What Is White Matter Disease?

A variety of neurological conditions cause it

Medically reviewed by Brigid Dwyer, MD

White matter disease is a group of conditions that specifically affect the areas of the central nervous system (CNS) defined as white matter. Some of these conditions, such as multiple sclerosis (MS), affect only the white matter of the CNS (brain and spinal cord), and some conditions, such as vascular dementia, may also affect other areas of the brain.

White matter diseases can cause a range of neurological symptoms, including weakness, sensory loss, or vision changes, and they can also cause nonspecific symptoms (symptoms that can be caused by other conditions as well), such as fatigue and difficulty concentrating. This article describes the types of white matter diseases, their symptoms, causes, diagnosis, treatments, and prognosis.

What Is White Matter?

The white matter of the CNS appears white when viewed microscopically after preparation with some stains. White matter is heavily myelinated, meaning it is enclosed in a myelin sheath. Myelin is a type of fatty protective coating over the nerves that helps to facilitate the speed of nerve signals in nerve pathways throughout the nervous system.

White matter is located in the deep, inner regions of the brain and the outer regions of the spinal cord.

By contrast, the gray matter appears gray when viewed microscopically after some types of staining. Gray matter is located on the outer regions of the brain and the central areas of the spinal cord.

Types of White Matter Disease

There are many different white matter diseases. They can be caused by inflammation, vascular disease, medication, or infection and may include:

• Multiple sclerosis: This inflammatory demyelinating neurological condition affects the white matter of the brain and spinal cord. It causes exacerbation and remissions, meaning episodes of worsening with moderate levels of improvement between episodes.

• Vascular dementia: This progressive type of dementia occurs due to an accumulation of white matter damage in the brain due to strokes. The symptoms can develop with a gradual progression, but sometimes the effects can worsen suddenly after a stroke.

• Acute disseminated encephalomyelitis (ADEM): This severe inflammatory condition can affect the white matter of the brain and the spinal cord. An infection often precedes it. However, sometimes there is no clear trigger for an episode of ADEM.

• Human immunodeficiency virus (HIV) encephalopathy: In late stages of HIV infection, white matter disease may develop in the brain. Sometimes this is associated with viral infections or medication, and sometimes there is no clear trigger.

• Progressive multifocal leukoencephalopathy (PML): This rare, severe, inflammatory brain condition can occur in association with the reactivation of the very common John Cunningham (JC) virus. This reactivation and corresponding inflammatory response can occur due to immune deficiency caused by HIV infection, chemotherapy, or immunosuppressants used for the treatment of MS or other inflammatory disorders.

• Metabolic myelinolysis: This rare condition occurs as a result of toxic damage to the white matter that may develop in response to rapid and extreme changes of electrolyte concentration in the body, particularly sodium.

Some of the conditions that cause white matter disease do not involve other areas of the CNS. However, many white matter diseases have the potential to affect other areas of the CNS in addition to white matter and may manifest as white matter disease or as more extensive CNS disorders.

White Matter Disease Symptoms

The symptoms of white matter disease can be either permanent or intermittent, depending on the disease. The symptoms corresponded to the affected areas of CNS involvement.

Many nerve pathways travel throughout the white matter in the CNS. So, relatively small areas of white matter disease can cause substantial weakness or sensory changes. Extensive white matter disease can also cause nonspecific symptoms, such as dementia and vision changes.

Symptoms of white matter disease may include combinations of the following:

• Diminished vision

• Double vision or blurred vision

• Nystagmus (jerking eye movements)

• Weakness, especially on one side of the body

• Sensory loss or diminished sensation, especially on one side of the body

• Impaired coordination

• Difficulties with memory, decision, making, or concentration

• Fatigue

Most white matter diseases do not cause all of these symptoms. Rather, they each produce a pattern of symptoms that are characteristic of that particular disease.

Causes

White matter disease can occur due to degeneration, demyelination, inflammation, infection, drug toxicity, nutritional deficiency, or any condition that causes damage to the white matter of the CNS.

Many of the conditions affecting white matter are associated with inflammation. In fact, vascular dementia, which occurs due to strokes, is associated with extensive vascular disease affecting the small blood vessels of the brain. Risk factors include smoking, uncontrolled high blood pressure (hypertension), unhealthy fat and cholesterol levels, and untreated diabetes—all of which contribute to inflammation of the blood vessels.

Diagnosis

White matter disease is diagnosed through a process that involves taking a medical history, performing a physical examination, and reviewing imaging tests blood samples or samples of cerebrospinal fluid (CSF).

The key features of the medical history include a description and timing of the symptoms, and any other associated symptoms, such as a fever.

The physical examination helps determine whether the condition is mainly a neurological condition or a systemic disease (one that affects the entire body). Your medical provider will examine the appearance of your skin, ask you to identify painful areas, check for weakness or sensory changes, and check reflexes and coordination.

Diagnostic testing may include:

• Imaging tests: Often, imaging of the brain or spinal cord is part of evaluating white matter disease. The area that is imaged is determined based on the physical examination and symptoms. Brain or spinal cord magnetic resonance imaging (MRI) or computed tomography (CT) are the tests of choice in evaluating white matter disease.

• Blood tests: Blood samples can sometimes help identify the underlying cause of white matter disease. These tests may detect evidence of an infection or inflammation.

• Lumbar puncture (LP): An LP, sometimes called a spinal tap, is used to obtain a sample of CSF, which is tested for changes in proteins, inflammatory markers, or evidence of infection.

Treatment

Some white matter diseases can be reversed or controlled with treatment. However, some white matter diseases can only be treated symptomatically.

Immune suppression: Several different white matter diseases can be treated with anti-inflammatory medications, such as steroids, immunoglobulins, or plasmapheresis (removing blood plasma). These treatments are used for MS exacerbations and ADEM. While they are sometimes used to manage acute stages of HIV encephalopathy or PML, the underlying infections can worsen with immunosuppression.

Additionally, MS is also treated with disease-modifying therapy (DMT), which helps prevent exacerbations.

Vascular dementia is caused by an accumulation of small-vessel strokes that cause extensive white matter damage. The white matter damage can’t be treated, but sometimes additional damage can be prevented with treatment, such as blood thinners and control of blood pressure and blood glucose (blood sugar).

Prognosis

The prognosis of white matter disease varies. MS is not a fatal disease. By managing the MS and co-occurring conditions, life expectancy may be only slightly shorter.

Most infectious causes of white matter disease can be treated with medication, resulting in improvement and good survival. However, HIV encephalopathy and PML are associated with a very poor prognosis and short life expectancy.

Vascular dementia generally is associated with a reduced life expectancy after diagnosis. This is because vascular dementia develops due to factors that can also increase the risk of stroke and heart disease.

Summary

White matter diseases affect the white matter in the CNS. Some white matter diseases only involve white matter, such as MS. Some white matter diseases can also involve other parts of the CNS.

There’s a wide range of white matter diseases. The timing, causes, symptoms, and treatments vary. Most of these diseases are associated with inflammation, but there are also other underlying causes with each of these conditions. Some white matter diseases can be treated effectively, but others are permanent, such as vascular dementia.