Neurocysticercosis Update

Cysticercosis, most common parasitic disease of the central nervous system (CNS), affecting thousands of people in developing countries, is transmitted by fecal-oral contact by ingesting eggs of the porcine tapeworm, Taenia solium, by heteroinfection from a contact harboring the adult tapeworm or by autoinfection. The prevalence of neurocysticercosis (NC) in some developing countries exceeds 10%, where it accounts for up to 50% of cases of late onset epilepsy. In the past decade NC has been diagnosed with increasing frequency in industrialized nations. Several cases of NC have been reported in the US in both large metropolitan centers and less urban areas, in persons who lacked apparent risk factors for the disease. Factors contributing to the increased diagnosis of NC include increased immigration from endemic areas, travel to and from such regions throughout the world and improved diagnostics. ^{1, 2}

NC can be either active or inactive. Active NC is characterized by viable or degenerating cysticerci on imaging studies. Inactive lesions represent scars at sites of prior active infection, characterized by calcified foci. Clinical manifestations of NC are varied and nonspecific, related to the number, age and location of the cysts and the accompanying host immune response. The most common manifestations of NC are seizures, headaches, behavioral disturbances and signs and symptoms of increased intracranial pressure. Children most commonly have a solitary parenchymal lesion and present with an afebrile focal or generalized seizure. Cysticercotic encephalitis is a severe form of NC seen occasionally in children with large numbers of inflamed cysticerci. These patients show signs of acute encephalitis and diffuse brain edema. Signs of increased intracranial pressure are seen in patients with obstructive hydrocephalus caused by active or inactive ventricular cysts. Degeneration of cysts may be associated with a strong host inflammatory response in the brain tissue, which can produce signs and symptoms of encephalitis. ^{3, 4}

Diagnosis

The diagnosis of NC may be made by neural biopsy; however, alternative means are usually used for diagnosis. An accurate diagnosis of NC requires interpretation of clinical and epidemiologic data plus neuroimaging studies and results of specific serologic tests. A recent consensus statement proposed diagnostic criteria for NC based on objective clinical, imaging, immunologic and epidemiologic data. ⁵ Criteria for diagnosis of NC include 4 categories of criteria stratified on the basis of their diagnostic strength (Table 1), including: (1) absolute, histologic demonstration of the parasite from biopsy of a brain or spinal cord lesion, or cystic lesions showing the scolex on computerized tomography (CT) or magnetic resonance imaging (MRI), or direct visualization of subretinal parasites by funduscopic examination; (2) major, lesions highly suggestive of NC on neuroimaging studies, or positive serum enzyme-linked immunoelectrotransfer blot (EITB) for detection of anticysticercal antibodies, or resolution of intracranial cystic lesions after therapy with albendazole or praziquantel or spontaneous resolution of small single enhancing lesions; (3) minor, lesions compatible with NC on neuroimaging studies, or clinical manifestations suggestive of NC, or positive cerebrospinal fluid (CSF) enzyme-linked immunosorbent assay for detection of anticysticercal antibodies or cysticercal antigens or cysticercosis outside the CNS; and (4) epidemiologic, evidence of a household contact with T. solium infection, or individuals coming from or living in an area where cysticercosis is endemic or frequent travel to disease-endemic areas. Interpretation of these criteria permits two degrees of certainty: definitive diagnosis, or probable diagnosis (see Table 1). ⁵

TABLE 1: Diagnostic criteria for neurocysticercosis

CT and MRI findings in parenchymal NC depend on the stage of involution of cysticerci. Viable cysticerci appear as rounded cystic lesions on CT, without associated enhancement; degenerating parasites appear as focal enhancing lesions surrounded by edema; calcifications as hyperdense dots or nodules. MRI scans of cysticerci can be divided into a series of stages. Cystic hypointense lesions (density similar to CSF) without surrounding edema or enhancement correspond to viable cysts. Cystic lesions with surrounding edema or enhancement correspond to early degenerating cysticerci. Disappearance of the cyst fluid signals the degenerative phase and calcified nodules the residual phase. CT and MRI findings in subarachnoid NC include hydrocephalus, abnormal enhancement of the leptomeninges at the base of the skull or subarachnoid cysts. Ventricular cysticerci appear on neuroimaging studies as cystic lesions that distort the anatomy of the ventricular system and cause asymmetric hydrocephalus. MRI is better than CT for diagnosis of NC, particularly in patients with lesions at the base of the brain, brain stem cysts, intraventricular cysts and spinal lesions. However, MRI is less sensitive for detection of small calcifications. ^{6, 7}

Most serologic assays have limited value because of poor sensitivity and specificity. EITB has been determined to be the serologic test of choice, with specificity approaching 100% and sensitivity approaching 94%. Limitations of this diagnostic method include markedly decreased sensitivity in patients with single parenchymal lesions or calcifications. Additionally false positives can occur with extraneural cysts and/or exposure without active infection. The EITB method of diagnosis is more sensitive for testing serum than CSF despite the presence of CNS lesions. ^8–10

Treatment

The recommended treatment regimen for patients with NC is individualized, based on the viability, size and location of cysts; the severity of host immune response; and the presence or absence of complications such as hydrocephalus. The therapeutic approach to most patients with NC includes symptomatic drugs and specific an-tiparasitic agents. Surgical proce-dures are indicated in those with hydrocephalus from subarachnoid or ventricular cysts that require ventriculoperitoneal shunting.

Management of patients with nonviable cysts should be symptomatic and include anticonvulsants for patients with seizures. There is no consensus regarding the role of antiparasitic drugs for patients with active parenchymal cysts. Although some studies demonstrate more rapid resolution of radiographic abnormalities with antiparasitic therapy, it is unclear whether this is associated with improved neurologic outcome. ¹¹ Some studies have shown a decreased risk of developing chronic seizures in patients treated with cysticidal drugs. ¹² The adjunctive use of antiparasitic and corticosteroid therapy may improve neurologic outcome and decrease the rate of shunt failure. Patients with severe cysticercotic encephalitis should not receive antiparasitic drugs because this may exacerbate intracranial hypertension. ^11–14

Praziquantel (50–100 mg/kg/day for 15 or more days) and albendazole (15 mg/kg/day with a maximum of 800 mg given for 8 or more days) are effective against cysticerci. Albendazole is the drug of choice because: it is less expensive than praziquantel; it has 20% more cysticidal activity than praziquantel; when administered jointly with dexamethasone, plasma levels of albendazole increase but levels decrease with praziquantel; and it has minimal toxicity. Neither drug has been proved consistently better than placebo in controlled trials. ¹⁵

Between the second and fifth day of antiparasitic therapy, there is often an exacerbation of neurologic symptoms attributed to local inflammation in response to the death of the larvae. Consequently antiparasitic drugs are given in conjunction with steroids to minimize intracranial hypertension. Corticosteroids are indicated for all patients with multiple cysts and associated cerebral edema. ¹⁵