Leukodystrophy

Generally applies Leukodystrophy as incurable. Their course is very different and can occur in newborns as well as in babies, small and school children, but also adults. Hope lies in research and in the first experimental treatments with a lentiviral vector.

What is Leukodystrophy?

The term Leukodystrophy is made up of the Greek word "leukos" (white) and "dys" (bad) as well as "trophe" (nutrition). This disease, which can occur in different forms, destroys the central nervous system in the brain and spinal cord. Children as well as adults can be affected.

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

Peroxisomate diseases:

• Adrenoleukodystrophy / adrenomyeloneuropathy

• Refsun's disease in adults

• Zellweger diseases with Zellweger syndrome and neonatal leukodystrophy

Lysomate 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 disease

• Canavan's disease

• CACH / VWM syndrome

• Cystic Leukoencephalopathy with Megalencephaly Cystic Leukoencephalopathy with Megalencephaly (MLC)

Unknown diseases:

• Orthochromatic leukodystrophy in pigmented form

• The leukodystrophy is accompanied by progressive ataxia, hearing loss and cardiomyopathy

causes

Berlin researchers from the Leibnitz Institute for Molecular Pharmacology (FMP) have discovered that the fine and sensitive interaction of 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 pathways are embedded has been underestimated. Rather, there is degeneration of the white matter in the brain, in particular the myelin sheaths that wrap around the nerve fibers. This network is closely connected to the blood vessels in the brain and feeds the nerve cells. Mutations in the genetic material are said to be responsible for errors in this structure.

Symptoms, ailments & signs

The symptoms of leukodystrophy vary widely. Very often those affected can only walk with great effort or coordinate their own movement sequences. Spastic paralysis or epileptic seizures can appear 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 lanky and / or legs apart. Over time, the gait usually becomes more and more sluggish. Learning at school is becoming more and more difficult due to an increasing lack of concentration and a later loss of memory. Of course, there are also cases with mild symptoms.

Often the first signs can already be diagnosed in babies or toddlers, in other cases this is only possible in adulthood. There are even cases when the severity of the course of the disease is reduced. Nevertheless, leukodystrophy remains incurable to this day.

Diagnosis & course of disease

The four types of leukodystrophy:

• In the congenital form, which is already recognizable at birth, the babies die within the first 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. Eyesight and hearing are also steadily declining. Epileptic seizures are not uncommon.

• The juvenile form of leukodystrophy occurs a little later and is not as dramatic. Difficulties at school and an unspecific walking awkwardness are symptomatic.

• In the very rare adult form, there is initially a loss of job due to psychological changes and poor performance. Sometimes there is also alcoholism. An intellectual decline can be observed after years. 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 recording of the previous course and a family history are at the beginning. A full physical examination follows. An MRI is done to check for changes in white matter in the brain. Abdominal sonography, electrophysiological nerve examinations and laboratory and / or biochemical examinations are also often carried out. Also neuropsychological tests.

Complications

Unfortunately, in most cases, leukodystrophy cannot be cured. It occurs primarily in children and schoolchildren and can lead to significant restrictions in everyday life and in the development of those affected. In most cases, those affected suffer from paralysis and other disorders of sensitivity. Epileptic seizures also occur not infrequently and can significantly limit the everyday life of the person affected.

It is not uncommon for patients to rely on the help of other people in their everyday life and can no longer do many things. Loss of memory and poor concentration are not uncommon. Furthermore, children can be affected by bullying or teasing. In particular, 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, the treatment is only symptomatic and aims to reduce the symptoms. There are no further complications. However, the 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 clarified immediately by a doctor. Parents of affected individuals should call an ambulance when these symptoms first arise. The underlying disease may not necessarily be leukodystrophy, but it is usually a serious disease that needs to be diagnosed and treated. Other warning signs that should be investigated are learning difficulties, poor concentration, and increasing memory loss. The disease can often be diagnosed as early as infancy.

A specialist should therefore be consulted at an early stage if there is any initial suspicion. Parents who notice unusual symptoms in their child that do not go away on their own should also call a health professional. Leukodystrophy is probably a hereditary disease, which is why a specialist clinic for hereditary diseases should be visited. Other contact points are the family doctor or an internist. In addition, a neurologist must be involved, 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. In order to reduce the severity of the seizures, antiepileptic drugs are prescribed. There is also a special diet or tube feeding.

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

Scientific trials are pending to clarify the pathogenesis and develop new forms of therapy. A further development of enzyme replacement therapy (ERT) is planned as a result. In terms of therapy, it is used in Gaucher or Fabry disease, mucopolysaccharidosis types I, II and IV and Pompe disease.

Another therapy component is symptomatic therapy with physio, occupational therapy and logotherapy. In addition, there is a medicinal attitude towards 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-linked adrenoleukodystrophies should be achieved. The therapy also includes avoiding secondary diseases.

The stimulation of the nerve cells is another therapeutic approach. Comprehensive stimulus transmission 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. The disease is classified as incurable to date, despite medical developments and health progress. It is a genetic disorder that cannot be treated for legal reasons. So far, doctors and researchers have not been allowed to change human genetics. For this reason, the focus of medical care is on improving well-being and treating symptoms.

Due to leukodystrophy, movement disorders, memory impairment and the possibility of seizures occur. In some patients the symptoms are very minor. They can be well controlled through the administration of medication and regular monitoring of 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.

The prognosis worsens significantly if the disease progresses significantly. In addition to the physical irregularities, the impairments can also lead to psychological stress. Consequential disorders are possible and the immediate environment is also exposed to developments that have to be dealt with in everyday life. Intensive medical care is necessary in acute situations. These are mostly of a temporary nature and are intended to ensure the survival of the person affected.

prevention

So far, no preventive measures are known as it is a hereditary disease. It is therefore important to identify the disease as early as possible and initiate treatment.

Aftercare

As a rule, the options for follow-up care for leukodystrophy are relatively limited. With this disorder, the affected person is dependent on permanent treatment to alleviate the symptoms and avoid further complications. An 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 the case of children, parents must monitor this so that there are no disturbances or complications.

Most patients also need physical therapy to relieve the discomfort in the muscles. Many of the exercises from this therapy can also be performed in your own 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 in some cases lead to psychological complaints or depression, the loving care of friends and family is very soothing.

You can do that yourself

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

A special diet is useful to limit the intake of long chain fatty acids. Consumption of foods high in fatty acids should be avoided. The change in food is not geared towards a low-fat diet. However, the content of saturated long-chain fatty acids should be reduced. Do not use peanuts, dairy products, meat products or cakes. Fats or oils with a low fat content are beneficial to health. High-quality vegetable oils sufficiently cover the necessary requirements. Long-term studies have shown that adherence to the diet leads to improved disease progression.

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 sick people and relatives can exchange ideas. Cognitive techniques can be used to minimize concentration and memory problems. Targeted training or leisure activities help to optimize performance. Regular exercises should also be carried out in this area to prevent motor impairments.