Posttraumatic Headache Associated with Mild Traumatic Brain Injury

Posttraumatic headache (PTH) can result from traumatic brain injury (TBI), whiplash, or craniotomy. PTH is among the most frequent acute and persistent symptoms following mild TBI (mTBI). Because mTBI is a common occurrence, PTH attributed to mTBI is encountered often in clinical practice. This article focuses on the diagnosis and treatment of PTH attributed to mTBI.

Diagnosis

The diagnosis of PTH attributed to mTBI depends on the timing of PTH onset in relation to having an mTBI. The International Classification of Headache Disorders, 3rd edition (ICHD-3) diagnostic criteria for PTH attributed to mTBI is listed in Table 1.¹ There are no headache characteristics or associated symptoms that are required for a diagnosis of PTH; the presence of PTH onset within 7 days of the TBI is adequate evidence that the headache is attributable to the brain injury. PTH is considered acute when 3 months have not yet passed since its onset, and persistent when PTH has been present for at least 3 months.

Timing of PTH Onset

The ICHD-3 stipulates that PTH develops within 7 days of the TBI, after consciousness returns post-TBI, or after medications that impair the ability to sense or report PTH have been discontinued.¹ For the patient with PTH attributed to mTBI, onset within 7 days of the brain injury is the most relevant criterion. Although most PTH cases start within 7 days of an mTBI, most commonly within the first day, a minority of individuals with PTH have onset after the first 7 days.² It is debatable whether these delayed-onset headaches have similar or different pathophysiology compared with PTH that begins in close temporal relationship to the TBI.

Headache Characteristics and Associated Symptoms

The phenotype of PTH commonly is determined by comparing the similarity of symptoms with those of other primary or secondary headache disorders, such as migraine, tension-type headache, or cervicogenic headache. When people with PTH are seen in clinical settings, PTH symptoms most commonly resemble those of migraine, with headaches associated with a combination of hypersensitivities to visual and auditory stimuli, nausea, cutaneous allodynia, worsening with physical activity, and visual aura.^3,4 At other times, PTH resembles tension-type headache, with mild to moderate nonthrobbing bilateral headaches not associated with sensory hypersensitivities or nausea. If whiplash or other neck injury occurred along with the mTBI, neck pain and neck movement might exacerbate or generate PTH, resembling cervicogenic headache. Less commonly, PTH can resemble a trigeminal autonomic cephalalgia, such as cluster headache.⁵

PTH Persistence

The majority of PTH cases resolve within several days of onset. Approximately one-third of people with acute PTH have persistent headache.^4,6-9 Several possible predictors for PTH persistence have been proposed, including female sex, older age, substance use, history of neurologic disease, history of psychiatric disease, having a primary headache disorder prior to the TBI, number of lifetime TBIs, abnormal brain imaging, extracranial injuries, duration of posttraumatic amnesia, severity of post-TBI symptoms during the acute phase, anxiety and depression symptoms, and lower patient expectations for improvement.^6,10-12

Pre-TBI Headaches

Because primary headache disorders are prevalent in the general population and having a primary headache disorder prior to TBI is a risk factor for developing PTH, it is common for people with PTH to have a history of recurrent headaches prior to the TBI. In this situation, a person is assigned a diagnosis of the pre-TBI headache disorder (eg, migraine) and a diagnosis of PTH, if the headaches worsened or changed substantially within 7 days of the TBI.

Diagnostic Testing

A description of the diagnostic evaluation for TBI is beyond the scope of this article but can be found elsewhere in this issue. For the diagnosis of PTH, it is essential to collect a complete report of the individual’s symptoms and to perform comprehensive neurologic and general physical examinations to determine the likelihood of conditions related to the mTBI that need to be addressed and could be causing PTH. For example, the presence of a prominent orthostatic component to the headache, with headache being significantly more severe when the patient is upright, should raise suspicion for cerebrospinal fluid leak and post-TBI autonomic dysfunction, such as postural orthostatic tachycardia syndrome. People with neck pain and occipital headaches might have cervicogenic headache and require imaging of the cervical spine. People taking pain medications frequently might have developed medication overuse headache. As with primary headaches, frequent use of abortive medications (eg, using nonsteroidal anti-inflammatory drugs (NSAIDs) on 15 or more days per month; using opioids, triptans, or combination analgesics on more than 10 days per month) can cause medication overuse headache and possibly increase the risk for PTH persistence.¹ Other common sequelae of mTBI that might worsen PTH also should be considered, such as sleep abnormalities, oculomotor dysfunction, and increased anxiety and depression.

Treatment

There is a lack of data that can be used to guide the treatment of PTH. Thus, it is common teaching to treat PTH according to the phenotype it most resembles (eg, triptans for PTH that has a migraine-like phenotype; amitriptyline in people with a tension-type phenotype). Until there are data demonstrating efficacy of specific treatments for PTH, it is reasonable to follow this guiding principle.

Pharmacologic and nonpharmacologic treatments for PTH should be considered, as needed.¹³ In addition to abortive medications to treat moderate to severe headaches, preventive medications could be considered.¹⁴ Based on our clinical experience and very limited available evidence, off-label treatment possibilities include triptans or calcitonin gene-related peptide receptor antagonists for acute treatment of PTH with migraine-like phenotype, or NSAIDs or combination analgesics containing acetaminophen for mild or tension-like headaches. From a preventive standpoint, options include several days to a couple of weeks of long-acting NSAIDs, or longer periods using preventive agents such as anticonvulsants (eg, topiramate, pregabalin, gabapentin), antidepressants (eg, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors), calcitonin gene-related peptide receptor antagonists, or onabotulinumtoxinA injections.^14-18

There is preclinical evidence in rodent animal models of PTH that the hyperacute administration of onabotulinumtoxinA and CGRP-targeted monoclonal antibody administration after mTBI fully blocked both acute PTH as well as the transition to persistent PTH, suggesting potential prevention of neural adaptations that promote vulnerability to headache-like pain.^18a,18b The early administration of CGRP monoclonal antibodies also has been shown to prevent the loss of net descending inhibition within central pain modulation pathways, a possible mechanism for persistent PTH.²² The clinical evidence for this is scarce, however. One small, placebo-controlled study in military veterans demonstrated that onabotulinumtoxinA administration resulted in significant improvement in the frequency and pain severity of PTH compared with a placebo.¹⁵ Open label studies with CGRP monoclonal antibodies have reinforced the potential benefit of early treatment for PTH and the potential futility of treating after PTH has become persistent.^18,18c,19 Other small prospective studies of CGRP monoclonal antibodies and onabotulinumtoxinA for the treatment of PTH have reported inconclusive or mixed results.^15,18,19

In addition to typical considerations for prescribing medications, preventive medication recommendations for PTH should consider the likelihood that a medication’s side effects could exacerbate other post-mTBI symptoms, such as topiramate leading to worsening post-TBI cognitive dysfunction or tricyclic antidepressants worsening post-TBI autonomic dysfunction. If there is focal neuralgic pain, blocking extracranial sensory nerves such as the occipital and supraorbital nerves is a reasonable option. Noninvasive neuromodulation could be considered for acute and preventive treatment of PTH.¹⁹ Physical therapy, trigger point injections, massage, and acupuncture can help address musculoskeletal aspects of PTH. Biobehavioral therapies such as cognitive-behavioral therapy and biofeedback also can be useful for PTH treatment.²⁰

The optimal timing for initiating PTH treatment is yet to be elucidated. Within the first few days of PTH onset, avoidance of pharmacologic treatment can be justified if PTH is mild and already improving. In the presence of more severe PTH, medications that abort or lessen headache severity are indicated. The timing for starting preventive medications and nonpharmacologic therapy is less certain. Although existing data about PTH treatment are of low quality, data suggest limited effectiveness of PTH treatment after it has become persistent. These data, along with preclinical data from rodent models of PTH, suggest that earlier intervention might be more effective and may prevent the persistence of headache over time.²¹ However, data are needed from well-designed clinical trials that investigate PTH treatment during the acute and subacute phases to determine whether early intervention is safe and effective for treating symptoms of PTH and preventing its persistence.

Conclusions

In the absence of a diagnostic biomarker, the diagnosis of PTH remains a clinical one. Recent advances have furthered our understanding of the most common PTH clinical presentations and risk factors for PTH persistence. An evidence base for the use of certain treatments for PTH should emerge from ongoing clinical trials evaluating treatments for PTH. Ongoing research also may lead to identification of diagnostic and prognostic biomarkers and an understanding for the role of early prevention to prevent PTH persistence. The existence and pathophysiology of PTH that begins with delayed timing after TBI and the potential role of subconcussive head impacts on the development of PTH are unresolved areas in need of investigation.