NMOSD Diagnosis Without AQP4 Antibodies Requires More Scrutiny

Report describes the case of 35-year-old man in Nepal

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Reaching a neuromyelitis optica spectrum disorder (NMOSD) diagnosis in the absence of disease-causing antibodies requires careful attention from physicians in order to ensure timely treatment.

That suggestion comes from a case report of a man in Nepal who had symptoms of the autoimmune disease but lacked the antibodies against the aquaporin 4 (AQP4) protein that often are used as diagnostic criteria.

According to the researchers, the findings demonstrate that “increased scrutiny is the key in the detection of NMOSD with seronegative status,” or lacking disease-associated antibodies.

“Further development of diagnostic modalities in seronegative neuromyelitis optica spectrum disorder is required,” they added.

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The case report, “Seronegative neuromyelitis optica spectrum disorder with longitudinally extending transverse myelitis and optic neuritis: A case report,” was published in the journal Annals of Medicine and Surgery.

NMOSD can present with similar clinical signs to other autoimmune conditions, like multiple sclerosis (MS), which can delay an accurate diagnosis. But lab tests can help to distinguish NMOSD because patients have antibodies specific to the disease that aren’t seen in MS. In particular, most patients are positive for antibodies that target AQP4, a finding highly specific for NMOSD.

Current diagnostic criteria, updated in 2015, stipulate that patients must have anti-AQP4 antibodies in addition to one of six core clinical characteristics. These characteristics include: myelitis (inflammation of the spinal cord), optic neuritis (inflammation of the optic nerve), or involvement in any of four particular brain regions — the diencephalon, cerebrum, brainstem, or area postrema of the dorsal medulla.

For patients who don’t have those antibodies, the criteria are more stringent. These patients must have at least two of the six core characteristics, in addition to other specific features seen on MRI.

A research team in Nepal now reported the case of a 35-year-old man eventually diagnosed with NMOSD who did not have AQP4 antibodies.

He had reported to the emergency room with complaints of lower limb weakness on both sides and a loss of bowel and bladder control for two days. He said the weakness was present below both knee joints, causing difficulty walking that later progressed to an inability to walk. The man also reported a history of tuberculosis.

No significant findings were observed on a general exam, but the man had exaggerated reflexes, and low muscle tone. He also had reduced sensations below the knee.

A test of the fluid surrounding the spinal cord revealed high levels of protein and immune cells. MRI scans showed signs of myelitis, a core NMOSD characteristic, which was treated with the immunosupressant azathioprine and steroids.

At the hospital, the man began to experience blurred vision in his left eye, and another MRI suggested he also had optic neuritis, another core characteristic. He was given an additional course of steroids.

New tests of the spinal fluid were run to look for antibodies linked to NMOSD and MS. He tested negative for AQP4 antibodies, but also for markers of MS.

Seronegative NMOSD

Ultimately, the man met the criteria for seronegative NMOSD, with two core characteristics (myelitis and optic neuritis) and characteristic MRI findings. Additional tests were done to rule out the presence of latent tuberculosis.

He was maintained on a treatment course of azathioprine and tapering oral steroids, with a plan to begin rituximab. He was discharged from the hospital and physiotherapy was recommended.

The man was re-admitted to the hospital two weeks later due to a relapse, at which time the immunosupressant rituximab was begun. At the hospital, his condition did not improve.

He was discharged with continuous physiotherapy and recommendations for palliative care. “We could not do adequate follow up with the patient after he was discharged for the second time,” the researchers wrote.

They emphasized the importance of a timely diagnosis for NMOSD patients. “It becomes increasingly crucial as NMOSD is associated with poor prognosis,” the scientists wrote, noting that the prognosis is especially poor for patients with a relapsing disease course.

“Prompt diagnosis and management to reduce relapse is necessary. Thus, further understanding of seronegative NMOSD is required,” the team concluded.