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Hippocampal characteristics among children with calcified neurocysticercosis
Seema Rohilla1, Shristi Tyagi1, Kiran Bala2, Jaya Shankar Kaushik3
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 Submission||27-Jan-2021|
|Date of Decision||27-Mar-2021|
|Date of Acceptance||23-May-2021|
|Date of Web Publication||11-Oct-2021|
Department of Radiodiagnosis, Pt B D Sharma Postgraduate Institute of Medical Sciences, Rohtak, Haryana.
Source of Support: None, Conflict of Interest: None
| 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
| Introduction|| |
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. Studies from Brazil have demonstrated that there was a significant association between calcified NCC (cNCC) and ipsilateral hippocampal sclerosis.,,, 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. Studies reveal an inflammatory process by which NCC triggers the development of hippocampal sclerosis. 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. 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.,,,, This study was hence designed to describe the hippocampal characteristics among children with cNCC.
| Materials and Methods|| |
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. 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.
| Results|| |
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.
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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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|| |
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.,,,,[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. 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. 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. 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|| |
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.
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
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]