Inflammation Drives Nerve Damage in Early MS, Imaging Study Shows

Inflammation drives the loss of brain volume and thinning of the eye’s retina in the first five years of a multiple sclerosis (MS) diagnosis, an imaging study demonstrates. 

The findings support a therapeutic strategy of halting inflammatory activity during this initial period. 

The study, “Retinal and brain damage during multiple sclerosis course: inflammatory activity is a key factor in the first 5 years,” was published in the journal Nature Scientific Reports. 

MS is caused by the immune system attacking the myelin sheath, the protective coating around nerve fibers called axons. This results in inflammation that further damages axons (axonal loss), leading to neuron degeneration and clinical disability. 

New methods using imaging techniques to measure axon damage have helped in the understanding of MS disease progression, such as MRI to quantify brain volume, or optical coherence tomography (OCT) to determine the thickness of the eye retina. 

In the study, researchers based at the University of Barcelona used MRI and OCT to measure the impact of local (focal) inflammation on axon damage in 161 people with MS who had been followed for at least five years.

“Understanding the drivers of neuro-axonal injury and in particular, the role of focal inflammation, a treatable feature of the disease, is paramount to the design of therapeutic strategies,” the researchers wrote.

Participants were part of the Barcelona MS-Visualpath cohort who underwent annual neurological, ophthalmological (eye), and MRI examinations for up to three years, then bi-annually after.

The median age of the patient group analyzed was 40.47 years, with a median disease duration of 6.99 years. About 70.2% of the group was female. 

A total of 139 patients had relapsing-remitting MS (RRMS), 10 were diagnosed with primary progressive MS (PPMS), five with secondary progressive MS (SPMS), and seven had clinically isolated syndrome (CIS).

Focal inflammatory activity (active MS) was defined as the presence of one or more relapses or new/enlarging lesions identified during the evaluation period. Inflammatory activity was found in 107 patients (66.46%).

Results showed that MS patients had a higher rate of brain volume loss and retinal thinning in the first five years of the disease. This was particularly pronounced in patients with active disease in terms of whole brain volumes, and also in the area of the brain that relays signals (the thalamus), and the ganglion cell plus inner plexiform layer (GCIPL) — two retina layers that contain the cell bodies of nerve cells.

After five years, rates of brain volume loss and retinal thinning stabilized, and were similar in patients with active disease and in those with stable disease. 

According to statistical analysis, the speed of retinal thinning and whole-brain volume loss was nearly two times faster in patients with active disease than in those with stable disease during the first two years of MS onset, with thalamic volume loss occurring approximately five times faster. These differences disappeared five years after MS onset. 

No significant associations were found between changes in retinal layer thickness and sex, age at onset, or disease-modifying medications. In contrast, there was a significant association between age at MS onset and the change in grey matter volume with similar trends for whole brain and thalamus. 

“Nevertheless, the magnitude of the effect was relatively weak compared to that of inflammation,” the researchers wrote. 

“In conclusion, there is an accelerated rate of brain and retinal neuro-axonal damage in the early stages of the MS disease course driven by focal inflammatory activity,” the team concluded. “Consequently, a beneficial neuroprotective strategy should focus on halting inflammatory activity during this optimal treatment window.”