Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD)

Neuromyelitis optica (NMO) or NMO spectrum disorder (NMOSD) is a rare autoimmune disease classified as a central nervous system inflammatory demyelinating disease. It was formerly known as Devic’s disease, having first been described by Eugène Devic, a French neurologist, at the end of the 19th century.

While NMO generally affects the optic nerves and/or spinal cord, which explains its name, other areas of the brain can also be affected, so today we use the term NMO spectrum disorder or NMOSD. This disease was for a long time considered to be a form of multiple sclerosis (MS). However, recent findings indicate that NMOSD and MS are distinct diseases requiring different management strategies (more information here).

Of unknown origin, NMOSD generally manifests around the age of 40, but can also occur in children and elderly adults (over the age of 80). It affects women more than men: 7 to 1 in adults and 3 to 1 in children. In patients with this disease, the immune system is dysregulated and attacks the body’s own cells as if they were foreign, hence its classification as an autoimmune disease.

What are the symptoms of NMOSD?

The symptoms of NMOSD vary from one person to another. They generally appear suddenly and rapidly, in the form of “attacks”.

Optic neuritis (ON) is the most common manifestation of NMOSD before the age of 40 (read more about optic neuritis here). In patients with NMOSD, ON attacks are severe, with a significant decrease in visual acuity and frequent sequelae.

Spinal cord involvement is also common, usually in the form of acute transverse myelitis. This can result in motor, sensory, bowel or bladder impairment (read more about transverse myelitis here).

Area postrema syndrome is the third most common presentation of NMOSD. The area postrema of the brainstem is a structure of the brain that controls vomiting. Area postrema syndrome often leads to a delay in making the diagnosis as it causes symptoms resembling digestive issues such as prolonged nausea, typically lasting several hours (generally more than 6 hours), episodic vomiting over several days with numerous episodes per day, and hiccups lasting over 48 hours.

These symptoms usually disappear, but it is essential to identify this syndrome in order to prevent the risk of a future attack, which could cause other, much more serious symptoms. Patients with NMOSD may also present with double vision, facial paralysis, vertigo, sleep disorders (narcolepsy or hypersomnia), eating disorders (hyperphagia), disturbances in body temperature regulation, or low blood sodium levels linked to the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Other rare manifestations reported in patients with NMOSD include: acute disseminated encephalomyelitis (read more here), isolated hearing loss, opsoclonus-myoclonus syndrome (combination of involuntary, jerky, uncontrolled, multidirectional eye movements and brief involuntary muscle contractions), hydrocephalus (accumulation of cerebrospinal fluid in the brain that can lead to vomiting, lethargy, headaches, and seizures), and elevated creatine phosphokinase (CPK) levels in the blood, which can be asymptomatic, but are most often associated with muscle pain (myalgia) or myositis (muscle weakness).

Some patients may experience cognitive impairments following an attack of NMOSD, such as attention deficits, memory loss and/or impaired speed of information processing, sometimes associated with symptoms characteristic of depression.

NMOSD attacks can be very severe, with a high potential for disability starting from the first episode. They therefore require rapid and appropriate management and treatment to limit their consequences. To achieve this, they must be diagnosed quickly and correctly.

How is NMOSD diagnosed?

Until very recently, the diagnosis of NMOSD was based on clinical symptoms, in particular the combination of visual involvement (optic neuritis) and spinal cord involvement (myelitis). The discovery of antibodies to aquaporin-4 (AQP4), a protein that is vital to the proper functioning of the central nervous system (brain, spinal cord, optic nerve), in the blood of patients with NMOSD has facilitated the process of diagnosis. Around 70% of NMOSD patients have antibodies to this protein (anti-AQP4 antibodies) in their blood. The association of this biomarker with a single attack causing damage to the nervous system is sufficient to make the diagnosis of NMOSD. Among patients who do not have anti-AQP4 antibodies in their blood, the diagnosis is based on the occurrence of at least two attacks associated with specific abnormalities observed on brain and spinal cord magnetic resonance imaging (MRI). The neurologist also considers the results from a lumbar puncture and other tests and examinations in order to rule out other conditions that may be causing similar symptoms (differential diagnosis).

Rapid recognition of an NMOSD attack allows for appropriate management and treatment to be initiated and significantly improves the prognosis. However, the rarity of NMOSD, combined with the lack of awareness about it and the complexity of the diagnostic criteria for patients without anti-AQP4 antibodies in their blood, can result in diagnostic wandering and a risk for severe disability.

Apart from truly exceptional cases, NMOSD does not progress between attacks. Controlling attacks can thus control the disease and prevent severe and permanent disability

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