Natural History of Headache after Traumatic Brain Injury
Jeanne M. Hoffman,1Sylvia Lucas,2Sureyya Dikmen,1,3,4Cynthia A. Braden,5
Allen W. Brown,6Robert Brunner,7Ramon Diaz-Arrastia,8William C. Walker,9
Thomas K. Watanabe,10and Kathleen R. Bell1
Headache is one of the most common persisting symptoms after traumatic brain injury (TBI). Yet there is a
paucity of prospective longitudinal studies of the incidence and prevalence of headache in a sample with a range
of injury severity. We sought to describe the natural history of headache in the first year after TBI, and to
determine the roles of prior history of headache, sex, and severity of TBI as risk factors for post-traumatic
headache. A cohort of 452 acute, consecutive patients admitted to inpatient rehabilitation services with TBI were
enrolled during their inpatient rehabilitation from February 2008 to June 2009. Subjects were enrolled across 7
acute rehabilitation centers designated as TBI Model Systems centers. They were prospectively assessed by
structured interviews prior to inpatient rehabilitation discharge, and at 3, 6, and 12 months after injury. Results
of this natural history study suggest that 71% of participants reported headache during the first year after injury.
The prevalence of headache remained high over the first year, with more than 41% of participants reporting
headache at 3, 6, and 12 months post-injury. Persons with a pre-injury history of headache (p<0.001) and
females (p<0.01) were significantly more likely to report headache. The incidence of headache had no relation to
TBI severity (p=0.67). Overall, headache is common in the first year after TBI, independent of the severity of
injury range examined in this study. Use of the International Classification of Headache Disorders criteria
requiring onset of headache within 1 week of injury underestimates rates of post-traumatic headache. Better
understanding of the natural history of headache including timing, type, and risk factors should aid in the design
of treatment studies to prevent or reduce the chronicity of headache and its disruptive effects on quality of life.
Key words: headache; natural history; traumatic brain injury
et al., 2010; Packard, 2005). Awareness of TBI-related symp-
toms, including headache, has increased as attention is fo-
cused on concussion or mild TBI sustained in sports injuries
(Makdissi et al., 2010; Pellman et al., 2004), and as a result of
the military conflicts in Iraq and Afghanistan (Hoge et al.,
2008). While the mechanism of post-traumatic headache
(PTH) remains poorly understood, it is classified as a sec-
ondary headache syndrome in the International Classification
of Headache Disorders, 2nd edition (ICHD; The International
eadache is one of the most commonly reported symp-
toms following traumatic brain injury (TBI; Dikmen
Classification of Headache Disorders, 2004). Classification is
primarily based on time of onset after injury or regaining
consciousness (within 7 days), and chronicity of headache
based on duration of headache lasting less than or greater
than 3 months (acute versus chronic). However, several
studies have reported a longer latency between injury and
PTH and a higher incidence of chronic PTH than one would
expect based on the ICHD definition (Martins et al., 2009;
Theeler and Erickson, 2009).
retrospective studies that have been reported to date. In a
review of available literature, Lew and associates (2006) re-
ported that 18–22% of PTH lasted longer than 1 year. In an
1Department of Rehabilitation Medicine,2Department of Neurology,3Department of Psychiatry and Behavioral Medicine, and4Department
of Neurological Surgery, University of Washington, Seattle, Washington.
5Craig Hospital, Denver, Colorado.
6Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, Minnesota.
7Department of Physical Medicine and Rehabilitation, University of Alabama at Birmingham, Birmingham, Alabama.
8Department of Neurology, University of Texas Southwestern Medical School, Dallas, Texas.
9Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, Virginia.
10Department of Physical Medicine and Rehabilitation, Moss Rehab, Philadelphia, Pennsylvania.
JOURNAL OF NEUROTRAUMA 28:1–8 (September 2011)
ª Mary Ann Liebert, Inc.
examination of returning service members, Hoge and col-
included a loss of consciousness described having headaches
in the past month. Headache was the only physical symptom
that remained related to mild TBI after controlling for mental
disorders (Hoge et al., 2008). Some studies have reported that
the prevalence of PTH in civilian injuries is higher following
mild TBI than moderate to severe TBI (Couch and Bearss,
2001; Lahz and Bryant, 1996; Uomoto and Esselman, 1993;
Yamaguchi, 1992). Despite its high prevalence and chronicity,
the actual diagnosis of PTH and its impact on functioning
Retrospective and cross-sectional studies, small or biased
samples, and varying definitions of TBI have contributed to
the poor understanding of the natural history of PTH. More
definitive studies characterizing PTH are needed to improve
trials of interventions to facilitate return to normal function in
this population. Previous attempts to characterize PTH have
not included representative samples followed longitudinally,
with attention to possible risk factors for the development of
headache (Baandrup and Jensen, 2004; Bettucci et al., 1998;
Couch and Bearss, 2001; Faux and Sheedy, 2008). In the cur-
rent study we sought to describe the rate of PTH over the first
year following TBI, to compare persons who develop head-
for the development of PTH.
in the study during acute inpatient rehabilitation hospitali-
zation following TBI. Recruitment occurred in tandem with
that of the larger model system database study at 7 TBI Model
Systems (TBIMS) centers between February 2008 and June
2009. Follow-up assessments were completed by July 2010.
Inclusion criteria were the same as for the TBIMS, for which
participants: (1) presented to the designated TBIMS acute care
hospital within 72h of injury; (2) received both acute medical
and acute rehabilitation care within the same system; (3) had
sustained a TBI with at least one of the following character-
istics: Glasgow Coma Scale (GCS) score <13 on emergency
admission (not due to intubation, sedation, or intoxication),
loss of consciousness >30min (not due to sedation or intoxi-
cation), post-traumatic amnesia (PTA) >24h, or trauma-
related intracranial abnormality on neuroimaging; and (4)
were aged 16 years or older. Participants were excluded if
they were incarcerated or did not have telephone access. In-
formed consent was obtained as approved by the institutional
review boards of all 7 institutions. If the subject was unable to
consent due to persistent confusion, proxy consent was ob-
tained from their legally authorized representative.
Initial data were collected on headache and headache
treatment prior to or within 1 week after discharge from in-
patient rehabilitation. Follow-up interviews were conducted
by telephone by trained research assistants using structured
interviews at 3 and 6 months and at 1 year after injury as part
of the planned TBIMS follow-up. Proxy respondents com-
pleted more limited questionnaires when participants were
either cognitively unable to respond validly, or were un-
available during the initial or follow-up interview windows.
Questionnaires completed by proxies occurred with 68 pa-
tients at initial evaluation, 59 at 3 months, 70 at 6 months, and
48 at 12 months post-injury. A comparison of proxy to par-
ticipant responses found no significant difference in report of
headache (versus no headache) pooled over time, but un-
derreporting of headache at 3 and 6 months post-injury by
proxies compared to participants with TBI. Of the 452 en-
rolled patients, follow-up rates were 81% at 3 months, 90% at
6 months, and 88% at 1 year post-injury.
As part of the overarching TBIMS study, basic demo-
graphic data were collected from participants during inpa-
tient rehabilitation, including age at injury, sex, race (white,
black, Asian/Pacific Islander, Native American, Hispanic,
and other), completed high school/did not complete high
school, and cause of injury (moving-vehicle-related, violence,
sports, fall, hit by object, and other). Severity of TBI was ob-
tained using duration of prospectively assessed PTA catego-
rized as mild (0–1 day of PTA), moderate (1–7 days PTA), or
severe (>7 days PTA).
A headache survey included questions about current
headache at initial evaluation during inpatient rehabilitation
(yes/no), history of premorbid headache prior to injury, and
headache at follow-up. In the current study, PTH was defined
as any headache occurring after injury, and did not follow the
ICHD classification limitation based on occurring within the
first 7 days post-injury or regaining consciousness. History of
premorbid headache and follow-up PTH at each time point
and by frequency (less than once per month, once a week to
thepast3months).History ofheadachewasdeterminedby the
question ‘‘How often did you have a moderate to severe
headache before your injury?’’ Prevalence of headache was
calculated using positive endorsement of any headache at
each assessment point divided by the total number of
responders at each assessment. Incidence and cumulative in-
cidence were calculated for total PTH using all possible re-
spondents (n=452), beginning with initial assessment during
inpatientrehabilitation,with incidence showing newcases that
occurred at each follow-up after the initial assessment, and the
cumulative incidence being a sum of all participants who ever
endorsed headache over time. Incidence and cumulative inci-
dence were also calculated based on frequency of headache
(less than one per month, one per week to one per month, and
several times a week to daily) for follow-up assessments (3, 6,
and 12 months). Finally, we also compared those who had no
headache at all follow-ups (3, 6, or 12 months) to those who
either reported headache at all 3 time points, or who reported
headache at some (one or two) time points.
Chi-square analyses were used to compare those with and
without a history of headache, males and females, and TBI
severity across consistency of headache over time.
Demographics of the 452 participants enrolled in the study
are presented in Table 1. The majority of participants were
2 HOFFMAN ET AL.
male, white, had completed high school, and were injured
in vehicle-related incidents. Table 1 also shows that the
prevalence of headache remained consistently high across
the first year after injury. While only 18% of the partici-
pants reported a history of headache prior to injury, more
than 41% of individuals reported headaches at initial evalu-
ation, and at 3, 6, and 12 months post-injury. Infrequent
headaches (fewer than 1 per month) were less prevalent
than frequent headaches (several times per week or daily),
16% compared to 22% at 12 months, respectively. Finally,
of those participants who completed all assessments, the
majority reported headache at one or two time points after
injury, with 23% reporting headache at all three post-injury
Incidence and cumulative incidence of PTH over time
During the first year after TBI, the cumulative incidence of
headache was 71% (Fig. 1). The highest incidence of headache
occurred at baseline, when 44% of participants endorsed
headache. However, while new headache reports decreased
over time, the incidence of new headache remained close to
20% from 3–12 months after injury. Figure 1 also shows the
incidence and cumulative incidence for the subset of partici-
pants who endorsed frequent headaches, or headaches that
occurred several times per week or daily. Eighteen percent of
participants reported frequent headache at 3 months post-
injury, with a total cumulative incidence of 31% over the first
year after injury. In contrast, participants with less frequent
headaches reported incidences of 5% (infrequent headache),
and 13% (between 1 per week and 1 per month), at 3 months
post-injury (data not shown).
Potential risk factors in the development
and maintenance of PTH
Demographic factors including age and sex were examined
as potential risk factors for the development of PTH, along
with prior history of headache before TBI, cause of injury, and
severity of TBI. History of headache and being female were
found to be significantly related to higher rates of headache
over time; 81 of the 452 (18%) participants reported a history
of headache. We compared the population of participants
who reported having a history of headache prior to injury
with those who did not. The results are shown in Figure 2 for
participants with complete data at 3, 6, and 12 months post
injury (n=333). Individuals with a history of headache were
significantly more likely to report headache at all time points
compared to those without a history of headache (45% versus
19%; chi-square=25.1; p<0.001). While the majority of those
with a history of pre-injury headache reported at least one
headache over 1 year, there were 5 participants (9%) with pre-
injury headache who reported no headaches over the entire
first year after injury. For those with a pre-injury headache,
91% continued to report at least one headache over time
compared to those without a history of pre-injury headache
(62%). Though the participants were primarily male (71%),
females were more likely to report any headaches over time
(74% versus 63%), and were much more likely to report
headache at all time points (37%) compared to males (18%;
chi-square=13.5; p<0.01; Fig. 3).
We examined severity of TBI as a determinant of PTH (Fig.
4). The incidence of headache reported across 3, 6, and 12
months post-injury was not significantly different whether
TBI severity was mild (0–1 day), moderate (1–7 days), or se-
vere (>7 days), as determined by length of PTA (77%, 68%,
and 65%, respectively; chi-square=2.3, p=0.67). Examination
in headache over time (data not shown).
The prevalence of PTH wasover 40% at all time points over
the first year after TBI, which suggests that PTH is a frequent
problem that continues long after the initial TBI. In addition,
PTH is a widespread problem, with a cumulative incidence
reaching 71% in this prospectively collected sample of par-
ticipants. This high rate of headache over time has not been
previously reported. Prior research has suggested lower
prevalence rates of headache at 1 year, between 18% and 33%
(van der Naalt et al., 1999; Walker et al., 2005), with only one
study of veterans (who were mostly male), with rates of
headache at 1 year of 40% (Walker et al., 2005).
Table 1. Demographics and Headache Characteristics
n (%) Variable
Completed high school
Cause of injury
Hit by object
Mild (<1 day PTA)
Moderate (1–7 days PTA)
Severe (>8 days PTA)
Overall prevalence of PTH
Inpatient rehabilitation (n=432)
3 Months post-injury (n=362)
6 Months post-injury (n=402)
12 Months post-injury (n=392)
Headache consistency (n=333)a
No headaches at any time
Headaches at all time points
Headaches at intermittent points
a333 participants completed questionnaires at all 3 follow-up time
points (3, 6, and 12 months post-injury).
PTA, post-traumatic amnesia; TBI, traumatic brain injury; PTH,
post-traumatic headache; SD, standard deviation.
HEADACHE AFTER TRAUMATIC BRAIN INJURY3
Our findings show that 28% of new headaches are reported
after the initial evaluation, occurring at 6 and even 12 months-
post injury. The ICHD criteria for a diagnosis of acute or
chronic PTH requires that onset of headache must occur
within 1 week of regaining consciousness after TBI; therefore
the issue of any temporal relationship is important. In-
dividuals with more moderate or severe TBI may not be re-
sponsive or able to verbalize pain due to headache within the
first week after injury (Sherman et al., 2006). Even the authors
of the ICHD diagnostic criteria acknowledge the difficulty in
distinguishing a high general population prevalence tension-
type headache from PTH occurring weeks or months after
trauma (The International Classification of Headache Dis-
and Erickson (2009), who examined the temporal association
population, and found that only 27% of headaches developed
within a week post-trauma. Whether such classification, or
misclassification, of headache after TBI is important is under
debate. In its present form, a diagnosis of PTH does not rely
on symptom criteria or provide direction for treatment.
However, misclassification or missed diagnoses may under-
estimate the true incidence and prevalence of PTH, which
could negatively impact treatment decisions as well as inter-
fere with medico-legal issues in securing financial support for
ongoing management of TBI.
In our sample, rates of PTH were high in all three severity
groups, with no significant differences as a function of length
of PTA. Further studies need to be conducted to confirm this
finding in representative and prospectively studied groups of
participants with a broad range ofTBI severity. Our sampleof
‘‘mild TBI’’ (i.e., PTA less than 1 day) contained only 25 par-
ticipants (6% of the total participants) who were admitted for
inpatient rehabilitation. These participants may be classified
as having complicated mild traumatic brain injuries, as 24 of
the 25 had GCS scores of 13–15, and 23 of the 25 had head CT
n=452). Total HA incidence is the proportion of cases ascertained with HA for the first time after TBI at each time point. The
values underestimate the true incidence because not all participants were assessed at each time point.
Incidence and cumulative incidence of total headache (HA) and frequent HA after traumatic brain injury (TBI;
percentage of participants who reported headache (HA) at 3, 6, and 12 months post-injury. Some time points category
includes reports of HA at one or two, but not all three time points (chi-square=25.1; p<0.001).
Prior history of headache as a determinant of post-traumatic headache (PTH). All time points category includes the
4 HOFFMAN ET AL.
abnormalities (Williams et al., 1990). However, the presence
of CT scan abnormalities would classify these injuries in the
moderate-to-severe category in some classification systems
(Malec et al., 2007), making this sample more homogeneous
and possibly limiting the extent to which differences in PTH
incidence differ betweeninjury severity classes. Priorresearch
that has supported the idea of higher rates of headache in
individuals with mild TBI has often focused on individuals
presenting to outpatient clinics with a wide variation in time
since injury and with varying presenting problems (Couch
and Bearss, 2001; Uomoto and Esselman, 1993). While our
mild group is likely more severely injured than those with
mild TBI referred to in the literature, our rates of PTH with
varying levels of severity of brain injury are similar and high.
Our finding is consistent with the findings of a prior study
which reported on rates of post-traumatic symptoms that
included headache at 1 year in a prospectively studied group
of participants with TBI with a broad range of TBI severity
(Dikmen et al., 2010). Future studies will need to include
similar definitions of TBI severity as well as headache in
representative and non-select cases.
Consistent with prior research, we found that a history of
premorbid headache is significantly related to headache after
TBI. This highlights the importance of assessmentof premorbid
headache as a risk factor for PTH, and may guide treatment
options for physicians caring for individuals with TBI. In
(HA) at 3, 6, and 12 months post-injury. Some time points category includes reports of HA at one or two, but not all three
time points (chi-square=13.5; p<0.01).
Gender as a determinant of post-traumatic headache (PTH). All time points category includes reports of headache
includes reports of headache (HA) at 3, 6, and 12 months post-injury. Some time points category includes reports of HA at
one or two, but not all three time points (chi-square=2.3; p=0.67).
Severity of traumatic brain injury (TBI) as a determinant of post-traumatic headache (PTH). All time points category
HEADACHE AFTER TRAUMATIC BRAIN INJURY5
addition, females were found to have higher rates of headache,
similar to the rates seen in the general headache literature (Jen-
headache at all time points significantly more frequently than
sex characteristics was not assessed, since such data were not
collected. Future research is needed to examine whether these
potential risk factors of sex and history of headache prior to
injury may influence the treatment or diagnosis of PTH.
The current study does have limitations. First, all infor-
mation about headache was collected by trained examiners
using a standardized questionnaire in person (initial assess-
ment), or over the phone (for follow-ups), and there was no
physician evaluation. However, the headache questionnaire
was developed by experts in headache and TBI to include
relevant data similar to that which would be collected in a
physician’s office. Second, only participants who were hos-
pitalized for rehabilitation were eligible for our study; there-
fore the sample may not be entirely representative of patients
with TBI within this severity range in general. However, it is
important to point out that subject selection was not related to
pre- or post-injury headache.
Third,we cannotdetermine theeffectof TBI as compared to
injuries to other body parts with respect to headaches, as we
did not have a non-head-injured trauma control group. Fi-
nally, information about the headaches was collected from
proxies that knew the patient well pre- and post-injury in a
fraction of the cases (15%), either due to the degree of neuro-
availability of the subject at follow-up evaluations. However,
proxies tended to report headache less frequently than par-
underestimation of the likely rates of headache in our sample.
In summary, our data show that PTH is a frequent conse-
quence of TBI and occurs in a much larger percentage of per-
sons than previously reported. We found that 23% of
participants reported headache at all time points over 1 year
after injury, with 22–29% reporting frequent headaches (mul-
tiple times per week/daily). In contrast only 4–5% of persons
1998; Silberstein and Lipton, 1994). Finally, the severity of TBI,
at least within the range represented in our sample, does not
appear to determine the incidence of PTH. We found a similar
rate of PTH across a range of PTA durations.
Future research is needed to determine the clinical char-
acteristics of PTH. Our findings and future findings of clinical
characteristics may have relevance for the development of a
new classification scheme for PTH. Better understanding of
the characteristics and natural history of PTH may provide us
with a framework on which to study early, aggressive treat-
ments to prevent or reduce the frequency of chronic PTH, and
to alleviate suffering.
Dr. Hoffman had full access to all of the data in the study
and takes responsibility for the integrity of the data and the
accuracy of the data analysis.
This study was funded by the Department of Education,
the National Institute on Disability and Rehabilitation
Research (NIDRR), TBI Model Systems: University of Wa-
shington Traumatic Brain Injury Model System H133A070032,
the Rocky MountainRegional
H133A070022, the Mayo Clinic Traumatic Brain Injury Model
System H133A070013, the University of Alabama at Birming-
ham TBI Model System H133A070039, the North Texas Trau-
matic Brain Injury Model system H133A0252604, the Moss
Traumatic Brain Injury Model System H133A070040, and the
Virginia Commonwealth Traumatic Brain Injury Model Sys-
Author Disclosure Statement
Dr. Hoffman, Dr. Lucas, Dr. Dikman, Ms. Braden,
Dr. Brown, Dr. Brunner, Dr. Diaz-Arrastia, Dr. Walker,
Dr. Watanabe, and Dr. Bell receive research funding from the
NIDRR. Dr. Lucas receives funding for other clinical research
from Merck, MAP Pharmaceuticals, Inc., Nupathe, the Na-
tional Headache Foundation, and the Wadsworth Founda-
tion. She also received institutional support for lectures given
to Merck, GlaxoSmithKline, and Zogenix. Dr. Dikmen re-
ceives research funding from the National Institute of Health
(NIH) and the Department of Defense. Dr. Bell receives re-
search funding the Department of Defense. She received
payment for travel and lecture to attend the 3rd Croatian
Congress on NeuroRehabilitation and Restoration Neurology
and for the American Association for the Advancement of
Science, Contemporary Forums. She has received funding for
travel to attend the American Academy of Physical Medicine
and Rehabilitation, INTRuST Clinical Consortium, Alaska
Brain Injury Network, Third Trauma Spectrum Conference,
Brooke Army Medical Center, and the Kaiser Foundation.
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Address correspondence to:
Jeanne M. Hoffman, Ph.D.
Department of Rehabilitation
University of Washington
Seattle, WA 98195-6490
HEADACHE AFTER TRAUMATIC BRAIN INJURY7
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