Intradural cauda equina Candida abscess presenting with hydrocephalus: case report

Abstract

Central nervous system (CNS) candida infections are often associated with a poor prognosis. Typically, CNS candidiasis presents as meningitis or microabscesses. Here, the authors report a patient with a challenging presentation of a CNS Candida infection as a discrete, large cauda equina abscess. The patient initially presented with ventriculomegaly due to fourth ventricular outflow obstruction and a cauda equina mass. The patient was treated with a ventriculoperitoneal shunt and underwent a lumbar laminectomy for exploration of the lumbar lesion. An intradural abscess was encountered during surgery. Fungal wet mount revealed fungal elements and polymerase chain reaction confirmed the presence of Candida albicans. The patient did not have any known predisposition to fungal infections; therefore, the authors performed whole-exome sequencing using peripheral blood mononuclear cell DNA. They found heterozygous missense variants in the following genes: colony-stimulating factor 2 (CSF2) and Ras protein-specific guanine nucleotide-releasing factor 1 (RASGRF1)—genes that have been specifically associated with protection from CNS candidiasis via caspase recruitment domain-containing protein 9 (CARD9) signaling, and phospholipase C gamma 2 (PLCG2)—a lectin receptor involved in candidiasis. The authors’ experience suggests that C. albicans can present as a cauda equina abscess. Hydrocephalus, a result of diffuse arachnoiditis, is a potential complication from intradural fungal abscesses.

Candida albicans is a yeast that is normally encountered on the skin as well as in the respiratory and gastrointestinal tracts. Disseminated C. albicans infections have a tendency to spread to the central nervous system (CNS) in immunocompromised individuals, leading to meningitis and cerebral microabscesses.⁸ Isolated intradural C. albicans abscesses are exceedingly rare.⁶ To our knowledge, C. albicans intradural abscesses had not been encountered within the cauda equina before it was discussed in an earlier report of our patient’s disease course.² In addition, hydrocephalus had not been described to be the presenting feature in a patient with a consoli dated intradural Candida abscess. Here, we report a cauda equina C. albicans abscess that presented with acute hydrocephalus.

Case Report

Ethical Statement

This study was conducted under National Institutes of Health protocol 03-N-0164 (Evaluation and Treatment of Neurosurgical Disorders) and was approved by the Combined Neurosciences Institutional Review Board. Informed consent was obtained from the patient.

History and Examination

A 24-year-old man with a history of substance abuse presented with progressive headaches and nausea in the setting of a 6-month history of chronic low-back pain and bilateral S1 radiculopathy. Physical examination revealed left pupil mydriasis, bilateral upgoing toes, and mild lower extremity dysmetria. Laboratory studies were notable for an elevated C-reactive protein (CRP) of 18.0 mg/L (reference range 0.00–4.99 mg/L) and elevated white blood cell (WBC) count of 10.72 × 10³/μL (reference range 4.23–9.07 × 10³/μL). The patient was afebrile (36.9°C). MRI of the brain demonstrated significant ventriculomegaly, transependymal flow, and abnormal enhancement at the outflow of the fourth ventricle (Fig. 1A). Further imaging of the neuraxis revealed diffuse leptomeningeal enhancement and an enhancing L5 intradural cauda equina mass (Fig. 1B–D). An external ventricular drain was placed to manage the patient’s hydrocephalus. CSF profile revealed an isolated protein level of 550 mg/dl (reference range 12–60 mg/dl) from the lumbar cistern. Ventricular and lumbar CSF cytology and cultures were unremarkable.

FIG. 1. A:

Sagittal T1-weighted postcontrast MR image of the brain demonstrating marked dilation of the lateral, third, and fourth ventricles with abnormal pial enhancement at the base of the fourth ventricle (arrow). B–D: Sagittal T1-weighted postcontrast MRI of the spine demonstrating diffuse leptomeningeal enhancement (arrowheads) and a heterogeneously enhancing, intradural lesion at L5 (arrow).

Operation

Given the diagnostic uncertainty regarding the lumbar lesion, an L3–5 laminectomy with intradural exploration was performed. This revealed marked arachnoiditis with intradural granulation tissue engulfing the caudal nerve roots (Video 1 [00:06]). Intraoperative ultrasound revealed the L5 mass to be a loculated fluid collection (Fig. 2 left). The lesion was fenestrated, thereby expressing purulent material which was sent for culture (Fig. 2 right; Video 1 [00:31]). The abscess was explored, marsupialized, and irrigated.

VIDEO 1.

Download video file ^{(32.2MB, mov)}

Intradural exploration after L3–5 laminectomy demonstrating lesion fenestration and evacuation of purulent material. Orientation: left, caudal; right, rostral. Video from the Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health. This is a US Government work and not under copyright protection in the US.

FIG. 2. Left:

Intraoperative ultrasound (axial) demonstrating a fluid-containing mass at L5 (white arrowheads). D = deep; S = superficial. Right: Intraoperative findings following fenestration of an intradural cauda equina abscess with retracted dura (black arrowheads) and an opened cyst containing purulent fluid (black arrow). C = caudal; R = rostral.

Pathological Findings and Postoperative Course

Fungal elements were found on a wet mount of the purulent material (Fig. 3) and polymerase chain reaction was consistent with Candida albicans. The patient tested negative for human immunodeficiency virus (HIV) and an echocardiogram was unremarkable. Postoperatively, the patient was stable neurologically with reduced radicular pain. As no identifiable cause of his immunosuppression was identified, we performed whole-exome sequencing on the patient. This revealed heterozygous missense mutations in the following genes: colony-stimulating factor 2 (CSF2) (NM_000758.3:c.179T > C; p.I60T), Ras protein-specific guanine nucleotide-releasing factor 1 (RASGRF1) (NM_002891.4:c.1404G > A; p.M468I), and phospholipase C gamma 2 (PLCG2) (NM_002661.4:c.3742A > C; p.K1248Q).

FIG. 3.

Fungal wet mount, Fungi-fluor stain (×1000): abscess fluid demonstrating yeast forms with hyphae, consistent with Candida albicans.

The patient was discharged on a 6-month course of voriconazole. He had a complicated course.² Follow-up MRI approximately 6 weeks postsurgery demonstrated dissemination of the fungal abscess with new enhancing epidural collections in the thoracic and lumbar spine. Voriconazole fungal therapy was changed to amphotericin and flucytosine for 6 weeks, followed by long-term fluconazole suppression, which was ongoing at the time of this report. Subsequent MRI showed resolution of the enhancing fluid collections and CSF fungal cultures were negative, suggesting that the infection was controlled with antifungal therapy. However, the patient presented with worsening myelopathic symptoms including upper and lower extremity weakness, numbness of the hands and feet, and pain in the neck and upper back. He was found to have syringomyelia in the cervical and thoracic spine, obstruction of fourth ventricular outflow, and severe scarring in the subarachnoid space from C1 to C3, and he underwent Chiari decompression and placement of a thoracic syringopleural shunt. He had significant improvement in neurological function following these procedures.

Discussion

This report describes the neurosurgical care and whole-exome sequencing analysis of a patient presenting with a large cauda equina abscess and supplements a previous report of our patient’s postoperative course,² which, to our knowledge, was the first report of a cauda equina Candida abscess presenting with hydrocephalus. Aside from an elevated CRP, our patient did not present with classic signs of infection or meningitis. In conjunction with the patient’s MRI, our original differential diagnosis was a neoplastic etiology including myxopapillary ependymoma or leptomeningeal carcinomatosis. Indeed, sterile CSF with high protein and normal glucose was consistent with a noninfectious process. It was only during surgery that an infectious etiology was clearly identified. The patient was prescribed a 6-month course of voriconazole. Intrathecal antifungal treatment was not used because Candida infections are typically sensitive to treatment with voriconazole. Additionally, intrathecal antifungal treatment can be quite irritating for patients,⁹ and in our patient we thought that such treatment could have exacerbated his arachnoiditis.

Timely diagnosis and treatment are critical for spinal infections. Unfortunately, Candida infections present a diagnostic challenge. MRI is often useful in diagnosing intradural abscesses, but Candida infections may mimic a neoplastic process, making diagnosis more difficult.⁵ Moreover, sterile CSF with elevated protein is not uncommon in Candida cerebral abscesses and spinal infections; such a finding should raise the index of suspicion of a Candida infection in cases where there is diagnostic uncertainty.^5–8 Disseminated C. albicans infections often occur in individuals who are immunosuppressed.⁸ Thus, the diagnosis of C. albicans mandates evaluating an individual for an immunodeficiency.

Whole-exome sequencing of the patient was performed, revealing heterozygous missense variants in several genes involved in candidiasis: CSF2 (novel variant; not documented in gnomAD⁴), RASGRF1, and PLCG2. CSF2 is involved in general hematopoiesis and required for protection from fungal infection in mice,¹ but is also specifically involved in protection from CNS candidiasis in humans via caspase recruitment domain-containing protein 9 (CARD9) signaling.³ CSF2 normally stimulates granulocyte-macrophage colony formation after RASGRF1 complexes with CARD9. However, a previous report showed that the p.Y91H mutant form of CARD9 has reduced interaction with RASGRF1, resulting in reduced CSF2 expression and susceptibility to Candida infection.³ Lastly, the heterozygous missense variant found in PLCG2 could have also contributed to the CNS Candida infection in our patient via immunosuppression. PLCG2 encodes the critical enzyme for dendritic cell signaling of dectin-1, a C-type lectin receptor involved in inflammation during C. albicans infection.¹¹ In an earlier study, dectin-1–deficient leukocytes showed a significantly impaired response to C. albicans infection, demonstrating that dectin-1 is required for normal leukocyte responses to Candida particles.¹⁰

While previous studies have supported the role of CSF2, RASGRF1, and PLCG2 in causing susceptibility to CNS candidiasis,^3,11 further functional and bioinformatic studies are needed to determine if the variants we identified actually influenced immunosuppression in our patient. In this case, no definitive cause of this patient’s C. albicans abscess was identified because, although he acknowledged ingesting and inhaling narcotics, the patient denied intravenous drug use.

Our case highlights an atypical presentation of a fungal intradural abscess and underscores the need for neuraxis imaging in patients with atypical presentations of acute hydrocephalus. Knowledge of Candida infection presentations and the associated diagnostic difficulties could help prevent delayed diagnosis.

ABBREVIATIONS

CARD9

caspase recruitment domain-containing protein 9

CNS

central nervous system

CRP

C-reactive protein

CSF2

colony-stimulating factor 2

PLCG2

phospholipase C gamma 2

RASGRF1

Ras protein-specific guanine nucleotide-releasing factor 1