Is CADASIL a Terminal Illness?

Migraines accompanied by auras due to blood vessel damage are the first symptoms of CADASIL. Other common symptoms include strokes, transient ischemic attacks in the subcortical area, and mood disorders.

CADASIL syndrome is associated with dementia. After the early stages, CADASIL can progress to subcortical dementia and cause

• Urinary incontinence
• The inability to walk
• Pseudobulbar palsy
• Psychiatric issues (such as depression, anxiety, and apathy) occur in about 30 percent of people diagnosed with CADASIL
• Seizures or epilepsy in about 10 percent of middle-aged people with CADASIL
• Diffusion of white matter lesions with subcortical infarcts on neuroimaging

Some rare signs and symptoms of CADASIL

• Parkinsonism (slow movements with tremors in some parts of the body, mostly the legs) 
• Frequent amnesia
• Neuropathological issues, such as the dysfunction of one or more of the peripheral nerves, which leads to numbness or weakness
• Myopathy (characterized by weakness of the muscles due to a muscular disorder)
• Coma, confusion, lack of concentration, and fever
• Involvement of the spinal cord
• Nausea
• Vomiting
• Abnormal eye proteins
• Head motion intolerance
• Acute vestibular syndrome and rapid vertigo over a period

CADASIL is caused by mutations in the NOTCH3 gene. The NOTCH3 gene encodes the NOTCH3 receptor protein, which plays a crucial role in the survival of vascular smooth muscle cells. In response to certain molecules binding to NOTCH3 receptors, these cells send signals to their nuclei. The signals activate certain genes within smooth muscle cells in the vascular system.

• NOTCH3 gene mutations produce abnormal NOTCH3 receptor proteins, impairing the function and survival of vascular smooth muscle cells. A disruption of the NOTCH3 function can result in the self-destruction (apoptosis) of these cells. The loss of vascular smooth muscle cells causes blood vessel damage in the brain, causing CADASIL.
• The disease is inherited in an autosomal dominant pattern, which means that each cell must contain one copy of the altered NOTCH3 gene. An affected person inherits the mutation from one affected parent most of the time.
• Spontaneous mutations in the NOTCH3 gene could happen without any familial involvement.

A diagnosis of CADASIL is based on symptoms, family history, and brain MRI lesions that are consistent with the disease.

Although MRI can identify characteristic changes in the brains of people with CADASIL, such changes are not unique to CADASIL and can occur with other conditions as well.

CADASIL diagnosis can only be confirmed by

• DNA testing of blood samples for mutations in the NOTCH3 gene
• Identifying granular osmiophilic material inclusions on a skin biopsy

There is no cure for CADASIL, and treatment options are limited. However, there are several ways to manage the condition and help alleviate symptoms. These may include

• Medications: Prevent or manage stroke-like episodes and include blood thinners, blood pressure medications, and cholesterol-lowering drugs.
• Physical therapy: Can help improve mobility, strength, and balance and reduce the risk of falls.
• Occupational therapy: Help individuals with CADASIL maintain independence in their daily activities and improve their quality of life.
• Speech therapy: To help with any communication difficulties that may arise as a result of CADASIL.
• Psychological support: Living with CADASIL can be emotionally challenging, and support from a mental health professional could be helpful.
• Genetic counseling: Help individuals with CADASIL understand the genetic basis of their condition and the risks to family members.

The life expectancy of people with CADASIL can vary widely. Many people live well into old age.

The severity of the disease and complications can affect life expectancy. Some people with CADASIL may experience severe and progressive neurological problems, including recurrent strokes, and severe cognitive decline, which can significantly reduce their life expectancy.

The exact mortality rate for people with CADASIL is not known, but the age range for stroke is between 45 and 50 years. A person with CADASIL on average lives for 61 years.