Up to now, only 8 of cases syphilitic myelitis were reported in the world for 30 years[7-13]. The incidence rate of neurosyphilis in the untreated syphilis was 4%-10%, and 1.5% was developed to syphilitic myelitis. It is characterized by paraplegia, numbness and loss of sphincter control. The etiology probably results from thrombosis of the spinal vessels due to syphilitic vasculitis. To the best of our knowledge, the previous published studies described neuroimaging features of syphilitic myelitis and few of them discussed the treatment and clinical prognosis. In this study, we focused on the clinical manifestations, neuroimaging, treatment, as well as clinical prognosis.
The main clinical manifestations of syphilitic myelitis are acute or sub-acute onset of lower limb paralysis, numbness, and urinary dysfunction. This is different from tabes dorsalis which involved posterior column and dorsal root with the symptoms of pain electric shock like in the limbs, loss of reflex of the lower extremity tendon, and deep sensation dysfunction. In this case series, they were acute or sub-acute onset, progressive, legs weakness, impairment of superficial and deep sensation, without weakness and/or numbness of the upper limbs, 3 cases of sensory impairment from low to up, 1 case from buttock to downward. No report has been reported sensory impairment from the hips to feet. One patient had headache, we assumed her meningeal may be involved, but when she had headache, she had not contrast brain MRI to perform my suspect.
To best of our knowledge, no study has reported the specific incubation period between syphilis infection and development of myelitis syphilis based on serology. In this case series, the median time between syphilis infection and development of myelitis symptoms was 10 months (IQR6.5,84; range 6-108). Three out of four (75%) cases developed myelitis syphilis within 2 years of syphilis infection. It suggested that myelitis syphilis should be suspected even in patients with early syphilis who present with myelitis symptoms. Moreover, routine serologic syphilis is critical for prevention of irreversible neurological deficit.
Tashiro firstly described the MRI findings in syphilitic myelitis in 1987. Syphilitic myelitis is usually characterized by long cord lesions, and abnormal enhancement, predominantly in the superficial parts of the spinal cord may be observed on enhanced images. The abnormalities of the spinal cord probably result from meningeal inflammation -induced demyelinating. Spinal cord lesions which have resolved following treatment has been reported, and the disappearance of hyperintensity lesions may indicate that these changes are reversible. In our 4 patients, hyperintensity on T2-weighted images and abnormal enhancement high signal of T1 were seen in the spine. The hyperintensity lesions involved at least three segments of spinal cord, and usually involved the cervical and thoracic spinal cord. This mimicked the imaging findings of NMOSD, but predominantly in the superficial parts of the spinal cord is the specific manifestations of syphilitic myelitis which suggest spinal meninges involvement. In patient 2, hyperintensity were observed in cauda equina and round vertebra. We have not found any report about neurosyphilis involved cauda equina. The severe pain of patient 2 might be related to abnormal signals of nerve root. In patient 1, we discovered thoracic cord atrophy. This imaging manifestation has not been reported. We assumed that the reason of spinal atrophy may be chronic inﬂammation and demyelination, and it suggested that some lesions were irreversible. Lesions from neurosyphilis can be irreversible in the late stage, and atrophy in the spine is considered to be indicative of poor prognosis.
The diagnosis of syphilitic myelitis mainly depends on clinical manifestations, neuroimaging, as well as laboratory tests. Syphilitic myelitis has to be distinguished from other causes of myelitis, e.g. immune-mediated spinal cord diseases, such as acute transverse myelitis, optic neuromyelitis spectrum disease, multiple sclerosis, spinal tumor, such as glioma, metastasis and lymphoma, abscess, HIV induced myelopathy and other specific infections, such as tuberculous myelopathy, cryptococcal myelopathy. Serologic and CSF tests are the key to diagnosis. All patients were negative for antibodies against AQP-4, and hyperintensity in the spine on T2-weighted MRI were diminished or improved after antibiotic treatment, it can exclude NMOSD.
Serologic SS-A, Ro-52 and SS-B were positive in patient 3, but her symptom was improved and the MRI lesions were disappeared after penicillin treatment. There is no report of autoimmune diseases caused by treponema pallidum. We should pay attention to the relationship between syphilis and autoimmune bodies, and follow up those biomarkers.
Early diagnosis of neurosyphilis and appropriate antibiotic treatment can result in clinical improvement. The diagnostic challenges illustrate the importance of comprehensive evaluation, including laboratory and neuroimaging examinations should be emphasized. Neurosyphilis is considered to be a treatable disease with early diagnosis and treatment. According to existing literature, the first-choice treatment for neurosyphilis is intravenous penicillin. Patient 2 was originally misdiagnosed with demyelination for 7 years before receiving anti-syphilis treatment. Symptoms showed no obvious improvement after treatment for neurosyphilis. The remaining 3 patients received anti-syphilis treatment timely and their symptoms did improve to varying degrees upon follow-up. As we know, this is the first paper to discuss the treatment and long follow-up time.
It was common corticosteroid was given before and during antibiotic therapy in order to prevent the Jarish - Herxheimer reaction. However, as we know, there have been no clinical studies regarding the usefulness of corticosteroid therapy for syphilitic myelitis. However, our case series suggested that corticosteroids may be useful as an adjunctive treatment. Previous study revealed that treatment of systemic corticosteroids may be an important adjunctive therapy for early neurosyphilis presenting with multiple cranial nerve palsies. Moreover, there have been a few reports of gumma treated by corticosteroids without antibiotics. Therefore, corticosteroid treatment could be effective in some clinical forms of neurosyphilis, such as cranial neuropathy, syphilitic myelitis, and gumma. In my study, Patient 1 and patient 3 received combined antibiotics-corticosteroid treatment and the effectiveness of corticosteroid therapy as an adjunctive treatment to improve neurological functions was well. We speculate the reason may be related to corticosteroid can reduce spinal cord edema and inhibit inflammation. Patient 2 only received corticosteroid therapy before penicillin therapy, suggesting that corticosteroid therapy was only adjuvant therapy, penicillin should be given as soon as possible.
In conclusion, syphilitic myelitis is rare, and clinical and imaging are not specific, hence high misdiagnosis was observed, which prevents patients receiving appropriate and early treatment, and often results in more severe neurologic damage. When encountering long-segment hyperintensity spinal cord lesions, we should think of syphilis and undergo related biomarker test, and all patients should undergo CSF examination as soon as possible when TRUST are positive in serum. Prompt diagnosis and combined antibiotics-corticosteroid therapy may improve neurological prognosis.
Limitations of this study include the small single center nature of our study. Secondly, the number of patients enrolled is low, which may result in the selection bias. Further studies with multi-center randomized findings are needed.