Mild traumatic brain injury is a leading cause of death and disability worldwide with 42 million cases reported annually, increasing the need to understand the underlying pathophysiology because this could help guide the development of targeted therapy. White matter, particularly the corpus callosum, is susceptible to injury.
Animal models suggest stretch-induced mechanoporation of the axonal membrane resulting in ionic shifts and altered sodium ion distribution. The purpose of this study was to compare the distribution of total sodium concentration in the corpus callosum between patients with mild traumatic brain injury and controls using sodium (23Na) MR imaging.
Eleven patients with a history of mild traumatic brain injury and 10 age- and sex-matched controls underwent sodium (23Na) MR imaging using a 3T scanner. Total sodium concentration was measured in the genu, body, and splenium of the corpus callosum with 5-mm ROIs; total sodium concentration of the genu-to-splenium ratio was calculated and compared between patients and controls.
Higher total sodium concentration in the genu (49.28 versus 43.29 mmol/L, P = .01) and lower total sodium concentration in the splenium (which was not statistically significant; 38.35 versus 44.06 mmol/L, P = .08) was seen in patients with mild traumatic brain injury compared with controls. The ratio of genu total sodium concentration to splenium total sodium concentration was also higher in patients with mild traumatic brain injury (1.3 versus 1.01, P = .001).
Sodium concentration in symptomatic patients with mild traumatic brain injury
Complex differences are seen in callosal total sodium concentration in symptomatic patients with mild traumatic brain injury, supporting the notion of ionic dysfunction in the pathogenesis of mild traumatic brain injury.
The total sodium concentration appears to be altered beyond the immediate post-injury phase, and further work is needed to understand the relationship to persistent symptoms and outcome.
Many medications may affect sodium homeostasis. The most relevant ones were specifically screened and included in the chart review. Patient 5 was on the antidepressant escitalopram (selective serotonin reuptake inhibitor).
There are a few recent reports of escitalopram causing a syndrome of inappropriate antidiuretic hormone secretion and hyponatremia. Our patient exhibited no signs of the syndrome of inappropriate antidiuretic hormone secretion and had normal serum chemistry values. Patient 3 was treated with lamotrigine, a central nervous system voltage-gated sodium channel blocker, for posttraumatic dystonia. In this subject, the TSC genu/splenium ratio among the mTBI group was the closest to that of the control cohort.
This study shows complex differences in the TSC in the CC in symptomatic patients with mTBI compared with age- and sex-matched healthy controls. Specifically, the TSC in the genu of the CC was elevated. Further work is needed to understand the relationship between TSC change and symptom resolution or outcome prediction.