Acute transverse myelitis in an immunocompetent patient: syphilis and cytomegalovirus—a case report

Introduction

Acute transverse myelitis (ATM) is a pathological heterogenous condition that causes acute or subacute spinal cord dysfunction. There are numerous causes which can be sub-categorised into para-infections, paraneoplastic, drug/toxin induced, systemic inflammatory conditions and demyelinating conditions (1). Diagnosis can be challenging as the presence of a normal magnetic resonance imaging (MRI) does not allude to exclusion of ATM. Spinal MRI findings can be non-specific and, in many cases, the MRI is normal (2). In a retrospective study by Zhou et al. on the comparison of prognosis of MRI positive versus negative in idiopathic ATM, approximately 40% of the cohort had normal spinal MRI on presentation at an average of 6 days from onset to MRI timing (3). Furthermore, clinical presentation may mimic other neurological disorders, for example Guillain-Barre syndrome (4).

We present a case of ATM in an immunocompetent a 56-year-old man who presented with clinical features of secondary syphilis with possible central nervous system (CNS) involvement. Serology also revealed cytomegalovirus (CMV) reactivation, which complicated the diagnostic process. This case highlights the diagnostic challenges of differentiating between syphilitic and CMV-associated ATM. We present this case in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-236/rc).

Case presentation

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

A 56-year-old man presented to the emergency department with a new painful desquamating, non-puritic palmer and plantar-surface rash. He also reported symmetrical polyarthropathy affecting the small joints of the hands and back pain with associated truncal sensory impairment. The patient presented to the emergency department at day 11 of his symptoms.

At day 1 onset of symptoms, the patient noticed palmer and plantar-surface desquamating non-puritic rash with associated swelling and stiffness of the small joints of the hands. At day 7 onset of symptoms, the patient reported new back pain with associated burning sensation within the truncal region before noticing impaired sensation. From day 7 to 19 onset of symptoms, the patient reported worsening truncal numbness which had extended superiorly and inferiorly compared to presentation to hospital. At day 19, the patient reported the spread of truncal sensory loss had plateaued and not deteriorated further.

Significant past medical history included previous shigella infection 6 months prior. The patient was on long-term use of pre-exposure prophylaxis (PrEP) (tenofovir disoproxil fumarate and emtricitabine) started 1-year ago as primary prophylaxis for human immunodeficiency virus (HIV) due to his history of promiscuous behaviour. At the time of diagnosis of acute shigella infection, a sexual health screen was sent including HIV and syphilis serology which were undetected. Social history revealed promiscuous homosexual behaviour. He denied any alcohol or illicit drug use.

Examination findings included symmetrical polyarthropathy affecting the small joints of the hands and a symmetrical yellow leathery rash affecting the palms and soles of the feet (see Figure 1). There was no abnormal focal neurology to note of both the cranial nerves and upper limbs. The lower limbs demonstrated preserved tone, power and reflexes with equivocal plantar reflexes. There was a symmetrical loss of sensation affecting dermatomes T5 to L1 of both light touch and pain sensory modalities. Tandem gait was normal. Romberg’s sign was negative and there was no pronator drift.

Figure 1 Desquamating palmer rash involving patient’s hands, consistent with secondary syphilis.

Admission cerebrospinal fluid (CSF) lumbar puncture (LP) results were as follows: glucose 3.2 mmol/L (normal range, 2.2–4.4 mmol/L), total protein 2.59 g/L (normal range, 0.15–0.45 g/L), white blood cells 17×10⁶/L (normal range, <5×10⁶/L), polymorphs 10% and lymphocytes 90%.

Oligoclonal bands were matched in both serum and CSF. CSF viral polymerase chain reaction (PCR) including herpes simplex virus (HSV) type 1 and 2, varicella zoster virus and parechovirus were negative.

MRI head and whole spine with gadolinium did not demonstrate any structural abnormality (Figures 2-7).

Figure 2 MRI head coronal image T2 sequence demonstrating no structural abnormality acquired in June 2024. MRI, magnetic resonance imaging.

Figure 3 MRI head coronal image T2 sequence at the level of the optic nerves demonstrating no structural abnormality acquired in June 2024. MRI, magnetic resonance imaging.

Figure 4 MRI cervical spine T1-post contrast demonstrating no structural abnormality acquired in June 2024. MRI, magnetic resonance imaging.

Figure 5 MRI cervical spine T2 sequence demonstrating no structural abnormality acquired in June 2024. MRI, magnetic resonance imaging.

Figure 6 MRI thoracic spine T1 post contrast demonstrating no structural abnormality acquired in June 2024. MRI, magnetic resonance imaging.

Figure 7 MRI thoracic spine T2 sequence demonstrating no structural abnormality acquired in June 2024. MRI, magnetic resonance imaging.

Subsequent neurophysiology studies including nerve conduction studies and electromyography studies were performed and overall, showed no evidence of demyelination of the motor nerves in the lower limbs. Sensory potentials were within normal limits.

Further investigations were performed to investigate the underlying aetiology of ATM. A rheumatological panel consisting of rheumatoid factor, anti-cyclic citrullinated peptide antibodies, antinuclear antibody (ANA), anti-double stranded DNA (anti-DsDNA), antineutrophil cytoplasmic antibodies (ANCAs), immunoglobulins, complement levels, human leukocyte antigen (HLA) B27 and uric acid were all negative. Thyroid function tests were normal. Vitamin B12 and methymelonic acid were within normal range. Lead levels, B2-microglobulin and homocysteine were within normal limits. HbA1C was 38 mmol/moL. Immunoglobulins both immunoglobulin A (IgA) and immunoglobulin M (IgM) were—IgA 2.65 g/L (normal range, 0.8–4.0 g/L) and IgM 1.97 g/L (normal range, 0.2–2.0 g/L). Immunoglobulin G (IgG) was slightly elevated at 21.4 g/L (normal range, 6.0–16.0 g/L) but total protein was normal 73 g/L (normal range, 60–80 g/L).

Sexual health screen was also performed. Nucleic acid amplification tests (NAATs) for chlamydia were positive but negative for Neisseria gonorrhoea. Treponema pallidum haemagglutination assay (TPHA) was positive >1:80 and rapid plasma reagin (RPR) 1:128. HIV screen was negative. Cytomegalovirus (CMV) serology demonstrated both positive IgM and IgG. CMV IgM was 4.28 above sample cut off and CMV IgG >250 AU/mL.

After the results of both syphilis and CMV serology returned positive, we attempted to test CSF for Venereal Disease Research Laboratory (VDRL) and CMV. Unfortunately, the laboratory was unable to process due to insufficient sample.

Given the results, the patient received treatment for his syphilis which included 14 days of intravenous ceftriaxone and a 3-day course of high-dose prednisolone to prevent a Jarisch-Herxheimer reaction. Chlamydia was treated with a 10-day course of doxycycline. During his hospital stay, the physiotherapy team worked with him to improve mobility.

At discharge, the rash and arthropathy had predominantly resolved. The central back pain had improved to a more tolerable level, but his sensory truncal loss did not improve.

We arranged follow-up 4 months post discharge for both clinical review and repeat lumbar puncture. Referral to genito-urinary medicine team was made prior to discharge.

At the 4-month follow-up, the patient reported ongoing truncal sensory impairment with slight improvement despite completing treatment for syphilis. Examination findings demonstrated T5–L1 sensory impairment in both pain and light touch sensory modalities but subjectively, the patient reported slight improvement compared to presentation.

Repeat lumbar puncture CSF results at 4-month follow-up were as follows: glucose 2.8 mmol/L (normal range, 2.2–4.4 mmol/L), total protein 0.61 g/L (normal range, 0.15–0.45 g/L) and white blood cells 1×10⁶/L (normal range, <5×10⁶/L). CSF CMV DNA quantification and CSF VDRL PCR were negative.

Serological TPPA titre >1:80 and RPR titre 1:8. CMV IgM remained positive. CMV IgM 3.54 above sample cut off and CMV IgG remained >250 AU/mL.

Given his ongoing symptoms, he was subsequently referred onwards to infectious disease team for consideration of anti-viral treatment. However, 8 months from onset of symptoms, the patient reported resolution of truncal sensory loss. He did not receive any anti-viral treatment (Figure 8).

Figure 8 Timeline describing the symptom onset, presentation to hospital and recovery. ED, emergency department; HIV, human immunodeficiency virus; LP, lumbar puncture; MRI, magnetic resonance imaging.

Discussion

ATM is a rare and rapid onset condition that can affect any part of the spinal cord and therefore symptoms that arise coincide with the affected location. Most commonly, ATM affects the thoracic spinal cord (1).

The clinical findings in this case suggest a diagnosis of ATM. Dermatome of segments T5–L1 were affected. Corresponding MRI head and whole spine excluded compressive or demyelinating aetiology. The combination of normal MRI findings, abnormal CSF findings including both elevated protein level and lymphocytosis and presentation within 21 days of symptom onset all fulfil the proposed diagnostic criteria of ATM (5). With a wide array of causes of ATM, we carried out a full panel of investigations that largely returned normal findings except for serological positive CMV IgM and IgG antibodies and syphilis serology.

CMV acute infection in immunocompetent individuals usually manifests as benign and self-limiting condition mimicking mononucleosis-like syndrome. Its seroprevelance in both immunocompetent and immunocompromised population ranges from 60% to 100% (6). The presence of both serological CMV IgM and IgG suggests evidence of current acute CMV infection and previous primary CMV infection. This could be in the form of CMV reactivation or an acute infection of a new strain of CMV (7). CMV CNS disorders in immunocompetent individuals have been documented in literature and can present as myelitis. Although rare, it is more prevalent in severely immunocompromised patients for example in patients with advance HIV infection or those who have previously undergone bone marrow or solid organ transplantation (6,8).

Diagnosis of CMV myelitis is challenging as the absence of CSF CMV DNA is not a test of exclusion. In the majority of cases, CMV DNA is not detected in the CSF in those with suspected CMV myelitis. In a case report by Merchan-Del Hierro et al., the subject had absent CSF CMV DNA but positive CMV serology IgM and MRI findings demonstrated spinal cord swelling and signal changes (9). This is further supported by a literature search performed by Fux et al. In their case report, they reviewed eight published cases of CMV-associated ATM in immunocompetent patients. Approximately 50% of the cases with available information of MRI scans demonstrated normal spinal cords. Of those who had CSF CMV PCR testing, none had positive findings. The absence of MRI finding or positive CSF CMV PCR does not exclude CMV myelitis and suggests an immune-mediated pathophysiology rather than direct viral induced neuronal damage (10).

Treatment of CMV-related CNS disease in immunocompetent individuals is rather conflicting as there are not current available randomised-control trials that support the use of antivirals. Moreover, CMV in immunocompetent individuals is a self-limiting disease and therefore symptom resolution with antivirals may be a reflection of this rather than success of the treatment itself (6). The current treatment consensus is if the prognosis of severe CMV infection is poor then the use of intravenous antivirals should be considered (11).

The prevalence of syphilis is rising and approximately 30% of patients who have early syphilis will have evidence of neuroinvasion. In its early stages, neurosyphilis can be asymptomatic or symptomatic. In those who are asymptomatic, the majority will have resolution of CSF abnormalities regardless of intervention with treatment. Early symptomatic neurosyphilis predominantly manifests as acute meningitis, most commonly affecting the basilar region and usually presents within 12 months from onset of acute infection. Tertiary neurosyphilis classically presents after 12 months from acute infection and can manifest in a variety of different forms. Meningovascular complications of neurosyphilis occur 5–12 years post infection and can present for example as cerebral stroke or meningomyelitis. Neurosyphilis recovery prognosis post treatment is not clearly documented within the literature and resolution of symptoms is hard to predict and may not occur (12).

Diagnosing neurosyphilis remains challenging because there is no single test that can be used to diagnose neurosyphilis. Current Centers for Disease Control and Prevention guidelines suggest a diagnosis of neurosyphilis is defined as a combination of CSF abnormalities including pleocytosis, elevated protein level or reactive VDRL in the presence of abnormal serological syphilis serology with abnormal neurological signs and symptoms. VDRL CSF testing is most commonly used when testing for the presence of syphilis in the CNS in clinical practice due to its high specificity (78–90%) in symptomatic neurosyphilis patients. However, its sensitivity is limited ranging from 48% to 88% in symptomatic neurosyphilis patients (13).

Syphilitic myelitis is a rare manifestation of symptomatic neurosyphilis, representing approximately only 3% of cases of all neurosyphilis cases. Consequently, there is limited literature available and therefore syphilis myelitis remains a challenging diagnosis. Generally speaking, the consensus is that a diagnosis of syphilis myelitis is achieved by abnormalities seen on CSF that reflect ATM, the presence of CSF VDRL and MRI abnormalities suggesting signs of longitudinal extensive myelopathy or “flip flop sign”. In a literature search by Yuan et al., 20 cases of syphilis myelitis were reviewed and 80% of the cases demonstrated abnormalities on spinal MRI T2 sequence with gadolinium enhancement. These abnormalities included spinal cord swelling or longitudinal extensive T2 hyperintensities. In 85% of cases, corresponding CSF results showed positive VDRL or TPHA (14).

The underlying aetiology of our patient’s ATM is not completely certain. Clinical history and presentation highly suggest a diagnosis of syphilis and neurosyphilis as the most plausible diagnosis. However, further evaluation revealed evidence of active CMV infection, which complicated the determination of the underlying cause. Based on the evidence presented, CMV is favoured as the most likely cause of this myelitis, although definitive proof is lacking.

Conclusions

This case highlights the diagnostic complexity of ATM in immunocompetent patients. Although neurosyphilis was initially suspected, the absence of MRI abnormalities and the persistence of CMV IgM and IgG positivity favour CMV reactivation or infection of a new strain as the underlying cause. Clinicians should maintain a broad differential when evaluating ATM, recognizing that CMV myelitis can occur even with negative CSF PCR and normal MRI findings.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-236/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-236/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-236/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Beh SC, Greenberg BM, Frohman T, et al. Transverse myelitis. Neurol Clin 2013;31:79-138. [Crossref] [PubMed]
2. Goh C, Desmond PM, Phal PM. MRI in transverse myelitis. J Magn Reson Imaging 2014;40:1267-79. [Crossref] [PubMed]
3. Zhou Y, Chen Q, Gan W, et al. Comparison between MRI-negative and positive results and the predictors for a poor prognosis in patients with idiopathic acute transverse myelitis. BMC Neurol 2024;24:226. [Crossref] [PubMed]
4. Simone CG, Emmady PD. Transverse Myelitis. Treasure Island, FL, USA: StatPearls Publishing; 2022.
5. Proposed diagnostic criteria and nosology of acute transverse myelitis. Neurology 2002;59:499-505. [Crossref] [PubMed]
6. Rafailidis PI, Mourtzoukou EG, Varbobitis IC, et al. Severe cytomegalovirus infection in apparently immunocompetent patients: a systematic review. Virol J 2008;5:47. [Crossref] [PubMed]
7. Styczynski J. Who Is the Patient at Risk of CMV Recurrence: A Review of the Current Scientific Evidence with a Focus on Hematopoietic Cell Transplantation. Infect Dis Ther 2018;7:1-16. [Crossref] [PubMed]
8. Maschke M, Kastrup O, Diener HC. CNS manifestations of cytomegalovirus infections: diagnosis and treatment. CNS Drugs 2002;16:303-15. [Crossref] [PubMed]
9. Merchan-Del Hierro X, Halalau A. Cytomegalovirus-related transverse myelitis in an immunocompetent host: a subacute onset of an immune-mediated disease? BMJ Case Rep 2017;2017:bcr2017220563. [Crossref] [PubMed]
10. Fux CA, Pfister S, Nohl F, et al. Cytomegalovirus-associated acute transverse myelitis in immunocompetent adults. Clin Microbiol Infect 2003;9:1187-90. [Crossref] [PubMed]
11. Tan BH. Cytomegalovirus Treatment. Curr Treat Options Infect Dis 2014;6:256-70. [Crossref] [PubMed]
12. Hamill MM, Ghanem KG, Tuddenham S. State-of-the-Art Review: Neurosyphilis. Clin Infect Dis 2024;78:e57-68. [Crossref] [PubMed]
13. Center for Disease Control and Prevention (CDC). Syphilis. Sexually Transmitted Infections Treatment Guidelines. 2021 [cited 30 March, 2025]. Available online: https://www.cdc.gov/std/treatment-guidelines/syphilis.htm#print
14. Yuan JL, Wang WX, Hu WL. Clinical features of syphilitic myelitis with longitudinally extensive myelopathy on spinal magnetic resonance imaging. World J Clin Cases 2019;7:1282-90. [Crossref] [PubMed]