Edited by: U. K. Misra, Sanjay Gandhi Post Graduate Institute of Medical Sciences, India
Reviewed by: Zafar Neyaz, Sanjay Gandhi Post Graduate Institute of Medical Sciences, India; Kenichi Oishi, Johns Hopkins University, United States
Specialty section: This article was submitted to Neuroinfectious Diseases, a section of the journal Frontiers in Neurology
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Human toxocariasis is one of the most prevalent helminthiases worldwide.
Human toxocariasis is a parasitic zoonosis caused by the larval stages of the ascarids
Asymptomatic CNS infection is probably common, clinically apparent neurotoxocariasis consists of a wide spectrum of neurological manifestations from meningitis, encephalitis, and myelitis, to cerebral vasculitis (
Neurotoxocariasis is not a frequent diagnosis and it is probably underdiagnosed due to the non-specific nature of its symptoms (seizures and headache) exacerbated by a lack of confirmatory diagnostic tests. Diagnosis of neurotoxocariasis is based on the presence of a high titer of anti-
A variety of brain imaging findings have been reported in relation to neurotoxocariasis, initially using computed tomography and more recently, using magnetic resonance imaging (MRI). Despite the evident importance of characterization of neuroimaging findings, few studies have evaluated neurotoxocariasis by MRI. We carried out a systematic review to investigate the clinical manifestations, management options, and MRI characteristics of cerebral toxocariasis.
We used the following search strategy (((“toxocariasis”) OR (“toxocariosis”) AND “central nervous system”) OR “neurotoxocariasis”) OR (“
Since the first reported case of neurotoxocariasis who underwent a brain MRI, published in 1991, we identified 48 articles (
Isolated myelitis represents the most commonly reported presentation, occurring in 70 cases [61 men (87.1%); mean age 45.1 ± 9.8 years] (
The majority of cases were reported in three different case series including 17, 8, and 31 cases (
On MRI, spinal toxocariasis is characterized by swelling and enlargement of the involved spinal segment and hyperintensity on T2 and FLAIR sequences with focal nodular enhancement after gadolinium injection (Figure
Myelitis (
Encephalomyelitis (
ELISA for anti-
Mild–moderate blood eosinophilia was reported in 36 cases (51.4%) while CSF analysis was performed in 62 cases of whom only 21 (33.9%) presented with CSF eosinophilic pleocytosis (Table S1 in Supplementary Material; Table
Blood and CSF characteristics.
Myelitis ( |
Cerebral toxocariasis ( |
|
---|---|---|
Peripheral eosinophilia | 36/70 (51.4%) | 28/33 (84.9%) |
CSF pleocytosis | 21/62 (33.9%) | 19/29 (65.5%) |
Positive serum ELISA | 69 |
32/32 |
Positive serum western blot (WB) | 29/32 (90.6%) | 8/8 (100%) |
Positive CSF ELISA | 38/38 (100%) | 18 |
Positive CSF WB | 20/20 (100%) | 8 |
Biopsy | 1/70 (1.4%) | 6/34 (17.6%) |
Fifty-four patients (77.1%) received anthelmintic treatment (albendazole in 50 cases), almost always with concomitant corticosteroid therapy (
Changes in antibody titers after treatment were only evaluated in a few cases and at different follow-up times with conflicting results (
Encephalic localization has been reported in 34 patients [18 men (54.5%); mean age 33.5 ± 21.3 years]; 2 patients were classified as meningitis (
Encephalic/meningeal toxocariasis involvement was associated with a wide range of clinical manifestations including headache, seizures, focal deficits, confusional state, and cognitive impairment, with or without fever. A case of obstructive hydrocephalus due to toxocariasis was reported in a 46-year-old man who developed headache, diplopia, and visual deficits (
Magnetic resonance imaging findings are not specific, showing single or multiple subcortical, cortical, or white matter hyperintense lesions on FLAIR and T2WI, usually isointense or hypointense in T1WI (Figure
Anti-
A mild–moderate eosinophilia was reported in 28 cases (84.9%); CSF analysis was performed in 24 patients of whom 17 had CSF pleocytosis (14 with eosinophilic pleocytosis). IgE levels were reported only in five patients and were elevated in four (Table S1 in Supplementary Material).
The diagnosis of encephalic/meningeal neurotoxocariasis was confirmed by biopsy in six cases (
Twenty-three patients were treated with anthelmintic medications; seventeen received albendazole while the others received thiabendazole, mebendazole, or diethylcarbamazine. Fifteen of these patients were treated with concomitant corticosteroids. Clinical improvement with complete recovery was observed in all except two patients who suffered a relapse. The only death occurred in a 46-year-old woman with meningoencephalitis (
Toxocariasis is highly prevalent; however, neurotoxocariasis is rarely taken into account as a differential diagnosis in clinical settings. The diagnosis of neurotoxocariasis is a challenge because there is no distinct clinical syndrome. Imaging studies reported to date are not specific and serology has low specificity and sensitivity. In many reports, the diagnosis was only presumptive. Definitive diagnosis is given by histological confirmation, which is rarely available. Our systematic review demonstrated an impressive variation in case definitions and diagnostic evaluations. MRI findings in this large population were all suggestive, but none of them can be considered specific to neurotoxocariosis, and most of these findings can be seen in many other infectious or inflammatory conditions.
About 40% patients were diagnosed on the basis of serum IgG antibody detection by ELISA only. A positive IgG ELISA in serum to confirm the diagnosis may be of minimal value because of seroprevalence of 90%, particularly in tropical areas, and the ELISA frequently cross-reacts with other nematode infections (
On the other hand, peripheral eosinophilia was present in 64% and CSF pleocytosis in 40%. Their absence thus does not exclude CNS
A diagnosis of neurotoxocariasis is also supported by clinical and MRI improvement after specific anthelmintic treatment. In 90% or more of cases, the drug used was albendazole. However, there are no specific guidelines for the treatment of neurotoxocariasis. Patients were treated with anthelmintics and corticosteroids in different dosage and administration schedules. In some cases, the improvement may have resulted from corticosteroid treatment that represents the first-line drug for several autoimmune inflammatory conditions characterized by similar MRI findings and thus would not necessarily support the diagnosis of neurotoxocariasis. Moreover, spontaneous remission has also been reported.
It follows that for a significant proportion of reported neurotoxocariasis cases, other infectious, particularly, parasitic or inflammatory etiologies cannot be definitively ruled out. In particular, in the case of myelitis, which comprised nearly 70% of the identified cases, other causes of autoimmune myelopathies should be suspected. Autoimmune myelopathies are a heterogeneous group of immune-mediated spinal cord disorders encompassing myelopathies with an immune attack on the spinal cord (e.g., aquaporin-4-IgG seropositive neuromyelitis optica), myelopathies occurring with systemic autoimmune disorders, paraneoplastic autoimmune myelopathies, postinfectious autoimmune myelopathies, and myelopathies considered to be immune related (e.g., multiple sclerosis and sarcoidosis) (
Likewise, concerning cerebral toxocariasis, MRI often reveals the presence of a granulomatous process leading to reversible single or multiple ring-enhancing lesions. However, ring-enhancing lesions are a common finding that can be related to different disease processes such as infective, neoplastic, and inflammatory conditions. In particular, single enhancing lesions (SEL) represent a frequent diagnostic dilemma in tropical countries where they are generally due to infectious diseases such as neurocysticercosis and tuberculosis. In
In conclusion, due to the lack of widely accepted, standard diagnostic criteria, there is a great variability in case definitions, diagnostic procedures, and diagnostic certainty for neurotoxocariasis. As suggested by data from animal models, larvae often migrate to the brain and neurotoxocariasis is probably less rare than assumed; like many tropical infectious diseases, it is often neglected and rarely diagnosed. MRI findings include single or multiple subcortical, cortical, or white matter hyperintense lesions, best visualized on FLAIR and T2-weighted imaging, and usually isointense or hypointense on T1. These imaging findings are suggestive but not specific to neurotoxocariasis. The main clinical manifestations of neurotoxocariasis are myelitis (present in approximately two-thirds of all reported cases), encephalitis, and meningitis. Neurotoxocariasis should be included in the differential diagnosis of cases of meningeal, cerebral, or spinal cord disease of unknown origin.
All authors (SS, HG, and AN) participated in conception and organization of review, literature search, and all stages of writing from initial draft to final product.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer ZN and handling editor declared their shared affiliation.
We are indebted to Dr. Farrah Mateen and Maggie Cochran for their thorough review and edition of this manuscript. SS is supported by FIC-NIH training grant D43TW001140.
The Supplementary Material for this article can be found online at