Chronic pain despite lower lesion burden in double-seronegative longitudinally extensive transverse myelitis

Chronic pain is a frequent complication of longitudinally extensive transverse myelitis (LETM). In neuromyelitis optica spectrum disorder-associated transverse myelitis (NMOSD-TM), pain has been largely attributed to AQP4-IgG-mediated inflammation. However, pain burden in double-seronegative LETM (DSN-LETM) remains poorly characterized.

In this prospective study, patients with LETM (≥3 vertebral segments) in remission were enrolled and classified as DSN-LETM (negative for anti-aquaporin-4 and anti-MOG antibodies) or seropositive NMOSD-TM. Pain was assessed using PainDETECT and the Brief Pain Inventory. Health-related quality of life (HRQoL) was evaluated using EuroQoL-5D at baseline and 6-12 months.

Fifty-four patients were included (DSN-LETM, n = 9; NMOSD-TM, n = 45; median age 57 years). Compared with NMOSD-TM, DSN-LETM had shorter cumulative spinal cord lesion length and less cervical involvement, indicating lower structural lesion burden. Despite this, all DSN-LETM patients reported chronic pain (100%), compared with 87% in NMOSD-TM. Numbness was more prominent in DSN-LETM. In NMOSD-TM, pain severity was significantly associated with clinical disability and lesion burden, whereas no such associations were observed in DSN-LETM. Greater pain severity was associated with poorer HRQoL in both groups and remained stable over a median 7-month follow-up.

Chronic pain in DSN-LETM is substantial and persistent despite limited lesion burden, highlighting a dissociation between structural inflammatory burden and pain severity. These findings suggest that pain in DSN-LETM may not be adequately captured by conventional measures of lesion burden, underscoring the importance of proactive pain assessment and management.