Neurocysticercosis

Neurocysticercosis (NCC) is the most common parasitic disease of the nervous system and is the main cause of acquired epilepsy in developing countries. It has also been a problem in industrialized countries because of the immigration of tapeworm carriers from areas of endemic disease.[9, 10]

Neurocysticercosis can be acquired via fecal-oral contact with carriers of the adult tapeworm Taenia solium. This usually indicates the presence of a tapeworm carrier in the immediate environment (ie, household) or by accidental ingestion of contaminated food. Cases of auto-ingestion, in which persons with taeniasis may ingest the eggs of T solium into their intestine, have been reported.

An example of an image of human neurocysticercosis is provided below.

Massive nonencephalitic neurocysticercosis. Photo courtesy of Cysticercosis Working Group in Peru.

See also Neuroimaging in Neurocysticercosis.

Neurocysticercosis is the result of accidental ingestion of eggs of Taenia solium (ie, pork tapeworm), usually due to contamination of food by people with taeniasis. T solium has a 2-host biologic cycle, with humans as the definitive hosts carrying the intestinal tapeworm, and pigs as the normal intermediate hosts harboring the larvae or cysticerci. This parasite has a head (scolex) with 4 suckers and a double crown of hooks, an unsegmented neck, and a large body with several hundreds of hermaphrodite proglottids.

Cysticerci are ingested by humans through poorly cooked infected pork. Cysts evaginate in the small intestine, attach to the wall by its suckers and hooks, and develop strobila or chains of proglottids. From the distal end of the strobila, fertile eggs are excreted into the gravid proglottids. Up to 60,000 eggs may be contained in a proglottid.

Pigs ingest stool contaminated with Taenia eggs, the embryos actively cross the intestinal wall, get into the bloodstream, and are transported to most tissues, where they reside as cysticerci. Larvae are found most commonly in the central nervous system (CNS), but they can also be located in the eye, muscle, or subcutaneous or other tissues.

Neurocysticercosis is the most common parasitic infection of the central nervous system (CNS). Approximately 2.5 million people worldwide carry the adult tapeworm, and many more are infected with cysticerci.

In the United States, neurocysticercosis is mainly a disease of immigrants, and the disease is prevalent in the states of California, Texas, and New Mexico. Neurocysticercosis represents a major cause of morbidity among the Hispanic population. Although most of the cases have been diagnosed in persons of Hispanic origin, the incidence is increasing in nonendemic countries because of travel to zones of endemic disease. Native cases have also been reported, presumably because of ingestion of infected food that was handled by carriers of T solium.

The incidence of neurocysticercosis has been steadily increasing in the United States. Although still mostly prevalent in the southwestern United States, imported cases have been reported throughout the country.

Globally, neurocysticercosis is endemic in Central and South America, sub-Saharan Africa, and in some regions of the Far East, including the Indian subcontinent, Indonesia, and China, reaching an incidence of 3.6% in some regions. This disease is rare in Eastern and Central Europe, in North America (with the exception of Mexico), and in Australia, Japan, and New Zealand, as well as in Israel and in the Muslim countries of Africa and Asia.

Cysticercosis can be seen in immigrant populations with a relatively high frequency, as in the US Southwest and South Africa, and subcutaneous cysticercosis is more common in Asian populations than in other peoples of other areas of endemic disease. It is not clear whether this is due to variations in parasite strain or to those in the host.

Although neurocysticercosis appears to affect men and women equally, there is some evidence to suggest that inflammation around the parasites may be more severe in women than in men.[11] In addition, despite the fact that neurocysticercosis appears to be the most frequent cause of seizures in children[12] and adults (peak incidence, 30-40 y), the exact incidence in children is not known.

In most patients with neurocysticercosis, the prognosis is good. Associated seizures seem to improve after treatment with anticysticercal drugs and, once treated, the seizures are controlled by a first-line antiepileptic agent. Duration of treatment, however, is not defined.

No figures are available for the burden of mortality associated with neurocysticercosis. However, the racemose[13] form of this disease—which appears macroscopically as groups of cysticerci, often in clusters that resemble bunches of grapes located in the subarachnoid space—is associated with poor prognosis and elevated mortality rate (>20%).

Neurocysticercosis-associated epilepsy is an important cause of neurologic morbidity,[14] and chronic epilepsy is one of the most frequent complications of neurocysticercosis. Others include headaches, neurologic deficits related to strokes, and hydrocephalus. Patients with complications such as hydrocephalus, large cysts, multiple lesions with edema, chronic meningitis, and vasculitis are acutely ill and do not respond very well to treatment. Frequently, they have complications due to medical and surgical therapy.

Neurocysticercosis is a major public health problem in developing countries and is emerging as an increasingly important condition in regions in which the disease is not endemic. Comprehensive programs of long-term intervention involve appropriate legislation, health education, modernization of swine husbandry practices, improvement of efficiency and coverage of meat inspection, provision of adequate sanitary facilities, and measures to detect and treat human tapeworm carriers.

Political and economic realities in many communities where T solium is endemic today provide little hope that all these goals can be achieved in the near future. However, short-term approaches can be effective in the long-term, and these include educational campaigns in personal hygiene and general sanitation within the disease-endemic area.

Note that the usual restrictions for patients with epilepsy would be applicable for patients with neurocysticercosis presenting with seizures.

Neurocysticercosis is a pleomorphic disease, although it sometimes produces no clinical manifestation. This pleomorphism is due to variations in the locations of the lesions, the number of parasites, and the host's immune response.[3]

Many patients are asymptomatic; others report vague symptoms such as headache or dizziness. The onset of symptoms is usually subacute to chronic, with the exception of seizures, which present in an acute fashion. Possible symptomatic presentations are briefly reviewed below.

Epilepsy

Epilepsy is the most common presentation (70%) of neurocysticercosis and is also a complication of the disease.[14] Neurocysticercosis is the leading cause of adult-onset epilepsy and is probably one of the most frequent causes of childhood epilepsy in the world.

Seizures secondary to neurocysticercosis may be generalized or partial. Simple and complex partial seizures may be associated with the presence of a single lesion. Generalized seizures are usually tonic-clonic; this is thought to be related to the presence of multiple lesions. However, irritation of focal cortical tissue by one of the lesions most probably leads to focal onset with secondary generalization. Myoclonic seizures also have been described.

Go to First Adult Seizure for complete information on this topic.

Headache

Headaches may be associated with intracranial hypertension and are indicative of hydrocephalus; they may also result from meningitis. Chronic headaches may be associated with nausea and vomiting (simulating migraines).

Intracranial hypertension

Most often, intracranial hypertension is due to obstruction of cerebrospinal fluid (CSF) circulation caused by basal or ventricular cysticercosis. It may also result from large cysts displacing midline structures, granular ependymitis, arachnoiditis, or the so-called cysticercotic encephalitis caused by the inflammatory response to a massive infestation of cerebral parenchyma with cysticerci. Affected patients may have seizures and deterioration of their mental status, mainly due to the host's inflammatory reaction as an exaggerated response to the massive infestation.

Diplopia may also result from intracranial hypertension or arachnoiditis producing entrapment or compression of cranial nerves III, IV, or VI.

Strokes

Ischemic cerebrovascular complications of neurocysticercosis include lacunar infarcts[15] and large cerebral infarcts due to occlusion or vascular damage. Hemorrhage can also occur and has been reported as a result of rupture of mycotic aneurysms of the basilar artery. Strokes may be responsible for paresis or plegias, involuntary movements, gait disturbances, or paresthesias.[16]

Neuropsychiatric disturbances

Neuropsychiatric dysfunction can range from poor performance on neuropsychologic tests to severe dementia. These symptoms appear to be related more to the presence of intracranial hypertension than to the number or location of parasites in the brain.

Hydrocephalus

Ten to thirty percent of patients with neurocysticercosis develop communicating hydrocephalus due to inflammation and fibrosis of the arachnoid villi or inflammatory reaction to the meninges and subsequent occlusion of the foramina of Luschka and Magendie. Noncommunicating hydrocephalus may be a consequence of intraventricular cysts.

Presentations of other forms of neurocysticercosis

Patients with intrasellar neurocysticercosis present with ophthalmologic and endocrinologic manifestations mimicking those of pituitary tumors.

Spinal neurocysticercosis is rare and may be either intramedullary or extramedullary. The extramedullary form is the most frequent and is responsible of symptoms of spinal dysfunction such as radicular pain, weakness, and paresthesias. Intramedullary presentation may cause paraparesis, sensory deficits with a level, and sphincter disturbances.

Ocular cysticercosis occurs most commonly in the subretinal space. Patients may present with ocular pain, decreased visual acuity, visual field defects, or monocular blindness.

Systemic cysticercosis is most common in the Asian continent. The parasites may be located in the subcutaneous tissue or muscle. Peripheral nerve involvement as well as involvement of the liver or spleen have been reported.

Twenty percent or less of infected patients with neurocysticercosis have abnormal neurologic findings. Physical findings depend on where the cyst is located in the nervous system and include the following:

• Cognitive decline

• Dysarthria

• Extraocular movement palsy or paresis

• Hemiparesis or hemiplegia, which may be related to stroke, or Todd paralysis

• Hemisensory loss

• Movement disorders

• Hyper/hyporeflexia

• Gait disturbances

• Meningeal signs

Neurocysticercosis is commonly diagnosed with the routine use of diagnostic methods such as computed tomography (CT) and magnetic resonance imaging (MRI) of the brain. Peripheral leukocytosis, eosinophilia, and elevated erythrocyte sedimentation rate may be found on routine blood work.

See also Neuroimaging in Neurocysticercosis.

Reports have shown a decrease in N -acetyl aspartate (NAA) and creatine levels and elevated lactate and metabolites such as alanine and succinate on magnetic resonance spectroscopy. For the purpose of localization, myelography and cerebral angiography, as well as cisternographies and ventriculographies, may be used.

Analysis of the cerebrospinal fluid (CSF) is indicated in every patient presenting with new-onset seizures or neurologic deficit in whom neuroimaging shows a solitary lesion but does not offer a definitive diagnosis.

This study is contraindicated in cases of large cysts causing severe edema and displacement of brain structures, as well as in lesions causing obstructive hydrocephalus.

When parasites are located in the brain parenchyma, results of CSF analysis may be normal. The results are usually abnormal (50-80%) when parasites are present in the basal cisterns or in the ventricles.

CSF findings include mononuclear pleocytosis, normal or low glucose levels, elevated protein levels, high immunoglobulin G (IgG) index, and in some cases, the presence of oligoclonal bands. Eosinophilia (5-500 cells/µL) in the CSF suggests neurocysticercosis; however, eosinophils also are elevated in neurosyphilis and tuberculosis of the central nervous system (CNS).[4]

Taeniasis and neurocysticercosis coexist in 10-15% of patients with neurocysticercosis. One study reported that intestinal taeniasis is very common in patients with massive infestation with cysticerci but without cysticercotic encephalitis.

Tapeworm carriers may be identified by examining the stool of the relatives of a patient with cysticercosis encephalitis. Specific co-proantigen detection by enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) may help improve the screening of carriers in endemic areas.

Enzyme-linked immunosorbent assay (ELISA) is the most widely used test of cerebrospinal fluid (CSF); it has a sensitivity of 50% and a specificity of 65% for neurocysticercosis.

Enzyme-linked immunoelectrotransfer blot (EITB) assay in serum using lentil lectin glycoprotein antigens of T. solium cysts is also highly sensitive and specific, initially described as 98% and 100%, respectively for detection of antibodies in serum and cerebrospinal fluid.

In patients with more than two lesions, 90% sensitivity has been reported. This declines to 50-62% with a single lesion and for calcified lesions.

Using monoclonal antibodies to detect circulating parasitic antigens may be helpful in monitoring response to cysticidal therapy.

Computed tomography (CT) scanning is the preferred imaging study for detection of parenchymal calcifications (see the image below).

Computed tomographic (CT) scan of the brain in a patient who presented with an episode of generalized tonic-clonic seizure. Note the calcified lesion in the left parieto-occipital region. Subsequent evaluation confirmed the diagnosis of neurocysticercosis.

Depending on the stage of evolution of the infestation, the findings are variable, as follows:

• Vesicular stage (viable larva): Hypodense, nonenhancing lesions are seen.

• Colloidal stage (larval degeneration): Hypodense/isodense lesions with peripheral enhancement and perilesional edema are seen.

• Nodular-granular stage: Nodular-enhancing lesions are observed.

• Cysticercotic encephalitis: Diffuse edema, collapsed ventricles, and multiple enhancing parenchymal lesions are characteristic.

• Active parenchymal stage: The scolex within a cyst may appear as a hyperdense dot.

• Calcified stage: When the parasite dies, nodular parenchymal calcifications are seen.

Magnetic resonance imaging (MRI) is the imaging modality of choice for neurocysticercosis, especially for evaluation of intraventricular and cisternal/subarachnoidal cysts (see the following images). Noninvasive magnetic resonance cisternography (MRC) or fluid-attenuated inversion recovery (FLAIR) sequences before and after inhalation of 100% oxygen may provide better detection, especially of small racemose cisternal cysts.

T2-weighted magnetic resonance image (MRI) of the brain showing the presence of increased signal as a result of edema in the right frontal region; subsequent studies found a cysticercus in that location.

Magnetic resonance image (MRI) of the brain in a patient who presented with an episode of generalized tonic-clonic seizure. Note the cyst in the left parieto-occipital region with perilesional edema.

Magnetic resonance studies are also more helpful in the evaluation of cystic degeneration and pericystic inflammatory reaction. Findings on MRI include the following:

• Vesicular stage: Cysts follow the cerebrospinal fluid (CSF) signal. T2 hyperintense scolex may be seen, no edema, and usually no enhancement.

• Colloidal stage: Cysts are hyperintense to the CSF. There is surrounding edema, and the cyst wall enhances.

• Nodular-granular stage: The cyst wall thickens and retracts, there is a decrease in edema, and nodular or ring enhancement is present.

Only in extreme cases of neurocysticercosis is a brain biopsy necessary. A trial of anticysticercal drugs with follow-up imaging shortly thereafter (ie, 2 months) is recommended before considering biopsy.

A cysticercus is a liquid-filled vesicle with a 3-layer wall and scolex, although the scolex may not be found. The parasite can adopt 3 different presentations in the nervous system—cystic, racemose, and mixed form.

The cystic form refers to the presence of cysts anywhere in the brain; the cysts are approximately 7 mm in diameter and may be single or multiple. Their most frequent locations are the leptomeninges and the cerebral cortex.

The racemose form refers to the presence of multiple cysts in the basal cisterns where the vesicles can have different sizes, and the cysts can be attached to the meninges[13] ; they do not have a scolex. Because of their location, the racemose form can produce hydrocephalus, which is caused by inflammation of meninges with subsequent fibrosis and obstruction. Sometimes they give the impression of an "infiltrative" aspect (Trelles "canceriform" presentation[17] ).

The mixed form refers to the presence of both of the cystic and racemose forms.

Treatment of neurocysticercosis depends upon the viability of the cyst and its complications.[5] Management includes symptomatic treatment as well as treatment directed against the parasite.[18]

If the parasite is dead, the treatment is directed primarily against the symptoms (eg, anticonvulsants for management of seizures). Monotherapy is usually sufficient. Duration of the treatment remains undefined, and depends neither on the type of seizure at presentation nor on other risk factors for recurrence, such as age at onset and number of seizures before diagnosis. Calcification remains an epileptogenic focus. Treating patients with viable cysts with a course of anticysticercal drugs in order to achieve better control of seizures is common practice.

If the parasite is viable or active and the patient has vasculitis, arachnoiditis, or encephalitis, a course of steroids or immunosuppressants is recommended before the use of anticysticercal drugs. Antiparasitic treatment[6] with albendazole is also useful in cysticercosis of the racemose type.

If only parenchymal, subarachnoid, or spinal cysts are present without the complications mentioned previously (eg, chronic epilepsy, headaches, neurologic deficits related to strokes, and hydrocephalus), anticysticercal treatment can be considered, with the concomitant use of steroids, even in patients with massive brain infection. Reports indicate that multiple trials with anticysticercal treatment may be required for giant subarachnoid cysts.

Guidelines issued in April 2013 by the American Academy of Neurology recommend use of albendazole plus a corticosteroid for the treatment of parenchymal neurocysticercosis.[1] The guideline, which is also endorsed by the American Epilepsy Society, recommends treatment with albendazole (400 mg twice daily for adults or weight-based dosing for either adults or children) plus either dexamethasone or prednisolone to decrease the number of active lesions on brain imaging studies and reduce long-term seizure frequency.[2]

A double-blind, placebo-controlled study showed that in patients with seizures due to viable parenchymal cysts, antiparasitic therapy decreases the burden of parasites and is safe and effective, at least in reducing the number of seizures with generalization.[7]

In the presence of hydrocephalus due to an intraventricular cyst, placement of a ventricular shunt is recommended, followed by surgical extirpation of the cyst and subsequent medical treatment.[8]

In cases of multiple cysts in the subarachnoid space (ie, the racemose form), surgical extirpation, on an urgent basis, is recommended. If the obstruction is due to arachnoiditis, placement of a ventricular shunt should be followed by administration of steroids and subsequent medical therapy.

Because of frequent shunt dysfunctions due to entry of inflammatory tissue as well as parasitic debris inside the ventricular cavities, Sotelo designed a device that functions at a constant flow without the valvular mechanism of Pudenz-type shunts.

Surgical treatment in the particular case of medically refractory epilepsy due to a single lesion has been reported. Evaluation in an epilepsy center is indicated.

Neuroendoscopy is a tool with great potential for use in the management of ventricular cysticercosis.

Most patients with ocular or spinal lesions require surgical management.[19]

Intracerebral cysticercotic lesions can cause epilepsy in the future. Administration of antiepileptic medication is the same as in any other epileptic syndrome.

Follow-up imaging study is recommended after 2-3 months following treatment, especially in cases in which anticysticercal medications are used as a diagnostic tool. The use of imaging will guide the requirement of future trials of anticysticercal medication in cases of subarachnoid cysticercosis.

The goals of pharmacotherapy for neurocysticercosis are to reduce morbidity, prevent complications, and eradicate the infestation.

Medication for taeniasis is required in patients with a concomitant intestinal infection. Niclosamide is an antiparasitic medication that is not absorbed in the gastrointestinal system, which allows its concomitant use with anticysticercal treatment. However, this agent is not available in the United States.

Class Summary

Two medications are available in the treatment of neurocysticercosis, praziquantel (PZQ) and albendazole.[20, 21] Both agents eliminate the cysticerci or markedly reduce their number. Albendazole appears to be superior to PZQ and seems to be more effective in giant cysts[22] and subarachnoid, intraventricular, or spinal neurocysticercosis.

Use of these medications may result in further increases in intracranial pressure in patients with cysticercal encephalitis and hydrocephalus. Hence, they should be used only after a ventricular shunt has been placed in these forms of neurocysticercosis.

Drugs such as dexamethasone, phenytoin, or carbamazepine may decrease plasma levels of PZQ due to interaction with the cytochrome P-450 microsomal system.[23] This is not seen with albendazole (which is excreted unchanged in the urine). Simultaneous administration of dexamethasone appeared to increase plasma levels of albendazole and decreased its rate of elimination.

Praziquantel (Biltricide)

Praziquantel is an isoquinolone that destroys the scolex, produces paralysis of the parasite musculature, and causes extensive integumental destruction, followed by an inflammatory reaction.

Albendazole (Albenza)

Albendazole decreases ATP production in the worm, as well as inhibits polymerization of a component of the microtubules, thus preventing their formation. This causes energy depletion, immobilization, and finally death of the parasite. To avoid an inflammatory response in the central nervous system (CNS), patients also must be started on anticonvulsants and high-dose glucocorticoids.

Class Summary

In case of seizures with calcification, administration of a first-line antiepileptic drug is the most suitable treatment. In patients with viable cysts, the treatment needs to be combined with anticysticercal drugs. The use of newer antiepileptic medications (eg, valproic acid, lamotrigine, levetiracetam, topiramate, zonisamide) has not been evaluated in this particular condition, but they may be equally effective.

Phenytoin (Dilantin, Phenytek)

Phenytoin may act in the motor cortex where it may inhibit the spread of seizure activity. Activity of the brainstem centers that are responsible for the tonic phase of grand mal seizures may be also inhibited.

The dose of phenytoin should be individualized. Administer a larger dose before the patient retires to bed if the dose cannot be divided equally.

Carbamazepine (Tegretol, Carbatrol, Epitol, Equetro)

Carbamazepine is used for the management of partial seizures. This drug blocks sodium channels and inhibits high-frequency repetitive firing. Carbamazepine also acts presynaptically to decrease synaptic transmission.

Phenobarbital

Phenobarbital is useful in the treatment of partial seizures and generalized tonic-clonic seizures. This agent enhances gamma-aminobutyric acid (GABA)-mediated inhibition and reduces glutamate-mediated excitation, thereby elevating the seizure threshold and limiting the spread of seizure activity.

Class Summary

Glucocorticoid drugs are used for the management of complications due to neurocysticercosis.

Dexamethasone (Baycadron, Maxidex, Ozurdex)

Dexamethasone is a concomitant medication used for the management of reactions to anticysticercal treatment in parenchymal, subarachnoid, or spinal cysts and in the presence of vasculitis, arachnoiditis, or encephalitis.

Class Summary

Diuretic (osmotic) drugs may reduce intracranial pressure and cerebral edema by creating an osmotic gradient across an intact blood-brain barrier. As water diffuses from the brain into the intravascular compartment, intracranial pressure decreases.

Mannitol (Osmitrol)

Mannitol may reduce subarachnoid space pressure by creating an osmotic gradient between the cerebrospinal fluid (CSF) in arachnoid space and the plasma. However, this agent is not indicated for long-term use.