Etiologies of Myelopathy in Uganda Based on Neuroimaging, Autoantibodies, and Next Generation Sequencing
Kisekka Musubire1, Kristoffer Leon2, Eoin Flanagan3, David Meya4, David Boulware5, Paul Bohjanen6, Patrick Cras7, Barbara Willekens8, Sean Pittock9, Michael Wilson10
1Mulago National Referal Hospital, 2University of California, San Francisco, 3Mayo Clinic, 4Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda, 5University of Minnesota, 6University of Rochester Medical Center, 7University of Antwerp, 8Antwerp University Hospital, 9Mayo Clinic Dept of Neuro, 10University of California San Francisco
Objective:

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.

Background:

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

Design/Methods:

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.

Results:

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.

Conclusions:

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.

10.1212/WNL.0000000000206108