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Parasites & Vectors Apr 2024Infection with Angiostrongylus cantonensis (AC) in humans or mice can lead to severe eosinophilic meningitis or encephalitis, resulting in various neurological...
BACKGROUND
Infection with Angiostrongylus cantonensis (AC) in humans or mice can lead to severe eosinophilic meningitis or encephalitis, resulting in various neurological impairments. Developing effective neuroprotective drugs to improve the quality of life in affected individuals is critical.
METHODS
We conducted a Gene Ontology enrichment analysis on microarray gene expression (GSE159486) in the brains of AC-infected mice. The expression levels of melanin-concentrating hormone (MCH) were confirmed through real-time quantitative PCR (RT-qPCR) and immunofluorescence. Metabolic parameters were assessed using indirect calorimetry, and mice's energy metabolism was evaluated via pathological hematoxylin and eosin (H&E) staining, serum biochemical assays, and immunohistochemistry. Behavioral tests assessed cognitive and motor functions. Western blotting was used to measure the expression of synapse-related proteins. Mice were supplemented with MCH via nasal administration.
RESULTS
Postinfection, a marked decrease in Pmch expression and the encoded MCH was observed. Infected mice exhibited significant weight loss, extensive consumption of sugar and white fat tissue, reduced movement distance, and decreased speed, compared with the control group. Notably, nasal administration of MCH countered the energy imbalance and dyskinesia caused by AC infection, enhancing survival rates. MCH treatment also increased the expression level of postsynaptic density protein 95 (PSD95) and microtubule-associated protein-2 (MAP2), as well as upregulated transcription level of B cell leukemia/lymphoma 2 (Bcl2) in the cortex.
CONCLUSIONS
Our findings suggest that MCH improves dyskinesia by reducing loss of synaptic proteins, indicating its potential as a therapeutic agent for AC infection.
Topics: Animals; Female; Male; Mice; Angiostrongylus cantonensis; Brain; Energy Metabolism; Hypothalamic Hormones; Melanins; Pituitary Hormones; Strongylida Infections
PubMed: 38654385
DOI: 10.1186/s13071-024-06267-9 -
Experimental Cell Research Apr 2024A major obstacle in improving survival in pediatric T-cell acute lymphoblastic leukemia is understanding how to predict and treat leukemia relapse in the CNS. Leukemia...
A major obstacle in improving survival in pediatric T-cell acute lymphoblastic leukemia is understanding how to predict and treat leukemia relapse in the CNS. Leukemia cells are capable of infiltrating and residing within the CNS, primarily the leptomeninges, where they interact with the microenvironment and remain sheltered from systemic treatment. These cells can survive in the CNS, by hijacking the microenvironment and disrupting normal functions, thus promoting malignant transformation. While the protective effects of the bone marrow niche have been widely studied, the mechanisms behind leukemia infiltration into the CNS and the role of the CNS niche in leukemia cell survival remain unknown. We identified a dysregulated gene expression profile in CNS infiltrated T-ALL and CNS relapse, promoting cell survival, chemoresistance, and disease progression. Furthermore, we discovered that interactions between leukemia cells and human meningeal cells induced epigenetic alterations, such as changes in histone modifications, including H3K36me3 levels. These findings are a step towards understanding the molecular mechanisms promoting leukemia cell survival in the CNS microenvironment. Our results highlight genetic and epigenetic alterations induced by interactions between leukemia cells and the CNS niche, which could potentially be utilized as biomarkers to predict CNS infiltration and CNS relapse.
Topics: Child; Humans; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Cell Survival; Precursor Cell Lymphoblastic Leukemia-Lymphoma; T-Lymphocytes; Recurrence; Cell Cycle; Tumor Microenvironment
PubMed: 38561062
DOI: 10.1016/j.yexcr.2024.114015 -
Cureus Mar 2024Carcinomatous meningitis (CM) is characterized by the multifocal dissemination of malignant cells into the cerebrospinal fluid (CSF), pia mater, and subarachnoid space....
Carcinomatous meningitis (CM) is characterized by the multifocal dissemination of malignant cells into the cerebrospinal fluid (CSF), pia mater, and subarachnoid space. Involvement can occur in the advanced stage of malignancy, causing multifocal involvement and a wide array of symptoms. Diagnosis requires suspicions and a multimodal approach that includes imaging, lumbar puncture, and diagnostic laboratory evaluation. This case represents a female with a history of non-Hodgkin's lymphoma (NHL) and venous thromboembolism on chronic anticoagulation who presented due to acute encephalopathy, hallucinations, and right cranial nerve III palsy for 10 days before arrival. Computed tomography (CT) and angiography of the brain did not show any intracranial abnormalities. Subsequent magnetic resonance imaging (MRI) was without signs of infarction, hemorrhage, or abnormal enhancement, with the MRI of the orbits showing asymmetric linear enhancement anterior to the superior pons and midbrain on the right. Initial differential included a paraneoplastic syndrome, but there was no obvious evidence of pathological enhancement on MRI. Due to progressive bulbar symptoms, a lumbar puncture was performed with cerebrospinal fluid diagnostic workup with cytology showing monoclonal B-cell proliferation consistent with lymphoma. This case illustrates a rare but specific finding of CM as cranial nerve III palsy symptoms in this patient who did not have imaging findings that would reflect her symptoms on the initial MRI of the brain. Furthermore, diagnosing CM is complex and involves a combination of multiple diagnostic and treatment modalities. It is important to recognize the condition early to improve the patient's quality of life, prolong survival, and stabilize neurological deterioration.
PubMed: 38623120
DOI: 10.7759/cureus.56277 -
Cancer Reports (Hoboken, N.J.) Jan 2024Lifestyle is associated with meningioma risk in the general population.
BACKGROUND
Lifestyle is associated with meningioma risk in the general population.
AIMS
We assessed longitudinal associations between lifestyle-associated factors and subsequent meningiomas in childhood cancer survivors.
METHODS AND RESULTS
Childhood cancer survivors age ≥18 years in the St. Jude Lifetime Cohort Study were evaluated for body composition, self-reported physical activity, cardiopulmonary fitness, muscle strength, smoking, and alcohol consumption at baseline. Time to first meningioma analyses were performed, adjusted for sex, age at diagnosis and baseline assessment, treatment decade, and childhood cancer treatment exposures. The study included 4,072 survivors (47% female; [mean (SD)] 9 (6) years at diagnosis; 30 (8.5) years at the start of follow-up, with 7.0 (3.3) years of follow-up). 30% of the participants were survivors of acute lymphoblastic leukemia and 29% of the participants had received cranial radiation. During follow-up, 90 participants developed ≥1 meningioma, of whom 73% were survivors of acute lymphoblastic leukemia, with cranial radiation being the strongest risk factor (relative risk [RR] 29.7, 95% confidence interval [CI] 10.6-83.2). Muscle strength assessed by knee extension was associated with a lower risk of developing a meningioma in the adjusted analyses (RR 0.5, 95% CI 0.2-1.0, p = 0.04 for quartiles 3-4 vs. 1). No other lifestyle-associated variable was associated with subsequent meningioma.
CONCLUSION
Independent of cranial radiation, muscle strength was associated with a lower risk of developing a subsequent meningioma in childhood cancer survivors.
Topics: Humans; Child; Female; Adolescent; Male; Meningioma; Cohort Studies; Cancer Survivors; Life Style; Meningeal Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 38009808
DOI: 10.1002/cnr2.1944 -
IDCases 2023Invasive listeriosis most often presents as bacteremia or neurolisteriosis. Cerebral infection mostly manifests as meningitis or meningoencephalitis, but cerebral...
INTRODUCTION
Invasive listeriosis most often presents as bacteremia or neurolisteriosis. Cerebral infection mostly manifests as meningitis or meningoencephalitis, but cerebral abscesses are a rare manifestation.
CASE PRESENTATION
We present the rare case of a 51-year old patient with progressive right sided hemiparesis caused by a cerebral abscess due to infection. The initially suspected cerebral ischemia or bleeding was ruled out. Magnetic resonance imaging led to the suspected diagnosis of an angiocentric lymphoma. An open cerebral biopsy revealed an intracranial abscess formation. After abscess evacuation and identification of anti-infective treatment with ampicillin and gentamicin was started. After repeated cerebral imaging with signs of ongoing tissue inflammation after 6 weeks we chose to prolong the therapy with oral amoxicillin until resolution of signs of intracerebral inflammation after 12 weeks, documented by repeated cerebral magnetic resonance imaging. During hospitalization, the patient was diagnosed with diabetes mellitus type II and treatment was initiated. The patient was discharged without any persistent neurologic deficits.
DISCUSSION
For the treatment of bacterial brain abscesses, 4-6 weeks of intravenous antimicrobial treatment after surgical drainage are recommended. However, first line therapy of invasive cerebral listeriosis is not well established. We decided to use a combined treatment using ampicillin and gentamicin, followed by prolonged oral treatment due to ongoing tissue inflammation.
CONCLUSION
No evidence-based treatment recommendations are available for brain abscess caused by . We report a case with favorable outcome after anti-infective ampicillin- and gentamicin-based therapy. Systematic assessment of treatment would be desirable.
PubMed: 37577046
DOI: 10.1016/j.idcr.2023.e01864 -
Cureus May 2024Immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-known side effect of chimeric antigen receptor (CAR) T-cell therapy but has occasionally been...
Glofitamab-Associated Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Presenting as Serial Seizures and Responding Positively to Antiseizure Drugs and Anakinra: A Case Report.
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-known side effect of chimeric antigen receptor (CAR) T-cell therapy but has occasionally been described with immune checkpoint inhibitors as well. Glofitamab-associated ICANS with a bispecific monoclonal antibody has rarely been reported. The patient is a 63-year-old male with a history of mantle cell lymphoma, diagnosed at age 37, and aggressive large-cell B-cell lymphoma, diagnosed at age 50. Despite adequate chemotherapy, immunotherapy, autologous stem cell transplantation, and CAR T-cell therapy, there were several relapses, including meningeal carcinomatosis at age 61 and intracerebral lymphoma at age 62. For this reason, glofitamab was started. One week after the ninth cycle, the patient developed drowsiness, behavioral changes, word-finding difficulties, aphasia, focal to bilateral tonic-clonic seizures, and focal onset seizures, which resolved after 16 days with levetiracetam, valproic acid, lorazepam, and midazolam. Since there was no infectious disease, electrolyte disturbance, metabolic disorder, cardiovascular disease, or relapse of lymphoma, glofitamab-associated ICANS was suspected, and anakinra was administered. The case shows that ICANS with drowsiness, behavioral changes, aphasia, and seizures can develop with glofitamab and that patients with structural brain abnormalities may be prone to this.
PubMed: 38910651
DOI: 10.7759/cureus.60833 -
Journal of Clinical Medicine Research Apr 2024A 67-year-old woman was admitted to the Hematology Department in 2014 with complaints of weakness and a low-grade fever. After conducting various tests, it was confirmed...
A 67-year-old woman was admitted to the Hematology Department in 2014 with complaints of weakness and a low-grade fever. After conducting various tests, it was confirmed that she had Waldenstrom macroglobulinemia. She underwent several rounds of chemotherapy and maintenance therapy with rituximab, which resulted in a good clinical response. However, in 2019, an abnormal growth in the soft tissues of patient's frontal region was discovered, which was diagnosed as lymphoplasmacytic lymphoma. This later progressed to an intracranial lesion. The patient underwent radiation therapy for both the extramedullary and intracranial growths, which had a positive effect. A year later, she developed a lesion in her lymph nodes and soft tissues of her right leg, which was confirmed to be a recurrence of Waldenstrom disease. She underwent further treatment and is currently in complete remission. This case highlights the rare occurrence of relapse in Waldenstrom disease and the challenges in diagnosing extramedullary lesions. It also demonstrates the success of modern treatment approaches using a combination of therapies.
PubMed: 38715560
DOI: 10.14740/jocmr5115 -
Cureus May 2024Meningitis, an infection of the meninges of the central nervous system (CNS), can advance quickly and carries a mortality rate reaching 30% among affected patients. It...
Meningitis, an infection of the meninges of the central nervous system (CNS), can advance quickly and carries a mortality rate reaching 30% among affected patients. It may become complicated by conditions such as hydrocephalus, ventriculitis, and cerebral abscess. Here, we describe a case of meningitis that was complicated by pyogenic ventriculitis and hydrocephalus in a patient with diffuse large B-cell lymphoma (DLBCL) who underwent chemotherapy and radiotherapy. The patient presented with acute change in mental status and high-grade fever, with few episodes of non-bloody vomiting. Blood culture and cerebrospinal fluid (CSF) culture grew which was sensitive to ceftriaxone. CT scan of the head showed ventriculomegaly, pansinusitis, and a large left mastoid effusion. MRI of the brain showed layering in ventricles, hydrocephalus, and dural enhancement consistent with pachymeningitis. She was treated with ceftriaxone for 21 days with a meaningful outcome. She was discharged home with near-baseline mental capacity for further physical therapy.
PubMed: 38903366
DOI: 10.7759/cureus.60800 -
Acta Neurologica Belgica Oct 2023
Topics: Humans; Hodgkin Disease; Tuberculosis, Meningeal; Syndrome; Limbic Encephalitis; Magnetic Resonance Imaging
PubMed: 35831778
DOI: 10.1007/s13760-022-02019-7