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.

Inflammatory demyelinating diseases (IDDs), sometimes called Idiopathic (IIDDs) because the unknown etiology of some of them, and sometimes known as borderline forms of multiple sclerosis, is a collection of multiple sclerosis variants, sometimes considered different diseases, but considered by others to form a spectrum differing only in terms of chronicity, severity, and clinical course.

Multiple Sclerosis for some people is a syndrome more than a single disease. It can be considered among the acquired demyelinating syndromes with a multiphasic instead of monophasic behaviour. Multiple sclerosis also has a prodromal stage in which an unknown underlying condition, able to damage the brain, is present, but no lesion has still developed.

Symptoms are similar to those in multiple sclerosis and may include dementia, aphasia, seizures, personality changes, poor attention, tremors, balance instability, incontinence, muscle weakness, headache, vomiting, and vision and speech impairment.

Some NMO patients present double positive for autoantibodies to AQP4 and MOG. These patients have MS-like brain lesions, multifocal spine lesions and retinal and optic nerves atrophy.

Symptoms of standard MS consist of both sensory and motor symptoms. The more common symptoms include spasticity, visual loss, difficulty in walking and paresthesia which is a feeling of tickling or numbness of the skin. but symptoms of tumefactive MS are not so clear. They often mimic a variety of other diseases including ischemic stroke, peroneal nerve palsy and intracranial neurologic disease.

Subjects have been reported to suffer from a decreased motor control resulting in a ‘foot drop’, or significantly reduced leg movement. In other cases closer mimicking strokes, subjects may suffer from confusion, dizziness, and weakness in one side of the face. Symptoms also can mimic a neoplasm with symptoms such as headaches, aphasia, and/ or seizures.[13]

There are some differences with normal MS symptoms.

Spasticity is not as in tumefactive cases, because it standard MS it is caused by demyelination or inflammation in the motor areas of the brain or the spinal cord. This upper motor neuron syndrome appears when motor control of skeletal muscles is affected due to damage to the efferent motor pathways. Spasticity is an involuntary muscle movement like an exaggerated stretch reflex, which is when a muscle overcompensates and contracts too much in response to the muscle being stretched. It is believed that spasticity is the result of the lack of inhibitory control on the muscles, an effect of neuronal damage.

Visual loss or disturbances are also different. In standard MS are a result of inflammation of the optic nerve, known as optic neuritis. The effects of optic neuritis can be loss of color perception and worsening vision. Vision loss usually starts off centrally in one eye and may lead to complete loss of vision after a period of time.

The possible cognitive dysfunction is also rare in tumefactive cases. MS patients may show signs of cognitive impairment where there is a reduction in the speed of information processing, a weaker short-term memory and a difficulty in learning new concepts. This cognitive impairment is associated with the loss of brain tissue, known as brain atrophy which is a result of the demyelination process in MS.

About fatigue, most MS patients experience fatigue and this could be a direct result of the disease, depression or sleep disturbances due to MS. It is not clearly understood how MS results in physical fatigue but it is known that the repetitive usage of the same neural pathways results in nerve fiber fatigue that could cause neurological symptoms. Such repeated usage of neural pathways include continuous reading which may result in temporary vision failure.

The disease is more common in Chinese and Filipino populations (both Asiatic) than in caucasoids.

A person with MS can have almost any neurological symptom or sign, with autonomic, visual, motor, and sensory problems being the most common. The specific symptoms are determined by the locations of the lesions within the nervous system, and may include loss of sensitivity or changes in sensation such as tingling, pins and needles or numbness, muscle weakness, blurred vision, very pronounced reflexes, muscle spasms, or difficulty in moving; difficulties with coordination and balance (ataxia); problems with speech or swallowing, visual problems (nystagmus, optic neuritis or double vision), feeling tired, acute or chronic pain, and bladder and bowel difficulties, among others. Difficulties thinking and emotional problems such as depression or unstable mood are also common. Uhthoff's phenomenon, a worsening of symptoms due to exposure to higher than usual temperatures, and Lhermitte's sign, an electrical sensation that runs down the back when bending the neck, are particularly characteristic of MS. The main measure of disability and severity is the expanded disability status scale (EDSS), with other measures such as the multiple sclerosis functional composite being increasingly used in research.

The condition begins in 85% of cases as a clinically isolated syndrome (CIS) over a number of days with 45% having motor or sensory problems, 20% having optic neuritis, and 10% having symptoms related to brainstem dysfunction, while the remaining 25% have more than one of the previous difficulties. The course of symptoms occurs in two main patterns initially: either as episodes of sudden worsening that last a few days to months (called relapses, exacerbations, bouts, attacks, or flare-ups) followed by improvement (85% of cases) or as a gradual worsening over time without periods of recovery (10–15% of cases). A combination of these two patterns may also occur or people may start in a relapsing and remitting course that then becomes progressive later on. Relapses are usually not predictable, occurring without warning. Exacerbations rarely occur more frequently than twice per year. Some relapses, however, are preceded by common triggers and they occur more frequently during spring and summer. Similarly, viral infections such as the common cold, influenza, or gastroenteritis increase their risk. Stress may also trigger an attack. Women with MS who become pregnant experience fewer relapses; however, during the first months after delivery the risk increases. Overall, pregnancy does not seem to influence long-term disability. Many events have been found not to affect relapse rates including vaccination, breast feeding, physical trauma, and Uhthoff's phenomenon.

Several phenotypes (commonly termed "types"), or patterns of progression, have been described. Phenotypes use the past course of the disease in an attempt to predict the future course. They are important not only for prognosis but also for treatment decisions. Currently, the United States National Multiple Sclerosis Society and the Multiple Sclerosis International Federation, describes four types of MS (revised in 2013):

1. Clinically isolated syndrome (CIS)

2. Relapsing-remitting MS (RRMS)

3. Primary progressive MS (PPMS)

4. Secondary progressive MS (SPMS)

Relapsing-remitting MS is characterized by unpredictable relapses followed by periods of months to years of relative quiet (remission) with no new signs of disease activity. Deficits that occur during attacks may either resolve or leave problems, the latter in about 40% of attacks and being more common the longer a person has had the disease. This describes the initial course of 80% of individuals with MS. When deficits always resolve between attacks, this is sometimes referred to as "benign MS", although people will still build up some degree of disability in the long term. On the other hand, the term "malignant multiple sclerosis" is used to describe people with MS having reached significant level of disability in a short period. The relapsing-remitting subtype usually begins with a clinically isolated syndrome (CIS). In CIS, a person has an attack suggestive of demyelination, but does not fulfill the criteria for multiple sclerosis. 30 to 70% of persons experiencing CIS later develop MS.

Primary progressive MS occurs in approximately 10–20% of individuals, with no remission after the initial symptoms. It is characterized by progression of disability from onset, with no, or only occasional and minor, remissions and improvements. The usual age of onset for the primary progressive subtype is later than of the relapsing-remitting subtype. It is similar to the age that secondary progressive usually begins in relapsing-remitting MS, around 40 years of age.

Secondary progressive MS occurs in around 65% of those with initial relapsing-remitting MS, who eventually have progressive neurologic decline between acute attacks without any definite periods of remission. Occasional relapses and minor remissions may appear. The most common length of time between disease onset and conversion from relapsing-remitting to secondary progressive MS is 19 years.

Other, unusual types of MS have been described; these include Devic's disease, Balo concentric sclerosis, Schilder's diffuse sclerosis, and Marburg multiple sclerosis. There is debate on whether they are MS variants or different diseases. Multiple sclerosis behaves differently in children, taking more time to reach the progressive stage. Nevertheless, they still reach it at a lower average age than adults usually do.

The demyelinating diseases of the peripheral nervous system include:

- Guillain–Barré syndrome and its chronic counterpart, chronic inflammatory demyelinating polyneuropathy

- Anti-MAG peripheral neuropathy

- Charcot–Marie–Tooth disease and its counterpart Hereditary neuropathy with liability to pressure palsy

- Copper deficiency associated conditions (peripheral neuropathy, myelopathy, and rarely optic neuropathy)

- Progressive inflammatory neuropathy

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.

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.

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.

The demyelinating disorders of the central nervous system include:

- Myelinoclastic disorders, in which myelin is attacked by external substances

- standard multiple sclerosis, Devic's disease and other disorders with immune system involvement called inflammatory demyelinating diseases.

- Leukodystrophic disorders, in which myelin is not properly produced:

- CNS neuropathies like those produced by vitamin B12 deficiency

- Central pontine myelinolysis

- Myelopathies like tabes dorsalis (syphilitic myelopathy)

- leukoencephalopathies like progressive multifocal leukoencephalopathy

- Leukodystrophies

These disorders are normally associated also with the conditions optic neuritis and transverse myelitis, which are inflammatory conditions, because inflammation and demyelination are frequently associated. Some of them are idiopathic and for some others the cause has been found, like some cases of neuromyelitis optica.

Symptoms can develop over several weeks to months. Symptoms depend on location of damage in the brain and the degree of damage. The most prominent symptoms are "clumsiness, progressive weakness and visual, speech, and sometimes personality changes"

The lesions affecting the parietal and occipital lobes can lead to a phenomenon known as alien hand syndrome.

It took its name from Otto Marburg. It can be diagnosed "in vivo" with an MRI scan.

If Marburg disease occurs in the form of a single large lesion, it can be radiologically indistinguishable from a brain tumor or abscess. It is usually lethal, but it has been found to be responsive to Mitoxantrone and Alemtuzumab, and it has also been responsive to autologous stem cell transplantation. Recent evidence shows that Marburg's presents a heterogeneous response to medication, as does standard MS.

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.

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.

Progressive multifocal leukoencephalopathy (PML) is a rare and usually fatal viral disease characterized by progressive damage ("-pathy") or inflammation of the white matter ("leuko-") of the brain ("-encephalo-") at multiple locations ("multifocal"). It is caused by the JC virus, which is normally present and kept under control by the immune system. JC virus is harmless except in cases of weakened immune systems. In general, PML has a mortality rate of 30–50 percent in the first few months and those who survive can be left with varying degrees of neurological disabilities.

PML occurs almost exclusively in patients with severe immune deficiency, most commonly among patients with acquired immune deficiency syndrome (AIDS), but people on chronic immunosuppressive medications including chemotherapy are also at increased risk of PML, such as patients with transplants, Hodgkin's lymphoma, multiple sclerosis, psoriasis and other autoimmune diseases.

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

In contrast to amyotrophic lateral sclerosis or primary lateral sclerosis, PMA is distinguished by the "absence" of:

- brisk reflexes

- spasticity

- Babinski's sign

- Emotional lability

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.

As a result of lower motor neurone degeneration, the symptoms of PMA include:

- atrophy

- fasciculations

- muscle weakness

Some patients have symptoms restricted only to the arms or legs (or in some cases just one of either). These cases are referred to as "Flail Arm" (FA) or "Flail Leg" (FL) and are associated with a better prognosis.

A hereditary CNS demyelinating disease is a demyelinating central nervous system disease that is primarily due to an inherited genetic condition. (This is in contrast to autoimmune demyelinating conditions, such as multiple sclerosis, or conditions such as central pontine myelinolysis that are associated with acute acquired insult.)

Examples include:

- Alexander disease

- Canavan disease

- Krabbe disease

- leukoencephalopathy with vanishing white matter

- megalencephalic leukoencephalopathy with subcortical cysts

- metachromatic leukodystrophy

- X-linked adrenoleukodystrophy

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.

Anterior horn disease is one of a number of medical disorders affecting the anterior horn of the spinal cord. Anterior horn diseases include spinal muscular atrophy, poliomyelitis and amyotrophic lateral sclerosis.