Introduction
Syphilis is a sexually transmitted infection caused by Treponema pallidum, known for the diagnostic challenges it presents due to its varied clinical manifestations, earning it the nickname the “great imitator.” This multifaceted disease has seen a troubling resurgence as a significant public health issue over recent decades, particularly affecting men who have sex with men (MSM) and people living with HIV (PLWH). Notably, syphilis can progress to a more severe form known as neurosyphilis at any stage following the initial infection. Although the incidence of neurosyphilis had dramatically decreased with the introduction of antibiotics, recent years have seen an alarming rise in the number of reported cases. Research indicates that PLWH are at an increased risk, being approximately twice as likely to develop neurosyphilis compared to their immunocompetent counterparts.
In recent years, there’s been a notable increase in patients seeking emergency care due to complications from syphilis. Nonetheless, there is a significant gap in systematic reviews of these cases to understand their manifestations better. This study set out to compile and analyze the profiles of patients who presented with neuropsychiatric symptoms in the emergency department, eventually diagnosed with neurosyphilis. A holistic analysis was undertaken, evaluating their demographic details, clinical symptoms, laboratory results, and radiographic findings, alongside assessing their responses to treatments. By documenting these profiles, the study aims to enhance clinical awareness and promote early diagnosis of neurosyphilis among emergency department physicians.
Materials and Methods
Study Subject
Table 1 Diagnostic Criteria for Neurosyphilis Patients Included in the Study
Study Methods
For the eligible subjects, comprehensive data were meticulously collected, including demographics, medical and sexual histories, clinical symptoms, disease progression, and previous treatments. The study involved extensive examinations, including physical evaluations, cognitive functioning tests, CSF laboratory analyses, and cranial MRI scans. An experienced neurologist (C. Mao) and a skilled radiologist (M. Li) were responsible for interpreting the MRI findings to provide definitive results. Treatment strategies were documented, alongside subsequent evaluations of serum RPR levels. Treatment response for neurosyphilis was judged based on several key criteria: a notable decrease (greater than fourfold reduction or complete negativity) in serum RPR titers within one year following discharge, or the normalization of CSF—with a necessary reduction in white blood cell (WBC) counts and normalization of protein levels—three months post-treatment. Furthermore, any improvement in clinical symptoms, as reported by both physicians and patients, was factored into the evaluation of treatment success, especially when lumbar puncture assessments were not performed post-treatment.
Patient Informed Consent
The study committee affirmed that since this investigation was retrospective and all patient identities were anonymized, obtaining written informed consent from participants was deemed unnecessary.
Results
Personal Profile and Baseline Characteristics
Upon reviewing medical records, a total of 12 neurosyphilis cases were ultimately identified. Among these cases, the gender distribution revealed nine males and three females. The patients’ ages ranged significantly from 30 to 67 years, with an average age of 52.3 years and a median age of 52.5 years. Intriguingly, only one patient acknowledged a previous syphilis infection during the inquiry. When probing for potential infection sources, only three participants admitted to engaging in high-risk sexual behavior. Among these three, two males disclosed sexual encounters with sex workers, while one female linked her infection to her husband’s involvement with a sex worker. A minor fraction (16.7%) of patients reported past drug usage, while a substantial 75.0% denied any suspicious personal histories. The patients encompassed various occupational backgrounds, with 41.7% employed as clerks, 25.0% as factory workers, 25.0% classified as unemployed, and 8.3% engaged in artistic professions. Furthermore, analysis of co-infection with other infectious diseases revealed that only one patient (8.3%) was co-infected with HIV, cytomegalovirus (CMV), and Epstein-Barr virus (EBV), while two patients were also noted for having hepatitis B virus (HBV) infections (16.7%).
Clinical Manifestations and Disease Course
As depicted in Table 2, the initial and most frequently encountered manifestation in the inpatient neurosyphilis cohort was a notable decline in memory function, reported in eight cases (66.7%). Moreover, several other primary symptoms surfaced within the study group, including dyskinesia (n = 2), dysesthesia (n = 1), and epilepsy (n = 1). Patients generally sought emergency neurological intervention as their symptoms worsened, with four individuals experiencing abnormal behaviors tied to acute hallucinations, while three presented with grand mal seizures. Additionally, three patients exhibited exacerbated cognitive decline, characterized by nonsensical responses, and mobility impairments were reported in two patients.
Physical Examination and Assessment of Cognitive Condition
Pathological reflexes were appropriately assessed, showing presence in four neurosyphilis patients (33.3%) of this cohort—three patients exhibited positive Babinski’s signs, alongside other positive findings for Gordon, Oppenheim, Chaddock signs, and the palmomental reflex. Furthermore, Argyll Robertson’s pupil was noted in three patients. In cognitive assessments, one individual recorded a Montreal Cognitive Assessment (MoCA) score of 22 alongside a Mini-Mental State Examination (MMSE) score of 24. The remaining scores were also provided, with two patients holding MMSE scores of 23 and 8. It is significant to note, however, that comprehensive cognitive assessments were lacking for the other patients.
Laboratory Tests
Every included subject underwent thorough serum RPR and TPPA testing upon admission, with all results in TPPA testing returning positive for Treponema pallidum. With regard to RPR serum tests, only one case yielded a negative result, while all other patients presented positive results. The titers correlating with positive RPR cases ranged from 1:32 to 1:256, with a median titer of 1:32. In addition, CSF analyses uncovered varied CSF RPR titers, ranging from negative to a maximum of 1:128 positive, with levels equal to or greater than 1:8 observed in four patients (33.3%). The TPPA tests for CSF samples across all patients also presented reactivity, affirming the presence of Treponema pallidum. Leukocyte counts among patients diagnosed with general paresis spanned from 2 to 66×106 cells per liter, with seven patients exhibiting CSF leukocyte counts exceeding 5×106 cells per liter. Notably, CSF protein levels fluctuated from 470.0 to 1050.0 mg, with an average protein concentration of 766.7 mg, all of which surpassed the standard thresholds for normal CSF protein levels.
Cranial MRI
Out of the 12 patients included in the study, cranial MRI scans were conducted on 11 individuals. Figure 1 demonstrated typical lesions at the medial temporal lobes bilaterally in patients diagnosed with neurosyphilis. Among those examined, three patients (27.3%) demonstrated no discernible cerebral abnormalities during the MRI evaluations. The most frequently affected structures included the ventricular and paraventricular areas (n = 4) as well as the temporal lobes (n = 4), while two patients showed involvement of the hippocampus, frontal lobe, cerebellum, and brainstem. Additionally, patchy or speckled hyperintensities were identified in seven patients. Common findings revealed cerebral atrophy (n = 3) and dilated ventricles and fissures (n = 2). Cerebral atrophy was documented in diverse locations, including the cerebellum and brainstem (n = 1), bilateral hippocampus (n = 1), and the temporal lobes bilaterally (n = 1).
Treatment and Response
A penicillin-based anti-syphilitic regimen was administered to 11 out of the 12 patients. Four of them received treatment in accordance with both the U.S. CDC guidelines and the Chinese sexually transmitted infection protocols for managing syphilis. This treatment protocol involved intravenous administration of aqueous crystalline penicillin at a dosage of 3–4 million units every four hours for a duration of 10 to 14 days; if deemed necessary, this was followed by intramuscular benzathine penicillin at a dosage of 2.4 million units weekly for three additional weeks. To mitigate the Jarisch-Herxheimer reaction, corticosteroids were concurrently prescribed to two patients. Remarkably, one patient did experience this reaction after receiving the penicillin-based intervention without corticosteroid support. Post-treatment evaluations of serum tests were accessible for eight patients, revealing RPR titers ranging from 1:1 to 1:128. The median post-treatment titer was recorded at 1:8, a significant decrease from the pre-treatment median of 1:32. Alarmingly, the RPR titer failed to drop in four patients (33.3%), two of whom had received adequate penicillin treatment, while the other two reported inconsistent compliance and non-adherence to the treatment regimen.
Discussion
The data collected from emergency neurosyphilis patients referred to a tertiary medical center in Beijing, China, sheds important light on the characteristics and challenges of diagnosing and treating neurosyphilis in an emergency setting. This detailed analysis outlines the typical patient profile, emphasizing the pressing need for improved management in emergency departments. Currently, there remains a paucity of systematic analyses concerning patient cohorts diagnosed with neurosyphilis in emergent situations. This study could serve as a critical reference for both dermatologists and neurologists involved in the diagnosis of neurosyphilis.
The predominant demographic seeking medical assistance for acute symptoms of neurosyphilis appeared to be middle-aged males, which aligns with contemporary estimates of who is most affected by this re-emerging infection. Interestingly, only one individual reported a past syphilitic infection alongside noticeable genital rash. A striking 75% of participants denied any prior histories deemed suspicious for syphilis infection. Previous investigations have highlighted a significant degree of concealment regarding STI-related sexual behaviors among patients in China. Specifically, when the clinical symptoms primarily present as neuropsychiatric rather than genital lesions, this concealment increases the risk of misdiagnosis and underdiagnosis. Thus, even in the absence of clearly documented personal histories or risk factors, healthcare providers should remain vigilant about the possibility of neurosyphilis in middle-aged males presenting with neuropsychiatric complaints in emergency situations.
A key aspect of clinical examinations in suspected neurosyphilis cases is the identification of Argyll Robertson’s pupil, which previous studies have indicated appears in over 20% of patients with general paresis of the insane; this cohort reflects a similar positivity rate of approximately 25%. Noteworthy abnormalities, including a positive Babinski sign and palmomental reflex, were also present in this patient group. Given the substantial spinal cord involvement typically associated with neurosyphilis, the presenting neurological symptoms can vary widely and may lack pathognomonic features. Furthermore, while MMSE and MoCA scores offer valuable insights into cognitive function and clinical significance, they remain underutilized in real-time assessments within emergency scenarios. Research has previously reported average MMSE scores around 17.8 for neurosyphilis patients, which may point toward moderate levels of dementia among this cohort. Continuous assessment of MMSE and MoCA scores during the treatment period serves to track cognitive functionality, providing critical data for making necessary treatment alterations based on variations observed in scores.
A definitive diagnosis of neurosyphilis predominantly hinges upon serological tests and CSF laboratory analysis. In our examined cohort, only four cases (33.3%) showcased CSF RPR titers exceeding or equal to 1:8. Previous literature has also highlighted concerningly high false-negative rates in the context of CSF RPR testing among neurosyphilis patients. These results underscore the challenges in accurately diagnosing neurosyphilis when antibody levels in both blood and cerebrospinal fluid may be low or undetectable as a consequence of prolonged infection duration. Moreover, the confounding prozone effect within the RPR assay partially elucidates the phenomenon of elevated false-negative results; this phenomenon occurs when exceedingly high antibody concentrations lead to falsely diminished or negative responses in serological evaluations.
A substantial 33.3% of individuals within our cohort received standardized treatment in alignment with established guidelines. However, the observed cure rate remained concerningly low, often accompanied by irreversible neurological damage and persistently positive RPR titers. The utilization of standardized treatment protocols in emergency settings is alarmingly infrequent, particularly in situations lacking dermatological guidance, reinforcing the need for improved dermatological intervention in emergency clinical contexts.
Conclusion
In conclusion, this study illuminates the multifaceted challenges surrounding the diagnosis and management of neurosyphilis within emergency department patients, particularly those middle-aged males who present with acute neuropsychiatric symptoms. The pattern of delayed diagnosis remains prevalent, often leading to irreversible neurological complications. This research underscores the crucial importance of incorporating neurosyphilis into differential diagnoses for patients demonstrating neuropsychiatric symptoms, even in cases where prior medical histories fail to suggest potential risk factors. Accurate clinical manifestations, alongside comprehensive laboratory evaluations and neuroimaging findings, are vital elements in the process of diagnosing and managing neurosyphilis within emergency department frameworks.
Syphilis: The Great Imitator Revisited
Welcome, dear readers! Today, we’re diving into the murky depths of syphilis—an infection that’s rebranded itself as “the great imitator.” Not to be outdone by your average flu, this little spirochete, Treponema pallidum, has all the charm of a chameleon at a tie-dye convention, blending in and mimicking all sorts of medical conditions. It’s enough to make any emergency department doctor tear their hair out!
The Dramatic Comeback of Syphilis
Let’s be honest: syphilis is having a moment. After decades of pretending to be gone, it’s popping back up like a bad penny. And its recent rise is particularly noticeable among men who have sex with men and those living with HIV. (Surprise! This isn’t just a disease for the unloved and forgotten.) This particular infection doesn’t just stay put; it can sneakily progress to neurosyphilis at any time—much like a bad sitcom that refuses to be canceled.
What’s the Deal with Neurosyphilis?
For the uninitiated, neurosyphilis is not your average tête-à-tête with an STI. It’s an aggressive, sometimes terrifying manifestation where the syphilis bacteria decide your central nervous system deserves a little drama. The prevalence of neurosyphilis may have dipped thanks to antibiotics, but don’t be fooled—recent years have seen a spike in reported cases. And guess who’s most at risk? Those living with HIV—twice as likely to develop this neurological nightmare than those with a healthy immune system. Now, imagine trying to explain that at a dinner party! “So, how’s your immune system treating you?” “Well, it might be hosting a wild syphilis party in my brain!”
Patient Profiles: A Mixed Bag
Now, let’s pull back the curtain on the study that surveyed a dozen individuals diagnosed with neurosyphilis after a trip to the emergency department. Spoiler alert: the majority were male. The age range? A ripe middle age, from 30 to 67 years old. Only one of the patients admitted to a history of syphilis—classic! The rest? Well, let’s just say their “suspicious personal histories” could fill a sitcom’s plotline. Only a third of them had anything resembling a thrilling backstory, including a brush with high-risk behaviors and, shall we say, the more colorful side of life.
Clinical Manifestations: The Symptoms that Steal the Show
So, what should you be on the lookout for if you suspect someone might have neurosyphilis? Spoiler alert: memory loss seems to take the spotlight, showing up in almost 67% of cases like an uninvited guest who refuses to leave. Other symptoms included the delightful ensemble of dystonia, dysesthesia, and even seizures—talk about a party no one wants to be invited to!
Diagnostic Challenges: Welcome to the Circus!
Now, don’t think it’s all straightforward. Oh no, diagnosing neurosyphilis is like finding Waldo in a field full of Waldos. Standard tests like the Rapid Plasma Reagin (RPR) and the Treponema pallidum particle agglutination assay (TPPA) often come back swinging, with unexpected results. Just when you think you’ve got the diagnosis nailed down, you remember the prozone effect where you might get a false-negative because the antibodies got a little too overwhelmed. It’s like hosting a party and realizing you forgot to send invites!
Imaging: A Peek Inside the Chaos
Cranial MRIs illustrated some of the complications resulting from this infection. The most commonly affected areas were temporal lobes and ventricular structures—think of them as the VIP rooms of your brain. But, surprisingly, a few patients showed no significant cerebral abnormalities. Just goes to show, neurosyphilis can be as unpredictable as a cat on a hot tin roof!
Treatment: Antibiotics to the Rescue?
When it comes to treatment, penicillin reigns as king. Yet, even with the best laid plans, results can be a bit underwhelming. Some patients simply didn’t respond or followed the treatment regimen like they followed their 2020 fitness goals—abysmally. Talk about a frustrating therapeutic intervention!
What Can We Learn?
In conclusion, dear healthcare warriors, we’ve learned that the great imitator is still out there, disguised and dashing through our defenses. Diagnosing and managing neurosyphilis remains a daunting task, especially when symptoms suddenly turn a patient into a walking enigma. As emergency clinicians, we need to keep our eyes peeled for this sneaky devil, remembering that not all heroes wear capes; sometimes, they wear scrubs and have a deep understanding of the history of STIs. And if you ever do encounter someone who seems to be having neurological issues, while the classic talk about “allergic to penicillin” might be intriguing, remember: you could be looking at neurosyphilis achieved through the great art of denial!
Stay vigilant, stay informed, and may you never face a category 5 syphilis storm without your life preservers! Until next time, keep those jokes in tow and your diagnostic skills honed!
