Bruce Landres, M.D.

Introduction

Cysticercosis is a parasitic disease commonly found in underdeveloped areas including Mexico, Central America, China, Korea, India and parts of Eastern Europe. While previously uncommon in the industrialized countries, this parasitic infestation is becoming more prevalent in the United States as a result of the recent influx of immigrants.^{1,2,3,4,5,6,7,8,9,10}

Case Report

A 31-year-old man with no recent travels abroad presented with an episode of loss of consciousness in June 1989. His past medical history was significant for three episodes of scintillating scotoma since 1986. At the present occasion, the patient was under duress and had missed lunch. He developed a geometric visual scotoma just before the loss of consciousness. He fell and struck his head and bled significantly from the head wound. He was unconscious for a full 30 minutes. Observers later reported no tongue biting, no incontinence of urine or feces and no tonic/clonic movements. However, the patient was confused and combative upon awakening.

He was seen in the emergency room at his local hospital where a CT scan without contrast and EEG (awake only) were both reported to be normal. Blood count, electrolytes, liver function testing and toxic screen for drugs were all normal. Neurologic consultation showed the patient to be normal and the differential diagnosis was seizure versus syncope.

The patient did well until he presented with another syncopal episode ten months later. He was riding his bike when he developed a scintillating scotoma and lost consciousness. There was no head trauma. An observer at the scene described a seizure, but was unavailable for further history. The patient described no incontinence or tongue biting, but he was confused and disoriented upon awakening. He was again taken to the local emergency room and treated with phenytoin. Neurologic examination in the emergency room and in my office on the following day were both normal.

The patient's EEG, both awake and asleep, was normal. MR with contrast demonstrated a small area of decreased signal intensity on T1 weighted images with isointensity on T2 weighted images in the left occipital pole. The appearance was that of a small cystic lesion with suspicion of a structure within it. The patient declined further evaluation.

The patient's medication was later changed to carbamazepine, but he discontinued it on his own. He did well until August 1991, when he had another episode of loss of consciousness at work and was found to have some "seizure-like" activity. A second MR with gadolinium revealed that the small cystic area was larger than before and surrounded by a ringlike area of enhancement most consistent with either tumor or edema. The neurosurgical consultant felt that this lesion was most consistent with a glioma and recommended stereotactic biopsy followed with craniotomy and resection.

A second neurosurgical consultant suggested the possibility of cysticercosis, and infectious disease consultation was obtained. The patient had blood titers drawn to test for cysticercosis by Western blot. The initial test was negative, but a repeat study 3 weeks later was positive. Cysticercus antibodies IgG, IgM and IgA were all negative. The patient was placed on an empiric trial of praziquantel and prednisone. Three weeks later, MR showed a definitive shrinkage of the cystic lesion with thickening of the capsule. Eight months after treatment, the follow-up MR showed no evidence of the prior lesion. The patient has been off of anticonvulsant medicines since that time and has had no recurrent symptoms.

There was no history of ingestion of any raw pork, but the patient had traveled abroad to Mexico at the age of 15, to France at the age of 29, and to Japan at the age of 30.

Discussion

"Cysticercosis is a systemic infestation of the larval form of the pork tapeworm, Taenia solium."² This is distinct from the intestinal parasite, which is acquired by eating undercooked pork containing encysted cysticercus larvae resulting in the formation of tapeworms within the intestine. In cysticercosis, man serves as an incidental host by ingesting T. solium eggs. These eggs release oncospheres (embryos) that penetrate the intestinal mucosa and spread hematogenously to other organs, most commonly muscles, eyes and the brain. The eggs may have been ingested through auto-inocu-lation in a previously infested individual, fecal-oral contamination by a food handler, or eating contaminated raw vegetables or water.^{1,2,3,7,8,11,12}

In 1995 Moore et al documented an incidence of 1.3% antibody positivity to cysticercus in an Orthodox Jewish community. Epidemiological studies linked the parasitic infestation to domestic food handlers from various Latin American coun-tries.¹³ In 1996 Rosenfeld et al found 76 cases of cysticercosis among children in Chicago. While 96% of the children were of Hispanic heritage, 42% of them were born in the United States.¹⁴ In both studies, the subjects acquired the parasite in the United States, a non-endemic country; moreover, Moore's study demonstrated the prevalence of cysticercosis in a non-pork consuming population.

It is estimated that at least fifty million people suffer from cysticercosis worldwide.⁸ In Mexico some studies have estimated that 2.0-3.6% of the entire population is infested.^2,7,14,15 Some parts of rural South America report rates of 22% seropositivity on blood tests.^1,15 In Latin America, the incidence of cysticercosis has been reported in the range of 2550% among patients with adult onset seizure, and cysticercosis is recognized as a major cause of epilepsy in developing countries.^1,8 Since 1997, more than one thousand cases of cysticercosis have been reported in the United States, and a great number of these cases involves recent immigrants.^6,15 In Southern California, cysticercosis represents approximately 2% of the hospitalizations for neurological disorders at a cost of $8.8 billion in 1994.^6,8

In our particular case, the patient had no apparent risk factors. He traveled to Mexico 16 years prior to the onset of symptoms, and he had not been in contact with any known infested individuals. However, in an earlier study, British soldiers stationed in India were found to have a mean time from infection to the onset of symptoms of 4.8 years, with a range of 2 to 30 ^1,8,12 While our patient falls within this range since his travel to Mexico, it is also possible that he was infected at another time from an infested food handler.

The T. solium embryo develops into a larva and then an encysted cysticercus over a period of two months.¹¹ The cysticercus seems to be able to evade the host's immune system. Once the cysticercus is established in the brain, it is immunologically inert. Thus there is minimal tissue damage and inflammation. During this vesicular stage, a cysticercus may live from 18 months to 10 years without causing symptoms in the infested individual.¹¹

During the subsequent colloid stage, the parasite dies and loses the ability to evade the host's immune system. This leads to acute inflammatory responses with the formation of edema around the cysticercus capsule. This colloid stage is the most likely time for a host to experience epileptic seizures as granulomatous reactions start. Shrinkage and granuloma formation within the brain constitute the nodular-granular phase. Later, the cyst may either reabsorb completely without any residua or calcify in what is called the calcified stage.^3,7,11,15

Cysticercosis is only clinically manifest as the host's immune defenses activate and inflammatory processes begin. "Thus, most, if not all, patients with symptomatic parenchymal neurocysticercosis are infected with parasites that have lost their ability to suppress the host response and are in the process of dying."¹⁵ Grand mal seizures, focal seizure disorders, headaches, other focal neurological deficits, and even strokes have been reported. "Usually patients have partial seizures with or without secondary generalization, although a few patients may have primary generalized seizures."⁷ Other manifestations may also occur such as obstructive hydrocephalus from intraventricular cysts, arachanoiditis, focal and generalized encephalitis, altered mental status including psychosis, and vasculitis.^3,6,12,15 The nature of the clinical response of the host is dependent upon the location of the cysticerci as well as the numbers of cysts. However, postmortem studies have shown that 80% of cysticercus infestations are asymptomatic.⁸

Diagnosis is difficult because the clinical picture is frequently unremarkable. Neurological examination and EEG's are often normal or non-specific, and the clinical history may mimic other diseases.¹¹ Serologic testing while highly specific has a high number of false negatives. For example, an ELISA test is known to cross react with other helminthic infections.³ The most recently available test is the electroimmuno-transfer blot (EITB) assay. The EITB assay is reported to be 100% specific and "nearly 100% sensitive for patients with either multiple active parenchymal cysts or extraparenchymal neurocysticercosis." "However, the sensitivity is lower for patients with either single parenchymal cysts or calcifications alone."^3,7,8,15 In fact, in patients with only a single cysticercus lesion, the EITB showed only 4065% sensitivity.^6,15 "Conversely it is common to encounter asymptomatic EITB seropositive individuals in community studies."^1,13 Carpio reported that "only 18% of family members with a positive EITB test had parenchymal lesions on subsequent CT scan."³ Studies of the cerebral spinal fluid are also variable and may range from normal to showing pleomorphic cells and low glucose with elevated gamma globulin fraction.¹² But the EITB assay seems to show a high level of accuracy on spinal fluid.^5,8

The most accurate means of diagnosis, short of surgical biopsy, are with neuroradiologic methods involving both CT and MR scans. Both scanning methods show hydrocephalus when present. Both methods will also show living cysticerci as hypodense lesions that do not enhance with contrast, and within which a scolex may occasionally be seen. The CT scan is more sensitive if a cyst is in the calcified stage. In contrast, the MR is more effective in diagnosing the subarachnoid or intraventricular encysted larvae during the colloid and nodular-granular stages of pericyst inflammation and degeneration. During the colloid and nodular-granular stages, a CT scan with contrast shows annular or ring enhancement as a halo effect, which is felt to be due to perilesional edema.^{3,4,6,7,8,10,15}

Del Brutto attempted to establish the diagnostic criteria for cysticerci infestation to maximize the clin-ician's ability to accurately and effectively diagnose this elusive organism.⁵ These criteria include the visualization of a scolex or lesions suggestive of cysticercosis on neuroradiography, direct observation of the parasite on fundoscopy or histological methods, or positive immunologic testing for antibodies.

The treatment of parenchymal cysticercosis remains controversial, primarily due to a lack of adequate controlled studies. There are effective antihelminthics such as albendazole and praziquantel. However, it is unknown whether these medications improve the clinical course or, as some researchers noted, exacerbate the neurological compromise.^3,9

In contrast, surgical intervention and shunting to prevent the development of hydrocephalus is clearly indicated in ventricular or arachnoid space cysticercosis. Surgery is also commonly performed as a diagnostic procedure when the possibility of cysticercosis is not initially entertained, and the cysterical lesion is felt to be due to a glioma.^2,11

In 1999, Salinas et al reviewed the literature on the medical treatment of parenchymal cysticercosis with anti-helminthics. He found only four small trials with a total of 359 subjects of which 21% were lost to follow-up. In all cases the diagnosis was made radiologically and the cases were evaluated comparing placebo and treatment groups. Two of these studies merely dealt with radiologic improvement, but did not report clinical outcome. The other two studies showed no difference in seizure activity between the two groups, but one study did show an increase in the development of hydrocephalus in the post treatment group for.Also, only one of the studies treated the patients with steroids to prevent post treatment edema at the site of the encysted cysticercus larva.⁹

Conclusion

When alive, the cysticercus is immunologically inert and causes minimal damage and inflammation within the parenchyma of the brain. It is only when the encysted larva begins to die in the colloid/vesicular stage that the immune response and subsequent inflammation begins, leading to neurological complications. Given this pathophysiological sequence, several papers call into question the need to treat a parasite that is already dead or dying. Similarly, there seems to be minimal attendant neurological sequelae associated with the parenchymal nodular calcified stage.^3,11,15

Salinas et al were unable to draw any conclusions regarding the effectiveness of treatment with antihelminthics and left the recommendation for treatment open.⁹ Other authors felt that medical treatment may reduce future convulsive episodes.^2,5,10 Some believed that medical treatment has no effect at all or may even worsen the clinical course.^6,7,8,15 However, all papers agree that anti-convulsant medications should be used to treat seizures.

Cysticercosis will be more common in the industrialized countries with the increased influx of immigrants from underdeveloped and rural countries. Although protean in its neurological presentation, cysticercosis should be considered in the evaluation of any new seizure disorders or primary neurologic disturbances.

REFERENCES

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