The stunning announcement Sunday that former 49ers star Dwight Clark had been diagnosed with ALS immediately raised the question:

Did football cause this?

And it was Clark himself, in a letter to his fans, who posed it.

“I have ALS, also known as Lou Gehrig’s disease,” Clark wrote. “Those words are still very hard for me to say. I’ve been asked if playing football caused this. I don’t know for sure. But I certainly suspect it did.”

Clark continued: “I encourage the NFLPA and the NFL to continue working together in their efforts to make the game of football safer, especially as it relates to head trauma.”

So what are the connections, proven by research or simply implied by circumstantial suggestion, between the game of football and a degenerative neurological disease that afflicts 6,000 more people each year and claims the lives of half of them within three to five years of diagnosis?

The affliction, which is a progressive compromise of muscles due to nerve degeneration, manifests itself at first with weakness in the arms or legs but eventually can lead to the muscles simply shutting down. Attacking the respiratory system, ALS often turns fatal when a patient succumbs to pneumonia.

The ALS-sports link is made all the more pronounced because of the famed athletes who have perished at its touch. Usually striking people between the ages of 40 and 70, at time when sports stars are looking back on storied careers from the perch of middle age, ALS has claimed a long list of professionals: Hall of Fame pitcher Jim “Catfish” Hunter,  boxing champion Ezzard Charles, NBA Hall of Fame basketball player George Yardley, pro football player Glenn Montgomery, British soccer player Jimmy Johnstone, and others.

And, of course, there is no sports figure more connected to ALS than Lou Gehrig, the New York Yankees legendary first-baseman who in 1939 abruptly retired from baseball after being diagnosed with ALS.

For years, studies have linked ALS, along with conditions caused by brain-cell damage like Alzheimer’s disease, to the world of professional football players. In 2012, researchers from the National Institute for Occupational Safety and Health in Cincinnati wrote in the journal Neurology that pro football players are much more likely to die from these diseases. Their research gathered data on 3,439 ex-professional football players, average age 57 years, who had played during at least five seasons from 1959 to 1988 for the NFL. Poring over death certificates, the team discovered that gridiron veterans had triple the risk of death caused by diseases that destroy or damage brain cells compared to other people. And they had four times greater risk of dying from ALS or Alzheimer’s disease.

There is conflicting research about possible links between ALS and CTE, or chronic traumatic encephalopathy, which affects professional athletes who have had repeated head injuries and has been the focus of the largest share of recent concerns about football’s health legacies. Writing on the ALS Association website, Dr. Edward Kasarskis with the ALS Center at the University of Kentucky Neuroscience Center in Lexington, Kentucky, suggested a cautious approach to linking the two.

Kasarskis said a study published in the Journal of Neuropathology and Experimental Neurology  in 2010 reported that some “professional athletes (football, boxing) who have had repeated head injuries and developed what’s called chronic traumatic encephalopathy (CTE) may develop ALS. This study, based on the examination of the brain and spinal cord at autopsy, indicated that some pathological features of CTE in the brain can extend to the spinal cord. However, there were problems with the way the findings were reported by the media.”

As he wrote, “the majority of people with head trauma do not develop ALS. Head trauma is not rare; there are about 300,000 cases of head trauma every year. But there are about 5,600 cases of ALS annually.

“CTE is not a motor neuron disease, and there is no clear-cut cause-and-effect relationship between CTE and ALS,” wrote Kasarskis. “Some large, population based studies have provided evidence that head trauma might be one of many contributing factors involved in sporadic ALS, but much more work needs to be done in this area.”

Among the most famous cases in the annals of football and ALS was the story of Paul Kevin Turner, a former player for the New England Patriots and the Philadelphia Eagles who died last year at age 46 from ALS. Yet even in his death, Turner’s diagnosis stirred controversy, as news outlets reported – erroneously – that CTE, and not ALS, had killed him. Turner was a key figure in the shared history of the NFL and brain-damage disorders as he served as a lead plaintiff in a major lawsuit filed by former players against the NFL regarding the health risks of concussions in American football.

Following Turner’s death last March, Boston University Brain CTE Center announced that Turner had had  a severe case of CTE which led to his death. The Boston University School of Medicine posted on its Facebook Page, “The VA-BU-CLF Brain Bank issued the following statement: To clarify conflicting media reports, #KevinTurner died of #ALS. ALS is a clinical diagnosis defined by the loss of movement through the degeneration of motor neuron cells. There are many known causes of ALS, specifically genetic and environmental causes, but most ALS cases are of idiopathic, or unknown, origin. By studying his brain, researchers at the VA, Boston University School of Medicine and Concussion Legacy Foundation discovered that the cause of Kevin Turner’s ALS was motor neuron cell death triggered by CTE, which is a pathological diagnosis. His clinical diagnosis remains ALS.”

Sports fans and writers have increasingly called on the NFL to take ALS and related disorders more seriously. Mark Purdy, a columnist for this news organization, wrote that the league has made some fledgling efforts in recent years to try and reduce the frequency of concussions among players, including the so-called ”88 Plan” which helps pay medical bills for those players diagnosed with dementia,  ALS, or Parkinson’s disease.

“But the league has never focused specifically on the potential links between football and dementia,” Purdy wrote. “Or football and ALS. Or football and various other neurological terrors. The league has also never specifically raised barrels of money to research ALS cures or treatments. Neither has the NFLPA, the players’ union.”

Purdy wasn’t hopeful that things would change anytime soon. “My suspicion?  Lawyers are advising the league not to get too close to the ALS flame, for fear of creating a liability disaster.  And perhaps the NFLPA fears that it it acknowledges the possible links now, former members might sue the union for not better informing them of the risks in past seasons.”