A 14-year-old girl developed aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD) following Mycoplasma pneumoniae infection. She initially presented with fever, vomiting, seizures and respiratory failure. Brain magnetic resonance imaging revealed isolated splenial lesions. However, she subsequently developed extensive lesions in the hypothalamus, brainstem and spinal cord. Serum and cerebrospinal fluid tested positive for anti-AQP4 antibodies. She was diagnosed with AQP4-IgG-positive NMOSD and treated with corticosteroids, leading to clinical stabilisation. This case provides evidence that M. pneumoniae infection may trigger AQP4-antibody-positive NMOSD, possibly through molecular mimicry. Clinicians should be aware of this potential association, and further research is needed to understand the underlying mechanisms.
Supplementary Information: The online version contains supplementary material available at 10.1186/s12887-025-06155-w.
Keywords: Mycoplasma pneumoniae infection; Aquaporin-4 antibody; Autoimmune disease; Neuromyelitis optica spectrum disorders; Reversible splenial lesion syndrome.