Prevalence of Traumatic Findings on Routine MRI in a Large Cohort of Professional Fighters

Discussion

This study presents a large number of fighters who have been exposed to known cumulative head trauma and scanned on the same 3T MR imaging machine by using standardized conventional imaging protocols. We found that CSP and CV occurred more frequently in fighters than in age- and sex-matched controls, whereas there was no statistical difference between groups in the occurrence of NSWMCs. CMHs occurred more frequently in fighters than controls, but this was not statistically significant.

The presence of CMH as a distinct pathologic finding was first discussed in 1924¹⁷ and was soon related to a theory of traumatic brain injury characteristically seen in boxers.¹⁸ Mechanisms of traumatic injury at the microscopic level involve strain (relative stretch) of neural tissue, and the severity of injury depends on the magnitude of the strain. At the smallest magnitude, tissue is elastic and there is no damage; at intermediate magnitudes, there are transient and reversible alterations of membrane potentials (concussions); at the highest magnitudes, irreversible damage and chronic change occur. Along this spectrum are concomitant tissue reactions, including vasogenic and cytotoxic edema (seen acutely on DWI), microhemorrhages (seen chronically on SWI), and focal gliosis and demyelination (seen chronically on FLAIR). Because the fighters in this study were not imaged in the acute setting, imaging findings would likely be manifest as chronic changes on SWI and FLAIR.

Although the reason for microhemorrhages occurring in fighters may seem self-evident, the relatively low prevalence of CMH might be surprising given the large number of fighters known to receive knockout blows and concussions. In fact, the radiologic appearance of the brain among most fighters with known multiple concussions is normal on conventional MR imaging. However, damage may be present below the capability of conventional MR imaging. For example, in other sports with a high incidence of repetitive head trauma (eg, American football), researchers have established the existence of chronic traumatic encephalopathy during postmortem examinations, which can only be seen under the microscope.¹⁹ Therefore, any damage evident on MR imaging likely represents the “tip of the iceberg,” with much greater microscopic damage extending beyond any visible damage. For many fighters, it is possible that damage and dysfunction accumulate within this microscopic range, which could explain the discrepancy between known mild traumatic brain injury and MR images with clinically normal findings. Some portion of this range could be explored with higher field MR imaging (eg, 7T MR imaging with higher resolution and sensitivity to susceptibility effects) or with advanced MR imaging techniques such as high-resolution DTI.²⁰

In our study, the CMH prevalence among fighters was 4.2%; this is lower than the prevalence observed in previous studies (7.1% and 9.5%)^4,5 and was not statistically significant from that in our controls. This finding is likely in part due to the study being underpowered with a relatively small number of controls versus fighters, as supported by post hoc power analysis with an α of .05 that showed a power (1-β) of 18.5%. Generally, a power of 80% is considered adequate in most cases and would have required around double the control population to achieve adequate power, given an α of .05 and an unchanged incidence of CMH in fighters and controls. In regard to the raw percentage CMH, a comparison study of retired National Football League players also demonstrated a prevalence of 9%.²¹ The prevalence in our study may have been lower because we excluded susceptibility-positive healthy variants such as capillary telangiectasia and vascular malformations and nontraumatic pathologies such as cavernous malformations. If we had included these findings, the prevalence of CMH would have been 7.9%. The type of imaging sequence used may also have played a role. T2* and SWI are most commonly used to assess for the presence of CMH. The higher prevalence of CMH observed by Hasiloglu et al⁵ may have been linked to their use of SWI, which is a newer and more sensitive sequence than T2* imaging.

The earliest studies to assess the occurrence of CSP in boxers used pneumoencephalography and found evidence of CSP in 6 of 9 boxers (67%),²² a prevalence slightly higher than we observed in our study (53%). In studies of American football players, Koerte et al¹⁴ and Gardner et al² observed a CSP prevalence of 92% and 94%, respectively. In addition, their prevalence of CSP in healthy controls was 57% and 18%, respectively, with only the latter value comparable with our prevalence of 20%. These differences may be partially explained by differences between the sports in the mechanism of head trauma; boxing blows to the head cause a rotational acceleration, whereas football blows to the head cause a linear acceleration. Other unknown mechanisms could also explain these differences, including genetic differences related to athlete selection. The mean age of each patient population may have also affected the results. The cohort of 72 retired football players in the study by Koerte et al¹⁴ had a higher mean age of 57 years compared with the mean patient age in our study (30 years). The age-dependent prevalence of CSP was illustrated in a large postmortem series of 1032 human brains (from nontraumatic brain injury victims), which demonstrated a CSP prevalence of 18% for boys younger than 10 years of age, 13% for men 25–35 years of age (similar to our age group of controls at 20%), and 24% for men older than 50 years of age.²³ Another postmortem series demonstrated a CSP prevalence of 18%,²⁴ whereas an MR imaging study of incidental findings of CSP in the pediatric population demonstrated a much lower prevalence of 1.14%, with a mean patient age of 15 years.

These factors do not entirely explain the widely varying range of CSP prevalence observed in previous studies, however. For example, 2 previous MR imaging studies demonstrated a CSP prevalence in adults of 2.1%²⁵ and 68%.²⁶ In another study among football players, the CSP prevalence was 7%, but the researchers included only large CSPs.²¹ This finding suggests that there may be considerable variation in how CSP has been defined in the literature. In our study, most CSPs were very small, appearing as small triangles or trapezoids just posterior to the genu of the corpus callosum (an average length of 10.9 mm in fighters). For future investigations, it would be helpful to derive a consensus opinion regarding size definitions for CSP.

The mechanism for increased CSP/CV prevalence and length with head trauma is still unknown. Pathologists have described 4 types of cava, including noncommunicating and communicating, further complicating the issue.²⁴ One theory for the increase in length and prevalence of CSP/CV among patients with head trauma is that transient increased intracranial pressure results in passage of CSF through small tears in septal leaflets.¹⁰ Such tears were described in the postmortem examination of a former boxer as multiple perforations of the septal leaflets with a latticelike appearance.²² These tears could be accentuated by shear forces resulting from rapid rotation of the head, allowing CSF to enter the potential space of the septum pellucidum and slowly dissect a cavity. A second theory involves ex vacuo expansion of the potential space in the septum pellucidum due to central volume loss caused by repeated trauma.^2,27 Future research might benefit from dedicated microscopic postmortem examinations of former athletes.

An interesting hypothesis that may explain the disparity of published CSP prevalence is that traumatic brain injury does not necessarily increase the prevalence of CSP, but the size. Using MR imaging in a pediatric cohort of 98 survivors of traumatic brain injury and 34 healthy controls, Silk et al²⁸ concluded that there was no statistical difference between groups in the prevalence of CSP; however, CSPs were larger among patients with head trauma than among controls. In a similar postmortem study of patients with and without head trauma, the CSP prevalence was 38% and 54%, respectively.²⁹ However, patients with head trauma demonstrated a distinct morphology of CSP termed a “cleft cavum,” which was comorbid with diffuse axonal injury and represented 13% of all head trauma victims. The researchers suggested that this finding represents the acute effect of severe head trauma superimposed on an underlying baseline prevalence of nontraumatic CSP.

In our study, the prevalence of NSWMC was similar between fighters and controls; this finding suggests that no sequelae from repeated head trauma manifested as focal FLAIR hyperintensity. A recent study of college ice hockey players also found no evidence of new FLAIR lesions in patients with concussions,³⁰ and in a study of 46 military veterans with mild traumatic brain injuries, Clark et al³¹ found that there was no significant increased prevalence of FLAIR WM lesions in patients versus controls. These findings suggest that standard MR imaging sequences such as FLAIR are not useful for the diagnosis of mild traumatic brain injury,³² perhaps because the size of the focal traumatic lesions is too small to be visible on these sequences.

This study had several limitations, including the relative imbalance between the large number of fighters and the smaller number of healthy controls. A greater number of controls would have increased the significance of our results, particularly in the case of CMH, which has a low baseline prevalence. There are only a few relevant studies in the literature that have a large number of healthy controls imaged for CMH. In particular, the studies of Hähnel at al⁴ and Hasiloglu et al⁵ together imaged 58 controls, none of whom had any CMH. Although many other studies reported higher numbers of controls, these studies were not applicable because of their use of T2* gradient recalled-echo sequences rather than SWI,³³ poor age matches (typically elderly controls), or underlying disease states such as hypertension, degenerative disease, multiple sclerosis, and amyloid angiopathy.^{34⇓⇓–37}