# The Mystery of a Negative Workup: A Diagnostic Dilemma in Seronegative Immune-Mediated Transverse Myelitis

**Authors:** Niyas Khalid Ottu Para, Uvashree Shrinivas, Fareeda Udyavar Karoda

PMC · DOI: 10.7759/cureus.103440 · Cureus · 2026-02-11

## TL;DR

A 44-year-old man with symptoms of spinal inflammation showed no positive antibody tests but improved with steroid treatment, highlighting the challenges in diagnosing seronegative immune-mediated transverse myelitis.

## Contribution

The paper presents a case emphasizing the diagnostic challenges and management of seronegative immune-mediated transverse myelitis through systematic exclusion and treatment response.

## Key findings

- The patient showed clinical improvement after high-dose intravenous methylprednisolone despite seronegative test results.
- Diagnostic evaluation ruled out infectious, autoimmune, granulomatous, and paraneoplastic causes in the case of transverse myelitis.
- The case underscores the importance of longitudinal assessment and therapeutic responsiveness in managing seronegative immune-mediated TM.

## Abstract

Transverse myelitis (TM) is an acquired inflammatory disorder of the spinal cord with a heterogeneous aetiology that includes demyelinating, autoimmune, infectious, granulomatous, and paraneoplastic causes. Although advances in antibody testing, particularly aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG), have refined the classification of many cases, a significant proportion remain seronegative, presenting diagnostic and therapeutic challenges.

We report the case of a 44-year-old man who presented with progressive fatigue, significant weight loss, lower abdominal numbness, urinary urgency, and intermittent blurred vision. Magnetic resonance imaging of the thoracic spine demonstrated an intramedullary T2 hyperintense lesion at the T10-T11 level with patchy gadolinium enhancement, consistent with inflammatory myelitis. An extensive diagnostic evaluation excluded infectious, systemic autoimmune, granulomatous, endocrine, demyelinating, and paraneoplastic causes. The patient showed marked clinical improvement following high-dose intravenous methylprednisolone, with resolution of sensory and autonomic symptoms and stabilisation of weight, while mild fluctuating fatigue persisted.

This case highlights the diagnostic grey zone of seronegative immune-mediated TM and underscores the importance of systematic exclusion, longitudinal assessment, and therapeutic responsiveness in establishing diagnosis and guiding management.

## Linked entities

- **Proteins:** AQP4 (aquaporin 4)
- **Chemicals:** methylprednisolone (PubChem CID 6741)
- **Diseases:** transverse myelitis (MONDO:0021553)

## Full-text entities

- **Genes:** AQP4 (aquaporin 4) [NCBI Gene 361] {aka MIWC, MLC4, WCH4, hAQP4}
- **Diseases:** inflammatory myelitis (MESH:D009187), TM (MESH:D009188), fatigue (MESH:D005221), inflammatory disorder of the spinal cord (MESH:D013118), granulomatous (MESH:D013968), numbness (MESH:D006987), paraneoplastic (MESH:D010257), autoimmune (MESH:D001327), weight loss (MESH:D015431), blurred (MESH:D014786), demyelinating (MESH:D003711)
- **Chemicals:** methylprednisolone (MESH:D008775)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

11 references — full list in the complete paper: https://tomesphere.com/paper/PMC12989039/full.md

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Source: https://tomesphere.com/paper/PMC12989039