Teddy Youn

Brain Death and Management of a Potential Organ Donor in the Intensive Care Unit

The concept of brain death developed with the advent of mechanical ventilation, and guidelines for determining brain death have been refined over time. Organ donation after brain death is a common source of transplant organs in Western countries. Early identification and notification of organ procurement organizations are essential. Management of potential organ donors must take into consideration specific pathophysiologic changes for medical optimization. Future aims in intensive and neurocritical care medicine must include reducing practice variability in the operational guidelines for brain death determination, as well as improving communication with families about the process of determining brain death.

Cerebral Microhemorrhages and Meningeal Siderosis in Infective Endocarditis

Objective: Patients with infective endocarditis (IE) frequently experience cerebral insults, and neurological involvement in IE has been reported to herald a worse prognosis. In this manuscript, we describe a distinctive pattern of findings on susceptibility-weighted imaging (SWI) sequences in subjects with IE. Methods: Patients with IE who underwent SWI MRI at an academic hospital from 2009 to 2014 were retrospectively analyzed. The pattern of findings was compared to SWI findings in groups of subjects with cerebral amyloid angiopathy (CAA) or severe hypertension. Results: Sixty-six subjects with IE were included; 64 (94%) had microhemorrhages and the average number per patient was 21.5. In 11 (17%) patients, microhemorrhages were the only neuroimaging abnormality. The majority of microhemorrhages were between 1 and 3 mm. In a direct comparison of gradient-echo T2* (GRE-T2*) and SWI, many microhemorrhages in this size range were not detected by GRE-T2*. Microhemorrhages in IE involved every part of the brain with a significant predilection for the cerebellum. This pattern was distinct from that seen in hypertension or CAA. Small subarachnoid hemorrhage or meningeal siderosis were also frequently detected in IE, but were not associated with mycotic aneurysms. Interpretation: SWI is a sensitive diagnostic technique for detecting infectious cerebral angiopathy in subjects with IE, producing a pattern of microhemorrhages that were distinct from other common microangiopathies.

Cerebral Edema After Cardiac Arrest: Tell Tale Sign of Catastrophic Injury or a Treatable Complication?

Despite advances in cardiopulmonary resuscitation (CPR) for cardiac arrest being proposed as early as the 1950s [1] and 1960s [2], only in the modern era has the use of specific interventions such as post-arrest therapeutic hypothermia [3] and community-wide emergency medical services, like bystander-initiated CPR and first responder defibrillation [4], consistently demonstrated a benefit to survival. In addition, a recent Cochrane review has determined that the only strategy that has shown improvement in neurologic outcome after cardiac arrest is induction of mild therapeutic hypothermia [5]. Diffuse brain edema early after cardiac arrest is often associated with a dismal neurological examination and poor outcomes, and the use of osmotic agents has not been shown to reverse or improve either. Clear guidance on how to manage cerebral edema post-cardiac arrest has not been established, and efforts in this regard may possibly be futile. Intensivists from prior generations presciently anticipated a need for brain-oriented resuscitative measures and therapies [6]. However, the pathophysiologic mechanisms of cardiac arrest associated with secondary inflammatory and hormonal responses, during and after resuscitation [also known as post-cardiac arrest syndrome (PACS)] [7], and with secondary brain injury like cerebral edema formation have only recently been established from a molecular biologic basis. More recently, water transport channels, such as Aquaporin-4 (AQP4) [8] and Sur1Trmp4 [9], are now being evaluated as potential secondary targets for inhibiting cerebral edema formation after cardiac arrest. The mechanisms of cardiac arrest-induced cerebral edema formation are likely multifactorial; however, one main mechanism thought to be related is the perivascular pool of AQP4, which is rate limiting for water influx during cerebral edema formation and the site of action for osmotic agents that cause brain water efflux [10]. Although it has been known for two decades that the perivascular pool of AQP4 localizes to the astrocyte endfeet adjacent to the blood–brain barrier, progress in the identification of smallmolecule aquaporin inhibitors has been exceedingly slow [11]. In this issue of Neurocritical Care, Nakayama et al. [10] report their results on attenuating cerebral edema and blood–brain barrier disruption after successful resuscitation from an 8-min arrest induced with intravenous potassium chloride in a mouse model. In their series of well-designed experiments, they found that a continuous intravenous infusion of conivaptan, a V1a and V2 antagonist, targeting a serum osmolality goal of approximately 350 mOsm/L, attenuates regional brain edema development, particularly in the caudo-putamen complex and cortex via the perivascular AQP4 pool (areas where the perivascular pool of AQP4 is more prevalent). The novel use of intravenous conivaptan, a dual arginine vasopressin (AVP) receptor antagonist, is thought to be mediated through its antagonism on V1a receptors in the brain via interactions with AQP4, and on V2 receptors by downregulating AQP2 channel expression in the kidney, which can induce diuresis. The efficacy of water efflux requires maintaining a & David M. Greer david.greer@yale.edu

Bilateral Basal Ganglia Necrosis Secondary to Methamphetamine: Basal Ganglia Necrosis and Amphetamines

FIG. 1. Brain MRI findings at admission. T1-weighted sequence reveals decrease signal intensity in basal ganglia bilaterally involving putamen, globus pallidus, internal and external capsule. (B) T2-weigthed sequence, (C) fluid-attenuated inversion recovery sequence, (E) SWI-sequence, and (F) ADC-sequence reveal bilateral basal ganglia hyperintensities involving the internal and external capsule, sparing the thalami with hypointensities within basal ganglia. (D) DWI-sequence reveals small punctuate hyperintensities in the anterior region of left putamen.

Ophthalmic artery occlusion after chiropractic neck manipulation.

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Clinical Reasoning: Acute onset facial droop in a 36-year-old pregnant woman

A 36-year-old woman, G1P0, 22 weeks pregnant, presented to the emergency department for evaluation of acute onset facial droop. Her medical history included ulcerative colitis, primary sclerosing cholangitis, and heterozygosity for the prothrombin G20210A mutation. She was on 10,000 units of subcutaneous heparin twice daily for a previous deep vein thrombosis secondary to her prothrombin mutation; she was noncompliant with prescribed aspirin.

SSEP in Therapeutic Hypothermia Era

Purpose: The reliability of somatosensory evoked potentials (SSEPs) in predicting outcome in comatose survivors of cardiac arrest treated with therapeutic hypothermia (TH) has been questioned. We investigated whether the absence of cortical (N20) responses was a reliable predictor of a nonawakening in the setting of TH. Methods: A retrospective review was conducted in cardiac arrest survivors treated with TH admitted to a single tertiary care hospital from April, 2010 to March, 2013 who underwent SSEP testing at various time points after cardiac arrest. N20 responses were categorized as normal, present but abnormal, bilaterally absent, or inadequate for interpretation. Neurologic outcome was assessed at discharge by the Cerebral Performance Category Scale (CPC). Results: Ninety-three SSEP studies were performed in 73 patients. Fourteen patients had absent N20 responses; all had poor outcome (CPC 4–5). Eleven patients had absent N20 s during hypothermia, three of whom had follow-up SSEPs after rewarming and cortical responses remained absent. Fifty-seven patients had N20 peaks identified and had variable outcomes. Evaluation of 1 or more N20 peaks was limited or inadequate in 11.4% of SSEPs performed during the cooling because of artifact. Conclusions: Somatosensory evoked potentials remain a reliable prognostic indicator in patients undergoing TH. The limited sample size of patients who had SSEP performed during TH and repeated after normothermia added to the effect of self-fulfilling prophecy limit the interpretation of the reliability of this testing when performed during cooling. Further prospective, multicenter, large scale studies correlating cortical responses in SSEPs during and after TH are warranted. Technical challenges are commonplace during TH and caution is advised in the interpretation of suboptimal recordings.

Cerebral Microhemorrhages on Susceptibility Weighted Imaging After Aortic Dissection

Cerebral microhemorrhages (CMHs) are detected on susceptibility weighted (SWI) and gradient recalled echo T2* (GRE-T2*) magnetic resonance imaging (MRI) and are useful biomarkers of microvascular diseases of the brain. Here we describe the characteristics and distribution of cerebral microhemorrhages in a series of subjects with aortic dissection, compared with an age- and sex-matched series of patient with severe, chronic hypertension. CMHs were discovered in 75% of subjects with aortic dissection with a median of 8 per subject and an average diameter of 2.6 mm. CMHs were primarily located within the frontal lobes, parietal lobes and deep white matter tracts in a pattern suggestive of a watershed distribution. The pattern of CMHs after aortic dissection was different from that related to severe hypertension, which may suggest a different mechanism. We propose that injury to distal arterioles from cholesterol micro emboli may account for the pattern of CMH observed after aortic dissection. Aortic dissection is an important mimicker of the neuroimaging findings of cerebral amyloid angiopathy and severe hypertension.