Extensive pathological and biochemical tests were performed, however the cause was found by studying a small population in which mutations in the eIF2B gene were found. No effective systemic studies have been conducted to determine the incidence around the world, but through the studies conducted thus far, it appears to be more prevalent in the white populations. VWM appears to have a lower number of cases in the Middle East, and Turkey has not yet had a reported case. Its prevalence is limited by the physician’s ability to identify the disease. As of 2006, more than 200 people have been identified with VWM, many of whom were originally diagnosed with an unclassified leukodystrophy.

Preventing or delaying premature birth is considered the most important step in decreasing the risk of PVL. Common methods for preventing a premature birth include self-care techniques (dietary and lifestyle decisions), bed rest, and prescribed anti-contraction medications. Avoiding premature birth allows the fetus to develop further, strengthening the systems affected during the development of PVL.

An emphasis on prenatal health and regular medical examinations of the mother can also notably decrease the risk of PVL. Prompt diagnosis and treatment of maternal infection during gestation reduces the likelihood of large inflammatory responses. Additionally, treatment of infection with steroids (especially in the 24–34 weeks of gestation) have been indicated in decreasing the risk of PVL.

It has also been suggested that avoiding maternal cocaine usage and any maternal-fetal blood flow alterations can decrease the risk of PVL. Episodes of hypotension or decreased blood flow to the infant can cause white matter damage.

There is currently no effective treatment or cure for PSP, although some of the symptoms can respond to nonspecific measures. The average age at symptoms onset is 63 and survival from onset averages 7 years with a wide variance. Pneumonia is a frequent cause of death.

Transneuronal degeneration is the death of neurons resulting from the disruption of input from or output to other nearby neurons. It is an active excitotoxic process when a neuron is overstimulated by a neurotransmitter (most commonly glutamate) causing the dysfunction of that neuron (either damaging it or killing it) which drives neighboring neurons into metabolic deficit, resulting in rapid, widespread loss of neurons. This can be either anterograde or retrograde, indicating the direction of the degeneration relative to the original site of damage (see types). There are varying causes for transneuronal degeneration such as brain lesions, disconnection syndromes, respiratory chain deficient neuron interaction, and lobectomies. Although there are different causes, transneuronal degeneration generally results in the same effects (whether they be cellular, dendritic, or axonal) to varying degrees. Transneuronal degeneration is thought to be linked to a number of diseases, most notably Huntington's disease and Alzheimer's disease, and researchers recently have been performing experiments with monkeys and rats, monitoring lesions in different parts of the body to study more closely how exactly the process works.

There are no treatments, only precautions which can be taken, mainly to reduce trauma to the head and avoiding physiological stress. Melatonin has been shown to provide cytoprotective traits to glial cells exposed to stressors such as excitotoxicity and oxidative stress. These stressors would be detrimental to cells with a genetically reduced activity of protein eIF2B. However, research connecting these ideas have not been conducted yet.

The cause of PSP is unknown. Fewer than 1% of those with PSP have a family member with the same disorder. A variant in the gene for tau protein called the H1 haplotype, located on chromosome 17, has been linked to PSP. Nearly all people with PSP received a copy of that variant from each parent, but this is true of about two-thirds of the general population. Therefore, the H1 haplotype appears to be necessary but not sufficient to cause PSP. Other genes, as well as environmental toxins, are being investigated as other possible contributors to the cause of PSP.

Although no treatments have been approved for use in human PVL patients, a significant amount of research is occurring in developing treatments for protection of the nervous system. Researchers have begun to examine the potential of synthetic neuroprotection to minimize the amount of lesioning in patients exposed to ischemic conditions.

Behr syndrome is characterized by the association of early-onset optic atrophy with spinocerebellar degeneration resulting in ataxia, pyramidal signs, peripheral neuropathy and developmental delay.

Although it is an autosomal recessive disorder, heterozygotes may still manifest much attenuated symptoms. Autosomal dominant inheritance also being reported in a family. Recently a variant of OPA1 mutation with phenotypic presentation like Behr syndrome is also described. Some reported cases have been found to carry mutations in the OPA1, OPA3 or C12ORF65 genes which are known causes of pure optic atrophy or optic atrophy complicated by movement disorder.

Friedreich's ataxia is an autosomal recessive inherited disease that causes progressive damage to the nervous system. It manifests in initial symptoms of poor coordination such as gait disturbance; it can also lead to scoliosis, heart disease and diabetes, but does not affect cognitive function. The disease is progressive, and ultimately a wheelchair is required for mobility. Its incidence in the general population is roughly 1 in 50,000.

The particular genetic mutation (expansion of an intronic GAA triplet repeat in the FXN gene) leads to reduced expression of the mitochondrial protein frataxin. Over time this deficiency causes the aforementioned damage, as well as frequent fatigue due to effects on cellular metabolism.

The ataxia of Friedreich's ataxia results from the degeneration of nervous tissue in the spinal cord, in particular sensory neurons essential (through connections with the cerebellum) for directing muscle movement of the arms and legs. The spinal cord becomes thinner and nerve cells lose some of their myelin sheath (the insulating covering on some nerve cells that helps conduct nerve impulses).

The condition is named after the German physician Nikolaus Friedreich, who first described it in the 1860s.

Transneuronal degeneration can be grouped into two general categories: anterograde and retrograde.

Friedreich's ataxia is the most prevalent inherited ataxia, affecting about 1 in 50,000 people in the United States. Males and females are affected equally. The estimated carrier prevalence is 1:110.

A 1984 Canadian study was able to trace 40 cases of classical Friedreich's disease from 14 French-Canadian kindreds previously thought to be unrelated to one common ancestral couple arriving in New France in 1634: Jean Guyon and Mathurine Robin.

Of the millions experiencing strokes worldwide, over 30,000 in the United States alone have developed some form of Dejerine–Roussy syndrome. 8% of all stroke patients will experience central pain syndrome, with 5% experiencing moderate to severe pain. The risk of developing Dejerine–Roussy syndrome is higher in older stroke patients, about 11% of stroke patients over the age of 80.

From recent studies, de novo and inherited mutations in the gene "COL4A1", suggesting genetic predisposition within the family, that encodes type IV collagen α1 chain has shown to be associated with and present in patients with porencephaly. "COL4A1" mutation causes a variety of phenotypes, including porencephaly, infantile hemiplegia, and cerebral small vessel diseases involving both stroke and infarction. Abnormal gene expression of "COL4A1" can contribute to the development of porencephaly. "COL4A1" gene expresses a type IV collagen (basement protein) that is present in all tissue and blood vessels and is extremely important for the structural stability of vascular basement membranes. The "COL4A1" protein provides a strong layer around blood vessels. The mutation can weaken the blood vessels within the brain, elevating the probability of a hemorrhage, and eventually promoting internal bleeding then leading to porencephaly during neurodevelopment of infantile stage. Therefore, the formation of cavities can be a result of hemorrhages which promote cerebral degeneration. In a mouse model, mouse with "COL4A1" mutations displayed cerebral hemorrhage, porencephaly, and abnormal development of vascular basement membranes, such as uneven edges, inconsistent shapes, and highly variable thickness. Purposely causing a mutation in the "COL4A1" gene caused several mouse to develop cerebral hemorrhage and porencephaly-like diseases. Though, there is no direct correlation between mutations of the "COL4A1" gene, it appears that it has an influential effect on the development of porencephaly.

Another genetic mutation, "factor V G1691A" mutation, has been reported to show possible association to the development of porencephaly. A mutation in "factor V G1691A" increases the risk of thrombosis, blood clots, in neonates, infants, and children. Therefore, 76 porencephalic and 76 healthy infants were investigated for "factor V G1691A" mutation along with other different prothrombotic risk factors. The results indicated that there was higher prevalence of the "factor V G1691A" mutation in the porencephalic patient group. The prediction that childhood porencephaly is caused by hypercoagulable state, a condition where one has a higher chance of developing blood clots, was supported by the significance of the "factor V G1691A" mutation. Also, pregnant women in hypercoagulable state can cause the fetus to have the same risks, therefore possibly causing fetal loss, brain damage, lesions, and infections that lead to porencephaly. However, other different prothrombotic risk factors individually did not reach statistical significance to link it to the development of porencephaly, but a combination of multiple prothrombotic risk factors in the porencephaly group was significant. Overall, "factor V G1691A" mutation has been linked to the development of porencephaly. However, this one mutation is not the cause of porencephaly, and whether further prothrombiotic risk factors are associated with porencephaly still remains unknown.

Chorea is another condition which results from damage to the basal ganglia. Similar to athetosis, it results from mutations affecting the pallidum inhibition of the thalamus as well as increased dopaminergic activity at the level of the striatum. Considering the etiology of both disorders are fairly similar, it comes as no surprise that chorea and athetosis can and usually do occur together in a condition called choreoathetosis.

Athetosis is a commonly occurring symptom in the disease cerebral palsy. Of all people with the disease, between 16% and 25% of them actually exhibit the symptom of athetosis. A component of this is the finding that most often the symptoms that involve athetosis occur as a part of choreoathetosis as opposed to athetosis alone.

It is also noteworthy that the presence of athetosis in cerebral palsy (as well as other conditions) causes a significant increase in a person’s basal resting metabolic rate. It has been observed that those who have cerebral palsy with athetosis require approximately 500 more Calories per day than their non-cerebral palsy non-athetoid counterpart.

Onset : Early childhood

Progression: Chronic progressive

Clinical: Cerebellar ataxia plus syndrome / Optic Atrophy Plus Syndrome

Ocular: Optic atrophy, nystagmus, scotoma, and bilateral retrobulbar neuritis.

Other: Mental retardation, myoclonic epilepsy, spasticity, and posterior column sensory loss. Tremor in some cases.

Musculoskeletal

Contractures, lower limbs, Achilles tendon contractures, Hamstring contractures, Adductor longus contractures

Systemic

Hypogonadotrophic hypogonadism.

In utero exposure to cocaine and other street drugs can lead to porencephaly.

Parinaud's Syndrome results from injury, either direct or compressive, to the dorsal midbrain. Specifically, compression or ischemic damage of the mesencephalic tectum, including the superior colliculus adjacent oculomotor (origin of cranial nerve III) and Edinger-Westphal nuclei, causing dysfunction to the motor function of the eye.

Classically, it has been associated with three major groups:

1. Young patients with brain tumors in the pineal gland or midbrain: pinealoma (intracranial germinomas) are the most common lesion producing this syndrome.

2. Women in their 20s-30s with multiple sclerosis

3. Older patients following stroke of the upper brainstem

However, any other compression, ischemia or damage to this region can produce these phenomena: obstructive hydrocephalus, midbrain hemorrhage, cerebral arteriovenous malformation, trauma and brainstem toxoplasmosis infection. Neoplasms and giant aneurysms of the posterior fossa have also been associated with the midbrain syndrome.

Vertical supranuclear ophthalmoplegia has also been associated with metabolic disorders, such as Niemann-Pick disease, Wilson's disease, kernicterus, and barbiturate overdose.

It is not possible to make a generalised prognosis for development due to the variability of causes, as mentioned above, the differing types of symptoms and cause. Each case must be considered individually.

The prognosis for children with idiopathic West syndrome are mostly more positive than for those with the cryptogenic or symptomatic forms. Idiopathic cases are less likely to show signs of developmental problems before the attacks begin, the attacks can often be treated more easily and effectively and there is a lower relapse rate. Children with this form of the syndrome are less likely to go on to develop other forms of epilepsy; around two in every five children develop at the same rate as healthy children.

In other cases, however, treatment of West syndrome is relatively difficult and the results of therapy often dissatisfying; for children with symptomatic and cryptogenic West syndrome, the prognosis is generally not positive, especially when they prove resistant to therapy.

Statistically, 5 out of every 100 children with West syndrome do not survive beyond five years of age, in some cases due to the cause of the syndrome, in others for reasons related to their medication. Only less than half of all children can become entirely free from attacks with the help of medication. Statistics show that treatment produces a satisfactory result in around three out of ten cases, with only one in every 25 children's cognitive and motoric development developing more or less normally.

A large proportion (up to 90%) of children suffer severe physical and cognitive impairments, even when treatment for the attacks is successful. This is not usually because of the epileptic fits, but rather because of the causes behind them (cerebral anomalies or their location or degree of severity). Severe, frequent attacks can (further) damage the brain.

Permanent damage often associated with West syndrome in the literature include cognitive disabilities, learning difficulties and behavioural problems, cerebral palsy (up to 5 out of 10 children), psychological disorders and often autism (in around 3 out of 10 children). Once more, the cause of each individual case of West syndrome must be considered when debating cause and effect.

As many as 6 out of 10 children with West syndrome suffer from epilepsy later in life. Sometimes West syndrome turns into a focal or other generalised epilepsy. Around half of all children develop Lennox-Gastaut syndrome.

Currently, no research has shown a higher prevalence of most leukodsytrophy types in any one place around the world. There is, however, a higher prevalence of the Canavan disease in the Jewish population for unknown reasons. 1 in 40 individuals of Ashkenazi Jewish descent are carriers of Canavan disease. This estimates to roughly 2.5%. Additionally, due to an autosomal recessive inheritance patterns, there is no significant difference found between affected males and affected females for most types of leukodystrophy including, but not limited to, metachromatic leukodystrophy, Krabbe disease, Canavan disease, and Alexander disease. The one exception to this is any type of leukodystrophy carried on a sex chromosome, such as X-linked adrenoleukodystrophy, which is carried on the X-chromosome. Because of the inheritance pattern of X-linked diseases, males are more often affected by this type of leukodystrophy, although female carriers are often symptomatic, though not as severely so as males. To date, there have been no found cases of a leukodystrophy carried on the Y chromosome.

West syndrome appears in 1% to 5% of infants with Down syndrome. This form of epilepsy is relatively difficult to treat in children who do not have the chromosomal abnormalities involved in Down syndrome. However, in children with Down syndrome, the syndrome is often far more mild, and the children often react better to medication. The German Down Syndrom InfoCenter noted in 2003 that what was normally a serious epilepsy was in such cases often a relatively benign one.

EEG records for children with Down syndrome are often more symmetrical with fewer unusual findings. Although not all children can become entirely free from attacks with medication, children with Down syndrome are less likely to go on to develop Lennox-Gastaut syndrome or other forms of epilepsy than those without additional hereditary material on the 21st chromosome. The reason why it is easier to treat children with Down syndrome is not known.

If, however, a child with Down syndrome has seizures that are difficult to control, the child should be accessed for autistic spectrum disorder.

The eye findings of Parinaud's Syndrome generally improve slowly over months, especially with resolution of the causative factor; continued resolution after the first 3–6 months of onset is uncommon. However, rapid resolution after normalization of intracranial pressure following placement of a ventriculoperitoneal shunt has been reported.

Treatment is primarily directed towards etiology of the dorsal midbrain syndrome. A thorough workup, including neuroimaging is essential to rule out anatomic lesions or other causes of this syndrome. Visually significant upgaze palsy can be relieved with bilateral inferior rectus recessions. Retraction nystagmus and convergence movement are usually improved with this procedure as well.

The most common cause of diplegia in the legs is Cerebral Palsy. Paralysis of the legs may also be caused by trauma, injury, or genetics but this is very rare

The treatment for facial diplegia depends on the underlying cause. Some causes are usually treatable such as infectious, toxic, and vascular by treating the main problem first. After the underlying problem is cured, the facial paralysis usually will go away.

Specific types of leukodystrophies include the following with their respective ICD-10 codes when available:

- (E71.3) Adrenomyeloneuropathy

- (E75.2) Alexander disease

- (E75.5) Cerebrotendineous xanthomatosis

- Hereditary CNS demyelinating disease

- (E75.2) Krabbe disease

- (E75.2) Metachromatic leukodystrophy

- (E75.2) Pelizaeus–Merzbacher disease

- (E75.2) Canavan disease

- (G93.49) Leukoencephalopathy with vanishing white matter

- (E71.3) Adrenoleukodystrophy

- (G60.1) Refsum disease