Neurocysticercosis in the United States

Overview and demographics.

In 1954, Campagna reviewed all published cases of cysticercosis within the United States and found a total of 42 reports since 1857.8 Three years later, White and colleagues highlighted the importance of NCC as a diagnostic and therapeutic challenge in their review of three patients who presented to the Massachusetts General Hospital.9 It was not until the development and proliferation of computerized tomography scanning in the late 1970s, however, that the ubiquity of the disease was discovered and the number of publications on the disease increased.

Table 1 shows the 13 largest case series (n > 20) that have been published on NCC within the United States between 1980 and 2004.10–22⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓ Not discussed are 12 smaller NCC case series and 24 individual case studies that were reported as well (see appendix E-1 on the Neurology Web site at www.neurology.org). These reports are largely concentrated in the southwest United States but include NCC cases from every region of the country. There are a total of 1,494 NCC cases in table 1, but some of the series from California may have included duplicate cases based on overlapping time periods and collections from the same institution. The two series by McCormick et al.11,12⇓ cover a 17-year period at the same institution and were considered as a single study. Among the case series in table 1, there was a male bias with 9 of 10 studies showing a male:female ratio above 1.0. For case series reporting age data of patients with NCC (pediatric series excluded15,19,20⇓⇓), the average age ranged between 24 and 35 years. Diagnostic criteria for NCC were not uniform across studies, and most were published prior to the release of formal diagnostic criteria.23,24⇓ Nonetheless, a combination of the following conditions were utilized for NCC diagnosis for studies in table 1: 1) compatible neuroimaging and epidemiologic history; 2) compatible neuroimaging with positive CSF or serum T solium antibody titers; or 3) surgical pathologic specimen confirming the diagnosis of NCC.

The best data on disease burden come from the epidemiologic surveillance studies. Starting in 1989, California became the first state in the United States requiring reporting of cysticercosis cases to the State Department of Health.17 In 2002, Oregon designated cysticercosis as a reportable condition.22 During the first year of reporting from California, a total of 112 NCC cases were collected. Most cases occurred among immigrants from Latin America. The male:female ratio was 1.5 and the median age was 27 years. Prevalence rates were highest for Hispanics at 1.5 per 100,000 population and lowest among non-Hispanic whites at 0.02 per 100,000 population. Looking at Los Angeles County specifically, Sorvillo et al. reported on cysticercosis surveillance between 1988 and 1990.25 A total of 138 incident cases were found for an average crude annual incidence rate of 0.6 per 100,000 population. Eight NCC cases (5.8%) were fatal. In native-born US patients, 9 (6.5%) cases were likely acquired through travel to Mexico and 10 autochthonous or locally acquired cases (7.2%) were documented. Most of the remainder were Latin American immigrants, and the annual incidence rate among Hispanics was 1.6 per 100,000. More recently, Townes et al. presented data from the Oregon Hospital Discharge Database on patients with a diagnosis of NCC between 1995 and 2000.22 Their group found a mean annual incidence rate of 0.2 per 100,000 general population and 3.1 per 100,000 Hispanic population for the study period. Of the 57 patients with recorded birth data, 72% were born in Mexico, 18% in the United States, and 5% in Guatemala. Interestingly, the incidence rate for Hispanics is higher than that reported from California. While these data are the only population-based estimates to date, Shandera and colleagues believe the figures are low.18 Extrapolating from their data in Houston, they argue that the incidence of NCC throughout the United States among Hispanics is at least 8 to 10 per 100,000 per year with 1,000 new cases of NCC diagnosed each year. Moreover, they assert that more cases could be identified through active case finding programs at facilities serving Latin American indigents as opposed to the passive surveillance system in place in California.

NCC acquired in the United States.

Table 2 displays cases of NCC acquired within the United States.11,12,14,15,17–20,22,25–33⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓ There are a total of 76 such cases that have appeared in the literature since 1980. These case reports reflect disease acquisition in a wide range of locations across the country. Fourteen individual cases occurred in patients under the age of 18, with one study reporting a mean age of 14 years for 10 subjects. Three cases were reported to have traveled briefly to endemic countries, but the duration and timing of both trips made disease acquisition there unlikely.26,31,33⇓⇓ All other cases had no known travel history outside the United States.

Symptoms and location of CNS cysts.

For publications that reported onset symptoms in table 1, seizures (66%) were the most frequent, followed by symptomatic hydrocephalus (16%) and headaches (15%). Other commonly reported onset symptoms included meningitis or encephalitis (12%), focal neurologic deficits (11%), and altered mental status (6%). Regarding location of cysts within the CNS, the majority of cases for which there are imaging data available in table 1 presented with parenchymal cysticercosis (91%). Ventricular cysts were found in 6%, subarachnoid cysts in 2%, and spinal cysts in 0.2%. Four studies in table 1 did not present results of cyst location.13,16,17,22⇓⇓⇓

Risk factors.

Unlike most helminthic agents, cysticercosis can be acquired by person-to-person contact with a T solium carrier. Eggs shed in the stool or on skin are immediately infectious and can be transmitted by close contact.25 These eggs are relatively resistant to adverse environmental conditions and can survive several days outside the body.34 In addition to person-to-person spread, food or fomites contaminated by an infected food handler could serve as a vehicle of infection.

One difficulty in assessing how and when disease transmission occurs is the time variation between exposure to T solium eggs and symptom onset. Months to years may pass prior to the development of neurologic symptoms but reliable data to confirm the incubation period are lacking. A delay in developing symptoms has been supported by data from Dixon and Lipscomb who found that over 300 British soldiers who acquired cysticercosis while stationed in India had a median incubation time of 3.5 years.35 More recent data in immigrants to Los Angeles County revealed that among six native born US patients residing in the county who traveled to Mexico before developing symptoms of NCC, the average estimated incubation period was 10.7 months (range 6 to 22 months).25

Mechanism of spread in several cases in table 2 links case contact with a family member, friend, or housekeeper from an endemic country, usually in Latin America. In other case reports, the mechanism of acquisition is unknown. The best studied instance of acquisition of NCC in the United States involved four unrelated Orthodox Jewish families in a New York City community.31 The four individuals who acquired the disease never ate pork, and only one traveled briefly to an endemic country. The most likely sources of infection were T solium eggs transmitted by live-in housekeepers who had recently emigrated from Latin American countries. Examination of housekeepers previously employed in the four case homes revealed an active T solium infection in one and a positive serologic test in another. A follow-up seroprevalence study of the same New York City community found 1.3% (23/1,789 persons from 612 families) to be positive for cysticercosis antibodies.36 All 23 persons were asymptomatic and had no abnormal neuroimaging findings. Seropositivity was significantly associated with female sex, hiring a housekeeper for childcare duties, and with employees from Central America. Overall, the exposure of this community to cysticercosis is surprisingly high, with the widespread employment of house workers from endemic regions largely contributing to exposure risk.

Risk factors for transmitting and developing NCC have been quantified from two surveillance studies within the United States. In Los Angeles County, T solium eggs were significantly more likely to be recovered from stool specimens from household contacts of NCC subjects as compared to community controls (OR = 5.8).25 Carriers were identified in 1.1% of the household contacts of NCC cases between 1988 and 1990. Among individuals who presented with seizures to a network of 11 university-affiliated urban US emergency rooms, those who had positive T solium serology were significantly more likely to be Hispanic (relative risk = 8.7), have visited an endemic region (relative risk = 6.8), be uninsured (relative risk = 2.5), and have an abnormal cranial CT scan (relative risk = 1.7).37 These results reinforce the value of performing a thorough travel history and contact history and obtaining stool specimens on potential carriers as a part of every NCC case evaluation.

Treatment of NCC.

Therapy directed at the parasite itself is related to the stage, location, and number of parasites within the CNS. The majority of therapeutic trials have dealt with parenchymal NCC, the most common form of the disease. Prior to the introduction of antiparasitic drugs in the late 1970s, the only treatment for NCC was surgical. Praziquantel was the first effective antiparasitic agent demonstrated but its use has been eclipsed by albendazole, which has higher parasiticidal efficacy and lower cost.38 It should be emphasized that the major symptom of NCC is seizures, which in most cases responds to monotherapy using first line anticonvulsant medications.

Early treatment studies using antiparasitic medications in parenchymal NCC produced mixed results spurring controversy over their use.39 Treatment advocates point to the reduction of seizures and the ability to manage the dying parasites in a controlled setting along with anti-inflammatory medications.40 They also note that these early studies are not blinded and control groups are inadequate. Alternatively, some authors have argued that killing the parasites does not alter the long term control of seizures in that cysts often die without causing symptoms.41 In addition, antiparasitic treatment may lead to severe cerebral inflammation.

A consensus conference of experts recently reported recommendations for the treatment of NCC based on the current evidence.42 Points of consensus included antiparasitic treatment for parenchymal NCC with a moderate number of live cysts (more than 5), and for subarachnoid cysts. In cases of cysticercotic encephalitis, antiparasitic therapy may worsen the course and is not recommended. Calcified cysticerci represent the terminal phase of cyst devolution and treatment provides no clear benefit. Surgical removal of cysts remains the treatment of choice for cysts in the ventricles, spinal cord along with ventricular shunt placement for hydrocephalus. There was not enough evidence for consensus treatment guidelines on mild parenchymal NCC with fewer than five viable cysts and mild to moderate parenchymal NCC with enhancing lesions (degenerating cysts).

A recent double-blind, placebo-controlled trial has provided more support for the benefits of treating parenchymal NCC.43 In the study, Garcia et al demonstrated that albendazole is safe and effective in decreasing the burden of parasites and reducing the number of generalized seizures.

While much attention has been given to the management of viable and degenerating cysts in NCC, chronic calcified NCC has been relatively neglected. A recent report provides evidence that this terminal form of the disease is not as benign as once thought.44 Calcific NCC has been implicated as a common cause of seizures and other focal symptoms. Perilesional edema often accompanies calcified lesions, but the mechanisms that produce this change are unclear. To better understand the epidemiology, pathophysiology, and management of calcified NCC, more longitudinal and controlled studies are needed.