medigraphic.com
Academia Mexicana de Neurología, A.C.

2005, Number 4

<< Back Next >>

Rev Mex Neuroci 2005; 6 (4)

Encephalic death: physiopathology and neuropathology

Escobar A

Language: Spanish
References: 54
Page: 327-335
PDF size: 71.22 Kb.


ABSTRACT

Brain death is at present the accepted criterion to establish the diagnosis of death in all medical aspects and in public opinion. It implies the irreversible destruction of the brain with associated loss of spontaneous breathing and persistent cardiac rhythm. Brain death forms the basis of the Uniform Death Determination Act. Brain death may follow head trauma, subarachnoid hemorrhage, child abuse or chocking. In 1959, the concept of coma depassé (irreversible coma) was introduced based on 23 cases with loss of consciousness, of brain stem reflexes, spontaneous breathing, isoelectric EEG, and massive necrosis of the brain, all of which led to define the concept of irreversible coma as brain death. Due to clinical similarities the locked-in syndrome, Guillain-Barré-Strohl peripheral neuropathy, accidental hypothermia, alcoholic intoxication, overdose of anesthetics, barbiturates, addictive drugs, antidepressants, and trauma must be considered in the differential diagnoses prior to diagnosis of brain death. The brain energetic requirements to maintain normal function depend on the constant flow of oxygen and glucose. Blood flow, blood perfusion pressure, intracranial pressure, blood viscosity, vascular resistance, and capillary density, are also participant factors. In cardiac arrest the oxygen drops to zero level with ensuing global brain death. Oxygen deficit in atmospheric air leading to hypoxia, induces brain lesions of varied topography obeying level of neuronal activity, intensity and duration of the hypoxia. Brain areas susceptible to oxygen and glucose deficits include the hippocampal pyramidal layer, neocortical layers3, 4, 5, cerebellar Purkinje and granular layers, Globus pallidus, and subcortical white matter. The peculiar susceptibility of brain areas to damage by hypoxia is based on the theory of pathoclisis or selective” topistic” vulnerability. Neuronal necrosis in ischemic hypoxia is due to glutamate excitotoxicity acting upon NMDA, AMPA, kainate and metabotropic receptors. Besides neuronal necrosis, programmed cell death also occurs, it is a morphological change named apoptosis. It occurs in sequential stages beginning by cell shrinkage, nuclear chromatin condensation and fragmentation, cytoplasm surface blebbing and extrusion of membrane bound apoptotic bodies. Cascading molecular events to apoptosis include signaling pathways to initiate apoptosis, control and integration, a common-execution phase, and removal of dead cells by phagocytosis. Mitochondrial permeability to release cytochrome c an apoptotic trigger into the cytosol, and gene participation ensue. Bcl-2, Bax, Bad, BclX, Apaf-1, p53; all are genes encoding proteins that may exert pro-apoptotic or anti-apoptotic actions. Conclusion: In clinical practice, in order to avoid any doubts, confirmatory laboratory tests are required as proof of the clinical diagnosis of brain death, which once firmly established leads to declare that the patient is dead, followed by unplugging mechanical ventilation. All of this must be in agreement with the bioethical, legal, and religious regulations and family consent.


REFERENCES

  1. Uniform Determination of Death Act, 12 Uniform Laws Annotated (U.L.A.) 589 (West 1993 and West Supp. 1997) (Quoted by Wijdicks, Ref. 9)

  2. Mollaret P, Goulon M. Le coma dépasse. (Memoire preliminaire) Revue Neurologique 1959; 101: 3-15

  3. Mollaret P, Bertrand I, Mollaret H. Coma dépasse et nécroses nerveuses centrales massives. Revue Neurologique 1959; 101: 116-39.

  4. A definition of irreversible coma: report of the Ad Hoc Committee of the Harvard Medical School to examine the definition of brain death. JAMA 1968; 205: 337-40.

  5. Conference of Royal Colleges and Faculties of the United Kingdom: diagnosis of brain death. Lancet 1976; 2: 1069-70.

  6. Mohandas A, Chou SN. Brain death: a clinical and pathological study. J Neurosurg 1971; 35: 211-8.

  7. Black PMcL. Brain death. NEJM (First of two parts) 1978; 299: 338.44. (second of two parts) 299: 393-401.

  8. Guidelines for the determination of death: report of the Medical Consultants on the Diagnosis of Death to the President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. JAMA 1981; 246: 2184-6.

  9. Wijdicks EFM. The diagnosis of brain death. NEJM 2001; 344: 1215-46.

  10. Wijdicks EFM. Determining brain death in adults. Neurology 1995; 45: 1003-11.

  11. Patterson JR, Grabois M. Locked-in syndrome: a review of 139 cases. Stroke 1986; 17: 758-64.

  12. Kotsoris H, et al. Total locked-in state resembling brain death in polyneuropathy. Ann Neurol 1984; 16: 150 (abstract).

  13. Danzl DE, Pozos RS. Accidental hypothermia. NEJM 1994; 331: 1756-60.

  14. Gilbert M, et al. Resuscitation from accidental hypothermia of 13.7 °C with circulatory arrest. Lancet 2000; 355: 375-6.

  15. Yang KL, Dantzker DR. Reversible brain death: a manifestation of amitriptyline overdose. Chest 1991; 99: 1037-8.

  16. Graham DI, et al. Trauma. In: DI Graham, PL Lantos (Eds.). Greenfield’s Neuropathology. 7th Ed. Vol. I, Chapt. 14. Arnold, London: 2002, p. 823-98.

  17. Auer RN, Sutherland GR. Hypoxia and related conditions. In: DI Graham, PL Lantos (Eds.). Greenfield’s Neuropathology. 7th Edition. Vol. I. Chapt 5. Arnold, London: 2002; p. 233-80.

  18. Vogt C, Vogt O. Erkrankungen der Grosshirnrinde im Lichte der Topistik, Pathoklise, und Pathoarchitetonik. J Psychol Neurol 1922; 28: 1-171 (Citado en Ref. 17).

  19. Escobar A, Nieto D. Anoxia cerebral. Consideraciones sobre la patogenia y la topografía de las lesiones. Neurol Neurocir Psiquiat (México) 1963; 4: 57-63.

  20. Escobar A, Sáenz-Arroyo L. Degeneración de la capa granular del cerebelo. Estudio de dos casos. Bol Inst Estud Méd Biól Méx 1960; 18: 105-22.

  21. Benveniste H, et al. Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem 1984; 43: 1369-74.

  22. Plum F, Posner JB, Hain RF. Delayed neurological deterioration after anoxia. Arch Int Med 1962; 110: 56-63.

  23. Craigie EH. On the relative vascularity of various parts of the central nervous system of the albino rat. J Comp Neurol 1920; 31: 429-64.

  24. Guyton AC, Hall JE. Textbook of Medical Physiology. 10th Ed. Chapt 61. Philadelphia: Saunders; 2000, p. 709-15 (Cerebral blood flow; the cerebro spinal fluid; and brain metabolism).

  25. Guyton AC, Hall JE. Textbook of Medical Physiology. 10th Ed. Chapt. 37. Philadelphia: Saunders; 2000, p. 432-43 (Pulmonary ventilation).

  26. Purpura V, et al. Glutamate-mediated astrocyte-neuron signaling. Nature 1994; 369: 744-7.

  27. MacVicar VA, et al. GABA activated Cl- channels in astrocytes of hippocampal slices. J Neurosci 1989; 9: 3577-83.

  28. Bertrand I, et al. Nécroses massives du systéme nerveux central dans une survie artificielle. Revue Neurologique 1959; 101: 101-15.

  29. Smith AJK, Penry JK. Brain death: a bibliography with key-word and author indexes. (DHEW Publication No. [NIH] 73-347). Washington, D.C. Government Printing Office, 1972.

  30. Smith AJK, Walker AE. Cerebral blood flow and brain metabolism as indicators of cerebral death: a review. Johns Hopkins Med J 1973; 133: 107-19.

  31. Kjeldsberg CR. Respirator brain. In: J Minckler (Ed.). Pathology of the Nervous System. Vol. 3. Chapt. 211. New York: McGraw-Hill; 1972, p. 2952-961.

  32. An appraisal of the criteria of cerebral death: a summary statement: a collaborative study. JAMA 1976; 237: 982-6.

  33. Walker AE, et al. The neuropathological findings in irreversible coma: a critique of the “respirator brain”. J Neuropathol Exper Neurol 1975; 34: 295-323.

  34. Adams RD, Jéquier M. The brain death syndrome: hypoxemic panencephalopathy. Schweiz Med Wochenschr 1969; 99: 65-73.

  35. Riishede J, Ethelberg S. Angiographic changes in sudden and severe herniation of brain stem through tentorial incisure: report of five cases. Arch Neurol Psychiat 1953; 70: 399-409.

  36. Bradac GB, Simon RS. Angiography in brain death. Neuroradiology 1974; 7: 25. In: American EEG Society. Guideline three: minimum technical standards for EEG recording in suspected cerebral death. J Clin Neurophysiol 1994; 11: 10-3.

  37. Auer RN, et al. The temporal evolution of hypoglycemic bran damage. I. Light and electron microscopic findings in the rat cerebral cortex. Acta Neuropathol (Berl) 1985; 67: 13-24.

  38. Olney JW. Glutamate-induced neuronal necrosis in the infant mouse hypothalamus J Neuropath Exper Neurol 1971; 30: 75-90.

  39. Nakanishi S. Molecular diversity of glutamate receptors and implications for brain function. Science 1992; 258: 597-603.

  40. Graeber MB, et al. Cellular pathology of the central nervous system. In: Graham DI, Lantos PL (Eds.). Greenfield’s Neuropathology, 7th Ed. Chapt. 3. London: Arnold; p. 123-91.

  41. Lodish H, et al. Cell birth, lineage, and death. In: Lodish H, et al. Molecular Cell Biology. 5th Ed. Chapt. 22. New York: Freeman; 2004, p. 899-934.

  42. Pollard TD, Earnshaw WC. Programmed cell death. In: Pollard TD, Earnshaw WC. Cell Biology. Chapt 49. Philadelphia: Saunders; 2002, p. 767-82.

  43. Kaufmann SH, Hengartner MO. Programmed cell death: alive and well in the new millennium. Trends Cell Biol 2001; 11: 526-34.

  44. Wyllie AH, et al. The significance of apoptosis. Int Rev Cytol 1980; 68: 251-5.

  45. Nagata S. Apoptosis by death factor. Cell 1997; 88: 355-65.

  46. Antonsson B, Martinou JC. The Bcl-2 protein family. Exp Cell Res 2000; 256: 50-7.

  47. Vaux DL, Korsmeyer SJ. Cell death in development. Cell 1999; 96: 245-54.

  48. Cheng EH, et al. BCL-2, BCLX(L) sequester BH3 domain-only molecules preventing BAX- BAK- mediated mitochondrial apoptosis. Mol Cell 2001; 8: 705-11.

  49. Earnshaw WC, et al. Mammalian caspases: Structure, activation, substrates and functions during apoptosis. Ann Rev Biochem 1999; 68: 383-424.

  50. Penninger JM, Kroemer G. Mitochondria, AIF and caspases – rivaling for cell death execution. Nature Cell Biol 2003; 5: 97-9.

  51. Cotran RS, Kumar V, Collins T. Robbins pathologic basis of disease. 6th Ed. Philadelphia: Saunders; 1999, p. 1-29 (Cellular pathology I: Cell injury and cell death).

  52. Perry GW, et al. The role of transcranial Doppler in confirming brain death: sensitivity, specificity and suggestions for performance and interpretation. Neurology 1990; 40: 300-3.

  53. Bonetti MG, et al. 99m Tc Hm-PAO brain perfusion SPECT in brain death. Neuroradiology 1995; 37: 365-9.

  54. Walker AE, Mollinari GF. Criteria of cerebral death. Trans Amer Neurol Assoc 1975; 100: 29-35.




2020     |     www.medigraphic.com