When is “brainstem death” brain death? The case for ancillary testing in primary infratentorial brain lesion

[en] The widely accepted concept of brain death (BD) comprises the demonstration of irreversible coma in combination with the loss of brainstem reflexes and irreversible apnea. In some countries the combined clinical finding of coma, apnea, and loss of all tested brainstem reflexes (“brainstem death”) is sufficient for diagnosing BD irrespective of the primary location of brain lesion. The present article aims to substantiate the need for ancillary testing in patients with primary infratentorial brain lesions. Anatomically, the “brainstem-death” syndrome can theoretically occur without relevant lesion of the mesopontine tegmental reticular formation (MPT-RF). Thus, a brainstem lesion may cause an apneic total locked-in syndrome, a rare syndrome with preserved capability for consciousness, mimicking “brainstem death”. Findings in animals and humans have shown that alpha- or alpha/theta- EEG patterns in case of isolated brainstem lesion indicate intactness of relevant parts of the MPT-RF. In such patients the presence of irreversible coma has to be doubted, and the potential capacity for some degree of consciousness cannot be excluded as long as the EEG activity persists. Consequently the demonstration of either ancillary finding, electro-cortical inactivity or, preferably, cerebral circulatory arrest, is mandatory for diagnosing BD in patients with a primary infratentorial brain lesion.

Research Center/Unit :

Coma Science Group

Disciplines :

Neurology

Author, co-author :

Walter, Uwe; Department of Neurology, University of Rostock, Rostock, Germany, Center for Transdisciplinary Neurosciences Rostock (CTNR), University of Rostock, Rostock, Germany

Fernández-Torre, José Luis; Department of Clinical Neurophysiology, Marqués de Valdecilla University Hospital, Santander, Spain, Biomedical Research Institute (IDIVAL), Santander, Spain

Kirschstein, Timo; Department of Neurology, University of Rostock, Rostock, Germany, Oscar Langendorff Institute of Physiology, University of Rostock, Rostock, Germany

Laureys, Steven ; Université de Liège - ULiège > GIGA : Coma Group

Language :

English

Title :

When is “brainstem death” brain death? The case for ancillary testing in primary infratentorial brain lesion

Publication date :

2018

Journal title :

Clinical Neurophysiology

ISSN :

1388-2457

eISSN :

1872-8952

Publisher :

Elsevier Ireland Ltd

Volume :

129

Issue :

Pages :

2451-2465

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 30 May 2020

Statistics

Number of views

266 (4 by ULiège)

Number of downloads

603 (3 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

Academy of the Medical Royal Colleges. A code of practice for the diagnosis and confirmation of death. London: Academy of Medical Royal Colleges. http://aomrc.org.uk/wp-content/uploads/2016/04/Code_Practice_Confirmation_Diagnosis_Death_1008-4.pdf, 2008 (accessed 04 March 2018).
Accad, M., Of wholes and parts: A Thomistic refutation of “Brain Death”. Linacre Q 82 (2015), 217–234.
Afifi, A.K., Bergman, R.A., Functional Neuroanatomy: Text and Atlas. 1998, McGraw-Hill Professional, New York.
Aflalo, T., Kellis, S., Klaes, C., Lee, B., Shi, Y., Pejsa, K., et al. Neurophysiology. Decoding motor imagery from the posterior parietal cortex of a tetraplegic human. Science 348 (2015), 906–910.
Alcaro, A., Carta, S., Panksepp, J., The affective core of the self: a neuro-archetypical perspective on the foundations of human (and animal) subjectivity. Front Psychol, 8, 2017, 1424.
Aleman, B., Merker, B., Consciousness without cortex: a hydranencephaly family survey. Acta Paediatr 103 (2014), 1057–1065.
Altwegg-Boussac, T., Schramm, A.E., Ballestero, J., Grosselin, F., Chavez, M., Lecas, S., et al. Cortical neurons and networks are dormant but fully responsive during isoelectric brain state. Brain 140 (2017), 2381–2398.
Arduini, A., Moruzzi, G., Olfactory arousal reactions in the cerveau isole cat. Electroencephalogr Clin Neurophysiol 5 (1953), 243–250.
Babiloni, C., Pistoia, F., Sarà, M., Vecchio, F., Buffo, P., Conson, M., et al. Resting state eyes-closed cortical rhythms in patients with locked-in-syndrome: an EEG study. Clin Neurophysiol 121 (2010), 1816–1824.
Bai, Y., Xia, X., Kang, J., Yang, Y., He, J., Li, X., TDCS modulates cortical excitability in patients with disorders of consciousness. Neuroimage Clin 15 (2017), 702–709.
Batini, C., Moruzzi, G., Palestini, M., Rossi, G.F., Zanchetti, A., Persistent patterns of wakefulness in the pretrigeminal midpontine preparation. Science 128 (1958), 30–32.
Batini, C., Moruzzi, G., Palestini, M., Rossi, G.F., Zanchetti, A., Effects of complete pontine transections on the sleep-wakefulness rhythm: the midpontine pretrigeminal preparation. Arch Ital Biol 97 (1959), 1–12.
Batsel, H.L., Electroencephalographic synchronization and desynchronization in the chronic “cerveau isole” of the dog. Electroencephalogr Clin Neurophysiol 12 (1960), 421–430.
Bauer, G., Gerstenbrand, F., Rumpl, E., Varieties of the locked-in syndrome. J Neurol 221 (1979), 77–91.
Beecher, H., A definition of irreversible coma: report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death. JAMA 205 (1968), 337–340.
Bernat, J.L., Chronic disorders of consciousness. Lancet 367 (2006), 1181–1192.
Bichat, X., Recherches physiologiques sur la vie et la mort. 1800, Brosson, Gabon et Co., Paris.
Blanco, L., Yuste, J.E., Carrillo-de Sauvage, M.A., Gómez, A., Fernández-Villalba, E., Avilés-Olmos, I., et al. Critical evaluation of the anatomical location of the Barrington nucleus: relevance for deep brain stimulation surgery of pedunculopontine tegmental nucleus. Neuroscience 247 (2013), 351–363.
Blend, M.J., Pavel, D.G., Hughes, J.R., Tan, W.S., Lansky, L.L., Toffol, G.J., Normal cerebral radionuclide angiogram in a child with electrocerebral silence. Neuropediatrics 17 (1986), 168–170.
Bohatyrewicz, R., Bohatyrewicz, A., Zukowski, M., Marzec-Lewenstein, E., Biernawska, J., Solek-Pastuszka, J., et al. Reversal to whole-brain death criteria after 15-year experience with brain stem death criteria in Poland. Transplant Proc 41 (2009), 2959–2960.
Boly, M., Tshibanda, L., Vanhaudenhuyse, A., Noirhomme, Q., Schnakers, C., Ledoux, D., et al. Functional connectivity in the default network during resting state is preserved in a vegetative but not in a brain dead patient. Hum Brain Mapp 30 (2009), 2393–2400.
Boly, M., Moran, R., Murphy, M., Boveroux, P., Bruno, M.A., Noirhomme, Q., et al. Connectivity changes underlying spectral EEG changes during propofol-induced loss of consciousness. J Neurosci 32 (2012), 7082–7090.
Bonelli, R.M., Prat, E.H., Bonelli, J., Philosophical considerations on brain death and the concept of the organism as a whole. Psychiatr Danub 21 (2009), 3–8.
Bremer, F., Cerveau 'isolé' et physiologie du sommeil. CR Soc Biol (Paris) 118 (1935), 1235–1241.
Britt, C.W. Jr, Raso, E., Gerson, L.P., Spindle coma, secondary to primary traumatic midbrain hemorrhage. Electroencephalogr Clin Neurophysiol 49 (1980), 406–408.
Brown, R.E., Basheer, R., McKenna, J.T., Strecker, R.E., McCarley, R.W., Control of sleep and wakefulness. Physiol Rev 92 (2012), 1087–1187.
Bruno, M.A., Pellas, F., Schnakers, C., Van Eeckhout, P., Bernheim, J., Pantke, K.H., et al. Le Locked-In Syndrome: la conscience emmurée. Rev Neurol (Paris) 164 (2008), 322–335.
Bruno, M.A., Bernheim, J.L., Ledoux, D., Pellas, F., Demertzi, A., Laureys, S., A survey on self-assessed well-being in a cohort of chronic locked-in syndrome patients: happy majority, miserable minority. BMJ Open, 1, 2011, e000039.
Buchner, H., Schuchardt, V., Reliability of electroencephalogram in the diagnosis of brain death. Eur Neurol 30 (1990), 138–141.
Burns, J.D., Manno, E.M., Wijdicks, E.F., An unusual cause of fixed dilated pupils after cardiac surgery. Neurocrit Care 9 (2008), 370–373.
Cabrer, C., Domínguez-Roldan, J.M., Manyalich, M., Trias, E., Paredes, D., Navarro, A., et al. Persistence of intracranial diastolic flow in transcranial Doppler sonography exploration of patients in brain death. Transplant Proc 35 (2003), 1642–1643.
Cao, J., Watabe, D., Zhang, L., An EEG diagnosis system for quasi brain death based on complexity and energy analyses. Conf Proc IEEE Eng Med Biol Soc 2013 (2013), 7132–7135.
Cairns, H., Disturbances of consciousness with lesions of the brain-stem and diencephalon. Brain 75 (1952), 109–146.
Chang, J.J., Tsivgoulis, G., Katsanos, A.H., Malkoff, M.D., Alexandrov, A.V., Diagnostic accuracy of transcranial doppler for brain death confirmation: systematic review and meta-analysis. AJNR Am J Neuroradiol 37 (2016), 408–414.
Chatrian, G.E., White, L.E. Jr, Shaw, C.M., EEG pattern resembling wakefulness in unresponsive decerebrate state following traumatic brain-stem infarct. Electroencephalogr Clin Neurophysiol 16 (1964), 285–289.
Chaudhary, U., Birbaumer, N., Ramos-Murguialday, A., Brain-computer interfaces for communication and rehabilitation. Nat Rev Neurol 12 (2016), 513–525.
Citerio, G., Crippa, I.A., Bronco, A., Vargiolu, A., Smith, M., Variability in brain death determination in europe: looking for a solution. Neurocrit Care 21 (2014), 376–382.
Claassen, J., Velazquez, A., Meyers, E., Witsch, J., Falo, M.C., Park, S., et al. Bedside quantitative electroencephalography improves assessment of consciousness in comatose subarachnoid hemorrhage patients. Ann Neurol 80 (2016), 541–553.
Combaz, A., Chatelle, C., Robben, A., Vanhoof, G., Goeleven, A., Thijs, V., et al. A comparison of two spelling Brain-Computer Interfaces based on visual P3 and SSVEP in Locked-In Syndrome. PLoS One, 8, 2013, e73691.
Crone, J.S., Lutkenhoff, E.S., Bio, B.J., Laureys, S., Monti, M.M., Testing proposed neuronal models of effective connectivity within the cortico-basal ganglia-thalamo-cortical loop during loss of consciousness. Cereb Cortex 27 (2017), 2727–2738.
Cushing, H., Some experimental and clinical observations concerning states of increased intracranial tension. Am J Med Sci 124 (1902), 375–400.
Deliyannakis, E., Joannou, F., Davaroukas, A., Brain stem death with persistence of bioelectric activity of the cerebral hemispheres. Clin Electroenceph 6 (1975), 75–79.
Demertzi, A., Soddu, A., Laureys, S., Consciousness supporting networks. Curr Opin Neurobiol 23 (2013), 239–244.
Department of Health and Social Security Great Britain, The removal of cadaveric organs for transplantation: a code of practice. 1979, HMSO, London.
Doesburg, S.M., Ward, L.M., Corticothalamic necessity, qualia, and consciousness. Behav Brain Sci 30 (2007), 90–91.
Dringenberg, H.C., Olmstead, M.C., Integrated contributions of basal forebrain and thalamus to neocortical activation elicited by pedunculopontine tegmental stimulation in urethane-anesthetized rats. Neuroscience 119 (2003), 839–853.
Ducrocq, X., Hassler, W., Moritake, K., Newell, D.W., von Reutern, G.M., Shiogai, T., et al. Consensus opinion on diagnosis of cerebral circulatory arrest using Doppler-sonography: Task Force Group on cerebral death of the Neurosonology Research Group of the World Federation of Neurology. J Neurol Sci 159 (1998), 145–150.
Edelman, D.B., Consciousness without corticocentrism: Beating an evolutionary path. Behav Brain Sci 30 (2007), 91–92.
Escudero, D., Valentín, M.O., Escalante, J.L., Sanmartín, A., Perez-Basterrechea, M., de Gea, J., et al. Intensive care practices in brain death diagnosis and organ donation. Anaesthesia 70 (2015), 1130–1139.
Ferbert, A., Buchner, H., Ringelstein, E.B., Hacke, W., Der Hirnstammtod bei Basilaristhrombose - eine besondere Variante des Hirntodes?. Gänshirt, H., Berlit, B., Haack, G., (eds.) Verhandlungen der Deutschen Gesellschaft für Neurologie, Vol. 3, 1985, Springer, Berlin, 587–589.
Ferbert, A., Buchner, H., Ringelstein, E.B., Hacke, W., Isolated brain-stem death. Case report with demonstration of preserved visual evoked potentials (VEPs). Electroencephalogr Clin Neurophysiol 65 (1986), 157–160.
Ferbert, A., Buchner, H., Wulfinghoff, F., Korbmacher, G., Ringelstein, E.B., Hacke, W., Neurophysiological and neurosonological findings in isolated brain stem death. Kunze, K., Zangemeister, W.H., Arlt, A., (eds.) Clinical Problems of Brainstem Disorders, 1986, Thieme, Stuttgart, 141–144.
Ferbert, A., Buchner, H., Ringelstein, E.B., Hacke, W., Brain death from infratentorial lesions: clinical neurophysiological and transcranial Doppler ultrasound findings. Neurosurg Rev 12:Suppl. 1 (1989), 340–347.
Ferbert, A., Buchner, H., Brückmann, H., Brainstem auditory evoked potentials and somatosensory evoked potentials in pontine haemorrhage. Correlations with clinical and CT findings. Brain 113 (1990), 49–63.
Fernández-Torre, J.L., Hernández-Hernández, M.A., Muñoz-Esteban, C., Non confirmatory electroencephalography in patients meeting clinical criteria for brain death: scenario and impact on organ donation. Clin Neurophysiol 124 (2013), 2362–2367.
Fernández-Torre, J.L., López-Delgado, A., Hernández-Hernández, M.A., Paramio-Paz, A., Pía-Martínez, C., Orizaola, P., et al. Postanoxic alpha, theta or alpha-theta coma: Clinical setting and neurological outcome. Resuscitation 124 (2018), 118–125.
Fischer, D.B., Boes, A.D., Demertzi, A., Evrard, H.C., Laureys, S., Edlow, B.L., et al. A human brain network derived from coma-causing brainstem lesions. Neurology 87 (2016), 2427–2434.
Flowers, W.M. Jr, Patel, B.R., Persistence of cerebral blood flow after brain death. South Med J 93 (2000), 364–370.
Friedenberg, D.A., Bouton, C.E., Annetta, N.V., Skomrock, N., Zhang, Mingming, Schwemmer, M., et al. Big data challenges in decoding cortical activity in a human with quadriplegia to inform a brain computer interface. Conf Proc IEEE Eng Med Biol Soc, 2016, 2016, 3084–3087.
Frowein, R.A., Gänshirt, H., Richard, K.E., Hamel, E., Haupt, W.F., Kriterien des Hirntodes: 3. Generation. Erläuterung zur Fortschreibung der von der Bundesärztekammer gegebenen Entscheidungshilfen zur Feststellung des Hirntodes. Anasth Intensivther Notfallmed 22 (1987), 17–20.
Fuller, P.M., Sherman, D., Pedersen, N.P., Saper, C.B., Lu, J., Reassessment of the structural basis of the ascending arousal system. J Comp Neurol 519 (2011), 933–956.
Garrett, M.P., Williamson, R.W., Bohl, M.A., Bird, C.R., Theodore, N., Computed tomography angiography as a confirmatory test for the diagnosis of brain death. J Neurosurg 128 (2018), 639–644.
Giacino, J.T., Fins, J.J., Laureys, S., Schiff, N.D., Disorders of consciousness after acquired brain injury: the state of the science. Nat Rev Neurol 10 (2014), 99–114.
Gosseries, O., Di, H., Laureys, S., Boly, M., Measuring consciousness in severely damaged brains. Annu Rev Neurosci 37 (2014), 457–478.
Grigg, M.M., Kelly, M.A., Celesia, G.G., Ghobrial, M.W., Ross, E.R., Electroencephalographic activity after brain death. Arch Neurol 44 (1987), 948–954.
Guenther, F.H., Brumberg, J.S., Brain-machine interfaces for real-time speech synthesis. Conf Proc IEEE Eng Med Biol Soc 2011 (2011), 5360–5363.
Gütling, E., Isenmann, S., Wichmann, W., Electrophysiology in the locked-in-syndrome. Neurology 46 (1996), 1092–1101.
Haupt, W.F., Rudolf, J., European brain death codes: a comparison of national guidelines. J Neurol 246 (1999), 432–437.
Hawkes, C.H., Bryan-Smyth, L., The electroencephalogram in the “locked-in” syndrome. Neurology 24 (1974), 1015–1018.
Hayashi, R., Hanyu, N., Yanagisawa, N., Alpha-pattern coma in primary brainstem hemorrhage; clinical, electrophysiologic, and cerebral blood flow studies. Intern Med 35 (1996), 905–908.
Heckmann, J.G., Lang, C.J., Pfau, M., Neundörfer, B., Electrocerebral silence with preserved but reduced cortical brain perfusion. Eur J Emerg Med 10 (2003), 241–243.
Heywood, P., Murphy, K., Corfield, D.R., Morrell, M.J., Howard, R.S., Guz, A., Control of breathing in man; insights from the 'locked-in' syndrome. Respir Physiol 106 (1996), 13–20.
Hofmeijer, J., van Putten, M.J.A.M., EEG in postanoxic coma: Prognostic and diagnostic value. Clin Neurophysiol 127 (2016), 2047–2055.
Horn-Bochtler, A.K.E., Büttner-Ennever, J.A., Neuroanatomy of the brainstem. Urban, P., Caplan, L.R., (eds.) Brainstem Disorders, 2011, Springer, Berlin Heidelberg, 1–36.
Hughes, S.W., Crunelli, V., Thalamic mechanisms of EEG alpha rhythms and their pathological implications. Neuroscientist 11 (2005), 357–372.
Ikeda, K., Kawakami, K., Onimaru, H., Okada, Y., Yokota, S., Koshiya, N., et al. The respiratory control mechanisms in the brainstem and spinal cord: integrative views of the neuroanatomy and neurophysiology. J Physiol Sci 67 (2017), 45–62.
Jacome, D.E., Morilla-Pastor, D., Unreactive EEG: pattern in locked-in syndrome. Clin Electroencephalogr 21 (1990), 31–36.
Jennett, B., Gleave, J., Wilson, P., Brain death in three neurosurgical units. Br Med J (Clin Res Ed) 282 (1981), 533–539.
Jørgensen, E.O., EEG without detectable cortical activity and cranial nerve areflexia as parameters of brain death. Electroencephalogr Clin Neurophysiol 36 (1974), 70–75.
Jørgensen, E.O., Brain death: retrospective surveys. Lancet 317 (1981), 378–379.
Jørgensen, E.O., Malchow-Møller, A., Natural history of global and critical brain ischemia. Part I: EEG and neurological signs during the first year after cardiopulmonary resuscitation in patients subsequently regaining consciousness. Resuscitation 9 (1981), 133–153.
Kahn, P.A., Bioethics, Religion, and Public Policy: Intersections, Interactions, and Solutions. J Relig Health 55 (2016), 1546–1560.
Kaukinen, S., Mäkelä, K., Häkkinen, V.K., Martikainen, K., Significance of electrical brain activity in brain-stem death. Intensive Care Med 21 (1995), 76–78.
Kirschstein, T., Köhling, R., What is the source of the EEG?. Clin EEG Neurosci 40 (2009), 146–149.
Koch, C., Massimini, M., Boly, M., Tononi, G., Neural correlates of consciousness: progress and problems. Nat Rev Neurosci 17 (2016), 307–321.
Kotagal, S., Rolfe, U., Schwarz, K.B., Escober, W., “Locked-in” state following Reye's syndrome. Ann Neurol 15 (1984), 599–601.
Kuwabara, S., Ohta, K., Ueda, T., Yamane, K., Uemura, Y., Takahashi, M., Clinical study of 20 cases of primary pontine hemorrhage. With special reference to correlations between clinical, computed tomographic, and electroencephalographic findings and outcome. Neurol Med Chir (Tokyo) 22 (1982), 933–942.
Laureys, S., Science and society: death, unconsciousness and the brain. Nat Rev Neurosci 6 (2005), 899–909.
Laureys, S., The neural correlate of (un)awareness: lessons from the vegetative state. Trends Cogn Sci 9 (2005), 556–559.
Laureys, S., Pellas, F., Van Eeckhout, P., Ghorbel, S., Schnakers, C., Perrin, F., et al. The locked-in syndrome: what is it like to be conscious but paralyzed and voiceless?. Prog Brain Res 150 (2005), 495–511.
Laureys, S., Fins, J.J., Are we equal in death? Avoiding diagnostic error in brain death. Neurology 70 (2008), e14–e15.
Lee, P., Total brain death and the integration of the body required of a human Being. J Med Philos 41 (2016), 300–314.
Lesenfants, D., Habbal, D., Lugo, Z., Lebeau, M., Horki, P., Amico, E., et al. An independent SSVEP-based brain-computer interface in locked-in syndrome. J Neural Eng, 11, 2014, 035002.
Lesenfants, D., Habbal, D., Chatelle, C., Soddu, A., Laureys, S., Noirhomme, Q., Toward an attention-based diagnostic tool for patients with locked-in syndrome. Clin EEG Neurosci 49 (2018), 122–135.
Linse, K., Rüger, W., Joos, M., Schmitz-Peiffer, H., Storch, A., Hermann, A., Eye-tracking-based assessment suggests preserved well-being in locked-in patients. Ann Neurol 81 (2017), 310–315.
Lindsley, D.B., Bowden, J., Magoun, H.W., Effect upon the EEG of acute injury to the brain stem activating system. Electroencephalogr Clin Neurophysiol 1 (1949), 475–486.
Loeb, C., Electroencephalographic changes during the state of coma. Electroencephalogr Clin Neurophysiol 10 (1958), 589–606.
Loeb, C., Poggio, G., Electroencephalograms in a case with ponto-mesencephalic haemorrhage. Electroencephalogr Clin Neurophysiol 5:Suppl. (1953), 295–296.
Lopes da Silva, F.H., Vos, J.E., Mooibroek, J., Van Rotterdam, A., Relative contributions of intracortical and thalamo-cortical processes in the generation of alpha rhythms, revealed by partial coherence analysis. Electroencephalogr Clin Neurophysiol 50 (1980), 449–456.
López-Navidad, A., Chronic, “brain death”: meta-analysis and conceptual consequences. Neurology, 53, 1999, 1369.
Lugo, Z.R., Rodriguez, J., Lechner, A., Ortner, R., Gantner, I.S., Laureys, S., et al. A vibrotactile p300-based brain-computer interface for consciousness detection and communication. Clin EEG Neurosci 45 (2014), 14–21.
Lulé, D., Zickler, C., Häcker, S., Bruno, M.A., Demertzi, A., Pellas, F., et al. Life can be worth living in locked-in syndrome. Prog Brain Res 177 (2009), 339–351.
Lulé, D., Noirhomme, Q., Kleih, S.C., Chatelle, C., Halder, S., Demertzi, A., et al. Probing command following in patients with disorders of consciousness using a brain-computer interface. Clin Neurophysiol 124 (2013), 101–106.
Lundervold, A., Hauge, T., Löken, A.C., Unusual EEG in unconscious patient with brain stem atrophy. Electroencephalogr Clin Neurophysiol 8 (1956), 665–670.
Magnin, M., Rey, M., Bastuji, H., Guillemant, P., Mauguière, F., Garcia-Larrea, L., Thalamic deactivation at sleep onset precedes that of the cerebral cortex in humans. Proc Natl Acad Sci USA 107 (2010), 3829–3833.
Martelli, D., Stanić, D., Dutschmann, M., The emerging role of the parabrachial complex in the generation of wakefulness drive and its implication for respiratory control. Respir Physiol Neurobiol 188 (2013), 318–323.
Medlock, M.D., Hanigan, W.C., Cruse, R.P., Dissociation of cerebral blood flow, glucose metabolism, and electrical activity in pediatric brain death. Case report. J Neurosurg 79 (1993), 752–755.
Meienberg, O., Mumenthaler, M., Karbowski, K., Quadriparesis and nuclear oculomotor palsy with total bilateral ptosis mimicking coma: a mesencephalic 'locked-in syndrome“?. Arch Neurol 36 (1979), 708–710.
Merker, B., Consciousness without a cerebral cortex: a challenge for neuroscience and medicine. Behav Brain Sci 30 (2007), 63–81.
Misis, M., Gener Raxach, J., Perez Molto, H., Martinez Vega, S., Sanchez, Rico P., Bispectral index monitoring for early detection of brain death. Transpl Proc 40 (2008), 1279–1281.
Mohandas, A., Chou, S.N., Brain death. A clinical and pathological study. J Neurosurg 35 (1971), 211–218.
Mollaret, P., Bertrand, I., Mollaret, H., Coma dépassé et nécroses nerveuses centrales massives. Rev Neurol (Paris) 101 (1959), 116–139.
Moschella, M., Deconstructing the brain disconnection-brain death analogy and clarifying the rationale for the neurological criterion of death. J Med Philos 41 (2016), 279–299.
Moruzzi, G., Magoun, H., Brain stem reticular formation and activation of the EEG. Electroencephalogr Clin Neurophysiol 1 (1949), 455–473.
Naccache, L., Minimally conscious state or cortically mediated state?. Brain 141 (2018), 949–960.
Norton, L., Gibson, R.M., Gofton, T., Benson, C., Dhanani, S., Shemie, S.D., et al. Electroencephalographic recordings during withdrawal of life-sustaining therapy until 30 minutes after declaration of death. Can J Neurol Sci 44 (2017), 139–145.
Obeso, J.A., Iragui, M.I., Marti-Masso, J.F., Maravi, E., Teijeira, J.M., Carrera, N., et al. Neurophysiological assessment of alpha pattern coma. J Neurol Neurosurg Psychiatry 43 (1980), 63–67.
Pallis, C., ABC of brain stem death. From brain death to brain stem death. Br Med J (Clin Res Ed) 285 (1982), 1487–1490.
Pallis, C., Danish ethics council rejects brain death as the criterion of death – commentary 2: return to Elsinore. J Med Ethics 16 (1990), 10–13.
Pana, R., Hornby, L., Shemie, S.D., Dhanani, S., Teitelbaum, J., Time to loss of brain function and activity during circulatory arrest. J Crit Care 34 (2016), 77–83.
Parvizi, J., Damasio, A.R., Neuroanatomical correlates of brainstem coma. Brain 126 (2003), 1524–1536.
Posner, J.B., Saper, C.B., Schiff, N.D., Plum, F., Plum and Posner's diagnosis of stupor and coma. 4th ed., 2007, Oxford University Press, Oxford, New York.
Quesnel, C., Fulgencio, J.P., Adrie, C., Marro, B., Payen, L., Lembert, N., et al. Limitations of computed tomographic angiography in the diagnosis of brain death. Intensive Care Med 33 (2007), 2129–2135.
Rady, M.Y., Verheijde, J.L., Legislative enforcement of nonconsensual determination of neurological (brain) death in muslim patients: a violation of religious rights. J Relig Health 57 (2018), 649–661.
Reilly, E.L., Electrocerebral inactivity as a temperature effect: unlikely as an isolated etiology. Clin Electroencephalogr 12 (1981), 69–71.
Rodin, E., Tahir, S., Austin, D., Andaya, L., Brainstem death. Clin Electroencephalogr 16 (1985), 63–71.
Roth, C., Ferbert, A., Aneurysmatische Subarachnoidalblutung und Entwicklung eines, isolierten Hirnstammtods“. Fortschr Neurol Psychiatr 84 (2016), 377–384.
Sakai, K., el Mansari, M., Jouvet, M., Inhibition by carbachol microinjections of presumptive cholinergic PGO-on neurons in freely moving cats. Brain Res 527 (1990), 213–223.
Sarasso, S., Rosanova, M., Casali, A.G., Casarotto, S., Fecchio, M., Boly, M., et al. Quantifying cortical EEG responses to TMS in (un)consciousness. Clin EEG Neurosci 45 (2014), 40–49.
Schnakers, C., Perrin, F., Schabus, M., Hustinx, R., Majerus, S., Moonen, G., et al. Detecting consciousness in a total locked-in syndrome: an active event-related paradigm. Neurocase 15 (2009), 271–277.
Sellers, E.W., Ryan, D.B., Hauser, C.K., Noninvasive brain-computer interface enables communication after brainstem stroke. Sci Transl Med, 6, 2014, 257re7.
Shemie, S.D., Hornby, L., Baker, A., Teitelbaum, J., Torrance, S., Young, K., et al. International guideline development for the determination of death. Intensive Care Med 40 (2014), 788–797.
Shewmon, D.A., Chronic “brain death”: meta-analysis and conceptual consequences. Neurology 51 (1998), 1538–1545.
Shewmon, D.A., Constructing the death elephant: a synthetic paradigm shift for the definition, criteria, and tests for death. J Med Philos 35 (2010), 256–298.
Shewmon, D.A., Holmes, G.L., Byrne, P.A., Consciousness in congenitally decorticate children: developmental vegetative state as self-fulfilling prophecy. Dev Med Child Neurol 41 (1999), 364–374.
Solms, M., What is “the unconscious,” and where is it located in the brain? A neuropsychoanalytic perspective. Ann NY Acad Sci 1406 (2017), 90–97.
Stecker, M.M., Sabau, D., Sullivan, L., Das, R.R., Selioutski, O., Drislane, F.W., et al. American clinical neurophysiology society guideline 6: minimum technical standards for EEG recording in suspected cerebral death. J Clin Neurophysiol 33 (2016), 324–327.
Stender, J., Gosseries, O., Bruno, M.A., Charland-Verville, V., Vanhaudenhuyse, A., Demertzi, A., et al. Diagnostic precision of PET imaging and functional MRI in disorders of consciousness: a clinical validation study. Lancet 384 (2014), 514–522.
Steriade, M., Gloor, P., Llinás, R.R., Lopes de Silva, F.H., Mesulam, M.M., Report of IFCN committee on basic mechanisms. basic mechanisms of cerebral rhythmic activities. Electroencephalogr Clin Neurophysiol 76 (1990), 481–508.
Steriade, M., The corticothalamic system in sleep. Front Biosci 8 (2003), d878–d899.
Steudel, W.I., Krüger, J., Grau, H., Zur Alpha- und Spindel-Aktivität bei komatösen Patienten nach einer Schädel-Hirn-Verletzung unter besonderer Berücksichtigung der Computertomographie. EEG EMG Z Elektroenzephalogr Elektromyogr Verwandte Geb 10 (1979), 143–147.
Synek, V.M., EEG abnormality grades and subdivisions of prognostic importance in traumatic and anoxic coma in adults. Clin Electroencephalogr 19 (1988), 160–166.
Szurhaj, W., Lamblin, M.D., Kaminska, A., Sediri, H., Société de Neurophysiologie Clinique de Langue Française. EEG guidelines in the diagnosis of brain death. Neurophysiol Clin 45 (2015), 97–104.
Tatum, W.O., Dworetzky, B.A., Freeman, W.D., Schomer, D.L., Artifact: recording EEG in special care units. J Clin Neurophysiol 28 (2011), 264–277.
Taylor, T., Dineen, R.A., Gardiner, D.C., Buss, C.H., Howatson, A., Pace, N.L., Computed tomography (CT) angiography for confirmation of the clinical diagnosis of brain death. Cochrane Database Syst Rev, 3, 2014, CD009694.
Thibaut, A., Bruno, M.A., Chatelle, C., Gosseries, O., Vanhaudenhuyse, A., Demertzi, A., et al. Metabolic activity in external and internal awareness networks in severely brain-damaged patients. J Rehabil Med 44 (2012), 487–494.
Ueyama, T., Shirataki, K., Tamaki, N., Traumatic basilar artery dissection presenting with “locked-in” syndrome: report of a case. No Shinkei Geka 24 (1996), 1035–1039.
Uldry, P.A., Despland, P.A., Regli, F., Alpha-coma: présentation rétrospective de 20 cas. Neurophysiol Clin 21 (1991), 85–94.
van der Hoeven, J.A., Molema, G., Ter Horst, G.J., Freund, R.L., Wiersema, J., van Schilfgaarde, R., et al. Relationship between duration of brain death and hemodynamic (in)stability on progressive dysfunction and increased immunologic activation of donor kidneys. Kidney Int 64 (2003), 1874–1882.
van Dijk, J.G., Testing brain death: a trying condition. Clin Neurophysiol 124 (2013), 2286–2287.
Vanhaudenhuyse, A., Noirhomme, Q., Tshibanda, L.J., Bruno, M.A., Boveroux, P., Schnakers, C., et al. Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients. Brain 133 (2010), 161–171.
Varelas, P.N., Brainstem or entire brain-based declaration of death: is there a difference?. Pract Neurol 16 (2016), 85–86.
Venizelos, A.P., Bleck, T.P., Alpha-frequency EEG artifact from a high-frequency oscillatory ventilator (HFOV). Clin Neurophysiol, 124, 2013, 1258.
Vicenzini, E., Pro, S., Randi, F., Pulitano, P., Spadetta, G., Rocco, M., et al. Transcranial Doppler for brain death after decompressive craniectomy: persistence of cerebral blood flow with flat EEG. Intensive Care Med 36 (2010), 2163–2164.
Vignaendra, V., Wilkus, R.J., Copass, M.K., Chatrian, G.E., Electroencephalographic rhythms of alpha frequency in comatose patients after cardiopulmonary arrest. Neurology 24 (1974), 582–588.
Wagner, W., Ungersböck, K., Perneczky, A., Preserved cortical somatosensory evoked potentials in apnoeic coma with loss of brain-stem reflexes: case report. J Neurol 240 (1993), 243–248.
Wahlster, S., Wijdicks, E.F., Patel, P.V., Greer, D.M., Hemphill, J.C. 3rd, Carone, M., et al. Brain death declaration: Practices and perceptions worldwide. Neurology 84 (2015), 1870–1879.
Walker, A.E., Diamond, E.L., Moseley, J., The neuropathological findings in irreversible coma. A critique of the “respirator brain”. J Neuropathol Exp Neurol 34 (1975), 295–323.
Walter, U., Brandt, S.A., Ferbert, A., Förderreuther, S., Hansen, H.C., Hinrichs, H., et al. Empfehlungen der Deutschen Gesellschaft für Klinische Neurophysiologie und Funktionelle Bildgebung zur Diagnostik des irreversiblen Hirnfunktionsausfalls. Klin Neurophysiol 47 (2016), 16–20.
Walter, U., Schreiber, S.J., Kaps, M., Doppler and Duplex Sonography for the Diagnosis of the Irreversible Cessation of Brain Function (“Brain Death”): Current Guidelines in Germany and Neighboring Countries. Ultraschall Med 37 (2016), 558–578.
Walter, U., Noachtar, S., Hinrichs, H., Digitale Elektroenzephalographie in der Hirntoddiagnostik. Technische Anforderungen und Ergebnisse einer Umfrage zur Richtlinienkompatibilität digitaler EEG-Systeme bei Anbietern in Deutschland. Nervenarzt 89 (2018), 156–162.
Wee, A.S., Scalp EMG in brain death electroencephalogram. Acta Neurol Scand 74 (1986), 128–131.
Welschehold, S., Boor, S., Reuland, K., Thömke, F., Kerz, T., Reuland, A., et al. Technical aids in the diagnosis of brain death: a comparison of SEP, AEP, EEG, TCD and CT angiography. Dtsch Arztebl Int 109 (2012), 624–630.
Welschehold, S., Kerz, T., Boor, S., Reuland, K., Thömke, F., Reuland, A., et al. Detection of intracranial circulatory arrest in brain death using cranial CT-angiography. Eur J Neurol 20 (2013), 173–179.
Wertheimer, P., Jouvet, M., Descotes, J., Á propos du diagnostic de la mort du système nerveux dans les comas avec arrêt respiratoire traités par respiration artificielle. Presse Med 67 (1959), 87–88.
Westmoreland, B.F., Klass, D.W., Sharbrough, F.W., Reagan, T.J., Alpha-coma. Electroencephalographic, clinical, pathologic, and etiologic correlations. Arch Neurol 32 (1975), 713–718.
Wijdicks, E.F., Determining brain death in adults. Neurology 45 (1995), 1003–1011.
Wijdicks, E.F., The case against confirmatory tests for determining brain death in adults. Neurology 75 (2010), 77–83.
Wijdicks, E.F., The transatlantic divide over brain death determination and the debate. Brain 135 (2012), 1321–1331.
Wijdicks, E.F., Scott, J.P., Outcome in patients with acute basilar artery occlusion requiring mechanical ventilation. Stroke 27 (1996), 1301–1303.
Wijdicks, E.F., Pfeifer, E.A., Neuropathology of brain death in the modern transplant era. Neurology 70 (2008), 1234–1237.
Wijdicks, E.F., Varelas, P.N., Gronseth, G.S., Greer, D.M., American Academy of Neurology. Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 74 (2010), 1911–1918.
Wilkus, R.J., Harvey, F., Ojemann, L.M., Lettich, E., Electroencephalogram and sensory evoked potentials. Findings in an unresponsive patient with pontine infarct. Arch Neurol 24 (1971), 538–544.
Yoshioka, T., Sugimoto, H., Uenishi, M., Sakamoto, T., Sadamitsu, D., Sakano, T., et al. Prolonged hemodynamic maintenance by the combined administration of vasopressin and epinephrine in brain death: a clinical study. Neurosurgery 18 (1986), 565–567.
Young, G.B., Lee, D., A critique of ancillary tests for brain death. Neurocrit Care 1 (2004), 499–508.
Zec, N., Kinney, H.C., Anatomic relationships of the human nucleus paragigantocellularis lateralis: a DiI labeling study. Auton Neurosci 89 (2001), 110–124.
Zwarts, M.J., Kornips, F.H., Vogels, O.M., Clinical brainstem death with preserved electroencephalographic activity and visual evoked response. Arch Neurol, 58, 2001, 1010.