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ORIGINAL ARTICLE
Year : 2021  |  Volume : 69  |  Issue : 2  |  Page : 385-391

Recurrent Neurocysticercosis: Not So Rare


1 Department of Neuroimaging and Interventional Neuroradiology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Neurology, All India Institute of Medical Sciences, New Delhi, India

Date of Submission05-Feb-2020
Date of Decision07-Aug-2020
Date of Acceptance27-Jan-2021
Date of Web Publication24-Apr-2021

Correspondence Address:
Ajay Garg
Department of Neuroimaging and Interventional Neuroradiology, Room No 12, Cathlab Complex, Neurosciences Centre, All India Institute of Medical Sciences, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.314519

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 » Abstract 


Background:
Solitary cysticercus granuloma (SCG) appearing as a single ring-enhancing lesion (SREL) is the most frequently encountered imaging finding in patients of neurocysticercosis (NCC) in India and during follow-up, most of SCGs resolve with or without calcifications. Recurrent SCG have been rarely reported.
Objectives:
The aim of our study is to report the incidence of recurrent SCG in a cohort of patients with SCG and postulate the hypothesis.
Materials and methods:
This retrospective study included 278 patients with SCG meeting the criteria of NCC. Their medical records and imaging studies were analyzed.
Results:
Out of 278 patients, 119 patients with SCG meeting the criteria of NCC with follow-up imaging were included. 15 (12.61%) had recurrent NCC and 104 (87.4%) patients did not have any recurrence during a median follow-up of 14.23 months (range; 0.24 - 113.3) and 25.26 months (range; 3.09- 98.11) respectively. Out of 15 recurrent NCC cases, ten patients had documented imaging resolution or partial regression of previous lesion followed by occurrence of new SCG in the same location, three patients had change in morphology of lesion from solitary discrete REL to solitary conglomerate REL secondary to development of new cysticercus granuloma adjacent to old lesion patients had recurrent lesions adjacent to previous lesion and two patients had new SCG in different locations following regression of old SCGs.
Conclusion:
Recurrent SCGs are not uncommon in NCC and recurrence is more likely to occur at the site of initial infection and therefore may be mistaken for persistent infection or other granulomatous lesions.


Keywords: Neurocysticercosis, Solitary cysticercus granuloma (SCG), Single ring-enhancing lesions, Recurrent NCC, Conglomerate ring-enhancing lesions, Enlarging NCC
Key Message: Recurrent NCC is not rare and is most likely to occur at the site of initial infection. It should not be mistaken for other granulomatous infection like neurotuberculosis.


How to cite this article:
Kaur KP, Garg A, Devaranjan Sebastian LJ, Bhatia R, Singh MB, Srivastava A, Tripathi M, Padma M V. Recurrent Neurocysticercosis: Not So Rare. Neurol India 2021;69:385-91

How to cite this URL:
Kaur KP, Garg A, Devaranjan Sebastian LJ, Bhatia R, Singh MB, Srivastava A, Tripathi M, Padma M V. Recurrent Neurocysticercosis: Not So Rare. Neurol India [serial online] 2021 [cited 2021 May 10];69:385-91. Available from: https://www.neurologyindia.com/text.asp?2021/69/2/385/314519




Neurocysticercosis (NCC) is a common intracranial parasitic infection caused by larval stage of Taenia solium. Advances in imaging techniques, including computed tomography (CT) and magnetic resonance imaging (MRI), delineate the number and morphological characteristics of the lesions, their stage of evolution, and the degree of edema; and have facilitated a reliable way of diagnosis and management of NCC.[1],[2],[3] Solitary cycticercal granuloma (SCG) appearing as a single ring-enhancing lesion (SREL), either discrete (SDREL; Type A lesion) or conglomerate (SCREL; Type B lesion), is the most frequently encountered radiological finding in patients of NCC in India.[4],[5],[6] Treatment of SCG is controversial: Ranging from no treatment[7] to treatment with antihelminthics,[8] antiepileptics[9],[10] steroids in isolation or in various combinations. During follow-up, most of the SCGs resolve with or without calcifications.[9],[10],[11],[12] Rarely SCG may increase in size or undergo a change in configuration from SDREL lesion to SCREL.[13],[14] Furthermore, there are isolated case reports of new SCGs during follow-up.[15],[16],[17],[18] When these new lesions appear in the same locations, they may be misread as the persistent previous lesion. Similarly, when the SCG morphology change from SDREL (type A) to SCREL (type B) or new SCG appears, they may be mistaken for other diseases like neurotuberculoma or re-infection with NCC especially in Indian subcontinent.

The exact incidence and pathogenesis of these recurrent SCGs has not been defined. In this retrospective analysis, past 10-year medical records of patients with SCG meeting the diagnostic criteria of NCC were evaluated for new lesions during follow-up.


 » Material and Methods Top


Study design and settings

In this retrospective study, patients with diagnosis of cysticercosis based on the revised diagnostic criteria for NCC proposed by Rajshekhar et al.[19] and for whom CT/MRI examinations were archived in departmental PACS database were included. The study was approved by the institutional ethics committee. Medical records of these patients were reviewed for clinical presentation and treatment history.

Patients whose CT/MRI examinations revealed only calcified lesions or enhancing disc lesions, patients with multiple lesions in more than one location and patients who had received anti-tubercular treatment were excluded from further analysis.

Imaging evaluation: Baseline

The baseline CT/MRI scans of patients were evaluated for presence of scolex which was defined as eccentric hyperdensity on CT and/or hypointensity on T2-weighted image in MRI and presence of conglomeration. The SCGs were further classified as single discrete ring-enhancing lesions (SDRELs) when a well-defined lesion was seen and single conglomerate ring-enhancing lesions (SCRELs) when two or more ring lesions, or ring/rings plus disc lesions were present touching one-another. Amongst SCRELs, the size and core of the largest ring lesion was evaluated.

Imaging evaluation: Follow-up

Follow-up imaging scans were evaluated for change in morphology and resolution of lesions and surrounding edema. The lesions were considered 'resolved' if the follow-up CT/MRI study did not show the lesion. Lesions were defined as “enlarging” SCG when there is increase in size of SREL during follow-up. Recurrent lesion was defined as a lesion which either disappears and appears again, change in morphology of the lesion from SDREL to SCREL or new lesion appears at same or different location. Persistence of the lesion was defined as evidence of residual lesion in CT/MRI scan (with or without contrast) and then, size of the lesion and degree of perilesional edema were compared with previous scans.

Statistical analysis

Statistical analysis was performed using Stata version 13.0. Comparisons between the recurrent NCC and no recurrence groups were carried out using independent sample t test for continuous variables and Chi-square tests for categorical variables. A value of P < 0.05 was considered significant.


 » Results Top


Records of 278 patients of SCG meeting the criteria of NCC were retrieved from the department PACS database. As treatment history was not available for 85 patients, they were excluded from further analysis. Of the remaining 193 patients, 31 received anti-tubercular treatment, and in 43 patients, follow-up imaging was not done and therefore, these were also excluded. Finally, 119 patients with SCGs meeting the criteria of NCC were included in this study [Figure 1].
Figure 1: Study flow diagram

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Figure 2: Baseline axial FLAIR (a) and CECT after 5 months (b) show a SDREL with eccentric hyperintensity in pons. Repeat CECT (c) after 6 months showed conversion of SDREL to SCREL with increased edema and mass effect. FU Axial Flair (d) shows conglomerate ring lesions with edema in pons. Axial CECT (e) shows a SDREL (arrow in e) in left frontal region, which evolves into SCREL after 3 years (arrow in f) and 2 calcified disc lesions (arrowhead in g) after another 2.3 years. Coronal contrast- enhanced T1-WI (h) shows a SDREL in left parietal lobe which evolves into SCREL after 10 months (arrow in i)

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Figure 3: CECT (a) shows SDREL with eccentric scolex, repeat CT (b) and fused CT scan (c) scan shows new lesion in the same region. CECT (d) shows a SDREL with eccentric scolex, repeat CECT (e) shows 2 conglomerate RELs in same location. Another CECT (f) shows 2 conglomerate ring lesions with perilesional edema. CECT (g) showed SDREL, which resolved in CT (h) followed by a SDREL in the same region (i). Baseline CECT (j) and CECT done after 1 month (k) show a SCREL. Repeat CECT (l) show 2 RELs of different morphology in the same region

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Figure 4: CECT (a) shows a SDREL with eccentric scolex (arrow in a) with perilesional edema. CECT (b) shows significant reduction in size of previous lesion (arrow in b) and new REL with scolex (arrowhead in b) lateral to previous lesion. Coronal FLAIR (c and d) MRI scans done 34 months apart show single discrete ring lesions with eccentric scolices with different morphology. CECT (e and f) done 23 months apart show ring lesions of different morphology in right medial frontal lobe. Reconstructed coronal CECT scans (g and h) done 4 months apart show ring lesions of different morphology in left parietal lobes

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Figure 5: Axial T2 (a), FLAIR (b) and post contrast T1-WI (c) show a SCREL; the core of the posterior lesion is bright on T2WI (a) and shows signal suppression on FLAIR (b) with eccentric hyperintense scolex. Follow-up NCCT after 3.5 months shows reduction in lesion size and resolution of edema (d). Interval MRI after 18 months: Axial T2 (e), FLAIR (f) and contrast enhanced T1WI (g) shows a thick walled REL with eccentric scolex in same location and the new lesion had different morphology than the previous one. Follow-up NCCT after 6 months (h) shows resolution of edema and lesion

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Out of 119 patients, 15 (12.6%) had recurrent NCC and 104 (87.4%) patients did not have any recurrence during a median follow-up of 14.23 months (range; 0.24–113.3) and 25.26 months (range; 3.09–98.11) respectively. The patients with recurrent NCC had a median age of 19 years (age range 10 to 46 years), and 8 (53.3%) were males, whereas patients without recurrent NCC had a median age of 22 years (age range 6 to 61 years), and 31 (29.8%) were males [Table 1].
Table 1: Demographic and Clinical profile

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Baseline imaging

In recurrent NCC group, the original lesion morphology was SCREL in 8 (53.33%) and SDREL in 7 (46.67%) patients, whereas lesion morphology in nonrecurrent group was SCREL in 63 (60.58%) and SDREL in 41 (39.42%) patients [Table 1].

The most common clinical presentation in both groups was seizure followed by headache [Table 1]. The clinical presentation and treatment history of the patients have been summarized in [Table 1].

Follow-up imaging

Follow-up imaging scans were done in patients as and when they reported to hospital for follow-up at different time-points which were not comparable. The clinical indication of follow-up imaging was recurrent seizures in 8 patients, headaches with seizures, headaches with vomitings, and hemisensory loss in 1 patient each. In the remaining 4 patients, recurrent lesion was an incidental finding during routine follow-up imaging [Table 2].
Table 2: Recurrent NCC cases with details

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Recurrent NCC

Three patients had change in morphology of lesion from SDREL to SCREL secondary to development of new cysticercal granuloma adjacent to old lesion during median follow-up interval of 10.2 months (range 6.9-38.06 months). Ten patients had documented imaging resolution or partial regression of previous lesion followed by occurrence of new SCG in the same location after median follow-up time of 23.6 months (range 3.9–98.4 months). Two patients had new SCG in different locations following regression of old SCGs [Table 2].

Follow-up imaging of recurrent lesion was available in nine patients. The recurrent lesion had completely resolved without calcification in 1 patient, partially/completely calcified in 2, reduced in size along with reduced perilesional edema in four patients, and persisted in original size with reduced perilesional edema only in two patients [Table 2].


 » Discussion Top


Solitary cycticercal granuloma (SCG) appearing as a single discrete enhancing lesions (SDELs) is the most frequent imaging presentation of NCC in India unlike patients from Latin America and Africa[4],[6] in whom multilesional presentation is common. The viable cysts are rarely seen in a minority of patients with heavy parasite load. With the advent of multi-slice CT and thin-slice image acquisition, multiple conglomerate ring lesions in a single location known as single-conglomerate ring lesions (SCRELs) are increasingly being recognized in neurocysticercosis.[5] SDRELs usually resolve during treatment between few weeks to an year[10],[18],[20],[21] whereas SCRELs, also known as atypical NCC or Type B lesions,[22] usually take longer to resolve as compared to SDRELs.[10] Furthermore, most SCGs have been reported to have disappeared or regressed spontaneously[7] or when treated with anticonvulsant drugs alone.[21]

Reappearance of an NCC at the same site after documented “resolution” has been sparsely described till date.[15],[16],[17],[18] Singh G, et al.[17] reported four cases of reappearing CT lesions; two at the same and two at different locations. They postulated that recurrent lesions in the same location are secondary to co-localization of a multiple stream of cysts or viable metacestode larvae in a particular brain lesion which appears or become active at different times, whereas recurrent lesions in different locations are secondary to recurrent autoinfection in taeniid carriers.[17] Kumar S. et al.[18] described 3 cases of recurrent symptomatic solitary NCC at a location different from the initial site after intervals of 2.5, 4, and 7.5 years respectively and postulated that all new granulomas resulted from reinfection rather than persistence of initial infection.

Change in morphology of SCG from SDREL (type A) to SCREL (type B lesion) has been previously reported in few case reports in asymptomatic patients during routine follow-up of 6–12 weeks[13],[14] and has been attributed to sequential development of cysticercal cyst deposited with the original cyst. Interesting, in the present series, all 3 patients demonstrating conversion of morphology of SCG from SDREL to SCREL were symptomatic with longer median follow-up interval of 10.2 months. We have included these cases as recurrent SCGs and not as enlarging SCGs as their pathogenesis appears to same as other recurrent NCC. After metacestodes deposition in the brain via hematogenous route; when one cyst mature, we get SDREL; when multiple cysts mature at the same time, we get SCREL and when other cysts mature early following maturation of single cyst, morphology of SCG change from SDREL to SCREL. On the other hand, when these cysts remain dormant and mature at different time-points following resolution of previous cyst, new neurocysticercal lesions develop at the same location. This is in line with the hypothesis proposed by Singh G, et al.[17] Kumar S, et al.[18] suggested that another possibility of recurrent in the same location could be related to vascular architecture in an individual patient as the larvae spread to the brain through the hematogenous route. On the other hand, enlarging SCG appears as a uniform increase in the size of the lesion but no alteration in its original shape and is possibly due to increasing inflammation around the cyst and its subsequent organization.[14]

This study is the largest cohort of recurrent NCC wherein the recurrent lesions mostly occurred at the same location, either as change in morphology from SDREL to SCREL lesions or new lesion following complete or partial regression of previous lesion. Differentiation of recurrent lesion from the persistent lesion is helpful in management with AEDs as the seizure outcome for an SCG is very good after the resolution of the granuloma and tapering of AEDs.[23] Recurrent NCC lesions are likely to be mistaken for persistent lesions, which may be other granulomatous lesions like neurotuberculoma. These recurrent NCC in the same location cannot be explained by a possible 'miss' or 'false positive' diagnosis of “disappearance” of the granuloma due to poor resolution of the interval CT scan, since we acquired all follow-up CECT scans on a multi-slice CT scanner with a slice thickness of 2 mm. In our cases, recurrent NCC occurred within 3 years and lesions were more commonly within the same location so persistence of initial infection is more likely cause of new lesions in our study.

In our study, recurrent NCC lesions were 12.61% patients (15/119), which is high compared to existing literature. In an MR-based prospective study, Kumar et al.[9] evaluated natural course of 59 cases of SCG over 3 years without any anti-helminthic or steroid treatment and did not report a single case of recurrent granuloma. Similarly de Souza et al.[24] described natural history of NCC in 81 patients on serial MRI over 24 months and didn't report a single case of recurrent NCC. Singhi P, et al.[25] reported new lesions in about 4% of NCC patients during long-term (mean 8 years, range: 5–17 years) clinical and radiological follow-up in 500 children with parenchymal NCC; however, the location of new lesions in relation to the previous lesion is not mentioned. The reason for high incidence of recurrent NCC in our study could be due to selection bias as our center is a tertiary care hospital with a large referral base.

If the recurrent lesion in the same location is due to persistence of initial infection in the form of dormant cysts, is there any role of antihelminthic treatment to prevent recurrent NCC? Singh G proposed that it may be worthwhile to consider albendazole therapy in SCG with the intention of treating the active co-localized cyst.[17] We didn't find any statistically significant difference between recurrent and non-recurrent group regarding efficacy of treatment in preventing recurrence. However, a prospective study with large sample size is required to address this question.

Our study has certain limitations. Similar to the previous studies' histopathological confirmation of imaging diagnosis of NCC was not available as no lesion was excised surgically. However, the diagnosis of NCC was made on the basis of established criteria in the current study.[19] Another potential shortcoming is the retrospective nature of the study which may cause selection bias. Like other retrospective studies, imaging in this study was done at variable time-points, and therefore, imaging interval between baseline and follow-up imaging is not uniform. A significant number of patients in our study cohort with imaging findings suggestive of NCC had received antitubercular therapy and were, therefore, excluded from the analysis. In addition, our center is a tertiary referral center and most of the cases were referred as persistent granulomas leading to selection bias.


 » Conclusion Top


In conclusion, the present study demonstrates that recurrent SCG is not rare in NCC and recurrence is more likely to occur at the site of initial infection. Recurrent NCC lesions should not be mistaken for other granulomatous lesions like tuberculoma requiring change of treatment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

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Singh MK, Garg RK, Nath G, Verma DN, Misra S. Single small enhancing computed tomographic (CT) lesions in Indian patients with new-onset seizures. A prospective follow-up in 75 patients. Seizure 2001;10:573-8.  Back to cited text no. 10
    
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    Figures

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