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Laboratory Medicine Sep 2023Primary amebic meningoencephalitis (PAM) is a fulminant fatal human disease caused by the free-living amoeba Naegleria fowleri. Infection occurs after inhalation of... (Review)
Review
Primary amebic meningoencephalitis (PAM) is a fulminant fatal human disease caused by the free-living amoeba Naegleria fowleri. Infection occurs after inhalation of water containing the amoeba, typically after swimming in bodies of warm freshwater. N. fowleri migrates to the brain where it incites meningoencephalitis and cerebral edema leading to death of the patient 7 to 10 days postinfection. Although the disease is rare, it is almost always fatal and believed to be underreported. The incidence of PAM in countries other than the United States is unclear and possibly on track to being an emerging disease. Poor prognosis is caused by rapid progression, suboptimal treatment, and underdiagnosis. As diagnosis is often performed postmortem and testing is only performed by a few laboratories, more accessible testing is necessary. This article reviews the current methods used in the screening and confirmation of PAM and makes recommendations for improved diagnostic practices and awareness.
Topics: Humans; United States; Central Nervous System Protozoal Infections; Brain; Meningoencephalitis; Naegleria fowleri; Clinical Laboratory Techniques; Amebiasis
PubMed: 36638160
DOI: 10.1093/labmed/lmac158 -
The Pediatric Infectious Disease Journal Apr 2024Seroprevalence studies have shown that 70% of children are exposed to Cryptococcus , the most common cause of meningitis in people living with human immunodeficiency...
BACKGROUND
Seroprevalence studies have shown that 70% of children are exposed to Cryptococcus , the most common cause of meningitis in people living with human immunodeficiency virus (HIV), but reported pediatric disease prevalence is much lower than in adults.
METHODS
PubMed and Ovid Global Health databases were searched with the terms "cryptococcosis," "cryptococcal meningitis," " Cryptococcus neoformans " or " Cryptococcus gattii ." All studies reporting pediatric specific data in the English language from 1980 up until December 2022 were included.
RESULTS
One hundred sixty-eight publications were reviewed totaling 1469 children, with the majority reported from Africa (54.2%). Sixty-five percent (961) were HIV positive, 10% (147) were non-HIV immunocompromised and 19% (281) were immunocompetent. Clinical signs and symptoms were only reported for 458 children, with fever (64%), headache (55%) and vomiting (39%) being the most common. Most children (80%) suffered from meningoencephalitis. Lung involvement was rarely described in HIV-positive children (1%), but significantly more common in the non-HIV immunocompromised (36%) and immunocompetent (40%) groups ( P < 0.0001). Only 22% received the recommended antifungal combination therapy, which was significantly higher in immunocompetent children than those with HIV (39% vs. 6.8%; P < 0.0001). Overall mortality was 23%. A significant higher mortality was observed in children with HIV compared with immunocompetent children (32% vs. 16%; P < 0.001), but not compared with children with non-HIV immunosuppression (25).
CONCLUSIONS
This is the largest review of pediatric cryptococcosis with new observations on differences in clinical presentation and outcome depending on the underlying condition. The lack of granular clinical data urges prospective clinical epidemiological studies for improved insight in the epidemiology, management and outcome of cryptococcosis in children.
Topics: Adult; Humans; Child; Prospective Studies; Seroepidemiologic Studies; Cryptococcosis; Cryptococcus neoformans; HIV Seropositivity
PubMed: 38241632
DOI: 10.1097/INF.0000000000004216 -
Pathogens (Basel, Switzerland) Oct 2023Cryptococcosis is an invasive fungal infection found worldwide that causes significant morbidity and mortality among a broad range of hosts. There are approximately... (Review)
Review
Cryptococcosis is an invasive fungal infection found worldwide that causes significant morbidity and mortality among a broad range of hosts. There are approximately 223,000 new cases of cryptococcosis annually throughout the world, and at least 180,000 deaths are attributed to this infection each year. Most of these are due to complications of cryptococcal meningoencephalitis among HIV-infected patients in resource-limited environments. The majority of individuals diagnosed with cryptococcosis have underlying conditions associated with immune dysfunction such as HIV, solid organ transplant, hematologic malignancy, organ failure syndromes, and/or the use of immunosuppressive agents such as glucocorticosteroids and biologic agents. In most clinical series, there is a small proportion of patients with cryptococcosis who are phenotypically normal; that is, they have no clinically obvious predisposition to disease. Cryptococcal meningoencephalitis (CME) presentation and management differ substantially between these normal individuals and their immunocompromised counterparts. In this review, we will focus on CME in the phenotypically normal host and underscore differences in the clinical presentation, management, outcome, and potential risk factors for these patients compared to immunocompromised persons who develop this potential devastating invasive fungal infection.
PubMed: 38003768
DOI: 10.3390/pathogens12111303 -
Journal of Neuroimmunology Aug 2023Anti-N-methyl-d-aspartate receptor autoimmune encephalitis (NMDAR AE) is an antibody-mediated neurological disorder that may be caused by post-herpes simplex virus-1...
Anti-N-methyl-d-aspartate receptor autoimmune encephalitis (NMDAR AE) is an antibody-mediated neurological disorder that may be caused by post-herpes simplex virus-1 meningoencephalitis (HSV ME) and ovarian teratomas, although most pediatric cases are idiopathic. We sought to evaluate if other infections precede NMDAR AE by conducting a single-center, retrospective, case-control study of 86 pediatric cases presenting to Texas Children's Hospital between 2006 and 2022. HSV ME (HSV-1 and HSV-2) was a significantly more common preceding infection in the experimental group compared to control patients with idiopathic intracranial hypertension, while there was no difference in remote HSV infection between the two groups. Recent Epstein-Barr virus infection was evident in 8/42 (19%) tested experimental patients in comparison to 1/25 (4%) tested control patients which provided evidence for a genuine measure of effect but was not statistically significant due to small sample size (p = 0.07). The other 25 infectious etiologies were not different among the two groups and not all variables were clinically indicated or obtained in every subject, highlighting the need for future standardized, multi-institutional studies on underlying infectious precursors of autoimmune encephalitis.
PubMed: 37364517
DOI: 10.1016/j.jneuroim.2023.578139 -
Archives of Virology Sep 2023In recent years, enterovirus A71 (EV-A71) infection has become a major global public health problem, especially for infants and young children. The results of... (Review)
Review
In recent years, enterovirus A71 (EV-A71) infection has become a major global public health problem, especially for infants and young children. The results of epidemiological research show that EV-A71 infection can cause acute hand, foot, and mouth disease (HFMD) and complications of the nervous system in severe cases, including aseptic pediatric meningoencephalitis, acute flaccid paralysis, and even death. Many studies have demonstrated that EV-A71 infection may trigger a variety of intercellular and intracellular signaling pathways, which are interconnected to form a network that leads to the innate immune response, immune escape, inflammation, and apoptosis in the host. This article aims to provide an overview of the possible mechanisms underlying infection, signaling pathway activation, the immune response, immune evasion, apoptosis, and the inflammatory response caused by EV-A71 infection and an overview of potential therapeutic strategies against EV-A71 infection to better understand the pathogenesis of EV-A71 and to aid in the development of antiviral drugs and vaccines.
Topics: Infant; Child; Humans; Child, Preschool; Enterovirus; Hand, Foot and Mouth Disease; Enterovirus Infections; Immunity, Innate; Inflammation; Enterovirus A, Human
PubMed: 37773227
DOI: 10.1007/s00705-023-05882-8 -
Clinical Infectious Diseases : An... Jan 2024Powassan virus (POWV) is an emerging arthropod-borne flavivirus, transmitted by Ixodes spp. ticks, which has been associated with neuroinvasive disease and poor outcomes.
BACKGROUND
Powassan virus (POWV) is an emerging arthropod-borne flavivirus, transmitted by Ixodes spp. ticks, which has been associated with neuroinvasive disease and poor outcomes.
METHODS
A retrospective study was conducted at Mayo Clinic from 2013 to 2022. We included clinical and epidemiologic data of probable and confirmed neuroinvasive POWV cases.
RESULTS
Sixteen patients with neuroinvasive POWV were identified; their median age was 63.2 years, and 62.5% were male. Six patients presented with rhombencephalitis, 4 with isolated meningitis, 3 with meningoencephalitis, 2 with meningoencephalomyelitis, and 1 with opsoclonus myoclonus syndrome. A median time of 18 days was observed between symptom onset and diagnosis. Cerebrospinal fluid analysis showed lymphocytic pleocytosis with elevated protein and normal glucose in the majority of patients. Death occurred within 90 days in 3 patients (18.8%), and residual neurologic deficits were seen in 8 survivors (72.7%).
CONCLUSIONS
To our knowledge, this is the largest case series of patients with neuroinvasive POWV infection. We highlight the importance of a high clinical suspicion among patients who live in or travel to high-risk areas during the spring to fall months. Our data show high morbidity and mortality rates among patients with neuroinvasive disease.
Topics: Animals; Humans; Male; Middle Aged; Female; Encephalitis Viruses, Tick-Borne; Retrospective Studies; Encephalitis, Tick-Borne; Meningoencephalitis; Ixodes
PubMed: 37540989
DOI: 10.1093/cid/ciad454 -
European Journal of Neurology Aug 2023Outcome and rechallenge data on central nervous system (CNS) autoimmunity triggered by immune checkpoint inhibitors (ICIs) are limited. We aim to describe a large series...
BACKGROUND AND PURPOSE
Outcome and rechallenge data on central nervous system (CNS) autoimmunity triggered by immune checkpoint inhibitors (ICIs) are limited. We aim to describe a large series of patients with ICI-triggered CNS autoimmunity, and to compare these patients with spontaneous paraneoplastic syndromes (PNS).
METHODS
We retrospectively reviewed Mayo Clinic patients with ICI-triggered CNS autoimmunity (February 2015-June 2021). Clinical characteristics were compared to spontaneous PNS patients (with antineuronal nuclear antibody [ANNA]-1 or anti-Hu neurological autoimmunity, and/or neuroendocrine tumors [NET]) evaluated within the same period.
RESULTS
Thirty-one patients were included (55% female, median age = 63 years, range = 39-76). Median time from ICI initiation was 3.65 months (range = 0.8-44.5). The most common associated malignancies were melanoma and small cell lung cancer. CNS manifestations included encephalitis (n = 16), meningoencephalitis (n = 8), cerebellar ataxia (n = 4), demyelinating syndrome (n = 2), and myelopathy (n = 1). Magnetic resonance imaging was abnormal in 62%. Cerebrospinal fluid was inflammatory in 70%. Neural autoantibodies were identified in 47%, more frequently in patients with NET (p = 0.046). ICI was discontinued in 97%; 90% received immunosuppressive treatment. After median 6.8 months follow-up (range = 0.7-46), 39% had unfavorable outcomes (grade ≥ 3). This was associated with higher severity degree at onset, shorter period from ICI to neurological symptom onset, and encephalitis. Four patients were rechallenged with ICI, and one relapsed. Patients with NET and with ANNA-1 ICI-triggered CNS autoimmunity had associated peripheral nervous system manifestations more frequently than their spontaneous counterparts (p = 0.007 and p = 0.028, respectively).
CONCLUSIONS
One third of ICI-related CNS autoimmunity patients have unfavorable outcomes. Relapses may occur after ICI rechallenge. Neural autoantibodies are often present, more commonly in patients with NET.
Topics: Humans; Female; Adult; Middle Aged; Aged; Male; Autoimmunity; Immune Checkpoint Inhibitors; Retrospective Studies; Neoplasms; Autoantibodies; Encephalitis; Central Nervous System
PubMed: 37151179
DOI: 10.1111/ene.15835 -
Antimicrobial Agents and Chemotherapy Oct 2023() is an encapsulated neurotropic fungal pathogen and the causative agent of cryptococcal meningoencephalitis (CME) in humans. Recommended treatment for CME is...
() is an encapsulated neurotropic fungal pathogen and the causative agent of cryptococcal meningoencephalitis (CME) in humans. Recommended treatment for CME is Amphotericin B (AmpB) and 5-fluorocytosine (5-FC). Though effective, AmpB has displayed numerous adverse side effects due to its potency and nephrotoxicity, prompting investigation into alternative treatments. Palmitoylethanolamide (PEA) is an immunomodulatory compound capable of promoting neuroprotection and reducing inflammation. To investigate the efficacy of PEA as a therapeutic alternative for CME, we intracerebrally infected mice with and treated them with PEA or AmpB alone or in combination. Our results demonstrate that PEA alone does not significantly prolong survival nor reduce fungal burden, but when combined with AmpB, PEA exerts an additive effect and promotes both survivability and fungal clearance. However, we compared this combination to traditional AmpB and 5-FC treatment in a survivability study and observed lower efficacy. Overall, our study revealed that PEA alone is not effective as an antifungal agent in the treatment of CME. Importantly, we describe the therapeutic capability of PEA in the context of infection and show that its immunomodulatory properties may confer limited protection when combined with an effective fungicidal agent.
Topics: Humans; Mice; Animals; Meningitis, Cryptococcal; Antifungal Agents; Cryptococcus neoformans; Cryptococcosis; Amphotericin B; Flucytosine; Meningoencephalitis
PubMed: 37750714
DOI: 10.1128/aac.00459-23 -
Practical Neurology Oct 2023Neurological involvement in Behçet's syndrome arises predominately through an inflammatory meningoencephalitis characterised by perivenular inflammation due to... (Review)
Review
Neurological involvement in Behçet's syndrome arises predominately through an inflammatory meningoencephalitis characterised by perivenular inflammation due to activation of Th-17 immunological pathways. The brainstem is involved in 50% of cases, the diencephalon and other areas of the brain in 30%, and the spinal cord in 10%. Movement disorders and epilepsy may occur. Psychiatric syndromes may arise with brain and brainstem involvement, and cognitive disorders relate to the brain disease, to circulating inflammatory factors, and to fatigue and despondency. Eighty per cent of cases begin with a relapsing disease course, of whom 70% have only one attack, and 30% have a progressive disease course either from onset or following an initially relapsing course. Venous thrombosis leading to intracranial hypertension and cerebral venous infarction is less common and caused by inflammation in affected veins and a circulating prothrombotic state. Arterial involvement is rare and relates to an arteritis affecting large-sized and medium-sized vessels within the brain leading to infarction, subarachnoid and parenchymal haemorrhage, aneurysm formation and arterial dissection. There is a newly recognised disorder of cerebral cortical hypoperfusion. Cranial neuropathy, peripheral neuropathy and myositis are rare. There has been significant progress in understanding the pathophysiology and treatment of the systemic disease, leading to improved outcomes, but there has been no randomised trial of treatment in the neurological disorder.
Topics: Humans; Behcet Syndrome; Magnetic Resonance Imaging; Treatment Outcome; Inflammation; Infarction
PubMed: 37775123
DOI: 10.1136/pn-2023-003875