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Cureus May 2024Moyamoya angiopathy is a rare cerebrovascular condition characterized by insufficient cerebral blood flow resulting from arterial vessel narrowing or occlusion,...
Moyamoya angiopathy is a rare cerebrovascular condition characterized by insufficient cerebral blood flow resulting from arterial vessel narrowing or occlusion, potentially leading to cerebral ischemia due to inadequate oxygen and nutrient supply to the brain tissue. The development of collateral vessels in stenotic regions, inherently fragile and prone to rupture, may further precipitate intracerebral hemorrhage. Alongside focal neurological symptoms, the common clinical presentations of Moyamoya angiopathy encompass headaches, dizziness, cognitive impairments, seizures, and involuntary movements. When associated with an underlying systemic illness, including Down Syndrome, cranial radiation, neurofibromatosis type 1, or meningitis, the condition is termed Moyamoya syndrome; whereas when idiopathic and a genetic mutation are identified, it is referred to as Moyamoya disease. In this report, we present a case of the rare Moyamoya syndrome, which was attributed to syphilis and HIV infection and was identified during an investigation into the etiology of ischemic stroke in a young patient.
PubMed: 38894803
DOI: 10.7759/cureus.60579 -
Diagnostics (Basel, Switzerland) May 2024(meningococcus) is a Gram-negative bacterium that colonises the nasopharynx of about 10% of the healthy human population. Under certain conditions, it spreads into the...
BACKGROUND
(meningococcus) is a Gram-negative bacterium that colonises the nasopharynx of about 10% of the healthy human population. Under certain conditions, it spreads into the body, causing infections with high morbidity and mortality rates. Although the capsule is the key virulence factor, unencapsulated strains have proved to possess significant clinical implications as well. Meningococcal meningitis is a primarily human infection, with limited animal models that are dependent on a variety of parameters such as bacterial virulence and mouse strain. In this study, we aimed to develop a murine meningitis model to be used in the study of various antimicrobial compounds.
METHOD
We used a capsule-deficient strain that was thoroughly analysed through various methods. The bacterial strain was incubated for 48 h in brain-heart infusion (BHI) broth before being concentrated and injected intracisternally to bypass the blood-brain barrier in CD-1 mice. This prolonged incubation time was a key factor in increasing the virulence of the bacterial strain. A total of three more differently prepared inoculums were tested to further solidify the importance of the protocol (a 24-h incubated inoculum, a diluted inoculum, and an inactivated inoculum). Antibiotic treatment groups were also established. The clinical parameters and number of deaths were recorded over a period of 5 days, and comatose mice with no chance of recovery were euthanised.
RESULTS
The bacterial strain was confirmed to have no capsule but was found to harbour a total of 56 genes coding virulence factors, and its antibiotic susceptibility was established. Meningitis was confirmed through positive tissue culture and histological evaluation, where specific lesions were observed, such as perivascular sheaths with inflammatory infiltrate. In the treatment groups, survival rates were significantly higher (up to 81.25% in one of the treatment groups compared to 18.75% in the control group).
CONCLUSION
We managed to successfully develop a cost-efficient murine (using simple CD-1 mice instead of expensive transgenic mice) meningococcal meningitis model using an unencapsulated strain with a novel method of preparation.
PubMed: 38893642
DOI: 10.3390/diagnostics14111116 -
Diagnostics (Basel, Switzerland) May 2024Meningitis is the infection of the meninges, which are connective tissue membranes covering the brain, and it most commonly affects the leptomeninges. Clinically,... (Review)
Review
Meningitis is the infection of the meninges, which are connective tissue membranes covering the brain, and it most commonly affects the leptomeninges. Clinically, meningitis may present with fever, neck stiffness, altered mental status, headache, vomiting, and neurological deficits. Encephalitis is an infection of the brain, which usually presents with fever, altered mental status, neurological deficits, and seizure. Meningitis and encephalitis are serious conditions which could also coexist, with high morbidity and mortality, thus requiring prompt diagnosis and treatment. Imaging plays an important role in the clinical management of these conditions, especially Magnetic Resonance Imaging. It is indicated to exclude mimics and evaluate the presence of complications. The aim of this review is to depict imaging findings of the most common meningitis and encephalitis.
PubMed: 38893591
DOI: 10.3390/diagnostics14111064 -
International Journal of Molecular... May 2024The ocular glymphatic system subserves the bidirectional polarized fluid transport in the optic nerve, whereby cerebrospinal fluid from the brain is directed along... (Review)
Review
The ocular glymphatic system subserves the bidirectional polarized fluid transport in the optic nerve, whereby cerebrospinal fluid from the brain is directed along periarterial spaces towards the eye, and fluid from the retina is directed along perivenous spaces following upon its axonal transport across the glial lamina. Fluid homeostasis and waste removal are vital for retinal function, making the ocular glymphatic fluid pathway a potential route for targeted manipulation to combat blinding ocular diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Several lines of work investigating the bidirectional ocular glymphatic transport with varying methodologies have developed diverging mechanistic models, which has created some confusion about how ocular glymphatic transport should be defined. In this review, we provide a comprehensive summary of the current understanding of the ocular glymphatic system, aiming to address misconceptions and foster a cohesive understanding of the topic.
Topics: Humans; Glymphatic System; Animals; Optic Nerve; Retina; Eye; Glaucoma
PubMed: 38891923
DOI: 10.3390/ijms25115734 -
Breast Cancer Research and Treatment Aug 2024Leptomeningeal disease (LMD) is a devastating complication of metastatic breast cancer (MBC). It is critical to better understand the risk factors, natural history, and...
PURPOSE
Leptomeningeal disease (LMD) is a devastating complication of metastatic breast cancer (MBC). It is critical to better understand the risk factors, natural history, and treatment outcomes, including patients in a modern cohort.
METHODS
In this single center retrospective cohort study, we identified patients with MBC and LMD who received care from 2000 to 2024 and abstracted key clinical, treatment, and survival data.
RESULTS
We identified 111 patients with MBC and LMD, including patients with the following subtypes: HR+/HER2- (n = 53, 47.7%), HER2+ (n = 30, 27.0%), and triple negative breast cancer (TNBC; n = 28, 25.2%). Median time from the diagnosis of MBC to LMD was 16.4 months (range 0-101.3 months). After the diagnosis of LMD, most patients received systemic therapy (n = 66, 59.5%) and/or central nervous system (CNS)-directed therapy (n = 94, 84.7%) including intrathecal therapy (n = 42, 37.8%) and/or CNS-directed radiation therapy (n = 70, 63.1%). In all patients, median overall survival (OS) from the diagnosis of LMD to death was 4.1 months (range 0.1-78.1 months) and varied by subtype, with HR+/HER2- or HER2+ MBC patients living longer than those with TNBC (4.2 and 6.8 months respectively vs. 2.0 months, p < 0.01, HR 2.15, 95% CI 1.36-3.39). Patients who received CNS-directed therapy lived longer than those who did not (4.2 vs. 1.3, p = 0.02 HR 0.54, 0.32-0.91). Patients diagnosed with LMD from 2015 to 2024 lived longer than those diagnosed from 2000 to 2014 (6.4 vs. 2.9 months, p = 0.04, HR 0.67, 95% CI 0.46-0.99). On multivariable analysis, having TNBC was associated with shorter OS from time of LMD to death (p = 0.004, HR 2.03, 95% CI 1.25-3.30).
CONCLUSION
This is one of the largest case series of patients with MBC and LMD. Patients diagnosed with LMD from 2015 to 2024 lived longer than those diagnosed from 2000 to 2014, although median OS was short overall. Patients with TNBC and LMD had particularly short OS. Novel therapeutic strategies for LMD remain an area of unmet clinical need.
Topics: Humans; Female; Middle Aged; Retrospective Studies; Aged; Adult; Breast Neoplasms; Meningeal Neoplasms; Aged, 80 and over; Meningeal Carcinomatosis; Receptor, ErbB-2; Prognosis
PubMed: 38888796
DOI: 10.1007/s10549-024-07339-1 -
Open Forum Infectious Diseases Jun 2024Several recent randomized trials have been conducted in resource-limited settings for cryptococcal meningitis that have rapidly innovated international guidelines. The...
BACKGROUND
Several recent randomized trials have been conducted in resource-limited settings for cryptococcal meningitis that have rapidly innovated international guidelines. The 2010 Infectious Diseases Society of America (IDSA) cryptococcal meningitis guideline has not been updated with recent trials. The 2022 AMBITION-cm trial found that a single 10-mg/kg dose of liposomal amphotericin B plus daily flucytosine and fluconazole for 2 weeks was noninferior to 1 week of amphotericin B deoxycholate with flucytosine. It is unknown whether physicians in high-resource settings are using this regimen or more traditional regimens.
METHODS
We developed an electronic survey in June 2023 to better understand whether physician members of the IDSA Emerging Infections Network (EIN) and Mycoses Study Group Education and Research Consortium (MSG-ERC) had used the AMBITION-cm induction regimen, would use the regimen in hypothetical clinical scenarios, and what perceived barriers to use existed.
RESULTS
A total of 242 of 561 (43%) physicians responded to the survey, of whom 205 provided care for persons with cryptococcal meningitis in the last year. Overall, 29 (14%) had used the AMBITION-cm regimen, and 176 (86%) had not. In various hypothetical clinical scenarios, only ∼10% of 209 respondents selected the AMBITION-cm regimen as preferred. Perceived barriers to uptake included the applicability of trials performed in low-resource settings to high-resource settings, that the regimen is not recommended in the 2010 IDSA guidelines, and the applicability to persons without HIV.
CONCLUSIONS
Most respondents had not used the single-dose liposomal amphotericin B regimen, but the regimen is being used. Further study of this regimen in other patient populations and settings is necessary.
PubMed: 38887490
DOI: 10.1093/ofid/ofae120 -
Open Forum Infectious Diseases Jun 2024Clinical and epidemiological features of 7 human immunodeficiency virus-negative Peruvian patients coinfected with human T-lymphotropic virus type 1 (HTLV-1) and...
Clinical and epidemiological features of 7 human immunodeficiency virus-negative Peruvian patients coinfected with human T-lymphotropic virus type 1 (HTLV-1) and cryptococcosis (2006-2017) were studied. Most cases had meningeal involvement, were male, and originated from Peru's jungle. Patients with cryptococcosis should be tested for HTLV-1 in endemic areas of this retrovirus.
PubMed: 38887485
DOI: 10.1093/ofid/ofae022 -
Cureus May 2024Lyme disease is a multisystem infectious disease. It is caused by the dissemination of after a tick bite. It has various manifestations across different age groups....
Lyme disease is a multisystem infectious disease. It is caused by the dissemination of after a tick bite. It has various manifestations across different age groups. Commonly involved organs are the skin, joints, and nervous system. Nervous system Lyme disease has a wide spectrum of manifestations. While facial nerve palsy and subacute meningitis are commonly observed in the pediatric population, our case report reveals an uncommon manifestation of the nervous system Lyme disease. A four-year-old patient exhibited mood changes, behavioral issues, and generalized tonic-clonic seizures. Extensive diagnostic workup initially yielded no clear cause until positive IgM and IgG serology for suggested Lyme neuroborreliosis. This differs from the usual symptoms seen in pediatric cases. The patient responded positively to antibiotic treatment, but persistent post-treatment behavioral issues raised questions about potential long-term effects. This case underscores the importance of considering Lyme disease in atypical presentations, even in non-endemic areas, necessitating an adaptable diagnostic approach for improved outcomes, especially in pediatric patients. Continued research into the comprehensive understanding of Lyme disease in pediatric patients is crucial.
PubMed: 38887358
DOI: 10.7759/cureus.60535 -
Neural Regeneration Research Mar 2025Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not...
Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.
PubMed: 38886941
DOI: 10.4103/NRR.NRR-D-23-01595 -
PLOS Global Public Health 2024Tuberculosis (TB) mortality in Zambia remains high at 86 per 100,000 populations, translating to approximately 15,000 TB-related deaths annually. We conducted a...
Tuberculosis (TB) mortality in Zambia remains high at 86 per 100,000 populations, translating to approximately 15,000 TB-related deaths annually. We conducted a nationwide retrospective cohort study to understand predictors, time to death, and probable causes of mortality among persons on TB treatment in Zambia. We reviewed medical records for persons with TB registered in 54 purposively selected hospitals in Zambia between January and December 2019. We fitted a Cox proportional hazards model to identify predictors of mortality. Of the 13,220 records abstracted, 10,987 were analyzed after excluding records of persons who transferred in from other hospitals, those with inconsistent dates and those whose treatment outcome was not evaluated. The majority of persons with TB were men, (61.5%, n = 6,761) with a median age of 36 years (IQR: 27-46 years). Overall, 1,063 (9.7%) died before completing TB treatment (incidence rate = 16.9 deaths per 1,000 person-months). Median age at death was 40 years (IQR: 31-52). The majority of deaths (75.7%, n = 799) occurred in the first two months of TB treatment, with a median time to death of 21 days (IQR: 6-57). Independent risk factors for TB mortality included age >54 years, being treated in Eastern, Southern, Western, Muchinga and Central provinces, receiving treatment from a third-level or mission hospital, methods of diagnosis other than Xpert MTB/RIF, extrapulmonary TB (EPTB), and positive HIV status. Probable causes of death were septic shock (18.8%), TB Immune Reconstitution Inflammatory Syndrome (TB IRIS) (17.8%), end-organ damage (13.4%), pulmonary TB (11.4%), anemia (9.6%) and TB meningitis (7.8%). These results show high mortality among people undergoing TB treatment in Zambia. Interventions targeted at persons most at risk such as the elderly, those with EPTB, and those living with HIV, can help reduce TB-related mortalities in Zambia.
PubMed: 38885238
DOI: 10.1371/journal.pgph.0003329