Diagnostic Challenges in Cerebral Schistosomiasis: A Case of Schistosoma japonicum Misinterpretation

Introduction

Schistosomiasis, a parasitic infectious disease caused by trematodes of the Schistosoma genus, poses a significant threat to human health [1]. According to 2019 data from the World Health Organization (WHO), approximately 236.6 million people globally are infected with schistosomiasis, resulting in an estimated 200 000 deaths annually and constituting a substantial global disease burden [2]. Schistosomiasis transmission occurs primarily through percutaneous exposure to freshwater contaminated with infective Schistosoma larvae. Cerebral schistosomiasis (CSM) occurs when Schistosoma eggs embolize through the bloodstream into intracranial regions, leading to ectopic deposition in the brain, cerebellum, brainstem, leptomeninges, and choroid plexus tissues, thereby inducing neuropathological changes. Schistosoma japonicum is a major cause of neuroschistosomiasis, with a reported prevalence ranging from 1.74% to 4.29% in endemic areas, though it remains clinically rare in non-endemic regions [3]. Notably, accelerated globalization has facilitated the spread of this traditionally geographically confined disease to new areas. For instance, a case report described a white man in Portugal diagnosed with CSM following seizures after returning from São Tomé and Príncipe [4]. There have been few systematic studies on the risk factors and clinical characteristics of CSM, and the condition is frequently misdiagnosed as other brain lesions. A definitive diagnosis often requires histopathological examination after craniotomy. Furthermore, studies indicate that approximately 90% of CSM cases are asymptomatic, with diagnosis often established post-mortem [5]. To reduce misdiagnosis rates and avoid unnecessary craniotomy risks in future similar cases, we report a case of chronic CSM with a clear epidemiological exposure history. Although this case was ultimately confirmed by surgical pathology, its diagnostic and treatment process suggests that integrating serological tests, molecular diagnostics, and multimodal imaging techniques can provide crucial diagnostic clues for high-risk patients. This provides a practical basis for establishing a clinical diagnostic framework and reducing reliance on neurosurgical intervention before obtaining definitive pathological evidence. This case study holds dual clinical significance: it elucidates the urgent need for a paradigm shift in diagnosing imported parasitic diseases in the context of global population mobility, and it demonstrates the critical role of comprehensively evaluating travel history, clinical manifestations, serological features, and imaging characteristics in optimizing clinical decision-making. These findings provide empirical evidence for establishing precise diagnostic pathways in non-endemic areas.

Case Report

A 28-year-old Chinese male office worker presented with an insidious onset of headache on March 3, 2022. The pain was described as a persistent, throbbing sensation localized to the parietal region, initially mild in intensity, for which he neither sought medical attention nor took any medication. By March 12, the headache intensified and shifted to the left temporal region, accompanied by a single episode of vomiting. During this period, he reported no fever, diplopia, visual impairment, tinnitus, hearing loss, speech difficulties, limb numbness/weakness, or gait instability. After 9 days of persistent symptoms, the patient sought care at Bao’an District People’s Hospital on March 17. A lumbar puncture revealed elevated cerebrospinal fluid (CSF) pressure. CSF analysis showed an increased white blood cell count of 50×106/L (adult normal reference range: 0–5×106/L), predominantly mononuclear cells (96%). Biochemical parameters indicated a chloride level of 119.0 mmol/L, with normal protein concentration. Brain MRI revealed abnormal signal intensity adjacent to the falx cerebri in the left parietal lobe (Figure 1). Following symptomatic treatment, including intracranial pressure reduction, the headache significantly improved, and he was discharged on March 28 with a diagnosis of “intracranial occupying lesion (suspected tumor)”.

On April 5, he was transferred to Shenzhen People’s Hospital for planned surgical treatment. A complete blood count showed: red blood cells 4.93×1012/L (adult normal range: 4.3–5.8×1012/L), hemoglobin 144 g/L (130–175 g/L), white blood cells 7.22×109/L (3.5–9.5×109/L), predominantly neutrophils (74.8%; normal: 40–75%), lymphocytes 15.2% (20–50%), monocytes 5.4% (3–10%), a slightly elevated eosinophil count of 4.3% (normal range: 0.4–4.0%), and basophils 0.3% (0–1%). The elevated eosinophil count raised suspicion for a potential parasitic infection. A brain computed tomography (CT) scan revealed a 31×28 mm space-occupying lesion in the left occipital lobe, with an extensive surrounding hypodense area. Significant compression and displacement of the left lateral ventricle were observed, with the posterior horn unclear and midline structures shifted to the right (Figure 2). Imaging findings suggested a left occipital lobe space-occupying lesion with significant perilesional edema.

On April 7, the patient underwent microsurgical excision of the left temporo-occipital lesion combined with duraplasty. The excised tissue was grayish-white to brownish, with a maximum diameter of 0.7 cm and a soft texture. Microscopic examination of the sections revealed numerous parasitic organisms accompanied by histiocytic infiltration, multinucleated giant cells, and neutrophils, with surrounding gliosis. These findings confirmed parasitic infection, but without definitive species identification. He was discharged on April 19 with a final diagnosis of “left parieto-occipital space-occupying lesion: parasitic infection”.

For definitive diagnosis and subsequent anthelminthic treatment, the patient was admitted to the National Clinical Research Center for Infectious Diseases at Shenzhen Third People’s Hospital on April 25, 2022, with an admission diagnosis of “cerebral parasitic disease”. The patient denied any history of chronic diseases such as coronary heart disease, hypertension, or diabetes, and no infectious diseases like hepatitis or tuberculosis. Physical examination revealed: temperature 36.2°C, pulse 92 beats/min, respiratory rate 20 breaths/min, and blood pressure 125/76 mmHg. Skin examination showed normal mucosal skin color, with no rash or subcutaneous hemorrhage. No superficial lymphadenopathy was palpable. Abdominal assessment revealed no tenderness or masses, and no hepatosplenomegaly was found upon subcostal palpation.

Hematological parameters showed: red blood cells 4.54×1012/L (normal: 4.3–5.8×1012/L), total white blood cells 10.19×109/L (3.5–9.5×109/L), neutrophils 67.91% (absolute count 6.92×109/L, normal: 1.8–6.3×109/L), lymphocytes 19.10% (20–50%), and eosinophils 0.60% (0.4–4.0%). A fecal occult blood test was positive, suggesting potential intestinal mucosal damage and the possibility of an intestinal S. japonicum infection. However, Kato-Katz thick smear microscopy, the WHO-recommended method for detecting intestinal schistosomiasis, revealed no parasitic eggs. Combined with the absence of peripheral eosinophilia, abdominal symptoms like pain or diarrhea, and normal abdominal ultrasound findings (no hepatosplenomegaly or intestinal wall thickening), the likelihood of active intestinal infection was significantly reduced. Considering the patient was in the postoperative recovery phase from neurosurgery, a colonoscopy was not performed. Abdominal ultrasound revealed renal calculi. To further clarify the diagnosis and rule out malignancy, Shenzhen People’s Hospital performed a repeat histopathological evaluation of the patient’s brain tissue. The results definitively showed Schistosoma eggs accompanied by granulomatous inflammation and small abscess formation, with no tumor cells identified. Combined with the eosinophilia observed earlier, these findings excluded a brain tumor, leading to a preliminary diagnosis of CSM.

On April 26, the patient’s venous blood sample was collected and sent to Guangzhou Da’an Clinical Laboratory Center for serological testing of antibodies against 9 human parasites. The results showed a positive ELISA for S. japonicum-specific immunoglobulin G (IgG) antibodies, while tests for Toxoplasma gondii, Paragonimus westermani, Clonorchis sinensis, Echinococcus granulosus, Cysticercus cellulosae, Diphyllobothrium mansoni, Trichinella spiralis, and Angiostrongylus cantonensis were all negative.

To confirm the previous diagnosis of “parasitic infection” at a more specialized infectious disease treatment institution and further identify the parasite species for targeted anthelmintic therapy, Shenzhen Third People’s Hospital re-examined the surgically excised brain tissue histopathologically on May 3, 2022. This review confirmed numerous S. japonicum eggs within the brain parenchyma (Figure 3), accompanied by granuloma formation and small abscess development. On May 10, the Shenzhen Center for Disease Control and Prevention in China re-examined the patient’s serum sample using ELISA, again confirming positive S. japonicum IgG antibodies. However, concurrent fecal modified Kato-Katz thick smear microscopy did not reveal any ova, suggesting a possible prior infection or low-level active infection. Integrating clinical manifestations, laboratory evidence, and epidemiological investigation, the preliminary diagnosis was established as imported chronic CSM, with Jingzhou City, Hubei Province, likely being the source of infection.

Antiparasitic treatment commenced upon hospitalization with praziquantel (0.6g per dose, 3 times daily; total cumulative dose: 7.2 g), alongside oral prednisone (5 mg per dose, once daily; total dose: 25 mg) for anti-inflammatory purposes and intravenous 20% mannitol (125 ml per dose, once daily; total volume: 500 ml) to reduce cerebral edema. After 12 days of targeted treatment, the patient achieved a clinically stable condition, with normal mental status, appetite, sleep patterns, and bowel/urinary function. He was discharged on May 7. During a 1-year follow-up assessment, the patient reported no clinical discomfort, and re-examination for S. japonicum IgG antibodies yielded negative results.

Epidemiological investigations showed that the patient studied at a university in Jingzhou City, Hubei Province, China (an endemic area for S. japonicum) between 2014 and 2018. From May to June 2017, he had contact with contaminated water in ditches and puddles with poor water quality and aquatic vegetation in the suburbs, providing a clear history of exposure to infected water and high epidemiological risk characteristics. According to data from the Centers for Disease Control and Prevention, Jingxi Village, the patient’s suspected exposure site, belongs to a S. japonicum endemic area, with a human seroprevalence of 3% in 2017, and Oncomelania snails were found in the ditch environment. The patient denied any other freshwater contact history in other schistosomiasis-endemic areas within China. Despite a clear exposure history, the exact time of infection could not be determined.

Discussion

This case report explores the diagnostic challenges of CSM and emphasizes the importance of recognizing its atypical manifestations for early identification and timely intervention. We present a case of CSM caused by S. japonicum, unique in its initial presentation of nonspecific headache, prolonged course, only mildly elevated eosinophil count (4.3%), and the absence of typical intestinal or hepatic symptoms commonly associated with S. japonicum infection, such as fever, diarrhea, or hepatomegaly. The clinical presentation of CSM varies widely and can overlap with manifestations of epilepsy, brain tumors, vasculitis, and stroke. A lack of familiarity with its clinical features among both patients and physicians complicates diagnosis and can lead to delays.

Neuroschistosomiasis represents one of the most severe clinical manifestations of schistosomiasis [6]. Spinal cord involvement is predominantly caused by S. mansoni and S. haematobium, whereas cerebral infections are principally associated with S. japonicum [7].

Pathological lesions in CSM typically localize to the parietal, temporal, and occipital lobes, as well as the cerebellum [8]. Notably, the current case exhibited focal lesions concentrated in the parietal lobe, a distribution pattern consistent with the findings of Wang, who reported parietal-occipital involvement in 64% of neuroschistosomiasis cases [9].

The hallmark clinical triad of CSM consists of sensory alterations, headaches, seizure activity, and focal neurological deficits [10]. Crucially, central nervous system (CNS) manifestations arise from granulomatous inflammatory responses to ectopic egg deposition, a pathophysiological process frequently observed in acutely infected patients lacking systemic disease indicators [11].

The present case exemplifies the characteristic clinical progression: initial presentation with nonspecific febrile symptoms followed by development of intracranial space-occupying lesions that show radiological signatures consistent with established characteristics of CSM [12]. The clinical examination revealed the presence of renal calculi, but no established correlation has been demonstrated between CSM and nephrolithiasis in the literature. The pathogenesis of renal calculi in this case was determined to be independent of schistosomal infection. Neuroimaging studies demonstrate that CSM typically manifests as clustered hyperintense foci on MRI, featuring pathognomonic enhancements, including punctate/nodular contrast enhancement, perilesional edema with mass effect, and intralesional heterogeneity [13].

Lu elucidated distinct signal patterns correlating with histopathological stages: larger granulomas exhibit T2-weighted hyperintensity and T1-weighted hypointensity, corresponding to necrotic zones histologically; smaller lesions display iso-/hypointense signals on T2WI and isointense signals on T1WI, indicative of proliferative tissue remodeling [14]. Such multifocal enhancing nodules with periovular granulomatous formations hold critical diagnostic significance. In patients presenting multiple cortical and subcortical enhancing nodules, CSM should be strongly considered when lesions demonstrate strict territorial distribution and are anatomically associated with prominent draining veins.

Current management of CSM lacks a globally standardized protocol, with therapeutic modalities including antiparasitic agents, corticosteroids, and neurosurgical interventions [15]. Praziquantel – a broad-spectrum antischistosomal drug – achieves clinical cure rates of 70–90% through mechanisms involving tegumental disruption, glutathione reserve depletion, and calcium channel modulation. However, its efficacy in alleviating neurological symptoms remains uncertain in neuroschistosomiasis due to variable blood–brain barrier permeability [16]. Corticosteroids are universally applicable across schistosomiasis subtypes, demonstrating dual therapeutic effects by mitigating granulomatous inflammation while potentiating antiparasitic activity [17]. Zhu et al’s retrospective analysis of 166 cases documented symptom resolution in 102 patients following 14–16 days of praziquantel therapy [18].

Neurosurgical management pursues dual objectives: radical excision of schistosomal granulomas and intracranial pressure normalization. Current evidence supports microsurgical resection of pathological lesions combined with posterior fossa decompression as effective therapeutic measures [19]. Although surgical cases constitute <2% of neuroschistosomiasis reports [20], emerging data suggest favorable outcomes with early surgical intervention complemented by praziquantel therapy, even in severe pan-cerebral involvement [21]. Surgical indications primarily target space-occupying lesions with progressive mass effect, as exemplified in this case where microsurgical resection was prioritized due to sustained intracranial hypertension (>30 mmHg) and MRI-confirmed lesion expansion, effectively mitigating cerebral herniation risks [22].

Our patient underwent definitive microsurgical excision of cerebral masses, followed by diagnostic histopathological confirmation and comprehensive therapy combining praziquantel (cumulative dose: 7.2 g), a prednisone anti-inflammatory regimen, and mannitol osmotherapy. Complete neurological recovery was achieved, with serological retesting yielding negative S. japonicum IgG antibodies at 1-year follow-up.

The diagnosis of CSM presents significant clinical challenges. Patients with neuroschistosomiasis frequently exhibit nonspecific systemic manifestations, while conventional fecal examinations detect parasite eggs in only 40–50% of cases [23]. In this reported case, the modified Kato-Katz thick smear technique failed to identify ova, yet serological tests were positive for S. japonicum IgG antibodies. The definitive diagnosis was established through postoperative histopathological examination, which revealed extensive Schistosoma egg deposition accompanied by granulomatous inflammation and microabscess formation in cerebral tissues.

Although the Kato-Katz thick smear technique remains a standard laboratory diagnostic method, the detection of ova in feces, urine, or rectal mucosa is not an obligatory diagnostic criterion [24]. This limitation arises from the ectopic migration of adult worms to the central nervous system via portosystemic shunts, enabling direct oviposition in neural tissues. Furthermore, ancillary investigations such as cerebrospinal fluid analysis and peripheral blood eosinophil counts frequently yield negative results during chronic stages [22]. The diagnostic complexity is compounded by the resemblance of CT/MRI findings to neoplastic lesions such as gliomas, contributing to elevated misdiagnosis rates [11].

The diagnostic process of this case provides valuable experience: in situations where histopathological diagnosis is limited, comprehensive evaluation combining multiple non-invasive indicators is crucial. This underscores the importance of meticulously inquiring about the patient’s residence history, travel history, and history of contact with contaminated water, among other epidemiological data. For unexplained neurological symptoms, especially in patients with an epidemiological exposure history, even mildly elevated eosinophil counts should be considered a warning sign, prompting further consideration of parasitic infection, as this is a simple, cost-effective, and widely accessible hematological indicator. Serological testing offers high sensitivity and specificity, is easy to perform, and requires no invasive procedures, making it a potentially critical tool for early screening and preliminary diagnosis in resource-limited settings.

Given these limitations in neuroimaging and laboratory diagnosis, histopathological identification of Schistosoma eggs with characteristic granulomatous reactions remains the standard method for definitive diagnosis. Clinicians must enhance their awareness of CSM. An integrated diagnostic approach, incorporating travel history to endemic areas, clinical symptoms, serological features, and advanced imaging modalities, must be employed to achieve early diagnosis and initiate timely therapeutic intervention.

Conclusions

This case report highlights the significant health threat posed by CSM, particularly due to S. japonicum, which is endemic to specific regions of China. This case of a 28-year-old man illustrates the diagnostic complexity of CSM, as initial symptoms can mimic other neurological conditions. This similarity underscores the intricate nature of diagnosis and the potential for misdiagnosis. The patient’s journey, from initial headaches to undergoing surgery for a suspected brain tumor, emphasizes the critical importance of a comprehensive diagnostic process that includes serological testing and histopathological examination to confirm the presence of Schistosoma eggs.

This case suggests that healthcare professionals, especially in non-endemic areas, should consider earlier serological testing or a detailed travel history inquiry for unexplained central nervous system space-occupying lesions. This underscores the crucial role of integrating clinical history, imaging studies, laboratory results, and pathological findings in achieving an accurate diagnosis. The successful praziquantel treatment and the patient’s subsequent recovery demonstrate the effectiveness of timely intervention. Continued research and education on schistosomiasis are essential to prevent misdiagnosis and ensure the correct management of this serious parasitic infection.