Symptomatic Cerebral Edema Research Articles

RT-8 POST-IRRADIATION COURSE OF GLIOMAS OF THALAMUS AND BRAINSTEM

Abstract Objective We retrospectively reviewed the post-irradiation course of cases treated with radiotherapy for the gliomas involving thalamus or brainstem. Methods Thirty-seven gliomas involving thalamus or brainstem treated with radiotherapy from 2007 to 2021 in our hospital were included. Median age was 47 (19-79) years, and KPS at the start of irradiation was 80% or less in 26 cases. Tumor localization was thalamus only/brainstem only/both thalamus and brainstem for 20/9/8 cases. Two cases did not undergo biopsy, and the others underwent surgery before irradiation. Two cases underwent partial excision of the lesion near the thalamus, 6 cases underwent partial excision from other than the thalamus-brainstem, and 27 cases underwent biopsy only. The pathological diagnosis based on the WHO classification at the time of surgery was glioblastoma (GBM) in 8 cases, high-grade glioma other than glioblastoma (HGG) in 23 cases (including 9 cases of diffuse midline glioma K27M), and low-grade glioma (LGG) in 6 cases. Results Median observation period was 16(2-66) months. Median PFS/median OS/5-year OS rate were 13 months/25 months/20% in all 37 cases. Median PFS was 66/18/7 months for LGG/ HGG/ GBM, and 5-year OS was 75/16/15%. Symptomatic cerebral edema associated with tumor growth was observed in one GBM 9 months after irradiation. In HGG, 7/23 cases underwent the VP shunting before irradiation, and one case who underwent ventriculostomy before irradiation had a VP shunting created for worsening hydrocephalus 3 months after irradiation. In one case of GBM, a VP shunt was created immediately after surgery. Conclusions Compared to the past reports of gliomas, it was suggested that the localization in thalamic brainstem was a factor for a worse prognosis in HGG.

NCMP-07. CASE SERIES OF REGULARLY SCHEDULED MANNITOL INFUSIONS SHOWING WITH PROLONGED CLINICAL BENEFIT FOR MANAGEMENT OF CEREBRAL EDEMA IN GLIOMAS

Abstract Gliomas account for the vast majority of malignant primary tumors arising in the central nervous system. Elevated intracranial pressure (ICP) may be a potentially devastating complication of brain tumors and hydrocephalus. Brain tumors may occupy significant space causing displacement and compression of delicate structures within a finite intracranial compartment. The compliance relationship is nonlinear and decreases as the combined volume of the intracranial contents increases. When these compensatory mechanisms have been exhausted, significant increases in pressure develop with relatively small increases in volume. The diagnosis of elevated ICP is generally based on clinical findings and corroborated by imaging studies and the patient's medical history. The best therapy for intracranial hypertension (ICH) is the resolution of the proximate cause of elevated ICP such as the evacuation of a blood clot, resection of a tumor, or cerebrospinal fluid (CSF) diversion in the setting of hydrocephalus. If these modalities have been exhausted or unavailable, osmotic diuretics such as mannitol can be utilized. This medication reduces brain volume by drawing free water out of the tissue and into the circulation, where it is excreted by the kidneys, thus dehydrating brain parenchyma. The common belief is that effects are usually present within minutes, peak at approximately one hour, and last 4 to 24 hours. We report a series of 33 patients treated for a minimum of 1 month of regularly scheduled maintenance infusions of Mannitol 1g/kg every two weeks, 64% showed improved clinical outcomes or stabilization of edema clinical symptoms. Patients expressed improvements in headaches, dizziness, and cognitive ability. This supports the bi-weekly maintenance use of Mannitol in glioma patients with symptomatic cerebral edema. A controlled trial should be supported. This series also suggest a mechanism of action with a more durable response than osmotic diuresis.

Microsurgical resection versus stereotactic radiosurgery for low-grade intracranial arteriovenous malformations: A 27-year institutional experience

The role of microsurgery and radiosurgery in the management of low-grade (Spetzler-Martin grade 1 and 2) arteriovenous malformations (AVMs) remains controversial. We aimed to compare outcomes of low-grade AVMs following microsurgery and radiosurgery using a database of AVM patients presenting between 1990 and 2017. Procedure-related complications, obliteration, and functional status at last follow-up were compared between groups. Hemorrhage-free survival was compared using Kaplan-Meier analysis with subgroup analyses by rupture status on presentation. The study involved 233 patients, of which 113 and 120 were treated with microsurgery and radiosurgery, respectively. The complication rates were statistically comparable between both treatment modalities. Mean follow-up time was 5.1 ± 5.2 years. In the complete cohort, there was no significant difference in hemorrhage-free survival between microsurgery and radiosurgery (log-rank p = 0.676, Breslow p = 0.493). When excluding procedure-related hemorrhage and partial resection, hemorrhage-free survival was significantly higher in the surgically treated cohort (log-rank = 0.094, Breslow p = 0.034). The obliteration rate was significantly higher in the surgical cohort (96% vs. 57%, p < 0.001), while functional status was similar. Microsurgery may offer superior hemorrhage-free survival in the early post-treatment period and demonstrates equivalent long-term hemorrhage control and functional outcome at 5 years compared to radiosurgery with nearly complete obliteration rates. Persistent neurologic deficits following microsurgery and symptomatic cerebral edema represent important treatment risks despite low SM grading. Appropriate patient selection even when dealing with low-grade AVMs is advised, as judicious patient selection and emphasis on technical success can minimize procedure-related hemorrhage and the incidence of subtotal resection.

Development of a nomogram for predicting clinical outcome in patients with angiogram-negative subarachnoid hemorrhage.

To the best of our knowledge, this is the largest clinical retrospective study in AN‐SAH patients, and is the first time to establish accurate predictive models paired with bleeding pattern.BackgroundAngiogram‐negative subarachnoid hemorrhage (AN‐SAH) has a definite incidence of delayed cerebral ischemia (DCI) and poor clinical outcomes. The purpose is to screen independent factors and establish a nomogram to guide the clinical therapy and assess post‐discharge prognosis.MethodsWe identified 273 consecutive patients referred to our institute from 2013 to 2018 for AN‐SAH. A nomogram to predict poor outcomes was formulated based on the multivariable models of independent risk factors. The accuracy and discrimination of nomograms were determined in training and internal validation cohorts.ResultsThe overall poor outcome rates of AN‐SAH were 14.3% and 8.7% at 3 months and 12 months, respectively. In addition, perimesencephalic AN‐SAH (PAN‐SAH) presented with a more unfavorable prognosis compared with non‐perimesencephalic AN‐SAH (NPAN‐SAH). The clinical prognosis was associated with the World Federation of Neurosurgical Societies scale (WFNS) (odds ratio, 3.82 [95% CI, 1.15‐12.67] for 3‐month outcome; and odds ratio, 31.69 [95% CI, 3.65‐275.43] for 12‐month outcome), Subarachnoid hemorrhage Early Brain Edema Score (SEBES) (odds ratio, 10.39 [95% CI, 1.98‐54.64] for 3‐month outcome; odds ratio, 10.01 [95% CI, 1.87‐53.73] for 12‐month outcome), and symptomatic vasospasm (odds ratio, 3.16 [95% CI, 1.03‐9.70] for 3‐month outcome; odds ratio, 5.15 [95% CI, 1.34‐19.85] for 12‐month outcome). The nomogram was constructed based on the above features, which represented great predictive value in clinical outcomes.ConclusionsSymptomatic vasospasm, high WFNS, cerebral edema, and NPAN‐SAH after hemorrhage were associated with poor outcome of AN‐SAH. The nomogram with WFNS (3‐5), SEBES (3‐4), vasospasm, and NPAN‐SAH represented a practical approach to provide individualized risk assessment for AN‐SAH patients.

Osmotherapy for malignant cerebral edema in a phase 2 prospective, double blind, randomized, placebo-controlled study of IV glibenclamide

Background/ObjectiveMalignant edema can be a life-threatening complication of large hemispheric infarction (LHI), and is often treated with osmotherapy. In this exploratory analysis of data from the GAMES-RP study, we hypothesized that patients receiving osmotherapy had symptomatic cerebral edema, and that treatment with intravenous (IV) glibenclamide would modify osmotherapy use as compared with placebo. MethodsGAMES-RP was a phase 2 multi-center prospective, double blind, randomized, placebo-controlled study in LHI. Patients were randomized to IV glibenclamide (e.g. IV glyburide) or placebo. Cerebral edema therapies included osmotherapy and/or decompressive craniectomy at the discretion of the treating team. Total bolus osmotherapy dosing was quantified by “osmolar load”. Radiographic edema was defined by dichotomizing midline shift at 24 h. Clinical changes were defined as any increase in NIHSS1a. ResultsOsmotherapy was administered to 40 of the 77 patients at a median of 39 [27–55] h after stroke onset. The median baseline DWI lesion volume was significantly larger in the osmotherapy treated group (167 [146–211] mL v. 139 [112–170] mL; P=0.046). Adjudicated malignant edema (75% v. 16%; P<0.001) was more common in the osmotherapy treated group. There were no differences in the proportion of patients receiving osmotherapy or the median total osmolar load between treatment arms. Most patients (76%) had a decrease in consciousness (NIHSS item 1A ≥1) on the day they began receiving osmotherapy. ConclusionsIn the GAMES-RP trial, osmolar therapies were most often administered in response to clinical symptoms of decreased consciousness. However, the optimal timing of administration and impact on outcome after LHI have yet to be defined.

Postoperative hemodynamic management in patients undergoing resection of cerebral arteriovenous malformations: A retrospective study

Strict control of blood pressure (BP) has been recommended in patients after surgical resection of cerebral arteriovenous malformations (AVM) to prevent postoperative hyperemic complication. The aim of this study was to review the postoperative hemodynamic management in patients after surgical resection of cerebral AVM and the incidence of postoperative intracranial hemorrhage and/or cerebral edema. After the ethics approval, we retrospectively reviewed the medical records of 207 adult patients who underwent elective surgical resection of cerebral AVM from Jan 2005 to Oct 2016 in a single university hospital. We determined the incidence of postoperative symptomatic intracranial hemorrhage and/or cerebral edema, and reviewed the quality of postoperative BP control during the first 72 h postoperatively. Two hundred and seven patients who underwent cerebral AVM resection were included. The median (IQR) of postoperative maximal systolic BP target was 110 (100–120) mmHg but the range was 90–150 mmHg. Failed hemodynamic control was consistently found in half of the patients during the first 72 h postoperatively. The incidence of postoperative intracranial hemorrhage and/or cerebral edema was 4.4% (9/207 patients). All 9 of these patients experienced a hypertensive event prior to their postoperative hyperemic complication. Two patients required induced hypertension to treat postoperative symptomatic cerebral edema. We concluded that postoperative intracranial hemorrhage and/or cerebral edema is not an uncommon complication after surgical resection of cerebral AVM. Further studies are required to develop a more effective strategy to implement strict BP control in the postoperative period.

Cerebral edema induced by laser interstitial thermal therapy and radiotherapy in close succession in patients with brain tumor.

Laser interstitial thermal therapy (LITT) is an image-guided technique that uses high temperature to ablate pathological tissue. Brain tumor patients undergoing LITT may also undergo radiation therapy (RT) either before or after LITT. Both procedures have been reported to increase cerebral edema and thereby the two treatments in close succession may worsen existing edema that can be difficult to control. The purpose of our study was to determine the frequency of increased and/or symptomatic cerebral edema after combined LITT and RT, the radiographic and clinical signs of this cerebral edema, and the treatment required. This is a single center, retrospective study of patients who underwent LITT and RT less than 60 days apart. Brain Magnetic Resonance Imaging (MRI) and clinical information were reviewed at three time points (pre-treatment, post-LITT, and post-RT). The study cohort comprised eight patients: six with glioblastoma, one with anaplastic astrocytoma, and one with metastasis. Pre-treatment MRI showed cerebral edema in seven patients. Post-LITT MRI showed worsening cerebral edema in three patients, of which one was symptomatic. Post-RT MRI showed worsening cerebral edema in one patient. One patient who received RT before LITT had asymptomatic cerebral edema post-RT that improved post-LITT. Three patients required prolonged steroid therapy (>65 days), while two patients required bevacizumab for steroid-refractory edema. LITT and RT treatment in close succession can induce cerebral edema, which can usually be managed successfully with steroids, although the treatment period may be prolonged. A minority of patients may require more aggressive treatment, such as bevacizumab. Lasers Surg. Med. 50:917-923, 2018. © 2018 Wiley Periodicals, Inc.

Treatment of Hyponatremic Encephalopathy in the Critically Ill

Hyponatremic encephalopathy, symptomatic cerebral edema due to a low osmolar state, is a medical emergency and often encountered in the ICU setting. This article provides a critical appraisal and review of the literature on identification of high-risk patients and the treatment of this life-threatening disorder. Online search of the PubMed database and manual review of articles involving risk factors for hyponatremic encephalopathy and treatment of hyponatremic encephalopathy in critical illness. Hyponatremic encephalopathy is a frequently encountered problem in the ICU. Prompt recognition of hyponatremic encephalopathy and early treatment with hypertonic saline are critical for successful outcomes. Manifestations are varied, depending on the extent of CNS's adaptation to the hypoosmolar state. The absolute change in serum sodium alone is a poor predictor of clinical symptoms. However, certain patient specific risks factors are predictive of a poor outcome and are important to identify. Gender (premenopausal and postmenopausal females), age (prepubertal children), and the presence of hypoxia are the three main clinical risk factors and are more predictive of poor outcomes than the rate of development of hyponatremia or the absolute decrease in the serum sodium. In patients with hyponatremic encephalopathy exhibiting neurologic manifestations, a bolus of 100 mL of 3% saline, given over 10 minutes, should be promptly administered. The goal of this initial bolus is to quickly treat cerebral edema. If signs persist, the bolus should be repeated in order to achieve clinical remission. However, the total change in serum sodium should not exceed 5 mEq/L in the initial 1-2 hours and 15-20 mEq/L in the first 48 hours of treatment. It has recently been demonstrated in a prospective fashion that 500 mL of 3% saline at an infusion rate of 100 mL per hour can be given safely. It is critical to recognize the early signs of cerebral edema (nausea, vomiting, and headache) and intervene with IV 3% sodium chloride as this is the time to intervene rather than waiting until more severe symptoms develop. Cerebral demyelination is a rare complication of overly rapid correction of hyponatremia. The principal risk factors for cerebral demyelination are correction of the serum sodium more than 25 mEq/L in the first 48 hours of therapy, correction past the point of 140 mEq/L, chronic liver disease, and hypoxic/anoxic episode.

Cerebral Edema in a Child after Preemptive Kidney Transplantation

Dialysis disequilibrium syndrome (DDS) is characterized by acute neurological manifestations in patients undergoing first dialysis treatment. The mechanisms for the development of DDS include the reverse urea effect, transient intracranial acidosis, and idiogenic osmoles which can increase intracellular osmolality and promote water movement into the brain. We present a case of a 4-year-old child with chronic kidney disease who underwent a preemptive living unrelated donor kidney transplant. He had a 24 mEq/L drop in his sodium concentration, 92% reduction in blood urea nitrogen (BUN) concentration, and a 67 mOsm/kg drop in serum osmolality within 18 hours after transplant, with concurrent development of symptomatic and radiologic cerebral edema, similar to that described in DDS. Mental status rapidly returned to baseline after administration of 3% hypertonic saline. This case highlights the risk of cerebral edema in patients who have a high pretransplant BUN. It emphasizes the need for close monitoring of vital signs, mental status, and electrolytes in children undergoing renal transplant. Hypertonic solutions can be used to prevent or manage cerebral edema in these patients when serum osmolality decreases rapidly. Pretransplant dialysis is another consideration to proactively reduce serum hyperosmolality.

Midline Splenial Lesion after Aneurysmal Subarachnoid Hemorrhage

Background: Midline splenial lesion of the corpus callosum (MSCC) typically shows a diffusion restrictive pattern that is attributable to excitotoxic mechanisms. Recently, it has been reported in a variety of pathologic conditions. However, common pathophysiologic mechanisms of MSCC development are still lacking. We aimed to evaluate clinico-radiologic characteristics of patients with MSCC among those with aneurysmal subarachnoid hemorrhage (aSAH). Methods: We retrospectively reviewed consecutive patients who were diagnosed with aSAH. Patients without overt aneurysm on imaging study, who had poor quality or no MR image were excluded. MSCCs were divided into 2 groups (ovoid and extended) based on the morphological characteristics on diffusion-weighed image (DWI). Results: A total of 12 patients with aSAH had a MSCC on brain MR image. The median patient age was 62 years, and 25% were male. Eight of 12 patients had an ovoid shaped MSCC. Proportion of patients with parenteral nutrition, sodium imbalance and hypoglycemia were 58%, 42% and 8%, respectively. Half of patients with MSCC had a symptomatic vasospasm, cerebral edema and hydrocephalus. Furthermore, all the MSCC patients in the extended shape group had cerebral edema and hydrocephalus. Withdrawal or toxicity of antiepileptic drugs (AEDs) were not identified in any patients. All patients with an MSCC had a poor prognosis at 3 months. Conclusion: In patients with aSAH, MSCC is associated with the development of cerebral edema or hydrocephalus rather than AED withdrawal or toxicity. MSCC is possibly one of the poor prognostic signs in patients with aSAH. J Neurocrit Care 2015;8(2):78-84

Safety and Tolerability of Desmoteplase Within 3 to 9 Hours After Symptoms Onset in Japanese Patients With Ischemic Stroke.

This study investigated the safety and tolerability of desmoteplase administered within 3 to 9 hours after stroke symptoms onset in Japanese patients with acute ischemic stroke. Patients were randomized to treatment with either desmoteplase or placebo in a 2:1 ratio in 2 consecutive cohorts (70 μg/kg and then 90 μg/kg). Included patients had a baseline National Institutes of Health Stroke Scale score of 4 to 24 and occlusion or high-grade stenosis in the middle cerebral artery segment M1 or M2 on magnetic resonance angiography. The incidence of symptomatic intracranial hemorrhage (≤72 hours) was defined as the primary end point. The occurrence of asymptomatic ICH, symptomatic cerebral edemas, and adverse events were other safety outcomes of special interest. Symptomatic intracranial hemorrhage was observed within 72 hours in 2 patients treated with placebo and in 1 patient treated with 70 μg/kg desmoteplase. Any ICH (symptomatic or asymptomatic ICH) within 72 hours were observed in 7 (43.8%) patients treated with placebo, in 8 (50%) patients treated with 70 μg/kg desmoteplase, and in 9 (56.3%) patients treated with 90 μg/kg desmoteplase. Desmoteplase treatment with 70 or 90 μg/kg was not associated with an increased risk of symptomatic cerebral edema compared with placebo. There were no other serious safety concerns associated with desmoteplase. Desmoteplase in both 70 and 90 μg/kg doses had a favorable safety profile and was well tolerated in Japanese patients with acute ischemic stroke when administered 3 to 9 hours after stroke symptoms onset. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01104467.

Insulin dosing in pediatric diabetic ketoacidosis: where to start?

The incidenceof type 1diabetesmellitus is increasing inpediatric populations.1 Although the degree of hyperglycemia and frequencyofketoacidosisat initialpresentationof thosewith type1diabetes have steadily declined,2 diabetic ketoacidosis (DKA) remains the leading cause of death in children and young people (aged <24 years) with type 1 diabetes mellitus.3,4 Cerebral edema can be difficult to recognize and manage in children and represents the major cause of the continuedmortality andmorbidity associatedwith DKA in this population.4 In a report in theNovember2014 issueof JAMAPediatrics, Nallasamy et al5 studied 50 children presenting with DKA after randomizing themto receive standard-dose insulin (0.1U/kg/h)or lowdose insulin (0.05 U/kg/h). The study was powered to detect noninferiority using the rate of decline in blood glucose, until a glucose level of 250 mg/dL or less was reached, as the primary outcome. Secondary outcomes included time to resolution of acidosis, episodesof treatment failure, and incidencesofhypokalemiaand hypoglycemia. The low-dose insulin strategy was found to be noninferior across all outcomemeasures in this open-label clinical trial. The authors used a straightforward study design and had a high recruitment rate, despite the inherent difficulties in performing a study of this nature, particularly in a pediatric population. The results are encouraging, suggesting that a low-dose insulin strategy is a viable treatment option in the treatment of pediatric DKA. Although this study excluded some of the sickest children (symptomatic cerebral edema, septic shock at presentation), JAMAPEDIATRICS

A new strategy of CyberKnife treatment system based radiosurgery followed by early use of adjuvant bevacizumab treatment for brain metastasis with extensive cerebral edema.

Bevacizumab blocks the effects of vascular endothelial growth factor in leakage-prone capillaries and has been suggested as a new treatment for cerebral radiation edema and necrosis. CyberKnife is a new, frameless stereotactic radiosurgery system. This work investigated the safety and efficacy of CyberKnife followed by early bevacizumab treatment for brain metastasis with extensive cerebral edema. The eligibility criteria of the patients selected for radiosurgery followed by early use of adjuvant bevacizumab treatment were: (1) brain tumors from metastasis with one solitary brain lesion and symptomatic extensive cerebral edema; (2) >18 years of age; (3) the patient refused surgery due to the physical conditions and the risk of surgery; (4) no contraindications for bevacizumab. (5) bevacizumab was applied for a minimum of 2 injections and a maximum of 6 injections with a 2-week interval between treatments, beginning within 2 weeks of the CyberKnife therapy; (6) Karnofsky performance status (KPS) ≥30. Tumor size and edema were monitored by magnetic resonance imaging (MRI). Dexamethasone dosage, KPS, adverse event occurrence and associated clinical outcomes were also recorded. Eight patients were accrued for this new treatment. Radiation dose ranged from 20 to 33 Gy in one to five sessions, prescribed to the 61-71 % isodose line. Bevacizumab therapy was administered 3-10 days after completion of CyberKnife treatment for a minimum of two cycles (5 mg/kg, at 2-week intervals). MRI revealed average reductions of 55.8 % (post-gadolinium) and 63.4 % (T2/FLAIR). Seven patients showed significant clinical neurological improvements. Dexamethasone was reduced in all patients, with five successfully discontinuing dexamethasone treatment 4 weeks after bevacizumab initiation. Hypertension, a bevacizumab-related adverse event, occurred in one patient. After 3-8 months, all patients studied were alive and primary brain metastases were under control, 2 developed new brain metastases and underwent salvage CyberKnife treatment. Recurrent edema and emerging radiation necrosis were not observed. CyberKnife radiosurgery followed by early use of bevacizumab is promising and appears safe for treatment of brain metastases with extensive cerebral edema.

Management of the Malignant Middle Cerebral Artery Syndrome

The malignant middle cerebral artery syndrome, characterized by cerebral edema following large anterior circulation ischemic stroke, is a disease entity with high morbidity and mortality that is easy to recognize, but challenging to manage. In this review, we begin by discussing important aspects of the clinical presentation of the syndrome, including risk factors for deterioration. We then discuss medical measures that can be undertaken before symptomatic cerebral edema occurs and then outline both medical and surgical options for subsequent neurologic worsening. Shared decision making with patients' surrogates regarding decompressive craniectomy in the setting of available clinical trial data is addressed. The authors conclude with a brief discussion of promising novel therapies for preventing cerebral edema.

Abstract T P227: The Safety of Pioglitazone for Hematoma Resolution in IntraCerebral Hemorrhage (SHRINC) Trial: Safety Results

Background and Objectives: Peroxisome proliferator activated receptor-gamma agonists, such as pioglitazone (PIO) enhanced hematoma resolution and improved functional recovery in our animal model of intracerebral hemorrhage (ICH). We conducted a translational Phase II randomized, controlled clinical trial to determine the maximum tolerated dose (MTD) of PIO in patients with spontaneous ICH and to explore the rate of hematoma resolution and clinical outcome. Methods: Patients with spontaneous ICH within 24 hours of symptom onset were randomly allocated 1:1 to placebo or PIO. Patients received escalating doses of PIO daily for three days, followed by a 30mg maintenance dose for the duration of treatment. Duration of treatment was when 75% of the ICH had resolved as determined by serial MRI or 10 weeks of treatment, whichever occurred first. The primary safety outcome was mortality at Day 14. Secondary measures of safety include any mortality, symptomatic cerebral edema, congestive heart failure, edema, hypoglycemia, anemia, and hepatotoxicity. Secondary measures of efficacy include hematoma resolution and clinical outcome. The MTD was determined using the Continual Reassessment Method. Results: From March 2009 to April 2013, 84 patients (42 PIO, 42 control) were enrolled into 11 dose tiers, with a planned range from 0.1-2.0 mg/kg/d. Table 1 demonstrates preliminary baseline and clinical characteristics of patients by treatment group. Overall, 2/84 patients died within 2 weeks after ICH; however mortality rate never exceeded prespecified criteria. The study will be complete in October 2013 and the treatment team remains blinded to treatment allocation. Secondary outcomes by treatment group and the MTD of PIO will be reported. Conclusions: We have completed the treatment phase of the SHRINC Trial. Long term follow-up is on-going. These results will provide the foundation for an efficacy trial evaluating PIO as a potential treatment for patients with spontaneous ICH.

The lion's mane sign: surgical results using the bilateral fronto-orbito-nasal approach in large and giant anterior skull base meningiomas

Concerns about extreme peritumoral edema and its ensuing surgical and perioperative complications led the authors to use the bilateral fronto-orbito-nasal approach to remove midline anterior skull base meningiomas that were larger than 4 cm. The authors hypothesize that extreme vasogenic edema exemplified by finger-like hyperintensities extending into the bifrontal white matter and external capsule and/or the extreme capsule, coined the lion's mane sign (LMS), would help identify patients with a challenging postoperative course. They hypothesize that the LMS would better predict symptomatic postoperative cerebral edema than the edema index (EI). This is an observational case series of 9 patients. The authors noted the grade, pathology, tumor volume, EI, and the presence or absence of the LMS in all tumors. They used the intensive unit care (ICU) length of stay as a nonspecific measure reflecting postoperative symptomatic cerebral edema. Comparisons of edema-related postoperative complications and the EI were made between patients with and without an LMS. Bifrontal hyperintensities, extending into at least three-eighths of the length of the external capsules on T2-weighted MRI, seen in 4 of 9 patients, portended a longer postoperative ICU stay. The presence of an LMS better predicted postoperative complications related to cerebral edema than tumor grade, pathology, volume, or EI. The LMS predicts an increased duration of stay in the ICU after a bilateral fronto-orbito-nasal approach for resection of large and giant anterior skull base meningiomas. Furthermore, the LMS better predicted increased length of stay in the ICU than did the EI.

Symptomatic Cerebral Edema Following Radiosurgery for AVMs

Symptomatic Cerebral Edema Following Radiosurgery for AVMs

Increasing Use of Hypertonic Saline Over Mannitol in the Treatment of Symptomatic Cerebral Edema in Pediatric Diabetic Ketoacidosis

Cerebral edema in diabetic ketoacidosis is a devastating complication with significant morbidity and mortality. This entity has traditionally been treated with mannitol, but use of 3% hypertonic saline has become an accepted alternative. We sought to assess if changes in the use of hyperosmolar therapies for treatment of cerebral edema in diabetic ketoacidosis may have influenced mortality over the last decade. Retrospective cohort study. Patients discharged between 1999 and 2009 from 41 children's hospitals that provided data to the Pediatric Health Information System database. A total of 43,107 children (age < 19) with diagnosis codes related to diabetic ketoacidosis were identified and further classified as having cerebral edema if treated with mannitol and/or 3% hypertonic saline. None. Billing for 3% hypertonic saline and mannitol was quantified, and mortality associated with both diabetic ketoacidosis and cerebral edema in diabetic ketoacidosis was examined. Overall mortality in diabetic ketoacidosis was 0.25% and significantly decreased (p < 0.001) over the study period, whereas the frequency of treatment with hyperosmolar agents (3.8%) was unchanged. Use of mannitol as a sole agent decreased from 98% to 49%, 3% hypertonic saline as a sole agent increased from 2% to 39%, and combined therapy increased from 0% to 10%. Use of 3% hypertonic saline alone was associated with a higher mortality than mannitol alone (adjusted odds ratio, 2.71 [95% CI, 1.01-7.26]) in patients treated for cerebral edema. Similar results were obtained after adjustment for the propensity to receive hypertonic saline (adjusted odds ratio, 2.33 [95% CI, 1.07-5.07]) and in the subset of subjects receiving mechanical ventilation (adjusted odds ratio, 3.27 [95% CI, 1.12-9.60]). Hypertonic saline has replaced mannitol as the most commonly used agent at many institutions for treatment of cerebral edema in diabetic ketoacidosis. In our analysis, however, use of hypertonic saline as a sole agent was associated with an increased risk of mortality. Recognizing the limitations of administrative data, we conclude that equipoise regarding choice of therapy for treatment of cerebral edema in diabetic ketoacidosis should be maintained until a more definitive study is performed to guide therapy of this potentially lethal complication.

Antiangiogenic Therapy for Glioblastoma: The Challenge of Translating Response Rate into Efficacy

Glioblastoma are one of the mostly vascularized tumors and are histologically characterized by abundant endothelial cell proliferation. Vascular endothelial growth factor (VEGF) is responsible for a degree of vascular proliferation and vessel permeability leading to symptomatic cerebral edema. Initial excitement generated from the impressive radiographic response rates has waned due to concerns of limited long-term efficacy and the promotion of a treatment-resistant phenotype. Reasons for the discrepancy between high radiographic response rates and lack of survival benefit have led to a focus on identifying potential mechanisms of resistance to antiangiogenic therapy. However, equally important is the need to focus on identification of basic mechanisms of action of this class of drugs, determining the optimal biologic dose for each agent and identify the effect of antiangiogenic therapy on oxygen and drug delivery to tumor to optimize drug combinations. Finally, alternatives to overall survival (OS) need to be pursued using the application of validated parameters to reliably assess neurologic function and quality of life.

Antiangiogenic Therapy for Glioblastoma: The Challenge of Translating Response Rate into Efficacy

Glioblastoma are one of the mostly vascularized tumors and are histologically characterized by abundant endothelial cell proliferation. Vascular endothelial growth factor (VEGF) is responsible for a degree of vascular proliferation and vessel permeability leading to symptomatic cerebral edema. Initial excitement generated from the impressive radiographic response rates has waned due to concerns of limited long-term efficacy and the promotion of a treatment-resistant phenotype. Reasons for the discrepancy between high radiographic response rates and lack of survival benefit have led to a focus on identifying potential mechanisms of resistance to antiangiogenic therapy. However, equally important is the need to focus on identification of basic mechanisms of action of this class of drugs, determining the optimal biologic dose for each agent and identify the effect of antiangiogenic therapy on oxygen and drug delivery to tumor to optimize drug combinations. Finally, alternatives to overall survival (OS) need to be pursued using the application of validated parameters to reliably assess neurologic function and quality of life.