Posttraumatic Headache: A Comprehensive Approach

Traumatic brain injury (TBI) affects 27 to 69 million people per year worldwide, with the large majority of cases being mild (mTBI). The true incidence of TBI is likely underreported.^1,2 Posttraumatic headache (PTH) is one of the most common and disabling sequelae of TBI; for unclear reasons, PTH appears to be much more common after mTBI than after brain injuries of higher severity.^3,4

Diagnostic criteria for PTH are outlined in the International Classification of Headache Disorders, 3rd edition (ICHD-3).⁵ In part 2 of the ICHD-3, which categorizes secondary headaches, 3 types of PTH are defined: 1) headache after traumatic injury to the head, 2) whiplash, or 3) craniotomy. These types are each divided further into acute (lasting <3 months) or persistent (lasting ≥3 months) subcategories.⁵ The ICHD-3 diagnostic criteria for PTH state that headache should be reported to have developed within 7 days after injury or after regaining consciousness or the ability to sense or report a headache.⁵

The ICHD-3 review committee acknowledged that the 7-day requirement is “somewhat arbitrary,” but requires this temporal relationship between trauma and headache to link them causally. This is potentially problematic, because it implies a causal pathophysiologic link between TBI and headache in all instances when headache follows TBI, even when there may be coincident factors involved outside of the TBI. Therefore, when formulating a diagnosis of PTH, it must be placed into a context of additional elements, such as injury mechanism, concomitant injuries, and surrounding circumstances

ICHD-3 criteria for PTH do not include any clinical characteristics of the headache, such as location, pain quality, or associated symptoms. This information must be obtained from the patient history, as PTH is often treated based on the clinical features and the primary headache disorders with which it most closely aligns (eg, migraine, tension-type headache). This is referred to as the PTH phenotype, but no such defined subclassification system actually exists. The 2 most common phenotypes described are migraine and tension-type, although, because of inconsistencies in study methodology, there is no consensus on which is more common,⁶ and individuals may have characteristics of both.

Finally, to complete the diagnostic picture of PTH, details are needed regarding the chronicity of headache, including frequency and duration, functional impact, and salient physical examination features, which may offer information about coincident pain generators.

Risk Factors for Persistent PTH

Information about the risk factors involved in the development of acute or persistent PTH is sparse.⁷ However, a recent large, prospective, multicenter study of PTH in civilian individuals has added to the body of literature on the topic. In this study, risk factors for acute PTH were identified as history of migraine, previous psychiatric history, positive CT scans, fewer years of formal education, younger age, and female sex.⁸ Risk factors for persistent PTH were a history of migraine, fewer years of formal education, and female sex.⁸ This is consistent with what has been reported previously in several small studies, as collated in a recent review of PTH prevalence, clinical features, risk factors, and treatment strategies.⁹ Another small study¹⁰ identified insomnia, vertigo, and somatic pain as additional risk factors for PTH. However, in contrast to other studies, older age was identified as a risk factor for PTH, and the study authors found that persistent PTH was not correlated with the frequency of psychiatric disorders, highlighting the mixed evidence available.¹⁰ In studies of soldiers, experiencing multiple mTBIs with loss of consciousness¹¹ and the presence of posttraumatic stress disorder (PTSD)¹² were both identified as risk factors for the development of PTH.

Although many of the risk factors that have been identified for the development of persistent PTH are not easily modifiable through intervention, it is valuable to note them, as their presence could indicate that an individual is at a higher risk for progressing from acute to persistent PTH. Additionally, some of the risk factors, such as co-occurring psychiatric disorders, insomnia, vertigo, and somatic pain, can be managed concurrently with acute PTH if identified appropriately and may be effective in decreasing the severity or frequency of an individual’s headaches. It is therefore imperative to screen for the presence of risk factors when interviewing an individual with PTH, with a particular focus on poor-quality sleep, preexisting mood disorders, medication overuse, new PTH-related comorbidities, previous personal or family history of migraine, and high-risk occupational exposures, such as military service with blast exposure or being a first responder (eg, fire, rescue, police, Special Weapons and Tactics [SWAT] team).

Pharmacologic Management of PTH

No drugs have been approved by the US Food and Drug Administration (FDA) for the treatment of PTH, and all pharmacologic management of PTH is considered off-label. Some studies have examined various abortive and preventive migraine and tension-type headache medications for the treatment of PTH, but a high-quality, meaningful evidence base for treatment is lacking.¹³ A recent study of 100 individuals with persistent PTH found that 87% were dissatisfied with their treatment status, with 79% of the 63 participants who had tried preventatives reporting failure of at least 1, and 19% reporting failure of at least 4.¹⁴ A total of 55 out of those 63 individuals remained on the preventative treatments, although they were mostly ineffective. In this same study, 98 out of 100 participants reported abortive medication use, with triptans being the most popular, but 19 of the 39 participants reporting the use of triptans endorsed lack of efficacy.

In the absence of high-quality evidence, a phenotype-guided treatment algorithm based on the available evidence and expert opinion has been proposed.¹⁵ This algorithm proposes NSAIDs as a first-line acute treatment for both tension-type and migraine PTH phenotypes followed by aspirin-paracetamol-caffeine (for both phenotypes) or a triptan for migraine phenotype. For individuals needing prophylactic treatment, amitriptyline, mirtazapine, or venlafaxine were recommended for the tension-type phenotype, and atenolol, bisoprolol, candesartan, metoprolol, propranolol, or amitriptyline for the migraine phenotype.¹⁵ The authors acknowledged that there may be a role for onabotulinumtoxinA and calcitonin gene-related peptide (CGRP) antagonists as treatment options, but anticipated that these may be restricted because of limited access and cost.

Apart from the PTH phenotype, many individuals with PTH have coexisting primary headache disorders, such as migraine. The ICHD-3 stipulates that “when a preexisting primary headache becomes chronic in close temporal relation to such a causative disorder, both the primary and the secondary diagnoses should be given. When a preexisting primary headache is made significantly worse (usually meaning a twofold or greater increase in frequency and/or severity) in close temporal relation to such a causative disorder, both the primary and the secondary headache diagnoses should be given, provided that there is good evidence that the disorder can cause headache.”⁵ For example, an individual with preinjury headaches consistent with episodic migraine who experiences PTH along with migraine phenotype would be diagnosed with migraine as well as PTH, and migraine-specific treatments such as onabotulinumtoxinA or CGRP-modulating drugs would be appropriate.

When selecting a medication to trial, the larger context of comorbid concussion symptoms, concurrent injuries, medical and psychosocial history, and individual preferences must be considered (Figure). An individual with coexisting sleep difficulty may benefit from amitriptyline, whereas an individual with coexisting anxiety or depression may benefit from venlafaxine or another antidepressant. Similarly, individuals with hypertension may be on existing antihypertensive medications that can be changed to medications with dual functions of managing blood pressure and headache prophylaxis.

Another important consideration in the treatment of PTH is the co-occurrence of medication overuse headache (MOH). According to the ICHD-3, MOH is a headache occurring on 15 or more days per month in a person with preexisting headache, developing because of regular overuse of acute headache medication (ie, ≥10 days/month for triptans or ergots and ≥15 days/month for over-the-counter analgesics) for >3 months.¹⁶ It has been suggested that a significant proportion of persistent PTH is caused by MOH, but even when medication overuse is present, stopping the medication does not always yield improvement.¹⁷ We recommend investigating the possibility of MOH and addressing it whenever present as a first step in formulating a PTH treatment plan (Figure).

Nonpharmacologic Management of PTH

PTH does not exist in a vacuum. By definition, PTH follows trauma to the head or neck, so an individual who presents with PTH may also be experiencing co-occurring symptoms of concussion (eg, balance problems, dizziness, fatigue, sleep disturbance, noise or light sensitivity, visual changes, mood dysregulation, autonomic dysfunction),¹⁸ posttraumatic vestibulo-ocular disorder, or posttraumatic cervicogenic disorder.^19,20 Posttraumatic vestibulo-ocular and cervicogenic disorders, as well as mood disorders, can trigger headaches,²¹ complicating the management of PTH.

Given this complexity, it is useful to conceptualize PTH within the larger context of concussion, persistent postconcussive symptoms (PPCS), and potential comorbidities (Figure). We can therefore look to concussion management for guidance on the nonpharmacologic management of PTH. As with any condition, the initial concussion assessment should include a complete history and a focused physical examination. Concussion symptom checklists, such as the Postconcussion Symptom Scale,^20,22 can be used to screen for symptoms of concussion quickly and easily. These individual-reported symptom scales can help identify which symptoms are of the highest priority to the individual. In addition, concussion symptom checklists can be used to identify the predominant symptoms and categorize concussion and PPCS into clinical profiles (eg, autonomic/physiologic concussion/PPCS, vestibulo-ocular posttraumatic disorder, cervicogenic posttraumatic disorder, mood-related PPCS), which can help guide treatment.^19,20 In addition to concussion symptom checklists, a cognitive and behavioral screen can help identify mood or cognitive predominance of PPCS.¹⁹ Poor-quality sleep, anxiety, and depression are more common in individuals with persistent PTH compared with age- and sex-matched healthy controls.²³ There is also substantial overlap among PTH, PPCS, PTSD, and MOH.¹⁸ PTSD is often identified in military personnel, but can also occur in civilian individuals who have experienced a traumatic event. For individuals who have predominant mood-related symptoms on history, or who are reporting exacerbation of preexisting mood disorders, neuropsychologic assessment and treatment or referral to a behavioral health specialist should be considered.

A concussion-specific physical examination should include an examination of the oculomotor, vestibular, and craniocervical systems, in addition to an examination for trigger points or tender points in the distribution of the occipital and trigeminal nerves. In individuals with findings indicative of cervical dysfunction, such as cervical muscle tenderness or spasm, referral for physical therapy should be initiated as soon as possible.¹⁹ Receptors in the neck and suboccipital region provide feedback to the visual, vestibular, and central nervous systems;²⁴ therefore, unaddressed cervical dysfunction can prolong, amplify, or mimic symptoms of concussion and PTH, such as headache, dizziness, blurred vision, and impaired balance. Posttraumatic oculomotor and vestibular dysfunction, as indicated by findings such as abnormal smooth pursuits, repetitive saccades, abnormal vestibulo-ocular reflex, or impaired convergence, may resolve on its own. However, if these findings and associated symptoms (eg, double vision, blurred vision, dizziness, balance difficulties, vertigo) are present for more than 3 to 4 weeks, focused rehabilitation therapy (eg, vestibular physical therapy, vision therapy) should be strongly considered.¹⁹ In cases where cervical dysfunction is identified, it should be addressed before vestibular and oculomotor dysfunction, as individuals with unaddressed cervical dysfunction may not be able to tolerate the maneuvers involved in vestibular and vision therapy because of exacerbation of symptoms.¹⁹

There is limited evidence regarding the nonpharmacologic management of PTH exclusive of PPCS. Two recent systematic reviews explored several nonpharmacologic interventions, summarizing promising findings in studies using neuromodulation, acupuncture, therapeutic exercise or physical activity, cognitive behavioral modification, lifestyle modification, nutraceuticals, interdisciplinary or multidisciplinary rehabilitation, and the application of prism for treatment of PTH.^18,25 The largest volume of evidence was for interdisciplinary or multidisciplinary rehabilitation, cognitive behavioral intervention, and physical activity or therapeutic exercise; however, all studies cited demonstrated positive effects of the tested interventions on PTH.^18,25 The studies included in both reviews were limited by small populations, heterogeneous outcomes, and suboptimal control group or blinding,^18,25 so more research is needed. Lee et al²⁵ advised that nonpharmacologic treatment of PTH be a shared decision between the individual and the clinician, with interventions prioritized in order of ease of implementation. In particular, the authors recommended in consultation with a healthcare provider, nutraceuticals (eg, magnesium, vitamin D, riboflavin, coenzyme Q, melatonin, omega-3 fatty acids) and lifestyle modifications (eg, sleep hygiene and physical activity) as part of first-line nonpharmacologic treatment of PTH given the accessibility of nutraceuticals through dietary supplements and foods and the ease of incorporation of sleep hygiene and physical activity into an individual’s routine without additional oversight.²⁵

Conclusion

PTH may resemble primary headache phenotypes, but it is a distinct entity, further complicated by co-occurring PPCS and additional comorbidities that can increase the risk for persistent PTH, or prolong, amplify, or trigger headaches. Treatment of PTH should be a shared decision between the individual and the clinician. No FDA-approved drug exists for the treatment of PTH, and pharmacologic management of PTH lacks high-quality evidence. Nonpharmacologic treatment should be multimodal, prioritizing the treatment of the associated PPCS that are of most importance to the individual, while accounting for comorbidities and biopsychosocial factors.