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Intractable & Rare Diseases Research May 2024The Japanese Research Group for Neuro-infectious Diseases was founded in August 1996, and by 2004 it had evolved into the Japanese Society for Neuro-infectious Diseases....
The Japanese Research Group for Neuro-infectious Diseases was founded in August 1996, and by 2004 it had evolved into the Japanese Society for Neuro-infectious Diseases. The Society focuses on neuroinfectious conditions (., encephalitis/encephalopathy, myelitis, and meningitis), providing a venue for academic presentations and exchanges. Clinical guidelines for major neurological infectious diseases are also published by the Society, in order to meet the social demands of each era. Although the threat of herpes simplex encephalitis has declined due to acyclovir's introduction, the frequency of encephalitis or peripheral neuropathy caused by varicella-zoster virus is increasing. In Japan, prion disease, human T-cell leukemia virus-1 (HTLV-1)-associated myelopathy (HAM), subacute sclerosing panencephalitis (SSPE), and progressive multifocal leukoencephalopathy (PML) are designated as intractable diseases. The incidence of prion disease is 1.8/1,000,000 individuals, with the sporadic type accounting for 80%. Prion disease is fatal, and effective medications are awaited. HAM's prevalence is ~3/100,000 individuals, with a male-to-female ratio of 1:2-3. HAM is common in western Japan, including Kyushu and Okinawa. The prevalence of PML is rising with the spread of both immunosuppressive therapy for transplantation and treatment for multiple sclerosis. From late 2019 through 2020, the world faced a global outbreak of coronavirus disease 2019 (COVID-19) due to virus mutations, and the threat of new mutations persists. Close attention should be paid to the emergence of new neurological infections that could arise from abnormal weather patterns and/or a decline in immune function due to aging.
PubMed: 38836177
DOI: 10.5582/irdr.2024.01008 -
Antibiotics (Basel, Switzerland) May 2024Ventriculitis and nosocomial meningitis caused by carbapenem-resistant Gram-negative and vancomycin-resistant Gram-positive bacteria represent a growing treatment...
Ventriculitis and nosocomial meningitis caused by carbapenem-resistant Gram-negative and vancomycin-resistant Gram-positive bacteria represent a growing treatment challenge. A case of ventriculitis and bacteremia caused by carbapenem-resistant, KPC-producing and vancomycin-resistant in a young woman with acute leukemia who was successfully treated with meropenem/vaborbactam (MVB), rifampicin, and linezolid is described in this paper. This case report emphasizes the importance of a multidisciplinary strategy, including infectious focus control, for the treatment of device-associated central nervous system (CNS) infections from multidrug-resistant bacteria. Considering the novel resistance patterns, more research on drug penetration into the central nervous system, as well as on the necessity of association therapies, is needed.
PubMed: 38786160
DOI: 10.3390/antibiotics13050432 -
Antibiotics (Basel, Switzerland) Apr 2024Central nervous system (CNS) lesions, especially invasive fungal diseases (IFDs), in immunocompromised patients pose a great challenge in diagnosis and treatment. We...
Central nervous system (CNS) lesions, especially invasive fungal diseases (IFDs), in immunocompromised patients pose a great challenge in diagnosis and treatment. We report the case of a 48-year-old man with acute myeloid leukaemia and probable pulmonary aspergillosis, who developed hyposthenia of the left upper limb, after achieving leukaemia remission and while on voriconazole. Magnetic resonance imaging (MRI) showed oedematous CNS lesions with a haemorrhagic component in the right hemisphere with lepto-meningitis. After 2 weeks of antibiotics and amphotericin-B, brain biopsy revealed chronic inflammation with abscess and necrosis, while cultures were negative. Clinical recovery was attained, he was discharged on isavuconazole and allogeneic transplant was postponed, introducing azacitidine as a maintenance therapy. After initial improvement, MRI worsened; brain biopsy was repeated, showing similar histology; and 16S metagenomics sequencing analysis was positive (, ). Despite 1 month of meropenem, MRI did not improve. The computer tomography and PET scan excluded extra-cranial infectious-inflammatory sites, and auto-immune genesis (sarcoidosis, histiocytosis, CNS vasculitis) was deemed unlikely due to the histological findings and unilateral lesions. We hypothesised possible IFD with peri-lesion inflammation and methyl-prednisolone was successfully introduced. Steroid tapering is ongoing and isavuconazole discontinuation is planned with close follow-up. In conclusion, the management of CNS complications in immunocompromised patients needs an interdisciplinary approach.
PubMed: 38786116
DOI: 10.3390/antibiotics13050387 -
Cureus Mar 2024Posterior reversible encephalopathy syndrome (PRES) is an uncommon yet severe neurological disorder characterized by a combination of clinical and radiological features....
Posterior reversible encephalopathy syndrome (PRES) is an uncommon yet severe neurological disorder characterized by a combination of clinical and radiological features. Common clinical presentations of PRES include headaches, seizures, altered mental status ranging from lethargy to coma, visual disturbances, and behavior changes. This case report outlines the occurrence of hemorrhagic PRES in an 11-year-old girl with B-cell acute lymphoblastic leukemia (ALL) relapse. Hospitalized for ALL relapse, the patient underwent reinduction chemotherapy. On the ninth day of admission, she had a generalized tonic-clonic seizure with a blood pressure peak of 170/120 mmHg. Magnetic resonance imaging (MRI) and a seizure episode suggested PRES. Initially, after the first tonic-clonic seizure, the neurological examination was normal, but after the second seizure, the meningeal symptoms were negative, and gaze palsy and right-sided homonymous hemianopsia were observed; muscle strength was symmetrically reduced in the upper and lower extremities and reflexes were symmetrical and diminished. A bilateral Babinski reflex was observed at the time of examination; the patient had mild motor aphasia, and she opened her eyes only in response to tactile stimulation. A follow-up MRI four days after the second seizure episode showed extensive PRES damage with hemorrhagic changes. Over two weeks, the patient's neurological status and blood pressure gradually improved, with persistent changes in the visual field. Subsequent MRI revealed a significant reduction in PRES lesions, but residual hemorrhage measuring 6x4 cm remained evident.
PubMed: 38681433
DOI: 10.7759/cureus.57158 -
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 -
Journal of Hematology Apr 2024Intracerebral hemorrhage is a potentially fatal complication in patients with acute leukemia and contributing factors include thrombocytopenia and coagulopathy. Patients...
Intracerebral hemorrhage is a potentially fatal complication in patients with acute leukemia and contributing factors include thrombocytopenia and coagulopathy. Patients with acute leukemia may develop subdural hematoma (SDH) spontaneously or secondary to trauma. In patients with acute leukemia and SDH, the surgical evacuation of the hematoma causes significant morbidity and mortality. New approaches and strategies to reduce the need for surgical evacuation are needed to improve outcomes in patients with acute leukemia and intracerebral hemorrhage. We report two cases of acute SDH in patients with acute leukemia successfully treated with middle meningeal artery embolization, a minimally invasive interventional radiology technique, obviating the need for a surgical intervention. The first patient with acute promyelocytic leukemia (APL) presented with coagulopathy and developed an acute SDH after a fall. The second patient with acute myeloid leukemia presented with gum bleeding and also sustained an acute SDH after a fall. Both patients underwent middle meningeal artery embolization for treating their SDHs while actively receiving induction chemotherapy for acute leukemia. Both patients had resolution of their acute SDH and are in remission from their acute leukemia. Middle meningeal artery embolization is a very effective, and within the context of this setting, a novel, minimally invasive technique for management of SDH in acute leukemia patients, which can prevent the need for surgical interventions with its associated comorbidities and high risk of fatal outcomes in patients with acute leukemia and acute SDH.
PubMed: 38644984
DOI: 10.14740/jh1215 -
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 -
EJHaem Feb 2024Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder classically presenting with cytopenia and recurrent infections but atypical manifestations such as bone...
Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder classically presenting with cytopenia and recurrent infections but atypical manifestations such as bone lesions, skin lesions and effusion have been described. We report here an unusual meningeal localization in a 33 years old man who presented with headache, hand paresthesia and visual symptoms. Brain magnetic resonance imaging revealed an occipital meningeal lesion. Diagnostic explorations led to the diagnosis of classical HCL with meningeal localization. After treatment by cladribine and rituximab the patient rapidly improved and is still in complete remission 12 months after end of treatment. The literature review identified 9 other cases of HCL with central nervous system localization (CNS) presenting with brain parenchyma and/or meninges localization. Four out of 9 patients presented with hyperleukocytosis. Most patients experienced good responses with various treatments. Cladribine alone or with rituximab led to complete responses similar to our patient. In our patient, molecular biology revealed KLF2 mutations, which implication in the atypical localization could be suspected but would need dedicated studies. In conclusion, CNS localizations of HCL are rare but can be observed and treatment with cladribine alone or with rituximab appears as an effective strategy.
PubMed: 38406549
DOI: 10.1002/jha2.841 -
Journal of Neuroendovascular Therapy 2024We describe a patient with leukemia-related chronic subdural hematoma (CSDH) who was successfully treated using the combination of surgical evacuation and middle...
OBJECTIVE
We describe a patient with leukemia-related chronic subdural hematoma (CSDH) who was successfully treated using the combination of surgical evacuation and middle meningeal artery (MMA) embolization.
CASE PRESENTATION
A 73-year-old man without apparent head trauma history was admitted to our hospital because of acute myeloid leukemia (AML). Head CT on admission revealed mild CSDH on both sides. Medical treatment options, including chemotherapy, were started. Since a decrease in platelet count and disseminated intravascular coagulation were observed on day 4, recombinant thrombomodulin was administered. As the patient exhibited signs of altered consciousness due to the enlargement of the right CSDH on day 10, we performed surgical drainage. Despite subsequent platelet transfusion and administration of goreisan, the right CSDH recurred within a short period. On day 17, we performed the second surgery and MMA embolization in one stage. The postoperative clinical course was favorable without recurrence of the hematoma. The patient eventually died on day 123 from a deterioration of his general condition.
CONCLUSION
Although MMA embolization has recently been recognized as an effective treatment option for recurrent CSDH, there are no published reports addressing the efficacy of MMA embolization for refractory CSDH associated with hematological malignancies. Findings from the management of this case suggest that MMA embolization can be the effective treatment option for CSDH in patients with severe hemorrhagic diathesis due to AML.
PubMed: 38384392
DOI: 10.5797/jnet.cr.2023-0084 -
British Journal of Cancer Apr 2024Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest...
BACKGROUND
Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest ever cohort.
METHODS
Using data from 69,460 5-year childhood cancer survivors (diagnosed 1940-2008), across Europe, standardized incidence ratios (SIRs) and cumulative incidence were calculated.
RESULTS
In total, 279 glioma and 761 meningioma were identified. CNS tumour (SIR: 16.2, 95% CI: 13.7, 19.2) and leukaemia (SIR: 11.2, 95% CI: 8.8, 14.2) survivors were at greatest risk of glioma. The SIR for CNS tumour survivors was still 4.3-fold after age 50 (95% CI: 1.9, 9.6), and for leukaemia survivors still 10.2-fold after age 40 (95% CI: 4.9, 21.4). Following cranial radiotherapy (CRT), the cumulative incidence of a glioma in CNS tumour survivors was 2.7%, 3.7% and 5.0% by ages 40, 50 and 60, respectively, whilst for leukaemia this was 1.2% and 1.7% by ages 40 and 50. The cumulative incidence of a meningioma after CRT in CNS tumour survivors doubled from 5.9% to 12.5% between ages 40 and 60, and in leukaemia survivors increased from 5.8% to 10.2% between ages 40 and 50.
DISCUSSION
Clinicians following up survivors should be aware that the substantial risks of meningioma and glioma following CRT are sustained beyond age 40 and be vigilant for symptoms.
Topics: Humans; Adolescent; Adult; Middle Aged; Meningioma; Risk Factors; Neoplasms, Second Primary; Central Nervous System Neoplasms; Glioma; Survivors; Leukemia; Europe; Meningeal Neoplasms; Incidence
PubMed: 38243010
DOI: 10.1038/s41416-024-02577-y