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Cited by 400Traumatic Brain Injury ResearchSleep and Wakefulness ResearchTraumatic Brain Injury and Neurovascular Disturbances

Neuroanatomical correlates of brainstem coma

Parvizi, J.·2003·Brain
DOI 10.1093/brain/awg166
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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.

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  • In patients with brainstem stroke, acute coma was associated with MRI lesions in the pontine tegmentum extending from the upper pons into the midbrain.

    “Similarly, in patients with brainstem stroke, Parvizi and Damasio found that acute coma was associated with magnetic resonance imaging (MRI) lesions in the pontine tegmentum extending from the upper pons into the midbrain.7”

    From Damage to Arousal-Promoting Brainstem Neurons with Traumatic Brain Injury (2016) · cites this paper as [7]

    The Results report that coma in patients with brainstem stroke was associated with lesions of the upper pontine tegmentum. But only five of nine coma cases also had midbrain involvement; four had lesions confined to the upper pons. Describing the lesions as extending into the midbrain omits that distinction. (LLM, conf=0.88)

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  • It remains unknown whether TBI injures these specific arousal-promoting neurons.

    “Still, it remains unknown whether TBI injures these specific arousalpromoting neurons.”

    From Damage to Arousal-Promoting Brainstem Neurons with Traumatic Brain Injury (2016) · cites this paper as [7]

    The Abstract and Results examine brainstem lesions in patients with stroke, and the Introduction says it was unclear which brainstem nuclei maintain consciousness in humans. Neither addresses whether traumatic brain injury (TBI) injures those neurons. Searches for TBI, traumatic injury, and trauma did not find a passage that settles the claim. (LLM, conf=0.73)

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Cites

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3 of the 74 references couldn’t be matched to a known paper.

Research works printed but not linked: 9

  1. Bester H, Bourgeais L, Villanueva L, Besson JM, Bernard JF. Differential projections to the intralaminar and gustatory thalamus from the parabrachial area: a PHA-L study in the rat. J Comp Neurol 1999; 405: 421±49.
  2. Bremer F. Cerveau `isole Â' et physiologie du sommeil. C R Soc Biol 1935; 118: 1235±41.
  3. Buritova J, Besson JM, Bernard JF. Involvement of the spinoparabrachial pathway in in¯ammatory nociceptive processes: a c-Fos protein study in the awake rat. J Comp Neurol 1998; 397: 10±28.
  4. Krout KE, Loewy AD. Parabrachial nucleus projections to midline and intralaminar thalamic nuclei of the rat. J Comp Neurol 2000a; 428: 475±94.
  5. Krout KE, Loewy AD. Periaqueductal gray matter projections to midline and intralaminar thalamic nuclei of the rat. J Comp Neurol 2000b; 424: 111±41.
  6. Moore RY. The reticular formation: monoamine neuron systems. In: Hobson JA, Brazier MAB, editors. The reticular formation revisisted. New York: Raven Press; 1980. p. 67±81.
  7. Newman DB, Ginsberg CY. Brainstem reticular nuclei that project to the thalamus in rats: a retrograde tracer study. Brain Behav Evol 1994; 44: 1±39.
  8. Pace-Shott EF, Hobson JA. The neurobiologicy of sleep. Nature Rev Neurosci 2002; 3: 591±605.
  9. Paxinos G, Huang XF. Atlas of the human brainstem. San Diego: Academic Press; 1995.

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Authors
Parvizi, J.
Affiliations
University of Iowa (US)
Corresponding author
Parvizi, J.
ORCID
Parvizi, J.
Venue
Brain
Publisher
Oxford University Press (OUP)
Published
2003-04-22
Volume
126
Issue
7
Pages
1524-1536
ISSN
  • 0006-8950 (ISSN-L)
  • 1460-2156
DOI
10.1093/brain/awg166
OpenAlex
W2045226019
Cited by
400
References
74
Citations by year
2026: 17 · 2025: 27 · 2024: 27 · 2023: 23 · 2022: 16 · 2021: 19 · 2020: 18 · 2019: 20 · 2018: 36 · 2017: 13 · 2016: 20 · 2015: 14 · 2014: 14 · 2013: 30 · 2012: 15
FWCI
3.52
Type
journal article
Language
en
Open access
closed
Locations
  • Brain (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • G. Harold and Leila Y. Mathers Foundation
  • University of Illinois at Urbana-Champaign
Topics
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords
brainstem infarction, reticular formation, consciousness, pontine tegmentum, locus coeruleus, laterodorsal tegmental nucleus, parabrachial nucleus, hyperthermia, lesion localization, midbrain
MeSH terms
Adult, Aged, Brain Stem, Coma, Female, Fever, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Pons, Reticular Formation, Retrospective Studies, Stroke

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