Complex neurocysticercosis lesions on imaging: Explained through correlative histomorphology

Abstract

Objectives

Neurocysticercosis, the commonest neuro-parasite, sometimes presents as complex ring enhancing lesion causing diagnostic dilemma. We aim to establish radio-histo-morphological equivalents of early events in degeneration of the parasite to explain such imaging phenotypes.

Methods

We compared patterns of degeneration in 23 randomly selected complex NCC on MRI with histo-morphology in 30 cysts obtained from an unrelated post mortem brain.

Results

The anatomy of the parasite and the degenerative patterns of the scolex (hydropic changes, calcification, evagination, and fragmentation) and the cyst wall (undulation, accessory loculi, and frank disruption) were well demonstrated on both. The intact scolex remarkably resembled head of intestinal Taenia. The complex lesions were conglomeration of multiple communicating cysts with a single parent cyst and multiple daughter cysts. The parent cysts contained a solitary variably degenerated scolex, had thicker walls and associated chronic inflammation. The remaining cysts of the lesion complex contained no scolex, had poorly organized walls, turbid contents, and florid perilesional enhancement with leakage of contrast. Three lesions assumed a multi-cystic pseudo-tumorous pattern, of which two resolved into solitary calcific remnants on follow up.

Conclusion

Complex lesion in NCC result from degeneration of solitary parasite with perilesional gliosis, surrounded by multiple non-larval daughter cysts inciting acute intra and perilesional inflammation due to enhanced antigenic challenge. Possibly, attempted abortive asexual reproduction by the cellulose cyst as a preterminal event results in a “limited Racemose like transition.” Correct interpretation has diagnostic and therapeutic implications as active lesions and their fibrocalcific residue may have greater epileptogenic potential.

Introduction

Neurocysticercosis (NCC) is caused by larva of Taenia solium, and is the commonest cause of new onset seizures in developing countries. The usual imaging phenotype is a solitary cysticercus granuloma (SCG), comprising two third of all patients.^1–6 Tuberculosis of the brain is also common in these areas and similarly presents as a solitary ring enhancing lesion (REL). There are signature clinical and imaging signs to differentiate the two.^6,7 Demonstration of scolex in a cystic lesion smaller than 2 cm is diagnostic of vesicular NCC. Degeneration of the parasite into colloidal, granulo-nodular and calcified stages are widely accepted, yet imaging may not be conclusive in all cases.^7–9

Another, diagnostic dilemma arises when NCC presents as solitary large volume conglomerated or “multi cystic tumorous lesion.” The parasite may also change morphology and paradoxically increase in size spontaneously or following cysticidal treatment. We frequently encounter such atypical phenotype in solitary NCC and other centers have similar experience.^10–12 Apart from tuberculosis, such morphology also needs exclusion of other possibilities like non-tubercular infections, demyelination and more importantly tumors.^10–15 This may cause delay in starting or disruption of ongoing cysticidal treatment, initiation of anti-tubercular treatment (ATT) or even lead to brain biopsy to rule out a neoplasm. ¹²

There is scanty literature on early degenerative changes in the parasite, specifically in description of radio-histopathological equivalents, as lesion resection is seldom performed. Early pathological changes, particularly during parasites transition from vesicular to colloidal stage can explain such lesions. In this study, we have tried to decipher such atypical presentations of NCC, through correlative radiological and histopathological patterns.

Material and methods

Imaging

After obtaining approval from institutional ethics committee, in this retrospective observational study, we analyzed 23 randomly selected patients, with documented solitary complex NCC on MRI (age range 10–52 years, 12 males, 11 females). The diagnosis was based on consensus guidelines, factoring in local endemicity, newly acquired seizures, visible scolex within cystic REL, exclusion of other co-morbidities, and response to anti-helminthic treatment. The analyzed sequences were T2 FSE, FLAIR, T1 FSE/MPRAGE (before and after contrast), DWI, SWI, and high resolution 3D T2 sequences using CISS or SPACE (Siemens, Erlangen, Germany). The cysts were evaluated for size, number, perilesional edema, and external morphology (shape, outline, undulations or discontinuity of wall, accessory cysts and their intercommunications). The intra-cystic structures were studied for scolex recognized as focal hypo intensity on T2WI and SWI, or calcification on CT scans. The number, location, integrity, and hydropic changes in the scolex were observed. Wherever available, serial evolution of cyst morphology was observed for any pattern. Seven patients were already on cysticidal treatment at the time of imaging and one on ATT.

Histopathology

The histological sections were prepared from an autopsy specimen of human brain of a diagnosed case harboring numerous NCC. We randomly sampled 40 closely located cysts. Gross morphology of the cysts was studied on 2–3-micron hematoxylin-eosin stained sections, using low magnification of ×4. Higher magnification was used to study microscopic details in areas of interest. Thirty cysts with identifiable features were included in the analysis. The morphological details of the scolex like number, position, integrity, and degenerative changes were noted. Features of the cyst wall (contour, fragmentation, accessory cysts, and their contents) were also evaluated. Adjacent merging cysts were carefully observed for intercommunications.

Results

MR Imaging

Of the 23 conglomerated cysts, 11 were paired, six had three and four had four cysts. Two cysts were single with undulations of wall. Multiple overlapping features of degeneration were noted in the parasites. In three cases, preserved scolex was seen as an invaginated curled structure in the cyst with its stem attached to the cyst wall. On 3D high resolution images, three to four knob like suckers were seen in the head, showing intermediate T1 and T2 signal. (Figures 1(a) and (b)) In two cases suckers showed high T2 signal due to hydropic degeneration. (Figure 1(e)) 20 cysts were communicating (87%); 13 with a wide communication and eight showed a narrow neck, subtle budding from wall or elongation of contour towards their companion. (Figures 2–4) No communication could be demonstrated in two cysts. Three lesions had a pseudo-tumoral multi-cystic pattern. (Figure 5 and 6)

Figure 1.

Anatomy of intact cysticercus. (a)–(c). T1 MPRAGE (a) and 3D CISS volume extracted representation (b) show head and neck of invaginated scolex. The head bears four suckers. (c). Histopathological cross-section. Suckers (long arrow), rostellum with hooklets (curved arrow), alimentary canal (asterisks), inner chamber around the scolex (short arrow) and thin capsule of outer chamber of the cyst (arrow head) are marked. Early degeneration of scolex (d) seen as calcification (long arrow) and hydropic changes (short arrow). (e). T2 CISS image shows hydropic and calcific degenerations appearing bright and dark respectively. (f). Early degeneration of the cyst wall on histopathology. Subtle budding cyst in the pliable wall of cyst retracted from the parenchyma (curved arrow) inciting perilesional acute edema (black asterisk). The parent cyst wall is adherent to gliotic changes in the brain parenchyma. (white asterisk).

Figure 2.

Early degeneration of cyst wall in two cases. ((a)–(c)). Same case as Figure 1(a). (a). Post contrast T1 WI. Shows scolex containing cyst in the right parietal lobe and subtle budding daughter cyst with inflammatory enhancement (arrow). (b). One year follow up CT scan shows involution into a calcific focus (arrow). Second case ((c), and (d)). T2 FLAIR (c) and 3D CISS volume extracted image (e) shows budding daughter cysts (arrowheads). The curled scolex with head and suckers is seen within the cyst (arrow d). A later stage. E-H. Axial T2 TSE (a) and SWI image (b) shows dual communicating cysts. The lateral cortical cyst with thicker and darker wall is the parent cyst (short arrows (e)). The signal drop on SWI image (f) is due to scolex at the junctional area. The medially directed daughter cyst has poorly defined wall and more inflammatory edema (long arrow E). (g). Post contrast T1 MPRAGE shows the communicating RELs. (h). On DWI (upper) and ADC (lower) images both show restriction of diffusion, more so the daughter cyst.

Figure 4.

Similar findings as Figure 3. in different cases ((a)–(d)) & ((e), and (f)). Coronal CT scan shows scolex within the vesicle B. Coronal T2 FSE image shows thicker and darker wall of the parent cyst (upper arrow) and ill-defined daughter cysts with edema (lower arrow). (c). Post contrast T1 MPRAGE shows RELs with communication of daughter cysts and diffusion restriction (arrow (d)). E, F. Lateral parent cyst (arrow e) and acutely inflamed medial accessory cysts showing contrast smudging of surrounding brain due to BBB leakage (arrow (f)). Evagination of scolex on histopathology (white arrow (g)) and its MR equivalent on contrast T1 WI (h). The scolex is uncovered due to separation of membranes inciting acute parenchymal edema (black arrow (g), and enhancement (h).

Figure 5.

Resolution of two multi-cystic pseudo-tumoral lesions.((a)–(d) and (E)–(H)). (a). T2 FSE axial section in a 55-year female being followed up for enlarging lesion. She was considered for starting ATT but managed on anti-convulsants only. (b). T1 contrast sagittal. 5months later the lesion shrunk into a small REL (arrow). (c). CT scan after 2 years shows a calcific residue without edema. CT after recurrent seizures at 7 years shows reappearance of edema (arrow). Patient is on long term anti-convulsants. (e), and (h). 35-year male on cysticidal treatment. E, F. T2 TSE and T1 contrast axial images reveal a complex pseudo-tumorous lesion (arrow). (g). Axial CT contrast image shows marked shrinkage in size after 1 year (arrow). (h). The lesion finally resolved after 3 years into a gliotic focus and faint calcification (arrow).

Figure 6.

Pseudo-tumorous NCC in a 35-year female. (a) T2 TSE coronal image shows a focal lesion with edema in right parietal lobe with visible scolex (arrow). (b), and (c). After 5 months, coronal T2 and T! contrast axial image show a conglomerated enhancing lesion with a laterally enlarging accessory cyst. (d) Perfusion imaging shows hypoperfusion ruling out a tumor. (e) On SWI the scolex is still visible embedded within the wall of the parent cyst. (f) T2 TSE coronal image on follow up at 7 months shows reduction in size and edema.

The scolex containing cyst with thicker T2 hypointense wall was labeled as parent cyst in 16 cases. These were superficially located in 13 cases (cortical or juxtacortical). Rest of the cysts, labeled as daughter cysts, were directed away towards the white matter. Daughter cysts had poorly defined thinner walls, cyst to cyst variation of T1/T2 signal, and florid edema in adjacent white matter (n = 19). (Figures 2–4) On contrast enhanced images, they had poorly defined walls and subtle or frank perilesional enhancement. Diffusion images, available in 13 cases, showed restricted diffusion in 51% (18 of 35 cysts), more commonly in daughter cysts (n = 12) compared to parent cysts (n = 6). (Figures 2–4) Scolex was identified as T2 dark structure in 20 lesion complexes and, was solitary in all. It also appeared dark on SWI in 15 patients. The scolex was either located within the parent cyst (n = 9) or was labeled junctional when incorporated into the interface of cysts (n = 11). (Figures 2, 3, and 6) Available CT scans confirmed scolex in seven patients as a hyperdense nodule (four on initial scan and three on follow up). (Figures 2 and 4) On serial imaging, two of three multi-cystic pseudo-tumoral lesions, resolved into solitary fibrocalcific lesions over 2–3 years with clearance of edema. (Figure 5) Both needed long term anti-epileptics. In one patient, recurrent seizure caused re-emergence of edema around the calcified focus after 7 years. The third lesion serially enlarged over 5 months in spite of ATT, but started resolving after 7 months. (Figure 6)

Figure 3.

Conglomeration of multiple pleomorphic cysts. (a), and (b). T2 TSE axial and sagittal sections show a complex of four cysts. The parent cyst is cortical (long arrow (a)). The daughter cysts in different stages are posteromedial with immature walls and perilesional white matter edema (arrow heads). (c). On T1 post contrast sagittal image, cysts show communications and ring enhancement.(arrow). (d). On FLAIR axial image the secondary cysts are not suppressed (arrow head) due to inflammatory turbidity compared to anterior cysts (arrow) and show diffusion restriction on DWI image (e). (f). SWI phase image shows signal drop in the scolex (arrow).

Histopathology

Out of 30 lesions studied, 14 were dual cysts, eight had frank undulations of walls and rest eight were partially crumpled lesions. Nine dual cysts were communicating. In rest, communications could not be made out (possible non-inclusion into the sections). Internal structure in preserved scolices was well demonstrated in 12, with up to four oval suckers, rostellum with hooklets and a convoluted alimentary canal. (Figure 1(c))

In all lesions, the scolex or its remnant was solitary, located either in the parent cyst or in the junctional area of cysts. The scolex and the cyst wall showed a combination of degenerative features. Early degeneration of the scolex was seen as calcification and hydropic changes (Figure 1(d)) and advanced degeneration as a fragmented remnant. (Figure 7) The scolex was uncovered through disruption of its investing layer (labeled evagination) in seven parasites. (Figure 4(g) and (h)) The wall changes were subtle undulations (n = 8), (Figure 1(f)) widely communicating loculi (9 of 14 dual cysts) or, crumpled cysts with variable fibrocalcific-granulomatous changes (n = 8). (Figure 7) Organized fibrosis was seen around parent cyst or the junctional area in a number of lesions. The cyst wall was adherent to this zone of fibrosis. Accessory cysts had thinner capsule which had peeled off from parenchyma on post mortem specimen and were surrounded by acute inflammatory edema. (Figures1(f) and 7) The variable acute and chronic perilesional inflammation comprised of lymphoplasmacytic infiltrates, eosinophils and multinucleated foreign body giant cells. Fibrillary astrocytosis and spongy changes were noted in peripheral neural tissue. (Figure 7) Following histo-morphological patterns were suggested as representatives for comparison with imaging. To eliminate bias towards isolated findings, the pattern was selected only if seen in at least five different specimen.

• 1. Most closely placed cysts communicated with each other.

• 2. In complex lesions, maximum organized inflammation and adherent fibrosis was around the parent cyst or at the junctional zone of the cysts.

• 3. The scolex was solitary and located in the parent cyst or at the junctional zone of the cysts in all cases.

• 4. Daughter cysts did not contain scolex, had a retractable thinner wall and greater perilesional acute inflammation.

• 5. Uncovering of scolex (evagination) was a recognizable feature.

Figure 7.

Histopathology of advanced degeneration. The disintegrated remnant of scolex head (black arrow) still attached to the basal fibrotic wall of cyst (black arrowhead). Rest of the cyst wall show multiple non adherent undulations and accessory loculi. (b) and (c). The basal disintegrating remnants of scolex (arrows). (d)–(f). Typical inflammatory reaction around the parasite in advanced degeneration. (d) Dense fibrosis/gliosis seen around parent cyst which is most prominent at the junctional zone (black arrowheads). A thick septum is noted between the neighboring cysts (arrow). Acute inflammation is seen on the opposite side (white asterisk). Intra-cystic structure is an artifact (black asterisk). (e) (magnified inset of A). Perivascular lymphocytic infiltration (asterisk), fibrillary astrocytosis of neurons with spongy change (arrow) and, foreign body type multinucleated giant cells are visible (curved arrow). (f) Perilesional eosinophilic infiltration around the parasite is indicated by the curved arrow.

Discussion

In developing world, NCC is the commonest neuro-parasitic disease and accounts for acquired epilepsy in 80% of all cases.¹Two third of the lesions present as solitary SCG in younger adults, a benign form with muted immune response against the parasite.^2,5,16 Because of low sero-positivity of immunological test in these patients, the diagnosis of NCC is often presumptive based on consensus guidelines.^17–19 If solitary REL has a size exceeding 2 cm, thick irregular wall, conglomeration of RELs, excessive edema/mass effect, and no visible scolex, a diagnosis other than NCC should be considered. Raised intracranial pressure, neuro-deficits, and non-response to cysticidal drugs, also suggest an alternate diagnosis.^6,11,19 Demonstration of eccentric mural nodule in a thin-walled clear cyst smaller than 2 cm, is diagnostic of vesicular NCC. It is a viable, non-inflamed, and clinically benign form of the parasite with CSF like imaging character. The next stage is colloid vesicular, which often presents with seizures. In this stage, cyst wall breach leads to exposure of cyst content and antigen triggered inflammation (edema) and contrast enhancement. The cyst wall becomes irregular, contents turn progressively turbid, and hyaline degeneration of the scolex occurs. This results in increased density on CT and higher T1 signal intensity on MRI. Over a variable time, the parasite involutes into a granulo-nodular lesion (further shrinkage in size, thickening of wall, and reduction in edema). The final stage is of a fibrocalcific remnant, a round calcified nodule best shown on CT scan, generally with resolution of edema and enhancement .^7–9,20

At times, the dying parasite presents as a conglomerated or “multi cystic tumorous” morphology, either coinciding with initial seizure or on follow up. It may also show a paradoxical increase in size after initiation of treatment. In such lesions, other possibilities like tuberculosis, tumors, fungal lesions, toxoplasma, and demyelination need to be ruled out.^11–16 We have frequently encountered such ambiguous lesions, which resolved spontaneously or after cysticidal treatment. Previously considered unusual, Garg et al. recently highlighted such phenotype in more than half of their cases on CT scans.^10–12,15 Epidemiologically, tuberculosis is also prevalent in NCC endemic populations. Tuberculomas also present similarly on imaging with only a minority of cases having other supporting features outside CNS. Untreated, tuberculosis progresses and has worse outcome. Conversely, anti-tubercular drugs are potentially toxic and poorly tolerated. ⁶ Many complex cysticercus lesions are wrongly treated for tuberculosis, sometimes for long durations. Thus, it is imperative to distinguish the two, a fact also emphasized in the consensus guidelines.^17,18 On the other hand, in non-endemic areas, such cysticercus lesions may mimic primary and metastatic tumor resulting in surgical interventions as shown in a recent review of literature. ¹²

The time-honored imaging stages of NCC do not take into account or explain such lesions. In spite of stated difficulty in obtaining parasites in early stages for histopathology, morphology of viable larva and its early degenerative changes are well described. ²⁰ However, there is scanty description of corresponding radiological equivalents, understandably because follow up imaging is too far spaced and lesion resection is seldom performed. We believe that passage of parasite between vesicular and colloidal stages can be dramatic with a number of events. It cannot be generalized as a ”two stage phenomena” and needs expansion. Advances in imaging technology have revolutionized the diagnosis and management of NCC.^8,21–25 SWI, DWI, and 3D high resolution fluid sensitive imaging are routinely used to better define scolex and cysts. ⁹ However, for early transitions, a corresponding improved insight is not reflected in the imaging literature. ²² In this study, we have tried to expand the radiological perspective using correlative radio-histopathology patterns with a focus on interpretation of conglomerated complex lesions.

Understanding some initial events is important. The scolex is the key for proliferation of parasite. After accidentally finding its way into human brain, the metacestode lodges in the terminal capillaries, and thus, has reached a dead end of life cycle. The protoscolex invaginates into an immune protective vesicle and is incapable of reproduction. ²⁶ On high resolution MRI, the finer details of parasite need elaboration. The description of scolex as eccentric ”dot within hole” is an oversimplified term. High resolution imaging of relatively preserved parasites in our cases, showed protoscolex as an invaginated curled structure attached to the smooth cyst wall by its neck. The head revealed 3–4 nubbins, representing suckers. On volume extracted images, it looked remarkably similar to the head of intestinal Taenia. (Figures 1(a) and (b)) Corresponding histological pattern also well depicted the structures of the parasite, that is, scolex with suckers, hooklets bearing terminal rostellum, the spiral alimentary canal, and the cyst wall. (Figure 1(c))

After an uncertain initiating event, possibly enhanced immune attack, self-programmed death or, cysticidal treatment, the parasite undergoes degeneration and induces immune mediated inflammation.^26-28 Simultaneously, there is an abortive attempt of reproduction, with formation of non-larval daughter cysts and membranes. Intraventricular cysticercus larvae have been reported to repeatedly evaginate and invaginate in search of appropriate location for attachment. ²⁹ Possibility of an attempted evagination of scolex in parenchymal cysts as a preterminal event cannot be ruled out.

In some cases, histology demonstrated calcification and hydropic degeneration in the head of the scolex corresponding to early degeneration. On MRI, some suckers showed T2 hyper intense core, possibly also representing hydropic degeneration. (Figure 1(e)) In early degeneration, the wall of the parent cyst becomes undulating or forms small outpouchings. (Figure 1(f) and 2) Later frank daughter cysts form, seen as clusters of two or more cysts arranged around the parent cyst. (Figures 2–4) In such lesions, parent larval cyst presumably established in the brain for a longer time, is identifiable by a prominent T2 hypointense wall due to chronic inflammation. The scolex is either within it or trapped at the junctional region of the cyst interface. Thus, the scolex was solitary in all cases, and appeared as a T2 hypointense focus with variable susceptibility on SWI and calcific density on CT scan. (Figures 2–6) Corresponding histo-morphological pattern was a cyst with perilesional organized adherent chronic inflammation or fibrosis with a solitary preserved or variably degenerated scolex. The hydropic daughter cysts were without scolex, indicating their asexual non-larval nature. Being recent in origin, they had immature pliable walls which on post mortem specimen clearly retracted from surrounding tissue. (Figure 1(f) and 7(a)) They were surrounded by acute inflammatory reaction and possibly disruption of BBB, leading to perilesional contrast smudging by extravascular leakage of contrast on MRI. (Figure 4(c) and (f)) Restricted diffusion on MRI was common and more often associated with inflamed daughter cysts. Proteinaceous turbidity of the cyst fluid explains diffusion restriction and varying T1/T2 signal from cyst to cyst. (Figures 2, 3, and 4) Such imaging pleomorphism is a confounder to be kept in mind. As suggested on histology correlates, the scolex subsequently disintegrates and disperses as calcareous debris in the granuloma. The attachment of the scolex at the cyst wall often corresponds to maximum fibrosis and is the last to disappear or may persist as an eccentric calcified remnant. (Figure 7(a)–(c)) Eventually, the parasite shrinks into a fibrocalcific focus as seen on imaging in three patients on follow up of 2–3 years (Figure 2 and 5)

Interestingly, the three pseudo-tumorous lesions had a bizarre evolution into multi-cystic edematous complexes. All had a solitary identifiable scolex and developed serially enlarging communicating accessory loculi. Two lesions resolved into a single calcific granuloma over 2–3 years, highlighting evolution from a single parasite. Both patients needed long term antiepileptic treatment. One patient had recurrent seizures with reappearance of edema after 7 years (Figure 5(c) and (d))

The third lesion, serially enlarged in spite of ATT and finally started involuting after 7 months and is prototype of the diagnostic dilemma faced. (Figure 6) The other surprise on histology was demonstration of frank or forme fruste of evagination of scolex in multiple cases. A radiological equivalent was difficult to find possibly due to lower imaging resolution or transient nature of evagination which may be rapidly encircled by proliferating membranes. (Figure 4(G) and (H))

The appearance of multiple cysts is a sequential degenerative phenomenon after death of the parasite is initiated. Thus, we believe that, in complex multi-cystic lesions, the presumed established parent cyst is the larval cyst, surrounded by chronic inflammation and gliosis. Remaining cysts are asexual non-larval daughter cysts arising from a common parent cyst and are not separate parasites They invoke acute neurological symptoms due to brain inflammation induced by intense immune response launched against exposed cyst contents. Histological markers of perilesional acute inflammation were infiltration of eosinophils, lympho-plasmacytes and multinucleated foreign body giant cells and only milder gliotic reaction. Fibrillary astrocytosis of surrounding neurons with spongy cavitation indicate encephalitic damage. Contrarily, established parent cysts had dense irregular gliosis, mostly around basal part of the scolex or at the junctional region of cysts, surrounded by variable lymphoplasmacytic infiltrates, multinucleated cells and eosinophils. (Figure 7 (D), (E) and (F))

Though cellulose is the dominant parenchymal form in our setting, it shares common histology with racemose form (which is a distinct imaging entity of extra-parenchymal form of cysticercus, consisting of multiple clear cysts/membranes and no a demonstrable scolex). Both are considered larval stages of T solium and co-exist in brain in 10% cases.^30,31 It is also argued that all apparent parenchymal cysts are sub-arachnoidal in location and admittedly the racemose form may arise from segmentation of cellulose form.^20,30–32 Aggregated cysts containing degenerated scolex remnants and sprouting and enlarging loculi suggests that during degeneration C cellulose undergoes a “limited racemose like transition,” only that its growth is restricted by inflamed parenchyma. Similar descriptions have been reported previously.^2,20,30–33 Thus, parenchymal cyst can take either form, assume an overlapping intermediate morphology or even co-exist in the same patient as hinted by Rabiela et al.^30,31 Since Racemose or transitional forms are exclusively found in humans, it may reflect a unique host parasite interaction. ²⁰

Our findings may have important clinical implications. We hypothesize that such complex lesions may present with disproportionate neurological signs and deficits. Moreover, on follow up, recurrent seizures can be caused by calcified SCG due to episodic antigenic challenge.^34–37 Previous studies have also shown that perilesional gliosis is the most common pathological finding in SCG and is a seizure substrate.^8,38 The complex cysticercus lesions, may take longer to involute and may induce more epileptogenic scarring/dystrophic calcification. The treatment may be accordingly adjusted including anti-inflammatory measures for acute management and to minimize sequel of inordinate immune reaction. Further, such morphology may not warrant a change of diagnosis or treatment, particularly switching over to anti-tubercular drugs or aggressive neurosurgical intervention. Finally, anti-epileptics should not be prematurely tapered and the patients may need long term treatment and follow up. There are limitations of this study. The diagnosis of NCC was based on consensus guidelines which is nonetheless justified in our setting. From immunological perspective, the histological samples from unrelated post mortem brain, may not be exact morphological representatives of imaged lesions. However, the brain specimen did show a spectrum of degenerated lesions with significant acute and chronic inflammatory reactions which may be a surrogate indicators of the parasite’s biological course in human brain. Finally, some of the conclusions of our study are logical derivatives and hypothetical in nature. They need validation on further studies, so as to fill the knowledge gaps in our understanding of this important public health issue.

To conclude, early degenerative transitions in brain parenchymal cysticercosis are eventful and need to be understood to correctly differentiate complex conglomerated cysticercus lesions from other differentials. High resolution MR sequences can be helpful in this. We hypothesize that, the most prevalent parenchymal form of NCC, C cellulose larva may sometimes undergo a “limited racemose like transition” before complete degeneration. Thus, conglomerated cysts arise from a single larva and by enhanced antigen exposure, responsible for severe flaring up of immune reaction. Such lesions may cause more scarring and calcification, thus may be potentially more epileptogenic and need an adjusted therapeutic approach.

Appendix

Abbreviations

ATT

Anti-tubercular treatment

CISS

Constructive interference in steady state

NCC

Neurocysticercosis

REL

Ring enhancing lesion

SCG

Single cysticercus granuloma

SPACE

Spatial acquisition with contrast enhancement

ORCID iDs

Chirag Kamal Ahuja https://orcid.org/0000-0003-0734-3252

Sameer Vyas https://orcid.org/0000-0002-0113-0486

Manoj Goyal https://orcid.org/0000-0001-7375-4215