Neurodegeneration with iron deposition in the brain represents a disease that occurs with a very low frequency. The disease is also often referred to by the abbreviation NBIA in international medical jargon. Neurodegeneration with iron deposition in the brain leads to neurological degeneration. A typical feature of the disease is primarily that iron is deposited in intercerebral areas, particularly in the so-called basal ganglia.
What is neurodegeneration with iron deposition in the brain?
The synonymous but now obsolete name for neurodegeneration with iron deposition in the brain is Hallervorden-Spatz syndrome. The disease is relatively rare, with a frequency of one to nine cases in one million people. Affected patients have detectable accumulations of iron in the brain, primarily concentrated in the basal ganglia. This is a special area within the human brain. Basically, neurodegeneration with iron deposition in the brain is a degenerative disease. The areas most affected by the deposits are the basal ganglia, in particular the so-called substantia nigra as well as the globus pallidus. Neurodegeneration with iron deposition in the brain is usually inherited to the offspring in an autosomal recessive manner. In principle, neurodegeneration with iron deposition in the brain is considered to belong to the category of so-called neuroaxonal dystrophies. The first description of neurodegeneration with iron deposition in the brain was made in 1922 by Hallervorden and Spatz. In reference to these two researchers, the disease was initially named Hallervorden-Spatz syndrome. Statistics show that about 45 people in Germany currently have neurodegeneration with iron deposition in the brain.
Causes
The causes of neurodegeneration with iron deposition in the brain are primarily genetic. Crucial to the development of the disease is a defect on a specific gene. Basically, neurodegeneration with iron deposition in the brain is passed on in an autosomal recessive manner. The gene responsible for the disorder is the so-called pantothenate kinase 2, which is located on the 20th chromosome. The corresponding protein is essential for the formation of coenzyme A. Disorders lead to accumulations of the substances panthetheine and cysteine. Both develop a toxic effect or form free radicals as soon as they come into contact with iron. In this way, the brain of the affected person is oxidatively impaired. Both iron and neuromelanin are deposited in relatively large amounts in the brain as part of neurodegeneration with iron deposition.
Symptoms, complaints, and signs
Neurodegeneration with iron deposition in the brain is associated with a variety of symptoms for affected individuals. In the majority of cases, the degenerative disease begins in childhood. Even in children younger than ten years of age, a typical combination of disease symptoms may be observed. On the other hand, it is also possible that neurodegeneration with iron deposition in the brain does not begin until adulthood. At the beginning there are usually disturbances of movement of extrapyramidal type. Particularly often, for example, there are disturbances of gait, with the affected persons tending to falls or a so-called leg dystonia. Psychological peculiarities occur less frequently. Later, the movement disorders expand to include symptoms such as tremor, dystonia and choreoathetosis. Rigid elevation of muscle tone, retardation, and hyperreflexia are also possible. In some circumstances, affected individuals show signs of dementia. Neurodegeneration with iron deposition in the brain is also often characterized by dysphagia and dysarthria. It is also typical that neurodegeneration with iron deposition in the brain is progressive. That is, the symptoms and health status of the diseased patients gradually worsen more and more.
Diagnosis and disease progression
When characteristic symptoms of neurodegeneration with iron deposition in the brain occur, an appropriate physician should be consulted immediately. At the beginning of the diagnosis, the attending specialist takes a so-called medical history, in which the patient reports on his or her complaints and general lifestyle.After that, the clinical symptoms and signs of the disease come into focus. Neurodegeneration with iron deposition in the brain can be diagnosed relatively reliably on the basis of various examinations. An MRI examination of the brain is often used for this purpose. A deposit of iron is visible in the area of the globus pallidus, which is also known as the ‘tiger’s eye sign’. In addition, within the framework of genetic analyses of the affected person, corresponding mutations may be detectable, which are suitable for the diagnosis of neurodegeneration with iron deposition in the brain.
Complications
Due to neurodegeneration with iron deposition in the brain, patients suffer from various symptoms. However, these usually depend greatly on the severity of the disease. In many cases, those affected suffer from gait disturbances and also movement restrictions. It is not uncommon for sufferers to fall and thus have serious accidents. Symptoms of dementia can also occur as a result of neurodegeneration with iron deposition in the brain, thus significantly restricting the daily lives of those affected. It is not uncommon for patients to be dependent on the help of other people as a result of the disease. Confusion and forgetfulness occur, so that the patient’s quality of life is also significantly reduced. If neurodegeneration with iron deposition in the brain already occurs in children, this disease also leads to considerable limitations and delays in the development of the child, so that complaints and complications can also occur in adulthood. Treatment of neurodegeneration with iron deposition in the brain is not possible. Individual complaints can be alleviated with the help of various therapies. Thereby no complications occur. However, a positive course of the disease cannot be predicted in every case.
When should one go to the doctor?
If growing children and adolescents show disturbances of the body structure or impairments of the movement processes, a visit to the doctor is advisable. Gait insecurities, limitations of natural joint movements or an increased risk of accidents and injuries should be examined by a physician. If the affected person can no longer participate in usual sports activities or leisure activities due to the existing complaints, there is cause for concern. If there is stiffening of the extremities, tremor or delay in natural reflex movements, a visit to the doctor is necessary. If there are behavioral abnormalities, listlessness or apathy, a physician is needed. If there are mood swings or other peculiarities of occurrence, as well as reduced performance, clarification of the existing complaints is necessary. Psychological stress may develop due to the physical irregularities, which should be treated at an early stage. The first signs are a diminished sense of well-being, a depressed mood, a withdrawal from social and societal life and an increased readiness for conflict. If the existing complaints slowly increase in intensity over several weeks and months, there is a need for action. A physician must be consulted so that an improvement in the quality of life can be initiated through a targeted therapy plan. If affected persons show confusion or changes in their usual ability to learn, these are worrying signs. They must be presented to a physician immediately.
Treatment and therapy
According to current research, there is not yet a causal treatment option for neurodegeneration with iron deposition in the brain. However, attempts have been made to treat the defect in the enzyme. Here, the active ingredient iron chelator Ferriprox is currently being tested. Hyperkinesia and dystonia may be relieved by deep brain stimulation. Benzodiazepines and baclofen are used in many cases to relax the muscles. These also serve to relieve pain at the same time.
Outlook and prognosis
In people with neurodegeneration with iron deposition in the brain, a genetic defect has been identified as the cause of the health impairments. This has the consequence that the prognosis is unfavorable. According to the current scientific and legal status, no modification of human genetics is allowed. Therefore, a cure for the disease can be ruled out to date.Researchers and treating physicians focus on providing the best possible therapy for the individually severe symptoms. The goal is to optimize the quality of life of the affected person. If medical help is not sought, this decision can lead to numerous complications. States of confusion and forgetfulness trigger severe problems in coping with everyday life. The affected person is dependent on the help and support of other people, as otherwise complete self-care cannot be adequately ensured. Due to existing disturbances of the balance as well as restrictions of the musculoskeletal system, the risk for accidents is increased. This can lead to secondary diseases and thus to further impairment of health. With an early diagnosis and an immediate start of therapy, numerous improvements in the general condition can be achieved. The treatment measures required are selected on an individual basis. What all patients have in common is that they require continuous medical treatment over the lifespan and receive long-term therapies.
Prevention
Neurodegeneration with iron deposition in the brain is a congenital disease based on a genetic defect or mutation. Therefore, effective prevention of the disease is not possible by currently available means.
Follow-up
Neurodegeneration with iron deposition in the brain cannot currently be treated curatively and therefore places high demands on follow-up care. Because the disease has an impact on all areas of life, follow-up care encompasses several areas. In general, the aim is to improve the quality of life of those affected. Depending on the symptoms, physiotherapy, speech therapy and occupational therapy are used in the long term. These therapies ensure that, among other things, movement functions, fine motor skills or speech functions are maintained or even improved to the extent possible. Many patients also require aids that have to be individually adapted over time. For example, in the case of incorrect posture or spasticity, aids (orthoses) are used to immobilize and stabilize the body and the corresponding joints. Orthoses also require constant monitoring and adaptation to the course of the disease. As the disease progresses, follow-up care is used to determine what additional aids may still be necessary. Appropriate medication must also be administered to relieve pain or reduce spasticity. This can sometimes take a long time to find the balance between drug combinations that are as effective as possible and those that have few side effects. Neurologically effective medications also require slow adjustment until they are fully effective. Follow-up care also includes psychological support for patients, which can help them cope better with the disease.
Here’s what you can do yourself
Since the disease is associated with limitations in movement, daily exercise sessions should be held to stabilize gait. Movement patterns as well as coordination should be encouraged and targeted. Although the disease has a progressive course, there is a possibility that these measures may delay the developmental progress. Neurodegeneration already occurs in childhood. In order to prepare patients for the further development of the disease, doctors and parents should provide the child with comprehensive information as early as possible. Open questions should always be answered honestly and comprehensively. Emotional and psychological support is important so that the patient can react well to events and difficult situations in everyday life. In addition, an exchange with other affected persons can be perceived as very helpful. Through self-help groups or internet forums, patients can communicate with each other and exchange important information. To strengthen mental power, it is helpful to build up a sense of achievement in other areas. The child’s zest for life and sense of well-being should be promoted through targeted leisure activities. Shared experiences help to create a sense of cohesion. Although the organization of leisure time must experience restriction, there are various options that can be used despite the illness. This directs the focus to areas other than the disease.