In general, leukodystrophy is not considered curable. Its course varies widely and can occur in newborns as well as in babies, young children, schoolchildren, and adults. Hope lies in research and initial experimental treatments with a lentiviral vector.
What is leukodystrophy?
The term leukodystrophy is made up of the Greek words “leukos” (white) and “dys” (bad) and “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. The myelin, the white substance surrounding the nerves, is attacked. As a result, the myelin can no longer properly transmit the information flow of the nerve currents. Either it is not possible to establish the necessary connection or the connection is damaged in its function. Leukodystrophy is divided into five groups:
Peroxisomate diseases:
- Adrenoleukodystrophy/adrenomyeloneuropathy.
- In adult Refsun’s disease
- 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’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 subtle and sensitive interaction of three proteins is disturbed in the white matter of the brain. This shows that a neurological disease does not automatically have to be due to 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 a degeneration of the white matter of the brain, particularly the myelin sheaths that wrap the nerve fibers. This network is closely connected to the blood vessels in the brain and nourishes the nerve cells. Mutations in the genetic material are thought to be responsible for defects in this structure.
Symptoms, complaints, and signs
The symptomatology of leukodystrophy manifests itself very differently. Very often, affected individuals can only walk or coordinate their own movements with great effort. Spastic paralysis or epileptic seizures can occur as further 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 spindly and/or wide-legged. 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 a later loss of memory. Of course, there are also cases with mild symptoms. Often, the first signs can already be diagnosed in baby or toddler age, in other cases this is only possible in adulthood. There are even cases in which the severity of the disease course is reduced. Nevertheless, leukodystrophy remains incurable to this day.
Diagnosis and course of the disease
Disease course of the four forms a leukodystrophy:
- In the congenital form of progression, which is evident at birth, babies die within the first few hours or days.
- In the infantile form of progression, children can reach an age of circa two to six years. Arms and legs are characterized by increasing weakness and clumsiness, ataxia. Articulation also becomes increasingly slurred (dysarthria).The further course is characterized by swallowing and breathing disorders as well as muscle cramps (spasms), which are very painful. Vision and hearing also steadily decrease. Not infrequently, epileptic seizures are added.
- The juvenile course of leukodystrophy occurs somewhat later and is not as dramatic. School difficulties and a nonspecific clumsiness in walking are symptomatic.
- In the very rare adult progressive form, job loss occurs initially due to psychological changes and poor performance. This is sometimes accompanied by alcoholism. After years, intellectual decline is noted. Movement disorders associated with dystonia, spasticity and ataxia can form the next stage in the course of leukodystrophy. Not infrequently, there is also dysarthria and loss of vision.
A detailed record of the previous course and a family history are at the beginning. This is followed by a comprehensive physical examination. To detect changes in the white matter of the brain, an MRI is performed. Furthermore, abdominal sonography, electrophysiologic nerve testing, and laboratory and/or biochemical testing are often performed. So are neuropsychological tests.
Complications
In most cases, unfortunately, leukodystrophy cannot be cured. It occurs mainly in children and schoolchildren, and in the process 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 daily life of the affected person. It is not uncommon for patients to be dependent on the help of other people in their daily lives and to be unable to do many things. Memory loss 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 not infrequently very difficult for those affected and can lead to limitations in adulthood. Unfortunately, a causal treatment of leukodystrophy is not possible. Therefore, treatment is only symptomatic and aims at limiting the symptoms. This does not lead to further complications. However, patients are dependent on lifelong therapy. In this process, parents and relatives not infrequently also suffer from psychological discomfort and require appropriate treatment.
When should one go to the doctor?
Spastic paralysis, epileptic seizures, and other severe symptoms require immediate medical attention. Parents of affected individuals should call an emergency physician when these symptoms first appear. While not necessarily underlying leukodystrophy, there is usually a serious condition that needs to be diagnosed and treated. Other alarm signs that should be investigated include learning difficulties, poor concentration and worsening memory loss. The disease can often be diagnosed as early as infancy. That is why a specialist should be consulted at an early stage if the first suspicions are raised. Parents who notice unusual symptoms in their child that do not subside on their own are also best advised to call in 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 family doctor or an internist. In addition, a neurologist must be consulted who, in cooperation with physiotherapists and therapists, can create an individual therapy. Therapy takes place under close medical supervision.
Treatment and therapy
Regarding metachromatic leukodystrophy, treatment 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. This is supplemented by a special diet or tube feeding. Stem cell transplantation (HCST) or bone marrow transplantation (BMT) in the presymptomatic stage can in some cases achieve long-term freedom from symptoms. These two treatment methods are used in metachromatic leukodystrophy, adrenoleukodystrophy and Krabbe disease. It must be taken into account that there is a high mortality risk.Scientific trials are pending to clarify the pathogenesis and to open up new forms of therapy. A further development of enzyme replacement therapy (ERT) is envisaged as a result. In terms of therapy, it is used for Gaucher or Fabry disease, mucopolysaccharidosis types I, II and IV, and Pompe disease. Another therapy component is symptomatic therapy with physio, ergotherapy and logotherapy. In addition, a medicamentous adjustment concerning the spasms, a dystonia or epilepsy and other symptoms is necessary. Special forms of leukodystrophy are treated with substrate reduction or enzyme replacement therapy. Lorenzo`s oil is used to achieve progression of X-linked adrenoleukodystrophies. The therapy also includes the prevention of secondary diseases. Stimulation of nerve cells is another therapeutic approach. Comprehensive stimulus delivery as well as input and training are part of this. With as much exercise as possible, the course of the disease can often be positively influenced.
Outlook and prognosis
The prognosis of leukodystrophy is considered unfavorable. The disease is classified as incurable to date, despite medical developments and advances in health. It is a genetic disorder that cannot be treated for legal reasons. Doctors and researchers are not yet allowed to alter 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 movement, limitations in memory, and the possibility of seizures. In some patients, the symptoms are very mild. They can be well controlled by the administration of medication and regular monitoring of health developments. The overall quality of life is improved in care, as appropriate treatment action is taken immediately after the perception of irregularities. In cases of severe disease progression, the prognosis deteriorates significantly. In addition to the physical irregularities, psychological stress can also occur due to the impairments. Consequential disorders are possible and the close environment also faces developments that have to be managed in everyday life. In acute situations, intensive medical care is necessary. These are usually of a temporary nature and are intended to ensure the survival of the affected person.
Prevention
Preventive measures are not yet known, since it is a hereditary disease. Therefore, it is important to detect the disease as early as possible and initiate treatment.
Follow-up
As a rule, the options for follow-up care in leukodystrophy are relatively limited. Affected individuals rely on ongoing treatment for this disorder to relieve symptoms and prevent 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 the case of children, the parents must monitor this so that there are no disturbances or complications. Furthermore, most patients rely on physical therapy to relieve discomfort in the muscles. Many of the exercises from this therapy can also be performed in the patient’s own home to increase mobility. The patient’s life expectancy is not negatively affected by this condition. Since leukodystrophy can also cause psychological discomfort or depression in some cases, the loving care of friends and family is very soothing.
Here’s what you can do yourself
The options 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 performed independently by the patient and his or her relatives. 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 of food is not aimed at a low-fat diet. However, the content of saturated long-chain fatty acids should be reduced.The intake of peanuts, dairy products, meat products or cakes should be avoided. Fats or oils with a low fat content are beneficial to health. High-quality vegetable oils sufficiently cover the necessary requirement. Long-term studies have shown that adherence to the diet leads to an improved course of the disease. In addition to dietary intake, the patient can turn to various support groups. There are nationwide initiatives for those affected by leukodystrophy. In addition to voluntary associations, there are several forums in which an exchange between sufferers and relatives is made possible. 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 performed in this area to prevent motor impairments.
