Corresponding Author: Eric Caumes, MD, Department of Infectious and Tropical Diseases, Pitié Salpêtrière University Hospital, 47–83, Boulevard de l'Hôpital, F-75651 Paris Cedex 13, France. E-mail: email@example.com
We report two cases of symptomatic neurocysticercosis in two migrants whose negative serology delayed appropriate treatment for 9 and 6 months, respectively. Seroconversion occurred after treatment, which was associated with paradoxical reaction in one patient. Long-term outcome was good in both patients.
In Western countries, neurocysticercosis (NCC) is mostly seen in migrants, native to endemic areas, and occasionally in travelers returning from such countries.[1, 2] The diagnosis relies on the association of compatible clinical symptoms, typical images on cranial computed tomography (CT) scan or magnetic resonance imaging (MRI), and positive serodiagnosis.[3-5]
However, serologic tests display a high rate of false negatives[6, 7] Hence, a negative serology can cause futile and invasive procedures to confirm the diagnosis and delay the treatment by months as illustrated in the two following cases.
A 35-year-old man native to South Africa, who moved to France in 2003, was admitted to a French university hospital in October 2009 complaining of headaches and photophobia. Physical examination was normal. Cerebrospinal fluid (CSF) showed no abnormalities. As the symptoms persisted, a cranial MRI was performed and revealed a 6 mm cyst in the occipital region (Figure 1A). Cysticercosis serology with enzyme-linked immunosorbent assay (ELISA; RIDASCREEN Taenia solium IgG, R-Biopharm AG, Darmstadt, Germany) and immunoblot (Cysticercosis western blot IgG, LDB Diagnostics, Lyon, France) were negative in the blood and in the CSF. All radiological, immunological, parasitological, and bacteriological investigations were negative. Therefore, a brain stereotaxic biopsy was performed in November 2009. Histology showed a diffuse lymphocytic infiltrate, mostly positive to CD3 but no cyst or parasitological material and was considered inconclusive. The patient was thus discharged without any diagnosis or treatment. In December 2009, a seizure occurred and the cerebral CT scan revealed the same occipital lesion. Taenia solium serologies with ELISA (RIDASCREEN T solium IgG, R-Biopharm AG) and immunoblot (Cysticercosis western blot IgG, LDB Diagnostics) were still negative. Essential epilepsy was diagnosed and he was treated with levetiracetam 1,000 mg twice a day.
The patient was admitted in our department in June 2010 for a second opinion. Serologies with homemade ELISA and immunoblot (Cysticercosis western blot IgG, LDB Diagnostics) remained negative. The homemade ELISA was described by Kolopp. Briefly, the antigen is prepared with cysticerci of T solium from Madagascar. The whole larvae are prepared as previously described. The microwell plates are coated with the 5 mcg/L antigen solution in carbonate buffer overnight at +4°C. The ELISA is classical. The result is positive if the optical density (OD) at 405 nm is higher than the cutoff. The unit system is based on the positive and negative control OD. The sensitivity of the method has been estimated to 83% in serum and 62% in CSF. As the patient came from a remote part of South Africa, a diagnosis of seronegative NCC was considered and he was treated with albendazole 400 mg twice a day. By the third day of treatment, headaches had increased and he complained of blurred vision and vomiting. Physical examination revealed quadranopsia on the upper left side. A cranial CT scan was done and showed brain edema and mass effect around a ring-enhanced occipital lesion, which is more typical of NCC (Figure 1B). A 7-day corticotherapy course (prednisone 1 mg/kg/d) was initiated with progressive decrease of the daily dose. Vomiting and headaches disappeared within 24 hours. Albendazole was continued for 21 days. Homemade ELISA became positive (30 units; cut off: 10 units) 1 week after the beginning of the treatment as well as the immunoblot (Cysticercosis western blot IgG, LDB Diagnostics) with the appearance of two bands (P6-8 and P39kDa). Photophobia disappeared completely within 8 days, but blurred vision persisted for 6 months. In December 2010, the result of an ophthalmological examination was normal. The cranial MRI, performed in February 2011, showed a significant decrease in the lesion with only a 5 mm calcification persisting in the right occipital region.
A 40-year-old man from Laos, who moved to France in 1979, was admitted to our department in October 2010 for headaches. His medical history revealed epilepsy, with a 20-year history of seizure activity. In addition, he had previously been treated with albendazole (400 mg bid for 1 month) once in 2000 and once in 2003 in another French hospital where the possibility of NCC had been mentioned but not confirmed. He had not traveled to any country endemic for cysticercosis since then. In April 2010, he came to our department still complaining of headaches. A cranial MRI was performed and revealed a new viable cysticercosis cyst (Figure 2), and three enhancing cysts that were not present on the MRI performed 3 years previously. Homemade ELISA and immunoblot (Cysticercosis western blot IgG, LDB Diagnostics) were negative for cysticercosis. He was treated with praziquantel (60 mg/kg/d) because the previous treatment with albendazole seemed to have failed. Treatment was continued for 21 days in association with prednisone (1 mg/kg/d) during the first week. The ELISA (RIDASCREEN) (5 units) and immunoblot (Cysticercosis western blot IgG, LDB Diagnostics) became positive at day 7 with the appearance of three bands (50–55, 23–26, and 6–8 kDa). Headaches decreased within the first week and disappeared within 2 months. He had no seizure activity but his epilepsy treatment (phenobarbital) was continued.
These two cases show the importance of repeated serology in cases of seronegative NCC as the seroconversion may occur within 7 days of the treatment onset.
The diagnosis of NCC can be challenging as illustrated in our two cases. The ELISA test is known to have poor specificity (75.3–95.7%) and sensitivity (41–80%).[6, 7] Of note, the rate of ELISA and enzyme-linked immunoelectro-transfer blot (EITB) false negatives is considered to be higher in patients with a single intracranial cyst. [6, 10] However, for patients with two or more cystic or enhancing lesions, the sensitivity and specificity of EITB have been estimated to be around 81.7 and 99.4%, respectively. Therefore, negative serologies do not rule out the diagnosis.
It is noteworthy that our two patients seroconverted within 1 week of the initiation of treatment. As far as we know, this has not been described before. However, this can be explained easily as antiparasitic therapy is known to damage cysticerci and therefore to expose parasitic antigens to the immune system, inducing antibody production and increased blood levels of antibodies.
The first patient treated with albendazole experienced a paradoxical reaction which is a well-known complication. However, its frequency has so far never been established precisely. Corticosteroids were not given initially because the diagnosis had not been confirmed and the clinical symptoms and cranial CT scan lesions (single occipital lesion) were not considered to be at high risk of severe complications.
The NCC history of the second patient also illustrates the potential risk of recurrence after treatment although we were not able to evaluate if the patient had received the appropriate doses of albendazole. Indeed, new viable NCC cysts appeared on the cranial MRI 3 years later despite the fact that he had not traveled in endemic areas during this time. Perhaps this patient could have been a candidate for T solium eradication, which requires adequate treatment of tapeworm carriers with a single dose of niclosamide (2 g) or praziquantel (5 mg/kg). However, it is also possible that he was re-infested in his household as has been reported in some clusters of NCC.[13, 14] As an example, a follow-up of cysticercosis cases reported in Los Angeles in the 1980s demonstrated at least one active tapeworm carrier among family contacts of 22% of locally acquired cases, and 5% of imported cases. According to the CDC, identification and treatment of tapeworm carriers is an important public health measure that can prevent further cases. Therefore, the CDC recommends that such employees should have stool examinations for taeniasis and be treated if found to be infected.
Every physician should be aware of the risk of NCC in immigrants and travelers with neurological symptoms and know that negative serology does not rule out the diagnosis. If the diagnosis of NCC is likely, a presumptive treatment should be started and the serology should be repeated at least 1 week later in order to confirm the diagnosis.
The authors wish to thank C. Hirsch, MD, for the editorial work.
Declaration of Interests
The authors state they have no conflicts of interest to declare.