TBI results in a glutamate release promotional to the extent of the injury: severe trauma results in a larger release, and excess glutamate can overstimulate receptors and cream ion imbalances. Glutamate release may contribute to CSD and central sensitization, worsening PTH symptoms.2
Researchers of one study revealed that “autoantibodies in glutamate receptors in pediatric persistent PTH were elevated even in mTBI.”2 This elevation might be the result of hypoxic or neurometabolic changes in the brain, possibly linked to glutamate receptor overstimulation.
One study of pediatric PTH patients revealed lower levels of ionized magnesium.2 As magnesium helps regulate electrical activity and has neuroprotective effects, this study could indicate a causal relationship between electrolyte abnormalities and PTH.
PTH may “activate an underlying TTH or migraine predisposition” or “accentuate headache patterns pre-existent to trauma.”2 Genetic predisposition appears to play a role in some patients. In particular, carriers of the CACNA1A gene mutation may report severe neurological symptoms after mTBI. These individuals might experience “a genetically lower threshold to symptom development after head trauma.”2
Some individuals with TBI exhibited hormonal dysregulation, including hypothalamic dysregulation.2 Injury to the hypothalamus during head trauma may affect the sleep-wake cycle and circadian rhythms, further contributing to headache symptoms. However, these symptoms are usually seen in moderate-to-severe TBI. The role in PTH and in the mTBI population is less evident.
Clinical Risk Factors
Epidemiological studies2 have identified several factors that appear to increase the risk for PTH after TBI. Women are more prone to PTH, and injury during a motor vehicle accident is also associated with a higher predisposition to PTH.
Further, individuals with PTH often have a history of headaches, lower socioeconomic levels, lower levels of education, a history of medication overuse, or comorbid psychiatric conditions.2 In particular, excessive use of analgesics postconcussion may contribute to PTH, especially among adolescent patients.3
The authors acknowledge that “it is unlikely that a single eventual explanation exists.”3 Instead, PTH and photophobia are likely caused by multiple factors. Symptoms may depend on the extent of the original trauma and the way various injured structures interact with one another.
These overlapping mechanisms make it difficult to identify the role each plays in TBI. Further research is needed, particularly on mTBI.
1. Delic J, Alhilali LM, Hughes MA, Gumus S, Fakhran S. White matter injuries in mild traumatic brain injury and post-traumatic migraines: diffusion entropy analysis. Radiology. 2016;279(3):859-866.
2. Mares C, Dagher JH, Harissi-Dagher M. Narrative review of the pathophysiology of headaches and photosensitivity in mild traumatic brain injury and concussion. Can J Neurol Sci. 2019;46(1):14-22.
3. Heyer GL, Idris SA. Does analgesic overuse contribute to chronic post-traumatic headaches in adolescent concussion patients? Pediatr Neurol. 2014;50(5):464-468.