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ORIGINAL ARTICLE
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Hippocampal characteristics among children with calcified neurocysticercosis


1 Department of Radiodiagnosis, Pt B D Sharma Postgraduate Institute of Medical Sciences, Rohtak, Haryana, India
2 Department of Neurology, Pt B D Sharma Postgraduate Institute of Medical Sciences, Rohtak, Haryana, India
3 Department of Pediatrics, Pt B D Sharma Postgraduate Institute of Medical Sciences, Rohtak, Haryana, India

Date of Submission27-Jan-2021
Date of Decision27-Mar-2021
Date of Acceptance23-May-2021
Date of Web Publication11-Oct-2021

Correspondence Address:
Seema Rohilla,
Department of Radiodiagnosis, Pt B D Sharma Postgraduate Institute of Medical Sciences, Rohtak, Haryana.
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpn.JPN_24_21

 

   Abstract 

Aim: The aim of this article is to describe the hippocampal characteristics among children with calcified neurocysticercosis (cNCC). Materials and Methods: This cross-sectional study was conducted among children with epilepsy aged 3–14 years diagnosed with cNCC. Patients showing evidence of cNCC, with prior serial imaging evidence of active NCC, were enrolled. Eligible participants were subjected to magnetic resonance imaging (MRI)-based protocol and sleep-deprived electroencephalography. Hippocampal characteristics on the MRI were described. Results: A total of 31 children with mean (SD) age of 10.3 (3.2) years with cNCC were enrolled in the study. We observed that 42% (13/31) of children with cNCC had borderline (10–20% difference in the volumes of right and left hippocampi) (n = 8) or clear (>20% difference) (n = 5) hippocampal atrophy. Among 31 children with cNCC, 27 (87.1%) had nidus within the lesion and 21 (67.7%) had perilesional gliosis. Conclusion: Children with cNCC are at risk of seizure recurrence on tapering anti-seizure medications. Our study with limited sample size revealed that hippocampal atrophy and perilesional gliosis are prevalent among children with cNCC, predisposing them to the risk of epilepsy.


Keywords: Children, epilepsy, hippocampal atrophy, hippocampal sclerosis, magnetic resonance imaging



How to cite this URL:
Rohilla S, Tyagi S, Bala K, Kaushik JS. Hippocampal characteristics among children with calcified neurocysticercosis. J Pediatr Neurosci [Epub ahead of print] [cited 2021 Dec 9]. Available from: https://www.pediatricneurosciences.com/preprintarticle.asp?id=327898





   Introduction Top


Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system in tropical countries, causing epilepsy. The majority of children with NCC have a well-controlled seizure. In a developing country, apart from prolonged febrile seizures, NCC has been considered to be an initial precipitating factor for the development of hippocampal sclerosis.[1] Studies from Brazil have demonstrated that there was a significant association between calcified NCC (cNCC) and ipsilateral hippocampal sclerosis.[2],[3],[4],[5] It remains an enigma if the association between calcified NCC and hippocampal sclerosis is a mere coincidence or does it have any cause–effect relationship as well.

It is also known that status epilepticus and recurrent seizures often lead to hippocampal damage and subsequent hippocampal sclerosis.[1] Studies reveal an inflammatory process by which NCC triggers the development of hippocampal sclerosis.[2] Ideally, once NCC is treated and is calcified, the seizures should stop, and the patient must achieve seizure remission. However, many children with cNCC may have drug-resistant epilepsy. It was observed that among patients with drug-resistant epilepsy with cNCC, the lesion had significant perilesional gliosis which would have probably contributed to these lesions’ epileptogenicity.[3] This dual existence of cNCC and hippocampal sclerosis is often attributed to refractory seizures among children with cNCC. Majority of studies of this association emanates from Brazil with a paucity of data on Indian children with cNCC.[2],[4],[5],[6],[7] This study was hence designed to describe the hippocampal characteristics among children with cNCC.


   Materials and Methods Top


This cross-sectional study was conducted among children with epilepsy (CWE) aged 3–14 years diagnosed with cNCC attending pediatric neurology clinic of a tertiary care teaching hospital of North India. CWE were defined as those having two or more unprovoked seizures at least 24 h apart. Diagnostic criteria for NCC were as per Del Brutto case definition of NCC.[8] Children with single or multiple calcified lesions whose previous radiological scans revealed evidence of active NCC were included in the study. Children with progressive neurological disease, a chronic systemic illness such as chronic renal failure, chronic liver disease, and those with developmental delay or intellectual disability, were excluded from the study.

A patient information sheet was provided, and written informed consent was obtained from eligible participants. Age at onset of epilepsy, frequency of seizure, seizure-free interval, doses, and antihelminthics duration were recorded. Patients showing evidence of cNCC, with prior serial imaging evidence of active NCC, were enrolled in the study and were subjected to magnetic resonance imaging (MRI)-based protocol and electroencephalography (EEG). A sleep-deprived EEG recording using a 10-20 international electrode system was performed. All MRI investigations were performed on a 3.0 T MR scanner (Discovery MR 750w; GE, OH, USA) using a standard protocol. Thirty-one children were consecutively enrolled for the study. The total number of calcified lesions was studied concerning their number, laterality, lobar distribution, associated gliosis, and nidus (which was seen as hypointensity within hyperintense calcification on filtered phase images of SWAN).

The cNCC lesions were examined for the presence or absence of hippocampal sclerosis, nidus, and perilesional gliosis. Hippocampal atrophy was considered as borderline (10–20%) or clear (>20%) based on the percentage difference between the right and left hippocampi. The measurement of hippocampal volume was semiautomated. The outline of the hippocampus was traced manually in three planes, and once this was done, volume was calculated using this input by readyview software in adw workstation of GE make [Figure 1]. All data were entered in Microsoft Excel. IBM SPSS version 15.0 was used for statistical analysis. Categorical variables were expressed as numbers (percentage), and continuous variables were expressed as mean (standard deviation) or median (interquartile range). Clinical and radiological features were correlated using Spearman’s correlation coefficient.
Figure 1: Image showing volumes of right and left hippocampi

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   Results Top


Clinical characteristics

A total of 31 cases were enrolled. The demographic and seizure characteristics are depicted in [Table 1]. Majority of children had well-controlled seizures [26 (83.8%)]. Few were moderately controlled [1 (3.2%)] or poorly controlled [4 (12.9%)]. Majority of the enrolled children had their last seizure more than a year back [Table 1]. Among the 31 enrolled children with cNCC, 30 (98%) were treated with albendazole for 28 days. Majority of them were vegetarians [19 (61.2%)]. Only two of them had demonstrated focal temporal epileptiform discharges on EEG, and one showed generalized discharges; rest 28 (90.3%) had a normal EEG.
Table 1: Seizure characteristics of children with cNCC (n = 31)

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Radiological findings

Among the 31 children with cNCC, only one child had ipsilateral hippocampal sclerosis [Figure 2]. Thirteen children (41.9%) had either borderline hippocampal atrophy (10–20% difference) [Figure 3] or hippocampal atrophy (more than 20% difference). Of these 13 cases of borderline hippocampal atrophy/atrophy, 8 had cNCC on the same side; 4 had cNCC on the opposite side; and one had cNCC on both the sides [Table 1]. Hippocampal volume among the enrolled children in the age group of 3–6 years (n = 4) was 2.84 (0.16) mm3 on the right side and 2.73 (0.37) mm3 on the left side. Similarly, hippocampal volumes in the age group of 7–14 years (n = 27) were 3.1 (0.58) cumm on the right side and 2.95 (0.66) cumm on the left side. Out of the six cases with highest percentage asymmetry of hippocampal volumes, four showed more T2 values of hippocampi, which were comparatively atrophic.
Figure 2: The neuroimaging of a 14-year-girl with cNCC, who was well controlled on single antiepileptic drug. (A) On NCCT, the lesion appeared uniformly hyperdense, noted in the left parietal region. (B) On phase image extracted from the SWAN imaging, the cyst showed both positive and negative phases consistent with a calcified lesion with scolex. (C) On an axial T2-weighted fluid-attenuated inversion recovery (FLAIR) image, the cyst appeared hypointense without perilesional abnormality. (D) Volumetric image showing right hippocampal volume 2.121 cm3. (E) Left hippocampal volume was 1.217 cm3 suggesting that atrophy as the percentage asymmetry is more than 20%

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Figure 3: Coronal T2W image showing hippocampi (arrows)

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Among 31 children with cNCC, 27 (87.1%) had nidus within the lesion, and 21 (67.7%) had perilesional gliosis. There was no correlation between the seizure frequency and the presence of gliosis in the cNCC. Similarly, there was no significant correlation between the number of calcified lesions and absolute hippocampal volumes. There was no correlation of bilateral hippocampal volume with the presence of nidus or gliosis [Table 2].
Table 2: Correlation between various clinical and radiological characteristics among children with cNCC (n = 31)

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   Discussion Top


The present study found that 42% of the children with cNCC had demonstrated hippocampal atrophy. Majority of the cNCC lesions in the present cohort revealed nidus and perilesional gliosis. There was no correlation between the hippocampal volume and the number of calcified lesions, presence of perilesional gliosis, or presence of nidus within the lesion. Hence, children with cNCC have prevalent epileptogenic focus like hippocampal atrophy and perilesional gliosis.

Hippocampal sclerosis has been reported to be associated with cNCC in a large number of studies.[2],[3],[4],[7],[9-12] The present study showed that only 1 out of 31 children with cNCC had clear evidence of hippocampal sclerosis. It was technically difficult to delineate the exact boundaries of hippocampus in young children. There is no standard cut-off to define hippocampal atrophy in children as normal volumetric standards have not been developed. Hippocampal atrophy was defined as asymmetry of more than 20% between the right and left sides.[13] Using this cut-off, we detected that 42% of our children with cNCC had borderline (10–20%) (n = 8) or clear (>20%) (n = 5) hippocampal atrophy.

In a study from Brazil, it was found that in patients with single cNCC and mesial temporal lobe epilepsy-hippocampal sclerosis (MTLE-HS), the lesion matched the side in which hippocampal sclerosis was observed in 74.1% of the patients.[10] Out of our 13 cases with hippocampal asymmetry, 8 (61.5%) had ipsilateral lesions (out of which 7 had single lesion). Of the four cases with contralateral lesions, atrophy of left hippocampus was seen in three cases. In the fourth case with an equal number of lesions on right as well as left sides, the left hippocampus was atrophic. The study findings were comparable to this Brazilian study. However, in our study, most of the lesions leading to ipsilateral hippocampal atrophy were in frontoparietal lobes, unlike the Brazilian study in which 85% were in temporal lobes.

Presence of perilesional gliosis around the cNCC has been associated with higher seizure frequency and seizure recurrence over 12 months’ follow-up period.[3] As two-thirds of our well-controlled patients demonstrated perilesional gliosis, our study suggested that the isolated presence of perilesional gliosis cannot be considered as a predictor for seizure recurrence among children with cNCC.

The present study had limitations of small sample size, cross-sectional type of study design, and lack of age-matched controls. In the radiological assessment, T2 relaxometry, which would have helped if there is an associated component of mesial temporal sclerosis, was not performed considering the lack of normative age norms for comparison. Moreover, the volumetric measurement of hippocampus was semiautomated which might be prone to few subjective errors and the same is acknowledged. The results of the present study need to be interpreted in the context of this limitation. Further longitudinal studies are recommended with a larger sample size to look for clinical correlation and evolution of hippocampal volumetry with time.


   Conclusion Top


Epileptogenic focus such as hippocampal atrophy and perilesional gliosis is prevalent among Indian children with cNCC. These findings might have implications on the decision of tapering antiepileptic drugs among well-controlled children with cNCC. Further studies with larger sample size and long-term follow-up are suggested.

Author contributions

S. R., K. B., J. S. K.: concept and design of the study; S. T., S. R., J. S. K.: data collection, analysis, and interpretation of data; S. R., J. S. K.: drafting the manuscript and review of literature; J. S. K., S. R., K. B.: critical review of the manuscript for intellectual content and final approval of the version to be published; S. R.: critical review of the manuscript for intellectual content, final approval of the version to be published, and will act as guarantor for the paper. All authors approve the final version.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Yoong M, Martinos MM, Chin RF, Clark CA, Scott RC. Hippocampal volume loss following childhood convulsive status epilepticus is not limited to prolonged febrile seizures. Epilepsia 2013;54:2108-15.  Back to cited text no. 1
    
2.
da Gama CN, Kobayashi E, Li LM, Cendes F. Hippocampal atrophy and neurocysticercosis calcifications. Seizure 2005;14:85-8.  Back to cited text no. 2
    
3.
Souza A de, Nalini A, Kovoor JME, Yeshraj G, Siddalingaiah HS, Thennarasu K. Perilesional gliosis around solitary cerebral parenchymal cysticerci and long-term seizure outcome: A prospective study using serial magnetization transfer imaging. Epilepsia2011;52:1918-27.  Back to cited text no. 3
    
4.
Bianchin MM, Velasco TR, Wichert-Ana L, Alexandre V Jr, Araujo D Jr, dos Santos AC, et al. Characteristics of mesial temporal lobe epilepsy associated with hippocampal sclerosis plus neurocysticercosis. Epilepsy Res 2014;108:1889-95.  Back to cited text no. 4
    
5.
Velasco TR, Zanello PA, Dalmagro CL, Araújo D Jr, Santos AC, Bianchin MM, et al. Calcified cysticercotic lesions and intractable epilepsy: A cross sectional study of 512 patients. J Neurol Neurosurg Psychiatry 2006;77:485-8.  Back to cited text no. 5
    
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Rathore C, Thomas B, Kesavadas C, Abraham M, Radhakrishnan K. Calcified neurocysticercosis lesions and antiepileptic drug-resistant epilepsy: A surgically remediable syndrome? Epilepsia 2013;54:1815-22.  Back to cited text no. 6
    
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Jama-António JMC, Yasuda CL, Cendes F. Neurocysticercosis and hippocampal atrophy: MRI findings and the evolution of viable or calcified cysts in patients with neurocysticercosis. Front Neurol 2019;10:449.  Back to cited text no. 7
    
8.
Del Brutto OH, Nash TE, White AC Jr, Rajshekhar V, Wilkins PP, Singh G, et al. Revised diagnostic criteria for neurocysticercosis. J Neurol Sci 2017;372:202-10.  Back to cited text no. 8
    
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de Oliveira Taveira M, Morita ME, Yasuda CL, Coan AC, Secolin R, da Costa ALC, et al. Neurocysticercotic calcifications and hippocampal sclerosis: A case–control study. PLoS One 2015;10:e0131180.  Back to cited text no. 9
    
10.
Terra-Bustamante VC, Coimbra ER, Rezek KO, Escorsi-Rosset SR, Guarnieri R, Dalmagro CL, et al. Cognitive performance of patients with mesial temporal lobe epilepsy and incidental calcified neurocysticercosis. J Neurol Neurosurg Psychiatry 2005;76:1080-3.  Back to cited text no. 10
    
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Singla M, Singh P, Kaushal S, Bansal R, Singh G. Hippocampal sclerosis in association with neurocysticercosis. Epileptic Disord 2007;9:292-9.  Back to cited text no. 11
    
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Bianchin MM, Velasco TR, Wichert-Ana L, Araújo D Jr, Alexandre V Jr, Scornavacca F, et al. Neuroimaging observations linking neurocysticercosis and mesial temporal lobe epilepsy with hippocampal sclerosis. Epilepsy Res 2015; 116:34-9.  Back to cited text no. 12
    
13.
Sadeghi L, Rizvanov AA, Salafutdinov II, Dabirmanesh B, Sayyah M, Fathollahi Y, et al. Hippocampal asymmetry: Differences in the left and right hippocampus proteome in the rat model of temporal lobe epilepsy. J Proteomics 2017;154:22-9.  Back to cited text no. 13
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2]



 

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