Case Study: Rare Coexistence of NMO Spectrum Disorder & Ankylosing Spondylitis in Indian Male

Introduction

Neuromyelitis optica spectrum disorder (NMOSD) and ankylosing spondylitis (AS) are two distinct autoimmune conditions, rarely seen together in the same patient. NMOSD is an autoimmune demyelinating disorder of the central nervous system (CNS), primarily affecting the optic nerves and spinal cord. The hallmark of NMOSD is the presence of anti-aquaporin-4 (AQP4) antibodies, which target astrocytes, leading to inflammation and demyelination. On the other hand, AS is an immune-mediated disease classified under axial spondyloarthropathies, primarily affecting the axial skeleton and peripheral joints, with a strong association with the HLA-B27 antigen. Although coexisting autoimmune conditions are common in NMOSD patients, the concurrent existence of NMOSD and AS is an uncommon phenomenon, with only a handful of cases documented globally.

In this case study, we present a 35-year-old Indian man with undiagnosed progressive AS, who presented with acute-onset longitudinally extensive transverse myelitis (LETM), a clinical subset of NMOSD. His case highlights the importance of early diagnosis and appropriate management of both conditions to prevent lifelong disabilities.

Case Presentation

A 35-year-old man from a rural area in India came with the complaint of tingling, numbness, and progressive weakness of the lower limbs, which mainly affected one side and was present for 10 days. He had associated acute urinary retention and catheterization was performed. This patient was bedridden by the end of a week when his weakness progressed. Following catheter removal, he had urinary incontinence, urgency, and increased micturitions.

He denied any history of trauma, fever, recent vaccination, or radicular pain but had dull-aching pain over the gluteal region and lower back on both sides for the past 8 months. The pain lasted at least an hour after waking and improved with movement but was made worse with periods of prolonged inactivity. It woke him at night almost invariably to relieve the discomfort by walking about.

With these symptoms, the patient still had not sought to see any trained medical practitioner. Instead, he took over-the-counter pain medication as prescribed to him by indigenous medical practitioners. According to his indigenous medical practitioners, the patient's pain resulted from overexertion while engaging in agricultural work.

Examination and Diagnosis

The patient presented with asymmetric spastic paraparesis, predominantly on the right side, following a history and physical examination. He also had an upper motor neuron-type bladder symptom along with preserved posterior column sensations. There was no abnormal sensory level and his neuro-ophthalmological examination was normal. His cerebellar functions were intact though he had paretic lower limbs.

The patient was admitted with the history and physical examination pointing towards an acute onset non-compressive myelopathy with anterior central cord involvement. After having a proper history and examination, the patient underwent further investigations to determine etiology.

Investigations

Laboratory tests revealed normal results for liver, kidney, and thyroid function, plasma glucose, and electrolytes. However, his erythrocyte sedimentation rate (ESR) was elevated (66 mm in the first hour). A spinal cord MRI showed a demyelinating lesion from the C5 to D4 levels, characteristic of LETM. Additionally, an MRI of the sacroiliac joints revealed bilateral sacroiliitis, supporting a diagnosis of axial spondyloarthropathy.

Serum and cerebrospinal fluid (CSF) analysis revealed positive anti-AQP4 antibodies, confirming NMOSD. The CSF also showed lymphocytic pleocytosis and elevated protein levels. Other autoimmune markers, such as anti-nuclear antibody (ANA), anti-myelin oligodendrocyte glycoprotein (MOG) antibodies, and rheumatoid factor, were negative. HLA-B27 testing was positive, confirming the presence of AS.

Final Diagnosis

The patient was diagnosed with AQP4-positive NMOSD coexisting with AS. This rare combination of autoimmune disorders was further complicated by the patient's delayed diagnosis and mismanagement by indigenous medical practitioners.

Treatment and Management

The patient was started on pulse intravenous methylprednisolone therapy (1 g/day for 5 days), resulting in significant improvement in his lower limb strength. To prevent relapses, cyclical rituximab therapy was initiated. Rituximab, a monoclonal antibody targeting CD20-positive B-cells, is commonly used to treat NMOSD by reducing the production of AQP4 antibodies.

Over 6 months, the patient's neurological function improved significantly, with no residual deficits except for mild paresthesias. Follow-up MRI scans showed no new lesions, and his Ankylosing Spondylitis Disease Activity Score (ASDAS) indicated a marked reduction in disease severity.

Discussion

This case underlines the rare coexistence of NMOSD and AS, two autoimmune disorders with very distinct pathogenic mechanisms. NMOSD is mainly an antibody-driven pathology, specifically AQP4 antibodies targeting astrocytes, through complement-mediated damage and demyelination. In sharp contrast, AS is primarily T-cell-driven inflammation with a much less relevant role of B-cells. Although theoretically quite distinct, there is growing evidence of overlap in immune pathways, especially in the coexistence of NMOSD with AS.

Let's take another look at this patient. The clinical presentation of this patient is quite typical for NMOSD, but the long history of low back pain and sacroiliitis best describes AS. The patient could be a poster boy for the shared immune mechanism of both these diseases because the patient responds so well to immunomodulatory treatment.

Conclusion

This case illustrates the importance of a diagnosis that allows for the recognition of the potential coexistence of autoimmune disorders in patients with complex neurological presentations. Early diagnosis and management might lead to avoiding permanent disability, as the patient's condition has improved significantly with timely treatment.

However, there is a need to further research the underlying pathophysiological mechanisms linking NMOSD and AS in addition to long-term follow-ups of patients with these diseases. Another important aspect of this case is related to raising awareness of NMOSD and AS in rural areas, where access to medical professionals with appropriate training is already limited.

References

1. Wingerchuk DM, et al. Neuromyelitis optica spectrum disorders: Updated diagnostic criteria. Neurology.

2. Broadley SA, et al. Neuromyelitis optica in patients with aquaporin-4 antibodies: Implications for clinical practice. J Neurol Neurosurg Psychiatry.

3. Braun J, Sieper J. Ankylosing spondylitis. Lancet.

4. Jarius S, et al. The role of aquaporin-4 antibodies in the pathogenesis of NMOSD. Curr Opin Neurol.

5. Van Der Heijde D, et al. ASDAS: A disease activity score for ankylosing spondylitis. Ann Rheum Dis.

6. Montalban X, et al. Multiple sclerosis and other demyelinating diseases. Neurology.

7. Kitley J, et al. Coexistence of NMOSD with other autoimmune conditions. Neurology.

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