Seminars in neurology
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Seminars in neurology · Feb 2015
ReviewChronic traumatic encephalopathy: a neurodegenerative consequence of repetitive traumatic brain injury.
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that develops as a result of repetitive mild traumatic brain injury. Chronic traumatic encephalopathy is characterized by a unique pattern of accumulation of hyperphosphorylated tau in neurons and astrocytes. The tau abnormalities begin focally and perivascularly at the depths of the cerebral sulci, spread to the superficial layers of the adjacent cortex, and eventually become widespread throughout the medial temporal lobes, diencephalon, and brainstem. ⋯ To date, CTE can only be diagnosed by postmortem neuropathological examination, although there are many ongoing research studies examining imaging techniques and biomarkers that might prove to have diagnostic utility. Currently, the incidence and prevalence of CTE are unknown, although great strides are being made to better understand the clinical symptoms and signs of CTE. Further research is critically needed to better identify the genetic and environmental risk factors for CTE as well as potential rehabilitation and therapeutic strategies.
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Despite decades of basic and clinical research, treatments to improve outcomes after traumatic brain injury (TBI) are limited. However, based on the recent recognition of the prevalence of mild TBI, and its potential link to neurodegenerative disease, many new and exciting secondary injury mechanisms have been identified and several new therapies are being evaluated targeting both classic and novel paradigms. This includes a robust increase in both preclinical and clinical investigations. ⋯ They address putative new therapies for TBI across both the spectrum of injury severity and the continuum of care, from the field to rehabilitation. They discussTBI therapy using 11 categories, namely, (1) excitotoxicity and neuronal death, (2) brain edema, (3) mitochondria and oxidative stress, (4) axonal injury, (5) inflammation, (6) ischemia and cerebral blood flow dysregulation, (7) cognitive enhancement, (8) augmentation of endogenous neuroprotection, (9) cellular therapies, (10) combination therapy, and (11) TBI resuscitation. The current golden age of TBI research represents a special opportunity for the development of breakthroughs in the field.
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Seminars in neurology · Feb 2015
ReviewNeuropathology of traumatic brain injury: comparison of penetrating, nonpenetrating direct impact and explosive blast etiologies.
The neuropathology of traumatic brain injury (TBI) from various causes in humans is not as yet fully understood. The authors review and compare the known neuropathology in humans with severe, moderate, and mild TBI (mTBI) from nonpenetrating closed head injury (CHI) from blunt impacts and explosive blasts, as well as penetrating head injury (PHI). Penetrating head injury and CHI that are moderate to severe are more likely than mTBI to cause gross disruption of the cerebral vasculature. ⋯ Neuronal injury is more prevalent in PHI and moderate to severe CHI than mTBI. Astrocyte and microglial activation and proliferation are found in all forms of animal TBI models and in severe to moderate TBI in humans. Their activation in mTBI in the human brain has not yet been studied.
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Seminars in neurology · Feb 2015
ReviewPathophysiology and clinical management of moderate and severe traumatic brain injury in the ICU.
Moderate and severe traumatic brain injury (TBI) is the leading cause of morbidity and mortality among young individuals in high-income countries. Its pathophysiology is divided into two major phases: the initial neuronal injury (or primary injury) followed by secondary insults (secondary injury). Multimodality monitoring now offers neurointensivists the ability to monitor multiple physiologic parameters that act as surrogates of brain ischemia and hypoxia, the major driving forces behind secondary brain injury. ⋯ In this review, the authors focus on neuroclinicians and neurointensivists, and discuss the developments in therapeutic strategies aimed at optimizing intracranial pressure and cerebral perfusion pressure, and minimizing cerebral hypoxia. The management of moderate to severe TBI in the intensive care unit is moving away from a pure "threshold-based" treatment approach toward consideration of patient-specific characteristics, including the state of cerebral autoregulation. The authors also include a concise discussion on the management of medical and neurologic complications peculiar to TBI as well as an overview of prognostication.