Treatment Challenges in a Severe Case of Syphilitic Myelitis With a Longitudinally Extensive Spinal Cord Lesion

Abstract

Syphilitic myelitis is an unusual manifestation of neurosyphilis, rarely reported in the literature. The best management approach remains unclear in severe cases with longitudinally extensive spinal cord lesions. We describe a 29-year-old man with a history of incompletely treated syphilis after a high-risk sexual encounter, who presented two years later with several weeks of progressive numbness and weakness in both legs. MRI spine showed significant cord expansion from the craniocervical junction to T6 with patchy cord enhancement. He was diagnosed with syphilitic myelitis given his history of inadequately treated syphilis, positive serum rapid plasma reagin at a high titer, and CSF pleocytosis with elevated protein along with a reactive CSF Venereal Disease Research Laboratory test. Alternative infectious or immunological etiologies were excluded. He was treated with IV penicillin and pulse steroid therapy with IV methylprednisolone 1 g daily for 3 days with improvement. However, he was soon readmitted with recurrent weakness requiring an additional course of pulse steroid therapy followed by a short prednisone taper. Afterward, his symptoms recurred with worsened cord expansion on imaging. He was re-treated with IV penicillin and pulse steroid therapy with a more prolonged prednisone taper. The patient subsequently improved and had no further recurrent symptoms on extended outpatient follow-up. This report illustrates the importance of keeping syphilitic myelitis on the differential as a treatable cause of longitudinally extensive myelopathy. The patient may have benefited from high-dose IV steroids with a prolonged taper while waiting for the full treatment effect of antibiotics.

Introduction

The spirochete, Treponema pallidum, primarily spread through sexual contact and blood transmission, is the infectious agent that causes syphilis. At any time during the course of the disease, neurosyphilis can develop as a result of the organism invading the central nervous system. ¹ The clinical presentations of neurosyphilis are varied and include meningitis, stroke (via meningovascular involvement), dementia, and myelopathy (including tabes dorsalis and meningomyelitis). ¹

Syphilitic myelitis is a rare manifestation of neurosyphilis, estimated to represent less than 3% of neurosyphilis cases. ² Confined only to the spinal cord, diagnosis can be difficult due to similarities in clinical symptoms and imaging appearance to mimics such as idiopathic transverse myelitis, neuromyelitis optica spectrum disorder (NMOSD), and anti-myelin oligodendrocyte glycoprotein (anti-MOG) syndromes. It is even more unusual for patients with neurosyphilis to have a longitudinally extensive myelopathy, with only a few cases reported in the literature.^2-8

The best management approach to patients with longitudinally extensive syphilitic myelitis is not entirely clear. A recent literature review of 20 published cases reported various treatment approaches, some with penicillin alone and some with a combination of penicillin and steroids, with a majority of cases having a good prognosis in the form of reduced lesions on repeat MRI. ² Here, we discuss a rare and severe case of longitudinally extensive syphilitic myelitis requiring multiple courses of steroids in addition to antibiotics for clinical improvement.

Case

A 29-year-old man with a history of incompletely treated syphilis after a high-risk sexual encounter presented two years later with several weeks of progressive numbness and weakness in his bilateral lower extremities. Neurological exam showed pupils that constricted more to accommodation than light, 4/5 diffuse weakness in bilateral lower extremities, and mild bilateral hand weakness. He had a T6 sensory level, and sensation in his lower extremities was impaired to vibration and proprioception. He had hyperreflexia in his patella bilaterally with an extensor plantar response in his left lower extremity. Complete blood count and comprehensive metabolic panel were normal. His COVID-19 test was negative. He was HIV negative. Rapid plasma reagin (RPR) was positive at 1:64 titer.

MRI spine showed significant spinal cord expansion from the craniocervical junction to the level of T6 with patchy cord enhancement extending from C6 to T1 and an additional enhancing focus at C4 (Figure 1). His MRI also showed a characteristic “flip-flop sign” from C6 to T1 in which the location of the abnormal enhancement on a T1-weighted post-contrast image corresponds to hypointensity in a T2-weighted image. ⁹ Axial images showed that the marked enhancement at C6‐C7 was primarily in the dorsal cord. MRI brain was normal. CSF showed a lymphocytic pleocytosis (17/uL), elevated protein (171 mg/dL), and normal glucose. CSF bacterial and fungal cultures were negative, and no acid-fast bacteria were isolated at 6 weeks in the CSF. Testing for tuberculosis via an IFN-gamma release assay was negative. Viral studies, including West Nile virus, herpes simplex virus, enterovirus, varicella-zoster virus, and cytomegalovirus, were negative. Cytology and flow cytometry were negative for malignancy. CSF Venereal Disease Research Laboratory (VDRL) test was reactive at 1:4 titer. Serum cell-based assays for aquaporin-4 receptor and MOG antibodies were negative.

He was started on IV penicillin for a total 14-day course. He was also treated with IV methylprednisolone 1g daily for 3 days. His strength improved to near baseline after completion of the pulse steroid therapy, and he was discharged. However, he returned a few days later with rapidly worsening lower extremity weakness and inability to walk before his penicillin course was completed. Repeat MRI cervical and thoracic spine demonstrated increased cervicothoracic cord enhancement and surrounding cord edema. He was given an additional 5 days of IV methylprednisolone 1g daily, and he completed his antibiotic course. His weakness and gait significantly improved such that his strength was 4+/5 in his bilateral lower extremities and he could ambulate household distances with a walker and use stairs at supervision level. He was discharged with a 15-day prednisone taper and physical therapy.

Ten days after completion of the prednisone taper, he was readmitted with recurrent progressive worsening of his lower extremity weakness, including more difficulty standing with his walker, as well as urinary retention and muscle spasms in his lower back. MRI spine showed increased cord edema and enhancement centered at C6‐C7. Repeat serum RPR titer was 1:32. Repeat CSF revealed a lymphocytic pleocytosis (44/uL) with elevated protein (354 mg/dL). VDRL in the CSF was reactive at a titer of 1:2. Repeat flow cytometry and cytology were negative for malignancy. A CT scan of his chest, abdomen, and pelvis revealed no evidence of sarcoidosis or malignancy. He was restarted on IV methylprednisolone 1 g daily for 5 days and IV penicillin for an additional 14 days. A repeat MRI cervical and thoracic spine following IV steroids showed significant interval improvement of the spinal cord edema. Clinically, the patient had a significant improvement in strength, and he was discharged with a slower 27-day prednisone taper and physical therapy. The patient completed the steroid taper with no recurrent symptoms. On outpatient follow-up approximately 2.5 month later, he endorsed continued improvement in gait (improved to using a cane from a walker), though with persistent back and bilateral lower extremity spasms.

Figure 1.

Cervical and thoracic spinal cord magnetic resonance imaging showing extensive cervical cord hyperintense lesions and cord expansion on sagittal T2-weighted (A) and short tau inversion recovery (STIR) (B) sequences. The cord edema extends to the level of T6, as seen on STIR sequence of the thoracic spinal cord (C). There is corresponding enhancement on a T1-weighted image with gadolinium of the cord from C6 through T1 (D) and an additional focus of enhancement at C4 (E, red arrow). A T1-weighted axial image with gadolinium (F) is at the level of C6‐C7 and shows a predilection for the dorsal cord. Yellow arrows show the characteristic “flip-flop” sign in which corresponding hypointensity in a T2-weighted image is seen at the location of abnormal enhancement on a T1-weighted post-contrast image.

Discussion

This is a complex case of a patient with a rare presentation of neurosyphilis in the form of longitudinally extensive syphilitic myelitis. The patient initially improved with IV penicillin and pulse steroid therapy, but his symptoms and myelitis recurred when his steroids wore off, and he was readmitted. During readmission, his CSF pleocytosis worsened despite an improvement in his serum RPR and CSF VDRL while on antibiotic treatment. While the exact reason remains unclear, the degree of his worsened CSF pleocytosis was consistent with what is reported in other published case reports of syphilitic myelitis (with CSF pleocytosis improving after several months of treatment). ² It was not until our patient was given a regimen of pulse dose steroids with a much longer steroid taper along with an additional course of IV penicillin that he had sustained improvement without recurrent symptoms.

Neurosyphilis can present at any stage of the disease and can infiltrate any component of the central nervous system. ¹⁰ Syphilitic myelitis is a unique manifestation of neurosyphilis with involvement limited to the spinal cord. A systematic review of 20 published cases of syphilitic myelitis found that the most commonly reported symptoms were sensory disturbance (80%), followed by paraparesis (75%), urinary retention (45%), and gait disturbance (10%). ² The diagnosis of syphilitic myelitis depends on clinical manifestations, laboratory tests, and imaging characteristics. Laboratory findings consistent with syphilitic myelitis include CSF studies with elevated protein, pleocytosis, and positive VDRL or Treponema pallidum hemagglutination assay (TPHA). ¹¹ As clinical and radiographic features overlap significantly, NMOSD and anti-MOG syndromes must be ruled out, preferably with serum cell-based assays. Other alternative etiologies that can cause myelitis should be excluded, including spinal tumor, abscess, demyelinating lesions, and tuberculosis, among others.

MRI findings in syphilitic myelitis are varied and non-specific; however, they commonly include high-intensity parenchymal lesions in multiple levels of the spinal cord on T2-weighted imaging and abnormal gadolinium-enhancement on T1-weighted images. ⁹ Unique features include the “flip-flop sign,” in which corresponding hypointensity in T2-weighted imaging is seen at locations of abnormal enhancement on T1-weighted images; and the “candle guttering appearance” of enhancing lesions in the peripheral cord parenchyma, just under the pia mater. ⁹ These features are suggestive of a combination of inflammatory and ischemic processes, and superficial enhancing lesions have been interpreted to indicate that the pathophysiology of syphilitic myelitis involves an invasion of the spinal cord from the surface. ⁹ Improvement and sometimes even complete resolution of MRI abnormalities have been demonstrated following treatment, suggesting the reversible nature of these pathologic processes, as well as the utility of MRI in monitoring treatment response.^12,13

The resolution of CSF abnormalities in conjunction with clinical improvement/stabilization is generally how clinicians judge the success of neurosyphilis treatment. The recommended treatment for patients with neurosyphilis is IV aqueous penicillin G at 18‐24 million units per day for 10‐14 days. Steroids, such as prednisolone, are frequently added. ¹⁴ The rationale for giving steroids with anti-treponemal antibiotics is based on the concern that neurological lesions can progress despite adequate treatment for syphilis. ¹⁵ Treatment regimens are varied when it comes to adjunctive use of systemic steroids. Treatment regimens have ranged from IV antibiotics alone to IV antibiotics plus systemic steroids, including prednisolone, dexamethasone, and methylprednisolone.^2,16 It can take up to 12 months for CSF white blood cell counts and VDRL to normalize after treatment of neurosyphilis, with HIV-positive patients not on antiretroviral therapy potentially having a slower rate of normalization.^17,18 In severe cases, such as in our patient, simultaneous treatment with steroids while on IV penicillin can help improve or stabilize myelopathic symptoms while waiting for the full treatment effect of antibiotics. However, it should be emphasized that there have been no clinical studies regarding the usefulness of systemic steroid therapy for syphilitic myelitis. While other case reports have also suggested that a combined antibiotic corticosteroid treatment can improve neurological prognosis,^2,16 we are limited in presenting only a single case of our experience with this treatment approach, and further clinical trials are needed.

ORCID iDs

Amy Li Safadi https://orcid.org/0000-0002-3610-4456

Prerna Malla https://orcid.org/0000-0001-5718-3272