What is Leukodystrophy used for?

In general, leukodystrophy is not considered curable. Its course is very different and can occur in newborns as well as in babies, small children and school children, but also in adults. Hope lies in research and in the first experimental treatments with a lentiviral vector.

What is leukodystrophy?

In some cases, long-term freedom from symptoms can be achieved by transplantation of stem cells (HCST) or bone marrow (BMT) in the pre-symptomatic stage. See AbbreviationFinder for abbreviations related to Leukodystrophy.

The term leukodystrophy is composed of the Greek words “leukos” (white) and “dys” (bad) as well as “trophe” (nutrition). This disease, which can manifest itself in different forms, destroys the central nervous system in the brain and spinal cord. Children as well as adults can be affected.

The myelin, the white substance that surrounds the nerves, is attacked. The result is that the information flow of the nerve currents can no longer be properly transmitted by the myelin. Either it is not possible to establish the required connection or the connection is defective in its function. Leukodystrophy is divided into five groups:

Peroxisomate diseases:

  • Adrenoleukodystrophy/Adrenomyeloneuropathy
  • In adults Refsun’s disease
  • Zellweger diseases with Zellweger syndrome and neonatal leukodystrophy

Lysomatous diseases:

  • Metachromatic leukodystrophy and Krabbe’s disease

Leukodystrophies with hypomyelination:

  • Pelizaeus-Merzbacher disease
  • a disease resembling Pelizaeus
  • spastic paraphlegia 2
  • Leukodystrophies with polymerase III
  • atypical leukodystrophies

Orthochromatic leukodystrophies:

  • Alexander’s disease
  • Canavan’s disease
  • CACH/VWM syndrome
  • Cystic Leukoencephalopathy with Megalencephaly|Cystic Leukoencephalopathy with Megalencephaly (MLC)

Unknown diseases:

  • Orthochromatic leukodystrophy in pigmented form
  • Leukodystrophy associated with progressive ataxia, hearing loss and cardiomyopathy

Causes

Berlin researchers from the Leibnitz Institute for Molecular Pharmacology (FMP) have discovered that a fine and sensitive interaction between three proteins in the white matter of the brain is disturbed. This shows that a neurological disease does not automatically have to be based on a defect in the actual nerve cells.

The importance of the network of glial cells in which the nerve tracts are embedded has been underestimated. Rather, there is degeneration of the white matter of the brain, particularly the myelin sheaths that wrap around the nerve fibers. This network is closely connected to the blood vessels in the brain and nourishes the nerve cells. Mutations in the genome are said to be responsible for errors in this structure.

Symptoms, Ailments & Signs

The symptoms of leukodystrophy are very different. Very often those affected can only walk or coordinate their own movements with great effort. Spastic paralysis or epileptic seizures can occur as additional symptoms.

A common symptom in children is that they learn to walk very late, are not as mobile and nimble as other children of the same age, and their gait is staggered and/or legs apart. Over time, the gait usually becomes more and more sluggish. Learning at school becomes more and more difficult due to an increasing lack of concentration and later memory loss. Of course, there are also cases with mild symptoms.

Often the first signs can already be diagnosed in infancy or toddler age, in other cases this is only possible in adulthood. There are even cases in which the severity of the course of the disease is reduced. Despite this, leukodystrophy remains incurable to this day.

Diagnosis & course of disease

Course of the disease in the four forms of leukodystrophy:

  • In the congenital form, which can be identified at birth, the babies die within the first few hours or days.
  • In the infantile form, children can reach an age of around two to six years. Arms and legs are characterized by increasing weakness and clumsiness known as ataxia. The articulation also becomes increasingly indistinct (dysarthria). The further course is characterized by swallowing and breathing disorders as well as muscle cramps (spasms), which are very painful. The ability to see and hear is also steadily declining. Epileptic seizures are not uncommon.
  • The juvenile form of leukodystrophy occurs somewhat later and is not as dramatic. Difficulties in school and a nonspecific clumsiness with walking are symptomatic.
  • In the very rare adult form of the disease, psychological changes and poor performance initially lead to job loss. Sometimes there is also alcoholism. After years, an intellectual decline can be observed. Movement disorders associated with dystonia, spasticity and ataxia can form the next stage in the course of leukodystrophy. It is not uncommon for dysarthria and loss of vision to occur.

A detailed record of the previous course and a family history are at the beginning. A thorough physical examination follows. An MRI is done to detect changes in the white matter of the brain. In addition, abdominal sonography, electrophysiological nerve examinations and laboratory and/or biochemical examinations are often carried out. Also neuropsychological tests.

Complications

Unfortunately, in most cases, leukodystrophy cannot be cured. It occurs mainly in children and schoolchildren and can lead to significant limitations in everyday life and in the development of those affected. In most cases, those affected suffer from paralysis and other sensory disorders. Epileptic seizures are also not uncommon and can significantly restrict the affected person’s everyday life.

It is not uncommon for patients to depend on the help of other people in their everyday lives and are no longer able to carry out many things. Loss of memory and a lack of concentration are also not uncommon. Furthermore, children can be affected by bullying or teasing. Above all, learning and understanding content is often very difficult for those affected and can lead to limitations in adulthood.

A causal treatment of leukodystrophy is unfortunately not possible. Therefore, treatment is only symptomatic and aims to limit the symptoms. There are no further complications. However, patients are dependent on lifelong therapy. Parents and relatives often suffer from psychological problems and need appropriate treatment.

When should you go to the doctor?

Spastic paralysis, epileptic seizures and other serious symptoms must be examined by a doctor immediately. Parents of affected people should call an ambulance when these symptoms first appear. Leukodystrophy is not necessarily the cause, but it is usually a serious condition that needs to be diagnosed and treated. Other red flags to look into are learning difficulties, poor concentration, and worsening memory loss. The disease can often be diagnosed in infancy.

Therefore, a specialist should be consulted at an early stage if there is a first suspicion. Parents who notice unusual symptoms in their child that do not go away on their own should also call a medical professional. Leukodystrophy is probably a hereditary disease, which is why a specialist clinic for hereditary diseases should be consulted. Other points of contact are the general practitioner or an internist. In addition, a neurologist must be called in, who can create an individual therapy in cooperation with physiotherapists and therapists. The therapy takes place under close medical supervision.

Treatment & Therapy

With regard to metachromatic leukodystrophy, the therapeutic options are very limited. The focus is on palliative measures to relieve pain and muscle spasms. Antiepileptic drugs are prescribed to reduce the severity of the seizures. In addition, there is a special diet or tube feeding.

In some cases, long-term freedom from symptoms can be achieved by transplantation of stem cells (HCST) or bone marrow (BMT) in the pre-symptomatic stage. These two treatment methods are used for metachromatic leukodystrophy, adrenoleukodystrophy and Krabbe disease. It should be noted that there is a high risk of mortality.

In order to clarify the pathogenesis and to develop new forms of therapy, scientific trials are pending. A further development of enzyme replacement therapy (ERT) is envisaged as a result. It is used therapeutically for Gaucher or Fabry disease, mucopolysaccharidosis types I, II and IV, and Pompe disease.

Another part of the therapy is symptomatic therapy with physiotherapy, ergotherapy and logotherapy. In addition, there is a medicinal setting with regard to spasms, dystonia or epilepsy and other symptoms.

Special forms of leukodystrophy are treated with substrate reduction or enzyme replacement therapy. With Lorenzo`s oil a progression of the X-chromosomal adrenoleukodystrophies should be achieved. The therapy also includes the avoidance of secondary diseases.

The stimulation of the nerve cells is another therapeutic approach. Comprehensive stimulus mediation as well as input and training are part of it. With as much sport as possible, the course of the disease can often be positively influenced.

Outlook & Forecast

The prognosis of leukodystrophy is considered unfavorable. Despite medical developments and health advances, the disease is classified as incurable to date. It is a genetic disorder that cannot be treated for legal reasons. Physicians and researchers are not yet allowed to change human genetics. For this reason, the focus of medical care is on improving well-being and treating symptoms.

Due to leukodystrophy, there are disturbances in the movement sequences, limitations in memory and the possibility of seizures. In some patients, the symptoms are very mild. They can be well controlled by administering medication and regularly monitoring health developments. The quality of life is improved overall in the care, since an appropriate treatment measure is taken immediately after the perception of irregularities.

In the case of severe disease progression, the prognosis worsens significantly. In addition to the physical irregularities, the impairments can also lead to mental stress. Consequential disturbances are possible and the immediate environment is also exposed to developments that have to be dealt with in everyday life. In acute situations, intensive medical care is necessary. These are mostly temporary in nature and are intended to ensure the survival of those affected.

Prevention

Preventive measures are not yet known because it is a hereditary disease. Therefore, it is important to recognize the disease as early as possible and start treatment.

Aftercare

As a rule, the options for aftercare in the case of leukodystrophy are relatively severely limited. The person affected with this disorder is dependent on permanent treatment in order to alleviate the symptoms and to avoid further complications. Early diagnosis and treatment have a very positive effect on the further course of the disease.

The patient must ensure that the medication is taken regularly, and possible interactions with other medications should also be taken into account. In children, parents must monitor this so that there are no disturbances or complications.

Furthermore, most patients are dependent on physiotherapy to alleviate the discomfort in the muscles. Many of the exercises from this therapy can also be carried out at home in order to increase the mobility of the person concerned. The life expectancy of the patient is not negatively affected by this disease.

Since leukodystrophy can also lead to psychological problems or depression in some cases, the loving care of friends and family is very soothing.

You can do that yourself

The possibilities for self-help are very limited in leukodystrophy. The disease is considered incurable. Nevertheless, various measures can be taken to improve well-being, which can be carried out independently by the patient and their relatives.

A special diet is useful to limit intake of long chain fatty acids. The consumption of foods with a high proportion of fatty acids should be avoided. The dietary change is not aimed at a low-fat diet. However, the content of saturated long-chain fatty acids should be reduced. The intake of peanuts, milk products, meat products or cakes should be avoided. Fats or oils with a low fat content are health-promoting. High-quality vegetable oils cover the necessary requirements sufficiently. Long-term studies have shown that adherence to the diet leads to an improved course of the disease.

In addition to food intake, the patient can turn to various self-help groups. There are nationwide initiatives for those affected by leukodystrophy. In addition to voluntary associations, there are several forums in which patients and their families can exchange ideas. Cognitive techniques can be used to minimize concentration and memory problems. Targeted training or leisure activities help to optimize performance. To prevent motor impairments, regular exercises should also be carried out in this area.

Leukodystrophy