Re: Disconnection of the ascending arousal system in traumatic coma. J Neuropathol Exp Neurol 2013;72: 505-523.

In the June issue, Edlow et al used a cutting edge imaging tool to demonstrate tracts in the autopsied brain of a victim of traumatic coma (1). Histologic study of the same brain showed widespread axonal damage in keeping with the long-standing understanding that closed head injury results in diffuse axonal injury throughout the brain (2). The imaging analysis showed, however, that only 1 set of pathways, that is, the ''arousal'' pathways connecting brainstem nuclei to the basal forebrain and to thalamic intralaminar and reticular nuclei, was completely disrupted. They proposed that traumatic coma is specifically related to this disconnection rather than to widespread axonal damage throughout the brain, as has been suggested by others studying nonhuman primates (2). I should like to point out that the proposal of Edlow et al is consistent with the findings I reported with coworkers in 1981 (3). In that study, we showed that more than 80% of patients who died as a result of head trauma had midbrain lesions. This was consistent with evoked potential data gathered within 72 hours of injury from 165 patients that showed that midbrain deficits were associated with death or poor recovery while those without midbrain deficits made good to moderate recoveries. Because our article focused on the prognostic implications of midbrain lesions in the context of widespread diffuse axonal damage, the relationship of our findings to coma may not have been appreciated. Indeed, the word ''coma'' was only used when describing exclusion criteria: ''Patients excludedI.included those whose coma was thought to be due to alcohol, drug overdose, or epilepsy.'' Thus, it was implied (and true) that all of our auto-psied patients were believed to be in coma from the moment they were found and remained so until death. Consistent with their diagnosis of coma was the fact that, on arrival at the hospital, 21 of the 23 patients with midbrain le-sions at autopsy had impaired or absent oculocephalic reflexes and 19 had absent or diminished pupillary reflexes. A study of pigs has also suggested that immediate coma after traumatic brain injury is dependent on axonal damage in the brainstem (4). No relationship was found between coma and the extent of axonal damage in other parts of the brain. That study, like the recent report by Edlow et al, did not recognize that we reported the essential role of midbrain injury in producing posttraumatic coma. It seems important …