Amantadine as an Aid to Extubation in Severe Acute Brain Injury: A Case Series.

For a subset of patients with severe acute brain injury (SABI) undergoing invasive mechanical ventilation, the primary barrier to successful extubation is depressed mental status. Amantadine is a neurostimulant that has been demonstrated to increase arousal and improve functional outcomes in patients with SABI. In this case series, we describe 5 patients with SABI and invasive mechanical ventilation who received amantadine as an agent to improve mental status to allow extubation. The primary barrier to extubation for all patients was depressed mental status. Median age was 77 (range 32 to 82). Primary diagnoses were ischemic stroke (n = 1), subdural hemorrhage (n = 2), intracerebral hemorrhage (n = 1), and traumatic brain injury (n = 1). Median Glasgow Coma Score was 7T prior to administration of amantadine and 10T on the day after amantadine was initiated, with improvements in eye-opening and motor response. Four patients displayed improvement in arousal and attention and were successfully extubated 1 to 4 days after initiation of amantadine (median 2 days). The fifth patient only displayed marginal improvement in mental status after starting amantadine, but was ultimately able to be extubated 7 days later. Amantadine may improve the likelihood of or reduce the time to successful extubation in patients with SABI.

Trends and predictors of decompressive craniectomy in acute ischemic stroke, 2011-2020.

INTRODUCTION: Rates of decompressive craniectomy (DC) in acute ischemic stroke (AIS) have been reported to decline over time, attributed to an increase in endovascular therapy (EVT) preventing the development of malignant cerebral edema. We sought to characterize trends in DC in AIS between 2011 and 2020. MATERIAL AND METHODS: We performed a retrospective observational study of U.S. AIS hospitalizations using the National Inpatient Sample, 2011 to 2020. We calculated rates of DC per 10,000 AIS among all AIS hospitalizations, as well as AIS hospitalizations undergoing invasive mechanical ventilation (IMV). A logistic regression to determine predictors of DC was performed. RESULTS: Of ∼4.4 million AIS hospitalizations, 0.5 % underwent DC; of ∼300,000 AIS with IMV, 5.8 % underwent DC. From 2011 to 2020, the rate of DC increased from 37.4 to 59.1 per 10,000 AIS (p < 0.001). The rate of DC in patients undergoing IMV remained stable at ∼550 per 10,000 (p = 0.088). The most important factors predicting DC were age (OR 4.88, 95 % CI 4.53-5.25), hospital stroke volume (OR 2.61, 95 % CI 2.17-3.14), hospital teaching status (OR 1.54, 95 % CI 1.36-1.75), and transfer status (OR 1.53, 95 % CI 1.41-1.66); EVT status did not predict DC. CONCLUSIONS: The rate of DC in AIS has increased between 2011 and 2020. Our findings are contrary to prior reports of decreasing DC rates over time. Increasing EVT rates do not seem to be preventing the occurrence of DC. Future research should focus on the decision-making process for both clinicians and surrogates regarding DC with consideration of long-term outcomes.

Spontaneous Hypothermia As an Indicator of Early Diffuse Anoxic Brain Injury in Post-Cardiac Arrest Patients.

OBJECTIVES: To determine the association between spontaneous hypothermia (SH), defined as initial post-resuscitation core body temperature less than 34°C, and diffuse anoxic brain injury (DABI) on initial CT scan of the head (CTH) in post-cardiac arrest patients. DESIGN SETTING AND PARTICIPANTS: This was a retrospective, observational cohort study. This study was performed at the University of Rochester Medical Center Strong Memorial Hospital. All in-hospital and out-of-hospital cardiac arrest patients with return of spontaneous circulation admitted between January 1, 2022, and October 31, 2022, were included. MAIN OUTCOMES AND MEASURES: The primary outcomes were the odds of DABI on initial CTH for patients with SH compared with patients without SH post-cardiac arrest using a multivariable logistic regression controlling for patient covariates including basic demographics and arrest features. DABI on initial CTH was measured qualitatively and quantitatively using neuroradiologist interpretation and calculated gray-white matter ratio of the basal ganglia, respectively. Secondary outcome measures included length of stay (LOS), inpatient mortality, and those who underwent withdrawal of life-sustaining therapy (WOLST) or progression to brain death. RESULTS: Out of the observed 150 cases of cardiac arrest, 31 patients (21%) had SH. Of the 128 patients who had an initial CTH performed, 27 (21%) had DABI. The adjusted odds ratio of DABI on initial CTH associated with SH was 3.55 (95% CI, 1.08-11.64; p = 0.036) and 2.18 (95% CI, 0.69-6.91; p = 0.182) when DABI was measured qualitatively and quantitatively, respectively, after controlling for multiple covariates. There was a difference observed in LOS between the groups (3 vs. 10 d; p = 0.0005) and this was driven by early WOLST. CONCLUSIONS AND REVELANCE: Patients presenting with SH after cardiac arrest may be at greater risk of early DABI on initial CTH compared with those with higher body temperatures in the post-arrest period. Recognition of early SH may help to risk stratify post-cardiac arrest patients at highest risk of DABI.

Association of Do-Not-Resuscitate orders and in-hospital mortality among patients undergoing cranial neurosurgery.

BACKGROUND: Previous studies identified pre-existing DNR orders as a predictor of mortality after surgery. We sought to evaluate mortality of patients receiving cranial neurosurgery with DNR orders placed at the time of, or within 24 h of admission. METHODS: We performed a retrospective cohort study using the California State Inpatient Database, January 2018 to December 2020. We used International Classification of Diseases, 10th Revision (ICD-10) codes to identify emergent hospitalizations with principal diagnosis of brain injury, including traumatic brain injury [TBI], ischemic stroke [IS], intracerebral hemorrhage [ICH], subarachnoid hemorrhage [SAH], or malignant brain tumor [mBT]. We used procedure and Diagnosis Related Group codes to identify cranial neurosurgery. Patients with DNR were one-to-one matched to non-DNR controls based on diagnosis (exact matching), age, sex, Elixhauser comorbidity index, and organ failure (coarsened matching). The primary outcome was inpatient mortality. RESULTS: In California, 30,384 patients underwent cranial neurosurgery, 2018-2020 (n = 3,112, 10% DNR). DNR patients were older, more often female, more often White, with greater comorbidity and organ system dysfunction. There were 2,505 patients with DNR orders 1:1 matched to controls. Patients with DNR had greater inpatient mortality (56% vs. 23%, p < 0.001; Hazard Ratio 3.11, 95% CI 2.50-3.86), received tracheostomy (Odds Ratio [OR] 0.37, 95% CI 0.24-0.57) and gastrostomy less (OR 0.48, 95% CI 0.39-0.58) compared to controls. Multivariable analysis of the unmatched cohort demonstrated similar results. CONCLUSION: Patients undergoing cranial neurosurgery with early or pre-existing DNR have high inpatient mortality compared to clinically similar non-DNR patients; 1 in 2 died during their hospitalization.

National Cost Estimates of Invasive Mechanical Ventilation and Tracheostomy in Acute Stroke, 2008-2017.

BACKGROUND: Patients with stroke receiving invasive mechanical ventilation (IMV) and tracheostomy incur intense treatment and long hospitalizations. We aimed to evaluate US hospitalization costs for patients with stroke requiring IMV, tracheostomy, or no ventilation. METHODS: We performed a retrospective observational study of US hospitalizations for acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage receiving IMV, tracheostomy, or none using the National Inpatient Sample, 2008 to 2017. We calculated hospitalization costs using cost-to-charge ratios adjusted to 2017 US dollars for inpatients with stroke by ventilation status (no IMV, IMV alone, tracheostomy). RESULTS: Of an estimated 5.2 million (95% CI, 5.1-5.3) acute stroke hospitalizations, 2008 to 2017; 9.4% received IMV alone and 1.4% received tracheostomy. Length of stay for patients without IMV was shorter (median, 4 days; interquartile range [IQR], 2-6) compared with IMV alone (median, 6 days; [IQR, 2-13]), and tracheostomy (median, 25 days; [IQR, 18-36]; P<0.001). Mortality for patients without IMV was 3.2% compared with 51.2% for IMV alone and 9.8% for tracheostomy (P<0.001). Median hospitalization costs for patients without IMV was $9503 (IQR, $6544-$14 963), compared with $23 774 (IQR, $10 900-$47 735) for IMV alone and $95 380 (IQR, $63 921-$144 019) for tracheostomy. Tracheostomy placement in ≤7 days had lower costs compared with placement in >7 days (median, $71 470 [IQR, $47 863-$108 250] versus $102 979 [IQR, $69 563-$152 543]; P<0.001). Each day awaiting tracheostomy was associated with a 2.9% cost increase (95% CI, 2.6%-3.1%). US hospitalization costs for patients with acute stroke were $8.7 billion/y (95% CI, $8.5-$8.9 billion). For IMV alone, costs were $1.8 billion/y (95% CI, $1.7-$1.9 billion) and for tracheostomy $824 million/y (95% CI, $789.7-$858.3 million). CONCLUSIONS: Patients with acute stroke who undergo tracheostomy account for 1.4% of stroke admissions and 9.5% of US stroke hospitalization costs. Future research should focus on the added value to society and patients of IMV and tracheostomy, in particular after 7 days for the latter procedure given the increased costs incurred and poor outcomes in stroke.

Hospital Discharge and Readmissions Before and During the COVID-19 Pandemic for California Acute Stroke Inpatients.

BACKGROUND: Acute stroke therapy and rehabilitation declined during the COVID-19 pandemic. We characterized changes in acute stroke disposition and readmissions during the pandemic. METHODS: We used the California State Inpatient Database in this retrospective observational study of ischemic and hemorrhagic stroke. We compared discharge disposition across a pre-pandemic period (January 2019 to February 2020) to a pandemic period (March to December 2020) using cumulative incidence functions (CIF), and re-admission rates using chi-squared. RESULTS: There were 63,120 and 40,003 stroke hospitalizations in the pre-pandemic and pandemic periods, respectively. Pre-pandemic, the most common disposition was home [46%], followed by skilled nursing facility (SNF) [23%], and acute rehabilitation [13%]. During the pandemic, there were more home discharges [51%, subdistribution hazard ratio 1.17, 95% CI 1.15-1.19], decreased SNF discharges [17%, subdistribution hazard ratio 0.70, 95% CI 0.68-0.72], and acute rehabilitation discharges were unchanged [CIF, p<0.001]. Home discharges increased with increasing age, with an increase of 8.2% for those ≥85 years. SNF discharges decreased in a similar distribution by age. Thirty-day readmission rates were 12.7 per 100 hospitalizations pre-pandemic compared to 11.6 per 100 hospitalizations during the pandemic [p<0.001]. Home discharge readmission rates were unchanged between periods. Readmission rates for discharges to SNF (18.4 vs. 16.7 per 100 hospitalizations, p=0.003) and acute rehabilitation decreased (11.3 vs. 10.1 per 100 hospitalizations, p=0.034). CONCLUSIONS: During the pandemic a greater proportion of patients were discharged home, with no change in readmission rates. Research is needed to evaluate the impact on quality and financing of post-hospital stroke care.

Effect of COVID-19 pandemic on outcomes in intracerebral hemorrhage.

OBJECTIVES: Patients with severe intracerebral hemorrhage (ICH) often suffer from impaired capacity and rely on surrogates for decision-making. Restrictions on visitors within healthcare facilities during the pandemic may have impacted care and disposition for patient with ICH. We investigated outcomes of ICH patients during the COVID-19 pandemic compared to a pre-pandemic period. MATERIALS AND METHODS: We conducted a retrospective review of ICH patients from two sources: (1) University of Rochester Get With the Guidelines database and (2) the California State Inpatient Database (SID). Patients were divided into 2019-2020 pre-pandemic and 2020 pandemic groups. We compared mortality, discharge, and comfort care/hospice. Using single-center data, we compared 30-day readmissions and follow-up functional status. RESULTS: The single-center cohort included 230 patients (n = 122 pre-pandemic, n = 108 pandemic group), and the California SID included 17,534 patients (n = 10,537 pre-pandemic, n = 6,997 pandemic group). Inpatient mortality was no different before or during the pandemic in either cohort. Length of stay was unchanged. During the pandemic, more patients were discharged to hospice in the California SID (8.4% vs. 5.9%, p<0.001). Use of comfort care was similar before and during the pandemic in the single center data. Survivors in both datasets were more likely to be discharged home vs. facility during the pandemic. Thirty-day readmissions and follow-up functional status in the single-center cohort were similar between groups. CONCLUSIONS: Using a large database, we identified more ICH patients discharged to hospice during the COVID-19 pandemic and, among survivors, more patients were discharged home rather than healthcare facility discharge during the pandemic.

Reversal of Advanced Directives in Neurologic Emergencies.

Objective: Patients with advanced directives or Medical Orders for Life-Sustaining Treatment (MOLST), including "Do Not Resuscitate" (DNR) and/or "Do Not Intubate" (DNI), may be candidates for procedural interventions when presenting with acute neurologic emergencies. Such interventions may limit morbidity and mortality, but typically they require MOLST reversal. We investigated outcomes of patients with MOLST reversal for treatment of neurologic emergencies. Methods: We conducted a retrospective chart review from July 1, 2019 to April 30, 2021 of patients with MOLST reversal treated in our NeuroMedicine Intensive Care Unit. Variables collected include neurologic disease, MOLST reversal decision maker, procedural interventions, and outcomes. Results: Twenty-seven patients (18 female, median age 78 years (IQR 73-85 years), median baseline modified Rankin score 1 [IQR 0-2.5] were identified with MOLST reversal. The most common pre-procedural MOLST was DNR/DNI (n=22, 81%), and 93% (n=25) pre-procedural MOLSTs were completed by the patient. MOLSTs were reversed by surrogates in n=23 cases (85%). The median time from MOLST completion to MOLST reversal was 603 days (IQR 45 days to 4 years). The most common neurologic emergency was ischemic stroke (n=14, 52%). Most patients died (n=14, 52%), 26% (n=7) were discharged to skilled nursing, and 22% (n=6) returned to home or assisted living. Conclusions: In neurologic emergencies, urgent shared decision making is needed to ensure goal-concordant care, which may result in reversal of existing advanced directives. Outcomes of patients with MOLST reversal were heterogeneous, emphasizing the importance of deliberate patient-centered care weighing the risks and benefits of each intervention.

Safer Stroke-Dx Instrument: Identifying Stroke Misdiagnosis in the Emergency Department.

BACKGROUND: Missed or delayed diagnosis of acute stroke, or false-negative stroke (FNS), at initial emergency department (ED) presentation occurs in ≈9% of confirmed stroke patients. Failure to rapidly diagnose stroke can preclude time-sensitive treatments, resulting in higher risks of severe sequelae and disability. In this study, we developed and tested a modified version of a structured medical record review tool, the Safer Dx Instrument, to identify FNS in a subgroup of hospitalized patients with stroke to gain insight into sources of ED stroke misdiagnosis. METHODS: We conducted a retrospective cohort study at 2 unaffiliated comprehensive stroke centers. In the development and confirmatory cohorts, we applied the Safer Stroke-Dx Instrument to report the prevalence and documented sources of ED diagnostic error in FNS cases among confirmed stroke patients upon whom an acute stroke was suspected by the inpatient team, as evidenced by stroke code activation or urgent neurological consultation, but not by the ED team. Inter-rater reliability and agreement were assessed using interclass coefficient and kappa values (κ). RESULTS: Among 183 cases in the development cohort, the prevalence of FNS was 20.2% (95% CI, 15.0-26.7). Too narrow a differential diagnosis and limited neurological examination were common potential sources of error. The interclass coefficient for the Safer Stroke-Dx Instrument items ranged from 0.42 to 0.91, and items were highly correlated with each other. The κ for diagnostic error identification was 0.90 (95% CI, 0.821-0.978) using the Safer Stroke-Dx Instrument. In the confirmatory cohort of 99 cases, the prevalence of FNS was 21.2% (95% CI, 14.2-30.3) with similar sources of diagnostic error identified. CONCLUSIONS: Hospitalized patients identified by stroke codes and requests for urgent neurological consultation represent an enriched population for the study of diagnostic error in the ED. The Safer Stroke-Dx Instrument is a reliable tool for identifying FNS and sources of diagnostic error.

A Novel COL4A2 Mutation Associated with Recurrent Strokes.

Mutations in type four collagens, specifically COL4A1 and COL4A2, have been associated with cerebral small vessel disease (SVD), defined as lacunar infarcts, deep intracerebral hemorrhages (ICH), and leukoaraiosis. We present a case of a man with recurrent cerebral infarcts, related to a novel COL4A2 mutation, the p.A1534S variant. Magnetic resonance imaging demonstrated multiple lacunar infarcts, numerous deep and lobar microhemorrhages and advanced leukoaraiosis. Evaluation for COL4A2 mutations should be considered when suspecting a genetic cerebral small vessel disease.

Assessing diagnostic error in cerebral venous thrombosis via detailed chart review.

Background Diagnostic error in cerebral venous thrombosis (CVT) has been understudied despite the harm associated with misdiagnosis of other cerebrovascular diseases as well as the known challenges of evaluating non-specific neurological symptoms in clinical practice. Methods We conducted a retrospective cohort study of CVT patients hospitalized at a single center. Two independent reviewers used a medical record review tool, the Safer Dx Instrument, to identify diagnostic errors. Demographic and clinical factors were abstracted. We compared subjects with and without a diagnostic error using the t-test for continuous variables and the chi-square (χ2) test or Fisher's exact test for categorical variables; an alpha of 0.05 was the cutoff for significance. Results A total of 72 CVT patients initially met study inclusion criteria; 19 were excluded due to incomplete medical records. Of the 53 patients included in the final analysis, the mean age was 48 years and 32 (60.4%) were women. Diagnostic error occurred in 11 cases [20.8%; 95% confidence interval (CI) 11.8-33.6%]. Subjects with diagnostic errors were younger (42 vs. 49 years, p = 0.13), more often women (81.8% vs. 54.8%, p = 0.17), and were significantly more likely to have a past medical history of a headache disorder prior to the index CVT visit (7.1% vs. 36.4%, p = 0.03). Conclusions Nearly one in five patients with complete medical records experienced a diagnostic error. Prior history of headache was the only evaluated clinical factor that was more common among those with an error in diagnosis. Future work on distinguishing primary from secondary headaches to improve diagnostic accuracy in acute neurological disease is warranted.

Bifrontal Biparietal Cruciate Decompressive Craniectomy in Pediatric Traumatic Brain Injury.

BACKGROUND: We investigated a novel surgical approach to decompressive craniectomy (DC), the bifrontal biparietal, or "cruciate," craniectomy, in severe pediatric traumatic brain injury (TBI). Cruciate DC was designed with a fundamentally different approach to intracranial pressure (ICP) control compared to traditional DC. Cruciate DC involves craniectomies in all 4 skull quadrants. The sagittal and coronal bone struts are disarticulated at the skull to allow the decompression of the sagittal sinus and bridging veins in addition to permitting cerebral expansion, thereby maintaining cranial compliance. OBJECTIVE: To characterize ICP control with cruciate DC in pediatric TBI. METHODS: We performed a retrospective review of TBI patients who underwent cruciate DC. We investigated mortality and preoperative and postoperative ICP. Group 1 underwent medical therapy prior to DC and Group 2 required immediate DC. RESULTS: Fifteen of 18 patients survived. In Group 1, mean preoperative ICP was 18.5 mm Hg and mean postoperative ICP was 11.5 mm Hg. In Group 2, mean preoperative ICP was 27.3 mm Hg and mean postoperative ICP was 15.0 mm Hg. CONCLUSION: Cruciate DC was associated with lowering ICP. We observed acute drops in ICP and long-term ICP control. The floating bone struts of the cruciate DC permits the decompression of the sagittal sinus and bridging veins, with maximal relief of cerebral edema.

A Systematic Review of the Efficacy of Levetiracetam in Neonatal Seizures.

OBJECTIVE: Seizures are the most common neurological complication in neonatal intensive care units. Phenobarbital (PB) remains the first-line antiepileptic drug (AED) for neonatal seizures despite known neurotoxicity. Levetiracetam (LEV) is a newer AED not approved for neonates. Retrospective and pilot studies have investigated the use of LEV in neonatal seizures. Our objective was to compare the efficacy of LEV to PB in neonatal seizures based upon published data. METHODS: We searched PubMed to perform a systematic review. We found no studies of LEV with comparison or control groups; therefore, we utilized data from two randomized controlled trials of PB as our comparison group. RESULTS: Five studies of LEV met all inclusion/exclusion criteria. The pooled sample size for LEV was 102 (48 received primary LEV, 54 received secondary LEV). The pooled sample size for primary PB was 52. Complete or near-complete seizure cessation was achieved as follows: primary LEV 37/48 (77%), secondary LEV 34/54 (63%), and primary PB 24/52 (46%). CONCLUSION: Our findings suggest that LEV may be at least as or more effective for neonatal seizures as PB. Our review, though limited, is the first to examine LEV efficacy compared with PB in neonates.

Hemostasis in endoscopic endonasal skull base surgery using the Aquamantys bipolar sealer: Technical note.

BACKGROUND: A major challenge during endoscopic transsphenoidal surgery is adequate intraoperative hemostasis. The Aquamantys® is a relatively new bipolar sealing device which uses radiofrequency energy and saline. This promotes hemostasis while decreasing charring and thermal spread. In this paper, we describe our experience with the Aquamantys® Mini EVS 3.4 Epidural Vein Sealer Bipolar Electrocautery System (Medtronic Advanced Energy, Portsmouth, NH, USA) during endoscopic surgery for tumors of the skull base with particular attention to ergonomic benefits and technical nuances. METHODS: We conducted a retrospective review of all patients undergoing endoscopic surgery for skull base tumors from September 2012 to June 2016 at our institution. All procedures used the Aquamantys® system. 45 cases were identified. RESULTS: Successful hemostasis was achieved in all cases with an average estimated blood loss (EBL) of 46mL (Range 10-250). There were no intraoperative complications. The single-shaft design allowed for excellent manipulation compared to pistol-grip bipolar forceps. The thermal energy provided excellent radial coverage without extensive penetration into viable pituitary tissue. CONCLUSION: To our knowledge, this is the largest series documenting the use of the Aquamantys® system in skull base surgery. The device is easily mobile and highly effective within the endonasal corridor and should be a tool in the repertoire of the endoneurosurgeon. Randomized control trials would be useful in comparing EBL between the Aquamantys® and standard bipolar electrocautery.