Paediatric parenchymal neurocysticercosis with pleomorphic clinico-radiological presentations: a case series

Abstract

Background

Neurocysticercosis (NCC) is thought to be the most common helminthic infection of central nervous system in India. In children, it has pleomorphic clinical and radiological presentations depending on location and stage of lesion. Solitary cystic granuloma appearing as a single ring enhancing lesion is the most frequently encountered neuroimaging finding in patients with neurocysticercosis or tuberculoma in India. This series reports unusual clinico-radiological aspects of pediatric neurocysticercosis patients of Asian ethnicity.

Case presentation

In the present case series, we have described socio-demographic and clinico-radiological profile of eight cases of neurocysticercosis with parenchymal lesions in varying stages of development. Among these two had single discrete ring enhancing lesion (SDREL), two had single conglomerated ring enhancing lesion (SCREL), and five cases reported to have multiple ring enhancing lesions (MREL). Two cases with recurrent neurocysticercosis have been reported which is quite rare. Magnetic resonance spectroscopy helps to differentiate between neurocysticercosis and tuberculoma and may avoid brain biopsies or unnecessary anti-tubercular treatment. Magnetic resonance spectroscopy (MRS) was done in three cases with findings of absence of lipid peak and choline/creatinine ratio less than 1.2.

Conclusion

Despite the advances in neuroimaging, accurate diagnosis of NCC is still sometimes difficult, which is related to the pleomorphic nature of disease and significant overlapping features with tuberculoma. A combination of proper diagnostic criteria and neuroimaging findings are helpful in making the diagnosis without invasive and potentially harmful investigations in paediatric patients.

Background

Neurocysticercosis (NCC) is the most common acquired infection of central nervous system caused by encysted larva of a cestode- Taenia Solium. Humans are considered definitive host and are infected when they consume raw or undercooked pork or food infected with live cysticerci. It may also spread via feco-oral route or consuming water contaminated with Taenia Solium eggs. World health organisation (WHO) considered cysticercosis as one of the “neglected tropical zoonotic disease” [1]. According to WHO data, 30% of epilepsy cases are in endemic countries and 3% of epilepsy cases globally may be due to NCC [2]. It is considered the most common preventable cause of epilepsy in developing countries. It is a major cause of epilepsy in tropics and the commonest cause of focal seizures in India [3]. NCC is the cause of seizures in about 37% of otherwise healthy children above 3 years of age in India [4]. NCC in children has pleomorphic manifestations depending on the location, number, viability of cyst and host response. Diagnosis of NCC is mainly neuro-radiologic. Sometimes it is challenging to differentiate NCC from tuberculoma, especially in regions where both diseases are endemic and coexist. Magnetic resonance spectroscopy (MRS) is very helpful in differentiating similar looking lesions like tuberculoma, toxoplasmosis, mycosis, small abscesses, brain tumors, and even vascular malformations [5]. The management of NCC mainly includes antihelminthics, antiepileptics and corticosteroids. Many aspects related to diagnosis and treatment of NCC in children remain poorly understood despite advancing knowledge. Through this case series we are describing the pleomorphic clinical and radiological presentations of NCC in pediatric age group and also the role of MRS in diagnosing those patients.

Case presentation

This case series describes eight children with NCC: five were males and three were females. All the identifiers for the cases were removed to maintain participant anonymity. Informed consents/assent were taken from the guardians/parents of the participants. The age of first presentation ranged from 5 to 12 years. All children were of Asian ethnicity and Hindu by religion except one who was Muslim (case 1). With regard to eating habits all of them reported that they washed the eatables (fruits and vegetables) prior to consuming. Four cases used ground water and rest used municipal water supply for drinking. All cases had garbage disposal except one who disposed waste directly into drain (case 8). All cases had toilet facilities at home. Case 1 reported to have pigs around his household. None of the cases reported to have slaughter house near their premises. The frequency of consuming non-vegetarian food varied from once a week to once a month among all the cases. None of the cases reported to consume pork as non-vegetarian food. Socio-demographic characteristics are shown in Table 1.

Table 1 Socio-demographic characteristics of the cases

All cases had focal seizures as the presenting symptom. Other associated symptoms were headache, loss of consciousness (in 3 cases each) and one (case7) had vomiting. None of the cases in this series had visual disturbances, neurological deficit, midline shift or hydrocephalous. Six cases (1, 3, 5, 6, 7, and 8) received sodium valproate as first line antiseizure medication (ASM) and two received phenytoin. Case 2 developed phenytoin toxicity after receiving it for 2 years and presented in outpatient department (OPD) with headache and ataxia. Serum phenytoin levels were 42 mg/l and brain MRI done was normal. Phenytoin was stopped and the patient was managed conservatively. The patient showed gradual improvement in headache by day two while ataxia improved by day 7. Two cases (3 and 4) reported to have recurrent NCC. No case reported to have break through seizures. None of the cases required antiseizure polytherapy for seizure control. Overall compliance was good except case 3 (loss to follow-up). All the cases of this series received Albendazole (dose 15 mg/kg/day) as antihelminthic therapy for 28 days. All cases used steroid for treatment. The duration of corticosteroids used varied from 5 to 14 days. Only case 3 reported to have received some traditional medicine. Table 2 shows the details of the clinical profile of the cases.

Table 2 Clinical profile of cases

Magnetic resonance imaging (MRI) was done for neuroimaging details for all the cases. Out of total eight cases, five cases as shown in Figs. 1, 2, 3, 4 and 6 had multiple lesions of NCC. Of these two had single conglomerated ring enhancing lesions (SCREL) as shown in Figs. 3 and 4. Three cases had single discrete ring enhancing legions (SDREL) as shown in Figs. 5, 7 and 8. The commonest location of NCC lesions in brain parenchyma was parietal and parieto-occipital region. Varying stages of NCC such as colloidal-vesicular, granulo-nodular, and calcified nodular with perilesional oedema were seen. No case was reported to have hydrocephalus, midline shift and lepto-meningeal enhancement on MRI brain. MRS was done for three cases shown in Figs. 6, 7 and 8 to differentiate NCC from tuberculoma with findings of absence of lipid peak and choline/creatinine ratio less than 1.2. Table 3 depicts details of investigations and neuroimaging findings of all the cases.

Fig. 1

T1 (A, D) and T2 (B, C) showing multiple cysts in colloid-vesicular stage cyst with extensive perilesional oedema in left parieto-occipital lobe

Fig. 2

FLAIR (A), T2 (B, C) shows multiple hypo intense cysts of NCC in granular-nodular stage with some perilesional oedema

Fig. 3

T2 (A, D) and FLAIR (B) images showing two cysts in colloid-vesicular stage in parietal lobe with perilesional oedema. CISS (constructive interference in steady state) sequence (C) show conglomerated lesions with perilesional oedema

Fig. 4

Conglomerated cyst seen on T2 (A) and CISS (B) images (blue arrow). Two calcified nodular stage cyst of NCC seen as hypointense cyst on FLAIR (C, E) and T2 (D) in right frontal and parietal lobe. Single cyst in colloid vesicular stage NCC seen with perilesional oedema on T2 (F) in right parietal lobe

Fig. 5

T2 (A), FLAIR (B) and CISS sequence (C) shows solitary cysticercal lesion in occipital lobe in vesicular nodular stage with perilesional oedema

Fig. 6

 T2 (A, C) and FLAIR (C, D) shows two lesions in frontal and parieto-occipital lobes. Scolex clearly visible in T2 (A) and FLAIR (B) suggestive of NCC. Magnetic resonance spectroscopy (E) shows NAA peak (red arrow) and Cho:Cr (choline:creatine) = 1.1. Cr (green arrow) and Cho (yellow arrow) peaks are also seen  

Fig. 7

T2 (A), T2 (B), FLAIR (C) and contrast images (D) show single parieto-occipital cyst with central hypointense scolex suggestive of lesion in colloid vesicular stage of NCC with surrounding oedema. Magnetic resonance spectroscopy (E) shows an absence of lipid peak (white arrow) and Cho:Cr (choline: creatine) = 0.89. NAA (red arrow), Cr (green arrow), and Cho (yellow arrow) peaks are also seen

Fig. 8

FLAIR (A) and T2 (B) images show single lesion in granular nodular stage of NCC in the occipital lobe. Magnetic resonance spectroscopy (C) shows an absence of Lipid peak (white arrow) and Cho:Cr = 0.62. NAA (red arrow), Cr (green arrow), and Cho (yellow arrow) peaks are also seen

Table 3 Investigations and radiological profile of cases

Cases 1 to 8 are shown in following description and their corresponding Figures are respectively shown below with their descriptions.

Discussion

Cysticercosis is caused by ingestion of Taenia solium. In the intestinal tract of human host its eggs release the encysted larvae (oncospheres). These oncospheres penetrate the intestinal wall, enters the blood stream then are transported and deposited to various tissues of the body including brain, eyes, skin, and muscle. In these tissues oncospheres differentiate into metacestodes which further develop into cysticerci. In NCC, the brain parenchyma is most commonly infested with high rates of deposition at grey-white matter junction. It may be due to accumulation of metacestodes in small terminal blood vessels [6]. Most lesions are single ring enhancing lesion (SREL) or multiple ring enhancing lesion (MREL) in different stages of evolution [7]. Cystecerci of Taenia solium undergo four stages of involution in brain parenchyma. First stage is vesicular stage, showing cyst with translucent walls and viable scolex followed by colloidal stage characterised by cyst with a thick wall. Third stage is granular stage showing cyst with thicker wall and degenerated scolex. Final stage is calcification stage in which cyst develops into calcified nodule [8].

Clinical features of NCC vary widely in children and continue to pose a challenge in clinical practice. Most common symptoms are focal seizures, generalised seizures, neurological deficit and signs of raised intracranial pressure. In this series, all cases had focal seizures as primary manifestation of the disease. A study of 500 children with NCC in India reported that 95% of cases had seizures, of these 84% cases had focal seizures, 30% children showed symptoms of increased intracranial pressure, and 4% showed neurological deficit [9]. In this series, none of the cases reported to have increased intracranial pressure, neurological deficit or visual disturbances.

Neuroimaging showed five cases in colloidal-vesicular stage, two cases in granular-nodular stage, and one in calcified nodular stage in brain parenchyma. Conglomerated lesions were thought to be unusual in NCC but were commonly reported as neurotuberculosis [10]. In the present series two cases were identified to have single conglomerated ring enhancing lesion (SCREL). Conglomerated ring enhancing lesions are best seen on MRI due to its better soft tissue resolution and multiplanar capabilities. Rajshekhar et al. [11] described atypical” type B” lesions having two confluent discs or rings or a combination in 4 out of 25 and 5 out of 43 biopsy proven cases of NCC. Recently Kumar et al. [12] reported “atypical” lesion having bilobed, septate or disc configurations in 28.8% of cases on MRI. These atypical lesions often persist unresolved for a longer period and may even be associated with a higher risk of seizure recurrence because of persistence of calcified focus.

Out of eight NCC cases, three had SDREL with perilesional oedema. The commonest neuroimaging finding of NCC is “single small ring enhancing lesion”- a single lesion, < 20 mm with perilesional oedema. These solitary lesions usually resolve during treatment between few weeks to one year whereas conglomerated lesions takes longer time to resolve [13]. Reappearance of NCC at the same site after documented resolution has been sparsely described. We have reported two cases with recurrent NCC both having recurrent lesion at different locations after 2.5 and 2 years interval. Singh et al. [14] reported four cases of reappearing CT lesions; two at the same and two at different locations. It was postulated that recurrent lesions at the same location are secondary to co-localisation of a multiple stream of cysts or viable meta-cestode larvae in a particular brain region which appear and become active at different times, whereas recurrent lesions in different locations are secondary to recurrent auto infections in taeniid carriers. Kumar et al. [12] described three cases of recurrent symptomatic solitary NCC at a location different from initial site after 2.5, 4, and 7.5 years interval. The reason given was that all new granulomas resulted from reinfection rather than persistent of initial infection. VDe Souza et al. [15] described natural history of NCC in 81 patients on serial MRI over 24 months and did not report a single recurrence of NCC. In an MR-based prospective study, Kumar N et al. [16] evaluated natural course of 59 cases of single conglomerated granuloma (SCG) over 3 years without any antihelminthics or steroid treatment and did not report a single case of recurrent granuloma.

All cases in this series received antihelminthic therapy as Albendazole (15 mg/kg/day) for 28 days and corticosteroids for 5–14 days. Singhi et al. [9] reported new lesions in around 4% of NCC patients during long term clinical and radiological follow up in 500 children with parenchymal NCC.

There are no clear guidelines for management and diagnosis of paediatric NCC. A recent meta-analysis involving 16 trials and another involving 15 trials have concluded that Albendazole was effective in early resolution and radiological clearance of lesions and also preventing seizures [17, 18]. Corticosteroids are administered to reduce host inflammatory reaction and increase level of Albendazole sulfoxide in plasma [19]. Antiseizure medication (ASM) used to treat NCC are similar to those used for other seizure disorders. In our series six cases received sodium valproate and two received phenytoin.

Case 2 in this series presented with ataxia and headache as manifestations of acute phenytoin toxicity at serum phenytoin levels of 42 mg/L. Acute phenytoin toxicity manifests as nystagmus (95%), ataxia (88%), lethargy and seizures. Ataxia usually precedes nystagmus in children. Phenytoin levels > 30 mg/L may cause side effects as ataxia, dysarthria, and seizure. Somnolence is often seen at serum phenytoin levels > 40 mg/L [20].

MRS was done for three cases in this series to differentiate between NCC and tuberculoma. Case 6 shows N-acetyl aspartate (NAA) peak, Cho/Cr (choline: creatine) = 0.62 and absence of lipid peak. Case 7 had NAA peak and Cho/Cr = 0.89 with absence of lipid peak. In case 8 there was NAA peak and absence of lipid peak with choline/Cr = 1.1. The presence of a high lipid peak and an increased choline/creatine ratio were seen consistently with tuberculoma. Lipid peak may be attributed to the presence of large lipid fraction in Mycobacterium tuberculosis and the increase in choline/creatine ratio is probably due to damage to brain tissue, which is minimal in NCC [21]. MRI and MRS features differentiating NCC from tuberculoma are shown in Table 4 [22, 23].

Table 4 MRI and MRS features differentiating NCC from tuberculoma [22, 23]

Conclusion

Despite the advances in neuroimaging, accurate diagnosis of NCC is still sometimes difficult, which is related to the pleomorphic nature of disease and significant overlapping features with tuberculoma. A combination of proper diagnostic criteria and neuroimaging (MRI/MRS) findings are helpful in making the diagnosis without invasive and potentially harmful investigations in paediatric patients.