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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.
Overview
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Written from the paper’s full text.
TL;DR
In a retrospective MRI study of 47 patients with brainstem stroke, coma was associated with lesions clustered in the pontomesencephalic tegmentum, especially the upper pontine tegmentum, whereas non-coma lesions mostly spared the tegmentum or produced small unilateral tegmental damage. The maximum lesion overlap in coma cases coincided with the rostral raphe complex, locus coeruleus, laterodorsal tegmental nucleus, nucleus pontis oralis, parabrachial nucleus, and the white matter between these nuclei.
Key findings
- Of 47 patients, 38 did not have coma: 29 had brainstem damage outside the tegmentum and 9 had very small unilateral tegmental compromise. Of the 9 coma patients, 7 had mostly bilateral tegmental lesions; lesions were in the pons alone in 4 and in the upper pons plus midbrain in 5. The upper pons was always damaged in coma cases, and no coma case had lesions confined to the medulla or midbrain only.
- The maximum overlap territory in coma patients coincided with the rostral raphe complex, locus coeruleus, laterodorsal tegmental nucleus, nucleus pontis oralis, parabrachial nucleus, and intervening white matter; local connections between these nuclei and the ascending central tegmental tract were also severed.
- Four coma patients died in a hyperthermic state (temperature >40°C) without any explainable source of fever; their lesions overlapped in the core of the upper pontine tegmentum, and they had signs of pontine compromise such as Cheyne–Stokes respiration.
- Longer coma duration was associated with bilateral lesions and shorter duration with unilateral lesions; the longest coma was 7 days in patient M.M., who died without gaining consciousness, and none of the cases had persistent vegetative state or loss of consciousness beyond 1 week.
Methods
- Retrospective study: from 236 subjects admitted with stroke and MRI studies, exclusion criteria reduced the sample to 47 patients (19.9%) with brainstem lesions. Lesion boundaries were traced on patient MRIs and transferred onto a 4.7 T MRI template from a control brainstem specimen, which was also cut and analysed histologically; clinical charts and available post-mortem material were used to verify MRI readings.
- Coma was defined as a state of deep sleep with and without stimulations, whereas hypersomnolence was defined as a tendency to sleep when unstimulated but arousable when stimulated. Identification of damaged nuclei was qualitative, based on whether a nucleus location coincided with the lesion territory; no quantification of the degree of nuclear damage was attempted.
Limitations
- The paper states that the records did not include behavioural or cognitive measurements regarding the degree of impaired consciousness, and that no quantification of nuclear damage was attempted because it is beyond current technology. It also notes the limited spatial resolution of the imaging techniques and that the aim was not to identify brainstem nuclei directly with imaging.
- The paper states that exclusion criteria may have selected somewhat “pure” brainstem cases, possibly explaining the absence of coma lasting longer than 7 days; it also states that diffuse CNS inflammation following stroke could not be ruled out as a cause of hyperthermia.
- Evident from the text: the coma group was small (n = 9), the design was retrospective, and the anatomical inference relies on lesion overlap rather than direct causal testing.
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Claims the paper makes
37 Own result · 17 Own interpretation · 15 No full text of the sources · 5 Own method · 4 No basis given · 3 Sources not found · 3 Not checked yet · 1 Check pending
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, regardless of their rostrocaudal level, lesions in the majority of these cases (n = 29) were clustered in the anterior portion of the brainstem, sparing the tegmentum but involving structures such as the cerebral peduncles, the pontine nuclei of the basis pontis or the pyramidal tracts.”
§ Neuroanatomical correlates of brainstem coma > Results
plaincorrelationaln = 29- Asserted: passes — The authors put it forward as true.
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In the paper
“In addition to patient M.M., patients P.H., V.S. and V.R. also died without gaining consciousness (Tables 1 and 3).”
§ Neuroanatomical correlates of brainstem coma > Results
plainn = 4- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These lesions involved the posterior aspect of the tegmentum (Fig. 4).”
§ Neuroanatomical correlates of brainstem coma > Results
plaincorrelationaln = 9- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In cases with coma, the maximum overlap of lesion territories was centred in the core of the upper pontine tegmentum involving the raphe complex (NR), locus coeruleus (LC), laterodorsal tegmental nucleus (LDT), pedunculopontine tegmental nucleus (PPTg), nucleus pontis oralis (PnO) and the parabrachial nucleus (PBN).”
§ Neuroanatomical correlates of brainstem coma > Results
plaincorrelationaln = 9- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Accordingly, patients who died of hyperthermia had signs of pontine compromise such as pinpoint pupils and Cheyne±Stoke respiration.”
§ Neuroanatomical correlates of brainstem coma > Brainstem stroke and fatal hyperthermia
plaincorrelationaln = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We also found that four coma subjects developed hyperthermia and died in the absence of any infections.”
- Also stated in: § Results · plain
“To our surprise, we found that all four cases died in a state of hyperthermia (temperature >40°C) in the absence of any explainable source of fever.”
§ Neuroanatomical correlates of brainstem coma > Abstract
plainn = 4- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that the shortest duration of coma was associated with unilateral lesions, especially when the lesions were non-haemorrhagic (patients T.G. and I.P. compared with patient H.R.).”
§ Neuroanatomical correlates of brainstem coma > Duration of coma in patients with brainstem stroke
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The brainstem lesions observed in the patients are the cause of their coma.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In these cases, the maximum lesion overlap was centred in the core of pontine tegmentum.”
§ Neuroanatomical correlates of brainstem coma > Abstract
plaincorrelationaln = 4- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In summary, none of the 47 cases included in the study had lesions in the hypothalamus, basal forebrain or bilateral cerebral cortex.”
§ Neuroanatomical correlates of brainstem coma > Results
plainn = 47- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among the cases included in the study, 38 had brainstem stroke without loss of consciousness.”
§ Neuroanatomical correlates of brainstem coma > Results
plain- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 28
- Probably not a substantial claim. 15
- The quote only partly states this claim. 1
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Patients T.G. and I.P. were the only coma patients who had acquired unilateral lesions of the tegmentum, and both had the shortest duration of coma (Table 1).”
§ Neuroanatomical correlates of brainstem coma > Results
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In only ®ve cases, a small portion of the tegmentum was affected unilaterally, but the lesions were always in the most anterior portion of the tegmentum affecting structures such as the substantia nigra or the red nucleus.”
§ Neuroanatomical correlates of brainstem coma > Results
plainn = 5- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Neuroanatomical correlates of brainstem coma > Abstract
plaincorrelationaln = 9- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Post-mortem analysis con®rmed the MRI readings and indicated a thrombotic basilar artery with an infarct area in the upper pons that affected the lateral tegmental regions including the corticospinal tracts bilaterally.”
§ Neuroanatomical correlates of brainstem coma > Results
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“None of our cases had persistent vegetative state or loss of consciousness beyond 1 week.”
§ Neuroanatomical correlates of brainstem coma > Duration of coma in patients with brainstem stroke
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In these four cases, brainstem lesions were either in the pons alone (n = 2) or in the pons and the midbrain (n = 2).”
§ Neuroanatomical correlates of brainstem coma > Results
plainn = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Neuroanatomical correlates of brainstem coma > Abstract
plaincorrelationaln = 38- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Comparing the unilateral lesions in non-coma patients with the unilateral lesions in coma patients revealed the following: lesions in comatose patients with unilateral lesions were close to the midline and the posterior tegmentum, while the lesions in non-comatose patients were centred in the lateral and anterior tegmentum.”
§ Neuroanatomical correlates of brainstem coma > Duration of coma in patients with brainstem stroke
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The brainstem lesions observed in the patients are the cause of their coma.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In our study, we found that four cases had died without recovering consciousness and that they all had died in a hyperthermic state in the absence of any obvious cause for their fever.”
§ Neuroanatomical correlates of brainstem coma > Brainstem stroke and fatal hyperthermia
plaincorrelationaln = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Patients P.H., V.S. and V.R. had 2, 5 and 5 days of coma, respectively.”
§ Neuroanatomical correlates of brainstem coma > Results
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Only patient P.H. had haemorrhagic stroke, whereas the other three had non-haemorrhagic infarcts.”
§ Neuroanatomical correlates of brainstem coma > Results
plainn = 4- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The duration of coma in our cases varied signi®cantly: longer duration of coma was associated with bilateral lesions, and shorter duration was associated with unilateral lesions (Tables 1 and 3).”
§ Neuroanatomical correlates of brainstem coma > Results
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“None of the cases with coma had lesions in the medulla, and no cases contained lesions con®ned to the midbrain only.”
§ Neuroanatomical correlates of brainstem coma > Results
plainn = 9- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Lesions in coma cases affected either the midbrain and pontine tegmentum together (n = 5), or only the upper pontine tegmentum without involving the midbrain (n = 4).”
§ Neuroanatomical correlates of brainstem coma > Results
plaincorrelationaln = 9- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Although hyperthermia can be caused by hydrocephalus (Talman et al., 1988) or lesions anywhere between the upper pons and the hypothalamus (Simpson et al., 1993), there is evidence suggesting a strong correlation between fatal hyperthermia and pontine compromise (Wijdicks and St Louis, 1997).”
§ Neuroanatomical correlates of brainstem coma > Brainstem stroke and fatal hyperthermia
What the sources say
- Not checked — no full text of the sourcecites Simpson et al., 1993 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In a recent study, it was found that the dopaminergic cells in the ventral PAG and NR are active during wakefulness, and their lesion causes 20% more sleep (Lu et al., 2002).”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
What the sources say
- Not matchedcites Lu et al., 2002
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
- Not matched
In the paper
“Of note is that these patients developed Cheyne±Stoke respiration and one had pathological sneezing, all suggesting a pontine compromise (Miller et al., 1994).”
§ Neuroanatomical correlates of brainstem coma > Results
What the sources say
- Not checked — no full text of the sourcecites Miller et al., 1994 source
hedgedcorrelationaln = 4- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“They also project to the basal forebrain where widespread projections to the cerebral cortex originate (Smiley et al., 1999).”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
What the sources say
- Not checked — no full text of the sourcecites Smiley et al., 1999 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In other words, we were con®dent that coma in our subjects was due exclusively to the compromise of the brainstem and not the other brain structures.”
§ Neuroanatomical correlates of brainstem coma > Results
boosteddirectn = 47- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A third possibility is that a lesion in the midbrain disrupts the pathways that descend from the rostral structures and target the upper pons.”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
hedgedconditional- Asserted: fails — The authors may not put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The authors may not put it forward as true. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We did not have behavioural and cognitive measurements regarding the quality of consciousness in patients who had not become comatose or had gained consciousness after being in a coma.”
§ Neuroanatomical correlates of brainstem coma > Exclusion criteria were: (i) absence of lesions in the brainstem; (ii) presence of extensive damage to other brain structures; (iii) unavailable MRIs; (iv) poor quality MRIs; or (v) presence of con¯icting
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It could be due to, for instance, the disruption of pathways passing through the midbrain such as those that originate in the upper pons and target the rostral structures, or those that descend from the rostral structures and target the pontine structures.”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, it is conceivable that brainstem lesions compromise the function of the PnO, LC, NR, LDT and PBN and impair their in¯uence on rostral structures, thus halting their orchestrated modulation of the global activity of the brain.”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Rests on an assumption: The anatomical and physiological findings from non-human mammals about brainstem nuclei apply to humans.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Neuroanatomical correlates of brainstem coma > Abstract
plainn = 47- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, our study complements that notion by ®nding that the maximum overlap of coma-causing lesions is centred in the upper pons, and that lesions con®ned to the pons alone can cause coma even in the absence of midbrain damage.”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Although hyperthermia can be caused by hydrocephalus (Talman et al., 1988) or lesions anywhere between the upper pons and the hypothalamus (Simpson et al., 1993), there is evidence suggesting a strong correlation between fatal hyperthermia and pontine compromise (Wijdicks and St Louis, 1997).”
§ Neuroanatomical correlates of brainstem coma > Brainstem stroke and fatal hyperthermia
What the sources say
- Not checked — no full text of the sourcecites Talman et al., 1988 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This impairment could be due to a direct lesion centred in the upper pons from where these nuclei operate, or to a lesion in the midbrain through which the ascending pathways from these nuclei must travel.”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The PnO sends presumably glutamatergic projections to the intralaminar nuclei of the thalamus, which in turn project to various cortical regions (Brodal, 1957;Steriade et al., 1988;Newman and Ginsberg, 1994).”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
What the sources say
- Not matchedcites Brodal, 1957
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites Steriade et al., 1988 source
- Not matchedcites Newman and Ginsberg, 1994
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The application of these criteria reduced the number of suitable subjects to 47 (19.9%).”
§ Neuroanatomical correlates of brainstem coma > Exclusion criteria were: (i) absence of lesions in the brainstem; (ii) presence of extensive damage to other brain structures; (iii) unavailable MRIs; (iv) poor quality MRIs; or (v) presence of con¯icting
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“It is noteworthy that anatomical studies in the early 1950s showed that the PnO is also a major recipient of cortical projections to the `reticular formation' (Brodal, 1957).”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
What the sources say
- Not matchedcites Brodal, 1957
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“The LDT contains cholinergic neurons (Mesulam et al., 1989), which project to several thalamic nuclei including the reticular nucleus of the thalamus (Steriade et al., 1988) and to basal forebrain regions such as the substantia innominata (Muller et al., 1993).”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The identi®cation of damaged nuclei was qualitative, i.e. ®nding whether a nucleus location coincided with the lesion territory.No quanti®cation of the degree of nuclear damage was attempted because this is a task beyond the reach of current state of the art technology.”
§ Neuroanatomical correlates of brainstem coma > Exclusion criteria were: (i) absence of lesions in the brainstem; (ii) presence of extensive damage to other brain structures; (iii) unavailable MRIs; (iv) poor quality MRIs; or (v) presence of con¯icting
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is possible that they could have had longer duration of coma had they survived.”
§ Neuroanatomical correlates of brainstem coma > Duration of coma in patients with brainstem stroke
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“The reticular nucleus of the thalamus, in turn, sends inhibitory projections to other thalamic nuclei (Scheibel et al., 1966;Steriade and Deschenes, 1984;Barth and MacDonald, 1996), thereby functioning as a pacemaker for the thalamic oscillations, which hallmark non-rapid eye movement sleep.”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The PBN is known as an afferent integration site that is involved in many aspects of homeostasis, including thermal, ¯uid, electrolyte and energy balance (Caille et al., 1981;Dick et al., 1994;Saper and Breder, 1994;Menani et al., 1995;Mizusawa et al., 1995;Buritova et al., 1998).”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
What the sources say
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thirdly, our study suggests a neuroanatomical correlate for hyperthermia following brainstem stroke, and raises the possibility that some brainstem lesions are fatal perhaps due to the compromise of the components of the brainstem involved in temperature regulation.”
§ Neuroanatomical correlates of brainstem coma > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The absence of an explainable source of fever in the four hyperthermic coma patients indicates that the hyperthermia is due to the brainstem lesion rather than an undetected infection or other cause.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In brief, our ®nding is in agreement with the classical notion of brainstem coma, but it narrows down the crucial brainstem territory and points to the possibility that, compared with the midbrain, the human upper pons may play a more crucial role in the maintenance of consciousness than the classical notion implies.”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is possible that the lack of cases with long duration of coma among our subjects had to do with the fact that our cases were somewhat `pure' brainstem cases.”
§ Neuroanatomical correlates of brainstem coma > Duration of coma in patients with brainstem stroke
hedgedconditionaln = 236- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The LC and the NR, respectively, are the source of direct noradrenergic and serotonergic projections to most of the cortical mantle (Moore and Bloom, 1979).”
§ Neuroanatomical correlates of brainstem coma > The neuroanatomical correlates of brainstem coma
What the sources say
- Not checked — no full text of the sourcecites Moore and Bloom, 1979 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
The normal brainstem specimen used as a template is representative of the brainstem anatomy of the patients with brainstem stroke.
“First, a normal brainstem specimen was selected randomly from a collection of 610 brains from the University of Iowa brain collections at Dr Gary Van Hoesen's laboratory.The donor had died of stomach cancer without any neurological or psychiatric history.”
The paper relies on this without support.
The anatomical and physiological findings from non-human mammals about brainstem nuclei apply to humans.
“As shown in Fig. 1, studies in non-human mammals have shown that these nuclei have the anatomical and physiological means to induce global changes in the electrophysiological activity of the brain.”
The paper relies on this without support.
The absence of an explainable source of fever in the four hyperthermic coma patients indicates that the hyperthermia is due to the brainstem lesion rather than an undetected infection or other cause.
“To our surprise, we found that all four cases died in a state of hyperthermia (temperature >40°C) in the absence of any explainable source of fever.”
The paper relies on this without support.
The brainstem lesions observed in the patients are the cause of their coma.
“This design made it possible for us to compare brainstem lesions that cause short lapses of consciousness with those that cause longer duration of coma.”
The paper relies on this without support.
The control brainstem specimen used for charting nuclei is representative of normal human brainstem anatomy.
“The control brainstem specimen used in our study was cut on a freezing microtome into 50 mm thick sections.”
The paper relies on this without support.
The MRI chartings transferred to the template brainstem MRI atlas accurately represent the lesion boundaries in each patient.
“Once the MRI chartings were transferred to the template brainstem MRI atlas, the overlapping regions were coded with different colours.”
The paper relies on this without support.
The absence of an obvious cause for fever in the four patients means their hyperthermia was not due to infection or other systemic causes.
“they all had died in a hyperthermic state in the absence of any obvious cause for their fever.”
The paper relies on this without support.
The patients included in the study are representative of patients with brainstem coma generally.
“As noted, from a pool of 236 subjects, we included only 19.9% of the cases.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
Experimental — accuracy not yet measuredIn the citing paper
“Evidence that the AAn is essential for consciousness comes from experimentally induced lesions in rodents3 and cats4 and mapping of brainstem infarctions in humans.5”
From Disruption of the ascending arousal network in acute traumatic disorders of consciousness (2019) · cites this paper as [5]
In the citing paper
“In addition, several brainstem nuclei (locus coeruleus, dorsal raphe, median raphe, pedunculopontine nucleus, parabrachial nucleus), non-specific thalamic nuclei, hypothalamus, and basal forebrain are also included in the ARAS system (Aston-Jones et al., 2001; Parvizi and Damasio, 2003; Fuller et al., 2011).”
From The Ascending Reticular Activating System from Pontine Reticular Formation to the Thalamus in the Human Brain (2013) · cites this paper as Parvizi and Damasio, 2003
In the citing paper
“Conventional brain MRI, functional neuroimaging techniques, electrophysiological methods, and MR spectroscopy have been used in studies of the ARAS in the human brain (Parvizi and Damasio, 2003; Schiff, 2006; Tshibanda et al., 2009, 2010; Gawryluk et al., 2010).”
From The Ascending Reticular Activating System from Pontine Reticular Formation to the Thalamus in the Human Brain (2013) · cites this paper as Parvizi and Damasio, 2003
In the citing paper
“Similarly, our findings are consistent with previous work linking dorsolateral pontine tegmentum lesions to coma in humans1,4 and coma-like outcomes in animals.9”
From Thalamic strokes that severely impair arousal extend into the brainstem (2018) · cites this paper as [4]
In the citing paper
“Early models of an ascending reticular activating system (ARAS) originating from diffuse neurons in the brainstem reticular formation have been revised to include discrete brainstem regions and individual nuclei that are preferentially involved in maintaining a state of wakefulness.1–5”
From Thalamic strokes that severely impair arousal extend into the brainstem (2018) · cites this paper as [4]
In the citing paper
“this is not consistent with past evidence that ischemic strokes and other lesions limited to the brainstem cause coma.1,4”
From Thalamic strokes that severely impair arousal extend into the brainstem (2018) · cites this paper as [4]
In the citing paper
“These findings are consistent with previous research highlighting the role of the brainstem and posterior hypothalamus as critical regions in the arousal pathway,1–4”
From Thalamic strokes that severely impair arousal extend into the brainstem (2018) · cites this paper as [4]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Neuroanatomical correlates of brainstem coma > Abstract
“four coma subjects developed hyperthermia and died in the absence of any infections”
§ Neuroanatomical correlates of brainstem coma > Table 3. Short summary of clinical data regarding the patients with brainstem coma
“VR Admitted in the early morning for bacterial endocarditis.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Neuroanatomical correlates of brainstem coma > Abstract
“a very small and unilateral compromise of the tegmentum (n = 9)”
§ Neuroanatomical correlates of brainstem coma > Results
“In only ®ve cases, a small portion of the tegmentum was affected unilaterally”
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Metadata
- 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
- OpenAlex
- W2045226019
- Semantic Scholar
- ed5a0f5772d8594a017b9bd04a0e5a297dd75efe
- 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 › Clinical Neurology › Traumatic Brain Injury Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Clinical 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-11 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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