Faculty Bibliography

OBJECTIVE:To determine the incidence and predictors of acute cerebral ischemia and neurologic deterioration in intracerebral hemorrhage (ICH) patients after an institutional protocol change in systolic blood pressure (SBP) target from <160 to <140 mm Hg. METHODS:We retrospectively compared persons admitted with primary ICH before and after a protocol change in SBP target from <160 to <140 mm Hg. The primary outcomes were presence of acute cerebral ischemia on MRI completed within 2 weeks of ICH and acute neurologic deterioration. RESULTS:= 0.022). A minimum SBP ≤120 mm Hg over 72 hours was associated with cerebral ischemia, while no patient with a minimum SBP ≥130 mm Hg had cerebral ischemia. Acute cerebral ischemia was significantly associated with worse discharge NIH Stroke Scale score, while SBP target was not. CONCLUSIONS:Intensive lowering of SBP <140 mm Hg in acute ICH, particularly allowing SBP <120 mm Hg, is associated with increased remote cerebral ischemic lesions and acute neurologic deterioration.

Burn specialists have long recognized the need for and have role modeled a comprehensive approach incorporating relief of distress as part of care during critical illness. More recently, palliative care specialists have become part of the healthcare team in many U.S. hospitals, especially larger academic institutions that are more likely to have designated burn centers. No current literature describes the intersection of palliative care and burn care or integration of primary and specialist palliative care in this unique context. This Perspective gives an overview of burn care; focuses on pain and other symptoms in burn intensive care unit settings; addresses special needs of critically ill burned patients, their families, and clinicians for high-quality palliative care; and highlights potential benefits of integrating primary and specialist palliative care in burn critical care. MEDLINE and the Cumulative Index to Nursing and Allied Health Literature were searched, and an e-mail survey was used to obtain information from U.S. Burn Fellowship Program directors about palliative medicine training. The Improving Palliative Care in the Intensive Care Unit Project Advisory Board synthesized published evidence with their own research and clinical experience in preparing this article. Mortality and severe morbidity for critically ill burned patients remains high. American Burn Association guidelines lay the foundation for a robust system of palliative care delivery, embedding palliative care principles and processes in intensive care by burn providers. Understanding basic burn care, challenges for symptom management and communication, and the culture of the particular burn unit, can optimize quality and integration of primary and specialist palliative care in this distinctive setting.

Introduction: The efficacy of MDCT-based-angiography in management of acute stroke and/or emergent-large-vessel-occlusion is well established. However, concern for contrast-induced nephropathy(CIN) especially in patients with major risk factors like Diabetes & Chronic kidney disease often delays rapid evaluation of ELVO patients. Many published studies report the overall incidence of CIN after administration of IV or IA iodinated contrast and highlight the direct correlation of dose on higher incidence of CIN. None, however, have examined impact of sequential IV-IA bolus for neuroangiographic evaluation on renal function in patients with DM and/or CKD. Methods: A retrospective study of our 2015-2017 stroke database of 168 patients was conducted to identify all patients with preexisting DM and/or CKD who developed CIN during their hospital course. We also reviewed the prevalence of dehydration (BUN/Cr <20), CHF and anemia (Hb <8 g/dL) for these patients on admission. Results: For all 168 patients; average IA, IV and cumulative IV-IA contrast (Omnipaque 350) doses within 24 hours were 89.9, 91.7 and 181.6 cc respectively. 68 patients had DM and/or CKD of which 3 developed CIN. Under the definition of >=25% increase in baseline Cr within 72-120 hours of receiving contrast, all 3 had CIN. However, under the definition of >=0.5 mg/dL increase in Cr within 72 hours, none had CIN. All 3 only had preexisting DM as risk factor and had age appropriate baseline Cr on admission. The baseline Cr for each of the 3 patients were 0.82, 1.17 & 0.47 mg/dL respectively while the elevated Cr were 1.03, 1.17 & 0.76 mg/dL respectively. All 3 returned to within baseline by discharge with no mortality or need for hemodialysis. Conclusions: There is low risk of developing CIN in high risk patients like CKD or DM following rapid sequential dual IV/IA contrast bolus in acute stroke patients and therefore should not delay rapid neuro-angiographic evaluation

Introduction: Adult onset focal dystonia often affects the upper extremities and cervical region but less often the lower extremities. Dystonia is the second most reported movement disorder post-stroke and often has a delayed presentation ranging from weeks to months. Most reports are in cases where there is permanent and substantial tissue injury. The clinical significance of Basal ganglia infarction or petechial hemorrhage following endovascular therapy for MCA occlusion is not well understood. The development of dystonia in the setting of a recanalized LMCA has never been reported before. Methods: A 39-year-old female presented with Left MCA occlusion. She had no other medical history except for an idiopathic left basal ganglia hemorrhagic stroke 6 months ago with residual mild forearm weakness. She underwent urgent mechanical thrombectomy with successful sequential recanalization of her inferior followed by superior division. The latter was complicated by a mild self-limiting subarachnoid hemorrhage in the left sylvian fissure. She had small petechial hemorrhages in the left basal ganglia on MRI. However, she recovered completely in 5 days and was discharged with a NIHSS of 1 (similar to baseline) as well as mRS of 2. Ten months later, she developed a painful, fixed right lower extremity dystonia where her ankle was inverted and plantarflexed with her toes curled. This was treated with multiple anticholinergic & GABAergic medications as well as Botox to only achieve partial success. Currently

OPINION STATEMENT: Anticoagulation is a vital therapy in a number of different disease processes, and is strongly recommended for the prevention of stroke in patients with atrial fibrillation and/or with mechanical prosthetic heart valves. Studies involving patients on oral anticoagulants (OACs) have revealed that ICH can occur eight times more frequently in this population, with an annual estimated incidence of 0.25 to 1.1%. The decision of whether and when to resume anticoagulation following intracranial hemorrhage is challenging and requires an assessment of associated risks and benefits. Clinical data, imaging, and risk factors for both ischemic and hemorrhagic complications may aid in decision-making. Baseline functional status, life expectancy, compliance with therapy, and family support also impact decision analyses. Currently available data suggest that anticoagulation could be safely restarted in select groups of OAC-ICH patients within 4 weeks of intracranial hemorrhage; however, high-quality randomized, clinical trials are needed.

Importance: There are no prospective cohort studies assessing the incidence and spectrum of neurologic manifestations secondary to Zika virus (ZIKV) infection in adults. Objective: To evaluate the rates of acute ZIKV infection among patients hospitalized with Guillain-Barre syndrome (GBS), meningoencephalitis, or transverse myelitis. Design, Setting, and Participants: A prospective, observational cohort study was conducted at a tertiary referral center for neurological diseases in Rio de Janeiro, Brazil, between December 5, 2015, and May 10, 2016, among consecutive hospitalized adults (>18 years of age) with new-onset acute parainfectious or neuroinflammatory disease. All participants were tested for a series of arbovirosis. Three-month functional outcome was assessed. Interventions: Samples of serum and cerebrospinal fluid were tested for ZIKV using real-time reverse-transcriptase-polymerase chain reaction and an IgM antibody-capture enzyme-linked immunosorbent assay. Clinical, radiographic (magnetic resonance imaging), electrophysiological, and 3-month functional outcome data were collected. Main Outcomes and Measures: The detection of neurologic complications secondary to ZIKV infection. Results: Forty patients (15 women and 25 men; median age, 44 years [range, 22-72 years]) were enrolled, including 29 patients (73%) with GBS (90% Brighton level 1 certainty), 7 (18%) with encephalitis, 3 (8%) with transverse myelitis, and 1 (3%) with newly diagnosed chronic inflammatory demyelinating polyneuropathy. Of these, 35 patients (88%) had molecular and/or serologic evidence of recent ZIKV infection in the serum and/or cerebrospinal fluid. Of the patients positive for ZIKV infection, 27 had GBS (18 demyelinating, 8 axonal, and 1 Miller Fisher syndrome), 5 had encephalitis (3 with concomitant acute neuromuscular disease), 2 had transverse myelitis, and 1 had chronic inflammatory demyelinating polyneuropathy. Admission to the intensive care unit was required for 9 patients positive for ZIKV infection (26%), and 5 (14%) required mechanical ventilation. Compared with admission during the period from December 5, 2013, to May 10, 2014 (before the Brazilian outbreak of ZIKV), admissions for GBS increased from a mean of 1.0 per month to 5.6 per month, admissions for encephalitis increased from 0.4 per month to 1.4 per month, and admissions for transverse myelitis remained constant at 0.6 per month. At 3 months, 2 patients positive for ZIKV infection (6%) died (1 with GBS and 1 with encephalitis), 18 (51%) had chronic pain, and the median modified Rankin score among survivors was 2 (range, 0-5). Conclusions and Relevance: In this single-center Brazilian cohort, ZIKV infection was associated with an increase in the incidence of a diverse spectrum of serious neurologic syndromes. The data also suggest that serologic and molecular testing using blood and cerebrospinal fluid samples can serve as a less expensive, alternative diagnostic strategy in developing countries, where plaque reduction neutralization testing is impractical.

Thrombosis is a leading cause of morbidity and mortality in the United States. Arterial and venous thromboses are implicated in the pathogenesis of major disorders, including myocardial infarction, ischemic stroke, and venous thromboembolism. Over the past decade, direct oral anticoagulants (DOACs) (eg, direct thrombin inhibitor and factor Xa [FXa] inhibitors) have been adopted as alternatives to warfarin due to their clinical advantages and efficacy for the treatment of thrombosis. As with all anticoagulants, treatment with DOACs is associated with a risk of major bleeding, including life-threatening gastrointestinal bleeds and intracranial hemorrhages (ICHs). In turn, the burden of bleeding associated with DOAC treatment is itself associated with substantial healthcare costs that are amplified by an increased risk of thromboembolic events and mortality following major bleeding events, especially in patients with ICHs. Given the rapid adoption of the DOACs and projected usage in the large patient population affected by thromboembolic conditions, clinicians are increasingly likely to encounter patients with major bleeding events due to DOAC therapy. Unlike warfarin, effective strategies to manage these bleeds are limited. There is an unmet need for reversal agents for use in the management of patients who receive FXa inhibitors and experience life-threatening bleeding or need emergency surgery. Andexanet alfa and ciraparantag are being evaluated as potential antidotes for both direct and indirect FXa inhibitors.

Introduction: Acute brain injury incurred after aneurysm rupture in subarachnoid hemorrhage (SAH) is a major predictor of poor functional outcome. We hypothesize that platelet-leukocyte aggregates (PLA) form early after SAH and contribute to acute brain injury. Methods: A prospective study of antiplatelet-naive SAH patients and controls (patients with unruptured aneurysms undergoing repair) was conducted from 3/2014-3/2016. Platelet-monocyte, platelet-lymphocyte and platelet-neutrophil aggregates in whole blood were measured with and without exposure to a platelet agonist (Thrombin receptor activating peptide [TRAP]) using flow cytometry. PLA within 24h and averaged over 72h from ictus (prior to the onset of delayed cerebral ischemia/vasospasm) were compared between patients with mild (admission Hunt-Hess [HH] 1-3) versus severe early brain injury (EBI; HH 4-5). Results: We enrolled 60 SAH patients and 13 controls. PLA were significantly lower in those with severe EBI compared to those with mild EBI (Platelet-monocyte-aggregates 36% versus 53%, P=0.011; Plateletneutrophil-aggregates 15.2 versus 23.1%, P=0.002) within 24h of ictus and prior to aneurysm repair and remained significantly lower over 72h (both P<0.05). Platelet-monocyte, platelet-neutrophil and plateletlymphocyte aggregates were also significantly lower in those with severe EBI compared to controls (all P<0.05). The ability of platelets to be stimulated/activated by TRAP to form PLA was also lower in severe EBI patients compared to mild EBI and control patients over 72h (platelet-neutrophil-aggregates 79.7, 88.2 and 92.7%, respectively, P=0.003; platelet-lymphocyte aggregates 9.2, 11.0 and 14.6%, respectively, P=0.022), consistent with prior platelet activation/degranulation. Conclusions: PLA are lower, and respond less to stimulation in patients with severe EBI after SAH compared to those with mild EBI and controls. These data suggest that in severe EBI: PLA may form earlier and are cleared, are adherent to endothelium and not shed in the blood, or have migrated into the parenchyma. These hypotheses bear further study