Lou Gehrig Probably Died of Lou Gehrig's Disease

OR: Why news embargoes are bad for science.

In an example of mainstream reporting that is aptly described as a "jumbled ball of confusion", the New York Times claimed that baseball player Lou Gehrig (who died in 1941 and whose remains were cremated) might not have had Lou Gehrig's disease:

A peer-reviewed paper to be published Wednesday in a leading journal of neuropathology, however, suggests that the demise of athletes like Gehrig and soldiers given a diagnosis of amyotrophic lateral sclerosis, commonly known as Lou Gehrig’s disease, might have been catalyzed by injuries only now becoming understood: concussions and other brain trauma.

Although the paper does not discuss Gehrig specifically, its authors in interviews acknowledged the clear implication: Lou Gehrig might not have had Lou Gehrig’s disease.

Amyotrophic lateral sclerosis (ALS) is a horrible progressive disease that causes the degeneration of motor neurons that control the muscles. Patients with ALS gradually lose the ability to walk, eat, and breathe on their own. This can happen in a relatively short amount of time (Mitchell & Borasio, 2007):

The clinical features of amyotrophic lateral sclerosis are indicative of the loss of neurons at all levels of the motor system—from the cortex to the anterior horn of the spinal cord. Physical signs of this disorder thus encompass both upper motor neuron and lower motor neuron findings. Objective sensory findings are incompatible with a diagnosis of amyotrophic lateral sclerosis unless they can be accounted for by neurological comorbidity. The course of the disorder is inexorably progressive, with 50% of patients dying within 3 years of onset.

Gehrig died two years after his diagnosis.

What is the evidence that Gehrig might have died from brain trauma and not ALS? According to the New York Times, the forthcoming paper in the Journal of Neuropathology & Experimental Neurology presents postmortem findings from three patients:

...markings in the spinal cords of two players and one boxer who also received a diagnosis of A.L.S. indicated that those men did not have A.L.S. at all. They had a different fatal disease, doctors said, caused by concussionlike trauma, that erodes the central nervous system in similar ways.

From that limited evidence we see extrapolation to a dead sports hero who suffered a number of concussions during his playing career. Gary Schwitzer's HealthNewsReview Blog provides an excellent summary of what was wrong with this coverage, and I suggest you read beyond the excerpt below:

NYT's unfounded leap: Lou Gehrig might not have had Lou Gehrig's disease

This was one time when the headline was OK, but the story that followed had our heads spinning. "Study Says Brain Trauma Can Mimic Lou Gehrig's Disease" is a story that was troubling on a number of fronts. It reported on a study which at the time had not yet been published suggesting that some "athletes and soldiers given a diagnosis of amyotrophic lateral sclerosis...might have been catalyzed by injuries only now becoming understood: concussions and other brain trauma."

To be clear - and please don't anyone miss or miscontrue this point - this is an important and fascinating area of research.

But the story did not exhibit the best of health/medical/science journalism.

Why is it bad that the study has not yet been published? Because experts in the field are not able to read the article and report on what it actually showed. Because the news coverage gets worse, much worse. As in this outright lie printed by The Guardian:

Lou Gehrig killed by baseball not Lou Gehrig's disease, study finds

Player who gave his name to a type of motor neurone disease more probably died due to brain trauma

On the other hand, here's the more modest press release from the journal publisher:

Head Trauma in Pro Athletes Linked to Motor Neuron Disease

Released: 8/17/2010 11:50 AM EDT
Source: Wolters Kluwer Health: Lippincott Williams & Wilkins

Football Players and Boxers with ALS-Like Condition Show Specific Patterns of Protein Deposits in Brain

Newswise — Professional athletes with repetitive head trauma—and possibly others with a history of head injuries many years previously—may be prone the development of a motor neuron disease similar to amyotrophic lateral sclerosis (ALS or "Lou Gehrig's disease"), reports a study in the September Journal of Neuropathology & Experimental Neurology, official journal of the American Association of Neuropathologists, Inc...

"This is the first pathological evidence that repetitive head trauma experienced in collision sports might be associated with the development of a motor neuron disease," according to the study by Dr. Ann C. McKee of Boston University School of Medicine and colleagues.

Specific Brain Abnormalities Linked to Motor Neuron Disease in Athletes with Head Trauma
The researchers used sophisticated neuropathology techniques to study specific proteins, called tau and TDP-43, in brains obtained at autopsy from twelve former athletes. Eleven of the athletes had been professional football players or boxers; one was a hockey player.

The study actually included neuropathological findings from 12 brains {all 12 had chronic traumatic encephalopathy, but only 3 had ALS}. The embargoed paper is likely to be very good research on an important topic. In addition, there is good evidence that mild traumatic brain injury IS a risk factor for neurodegeneration, as shown by the same group of investigators (Gavett et al., 2010).

The overblown and downright erroneous claims propagated by the press are unfortunate. Will more people read, click, and buy [and fund research] if the name of a historical baseball figure is invoked? I guess so. Some of the blame must be shared by the senior author of the paper, Dr. Ann McKee, who offered up the following quotes in an interview:

“Here he is, the face of his disease, and he may have had a different disease as a result of his athletic experience.”

. . .

“If we can create this in laboratory mice, which are easily genetically altered and breed quickly, we can learn about the pathogenesis of this disorder, and then provide treatment,” Dr. McKee said.

Three postmortem cases --> genetically altered mice --> treatment.

Uh, aren't we jumping the gun just a bit? Even though the chronic traumatic encephalopathy (CTE) variant of ALS-like disease may have a different etiology, drug development will not be easy. According to the ALS Association:

Present treatment of ALS includes one drug, riluzole (Rilutek©) and is aimed at symptomatic relief, prevention of complications and maintenance of maximum optimal function and optimal quality of life. Most of this, in the later stages, requires substantial physical caregiving. Click here for more information on Rilutek.

For information on drug development and clinical trials, click here.

Riluzole slows the progression of ALS but is not a cure. Neurodegenerative diseases exact a terrible toll on patients and their families. Sufficient funding for the development of effective treatments is of critical importance. But do we have to warp the news coverage to obtain such funding? Such is the sorry state of scientific research today.

References

Gavett BE, Stern RA, Cantu RC, Nowinski CJ, McKee AC. (2010). Mild traumatic brain injury: a risk factor for neurodegeneration. Alzheimers Res Ther. 2:18.

Mitchell JD, Borasio GD. (2007). Amyotrophic lateral sclerosis. Lancet 369:2031-41. Review.