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Neuromyelitis Spectrum Disorder (NMOSD)

Summary

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  • Autoimmune inflammatory disorder primarily affecting optic nerves and spinal cord, associated with aquaporin-4 (AQP4) antibodies in most cases
  • Presents with severe optic neuritis, longitudinally extensive transverse myelitis, and area postrema syndrome
  • MRI shows longitudinally extensive spinal cord lesions (≥3 vertebral segments) and bilateral optic nerve enhancement

Pathophysiology

  • Autoimmune astrocytopathy mediated by IgG antibodies against aquaporin-4 (AQP4) water channels
    • AQP4 highly expressed on astrocytic foot processes at blood-brain barrier
    • Antibody binding leads to complement activation and astrocyte destruction
    • Secondary demyelination and neuronal injury
  • Seronegative cases (AQP4-IgG negative) may have:
    • Myelin oligodendrocyte glycoprotein (MOG) antibodies
    • Unknown antibodies or cellular immunity mechanisms
  • Preferentially affects areas with high AQP4 expression:
    • Periventricular regions (especially area postrema)
    • Optic nerves and chiasm
    • Central spinal cord gray matter

Demographics

  • Female predominance (9:1 ratio in AQP4-positive cases)
  • Mean age of onset: 35-40 years (later than multiple sclerosis)
  • Higher prevalence in Asian and African populations
  • Associated conditions:
    • Autoimmune disorders (thyroiditis, myasthenia gravis, SLE)
    • Occurs in 3-5% of patients with systemic lupus erythematosus
  • Paediatric cases account for 3-5% of all NMOSD

Diagnosis

  • 2015 International Panel Diagnostic Criteria:
    • Core clinical characteristics (at least one required):
    • Optic neuritis
    • Acute myelitis
    • Area postrema syndrome (intractable hiccups/nausea/vomiting)
    • Acute brainstem syndrome
    • Symptomatic narcolepsy or acute diencephalic syndrome
    • Symptomatic cerebral syndrome
  • Laboratory findings:
    • AQP4-IgG seropositivity (70-80% of cases)
    • MOG-IgG positive in some seronegative cases
    • CSF pleocytosis (>50 WBC/μL in 35% during attacks)
    • Elevated CSF protein
    • Oligoclonal bands typically absent (unlike MS)
  • Clinical presentation:
    • Severe bilateral or unilateral optic neuritis with poor recovery
    • Transverse myelitis with paraparesis/quadriparesis
    • Intractable hiccups and vomiting (area postrema syndrome)

Imaging

  • Spinal Cord MRI:
    • T2: Longitudinally extensive hyperintense lesions spanning ≥3 contiguous vertebral segments
    • Central cord predominance ("central gray matter pattern")
    • Cervical and thoracic cord most commonly affected
    • T1: Hypointense lesions in acute phase, may show cord swelling
    • T1+C: Variable enhancement, often patchy or ring-like
    • Chronic changes: Cord atrophy and central cavitation
  • Brain MRI:
    • T2/FLAIR: Periependymal lesions around third and fourth ventricles
    • Area postrema lesions (dorsal medulla)
    • Hypothalamic and thalamic lesions
    • Corpus callosum lesions (unlike MS, follow ependymal surface)
    • T1+C: Enhancement of area postrema and periependymal regions during acute attacks
    • Cloud-like enhancement pattern in some cases
  • Optic Nerve MRI:
    • T2: Hyperintense signal in affected optic nerves
    • Often bilateral and extensive (>50% of nerve length)
    • Involvement of optic chiasm common
    • T1+C: Enhancement of optic nerves, often extensive
    • STIR: Superior for detecting optic nerve lesions
  • Advanced Imaging:

Differential diagnosis

Differential diagnosis Differentiating feature
Multiple sclerosis (MS) Short (<3 vertebral segments) eccentric cord lesion; periventricular ovoid brain lesions; calloso-septal interface
Acute disseminated encephalomyelitis (ADEM) Multifocal bilateral white matter and basal ganglia brain lesions; no area postrema involvement
Systemic lupus erythematosus (SLE) Small vessel ischaemic white matter lesions without longitudinally extensive cord lesion; no area postrema involvement
Sarcoidosis Cranial nerve and leptomeningeal enhancement; hypothalamic/infundibular thickening; subpial linear cord enhancement
CNS vasculitis Vessel wall enhancement on high-resolution MRI; cortical and subcortical infarcts; abnormal angiography
Infectious myelitis Cord expansion and enhancement without longitudinally extensive pattern; epidural or parameningeal infection
Spinal cord tumour Expansile intramedullary mass with contrast enhancement; haemosiderin cap (ependymoma); no area postrema lesion
Vitamin B12 deficiency Posterior and lateral column T2 signal ("inverted V" sign); no area postrema involvement
Copper deficiency Posterior column predominant cord T2 signal; identical to B12 deficiency on imaging

panels-1

  • A 45-year-old patient presented with lower limb weakness and sphincter disturbance.
  • MRI showed a longitudinally extensive lower thoracic cord lesion without contrast enhancement extending 7 vertebral levels.
  • There were no intracranial lesions.
  • CSF tested positive for aquaporin 4 antibodies.