Seronegative Neuromyelitis Optica (NMO) is a rare and challenging neurological autoimmune disorder. It affects the central nervous system, specifically impacting the optic nerves and spinal cord. The term “seronegative” indicates the absence of certain antibodies typically found in related conditions.
Understanding Seronegative NMO
Neuromyelitis Optica (NMO), also known as Devic’s disease, is a chronic autoimmune disorder. It arises when the body’s immune system mistakenly attacks its own healthy cells within the central nervous system, particularly the myelin sheath and the aquaporin-4 (AQP4) protein on astrocytes. This immune attack leads to inflammation and damage primarily in the optic nerves and spinal cord, and sometimes other areas of the brainstem and brain.
The “seronegative” aspect of NMO refers to the absence of detectable antibodies commonly associated with NMO spectrum disorder (NMOSD). These include Aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies, found in up to 80% of NMOSD cases, and Myelin Oligodendrocyte Glycoprotein (MOG-IgG) antibodies. The lack of these specific antibody markers presents a unique diagnostic challenge, as the underlying cause might be different, potentially involving as-yet-undiscovered antibodies or other non-antibody-mediated mechanisms.
Signs and Manifestations
Seronegative NMO can cause a range of symptoms. These often involve the optic nerves and spinal cord. Symptoms vary in severity and frequency, sometimes occurring as isolated events or in combination.
Optic neuritis, an inflammation of the optic nerve, presents as vision loss, blurred vision, or eye pain, often affecting one eye, sometimes both. Myelitis, or inflammation of the spinal cord, leads to weakness, numbness, or paralysis in the limbs, along with bladder or bowel dysfunction, and severe muscle spasms. Some individuals also experience area postrema syndrome, characterized by intractable nausea, vomiting, or hiccups, which stems from brainstem involvement. Less commonly, brainstem symptoms such as double vision, facial weakness, or swallowing difficulties occur. Rarely, brain lesions manifest as headaches, seizures, or cognitive changes.
Navigating Diagnosis
Diagnosing seronegative NMO presents challenges due to the lack of specific antibody markers. The diagnostic process relies on a combination of clinical presentation, characteristic imaging findings, and careful exclusion of other neurological conditions.
The diagnosis of NMOSD, including seronegative cases, adheres to criteria such as the 2015 International Consensus Diagnostic Criteria. For seronegative individuals, these criteria require more stringent clinical and neuroimaging evidence compared to seropositive cases. Magnetic Resonance Imaging (MRI) of the brain, spinal cord, and optic nerves identifies characteristic lesions and inflammation. Spinal cord lesions in NMO often extend over three or more vertebral segments, and optic nerve lesions may be longitudinally extensive.
A lumbar puncture may be performed to analyze cerebrospinal fluid (CSF). While CSF findings are not always specific for seronegative NMO, they can show elevated white blood cell counts, sometimes with neutrophils, and protein levels. In contrast to multiple sclerosis, oligoclonal IgG bands in CSF are often absent or present in a smaller proportion of NMO patients (10-30%). Ruling out other conditions with similar symptoms, such as multiple sclerosis (MS), is important, as NMO requires different treatments than MS.
Current Management Approaches
Managing seronegative NMO involves two primary goals: treating acute attacks and preventing future relapses. The aim is to reduce inflammation during attacks and minimize the accumulation of neurological disability over time.
For acute attacks, high-dose corticosteroids, such as intravenous methylprednisolone, are the first-line treatment to reduce inflammation. If attacks are severe or unresponsive to steroids, plasma exchange (PLEX) is considered. PLEX involves removing blood, separating blood cells from plasma, and returning the cells with a replacement solution, which helps eliminate harmful antibodies and inflammatory factors.
Long-term management focuses on preventing new attacks through ongoing immunosuppressive therapy. Non-specific immunosuppressants like azathioprine, mycophenolate mofetil, and rituximab are used. Rituximab, an anti-CD20 monoclonal antibody, has shown efficacy in reducing relapse rates in both seropositive and seronegative patients. While newer targeted therapies like eculizumab, satralizumab, and inebilizumab were approved for AQP4-IgG seropositive NMOSD, their effectiveness in seronegative cases is less clear. Supportive care, including pain management, physical therapy, and occupational therapy, also plays a role in managing symptoms and improving quality of life.