The theory of autoimmune attack claims that a person with neuroimmunologic disorders have genetic predisposition to auto-immune disorder, and the environmental factors would trigger the disease. The specific genetics in myelitis is not completely understood. It is believed that the immune system response could be to viral, bacterial, fungal, or parasitic infection; however, it is not known why the immune system attacks itself. Especially, for immune system to cause inflammatory response anywhere in the central nervous system, the cells from immune system must pass through the blood brain barrier. In the case of myelitis, not only is the immune system dysfunctional, but the dysfunction also crosses this protective blood brain barrier to affect the spinal cord.

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.

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.

The role of prolonged cortical myelination in human evolution has been implicated as a contributing factor in some cases of demyelinating disease. Unlike other primates, humans exhibit a unique pattern of postpubertal myelination, which may contribute to the development of psychiatric disorders and neurodegenerative diseases that present in early adulthood and beyond. The extended period of cortical myelination in humans may allow greater opportunity for disruption in myelination, resulting in the onset of demyelinating disease. Furthermore, it has been noted that humans have significantly greater prefrontal white matter volume than other primate species, which implies greater myelin density. Increased myelin density in humans as a result of a prolonged myelination may therefore structure risk for myelin degeneration and dysfunction. Evolutionary considerations for the role of prolonged cortical myelination as a risk factor for demyelinating disease are particularly pertinent given that genetics and autoimmune deficiency hypotheses fail to explain many cases of demyelinating disease. As has been argued, diseases such as multiple sclerosis cannot be accounted for by autoimmune deficiency alone, but strongly imply the influence of flawed developmental processes in disease pathogenesis. Therefore, the role of the human-specific prolonged period of cortical myelination is an important evolutionary consideration in the pathogenesis of demyelinating disease.

A demyelinating disease is any disease of the nervous system in which the myelin sheath of neurons is damaged. This damage impairs the conduction of signals in the affected nerves. In turn, the reduction in conduction ability causes deficiency in sensation, movement, cognition, or other functions depending on which nerves are involved.

Some demyelinating diseases are caused by genetics, some by infectious agents, some by autoimmune reactions, and some by unknown factors. Organophosphates, a class of chemicals which are the active ingredients in commercial insecticides such as sheep dip, weed-killers, and flea treatment preparations for pets, etc., will also demyelinate nerves. Neuroleptics can also cause demyelination.

Demyelinating diseases are traditionally classified in two kinds: demyelinating myelinoclastic diseases and demyelinating leukodystrophic diseases. In the first group a normal and healthy myelin is destroyed by a toxic, chemical or autoimmune substance. In the second group, myelin is abnormal and degenerates. The second group was denominated dysmyelinating diseases by Poser

In the most known example, multiple sclerosis, there is good evidence that the body's own immune system is at least partially responsible. Acquired immune system cells called T-cells are known to be present at the site of lesions. Other immune system cells called Macrophages (and possibly Mast cells as well) also contribute to the damage.

Vitamin B12 deficiency can cause demyelination.

Transverse myelitis is a neurological condition in which the spinal cord is inflamed. The inflammation damages nerve fibers, and causes them to lose their myelin coating leading to decreased electrical conductivity in the central nervous system. "Transverse" implies that the inflammation extends across the entire width of the spinal cord. Partial transverse myelitis and partial myelitis are terms used to define inflammation of the spinal cord that affects part of the width of the spinal cord.

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

Myelopathy describes any neurologic deficit related to the spinal cord. When due to trauma, it is known as (acute) spinal cord injury. When inflammatory, it is known as myelitis. Disease that is vascular in nature is known as vascular myelopathy. The most common form of myelopathy in human, "cervical spondylotic myelopathy (CSM)", is caused by arthritic changes (spondylosis) of the cervical spine, which result in narrowing of the spinal canal (spinal stenosis) ultimately causing compression of the spinal cord. In Asian populations, spinal cord compression often occurs due to a different, inflammatory process affecting the posterior longitudinal ligament.

The treatment and prognosis of myelopathy depends on the underlying cause: myelopathy caused by infection requires medical treatment with pathogen specific antibiotics. Similarly, specific treatments exist for multiple sclerosis, which may also present with myelopathy. As outlined above, the most common form of myelopathy is secondary to degeneration of the cervical spine. Newer findings have challenged the existing controversy with respect to surgery for cervical spondylotic myelopathy by demonstrating that patients benefit from surgery.

There are disturbances in sensory nerves and motor nerves and dysfunction of the autonomic nervous system at the level of the lesion or below. Therefore, the signs and symptoms depend on the area of spine involved:

- Cervical: If the upper cervical cord is involved, all four limbs may be involved and there is risk of respiratory paralysis (cervical nerve segments C3, 4, 5 innervate the abdominal diaphragm). Lesions of the lower cervical (C5–T1) region will cause a combination of upper and lower motor neuron signs in the upper limbs, and exclusively upper motor neuron signs in the lower limbs. Cervical lesions account for about 20% of cases.

- Thoracic: A lesion of the thoracic spinal cord (T1–12) will produce upper motor neuron signs in the lower limbs, presenting as a spastic diplegia. This is the most common location of the lesion,

Acute flaccid myelitis (AFM) is a neurologic illness of sudden onset in children. It presents with localised limb weakness of unknown cause. Enterovirus 68, which as a member of the enterovirus family, is related to polio, is a leading candidate for the cause of the condition. Due to the recent emergence of the condition, the existing literature about it is tentative and should not be taken as established medical opinion. There is no established treatment for the condition or the virus that may cause it.

At the October 23 meeting of the Child Neurology Society, it was a matter of debate whether acute flaccid myelitis would be likely to return the next year. Enteroviruses D68 and A71 tend to cause neurological symptoms more often than other enteroviruses, but have been infrequent causes of colds. It is possible that enteroviruses have been causing acute flaccid myelitis at a very low rate for many years, misdiagnosed as transverse myelitis, and enterovirus 68 simply happened to become more prevalent in the 2014 season.

The CDC had confirmed 538 cases of enterovirus 68 infection in 43 states. The CDC has determined and submitted to GenBank complete or nearly-complete genomic sequences for three known strains of the virus, which are "genetically related to strains of EV-D68 that were detected in previous years in the United States, Europe, and Asia."

While rates of paralytic symptoms appear to be correlated with the number of respiratory infections, in initial anecdotal reports the cases are not clustered within a family or school, suggesting that the paralysis "per se" is not directly contagious, but arises as a very rare complication of the common respiratory infection.

The list of these diseases depends of the author, but usually are included:

- multiple sclerosis, normally defined by the dissemination in time and space of demyelinating lesions, with two (or sometimes three) clinical presentations:

- Relapsing-Onset multiple sclerosis, the most known and extended variant, normally consisting of two distinct clinical phases (Remitent-Recidivant, RRMS, and Secondary Progressive, SPMS)

- Progressive-Onset MS, most known as Primary progressive MS including a special genetic variant named rapidly progressive multiple sclerosis.

- Optic-spinal MS, or opticospinal, clinical and pathological variant of multiple sclerosis which often include visual symptoms and have a more severe course than typical MS. Though multiple scars (scleroses) are present in CNS, and they comply with the dissemination criteria, and sometimes is classified as clinically definite multiple sclerosis, currently is considered outside the scope of Multiple Sclerosis and inside the scope of Devic's disease, though it is uncertain if this applies to all cases. Also a variant affecting mainly the spinal cord and the cortex has been proposed

- Neuromyelitis optica (NMO), and its associated "spectrum of disorders" (NMOSD), currently considered a common syndrome for at least three separated diseases:, mainly produced by AQP4 autoimmune channelopathy, though other variants exists, some with anti-MOG and some others idiopathic. Some researchers think that there could exist an overlapping between Anti-NMDA receptor encephalitis cases and neuromyelitis optica or acute disseminated encephalomyelitis.

- Anti-MOG associated spectrum, often clinically presented as an anti-MOG autoimmune encephalomyelitis, but can also appear as negative NMO or atypical multiple sclerosis

- CRION (Chronic relapsing inflammatory optic neuritis): A distinct clinical entity from other inflammatory demyelinating diseases including multiple sclerosis (MS), neuromyelitis optica-immunoglobulin G (NMO-IgG) spectrum disease, and idiopathic relapsing optic neuritis.

- Acute disseminated encephalomyelitis or ADEM, a closely related disorder in which a known virus or vaccine triggers autoimmunity against myelin.

- Acute hemorrhagic leukoencephalitis, possibly a variant of Acute disseminated encephalomyelitis

- Balo concentric sclerosis, an unusual presentation of plaques forming concentrenic circles, which can sometimes get better spontaneously.

- Schilder disease or diffuse myelinoclastic sclerosis: is a rare disease that presents clinically as a pseudotumoural demyelinating lesion; and is more common in children.

- Marburg multiple sclerosis, an aggressive form, also known as malignant, fulminant or acute MS.

- Tumefactive multiple sclerosis: lesions whose size is more than 2 cm, with mass effect, oedema and/or ring enhancement

- Solitary sclerosis: This variant has been recently proposed (2012) by Mayo Clinic researches. though it was also reported by other groups more or less at the same time. It is defined as isolated demyelinating lesions which produce a progressive myelopathy similar to primary progressive MS, and is currently considered a synonym for tumefactive multiple sclerosis.

Some inflammatory conditions are associated with the presence of scleroses in the CNS. Optic neuritis (monophasic and recurrent) and Transverse myelitis (monophasic and recurrent)

As MS is an active field for research, the list is not closed or definitive. For example, some diseases like Susac's syndrome (MS has an important vascular component), leukoaraiosis, myalgic encephalomyelitis (aka chronic fatigue syndrome) or autoimmune variants of peripheral neuropathies like Guillain–Barré syndrome or progressive inflammatory neuropathy could be included assuming the autoimmune model. Also Leukodystrophy (which see) and its sub-conditions: Adrenoleukodystrophy and Adrenomyeloneuropathy could be in the list. Venous induced demyelination has also been proposed as a hypothetical MS variant produced by CCSVI.

Recent research has identified some possible new variants, like the possibility to separate primary progressive MS, PPMS, after recent findings seem to point that it is pathologically a very different disease.

Also an OPA1 variant and aKIR4.1 multiple sclerosis variant was reported in 2012 and later reported again, which could be considered a different disease (as Devic disease did before), and can represent up to a 47% of the MS cases. Finally, there exist some reports of an aquaporine-related multiple sclerosis, related to vegetal aquaporine proteins.

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

Neuroborreliosis, also known as Lyme neuroborreliosis (LNB), is a disorder of the central nervous system. A neurological manifestation of Lyme disease, neuroborreliosis is caused by a systemic infection of spirochetes of the genus "Borrelia." Symptoms of the disease include erythema migrans and flu-like symptoms. The microbiological progression of the disease is similar to that of neurosyphilis, another spirochetal infection.

Neuroborreliosis is often preceded by the typical symptoms of Lyme disease, which include erythema migrans and flu-like symptoms such as fever and muscle aches. Neurologic symptoms of neuroborreliosis include the meningoradiculitis (which is more common in European patients), cranial nerve abnormalities, and altered mental status. Sensory findings may also be present. Rarely, a progressive form of encephalomyelitis may occur. In children, symptoms of neuroborreliosis include headache, sleep disturbance, and symptoms associated with increased intracranial pressure, such as papilledema, can occur. Less common childhood symptoms can include meningitis, myelitis, ataxia, and chorea. Ocular Lyme disease has also been reported, as has neuroborreliosis affecting the spinal cord, but neither of these findings are common.

Vascular myelopathy (vascular disease of the spinal cord) refers to an abnormality of the spinal cord in regard to its blood supply. The blood supply is complicated and supplied by two major vessel groups: the posterior spinal arteries and the anterior spinal arteries—of which the Artery of Adamkiewicz is the largest. Both the posterior and anterior spinal arteries run the entire length of the spinal cord and receive anastomotic (conjoined) vessels in many places. The anterior spinal artery has a less efficient supply of blood and is therefore more susceptible to vascular disease. Whilst atherosclerosis of spinal arteries is rare, necrosis (death of tissue) in the anterior artery can be caused by disease in vessels originating from the segmental arteries such as atheroma (arterial wall swelling) or aortic dissection (a tear in the aorta).

Anterior spinal artery syndrome is necrosis of tissue in the anterior spinal artery or its branches. It is characterised by pain which radiates at onset and sudden quadraplegia (paralysis of all four limbs) or paraplegia (paralysis of the lower body). Within days, flaccid limbs become spastic and hyporeflexia (underactive nerve responses) turns into hyperreflexia (overactive nerve responses) and extensor plantar nerve responses. Sensory loss to pain and temperature also occurs up to the level of damage on the spinal cord, as damage to different areas will affect different parts of the body.

In diagnosis, other causes of abrupt paralysis should be excluded such as cord compression, transverse myelitis (inflammation of the spinal cord) and Guillain–Barré syndrome. A specific cause of the infarction should be looked for, such as diabetes, polyarteritis nodosa (inflammatory damage of vessels) or systemic lupus erythematosus. Neurosyphilis is also a known cause. Other causes include:

Treatment is supportive and aims to relieve symptoms. The prognosis is dependent upon individual circumstances and factors.

Upper limb paralysis refers to the loss of function of the elbow and hand. When upper limb function is absent as a result of a spinal cord injury it is a major barrier to regain autonomy. People with tetraplegia should be examined and informed concerning the options for reconstructive surgery of the tetraplegic arms and hands.

There are about 5,000 cervical spinal cord injuries per year in the United States (~1 in 60,000—assuming a population of 300 million), and about 1,000 per year in the UK (also ~1 in 60,000—assuming a population of 60 million). In 2009, it was estimated that the lifetime care of a 25-year-old person rendered with low tetraplegia was about US $1.7 million and with high tetraplegia $3.1 million, and that the total national costs for all SCI's in the United States were US $9.7 billion per year. It currently (2010) costs between $520,000 to $550,000 per year to care for a ventilator dependent person with tetraplegia.

Although there is sometimes a preceding viral infection, or skin or eye trauma, the exact underlying initiator of VKH disease remains unknown. However, VKH is attributed to aberrant T-cell-mediated immune response directed against self-antigens found on melanocytes. Stimulated by interleukin 23 (IL-23), T helper 17 cells and cytokines such as interleukin 17 (IL-17) appear to target proteins in the melanocyte.

Pathophysiology of this disease consists of relaxation of the transverse ligament of the atlanto-axial joint.

Affected individuals are typically 20 to 50 years old. The female to male ratio is 2:1. By definition, there is no history of either surgical or accidental ocular trauma. VKH is more common in Asians, Latinos, Middle Easterners, American Indians, and Mexican Mestizos; it is much less common in Caucasians and in blacks from sub-Saharan Africa.

VKH is associated with a variety of genetic polymorphisms that relate to immune function. For example, VKH has been associated with human leukocyte antigens (HLA) HLA-DR4 and DRB1/DQA1, copy-number variations (CNV) of complement component 4, a variant IL-23R locus and with various other non-HLA genes. HLA-DRB1*0405 in particular appears to play an important susceptibility role.

Treatment includes anti-inflammatory medications and immobilization of the neck in addition to treatment of the offending infectious cause (if any) with appropriate antibiotics. Early treatment is crucial to prevent long-term sequelae. Surgical fusion may be required for residual instability of the joint.