CADASIL is a rare genetic disease that affects the muscular walls of the small arteries that supply blood to the brain. The acronym CADASIL stands for autosomal dominant cerebral arteriopathy with subcortical infarcts and leukoencephalopathy. The disease is the result of mutations in the NOTCH3 gene.
Among the most prominent symptoms are the presence of migraine with aura, psychiatric disorders and the occurrence of ischemic strokes. Over time, most people affected by CADASIL become bedridden and develop dementia. Unfortunately, there is no cure for the disease. Treatment consists of controlling factors that may further aggravate small arteries, reduce symptoms and provide emotional support and counseling for those affected and their relatives.
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Summary about CADASIL
- CADASIL is a rare genetic disease that affects the small cerebral arteries.
- CADASIL is an acronym for autosomal dominant cerebral arteriopathy with subcortical infarcts and leukoencephalopathy.
- The disease is caused by mutations in NOTCH3, a gene responsible for containing the necessary information for the production of a protein expressed in smooth muscle cells in the walls of small arteries.
- The age of onset, symptoms, and progression of CADASIL vary among affected individuals.
- The main symptoms include migraine with aura, ischemic strokes, psychiatric disorders and cognitive decline.
- Most people develop dementia over time, and the life expectancy of individuals affected by the disease is reduced.
- Diagnosis involves MRI scans and genetic tests, as well as analysis of the patient's family history.
- There is no cure for the disease, and treatment aims to manage symptoms and control risk factors that may affect small arteries, such as diabetes and smoking.
What is CADASIL?
CADASIL é a disease genérare condition that affects small arteries dthe white substance of the brain. The term was first used in 1993 and constitutes an acronym in English that means:
- Cerebral (cerebral): related to the brain.
- Autosomal (autosomal): refers to autosomal inheritance, where genes are located on non-sex chromosomes.
- Dominant (dominant): represents the form of inheritance in which only one abnormal copy of a gene is necessary for the development of a disorder.
- Arteriopathy (arteriopathy): indicates a disease that occurs in the arteries.
- Subcortical (subcortical): related to specific areas of the brain supplied by small, deep blood vessels.
- Infarcts (heart attacks): refers to the loss of tissue in the brain caused by a lack of blood flow, which occurs when circulation through small arteries is severely reduced or stopped.
- Leukoencephalopathy (leukoencephalopathy): represents lesions in the white matter of the brain caused by the disease and seen on MRI scans.
In Portuguese, the full translation of the acronym is: autoss cerebral arteriopathyôdominant mica with subcortical infarcts and leukoencephalopathy. CADASIL is also known as hereditary multi-infarct dementia.
CADASIL affects men and women equally and is found throughout the world. However, the difficulty in diagnosing the disease makes it difficult to determine its real prevalence in the general population. Estimates indicate that the disorder occurs in approximately 2 to 5 out of every 100,000 people.
Causes of CADASIL
CADASIL occurs mainly fromI see the inheritance autosôdominant mica. Therefore, in most cases, the affected person has one of their parents with the disease. However, in rare cases, the disorder may appear due to a spontaneous genetic mutation that occurs for unknown reasons.
That occurs due to mutations in the gene NOTCH3, responsible for containing the information necessary for the production of the NOTCH3 protein expressed in smooth muscle cells in the walls of small arteries.
Mutations in this gene result in the abnormal accumulation of this protein on the surface of these cells, resulting in progressive damage to the small arteries of the brain, destruction premature development of smooth muscle cells and narrowing of the lumen, thickening of the walls of small arteries and accumulation of granular osmiophilic material (protein debris) in the arteries. These changes reduce blood flow to the brain, leading to small strokes, dilated spaces around the vessels and loss of tissue on the surface of the brain (cortex) and under the cortex (region subcortical).
CADASIL symptoms
The age of onset, symptoms and progression of the disease vary widely from one person to another. Symptoms usually appear between the ages of 20 and 40, although they can also appear later in life. The main symptoms of CADASIL include:
- Migraine (usually accompanied by aura)
- Multiple ischemic strokes (brain stroke that occurs when a blood vessel supplying blood to the brain is obstructed)
- Seizures
- Cognitive decline
- Vision problems
- Psychiatric disorders, such as apathy and depression
- Weakness
Over time, even around the age of 65, most people affected by CADASIL become bedridden, experience cognitive problems and develop dementia.
Also access: Dementia — term that groups a group of neurodegenerative diseases
CADASIL diagnosis
The diagnosis of CADASIL begins with the history evaluationrich family and symptoms, in addition to identifying brain lesions characteristic of the disease by performing MRI examsncia magnéethics. However, since some symptoms and lesions identified are not exclusive to the disease, it is necessary to resort to other methods to confirm the diagnosis. In this sense, they are used DNA tests on blood samples to identify characteristic mutations in the NOTCH3 gene or search for inclusions of granular osmiophilic material (GOM) in a biopsia.
Does CADASIL have a cure?
CADASIL is a disease that yetThere is currently no cure. Treatment aims to help manage this condition.
CADASIL treatment
CADASIL treatment consists mainly of control of factors that can further harm blood vesselsneos, such as hypertension, diabetes, high cholesterol, obstructive sleep apnea and smoking.
Furthermore, we seek to minimization of symptoms resulting from the diseaseThe, such as migraine, through the use of medications. Due to the lack of a cure or effective treatment, part of the treatment is aimed at psychological support, both for patients and their families.
Life expectancy at CADASIL
The life expectancy of a person with CADASIL can vary, as the disease affects individuals differently, and factors such as early diagnosis and management of coexisting medical conditions can influence it.
In general, research shows that CADASIL can lead to a reduction in life expectancy, mainly due to the increased risk of stroke and associated complications.
CADASIL Prevention
At the moment, There is no treatment that can prevent the onsetcio da CADASIL, just measures that help manage the disease and reduce the risk of complications.
Image credit
[1]Wikimedia Commons(reproduction)
Sources
CHABRIAT, H. et al. 2004. CADASIL: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy. Mohr, J. P. et al. (Ed.). stroke: pathophysiology, diagnosis, and management. London: Churchill Livingstone. 2004:687-692.
HACK, R.J. et al. 2000 [revised 2019]. CADASIL. Adam, M. P. et al. (Ed.). GeneReviews® [Internet]. Seattle (WA): University of Washington. Available in: https://www.ncbi.nlm.nih.gov/books/NBK1500/.
NINDS - National Institute of Neurological Disorders and Stroke. 2019. CADASIL Information Page. Available in: https://www.ninds.nih.gov/Disorders/All-Disorders/CADASIL-Information-Page.
NORD - National Organization for Rare Disorders. 2019. CADASIL. Available in: https://rarediseases.org/rare-diseases/cadasil/.
WANG, M. M. 2018. CADASIL. Handb Clin Neurol. 148: 733-743.
