Traumatic Brain Injury

A series of three studies in college students showed that some serum markers are associated with concussion but the background level of the markers can vary considerably. There was no association between the markers and history of concussion, and they markers varied significantly by sex and race.

jpbcpa/Getty Images

The work, published in Neurology, suggests that there is hope for finding biomarkers for concussion, but much more work needs to be done.

Serum levels of amyloid beta 42 (Abeta42), total tau, and S100 calcium binding protein B (S100B) were associated with concussion, especially when tests were performed within 4 hours of the injury. However, the varying background levels indicate that these biomarkers are not yet ready for clinical application.

All three studies looked at serum levels of Abeta42, total tau, S100B, ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), microtubule-associated protein 2 (MAP2), and 2’,3’-cyclic-nucleotide 3’-phosphodiesterase (CNPase).

In the first study, researchers recruited 415 college athletes without a concussion (61% male, 40% white). The researchers took measurements outside of the athletes’ competitive sports season to maximize the odds that the levels would represent a true baseline. The median time between blood draw and the last risk of head impact was 80 days (mean, 98.4 days; interquartile range, 38-204 days).

Males had higher levels of UCH-L1 (Cohen d = 0.75; P less than .001) and S100B (Cohen d = 0.56; P less than .001), while females had higher levels of CNPase (Cohen d = 0.43; P less than .001). White subjects had higher levels of Abeta42 (Cohen d = .28; P = .005) and CNPase (Cohen d = 0.46; P less than .001). Black subjects had higher levels of UCH-L1 (Cohen d = 0.61; P less than .001) and S100 B (Cohen d = 1.1; P less than .001).

The measurements were not particularly reliable, with retests over 6- to 12-month periods yielding varying results such that none of the test/retest cutoff points reached the cutoff for acceptable reliability.

The second study was an observational cohort study of the same 415 subjects. The researchers assessed the self-reported concussion history and the cumulative exposure to collision sports with serum levels of the above biomarkers. The only relationship between a biomarker history and self-reported concussions was higher baseline Abeta42, but that had a small effect size (P = .005). Among football players, there was no association between approximate number of head impacts and any baseline biomarker.

The third study looked at 31 subjects who had experienced a sports-related concussion, 29 of whom had had both a baseline and a postconcussion blood draw, and compared them with nonconcussed, demographically matched athletes.

Of all the biomarkers studied, only levels of S100B rose following a concussion, with 67% of concussed subjects experiencing such a change (P = .003). When the researchers restricted the analysis to subjects who had a blood draw within 4 hours of the concussion, 88% of the tests showed an increase (P = .001). UCH-L1 also rose in 86% of subjects, but this change was not significant after adjustment for multiple comparisons (P greater than .007).

Compared with controls, concussed individuals had significantly higher levels of Abeta42, total tau, S100B, and GFAP. Of the concussed patients, 79.4% had Abeta42 levels higher than the median of controls, 67.6% had higher levels of total tau than the median of controls, and 83.3% had higher levels of S100B. Restriction of analysis to blood drawn within 4 hours of the injury yielded values of 81.3%, 75.0%, and 88.2%, respectively.

When limited to blood draws taken within 4 hours of injury, the researchers found fair diagnostic accuracy for measurements of Abeta42 (area under the curve, 0.75; 95% confidence interval, 0.59-0.91), total tau (AUC, 0.74; 95% CI, 0.58-0.90), and S100B (AUC, 0.75; 95% CI, 0.64-0.85). Abeta42 concentrations higher than 13.7 pg/mL were 75.0% sensitive and 82.4% specific to a sports-related concussion. Total tau concentrations higher than 1.7 pg/mL detected sports-related concussions at 75.0% sensitivity and 66.3% specificity, with acceptable diagnostic accuracy for white subjects (AUC, 0.82, 95% CI, 0.72-0.93). Also for white participants, S100B concentrations higher than 53 pg/mL predicted sports-related concussions with 83.3% sensitivity and 74.6% specificity.

The researchers found no associations between biomarkers and performance on clinical tests or time away from sports.

SOURCE: BM Asken et al. Neurology. 2018. doi: 10.1212/WNL.0000000000006613.

A series of three studies in college students showed that some serum markers are associated with concussion but the background level of the markers can vary considerably. There was no association between the markers and history of concussion, and they markers varied significantly by sex and race.

jpbcpa/Getty Images

The work, published in Neurology, suggests that there is hope for finding biomarkers for concussion, but much more work needs to be done.

Serum levels of amyloid beta 42 (Abeta42), total tau, and S100 calcium binding protein B (S100B) were associated with concussion, especially when tests were performed within 4 hours of the injury. However, the varying background levels indicate that these biomarkers are not yet ready for clinical application.

All three studies looked at serum levels of Abeta42, total tau, S100B, ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), microtubule-associated protein 2 (MAP2), and 2’,3’-cyclic-nucleotide 3’-phosphodiesterase (CNPase).

In the first study, researchers recruited 415 college athletes without a concussion (61% male, 40% white). The researchers took measurements outside of the athletes’ competitive sports season to maximize the odds that the levels would represent a true baseline. The median time between blood draw and the last risk of head impact was 80 days (mean, 98.4 days; interquartile range, 38-204 days).

Males had higher levels of UCH-L1 (Cohen d = 0.75; P less than .001) and S100B (Cohen d = 0.56; P less than .001), while females had higher levels of CNPase (Cohen d = 0.43; P less than .001). White subjects had higher levels of Abeta42 (Cohen d = .28; P = .005) and CNPase (Cohen d = 0.46; P less than .001). Black subjects had higher levels of UCH-L1 (Cohen d = 0.61; P less than .001) and S100 B (Cohen d = 1.1; P less than .001).

The measurements were not particularly reliable, with retests over 6- to 12-month periods yielding varying results such that none of the test/retest cutoff points reached the cutoff for acceptable reliability.

The second study was an observational cohort study of the same 415 subjects. The researchers assessed the self-reported concussion history and the cumulative exposure to collision sports with serum levels of the above biomarkers. The only relationship between a biomarker history and self-reported concussions was higher baseline Abeta42, but that had a small effect size (P = .005). Among football players, there was no association between approximate number of head impacts and any baseline biomarker.

The third study looked at 31 subjects who had experienced a sports-related concussion, 29 of whom had had both a baseline and a postconcussion blood draw, and compared them with nonconcussed, demographically matched athletes.

Of all the biomarkers studied, only levels of S100B rose following a concussion, with 67% of concussed subjects experiencing such a change (P = .003). When the researchers restricted the analysis to subjects who had a blood draw within 4 hours of the concussion, 88% of the tests showed an increase (P = .001). UCH-L1 also rose in 86% of subjects, but this change was not significant after adjustment for multiple comparisons (P greater than .007).

Compared with controls, concussed individuals had significantly higher levels of Abeta42, total tau, S100B, and GFAP. Of the concussed patients, 79.4% had Abeta42 levels higher than the median of controls, 67.6% had higher levels of total tau than the median of controls, and 83.3% had higher levels of S100B. Restriction of analysis to blood drawn within 4 hours of the injury yielded values of 81.3%, 75.0%, and 88.2%, respectively.

When limited to blood draws taken within 4 hours of injury, the researchers found fair diagnostic accuracy for measurements of Abeta42 (area under the curve, 0.75; 95% confidence interval, 0.59-0.91), total tau (AUC, 0.74; 95% CI, 0.58-0.90), and S100B (AUC, 0.75; 95% CI, 0.64-0.85). Abeta42 concentrations higher than 13.7 pg/mL were 75.0% sensitive and 82.4% specific to a sports-related concussion. Total tau concentrations higher than 1.7 pg/mL detected sports-related concussions at 75.0% sensitivity and 66.3% specificity, with acceptable diagnostic accuracy for white subjects (AUC, 0.82, 95% CI, 0.72-0.93). Also for white participants, S100B concentrations higher than 53 pg/mL predicted sports-related concussions with 83.3% sensitivity and 74.6% specificity.

The researchers found no associations between biomarkers and performance on clinical tests or time away from sports.

SOURCE: BM Asken et al. Neurology. 2018. doi: 10.1212/WNL.0000000000006613.

A series of three studies in college students showed that some serum markers are associated with concussion but the background level of the markers can vary considerably. There was no association between the markers and history of concussion, and they markers varied significantly by sex and race.

jpbcpa/Getty Images

The work, published in Neurology, suggests that there is hope for finding biomarkers for concussion, but much more work needs to be done.

Serum levels of amyloid beta 42 (Abeta42), total tau, and S100 calcium binding protein B (S100B) were associated with concussion, especially when tests were performed within 4 hours of the injury. However, the varying background levels indicate that these biomarkers are not yet ready for clinical application.

All three studies looked at serum levels of Abeta42, total tau, S100B, ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), microtubule-associated protein 2 (MAP2), and 2’,3’-cyclic-nucleotide 3’-phosphodiesterase (CNPase).

In the first study, researchers recruited 415 college athletes without a concussion (61% male, 40% white). The researchers took measurements outside of the athletes’ competitive sports season to maximize the odds that the levels would represent a true baseline. The median time between blood draw and the last risk of head impact was 80 days (mean, 98.4 days; interquartile range, 38-204 days).

Males had higher levels of UCH-L1 (Cohen d = 0.75; P less than .001) and S100B (Cohen d = 0.56; P less than .001), while females had higher levels of CNPase (Cohen d = 0.43; P less than .001). White subjects had higher levels of Abeta42 (Cohen d = .28; P = .005) and CNPase (Cohen d = 0.46; P less than .001). Black subjects had higher levels of UCH-L1 (Cohen d = 0.61; P less than .001) and S100 B (Cohen d = 1.1; P less than .001).

The measurements were not particularly reliable, with retests over 6- to 12-month periods yielding varying results such that none of the test/retest cutoff points reached the cutoff for acceptable reliability.

The second study was an observational cohort study of the same 415 subjects. The researchers assessed the self-reported concussion history and the cumulative exposure to collision sports with serum levels of the above biomarkers. The only relationship between a biomarker history and self-reported concussions was higher baseline Abeta42, but that had a small effect size (P = .005). Among football players, there was no association between approximate number of head impacts and any baseline biomarker.

The third study looked at 31 subjects who had experienced a sports-related concussion, 29 of whom had had both a baseline and a postconcussion blood draw, and compared them with nonconcussed, demographically matched athletes.

Of all the biomarkers studied, only levels of S100B rose following a concussion, with 67% of concussed subjects experiencing such a change (P = .003). When the researchers restricted the analysis to subjects who had a blood draw within 4 hours of the concussion, 88% of the tests showed an increase (P = .001). UCH-L1 also rose in 86% of subjects, but this change was not significant after adjustment for multiple comparisons (P greater than .007).

Compared with controls, concussed individuals had significantly higher levels of Abeta42, total tau, S100B, and GFAP. Of the concussed patients, 79.4% had Abeta42 levels higher than the median of controls, 67.6% had higher levels of total tau than the median of controls, and 83.3% had higher levels of S100B. Restriction of analysis to blood drawn within 4 hours of the injury yielded values of 81.3%, 75.0%, and 88.2%, respectively.

When limited to blood draws taken within 4 hours of injury, the researchers found fair diagnostic accuracy for measurements of Abeta42 (area under the curve, 0.75; 95% confidence interval, 0.59-0.91), total tau (AUC, 0.74; 95% CI, 0.58-0.90), and S100B (AUC, 0.75; 95% CI, 0.64-0.85). Abeta42 concentrations higher than 13.7 pg/mL were 75.0% sensitive and 82.4% specific to a sports-related concussion. Total tau concentrations higher than 1.7 pg/mL detected sports-related concussions at 75.0% sensitivity and 66.3% specificity, with acceptable diagnostic accuracy for white subjects (AUC, 0.82, 95% CI, 0.72-0.93). Also for white participants, S100B concentrations higher than 53 pg/mL predicted sports-related concussions with 83.3% sensitivity and 74.6% specificity.

The researchers found no associations between biomarkers and performance on clinical tests or time away from sports.

SOURCE: BM Asken et al. Neurology. 2018. doi: 10.1212/WNL.0000000000006613.

The CDC has developed a guideline for the diagnosis and management of mild traumatic brain injury (mTBI) in children. The guideline was published online ahead of print September 4 in JAMA Pediatrics. To support the “multifaceted approach” that the authors recommend for implementing the guideline, the CDC has created materials such as a screening tool, online training, fact sheets, patient discharge instructions, and symptom-based recovery tips.

The number of emergency department visits for mTBI has increased significantly during the past decade, said the authors, yet no evidence-based clinical guidelines had been drafted in the United States to guide the diagnosis, prognosis, and management of this condition. To fill this gap, the CDC established the Pediatric mTBI Guideline Workgroup, which drafted recommendations based on a systematic review of research published from January 1990 through July 2015.

Diagnosis

The first section of the guideline offers recommendations for diagnosis. Health care professionals should not routinely obtain head CT in children with suspected mTBI, say the authors. They should, however, use validated clinical decision rules to identify children with mTBI at low risk for intracranial injury in whom CT is not indicated, as well as children at higher risk for intracranial injury for whom CT may be warranted. The authors cite the Pediatric Emergency Care Applied Research Network (PECARN) decision rules as an example.

Furthermore, health care professionals should not routinely use brain MRI to evaluate suspected or diagnosed mTBI in children, according to the guideline. No study examining whether this imaging technique is appropriate met the workgroup’s inclusion criteria.

An age-appropriate, validated symptom rating scale should be one component of the diagnostic evaluation, say the authors. The Standardized Assessment of Concussion, however, “should not be exclusively used to diagnose mTBI in children aged 6 to 18,” they add. Finally, the guideline discourages the use of biomarkers (ie, serum markers) for diagnosis outside of a research setting.

Prognosis

The second section of the document provides guidance on developing a prognosis. Clinicians should advise patients and their families that most children with mTBI do not have significant difficulties that last for more than one to three months after injury, say the authors. They also should state that even though certain factors predict a child’s risk for prolonged symptoms, “each child’s recovery from mTBI is unique and will follow its own trajectory.”

Health care professionals should evaluate a child’s premorbid history as soon as possible to help determine the prognosis, say the authors. Children and families should be advised that factors such as history of mTBI, lower cognitive ability, and neurologic disorder can delay recovery from mTBI. Clinicians should screen for known risk factors for persistent symptoms and use a combination of tools (eg, validated symptom scales, cognitive testing, and balance testing) to assess recovery, according to the guideline.

Children with mTBI at high risk for persistent symptoms should be monitored closely. “For children with mTBI whose symptoms do not resolve as expected with standard care (ie, within four to six weeks), health care professionals should provide or refer for appropriate assessments and interventions,” say the authors.

Management and Treatment

The guideline’s section devoted to management and treatment begins with recommendations for returning to normal activities. Clinicians should recommend restricting physical and cognitive activity during the first several days after pediatric mTBI, according to the authors. After that point, doctors should advise patients and families “to resume a gradual schedule of activity that does not exacerbate symptoms, with close monitoring of symptom expression.” If the patient completes this step successfully, the clinician should offer an active rehabilitation program that progressively reintroduces noncontact aerobic activity that does not worsen symptoms. The number and severity of symptoms should be monitored closely throughout the patient’s recovery. A patient should resume full activity when his or her performance returns to its premorbid level, provided that he or she has no symptoms at rest or with increasing levels of exertion, according to the guideline.

“To assist children returning to school after mTBI, medical and school-based teams should counsel the student and family regarding the process of gradually increasing the duration and intensity of academic activities as tolerated, with the goal of increasing participation without significantly exacerbating symptoms,” say the authors. Return-to-school protocols should be adapted to the severity of the child’s postconcussion symptoms. School personnel should assess the need for additional educational support in students with prolonged symptoms that harm their academic performance, according to the guideline.

If a child with mTBI develops severe headache, especially if the headache is associated with other risk factors or has worsened after mTBI, emergency department professionals should observe him or her and consider obtaining a head CT to evaluate for intracranial injury, say the authors. Health care professionals should explain proper sleep hygiene to all patients with mTBI and their families to facilitate recovery.

If a child with mTBI has cognitive dysfunction, clinicians should attempt to determine its etiology within the context of other mTBI symptoms, say the authors. Treatment for cognitive dysfunction should reflect its presumed etiology, they conclude.

—Erik Greb

Suggested Reading

Lumba-Brown A, Yeates KO, Sarmiento K, et al. Centers for Disease Control and Prevention guideline on the diagnosis and management of mild traumatic brain injury among children. JAMA Pediatr. 2018 Sep 4 [Epub ahead of print].

Lumba-Brown A, Yeates KO, Sarmiento K, et al. Diagnosis and management of mild traumatic brain injury in children: a systematic review. JAMA Pediatr. 2018 Sep 4 [Epub ahead of print].

McCrea M, Manley G. State of the science on pediatric mild traumatic brain injury: progress toward clinical translation. JAMA Pediatr. 2018 Sep 4 [Epub ahead of print].

The CDC has developed a guideline for the diagnosis and management of mild traumatic brain injury (mTBI) in children. The guideline was published online ahead of print September 4 in JAMA Pediatrics. To support the “multifaceted approach” that the authors recommend for implementing the guideline, the CDC has created materials such as a screening tool, online training, fact sheets, patient discharge instructions, and symptom-based recovery tips.

The number of emergency department visits for mTBI has increased significantly during the past decade, said the authors, yet no evidence-based clinical guidelines had been drafted in the United States to guide the diagnosis, prognosis, and management of this condition. To fill this gap, the CDC established the Pediatric mTBI Guideline Workgroup, which drafted recommendations based on a systematic review of research published from January 1990 through July 2015.

Diagnosis

The first section of the guideline offers recommendations for diagnosis. Health care professionals should not routinely obtain head CT in children with suspected mTBI, say the authors. They should, however, use validated clinical decision rules to identify children with mTBI at low risk for intracranial injury in whom CT is not indicated, as well as children at higher risk for intracranial injury for whom CT may be warranted. The authors cite the Pediatric Emergency Care Applied Research Network (PECARN) decision rules as an example.

Furthermore, health care professionals should not routinely use brain MRI to evaluate suspected or diagnosed mTBI in children, according to the guideline. No study examining whether this imaging technique is appropriate met the workgroup’s inclusion criteria.

An age-appropriate, validated symptom rating scale should be one component of the diagnostic evaluation, say the authors. The Standardized Assessment of Concussion, however, “should not be exclusively used to diagnose mTBI in children aged 6 to 18,” they add. Finally, the guideline discourages the use of biomarkers (ie, serum markers) for diagnosis outside of a research setting.

Prognosis

The second section of the document provides guidance on developing a prognosis. Clinicians should advise patients and their families that most children with mTBI do not have significant difficulties that last for more than one to three months after injury, say the authors. They also should state that even though certain factors predict a child’s risk for prolonged symptoms, “each child’s recovery from mTBI is unique and will follow its own trajectory.”

Health care professionals should evaluate a child’s premorbid history as soon as possible to help determine the prognosis, say the authors. Children and families should be advised that factors such as history of mTBI, lower cognitive ability, and neurologic disorder can delay recovery from mTBI. Clinicians should screen for known risk factors for persistent symptoms and use a combination of tools (eg, validated symptom scales, cognitive testing, and balance testing) to assess recovery, according to the guideline.

Children with mTBI at high risk for persistent symptoms should be monitored closely. “For children with mTBI whose symptoms do not resolve as expected with standard care (ie, within four to six weeks), health care professionals should provide or refer for appropriate assessments and interventions,” say the authors.

Management and Treatment

The guideline’s section devoted to management and treatment begins with recommendations for returning to normal activities. Clinicians should recommend restricting physical and cognitive activity during the first several days after pediatric mTBI, according to the authors. After that point, doctors should advise patients and families “to resume a gradual schedule of activity that does not exacerbate symptoms, with close monitoring of symptom expression.” If the patient completes this step successfully, the clinician should offer an active rehabilitation program that progressively reintroduces noncontact aerobic activity that does not worsen symptoms. The number and severity of symptoms should be monitored closely throughout the patient’s recovery. A patient should resume full activity when his or her performance returns to its premorbid level, provided that he or she has no symptoms at rest or with increasing levels of exertion, according to the guideline.

“To assist children returning to school after mTBI, medical and school-based teams should counsel the student and family regarding the process of gradually increasing the duration and intensity of academic activities as tolerated, with the goal of increasing participation without significantly exacerbating symptoms,” say the authors. Return-to-school protocols should be adapted to the severity of the child’s postconcussion symptoms. School personnel should assess the need for additional educational support in students with prolonged symptoms that harm their academic performance, according to the guideline.

If a child with mTBI develops severe headache, especially if the headache is associated with other risk factors or has worsened after mTBI, emergency department professionals should observe him or her and consider obtaining a head CT to evaluate for intracranial injury, say the authors. Health care professionals should explain proper sleep hygiene to all patients with mTBI and their families to facilitate recovery.

If a child with mTBI has cognitive dysfunction, clinicians should attempt to determine its etiology within the context of other mTBI symptoms, say the authors. Treatment for cognitive dysfunction should reflect its presumed etiology, they conclude.

—Erik Greb

Suggested Reading

Lumba-Brown A, Yeates KO, Sarmiento K, et al. Centers for Disease Control and Prevention guideline on the diagnosis and management of mild traumatic brain injury among children. JAMA Pediatr. 2018 Sep 4 [Epub ahead of print].

Lumba-Brown A, Yeates KO, Sarmiento K, et al. Diagnosis and management of mild traumatic brain injury in children: a systematic review. JAMA Pediatr. 2018 Sep 4 [Epub ahead of print].

McCrea M, Manley G. State of the science on pediatric mild traumatic brain injury: progress toward clinical translation. JAMA Pediatr. 2018 Sep 4 [Epub ahead of print].

The CDC has developed a guideline for the diagnosis and management of mild traumatic brain injury (mTBI) in children. The guideline was published online ahead of print September 4 in JAMA Pediatrics. To support the “multifaceted approach” that the authors recommend for implementing the guideline, the CDC has created materials such as a screening tool, online training, fact sheets, patient discharge instructions, and symptom-based recovery tips.

The number of emergency department visits for mTBI has increased significantly during the past decade, said the authors, yet no evidence-based clinical guidelines had been drafted in the United States to guide the diagnosis, prognosis, and management of this condition. To fill this gap, the CDC established the Pediatric mTBI Guideline Workgroup, which drafted recommendations based on a systematic review of research published from January 1990 through July 2015.

Diagnosis

The first section of the guideline offers recommendations for diagnosis. Health care professionals should not routinely obtain head CT in children with suspected mTBI, say the authors. They should, however, use validated clinical decision rules to identify children with mTBI at low risk for intracranial injury in whom CT is not indicated, as well as children at higher risk for intracranial injury for whom CT may be warranted. The authors cite the Pediatric Emergency Care Applied Research Network (PECARN) decision rules as an example.

Furthermore, health care professionals should not routinely use brain MRI to evaluate suspected or diagnosed mTBI in children, according to the guideline. No study examining whether this imaging technique is appropriate met the workgroup’s inclusion criteria.

An age-appropriate, validated symptom rating scale should be one component of the diagnostic evaluation, say the authors. The Standardized Assessment of Concussion, however, “should not be exclusively used to diagnose mTBI in children aged 6 to 18,” they add. Finally, the guideline discourages the use of biomarkers (ie, serum markers) for diagnosis outside of a research setting.

Prognosis

The second section of the document provides guidance on developing a prognosis. Clinicians should advise patients and their families that most children with mTBI do not have significant difficulties that last for more than one to three months after injury, say the authors. They also should state that even though certain factors predict a child’s risk for prolonged symptoms, “each child’s recovery from mTBI is unique and will follow its own trajectory.”

Health care professionals should evaluate a child’s premorbid history as soon as possible to help determine the prognosis, say the authors. Children and families should be advised that factors such as history of mTBI, lower cognitive ability, and neurologic disorder can delay recovery from mTBI. Clinicians should screen for known risk factors for persistent symptoms and use a combination of tools (eg, validated symptom scales, cognitive testing, and balance testing) to assess recovery, according to the guideline.

Children with mTBI at high risk for persistent symptoms should be monitored closely. “For children with mTBI whose symptoms do not resolve as expected with standard care (ie, within four to six weeks), health care professionals should provide or refer for appropriate assessments and interventions,” say the authors.

Management and Treatment

The guideline’s section devoted to management and treatment begins with recommendations for returning to normal activities. Clinicians should recommend restricting physical and cognitive activity during the first several days after pediatric mTBI, according to the authors. After that point, doctors should advise patients and families “to resume a gradual schedule of activity that does not exacerbate symptoms, with close monitoring of symptom expression.” If the patient completes this step successfully, the clinician should offer an active rehabilitation program that progressively reintroduces noncontact aerobic activity that does not worsen symptoms. The number and severity of symptoms should be monitored closely throughout the patient’s recovery. A patient should resume full activity when his or her performance returns to its premorbid level, provided that he or she has no symptoms at rest or with increasing levels of exertion, according to the guideline.

“To assist children returning to school after mTBI, medical and school-based teams should counsel the student and family regarding the process of gradually increasing the duration and intensity of academic activities as tolerated, with the goal of increasing participation without significantly exacerbating symptoms,” say the authors. Return-to-school protocols should be adapted to the severity of the child’s postconcussion symptoms. School personnel should assess the need for additional educational support in students with prolonged symptoms that harm their academic performance, according to the guideline.

If a child with mTBI develops severe headache, especially if the headache is associated with other risk factors or has worsened after mTBI, emergency department professionals should observe him or her and consider obtaining a head CT to evaluate for intracranial injury, say the authors. Health care professionals should explain proper sleep hygiene to all patients with mTBI and their families to facilitate recovery.

If a child with mTBI has cognitive dysfunction, clinicians should attempt to determine its etiology within the context of other mTBI symptoms, say the authors. Treatment for cognitive dysfunction should reflect its presumed etiology, they conclude.

—Erik Greb

Suggested Reading

Lumba-Brown A, Yeates KO, Sarmiento K, et al. Centers for Disease Control and Prevention guideline on the diagnosis and management of mild traumatic brain injury among children. JAMA Pediatr. 2018 Sep 4 [Epub ahead of print].

Lumba-Brown A, Yeates KO, Sarmiento K, et al. Diagnosis and management of mild traumatic brain injury in children: a systematic review. JAMA Pediatr. 2018 Sep 4 [Epub ahead of print].

McCrea M, Manley G. State of the science on pediatric mild traumatic brain injury: progress toward clinical translation. JAMA Pediatr. 2018 Sep 4 [Epub ahead of print].

Residents of Denmark who seek medical attention for traumatic brain injury (TBI) have an increased risk of suicide, compared with the general Danish population without TBI, according to a study published in the August 14 issue of JAMA. “Additional analyses revealed that the risk of suicide was higher for individuals with severe TBI, numerous medical contacts, and longer hospital stays,” said lead author Trine Madsen, PhD. Individuals were at highest risk in the first six months after discharge, said Dr. Madsen, who is a postdoctoral fellow at the Danish Research Institute for Suicide Prevention in Hellerup.

A history of TBI previously has been associated with higher rates of self-harm, suicide, and death than are found in the general population. However, previous studies have been limited by methodological shortcomings, such as small sample sizes and low numbers of suicide cases with TBI. Dr. Madsen and colleagues conducted a retrospective cohort study using nationwide registers covering 7,418,391 individuals living in Denmark between 1980 and 2014 with 164,265,624 person-years’ follow-up. Of these people, 567,823 (7.6%) had a medical contact for TBI, which included mild TBI (ie, concussion), skull fracture without documented TBI, and severe TBI (ie, head injuries with evidence of structural brain injury).

Of 34,529 individuals who died by suicide, 3,536 (10.2%) had medical contact for TBI, including 2,701 for mild TBI, 174 for skull fracture without documented TBI, and 661 for severe TBI. The absolute suicide rate was 41 per 100,000 person-years among those with TBI versus 20 per 100,000 person-years among those with no diagnosis of TBI. After accounting for relevant covariates such as fractures not involving the skull, psychiatric diagnoses, and deliberate self-harm, the adjusted incidence ratio was 1.90.

This study “provides insights into the underappreciated relationship between TBI and suicide,” said Lee Goldstein, MD, PhD, and Ramon Diaz-Arrastia, MD, PhD, in an accompanying editorial. “The results … point to an important clinical triad—TBI history, recent injury (especially with long hospital stays), and more numerous postinjury medical contacts for TBI—that serves as a red flag for increased suicide risk,” said Dr. Goldstein, who is affiliated with Boston University School of Medicine, and Dr. Diaz-Arrastia, of the University of Pennsylvania’s Perelman School of Medicine in Philadelphia. The results “indicate that increased suicide risk is relevant across all TBI severity levels, including the far more common mild injuries. Clinicians, health care professionals, and mental health practitioners must take notice of this important information.”

—Glenn S. Williams

Suggested Reading

Goldstein L, Diaz-Arrastia R. Traumatic brain injury and risk of suicide. JAMA. 2018;320(6):554-556.

Madsen T, Erlangsen A, Orlovska S, et al. Association between traumatic brain injury and risk of suicide. JAMA. 2018;320(6):580-588.

Residents of Denmark who seek medical attention for traumatic brain injury (TBI) have an increased risk of suicide, compared with the general Danish population without TBI, according to a study published in the August 14 issue of JAMA. “Additional analyses revealed that the risk of suicide was higher for individuals with severe TBI, numerous medical contacts, and longer hospital stays,” said lead author Trine Madsen, PhD. Individuals were at highest risk in the first six months after discharge, said Dr. Madsen, who is a postdoctoral fellow at the Danish Research Institute for Suicide Prevention in Hellerup.

A history of TBI previously has been associated with higher rates of self-harm, suicide, and death than are found in the general population. However, previous studies have been limited by methodological shortcomings, such as small sample sizes and low numbers of suicide cases with TBI. Dr. Madsen and colleagues conducted a retrospective cohort study using nationwide registers covering 7,418,391 individuals living in Denmark between 1980 and 2014 with 164,265,624 person-years’ follow-up. Of these people, 567,823 (7.6%) had a medical contact for TBI, which included mild TBI (ie, concussion), skull fracture without documented TBI, and severe TBI (ie, head injuries with evidence of structural brain injury).

Of 34,529 individuals who died by suicide, 3,536 (10.2%) had medical contact for TBI, including 2,701 for mild TBI, 174 for skull fracture without documented TBI, and 661 for severe TBI. The absolute suicide rate was 41 per 100,000 person-years among those with TBI versus 20 per 100,000 person-years among those with no diagnosis of TBI. After accounting for relevant covariates such as fractures not involving the skull, psychiatric diagnoses, and deliberate self-harm, the adjusted incidence ratio was 1.90.

This study “provides insights into the underappreciated relationship between TBI and suicide,” said Lee Goldstein, MD, PhD, and Ramon Diaz-Arrastia, MD, PhD, in an accompanying editorial. “The results … point to an important clinical triad—TBI history, recent injury (especially with long hospital stays), and more numerous postinjury medical contacts for TBI—that serves as a red flag for increased suicide risk,” said Dr. Goldstein, who is affiliated with Boston University School of Medicine, and Dr. Diaz-Arrastia, of the University of Pennsylvania’s Perelman School of Medicine in Philadelphia. The results “indicate that increased suicide risk is relevant across all TBI severity levels, including the far more common mild injuries. Clinicians, health care professionals, and mental health practitioners must take notice of this important information.”

—Glenn S. Williams

Suggested Reading

Goldstein L, Diaz-Arrastia R. Traumatic brain injury and risk of suicide. JAMA. 2018;320(6):554-556.

Madsen T, Erlangsen A, Orlovska S, et al. Association between traumatic brain injury and risk of suicide. JAMA. 2018;320(6):580-588.

Residents of Denmark who seek medical attention for traumatic brain injury (TBI) have an increased risk of suicide, compared with the general Danish population without TBI, according to a study published in the August 14 issue of JAMA. “Additional analyses revealed that the risk of suicide was higher for individuals with severe TBI, numerous medical contacts, and longer hospital stays,” said lead author Trine Madsen, PhD. Individuals were at highest risk in the first six months after discharge, said Dr. Madsen, who is a postdoctoral fellow at the Danish Research Institute for Suicide Prevention in Hellerup.

A history of TBI previously has been associated with higher rates of self-harm, suicide, and death than are found in the general population. However, previous studies have been limited by methodological shortcomings, such as small sample sizes and low numbers of suicide cases with TBI. Dr. Madsen and colleagues conducted a retrospective cohort study using nationwide registers covering 7,418,391 individuals living in Denmark between 1980 and 2014 with 164,265,624 person-years’ follow-up. Of these people, 567,823 (7.6%) had a medical contact for TBI, which included mild TBI (ie, concussion), skull fracture without documented TBI, and severe TBI (ie, head injuries with evidence of structural brain injury).

Of 34,529 individuals who died by suicide, 3,536 (10.2%) had medical contact for TBI, including 2,701 for mild TBI, 174 for skull fracture without documented TBI, and 661 for severe TBI. The absolute suicide rate was 41 per 100,000 person-years among those with TBI versus 20 per 100,000 person-years among those with no diagnosis of TBI. After accounting for relevant covariates such as fractures not involving the skull, psychiatric diagnoses, and deliberate self-harm, the adjusted incidence ratio was 1.90.

This study “provides insights into the underappreciated relationship between TBI and suicide,” said Lee Goldstein, MD, PhD, and Ramon Diaz-Arrastia, MD, PhD, in an accompanying editorial. “The results … point to an important clinical triad—TBI history, recent injury (especially with long hospital stays), and more numerous postinjury medical contacts for TBI—that serves as a red flag for increased suicide risk,” said Dr. Goldstein, who is affiliated with Boston University School of Medicine, and Dr. Diaz-Arrastia, of the University of Pennsylvania’s Perelman School of Medicine in Philadelphia. The results “indicate that increased suicide risk is relevant across all TBI severity levels, including the far more common mild injuries. Clinicians, health care professionals, and mental health practitioners must take notice of this important information.”

—Glenn S. Williams

Suggested Reading

Goldstein L, Diaz-Arrastia R. Traumatic brain injury and risk of suicide. JAMA. 2018;320(6):554-556.

Madsen T, Erlangsen A, Orlovska S, et al. Association between traumatic brain injury and risk of suicide. JAMA. 2018;320(6):580-588.

Traumatic brain injury might be associated with an increased risk of suicide, according to results published Aug. 14 in JAMA.

In a retrospective cohort study of 7,418,391 Danish individuals, including 34,529 who died by suicide, patients with medical contact for traumatic brain injury (TBI) had increased suicide risk, compared with the general population (adjusted incidence rate ratio [IRR] = 1.90; 95% confidence interval, 1.83-1.97).

Patients were aged 10 years or older, and follow-up was conducted from Jan. 1, 1980, until date of death, emigration from Denmark, or Dec. 31, 2014, whichever came first. Data were obtained from national registries, including the Danish Civil Registration System, the Database for Integrated Labour Market Research, the National Hospital Register, the Psychiatric Central Research Register, and the Cause of Death Register. Associations between the separate registries were possible because of unique identification numbers assigned to every resident of Denmark, wrote Trine Madsen, PhD, of the Danish Research Institute of Suicide Prevention at the Mental Health Centre Copenhagen, Capital Region of Denmark, and her coauthors.

TBI was recorded in the National Patient Register and was categorized into three types of injury: mild TBI (concussion), skull fracture without documented TBI, and severe TBI (head injury with evidence of structural brain injury). The number of medical contacts for distinct TBI events, accumulated number of days in hospital treatment, age at first TBI, and time since last medical contact for TBI also were assessed.

Data on psychiatric illness and nonfatal self-harm were obtained from the Psychiatric Central Research Register, because of their association with suicide. Data for deaths by suicide were obtained from the Cause of Death Register. Demographic data collected from other registries included sex, age, marital status, cohabitation status, education, and socioeconomic status. IRRs were calculated using adjusted Poisson regression models.

Of 7,418,391 residents of Denmark included in the follow-up period from 1980 to 2014; 567,823 had a TBI diagnosis. Dr. Madsen and her coauthors also found that 423,502 patients (5.7%) were diagnosed with mild TBI, 24,221 (0.3%) with skull fracture, and 120,100 (1.6%) with severe TBI. A total of 34,529 died by suicide.

Of those who died by suicide, 3,536 (10.2%) had a previous TBI diagnosis (2,701 with mild TBI, 174 with skull fracture, and 661 with severe TBI). The absolute rate of suicide in individuals with hospital contact for TBI was 40.6 per 100,000 person-years (95% CI, 39.2-41.9), compared with 19.9 per 100,000 person-years (95% CI, 19.7-20.1) in those with no hospital contact for TBI.

The fully adjusted analysis showed an IRR of 1.90 (95% CI, 1.83-1.97), as well as an increased risk of suicide by TBI severity. The absolute rate for mild TBI was 38.6 per 100,000 person-years (95% CI, 37.1-40.0) with an IRR of 1.81 (95% CI, 1.74-1.88); 42.4 per 100,000 person-years for skull fracture (95% CI, 36.1-48.7) with an IRR of 2.01 (95% CI, 1.73-2.34, P less than .001), and 50.8 per 100,000 person-years for severe TBI (95% CI, 46.9-54.6) with an IRR of 2.38 (95% CI, 2.20-2.58, P less than .001), compared with individuals with no TBI, the authors wrote.

SOURCE: Madsen T et al. JAMA. 2018 Aug 14;320(6):580-8.

Traumatic brain injury might be associated with an increased risk of suicide, according to results published Aug. 14 in JAMA.

In a retrospective cohort study of 7,418,391 Danish individuals, including 34,529 who died by suicide, patients with medical contact for traumatic brain injury (TBI) had increased suicide risk, compared with the general population (adjusted incidence rate ratio [IRR] = 1.90; 95% confidence interval, 1.83-1.97).

Patients were aged 10 years or older, and follow-up was conducted from Jan. 1, 1980, until date of death, emigration from Denmark, or Dec. 31, 2014, whichever came first. Data were obtained from national registries, including the Danish Civil Registration System, the Database for Integrated Labour Market Research, the National Hospital Register, the Psychiatric Central Research Register, and the Cause of Death Register. Associations between the separate registries were possible because of unique identification numbers assigned to every resident of Denmark, wrote Trine Madsen, PhD, of the Danish Research Institute of Suicide Prevention at the Mental Health Centre Copenhagen, Capital Region of Denmark, and her coauthors.

TBI was recorded in the National Patient Register and was categorized into three types of injury: mild TBI (concussion), skull fracture without documented TBI, and severe TBI (head injury with evidence of structural brain injury). The number of medical contacts for distinct TBI events, accumulated number of days in hospital treatment, age at first TBI, and time since last medical contact for TBI also were assessed.

Data on psychiatric illness and nonfatal self-harm were obtained from the Psychiatric Central Research Register, because of their association with suicide. Data for deaths by suicide were obtained from the Cause of Death Register. Demographic data collected from other registries included sex, age, marital status, cohabitation status, education, and socioeconomic status. IRRs were calculated using adjusted Poisson regression models.

Of 7,418,391 residents of Denmark included in the follow-up period from 1980 to 2014; 567,823 had a TBI diagnosis. Dr. Madsen and her coauthors also found that 423,502 patients (5.7%) were diagnosed with mild TBI, 24,221 (0.3%) with skull fracture, and 120,100 (1.6%) with severe TBI. A total of 34,529 died by suicide.

Of those who died by suicide, 3,536 (10.2%) had a previous TBI diagnosis (2,701 with mild TBI, 174 with skull fracture, and 661 with severe TBI). The absolute rate of suicide in individuals with hospital contact for TBI was 40.6 per 100,000 person-years (95% CI, 39.2-41.9), compared with 19.9 per 100,000 person-years (95% CI, 19.7-20.1) in those with no hospital contact for TBI.

The fully adjusted analysis showed an IRR of 1.90 (95% CI, 1.83-1.97), as well as an increased risk of suicide by TBI severity. The absolute rate for mild TBI was 38.6 per 100,000 person-years (95% CI, 37.1-40.0) with an IRR of 1.81 (95% CI, 1.74-1.88); 42.4 per 100,000 person-years for skull fracture (95% CI, 36.1-48.7) with an IRR of 2.01 (95% CI, 1.73-2.34, P less than .001), and 50.8 per 100,000 person-years for severe TBI (95% CI, 46.9-54.6) with an IRR of 2.38 (95% CI, 2.20-2.58, P less than .001), compared with individuals with no TBI, the authors wrote.

SOURCE: Madsen T et al. JAMA. 2018 Aug 14;320(6):580-8.

Traumatic brain injury might be associated with an increased risk of suicide, according to results published Aug. 14 in JAMA.

In a retrospective cohort study of 7,418,391 Danish individuals, including 34,529 who died by suicide, patients with medical contact for traumatic brain injury (TBI) had increased suicide risk, compared with the general population (adjusted incidence rate ratio [IRR] = 1.90; 95% confidence interval, 1.83-1.97).

Patients were aged 10 years or older, and follow-up was conducted from Jan. 1, 1980, until date of death, emigration from Denmark, or Dec. 31, 2014, whichever came first. Data were obtained from national registries, including the Danish Civil Registration System, the Database for Integrated Labour Market Research, the National Hospital Register, the Psychiatric Central Research Register, and the Cause of Death Register. Associations between the separate registries were possible because of unique identification numbers assigned to every resident of Denmark, wrote Trine Madsen, PhD, of the Danish Research Institute of Suicide Prevention at the Mental Health Centre Copenhagen, Capital Region of Denmark, and her coauthors.

TBI was recorded in the National Patient Register and was categorized into three types of injury: mild TBI (concussion), skull fracture without documented TBI, and severe TBI (head injury with evidence of structural brain injury). The number of medical contacts for distinct TBI events, accumulated number of days in hospital treatment, age at first TBI, and time since last medical contact for TBI also were assessed.

Data on psychiatric illness and nonfatal self-harm were obtained from the Psychiatric Central Research Register, because of their association with suicide. Data for deaths by suicide were obtained from the Cause of Death Register. Demographic data collected from other registries included sex, age, marital status, cohabitation status, education, and socioeconomic status. IRRs were calculated using adjusted Poisson regression models.

Of 7,418,391 residents of Denmark included in the follow-up period from 1980 to 2014; 567,823 had a TBI diagnosis. Dr. Madsen and her coauthors also found that 423,502 patients (5.7%) were diagnosed with mild TBI, 24,221 (0.3%) with skull fracture, and 120,100 (1.6%) with severe TBI. A total of 34,529 died by suicide.

Of those who died by suicide, 3,536 (10.2%) had a previous TBI diagnosis (2,701 with mild TBI, 174 with skull fracture, and 661 with severe TBI). The absolute rate of suicide in individuals with hospital contact for TBI was 40.6 per 100,000 person-years (95% CI, 39.2-41.9), compared with 19.9 per 100,000 person-years (95% CI, 19.7-20.1) in those with no hospital contact for TBI.

The fully adjusted analysis showed an IRR of 1.90 (95% CI, 1.83-1.97), as well as an increased risk of suicide by TBI severity. The absolute rate for mild TBI was 38.6 per 100,000 person-years (95% CI, 37.1-40.0) with an IRR of 1.81 (95% CI, 1.74-1.88); 42.4 per 100,000 person-years for skull fracture (95% CI, 36.1-48.7) with an IRR of 2.01 (95% CI, 1.73-2.34, P less than .001), and 50.8 per 100,000 person-years for severe TBI (95% CI, 46.9-54.6) with an IRR of 2.38 (95% CI, 2.20-2.58, P less than .001), compared with individuals with no TBI, the authors wrote.

SOURCE: Madsen T et al. JAMA. 2018 Aug 14;320(6):580-8.

In the US, 36% of women and 29% of men have experienced rape, physical violence, or stalking by an intimate partner. Research suggests that veterans may be at greater risk for intimate partner violence than civilian counterparts, given the unique stressors posed by military life, such as military deployments that result in family separation, reintegration issues, and combat-related health issues, including PTSD and TBI. According to the VA’s Domestic Violence Task Force, the overall 12-month prevalence of inmate partner violence (IPV) perpetration among active duty service members was 22%, and victimization was 30%. 

To help address this problem, the VA launched the IPV Assistance Program in 2014 and has since established coordinators at more than 115 facilities. The program coordinators use resources from mental health, primary care, women’s health, veterans’ justice outreach, and employee occupational health and assistance programs. The program also offers intervention through VA and community partnerships that address housing, education, and employment needs.

The program takes a holistic approach, focusing on developing a culture of safety, the VA says, with the goal of understanding, recognizing and responding to the effects of all types of trauma, including physical, sexual, and psychological. “We are giving careful attention to this program,” says Acting VA Secretary Peter O’Rourke, “ensuring it is integrated into clinical care and workplace safety.”

In the US, 36% of women and 29% of men have experienced rape, physical violence, or stalking by an intimate partner. Research suggests that veterans may be at greater risk for intimate partner violence than civilian counterparts, given the unique stressors posed by military life, such as military deployments that result in family separation, reintegration issues, and combat-related health issues, including PTSD and TBI. According to the VA’s Domestic Violence Task Force, the overall 12-month prevalence of inmate partner violence (IPV) perpetration among active duty service members was 22%, and victimization was 30%. 

To help address this problem, the VA launched the IPV Assistance Program in 2014 and has since established coordinators at more than 115 facilities. The program coordinators use resources from mental health, primary care, women’s health, veterans’ justice outreach, and employee occupational health and assistance programs. The program also offers intervention through VA and community partnerships that address housing, education, and employment needs.

The program takes a holistic approach, focusing on developing a culture of safety, the VA says, with the goal of understanding, recognizing and responding to the effects of all types of trauma, including physical, sexual, and psychological. “We are giving careful attention to this program,” says Acting VA Secretary Peter O’Rourke, “ensuring it is integrated into clinical care and workplace safety.”

In the US, 36% of women and 29% of men have experienced rape, physical violence, or stalking by an intimate partner. Research suggests that veterans may be at greater risk for intimate partner violence than civilian counterparts, given the unique stressors posed by military life, such as military deployments that result in family separation, reintegration issues, and combat-related health issues, including PTSD and TBI. According to the VA’s Domestic Violence Task Force, the overall 12-month prevalence of inmate partner violence (IPV) perpetration among active duty service members was 22%, and victimization was 30%. 

To help address this problem, the VA launched the IPV Assistance Program in 2014 and has since established coordinators at more than 115 facilities. The program coordinators use resources from mental health, primary care, women’s health, veterans’ justice outreach, and employee occupational health and assistance programs. The program also offers intervention through VA and community partnerships that address housing, education, and employment needs.

The program takes a holistic approach, focusing on developing a culture of safety, the VA says, with the goal of understanding, recognizing and responding to the effects of all types of trauma, including physical, sexual, and psychological. “We are giving careful attention to this program,” says Acting VA Secretary Peter O’Rourke, “ensuring it is integrated into clinical care and workplace safety.”

Many patients with traumatic brain injury (TBI) may not be receiving follow-up care, according to findings from Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI), a long-term NIH-funded study.

Of 831 patients who completed questionnaires 2 weeks and 3 months after sustaining TBI, 44% reported seeing a health care provider within 3 months. Of those, 15% visited a clinic that specialized in head injury. Approximately half saw a general practitioner; close to a third reported seeing ≥ 1 type of doctor.

Among the 279 patients with ≥ 3 symptoms of moderate to severe postconcussion, 41% had not had a follow-up visit at 3 months. Moreover, half of the patients were discharged without TBI educational materials. 

Rates and components of follow-up care varied widely from institution to institution even among patients with the same initial degree of injury.

Many patients with traumatic brain injury (TBI) may not be receiving follow-up care, according to findings from Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI), a long-term NIH-funded study.

Of 831 patients who completed questionnaires 2 weeks and 3 months after sustaining TBI, 44% reported seeing a health care provider within 3 months. Of those, 15% visited a clinic that specialized in head injury. Approximately half saw a general practitioner; close to a third reported seeing ≥ 1 type of doctor.

Among the 279 patients with ≥ 3 symptoms of moderate to severe postconcussion, 41% had not had a follow-up visit at 3 months. Moreover, half of the patients were discharged without TBI educational materials. 

Rates and components of follow-up care varied widely from institution to institution even among patients with the same initial degree of injury.

Many patients with traumatic brain injury (TBI) may not be receiving follow-up care, according to findings from Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI), a long-term NIH-funded study.

Of 831 patients who completed questionnaires 2 weeks and 3 months after sustaining TBI, 44% reported seeing a health care provider within 3 months. Of those, 15% visited a clinic that specialized in head injury. Approximately half saw a general practitioner; close to a third reported seeing ≥ 1 type of doctor.

Among the 279 patients with ≥ 3 symptoms of moderate to severe postconcussion, 41% had not had a follow-up visit at 3 months. Moreover, half of the patients were discharged without TBI educational materials. 

Rates and components of follow-up care varied widely from institution to institution even among patients with the same initial degree of injury.

LOS ANGELES—Plasma levels of neurofilament light indicate repetitive concussive traumatic brain injury (TBI) and axonal injury, according to data presented at the 70th Annual Meeting of the American Academy of Neurology. Differences in this biomarker are detectable for more than a year after the insult. Furthermore, plasma levels of neurofilament light reflect CSF levels of neurofilament light and may identify patients at increased risk of persistent postconcussion syndrome (PCS), according to the researchers.

In a previous study of boxers, Pashtun Shahim, MD, PhD, researcher at the University of Gothenburg in Sweden, and colleagues found that CSF levels of neurofilament light increased more after a bout than did other potential biomarkers such as total tau, phosphorylated tau, and amyloid beta. They also observed that concentrations of serum neurofilament light were higher in boxers with severe head impact, compared with those with mild head impact. In a study of hockey players, Dr. Shahim and colleagues found that neurofilament light measured in the acute setting could distinguish those who would have a prolonged return to play from those who would have a quick return to play.

A Study of Professional Athletes

In their latest study, Dr. Shahim and colleagues sought to determine whether professional athletes with PCS resulting from repetitive concussive TBI have elevated CSF and plasma neurofilament light and tau, compared with controls. They also investigated whether elevated concentrations of these biomarkers are associated with persistent PCS.

Between September 2013 and September 2017, the investigators enrolled 31 athletes (ie, professional players of hockey and soccer) with PCS resulting from repetitive concussive TBI, 48 athletes with concussion but without PCS, and 30 control athletes into their study. Participants underwent CSF and plasma biomarker assessments, responded to the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), and underwent structural brain MRI. The population’s median time since the last concussion was 1.5 years. The three groups were matched on sport.

Biomarker Indicated Duration of PCS

Dr. Shahim and colleagues found “a tight correlation between plasma concentrations of neurofilament [light] and CSF neurofilament [light], while there was no correlation between plasma tau and CSF tau.”

Plasma neurofilament light concentrations were significantly increased in participants with concussion and those with PCS, compared with controls. The concentration of plasma neurofilament light was higher in patients with concussion but without PCS, compared with the PCS group. This finding was “expected, as we are comparing acute cases of concussion versus chronic cases,” said Dr. Shahim.

When they examined only participants with PCS, athletes who had had PCS for more than one year had higher concentrations of neurofilament light, compared with athletes who had had PCS for less than one year. The latter returned to play, while the former resigned, said Dr. Shahim. In addition, plasma neurofilament light concentration correlated with RPQ scores and lifetime number of concussions.

Levels of tau were lower among participants with PCS than among control athletes, and the researchers found no correlation between tau level and duration of PCS. Levels of tau also had no association with RPQ scores.

Dr. Shahim and colleagues next examined whether these biomarkers had prognostic value. They found that CSF neurofilament concentrations could distinguish between participants who had had PCS for less than a year and those who had had PCS for more than a year (area under the curve [AUC], 0.86). Plasma neurofilament light distinguished between these groups with an AUC of 0.85. Neither CSF tau nor plasma tau reliably indicated duration of PCS, however. In addition, the investigators found no correlation between CSF and plasma tau concentrations from the same individual. This finding casts doubt on the hypothesis that tau concentrations reflect axonal injury, said Dr. Shahim.

—Erik Greb

Suggested Reading

Shahim P, Tegner Y, Marklund N, et al. Neurofilament light and tau as blood biomarkers for sports-related concussion. Neurology. 2018;90(20):e1780-e1788.

Shahim P, Zetterberg H, Tegner Y, Blennow K. Serum neurofilament light as a biomarker for mild traumatic brain injury in contact sports. Neurology. 2017;88(19):1788-1794.

LOS ANGELES—Plasma levels of neurofilament light indicate repetitive concussive traumatic brain injury (TBI) and axonal injury, according to data presented at the 70th Annual Meeting of the American Academy of Neurology. Differences in this biomarker are detectable for more than a year after the insult. Furthermore, plasma levels of neurofilament light reflect CSF levels of neurofilament light and may identify patients at increased risk of persistent postconcussion syndrome (PCS), according to the researchers.

In a previous study of boxers, Pashtun Shahim, MD, PhD, researcher at the University of Gothenburg in Sweden, and colleagues found that CSF levels of neurofilament light increased more after a bout than did other potential biomarkers such as total tau, phosphorylated tau, and amyloid beta. They also observed that concentrations of serum neurofilament light were higher in boxers with severe head impact, compared with those with mild head impact. In a study of hockey players, Dr. Shahim and colleagues found that neurofilament light measured in the acute setting could distinguish those who would have a prolonged return to play from those who would have a quick return to play.

A Study of Professional Athletes

In their latest study, Dr. Shahim and colleagues sought to determine whether professional athletes with PCS resulting from repetitive concussive TBI have elevated CSF and plasma neurofilament light and tau, compared with controls. They also investigated whether elevated concentrations of these biomarkers are associated with persistent PCS.

Between September 2013 and September 2017, the investigators enrolled 31 athletes (ie, professional players of hockey and soccer) with PCS resulting from repetitive concussive TBI, 48 athletes with concussion but without PCS, and 30 control athletes into their study. Participants underwent CSF and plasma biomarker assessments, responded to the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), and underwent structural brain MRI. The population’s median time since the last concussion was 1.5 years. The three groups were matched on sport.

Biomarker Indicated Duration of PCS

Dr. Shahim and colleagues found “a tight correlation between plasma concentrations of neurofilament [light] and CSF neurofilament [light], while there was no correlation between plasma tau and CSF tau.”

Plasma neurofilament light concentrations were significantly increased in participants with concussion and those with PCS, compared with controls. The concentration of plasma neurofilament light was higher in patients with concussion but without PCS, compared with the PCS group. This finding was “expected, as we are comparing acute cases of concussion versus chronic cases,” said Dr. Shahim.

When they examined only participants with PCS, athletes who had had PCS for more than one year had higher concentrations of neurofilament light, compared with athletes who had had PCS for less than one year. The latter returned to play, while the former resigned, said Dr. Shahim. In addition, plasma neurofilament light concentration correlated with RPQ scores and lifetime number of concussions.

Levels of tau were lower among participants with PCS than among control athletes, and the researchers found no correlation between tau level and duration of PCS. Levels of tau also had no association with RPQ scores.

Dr. Shahim and colleagues next examined whether these biomarkers had prognostic value. They found that CSF neurofilament concentrations could distinguish between participants who had had PCS for less than a year and those who had had PCS for more than a year (area under the curve [AUC], 0.86). Plasma neurofilament light distinguished between these groups with an AUC of 0.85. Neither CSF tau nor plasma tau reliably indicated duration of PCS, however. In addition, the investigators found no correlation between CSF and plasma tau concentrations from the same individual. This finding casts doubt on the hypothesis that tau concentrations reflect axonal injury, said Dr. Shahim.

—Erik Greb

Suggested Reading

Shahim P, Tegner Y, Marklund N, et al. Neurofilament light and tau as blood biomarkers for sports-related concussion. Neurology. 2018;90(20):e1780-e1788.

Shahim P, Zetterberg H, Tegner Y, Blennow K. Serum neurofilament light as a biomarker for mild traumatic brain injury in contact sports. Neurology. 2017;88(19):1788-1794.

LOS ANGELES—Plasma levels of neurofilament light indicate repetitive concussive traumatic brain injury (TBI) and axonal injury, according to data presented at the 70th Annual Meeting of the American Academy of Neurology. Differences in this biomarker are detectable for more than a year after the insult. Furthermore, plasma levels of neurofilament light reflect CSF levels of neurofilament light and may identify patients at increased risk of persistent postconcussion syndrome (PCS), according to the researchers.

In a previous study of boxers, Pashtun Shahim, MD, PhD, researcher at the University of Gothenburg in Sweden, and colleagues found that CSF levels of neurofilament light increased more after a bout than did other potential biomarkers such as total tau, phosphorylated tau, and amyloid beta. They also observed that concentrations of serum neurofilament light were higher in boxers with severe head impact, compared with those with mild head impact. In a study of hockey players, Dr. Shahim and colleagues found that neurofilament light measured in the acute setting could distinguish those who would have a prolonged return to play from those who would have a quick return to play.

A Study of Professional Athletes

In their latest study, Dr. Shahim and colleagues sought to determine whether professional athletes with PCS resulting from repetitive concussive TBI have elevated CSF and plasma neurofilament light and tau, compared with controls. They also investigated whether elevated concentrations of these biomarkers are associated with persistent PCS.

Between September 2013 and September 2017, the investigators enrolled 31 athletes (ie, professional players of hockey and soccer) with PCS resulting from repetitive concussive TBI, 48 athletes with concussion but without PCS, and 30 control athletes into their study. Participants underwent CSF and plasma biomarker assessments, responded to the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), and underwent structural brain MRI. The population’s median time since the last concussion was 1.5 years. The three groups were matched on sport.

Biomarker Indicated Duration of PCS

Dr. Shahim and colleagues found “a tight correlation between plasma concentrations of neurofilament [light] and CSF neurofilament [light], while there was no correlation between plasma tau and CSF tau.”

Plasma neurofilament light concentrations were significantly increased in participants with concussion and those with PCS, compared with controls. The concentration of plasma neurofilament light was higher in patients with concussion but without PCS, compared with the PCS group. This finding was “expected, as we are comparing acute cases of concussion versus chronic cases,” said Dr. Shahim.

When they examined only participants with PCS, athletes who had had PCS for more than one year had higher concentrations of neurofilament light, compared with athletes who had had PCS for less than one year. The latter returned to play, while the former resigned, said Dr. Shahim. In addition, plasma neurofilament light concentration correlated with RPQ scores and lifetime number of concussions.

Levels of tau were lower among participants with PCS than among control athletes, and the researchers found no correlation between tau level and duration of PCS. Levels of tau also had no association with RPQ scores.

Dr. Shahim and colleagues next examined whether these biomarkers had prognostic value. They found that CSF neurofilament concentrations could distinguish between participants who had had PCS for less than a year and those who had had PCS for more than a year (area under the curve [AUC], 0.86). Plasma neurofilament light distinguished between these groups with an AUC of 0.85. Neither CSF tau nor plasma tau reliably indicated duration of PCS, however. In addition, the investigators found no correlation between CSF and plasma tau concentrations from the same individual. This finding casts doubt on the hypothesis that tau concentrations reflect axonal injury, said Dr. Shahim.

—Erik Greb

Suggested Reading

Shahim P, Tegner Y, Marklund N, et al. Neurofilament light and tau as blood biomarkers for sports-related concussion. Neurology. 2018;90(20):e1780-e1788.

Shahim P, Zetterberg H, Tegner Y, Blennow K. Serum neurofilament light as a biomarker for mild traumatic brain injury in contact sports. Neurology. 2017;88(19):1788-1794.

Younger age of exposure to tackle football is not associated with chronic traumatic encephalopathy (CTE) pathologic severity, Alzheimer’s disease pathology, or Lewy body pathology, according to data published online ahead of print April 30 in Annals of Neurology. Younger age of exposure does appear to predict earlier neurobehavioral symptom onset, however, the authors said.

“These findings suggest that exposure to repetitive head impacts from tackle football as a youth may reduce resiliency to diseases, including, but not limited to, CTE, that affect the brain in later life,” said Michael L. Alosco, PhD, Assistant Professor of Neurology at the the Boston University Alzheimer’s Disease and CTE Center. “This study adds to growing research suggesting that incurring repeated head impacts through tackle football in earlier life can lead to both short-term and long-term effects on the brain.”

Repetitive Head Impacts and Neurodevelopment

Previous research has linked younger age of first exposure to tackle football with smaller thalamic volume in former National Football League players. A recent study of 214 former and amateur football players found that age of first exposure to tackle football—before age 12, in particular—predicted increased odds of self-reported neuropsychiatric and executive impairment.

“Youth exposure to repetitive head impacts may disrupt neurodevelopment to lower the threshold for later clinical dysfunction,” said the researchers.

To examine the effect of age of first exposure to tackle football on CTE pathologic severity and age of neurobehavioral symptom onset in tackle football players with neuropathologically confirmed CTE, Dr. Alosco and colleagues analyzed a sample of 246 amateur and professional tackle football players whose brains had been donated to the Veteran’s Affairs–Boston University–Concussion Legacy Foundation Brain Bank. The researchers interviewed informants to ascertain players’ age of first exposure and age of onset of cognitive, behavioral, or mood symptoms. A total of 211 football players were diagnosed with CTE; 35 did not have CTE. Of the 211 participants with CTE, 126 had CTE only, and the other participants had comorbid neurodegenerative diseases.

Onset of Cognitive, Behavioral, and Mood Symptoms

Of the 211 participants with CTE, 183 developed cognitive and behavioral or mood symptoms prior to death, eight had only cognitive symptoms, 12 had only behavioral or mood symptoms, and seven did not endorse any symptoms examined in the study. Clinical data for one participant were not available.

Among tackle football players with CTE, every one year younger that they began to play tackle football predicted earlier onset of cognitive symptoms by 2.44 years and of behavioral or mood symptoms by 2.50 years. Exposure before age 12 predicted earlier cognitive and behavioral or mood symptom onset by 13.39 years and 13.28 years, respectively.

Secondary subset analyses indicated that younger age of exposure to tackle football was associated with earlier onset of functional impairment in participants who were determined to have had dementia. Researchers observed nearly identical effects in participants with CTE only.

Study limitations include the lack of an appropriate control or comparison group, the researchers noted. In addition, the results may not be generalizable to a broader tackle football population.

“Given the growing public health concerns for participation in tackle football, prospective studies of former tackle football players that include objective clinical assessments are needed to better understand the relationship between youth tackle football exposure and long-term neurobehavioral outcomes,” said the researchers.

“More research on this topic is needed before any clinical recommendations, as well as recommendations on policy or rule changes, can be made,” said Dr. Alosco.

“Boston University and sites across the country are currently conducting longitudinal studies on former football players, which will allow us to begin to study cognition and behavior and mood functioning over time.”

—Erica Tricarico

Suggested Reading

Alosco ML, Mez J, Tripodis Y, et al. Age of first exposure to tackle football and chronic traumatic encephalopathy. Ann Neurol. 2018 Apr 30 [Epub ahead of print].

Younger age of exposure to tackle football is not associated with chronic traumatic encephalopathy (CTE) pathologic severity, Alzheimer’s disease pathology, or Lewy body pathology, according to data published online ahead of print April 30 in Annals of Neurology. Younger age of exposure does appear to predict earlier neurobehavioral symptom onset, however, the authors said.

“These findings suggest that exposure to repetitive head impacts from tackle football as a youth may reduce resiliency to diseases, including, but not limited to, CTE, that affect the brain in later life,” said Michael L. Alosco, PhD, Assistant Professor of Neurology at the the Boston University Alzheimer’s Disease and CTE Center. “This study adds to growing research suggesting that incurring repeated head impacts through tackle football in earlier life can lead to both short-term and long-term effects on the brain.”

Repetitive Head Impacts and Neurodevelopment

Previous research has linked younger age of first exposure to tackle football with smaller thalamic volume in former National Football League players. A recent study of 214 former and amateur football players found that age of first exposure to tackle football—before age 12, in particular—predicted increased odds of self-reported neuropsychiatric and executive impairment.

“Youth exposure to repetitive head impacts may disrupt neurodevelopment to lower the threshold for later clinical dysfunction,” said the researchers.

To examine the effect of age of first exposure to tackle football on CTE pathologic severity and age of neurobehavioral symptom onset in tackle football players with neuropathologically confirmed CTE, Dr. Alosco and colleagues analyzed a sample of 246 amateur and professional tackle football players whose brains had been donated to the Veteran’s Affairs–Boston University–Concussion Legacy Foundation Brain Bank. The researchers interviewed informants to ascertain players’ age of first exposure and age of onset of cognitive, behavioral, or mood symptoms. A total of 211 football players were diagnosed with CTE; 35 did not have CTE. Of the 211 participants with CTE, 126 had CTE only, and the other participants had comorbid neurodegenerative diseases.

Onset of Cognitive, Behavioral, and Mood Symptoms

Of the 211 participants with CTE, 183 developed cognitive and behavioral or mood symptoms prior to death, eight had only cognitive symptoms, 12 had only behavioral or mood symptoms, and seven did not endorse any symptoms examined in the study. Clinical data for one participant were not available.

Among tackle football players with CTE, every one year younger that they began to play tackle football predicted earlier onset of cognitive symptoms by 2.44 years and of behavioral or mood symptoms by 2.50 years. Exposure before age 12 predicted earlier cognitive and behavioral or mood symptom onset by 13.39 years and 13.28 years, respectively.

Secondary subset analyses indicated that younger age of exposure to tackle football was associated with earlier onset of functional impairment in participants who were determined to have had dementia. Researchers observed nearly identical effects in participants with CTE only.

Study limitations include the lack of an appropriate control or comparison group, the researchers noted. In addition, the results may not be generalizable to a broader tackle football population.

“Given the growing public health concerns for participation in tackle football, prospective studies of former tackle football players that include objective clinical assessments are needed to better understand the relationship between youth tackle football exposure and long-term neurobehavioral outcomes,” said the researchers.

“More research on this topic is needed before any clinical recommendations, as well as recommendations on policy or rule changes, can be made,” said Dr. Alosco.

“Boston University and sites across the country are currently conducting longitudinal studies on former football players, which will allow us to begin to study cognition and behavior and mood functioning over time.”

—Erica Tricarico

Suggested Reading

Alosco ML, Mez J, Tripodis Y, et al. Age of first exposure to tackle football and chronic traumatic encephalopathy. Ann Neurol. 2018 Apr 30 [Epub ahead of print].

Younger age of exposure to tackle football is not associated with chronic traumatic encephalopathy (CTE) pathologic severity, Alzheimer’s disease pathology, or Lewy body pathology, according to data published online ahead of print April 30 in Annals of Neurology. Younger age of exposure does appear to predict earlier neurobehavioral symptom onset, however, the authors said.

“These findings suggest that exposure to repetitive head impacts from tackle football as a youth may reduce resiliency to diseases, including, but not limited to, CTE, that affect the brain in later life,” said Michael L. Alosco, PhD, Assistant Professor of Neurology at the the Boston University Alzheimer’s Disease and CTE Center. “This study adds to growing research suggesting that incurring repeated head impacts through tackle football in earlier life can lead to both short-term and long-term effects on the brain.”

Repetitive Head Impacts and Neurodevelopment

Previous research has linked younger age of first exposure to tackle football with smaller thalamic volume in former National Football League players. A recent study of 214 former and amateur football players found that age of first exposure to tackle football—before age 12, in particular—predicted increased odds of self-reported neuropsychiatric and executive impairment.

“Youth exposure to repetitive head impacts may disrupt neurodevelopment to lower the threshold for later clinical dysfunction,” said the researchers.

To examine the effect of age of first exposure to tackle football on CTE pathologic severity and age of neurobehavioral symptom onset in tackle football players with neuropathologically confirmed CTE, Dr. Alosco and colleagues analyzed a sample of 246 amateur and professional tackle football players whose brains had been donated to the Veteran’s Affairs–Boston University–Concussion Legacy Foundation Brain Bank. The researchers interviewed informants to ascertain players’ age of first exposure and age of onset of cognitive, behavioral, or mood symptoms. A total of 211 football players were diagnosed with CTE; 35 did not have CTE. Of the 211 participants with CTE, 126 had CTE only, and the other participants had comorbid neurodegenerative diseases.

Onset of Cognitive, Behavioral, and Mood Symptoms

Of the 211 participants with CTE, 183 developed cognitive and behavioral or mood symptoms prior to death, eight had only cognitive symptoms, 12 had only behavioral or mood symptoms, and seven did not endorse any symptoms examined in the study. Clinical data for one participant were not available.

Among tackle football players with CTE, every one year younger that they began to play tackle football predicted earlier onset of cognitive symptoms by 2.44 years and of behavioral or mood symptoms by 2.50 years. Exposure before age 12 predicted earlier cognitive and behavioral or mood symptom onset by 13.39 years and 13.28 years, respectively.

Secondary subset analyses indicated that younger age of exposure to tackle football was associated with earlier onset of functional impairment in participants who were determined to have had dementia. Researchers observed nearly identical effects in participants with CTE only.

Study limitations include the lack of an appropriate control or comparison group, the researchers noted. In addition, the results may not be generalizable to a broader tackle football population.

“Given the growing public health concerns for participation in tackle football, prospective studies of former tackle football players that include objective clinical assessments are needed to better understand the relationship between youth tackle football exposure and long-term neurobehavioral outcomes,” said the researchers.

“More research on this topic is needed before any clinical recommendations, as well as recommendations on policy or rule changes, can be made,” said Dr. Alosco.

“Boston University and sites across the country are currently conducting longitudinal studies on former football players, which will allow us to begin to study cognition and behavior and mood functioning over time.”

—Erica Tricarico

Suggested Reading

Alosco ML, Mez J, Tripodis Y, et al. Age of first exposure to tackle football and chronic traumatic encephalopathy. Ann Neurol. 2018 Apr 30 [Epub ahead of print].

Among military veterans, mild traumatic brain injury (TBI) is associated with a 56% increased risk of developing Parkinson’s disease over 12 years of follow-up, according to data published online ahead of print April 18 in Neurology. Prior TBI also is associated with a diagnosis of Parkinson’s disease two years earlier than among controls.

“Our findings highlight the critical importance of unraveling mechanisms subserving the association between TBI and Parkinson’s disease to inform treatment and prevention of post-TBI Parkinson’s disease,” said Raquel C. Gardner, MD, Assistant Professor of Neurology at the University of California, San Francisco.

A Longitudinal Cohort Study

Every year, mild TBI affects an estimated 42 million people worldwide. It is especially common among athletes and military personnel and is a growing epidemic among the elderly. In 2008, the Institute of Medicine found sufficient evidence to suggest an association between moderate to severe TBI and a clinical diagnosis of Parkinson’s disease, but limited evidence for an association between mild TBI with loss of consciousness and a clinical diagnosis of Parkinson’s disease. One small case–control study assessed the risk of Parkinson’s disease following mild TBI among military veterans, but the results were inconclusive, said the authors.

Dr. Gardner and colleagues conducted a longitudinal cohort study to evaluate the risk of Parkinson’s disease following TBI, including mild TBI, among patients in the Veterans Health Administration (VHA). They analyzed data from three nationwide VHA health care system databases and identified patients with a diagnosis of TBI from October 2002 to September 2014. Participants were age 18 or older without Parkinson’s disease or dementia at baseline and were age-matched 1:1 to a random sample of patients without TBI.

Researchers defined moderate to severe TBI as a loss of consciousness for more than 30 minutes, alteration of consciousness for more than 24 hours, or amnesia for more than 24 hours. They defined mild TBI as loss of consciousness for zero to 30 minutes, alteration of consciousness for a moment to 24 hours, or amnesia for zero to 24 hours.

TBI exposure and severity were determined via detailed clinical assessments or ICD-9 codes using Department of Defense and Defense and Veterans Brain Injury Center criteria. Baseline comorbidities and incident Parkinson’s disease at more than one year post TBI were identified using ICD-9 codes. In addition, investigators used Cox proportional hazard models adjusted for demographics and medical and psychiatric comorbidities to assess risk of Parkinson’s disease after TBI.

Prior TBI Was Associated With Minority Status

A total of 325,870 patients were included in the study with an average age of 47.9 and an average follow-up of 4.6 years. In all, 1,462 patients were diagnosed with Parkinson’s disease during follow-up. After adjusting for age, sex, race, education, and other health conditions, the researchers found that patients with any severity of TBI had a 71% increased risk of Parkinson’s disease; participants with moderate to severe TBI had an 83% increased risk.

Overall, patients with prior TBI were diagnosed with Parkinson’s disease at a significantly younger age, had significantly higher prevalence of non-Hispanic black and Hispanic race or ethnicity, and had significantly higher prevalence of all medical and psychiatric comorbidities, compared with those without prior TBI.

“Given the growing evidence for several potentially modifiable risk factors for Parkinson’s disease, an important area for future research will be to determine whether improved management of specific highly prevalent comorbidities among TBI-exposed veterans may reduce risk of subsequent Parkinson’s disease,” said the researchers.

Strengths of this study include the use of physicians’ diagnosis of TBI and Parkinson’s disease, a longitudinal cohort design, and a large sample size. One of the study’s limitations was the use of ICD-9 codes for the diagnosis of TBI and Parkinson’s disease, which may have overlooked some cases, such as TBI with polytrauma or mild TBI sustained in combat, said the authors. NR

—Erica Tricarico

Suggested Reading

Gardner RC, Byers AL, Barnes DE, et al. Mild TBI and risk of Parkinson disease: a chronic effects of neurotrauma consortium study. Neurology. 2018 Apr 18 [Epub ahead of print].

Among military veterans, mild traumatic brain injury (TBI) is associated with a 56% increased risk of developing Parkinson’s disease over 12 years of follow-up, according to data published online ahead of print April 18 in Neurology. Prior TBI also is associated with a diagnosis of Parkinson’s disease two years earlier than among controls.

“Our findings highlight the critical importance of unraveling mechanisms subserving the association between TBI and Parkinson’s disease to inform treatment and prevention of post-TBI Parkinson’s disease,” said Raquel C. Gardner, MD, Assistant Professor of Neurology at the University of California, San Francisco.

A Longitudinal Cohort Study

Every year, mild TBI affects an estimated 42 million people worldwide. It is especially common among athletes and military personnel and is a growing epidemic among the elderly. In 2008, the Institute of Medicine found sufficient evidence to suggest an association between moderate to severe TBI and a clinical diagnosis of Parkinson’s disease, but limited evidence for an association between mild TBI with loss of consciousness and a clinical diagnosis of Parkinson’s disease. One small case–control study assessed the risk of Parkinson’s disease following mild TBI among military veterans, but the results were inconclusive, said the authors.

Dr. Gardner and colleagues conducted a longitudinal cohort study to evaluate the risk of Parkinson’s disease following TBI, including mild TBI, among patients in the Veterans Health Administration (VHA). They analyzed data from three nationwide VHA health care system databases and identified patients with a diagnosis of TBI from October 2002 to September 2014. Participants were age 18 or older without Parkinson’s disease or dementia at baseline and were age-matched 1:1 to a random sample of patients without TBI.

Researchers defined moderate to severe TBI as a loss of consciousness for more than 30 minutes, alteration of consciousness for more than 24 hours, or amnesia for more than 24 hours. They defined mild TBI as loss of consciousness for zero to 30 minutes, alteration of consciousness for a moment to 24 hours, or amnesia for zero to 24 hours.

TBI exposure and severity were determined via detailed clinical assessments or ICD-9 codes using Department of Defense and Defense and Veterans Brain Injury Center criteria. Baseline comorbidities and incident Parkinson’s disease at more than one year post TBI were identified using ICD-9 codes. In addition, investigators used Cox proportional hazard models adjusted for demographics and medical and psychiatric comorbidities to assess risk of Parkinson’s disease after TBI.

Prior TBI Was Associated With Minority Status

A total of 325,870 patients were included in the study with an average age of 47.9 and an average follow-up of 4.6 years. In all, 1,462 patients were diagnosed with Parkinson’s disease during follow-up. After adjusting for age, sex, race, education, and other health conditions, the researchers found that patients with any severity of TBI had a 71% increased risk of Parkinson’s disease; participants with moderate to severe TBI had an 83% increased risk.

Overall, patients with prior TBI were diagnosed with Parkinson’s disease at a significantly younger age, had significantly higher prevalence of non-Hispanic black and Hispanic race or ethnicity, and had significantly higher prevalence of all medical and psychiatric comorbidities, compared with those without prior TBI.

“Given the growing evidence for several potentially modifiable risk factors for Parkinson’s disease, an important area for future research will be to determine whether improved management of specific highly prevalent comorbidities among TBI-exposed veterans may reduce risk of subsequent Parkinson’s disease,” said the researchers.

Strengths of this study include the use of physicians’ diagnosis of TBI and Parkinson’s disease, a longitudinal cohort design, and a large sample size. One of the study’s limitations was the use of ICD-9 codes for the diagnosis of TBI and Parkinson’s disease, which may have overlooked some cases, such as TBI with polytrauma or mild TBI sustained in combat, said the authors. NR

—Erica Tricarico

Suggested Reading

Gardner RC, Byers AL, Barnes DE, et al. Mild TBI and risk of Parkinson disease: a chronic effects of neurotrauma consortium study. Neurology. 2018 Apr 18 [Epub ahead of print].

Among military veterans, mild traumatic brain injury (TBI) is associated with a 56% increased risk of developing Parkinson’s disease over 12 years of follow-up, according to data published online ahead of print April 18 in Neurology. Prior TBI also is associated with a diagnosis of Parkinson’s disease two years earlier than among controls.

“Our findings highlight the critical importance of unraveling mechanisms subserving the association between TBI and Parkinson’s disease to inform treatment and prevention of post-TBI Parkinson’s disease,” said Raquel C. Gardner, MD, Assistant Professor of Neurology at the University of California, San Francisco.

A Longitudinal Cohort Study

Every year, mild TBI affects an estimated 42 million people worldwide. It is especially common among athletes and military personnel and is a growing epidemic among the elderly. In 2008, the Institute of Medicine found sufficient evidence to suggest an association between moderate to severe TBI and a clinical diagnosis of Parkinson’s disease, but limited evidence for an association between mild TBI with loss of consciousness and a clinical diagnosis of Parkinson’s disease. One small case–control study assessed the risk of Parkinson’s disease following mild TBI among military veterans, but the results were inconclusive, said the authors.

Dr. Gardner and colleagues conducted a longitudinal cohort study to evaluate the risk of Parkinson’s disease following TBI, including mild TBI, among patients in the Veterans Health Administration (VHA). They analyzed data from three nationwide VHA health care system databases and identified patients with a diagnosis of TBI from October 2002 to September 2014. Participants were age 18 or older without Parkinson’s disease or dementia at baseline and were age-matched 1:1 to a random sample of patients without TBI.

Researchers defined moderate to severe TBI as a loss of consciousness for more than 30 minutes, alteration of consciousness for more than 24 hours, or amnesia for more than 24 hours. They defined mild TBI as loss of consciousness for zero to 30 minutes, alteration of consciousness for a moment to 24 hours, or amnesia for zero to 24 hours.

TBI exposure and severity were determined via detailed clinical assessments or ICD-9 codes using Department of Defense and Defense and Veterans Brain Injury Center criteria. Baseline comorbidities and incident Parkinson’s disease at more than one year post TBI were identified using ICD-9 codes. In addition, investigators used Cox proportional hazard models adjusted for demographics and medical and psychiatric comorbidities to assess risk of Parkinson’s disease after TBI.

Prior TBI Was Associated With Minority Status

A total of 325,870 patients were included in the study with an average age of 47.9 and an average follow-up of 4.6 years. In all, 1,462 patients were diagnosed with Parkinson’s disease during follow-up. After adjusting for age, sex, race, education, and other health conditions, the researchers found that patients with any severity of TBI had a 71% increased risk of Parkinson’s disease; participants with moderate to severe TBI had an 83% increased risk.

Overall, patients with prior TBI were diagnosed with Parkinson’s disease at a significantly younger age, had significantly higher prevalence of non-Hispanic black and Hispanic race or ethnicity, and had significantly higher prevalence of all medical and psychiatric comorbidities, compared with those without prior TBI.

“Given the growing evidence for several potentially modifiable risk factors for Parkinson’s disease, an important area for future research will be to determine whether improved management of specific highly prevalent comorbidities among TBI-exposed veterans may reduce risk of subsequent Parkinson’s disease,” said the researchers.

Strengths of this study include the use of physicians’ diagnosis of TBI and Parkinson’s disease, a longitudinal cohort design, and a large sample size. One of the study’s limitations was the use of ICD-9 codes for the diagnosis of TBI and Parkinson’s disease, which may have overlooked some cases, such as TBI with polytrauma or mild TBI sustained in combat, said the authors. NR

—Erica Tricarico

Suggested Reading

Gardner RC, Byers AL, Barnes DE, et al. Mild TBI and risk of Parkinson disease: a chronic effects of neurotrauma consortium study. Neurology. 2018 Apr 18 [Epub ahead of print].