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The American Journal of Emergency... Jun 2024We present a three patient case series of infants who presented to the pediatric emergency department with fever, bulging anterior fontanelle (BAF), and an omicron...
We present a three patient case series of infants who presented to the pediatric emergency department with fever, bulging anterior fontanelle (BAF), and an omicron variant COVID-19 infection. All patients had a benign course, none developed meningitis, and all had symptom resolution after two days. Considerations for neuroimaging and lumbar puncture are discussed. This case series adds to the previously published case reports of infants with COVID-19, fever and BAF and further describes a variant in the presenting symptomology of COVID-19 infection in infants under 12 months. Acute and primary care providers who treat infants should consider COVID-19 testing in patients who are well appearing, with fever and BAF.
PubMed: 38866626
DOI: 10.1016/j.ajem.2024.06.003 -
Cell Reports. Medicine Jun 2024Leptomeningeal disease (LMD) remains a rapidly lethal complication for late-stage melanoma patients. Here, we characterize the tumor microenvironment of LMD and...
Leptomeningeal disease (LMD) remains a rapidly lethal complication for late-stage melanoma patients. Here, we characterize the tumor microenvironment of LMD and patient-matched extra-cranial metastases using spatial transcriptomics in a small number of clinical specimens (nine tissues from two patients) with extensive in vitro and in vivo validation. The spatial landscape of melanoma LMD is characterized by a lack of immune infiltration and instead exhibits a higher level of stromal involvement. The tumor-stroma interactions at the leptomeninges activate tumor-promoting signaling, mediated through upregulation of SERPINA3. The meningeal stroma is required for melanoma cells to survive in the cerebrospinal fluid (CSF) and promotes MAPK inhibitor resistance. Knocking down SERPINA3 or inhibiting the downstream IGR1R/PI3K/AKT axis results in tumor cell death and re-sensitization to MAPK-targeting therapy. Our data provide a spatial atlas of melanoma LMD, identify the tumor-promoting role of meningeal stroma, and demonstrate a mechanism for overcoming microenvironment-mediated drug resistance in LMD.
Topics: Melanoma; Humans; Tumor Microenvironment; Meningeal Neoplasms; Stromal Cells; Animals; Cell Line, Tumor; Mice; Gene Expression Regulation, Neoplastic; Transcriptome; Gene Expression Profiling; Meninges; Drug Resistance, Neoplasm; Signal Transduction; Female
PubMed: 38866016
DOI: 10.1016/j.xcrm.2024.101606 -
Frontiers in Immunology 2024Historically, the central nervous system (CNS) was regarded as 'immune-privileged', possessing its own distinct immune cell population. This immune privilege was thought... (Review)
Review
Historically, the central nervous system (CNS) was regarded as 'immune-privileged', possessing its own distinct immune cell population. This immune privilege was thought to be established by a tight blood-brain barrier (BBB) and blood-cerebrospinal-fluid barrier (BCSFB), which prevented the crossing of peripheral immune cells and their secreted factors into the CNS parenchyma. However, recent studies have revealed the presence of peripheral immune cells in proximity to various brain-border niches such as the choroid plexus, cranial bone marrow (CBM), meninges, and perivascular spaces. Furthermore, emerging evidence suggests that peripheral immune cells may be able to infiltrate the brain through these sites and play significant roles in driving neuronal cell death and pathology progression in neurodegenerative disease. Thus, in this review, we explore how the brain-border immune niches may contribute to the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). We then discuss several emerging options for harnessing the neuroimmune potential of these niches to improve the prognosis and treatment of these debilitative disorders using novel insights from recent studies.
Topics: Humans; Neurodegenerative Diseases; Animals; Blood-Brain Barrier; Brain; Immune Privilege
PubMed: 38863704
DOI: 10.3389/fimmu.2024.1380063 -
Pediatric Rheumatology Online Journal Jun 2024To characterize the clinical features and to identify the predictors of recurrence of histiocytic necrotizing lymphadenitis (HNL) in Chinese children.
OBJECTIVES
To characterize the clinical features and to identify the predictors of recurrence of histiocytic necrotizing lymphadenitis (HNL) in Chinese children.
STUDY DESIGN
This study retrospectively analyzed the clinical characteristics, laboratory and pathological findings, and recurrence status of children diagnosed with HNL at a single center in China from January 2018 to May 2023. Logistic regression analysis was employed to identify predictors of HNL recurrence.
RESULTS
181 Chinese children with histopathologically confirmed HNL were enrolled (121 males and 60 females). The mean age was 9.3 ± 2.9 years. The most prominent clinical features were fever (98.9%) and cervical lymphadenopathy (98.3%). Aseptic meningitis was the most frequent complication (38.5%), while hemophagocytic lymphohistiocytosis and autoimmune disease were rare (1.7% and 1.2%, respectively). Recurrence occurred in 12.7% of patients. Erythrocyte sedimentation rate (> 30 mm/h) was the significant predictors of HNL recurrence, with odds ratios of 6.107, respectively.
CONCLUSION
Our study demonstrates that fever and cervical lymphadenopathy are the most frequent clinical manifestations of HNL in Chinese children, which often coexist with aseptic meningitis. HNL patients with risk factors require follow-up for recurrence.
Topics: Humans; Histiocytic Necrotizing Lymphadenitis; Male; Female; Child; Retrospective Studies; Recurrence; China; Lymphadenopathy; Fever; Risk Factors; Child, Preschool; Adolescent; Meningitis, Aseptic; East Asian People
PubMed: 38862943
DOI: 10.1186/s12969-024-00996-y -
BMJ Open Jun 2024This study aimed to evaluate the efficiency of nanopore sequencing for the early diagnosis of tuberculous meningitis (TBM) using cerebrospinal fluid and compared it with...
OBJECTIVE
This study aimed to evaluate the efficiency of nanopore sequencing for the early diagnosis of tuberculous meningitis (TBM) using cerebrospinal fluid and compared it with acid-fast bacilli (AFB) smear, mycobacterial growth indicator tube culture and Xpert (MTB)/rifampicin (RIF).
DESIGN
Single-centre retrospective study.
SETTING
The Tuberculosis Diagnosis and Treatment Center of Zhejiang Chinese and Western Medicine Integrated Hospital.
PARTICIPANTS
We enrolled 64 adult patients with presumptive TBM admitted to our hospital from August 2021 to August 2023.
METHODS
We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of AFB smear, culture, Xpert MTB/RIF and nanopore sequencing to evaluate their diagnostic efficacy compared with a composite reference standard for TBM.
RESULTS
Among these 64 patients, all tested negative for TBM by AFB smear. The sensitivity, specificity, PPV and NPV were 11.11%, 100%, 100% and 32.2% for culture, 13.33%, 100%, 100% and 2.76% for Xpert MTB/RIF, and 77.78%, 100%, 100% and 65.52% for nanopore sequencing, respectively.
CONCLUSION
The diagnostic accuracy of the nanopore sequencing test was significantly higher than that of conventional testing methods used to detect TBM.
Topics: Humans; Tuberculosis, Meningeal; Retrospective Studies; Male; Female; Adult; China; Middle Aged; Nanopore Sequencing; Mycobacterium tuberculosis; Sensitivity and Specificity; Predictive Value of Tests; Aged; Young Adult; Cerebrospinal Fluid
PubMed: 38862231
DOI: 10.1136/bmjopen-2023-080904 -
Cureus May 2024Meningeal solitary fibrous tumors (SFTs) are a rare central nervous system neoplastic process, resulting in frequent misdiagnosis as meningioma prior to pathologic...
Meningeal solitary fibrous tumors (SFTs) are a rare central nervous system neoplastic process, resulting in frequent misdiagnosis as meningioma prior to pathologic analysis. Appropriate diagnosis is essential to lowering morbidity and mortality, as Grade II or III SFTs are aggressive neoplasms that possess metastatic potential. The existing data may suggest that intracranial SFTs primarily afflict those in their fourth through sixth decades of life. However, we present the case of a patient outside this demographic presenting with symptoms that we were unable to identify in any prior reports. A 21-year-old male in the United States Navy presented to the emergency department (ED) with a two-month history of progressive headaches, leading to nausea and emesis. The patient also endorsed a daily incidence of the same olfactory hallucination followed by several minutes of palpitations, flushing, and dizziness. His neurologic exam was unremarkable, but imaging in the ED revealed a large mass abutting the right medial sphenoid wing. The radiographic appearance of the mass with a dural tail led to a preoperative diagnosis of meningioma. However, pathologic analysis following gross total resection identified the mass as an SFT. A brief literature review complementary to this case underscored the high variability of intracranial SFT case presentations with a relative scarcity of epidemiologic data due to rarity. This review identified that it was common to initially diagnose SFTs as meningioma, similar to this particular case. This emphasizes the importance of an appropriate pathologic diagnosis. This case adds to the existing literature as anecdotal evidence of SFT occurring in a young patient and a unique symptom profile most notable for olfactory hallucination and dysautonomia as features of focal seizure.
PubMed: 38860106
DOI: 10.7759/cureus.60104 -
International Medical Case Reports... 2024[This corrects the article DOI: 10.2147/IMCRJ.S438457.].
[This corrects the article DOI: 10.2147/IMCRJ.S438457.].
PubMed: 38859943
DOI: 10.2147/IMCRJ.S481496 -
BMC Neurology Jun 2024The treatment regimen for tuberculous meningitis (TBM) remains unclear and requires optimization. There are some reports on successful adjunct intrathecal dexamethasone... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The treatment regimen for tuberculous meningitis (TBM) remains unclear and requires optimization. There are some reports on successful adjunct intrathecal dexamethasone and isoniazid (IDI) treatment strategies for TBM, however, there is equivocal evidence on their efficacy and safety.
METHODS
A comprehensive search of English and Chinese databases was conducted from inception to February 2024. A meta-analysis was performed on randomized controlled trials (RCTs) estimating the effects of adjunct IDI on conventional anti-TB (C anti-TB) treatments or C anti-TB alone. Efficacy, adverse reaction rate, cerebrospinal fluid (CSF) leukocytes, and CSF protein were used as primary outcome indicators. CSF glucose, CSF chlorides, CSF pressure, recovery time for laboratory indicators and recovery time for clinical symptoms were used as secondary outcome indicators.
RESULTS
A total of 17 studies involving 1360 (IDI group vs. C anti-TB group: 392 vs. 372; higher-dose IDI group vs. lower-dose IDI group: 319 vs. 277) patients were included in our analysis. Efficacy was significantly higher (RR 1.3, 95% CI 1.2-1.4, P < 0.001) and adverse reaction rate was significantly lower in the IDI groups (RR 0.59, 95% CI 0.37-0.92, P = 0.021). Furthermore, CSF leukocytes (WMD - 29.33, 95% CI [- 40.64 to-18.02], P < 0.001) and CSF protein (WMD - 0.79, 95%CI [-0.96 to-0.61], P < 0.001) were significantly lower in the IDI groups. Recovery time indicators were all shorter in the IDI groups, fever (SMD - 2.45, 95% CI [-3.55 to-1.35], P < 0.001), coma (SMD-3.75, 95% CI [-4.33 to-3.17], P < 0.001), and headache (SMD - 3.06, 95% CI [- 4.05 to-2.07], P < 0.001), respectively. Higher-dose IDI was more effective than lower-dose IDI (RR 1.23, 95% CI 1.14-1.33, P < 0.001), with no significant difference in adverse reaction rate between the two (RR 0.82, 95%CI 0.43-1.56, P = 0.544).
CONCLUSION
Adjunct IDI with C anti-TB can enhance therapeutic outcomes and reduce adverse reaction rate in adult TBM patients, with higher-dose IDI showing superior efficacy. These findings highlight the potential of IDI as an adjunctive therapy in TBM management. However, more high-quality RCTs from more regions should be conducted to support our results.
TRIAL REGISTRATION
Retrospectively registered in PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023388860 .
Topics: Humans; Tuberculosis, Meningeal; Dexamethasone; Isoniazid; Antitubercular Agents; Drug Therapy, Combination; Injections, Spinal; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 38858618
DOI: 10.1186/s12883-024-03701-4 -
Spinal Cord Series and Cases Jun 2024Syringomyelia, or the formation of fluid-filled cysts within the spinal cord, associated with delayed spinal arachnoiditis is an uncommon complication of aneurysmal...
BACKGROUND AND IMPORTANCE
Syringomyelia, or the formation of fluid-filled cysts within the spinal cord, associated with delayed spinal arachnoiditis is an uncommon complication of aneurysmal subarachnoid haemorrhage. To date, about 18 cases have been reported in medical literature, with just two reported in patients under the age of 35 years.
CLINICAL PRESENTATION
A 27-year-old female patient complained of sudden, severe headaches in the occipital region, nuchal rigidity, and drowsiness when she presented at our institution. A head computed tomography scan revealed intraventricular bleeding in the lateral and fourth ventricles with more extensive haemorrhaging in the frontal horns. A left posterior inferior cerebellar artery (PICA) aneurysm was confirmed via digital subtraction angiogram, and endovascular embolization was done. Two years later, the patient reported intense pain in the lower back along with symptoms suggestive of spinal cord compression. Spinal magnetic resonance imaging (MRI) showed spinal adhesions from C1 to L4, syringomyelia with some vasogenic oedema extending from T3 to T9 level, and a cyst in the lumbar region. Consequently, a right hemilaminectomy was performed along with microsurgical release of arachnoid adhesions and placement of a subdural drain. Radiological and symptomatic improvements were observed. Since then, the patient's clinical condition has remained stable during the past three years of follow-up visits.
CONCLUSIONS
Literature on optimal treatment modalities and patient prognosis is scarce and debated. The time for symptom improvement depends on the level and extent of spinal cord involvement. Rehabilitation may be required for most patients, as complete symptomatic recovery may not be attainable.
Topics: Humans; Female; Arachnoiditis; Adult; Syringomyelia; Subarachnoid Hemorrhage
PubMed: 38858362
DOI: 10.1038/s41394-024-00654-1 -
JAMA Network Open Jun 2024Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18...
IMPORTANCE
Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity.
OBJECTIVE
To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge.
DESIGN, SETTING, AND PARTICIPANTS
This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021.
EXPOSURE
Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke.
MAIN OUTCOMES AND MEASURES
The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2-related condition.
RESULTS
Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P < .001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations (P = .002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P = .001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P = .009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge.
CONCLUSIONS AND RELEVANCE
The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.
Topics: Humans; COVID-19; Child; Female; Male; Child, Preschool; Hospitalization; Adolescent; Prospective Studies; SARS-CoV-2; Systemic Inflammatory Response Syndrome; Nervous System Diseases; Infant; Severity of Illness Index
PubMed: 38857050
DOI: 10.1001/jamanetworkopen.2024.14122