CADASIL is a disease whose development is genetic and is associated with clustered strokes in affected individuals. The disease term CADASIL is derived from English and stands for Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy. The infarcts arise primarily in middle age.
What is CADASIL?
CADASIL is a hereditary disease that results in familial clustered infarcts in patients. In CADASIL, an autosomal dominant inheritance is present. CADASIL is one of the cerebral arteriopathies, with subcortical infarcts in addition to leukoencephalopathy. Unlike most other strokes due to arteriosclerosis or similar pre-existing conditions, in CADASIL a genetic mutation is responsible for the susceptibility to infarction. Specifically, a mutation on the NOTCH3 gene leads to the symptoms of CADASIL. The gene is located on a specific arm on the 19th chromosome. As a result of the gene mutation, patients with CADASIL suffer from a microangiopathy that affects major arteries in the brain. The first signs of CADASIL often consist of severe and recurrent headaches that resemble migraines. This pain is caused by typical changes in the blood vessels as a result of the disease. Generally, CADASIL is considered a rare disease. However, it is comparatively common among hereditary stroke diseases, with a prevalence of about 5:100,000.
Causes
CADASIL develops as a result of genetic mutations on the NOTCH3 gene. In CADASIL, there is basically an autosomal dominant pattern of inheritance. The responsible gene is located on the short branch of the 19th chromosome. Because of the hereditary predisposition, the typical infarcts in CADASIL occur more frequently in affected families.
Symptoms, complaints, and signs
Due to CADASIL, patients initially suffer recurrent minor strokes over a period of several years. These primarily damage the white matter of the brain. As a result of these infarcts, people suffering from CADASIL develop increasing dementia. As a result, the mental abilities of the affected individuals gradually decline more and more. On clinical examination, CADASIL may show parallels to Binswanger’s disease. However, patients suffering from CADASIL do not suffer from hypertension. In principle, the course of CADASIL differs greatly between individuals as well as within affected families. In principle, typical symptoms associated with small strokes are seen. CADASIL hardly affects life expectancy, especially in female patients. Some carriers of the gene mutations do not suffer from any symptoms of CADASIL until the end of their lives. In advanced stages, CADASIL causes increased dementia symptoms as well as movement and spasticity disorders. In the final stage of CADASIL, patients lie in a vegetative state and are dependent on artificial nutrition. In principle, CADASIL often affects other arterioles in various organs and is thus not inevitably limited to the brain. For example, the eyes are affected by abnormalities, with changes mainly in the retina. However, the abnormalities usually do not cause symptoms. The skin may also be affected by changes due to CADASIL. In rare cases, limitations in the function of the kidneys develop due to CADASIL. In these cases, patients also suffer from microhematuria as well as mild proteinuria.
Diagnosis and course
Family history is of great importance in the diagnosis of CADASIL. In addition, an accurate description of the previous course of the disease is of enormous importance. To diagnose CADASIL, the physician uses imaging techniques, such as MRI or CT scans. Often, a diagnosis of CADASIL is made only after strokes have occurred. The typical headaches theoretically indicate CADASIL before then, but some physicians confuse the pain with migraine. However, earlier diagnoses are possible in children of affected individuals. A reliable diagnosis of CADASIL is generally made by genetic testing, whereby physicians identify the triggering gene. As part of the differential diagnosis, the physician clarifies whether other leukoencephalopathies, such as Fabry disease or CNS vasculitis, are present.Leukodystrophies such as metachromatic leukodystrophy should also be excluded. In addition, CADASIL should not be confused with the disease CARASIL.
Complications
CADASIL causes the patient to have an infarction at a relatively early stage. In the worst case, this can lead to the death of the patient. Infarcts also often lead to severe and irreversible sequelae, for which no direct treatment is possible. Strokes primarily damage the brain. Sensory disturbances and restrictions of the motor function occur. Furthermore, dementia can occur, whereby the affected person is also restricted in his thinking and acting. It is not uncommon for CADASIL to cause speech and behavioral disorders. The quality of life is extremely reduced by this disease. As the disease progresses, various spasticities occur, so that the patient may be dependent on care from other people or on artificial feeding. Internal organs may also be damaged, which also reduces the patient’s life expectancy. The eyes are also affected by CADASIL, so loss of vision occurs. It is not possible to treat CADASIL causally. For this reason, treatment is aimed only at reducing the infarct. High blood pressure must be avoided and the affected person must lead a healthy lifestyle. Further complications usually do not occur.
When should you go to the doctor?
A doctor must be consulted for recurrent migraine-like headaches. The latter can determine whether these complaints represent an early symptom of CADASIL or are due to another condition. Immediate treatment is required in any case. Possible early symptoms also include: kidney dysfunction, problems with vision, and signs of dementia. If these warning signs are noticed, a visit to the doctor is required. If a stroke occurs, an emergency physician must be consulted immediately. Recurrent strokes, which are also accompanied by the aforementioned accompanying symptoms, are a sure sign of the genetic disease and should be treated in any case. At the latest, when the mental abilities of the affected persons decrease, a CADASIL disease can be assumed. Further warning signs that require immediate clarification by a physician are disturbances of movement and spasticity. Due to the multitude of possible symptoms and the varying course the disease can take, a specific diagnosis is usually only possible in the late stages. A family history can provide information about any risk of the disease and thus enable early diagnosis and therapy.
Treatment and therapy
Causative treatment as well as a cure for CADASIL is not yet possible. Patients usually receive medications to reduce acute symptoms and decrease the risk of stroke. In this course, lifestyle changes are usually useful to minimize certain risk factors. For example, physicians aim for low blood pressure and low blood lipids and blood sugar levels when treating CADASIL. However, the course of CADASIL can hardly be influenced. It is therefore also important that patients prepare an advance directive in good time in case the disease progresses to the terminal stage. The limited ability to influence the progression of CADASIL often makes early diagnosis unnecessary, as it only increases the psychological suffering of affected patients for no reason.
Outlook and prognosis
In the worst case scenario, CADASIL can lead to the death of the affected individual, as the patient suffers a stroke. Usually, this occurs when the disease is left untreated. In this case, treatment is done by taking medications that can reduce the risk of stroke. Likewise, a healthy lifestyle can have a positive effect on the course of the disease and prevent strokes. The course of CADASIL depends very much on the type of treatment and the patient’s lifestyle. Often, however, the course of CADASIL cannot be influenced, as the disease has been little researched so far. However, early diagnosis has a very positive effect on the patient’s condition in any case. Since the symptoms of CADASIL often appear at a young age, the life expectancy of those affected is greatly reduced. If CADASIL is not treated, most patients die of a stroke or its consequences.The consequences of a stroke are often irreversible and can no longer be treated. The disease progresses despite treatment and unfortunately cannot be stopped.
Prevention
Preventive measures regarding CADASIL are not yet available. CADASIL is fixed at birth, so preventive agents would have to target genetic mutations. Susceptibility to stroke from CADASIL is reducible by lifestyle changes, so prevention is partially possible here.
Follow-up
Because CADASIL is a hereditary disease, it also cannot be cured causally or completely. Follow-up care is also not possible in this case, so the affected person is dependent on treatment throughout his or her life. Since CADASIL leads to an increased risk of strokes, these must be prevented. This is possible above all through a healthy lifestyle. In the event of a stroke, a hospital should be visited immediately or an emergency doctor should be called. Often, after a stroke, therapy is also necessary to compensate for possible disabilities. Strokes can occur frequently, especially in middle age. After the stay in the hospital, the affected person is usually dependent on taking medication. These should be taken regularly and in the correct dosage. Some consequences of strokes are unfortunately irreversible and cannot be fully treated. The risk of another stroke is significantly reduced by a healthy lifestyle and by taking the medication. If the patient’s parents wish to have another child, they should undergo genetic counseling to possibly avoid the occurrence of CADASIL.
Here’s what you can do yourself
Patients suffering from CADASIL can take some steps themselves to relieve the symptoms. A change in lifestyle has proven to be effective. Affected individuals should avoid excess weight or reduce existing excess weight through diet and exercise. Physical activity and a balanced diet are important components of the accompanying therapy. Sufferers should also avoid smoking or stop smoking to prevent high blood pressure, cholesterol disorders and other complications that can have a negative impact on CADASIL syndrome. Other harmful influences such as diabetes or dyslipidemia should be avoided through an active lifestyle and regular medical checkups. Women should stop taking the pill or, if necessary, switch to a preparation with a low estrogen content. They should also drink plenty of fluids. Regular fluid intake is especially important in summer. The accompanying measures focus on preventing a stroke. If a stroke has already occurred, self-therapy focuses on supportive physiotherapeutic and mental measures. Which steps are useful and necessary in detail depends on the severity of the condition. In principle, a self-help group should be sought out, because talking to other sufferers is an important part of coming to terms with a stroke. In addition to therapy centers, Internet forums are also useful for this purpose.