Abstracts

ARTIGO DE REVISÃO REVIEW ARTICLE

Toxocariasis of the central nervous system: with report of two cases

Toxocaríase do sistema nervoso central: com descrição de dois casos

Sandra F. Moreira-Silva^I; Murilo G. Rodrigues^I; João L. Pimenta^I; Camila P. Gomes^I; Larissa H. Freire^I; Fausto E.L. Pereira^II

^IHospital Infantil Nossa Senhora da Glória, Vitória, ES

^IINúcleo de Doenças Infecciosas do Centro Biomédico da Universidade Federal do Espirito Santo, Vitória, ES

^{Correspondence} Correspondence to Dr. Fausto E.L. Pereira Núcleo de Doenças Infecciosas/CBM/UFES Av. Marechal Campos 1468 29040-091 Vitória, ES, Brasil Fax: 55 27 235-7206 e-mail: felp@ndi.ufes.br

ABSTRACT

Clinical involvement of the nervous system in visceral larva migrans due to Toxocara is rare, although in experimental animals the larvae frequently migrate to the brain. A review of the literature from the early 50's to date found 29 cases of brain involvement in toxocariasis. In 20 cases, various clinical and laboratory manifestations of eosinophilic meningitis, encephalitis, myelitis or radiculopathy were reported. We report two children with neurological manifestations, in which there was cerebrospinal fluid pleocytosis with marked eosinophilia and a positive serology for Toxocara both in serum and CSF. Serology for Schistosoma mansoni, Cysticercus cellulosae, Toxoplasma and cytomegalovirus were negative in CSF, that was sterile in both cases. Improvement of signs and symptoms after specific treatment (albendazole or thiabendazole) was observed in the two cases. A summary of data described in the 25 cases previously reported is presented and we conclude that in cases of encephalitis and myelitis with cerebrospinal fluid pleocytosis and eosinophilia, parasitic infection of the central nervous system should be suspected and serology should be performed to establish the correct diagnosis and treatment.

Key-words: Toxocariasis. Toxocara canis. Eosinophilic meningitis. Eosinophilic encephalitis.

RESUMO

Envolvimento do sistema nervoso, com manifestações clínicas, na infecção pelo Toxocara é raro, embora, nos modelos experimentais a larva freqüentemente se localize no sistema nervoso central. Uma revisão da literatura a partir de 1956, quando a síndrome foi descrita, até 2002, mostrou a publicação de 29 casos de neurotoxocaríase, dos quais em 20 havia relato de alterações clínicas e laboratoriais indicativas de meningite, ou encefalite, ou mielite ou radiculite eosinofílicas. Nessa comunicação estamos relatando observações em duas crianças que apresentaram sinais e sintomas neurológicos, com pleocitose e eosinofilia acentuada no líquor e com sorologia positiva para Toxocara no soro e no liquor. Sorologia para Schistosoma mansoni, Cysticercus cellulosae, Toxoplasma e citomegalovirus foram negativas no liquor, que era estéril nos dois casos. Houve melhora dos sinais e sintomas após o tratamento específico (albendazol e tiabendazol) nos dois casos. É apresentado um sumário dos principais achados nos casos relatados na literatura e se conclue que em casos de meningite, encefalite ou mielite com líquor apresentando pleocitose com eosinofilia acentuada, a suspeita de infecção parasitária deve ser levantada, sendo necessário sorologia especifica para diagnóstico e tratamento adequados.

Palavras-chaves:Toxocaríase. Toxocara canis. Meningite eosinofílica. Encefalite eosinofílica.

The expression visceral larva migrans was first used by Beaver⁵ to describe the syndrome associated with any infection caused by paratenic nematode larvae that migrate through organs. Although no consensus has been reached, some authors include the unusual migration of any nematode larvae, including those that naturally infect humans, as visceral larva migrans⁴⁴. The syndrome is typically expressed by fever, persistent eosinophilia, hepatomegaly and pulmonary symptoms and usually results in a benign self-limited course⁵.

Central nervous system involvement in visceral larva migrans syndrome is usually infrequent, but frequency can vary with different species of migrating larvae. Clinical involvement of the nervous system in visceral larva migrans due to Toxocara is rare, although in experimental animals the larvae frequently migrate to the brain ⁶.

The frequency and localization of Toxocara larvae in the central nervous system in humans is unknown. Autopsy studies of isolated cases have revealed Toxocara larvae in leptomeninges ⁷, gray and white matter of cerebrum and cerebellum^{15 26 27 40,} thalamus⁴ and spinal cord⁷. Most of these cases did not present clinical neurological signs. For this reason the clinical significance and true frequency of cerebral localization of Toxocara larvae in non-fatal cases remain unclear. At the Children's Hospital Nossa Senhora da Glória, in Vitoria, where the frequency of positive serology for Toxocara is around 30% of admissions²⁸, the frequency of granulomas due to larva migrans in the central nervous system was 0.68% in a random sample of 308 autopsies of children 1 to 15 years old (Musso et al: unpublished data)

Lewis et al²⁰ reviewed 58 cases of visceral larva migrans syndrome and found mention of convulsions in only three patients. In a case control study Magnaval et al²² demonstrated that Toxocara infection is not associated with a recognizable neurological syndrome, although several cases had a positive Western blot for both cerebrospinal fluid and serum. However a significant association between seizures and positive serology for Toxocara has been reported in Italy¹ and in Bolivia²⁹.

A review of the literature from the early 50's to the present date found 29 cases of brain involvement in toxocariasis^{2 3 4 7 8 11 12 13 14 15 17 19 26 27 30 31 34 35 37 38 39 40 43 45 47 48 49}. Of these 28 cases, 20 reported different clinical and laboratory manifestations of eosinophilic meningitis, encephalitis, myelitis or radiculopathy (the main data of each reported case are summarized in Table 1). Here we report two cases of Toxocara infection in which the most prominent manifestations were neurological, with cerebrospinal fluid eosinophilia and positive serology for Toxocara in both serum and cerebrospinal fluid.

CASE REPORTS

Case 1- A five-year-old girl was admitted with a four day flu-like, febrile illness, which was treated with aspirin. Three days later the child complained of abdominal pain and was vomiting with bloody streaks. After admission, endoscopy revealed acute hemorrhagic gastritis and the child received ranitidine. Five days after admission the child was lethargic, with slurred speech, nystagmus, right convergent squint and left deviation of labial commissure. There was paresis of both inferior and superior members, nuchal rigidity and bilateral Kernig and Lasègue responses. There were right paralyses of the VI, VII and XII cranial nerves, urinary retention and fecal incontinence. The cerebrospinal fluid contained: 54mg/dL glucose, 31mg/dL protein and 187 leukocytes/ul (2% monocytes, 41% lymphocytes and 57% eosinophils). The white blood cell count was 4900 leukocytes/ul (band neutrophils 79/ul, neutrophils 4582/ul, eosinophils 711/ul, lymphocytes 2370/ul, monocytes 158/ul). The blood and cerebrospinal fluid were sterile and because of the high level of eosinophils in the cerebrospinal fluid, a hypothesis of a parasitic meningoencephalitis was proposed. Stool examinations revealed larvae of Strongyloides stercoralis, but were negative for other helminths in the five samples examined. Treatment with thiabendazole was initiated. A second lumbar puncture was performed three days after the first puncture, and the results were similar, with a marked eosinophilic pleocytosis. Serology for Toxocara (ELISA IgG with secretory-excretory antigen) was positive in both the serum and cerebrospinal fluid. Serology for Schistosoma mansoni, Cysticercus cellulosae and toxoplasmosis were negative in the cerebrospinal fluid. Cranial MRI (performed 25 days after admission) showed small irregular lesions situated in the posterior portion of the spine-bulbar transition and pedunculus cerebellaris, with hyperintense signal in T2 and DP, but intermediary signal in T1. There was no enhancement after intravenous contrast, nor were there signs of tissue compression. An inflammatory lesion was suggested, most likely produced by Toxocara larvae. After 14 days of thiabendazole the child received albendazole for 10 days. Improvement was evident after the use of albendazole. The child was discharged 36 days after admission with discrete dysarthria and dysmetria and a mild paresis of VI and VII cranial nerves. Six months later the child presented without neurological manifestations.

Case 2 - A five-year-old boy was admitted with palsy of the inferior limbs and urinary retention. Cerebrospinal fluid was clear with 63 mg/dL glucose, 17.5mg/dL proteins and 23 leukocytes/ul (3% neutrophils, 57% eosinophils, 25% lymphocytes and 15% monocytes). The total leukocyte count was 22100/ul( 442 myelocytes, 221 metamyelocytes, 1547 band neutrophils, 15028 neutrophils, 221 eosinophils, 4199 lymphocytes, 442 monocytes). Fecal examination was negative (five samples). Cerebrospinal fluid was sterile and presented negative serology for toxoplasmosis, Schistosoma mansoni and Cysticercus cellulosae. Corticotherapy was started until a positive serology for Toxocara was detected in both the serum and cerebrospinal fluid. Corticotherapy was replaced with thiabendazole for 15 days. Diagnosis of possible transverse myelitis produced by Toxocara larvae was noted. The child was discharged 34 days after admission with partial improvement of palsy. One month later the palsy had disappeared, and the child presented no signs of sequelae.

DISCUSSION

In both cases reported here there were signs of neurological lesions and pleocytosis with eosinophilia in sterile cerebrospinal fluid. In Case 1 MRI showed lesions in the spine-bulbar border and in the pedunculus cerebellaris. The localization of these lesions was compatible with the clinical manifestations. In Case 2 image examination was not performed. Sterile cerebrospinal fluid, with pleocytosis and marked eosinophilia, was an indication of the possible parasitic origin of the neural and meningeal lesions, reinforced by the positive serology for Toxocara.

Neural involvement by Toxocara larvae is highly probable in both cases if one takes into account: a) cerebrospinal fluid pleocytosis with marked eosinophilia; b) positive serology, with IgM anti-Toxocara, in both serum and cerebrospinal fluid, and negative serology for Schistosoma mansoni and Cysticercus cellulosae (parasites that reach the nervous system most frequently in Brazil ); c) sterile cerebrospinal fluid and negative serology for other common infections in the central nervous system such as toxoplasmosis, syphilis and cytomegalovirus; and d) improvement of signs and symptoms after treatment with albendazole and thiabendazole. Furthermore, Toxocara infection is frequent in children that are treated at the Children's Hospital Nossa Senhora da Glória in Vitória²⁸.

These arguments are not irrefutable because eosinophilic meningitis or meningoencephalitis may be idiopathic or produced by larvae of such human helminths (reviewed in reference 19) as Ascaris lumbricoides or Strongyloides stercoralis^{24 25}, Ascaris suum^{16 18 23 32}, Trichinella spiralis¹⁰ or by larvae of other paratenic nematodes such as the rat nematode Angiostrongylus cantonensis^{33 42} and raccoon ascarid, Baylisascaris procyonis³⁴. Since Ascaris antigens can cross react with Toxocara antigens, one could argue that the positive serology observed in the two cases reported here may be due to this cross reaction. However, the serology was performed after absorption with Ascaris antigen. In one case (Case 2) there was Strongyloides stercoralis larvae in the feces. Although there are reports of Strongyloides larvae entering the central nervous system, this occurrence is extremely rare and is associated with the disseminated form of the infection⁹. The other paratenic nematodes that can cause eosinophilic meningitis or encephalitis have not yet been described in Brazil.

As demonstrated in Table 1, neural involvement in toxocariasis has been reported in all ages without a significant gender prevalence. Eosinophilia occurred in both peripheral blood (7/9 cases) and cerebrospinal fluid (8/11 cases) in those cases in which eosinophil counts were reported. It is noteworthy that some cases occurred without presence of eosinophilia in blood and cerebrospinal fluid. Serology is useful for diagnosis although cross reaction is frequent with larval antigens from other nematode species. For this reason absorption of serum or cerebrospinal fluid with larval antigens from other nematode species would improve the specificity of serology. Additionally, further development of methods to detect IgM anti-Toxocara larvae would help to identify recent infection. We conclude that in cases of encephalitis and myelitis with cerebrospinal fluid pleocytosis and eosinophilia, parasitic infection of the central nervous system may be suspicious and serology should be performed to establish the correct diagnosis and treatment.

Recebido para publicação em 4/4/2003

Aceito em 16/2/2004

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