Characteristic Profiling of Soluble Factors in the Cerebrospinal Fluid of Patients With Neurosyphilis.

BACKGROUND: Soluble inflammatory factors in the cerebrospinal fluid (CSF) of patients with neurosyphilis have been investigated with low-throughput technology. This study aimed to illustrate the characteristics of soluble factor profiles in CSF of patients with neurosyphilis. METHODS: We measured the concentrations of 45 cytokines, chemokines, and growth factors in CSF from 112 untreated syphilis cases, including latent syphilis (LS), asymptomatic neurosyphilis (ANS), meningeal neurosyphilis (MNS), meningovascular neurosyphilis (MVNS), paralytic dementia (PD), and ocular syphilis (OS). RESULTS: Thirty-three differentially expressed soluble factors (DeSFs) were categorized into 3 clusters. DeSF scores of clusters 1 and 2 (DeSFS1 and DeSFS2) were positively correlated with elevated neopterin and neurofilament light subunit (NF-L) concentration, respectively. DeSF scores of cluster 3 were positively correlated with white blood cells, protein, NF-L, and neopterin. Patients with LS, ANS, and OS exhibited an overall lower abundance of DeSFs. Patients with PD exhibited significantly increased levels of clusters 1 and 3, and the highest total DeSF score, whereas patients with MNS and MVNS showed enhanced levels of cluster 2. Receiver operating characteristic analysis revealed that DeSFS1 effectively discriminated PD, and DeSFS2 discriminated MNS/MVNS with high accuracy. CONCLUSIONS: Patients with neurosyphilis at different stages have distinctive patterns of soluble factors in CSF, which are correlated with immune status and neuronal damage.

Novel and characteristic radiological features of neurosyphilis: a case series.

BACKGROUND: Treponema pallidum can invade the central nervous system (CNS) early in its infection, causing neurosyphilis. Neurosyphilis typically presents with meningovasculitis in the acute or subacute phase, while tabes dorsalis and dementia paralytica are classical conditions in the later stages. However, syphilis is often misdiagnosed as other conditions such as tumors or autoimmune diseases including vasculitis and encephalitis, which is why the condition is known as "The Great Mimicker." The increasing incidence of syphilis in recent years emphasizes the importance of early diagnosis and treatment; however, its multiple clinical manifestations impose diagnostic challenges for clinicians because it resembles other diseases. In this case series, we present the impressive manifestations of neurosyphilis through three unique radiological presentations. CASE PRESENTATION: Case 1 details optic nerve involvement in an HIV-positive male, where MRI and fundoscopic findings confirmed syphilitic optic neuritis. Case 2 describes a patient in her pregnancy initially suspected of acoustic neuroma on MRI, later diagnosed with syphilitic gumma affecting the inner ear canal. Case 3 is a young male with clinical features mimicking temporal arteritis, ultimately identified as skull osteomyelitis secondarily causing inflammation of the musculus temporalis and meningitis. CONCLUSIONS: These cases underscore the necessity of considering syphilis in differential diagnoses, given the diversity of its clinical presentations. Radiology plays an important role in avoiding unnecessary interventions. The increasing prevalence of recurrent syphilis imposes diagnostic challenges, emphasizing the importance of the early diagnosis and treatment of neurosyphilis by clinicians.

Clinical parameter-based prediction model for neurosyphilis risk stratification.

Accurately predicting neurosyphilis prior to a lumbar puncture (LP) is critical for the prompt management of neurosyphilis. However, a valid and reliable model for this purpose is still lacking. This study aimed to develop a nomogram for the accurate identification of neurosyphilis in patients with syphilis. The training cohort included 9,504 syphilis patients who underwent initial neurosyphilis evaluation between 2009 and 2020, while the validation cohort comprised 526 patients whose data were prospectively collected from January 2021 to September 2021. Neurosyphilis was observed in 35.8% (3,400/9,504) of the training cohort and 37.6% (198/526) of the validation cohort. The nomogram incorporated factors such as age, male gender, neurological and psychiatric symptoms, serum RPR, a mucous plaque of the larynx and nose, a history of other STD infections, and co-diabetes. The model exhibited good performance with concordance indexes of 0.84 (95% CI, 0.83-0.85) and 0.82 (95% CI, 0.78-0.86) in the training and validation cohorts, respectively, along with well-fitted calibration curves. This study developed a precise nomogram to predict neurosyphilis risk in syphilis patients, with potential implications for early detection prior to an LP.

Enhancing clinical awareness: retrospective analysis of neurosyphilis cases and diagnostic predictors for early recognition and treatment.

OBJECTIVE: This is a retrospective analysis of clinical data from individuals diagnosed with neurosyphilis, aiming to enhance healthcare professionals' understanding of the disease and expedite early diagnosis and intervention. METHODS: A retrospective analysis was conducted on the clinical records of 50 patients who received a diagnosis of symptomatic neurosyphilis and were admitted to the Neurology Department during the period spanning January 2012 to December 2022. RESULTS: Clinical manifestations encompassed diverse phenotypes, with syphilitic meningitis accounting for 16% of cases, characterized by symptoms such as headache, blepharoptosis, paralysis, blurred vision, and tinnitus. Meningovascular syphilis presented in 36% of cases, exhibiting episodic loss of consciousness, limb numbness, and limb convulsion. Paralytic dementia manifested in 36% of cases, featuring symptoms such as memory loss, sluggish response, and slow movement. Tabes dorsalis was observed in 12% of cases, presenting with weakness, numbness, and staggering. Routine cerebrospinal fluid (CSF) analysis indicated abnormal white blood cell counts in 60% of patients, while biochemical testing revealed abnormal protein content in 52% of patients. Notably, statistically significant differences were observed between patients with interstitial and parenchymatous neurosyphilis (Z = 2.023, P = 0.044) in terms of CSF protein content. Electroencephalogram (EEG) results were abnormal in six patients, and imaging studies unveiled diverse findings in 46 patients. CONCLUSION: The study highlights the importance of neurological and/or ocular symptoms in diagnosing symptomatic neurosyphilis. Individuals with hypomnesia should be closely monitored for potential neurosyphilis. Integrating clinical manifestations, laboratory tests, EEG, and imaging can reduce misdiagnosis. This comprehensive approach shows promise in improving early identification and management of neurosyphilis.

Epstein-Barr virus-positive monoclonal lymphoplasmacytic proliferation associated with neurosyphilis in an immunocompetent patient: A case report.

Syphilis is an infectious disease caused by the spirochete bacterium Treponema pallidum. Neurosyphilis results from the infection of the nervous system with Treponema pallidum, which can occur at any stage of syphilis. Neurosyphilis is often overlooked because of its rarity. Early-stage neurosyphilis with brain mass formation is rare. We present a case of early-stage neurosyphilis with prominent Epstein-Barr virus (EBV)-positive monoclonal lymphoplasmacytic proliferation in an immunocompetent patient. A 36-year-old man presented with a chief complaint of a progressively worsening headache, a newly developed skin rash, and a fever. Magnetic resonance imaging showed a mass lesion, which measured 18 mm in diameter, in the left frontal lobe of the cerebrum. The patient underwent an emergency operation to remove the abscess. A pathological investigation revealed complex findings. There was an abscess in the cerebrum. Lymphoplasmacytic meningitis was also noted. In addition, a vaguely nodular lesion, which was composed of plasmacytoid and lymphoid cells, was observed around the abscess. Immunohistochemically, an anti-Treponema pallidum antibody revealed numerous Treponemas around the abscess. In situ hybridization revealed that the plasmacytoid and lymphoid cells were Epstein-Barr encoding region (EBER)-positive; κ-positive cells were significantly more prevalent than λ-positive cells, suggesting light-chain restriction. Postoperatively, parenteral antibiotics were administered for four weeks. The patient has been free of recurrence for two years since the surgery. No association between neurosyphilis and EBV-positive lymphoplasmacytic proliferation has ever been reported. Mass formation in early-stage neurosyphilis is an exceptionally rare event. The present case indicates that in syphilis patients, lymphoproliferative disorders that lead to mass formation may be caused by concomitant EBV reactivation. Furthermore, when treating patients with mass lesions of the central nervous system, it is important to check their medical history and perform laboratory screening for infectious diseases to avoid overlooking syphilis infections.

Serum Ubiquitin C-Terminal Hydrolase-L1, Glial Fibrillary Acidic Protein, and Neurofilament Light Chain Are Good Entry Points and Biomarker Candidates for Neurosyphilis Diagnosis Among Patients Without Human Immunodeficiency Virus to Avoid Lumbar Puncture.

BACKGROUND: Laboratory tests to diagnose neurosyphilis using cerebrospinal fluid (CSF) are currently disadvantageous as a lumbar puncture is required, which may result in patients with neurosyphilis missing an opportunity for early diagnosis. Thus, blood biomarker candidates that are more convenient and minimally invasive to collect for diagnosing neurosyphilis is urgently needed. METHODS: This observational study aimed to analyze serum ubiquitin C-terminal hydrolase-L1 (UCH-L1), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NF-L) levels in 153 patients without human immunodeficiency virus (HIV) and to evaluate their diagnostic performance in neurosyphilis compared with CSF. RESULTS: Serum UCH-L1, GFAP, and NF-L levels were significantly higher in patients with neurosyphilis compared with patients with uncomplicated syphilis or non-syphilis. For the diagnosis of neurosyphilis, serum UCH-L1, GFAP, and NF-L revealed sensitivities of 90.20%, 80.40%, and 88.24%, and specificities of 92.16%, 78.43%, and 80.39%, respectively, at cutoff levels of 814.50 pg/mL, 442.70 pg/mL, and 45.19 pg/mL, respectively. In patients with syphilis, serum UCH-L1, GFAP, and NF-L levels correlated strongly or moderately with those in the CSF, with similar or better diagnostic performance than those in the CSF. The testing algorithms' sensitivity and specificity increased to 98.04% and 96.08%, respectively, when subjected to parallel and combination testing, respectively. CONCLUSIONS: To avoid lumbar puncture, each serum UCH-L1, GFAP, and NF-L is a good entry point and biomarker candidate for the diagnosis of neurosyphilis among patients without HIV. These proteins used in concerto can further improve the diagnostic sensitivity and specificity.

The Utility of Biomarkers in the Clinical Management of Syphilis: A Systematic Review.

BACKGROUND: Routinely available laboratory tests for Treponema pallidum remain suboptimal for diagnostic, prognostic, predictive, and monitoring purposes. Biomarkers with enhanced performance characteristics can improve diagnostic confidence and facilitate management. We conducted a systematic review to examine the utility of biomarkers in the diagnosis and management of syphilis. METHODS: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses to identify articles for inclusion and independently reviewed them for eligibility and study quality using a 3-stage procedure. The search, conducted by a senior library informationist, used PubMed, Embase, Cochrane Library, and Scopus and included any study published before May 2022. RESULTS: Of the 111 studies identified, 31 (27.9%) were included in our review. Most studies were cross-sectional or prospective. The data were strikingly heterogeneous examining a variety of biomarkers across different syphilis stages, using different methodologies and definitions of treatment success. Available publications chiefly focused on diagnosing various syphilis stages, neurosyphilis and congenital syphilis, serological cure, the serofast state, and reinfection. CONCLUSIONS: Despite increasing attempts to identify novel biomarkers, we found limited evidence to support the use of any biomarker in clinical decision making at this time; the syphilis biomarker literature is heterogenous and lacks measurement of clinically meaningful end points. We recommend the formation of a working group to set priorities for syphilis biomarker research and to guide future study of clinically meaningful biomarkers.

A Cluster of Ocular Syphilis Cases with a Common Sex Partner - Southwest Michigan, 2022.

Untreated syphilis can lead to ocular syphilis, otosyphilis, and neurosyphilis, conditions resulting from Treponema pallidum infection of the eye, inner ear, or central nervous system. During March-July 2022, Michigan public health officials identified a cluster of ocular syphilis cases. The public health response included case investigation, partner notification, dissemination of health alerts, patient referral to a public health clinic for diagnosis and treatment, hospital care coordination, and specimen collection for T. pallidum molecular typing. Five cases occurred among southwest Michigan women, all of whom had the same male sex partner. The women were aged 40-60 years, HIV-negative, and identified as non-Hispanic White race; the disease was staged as early syphilis, and all patients were hospitalized and treated with intravenous penicillin. The common male sex partner was determined to have early latent syphilis and never developed ocular syphilis. No additional transmission was identified after the common male partner's treatment. Due to lack of genetic material in limited specimens, syphilis molecular typing was not possible. A common heterosexual partner in an ocular syphilis cluster has not been previously documented and suggests that an unidentified strain of T. pallidum might have been associated with increased risk for systemic manifestations of syphilis. A high index of clinical suspicion and thorough sexual history are critical to diagnosing ocular syphilis, otosyphilis, and neurosyphilis. Coordination of disease surveillance with disease intervention specialist investigation and treatment referral can interrupt syphilis transmission.

Neurosyphilis presenting with Guillain-Barre syndrome: a case report.

BACKGROUND: Syphilis is associated with a wide variety of systemic presentations, earning it the moniker "The great mimicker". Neurosyphilis is classically associated with meningovasculitis in the acute-subacute stage and tabes dorsalis and dementia paralytica in later stages. However, one of the less well described presentations include Guillain-Barre Syndrome. This case presents a patient with an ascending polyneuropathy suspicious for Guillain-Barre Syndrome who also had other atypical findings including a truncal sensory loss, optic disc swelling, and rash ultimately found to have neurosyphilis. Electrodiagnostic testing was consistent with demyelination, supporting a diagnosis of neurosyphilis associated Guillain-Barre Syndrome. CASE PRESENTATION: A 37-year-old female presented to the emergency department with a weakness and difficulty swallowing. She described a three-month history of symptoms, initially starting with a persistent headache followed by one month of a pruritic rash on her chest, palms, and soles. Two weeks prior to presentation, she developed progressive weakness in her arms, numbness in her arms and chest, and difficulty swallowing. Neurological exam was notable for multiple cranial neuropathies, distal predominant weakness in all extremities, length-dependent sensory loss, and hyporeflexia. Investigation revealed a positive Venereal Disease Research Laboratory in her cerebrospinal fluid without significant pleocytosis, contrast enhancement in cranial nerves V, VII, and VIII on MRI, and a demyelinating polyneuropathy on electrodiagnostic testing. She was diagnosed with Guillain-Barre syndrome, secondary to neurosyphilis. The patient acutely declined and required intubation, and ultimately made a full recovery after treatment with plasmapheresis and penicillin. CONCLUSIONS: This case describes a clinical entity of syphilitic Guillain-Barre Syndrome and highlights the importance of including syphilis in the differential of any patient presenting with ascending polyradiculopathy, especially given the resurgence of syphilis.

Neurosyphilis in the Northern Territory of Australia: a clinical guideline.

BACKGROUND: The Northern Territory (NT) of Australia is currently experiencing a syphilis epidemic. Neurosyphilis is commonly considered in the differential diagnosis for patients presenting with neurologic conditions such as dementia and stroke in the NT. AIMS: To explore the local epidemiologic, diagnostic and treatment complexities of neurosyphilis in the NT and produce a guideline for clinical practice. METHODS: A database search was undertaken and local and global neurosyphilis guidelines were analysed. A guideline was created based on findings of the critical review and consultation with local multidisciplinary experts. RESULTS: Neurosyphilis is frequently encountered in the NT but studies suggest it is often undertreated. Dementia is the most common clinical presentation locally. Establishing a diagnosis of neurosyphilis is complex and requires stepwise evaluation of clinical, laboratory and radiological findings. CONCLUSIONS: A clinical guideline and algorithm have been developed for the diagnosis and management of patients with neurosyphilis.

Comparison of molecular and serological assays on cerebrospinal fluid for the diagnosis of neurosyphilis.

BACKGROUND: Many assays are available on cerebrospinal fluid (CSF) for the diagnosis of neurosyphilis (NS) but there is no 'gold standard'. OBJECTIVES: The aim of this study was to evaluate different molecular and serological assays used in NS. METHODS: We evaluated two PCR assays and three serological techniques in parallel on CSF samples collected between 2019 and 2020 from patients suspected of NS. RESULTS: The study included 143 patients comprising 30 early NS, 7 late NS and 106 patients without a diagnosis of NS. All patients with NS were symptomatic and had either neurological (67.6%) or ophthalmological signs (54.1%). The qPCR and nPCR assays had overall sensitivities (Se) of 41% and 27%, respectively; with each an overall specificity (Sp) of 100%. VDRL had a Se of 51% and a Sp of 92%. Immunoblot had a Se of 62% and a Sp of 85%. Finally, treponemal tests (TT) had a Se of 96% and a Sp of 69%. CONCLUSIONS: Our study confirms the excellent specificity of molecular techniques allowing to avoid overdiagnosis of NS, and thus, unjustified intensive antibiotic therapy protocols. CSF TT, although not very specific, has an excellent Se confirming that there is almost never NS with negative CSF TT. VDRL and immunoblot tests have better overall diagnostic performance. However, none of these techniques has sufficient diagnostic performance to represent a 'gold standard'. Thus, the diagnosis of NS relies on a combination of clinical and biological parameters with the association of PCR with serology, associating VDRL and immunoblot, in CSF.

Neurosyphilis in a young man having HIV infection, blurring of vision and skin rash.

We report a 22-year-old homosexual man, a known case of HIV-1 infection but non-compliant to medications, who presented with a 5-month history of progressive painless non-pruritic coin-shaped skin lesions and recent gradual bilateral blurring of vision. His history divulged a primary syphilitic event 1 year prior to the present clinical manifestations. Investigation led to the diagnosis of neurosyphilis with ocular involvement with concurrent signs of secondary syphilis. Treatment with aqueous crystalline penicillin G, ophthalmic steroid and tropicamide drops, and topical emollients resulted in significant clinical improvement of ocular symptoms and skin lesions. The diagnosis of neurosyphilis requires a high degree of clinical suspicion and should be included in the differential diagnosis of unexplained ocular symptoms, particularly in men who have sex with men and HIV-infected patients. This is necessary for the early diagnosis, appropriate management, and good outcome of these patients.

Imaging features of neurosyphilis.

Syphilis is an infectious disease caused by the spirochete Treponema pallidum, subspecies pallidum. Although its incidence has declined after the widespread availability of penicillin, it has recently re-emerged, especially in men who have sex with men and in people living with human immunodeficiency virus (HIV). The neurological manifestations of syphilis, generally known as neurosyphilis, may appear at any time during the infection, including the initial years after the primary infection. Neurosyphilis can be asymptomatic, only with cerebrospinal fluid abnormalities, or symptomatic, characterized by several different clinical syndromes, such as meningitis, gumma, meningovascular, brain parenchyma involvement, meningomyelitis, tabes dorsalis, and peripheral nervous system involvement. However, these syndromes may simulate several other diseases, making the diagnosis often a challenge. In addition, syphilis can also be vertically transmitted from mother to child during pregnancy, leading to neurological manifestations. Neuroimaging is essential to demonstrate abnormal brain or spinal cord findings in patients with neurosyphilis, aiding in the diagnosis, treatment, and follow-up of these patients. This article aims to review the imaging features of neurosyphilis, including the early and late stages of the infection.

[Neurosyphilis or not - a case of a differential diagnostic challenge]. / Neurosyphilis vagy nem ­ egy differenciáldiagnosztikai kihívás esete.

We report the case of a 42-year-old woman with paraparesis associated with transverse myelitis. For differential diagnostics detailed microbiological, cerebrospinal fluid (CSF) and neuroimaging examinations were performed. Syphilis was confirmed, but diagnosis of neurosyphilis was only probable based on the CSF microbiological test results. The beneficial treatment response to application of the therapeutic protocol for syphilis supported the supposed diagnosis of syphilis-associated myelitis in our case. In this case report we reviewed the differential diagnostic tools of myelopathies/myelitis.
Nowadays regarding to growing prevalence of syphilis worldwide physicians should face on its presence and medical consequences.

Previous Syphilis Alters the Course of Subsequent Episodes of Syphilis.

BACKGROUND: The influence of previous syphilis on the course of a subsequent episode is unknown. METHODS: Individuals enrolled in a study of cerebrospinal fluid (CSF) abnormalities in syphilis were allowed to enroll in the study again with subsequent syphilis. For each participant, the index episode was defined as the most recent syphilis episode for which the study entry visit was performed within 30 days of the syphilis diagnosis date. Venipuncture and lumbar puncture (LP) were performed. Total number of syphilis episodes was determined by review of medical and public health records. T. pallidum DNA in blood and rRNA in CSF were detected by polymerase chain reaction (PCR) and reverse transcriptase PCR. Odds ratios (ORs) with 95% confidence intervals (95% CI) were determined by logistic regression. RESULTS: 651 individuals had one (n = 482), two (n = 121) or three or more (n = 48) episodes of syphilis. The proportion of individuals whose index episode was early latent stage was significantly higher in those with ≥3 syphilis episodes; this relationship was reduced to a trend when rate of testing was taken into account. Adjusted odds (aOR) of detection of T. pallidum DNA in blood or rRNA in CSF at the index episode were significantly lower in those with previous syphilis (0.17 [95% CI, 0.09-0.31] and 0.15 [95% CI, 0.07-0.35]). The aOR for neurosyphilis at the index episode was also significantly lower in individuals with previous syphilis (0.54 [95% CI, 0.34-0.87]). CONCLUSIONS: Previous syphilis attenuates the manifestations of subsequent infection with T. pallidum.

Management of Adult Syphilis: Key Questions to Inform the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infections Treatment Guidelines.

A panel of experts generated 5 "key questions" in the management of adult syphilis. A systematic literature review was conducted and tables of evidence were constructed to answer these questions. Available data suggest no clinical benefit to >1 dose of benzathine penicillin G for early syphilis in human immunodeficiency virus (HIV)-infected patients. While penicillin remains the drug of choice to treat syphilis, doxycycline to treat early and late latent syphilis is an acceptable alternate option if penicillin cannot be used. There are very limited data regarding the impact of additional antibiotic doses on serologic responses in serofast patients and no data on the impact of additional antibiotic courses on long-term clinical outcomes. In patients with isolated ocular or otic signs and symptoms, reactive syphilis serologic results, and confirmed ocular/otic abnormalities at examination, a diagnostic cerebrospinal fluid (CSF) examination is not necessary, because up to 40% and 90% of patients, respectively, would have no CSF abnormalities. Based on the results of 2 studies, repeated CSF examinations are not necessary for HIV-uninfected patients or HIV-infected patients on antiretroviral therapy who exhibit appropriate serologic and clinical responses after treatment for neurosyphilis. Finally, several important gaps were identified and should be a priority for future research.

Clinical outcomes of HIV-syphilis coinfection among patients with no neurological symptoms: a retrospective cohort study.

OBJECTIVE: Our objective was to describe and compare the occurrence of neurological outcomes and neurosyphilis in people living with HIV with incident syphilis and no neurological symptoms who underwent early screening for asymptomatic neurosyphilis (ANS) or regular clinical management without a lumbar puncture. METHODS: This was a retrospective cohort study in a single referral centre of Sao Paulo, Brazil. Patients with incident syphilis diagnosed between January 2000 and August 2016 and meeting the adapted criteria for ANS investigation suggested by Marra et al. (CD4+ T-cell counts ≤350 cells/mm³ and/or venereal disease research laboratory test results ≥1:16) were identified. Those with no neurological symptoms and immediately referred for lumbar puncture were categorized as group 1, and those not referred for cerebrospinal fluid collection were categorized as group 2. We compared the occurrence of neurological symptoms and neurosyphilis diagnoses between the groups using incidence rates and Kaplan-Meier curves. RESULTS: We included 425 participants with a median follow-up of 6 years. The incidence rate of neurological symptoms was 36.5/1000 person-years in group 1 and 40.6/1000 person-years in group 2 (incidence rate ratio [IRR] 0.90; 95% confidence interval [CI] 0.57-1.39; p = 0.62). The incidence rate of neurosyphilis was 15.0 cases/1000 person-years in group 1 and 6.7 cases/1000 person-years in group 2 (IRR 2.26; 95% CI 0.93-5.68; p = 0.05). CONCLUSIONS: We found no statistically significant differences between groups in the incidence rates of neurological symptoms and neurosyphilis. Our findings support the current guidelines, which suggest a less invasive approach regarding ANS investigation among people living with HIV with incident syphilis.

Reported Neurologic, Ocular, and Otic Manifestations Among Syphilis Cases-16 States, 2019.

BACKGROUND: Syphilis can cause neurologic, ocular, or otic manifestations, possibly resulting in permanent disability or death. In 2018, the Centers for Disease Control and Prevention began collecting syphilis clinical manifestation data via the National Notifiable Diseases Surveillance System. We present the first reported US syphilis neurologic, ocular, and otic manifestation prevalence estimates. METHODS: We reviewed 2019 National Notifiable Diseases Surveillance System data to identify jurisdictions reporting 70% or greater of syphilis cases 15 years or older with clinical manifestation data (considered "complete reporting"). Among these jurisdictions, we determined reported neurologic, ocular, and otic manifestation prevalence, stratified by demographic, behavioral, and clinical characteristics. RESULTS: Among 41,187 syphilis cases in 16 jurisdictions with complete reporting, clinical manifestations were infrequently reported overall: neurologic (n = 445, 1.1%), ocular (n = 461, 1.1%), otic (n = 166, 0.4%), any (n = 807, 2.0%). Reported clinical manifestation prevalence was highest among cases 65 years or older (neurologic, 5.1%; ocular, 3.5%; otic, 1.2%) and those reporting injection drug use (neurologic: 2.8%; ocular: 3.4%; otic: 1.6%). Although reported neurologic and ocular manifestation prevalence was slightly higher among human immunodeficiency virus (HIV)-infected versus HIV-negative persons, approximately 40% of cases with manifestations were HIV-negative. Reported otic manifestation prevalence was similar regardless of HIV status. When stratifying by HIV status and syphilis stage, reported prevalence was highest among HIV-infected persons with unknown duration/late syphilis (neurologic, 3.0%; ocular, 2.3%; otic, 0.7%). CONCLUSIONS: Reported neurologic, ocular, and otic manifestation prevalence was low among syphilis cases, but these data are likely an underestimate given potential underreporting. Reported clinical manifestation frequency, including among HIV-negative persons, emphasizes the importance of evaluating all syphilis cases for signs/symptoms of neurosyphilis, ocular syphilis, and otosyphilis.

Clinical and laboratory features in patients with positive syphilis serology presenting with acute ischemic stroke or transient ischemic attack: a prospective cohort study.

BACKGROUND: Neurosyphilis (NS) can lead to acute ischemic stroke (AIS) or transient ischemic attack (TIA). We compared the clinical characteristics and laboratory features among AIS and TIA patients who were syphilis-seronegative (control group) or had latent syphilis (LS) or NS to evaluate their stroke outcome. METHODS: This prospective cohort study was conducted on patients who had recently suffered AIS or TIA. After serological syphilis screening, clinical and laboratory data were collected, and brain imaging and spinal tap (serologically syphilis-positive patients only) were performed. Stroke outcome was re-evaluated approximately three months later. RESULTS: The 344 enrolled patients were divided into three groups: control group (83.7%), LS (13.1%), and NS (3.2%). A multivariate analysis revealed: 1) age of ≥ 70 years, generalized brain atrophy via imaging, and alopecia (adjusted odds ratio [AOR] = 2.635, 2.415, and 13.264, respectively) were significantly associated with LS vs controls; 2) age of ≥ 70 years (AOR = 14.633) was significantly associated with NS vs controls; and 3) the proportion of patients with dysarthria was significantly lower (AOR = 0.154) in the NS group than in the LS group. Regarding the NS patient cerebrospinal fluid (CSF) profile, only 2/11 cases had positive CSF-Venereal Disease Research Laboratory (VDRL) test results; the other nine cases were diagnosed from elevated white blood cell counts or protein levels combined with positive CSF fluorescent treponemal antibody absorption (FTA-ABS) test results. Regarding disability, the initial modified Rankin scale (mRS) score was lower in the control group than in the NS group (p = 0.022). At 3 months post-stroke, the mRS score had significantly decreased in the control (p < 0.001) and LS (p = 0.001) groups. Regarding activities of daily living, the 3-month Barthel Index (BI) score was significantly higher in control patients than in LS (p = 0.030) or NS (p = 0.002) patients. Additionally, the 3-month BI score was significantly increased in the control (p < 0.001) and LS (p = 0.001) groups. CONCLUSIONS: Because syphilis was detected in many AIS and TIA patients, especially those aged ≥ 70 years, routine serological syphilis screening may be warranted in this population. Patients with syphilitic infection had worse stroke outcomes compared with NS patients.

An unusual case of tertiary syphilis.

We report a rare case of tertiary syphilis in a middle aged man who presented with a 6-month history of ulceration of his left eye with extreme pain. Physical examination revealed fistulas, granuloma with ulcer, and corneal opacity with granulomatous conjunctivitis in the left eye. Based on the patient's clinical manifestations and auxiliary examination results, neurosyphilis was diagnosed.