J Head Trauma Rehabil Vol. 20, No. 1, pp. 76–94 c  2005 Lippincott Williams & Wilkins, Inc. Update of Neuropathology and Neurological Recovery After Traumatic Brain Injury John T. Povlishock, PhD; Douglas I. Katz, MD This review focuses on the potential for traumatic brain injury to evoke both focal and diffuse changes within the brain parenchyma, while considering the cellular constituents involved and the subcellular perturbations that contribute to their dysfunction. New insight is provided on the pathobiology of traumatically induced cell body injury and diffuse axonal damage. The conse- quences of axonal damage in terms of subsequent deafferentation and any potential retrograde cell death and atrophy are addressed. The regional and global metabolic sequelae are also consid- ered. This detailed presentation of the neuropathological consequences of traumatic brain injury is used to set the stage for better appreciating the neurological recovery occurring after traumatic injury. Although the pathological and clinical effects of focal and diffuse damage are usually in- termingled, the different clinical manifestations of recovery patterns associated with focal versus diffuse injuries are presented. The recognizable patterns of recovery, involving unconsciousness, posttraumatic confusion/amnesia, and postconfusional restoration, that typically occur across the full spectrum of diffuse injury are described, recognizing that the patient’s long-term recovery may involve more idiosyncratic combinations of dysfunction. The review highlights the relationship of focal lesions to localizing syndromes that may be embedded in the evolving natural history of dif- fuse pathology. It is noted that injuries with primarily focal pathology do not necessarily follow a comparable pattern of recovery with distinct phases. Potential linkages of these recovery pat- terns to the known neuropathological sequelae of injury and various reparative mechanisms are considered and it is proposed that potential biological markers and newer imaging technologies will better define these linkages. Key words: coma, diffuse and focal brain injury, diffuse ax- onal injury, metabolic change, neuronal cell body damage, posttraumatic amnesia, recovery, traumatic brain injury I N THIS RELATIVELY BRIEF REVIEW, we at- tempt to provide a synopsis of recent ad- vances that have occurred in our understand- ing the pathobiology and clinical assessment of traumatic brain injury (TBI). This review is not intended to deal comprehensively with From the Department of Anatomy and Neurobiology, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, Va (Dr Povlishock); and the Department of Neurology, Boston University School of Medicine, Boston, Mass, and the Healthsouth Braintree Rehabilitation Hospital, Braintree, Mass (Dr Katz). Corresponding author: John T. Povlishock, PhD, Depart- ment of Anatomy and Neurobiology, Virginia Com- monwealth University, 1101 East Marshall St, PO Box 980709, Richmond, VA 23298 (e-mail: jtpovlis@ vcu.edu). each feature of TBI. Rather, it is organized as a series of vignettes dealing with important findings in the field with appropriate refer- ence to other review articles addressing each of the considered themes. As little as 25 years ago, it was assumed that the major pathobiol- ogy of TBI was brain edema. Further, it was posited that if the brain edema could be un- derstood and treated then all the morbidity and mortality associated with TBI would be reversed. As will be seen in the following pas- sages, our understanding of TBI is now more complete, albeit this has introduced a new level of complexity. To date, the rationale driv- ing the basic science and clinical investigation and assessment of TBI has varied, yet it has been based primarily on the recognition that TBI is a national healthcare problem, affecting 76