Originally found in neuromyelitis optica, this autoantibody has been associated with other conditions. Its current spectrum is as following:

- Seropositive Devic's disease, according to the diagnostic criteria described above

- Limited forms of Devic's disease, such as single or recurrent events of longitudinally extensive myelitis, and bilateral simultaneous or recurrent optic neuritis

- Asian optic-spinal MS - this variant can present brain lesions like MS.

- Longitudinally extensive myelitis or optic neuritis associated with systemic autoimmune disease

- Optic neuritis or myelitis associated with lesions in specific brain areas such as the hypothalamus, periventricular nucleus, and brainstem

- Some cases of tumefactive multiple sclerosis

Though for the most of the cases these diseases are still idiopathic, recent researchs have found the causes for some of them, making them not idiopathic anymore. There are currently two identified auto-antibodies and a genetic variant. The autoantibodies are anti-AQP4 and anti-MOG so far and the genetic variant is a mutation in the gene NR1H3.

Approximately 2 million people in the world suffer from multiple sclerosis Tumefactive multiple sclerosis cases make up 1 to 2 of every 1000 multiple sclerosis cases. This means that only around 2000 people in the world suffer of tumefactive MS. Of those cases, there is a higher percentage of females affected than males. The median age of onset is 37 years.

As in general MS, there are differences for gender, ethnicity and geographic location. Based on epidemiological studies, there are about 3 times more female MS patients than male patients, indicating a possibility of an increased risk due to hormones. Among different ethnic groups, MS is the most common among Caucasians and seems to have a greater incidence at latitudes above 40° as compared to at the equator. While these associations have been made, it is still unclear how they result in an increased risk of MS onset.

Incidence of demyelinating diseases vary from disorder to disorder. Some conditions, such as Tabes dorsalis appear predominantly in males and begins in mid-life. Optic neuritis on the other hand, occurs preferentially in females typically between the ages of 30 and 35. Other conditions such as multiple sclerosis vary in prevalence depending on the country and population. This condition can appear in children as well as adults.

Socioeconomic correlates of health have been well established in the study of heart disease, lung cancer, and diabetes. Many of the explanations for the increased incidence of these conditions in people with lower socioeconomic status (SES) suggest they are the result of poor diet, low levels of exercise, dangerous jobs (exposure to toxins etc.) and increased levels of smoking and alcohol intake in socially deprived populations. Hesdorffer et al. found that low SES, indexed by poor education and lack of home ownership, was a risk factor for epilepsy in adults, but not in children in a population study. Low socioeconomic status may have a cumulative effect for the risk of developing epilepsy over a lifetime.

Prognosis depends on the condition itself. Some conditions such as multiple sclerosis depend on the subtype of the disease and various attributes of the patient such as age, sex, initial symptoms and the degree of disability the patient experiences. Life expectancy in Multiple sclerosis patients is 5 to 10 years lower than unaffected people. MS is an inflammatory demyelinating disease of the

central nervous system (CNS) that develops in genetically susceptible individuals after exposure to unknown environmental trigger(s). The bases for MS are unknown but are strongly suspected to involve immune reactions against autoantigens, particularly myelin proteins. The most accepted hypothesis is that dialogue between T-cell receptors and myelin antigens leads to an immune attack on the myelin-oligodendrocyte complex. These interactions between active T cells and myelin antigens provoke a massive destructive inflammatory response and promotes continuing proliferation of T and B cells and macrophage activation, which sustains secretion of inflammatory mediators. Other conditions such as central pontine myelinolysis have about a third of patients recover and the other two thirds experience varying degrees of disability. There are cases, such as transverse myelitis where the patient can begin recovery as early as 2 to 12 weeks after the onset of the condition.

Balo lesions have been reported alone, but also associated to standard multiple sclerosis, neuromyelitis optica, CADASIL and progressive multifocal leukoencephalopathy

There were also observations that hippocampal sclerosis was associated with vascular risk factors. Hippocampal sclerosis cases were more likely than Alzheimer's disease to have had a history of stroke (56% vs. 25%) or hypertension (56% vs. 40%), evidence of small vessel disease (25% vs. 6%), but less likely to have had diabetes mellitus (0% vs. 22%).

The prognosis of this disease is very variable and can take three different courses: a monophasic, not remitting;

remitting;

and finally, progressive, with increase in deficits.

Balo concentric sclerosis in children has been reported to behave different from adults

Diffuse myelinoclastic sclerosis, sometimes referred to as Schilder's disease, is a very infrequent neurodegenerative disease that presents clinically as pseudotumoural demyelinating lesions, that make its diagnosis difficult. It usually begins in childhood, affecting children between 5 and 14 years old, but cases in adults are possible.

This disease is considered one of the borderline forms of multiple sclerosis because some authors consider them different diseases and others MS variants. Other diseases in this group are neuromyelitis optica (NMO), Balo concentric sclerosis and Marburg multiple sclerosis.

Marburg acute multiple sclerosis, also known as Marburg multiple sclerosis or acute fulminant multiple sclerosis, is considered one of the multiple sclerosis borderline diseases, which is a collection of diseases classified by some as MS variants and by others as different diseases. Other diseases in this group are neuromyelitis optica (NMO), Balo concentric sclerosis, and Schilder's disease. The graver course is one form of malignant multiple sclerosis, with patients reaching a significant level of disability in less than five years from their first symptoms, often in a matter of months.

Sometimes Marburg MS is considered a synonym for tumefactive MS, but not for all authors.

Normally, some measure of improvement appears in a few weeks, but residual signs and disability may persist, sometimes severely.

The disease can be monophasic, i.e. a single episode with permanent remission. However, at least 85% of patients have a relapsing form of the disease with repeated attacks of transverse myelitis and/or optic neuritis. In patients with the monophasic form, the transverse myelitis and optic neuritis occur simultaneously or within days of each other. On the other hand, patients with the relapsing form are more likely to have weeks or months between the initial attacks, and to have better motor recovery after the initial transverse myelitis event. Relapses usually occur early, with about 55% of patients having a relapse in the first year and 90% in the first five years.

It is possible that the relapsing form is related to the antiAQP4+ seropositive status and the monophasic form related to its absence Unlike multiple sclerosis, Devic's disease rarely has a secondary progressive phase in which patients have increasing neurologic decline between attacks without remission. Instead, disabilities arise from the acute attacks.

Approximately 20% of patients with monophasic Devic's disease have permanent visual loss, and 30% have permanent paralysis in one or both legs. Among patients with relapsing Devic's disease, 50% have paralysis or blindness within five years. In some patients (33% in one study), transverse myelitis in the cervical spinal cord resulted in respiratory failure and subsequent death. However, the spectrum of Devic's disease has widened due to improved diagnostic criteria, and the options for treatment have improved; as a result, researchers believe these estimates will be lowered.

The prevalence and incidence of Devic's disease has not been established, partly because the disease is underrecognized and often confused with MS. Devic's disease is more common in women than men, with women comprising over two-thirds of patients and more than 80% of those with the relapsing form of the disease.

A retrospective study found that prevalence of NMOsd was 1.5% inside a random sample of neurological patients, with a MS:NMOsd ratio of 42.7. Among 13 NMOsd patients, 77% had long spinal cord lesions, 38% had severe optic neuritis and 23% had brain or brainstem lesions. Only 56% had clinically definite NMO at follow-up.

According to the Walton Centre in England, "NMO seems to be present across the world unlike MS, which has a higher incidence in temperate climates and white races. Africans and Asians especially in Far East may have a higher risk of NMO, although the exact incidence of this disease is unknown, making specific conclusions difficult". Although many people who have Devic's disease were initially misdiagnosed with MS, 35% of African Americans are often misdiagnosed with MS when they really have NMO.

Devic's disease is more common in Asians than Caucasians. In fact, Asian optic-spinal MS (which constitutes 30% of the cases of MS in Japan) has been suggested to be identical to Devic's disease (differences between optic-spinal and classic MS in Japanese patients). In the indigenous populations of tropical and subtropical regions, MS is rare, but when it appears, it often takes the form of optic-spinal MS.

The majority of Devic's disease patients have no affected relatives, and it is generally regarded as a nonfamilial condition.

A clinically isolated syndrome (CIS) is a clinical situation of an individual's first neurological episode, caused by inflammation or demyelination of nerve tissue. An episode may be monofocal, in which symptoms present at a single site in the central nervous system, or multifocal, in which multiple sites exhibit symptoms. CIS with enough paraclinical evidence can be considered as a clinical stage of Multiple Sclerosis (MS). It can also be retrospectively diagnosed as a kind of MS when more evidence is available.

Brain lesions associated with a clinically isolated syndrome may be indicative of several neurological diseases, like multiple sclerosis (MS) or Neuromyelitis optica. In order for such a diagnosis, multiple sites in the central nervous system must present lesions, typically over multiple episodes, and for which no other diagnosis is likely. A clinically definitive diagnosis of MS is made once an MRI detects lesions in the brain, consistent with those typical of MS. Other diagnostics include cerebrospinal fluid analysis and evoked response testing.

Currently it is considered that the best predictor of future development of clinical multiple sclerosis is the number of T2 lesions visualized by magnetic resonance imaging during the CIS. It is normal to evaluate diagnostic criteria against the "time to conversion to definite".

In 2001, the International Panel on the Diagnosis of Multiple Sclerosis issued the McDonald criteria, a revision of the previous diagnostic procedures to detect MS, known as the Poser criteria. "While maintaining the basic requirements of dissemination in time and space, the McDonald criteria provided specific guidelines for using findings on MRI and cerebrospinal fluid analysis to provide evidence of the second attack in those individuals who have had a single demyelinating episode and thereby confirm the diagnosis more quickly." Further revisions were issued in 2005.

The pathology of the tumefactive demyelinating lesion (TDL) is heterogeneous. In acute phase, the plaques of lesions were characterized by massive demyelination with relatively axonal preservation associated with reactive astrocytosis and infiltration of macrophages. In plaques of chronic lesions, demyelinated lesions with relative axonal preservation and sharply defined margins were major findings. And myelin-laden macrophages accumulate at the edges of plaques and stay inactive

There are several conditions can produce tumefactive lesions. This is known because in some special cases the etiology can be identified. For example, there are some cases of NMO, misidentified as MS and treated with interferon-beta by mistake. Some of these patients developed tumefactive lesions. Anyway, it is important to have into account that NMO itself can also produce them

Some other cases have been found related to viral infection, some others related to NMOSD, others could be paraneoplastic. Also some cases could be related to hormonal treatments

Other possible cause are immunomodulatory combinations. In particular, it has been found that switching from standard MS therapies to fingolimod can trigger tumefactive lesions in some MS patients

While standard multiple sclerosis process has an autoimmune response after the breach of the blood-brain barrier, in tumefactive MS things do not process in the same way, and demyelinating lesions do not always show antibody damage. Subjects with tumefactive multiple sclerosis display elevated levels of choline (Cho)/creatine ratio and increased lactate which is associated with demylinating diseases. Cases also display oligoclonal bands in the cerebrospinal fluid.

The disease is heterogeneous and the lesions do not always comply with the requirements for multiple sclerosis diagnosis (dissemination in time and space). In these cases it is only possible to speak about tumefactive demyelination (TD).

In general, it is accepted that the two main causes of pseudo-tumoral lesions are Marburg multiple sclerosis and acute disseminated encephalomyelitis (ADEM). Tumefactive demyelination of the spinal cord is rare but it has been reported

Damage is not confined to the demyelinating area. Wallerian degeneration outside the lesions has been reported.

Marburg variant of MS is an acute fulminant demyelinating process which in most cases progresses inexorably to death within 1–2 years. However, there are some reports of Marburg MS reaching stability by three years.

Of the phenomena occurring in neurosarcoid, only facial nerve involvement is known to have a good prognosis and good response to treatment. Long-term treatment is usually necessary for all other phenomena. The mortality rate is estimated at 10%

Sarcoidosis has a prevalence of 40 per 100,000 in the general population. However, though those with the GG genotype at rs1049550 in the ANXA11 gene were found to have 1.5-2.5 times higher odds of sarcoidosis compared to those with the AG genotype, while those with the AA genotype had about 1.6 times lower odds. Furthermore, those with Common Variable Immunodeficiency (CVID) may be at even higher risk. One study of 80 CVID patients found 8 of these had sarcoidosis, suggesting as high a prevalence in CVID populations as 1 in 10. Given that less than 10% of those with sarcoidosis will have neurological involvement, and possibly later on in their disease course, neurosarcoidosis has a prevalence of less than 4 per 100,000.

Sarcoidosis most commonly affects young adults of both sexes, although studies have reported more cases in females. Incidence is highest for individuals younger than 40 and peaks in the age-group from 20 to 29 years; a second peak is observed for women over 50.

Sarcoidosis occurs throughout the world in all races with an average incidence of 16.5/100,000 in men and 19/100,000 in women. The disease is most prevalent in Northern European countries and the highest annual incidence of 60/100,000 is found in Sweden and Iceland. In the United States sarcoidosis is more common in people of African descent than Caucasians, with annual incidence reported as 35.5 and 10.9/100,000, respectively. Sarcoidosis is less commonly reported in South America, Spain, India, Canada, and the Philippines. There may be a higher susceptibility to sarcoidosis in those with coeliac disease. An association between the two disorders has been suggested.

The differing incidence across the world may be at least partially attributable to the lack of screening programs in certain regions of the world and the overshadowing presence of other granulomatous diseases, such as tuberculosis, that may interfere with the diagnosis of sarcoidosis where they are prevalent.

There may also be differences in the severity of the disease between people of different ethnicities. Several studies suggest that the presentation in people of African origin may be more severe and disseminated than for Caucasians, who are more likely to have asymptomatic disease.

Manifestation appears to be slightly different according to race and sex. Erythema nodosum is far more common in men than in women and in Caucasians than in other races. In Japanese patients, ophthalmologic and cardiac involvement are more common than in other races.

Sarcoidosis is one of the few pulmonary diseases with a higher prevalence in non-smokers.

Given that some conditions as MS show cortical damage together with the WM damage, there has been interest if this can appear as a secondary damage of the WM. It seems that some researchers claim so.

CNS demyelinating autoimmune diseases are autoimmune diseases which primarily affect the central nervous system.

Examples include:

- Diffuse cerebral sclerosis of Schilder

- Acute disseminated encephalomyelitis

- Acute hemorrhagic leukoencephalitis

- Multiple sclerosis (though the cause is unknown, it is sure that immune system is involved)

- Transverse myelitis

- Neuromyelitis optica

A number of diseases can produce symptoms similar to those of Lyme neuroborreliosis. They include:

- Alzheimer's disease

- Acute disseminated encephalomyelitis

- Viral meningitis

- Multiple sclerosis

- Bell's palsy

Neuroborreliosis presenting with symptoms consistent with amyotrophic lateral sclerosis has been described.

Diagnosis is determined by clinical examination of visible symptoms. Neuroborreliosis can also be diagnosed serologically to confirm clinical examination via western blot, ELISA, and PCR.

The 1996 definition of the clinical courses of MS (phenotypes) was updated on 2013 by an international panel (International Advisory Committee on Clinical Trials).

While the main classification in 1996 was the recovery from the attacks (this clinical feature separates RR from progressive), in the updated revision the main classification is the activity.

MS courses in the new revision are divided into active and non-active, and CIS, when is active on MRI, becomes a kind of RRMS (this, of course, must be retrospectively diagnosed after the CDMS conversion)

Some reviews describe CIS as "the prodromal stage of MS".

Conditions associated with myelitis include:

- Acute disseminated encephalomyelitis: autoimmune demyelination of the brain causing severe neurological signs and symptoms

- Multiple sclerosis: demyelination of the brain and spinal cord

- Neuromyelitis optica or Devic's disease: immune attack on optic nerve and spinal cord

- Sjögren's syndrome: destruction of the exocrine system of the body

- Systemic lupus erythematosus: a systemic autoimmune disease featuring a wide variety of neurological signs and symptoms

- Sarcoidosis: chronic inflammatory cells form as nodules in multiple organs

- Atopy: an immune disorder of children manifesting as eczema or other allergic conditions. It can include atopic myelitis, which causes weakness.

Myelitis occurs due to various reasons such as infections. Direct infection by viruses, bacteria, mold, or parasites such as human immunodeficiency virus (HIV), human T-lymphotropic virus types I and II (HTLV-I/II), syphilis, lyme disease, and tuberculosis can cause myelitis but it can also be caused due to non-infectious or inflammatory pathway. Myelitis often follows after the infections or after vaccination. These phenomena can be explained by a theory of autoimmune attack which states that the autoimmune bodies attack its spinal cord in response to immune reaction.