Neurocyscticercosis

Dr. Yusuf Imran

M.D Pediatrics

J.N Medical College, Aligarh, India

Introduction

Neurocysticercosis (NCC) is the infection of the CNS by the larval stage of thepork tapeworm Taenia solium.

Infection may develop in any organ- CNS (parenchyma, subarachnoid spaces,ventricles and spinal cord), eyes and muscles are the most commonly involved.

Most common manifestation is epilepsy but can have several other neurologicalmanifestations.

Epidemiology

NCC is endemic in most Latin American countries, sub-Saharan Africa, and large regions of Asia (including Indian subcontinent and China).

Rare in developed countries, can occur in travelers/immigrants.

A study from North India found point prevalence of NCC - 4.5/1000. In pig farming community it is upto 15 %.

Proportion of NCC among patient with epilepsy is estimated @ 29 %. In those with partial seizures it was >50 %.

Life cycle of Taenia solium

Taenia solium requires two hosts to complete its life cycle.

Pigs (intermediate host) contain the cystecerci, primarily in muscle.

Humans (definitive host) infected by consuming undercooked pork containing liveT.solium cysticerci.

Cysticerci develop into adult tapeworm which releases eggs in human feces.

Eggs contaminate soil/vegetation, when ingested by pigs/humans eggs develop intolarvae which pass through intestinal mucosa and reach various tissues.

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Growth stages of Taenia solium:

A-Infective T.solium eggs, B-Larva or cysticercus, C-Evaginating cysticercus, D-Tapeworm scolex, E-Tapeworm strobilaL

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Modes of infection

Sources of infection- persons with Taeniasis (acquired from pork).

Transmission ways-

not spread from person to person directly

persons with Taeniasis will shed tapeworm eggs in their bowel movements

Modes of infection

Infection can happen by accidentally swallowing pork tapeworm eggs

Through-

drinking contaminated water or food

by putting contaminated fingers to mouth (external autoinfection)

by internal autoinfection

Disease spectrum of T.solium

Taeniasis = adult tapeworm in small intestine

• Usually asymptomatic (eggs or proglottids in feces)

• Vague abdominal symptoms

Cysticercosis = T. solium larvae in human tissues (eg, muscle)

• Usually asymptomatic

• Painless subcutaneous nodules in arms and chest

Neurocysticercosis (NCC) = cysts in the central nervous system

• Most severe manifestation

Etiopathogenesis

Clinical expression, management and prognosis of NCC varies depending onthe number of CNS lesions, their stage, size, location and host inflammatoryresponse.

Studies have identified a number of mechanisms used by the cycticercus tomodulate host’s immune response.

• Protease inhibitor- Taeniaestatin

• Sulfated polysaccharides

• Parasite paramyosin

• Prostaglandins

• Stimulate antibody production

Etiopathogenesis

Although, cysticerci reach mature size within a few weeks, there a periodof several years between exposure and onset of symptoms.

When parasite degenerates there is a brisk inflammatory response.

The seizures are thought to result not from the parasitic infection per se,but from the host response.

Types of Neurocysticercosis

1. Intraparenchymal NCC

Most common form, seen at grey white matter junction.

Single or Multiple.

Range in size from a few mm to 1 to 2 cm.

Commonly seen in children >5 years but can occur in toddlers and infants.

Types of Neurocysticercosis

Intraparenchymal NCC cont…

Seizures are most common manifestation of intraparenchymal NCC.

1/3rd may have associated headache and vomiting.

Papilloedema occurs in 2 to 7 %.

Neurological deficits seen in 4 to 6 %.

Seizures respond well to monotherapy.

Cysticercal Encephalitis- results from large number of cysticeci in brain parenchyma with diffuse inflammation and edema.

Types of Neurocysticercosis

The parenchymal cysts evolve through 4 stages-

The vesicular cyst

Colloidal stage

Granular nodular stage

Nodular calcified stage

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Types of Neurocysticercosis

2. Extraparenchymal NCC

Ventricular NCC- can obstruct CSF flow causing hydrocephalus. CT may reveal only hydrocephalus and no cysticerci.

Subarachnoid NCC- can occur in the gyri, fissures, basilar cisterns.

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Types of Neurocysticercosis

Other forms of Cysticercosis

Spinal Cysticercosis (intramedullary/extramedullary)

Ocular Cysticercosis

In Muscles

In Subcutaneous tissue

Other organs

A single patient may have multiple types and locations of cysticercus.

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Clinical Manifestations

Asymptomatic.

Most common manifestation is Seizure (focal, secondary generalized orgeneralized). (80%)

Headache is common (unilateral/bilateral)- may reflect raised ICT or vasculitis.

Focal neurological deficits (16%)

Symptoms/signs of raised ICT-nausea, vomiting, altered mental status, visualchanges, dizziness, cerebral edema. (12%)

Neurocognitive defects- leaning disability, psychosis, depression. (5%)

Imaging

CT

Parenchymal cysts- usually appear as single, small (<20mm) with ring/diskenhancement and eccentric hyper dense scolex. Multiple lesions give ‘starrysky’ appearance. (colloidal stage).

Enhancement indicates inflammation. Live vesicular cysts are non-enhancing.

Extra-parenchymal cysts- may show hydrocephalus, enhancement oftenctorium and basal cisterns and occasionally infarcts.

ImagingMRI

Superior to CT in detecting cysts in ventricles, posterior fossa, brainstem,small cysts.

Small calcified lesions may be missed.

Magnetization transfer images (MT) and magnetization transfer ratio (MTR),recovery (FLAIR) and fast imaging employing steady-state acquisition(FIESTA) sequences for lesions not visible on routine MRI.

Serological Tests

Seropositivity depends on parasite load and endemicity. False positive and falsenegative results can occur.

False-negative result:

Single lesions

Calcification

False-positive:

Other parasitic infections

High percentage of false positive for patients from endemic area

Serological Tests

EITB assay- uses lentil lectin purified glycoprotein antigens (LLGP) to detectantibodies to T soliumin in serum. Sensitivity 98% (multiple parasites), 50-70 %(solitary cysticercus).

Detection of anticysticercal antibodies in the CSF by ELISA.

Detection of circulating parasitic antigens in serum by ELISA with monoclonalantibodies is experimental.

In patients with reliable diagnosis of NCC by imaging studies, immunological test is notrequired, since a negative test will not discard a NCC.

Other lab tests…

Eosinophilia may occur.

CSF-

Usually done to rule out other causes.

Can be normal in inactive disease.

Moderate pleocytosis (mostly mononuclear cells; upto 300/mm3), increasedprotein (50-300 mg/dl). Correlate with disease activity and whether or not theparasites are located in sub-arachnoid space.

Other lab tests…

Biopsy of subcutaneous nodules.

Radiographs of skeletal muscles.

Specific coproantigen detection by ELISA for screening for T solium carriers.

Stool examination for T.solium eggs has poor sensitivity.

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Definitive diagnosis- oneabsolute criterion or two majorplus one minor and oneepidemiologic criteria

Probable diagnosis- one majorplus two minor criteria, one majorplus one minor and oneepidemiologic criteria, threeminor plus one epidemiologiccriteria.

Differential diagnosis

Tuberculoma

(presence of raised ICT, progressivefocal neurodeficit, size >20mm,lobulated irregular shape, midline shift& marked edema, lesions at base ofbrain)

Special MRI sequences – diffusionweighted MRI and proton magneticresonance spectroscopy (MRS) arebeing tried.

Case discussion- A two month old child was referred for

evaluation of fever associated with fits. Plain CT brain showeda 1.1.x 1.0 cms. round hypodense lesion in the right frontallobe. There was dilatation of all the ventricles, basal cisterns.The anterior fontanalle was bulging. On contrast study therewas dense enhancement of basal meninges, dense ringenhancement ( 4 mm thick ) of the the right frontal lobelesion.

Differential diagnosis

Microabscesses

Toxoplasmosis

Fungal lesions

Low grade astrocytoma

Cystic cerebral metastasis

CNS lymphoma

Management

Emergency care

Manage seizure activity

Supportive care (A-B-C)

Monitor, and correct metabolic abnormalities

Anticonvulsants are effective.

Evidence of increased ICP- Steroids, osmotic agents, and/or diuretics

Initiate proper diagnostic procedures

Blood work and imaging

ManagementIntraparenchymal NCC- Symptomatic treatment, anti-parasite treatment or

surgery ?

Calcified cysts only- antiepileptic, analgesic, and anti-inflammatory drugs; forseizures relapses, repeat imaging looking for peri-calcification oedema. AED for at least2yrs since last seizure. No anti-parasite drugs.

*One or more cystic or degenerating lesions- antiepileptic, analgesic, and anti-inflammatory drugs; antiparasitic treatment under hospital conditions with steroidtreatment. Discontinue AED in single lesions after they resolve (without calcification).

*Level 1 evidence

Cysticercal encephalitis- Manage intracranial hypertension; do not use antiparasiticdrugs.

Management

Asymptomatic parenchymal lesions

• Prophylactic AED not justified in calcified lesions without seizures.

• Viable cysts- Give prophylactic AED when antiparasite treatment is alsoplanned.

Repeat neuroimaging after 3-6 m to document lesion resolution. Repeatcourse of cysticidal therapy if persistent lesion.

Management

Drugs:

• Albendazole- 15mg/kg/day in 2-3 divided doses for 2-4 weeks. Shortercourses of 3 to 14 days tried in single lesions.

• Praziquintal- 50mg/kg/day, less effective than albendazole.

• Combinations of two antiparasitic drugs- increased cyst clearance inmultiple lesions.

• Steroids-

Dexamethasone- 0.1 mg/kg/day i.v starting one day before antiparasitedrugs, give for 1 to 2 weeks then taper.

Prednisolone- 1 to 2 mg/kg/day.

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ManagementExtraparenchymal NCC

Management

Other forms of NCC

Spinal- Intramedullary cysts are treated with surgery, albendazole withsteroids is being tried. Subarachnoid cysts can migrate so imaging is donejust before surgery.

Ocular- Surgical management is the standard of care.

Prognosis

Single lesions- good prognosis, disappears in >60% at 6m.

Seizure recurrence is 10-20% with single lesions, multiple lesions havemore frequent seizures.

Prognosis is poorer in cysticercal encephalitis and extraparenchymalNCC.

Prevention

T solium infection is one of a few diseases targeted for focalelimination and eventual eradication by the International Task Forcefor Disease Eradication.

Public education, proper hygiene, provision for toilets.

Safe handling of meat, strict animal husbandry and meet inspectionsprocedures.

Prevention

Mass deworming of population with Niclosamide or Praziquintal.

Mass vaccination of pigs and treatment of pigs with Oxfendazole.

Community interventions reduce rate of epilepsy in hyper-endemic areas.

Conclusion

NCC is a common cause of seizures and other neurological manifestationsand needs to be considered in D/D of many neurological conditions.

Treatment with cycticidal therapy leads to reduction in seizure frequencyand faster resolution of lesions.

Children with a single or few lesions have a good outcome.

Prevention of NCC is important and feasible.

Thank you