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:
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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
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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 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
