Neurocysticercosis

Introduction and Definition

• Neurocysticercosis (NCC) is a parasitic infection of the central nervous system (CNS) caused by the larval stage (cysticercus) of the pork tapeworm, Taenia solium.
• It is considered the most common parasitic infection of the CNS worldwide and a leading cause of acquired epilepsy, particularly in developing countries.
• The disease is characterized by the presence of cysts in the brain parenchyma, ventricles, subarachnoid space, or spinal cord, leading to a wide spectrum of neurological manifestations.

Epidemiology

• Global Burden: NCC is endemic in most of Latin America, sub-Saharan Africa, and large parts of Asia, including the Indian subcontinent, China, and Southeast Asia.
• Prevalence: It is estimated that millions of people are infected worldwide. In endemic areas, NCC may account for 30–50% of late-onset epilepsy cases.
• Transmission Dynamics:
  • Human cysticercosis is acquired via the fecal-oral route by ingesting T. solium eggs shed in the stool of a human tapeworm carrier.
  • Transmission often occurs within households ("tight clustering") where a family member or domestic servant is a carrier.
  • Autoinfection can occur if a tapeworm carrier ingests their own eggs via fecal-oral contamination or potentially via reverse peristalsis.
  • Crucial Distinction: Ingestion of undercooked pork containing cysticerci leads to intestinal taeniasis (adult tapeworm infection), not directly to NCC. Humans become accidental intermediate hosts (developing cysts) only after ingesting eggs.

Etiology and Life Cycle

• Causative Agent: Taenia solium (pork tapeworm).
• Life Cycle:
  1. Definitive Host (Human): Harbors the adult tapeworm in the intestine (taeniasis). The adult worm sheds proglottids/eggs in feces.
  2. Intermediate Host (Pig): Ingests eggs from human feces. Larvae (oncospheres) hatch, penetrate the gut, and migrate to muscles to form cysticerci.
  3. Human Infection (Taeniasis): Humans eat undercooked pork containing cysticerci. The scolex evaginates and attaches to the intestine, developing into an adult worm.
  4. Human Infection (Cysticercosis): Humans ingest eggs (fecal contamination). Oncospheres hatch in the intestine, penetrate the mucosa, enter the bloodstream, and disseminate to tissues, including the brain, eyes, and muscles, forming cysticerci.

Pathogenesis and Pathology

The pathological changes depend on the location, number, and viability of the cysts, as well as the host's immune response.

Stages of Cyst Evolution

Cysts in the brain parenchyma typically progress through four stages:

1. Vesicular Stage (Viable): The cyst is a fluid-filled vesicle with a thin, transparent wall and an invaginated scolex. The host immune response is minimal (tolerance). The fluid is isodense with cerebrospinal fluid (CSF).
2. Colloidal Stage (Degenerating): The parasite begins to die and loses its ability to evade the immune system. The cyst fluid becomes turbid, and the wall thickens. A vigorous granulomatous inflammatory response occurs, causing perilesional edema. This stage is most often associated with symptoms (seizures) and ring-enhancement on neuroimaging.
3. Granular-Nodular Stage: The cyst collapses, and the content becomes semisolid and granular. Edema subsides, and the lesion begins to mineralize.
4. Calcific Stage (Dead): The parasite is replaced by a calcified granuloma. It appears as a hyperdense nodule on CT. Although "dead," these lesions can periodically release antigens, inciting inflammation and causing recurrent seizures.

Pathophysiological Mechanisms

• Mass Effect: Large cysts or clusters of cysts can compress brain structures.
• Inflammation: Degenerating cysts provoke an inflammatory response, leading to cerebral edema, arachnoiditis, and vasculitis.
• Obstruction: Intraventricular cysts or basilar arachnoiditis can obstruct CSF flow, causing hydrocephalus.
• Epileptogenesis: Inflammation associated with degenerating cysts or chronic gliosis around calcified lesions acts as a focus for seizures.

Clinical Manifestations

The incubation period varies from months to years. Clinical presentation is pleomorphic.

Parenchymal Neurocysticercosis

• Seizures: The most common manifestation, occurring in 50–80% of patients. Seizures are often focal with secondary generalization but can be generalized.
• Single Enhancing Lesion (SEL): A common presentation in children (especially in India), characterized by new-onset focal seizures and a solitary inflammatory granuloma on imaging. Usually has a benign course.
• Cysticercal Encephalitis: Occurs in patients (often children or young women) with a massive burden of inflamed cysts. Presents with signs of raised intracranial pressure (ICP), altered mental status, and seizures due to diffuse cerebral edema. This is a medical emergency.
• Calcified Lesions: Patients may present with chronic epilepsy due to calcified granulomas.

Extraparenchymal Neurocysticercosis

Associated with higher morbidity and mortality.

• Intraventricular Cysts:
  • Can cause obstructive hydrocephalus.
  • Bruns Syndrome: Mobile cysts in the 4th ventricle can act as a ball-valve, causing sudden attacks of headache, vomiting, vertigo, and loss of consciousness with head movement.
• Subarachnoid Cysticercosis:
  • Racemose Form: Cysts in the basal cisterns or Sylvian fissure can lose their scolex and grow as large, budding, grape-like clusters (giant cysts >5 cm). They exert mass effect.
  • Chronic Meningitis: Basilar arachnoiditis causes communicating hydrocephalus, cranial nerve palsies, and entrapment of vessels.
  • Stroke: Vasculitis affecting the circle of Willis can lead to lacunar or large vessel infarcts.
• Spinal Cysticercosis: Rare (1-3%). Can be intramedullary or subarachnoid. Presents with radicular pain, paresthesias, or transverse myelitis.
• Ocular Cysticercosis: Cysts in the retina or vitreous humor can cause visual field defects, chorioretinitis, or retinal detachment.

Diagnosis

Diagnosis is based on a combination of neuroimaging, serology, and clinical/epidemiological criteria.

Diagnostic Criteria (Del Brutto et al.)

• Absolute Criteria:
  • Histologic demonstration of the parasite.
  • Direct visualization of subretinal parasite by fundoscopy.
  • Neuroimaging showing a cystic lesion with a scolex (pathognomonic).
• Major Criteria:
  • Lesions highly suggestive of NCC on neuroimaging (cystic lesions without scolex, enhancing lesions, multilobulated subarachnoid cysts, calcifications).
  • Positive serum enzyme-linked immunoelectrotransfer blot (EITB) for anticysticercal antibodies.
  • Resolution of cystic lesions after cysticidal therapy.
  • Spontaneous resolution of small single enhancing lesions.
• Minor Criteria:
  • Lesions compatible with NCC on neuroimaging.
  • Clinical manifestations suggestive of NCC.
  • Positive CSF ELISA for anticysticercal antibodies or antigen.
  • Cysticercosis outside the CNS.
• Epidemiologic Criteria:
  • Evidence of a household contact with T. solium infection.
  • Individuals coming from or living in an endemic area.
  • History of frequent travel to disease-endemic areas.

Neuroimaging

• Computed Tomography (CT): More sensitive for detecting calcified lesions.
• Magnetic Resonance Imaging (MRI): Superior for evaluating:
  • Posterior fossa and brainstem lesions.
  • Intraventricular and subarachnoid cysts (using FIESTA/CISS sequences).
  • Perilesional edema and inflammation (T2/FLAIR).
  • Vesicular cysts with scolex (hole-in-dot appearance).

Serology

• Enzyme-Linked Immunoelectrotransfer Blot (EITB): The test of choice. Uses purified glycoprotein antigens. Sensitivity is high for multiple cysts (>90%) but lower for single lesions or calcifications (60–80%). Specificity is near 100%.
• ELISA: Less specific (cross-reacts with other helminths) and less sensitive than EITB. Not recommended as a primary diagnostic tool.
• Antigen Detection: Detection of parasite antigen in CSF or serum indicates viable parasites. Useful for monitoring treatment response in subarachnoid disease.

Management

Management is multimodal, involving symptomatic treatment, antiparasitic drugs, anti-inflammatory agents, and surgery. Therapy must be individualized based on the location, number, and viability of cysts.

Symptomatic Treatment

• Antiepileptic Drugs (AEDs): Primary management for patients presenting with seizures. Monotherapy (e.g., phenytoin, carbamazepine, levetiracetam) is usually effective. AEDs can often be tapered after resolution of acute lesions, but calcified lesions may require long-term therapy.
• Management of Hydrocephalus: Priority over antiparasitic therapy. Requires CSF diversion (ventriculoperitoneal shunt) or endoscopic third ventriculostomy.

Antiparasitic Therapy

Indications and regimens depend on the type of NCC.

• Contraindications: Antiparasitic drugs should not be used in:
  • Cysticercal Encephalitis: Massive release of antigens from dying cysts can worsen cerebral edema and cause herniation. Treatment is high-dose steroids and osmotic agents.
  • Ocular Cysticercosis: Inflammation can cause blindness. Surgical removal is preferred.
  • Untreated Hydrocephalus: Elevated ICP must be managed first.
  • Calcified Cysts: The parasite is dead; treatment offers no benefit.

Drug Regimens

• Albendazole: Generally preferred due to better penetration into CSF and cysticidal efficacy.
  • Dose: 15 mg/kg/day (divided into 2 doses).
  • Administration: With a fatty meal to increase absorption.
• Praziquantel:
  • Dose: 50 mg/kg/day.
• Combination Therapy: Studies show enhanced efficacy for multiple cysts.
  • 1–2 Parenchymal Cysts: Albendazole monotherapy (15 mg/kg/day) for 10–14 days is recommended.
  • >2 Parenchymal Cysts: Combination of Albendazole (15 mg/kg/day) + Praziquantel (50 mg/kg/day) for 10–14 days results in better cyst resolution.

Corticosteroid Therapy

• Rationale: To control the inflammatory response (edema) caused by dying parasites during antiparasitic treatment.
• Regimen: Prednisone (1 mg/kg/day) or Dexamethasone (0.1 mg/kg/day) is usually started 1 day before or simultaneously with antiparasitic drugs and continued for the duration of therapy, followed by a taper.
• Subarachnoid Disease: High-dose, prolonged steroids (e.g., Dexamethasone 0.2–0.4 mg/kg/day) are critical to prevent vasculitis and entrapment neuropathy.

Surgical Management

• Hydrocephalus: VP shunt placement. Shunt failure rates are high due to proteinaceous debris/cells; concurrent steroid and antiparasitic therapy can reduce failure.
• Intraventricular Cysts: Neuroendoscopic removal is the treatment of choice, especially for the third and lateral ventricles. It is minimally invasive and avoids shunt dependence.
• Giant/Racemose Cysts: May require surgical debulking or decompression if mass effect is life-threatening.

Prevention

• Sanitation: Improved disposal of human feces to prevent pig infection.
• Pig Husbandry: Confining pigs and preventing access to human feces.
• Meat Inspection: Identification and condemnation of infected pork.
• Cooking: Thorough cooking or freezing of pork to kill cysticerci.
• Mass Chemotherapy: Treating human tapeworm carriers (taeniasis) with praziquantel or niclosamide to reduce egg shedding.
• Vaccination: Vaccination of pigs is a strategy for long-term control.