Cerebral Edema

Assessment and management of cerebral edema and intracranial hypertension in acute liver failure

Authors: Mohsenin V.

Acute liver failure is uncommon but not a rare complication of liver injury. It can happen after ingestion of acetaminophen and exposure to toxins and hepatitis viruses. The defining clinical symptoms are coagulopathy and encephalopathy occurring within days or weeks of the primary insult in patients without preexisting liver injury. Acute liver failure is often complicated by multiorgan failure and sepsis. The most life-threatening complications are sepsis, multiorgan failure, and brain edema. The clinical signs of increased intracranial pressure (ICP) are nonspecific except for neurologic deficits in impending brain stem herniation. Computed tomography of the brain is not sensitive enough in gauging intracranial hypertension or ruling out brain edema. Intracranial pressure monitoring, transcranial Doppler, and jugular venous oximetry provide valuable information for monitoring ICP and guiding therapeutic measures in patients with encephalopathy grade III or IV. Osmotic therapy using hypertonic saline and mannitol, therapeutic hypothermia, and propofol sedation are shown to improve ICPs and stabilize the patient for liver transplantation. In this article, diagnosis and management of hepatic encephalopathy and cerebral edema in patients with acute liver failure are reviewed.

Bradykinin in Blood and CSF after Acute Cerebral Lesions - Correlations with Cerebral Edema and Intracranial Pressure

Authors: Kunz M, Nussberger J, Holtmannspoetter M, Bitterling H, Plesnila N, Zausinger S.

Bradykinin (BK) was shown to stimulate the production of physiologically active metabolites, blood-brain-barrier disruption and brain edema. Purpose of this prospective study was to measure BK concentrations in blood and cerebrospinal fluid (CSF) of patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH) and ischemic stroke and to correlate BK levels with the extent of cerebral edema and intracranial pressure (ICP). Blood and CSF samples of 29 patients suffering from acute cerebral lesions (TBI: 7, SAH: 10, ICH: 8, ischemic stroke: 4) were collected for up to 8 days after the insult. 7 patients with lumbar drainage were used as controls. Edema (5-point scale), ICP, and the GCS (Glasgow Coma Score) at the time of sample withdrawal were correlated with BK concentrations. While all plasma-BK samples were not significantly elevated, CSF-BK levels of all patients were significantly elevated in overall (n=73) and in early (≤72h) measurements (n=55) (4.3±6.9 fmol/ml and 5.6±8.9 fmol/ml) compared to 1.2±0.7 fmol/ml of the controls (p=0.05 and p=0.006). Within 72h after ictus patients suffering from TBI (p=0.01), ICH (p=0.001) and ischemic stroke (p=0.02) showed significant increases. CSF-BK concentrations correlated with the extent of edema formation (r=0.53, p<0.001) and with ICP (r=0.49, p<0.001). Our results demonstrate that acute cerebral lesions are associated with increased CSF-BK levels. Especially after TBI, subarachnoid and intracerebral hemorrhage CSF-BK levels correlate with the extent of edema evolution and ICP. Bradykinin-blocking agents may turn out to be effective remedies in brain injuries.

Delayed Intracranial Hypertension and Cerebral Edema in Severe Pediatric Head Injury: Risk Factor Analysis

Authors: Bennett Colomer C, Solari Vergara F, Tapia Perez F, Miranda Vasquez F, Horlacher Kunstmann A, Parra Fierro G, Salazar Zenkovich C.

Introduction: Diffuse brain edema has been described as a major cause of intracranial hypertension (IH) following traumatic brain injury (TBI), and several studies suggest that it may be more frequent in children than in adults. While most cases of IH following TBI are present from the beginning, several studies have described a subgroup of patients with delayed elevations in intracranial pressure (ICP). Methods: Retrospective review of severe pediatric TBI cases admitted to a single institution during a 6-year period. Patients were classified into three groups, based on the temporal evolution of ICP: patients who evolved without IH, patients who had IH at admission and patients with delayed IH. A risk factor analysis was performed to find differences between these groups. Results: 31 cases of severe pediatric TBI were analyzed. 13 patients were female and 18 male, with an average age of 8.9 years. 4 patients met the described criteria for delayed IH; the only significant risk factor was presence of edema at the initial brain CT (p = 0.008). 3 additional patients presented clinical deterioration after 48 h and signs of brain edema in the CT, after ICP monitoring had been discontinued. Conclusions: Late-onset IH is a relatively common clinical condition in the pediatric population with severe TBI (present in 13% of the cases in our series), and the presence of a Marshall III CT scan at admission is a significant risk factor for this condition. Pediatric patients may benefit from a more prolonged period of ICP monitoring than adults, and the lack of amelioration of brain edema at follow-up brain CT (even with normal ICP values) may be an indication that more prolonged monitoring is needed.

Induced and Sustained Hypernatremia for the Prevention and Treatment of Cerebral Edema Following Brain Injury

Authors: Ryu JH, Walcott BP, Kahle KT, Sheth SA, Peterson RT, Nahed BV, Coumans JV, Simard JM.

Cerebral edema develops in response to and as a result of a variety of neurologic insults such as ischemic stroke, traumatic brain injury, and tumor. It deforms brain tissue, resulting in localized mass effect and increase in intracranial pressure (ICP) that are associated with a high rate of morbidity and mortality. When administered in bolus form, hyperosmolar agents such as mannitol and hypertonic saline have been shown to reduce total brain water content and decrease ICP, and are currently the mainstays of pharmacological treatment. However, surprisingly, little is known about the increasingly common clinical practice of inducing a state of sustained hypernatremia. Herein, we review the available studies employing sustained hyperosmolar therapy to induce hypernatremia for the prevention and/or treatment of cerebral edema. Insufficient evidence exists to recommend pharmacologic induction of hypernatremia as a treatment for cerebral edema. The strategy of vigilant avoidance of hyponatremia is currently a safer, potentially more efficacious paradigm.

Activation of P2X7 Promotes Cerebral Edema and Neurological Injury after Traumatic Brain Injury in Mice

Authors: Kimbler DE, Shields J, Yanasak N, Vender JR, Dhandapani KM.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Cerebral edema, the abnormal accumulation of fluid within the brain parenchyma, contributes to elevated intracranial pressure (ICP) and is a common life-threatening neurological complication following TBI. Unfortunately, neurosurgical approaches to alleviate increased ICP remain controversial and medical therapies are lacking due in part to the absence of viable drug targets. In the present study, genetic inhibition (P2X7-/- mice) of the purinergic P2x7 receptor attenuated the expression of the pro-inflammatory cytokine, interleukin-1β (IL-1β) and reduced cerebral edema following controlled cortical impact, as compared to wild-type mice. Similarly, brilliant blue G (BBG), a clinically non-toxic P2X7 inhibitor, inhibited IL-1β expression, limited edemic development, and improved neurobehavioral outcomes after TBI. The beneficial effects of BBG followed either prophylactic administration via the drinking water for one week prior to injury or via an intravenous bolus administration up to four hours after TBI, suggesting a clinically-implementable therapeutic window. Notably, P2X7 localized within astrocytic end feet and administration of BBG decreased the expression of glial fibrillary acidic protein (GFAP), a reactive astrocyte marker, and attenuated the expression of aquaporin-4 (AQP4), an astrocytic water channel that promotes cellular edema. Together, these data implicate P2X7 as a novel therapeutic target to prevent secondary neurological injury after TBI, a finding that warrants further investigation.

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