Magnetic resonance imaging features of pathologically proven cerebral sparganosis

Abstract

Objective

The purpose of this study was to identify characteristic magnetic resonance imaging (MRI) features of cerebral sparganosis, a rare parasitic disease caused by the plerocercoid larva of Spirometra mansoni.

Methods

This retrospective study reviewed medical records, computed tomography (CT) and MRI scans and pathological specimens from patients with pathologically proven cerebral sparganosis. The location, signal intensity and contrast enhancement characteristics of the lesions were assessed.

Results

Records of 12 patients (seven male and five female; age range 8–35 years) were reviewed. A total of 13 lesions were identified: of the 10 patients with supratentorial lesions, nine had a single lesion and one had bilateral hemispheric lesions. Two patients had a single lesion in the ependyma of the 4^th ventricle. All lesions were iso-hypointense on T1-weighted images, slightly hypointense on T2-weighted images and surrounded by extensive oedema. Ten of the 13 lesions demonstrated a ‘string-knots sign’, characterized by a tangled string in a knot-like shape on contrast-enhanced MRI.

Conclusion

A string-knots sign enhancement pattern in cortical–subcortical regions should suggest the diagnosis of cerebral sparganosis.

Introduction

Cerebral sparganosis is a rare parasitic infection that produces longstanding inflammation of tissue within the brain; it is caused by infestation by the larval cestode of the genus Spirometra, including the plerocercoid larva of Spirometra mansoni.^1,2 Although a definite diagnosis is made when the larval worm is surgically removed, a diagnosis can also be suspected based on the combination of radiological features and a positive antibody test for sparganum larvae. This diagnostic method is particularly useful in young patients living in areas where the infection is endemic (such as East Asia), although some cases have also been reported in North America and Europe.^3–6 The prevalence of cerebral sparganosis is likely to be underestimated as a consequence of the fact that many cases in developing countries probably go unreported. For example, only a few published papers (most of which report single or just a few cases) were identified via a search of the PubMed® database,^7–9 while around 100 cases of de novo cerebral sparganosis are likely to be diagnosed within Shanghai, each year. In the public health system, progressive implementation of cross-sectional imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) helps to explain the increased prevalence of cerebral sparganosis in China.^10,11 As a consequence of these technological advances, it has become necessary for physicians to familiarize themselves with the CT and MRI features of cerebral sparganosis, in order to suggest it as a possible diagnosis in patients who usually present with nonspecific clinical findings.

The purposes of this study were to analyse retrospectively the CT and MRI imaging features of patients with cerebral sparganosis and to identify characteristics that could help in supporting this diagnosis.

Patients and methods

Patients

Consecutive patients with cerebral sparganosis who underwent surgery at the Department of Radiology, Huashan Hospital, Shanghai, China between January 1999 and December 2010, were enrolled in this retrospective study. Their medical records, imaging findings and pathological specimens were retrospectively reviewed. A diagnosis of cerebral sparganosis was based on the demonstration of an intact/dead worm (sparganum larva) during surgical resection. The study protocol was approved by the Institutional Review Board of Huashan Hospital. There were no exclusion criteria. All patients participating in the study provided verbal informed consent.

CT and MRI scans

The MRI examinations were performed with patients in the supine position, using a 3.0 T MRI system (MAGNETOM® Verio; Siemens, Erlangen, Germany) with a 32-channel head coil. Images were obtained in the axial plane parallel to the bicommissural line. Post-contrast images were acquired after an intravenous injection of 15 ml gadopentetate dimeglumine (Beijing Beilu Pharmaceutical Company, Beijing, China). MRI scans were evaluated by two experienced radiologists (S. C. and G. G.) blinded to the clinical information. Pre-contrast CT scans were performed on a Siemens system with four detectors (SOMATOM® Emotion; Siemens). A complete medical history was taken from each patient and all neurological symptoms prior to the MRI or CT brain scans were recorded. All patients underwent open brain surgery with removal of the lesions, following standard procedures.

Blood, CSF and histological analyses

Results of routine blood and cerebrospinal fluid (CSF) analyses were retrieved from the medical records of each patient. The results of routine histological analyses of brain lesions were retrieved from the medical records of each patient.

Results

This study retrospectively examined the medical records, imaging and blood, CSF and histological findings from 12 consecutive patients (seven male, five female) aged 8–35 years (mean age 19 years) with cerebral sparganosis, who underwent open brain surgery to remove sparganum larvae. Unenhanced and contrast-enhanced MRI scans were obtained in all 12 patients; unenhanced brain CT scans were obtained in eight patients. Nine patients came from rural areas and none of the patients had a previous history of fever. Two patients had a history of eating raw or undercooked intermediate hosts of S. mansoni (such as frog or snake). The possible origin of one patient’s infestation was unavailable. A summary of the demographic and clinical characteristics of the 12 patients is presented in Table 1.

Table 1.

Demographic and clinical characteristics of 12 patients with cerebral sparganosis who underwent open brain surgery for lesion removal.

Patient no.	Age, years	Sex	History	Major clinical findings	Time since symptom onset	Blood/CSF antibodies to Spirometra mansoni a	Diagnostic evidence
1	17	Female	Rural area	Limitation of eye movement/facial paresis/diplopia	50 days	NA	Intact moving worm, ∼9.5 cm long, at surgery
2	35	Male	Frog legs ingestion	Numbness of right lower limb/focal epileptic seizures	12 months	Blood (−)	Worm remnants, ∼2 cm long, at surgery
3	15	Male	Rural area	Recurrent epileptic seizures/numbness of right lower limb	12 months	NA	Worm remnants at surgery
4	32	Female	Snake ingestion	Focal epileptic seizures	1 day	NA	Worm remnants at surgery
5	11	Male	NA	Focal epileptic seizures	6 months	NA	Worm remnants at surgery
6	13	Male	Rural area	Dizziness/headache/vomiting	2 weeks	CSF (+)	Worm remnants at surgery
7	13	Male	Rural area	Focal epileptic seizures	2 months	NA	Intact moving worm, ∼8 cm long, at surgery
8	15	Male	Rural area	Focal epileptic seizures	4 days	NA	Worm remnants, ∼1 cm long, at surgery
9	24	Female	Rural area	Numbness of right upper limb	4 months	Blood (+)	Worm remnants at surgery
10	20	Female	Rural area	Numbness of left upper limb	10 months	Blood (+)	Intact moving worm at surgery
11	29	Male	Rural area	Headache/vomiting	4 months	NA	Worm remnants at surgery
12	8	Female	Rural area	Recurrent focal epileptic seizures	24 months	NA	Two intact moving worms at surgery

a

Findings of routine blood and cerebrospinal fluid (CSF) analyses were retrieved from medical records. Serum enzyme-linked immunosorbent assays for antibodies to Spirometra mansoni in serum and CSF were performed in a limited number of patients, because presurgical diagnosis did not anticipate a parasitic infection. NA, not analysed.

In total, there were 13 lesions. A summary of the radiological features presented in each patient is shown in Table 2. Of the 10 patients who demonstrated supratentorial lesions (patients 2–11), six (patients 2, 3, 4, 5, 7 and 8) presented with new-onset focal epileptic seizures, four of them in isolation (patients 4, 5, 7 and 8); two patients (patients 2 and 3) had epileptic seizures associated with focal neurological deficits, such as motor weakness and lower-limb numbness. Two patients (patients 9 and 10) presented with limb numbness in isolation. One patient (patient 6) presented with nonspecific dizziness/headache/vomiting and a second patient (patient 11) presented with nonspecific headache/vomiting; both sets of symptoms suggesting increased intracranial pressure. The remaining two patients had lesions associated with the ependyma of the 4^th ventricle, one (patient 1) presented with limitation of eye movements, diplopia and facial paresis; the other (patient 12) presented with recurrent focal epileptic seizures. Neurological symptoms had manifested between 1 day and 24 months before brain CT or MRI scans were performed.

Table 2.

Radiological features evident on magnetic resonance imaging (MRI) and computed tomography (CT) scans from 12 patients with cerebral sparganosis.

Patient no.	Lesion location	Major MRI finding	Atrophy/enlarged ventricle	Calcification on CT
1	Ependyma of the 4th ventricle	String-knots sign	Yes	NA
2	Left parietal lobe	String-knots sign	No	Yes
3	Right frontal lobe	String-knots sign	No	NA
4	Right frontal lobe	String-knots sign	No	No
5	Left frontal lobe	String-knots sign	No	NA
6	Left deep white matter	String-knots sign	No	No
7	Right frontal lobe	String-knots sign	No	Yes
8	Left frontal lobe	String-knots sign	No	Yes
9	Left frontal lobe	Tunnel sign	Yes	No
10	Right thalamus	Nodular shape	Yes	Yes
11	Left frontal lobe and  right parietal lobe	String-knots sign  in both lesions	No	NA
12	Ependyma of the 4th ventricle	Nodular shape	No	No

NA, not available.

All 12 patients underwent open brain surgery with removal of the sparganum larval worms. In four patients (patients 1, 7, 10 and 12), five moving intact S. mansoni worms were found at surgery, with the longest worm being 9.5 cm. In the remaining eight patients, haematoxylin and eosin staining of the pathological specimens showed remnants of dead worms. Serum enzyme-linked immunosorbent assay (ELISA) for S. mansoni was performed in only three patients; results were positive in two (patients 9 and 10). ELISA of the CSF was positive for S. mansoni in one patient. In the remaining eight patients, no serum or CSF tests for S. mansoni were performed, as the presurgical diagnoses did not anticipate parasitic infections.

Magnetic resonance imaging showed a total of 13 focal contrast-enhancing brain lesions in the 12 patients (Table 2). Nine of the 13 lesions had a superficial location involving the cortico–juxtacortical junction: three in the right frontal lobe (patients 3, 4 and 7); four in the left frontal lobe (patients 5, 8, 9 and 11); one in the left parietal lobe (patient 2); one in the right parietal lobe (patient 11). Two lesions were located deeply: one in the right thalamus (patient 10) and one in the left periventricle white matter (patient 6). Two patients’ lesions were in the ependyma of the 4^th ventricle (patients 12 and 1; one in the bottom and the other in the right side, respectively).

All of the lesions were ill defined, with mixed signal intensity on T2-weighted MRI scans, and were surrounded with variable degrees of vasogenic oedema producing a mild or moderate mass effect. On contrast-enhanced T1-weighted MRI scans, the lesions were better defined when measuring 20–30 mm in maximum diameter. A contrast-enhancing pattern, which looked like a tangled string in a knot-like shape (defined as the ‘string-knots sign’), was present in 10 lesions (Figures 1–4). A tunnel sign, defined as a hollow tube with peripheral contrast enhancement, was identified in one case (patient 9). Two cases demonstrated a nonspecific nodular enhancement pattern (patients 10 and 12). One patient (patient 1), who had a lesion in the right ependyma of the 4^th ventricle, showed a substantial enlargement of the whole ventricular system. Two cases (patients 9 and 10) presented with focal cortical atrophy or ipsilateral ventricular dilatation, which are indicative of secondary degenerative changes.

Figure 1.

A13-year-old male (patient 7) with a 2-month history of epileptic seizures was shown to have a lesion located in the right frontal lobe. An axial computed tomography scan showed slight calcification (arrow) (A). An axial magnetic resonance imaging scan revealed a superficial lesion with central slight hypointensity on a T2-weighted image surrounded by hyperintense oedema (B). The enhancement was considerable and showed a ‘string-knots sign’ in the sagittal plane (arrow) on a T2-weighted image (C). An intact, live, pale-coloured worm ∼8 cm long (demonstrating peristalsis) was found at craniotomy (D).

Figure 2.

A 17-year-old female (patient 1) with a 50-day history of limited eye movement and a 3-day history of right distortions of the lip commissure was shown to have a lesion in the ependyma of the 4^th ventricle. Magnetic resonance imaging showed a mixed signal on a T1-weighted image in the sagittal plane (arrow) (A) and central slight hypointensity on a T2-weighted image, surrounded by hyperintense oedema in the axial plane (arrow) (B). The enhancement was considerable, showing a ‘string-knots sign’ in the sagittal plane (arrow) (C) and many small circles in the axial plane (arrow) on T2-weighted images (D). An intact live worm ∼9.5 cm long, demonstrating peristalsis, was found at craniotomy.

Figure 3.

An 11-year-old male (patient 5) with a 6-month history of epileptic seizures was shown to have a lesion situated superficially on the left frontal lobe. Axial magnetic resonance imaging showed a mixed iso-hypointense signal on a T1-weighted image (arrow) (A) and central iso-hyperintensity on a T2-weighted image surrounded by hyperintense oedema (B). The enhancement was considerable and showed a ‘string-knots sign’ in the sagittal (arrow) (C) and axial (arrow) (D) planes on post-enhanced T1-weighted images.

Figure 4.

A 35-year-old male (patient 2) with a history of right lower limb numbness for 1 year and sudden onset of epileptic seizures 15 days before being scanned was shown to have a lesion situated superficially on the left parietal lobe. An axial computed tomography scan showed slight calcification (arrow) (A). Axial magnetic resonance imaging showed mixed central iso-hyperintensity on a T2-weighted image surrounded by hyperintense oedema (B). The enhancement was considerable and showed a ‘string-knots sign’ in the axial (arrow) (C) and sagittal (arrow) (D) planes on post-enhanced T1-weighted images.

Unenhanced CT scans (performed in eight patients) showed low-density lesions involving the juxtacortical brain hemispheric white matter, mainly representing vasogenic oedema, with a mild or moderate mass effect. Of these eight patients, small punctuate calcifications were found in four cases (patients 2, 7, 8 and 10).

Discussion

This retrospective analysis of a series of 12 pathologically proven cases of cerebral sparganosis due to S. mansoni larvae demonstrated that a novel string-knots sign in the cortico–subcortical region was a characteristic radiological feature, which has not been previously described. The presence of this string-knots sign – particularly in young patients living in regions that are endemic for this parasitic infection (such as China, Southeast Asia, Japan and Korea), where uncooked or partially cooked freshwater fish, frog or snake are eaten – should suggest a diagnosis of cerebral sparganosis. ¹²

The most common clinical manifestations of sparganosis in humans are slowly growing, migratory subcutaneous or muscle nodules, although these nodules may also involve the abdominal cavity, pleura, genitourinary tract, eyes and spinal cord.^12–18 Infestation of the central nervous system (CNS) is rare: a fact that can be explained by the long length of the cestode worm (which prevents it from directly entering the CNS via the bloodstream). However, the much smaller procercoid stage of larva may reach the CNS and grow to the plerocercoid stage.^12,18 Sparganum larva is characteristically a ribbon-shaped worm of varying length (ranging between 1 cm and 1 m). ¹⁹ Movement of a living sparganum larva inside the brain parenchyma can cause brain-tissue injury, leading to the formation of inflammatory granulomatous lesions that can explain the characteristic radiological appearance. Serial imaging demonstrated the development of a tunnel sign from an initial nodular lesion, with ring-like enhancement representing the moving track of a migrating worm. ² The characteristic features of sparganosis include a single brain focal ring-enhancing lesion with a tunnel-shape configuration, sometimes with a conglomerate pattern. ¹¹ This pattern could be explained by the viability of the cestode parasite with its migration through the brain parenchyma, ¹¹ which produces a long strip-like track of tissue injury and a corresponding tunnel-like enhancement pattern on MRI after the worm moves to another brain region. However, due to the random, slow rate of movement (wandering type) of the worm, typical tunnel-like lesions were uncommon on cross-sectional MRI in this current study.

In contrast, the most commonly observed enhancement pattern in this current series was the string-knots sign: nine of the 12 patients presented with a string-knots sign enhancement pattern, only one case presented with the tunnel sign, and two cases presented with nonspecific nodular enhancement. These current findings suggest that the string-knots sign is a more characteristic pattern for the diagnosis of sparganosis on contrast-enhancing MRI.

Some authors have suggested that the coexistence of old and new lesions is one of the radiological characteristics of cerebral sparganosis. ¹¹ In this current study of cerebral sparganosis, only two cases presented with some focal cortical atrophy or ipsilateral ventricular dilatation indicating secondary degenerative changes. The apparent discrepancy with this previous study can be explained by the fact that, in this current study, CT and MRI scans were obtained in most of the patients during the first months after symptom onset. This reflects the increasing availability of modern imaging techniques in patients living in areas endemic for this parasitic infection. ¹¹

In eight cases, CT scans were undertaken. Four of these eight cases presented with a single punctuate calcification inside the lesion. As these four cases had wide variations in time since symptoms onset (4 days to 12 months), these findings suggest that lesion calcification had no relationship with the duration of this parasitic infection, but there may be a relationship with the living status of the S. mansoni larva, as calcification never develops unless the worm has died.

Accurate diagnosis of this parasitic infection is essential in order to avoid the unnecessary use of therapies for mycobacterium infections, which are ineffective. Surgical excision of the granuloma is considered to be the treatment of choice, as it provides histopathological verification of the diagnosis, effectively controls seizures and prevents cognitive decline. ¹²

In conclusion, the string-knots sign enhancement pattern observed in the cortico–subcortical region is a characteristic imaging finding in the diagnosis of cerebral sparganosis, especially in young people living in areas endemic for sparganum infection. Surgical excision of the granuloma is considered to be the treatment of choice as it effectively controls seizures and prevents cognitive decline.