Pro-inflammatory cerebrospinal fluid profile of neonates with intraventricular hemorrhage: clinical relevance and contrast with CNS infection.

BACKGROUND: Interpretation of cerebrospinal fluid (CSF) studies can be challenging in preterm infants. We hypothesized that intraventricular hemorrhage (IVH), post-hemorrhagic hydrocephalus (PHH), and infection (meningitis) promote pro-inflammatory CSF conditions reflected in CSF parameters. METHODS: Biochemical and cytological profiles of lumbar CSF and peripheral blood samples were analyzed for 81 control, 29 IVH grade 1/2 (IVH1/2), 13 IVH grade 3/4 (IVH3/4), 15 PHH, 20 culture-confirmed bacterial meningitis (BM), and 27 viral meningitis (VM) infants at 36.5 ± 4 weeks estimated gestational age. RESULTS: PHH infants had higher (p < 0.02) CSF total cell and red blood cell (RBC) counts compared to control, IVH1/2, BM, and VM infants. No differences in white blood cell (WBC) count were found between IVH3/4, PHH, BM, and VM infants. CSF neutrophil counts increased (p ≤ 0.03) for all groups compared to controls except IVH1/2. CSF protein levels were higher (p ≤ 0.02) and CSF glucose levels were lower (p ≤ 0.003) for PHH infants compared to all other groups. In peripheral blood, PHH infants had higher (p ≤ 0.001) WBC counts and lower (p ≤ 0.03) hemoglobin and hematocrit than all groups except for IVH3/4. CONCLUSIONS: Similarities in CSF parameters may reflect common pathological processes in the inflammatory response and show the complexity associated with interpreting CSF profiles, especially in PHH and meningitis/ventriculitis.

Nanopore targeted sequencing-based diagnosis of central nervous system infections in HIV-infected patients.

BACKGROUND: Early and accurate etiological diagnosis is very important for improving the prognosis of central nervous system (CNS) infections in human immunodeficiency virus (HIV)-infected patients. The goal is not easily achieved by conventional microbiological tests. We developed a nanopore targeted sequencing (NTS) platform and evaluated the diagnostic performance for CNS infections in HIV-infected patients, with special focus on cryptococcal meningitis (CM). We compared the CM diagnostic performance of NTS with conventional methods and cryptococcal polymerase chain reaction (PCR). METHODS: This study included 57 hospitalized HIV-infected patients with suspected CNS infections from September 2018 to March 2022. The diagnosis established during hospitalization includes 27 cases of CM, 13 CNS tuberculosis, 5 toxoplasma encephalitis, 2 cytomegalovirus (CMV) encephalitis and 1 Varicella-zoster virus (VZV) encephalitis. The 2 cases of CMV encephalitis also have co-existing CM. Target-specific PCR amplification was used to enrich pathogen sequences before nanopore sequencing. NTS was performed on stored cerebrospinal fluid (CSF) samples and the results were compared with the diagnosis during hospitalization. RESULTS: 53 (93.0%) of the patients were male. The median CD4 cell count was 25.0 (IQR: 14.0-63.0) cells/uL. The sensitivities of CSF culture, India ink staining, cryptococcal PCR and NTS for CM were 70.4% (95%CI: 51.5 - 84.1%), 76.0% (95%CI: 56.6 - 88.5%), 77.8% (59.2 - 89.4%) and 85.2% (95%CI: 67.5 - 94.1%), respectively. All those methods had 100% specificity for CM. Our NTS platform could identify Cryptococcus at species level. Moreover, NTS was also able to identify all the 5 cases of toxoplasma encephalitis, 2 cases of CMV encephalitis and 1 VZV encephalitis. However, only 1 of 13 CNS tuberculosis cases was diagnosed by NTS, and so did Xpert MTB/RIF assay. CONCLUSIONS: NTS has a good diagnostic performance for CM in HIV-infected patients and may have the ability of simultaneously detecting other pathogens, including mixed infections. With continuing improving of the NTS platform, it may be a promising alterative microbiological test for assisting with the diagnosis of CNS infections.

Characterizing Epstein-Barr virus infection of the central nervous system in Zambian adults living with HIV.

The significance of Epstein-Barr virus (EBV) detection in the cerebrospinal spinal fluid (CSF) in people living with HIV (PLWH) is not entirely understood. The detection of EBV DNA may represent active central nervous system (CNS) infection, reactivation in the setting of another CNS pathogen or due to impaired immunity, or detection of quiescent virus. We screened 470 adult PLWH in Zambia with neurological symptoms for the presence of EBV DNA in the CSF. We performed quantitative EBV PCR on the CSF and blood. We then performed quantitative EBV DNA PCR on the blood of controls with documented HIV viral suppression without CNS symptoms. The prevalence of EBV DNA in the CSF of patients with CNS symptoms was 28.9% (136/470). EBV DNA positivity was associated with younger age, shorter duration of HIV diagnosis, lower CSF glucose levels, higher CSF protein and white blood cell levels, and a positive CSF Mycobacterium tuberculosis result. The median EBV DNA load was 8000 cps/mL in both the CSF and blood with a range of 2000-2,753,000 cps/mL in the CSF and 1000 to 1,871,000 cps/mL in the blood. Molecular screening of CSF for other possible causes of infection identified Mycobacterium tuberculosis in 30.1% and cytomegalovirus (CMV) in 10.5% of samples. EBV DNA load in the blood and CSF was not associated with mortality. Our results suggest that even though EBV DNA was commonly detected in the CSF of our population, it appears to have limited clinical significance regardless of EBV DNA load.

Human parechovirus meningitis in children: state of the art.

Human Parechovirus is a common cause of infection occurring especially during the first years of life. It may present with a broad spectrum of manifestations, ranging from a pauci-symptomatic infection to a sepsis-like or central nervous system disease. Aim of this study is to explore the knowledge on Parechovirus meningitis. According to the purpose of the study, a systematic review of the literature focusing on reports on central nervous system. Parechovirus infection of children was performed following PRISMA criteria. Out of the search, 304 papers were identified and 81 records were included in the revision dealing with epidemiology, clinical manifestations, laboratory findings, imaging, therapy and outcome. Parechovirus meningitis incidence may vary all over the world and outbreaks may occur. Fever is the most common symptom, followed by other non-specific signs and symptoms including irritability, poor feeding, skin rash or seizures. Although several reports describe favourable short-term neurodevelopmental outcomes at discharge after Parechovirus central nervous system infection, a specific follow up and the awareness on the risk of sequelae should be underlined in relation to the reported negative outcome. Evidence seems to suggest a correlation between magnetic imaging resonance alteration and a poor outcome.

Spontaneous Clostridium perfringens Meningitis and Brain Abscess in a Neonate.

This case describes a neonate who presented with spontaneous Clostridium perfringens meningitis and brain abscess. The abscess was drained, and the infant completed a 6-week course of antibiotics. Throughout this time the infant remained well with no need for intensive care. C. perfringens central nervous system infections are associated with trauma and poor outcomes. This case highlights that the spectrum of disease can include spontaneous infection with a relatively mildly clinical course demonstrating the importance of 16s polymerase chain reaction in culture-negative cases and its role in detecting rare causes of central nervous system infections such as C. perfringens .

Brain MRI features of anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis secondary to central nervous system infection in adult patients.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis secondary to central nervous system (CNS) infection is a unique subtype of the autoimmune-mediated disease, of which the imaging features are unclear. PURPOSE: To compare the brain magnetic resonance imaging (MRI) features between the anti-NMDAR encephalitis secondary to CNS infection and that without initial infection. MATERIAL AND METHODS: A total of 70 adult patients with anti-NMDAR encephalitis were retrospectively enrolled (24 in the post-infection group, 46 in the non-infection-related group). Their clinical and imaging features (lesion distribution, lesion shape, enhancement pattern, brain atrophy) were reviewed and summarized. Lesion distributions were compared between the two groups on lesion probability maps. RESULTS: The patients with normal brain MRI scans in the post-infection group were less than those in the non-infection related group (29% vs. 63%; P = 0.0113). Among the 24 patients in the post-infection group, visible lesions were shown at the anti-NMDAR encephalitis onset in 17 patients; lesion distribution was more diffuse than the non-infection-related group, showing higher lesion peak probabilities in the bilateral hippocampus, frontal lobe, temporal lobe, insula, and cingulate. The lesions with contrast enhancement were also more common in the post-infection group than the non-infection-related group (7/13 vs. 2/10). Brain atrophy was observed in eight patients in the post-infection group and three in the non-infection-related group. CONCLUSION: Anti-NMDAR encephalitis secondary to CNS infection has its imaging features-extensive lesion distribution, leptomeningeal enhancement, early atrophy, and necrosis-that could deepen the understanding of the pathophysiology and manifestation of the autoimmune encephalitis besides the classic type.

Epidemiology and Disease Burden of Hospitalized Children With Viral Central Nervous System Infections in China, 2016 to 2020.

BACKGROUND: Viral central nervous system (CNS) infections seriously threaten the life and health of children, with a high mortality and severe sequelae in China and globally. Surveillance of viral CNS infections in children is important, especially in hospitalized children, to facilitate disease evaluation. METHODS: In this study, we collected the data on the discharged Face Sheet of Medical Records from database from 2016 to 2020 and analyzed the epidemiologic characteristics and disease burden of hospitalized children (≤18 years old) with viral CNS infections in China. We classified the discharge diagnosis of viral CNS infection as viral encephalitis (VE), viral meningitis (VM), viral meningoencephalitis (VME), viral encephalomyelitis (VEM), and viral meningomyelitis (VMM). RESULTS: A total of 42,641 cases of viral CNS infections were included in the database, consisting of 39,279 cases with VE (92.47%), 2011 cases with VM (4.73%), 1189 cases with VME (2.80%), 118 cases with VEM (0.28%), and 44 cases with VMM (0.10%). The number of hospitalized patients with viral CNS infections accounted for 0.74% (42,641 of 5,790,910) of all hospitalized cases. The onset of viral CNS infections presented seasonal characteristic, with peaks in June to July and December to January. Seizures are the most frequent complication of this disorder. Median length of stay and inpatient expenditures for patients with viral CNS infections were 9 days and 1144.36 USD. Causative viruses were identified in 4.33% (1848 of 42,641) of patients. CONCLUSIONS: This study will help understand the clinical epidemiology and disease burden of hospitalized children with viral CNS infections in China.

Seizures in adults with suspected central nervous system infection.

BACKGROUND: Seizures can be part of the clinical presentation of central nervous system (CNS) infections. We describe patients suspected of a neurological infection who present with a seizure and study diagnostic accuracy of clinical and laboratory features predictive of CNS infection in this population. METHODS: We analyzed all consecutive patients presenting with a seizure from two prospective Dutch cohort studies, in which patients were included who underwent cerebrospinal fluid (CSF) examination because of the suspicion of a CNS infection. RESULTS: Of 900 episodes of suspected CNS infection, 124 (14%) presented with a seizure. The median age in these 124 episodes was 60 years (IQR 45-71) and 53% of patients was female. CSF examination showed a leukocyte count ≥ 5/mm3 in 41% of episodes. A CNS infection was diagnosed in 27 of 124 episodes (22%), a CNS inflammatory disorder in 8 (6%) episodes, a systemic infection in 10 (8%), other neurological disease in 77 (62%) and in 2 (2%) episodes another systemic disease was diagnosed. Diagnostic accuracy of clinical and laboratory characteristics for the diagnosis of CNS infection in this population was low. CSF leukocyte count was the best predictor for CNS infection in patients with suspected CNS infection presenting with a seizure (area under the curve 0.94, [95% CI 0.88 - 1.00]). CONCLUSIONS: Clinical and laboratory features fail to distinguish CNS infections from other causes of seizures in patients with a suspected CNS infection. CSF leukocyte count is the best predictor for the diagnosis of CNS infection in this population.

The clinical analysis of new-onset status epilepticus.

OBJECTIVE: To investigate and analyze the etiology and prognosis of patients with new-onset status epilepticus (NOSE). METHODS: We conducted a retrospective analysis of all adult patients (≧16 years old) who were admitted to Sichuan Provincial People's Hospital between January 2018 and December 2020 with status epilepticus (SE) and no prior epilepsy history. RESULTS: We collected data from 85 patients, aged from 16 to 90 years, of whom 49 were male and 36 were female. Fifty-five of these cases (64.7%) were younger than 60 years of age. Acute symptomatic SE was mostly seen in the NOSE (53.9%), followed by unknown SE (25.9%), progressive SE (11.8%), and remote SE (9.4%). The differences in the etiology of NOSE between age groups were statistically significant (P < .05). For the young, the main etiology remained unknown (36.3%), followed by autoimmune-related SE (16.4%); in the elderly, the primary etiology was central nervous system (CNS) infection (23.3%), followed by cerebrovascular disease (20%), and intracranial tumors (20%). Normal imaging was mostly seen in young people with NOSE (P < .001). Regarding outcome parameters and risk factors in patients with NOSE, adverse outcome was associated with age (OR = 3.5, 95% CI = 0.108-0.758, P = .012), co-infection (OR = 4.5, 95% CI = 0.083-0.599, P = .003), and tracheal intubation (OR = 6.318, 95% CI = 0.060-0.204, P = .011). SIGNIFICANCE: In our cohort, intracranial tumors, CNS infections, and cerebrovascular disease were the predominant causes of NOSE in the elderly, while autoimmune encephalitis was the largest recognized cause of NOSE in young patients. In addition, imaging varies with age. According to the data, preventing infections may enhance patient prognosis because greater infection rates are connected with less favorable results. Meanwhile, age and mechanical ventilation are related to the prognosis of NOSE.

[Central nervous system infections and targeted therapies: what to consider]. / Infections du système nerveux central et thérapies ciblées : à quoi faut-il penser ?

The development of targeted therapies has revolutionized the approach to immunosuppression in several medical specialties. While the prescriber of these therapies is familiar with these agents, both the general internist and the infectious disease specialist must deal with the consequences of these products. Encephalitis, for which prompt and appropriate management is paramount, is a challenge in the patient undergoing immunomodulatory therapies because of its atypical presentation, the involvement of particular germs and the potential brain toxicity of some immunomodulatory treatments. This article outlines the mechanisms of action of some targeted therapies and reviews the associated brain infections.

Le développement des thérapies ciblées a révolutionné l'approche de l'immunosuppression dans plusieurs spécialités médicales. Si le prescripteur de ces thérapies est familiarisé avec ces agents, l'interniste généraliste et l'infectiologue doivent tous deux faire face aux conséquences de ces produits. Les encéphalites, dont la prise en charge rapide et adéquate est primordiale, représentent un défi chez le patient soumis aux thérapies immunomodulatrices, en raison de leur présentation atypique, de l'implication de germes particuliers et de la toxicité cérébrale potentielle de certains traitements immunomodulateurs. Cet article expose les mécanismes d'action de certaines thérapies ciblées et passe en revue les infections de l'encéphale qui y sont associées.

Cerebrospinal fluid analysis: current diagnostic methods in central nervous system infectious diseases.

Cerebrospinal fluid (CSF) analysis is an important diagnostic tool for many conditions affecting the central nervous system (CNS), especially CNS infectious diseases. Despite its low specificity, CSF white blood cell counts, CSF protein levels, CSF serum glucose ratio and CSF lactate measurement are useful in differentiating infections caused by distinct groups of pathogens. CSF direct examination and cultures can identify causative organisms and antibiotic sensitivities as well. Adjunctive tests such as latex agglutination, different immunological assays and molecular reactions have great specificities and increasing sensitivities. In this article, some recent diagnostic methods applied to CSF analysis for frequent CNS infections are presented.

Treatment of Capnocytophaga sputigena meningitis in a neurosurgical patient.

A woman in her 50s developed meningitis following an endoscopic, endonasal resection of a clival meningioma which was complicated by a cerebrospinal fluid (CSF) leak through the nose. CSF analysis showed a raised white cell count, and Capnocytophaga sputigena was isolated. This organism is an oral commensal and is implicated in periodontal disease; the CSF leak explains the portal of entry. C. sputigena is rarely isolated, and this is the first report of a central nervous system (CNS) infection caused by this organism. A worsening of our patient's dermatological condition, urticaria pigmentosa, coincided with empiric treatment with vancomycin and meropenem, which were therefore discontinued. Treatment was continued with chloramphenicol for 3 weeks, and the patient made a full recovery. Systemic chloramphenicol is uncommonly used in contemporary UK practice, but remains an excellent antibiotic for CNS penetration and it has excellent bioavailability. We anticipate increased chloramphenicol use as the number of multiresistant Gram-negative infection increases.

Neurodevelopmental outcomes of newborns and infants with parechovirus and enterovirus central nervous infection: a 5-year longitudinal study.

Though parechovirus (PeV) and enterovirus (EV) are common causes of central nervous system (CNS) infection in childhood, little is known about their long-term neurologic/neurodevelopmental complications. We investigated, longitudinally over a 5-year period, motor neurodevelopment in term-born newborns and infants with RT-qPCR-confirmed PeV- or EV-CNS infection. Motor neurodevelopment was assessed with standardized tests: Alberta Infant Motor Scale (AIMS), Bayley Scales of Infant and Toddler Development version-3 (Bayley-3-NL), and Movement Assessment Battery for Children version-2 (M-ABC-2-NL) at 6, 12, 24, and 60 months post-infection. Results of children with PeV-CNS infection were compared with those of peers with EV-CNS infection and with Dutch norm references. In the multivariate analyses adjustments were made for age at onset, gender, maternal education, and time from CNS infection Sixty of 172 eligible children aged ≤ 3 months were included. Children with PeV-CNS infection had consistently lower, non-significant mean gross motor function (GMF) Z-scores, compared with peers with EV-CNS infection and population norm-referenced GMF. Their GMF improved between 6 and 24 months and decreased at 5 years. Their fine motor function (FMF) scores fell within the population norm reference. CONCLUSION: These results suggest that the impact of PeV-A3-CNS infection on gross motor neurodevelopment in young children might manifest later in life. They highlight the importance of longitudinal neurodevelopmental assessments of children with PeV-A3-CNS infection up to school age. WHAT IS KNOWN: • Human parechovirus (PeV) is a major cause of central nervous system infection (CNS infection) in newborns and infants. • There is interest in the neurological and neurodevelopmental outcome of newborns and infants with PeV-A3-CNS infection. WHAT IS NEW: • This prospective study compares the motor neurodevelopment of term-born newborns and infants with PeV-A3-CNS infection with those with EV-CNS infection and with norm references. • The results support the importance of follow-up of newborns and infants with PeV-A3-CNS infection to detect subtle neurodevelopmental delay and start early interventions.

Diagnostic criteria of CNS infection in patients with external ventricular drainage after traumatic brain injury: a pilot study.

BACKGROUND: Ventriculostomy-related infection (VRI) is a common complication in patients with traumatic brain injury (TBI) treated with an external ventricular drain (EVD). The aim of this study was to investigate incidence and characteristics of patients with VRI, and to explore diagnostic criteria to confidently rule out VRI in patients with TBI. METHODS: This retrospective cohort pilot study included adults with severe TBI who were admitted to the ICU and received an EVD, during a 26-month period. Patients were categorized as having Culture-positive VRI, Culture-negative VRI, or No VRI. Variables that were potentially associated with Culture-positive VRI was analyzed, and predictive values were calculated. RESULTS: 75 of 215 patients with severe TBI (35%) underwent EVD placement; nine of these (12%) were classified as Culture-negative VRI and eight (11%) as Culture-positive VRI. The CSF cell counts that led to VRI treatment were compared with 46 CSF cell counts from No VRI patients. A CSF/plasma glucose ratio below 0.6 had a negative predictive value (NPV) for culture-verified VRI of 0.97 (95% CI: 0.85-1), whereas a combination of three CSF-derived biomarkers within the reference limits (white/red blood cell ratio, CSF/plasma glucose ratio, and protein content) ruled out Culture-positive VRI in this cohort (PPV 0, 95% CI: 0-0.14). C-reactive protein did not reliably predict VRI. CONCLUSIONS: In this pilot study of patients after severe, a combination of biomarkers within reference limits ruled out VRI (PPV 0, CI: 0-0.14). Hypoglycorrhachia was a sensitive marker of VRI (NPV 0.97, CI: 0.85-1). Systemic signs and markers of infection did not predict VRI.

Risks of central nervous system infections and related mortality in patients undergoing dialysis.

INTRODUCTION: This study aimed to investigate the risks of central nervous system (CNS) infections and related mortality in patients with end-stage renal disease (ESRD) undergoing dialysis. METHODS: Incident dialysis patients were identified from 2000 to 2013. The risks of CNS infection and related mortality were analyzed. RESULTS: The adjusted hazard ratio (HR) of CNS infection in the ESRD group compared with the control group was 3.46 (95% confidence interval [CI] 2.75-4.35). The adjusted odds ratio (OR) of 90-day mortality following CNS infections in the ESRD group in comparison with the control group was 5.99 (95% CI 2.78-12.9). The adjusted HR of overall CNS infection for the peritoneal dialysis (PD) group in comparison with the hemodialysis (HD) group was 1.07 (95% CI 0.63-1.82). Influenza vaccination was associated with a lower risks of CNS infection in dialysis patients (adjusted HR: 0.38, 95% CI 0.30-0.48). The adjusted OR of 90-day mortality following CNS infection for the PD group in comparison with the HD group was 1.01 (95% CI 0.55-1.87). CONCLUSIONS: The risks of CNS infections and related mortality were remarkably high in dialysis patients with no significant difference between patients with ESRD under HD and PD treatment.

Central nervous system infections in patients with systemic lupus erythematosus: a systematic review and meta-analysis.

We aimed to conduct a systematic review and meta-analysis of studies on central nervous system (CNS) infections in patients with SLE, in order to describe their clinical and microbiological characteristics, and outcomes. A systematic search of PubMed/Medline and Embase electronic databases was performed (March 2021) to identify all published studies on CNS infections and their characteristics in patients with SLE. A random-effects model was adopted and findings were reported with 95% CI. Overall, 6 studies involving 17 751 patients with SLE and 209 SLE cases with CNS infection were included in our meta-analysis. The frequency rate of CNS infections in patients with SLE was 0.012 (95% CI: 0.008 to 0.018). Meningitis was the most common clinical syndrome (93.5%, n=109/114, 95% CI: 82.6% to 97.8%) and Cryptococcus neoformans (35.9%, n=55, 95% CI: 27.2% to 45.7%) and Mycobacterium tuberculosis (27.1%, n=43, 95% CI: 14.6% to 44.8%) were the most common causative pathogens. Our patient-pool showed a mean SLE Disease Activity Index (SLEDAI) score of 7.9 (95% CI: 6.1 to 9.6), while 92.4% (n=72/76, 95% CI: 83.0% to 96.8%) of cases were on oral systemic corticosteroids, with a prednisone equivalent mean daily dose of 30.9 mg/day (95% CI: 18.0 to 43.7). Our meta-analysis revealed a mortality rate of 29.0% (95% CI: 15.0% to 48.6%). Clinicians should maintain a high index of suspicion for cryptococcal and tuberculosis (TB) meningitis in patients with SLE with suspected CNS infection, particularly in those with higher SLEDAI and on higher doses of systemic corticosteroids. In conclusion, initiation of empiric antituberculous treatment for patients with SLE who are highly suspected to have CNS TB is warranted while awaiting the results of diagnostic tests. Antifungals might also be potentially useful empirically in patients with SLE who are suspected to have fungal CNS infections. However, with respect to side effects such as toxicity and high cost of antifungals, decision regarding early antifungal therapy should be guided by early and less time-consuming fungal diagnostic tests.

Anticoagulant Treatment for Pediatric Infection-Related Cerebral Venous Thrombosis.

BACKGROUND: We aimed to describe the clinical presentation, risk of bleeding and recurrent thrombosis, and perioperative anticoagulant management of children with cerebral venous thrombosis (CVT) and an associated head or neck infection. METHODS: In this subgroup analysis of the EINSTEIN-Jr study, we included children with CVT and an associated head or neck infection who received therapeutic anticoagulants with either low-molecular-weight heparin (with or without subsequent vitamin K antagonists) or rivaroxaban for a period of 3 months. Analyses are descriptive. RESULTS: Of 74 included children, 59 (80%) had otomastoiditis, 21 (28%) a central nervous system infection, 18 (24%) sinusitis, and 9 (12%) another upper respiratory tract infection; 29 (39%) had infection of multiple regions of the head or neck. All 74 children received antibiotics and therapeutic anticoagulants; 41 (55%) underwent surgery, of whom 34 were diagnosed with CVT preoperatively. Anticoagulation was started before surgery in 12 children and interrupted 0-1 days prior to surgery. Anticoagulation was (re)started in all 34 children at a median of 1 day (interquartile range: 0-1) postoperatively, in therapeutic doses in 94%. Overall, one child (1%, 95% confidence interval: 0-7) had recurrent thrombosis, and one (1%, 95% confidence interval: 0-7) had major bleeding; neither was associated with surgery. At 3 months, no children had died, 3 (4%) had persistent focal neurologic deficits, and 2 (3%) had impaired vision. CONCLUSIONS: Children with CVT and an associated head or neck infection administered therapeutic anticoagulants generally had low risks of bleeding and thrombotic complications, including those who had surgical interventions with delay or interruption of anticoagulation.

Central Nervous System Infections Due to Streptococcus anginosus Group: A Single-Center Case Series.

BACKGROUND: The Streptococcus anginosus group is known for its pathogenicity and tendency for abscess formation. The S anginosus group also causes brain abscesses, yet few studies describe this presentation in the pediatric neurology literature. We describe 5 patients with central nervous system infection due to S anginosus group evaluated by child neurologists at the University of Iowa from 2014 to 2020. METHODS: We performed a retrospective case series review of electronic medical records detailing the clinical presentation and course of pediatric patients with S anginosus group-associated central nervous system infection. RESULTS: We identified 4 males and 1 female (8, 11, 14, 16, and 21 years). Brain imaging showed abscesses in 4 cases and empyema in 1. All underwent neurosurgical intervention and antibiotic treatment. Cultures obtained during the neurosurgical procedure grew S anginosus group (4 cases with Streptococcus intermedius and 1 with Streptococcus constellatus). An 8-year-old boy with a delayed diagnosis died from brain herniation. CONCLUSIONS: Central nervous system infections due to the S anginosus group can be life-threatening. Neuroimaging plays a key role in the early identification of abscesses. Prompt surgical intervention and timely initiation of antibiotics are critical for optimal outcomes.

Cellular and Molecular Effects of SARS-CoV-2 Linking Lung Infection to the Brain.

In December 2019, a new viral disease emerged and quickly spread all around the world. In March 2020, the COVID-19 outbreak was classified as a global pandemic and by June 2021, the number of infected people grew to over 170 million. Along with the patients' mild-to-severe respiratory symptoms, reports on probable central nervous system (CNS) effects appeared shortly, raising concerns about the possible long-term detrimental effects on human cognition. It remains unresolved whether the neurological symptoms are caused directly by the SARS-CoV-2 infiltration in the brain, indirectly by secondary immune effects of a cytokine storm and antibody overproduction, or as a consequence of systemic hypoxia-mediated microglia activation. In severe COVID-19 cases with impaired lung capacity, hypoxia is an anticipated subsidiary event that can cause progressive and irreversible damage to neurons. To resolve this problem, intensive research is currently ongoing, which seeks to evaluate the SARS-CoV-2 virus' neuroinvasive potential and the examination of the antibody and autoantibody generation upon infection, as well as the effects of prolonged systemic hypoxia on the CNS. In this review, we summarize the current research on the possible interplay of the SARS-CoV-2 effects on the lung, especially on alveolar macrophages and direct and indirect effects on the brain, with special emphasis on microglia, as a possible culprit of neurological manifestation during COVID-19.

Risk factors for neurological complications in children with Flavivirus infection.

This study aims to characterize the acute neurological manifestations caused by DENV, ZIKV, and YFV during hospitalization; identify the risk factors associated with persistent neurological complications after discharge; and evaluate the time to resolution during clinical follow-up. A prospective study evaluated 505 children, between March 2014 and July 2019, hospitalized with neurological manifestations and that doctors suspected infection of the central nervous system (CNS). Viral infection of collected cerebrospinal fluid (CSF) was confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR). Patients were clinically followed up after hospital discharge. Analysis of predictive factors and survival curves was performed. This study identified clinical symptoms and changes in the CSF laboratory, electroencephalogram (EEG), and CNS image as predictors of complications in children with confirmed infection in the CNS by DENV, ZIKV, or YFV. No statistical difference was found (p value 0.574) in the time to the resolution of complications in children after hospital discharge between the three types of flaviviruses. Children with YFV, detected in CSF samples, had a 53% higher risk of developing neurological complications. Performing etiological diagnosis by RT-PCR of CSF samples of children with neurological manifestations, especially during Flavivirus outbreaks, is an essential tool for improving the prognosis and clinical follow-up of these patients.