1. DISCUSSION Neurocysticercosis

2. CYSTICERCOSIS
Is a parasitic infection that results from ingestion of eggs from the adult tapeworm, Taenia solium (T.solium).
When it involves the central nervous system, it is called Neurocysticercosis – which is the most common parasitic infection of the brain and a leading cause of epilepsy in the developing world.
Neurocysticercosis; Christopher M. DeGiorgio, MD; Marco T. Medina, MD, Reyna Duron, MD, Chi ZEE, MD; Susan Pietsch Escueta, MPH.
Epilepsy Currents Vol 4, No.3 (May/June) 2004 pp , Blackwell Publishing Inc. American Epilepsy Society

3. Etiology TAENIA SOLIUM (pork tapeworm)
*the parasite producing taeniasis solium or pork tapeworm infection
Taeniasis occurs after ingestion of improperly cooked pork and tapeworm carriers disseminate eggs in their feces
The adult tapeworm generally resides in the upper jejunum. The scolex attaches by both sucking disks and two rows of hooklets. Often only one adult worm is present, but that worm may live for years. The tapeworm, usually ~3 m in length, may have as many as 1000 proglottids, each of which produces up to 50,000 eggs. Groups of 3–5 proglottids are generally released and excreted into the feces, and the eggs in these proglottids are infective for both humans and animals. The eggs may survive in the environment for several months.
Taenia solium Cysticercosis Hotspots Surrounding Tapeworm Carriers: Clustering on Human Seroprevalence but Not on SeizuresLescano AG, Garcia HH, Gilman RH, Gavidia CM, Tsang VCW, et al. (2009) Taenia solium Cysticercosis Hotspots Surrounding Tapeworm Carriers:
Clustering on Human Seroprevalence but Not on Seizures. PLoS Negl Trop Dis 3(1): e371. doi: /journal.pntd

4. After ingestion of eggs by the pig intermediate host, the larvae are activated, escape the egg, penetrate the intestinal wall, and are carried to many tissues, with a predilection for striated muscle of the neck, tongue, and trunk. Within 60–90 days, the encysted larval stage develops. These cysticerci can survive for months to years. By ingesting undercooked pork containing cysticerci, humans acquire infections that lead to intestinal tapeworms. Infections that cause human cysticercosis follow the ingestion of T. solium eggs, usually from close contact with a tapeworm carrier. Autoinfection may occur if an individual with an egg-producing tapeworm ingests eggs derived from his or her own feces.

6. External autoinfection – eggs maybe
transferred from anus to mouth or unclean fingertips of an individual who has an intestinal infection with Taeniasis solium
Internal autoinfections – gravid proglottids in an individual harboring the adult Taenia solium may become detached from the main strobila or regurgitated into the stomach and then return to duodenal canal where they disintegrate and liberate ripened eggs
Hetero Infection – eggs liberated from disintegrating gravid proglottides passed by one individual get into the mouth of another and are swallowed

7. Clinical Presentation
05/25/09
Clinical Presentation
Brain Parenchyma
New onset partial seizure with or without secondary generalization (focal or multufocal, possibly intractable)‏
Subarachnoid or Ventricular Space
Increased ICP
Pseudotumor (diffuse parenchymal involvement)
Obstructive hydrocephalus (intraventricular cysts, racemmeningeal cysts)‏
Intracranial space occupation (parenchymal cysts)
Meningoencephalitis
Basal arachnoiditis
Psychiatric disorders, including dementia
Spine
can mimic presentation of intraspinal tumor

8. Stages of Neurocysticercosis
05/25/09
Stages of Neurocysticercosis
Vesicular stage
Colloid stage
Granular-nodular stage
Calcified Granulomas
The host may tolerate the worm as long as the embryo is alive. Viable cysticerci are associated with minimal inflammation (vesicular stage). The worm usually dies 2-6 years after infection, and the disintegration of the parasite triggers a vigorous tissue reaction. An inflammatory response to the degenerating cyst results in severe symptoms. As the cysticerci lose the ability to control the host's immune response, the cyst wall becomes infiltrated and is surrounded by predominantly mononuclear cells. Inflammatory cells enter the cyst fluid (colloid stage). As the host's immune response progresses, fibrosis encompasses the cysticercus, with concomitant collapse of the cyst cavity (granular- nodular stage). The dead parasite decays into eosinophilic desiccated material.
The final stage is a calcified nodule, which presumably forms as a result of dystrophic calcification of the necrotic larva (calcific stage). The various pathologic states that may be seen in NCC include the following: (1) meningoencephalitis, (2) granulomatous meningitis, (3) focal granuloma, (4) focal or diffuse multiple cysts, (5) hydrocephalus, (6) intraventricular cysts, (7) ependymitis, and (8) arteritis.

9. DIAGNOSIS

10. “The diagnosis of neurocysticercosis is difficult because clinical manifestations are nonspecific, most neuroimaging findings are not pathognomonic, and some serologic tests have low sensitivity and specificity.” “ Differential diagnosis between cysticercosis and other parasitic diseases may be difficult on clinical grounds. However, epidemiological data as well as evidence provided by neuroimaging studies and highly specific immune diagnostic tests usually provide useful diagnostic clues.”
Current Consensus Guidelines for Treatment of Neurocysticercosis; Hector H. García et.al.; CLINICAL MICROBIOLOGY REVIEWS, Oct. 2002, p. 747–756 Vol. 15, No. 4; /02/$ DOI: /CMR – ; Copyright © 2002, American Society for Microbiology.

11. Diagnosis of neurocysticercosis stems from suspicions that arises from the clinical manifestations of the disease
Most useful diagnostic test and the primary diagnostic criteria is neuroimaging
1. Contrast CT
2. MRI
Useful in the evolution of cysticercus in the parenchyma of brain.
1. Contrast CT – picks up calcified cyst
2. MRI - If CT scan not conclusive.
MRI is better for identifying cystic lesions and enhancement.

12. 05/25/09
When the cysticerci first lodge in the brain, they frequently cause little in the way of an inflammatory response. As the cysticercal cyst degenerates, it elicits an inflammatory response that may present clinically as a seizure. Eventually the cyst dies, a process that may take a several years and is typically associated with resolution of the inflammatory response and, often, abatement of seizures.
Primary toxoplasma infection is often asymptomatic. However, during this phase parasites may spread to the CNS, where they became latent. Reactivation of CNS infection is almost exclusively associated with immunocompromised hosts, particularly those with HIV infection. During this phase patient present with headache, fever, seizures and focal neurological deficits. 12

13. Vesicular Phase
The larva lives inside a translucent liquid-filled cystic structure surrounded by a thin membrane, where it can remain viable from a few months to several years.
Has minimal enhancement which is due to little or no host immune response.
At this stage, imaging may show may show a high intensity, 2-4 mm mural nodule, depicting the scolex in the interior of some parenchymal vesicular cysts. This picture could be considered pathognomonic of cysticercosis, and it corresponds to the active parenchymal form.
Neurocysticercosis; Christopher M. DeGiorgio, MD; Marco T. Medina, MD, Reyna Duron, MD, Chi ZEE, MD; Susan Pietsch Escueta, MPH.
Epilepsy Currents Vol 4, No.3 (May/June) 2004 pp , Blackwell Publishing Inc. American Epilepsy Society

14. Colloidal
As the cyst degenerates, fluid from the larva cyst leaks into the parenchyma, generating a strong immune response characterized by enhancement on CT and MRI scans
The vesicular fluid takes on a gelatinous colloidal aspect, and the wall thickens.
Host-immune system starts to react to the parasite
Parasite begins to show degenerative changes
Neurocysticercosis; Christopher M. DeGiorgio, MD; Marco T. Medina, MD, Reyna Duron, MD, Chi ZEE, MD; Susan Pietsch Escueta, MPH.
Epilepsy Currents Vol 4, No.3 (May/June) 2004 pp , Blackwell Publishing Inc. American Epilepsy Society

15. Nodular-Granular
The vesicle tends to shrink, and become semisolid. With further deterioration it forms a nodule and progressively replaced by granulomatous tissue.
These 2 consecutive phases correspond to an intermediate stage named transitional form, inasmuch as the cysticercus has entered into a degenerative process. Although these pathologic changes generally are associated with symptoms (eg, seizures, headaches), some patients with these changes remain asymptomatic.

16. Calcified Granulomas
Mineralization and resorption process occurs that lodges permanently in the CNS.
Noncontrast CT scan shows a rounded, homogeneous hyperdense area showing no enhancement with contrast medium.
This phase corresponds to the inactive parenchymal form of NC.

17. CT MRI VESICULAR COLLOIDAL NODULAR-GRANULAR CALCIFIED
circumscribed, rounded, hypodense areas, ave. size 10 mm, range 4-20 mm, no enhancement
annular enhancement surrounded by irregular perilesional edema
diffuse hypodense area with irregular borders
(non-contrast)
a small, hyperdense, rounded, nodular image surrounded by edema (ff contrast)
rounded, homogeneous hyperdense area showing no enhancement with contrast medium
MRI
CSF-like intensity signal on all sequences, with no surrounding high signal on T2-weighted images.
higher signal than the adjacent brain with thick-ring enhancement (T1)
a low-ring signal surrounded by high signal lesion (T2)
change in the signal from the cyst fluid (T2)
Vesicular - pathognomonic of cysticercosis, and it corresponds to the active parenchymal form of NC.

18. Brain imaging studies demonstrating the 4 stages of parenchymal neurocysticercosis
Neurocysticercosis; Christopher M. DeGiorgio, MD; Marco T. Medina, MD, Reyna Duron, MD, Chi ZEE, MD; Susan Pietsch Escueta, MPH.
Epilepsy Currents Vol 4, No.3 (May/June) 2004 pp , Blackwell Publishing Inc. American Epilepsy Society

19. Immunologic Assay Enzyme ImmunoBlot ELISA
The current serological assay of choice for the diagnosis of neurocysticercosis
CDC's immunoblot is based on detection of antibody to one or more of 7 lentil-lectin purified structural glycoprotein antigens from the larval cysts of T. solium.
It is 100% specific.
ELISA
Lack of specificity has been a major problem because of cross-reacting components in crude antigens derived from cysticerci.
These components react with antibodies specific for other helminthic infections, especially echinococcosis and filariasis. 
No serum samples from patients with other microbial infections react with any of the T. solium-specific antigens. 
Cumulative clinical experience has confirmed that in patients with multiple (more than two) lesions, the test has more than 95% sensitivity.
Assays employing crude antigens for the detection of antibody are not reliable for the identification of this disease
CDC's immunoblot assay with purified Taenia solium antigens has been acknowledged by the World Health Organization and the Pan American Health Organization as the immunodiagnostic test of choice for confirming a clinical and radiologic presumptive diagnosis of neurocysticercosis. 

20. DIAGNOSTIC CRITERIA for NEUROCYSTICERCOSIS
Absolute criteria
Histologic demonstration of parasite
Direct visualization of parasite by fundoscopic examination.
Evidence of cystic lesions showing scolex on CT/MRI
 Major Criteria
Lesions suggestive of neurocysticercosis on CT or MRI
Positive serum EITB (Enzyme Immunoblot Assay)
Resolution of cyst after therapy.
Spontaneous resolution of single enhancing lesions.
Minor criteria
Lesions compatible with neurocysticercosis on CT/MRI
Suggestive clinical features
Positive CSF ELISA
Cysticercosis outside CNS
Epidemiologic
Evidence of household contact with T. solium infection
Individuals coming from or living in endemic area
History of frequent travel to disease-endemic area
Current Consensus Guidelines for Treatment of Neurocysticercosis; Hector H. García et.al.; CLINICAL MICROBIOLOGY REVIEWS, Oct. 2002, p. 747–756 Vol. 15, No. 4; /02/$ DOI: /CMR – ; Copyright © 2002, American Society for Microbiology.

21. 2 major + 1 minor + 1 epidemiologic
For DIAGNOSTIC CERTAINTY:
DEFINITIVE
1 absolute
2 major + 1 minor + 1 epidemiologic
PROBABLE
1 major + 2 minor
1 major + 1 minor + 1 epidemiologic
3 minor + 1 epidemiologic
Current Consensus Guidelines for Treatment of Neurocysticercosis; Hector H. García et.al.; CLINICAL MICROBIOLOGY REVIEWS, Oct. 2002, p. 747–756 Vol. 15, No. 4; /02/$ DOI: /CMR – ; Copyright © 2002, American Society for Microbiology.

22. Definitive diagnosis of extra-neural cysticercosis will require one of the following:
histopathological demonstration of parasite from excisional biopsy of a subcutaneous nodule. Demonstration of larval parts (hooks, suckers etc.) by fine needle aspiration cytology may provide a satisfactory alternative to open biopsy
b) plain X-ray films showing multiple "cigar-shaped calcifications in the arm, thigh and calf muscles
c) direct visualization of a cysticercosis larva in the anterior chamber of the eye with ultrasonography.

23. TREATMENT
Therapeutic measures include antiparasitic drugs, surgery and symptomatic medications.
Praziquantel and Albendazole are effective anti-parasitic drugs against T. solium cysticerci.
Praziquantel
As low as 5-10mkd or as high as 50-75mkd
Albendazole
Used as 15mg/kg/day
The initial length of therapy was 1 month, later reduced to 15 days and 1 week. Around
60-85% of parenchymal brain cyst are killed after standard dose treatment.
Current Consensus Guidelines for Treatment of Neurocysticercosis; Hector H. García et.al.; CLINICAL MICROBIOLOGY REVIEWS, Oct. 2002, p. 747–756 Vol. 15, No. 4; /02/$ DOI: /CMR – ; Copyright © 2002, American Society for Microbiology.

24. GUIDELINES FOR USE OF ANTIPARASITIC TREATMENT IN NEUROCYSTICERCOSIS
Current Consensus Guidelines for Treatment of Neurocysticercosis; Hector H. García et.al.; CLINICAL MICROBIOLOGY REVIEWS, Oct. 2002, p. 747–756 Vol. 15, No. 4; /02/$ DOI: /CMR – ; Copyright © 2002, American Society for Microbiology.

25. GUIDELINES FOR USE OF ANTIPARASITIC TREATMENT IN NEUROCYSTICERCOSIS
Current Consensus Guidelines for Treatment of Neurocysticercosis; Hector H. García et.al.; CLINICAL MICROBIOLOGY REVIEWS, Oct. 2002, p. 747–756 Vol. 15, No. 4; /02/$ DOI: /CMR – ; Copyright © 2002, American Society for Microbiology.

26. A critical review of the available data from comparative trials suggests that albendazole is more effective than praziquantel regarding clinically important outcomes in patients with neurocysticercosis
Matthaiou DK, Panos G, Adamidi ES, Falagas ME (2008) Albendazole versus Praziquantel in the Treatment of Neurocysticercosis: A Meta-analysis of Comparative Trials. PLoS Negl Trop Dis 2(3): e194. doi: /journal.pntd

27. PANEL CONSENSUS—GENERAL CONCEPTS
(i) Treatment must be individualized in terms of number and location of lesions, as well as based on the viability of the parasites within the nervous system
(ii) Growth of a parenchymal cysticercus is not a common event and may be life-threatening. A growing parasite deserves active management.
(iii) The priority is to manage the hypertension problem before considering any other form of therapy. Antiparasitic drug treatment is never the main priority in the setting of elevated intracranial pressure
(iv) Antiepileptic drugs are the principal therapy for seizures in neurocysticercosis. However, after resolution of the parasitic infection with normalization of imaging studies, most patients who are seizure-free can eventually discontinue antiepileptic drugs.
Current Consensus Guidelines for Treatment of Neurocysticercosis; Hector H. García et.al.; CLINICAL MICROBIOLOGY REVIEWS, Oct. 2002, p. 747–756 Vol. 15, No. 4; /02/$ DOI: /CMR – ; Copyright © 2002, American Society for Microbiology.

29. THANK YOU!
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30. When only one cyst is seen in the transitional phase, it corresponds to the so-called "single enhancing lesion on CT" (SECTL), signifying a special syndrome.