Objective: This study compares 2 treatment protocols allowing low vs high continuous IV midazolam (cIV-MDZ) doses. Methods:We compared adults with refractory status epilepticus treated with a protocol allowing for high-dose cIV-MDZ (n 5 100; 2002-2011) with those treated with the previous lower-dose cIV-MDZ (n 5 29; 1996-2000. We collected data on baseline characteristics, cIV-MDZ doses, seizure control, hospital course, and outcome.Results: Median maximum cIV-MDZ dose was 0.4 mg/kg/h (interquartile range [IQR] 0.2, 1.0) for the high-dose group and 0.2 mg/kg/h (IQR 0.1, 0.3) for the low-dose group (p , 0.001) with similar duration of infusion. Median time from status epilepticus onset to cIV-MDZ start was 1 day (IQR 1, 3) for the high-dose group and 2 days (IQR 1, 5) for the low-dose group (p 5 0.016). "Withdrawal seizures" (occurring within 48 hours of discontinuation of cIV-MDZ) were less frequent in the high-dose group (15% vs 64%, odds ratio 0.10, 95% confidence interval 0.03-0.27). "Ultimate cIV-MDZ failure" (patients requiring change to a different cIV antiepileptic medication) and hospital complications were not different between groups. Hypotension was more frequent with higher cIV-MDZ doses but was not associated with worse outcome. Discharge mortality was lower in the high-dose group (40% vs 62%, odds ratio 0.34, 95% confidence interval 0.13-0.92 in multivariate analysis).Conclusions: High-dose cIV-MDZ treatment of refractory status epilepticus can be performed safely, is associated with a lower seizure rate after cIV-MDZ discontinuation, and may be associated with lower mortality than traditional lower-dose protocols. Classification of evidence:This study provides Class III evidence that midazolam at higher infusion rates is associated with a reduction in seizure recurrence within 48 hours after discontinuation and may be associated with lower mortality. Neurology ® 2014;82:359-365 GLOSSARY AED 5 antiepileptic drug; cEEG 5 continuous EEG; CI 5 confidence interval; cIV 5 continuous IV; ICU 5 intensive care unit; IQR 5 interquartile range; MDZ 5 midazolam; OR 5 odds ratio; RSE 5 refractory status epilepticus; SE 5 status epilepticus.Status epilepticus (SE) is a neurologic emergency that requires prompt management.1-3 SE that does not respond to standard treatment regimens is labeled as refractory SE (RSE).2,4 Recent guidelines recommend anesthetic doses of midazolam for these patients, 2 but so far no adequately powered randomized controlled trial has compared different treatment strategies for RSE. 2,5,6 The difficulty of conducting such a study has been recently highlighted by the early termination of a prospective trial comparing propofol and barbiturates for patients with RSE. Thus, the best currently available options for guiding therapy of these very sick patients are careful investigation of the underlying pathophysiology as well as comprehensive observational studies.We previously reported our initial experience with the use of midazolam infusions for the treatment of RSE, 8 after which ...

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Previous proteomic evidence revealed that the content of certain peptide fragments including Vgf-derived peptide aa 398-411 (Vgf398-411) of the precursor Vgf protein in the cerebral spinal fluid (CSF) correctly identified patients with ALS from normal and disease controls. Using quantitative ELISA immunoassay we found that the CSF levels of Vgf decreases with muscle weakness in patients with ALS. In SOD1 G93A transgenic mice, loss of full-length Vgf content in CSF, serum and in SMI-32 immunopositive spinal cord motor neurons is noted in asymptomatic animals (approximately 75 days old) and continues to show a progressive decline as animals weaken. In vitro studies show that viral-mediated exogenous Vgf expression in primary mixed spinal cord neuron cultures attenuates excitotoxic injury. Thus, while Vgf may be a reliable biomarker of progression of muscle weakness in patients with ALS, restoration of Vgf expression in spinal cord motor neurons may therapeutically rescue spinal cord motorneurons against excitotoxic injury.

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OBJECTIVEObservation and neurosurgical intervention for unruptured intracranial aneurysms (UIAs) in the elderly population is rapidly increasing. Cerebral aneurysm coiling (CACo) is favored over cerebral aneurysm clipping (CAC) in elderly patients, yet some elderly individuals still undergo CAC. The cost-effectiveness of treating UIAs requires further exploration. Understanding the effect of intervention on hospital charges and length of stay (LOS) as well as perioperative mortality and complications can further shed light on its economic impact. The purpose of this study was to analyze the cost and perioperative outcomes of UIAs in elderly patients (≥ 65 years of age) after CACo or CAC intervention.METHODSRetrospective cohorts of CACo and CAC admissions were extracted from National (Nationwide) Inpatient Sample data obtained between 2002 and 2013, forming parallel intervention groups to compare the following outcomes between elderly and nonelderly patients: average LOS and mean hospital admission costs, in-hospital mortality, and complications. Covariates included sex, race or ethnicity, and comorbidities.RESULTSElderly patients undergoing CAC experienced an average LOS of 8.0 days, whereas elderly patients undergoing CACo stayed an average of 3.2 days. The mean hospital charges incurred during admission totaled $95,960 in the elderly patients who underwent CAC versus $87,960 in the ones who underwent CACo. Elderly patients in whom CAC was performed had a 2.2% rate of in-hospital mortality, with a 2.6 greater adjusted odds of in-hospital mortality than nonelderly patients treated with CAC. In contrast, elderly patients who underwent CACo had a 1.36 greater adjusted odds of in-hospital mortality than their nonelderly counterparts. Compared to nonelderly patients receiving both interventions, elderly individuals had a significantly higher prevalence of various comorbidities and incidence of complications. Elderly patients who received CAC experienced a 10.3% incidence rate of perioperative stroke, whereas their CACo counterparts experienced this complication at a rate of 3.5%. Elderly patients treated with CAC had greater odds of perioperative acute renal failure, whereas their CACo counterparts had greater odds of perioperative deep venous thrombosis and pulmonary embolism.CONCLUSIONSIntervention with CAC and CACo in the elderly is resource intensive and is associated with higher risk than in the nonelderly. Those deciding between intervention and conservative management should consider these risks and costs, especially the 2.2% postoperative mortality rate associated with CAC in the elderly population. Further comparative cost-effectiveness research is needed to weigh these costs and outcomes against those of conservative management.

OBJECTIVEPatients with medically refractory localization-related epilepsy (LRE) may be candidates for surgical intervention if the seizure onset zone (SOZ) can be well localized. Stereoelectroencephalography (SEEG) offers an attractive alternative to subdural grid and strip electrode implantation for seizure lateralization and localization; yet there are few series reporting the safety and efficacy of SEEG in pediatric patients.METHODSThe authors review their initial 3-year consecutive experience with SEEG in pediatric patients with LRE. SEEG coverage, SOZ localization, complications, and preliminary seizure outcomes following subsequent surgical treatments are assessed.RESULTSTwenty-five pediatric patients underwent 30 SEEG implantations, with a total of 342 electrodes placed. Ten had prior resections or ablations. Seven had no MRI abnormalities, and 8 had multiple lesions on MRI. Based on preimplantation hypotheses, 7 investigations were extratemporal (ET), 1 was only temporal-limbic (TL), and 22 were combined ET/TL investigations. Fourteen patients underwent bilateral investigations. On average, patients were monitored for 8 days postimplant (range 3–19 days). Nearly all patients were discharged home on the day following electrode explantation.There were no major complications. Minor complications included 1 electrode deflection into the subdural space, resulting in a minor asymptomatic extraaxial hemorrhage; and 1 in-house and 1 delayed electrode superficial scalp infection, both treated with local wound care and oral antibiotics.SEEG localized the hypothetical SOZ in 23 of 25 patients (92%). To date, 18 patients have undergone definitive surgical intervention. In 2 patients, SEEG localized the SOZ near eloquent cortex and subdural grids were used to further delineate the seizure focus relative to mapped motor function just prior to resection. At last follow-up (average 21 months), 8 of 15 patients with at least 6 months of follow-up (53%) were Engel class I, and an additional 6 patients (40%) were Engel class II or III. Only 1 patient was Engel class IV.CONCLUSIONSSEEG is a safe and effective technique for invasive SOZ localization in medically refractory LRE in the pediatric population. SEEG permits bilateral and multilobar investigations while avoiding large craniotomies. It is conducive to deep, 3D, and perilesional investigations, particularly in cases of prior resections. Patients who are not found to have focally localizable seizures are spared craniotomies.

BACKGROUND:Frailty, a decline in physiological reserve, prognosticates poorer outcomes for several neurosurgical conditions. However, the impact of frailty on traumatic brain injury outcomes is not well characterized.OBJECTIVE:To analyze the association between frailty and traumatic intracranial hemorrhage (tICH) outcomes in a nationwide cohort.METHODS:We identified all adult admissions for tICH in the National Trauma Data Bank from 2007 to 2017. Frailty was quantified using the validated modified 5-item Frailty Index (mFI-5) metric (range = 0-5), with mFI-5 ≥2 denoting frailty. Analyzed outcomes included in-hospital mortality, favorable discharge disposition, complications, ventilator days, and intensive care unit (ICU) and total length of stay (LOS). Multivariable regression assessed the association between mFI-5 and outcomes, adjusting for patient demographics, hospital characteristics, injury severity, and neurosurgical intervention.RESULTS:A total of 691 821 tICH admissions were analyzed. The average age was 57.6 years. 18.0% of patients were frail (mFI-5 ≥ 2). Between 2007 and 2017, the prevalence of frailty grew from 7.9% to 21.7%. Frailty was associated with increased odds of mortality (odds ratio [OR] = 1.36, P < .001) and decreased odds of favorable discharge disposition (OR = 0.72, P < .001). Frail patients exhibited an elevated rate of complications (OR = 1.06, P < .001), including unplanned return to the ICU (OR = 1.55, P < .001) and operating room (OR = 1.17, P = .003). Finally, frail patients experienced increased ventilator days (+12%, P < .001), ICU LOS (+11%, P < .001), and total LOS (+13%, P < .001). All associations with death and disposition remained significant after stratification for age, trauma severity, and neurosurgical intervention.CONCLUSION:For patients with tICH, frailty predicted higher mortality and morbidity, independent of age or injury severity.