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What Is White Matter Disease Of The Brain

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Understanding White Matter & White Matter Disease

Mapping the white matter of the human brain

What is white matter?

The brain is made up of neurons and glia . The neurons have cell bodies and also have long arms, called axons, that function like wires to send signals to other nerve cells or organs.

To work properly these axons need to be insulated, akin to an electric wire, by being covered in a special substance called myelin – which is provided by glial cells.

The neuron cell bodies tend to cluster in certain areas of the brain along the outer edge and in other structures centrally, while the axons run like wires between different parts of the brain centrally. When the brain is examined, the cells bodies tend to have a grayish appearance and the myelin appears whitish, hence the terms gray matter and white matter.

Why is white matter important?

Myelin, the material encasing nerve axons that makes white matter white, acts as an insulator allowing nerve signals to jump along the axon of a nerve at greater speed and distances. To put it in more simple terms, regions of the brain need to communicate in order to carry out behavior – white mater is what supports these vital connections, ensuring the smooth operation of our nervous system.

Disruption of the white matter leads to dysfunction in this signaling ability and within the neurons themselves. Loss of normally formed white matter is known as demyelination. Problems with forming the white matter properly are known as dysmyelination.

What diseases affect white matter?

Cognition And White Matter Aging

Cognitive aging is a selective process that is marked by significant declines on tasks for which successful performance demands substantial mental effort, rely heavily on processing speed, and are characterized by complexity and novelty of the stimuli. On the other hand, performance on tasks that depend on semantic knowledge and/or overlearned skills is relatively preserved .

Correlations between regional brain volumes and cognitive abilities tend to be modest however, the strength of these relationships increases with advancing age suggesting that variability in neuromorphometry among older adults at least partially accounts for age-associated variability in cognition. For example, we recently showed that relative frontal lobe white matter volume mediated the association between age and performance on tasks of memory and executive functions . Furthermore, using a multivariate approach, the degree to which older adults manifested a pattern of age-associated density loss was associated with poorer performance on tasks of memory and executive abilities .

Why Do Westudy It

A large number of peopleliving with dementia will have Alzheimers disease and white matter disease atthe same time. Understanding the white matter disease component of theirdementia might lead to improved or specific treatments. This is because white matterdisease is in part linked to common problems with the heart and blood vessels causedby smoking, diabetes, high blood pressure and high cholesterol. These arethings we can prevent or treat.

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What Is White Matter Disease

White matter disease is an illness that influences the nerves that connect different pieces of the mind to one another and to the spinal line. These nerves are likewise called white matter. White matter disease makes these regions decrease in their usefulness. This infection is additionally alluded to as leukoaraiosis.

An individual with white matter sickness will bit by bit have expanding trouble with the capacity to think. Theyll likewise have dynamically demolishing issues with balance.

White matter disease in the brain is an age-related, reformist disease. Age-related implies that it normally influences more established individuals. Reformist implies that it deteriorates over the long haul. The future after a conclusion of white matter infection relies upon the speed it advances and the seriousness of some other conditions it might cause, similar to stroke and dementia.

White matter disease is accepted to be a factor in the two strokes and dementia. Notwithstanding, more examination should be accomplished for additional affirmation.

What Iswhite Matter Disease

White matter diseases

Within the Dementia Research Centre, a team of researchersfocus on understanding how disease of the brains white matter is related to ageingand dementia.

White matter is a structured network of cells which act likecables to link up communicating brain regions. This linkage of different brainregions enables high level processes such as thought, movement anddecision-making to occur. During ageing these cells can become disorganised,diseased and dysfunctional.

The brain images here show white ‘blobs’ that are characteristic of white matter disease. These blobs are common in people with heart disease or problems with blood vessels and might be present with or without any cognitive issues.

White matter abnormalities can lead to disruption of brain circuits andcontribute to cognitive symptoms similar to those caused by Alzheimers disease.

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Association With Stroke Severity And Post

Severity of leukoaraiosis has been linked to poor functional post-stroke outcome in both short- and long-term follow-up studies. In patients with acute ischemic stroke, severity of WMH is significantly associated with poor functional outcome at 3 months and beyond. When the topography of WML is considered, PVH burden, but not subcortical or deep WMH, appears to be linked to unfavorable clinical outcome in both short- and long-term studies. A study in patients with spontaneous ICH also showed that higher leukoaraiosis burden was an independent marker of worse functional outcome. [

Besides being a predictor of functional outcome after stroke, severity of leukoaraiosis was independently associated with larger infarct cores , greater infarct volume growth , and increased risk of hemorrhagic transformation and parenchymal hematoma following intra-arterial thrombectomy for treatment of acute ischemic stroke, especially leukoaraiosis in deep white matter region. [

Wanted: A Behavioral Neurology Of White Matter

The study of higher functions in humans requires consideration of all the brains neural tissues. Long neglected as a contributor to the organization of cognitive and emotional operations, white matter is the object of intense, intriguing, and increasingly fruitful efforts to improve our understanding. Studying people with white matter disorders to correlate their brain lesions with specic behavior changes promises a wealth of insights. Increasingly, this method will be complemented by sophisticated neuroimaging techniques that yield detailed visualization of white matter tracts as they participate in the cognitive and emotional operations of distributed neural networks.

In practical terms, an appreciation of the brain-behavioral importance of white matter disorders can greatly benet patients, especially as early recognition and treatment often determine an outcome. In theoretical terms, further study of white matter and its disorders expands our knowledge of the brain as an extraordinarily complex structure in which the connectivity provided by white matter is central to cognition, emotion, and consciousness itself.

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Advancing Care For Children With White Matter Disease: Leukodystrophy Center

Leukodystrophies are inherited disorders of the white matter of the brain and spinal cord that can cause problems with movement, speaking, vision, hearing, and overall development. These disorders are difficult to recognize and diagnose. The Leukodystrophy Center at Children’s Hospital of Philadelphia provides comprehensive clinical care, diagnostic testing and the most advanced treatments available to infants, children and adolescents living with these inherited white matter diseases. In this video, hear from clinicians and patient families who have been cared for by CHOPs Leukodystrophy Center, and learn how the team is using cutting-edge research to better understand the causes of leukodystrophy and advance clinical care.

Ischemic Demyelination And Ischemic Stroke Risk

The Basics: White Matter Disease | WebMD

Patients with ischemic white matter disease are at enhanced risk for stroke . In addition, white matter hyperintensities on MRI in elderly normal volunteers correlate with subtle cognitive deficit with reduced speed of complex mental processing . Lacunar-type stroke has been reported to have a recurrence rate of up to 12% per year, and one can hypothesize that asymptomatic small vessel disease is presumably associated with at least some heightened risk when compared with an age-matched population without evidence of ischemic demyelination on brain scan. Multiple studies indicate that it is the confluence of the ischemic white matter lesions on MRI brain scan that is associated with the greatest risk for clinically evident ischemic stroke . This confluence of larger white matter abnormalities correlates with the changes described as leukoaraiosis on CT brain scan.

Roger E. Kelley, Brian P. Kelley, in, 2018

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White Matter Consists Mainly Of Nerve Fibers

White matter appears white because the protective wrapping around nerve fibers, or axons, is a pale, fatty tissue called myelin.

Axons are like the electric wires of the brain, says Rhonda Voskuhl, MD, professor of neurology at the UCLA Brain Research Institute and director of the UCLA Multiple Sclerosis Program in Los Angeles.

In MS, the immune system attacks the myelin in the brain, spinal cord, and optic nerves. The attack causes inflammation that eventually leads to sclerosis, which is the medical term for scarring.

When MS attacks these parts of the brain, its like stripping the rubber off the wires. That slows down conduction speed and causes the types of MS symptoms that come and go, says Dr. Voskuhl. An attack may last for weeks or months, but then the inflammation cools off, and the area recovers completely or partially.

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Phases Of White Matter Disease

Various sorts of white matter disease may have various stages. For instance, there are a couple of kinds of MS, and each contrasts by the way it advances.

As of now, there is no widespread arranging framework for the different types of white matter infection.

All things considered, a few scientists have proposed an organizing system for white matter sores, which they recommend would help medical services experts characterize individuals into phases of white matter disease.

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Can It Be Prevented

Age-related white matter disease is progressive, meaning it can get worse. But you can take steps to stop it from spreading. Scientists think you might even be able to repair the damage, if you catch it early.

Keep your blood pressure and blood sugar in check. That can lead to white matter changes. To keep your heart healthy, follow a low-fat, low-salt diet, and get about 2 and a half hours of moderate-intensity exercise each week. Manage diabetes if you have it and keep your cholesterol in check. If you smoke, stop now.

American Physical Therapy Association, Section on Neurology: “White Matter Disease.”

Filley, C.M. Therapeutic Advances in Neurological Disorders, September 2012.

HOPES Stanford University: “White Matter and HD.”

The Dana Foundation: “Why the White Brain Matters.”

Vasquez, B.P. Journal of Neuropsychology, Feb. 24, 2014.

Xiong, Y.Y. Journal of Aging Research, published online Aug. 23, 2011.

Raz, N. Biochemica et Biophysica Acta Molecular Basis of Disease, March 2012.

Yang, D.W. Alzheimer’s & Dementia, July 2010.

Schmahmann, J.D. Annals of the New York Academy of Sciences. October 2008.

UC Davis Health System: “White Matter Matters.”

American Heart Association: “How to Prevent Heart Disease at Any Age.”

Acute Isolation Of Microglia From Adult Mouse Brain

Understanding White Matter Disease

Animals were sacrificed by means of saline perfusion under inhalation anesthesia with 4% isoflurane in oxygen. The brains were isolated and kept in ice-cold dissection solution . For the isolation of microglia from white and gray matter regions, the forebrain and cerebellum were cut into approximately 1.5 mm thick coronal sections. Dissection was performed under magnifying glass with the tissue wet with medium A. Corpus callosum, cerebellar white matter were pooled from 2 to 3 animals of a particular age group and considered as one sample from that age group. From the collected tissue, microglia were isolated at high purity using a discontinuous Percoll gradient . All steps of the isolation and staining procedure were performed at 4°C. Briefly, the tissue was transferred to a tissue homogenizer , and mechanically dissociated. The brain homogenate was then filtered through a 70 m cell strainer, washed with medium A, and pelleted by centrifugation . The density gradient separation was done using Percoll solutions with different densities . To obtain a stock isotonic Percoll solution , nine volume parts of Percoll were mixed with one volume part of 10x HBSS. Percoll solutions with the appropriate concentration were prepared via dilution of 100% Percoll with 1x PBS.

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Causes And Risk Factors

The cause of microvascular ischemic disease isnt completely understood. It can be the result of plaque buildup and hardening that damages the small blood vessels nourishing the brain. This is the same process that narrows and damages blood vessels to the heart and can lead to heart attacks.

Damage can block blood flow through the blood vessels in the brain, depriving brain cells of oxygen. Or, it can cause blood vessels in the brain to leak and bleed, which can damage neighboring neurons.

Risk factors for microvascular ischemic disease include:

  • high blood pressure

Risk Of Stroke In High Risk Populations

Many prospective studies evaluated WMH and risk of stroke in high risk populations. A study in 89 Japanese participants who had clinical lacunar infarction and followed up for a mean of 51 months found that extensive WMH at baseline was a significant predictor of stroke risk A study in 121 American patients with lobar ICH showed that CT-based evidence of white matter damage nearly quadrupled the risk of recurrent ICH after 2.7 years of follow-up. A study of 81 Swedish patients with lacunar infarction found that severity of WML was a predictor of recurrent stroke , when followed long-term . Similarly, extensive WML was associated with recurrent stroke in a study of 228 Chinese patients with stroke . The Amsterdam Vascular Medicine Group in the Netherlands reported that patients with confirmed atherosclerotic disease including recent myocardial infarction , ischemic stroke , or peripheral arterial disease and evidence of PVH on neuroimaging have a higher recurrent ischemic stroke rate at 3.5 years compared to those without PVH . A study in 266 Japanese patients with ischemic stroke or ICH found that those patients with advanced WMH but no microbleeds developed had the highest recurrence rate of ischemic stroke among 3 other patient subgroups . [

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Incident Dementia And Cognitive Decline

White matter hyperintensities were associated with an increased risk of dementia in the general population, but not in studies on high risk populations . When subtypes of dementia were assessed, the three studies that investigated the relation of white matter hyperintensities with incident vascular dementia found a significant association, both in the general population and in patients with mild cognitive impairment.313341 Conversely, although the meta-analysis testing the relation of white matter hyperintensities with incident Alzheimers disease yielded an overall significant association, this association was driven by the large population based study,31 whereas the two smaller studies on patients with mild cognitive impairment did not identify any association.4149 Finally, our systematic review suggests that, in most studies looking at the association of white matter hyperintensities with decline in cognitive performance, white matter hyperintensities were associated with a faster decline in global cognitive performance as well as in executive function and processing speed. This was true both in the general population and in high risk patients with mild cognitive impairment, memory problem, or cerebrovascular disease.

What Causes Cerebral Small Vessel Disease

White Matter Affects Alzheimer’s Treatment

This is a topic of intense research, and the experts in this area tend to really nerd out when discussing it. One reason its difficult to give an exact answer is that cerebral SVD is a broad umbrella term that encompasses many different types of problems with the brains small blood vessels.

Still, certain risk factors for developing cerebral SVD have been identified. Many overlap with risk factors for stroke. They include:

  • Hypertension
  • Age

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What Is Cerebral Small Vessel Disease

Cerebral small vessel disease is an umbrella term covering a variety of abnormalities related to small blood vessels in the brain. Because most brain tissue appears white on MRIs, these abnormalities were historically referred to as white matter changes.

Per a recent medical review article, specific examples of cerebral SVD include lacunar infarcts , white matter hyperintensities , and cerebral microbleeds .

In many cases, cerebral SVD seems to be a consequence of atherosclerosis affecting the smaller blood vessels that nourish brain tissue. Just as ones larger blood vessels in the heart or elsewhere can accumulate plaque, inflammation, and chronic damage over the years, so can the smaller blood vessels.

Such chronic damage can lead the small blood vessels in the brain to become blocked , or to leak .

When little bits of brain get damaged in these ways, they can change appearance on radiological scans. So when an MRI report says white matter changes, this means the radiologist is seeing signs that probably indicate cerebral SVD.

Such signs of SVD may be described as mild, moderate, or severe/extensive, depending on how widespread they are.

Here is an enlargement of a good image, from the BMJ article Changes in white matter as determinant of global functional decline in older independent outpatients.

White Matter In The Brain

Think of the brain as a computer system, and it might be easier to understand. According to the UC Davis Health System, the gray matter of our brain is the computer and the white matter is the cables that connect everything together and transmit signals.

Want more of a biological explanation? White matter is tissue in the brain composed of nerve fibers. The fibers connect nerve cells and are covered by myelin . The myelin is what gives white matter its white color.

Myelin speeds up the signals between the cells, enabling the brain cells to quickly send and receive messages. It also provides insulation for the fibers, preventing the brain from short-circuiting.

White matter makes up about half of the brain, with gray matter making up the other half.

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