Posttraumatic Headache: Basic Mechanisms and Therapeutic Targets

Joshua Kamins, MD; Andrew Charles, MD

Disclosures

Headache. 2018;58(6):811-826. 

In This Article

Characteristics of Posttraumatic Headache – Implications for Pathophysiology

Posttraumatic headache is typically considered broadly as a single entity defined by its occurrence following head/neck trauma. The ICHD does delineate PTH as acute vs chronic, and due to mild vs severe trauma,[5] but there may be substantial additional variability in terms of mechanisms of trauma, clinical features, and course over time. In a significant number of patients, PTH has features of migraine, and patients are commonly categorized by the presence or absence of these features. Classification based on clinical features, however, may not necessarily reflect complexities of pathophysiology, and a better understanding of PTH may require a finer granularity of phenotypic characterization, and the development of specific phenotypic criteria that are distinct from those that have been developed for primary headache disorders.

Mechanisms of Trauma

The nature of the trauma may play a significant role in creating distinct phenotypes with different prognoses. For example, motor vehicle accidents, specific types of sports injuries, and blast injuries may result in distinct patterns of injury with distinct pathophysiological responses. The extent to which the neck is involved in the injury may represent an important contribution to the resulting clinical picture. It has been reported, for example, that among soldiers with mild TBI with (but not without) loss of consciousness, blast injuries were more likely to be associated with persistent headache compared with nonblast mechanisms of injury.[6] Recurrent head/neck trauma may also be associated with a different phenotype of PTH as compared with single traumatic events. Defining categories of trauma mechanisms and whether trauma is a single event or repetitive, may help to better elucidate specific distinct headache mechanisms.

Distribution and Quality of Headache, and Response to Therapy

For migraine, the laterality of headache, whether it is pulsating in quality, its severity, and worsening with activity are defining features.[5] However, migraine pain may be variable from person to person and also from attack to attack in the same individual.[7] Migraine headache is commonly bilateral, it may be constant in quality, and in some cases the pain may be mild or even absent. Posttraumatic headache may be similarly variable in its features. Some previous studies have suggested that posttraumatic headache, particularly in civilians as opposed to military personnel, more commonly has features of tension–type headache.[8–10] However, large prospective studies of PTH consistently find that migraine or probable migraine is the most common classification for PTH in TBI of all severities.[2,11] Ultimately, the goal of classification of PTH is to better understand the disorder and to more effectively manage those who suffer from it. It is possible that even if PTH does not meet the diagnostic criteria for migraine, it nonetheless shares pathophysiological mechanisms of migraine and may respond to migraine–specific therapies (such as triptans). Improved descriptions of the features of the PTH relative to response to migraine–specific therapies could lead to better understanding of shared pathophysiology with primary migraine

Associated Symptoms

The constellation of symptoms occurring with acute concussion are remarkably similar to those of migraine. In addition to headache, the symptoms of nausea, sensory sensitivity, fatigue, difficulty concentrating, dizziness, and irritability are common to the postconcussion syndrome and migraine.[12,13] There may be other associated symptoms that PTH and migraine have in common, but these have not been characterized in detail. For example, premonitory symptoms such as yawning and polyuria, aura symptoms including visual disturbances, paresthesias, and language dysfunction, and postdromal symptoms such as fatigue, and mood change are not as well described in PTH. Clinical experience indicates that even in PTH patients with migrainous features, aura is not a common feature. If true, this is worth noting because it may indicate that cortical spreading depression is not a common mechanism in PTH. Neck pain is another symptom of PTH that is not well described and may have important implications regarding pathophysiology and therapy (see below). As with migraine, dizziness and vertigo may be associated with PTH[14] and may reflect central or peripheral vestibular mechanisms. Benign paroxysmal positional vertigo and other causes of vestibular dysfunction are comorbid with migraine[15] and may also be triggered by head trauma.[14] Shared mechanisms of migraine and PTH involving the vestibular system may represent meaningful therapeutic targets.

Exacerbating Factors

Factors that exacerbate migraine such as stress, hormonal fluctuations, specific medications, and inconsistency of meals, sleep, exercise, and caffeine are widely reported in migraine, but less well characterized in PTH. Stress, and the "letdown" from stress, are commonly reported as migraine triggers, but whether or not these are exacerbating factors for PTH is less well understood. Traumatic brain injury is by its nature a stressful event, so it is reasonable to speculate that the neurochemical and hormonal responses to stress are activated in TBI and could then contribute to headache. The longer term functional and social consequences of TBI (such as lack of ability to participate in work or sports) may also contribute to a stress response that exacerbates headache. While migraine is clearly more prevalent in women and is commonly exacerbated in association with the menstrual cycle, the effects of female sex and sex hormones on posttraumatic headache are less clear. Several studies indicate that female sex does not increase the risk for PTH, but the increased prevalence of preexisting migraine in women may influence the occurrence and clinical features of PTH in women vs men.[11,16] The effect of the menstrual cycle on posttraumatic headache has also not been well characterized.[17] A number of medications may exacerbate migraine, including opioids, butalbital complex, oral contraceptive or hormone replacement therapies, decongestants, selective serotonin uptake inhibitors, and proton pump inhibitors.[18] Little is known about the potential exacerbating effects of these medications on posttraumatic headache. Similarly, nonprescription analgesic use is common in the setting of PTH, and it is unclear whether mechanism involved in the potential exacerbation of headache by medication overuse are the same in the setting of PTH as they are for primary headache.[19]

Positional Exacerbation

Given the potential for changes in CSF dynamics following concussion, it may be worthwhile to characterize whether there is exacerbation of headache with either supine or upright position. It is obviously important to consider intracranial hypotension due to a CSF leak when a postural headache follows trauma, but apart from this secondary headache disorder, it is possible that alterations in CSF pressure could play a role in PTH. Alterations in autonomic function following traumatic brain injury might contribute to postural exacerbation of PTH. In addition to position, breathing patterns may influence CSF flow,[20,21] and breathing exercises could therefore represent a therapeutic approach to PTH. Further, animal evidence suggests that there may be a brain lymphatic system that is involved in clearance of metabolic products.[22] This is a mechanism that could be important in the setting of mild TBI, and therefore PTH.[23] If such a system is indeed important, it could be influenced by position, raising the possibility that alterations in the time spent in the upright vs supine position could be a factor in PTH.

Temporal Characteristics

The temporal characteristics of posttraumatic headache is also important for consideration of underlying mechanisms. It is common for headache to be continuous immediately after concussion, becoming more intermittent over time.[2] On the other hand, in some individuals the headache may remain continuous over an extended period, whereas in others, the onset of posttraumatic headache does not occur immediately with trauma, but emerges after a delay period. As with other primary headache disorders, continuous vs episodic headaches likely represent distinct phenotypes involving distinct mechanisms and requiring specific therapeutic interventions. Similarly, headache that occurs immediately and shows an improving trend in frequency and/or severity over time vs that which remains constant or worsens over time likely represent distinct pathophysiological entities. Phenotypic features or biomarkers that could predict transient vs prolonged headache are desperately needed in order to guide therapeutic decision–making.

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