Migraine Headaches – Rethinking an Old Malady

Neuroscience_Neurology2.jpgPhysicians must choose among numerous treatment options for pain. Many pain syndromes would benefit from more effective approaches. Migraine headaches are a prime example of a painful condition in need of a better solution. Recent insights provided by research investigating the mechanisms causing migraines are beginning to generate new approaches to an old problem.

In addition to producing throbbing (usually unilateral) head pain, a migraine attack is often accompanied by nausea, vomiting, sensitivity to light, tenderness over the scalp, and at times a strange visual disturbance called an aura that precedes the headache by about thirty minutes.

Understanding the cause of migraine headache and aura symptoms has proven to be a daunting task. Since the brain feels no pain, the discomfort that accompanies a migraine is believed to arise from both the blood vessels in the brain and the coatings of the brain, called the meninges. For many years, the so-called vascular theory of migraine directed pharmaceutical approaches. It was believed that aura symptoms were due to constriction of blood vessels in the back part of the brain, which then produced diminished blood flow, reduced oxygen supply, and subsequently generated the characteristic visual symptoms of flashing, shimmering lights that move across the visual field. The subsequent headache component was felt to be related to dilation of meningeal blood vessels with an associated release of inflammatory chemicals over their surface.

More recently, attention has shifted from a vascular theory to a neural theory of migraine causation. What acts as the ultimate trigger is unknown, but it appears to be located in the cerebral cortex – the convoluted surface of the brain. There may even be multiple cortical regions that contribute. It is postulated that some perturbing event in the surface of the brain is the culprit, which is followed shortly thereafter by a depolarization (or firing) of surrounding brain tissue that creates an expanding ripple like the rings on a pond when a stone breaks the surface. This expanding wave of depolarization is referred to as cortical spreading depression (CSD). Some researchers believe this helps explain the migraine aura, especially when CSD develops in the visual cortex.

Evidence from a rare type of headache called familial hemiplegic migraine, because of the development of one-sided weakness concurrent with the headache, has provided insight into possible triggers for the wave of CSD. Genetic mutations that result in malfunction of specific ion channels in nerve cells have been identified in this headache variant. When these ion channels undergo periods of decreased function, sodium, potassium and other ions build up where they don’t belong, making the nerve cells irritable and more likely to fire uncontrollably. Such unregulated depolarization (firing) is energetically expensive and results in accumulation of the excitatory neurotransmitter glutamate. This initiates a metabolic cycle that further stimulates nearby neurons, thus creating increased energy demands. As available cellular energy supplies fall, glutamate continues to increase and the cycle intensifies.

This process is reminiscent of what occurs when seizures are triggered. It just so happens that CSD can be suppressed by the continuous use of a wide array of anti-seizure medications. These drugs are effective not only for migraines with aura, but also for migraines without aura. This suggests the possibility that CSD may or may not cause visual auras (presumably when it doesn’t involve the visual cortex).

It seems that by alleviating the ionic imbalance that triggers the wave of CSD, these medications suppress migraine development. By decreasing cortical excitability they also suppress the “hyperexcitability-energy depletion cycle” that ensues. In addition to pharmaceuticals, non-prescription approaches that might achieve the same results can be envisioned. A report by a physician whose wife suffered from persistent migraines revealed a serendipitous result. Apparently the woman went on a reduced calorie diet consisting of low-carbohydrate protein shakes to lose weight after two pregnancies. Not only did she lose the desired weight, she also “lost” her migraine headaches. They didn’t return even when she assumed a more conventional diet.

The relationship between her physiologically induced ketotic state and migraine cessation is reminiscent of the use of ketogenic diets for epilepsy. If the current evidence identifying cortical instability as the inciting stimulus for CSD holds, both triggers (seizures and migraines) involve foci of irritable cortex and would be expected to respond similarly to therapeutic intervention. However, rather than suggest that a person change to a ketogenic diet, it might make more sense to recommend a trial of MCT oil (medium chain triglyceride oil) for migraine suppression. MCT oil is rapidly metabolized by the liver into ketone bodies that are delivered to the brain. Just as occurs during ketogenic dieting, ketone bodies would be expected to beneficially affect the glutamate/GABA balance of neurotransmitters while simultaneously improving the neuronal energy charge. These would act to diminish neuronal excitability and suppress CSD. If this occurs, and it seems likely based on the anecdotal report of the doctor’s wife, MCT oil may prove to be a novel alternative to drug induced prophylaxis for migraine prevention.

Larry McCleary, M.D., is the former acting Chief of Pediatric Neurosurgery at Denver Children’s Hospital, the author of The Brain Trust Program: A Scientifically Based Three-Part Plan to Improve Memory, Elevate Mood, Enhance Attention, Alleviate Migraine and Menopausal Symptoms, and Boost Mental Energy, and maintains his own blog at www.drmccleary.com.

Larry McCleary, MD

Larry McCleary, MD, is the former acting Chief of Pediatric Neurosurgery at Denver Children's Hospital. He is trained and has practiced as a pediatric neurosurgeon and has completed post-graduate training in theoretical physics. His scientific publications span the fields of metabolic medicine, tumor immunology, biotechnology and neurological disease. He has lectured to audiences around the world. He is the author of Feed Your Brain Lose Your Belly (Greenleaf Book Group, 4/1/11).
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