Treatment of a rare and severe infection of central nervous system by Angiostrongylus cantonensis: A case report

Abstract

BACKGROUND

Angiostrongylus cantonensis-induced acute parasitic infection is a rare food-borne disease in clinical practice. Lack of its specific laboratory markers and subsequent difficulty in detecting pathogens cause high misdiagnosis and missed diagnosis rates.

CASE SUMMARY

A 20-year-old male developed persistent neck and back pain after consuming raw snail meat, followed by urinary retention and low fever. After admission, the patient was misdiagnosed as viral infection and Mycobacterium tuberculosis in central nervous system. After detection of Angiostrongylus cantonensis in blood and cerebrospinal fluid by metagenomics next generation sequencing, albendazole was administered with ceftriaxone and methylprednisolone treatment simultaneously. With effective antiparasitic treatment, the patient weaned from mechanical ventilation successfully and transferred out of intensive care unit for hyperbaric oxygen and rehabilitation treatment.

CONCLUSION

This case highlights the diagnostic challenges of Angiostrongylus cantonensis infection and the importance of advanced sequencing techniques in identifying rare pathogens.

Key Words: Angiostrongylus cantonensis; Cerebrospinal meningitis; Severe infection; Central nervous system; Metagenomics next generation sequencing; Case report

Core Tip: A 20-year-old male developed persistent neck and back pain, urinary retention, and low fever after consuming raw snail meat. Initially misdiagnosed with viral infection and Mycobacterium tuberculosis in the central nervous system, the patient was later confirmed to have Angiostrongylus cantonensis infection via metagenomics next-generation sequencing. Effective antiparasitic treatment with albendazole, ceftriaxone, and methylprednisolone led to successful weaning from mechanical ventilation and transfer out of the intensive care unit for hyperbaric oxygen and rehabilitation treatment. This case highlights the diagnostic challenges of Angiostrongylus cantonensis infection and the importance of advanced sequencing techniques in identifying rare pathogens.

INTRODUCTION

Angiostrongylus cantonensis-induced acute parasitic infection is a food-borne zoonotic disease in humans[1]. Angiostrongylus cantonensis has neurotropic larvae, primarily resulting in manifestations such as cerebral meningitis, spinal meningitis, encephalitis, or myelitis with eosinophilia, also known as eosinophilic meningitis or eosinophilic meningoencephalitis[2]. It is prevalent worldwide, especially in the Asia-Pacific region, Europe, and South Asia. In the Asia-Pacific region, Thailand and Malaysia are highly endemic, followed by China, Vietnam, the Philippines, and Hawaii[3]. In China, it is predominantly found in southeastern coastal areas such as Guangdong Province, Fujian Province, and Taiwan, and some cases have also been reported in Beijing, Wenzhou, and Dali due to local outbreaks caused by the consumption of raw Pomacea canaliculate[2,4-6]. Due to nonspecific clinical manifestations, low sensitivity of etiological evidence, and difficulty in detecting parasitic bodies, the misdiagnosis and missed diagnosis rates of this acute parasitic infection are high. The clinical features of angiostrongyliasis cantonensis closely resemble those seen in other prevalent central nervous system (CNS) infections, such as viral, bacterial, and tuberculous meningitis, which increases the likelihood of misdiagnosis during the evaluation process. An increase in the white blood cell count within the cerebrospinal fluid (CSF) is a common occurrence across a variety of CNS infections. A distinctive attribute of angiostrongyliasis cantonensis is that eosinophils constitute more than 10% of the CSF, a finding that is relatively uncommon in other forms of meningitis. Nonetheless, due to the nonspecific nature of the clinical presentations associated with angiostrongyliasis cantonensis and the challenges associated with pathogen detection, establishing a definitive diagnosis based solely on standard clinical findings and laboratory assessments can be quite difficult[7]. Therefore, it is crucial to further understand the characteristics of the disease and standardize its diagnosis and treatment. Herein, we report a rare and severe infection of CNS by Angiostrongylus cantonensis, for references of clinical physicians in differentiation and diagnosis of this condition in the future.

CASE PRESENTATION

Chief complaints

Persistent neck and back pain accompanied by fever for 10 days after exercise on October 13, 2023.

History of present illness

The 20-year-old man took diclofenac sodium for pain relief, but it was ineffective. On the 2^nd day, urinary retention and low fever occurred. Treatment with “cold medications” on his own did not improve the condition, and he experienced weakness and difficulty walking. He then presented to another hospital with a peak fever of 39.6 °C, accompanied by dizziness, headache, and visual ghosting. The pain, pronounced at the occiput, was intermittent and accompanied by chills and shivering, without nausea or vomiting. A cervical spine magnetic resonance imaging (MRI) suggested abnormal long-segment signals in the spinal cord, while a brain MRI showed suspicious intracranial abnormal signals. A lumbar puncture indicated elevated intracranial pressure up to 400 mmH₂O (1 mmH₂O = 0.0098 kPa). The CSF appeared clear and transparent, with multinucleated cells of 46.7%, monocytes of 53.3%, and a white blood count of 471 × 10⁶/L. The CSF biochemistry showed glucose at 1.94 mmol/L (decrease), chloride at 113.1 mmol/L, positive Pandey’s test, total protein at 891.2 mg/L (increase), lactate at 2.29 mmol/L, and negative Mycobacterium tuberculosis (M. tuberculosis) DNA. After dehydration for intracranial pressure reduction and viral and bacterial treatment with acyclovir and cefotaxime, the patient’s body temperature lowered with intermittent low fevers. Symptoms such as headache and visual ghosting persisted, and the muscle strength of both lower limbs was too poor to walk, manifesting as paraplegia.

History of past illness

The patient has no history of diabetes, hypertension, or any other significant diseases noted in past physical examinations. He has no known allergies to food or medications, and no history of blood transfusions or surgeries.

Personal and family history

Personal history: The patient is a 20-year-old unmarried male college student who has been residing in Danzhou City, Hainan Province, for an extended period. He regularly engages in physical exercise and has no history of high-risk sexual behaviors.

Family history: There is no history of clustered or hereditary diseases in the patient’s family.

Physical examination

Vital signs: Admitted to the hospital on October 23, 2023. Temperature was 37.3 °C; pulse was 85 beats/minute; respiration was 19 breaths/minute and blood pressure was 115/68 mmHg (1 mmHg = 0.133 kPa).

Neurology physical examination: Acutely ill facies; active position and alert state. The muscle strength in all four limbs were grade 1 +, with no abnormalities observed in muscle tone. Tendon reflexes of bilateral biceps and triceps were normal, as were bilateral knee and ankle reflexes. Babinski’s reflex was negative bilaterally. Eyeballs were normal, with equal and round pupils measuring approximately 3 mm in diameter, sensitive to light. There was no visual ghosting, visual field defects, visual distortions, or other remarkable findings.

On October 25, 2023, a neurology consultation was requested for special physical examination. The patient presented with mild drowsiness and fluent speech. Pupils were equal and round, with present light reflexes. However, bilateral eyeball abduction was defective, with approximately 3 mm of sclera visible between the outer canthus and the limbus. Horizontal nystagmus was noted in both eyes. Muscle strength was grade 3 + in both upper limbs and grade 3 in both lower limbs. There were no significant abnormalities in deep or superficial sensation. Tendon reflexes in both upper limbs were symmetrically elicited (++), while those in both lower limbs were reduced.

Laboratory examinations

After admission on October 23, 2023, blood tests were conducted (Table 1). A preliminary diagnosis of intracranial infection was considered based on the medical history, symptoms, signs, and examinations at another hospital (abnormal long-segment signals within spinal cord on cervical spine MRI, CSF pressure of 400 mmH₂O on lumbar puncture). In our hospital, a lumbar puncture was performed again, measuring CSF pressure to be greater than 300 mmH₂O, and CSF samples were sent for testing. CSF testing findings were conducted. Venous blood immunoglobulin + complement testing showed that IgG was 1770 mg/dL↑ and IgE was 112 IU/mL, and other indicators were within the normal range.

Table 1 Summary of blood test results on admission.

Item	Result	Trend
White blood cell count (109/L)	11.46	Indicates an increase
Neutrophils	0.660	No significant change or not mentioned
Lymphocytes (109/L)	0.196	Indicates a decrease
Monocytes (109/L)	0.089	Indicates an increase
Eosinophils (109/L)	0.049	No significant change or not mentioned
D-dimer (ng/mL)	2209	No significant change or not mentioned
International normalized ratio	1.43	Indicates an increase
Plasma prothrombin time (second)	15.4	Indicates an increase
Plasma prothrombin activity (%)	60	Indicates a decrease
Inflammatory indicators	Normal	No significant change or not mentioned
Electrolytes	Normal	No significant change or not mentioned

Further CSF microbiological investigations are planned, including tests for tuberculosis, cytology, specific pathogens, and comprehensive pathogen metagenomics, to establish a definitive diagnosis through repeated examinations.

Despite negative pathogen results in multiple CSF examinations, the CSF was clear with low glucose and high protein levels, suggestive of a high probability of M. tuberculosis infection. However, all tuberculosis-related tests returned negative results, including tests for M. tuberculosis nucleic acid, M. tuberculosis-specific cell-mediated immunity, tuberculosis antibodies, M. tuberculosis and rifampicin-resistant genes, adenosine deaminase, M. tuberculosis amplification fluorescence, and tuberculin purified protein derivative. Rheumatological and other relevant tests were also negative, including tests for autoantibody profiles (14 items), antimitochondrial antibodies, antineutrophil cytoplasmic antibodies, and leptospira antibodies. In-house etiological targeted next generation sequencing (tNGS) tests for CSF were negative (Table 2 and Table 3).

Table 2 Summary of cerebrospinal fluid test results.

Item	October 23, 2023	October 27, 2023	October 29, 2023	November 06, 2023	November 08, 2023
Routine	Colorless and transparent; total cell count: 1254 × 106/L; total WBC: 954 × 106/L; multinucleated to mononucleated cell ratio: 1:1; qualitative protein test: Positive	Colorless and transparent; total cell count: 187 × 106/L; total WBC: 182 × 106/L; multinucleated to mononucleated cell ratio: 0.85; qualitative protein test: Positive	Colorless and transparent; total cell count: 147 × 106/L; total WBC: 108 × 106/L; multinucleated to mononucleated cell ratio: 1:9; qualitative protein test: Positive	Light yellow and slightly turbid; total cell count: 82 × 106/L; total WBC: 79 × 106/L; multinucleated to mononucleated cell ratio: 0.47; qualitative protein test: Positive	Light yellow and transparent; total cell count: 142 × 106/L; total WBC: 142 × 106/L; multinucleated to mononucleated cell ratio: 0.45; qualitative protein test: Positive
Biochemical test	Glu 2.71 mmol/L (decrease); chloride 1134 mmol/L (decrease); protein 790 mmol/L (increase)	Glu 2.08 mmol/L (decrease); chloride 116 mmol/L (decrease); protein 685 mmol/L (increase)	Glu 3.51 mmol/L; chloride 121 mmol/L; protein 412 mmol/L (increase)	Glu 2.49 mmol/L (decrease); chloride 1155 mmol/L (decrease); protein 1000 mmol/L (increase)	Glu 2.9 mmol/L; chloride 113 mmol/L (decrease); protein 936 mmol/L (increase)
Ig determination	IgA 1.0 mg/dL (increase); IgG 10.2 mg/dL (increase); IgM 4.7 mg/dL (increase)	IgA 4.0 mg/dL (increase); IgG 22.5 mg/dL (increase); IgM 8.4 mg/dL (increase)	IgA 4.0 mg/dL (increase); IgG 15 mg/dL (increase); IgM 5.8 mg/dL (increase)	IgA 2.4 mg/dL (increase); IgG 32.7 mg/dL (increase); IgM 0.3 mg/dL (increase)	IgA 2.0 mg/dL (increase); IgG 33.2 mg/dL (increase); IgM 0.2 mg/dL (increase)
TORCH	Negative	Negative	Negative	Negative	Negative
Pathogen detection	Negative	Negative	Negative	Negative	Negative
Bedside ROSE	Absent	Absent	No bacteria, fungi, or parasites found. Predominantly mononuclear cells	No bacteria, fungi, or parasites found. Predominantly mononuclear cells with a few eosinophils	No bacteria, fungi, or parasites found. Predominantly mononuclear cells with a few eosinophils
M. tuberculosis nucleic acid PCR test	Absent	Absent	Absent	Negative	Negative
M. tuberculosis and rifampicin resistance gene testing	Absent	Absent	Negative	Negative	Absent
NGS test in this hospital	Negative	Negative	Negative	Negative	Absent
KingMed NGS test	Absent	Absent	Absent	Absent	Angiostrongylus cantonensis (sequences 4643)

Glu: Glucose; Ig: Immunoglobulin; TORCH: Toxoplasma, other pathogens, rubella virus, cytomegalovirus, and herpes simplex virus; NGS: Next-generation sequencing; M. tuberculosis: Mycobacterium tuberculosis; PCR: Polymerase chain reaction; ROSE: Rapid on site evaluation; WBC: White blood cell.

Table 3 Summary of cerebrospinal fluid test results.

Item	November 11, 2023	November 16, 2023	November 22, 2023	November 30, 2023	December 19, 2023
Routine	Colorless and slightly turbid; total cell count: 506 × 106/L; total WBC: 491 × 106/L; multinucleated to mononucleated cell ratio: 0.75; qualitative protein test: Positive	Colorless and transparent; total cell count: 171 × 106/L; total WBC: 145 × 106/L; multinucleated to mononucleated cell ratio: 0.27; qualitative protein test: Positive	Colorless and transparent; total cell count: 90 × 106/L; total WBC: 88 × 106/L; multinucleated to mononucleated cell ratio: 0.45; qualitative protein test: Positive	Colorless and transparent; total cell count: 65 × 106/L; total WBC: 59 × 106/L; multinucleated to mononucleated cell ratio: 0.08; qualitative protein test: Positive	Colorless and transparent; total cell count: 252 × 106/L; total WBC: 88 × 106/L; multinucleated to mononucleated cell ratio: 0.08; qualitative protein test: Positive
Biochemical test	Glu 2.36 mmol/L (decrease); chloride 1183 mmol/L (decrease); protein 980 mmol/L (increase)	Glu 2.51 mmol/L (decrease); chloride 1195 mmol/L; protein 1023 mmol/L (increase)	Glu 3.22 mmol/L (decrease); chloride 1209 mmol/L; protein 574 mmol/L (increase)	Glu 2.87 mmol/L; chloride 121 mmol/L; protein 604 mmol/L (increase)	Glu 3.02 mmol/L; chloride 1233 mmol/L; protein 412 mmol/L (increase)
Ig determination	IgA 1.8 mg/dL (increase); IgG 33.5 mg/dL (increase); IgM 9.8 mg/dL (increase)	IgA 1.0 mg/dL (increase); IgG 32.1 mg/dL (increase); IgM 16.8 mg/dL (increase)	IgA 0.5 mg/dL; IgG 19.2 mg/dL (increase); IgM 5.2 mg/dL (increase)	IgA 2.4 mg/dL (increase); IgG 17.9 mg/dL (increase); IgM 0.3 mg/dL (increase)	IgA 1.2 mg/dL (increase); IgG 10 mg/dL (increase); IgM 1.7 mg/dL (increase)
TORCH	Absent	Absent	Absent	Absent	Absent
Pathogen detection	Negative	Negative	Negative	Negative	Negative
Bedside ROSE	No bacteria, fungi, or parasites found. Predominantly mononuclear cells with eosinophils being approximately 40%	No bacteria, fungi, or parasites found. Predominantly mononuclear cells with eosinophils being approximately 11.1%	Absent	Absent	Absent
M. tuberculosis nucleic acid PCR test	Absent	Absent	Absent	Absent	Absent
M. tuberculosis and rifampicin resistance gene testing	Absent	Absent	Absent	Absent	Absent
NGS test in this hospital	Absent	Negative	Absent	Absent	Absent
KingMed NGS test	Absent	Absent	Absent	Angiostrongylus cantonensis (sequences 10429)	Angiostrongylus cantonensis (sequences 1003)

Glu: Glucose; Ig: Immunoglobulin; TORCH: Toxoplasma, other pathogens, rubella virus, cytomegalovirus, and herpes simplex virus; NGS: Next-generation sequencing; M. tuberculosis: Mycobacterium tuberculosis; PCR: Polymerase chain reaction; ROSE: Rapid on site evaluation; WBC: White blood cell.

Imaging examinations

Computed tomography scans showed no significant head abnormality, mild pneumonia, partial colon dilatation and pneumatosis, and mild pelvic fluid accumulation. No other remarkable abnormalities were noted. Electrocardiogram and cardiac ultrasound results were unremarkable. Cervical spine MRI scans, without and with contrast, revealed enhancement of the cerebral pia mater in cerebellar hemisphere, brainstem, and upper medulla oblongata, consistent with cerebrospinal meningitis (Figure 1A and B). Brain MRI findings showed no abnormal signals (Figure 1C). Based on the imaging results, there is a high likelihood of CNS infection, with a confirmed diagnosis of cerebral meningitis and myelitis. However, the causative pathogen remains unidentified.

Figure 1 Magnetic resonance imaging scans of cervical spine and cranial region. A: Cervical spine magnetic resonance imaging (MRI) (with and without contrast, October 25, 2023) showing enhancement of the cerebral pia mater in the cerebellar hemisphere and brainstem; B: Cervical spine MRI (with and without contrast, October 25, 2023) showing enhancement of the cerebral pia mater at the edge of the upper medulla oblongata; C: Cranial MRI (without contrast and with diffusion weighted imaging, October 24, 2023) showing no intracranial high signal on T2 flair coronal view.

MULTIDISCIPLINARY EXPERT CONSULTATION

Neurology specialists were repeatedly consulted to evaluate the patient’s level of consciousness and brain function. Ophthalmology consultations did not reveal any parasites in the anterior segments or conjunctivae.

FINAL DIAGNOSIS

On November 09, 2023, the KingMed laboratory reported as follow: Metagenomics next generation sequencing (mNGS) test detected Angiostrongylus cantonensis, with a sequence count of 35 in whole blood (a relative abundance of 8.58%), and with a sequence count of 4643 in CSF (a relative abundance of 94.43%). Additionally, the CSF indicated an increase in eosinophils, supporting the diagnosis of parasitic infection. Following the detection of Angiostrongylus cantonensis in both the CSF and blood, the diagnosis of CNS infection by Angiostrongylus cantonensis and cerebrospinal meningitis was confirmed.

TREATMENT

After hospitalization, the patient received a combination of acyclovir and ceftriaxone for common viral and bacterial infections. Symptomatic supportive therapies were also administered including acid suppression, dehydration with mannitol, immunoglobulin injection, maintenance of water-electrolyte and acid-base balance. Despite these measures, the patient’s mental status continued to deteriorate. Mannitol dehydration was intensified, yet oxygen saturation continued to decline, and vital signs remained unstable. Consequently, on October 28, 2023, the patient was intubated and connected to a mechanical ventilator for assisted breathing. Additionally, methylprednisolone 500 mg was administered for a pulse therapy. On October 29, 2023, a lumbar cistern catheter was placed for drainage. On October 30, 2023, an empiric four-drug anti-tuberculosis regimen (isoniazid + rifampicin + ethambutol + pyrazinamide) was initiated for one week. However, the patient still had intermittent fevers and no improvement in symptoms. Given the absence of positive findings for tuberculosis infection, anti-tuberculosis treatment was discontinued. On November 09, 2023, albendazole 0.4 g was administered every 8 hours upon detection of Angiostrongylus cantonensis. Meropenem, clarithromycin, amikacin, and rifampicin were discontinued, while ceftriaxone was maintained. The dosage of methylprednisolone was increased to 40 mg twice daily. Subsequently, repeated CSF tests were conducted, and relevant departments were consulted to assist in finding evidence of parasites using available laboratory methods.

OUTCOME AND FOLLOW-UP

The therapy was adjusted accordingly based on expert consensus. After 10 days of treatment, cranial MRI tests, without contrast and with diffusion weighted imaging (DWI), were performed on November 20, 2023. Findings showed multiple patchy and slightly long T1 and T2 signal lesions in bilateral frontal, temporal, parietal, occipital, and insular lobes, and periventricular area; T2 Flair imaging showed slightly high signals, DWI showed no abnormal high signals, and apparent diffusion coefficient mapping showed no significant decrease in signal intensity (Figure 2). The lumbar cistern drain was removed on November 24, 2023. After anti-parasitic treatment, the patient’s general condition gradually improved, intermittent ventilator weaning was initiated, and the endotracheal tube was removed on December 14, 2023. Cranial MRI tests without contrast and with DWI were conducted again on December 18, 2023, which showed a significant reduction and shrinkage of the multiple patchy high signal lesions in the frontal, temporal, parietal, and occipital white matter in sagittal position on T2 flair imaging compared with before (Figure 3). A neurological examination on December 19, 2023 revealed that the patient was alert and unable to open and close eyes as instructed, with facial expression of pain. Bilateral pupils were equal and round, approximately 3 mm in diameter, sensitive to light; eyes were misaligned, with left eye adducted; no significant response to painful stimuli was noted on all limbs, with positive (+) pathological signs bilaterally. On December 20, 2023, the patient was transferred out of the intensive care unit for hyperbaric oxygen and rehabilitation treatment. Before discharge, he underwent two additional NGS tests. On December 3, 2023, Angiostrongylus cantonensis was detected in blood with a sequence count of 3 and a relative abundance of 5.26%; similarly, Angiostrongylus cantonensis was detected in CSF with a sequence count of 10429 and a relative abundance of 99.11%. On December 20, 2023, Angiostrongylus cantonensis was detected in CSF with a sequence count of 1003 and a relative abundance of 95.66%. Apart from the NGS results, multiple CSF tests did not find any parasites. On November 11, 2023, 150 mL of CSF was collected from lumbar cistern drainage to search for parasites. On November 14, 2023, the cytology examination findings reported that hematoxylin and eosin staining showed a large amount of pink amorphous material, with some chronic inflammatory cells and eosinophils, but no parasite bodies or eggs were found (Figure 4). A follow-up on January 17, 2024 revealed that the patient was alert and capable of verbal communication. He had started oral intake independently and continued rehabilitation for limb muscle strength. On April 11, 2024, the patient was alert and able to communicate normally. He could eat by himself, and the strength and motor sensation functions of his upper limbs had returned to normal. However, he was still unable to manage bladder and bowel functions independently, and his lower limb movement was not strong enough to stand.

Figure 2 Magnetic resonance imaging scans of brain with diffusion weighted imaging (November 20, 2023). Multiple abnormal enhancement signals (linear enhancement signals) observed in the pia mater and the edge of medulla oblongata. A: T2 flair coronal images showed multiple patchy lesions in the bilateral frontal lobe and periventricular white matter; B: T2 flair sagittal images showed multiple patchy and round, slightly high signals in the white matter of bilateral frontal, temporal, parietal, occipital lobes.

Figure 3 Magnetic resonance imaging scans of brain with diffusion weighted imaging (December 18, 2023). Multiple patchy and round, slightly high signals in the white matter of bilateral frontal, temporal, parietal, occipital lobes, and periventricular area significantly decreased and shrunken compared with before. A: T2 flair coronal view; B: T2 flair sagittal view.

Figure 4 Cerebrospinal fluid cytology results. Numerous pink amorphous materials observed, along with some chronic inflammatory cells and eosinophils. No parasitic organisms or eggs were detected. A: Hematoxylin-eosin × 10; B: Hematoxylin-eosin × 40.

DISCUSSION

In 1935, Chinese scholar Chen XT discovered Angiostrongylus cantonensis in the lungs of house rats and brown rats in Guangzhou and named it according to nomenclature conventions. Subsequently, some Angiostrongylus cantonensis infection cases have been reported[8]. In 1984, He et al[9] identified immature Angiostrongylus cantonensis larvae in the CSF of a patient with cerebral meningitis, confirming the first case of Angiostrongylus cantonensis infection in the Chinese mainland[9]. With the spread of intermediate hosts (e.g., terrestrial snails and freshwater snails) and increased consumption of snail meat, the incidence of Angiostrongylus cantonensis infection has been on the rise. Early symptoms mainly include fever, persistent headache, generalized body or limb pain, neck stiffness, and sensory abnormalities. Some patients may also experience psychiatric symptoms, vomiting, rash, hyperalgesia, or coma. The headache is often severe, but signs of meningeal irritation are mild or absent, and some cases may be asymptomatic carriers[10]. Coma in patients often indicates severe infection, with poor prognosis and critical condition. The diagnosis and treatment of this severe case of CNS infection by Angiostrongylus cantonensis poses several challenges.

Firstly, despite typical clinical presentations according to expert consensus, the disease was rare and progressed rapidly in this patient’s imaging studies. Initially, the patient was lethargic but able to communicate on admission. The first cranial MRI scan without contrast and with DWI showed no significant abnormalities. However, subsequent cranial MRI scans without contrast and with contrast on October 28, 2023 revealed multiple patchy enhanced signals along the cerebral pia mater and the edge of the medulla oblongata, without any abnormal intracranial signals. Following the diagnosis on November 10, 2023 and 10 days of treatment, follow-up cranial MRI scans without contrast and with DWI on November 20 showed multiple patchy, slightly long T1 and T2 signals in bilateral frontal, temporal, parietal, occipital, and insular lobes and periventricular area, with slightly high T2 flair signals.

Secondly, the other difficult aspect of the diagnosis was the consistently negative results of various tests, particularly multiple routine CSF microbiological tests, including bacterial and fungal smears, routine cultures, liquid-based parasite eggs, and CSF cytology, which failed to detect any parasite bodies. The elevation of eosinophils in both blood and CSF is important for diagnosis of this disease[11], although eosinophils may be normal in rare cases[12]. In this patient, the eosinophil count was not elevated in the CSF and was normal in the blood during the early stage, atypical in the laboratory findings. Additionally, multiple consultations with ophthalmologists to examine the anterior segments and conjunctivae did not reveal any parasites. Both the hospital laboratory and partnering laboratory had no serum antibodies against Angiostrongylus cantonensis, failing to confirm the diagnosis through enzyme-linked immunosorbent assay. Ultimately, the diagnosis was established by detecting Angiostrongylus cantonensis gene sequences in both the whole blood and CSF using the mNGS technique.

Thirdly, regarding treatment, there is no updated clinical treatment plan for Angiostrongylus cantonensis infection since the 2006 guidelines in China, which recommends albendazole at a dose of 20 mg/kg/day in three divided doses for 7 to 10 days, primarily for mild cases[2]. However, in this severe case, the patient’s symptoms did not significantly improve after antiparasitic treatment, and albendazole was thus continued for over a month.

Fourthly, conventional antigen-antibody testing can also confirm Angiostrongylus cantonensis infection, but its antibodies are not routinely kept in clinical laboratories and testing companies due to its rarity and difficulty in discovering antibodies. Recently, mNGS has rapidly developed and been applied in the detection of infectious pathogens, improving the accuracy and timeliness of disease diagnosis. However, there are still many issues regarding its clinical application[13]. As mNGS is a novel detection method, its testing technique, the authenticity and stability of its results, and the interpretation of those results are not fully standardized, requiring careful interpretation. In this case, tNGS tests were conducted in the other department of this hospital. Unfortunately, while the sequencing genome identification library covers over 354 common pathogens, it did not include the genome of Angiostrongylus cantonensis. Relying on this result when the diagnosis was uncertain may have affected the accuracy and timeliness of the final diagnosis. It also suggests that in future challenging diagnoses, the NGS genome identification library should be confirmed to include data on the genomes of suspected non-common or atypical pathogens.

Lastly, thorough inquiry into the medical history is also crucial for the diagnosis of this disease. In this case, the patient initially denied any history of dining out due to personal reasons. However, after communicating with his colleagues and family members, we found that on September 16, 2023, the patient visited a seafood market and had purchased and barbecued with snail meat that evening. On September 22, 2023, he experienced vomiting and neglected it. Several days later, the patient experienced arm and back pain. Accurate medical history during the initial hospitalization should be provided for the prevention and diagnosis of infectious diseases, especially for rare or emerging conditions.

CONCLUSION

In conclusion, the infection of CNS by Angiostrongylus cantonensis is difficult to be recognized and cured. When conventional clinical methods fail to identify the culprit, genetic testing methods should be considered. Currently, consensus on the diagnosis and treatment of Angiostrongylus cantonensis infection has long not been updated, and the treatment experience for severe infection by Angiostrongylus cantonensis is absent, so many issues warrant further research regarding the dosage, duration, criteria for discontinuation of albendazole treatment, steroid regimens, immunoglobulin regimens, and whether a decrease in mNGS sequence count can be used as an indication for discontinuation of treatment.

ACKNOWLEDGEMENTS

We appreciate the help of Chen ZY, Wang BT (Department of Radiology), Liu Y (Department of Pathology), Zhou YM (Department of Information Technology) from Hainan Hospital of Chinese PLA General Hospital. We thank Chen SY for editing the English text of a draft of this manuscript.