Differential diagnosis of eosinophilic meningitis

Meningitis - infection o f the meninges - can be attributed to a variety o f agents, including bacteria, protozoa and some helminths. In helminth infections, but rarely in protozoal infections, eosinophilia is a common sign. Thus eosinophilic meningitis (EOM) is typically associated with certain helminth infections in which nervous system involvement occurs. Among the most important of these are ongiostrongyliosis, gnathostomiasis, porogonimiasis and cysticercosis (see Fig. 1). Here, Nibha Jaroonvesoma discusses the key distinctions between such infections.     

The discovery of Angiostrongylus cantonensis as a cause of human eosinophilic meningitis

The theoretical and subsequent confirmation in 1961 of the rat lungworm, Angiostrongylus cantonensis, as the causative agent o f eosinophilic meningitis is one o f the remarkable parasitological findings of the twentieth century. Here, Joseph Alicato briefly summarizes the early history and his epidemiological studies on the relationship between the parasite and the epidemics o f encephalitis that swept through Oceania after the Second World War.     

Specificity of immunoblotting analyses in eosinophilic meningitis

Angiostrongylus cantonensis and Gnathostoma spinigerum are the two most common causative parasites of eosinophilic meningitis (EOM). Serological tests are helpful tools for confirming the identity of the pathogen. Recent reports determined the specificity of such tests by using normal healthy controls. There have been limited studies done to rule out the cross-reactivity between these two causative parasites of EOM. This study aims to assess the specificity of the serological test in EOM by using each condition as a control for the other. Thirty-three patients with a diagnosis of EOM were enrolled. Sera from 22 patients with a positive 29-kDa antigenic diagnostic band of A. cantonensis were tested for the 21 and 24-kDa antigenic bands of G. spinigerum. Similarly, sera of 11 gnathostomiasis patients were tested for the 29-kDa diagnostic band for A. cantonensis. Only one patient in the angiostrongyliasis group had a positive result for the 21 and 24-kDa antigenic bands of G. spinigerum, while no gnathostomiasis patients showed a positive result for the 29-kDa antigenic band of A. cantonensis. The specificity of the 21 and 24-kDa antigenic bands for gnathostomiasis and the 29-kDa antigenic band for A. cantonensis was 95.5% and 100%, respectively. The antigenic bands for the diagnosis of gnathostomiasis and angiostrongyliasis in EOM were highly specific.     

Efficacy of curcumin therapy against Angiostrongylus cantonensis-induced eosinophilic meningitis

Angiostrongylus cantonensis can invade the central nervous system, leading to human eosinophilic meningitis or eosinophilic meningoencephalitis. Curcumin is a natural product which has the effects of anti-inflammation, anti-oxidation and anti-carcinogensis, while the administration of curcumin has been reported to possibly relieve the symptoms of meningitis. The present study tested the potential efficacy of curcumin in A. cantonensis-induced eosinophilic meningitis of BALB/c mice. Assay indicators for the therapeutic effect included the larvicidal effect, eosinophil counts and matrix metalloproteinase-9 (MMP-9) activity in angiostrongyliasis. Eosinophils were mildly reduced in treatment groups compared with infected-untreated mice. However, there were no significant differences in larvicidal effects or MMP-9 activity. This study suggests that anti-inflammatory treatment with curcumin alone has low efficacy, but the treatment does not interfere with MMP-9 expression and is not useful for larvicidal effects. The possible reasons include low curcumin across the blood-brain barrier and also those larvae that survive stimulate MMP-9 production, which promotes blood-brain barrier damage, with leukocytes then crossing the blood-brain barrier to cause meningitis. Further studies will be required to test these possibilities.     

Bronchioloalveolar carcinoma presenting with meningeal carcinomatosis. Cytologic diagnosis in cerebrospinal fluid

The cytologic findings in a 35-year-old patient with bronchioloalveolar carcinoma who initially presented with central nervous system involvement are reported. Following the cytologic diagnosis of carcinomatous meningitis (metastatic adenocarcinoma), an open lung biopsy was performed, which confirmed the presence of a primary pulmonary neoplasm (bronchioloalveolar carcinoma). This case illustrates the importance of the cytologic diagnosis of a clinically unsuspected primary neoplasm. Further, together with three earlier reported cases, it indicates that, in young patients, tumor cells shedding into the cerebrospinal fluid can be the first indication of bronchioloalveolar carcinoma.     

Multi-immunodot for rapid differential diagnosis of eosinophilic meningitis due to parasitic infections

A multi-dot enzyme-linked immunosorbent assay (ELISA) was developed for the rapid and simple differential diagnosis of eosinophilic meningitis due to helminth infections. Ultrafiltered, purified antigens of Parastrongylus (=Angiostrongylus) cantonensis, Gnathostoma spinigerum and Taenia solium metacestodes, the most common parasites that invade the central nervous system and cause eosinophilic pleocytosis, were dotted onto a single nitrocellulose membrane strip. Antigen-coated strips, when blocked with 5% skimmed milk and dried, were stable for at least 6 months at 4 degrees C. With peroxidase conjugated anti-human immunoglobulins and 4-chloro-1-naphthol as a substrate, antibodies in the corresponding patients' sera were clearly detected on the membrane strip as well-defined blue dots. Although cross-reactions between P. cantonensis and G. spinigerum antigens were observed with the use of partially purified antigens, the darkest dot correlated well with the infecting parasites in all cases. This fast, easy and economical multiple dot-blot ELISA method is useful for the differential diagnosis of eosinophilic meningitis caused by parasitic helminths, as semi-purified antigens can be easily obtained by ultrafiltration and used. Further improvements using highly specific parasite antigens may make this multi-immunodot test more suitable for wide-scale use in field studies and diagnostic laboratories.     

Lectins as markers for eosinophilic leukocytes

Summary Lectin from Griffonia simplicifolia (GSA-I) and soybean (SBA) are reliable markers for human eosinophils. In this study we have shown that fluorochrome labeled GSA-I and SBA can be used for specific labeling of eosinophils in paraffin embedded tissue sections, in peripheral blood smears and in cell suspensions prepared for flow cytometry. These two lectins are useful diagnostic reagents which could be applied for further characterization of cytoplasmic components selectively found in human eosinophils.     

Lectins as markers for eosinophilic leukocytes

Lectin from Griffonia simplicifolia (GSA-I) and soybean (SBA) are reliable markers for human eosinophils. In this study we have shown that fluorochrome labeled GSA-I and SBA can be used for specific labeling of eosinophils in paraffin embedded tissue sections, in peripheral blood smears and in cell suspensions prepared for flow cytometry. These two lectins are useful diagnostic reagents which could be applied for further characterization of cytoplasmic components selectively found in human eosinophils.     

Cerebrospinal fluid eotaxin and eotaxin-2 levels in human eosinophilic meningitis associated with angiostrongyliasis

Eosinophilic meningitis associated angiostrongyliasis (EOMA) is a harmful disease of the brain and spinal cord caused by a parasitic helminth, Angiostrongylus cantonensis, presenting with severe headaches and cerebrospinal fluid (CSF) eosinophilia. However, the immunologic pathophysiology especially in relation to the eosinophilic inflammation is still unknown. We measured the CSF concentrations of eotaxin and eotaxin-2 of 30 patients and 10 controls. The CSF eotaxin and eotaxin-2 levels of the EOMA patients were significantly higher than those of the controls (p<0.001). The positive detection values were 83.3% (25/30) and 93.3% (28/30) for eotaxin and eotaxin-2, respectively. CSF eotaxin-2 levels also correlated with CSF eosinophilia (p=0.002). These results might indicate that the recruitment of eosinophils to the brain and spinal cord in EOMA patients could be related to elevated eotaxin-2 levels.     

Angiostrongylus cantonensis: efficacy of albendazole-dexamethasone co-therapy against infection-induced plasminogen activators and eosinophilic meningitis

Angiostrongyliasis is one of the common causes leading to eosinophilic meningitis. Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) may play a role in the pathogenesis. Administration of steroid drugs has been reported to possibly relieve the symptoms of eosinophilic meningitis. This study evaluates the curative effects of albendazole-dexamethasone co-therapy on eosinophilic meningitis in BALB/c mice. Assay indicators for the therapeutic effect include worm recovery, histopathological score of meningitis, tPA, uPA, total protein, and leukocyte counts. The results show that the albendazole-dexamethasone co-therapy significantly decreased (P<0.05) these factors after treatment on day 5 post-inoculation (PI), in contrast to treatment on 15 PI. Thus, the timing of medication is important and is closely related to the anthelmintic efficacy of a drug. At the same dosage and days post-infection, the earlier administration shows better results. This study showed that albendazole-dexamethasone co-therapy is an effective approach for the treatment of parasitic meningitis.     

Angiostrongylus cantonensis eosinophilic meningitis: A clinical study of 42 consecutive cases in French Polynesia

IntroductionIn endemic areas, eosinophilic meningitis is mainly caused by Angiostrongylus cantonensis. We describe a series of this poorly-known condition.MethodsRetrospective cohort study (2000–2012) including all patients diagnosed with eosinophilic meningitis in French Polynesia.ResultsForty-two patients (males: 61.9%, age: 22 (IQR 17–32)) were diagnosed with a serologically proven (n = 13) or probable A. cantonensis meningitis, mostly during the dry season (66.6%) and following the consumption of or prolonged contact with an intermediate/paratenic host (64.3%). No differential diagnosis was found in probable cases, in whom serological tests were performed earlier (7.5 days (6.5–10)) compared to positive patients (7.5 (6.5–10) versus 11 (7–30) days, p = 0.02). The most commonly reported symptom was headache (92.8%). Fever (7.1%) and biological inflammatory syndrome (14.3%) were rare. Blood eosinophil count was 1200/mm³ (900–2548). Cerebrospinal fluid (CSF) analysis disclosed a protein level of 0.9 g/L (0.7–1.1), a CSF/plasma glucose ratio of 0.50 (0.40–0.55), and 500 leucocytes/mm³ (292–725; eosinophils: 42.0% (29.5–60); lymphocytes: 46.5% (32.5–59.0)). Thirteen cases (31.0%) were severe, with 11 focal neurological deficits. A delayed hospital referral (OR 1.13, p = 0.05) was associated with severity.ConclusionsA. cantonensis meningitis must be evocated in young patients with meningitic syndrome, severe headache, and CSF inflammation with predominance of eosinophils.