With former San Francisco 49ers' star Dwight Clark the latest pro football player diagnosed with ALS, also known as Lou Gehrig's disease, now comes the question: Is there a connection between head trauma suffered by pro football players and the degenerative disease? For an answer, I consulted Dr. Dale J. Lange, neurologist-in-chief at Hospital for Special Surgery in New York City and current president of the New York State Neurological Society, for insight into a crippling disorder that, in the past year, claimed the lives of former NFL players Mickey Marvin and Kevin Turner and that seems to affect a greater percentage of football players than it does the general population. What follows is our discussion:
Q:What defines ALS, and how is it diagnosed?
DR. LANGE: ALS is a pretty easy diagnosis to make, but the point is that it's a clinical diagnosis. There is only one situation where we can unequivocally make a diagnosis with ALS, and that is when it's inherited. About 10 percent of the patients with ALS have an inherited disease, (and) we know the mutation. There are several different mutations, but we know that in about 60 to 70 percent of the people with inherited disease we can identify the mutation. And once we identify the mutation in the appropriate person with weakness we know the diagnosis ... and it really can't be anything else. In the vast majority of patients that have ALS, and I don't know anything about Mr. Clark's family history, but if I extrapolate his condition to the other football players or sports players who have had this disease, most of them are non-familial. We make the diagnosis through a couple of fairly unique -- but not totally unique -- clinical features, and that is you have progressive weakness and wasting of muscle in multiple levels of the nervous system. So that would be arms, legs, breathing, speaking and swallowing. Our level of confidence increases when we have weakness and wasting and muscle twitching in multiple segments of the nervous system because ALS is a complete motor system disease, which means it affects the brain's contribution to the motor system, as well as the spinal cord's contribution. So when the spinal cord produces weakness and wasting and twitching, the brain's contribution makes the limb become hyperactive. And the combination of weakness, wasting and twitching, plus over-reactive reflex actions, kind of makes the clinical diagnosis of ALS. Once you have those, it's incumbent upon the clinician to make sure that there are no other potential causes that can mimic this illness. And there are very few. Long story short: It is a clinical diagnosis. There are no diagnostic markers. Those of us in the research world are trying desperately to find a marker for this disease to help us be sure of the diagnosis, but we don't have it yet.
Q: I notice that you're involved in clinical and science research that investigates new ways to treat patients with weakness and impaired mobility. What advances in the treatment of ALS have been made the last 10 years?
DR. LANGE: I think we divide it into two segments. One is the advance in treating people with the familial disease, and that's one area that we are very excited about because we have a cause. And I think if we can hit that one, we can extrapolate to the sporadic disease. So if we can silence the genes that we know or somehow make the products of those mutations less toxic, we think we're on our way to mitigating the progression or even stopping the illness, which we can do in animals. Those treatments are actually in clinical trials now, and we're excited about that.
To say that repeated head trauma is a case of ALS overstates our knowledge. But to say that it is associated with ALS is true.
Q: So there have been successes?
DR. LANGE: It's too early The trials are probably within a year of getting started. So I can't say that. But the basis of the trials are the strongest that we've ever had. The scientific basis and the rationale are extraordinarily strong, and we're very excited about the possibility of slowing patients with inherited diseases -- either slowing or stopping that syndrome. We're making extraordinary advances in treating genetic diseases. Over the last two years we've made remarkable changes in being able to delete mutations. In familial ALS, we're using genetic tools to silence abnormal genes, and we think it really should make a difference in stopping the disease so it's not really long term. Depending upon the degree, we can silence the gene, and we should have an appropriate decrease in progression. In (treating)sporadic disease we've had a couple of really interesting findings, and probably the most interesting is the use of stem cells. So stem-cell therapy in ALS in sporadic disease is giving us some very interesting and exciting signals that may well also cause a slowing of the disorder.
Q: I've read that there are approximately 6,000 cases of ALS diagnosed in the United States every year and saw a 2012 study that concluded pro football players are four times as likely to die from ALS or Alzheimer's as the general public. True?
DR. LANGE: The only data that we really have is the article that you quote, and there is some pathophysiology to support that. I think to say that repeated head trauma is a cause of ALS overstates our knowledge. But to say that it is associated with ALS is true. But that's been going back for many years. There are articles in the 80s and 90s, if I'm remember correctly, that previous head trauma was always statistically significantly more in patients with ALS. And, so, if you look at previous history, head trauma would stand out as being, not 90 percent, but more than the control group. Once chronic traumatic encephalopathy (CTE) was identified by the people in Pittsburgh and followed up by the people in Boston, we were able to try to connect the two. And I think it's making a story that makes sense -- although we can't prove it yet -- that the findings that are induced by repeated trauma causes problems with the brain that may predispose people to particular forms of dementia, as well as ALS. The exact mechanism is unclear, but there certainly are interesting hypothetical scenarios that would suggest that the interruption of the neurons in the brain causes an impairment of metabolic flow in the neurons, and that induces a situation that may lead the nerve to accumulate toxic proteins. And one of the things that we know is that both in ALS and dementia there are accumulations of what we call aggregates that are found in the neurons of people with CTE, as well as ALS and regular Alzheimer's. And those aggregates are now thought to be instrumental in the propagation of the disease, which is really what we're talking about -- basically, that the neurons die. So that's how, at the present time, we're connecting the two events. And I think we all believe there's a connection. It's just not a cause and effect. There are loads of people who have repeated head trauma who don't develop dementia and who don't develop ALS, but certainly it is one of the risk factors for you to develop one of those two degenerative diseases.
Q: So while there's no direct correlation between concussions and ALS, you're saying there's an increased risk of incurring the disease if you've suffered repeated head trauma. Correct?
DR. LANGE: That's our understanding now. There's just no question that people who have repeated concussions (are more susceptible) ... however you define concussions -- (maybe more like) repeated head trauma, but I'm not so sure concussions are the sine qua non of this. Then you have to have a threshold. (So) is it: You can't get hit more than 20 times? (What about) the increased prevalence in soccer players? Is it because of the head trauma that they do with the ball? I think we're at a point where we know repeated concussive or head trauma ... and the quantity is not known ... will predispose the brain to chronic traumatic encephalopathy, and those findings can evolve into either dementia, ALS or both.
Q: Athletes generally are in superior physical condition to the general public. Does that superior condition help them in managing the symptoms of ALS once they're affected?
DR. LANGE: The interesting question is: Does their superior physical condition put them at any increased risk of developing ALS? And I just posed that. There's no strong data for and against it. There's been a big debate in the neurological community as to whether or not aggressive exercise ... or exercise in any sort of way ... is a risk factor for ALS. One of the features that we all have seen is that ALS is relatively uncommon in very under active, obese (patients). It's not unheard of. But the better condition you're in, it seems to the clinician that (that individual) will make up the majority of your practice rather than the person who is not in condition and is moderately obese and doesn't take care of himself.