Neuroanatomical correlates of brainstem coma

Abstract

The brainstem tegmentum, including the reticular formation, contains distinct nuclei, each of which has a set of chemical, physiological and anatomical features. Damage to the brainstem tegmentum is known to cause coma, the most radical disturbance of consciousness. However, it has remained unclear which nuclei within the tegmentum are crucial for the maintenance of consciousness in humans. Accordingly, we initiated a retrospective study of MRIs obtained from 47 patients with brainstem stroke. The lesion boundaries were charted on patient MRIs and transferred onto a corresponding series of 4.7 T MRIs obtained from a control brainstem specimen that later was cut on a freezing microtome and analysed histologically. In addition, medical charts and available post-mortem materials were used to obtain relevant clinical and anatomical data to verify the MRI readings in each case. We found that in the 38 patients who did not have coma, brainstem damage either was located outside the tegmentum (n = 29) or produced a very small and unilateral compromise of the tegmentum (n = 9). In contrast, in patients who had coma (n = 9), the lesions in the tegmentum were mostly bilateral (n = 7) and were located either in the pons alone (n = 4) or in the upper pons and the midbrain (n = 5). The maximum overlap territory of the lesions coincided with the location of the rostral raphe complex, locus coeruleus, laterodorsal tegmental nucleus, nucleus pontis oralis, parabrachial nucleus and the white matter in between these nuclei. We also found that four coma subjects developed hyperthermia and died in the absence of any infections. In these cases, the maximum lesion overlap was centred in the core of pontine tegmentum. Our findings suggest that lesions confined to the upper pons can cause coma in humans even in the absence of damage to the midbrain. The findings also point to the brainstem nuclei whose lesions are likely to be associated with loss of consciousness and fatal hyperthermia in humans.