Subset of NMOSD patients may have benign disease course

Some NMOSD patients do not exhibit significant disability for 15 years, study shows

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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A small subset of people with neuromyelitis optica spectrum disorder (NMOSD) do not accumulate significant functional disability in the 15 years following symptom onset, according to a recent study.

Called benign NMOSD, these patients were more likely to be Caucasian, less likely to have spinal cord involvement at disease onset, and had lower relapse rates than their counterparts with higher levels of disability.

Still, future studies should look more closely at quality of life measurements to assess “the real impact of ‘benign’ NMOSD … on patients’ life,” the researchers wrote.

The study, “Neuromyelitis optica spectrum disorders with a benign course.Analysis of 544 patients,” was published in Multiple Sclerosis and Related Disorders.

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Guidelines to aid diagnosis of NMOSD published

NMOSD is a rare autoimmune disease that leads to inflammation of the spinal cord and optic nerve, which relays signals between the eyes and the brain. Most patients experience flare-ups of symptoms, or relapses, associated with visual and spinal cord dysfunction interspersed with periods of recovery.

Since relapses are associated with increasing disability, patients tend to become more functionally impaired over time. For some patients, this can mean a complete loss of vision or becoming entirely wheelchair-bound in the years after diagnosis due to recurring relapses.

However, it is possible for patients to have a milder disease course in which they retain good neurological function and experience only mild-to-moderate disability for at least a decade after disease onset.

This so-called benign disease has been well-described in people with multiple sclerosis (MS), a related autoimmune disease, but there are few reports of this disease course in NMOSD patients.

Research in Brazil

A team of researchers in Brazil now sought to learn more about the clinical factors associated with benign NMOSD by analyzing the medical records from 535 NMOSD patients seen at Brazilian MS centers.

Patients were classified as having benign disease if they had lived with NMOSD for at least 15 years and showed no-to-moderate disability at their last follow-up, as reflected by a score no higher than 3 on the Expanded Disability Status Scale (EDSS). Ranging from 0-10, a higher EDSS score reflects worse disability.

“Patients with sustained EDSS score [above] 3.0 during the disease course were classified as having non-benign NMOSD, whereas those with EDSS [below] 3.0 and disease duration shorter than 15 years were not qualified for classification,” the researchers wrote.

A total of 16 patients met the benign disease criteria — representing 3% of all patients and 4.2% of the 378 patients whose disease could be classified.

The remaining 362 patients (95.8%) had an EDSS score higher than 3 and were classified as having non-benign disease. Of them, 99 people had been living with NMOSD for at least 15 years and 263 had a disease duration of less than 15 years [Fig.1].

All 16 individuals in the benign group were women and 12 (75%) were Caucasian. They first had developed symptoms at a median age of 28, and 75% were positive for antibodies against the aquaporin-4 protein, the most common type of NMOSD-causing antibodies.

Most common NMOSD symptoms

In this group of patients, the most common first NMOSD symptom was optic nerve inflammation — occurring in 62.5% of patients. The second-most common initial symptom was area postrema syndrome (25%), which is characterized by uncontrolled nausea, vomiting, and hiccups.

These symptoms were more common as the initial disease presentation in benign patients versus non-benign patients. For the latter group, patients were significantly more likely to present with spinal cord inflammation (myelitis).

While all patients with benign disease had a relapsing disease course, they tended to experience fewer relapses in the first year and first three years after disease onset relative to those with non-benign disease. Importantly, the benign group had a significantly lower mean annualized relapse rate (ARR) than the non-benign group (0.22 vs. 0.57).

As expected, patients with benign disease had significantly lower EDSS scores at their last follow-up visit, in addition to having significantly better visual function.

Also, “a smaller group of six patients were fully functional in all neurological systems at the last follow-up more than 20 years after disease onset,” the team wrote.

Statistical analyses showed that being non-Caucasian, having myelitis as a first disease presentation, and having a higher ARR were each significantly associated with a higher chance of having non-benign disease, meaning these represented negative risk factors for benign NMOSD.

An ARR higher than 0.4 was found to be the cut-off above which severe disability was more likely to occur, which “confirms previous evidence that the frequency of relapses highly impacts NMOSD outcome,” the researchers wrote.

“Therefore, prompt therapeutic intervention with high-efficacy drugs to prevent relapses may increase the group of benign NMOSD patients,” they added.

Overall, “preservation of full neurological function for [at least] 15 years after disease onset distinguishes a small group of NMOSD from the conventional form of the disease which is characterized by severe disability,” the scientists wrote.

Continuous monitoring needed

However, since “NMOSD patients may develop new disabling relapses after 10 or 15 years of remission,” the team wrote, continuous monitoring is needed for all patients, even those with benign disease.

“Research on genetic factors that impact outcome may also open new windows for future gene therapy providing most NMOSD patients with an extended benign disease course,” the team concluded.