Neurocysticercosis in children

Symposium on Neurological Disorder–Advances in Management-II Neurocysticercosis in Children Pratibha Singhi and Sunit Singhi Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India ABSTRACT Neurocysticercosis (NCC) is a common cause of seizures and neurologic disease. Although there may be variable presentations depending on the stage and location of cysts in the nervous system, most children (> 80%) present with seizures particularly partial seizures. About a third of cases have headache and vomiting. Diagnosis is made by either CT or MRI. Single enhancing lesions are the commonest visualization of a scolex confirms the diagnosis. Some cases have multiple cysts with a characterstic starry-sky appearance. Management involves use of anticonvulsants for seizures and steroids for cerebral edema. The use of cysticidal therapy continues to be debated. Controlled studies have shown that cysticidal therapy helps in increased and faster resolution of CT lesions. Improvement in long - term seizure control has not yet been proven. Children with single lesions have a good outcome and seizure recurrence rate is low. Children with multiple lesions have recurrent seizures. Extraparenchymal NCC has a guarded prognosis but it is rare in children. In endemic areas NCC must be considered in the differential diagnosis of seizures and various other neurological disorders. [Indian J Pediatr 2009; 76 (5) : 537-545] Email: pratibhasinghi@yahoo.com Key words : Neurocysticercosis (NCC); Seizures; Cysts; Diagnosis; Management Neurocysticercosis (NCC) is a major cause of neurological disease world-wide.1,2 It is an important cause of epilepsy in the tropics3 and was found to be the commonest cause of focal seizures in North Indian children.4 Although predominantly seen in developing countries, it is also seen in many developed countries mainly because of increasing number of immigrants from endemic areas. Inspite of its recognition for several years, many aspects related to diagnosis and management remain controversial. contagious eggs in the stools. Pigs are the intermediate hosts and get infected by eating food contaminated with parasitic eggs passed in human faeces. The eggs hatch into larvae in the pigs’ intestine and cross the mucosa, to reach tissues, where they mature into cysticerci over a period of 3 weeks to 2 months. When humans consume undercooked pork containing the cysts, the life cycle of the parasite is completed. Neurocysticercosis is caused by infestation of the CNS with encysted larvae of Taenia solium. It must be distinguished from taeniasis which represents intestinal infection with T Solium that is acquired from pigs by ingestion of undercooked pork infected with cysticerci. The larvae from these cysticerci evaginate and develop into adult worms which live in the intestine and shed thousands of extremely NCC on the other hand is acquired through the faeco-oral route. Infection occurs when humans eat raw vegetables contaminated with T Solium eggs or food prepared by carriers of tapeworms. Very rarely infection may occur due to autoingestion of ova in patients who have intestinal tape worms. As in pigs, in the human intestine the eggs hatch to release larvae that penetrate the intestinal mucosa, and migrate throughout the body to produce human cysticercosis. Although the cysts may be found in any human tissue, most mature cysts are found in the CNS, skeletal muscle, subcutaneous tissue, and the eyes. Generally the cysts tend to locate in areas with high blood flow especially the grey white matter junction. Correspondence and Reprint requests : Dr Pratibha Singhi, Professor of Pediatrics, Chief, Pediatric Neurology and Neuro Development, Department of Pediatrics, PGIMER, Chandigarh160 012, India. Fax: 91-172-2744401 & 2745078 [Received March 17, 2009; Accepted March 17, 2009] (i) Pathogenesis: Cycsticerci often live asymptomatically within host tissues for years as they have developed various mechanisms for evading host response. 5 Metacestodes secrete a serine protease inhibitor- taeniaestatin which inhibits complement activation and cytokine production and interferes with ETIOLOGY Life cycle of the parasite Indian Journal of Pediatrics, Volume 76—May, 2009 537 Pratibha Singhi and Sunit Singhi leukocyte chemotaxis. Parasite paramyosin also binds to C1q and inhibits the classic pathway of complement activation. The cellular immune response is also suppressed.5 The cyst has 4 stages 1. Vesicular Stage (Metacestode)- The parasite lives in tissues as a fluid- filled cyst with a thin semitransparent wall. The scolex lies invaginated on one side of the cyst and appears as an opaque 4-5 mm nodule. These viable cysts are generally asymptomatic. Once the cysts start degenerating, an inflammatory response is elicited and the cyst goes through the following stages2. Colloidal stage: The larva undergoes hyaline degeneration and gelatinous material appears in cyst fluid. 3. Granular nodular stage: The cyst contracts and the walls are replaced by focal lymphoid nodules and necrosis. 4. Nodular calcified stage: The granulation tissue is replaced by collagenous structures and calcification (6). CLINICAL MANIFESTATIONS These are pleomorphic and are determined mainly by the location, number and viability of the cysts as well as by the host response. NCC is generally classified into (a) parenchymal and (b) extra parenchymal which includes ventricular, cisternal, ophthalmic or spinal. Most children present with single degenerating parenchymal cysts, some with multiple cysts. It is not clearly understood as to why some cases have single and others have multiple cysts. Immunological differences may possibly account for this; defective functions of neutrophils and T lymphocytes have been reported in patients with multiple lesions only and not in those with single lesions.7 Parenchymal NCC Most cases of childhood NCC are seen after five years of age although some cases are seen in preschoolers and even in infants. The common clinical manifestations include: (i) Seizures. Sudden onset of seizures in otherwise healthy children is the commonest presentation. Seizures occur in 70-90% of cases; in a series of 500 children from India, seizures were reported in 94.8% cases.8 Most children present with partial seizures (8487%)8,9,10 particularly complex partial seizures; about a quarter have simple partial seizures.8 Most seizures are of short duration, generally lasting for less than 5 minutes. Status epilepticus has been reported in 1.7% to 538 32% cases. 8,9,10 Seizures are generally single; in a hospital based study, NCC was discovered on imaging in 59.2% of cases with single seizures.11 Depending on the stage of the disease, the seizures may be considered provoked or unprovoked, and these may co-exist. Although it is presumed that degeneration of the cysts and the associated inflammatory response evoke seizures, this has been questioned in a recent study wherein 29% asymptomatic family members of symptomatic cases were diagnosed to have NCC. A large number of individuals harboring different stages of cysticerci in their brain were asymptomatic.12 NCC has been found to be associated with mesial temporal lobe epilepsy due to hippocampal sclerosis –this may provide new insights into epileptogenesis.13 (ii) Raised intracranial pressure: headache and vomiting occur in almost a third of cases. 10 Papilloedema has been reported in 2.3 9 to 6.6% of children.8 Signs of raised ICP and papilleodema are less common in children as compared to adults. (iii) Focal Neurodeficits: determined by the location of the cysts. Transient hemiparesis, monoparesis, and oculomotor abnormalities are common. Focal deficits were seen in 4% of children, 8 as compared to 16% of adults. 14 (iv) Cysticercal Encephalitis: rarely massive cyst burden with diffuse cerebral edema may present with severe acute raised intracranial pressure and an encephalitic picture in some children and adolescents. These cases are difficult to treat and have high mortality and neuromorbidity. Extraparenchymal NCC: This is rare in children as compared to adults. (i) Ventricular and Subarachnoid NCC: generally occur together and present as basilar arachnoiditis, obstructive hydrocephalous or chronic meningitis. Some subarachnoid cysts may enlarge without scolices, become racemose and cause mass effects . Seizures may occur in cases with associated parenchymal NCC. (ii) Spinal cysticercosis: is rare (1-5%) in children. Cysts are generally located in the leptomeningeal space but may occasionally be found within the cord. Radicular pain, paresthesias, and spinal cord compression may occur. Intramedullary cysts may present as transverse myelitis with paraplegia and sphincteric disturbances. (iii) Ophthalmic cysticercosis: cysts may lodge anywhere in the eyes including the subretinal space, vitreous humor, subconjuctiva or anterior chamber. Symptoms occur accordingly and include visual deficits, sudden blindness, limitation of eye movements etc. Indian Journal of Pediatrics, Volume 76—May, 2009 Neurocysticercosis in Children Unusual presentations: These are variable and include communicating hydrocephalous, vasculitis, stroke,15 learning disability and behavioural changes, dorsal midbrain syndrome, ptosis, papillitis, cerebral hemorrhage, dystonia,. neurocognitive deficits and psychiatric morbidity particularly depression syndromes in adults.16 DIAGNOSIS NCC should be considered in the differential diagnosis of patients with seizures, headache, vomiting and other neurological symptoms and signs. Since pathologic confirmation of the parasite is hardly ever feasible, diagnosis rests mainly on neuroimaging. CT Scan Fig. 1B. Single Small Enhancing CT Lesion- disc. (a) Parenchymal NCC The appearance of cysts on CT varies with the stage. Vesicular cysts generally appear as small round lesions with CSF density cystic fluid; the wall is isodense to the brain parenchyma. They are non-enhancing or mildly enhancing and are not surrounded by edema. Degenerating (colloidal vesicular) cysts appear as small low-density lesions with ring or disc enhancement (Fig 1A , B). The scolex appears as a bright high density eccentric nodule in these cysts and is pathognomonic of NCC. Perilesional edema of varying grades is seen in over half the cases. In most cases the lesions are single and <20mm in size- termed as single small enhancing computed tomographic lesion (SSECTL).17 Fig 1(A and B). Some children may have multiple lesions; disseminated NCC with numerous cysts may give the so called “starry –sky” appearance which is typical of NCC (Fig. 2). Calcified cysts are few mm in size, single or multiple and generally without any surrounding; oedema. However in children with active seizures, Fig. 2. CT scan showing Multiple Neurocysticercosis. oedema may at times be seen around calcified lesions.18 (b) Extraparenchymal NCC In subarachnoid NCC, the CT may show hydrocephalous, enhancement of tentorium and basal cisterns due to arachnoiditis and occasionally infarcts. Very raely, racemose cysts may be seen as cystic hypodense lesions in the sylvian fissure or cerebellopontine angle. Rarely intraventricular cysts may cause obstruction and hydrocephalous . MRI Fig. 1A. Single Small Enhancing CT Lesion- ring with scolex and perilesional edema. Indian Journal of Pediatrics, Volume 76—May, 2009 Identification of scolex and visualization of extraparenchymal cysts is better with MRI . Live cysts are seen as round lesions either isointense or slightly hyperintense to the CSF. The scolex is seen as a nodule 539 Pratibha Singhi and Sunit Singhi that is isointense or hyperintense relative to white matter. On T2 weighted images, the perilesional oedema appears bright and because of the high intensity cystic fluid, the scolex may not be seen. The scolex is better seen on proton density –weighted images. Gadolinium enhanced MRI shows ring enhancement of lesion. Calcified lesions appear hypointense on all MR imaging sequences and may at times be missed. The issue about which MRI sequence is best suited for NCC has been discussed.19 brain lesions (100%) than in in those with single-lesion (87%).26 The detection of antibodies to antigens of 26 Kda and 8 RDA by immunoblot using a crude antigenic preparation of T. Solium cysticercci has been shown to approach 100% specificity but is less sensitive than the glycoprotein based EITB 27 and has been less extensively assessed. Lower molecular mass (20-24 kDa) Taenia solium cysticercus antigen fraction by ELISA and dot blot for the serodiagnosis of neurocysticercosis in children has also been evaluated. 28 For usual cases of suspected NCC, getting a CT scan is enough ; however MRI is more sensitive for detecting scolex and extraparenchymal NCC.20 In cases where the scolex is not well seen, it may be difficult to make the diagnosis of NCC with certainity; other sophisticated imaging techniques are therefore being researched. Proton Magnetic Resonance Spectroscopy (MRS) has been tried for evaluation of inflammatory granulomas. 21 It has been suggested that presence of lipid indicates a tuberculoma whereas low levels of metabolites together with a poor signal/noise ratio could indicate NCC. 3D constructive interference in Steady State (3DCISS) - In a study, it was found to be more sensitive and specific than routine SE sequences in the diagnosis of intraventricular cysticercal cysts.-scolex was seen in all 11 patients.22 DWI MRI Higher apparent diffusion co-efficient (ADC) is seen in core of cysticercus cysts compared to tuberculomas and tubercular abscess.23 Most of these imaging techniques are investigational and are not routinely used. Serological Tests None of the several immunologic tests that have been developed, is very sensitive or specific for diagnosis of NCC particularly for single lesions. Low positivity from 17 to 25% has been reported in children with NCC.8,9 The widely used Enzyme Linked Immunosorbent Assay (ELISA) showed 50% sensitivity and 65% specificity in the CSF. 24 The Enzymelinked immunoelectro transfer blot (EITB) assay using purified glycoprotein antigens from T. Solium cysticerci has been reported to be highly specific and nearly 100% sensitive for patients with either multiple active parenchymal cysts or extraparenchymal NCC. 25 However, sensitivity is less for patients with either single cysts or calcifications alone. In a comparative study of ELISA and dot-blot assay, in children aged 512 yr, both assays were more sensitive in the detection of the specific antibody response, in cases with multiple 540 Other Tests (i) X-Rays: Calcified cysts may be detected in skeletal muscles –however X-rays are not routinely done in children with NCC. (ii) Stool examination for tapeworms is not helpful in diagnosis of NCC. (iii) Biopsy of subcutaneous nodules in a patient with suspected NCC, can corroborate the diagnosis in doubtful cases. (iv) Blood: Peripheral eosinophilia is variably reported in about one third of cases. (v) CSF : Analysis is is not routinely indicated in cases of parenchymal NCC; if done it is normal in most cases. In patients with NCC meningitis, CSF may show mild elevation of protein with some pleocytosis and hypoglycorrhachia. The cellular response may be lymphocytic, polymorphonuclear or monocytic. Other laboratory tests are usually normal in NCC To ensure uniformity in diagnosis, criteria for human cysticercosis and neurocysticercosis incorporating clinical, radiological, immunologic and epidemiologic data of patients were proposed in 199629 and revised in 200030 Four degrees of criteria- absolute, major, minor and epidemiologic were selected to give a definitive or a probable diagnosis. However, in view of the pleomorphism of the disease, NCC should be kept in the differential diagnosis of a wide variety of neurologic disorders particularly seizures, and appropriate neuroimaging studies should be undertaken to confirm the diagnosis. DIFFERENTIAL DIAGNOSES Parenchymal NCC. When the scolex is not well seen, a number of conditions need to be considered in the differential diagnosis of SSECTL. These include (i) Tuberculoma this is the commonest differential diagnosis in developing countries. Certain criteria such as the presence of raised ICP, progressive focal neurodeficit, size of CT lesion> 20 mm, Indian Journal of Pediatrics, Volume 76—May, 2009 Neurocysticercosis in Children lobulated irregular shape, and marked edema causing midline shift favour the diagnosis of tuberculoma,31 but are not absolute.Tuberculomas are most often seen in the posterior fossa or base of the brain whereas NCC lesions are seen near the gray white junction of the cortex. Mantoux test, Xray chest and other tests for exclusion of tuberculosis should be done in all cases of enhancing lesions where the scolex is not seen. (ii) Other differential diagnoses include microabscess, low grade astrocytoma, cystic cerebral metastasis, toxoplasmosis and fungal lesion.17 Extraparenchymal NCC. Hydrocephalous with racemose NCC in the subarachnoid space may simulate a low density tumor. Meningitis due to NCC needs to be differentiated from other causes of chronic meningitis. TREATMENT Therapeutic measures for NCC may be considered as: (i) Symptomatic/supportive (ii) Definitive- medical/surgical treatment for cysts Symptomatic (a) Anticonvulsants: As most cases present with seizures, antiepileptic drugs (AED) are required. The seizures are usually controlled with a single anticonvulsant. Recurrence of seizures after discontinuation of AEDs has been variably reported. In children with SSECTL, seizure recurrence is low and varies from 10 to 20% of cases.9,32 a higher recurrence rate of 54.4% was reported in one study of 28 children with NCC.33 The rate of recurrence is generally higher (40- 50%) in adults.34 The duration of AED therapy has been debated. The conventional practice has been to use AED for about two years seizure free interval. However, shorter durations of AED may be sufficient.35 A randomised controlled prospective study found no difference in seizure recurrence when AEDs were given for a one year vs two years seizure free interval. 36 Seizure recurrence correlated significantly with an abnormal CT (persistence or calcification of lesion) and an abnormal EEG at the time of withdrawal. Children having both CT and EEG abnormalities were at a significantly higher risk of seizure recurrence.36 Thus anticonvulsant therapy may be withdrawn after oneyear seizure free interval in those children where the lesion has disappeared and the EEG is normal prior to withdrawal. Children with persistent or calcified lesions may require longer therapy. Shorter durations of AEDs for three months have Indian Journal of Pediatrics, Volume 76—May, 2009 also been tried. However, in a study (personal unpublished data) this was associated with a higher seizure recurrence as compared to one year therapy. Most cases have partial seizures hence carbamazepine is the preferred drug: Other AEDs could also be used, provided the efficacy and side effects are carefully considered. (b) Corticosteroids: A short course of corticosteroids is generally used concomitantly with anticysticercal therapy to prevent or ameliorate any adverse reactions that may occur due to the host inflammatory response during the active inflammatory phase. 37 Acute symptomatic patients who have cerebral edema on neuroimaging, may be given oral prednisolone 1-2 mg/ kg or I.V dexamethasone if there are features of raised ICP. Rarely steroids may be required for several weeks particularly in children with disseminated lesions and extensive cerebral oedema. Definitive Therapy The debate whether medical treatment for NCC is effective or ineffective has continued for long even though praziquantel and albendazole have been found effective against T. Solium cysticerci in several studies. The two main outcome measures of cysticidal therapy are (i) cyst destruction and (ii) seizure control. Cyst Destruction Both praziquantel and albendazole were found to be effective in destroying viable cysts. 38,39,40,41 The main controversy revolves around the use of these agents in cases with enhancing lesions as these are considered to represent degenerating cysts. In the first double-blind placebo controlled trial in 63 children, in whom albendazole (15mg/kg/dayx 4 weeks) was given within 3 months of onset of seizures there was an increased and faster resolution of SSECTL. 42 Disappearance of lesions was seen in 41% of albendazole vs 16.2% of placebo treated patients after 1 month (p < 0.05) and 64.5% of albendazole vs 37.5% of placebo treated patients after 3 months of follow up (p <0.05). Subsequently other trials have also shown increased disappearance of lesions with albendazole. 43,44,45 However, in a placebo-controlled study that included adults after variable times (1 day to 6 years) of onset of seizures, no beneficial effect of albendazole therapy was observed.46 A meta- analysis 47 of all studies of anticysticercal treatment of NCC from 1966- June 1999, could find only 4 trials in which albendazole or praziquantel was compared with either placebo or no treatment, using randomised or quasirandomised method. It revealed lower risk of cyst persistence in CT at 6 months among those who received anticysticercal therapy. The same authors updated the meta-analysis in 2007 and 541 Pratibha Singhi and Sunit Singhi concluded that there is insufficient evidence to assess whether cysticidal therapy in neurocysticerosis is associated with beneficial effects. 48 However, another meta-analysis of studies between 1979 and 2005 included eleven studies -six trials randomly assigned 464 patients with cystic lesions (vesicular cysticerci), and 5 trials randomly assigned 478 patients with enhancing lesions (colloidal cysticerci). In trials of vesicular lesions, cysticidal therapy was associated with complete resolution of cystic lesions (44% vs 19%; P = 0.025). Trials on enhancing lesions showed a trend toward lesion resolution favoring the use of cysticidal drugs (72% vs 63%; P = 0.38) that became statistically significant when an outlier trial was excluded from the analysis (69% vs 55%; P = 0.006). 49 On the basis of evidence, cysticidal therapy is effective in increasing the destruction of viable cysts as well as the resolution of enhancing lesions. CLINICAL OUTCOME Improved seizure control after cysticidal therapy has been reported in some studies. A strong correlation between the use of anticysticercal drugs and the rate of seizure control was found in adults with epilepsy due to NCC.14,50,51 It was also found that focal neurodeficits improved after treatment with anticysticercal drugs. An improved outcome was reported in 80% of patients in whom treatment was given soon after recognition of SSECTL.52 In a double-blind, placebo-controlled trial in which 120 patients who had living cysticerci in the brain, cysticidal therapy was effective, at least in reducing the number of seizures with generalization.53 However, other studies have not found any significant improvement in seizure control both in patients with live cysts and multiple or single enhancing lesions.32,45,54 In a meta analysis of randomised studies referred above, 47 Salinas et al could find only two controlled studies which had studied seizure control as an outcome. The authors did not report decrease in seizure recurrence; however, the numbers studied were small. On the other hand, in the meta-analysis of randomised studies by del Brutto et al,49 risk for seizure recurrence was lower after cysticidal treatment in patients with enhancing lesions (14% vs 37%; P < 0.001). The single trial evaluating the frequency of seizures in patients with cystic lesions showed 67% reduction in the rate of generalized seizures with treatment (P=0.006). On balance, there is insufficient evidence to determine whether cysticidal therapy improves long term seizure control and larger studies are required to answer this question. Choice of Cysticidal Drug Although both praziquantel and albendazole have been found effective in NCC, Albendazole is better than 542 praziquantel,40,41 is less expensive and better tolerated. It also has a greater penetration into the subarachnoid space and is therefore better for treatment of subarachnoid NCC. Also, bioavailability of albendazole increases with co-administration of steroids and is not affected by phenytoin and carbamezepine, 55 whereas that of praziquantel decreases with co-administration of steroids,56 and with phenytoin and carbamezepine which are generally used as first line anticonvulsants in patients with seizures due to NCC.57 Albendazole is currently the drug of choice for treatment of NCC . Albendazole has been used in a dose of 15 mg/kg/ day in 2-3 divided doses for 28 days.35 Shorter durations of 14 days to 8 days have also been used.35 In a placebocontrolled trial of one week vs four weeks albendazole therapy in children with one to three enhancing lesions both the regimens were found to be equally effective.58 Resolution of lesions on 3 months CT was seen in 68.3% and 68.8% in the one week and four weeks treatment groups respectively. Seizure control at 1 year was similar in both the groups.58 Albendazole has also been used successfully for the treatment of spinal NCC, 59 and meningeal NCC. In cases with subarachnoid giant cysts, 60,61 steroids are recommended before, during and after albendazole therapy to prevent cerebral infarction which may occur secondary to occlusive endarteritis induced by the host inflammatory response. Praziquantel has been generally used in a dose of 50mg/kg/day for a period of 15 days. A single day praziquantel therapy (25 mg/ kg/dose every 2 hours x 3 doses) has been reported to be as effective as 7 days treatment with albendazole.62 optimisation of single day therapy with a high carbohydrate diet and cimetidine reportedly induced 83% elimination of cysticerci.63 A combination therapy of albensazole and praziqunatel was found to have no significant difference in the outcome of single lesion NCC as compared to albendazole alone (although it was associated with a trend to higher resolution). 64 Cysticidal therapy should not be used in cases with (i) markedly raised ICP particularly in disseminated NCC as sudden elevations of ICP may occur secondary to the host inflammatory response. and in (ii) ophthalmic NCC -as the host response may cause damage to the eye. Such cases should be treated with steroids alone. Cysticidal therapy is not indicated for calcified lesion (s) as the parasite is already dead and buried. In view of the controversies involved, consensus guidelines for the treatment of NCC were published.35 and rediscussed.65 As NCC is a pleomorphic disease, treatment approaches differ among the forms or types of NCC and need to be individualized. Surgery Some cases with hydrocephalous may need shunt Indian Journal of Pediatrics, Volume 76—May, 2009 Neurocysticercosis in Children placement; steroids and albendazole are used concomitantly to reduce shunt failure. Successful endoscopic removal of cysts from the lateral, third and fourth ventricles may obviate the need for shunt66,67 and may be safer, faster, and curative with better long-term clinical outcomes. Rarely, surgical removal may be required in some cases of ophthalmic NCC; almost all of these studies are in adults as extraparenchymal NCC is rare in children Follow up This needs to be individualized. For single enhancing lesions, a repeat CT after 3-6 months is generally indicated to determine whether the lesions have resolved.68 Outcome The outcome depends upon the type of NCC, cyst location and numbers. In general parenchymal NCC has a better prognosis than extraparenchymal NCC and single lesions have a better outcome as compared to multiple lesions. In most children with seizures and single parenchymal cysts seizures are well controlled and lesions disappear within 6 months in over 60% cases. Risk of seizure recurrence is low. Cases with multiple lesions particularly disseminated NCC and calcifications have frequent seizure recurrences. A genetic susceptibility to NCC has been suggested by a reported positive association of HLA- DRBII 13 with SSECTL(s).69 Prevention NCC is a disease perpetuated by poor hygiene and sanitation. Lack of proper animal husbandry and meat inspection procedures in developing countries, wherein pigs are left to scavenge for food from open sewage systems, are responsible for ongoing transmission. Preventive efforts have to be directed against these. Mass treatment of population with praziquantel to eradicate human taeniasis resulted in marked reduction in intestinal tapeworm carriage and rate of porcine cysticercosis in Equador 70 and in Mexico.71 However, these programs were shown to be ineffective when reevaluated some years after their application.72 Public awareness and insistence on hygiene and sanitation are of utmost importance. CONCLUSION Neurocysticercosis is the commonest cause of acquired seizures in children. As neurocysticercosis may have variable neurological manifestations, it needs to be considered in the differential diagnosis of a number of neurological diseases. Treatment with cysticidal drugs is associated with increased and faster resolution of lesions and is usually well tolerated; however it needs Indian Journal of Pediatrics, Volume 76—May, 2009 to be individualized. Children with single or few lesions have a good outcome whereas those with multiple lesions often have recurrent seizures. Public sanitation and hygiene are of utmost importance in prevention. REFERENCES 1. White AC. Neurocysticercosis: A major cause of neurological disease worldwide. Clin Infect Dis 1997; 24: 101-115. 2. Roman G, Sotelo J, Del Brutto O et al. A proposal to declare neurocysticercosis an international reportable disease. Bull World Health Organ 2000; 78: 399-406. 3. Commission on Tropical Diseases of the International League Against Epilepsy. Relationship between Epilepsy and tropical diseases. Epilepsia 1994; 35: 89-93. 4. Singhi S, Singhi P. Clinical profile and etiology of partial seizures in North Indian Infants and children. J Epilepsy 1997; 10: 32-36. 5. Leid RW, Suquet CM, Tanigoshi L. Parasite defense mechanisms for evasion of host attack: a review. Vet Parasitol 1987; 25: 147-162. 6. Escobar A. The pathology of neurocysticercosis. In Palacios E, Rodriguez- Carbajal KJ, Taveras J, eds. Cysticercosis of the central nervous system. Illinois: Springfield, Charles C Thomas, 1983; 27-54. 7. Thussu A, Sehgal S, Sharma M, Lal V, Sawhney IMS, Prabhakar S. Comparison of cellular responses in single and multiple lesions neurocysticercosis. Ann Trop Med Parasitol 1997; 91: 627-632. 8. Singhi P, Ray M, Singhi S, Khandelwal N. Clinical spectrum of 500 children with neurocysticercosis and response to albendazole therapy. J Child Neurol 2000; 15: 207-213. 9. Talukdar B, Saxena A, Popli VK, Choudhury V. Neurocysticercosis in children: clinical characteristics and outcome. Annals Trop Pediatr 2002; 22: 333-339. 10. Morales NM, Agapejev S, Morales RR, Padula NA, Lima MM. Clinical aspects of neurocysticercosis in children. Pediatr Neurol 2000; 22: 287-291. 11. Singh G, Singh P. Singh I, Rani A, Kaushal S, Avasthi G. Epidemiologic classification of seizures associated with neurocysticercosis: observations from a sample of seizures disorders in neurologic care in India. Acta Neurol Scand 2006; 113: 233-240. 12. Prasad A, Gupta RK, Pradhan S, Tripathi M, Pandey CM, Prasad KN. What triggers seizures in neurocysticercosis? A MRI- based study in pig farming community from a district of North India. Parasitol Int 2008; 57: 166-171. 13. Wichert-Ana L, Velasco TR, Terra-Bustamante VC et al. Surgical treatment for mesial temporal lobe epilepsy in the presence of massive calcified neurocysticercosis. Arch Neurol 2004; 61 : 1117–1119. 14. Del Brutto OH, Santibanez R, Noboa CA et al. Epilepsy due to neurocysticercosis: Analysis of 203 patients. Neurology 1992; 42 : 389-392. 15. Del Brutto OH. Cysticercosis and cerebrovascular disease: a review. J Neurol Neurosurg Psychiatry 1992; 55 : 252-254. 16. Forlenza OV, Filho AH, Nobrega JP et al. Psychiatry manifestations of neurocysticercosis; a study of 38 patients from a neurology clinic in Brazil. J Neurol Neurosurg Psychiatry 1997; 85: 612-616. 17. Singhi PD., Baranwal AK. Single small enhancing computed tomographic lesion in Indian children-I: Evolution of current concepts. J Trop Pediatr 2001; 47: 204-207. 543 Pratibha Singhi and Sunit Singhi 18. Antoniuk SA, Bruck I, Dos Santos LH et al. Seizures associated with calcifications and edema in neurocysticercosis. Pediatr Neurol 2001; 25: 309-311. 19. Sotelo J. Which MRI sequences are best suited to the evaluation of patients with neurocysticercosis? Nat Clin Pract Neurol 2008; 4: 72-73. 20. Garcia HH, Del Brutto OH. Imaging findings in neurocysticercosis. Acta Trop 2003; 87 : 71-78. 21. Jayasundar R, Singh VP, RaghunathanP, Jain K, Banerji AK. Inflammatory granulomas: evaluation with proton MRS. NMR Biomed 1999; 12: 139-144. 22. Govindappa SS, Narayanan JP, Krishnamoorthy VM, Shastry CH, Balasubramaniam A, Krishna SS. Improved detection of intraventricular cysticercal cysts with the use of three-dimensional constructive interference in steady state MR sequences. Am J Neuroradiol 2000; 21 : 679-684. 23. Gupta RK, Prakash M, Mishra AM, Husain M, Prasad KN, Husain N. Role of diffusion weighted imaging in differentiation of intracranial tuberculoma and tuberculous abscess from cysticercus granulomas-a report of more than 100 lesions. Eur J Radiol 2005; 55 : 384-392. 24. 24.Rosas N, Sotelo J, Neito D. ELISA in the diagnosis of neurocysticercosis. Arch Neurol 1986; 43: 353-356. 25. Wilson M, Bryan RT, Fried JA et al. Clinical evaluation of the cysticercosis enzyme linked immunoelectrotransfer blot in patients with neurocysticercosis. J Infect Dis 1991; 164: 1007-1009. 26. Mandal J, Singhi PD, Khandelwal N, Malla N. Evaluation of ELISA and dot blots for the serodiagnosis of neurocysticercosis, in children found to have single or multiple enhancing lesions in computerized tomographic scans of the brain. Ann Trop Med Parasitol 2006; 100 : 39-48. 27. Rodriguez- Canul R, Allan JC, Fletes C et al. Comparative evaluation of purified Taenia solium glycoproteins and crude metacestode extracts by immunoblot for the serodiagnosis of human Taenia Solium cysticercosis. J Clin Diagnostic Lab Immunol. 28. Mandal J, Singhi PD, Khandelwal N, Malla N. Evaluation of lower molecular mass (20-24 kDa) Taenia solium cysticercus antigen fraction by ELISA and dot blot for the serodiagnosis of neurocysticercosis in children. Parasitol Res 2008; 102 : 1097-1101. . 29. Del Brutto OH, Wadia NH, Dumas M et al. Proposal of diagnostic criteria for human cysticercosis and neurocysticercosis. J Neurol Sci 1996; 142: 1-6. 30. Del Brutto OH, Rajshekhar V, White AC et al. Proposed diagnostic criteria for neurocysticercosis. Neurology 2001; 57: 177-183. 31. Rajshekhar V, Haran RP, Prakash S, Chandy MJ. Differentiating solitary small cysticercus grandulomas and tuberculomas in patients with epilepsy- clinical and computerized tomographic criteria. J Neurosurgery 1993; 78: 402-407. 32. Baranwal AK, Singhi P, Singhi S, Khandelwal N. Seizure recurrence in children with focal seizures and single small enhancing computed tomographic lesions. Prognostic Factors on Long-Term follow-Up. J Child Neurol 2001;16: 443-445. 33. Ferreira LS, Zanardi VA, Scotoni AE, Li LM, Guerreiro MM. Childhood epilepsy due to neurocysticercosis: a comparative study. Epilepsia 2001, 42: 1438-1444. 34. Del Brutto AH. Prognostic factors for seizure recurrence after withdrawal of antiepileptic drugs in patients with neurocysticercosis. Neurology 1994; 44: 1706-1709. 35. Garcia H H, Carlton A, W Evans, Nash TE et al. Current Consensus Guidelines for Treatment of neurocysticercosis. Clinical Microbiology Reviews 2002; 15: 747-756. 544 36. Singhi P, Dinakaran, Khandelwal NK. One year versus two years of antiepileptic therapy for SSECTL. J Trop. Pediatr 2003; 5 : 274-278. 37. Singhi PD. Concomitant steroid and albendazole for treating neurocysticercosis. Indian Pediatr 1999; 36 : 1176. 38. Sotelo J, Torres B, Rubio-Donnadieu F, Escobedo F, Rodriquez-Carbajal J. Praziquantel in the treatment of neurocysticercosis: long term follow-up. Neurology 1985; 35: 752-754. 39. Escobedo F, Penagos P, Rodriquez J. Sotelo J. Albendazole therapy for neurocysticercosis. Arch Intern Med 1987; 147: 738-741. 40. Cruz M, Cruz L, Horton J. Albendazole vs praziquantel in the treatment of cerebral cysticercosis: clinical evaluation Trans R Soc Trop Med Hyg 1991; 85: 244-247. 41. Takayanaqui OM, Jardim E. Therapy for neurocysticercosis: comparison between albendazole and praziquantel. Arch Neurol 1992; 49 : 290-294. 42. Baranwal AK, Singhi PD, Khandelwal N, Singhi SC. Albendazole therapy in children with focal seizures and single small enhancing computerized tomographic lesions: a randomized placebo- controlled, double blind trial. Pediatr Infect Dis J 1998; 17: 696-700. 43. Kalra V, Dua T, Kumar V. Efficacy of albendazole and short-course dexamethasone treatment in children with 1 or 2 ring-enhancing lesions of neurocysticercosis: a randomized controlled trial. J Pediatr 2003; 143 : 111-114. 44. Thussu A, Chattopadhyay A, Sawhney IM, Khandelwal N. Albendazole therapy for single small enhancing CT lesions (SSECTL) in the brain in epilepsy. J Neurol Neurosurg Psychiatry 2008; 79 : 238-239. 45. Carpio A, Kelvin EA, Bagiella E, Leslie D, Leon P, Andrews H et al. Ecuadorian Neurocysticercosis Group. Effects of albendazole treatment on neurocysticercosis: a randomised controlled trial. J Neurol Neurosurg Psychiatry 2008; 79:10501055. 46. Padma MV, Behari M, Misra NK, Ahuja N. Albendazole in single CT ring lesions in epilepsy. Neurology 1994; 44: 13441346. 47. Salinas R, Counsell C, Prasad K, Gelband H, Garner P. Treating neurocysticercosis medically: a systematic review of randomized, controlled trials. Trop Med Int Health 1999; 4: 713-718. 48. Salinas R, Prasad K. Drugs for treating neurocysticercosis (tapeworm infection of the brain). Cochrane Database Syst Rev 2007; CD000215. 49. Del Brutto OH, Roos KL, Coffey CS, García HH. Metaanalysis: Cysticidal drugs for neurocysticercosis: albendazole and praziquantel. Ann Intern Med 2006 4;145:43-51. 50. Medina MT, Genton P, Montoya MC et al. Effect of anticysticercal treatment on the prognosis of epilepsy in neurocysticercosis: a pilot trial. Epilepsia 1993; 34: 10241027. 51. Vazquez V, Sotelo J. The course of seizures after treatment for cerebral cysticercosis. N Engl J Med 1992; 327: 696-701. 52. Del Brutto OH. The use of albendazole in patients with single lesions enhanced on contrast CT. N Engl J Med 1993; 328: 356-357. 53. Garcia HH, Gilman RH, Martinez SM, Moulton LH, Del Brutto OH et al. Cysticercosis Working Group in Peru. A trial of antiparasitic treatment to reduce the rate of seizures due to cerebral cysticercosis. N Engl J Med 2004; 15;350:249-258. 54. Das K, Mondal GP, Banerjee M, Mukherjee BB, Singh OP.Role of antiparasitic therapy for seizures and resolution of lesions in neurocysticercosis patients: an 8 year Indian Journal of Pediatrics, Volume 76—May, 2009 Neurocysticercosis in Children randomised study. J Clin Neurosci 2007; 14 : 1172-1177. 55. Jung H, Hurtado M, Medina MT, Sanchez M, Sotelo J. Dexamethasone increases plasma levels of albendazole. J Neurol 1990; 237: 279-280. 56. Vazquez ML, Jung H, Sotelo J. Plasma levels of praziquantel decrease when dexamethasone is given simultaneously. Neurology 1987; 37: 1561-1562. 57. Bittencourt PR, Gracia CM, Martins R et al. Phenytoin and carbamazepine decreased oral bioavailability of praziquantel. Neurology 1992; 42: 492-496. 58. Singhi P, Dayal Devi, Khandelwal N. One week versus four weeks of albendazole therapy for neurocysticercosis in children: a randomized placebo controlled double blind trial. Pediatr Infect Dis J 2003; 22: 268-272. 59. Corral I, Quereda C, Moreno A et al. Intramedullay cysticercosis cured with drug treatment. A case report. Spine 1996; 21 : 2284-2287. 60. Del Brutto OH, Sotelo J, Aquirre R, Diaz Calderon E, Alarcon TA. Albendazole therapy for giant subarachnoid cysticerci. Arch Neurol 1992; 49: 535-538. 61. Proano JV, Madrazo I, Avelar F et al. Medical treatment for neurocysticercosis characterized by giant subarachnoid cysts. N Engl J Med 2001; 345 : 879-885. 62. Pretell EJ, Garcia HH, Custodio N et al. Short regimen of praziquantel in the treatment of single brain enhancing lesions. Clin Neurol Neurosurg 2000, 102: 215-218. 63. Lopez-Gomez M, Castro N, Jung H, Sotelo J, Corona T. Optimization of the single –day praziquantel therapy for neurocysticercosis. Neurology 2001; 57: 1929-1930. 64. Kaur S, Singhi P, Singhi S, Khandelwal N. Combination Therapy of Praziquantal and Albandazole worries Albandazole alone in Children with single Lesion NCC-a randomized placebo controlled double blind trial Ped Infect Indian Journal of Pediatrics, Volume 76—May, 2009 Dis J 2008 – In Press . 65. Nash TE, Singh G, White AG et al. Treatment of neurocysticercosis: current status and future research needs. Neurology 2006; 67: 1120-1127 66. Suri A, Goel RK, Ahmad FU, Vellimana AK, Sharma BS, Mahapatra AK. Transventricular, transaqueductal scopein-scope endoscopic excision of fourth ventricular neurocysticercosis: a series of 13 cases and a review. L Neurosurg Pedaitrics 2008;1:35-39. 67. Goel RK, Ahmad FU, Vellimana AK et al. Endoscopic management of intraventricular neurocysticercosis. J Clin Neurosci 2008 Jul 22. [Epub ahead of print] 68. Singhi PD, Baranwal AK. Single small enhancing computed tomographic lesions in Indian children-II. Clinical features, pathology, radiology and management. J Trop Pediatr 2001; 47: 266-270. 69. Jain S, Padma MV, Kanga U, Mehra NK, Maheshwari NC. Family studies and human leukocyte antigen class II typing in Indian probands with seizures in association with single small enhancing computed tomography lesions. Epilepsia 1999; 40: 232-238. 70. Cruz ME, Davis A, Dixon H, Pawlowski ZS, Proano J. Operational studies on the control of Taenia solium taeniasis/cysticercosis in Ecuador. Bull WHO 1989; 67: 401-407. 71. Sarti E, Schantz PM, Avila G et al. Mass treatment against human taeniasis for the control of cysticercosis: a population-based intervention study. Trans R Soc Trop Med Hyg 2000; 94: 85-89. 72. Gilman RH, Garcia HH. Gonzales AE et al. Metodos para controllar la transmission de la cisticercosis. In Garcia HH, Martinez S, eds. Teniasis/cisticercosis por t. Solium. Lima: Editorial Universo SA, 1996; 327-339. 545