Traumatic Brain Injury in Women · Katherine M. Helmick, M.S., CRNP, ANP-BC, CNRN Deputy Director, Defense and Veterans Brain Injury Center (DVBIC)/TBI CoE. J9- Research and Development/Defense

Traumatic Brain Injury in WomenKatherine M. Helmick, M.S., CRNP, ANP-BC, CNRN

Deputy Director, Defense and Veterans Brain Injury Center (DVBIC)/TBI CoEJ9- Research and Development/Defense Health Agency

National VA/DoD Women's Mental Health Mini-Residency: Building Clinical Expertise to Meet Women's Unique Treatment Needs

Crystal City, Virginia | August 28-30, 2018

“Medically Ready Force…Ready Medical Force” 1

Disclosures

The views expressed in this presentation are those of the speaker and do not necessarily reflect the official policy or position of the Department of Defense or the U.S. government.

This continuing education activity is managed and accredited by the Department of Veterans Affairs, Employee Education System (VA-EES).

Katherine M. Helmick and TBI Center of Excellence staff have no financial interest to disclose. Commercial support was not received for this activity.


Learning Objectives

At the conclusion of this presentation, participants will be able to: Interpret and compare various DVBIC clinical resources, including

clinical recommendations (CRs), clinical practice guidelines (CPGs), and other clinical support tools (CSTs) and illustrate how these resources can be implemented in a variety of clinical settings.

Describe various policies and programs that support traumatic brain injury (TBI) care in the military environment.

Describe two differences in TBI rates and post concussive symptom reporting between men and women.

Describe the research gaps related to TBI in women.


Defense and Veterans Brain Injury Center (DVBIC)

MissionAs the MHS TBI Pathway of Care manager, DVBIC promotes state-of-the-science care from point of injury to reintegration for service members, veterans, and their families to prevent and mitigate consequences of mild to severe traumatic brain injury (TBI).Mission DriversFrom 1991 until the present, DVBIC has received multiple congressional and Health Affairs mandates:∎ Congress

1991: Sec 255: Created DVBIC as the Defense and Veterans Head Injury Program 2007: Sec 721: Authorized DVBIC’s 15-year longitudinal study on long term

effects of TBI∎ DoD Health Affairs

2014: ASD/HA - Established DVBIC’s role as TBI Pathway of Care manager 2016: Lead for ASD/HA requested TBI consensus statement initiative


DVBIC Core Functions

DVBIC Partners:

ISC/NICoE USU/CNRM MRMC Federal / academia Industry TBI community of interest


DVBIC Org Chart


DVBIC Creates Conditions to Translate State-of-the-Science Knowledge

DVBIC employs an integrated enterprise-approach (TBI Pathway of Care) to rapidly translate scientific knowledge into products, actionable guidance and policy to improve the health outcomes of our service members, veterans, and their families.

Knowledge

Translation and Implementation

Clinical Care

• Needs & gaps identification• Evidence review & analysis• Focused military research• Health outcomes &

surveillance• Engagement with services

and TBI partners

• Develop TBI clinical recommendations & products

• Manage TBI Pathway of Care • Guide TBI policy• Provider education• Outreach & product

dissemination throughout 22 network sites


Traumatic Brain Injury (TBI)

(Memorandum: TBI Updated Definition and Reporting, April 06, 2015)∎ A traumatically induced structural injury or physiological

disruption of brain function as a result of an external force, that is indicated by new onset or worsening of at least one of the following clinical signs, immediately following the event:Any period of loss of or decrease of consciousness, observed or

self-reported (LOC)Any loss of memory for events immediately before or after the

injury (PTA)Any alteration in mental status (confusion, slowed thinking,

disorientation) (AOC)


Continuum of TBI Care

Prevention Screening Diagnosis Treatment Rehab/Recovery Reintegration

Surveillance

Research


What Does Concussion (mTBI) Look Like?

∎ https://www.youtube.com/watch?v=q3pyMK6srd8&t=3s

∎Acute Concussion∎ Chronic persistent post concussion symptoms


https://www.youtube.com/watch?v=q3pyMK6srd8&t=3s

All DoD TBI Incidence

About 87% of all TBIs are

diagnosed in the Non-deployed setting

82.3% of all TBIs are

mild/ concussion

Annual Department of Defense TBI Diagnoses (All Severities) 2000 – 2017

Year Number2000 10,9592001 11,6192002 12,4072003 12,8152004 14,4682005 15,5282006 17,0222007 23,2212008 28,4792009 28,8952010 29,3672011 32,8382012 30,6502013 27,4522014 25,0682015 22,6942016 18,3302017 17,707Total 379,519


DVBIC Sites Strategically Located to Engage Providers and Patients (FY17Q1-Q3)


DoD Policy (DODI 6490.11)

∎ Requires screening and mandatory 24 hours rest for all services members exposed to potentially concussive events in a deployed setting Army (and soon other services) expanded the policy to include the

non-deployed setting. Army Execution Order 165-13 signed June 2013. Applies whether or not the event happens on duty. Requires evaluation by medical provider with 12 hours. One-time (concussion in garrison), annual and pre deployment

(TBI) training required.

DESIRED END STATE: the mitigation of the effects of potential concussive events on both service member

health, readiness and ongoing operations


Mandatory Events Requiring Evaluation

∎ Exposure to the following events mandates prompt command and medical concussion evaluation, event reporting and a 24-hour rest period:Any service member in a vehicle associated with a blast

event, collision or rollover.All within 50 meters of a blast (inside or outside).Anyone who sustains a direct blow to the head.Command directed, including but not limited to repeated

exposures to blasts.


Concussion/mTBI Screening and Assessment

Military Acute Concussion Evaluation (MACE)

Concussion Management Algorithms


Diagnosis: Emerging Science on Objective Markers of Concussion

Examples for possible objective markers of concussion (not limited to):∎ Biomarkers – several highly sensitive but low specificity∎ - S100B, neuronal specific enolase (NSE), ubiquitin C-hydrolase L-1

(UCH-L1), glial fibrillary astrocytic protein (GFAP), tau∎ Imaging – Diffusion Tensor Imaging (DTI) (Blast-related TBI using DTI)∎ Electrophysiologic parameters – qEEG, event related potentials,

heart rate (Hand Held Real time multichannel EEG : Brainscope One, Infrascan)

∎ Vestibular and Oculomotor Testing: VOMS (vestibular oculomotor screening), modified BESS (Balance error scoring system)


Persistent Post Concussion Symptoms

Physical Cognitive Behavioral/Emotional

Vestibular/Balance

• Headache*• Nausea• Fatigue• Sleep

Disturbance*• Visual

Disturbance*• Neuroendocrin

e Disorders

• Attention*• Memory

Problems*• Poor

Concentration• Delayed

ProcessingSpeed

• Impaired Judgment

• Decreased Executive Functioning

Feeling• Anxious• Depressed*• Agitated• Irritable*• Being

Impulsive

• Dizziness*• Difficulty with

Balance*• Hearing

Difficulties• Tinnitus

*Symptoms in red are the most common after concussion


Clinical Recommendations

1 Military Acute Concussion Evaluation (MACE) and Clinical Management Algorithms

JUN 06DEC 06

2 Cognitive Rehabilitation APR 20093 Driving Following TBI JUL 20094 Indications and Conditions for In-Theater Post-Injury NCAT Testing MAY 20115 Indications & Conditions for Neuroendocrine Dysfunction Screening Post mTBI MAR 20126 Assessment and Management of Dizziness Associated with mTBI SEP 20127 Assessment and Management of Visual Dysfunction Associated with mTBI (in

collaboration with the Vision Center of Excellence)JAN 2013

8 Neuroimaging Following Mild TBI in the Non-Deployed Setting JUL 20139 Progressive Return to Activity Following Acute Concussion/mTBI: Guidance for

the Primary Care Manager in Deployed & Non-deployed SettingsJAN 2014

10 Progressive Return to Activity Following Acute Concussion/mTBI: Guidance for the Rehab. Provider in Deployed & Non-deployed Settings

JAN 2014

11 Management of Sleep Disturbances Following Concussion/mTBI JUN 201412 Management of Headache Following Concussion 2016


Co-Morbid Conditions and Mild TBI

• Sleep disorders• Substance abuse• Psychiatric illness• Vestibular disorders• Visual disorders• Cognitive disorders

Lew, et al: “Prevalence of Chronic Pain, Posttraumatic Stress Disorder, and Persistent Postconcussive Symptoms in OIF/OEF Veterans: Polytrauma Clinical Triad”, Dept. of Veterans Affairs, Journal of Rehabilitative Research and Development, Vol. 46, No. 6, 2009, pp. 697-702, Fig. 1


Gender Differences in TBI Are Getting Attention

Image sources: scientificamerican.com; parents.com; consumerreports.org; reuters.com; ninds.nih.gov


Women and Girls Experience Fewer TBIs Overall

(Faul et al., 2010)

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l“Medically Ready Force…Ready Medical Force” 21

Different Outcomes: Biomechanics and Hormones May Play a Role

∎ Menstrual cycle phase and hormonal contraceptive use may impact symptoms and recovery in women after mTBI. (Wunderle et al., 2014; Gallagher et al., 2018)

∎ Neck stabilizer muscles such as the larger rectus capitis posterior minor may affect symptom severity and recovery time. (Fakhran et al., 2016)

Rectus capitis posterior minor muscles

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Female Sex Hormones: Progesterone

∎ Pre-clinical data shows that progesterone improves experimental TBI outcomes in animals (Brotfain et al., 2016).

∎ Researchers have yet to translate positive results in a large-scale clinical trial. PROTECT III and SYNAPSE showed no benefit (Wright et al.,

2014; Skolnick et al., 2014). Smaller studies have shown improved outcomes (Wright et

al., 2007; Xiao et al., 2008).∎ Effect of gender on mortality after moderate or severe TBI

varies based on age. Female hormones change during menarche, menopause. (Ley et al., 2013; Berry et al., 2009).


Women Report More Symptoms and More Severe Symptoms

Findings in service members, athletes, and civilians show gender differences in reported symptoms after mTBI. (Sufrinko et al., 2016; Brooks et al., 2018; Baker et al., 2016; Bazarian et al., 2010; Brickell et al., 2017)

ON RIGHT: Case-control study of combat mTBI. Women had higher scores on Neurobehavioral Symptom Inventory (NSI) and PTSD Symptom Checklist (PCL) scores.

Neurobehavioral symptom scores, by domain

0

10

20

30

40

50

Arbi

trar

y U

nits Female service members (n = 86)

Male service members (n = 86)

• Error bars are standard deviation.• Data from Brickell et al., 2017; Image source: Anne

Bunner


PTSD May Explain Gender Differences in Service Member Symptoms

∎ Follow-up on previous study. Case-control design with men and women matched on PSTD symptom level, injury severity, etc.

∎ Total post-concussive symptom scores were the same for men and women with the same PTSD status.

∎ Some subgroups of womenreported more somatosensory or vestibular symptoms thanmale counterparts.

∎ Lippa et al 2017

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Female Civilians with TBI at Greater Risk for Major Depressive Disorder (MDD)

∎ Systematic review and meta-analysis examined results from eight studies including 768 civilians with TBI of any severity.

∎Women were just under twice as likely to be diagnosed with MDD after TBI compared to men. (OR 1.72, 95% CI 1.19 to 2.48).

(Cnossen et al., 2017)


Female Veterans Report Intimate Partner Violence and PTSD Symptoms

∎ In a web-based survey of 411 U.S. women veterans, 224 (55%) reported a lifetime history of intimate partner violence (IPV). Higher than civilian rates of 25-33% (Iverson et al.,

2017)∎ Of these, 28% (63 of 224) screened positive for history

of IPV-related TBI.∎ IPV-related TBI was associated with probable post-

traumatic stress disorder (PTSD).

Iverson, Dardis & Pogoda, 2017


Female veterans and intimate partner violence (IPV)

∎ Data from national survey of OEF/OIF/OND veterans who screened positive for lifetime TBI. Included 127 female veterans with complete data.

∎ 63% (80 of 127) reported IPV at some point during their lifetime.

∎ 56% (71 of 127) had a VHA clinician-confirmed diagnosis of TBI.

∎ No association between TBI dx and IPV history.∎ Emotional mistreatment was the most frequently

endorsed IPV experience.

Iverson et al, 2017


Key Takeaways

∎ In the general population, women sustain fewer concussions than men. (Faul et al., 2010)

∎ Female service members, civilians and athletes report a higher number and more severe post-concussion symptoms. (Dick, 2009; Brickell et al., 2016; Bazarian et al., 2010)

∎ Intimate partner violence (IPV)-related TBI is sustained by some women who experience IPV. (Iverson, Dardis, & Pogoda, 2017)

∎ Biomechanics and hormones may play a role in injury risk and recovery outcomes. (Wunderle et al., 2014; Fakhran et al., 2016)

∎ There is limited research in military cohorts examining the role of gender in TBI.


How is DoD Addressing Paucity of Data for Women?

There is limited data on women and TBI, especially in military studies. LTC Chris Ivany, Chief, Army Behavioral Health on April 27, 2017 to House Armed Services Subcommittee on Military Personnel:∎ Women in military have increasing roles across operations.∎ DoD making efforts to evaluate potential gender differences in incidence, symptoms,

and outcomes after mTBI.∎ 15-year longitudinal study already producing results specific to gender.∎ NCAA-DoD Concussion Assessment, Research and Education (CARE) Consortium and

parallel study with Service Academy Cadets seek enrollment of all women at the service academies.

∎ DoD seeking to mitigate limitations in literature by leveraging existing data to examine: gender differences in healthcare utilization, costs; TBI-related comorbidities; and long-term consequences.

∎ DoD funds studies of how gender impacts TBI outcome in service members or Veterans.


Way Forward

∎ Current clinical evidence based on self report measuresBias inherent in self report questionnairesNeed objective data sources

∎ Current female component of armed forces is 16% (Defense Manpower Data Center, 2016)Most studies have under represented female cohortsNeed studies to represent this portion of female

cohorts


Way Forward (continued)

∎Most data discussed in female-focused civilian concussion studies are from females with persistent post concussion symptoms.Need to stratify cohorts into acute and chronic to

elucidate mitigation and treatment factors.


Way Forward (continued 2)

∎Most gender-specific research is focused on neurocognitive and mood related symptomsGender differences in vestibular, visual, and auditory processing

and other areas of sequelae from concussion are current research gaps

∎ PINK Concussions brings researchers together and enables data sharing, collaboration. (PINKconcussions.com, 2017)


References

Baker, J. G., Leddy, J. J., Darling, S. R., Shucard, J., Makdissi, M., & Willer, B. S. (2016). Gender Differences in Recovery From Sports-Related Concussion in Adolescents. Clin Pediatr (Phila), 55(8), 771-775. doi: 10.1177/0009922815606417

Bazarian, J. J., Blyth, B., Mookerjee, S., He, H., & McDermott, M. P. (2010). Sex differences in outcome after mild traumatic brain injury. J Neurotrauma, 27(3), 527-539. doi: 10.1089/neu.2009.1068

Berry, C., Ley, E. J., Tillou, A., Cryer, G., Margulies, D. R., & Salim, A. (2009). The effect of gender on patients with moderate to severe head injuries. J Trauma, 67(5), 950-953. doi: 10.1097/TA.0b013e3181ba3354

Brickell, T. A., Lippa, S. M., French, L. M., Kennedy, J. E., Bailie, J. M., & Lange, R. T. (2016). Female Service Members and Symptom Reporting after Combat and Non-Combat-Related Mild Traumatic Brain Injury. J Neurotrauma. doi: 10.1089/neu.2016.4403

Brooks, B. L., Silverberg, N., Maxwell, B., Mannix, R., Zafonte, R., Berkner, P. D., & Iverson, G. L. (2018). Investigating Effects of Sex Differences and Prior Concussions on Symptom Reporting and Cognition Among Adolescent Soccer Players. Am J Sports Med, 363546517749588. doi: 10.1177/0363546517749588


References

Brotfain, E., Gruenbaum, S. E., Boyko, M., Kutz, R., Zlotnik, A., & Klein, M. (2016). Neuroprotection by Estrogen and Progesterone in Traumatic Brain Injury and Spinal Cord Injury. Curr Neuropharmacol, 14(6), 641-653.

Defense Manpower Data Center. (2016). Active Duty Military Personnel by Service by Rank/Grade.Retrieved from https://www.dmdc.osd.mil/appj/dwp/rest/download?fileName=rg1612_female.pdf&groupName=milRankGrade

Fakhran, S., Qu, C., & Alhilali, L. M. (2016). Effect of the Suboccipital Musculature on Symptom Severity and Recovery after Mild Traumatic Brain Injury. AJNR Am J Neuroradiol. doi: 10.3174/ajnr.A4730

Faul, M., Xu, L., Wald, M., & Coronado, V. G. (2010). Traumatic Brain Injury in the United States: Emergency Department Visits, Hospitalizations and Deaths 2002–2006. Centers for Disease Control and Prevention, Atlanta (GA). Retrieved from http://www.cdc.gov/traumaticbraininjury/pdf/blue_book.pdf

Gallagher, V. T., Kramer, N., Abbott, K., Alexander, J., Breiter, H., Herrold, A., . . . Reilly, J. (2018). The effects of sex differences and hormonal contraception on outcomes following collegiate sports-related concussion. J Neurotrauma. doi: 10.1089/neu.2017.5453


https://www.dmdc.osd.mil/appj/dwp/rest/download?fileName=rg1612_female.pdf&groupName=milRankGrade

http://www.cdc.gov/traumaticbraininjury/pdf/blue_book.pdf

References

Iverson, K. M., Dardis, C. M., & Pogoda, T. K. (2017). Traumatic brain injury and PTSD symptoms as a consequence of intimate partner violence. Compr Psychiatry, 74, 80-87. PMID: 28126481

Iverson, K. M., Sayer, N. A., Meterko, M., Stolzmann, K., Suri, P., Gormley, K., . . . Pogoda, T. K. (2017b). Intimate Partner Violence Among Female OEF/OIF/OND Veterans Who Were Evaluated for Traumatic Brain Injury in the Veterans Health Administration: A Preliminary Investigation. J Interpers Violence, 886260517702491. doi: 10.1177/0886260517702491

Lippa, S. M., Brickell, T. A., Bailie, J. M., French, L. M., Kennedy, J. E., & Lange, R. T. (2017). Postconcussion Symptom Reporting After Mild Traumatic Brain Injury in Female Service Members: Impact of Gender, Posttraumatic Stress Disorder, Severity of Injury, and Associated Bodily Injuries. J Head Trauma Rehabil. doi: 10.1097/HTR.0000000000000353

PINKconcussions.com. (2017). PINK Concussions: Female Concussions via sports, violence, accidents or military service. from http://www.pinkconcussions.com/

Skolnick, B. E., Maas, A. I., Narayan, R. K., van der Hoop, R. G., MacAllister, T., Ward, J. D., . . . Investigators, S. T. (2014). A clinical trial of progesterone for severe traumatic brain injury. N Engl J Med, 371(26), 2467-2476. doi: 10.1056/NEJMoa1411090


http://www.pinkconcussions.com/

References

Stone, S., Lee, B., Garrison, J. C., Blueitt, D., & Creed, K. (2016). Sex Differences in Time to Return-to-Play Progression After Sport-Related Concussion. Sports Health, Epub 2016 Oct 3. PMID: 27697890

Sufrinko, A. M., Mucha, A., Covassin, T., Marchetti, G., Elbin, R. J., Collins, M. W., & Kontos, A. P. (2017). Sex Differences in Vestibular/Ocular and Neurocognitive Outcomes After Sport-Related Concussion. Clin J Sport Med, 27(2), 133-138. doi: 10.1097/JSM.0000000000000324

Wright, D. W., Kellermann, A. L., Hertzberg, V. S., Clark, P. L., Frankel, M., Goldstein, F. C., . . . Stein, D. G. (2007). ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury. Ann Emerg Med, 49(4), 391-402, 402 e391-392. doi: 10.1016/j.annemergmed.2006.07.932

Wright, D. W., Yeatts, S. D., Silbergleit, R., Palesch, Y. Y., Hertzberg, V. S., Frankel, M., . . . Investigators, N. (2014). Very early administration of progesterone for acute traumatic brain injury. N Engl J Med, 371(26), 2457-2466. doi: 10.1056/NEJMoa14043


References

Wunderle, K., Hoeger, K. M., Wasserman, E., & Bazarian, J. J. (2014). Menstrual phase as predictor of outcome after mild traumatic brain injury in women. J Head Trauma Rehabil, 29(5), E1-8. doi: 10.1097/HTR.0000000000000006

Xiao, G., Wei, J., Yan, W., Wang, W., & Lu, Z. (2008). Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial. Crit Care, 12(2), R61. doi: 10.1186/cc6887


Thank you!

Kathy Helmick, M.S,. CRNP, ANP-BC, [email protected]


Documents

Traumatic Brain Injury in Women · Katherine M. Helmick, M.S., CRNP, ANP-BC, CNRN Deputy Director, Defense and Veterans Brain Injury Center (DVBIC)/TBI CoE. J9- Research and Development/Defense