Chronic inflammation is frequent and leads to neurodegeneration in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSDs) regardless of disease stage, according to the results of a new study published in Brain.

“Our findings should make the scientific community pause on the way inflammation and treatment response are assessed in clinical practice and how we approach therapeutic intervention, especially in longstanding and end-stage disease,” the researchers said.

Inflammatory demyelinating diseases such as MS and NMOSD often affect the anterior optic pathway and lead to optic neuritis. But in most cases, optical coherence tomography shows progressive neuroretinal thinning without optic neuritis. It is not clear why this happens.


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Here, a team of researchers led by Gabriele C. DeLuca MD, PhD, FRCPath, FAAN, from the Nuffield Department of Clinical Neurosciences at the University of Oxford in England analyzed postmortem tissue samples of optic nerves, chiasms, and optic tracts of patients with MS, NMOSD, and acute disseminated encephalomyelitis as well as nonneurological controls. 

Read more about NMOSD etiology

The researchers assessed the distribution and extent of markers of myelin, inflammation, acute axonal injury, and astrocytes along the anterior optic pathway. The results showed that in MS, demyelination was present in 82.8% of cases. Of these, 75% showed activity.

In nondemyelinated regions, microglia/macrophage and lymphocyte inflammation were frequent. The acute axonal injury was seen in a little less than half (41.4%) of patients and correlated with the extent of inflammation. In the case of optic nerves that were most severely affected, an anteroposterior gradient of anterior optic pathway involvement was seen. In these cases, the optic nerves were most severely affected by inflammation and acute axonal injury.

In the case of NMOSD, patients who had a history of optic neuritis had extensive demyelination. They also lost aquaporin-4 reactivity. On the contrary, patients without prior optic neuritis did not have demyelination. Instead, they had diffuse microglial/macrophage, and T and B-cell inflammation in both parenchymal and meningeal compartments. The majority (75%) of cases had acute axonal injuries.

The researchers concluded that chronic inflammation and subsequent neurodegeneration along the optic pathway could partly explain the progressive neuroretinal changes that are seen in optic coherence tomography studies.

Reference

Pisa M, Pansieri J, Yee S, et al. Anterior optic pathway pathology in CNS demyelinating diseases. Brain. 2022;3. doi:10.1093/brain/awac030