Friday, February 10, 2012

When the Zebra is a Horse

Is this a zebra, a horse, or a Photoshop disaster?*

Here's a trivia question for the doctor-folks who follow my blog:  What's the most common cause of encephalitis of uncertain etiology in children and young adults?  Hint: It's not herpes, rabies or even West Nile.

It's anti-NMDA receptor encephalitis.

If you already know what I'm talking about, I'm impressed.  I had never heard of this entity until today, when our chair forwarded everyone in the medicine department a report from the California Encephalitis Project (CEP).  In fact, anti-NMDAR wasn't even discovered until 2007.

Encephalitis is inflammation of the brain, resulting in fever, confusion, seizures and sometimes permanent neurologic damage and death.  It's usually caused by viruses and sometimes bacteria, when it accompanies meningitis.  Anti-NMDAR is not an infection, however.  NMDA is a ubiquitous neurotransmitter, and in this disease, the body produces antibodies that attack the NMDA receptor, leading to gross neurological dysfunction. 

Anti-NMDAR can be a devastating illness.  It presents with hallucinations, language problems and vital sign instability, among other signs and symptoms.  In the CEP report, 40% of patients required life support for respiratory failure.  Fortunately, there is effective treatment for anti-NMDAR.  The majority respond to a potent cocktail of immune suppression -- the exact opposite of how you would normally treat infectious encephalitis.

And here's the surprising part of the report:  Out of 761 cases of encephalitis reported over the 3 to 4 year period, 47 were tested for NMDAR because of clinical suspicion.  Thirty-two, or 68%, tested positive.  In fact, even though only a fraction of cases were tested for anti-NMDAR, it was the most common cause of encephalitis in this case series.  Two-thirds of cases were in children.

Now encephalitis is still a very rare illness, with an incidence rate of 1 out of 200,000 in the U.S., so even if anti-NMDAR is a common cause of encephalitis, it's still an extremely uncommon disease.  (Please do not charge into your pediatrician's office demanding to have little Johnny tested because he has a fever or is moodier than usual.)  The CEP only collected cases of encephalitis of unknown etiology, so many of the diagnosed viral cases were excluded from this analysis, artificially inflating the relative frequency of anti-NMDAR.  On the other hand, because so few doctors are aware of this disease, we are probably undertesting and missing cases.

In medicine, we have a saying:  When you hear hoofbeats, think of horses, not zebras.  In other words, don't go on an expensive hunt for a rare disease unless you have a compelling reason to do so.  When it comes to childhood encephalitis, though, anti-NMDAR may turn out to be the proverbial horse.

*It's a zorse (zebra-horse hybrid).

Wednesday, February 8, 2012

It's Not Easy Eating Green

A reader sent me a recent article about methods used throughout history to get children to take their medicines.  While the piece focused on sweet talk and sweeteners, the biogeek in me was drawn to a comment about a new compound, GIV3616, that blocks the bitter taste receptors on the tongue.  A scientist from Givaudan Flavors, developer of this chemical, noted that for veggie-phobic children, "We’d like to be able to make their diets more enjoyable by masking the off-putting flavors of bitterness. Blocking these flavors we call off-notes could help consumers eat healthier and more varied diets."  I was dying to get a hold of this bitter blocker to sprinkle on my picky daughter's kale, but that would probably alienate those of you who eschew genetically modified, irradiated, non-organic, non-sustainable, non-locally produced Frankenfoods.  Besides, when I did a Google Scholar search on this compound, nothing has been published -- not even animal safety studies.  (I'm sure it's proprietary.)

It turns out there's a cheaper, low tech solution to increasing vegetable consumption in kids.  This week in JAMA, a psychologist, an economist, a marketing professor and two nutritionists walk into a bar published a study in which they placed photographs of vegetables in elementary school lunch tray compartments.  They measured vegetable consumption on a day when the trays had the photographs and compared it to a day when they didn't have the photographs.  These valiant researchers (or more likely, their undergraduate assistant in charge of "data acquisition") went so far as to scrape off and weigh uneaten vegetables left on the trays, tables and floors.

Does your kid's lunch tray look like this....

...or this?

So what did they find?  On the positive side, the percentage of children scooping green beans and carrots into those compartments went up from 6-12% to 15-37%, and overall consumption increased modestly.  On the downside, a lot of the kids left their veggies uneaten (in fact, more carrots were wasted in the photograph group), and even with the overall increase, consumption still did not meet government recommendations.  The study was also performed over a mere two days.  Kids will figure out in no time that no one's going to punish them if they scoop pudding into a green bean compartment.

As for me, I'll keep waiting for that magic bullet.  To the marketing geniuses at Givaudan:  hurry up, rechristen your license-plate chemical "Flavia," and release it to the general public. And  one more favor, if you please: Publish a study showing your bitter blocker won't make my daughter grow a third eyeball.*

*What's more likely is that she would grow more bitter taste receptors in response to chronic blockade.  (That's the mechanism by which people become tolerant to narcotics or alcohol).  If she were to suddenly stop using the chemical, she would be more sensitive to bitterness than ever before.