Devic's Syndrome (Neuromyelitis Optica)

An autoimmune condition, Devic’s Disease is known by a number of different names including:

1. Neuromyelitis Optica
2. Devic Syndrome
3. Optic Neuromyelitis
4. Opticomyelitis

Summary

Devic’s Disease (DD), to use one of the names it is known by, is a disease of the autoimmune system that presents in a very similar way to multiple sclerosis.

A chronic condition which directly affects nerve tissue, DD specifically involves the optic nerves and the spinal cord, causing inflammation of both. The former is known as optic neuritis and the latter as myelitis.

DD can typically by split into two different classifications, one where individuals suffer a number of recurrent attacks, but once this phase passes, no further episodes occur. This is often described as monophasic DD and is far rarer. The other form which is far more common is distinguished by a number of attacks alternating with periods of remission. The attacks may be relatively close together, separated by just days or at the opposite end of the spectrum, may be years apart.

It is the latter remitting relapsing form which can often appear to be very similar to multiple sclerosis.

Presenting features

DD presents with either myelitis or optic neuritis as the initial symptom, features which can be present in a number of other conditions. At the earlier stages this can make the diagnosis of DD much more difficult to reach, with the need to exclude other conditions.

When the optic nerve becomes inflamed, the individual suffers pain within the affected eye following by a loss of visual acuity. The presentation is typically unilateral but occasionally, the optic neuritis may be bilateral. In some cases an upper respiratory tract infection may precede the presentation of optic neuritis in DD but this may not always be the case.

Myelitis is the other primary symptom which is often seen, more specifically transverse myelitis, where there is a total involvement of autonomic, sensory and motor functions which are below the given point. Individuals may suffer pain in both the limbs and the spine along with varying degrees of paralysis, ranging from paraparesis to paraplegia, in the legs. There may also be associated loss of control of the bladder and bowel.

Accompanying these symptoms, upon observation the deep tendon reflexes may be reduced or even completely absent at first, but later may become amplified. Sensory loss may also be present.

When transverse myelitis is the presenting symptoms, there may be headaches, neck pain, a stiff back and limb pain. Because of the diverse nature of transverse myelitis, it can be extremely challenging to identify the cases which are associated with DD and those which are idiopathic.

Regardless of whether the myelitis or the optic neuritis are the initial presenting features, multiple sclerosis (MS) may be seriously considered as a possible diagnosis for some time. This is because both of these conditions are also present with MS. However, one indicator is the severity of the presentation because with DD, the symptoms tend to be far more severe. In addition, DD does not normally feature oligoclonal bands within the spinal fluid, a typical feature of MS, so carrying out a lumbar puncture can help to clarify the cause.

Although the initial symptoms of DD are extremely serious, with paralysis and loss of vision, high dose corticosteroids can effect a good result, and at the very least a partial recovery of key functions such as bladder and bowel control, motor, vision and sensory can be achieved. However for those individuals who suffer recurrent attacks there is the risk of a permanent visual defect, including blindness, or impaired mobility.

Further symptoms may develop later in the disease progression such as lesions within the brain which can result in persistent hiccups or vomiting. These symptoms are specifically linked to brain stem inflammation and in some cases may be the initial presenting features of DD. Hypothalamic and brainstem syndromes, along with forebrain inflammation are common, and may occur in tandem with oedema.

Aetiology and epidemiology

Not all individuals suffer with both myelitis and optic neuritis, in some the symptoms are restricted to just one type of manifestation. These often result from neuromyelitis and neuromyelitis optica related to testing positive for aquaporin-4 autoantibodies.

Experts believe that individuals who are positive for the aquaporin-4 should be considered as having DD, even with these isolated features.

Aquaporin-4 is a protein which is present within the central nervous system and is one of those most frequently attacked by the autoimmune system, causing the symptoms of DD. Although these attacks are prompted by an autoimmune disease, no-one as yet has been able to identify the trigger.

Researchers have also identified the presence of myelin oligodendrocyte glycoprotein antibodies in some cases, particular those which are non-relapsing. This is believed to play a role.

A family or personal history of autoimmunity appears to play a significant role in the development of DD, being present in roughly half of all cases. However, a specific history of DD is less common with approximately 95% of cases having no documented instances elsewhere within the family.

The incidence of DD is around 1-5 cases per 100,000 births and although there’s no particular indicator for either gender being more at risk, women who have reached middle age appear to be the most likely group to be affected. This is particularly the case with the remitting/relapsing form, where women are 4-5 times more likely than men to be diagnosed. Monophasic DD appears to occur in equal numbers among both genders.

DD is not confined to adults, children can also be diagnosed. When affected, brain symptoms are more frequently evident at the onset rather than developed later and in the majority of cases the presentation is monophasic.

There are no risks of contagion associated with DD.

Diagnosis

A diagnosis of DD can be established by a combination of clinical assessment, an in-depth patient history, the presence of characteristic features and the results of a number of different investigations.

Some of the tests you can expect to see carried out include:

1. Lumbar puncture
2. CT scan
3. Blood tests
4. X-rays
5. MRI scan

The NMO-IgG blood test is particularly useful for DD, being very specific and reasonably sensitive. This test is able to detect the specific antibodies for aquaporin-4. Therefore, this may be one of the very first tests carried out because a positive result may be returned even before the full clinical picture is evident.

The lumbar puncture allows the cerebrospinal fluid to be examined. The presence of oligoclonal bands points towards a diagnosis of MS, while a higher rise in white blood cells accompanied by the presence of a certain type of neutrophil would indicate DD.

Differential diagnosis

Like many neurological disorders, the initial presentation can be similar to other conditions and it’s necessary to undergo thorough investigations to be able to distinguish one from another.

The differential diagnosis which might be under consideration includes the following conditions:

Multiple Sclerosis

Optic neuritis can be one of the initial presenting features of MS, so it’s perhaps understandable that it can be difficult initially to differentiate it from DD. In MS multiple plaques form throughout the spinal cord and the brain, eroding the myelin sheath surrounding the nerves. This prevents the efficient transmission of signals throughout the nervous system.

Although life expectancy for individuals with MS is not greatly altered, the condition can be progressive, as well as remitting.relapsing and stable. Some of the symptoms individuals suffer include abnormal sensory perceptions, visual disorders, difficulties with gait and mobility, impairment of speech and disruption to bladder and bowel function.

Acute disseminated encephalomyelitis (post-infectious encephalitis)

A condition affecting the central nervous system, acute disseminated encephalomyelitis presents with inflammation to both the spinal cord and the brain caused by damage to the fatty nerve sheath tissue. This may occur as a result of either a vaccination or a viral infection but in some cases can manifest spontaneously.

Lupus (systemic lupus erythematosus)

An inflammatory condition arising within the connective tissue throughout the whole body, lupus can affect not just the joints and skin but the internal organs too. An immunological condition, young women aged between 15-35 are most commonly diagnosed.

Both optic neuritis and transverse myelitis have on occasions been diagnosed in individuals with lupus but research suggests that in a large number of these cases, NMO-IgG antibodies are present. This suggests that in fact, DD is present in addition to the lupus.

Sarcoidosis

Affecting both the spinal corn and the optic nerves when it manifests within the central nervous system, sarcoidosis is a granulomatous condition. Often affecting the respiratory system, it can be both asymptomatic or symptomatic, and enlarged lymph glands may be visible on an Xray.

When the sarcoid is present within the central nervous system, it rarely affects other parts of the body. The long extension of lesions within the spinal cord which are characteristic of DD may be also seen in sarcoidosis but the symptoms present far more slowly, and are often slower to respond when treated with corticosteroids.

Paraneoplastic disorders

When cell damage or inflammation is caused by an autoimmune reaction to cancer, it is referred to as a type of paraneoplastic disorder. Some of these types of syndrome result in either optic neuritis or a widespread myelitis which may be difficult to distinguish from DD. This may particularly be the case for those instances where there is a collapsing response mediated protein 5.

Treatment

A high dose of corticosteroids, usually methylprednisolone is the standard treatment for acute episodes.

When IV corticosteroids aren’t effective, plasma exchange can be offered for attacks which are severe. To do this, some of the blood needs to be removed and the plasma separated. The remaining blood cells are then combined with a replacement plasma solution and then reintroduced. This is a very similar process to the way in which dialysis works on the kidneys.

Long term treatment is a very different matter, but to date, there has been no monitored clinical trials. However, most physicians believe that immunosuppressive drugs should be prescribed in the first instance with rituximab, mofetil, mycophenolate, azathioprine and corticosteroids the most frequent choices, typically a combination.

Where first line immunosuppressive treatments have failed, rituximab has been demonstrated as having some success. Although the condition has some similarities with MS, the immunomodulatory treatments used for MS are in effective for DD. Some treatments, such as interferon beta can even be harmful.

Low dose carbamazepine is also used in treatment regimes as a means of reducing paroxysmal tonic spasms which can occur in tandem with episodes of neuromyelitis optica. Those who have irreversible loss of motor function may also develop rigidity which can be treated with additional anti-spasticity agents.

Prognosis

The outcome of DD is very variable depending on the form of the disease suffered and the extent of the symptoms.

In the very worst cases where there is brain stem involvement, artificial respiration may be required or death may even occur.

Some individuals have an almost total recovery with little or no sequelae. Others may have a permanent visual deficit or a weakness which affects mobility, requiring the assistance of aids such as walking sticks or a wheelchair.

In general, it is believed that early intervention can lead to a preferential outcome.