When I reviewed Chronic Fatigue Syndromes: The Limbic Hypothesis, in the ASAP Forum Journal (December 1995) after meeting Dr. Jay Goldstein at a continuing education medical presentation in Tuscaloosa, Alabama, I was convinced that his work might be of some importance in explaining the many non-GI symptoms that I have seen both with my wife, Leah, and the many other patients that I have met with the diagnosis of Chronic Intestinal Pseudo-Obstruction (CIP). Although we finally made our way to the sub-specialty clinic that yielded Leah's diagnosis in about two years of searching, we were still unable to find any explanation for these many concurrent symptoms. Neurologists, Endocrinologists, Infectious Disease Specialists, more Neurologists--none could venture a theory as to how a disease of the gut could cause orthostatic hypotension (fainting or dizziness on rising), headaches, fatigue, diffuse pain, confusion and forgetfulness (I have met patients who got lost in their own kitchen), Raynaud's Syndrome, photophobia, seizures, and the dozen or so other complications so frequently associated with the disease. Some vague mentions of the same neurotransmitters and peptides being present in the brain as well as the gut, and the ever-present mystery of the vagal nerve were tossed about with no further insight (by the way, 90% of the fibers of the vagal nerve are afferent--inputs to the brain). Yet most research into CIP is primarily GI oriented.
Dr. Goldstein's The Limbic Hypothesis was the first of the hundreds of references that I have searched that offered a convincing model for this phenomenon. In Betrayal by the Brain, he expands and updates his theory with new insight and current developments that are even more compelling, as well as presenting a refined treatment protocol that is effective in 90% of his patients.
Betrayal by the Brain, is a continuation of Dr. Jay Goldstein's evolving hypothesis that Chronic Fatigue Syndrome (CFS), Fibromyalgia (FMS), Gulf War Syndrome, and dozens of other illnesses that he defines as neurosomatic, are disorders of the management of sensory input by the brain as a result of an interaction of genetic, developmental, and environmental factors. He explains the pathophysiology of these diseases in ways that amount to a new conceptualization of the mechanisms of health and illness. Dr. Goldstein attempts to bridge the gap between the basic researchers and clinicians by bringing together cutting-edge knowledge from neuroscience, rheumatology, gastroenterology, endocrinology, psychiatry, and pain researchers.
After a brief introduction in which he explains the concept of neurosomatic illness and its causes and the difficulties in gaining acceptance in the medical arena, he devotes lengthy chapters to in-depth discussions of Fibromyalgia Syndrome and the Pathophysiology of Chronic Fatigue Syndrome. These are complex medical issues and involve explanations of neural structure and neurotransmitter action. He expands his earlier theory of limbic dysfunction from the prior book, The Limbic Hypothesis, to show that the limbic control, while responsible for most symptomatology, is modulated by other brain structures, the most important being the prefrontal cortex, with its dysfunction then causing the abnormalities of limbic regulation. So while neurosomatic illness is due to limbic action, drug therapies that affect other areas of the brain can remediate the somatic (body) manifestation. A chapter on the Cerebellum and Basal Ganglia illustrates the only very recent appreciation that the basal ganglia, besides being involved in motor functions, also processes somatosensory information and encodes stimulus intensity, but not location. The receptive fields of these neurons may include the entire body and may be perhaps the most important brain structure for nociception (perception of pain).
A chapter is devoted to Irritable Bowel Syndrome in which he debates the "bottom up" approach in which symptoms originate in the GI tract and produce central changes, versus his "top down” ideas fortified by SPECT brain imaging and more importantly, global symptom response to his treatment protocol. SPECT (single photon emission computerized tomography) measures the blood flow in the brain and presents it as a colored computer image with the different colors indicating the amount of blood flow in the various regions of the brain. Normal brains display a more uniform pattern of blood flow, but CFS patients generally show abnormal and distinctive hypoperfusion (lessening) patterns which means that those areas of the brain are dysfunctional, although no abnormalities will show up on CAT or MRI, which show only structure (the problem appears to be with regulation of receptors, and probably post-receptor messengers). An MRI cannot distinguish between a living brain or a dead one. Functional Bowel Disease (FBD) has been found to occur in 72% of patients with CFS. When he compared the regional cerebral blood flow (rCBF) as measured by SPECT scan between CFS patients with and without FBD, there was no difference in rCBF except that the FBD-positive patients had more severe hypoperfusion than those who were FBD-negative.
A final chapter is devoted to the treatment protocol that he uses with his patients in which he discusses each drug and its mode of action in detail. It is curious that some of the drugs used in his protocol do not cross the blood-brain barrier and yet still have marked effects on CNS function. Apparently the brain can be modulated by molecules acting at the level of peripheral nerves and autonomic ganglia. Another strange observation is that while some of the drugs from his protocol are vasodilators, such as nitroglycerine (which you would expect to use if you were treating a condition of hypoperfusion), all of the drugs that result in rapid and profound relief of symptoms cause decreased rCBF when the treated brain is re-examined by SPECT. One would expect that a disease state indicated by hypoperfusion, would be worsened by a drug that produced further hypoperfusion, but this is not the case. The further reduction of the rCBF seems to be an epiphenomenon of the drug action, and some drug's effect is to stimulate the release of norepinephrine which triggers the secretion of corticotropin-releasing hormone (CRH). Some drugs also decrease substance P and others enhance neural plasticity by increasing the secretion of glutamate.
This book, while still a complicated medical text, is much more "reader-friendly" than its predecessor. A list of abbreviations of the hundred or so medical terms repeatedly referred to throughout the book is conveniently placed at the very beginning. The voluminous (over 70 pages!) and very current (1996) listing of references is placed at the end of the book instead of at the end of each chapter, making it much easier to find sources of interest and simplifying the footnoting for the entire text. Physicians should find this volume essential for its compilation of references alone.
But perhaps as important (maybe more-so for the patient) is the inclusion of frequent and numerous case reports. These serve quite clearly to show how patients with CFS and other neurosomatic disorders (IBS, PMS, etc.) do not all respond to any one treatment, and dramatically illustrate the sometimes miraculous response by rapid remediation of symptoms during the office drug trials. Patients who have been sick for twenty years can feel normal in a few minutes, and patients who have not responded to a trial of fifty medications can feel better with the fifty-first. Patients whose symptoms wax and wane seem to have the rapid response, while those with more chronic symptoms may improve with other drugs. Dr. Goldstein points out that his therapies are pharmacologically driven, not symptom driven, and that, “Treating neurosomatic disorders seems to be a matter of pushing the right neurochemical buttons.”
Although I found this book easier to read than The Limbic Hypothesis, it may still be difficult for the lay person (although I recommend it highly if you read it only for the many case reports). For this very reason, a patient of Dr. Goldstein's, Katie Courmel, has written A Companion Volume to Dr. Jay A. Goldstein's Betrayal by the Brain: A Guide for Patients and Their Physicians. She was a software development manager until 1992 when an injury developed into fibromyalgia and CFS. After developing frequent daily seizures and being told that they were psychosomatic by Neurologists, she wrote to many FMS/CFS researchers and Dr. Goldstein is the only one that responded.
She spent a week in his clinic and experienced the entire protocol only to prove to be one of the 5% of his patients that do not respond well. However, she saw daily miracles while waiting in his office, and he continues to work with her for the proper medication that will be successful for her. She is convinced that his work is too important to not be accessible to the lay reader and for that reason has tried to simplify the terminology without sacrificing the body of information that allows one to understand these disorders. This shorter volume describes all of the pertinent regions of the brain and their dysfunction as well as the drug remediation. Neurochemical transmitter substances are defined and their normal and dysfunctional actions described. A drug protocol reference table lists their normal usage, mode of action, effect on patients, possible side effects, and onset and duration of action.
Since many physicians are reluctant to attempt the Goldstein protocol even when they subscribe to his theory, this outline of his evaluation, treatment, and follow-up should encourage them to participate in this exciting new approach to a set of illnesses that are often untreatable in other ways.
Leah recently had the brain SPECT done (mid-nineties) with exactly the results predicted by Dr. Goldstein--hypoperfusion of the prefrontal cortex and the temporal lobes. This was shown as a baseline SPECT scan and was followed by another SPECT on the next day in which she was asked to smell ammonia. The ammonia challenge is interpreted by the brain as danger—“the lion is coming to the picnic”—and the SPECT then showed intense activity of the basal ganglia. It's interesting to note that the limbic system is located in an area of the brain not completely protected by the blood-brain barrier and would be more vulnerable to whatever toxic or infectious biological insults that may also affect the gut.
Some CIP researchers have performed full thickness biopsies of the small intestine and discovered an infiltration of lymphocytes in the tissues that may suggest an autoimmune disease. A blood test called the Western Blot has been used to show numerous auto-antibodies in the sera of some persons with pseudo-obstruction (PWPs) and it is thought that this may indicate an autoimmune process as well. Often these auto-antibodies clear from the sera with Lupron therapy.
One of Dr. Goldstein's case reports describes a female with a 17-year history of systemic lupus erythematosus (SLE), a well known autoimmune disease. She had positive antibodies for double-stranded DNA and a recent biopsy consistent with Sjogren syndrome. She developed CFS and responded well to Dr. Goldstein's therapy. What is interesting here is that over the first three months of treatment, all signs of the lupus resolved and her anti-ds DNA test became negative. Since it is a basic principle of psychoneuroimmunology that postganglionic noradrenergic fibers of the autonomic nervous system regulate the function of the spleen and lymph nodes and even individual immunocytes, it seems reasonable to assume that a neurosomatic treatment protocol could ameliorate autoimmune disease. Since all of the Goldstein protocol drugs are relatively free of adverse reactions and do not appreciably interact with one another, it would seem that this would be an area of great interest for those research physicians in this arena.
Betrayal by the Brain by Dr. Jay Goldstein is available in softback for $29.95 and hardback for $49.95. A Companion Volume to Dr. Jay A. Goldstein's Betrayal by the Brain by Katie Courmel is available for $14.95 in softback only. Either may be ordered by calling The Haworth Medical Press at 1-800-342-9678.
A videotape of Dr. Goldstein's lecture to a patient group can be obtained for $20.00 (postage included) from: Tuscaloosa CFS Support Group, c/o Janice Bryant Kunz, 1617 11th Street, Tuscaloosa, AL 35401. Checks should be made to Janice Bryant Kunz; please allow 3-4 weeks for delivery since both Janice and her child have CFS.
Teaching faculty can obtain an examination copy of Betrayal by the Brain and the earlier Chronic Fatigue Syndromes: The Limbic Hypothesis (now $39.95 hard; $19.95 soft) on 60-day examination basis. You will receive an invoice payable within 60 days. If you decide to adopt the book, your invoice will be canceled.