- Email: [email protected]
Neurosyphilis presenting with myelitis-case series and literature review
J Infect Chemother xxx (xxxx) xxx
Contents lists available at ScienceDirect
Journal of Infection and Chemotherapy journal homepage: http://www.elsevier.com/locate/jic
Case Report
Neurosyphilis presenting with myelitis-case series and literature review Yali Wu, Wenqing Wu* Department of Neurology, Beijing Ditan Hospital, Capital Medical University, No. 8 East Jing Shun Rd, Chaoyang District, Beijing, 100015, China
a r t i c l e i n f o
a b s t r a c t
Article history: Received 22 April 2019 Received in revised form 21 August 2019 Accepted 16 September 2019 Available online xxx
Syphilitic myelitis is an extremely rare manifestation of neurosyphilis and often misdiagnosed. However, a small amount of literature describe its clinical manifestations and neuroimaging features, and there is no relevant data on the prognosis, especially the long follow-up prognosis. In this paper, four syphilitic myelitis patients admitted to our hospital between July 2012 and July 2017 were retrospectively reviewed. Of the four patients, two females and two males. Treatment included intravenous penicillin G, with 24 million units of penicillin G per day administered intravenously for 14 days. Three patients were also treated with corticosteroids. The prognosis were well in three cases who received early anti-syphilis treatment, but one case who received delayed treatment due to misdiagnosis had no improvement. Neurosyphilis should be considered when there is long-segment myelopathy. Anti-treponemal antibiotics and corticosteroid therapy may improve neurological prognosis. © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Keywords: Syphilis Neurosyphilis Magnetic resonance imaging
1. Background Neurosyphilis (NS) is a chronic infectious disease of central nervous system (CNS) caused by treponema pallidum [1]. Neurosyphilis involving spinal cord mainly include tabes dorsalis and syphilitic myelitis. Tabes dorsals is common type of neurosyphilis. Tabes dorsalis involves spinal posterior column and dorsal root, and the symptoms include pain electric shock like in the limbs, loss of reflex of the lower extremity tendon, and deep sensation dysfunction. The spinal magnetic resonance imaging (MRI) is always normal [2]. However, the main clinical manifestations of syphilitic myelitis are acute or sub-acute onset of lower limb paralysis, numbness, and urinary dysfunction. The diagnosis criteria are applied: (1) diagnosis of myelitis established by two experienced neurologist based on symptoms and longitudinally extensive transverse myelitis (LETM) at the cervical and thoracic levels mimicked neuromyelitis optic (NMO) on MRI; (2) NS was diagnosed by positive treponema pallidum particle assay (TPPA) and toluidine red untreated serum test (TRUST) in the serum and cerebrospinal fluid (CSF); (3) negative human immunodeficiency
* Corresponding author. E-mail address: [email protected] (W. Wu).
virus (HIV) and serum anti-aquaporin 4 (AQP-4), as well as negative bacterial, fungal, virus, or mycobacterium tuberculosis in the CSF. As we know, CSF venereal disease research laboratory (VDRL) test is the reference test for the laboratory diagnosis of NS. However, there are no commercial VDRL reagents approved by the State Food and Drug Administration for VDRL examination in China. There are research suggesting that TRUST can be considered as an alternative test for NS diagnosis when the VDRL is not available [3]. In this study, CSF TRUST is used to diagnose NS, given that the specificity and sensitivity of TRUST are similar to VDRL and rapid plasma reagin (RPR), but they are easier and less expensive to perform [4]. We used the modified Rankin Scale (mRS) to assess the degree of neurological deficit. 2. Case presentation Patient 1, a 43-year-old female, who had rash of legs in August 2011, presented with numbness and weakness in the bilateral feet. MRI showed long lesions in the cervical and thoracic cord. She was diagnosed acute myelitis. She received prednisolone 500mg for 5 days, then prednisone 60mg/day. However, her symptoms got deteriorated. She felt her legs weaker, and she could not walk as well as before. The numbness extended to the chest and she had urinary dysfunction. In March 2013, lumbar puncture was performed. CSF TRUST was 1:4. Serum TRUST was 1:32. mRS was 4.
https://doi.org/10.1016/j.jiac.2019.09.007 1341-321X/© 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Please cite this article as: Wu Y, Wu W, Neurosyphilis presenting with myelitis-case series and literature review, J Infect Chemother, https:// doi.org/10.1016/j.jiac.2019.09.007
2
Y. Wu, W. Wu / J Infect Chemother xxx (xxxx) xxx
There was high intensity in T1-3 cord (Fig. 1A). She was diagnosed syphilitic myelitis and started anti-treponemal antibiotics. Followup 6 years, The numbness was disappeared, only leaving slight weakness in the left limb. mRS was 1. CSF TRUST was negative. Serum TRUST was 1:2. The cervical MRI was normal, and the thoracic cord was atrophy (Fig. 1B). Patient 2, a 69-year-old male, who had genital ulcer, was diagnosed syphilis and did not receive treatment. After 9 years, he presented with backache and chest tightness. There were lesions in the thoracic central cord (T5-8). He received oral steroid hormone 30e60mg therapy many times. However, he had difficulty in walking and urinary incontinence. MRI showed lesions in T6-7 cord, medullary cone and cauda equina (Fig. 1C). mRS was 4. CSF TRUST was 1:1. Serum TRUST was 1:16. He was diagnosed syphilitic myelitis and received anti-treponemal antibiotic treatment. After 1 year, he suffered serious neurological deficit despite improvement in the MRI. mRS was 4. Serum TRUST was 1:8. CSF TRUST was negative. The thoracic MRI was normal, leaving lesion in the cauda equina. Patient 3, a 42-year-old female, who had rash and diagnosed syphilis, received 2.4 million units IM once per week for up to 3 weeks, and the rash disappeared. After 8 months, she presented with chest pain and feet numbness. Then she had legs weakness, thorax and back hyperalgesia. mRS was 2. CSF TRUST was 1:1. Serum TRUST was 1:32. T2-weighted MRI showed hyperintensity lesions in cervical and thoracic spinal cord, and enhancement in T1. She was diagnosed syphilitic myelitis. She started anti-treponemal antibiotics and prednisolone 60 mg for 7 days, and prednisolone was decreased 10mg per week. After 1 year, her symptoms
improved, only leaving numbness in the left leg. mRS was 1. Serum TRUST was 1:8. CSF TRUST was negative. There was no hyperintensity in the spinal cord. Patient 4, a 30-year-old male, presented syphilic rash and did not receive treatment. After 4 months, he presented with bilateral numbness of hips. mRS was 1. There were hyperintensity lesions in cervical and thoracic spinal cord, and enhancement in the superficial portion at C4-T1 (Fig. 1D, 1E). Serum TRUST was 1:4. CSF TRUST was 1:1. He was diagnosed syphilitic myelitis and started anti-treponemal antibiotics. After 6 months, his neurological symptoms disappeared. mRS was 0. Serum TRUST was 1:4. CSF TRUST was negative. There was no enhancement in spinal cord (Fig. 1F, and Tables 1e3). 3. Discussion and conclusions Up to now, the incidence rate of neurosyphilis in the untreated syphilis is 4%e10%, and 1.5% is developed to syphilitic myelitis [5]. Syphilitic myelitis can present with lower extremity weakness, sensory disturbance, and bladder or bowel dysfunction. Tashiro [6] firstly described the MRI characteristics of 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. 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 the changes are reversible [7]. In patient 2, hyperintensity was observed in cauda equina and round vertebra.
Fig. 1. A. T2-weighted MRI showing hyperintensity areas in the T1eT3 in Patient1. B. T2-weighted MRI showing atrophy in thoracic spinal cord in patient 1. C. enhanced image showing enhancement in cauda equina in patient 2. D. T2-weighted MRI showing high intensity areas in the C4-T2 in Patient 4. E. enhancement in the superficial portion of C4eT2 in Patient 4. F. T2-weighted MRI showing high intensity areas disappeared.
Please cite this article as: Wu Y, Wu W, Neurosyphilis presenting with myelitis-case series and literature review, J Infect Chemother, https:// doi.org/10.1016/j.jiac.2019.09.007
Y. Wu, W. Wu / J Infect Chemother xxx (xxxx) xxx
3
Table 1 The clinical manifestations and MRI of the syphilitic myelitis. Case Sex Age (years) Form of onset Duration 1
F
43
subacute
2
M
69
subacute
3
F
43
subacute
8 months
4
M
30
subacute
2 months
Clinical symptoms
20 months bilateral feet numbness and weakness, astriction, frequency of urinatiorunable to walk and numbness extended to the chest and urinary incontinence 2 years backache and chest distension. Symptoms got deteriorated, numbness and weakness in the legs until difficulty in walking, urinary incontinence.
chest and back pain, then numbness in the feet, and the numbness gradually appeared to her legs, to Saddle area weakness in her legs and hyperalgesia of thorax and back below bilateral articulatio coxae. bilateral hips numbness of gradually developed to the feet
Clinical signs
MRI
left limb weakness with a grade of 4. Bilateral positive babinski sign
T2 showed high intensity in T1-3 spinal cord
left limb weakness with a grade of 4 e5, right limb weakness with a grade of 4. Positive right babinski sign. Superficial sensory disturbance and diminished vibratory below the level of T6 bilateral limbs weakness with a grade of 5-.the feet vibratory (), Superficial sensory disturbance
T2 showed high intensity in T6-7, medullary cone and caudaequina
bilateral positive hoffmann signs, sense pain was impaired below T2.
T2 showed high intensity in cervical and thoracic spinal cord, enhancement in thoracic cord in T1
T2 showed high intensity in C4eT4, enhancement in the superficial portion of C4eT1
The duration is a time from appearing symptoms until diagnosed of neurosyphilis.
Table 2 The laboratory data and therapy of syphilitic myelitis. Case
TRUST (serum)
TRUST (csf)
TPPA (serum)
TPPA (csf)
Pressure
WBC (cells/mm3)
Pro (mg/dl)
OB
AQP-4
Therapy
1 2 3 4
1:32 1:16 1:32 1:8
1:4 1:1 1:2 1:1
þ þ þ þ
þ þ þ þ
150 120 170 130
7 8 88 7
111 138 59 53
e e e e
e e e e
Penicillin Penicillin Penicillin Penicillin
Table 3 The clinical symptoms, laboratory data and MRI after treatment. Case
Clinical symptoms
TRUST (serum)
TRUST (csf)
WBC
Pro
MRI
1 2 3 4
improvement deteriorated normal improvement
1:1 1:8 1:8 1:4
e e e e
4 1 4 4
25.6 106.7 34 42.9
thoracic spinal cord atrophy The thoracic spinal cord was normal, leaving lesions in the caudaequina cervical spinal cord atrophy T2 showed high intensity in T2eT4, enhancement in the superficial portion of C4eT1
We have not found any report about neurosyphilis involving cauda equina. The severe pain might be related to abnormal signals of nerve root. In patient 1, we discovered thoracic cord atrophy. The imaging manifestation has not been reported. We assumed the reason may be chronic inflammation and demyelination [8]. Lesions from neurosyphilis can be irreversible in the late stage, and spine atrophy is considered to be indicative of poor prognosis. The diagnosis of syphilitic myelitis mainly depends on clinical manifestations, MRI, and 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 and cryptococcal myelopathy. All patients were negative AQP-4. Hyperintensity of T2-weighted MRI was diminished or improved after antibiotic treatment. These can exclude NMOSD [9]. Corticosteroid should be given with all anti-treponemal antibiotics for neurological and cardiovascular syphilis because cardiovascular and neurological lesions may progress despite adequate treatment for syphilis [10]. However, there have been no clinical studies regarding the usefulness of corticosteroid therapy for syphilitic myelitis. Our cases suggested corticosteroids may be useful as an adjunctive treatment for syphilitic myelitis. Previous study have revealed that corticosteroids may be an important
adjunctive therapy for early neurosyphilis presenting with multiple cranial nerve palsies [11]. Moreover, there were a few reports of gumma treated by corticosteroids without antibiotics [12]. In my study, Patient 1 and patient 3 received antibiotics-corticosteroid treatment to improve neurological functions. Patient 2 only received corticosteroid therapy before penicillin therapy, suggesting that corticosteroid therapy was only an adjunctive therapy, and anti-treponemal antibiotics should be given as soon as possible. Syphilitic myelitis is an extremely rare disease. When encountering long-segment myelopathy, we should consider the possibility of syphilitic myelitis. All myelitis patients should undergo CSF examination as soon as possible when serum TRUST is positive. Prompt diagnosis and combined antibiotics-corticosteroid therapy may improve the neurological prognosis. Abbreviations AQP4 CSF MRI NMOSD OB TRUST TPPA HIV
Anti-aquaporin 4 Cerebrospinal fluid Magnetic resonance imaging Neuromyelitis optic spectrum disorder Oligoclonal bands toluidine red untreated serum test Treponema pallidum particle assay human immunodeficiency virus
Please cite this article as: Wu Y, Wu W, Neurosyphilis presenting with myelitis-case series and literature review, J Infect Chemother, https:// doi.org/10.1016/j.jiac.2019.09.007
4
Y. Wu, W. Wu / J Infect Chemother xxx (xxxx) xxx
VDRL RPR CNS LETM mRS
venereal disease research laboratory rapid plasma regain central nervous system longitudinally extensive transverse myelitis modified Rankin Scale
Conflicts of interest The authors declare that they have no competing interests. References [1] Fenton KA, Breban R, Vardavas R, Okano JT, Martin T, Aral S, et al. Infectious syphilis in high-income settings in the 21st century. Lancet Infect Dis 2008;8(4):244e53. https://doi.org/10.1016/S1473-3099(08)70065-3. [2] Berger JR. Neurosyphilis and the spinal cord: then and now. J Nerv Ment Bhai Dis 2011. https://doi.org/10.1097/NMD.0b013e31823928e8. [3] Gu W, Yang Y, Wu L, Yang S, Ng LK. Comparing the performance characteristics of CSF-TRUST and CSF-VDRL for syphilis: a cross-sectional study. BMJ Open 2013. https://doi.org/10.1136/bmjopen-2012-002204. [4] Zhu L, Gu X, Peng RR, Wang C, Gao Z, Zhou P, et al. Comparison of the cerebrospinal fluid (CSF) toluidine red unheated serum test and the CSF rapidplasma reagin test with the CSF venereal disease research laboratory test for
[5]
[6]
[7]
[8] [9]
[10]
[11]
[12]
diagnosis of neurosyphilis among HIV-negative syphilis patients in China. J Clin Microbiol 2014. https://doi.org/10.1128/JCM.02522-13. Conde-Sendín MA, Amela-Peris R, Aladro-Benito Y, Maroto AA. Current clinical spectrum of neurosyphilis in immunocompetent patients. Eur Neurol 2004;52(1):29e35. Tashiro K, Moriwaka F, Sudo K, Akino M, Abe H. Syphilitic myelitis with its magnetic resonance imaging (MRI) verification and successful treatment. Jpn J Psychiatry Neurol 1987;41(2):269e71. Kararizou E, Anagnostou E, Kapaki E, Davaki P. Chronic inflammatory demyelinating polyneuropathy associated with neurosyphilis. Am J Med Sci 2015. https://doi.org/10.1097/MAJ.0000000000000369. Marra CM. Syphilis screening in neurology. JAMA Neurol 2016. https://doi.org/ 10.1001/jamaneurol.2016.1955. Yuan Jun Liang, Wang Wei Xue, Hu Wen-Li. Clinical features of syphilitic myelitis with longitudinally extensive myelopathy on spinal magnetic resonance imaging. World J Clin Cases 2019;7(11):1282e90. Kingston M, French P, Higgins S, McQuillan O, Sukthankar A, Stott C, et al. UK national guidelines on the management of syphilis 2015. Int J STD AIDS 2016;27:421e46. Komamura H, Nakamura T, Kobayashi J, Harada R, Endo K, Ogura M, et al. Early neurosyphilis presenting with multiple cranial nerve palsies: a case report of management by combined penicillin-corticosteroid treatment. J Infect Chemother 2019. https://doi.org/10.1016/j.jiac.2018.11.007. Herrold JM. A syphilitic cerebral gumma manifesting as a brain-stem mass lesion that responded to corticosteroid monotherapy. Mayo Clin Proc 1994;69(10):960e1.
Please cite this article as: Wu Y, Wu W, Neurosyphilis presenting with myelitis-case series and literature review, J Infect Chemother, https:// doi.org/10.1016/j.jiac.2019.09.007
Contents lists available at ScienceDirect
Journal of Infection and Chemotherapy journal homepage: http://www.elsevier.com/locate/jic
Case Report
Neurosyphilis presenting with myelitis-case series and literature review Yali Wu, Wenqing Wu* Department of Neurology, Beijing Ditan Hospital, Capital Medical University, No. 8 East Jing Shun Rd, Chaoyang District, Beijing, 100015, China
a r t i c l e i n f o
a b s t r a c t
Article history: Received 22 April 2019 Received in revised form 21 August 2019 Accepted 16 September 2019 Available online xxx
Syphilitic myelitis is an extremely rare manifestation of neurosyphilis and often misdiagnosed. However, a small amount of literature describe its clinical manifestations and neuroimaging features, and there is no relevant data on the prognosis, especially the long follow-up prognosis. In this paper, four syphilitic myelitis patients admitted to our hospital between July 2012 and July 2017 were retrospectively reviewed. Of the four patients, two females and two males. Treatment included intravenous penicillin G, with 24 million units of penicillin G per day administered intravenously for 14 days. Three patients were also treated with corticosteroids. The prognosis were well in three cases who received early anti-syphilis treatment, but one case who received delayed treatment due to misdiagnosis had no improvement. Neurosyphilis should be considered when there is long-segment myelopathy. Anti-treponemal antibiotics and corticosteroid therapy may improve neurological prognosis. © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Keywords: Syphilis Neurosyphilis Magnetic resonance imaging
1. Background Neurosyphilis (NS) is a chronic infectious disease of central nervous system (CNS) caused by treponema pallidum [1]. Neurosyphilis involving spinal cord mainly include tabes dorsalis and syphilitic myelitis. Tabes dorsals is common type of neurosyphilis. Tabes dorsalis involves spinal posterior column and dorsal root, and the symptoms include pain electric shock like in the limbs, loss of reflex of the lower extremity tendon, and deep sensation dysfunction. The spinal magnetic resonance imaging (MRI) is always normal [2]. However, the main clinical manifestations of syphilitic myelitis are acute or sub-acute onset of lower limb paralysis, numbness, and urinary dysfunction. The diagnosis criteria are applied: (1) diagnosis of myelitis established by two experienced neurologist based on symptoms and longitudinally extensive transverse myelitis (LETM) at the cervical and thoracic levels mimicked neuromyelitis optic (NMO) on MRI; (2) NS was diagnosed by positive treponema pallidum particle assay (TPPA) and toluidine red untreated serum test (TRUST) in the serum and cerebrospinal fluid (CSF); (3) negative human immunodeficiency
* Corresponding author. E-mail address: [email protected] (W. Wu).
virus (HIV) and serum anti-aquaporin 4 (AQP-4), as well as negative bacterial, fungal, virus, or mycobacterium tuberculosis in the CSF. As we know, CSF venereal disease research laboratory (VDRL) test is the reference test for the laboratory diagnosis of NS. However, there are no commercial VDRL reagents approved by the State Food and Drug Administration for VDRL examination in China. There are research suggesting that TRUST can be considered as an alternative test for NS diagnosis when the VDRL is not available [3]. In this study, CSF TRUST is used to diagnose NS, given that the specificity and sensitivity of TRUST are similar to VDRL and rapid plasma reagin (RPR), but they are easier and less expensive to perform [4]. We used the modified Rankin Scale (mRS) to assess the degree of neurological deficit. 2. Case presentation Patient 1, a 43-year-old female, who had rash of legs in August 2011, presented with numbness and weakness in the bilateral feet. MRI showed long lesions in the cervical and thoracic cord. She was diagnosed acute myelitis. She received prednisolone 500mg for 5 days, then prednisone 60mg/day. However, her symptoms got deteriorated. She felt her legs weaker, and she could not walk as well as before. The numbness extended to the chest and she had urinary dysfunction. In March 2013, lumbar puncture was performed. CSF TRUST was 1:4. Serum TRUST was 1:32. mRS was 4.
https://doi.org/10.1016/j.jiac.2019.09.007 1341-321X/© 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Please cite this article as: Wu Y, Wu W, Neurosyphilis presenting with myelitis-case series and literature review, J Infect Chemother, https:// doi.org/10.1016/j.jiac.2019.09.007
2
Y. Wu, W. Wu / J Infect Chemother xxx (xxxx) xxx
There was high intensity in T1-3 cord (Fig. 1A). She was diagnosed syphilitic myelitis and started anti-treponemal antibiotics. Followup 6 years, The numbness was disappeared, only leaving slight weakness in the left limb. mRS was 1. CSF TRUST was negative. Serum TRUST was 1:2. The cervical MRI was normal, and the thoracic cord was atrophy (Fig. 1B). Patient 2, a 69-year-old male, who had genital ulcer, was diagnosed syphilis and did not receive treatment. After 9 years, he presented with backache and chest tightness. There were lesions in the thoracic central cord (T5-8). He received oral steroid hormone 30e60mg therapy many times. However, he had difficulty in walking and urinary incontinence. MRI showed lesions in T6-7 cord, medullary cone and cauda equina (Fig. 1C). mRS was 4. CSF TRUST was 1:1. Serum TRUST was 1:16. He was diagnosed syphilitic myelitis and received anti-treponemal antibiotic treatment. After 1 year, he suffered serious neurological deficit despite improvement in the MRI. mRS was 4. Serum TRUST was 1:8. CSF TRUST was negative. The thoracic MRI was normal, leaving lesion in the cauda equina. Patient 3, a 42-year-old female, who had rash and diagnosed syphilis, received 2.4 million units IM once per week for up to 3 weeks, and the rash disappeared. After 8 months, she presented with chest pain and feet numbness. Then she had legs weakness, thorax and back hyperalgesia. mRS was 2. CSF TRUST was 1:1. Serum TRUST was 1:32. T2-weighted MRI showed hyperintensity lesions in cervical and thoracic spinal cord, and enhancement in T1. She was diagnosed syphilitic myelitis. She started anti-treponemal antibiotics and prednisolone 60 mg for 7 days, and prednisolone was decreased 10mg per week. After 1 year, her symptoms
improved, only leaving numbness in the left leg. mRS was 1. Serum TRUST was 1:8. CSF TRUST was negative. There was no hyperintensity in the spinal cord. Patient 4, a 30-year-old male, presented syphilic rash and did not receive treatment. After 4 months, he presented with bilateral numbness of hips. mRS was 1. There were hyperintensity lesions in cervical and thoracic spinal cord, and enhancement in the superficial portion at C4-T1 (Fig. 1D, 1E). Serum TRUST was 1:4. CSF TRUST was 1:1. He was diagnosed syphilitic myelitis and started anti-treponemal antibiotics. After 6 months, his neurological symptoms disappeared. mRS was 0. Serum TRUST was 1:4. CSF TRUST was negative. There was no enhancement in spinal cord (Fig. 1F, and Tables 1e3). 3. Discussion and conclusions Up to now, the incidence rate of neurosyphilis in the untreated syphilis is 4%e10%, and 1.5% is developed to syphilitic myelitis [5]. Syphilitic myelitis can present with lower extremity weakness, sensory disturbance, and bladder or bowel dysfunction. Tashiro [6] firstly described the MRI characteristics of 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. 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 the changes are reversible [7]. In patient 2, hyperintensity was observed in cauda equina and round vertebra.
Fig. 1. A. T2-weighted MRI showing hyperintensity areas in the T1eT3 in Patient1. B. T2-weighted MRI showing atrophy in thoracic spinal cord in patient 1. C. enhanced image showing enhancement in cauda equina in patient 2. D. T2-weighted MRI showing high intensity areas in the C4-T2 in Patient 4. E. enhancement in the superficial portion of C4eT2 in Patient 4. F. T2-weighted MRI showing high intensity areas disappeared.
Please cite this article as: Wu Y, Wu W, Neurosyphilis presenting with myelitis-case series and literature review, J Infect Chemother, https:// doi.org/10.1016/j.jiac.2019.09.007
Y. Wu, W. Wu / J Infect Chemother xxx (xxxx) xxx
3
Table 1 The clinical manifestations and MRI of the syphilitic myelitis. Case Sex Age (years) Form of onset Duration 1
F
43
subacute
2
M
69
subacute
3
F
43
subacute
8 months
4
M
30
subacute
2 months
Clinical symptoms
20 months bilateral feet numbness and weakness, astriction, frequency of urinatiorunable to walk and numbness extended to the chest and urinary incontinence 2 years backache and chest distension. Symptoms got deteriorated, numbness and weakness in the legs until difficulty in walking, urinary incontinence.
chest and back pain, then numbness in the feet, and the numbness gradually appeared to her legs, to Saddle area weakness in her legs and hyperalgesia of thorax and back below bilateral articulatio coxae. bilateral hips numbness of gradually developed to the feet
Clinical signs
MRI
left limb weakness with a grade of 4. Bilateral positive babinski sign
T2 showed high intensity in T1-3 spinal cord
left limb weakness with a grade of 4 e5, right limb weakness with a grade of 4. Positive right babinski sign. Superficial sensory disturbance and diminished vibratory below the level of T6 bilateral limbs weakness with a grade of 5-.the feet vibratory (), Superficial sensory disturbance
T2 showed high intensity in T6-7, medullary cone and caudaequina
bilateral positive hoffmann signs, sense pain was impaired below T2.
T2 showed high intensity in cervical and thoracic spinal cord, enhancement in thoracic cord in T1
T2 showed high intensity in C4eT4, enhancement in the superficial portion of C4eT1
The duration is a time from appearing symptoms until diagnosed of neurosyphilis.
Table 2 The laboratory data and therapy of syphilitic myelitis. Case
TRUST (serum)
TRUST (csf)
TPPA (serum)
TPPA (csf)
Pressure
WBC (cells/mm3)
Pro (mg/dl)
OB
AQP-4
Therapy
1 2 3 4
1:32 1:16 1:32 1:8
1:4 1:1 1:2 1:1
þ þ þ þ
þ þ þ þ
150 120 170 130
7 8 88 7
111 138 59 53
e e e e
e e e e
Penicillin Penicillin Penicillin Penicillin
Table 3 The clinical symptoms, laboratory data and MRI after treatment. Case
Clinical symptoms
TRUST (serum)
TRUST (csf)
WBC
Pro
MRI
1 2 3 4
improvement deteriorated normal improvement
1:1 1:8 1:8 1:4
e e e e
4 1 4 4
25.6 106.7 34 42.9
thoracic spinal cord atrophy The thoracic spinal cord was normal, leaving lesions in the caudaequina cervical spinal cord atrophy T2 showed high intensity in T2eT4, enhancement in the superficial portion of C4eT1
We have not found any report about neurosyphilis involving cauda equina. The severe pain might be related to abnormal signals of nerve root. In patient 1, we discovered thoracic cord atrophy. The imaging manifestation has not been reported. We assumed the reason may be chronic inflammation and demyelination [8]. Lesions from neurosyphilis can be irreversible in the late stage, and spine atrophy is considered to be indicative of poor prognosis. The diagnosis of syphilitic myelitis mainly depends on clinical manifestations, MRI, and 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 and cryptococcal myelopathy. All patients were negative AQP-4. Hyperintensity of T2-weighted MRI was diminished or improved after antibiotic treatment. These can exclude NMOSD [9]. Corticosteroid should be given with all anti-treponemal antibiotics for neurological and cardiovascular syphilis because cardiovascular and neurological lesions may progress despite adequate treatment for syphilis [10]. However, there have been no clinical studies regarding the usefulness of corticosteroid therapy for syphilitic myelitis. Our cases suggested corticosteroids may be useful as an adjunctive treatment for syphilitic myelitis. Previous study have revealed that corticosteroids may be an important
adjunctive therapy for early neurosyphilis presenting with multiple cranial nerve palsies [11]. Moreover, there were a few reports of gumma treated by corticosteroids without antibiotics [12]. In my study, Patient 1 and patient 3 received antibiotics-corticosteroid treatment to improve neurological functions. Patient 2 only received corticosteroid therapy before penicillin therapy, suggesting that corticosteroid therapy was only an adjunctive therapy, and anti-treponemal antibiotics should be given as soon as possible. Syphilitic myelitis is an extremely rare disease. When encountering long-segment myelopathy, we should consider the possibility of syphilitic myelitis. All myelitis patients should undergo CSF examination as soon as possible when serum TRUST is positive. Prompt diagnosis and combined antibiotics-corticosteroid therapy may improve the neurological prognosis. Abbreviations AQP4 CSF MRI NMOSD OB TRUST TPPA HIV
Anti-aquaporin 4 Cerebrospinal fluid Magnetic resonance imaging Neuromyelitis optic spectrum disorder Oligoclonal bands toluidine red untreated serum test Treponema pallidum particle assay human immunodeficiency virus
Please cite this article as: Wu Y, Wu W, Neurosyphilis presenting with myelitis-case series and literature review, J Infect Chemother, https:// doi.org/10.1016/j.jiac.2019.09.007
4
Y. Wu, W. Wu / J Infect Chemother xxx (xxxx) xxx
VDRL RPR CNS LETM mRS
venereal disease research laboratory rapid plasma regain central nervous system longitudinally extensive transverse myelitis modified Rankin Scale
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Please cite this article as: Wu Y, Wu W, Neurosyphilis presenting with myelitis-case series and literature review, J Infect Chemother, https:// doi.org/10.1016/j.jiac.2019.09.007