The clinical features of syphilitic myelitis with longitudinally extensive myelopathy on spinal magnetic resonance imaging: a case report and literature review

Background: Syphilitic myelitis as a bacterial infection caused by Treponema pallidum, is a very rare manifestation of neurosyphilis. The magnetic resonance imaging (MRI) appearance of longitudinally extensive myelopathy with syphilitic myelitis is not well documented and only a few cases have been reported about its’ clinical features. Case presentation: Herein, we report a patient who suffered from syphilitic myelitis with symptoms of sensory disturbance, with longitudinally extensive myelopathy with "flip-flop sign" on spinal MRI. This patient performed complete clinical and radiologic recovery after treatment. We also summarized the clinical features of syphilitic myelitis with longitudinally extensive myelopathy from the reported literatures published in English language. A total of 16 articles of 20 cases between January 1987 and December 2018 were identified. Of the 20 patients with syphilitic myelitis, the age of onset varied between 17 and 63 years. Sixteen patients were males (80%). Sixteen patients presented with the onset of sensory disturbance (80%), 15 with paraparesis (75%), 9 with urinary retention (45%). Eleven patients had high risk behavior (55%). Five patients had concomitant HIV infection (25%). Serological data showed 15 patients performed with positive venereal disease research laboratory (VDRL)/ treponema pallidum particle agglutination (TPHA), and 17 patients with positive VDRL/TPHA in cerebrospinal fluid (CSF). Seventeen patients with elevated cells and protein in CSF. On MRI, 16 patients showed abnormal signal intensities involved thoracic spine, 6 involved cervical, and 3 involved both cervical and thoracic spine. There were 3 patients performed with the "flip-flop sign". All the patients were treated with penicillin, and 15 patients were performed with a better prognosis. Conclusions: Syphilitic myelitis relatively rare feature of Treponema pallidum infection. crucial resonance imaging; CSF: cerebrospinal fluid. AQP4: Aquaporin 4.

neurological sequelae. Our case also raises awareness of syphilitic myelitis as an important complication of neurosyphilis due to homosexuality, especially in developing countries.

Introduction
Syphilis is a sexually-transmitted disease caused by Treponema pallidum infection. About 2.1 million pregnant women have active syphilis every year [1]. It is of both individual and public health issue due to its direct morbidity, increased risk of human immunodeficiency virus (HIV) infection and lifelong morbidity especially in low-income countries [2]. It could progress over years through a series of clinical stages and result in irreversible neurological complications without treatment. One-third of patients with early syphilis have the manifestations of central nervous system, and neurosyphilis can also affect the brain, brainstem, spinal cord, meninges, nerve roots, and cerebral/spinal vessels [3]. The clinical presentations of neurosyphilis include acute lymphocytic meningitis (acute syphilitic meningitis), stroke (meningovascular syphilis), dementia (general paresis) and/or myelopathy (tabes dorsalis, meningomyelitis, syringomyelia) [4]. The clinical symptoms of syphilitic meningomyelitis usually develop at between 1 and 30 years after the initial infection [5]. The treatment with penicillin and corticosteroids can diminish the affected lesions with partially reversible. However, symptomatic neurosyphilis especially syphilitic myelitis and the clinical features have been infrequently reported [6].
Only a few cases of syphilitic myelitis have been documented in the international literature.

Case Presentation
A 25-year-old man was admitted to the Department of Neurology with the symptoms of acute onset of sensory disturbance and numbness for 7 days. He was homosexual and exposed to unprotected intercourse. Neurological examination revealed the hypalgesia below T6 level. The other physical examinations were normal. Laboratory tests revealed the treponema pallidum particle agglutination (TPPA) and toluidine red unheated serumtest (TRUST) in serum were positive, and the serum rapid plasma reagin (RPR) was 1:16.
However, antibody against HIV was negative. The levels of homocysteine, folic acid and vitamin B12 were 26μmol/L (0-15μmol/L), 2.59ng/ml ( 5.4ng/ml)) and 325pg/mL (211- With the treatment of penicillin (24-million IU/day) for two weeks, three months later, the symptoms of sensation disappeared. The abnormal hyperintensities of spinal MRI also dissolved with three months' follow up ( Figure 3). Moreover, the laboratory data of CSF showed the reduced cells (24 /uL) and protein (65mg/dl). TPPA and TRUST (1:8) in serum were still positive. The examination in CSF showed TPPA was positive and TRUST was 1:1.
The diagnosis of syphilitic myelitis was established according to the history of homosexuality, clinical manifestations, MRI findings with "flip-flop sign", also with the favorable prognosis by the penicillin treatment.

Literature search and selection
To better understand the clinical characteristics of syphilitic myelitis, we performed a literature search to identify other reports (reviews, case reports or case series) from January 1987 to December 2018, using the PubMed and web of science databases with the following terms, including "syphilis", "neurosyphilis", "syphilitic myelitis", "meningomyelitis", "central nervous system", "spine". All pertinent English language articles were retrieved. A hand-search by reviewing the reference sections of the retrieved articles was also performed.

Data Extraction
Two investigators collected data from the selected articles. The following data were extracted: the author, country, age, gender, symptoms, neurological examination, etiology, auxiliary examinations, therapy and outcome. In this article we also review the literatures of this rare condition.
A total of 16 articles of 20 cases between January 1987 and December 2018 were identified by preliminary literatures. The clinical characteristics of the involved cases were presented in Table 1. Of the 20 patients with syphilitic myelitis, the age of onset varied between 17 and 63 years. Sixteen patients were males (80%). The duration of symptoms was variable from 3 days to 9 months. Sixteen patients presented with the onset of sensory disturbance (80%), 15 with paraparesis (75%), 9 with urinary retention (45%), 2 with gait disorder (10%). Elven patients had a high risk behavior such as homosexuality or bisexuality (55%).
Two patients presented with non-pruritic rash or erythematous with the diagnosis of secondary syphilis (10%). One patient was diagnosed as having syphilis and was treated previously (5%). Five patients had concomitant HIV infection (25%). Serological data showed 15 patients performed with positive venereal disease research laboratory test (VDRL) and/or high Treponema pallidum hemagglutination (TPHA), and 17 patients had positive VDRL/TPHA in CSF. We also found that raised protein was seen in 15 patients and pleocytosis was seen in 17 patients in CSF. On MRI, 16 patients showed abnormal signal intensities involved thoracic spine, 6 involved cervical, and 3 involved both cervical and thoracic spine. There were 3 patients performed with the "flip-flop sign". All the patients were treated with penicillin, and 15 patients were with a better prognosis.

Discussion
Syphilitic myelitis caused by Treponema pallidum is an extremely rare disease. Herein, we reported a rare case of 25-year-old young man presented with symptoms of sensory disturbance, due to syphilitic myelitis with longitudinally extensive myelopathy with "flipflop sign" on spinal MRI. Furthermore, we also summarized the clinical features of syphilitic myelitis with longitudinally extensive myelopathy.
In the pre-antibiotic era, syphilis was one of the most frequent cause of myelopathy [22].
Syphilitic meningomyelitis represents less than 3% of neurosyphilitic cases. The diagnosis is according to a high CSF white blood cell count (≥20mL) with either a reactive CSF VDRL test or a positive CSF antibody [15]. Syphilitic myelitis is a very rare but not well-recognized Although there are several hypotheses, the exact origin of the disease remains unknown [24], which may due to reversible edema from infection or ischemia [13] In syphilitic myelitis, there is primary involvement of the meninges and vessels. It is pathologically characterized by meningeal inflammation and spinal cord ischemia and edema due to syphilitic vasculopathy. The MR abnormalities of the spinal cord probably result from meningeal inflammation and spinal cord ischemia. Spinal cord lesions which have resolved completely following treatment has been reported, and the disappearance of high-signal lesion may indicate that ischemic or inflammatory changes are reversible [25]. As for our case, The high intensity areas on T2-weighted, observed in our case, may indicate reversible ischemic change or inflammation [7].
The strengths of our case are showed as follows. Firstly, our case revealed extensive T2weighted abnormal signal in the spinal cord with "flip-flop sign". To the best of our knowledge, only 2 cases have been previously described of such longitudinally extensive T2-weighted hyperintensities with "flip-flop sign" [9,14]. Secondly, the medical history of homosexuality, clinical presentations, physical examination, laboratory examinations of serum and CSF, the imaging findings of "flip-flop sign", treatment of penicillin and favorable prognosis all contributed to our diagnosis of syphilitic myelitis. Moreover, in view of the longitudinally extensive myelopathy on MRI, we perfected AQP4 in CSF and serum timely.
The result was negative, and the misdiagnose of neuromyelitis optica spectrum disorders had been avoided. Thirdly, to date, our study was the largest number to explore the clinical features of syphilitic myelitis with longitudinally extensive myelopathy on spinal MRI.

Conclusion
In summary, syphilitic myelitis is a very rare manifestation of neurosyphilis. Early diagnosis and treatment are crucial because it represents a treatable and potentially reversible cause of myelopathy with penicillin. Our study also raises awareness of an important complication of neurosyphilis due to homosexuality. Attention is drawn upon the importance of doing serological tests for syphilis when presented with any atypical neurological situation. A high index of suspicion is necessary so that this potentially treatable disease would not be overlooked.

Availability of Data and Materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request Authors' contributions JLY and WXW examined, evaluated the patient and drafted the manuscript. DMX help collect the data. WLH participated in the design of the case-report and helped to draft the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate
The study was approved by the Institutional Ethical Committee of Beijing Chaoyang Hospital, Capital Medical University.

Consent for publication
Written informed consent was obtained from the patient for publication of this Case Report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.