Huimahn Alex Choi

Therapeutic Hypothermia After Recanalization in Patients With Acute Ischemic Stroke

Background and Purpose— Therapeutic hypothermia improves outcomes in experimental stroke models, especially after ischemia-reperfusion injury. We investigated the clinical and radiological effects of therapeutic hypothermia in acute ischemic stroke patients after recanalization. Methods— A prospective cohort study at 2 stroke centers was performed. We enrolled patients with acute ischemic stroke in the anterior circulation with an initial National Institutes of Health Stroke Scale ≥10 who had successful recanalization (≥thrombolysis in cerebral ischemia, 2b). Patients at center A underwent a mild hypothermia (34.5°C) protocol, which included mechanical ventilation, and 48-hour hypothermia and 48-hour rewarming. Patients at center B were treated according to the guidelines without hypothermia. Cerebral edema, hemorrhagic transformation, good outcome (3-month modified Rankin Scale, ⩽2), mortality, and safety profiles were compared. Potential variables at baseline and during the therapy were analyzed to evaluate for independent predictors of good outcome. Results— The hypothermia group (n=39) had less cerebral edema (P=0.001), hemorrhagic transformation (P=0.016), and better outcome (P=0.017) compared with the normothermia group (n=36). Mortality, hemicraniectomy rate, and medical complications were not statistically different. After adjustment for potential confounders, therapeutic hypothermia (odds ratio, 3.0; 95% confidence interval, 1.0–8.9; P=0.047) and distal occlusion (odds ratio, 7.3; 95% confidence interval; 1.3–40.3; P=0.022) were the independent predictors for good outcome. Absence of cerebral edema (odds ratio, 5.4; 95% confidence interval, 1.6–18.2; P=0.006) and no medical complications (odds ratio, 9.3; 95% confidence interval, 2.2–39.9; P=0.003) were also independent predictors for good outcome during the therapy. Conclusions— In patients with ischemic stroke, after successful recanalization, therapeutic hypothermia may reduce risk of cerebral edema and hemorrhagic transformation, and lead to improved clinical outcomes.

Critical Care for Patients with Massive Ischemic Stroke

Malignant cerebral edema following ischemic stroke is life threatening, as it can cause inadequate blood flow and perfusion leading to irreversible tissue hypoxia and metabolic crisis. Increased intracranial pressure and brain shift can cause herniation syndrome and finally brain death. Multiple randomized clinical trials have shown that preemptive decompressive hemicraniectomy effectively reduces mortality and morbidity in patients with malignant middle cerebral artery infarction. Another life-saving decompressive surgery is suboccipital craniectomy for patients with brainstem compression by edematous cerebellar infarction. In addition to decompressive surgery, cerebrospinal fluid drainage by ventriculostomy should be considered for patients with acute hydrocephalus following stroke. Medical treatment begins with sedation, analgesia, and general measures including ventilatory support, head elevation, maintaining a neutral neck position, and avoiding conditions associated with intracranial hypertension. Optimization of cerebral perfusion pressure and reduction of intracranial pressure should always be pursued simultaneously. Osmotherapy with mannitol is the standard treatment for intracranial hypertension, but hypertonic saline is also an effective alternative. Therapeutic hypothermia may also be considered for treatment of brain edema and intracranial hypertension, but its neuroprotective effects have not been demonstrated in stroke. Barbiturate coma therapy has been used to reduce metabolic demand, but has become less popular because of its systemic adverse effects. Furthermore, general medical care is critical because of the complex interactions between the brain and other organ systems. Some challenging aspects of critical care, including ventilator support, sedation and analgesia, and performing neurological examinations in the setting of a minimal stimulation protocol, are addressed in this review.

Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells

Preclinical studies using bone marrow derived cells to treat traumatic brain injury have demonstrated efficacy in terms of blood–brain barrier preservation, neurogenesis, and functional outcomes. Phase 1 clinical trials using bone marrow mononuclear cells infused intravenously in children with severe traumatic brain injury demonstrated safety and potentially a central nervous system structural preservation treatment effect. This study sought to confirm the safety, logistic feasibility, and potential treatment effect size of structural preservation/inflammatory biomarker mitigation in adults to guide Phase 2 clinical trial design. Adults with severe traumatic brain injury (Glasgow Coma Scale 5–8) and without signs of irreversible brain injury were evaluated for entry into the trial. A dose escalation format was performed in 25 patients: 5 controls, followed 5 patients in each dosing cohort (6, 9, 12 ×106 cells/kg body weight), then 5 more controls. Bone marrow harvest, cell processing to isolate the mononuclear fraction, and re‐infusion occurred within 48 hours after injury. Patients were monitored for harvest‐related hemodynamic changes, infusional toxicity, and adverse events. Outcome measures included magnetic resonance imaging‐based measurements of supratentorial and corpus callosal volumes as well as diffusion tensor imaging‐based measurements of fractional anisotropy and mean diffusivity of the corpus callosum and the corticospinal tract at the level of the brainstem at 1 month and 6 months postinjury. Functional and neurocognitive outcomes were measured and correlated with imaging data. Inflammatory cytokine arrays were measured in the plasma pretreatment, posttreatment, and at 1 and 6 month follow‐up. There were no serious adverse events. There was a mild pulmonary toxicity of the highest dose that was not clinically significant. Despite the treatment group having greater injury severity, there was structural preservation of critical regions of interest that correlated with functional outcomes. Key inflammatory cytokines were downregulated. Treatment of severe, adult traumatic brain injury using an intravenously delivered autologous bone marrow mononuclear cell infusion is safe and logistically feasible. There appears to be a treatment signal as evidenced by central nervous system structural preservation, consistent with previous pediatric trial data. Inflammatory biomarkers are downregulated after cell infusion. Stem Cells 2016

Pharmacologic Management of Paroxysmal Sympathetic Hyperactivity After Brain Injury.

ABSTRACT Paroxysmal sympathetic hyperactivity (PSH) is a result of acute brain injury that has been well known for many decades. However, the evidence for management of PSH is almost entirely anecdotal in nature. We reviewed case reports or series of pharmacotherapy management of PSH. These studies mentioned treatment options, but few studies exist to guide treatment strategies. For many years, the syndrome was not clearly understood; therefore, the therapy has focused on control of symptoms. In 2014, a Steering Committee came together to develop a conceptual definition and produced a consensus set of diagnostic criteria. Although understanding the diagnostic criteria is very well needed in management of patients with PSH, pharmacologic management is also crucial. Data describing the drug choices, dosing, and duration of therapy are also sparse. Recognition of appropriate medications is important because PSH is associated with morbidity, longer hospitalization, delaying transfer to rehabilitation units, and increasing cost. In this review article, we discussed the common medications used in the treatment of PSH. Treatment should target symptom abortion, prevention of symptoms, and refractory treatment. Symptom-abortive medications are indicated to control discrete breakthrough episodes, using medications such as morphine and short-acting benzodiazepines. Other medications used for prevention of symptoms and refractory treatment include long-acting benzodiazepines, nonselective &bgr;-blockers, &agr;2 agonists, opioids, and GABA agonists. The mechanisms by which these agents improve symptoms of PSH remain speculative. However, a combination of medications from different classes seems the most effective approach in managing PSH symptoms. There is wide variability in clinical practice with regard to drug choices, dosing, and duration of therapy. Future research needs to be conducted using the new PSH assessment measure to appropriately apply drug management.

Safety and Efficacy of High-Dose Unfractionated Heparin for Prevention of Venous Thromboembolism in Overweight and Obese Patients

To determine the safety and efficacy of high‐dose subcutaneous unfractionated heparin (UFH) for prevention of venous thromboembolism (VTE) in overweight and obese patients.

Nocturnal Desaturation in the Stroke Unit Is Associated With Wake-Up Ischemic Stroke.

Background and Purpose— Wake-up stroke (WUS) represents a quarter of all ischemic strokes and may be a specific subgroup. Nocturnal desaturation secondary to sleep-disordered breathing is an independent risk factor for stroke, but the association between nocturnal desaturation and WUS remains unclear. We investigated the relationship between nocturnal desaturation using oxygen desaturation index and WUS in patients with acute stroke in the stroke unit. Methods— A total of 298 patients admitted for acute ischemic stroke to the stroke unit between July 2013 and May 2015 were enrolled. The oxygen desaturation index was calculated using pulse oximetry data sampled every 1 minute during 9 hours on the first night (10:00 PM–7:00 AM) of the stroke unit admission, and nocturnal desaturation was defined as an oxygen desaturation index of 5 at least per hour. We compared the clinical characteristics and nocturnal desaturations between patients with and without WUS. Results— Among all patients (age, 67.7±12.6 years; male, 54.4%), 26.5% patients had WUS. The proportion of nocturnal desaturation was significantly greater in patients admitted with WUS (29.1% versus 12.3%, P=0.001). The age, sex, risk factors except for hyperlipidemia, stroke severity, and stroke mechanisms were similar between the 2 groups. After adjustment for covariates, it was found that nocturnal desaturation was significantly more common in the WUS group (odds ratio, 3.25; 95% confidence interval, 1.63–6.46). Conclusions— Nocturnal desaturation was more frequently observed in patients admitted with WUS during the first night in the stroke unit. This suggests that nocturnal desaturation is a possible modifiable risk factor for the occurrence of WUS.

Preferential Location for Arterial Dissection Presenting as Golf-Related Stroke

Seven patients with golf-related strokes were imaged and the literature was reviewed for similar cases, which generated a total 14 such occurrences. The most common time of symptom onset occurred during the golf swing and over one-half of patients damaged an extracranial vertebral artery with most dissections involving the right side. Of a total of 14 dissections, 7 patients had complete symptom resolution and returned to normal. SUMMARY: Golf-related stroke has not been systematically reviewed. The purpose of our study was to describe in detail this particular stroke syndrome. Seven patients were analyzed at a university hospital and 7 patients were reviewed from MEDLINE literature. General demographics, symptom onset, neurologic signs, radiologic findings, and outcome were investigated. A total of 14 patients including 7 patients from the MEDLINE search were analyzed; all were men, with a mean age of 46.9 ± 12.8 years. Symptom onset was classified as during the golf swing (n = 9), unknown (n = 3), and after playing golf (n = 2). Most patients (n = 12) showed involvement of the vertebral artery and 2 patients showed involvement of the internal carotid artery (P = .008). Nine dissections were found on the right side, 3 on the left side, and 2 were bilateral (P = .046). Twelve patients had extracranial involvement and 2 patients had intracranial involvement (P = .008). Seven patients returned to normal, 5 returned to independence, 1 had unknown status, and 1 died. The anatomic preference of golf-related craniocervical arterial dissection is associated with the extracranial and vertebrobasilar system with a right-sided tendency as the result of stereotypical rotational movement during a golf swing.

A simple prediction score system for malignant brain edema progression in large hemispheric infarction

Malignant brain edema (MBE) due to hemispheric infarction can result in brain herniation, poor outcomes, and death; outcome may be improved if certain interventions, such as decompressive craniectomy, are performed early. We sought to generate a prediction score to easily identify those patients at high risk for MBE. 121 patients with large hemispheric infarction (LHI) (2011 to 2014) were included. Patients were divided into two groups: those who developed MBE and those who did not. Independent predictors of MBE were identified by logistic regression and a score was developed. Four factors were independently associated with MBE: baseline National Institutes of Health Stroke Scale (NIHSS) score (p = 0.048), Alberta Stroke Program Early Computed Tomography Score (ASPECTS) (p = 0.007), collateral score (CS) (p<0.001) and revascularization failure (p = 0.013). Points were assigned for each factor as follows: NIHSS ≤ 8 (= 0), 9–17 (= 1), ≥ 18 (= 2); ASPECTS≤ 7 (= 1), >8 (= 0); CS<2 (= 1), ≥2 (= 0); revascularization failure (= 1),success (= 0). The MBE Score (MBES) represents the sum of these individual points. Of 26 patients with a MBES of 0 to 1, none developed MBE. All patients with a MBES of 6 developed MBE. Both MBE development and functional outcomes were strongly associated with the MBES (p = 0.007 and 0.002, respectively). The MBE score is a simple reliable tool for the prediction of MBE.

Treatment Strategies to Attenuate Perihematomal Edema in Patients With Intracerebral Hemorrhage

Spontaneous intracerebral hemorrhage (SICH) continues to be a significant cause of neurologic morbidity and mortality throughout the world. Although recent advances in the treatment of SICH have significantly decreased mortality rates, functional recovery has not been dramatically improved by any intervention to date. There are 2 predominant mechanisms of brain injury from intracerebral hemorrhage: mechanical injury from the primary hematoma (including growth of that hematoma), and secondary injury from perihematomal inflammation. For instance, in the hours to weeks after SICH as the hematoma is being degraded, thrombin and iron are released and can result in neurotoxicity, free radical damage, dysregulated coagulation, and harmful inflammatory cascades; this can clinically and radiologically manifest as perihematomal edema (PHE). PHE can contribute to mass effect, cause acute neurologic deterioration in patients, and has even been associated with poor long-term functional outcomes. PHE therefore lends itself to being a potential therapeutic target. In this article, we will review 1) the pathogenesis and time course of the development of PHE, and 2) the clinical series and trials exploring various methods, with a focus on minimally invasive surgical techniques, to reduce PHE and minimize secondary brain injury. Promising areas of continued research also will be discussed.

Antifactor Xa levels vs. activated partial thromboplastin time for monitoring unfractionated heparin. A pilot study

The two most common methods for monitoring unfractionated heparin (UFH) infusion are the activated partial thromboplastin time (aPTT) and the antifactor Xa heparin assay (anti‐Xa). The purpose of this study is to compare the performance of an aPTT protocol vs. an anti‐Xa protocol in adult patients as defined by the time to reach therapeutic range, the percentage of time the values were within the goal range and the number of times laboratory monitoring was conducted. We then analysed the discordance between paired values of anti‐Xa and aPTT.