Aseptic meningitis and Fabry disease.

OBJECTIVE: Fabry disease is caused by enzymatic defects in alpha-galactosidase A that leads to the accumulation of glycosphingolipids throughout the body, resulting in a multisystemic disorder. The most common neurological manifestations are neuropathic pain, autonomic nervous system dysfunction and strokes, but some rarer neurological manifestations exist. Among these, aseptic meningitis is a possible complication. Our objectives were to measure the prevalence of this complication in a cohort of patients with Fabry disease, and to describe its clinical features. METHODS: We conducted a retrospective review of Fabry disease patients followed at our tertiary referral center between 1995 and September 2023 with at least one episode of meningitis, and performed a systematic review to identify similar published cases. RESULTS: Four patients out of 107 (3.7%) had at least one episode of aseptic meningitis. Our systematic review identified 25 other observations. The median age of these 29 patients was 29.0 years, the median cerebrospinal fluid leukocyte count was 24 cells/mm3 with a predominance of lymphocytes in 64.7% of cases. In 82.8% of the patients, the diagnosis of Fabry disease was unknown before the meningitis. Large artery stenosis was present in 17.2% of patients and 57.1% of patients had a recent stroke concomitant with the meningitis. Several differential diagnoses were evoked, such as multiple sclerosis or central nervous system vasculitis. INTERPRETATION: Our study suggests that Fabry disease should be considered as a cause of aseptic meningitis. The pathophysiological mechanisms underlying meningeal inflammation remain largely unknown but may reflect the dysregulation of pro-inflammatory signaling pathways.

Limb arteries involvement assessed by FDG/PET CT at diagnosis of giant cell arteritis and risk of relapse: An observational study.

INTRODUCTION: Steroids and anti-IL6 biotherapy are highly effective in obtaining remission in patients with giant cell arteritis (GCA) but the risk of relapses remains high. We aimed to identify predictors of relapse in GCA. METHODS: All consecutive patients admitted with a new diagnosis of GCA - according to the 2022 American College of Rheumatology/EULAR (ACR/EULAR) classification criteria - between May 2011 and May 2022 were eligible for this study. The primary outcome was the GCA relapse rate over the 36-months follow up. Factors associated with the primary outcome and time to first relapse were analyzed. RESULTS: One hundred and eight patients (74 [69-81] years, 64.8% women) with a new diagnosis of GCA were studied. GCA was biopsy-proven in 65 (60.2%) cases. Ninety-eight (90.7%) FDG/PET CT scans performed at diagnosis were available for review. All patients received steroids given for 21.0 [18.0-28.5] months, associated with methotrexate (n=1, 0.9%) or tocilizumab (n=2, 1.9%). During a median follow-up of 27.5 [11.4-35.0] months, relapse occurred in 40 (37%) patients. Multivariable Cox regression model, including general signs, gender, aortic wall thickness, FDG uptake in arterial wall and IV steroid pulse as covariates, showed that both general signs (HR 2.0 [1.0-4.0, P<0.05) and FDG uptake in limb arteries (HR 2.7 [1.3-5.5], P<0.01) at diagnosis were associated with GCA relapse. CONCLUSION: FDG uptake in limb arteries at diagnosis is a predictor of relapse in newly diagnosed GCA.

Incidence, risk factors and treatment of central nervous system immune reconstitution inflammatory syndrome in non-HIV patients with tuberculous meningitis: a multicentre observational study.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) affecting the central nervous system (CNS) is associated with poor outcomes. AIMS: To report on risk factors for CNS-IRIS following tuberculous meningitis (TBM) in HIV-negative patients. METHODS: In this retrospective multicentre study, all HIV-negative adult patients admitted between 2003 and 2021 with microbiologically proven TBM were included. The primary outcome measure was IRIS onset over follow-up. Characteristics of patients who developed IRIS were described. Factors associated with IRIS were identified using a multivariable logistic regression procedure. RESULTS: Fifty-six patients (33.0 (27.0-44.3) years, 39 (69.6%) men) with microbiologically proven TBM were studied. All patients received antituberculosis treatment and 48 (n = 48/56; 85.7%) steroids at TBM diagnosis. During a median follow-up of 18.0 (12.0-27.3) months, IRIS occurred in 28 (n = 28/56, 50.0%) patients, at a median time of 2.0 (1.0-3.0) months after antituberculosis treatment was started. IRIS involved the CNS in all but one case. Imaging revealed new (n = 23/28, 82.1%) and/or worsening (n = 21/28; 75.0%) of previously recognised lesions. Multivariable analysis showed that meningeal enhancement on brain magnetic resonance imaging (MRI) (odds ratio (OR): 15.3; 95% confidence interval (CI): (1.19-1193.5)) at TBM diagnosis and high blood albumin level (OR: 1.21; 95% CI: (1.02-1.60)) were associated with the occurrence of CNS-IRIS during follow-up. CONCLUSION: CNS-IRIS following TBM in non-HIV patients appears frequent and severe. Meningeal enhancement on brain MRI at tuberculosis diagnosis is a risk factor for CNS-IRIS.

The spectrum of sepsis-associated encephalopathy: a clinical perspective.

Sepsis-associated encephalopathy is a severe neurologic syndrome characterized by a diffuse dysfunction of the brain caused by sepsis. This review provides a concise overview of diagnostic tools and management strategies for SAE at the acute phase and in the long term. Early recognition and diagnosis of SAE are crucial for effective management. Because neurologic evaluation can be confounded by several factors in the intensive care unit setting, a multimodal approach is warranted for diagnosis and management. Diagnostic tools commonly employed include clinical evaluation, metabolic tests, electroencephalography, and neuroimaging in selected cases. The usefulness of blood biomarkers of brain injury for diagnosis remains limited. Clinical evaluation involves assessing the patient's mental status, motor responses, brainstem reflexes, and presence of abnormal movements. Electroencephalography can rule out non-convulsive seizures and help detect several patterns of various severity such as generalized slowing, epileptiform discharges, and triphasic waves. In patients with acute encephalopathy, the diagnostic value of non-contrast computed tomography is limited. In septic patients with persistent encephalopathy, seizures, and/or focal signs, magnetic resonance imaging detects brain injury in more than 50% of cases, mainly cerebrovascular complications, and white matter changes. Timely identification and treatment of the underlying infection are paramount, along with effective control of systemic factors that may contribute to secondary brain injury. Upon admission to the ICU, maintaining appropriate levels of oxygenation, blood pressure, and metabolic balance is crucial. Throughout the ICU stay, it is important to be mindful of the potential neurotoxic effects associated with specific medications like midazolam and cefepime, and to closely monitor patients for non-convulsive seizures. The potential efficacy of targeted neurocritical care during the acute phase in optimizing patient outcomes deserves to be further investigated. Sepsis-associated encephalopathy may lead to permanent neurologic sequelae. Seizures occurring in the acute phase increase the susceptibility to long-term epilepsy. Extended ICU stays and the presence of sepsis-associated encephalopathy are linked to functional disability and neuropsychological sequelae, underscoring the necessity for long-term surveillance in the comprehensive care of septic patients.

Ultrasonography in thoracic and abdominal stab wound injury: results from the FETTHA study.

BACKGROUND: While the role of Extended Focused Assessment with Sonography in Trauma (eFAST) is well defined in the management of severe blunt trauma, its performance in injuries caused by stab wounds has been poorly assessed. METHODS: Prospective single centre study which included all patients with stab wounds to the thorax or abdomen between December 2016 and December 2018. All patients underwent initial investigation with both eFAST and CT scan, except in cases of haemodynamic or respiratory instability, and in cases with a positive diagnosis by eFAST in which case surgery without CT scan was performed. RESULTS: Of the 200 consecutive patients included, 14 unstable patients underwent surgery immediately after eFAST. In these 14 patients, 9 had cardiac tamponade identified by eFAST and all were confirmed by surgery. In the remaining 186 patients, the median time between eFAST and CT scan was 30 min (IQR 20-49 min). Test characteristics (including 95% CI) for eFAST compared with reference standard of CT scan for detecting pneumothorax were as follows: sensitivity 77% (54%-92%), specificity 93% (90%-97%), positive predictive value (PPV) 60% (49%-83%), negative predictive value (NPV) 97% (93%-99%). Test characteristics (including 95% CI) for eFAST compared with CT scan for detecting haemothorax were as follows: sensitivity 97% (74%-99%), specificity 96% (92%-98%), PPV 83% (63%-93%) and NPV 99% (96%-100%). Finally, test characteristics (including 95% CI) for eFAST compared with CT scan for detecting haemoperitoneum were as follows: sensitivity 75% (35%-97%), specificity 97% (93%-99%), PPV 55% (23%-83%) and NPV 99% (96%-99%). CONCLUSIONS: In patients admitted with stab wounds to the torso, eFAST was not sensitive enough to diagnose pneumothorax and haemoperitoneum, but performed better in the detection of cardiac tamponade and haemothorax than the other injuries. More robust multicentre studies are needed to better define the role of eFAST in this specific population.

Bypass grafting to the third segment of the vertebral artery for symptomatic extensive vertebrobasilar atherosclerotic disease.

Symptomatic vertebrobasilar atherosclerotic disease is rarely encountered but represents a high-risk factor for recurrent transient ischemic attack or stroke. Posterior strokes are usually associated with embolism or hemodynamic impairment. Extensive disease involving the V3 and V4 segments of the vertebral artery (VA) remains infrequent, and optimal management is limited owing to the infrequency of this disease. We illustrate the case of a 65-year-old man who presented with recurrent transient episodes of dizziness with acute onset of instability, nausea, and left visual blurring. Magnetic resonance imaging findings of the head were normal, and computed tomography angiography revealed severe atherosclerotic disease of both VAs, with proximal occlusion of the right VA and multiple tight stenoses of the left VA at the V1 and V4 segments. Duplex ultrasound found markedly reduced anterograde flow in the VAs and basilar arteries and nonsignificant stenosis of the internal carotid arteries. Optimal medical treatment led to a decrease of transient symptoms. However, the patient developed a cerebellar infarction in the left posteroinferior cerebellar artery territory with left VA V4 segment occlusion. Surgical revascularization of the right VA was decided by the multidisciplinary team. Through an anterolateral approach of the right VA V3 segment, revascularization was performed using a common carotid artery-to-right VA bypass using a reversed saphenous vein graft. The patient fully recovered and was free of symptoms during the next 14 months of follow-up. In the case of extensive VA occlusive disease, surgical reconstruction of the distal VA using a bypass from the common carotid artery represents an option to improve hemodynamics and/or eliminate an embolic source of posterior stroke on a case-by-case basis.

Who publishes imaging articles in non-imaging journals? A large sample data-mining study.

OBJECTIVES: To assess the weight of imaging and imaging specialists (i.e., affiliated to a radiology/nuclear medicine department) in publications in non-imaging journals. METHODS: All articles indexed in English on the Embase database between 1989 and 2019 were extracted. The number and affiliation of authors were determined. A naive Bayesian classifier algorithm was trained to classify abstracts as "imaging" or "non-imaging." The main outcome was the number and position of imaging specialists in the authorship of imaging articles published in non-imaging journals. Analyses per medical specialties and per journal impact factor (IF) were performed. RESULTS: A total of 15,787,825 articles were included with 968,259 (6%) "imaging" articles. The proportion of imaging articles increased over time (+ 370%), quicker than the overall academic output. The proportion of imaging specialist among authors grew from 0.58% in 1989-1994 to 1.54% in 2015-2019. About 20% of imaging articles had ≥ 1 imaging specialist among authors. The proportion of imaging articles decreased with the IF (7.3% for IF 0-2.5 vs. 5.1% for IF > 10, p < 0.001), but the proportion of imaging specialist authors in imaging papers with ≥ 1 imaging specialist author increased with the IF (40% for IF 0-2.5, 53% for IF > 10, p < 0.001). There was significant variability across medical specialties. CONCLUSIONS: The weight of imaging articles and imaging specialist among authors in non-imaging journals has increased over time but remains limited. Most of the authors of imaging publications are not imaging specialists. Imaging specialists among authors in imaging papers are associated with a greater IF. KEY POINTS: • The proportion of imaging specialist authors in non-imaging journals, though small, has increased significantly. • Marked differences are observed according to medical specialties and the reputation/impact factor of the journal. • Collaboration between imaging specialists and non-specialists is associated with publication in higher impact journals.

Cerebral perfusion using ASL in patients with COVID-19 and neurological manifestations: A retrospective multicenter observational study.

BACKGROUND AND PURPOSE: Cerebral hypoperfusion has been reported in patients with COVID-19 and neurological manifestations in small cohorts. We aimed to systematically assess changes in cerebral perfusion in a cohort of 59 of these patients, with or without abnormalities on morphological MRI sequences. METHODS: Patients with biologically-confirmed COVID-19 and neurological manifestations undergoing a brain MRI with technically adequate arterial spin labeling (ASL) perfusion were included in this retrospective multicenter study. ASL maps were jointly reviewed by two readers blinded to clinical data. They assessed abnormal perfusion in four regions of interest in each brain hemisphere: frontal lobe, parietal lobe, posterior temporal lobe, and temporal pole extended to the amygdalo-hippocampal complex. RESULTS: Fifty-nine patients (44 men (75%), mean age 61.2 years) were included. Most patients had a severe COVID-19, 57 (97%) needed oxygen therapy and 43 (73%) were hospitalized in intensive care unit at the time of MRI. Morphological brain MRI was abnormal in 44 (75%) patients. ASL perfusion was abnormal in 53 (90%) patients, and particularly in all patients with normal morphological MRI. Hypoperfusion occurred in 48 (81%) patients, mostly in temporal poles (52 (44%)) and frontal lobes (40 (34%)). Hyperperfusion occurred in 9 (15%) patients and was closely associated with post-contrast FLAIR leptomeningeal enhancement (100% [66.4%-100%] of hyperperfusion with enhancement versus 28.6% [16.6%-43.2%] without, p = 0.002). Studied clinical parameters (especially sedation) and other morphological MRI anomalies had no significant impact on perfusion anomalies. CONCLUSION: Brain ASL perfusion showed hypoperfusion in more than 80% of patients with severe COVID-19, with or without visible lesion on conventional MRI abnormalities.

Cerebrovascular complications and outcomes of critically ill adult patients with infective endocarditis.

BACKGROUND: Neurological complications are associated with poor outcome in patients with infective endocarditis (IE). Although guidelines recommend systematic brain imaging in the evaluation of IE patients, the association between early brain imaging findings and outcomes has never been evaluated in critically ill patients. We aimed to assess the association of CT-defined neurological complications with functional outcomes of critically ill IE patients. METHODS: This retrospective cohort study included consecutive patients with severe, left-sided IE hospitalized in the medical ICU of a tertiary care hospital. Patients with no baseline brain CT were excluded. Baseline CT-scans were classified in five mutually exclusive categories (normal, moderate-to-severe ischemic stroke, minor ischemic stroke, intracranial hemorrhage, other abnormal CT). The primary endpoint was 1-year favorable outcome, defined by a modified Rankin Scale score of 0-3. RESULTS: Between 06/01/2011 and 07/31/2018, 156 patients were included. Among them, 87/156 (56%) had a CT-defined neurological complication, including moderate-to-severe ischemic stroke (n = 33/156, 21%), intracranial hemorrhage (n = 24/156, 15%), minor ischemic stroke (n = 29/156, 19%), other (n = 3/156, 2%). At one year, 69 (45%) patients had a favorable outcome. Factors negatively associated with favorable outcome in multivariable analysis were moderate-to-severe ischemic stroke (OR 0.37, 95%CI 0.14 - 0.95) and age (OR 0.94, 95%CI 0.91-0.97). By contrast, the score on the Glasgow Coma Scale was positively associated with favorable outcome (per 1-point increment, OR 1.23, 95%CI 1.08-1.42). Sensitivity analyses conducted in operated patients revealed similar findings. Compared to normal CT, only moderate-to-severe ischemic stroke was associated with more frequent post-operative neurological complications (n = 8/23 (35%) vs n = 1/46 (2%), p < 0.01). CONCLUSION: Moderate-to-severe ischemic stroke had an independent negative impact on 1-year functional outcome in critically ill IE patients; whereas other complications, including intracranial hemorrhage, had no such impact.

Critical care management of meningitis and encephalitis: an update.

PURPOSE OF REVIEW: Meningitis and encephalitis represent severe neurological syndromes associated with encephalopathy, seizures, focal deficits, and neurological sequelae in survivors. We update on the critical care management of adult patients with severe meningitis and encephalitis. RECENT FINDINGS: Large multicenter studies conducted in the adult population improved current knowledge on the epidemiology and outcomes of patients with severe meningitis and encephalitis. An early multimodal diagnostic workup (including CSF analysis, brain MRI, EEG, and serum studies) is mandatory for diagnosis and prognostication in those patients.New diagnostic methods, including multiplex PCR and next-generation sequencing techniques, allow for a faster differential diagnosis of infectious causes that may require specific antimicrobial therapy. Autoimmune causes of encephalitis, which may require urgent immunotherapy, are also increasingly recognized in the ICU setting. Although observational data suggest that early combined immunotherapy is associated with better neurological outcomes in patients with autoimmune encephalitis, randomized clinical trials have yet to be performed. SUMMARY: Our review highlights the importance of an early multimodal approach for diagnosing severe meningitis and encephalitis. Randomized clinical trials are needed to identify pharmacological interventions that may improve patients' outcomes.

Brain abscess in immunocompetent patients: recent findings.

PURPOSE OF REVIEW: We conducted a systematic review of the literature to update findings on the epidemiology and the management of cerebral abscesses in immunocompetent patients. RECENT FINDINGS: Observational studies suggest that the overall prognosis has improved over the last decades but mortality rates remain high. Several parameters may contribute to a better prognosis, including the identification of common risk factors for brain abscess, the systematic use of brain MRI at diagnosis, the implementation of appropriate neurosurgical and microbiological techniques for diagnosis, the optimization of the antibacterial treatment based on epidemiology and pharmacokinetic/pharmacodynamic studies, and a long-term follow-up for detection of secondary complications. Outcome research on brain abscess is mainly based on observational studies. Randomized controlled trials have yet to be performed to identify clinically relevant interventions associated with improved patient-centered outcomes. SUMMARY: Our review highlights the importance of a multidisciplinary approach to optimize brain abscess management both at the acute phase and in the long-term. Randomized controlled studies are urgently needed to identify interventions associated with improved outcomes.

Prone-Positioning for Severe Acute Respiratory Distress Syndrome Requiring Extracorporeal Membrane Oxygenation.

OBJECTIVES: To determine the characteristics and outcomes of patients prone-positioned during extracorporeal membrane oxygenation for severe acute respiratory distress syndrome and lung CT pattern associated with improved respiratory system static compliance after that intervention. DESIGN: Retrospective, single-center study over 8 years. SETTINGS: Twenty-six bed ICU in a tertiary center. MEASUREMENTS AND MAIN RESULTS: A propensity score-matched analysis compared patients with prone-positioning during extracorporeal membrane oxygenation and those without. An increase of the static compliance greater than or equal to 3 mL/cm H2O after 16 hours of prone-positioning defined prone-positioning responders. The primary outcome was the time to successful extracorporeal membrane oxygenation weaning within 90 days of postextracorporeal membrane oxygenation start, with death as a competing risk. Among 298 venovenous extracorporeal membrane oxygenation-treated adults with severe acute respiratory distress syndrome, 64 were prone-positioning extracorporeal membrane oxygenation. Although both propensity score-matched groups had similar extracorporeal membrane oxygenation durations, prone-positioning extracorporeal membrane oxygenation patients' 90-day probability of being weaned-off extracorporeal membrane oxygenation and alive was higher (0.75 vs 0.54, p = 0.03; subdistribution hazard ratio [95% CI], 1.54 [1.05-2.58]) and 90-day mortality was lower (20% vs 42%, p < 0.01) than that for no prone-positioning extracorporeal membrane oxygenation patients. Extracorporeal membrane oxygenation-related complications were comparable for the two groups. Patients without improved static compliance had higher percentages of nonaerated or poorly aerated ventral and medial-ventral lung regions (p = 0.047). CONCLUSIONS: Prone-positioning during venovenous extracorporeal membrane oxygenation was safe and effective and was associated with a higher probability of surviving and being weaned-off extracorporeal membrane oxygenation at 90 days. Patients with greater normally aerated lung tissue in the ventral and medial-ventral regions on quantitative lung CT-scan performed before prone-positioning are more likely to improve their static compliance after that procedure during extracorporeal membrane oxygenation.

Neurologic and neuroimaging findings in patients with COVID-19: A retrospective multicenter study.

OBJECTIVE: To describe neuroimaging findings and to report the epidemiologic and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with neurologic manifestations. METHODS: In this retrospective multicenter study (11 hospitals), we included 64 patients with confirmed COVID-19 with neurologic manifestations who underwent a brain MRI. RESULTS: The cohort included 43 men (67%) and 21 women (33%); their median age was 66 (range 20-92) years. Thirty-six (56%) brain MRIs were considered abnormal, possibly related to severe acute respiratory syndrome coronavirus. Ischemic strokes (27%), leptomeningeal enhancement (17%), and encephalitis (13%) were the most frequent neuroimaging findings. Confusion (53%) was the most common neurologic manifestation, followed by impaired consciousness (39%), presence of clinical signs of corticospinal tract involvement (31%), agitation (31%), and headache (16%). The profile of patients experiencing ischemic stroke was different from that of other patients with abnormal brain imaging: the former less frequently had acute respiratory distress syndrome (p = 0.006) and more frequently had corticospinal tract signs (p = 0.02). Patients with encephalitis were younger (p = 0.007), whereas agitation was more frequent for patients with leptomeningeal enhancement (p = 0.009). CONCLUSIONS: Patients with COVID-19 may develop a wide range of neurologic symptoms, which can be associated with severe and fatal complications such as ischemic stroke or encephalitis. In terms of meningoencephalitis involvement, even if a direct effect of the virus cannot be excluded, the pathophysiology seems to involve an immune or inflammatory process given the presence of signs of inflammation in both CSF and neuroimaging but the lack of virus in CSF. CLINICALTRIALSGOV IDENTIFIER: NCT04368390.

Brain MRI Findings in Severe COVID-19: A Retrospective Observational Study.

Background Brain MRI parenchymal signal abnormalities have been associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Purpose To describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe coronavirus disease 2019 (COVID-19) infection. Materials and Methods This was a retrospective study of patients evaluated from March 23, 2020, to April 27, 2020, at 16 hospitals. Inclusion criteria were (a) positive nasopharyngeal or lower respiratory tract reverse transcriptase polymerase chain reaction assays, (b) severe COVID-19 infection defined as a requirement for hospitalization and oxygen therapy, (c) neurologic manifestations, and (d) abnormal brain MRI findings. Exclusion criteria were patients with missing or noncontributory data regarding brain MRI or brain MRI showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. Categorical data were compared using the Fisher exact test. Quantitative data were compared using the Student t test or Wilcoxon test. P < .05 represented a significant difference. Results Thirty men (81%) and seven women (19%) met the inclusion criteria, with a mean age of 61 years ± 12 (standard deviation) (age range, 8-78 years). The most common neurologic manifestations were alteration of consciousness (27 of 37, 73%), abnormal wakefulness when sedation was stopped (15 of 37, 41%), confusion (12 of 37, 32%), and agitation (seven of 37, 19%). The most frequent MRI findings were signal abnormalities located in the medial temporal lobe in 16 of 37 patients (43%; 95% confidence interval [CI]: 27%, 59%), nonconfluent multifocal white matter hyperintense lesions seen with fluid-attenuated inversion recovery and diffusion-weighted sequences with variable enhancement, with associated hemorrhagic lesions in 11 of 37 patients (30%; 95% CI: 15%, 45%), and extensive and isolated white matter microhemorrhages in nine of 37 patients (24%; 95% CI: 10%, 38%). A majority of patients (20 of 37, 54%) had intracerebral hemorrhagic lesions with a more severe clinical presentation and a higher admission rate in intensive care units (20 of 20 patients [100%] vs 12 of 17 patients without hemorrhage [71%], P = .01) and development of the acute respiratory distress syndrome (20 of 20 patients [100%] vs 11 of 17 patients [65%], P = .005). Only one patient had SARS-CoV-2 RNA in the cerebrospinal fluid. Conclusion Patients with severe coronavirus disease 2019 and without ischemic infarcts had a wide range of neurologic manifestations that were associated with abnormal brain MRI scans. Eight distinctive neuroradiologic patterns were described. © RSNA, 2020.