Njns jan 2007.pmd

Original Article
Nepal Journal of Neuroscience 3:80-84, 2007
Neurocysticercosis: A Review
Amit Agarawal, MCh
Department of Surgery
Neurocysticercosis (NCC) is the most common parasitic disease of the central nervous system and is a major cause of epilepsy and neurological morbidity in endemic areas ofthe world. International travel and immigration are bringing Guru Prasad Khanal, MS
neuro-cysticercosis to areas where it is not endemic and Department of OrthopedicsB.P.Koirala Institute of Health Sciences incidence of NCC is increasing in the developed countries also. The diagnosis of neurocysticercosis is difficult becauseclinical manifestations are nonspeciûc, most neuroimaging Address for correspodence:
ûndings are not pathognomonic, and some serologic tests have low sensitivity and speciûcity. The treatment of Department of SurgeryB.P.Koirala Institute of Health Sciences neurocysticercosis is controversial and depends on the clinical and neuroimaging features, as well as the extent and severity of the associated inflammatory reaction.
Albendazole and praziquantel are the principal antiparasitic Received, October 10, 2006
drugs used to treat neurocysticercosis. However, better Accepted, November 25, 2006
understanding of the mechanisms of neurocysticercosis; the
life cycle of T. solium, and better sanitation habits of the
population are needed to develop appropriate intervention
and prevention programs. In this article we review the
current concepts in the management of neurocysticercosis.
Key Words: Cysticercosis, Neurocysticercosis, Taenia
solium
Neurocysticercosis (NCC) is the most common that are the source of infection with the larval stage, or parasitic disease of the central nervous system.
cysticercosis. The natural intermediate host is the pig, NCC is a major cause of epilepsy and neurological harboring larval cysts anywhere in its body. Humans morbidity in endemic areas of the world. 1,2,3 It is rare in become infected with cysts by accidental ingestion of T.
non-endemic areas, so a high degree of awareness is solium infective eggs by fecal-oral contamination. After necessary for diagnosis. It is often benign and lesions can ingestion of Taenia eggs containing infective onco-spheres, resolve within months. 2 However in less developed the parasites become established in the tissues as larval countries the diagnosis of neurocysticercosis is frequently cysts and reach their mature size in about 3 months. 7,8 difficult because several other prevalent neurological Oncospheres cross the gastrointestinal tract and migrate disorders can present with a similar clinical and via the vascular system to the brain, muscle, eyes, and neuroimaging picture.1 The preva-lence of other structures. Once in the brain, the larval cysts neurocysticercosis in some of these developing coun-tries (cysticerci) initially generate a minimal immune response exceeds 10%, 4,5 where it accounts for up to 50% of cases of and may remain in the brain as viable cysts for years. 9 The late-onset epilepsy. 6 International travel and immigration infection burden varies from a single lesion to several are bringing neuro-cysticercosis to areas where it is not hundreds, and lesions may range in size from a few endemic. In this article we review the current concepts in millimeters to several centimeters. 10, 11, 12 Laboratory studies the management of neurocysticercosis.
and information from other cestodes suggest that viablecysts ac-tively modulate the host’s immune system to evade Etio-pathology
destruction by it. 13, 14 Prevalence of cysticercosis and Taenia solium is a two-host zoonotic cestode. The adult taeniasis may be related with gender, age, residential area stage is a 2-to 4-m-long tapeworm that lives in the small as well as pork consumption and contact with the people intestine of humans. No other ûnal hosts are known for T.
who infected with the adult worm. In addition, higher levels solium tape-worms in nature. As in all cestodes, the gravid of human infection are closely associated to porcine proglottids at the terminal end of the worm are full of eggs cysticercosis and inadequate sanitary infrastructure. 15 Nepal Journal of Neuroscience, Volume 4, Number 1, 2007 Neurocysticercosis
Epileptogenesis in Neurocysticercosis
in the Sylvian ûssure. Cysticercotic encephalitis is a rare The pathophysiology of the seizures due to NCC is not form of the disease in which patients have numerous completely understood yet. In active and transitional forms, inûamed cysticerci, leading to diffuse, severe cerebral seizures may be the consequence of compression or edema. 26,27 Headache usually indicates the presence of inflammatory reaction. In inactive form, perilesional gliosis hy-drocephalus, meningitis, or increased intracranial is probably the cause of the seizures. Chronic inflam-matory pressure. When hydrocephalus is present, the use of reaction sometimes takes several years to di-sappear and it antiparasitic drugs is relatively contraindicated, unless a may have an important role in the pathophysiology of focal shunt is placed before ad-ministration. The mortality rate epilepsy in NCC. 16,17 Generally, patients with of patients with hydrocephalus or increased intracranial neurocysticercosis have partial-onset seizures with or pressure is higher than the mortality rate of patients with without secondary generalization. 6 At the time of a ûrst seizure, most patients have an active cyst—either avesicular cyst or a colloidal cyst. 17 New-onset seizures are Extraparenchymal Neurocysticercosis
commonly associated with active cysts rather than calciûed Extraparenchymal infection may cause hydrocephalus by granulomas. 17, 18 Chronic epilepsy is usually associated mechanical obstruction of the ventricles or the basal with calciûed granulomas. 6, 17,18,19,20 Cysts that are active cisterns, either by the cysts them-selves or by an and undergoing degeneration (colloidal cysts) are the most inûammatory reaction (ependymitis and/or arachnoiditis).
epileptogenic. Cysts degenerate fastest within 6 to 12 The so-called racemose variety occurs in the ventricles or months after initial presentation. 18 Seizure-recurrence rates basal cisterns and is characterized by abnormal growth of also increase during the same period, because of the cystic membranes with degeneration of the parasite’s head conversion from vesicular cysts to colloidal cysts. 18 (scolex). 26,27 Extraparenchymal neurocysticercosis includescysticerci in the ventricles and basal cisterns (racemose Clinical Features
cysticercosis. Since the cyst membrane is thin and the ûuid In most patients, neurocysticercosis seems to produce is isodense with the cerebrospinal ûuid, uninûamed symp-toms years after the initial invasion of the nervous extraparenchymal cys-ticerci are usually not visible on CT system by the parasite, by either inûammation around the and may only reveal subtle, indirect ûndings on MRI. Scans parasite, mass effect, or residual scarring. 21,22 There is a may reveal hydrocephalus without noticeable cysts, clear associa-tion between inûammation around one or more ependymitis, distorted basal cisterns, or basal meningitis.
29,30,31 cysts and de-velopment of symptoms, especially withregard to seizures. 14 Symptomatic disease results almostexclusively from the in-vasion of the nervous system Diagnosis
(neurocysticercosis) and the eye and is clearly different in The diagnosis of neurocysticercosis is difûcult because parenchymal neurocysticercosis and extraparenchymal clin-ical manifestations are nonspeciûc, most neuroimaging ûnd-ings are not pathognomonic, and some serologic testshave low sensitivity and speciûcity. 32,33 NCC is diagnosed Parenchymal Neurocysticercosis
largely by characteristic neuroimaging findings such as Clinical manifestation of the disease is highly computerized tomography (CT) and magnetic resonance pleiomorphic and non-specific according to the number (MR). Since the number, size and location of the infected and location of worms infected in the CNS as well as the cysts and stage of infections are variable in many patients, stage of the infection. 23 The usual presentation of however, imaging diagnosis is often confusing and parenchymal neurocysticercosis is with seizures, which can inconclusive in some extents. In such cases, detection of be controlled with antiepileptic drug therapy. Occasionally, specific antibodies circulated in the sera or cerebrospinal the cysts may grow and produce a mass effect. 24,25,26 Viable fluids (CSF) by enzyme linked immunosorbent assay cysts are 10 to 20 mm in diameter, thin-walled sacks ûlled (ELISA) or by immunoblot is helpful to confirm or to exclude with clear cyst ûuid. On imaging studies, the wall is not the diagnosis. In addition, serological test is useful for visible and the ûuid is isodense with the cerebrospinal epidemiological survey in a large scale in endemic areas ûuid. There is little or no evidence of perilesional due to its easy applicability and high reproducibility. 25 inûammation, and they do not en-hance with contrast media Cystic hydatid disease almost always appears on CT/MRI on neuroimaging. As the parasite loses the ability to control as a single, large, spherical, and nonenhancing intracranial the host immune response, an inûammatory process begins.
cyst. This is a very rare form of presentation of T. solium Initially, the cysts show slight pericystic contrast cysticercosis. Also, the current assay of choice, enhancement. Later they become markedly inûamed and immunoblot, does not cross-react with echinococco-sis.
edematous and appear as ring-like or nodular areas of Other condition that may resemble T. solium cysticercosis enhancement after the injection of contrast. This phase from the clinical and neuroimaging points of view is has been called “granulomatous cysticer-cosis, “cysticerci coenuro-sis, an extremely rare condition caused by the in encephalitic phase,” or “enhancing le-sions.” Finally, the cyst is processed by the cellular response, and its Neuroimaging has attained enormous progress du-ring remnants either are not detectable by imaging or be-come last decade. Despite that, CT is very helpful in NC because calciûed lesions. “Giant” cysts, measuring more than 50 it is a safe, precise and noninvasive method with more than mm in diameter, are occasionally found, located pri-marily 95% accuracy to define number, localization and Nepal Journal of Neuroscience, Volume 4, Number 1, 2007 Agrawal & Khanal
evolutionary stage of the parasite, especially in the Prognosis
parenchymal form of the disease. 34 In developing countries In adults and children ûrst seen with new-onset where MRI machines are not always available, and seizures and active cysts, seizure recurrence rates at 4 considering the fact that calcifications are the main years are as high as 49%. 18 After a second seizure, the radiological finding in NC, CT is still the most performed estimated risk of recur-rence is 68% at 6 years. 18 Prognosis is best for those patients in whom imaging studiesnormalize. The recurrence rate for those patients with Management
persisting, active cysts (61%) is more than double the The treatment of neurocysticercosis is controversial and rate of patients with normal imaging (22%). 18 Seizure depends on the clinical and neuroimaging features, as recurrence is reduced in patients who initially have well as the extent and severity of the associated calciûcations rather than active cysts. 17,19,20 Del Brutto et inflammatory reaction. 35 Albendazole and praziquantel are al. found that patients ûrst seen with new-onset seizures the principal antipara-sitic drugs used to treat and calciûcations fared better than those with active cysts: neurocysticercosis. 18,36,37,38,39 Whether and when 100% with calciûcations were seizure free at 2 years, antiparasitic drugs should be administered is compared with 83% with active cysts. 17 Dur´on et al.
controversial. Data from open-label trials suggest that similarly found that among 25 patients initially seen with prazi-quantel and albendazole reduce the number of cysts calciûcations, seizures remitted in 62.8%. 19 Basal and fre-quency of seizures. 38,40,41,42 In a seminal study, subarachnoidal cysticercosis and racemose disease of Vasquez and Sotelo found that seizure-free rates at 3 years, sylvian fissure may behave aggressively producing for those offered antiparasitic therapy, were signiûcantly intracranial hypertension, obstructive hydrocephalus, higher than those of a nonrandomized control group (94% chronic arachnoiditis, vasculitis, and cerebral infarctions.
seizure free). 42 This ûnding is supported by data from Del 44 Subarachnoidal cysticercosis may have a chronic course Brutto et al., who found that 83% of those individuals and a poor prognosis, and is still treated surgically. 45 Pre- who received antiparasitic treatment became seizure free, treatment with corticosteroids reduces the risk of com-pared with only 26% of those patients who did not complications secondary to destruction of cysticerci. 44,46 receive treatment. 17 Some authors suggest thatantiparasitic treatment might be counterproductive and Prevention Strategies
expose patients to increased risk.37 The risks of Cysticercosis is placed in the middle of sociocultural antiparasitic therapy include gastrointestinal side effects, studies related to poverty and ignorance. 47 Wandering acute seizures, increased intracranial pressure, and rarely, pigs are a common sight in destitute communities. In death. 28,36,37,39 Side effects, although usually mild, include contrast to other flocks, pigs can be fed human faeces, nausea, headache, seizures, and occasionally, cerebral are resistant to many adverse environmental conditions, edema. 39 Deaths associated with antiparasitic treatment reach a large body size early in life, and are easily are rare (1% to 4%) and occur primarily in patients with domesticated. Additionally, the fact that these pigs are hydrocephalus, increased intracranial pressure, and heavy fed human waste and the problem of wandering pigs, cyst burden (i.e., more than 20 cysts). 28 In the ûrst which constitute the link in the life cycle of taenia-sis and randomized comparison of al-bendazole, praziquantel, and cysticercosis in humans is not as easy to break by simple steroids for the treatment of active cysts, Carpio found measures such as confiscating infected meat, no signiûcant difference in seizure-free rates among the recommending the use of appropriate, but costly, pork three treatment groups. Recently, however, the food, and sheltering of animals. 48 The most cost effective Cysticercosis Working Group in Peru compared the perspective for eradication of cysticercosis, as with many efûcacy and safety of albendazole (400 mg twice a day) other diseases, is by edu-cation and public awareness of with placebo for the treatment of active cysts as-sociated the real source of infection. The ingestion of undercooked with seizures. 43 However, patients randomized to pork infected with cysticerci is the exclusive path to the albendazole experienced a signiûcant (67%) reduction in development of intestinal taenia, which closes the life generalized tonic–clonic seizures compared with the cycle of the parasite. This misinformation poses obstacles for cost effective preventive measures. 48 Public educationand sanitary measures are the essential factors for the Prior to the advent of antiparasitic drugs, surgery wasthe primary therapy for neurocysticercosis, mainly open Conclusions
surgery for excision of large cysts or cysts in the Neurocysticercosis is a leading cause of epilepsy in ventricles. The role of surgical therapy in the management the devel-oping world and is increasingly prevalent in the of neurocysticer-cosis has signiûcantly decreased over developed countries also. Treatment with albendazole has time and is now mainly restricted to placement of signiûcantly improved the outcome in patients with ventricular shunts for hydrocephalus secondary to neurocysticercosis. However better understand-ing of the neurocysticercosis. The main problem in these cases is mechanisms of neurocysticercosis; the life cy-cle of T.
the high prevalence of shunt dysfunction; indeed, it is solium and life style and sanitation habits of the common for patients with hydrocephalus secondary to population is needed to develop appropriate intervention neuro-cysticercosis to have two or three shunt revisions.
Nepal Journal of Neuroscience, Volume 4, Number 1, 2007 Neurocysticercosis
References
18. Carpio A, Hauser A: Prognosis for seizure recurrence in patients with newly diagnosed Relationship between epilepsy and tropical neurocysticercosis. Neurology 59:1730–1734, 2002
disease. Epilepsia 35: 89–93, 1994
19. Dur´on R, Medina MT, Osorio J, et al: Prognosis Rao KRS, Lessing D: Neurocysticercosis in West of the epilepsy due to neurocysticercosis: A ûve- London. Arch Dis Child 88:467–471, 2003
year follow-up from the Salam´a epilepsy study in White AC Jr: Neurocysticercosis: a major cause Honduras. Epilepsia 44(suppl.8):38, 2003
of neurological disease worldwide. Clin Infect Dis
20. Sanchez AL, Ljunstrom I, Medina MT: Diagnosis 19:101-115, 1997
Bern C, Garcia HH, Evans C, Gonzalez AE, et al: countries: A clinical study in Honduras. Parasitol
Int 48:81–89, 1999
neurocysticercosis in a develop-ing country. Clin
21. Dixon, HB, Lipscomb, FM: Cysticercosis: an
Infect Dis 29:1203–1209, 1999
analysis and follow-up of 450 cases (vol 31). 1961,
Sarti E, Schantz PM, Plancarte A, Wilson M, et al.
Medical Research Council, London, UK.
Prevalence and risk factors for Taenia solium 22. Del Brutto OH, Sotelo J: Neurocysticercosis: an taeniasis and cysticerco-sis in humans and pigs update. Rev Infect Dis 10:1075–1087, 1988
in a village in Morelos, Mexico. Am J Trop Med
23. White AC Jr: Neurocysticercosis: Updates on Hyg 46:677–685, 1992
epidemiology, pathogenesis, diagnosis, and Medina MT, Rosas E, Rubio-Donnadieu F, and management. Annu Rev Med 51: 187-206, 2000.
Sotelo J: Neurocysticercosis as the main cause of 24. Bucardo F, Meza-Lucas A, Espinoza F, Garcia- late-onset epilepsy in Mexico. Arch Intern Med
Jeronimo RC, Garcia-Rodea R, Correa D. The 150:325–327, 1990
seroprevalence of Taenia solium cysticercosis Brailsford, JF: Cysticercus cellulosae-Its among epileptic patients in Leon, Nicaragua, as radiographic detection in the musculature and the evaluated by ELISA and western blotting. Ann
central nervous system. Br J Radiol XIV:79–93,
Trop Med Parasitol 99: 41-45, 2005
25. Garcia HH, Del Brutto OH: Taenia solium cysticercosis. Infect Dis Clin North Am 14: 97-
development of Taenia solium: III. On the development of cysticercus cellulosae within the 26. Rabiela, M, Rivas, A: Morphological types of deûn-itive intermediate host. J Med Assoc
Taenia solium cysticerci. Parasitol. Today 5:357–
Formosa 32:166–169, 1933
DeGiorgio CM, Medina MT, Dur´on R, Zee , 27. Bickerstaff ER, Cloake CP, Hughes B, and Smith Es-cueta SP. Neurocysticercosis. Epilepsy
WT: The racemose form of cerebral cysticercosis.
Currents 4:107–111, 2004
Brain 75:1–18, 1952
28. DeGiorgio CM, Houston I, Oviedo S, and Sorvillo Neurocysticercosis: a clinical handbook. 1997,
F: Death associated with cysticercosis: Report of Swets and Zeitliger, Lisse, The Netherlands.
three cases and review of the literature.
11. Garcia HH, Del Brutto OH: Taenia solium Neurosurg Focus 12:1–4, 2002
cysticercosis. Infect Dis Clin North Am 14:97–
29. Escobar A: The pathology of neurocysticercosis, p. 27–54. In E. Palacios, J. Rodriguez-Carbajal,
12. Garcia HH, Martinez SM: Taenia solium taeniasis/
and J. M. Taveras (ed 4), 1983; Cysticercosis of
cysticercosis (ed 2). Universo, 1999,Lima, Peru.
13. Flisser A: Taeniasis and cysticercosis due to Taenia 30. Flisser A, Gonzalez D, Shkurovich M, et al.
solium. Prog Clin Parasitol 4:77–116, 1994
Praziquantel treatment of porcine brain and muscle 14. White AC Jr., Robinson P, Kuhn R: Taenia solium Taenia solium cysticercosis. 1. Radiological, cysticercosis: host-parasite interactions and the physiological and histopathological studies.
immune response. Chem Immunol 66:209–230,
Parasitol Res 76:263–269, 1090
31. Trelles JO, Trelles L. 1978. Cysticercosis of the 15. Garcia-Noval J, Allan JC, Fletes C, et al: nervous system, p. 291–320. In JN Wynken and G Epidemiology of Taenia solium taeniasis and W Bruyn (eds): Handbook of Clinical Neurology,
cysticercosis in two rural Guatemalan communities.
Am J Trop Med Hyg 55:282-289, 1996
16. Carpio A, Escobar A, Hauser WA: Cysticercosis 32. Del Brutto OH, Wadia NH, Dumas M, Cruz M, and epilepsy: a critical review. Epilepsia 39:1025-
Tsang VC, Schantz PM. Proposal of diagnostic 17. Del Brutto OH, Santibanez R, Noboa CA, et al: neurocysticercosis. J Neurol Sci 142:1–6, 1996
Epilepsy due to neurocysticercosis: Analysis of 33. Del Brutto OH, Rajshekhar V, White AC Jr, et al: 203 patients. Neurology 42:389–392, 1992
Proposed diagnostic criteria for
neurocysticercosis. Neurology 57:177–183, 2001
Nepal Journal of Neuroscience, Volume 4, Number 1, 2007 Agrawal & Khanal
34. Garcia MR, Astiazarán AG, Franco FR: 43. Garcia HH, Pretell J, Gilman R, Martinez SM, Neurocysticercosis in children: clinical experience Moulton LH, del Brutto O, Herrera G, Evans CA, in 122 patients. Child’s Nerv Syst 13:608-612, 1997
Gonzalez AE and the Cysticer-cosis Working 35. Evans C, Garcý´a H, Gilman R, et al: Controversies Group in Peru: A trial of antiparasitic treatment in the management of cysticercosis. Emerg Infect
to reduce the rate of seizures due to cerebral Dis 3:403–405, 1997
Cysticercosis. N Engl J Med 350:259–258, 2004
36. Garcia HH, Gonzales AE, Evans CAW, and Gilman 44. Bang OY, Heo JH, Choi SA, et al: Large cerebral RH: Taenia solium cysticercosis. Lancet 362:547–
infarction during praziquantel therapy in neurocysticercosis. Stroke 28:211–213, 1997
37. Carpio A: Neurocysticercosis: An update. Lancet
45. C Márquez-Caraveo, F Góngora-Rivera, J Santos Infect Dis 2:751–762, 2002
38. Medina MT, Genton P, Montoya MC, et al. Effect corticosteroids and a single cycle of high dose of the anticys-ticercal treatment on the prognosis albendazole for subarachnoidal cysticercosis.
of epilepsy in neurocysticer-cosis: A pilot trial.
J Neurol. Neurosurg. Psychiatry 75:938-939,
Epilepsia 34:1024–1027, 1993
39. Salinas R, Counsell C, Prasad K, et al: Treating 46. Proan˜o J, Madrazo I, Avelar F, et al: Medical neurocysticercosis medically: A systematic review treatment for neurocysticercosis characterized of randomized, controlled trials. Trop Med Int
by giant subarachnoid cysts. N Engl J Med
Health 4:713–718, 1999
345:879–885, 2001
40.Sotelo J, Escobedo F, Rodr´ýguez, et al. Therapy 47. Prasad KN, Chawla S, Jain D, Pandey CM, Pal L, Pradhan S, et al: Human and porcine Taenia praziquantel. N Engl J Med 310:1001–1007, 1984
solium infection in rural north India. TransR Soc
41. Sotelo J, Del Brutto OH, Penagos P, et al.
Trop Med Hyg 96:515-516, 2002
48. Sotelo J: Eradication of cysticercosisis an anticysticercal drugs for parenchymal brain attainable goal. BMJ 326:511–512, 2003
cysticercosis. J Neurol 237:69–72, 1990
49. Nieto D: Historical notes on cysticercosis. In: 42. Vasquez N, Sotelo J: The course of seizures after Flisser A, Willms K, Laclette JP, et al(eds).
treatment for cerebral cysticercosis. N Engl J Med
Cysticercosis: present state of knowledge and
327:696–701, 1992
perspectives. New York: Academic Press, 1982:1-7
Nepal Journal of Neuroscience, Volume 4, Number 1, 2007

Source: http://www.neuroscience.org.np/x2.pdf