| Article Access Statistics|
| Viewed||316 |
| Printed||8 |
| Emailed||0 |
| PDF Downloaded||4 |
| Comments ||[Add] |
Click on image for details.
|Year : 2022 | Volume
| Issue : 2 | Page : 670-675
Brain Death Diagnosis in Primary Posterior Fossa Lesions
Institute of Neurology and Neurosurgery, Havana, Cuba
|Date of Submission||02-May-2020|
|Date of Decision||05-May-2020|
|Date of Acceptance||10-Jul-2020|
|Date of Web Publication||3-May-2022|
Institute of Neurology and Neurosurgery Department of Clinical Neurophysiology 29 y D, Vedado, La Habana 10400
Source of Support: None, Conflict of Interest: None
Background: New controversies have raised on brain death (BD) diagnosis when lesions are localized in the posterior fossa.
Objective: The aim of this study was to discuss the particularities of BD diagnosis in patients with posterior fossa lesions.
Materials and Methods: The author made a systematic review of literature on this topic.
Results and Conclusions: A supratentorial brain lesion usually produces a rostrocaudal transtentorial brain herniation, resulting in forebrain and brainstem loss of function. In secondary brain lesions (i.e., cerebral hypoxia), the brainstem is also affected like the forebrain. Nevertheless, some cases complaining posterior fossa lesions (i.e., basilar artery thrombotic infarcts, or hemorrhages of the brainstem and/or cerebellum) may retain intracranial blood flow and EEG activity. In this article, I discuss that if a posterior fossa lesion does not produce an enormous increment of intracranial pressure, a complete intracranial circulatory arrest does not occur, explaining the preservation of EEG activity, evoked potentials, and autonomic function. I also addressed Jahi McMath, who was declared braindead, but ancillary tests, performed 9 months after initial brain insult, showed conservation of intracranial structures, EEG activity, and autonomic reactivity to “Mother Talks” stimulus, rejecting the diagnosis of BD. Jahi McMath's MRI study demonstrated a huge lesion in the pons. Some authors have argued that in patients with primary brainstem lesions it might be possible to find in some cases partial recovery of consciousness, even fulfilling clinical BD criteria. This was the case in Jahi McMath.
Keywords: Ancillary tests, Brain death, brain-dead, brainstem lesions, brainstem lesions, cerebral blood flow (CBF), EEG, Jahi McMath, posterior fossa, posterior fossa
Key Message: In this article, I discuss that if a posterior fossa lesion does not produce an enormous increment of intracranial pressure, a complete intracranial circulatory arrest doesn't occur, explaining EEG preservation, as well as evoked potentials, and autonomic function.
|How to cite this article:|
Machado C. Brain Death Diagnosis in Primary Posterior Fossa Lesions. Neurol India 2022;70:670-5
Brain death (BD) has been progressively wide-reaching accepted beginning since the late 1950s.,,,,,,,,,,,,,,,,,,, BD outlines medical and legal standards, and its determination is based on guidelines for children, and adults, that established an orderly set of clinical criteria assessed at the bedside, and the use or not of ancillary tests. However, argumentative braindead cases have recently raised up new disputes, arguing up-to-date BD criteria by questioning accepted medical standards.,,,,,,,,
Three standards of death on neurological grounds have been debated in the last decades: whole brain, brainstem death and higher brain.,,,,,,, Higher brain defenders defended the concept of as the “the loss of consciousness”, (definition) associated to the permanent destruction of the neocortex (criterion), or “higher brain”.,,, I discussed that “consciousness does not bear a simple one-to-one relationship with higher or lower brain structures, and therefore, the higher brain formulation is wrong, because the definition [consciousness] does not correspond directly to the criterion [neocortex]”.,,,
James Bernat claimed that “the formulation of whole-brain death provides the most congruent map for our correct understanding of the concept of death”. This author argued that “the irreversible cessation of the clinical functions of the brain represents death because the brain is responsible for the functioning of the organism as a whole”. Hence, this author recently proposed to move from “whole brain criterion” to “brain as a whole criterion”, to fulfil the “definition of death as the cessation of the organism as a whole”.,
The United States President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research quoted Bernat and his colleagues' research to adopt the whole-brain formulation of death,,,,, by all US states in the Uniform Determination of Death Act (UDDA).
McGee and Gardiner, stated that the lawful basis for death declaration in the UK and Commonwealth countries, is fairly well settled, based on the medical standards provided by the Royal Colleges' Code of Practice, mainly based on the Christopher Pallis' brainstem death view. This author considered that there were practical reasons to promote this view, “a dead (i.e., irreversibly non-functioning) brainstem can be diagnosed at bedside, without resort of complicated investigations, and it predicts inevitable asystole within a short while”. Pallis emphasized that the “capacity for consciousness” and “respiration” are the two hallmarks of life of the human being, and that brainstem death predicts an inescapable asystole.
The brainstem standard was adopted by Common Wealth and other countries. For example, India passed a law in 1994 to legalize brain-stem death., India supports the UK concept of brain-stem death, and hence the Transplantation of Human Organs (THO) Act was passed by Indian parliament in 1994, legalizing the brain-stem death standard in 1995. Afterwards, THO rules were written which describe brain-stem death certification process.,, The majority of the Indian states have passed this act in their assemblages, although a few states have yet include it., Furthermore, an important document from the state of Maharashtra has recently completed the way to notify braindead cases.,,
Brainstem death view defenders have not considered necessary EEG or CBF as confirmatory tests in BD determinations.,, I have argued that the physio-pathological appraisal of consciousness generation and respiration provides the basis for rejecting Pallis' concept of brainstem death.,, Besides, the latency for occurring an asystole after BD declaration, can be by augmented by continuous life support,,,, and in some rare cases [i.e., pregnancy] be prolonged to weeks or months, or extremely to years.,,
The conceptual and practical difference in BD determination between the USA and UK has been known as the “transatlantic divide”., Wijdicks, who was the main author of the American Academy of Neurology (AAN) Guidelines on BD, stated that “the irreversible absence of functions of the brainstem is the necessary and sufficient component of BD, and this can be assessed and diagnosed clinically at the bedside”. This is fully in concordance with the brainstem and not with the whole brain view of BD.,,,,, As I have already argued, the President's Commission recommended to adopt the whole brain view by all US states.
| » Brainstem Lesions|| |
The presence of a primary lesion localized to the posterior fossa sets a main controversial debate on BD determination. A primary supratentorial brain lesion usually provokes a rostrocaudal transtentorial brain herniation syndrome, resulting on brain function impairment in both cerebral hemispheres and the brainstem. When a secondary brain lesion [i.e., cerebral hypoxia] is present, the brainstem is also affected like the forebrain. Nevertheless, some patients, who have a primary infratentorial brain lesion [for example, in basilar artery thrombosis or large brainstem or cerebellar bleeds], without a significant increment of intracranial pressure, may retain CBF and EEG activity.,,,,,,,,,
Grigg et al. studied 56 patients fulfilling BD clinical criteria, and 20% preserved EEG activity, suggesting that EEG is not required as ancillary test to confirm BD. Nonetheless, apnea test was not performed in one-third or more of the cases, and these authors did not describe which PCO2 thresholds they took in account for confirming BD in the remaining patients. Pathologic studies were realized in only two cases which demonstrated ischemic brainstem lesions, relatively sparing the cerebral cortex. The pathologic examination of the rest of the cases was not described.
Ferbert reported preservation of EEG and visual evoked potentials [VEP] in a patient with a hematoma in the cerebellum and the pons, who fulfilled brain-stem death clinical criteria. Hence, this author stated that EEG should be mandatory for BD diagnosis in the presence of posterior fossa lesions. Esteban et al. also reported 5 patients, fulfilling clinical BD criteria, who showed long long-lasting EEG activity. Three of those patients had primary posterior fossa lesions.
From a series of 161 braindead cases, Varela et al. studied three cases (represented 1.9%), and added another patient from a different hospital. These four patients presented posterior fossa injuries, and therefore fulfilled the UK-BD clinical criteria, including the apnea test. All four patients suffered from catastrophic posterior fossa injuries, and therefore fulfilled UK-BD criteria, including the apnea test. These 4 patients showed preservation of supratentorial CBF, which vanished after a period of between 2 and 6 days, then permitting BD diagnosis, according to the US accepted standard of whole-brain criteria. These authors concluded that in patients complaining primary posterior fossa catastrophic lesions, fulfilling USA-BD clinical criteria, would characteristically progress from conserving, to losing supratentorial CBF. Therefore, the authors stated that if CBF assessment is used as a confirmatory test, those patients are not dissimilar from those braindead patients with supratentorial lesions. Nonetheless, the challenge of the aforementioned cases focuses on determining when the patients were braindead according to the US or UK-BD criteria.
In fact, the main difference in applying “whole brain” or “brainstem” standards BD criteria, is precisely when a primary posterior fossa lesion is present. Dattatray-Dhanwate precisely described the causes and pathophysiology of brain-stem death in a paper entitled “Brainstem death: A comprehensive review in Indian perspective”. This author emphasized that “traumatic injury to the head [e.g., road accident], subarachnoid hemorrhage and ischemic stroke are the most common causes of brain-death”, among others like intracerebral hemorrhage, hypoxic-ischemic encephalopathy, etc. Hence, Dattatray-Dhanwate comprehensively described the way how increased ICP lessens cerebral perfusion pressure and CBF, and provokes transtentorial herniation and coning at foramen magnum occur. Nonetheless, this author does not describe when primary posterior fossa lesions don't produce a significant increment of ICP and CBF, with subsequent preservation of CBF and EEG.
Wijdicks commented about a study of 56 cases fulfilling clinical BD criteria, that 20% retained EEG activity, lasting up to 168 hours. This author also stated that the EEG sensitivity and specificity in BD determination is about 90%. Wijdicks remarked there is not one patient fulfilling brain-stem death criteria who has survived, but this statement is related to prognosis and not to diagnosis.
Varela et al. commented that in the case of isolated brainstem lesions, sparing the mesopontine tegmental reticular formation, this condition would theoretically lead to a fully apneic locked-in syndrome, which imitates brain-stem death., Walter et al. affirmed that hence, a patient with a primary posterior fossa injury could retain some degree of consciousness, lasting some time.
Varela et al. also stated that there are no reports of braindead patients, properly diagnosed under either the whole brain or brainstem views, who have shown consciousness recovery or breathing recommence. Then, they erroneously stated that persistent supratentorial CBF or EEG activity does not indicate remaining brain function. This was not the case in Jahi McMath.,
Moreover, experimental studies in animals with important mesopontine tegmental reticular formation neuronal damage, quasi-normal EEG with major alpha, beta, or theta activity is not certain to occur. Therefore, these authors remarked that confirmatory tests should be mandatory for diagnosing BD, to find no EEG activity, or even better no CBF. Hence, in this condition BD diagnosis has to be doubted, and as long as EEG activity is present, and it cannot be excluded that patients might be at least partially conscious.,, Arguing about brain-stem death formulation, Bernat pointed out the possibility of a “profound locked-in syndrome” in which awareness might be retained in the absence of brain-stem activity.
These reports of near normal EEG, preserved supratentorial CBF, and cortical visual evoked potentials in cases with posterior fossa injury, lead to harsher BD codes in Europe. These tougher BD codes require mandatory demonstration of electrocortical silence, one or both absent CBF [assessed by cerebral angiography, perfusion scintigraphy, or Doppler sonography], when a primary posterior fossa lesions is present.,,,,,,,
Jahi McMath: A case with an enormous lesion in the posterior fossa
Jahi McMath suffered a immense hemorrhage inside her respiratory ways, as a surgical complication, leading to a cardiorespiratory arrest. CPR permitted to recover spontaneous circulation, but an extensive hypoxic encephalopathy was caused by the event. She was declared braindead. After a legal litigation, her body was released to her mother, allowing to continue mechanical ventilation and intravenous fluids. Then, Jahi McMath was moved to the New Jersey State, where relatives can decide to accept a cardio-respiratory or a neurological standard of death.,,,,,
In September 2014, I was invited to travel to New Jersey, as an expert advisor, to evaluate ancillary tests prescribed by a US licensed neurologist.
Summarizing my findings in Jahi McMath, after 9 months of her initial diagnosis,
- Clinical examination. The patient was supine on a bed, with her eyes closed, and demonstrated “no signs of awareness of self and/or environment”. Neurological examination demonstrated a complete loss of brainstem reflexes [corneal, oculo-cephalic, oculo-vestibular, gag, and cough]. The patient was unable to trigger a ventilator and the patient's relatives did not give permission to perform an additional apnea test, beyond the original performed nine months prior. The Coma Recovery Scale-Revised––CRS-R total score was: 3 (reproducible movement to command).
- Her MRI showed preservation of intracranial structures, despite the presence of enormous abnormalities, documented 9 months after a cardiac arrest: preservation of cortical and brainstem gross anatomy, with non-expected relative slight atrophy, and a huge lesion in the brainstem: posterior regions of the pons, lateralized to the left side.
- EEG activity over 2 μV of amplitude was clearly recorded. Moreover, delta–theta range predominant activity was found.
- Heart rate variability (HRV) methodology showed the preservation of all bands. “Mother Talks” stimulation demonstrated autonomic reactivity.
Preservation of intracranial structures was demonstrated nine months after initial insult. It has been widely described that braindead patients have a complete absence of CBF.,,,,, As this patient had preserved intracranial structures, it is possible to remark that her CBF was not completely absent.
Bernat recently emphasized that “the most confident way to demonstrate that the global loss of clinical brain functions is irreversible is to show the complete absence of intracranial blood flow.” After a few minutes of complete intracranial circulatory arrest, neurons are irreversibly injured, and are widely damaged in about 20-30 minutes, when CBF fully stops, with normal body temperature. Therefore, a total absence of CBF for more than 30 minutes demonstrates irreversible brain damage in BD. The justification is that a full intracranial circulatory arrest during this time causes a total brain infarct.,,, Dalle Ave and Bernat proposed that “to uphold the standard of clinical certainty, we advocate proving the whole-brain criterion of death by showing the absence of intracranial blood flow”.
Therefore, the first argument against that the diagnosis of BD in Jahi McMath, 9 months after the initial diagnosis, was the preservation of intracranial structures., The preservation of EEG activity is in concordance with other cases that I have previously referred of main lesions in the posterior fossa. This also might explain why some functions of the central autonomic nervous system were preserved.
The MRI of Jahi McMath showed a huge lesion in the pons. Hence, a number of reasons might explain the intermittent conscious responses in this patient: relative integrity of the upper part of the brainstem, paramedian thalamus, and cortex, as well as the partial sparing of the mesopontine tegmental reticular formation. She probably might also had preserved its connections to the temporo-parieto-occipital associative cortices, and/or its ventral pathway to the cortico-cortical projection systems, and parts of the associative cerebral cortices. These findings might explain the intermittent conscious responses in this patient.,,
Therefore, Jahi McMath was not braindead, or in an unresponsive wakefulness state (UWS), previously termed persistent vegetative state [PVS], or in a minimally conscious state [MCS], or in a locked-in syndrome [LIS].
I concluded that Jahi represented a new state of disorder of consciousness, non-previously described, that I have termed: “responsive unawakefulness syndrome” (RUS).
It is evident that the presence of primary posterior fossa lesions enforces the needs of “aligning the criterion and tests for brain death”. When a brainstem lesion does not provoke an important increment of intracranial pressure there may be not a full absence of CBF, explaining preservation of EEG activity, evoked potentials, and autonomic function in those cases.,,,,,,
Some authors have argued then that patients with primary brainstem lesions it might be possible to find in some cases partial recover of consciousness, even fulfilling clinical BD criteria. This was the case in Jahi McMath., Further research and discussion are necessary about the use or not of confirmatory tests in BD diagnosis, in the presence of primary posterior fossa lesions.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient's mother has/have given her consent for her images and other clinical information to be reported in the journal. The patient's mother understands that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Bernat JL, Dalle Ave AL. Aligning the criterion and tests for brain death. Camb Q Healthc Ethics 2019;28:635-41.
Bernat JL, Delmonico FL. Restoring activity of pig brain cells after death does not invalidate the determination of death by neurologic criteria or undermine the propriety of organ donation after death. Transplantation 2019;103:1295-7.
Bernat JL, Brust JC. Strategies to improve uniformity in brain death determination. Neurology 2019;92:401-2.
Shewmon DA. Brain death: A conclusion in search of a justification. Hastings Cent Rep 2018;48(Suppl 4):S22-5.
Machado C. Historical evolution of the brain death concept: Additional remarks. J Crit Care 2014;29:867.
Machado C. Death as a biological notion. J Crit Care 2014;29:1119-20.
Machado C. Reader response: Variability in reported physician practices for brain death determination. Neurology 2020;94:97.
Machado C. Reader response: Brain death, the determination of brain death, and member guidance for brain death accommodation requests: AAN position statement. Neurology 2019;93:946-7.
Machado C, Estevez M. Reader response: Practice current: When do you order ancillary tests to determine brain death? Neurol Clin Pract 2018;8:364.
Machado C, Estevez M, DeFina PA, Leisman G. Reader response: An interdisciplinary response to contemporary concerns about brain death determination. Neurology 2018;91:535.
Lewis A. Response to Machado, et al
. re: Jahi McMath. Neurocrit Care 2018;29:523-4.
Lewis A. Reconciling the case of Jahi McMath. Neurocrit Care 2018;29:20-2.
Machado C, Estevez M, Rodriguez R, Perez-Nellar J, Chinchilla M, DeFina P, et al
. Zolpidem arousing effect in persistent vegetative state patients: Autonomic, EEG and behavioral assessment. Curr Pharm Des 2014;20:4185-202.
Lewis A, Bernat JL, Blosser S, Bonnie RJ, Epstein LG, Hutchins J, et al
. Author response: An interdisciplinary response to contemporary concerns about brain death determination. Neurology 2018;91:536-8.
Shah A, Jhawar SS, Nunez M, Goel A, Goel A. Brainstem anatomy: A study on the basis of the pattern of fiber organization. World Neurosurg 2020;134:e826-46.
Tan CY, Ahmad SB, Goh KJ, Latif LA, Shahrizaila N. Overlap of Bickerstaff brainstem encephalitis/Guillain-Barre syndrome simulating brain death. Neurol India 2018;66:1475-80.
] [Full text]
Mohod V, Kondwilkar B, Jadoun R. An institutional study of awareness of brain-death declaration among resident doctors for cadaver organ donation. Indian J Anaesth 2017;61:957-63.
] [Full text]
Dhanwate AD. Brainstem death: A comprehensive review in Indian perspective. Indian J Crit Care Med 2014;18:596-605.
] [Full text]
Sodhi R, Khanduri S, Nandha H, Bhasin D, Mandal AK. Brain death--think twice before labeling a patient. Am J Emerg Med 2012;30:1321.e1-2.
Nakagawa TA, Ashwal S, Mathur M, Mysore MR, Bruce D, Conway EE Jr, et al
. Guidelines for the determination of brain death in infants and children: An update of the 1987 Task Force recommendations. Crit Care Med 2011;39:2139-55.
Wijdicks EF. Determining brain death in adults. Neurology 1995;45:1003-11.
Goodwin M. Revisiting death: Implicit bias and the case of Jahi McMath. Hastings Cent Rep 2018;48(Suppl 4):S77-80.
Shewmon DA. The case of Jahi McMath: A neurologist's view. Hastings Cent Rep 2018;48(Suppl 4):S74-6.
Shewmon DA. Truly reconciling the case of Jahi McMath. Neurocrit Care 2018;29:165-70.
Truog RD. Lessons from the case of Jahi McMath. Hastings Cent Rep 2018;48(Suppl 4):S70-3.
Truog RD, Berlinger N, Zacharias RL, Solomon MZ. Brain death at fifty: Exploring consensus, controversy, and contexts. Hastings Cent Rep 2018;48(Suppl 4):S2-5.
Truog RD. Biological, legal, and moral definitions of brain death-reply. JAMA 2018;320:1494-5.
Truog RD, Pope TM, Jones DS. The 50-year legacy of the harvard report on brain death. JAMA 2018;320:335-6.
Truog RD. Defining death-making sense of the case of Jahi McMath. JAMA 2018;319:1859-60.
Machado C. Brain Death: A Reappraisal. New York: Spinger Science+Bussiness Media, LLC; 2007.
Machado C. Consciousness as a definition of death: Its appeal and complexity. Clin Electroencephalogr 1999;30:156-64.
Bernat JL. A conceptual justification for brain death. Hastings Cent Rep 2018;48(Suppl 4):S19-21.
Bernat JL. A defense of the whole-brain concept of death. Hastings Cent Rep 1998;28:14-23.
Bernat JL. Brain death. Occurs only with destruction of the cerebral hemispheres and the brain stem. Arch Neurol 1992;49:569-70.
Bernat JL. The definition, criterion, and statute of death. Semin Neurol 1984;4:45-51.
Bernat JL, Culver CM, Gert B. Definition of death. Ann Intern Med 1984;100:456.
Youngner SJ. Defining death. A superficial and fragile consensus. Arch Neurol 1992;49:570-2.
Machado C. Death on neurological grounds. J Neurosurg Sci 1994;38:209-22.
Veatch RM. The impending collapse of the whole-brain definition of death. Hastings Cent Rep 1993;23:18-24.
Cranford RE, Smith DR. Consciousness: The most critical moral (constitutional) standard for human personhood. Am J Law Med 1987;13:233-48.
Korein J, Machado C. Brain death: Updating a valid concept for 2004. Adv Exp Med Biol 2004;550:1-14.
Machado C. Is the concept of brain death secure? In: Zeman A, Emanul L, editorss. Ethical Dilemmas in Neurology. London: W. B. Saunders Company; 2000. p. 193-212.
Bernat JL. The biophilosophical basis of whole-brain death. Soc Philos Policy 2002;19:324-42.
Bernat JL. The whole-brain concept of death remains optimum public policy. J Law Med Ethics 2006;34:35-43.
Huang AP, Bernat JL. The organism as a whole in an analysis of death. J Med Philos 2019;44:712-31.
Bernat JL, Culver CM, Gert B. Definition of death. Ann Intern Med 1981;95:652.
Determination of death (Uniform Determination of Death Act of 1981); natural death (Natural Death Act of 1981). LEXIS District of Columbia code 1981.
McGee A, Gardiner D. Differences in the definition of brain death and their legal impact on intensive care practice. Anaesthesia 2019;74:569-72.
DIAGNOSIS OF BRAIN DEATH: Statement issued by the Honorary Secretary of the Conference of Medical Royal Colleges and their Faculties in the United Kingdom on 11th
October 1976. Ann R Coll Surg Engl 1977;59:170-2.
Government of India. Ministry of Law JaCALD. The Transplantation of Human Organs Act, 1994. Central Act 42 of 1994. 1994.
Government of India. Ministry of Law JaCALDND. The Transplantation of Human Organs Rules, 1995 (GSR NO. 51(E), dr. (1995 Feb 04)) (As amended vide GSR 571(E) 2008 Jul 31. 1995.
Government of Maharashtra PHD. Government Resolution No. MAP2012/C.R.289/AROGYA-6. 2012.
Government of India. Ministry of Law JaCALDND. Transplantation of Human Organs (Amendment) Rules. 2008. 2008.
Pallis C. Further thoughts on brainstem death. Anaesth Intensive Care 1995;23:20-3.
Pallis C. Brainstem death: The evolution of a concept. Semin Thorac Cardiovasc Surg 1990;2:135-52.
Pallis C. ABC of brain stem death. The arguments about the EEG. Br Med J (Clin Res Ed) 1983;286:284-7.
Shewmon DA. “Brainstem death,” “brain death” and death: A critical re-evaluation of the purported equivalence. Issues Law Med 1998;14:125-45.
Shewmon DA. Chronic “brain death”: Meta-analysis and conceptual consequences. Neurology 1998;51:1538-45.
Lewis A, Bonnie RJ, Pope T, Epstein LG, Greer DM, Kirschen MP, et al
. Determination of death by neurologic criteria in the United States: The case for revising the Uniform Determination of Death Act. J Law Med Ethics 2019;47 (4_suppl):9-24.
Boran OF, Yazar FM, Bakacak M, Soylu D, Yazar N, Oksuz H. Assessment of somatic support process for pregnant brain death patients occurring in a transition country between Asia and Europe from medical, ethical, legal and religious aspects. J Relig Health 2019. doi: 10.1007/s10943-019-00952-1.
Lewis A, Varelas P, Greer D. Pregnancy and brain death: Lack of guidance in U.S. hospital policies. Am J Perinatol 2016;33:1382-7.
Wijdicks EF. The transatlantic divide over brain death determination and the debate. Brain 2012;135(Pt 4):1321-31.
Wijdicks EF. Determining Brain Death. Continuum (Minneap Minn) 2015;21 (5 Neurocritical Care):1411-24.
Machado C, Estevez M, DeFina PA, Leisman G. Response to Lewis A: Reconciling the case of Jahi Mcmath. Neurocrit Care 2018;29:521-2.
Roth C, Ferbert A, Matthaei J, Kaestner S, Engel H, Gehling M. Progress of intracranial pressure and cerebral perfusion pressure in patients during the development of brain death. J Neurol Sci 2019;398:171-5.
Manara A, Varelas P, Wijdicks EF. Brain death in patients with “isolated” brainstem lesions: A case against controversy. J Neurosurg Anesthesiol 2019;31:171-3.
Varelas PN, Brady P, Rehman M, Afshinnik A, Mehta C, Abdelhak T, et al
. Primary posterior fossa lesions and preserved supratentorial cerebral blood flow: Implications for brain death determination. Neurocrit Care 2017;27:407-14.
Varelas PN. Brainstem or entire brain-based declaration of death: Is there a difference? Pract Neurol 2016;16:85-6.
Varelas PN, Lewis A. Modern approach to brain death. Semin Neurol 2016;36:625-30.
Walter U, Fernandez-Torre JL, Kirschstein T, Laureys S. When is “brainstem death” brain death? The case for ancillary testing in primary infratentorial brain lesion. Clin Neurophysiol 2018;129:2451-65.
Grigg MM, Kelly MA, Celesia GG, Ghobrial MW, Ross ER. Electroencephalographic activity after brain death. Arch Neurol 1987;44:948-54.
Ferbert A, Buchner H, Ringelstein EB, Hacke W. Isolated brain-stem death. Case report with demonstration of preserved visual evoked potentials (VEPs). Electroencephalogr Clin Neurophysiol 1986;65:157-60.
Esteban A, Traba J, Prieto J, Roldán R, Santiago S. Prolonged EEG activity in brainstem death. In: Machado C, editor. B
rain Death (Proceedings of the Second International Symposium on Brain Death). Developments in Neurology. Amsterdam: Elsevier Science, BV; 1995. p. 151-6.
Wijdicks EF. The clinical determination of brain death: Rational and reliable. Semin Neurol 2015;35:103-4.
Machado C, DeFina PA, Estevez M, Leisman G, Rodriguez R, Presitigiacomo C, et al
. A reason for care in the clinical evaluation of function on the spectrum of consciousness. J Funct Neurol Rehabil Ergon Rehabil 2017;4:542-56.
Laureys S. The neural correlate of (un) awareness: Lessons from the vegetative state. Trends Cogn Sci 2005;9:556-9.
Walter U, Bruderlein U, Gloger M, Mann S, Walther U. [Brain death diagnosis after sedation with propofol or sufentanil. Recommendations for the usage of toxicological analytics]. Med Klin Intensivmed Notfmed 2015;110:145-9.
Sawicki M, Solek-Pastuszka J, Chamier-Cieminska K, Walecka A, Walecki J, Bohatyrewicz R. Computed tomography perfusion is a useful adjunct to computed tomography angiography in the diagnosis of brain death. Clin Neuroradiol 2019;29:101-8.
Rudolf J, Haupt WF, Neveling M, Grond M. Potential pitfalls in apnea testing. Acta Neurochir (Wien) 1998;140:659-63.
Sawicki M, Solek-Pastuszka J, Chamier-Cieminska K, Walecka A, Bohatyrewicz R. Accuracy of computed tomographic perfusion in diagnosis of brain death: A prospective cohort study. Med Sci Monit 2018;24:2777-85.
Sawicki M, Solek-Pastuszka J, Jurczyk K, Skrzywanek P, Guzinski M, Czajkowski Z, et al
. Original protocol using computed tomographic angiography for diagnosis of brain death: A better alternative to standard two-phase technique? Ann Transplant 2015;20:449-60.
Forderreuther S, Angstwurm H. [Re: W.F. Haupt, W. Holling: Diagnosis of brain death: Medical and legal aspects under the transplantation law of the German Republic Fortschr Neurol Psychiat 2002;70:583-590]. Fortschr Neurol Psychiatr 2003;71:221; author reply 221.
Frowein RA, Ganshirt H, Hamel E, Haupt WF, Firsching R. [Diagnosis of brain death in primary infratentorial brain damage]. Nervenarzt 1987;58:165-70.
Haupt WF. [Brain death]. Med Klin (Munich) 1996;91:46.
Haupt WF. [Multimodality evoked potentials and brain death. Prerequisites, findings and problems]. Nervenarzt 1987;58:653-7.
Luce JM. The uncommon case of Jahi McMath. Chest 2015;14:1144-51.
Pedicelli A, Bartocci M, Lozupone E, D'Argento F, Alexandre A, Garignano G, et al
. The role of cervical color Doppler ultrasound in the diagnosis of brain death. Neuroradiology 2019;61:137-45.
Kramer AH. Ancillary testing in brain death. Semin Neurol 2015;35:125-38.
Joffe AR, Lequier L, Cave D. Specificity of radionuclide brain blood flow testing in brain death: Case report and review. J Intensive Care Med 2010;25:53-64.
Kang KM, Yun TJ, Yoon BW, Jeon BS, Choi SH, Kim JH, et al
. Clinical utility of arterial spin-labeling as a confirmatory test for suspected brain death. AJNR Am J Neuroradiol 2015;36:909-14.
Marrache F, Megarbane B, Pirnay S, Rhaoui A, Thuong M. Difficulties in assessing brain death in a case of benzodiazepine poisoning with persistent cerebral blood flow. Hum Exp Toxicol 2004;23:503-5.
Bernat JL. On irreversibility as a prerequisite for brain death determination. Adv Exp Med Biol 2004;550:161-7.
Ingvar DH. Brain death--total brain infarction. Acta Anaesthesiol Scand Suppl 1971;45:129-40.
Dalle Ave AL, Bernat JL. Using the brain criterion in organ donation after the circulatory determination of death. J Crit Care 2016;33:114-8.
Zuckier LS. Radionuclide evaluation of brain death in the post-mcmath era. J Nucl Med 2016;57:1560-8.
Dalle Ave AL, Bernat JL. Inconsistencies between the criterion and tests for brain death. J Intensive Care Med 2020;35:772-80.
Varelas P. Brain death determination: Still a lot to learn, still a lot to do…. Neurocrit Care 2014;21:373-5.
Wagner W. SEP testing in deeply comatose and brain dead patients: The role of nasopharyngeal, scalp and earlobe derivations in recording the P14 potential. Electroencephalogr Clin Neurophysiol 1991;80:352-63.