Jennifer Green, MS – Brain Blogger Health and Science Blog Covering Brain Topics Wed, 30 May 2018 15:00:03 +0000 en-US hourly 1 When “Alternative” Isn’t Anymore – The Ketogenic Diet in Epilepsy Sat, 06 Sep 2008 04:06:39 +0000 I hang out sometimes on a forum for parents of children with epilepsy. It’s a heartbreaking place. If there are kids whose seizures are controlled by medication and who are doing well — or even making it through the day — in school, their parents are posting somewhere else.

The forum’s purpose is to let parents know about ‘alternative’ treatments for epilepsy. We’re not talking about flower essences, mega doses of vitamins, or Reiki, either. The treatment that parents tell each other about most often is the ketogenic diet — and its cousins, the modified Atkins, low glycemic index, and specific carbohydrate diets.

The ketogenic diet has been tested repeatedly — including a recent RCT that demonstrated its efficacy at helping children with intractable seizures despite multiple medications. But, as far as I can tell, most parents still learn about it from each other, not their physicians.

Complex Partial SeizureMost of the kids I know about from this site have multiple types of seizures, and they’re on at least two, and commonly three, anti-epilepsy drugs. These drugs have significant side effects, and more than one parent believes that their child’s medications have increased the frequency of seizures, brought about a new type of seizure (myoclonic or drop seizures, for instance, in a child with absence seizures), or caused developmental delays.

The ketogenic diet induces long-term ketosis, a condition in which the body converts fat into energy instead of carbohydrates, by extreme dietary modifications. The mechanism behind its effectiveness might be an increase in leptin. This has only been demonstrated in animal studies so far, but the parents on the forum don’t really care why it works. They only care that it does.

Reponses to the ketogenic diet can sometimes be dramatic. One mother posting on the forum indicated that her son went from having roughly 90 seizures a day to none within three weeks. Sometimes, it takes longer to work, and, in some children, it helps to a minimal degree. It’s not without risks, but its effect can be nothing short of miraculous.

Most epileptologists are well aware of the diet’s potential to help children who are otherwise trapped in a body that’s out of their control. But many other physicians aren’t, even though prominent specialists recommend that the ketogenic diet should be second-line or even first-line treatment for certain types of seizure disorders.

If ever there was an ‘alternative’ treatment that doesn’t deserve the label, it’s the ketogenic diet.

I’m not blaming individual physicians. The Institute of Medicine estimates that it takes 17 years for a proven therapeutic technique to become the standard of care. 17 years. That’s enough time for a child with infantile spasms to become a disabled young adult.

How can we increase the speed at which treatment paradigms in medicine shift? Because that’s what we’re talking about here. If the ketogenic diet were a new medication, it would have the support of Big Pharma. But it doesn’t make money for anyone, least of all the companies whose drugs these kids are often finally able to discontinue.

It’s just an alternative — no, a better — way of treating some children with epilepsy.


Lin Xu, Nicholas Rensing, Xiao-Feng Yang, Hai Xia Zhang, Liu Lin Thio, Steven M. Rothman, Aryan E. Weisenfeld, Michael Wong, Kelvin A. Yamada (2008). Leptin inhibits 4-aminopyridine– and pentylenetetrazole-induced seizures and AMPAR-mediated synaptic transmission in rodents Journal of Clinical Investigation, 118 (1), 272-280 DOI: 10.1172/JCI33009

E NEAL, H CHAFFE, R SCHWARTZ, M LAWSON, N EDWARDS, G FITZSIMMONS, A WHITNEY, J CROSS (2008). The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial The Lancet Neurology, 7 (6), 500-506 DOI: 10.1016/S1474-4422(08)70092-9

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HIV-Positive? Start Meditating Sat, 09 Aug 2008 17:17:11 +0000 Researchers at UCLA recently announced the results of a study of mindfulness medication among people with HIV. This isn’t the first team to look at the use of stress-reducing psychological and spiritual practices among people with HIV/AIDs. But it is the first team to look at the right outcome measure.

Studies of the impact of alternative and complementary therapies in immune-mediated diseases (chronic inflammatory processes, cancer, and HIV/AIDS) typically use mortality as the outcome of interest. You can make a good argument that this is fitting: avoiding death is, of course, the most ultimately meaningful outcome. However, using mortality as the outcome in studies of chronic, debilitating diseases is like saying that the best way to gauge the effectiveness of changing the oil in your car every 2,500 miles is whether or not it stops running in the next year or two. I don’t mean to trivialize the practice of mindfulness or being HIV-positive or having any other disease with this automotive analogy. I’m just trying to make a point about how loose the association often is between intervention and outcome in mortality studies — even though most try, with varying degrees of success, to control for some other factors that can influence mortality: age, comorbid conditions, stress levels, the use of antiretroviral therapy.

MeditationBut, until now, no study has focused solely on clinically meaningful intermediate outcomes.

The UCLA researchers measured the impact of  mindfulness-based stress reduction (MBSR) on CD4 T lymphocyte levels. These cells are the ones that the human immunodeficiency virus slowly eradicates.

The researchers took a small population of ethnically diverse and stressed HIV-positive people and, by random selection, separated them into two groups. The control group went to a one day seminar on MBSR. The other group augmented the one-day session with weekly two-hour training sessions and daily home practice.

People who participated in the eight-week program showed no decline in CD4 T cells. In contrast, T cell levels in members of the control group continued to decline over the course of the study. The researchers controlled for key factors, such as whether the participants were also taking antiretroviral medications.

Other than the small population size (48), the study design sidesteps the criticisms that are often leveled at CAM (complementary and alternative medicine) related research: no random selection, no control group. In fact, the use of one day of MBSR as the control criterion (as opposed to no MBSR at all) is brilliant, because the study suggests a dose-response effect. As the lead author, David Creswell, noted in a UCLA press release,

The more mindfulness meditation classes people attended, the higher the CD4 T cells at the study’s conclusion.


CRESWELL, J., MYERS, H., COLE, S., IRWIN, M. (2008). Mindfulness meditation training effects on CD4+ T lymphocytes in HIV-1 infected adults: A small randomized controlled trial. Brain, Behavior, and Immunity DOI: 10.1016/j.bbi.2008.07.004

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There Is No Sham In Acupuncture Tue, 29 Jul 2008 12:58:57 +0000 The randomized controlled trial (RCT) is the gold standard for evaluating whether or not a therapeutic modality works. In RCTs testing the effect of acupuncture to improve symptoms, researchers often use “sham acupuncture” as a control procedure, on the theory that sticking needles into points that are not on acupuncture meridians should have no effect.

The problem with this approach is that there is really no such thing as sham acupuncture.

In the mechanistic, Western view of the body and medicine, acupuncture is the sum of the parts, so it works like this:

problem + needle + point on meridian = problem gets better

AcupunctureYou can insert other things in place of “needle + point on meridian” and you’ll still have an accurate model for Western medicine.

problem + medication = problem gets better
problem + surgery = problem gets better

Each of these focuses on a specific functional or anatomic mechanism for ill health. High blood pressure? Take a beta blocker. Blocked coronary arteries? Replace them with femoral veins (better yet, internal mammary arteries).

In this view, placebos make perfect sense as a way of proving that interventions work:

problem + thing that looks like medication but isn’t = problem doesn’t get better

Here’s where the mechanistic view of the body and how medicine works fails to meet the holistic view. Acupuncture can’t be shoved into the mechanistic “if A, then B” box of randomized, controlled trials.

Solid evidence is emerging that the effects of acupuncture are mediated through the limbic-paralimbic-neocortical network. It plays a central role in the affective and cognitive dimensions of pain–and in regulating and integrating emotion, memory processing, autonomic, endocrine, immunological, and sensorimotor functions.

For instance, a recent study using functional MRI of the brain to trace the effects of acupuncture in the brain stimulated four points: Taichong (LV3), Xingjian (LV2), Neiting (ST44), and a sham point on the top of the left foot. The hemodynamic response was similar for all four points, as was the sensory experience as reported by the study subjects. Regardless of the point being needled, acupuncture produced extensive deactivation of the limbic-paralimbic-neocortical system.

In short, there is no such thing as sham acupuncture. Because the cognitive, affective, and physical intertwine in the limbic-paralimbic-neocortical network, there’s no way to have a needle stuck into you without experiencing at least some of the effects of acupuncture.

You might think that this would be good news for proponents of acupuncture. One way to interpret this information is that acupuncture is such a robust modality, it’s effective even when used outside traditional guidelines.

However this probably won’t come as a great surprise–from the Western perspective, interventions remain suspect if they can’t be isolated and controlled for. Even as acupuncture gains a toehold in Western medicine, it’s unlikely to ever be fully accepted as a treatment modality.


Fang, J., Jin, Z., Wang, Y., Li, K., Kong, J., Nixon, E.E., Zeng, Y., Ren, Y., Tong, H., Wang, Y., Wang, P., Hui, K.K. (2008). The salient characteristics of the central effects of acupuncture needling: Limbic-paralimbic-neocortical network modulation. Human Brain Mapping DOI: 10.1002/hbm.20583

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A Fatal Lack of Data Tue, 22 Jul 2008 14:59:32 +0000 I’ve been looking into violent deaths lately. And now I understand a few things.  Mostly, I understand what we don’t know about violent death in the United States. For instance, consider one of the most horrific kinds of violent death — mass shootings in public places like malls and offices and schools.

How often does this happen somewhere in the United States?

Nobody knows.

What kind of people wield the guns involved? How old are they? Do they have a criminal record or a history of mental illness?

Nobody knows.

How many murders involve assault weapons? How many are drug-related?

CrimeNobody knows.

How many teens are drunk or stoned when they commit suicide? How often does a child die from abuse somewhere in this country? How many women who die from domestic violence have a restraining order against their attacker?

Nobody knows.

I thought the answers to these questions would be easy to find. How wrong I was.

What I found was some information from a few states, but nothing systematic. Nothing that reports national-level data on violent death, which includes murder, suicide, domestic violence, and child abuse.

And I found a system that could provide this information. The National Violent Death Reporting System gathers data for every violent death from a variety of sources. By getting records from the police, medical examiners, crime labs, hospitals, and public health officials, the NVDRS can paint a picture of how and why people die the kind of deaths that spawn nightmares and media storms.

The NVDRS currently operates in 17 states. That’s all the funding there is. Housed at the Centers for Disease Control and Prevention, it depends on federal funding. It’s relatively inexpensive, too. Another $4 million for FY2009 would expand participation to more than half the states, so email your Congressional delegates.

Why should you bother? This isn’t just about having numbers. It’s about keeping people from becoming victims. Trying to prevent violent deaths without data about the how and why of it is like trying to treat cancer based on a biopsy report that’s missing most of the words. You might guess right, but the odds are against you.

And if you’re wrong, somebody dies.

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Are Placebos A Betrayal? Fri, 20 Jun 2008 13:41:12 +0000 Drugs and Clinical Trials CategoryIn recent years, there’s been a resurgence of interest in placebos. Not the kind that are used to minimize bias in clinical trials, but the kind that doctors knowingly give to patients.

In a recent survey of more than 200 doctors practicing in academic medical centers, 45% reported that they had given placebos to patients in the course of providing clinical care. Nearly all the physicians surveyed agreed with the statement that “placebos have therapeutic effects,” and the condition for which they believed placebos offered the most psychological and physiological benefit was pain.

PlaceboThey endorsed a variety of suggested definitions for placebo substances: half agreed with the statement that placebos are interventions “that are not expected to have an effect through a known physiologic mechanism.” The primary reasons physicians used placebos were to calm patients (18% of the time) and as supplemental treatment (also 18% of the time). One of the particularly noteworthy things about this study is that 92% of the doctors believed that the mechanism of action of the placebo was psychological. They weren’t giving the placebos to anxious patients simply to shut them up; they were invoking a mechanism of healing — the mind-body connection — that they believed in, even though they couldn’t specifically identify how it operated.

This is a sea change from “old school” thinking about how placebos fit into clinical practice. In a 1979 study, a majority of academic physicians reported believing that the use of placebos helped expose patients who were “faking” their symptoms. In contrast, 80% of the doctors in the more recent survey disagreed with the notion that placebos can be used to identify symptoms that have a psychogenic origin.

All good news so far, but there’s more. Only 4% of the physicians told the patient that the substance they were receiving was a placebo. Most used vague statements like, “This may help and won’t hurt” or “It’s medicine with no specific effect.” Just over 10% of the doctors in the survey believed that the use of placebos should be categorically prohibited on ethical grounds.

I try to imagine how my internist, who I respect immensely, would respond. Would he use a ruse to invoke the healing power of my mind? He’s seen me through a number of minor crises over the last 15 years, and I can’t imagine a circumstance under which this wouldn’t feel like a betrayal. Is it just me? Are there circumstances under which you’d be glad to have your doctor deceive you if it made you feel better?


Sherman, R., Hickner, J. (2008). Academic Physicians Use Placebos in Clinical Practice and Believe in the Mind–Body Connection. Journal of General Internal Medicine, 23(1), 7-10. DOI: 10.1007/s11606-007-0332-z

Goodwin, J.S., Goodwin, J.M., Vogel, A.V. (1979). Knowledge and use of placebos by house officers and nurses. Ann Intern Med, 91(1), 106-110.

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Mozart, MD – Music for the Mind and Body Mon, 16 Jun 2008 15:03:24 +0000 BioPsychoSocial Health CategoryMusic not only soothes the savage beast; it heals the critically ill.

A study in Critical Care Medicine evaluated the mechanisms of music-induced relaxation in critically ill patients. The researchers measured blood pressure and heart rate, brain electrical activity, serum levels of stress hormones and cytokines, requirements for sedative drugs, and level of sedation before and after an hour of listening to piano sonatas through headphones.

MozartResearchers found that patients who listened to the sonatas required less medication to achieve a comparable level of sedation, compared to those who didn’t.

One of the remarkable things about the study is that the researchers also found that serum levels of growth hormone went up after listening to music, while those of epinephrine and interleukin-6 went down. The levels of all three should decrease with lowered stress. The jury’s definitely still out on the mechanism by which this might occur, and bear in mind that this was an extremely small study: a total of just 10 patients in both intervention and control groups.

But not just any music will do. It has to be Mozart.

Another study compared the effect of listening to either Eine Kleine Nachtmusik or New Age music on relaxation states. Subjects were assigned to listen to either one for 28 minutes a day on three consecutive days. At the outset, all subjects scored similarly on the Smith Relaxation States Inventory.

On Day 2, Mozart listeners reported higher levels of a relaxation state called “At Ease/Peace” and lower levels of negative emotion. On Day 3, Mozart listeners reported substantially higher levels of the states of Mental Quiet, Awe and Wonder, Mystery, At Ease/Peace, and Rested/Refreshed than did those who listened to New Age music.

Researchers have demonstrated that listening to Mozart for ten minutes briefly improves performance on tests of spatial temporal reasoning and, most astoundingly, reduces epileptiform brain activity and clinical seizures. Mozart even works for mice. Those who were exposed to Mozart’s piano sonata K448 en utero and for 60 days after birth performed better at maze tests than mice who were exposed to silence, white noise, or music composed by Phillip Glass.

Computer analysis of the music of 58 composers revealed that Mozart was distinct in using long-term periodicity; that is, musical phrases lasting between 10 and 60 seconds with a definite beginning and end. Of all the music analyzed, only the Bach boys, J.S. and C.P.E., included similar periodicity.

Take two sonatas and call me in the morning.


Conrad, C., Niess, H., Jauch, K.W., Bruns, C.J., Hartl, W., Welker, L. (2007). Overture for growth hormone: requiem for interleukin-6?. Critical Care Medicine, 35(12), 2709-2713.

Hughes, J.R., Fino, J.J. (2000). The Mozart effect: distinctive aspects of the music–a clue to brain coding?. Clinical EEG, 31(2), 94-103.

Smith, J.C., Joyce, C.A. (2004). Mozart versus new age music: relaxation states, stress, and ABC relaxation theory. Journal of Music Therapy, 41(3), 215-224.

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Mind-Body: We Want Evidence, Don’t We? Tue, 10 Jun 2008 14:01:23 +0000 Alternative Medicine CategoryI spend my days poring over medical research reports and databases, looking for high-quality evidence to build compelling arguments. And, when it comes to mind-body treatment modalities, I can’t find it. I’m not sure I want what it will take to get it, either.

I find small studies that lack control groups or testing for statistical significance. I find review articles that end like this: “More trials are needed” or “Future research… must be more rigorous in the design and execution of studies and in the analysis and reporting of results.”

MeditationThe lack of evidence doesn’t keep people from meditating, doing yoga, or practicing mindfulness. But it does relegate mind-body modalities to a second-class citizen status among treatment options. Medicine is evidence-based, so we should expect mind-body interventions to follow the rules of the game: large randomized controlled trials (RCTs) with rigorous statistical analysis.

The National Center for Complementary and Alternative Medicine, one of 27 divisions at the National Institutes of Health, is the US federal government’s lead agency for scientific research on complementary and alternative medicine (CAM). With a FY2008 appropriation of $121.5 million, it’s the largest single source for funding CAM-related research.

Browsing through the list of projects funded in 2007, I look forward to reading the reports of studies like these:

  • Neuroimaging acupuncture effects on human brain activity
  • Tai Chi mind-body therapy for congestive heart failure
  • Reiki and physiological consequences of acute stress
  • Mindfulness-based stress reduction for high blood pressure

My fear is that many of the results will be equivocal. By their very nature, CAM modalities consist of interventions that don’t fit the tightly-controlled mold of RCTs. How can you gauge the “effective dose” of reiki, for instance? Never mind whether it’s consistent across practitioners or patients or over time.

Even with controlled, consistent interventions, several studies are often required to create a clear picture of efficacy. The number of studies that NCCAM can fund with its minuscule annual appropriation (compare it to the National Cancer Institute’s proposed 2009 budget of $5 billion) isn’t enough to allow inconclusive or non-significant results to be balanced by other findings.

Trying to fit CAM into the RCT mold might actually jeopardize its transition to first-class citizen status.

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