Neurocysticercosis (NCC), caused by the larval stage (cysticercus) of the pork tapeworm Taenia solium, primarily involves the central nervous system and is the most common cause of acquired epilepsy in the developing world. NCC is endemic to many countries but in Italy, as in Western Europe in general, the few cases reported are mostly imported from endemic areas.[2-4]
Background. Neurocysticercosis (NCC) is an important cause of adult-onset seizures in endemic areas, whereas it is emerging in some nonendemic areas as well because of extensive immigration.
Method. We describe three cases of imported NCC recently admitted to San Bortolo Hospital in Vicenza, located in Northern Italy.
Results. All patients were immigrants. One patient was human immunodeficiency virus positive with severe immunosuppression. The diagnosis of NCC was made on the basis of magnetic resonance results; failure of anti-Toxoplasma, antitubercular, and antifungal therapy; and regression of the cystic lesions after empiric therapy with albendazole. Serology was positive in only one case. In one patient, NCC was diagnosed by biopsy of the brain lesion.
Conclusion. In nonendemic countries, NCC should be included in the differential diagnosis of all patients coming from endemic areas with seizures, hydrocephalus, and compatible lesions on brain imaging. Long-term follow-up is required but may be difficult to implement because these patients tend to move in search of employment. Screening of patient's household contacts for Taenia solium infection should always be carried out.
Methods and Results
We describe the complex presentation of three cases of NCC, one of which occurred in a human immunodeficiency virus (HIV)-positive patient. The difficulties of the diagnostic and clinical management process and the increasing relevance of this imported infection outside the endemic areas are discussed.
A 34-year-old man from Senegal, who had been living in Italy for 6 years, was admitted to San Bortolo Hospital, Vicenza, Italy, in February 2010 because of seizures, of which he had a history since 2008.
Magnetic resonance (MR) in T1- and T2-weighted images (WIs) showed a brain lesion consisting of two adjacent cysts isointense with the cerebral spinal fluid (CSF), surrounded by edema, and showing ring enhancement after gadolinium (Figure 1A–C). The serology for T solium both on serum and CSF was negative (Immunoblotting, LD Bio, Lyon, France performed at the Parasitology Laboratory, San Matteo Hospital Foundation, Pavia, Italy), as was ova and parasite (O&P) fecal examination. No further lesions compatible with parasitic infections were found, with the possible exception of a pulmonary nodule and a single calcification in the right hepatic lobe on ultrasound. Fundoscopic examination was negative.
The cerebral lesion was surgically removed in April 2010 and its pathological examination showed a T solium viable larva and degenerated parasitic material within a cystic cavity (Figure 1D). After surgery the patient was treated with albendazole 400 mg bid for 8 days, praziquantel 1.5 g once on the fourth day, dexamethasone 4 mg bid for 8 days, and carbamazepine 200 mg tid (the latter started before neurosurgery).
A 24-year-old African HIV-2-positive man from Burkina Faso, an observant Muslim, who had been living in Italy for 8 years, was admitted to San Bortolo Hospital in May 2010 with fever, pneumonia, and sepsis. He had an extremely low CD4 count (24 /mm3).
During hospitalization the patient had a seizure. A computed tomography (CT) scan of the brain revealed a hypodense cortical–subcortical lesion in the left frontal-basal lobe, whereas a previous brain CT examination done in June 2009 after a car accident showed a negative result. MR (Figure 2A and B) revealed two adjacent cysts, isointense with CSF in T1-WI and T2-WI, surrounded by edema and ring enhancement after gadolinium. Empirical anti-Toxoplasma therapy with sulfadiazine/pyrimethamine and antifungal and antitubercular therapy were ineffective, and after a repeat MR scan with unchanged findings (Figure 2C), NCC was suspected. Serology for Toxocara canis, Echinococcus granulosus, Toxoplasma gondii, Schistosoma spp., Strongyloides stercoralis (IgG, indirect fluorescent antibody test), Coxiella burnetii, Aspergillus spp., and Bartonella spp., and circulating antigens for Cryptococcus and Cytomegalovirus were negative, as were QuantiFERON-TB test and O&P fecal examination. Serology for T solium was also negative (immunoblotting on serum and CSF, LD Bio, Lyon, France, performed at the Parasitology Laboratory, San Matteo Hospital Foundation, Pavia, Italy). The low platelet count precluded cerebral biopsy; therefore, the patient was started on empiric treatment with albendazole 15 mg/kg in two divided doses plus low-dose steroidal therapy with dexamethasone 4 mg bid. An ophthalmologic evaluation including funduscopic examination was performed before and after treatment started, with a negative result. The therapy was well tolerated and no paradoxical reactions occurred. After 48 days of treatment, near-complete disappearance of the brain lesion was seen on MR (Figure 2D). The serology for T solium was repeated 6 months after treatment (ELISA IgG Tenia Solium, DRG Instruments, Marburg, Germany, and Immunoblotting, LD Bio, performed at the Parasitology Laboratory, Don Calabria Hospital, Negrar, Verona, Italy) which again returned negative.
A 55-year-old woman born and raised in Brazil, previously diagnosed with NCC and treated with ventriculo-peritoneal drainage in 1999 in her country, was admitted to San Bortolo Hospital following progressive loss of consciousness in February 2012.
A brain CT scan showed hydrocephalus, multiple small calcifications in the cerebral parenchyma, and inhomogeneous space-occupying lesions in the cerebellum (Figure 3A and B) and in the right parietal-occipital area. MR showed a cystic lesion surrounded by marked edema in the cerebellar vermis (Figure 3C) and confirmed the hydrocephalus (Figure 3C) and right parietal-occipital cystic lesion surrounded by edema (Figure 3D). Serology for T solium returned positive in serum and liquor in two repeated tests (ELISA Ig G Tenia Solium, DRG Instruments, and Immunoblotting, LD Bio, performed at the Parasitology Laboratory, Don Calabria Hospital, Negrar, Verona, Italy). Analysis of the CSF showed signs of disruption of blood-brain barrier (proteins 72 mg/dL and WBC 300/field, mainly lymphocytes). No ocular localizations were found during the fundoscopic examination.
The patient underwent surgical replacement of the ventricular drainage and medical therapy with intravenous dexamethasone 4 mg bid and oral albendazole 15 mg/kg/day in two divided doses for 1 month. The neurological conditions improved quickly, no paradoxical reactions to the treatment were recorded, and on discharge she did not show any neurological deficit. A follow-up was strongly recommended on her return to Brazil.
Human NCC is considered a rare disease in Italy, but the last review on Italian cases dates back to 1986, and although notification of T solium infection and/or NCC in humans is mandatory in Italy, there is no national register for human cases. Seven autochthonous and 27 imported cases of NCC were reported in Italy from 1990 to 2011.
The infection with the adult parasite is often long-lasting and asymptomatic, and the cystic larval forms can persist in the brain for years without causing symptoms, which may eventually develop, most of the times as a consequence of cyst degeneration and induction of perilesional inflammation.[7, 8]
In patient 1, the long period between immigration and development of seizures is not surprising; particularly, in the case of a single granuloma, seizures can be considered a late manifestation of a disease acquired many years before. On the contrary, patient 2, who had a previous negative CT scan in 2009, could have been infected in Italy. Indeed, carriers of T solium may represent the source of the infection in nonendemic countries, particularly for close contacts, in the absence of infected swine in the territory.[4, 10, 11]
The diagnosis and treatment of NCC are complex and made more difficult owing to the poor knowledge of this disease in nonendemic countries. Moreover, even when NCC is suspected, a negative serology does not rule out the infection, as patients with only one lesion are often seronegative. In a review of case reports and case series of patients with single cysticercus granulomas in nonendemic areas, 41% of cases had a negative serology. The behavior of serology in HIV-positive patients is also still unclear.[13, 14] In these cases, the importance of repeating the serological tests after treatment of a seronegative case to detect seroconversion has been pointed out, but it was not diagnostic in our case. To make matters worse, T solium serology is not available in many European centers, including our hospital; therefore, samples need to be sent to a referral laboratory.
The imaging of brain lesions is the cornerstone of NCC diagnosis. The epidemiology of brain lesions varies between geographical areas, with single lesions being mainly found in India and multiple cysticerci in different stages being found in Asia, Africa, and Latin America. In our series, this is the case in patient 3, from Brazil, while the limited number of cysts in the patients from Sub-Saharan Africa may result from mild infection. A set of diagnostic criteria to classify NCC cases as definitive or probable has been formalized by a group of experts. All three cases were accordingly classified as definitive NCC (Table 1).
|Age/gender||Country of origin||Length of immigration||Clinical presentation||Classification||Neuroimaging||EITB||Comorbidities||Treatment|
|Case 1||34 years/M||Senegal||8 years||Recurrent seizures||Single parenchymal lesion, active||Single viable parenchymal lesion with two adjacent cysts, edema||Negative on serum and CSF||—||Surgery and steroids, ABZ (8 days), and PZQ (single)|
|Case 2||24 years/M||Burkina Faso||6 years||Single seizure, delirium||Single parenchymal lesion, active||Single viable parenchymal lesion with two adjacent cysts, edema||Negative on serum (before and after therapy)||HIV2/AIDS||Steroids and ABZ (60 days)|
|Case 3||55 years/F||Brazil||1 month||Lethargy, intracranial hypertension, meningoencephalitis||Multiple parenchymal active and calcified lesions, extraparenchymal NCC||Multiple cerebral lesions, calcified nodules, intraventricular cyst, ventricular dilatation||Positive on serum and CSF||—||Ventricular drainage, steroids, and ABZ (28 days)|
The differential diagnosis of NCC includes noninfectious (neoplasm, vascular malformations, and scars) and infectious lesions [bacterial or fungal abscess, neuro-toxoplasmosis, cerebral toxocariasis, cryptococcosis, tuberculosis (TB), and strongyloidiasis]. NCC in HIV-infected patients poses the most difficult problems in the differential diagnosis and in the therapeutic approach, as different pathogens can coexist and produce cerebral lesions having similar appearance on CT and MR. In HIV-positive patients with a CD4 count <200/mm, toxoplasmosis is the most frequent cause of cerebral necrotic lesions. However, these are more often multiple and lack a clear cystic appearance. The lack of response to anti-Toxoplasma therapy can be a valid diagnostic aid, while the result of serology for Toxoplasma can be misleading. Massive infections with Mycobacterium tuberculosis and Strongyloides stercoralis are other possible causes of cerebral lesions.[18, 19] In our case, these etiologies were ruled out by serology, unsuccessful TB treatment, and stool examination. Although S stercoralis serology can be negative in immunocompromised patients with hyperinfection syndrome and disseminated strongyloidiasis, treatment with albendazole is generally poorly effective, and gastrointestinal and cutaneous symptoms are more frequent.[19, 20] Albendazole and praziquantel are commonly used to treat active NCC and treatment should be based on NCC staging and presence or absence of eye involvement, taking into account both the risk of adverse reactions after treatment due to inflammation exacerbation and the benefit of treatment in patients with recurrent seizures.[6, 21, 22] Patient 1 received pharmacological therapy after surgery, therefore a short treatment was considered appropriate. In HIV patients, treatment of cerebral parenchymal abscesses is recommended to avoid the development of a calcified lesion,[23, 24] and the concomitant use of steroids is mandatory in these cases to reduce the risk of a paradoxical reaction. Furthermore, a long-term treatment was chosen in this case given the presence of a viable lesion[26, 27] and the patient's general condition.
Finally, in patient 3, emergency drainage was needed prior to any other therapy because of mental impairment due to ventricular dilatation. Treatment with dexamethasone and albendazole with a prolonged course of 4 weeks was decided in this case of extraparenchymal NCC, which is known to have an aggressive behavior, and to reduce the edema and avoid the complications of arachnoiditis.
NCC should be included in the differential diagnosis of seizures, hydrocephalus, and compatible lesions on brain imaging in nonendemic countries, especially in patients from endemic areas, and in their household contacts.[11, 30] In developed countries, the risk of autochthonous transmission is small because of the high hygienic standards and control of meat production; however, household contacts of people carrying T solium are at higher risk. The absence of pork consumption should not be a sufficient epidemiological element to exclude NCC. Indeed, the source of infection in these cases is most likely a contaminated food source, such as a contaminated handler, and in any case all household contacts of diagnosed NCC should be tested for infection. Unfortunately, this is not always possible because of the high mobility of immigrants. For the same reason, a long-term follow-up is difficult to obtain.
NCC should always be included in the differential diagnosis of brain lesions in HIV-positive patients especially if empiric antitoxoplasmosis therapy fails, and the interactions between NCC and HIV deserve further study.
We are particularly grateful to Sam Goblirsch, MD, for reviewing the manuscript. We also thank the Department of Neuroradiology, Vicenza Hospital and Daniela Danieli, MD, for providing the images and Alessandro Segna, MD, for reviewing the neurosurgical aspects.
Declaration of Interests
The authors state that they have no conflicts of interest.