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.

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.

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.

A preceding antigenic challenge can be identified in approximately two-thirds of people. Viral infections thought to induce ADEM include influenza virus, enterovirus, measles, mumps, rubella, varicella zoster, Epstein Barr virus, cytomegalovirus, herpes simplex virus, hepatitis A, and coxsackievirus; while the bacterial infections include Mycoplasma pneumoniae, Borrelia burgdorferi, Leptospira, and beta-hemolytic Streptococci. The only vaccine proven to induce ADEM is the Semple form of the rabies vaccine, but hepatitis B, pertussis, diphtheria, measles, mumps, rubella, pneumococcus, varicella, influenza, Japanese encephalitis, and polio vaccines have all been implicated. The majority of the studies that correlate vaccination with ADEM onset use small samples or case studies. Large scale epidemiological studies (e.g., of MMR vaccine or smallpox vaccine) do not show increased risk of ADEM following vaccination. In rare cases, ADEM seems to follow from organ transplantation. An upper bound for the risk of ADEM from measles vaccination, if it exists, can be estimated to be 10 per million, which is far lower than the risk of developing ADEM from an actual measles infection, which is about 1 per 1,000 cases. For a rubella infection, the risk is 1 per 5,000 cases. Some early vaccines, later shown to have been contaminated with host animal CNS tissue, had ADEM incident rates as high as 1 in 600.

In 1982 Lewis et al reported a group of patients with a chronic asymmetrical sensorimotor neuropathy mostly affecting the arms with multifocal involvement of peripheral nerves. Also in 1982 Dyck "et al" reported a response to prednisolone to a condition they referred to as chronic inflammatory demyelinating polyradiculoneuropathy. Parry and Clarke in 1988 described a neuropathy which was later found to be associated with IgM autoantibodies directed against GM1 gangliosides. This latter condition was later termed multifocal motor neuropathy This distinction is important because multifocal motor neuropathy responds to intravenous globulin alone while chronic inflammatory demyelinating polyneuropathy responds to intravenous globulin, steroids and plasma exchanges. It has been suggested that multifocal motor neuropathy is distinct from chronic inflammatory demyelinating polyneuropathy and that Lewis-Summer syndrome is a distinct variant type of chronic inflammatory demyelinating polyneuropathy.

The Lewis-Summer form of this condition is considered a rare disease with only 50 cases reported up to 2004. A total of 90 cases had been reported by 2009

Chronic inflammatory demyelinating polyneuropathy, also known as Vidaurri's disease, is believed to be due to immune cells, which normally protect the body from foreign infection, incorrectly attacking the nerves in the body instead. As a result, the affected nerves fail to respond, or respond only weakly, and on occasion, inordinately, to stimuli, causing numbing, tingling, pain, progressive muscle weakness, loss of deep tendon reflexes (areflexia), fatigue, and abnormal sensations. The likelihood of progression of the disease is high.

CIDP is under-recognized and under-treated due to its heterogeneous presentation (both clinical and electrophysiological) and the limitations of clinical, serologic, and electrophysiologic diagnostic criteria. Despite these limitations, early diagnosis and treatment is important in preventing irreversible axonal loss and improving functional recovery.

Lack of awareness and treatment of CIDP is also due to limitations of clinical trials. Although there are stringent research criteria for selecting patients to clinical trials, there are no generally agreed-on clinical diagnostic criteria for CIDP due to its different presentations in symptoms and objective data. Application of the present research criteria to routine clinical practice often miss the diagnosis in a majority of patients, and patients are often left untreated despite progression of their disease.

Full recovery is seen in 50 to 70% of cases, ranging to 70 to 90% recovery with some minor residual disability (typically assessed using measures such as mRS or EDSS), average time to recover is one to six months. The mortality rate may be as high as 5%. Poorer outcomes are associated with unresponsiveness to steroid therapy, unusually severe neurological symptoms, or sudden onset. Children tend to have more favorable outcomes than adults, and cases presenting without fevers tend to have poorer outcomes. The latter effect may be due to either protective effects of fever, or that diagnosis and treatment is sought more rapidly when fever is present.

ADEM can progress to MS. It will be considered MS if some lesions appear in different times and brain areas

Encephalomyelitis is inflammation of the brain and spinal cord. Various types of encephalomyelitis include:

- "Acute disseminated encephalomyelitis" or "postinfectious encephalomyelitis", a demyelinating disease of the brain and spinal cord, possibly triggered by viral infection.

- "Encephalomyelitis disseminata", a synonym for multiple sclerosis.

- "AntiMOG associated encephalomyelitis", one of the underlying conditions for the phenotype neuromyelitis optica and in general all the spectrum of MOG autoantibody-associated demyelinating diseases.

- "Equine encephalomyelitis", also called "equine encephalitis", a potentially fatal mosquito-borne viral disease that infects horses and humans.

- "Myalgic encephalomyelitis", a disease involving presumed inflammation of the central nervous system with symptoms of muscle pain and fatigue; the term has sometimes been used interchangeably with "chronic fatigue syndrome", though there is still controversy over the distinction.

- "Experimental autoimmune encephalomyelitis" (EAE), an animal model of brain inflammation.

- Progressive encephalomyelitis with rigidity and myoclonus (PERM) – A kind of stiff person syndrome.

- AIDS related encephalomyelitis, caused by opportunistic Human T-lymphotropic virus type III (HTLV-III) infection.

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

The causes of polyneuropathy can be divided into hereditary and acquired and are therefore as follows:

- "Inherited" -are hereditary motor neuropathies, Charcot–Marie–Tooth disease, and hereditary neuropathy with liability to pressure palsy

- "Acquired" -are diabetes mellitus, vascular neuropathy, alcohol abuse, and Vitamin B12 deficiency

Among the signs/symptoms of polyneuropathy, which can be divided (into sensory and hereditary) and are consistent with the following:

- "Sensory polyneuropathy" - ataxia, numbness, muscle wasting and paraesthesiae.

- "Hereditary polyneuropathy" - scoliosis and hammer toes

Balo concentric sclerosis is a disease in which the white matter of the brain appears damaged in concentric layers, leaving the axis cylinder intact. It was described by Joszef Balo who initially named it "leuko-encephalitis periaxialis concentrica" from the previous definition, and it is currently considered one of the borderline forms of multiple sclerosis.

Balo concentric sclerosis is a demyelinating disease similar to standard multiple sclerosis, but with the particularity that the demyelinated tissues form concentric layers. Scientists used to believe that the prognosis was similar to Marburg multiple sclerosis, but now they know that patients can survive, or even have spontaneous remission and asymptomatic cases.

It is also common that the clinical course is primary progressive, but a relapsing-remitting course has been reported.

It seems that the course gets better with prednisone therapy, although evidence of this is anecdotal and such conclusions are difficult to accept given that there are cases where patients spontaneously recover whether the patient was on steroid therapy or not.

Experimental autoimmune encephalomyelitis, sometimes experimental allergic encephalomyelitis (EAE) is an animal model of brain inflammation. It is an inflammatory demyelinating disease of the central nervous system (CNS). It is mostly used with rodents and is widely studied as an animal model of the human CNS demyelinating diseases, including multiple sclerosis and acute disseminated encephalomyelitis (ADEM). EAE is also the prototype for T-cell-mediated autoimmune disease in general.

EAE was motivated by observations during the convalescence from viral diseases by Thomas M. Rivers, D. H. Sprunt and G. P. Berry in 1933. Their findings upon a transfer of inflamed patient tissue to primates was published in the "Journal of Experimental Medicine". An acute monophasic illness, it has been suggested that EAE is far more similar to ADEM than MS.

EAE can be induced in a number of species, including mice, rats, guinea pigs, rabbits and primates. The most commonly used antigens in rodents are spinal cord homogenate (SCH), purified myelin, myelin protein such as MBP, PLP, and MOG, or peptides of these proteins, all resulting in distinct models with different disease characteristics regarding both immunology and pathology. It may also be induced by the passive transfer of T cells specifically reactive to these myelin antigens.

Depending on the antigen used and the genetic make-up of the animal, rodents can display a monophasic bout of EAE, a relapsing-remitting form, or chronic EAE. The typical susceptible rodent will debut with clinical symptoms around two weeks after immunization and present with a relapsing-remitting disease. The archetypical first clinical symptom is weakness of tail tonus that progresses to paralysis of the tail, followed by a progression up the body to affect the hind limbs and finally the forelimbs. However, similar to MS, the disease symptoms reflect the anatomical location of the inflammatory lesions, and may also include emotional lability, sensory loss, optic neuritis, difficulties with coordination and balance (ataxia), and muscle weakness and spasms. Recovery from symptoms can be complete or partial and the time varies with symptoms and disease severity. Depending on the relapse-remission intervals, rats can have up to 3 bouts of disease within an experimental period.

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

The cause of MS is unknown; however, it is believed to occur as a result of some combination of genetic and environmental factors such as infectious agents. Theories try to combine the data into likely explanations, but none has proved definitive. While there are a number of environmental risk factors and although some are partly modifiable, further research is needed to determine whether their elimination can prevent MS.

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.

MS is more common in people who live farther from the equator, although exceptions exist. These exceptions include ethnic groups that are at low risk far from the equator such as the Samis, Amerindians, Canadian Hutterites, New Zealand Māori, and Canada's Inuit, as well as groups that have a relatively high risk close to the equator such as Sardinians, inland Sicilians, Palestinians and Parsis. The cause of this geographical pattern is not clear. While the north-south gradient of incidence is decreasing, as of 2010 it is still present.

MS is more common in regions with northern European populations and the geographic variation may simply reflect the global distribution of these high-risk populations. Decreased sunlight exposure resulting in decreased vitamin D production has also been put forward as an explanation. A relationship between season of birth and MS lends support to this idea, with fewer people born in the northern hemisphere in November as compared to May being affected later in life. Environmental factors may play a role during childhood, with several studies finding that people who move to a different region of the world before the age of 15 acquire the new region's risk to MS. If migration takes place after age 15, however, the person retains the risk of their home country. There is some evidence that the effect of moving may still apply to people older than 15.

Many health conditions can cause autonomic neuropathy. Some common causes of autonomic neuropathy include:

- Diabetes, which is the most common cause of autonomic neuropathy, can gradually cause nerve damage throughout the body.

- Injury to nerves caused by surgery or radiation to the neck.

- Treatment with certain medications, including some drugs used in cancer chemotherapy.

- Abnormal protein buildup in organs (amyloidosis), which affects the organs and the nervous system.

- Other chronic illnesses, such as Parkinson's disease, multiple sclerosis and some types of dementia.

- Autonomic neuropathy may also be caused by an abnormal attack by the immune system that occurs as a result of some cancers (paraneoplastic syndrome).

- Certain infectious diseases. Some viruses and bacteria, such as botulism, Lyme disease and HIV, can cause autonomic neuropathy.

- Inherited disorders. Certain hereditary disorders can cause autonomic neuropathy.

- Autoimmune diseases, in which the immune system attacks and damages parts of the body, including the nerves. Examples include Sjogren's syndrome, systemic lupus erythematosus, rheumatoid arthritis and celiac disease. Guillain-Barre syndrome is an autoimmune disease that happens rapidly and can affect autonomic nerves.

Over 40 laboratory tests were initially conducted to rule out various pathogens and environmental toxins. These tests were used to try to identify potential viruses carried by humans, pigs, or both, including rotoviruses, adenoviruses, hepatitis A, and hepatitis E. They also tried to identify bacteria such as salmonella and escherichia coli (e. coli), and parasites such as Giardia and cryptosporidium that could be causing the symptoms. All were ruled out.

Neurodegenerative diseases were considered specifically because of the similarity of symptoms and animal involvement thus included investigation of prion associated diseases such as bovine spongiform encephalopathy (BSE), chronic wasting disease (CWD), and variant Creutzfeldt–Jakob disease (vCJD). These all have highly transmissible pathogenic agents that induce brain damage. Since no pathogenic agent had been found, these diseases were ruled out as being related.

Next two very similar neuropathies were ruled out. Guillain–Barré syndrome (GBS) induces an acute autoimmune response which affects the Schwann cells in the peripheral nervous system. GBS is usually triggered by an infection that causes weakness and tingling that may lead to muscle loss. This condition may be life-threatening if muscle atrophy ascends to affect the pulmonary or cardiac systems. So far, no infectious agents have been found that relate to the current disease, progressive infammatory neuropathy. They looked at chronic inflammatory demyelinating polyneuropathy (CIDP) which is characterized by progressive weakness and sensory impairment in the arms and legs. Damage occurs to the myelin sheath in the peripheral nervous system. As doctors at the Mayo Clinic were beginning to note, the problem they were seeing in progressive inflammatory neuropathy was occurring in the spinal nerve roots.

Infectious diseases are transmitted in several ways. Some of these infections may affect the brain or spinal cord directly. Generally, an infection is a disease that is caused by the invasion of a microorganism or virus.

An initial comprehensive study of 24 known cases was conducted by multiple doctors from various disciplines at the Mayo Clinic. They identified the cause of this neurological disease to be occupational exposure to aerosolized pig neural tissue. Investigators from the Minnesota Department of Health (MDH) simultaneously determined that the 70 ppsi pressure used to liquefy and extract the pig brains caused the aerosolization of the pig neural tissue, sending it into the air in a fine mist. The workers closest in proximity to the "head" table, the area in the plant where high pressured air was used to evacuate the brain tissue from the pig's skull, were the most likely to be affected. The aerosolized mist was inhaled and readily absorbed into the workers' mucus membranes. The pig neural tissue was recognized by their systems as foreign and an immune response was initiated. The pig antigen was found most prominently in the nerve roots of the spine which were also swollen. Researchers determined that the irritation was due to the voltage-gated potassium channels being blocked. They identified 125 1-α-dendrotoxin as the antagonist that binds to and blocks the channels, causing an intracellular build-up of potassium ions which causes inflammation and irritation, and consequently, hyper-excitability in the peripheral nervous system. It is this hyper-excitability that leads to the tingling, numbness, pain, and weakness.

Researchers from the Mayo Clinic developed a mouse model that received twice daily liquefied pig neural tissue intranasally to replicate the symptoms that the workers were experiencing. Physiological testing indicated signature antibodies in the mouse model at 100% in potassium channel antibodies and myelin basic antibodies, and 91% in calcium channel antibodies. This model allowed the researchers to decipher what was causing these neurological symptoms. It was found that the potassium channels were being blocked so that inflammation was occurring at the nerve root and causing hyper-excitability down the peripheral nerves.

Because the cause of Behçet's disease is unknown, the cause responsible for neuro-Behçet's disease is unknown as well. Inflammation starts mainly due to immune system failure. However, no one knows what factors trigger the initiation of auto-immune disease like inflammation. Because the cause is unknown, it is impossible to eliminate or prevent the source that causes the disease. Therefore, treatments are focused on how to suppress the symptoms that hinders daily life activities.

In one study of 387 Behçet's disease (BD) patients that has been done for 20 years, 13% of men with BD developed to NBD and 5.6% of women developed to NBD.

Combining all statistical reports, approximately 9.4% (43 of 459) BD patients advanced to NBD. In addition, men were 2.8 times more likely to experience NBD than women. This fact indicates possible gender-based pathology.

In speaking about age of NBD patients, the general range was between 20 and 40. NBD patients with age less than 10 or more than 50 were very uncommon.