Neurosyphilis presenting as limbic encephalitis.

A man in his 50s presented with focal seizures and was found to have an inflammatory cerebrospinal fluid (CSF) with bilateral mesiotemporal lobe hyperintensity on magnetic resonance imaging (MRI) of the brain. Corticosteroid treatment was initiated for management of limbic encephalitis. Focal seizures, imaging abnormalities and inflammatory CSF persisted despite treatment and the patient was found to have neurosyphilis after developing neuropsychiatric symptoms. Syphilis is a sexually transmitted bacterial infection with multisystem involvement including neurological and psychiatric manifestations. Case reports have emerged of neurosyphilis presenting as limbic encephalitis with CSF pleocytosis and temporal lobe hyperintensity on MRI of the brain. Persistence of CSF or MRI abnormalities despite immunosuppressive therapy for limbic encephalitis should prompt investigation for alternate causes of chronic meningoencephalitis, which can occasionally include neurosyphilis.

[Syphilis: uncommon presentation forms]. / Sífilis: formas de presentación poco frecuentes.

Uncommon forms of syphilis exist, among which neurosyphilis, otosyphilis, and ocular syphilis are included. Neurosyphilis is the infection of the central nervous system caused by Treponema pallidum. The clinical manifestations of neurosyphilis are diverse and include early, late, and atypical forms. Syphilis can affect virtually any ocular structure and can occur at any stage of the disease, as well as otosyphilis. The diagnosis of these conditions is often challenging. However, it is important to consider them as a differential diagnosis, as most of these clinical manifestations are reversible with appropriate antibiotic treatment. A case series study of patients diagnosed with neurosyphilis, otosyphilis, and ocular syphilis, who were admitted to a tertiary-level hospital, is here presented: syphilitic meningitis with cranial nerve involvement, and seizures (case 1), ocular syphilis (case 2), general paresis (case 3), and tabes dorsalis (case 4). Half of the patients presented bilateral sensorineural hearing loss; and also half of the patients had reactive VDRL in cerebrospinal fluid. All were treated with aqueous penicillin G, and in two of these cases, ceftriaxone was chosen to complete ambulatory treatment. One patient had an unfavorable outcome and died (case 1); another was lost in follow-up (case 4); one completely resolved his symptoms (case 2); and another one experienced symptom relapse six months after treatment (case 3).

Existen formas de presentación poco frecuentes de sífilis, dentro de las cuales se incluyen la neurosífilis, otosífilis y sífilis ocular. La neurosífilis es la infección del sistema nervioso central por Treponema pallidum. Las manifestaciones clínicas de neurosífilis son variadas e incluyen formas tempranas, tardías y atípicas. Además, la sífilis puede comprometer prácticamente cualquier estructura ocular, en cualquier etapa de la enfermedad, como así también la otosífilis. El diagnóstico de estas entidades suele ser dificultoso. Sin embargo, resulta importante considerarlas como diagnósticos diferenciales, ya que la mayoría de estas manifestaciones son reversibles con tratamiento antibiótico adecuado. Se presenta una serie de casos de pacientes con diagnóstico de neurosífilis, otosífilis y sífilis ocular, que cursaron internación en un hospital de tercer nivel: meningitis sifilítica con compromiso de pares craneales y convulsiones (caso 1), sífilis ocular (caso 2), paresis general (caso 3) y tabes dorsalis (caso 4). La mitad de los pacientes presentó hipoacusia neurosensorial bilateral. El 50% presentó VDRL reactiva en líquido cefalorraquídeo. Todos fueron tratados con penicilina G sódica y en el 50% se optó por el uso de ceftriaxona como modalidad para finalizar el tratamiento en internación domiciliaria. Respecto a la evolución de los pacientes, uno de ellos falleció como consecuencia del cuadro de neurosífilis (caso 1), otro se perdió en el seguimiento (caso 4) mientras que, de los dos restantes, el caso 3 presentó recaída de su enfermedad a los 6 meses del tratamiento y el caso 2 resolvió ad integrum su sintomatología.

[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.

Neurosyphilis Mimicking Connective Tissue Disease.

A male in his 60s developed a pruritic, maculopapular rash on his torso and arms, sparing his palms and soles. He tested positive for ANA and an initial skin biopsy identified "bullous lupus," supporting the diagnosis of a connective tissue disease. Additional symptoms included headaches, facial nerve palsy and hearing loss, which partially responded to oral corticosteroids. He subsequently developed a steroid-dependent left eye scotoma, neuroretinitis and optic nerve papillitis. Mycophenolate mofetil was added but an attempted oral steroid taper led to a worsening rash, progressive retinitis and papillitis. Neurosyphilis was confirmed by serum positive rapid plasma reagin test, reactive treponema pallidum antibodies, positive cerebrospinal fluid venereal disease research laboratory and positive spirochete immunostain of skin biopsy of lesional (rash) tissue. Treatment with intravenous ceftriaxone resolved his rash and visual symptoms. It is important to consider syphilis as a mimicker of connective tissue diseases.

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.

A Rare Case of Blindness Caused by Syphilis with Malignant Hypertensive Nephropathy.

The number of patients with syphilis has been rapidly increasing. Without treatment, syphilis can damage various organs and become life-threatening. We herein report a 29-year-old woman diagnosed with neurosyphilis, acute hydrocephalus, syphilitic uveitis combined with hypertensive retinopathy, and malignant hypertensive nephropathy. To our knowledge, this is the first report of syphilis complicated with malignant hypertensive nephropathy proven by a renal biopsy. Neurosyphilis was successfully treated with intravenous penicillin G, and severe hypertension subsequently resolved. However, delayed medical examinations and complications of syphilitic uveitis and hypertensive retinopathy resulted in irreversible visual loss. To prevent irreversible organ damage, early treatment is essential.

[A case of neurosyphilis presenting as bilateral temporal, cortical and subcortical encephalitis].

A 37-year-old man who had a low grade fever for 5 days admitted to our hospital due to disturbance of consciousness and seizure. Brain MRI showed abnormal hyperintensity in the bilateral temporal lobes, cortical and subcortical lesions on fluid-attenuated inversion recovery image. Treponemal and non-treponemal specific antibodies were positive in serum and cerebrospinal fluid, therefore he was diagnosed as having neurosyphilis. Treatment with intravenous penicillin G and metylpredonisolone improved his clinical symptons, imaging abnormalities and CSF findings. Patients of neurosyphilis with mesiotemporal encephalitis show common features such as young age, HIV-negative, subacute cognitive impairment and seizure, as seen in our case. Early diagnosis of neurosyphilis and appropriate treatment make clinical improvement, however the clinical diagnosis of neurosyphilis is sometime difficult because most patients present with disturbance of consciousness or seizure. The possibility of neurosyphilis should be considered when MRI results indicate temporal abnormalities.

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.

A Failure of Rapid Drug Desensitization.

We present the case of a patient who was unable to tolerate rapid drug desensitization protocol to receive a continuous penicillin (PCN) G infusion for the treatment of neurosyphilis. A 38-year-old male with past medical history for human immunodeficiency virus, migraines, PCN allergy, doxycycline allergy, shellfish allergy, and untreated latent syphilis presented to the emergency room for a posterior migraine with associated nausea, vomiting, photophobia, right-sided paresthesias, and "shaky" vision. He was diagnosed with neurosyphilis and underwent rapid drug desensitization with the goal to receive a continuous infusion of PCN G. The patient's hospital course was complicated by intermittent drug reactions consisting of tachycardia, rash, and dyspnea, followed by periods of being able to tolerate the infusion. After being able to tolerate the recommended dose of PCN infusion, the patient was discharged home to complete the course. However, he returned almost immediately after a recurrence of symptoms at home requiring the use of intramuscular epinephrine. Ultimately, the patient was transitioned to ceftriaxone and completed the infusion course as an inpatient because of continued intermittent recurrence of drug reaction symptoms.

[A case of neurosyphilis presenting as sudden onset of limbic encephalitis].

A 52-year-old male was carried to hospital by ambulance, because of an abrupt abnormal behavior and impaired consciousness. Soon after the arrival, the patient started a generalized seizure. Although the seizure was stopped by Midazolam, amnesia were observed. With meningeal irritation signs, in addition to the clinical course, the patient was thought to develop limbic encephalitis. The cause of the encephalitis was diagnosed as neurosyphilis because of the positive serum and CSF syphilis reactions, and the patient was treated with penicillin G from the first admission day on. Steroid pulse therapy was also conducted, followed by acyclovir since herpes encephalitis could not be ruled out; the brain MRI showed left-side dominant T2/FLAIR high intensity lesions in the bilateral temporal lobes and left hippocampus. With the treatment progression, the amnestic syndrome improved and the patient returned to work. Although neurosyphilis is a rare cause of acute onset limbic encephalitis, it is important to keep the possibility of this disease in mind in making a treatment plan.

Ceftriaxone compared with penicillin G for the treatment of neurosyphilis: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Neurosyphilis may cause irreversible neurological sequelae. First-line treatment consists of penicillin G, with ceftriaxone being an alternative treatment in patients allergic to penicillin. The lack of clinical data comparing the efficacy of these two drugs indicated the need for comparative clinical trials to improve national treatment guidelines in China. METHODS/DESIGN: In this multicenter randomized controlled clinical trial, 290 patients newly diagnosed with neurosyphilis will be randomized 1:1 to treatment with aqueous crystalline penicillin G (ACPG) or ceftriaxone. Patients will be treated with standard regimens of ACPG or ceftriaxone according to Chinese National Guidelines and will be followed up for 12 months. All clinical parameters will be assessed at baseline and at follow-up 3, 6, 9, and 12 months later. The primary outcomes will include cerebrospinal fluid (CSF) white blood cell (WBC) count, serological efficacy, and clinical efficacy. The secondary outcomes will include CSF protein concentrations, Mini-Mental State Examination (MMSE) scores, imaging results, recurrence, and time to recovery from neurosyphilis. Adverse events will be monitored and recorded during the trial. DISCUSSION: This trial will provide clinical data to determine whether ceftriaxone is non inferior to ACPG in treating neurosyphilis and will provide evidence for the improvement of treatment guidelines. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100047164. Registered on 9 June 2021 and updated on 23 November 2021.

[Other Central Nervous System Infections(Including Fungal Infection, Tuberculosis, and Parasitic Infection)].

This review describes cryptococcal meningoencephalitis, tuberculous meningitis, neurosyphilis, and toxoplasma encephalitis. Central nervous system infections are neurological emergencies associated with mortality or other outcomes. Therefore, early diagnosis and treatment are critical. Fungal or gondii infections are rare and affect compromised hosts who are HIV positive, have diabetes, or take immunosuppressive or anticancer drugs. Cryptococcal antigens in the serum and cerebrospinal fluid are useful for the diagnosis of cryptococcal meningoencephalitis. RPR and TPHA tests are useful for the diagnosis of neurosyphilis. Cryptococcal meningoencephalitis and tuberculous meningitis often develop into hydrocephalus, making VP shunt necessary. Antifungal drugs for cryptococcal meningitis are limited by the blood-brain barrier, making a full recovery difficult; in such situations, intraventricular antifungal treatment is required.

Neurosyphilis presenting as autoimmune limbic encephalitis: A case report and literature review.

RATIONALE: Neurosyphilis presenting as limbic encephalitis (LE) is an important differential diagnosis of autoimmune LE (ALE) defined by Graus in 2016. However, data on the clinical differences and similarities between neurosyphilis presenting as LE and ALE are limited. Herein, we report neurosyphilis presenting as ALE that fulfilled the main items of the Graus ALE criteria. Moreover, a literature review of neurosyphilis presenting as LE was performed. PATIENT CONCERNS: A 66-year-old Japanese man developed nonconvulsive status epilepticus. He presented with progressive personality change and working memory deficits within 3 months prior to admission. A hyperintense lesion localized in the bilateral medial temporal area was observed on T2-weighted fluid-attenuated inversion recovery brain magnetic resonance imaging. Cerebrospinal fluid analysis showed mild pleocytosis and the presence of oligoclonal band. However, in-house assays did not detect antineuronal antibodies. Electroencephalogram showed lateralized rhythmic delta activity in the right temporal area. The serum and cerebrospinal fluid serological and antigen tests for syphilis had positive results. DIAGNOSIS: ALE was initially suspected based on the patient's symptoms and ancillary test findings that fulfilled the Graus ALE criteria. However, based on the positive confirmatory test results for syphilis, a diagnosis of neurosyphilis was eventually made. INTERVENTION: The patient received intravenous midazolam, oral levetiracetam, and lacosamide to control nonconvulsive status epilepticus. In addition, he was treated with intravenous benzylpenicillin at a dose of 24 million units/day for 14 days. OUTCOMES: The patient's cognitive function relatively improved after antibiotic treatment. However, he presented with persistent mild working memory deficit, which was evaluated with the Wechsler Adult Intelligence Scale, 3rd edition. Therefore, on day 103 of hospitalization, he was transferred to another hospital for rehabilitation and long-term care due to limitations in performing activities of daily living. LESSONS: The present case was diagnosed with neurosyphilis presenting as ALE, but meanwhile, in most case, neurosyphilis presenting as LE developed at a slower progressive rate, and it had a broader or restricted involvement on brain MRI than ALE based on the literature review. Therefore, an appropriate differential diagnosis of LE can be obtained by identifying clinical differences between the 2 conditions.

Clinical features and incidence of visual improvement following systemic antibiotic treatment in patients with syphilitic uveitis.

To describe the clinical features, longitudinal pattern, and incidence rate of improvement of visual acuity (VA) following antibiotic therapy in patients with syphilitic uveitis. A total of 36 patients were included in this retrospective study from 2009 to 2020. The longitudinal patterns of mean VA values during follow-up were analyzed using a linear mixed model. Most patients were men with HIV coinfection (81%) and presented with panuveitis (49%). The mean VA at baseline improved from 0.97 to 0.39 logMAR at 6 months and remained stable thereafter. The cumulative incidence of VA ≥ 20/25 achieved by 2 years was 70%. Receiving antibiotic therapy within four weeks of the onset of ocular symptoms (adjusted hazard ratio [aHR] 3.4, P = 0.012), absence of HIV coinfection (aHR 8.2, P < 0.001), absence of neurosyphilis (aHR 6.5, P = 0.037), better presenting VA (aHR 5.0, P = 0.003), and intermediate uveitis as opposed to panuveitis (aHR 11.5, P = 0.013) were predictive of achieving VA ≥ 20/25. Men with HIV coinfection represented the majority of our patients. Visual outcomes, in response to antibiotics, were favorable. Delayed treatment, poor presenting VA, presence of HIV coinfection, and concomitant neurosyphilis decreased the likelihood of VA restoration.

Congenital neurosyphilis presenting as neonatal sepsis.

INTRODUCTION: Congenital syphilis involves any organs with various symptoms, including neurological signs. Neurosyphilis is a severe syphilis complication that can develop at any stage of illness. CASE PRESENTATION: A 2,520 g male infant was spontaneously born at term from an untreated syphilis mother. Physical examination revealed decreased consciousness, respiratory distress, seizure, but without neurologic abnormality sign. The serum and cerebrospinal fluid Venereal Disease Research Laboratory and Treponemal Pallidum Hemagglutination Assay TPHA tests titters were 1:16 and 1:1,280, respectively. The diagnosis at admission was respiratory failure and neonatal sepsis. The infant was mechanically ventilated and treated with early management of sepsis. Blood culture was sterile later on. Then, the infant was administered intramuscular benzathine penicillin G (50,000 units/kg/dose) for a total of three weeks. The infant's condition was improved during the treatment. CONCLUSIONS: There are many challenges associated with screening and monitoring neurosyphilis in congenital syphilis. Congenital syphilis presenting as sepsis is easily misdiagnosed as bacterial sepsis.

Investigating latent syphilis in HIV treatment-experienced Ethiopians and response to therapy.

OBJECTIVES: We investigated people with HIV (PWH) receiving combination antiretroviral therapy (cART) for latent syphilis infection prevalence, risk factors, treatment response, and neurosyphilis. METHODS: A prospective follow-up study was conducted on PWH and latent syphilis. The cases were randomly assigned to receive either benzathine penicillin G (BPG) or doxycycline (DOXY), and the posttreatment response was evaluated after 12 and 24 months. The traditional algorithm was used for serodiagnosis, and a semi-quantitative rapid plasma reagin (RPR) test monitored disease activity and treatment effectiveness. RESULTS: Of the 823 participants, 64.8% were women, and the mean age was 41.7±10 years. Thirty-one (3.8%) of the participants (22 males and nine females) had latent syphilis. The risk factors were male sex (aOR = 3.14), increasing age (aOR = 1.04 per year), and cART duration (aOR = 1.01 per month). Baseline RPR titers were: ≤1:4 in 19 (61.3%), between 1:8 and 1:32 in 10 (32.2%), and >1:32 in 2 (6.4%). None of the seven cerebrospinal fluid analyses supported a neurosyphilis diagnosis. In the 12th month of treatment, 27 (87.1%) had adequate serological responses, three (9.7%) had serological nonresponse, and one (3.2%) had treatment failure. Syphilis treatment was repeated in the last four cases with the alternative drug. In terms of adequate serologic response, both therapies were comparable at the 12th month, p = 0.37. All cases responded to treatment in the 24th month. CONCLUSION: In PWH receiving cART, latent syphilis occurred more in men than women, suggesting an investigation of sexual practices and the impact of antenatal syphilis screening. Syphilis disease activity reduces in the latent stage. Therefore, the routine cerebrospinal fluid analysis contributes little to the diagnosis of asymptomatic neurosyphilis and the treatment success of latent syphilis. DOXY is an alternative to BPG, and cART improves serologic response to latent syphilis treatment.