Short Research Report

Journal of Concussion
Volume 3: 1–4
Treatment of posttraumatic headache ! The Author(s) 2019
Article reuse guidelines:
migraine phenotype with erenumab – sagepub.com/journals-permissions
DOI: 10.1177/2059700219878292
An observational study journals.sagepub.com/home/ccn

James A Charles

Abstract
Objective: To report the observed effect of erenumab in mild posttraumatic headache migraine phenotype with and
without aura.
Background: There is no clinical algorithm of pharmacotherapy for migraine following posttraumatic headache. Most
migraine preventatives that are typically used are either ineffective or not tolerated.
Methods: Seven patients who met the clinical criteria for migraine with or without aura following posttraumatic
headache who failed or were intolerant of conventional migraine preventatives were treated with erenumab 140 mg
subcutaneously. Most had no history of migraine. In those patients with a history of migraine, the posttraumatic
headache migraine headaches were different than the past migraine experience. Descriptive headache intensity or
disability using the Head Impact Test-6 and monthly headache days were recorded before and after treatment. All
patients were debilitated on presentation and demonstrated no signs of spontaneous resolution.
Results: Patients responded with a 95% (SD 1.22, p < .001) reduction in headache days. All Head Impact Test-6 scores
went from disabling to non-disabling without adverse effects. Most required only one dose of erenumab with no
migraine recurrence. Onset of efficacy often became apparent within days to four weeks. Extended follow-up six
months after treatment revealed no relapses.
Conclusions: Erenumab is effective in the treatment of posttraumatic headache with migraine phenotype in this small
cohort. Large-scale studies are urgently required for this highly prevalent, disabling, condition which has no effective
established treatment.

Keywords
Migraine, posttraumatic headache, concussion, CGRP-R, migraine preventatives
Date received: 14 June 2019; accepted: 27 August 2019

Introduction these patients are treated with preventatives used in

The prevalence of posttraumatic headache (PTH) is non-traumatic migraine patients, but the response is
approximately three million of which 20% are adoles- usually inadequate.
cence.1 Most patients who present with PTH will Erenumab is a CRRP-receptor monoclonal anti-
manifest migraine phenotype which has all the charac- body which is Food and Drug Administration (FDA)
teristics of migraine with and without aura.2,3 All approved for the preventative treatment of migraine. It
patients represented in this observational study fell has an excellent safety profile, impressive efficacy data,
under the International Classification of Headache
Disorders-vs 3 (ICHD3) classification as acute head-
ache attributed to mild traumatic injury to the head Holy Name Medical Center, Teaneck, USA
5.1.2.4 The PTH phenotype was migraine: typical fea-
Corresponding author:
tures include throbbing pounding headache, photopho- James A Charles, Holy Name Medical Center, 718 Teaneck Rd, Teaneck,
bia, nausea, vomiting, visual aura, brainstem aura, and NJ 07666-4245, USA.
inability to engage socially, in school, or work. Most of Email: jacharlesmd@gmail.com
Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-
NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and
distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.
sagepub.com/en-us/nam/open-access-at-sage).
2 Journal of Concussion

can be effective as quickly as one week, and has virtu-
ally no adverse effects except for very low incidence of
injection site reactions and constipation. Erenumab
was the first of the three current FDA approved
CGRP monoclonal antibodies. It is the only antibody
targeting the CGRP receptor. Of the three FDA
approved CGRP monoclonal antibodies, erenumab
has the longest (3 yr) open label extension data.5 Six
patients were treated with erenumab with clinical
migraine phenotype following PTH.
Methods
All patients met the criteria for migraine with or with-
out aura as delineated in ICHD3. The etiology of their
migraines was head trauma which was defined as PTH
secondary to mild traumatic injury to the head. All
patients had normal exams and head imaging. Three
patients had a remote history of migraine six months or
longer with symptoms that differed from the PTH-
induced migraine phenotype and their history of
migraine. General informed consent was obtained
from all patients. Erenumab is FDA approved for the
preventative treatment of migraine with and without
aura. An AHS publication recently recommended
using CGRP mAbs in the pediatric population where
other preventives have failed or not tolerated.6 All
patients failed prior treatments and were disabled
from migraine with intense high-frequency headache,
and inability to work, attend school, or engage in
social circles. Ineffective preventative treatments given
for at least four weeks alone or in combination which
were discontinued with erenumab administration
included daily topiramate, amitriptyline, gabapentin,
doxepin, venlaxafine, memantine, ibuprofen, naproxen,
and ondesterone. Abortives such as non-steroidal anti-
inflammatory drugs (NSAIDS) triptans, or over the
counter non prescription (OTC) analgesics were
allowed but were never taken daily and their need
tapered off quickly with the rapid response to erenu-
mab. The patients were relatively healthy and con-
founding variables such as non-morbid obesity and
concurrent minor illnesses were not significant to be
considered in the outcome analysis. No patient had
medication overuse headache syndrome, pregnancy,
secondary gain motivation, or psychiatric disorders.
Baseline monthly headache days (MHDs) and Head
Impact Test-6 (HIT-6) were recorded and restated
two months after receiving erenumab 140 mg. Only
one patient (patient 5) required a second dose, and
the MHD and HIT-6 were recorded two months after
the second dose. Doses were administered in the office
by a certified medical assistant. Data were assessed
retrospectively.
Results
Patients experienced a 95% (SD 1.22, p < .001) reduc-
tion of MHDs in two months, with headache remission
often commencing within a week of treatment. Prior to
treatment with erenumab, all six patients had HIT-6
scores above 60 indicating severe disability. Two
months posttreatment, all HIT-6 scores fell below
49 which is no disability. Patients were very satisfied
with the reduction of headache, photophobia, nausea,
and dizziness. All patients returned to normal activities
of daily living, work, and school activities. Following
discharge from treatment, patients required either no
abortives or rare use of OTC analgesics. Those patients
with a history of migraine had no difference in response
to erenumab. There were no adverse effects reported.
There were no relapses. Findings are summarized in
Table 1.

Table 1. Table of Pre and Post Treatment Data.

Patient Onset to Rxa MHDs preRX MHDs postRxb HIT-6 preRx HIT-6 postRxc Repeat dosed

1. 41 Fe 4 weeks 30 1 72 42 No
2. 18 Fe 4 weeks 30 1 62 36 No
3. 29 Fe 5 weeks 30 0 74 42 No
4. 15 M 4 weeks 30 0 64 36 No
5. 29 F 5 weeks 20 1 72 38 Yes
6. 29 M 11 weeks 30 2 69 36 No
7. 48 F 6 weeks 30 0 72 36 No
MHD: monthly headache days; HIT-6: Head Impact Test-6.
a
Onset of posttraumatic migraine to first erenumab 140 mg treatment ¼ baseline period. All patients developed headache on day 1 of trauma.
b
MHD after three months after erenumab 140 mg except for patient 5 MHD recorded after second dose of erenumab given at three months following
first dose of erenumab and MHD recorded one month after second dose or four months after first dose.
c
HIT-6 posttreatment at three months, except patient 5 HIT-6 recorded one month after second dose or four months after first dose.
d
Repeat dose of erenumab 140 mg given four weeks after first dose.
e
History of migraine.
Charles
Discussion
These seven patients were severely symptomatic from
migraine that followed mild posttraumatic head injury.
Each patient went from severe disability to no head-
ache disability and 95% reduction of MHDs with the
reduction often commencing within a few weeks
of receiving erenumab 140 mg. There were no
adverse effects.
The real impact of erenumab on these patients was
striking. Patient 6 was a 29 y/o laborer who fell off a
truck, hit head, and experienced daily migraine with no
history of migraine. For 11 weeks he could not return
to work and was unresponsive to vestibular therapy,
topiramate, amitriptyline, gabapentin, and non-daily
triptan and NSAID abortives. Three weeks after one
dose of erenumab, he went back to work with rare
headaches. Patient 4 was a 15 y/o male student wrestler
who was thrown to the floor during wrestling with head
trauma, had daily migraines and could not attend
school due to severe pounding headaches and photo-
phobia worsened with academic engagement. Within
five days of erenumab, he was asymptomatic and
back to his academic classes.
There are no FDA approved treatments for PTH
with migraine phenotype. Studies have shown that con-
ventional treatment of PTH migraine phenotype results
in 26% relief and 74% no relief.7,8 Differences in
regional volumes, cortical thickness, surface area, and
curvature were noted comparing PTH migraine pheno-
type to migraine patients using functional magnetic
resonance imaging.9 However, CGRP receptors are
ubiquitous in the cortex of the entire brain.10 The tri-
geminal vascular access of CGRP-R mAbs via the
meninges may explain the robust response of these
patients to erenumab. Perhaps there is amplification
of the trigeminovascular system in PTH migraine phe-
notype which would account for the failure of conven-
tional migraine preventatives which do not directly
antagonize CGRP receptors which is the mechanism
of action of erenumab. The presence of pre- and post-
synaptic receptors can explain the efficacy of CGRP-
mAbs. In a rat model of concussion, headache and
pain-related behaviors were mediated through a
CGRP-dependent mechanism. Concussed rats’ tactile
pain and hypersensitivity were inhibited by anti-
CGRP antibody treatment.11
Conclusions
This is a small observational study on the effect of
erenumab on patients with PTH-migraine phenotype
with no control group. A placebo effect cannot be
excluded, and the original studies that led to FDA
approval of erenumab for episodic and chronic
3
migraine demonstrated efficacy with a placebo effect
of approximately 30%. None of these patients had psy-
chiatric or secondary gain issues, or currently active
preexistent migraine. Many had failed previous
migraine preventatives. The efficacy and safety of ere-
numab 140 mg in the virtual elimination of migraine
was extremely impressive with no adverse effects.
Concussion with PTH migraine phenotype is a public
health problem. This pilot observation study should
lead to larger studies to validate these findings and
determine if erenumab, which is safe and effective,
should be in the forefront for the treatment of PTH
with migraine phenotype.
Author’s contribution
JAC: Had full access to all the data in the study, integrity of
the data and the accuracy of the data analysis; study concept
and design; analysis; interpretation of data; drafting of the
manuscript; critical revision of the manuscript for important
intellectual content; statistical analysis; technical or material
support; study supervision. JAC is the speaker for Supernus
and Amgen.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of
this article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
ORCID iD
James A Charles https://orcid.org/0000-0001-5485-830X
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