Cysticercosis is an increasingly common medical problem in the United States, especially in the Southwest and other areas where large populations migrated from endemic areas and among populations that often travel to these areas.
Cysticercosis is a tissue infection with the cysticercus, or larval, stage of Taenia solium (pork tapeworm) that results from ingestion of T solium eggs. The clinical syndromes caused by T solium are categorized as either cysticercosis (cysts in various tissues including the brain) or taeniasis (intestinal tapeworm infection).
Cysticercosis can involve skeletal muscles, subcutaneous tissues, eyes, the central nervous system (CNS), and other tissues. Neurocysticercosis refers to CNS infection with T solium. Neurocysticercosis, which is probably the most common parasitic infestation of the CNS, has gained increased recognition in the last two decades because of the development of MRI and CT scanning in the United States and in countries where neuro cysticercosis is endemic.
Neurocysticercosis is further divided into parenchymal and extraparenchymal disease. Parenchymal disease is characterized by infection with cysticerci within the brain parenchyma. Extraparenchymal disease develops when cysticerci migrate to the CSF of the ventricles, cisterns, and subarachnoid space or within the eyes or spinal cord.
When humans ingest undercooked pork that contains cysticerci of T solium, the scolex evaginates from the cyst and develops into an intestinal tapeworm (taeniasis). The tapeworm grows to a length of up to 10 meters and has hundreds of proglottids. Mature proglottids contain approximately 50,000 eggs each. Free eggs or whole proglottids are released periodically into the stool of the carrier and can survive in the environment for many months.
When pigs ingest the proglottids or eggs, the eggs hatch, penetrate the pigs' intestinal wall, and spread to skeletal muscle, especially the neck, tongue, and trunk. There, the larvae mature into encysted cysticerci over 2-3 months. The cysticerci suppress the host inflammatory response and can survive in tissues for months to years. The life cycle is completed when humans ingest inadequately cooked pork that contains viable cysticerci.
This cycle of cysts in pigs and tapeworms in humans can be broken if a human ingests eggs excreted in the feces of a human carrier of the pork tapeworm. Humans are an accidental host of the larval stage and develop cysticercosis similar to that in pigs. These cysticerci have tropism for neural tissue and migrate to the brain, although they can also be found in skeletal muscle. Thus, cysticercosis is a foodborne infection and can be acquired in the absence of pork consumption.[1]
Humans can be infected with eggs through fecal-oral transmission or possibly through autoinfection. Fecal-oral contamination usually occurs via infected food handlers via ingestion of fruit and vegetables fertilized with contaminated human waste. The eggs are sticky and can often be found under the fingers of tapeworm carriers. Thus, even populations who do not eat pork can develop cysticercosis. The egg-containing feces can contaminate water supplies in endemic areas. If the water is used to irrigate fruits and vegetables, eggs are ingested with the contaminated food. Thus, people who have never visited endemic countries can also develop infection.
Cysticerci are able to survive in the human brain by disarming host defenses. The cysticercus secretes prostaglandins and other compounds (paramyosin, taeniastatin, sulfated polysaccharides) that inhibit or divert complement activation and cytokine production, resulting in only minimal host inflammation around the viable cysticercus. In addition, humoral antibodies do not kill the mature metacestode. Taeniastatin and other poorly defined factors may also interfere with lymphocyte proliferation and macrophage function, inhibiting normal cellular immune defenses. The clinical manifestations commonly result when an inflammatory response develops around a degenerating cysticercus after it has died.
Over a period of years, the parasite may lose its ability to control the host defenses. Consequently, an inflammatory response leads to degeneration of the cysticercus. An inflammatory response that occurs in the CNS parenchyma causes seizures typical of parenchymal neurocysticercosis. As the degeneration continues, the parasite becomes encased in a granuloma, which either resolves or leads to scarring and calcification. In rare cases, patients with numerous parenchymal cysticerci develop a diffuse cerebral edema termed cysticercal encephalitis. Pathologically, cysticercal encephalitis may progress to meningoencephalitis, granulomatous meningitis, focal granulomas or abscess, hydrocephalus, ependymitis, or arteritis.
Approximately 10-20% of patients with neurocysticercosis present with extraparenchymal disease, often with concomitant parenchymal disease. Subarachnoid neurocysticercosis may form in the gyri of the cerebral convexities or in the fissures of the brain, especially the sylvian fissures. These forms of neurocysticercosis are associated with parenchymal inflammation and resemble parenchymal disease in manifestations and pathogenesis.
In severe cases, cysticerci in the sylvian fissures may enlarge to several centimeters in diameter and cause mass effects. Cysticerci can form in the ventricles of the brain, where they can cause hydrocephalus by blocking the outflow of CSF. Obstructive hydrocephalus may also be caused by associated ependymitis. If cysticerci form in the basal cisterns, they can cause basilar arachnoiditis. Arachnoiditis may result in communicating hydrocephalus or vasculitis. Involvement of the arteries may lead to lacunar infarctions or, occasionally, large-vessel strokes.
Cysticerci may be located in the spinal subarachnoid space and the spinal cord medulla. Medullary cysticerci may cause cord compression or other symptoms related to their location. Ocular cysticercosis is generally intravitreal or subretinal. Skeletal muscle cysticerci are common but usually cause only minor local symptoms unless they are present in overwhelming numbers. Subcutaneous cysticerci manifest as painless, palpable, cystic lesions. CNS parenchymal cysticerci may be present in patients with suspected extraparenchymal or extra-CNS disease.
Approximately 2,000 patients are hospitalized for neurocysticercosis each year in the United States.[2] Most occur among Latin American immigrants in locations such as California, Arizona, and Texas. Less frequently, cysticercosis is observed in immigrants from other areas, including India, Asia, and Africa. A small number of cases of cysticercosis develop in people born in the United States who have traveled to areas in which the infection is endemic. These travelers are often the children of immigrants. Locally acquired infection is rare and is associated with contact with a tapeworm carrier. All tapeworm carriers acquire infection from areas of endemic disease.
In a mortality study using data from the National Center for Health Statistics from 1990 to 2002; 62% of patients with cysticercosis had emigrated from Mexico.[3]
International
An estimated 50-100 million people are infected with cysticercosis worldwide. This is probably an underestimate since many infections go undiagnosed. The World Health Organization (WHO) estimates suggest 2.56-8.30 million cases of neurocysticercosis globally.[2] Neurocysticercosis is one of the leading causes of adult-onset seizures worldwide. CT scanning and MRI of the brain have greatly improved the diagnosis of neurocysticercosis.
Areas of endemic disease include Central and South America, India, China, Southeast Asia, and sub-Saharan Africa.[4] Studies in Latin America and India have noted adult-onset seizures in approximately 2% of the population, with as many as half due to neurocysticercosis. In Latin America, the seroprevalence rate ranges from 4.9-24%. In India, the estimated prevalence is similar. Rural China and Korea have lower infection rates. The seroprevalence in certain rural South American communities is as high as 10-25%.[5] The estimated true prevalence of human taeniasis and cysticercosis in rural Vietnam is as high as 13% for each.[6] There is also an indication that cysticercosis and taeniasis are present across eastern European countries.[7]
Mortality/Morbidity
Neurocysticercosis is the most frequent preventable cause of epilepsy worldwide and is estimated to cause 30% of all epilepsy cases in endemic countries. In 2015, the WHO’s Foodborne Disease Burden Epidemiology Reference Group identified T solium as a leading cause of death from foodborne diseases, resulting in a considerable total of 2.8 million disability-adjusted life-years. Neurocysticercosis was found to be responsible for 10% of newly onset seizures in one Los Angeles, California, emergency department.[8] Overall, among patients who presented to emergency departments with newly onset seizure, neurocysticercosis was found to be responsible for 2.1-5.7% of cases.[9]
A total of 221 deaths were attributed to cysticercosis in the United States from 1990-2002.[3]
Although some patients die of status epilepticus in areas with poor access to medical care, mortality due to parenchymal disease is rare. With modern medical and surgical care, mortality due to extraparenchymal disease is also unusual. However, without aggressive surgical management, hydrocephalus is potentially life-threatening. Even with shunting procedures, subarachnoid cysticercosis is associated with a high 10-year fatality rate.
Race
Immigrants from countries where T solium is endemic are more likely to be infected. While most of these immigrants are Hispanic and some are Asian, prevalence rates appear to be related more to exposure than to genetic predisposition.
Nearly 75% of all hospitalized patients in the United States with neurocysticercosis were Hispanic.[10]
Sex
Cysticercal encephalitis, a severe form of cysticercosis, is more common in children and young females. The cause is unknown.
US hospitalizations were more common among males.[10]
No other sex predisposition has been noted.
Age
Patients with cysticercosis are typically aged 10-40 years. However, cases have been described in every age group.
People aged 20-44 years were at an increased risk for hospitalizations in the United States.[10]
Most patients with parenchymal cysticercosis either remain asymptomatic or develop a self-limited seizure disorder.
Among patients who develop intracerebral calcifications, most have recurrent seizures unless treated with anticonvulsants. If treated with anticonvulsants, the seizures are generally easily controlled.
Ventricular neurocysticercosis usually requires shunting. Neurosurgery may be complicated by focal neurologic damage. Shunt revisions are often needed unless patients are treated with corticosteroids or antiparasitic drugs. However, even with treatment, some still require subsequent revision. Prior to the use of corticosteroids and antiparasitic drugs, subarachnoid disease was associated with a 90% 10-year fatality rate, even with shunting. With current management, fatalities appear to be rare.
Good evidence indicates that, once infected, patients are immune to reinfection.
Patients and their family members should be educated on how to decrease the source of egg carriers by emphasizing improvement in sanitation, separation of pigs from humans, and food-preparation hygiene in endemic areas.
Family members should also be screened and queried about symptoms suggestive of tapeworm infection, such as passing proglottids. They should be treated if symptoms are present.
Family members should also be screened.
Patients with seizures and their families should know proper seizure first-aid.
Patients who have had seizures should know about possible driving restrictions, which, in the United States, vary from state to state.
Patients who have received a VP shunt should be educated about the signs and symptoms of elevated ICP (possible shunt failure) and meningitis (secondary infection of indwelling hardware).
For excellent patient education resources, please see eMedicineHealth's Infections Center.
Postmortem studies in endemic areas suggest that 80% of neurocysticercal infections are asymptomatic.[11] Consequently, many cases are never diagnosed or are found incidentally during imaging procedures.
The peak severity of neurocysticercosis has been estimated to occur 3-5 years after initial infection, but it can be delayed for more than 30 years. After a variable period of degeneration, cysts can become calcified and may then become inactive. Once they are calcified, they may cease to cause symptoms or may serve as a focus for epileptic activity. The symptoms of neurocysticercosis depend on the stage, site, and number of cysticerci. Cysts frequently develop in multiple locations, and a combination of active and inactive cysts in the same patient is not uncommon.
Symptoms of cysticercosis may include seizures, elevated intracranial pressure (ICP), meningoencephalitis, psychiatric disorder, stroke, and/or radiculopathy or myelopathy, if the spinal cord is involved.
The symptoms are mainly due to mass effect, an inflammatory response, or obstruction of the foramina and ventricular system of the brain. The most common symptoms include seizures, focal neurologic signs, and intracranial hypertension.
Generally, the patient’s history includes exposure to an area where the parasite is endemic and an adolescent- or adult-onset seizure disorder. Symptoms of hydrocephalus should raise concerns about extraparenchymal disease.[12]
Parenchymal CNS disease
Seizures may be focal, focal with secondary generalization, or generalized.
Headaches are common and may be migrainelike or tension-type.
Neurocognitive deficits, while rare, may include learning disabilities, depression, or even psychosis[13] .
Extraparenchymal disease
Most patients present with headaches or symptoms of hydrocephalus.
Symptoms of increased ICP may include headache, nausea or vomiting, altered mental status, dizziness, and decreased visual acuity due to papilledema.
Patients with numerous cysticerci in the basilar cisterns may present with communicating hydrocephalus, meningismus (without fever), symptoms of lacunar infarcts due to small-vessel vasculitis, or symptoms of large-vessel infarcts due to cysticercal erosion into major arteries or severe inflammation of those arteries.
Patients with spinal cysticerci typically present with radicular symptoms, but rarely with motor or sensory deficits traceable to a spinal level.
Patients with ocular cysticerci report visual changes.
Meningoencephalitis may manifest as pyrexia, altered senses, seizures, increased ICP, multiple cranial nerve involvement, or even brainstem or cerebellar involvement.
Both parenchymal and extraparenchymal disease can cause elevated ICP. Signs include hyperreflexia, papilledema (a late sign), and the Cushing reflex (a preterminal event).
Parenchymal disease
Physical examination findings are usually normal.
Patients who have had seizures may have typical manifestations of the postictal state, with somnolence, an altered level of consciousness, and poor memory.
Focal neurologic deficits are unusual and suggest alternative diagnoses, such as tuberculoma, tumor, or, rarely, extraparenchymal neurocysticercosis.
Extraparenchymal disease
Ocular cysticerci are visible upon ophthalmologic examination.
Rare spinal cysticerci manifest as sensory or motor deficits or back tenderness.
Patients with neurocysticercosis of the cisterns may present with lacunar infarcts or large-vessel infarction with associated upper motor neuron signs.
Approximately half of all cysticercosis cases have cutaneous manifestations, which can present as subcutaneous swellings.[14]
Subcutaneous cysts may be palpable as fluid-filled nodules that resemble sebaceous cysts.
Extraneural cysticercosis: Extraneural infection with T solium typically involves the eye, muscle, or subcutaneous tissue. It is not known whether oncospheres actively migrate to those organs or passively enter tissues during high blood flow.
Neurocysticercosis: Infection of the CNS with T solium cysticercus and associated host inflammation.
Parenchymal disease causes seizures but few long-term complications. However, studies suggest that childhood infection may be associated with learning disabilities and cognitive dysfunction.
Extraparenchymal disease may cause elevated ICP, resulting in herniation and death.
Vasculitis associated with cisternal neurocysticercosis may cause strokes, communicating hydrocephalus, and death.
The diagnosis of cysticercosis is often based on clinical presentation, abnormal findings on neuroimaging, and serology. Occasionally, more invasive procedures (eg, brain biopsy) are required.[15]
Del Brutto et al have previously defined and modified the diagnostic criteria for definitive and probable neurocysticercosis in 2001 and 2012, respectively. These criteria were revised in 2017.[16]
Absolute criteria
Absolute criteria include the following:
Histological demonstration of the parasite on biopsy from the brain or spinal cord lesion
Visualization of subretinal cysticercus
Conclusive demonstration of a scolex within a cystic lesion on neuroimaging studies
Neuroimaging criteria
Major neuroimaging criteria include the following:
Cystic lesions without a discernable scolex
Enhancing lesions
Confirmative neuroimaging criteria include the following:
Resolution of cystic lesions after cysticidal drug therapy
Spontaneous resolution of single small enhancing lesions
Migration of ventricular cysts documented on sequential neuroimaging studies
Minor neuroimaging criteria: Obstructive hydrocephalus (symmetric or asymmetric) or abnormal enhancement of basal leptomeninges
Clinical/exposure criteria
Major clinical/exposure criteria include the following:
Detection of specific anticysticercal antibodies or cysticercal antigens via well-standardized immunodiagnostic tests
Cysticercosis outside the CNS
Evidence of household contact with T solium infection
Minor clinical/exposure criteria include the following:
Clinical manifestations suggestive of neurocysticercosis
The patient came from or lives in an area where cysticercosis is endemic
Degrees of diagnostic certainty
Definitive diagnosis requires one of the following:
One absolute criterion
Two major neuroimaging criteria plus any clinical/exposure criterion
One major and one confirmative neuroimaging criteria plus any clinical/exposure criterion
One major neuroimaging criterion plus two clinical/exposure criteria (including at least one major clinical/exposure criterion), together with the exclusion of other pathologies that produce similar findings
Probable diagnosis is supported by one of the following:
One major neuroimaging criteria plus any two clinical/ exposure criteria.
One minor neuroimaging criteria plus at least one major clinical/ exposure criteria.
Findings from laboratory studies such as routine CBC counts and liver function tests are not specific. The WBC count is usually within the reference range, and most patients do not have eosinophilia unless a cyst is leaking, in which case the eosinophilia may be pronounced.
Serologic studies can be helpful in the diagnosis of cysticercosis but are limited in their usefulness in a community setting by general lack of availability, as follows:
An enzyme-linked immunoblot transfer blot (EITB) assay can demonstrate serum or CSF anticysticercal antibodies. The findings in the serum are more sensitive than those in the CSF. The assay is highly specific for exposure to T solium. The sensitivity is high (94%) in patients with multiple lesions or extraparenchymal infection but may be as low as 28% in patients with a single parenchymal lesion. EITB assay findings may revert to negative after the cysticercus dies and are often negative in patients with only calcified lesions.
ELISAs that use unfractionated antigen are fraught with problems regarding sensitivity and specificity, and they are reliably diagnostic only when performed on CSF.
The observed cross-reactivity of infected sera with antigens of other parasites has limited the accuracy of serologic techniques such as ELISA. The western blot kit (QualiCode) offers qualitative detection of immunoglobulin G (IgG) antibodies to T solium with a sensitivity of 95% and a specificity of 100%. It yields rapid results (< 90 min).
The sensitivity of ELISA using CSF is approximately 80%. False positive results may occur in patients with hydatid cysts, filariasis, tuberculous meningitis, or viral encephalitis. An active inflammatory response is likely to cause high titers; intraventricular cysts cause a low titer.
An assay using monoclonal antibody HP10 to detect parasite secretory/excretory antigens performed well in CSF samples, with results similar to those from the EITB assay.[17]
A 2017 meta-analysis found that ELISA for antibodies and EITB yield a similar diagnostic value.[18]
No polymerase chain reaction (PCR) tests are available.
Carriage of tapeworms in humans can be diagnosed via detection of proglottids or eggs in feces, Taenia antigens in stool, or specific antibodies in serum.[19]
Stool examination for ova and parasites can occasionally be used to diagnose intestinal infection with T solium. However, most people diagnosed with cysticercosis do not have viable T solium tapeworm in their intestine, so eggs are not typically found.
Because eggs are shed intermittently, most cases of taeniasis cannot be detected with a single stool test.
Furthermore, egg morphology is the same for T solium and Taenia saginata.
Antigen detection tests for stool and serologic tests for tapeworms are being studied; none is available for use in clinical practice.
Identifying tapeworm carriers does not usually help in diagnosing neurocysticercosis, but it may be useful in detecting the source of infection in cases among US residents who have not traveled.
Neuroimaging with contrast-enhanced CT scanning or MRI is the mainstay of diagnosis.
MRI is better for detecting intraventricular types and extraparenchymal disease and visualizing the scolex within the cysticercus (as high intensity inside a cyst). Fluid attenuation inversion recovery (FLAIR) sequences are particularly helpful for identifying associated edema and the scolex.[20]
CT scanning is better for detecting intracerebral calcifications.
Both modalities can reveal hydrocephalus and active intraparenchymal lesions.
The ventricles may be narrowed with extensive low attenuated areas in the parenchyma, sparing the cortex.
A ring enhancing active lesion with surrounding edema is the second-most-common finding.
A homogenously enhancing lesion represents a dying larva.
Calcified lesions are also common on CT scans.
View Image
Nonenhanced CT scan of the brain demonstrates the multiple calcified lesions of inactive parenchymal neurocysticercosis.
Neurocysticercosis is classified as parenchymal or extraparenchymal based on the location of the parasite and surrounding host tissue on neuroimaging.[20]
Parenchymal form
The viable parenchymal form is characterized by vesicular lesions, often with evidence of associated contrast enhancement and/or surrounding edema. The scolex is often visible on high-definition imaging. This represents parasites with an intact cyst wall, vesicular fluid, and scolex, with variable degrees of inflammation surrounding the parasite, sometimes invading the cyst wall.
A single small enhancing cystic or nodular enhancing lesion smaller than 2 cm represents parasites in the process of degeneration with surrounding inflammation and variable cyst fluid.
Nodular calcifications smaller than 20 mm in diameter with or without surrounding edema and/or contrast enhancement are seen in nonviable form, representing calcified granuloma with or without surrounding inflammation and/or gliosis.
Extraparenchymal form
Intraventricular cysticerci can be seen within the ventricles and may cause obstructive hydrocephalus or loculated hydrocephalus with disproportionate dilation of the ventricles on CT/MRI.
Subarachnoid cysticerci are found in the sylvian fissure, basilar cisterns, or interhemispheric spaces. These can present as stroke or meningitis without discrete cysts. The cysticerci often appear in clusters with proliferating membranes (racemose) and may lack a scolex.
Spinal cysticerci are seen within the spinal subarachnoid space with or without evidence of inflammation/diffuse spinal arachnoiditis. Intramedullary cysticerci can also be within the spinal cord.
EEGs are frequently obtained in patients who have experienced seizures. The EEG is abnormal in up to 50% of cases, demonstrating various findings (diffuse slowing, focal paroxysmal activity, generalized spike waves) depending on lesion number, size, and location.
No pattern is diagnostic for neurocysticercosis.
Focal abnormalities may be present in persons with active disease.
Seizures may also be caused by inactive disease (calcified nodules of the residual phase), but, in these cases, the EEG does not usually reveal focal abnormalities.
In patients who will likely require prolonged corticosteroid therapy, screening for latent tuberculosis and Strongyloides stercoralis infection is suggested before therapy is initiated.[20]
Lumbar puncture: Lumber puncture for a CSF study is usually unnecessary in the diagnosis of neurocysticercosis. This procedure is also contraindicated upon suspicion of increased ICP. If a lumber puncture is performed, examination of CSF shows a normal glucose concentration and protein levels and WBC counts that are usually only mildly elevated. CSF studies in individuals who have a leaking cyst that communicates with the CSF may reveal prominent CSF eosinophilia.
Biopsy: Biopsy may be required in patients with suspected neurocysticercosis who have a single brain lesion with no characteristic scolex and negative serology findings. Biopsy specimens may be taken from subcutaneous nodules or a muscle lesion. Biopsy of CNS lesions is rarely necessary.
Occasionally, CNS lesions are mistakenly identified as tumors and are diagnosed only at surgery. Upon gross examination, the cysticerci appear as 5- to 10-mm semiopaque cysts with a 1- to 2-mm mural nodule containing the scolex.
Histopathologic examination reveals a superficial tegument layer covered with microtriches, a cellular layer below that containing the cell nuclei and musculature, and a loose reticular layer characterized by canaliculi. When the parasites are viable, little surrounding inflammation is observed. Degenerating parasites, on the other hand, are invaded with an inflammatory infiltrate including lymphocytes, macrophages, plasma cells, neutrophils, and eosinophils. Cavellani et al used autopsy protocols to study the influence of age and gender on cardiac and encephalic inflammation caused by cysticercosis. They concluded that inflammation decreases with age and depends on the stage of the disease; women have a more intense response during senescence.[21]
Histologic studies have shown that viable cysticerci in humans and pigs have little or no surrounding inflammation.[22]
Cysticerci can persist in the human host for long periods, often years, without eliciting a surrounding inflammatory reaction.
In contrast, the immune-mediated inflammation around one or more degenerating cysts may precipitate symptomatic disease.
When the parasite begins to involute, either naturally or after treatment with anticysticercal drugs, granulomatous inflammation develops around the cysticerci. The predominant components of this inflammatory response include plasma cells, lymphocytes, eosinophils, and macrophages. The latter engulf parasite remnants, eventually leaving a gliotic scar with calcifications.
Early granulomas in cysticercosis are predominantly associated with a Th1 response, whereas later granulomas, in which parasite destruction is complete, have a mixture of Th1 and interleukin-4 (IL-4). The Th1 response appears to play an important role both in the pathogenesis of disease and in the clearing of the parasites, with IL-4 involved in downregulation of the initial response.
Asymptomatic cysticercosis: As mentioned above, more than 80% of patients with cysticercosis are asymptomatic. No evidence has shown that administering antiparasitic therapy for asymptomatic nonviable cysticercal lesions found incidentally in the brain is beneficial.
Patients who are found to have cysticerci only in subcutaneous or intramuscular sites generally do not require specific therapy.
If a single extracranial lesion is found, excision can be considered after neurocysticercosis is excluded with brain imaging.
Patients with ocular cysticercosis who have extraocular muscle involvement may present with diplopia and recurrent eye pain. Treatment with albendazole and corticosteroids has proven to be beneficial. Some patients may require surgical excision. For intraocular cysticerci, surgical removal is preferred over antiparasitic drug therapy.[20]
Patients with subcutaneous or intramuscular cysticercosis who develop symptoms due to inflammation can be treated with cysticerci excision or anti-inflammatory agents. Excision is the treatment of choice for a solitary symptomatic lesion.
Symptomatic therapy for neurocysticercosis should be the focus of initial and emergency management, as follows:
Antiepileptic drug therapy in patients presenting with seizures
Anti-inflammatory drugs such as corticosteroids and methotrexate in patients with cerebral edema or vasculitis
Shunt surgery for hydrocephalus
Antiparasitic treatment is important but should never be considered emergently. Antiparasitic drugs can worsen cerebral edema and should be avoided in patients with increased intracranial pressure due to either diffuse cerebral edema or untreated hydrocephalus.[23]
Parenchymal cystic neurocysticercosis has better outcomes if treated with antiparasitic drugs along with corticosteroids. Treatment recommendations for parenchymal neurocysticercosis depend on its form, as follows:[20]
In patients with untreated hydrocephalus or diffuse cerebral edema, management of elevated intracranial pressure alone is recommended.
For viable parenchymal cysticercosis, antiparasitic drugs should be administered unless the intracranial pressure is increased. For 1-2 viable parenchymal cysts or a single enhancing lesion, monotherapy with albendazole is recommended. The usual dose is 15 mg/kg/day in 2 daily doses (up to 1200 mg/day) with food for 10-14 days.
For more than two viable parenchymal cysts, a combination of albendazole (15 mg/kg/day in 2 daily doses up to 1200 mg/day) and praziquantel (15 mg/kg/day in 3 daily doses) for 10-14 days is recommended.
Corticosteroids should be given whenever antiparasitic drugs are used.
Antiepileptic drugs should be administered to all patients with seizures.
Antiparasitic treatment is not recommended for calcified parenchymal neurocysticercosis.
Ventricular neurocysticercosis of the third and lateral ventricles should be treated with minimally invasive surgery, when possible. Adherent cysticerci should be managed with CSF diversion along with antiparasitic drugs. Minimally invasive and open craniotomies are options for fourth-ventricular disease. Antiparasitic drugs should be deferred until after surgical therapy. Treatment recommendations for extraparenchymal neurocysticercosis are as follows:[20]
For intraventricular neurocysticercosis of the lateral and third ventricles, removal of the cysticerci via minimally invasive neuroendoscopy, when possible, is recommended over other surgical or medical approaches for cysticerci. Antiparasitic drugs should not be used preoperatively, since such treatment could result in disruption of parasite integrity, and an inflammatory response could prevent successful cyst removal.
When surgical removal of fourth-ventricular cysticerci is possible, this is recommended over medical therapy and/or shunt surgery.
When surgical removal is technically difficult, shunt surgery for hydrocephalus is suggested.
For intraventricular neurocysticercosis, corticosteroid therapy is recommended to decrease brain edema perioperatively. Antiparasitic drug therapy along with corticosteroid therapy is suggested following shunt insertion to decrease subsequent shunt failure in patients in whom surgical removal of isolated intraventricular cysts is not possible.
For subarachnoid cysts, antiparasitic drug therapy is recommended until radiologic resolution of viable cysticerci on MRI and resolution of other evidence of cysticerci.
Methotrexate is suggested as a steroid-sparing agent in patients who require prolonged anti-inflammatory therapy.
Shunt surgery in addition to medical therapy is recommended in patients with hydrocephalus due to subarachnoid neurocysticercosis. Some patients may benefit from surgical debulking over shunt surgery alone.
For spinal neurocysticercosis, corticosteroid treatment is recommended in patients with evidence of spinal cord dysfunction, along with antiparasitic therapy.
For intraocular cysticerci, surgical removal is preferred over antiparasitic drug therapy.
Consultation with a neurosurgeon is essential in patients with hydrocephalus, significant mass effect, or extraparenchymal CNS disease.
Consultation with a neurologist is needed if protracted or refractory seizures occur.
Consultation with an infectious disease specialist is recommended if active disease is suspected.
An ophthalmologist should be consulted for patients with ocular neurocysticercosis. At a minimum, a funduscopic examination should be performed before the initiation of antiparasitic drug therapy.
No activities are restricted if the patient is otherwise asymptomatic.
All patients who present with seizures should take seizure precautions. Patients with a history of seizures may have state-required restrictions on driving motor vehicles. Physicians may be responsible for informing patients about these restrictions.
Patients with hydrocephalus may have ataxia and may be at risk for falls.
Educate patients regarding routes of transmission of cysticerci ova.
Meat inspection has been effective at preventing transmission of tapeworms in developed countries but has been uniformly unsuccessful in developing countries. Thorough cooking of meat is a primary prevention measure. Freezing at -5°C for 4 days, -15°C for 3 days, or -24°C for one day kills the cysticerci.[24]
In areas of endemic cysticercosis, avoid undercooked pork to reduce the risk of intestinal infection.
Be vigilant about avoiding potential fecal-oral transmission to reduce the risk of neurocysticercosis while in endemic areas. Individuals traveling to such areas should observe the following guidelines:
Eat only fruits and vegetables that you have peeled yourself.
Thoroughly wash (with water from a clean source) all food prior to ingestion.
Maintain good personal hygiene and wash hands prior to food preparation.
A combination of mass treatment for tapeworm carriage, mass treatment of pigs, and vaccination of pigs shows potential for interrupting transmission of T solium infection in endemic regions, as demonstrated in Peru.[25]
Mass chemotherapy has been used to interrupt transmission in some areas of endemic infection, but disease usually returns within a few years.
Mass anthelminthic therapy yields only limited success and may cause adverse neurologic events in individuals with undiagnosed neurocysticercosis who receive these drugs.
Consider identifying human carriers of tapeworms, possibly based on a history of proglottid passage, and instituting targeted treatment.
Serologic screening of the contacts of patients should also be considered in the management of cysticercosis, particularly in nonendemic countries when transmission may have occurred within a household (eg, via food prepared by a household worker from an endemic country).
Vaccines for prevention of cysticercosis have proven effective for other Taenia species and are in development for T solium.
Transmission of cysticercal infections to pigs can be prevented with the following measures:
Changing pig-raising practices in endemic areas by confining the animals and preventing them from roaming freely to avoid contact with infectious ova excreted in human feces
Improving sanitary conditions and proper disposal of human stool
Possibly vaccinating pigs (Preliminary studies suggest this may be feasible.)
The initial brain reimaging should be performed two months after therapy completion.
MRI should be repeated at least every 6 months until resolution of the cystic component.[20]
Parasite antigen levels typically fall by 3 months after successful treatment.
If the cysts are growing in the absence of therapy, antiparasitic therapy should be considered.
In patients with seizures due to neurocysticercosis without calcification, perform imaging studies every 3-6 months. If calcification develops, lifelong anticonvulsant therapy is indicated, and further imaging studies can be performed as needed.
Tapering and discontinuation of antiepileptic therapy can be considered in patients with few seizures prior to antiparasitic therapy, resolution of cystic lesions on imaging studies, and no seizures for 24 consecutive months. In patients with a single enhancing lesion and no risk factors for recurrence, antiepileptic drugs can be discontinued after resolution of cystic lesions. Risk factors for recurrent seizures include the following:[20]
Calcifications on follow-up CT scanning
Breakthrough seizures
More than two seizures during the disease course
Patients with calcified lesions and a seizure disorder should be maintained on anticonvulsants indefinitely, and they should undergo imaging studies only as needed.
Monitor anticonvulsant serum levels to prevent toxicity.
ICU monitoring is necessary in patients with uncontrolled seizures, elevated ICP, or severe extraparenchymal disease.
If antiparasitic therapy is provided, patients should be hospitalized and monitored during the initial phase.
As cysticerci die, neurologic symptoms may worsen because of an increased inflammatory response.
Most symptoms associated with antiparasitic therapy develop within 3-5 days of beginning therapy.
Antiparasitic therapy may then be completed in an outpatient setting.
Prior initiation of therapy with antiparasitic medications or corticosteroids, the following steps should be taken:
Apply a purified protein derivative (PPD) skin test. Patients in whom the PPD result is positive should be treated with isoniazid along with pyridoxine (vitamin B6) for the duration of their steroid treatment.
Because many patients with cysticercosis also have risk factors for strongyloidiasis, these patients should be treated with ivermectin (200 μg/kg administered in two single doses two weeks apart before steroids are initiated.
An ophthalmologist should perform an eye examination to exclude ocular cysticercosis.
Patients with extraparenchymal neurocysticercosis should be treated at hospitals with active neurosurgical and neurological services because emergency procedures such as shunt placement or ventriculostomy may be required in patients with worsening hydrocephalus.
Arrange transfer if the facility is unable to provide neurologic or neurosurgical care.
Anticonvulsant and anti-inflammatory (steroid) medications are the basis of medical therapy in symptomatic patients. Antiparasitic drugs have not been shown to provide a consistent long-term benefit in patients with parenchymal disease and seizures.
Clinical Context:
Widely available and inexpensive. Has significant drug interactions, and dosage should be adjusted based on therapeutic effect and serum levels. Fosphenytoin may be considered for IV administration if available because it is better tolerated than IV phenytoin, but it is considerably more expensive than phenytoin.
Clinical Context:
Use if phenytoin unavailable, ineffective, or contraindicated. Anticonvulsant therapy should be used for one year after resolution of the active parasitic infection followed by a trial of treatment discontinuation if the patient remains seizure-free.
Clinical Context:
Use if phenytoin unavailable, ineffective, or contraindicated. Interferes with transmission of impulses from thalamus to cortex of brain. Used as sedative.
Anticonvulsants should be used in patients with seizures or who are at high risk for recurrent seizures. Patients with parenchymal calcifications carry a high risk of seizure recurrence if anticonvulsants are tapered; therefore, these patients usually remain on anticonvulsants indefinitely. In contrast, patients with active cysticerci in whom lesions resolve without developing calcification should be treated with anticonvulsants until they are free from seizures for at least one year and results of neuroimaging studies show normalization. Anticonvulsants may then be tapered. Patients with recurrent seizures should be maintained on long-term anticonvulsant therapy.
A double-blind, placebo-controlled study in 2004 compared two groups of patients with viable parenchymal cysts, with seizures being treated with anticonvulsants, to see whether anticysticercal drugs improved seizure control. During 30 months of follow-up, the proportion of patients having partial seizures was similar for the group who took albendazole and dexamethasone and those who took placebos, but the treatment group had significantly fewer seizures with generalization, and more of their intracranial lesions resolved. Except for abdominal pain, adverse effects did not differ significantly.[26]
Phenytoin, carbamazepine, and phenobarbital induce metabolism of praziquantel.
Clinical Context:
Use in patients with cysticercal encephalitis or in patients with severe mass effect, edema, or vasculitis if preferred over prednisone.
These agents should be used immediately in patients with significant cerebral edema, mass effect, or vasculitis associated with neurocysticercosis. High doses (approximately 1 mg/kg/d of prednisone) should be used. High-dose dexamethasone (30 mg/d) should be used initially to treat cysticercal encephalitis. If cerebral edema resolves, patients may be treated with antiparasitic drugs later. Long-term courses of corticosteroids should be used in patients with subarachnoid neurocysticercosis who have meningitis, stroke, or communicating hydrocephalus and should be tapered as soon as possible based on lumbar puncture and neuroimaging results.
Long-term course of corticosteroids may also prevent shunt failure in patients with VP shunt and active disease. Patients with intramedullary spinal neurocysticercosis should be treated with steroids until resolution of cord edema. Patients receiving long-term corticosteroids should be given calcium supplementation to help counterbalance osteoporotic effects of corticosteroids.
Clinical Context:
Has no interactions with steroids or anticonvulsants. It is preferred over praziquantel because of its pharmacokinetic profile and efficacy. Parenchymal disease responds to short courses, but longer duration of therapy (months) may be needed in extraparenchymal disease. In the presence of absolute neutropenia or elevation of transaminases more than 5 times the upper limits of the reference range, albendazole should be withheld until laboratory test results normalize.
Clinical Context:
Increases cell membrane permeability in susceptible worms, resulting in loss of intracellular calcium, massive contractions, and paralysis of musculature. Also produces vacuolization and disintegration of schistosome tegument. This is followed by attachment of phagocytes to parasite and death. It does not cross blood-brain barrier well, only 20% of plasma levels.
Tabs should be swallowed whole with some liquid during meals. Keeping tabs in mouth may release bitter taste that can produce nausea or vomiting. The efficacy appears to be lower than that of albendazole. It works better when taken with cimetidine. Its metabolism can be induced by cytochrome P-450 (corticosteroids, phenytoin, phenobarbital). The serum level of praziquantel is lowered when any of these drugs is coadministered. It is usually considered as a second-line therapy.
Albendazole and praziquantel are antiparasitic drugs used to treat neurocysticercosis. Albendazole has historically been preferred over praziquantel because of its favorable pharmacokinetics profile and efficacy. A recent study has shown that combination therapy may lead to better outcomes.[27] Both agents are cysticidal. These drugs are always administered with corticosteroids. In the presence of absolute neutropenia or elevation of transaminases more than 5 times the upper limits of the reference range, albendazole should be withheld until laboratory test results normalize.[20]
When praziquantel is administered with cimetidine to increase its bioavailability, praziquantel is probably as effective as albendazole in killing viable cysticerci.
Antiparasitic drugs are contraindicated in cysticercal encephalitis (characterized by diffuse cerebral edema), uncontrolled elevated ICP, ocular disease, and subarachnoid neurocysticercosis in close proximity to blood vessels. In all of these cases, steroids should be administered early so that the inflammatory reaction is quelled. Antiparasitic drugs, which may cause release of more antigens and stimulate more inflammation, can then be considered on a case-by-case basis.
Joseph Adrian L Buensalido, MD, Clinical Associate Professor, Division of Infectious Diseases, Department of Medicine, Philippine General Hospital, University of the Philippines Manila College of Medicine; Specialist in Infectious Diseases, Private Practice
Disclosure: Nothing to disclose.
Coauthor(s)
Kingbherly L Li, MD, FPCP, RMT, Chief Fellow, Section of Infectious Diseases, Department of Medicine, Philippine General Hospital, University of the Philippines Manila College of Medicine, Philippines
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
John W King, MD, Professor of Medicine, Chief, Section of Infectious Diseases, Director, Viral Therapeutics Clinics for Hepatitis, Louisiana State University Health Sciences Center; Consultant in Infectious Diseases, Overton Brooks Veterans Affairs Medical Center
Disclosure: Nothing to disclose.
Chief Editor
Pranatharthi Haran Chandrasekar, MBBS, MD, Professor, Chief of Infectious Disease, Department of Internal Medicine, Wayne State University School of Medicine
Disclosure: Nothing to disclose.
Additional Contributors
David Hall Shepp, MD, Program Director, Fellowship in Infectious Diseases, Department of Medicine, North Shore University Hospital; Associate Professor, New York University School of Medicine
Disclosure: Received salary from Gilead Sciences for management position.
Linda S Yancey, MD, Consulting Staff, West Houston Infectious Diseases
Disclosure: Nothing to disclose.
Martin Montes, MD, Fellow, Department of Medicine, Section of Infectious Disease, Baylor College of Medicine; Research Associate, Instituto de Medicina Tropical ‘Alexander von Humboldt’, Universidad Peruana Cayetano Heredia, Perú
Disclosure: Nothing to disclose.
Mossammat M Mansur, MD, MBBS, Attending Physician, Nassau ID Physicians
Disclosure: Nothing to disclose.
Acknowledgements
The authors and editors would like to acknowledge Dr. Martin Montes, Dr. Clinton White Jr., and Dr. Thomas P. Giordano, who were the original authors of this article. They would also like to acknowledge the prior contributions of Dr. John W King to the development and writing of this article.
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