To assess the utility of glial antibody testing and metagenomic next-generation sequencing (mNGS) of serum and cerebrospinal fluid (CSF) in the diagnostic work-up of myelopathy in Ugandan patients.

Non-traumatic myelopathy etiologies have not been well characterized in Sub-Saharan Africa.

Adults presenting with clinical features localizing to the spinal cord were prospectively enrolled in a research study at Mulago and Kiruddu National Referral Hospitals in Kampala, Uganda from 2018-2022. 1.5 Tesla magnetic resonance imaging (MRI) was performed on the spinal cord. Serum and CSF were tested for antibodies to aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) by live cell-based flow cytometry at Mayo Clinic. mNGS was performed on RNA extracted from CSF at UCSF.

134 patients were enrolled. The median age was 32 years (range, 18-85) with 55% male and 25% HIV positive. Most (n=88 [66%]) had intradural abnormalities on MRI. Ten participants had MOG-IgG detected with a median MOG-IgG-binding-index of 2.53 (range, 1.22-3.8), of whom 8 had intramedullary lesions and 2 a normal MRIs. AQP4-IgG was detected in 10 patients with median AQP4-IgG-binding-index 20.33 (range, 2.25-63.51). Six had intramedullary lesions and four patients with normal MRIs. CSF mNGS detected Schistosoma mansoni in 10 patients and varicella-zoster virus in one patient and all 11 had MRI abnormalities. Cytomegalovirus (CMV) sequences were detected in 35 patients, though in only 2 HIV-infected patients was the CMV copy number likely high enough to be associated with the clinical presentation. Vitamin B12 deficiency was diagnosed in 5 patients.

AQP4/MOG-IgG and mNGS identified the underlying etiology in a quarter of the non-traumatic myelopathy cohort, with AQP4-IgG positive NMOSD and MOGAD accounting for up to 15% of cases. S. mansoni, a treatable parasitic infection, was the most common infectious etiology. Making these studies available to developing countries should be a priority.