Y. W. 2020 in The Journal of Headache and Pain.

Imaging Post-Traumatic Headache

DOI: https://doi.org/10.1007/s11916- 018- 0719- z

Abstract-Summary The goal of this review is to summarize findings from imaging studies used during the clinical evaluation and research investigation of post-traumatic headache (PTH). Several guidelines for when to image the patient with mild traumatic brain injury

(mTBI) in the emergency setting consider headache among the deciding factors.

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In the research arena, imaging techniques including proton spectroscopy mag- netic resonance imaging, diffusion tensor imaging, magnetic resonance morphom- etry, and functional neck x-rays have been employed with the goal of identifying diagnostic and prognostic factors for PTH and to help understand its underlying pathophysiologic mechanisms.

Future research should interrogate whether these imaging findings contribute to

the classification and prognosis of PTH.

Current research provides evidence that imaging findings associated with PTH

may be distinct from those attributable to mTBI.

A variety of imaging techniques have potential to further our understanding of the pathophysiologic processes underlying PTH as well as to provide diagnostic and prognostic indicators.

Extended: In the research arena, the studies using imaging to investigate PTH

signify progress toward our understanding of PTH.

Introduction The most frequently occurring symptom of mTBI, reported in up to 90% of patients, is headache [91, 118].

Individuals experiencing mTBI more frequently report having headaches than

patients with moderate or severe TBI [1, 19, 30, 61, 79–118].

Headache is a poor prognostic factor; patients who report headache as a symp- tom of mTBI in the acute setting have a longer recovery periods [91, 92, 119, 120] and are more likely to have persistent post-concussion symptoms at 1 and 3 months [91, 121–124].

Between 50 and 80% of individuals with whiplash injury report headache as a

symptom [125, 126].

Like headaches attributed to mTBI, headaches that occur after whiplash injury typically resolve within several weeks to a month, but persistent headaches have been shown in over 30% of patients at 1 and 3 months and 15% at 1 year [125].

Patients with PTH of a migraine phenotype (PTH-MP) have a greater risk of prolonged symptom recovery than individuals with other PTH phenotypes or mTBI without headache [91, 92].

Clinical Imaging of PTH Imaging of the head and brain after mTBI is not always indicated, but when per- formed, assesses for cranial lesions that can be associated with “complicated mTBI,” moderate, and severe TBI.

Rules and clinical policies for when head CT is needed to evaluate the patient

with suspected mTBI are available [127–129].

The presence of headache in the patient with mTBI who also has loss of con- sciousness or amnesia suggests the need for acute imaging within the New Orleans Criteria [130], and headache is a symptom that contributes to the decision for CT imaging in the clinical policy from the American College of Emergency Physicians and Centers for Disease Control and Prevention [131].

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The guidelines for CT imaging for mTBI may be re-evaluated in the near future because of the recent FDA approval of a blood test that predicts with over 99% accuracy whether or not there is intracranial bleeding after a TBI [132–134].

Research Imaging of PTH In the research arena, several imaging techniques have been used to further our understanding of mTBI by examining changes in structure, function, connectivity, and brain metabolism [135–138].

We discuss the current research imaging literature in PTH following mTBI.

Proton Spectroscopy Magnetic Resonance Imaging: Interrogating Brain Metabolism Sarmento and others [58] examined the levels of N-acetylaspartate (NAA), a marker of neuronal vitality, as well as choline (Cho) levels which represent neuronal cell membrane turnover using 1H-MRS.

Nine regions were analyzed (left and right anterolateral and posterolateral fron- tal, lobes, anteromedial and posteromedial frontal lobe, left and right lateral parietal lobes, and medial parietal lobe).

The investigators found a significant reduction in NAA in PTH subjects com- pared with controls in the right and left anterolateral frontal lobe white matter, ante- rior and posterior medial frontal lobes, and medial parietal lobes.

Increased Cho was found in the right posterolateral frontal lobe white matter and

the anterior medial frontal and medial parietal regions.

The authors concluded that NAA decreases were representative of axon morpho- logic changes occurring in the white matter and that increased Cho levels indicated cell membrane turnover and hence healing.

Diffusion Tensor Imaging: Interrogating White Matter Integrity In a retrospective analysis, Alhilali and others [7] compared FA in 58 subjects with PTH-MP to 17 controls with mTBI (control subjects could have PTH without migraine phenotype).

The technique uses whole-brain histograms of FA and calculates a single value, Shannon entropy (SE), which is a measure of data complexity that was developed in the field of information theory.

In the Delic and others study, the investigators use retrospectively collected data to calculate the SE and mean FA of the whole-brain histograms of FA in patients with mTBI without PTH-MP (n  =  17), PTH-MP (m  =  57), migraine but no TBI (n = 20), and healthy controls (n = 22).

It was determined that an SE value of less than 0.751 could discriminate between subjects with mTBI and controls with 77% sensitivity (95% CI, 65, 86) and 95% specificity (95% CI, 74, 100) with a likelihood ratio of 16.1 (95% CI, 2.4, 109.7).

MRI: Advanced Measures of Brain Structure Using the initial scan, voxel-based regional brain densities were compared between patients with acute PTH (n = 20), those who developed persistent post-traumatic headache (PPTH) (n = 12) and sex-matched and age-matched healthy controls with- out headache or brain or neck trauma (n = 30).

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Cortical thickness was not greater in PPTH patients compared to controls in any

brain region.

Schwedt and others [139] calculated regional brain volumes, surface areas, corti- cal thicknesses, and curvatures in individuals who had PPTH (n  =  28), migraine without a history of TBI (n = 28), and healthy controls (n = 28).

When these same regions in PPTH subjects were compared to healthy controls, only three of the structural variations were evident. (PPTH had smaller right lateral orbitofrontal surface area, smaller right supramarginal gyrus thickness, and smaller left superior frontal thickness.) There were no differences between migraine and healthy controls in any of the seven regions found to be different between migraine and PPTH patients.

Imaging the Neck in PPTH Jensen and others [140] measured segmental and overall extension-flexion motion of the cervical spine using flexion/extension x-rays in 19 patients with PPTH and 19 age-matched and sex-matched healthy controls.

The investigators found a significant 10% reduction in overall C1–C7 extension-

flexion motion in patients with PTH compared to controls.

Headache severity was negatively correlated with age-corrected C1–C7 motion

in patients with PTH.

Reduced overall cervical motion in PPTH patients may represent reduction of motion due to head and/or neck pain, or it may have a different physiologic explanation.

Discussion Three of the above studies compared PTH with a healthy control group [57, 58, 140] and so, the differences detected may reflect brain injury rather than mechanisms related to headache.

Even when comparisons were made between patients with mTBI with and with- out headache, it is unlikely that PTH was the only post-concussive symptom being experienced.

While studies that compare PTH to mTBI may be examining pathology specific

to headache, alternatively, results could be reflective of total symptom burden.

In studies comparing PTH-MP to mTBI patients without headaches of migraine phenotype [7], results may indicate the underlying differences in pathophysiology relating to the migrainous nature of the headache.

Alhilali and others [7] did demonstrate reduced integrity of the white matter of the corpus callosum and fornix/septohippocampal circuit in PTH-MP compared to the mTBI group.

Conclusions Imaging techniques that have been applied to headache [137, 141–144] or mTBI [135, 138, 145] with some success and that have not yet yielded publications in PTH include fMRI, PET, and SPECT (with phosphorous—31P MRS) and arterial spin labeling.

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While it is recognizably difficult to achieve, ideal studies will compare mTBI with persistent symptoms not including headache to PTH attributed to mTBI, or PTH to primary headache types, controlling for other post-concussive symptoms.

Imaging would assist with prognosticating PTH outcomes, assist with identifica- tion of individuals who are in greatest need of PTH treatment, and help to differenti- ate PTH from worsening of a primary headache disorder that occurred following TBI. Although much work needs to be completed before reaching these goals, current studies have already helped to show objective evidence for PTH, a condition that for many could otherwise be considered an “invisible” injury.

Acknowledgement A machine generated summary based on the work of Rau, Jill C.; Dumkrieger, Gina M.; Chong, Catherine D.; Schwedt, Todd J. 2018 in Current Pain and Headache Reports.

Pharmacotherapy for Persistent Posttraumatic Headaches in Children and Adolescents: A Brief Review of the Literature