More and more research has raised concern over the dangers of concussions – one of the most common forms of head trauma – as many sufferers go on to experience persistent neurological symptoms throughout their lives.

Now, scientists have discovered a clue as to why mild traumatic brain injuries (MTBI) can have such long-lasting health consequences.

In a study published in the journal Radiology, researchers found that white matter damage in the brains of people who had experienced concussions closely resembled the type of white matter damage found in patients with Alzheimer’s disease.  These findings suggest that concussions set off a chain of neurological events that can cause long-term damage to the brain.

“It’s not the hitting your head that’s the problem.  It’s everything else that happens after that,” said lead study author Dr. Saeed Fakhran, assistant professor of radiology in the Division of Neuroradiology at the University of Pittsburgh School of Medicine.

Concussions affect more than 1.7 million people in the United States annually – and around 15 percent of those people suffer lasting neurological symptoms.

Typically, when people experience concussions, CT and MRI scans of their brains look normal and doctors have remained largely in the dark regarding the best ways to treat these types of injuries, according to Fakhran.

Fakhran and his colleagues decided to take a closer look at the impact concussions were having on the brain. Researchers gathered data from 64 MTBI patients, with a mean age of 17, and 15 control patients. Thirty-nine percent of the MTBI patients had suffered a prior concussion and two-thirds of the patients had suffered a concussion as a result of a sports-related injury.

“We used something called diffusion tensor imaging, which is a subset of MRI looking at just the white matter,” Fakhran said. “It looks at areas where your white matter is injured.”

Due to the white matter injuries seen on the patients’ scans, researchers were able to hypothesize that when a person hits his or her head, it sets off a chain of events in the brain that can potentially lead to long-lasting neurological damage.

“Most people will tell you if you hit your head, you get a concussion, and the damage comes from the act of hitting your head,” Fakhran said. “(But) maybe the hitting your head is lighting the fuse and the damage  comes from a neurodegenerative cascade (afterwards).”

If doctors can figure out how to stop the chain of damage that occurs in the brain after a concussion, Fakhran said they may be able to mitigate some of the side effects associated with the injury.

“If you look through medical record of kids with concussions, some of them have horrible consequences…Their school work falls off a cliff…It’s really scary to think about,” Fakhran said.

One of the most disabling side effects of concussions is sleep-wake disturbances, which disrupt sleep and can seriously decrease quality of life in patients, leading to memory problems and even social dysfunction.

“Imagine not sleeping all night and having to go to work and sit at work all day.  You’re not able to concentrate, your grades at school will fall. If you can’t sleep, you can’t function,” Fakhran said.

A subset of the patients in Fakhran’s study suffered from sleep-wake disturbances – which researchers were able to link to abnormalities in the hippocampus area of the brain. Fakhran pointed out that one of the earliest signs of Alzheimer’s disease is sleep-wake disturbances.

Though more research is needed, the scientists hope that by pinpointing the areas of the brain in which various concussion symptoms originate, they will be able to find a way to stop those symptoms before they progress and cause long-term neurological problems.

“Hitting your head is lighting the fuse. If you lit the fuse and I blow it out, you just have a bruise, no damage done. But if you don’t, then it gets down to the bottom and explodes. To me the explosion is Alzheimer’s,” Fakhran said.

1. For athletes, what factors increase or decrease concussion risk?

2a. For athletes suspected of having sustained concussion, what diagnostic tools are useful in identifying those with concussion?

2b. For athletes suspected of having sustained concussion, what diagnostic tools are useful in identifying those at increased risk for severe or prolonged early impairments, neurologic catastrophe, or chronic neurobehavioral impairment?

3. For athletes with concussion, what clinical factors are useful in identifying those at increased risk for severe or prolonged early postconcussion impairments, neurologic catastrophe, recurrent concussions, or chronic neurobehavioral impairment?

4. For athletes with concussion, what interventions enhance recovery, reduce the risk for recurrent concussion, or diminish long-term sequelae?

The new AAN recommendations — divided into preparticipation counseling; assessment, diagnosis, and management of suspected concussion; and management of diagnosed concussion — were nicely summarized at the press event by lead authors Christopher C. Giza, MD, and Jeffrey S. Kutcher, MD. However, some areas of the guideline are open to interpretation, particularly when it comes to deciding when it is acceptable to allow an athlete with a suspected concussion to return to play. The following summary serves as a guide to the new report, highlighting the major recommendations and providing additional clarification based on comments from Drs. Giza and Kutcher.

Preparticipation Counseling

• School-based professionals education
• Inform athletes/families of concussion risk factors
• Disseminate risk information to schools and athletic authorities

School-based professionals who may encounter SRCs should be educated by an experienced licensed healthcare provider (LHCP), defined by the guideline committee as “an individual who has acquired knowledge and skills relevant to evaluation and management of sports concussions and is practicing within the scope of his or her training experience.” LHCPs — including both sideline- and clinic-based clinicians — should be designated by their organization as being qualified to accurately convey concussion risks to athletes and their families and should take it upon themselves to deliver this information. LHCPs can also facilitate providing concussion risk information to school systems and athletic organizations or authorities.

Suspected Concussion

• Instruct inexperienced LHCPs in the use of standardized assessment tool
• Use standardized assessment tools
• Ensure communication between sideline LHCPs and clinical LHCPs
• Obtain baseline scores
• Remove the athlete from play
• No return to play without clearance by an LHCP
• Don’t perform imaging to diagnose SRC
• Do perform imaging to rule out serious TBI

Inexperienced LHCPs should be instructed by LHCPs who have concussion experience in the appropriate use of “standardized validated sideline assessment tools.” Sideline LHCPs should initially apply assessment tools and relay findings to appropriate clinical LHCPs. Obtaining baseline assessment scores to have on hand is recommended to facilitate more accurate postinjury scores.

The next recommendation was a source of some confusion at the AAN 2013 press conference. The guidelines state that “any athlete suspected of having sustained a concussion” should be immediately removed from play to minimize the risk for further injury. There has long been an idea that a “second hit” in close proximity to a previous head injury may result in cumulative injury beyond the sum of the 2 single hits (in other words, 2 + 2 = 5 in terms of brain injury), but this hypothesis has not been proven in athletes.

There is also accumulating evidence that repeated mild head injury, particularly concussion, may result in chronic traumatic encephalopathy (CTE). However, research on CTE is still in its early phase, and the role of repeated concussions in the development of CTE requires better definition.

Because this is an evidence-based guideline, the above concerns regarding repetitive head injury are not the basis for the recommendation for removing the athlete from play. That recommendation is based on robust epidemiologic evidence that people who experience a single concussion are more likely to experience another one compared with people who never had one (6 class I studies[2-7] and 1 class II study[8]). Furthermore, that risk is particularly increased in the 10 days after the first concussion (2 class I studies[9,10]). Because of this strong evidence that a single concussion predisposes to a second one, the guideline advises that players exit the game and not return until symptoms resolve.

The reason for this increased risk for a second injury is unknown. The most likely hypothesis is that impaired cognition or physical reflexes due to the first concussion increase the player’s susceptibility to injury.

The AAN guideline insists that players who experience symptoms suggestive of concussion, such as blurry or double vision, confusion, dizziness, headache, nausea, memory loss, or other cognitive or behavioral problems, must have full resolution of their symptoms (off medication) and approval for return to play by an LHCP. This approach would seem to allow players who had transient symptoms after a mild head injury to return to play if they felt better on the sidelines and had no discernible neurologic deficit. When asked about this, Dr. Kutcher explained that the player could not return to play that day if a concussion had been diagnosed, even if symptoms had cleared. This recommendation is echoed by the American Medical Society for Sports Medicine position statement, which clearly prohibits same-day return to play for an athlete diagnosed with a concussion.[11]

A potential loophole for return to play is for the player who sustains a concussion, but denies symptoms and has no objective findings on examination. This player might be hiding symptoms, but in the absence of any neurologic findings would be able to return to play because no diagnosis of concussion was made.

A second situation not addressed by the guidelines, and pointed out by some reporters attending the press conference, is the player who has a head injury but whose concussive symptoms don’t appear until after the game. This player would have been allowed to resume play, potentially putting him or her at risk for a second head injury. Because the diagnosis of concussion requires symptoms or signs, in both of these scenarios the players could return to play, even after witnessed collisions involving their heads. Although concussion symptoms may take hours to days to manifest, most concussive symptoms appear within minutes to hours, according to Dr. Kutcher.

Less open to interpretation are the AAN’s recommendations for neuroimaging in athletes with a suspected concussion. They state that CT is not appropriate in diagnosing SRC, because SRC is a clinical diagnosis that does not depend on radiologic findings. However, CT can be obtained to rule out more severe TBI, including intracranial hemorrhage in cases of suspected concussion and loss of consciousness, posttraumatic amnesia, focal neurologic deficits, persistently altered mental status, potential skull fracture, or signs of clinical deterioration.

Diagnosed Concussion

• Return to play is prohibited until concussion has resolved
• Return to play is prohibited until the player is asymptomatic off medication
• High-school age or younger athletes: Take a more conservative approach to return to play
• Preteen athletes: Ensure appropriate assessment tools
• Consider neurocognitive testing
• Consider individual management plans
• Consider cognitive restructuring
• There is no indication for “absolute rest” after a concussion

In athletes with a diagnosed concussion, the AAN recommendations prohibit return to play or to practice until an LHCP is convinced the concussion has resolved and the player is asymptomatic off medication. This caution is intended to diminish the risk for recurrent or additional injury; athletes with residual reflex or cognitive impairment are potentially at higher risk for another concussion. A more conservative return-to-play approach is recommended in athletes of high school age or younger, because younger athletes seem to take longer to recover than older athletes. Ensuring that assessment tools are age-appropriate is encouraged.

In determining whether a concussion has resolved, LHCPs can use supplemental neurocognitive testing, including comparisons with age-matched normal profiles or a patient’s baseline profile. Furthermore, LHCPs can consider using individualized management and return-to-play plans with careful monitoring. Cognitive restructuring — a form of psychological counseling that includes education, reassurance, and reattribution of symptoms — is also recommended, because data suggest that it may lessen the risk for developing postconcussion syndrome.
Multiple Concussions/Persistent Impairment: Retirement From Play Decisions
The Basics

• Professional athletes: Refer for neurologic and neuropsychological assessment
• Amateur athletes: Perform formal neurologic/cognitive assessment, and offer risk factor counseling
• Professional contact-sport athletes with chronic impairment: Recommend retirement

When determining whether retirement from play should be considered in professional athletes with a history of multiple concussions and persistent neurobehavioral impairments, LHCPs can consider referring for neurologic and neuropsychological testing. In amateur athletes with multiple concussions and continued impairment, formal neurologic and cognitive assessment tools are also recommended. This population of athletes should be counseled on the risk for developing chronic neurobehavioral or cognitive impairment. For professional athletes with chronic impairment who play a contact sport, retirement is recommended.
Conclusions

Concussion remains a clinical syndrome that depends on a clinical history of head injury or sudden force, typical symptoms, and findings on physical examination. The AAN guideline represents an important first step to highlight the importance of recognition and management of concussion in amateur and professional athletes. These guidelines provide a basis for a consistent approach to amateur and professional athletes with mild head injuries, which should facilitate daily management at the sidelines and ringside.

Although concussions in professional athletes receive most of the press, concussions in youth sports are actually more numerous. Coaches, parents, physicians, and schools will benefit from these practical guidelines in addressing the frequent occurrence of sports-related mild head injuries.

It seems that the AAN has chosen the term “licensed healthcare provider” in order to include all medical practitioners who participate in sports medicine, acknowledging that those likely to assess athletes may not necessarily be physicians. These may include certified athletic trainers, neurologists, neuropsychologists, neurosurgeons, orthopedists, physician assistants, pediatricians, sports medicine doctors, and others. The guideline also asserts that these LHCPs must be “trained in diagnosing and managing concussion,” which emphasizes the need for proper training regardless of one’s specialty or degree. Ultimately, the management of each athlete with a concussion must be individualized.

Many questions remain regarding the pathophysiology of concussion and the best approach to facilitate brain healing. For example, what exactly is the nature of the injury at the tissue and cellular level that accounts for a patient’s symptoms? What is it about a first concussion that predisposes to a second? How much “healing” takes place after a concussion vs “rerouting” of signaling to compensate for the injury? Does rapid return to play after symptom resolution engage the brain and promote healing or is prolonged rest a better approach? Can helmet technology be improved to prevent concussions? Now that concussion is on everyone’s radar, perhaps research efforts will receive additional impetus, and the answers to these and other important questions will be forthcoming sooner rather than later.
References

1. Giza CC, Kutcher JS, Ashwal S, et al. Summary of evidence-based guideline update: evaluation and management of concussion in sports: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013 March 18. [Epub ahead of print]
2. Guskiewicz IM, Weaver NL, Padua DA, Garrett WE Jr. Epidemiology of concussion in collegiate and high school football players. Am J Sports Med. 2000;28:643-650. Abstract
3. Hollis SJ, Stevenson MR, McIntosh AS, Shores EA, Collins MW, Taylor CB. Incidence, risk, and protective factors of mild traumatic brain injury in a cohort of Australian nonprofessional male rugby players. Am J Sports Med. 2009;37:2328-2333. Abstract
4. Guskiewicz KM, McCrea M, Marshall SW, et al. Cumulative effects associated with recurrent concussion in collegiate football players: the NCAA Concussion Study. JAMA. 2003;19:2549-2555.
5. Delaney TS, Lacroix VJ, Leclerc S, Johnston KM. Concussions among university football and soccer players. Clin J Sport Med. 2002;12:331-338. Abstract
6. Emery CA, Kang J, Shrier I, et al. Risk of injury associated with body checking among youth ice hockey players. JAMA. 2010;303:2265-2272. Abstract
7. Dick R, Hootman JM, Agel J, Vela L, Marshall SW, Messina R. Descriptive epidemiology of collegiate women’s field hockey injuries: National Collegiate Athletic Association Injury Surveillance System, 1988-1989 through 2002-2003. J Athl Train. 2007;42:211-220. Abstract
8. Dick R, Lincoln AE, Agel J, Carter EA, Marshall SW, Hinton RY. Descriptive epidemiology of collegiate women’s lacrosse injuries: National Collegiate Athletic Association Injury Surveillance System, 1988-1989 through 2003-2004. J Athl Train. 2007;42:262-269. Abstract
9. Guskiewicz KM, McCrea M, Marshall SW, et al. Cumulative effects associated with recurrent concussion in collegiate football players: the NCAA Concussion Study. JAMA. 2003;19:2549-2555.
10. Dick R, Lincoln AE, Agel J, Case JG, Marshall SW. Descriptive epidemiology of collegiate men’s lacrosse injuries: National Collegiate Athletic Association Injury Surveillance System, 1988-1989 through 2003-2004. J Athl Train. 2007;42:255-261. Abstract
11. Harmon KG, Drezner JA, Gammons M, et al. American Medical Society for Sports Medicine position statement: concussion in sport. Br J Sports Med. 2013;47:15-26.

Twenty-seven percent of mTBI patients with a normal CT scan showed evidence of abnormalities on brain MRI.

MRI may be better than CT scans at predicting whether patients with mild traumatic brain injuries (mTBI) are likely to have persistent neurologic problems, according to the results of a clinical trial published in the December 2012 Annals of Neurology.

Approximately 15% of patients with mTBI have measurable neurologic deficits at one year after injury, but clinicians have no definitive method of predicting patient outcomes.

To address this clinical need, Esther Yuh, MD, PhD, Assistant Professor in Residence at the University of California, San Francisco, School of Medicine, and her colleagues examined the potential of MRI to predict patient outcome three months after mTBI. The researchers prospectively followed 135 patients who were evaluated for acute head injury in the emergency departments of three level I trauma centers—San Francisco General Hospital and Trauma Center, the University of Pittsburgh Medical Center, and the University Medical Center Brackenridge in Austin, Texas. These centers were part of the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study (TRACK-TBI).

Patient Characteristics

Patients came from highly diverse socioeconomic backgrounds, had few exclusion factors, and ranged from age 15 to 86, with a mean age of 40. All patients underwent CT scans when they were admitted, and early brain MRI was performed approximately a week later.

The investigators used univariate and multivariate logistic regression to determine demographic, clinical, socioeconomic, CT, and MRI features that predicted outcomes at three months following the brain injury. Outcomes were assessed with the eight-point Extended Glasgow Outcome scale, a well-validated summary assessment suitable for clinical trials.

Multivariate models of the three-month outcome scale were analyzed based on three sets of predictive variables. The first set examined only clinical, demographic, and socioeconomic variables, the second set incorporated head CT features, and the third set used all the preceding variables, as well as brain MRI features.

Evidence of subarachnoid hemorrhage on CT was associated with a multivariate odds ratio of 3.5 for poorer three-month outcome, after accounting for demographic, clinical, and socioeconomic factors, said the researchers.

Normal CT Is Not Enough

However, 27% of patients who were admitted with normal head CT had an abnormal early brain MRI. After adjusting for head CT findings and demographic, clinical, and socioeconomic factors, the investigators found that one or more brain contusions and four or more foci of hemorrhagic axonal injury on MRI were each independently associated with poorer three-month outcome. Multivariate odds ratios were 4.5 and 3.2, respectively.

This work raises questions of how we’re currently managing patients via CT scan,” said senior author Geoff Manley, MD, PhD, Chief of Neurosurgery at San Francisco General Hospital. “Having a normal CT scan doesn’t, in fact, say you’re normal,” he added.

A Step Forward

Each year, at least 1.7 million Americans seek medical attention for acute head injuries, and 75% of those injuries are mTBIs, most with mild symptoms such as temporary loss of consciousness, vomiting, or amnesia.

The majority of patients with mTBI recover fully, but approximately one in six eventually develop persistent and sometimes permanent disability from the injury. In the past, some socioeconomic factors have helped to predict disability, but Dr. Yuh’s study shows that an imaging feature can help to predict the rate or extent of a patient’s recovery.

According to Dr. Manley, this study represents an important step toward developing a more quantitative, precise method of evaluating, monitoring, and treating patients with mTBI. At present, performing routine brain MRI on mTBI patients may not be cost-effective, but smaller and less-costly MRI scanners that examine only the patient’s head are in development. Furthermore, continuing advances in the MRI field may eventually reduce expenses to a manageable level.

The study’s strengths are its greater specification of types of lesions that may predict outcome, control for other predictors, multicenter patient sample, and use of TBI Common Data Elements to categorize the imaging results, the investigators said.

They believe the findings will benefit clinicians and researchers conducting clinical trials. “Progress beyond mere definition of mTBI toward evidence-based diagnosis is essential for clinical trials that evaluate treatments and, ultimately, more effective triage to follow-up care,” stated the authors.(Lauren LeBano)

Concern has grown over concussion brain injuries in professional athletes as well as in teens and children. Youngsters — whose brains are still developing — are competing at ever-earlier ages in concussion-prone contact sports. The concern spotlights the need for more awareness of concussion dangers and how to prevent them.

A concussion occurs when there’s a blow to the head or a sudden jolt that shakes the head and causes the brain’s gelatin-like cortex to rapidly collide into or bounce off the inside of your skull or to rotate within it. When it occurs, the brain’s function is altered. Loss of consciousness may or may not happen, which is one of the reasons some concussions go unrecognized.

No matter the cause, when a firsttime concussion brain injury is identified and the brain is given adequate rest and time to heal properly, most recover completely. However, changes that occur in the brain due to concussion make it potentially vulnerable to repeat injury and possibly even permanent damage. For someone who’s had multiple concussions, recovery becomes less certain with each concussion.

Inside matter

According to the Centers for Disease Control and Prevention, concussions make up the majority of traumatic brain injuries each year. Among adults 65 and older, falls are the number one cause of traumatic brain injury. For all
age groups, motor vehicle accidents are the second-leading cause. Part of the concussion conundrum is that the brain has no pain receptors. So, during a concussion — when the brain is slung through its cushion of cerebrospinal
fluid and crashes full force into the cranium — that impact registers indirectly. Initially, or within several minutes, you may experience confusion and memory loss. This may or may not be preceded by loss of consciousness.

Although you may appear to be fine immediately after a concussion, it’s a different story inside the brain. The instant after a concussion the brain is in crisis. Many brain cells (neurons) can become activated all at once. This can
cause a sudden release of brain chemicals (neurotransmitters). Within minutes to hours after a concussion, the brain’s power drain produces signs and symptoms that may include headache, dizziness, imbalance, nausea or vomiting, slurred speech, fatigue and being unaware of your surroundings.

While some symptoms are more immediate, others may show up in the hours and days that follow, including:

• Difficulty concentrating or remembering things
• Sensitivity to light and noise
• Persistent headache
• Unexplained irritability or other personality changes
• Sleep disturbances
• Depression and problems adjusting psychologically
• Altered senses of taste and smell

As long as symptoms are present, it’s critically important to avoid a second concussion. During this time, the brain is vulnerable to a rare but fatal brain-swelling complication.

Long-term changes from a brain concussion are more uncertain. Although symptoms due to concussion may no longer be apparent, structural damage to the brain may be slower to recover. Recent studies using specialized
magnetic resonance imaging (MRI) scans show changes in certain brain structures even at six months.

Medical care matters

A head injury should be evaluated by a medical professional. That person may be your care primary doctor or any other member of your primary health care team capable of giving you advice and assuring follow-up. Young athletes or children should be removed from play for any suspected concussion.

Typically, a neurological exam is done for a head injury. This may include evaluation of your memory and ability to concentrate, vision and hearing, pupils, strength and sensation, balance, coordination, and reflexes.
Although brain imaging isn’t always done, depending on your symptoms, a computerized tomography (CT) scan or MRI may be done to assess the brain right after injury. However, the findings are usually normal. Imaging is also likely if you’re 65 years of age or older or are taking medicines that affect blood clotting.

Depending on the findings, you may need to be hospitalized overnight for observation. Monitoring is important in the hours after a concussion because brain injury may lead to more-serious problems, including bleeding in or around the brain.

If your doctor says home observation is reasonable, you’ll need to have someone check on you every few hours for at least 24 hours to be sure that your symptoms don’t get any worse. Emergency
care is needed if your symptoms get worse or you experience any of the following:

• Repeated vomiting
• Severe headache
• Loss of consciousness
• Difficulty with mental function or physical coordination

Time for recovery

Because the brain is fragile after a concussion, the focus during recovery is rest — both physical and mental. It takes time for the brain to restore itself. And how much time varies. Several factors can influence how quickly you
recover, including your age, severity of the concussion and whether you have other health conditions. Recovering from a concussion is no time to ignore your symptoms and “tough it out” — doing so can make
symptoms worse. Instead:
■ Take time to rest — Get plenty of sleep at night and rest during the day.
■ Moderate how much and how intensely you think — Special imaging scans show that thinking causes the brain to use energy, which is fine when the brain isn’t in the process of healing. But after a concussion, energy use from
thinking takes away from the brain’s efforts to heal and recover. Concentration slows recovery and can even make symptoms worse. That’s why it’s important to avoid activities that require a lot of concentration.
■ Avoid physically demanding activities — Put your workout aside for now. Let someone else mow the lawn or clean the house. Save the energy you have each day for activities that are most important to you.

If your doctor says you can ease into some regular activities, see how you do. If your symptoms return or you get new symptoms, more rest is needed.

When concussion recovery is managed properly, most people recover completely within a week or two and have no further symptoms. However, for those whose recovery from concussion takes longer, persistent headache
can be a common challenge.

Read full article at http://healthletter.mayoclinic.com/year/year.cfm/i/2012

Methods.— A cross-sectional, questionnaire-based study was conducted with a cohort of 978 U.S. soldiers who screened positive for a deployment-related concussion upon returning from Iraq or Afghanistan. All soldiers underwent a clinical evaluation at the Madigan Traumatic Brain Injury Program that included a history, physical examination, 13-item self-administered headache questionnaire, and a battery of cognitive and psychological assessments. Soldiers with CDH, defined as headaches occurring on 15 or more days per month for the previous 3 months, were compared to soldiers with episodic headaches occurring less than 15 days per month.

Results.— One hundred ninety-six of 978 soldiers (20%) with a history of deployment-related concussion met criteria for CDH and 761 (78%) had episodic headache. Soldiers with CDH had a median of 27 headache days per month, and 46/196 (23%) reported headaches occurring every day. One hundred seven out of 196 (55%) soldiers with CDH had onset of headaches within 1 week of head trauma and thereby met the time criterion for posttraumatic headache (PTHA) compared to 253/761 (33%) soldiers with episodic headache. Ninety-seven out of 196 (49%) soldiers with CDH used abortive medications to treat headache on 15 or more days per month for the previous 3 months. One hundred thirty out of 196 (66%) soldiers with CDH had headaches meeting criteria for migraine compared to 49% of soldiers with episodic headache. The number of concussions, blast exposures, and concussions with loss of consciousness was not significantly different between soldiers with and without CDH. Cognitive performance was also similar for soldiers with and without CDH. Soldiers with CDH had significantly higher average scores on the posttraumatic stress disorder (PTSD) checklist compared to soldiers with episodic headaches. Forty-one percent of soldiers with CDH screened positive for PTSD compared to only 18% of soldiers with episodic headache.

Conclusions.— The prevalence of CDH in returning U.S. soldiers after a deployment-related concussion is 20%, or 4− to 5-fold higher than that seen in the general U.S. population. CDH following a concussion usually resembles chronic migraine and is associated with onset of headaches within the first week after concussion. The mechanism and number of concussions are not specifically associated with CDH as compared to episodic headache. In contrast, PTSD symptoms are strongly associated with CDH, suggesting that traumatic stress may be an important mediator of headache chronification. These findings justify future studies examining strategies to prevent and treat CDH in military service members following a concussive injury.

Introduction

Over 160,000 U.S. military service members have been diagnosed with traumatic brain injury since 2000.^[1] Concussions occur in 15–23% of U.S. service members deployed in support of Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF).^[2–4] Headache is one of the most common symptoms after a concussion and may persist for months to years after injury. The prevalence of headaches in returning U.S. military service members who had a concussion while deployed to Iraq or Afghanistan ranges from 22% to 97%.^[2,3,5]

Chronic daily headache (CDH), defined as 15 or more headache days per month, is one of the most disabling headache syndromes with a prevalence of 4–5% in the general population.^[6,7] A number of primary headache disorders may manifest as CDH. Chronic migraine is one of the most common and most disabling forms of CDH among primary headache disorders. Secondary headache disorders can also manifest as CDH. Head trauma has been suggested as an important risk factor in the development of chronic daily headache in civilians. It has been estimated that 15% of cases of CDH in the general population are attributable to head or neck trauma.^[8]

Little is known about CDH in military populations. Given the association between head trauma and CDH in civilians, we hypothesized that CDH would be highly prevalent among service members who had a concussion while serving in Iraq or Afghanistan. We previously reported the prevalence, characteristics, and impact of headaches in a large cohort of returning U.S. soldiers who had a concussion while deployed to Iraq or Afghanistan.^[5] The aim of the current study was to determine the prevalence and characteristics of, and factors associated with, CDH in this same cohort of U.S. soldiers who had a deployment-related concussion.

Methods

This study was approved by the Madigan Army Medical Center Institutional Review Board. A cross-sectional, questionnaire-based study was conducted with a cohort of 978 U.S. soldiers who screened positive for a deployment-related concussion upon returning from Iraq or Afghanistan. The details of the screening process and a description of the headaches in this same cohort have been previously reported.^[5] All soldiers underwent a clinical evaluation at the Madigan Traumatic Brain Injury Program that included a history, physical examination, 13-item self-administered headache questionnaire, and a battery of cognitive and psychological assessments as described previously. Information about head trauma was obtained by interviewing the soldier and reviewing theater medical records. The Madigan Redeployment Evaluation of Concussion (MREC) test, scored from 0 to 30 with below 25 defined as abnormal, was used to assess cognitive function. The MREC, which is similar to the Military Acute Concussion Evaluation (http://www.dvbic.org/images/pdfs/providers/MACE-Information-Paper-V3.aspx), is a neurocognitive screening instrument intended for evaluating soldiers with a deployment-related concussion after returning stateside. Posttraumatic stress disorder (PTSD) symptoms were assessed using the PTSD symptom checklist, military version (PCL). A global measure of acute traumatic brain injury (TBI) symptoms at the time of the injury was obtained using the 2-plus-10 questionnaire.^[5] The 2-plus-10 questionnaire consists of an initial 2-question followed by a 10-question screen if the soldier answers yes to either of the first 2 questions. This questionnaire is scored in a standardized manner from 0 to 39; the score from the 2-plus-10 questionnaire will herein be called the TBI Score.^[5] Data from soldiers with CDH, defined as headaches occurring 15 or more days per month for the previous 3 months, were compared to soldiers with episodic headaches who had less than 15 headache days per month.

Fisher’s exact test was used to test for differences in proportions, and unpaired t-test was used to test for differences in ordinal variables with a normal distribution. Correlation coefficients were calculated to test the relationship between individual variables where appropriate. P values less than .05 were considered significant.

Results

Nine hundred fifty-seven of 978 soldiers with a deployment-related concussion reported headaches in the preceding 3 months. One hundred ninety-six soldiers (20%) reported 15 or more headache days per month for the previous 3 months and thereby met criteria for CDH (Table 1). Soldiers with CDH had a median of 26.7 headache days per month, and the headache syndrome had been present for a median of 11.5 months. Forty-six (23%) of the soldiers with CDH reported headaches on 90 of the previous 90 days. One hundred seven (55%) soldiers with CDH had headaches that began within 1 week of head trauma and thereby met the time criterion for posttraumatic headache (PTHA). In comparison, 33% of episodic headaches had onset within 1 week of a concussion (P < .0001). Soldiers with CDH used abortive headache medications an average of 15.1 days per month compared to 3.3 days per month for soldiers with episodic headache (P < .0001). Ninety-seven (49%) soldiers with CDH used abortive headache medications on 15 or more days per month for the previous 3 months (P < .05).

Discussion

This study examined CDH in a large cohort of returning U.S. Army soldiers who had a deployment-related concussion. We found that 20% of soldiers with a history of concussion had headaches manifesting as CDH. When one considers prevalence rates of CDH of 4–5% in the general population,^[6,7] the prevalence of CDH in soldiers after a deployment-related concussion is 4− to 5-fold higher. The high prevalence of CDH in soldiers after concussion is consistent with previous studies suggesting a role for mild head trauma in the development of CDH. In a U.S. population sample, 20% of males with CDH reported a preceding head or neck injury.^[8] We previously reported that one third of soldiers with a history of head or neck trauma referred to a military headache clinic had CDH.^[9]

Head trauma can trigger new headaches and/or can exacerbate preexisting primary headaches. When new headaches develop within 1 week after head trauma, they are classified as posttraumatic headaches according to ICHD-2.^[10] Compared to episodic headache, we found that CDH was significantly associated with headache onset within a week of the concussive event. Soldiers with CDH were 1.7-fold more likely to have headaches meeting ICHD-2 criteria for PTHA compared to soldiers with episodic headaches. This finding further supports trauma as a triggering event in the development of CDH. Given the increased propensity of posttraumatic headaches to manifest as CDH, interventions administered early after injury that prevent headache chronification may be beneficial. It may be more effective to prevent the development of CDH early after injury than to treat established CDH.

Migraine was the headache phenotype in 66% of soldiers with CDH in our study, with an additional 28% having multiple features of migraine. Migraine headaches were significantly more common in soldiers with CDH compared to those with episodic headache. In a headache clinic-based population, migraine was the headache phenotype in over 90% of soldiers with posttraumatic headache, over half of whom had CDH.^[11] In comparison, the prevalence of chronic migraine is 2% in the general U.S. population and 4% in Army soldiers post-deployment.^[12,13] These findings support a strong association between concussion and chronic migraine in U.S. service members. Chronic migraine should be regarded as the predominant headache syndrome among soldiers with posttraumatic CDH.

Topiramate and botulinum toxin are the only treatments that have been shown to be effective for chronic migraine in the general population.^[14] It remains to be determined if these treatments are also effective for posttraumatic chronic migraine. In an uncontrolled observational study, topiramate was associated with headache improvement in soldiers with chronic PTHA, many of whom had posttraumatic chronic migraine.^[11] Identifying effective therapies for posttraumatic chronic migraine is an important goal of future research.

Exposure to an explosive blast was the mechanism of concussive injury in over 80% of soldiers in our study, similar to findings reported by other studies of service members deployed to Iraq or Afghanistan.^[2–4,15] The potential mechanisms of blast-induced neurotrauma are complex and may include primary effects from the blast wave, secondary effects caused by fragments or debris, tertiary effects of rapid acceleration and deceleration, flash burns, and effects of inhalation of toxic gases.^[16,17] We found no differences in blast exposures between soldiers with CDH compared to those with episodic headaches. Likewise, in a clinic-based population, headache frequency was found to be similar between soldiers with blast-related concussion and non-blast causes of concussion. Wilk et al recently reported that blast mechanism was associated with persistence of headaches and tinnitus at 3 to 6 months in soldiers with concussion and loss of consciousness.^[18] The available information suggests that while blast injury increases the likelihood of developing chronic headaches that persist beyond 3 months after injury, it does not appear to affect the frequency of headaches as compared to other mechanisms of concussion.

An important question is whether the severity of head trauma or repetitive head injuries increases the risk of CDH. Couch et al found an association between multiple head and neck traumas and CDH in the general population.^[8] We did not find significant differences in the total number of concussions or the number of concussions resulting in loss of consciousness between soldiers with CDH and episodic headaches. Soldiers with CDH did report more symptoms immediately after the concussion, as measured by the TBI score, suggesting that they may have experienced a more acutely symptomatic injury and perhaps, by extension, a potentially more severe concussion. This is a tenuous assertion that requires validation by prospective studies because of the high likelihood of recall bias.

Psychological trauma and posttraumatic stress may be significant mediators of headache chronicity after head trauma. In support of this, we found that soldiers with CDH had more symptoms of PTSD and were more than twice as likely to screen positive for PTSD compared to soldiers with episodic headaches. Indeed, 41% of soldiers with CDH had a positive screen for PTSD. Additionally, PCL scores were significantly correlated to the number of headache days and blast exposures. Studies in civilian and military populations have demonstrated an association between PTSD and an increased frequency of headache.^[19,20] Bryan et al, using regression modeling, found a statistically significant association between PTSD symptoms and headache severity in veterans of the wars in Iraq and Afghanistan.^[21]

The extent to which symptoms of the post-concussive syndrome after mild head injury can be attributed to PTSD or depression in returning U.S. service members remains a topic of significant debate.^[22,23] In a pivotal study by Hoge et al, after controlling for PTSD and depression, headache was the only symptom significantly associated with mild concussion in 2525 U.S. Army infantry soldiers screened 3–4 months after return from a 1 year deployment to Iraq.^[2] Thus, while posttraumatic stress may magnify the frequency and severity of headaches, it does not appear to be the proximate cause of headaches in this population. The observed high prevalence of PTSD in our study cohort, particularly among soldiers with CDH, reinforces the importance of screening soldiers and veterans for PTSD and, when positive, referring them for behavioral health evaluation and treatment.

Another important factor that can contribute to headache chronification is overuse of acute analgesic medications resulting in medication overuse headache (MOH). Medication overuse has been implicated in transforming episodic migraine to chronic migraine.^[24] Medication overuse is defined as use of abortive headache medication on 15 or more days per month for 3 or more months.^[10] Nearly half (49%) of soldiers with CDH in our study met criteria for possible MOH. The majority, 80% or more, of soldiers in this cohort used nonsteroidal anti-inflammatory agents and acetaminophen as abortive headache medications.^[5] We may have underestimated possible MOH in the proportion of soldiers using prescription medications such as triptans or narcotics (less than 10% of soldiers in this cohort)^[5] or combination analgesics such as acetaminophen–aspirin–caffeine (6% of soldiers in this cohort)^[5] given the lower threshold of medication days per month associated with MOH with use of these medications. A diagnosis of definite MOH requires resolution of headaches following cessation of the overused analgesics medication(s). Thus, it is not possible to determine precisely the proportion of subjects in our study who had definite MOH. Avoiding medication overuse in the first place and identifying and addressing MOH when it develops are strategies that may decrease the development of CDH in soldiers following a concussion.

This study has many limitations related to the questionnaire-based, cross-sectional design. Headache frequency was retrospectively reported by soldiers and was not prospectively recorded in a headache log. It is possible that recall errors in reporting headache frequency resulted in misclassification of some soldiers with regard to having CDH or episodic headache. Likewise, reporting of blast exposures and acute symptoms of concussion that may have occurred many months ago are subject to recall error. Screening for preexisting headaches was not performed, potentially contributing to misattribution and making an analysis of incident headaches vs worsening of previous headache syndromes impossible. While all soldiers met screening criteria for a deployment-related concussion, concussion severity was not determined, thereby limiting any conclusions regarding concussion severity and headache chronicity drawn from this study. Theater records were used to validate some of these events but were not available in all cases. Soldiers in the study were evaluated at a TBI clinic, and this type of setting may have inclined them to over-report symptoms. Finally, this study may not be representative of all U.S. service-members with a deployment-related concussion as it was conducted at a single U.S. Army installation over a 6-month period.

Conclusions

The prevalence of CDH in U.S. soldiers after a deployment-related concussion is 20%, or 4− to 5-fold higher than that seen in the general population. CDH in soldiers with concussion usually has multiple features of migraine and frequently resembles chronic migraine. Onset of headaches within 1 week of a concussion is associated with the development of CDH as compared to episodic headache. Overuse of headache abortive medications, raising the possibility of MOH, occurs in half of soldiers with CDH. Blast exposure and multiple concussions are common in this population, but these factors are not specifically associated with CDH as compared to episodic headache. PTSD symptoms are strongly associated with CDH suggesting that traumatic stress may be a significant mediator of headache chronicity. These findings justify future studies examining strategies to prevent and treat CDH in military service members.

Study supported by
The Comprehensive National Neuroscience Program at the Uniformed Services University of the Health Sciences by a grant from the Congressionally Directed Medical Research Program.

Disclaimer
The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.