A Rare Etiology for Ascending Paralysis in an Infant.

An 11-month-old male infant with ascending paralysis had an unremarkable initial cerebrospinal fluid (CSF) analysis and imaging. Progressive neurological symptoms resulted in repeated CSF sampling, microscopy, and plasma microbial cell-free DNA next-generation sequencing analysis, that in combination with epidemiology, confirmed the diagnosis.

Angiostrongylosis meningomyelitis without blood eosinophilia.

Angiostrongylus cantonensis and Gnathostoma spinigerum usually cause eosinophilic meningitis with associated peripheral blood eosinophilia. A 44-year-old man developed acute paraplegia with bowel and bladder dysfunction. Spinal magnetic resonance images showed a long T2W hyperintensity signal from the 1st to 8th spinal thoracic level. Cerebrospinal fluid analysis revealed eosinophilia and elevated cerebrospinal fluid protein, whereas differential leucocytes count in peripheral blood was unremarkable. Positive immunoblot tests for A. cantonensis antibody in serum and cerebrospinal fluid were reported. The patient had neither history of recent traveling to the high endemic areas of the parasite in Thailand, nor consumption the parasitic hosts. Immediate treatment with intravenous pulse methylprednisolone and oral albendazole resulted in complete recovery. Despite an unremarkable differential leucocytes count, absence a history of parasitic hosts consumption, and a less common presentation with meningomyelitis, A. cantonensis should be considered when cerebrospinal fluid eosinophilia presents.

Angiostrongyliasis detected by next-generation sequencing in a ELISA-negative eosinophilic meningitis: A case report.

Next-generation sequencing (NGS) is an emerging method with the potential of pan-pathogen screening. This study described a case of eosinophilic meningitis (EoM) with enzyme-linked immunosorbent assay (ELISA)-negative results for Angiostrongylus cantonensis (A. cantonensis), Trichinella spiralis and Paragonimus westermani and a positive identification of A. cantonensis by NGS in the cerebrospinal fluid.

Magnetic resonance imaging findings and clinical manifestations in cerebral angiostrongyliasis from Dali, China.

PURPOSE: To analyze magnetic resonance imaging (MRI) findings and clinical diagnosis and treatment data relating to Angiostrongylus cantonensis infection to gain insight into the disease. MATERIALS AND METHODS: We retrospectively analyzed the epidemiology, clinical manifestations, diagnosis and treatment data, imaging manifestations, and outcomes of 27 patients who were clinically diagnosed with angiostrongyliasis and who underwent contrast-enhanced brain MRI. RESULTS: Patients with A. cantonensis infection had a history of eating raw mollusks in the endemic area, and they mainly presented with dizziness and headache of varying degrees and vomiting (n = 7). Laboratory examinations revealed increased peripheral blood and cerebrospinal fluid (CSF) eosinophils, as well as increased CSF protein levels. Brain MRI findings mainly included eosinophilic meningitis, whereas linear or nodular enhancement of the pia mater was observed in enhanced T1-weighted and fluid-attenuated inversion recovery images, accompanied by encephalitis or vasculitis. Meningitis manifested as multiple, thickened flow voids around the meninges, and contrast-enhanced scans showed substantial enhancement in intracranial dilated and hyperplastic blood vessels. CONCLUSION: The possibility of A. cantonensis infection should be considered in the effective use of albendazole or mebendazole as a treatment. Combining clinical history with laboratory examination is helpful in diagnosing A. cantonensis infection. A final definite diagnosis can be confirmed by detecting larvae in the CSF. The administration of corticosteroids during pathogen therapy can substantially reduce the therapeutic response.

Dexamethasone Downregulates Expressions of 14-3-3ß and γ-Isoforms in Mice with Eosinophilic Meningitis Caused by Angiostrongylus cantonensis Infection.

Steroids are commonly used in patients with eosinophilic meningitis caused by A. cantonensis infections. The mechanism steroids act on eosinophilic meningitis remains unclear. In this mouse experiments, expressions of 14-3-3 isoform ß and γ proteins significantly increased in the CSF 2-3 weeks after the infection, but not increasedin the dexamethasone-treated group. Expression of 14-3-3 ß, γ, ε, and θ isoforms increased in brain meninges over the 3-week period after infection and decreased due to dexamethasone treatment. In conclusion, administration of dexamethasone in mice with eosinophilic meningitis decreased expressions of 14-3-3 isoform proteins in the CSF and in brain meninges.

Eosinophilic cerebrospinal fluid pleocytosis associated with neural Angiostrongylus vasorum infection in a dog.

A 1-year-old, female intact Pug dog was presented to the Small Animal Teaching Hospital of the University of Liverpool with a 4-week history of progressive multifocal intracranial signs. Magnetic resonance imaging (MRI) detected multiple hemorrhagic lesions in the brain. The Baermann and zinc sulfate flotation tests with centrifugation, performed on fecal samples, were positive for lungworm larvae and an antigenic test confirmed Angiostrongylus vasorum infection. Anthelmintic treatment was started with a consequent marked clinical improvement. Seventy days later, the dog was clinically normal, and no larvae were detected on the Baermann test. Repeat MRI of the brain revealed marked improvement of the hemorrhagic lesions. Cerebrospinal fluid analysis (CSF) showed marked eosinophilic pleocytosis, and anthelmintic treatment was restarted. A follow-up CSF analysis 4 months after the first presentation revealed resolution of the eosinophilic pleocytosis. This is the first case report of marked eosinophilic pleocytosis associated with neural A vasorum infection in a dog. The CSF eosinophilic pleocytosis persisted for several weeks after treatment, even in the absence of concurrent clinical signs and with a negative A vasorum Baermann test.

Angiostrongylus cantonensis DNA in Cerebrospinal Fluid of Persons with Eosinophilic Meningitis, Laos.

Definitive identification of Angiostrongylus cantonensis parasites from clinical specimens is difficult. As a result, regional epidemiology and burden are poorly characterized. To ascertain presence of this parasite in patients in Laos with eosinophilic meningitis, we performed quantitative PCRs on 36 cerebrospinal fluid samples; 4 positive samples confirmed the parasite's presence.

Angiostrongylus cantonensis Meningitis and Myelitis, Texas, USA.

Infection with Angiostrongylus cantonensis roundworms is endemic in Southeast Asia and the Pacific Basin. A. cantonensis meningitis and myelitis occurred in summer 2013 in a child with no history of travel outside of Texas, USA. Angiostrongyliasis is an emerging neurotropic helminthic disease in Texas and warrants increased awareness among healthcare providers.

Anti-N-methyl-D-aspartate receptor encephalitis associated with intracranial Angiostrongylus cantonensis infection: a case report.

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a recently described paraneoplastic syndrome with prominent neuropsychiatric symptoms. Many of these cases are associated with neoplasma especially teratoma. In addition, a few of cases with anti-NMDAR antibodies triggered by viral infection have been reported, but never by parasitic infection. Here, we report a novel case of NMDA receptor encephalitis in a 51-year-old male related to the development of anti-NMDAR antibodies triggered by Angiostrongylus cantonensis infection.

Fibronectin changes in eosinophilic meningitis with blood-CSF barrier disruption.

Fibronectin, which is present at relatively low levels in healthy central nervous systems (CNS), shows increased levels in meningitis. In this study, fibronectin processing was correlated with the increased permeability of the blood-cerebrospinal fluid (CSF) barrier as well as with the formation of eosinophil infiltrates in angiostrongyliasis meningitis. The immunohistochemistry results show matrix metalloproteinase-9 (MMP-9) is localized in the choroid plexus epithelium. Coimmunoprecipitation demonstrated fibronectin strongly binds MMP-9. Furthermore, treatment with the MMP-9 inhibitor GM6001 significantly inhibited fibronectin processing, reduced the blood-CSF barrier permeability, and decreased the eosinophil counts. The decreased fibronectin processing in CSF implies decreased cellular invasion of the subarachnoid space across the blood-CSF barrier. Therefore, increased fibronectin processing may be associated with barrier disruption and participate in the extravasation and migration of eosinophils into the CNS during experimental parasitic infection.

14-3-3ß protein expression in eosinophilic meningitis caused by Angiostrongylus cantonensis infection.

BACKGROUND: Angiostrongylus cantonensis is a parasite endemic in the Southeast Asian and Pacific regions. Humans are incidentally infected either by eating uncooked intermediate hosts or by consuming vegetables containing the living third-stage larvae. The 14-3-3ß protein is a cerebrospinal fluid (CSF) marker of neuronal damage during the development of Creutzfeldt-Jakob disease. In addition, increased 14-3-3ß protein is also found in CSF from patients with a variety of neurological disorders. The goal of this study is to determine the roles of serum/CSF14-3-3ß protein in patients with eosinophilic meningitis. METHODS: In a cohort study among nine Thai laborers with eosinophilic meningitis due to eating raw snails (Pomacea canaliculata), we examined the CSF weekly while patients were still hospitalized and followed up the serum for 6 months. The levels of 14-3-3ß protein in CSF were analyzed by western blot and an in-house 14-3-3ß enzyme-linked immunosorbent assay (ELISA) measurement was established and tested in an animal model of eosinophilic meningitis. RESULTS: The elevated 14-3-3ß level was detected in the CSF from eight out of nine (81%) patients After 2 weeks of treatment, all patients showed a declined level or cleared of 14-3-3ß protein in the CSF. By developing an in-house ELISA for measurement of 14-3-3ß protein, it was found that the serum 14-3-3ß level was significantly increased in patients during initial visit. . This finding was consistent to the animal experiment result in which there was severe blood brain barrier damage three weeks after infection and increased 14-3-3ß protein expression in the CSF and serum by western blot and in house ELISA. After treatment, the serum 14-3-3ß level in meningitis patients was rapidly returned to normal threshold. There was a correlation between initial CSF 14-3-3ß level with severity of headache (r = 0.692, p = 0.039), CSF pleocytosis (r = 0.807, p = 0.009) and eosinophilia (r = 0.798, p = 0.01) in the CSF of patients with eosinophilic meningitis (Spearman's correlation test). CONCLUSIONS: The serum 14-3-3ß concentrations may constitute a useful marker for blood brain barrier damage severity and follow up in patients with eosinophilic meningitis caused by A. cantonensis.

Intrathecal activation as a typical immune response within the central nervous system in angiostrongyliasis.

Angiostrongylus cantonensis is a zoonotic pathogen that occasionally causes human angiostrongyliasis; its main clinical manifestation is eosinophilic meningitis. This report defines the concept of intrathecal activation of complement as evidence of intrathecal synthesis of major immunoglobulins during this disease. Details are presented of the activation of complement system components in cerebrospinal fluid, and their application to our understanding of this tropical disease, which is emerging in the Western hemisphere. Intrathecal synthesis of at least one of the major immunoglobulins and a wide spectrum of patterns may be observed. Although intrathecal synthesis of C3c is always present, C4 intrathecal synthesis does not occur in every patient. The diversity of intrathecal synthesis and activation of the different complement pathways enables their division into three variant groups (A, B, and C). Variant group A includes the classical and/or lectin pathway and involves two or more major immunoglobulins with C3 and C4 intrathecal synthesis. Variant group B involves C4 in cerebrospinal fluid that comes from blood in the intrathecal activation of the classical pathway. Variant group C includes the alternative pathway.

Molecular diagnosis of eosinophilic meningitis due to Angiostrongylus cantonensis (Nematoda: Metastrongyloidea) by polymerase chain reaction-DNA sequencing of cerebrospinal fluids of patients.

Cerebrospinal fluid (CSF) samples from clinically diagnosed patients with detectable Angiostrongylus cantonensis-specific antibodies (n = 10), patients with clinically suspected cases that tested negative for A. cantonensis-antibodies (n = 5) and patients with cerebral gnathostomiasis (n = 2) and neurocysticercosis (n = 2) were examined by a single-step polymerase chain reaction (PCR) method using the AC primers for the 66-kDa native protein gene. The PCR method detected A. cantonensis DNA in CSF samples from four of 10 serologically confirmed angiostrongyliasis cases. The PCR results were negative for the remaining CSF samples. The nucleotide sequences of three positive CSF-PCR samples shared 98.8-99.2% similarity with the reference sequence of A. cantonensis. These results indicate the potential application of this PCR assay with clinical CSF samples for additional support in the confirmation of eosinophilic meningitis due to A. cantonensis.

Molecular diagnosis of eosinophilic meningitis due to Angiostrongylus cantonensis (Nematoda: Metastrongyloidea) by polymerase chain reaction-DNA sequencing of cerebrospinal fluids of patients

Cerebrospinal fluid (CSF) samples from clinically diagnosed patients with detectable Angiostrongylus canto-nensis-specific antibodies (n = 10), patients with clinically suspected cases that tested negative for A. cantonensis-an-tibodies (n = 5) and patients with cerebral gnathostomiasis (n = 2) and neurocysticercosis (n = 2) were examined by a single-step polymerase chain reaction (PCR) method using the AC primers for the 66-kDa native protein gene. The PCR method detected A. cantonensis DNA in CSF samples from four of 10 serologically confirmed angiostrongyliasis cases. The PCR results were negative for the remaining CSF samples. The nucleotide sequences of three positive CSF-PCR samples shared 98.8-99.2% similarity with the reference sequence of A. cantonensis. These results indicate the potential application of this PCR assay with clinical CSF samples for additional support in the confirmation of eosinophilic meningitis due to A. cantonensis.

Cerebrospinal fluid eosinophilia is a sensitive and specific test for the diagnosis of Parelaphostrongylus tenuis in camelids in the northeastern United States.

Aberrant migration of Parelaphostrongylus tenuis in camelids results in neurologic deficits, recumbency, and sometimes death. An antemortem diagnosis of P. tenuis in camelids is typically based upon the presence of characteristic asymmetric neurologic deficits, known exposure to white-tailed deer, cerebrospinal fluid (CSF) eosinophilia, and response to treatment. The diagnostic accuracy of CSF eosinophil percentage for the diagnosis of P. tenuis in camelids has not been critically examined. The objective of the current study was to determine the sensitivity (Se) and specificity (Sp) of CSF eosinophil percentage, CSF eosinophil concentration, total nucleated cell concentration, and protein concentration for the antemortem diagnosis of P. tenuis. Medical records of camelids admitted to Cornell University with clinical signs of neurologic disease, CSF analysis, and necropsy were examined from January 2000 through December 2009. Se and Sp were determined by receiver operating characteristic curves in camelids diagnosed with P. tenuis (n = 13) or other conditions (n = 24) based on postmortem examination. More than 17% of eosinophils in CSF had a Se of 85% and Sp of 92% for P. tenuis diagnosis (area under the curve [AUC]: 0.87; SE AUC: 0.07; P < 0.0001; 95% confidence interval [CI] AUC: 0.72-0.96), and >1.4 eosinophils/µl of CSF had a Se of 85% and Sp of 96% (AUC: 0.9; SE AUC: 0.06; P < 0.0001; 95% CI AUC: 0.76-0.97). Cerebrospinal fluid eosinophil percentage and concentration are sensitive and specific methods for diagnosing P. tenuis antemortem in camelids residing in regions endemic to white-tailed deer.

How can clinicians ensure the diagnosis of meningitic angiostrongyliasis?

Meningitic angiostrongyliasis (MA), caused by Angiostrongylus cantonensis, is often diagnosed by clinical criteria alone, because the confirmative serologic tests are not always available in the rural endemic areas. In this study, we evaluated the relationship between various clinical parameters of MA and the sero-positivity to sort out the predictive parameters to ensure the diagnosis. We enrolled consecutive adults in whom MA had been clinically diagnosed, who had serologic results for A. cantonensis, and negative serologic results for Gnathostoma spinigerum. There were 75 eligible patients; 26 (34.7%) and 49 (65.3%) patients who had negative and positive serologic tests for A. cantonensis, respectively. Baseline characteristics and laboratory results were comparable between sero-positive and -negative groups. Only the cerebrospinal fluid (CSF) eosinophil counts of 40% or higher was significantly predictive for positive serologic test with the adjusted odds ratio of 4.970 (95% confidence interval of 1.337-18.477). In diagnostic facilities in the endemic areas with the limited availability of serologic tests, clinicians can ensure the diagnosis of MA by using CSF eosinophil level.