Muscular & Cerebral Atrophy

Atrophy is the progressive degeneration or shrinkage of muscle or nerve tissue. In multiple sclerosis (MS), two types of atrophy are common: muscle atrophy (due to disuse of specific muscles) and brain or cerebral atrophy (due to demyelination and destruction of nerve cells).

When a person complains of muscle weakness, the doctor checks muscles for bulk and texture and for tenderness. Muscles are also checked for twitches and involuntary movements, which may indicate a nerve disease rather than a muscle disease. Doctors look for wasting away of muscle (atrophy), which can result from damage to the muscle or its nerves or from lack of use (disuse atrophy), as sometimes occurs with prolonged bed rest. Doctors also look for muscle enlargement (hypertrophy), which normally occurs with an exercise such as weight lifting. However, when a person is ill, hypertrophy may result from one muscle working harder to compensate for the weakness of another.

Cerebral atrophy is a common feature of many of the diseases that affect the brain. Atrophy of any tissue means loss of cells. In brain tissue, atrophy describes a loss of neurons and the connections between them. Atrophy can be generalized, which means that all of the brain has shrunk or it can be focal, affecting only a limited area of the brain. The result of this type of atrophy can be a decrease of function in the affected area of the brain. If the cerebral hemispheres are affected, conscious thought and voluntary processes may be impaired.

Cerebral Atrophy Symptoms:

Dementia

This is characterized by a progressive impairment of memory and intellectual function that is severe enough to interfere with social and work skills. Memory, orientation, abstraction, ability to learn, visual-spatial perception, and higher executive functions such as planning, organizing, and sequencing may also be impaired.

Seizures

These can take different forms, appearing as disorientation, repetitive movements, loss of consciousness, or convulsions.

Aphasias

A group of disorders characterized by disturbances in speaking and understanding language. Receptive aphasia causes impaired comprehension. Expressive aphasia is reflected in odd choices of words, the use of partial phrases, disjointed clauses, and incomplete sentences.

Muscular Atrophy

Muscle atrophy is the wasting or loss of muscle tissue. There are two types of muscle atrophy: disuse and neurogenic.

The first type of muscle atrophy is disuse atrophy and occurs from a lack of physical exercise. In most people, muscle atrophy is caused by not using the muscles enough. Those with sedentary jobs, medical conditions that limit their movement, or decreased activity levels can lose muscle tone and develop atrophy. Those who are bedridden can have significant muscle wasting. This type of atrophy can usually be reversed through exercise and/or better nutrition.

The second and most severe type of muscle atrophy is neurogenic atrophy. This occurs when there's an injury to, or disease of a nerve such as with MS. This type of muscle atrophy tends to occur more suddenly than disuse atrophy. This type of atrophy can't usually be reversed since there is actual physical damage to the nerve. Neuromuscular Electrical Stimulation (NMES) has been used as a form of physical therapy that applies electrical muscle stimulation via small electrical impulses to nerves and muscles in an effort to cause involuntary muscle contractions. The electrical impulses are sent by electrodes placed on your skin over the muscle or muscles.

Although people can adapt to muscle atrophy, even minor muscle atrophy causes some loss of movement or strength. Symptoms of muscle atrophy may include:

●	Balance problems, difficulty walking, and falls
●	Difficulty with speaking and swallowing
●	Facial weakness
●	Gradual memory loss
●	Impaired balance and coordination
●	Loss of muscle coordination
●	Numbness or tingling in arms or legs
●	Progressive loss of movement
●	Progressive weakness and numbness in the legs

Cerebral Atrophy

The loss of brain tissue, called brain atrophy, is a normal part of aging, but MS accelerates the process. Such atrophy is a critical indicator of physical and cognitive decline in MS, yet because measuring brain atrophy is expensive and complicated, it's done primarily in research settings.

The biological basis of gray matter atrophy in MS is not well understood, but gray matter damage seems to be the most critical factor leading to permanent disability. Until now, it was thought that the lesions or plaques observed in the white matter were the cause of the damage to the brain. New data indicates that these lesions account for only 30% of the atrophy in the gray matter; other unexplained neurodegenerative mechanisms are therefore also implicated.

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Principal Cause is Unknown

MS is a chronic inflammatory neurodegenerative disease of the central nervous system (CNS) that affects the brain and spinal cord. It's the most common chronic neurologic disease in young people and adults in Europe and affects approximately 2.5 million people throughout the world. The study was published in the journal Archives of Neurology (66(2):173-9) and was carried out by the team of Dr. Pablo Villoslada at the University of Navarre. Last December, these researchers joined Hospital Clínic, Barcelona-IDIBAPS. Until now, it was thought that the atrophy seen in the brains of patients with MS was caused by the plaque in the white matter. The new results show that these plaques explain only 30% of the lesions.

Until now it was assumed that MS predominantly affected myelin, a fat that sheaths the nerves. It was thought that the plaques that form in the myelin were directly responsible for the atrophy of the grey matter. This study was designed to determine whether the loss of volume–atrophy–in the brain’s structures was related to the presence of lesions or cuts in the nerves connected to them.

The researchers analyzed the brains of 81 people (61 with MS and 20 healthy people) using magnetic resonance imaging (MRI) and a morphometric method (volumetry). The study focused on the optical pathway, starting with the hypothesis that lesions in this part of the brain, and in no other, correlate with atrophy of the occipital cortex and the lateral geniculate nucleus (LGN), the main centers for processing visual information. The results indicate that the lesions in the white matter of the nerves originating in the LGN explain up to 28% of the variation in volume. Atrophy of the occipital cortex did not correspond to the presence of lesions in the optical pathway, probably because it is associated with many other pathways.

Thus, although the sclerotic plaques in the nerves contribute significantly to the atrophy of the grey matter, the remaining 72% must still be explained. The data suggest that other neurodegenerative processes are involved. Because atrophy of the grey matter is the main cause of the progressive form of the disease and its severe sequelae, it's important to gain a better understanding of the principal mechanism of the damage, apart from the classic plaques, in order to be able to apply this knowledge to treating the disease.

Cerebral Atrophy and Depression

A recent study reported on the UCLA Newsroom, looks at brain atrophy as a cause of depression for those with MS. Adding to all that ails people managing their MS is depression ― for which MS sufferers have a lifetime risk as high as 50%.

Yet despite its prevalence, the cause of this depression is not understood. It's not related to how severe one's MS is, and it can occur at any stage of the disease. That suggests it's not simply a psychological reaction that comes from dealing with the burden of a serious neurologic disorder.

Now, in the first such study in living humans, researchers at UCLA suggest a cause, and it's not psychological, but physical: atrophy of a specific region of the hippocampus, a critical part of the brain involved in mood and memory, among other functions.

Reporting in the early online edition of the journal Biological Psychiatry, senior study author Dr. Nancy Sicotte, a UCLA associate professor of neurology, Stefan Gold, lead author and a postdoctoral fellow in the UCLA Multiple Sclerosis Program, and colleagues used high-resolution magnetic resonance imaging (MRI) to identify three key sub-regions of the hippocampus that were found to be smaller in people with MS when compared with the brains of healthy individuals.

The researchers also found a relationship between this atrophy and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, a complex set of interactions among three glands. The HPA axis is part of the neuroendocrine system that controls reactions to stress and regulates many physiological processes. It's thought that this dysregulation may play a role in the atrophy of the hippocampus and the development of depression.

"Depression is one of the most common symptoms in patients with multiple sclerosis," Gold said. "It impacts cognitive function, quality of life, work performance and treatment compliance. Worst of all, it's also one of the strongest predictors of suicide."

The researchers examined three sub-regions of the hippocampus. They imaged 29 patients with relapsing-remitting MS (RRMS) and compared them with 20 healthy control subjects who did not have MS. They also measured participants' cortisol level three times a day; cortisol is a major stress hormone produced by the HPA axis that affects many tissues in the body, including the brain.

In addition to the difference between MS patients and healthy controls, the researchers found that the MS patients diagnosed with depression showed a smaller CA23DG sub-region of the hippocampus, along with excessive release of cortisol from the HPA axis.

"Interestingly, this idea of a link between excessive activity of the HPA axis and reduced brain volume in the hippocampus hasn't received a lot of attention, despite the fact that the most consistently reproduced findings in psychiatric patients with depression (but without MS) include hyperactivity of the HPA axis and smaller volumes of the hippocampus," Sicotte said.

"So the next step is to compare MS patients with depression to psychiatric patients with depression to see how the disease progresses in each," she said.