CADASIL-CARASIL

Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) and Cerebral Autosomal-Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CARASIL) are extremely rare genetic disorders.

CADASIL requires only one parent to have the condition in order for a child to inherit it. CARASIL requires both parents be carriers of the condition in order for symptoms to be present.

Both forms of the condition affect the blood vessels of the brain. As abnormal muscle cells surrounding the blood vessels gradually die off, the blood vessels themselves are damaged (arteriopathy). Damage to the blood vessels in the brain can lead to the brain tissues receiving too little blood to survive. Tissue death (infarcts) can occur beneath the outer layer of the brain (subcortical). This reduced blood flow and tissue death can result in damage to the protective material (myelin) that covers nerves and ultimately loss of the key connections between brain cells that underlie normal function.

The dominant form of the condition may be caused by a change in the NOTCH3 gene, which is involved in the functioning of muscles cells that make up walls of blood vessels, but may also be due to changes in genes that remain to be identified.

The recessive form of the condition may be caused by a change in the HTRA1 gene, which is involved in the formation of new blood vessels, but again, some cases arise from undiscovered gene mutations.

Symptoms

CADASIL/CARASIL are vascular cognitive impairments, and symptoms are a result of limited blood flow to the brain, often resulting in dementia.

Symptoms of the conditions include:

  • Decreased mental ability (thinking, understanding)
  • Changes in behavior
  • Changes in personality
  • Confusion

The most common symptoms specific to CADASIL are migraine headaches and repeated strokes that progress to dementia. Other symptoms may include:

  • Seizures
  • Vision problems
  • Severe depression

The most common symptoms of CARASIL are stiffness in the legs and difficulty walking. Other symptoms may include:

  • Increased muscle tone
  • Stroke episodes
  • Muscle spasms
  • Slurred speech
  • Loss of bladder control
  • Worsening movement problems
  • Difficulty controlling facial muscles and speaking (pseudobulbar palsy)

Other symptoms that are associated with CARASIL, which are sometimes dismissed at first, are:

  • Patchy hair loss
  • Inflammation of the spine (spondyloarthropathies), causing back pain or herniated discs

Symptoms of CARASIL may progress more rapidly than those of CADASIL.

 

Causes and Risk Factors

CADASIL and CARASIL are both caused by a gene mutation.

The genetic cause of many cases remain to be discovered. Some cases of CADASIL are  associated with changes in the NOTCH3 gene. This gene is involved with the functioning of muscle cells that make up the walls of blood vessels. Some cases of CARASIL may be caused by a change in the HTRA1 gene, which is involved in the making of new blood vessels.

CARASIL is so rare that only 50 cases have been identified, and most of these have been in Japan and China. The reported cases have affected more men than women. CADASIL, on the other hand, affects men and women equally.

Both conditions usually are diagnosed during mid-adulthood, between the ages of 20 and 50, though some patients do not show symptoms until later in adulthood. Most CADASIL patients are diagnosed by the time they are 40; most CARASIL patients are diagnosed by the time they are 30.

Patients who have CADASIL or CARASIL in their family are at an increased risk of developing the condition. Patients with CADASIL may also be at an increased risk of a heart attack.

Diagnosis

Diagnosis of these conditions usually begins with a physical exam and a review of the patient's medical history and symptoms. The only way to positively diagnose either condition is through genetic testing. Imaging tests may also be used to help diagnose the condition and better understand the patient's symptoms.

Magnetic resonance imaging (MRI) can help the medical team look for areas of the brain that resemble stroke conditions and help determine if neurological deterioration has occurred.

The genetic test for CADASIL was not available until the year 2000. Prior to the test being available, the condition often was misdiagnosed as multiple sclerosis, Alzheimer's disease or other neurological conditions.

Treatments

There is no cure for CADASIL or CARASIL. Treatment for the condition focuses on managing patient symptoms.

Migraine headaches and seizures associated with CADASIL may be treated using medications. Patients may be instructed to take aspirin daily to help lower their risk of a heart attack or stroke. If the patient has other stroke risk factors such as smoking or uncontrolled high blood pressure or diabetes, these conditions should be managed to limit the risk of stroke.

For patients who have experienced a stroke, the Stroke Program at Cedars-Sinai provides a multidisciplinary treatment approach and a personalized treatment plan tailored to each patient. Patient care is generally broken down into three categories: stroke prevention, treatment immediately after a stroke, and post-stroke rehabilitation.

Patients with CARASIL may need physical and occupational therapy as part of their treatment.

For patients with a hereditary condition, genetic counseling, available through the Cedars-Sinai Medical Genetics Institute, can help identify families at risk and provide referrals to specialized health care providers.