A comprehensive study published in the September 27, 2007 edition of the New England Journal of Medicine ¹ has demonstrated “no causal association” linking exposure to a mercury-based preservative used in routine childhood vaccines to abnormalities in later neuropsychological development.

The preservative, known as thimerosol, is approximately 50% (by weight) mercury and had been used as a preservative in a number of biological preparations since the mid 1930s.

In the recent study, a team headed by William Thompson, PhD of the US Centers for Disease Control and Prevention administered a battery of 42 neuropsychological tests to a panel of 1,047 children aged 7 to 10 years at the time of the examinations.  Exposure to thimerosol was determined from vaccination records and/or the recollections of each child’s parent.

The study found that there were very few associations between thimerosol and the results of the neuropsychological tests, with both positive (better than expected performance) and negative (less than expected) associations being equally present.  This was in contrast to reports from 3 previous studies in which 1 study found that there was a slightly higher association of lower scores on neuropsychological among children that had received vaccines containing thimerosol,  1 study found a slightly lower association, and a study that found no relationship.

The authors of the study were quick to point out that they did not specifically address the question of a possible causal link between thimerosol and autism or “autism spectrum disorder,” leaving that question to be answered by ongoing studies specific to that topic.

In related commentary published in the same issue of the New England Journal, ² Paul Offit, chief of the Division of Infective Diseases at the Philadelphia (PA) Children’s Hospital reviewed the history of the thimerosol controversy and stressed that the decision of the US Food and Drug to ask vaccine makers to investigate whether alternatives to thimerosol could be used and to voluntarily cease thimerosol use when such alternates were proven safe.

Dr. Offit also noted that the report’s findings will probably meet with a chorus of protest from those who have, in the absence of scientific evidence, attempted to link thimerosol to autism for reasons involving potential financial or political gains.

“Despite several years of reassuring studies, the thimerosol controversy continues to be emotionally charged. Physicians, scientists, government policy advisors, and child advocates who have publicly stated that vaccines don’t cause neurologic problems or autism have been harassed, threatened, and vilified, receiving hate mail and occasionally death threats. The CDC, in response to planned protests at its gates, recently beefed up security and instructed personnel about how to respond if physically attacked.”

Commentary

Normally, at this point, I would present some additional commentary or personal observations on the topics mentioned above.  I will not do so simply because most people have already made up their minds on these issues and no amount of evidence will be sufficient to force a change.

For those readers interested in reading a balanced and impartial review of the ongoing legal controversy regarding vaccines and autism, see Stephan Sugarman’s “Cases in Vaccine Court – Legal Battles over Vaccines and Autism” in the same issue of the New England Journal. ³

For those who have decided the issue, based on their own prejudices and/or motivations, I ask only that you be honest with yourselves.

Notes

1. Thompson, William W; Price, Cristofer; Goodson, Barbara; Shay, David K, and Benson, Patti et al. Early Thimerosal Exposure and Neuropsychological Outcomes at 7 to 10 Years, NEJM (September 27, 2007) 357: 13, 1281-1292.

2. Offit, Paul A. Thimerosal and Vaccines — A Cautionary Tale, NEJM (September 27, 2007) 357: 13, 1278-1279.

3. Sugarman, Stephen D. Cases in Vaccine Court – Legal Battles over Vaccines and Autism, NEJM (September 27, 2007) 357: 13, 1275-1277.

An article to appear in the October, 2007 issue of the journal Nature Reviews Neuroscience ¹ will present the strongest evidence to date that a form of vitamin A known as retinoic acid may be of value in the treatment of conditions such as Alzheimer’s and Parkinson’s diseases.

While vitamin A-complex (meaning the vitamin itself as well as chemically-related organic compounds) has long been known to be essential for normal cell growth and efficiency, the report is the first to link the substance with a reduced rate of cell loss in the brain and an enhanced ability to repair and/or re-grow damaged nerve cells.  Earlier research had demonstrated that a breakdown in the mechanisms by which these substances are transported from the intestine to the brain could be involved in Alzheimer’s disease. ²

Comment

For those who are familiar with the ongoing debate on the value of nutritional supplements in general, the momentum seems to be shifting to those advocating that vitamin A supplements are valuable in slowing down the progression of the broad class of medical conditions known as the neurodegenerative diseases (such as Alzheimer’s or Parkinson’s diseases). However, the above-mentioned report is based on laboratory studies only and not on controlled studies in humans.

It must also be stressed that the use of vitamin A is not without risks in its own right. The “For More Information” links below should be consulted, along with one’s health care provider, before taking any form of vitamin supplements.

For More Information

The National Institutes of Health’s Office of Dietary Supplements’ fact sheet on Vitamin A can be found at http://ods.od.nih.gov/factsheets/vitamina.asp

The US Food and Drug Administration’s information for older consumers regarding dietary supplements and related issues can be found at http://www.cfsan.fda.gov/%7Edms/ds-savv2.html. (This page hasn’t been updated recently, so use your own judgment when considering its contents).

Notes

1. Malcolm Maden: Retinoic acid in the development, regeneration and maintenance of the nervous system, Nature Reviews Neuroscience (October, 2007) 8: 755-765

2. Ann B. Goodman and Arthur B. Pardee: Evidence for defective retinoid transport and function in late onset Alzheimer’s disease, PNAS (March 4, 2003) 100: 5, 2901-2905

For years those that have received chemotherapy as part of their treatment for cancer have been reporting a set of neurological symptoms that include difficulties with short-term memory and decision-making that developed after receiving anti-cancer medical therapy.  These symptoms, informally called “chemo-brain” or “chemo-fog,” are finally being recognized and studied by researchers in fields from psychology to cancer treatment. ^{1, 2}

The symptoms attributed to chemo-brain are quite varied, but two subsets of these symptoms seem to be the most prevalent.

The first subset involves difficulties with what are known as the “executive functions” of the brain, the process by which the brain makes decisions regarding priorities or deciding on a course of action.  As an example, those with chemo-brain have reported problems deciding in what sequence a set of actions, such as shopping at different locations, should be performed.

The second subset of symptoms, those involving problems with short-term memory, seems to be the most prevalent.  Short-term memory is the process by which “new” information, such as a person’s name, is “remembered” until the brain makes a decision concerning whether the information should be retained or discarded.  In another example, one woman reported that she was unable to remember the scores during her son’s high school tennis matches even though she had taught her son the game and was an accomplished amateur in her own right.

There are, of course, many medical conditions that are known to cause the same symptoms as those associated with chemo-brain.  These conditions include:

·         Stress, which is probably the most common cause of memory problems.  Since treatment for cancer is both emotionally and physically stressful, researchers are investigating whether stress is a possible contributing factor in chemo-brain.

·         Hormonal imbalances are also associated with difficulties involving both memory and executive functions.  The fact that hormonal therapy is an important part of cancer therapy, particularly in women, has led some researchers to propose that chemo-brain may be related to changes in hormonal levels in chemotherapy.

The reader desiring more information on these topics will be well-served by consulting the links in the “For More Information” section of this posting.

As an aside, the symptoms reported in chemo-brain are very similar to those reported by patients that have undergone heart surgery using heart-lung bypass (meaning that the heart was stopped during surgery and the body’s oxygen requirements were met by using “the pump”).  Interestingly, the growing use of “off-pump” surgical techniques (the heart is not stopped during surgery) has been associated with a dramatic decrease in post-operative neuro-psychological problems. ^{3, 4}

Comment

The recent research activity involving the possible causes of “chemo-brain” is both encouraging and fascinating.  Finally, this set of self-reported symptoms has caught the attention of the medical community. It is encouraging to the literally thousands of patients that have received “chemo” as part of their cancer treatment in that they now know that they are not alone; that their symptoms are now being recognized as a possible “side effect” of chemotherapy.

I find these reports fascinating in that the symptoms of “chemo-brain” are very similar to those that are associated with the earliest stages of conditions such as Alzheimer’s disease and “age-related cognitive decline.”  Research data regarding the actual mechanisms by which chemotherapy induces these symptoms will be of great interest to those investigating how the brain encodes and stores memory in a variety of conditions.

For More Information

“Chemobrain: the hunt for answers” is an article that appears in the online version of the American Psychological Association’s journal Monitor on Psychology.  The article is available at http://www.apa.org/monitor/apr05/chemobrain.html

The Mayo Clinic has published “Chemobrain: When cancer treatment disrupts your thinking and memory,” a well-written article with numerous links to related topics.  It is available online at

http://www.mayoclinic.com/health/cancer-treatment/CA00044

Notes

1. Janette Vardy, Sean Rourke, and Ian F. Tannock (2007): Evaluation of Cognitive Function Associated With Chemotherapy: A Review of Published Studies and Recommendations for Future Research, J Clin Oncol Jun 10 2007: 2455-2463.

2. Ian F. Tannock, Tim A. Ahles, Patricia A. Ganz, and Frits S. van Dam (2004): Cognitive Impairment Associated with Chemotherapy for Cancer: Report of a Workshop, J Clin Oncol Jun 1 2004: 2233-2239.

3. OA Selnes, MA Grega, LM Borowicz Jr,  S Barry, S Zeger, and McKhann GM (2004): Self-reported memory symptoms with coronary artery disease: a prospective study of CABG patients and nonsurgical controls, Cogn Behav Neurol. 17(3):148-56.

4. PV Raja, JA Blumenthal, and PM Doraiswamy (2004): Cognitive deficits following coronary artery bypass grafting: prevalence, prognosis, and therapeutic strategies, CNS Spectr. 9(10):763-72.

Clinical trials (also known as clinical investigation or medical research) ¹ are an important part of the process in which new drugs, treatment plans, or other such interventions are tested and validated under very strict medical supervision. Clinical trials are also known as investigational trials or as clinical research.

The purpose of a clinical trial is to evaluate whether some new drug or procedure is effective in preventing or treating a specific disease. As an example, suppose drug A shows promise as an effective treatment for high blood pressure but a diet rich in vitamin Z has also demonstrated the same effect. A clinical trial could be conducted to evaluate which of the two is the better treatment choice.

Clinical trials are comprised of various stages ranging from Stage 1 to Stage 4. The stages are described, in general terms, as follows. ²

Phase I: A new drug or treatment will be tested in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

Phase II: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.

Phase III: The drug or treatment is given to larger groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

Phase IV: Studies are done after the drug or treatment has been proven to be effective in order to gather information on the drug’s effect in various populations and any side effects associated with long-term use.

Any clinical trial, regardless of stage, will begin by defining both the inclusion and exclusion criteria of the study. These criteria will determine who will be eligible to participate (inclusion) in the study and who will not be eligible (exclusion). By way of example, suppose that a drug company wants to evaluate the effectiveness of a new treatment for lung cancer but does not wish to deprive anyone of a treatment (such as surgery, chemotherapy, or radiation) that has been shown to be effective in the past. The inclusion criteria might include patients that have not benefited from other forms of treatment, whose cancer has spread to other organs, and are not expected to survive beyond a few months. Obviously, anyone not meeting these criteria will be excluded from the study.

After a patient has met the requirements for inclusion in the clinical trial, the process cannot proceed until an informed consent has been obtained. Informed consent can be defined as furnishing each potential participant in the study with all the relevant information (such as potential complications, possible benefits, side effects from the investigational drug, and the probability of unforeseen complications) necessary for the potential study participant to make a decision as to whether or not to begin participation in the study. Only after these steps have been resolved will the participant enter (be enrolled in) the study.

Once the participant has entered the study he or she will be closely monitored for any unforeseen complications as well as those that can be reasonably expected to occur and were included in the informed consent process. It is important to remember that the participant always has the option to leave the study at any time. All investigational studies will also include an exit point (the point at which the investigational treatment has been completed and all the anticipated data has been obtained).

For More Information

Medical specialists such as neurologists and oncologists (doctors who specialize in the treatment of cancer) will be aware of various clinical trials related to their specialties and will share that information with their patients, if appropriate.

Clinical Trials.Gov: (US) This web site was created by both the National Institutes of Health and the National Library of Medicine and contains a more detailed discussion of clinical trials. It is easy to use, understand, and has numerous links to other related web sites.

The National Cancer Institute at the National Institutes of Health: (US) This site is devoted to the latest information on the prevention, diagnosis, and treatment of cancer. It contains a major database concerning both ongoing and proposed clinical trials at different locations across the nation.

Notes

1. “Clinical,” in the context of this posting, refers to medicine as it is practiced “at the bedside” or in an office / clinic.

2. Definitions adapted from those given by the National Institutes of Health and the National Library of Medicine.

Epilepsy is a neurological disease that affects an estimated 2 to 3 million people in the United States alone.  Despite continuing improvements in medical therapy, up to 40% of those with the condition continue to experience seizure activity while on 2 or more medications.  Additionally, although surgery for epilepsy has demonstrated dramatic improvement in some patients, it is considered to be too risky or not likely to be of benefit in the vast majority of patients.

California-based NeuroPace, Inc. is currently producing an implantable device that, it is hoped, will be able to detect the abnormal electrical pattern that develops within the brain prior to a seizure and to then administer a brief series of electrical pulses that will “abort” or “override” the abnormal activity and thus prevent a seizure from developing.

The device, which is known as a Responsive Neurostimulator System, has been cleared for use in clinical trials at 28 medical centers across the United States where up to 10 patients will have the device implanted outside their skull, with small wires inserted into the brain to monitor its electrical activity and to administer the electrical impulses.

NeuroPace points out that the device is not being evaluated as a “stand alone,” or single therapy, but as adjunctive (additional) therapy that will be used in addition to medication.

The study period is expected to last for anywhere from 2 to 3 years and will be limited to those 18 years of age or older that meet the additional medical requirements for participation in the clinical trial.

For More Information

See the NeuroPace home page for more details regarding topics mentioned elsewhere in this post.

Notes

Bergey, GB, et al (2002): Implementation of an external responsive neurostimulator system (eRNS) in patients with intractable epilepsy undergoing intracranial seizure monitoring. Epilepsia 43, Suppl. 7.

Tourette Syndrome is a neurological disease that is associated with muscular or vocal tics. ¹ More severe cases of this condition may be associated with self-abuse such as punching or slapping oneself or even the involuntary use of profanity (the action that many people associate with Tourette, but it is present in less than 5% of diagnosed Tourette Syndrome cases).

It has been reported that a significant percentage of Tourette cases will subside or even disappear in early adulthood. ²

Medical Management

Since the 1960s, the drug of choice in the management of Tourette Syndrome has been oral haloperidol (Haldol).  More recently, there have been reports of controlled studies reporting success using clonidine or Baclofen.

Treatment of Conditions Associated with Tourette Syndrome

Attention Deficit Disorder (ADD) and Obsessive Compulsive Disorder (OCD) are more commonly found in Tourette Syndrome than in the general population.  Whether there are common factors involved in all 3 conditions is unknown at this time.  Psychotherapy is the initial treatment of choice in ADD and OCD with medical management usually being reserved for those cases that do not respond to therapy. ³

Deep Brain Stimulation

Despite the occasional, but often sensational, reports concerning Deep Brain Stimulation (DBS) as a treatment for the most severe manifestations of Tourette Syndrome, there have been too few cases to determine whether DBS may become an accepted treatment for this condition. ^{4, 5}

“Alternative” and “Non-Traditional Therapy”

One thing that you can rely upon to hold true is that, regardless of the medical condition present, if a child is the victim of some medical condition there will be literally thousands of hucksters attempting to sell the parents some “alternative” or “miracle” treatment or even a “cure.”  Enter “treatment of Tourette syndrome” into your favorite search engine and you will find that it returns no less than 160,000 ‘hits.” 

I visited a number of these sites and was unable to locate a single reference to a report, in a reputable medical journal, which would support the claims made regarding such “miracle cures.”  In fact, most did not even bother to answer my e-mail requesting some supporting documentation regarding their respective products.  I would assume that they are not quite so hesitant in filling orders for their merchandise.

The plane and simple truth is that there are no miracle cures for Tourette Syndrome.  Save your time and money for more conventional therapies.

For More Information

The Tourette Syndrome Fact Sheet provided by the National Institute of Neurological Disorders and Stoke

Notes

1. A tic is an involuntary, repetitive contraction of a muscle group.  A vocal tic is a repetitive, involuntary noise such as clearing the throat, “snorting”, or some other  aphonal sound.

2. Bruun, RD and Budman CL (1997): The course and prognosis of Tourette syndrome. Neurol Clin 15(2): 291-8

3. Como, PG (1997): Tourette syndrome. Neuropsychological tests for obsessive-compulsive disorder and attention deficit hyperactivity disorder. Neurol Clin  15(2): 255-65.

4. Houeto, JL; Karachi, C; Mallet, L; B Pillon, and Yelnik, J (2005) Tourette’s syndrome and deep brain stimulation, Journal of Neurology Neurosurgery and Psychiatry 76:992-995

5. Neimat, Joseph (2006) Novel Surgical Therapies for Tourette Syndrome, Journal of Child Neurology, 21:8, 715-718.

While much of the published body of medical literature regarding Attention Deficit Hyperactivity Disorder (ADHD) is devoted to the diagnosis and treatment of ADHD in children, the burden of this condition in the adult population is only now being appreciated. 

There are 3 general categories of childhood and adult ADHD accepted by the American Psychiatric Association and included in Diagnostic and Statistical Manual of Mental Disorders (DSM), 4^th Edition:

1. ADHD, Combined Type
2. ADHD, Predominantly Inattentive
3. ADHD, Predominantly Hyperactive-Impulsive Type

Polanczyk et al ¹ estimate that the world-wide incidence of ADHD in all age groups may be as high as 5% while Silver ² and Wilens ³ estimate that as many as 70% of children diagnosed with this condition will continue to exhibit signs of ADHD into adulthood.  It should not come as a surprise that the behavioral difficulties associated with childhood ADHD are responsible for many social difficulties experienced by adults.  The more pronounced signs of adult ADHD include:

·         Unstable employment history

·         Easily becomes bored

·         Inattention to detail

·         Substance abuse including tobacco products, alcohol, and cocaine

·         Low self-esteem

·         Impulsive behaviors

·         Marital problems secondary to any of the above

As in children, the diagnosis of adult ADHD is quite subjective in nature and should thus be made only by clinicians with considerable experience in this field.  Generally, the diagnosis is based on the presence of 1) a history of ADHD as a child and 2) presence of specific signs and behaviors associated with ADHD that have been presence for a minimum of 6 months.

Adult ADHD, as in children with this condition, is most effectively treated by medication with any of a number of stimulants. ⁴ Additionally, adults with ADHD may benefit from psychotherapy with our without concurrent medical therapy.  Unlike childhood ADHD, the adult patient may require interventions to treat conditions known to be associated with ADHD such as substance abuse.

Resources

National Institute of Mental Health (2006): Attention Deficit Hyperactivity Disorder. Available online at http://www.nimh.nih.gov/publicat/adhd.cfm#adult

Notes

1. Polanczyk, G; de Lima, MS; Horta, BL; Biederman J, and Rohde, LA (2007): The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 164 (6): 942–948.

2. Silver, LB (2000): Attention-deficit hyperactivity disorder in adult life. Child and Adolescent Psychiatric Clinics of North America 9(3): 411-523.

3. Wilens, TE; Biederman, J, and Spencer, TJ (2002): Attention deficit/hyperactivity disorder across the lifespan. Annual Review of Medicine, 53:113-131.

4. Wender PH (1998): Pharmacotherapy of attention-deficit/hyperactivity in adults. Journal of Clinical Psychiatry, 59( 7):76-79.

In A User’s Guide to the Brain psychiatrist John Ratey offers a model of the human neuropsychological forces that give each individual their own “personality signature” and how a problem in one “upstream” area may not become obvious until it impacts another area “downstream.” 

This, of course, is certainly not a new observation in any sense.  One need only look to the works of Freud, William James, Jung, and others for confirmation of the importance of how the conscious mind is shaped by subconscious events and memories.

Ratey, however, discards the classic Id-Ego-Superego model in favor of a more holistically-oriented model which he describes as the “Four Theaters of the Mind.”

The Four Theaters

I.  The Theater of Perception

Ratey believes that a significant number of psychological problems are due to disorders of perception.  While it cannot be denied that perceptual difficulties are often a major contributor to disturbances in socialization or intellectual compromise, this writer feels that practically all disorders of perception can be attributed to alterations in either brain architecture or at the molecular level.

II. The Theater of Attention, Consciousness, and Cognition

It is indisputable that Theater II is probably the most interconnected and interdependent of Ratey’s theaters.  This interdependence is undoubtedly part of the reason behind the failure of analytic and behaviorist interventions in many psychological conditions.

III. The Theater of Brain Function

This theater is almost intuitive.  That structural and/or chemical change within the brain proper can be made manifest in disorders of personality and consciousness has been known since the days of Broca and Wernicke.  While many factors, such as brain injury or infection can affect the brain, much recent work in neurophysiology has been devoted to the belief that a genetic basis or a genetic predisposition is at the root of abnormal brain function.

IV. The Theater of Behavior and Identity

This theater is where individual identity and personality arise as a product of the other theaters.  Ratey gives two case studies demonstrating how disorders affecting perception, as an example, can adversely impact cognition which in turn could exert a strong influence on both behavior and identity.

This is not to say that I agree with Ratey on all topics. Since this writer is inclined to view mind and personality from a physicalist perspective (holding that the mind and personality do not exist independently of the brain), I would have listed Theater III as the first theater and Theater I as second.  Such disagreements are only trivial however, as Ratey’s concept is quite useful in understanding these topics.

Theory of Mind

Theory of Mind (TOM) is not a “theory” in the strictest sense, such as in Freud’s psychoanalytic theory.  Theory of Mind instead represents a completed stage of cognitive development (most authorities agree that this stage should be completed by age 11) that allows the child to understand and interpret their surroundings.

The concept of the theory of mind is an outgrowth of Jean Piaget’s work in the field of cognitive development in children.  Piaget held that an infant begins life with no idea of a world that exists beyond that which the infant can immediately understand via their own senses. As the infant matures he or she will learn that objects can exist, even though they may not visible, and to then anticipate future events.

It was first proposed in the early 1980s that children with autism seemed to have an incomplete or even arrested cognitive development, which would impair their ability to understand sensory input and to anticipate the responses of others.  This definition of the pathophysiologic disturbances most frequently encountered in the autism spectrum disorders seems to fit in quite well with Ratey’s Theaters of Mind model.

The above, of course, is only the briefest of introductions to what is a very complex subject.  Future postings on this site will address these issues in more detail.

Notes

Ratey, John:  A User’s Guide to the Brain. ISBN 0-375—70107-9 New York: Vintage (2002).

Leslie, A. M. Theory of mind impairment in autism, In A. Whiten, Ed., Natural theories of mind: Evolution, development, and simulation of everyday mindreading. Cambridge, MA: Basil Blackwell (1991)

Two interesting reports published have shed new light on the neurophysiology of the brain and, in one case, contributed to a better understanding of how the brain functions in addiction.

The first report, ¹ which appeared in the journal Science, involved a 28 year old man who had been a long-term (14 year) cigarette user until suffering a stroke that damaged a small part of his brain known as the insula.  This structure, which is roughly located just behind each ear and toward the center of the brain, has long been known to play a role in regulating the body’s conscious decisions regarding internal signals such as hunger.

Surprisingly, after his stroke the patient stopped smoking without withdrawal symptoms. “I simply ‘forgot’ to smoke” he stated to his physicians.  As of the date of the report, the urge to smoke has not returned.

Following discovery of the patient’s surprising outcome, investigators conducted a medical records review and identified a further 32 brain injury patients that had smoked prior to their injury.  Of these, 16 patients reported that they had ceased smoking without experiencing significant withdrawal symptoms.  MRI scans revealed damage to the insula in each of these 16 patients.

The second report ² is no less fascination than the first and is made even more remarkable in that it is a first-person account related by Ian McDonald, a British neurologist and amateur classical pianist, who suffered a “mild” stroke in 2004.

Initially, Dr. McDonald was unaware that he has suffered a stroke.  It was only after he began to experience difficulty performing tasks that had been routine that he sought attention from a fellow neurologist.  An MRI scan of the brain revealed that he had suffered a discreet (not widespread) stroke involving the right supramarginal and angular gyri which are, in turn, part of the brain’s parietal lobe.

Quite interestingly, the “routine” tasks that Dr. McDonald had experienced difficulty with were reading sheet music, playing even simple melodies, and being able to appreciate the subtleties of tone or timing of music being performed by others.

Fortunately, Dr. McDonald has made an almost complete recovery although he no longer plays piano in concert with other musicians..

These reports emphasize both the wide variety of consequences that may be present in brain injury as well as reminding us of the difficulties involved in research of human neurophysiology.  Since no physician or researcher can intentionally damage part of the human brain in order to study the consequences, it has been necessary to observe the changes in function that result from “natural” or “accidental” brain injury.  The above cases are illustrative of this strategy.

Another form of brain disease that has contributed volumes to neuro-medicine and neurophysiology is substance abuse and addiction, particularly in understanding the roles of various neurotransmitters in both health and disease.

Further developments along these lines of clinical research are eagerly awaited.

Additional Information

The National Institutes of Health and the National Institute of Drug Addiction publication The Brain: Using Neurobiology Through the Study of Addiction is written at the high school level and is probably the best online summary regarding the field of neurobiology that you will find.

The Dana Foundation publishes the online journal Cerebrum, a well-written and easily understandable summary of recent research and publications of interest.

Notes

1.  Naqvi, Nasir; Rudrauf, David; Damasio, Hanna, and Bechara, Antoine (2007)

Damage to the Insula Disrupts Addiction to Cigarette Smoking. Science 26 January 2007:
Vol. 315 (5811) pp. 531 – 534

2.  McDonald, I. (2006) Musical Alexia with Recovery: A Personal Account. Brain 129: 2554–2561.

Multiple Sclerosis (MS) is a degenerative disease of the central nervous system that is estimated to affect more than 400,000 Americans.  While the exact cause of MS has been widely thought to be a manifestation of some type of autoimmune reaction, current research indicates that, in addition to autoimmunity, several other factors may be involved in the disease process.  Such factors include a possible genetic predisposition to MS, exposure to some as yet unknown environmental toxins, and infection with viral organisms.

Current Treatments for MS

Since it is becoming clear that MS can be due to several different pathologies, it should be obvious that no single treatment is likely to work in all patients.  Currently, the US Food and Drug Administration has approved six therapeutic agent for the treatment of MS.  Of the six, four are considered to be “front line” agents and the remaining two are placed in the “second line.” category.

First-line drug therapies are those agents that are used once the diagnosis of MS has been made and are used to both limit the progression of the disease as well as alleviate symptoms that are currently present.  These agents are:

·         interferon beta-1b (Betaseron), administered as a once weekly subcutaneous  injection

·         interferon beta-1a (Avonex), administered as a once weekly intramuscular injection

·         interferon beta-1a (Rebif) , administered as a 3-times per week subcutaneous injection

·         glatiramer acetate (Copaxone), administered as a once daily subcutaneous injection.

Every first-line agent is known to produce a constellation of side effects which vary from patent to patient. The two most common of these side effects are 1) flu-like symptoms ranging from mild to incapacitating and 2) pain and tissue destruction at injection sites.

Second-line therapies are generally used as “treatments of last resort”.  This is because, unlike the interferons or glatiramer acetate, these agents directly suppress the body’s immune system and may limit the body’s ability to protect itself against infection.  The approved second line agents are:

·         mitoxantrone (Novantrone) administered intravenously

·         natalizumab (Tysabri), also administered intravenously

Emerging Treatments for MS

There are several potential pharmaceutical treatments for MS that are in the later stages of clinical trials.  These agents include:

·         Fingolimod:  This agent was initially developed as an anti-rejection drug for use in organ transplant recipients but was proved unsuccessful during clinical trials. A subsequent clinical trial in MS patients not on other therapies demonstrated that fingolimod reduced the accumulation of MS-specific lesions on MRI by 43% to 61% relative to placebo and was associated with clinical improvement in over 50% of those participating in the study.

 Fingolimod is currently undergoing extended clinical trials, with the first results due in 2008.

·         Fumarate:  Fumarate is derived from the plant Fumaria officinalis, which has been used to treat skin diseases such as eczema since at least the 17^th century, has been shown to inhibit the immune system.   Initial phase 3 trials have shown that fumarate produced 69% reduction in MS-specific lesions on MRI. This initial study did not examine clinical improvements in the study population.

 Fumarate is now in extended phase 3 trials.

For More Information

The most reliable online sources for information about MS and treatment strategies is the National Institute of Neurological Diseases and Stroke’s Multiple Sclerosis Information Page.

As always, the information presented above is of an informational nature only and is not a substitute for consultations with your health care provider.