Concussion—A Public Health Crisis

SAN FRANCISCO—Concussion is a public health crisis, given the huge population at risk and the limitations of current diagnostic and treatment methods, according to an overview on imaging concussion presented at the Seventh Annual Winter Conference of the Headache Cooperative of the Pacific.

Although many experts consider concussion to be a functional disturbance rather than a structural injury, it is associated with structural abnormalities. Similarly, although guidelines state that evidence of concussion is rarely found on conventional neuroimaging, some neurologists question this assertion.

“Concussion is a structural injury, and in most cases it is not normal on standard imaging modalities,” said David W. Dodick, MD, Professor of Neurology at the Mayo Clinic in Phoenix. But many concussions are silent, and most go unreported, often because an athlete wants to continue to play in a game. In addition, neurologists have no biomarker for concussion and no definitive treatment.

Players Endure Multiple Hits
Although a single concussion can have long-term sequelae, repeated hits to the head are of particular concern. A recent study found that varsity football and hockey players sustain an average of 1,000 hits each season at a mean acceleration of 20 G—a force comparable to that of a car driving at 35 mph and hitting a brick wall, said Dr. Dodick.

In another recent study, researchers used functional MRI to test cognition in football players ages 15 to 19 before and after the playing season. Although none of the athletes tested had had a symptomatic concussion, their ability to complete the assigned task and their overall cognitive function were markedly lower postseason. The extent of impairment correlated with the number of hits to the head that they had sustained.

The near death of a high school football player from second impact syndrome led to laws limiting postconcussion return to play in all 50 states. Although children may be sidelined for 30 days, however, cognitive symptoms can take six weeks or more to resolve—and 44% to 50% of athletes have three or more symptoms at one year.

Researchers Find Evidence of Degenerative Disease
After repeated head injuries, athletes are at high risk for chronic traumatic encephalopathy (CTE), the progressive neurodegenerative disease that helped raise public awareness of the danger associated with sports-related trauma. Researchers at Boston University have examined the brains of more than 100 deceased athletes and found evidence of tauopathy in 70 of them, reported Dr. Dodick. Unlike the neurofibrillary tangles found in Alzheimer’s disease, those characteristic of CTE cluster in the subcortical regions of the brain.

Researchers at the University of California, Los Angeles, successfully used PET scans with tau ligand to detect in vivo evidence of CTE. They scanned the brains of five retired football players and found tau deposits associated with trauma in each.

“Metabolic brain imaging with tau ligand is perhaps one of the greatest advances in the field,” said Dr. Dodick. Although CTE usually develops within five to 10 years of an athlete’s retirement, early indicators of the disease were found in the brain of a 17-year-old football player who committed suicide.

When Is Postconcussion Imaging Indicated?
The Institute of Medicine’s sports-related concussion guideline states that traditional CT and MRI are of little diagnostic value. The American Academy of Neurology calls for CT only when a more serious traumatic brain injury (TBI) is suspected. The Zurich consensus statement concludes that CT and MRI contribute little to the evaluation of concussion.

“If I stopped here, you would go back and say, ‘There is no need to image the brain in routine concussion,’” Dr. Dodick said. He went on to review both traditional and newer imaging modalities and the Mayo Clinic’s unvalidated concussion protocol, which recommends imaging for every patient.

CT Is Overused, but MRI Can Be Revealing
CT is the mainstay of imaging TBI in an emergency setting, but it has little value in the evaluation of concussion in outpatient settings, said Dr. Dodick. Even in emergency departments, overuse is increasingly common and costly and unnecessarily exposes patients to high doses of radiation.

Although the role of MRI in concussion is controversial, “we image everybody who comes to us for concussion evaluation,” said Dr. Dodick. MRI can detect contusions, edema, traumatic axonal injury (TAI), and subacute or remote hemorrhages that CT often misses. In a study of 135 patients with mild TBI, 27% of those with normal CT scans had abnormal MRIs.

Susceptibility-Weighted Imaging
The Mayo Clinic’s protocol includes susceptibility weighted imaging (SWI), with brain imaging sequences including sagittal T1 and axial 3D T1, axial T2, 3D fluid attenuated inversion recovery, single voxel magnetic resonance spectroscopy (MRS), and axial diffusion tensor imaging (DTI). SWI “is probably the most important thing we do,” said Dr. Dodick.

He recalled the case of a 19-year-old hockey player whom he was asked to clear for return to play. Gradient echo imaging was normal, as were the athlete’s neurologic exam and impact test, but SWI revealed multiple areas of TAI.

Magnetic Resonance Spectroscopy
Sometimes referred to as a virtual biopsy, MRS detects changes in metabolites in the brain. Most notably, the technique identifies changes in N-acetylaspartate (NAA), a marker of neuronal and axonal health that declines in TBI.

In a study of professional soccer players with a baseline NAA:creatine ratio greater than 2, participants’ postconcussion ratio was less than 2. Although the athletes reported complete symptom resolution on day 3, brain imaging did not return to normal for one month or longer. Because of the lag time between symptom resolution and metabolic recovery, Dr. Dodick said, “I’m cautious, with children and youth in particular, about sending them back to play.”

Diffusion Tensor Imaging
DTI, another element of the Mayo Clinic’s concussion protocol, is based on the diffusivity of water, which is variably restricted in different tissues. In CSF, for example, diffusion of water is isotropic. In white matter, diffusion is highly anisotropic, and a reduction of fractional anisotropy (FA) correlates with the loss or destruction of white matter.

Multiple DTI studies have been conducted in the past 30 years. Despite various limitations, the findings provide striking evidence of small and subtle brain abnormalities in most athletes, said Dr. Dodick. A study comparing patients with mild TBI vs patients with moderate-to-severe TBI, for example, found a graded alteration in white matter integrity. Patients with mild TBI also had abnormalities.

Notably, evidence of abnormalities has been found even in the absence of symptomatic concussion. “You can alter brain structure and function without clinical symptomatology,” said Dr. Dodick.

Patients may ask whether these brain changes are reversible. Dr. Dodick described a patient who underwent DTI immediately after concussion and again 16 months later. At the time of the second imaging, the abnormal reduction of FA showed a loss of integrity. “That [injury] probably does not repair itself,” he said. At least in some cases, the changes can be persistent.

Current Imaging Can Guide Clinical Practice
“There is great potential for advanced brain imaging of concussion,” said Dr. Dodick, “but you can detect and characterize brain abnormalities that will guide your clinical decision making” here and now. Even if testing is limited to SWI, he added, it will identify many abnormalities that otherwise would be missed.

If in vivo testing for CTE is proven to be effective, “we’ll be able to premortem early detect those at risk for neurodegenerative disease,” said Dr. Dodick. “The holy grail, of course, is that this would be used in future research to evaluate interventions and new treatments.”

—Helen Lippman

SAN FRANCISCO—Concussion is a public health crisis, given the huge population at risk and the limitations of current diagnostic and treatment methods, according to an overview on imaging concussion presented at the Seventh Annual Winter Conference of the Headache Cooperative of the Pacific.

Although many experts consider concussion to be a functional disturbance rather than a structural injury, it is associated with structural abnormalities. Similarly, although guidelines state that evidence of concussion is rarely found on conventional neuroimaging, some neurologists question this assertion.

“Concussion is a structural injury, and in most cases it is not normal on standard imaging modalities,” said David W. Dodick, MD, Professor of Neurology at the Mayo Clinic in Phoenix. But many concussions are silent, and most go unreported, often because an athlete wants to continue to play in a game. In addition, neurologists have no biomarker for concussion and no definitive treatment.

Players Endure Multiple Hits
Although a single concussion can have long-term sequelae, repeated hits to the head are of particular concern. A recent study found that varsity football and hockey players sustain an average of 1,000 hits each season at a mean acceleration of 20 G—a force comparable to that of a car driving at 35 mph and hitting a brick wall, said Dr. Dodick.

In another recent study, researchers used functional MRI to test cognition in football players ages 15 to 19 before and after the playing season. Although none of the athletes tested had had a symptomatic concussion, their ability to complete the assigned task and their overall cognitive function were markedly lower postseason. The extent of impairment correlated with the number of hits to the head that they had sustained.

The near death of a high school football player from second impact syndrome led to laws limiting postconcussion return to play in all 50 states. Although children may be sidelined for 30 days, however, cognitive symptoms can take six weeks or more to resolve—and 44% to 50% of athletes have three or more symptoms at one year.

Researchers Find Evidence of Degenerative Disease
After repeated head injuries, athletes are at high risk for chronic traumatic encephalopathy (CTE), the progressive neurodegenerative disease that helped raise public awareness of the danger associated with sports-related trauma. Researchers at Boston University have examined the brains of more than 100 deceased athletes and found evidence of tauopathy in 70 of them, reported Dr. Dodick. Unlike the neurofibrillary tangles found in Alzheimer’s disease, those characteristic of CTE cluster in the subcortical regions of the brain.

Researchers at the University of California, Los Angeles, successfully used PET scans with tau ligand to detect in vivo evidence of CTE. They scanned the brains of five retired football players and found tau deposits associated with trauma in each.

“Metabolic brain imaging with tau ligand is perhaps one of the greatest advances in the field,” said Dr. Dodick. Although CTE usually develops within five to 10 years of an athlete’s retirement, early indicators of the disease were found in the brain of a 17-year-old football player who committed suicide.

When Is Postconcussion Imaging Indicated?
The Institute of Medicine’s sports-related concussion guideline states that traditional CT and MRI are of little diagnostic value. The American Academy of Neurology calls for CT only when a more serious traumatic brain injury (TBI) is suspected. The Zurich consensus statement concludes that CT and MRI contribute little to the evaluation of concussion.

“If I stopped here, you would go back and say, ‘There is no need to image the brain in routine concussion,’” Dr. Dodick said. He went on to review both traditional and newer imaging modalities and the Mayo Clinic’s unvalidated concussion protocol, which recommends imaging for every patient.

CT Is Overused, but MRI Can Be Revealing
CT is the mainstay of imaging TBI in an emergency setting, but it has little value in the evaluation of concussion in outpatient settings, said Dr. Dodick. Even in emergency departments, overuse is increasingly common and costly and unnecessarily exposes patients to high doses of radiation.

Although the role of MRI in concussion is controversial, “we image everybody who comes to us for concussion evaluation,” said Dr. Dodick. MRI can detect contusions, edema, traumatic axonal injury (TAI), and subacute or remote hemorrhages that CT often misses. In a study of 135 patients with mild TBI, 27% of those with normal CT scans had abnormal MRIs.

Susceptibility-Weighted Imaging
The Mayo Clinic’s protocol includes susceptibility weighted imaging (SWI), with brain imaging sequences including sagittal T1 and axial 3D T1, axial T2, 3D fluid attenuated inversion recovery, single voxel magnetic resonance spectroscopy (MRS), and axial diffusion tensor imaging (DTI). SWI “is probably the most important thing we do,” said Dr. Dodick.

He recalled the case of a 19-year-old hockey player whom he was asked to clear for return to play. Gradient echo imaging was normal, as were the athlete’s neurologic exam and impact test, but SWI revealed multiple areas of TAI.

Magnetic Resonance Spectroscopy
Sometimes referred to as a virtual biopsy, MRS detects changes in metabolites in the brain. Most notably, the technique identifies changes in N-acetylaspartate (NAA), a marker of neuronal and axonal health that declines in TBI.

In a study of professional soccer players with a baseline NAA:creatine ratio greater than 2, participants’ postconcussion ratio was less than 2. Although the athletes reported complete symptom resolution on day 3, brain imaging did not return to normal for one month or longer. Because of the lag time between symptom resolution and metabolic recovery, Dr. Dodick said, “I’m cautious, with children and youth in particular, about sending them back to play.”

Diffusion Tensor Imaging
DTI, another element of the Mayo Clinic’s concussion protocol, is based on the diffusivity of water, which is variably restricted in different tissues. In CSF, for example, diffusion of water is isotropic. In white matter, diffusion is highly anisotropic, and a reduction of fractional anisotropy (FA) correlates with the loss or destruction of white matter.

Multiple DTI studies have been conducted in the past 30 years. Despite various limitations, the findings provide striking evidence of small and subtle brain abnormalities in most athletes, said Dr. Dodick. A study comparing patients with mild TBI vs patients with moderate-to-severe TBI, for example, found a graded alteration in white matter integrity. Patients with mild TBI also had abnormalities.

Notably, evidence of abnormalities has been found even in the absence of symptomatic concussion. “You can alter brain structure and function without clinical symptomatology,” said Dr. Dodick.

Patients may ask whether these brain changes are reversible. Dr. Dodick described a patient who underwent DTI immediately after concussion and again 16 months later. At the time of the second imaging, the abnormal reduction of FA showed a loss of integrity. “That [injury] probably does not repair itself,” he said. At least in some cases, the changes can be persistent.

Current Imaging Can Guide Clinical Practice
“There is great potential for advanced brain imaging of concussion,” said Dr. Dodick, “but you can detect and characterize brain abnormalities that will guide your clinical decision making” here and now. Even if testing is limited to SWI, he added, it will identify many abnormalities that otherwise would be missed.

If in vivo testing for CTE is proven to be effective, “we’ll be able to premortem early detect those at risk for neurodegenerative disease,” said Dr. Dodick. “The holy grail, of course, is that this would be used in future research to evaluate interventions and new treatments.”

—Helen Lippman

SAN FRANCISCO—Concussion is a public health crisis, given the huge population at risk and the limitations of current diagnostic and treatment methods, according to an overview on imaging concussion presented at the Seventh Annual Winter Conference of the Headache Cooperative of the Pacific.

Although many experts consider concussion to be a functional disturbance rather than a structural injury, it is associated with structural abnormalities. Similarly, although guidelines state that evidence of concussion is rarely found on conventional neuroimaging, some neurologists question this assertion.

“Concussion is a structural injury, and in most cases it is not normal on standard imaging modalities,” said David W. Dodick, MD, Professor of Neurology at the Mayo Clinic in Phoenix. But many concussions are silent, and most go unreported, often because an athlete wants to continue to play in a game. In addition, neurologists have no biomarker for concussion and no definitive treatment.

Players Endure Multiple Hits
Although a single concussion can have long-term sequelae, repeated hits to the head are of particular concern. A recent study found that varsity football and hockey players sustain an average of 1,000 hits each season at a mean acceleration of 20 G—a force comparable to that of a car driving at 35 mph and hitting a brick wall, said Dr. Dodick.

In another recent study, researchers used functional MRI to test cognition in football players ages 15 to 19 before and after the playing season. Although none of the athletes tested had had a symptomatic concussion, their ability to complete the assigned task and their overall cognitive function were markedly lower postseason. The extent of impairment correlated with the number of hits to the head that they had sustained.

The near death of a high school football player from second impact syndrome led to laws limiting postconcussion return to play in all 50 states. Although children may be sidelined for 30 days, however, cognitive symptoms can take six weeks or more to resolve—and 44% to 50% of athletes have three or more symptoms at one year.

Researchers Find Evidence of Degenerative Disease
After repeated head injuries, athletes are at high risk for chronic traumatic encephalopathy (CTE), the progressive neurodegenerative disease that helped raise public awareness of the danger associated with sports-related trauma. Researchers at Boston University have examined the brains of more than 100 deceased athletes and found evidence of tauopathy in 70 of them, reported Dr. Dodick. Unlike the neurofibrillary tangles found in Alzheimer’s disease, those characteristic of CTE cluster in the subcortical regions of the brain.

Researchers at the University of California, Los Angeles, successfully used PET scans with tau ligand to detect in vivo evidence of CTE. They scanned the brains of five retired football players and found tau deposits associated with trauma in each.

“Metabolic brain imaging with tau ligand is perhaps one of the greatest advances in the field,” said Dr. Dodick. Although CTE usually develops within five to 10 years of an athlete’s retirement, early indicators of the disease were found in the brain of a 17-year-old football player who committed suicide.

When Is Postconcussion Imaging Indicated?
The Institute of Medicine’s sports-related concussion guideline states that traditional CT and MRI are of little diagnostic value. The American Academy of Neurology calls for CT only when a more serious traumatic brain injury (TBI) is suspected. The Zurich consensus statement concludes that CT and MRI contribute little to the evaluation of concussion.

“If I stopped here, you would go back and say, ‘There is no need to image the brain in routine concussion,’” Dr. Dodick said. He went on to review both traditional and newer imaging modalities and the Mayo Clinic’s unvalidated concussion protocol, which recommends imaging for every patient.

CT Is Overused, but MRI Can Be Revealing
CT is the mainstay of imaging TBI in an emergency setting, but it has little value in the evaluation of concussion in outpatient settings, said Dr. Dodick. Even in emergency departments, overuse is increasingly common and costly and unnecessarily exposes patients to high doses of radiation.

Although the role of MRI in concussion is controversial, “we image everybody who comes to us for concussion evaluation,” said Dr. Dodick. MRI can detect contusions, edema, traumatic axonal injury (TAI), and subacute or remote hemorrhages that CT often misses. In a study of 135 patients with mild TBI, 27% of those with normal CT scans had abnormal MRIs.

Susceptibility-Weighted Imaging
The Mayo Clinic’s protocol includes susceptibility weighted imaging (SWI), with brain imaging sequences including sagittal T1 and axial 3D T1, axial T2, 3D fluid attenuated inversion recovery, single voxel magnetic resonance spectroscopy (MRS), and axial diffusion tensor imaging (DTI). SWI “is probably the most important thing we do,” said Dr. Dodick.

He recalled the case of a 19-year-old hockey player whom he was asked to clear for return to play. Gradient echo imaging was normal, as were the athlete’s neurologic exam and impact test, but SWI revealed multiple areas of TAI.

Magnetic Resonance Spectroscopy
Sometimes referred to as a virtual biopsy, MRS detects changes in metabolites in the brain. Most notably, the technique identifies changes in N-acetylaspartate (NAA), a marker of neuronal and axonal health that declines in TBI.

In a study of professional soccer players with a baseline NAA:creatine ratio greater than 2, participants’ postconcussion ratio was less than 2. Although the athletes reported complete symptom resolution on day 3, brain imaging did not return to normal for one month or longer. Because of the lag time between symptom resolution and metabolic recovery, Dr. Dodick said, “I’m cautious, with children and youth in particular, about sending them back to play.”

Diffusion Tensor Imaging
DTI, another element of the Mayo Clinic’s concussion protocol, is based on the diffusivity of water, which is variably restricted in different tissues. In CSF, for example, diffusion of water is isotropic. In white matter, diffusion is highly anisotropic, and a reduction of fractional anisotropy (FA) correlates with the loss or destruction of white matter.

Multiple DTI studies have been conducted in the past 30 years. Despite various limitations, the findings provide striking evidence of small and subtle brain abnormalities in most athletes, said Dr. Dodick. A study comparing patients with mild TBI vs patients with moderate-to-severe TBI, for example, found a graded alteration in white matter integrity. Patients with mild TBI also had abnormalities.

Notably, evidence of abnormalities has been found even in the absence of symptomatic concussion. “You can alter brain structure and function without clinical symptomatology,” said Dr. Dodick.

Patients may ask whether these brain changes are reversible. Dr. Dodick described a patient who underwent DTI immediately after concussion and again 16 months later. At the time of the second imaging, the abnormal reduction of FA showed a loss of integrity. “That [injury] probably does not repair itself,” he said. At least in some cases, the changes can be persistent.

Current Imaging Can Guide Clinical Practice
“There is great potential for advanced brain imaging of concussion,” said Dr. Dodick, “but you can detect and characterize brain abnormalities that will guide your clinical decision making” here and now. Even if testing is limited to SWI, he added, it will identify many abnormalities that otherwise would be missed.

If in vivo testing for CTE is proven to be effective, “we’ll be able to premortem early detect those at risk for neurodegenerative disease,” said Dr. Dodick. “The holy grail, of course, is that this would be used in future research to evaluate interventions and new treatments.”

—Helen Lippman