Effective Treatment Leads to Better Brain Function

The hippocampus in the center of your brain plays a vital role in memory and learning, reducing pain, and controlling (often dampening) your body’s response to stress. Given that fibromyalgia patients have cognitive difficulties, severe pain, and a hyperactive stress response, clinician and researcher Patrick Wood, M.D., hypothesized in 2003 that this brain area would show chemical and structural abnormalities that corresponded to the symptoms. Funded by the American Fibromyalgia Syndrome Association (AFSA), Wood’s project has led to the publication of three exceptional reports that illuminate what is happening in the brains of people with fibro.

Initially, Wood demonstrated that an important metabolite (NAA/Cr) was abnormally low in the hippocampus and was related to the severity of the fibromyalgia patients’ symptoms.¹ N-acetylasparate (NAA) represents how effectively your neurons are functioning and creatine (Cr) represents the amount of energy consumed. Computing the ratio of NAA to Cr is thought to help standardize individual results for more accurate comparisons. See the September 30, 2008 posting in our Latest News section for additional study info and what the results might mean for you.

Next, Wood showed that fibromyalgia patients had reduced gray matter in the hippocampus and it appears to be related to a loss of dopamine activity in this region.² Hippocampal dopamine plays a strong role in the pain inhibitory system, so a drop in activity could help explain why fibromyalgia patients have pain all over.

Although loss of gray matter can sound scarey, it appears to be reversible. Wood’s most recent article offers proof that the brain imaging findings in the hippocampus are directly tied to the symptoms of fibromyalgia (at least in some people) and can be reversed with the proper therapy.³ According to a patient case report, a 47-year-old woman who exhibited an abnormally low NAA/Cr ratio was successfully treated by Wood. A follow-up image taken of her brain scan showed that the NAA/Cr value increased to normal.

Wood offers a detailed picture of a woman who was diagnosed by two different rheumatologists as having fibromyalgia before entering his study. After an automobile whiplash accident she reported symptoms of widespread pain, diffuse tenderness, disturbed sleep, severe fatigue, numbness and tingling sensations, frequent headaches, constipation-related irritable bowel syndrome, cold-sensitive extremities, and difficulty with concentration and short-term memory. No doubt these latter symptoms of fibro fog were very distressing given that she was employed as psychotherapist with a Ph.D. She also reported being premenopausal with irregular menstrual cycles, heavy bleeding, cramps, and premenstrual irritability.

On the first visit, her Fibromyalgia Impact Questionnaire (FIQ) score was 52 on a scale from 0 to 80, where 80 is the worst possible score. In addition, she had the following symptom scores on a scale from 0 to 10 (10 being the worst possible):

pain = 5.5
fatigue = 10
symptoms at rest = 10
stiffness = 8.5

The above scores all indicate a patient who is very significantly impacted by her fibromyalgia symptoms, but she was not depressed. Due to her menstrual symptoms, Wood tested her hormone levels and found that her estradiol (e.g., estrogen) was extremely elevated. Otherwise, her blood work was normal.

After agreeing to participate in the brain imaging study, her hippocampal NAA/Cr ratio was found to be very low at 1.07 (normal is around 1.34). Wood repeated the scan and the results were the same. Oddly, her Cr level was slightly elevated, which may have been a contributing factor to her low NAA/Cr ratio.

Soon after completing the study, she sought Wood’s help in treating her fibromyalgia. Her pre-study symptom scores can be used as a baseline or basis for comparison.

Treatment Visit #1: Nighttime sympathetic nervous system hyperactivity may have interfered with her ability to sleep and the concept that beta-adrenergic receptors in the hippocampus could be bombarded with signals from the sympathetic system. So a beta-adrenergic receptor blocker was prescribed at bedtime (60 mg of long-acting propranolol or Inderal-LA). Wood speculated that her high estradiol level was causing central nervous system hyperactivity, which contributed to her menstrual symptoms and disrupted sleep (including next-day fatigue). He recommended that she take the over-the-counter supplement, indole-3-carbinol, to increase the speed at which the liver breaks down estrogen for excretion in the urine. In addition, he balanced the remaining estrogen with a prescription for natural progesterone at bedtime on days 12 through 26 of her cycle (formulated in slow-release 200 mg capsules at a compounding pharmacy).

Treatment Visit #2: After 10 weeks, she returned with a much improved FIQ score of 30 (it was 52 at the beginning). She reported less pain at rest, improved sleep, and much more energy. However, she still had residual menstrual cycle symptoms and trouble sleeping. Wood increased her nighttime progesterone to 300 mg for the second half of her cycle and placed her on a small nightly dose of Ambien (zolpidem 5 mg) to help her sleep.

Treatment Visit #3: At her 16-week follow-up, her FIQ was down to 19. She reported continued improvement in all symptom areas, so the decision was made to stick with the same therapies.

Treatment Visit #4: At her 28-week follow-up with Wood, her FIQ score was down to 8 and she reported being “essentially pain free.” Her primary concern was constipation, dry mouth, and fatigue following exertion. He prescribed pyridostigmine, which works to increase the activity of acetylcholine, the main communication transmitter used by the parasympathetic nervous system (the one that helps with “rest and digest”). The drug’s side effects of increased GI motility and saliva/tear production were thought to relieve her remaining symptoms. Indeed, the patient described this last addition to her therapy as the “crowning touch” in her complex, symptom-based regimen.

Treatment Visit #5: A few weeks after the fourth visit, Wood conducted a telephone follow-up consultation with the patient. She was virtually symptom free while remaining on the prescribed therapies. In addition to her full-time job, she had enrolled in a rigorous postgraduate certification program in her field. Wood asked to take another brain scan to look for evidence of change. Her NAA/Cr ratio increased to 1.34 (it had been 1.07) and the average for the healthy control group was also 1.34. During this follow-up brain scan the value of Cr dropped. This appears to be why the NAA/Cr increased to normal (at least in this particular patient).

“It is tempting to speculate that the clinical improvements experienced by this patient might be related to decreased hippocampal energy metabolism,” writes Wood. In other words, by applying therapies that reduce the excitability or amount of activity in the hippocampus, the result should be a decrease in energy use (e.g., lower Cr values). This should also enable the hippocampus to recover from being overworked and to begin focusing on vital functions such as memory/concentration, pain control, and regulating the stress response system. With these processes operating optimally, the symptoms of fibromyalgia should improve.

While the regimen prescribed for this 47-year-old fibromyalgia patient successfully eliminated her specific symptoms and reversed her NAA/Cr hippocampal metabolite abnormality, keep in mind that each person with this condition is different. The key for treating physicians is to use strategies aimed at correcting the physiologic abnormalities associated with the disorder. In this particular case, the patient had hormonal imbalances associated with her menstrual cycle, symptoms suggesting a hyperactive sympathetic and underactive parasympathetic nervous system, and disrupted hippocampal functioning. All of these factors likely contributed to her pain, brain fog, sleep disorder, daytime exhaustion, and GI symptoms to varying degrees.

“Given the multiple interventions detailed herein,” writes Wood, “it is admittedly difficult to parse out which specific agent may have contributed the greatest impact on the combined improvements. However, on the basis of this experience, therapeutic strategies aimed at demonstrable lesions associated with this unusual disorder seem to represent rational targets for pharmacologic interventions that warrant further investigation.” In other words, more research on the hippocampus in fibromyalgia could lead to better treatments.

Other therapies that Wood often recommends to help restore the “health” of the hippocampus include omega-3 fish oils (especially EPA and DHA), acetyl-l-carnitine, and dopamine-like drugs (agonists such as Mirapex or Requip). The research for these three related reports was conducted while Wood was at Louisiana State University in Shreveport. He is now in private practice near Seattle, WA, with Andrew J. Holman, M.D. Wood’s clinic is devoted entirely to the care of patients with fibromyalgia, and this case report emphasizes that patients with more forward-thinking doctors may have milder symptoms. In other words, the medications are important, but the skill with which your doctor uses them is equally important.

1. Wood PB, et al. J Pain 10(1):47-52, 2009.
2. Wood PB, et al. J Pain 10(6):609-18, 2009.
3. Wood PB, et al. Clin J Pain 25(9):810-4, 2009.