Age at Onset of NMOSD Influences Disease Presentation, Prognosis

Older age linked with greater chance of spinal cord involvement, greater disability

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The onset of neuromyelitis optica spectrum disorder (NMOSD) at an older age is linked with a greater likelihood of spinal cord involvement at the first disease attack, fewer relapses, and greater disability, according to a study in China.

“Age of disease onset correlates with clinical characteristics and prognostic outcomes in patients with NMOSD,” the researchers wrote, noting that the findings warrant larger studies in the future.

The study, “Age of onset correlate with clinical characteristic and prognostic outcomes in neuromyelitis optica spectrum disorder,” was published in Frontiers in Immunology. 

A feature of NMOSD is inflammation that affects the optic nerve (optic neuritis) and the spinal cord (transverse myelitis). The optic nerve sends and receives signals between the eye and the brain.

By conventional classifications, NMOSD can be considered early-onset (EO-NMOSD) or late-onset (LO-NMOSD) based on the age when symptoms emerge, with the former starting before age 50 and the latter at 50 or older.

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Association of age of onset with NMOSD characteristics

A number of studies have shown that NMOSD attack type, relapse rates, permanent disability, and pain related to nerve damage might be influenced by the age at onset.

“However, some of these results were inconsistent due to limited sample size, mixed ethnicity, and incomplete clinical information,” the researchers wrote, leading them to review the medical records of 298 NMOSD patients (248 women) at Xiangya Hospital, Changsha, China, between January 2016 and December 2021. They specifically examined their’ clinical characteristics when stratified by age of disease onset.

All had been followed for at least six months and tested for antibodies against aquaporin-4 (AQP4), the most common target of NMOSD-causing antibodies. As expected, most (82.9%) were positive for these antibodies.

Their mean age at disease onset was about 46 and they had NMOSD for a mean of 41.4 months, or nearly 3.5 years. A total of 164 patients (55%) were considered to have EO-NMOSD, with a mean onset age of 35.4, while 134 (45%) had LO-NMOSD, with a mean age at onset of 59.5.

Results showed a significantly greater proportion of LO-NMOSD patients had transverse myelitis in their first attack relative to EO-NMOSD patients (58.2% vs. 36%).

Patients with a later disease onset were less likely to have optic neuritis (23.1% vs. 34.8%) and brain involvement (7.5% vs. 18.3%) in their first attack than those with EO-NMOSD.

Late-onset patients showed longer segments of lesioned spinal cord at the time of their first attack as well as at their last follow-up compared with EO-NMOSD patients, but showed fewer NMOSD-typical brain lesions on MRI scans.

The findings indicate “differences in anatomical susceptibility in patients with different onset age, that the optic nerve and brain were more susceptible in young patients, while the spinal cord was more vulnerable in aged patients,” the researchers wrote.

Recurrent NMOSD attacks (relapses) were significantly less common in patients with late-onset disease than in early-onset disease (74.6% vs. 84.2%).

Still, at last follow-up, late-onset patients had a significantly higher level of disability, as well as significantly greater rates of motor dysfunction (29.9% vs. 15.9%) and severe motor dysfunction (12.7% vs 5.5%).

“The proportion of visual disability and death rate was similar between the two groups,” the researchers wrote.

Comparing very late-onset, relative late-onset

Comparable findings were observed among patients with very-late disease onset, age 70 or older, with those with relative-late-onset (between 50–69).

Patients with very-late disease onset were significantly more likely to have transverse myelitis during their first attack, have longer segments of lesioned spinal cord, and exhibit greater disability at their last follow-up compared with those with relative-late onset.

Group differences held when the researchers looked only at patients positive for anti-AQP4 antibodies.

The team found that the proportion of patients with transverse myelitis during their first attack and over the entire disease course increased with advancing age at disease onset.

A similar trend was found for the length of spinal cord lesions at first attack and at last follow-up, and for disability at last follow-up.

In contrast, increasing age at onset was associated with a lower annualized relapse rate excluding the first attack. No significant link was found between age of onset and annualized relapse rates including the first attack.

These findings suggest the relatively more severe disability accumulation in late-onset NMOSD “was less likely accumulated through frequent relapses,” and may be due to a higher proportion of transverse myelitis at disease onset and deficient reparation mechanisms at first attack in aged patients, the researchers said.

While the reasons why these older patients demonstrate larger spinal lesions are unknown, it could be due to more extensive inflammation during their fewer relapses, they suggested.

The results underscore the differences in clinical features and prognostic outcomes between early- and late-onset NMOSD.

“These findings need to be further confirmed in prospective studies with larger sample size and strictly controlled multiple variables,” the researchers said.