In their article, "Gray matter involvement in multiple sclerosis,"Dr. Istvan Pirko and his coauthors review recent informationabout multiple sclerosis (MS) (Neurology 2007;68:634–642).Most research focuses on how MS affects the myelin—a substancethat coats the nerves and is mainly made of fat. The authorsof this article describe what MS does to the nerve cell bodies(gray matter, see below) of the brain. Although research isalways going on in this area, there is more research to showthat involvement of the gray matter predicts the injury thatcan occur in MS.
Brain cells are called neurons. Neurons are made up of a cellbody. In the brain (and spinal cord), the cell bodies are groupedtogether in organized ways. When looking at the brain with thenaked eye, these groups of cell bodies have a grayish color,and so they are called gray matter.
The outer layer of the brain is one area where cell bodies aregrouped together; this region of gray matter is called the cerebralcortex. Deeper in the brain are other groups of cell bodies.These are also called gray matter but they are separate fromthe cerebral cortex and are called nuclei. The two areas ofgray matter are connected together in many ways. The connectionsbetween these areas allow us to speak and think.
Nerve cells talk to each other using electrical and chemicalsignals. These signals must be sent very fast. In order forthis to occur, cells must be connected by "wires." These wiresare like long threads that extend from the nerve cell body.These threads are called axons. Some axons are short and travelfrom one part of the brain to another. Others are very long,and travel from the brain to the spinal cord. Some nerve cellsare several meters long.
Electrical signals travel much faster through wires that arecoated or insulated. This prevents them from short-circuiting.Axons are coated with a substance called myelin which allowsfor fast movement of signals from one area of the brain to another,or from one part of the body to another. Like gray matter, axonsare also grouped together. Because myelin appears white to thenaked eye, parts of the brain or spinal cord that are made upof axons are called white matter.
Experts are able to carefully study the living brain by takingpictures of the brain by using MRI. These methods are alwaysgetting better so clearer pictures can be taken and now expertscan see shrinking that occurs in the gray matter. Newer MRIscan look at brain function and brain structure. Magnetic resonancespectroscopy (MRS) is another process that experts use to seecertain proteins in the brain. One protein is called N-acetylaspartate(NAA). NAA occurs only in nerve cells. In people with MS, theamount of NAA is reduced. Reduced NAA means neuronal loss andshrinking. In other words, scientists can use MRS to show whathappens to gray matter in people with MS.
Functional MRI (fMRI) is a new technology that can measure specificbrain functions. During this test, a person performs a specifictask like reading. fMRI shows the areas of brain that are activewhile reading. In a normal person, several areas would lightup on fMRI. fMRI in a person with MS shows that fewer areaslight up. In other words, fMRI highlights where MS affects thatgray matter.
Thinking occurs in the gray matter. A disease that changes graymatter can harm thinking, memory, and judgment. Some studiesshow that gray matter shrinking leads to problems with thinking.Many people with MS say that they have poor memory or troublethinking clearly. MS causes gray matter problems more oftenin the gradually progressive form of MS. People who have thisform are more likely to have permanent disability. Seeing shrinkingor atrophy on MRI means that there is some disability.
The cause of MS is still not clear. A better understanding ofhow MS affects the brain and spinal cord may provide this answer.Newer studies look at the living brain using new methods. Incombination with studies that look at the brain through a microscope,we may be able to find the cause of MS. Only by understandingthe cause can we develop a cure.
MS is a disease of the CNS (the brain and spinal cord). It affectswomen about twice as often as men. It usually starts at age30.
The cause of MS is unknown. However, there are several cluesabout how MS begins. For instance, MS occurs more often in peoplewho live in northern areas. Some experts believe that northernershad a bacteria or virus when they were children. The immunesystem—cells and organs in our bodies that fight infections—formsantibodies to the bacteria or virus.
Later in life, for reasons that are not known, the antibodiesattach to a protein in the myelin coating of the axons. Thebody becomes confused, and begins destroying the much-neededmyelin. Without myelin, nerve cell signals travel much moreslowly. This results in weakness, numbness, and other symptoms.
Something in our genes may be responsible for MS. For instance,MS is more likely to occur in first-degree relatives (mom, dad,brother, or sister) than in distant relatives or unrelated individuals.Twenty-five percent of identical twins, who have identical geneticmakeup, develop MS. In compari-son, only 2% of fraternal twins,whose genetic makeup is like a brother or sister, develop MS.
The genetic research in MS focuses on how our bodies are ableto recognize unfamiliar things. For instance, if someone receivesa liver transplant, the immune system may see the new liveras foreign and reject it. Research into the genetics of MS mayshow how some people’s bodies become confused. This wouldhelp experts figure out who may develop MS, where the body attacksits own myelin.
Most people think MS is an illness that mostly affects whitematter. Studies show that MS affects gray matter as well. WhenMS affects gray matter, the nerve cells die. Nerve cell deathcauses a decrease in the volume of the gray matter. A reductionin volume is called atrophy. Years ago, before MRI, an autopsymight show atrophy. Today, MRI can identify atrophy in the livingbrain. Newer MRIs are able to detect subtle changes even moreeasily.
If MS primarily affects the white matter, why do nerve cellsdie? Some scientists believe that an attack on myelin also affectsthe axon. Some nerve cells cannot live without their axons.When a nerve cell dies due to axonal injury, it is called Walleriandegeneration.
Some experts think that MS affects the nerve cell body directly.In other words, the nerve cell body is destroyed first. Whichis correct? Is it the axon first, or is an attack on the cellbody the beginning of what we call MS? The answer to this questioncould lead to a cure of this illness.
There are several types of MS. In one, the symptoms come andgo. In between the symptoms, the person may feel fine. Thistype of MS is called relapsing-remitting MS. The other maintype is called progressive MS. This type slowly worsens, resultingin a gradual loss of neurologic function. Some have observedthat white matter is more involved in the relapsing-remittingtype, while gray matter may be more involved in the graduallyprogressive form.
Are they separate illnesses? Do they overlap? The answers tothese questions remain unclear. More research into this complexarea is needed.
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Imaging and the brain
