Early Neonatal Presentation and Neuroimaging of Parechovirus Meningoencephalitis in a Preterm Baby: A Case Report.

Neonatal meningoencephalitis caused by human parechovirus infection is being increasingly recognized in recent literature. While most cases are postnatally acquired, intrauterine infection is rare, presents early and has a more severe impact on brain health and development. We discuss here an infant born preterm at 34 weeks gestational age, with neonatal course remarkable for severe encephalopathy presenting on day 2 of life due to human parechovirus meningoencephalitis transmitted in utero. Early magnetic resonance brain imaging detected extensive white matter injury and subsequently evolved into multicystic leukoencephalopathy. Posthospital discharge, infant was noted to have early neurodevelopmental impairment at 4 months corrected age.

Persistent hypernatremia secondary to adipsic central diabetes insipidus in a patient with herpes-induced meningoencephalitis and COVID-19 infection: a case report.

Central diabetes insipidus (CDI) typically manifests as a polyuria-polydipsia syndrome, in which normonatremia is generally maintained through the polydipsia. A 53-year-old woman presented with diabetic ketosis and hyperosmolar hyperglycemic syndrome. Her medical history included herpes meningoencephalitis, which was associated with confusion and amnesia. On physical examination, she was apyretic, confused, and had signs of extracellular dehydration. Her capillary glucose concentration was high and her urine was positive for ketones. Laboratory investigations revealed severe hyperglycemia, hypernatremia (plasma hyperosmolarity of 393.6 mOsm/L), and mild acute renal failure. In addition, she had a paucisymptomatic COVID-19 infection. Intravenous rehydration with isotonic saline solution and insulin therapy were effective at controlling the ketosis and ameliorating the hyperglycemia, but failed to normalize the hypernatremia and hyperosmolarity. She was not thirsty and had a urine output of 1 L/day, with urinary hypotonicity. Desmopressin administration reduced the hypernatremia and hyperosmolarity to within their normal ranges, and the patient's urinary osmolarity increased to 743 mOsm/L. Therefore, adipsic CDI was diagnosed. Endocrine investigations revealed isolated central hypothyroidism. The results of pituitary magnetic resonance imaging were normal. Thus, patients with impaired thirst may have an atypical presentation of CDI. In addition, the diagnosis of adipsic CDI is particularly challenging.

[Listeria meningoencephalitis resulting in complete bilateral ophtalmoplegia and locked-in syndrome]. / Listerioznyi meningoentsefalit s razvitiem polnoi dvustoronnei oftal'moplegii i sindroma «zapertogo cheloveka¼.

This is a description of the case of quite severe neurolisteriosis in an adult man resulting in the rare combination of neurological symptoms such as complete bilateral ophtalmoplegia and locked-in syndrome. The case illustrates clinical features that are special for this disorder and also highlights management of such patients.

Borna disease in an adult free-ranging Eurasian beaver (Castor fiber albicus).

Borna disease (BD) associated with a peracute bacterial septicaemia with Escherichia coli was diagnosed in an adult female, naturally infected, free-ranging Eurasian beaver of the subspecies Castor fiber albicus, clinically characterized by weight loss, depression, weakness and gurgled peristaltic sounds. The beaver was euthanized humanely. Necropsy and light microscopy revealed a non-purulent meningoencephalitis with typical mononuclear perivascular cuffs and parenchymal infiltrates. The diagnosis of BD was confirmed by detection of viral antigen and RNA by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). The PCR product was sequenced and cluster analysis revealed a close relationship between endemic clusters in Saxony-Anhalt. This is the first report of naturally occurring BD in a free-ranging Eurasian beaver.

New insights into neuropathology and pathogenesis of autoimmune glial fibrillary acidic protein meningoencephalomyelitis.

Anti-glial fibrillary acidic protein (GFAP) meningoencephalomyelitis (autoimmune GFAP astrocytopathy) is a new autoimmune central nervous system (CNS) disease diagnosable by the presence of anti-GFAP autoantibodies in the cerebrospinal fluid and presents as meningoencephalomyelitis in the majority of patients. Only few neuropathological reports are available and little is known about the pathogenic mechanisms. We performed a histopathological study of two autopsies and nine CNS biopsies of patients with anti-GFAP autoantibodies and found predominantly a lymphocytic and in one autopsy case a granulomatous inflammatory phenotype. Inflammatory infiltrates were composed of B and T cells, including tissue-resident memory T cells. Although obvious astrocytic damage was absent in the GFAP-staining, we found cytotoxic T cell-mediated reactions reflected by the presence of CD8+/perforin+/granzyme A/B+ cells, polarized towards astrocytes. MHC-class-I was upregulated in reactive astrocytes of all biopsies and two autopsies but not in healthy controls. Importantly, we observed a prominent immunoreactivity of astrocytes with the complement factor C4d. Finally, we provided insight into an early phase of GFAP autoimmunity in an autopsy of a pug dog encephalitis that was characterized by marked meningoencephalitis with selective astrocytic damage with loss of GFAP and AQP4 in the lesions.Our histopathological findings indicate that a cytotoxic T cell-mediated immune reaction is present in GFAP autoimmunity. Complement C4d deposition on astrocytes could either represent the cause or consequence of astrocytic reactivity. Selective astrocytic damage is prominent in the early phase of GFAP autoimmunity in a canine autopsy case, but mild or absent in subacute and chronic stages in human disease, probably due to the high regeneration potential of astrocytes. The lymphocytic and granulomatous phenotypes might reflect different stages of lesion development or patient-specific modifications of the immune response. Future studies will be necessary to investigate possible implications of pathological subtypes for clinical disease course and therapeutic strategies.

Causes and prognosis of adults experiencing a first seizure in adulthood: A pilot cohort study conducted in five countries in Latin America.

There are limited data on first seizure (FS) among adults in low and middle-income countries. We describe findings from a prospective cohort study involving 180 adults presenting with seizures in emergency departments in five Latin American countries. Overall, 102 participants (56.7%) had acute symptomatic seizures (ASyS) while 78 (43.3%) had unprovoked seizures (UPS). Among patients with ASyS, 55 (53.9%) had structural causes, with stroke (n = 24, 23.5%), tumor (n = 10, 9.8%), and trauma (n = 3, 3%) being the most frequent. Nineteen patients (18.6%) had infectious causes, including four (4%) with meningoencephalitis, three (3%) neurocysticercosis, and two (2%) bacterial meningoencephalitis. Twenty patients (19.6%) had metabolic/toxic evidence, including four (4%) with uremic encephalopathy, two (2%) hyponatremia, and three (3%) acute alcohol intoxication. Immune dysfunction was present in seven (7%) patients and neurodegenerative in two (2%). Among participants with UPS, 45 (57.7%) had unknown etiology, 24 (30.7%) had evidence of structural disorders (remote symptomatic), four (5%) were related to infectious etiology (>7 days before the seizure), and five (6.4%) had genetic causes. During the 3- and 6-month follow-up, 29.8% and 14% of patients with UPS, respectively, experienced seizure recurrence, while 23.9% and 24.5% of patients with ASyS had seizure recurrence. Longer follow-up is necessary to assess seizure recurrence for patients with ASyS after the acute cause is resolved and to determine the 10-year risk of recurrence, which is part of the definition of epilepsy. PLAIN LANGUAGE SUMMARY: We monitored 180 adults who presented with their first seizure in emergency departments across five Latin American countries. Among these patients, 57% had acute symptomatic seizures, with structural causes such as stroke (23%), infection (17%), or tumor (10%) being more prevalent. Among the 43% with unprovoked seizures, 58% showed no identifiable acute cause, while 6.4% were due to genetics. Within 3 months after their initial seizure, 26.6% of individuals experienced a second seizure, with 11.9% continuing to have seizures in Months 3-6. Between Months 3 and 6, an additional 20% of patients encountered a second seizure. Research is needed to better understand the cause and prognosis of these patients to improve outcomes.

Batf3-dependent orchestration of the robust Th1 responses and fungal control during cryptococcal infection, the role of cDC1.

While type I conventional dendritic cells (cDC1s) are vital for generating adaptive immunity against intracellular pathogens and tumors, their role in defense against fungal pathogen Cryptococcus neoformans remains unclear. We investigated the role of the cDC1 subset in a fungus-restricting mouse model of cryptococcal infection. The cDC1 subset displayed a unique transcriptional signature with highly upregulated T-cell recruitment, polarization, and activation pathways compared to other DC subsets. Using Batf3-/- mice, which lack the cDC1 population, our results support that Batf3-dependent cDC1s are pivotal for the development of the effective immune response against cryptococcal infection, particularly within the lung and brain. Deficiency in Batf3 cDC1 led to diminished CD4 accumulation and decreased IFNγ production across multiple organs, supporting that cDC1s are a major driver of potent Th1 responses during cryptococcal infection. Consistently, mice lacking Batf3-cDC1 demonstrated markedly diminished fungicidal activity and weaker containment of the fungal pathogen. In conclusion, Batf3-dependent cDC1 can function as a linchpin in mounting Th1 response, ensuring effective fungal control during cryptococcal infection. Harnessing cDC1 pathways may present a promising strategy for interventions against this pathogen.IMPORTANCECryptococcus neoformans causes severe meningoencephalitis, accounting for an estimated 200,000 deaths each year. Central to mounting an effective defense against these infections is T-cell-mediated immunity, which is orchestrated by dendritic cells (DCs). The knowledge about the role of specific DC subsets in shaping anti-cryptococcal immunity is limited. Here, we demonstrate that Batf3 cDC1s are important drivers of protective Th1 CD4 T-cell responses required for clearance of cryptococcal infection. Deficiency of Batf3 cDC1 in the infected mice leads to significantly reduced Th1 response and exacerbated fungal growth to the point where depleting the remaining CD4 T cells no longer affects fungal burden. Unveiling this pivotal role of cDC1 in antifungal defense is likely to be important for the development of vaccines and therapies against life-threatening fungal pathogens.

[Clinical features and pathogenesis of Glial fibrillary acidic protein (GFAP) antibody-associated disorders].

Glial fibrillary acidic protein (GFAP) antibody-associated disorders (AD) were recently proposed to be immune-mediated neurological disorders. The pathogenesis of GFAP antibody-AD is poorly understood. Pathologically, there is a marked infiltration of large numbers of lymphocytes, including CD8+ and CD4+ T cells, into the meningeal and brain parenchyma, especially around the perivascular areas. GFAP-specific cytotoxic T cells are considered to be the effector cells of GFAP antibody-AD. The common phenotype of GFAP antibody-AD includes meningoencephalitis with or without myelitis. During the clinical disease course, patients present with consciousness disturbances, urinary dysfunction, movement disorders, meningeal irritation, and cognitive dysfunction. The detection of GFAP antibodies in the cerebrospinal fluid (CSF) by cell-based assay is essential for a diagnosis of GFAP antibody-AD. The CSF can be examined for lymphocyte-predominant pleocytosis and elevated protein levels. Brain linear perivascular radial enhancement patterns are observed in about half of GFAP antibody-AD patients. Spinal cord magnetic resonance imaging is used to detect longitudinal extensive spinal cord lesions. Although corticosteroid therapy is generally effective, some patients have a poor prognosis and relapse.

C-reactive protein concentration has limited value in the diagnosis of meningoencephalitis of unknown origin in dogs.

OBJECTIVES: To evaluate blood and cerebrospinal fluid (CSF) concentrations of C-reactive protein (CRP) in dogs with meningoencephalitis of unknown origin (MUO); to evaluate whether blood CRP concentration is associated with epidemiological, clinicopathologic, and MRI findings; and to investigate blood CRP predictive power in survival. ANIMALS: 30 client-owned dogs with MUO, 15 client-owned dogs with steroid-responsive meningitis arteritis (SRMA; positive control group), and 15 healthy dogs (negative control group). METHODS: Blood CRP concentration was measured in each group, while it was performed in CSF only in the MUO and SRMA groups. The analysis of epidemiological data included breed, age, sex, duration of clinical signs, and history of seizures. Blinded analysis of MRI was performed based on a classification grid, and traditional CSF analysis parameters were assessed. The predictive power of blood CRP concentration regarding survival at 6 months was investigated. RESULTS: Of the 30 dogs with MUO, 9 (30%) had an increased CRP concentration in blood, and 3 (10%) showed a measurable CRP in CSF. Median blood CRP concentration in dogs with MUO was 0.1 mg/L (range, 0.1 to 102 mg/L), which was not statistically different from the healthy dog group but significantly lower than the SRMA control group. Only the duration of clinical signs was positively associated with an increased blood CRP level. Blood CRP concentration was not associated with survival at 6 months. CLINICAL RELEVANCE: Blood CRP concentration is of limited value for the diagnosis and prognosis of dogs with MUO. Chronicity of the disease may be associated with an increased concentration of blood CRP.

Host-microbe interactions at the blood-brain barrier through the lens of induced pluripotent stem cell-derived brain-like endothelial cells.

Microbe-induced meningoencephalitis/meningitis is a life-threatening infection of the central nervous system (CNS) that occurs when pathogens are able to cross the blood-brain barrier (BBB) and gain access to the CNS. The BBB consists of highly specialized brain endothelial cells that exhibit specific properties to allow tight regulation of CNS homeostasis and prevent pathogen crossing. However, during meningoencephalitis/meningitis, the BBB fails to protect the CNS. Modeling the BBB remains a challenge due to the specialized characteristics of these cells. In this review, we cover the induced pluripotent stem cell-derived, brain-like endothelial cell model during host-pathogen interaction, highlighting the strengths and recent work on various pathogens known to interact with the BBB. As stem cell technologies are becoming more prominent, the stem cell-derived, brain-like endothelial cell model has been able to reveal new insights in vitro, which remain challenging with other in vitro cell-based models consisting of primary human brain endothelial cells and immortalized human brain endothelial cell lines.

Case Report: A Series of Three Meningoencephalitis Cases Caused by Acanthamoeba spp. from Eastern India.

Acanthamoeba spp. are rare etiological agents of meningoencephalitis with high mortality. We present three cases of Acanthamoeba meningoencephalitis in immunocompetent individuals from Eastern India. The first patient presented with fever and headache; the second with headache, visual disturbance, and squint; and the third presented in a drowsy state. The cases presented on March 3, 18, and 21, 2023 respectively. The first two patients had concomitant tubercular meningitis for which they received antitubercular therapy and steroid. Their cerebrospinal fluid showed slight lymphocytic pleocytosis and increased protein. The diagnosis was done by microscopy, culture, and polymerase chain reaction. They received a combination therapy comprising rifampicin, fluconazole, and trimethoprim-sulfamethoxazole. The first patient additionally received miltefosine. She responded well to therapy and survived, but the other two patients died despite intensive care. Detection of three cases within a period of 1 month from Eastern India is unusual. It is imperative to sensitize healthcare providers about Acanthamoeba meningoencephalitis to facilitate timely diagnosis and treatment of the disease.

Monkeypox virus-associated meningoencephalitis diagnosed by detection of intrathecal antibody production.

BACKGROUND: In the 2022 mpox-outbreak most patients presented with mild symptoms. Central nervous system (CNS) involvement has previously been described as a rare and severe complication of mpox; however, diagnostic findings in cerebrospinal fluid (CSF) analysis and neuroimaging studies have only been reported in one case previously. CASE PRESENTATION: We report a previously healthy 37-year-old man with mpox complicated by encephalitis. He first presented with painful skin lesions and genital ulcers; polymerase chain reaction (PCR) from the lesions was positive for mpox. Twelve days later he was admitted with fever and confusion. Neuroimaging and CSF analysis indicated encephalitis. The CSF was PCR-negative for monkeypox virus but intrathecal antibody production was detected. He spontaneously improved over a few days course and recovered fully. CONCLUSIONS: This case of mpox-associated encephalitis shows that CNS involvement in mpox infection may have a relatively mild clinical course, and that detection of intrathecal antibody production can be used to establish the diagnosis if CSF monkeypox virus-PCR is negative.

Spinal cord infarction: a rare but serious complication of pneumococcal meningoencephalitis.

Here, we report the case of a woman in her 40s who came with pyogenic meningitis and infarcts in the brain. While on treatment with antibiotics, she developed new-onset weakness involving bilateral lower limbs and one upper limb 2 weeks into the course of illness. MRI of the spine showed an infarct in the spinal cord. Spinal cord infarction as a complication of pyogenic meningitis is not well recognised unlike tuberculosis meningitis. Unlike ischaemic strokes where thrombolysis is done, for stroke related to infections, there are no definite strategies. Our patient was treated with physiotherapy, continued on antibiotics and slowly recovered over months and at 18-month follow-up, she was walking with a walker. The exact mechanism of thrombosis is not known but may be due to inflammation of the arterial wall and activation of the procoagulant cascade by infection-triggered inflammation. Spinal cord infarction can occur at any phase of the infection and may occur despite appropriate response to antibiotic treatments.

Disseminated cryptococcosis in a patient with idiopathic CD4 + T lymphocytopenia presenting as prostate and adrenal nodules: diagnosis from pathology and mNGS, a case report.

Disseminated Cryptococcosis infection typically occurs in immunocompromised patients, often manifested as pneumonia or meningoencephalitis. Cases with involvement of either prostate or adrenal glands are less frequent. We describe a case of an immunocompromised 62-year-old man with new-found Idiopathic CD4 + T lymphocytopenia who presented with urinary irritation symptoms followed by headache. The patient was finally diagnosed as disseminated cryptococcosis of prostate, adrenal gland involvement with the help of combining histopathology of formalin-fixed, paraffin-embedded tissue with metagenomic next-generation sequencing technique to identify C neoformans sensu stricto in prostate, adrenal gland tissues. Clinicians should be aware of atypical presentations of cryptococcal disease. In this case of cryptococcosis in immunocompromised patients, we find that cryptococcosis can affect varied organs simultaneously and should be considered in the differential of infectious diseases. And mNGS technology helps to confirm the diagnosis.

An early clinical phenotype of necrotizing meningoencephalitis in the Pug reveals similarities to multiple sclerosis in humans.

Necrotizing meningoencephalitis (NME) is a fatal neuroinflammatory disease that previously carried a uniformly grave prognosis. Our recent identification of a novel early form of NME in Pugs suggests that disease onset and progression are likely more insidious than previously recognized and provides new hope that early therapeutic intervention may halt disease progression and ultimately prevent or cure NME. This novel perspective also sheds new light on the clinical similarities to multiple sclerosis (MS) in humans and provides a rationale for cross-species translation. The history of recent scientific discoveries in NME and new parallels between MS and NME will be reviewed.

A case of meningoencephalitis caused by multisystem inflammatory syndrome in adult SARS-CoV-2 infection.

A 37-year-old woman was hospitalized with fever and consciousness disturbance. She showed systemic inflammation with stress cardiomyopathy. Brain computed tomography showed diffuse brain edema. Cerebrospinal fluid (CSF) findings revealed markedly elevated cerebrospinal fluid pressure with pleocytosis, elevated protein, and elevated interleukin 6. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nicking enzyme amplification reaction test using a nasopharyngeal swab was positive, and the patient was diagnosed with SARS-CoV-2 infection. From the negative result of the CSF SARS-CoV-2 polymerase chain reaction test and no findings of bacterial or viral infection, we diagnosed meningoencephalitis by multisystem inflammation syndrome in adults (MIS-A). Intravenous methylprednisolone pulse therapy improved her symptoms and brain edema. There have been no cases of MIS-A with meningoencephalitis, and no initial treatment strategy has been established, especially in emergency cases of suspected MIS-A. The present case suggested Early intravenous methylprednisolone pulse with anti-coronaviral therapies after the exclusion of bacterial infection would be useful in suspected MIS-A with emergent meningoencephalitis cases.

Powassan Virus Encephalitis: A Tertiary Center Experience.

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.