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The Mysteries of Multiple Sclerosis: Psychological Changes, Stress and the Immune System

by Patricia A. Farrell, Ph.D..

3 Credit Hours - $30
Last revised: 06/29/2017

Course content © Copyright 2009 - 2020 by Patricia A. Farrell, Ph.D.. All rights reserved.


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Learning Objectives

Symptoms of MS

The Stages of MS

Where MS does its Damage

MS Causation and the Mind-Body Connection

Illnesses Mistaken for MS

Cognitive Changes in MS

Mood Changes

Treatments and Strategies


References and Resources




Multiple sclerosis, often viewed as the most common neurologic, disabling disorder in young adults and teens in the US, affecting some 400,000 in the US, is an autoimmune disorder in which the body’s natural defense system experiences a dramatic breakdown resulting in destruction of portions of the nervous system.  It has been characterized as a biologically driven breakdown of the body’s communication from neuron to neuron.  This disruption in the delicate linkages between neurons is at the heart of the disorder.  Worldwide, the disease is estimated to affect over two million persons with its incidence being higher in certain areas of the world and lower in others.  Again, this adds to the question of causation.


Primarily known for its effect on vision, ambulation, and speech, it is often misdiagnosed, remains undiagnosed or is seen in a one-dimensional fashion that fails to recognize the psychological, cognitive challenges of the disease.


The disorder is so varied in both its presentation and in the symptoms that accompany it that the patient may go years before receiving treatment.  Proper diagnosis, however, may not always result in adequate treatment for all the symptoms owing to a lag in the understanding of how significantly the disease can affect the patient’s physical and psychological functioning.  When psychiatric syndromes are noted, treatment may be stymied because the disease may not respond as expected and this, too, deepens the mystery of how to most effectively treat the symptoms.






     Describe the Stages of MS

     Discuss where MS does its damage

     Explain MS and the mind-body connection

     List 3 cognitive changes in MS





As part of the course, please review the video What are autoimmune diseases? (click here to view).


One factor that has contributed greatly to the difficulty in diagnosing and treating MS is the purported number of symptoms associated with the disorder.  According to some researchers, the number of symptoms is well into the hundreds and some medical professionals have said it would be as high as one thousand.  In addition, there is no one set constellation of symptoms which would, together, point to an accurate diagnosis of MS.  Patients can have one seemingly insignificant and minor disruption in their body which comes and goes as quickly as it came.  Others will have symptoms that seem to strike in different parts of their bodies occasionally without getting worse. 


Symptoms of MS, as outlined by the National Multiple Sclerosis Society, cover a wide range of physical problems, the most common of which is fatigued.   Other physical symptoms which may be experienced can include the following:



Table 1. Other Physical Symptoms of MS




Walking (gait), balance and coordination problems

Bladder dysfunction

Bowl dysfunction

Vision problems which can often be of a transient nature or progressively worsen

Dizziness and vertigo

Sexual dysfunction


Cognitive impairment

Emotional lability or changes




These are among the most common problems experienced, however, there are symptoms which can be seen less frequently and they include:


Speech disorders

Swallowing problems


Hearing loss



Respiration/breathing problems




Although healthcare providers need to be conversant with the common as well as the infrequent symptoms of MS, this course will deal more specifically with the psychological aspects as well as how the disorder may arise and what areas of the nervous system will be affected. Multiple sclerosis has many different presentations and the waxing and waning of symptoms as well as the introduction of new symptoms often can be mislabeled as a psychological/psychiatric problem, especially in the case of depression (Siegert, & Abernethy, 2005; Raison, Capuron & Miller, 2006). Care should be taken to totally evaluate the individual, a careful and detailed history of symptoms as well as prior illnesses and areas of the world where this individual may have lived are all important factors that need to be included when a diagnostic evaluation is performed.


Inaccurate diagnoses of MS patients can include major depression, anxiety disorder NOS, bipolar disorder, dependent personality, panic disorder, forms of dementia, or adjustment disorders related to life circumstances or a combination of several disorders with characteristics of a variety of personality disorders. 


As part of the course, please review the video, Invisible symptoms of MS (click here to view).




Multiple sclerosis can present as a disorder of varying stages.   Some people may have a single episode and nothing more; however, the disorder usually follows one of four courses.   But even making an accurate assessment of which stages the patient manifests is problematic.  The usual stages include:


Relapsing–Remitting MS: a form with clearly defined attacks which worsen in terms of neurologic function. Attacks are often referred to as flair-ups,  relapses or exacerbations.   These flare-ups may be followed by partial or complete recovery and the illness may go into remission. According to experts, 85% of all people diagnosed with MS will exhibit the relapsing–remitting type.


Primary-Progressive MS: The individual will experience a slow, progressive worsening of symptoms without relapses or remissions. Progression varies greatly in individuals and there may be plateaus as well as temporary, minor improvements. Ten percent of people diagnosed with MS are in this category.


Secondary–Progressive MS:  May follow an initial relapsing-remitting stage where the disease now increases in its severity, there may be occasional flare-ups and minor remissions or plateaus. Prior to current treatments with disease-modifying medications about 50% of the patients progressed to this stage within 10 years after their diagnosis.


Progressive–Relapsing MS: is a rare stage of MS which is seen in about 5% of the patients, is characterized by a steady worsening with attacks indicative of worsening after the diagnosis. It is believed that this stage of the disease process may or may not have recovery potential.


These stages are so variable that healthcare professionals now know that no two individuals may have exactly the same disease progression.




As part of the course, please review the video, What happens in the central nervous system when a person has MS? (click here to view)


Three primary areas of the central nervous system (CNS) of an MS patient are affected: brain, optic nerves, spinal cord.  Within this complex CNS, neural structures fail the individual and begin on a path of destruction which may either be temporary and minor in nature, episodic or progressive in its deterioration of structures.


Although MS, we now know, has a significant effect on both cognitive processes and mood, it is usually seen as a disorder of vision, ambulation or speech. These are the most obvious, outward symptoms of the disorder and can often be mistaken for a number of other medical conditions. One of the single-episode MS symptoms sometimes seen may be optic neuritis and this may present suddenly and then disappear.




As part of the course, please review the video, Clinically isolated syndrome and optic neuritis (click here to view).


Tracing the destruction down to the cell level, we see that the immune system and its many components begin reacting as though there were a pathogenic invader. To do battle with this invader and to protect the individual’s health, the immune system begins to marshal its forces in terms of its natural killer T-cells, which results in inflammation of a portion of the nervous system; the neuron.


The neuron, the basic element of the nervous system, is comprised of the following structures:


The normal neuron allows an electrical charge to run smoothly down along the protective myelin sheath covering the axon.



Figure A: Normal Neuron


The damage to the neuron can be seen in Figure B that shows how the myelin sheath is attacked and left in a damaged condition.  This damage causes resulting symptoms of MS.



Figure B: Damaged Neuron


The cell body– where cell metabolism, production of neurotransmitters and a variety of other functions which maintain the viability of this entire cell are performed.


The axon–the cable-like structure which runs from the cell body to the dendrites (root-like structures) at the end of the axon where there are a variety of vesicles holding vital neurotransmitters.


The myelin sheath–a delicate fatty covering composed of Schwann cells over the axon which both protects and promotes effective transmission of an electrical charge which initiates neurotransmitter transport at the end of the axon.


Schwann cells–these are individual cells which make up the myelin sheath.   A series of single Schwann cells are each wrapped around the axon leaving small openings between each of these cells on the axon. The tiny space between the cells also promotes rapid electrical transmission.


The Nodes of Ranvier–this are the small openings between each of the Schwann cells on the axon.


Dendrites–root-like extensions which project from the cell body and form attachments to other cell bodies, glands and muscles.


The actual destruction which results from the normal disruption of the immune system takes place on the myelin sheath. It is here that the inflammatory process begins to degrade this fatty material, resulting in what is known as a sclerotic plaque.  The plaques or scars are consistent with MS and may be small or large causing minor physical problems or major disability.


What initiates this damage to the immune system?  The body, when under attack by pathogens, begins to release natural killer T-cells which set off a prolonged inflammatory reaction.  Usually, the object of the attack would be the pathogens, but here the object is the body tissue itself. Stress had always been seen as the key in initiating this process, but research is now bringing this hypothesis into question. As part of the course, please review the following videos:


The symptoms of multiple sclerosis (click here to view)


This is how I experience MS (click here to view)




What causes MS and the theories surrounding its development has been a subject of intense research and speculation since the disorder was first described by Jean-Martin Charcot in 1868.  The causes of the disorder still remain elusive, although several hypotheses have been tendered.  The current thinking is that there may be one or several causes, or perhaps a combination of factors which lead to the development of this neurodegenerative disorder.


Multiple sclerosis, as has been noted, is much more common in women than men. In fact, pharmaceutical manufacturers have noted a major discrepancy in terms of gender for a number of autoimmune disorders such as lupus where 90% of the patients are female, fibromyalgia where, again, 90% of the 3–6 million patients are female and rheumatoid arthritis where women are 2.5 times more likely than men to develop this disorder. Also, it is estimated that in Alzheimer’s disease two thirds of all Americans with the disorder are female.  This gender discrepancy in terms of certain disorders has not been satisfactorily accounted for and, certainly, in the case of MS, there appears to be no current theory prevalent for the reason that women develop MS at a higher rate than men.  There are about 400,000 persons with MS currently diagnosed in the US.


Numerous theories have been offered for the genesis of MS and, in the past, it was even suggested that women who had small dogs were at greater risk for developing MS. This theory was espoused after it was discovered that in some research studies large numbers of women with MS had small dogs. It was believed that there might be some pathogenic transmission between the small dog and its owner. This theory, however, is no longer in favor.


Theories, which have come to replace the prior “small dog theory,” have concentrated most heavily on the possible connection between:


Virus.  Early exposure to the Epstein-Barr virus is thought could result in its remaining dormant in the nervous system, much like the herpes or polio virus, and would present as an autoimmune disorder such as MS sometime in the future.  The Epstein-Barr virus, however, is only one of the viruses which have been suspected of being involved in this demyelination disorder.   Other viruses which have been investigated, at one time or another, include measles, herpes zoster, herpes simplex, rubella, mumps and a forest virus.   Some consideration was also given to respiratory infections and infectious mononucleosis.   The Epstein-Barr virus has remained as a primary interest as one of these suspected viral causes of MS for some 20 years.


Environmental.  A pattern of geographic location contributed to the belief that an environmental factor, such as something from pine trees, was also thought to be a root cause of MS.  This may have been based, in part, on the fact that many of the MS patients lived in cooler climates where pine trees were plentiful.  It was also thought that certain nationalities, which predominated in these areas, were at higher risk. Closer review of large studies has shown that other environmental factors, in addition to the latitude where some MS patients live, offer intriguing prospects for research.  For example, migration studies have found that anyone who migrated after adolescence to a different area of the globe (that has a lower incidence of MS) would carry the higher probability of developing MS found in the area from which they had migrated.  This geographic factor may be associated with exposure to sunlight, vitamin D or the month of birth. 


In one study, a higher incidence of MS was found in persons born in May as opposed to those born in November and was thought to be a result of the mother’s vitamin D status during pregnancy (Giovannoni & Ebers, 2007; Staples, Ponsonby & Lim, 2010).  The Epstein-Barr virus, however, has also been associated with infectious mononucleosis which may increase the risk of developing MS (Nielsen, Rostgaard, Nielsen, Koch-Henriksen, Haahr, et al., 2007).


Another aspect which has been explored is that of the psychosocial involvement of individuals with others (Malcomson, Dunwoody, & Lowe-Strong, 2007).


Blood circulation.  Research on what is called CCSVI (chronic cerebrospinal venus insufficiency) has indicated large numbers of MS patients have disruptions in their normal blood drainage from the brain and spinal cord.   One of the initial proponents of this CCSVI was Zamboni (Singh & Zamboni, 2009; Khalil, Tuenissen & Langkammer, 2011) who found venous flow differences in MS patients which did not appear in other neurodegenerative disorders such as Parkinson’s, Alzheimer’s and ALS. These flow disturbances they believed are caused by an abnormal mechanism of iron deposition in the venus vasculature.  The theory, however, is still controversial as is the surgery connected to it (Burton, 2010; Baracchini, Perini, Calabrese, Causin, Rinaldi, & Gallo, 2011). 


Stress.  Since stress has a negative effect on the immune system’s normal functioning and contributes to the increase in the stress hormone, cortisol, it is believed that intense stress could contribute to MS formation but there is some question about whether this is the singular factor causing the disorder or one of many contributory elements (Gold, Mohr, Huitinga, Flachenecker, Sternberg, et al., 2005; Mohr, Goodkin, Gatto, & Van der Wende, 1997). 


The stress hypothesis is intriguing because there is an apparent contradiction in it (Gold, Mohr, Huitinga, Flachenecker, Sternberg, et al., 2005).  Since stress hormones appear to ramp down the immune system, increased stress in an immune system that is already overly active should be beneficial in bringing this overactivity under control.  But that’s not the case.  According to Gold, this indicates just how complex the interactions are and he believes it is a paradox which further challenges researchers in MS (Farrell, 2011).


Further expanding on this stress hypothesis, Gold offers the case of MS patients who were in the war zone during Lebanon and Israel’s 33-day conflict.  Evaluation of stress levels in these individuals indicated there was a threefold increase in MS relapse in these patients. 


Patients reports of levels of stress and MS relapse were analyzed and it was found that they were experiencing an increased sense of helplessness.  This provided evidence of a link, Dr. Gold believes, between relapses in MS and helplessness, not necessarily just stress alone, but how stress can produce a change in the person’s belief system and their mood.  A sense of helplessness, as was outlined by Seligman (1975), can lead to depression which then has a feedback loop, according to Gold, into this biological process of inflammation. Helpless, too, has been seen as a mediating factor in both emotional instability and experienced fatigue in patients with MS (Van der Werf, Evers, Jongen & Bleijenberg, 2003).


This hypothesis of a stress-helplessness-depression loop provides new insight into depression in MS patients that has heretofore been seen as a reactive depression rather than a biological one.  The inflammatory markers found in depressed MS patients would appear to hold another clue to the genesis of the depression.


Interestingly, as Mohr et al. (2001) pointed out, treating the depression either through psychotherapy or medication can bring about a decrease in the inflammatory markers.  It is a clear indication of the bio-directionality of the immune system and the mind-body connection known as psychoneuroimmunology (PNI).   It has also been hypothesized (Mohr & Pelletier, 2006) that the psychosocial environment and the ability to cope may play a role in MS patients’ ability to contend with varying stressful events.  Barring this coping ability, individuals could be at greater risk of MS exacerbations.  Socialization, therefore, is seen as a vital component of effective treatment as is family involvement.


Genetic factors.   An overview of both the infection and genetic factors in MS causation (Murray, 2002) in siblings and fraternal twins indicates it can vary.   Siblings and fraternal twins have about a 2-5% higher incidence of MS than the normal population. Identical twins, however, have about a 30% higher chance of developing MS that may indicate further evidence for a strong genetic factor.  Researchers note that there may also be a genetic predisposition in some individuals to develop a viral infection that then compromises the blood-brain barrier and begins the inflammatory process and its destructive cascade in the immune system.


Studies pointing to an inherited predisposition to develop MS with children of patients having a higher risk for the disorder may have failed to consider other applicable variables.  There exists, as was noted, the possibility that there could be an additional environmental factor, not solely a genetic one, since families live with their children in specific environments, e.g., housing, country, cultural and dietary factors, etc.


The disproportionate number of women who develop MS has not been adequately explained, although it is noted that the largest pool of women with MS lies within the child-bearing years from 20-40. There is, however, no absolute cut-off age for developing MS in women or men.


Multiple sclerosis, also, is not a disorder that is only found in adults since it has been diagnosed in infants, children and teenagers. This would lead one to question whether or not there is more than one mode of infection other than the proposed Epstein-Barr or shingles virus theory. As noted earlier, it could be related to the vitamin D status of their mothers during pregnancy.


Illnesses Mistaken for MS


Many illnesses that primarily have a neurologic dysfunction may, interchangeably, be mistaken for MS and vice-versa.   An incorrect diagnosis may have deadly consequences such as that of a woman misdiagnosed with MS who, in fact, did not have it but had another disorder known as PML (Poser, 2008). Several of these disorders that mimic some of the symptoms of MS are shown here in Table 2.



Table 2. Illnesses that Mimic MS



Acute Disseminated Encephalomyelitis

Amyotrophic Lateral Sclerosis

Arnold-Chiari Deformity



Dural Arteriovenus Fistulas


Human T-cell Lymphotophic Virus


Lyme Disease

Mitochondrial Disorders

Muscular Dystrophy

Myasthenia Gravis



Sjogren’s Syndrome


Systemic Lupus Erythematosus

Vitamin B-12 Deficiency





Usually thought of as primarily a disorder of the musculoskeletal system resulting in problems walking, standing, talking or maintaining balance, MS has less obvious, but no less challenging symptoms, of a cognitive nature.  These, perhaps more than the motoric problems, rob the person of self-esteem, bring on depression and anxiety, diminish memory and concentration and disrupt vocational, social and educational efforts.  MS can also cause physical changes in the hippocampus, the brain structure most associated with acquiring memory.  Research has also noted the involvement of immunity inflammation in depression (Gold & Irwin, 2006; Irwin & Miller, 2007).


Seemingly psychiatric problems include one especially bizarre symptom.  Pathological laughing and crying (PLC) is an unusual symptom found in 10% of persons with multiple sclerosis (Parvizi, Coburn, Shillcutt, Coffey, Lauterbach & Mendez, 2009).  Its presentation of inappropriate or exaggerated outbursts of laughing and crying absent of appropriate feelings can be misdiagnosed as psychosis.  PLC may appear in several forms; only laughing, only crying or both laughing and crying (Cummings, Ariniegas, Brooks, Herndon, Lauterbach et al, 2006).


Believed to be a neuroanatomic problem, the exact site or sites of the affected areas that bring on PLC have not been established.  A possible hypothesis is that a type of dysregulation caused by brain damage may underlie the condition. 


Other, more subtle changes, of cognition in terms of memory, concentration and even mood changes, have also been seen in most if not all MS patients. Here, however, rather than being seen as a potential problem of a medical diagnosis, the subtleties can often be dismissed as the result of being overly involved in some activity, having too many things to remember, or just the normal activities of our everyday lives, especially when young children are involved.  All of the MS patients with problems, however, have clear indications of brain damage on scans.


For children these hidden symptoms of MS can be extremely damaging.  The lack of concentration and memory impairment as well as the fatigue they experience diminish their ability to do school work (Weisbrot, Ettinger, Gadow, Belman, MacAllister et al, 2010).  This disruption of their ability to do schoolwork has a direct impact on their self-esteem, socialization and academic performance.  Often, MS is not recognized in children immediately because it is seen as a disorder of adults.  Behavioral problems, too, whether in class or at home may be seen as stubbornness or “acting out” when it is MS-initiated mood swings (MacAllister, Belman, Milazzo, Weisbrot, Christodoulou, et al. 2005).


Multiple impairments brought on by MS’s cognitive changes affect all aspects of everyday life and learning and are found in both children and adults.  These impairments include the following:



Table 3. Cognitive Changes Affecting Everyday Life



Problems in the ability to learn


Memory or recall problems


Organizational skills and planning


Maintenance and shifting of attention


The use of appropriate language


Correctly perceiving what is happening in the environment


The ability to do simple calculations and to perform necessary and personal or job-related financial activity



Memory problems may come on slowly and can interfere with overlearned simple tasks such as driving to a familiar location like a supermarket or a child’s school.  Then, too, the fact that there is little to no discernible pattern of disabilities associated with MS further confounds the diagnosis in both children and adults.  Multi-symptomed and with ebbs and flows of difficulties can play havoc with the individual who has MS.  It is a fertile environment for insecurity and is especially corrosive to socialization and life planning.


Case:  Kevin, a man in his mid-40


A career professional, Kevin had a crack memory, effectively juggled many projects at a time and never seemed to need to cut back.  But now there was something different happening to this young father.  Slowly, as his workdays progressed, he found not only that he was having problems remembering simple routines he did almost without thought previously.  Now, he fumbled for words, read material multiple times and still had problems recalling what he had just read.  His neurologist finally diagnosed MS, but told him all he needed to do was to go home and rest.  It was an inadequate solution for a problem that was robbing him of his very being. His MS had not been diagnosed immediately, but once it was, he realized that he could no longer engage in his regular career activities, couldn’t effectively handle the family finances and would have to retire early on disability and get accounting help.  He also realized that his neurologist had a dismal view of MS and any possibilities for rehabilitation; he’d need a second opinion.


Another opinion was sought and Kevin had a complete neuropsychological evaluation (which the first neurologist never ordered) and which pointed more precisely to his symptoms, his potential and to his diagnosis.  He was referred for ongoing treatment with a neurologist and a neuropsychologist.  The treatment was not to “rest” but to remain active in new ways so that he could continue his life, but within certain parameters.   Not only did his work life change dramatically as he scaled down his activities and then left his firm, but other aspects of his life needed to be changed, also.


He discovered that he would often find himself driving and then not remember what his destination was. Not only could he not remember the destination to which he planned to go, but also much of the usually familiar streets, signposts, and landmarks were all now unfamiliar. The drive, which would normally be without incident, became a terrifying experience as he tried to recall where he was going and where he needed to turn his car. There seemed to be nothing that was giving him a clue. Gradually, as he sat on the side of the road in his car waiting to marshal his memory resources, it occurred to him that he was driving home. It had been a totally unnerving experience and it had to result in some significant changes in how he would drive in the future.


Driving wasn’t the only new challenge that Kevin had to meet. Teaching courses on the college level, he found himself standing before his students and not knowing what he had just discussed during the lecture. His mind was a blank and he depended on his students to refresh the discussion and to help him to contribute. It was both upsetting and, as he felt, professionally compromising to his reputation. The sea of expectant student faces didn’t help matters as he frantically tried to recall his train of thought on a particular subject. It couldn’t go on.   Students didn’t see any obvious impairment as he walked into the room for each lecture and they were totally unaware of his internal struggle with MS.   It was robbing him of a sharp memory that had served him well for many years.


Kevin is working with a therapist who understands that it’s not just a memory problem; it’s a memory recovery as well as an acquisition problem.  The previously learned facts are there, but he can’t find them as quickly as he wants.  He now writes out not only what he has to do that day but provides himself with a roadmap that indicates all of the turns he needs to make in the car in order to get to his destination.   It is all quickly visible next to him from the spot where it is pasted on the dashboard of his car. There are also reminders in the house in terms of calendars and notebooks next to the telephone.  If he receives a call and information that he needs to remember is conveyed to him, it is immediately transcribed into the notebook and then to the calendar.


Case:  Maria, a young mother of pre-teen children


Maria is a young woman who is involved in a demanding job which can be, at times, quite stressful. She and her husband had always been quite active in the community where they enjoyed socializing with their many friends and involved themselves in group activities as well as extended family camping vacations.   Fatigue was one of the first things that became apparent to her, as she found that her energy was easily sapped and she could no longer maintain the activity level that she had been enjoying previously. 


She also found that she easily lost her way while going to the supermarket, could not remember what she had set out to buy, and even, on at least one occasion, could not remember whether she had picked the kids up at school or not. It panicked her as she feverishly tried to remember whether or not she had even taken them to school that morning and whether she could have picked them up or forgotten them. Where were the children now, was her immediate thought and were they in any type of danger?


As a result her of experiences, she has now put into place things that will enable her to keep track not only of her daily schedule, but of things that she plans to do and where she is going to go when she gets into her car.


Maria uses a small tape recorder to record all of the activities before she leaves the house and then carries it in her purse everywhere she goes. It serves as a good verbal reminder. She never leaves home without her memory aid.


Case:  Cynthia, a straight-A college student


Cynthia, an 18-year-old college student with a previous record of superior academic performance and who had received almost straight A’s in high school, was now in college. Gradually, behavioral changes were being noted as she found she had problems not only concentrating on her studies, but with rapid changes in her mood and energy levels. On several occasions, she found that her memory was “going blank,” as she described it, during tests and the material no longer came quickly to her.  Instead of being the first to put her paper down, she now found herself sitting in the room almost until the end of the test period.  Never before had she needed extra time for tests or a special, quiet room to take her tests.  Concentration had never been a problem.


She began to engage in a number of activities at school such as running for class representative in her demanding nursing courses, joined several clubs and then found herself unable to pull herself up from her bed in the morning. Her grades were steadily going down and her self-esteem was, similarly, sliding rapidly as she began to question her abilities in school.


The first thought in her parents’ minds was that she wasn’t applying herself as she had in high school and they referred her to a counselor. The counselor felt she was being attention seeking because she was living away from home and that she was making a poor adjustment to college. Everyone assumed it was just a young woman who was having problems adjusting to new demands and a new environment. The parents were told that even the vision problems and unsteadiness on her feet, too, were simply psychological in nature.


The counselor, assuming it was psychological, told her parents that it was just another attempt to return home to a less stressful community college experience. No one believed that a medical examination was called for since everything was being attributed to psychological adjustment.


Fortunately, Cynthia developed the flu and was placed in the college infirmary where the physician began noting her history. It was this history taking that began the process that led to the diagnosis of MS. It was also this fortuitous hospitalization that helped everyone realize Cynthia was not attention seeking; she was ill.  She began that summer to attend one of the specialized camps for teens with MS.  Having an opportunity to talk to other teens about her difficulties was, as she said, “One of the greatest things because I wasn’t alone and everyone understood and I was believed.”




Mood changes are a symptom associated with MS and, interestingly, changes in portions of the brain that have to do with memory, i.e., the hippocampus, are also associated with this. In individuals with MS, brain studies and psychological testing have shown deterioration in the hippocampus, memory deficits and associated depression (Bremer, Narayan, Anderson, Staib, Miller & Charney, 2002).


One common feature that is normally seen in depressed individuals, fatigue or lack of motivation, when it presents in patients with MS has been associated with a progressive atrophy of the corpus callosum but the association has not yet proven to be the major factor in MS depression (Yaldizli, Glassl, Sturm, Papadonopoulu, Gass et al., 2011).  Researchers believe that MS-related fatigue still remains unexplained and unpredictable.


Is depression in MS patient, then, a result of immune system initiated chronic inflammation that results in apoptosis, aka cell death, in vital brain structures related to mood and anxiety levels?  Or is it that the depression is somehow related to or causes the shrinkage in the hippocampus that results in memory loss and then that decline in cognitive sharpness further exacerbates the person’s depression?  These are interesting questions that are yet to be answered.


A fascinating discovery has been the association between exercise, mood and neurogenesis.  The theory is that exercise may actually do two things; regulate mood via neurotransmitter production and, possibly, help the body to promote brain cell growth (Hillman, C.H., Erickson, K.I., & Kramer, A.F., 2008; Hamer & Chida, 2009).  The old myth that we were born with all the brain cells we would ever have has been shown to be incorrect and we have seen that we can produce new brain cells (Deng, Aimone & Gage, 2010).


Ongoing research in the area of exercise as it relates to brain gray matter volume and white matter integrity is now beginning to show some results (Prakash, Snook, Motl, & Kramer, 2009).  It was the opinion of these researchers that, “Taken together, these results suggest that fitness exerts a prophylactic influence on the structural decline observed early on, preserving neuronal integrity in multiple sclerosis, thereby reducing long-term disability.”


Ironically, the very activity that might permit MS patients to regain some memory function that was lost as well as brighten their mood is undermined by the fatigue that the illness brings.  Exercise for some seems almost out of the question.  The fear is that exercise raises the body’s core temperature leading to symptom exacerbation. Currently, however, these are seen as pseudoexacerbations and exercise is now in the spotlight as an integral part of treatment.




While there is currently no cure for MS, a variety of pharmacologic interventions have been formulated and these include medications that have become known as the “ABC” treatments as well as the formerly used steroids for inflammatory disorders.


These ABC medications work by modifying some aspects of the immune system and they include:






Newer medications continue to come from research.  However, at lest one newer medication has been found, in some patients, to cause a rare brain infection.  This side effect, known as progressive multifocal leukoencephalopathy (PML) is associated with Tysabri.  PML can cause death or severe disability. The side effect has resulted in selecting patients for this treatment only from the group that has not shown sufficient help or tolerance for other medications.


Psychotropic medications can also be used to help alleviate the depression and mood swings found in most MS patients. Unfortunately, these medications are not always effective because the immune system and the mood dysfunction it causes are not always responsive to these interventions.


In addition to medications, because of the cognitive and mood disorders found in persons with MS, a variety of behavioral interventions have been formulated. These interventions are aimed primarily at memory and concentration involvement as well as helping the patient to maintain their self-esteem, social involvement and also utilize exercise in a totally new way.


Exercise, as has been noted, was formerly thought to be disadvantageous for MS patients since it raised the body’s core temperature. This perspective has now been dramatically changed because of important discoveries regarding exercise, memory, depression and the nervous system in terms of potential nerve repair.




Research has shown that exercise plays a significant role in promoting brain-derived neurotropic growth factor (BDNF) and BDNF may play a significant role in MS (Castellano & White, 2008; Linker, Lee, Demir, Wiese, Kruse et al., 2010).   Magnetic resonance imaging has shown that groups who were physically fit as opposed to those who were less fit, had a protective effect on their brains caused by their physical fitness. Conclusions on samples of physically fit individuals showed that they did better on tests of cognition, processing speed and attention span.


There appears to also be a significant effect on memory and attentional control (Prakash, Voss, Erickson, Lewis, Chaddock, et al. 2011).   This study, the researchers assert, provides evidence for fitness and its effects on the responsiveness of neural circuits involved in attentional control. They note that additional research has established the contribution of exercise to increased volume in hippocampi of older adults (Erickson, Prakash, Voss, Chaddock, Hu, et al., 2009b).


Even walking was found to improve cognition in older adults and the pace of the walking was seen as inconsequential. It was simply walking for periods of time that was seen as the important variable.


Learning new physical skills, too, such as juggling was found to initiate changes in the white matter of the brain, which is linked to reaching, grasping, and peripheral vision. The suggestion of researchers was that it didn’t matter which type of exercise was performed, only that some form of physical or mental exercise was regularly engaged in. Suggestions included crossword puzzles and walking.


The beneficial effects of exercise on brain substances such as endorphins, which are often called the “feel good” neurotransmitters, as we know, also affect mood.  Since mood changes play a major role in the lives of persons with MS, exercise could provide an additional benefit and enable these individuals to better maintain their social and vocational aspects of their lives.


Resilience-building Behaviors


Multiple sclerosis presents additional challenges to patients in terms of maintaining a positive attitude toward their lives and it is here that resilience plays a major role. Psychologists have suggested that a sense of resilience in the face of this chronic illness can be developed in several ways. The steps that have been suggested include:


Actively joining groups such as a local support group

Accepting that things will change throughout the course of the illness

Setting realistic goals and a regular schedule to meet them in small ways, each day

Initiate a search for self-discovery and personal growth

Finding something that enriches an aspect of their lives


Everyday Memory Problems


Memory problems for patients with MS have been described not so much as a lack of memory but a lack of acquisition and consolidation of memories, but usually not of retrieval. It is here that new research is being performed regarding what is called “self-generated memories” (Chiaravalloti, DeLuca, Moore, & Ricker, 2002; Chiaravalloti, Demaree, Gaudino, & DeLuca, 2003; Basso, Lowery, Chormley, Combs, & Johnson, 2006).


Self-generated memories reinforce the patient’s ability to acquire and consolidate information and the caregiver or spouse’s ability to help them with this. In this way, it is a two-person form of memory enhancement. The process is quite simple.  Instead of someone constantly reminding the patient of something they need to remember, the person cues the patient with phrases that will initiate memory retrieval.


When something is needed in the home or at the store, the spouse might indicate, “We need some of that stuff we put in our coffee.” The person now has to think of what that item is and that begins the process of memory generation.   So the patient is not told what to remember but given a task of memory generation.




Chronic illnesses, such as MS, inevitably can produce in the patient feelings not only of depression, but of failure, being overwhelmed and isolated. It is these aspects of an illness that can be addressed through Dr. Adam Kaplin’s suggestion of teaching remoralization (Kaplin, 2007).  This, in effect, is a way to help patients establish a sense of mastery and new problem-solving techniques. The steps that Kaplin has suggested include:


Building rest periods into the day to deal with fatigue

Maintaining social group involvement to deal with the sense of isolation

Education regarding coping strategies

Shopping at off-peak hours so as not to feel rushed

Re-examining beliefs about the individual’s gains in terms of the illness.

Every gain, no matter how small, should be seen in a positive light.


The basic premise of remoralization is to help the patient make adjustments and adaptations regarding what is reasonable for them to do in their lives in terms of their abilities.   This framework is intended to help decrease life stressors and feelings of anxiety.   Remoralization, therefore, is a form of cognitive restructuring which the patient learns to do for themselves.




Multiple sclerosis, as you have seen, is a highly variable, often difficult to diagnose, incurable neurodegenerative disorder that always brings with it unseen or underappreciated cognitive dysfunction in terms of mood, memory, concentration and even perceptual problems in children and adults.  It is chronic but both psychotherapy and psychopharmacology have been shown to be effective in treating the depression experienced by some MS patients.  Self-help techniques, too, are mandated in order to bolster the patient’s abilities to maintain themselves within the confines of their illness and to help with their sense of self-esteem.




Accelerated Cure Project for Multiple Sclerosis:


American Autoimmune Related Diseases Association:


American Psychological Association (2010).  The road to resilience.  Accessed online February 2010.


Baracchini, C., Perini, P., Calabrese, M., Causin, F., Rinaldi, F., & Gallo, P. (2011).  Annals of Neurology, 2011, 69(1), 90-99.


Basso, M.R., Lowery, N., Chormley, C., Combs, D., & Johnson, J. (2006).  Self-generated learning in people with multiple sclerosis.  Journal of the International Neuropsychological Society, 12, 640-648.


Bremner, J.D., Narayan, M., Anderson, E.R., Staib, L.H., Miller, H.L., & Charney, D.S. (2000) Hippocampal volume reduction in major depression.  American Journal of Psychiatry, 2000, January, 157(1), 115-8.


Castellano, V., & White, L.J. (2008).  Serum brain-derived neurotrophic factor response to aerobic exercise in multiple sclerosis.  Journal of the Neurological Sciences, 269, 85-91.


Chiaravalloti N., DeLuca J., Moore N., & Ricker JH. (2002) Cognitive remediation as treatment for new learning deficits in multiple sclerosis. The International Journal of MS Care, 4, 77.


Chiaravalloti N., Demaree H., Gaudino EA., & DeLuca J. (2003) Can the repetition effect maximize learning in multiple sclerosis? Clinical Rehabilitation, 17, 58-68.


Cummings, J.L., Ariniegas, D.B., Brooks, B.R., Herndon, R.M., Lauterbach, E.C., Pioro, E.P., Robinson, R.G., Scharre, D.W., Schiffer, R.B., & Weintraub, D. (2006).  Defining and diagnosing involuntary emotional expression disorder.  The International Journal of Neuropsychiatric Medicine, CNS Spectrums, June 11(6), 1-7.


Deng, W, Aimone, J.B., & Gage, F.H. (2010).  New neurons and new memories:  How does adult hippocampal neurogenesis affect learning and memory?  Nature Reviews Neuroscience, 1-12.  Published online March 2010.


Erickson, K. I., Prakash, R. S., Voss, M. W., Chaddock, L., Hu, L., Morris, K. S., White, W. M., Wojcicki, T. R., McAuley, E., & Kramer, A. F. (2009b). Aerobic fitness is associated with hippocampal volume in elderly humans. Hippocampus 19, 1030–1039.


Farrell, P.A. (2011). It’s Not All in Your Head:  Anxiety, Depression, Mood Swings and Multiple Sclerosis.  New York:  Demos Health Div. of Demos Medical Publishing LLC.


Giovannoni, G. & Ebers, G. (2007).  Multiple sclerosis:  The environment and causation.  Current Opinions in Neurology, 20, 261-268.


Gold, S.M., & Irwin, M.R. (2006).  Depression and immunity inflammation and depressive symptoms in multiple sclerosis.  Neurological Clinics, 2006, 24, 507-19.


Gold, S., Mohr, D.C., Huitinga, I., Flachenecker, P., Sternberg, E.M., & Heesen, C. (2005) The role of stress-response systems for the pathogenesis and progression of MS.  Trends in Immunology, 26(12), December.


Hamer, M. & Chida, Y. (2009).  Physical activity and risk of neurodegenerative disease:  A systematic review of prospective evidence.  Psychological Medicine, 39, 3-11.


Hillman, C.H., Erickson, K.I., & Kramer, A.F. (2008).  Be smart, exercise your heart: Exercise effects on brain and cognition.  Nature Reviews Neuroscience, 9, 58-65.


Irwin, M.R., & Miller, A.H. (2007).  Depressive disorders and immunity:  20 years of progress and discovery.  Brain, Behavior and Immunity, 21, 374-383.


Kaplin, A. (2007).  Depression in multiple sclerosis.  In J. A. Cohen & R. A. Rudick (Eds.),  Multiple Sclerosis Therapeutics, 3rd ed., pp. 823-844.  London:  Informa Healthcare.


Khalil, M., Teunissen, C., & Langkammer, C. (2011).  Iron and neurodegeneration in multiple sclerosis.  Multiple Sclerosis International, 2011.  Retrieved online June 2011.


Linker, R.A., Lee, D.H., Demir, S., Wiese, S., Kruse, N., Siglienti, I., Gerhardt, E., Neumann, H., Sendtner, M., Luhder, F., & Gold, R. (2010).  Functional role of brain-derived neurotrophic factor in neuroprotective autoimmunity:  Therapeutic implications in a model of multiple sclerosis. Brain, 133(Pt. 8), 2248-2263.


MacAllister,W.S., Belman, A.L., Milazzo, M., et al.  Cognitive functioning in children and adolescents with multiple sclerosis. (2005)  Neurology 64, April, 1422-1425


Malcomson, K.S., Dunwoody, L., & Lowe-Strong, A.C. (2007). Psychosocial interventions in people with multiple sclerosis:  A review.  Journal of Neurology, 254, 1-13.


MacAllister, W.S., Belman, A.L., Milazzo, M., Weisbrot, Christodoulou, C., Sherl, jW.F., Preston, T.E., Cianciulli, C., & Krupp, L.B. (2005).  Cognitive functioning in children and adolescents with multiple sclerosis. Neurology, 64(8), 1422-1425.


Mohr, D.C., Goodkin, D.E., Gatto, N., & Van der Wende, J. (1997). Depression, coping and level of neurological impairment in multiple sclerosis. Multiple Sclerosis, 3, 254-258.


Mohr, D.C., Goodkin, D.E., Islar, J., Hauser, S.L., & Genain, C.P. (2001).  Treatment of depression is associated with suppression of nonspecific and antigen-specific TH1 responses in multiple sclerosis. Archives of Neurology, 58, 1081-1086.  Retrieved online June 2011.


Mohr, D.C., & Pelletier, D. (2006).  A temporal framework for understanding the effects of stressful life events on inflammation in patients with multiple sclerosis.  Brain, Behavior and Immunity, 20, 27-36.


Multiple Sclerosis Association of America:


Murray, J. (2002).  Infection as a cause of multiple sclerosis: Theories abound because no one knows the answers yet.  British Medical Journal, 325(16), 1128.  Retrieved online May 2011.


Newland, P.K., Naismith, R.T., & Ullione, M. (2009).  The impact of pain and other symptoms on quality of life in women with relapsing-remitting multiple sclerosis.  Journal of Neuroscience Nursing, 41(6), 322-328.


Nielsen, T.R., Rostgaard, K., Nielsen, N.M., Koch-Henriksen, N., Haahr, S., Sorensen, P.S., & Hjalgrim, H. (2007).  Multiple sclerosis after infectious mononucleosis.  Archives of Neurology, 64, 72-75.


Parvizi, J., Coburn, K.L., Shillcutt, S.D., Coffey, C.E., Lauterbach, E.C., & Mendez, M.F. (2009).  Anatomy of pathological laughing and crying: A report of the American Neuropsychiatric Association Committee on Research. Journal of Neuropsychiatry and Clinical Neuroscience, 21(1), 75-87.


Poser, C.S. (2008). The treatment of multiple sclerosis with beta-interferon.  Neuroepidemiology, 31, 157-158.


Prakash, R.S., Snook, E.M., Motl, R.W. & Kramer, A.R. (2009).  Aerobic fitness is associated with gray matter volume and white matter integrity in multiple sclerosis.  Brain Research. Retrieved online June 2011.


Prakash, P.S, Voss, M.W., Erickson, K.I., Lewis, J.M., Chaddock, L., Malkowski, E., Alves, H., Kim, J., Szabo, A., White, S.M., Wójcicki, T.R., Klamm E.L., McAuley, E., & Kramer, A.F. (2011).  Cardiorespiratory fitness and attentional control in the aging brain.  Frontiers in Human Neuroscience, 4, 229, 1-12.


Raison, C.L., Capuron, L., & Miller, A.H. (2006).  Cytokines sing the blues:  Inflammation and the pathogenesis of depression.  Trends in Immunology, 27(1), January, 24-31.


Seligman, M.E.P. (1975).  Helplessness: On depression, development and death.  San Francisco:  W.H. Freeman.


Siegert, R.J. & Abernethy, D.A. (2005).  Depression in multiple sclerosis:  A review.  Journal of Neurology, Neurosurgical & Psychiatry, 76, 469-475.


Singh, A.V. & Zamboni, P. (2009).  Anomalous venus blood flow and iron deposition in multiple sclerosis.  Journal of Cerebral Blood Flow & Metabolism, 29, 1867-1878. 


Staples, J., Ponsonby, A., & Lim, L. (2010).  Low maternal exposure to ultraviolet radiation in pregnancy, month of birth, and risk of multiple sclerosis in offspring:  Longitudinal analysis.  British Medical Journal, 340.  Retrieved online June 2011.


Van der Werf, S.P., Evers, A., Jongen, P.J.H., & Bleijenberg, G. (2003).  The role of helplessness as mediator between neurological disability, emotional instability, experienced fatigue and depression in patients with multiple sclerosis.  Multiple Sclerosis, 9(1), 89-94.


Van der Werf, S.P., Evers, A., Jongen, P.J.H., & Bleijenberg, G. (2003).  The role of helplessness as mediator between neurological disability, emotional instability, experienced fatigue and depression in patients with multiple sclerosis.  Multiple Sclerosis, 9(1), 89-94.


Weisbrot, D.M., Ettinger, A.B., Gadow, K.D., Belman, A.L., MacAllister, W.S., Milazzo, M., Reed, M.L., Serrano, D., & Krupp, L.B. (2010).  Psychiatric comorbidity in pediatric patients with demyelinating disorders.  Journal of Child Neurology, 25(2), 192-202.


Yaldizli, O, Glassl, S., Sturm, D., Papadoupoulou, A., Gass, A., Tettenborn, B., & Putzki, N. (2011).  Fatigue and progression of corpus callosum atrophy in multiple sclerosis.  Journal of Neurology. Published online May 19, 2011.



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