Exploring naturally occurring clinical subgroups of post-traumatic headache

DOI: https://doi.org/10.1186/s10194- 020- 1080- 2

Abstract-Summary There is no evidence available from the International Classification of Headache Disorders (ICHD) based classification between persistent and acute PTH based on clinical phenotypes.

The following variables were extracted from each patient’s chart: diagnosis of PTH as dependent variable, and predictor variables as age, sex, history of migraine, loss of consciousness during head injury, pre-existing psychological history, dura- tion of PTH and new PTH-associated comorbidities (e.g. new onset vertigo, post- traumatic stress disorder).

Logistic regression was employed to identify clinical phenotypes predicting per-

sistent PTH.

Two-step cluster analysis was conducted to identify naturally occurring PTH

subgroups.

A total of 300 patients were included (150 acute, 150 persistent PTH) with a

median age of 47 years (IQR 31, 59) and female: male ratio of 2.7:1.

Pre-existing psychological history (standardized beta 0.16), history of migraine (0.20), new PTH-associated comorbidities (0.23) and medication overuse (0.37) statistically significantly predicted the presence of persistent PTH (p < 0.0001).

Clustering analysis revealed PTH subgrouping comparable to ICHD-based clas- sification: 140 patients in Cluster 1 (76% persistent PTH) and 160 patients in Cluster 2 (83% acute PTH).

Four distinct clusters were found within persistent PTH. Pre-existing psychological history, history of migraine, new PTH-associated comorbidities and medication overuse predicted the occurrence of persistent PTH as well as two naturally occurring PTH clusters correlating to acute and persis- tent PTH.

Extended: Two-step cluster analysis was selected since the data were mostly

categorical.

Two-step cluster analysis results revealed 2 clusters of PTH i.e. 140 (46.7%)

patients assembled in Cluster 1 and 160 (53.7%) patients in Cluster 2.

A total of 500 electronic patient charts were reviewed. A total of 295 patients was required to achieve 80% power involving 8 predictor

variables with α error probability of 0.05 and small effect size f2 of 0.05.

Pre-existing psychological history (e.g. depression, anxiety, bipolar, post- traumatic stress disorder) was found in 27 (18%) patients of the acute PTH group compared to 78 (52%) patients in the persistent PTH (OR  =  5, 95% CI 3, 8.3; p < 0.0001).

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5 Future Directions

Introduction The diagnosis of acute versus persistent PTH is based on an arbitrary cutoff selec- tion of 3 months of headache duration, greater than 3 months for persistent PTH and lesser than 3 months for acute PTH [76].

A prior population-based study identified that history of traumatic brain injury, being injured under the influence of alcohol, and history of acute PTH were predic- tors for persistent PTH [117].

Information, we wanted to test the hypothesis that exposure to clinical predic- tors, such as medication overuse and psychological symptoms are associated with persistent PTH compared to acute PTH.

In this hospital-based study, we explored the clinical predictors that may be more

likely associated with persistent versus acute PTH.

We conducted clustering analysis to identify naturally-occurring subgroups of

PTH and compare them with ICHD-3 classification of acute versus persistent.

Methods To PTH diagnosis (acute and persistent), the following variables were extracted from each patient’s chart: age, sex, history of migraine, loss of consciousness during head injury, cause of head injury (e.g. fall, being hit with an object, car accident), pre-existing psychological history, duration of PTH, new PTH-associated comor- bidities (e.g. new onset vertigo, post-traumatic stress disorder), and medication overuse.

Since our study was a retrospective design, odds ratio (OR) statistics were used to measure the odds of having persistent versus acute PTH in those presenting with different clinical variables (e.g. history of migraine, pre-existing psychological his- tory, medication overuse, new PTH-associated comorbidities).

Predictor variables (age, sex, loss of consciousness, history of migraine, pre- existing psychological history, new PTH-associated comorbidities, repeated head injuries, medication overuse) were tested in one block to determine their predictive capacity while controlling for other predictors in the model.

Results Fifty-nine (40%) persistent PTH patients had a history of migraine compared to only 8 (5%) acute PTH patients (RR = 2.4, 95% CI 2, 3; p < 0.0001).

History of repeated head injury was seen in 37 (25%) of the persistent PTH patients compared to only 8 (5%) of the acute PTH patients (OR = 5.8, 95% CI 2.6, 13; p < 0.0001).

Only 1 (0.007%) acute PTH patient had medication overuse in contrast to 58 (39%) patients in the persistent PTH group (RR = 2.6, 95% CI: 2.2, 3.0; p < 0.0001). Pre-existing psychological history (e.g. depression, anxiety, bipolar, post- traumatic stress disorder) was found in 27 (18%) patients of the acute PTH group compared to 78 (52%) patients in the persistent PTH (OR  =  5, 95% CI 3, 8.3; p < 0.0001).

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Post-concussion Syndrome

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Discussion Pre-existing psychological history, history of migraine, new PTH-associated comor- bidities and medication overuse predicted the occurrence of persistent PTH.

Cluster 4 persistent PTH patients may also be having increased natural tolerance to pain behavior as evidenced by the cluster’s relatively lower prevalence of psycho- logical comorbidity, medication overuse, and migraine history.

This suggests that a history of headache may predispose patients in developing

persistent PTH after a head injury.

From our study, patients in the persistent PTH group suffered from multiple new PTH-associated comorbidities, including neck pain, vertigo, back pain, autonomic disturbance, anxiety, depression and cognitive impairment.

Although a previous clinical-based study in PTH patients reported higher preva- lence of tension-type headache than migraine [19], tension-type headache was rarely documented or labeled as a pre-existing diagnosis in our study.

Our clinical-based study setting may not give the true population burden of pre-

existing tension-type headache in PTH patients.

Conclusion and Future Direction A pre-existing psychological history, history of migraine, new PTH-associated comorbidities and medication overuse predicted the occurrence of persistent PTH.

Our study has raised a few interesting questions: Would there be a difference in clinical outcome between patients who have medication overuse versus no medica- tion overuse in the development of PTH.

Pre-existing psychological history, history of migraine, new PTH-associated comorbidities and medication overuse were found to be associated with persis- tent PTH.

Machine learning tools can be developed based on our clustering results using clinical variables such as pre-existing psychological history, history of migraine, new PTH-associated comorbidities and medication overuse.

Acknowledgement A machine generated summary based on the work of Chan, T. L. H.; Woldeamanuel, Y. W. 2020 in The Journal of Headache and Pain.

Imaging Post-Traumatic Headache