greater severity and functional impact of post-traumatic … · 2020. 5. 12. ·...

1

Greater Severity and Functional Impact of Post-Traumatic Headache in Veterans with Comorbid Neck

Pain following Traumatic Brain Injury

1Shahidi B, 2Bursch RW, 2Carmel JS, 2Carranza AC, 2Cooper KM, 2Lee JV, 2O’Connor CN, 3,5Sorg SF, 2Maluf

KS*, 3-5Schiehser DM*

AFFILIATIONS:

1University of California San Diego, Department of Orthopaedic Surgery

2San Diego State University, Department of Physical Therapy

3Veterans Affairs San Diego Healthcare System, Research Service

4University of California San Diego, Department of Psychiatry

5Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System

*These authors are both designated as senior

FUNDING: NIH R21 NS109852 awarded to DSM, KSM, and BS

. CC-BY-NC-ND 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted May 16, 2020. ; https://doi.org/10.1101/2020.05.12.20099390doi: medRxiv preprint

NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

https://doi.org/10.1101/2020.05.12.20099390

http://creativecommons.org/licenses/by-nc-nd/4.0/

2

ABSTRACT

Purpose/Hypothesis: Traumatic brain injury (TBI) affects 1.7 million people in the U.S. annually, the majority

being mild in severity (mTBI). Post-traumatic headache (PTH) is one of the most common symptoms

experienced after mTBI caused by head or neck trauma and is often refractory to treatment. Although military

Veterans commonly experience mTBI after blast or blunt injuries that likely affect musculoskeletal structures in

the neck, the prevalence of cervical symptoms in Veterans with PTH following mTBI have not been well

characterized. Similarly, the impact of comorbid neck pain on physical and psychosocial functioning in this

population is unknown. This study aims to assess the prevalence of neck pain in Veterans with PTH following

mTBI, and to compare the severity and functional impact of PTH between those with and without comorbid

neck pain.

Number of Subjects: 33 Veterans with PTH after a military-related mTBI were identified from a secondary

analysis of data from a prior study.

Materials and Methods: Participants were determined to have PTH if they responded to questions on the

Patient Headache History Questionnaire (PHHQ), attributed PTH to an accident or injury, and reported PTH in

the TBI history. Individuals with both PTH and comorbid neck pain (PTH+NP) were identified based on an

affirmative response to one or more questions on the PHHQ indicating that HA episodes were either preceded

or accompanied by neck pain. Standardized measures of HA severity and frequency, insomnia, fatigue, mood

disorders (Depression, Anxiety, and Posttraumatic Stress Disorder), and physical and emotional role function

(SF-36) were compared between groups with and without comorbid neck pain.

Results: Of the 33 participants with PTH, 22 (67%) also had neck pain. There were no differences in

demographic or TBI-specific characteristics between groups (p>0.069). Sixty-three percent of the PTH+NP

group reported severe or incapacitating HA, compared to 27% of those with PTH alone (P=0.049). Insomnia

severity and fatigue were significantly greater in the PTH+NP group (P<0.040), and physical function due to

bodily pain and physical role function was significantly lower in the PTH+NP group (P<0.036). There were no

significant differences between groups for any of the mood or emotional-role functioning scales (P>0.326).



https://doi.org/10.1101/2020.05.12.20099390


3

Conclusions: The majority of Veterans with mTBI and PTH reported comorbid neck pain. Veterans with PTH

and NP reported increased severity of HA, insomnia, fatigue, and a greater physical, but not emotional

functional limitations compared to those without NP.

INTRODUCTION

Approximately 1.7 million people in the United States require medical attention for traumatic brain

injury (TBI) every year, with mild TBI (mTBI) being the most prevalent.1 Commonly reported symptoms of

mTBI include headaches, musculoskeletal pain, fatigue, mood and sleep disturbances, and cognitive

impairments. These symptoms are refractory to treatment in nearly half of those who sustain a mTBI,

developing into a chronic post-concussive syndrome (PCS) that can persist for years after the traumatic injury2.

Persistent post-traumatic headache (PTH), defined as a head injury-induced headache lasting greater than 3

months duration,3 is the most common symptom of PCS, with prevalence rates averaging 55%-60% across

studies.4,5

Military service members and veterans are a population with high risk of exposure to TBI, with nearly

40% of those with TBI reporting PTH .6-8 In this population, blast-related injuries are the most common cause

of TBI due to high exposure to combat and artillery.9 One often overlooked feature of blast injury-induced TBI

is concurrent damage to surrounding tissues such as cervical musculoskeletal structures that in many ways

resembles whiplash injury.10 In fact, neck injury is one of the leading causes of medical evacuation of military

personnel from US operations.11 Although prior literature is sparse on the relationship between neck injury and

PTH in the veteran population, the negative impact of concurrent neck injury and headache symptoms has been

well established in the civilian population.12 For example, the presence of comorbid neck pain with migraine

has been shown to be a significant predictor of disability and is associated with increased headache frequency,

intensity and duration.13,14 In addition, those who experience migraine or PTH report higher rates of concurrent

neck pain than those without.11,13-18

One clinical barrier to recovery in those with PTH is that high quality evidence to guide specific

interventions is lacking. For example, treatments for both PTH and migraine headaches include a wide



https://doi.org/10.1101/2020.05.12.20099390


4

spectrum of interventions including pharmacological management, nerve blocks, neurostimulation, physical

therapy, injections, and even surgery10,11. Clinically, PTH often resembles migraine in its presentation, and is

therefore managed similarly despite differing mechanisms19. As such, it is not surprising that clinical outcomes

of PTH treatment are highly variable and suboptimal11.

Investigating the influence of comorbid neck pain on physical and emotional functioning among

veterans with PTH is necessary to inform clinical management of PTH, and fills an important gap in the

literature addressing the military population. In this study, we aim to compare the severity and functional

impact of PTH in US Veterans with and without comorbid neck pain following mTBI. We hypothesize that

those with PTH and comorbid neck pain will present with greater headache impairments and reduced physical

and emotional functioning as compared to those without neck pain.

METHODS

Participants

This was a secondary analysis of a database from a prior study20. The database included 257 military

veterans with and without TBI who were recruited at the VA San Diego Healthcare System (VASDHS) from

2010 to 2014 via outpatient clinics, recruitment flyers, and by word of mouth. The participants included in this

database predominantly served in Iraq and Afghanistan conflicts, including Operation Enduring Freedom

(OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND). The database contains a compilation

of various patient reported questionnaires and neuropsychological outcome measures. Since the current analyses

represent a retrospective subsample from a larger study, the sample size was determined based on completion of

questionnaires of interest. The VASDHS institutional review board approved the study and all participants

provided informed consent.

An eligibility screening was conducted on all participants prior to study enrollment21. Participant

demographics, as well as relevant military and medical history, were collected in a clinical interview. During

this interview, details regarding both military (i.e., active duty) and non-military (i.e., prior to or following

military discharge) related head injuries were obtained using a modified version of the VA Semi-Structured

Clinical Interview for TBI22. For those reporting one or more TBIs, additional information was gathered about



https://doi.org/10.1101/2020.05.12.20099390


5

the number of TBIs, months since most recent TBI, and mechanism of each TBI injury (i.e., blunt vs. blast).

Participants were excluded if they expressed current suicidal and/or homicidal ideation, intent, or plan; had a

current or previous diagnosis of a severe mental disorder (e.g. schizophrenia, bipolar disorder); had a history of

significant neurological medical conditions such as epilepsy or multiple sclerosis; or reported current substance

abuse or dependence as determined by initial diagnostic clinical interview and verified by a Rapid Response 10-

drug Test Panel and toxicology screening.

Participants were included in the present study only if they met the following self-report criteria for mild

TBI as defined by the Department of Veterans Affairs and Department of Defense21: (1) loss of consciousness

(LOC) ≤ 30 minutes, (2) alteration of consciousness (AOC) ≤ 24 hours, and/or (3) post-traumatic amnesia

(PTA) ≤ 24 hours. Participants were further included if they reported headaches after experiencing a TBI in the

clinical interview and completed the Baylor Health Patient Headache History Questionnaire (PHHQ)23. This

clinical questionnaire collected information on headache severity, frequency, duration, and location, as well as

associated neck pain symptoms. Participants in the cohort were split into two groups based on presence

(PTH+NP) or absence (PTH) of comorbid neck pain. Individuals with both PTH and comorbid neck pain

(PTH+NP) were identified based on an affirmative response to one or more questions on the PHHQ indicating

that headache episodes were either preceded or accompanied by neck pain (Figure 1). Patient demographics

included age, sex, ethnicity, marital status, years of education, military branch, and employment status.

Figure 1. Selection criteria for PTH and PTH+NP study groups sampled from existing Veteran research database. PTH = Post-traumatic headache;’ TBI=Traumatic Brain Injury; PHHQ = Patient Headache History Questionnaire.



https://doi.org/10.1101/2020.05.12.20099390


6

Outcome Measures

Headache Impairment Measures

Headache characteristics were assessed using individual survey items from the PHHQ. Due to the

small sample size and large number of response options for individual items in this clinical questionnaire,

responses were collapsed into dichotomous outcomes for headache severity, frequency, and duration. Three

response categories characterized headache location. Severity of headaches was assessed by the PHHQ

question “My headaches if I don’t treat them effectively are usually…” with response options of 1) mild or

moderate, or 2) severe or incapacitating. Frequency of headaches was assessed by the PHHQ question “My

headaches usually occur…” with response options of 1) daily or weekly, or 2) less frequent than weekly.

Duration of headaches was assessed by the PHHQ question “My headaches if I don’t take medication will

usually last…” with response options of 1) less than 1 day, or 2) more than 1 day. Headache location was

assessed by the PHHQ question “My headaches occur…” with response options of 1) only on one side at a time,

2) as a band around my head, or 3) over my entire head.

Physical Health Measures

Measures of physical health and function included insomnia, fatigue, general health, bodily pain,

physical functioning, and physical role limitations. Sleep was measured using the Insomnia Severity Index

(ISI), which is a 7-item questionnaire that quantifies the severity of insomnia with excellent reliability and

internal consistency and has been validated in veterans with a history of TBI.24,25 ISI scores range from 0-28

pts, with ≥11 points indicating clinically significant insomnia. Fatigue was measured using the Modified

Fatigue Impact Scale (MFIS), which is a 29-item questionnaire ranging from 0-84 points that assesses the

impact of fatigue on cognitive, physical, and psychosocial functioning and has been validated in veterans with

mTBI26,27. A threshold of 38 or more points has been suggested to represent clinically significant

fatigue28. Physical health was measured using physical health subscales of the Short Form Health Survey (SF-

36). The SF-36 is a 36-item quality of life survey that determines patient health status with physical health

subscales including general health, bodily pain, physical functioning, and physical role limitations, and mental

health subscales including mental health, vitality, social functioning, and emotional role limitations. Each of



https://doi.org/10.1101/2020.05.12.20099390


7

the 8 subscales are scored separately and range from 0-100, with higher scores indicating better health and

lower scores indicating more limitation.29

Emotional Health Measures

Emotional health metrics assessed depression, anxiety, post-traumatic stress, mental health, vitality,

social functioning, and emotional role limitations. Depression and anxiety were assessed using the Beck

Depression Inventory (BDI) and Beck Anxiety Inventory (BAI), respectively. The BDI is a 21-item self-report

questionnaire with good reliability and validity that is scored on a scale from 0-63 points. The BDI has been

recommended for evaluation of depression in the TBI population.30,31 Established score ranges for interpreting

the severity of depression are as follows; 17-20 points indicates borderline clinical depression, 21-30 points

indicates moderate depression, and over 40 points indicates severe depression.32 The BAI is a 21-item self-

report questionnaire with excellent reliability and validity.33 It is scored on a scale of 0-63 points, with scores

over 36 points indicating high levels of anxiety, and scores below 21 points indicating low anxiety.33 Presence

and severity of Post-traumatic Stress Disorder (PTSD) were measured using the Post-traumatic Stress Disorder

Checklist (PCL) Military Version. The PCL is a 17-item self-report measure that is scored on a scale from 0-85

points, with scores above 50 points indicating clinically significant PTSD34. Mental health, vitality, social

functioning, and emotional role limitations were calculated from the mental health subscales of the SF-36 as

described above.

Statistical Analysis

Independent t-tests were used to compare means between PTH and PTH+NP groups for continuous

variables. Chi square or fisher exact tests were used to compare proportions between groups for categorical

variables. P values of 0.05 were considered significant, and P values of less than 0.08 were considered a trend.

Data were examined for outliers and checked for normality. All statistical analyses were performed on SPSS

software version 25 (IBM Corp., 2019).

RESULTS

Participant Characteristics



https://doi.org/10.1101/2020.05.12.20099390


8

A total of 33 participants met the inclusion criteria for this study, with the majority (N=22, 66.7%)

reporting concurrent neck pain. Participant characteristics are detailed in Table 1. The majority of participants

were Caucasian (57.6%), with no significant difference in the ethnic distribution between groups (P=0.196).

The veteran cohort was predominantly male (84.8%), with no significant difference in sex between groups (P =

0.144). The PTH+NP group tended to have more Navy veterans as compared to the PTH group (P=0.069). Just

over half of the cohort was employed (51.5%), with no differences in marital status (P=0.197), education

(P=0.792), or employment status between groups (P = 0.805). The PTH+NP group tended to report a greater

number of mTBIs compared to the PTN group (P = 0.071), with no differences in time since injury, injury

mechanism, or mTBI diagnostic criteria characteristics (P ≥ 0.181).

Table 1. Participant demographic and clinical characteristics. Values reported as mean (SD) or N (% group total). PTH= Post-traumatic headache, NP = Neck Pain. *Individuals may have experienced multiple mTBI criteria simultaneously.



https://doi.org/10.1101/2020.05.12.20099390


9

Headache Impairments

Headache severity was greater in the PTH+NP group than the PTH group (P = 0.049), with the majority

of participants with concurrent neck pain reporting severe or incapacitating headaches and those without

headaches reporting only mild or moderate headaches. There were no differences in headache duration or

frequency between groups (P ≥ 0.231), and no clear pattern emerged for differences in headache location

between those with and without concurrent neck pain (Table 2).

Table 2. Headache characteristics in participants with and without concurrent neck pain

Physical Health Measures

Severity of insomnia was higher in the PTH+NP group with those reporting comorbid neck pain

indicating clinically relevant insomnia of (17.5 ± 6.3), as compared to the PTH+NP group (9.4 ± 7.6; P = 0.003,

Figure 2A). On average, fatigue levels in the PTH+NP group exceeded the threshold for clinically relevant

fatigue (44.8 ± 22.3) and were significantly higher than the PTH group (21.2 ± 35.7; P = 0.040, Figure 2B). The



https://doi.org/10.1101/2020.05.12.20099390


10

PTH+NP group reported lower physical function due to bodily pain (42.2 ± 24.2) than the PTH group (67.7 ±

28.8; P = 0.012, Figure 2C), and lower physical-health related role function (27.3 ± 38.5) than the PTH group

(59.1 ± 40.7; P = 0.036, Figure 2D). SF-36 general health (P = 0.389) did not differ between groups, and there

was a trend for reduced physical functioning (P = 0.084) in the PTH+NP group.

Figure 2: Bars indicate mean (SD) scores for the post-traumatic headache with neck pain (PTH+NP, N=22) and PTH with no neck pain (PTH, N=11) groups. A. Insomnia Severity Index (ISI) scores range from 0-28, with higher scores indicating increased insomnia severity. B. Modified Fatigue Impact Scale Scores range from 0-84, with higher scores indicating increased fatigue. C. SF-36 Bodily Pain domain scores, with lower scores indicating lower physical ability due to bodily pain. D. SF-36 Physical Role Function domain scores, with lower scores indicating lower physical role functioning. (**P<0.01, *P<0.05)

Emotional Health Measures



https://doi.org/10.1101/2020.05.12.20099390


11

There were no significant differences in mood-related measures of depression (BDI, P = 0.326), anxiety

(BAI, P = 0.928), or PTSD (PCL, P = 0.587) between groups. Similarly, there were no group differences in the

SF-36 Mental Health subscale (PTH+NP = 50.2 ± 19.4; PTH = 56.7 ± 26.9; P = 0.429; Figure 3A), or role

limitations related to emotional health as measured by the SF-36 Role Emotional subscale (PTH+NP = 36.4 ±

41.0; PTH = 51.5 ± 45.6; P = 0.343, Figure 3B). SF-36 Vitality (P = 0.389) and Social Functioning (P = 0.985)

subscale scores were also similar between groups.

Figure 3. Bars indicate mean (SD) scores for the post-traumatic headache with neck pain (PTH+NP, N=22) and PTH with no neck pain (PTH, N=11) groups. A. SF-36 Mental Health domain scores, with lower scores indicating lower mental health. B. SF-36 Emotional Role domain scores, with lower scores indicating lower emotional role functioning. All scores range from 0-100 points, with no significant differences between groups (P>0.05).

DISCUSSION

The majority of veterans with mTBI and PTH in our sample experienced concurrent neck pain that was

associated with more severe headaches, insomnia, and fatigue, as well as greater physical limitations due to

bodily pain and reduced physical role functioning compared to those without neck pain. Importantly, these

physical limitations occurred despite similar mood profiles and emotional functioning between groups. Overall,

these findings support our hypothesis that veterans with PTH and comorbid neck pain experience more severe

headaches and subsequent physical limitations, but are contrary to our hypothesis regarding the relationship



https://doi.org/10.1101/2020.05.12.20099390


12

between comorbid neck pain and emotional functioning. This is the first study to show that comorbid neck pain

negatively impacts headache symptoms and physical role functioning in veterans with PTH following mTBI.

Despite the limited size of our cohort, the prevalence rate of 66.7% for comorbid neck pain is consistent

with prevalence rates for neck pain reported in larger samples. One paper investigating the prevalence of

chronic musculoskeletal pain in civilians after mTBI reported that 59.6% of individuals reported neck or

shoulder pain of greater than 6 month duration35, and another study reported a neck pain prevalence rate of

41.7% in military veterans4. These rates mirror the prevalence of comorbid neck in primary headache disorders

such as migraine, where prevalence rates are reported to range between 40%-76%.13,14,16 To our knowledge, no

previous study reporting neck pain prevalence rates in individuals with mTBI has compared health or function

between those with and without this common comorbidity.

The relationship between neck pain and headache impairments has not been well elucidated in the TBI

population. Existing studies suggest that the majority of individuals with mTBI experience headaches on a daily

basis, and headache severities are moderate, with average numerical pain rating scores ranging from 4 to 6 on a

10-point scale.4,35 Our data indicate that the majority of individuals with comorbid neck pain reported severe or

incapacitating headaches compared to only mild or moderate severity in those without, suggesting that neck

pain significantly compounds headache symptom intensity in this population. Despite this difference in

symptom intensity, we found no influence of neck pain on headache frequency or duration, which is in contrast

to studies of migraine reporting positive correlations between neck pain or neck pain related disability and

headache frequency13,14,36

One interesting finding of our study was that the location of headache was non-specific in our PTH

population and did not differ between groups. Primary and cervicogenic headaches are often closely tied to neck

pain. Cervicogenic headache typically presents with unilateral symptoms and is by definition caused by a

disorder of the cervical spine and its component bony, disc and/or soft tissue elements.3,37 A similar presentation

in the PTH+NP group would suggest that similar treatment approaches targeting cervical pain generators may

be indicated for both PTH and cervicogenic headaches. However, the variation in phenotype observed here

suggests the need for a different clinical approach, and perhaps supports the current clinical practice to treat



https://doi.org/10.1101/2020.05.12.20099390


13

PTH similarly to migraine headaches which are thought to be centrally mediated. Elevated fatigue and

insomnia in the PTH+NP group support the hypothesis that comorbid neck pain may result from heightened

central sensitivity in some individuals with mTBI and PTH38. Although there is some evidence that impaired

descending pain modulation may contribute to PTH39, future studies are needed to identify the relative

contribution of peripheral and central mechanisms to greater symptom severity among those with PTH and

comorbid neck.

Where the influence of comorbid neck pain on headache impairments seems to be variable-dependent,

its influence on overall physical health and ability is clear, and mirrors findings from studies in other headache

populations. In the TBI population, sleep disturbances are common; occurring in nearly half of individuals, with

effects lasting from months to years after the original injury and increasing with injury severity.40-46 Similar

relationships exist in individuals with persistent headaches47,48, and even chronic neck pain.49 As such, it is not

surprising that our results reflect that a combination of mTBI, headache, and neck pain produces a more severe

phenotype than any given symptom in isolation. Closely related to insomnia, fatigue is another symptom

strongly established among those with mTBI that can persist for months or years following the injury.45,50,51

Fatigue has been shown to be a strong predictor for disability in the TBI population.52 Moreover, those with

neck pain of any source tend to report higher levels of fatigue when compared to their asymptomatic

counterparts.53 These relationships also extend to overall disability, although the literature is mixed in this

regard. The presence of neck pain has been shown to be significantly associated with physical impairments

(mobility and strength)54 as well as disability in individuals with migraine headaches,14,36 while other research

has failed to demonstrate a significant influence on participation restrictions such as missing days of work or

social events.54 Although these data are largely limited to populations that are unrelated to mechanisms

including trauma, the trend in the literature towards increased physical disability among those with neck pain

coincides with our findings of overall reduced ability on the SF-36 physical health subscales.

Interestingly, our findings related to mood and emotional health did not distinguish between groups.

This was surprising given the tendency for a greater number of head injuries in the PTH+NP group, which has

previously been shown to correlate with the severity of mood disturbances55. This finding was also contrary to



https://doi.org/10.1101/2020.05.12.20099390


14

our initial hypothesis given that psychological and emotional health impairments are widely observed in the

mTBI population20, as well as in those with headaches and neck pain56-59. Despite the lack of group differences,

our data show that both groups demonstrated clinically relevant levels of anxiety and depression, as well as

reduced mental health and emotional role functioning. The similarity of mood and emotional health ratings

between groups suggest that differences observed in headache severity and physical health domains were not

confounded by differences in emotional health or a tendency of the PTH+NP group to endorse greater distress

generally. The lack of a direct relationship between psychological and physical symptomology has been

recognized in recent literature in the mTBI population, suggesting that these factors may be independently

modulated5,60.

Study Limitations

This study had a number of limitations, primarily that the sample size was small due to the secondary

nature of our analysis. Despite the small size of this sample, it is comparable to other studies of PTH in mTBI

populations evaluating impairment-based measures and physical health, and the ability to distinguish statistical

differences between groups for a number of our outcomes suggests sufficient power for our comparisons of

interest. Additionally, our retrospective analysis of an existing database resulted in a lack of prospectively

defined variables of interest. As such, our operational definition of neck pain was based on a small set of

questions from the PHHQ, which limited our ability to characterize the nature and severity of neck pain

symptoms. Additionally, causal inferences cannot be determined from a cross-sectional study design. Future

research is needed to prospectively evaluate the mechanisms and impact of comorbid neck pain on headache

impairments, physical, and emotional health in this population.

CONCLUSION

Neck pain is a common comorbidity of PTH and one that has several functional implications. In this

sample of veterans with mTBI and PTH, those with comorbid neck pain experienced greater headache severity

and poorer physical health and role functioning, despite no differences in emotional health compared to those

without comorbid neck pain. Awareness of these associated impairments may be a valuable contribution to

direct future research and clinical practices. Further research that prospectively investigates the mechanisms and



https://doi.org/10.1101/2020.05.12.20099390


15

impact of comorbid neck pain on headache impairments, physical and psychosocial functioning is needed in this

population, specifically with regard to directing targeted treatment approaches.

REFERENCES

1. Theeler B, Lucas S, Riechers RG, 2nd, Ruff RL. Post-traumatic headaches in civilians and military

personnel: a comparative, clinical review. Headache. 2013;53(6):881-900.

2. Schwab K, Terrio HP, Brenner LA, et al. Epidemiology and prognosis of mild traumatic brain injury in

returning soldiers: A cohort study. Neurology. 2017;88(16):1571-1579.

3. Headache Classification Committee of the International Headache S. The International Classification of

Headache Disorders, 3rd edition. Cephalalgia. 2013;33(9):629-808.

4. King PR, Beehler GP, Wade MJ. Self-Reported Pain and Pain Management Strategies Among Veterans

With Traumatic Brain Injury: A Pilot Study. Mil Med. 2015;180(8):863-868.

5. Nampiaparampil DE. Prevalence of chronic pain after traumatic brain injury: a systematic review.

JAMA. 2008;300(6):711-719.

6. Jouzdani SR, Kaka G. EHMTI-0023. Characteristics of post-traumatic headache following mild

traumatic brain injury in military personnel in Iran. The Journal of Headache and Pain. 2014;15(S1).

7. Larsen EL, Ashina H, Iljazi A, et al. Acute and preventive pharmacological treatment of post-traumatic

headache: a systematic review. J Headache Pain. 2019;20(1):98.

8. Lazarus R, Helmick K, Malik S, Gregory E, Agimi Y, Marion D. Continuum of the United States

military's traumatic brain injury care: adjusting to the changing battlefield. Neurosurg Focus.

2018;45(6):E15.

9. Rosenfeld JV, McFarlane AC, Bragge P, Armonda RA, Grimes JB, Ling GS. Blast-related traumatic

brain injury. The Lancet Neurology. 2013;12(9):882-893.

10. Conidi FX. Interventional Treatment for Post-traumatic Headache. Curr Pain Headache Rep.

2016;20(6):40.



https://doi.org/10.1101/2020.05.12.20099390


16

11. Cohen SP, Kapoor SG, Nguyen C, et al. Neck pain during combat operations: an epidemiological study

analyzing clinical and prognostic factors. Spine (Phila Pa 1976). 2010;35(7):758-763.

12. Bogduk N, Govind J. Cervicogenic headache: an assessment of the evidence on clinical diagnosis,

invasive tests, and treatment. The Lancet Neurology. 2009;8(10):959-968.

13. Calhoun AH, Ford S, Millen C, Finkel AG, Truong Y, Nie Y. The prevalence of neck pain in migraine.

Headache. 2010;50(8):1273-1277.

14. Ford S, Calhoun A, Kahn K, Mann J, Finkel A. Predictors of disability in migraineurs referred to a

tertiary clinic: neck pain, headache characteristics, and coping behaviors. Headache. 2008;48(4):523-

528.

15. Ashina S, Bendtsen L, Lyngberg AC, Lipton RB, Hajiyeva N, Jensen R. Prevalence of neck pain in

migraine and tension-type headache: a population study. Cephalalgia. 2015;35(3):211-219.

16. Lampl C, Rudolph M, Deligianni CI, Mitsikostas DD. Neck pain in episodic migraine: premonitory

symptom or part of the attack? J Headache Pain. 2015;16:566.

17. Romesser J, Booth J, Benge J, Pastorek N, Helmer D. Mild traumatic brain injury and pain in Operation

Iraqi Freedom/Operation Enduring Freedom veterans. The Journal of Rehabilitation Research and

Development. 2012;49(7).

18. Uomoto JM, Esselman PC. Traumatic Brain Injury and Chronic Pain - Differential Types and Rates by

Head-Injury Severity. Arch Phys Med Rehab. 1993;74(1):61-64.

19. Capi M, Pomes LM, Andolina G, Curto M, Martelletti P, Lionetto L. Persistent Post-Traumatic

Headache and Migraine: Pre-Clinical Comparisons. Int J Environ Res Public Health. 2020;17(7).

20. Bomyea J, Lang AJ, Delano-Wood L, et al. Neuropsychiatric Predictors of Post-Injury Headache After

Mild-Moderate Traumatic Brain Injury in Veterans. Headache. 2016;56(4):699-710.

21. Management of Concussion/mTBI Working Group. VA/DoD Clinical Practice Guideline for

Management of Concussion/Mild Traumatic Brain Injury. Journal of Rehabilitation Research &

Development. 2009;46(6):Cp1-68.



https://doi.org/10.1101/2020.05.12.20099390


17

22. Vanderploeg RD, Groer S, Belanger HG. Initial developmental process of a VA semistructured clinical

interview for TBI identification. J Rehabil Res Dev. 2012;49(4):545-556.

23. Center BN. Patient Headache History Questionnaire. 2012;

https://www.baylorhealth.com/SiteCollectionDocuments/Documents_Dallas/Headache%20Center/Patie

nt%20Headache%20History%20Questionnaire.pdf, 2019.

24. Vegar Z, Hussain M. Validity and reliability of insomnia severity index and its correlation with

pittsburgh sleep quality index in poor sleepers among Indian university students. Int J Adolesc Med

Health. 2017.

25. Kaufmann CN, Orff HJ, Moore RC, Delano-Wood L, Depp CA, Schiehser DM. Psychometric

Characteristics of the Insomnia Severity Index in Veterans With History of Traumatic Brain Injury.

Behav Sleep Med. 2019;17(1):12-18.

26. Juengst S, Skidmore E, Arenth PM, Niyonkuru C, Raina KD. Unique contribution of fatigue to disability

in community-dwelling adults with traumatic brain injury. Arch Phys Med Rehabil. 2013;94(1):74-79.

27. Schiehser DM, Delano-Wood L, Jak A, et al. Validation of the Modified Fatigue Impact Scale in mild to

moderate traumatic brain injury. . J Head Trauma Rehabil. 2015;30(2):116-121.

28. Flachenecker P, Kumpfel T, Kallmann B, et al. Fatigue in multiple sclerosis: a comparison of different

rating scales and correlation to clinical parameters. Mult Scler. 2002;8(6):523-526.

29. Ware JE, Jr., Gandek B. Overview of the SF-36 Health Survey and the International Quality of Life

Assessment (IQOLA) Project. J Clin Epidemiol. 1998;51(11):903-912.

30. Beck A, Steer R, Carbin M. Psychometric properties of the Beck Depression Inventory: Twenty-five

years of evaluation. Clinical Psychology Review. 1988;8(1):77-100.

31. Zaninotto AL, Vicentini JE, Fregni F, et al. Updates and Current Perspectives of Psychiatric

Assessments after Traumatic Brain Injury: A Systematic Review. Front Psychiatry. 2016;7:95.

32. Beck A, Steer R, Brown G. Manual for the Beck depression inventory-II (BDI-II). 1996.

33. Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: psychometric

properties. J Consult Clin Psychol. 1988;56(6):893-897.



https://doi.org/10.1101/2020.05.12.20099390


18

34. McDonald SD, Calhoun PS. The diagnostic accuracy of the PTSD checklist: a critical review. Clin

Psychol Rev. 2010;30(8):976-987.

35. Lahz S, Bryant RA. Incidence of chronic pain following traumatic brain injury. Arch Phys Med Rehabil.

1996;77(9):889-891.

36. Florencio L, Chaves T, Carvalho G, et al. Neck pain disability is related to frequency of migraine

attacks: a cross-sectional study. Headache. 2014;54(7):1203-1210.

37. Biondi D. Cervicogenic Headache: A Review of Diagnostic and Treatment Strategies. Journal of the

American Osteopathic Association. 2005;105:16S-22S.

38. Ruff RL, Blake K. Pathophysiological links between traumatic brain injury and post-traumatic

headaches. F1000Res. 2016;5.

39. Defrin R, Riabinin M, Feingold Y, Schreiber S, Pick CG. Deficient pain modulatory systems in patients

with mild traumatic brain and chronic post-traumatic headache: implications for its mechanism. J

Neurotrauma. 2015;32(1):28-37.

40. Aoun R, Rawal H, Attarian H, Sahni A. Impact of traumatic brain injury on sleep: an overview. Nat Sci

Sleep. 2019;11:131-140.

41. Baumann CR, Werth E, Stocker R, Ludwig S, Bassetti CL. Sleep-wake disturbances 6 months after

traumatic brain injury: a prospective study. Brain. 2007;130(Pt 7):1873-1883.

42. Kempf J, Werth E, Kaiser PR, Bassetti CL, Baumann CR. Sleep-wake disturbances 3 years after

traumatic brain injury. J Neurol Neurosurg Psychiatry. 2010;81(12):1402-1405.

43. Mollayeva T, Pratt B, Mollayeva S, Shapiro CM, Cassidy JD, Colantonio A. The relationship between

insomnia and disability in workers with mild traumatic brain injury/concussion: Insomnia and disability

in chronic mild traumatic brain injury. Sleep Med. 2016;20:157-166.

44. Bryan CJ. Repetitive traumatic brain injury (or concussion) increases severity of sleep disturbance

among deployed military personnel. Sleep. 2013;36(6):941-946.

45. Schiehser DM, Delano-Wood L, Jak AJ, et al. Predictors of cognitive and physical fatigue in post-acute

mild-moderate traumatic brain injury. Neuropsychol Rehabil. 2017;27(7):1031-1046.



https://doi.org/10.1101/2020.05.12.20099390


19

46. Orff HJ JA, Gregory AM, Colón CC, Schiehser DM, Drummond SPA, Lohr JB, Twamley EW. Sleep

Disturbance, Psychiatric, and Cognitive Functioning in Veterans with Mild to Moderate Traumatic Brain

Injury. J Sleep Disor Treat Care. 2015;4(2).

47. Tkachenko N, Singh K, Hasanaj L, Serrano L, Kothare SV. Sleep Disorders Associated With Mild

Traumatic Brain Injury Using Sport Concussion Assessment Tool 3. Pediatr Neurol. 2016;57:46-50 e41.

48. Jaramillo CA, Eapen BC, McGeary CA, et al. A cohort study examining headaches among veterans of

Iraq and Afghanistan wars: Associations with traumatic brain injury, PTSD, and depression. Headache.

2016;56(3):528-539.

49. Kim SH, Lee DH, Yoon KB, An JR, Yoon DM. Factors Associated with Increased Risk for Clinical

Insomnia in Patients with Chronic Neck Pain. Pain Physician. 2015;18(6):593-598.

50. Ahman S, Saveman BI, Styrke J, Bjornstig U, Stalnacke BM. Long-term follow-up of patients with mild

traumatic brain injury: a mixed-method study. J Rehabil Med. 2013;45(8):758-764.

51. Norrie J, Heitger M, Leathem J, Anderson T, Jones R, Flett R. Mild traumatic brain injury and fatigue: a

prospective longitudinal study. Brain Inj. 2010;24(13-14):1528-1538.

52. Juengst S, Skidmore E, Arenth P, Niyonkuru C, Raina K. Unique contribution of fatigue to disability in

community-dwelling adults with traumatic brain injury. Arch Phys Med Rehabil. 2013;94(1):74–79.

53. Takasaki H, Treleaven J. Construct validity and test-retest reliability of the Fatigue Severity Scale in

people with chronic neck pain. Arch Phys Med Rehabil. 2013;94(7):1328-1334.

54. Bragatto MM, Bevilaqua-Grossi D, Benatto MT, et al. Is the presence of neck pain associated with more

severe clinical presentation in patients with migraine? A cross-sectional study. Cephalalgia.

2019;39(12):1500-1508.

55. Cole WR, Bailie JM. Neurocognitive and Psychiatric Symptoms following Mild Traumatic Brain Injury.

In: Laskowitz D, Grant G, eds. Translational Research in Traumatic Brain Injury. Boca Raton

(FL)2016.

56. van der Naalt J, Timmerman ME, de Koning ME, et al. Early predictors of outcome after mild traumatic

brain injury (UPFRONT): an observational cohort study. Lancet Neurol. 2017;16(7):532-540.



https://doi.org/10.1101/2020.05.12.20099390


20

57. Ma HP, Chen PS, Wong CS, et al. Psychometric Evaluation of Anxiety, Depression, and Sleep Quality

after a Mild Traumatic Brain Injury: A Longitudinal Study. Behav Neurol. 2019;2019:4364592.

58. Wang SJ, Juang KD. Psychiatric comorbidity of chronic daily headache: impact, treatment, outcome,

and future studies. Curr Pain Headache Rep. 2002;6(6):505-510.

59. Ortego G, Villafane JH, Domenech-Garcia V, Berjano P, Bertozzi L, Herrero P. Is there a relationship

between psychological stress or anxiety and chronic nonspecific neck-arm pain in adults? A systematic

review and meta-analysis. J Psychosom Res. 2016;90:70-81.

60. Kuperman P, Granovsky Y, Granot M, et al. Psychophysic-psychological dichotomy in very early acute

mTBI pain: A prospective study. Neurology. 2018;91(10):e931-e938.



https://doi.org/10.1101/2020.05.12.20099390
