomes even after adjustment for IMPACT models. This association was confirmed in all age groups. UL-PRx resulted associate with CPPopt. CONCLUSIONS: The study highlights UL-PRx as a tool for assessing CA and valuable outcome predictor for TBI patients. The results emphasize the potential clinical utility of the UL-PRx and its adaptability across different age groups, even after adjustment for IMPACT models. Furthermore, the correlation between UL-PRx and CPPopt suggests the potential for more targeted treatment strategies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05043545, principal investigator Paolo Gritti, date of registration 2021.08.21.

An optimized 1.5 Tesla MRI protocol of the brachial plexus.

PURPOSE: Creating an effective MRI protocol for examining the brachial plexus poses significant challenges, and despite the abundance of protocols in the literature, there is a lack of reference standards for basic sequences and essential parameters needed for replication. The aim of this study is to establish a reproducible 1.5 T brachial plexus imaging protocol, including patient positioning, coil selection, imaging planes, and essential sequence parameters. METHODS: We systematically investigated MRI sequences, testing each parameter through in vivo experiments, examining their effects on signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), visual quality scores, and acquisition time. Sequences were refined based on optimal quality and timing scores. The final protocol was tested on scanners from two other vendors for reliability. RESULTS: The final protocol included a combination of 2D turbo-spin-echo and 3D SPACE T1, SPACE STIR, and VIBE DIXON sequences. Recommendations for imaging planes, phase encoding, field of view, TR, TE, resolution, number of slices, slice thickness, fat and blood suppression, and acceleration strategies are provided. The protocol was successfully translated to other vendor's scanners with comparable quality. CONCLUSION: We present an optimized protocol detailing the essential parameters for reproducibility. Our comprehensive list of experiments describes the impact of each parameter on image quality and scan time, addressing common artifacts and potential solutions. This protocol can benefit both young radiologists new to the field and experienced professionals seeking to refine their existing protocols.

Neuromuscular imaging in clinical practice: an ESNR survey of 30 centers.

PURPOSE: We assessed the current clinical imaging practice in the primary evaluation of neuromuscular disorders (NMD), with respect to standardized imaging, evaluation and reporting through a European and extra-European-wide survey. METHODS: An online questionnaire was emailed to all European Society of Neuroradiology (ESNR) members (n = 1662) who had expressed their interest in NMD. The questionnaire featured 40 individual items. Information was gathered on the context of the practices, available and preferred imaging modalities, applied imaging protocols and standards for interpretation, reporting and communication. RESULTS: A total of 30 unique entries from European and extra-European academic and non-academic institutions were received. Of these, 70% were neuroradiologists, 23% general radiologists and 7% musculoskeletal radiologists. Of the 30 responding institutes, 40% performed from 20 to 50 neuromuscular scans per year for suspected NMD. The principal modality used for a suspected myopathy was magnetic resonance imaging (MRI) (50%) or "mainly MRI" (47%). The primary imaging modality used for the evaluation of patients suspected of a neuropathy was MRI in 63% of all institutions and "mainly MRI" in 37%. For both muscle and nerve pathology, pelvic girdle and inferior limbs are the most scanned parts of the body (28%), followed by the thigh and leg (24%), whole body MR (24%), scapular girdle (16%), and the thigh in just 8% of institutions. Multiplanar acquisitions were performed in 50% of institutions. Convectional sequences used for muscle MRI included T2-STIR (88%), 2D T1weighted (w) (68%), T1 Dixon or equivalent (52%), T2 Dixon (40%), DWI (36%), 2D T2w (28%), T1 3D and T2 3D (20% respectively). For nerve MRI conventional sequences included T2-STIR (80%), DWI (56%), T2 3D (48%), 2D T2w (48%), T1 3D (44%), T1 Dixon or equivalent (44%), 2D T1 (36%), T2 Dixon (28%). Quantitative sequences were used regularly by 40% respondents. While only 28% of institutions utilized structured reports, a notable 88% of respondents expressed a desire for a standardized consensus structured report. Most of the respondents (93%) would be interested in a common MRI neuromuscular protocol and would like to be trained (87%) by the ESNR society with specific neuromuscular sessions in European annual meetings. CONCLUSIONS: Based on the survey findings, we can conclude that the current approach to neuromuscular imaging varies considerably among European and extra-European countries, both in terms of image acquisition and post-processing. Some of the challenges identified include the translation of research achievements (related to advanced imaging) into practical applications in a clinical setting, implementation of quantitative imaging post-processing techniques, adoption of structured reporting methods, and communication with referring physicians.

Neuroimaging findings in 4342 hospitalized COVID-19 subjects: A multicenter report from the United States and Europe.

BACKGROUND AND PURPOSE: To determine the incidence of acute neuroimaging (NI) findings and comorbidities in the coronavirus disease of 2019 (COVID-19)-infected subjects in seven U.S. and four European hospitals. METHODS: This is a retrospective study of COVID-19-positive subjects with the following inclusion criteria: age >18, lab-confirmed COVID-19 infection, and acute NI findings (NI+) attributed to COVID-19 on CT or MRI brain. NI+ and comorbidities in total hospitalized COVID-19-positive (TN) subjects were assessed. RESULTS: A total of 37,950 COVID-19-positive subjects were reviewed and 4342 underwent NI. NI+ incidence in subjects with NI was 10.1% (442/4342) including 7.9% (294/3701) in the United States and 22.8% (148/647) in Europe. NI+ incidence in TN was 1.16% (442/37,950). In NI (4342), incidence of ischemic stroke was 6.4% followed by intracranial hemorrhage (ICH) (3.8%), encephalitis (0.5%), sinus venous thrombosis (0.2%), and acute disseminated encephalomyelitis (ADEM) (0.2%). White matter involvement was seen in 57% of NI+. Hypertension was the most common comorbidity (54%) before cardiac disease (28.8%) and diabetes mellitus (27.7%). Cardiac disease (p < .025), diabetes (p < .014), and chronic kidney disease (p < .012) were more common in the United States. CONCLUSION: This multicenter, multinational study investigated the incidence and spectrum of NI+ in 37,950 hospitalized adult COVID-19 subjects including regional differences in incidences of NI+, associated comorbidities, and other demographics. NI+ incidence in TN was 1.16% including 0.95% in the United States and 2.09% in Europe. ICH, encephalitis, and ADEM were common in Europe, while ischemic strokes were more common in the United States. In this cohort, incidence and distribution of NI+ helped characterize the neurological complications of COVID-19.

Brain diffusion alterations in patients with COVID-19 pathology and neurological manifestations.

BACKGROUND AND OBJECTIVE: COVID-19 neurological manifestations have been progressively recognized. Among available MRI techniques, diffusion weighted imaging (DWI) shows promise to study microstructure, inflammation, and edema. Previous DWI studies reported alterations in brain diffusivity in COVID-19 patients, as assessed by morphologic evaluation of brain DWI scans only. The aim of this study was to assess and quantify brain diffusion alterations in COVID-19 patients with neurological manifestations. METHODS: 215 COVID-19 patients with neurological manifestations (olfactory and/or other neurological disorders) and 36 normal controls were compared and studied with DWI and T1-weighted MRI scans. MRI scans were processed by a semi-automatic processing procedure specifically developed for the purpose of this study, and the Apparent Diffusion Coefficient (ADC) was quantified in different brain tissues and individual white matter (WM) and gray matter (GM) regions. Differences in ADC values were assessed between COVID-19 patients and normal controls, as well as in the COVID-19 patient population grouped by hospitalization and neurological symptoms. RESULTS: Among COVID-19 patients (median [IQR] = 52 [42 - 60] years of age, 58 % females), 91 were hospitalized and 26 needed intensive care. 84 patients had hyposmia/ageusia only, while 131 ones showed other neurological disorders. COVID-19 patients showed significantly increased ADC values in the WM and in several GM regions (p < 0.001). ADC values were significantly correlated with MRI time from disease onset (p < 0.05). Hospitalized patients showed significantly higher ADC alteration than non-hospitalized patients in all brain tissues; similarly, COVID-19 patients with neurological disorders showed significantly higher ADC values than those with olfactory loss only. ADC alteration was highest in patients with cognitive or memory disorder and in those with encephalitis or meningitis. ADC values were neither associated with the duration of hospitalization nor with the need for intensive care. CONCLUSION: Current findings suggest DWI potential as a non-invasive marker of neuroinflammation in COVID-19, and the transient nature of the same. Future longitudinal studies are needed to confirm our findings.

MRI evidence of olfactory system alterations in patients with COVID-19 and neurological symptoms.

BACKGROUND AND OBJECTIVE: Despite olfactory disorders being among the most common neurological complications of coronavirus disease 2019 (COVID-19), their pathogenesis has not been fully elucidated yet. Brain MR imaging is a consolidated method for evaluating olfactory system's morphological modification, but a few quantitative studies have been published so far. The aim of the study was to provide MRI evidence of olfactory system alterations in patients with COVID-19 and neurological symptoms, including olfactory dysfunction. METHODS: 196 COVID-19 patients (median age: 53 years, 56% females) and 39 controls (median age 55 years, 49% females) were included in this cross-sectional observational study; 78 of the patients reported olfactory loss as the only neurological symptom. MRI processing was performed by ad-hoc semi-automatic processing procedures. Olfactory bulb (OB) volume was measured on T2-weighted MRI based on manual tracing and normalized to the brain volume. Olfactory tract (OT) median signal intensity was quantified on fluid attenuated inversion recovery (FLAIR) sequences, after preliminary intensity normalization. RESULTS: COVID-19 patients showed significantly lower left, right and total OB volumes than controls (p < 0.05). Age-related OB atrophy was found in the control but not in the patient population. No significant difference was found between patients with olfactory disorders and other neurological symptoms. Several outliers with abnormally high OT FLAIR signal intensity were found in the patient group. CONCLUSIONS: Brain MRI findings demonstrated OB damage in COVID-19 patients with neurological complications. Future longitudinal studies are needed to clarify the transient or permanent nature of OB atrophy in COVID-19 pathology.

Antisense Morpholino-Based In Vitro Correction of a Pseudoexon-Generating Variant in the SGCB Gene.

Limb-girdle muscular dystrophies (LGMD) are clinically and genetically heterogenous presentations displaying predominantly proximal muscle weakness due to the loss of skeletal muscle fibers. Beta-sarcoglycanopathy (LGMDR4) results from biallelic molecular defects in SGCB and features pediatric onset with limb-girdle involvement, often complicated by respiratory and heart dysfunction. Here we describe a patient who presented at the age of 12 years reporting high creatine kinase levels and onset of cramps after strenuous exercise. Instrumental investigations, including a muscle biopsy, pointed towards a diagnosis of beta-sarcoglycanopathy. NGS panel sequencing identified two variants in the SGCB gene, one of which (c.243+1548T>C) was found to promote the inclusion of a pseudoexon between exons 2 and 3 in the SGCB transcript. Interestingly, we detected the same genotype in a previously reported LGMDR4 patient, deceased more than twenty years ago, who had escaped molecular diagnosis so far. After the delivery of morpholino oligomers targeting the pseudoexon in patient-specific induced pluripotent stem cells, we observed the correction of the physiological splicing and partial restoration of protein levels. Our findings prompt the analysis of the c.243+1548T>C variant in suspected LGMDR4 patients, especially those harbouring monoallelic SGCB variants, and provide a further example of the efficacy of antisense technology for the correction of molecular defects resulting in splicing abnormalities.

Cerebral Microbleeds Assessment and Quantification in COVID-19 Patients With Neurological Manifestations.

It is increasingly acknowledged that Coronavirus Disease 2019 (COVID-19) can have neurological manifestations, and cerebral microbleeds (CMBs) have been observed in this setting. The aim of this study was to characterize CMBs patterns on susceptibility-weighted imaging (SWI) in hospitalized patients with COVID-19 with neurological manifestations. CMBs volume was quantified and correlated with clinical and laboratory parameters. The study included patients who were hospitalized due to COVID-19, exhibited neurological manifestations, and underwent a brain MRI between March and May 2020. Neurological, clinical, and biochemical variables were reported. The MRI was acquired using a 3T scanner, with a standardized protocol including SWI. Patients were divided based on radiological evidence of CMBs or their absence. The CMBs burden was also assessed with a semi-automatic SWI processing procedure specifically developed for the purpose of this study. Odds ratios (OR) for CMBs were calculated using age, sex, clinical, and laboratory data by logistic regression analysis. Of the 1,760 patients with COVID-19 admitted to the ASST Papa Giovanni XXIII Hospital between 1 March and 31 May 2020, 116 exhibited neurological symptoms requiring neuroimaging evaluation. Of these, 63 patients underwent brain MRI and were therefore included in the study. A total of 14 patients had radiological evidence of CMBs (CMBs+ group). CMBs+ patients had a higher prevalence of CSF inflammation (p = 0.020), a higher white blood cell count (p = 0.020), and lower lymphocytes (p = 0.010); the D-dimer (p = 0.026), LDH (p = 0.004), procalcitonin (p = 0.002), and CRP concentration (p < 0.001) were higher than in the CMBs- group. In multivariable logistic regression analysis, CRP (OR = 1.16, p = 0.011) indicated an association with CMBs. Estimated CMBs volume was higher in females than in males and decreased with age (Rho = -0.38; p = 0.18); it was positively associated with CRP (Rho = 0.36; p = 0.22), and negatively associated with lymphocytes (Rho = -0.52; p = 0.07). CMBs are a frequent imaging finding in hospitalized patients with COVID-19 with neurological manifestations and seem to be related to pro-inflammatory status.

Neuroimaging in patients with COVID-19: a neuroradiology expert group consensus.

Neurological and neuroradiological manifestations in patients with COVID-19 have been extensively reported. Available imaging data are, however, very heterogeneous. Hence, there is a growing need to standardise clinical indications for neuroimaging, MRI acquisition protocols, and necessity of follow-up examinations. A NeuroCovid working group with experts in the field of neuroimaging in COVID-19 has been constituted under the aegis of the Subspecialty Committee on Diagnostic Neuroradiology of the European Society of Neuroradiology (ESNR). The initial objectives of this NeuroCovid working group are to address the standardisation of the imaging in patients with neurological manifestations of COVID-19 and to give advice based on expert opinion with the aim of improving the quality of patient care and ensure high quality of any future clinical studies. KEY POINTS: • In patients with COVID-19 and neurological manifestations, neuroimaging should be performed in order to detect underlying causal pathology. • The basic MRI recommended protocol includes T2-weighted, FLAIR (preferably 3D), and diffusion-weighted images, as well as haemorrhage-sensitive sequence (preferably SWI), and at least for the initial investigation pre and post-contrast T1 weighted-images. • 3D FLAIR should be acquired after gadolinium administration in order to optimise the detection of leptomeningeal contrast enhancement.

SARS-CoV-2 infection and acute ischemic stroke in Lombardy, Italy.

OBJECTIVE: To characterize patients with acute ischemic stroke related to SARS-CoV-2 infection and assess the classification performance of clinical and laboratory parameters in predicting in-hospital outcome of these patients. METHODS: In the setting of the STROKOVID study including patients with acute ischemic stroke consecutively admitted to the ten hub hospitals in Lombardy, Italy, between March 8 and April 30, 2020, we compared clinical features of patients with confirmed infection and non-infected patients by logistic regression models and survival analysis. Then, we trained and tested a random forest (RF) binary classifier for the prediction of in-hospital death among patients with COVID-19. RESULTS: Among 1013 patients, 160 (15.8%) had SARS-CoV-2 infection. Male sex (OR 1.53; 95% CI 1.06-2.27) and atrial fibrillation (OR 1.60; 95% CI 1.05-2.43) were independently associated with COVID-19 status. Patients with COVID-19 had increased stroke severity at admission [median NIHSS score, 9 (25th to75th percentile, 13) vs 6 (25th to75th percentile, 9)] and increased risk of in-hospital death (38.1% deaths vs 7.2%; HR 3.30; 95% CI 2.17-5.02). The RF model based on six clinical and laboratory parameters exhibited high cross-validated classification accuracy (0.86) and precision (0.87), good recall (0.72) and F1-score (0.79) in predicting in-hospital death. CONCLUSIONS: Ischemic strokes in COVID-19 patients have distinctive risk factor profile and etiology, increased clinical severity and higher in-hospital mortality rate compared to non-COVID-19 patients. A simple model based on clinical and routine laboratory parameters may be useful in identifying ischemic stroke patients with SARS-CoV-2 infection who are unlikely to survive the acute phase.

Out-of-Frame Mutations in ACTN2 Last Exon Cause a Dominant Distal Myopathy With Facial Weakness.

BACKGROUND AND OBJECTIVES: To clinically, genetically, and histopathologically characterize patients presenting with an unusual combination of distal myopathy and facial weakness, without involvement of upper limb or shoulder girdle muscles. METHODS: Two families with a novel form of actininopathy were identified. Patients had been followed up over 10 years. Their molecular genetic diagnosis was not clear after extensive investigations, including analysis of candidate genes and FSHD1-related D4Z4 repeats. RESULTS: Patients shared a similar clinical phenotype and a common pattern of muscle involvement. They presented with a very slowly progressive myopathy involving anterior lower leg and facial muscles. Muscle MRI finding showed complete fat replacement of anterolateral compartment muscles of the lower legs with variable involvement of soleus and gastrocnemius but sparing thigh muscles. Muscle biopsy showed internalized nuclei, myofibrillar disorganization, and rimmed vacuoles. High-throughput sequencing identified in each proband a heterozygous single nucleotide deletion (c.2558del and c.2567del) in the last exon of the ACTN2 gene. The deletions are predicted to lead to a novel but unstructured slightly extended C-terminal amino acid sequence. DISCUSSION: Our findings indicate an unusual form of actininopathy with specific molecular and clinical features. Actininopathy should be considered in the differential diagnosis of distal myopathy combined with facial weakness.

The symptomatology of cerebrospinal fluid HIV RNA escape: a large case-series.

OBJECTIVE: To characterize the clinical, laboratory and radiological characteristics of persons with HIV (PWH) presenting with cerebrospinal fluid (CSF) HIV RNA escape. DESIGN: Retrospective case review of PWH presenting with symptomatic CSF HIV RNA escape at seven tertiary HIV clinical sites in the United Kingdom and Italy. METHOD: PWH with symptomatic CSF HIV RNA escape episodes were identified and data obtained from medical records. CSF HIV RNA escape was defined as quantifiable CSF HIV RNA in unquantifiable plasma HIV RNA or CSF HIV RNA greater than plasma HIV RNA in cases where plasma HIV RNA was quantifiable. The onset of clinical symptoms was classified as acute (<2 weeks-6 months), or chronic (>6 months) and differences in presentation in those with CSF HIV RNA below and above 1000 copies/ml determined. RESULTS: We identified 106 PWH with CSF HIV RNA escape (65 male); 68 (64%) PWH had acute presentations and 38 (36%) had chronic presentations. Cognitive decline (n = 54; 50.9%), confusion (n = 20; 18.9%) and headache (n = 28; 26.4%) were the most common presentations, with cognitive decline being more common in PWH who presented chronically compared with PWH who presented acutely (73.7% vs. 35.3%, P = 0.0002). Sixty PWH had CSF HIV RNA at least 1000 copies/ml and presented more frequently with confusion (n = 15/60; 25.0%) compared with PWH with CSF HIV RNA less than 1000 copies/ml at presentation (n = 5/46; 10.9%; P = 0.03). CONCLUSION: Cognitive decline, confusion and headache are the most frequent presenting symptoms of CSF HIV RNA escape and their relative frequency varied according to symptom onset and CSF HIV RNA concentration.

Impact of SARS-CoV-2 on reperfusion therapies for acute ischemic stroke in Lombardy, Italy: the STROKOVID network.

Whether and how SARS-CoV-2 outbreak affected in-hospital acute stroke care system is still matter of debate. In the setting of the STROKOVID network, a collaborative project between the ten centers designed as hubs for the treatment of acute stroke during SARS-CoV-2 outbreak in Lombardy, Italy, we retrospectively compared clinical features and process measures of patients with confirmed infection (COVID-19) and non-infected patients (non-COVID-19) who underwent reperfusion therapies for acute ischemic stroke. Between March 8 and April 30, 2020, 296 consecutive patients [median age, 74 years (interquartile range (IQR), 62-80.75); males, 154 (52.0%); 34 (11.5%) COVID-19] qualified for the analysis. Time from symptoms onset to treatment was longer in the COVID-19 group [230 (IQR 200.5-270) minutes vs. 190 (IQR 150-245) minutes; p = 0.007], especially in the first half of the study period. Patients with COVID-19 who underwent endovascular thrombectomy had more frequently absent collaterals or collaterals filling ≤ 50% of the occluded territory (50.0% vs. 16.6%; OR 5.05; 95% CI 1.82-13.80) and a lower rate of good/complete recanalization of the primary arterial occlusive lesion (55.6% vs. 81.0%; OR 0.29; 95% CI 0.10-0.80). Post-procedural intracranial hemorrhages were more frequent (35.3% vs. 19.5%; OR 2.24; 95% CI 1.04-4.83) and outcome was worse among COVID-19 patients (in-hospital death, 38.2% vs. 8.8%; OR 6.43; 95% CI 2.85-14.50). Our findings showed longer delays in the intra-hospital management of acute ischemic stroke in COVID-19 patients, especially in the early phase of the outbreak, that likely impacted patients outcome and should be the target of future interventions.

Adoptive Transfer of JC Virus-Specific T Lymphocytes for the Treatment of Progressive Multifocal Leukoencephalopathy.

OBJECTIVE: Progressive multifocal leukoencephalopathy (PML) is still burdened by high mortality in a subset of patients, such as those affected by hematological malignancies. The aim of this study was to analyze the safety and carry out preliminary evaluation of the efficacy of polyomavirus JC (JCPyV)-specific T cell therapy in a cohort of hematological patients with PML. METHODS: Between 2014 and 2019, 9 patients with a diagnosis of "definite PML" according to the 2013 consensus who were showing progressive clinical deterioration received JCPyV-specific T cells. Cell lines were expanded from autologous or allogenic peripheral blood mononuclear cells by stimulation with JCPyV antigen-derived peptides. RESULTS: None of the patients experienced treatment-related adverse events. In the evaluable patients, an increase in the frequency of circulating JCPyV-specific lymphocytes was observed, with a decrease or clearance of JCPyV viral load in cerebrospinal fluid. In responsive patients, transient appearance of punctate areas of contrast enhancement within, or close to, PML lesions was observed, which was interpreted as a sign of immune control and which regressed spontaneously without the need for steroid treatment. Six of 9 patients achieved PML control, with 5 alive and in good clinical condition at their last follow-up. INTERPRETATION: Among other novel treatments, T cell therapy is emerging as a viable treatment option in patients with PML, particularly for those not amenable to restoration of specific immunity. Neurologists should be encouraged to refer PML patients to specialized centers to allow access to this treatment strategy. ANN NEUROL 2021;89:769-779.

The risk of infection in patients with multiple sclerosis treated with disease-modifying therapies: A Delphi consensus statement.

The risk of infection associated with immunomodulatory or immunosuppressive disease-modifying drugs (DMDs) in patients with multiple sclerosis (MS) has been increasingly addressed in recent scientific literature. A modified Delphi consensus process was conducted to develop clinically relevant, evidence-based recommendations to assist physicians with decision-making in relation to the risks of a wide range of infections associated with different DMDs in patients with MS. The current consensus statements, developed by a panel of experts (neurologists, infectious disease specialists, a gynaecologist and a neuroradiologist), address the risk of iatrogenic infections (opportunistic infections, including herpes and cryptococcal infections, candidiasis and listeria; progressive multifocal leukoencephalopathy; human papillomavirus and urinary tract infections; respiratory tract infections and tuberculosis; hepatitis and gastrointestinal infections) in patients with MS treated with different DMDs, as well as prevention strategies and surveillance strategies for the early identification of infections. In the discussion, more recent data emerged in the literature were taken into consideration. Recommended risk reduction and management strategies for infections include screening at diagnosis and before starting a new DMD, prophylaxis where appropriate, monitoring and early diagnosis.