Neurocysticercosis

NEUROCYSTICERCOSIS

Abdulrahman MohammedSchool of Public Health & Zoonoses

INTRODUCTION

Cysticercosis is a disease caused by the presence of Cysticercus cellulosae and Cysticercus racemose, the

larval forms of Taenina solium Cysticercus bovis, the larval form of T. saginata

occurs very rarely in manA new species, T. asiatica was described in 1993

Neurocysticercosis – cysticerci (larval form) form in the brain

NEUROCYSTICERCOSIS• NCC is due to the development of Taenina solium

cysticerci in the human central nervous system, where parasites can be found in the parenchyma, the subarachnoid tissue, and the ventricles

• 26.3% to 53.8% active epilepsy cases in the developing world including India and Latin America are due to NCC. It is also becoming more common in the developed world because of increased migration of people with the disease or Taenia solium carriers and frequent travel to the endemic countries.

Tapeworms

HISTORY• Cysticercosis was first described in pigs by

Aristophanes and Aristotle in 3rd century BC. • Later it was noticed in human by Parunoli in 1550. • Cysticercosis has also been described in ancient Indian

medical book, the Charak Sanhita.• NCC was first reported in a coolie from Madras, who

died due to seizure and was found to be infected with cyst on autopsy (Armstrong 1888).

• In 1912, Krishnaswamy (1912) reported cysticerci related case of muscle pains and subcuataneousnodules with abundant cysticerci in the muscles, heart and brain at autopsy.

• In 1934, high rate of new onset epilepsy related to cysticercosis in the British army deployed in India was noticed (MacArthur 1934).

Two different theories explain the origin of tapeworms.

1) Domestication of animals 10,000 years ago

Two different theories explain the origin of tapeworms.

2) Scavenging of food 2 million years ago by African hominids

Morphology

T.saginata T.solium

Size 4-8 m 2-4 m

Scolex 4 suckers4 suckers,

rostellum & hooklets

Mature proglottid

Ovary 2 lobes 3 lobes

Testes 300-400 150-200

Gravid proglottid: Uterine branches

15-30 7-12

The beef tapeworm (Living specimen)

The scolex of T. solium

The scolex of T. solium has four suckers and an armed-rostellum. The scolex of T. saginata looks similar but lacks hooks. These two species can be differentiated by counting the number of uterine branches in the proglottids; T. solium has between 7 to 13 per side, while T. saginata has 15 to 20.

The scolex of T. saginata

Taenia saginata, fresh specimen

Gravid proglottid of T. solium

Gravid proglottid of T. saginata

THE LARVAE

• Larva

Cysticercus bovis

Cysticercus cellulosae

Cysticercus racemose

– Ovoid, cystic, size = a bean

– Invaginated scolex and neck

T.solium: Cysticercus cellulosae with invaginated scolex

EGG

– Indistinguishable in two species– Ovoid– < Ascarid egg– Radically striated embryophore– Content: hexocanth embryo (oncosphere: 6

hooklets)

Taenia spp. egg Can not differentiate T. saginata from T. solium

Taenia spp. egg

Life cycle of Taenia saginataHumans are the only definitive hosts for Taenia saginata.

  The adult tapeworms (length: usually 5 m or less, but up to 25 m) reside in the small intestine, where they attach by their scolex.  They produce proglottids (each worm has 1,000 to 2,000 proglottids), which mature, become gravid, detach from the tapeworm, and migrate to the anus or are passed in the stool (approximately 6 per day).  The eggs contained in the gravid proglottids (80,000 to 100,000 eggs per proglottid) are released after the proglottid becomes free and are passed with the feces.  The eggs can survive for months to years in the environment.  Cattle and other herbivores become infected by ingesting vegetation contaminated with eggs (or proglottids).  In the animal's intestine, the eggs release the oncosphere, which evaginates, invades the intestinal wall and migrates to the striated muscles, where its develops into a cysticercus.  The cysticercus can survive for several years in the animal. Humans become infected by ingesting raw or undercooked infected meat.  In the human intestine, the cysticercus develops over 2 months into an adult tapeworm, which can survive for more than 30 years.

Life cycle of Taenia saginata

Life cycle of Taenia soliumThe life cycle of Taenia solium is similar to that of T. saginata.  The adults (length 2 to 7 m; less than 1,000 proglottids, which are less active than in T. saginata, and each with 50,000 eggs; longevity up to 25 years) develop not only in humans but also some other animal species (monkeys, hamsters).  The cysticercus develops not only in striated muscle, but also in the brain, liver, and other tissues of pigs and other animals, including humans.  Humans develop taeniasis when they ingest undercooked pork meat containing cysticerci.  They develop cysticercosis by ingesting T. solium eggs, either by ingestion of fecally contaminated food, or by autoinfection.  In the latter case, a human infected with adult T. solium ingests eggs produced by that tapeworm, either through fecal contamination or, more arguably, from proglottids carried into the stomach by reverse peristalsis.

T.saginata T.solium

D.H Human Human Human

I.H Cattle Swine Human

Habitation Small intestine Small intestineTissue(brain, eye,

skin etc.)

Infective stage Cysticercus bovisCysticercusCellulosae

Egg

Disease Taeniasis Taeniasis Cysticercosis

• Cysticercosis (Intrinsic or extrinsic auto-infection; Cross

infection due to T.solium egg only; Pathogenic factor:

cysticercus cellulosae)

– Symptoms vary with site & intensity of infection

– Clinical aspects: headache, dizziness, epilepsy,

blurred vision, subcutaneous nodule etc

Prevalece

• Most common infection of human nervous system by parasites.

• Most frequent preventable cause of epilepsy in developing world.

• Affects 50 million people worldwide. • 50,000 deaths in highly endemic places. • Interesting that a lot of developed countries also

are endemic for this disease – raw meat, but rate is going down due to stricter rules for meat inspection.

Epidemic factors

– Egg or gravid proglottid contamination of grass and soil

– Method of raising domestic animals– Unhygienic dinning habit of eating raw or

undercooked meat

.

TYPES OF CYSTS

Cysticercus cellulosae• Less virulent form• Small (<2cm), round, thin

walled• Lodges in the

parenchyma or the subarachnoid space

• Provokes only a minor inflammation

• Often remain silent

TYPES OF CYSTS

Cysticercus racemose • Large lobulated cysts with predilection

for basal cisterns• Causes cysticercotic arachnoiditis and

presents as meningitis• Causes obstruction of 4th ventricle and

resultant raised ICP and hydrocephalus

• Can cause occlusion of vessels and vasculits resulting in stroke

• Causes intense inflammatory reaction and seizures

MODE OF INFECTION

• HETEROINOCULATION– eggs may come from the environment

• INTERNAL AUTOINOCULATION– regurgitated from proglottids into the stomach

• EXTERNAL AUTOINOCULATION– from the fingers of an infected person Humans only acquire cysticercosis when they consume eggs

in food handled by people infected by adult T. solium or through the faecal-oral route

TARGET TISSUES

• Predilection for migration to eyes, CNS and striated muscles, probably due to high glycogen and glucose content of these tissues.

• CNS and Eye involvement is termed as Neurocysticercosis.

PRESENTATION

The manifold and diverse clinical presentation of NC is determined by

• Location of cysts• Size of cysts• Cyst load (number of cysts)• Host’s immune response

Anatomical Classification

• Parenchymal NC• Intraventricular NC• Meningeal NC• Spinal NC• Ocular NC

Nelson

CLINICAL SIGNS• The manifestations of NCC are polymorphic;

no symptom or sign is specific. • Acute symptomatic seizures are the most

common manifestation of human NCC; • the other clinical conditions include headache,

hydrocephalus, chronic meningitis, focal neurological defi cits, psychological disorders, dementia,ocular and spinal cysts

CLINICAL PRESENTATION

• Parenchymal NC– Seizures (87%)

• Simple partial with secondary generalization, generalized, complex partial or complex partial with secondary generalization

– Headache, nausea and vomiting– Stroke

• Hemiparesis • Focal neurologic deficits

– Frontal lobe involvement• Psychosis, dementia, parkinsonism, intellectual impairment

– Cerebellar Ataxia– Fulminant encephalitis in massive initial infection

CLINICAL PRESENTATION

• Intraventricular NC – 5- 10% of all cases– 4th ventricle most common site for obstruction – Cysts in lateral ventricles less likely to cause

obstruction– Hydrocephalus and acute, subacute or

intermittent signs of raised ICP without localizing signs

CLINICAL PRESENTATION

• Meningeal NC– Meningeal irritation resembling TBM– Raised ICP from oedema, inflammation and

presence of cyst obstructing flow of CSF

CLINICAL PRESENTATION

• Spinal NC– Spinal cord compression– Nerve root pain– Transverse myelitis– Arachnoiditis

• Ocular NC– Visual impairment (decreased visual acquity)– Scotoma, retinal detachment, iridocyclitis

DIAGNOSIS

• Stool Routine and Microscopy

• Fundoscopy• Biopsy and histopathology• CT with contrast• MRI• Serology

– EITB• sensitivity of 98% specificity

of 100% – ELISA in CSF

• sensitivity of 87% specificity of 95%

RADIOLOGICAL IMAGES

(A) Viable cyst with scolex

(B) degenerating cyst

(C) calcified cyst (non-contrast CT)

STAGES OF NC• Cystic or vesicular stage

• Cyst wall & scolex do not enhance • Cyst is viable & has a well defined, fluid-filled membrane contains only

one scolex.

• Colloid stage• Enhancing walls with perilesional oedema• Earliest stage in the involution of the cyst.• the fluid contents of the cyst become more turbid and the scolex begins

to degenerate.

• Necrotic, granular stage• Characterized by parasite necrosis and surrounding inflammation• Gives an appearance of an eosinophilic structure in which the bladder and

scolex are in various stages of disintegration• Oedema and/or necrosis of the surrounding neural tissue may be present

in some cases

• Fibro-calcified nodule• With time, fibrosis develops, progressively occupying the entire lesion

DIAGNOSTIC CRITERIA• Absolute criteria

– Demostration of cysticerci by histologic or microscopic examination of biopsy material– Visualization of the parasite in the eye by fundoscopy– Neuroradiologic demostration of cystic lesions containing a characteristic scolex

• Major criteria– Neuroradiologic lesions suggestive of NC– Demostration of antibodies to cysticerci in serum by enzyme linked

immunoelectrotransfer blot– Resolution of intracranial cystic lesions spontaneously or after therapy with albendazole

or praziquantel alone• Minor criteria

– Lesions compatible with NC detected by neuroimaging studies– Clinical manifestations suggestive of NC– Demonstration of antibodies to cysticerci or cysticercal antigen in CSF by ELISA– Evidence of cysticercosis outside the CNS (eg. Cigar shaped soft tissue calcification)

• Epidemiologic criteria– Residence in a cysticercosis-endemic area– Frequent travel to a cysticercosis- endemic area– Household contact with an individual infected with T. solium

DIAGNOSTIC CRITERIA

• Definitive– 1 absolute– 2 major– 1 major + 2 minor + 1 epidemiological

• Probable– 1 major + 2 minor– 1 major + 1 minor + 1 epidemiological– 3 minor + 1 epidemiological

• Possible– 1 major– 2 minor– 1 minor + 1 epidemiological

SUGGESTED DIAGNOSTIC CRITERIA

• Absolute criteria• Histopathological demostration of the parasite in the tissues obtained from the

biopsy of a brain or spinal cord lesion• Multiple cystic lesions with or without scolex on CT or MRI

• Major Criteria• Lesion highly suggestive of NC in neuroimaging studies• Spontaneous resolution or eventual calcification• Positive serum EITB assay for the detection of antibodies against T. solium

• Minor criteria• Presence of a characteristic clinical picture• Positive CSF ELISA• Cysticercosis outside the CNS• Aggravation of existing symptoms or appearance of a new symptom following

anticysticercal therapy• Diagnosis with caution

• Old age• Patients with pre existing systemic tuberculosis or malignancy• HIV infection• Grossly abnormal neurological examination

Garg

DDX: Tuberculoma Versus Cysticercus Granuloma

Cysticercus Granuloma• Round in shape• Cystic• 20mm or less with ring

enhancement or visible scolex

• Cerebral edema not enough to produce midline shift or focal neurological deficit

Tuberculoma• Irregular in shape• Solid• Greater than 20mm• Associated with severe

perifocal edema and focal neurological deficit

Target lesions: Lesions with central nidus of calcification or a dot enhancement

TREATMENT

• Praziquantel three doses of 25-30 mg/kg at 2-hour intervals on a single day equally effective to the 50mg/kg 8 hourly dose for 15 days.

• Albendazole 15mg/kg/day in 2 divided doses for 1 week equally effective to the 15 mg/kg/day 12 hrly for a 1-month period.

Surgery restricted to:

• Placement of ventriculo-peritoneal shunts for hydrocephalus

• Excision of single big cysts causing mass effect

• Endoscopical excision of intraventricular parasites.

• Unfortunately shunts are frequently occluded by the high protein content and debris in the CSF of patients with extraparenchymal neurocysticercosis, requiring multiple revisions.

• Deaths due to shunt dysfunction may occur in up to 50% of cases, mainly in the initial 1–2 years after placement.

PREVENTION.• Changing domestic pig-raising practices. Keeping/raising pigs that have access to human

faeces Lack of latrines or latrines accessible by pigs Eating undercooked or raw pork • Mass chemotherapy of porcine cysticercosis. • Community health education. • S3PVAC Porcine vaccine against cysticercosis is

available (pig farmers cannot afford it though) – eliminates infection.

INDIAN SCENARIO• Cysticercosis has been designated as a “biological marker”of the

social and economic development of a community• Recent Indian studies using neuroimaging techniques suggest that

the disease burden in India surpasses many other developing countries

• All the biological markers for transmission of T. solium taeniasis and cysticercosis exist in India

• Disease is under reported in India because due attentionhas not been given to this neglected disease and systematic population-based studies are lacking

• There are great disparities within the country in geography, ethnicity, religious rituals, income, food habits, personal hygiene, level of education and standards of living, which are likely to influence the disease burden.

• There are wide variations in the frequency of cysticercosis in India

Human Cysticercosis in India

• There are only few reports from the State of Kerala,where the level of education and standards of hygiene are high, and from Jammu and Kashmir, a Muslim majority State due to prohibition of pork consumption by religion

• Before the era of CT scan and magnetic resonance imaging (MRI),National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore reported diagnosis of NCC in 2% of an unselected series of epileptics (Mani et al 1974)

• At atertiary referral centre in New Delhi, NCC constituted 2.5%of all intracranial space occupying lesions (Wani et al 1981).

• With the availability of CT and MRI, the proportion of NCC in seizure disorders dramatically increased. Sawhney et al (1996) reported cerebral cysticercosis in 31% of patientsin whom CT was done.

• In a community survey of 50,617 individuals from South India, the prevalence of active epilepsy was 3.83 per 1000 and NCC was detected in 28.4% of them by CT (Rajshekhar et al 2006).

• Cysticercosis appears to be more prevalent in the northern States Bihar, Uttar Pradesh through Punjab. In a recent study based on 30 cluster sampling approach suggested by WHO in the rural pig farming community of Mohanlalganj block, Lucknow district, Uttar Pradesh, the prevalence of taeniasis was 18.6 (Prasad et al 2007).

• In the same community active epilepsy was identifi ed and clinically confi rmed in 5.8% of the populations during door to door survey and 48.3% of them fulfilled either defi nitive or probable diagnostic criteria of NCC. Epilepsy in the family and no separate place for pig were identifi ed as risk factors for NCC clustering. (Prasadet al 2008)

• In a study of 156 histologically proven cases of cysticercosis from Patiala, Punjab, 88% patients presented with solitary lesion and the most frequent site being the upper arm, chest wall, eye, abdomen wall and neck (Saigal et al 1984)

• The prevalence of taeniasis ranged from 0.5-2% in hospitalized patients in northern India, 12–15% in labour colonies where pigs are raised (Mahajan et al 1982).

• The treatment gap in rural India is above 90% (Prasad et al 2008b) and the probable reasons for such high gap are socioeconomic, lack of knowledge and medical facilities, social prejudice to modern medicine and faith in alternative treatment modalities.

Cysticercosis in Swine

• Cysticercosis also appears to be widespread in swine in India. In and around Chandigarh, 8-10% of the pigs slaughtered had cysticerci in their muscles and around 0.5% of the pigs reared in Government farms were found to be infected (Mahajan et al 1982).

• Another survey in slaughter houses of Kolkata (West Bengal) revealed cysticercosis in muscles of 7% of the slaughtered pigs (Ratnam et al 1983).

• Prasad et al (2002) reported a high frequency of cysticercosis (26%) in swine from Mohanlalganj block of Lucknow district in the State of Uttar Pradesh and 40% ofthem had cysticerci in the brain.

Neurocysticercosis-more than a neglected disease (Nash et al., 2013)

• Neurocysticercosis (NCC) is the most common cause of adult-acquired epilepsy worldwide and one the most frequent parasitic infections associated with chronic morbidity in the United States.

• Despite its importance worldwide morbidity due to NCC is underappreciated and research is underfunded, and therefore researchers are unable to capitalize on recent advances that hold great promise to prevent millions of cases of epilepsy and to effectively treat viable brain infections.

• By conservative estimates, greater than 5 million cases of epilepsy worldwide, which are all preventable, are caused by NCC.

• The study of NCC is inherently difficult. The life cycle is near impossible to maintain in the laboratory, and for practical purposes purposes most basic research cannot be performed in developed, non-endemic countries. The high cost of the logistics to establish and maintain the stages of the life cycle required for basic experiments is compounded by the difficult challenge of obtaining financial support for a neglected disease.

• It is easy to forget that a few decades ago the diagnosis of NCC was made infrequently, medical treatments were unavailable, and its role as a primary cause of adult onset epilepsy unknown

• Controlled human treatment trials and observational studies are difficult to conduct because of their cost, need for frequent imaging, and requirement for long periods of follow up.

Areas of study 1) Determine the extent and burden of disease worldwide. 2) Understand that great strides can be made with relatively

few resources, for example: a. Development of methods to test for new and effective

drugs. b. Use of existing, licensed immunomodulators to control

treatment- induced inflammation and damaging inflammation in parenchymal and subarachnoid disease.

c. Effective use of vaccination in pigs.3) Boost support for the relatively few programs devoted to

NCC.

4) In the United States, realize that health care and research is hindered because those with disease have the least access to health care; they are commonly undocumented Central and South American immigrants. Often, the most minimal care and testing is allowed or given.

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