Diffuse Axonal Injury after Head Trauma. A Review
Traumatic brain injury is a major health problem in all developed countries. Because of the long-term disabilities suffered by head-injured patients, such injuries are a continuous organizational challenge for health systems and a burden for community and
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SAHUQUILLO
and M. A.
POCA
Department of Neurosurgery, Vall d'Hebron University Hospital, Barcelona, Spain With 19 Figures
Contents Introduction... ..... ..... ...... ....... .................. ....... .......... ..... Fundamental Structure and Function of the Central Nervous System Axon The Axonal Membrane (Axolemma)........................................ Microtubules and Neurofilaments. The Neuronal Cytoskeleton............ Axonal Transport and its Mechanisms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Calcium and Calcium-Dependent Breakdown of Neurofilaments .......... Physiopathology of Head Injury. Diffuse Versus Focal Injuries............ Post-Traumatic Cellular Events and the Concept of Traumatic Penumbra Classical Definition of Traumatic Diffuse Axonal Injury.. . . . . . . . . . . . . . . . . . Biomechanics of Diffuse Axonal Injury. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Characteristics of Mechanical Loading...... .. ........................... The Centripetal Theory of Ommaya...................................... The Centripetal Theory and the Concept of Primary Brainstem Injury. . . . The Reticular Formation and the Primary Brainstem Damage Saga...... Clinical and Experimental Validation of the Centripetal Theory........... The Neuropathological Spectrum of DAr. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Focal Lesions Observed in the Brain in DAI............................. Pathogenesis of the Corpus Callosum Hemorrhages. . . . . . . . . . . . . . . . . . . . . Neuropathological Grading of DAI. . . . . . . . . . . . . . . . . .. . . . . . . . . . .. . .. . . . . . . . . Axonal Retraction Balls, Microglial Stars and Wallerian Degeneration... Axonal Retraction Balls.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Microglial Clusters (Microglial Stars) .................................... Wallerian Degeneration... .. ..... ..... ....... ....... .............. ... ..... Experimental Models of DAI ............................................... Marmarou's Rodent Model of DAI .. ....... ..................... ........ Changing Concepts in Diffuse Axonal Injury. Is DAI Always a Primary Lesion?...................................................................... Experimental Evidence of Secondary Axotomy in Closed Head Injuries .. Pathogenesis of Diffuse Axonal Injury. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . J. D. Pickard et al. (eds.), Advances and Technical Standards in Neurosurgery © Springer-Verlag/Wien 2002
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J. SAHUQUILLO and M. A. POCA
Stage I: Axonal Membrane Injury and Alterations in Ionic Fluxes. . . . . Stage II: Reversible Cytoske1eta1 Damage .................... . . . . . . . . . . . Stage III: Secondary Axotomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Stage IV: Primary Axotomy..............
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