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CASE REPORT
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Neurocysticercosis with Diplopia Responds Well to Albendazole Akihiro Sato 1,2, Itaru Nakamura 1, Hiroaki Fujita 1,3, Shinji Fukushima 1, Yasutaka Mizuno 1, Takeshi Fujii 2 and Tetsuya Matsumoto 3
Abstract We report a case of neurocysticercosis concurrent with taeniasis in a 31-year-old woman. The patient presented with a headache and diplopia. Oculomotor disturbances with a left adduction deficit were observed. Fundoscopy revealed papilledema. Additionally, computed tomography of the brain revealed more than 20 small cysts within the parenchyma, most of which were associated with ring enhancement. Moreover, serum antibody testing (Western blotting) for Taenia solium-cysticerci was positive. The patient received albendazole and corticosteroids, and progressive resolution of the neurological symptoms and papilledema was observed starting approximately three days after administration. This patient has been asymptomatic for more than one year. Key words: neurocysticercosis, cysticercosis, diplopia, albendazole (Intern Med 55: 1219-1222, 2016) (DOI: 10.2169/internalmedicine.55.6176)
Introduction Cysticercosis, an infection caused by the encysted larval stage of the tapeworm Taenia solium, is one of the most common parasitic diseases of the nervous system in humans and constitutes a major public health problem in most of the developing world (1). Millions of people in these areas are infected by cysticerci, and many of them will eventually experience the clinical consequences of this infection (2). Neurocysticercosis usually presents as a seizure or a headache (3), and diplopia is rare. Moreover, anticysticercal therapy has been marked by an intense controversy. We herein report that neurocysticercosis with diplopia responds well to albendazole (ABZ).
Case Report A 31-year-old Cambodian woman married to a Japanese man with no medical history presented with a two-week history of a headache and diplopia. She had gradually started complaining of diplopia, for which she went to the Depart-
ment of Ophthalmology. Fundoscopy revealed papilledema, after which she was sent to the Department of Neurosurgery. Computed tomography (CT) of the brain revealed more than 20 small cysts (Fig. 1) within the parenchyma, which were 4 to 10 mm in diameter; most of these cysts were associated with ring enhancement. She was hospitalized for a brain biopsy and was referred to the Department of Infectious Diseases. A medical history obtained at that time revealed that she had got married at 20 years of age and moved to Japan at that time. She had visited Cambodia three times during the period from 21 to 31 years of age and had spent one week in the country during each visit. While in Cambodia, the patient had stayed with her close family and eaten meals with them on a daily basis, including grilled pork and fresh vegetables, although she had never eaten raw meat or fish. On admission, the patient was not febrile, and other vital signs were normal. A neurological examination showed a conscious patient with intact cognitive functions. Oculomotor disturbances with a left adduction deficit were observed. However, the patient’s sensory abilities and general examination results were normal. A neuro-ophthalmological examination also revealed normal visual acuity bilaterally, with
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Department of Infection Prevention and Control, Tokyo Medical University Hospital, Japan, ２Department of Infection Prevention and Control, Tokyo Medical University Hachioji Medical Center, Japan and ３Department of Microbiology, Tokyo Medical University, Japan Received for publication July 13, 2015; Accepted for publication September 7, 2015 Correspondence to Dr. Itaru Nakamura,
[email protected]
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DOI: 10.2169/internalmedicine.55.6176
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Figure 1. Computed tomography of the brain. There were more than 20 small cysts. (A, B) Axial and (C) coronal section images.
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Figure 2. Magnetic resonance images of the brain showed more than 20 small cysts within the parenchyma and some with perilesional focal edema. (A) Before treatment, T2WI. (B) Before treatment, T1WI. (C) Following a 28-day course of albendazole, nearly all of the lesions had disappeared, T2WI.
intact visual fields on confrontation, although the patient had monocular diplopia. The laboratory test results were nearly normal. Magnetic resonance imaging (MRI) of the brain showed more than 20 small cysts (Fig. 2A, B) within the parenchyma and a degree of perilesional focal edema. In addition, CT from the neck to the pelvis revealed more than 30 subcutaneous calcific lesions (Fig. 3). Histopathological biopsy specimens from lesions on the left back (Fig. 3A) were not diagnostic; although we could observe calcific structures in the subcutaneous tissue by ultrasound, we could not directly confirm the identity of the lesions. Serum antibody testing (Western blotting) for Taenia solium cysticerci, however, was positive at that time. We had hypothesized that the patient’s condition was associated with the complications of Taenia solium infection because of the large number of lesions; hence, gastrography and small-bowel endoscopy were performed, but we did not detect any adult worms. We also did not find taeniid eggs in her stool after examining specimens two times. Nonetheless, we were still able to diagnose neurocysticercosis based on her symptoms, the neuroimaging findings and serum antibody testing without requiring a brain biopsy. The patient received ABZ at a dose of 400 mg twice per day for 28 days (15 mg/kg/day), along with a corticosteroid (prednisolone at 30 mg/day for seven days, 20 mg/day for
seven days and 10 mg/day for seven days). Progressive resolution of her neurological symptoms and papilledema was observed beginning at approximately three days after administration. Magnetic resonance imaging of the brain revealed almost complete disappearance of the parenchymal lesions and perilesional focal edema by the end of the treatment period (Fig. 2C), at which time the anti-epileptic drug was terminated. This patient has been asymptomatic for more than one year.
Discussion Neurocysticercosis occurs when humans become intermediate hosts of the tapeworm Taenia solium by ingesting its eggs from contaminated food or, most often, directly from a taenia carrier (fecal-oral route). These larvae can migrate to any organ in the body, although most reports have focused on cysts located in the central nervous system (CNS), eyes, muscles or subcutaneous tissues. Larvae have been found in several locations in the CNS. This diversity of locations is believed partly to explain the range of clinical manifestations of neurocysticercosis (4). Our patient met the diagnostic criteria for neurocysticercosis, as proposed by Del Brutto (5). The infection in this case was thought to have occurred in Cambodia because
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Figure 3. Computed tomography was performed from the neck to the pelvis. Calcific lesions were found in the (A) lower back, (B) pelvic region and (C) femoral area. There were more than 30 subcutaneous calcific lesions spread throughout the body of our patient.
Taenia solium has historically been distributed only within Okinawa Prefecture in Japan; therefore, the number of endemic neurocysticercosis cases in the country is relatively small. Worldwide, a survey of the literature published between 1981 and 2011 concerning neurocysticercosis among international travelers found 35 reports documenting 52 patients (5). The following three points based on this case are noteworthy. First, this case of neurocysticercosis is very rare in that the chief complaint was diplopia. Second, after performing a biopsy of the subcutaneous calcific lesions, it was difficult to identify the lesions. Third, ABZ might be effective as a therapy for neurocysticercosis. Our patient represents a rare case of neurocysticercosis, even when considering cases worldwide, insofar as her chief complaint was diplopia. The clinical manifestations of neurocysticercosis largely depend on the number, type, size, localization and stage of development of the cysticerci as well as the host’s immune response to the parasite (6, 7). Seizures are the most common manifestations of neurocysticercosis (70 to 90%), followed by headache (38%), focal deficits (16%) and signs of intracranial hypertension (nausea,
vomiting and papilledema) (12%). Other manifestations occur in less than 10% of symptomatic patients and visual changes occur in only 6% of cases (8). In the case described here, papilledema was observed, and the patient had intracranial hypertension. Because the brain CT did not show a mass occupying the abducens nerve, we believe that her diplopia was the result of the associated intracranial hypertension. In neurocysticercosis, neuro-ophthalmological signs are usually the result of associated meningitis or hydrocephalus and present as abducens nerve palsy or optic neuropathy secondary to chronic papilledema (8). However, no reports have so far indicated the rate of diplopia resulting from intracranial hypertension. With increasing global travel, consideration of the possibility of neurocysticercosis in cases of diplopia from areas where Taenia solium remains endemic should lead to a significant decrease in the number of unnecessary brain biopsies. There have been many reports of skin and brain biopsies of flesh and calcified lesions, in contrast to a low number of CT studies of calcification (9-11). Although we performed ultrasonography of the left back (where the lesion was located) before the biopsy, we were not able to find the calcified nodule, despite knowing its position. This difficulty was believed to be attributable to the lesion’s size and color. We also performed a copo-polymerase chain reaction (PCR) analysis of the patient’s peripheral fatty tissue, but the result was negative. We conclude that subcutaneous calcific lesions are difficult to find by a biopsy, and it may be unnecessary when serum antibody testing is positive or other clinical manifestations are consistent with cysticercosis. Randomized controlled trials evaluating the clinical benefit of treatment in such cases have yielded conflicting data, with certain studies indicating a benefit and others failing to show a difference (12, 13). A systematic review by the Cochrane Collaboration concluded that, although evidence from trials in adults with viable cysts suggested that ABZ may reduce the number of lesions, no difference in the recurrence of seizures was detectable (14). The treatment modalities available to patients with neurocysticercosis include surgery, symptomatic therapy and antiparasitic drugs. An individualized combination treatment is considered to be better for each patient based on the cyst location, the level of inflammation and the clinical presentation. Antiparasitic drugs for neurocysticercosis, formerly restricted to use as palliative measures, have recently made dramatic progress with the advent of two drugs that are considered to be effective: praziquantel (PZQ) and ABZ (15, 16). Most comparative investigations have shown that ABZ is more effective than PZQ in reducing the number of cysts and in inducing an overall clinical improvement, with a lower frequency of adverse reactions. In the case described here, we chose ABZ for this reason; however, anticysticercal therapy has been marked by an intense controversy. In this case, there was the destruction of multiple cysts because cysts within the parenchyma were fresh and not calcific (Fig. 2). The headache and diplopia, which were the chief complaints in our case,
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were thought to be attributable to intracranial hypertension, as detected by brain CT. In neurocysticercosis, neuroophthalmological signs are usually the result of associated intracranial hypertension; in the present case, the symptom improvement might have resulted from the use of not only ABZ, but also the administration of steroids. In conclusion, neurocysticercosis in which the chief complaint is diplopia is very rare, and a high index of suspicion for neurocysticercosis remains imperative to avoid an unnecessary biopsy of calcified lesions. With increasing global travel, clinicians must thus consider the possibility of neurocysticercosis in cases of nodular brain lesions in subjects from areas where Taenia solium remains endemic.
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The authors state that they have no Conflict of Interest (COI).
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Acknowledgement We thank Hiroshi Yamazaki and Yasuyuki Morishima, Department of Parasitology, National Institute of Infectious Diseases, for their excellent technical help in serum antibody testing.
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References 1. Nash TE, Garcia HH. Diagnosis and treatment of neurocysticercosis. Nat Rev Neurol 7: 584-594, 2011. 2. Carabin H, Ndimubanzi PC, Budke CM, et al. Clinical manifestations associated with neurocysticercosis: a systematic review. PLoS Negl Trop Dis 5: e1152, 2011. 3. DeGiorgio CM, Medina MT, Durón R, Zee C, Escueta SP. Neurocysticercosis. Epilepsy Curr 4: 107-111, 2004. 4. Del Brutto OH. Neurocysticercosis among international travelers to disease-endemic areas. J Travel Med 19: 112-117, 2012. 5. Del Brutto OH, Rajshekhar V, White AC Jr, et al. Proposed diag-
14.
15.
16.
nostic criteria for neurocysticercosis. Neurology 57: 177-183, 2001. Fleury A, Escobar A, Fragoso G, Sciutto E, Larralde C. Clinical heterogeneity of human neurocysticercosis results from complex interactions among parasite, host and environmental factors. Trans R Soc Trop Med Hyg 104: 243-250, 2010. Takayanagui OM, Odashima NS. Clinical aspects of neurocysticercosis. Parasitol Int 55 (Suppl): S111-S115, 2006. Keane JR. Neuro-ophthalmologic signs and symptoms of cysticercosis. Arch Ophthalmol 100: 1445-1448, 1982. Kobayashi K, Nakamura-Uchiyama F, Nishiguchi T, et al. Rare case of disseminated cysticercosis and taeniasis in a Japanese traveler after returning from India. Am J Trop Med Hyg 89: 58-62, 2013. Giordani MT, Tamarozzi F, Cattaneo F, Brunetti E. Three cases of imported neurocysticercosis in Northern Italy. J Travel Med 21: 17-23, 2014. Yamasaki H, Nagase T, Kiyoshige Y, et al. A case of intramuscular cysticercosis diagnosed definitively by mitochondrial DNA analysis of extremely calcified cysts. Parasitol Int 55: 127-130, 2006. Carpio A, Kelvin EA, Bagiella E, et al. Effects of albendazole treatment on neurocysticercosis: a randomised controlled trial. J Neurol Neurosurg Psychiatry 79: 1050-1055, 2008. Garcia HH, Pretell EJ, Gilman RH, et al. A trial of antiparasitic treatment to reduce the rate of seizures due to cerebral cysticercosis. N Engl J Med 350: 249-258, 2004. Abba K, Ramaratnam S, Ranganathan LN. Anthelmintics for people with neurocysticercosis. Cochrane Database Syst Rev CD000215, 2010. García HH, Evans CA, Nash TE, et al. Current consensus guidelines for treatment of neurocysticercosis. Clin Microbiol Rev 15: 747-756, 2002. Takayanagui OM, Odashima NS, Bonato PS, Lima JE, Lanchote VL. Medical management of neurocysticercosis. Expert Opin Pharmacother 12: 2845-2856, 2011.
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