Neurosyphilis with ocular involvement and normal magnetic resonance imaging results affirmed by metagenomic next-generation sequencing

Abstract

The rapid and accurate identification of pathogenic agents is the key to guide clinicians on diagnosis and medication, especially for intractable diseases, such as neurosyphilis. It is extremely challenging for clinicians to diagnose neurosyphilis with no highly sensitive and specific test available. It is well known that the early transmission and immune evasion ability of Treponema pallidum have earned it the title of “stealth pathogen.” Neurosyphilis has complex clinical manifestations, including ocular involvement, which is infrequent and often overlooked, but its neuroimaging results may be normal. Therefore, it is important to find a new test that can detect the presence or absence of Treponema pallidum immediately for the diagnosis of neurosyphilis. We reviewed all the patients admitted to the Sichuan Provincial People’s Hospital between 2021 and 2022 who had ocular involvement and whose clinical samples were examined via metagenomic next-generation sequencing (mNGS), and we found 10 candidates for further analysis. The results of magnetic resonance imaging (MRI) were normal for four patients, and three of them met the diagnostic criteria for neurosyphilis confirmed by mNGS. In addition, the results of mNGS from the three patients were further validated using polymerase chain reaction (PCR). Five of the 10 patients had diplopia manifestations; two (20%) experienced abducens nerve palsies, two (20%) had eyelid drooping, and one (10%) had decreased vision. One of the 10 patients (10%) who was HIV positive and five patients had abnormal MRI results. To our knowledge, Treponema pallidum was detected by mNGS in patients with ocular involvement and normal MRI results for the first time. Given this situation, we recommend mNGS as a potential and supplementary tool for the diagnosis and differential diagnosis of neurosyphilis.

An Incidental Diagnosis of Neurosyphilis: A Case Report

“…These conditions lead to loss of visual acuity and other complications such as glaucoma, cataracts, macular edema, retinal detachment, retinal vessel occlusion, and choroidal neovascularization [ 9 ]. Many patients with ocular involvement do not show any evidence of disease in their imaging, which can lead to difficulty in diagnosis [ 10 ].…”

Neurosyphilis: insights into its pathogenesis, susceptibility, diagnosis, treatment, and prevention

“…Pham et al found T. pallidum in brain tissue, which was confirmed by 16S ribosomal RNA sequencing ( 22 ). Additionally, metagenomic next-generation sequencing (mNGS) detected T. pallidum nucleic acids in the CSF at low levels ( 23 ). These studies provide substantive evidence for the neuroinvasive capacity of T. pallidum .…”

“…It has been demonstrated in rabbit models, mouse models, and human subjects that T. pallidum is capable of invading the CNS early in the disease (21). Pham et al found T. pallidum in brain tissue, which was confirmed by 16S ribosomal RNA sequencing (22). Additionally, metagenomic next-generation sequencing (mNGS) detected T. pallidum nucleic acids in the CSF at low levels (23).…”

Editorial: Neurosyphilis: epidemiology, clinical manifestations, diagnosis, immunology and treatment

“…Although the performance of molecular assays is unsatisfactory, given that a negative PCR test may not rule out Tp infection, the application of assays serves as a potential supplementary tool for the diagnosis and differential diagnosis of neurosyphilis ( 5 ). This option requires consideration that CRISPR-based approaches may increase the clinical sensitivity ( 6 ) and Tp can be detected in CSF by metagenome sequencing (mNGS) in patients ( 7 ).…”