Thursday, July 28, 2011


At 19 years of age, a young woman presented with a typical case of juvenile rheumatoid arthritis that began with “muscle spasms” in 2008 when she was a member of the high school swim team. Then more and more joints became painful and swollen and the diagnosis became clear. In March of 2011 she had had both knees drained of fluid. Her treatment had been the usual and customary. All the drugs were aimed at attempts to block inflammation.

It is only by looking at the life time history and the 2011 physical examination that this could be seen as clearly related to the brain/body interplay. A pediatrician always goes back to the birth history and asks questions whose answers have long been forgotten and thought to be past history of no consequence. She had jaundice at birth but did not receive the conventional blue light treatment. Further history revealed that she had become dehydrated in the first few days of life and required intravenous fluids. Pink crystals were reported to have been found in her urine and these are known to be from uric acid that has crystallized out. Uric acid is a metabolite of purine metabolism and is not normally found in urine in enough quantity to crystallize. It is therefore a signature of an abnormal state of metabolism. She remained jaundiced for at least a month and was known by the family as “a yellow baby”. She was also said to be “unusually sleepy” for the first few months of life. We now know that the relatively common neonatal jaundice has been published as the first evidence of oxidative stress. There was clearly a biochemical problem existing at birth. At the age of 6 years she had a series of acute attacks of asthma. In 2007-8 she had a long series of upper respiratory infections where it was difficult to see when one ended and another began. By this time she was an excellent student and was, as mentioned, on the high school swim team when the history of muscle spasms and joint inflammation began.

A physical examination in June 2011 revealed the expected facial pallor, the usual signature of chronic illness, together with the swollen and painful joints. There were, however, some other signs that are seldom recognized for what they represent. Her tongue looked superficially like the surface of a raspberry, so it is referred to as “raspberry tongue”. In my experience, this is usually related to the quality of diet. More importantly, she had no evidence of knee reflexes induced by the customary rubber hammer used by physicians. This was further tested by what is called “reinforcement”. The patient was asked to clasp her hands together and give a quick pull on request. As the rubber hammer descended to elicit the reflex she was given the sharp request to “pull”. Without further explanation, this usually will enable the knee jerk to react. There was still only a tiny flicker of the reflex. By gently stroking the leg with a finger tip, I was able to cause a white stripe to appear slowly in the wake of the finger stroke. This is known as “dermographia” or “skin writing” and it is an easy way to detect that the control mechanisms of the autonomic nervous system are functioning abnormally.

Without complicating this further, these simply elicited phenomena in the examination of the legs clearly indicated that the “command center” in the limbic brain was involved. We have now much evidence in the medical literature that inflammation and immune responses in the body are initiated from the lower brain. The body/brain communication is a new way of thinking about disease in general (Blalock J E. The immune system as sixth sense. J Internal Medicine 2005;257:126-138.) To call it a “command center” is no exaggeration. This part of the brain has a high demand for efficient metabolism depending on rapid consumption of oxygen. It consumes huge amounts of available energy and works 24 hours a day throughout life as does the heart. That is why the vitamin B1 deficiency disease, beriberi, affects the heart and brain, because vitamin B1 is a major catalyst in the oxidation mechanisms that process glucose to synthesize adenosine triphosphate (ATP), the “currency” of energy chemistry. Thus, in this case, the history showed that metabolic efficiency was compromised even at birth and culminated eventually in unwanted signals from the control centers in the brain to initiate inflammation in excess.

How can all of this be fitted together to make sense that the brain and body are but two parts of the same “machine”? There is no mental illness without an effect in the body and no physical body disease without brain involvement. We can think of the body as being like an old fashioned fortress. The “soldiers” that act as defensive agents are the white cells that are sent to the appropriate area where an attack is being recognized by the “command center”, alerted by reflex input from the area under attack. This results in inflammation and is a normal defensive response. If, however, the command center is out of order, an inflammatory response might be haphazardly ordered in excess and we then see what we recognize as inflammatory disease. It is the Yin and Yang again--- not too little and not too much. There must be an appropriate and balanced command. By doing a library search, I was able to find plenty of evidence that the limbic brain (“command center”) becomes much more responsive to incoming information supplied by the sensory system if its oxidative metabolism is compromised. All brain function is tied to this and it goes a long way to explain why a high IQ increases risk and why the “command center” gets into the picture. An intelligent, athletic, active individual like this patient has a greater demand for efficient oxidative metabolism compared with a less gifted person. With mild to moderate loss of this efficiency the control centers become more reactive to incoming sensory signals that demand an adaptive response. The executive signals may be through a normal neurological system but they are exaggerated and cause too much organ reaction.

The point is this: the brain has to recognize our defensive capabilities to protect us and enable us to adapt to all physical and mental stress factors that we meet on a daily basis throughout life. It is equipped with a large number of complex reflexes that enable us to survive in a hostile environment. The fight-or-flight reflex is the one that most people are aware of. Inflammation is an obvious defensive reaction to injury and if the brain does not initiate it when it is required, we will not be able to repair the injury (Yin). If, on the other hand, it initiates unwanted inflammation because of confusion in the brain/body signaling mechanisms, there is unwanted inflammation in target organs (Yang). It is not clear why a particular organ or set of organs (e.g. joints) would be targeted. It may be somewhat haphazard or it may be directed because of the particular nature of the individual genome that provides the risk. It must be emphasized however that it is genetic risk, not a specifically genetically determined disease. Epigenetics is the new science of studying how we affect our genes by diet and lifestyle. By far and away the easiest way to induce this brain/body reaction is to ingest empty calories, particularly those from simple carbohydrates.

Since this concept depends on the ability of cells to meet their energy demands, it means that the best and the brightest are more at risk than those with lesser endowments. This concept would perhaps explain the early death of Mozart, the nature of his death having been argued over the years. He simply ran out of the energy currency in its accelerated consumption.

It is an ancient aphorism that “complexity has to give rise to simple solutions to be efficiently effective”. Modern research is discovering more and more detail about the brain/body messenger systems (Oke S L, Tracey K J. The inflammatory reflex and the role of complementary and alternative medical therapies.Ann. N.Y Acad Sci 2009;1172:172-180). The details are so complex that a reader has to have special knowledge to understand the technical terms. One of the conclusions drawn by the authors, however, is that elucidation of this inflammatory reflex has enabled investigation into drugs, therapeutic techniques such as electrical stimulation, and even complementary and alternative medical therapies. The reflex is mediated through the vagus nerve that goes from the brain to many internal organs and they found evidence that acupuncture can increase the action of this nerve.

It is fascinating that healing by stimulation of this nerve has been used by Yogis for centuries and they have advocated several methods that seem to most of us like “mumbo jumbo”. Perhaps the mechanisms were not known and it is amazing that such methods were developed without this knowledge. Acupuncture has been used for at least five thousand years and it may be even older than that.

It seems to me that we must look at the brain/body as an extremely complex “machine” that, for most of us, is complete and works automatically to enable our survival as individuals and as a species. It may be exciting to know the infinity of details but all it requires is energy to drive it. I must emphasize that I am talking about the energy used for cellular function, not the colloquial use of the word in describing a person’s athletic ability. We have to remind ourselves, that is the use of energy. We have to generate that energy in order to transduce it into function. Hippocrates, the “Father of Modern Medicine” said “Let medicine be your food and food be your medicine”. This encapsulated wisdom has been largely ignored and we should be looking hard at other forms of ancient wisdom, rather than the commonly held idea that the ancients were all “left behind” by our modern technology. Perhaps the “Father” is ignored in the same way that our modern era has reduced the impact of parental wisdom on their offspring.

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