Evaluation of clinical outcomes in LETM.

Longitudinally extensive transverse myelitis (LETM) is typically defined as spinal cord inflammation that spans 3 or more vertebral segments on MRI.  It is a prototypical manifestation of neuromyelitis optica spectrum disorder (NMOSD) but is also seen in myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and much less commonly multiple sclerosis. In some cases, despite extensive investigation, a definitive diagnosis cannot be reached, a condition referred to as double seronegative LETM (dsLETM).

Cohort study of LETM cases reviewed in NMO UK Highly Specialised Service at the Walton Centre NHS Foundation Trust between Jan 2008-March 2022.  Clinical presentation, radiological characteristics, aquaporin-4 antibodies (AQP4-IgG) and MOG antibodies, relapses, treatment, and EDSS at follow-up were extracted from case records.  

LETM=93 cases were identified; NMOSD=41 (AQP4-IgG positive; 88%), dsLETM=29, MOGAD=17, others=6. The median onset age was 46 (15-85) yrs with a median follow-up of 46 (1-144) months.  EDSS at nadir was similar between subgroups (NMOSD; 7, MOGAD; 7.5, dsLETM; 6.7, p>0.05) but patients with dsLETM were less likely to relapse (dsLETM; 21% vs. NMOSD; 56% vs. MOGAD; 29%, p=0.008). Long term immunosuppression was used in NMOSD (100%), MOGAD (76%) and dsLETM (34%) and was associated with a reduction in median annualised relapse rate (NMOSD; 1.65 to 0.09, MOGAD; 0.75 to 0.07, and dsLETM; 1 to 0.11). Although EDSS scores at last review were higher in NMOSD than MOGAD (6 vs. 4; p=0.018) and dsLETM (6 vs 4.5; p=0.04), dsLETM patients still reached a significant disability (EDSS>6) in 35% of cases. 

Patients with dsLETM relapsed less as compared to NMOSD and MOGAD and immunosuppression reduced the risk further. Although last EDSS was lower in dsLETM as compared to NMOSD, a third of patients still suffered from significant disability.