Persistent post-traumatic headache: a migrainous loop or not? The clinical evidence

DOI: https://doi.org/10.1186/s10194- 020- 01122- 5

Abstract-Summary Acute post-traumatic headache resolves after 3 months, but persistent post- traumatic headache usually lasts much longer and accounts for 4% of all secondary headache disorders.

The clinical features of post-traumatic headache after traumatic brain injury resemble various types of primary headaches and the most frequent are migraine- like or tension-type-like phenotypes.

The neuroimaging studies that have compared persistent post-traumatic head- ache and migraine found different structural and functional brain changes, although migraine and post-traumatic headache may be clinically similar.

Therapy of various clinical phenotypes of post-traumatic headache almost entirely mirrors the therapy of the corresponding primary headache and are cur- rently based on expert opinion rather than scientific evidence.

There are also effective options for non-pharmacologic therapy of post-traumatic headache, including cognitive-behavioral approaches, onabotulinum toxin injec- tions, life-style considerations, etc. Notwithstanding some phenotypic similarities, persistent post-traumatic headache after traumatic brain injury, is considered a sepa- rate phenomenon from migraine but available data is inconclusive.

Background Acute PTH is defined when the headache resolves within 3 months after TBI, whereas persistent PTH is characterized by headache lasting longer than 3 months.

In a large cohort during the first year after TBI, the incidence of new-onset head- ache was 44% and the cumulative incidence of headache at 12 months was 71%, with a 20% incidence of persistent PTH [30].

Migraine patients who developed PTH have a twofold increase in the frequency and/or intensity of the headache after the injury [6, 30], whereas PTH patients with pre-existing tension-type headache also experience a slight increase in attack fre- quency [1, 34].

The severity of headache, recovery time, race, marital status, level of education, alcohol use at the time of injury, the etiology of TBI and Glasgow Coma Scale scores are not risk factors for the development of persistent PTH [31, 35, 36].

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The aim of this review is to discuss if there is a migrainous loop for persistent PTH and to provide a better understanding of the underlying mechanisms of migraine and headache attributed to TBI according to current evidence.

Clinical Presentation In one study, for instance, tension-type-like headache was reported in 97% of patients with de novo headache after mild TBI and persistent PTH [20].

A migraine-like headache or a probable migraine-like headache was described in

49% of patients with persistent PTH after mild TBI [1].

Patients with migraine-like PTH are more likely to have headache several days a week or daily [34]; these patients have a higher probability to have migraine 1 year after injury [1].

Several studies have reported that individuals with persistent PTH develop migrainous features, including the throbbing headache, unilateral location, pain exacerbation by physical activities, moderate to severe pain, headache accompanied by nausea or vomiting, and photophobia and/or phonophobia [37–41].

Different inclusion criteria for (persistent) PTH have been established in some studies, potentially weakening evidence of causation—for example longer interval between trauma and headache development [19, 20].

Neuroimaging Studies A study conducted by Obermann and others in 32 patients with whiplash injury without pre-existing headaches, found that patients who developed persistent PTH, compared to healthy controls and patients affected by acute PTH, showed a decreased anterior cingulate and dorsolateral prefrontal cortex (DLPFC) gray mat- ter density, areas of the default mode and salience network [42].

Schwedt and others compared measures of brain regional volumes, cortical thickness, surface area and brain curvature amongst 28: migraine patients, individu- als with persistent PTH following a TBI without history of pre-existing headaches and healthy controls [26].

This study demonstrates that persistent PTH patients have different static and dynamic functional connectivity compared with migraine patients for regions involved in pain processing.

Alhilali and others compared DTI studies of 58 patients with acute or persistent PTH of a migraine phenotype with unknown pre-existing headache history, with 17 patients with mild TBI without headache [25].

Neurophysiological Studies A more recent study on patients with mild or minor closed head injuries, selected on the basis of of lack of unconsciousness on admission and normal neurological examinations, revealed 54% with focal and diffuse slowing EEG abnormalities [43]. Brain-stem auditory evoked potentials have been found to be abnormal in 10–20% of patients with head injury and post-concussion syndrome, more fre- quently in those with prolonged unconsciousness [44].

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Post-concussion Syndrome

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Most of the researchers who recorded short-latency brainstem auditory evoked potentials were not able to find any interictal abnormalities in migraine, probably because they pooled patients with different migraine phenotypes (MO and MA or different MA subtypes) in different proportions in a single group [45].

One study demonstrated significant abnormalities of P300 amplitude and latency

in 20 head injury patients compared with 20 control subjects [46].

Electronystagmogram is abnormal in 40–50% of patients with head injury or

“whiplash” in clinic-based studies.

Treatment There is no available data from randomized controlled trials evaluating the thera- peutic efficacy of medical interventions specific to persistent PTH, therefore, the therapy mirrors conventional treatment approaches for non-traumatic primary head- ache disorders [47].

There is only one observational clinical study completed, evaluating the treat- ment of PTH appearing as migraine phenotype with erenumab in 7 patients, which showed exceptional efficacy of 140 mg erenumab measured in reduction of head- ache days and Head Impact Test-6 [48].

This pilot study demonstrates an overall time effect on headache severity, func- tional impact, depression, PPCS, and quality of life following rTMS treatment in participants with persistent PTH, however, findings were below clinical significance thresholds.

Current proper management of persistent PTH requires recognition of the pri- mary headache type resembling by persistent PTH and tailoring pharmacologic and non-pharmacologic treatments to the individual patient.

Conclusions Persistent PTH is a disabling sequela with unknown pathophysiology and lack of specific treatments.

These disorders share some phenotypic similarities, furthermore, the history of migraine is a risk factor for developing persistent PTH and migraine treatment is reported to be efficient in PTH patients.

Despite some phenotypic similarities persistent PTH seems a distinct entity and high-quality studies are further required to investigate the pathophysiologic mecha- nisms of this secondary headache, in order to develop new targets for treatment and to prevent disability.

Acknowledgement A machine generated summary based on the work of Labastida-Ramírez, Alejandro; Benemei, Silvia; Albanese, Maria; D’Amico, Antonina; Grillo, Giovanni; Grosu, Oxana; Ertem, Devrimsel Harika; Mecklenburg, Jasper; Fedorova, Elena Petrovna; Řehulka, Pavel; di Cola, Francesca Schiano; Lopez, Javier Trigo; Vashchenko, Nina; MaassenVanDenBrink, Antoinette; Martelletti, Paolo; 2020 in The Journal of Headache and Pain.

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Post-traumatic Stress Disorder After Traumatic Brain Injury—A Systematic Review and Meta-Analysis