Persistent marked cerebrospinal fluid eosinophilia in a dog with primary central nervous system histiocytic sarcoma.

A 6-year-old female spayed Jack Russell Terrier was evaluated for episodic seizure-like activity and intermittent obtundation over the previous 3 weeks. Magnetic resonance imaging (MRI) of the brain revealed mild generalized dilation of the ventricular system with periventricular edema. A focal area of mildly increased lepto- and pachymeningeal contrast uptake in the region of the right parietal and occipital lobes was observed. Analysis of cerebrospinal fluid (CSF) revealed marked mixed pleocytosis with 20% eosinophils and no atypical cells or microorganisms. The dog transiently improved with prednisolone for suspected eosinophilic meningoencephalitis/meningoencephalomyelitis of unknown origin (MUO) but worsened over the following 5 months. Brain MRI and CSF sampling were repeated. Additional multifocal lesions were evident in the brainstem and cerebellum. On CSF analysis, the eosinophilic pleocytosis and increased total protein persisted. The clinical signs progressed despite treatment, and the patient was euthanized 6 weeks later. A post-mortem examination was performed. Histopathology and immunohistochemistry revealed a multifocal neoplastic proliferation of cells in the brain, diffusely and strongly positive for ionized calcium-binding adapter molecule (Iba-1) and negative for AE1/AE3 pan-cytokeratin and glial-fibrillar-acid-protein (GFAP) immunostaining, consistent with a diagnosis of histiocytic sarcoma (HS). No other organic lesions were found; therefore, the neoplasm was considered a primary HS of the central nervous system (CNS). This case report stresses the importance of considering primary CNS HS in the differential diagnosis of dogs with marked CSF eosinophilia, even in the absence of atypical cells on cytologic examination.

SCHISTOSOMAL MYELORADICULOPATHY IN A NON-ENDEMIC AREA.

OBJECTIVE: To report a schistosomal myeloradiculopathy case in a non-endemic area. CASE DESCRIPTION: A previously healthy 11-year-old boy, stricken by an acute loss of strength on his lower limbs, followed by a loss of strength on his upper limbs and upper body, associated with altered sensitivity of the vesical globe formation. The patient's cerebrospinal fluid analysis showed eosinophilic meningitis, in addition to peripheral eosinophilia. The investigation resulted in a positive serology for Schistosoma mansoni. The treatment included steroids and praziquantel 60mg/kg, with a new dose after a month, as well as physical therapy for rehabilitation. The patient evolved with clinical improvement in the neurological exam, with a medullary section initially at C6, but now at T6. The patient is kept at prednisolone use (30mg/day) and longterm urinary catheter dependence. COMMENTS: The schistosomiasis is endemic in many regions of Brazil; however, it has low incidence in the south of the country. Among its main manifestations, the schistosomal myeloradiculopathy is the most severe ectopic form of the disease, and should be suspected in patients with low back pain, strength and/or sensibility disorder of the lower limbs or urinary tract's disturbance. Early diagnosis and treatment should be done in order to reduce severe neurological sequelae. Treatment includes schistosomiasis drugs, corticosteroids and/or surgery.

Schistosomal myeloradiculopathy in a non-endemic area / Mielorradiculopatia esquistossomótica em região não endêmica

ABSTRACT Objective: To report a schistosomal myeloradiculopathy case in a non-endemic area. Case description: A previously healthy 11-year-old boy, stricken by an acute loss of strength on his lower limbs, followed by a loss of strength on his upper limbs and upper body, associated with altered sensitivity of the vesical globe formation. The patient's cerebrospinal fluid analysis showed eosinophilic meningitis, in addition to peripheral eosinophilia. The investigation resulted in a positive serology for Schistosoma mansoni. The treatment included steroids and praziquantel 60mg/kg, with a new dose after a month, as well as physical therapy for rehabilitation. The patient evolved with clinical improvement in the neurological exam, with a medullary section initially at C6, but now at T6. The patient is kept at prednisolone use (30mg/day) and longterm urinary catheter dependence. Comments: The schistosomiasis is endemic in many regions of Brazil; however, it has low incidence in the south of the country. Among its main manifestations, the schistosomal myeloradiculopathy is the most severe ectopic form of the disease, and should be suspected in patients with low back pain, strength and/or sensibility disorder of the lower limbs or urinary tract's disturbance. Early diagnosis and treatment should be done in order to reduce severe neurological sequelae. Treatment includes schistosomiasis drugs, corticosteroids and/or surgery.

RESUMO Objetivo: Relatar um caso de mielorradiculopatia esquistossomótica em área não endêmica. Descrição do caso: Paciente do sexo masculino, 11 anos, previamente hígido, com história aguda de paresia de membros inferiores, que evoluiu para membros superiores e tronco, associada à alteração de sensibilidade e formação de globo vesical. O exame do líquor demonstrava meningite eosinofílica, além de eosinofilia periférica. A investigação resultou em sorologia positiva para Schistosoma mansoni. O tratamento foi realizado com corticoterapia e praziquantel 60 mg/kg, com nova dose após um mês, além de fisioterapia para reabilitação. Evoluiu com melhora clínica no exame neurológico, com nível de secção medular que inicialmente correspondia a C6, encontrando-se atualmente em T6. Mantém uso de prednisolona 30 mg/dia e dependência de sonda vesical de demora. Comentários: A esquistossomose é uma doença endêmica em muitas regiões do Brasil, porém com pouca incidência no Sul do país. Dentre as principais manifestações, a mielorradiculopatia esquistossomótica é a forma ectópica mais grave e deve ser suspeitada na vigência de dor lombar, alteração de força e/ ou sensibilidade de membros inferiores e distúrbio urinário. O diagnóstico e o tratamento devem ser instituídos precocemente para diminuir o risco de sequelas neurológicas graves. O tratamento pode ser realizado com esquistossomicidas, corticosteroides e/ ou cirurgia.

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.

Clinical presentation and magnetic resonance imaging findings in 11 dogs with eosinophilic meningoencephalitis of unknown aetiology.

OBJECTIVES: To describe the clinical presentation, MRI findings and outcome in dogs with eosinophilic meningoencephalitis of unknown origin. MATERIALS AND METHODS: Dogs were included in this retrospective study if they had complete medical records, complete neurological examination, MR imaging, cerebellomedullary cerebrospinal fluid sample consistent with eosinophilic pleocytosis and negative infectious disease testing. RESULTS: Eleven dogs were included with a median age of 22·0 months (range 7·6 to 92·0 months). Nine breeds were represented. Neurological abnormalities included obtundation (n=10), menace response deficits (n=9), proprioceptive deficits (n=7), ataxia (n=7) and seizures (n=2). Neuroanatomical localisation was multi-focal (n=4), central vestibular system (n=4), diffuse forebrain (n=2) or left trigeminal/facial nerves (n=1). Seven dogs had peripheral eosinophilia. Ten dogs had bilateral symmetrical lesions affecting the cortical grey matter, which was hyperintense on T2-weighted and fluid-attenuating inversion recovery images and iso- to hypointense on T1-weighted images with associated meningeal contrast enhancement. MRI findings were consistent with diffuse meningitis and atrophy or necrosis of cortical grey matter. One dog had increased contrast uptake in the left trigeminal nerve. Ten dogs receiving corticosteroids survived to discharge, with seven also receiving cytarabine arabinoside. Median survival time was 762 days. CLINICAL SIGNIFICANCE: Eosinophilic meningoencephalitis of unknown origin affects younger larger-breed dogs, with the majority having suspected diffuse cerebrocortical meningitis and cortical (polio)encephalitis, which can be identified on MRI. Response to immunosuppressive treatment is good in the medium to long term, although further studies are required in this area.

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.

Thoracic Myelopathy Due to Gnathostomiasis Acquired in New Zealand.

Gnathostomiasis is a zoonotic disease endemic in Asia. It most commonly manifests as gastrointestinal and cutaneous disease. Central nervous system involvement is a rare but feared complication, often leaving patients with permanent neurologic deficits. Clinicians outside of Asia and Latin America may have little experience with this illness, causing delays in diagnosis and treatment. We describe a 40-year-old woman who developed a progressive myelopathy over 18 months. She had never traveled outside of New Zealand. Cerebrospinal fluid (CSF) showed marked eosinophilia and Gnathostoma serology was positive in both serum and CSF. This is the first report of gnathostomiasis acquired in New Zealand, and the first case of neurognathostomiasis reported outside Asia. Clinicians should include neurognathostomiasis in the differential diagnosis of myelopathy and CSF eosinophilia, even if there is no history of travel to endemic areas.

EGYPTIAN EOSINOPHILIC AND INFECTIOUS MENINGOENCEPHA- LITIS AND THEIR IMPACT ON PSYCHOLOGICAL ASPECTS.

Meningoencephalitis is an acute inflammation of the brain and spinal cord & their covering protective membranes. Meningitis can be life-threatening because of the inflammation's proximity to the brain and spinal cord; therefore, the condition is classified as a medical emergency. The commonest symptoms of meningitis are headache and neck stiffness associated with fever, confusion or altered consciousness, vomiting, and an inability to tolerate light (photophobia) or loud noises (phonophobia). Children often exhibit only nonspecific symptoms, such as irritability and drowsiness. If a rash is present, it may indicate a particular cause of meningitis; for instance, meningitis caused by meningococcal bacteria may be accompanied by a characteristic rash. A broad variety of allergic, infectious, neoplastic, and idiopathic diseases are associated with increased blood and/or tissue eosinophilia and range in severity from self-limited conditions to life-threatening disorders. Although accepted upper limits of normal blood eosinophil numbers vary somewhat, a value above 600 eosinophils /microL of blood is abnormal in the vast majority of cases. Generally speaking, there are several possible causes of eosinophils in the CSF; undoubtedly parasitic infection is one of the main causes.

Cryptococcal eosinophilic meningitis in a patient with sarcoidosis.

A 51-year-old African-American man with underlying pulmonary, hepatic and splenic sarcoidosis, reported a 3-day history of headache, neck stiffness and photophobia. He was not using medication for chronic sarcoidosis. Physical examination was significant for nuchal rigidity. Lumbar puncture revealed marked eosinophilia in the cerebrospinal fluid, which, on further analysis, demonstrated a positive cryptococcal antigen. HIV antibody and PCR tests were negative. Bronchoscopy and fungal blood cultures were also negative. The patient was started on amphotericin B and flucytosine, with significant clinical improvement. He recovered well without any neurological sequelae and remained symptom-free at 2-week follow-up. Cryptococcal central nervous infections are uniformly fatal if left untreated. Prompt diagnosis and treatment is essential, to prevent the associated high morbidity and mortality.

Cerebrospinal fluid eosinophilia in a child with neuroborreliosis.

Cerebrospinal fluid eosinophilia is rare and usually associated with eosinophilic meningitis caused by helminthic infections. It is also observed in bacterial or fungal meningitis (syphilis, tuberculosis, coccidioidomycosis), in patients with malignancies, ventriculoperitonial shunts, hypereosinophilic syndrome or allergy to some medications. Here we present a case of an 8-year-old boy admitted with fever and clinical signs of meningitis. Cerebrospinal fluid (CSF) analysis showed marked eosinophilia. Basing on further serological CSF testing the diagnosis of borreliosis was established. Cerebrospinal fluid eosinophilia in Borrelia burgdorferi infection has never been reported before.

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.

Meningitis tras anestesia y analgesia espinal / No disponible

El objetivo de esta revisión es una puesta al día en la etiología, diagnóstico, profilaxis y tratamiento de la meningitis tras anestesia y analgesia espinales. Aunque es una complicación mayor de esta técnica y su incidencia es baja, cada vez son más frecuentes los casos publicados en la literatura médica. Según su etiología se les clasifica en meningitis sépticas, víricas y asépticas. Las meningitis sépticas son las más frecuentes, y en su etiología cada vez juega un papel más destacado como agente implicado el estreptococo salivarius. Como meningitis asépticas se clasifican aquellas en las que el cultivo de líquido cefalorraquídeo es negativo, con un periodo de latencia de síntomas inferior a seis horas, que pueden cursar con eosinofilia en el líquido cefalorraquídeo y unos niveles cercanos a la normalidad en la glucorraquia. Suelen tener buena respuesta y evolución con tratamiento antibiótico con vancomicina y cefalosporinas de tercera generación. Como profilaxis incidir en las medidas de asepsia, sobre todo en el uso de mascarilla facial para realizar la técnica, como práctica para disminuir la incidencia de gérmenes cuyo origen está en la cavidad oral y orofaringe. Asimismo podrían reducir la incidencia de meningitis las medidas de asepsia tales como el lavado de manos, uso de guantes y asepsia de la piel. La diferenciación entre meningitis séptica y aséptica se hará con mayor seguridad cuando se estandaricen las técnicas para detectar genoma bacteriano en el líquido cefalorraquídeo; actualmente se etiquetan como meningitis asépticas aquellas en las que el cultivo de líquido cefalorraquídeo es negativo y cuya tinción de Gram es negativa. Pese a que el pronóstico y evolución en rasgos generales de las meningitis tras anestesia y analgesia espinal es bueno, en comparación con las meningitis adquiridas en la comunidad, por la escasa virulencia de las bacterias implicadas (Estreptococo salivarius), hay descritos casos con mala evolución de meningoencefalitis supurativa que han llevado a la muerte en pocas horas (AU)

The objective of this review is an update on etiology, diagnosis, prevention and treatment of meningitis after spinal anesthesia and analgesia. Although it is a major complication of this technique and its incidence is low, there are more and more frequent cases in the medical literature. According to its etiology are classified in septic meningitis, viral and aseptic. The septic meningitis are the most common, and its etiology increasingly plays a more prominent role as Streptococcus salivarius agent involved. Aseptic meningitis are classified as those in which cerebrospinal fluid culture is negative, with a latency period of symptoms less than six hours, which may present with eosinophilia in the cerebrospinal fluid and levels close to normal in the CSF glucose. They usually have good response and evolution with antibiotic treatment with vancomycin and third-generation cephalosporins. Prophylaxis influence the aseptic precautions, especially the use of a face mask to perform the technique, as practical to reduce the incidence of bacteria whose origin is in the oral cavity and oropharynx. They could also reduce the incidence of aseptic meningitis measures such as hand washing, use of gloves and skin antisepsis. The differentiation between aseptic meningitis and septic will more securely when standardize techniques for detecting bacterial genome in the cerebrospinal fluid, now labeled as aseptic meningitis those in which cerebrospinal fluid culture is negative and whose negative Gram stain . Although the prognosis and evolution in general features of meningitis after spinal anesthesia and analgesia is good, compared with community-acquired meningitis, the low virulence of the bacteria involved (Streptococcus salivarius), cases have been described with poor outcome suppurative meningoencephalitis have led to death within hours (AU)

Eosinophilic meningitis caused by primary angiitis of the central nervous system.

Eosinophilic meningitis is defined as the presence of 10 eosinophils/mm(3) in the cerebrospinal fluid (CSF) or eosinophils accounting for more than 10% of CSF leukocytes. A 76-year-old man who developed cognitive dysfunction and consciousness disturbance had eosinophilic meningitis (his CSF contained 19.0% eosinophils). Because the etiology was unknown, we performed a brain biopsy. The pathological findings showed inflammatory infiltration in the small-sized arteries of the meninges. The patient was ultimately diagnosed as having primary angiitis of the central nervous system (PACNS). Eosinophilic meningitis occurring in a patient with PACNS is extremely rare, and this is the first report of this condition in Japan.

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.

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 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.