Alexander disease is a very rare fatal disorder 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 disease?
Pathologist William Stewart Alexander first described Alexander disease as a disorder. It is one of the leukodystrophy disorders. 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. Alexander’s disease differs from the other leukodystrophy disorders in that special tissue cells in the nervous system, the astrocytes, are affected by Rosenthal fibers. The Rosenthal fibers are worm-like inclusions in the cell. The disease is divided into four forms, depending on the age of the affected person. The infantile form is the most common. It occurs in infants. There is also the neonatal form in newborns, the juvenile form in adolescents, and the adult form in adults. Sometimes scientists use the name Alexander’s disease only for the infantile form. Boys suffer from the infantile form more often than girls. The rarity of this disease is reflected in the fact that doctors estimate the number of scientifically studied sufferers worldwide at about 150 people. In Germany, there were only 50 proven cases in 2011.
Causes
The disease is due to a genetic mutation. The gene for the production of 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 originate predominantly from the father’s genes. How this change in the gene leads to the degeneration of the nerve cells and causes the typical changes in the brain has not yet been clarified.
Symptoms, complaints, and signs
The disease manifests itself differently depending on age. In the infantile form, there are marked developmental disturbances in motor and sensory function. In addition, there are disturbances in motor coordination. In addition to enlargement of the skull, another symptom is enlargement of the brain. Affected individuals have difficulty swallowing and suffer from spasticity, which is the contraction of individual muscles or muscle groups, and seizures. In the neonatal form, the same symptoms occur and intensify over a much shorter period of time. The symptoms of the juvenile form are case dependent. Not all signs of the disease appear. Sometimes juvenile patients do not have seizures and do not suffer from spasticity. The enlargement of the skull known as macrocephalus is also less common in sufferers of the juvenile form. The typical symptoms of Alexander disease occur much less frequently and in milder forms in the adult form. However, doctors have found that in adults, the brainstem is affected to a greater extent by the destruction. Speech disorders and involuntary twitching of the uvula occur.
Diagnosis and course of the disease
Alexander disease is a disease that is fatal. It causes severe disability and ends in cardiovascular failure. After discovery of the disease, it was initially common to make a diagnosis by biopsy, the removal of a tissue sample. Meanwhile, magnetic resonance imaging of the brain is performed to verify the diagnosis of a juvenile form. To consider the diagnosis confirmed, 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 fringe. This shows darker or lighter zones in certain areas of the brain, depending on the imaging type of the scan, which do not have this color gradation in normal development.
- Similarly, the enrichment of certain brain regions with contrast agent is an indication of the disease.
- The fourth criterion is anatomical abnormalities in the thalamus, brainstem and 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
Due to Alexander’s disease, the patient experiences very serious symptoms and complications in everyday life. As a rule, various motor disorders occur, so that the deforestation of the child is significantly limited. Also the coordination and the movement of the patient is limited by Alexander’s disease, so that the patients are also dependent on the help of other people in their everyday life. Furthermore, there are difficulties in swallowing and the development of spasticity. The swallowing difficulties can also lead to difficulties in taking food or liquids. Not infrequently, the parents of those affected are also severely affected by Alexander’s disease and suffer from psychological complaints or even depression. In the further course of the disease, speech disorders occur, which can also lead to bullying or teasing among children. The patient’s quality of life is considerably reduced by Alexander’s disease. The life expectancy of the affected person is also reduced by the disease, so that it finally comes to the death of the affected person due to heart failure. Treatment of the disease can only reduce the symptoms, but cannot solve them completely. Furthermore, the relatives or the parents not infrequently need psychological treatment to cope with the psychological stress.
When should one go to the doctor?
If developmental disorders in various areas are noticed in a growing child, a doctor should always be consulted. In the case of physical as well as mental abnormalities, it is advisable to conduct a medical examination so that a clarification of the symptoms can be made. Disturbances and irregularities of the movement sequences, the motor function as a whole as well as the sensorimotor function should be examined and treated. If behavioral abnormalities and inconsistencies in locomotion occur in direct comparison to children of the same age, medical help is needed. Since Alexander’s disease has a fatal course, a visit to the doctor should be made at the first signs and suspicion of a possible health problem. Through an individual treatment and therapy plan, existing symptoms can be taken care of medically and thus the quality of life of the sufferer can be improved considerably. In case of speech disorders, convulsions, a seizure disorder or spasticity, a visit to the doctor is necessary. If there are abnormalities of the muscular system, contractions of individual muscle fibers or if an enlarged head shape is noticed, 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 physician immediately. Disorders of voluntary movement are further indications of a present disease. In particular, an irregularity of the uvula indicates Alexander’s disease and should be presented to a physician.
Treatment and therapy
The various forms progress with varying duration and severity. Infants with the disease die after a few months. Adults, children, and adolescents may live with the disease for years. The infantile form shows its first symptoms between six months and one year of age. Contrary to the infantile form, the others occur equally in boys and girls. The juvenile form 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 available. Treatment attempts only to alleviate or treat the symptoms of Alexander disease. It is done with antiepileptic drugs, antispastic drugs, or anticonvulsant and analgesic drugs. Difficulties in eating due to the swallowing difficulties associated with the disease require the placement of a feeding tube in some patients. Other measures include physiotherapy, occupational therapies and speech therapy. Physiotherapies relieve cramping of the limbs. In any case, not only is the patient in need of treatment, but affected family members also need supportive counseling.
Outlook and prognosis
The prognosis for Alexander disease is generally poor. According to current research, a cure is impossible. Affected children usually die within the first ten years of life. The specific prognosis of the affected individual depends primarily on the form and age of onset of the disease.After onset of Alexander’s disease, severe multiple disabilities develop within a few months to years, leading to death from cardiovascular failure. The disease progresses most rapidly in the neonatal form. Affected children usually die while still infants. The juvenile form of Alexander’s disease is somewhat milder. In this case, neurological deficits do not appear until much later. Symptoms such as seizures and spasticity also occur considerably later or not at all in this form. In the long term, this form of the disease also leads to the death of the patient. No concrete statements can be made about the prognosis of the adult form of Alexander’s disease. As a rule, its course is much milder than that of the childhood forms of the disease. Thus, there are often long-lasting courses with only minor impairment at first, such as swallowing and speech disorders.
Prevention
Because Alexander disease is caused by a mostly spontaneous mutation, there are no preventive measures. According to scientific assumptions, the probability that parents of affected children will have a child with this mutation again is one percent. Nevertheless, doctors recommend genetic counseling and prenatal diagnosis if the disease occurs in a family circle.
Follow-up
Alexander disease is an incurable condition that is usually fatal. Follow-up care focuses on caring for the remaining family members after the child’s death. The physician establishes contact with an appropriate therapist and support group. The aim is to work through the grief in order to regain quality of life. Understanding the disease is also important here. In addition, general measures such as sports and rest help to process the trauma. Which of these make sense for the individual in detail must be discussed with the responsible physician. There is no follow-up care in the true sense of the word for Alexander’s disease. If the parents decide to have a child again, a genetic test can be performed. The genetic test assesses the risk of disease in the second child. During the subsequent consultation, the options are discussed with the parents. If the risk of disease is high, a new pregnancy is not advisable. If the risk turns out to be low, the expectant parents must also be closely monitored.
What you can do yourself
Alexander disease is a serious condition that cannot be treated causally. 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 disease and process the usually negative course. An important accompanying measure is physiotherapeutic treatment, which can be continued by the parents at home. Although physiotherapy and occupational therapy cannot solve the symptoms, they can slow down the course of the disease. In addition, physical exercise and encouragement increase the child’s quality of life. Close monitoring by the doctor is equally important. Parents should also watch carefully for unusual symptoms and, if in doubt, call emergency medical services. Depending on the type and severity of Alexander’s disease, appointments with a speech therapist and other specialists may need to be arranged and necessary assistive devices purchased. Individuals suffering from the adult form of Alexander’s disease should also see a psychologist. At the beginning, the progress of the disease can be slowed down by sports and dietary measures. When the disease occurs in a family circle, genetic counseling is recommended.
