Alexander’s disease is a very rare, fatal disease that destroys the white matter in the brain and spinal cord. It is also known as Alexander syndrome, Alexander disease, and dysmyelinogenic leukodystrophy.
What is Alexander’s disease?
Pathologist William Stewart Alexander was the first to describe Alexander’s disease as a disease. It is one of the leukodystrophy diseases. These are genetic metabolic diseases in which the white matter of the nervous system degenerates. In Alexander syndrome, the white matter in the brain and spinal cord is affected. See nonprofitdictionary for Minimal Change Glomerulonephritis (abbreviated as MCGN).
Alexander’s disease differs from other leukodystrophic diseases by the infestation of special tissue cells in the nervous system, the astrocytes, with Rosenthal fibers. The Rosenthal fibers are worm-shaped inclusions in the cell. The disease is divided into four forms, which depend on the age of those affected. The infantile form is the most common. It occurs in young children. There is also the neonatal form in newborns, the juvenile form in adolescents and the adult form in adults.
Sometimes scientists only use the term Alexander’s disease for the infantile form. Boys suffer from the infantile form more often than girls. The rarity of this disease is shown by the fact that doctors estimate the number of scientifically examined sufferers worldwide to be around 150 people. In Germany there were only 50 proven cases in 2011.
Causes
The disease is due to a genetic mutation. The gene that produces the protein GFAP is affected by this mutation. It usually occurs spontaneously, which means that children of healthy parents are also susceptible to this disease. Research has shown that the mutation seems to come mostly from the father’s genes. It has not yet been clarified how this change in the gene leads to the degeneration of the nerve cells and the typical changes in the brain.
Symptoms, Ailments & Signs
The disease manifests itself differently depending on age. In the infantile form, there are clear developmental disorders in motor and sensory functions. There are also disturbances in the coordination of movements. In addition to enlargement of the skull, another symptom is enlargement of the brain. Those affected have difficulty swallowing and suffer from spasticity, ie the contraction of individual muscles or muscle groups and seizures.
In the neonatal form, the same symptoms appear and worsen over a much shorter period of time. The symptoms of the juvenile form are case-dependent. Not all signs of the disease appear. Sometimes adolescent patients do not have seizures and do not suffer from spasticity. The enlargement of the skull known as macrocephalus also occurs less frequently in the juvenile form.
The typical symptoms of Alexander’s disease occur much less frequently and in a milder form in the adult form. However, doctors have found that in adults the brainstem is more affected by the destruction. Speech disorders and involuntary twitching of the uvula occur.
Diagnosis & course of disease
Alexander’s disease is a fatal disease. It leads to severe disabilities and ends in cardiovascular failure. After the disease was discovered, it was initially customary to make a diagnosis through a biopsy, the removal of a tissue sample. In the meantime, a magnetic resonance imaging of the brain is carried out to check the diagnosis of a juvenile form.
In order to see the diagnosis as certain, doctors use four criteria when evaluating the brain scan:
- The first criterion is a change in the central white matter in the brain.
- Another confirmation is the presence of a periventricular seam. Depending on the type of scan, darker or lighter zones appear in certain areas of the brain, which do not have this color gradation during normal development.
- The enrichment of certain brain regions with contrast medium is also an indication of the disease.
- The fourth criterion is anatomical abnormalities in the area of the thalamus, the brainstem and the basal ganglia, which are located below the cerebral cortex. In adults, recognizable tissue atrophy and signal changes in the brainstem and spinal cord are additional clues.
Complications
Alexander’s disease causes the patient to experience very serious symptoms and complications in everyday life. As a rule, various motor disorders appear, so the deforestation of the child is significantly limited. The coordination and movement of the patient is also restricted by Morbus Alexander, so that the patients are dependent on the help of other people in their everyday life.
There are also problems with swallowing and the development of spasticity. The swallowing difficulties can also lead to difficulty in taking food or liquids. It is not uncommon for the parents of those affected to be severely affected by Alexander’s disease and suffer from psychological problems or depression. As the disease progresses, speech disorders occur, which can also lead to bullying or teasing in children.
The patient’s quality of life is significantly reduced by Alexander’s disease. The life expectancy of those affected is also reduced by the disease, so that the affected person ultimately dies due to heart failure. Treating the disease can only reduce the symptoms, but not eliminate them completely. Furthermore, the relatives or the parents often need psychological treatment in order to cope with the psychological stress.
When should you go to the doctor?
If developmental disorders are noticed in various areas in a growing child, a doctor should always be consulted. In the case of physical as well as mental abnormalities, it is advisable to carry out a medical examination so that the symptoms can be clarified. Disturbances and irregularities in the movement sequences, the motor function as a whole and the sensorimotor function must be examined and treated.
If there are behavioral problems and inconsistencies in locomotion in direct comparison to children of the same age, medical help is required. Since Alexander’s disease has a fatal course, a doctor’s visit should be made at the first signs and the suspicion of a possible health problem.
With an individual treatment and therapy plan, existing symptoms can be treated medically and the quality of life of the patient can be significantly improved. In the case of speech disorders, cramps, a seizure disorder or spasticity, a doctor’s visit is necessary. If there are abnormalities in the muscular system, contractions of individual muscle fibers or an enlarged head shape, a doctor should be consulted.
An optical peculiarity of the skeletal system is often a sign of a health disorder. It should be discussed with a doctor immediately. Disorders of voluntary movement are further indications of an existing disease. In particular, an irregularity of the uvula indicates Morbus Alexander and should be presented to a doctor.
Treatment & Therapy
The different shapes vary in length and weight. Infants with the disease die within a few months. Adults, children and adolescents can live with this disease for years. The infantile form shows the first symptoms between the ages of six months and one year. Contrary to the infantile form, the others occur equally in boys and girls. The juvenile variant begins in the first or second decade of life. The adult form breaks out between the ages of 20 and 45.
There is no cure and no therapy is possible. Treatment only attempts to relieve or treat the symptoms of Alexander disease. It is carried out with antiepileptics, antispasmodics or anticonvulsants and painkillers. Difficulty feeding due to the dysphagia associated with the disease requires the placement of a nasogastric tube in some patients.
Other measures include physiotherapy, ergotherapy and speech therapy. Physiotherapy relieves limb cramps. In any case, not only the patient is being treated, but also the affected family members need supportive advice.
Outlook & Forecast
The prognosis for Alexander’s disease is generally poor. According to the current state of research, a cure is impossible. Affected children usually die within the first ten years of life. The specific prognosis of the patient depends primarily on the form and age of onset of the disease.
After the outbreak of Alexander’s disease, severe multiple disabilities develop within a few months or years, leading to death from cardiovascular failure. The disease progresses most rapidly in the neonatal form. The affected children usually die in infancy. The juvenile form of Alexander’s disease is somewhat milder. Neurological deficits only appear much later. Symptoms such as seizures and spasticity also appear much later or not at all with this form. In the long term, the disease also leads to the death of the patient in this form.
No concrete statements can be made about the prognosis of the adult form of Alexander’s disease. As a rule, it is much milder than the forms of the disease in childhood. There are often long-lasting courses with initially only minor impairments such as swallowing and speech disorders.
Prevention
Since a mostly spontaneous mutation is responsible for Alexander’s disease, there are no preventive measures. According to scientific assumptions, the probability that parents of affected children will have another child with this mutation is one percent. Nevertheless, if the disease occurs in the family, doctors recommend genetic counseling and prenatal diagnostics.
Aftercare
Alexander’s disease is an incurable disease that is usually fatal. Aftercare focuses on caring for the remaining loved ones after the death of the child. The doctor establishes contact with a suitable therapist and a self-help group. It is important to process the grief in order to regain quality of life. It is also important to understand the disease.
In addition, general measures such as exercise and rest help to process the trauma. Which of these make sense for the individual in detail must be discussed with the responsible doctor. Aftercare in the true sense does not exist with Morbus Alexander. If the parents decide to have another child, a genetic test can be carried out.
The genetic test is used to estimate the risk of the second child developing the disease. The possibilities are discussed with the parents during the subsequent consultation. If the risk of the disease is high, another pregnancy does not make sense. If the risk is low, the parents-to-be must also be closely monitored.
You can do that yourself
Alexander’s disease is a serious disease that cannot be treated causally. The parents of affected children should seek therapeutic support at an early stage. In a self-help group for affected parents, the relatives learn how to deal with the illness and to process the mostly negative course.
An important accompanying measure is physiotherapeutic treatment, which the parents can continue at home. Physiotherapy and ergotherapy cannot solve the symptoms, but they can slow down the course of the disease. In addition, physical exercise and support increase the quality of life of the child. Equally important is close monitoring by the doctor. Parents should also watch carefully for any unusual symptoms and call emergency medical services if in doubt. Depending on the type and severity of Alexander’s disease, appointments with a speech therapist and other specialists must be organized and the necessary aids purchased.
People suffering from the adult form of Alexander’s disease should also consult a psychologist. Initially, the progression of the disease can be slowed down by exercise and dietary measures. If the disease occurs in the family, genetic counseling is recommended.
