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

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 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

Hetero Infection – eggs liberated from disintegrating gravid proglottides passed by one individual get into the mouth of another and are swallowed 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

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

Clinical Presentation  Epileptogenesis in Neurocysticercosis  Generally, patients would a partial-onset seizures with or without secondary generalization  New onset seizures are commonly associated with active cysts rather than calcified granuloma.  Cysts that are active and undergoing degeneration are the most epileptogenic.  It can be attributed to several factors:  Inflammation  Gliosis  Genetics  Predilection for the cyst to travel to frontal and temporal lobes. 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

Clinical Presentation  Seizure recurrence is high after a first acute symptomatic seizure due to NC, but this seems related to persistence of active brain lesions.  Patients with NC should receive anti-seizure medications until the acute lesion clears on CT.  There is no correlation between treatment with antihelminthic agents and seizure recurrence. Prognosis for seizure recurrence in patients with newly diagnosed neurocysticercosis Arturo Carpio, MD and W. Allen Hauser, MD From the School of Medicine and Research Institute, University of Cuenca, Ecuador; and G.H. Sergievsk Neurology 2002;59: © 2002 American Academy of Neurology y Center, College of Physicians and Surgeons, Columbia University, New York, NY.American Academy of Neurology

Stages of Neurocysticercosis  Vesicular stage  Colloid stage  Granular-nodular stage  Calcified Granulomas

“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.

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.

Vesicular Stage  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. 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

Colloidal Stage  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. 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

Nodular-Granular  The vesicle shrinks, and become semisolid. With further deterioration it forms a nodule and progressively replaced by granulomatous tissue.

Calcified Granulomas  Mineralization and resorption process occurs that lodges permanently in the CNS.  Noncontrast CT scan shows a rounded, homogeneous hyperdense area and showing no enhancement with contrast medium.

VESICULARCOLLOIDALNODULAR- GRANULAR CALCIFIED CT 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)

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

Immunologic Assay  Enzyme ImmunoBlot 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.

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.

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.

Definitive diagnosis of extra-neural cysticercosis will require one of the following: a)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.

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.

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.

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. GUIDELINES FOR USE OF ANTIPARASITIC TREATMENT IN NEUROCYSTICERCOSIS

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