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Abstract
Background In patients with severe traumatic brain injury (TBI), coma is associated with impaired subcortical arousal mechanisms. However, it is unknown which nuclei involved in arousal (arousal nuclei) are implicated in coma pathogenesis and are compatible with coma recovery.
Methods We mapped an atlas of arousal nuclei in the brainstem, thalamus, hypothalamus, and basal forebrain onto 3 tesla susceptibility-weighted images (SWI) in 12 patients with acute severe TBI who presented in coma and recovered consciousness within 6 months. We assessed the spatial distribution and volume of SWI microbleeds and evaluated the association of microbleed volume with the duration of unresponsiveness and functional recovery at 6 months.
Results There was no single arousal nucleus affected by microbleeds in all patients. Rather, multiple combinations of microbleeds in brainstem, thalamic, and hypothalamic arousal nuclei were associated with coma and were compatible with recovery of consciousness. Microbleeds were frequently detected in the midbrain (100%), thalamus (83%), and pons (75%). Within the brainstem, the microbleed incidence was largest within the mesopontine tegmentum (e.g., pedunculotegmental nucleus, mesencephalic reticular formation) and ventral midbrain (e.g., substantia nigra, ventral tegmental area). Brainstem arousal nuclei were partially affected by microbleeds, with microbleed volume not exceeding 35% of brainstem nucleus volume on average. Compared to microbleed volume within nonarousal brainstem regions, the microbleed volume within arousal brainstem nuclei accounted for a larger proportion of variance in the duration of unresponsiveness and 6-month Glasgow Outcome Scale–Extended scores.
Conclusion These results suggest resilience of arousal mechanisms in the human brain after severe TBI.
Glossary
- CLi=
- caudal linear raphe;
- CnF=
- cuneiform nucleus;
- DR=
- dorsal raphe;
- GCS=
- Glasgow Coma Scale;
- GOSE=
- Glasgow Outcome Scale–Extended;
- ICU=
- intensive care unit;
- isRt=
- isthmic reticular formation;
- LC=
- locus coeruleus;
- LDTg=
- laterodorsal tegmental nucleus;
- MEMPRAGE=
- multiecho magnetization-prepared rapid gradient echo;
- MNI=
- Montreal Neurological Institute;
- MnR=
- median raphe;
- mRt-p1Rt=
- mesencephalic reticular formation and p1 reticular formation;
- PAG=
- periaqueductal gray;
- PMnR=
- paramedian raphe nucleus;
- PTg=
- pedunculotegmental nucleus;
- SN=
- substantia nigra;
- SWI=
- susceptibility-weighted imaging;
- T1W=
- T1-weighted;
- TBI=
- traumatic brain injury;
- VTA-PBP=
- ventral tegmental area with parabrachial pigmented nucleus
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 53
CME Course: NPub.org/cmelist
- Received December 3, 2020.
- Accepted in final form April 9, 2021.
- © 2021 American Academy of Neurology
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