The Leukoencephalopathy Is the name given to any disorder that affects the white matter of the brain, regardless of its causes.
The white substance or white matter, is a part of the Central Nervous System Whose nerve cells are covered with a substance called myelin.
Myelin is composed of layers of Lipoproteins That promote the transmission of nerve impulses throughout the Neurons . That is, it causes information to travel much faster in our brain.
It can happen that, due to hereditary factors, myelin once developed, begins to degenerate (what is denominated as Leukodystrophies ). Whereas, those conditions in which problems occur in the formation of myelin are called Demyelinating diseases.
However, despite scientific advances, it appears that more than 50% of patients with hereditary leukoencephalopathy remain undiagnosed. That is why new types and more accurate ways of diagnosing them are being discovered.
Leukoencephalopathy can also arise from acquired causes such as infections, neoplasms or toxins; And can appear at any time in life, from neonatal stages to adulthood.
Whatever its cause, this gives rise to a variety of symptoms such as cognitive deficits, Convulsions , Y ataxia . In addition, these can remain static, improve over time, or gradually worsen.
As for the prevalence of leukoencephalopathy, due to the various types it covers, it is not yet established. Depending on the type of condition we treat, it may be more or less frequent. Although in general, these diseases are not widespread.
Causes of Leukoencephalopathy
Since leukoencephalopathy is any condition in which part of the white matter, whether acquired or inherited, is affected, the causes are very numerous.
In addition, there are different types of encephalopathies according to their causes and the characteristics of the damages. So that each causal factor generates a type of damage in the different white matter, which, as a consequence, produces different symptoms.
The conditions that can cause a leukoencephalopathy are very diverse:
- Genetic heritage: There are a series of genetic mutations that can be inherited from parents to children and that facilitate the appearance of leukoencephalopathy. Autosomal dominant cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) would be an example, as it is caused by the involvement of the Notch3 gene.
There are authors who call leukodystrophies the degeneration of white matter due to genetic factors. However, sometimes the distinction between what conditions have genetic causes and those with acquired causes is not absolutely clear. In fact, there are conditions in which a disease can arise from both types of causes.
- Virus: It has been found that leukoencephalopathy can develop if the body is not able to fight a certain virus, due to an abnormality or weakness of the immune system.
This is what happens in progressive multifocal leukoencephalopathy, which appears due to the presence of the JC virus. There are also cases in which the measles virus appears to be the cause of white matter deterioration, as is the case with Van Bogaert sclerosing leukoencephalopathy.
- Vascular problems: Some Stroke , the hypertension wave Encephalopathy ischemic hypoxia (Lack of oxygen or blood flow in the brain of the newborn), can affect the integrity of the white matter of the brain.
- Poisoning, drug or drug abuse
- Treatments for Chemotherapy Such as radiation therapy, can cause progressively increasing lesions in the white matter. These are: cisplatin, 5-fluorouracil, 5-florauracil, levamisole and Ara-C.
There are authors who divide the causes of leukoencephalopathy into 5 groups: non-infectious inflammatory, infectious inflammatory, toxic-metabolic, hypoxic ischemic and traumatic (Van der Knaap & Valk, 2005).
However, sometimes certain diseases do not fit into particular categories, as they can have several different causes at the same time.
General Symptoms
- In children, a characteristic pattern of the development of skills and abilities. It consists of a period of normal development followed by stagnation in the acquisition of skills, and finally a decrease or regression. Another sign is that this occurs after injuries, infections, or any brain damage.
- Seizures or epileptic seizures
- Spasticity Progressive, or increasingly stiff and tense muscles.
- ataxia Or difficulties in coordinating movements that have a neurological origin.
- Poor balance that cause problems walking.
- Cognitive deficits or cognitive slowness in care processes, the memory , And learning.
- Visual difficulties. They often affect the cornea, retina, lens, or optic nerve.
- In some children with leukoencephalopathy, the circumference of the skull is greater than normal, something called Macrocephaly .
- Successive episodes of stroke or stroke.
- Irritability.
Types
There are many diseases that can be included under the term leukoencephalopathy. Some of them are:
- Autosomal dominant cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) or Cerebral microangiopathy.
It is an inherited disease that causes multiple cerebral infarctions in the minor arteries, affecting part of the white matter of the brain. The first symptoms appear about 20 years of age and consist of migraines, psychiatric disorders and frequent cerebrovascular accidents.
- Leukoencephalopathy with white evanescent substance
It is also called childhood ataxia with central nervous system hypomelination (CACH).
It is an autosomal recessive hereditary condition. This means that it appears when both parents transmit the same genetic mutation to their child. The mutation can be found in any of these 5 genes: EIF2B1, EIF2B2, EIF2B3, EIF2B4, or EIF2B5.
It is usually diagnosed in infancy between 2 and 6 years of age, although there have been cases of onset in adulthood.
The symptoms are Cerebellar ataxia (Loss of muscle control due to deterioration of the cerebellum), spasticity (abnormal muscle tension), epilepsy , Vomiting, coma, movement problems and even fever.
- Progressive multifocal leukoencephalopathy
It appears in people with important deficiencies in their immune system, since this one is not able to brake the JC virus . Its activity causes a large number of progressive progressive lesions that produce cerebral demyelination.
As the name implies, symptoms progressively arise, consisting of Cognitive impairment , Visual loss due to occipital lobe ( Part of the brain Which participates in the vision) and Hemiparesis . It is also routinely associated with Optic neuritis.
- Leukoencephalopathy with axonal spheroids
It is a hereditary condition that comes from mutations in the CSF1R gene. The symptoms associated with it are tremors, convulsions, stiffness, ataxia of gait, progressive deterioration of memory and executive functions, and depression .
- Sclerosing leukoencephalopathy of Van Bogaert
This is the demyelination of the cerebral cortex that appears a few years after the measles virus. The symptoms consist of a slow and progressive neurological deterioration that causes eye problems, spasticity, changes in personality, sensitivity to light and ataxia.
In this case, the loss of white matter is due to the ingestion, inhalation or intravenous injection of certain drugs or drugs, as well as exposure to environmental toxins or treatment of chemotherapy .
It may also appear from carbon monoxide poisoning, ethanol poisoning, methanol, ethylene, or ecstasy ingestion.
The symptoms depend on each toxicant, amount received, exposure time, medical history and genetics. Usually they are usually difficulties in attention and memory, problems of balance, dementia and even death.
In many of these cases, the effects can be reversed when the toxicant causing the problem is eliminated.
- Mega-encephalic leukoencephalopathy with subcortical cysts
It is an autosomal recessive genetic condition produced by mutations in the MLC1 and HEPACAM genes. It stands out for macrocephaly (skull overdeveloped) at a young age, mental deterioration and progressive motor, epileptic seizures and ataxia.
- Hypertensive leukoencephalopathy
It is the degeneration of the white matter by a sudden increase in blood pressure. It causes an acute confusional state, in addition to headaches, convulsions and vomiting. Haemorrhages occur frequently in the retina of the eye.
It can be treated effectively with antihypertensive drugs.
- Reversible posterior leukoencephalopathy syndrome (SLPR)
The symptoms associated with this syndrome are loss of vision, seizures, headaches and confusion.
A wide variety of causes can occur, such as malignant hypertension (a very rapid and sudden rise in blood pressure, systemic lupus erythematosus, eclampsia (Seizures or coma in the pregnant woman associated with hypertension), or certain medical treatments that suppress the activity of the immune system (such as immunosuppressive drugs, such as cyclosporine).
In a brain scanner, edema can be observed, that is, unusual fluid accumulation in the tissues.
Symptoms tend to disappear after a while, although vision problems can be permanent.
Diagnosis of leukoencephalopathy
If there are symptoms such as seizures, motor difficulties or lack of coordination of movements, it is likely that the health professional decides to perform a brain scanner.
One of the best techniques of neuroimaging is the magnetic resonance , From which images of the brain of high quality can be obtained thanks to the exposure to magnetic fields.
If these images show certain patterns of damage localized in the white matter of the brain, the specialist may conclude that there is a leukoencephalopathy.
It is advisable to perform an ophthalmological examination, since, as they say, the eyes are a window to our brain. It is important to remember that abnormalities or ophthalmological changes are very frequent in leukoencephalopathy.
It is also necessary a neurological examination to detect the existence of spasticity or excessive muscular tension, being able to also occur hypotonía (the opposite).
Under certain conditions, such as progressive multifocal leukoencephalopathy, an analysis of the cerebrospinal fluid may be performed. The technique is called PCR (Polymerase Chain Reaction), and is performed to detect the JC virus; Which is the cause of this disease.
Treatment
Treatment will focus on the underlying causes that have caused damage to the white matter. As the causes are very diverse, the different treatments are also different.
Thus, if the factors that have caused the disease have vascular origins or are related to the hypertension , Keeping this in check could be of great help.
For leukoencephalopathies whose cause is immunodeficiency, treatment will be focused on reversing that condition, such as the use of drugs Antiretrovirals In HIV.
If, on the contrary, it is due to exposure to toxins, drugs or drugs; The best way to recover is to stop contact with those substances.
It is also recommended to complement the treatment of the causes of leukoencephalopathy with other symptomatic ones that serve to alleviate the existing damages. That is, neuropsychological rehabilitation to work cognitive impairment, psychological assistance to help the patient deal with their situation emotionally, physical training to improve muscle tone, etc.
If leukoencephalopathy appears due to inherited genetic mutations, the treatments will be focused on preventing the progression of the disease, improving the person's quality of life and other preventive methods.
One form of prevention may be a genetic test if other relatives have suffered any of these conditions. To check if you are carrying any genetic abnormality related to leukoencephalopathy that can be transmitted to future children.
References
- Abarca Barriga, Hugo Hernán, Castro Mujica, María del Carmen, & Gallardo Jugo, Bertha Elena. (2013). Megalencephalic leukoencephalopathy with subcortical cysts (Van der Knaap disease). Revista Cubana de Pediatría, 85 (1), 106-111.
- Deborah, L. &. (2012). Clinical Approach to Leukoencephalopathies. Seminars in Neurology, 32 (1): 29-33.
- Differential diagnosis of MS (II). (13 June 2013). Obtained from Empapers.
- Filley, C.M. (s.f.). Leukoencephalopathy, Disconnection, and Cognitive Neuroscience. Retrieved on October 26, 2016, from Touchneurology.
- Hypertensive leukoencephalopathy. (S.f.). Retrieved on October 26, 2016, from Wikipedia.
- Leukoencephalopathy. (S.f.). Retrieved on October 26, 2016, from Wikipedia.
- Marjo S. van der Knaap and Jaap Valk, eds. (2005). Magnetic Resonance of Myelination and Myelin Disorders, 3rd ed. New York: Springer.
- Survivor Issues: Leukoencephalopathy. (April 17, 2011). Retrieved from the Ped-Onc Resource Center.