What is White Matter Lesions?
The brain’s white matter makes up about half of our brain and acts like a network of cables. This network allows different parts of the brain to communicate with each other. The white matter lies beneath the brain’s gray matter and closer to the surface of our spinal cord. Interestingly, the white matter has evolved more than the gray matter over time.
The white matter is made up of nerve fibers, known as axons, that are either covered in a fatty insulation called myelin or they are not (myelinated or unmyelinated). These axons are supported by other types of cells, including those that produce myelin. The myelin is a key part of our nervous system’s functionality because it serves as insulation for the axons, allows signals to move rapidly along nerves, and protects nerves from injury. Nearly half of the myelin content is water while the rest is mainly made up of proteins and fats.
Damage to the white matter, referred to as white matter lesions or leukoaraiosis, can occur due to various brain disorders, including small vessel brain diseases and non-vascular conditions. These changes in the white matter can be detected using MRI scans, which are the best current method to investigate such lesions. When MRI scans show bright spots in the white matter, they are often referred to as white matter hyperintensities (WMHs). These are particularly clearly seen on certain types of MRI sequences. These lesions were first observed using brain CT scans in 1985.
White matter lesions are quite common in older individuals who don’t show any symptoms. They are commonly found in people with uncontrolled chronic high blood pressure. The amount of these lesions tends to increase as we age. Although they were initially seen as a normal part of aging, recent research has revealed that having a large amount of white matter lesions can be an indicator of an increased risk of serious conditions like stroke, cognitive decline, depression, and disability, and can even potentially lead to death.
Besides small vessel disease, white matter lesions can be caused by other conditions that lead to the loss of myelin, inflammatory disorders, and degenerative disorders. Depending on where and how the white matter damage spreads, it can lead to very different health issues. Therefore, this group of conditions and diseases includes a wide range of clinical situations regarding their cause, development, pathological features, clinical presentations, imaging, and treatment options.
What Causes White Matter Lesions?
White matter lesions are changes that occur in the brain. These changes can have many causes, and can be grouped into two categories: vascular (involving the blood vessels) and non-vascular (not involving the blood vessels).
Vascular Causes of White Matter Lesions
These are related to the blood vessels:
* Microvascular ischemic disease or small vessel disease- where the small blood vessels are damaged.
* Atherosclerosis- the hardening of the arteries, usually due to fat and cholesterol build-up
* Migraine- severe, recurring headaches
* Amyloid angiopathy- an abnormal build-up of proteins in the blood vessels in the brain
* Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy- a rare, inherited condition that damages blood vessels in the brain
* Vasculitis- inflammation of the blood vessels
* Susac syndrome- a rare disease that impacts the brain, retina, and inner ear
Non-Vascular Causes for White Matter Lesions
These aren’t related to blood vessels:
* Inflammatory Conditions: such as Multiple sclerosis, acute disseminated encephalomyelitis, and neuromyelitis optica
* Infectious Diseases: Such as those caused by HIV, the herpes simplex virus, syphilis, and Lyme disease, among others
* Toxic Causes: Such as chronic alcohol abuse, carbon monoxide poisoning, inhalation of harmful substances, and some drug-related conditions
* Metabolic Causes: Such as Vitamin B12 deficiency, copper deficiency, certain liver diseases, and thyroid conditions
* Tumors: Such as glial tumors and lymphoma in the central nervous system
* Traumatic Causes: Resulting from radiotherapy or concussion
Genetic causes can be involved as well. These include certain inherited metabolic diseases, disorders affecting the structures within cells known as peroxisomes and mitochondria, disorders related to abnormalities in the metabolism of amino acids and organic acids, and other genetic diseases where the cause is still unknown. Some examples are Vanishing white matter disease and myotonic dystrophy.
Additionally, we could distinguish white matter lesions as primary or secondary. Primary ones are when the cause is unknown, while secondary ones have known causes.
Risk Factors and Frequency for White Matter Lesions
The likelihood of developing white matter lesions, a type of damage that can occur in the brain due to aging, increases with age. Around 10% to 20% of people have these lesions by the time they’re 60, and almost everyone has them by the time they reach 90. There are certain conditions that affect these white matter areas more frequently, like multiple sclerosis, progressive multifocal leukoencephalopathy, and certain kinds of tumors. Also, some disorders affect white matter in children specifically, either from birth or acquired later.
- White matter lesions linked to aging reportedly affect 10% to 20% of people at age 60, and almost 100% of people over 90.
- This type of brain damage is common across different ethnic backgrounds, including Japanese, Chinese, Caucasian, African-American, and Caribbean Black populations.
- Multiple sclerosis, an inflammatory neurological condition, affects about 2,500,000 people worldwide. In the US, up to 140 cases occur per 100,000 people in northern states, with slightly lower rates in the south.
- The condition neuromyelitis optica spectrum disorder (NMOSD) is found in about 1 to 10 out of 100,000 people depending on race. It’s more common in Black populations.
- Progressive multifocal leukoencephalopathy (PML) develops in 1% to 4% of individuals suffering from AIDS. PML can also be a severe side effect of treatments that suppress the immune system, like organ transplants.
- Gliomas, a type of tumor, account for up to 35% of brain tumors in young adults and adolescents.
- White matter damage from hereditary disorders, or leukodystrophies, is seen in approximately 1 out of every 8000 live births.
- Acquired white matter disorders in children are less common, occurring in about 1.66 out of 100,000 children.
Signs and Symptoms of White Matter Lesions
White matter lesions in the brain can have varying effects on patients, depending on their cause or “etiology.” In some cases, it’s possible for these lesions not to cause any noticeable symptoms. However, when larger lesions become connected or “confluent”, older patients may experience subtle difficulties with daily tasks, memory problems, dementia, issues with urine control, problems with walking or balance, and even mental health disorders.
The location and spread of these lesions can also influence a patient’s clinical symptoms. For example, in a condition called small vessel disease, white matter lesions are usually observed in particular regions of the brain. This can lead to problems with cognition, coordination, vision loss, and dizziness, or cause severe headaches.
Patients with a condition known as multiple sclerosis (MS) often have lesions in the white matter of the brain. MS symptoms can range widely among patients and may include:
- Fatigue
- Blurred vision in one eye
- Changes in sensitivity
- Muscle abnormality
- Urinary incontinence
- Difficulty swallowing or speaking
- Pain
- Anxiety and depression
- Numbness and tingling
- Problems with cognition
The progression of MS can vary greatly among patients. Some people’s symptoms may get worse quickly, while others may go through periods of illness and recovery.
Another condition marked by white matter lesions in the brain is neuromyelitis optica spectrum disorder (NMOSD). This can lead to severe vision loss or weaken limbs due to nerve inflammation. NMOSD may also lead to sensations like extreme tiredness or narcolepsy, and even seizures. Much like MS, NMOSD typically has a cycle of relapses and recoveries.
In children, white matter lesions causing problems with development, cognition, and movement might point to a condition called leukodystrophy. However, if symptoms such as fever, headache, vomiting, confusion, or altered consciousness appear quickly, it might indicate acute disseminated encephalomyelitis. While migraines have been associated with structural changes in the brain’s white matter, these usually don’t cause additional neurological problems or increased risk of cognitive decline.
Testing for White Matter Lesions
If you have white spots on your brain scans – known as white matter lesions – your doctor will examine you based on your age, your symptoms, and how the lesions look on the MRI scan. These white spots could mean you have a condition affecting the small blood vessels in your brain, which is linked to other conditions like heart disease or stroke. To check for these, your doctor might ask for routine blood tests including a complete metabolic panel, lipid profile, and HbA1c, which measures your average blood sugar levels.
Your doctor might also measure the size and number of your white matter lesions to check how they change over time. They can use different scales, like the Fazekas scale, to help them do this.
If the doctor thinks your white matter lesions are not caused by problems with your blood vessels, they might need to do more tests to figure out what’s causing them. For example, they might look at your cerebrospinal fluid – the fluid in your brain and spinal cord – if they suspect conditions like multiple sclerosis, acute disseminated encephalomyelitis (a brief but widespread attack of inflammation in the brain and spinal cord), and certain types of infections. MR spectroscopy, another type of scan, can also help to figure out what’s causing your white matter lesions by examining different substances in your brain.
You might also need more blood tests to check for certain types of diseases that can cause blood vessel inflammation, or genetic tests if your doctor thinks you might have leukodystrophy, a group of disorders characterized by the progressive degeneration of the white matter of the brain. Clinic scenarios for leukodystrophy can happen in children with white matter lesions. Bright spots on MRI scans of the brain are common and do not necessarily mean you have a severe or progressive condition, so don’t stress – your doctor will order the appropriate tests.”;
Treatment Options for White Matter Lesions
In older people, lesions, or damaged areas, in the white matter of the brain usually point towards small vessel ischemic lesions, which are usually symptoms of a lack of blood flow to the brain. These lesions can lead to cognitive problems, such as issues with thinking, memory, and decision-making. If caught early and managed properly, it’s possible to prevent further damage by targeting all risk factors related to blood flow in the body.
If an MRI reveals white matter lesions in seniors, doctors typically advise on managing blood flow-related risk factors, including:
* Keeping blood pressure under strict control
* Strictly managing diabetes
* Improving issues with abnormal cholesterol or fat in the blood (dyslipidemia)
* Encouraging physical fitness
* Advising to quit smoking
* Limiting alcohol usage
* Taking medication to prevent blood platelets from sticking together and forming clots (antiplatelets).
Taking preventive measures against migraines with auras (migraines that come with warning signs like flashing lights) can also help lower the risk of white matter lesions. B vitamins have been found effective in lowering homocysteine levels (high levels of this substance can damage blood vessels) and can help manage patients with small vessel disease.
Managing non-blood vessel related white matter lesions is mainly based on the root cause of the damage. For instance, white matter lesions that occur due to flare-ups of multiple sclerosis (MS), an autoimmune disease that affects the nervous system, can be treated with steroids. However, patients need long-term medication to slow down or stop the progression of the disease.
For patients with ADEM, a rare auto-immune disease that damages the protective cover of nerve fibers, immunosuppression, which is usually done by administering high doses of glucocorticoids (steroids), is the preferred way to manage symptoms. Acyclovir, an antiviral drug, may also help in some cases.
Leukodystrophies, which are rare, progressive, metabolic, genetic diseases that affect the brain, spinal cord and often the peripheral nerves, do not have a specific treatment; the approach to care is only supportive and symptom management. Lastly. white matter lesions that are caused by specific ailments, such as progressive multifocal leukoencephalopathy (a rare and often fatal disease characterized by damage to the white matter), HIV, and gliomas (a tumor that starts in the glial cells of the brain or the spine), must receive treatment specified for those conditions.
What else can White Matter Lesions be?
Identifying the patterns of white matter lesions in MRI scans is very important because it can help diagnose many conditions.
When doctors see symmetrical (the same on both sides) white matter lesions, they consider several possibilities, based on where the changes are found:
- In both hemispheres of the brain: Conditions like toxic encephalopathy, HIV encephalopathy, autoimmune encephalopathies, and vitamin B12 deficiency
- Close to the ventricles (fluid-filled spaces in the brain): Possibilities include small vessel disease, HIV encephalopathy, vitamin B12 deficiency, metachromatic leukodystrophy, X-linked adrenoleukodystrophy, and disappearing white matter disease
- In the subcortical region, including arcuate fibers: Conditions like Alexander disease, Kearns-Sayre syndrome, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
- In the frontal (front) part of the brain: Diseases such as Alexander disease and metachromatic leukodystrophy could be the cause
- In the parietal/temporal/occipital lobes: Conditions like posterior reversible encephalopathy, heroin abuse, and Krabbe disease
- In the corpus callosum (the part of the brain that connects the two hemispheres): Conditions like Marchifava-Bignami disease, metachromatic leukodystrophy, and Krabbe disease
- In the cerebellum (at the back of the brain): Conditions like toxic encephalopathy and mitochondriopathies
If the affected area is mainly in the central pons (a part of the brain), it could potentially be central pontine myelinolysis.
When the white matter changes are asymmetrical (different on both sides), the potential diagnoses include:
- Patchy multifocal confluent lesion: Conditions like multiple sclerosis, autoimmune encephalopathies, and CADASIL
- In the parieto-occipital regions: progressive multifocal leukoencephalopathy (PML)
What to expect with White Matter Lesions
The outlook for people with white matter lesions, which are abnormal areas in the brain’s white matter, can vary greatly and depends on what caused these lesions. If they’re due to aging, these lesions are generally permanent and can get worse over time. Bigger, widespread white matter lesions tend to have a negative outlook as they often lead to cognitive impairment, which affects brain functions like memory and thinking and can cause a significant decline in overall functionality.
White matter lesions that result from multiple sclerosis (MS) can have different outcomes for different patients. Severe disabilities occur in 5% of patients within the first five years from disease onset, while between 10% to 20% of MS patients stay unaffected without therapy after 20 years.
Neuromyelitis optica (NMO) and acute disseminated encephalomyelitis (ADEM) have varying outcomes. They can either result in full recovery or lead to long-term physical disability, especially in ADEM cases that follow measles.
The outlook for acute demyelinating disease, a sudden attack on the protective covering of nerve fibers, depends on the severity of the initial illness. Patients who respond well to treatment usually have a good outlook.
However, leukodystrophies, a group of rare genetic disorders that affect the nerves, brain, spinal cord, and often muscles, usually have a poor prognosis. On the other hand, reversible causes like metabolic and toxic encephalopathies, which refer to brain disease, damage, or malfunction caused by harmful substances or metabolic issues, typically have a good prognosis.
Possible Complications When Diagnosed with White Matter Lesions
Severe damage to the white matter in the brain can lead to a range of health issues. These issues may include cognitive (thinking, understanding, learning, remembering) impairment, an overall decline in one’s ability to function, stroke, mood disorders, and problems with walking and balance. Damage to the white matter can also cause shrinkage in the grey matter of the brain and quicker deterioration of nerve cells.
Moreover, diseases not related to blood vessels, like Multiple Sclerosis (MS), Acute Disseminated Encephalomyelitis (ADEM), and Neuromyelitis Optica (NMO), can cause significant white matter damage, leading to disability.
Effects of Severe White Matter Damage:
- Cognitive impairment
- Global functional decline
- Stroke
- Mood disorders
- Walking and balance problems
- Grey matter shrinkage in the brain
- Quick nerve cell deterioration
- Disability due to diseases like MS, ADEM, and NMO
Preventing White Matter Lesions
It’s important to spot people with risk factors for blood vessel diseases early and guide them about changes in their lifestyle and ways to manage other health conditions they may have. Keeping an eye on their own blood pressure and blood sugar levels, making changes to their diet, losing weight, and boosting physical fitness can decrease the development of white matter lesions. White matter lesions are alterations in the brain tissue that can occur for various reasons, such as aging or diseases.
Involving themselves in challenging leisure activities that encourage thinking can help improve their “cognitive reserve”. The term cognitive reserve is used to describe the brain’s ability to improvise and find alternate ways of getting a job done. This can offer protection to their mental function, and keep late-life melancholy away in patients living with white matter lesions.
