Neurocritical care
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Randomized Controlled Trial Multicenter Study
High Dose Deferoxamine in Intracerebral Hemorrhage (HI-DEF) Trial: Rationale, Design, and Methods.
Hemoglobin degradation products, in particular iron, have been implicated in secondary neuronal injury following intracerebral hemorrhage (ICH). The iron chelator Deferoxamine Mesylate (DFO) exerts diverse neuroprotective effects, reduces perihematoma edema (PHE) and neuronal damage, and improves functional recovery after experimental ICH. We hypothesize that treatment with DFO could minimize neuronal injury and improve outcome in ICH patients. As a prelude to test this hypothesis, we conducted a Phase I, open-label study to determine the tolerability, safety, and maximum tolerated dose (MTD) of DFO in patients with ICH. Intravenous infusions of DFO in doses up to 62 mg/kg/day (up to a maximum of 6000 mg/day) were well-tolerated and did not seem to increase serious adverse events (SAEs) or mortality. We have initiated a multi-center, double-blind, randomized, placebo-controlled, Phase II clinical trial (High Dose Deferoxamine [HI-DEF] in Intracerebral Hemorrhage) to determine if it is futile to move DFO forward to Phase III efficacy evaluation. ⋯ The Hi-Def trial is expected to advance our understanding of the pathopgysiology of secondary neuronal injury in ICH and will provide a crucial "Go/No Go" signal as to whether a Phase III trial to investigate the efficacy of DFO is warranted.
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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. ⋯ 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.
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Review Case Reports
A Major Pitfall to Avoid: Retroclival Hematoma due to Odontoid Fracture.
Retroclival hematoma (RCH) is a rare occurrence. The hemorrhage is usually small and hidden and can be easily missed on CT scan. Here, we report the association of a RCH with an odontoid fracture. ⋯ In the appropriate clinical setting, when a RCH is found, further imaging should be considered to rule out fracture of the cervical spine. Odontoid fractures can lead to compression of the spinal cord or lower medulla. To prevent neurologic injury and subsequent complications, prompt recognition of type II odontoid fracture should lead to immediate spine stabilization.
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In comatose post-cardiac arrest patients, a serum neuron-specific enolase (NSE) level of >33 μg/L within 72 h was identified as a reliable marker for poor outcome in a large Dutch study (PROPAC), and this level was subsequently adopted in an American Academy of Neurology practice parameter. Later studies reported that NSE >33 μg/L is not a reliable predictor of poor prognosis. To test whether different clinical laboratories contribute to this variability, we compared NSE levels from the laboratory used in the PROPAC study (DLM-Nijmegen) with those of our hospital's laboratory (ARUP) using paired blood samples. ⋯ Absolute serum NSE levels of comatose cardiac arrest patients differ between laboratories. Any specific absolute cut-off levels proposed to prognosticate poor outcome should not be used without detailed data on how neurologic outcomes correspond to a particular laboratory's method, and even then only in conjunction with other prognostic variables.
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Although cardiac abnormalities are well described among patients with acute brain injury, they have not been investigated systematically for acute subdural hemorrhage (SDH). We sought to investigate the prevalence and characteristics of cardiac abnormalities in patients with SDH. ⋯ Although we found ECG abnormalities to be common in patients with SDH, they were not associated with SDH characteristics, and classic neurogenic findings were not observed. Myocardial injury was infrequent and not associated with SDH characteristics. While cardiac abnormalities in acute intracerebral injury often are attributed to neurocardiogenic causes, these are unlikely prominent mechanisms in SDH. Other medical causes need to be considered, as this will have important implications for management.