Understanding CARASIL

CARASIL is a very rare, inherited disorder that affects small blood vessels in the brain and is caused by mutations in the HTRA1 gene. CARASIL stands for Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy. Although the name is complicated, its components are straightforward:

• Cerebral - means brain
• Autosomal recessive - means you need a mutated (faulty) copy of the gene from both parents
• Arteriopathy - means the small blood vessels are diseased
• Subcortical infarcts are small strokes deep within the brain
• Leukoencephalopathy - means damage to the brain’s white matter, which is very important for communication within the brain and with the rest of the body

CARASIL is a complicated disorder that can cause you to suffer from a range of symptoms. The symptoms usually begin in early adulthood, typically between the ages of 20 and 30.¹ It is extremely rare. We do not know exactly how common the condition is, although roughly 50 cases have been reported, predominantly in Japan and China.²

There is currently no specific treatment for CARASIL. Instead, different specialists, including neurologists, orthopaedics and psychiatrists, work together. A multidisciplinary approach can help manage symptoms more effectively and support a better quality of life.

Symptoms of CARASIL

• Stroke-like episodes: Small strokes can occur deep in the brain, leading to a gradual loss of function
• Motor problems: Stiffness, weakness, and difficulty walking are common. This is due to the condition that affects the nerves and muscles
• Cognitive decline: An individual may experience problems with memory, concentration, and reasoning, and may develop dementia
• Mood and personality changes: Some may experience irritability, emotional outbursts, and other personality changes
• Premature baldness: Hair loss is often the first symptom and is prevalent in around 90% of patients²
• Back pain and spine issues: Many develop chronic low back pain due to early spinal wear and tear (spondylosis)

Why a team approach matters

Clinical management of CARASIL depends heavily on symptom-based and supportive therapy. However, there is ongoing research into a treatment that targets the root of CARASIL, specifically gene-mutation correction. Because CARASIL can present with a wide range of symptoms, individuals can benefit from several specialists working together to manage their care. Such specialist includes:

• Neurologists - to help manage strokes, stiffness, and cognitive decline
• Orthopaedics - to treat spine and bone pain
• Psychiatrists - to support mood regulation and emotional well-being
• Physiotherapists – to help manage movement issues, to maintain an individual's independence for as long as possible
• Genetic counsellors – to confirm diagnosis, and help families and individuals understand the condition better

In general, supportive measures include providing education about the condition, emotional support, walking aids, medical treatment for spasticity, mood stabilisers and appropriate management of psychiatric manifestations. ¹

This kind of multidisciplinary care, in which doctors, therapists, patients, and families work together, ensures that all aspects of the condition are addressed.

The neurologist’s role

The neurologist plays the biggest role in caring for people with CARASIL, as the condition mainly affects the brain and nerves. Diagnosis often begins with brain scans (such as an MRI) that reveal changes, such as small strokes deep in the brain andwhite matter damage. ³ At this point, genetic testing is used to confirm mutations in the HTRA1 gene, which is the only reliable way to distinguish CARASIL from other conditions. Once diagnosed, the neurologist focuses on managing symptoms and preventing future strokes. The neurologist is so important because around 50% of patients suffer repetitive ischemic strokes, with the remaining 50% showing a stepwise deterioration, which is associated with vascular dementia. Both cases lead to a worsening in cognition over time.² These symptoms usually start in early adulthood, with a mean age of onset of around 32 years. ²

Treatment may include blood-thinning medications such as aspirin to help prevent further strokes and improve blood flow, although it is still unclear whether these drugs are usefulor necessay for CARASIL.⁴

Supportive care also involves medications to reduce muscle stiffness (spasticity).¹ Neurologists monitor changes in mental functioning, such as forgetfulness or difficulty processing information, as well as speech difficulties, helping patients manage these symptoms. By working closely with physiotherapists and other specialists, neurologists can also support movement and daily functioning for as long as possible, thereby improving overall quality of life.

The orthopaedic specialist’s role

Orthopaedic specialists play an important role in caring for people with CARASIL because the condition often causes early and persistent spine and joint problems. Around 80% of patients experience chronic low back pain, usually beginning in their twenties or thirties, and in some cases as early as early teenage years.^3,5

These problems are caused by early wear and tear in the spine - either spondylosis (breakdown of the vertebrae) or disc degeneration (damage to the soft discs between the vertebrae). These spinal changes can be seen on MRI scans around age 30, typically longafter symptoms first appear. ⁶

Disc degeneration and herniation (slipped disc) can be seen on scans. The spinal disc may press on the nerves,  worsening stiffness or mobility problems. In some rare, severe cases, surgery may be required to relieve pressure on the spine. ⁵ Supportive care also includes managing back pain. In one case, a person’s back pain improved partly with pain-relieving medication and physiotherapy.¹

Orthopaedic doctors assess back pain, posture, and movement difficulties. They recommend supportive treatments such as physiotherapy, gentle exercise, and walking aids to relieve pain and improve mobility. Working closely with physiotherapists, orthopaedic specialists aim to keep patients as mobile and comfortable as possible, helping them stay active and independent for as long as they can.

The psychiatrist’s role

Psychiatric care is a vital but often overlooked part of managing CARASIL. Around one-third of people with CARASIL begin experiencing mood changes around the age of 30.⁴ Personality changes, such as irritability or sudden mood swings, often appear at the very early stages of the condition.² Some case reports mention depression, anxiety, and sleep problems, but these are not defining features of CARASIL.² Instead, they are likely due to the emotional stress of living with a rare, progressive condition that slowly affects independence and quality of life. As memory and cognitive abilities also decline, all of these changes can be distressing for both the person and their family.

Psychiatrists play a key role in targeting these challenges. They may prescribe medications to help stabilise mood and provide counselling to support emotional well-being. They also help families understand and cope with the behavioural and cognitive changes of their loved one. Psychiatrists work closely with neurologists to coordinate care, ensuring medications are used safely and manage psychiatric symptoms effectively. Supporting mental health is essential, as caring for the mind helps the whole person cope better.

Genetic counselling

CARASIL can easily be mistaken for other neurological conditions, such as multiple sclerosis, which is why clear communication between doctors is so important.⁴ Because CARASIL is rare, it may take time for someone to be referred to the right specialist. Brain scans can also look similar to those seen in other conditions, so the only reliable way to confirm CARASIL is through genetic testing, which identifies mutations in the HTRA1 gene.⁵ For this reason, early referral and coordination between neurologists, geneticists, and other specialists can help avoid unnecessary medical procedures, ensuring patients receive the right care as soon as possible.

Future directions

A nerve-signalling pathway in the brain (TGF-β) has been identified as a key mechanism in CARASIL. ² The pathway becomes overactive, damaging small blood vessels. This has led researchers to suggest that treatments aimed at blocking or reducing this overactive signalling might help slow the cognitive decline in CARASIL. However, there is very little research on this so far, and these approaches have not yet been explored in depth.

Living with CARASIL

Living with CARASIL can be challenging, but ongoing care and support can help people stay as comfortable and independent as possible. Although there is currently no specific treatment, management focuses on easing symptoms and improving quality of life. Staying active within safe limits, using walking aids, and attending physiotherapy can support mobility, while regular check-ups help specialists monitor changes in cognition and mental health. Counselling and patient support groups also provide valuable emotional support.

Summary

• CARASIL is a rare inherited disease that affects the brain, spine, and emotions, often beginning in early adulthood.
• There is no specific treatment, but a multidisciplinary team - neurologists, orthopaedic specialists, psychiatrists, physiotherapists, and genetic counselors can greatly improve symptom management and quality of life.
• Accurate and early diagnosis through genetic testing is essential, as CARASIL can be mistaken for other neurological conditions.
• Ongoing research into the HTRA1 gene and TGF-β signalling offers hope for future treatments.