David Roh

Electroencephalographic Periodic Discharges and Frequency-Dependent Brain Tissue Hypoxia in Acute Brain Injury.

Importance Periodic discharges (PDs) that do not meet seizure criteria, also termed the ictal interictal continuum, are pervasive on electroencephalographic (EEG) recordings after acute brain injury. However, their association with brain homeostasis and the need for clinical intervention remain unknown. Objective To determine whether distinct PD patterns can be identified that, similar to electrographic seizures, cause brain tissue hypoxia, a measure of ongoing brain injury. Design, Setting, and Participants This prospective cohort study included 90 comatose patients with high-grade spontaneous subarachnoid hemorrhage who underwent continuous surface (scalp) EEG (sEEG) recording and multimodality monitoring, including invasive measurements of intracortical (depth) EEG (dEEG), partial pressure of oxygen in interstitial brain tissue (PbtO2), and regional cerebral blood flow (CBF). Patient data were collected from June 1, 2006, to September 1, 2014, at a single tertiary care center. The retrospective analysis was performed from September 1, 2014, to May 1, 2016, with a hypothesis that the effect on brain tissue oxygenation was primarily dependent on the discharge frequency. Main Outcomes and Measures Electroencephalographic recordings were visually classified based on PD frequency and spatial distribution of discharges. Correlations between mean multimodality monitoring data and change-point analyses were performed to characterize electrophysiological changes by applying bootstrapping. Results Of the 90 patients included in the study (26 men and 64 women; mean [SD] age, 55 [15] years), 32 (36%) had PDs on sEEG and dEEG recordings and 21 (23%) on dEEG recordings only. Frequencies of PDs ranged from 0.5 to 2.5 Hz. Median PbtO2 was 23 mm Hg without PDs compared with 16 mm Hg at 2.0 Hz and 14 mm Hg at 2.5 Hz (differences were significant for 0 vs 2.5 Hz based on bootstrapping). Change-point analysis confirmed a temporal association of high-frequency PD onset (≥2.0 Hz) and PbtO2 reduction (median normalized PbtO2 decreased by 25% 5-10 minutes after onset). Increased regional CBF of 21.0 mL/100 g/min for 0 Hz, 25.9 mL/100 g/min for 1.0 Hz, 27.5 mL/100 g/min for 1.5 Hz, and 34.7 mL/100 g/min for 2.0 Hz and increased global cerebral perfusion pressure of 91 mm Hg for 0 Hz, 100.5 mm Hg for 0.5 Hz, 95.5 mm Hg for 1.0 Hz, 97.0 mm Hg for 2.0 Hz, 98.0 mm Hg for 2.5 Hz, 95.0 mm Hg for 2.5 Hz, and 67.8 mm Hg for 3.0 Hz were seen for higher PD frequencies. Conclusions and Relevance These data give some support to consider redefining the continuum between seizures and PDs, suggesting that additional damage after acute brain injury may be reflected by frequency changes in electrocerebral recordings. Similar to seizures, cerebral blood flow increases in patients with PDs to compensate for the increased metabolic demand but higher-frequency PDs (>2 per second) may be inadequately compensated without an additional rise in CBF and associated with brain tissue hypoxia, or higher-frequency PDs may reflect inadequacies in brain compensatory mechanisms.

Ultra-early angiographic vasospasm associated with delayed cerebral ischemia and infarction following aneurysmal subarachnoid hemorrhage.

OBJECTIVE The clinical significance of cerebral ultra-early angiographic vasospasm (UEAV), defined as cerebral arterial narrowing within the first 48 hours of aneurysmal subarachnoid hemorrhage (aSAH), remains poorly characterized. The authors sought to determine its frequency, predictors, and impact on functional outcome. METHODS The authors prospectively studied UEAV in a cohort of 1286 consecutively admitted patients with aSAH between August 1996 and June 2013. Admission clinical, radiographic, and acute clinical course information was documented during patient hospitalization. Functional outcome was assessed at 3 months using the modified Rankin Scale. Logistic regression and Cox proportional hazards models were generated to assess predictors of UEAV and its relationship to delayed cerebral ischemia (DCI) and outcome. Multiple imputation methods were used to address data lost to follow-up. RESULTS The cohort incidence rate of UEAV was 4.6%. Multivariable logistic regression analysis revealed that younger age, sentinel bleed, and poor admission clinical grade were significantly associated with UEAV. Patients with UEAV had a 2-fold increased risk of DCI (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.4-3.9, p = 0.002) and cerebral infarction (OR 2.0, 95% CI 1.0-3.9, p = 0.04), after adjusting for known predictors. Excluding patients who experienced sentinel bleeding did not change this effect. Patients with UEAV also had a significantly higher hazard for DCI in a multivariable model. UEAV was not found to be significantly associated with poor functional outcome (OR 0.8, 95% CI 0.4-1.6, p = 0.5). CONCLUSIONS UEAV may be less frequent than has been reported previously. Patients who exhibit UEAV are at higher risk for refractory DCI that results in cerebral infarction. These patients may benefit from earlier monitoring for signs of DCI and more aggressive treatment. Further study is needed to determine the long-term functional significance of UEAV.

Brain Multimodality Monitoring: Updated Perspectives

The challenges posed by acute brain injury (ABI) involve the management of the initial insult in addition to downstream inflammation, edema, and ischemia that can result in secondary brain injury (SBI). SBI is often subclinical, but can be detected through physiologic changes. These changes serve as a surrogate for tissue injury/cell death and are captured by parameters measured by various monitors that measure intracranial pressure (ICP), cerebral blood flow (CBF), brain tissue oxygenation (PbtO2), cerebral metabolism, and electrocortical activity. In the ideal setting, multimodality monitoring (MMM) integrates these neurological monitoring parameters with traditional hemodynamic monitoring and the physical exam, presenting the information needed to clinicians who can intervene before irreversible damage occurs. There are now consensus guidelines on the utilization of MMM, and there continue to be new advances and questions regarding its use. In this review, we examine these recommendations, recent evidence for MMM, and future directions for MMM.

Intracranial Multimodality Monitoring for Delayed Cerebral Ischemia.

Summary: Management of patients with aneurysmal subarachnoid hemorrhage focuses on prevention of rebleeding by early treatment of the aneurysm, as well as detection and management of neurologic and medical complications. Early detection of delayed cerebral ischemia and management of modifiable contributing causes such as vasospasm take a central role, with the goal of preventing irreversible cerebral injury. In efforts to prevent delayed cerebral ischemia, multimodality monitoring has emerged as a promising tool in detecting subclinical physiologic changes before infarction occurs. However, there has been much variability in the utilization of this technology. Recent consensus guidelines discuss the role of multimodality monitoring in acute brain injury. In this review, we evaluate these guidelines and the utility of each modality of multimodality monitoring in aneurysmal subarachnoid hemorrhage.

Outcomes after intracerebral hemorrhage from arteriovenous malformations

Objective: To compare outcomes after intracerebral hemorrhage (ICH) from cerebral arteriovenous malformation (AVM) rupture and other causes of ICH. Methods: We performed a retrospective population-based study using data from the Nationwide Inpatient Sample. We used standard diagnosis codes to identify ICH cases from 2002 to 2011. Our predictor variable was cerebral AVM. Our primary outcomes were inpatient mortality and home discharge. We used logistic regression to compare outcomes between patients with ICH with and without AVM while adjusting for demographics, comorbidities, and hospital characteristics. In a confirmatory analysis using a prospective cohort of patients hospitalized with ICH at our institution, we additionally adjusted for hematoma characteristics and the Glasgow Coma Scale score. Results: Among 619,167 ICH hospitalizations, the 4,485 patients (0.7%, 95% confidence interval [CI] 0.6–0.8) with an AVM were younger and had fewer medical comorbidities than patients without AVM. After adjustment for confounders, patients with AVM had lower odds of death (odds ratio [OR] 0.5, 95% CI 0.4–0.7) and higher odds of home discharge (OR 2.0, 95% CI 1.4–3.0) than patients without AVM. In a confirmatory analysis of 342 patients with ICH at our institution, the 34 patients (9.9%, 95% CI 7.2–13.6) with a ruptured AVM had higher odds of ambulatory independence at discharge (OR 4.4, 95% CI 1.4–13.1) compared to patients without AVM. Conclusions: Patients with ICH due to ruptured AVM have more favorable outcomes than patients with ICH from other causes.

Determinants of Long-term Neurological Recovery Patterns Relative to Hospital Discharge Among Cardiac Arrest Survivors

Objective: To explore factors associated with neurological recovery at 1 year relative to hospital discharge after cardiac arrest. Design: Observational, retrospective review of a prospectively collected cohort. Setting: Medical or surgical ICUs in a single tertiary care center. Patients: Older than 18 years, resuscitated following either in-hospital or out-of-hospital cardiac arrest and considered for targeted temperature management between 2007 and 2013. Interventions: None. Measurements and Main Results: Logistic regressions to determine factors associated with a poor recovery pattern after 1 year, defined as persistent Cerebral Performance Category Score 3–4 or any worsening of Cerebral Performance Category Score relative to discharge status. In total, 30% (117/385) of patients survived to hospital discharge; among those discharged with Cerebral Performance Category Score 1, 2, 3, and 4, good recovery pattern was seen in 54.5%, 48.4%, 39.5%, and 0%, respectively. Significant variables showing trends in associations with a poor recovery pattern (62.5%) in a multivariate model were age more than 70 years (odds ratio, 4; 95% CIs, 1.1–15; p = 0.04), Hispanic ethnicity (odds ratio, 4; CI, 1.2–13; p = 0.02), and discharge disposition (home needing out-patient services (odds ratio, 1), home requiring no additional services (odds ratio, 0.15; CI, 0.03–0.8; p = 0.02), acute rehabilitation (odds ratio, 0.23; CI, 0.06–0.9; p = 0.04). Conclusions: Patients discharged with mild or moderate cerebral dysfunction sustained their risk of neurological worsening within 1 year of cardiac arrest. Old age, Hispanic ethnicity, and discharge disposition of home with out-patient services may be associated with a poor 1 year neurological recovery pattern after hospital discharge from cardiac arrest.

Chronic Subdural Medical Management

Chronic subdural hematomas (cSDHs) that are asymptomatic or have minimal symptoms have become more prevalent, with an increased rate of detection with neuroimaging in the setting of an aging population and increasing use of anticoagulants. These cSDHs have been known to spontaneously resolve, and subsequent efforts have been made to study the role of nonoperative initial medical management strategies in these patients. Current and potential strategies for the medical management of cSDH are discussed.

Unexpected Rapid Improvement and Neurogenic Stunned Myocardium in a Patient With Acute Motor Axonal Neuropathy: A Case Report and Literature Review.

Acute Motor Axonal Neuropathy-type Guillain-Barré Syndrome (GBS) is a subset of GBS with either a rapidly improving or protracted course that was first described in China. We describe a 27-year-old previously healthy woman with weakness that progressed to complete tetraplegia and areflexia within 2 weeks after an upper respiratory illness. A lumbar puncture performed 4 days after onset of neurologic symptoms was inconclusive for GBS, and electromyography revealed complete motor axonal neuropathy. The patient had Mycoplasma pneumoniae in her nares and blood, and several antiganglioside antibodies in her blood. She was treated with plasmapheresis, antibiotics, and physical therapy. Her motor function and reflexes improved rapidly with treatment, and she was able to ambulate within 3 weeks. She also experienced cardiomyopathy, which improved with plasmapheresis. We report a rare case of Mycoplasma pneumonia-associated acute motor axonal neuropathy-type GBS presenting with complete tetraplegia, areflexia, and neurogenic stunned myocardium that rapidly improved with plasmapheresis.

White Blood Cell Count Improves Prediction of Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage

BACKGROUND Immune dysregulation has long been implicated in the development of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE To determine the relationship of inflammatory cell biomarkers with DCI. METHODS We evaluated 849 aSAH patients who were enrolled into a prospective observational cohort study and had a white blood cell (WBC) differential obtained within 72 h of bleed onset. RESULTS WBC count > 12.1 × 109/L (odds ratio 4.6; 95% confidence interval [CI]: 1.9-11, P < 0.001) was the strongest Complete Blood Count (CBC) predictor of DCI after controlling for clinical grade (P < .001), thickness of SAH blood on admission computed tomography (P = .002), and clipping aneurysm repair (P < .001). A significant interaction between clinical grade and WBC count (odds ratio 0.8, 95% CI: 0.6-1.0, P = .02) revealed that good-grade patients with elevated WBC counts (49%: 273/558) had increased odds for DCI indistinguishable from poor-grade patients. Multivariable Cox regression also showed that elevated WBC counts in good-grade patients increased the hazard for DCI to that of poor-grade patients (hazard ratio 2.1, 95% CI 1.3-3.2, P < .001). Receiver operating characteristic curve analysis of good-grade patients revealed that WBC count (area under the curve [AUC]: 0.63) is a stronger DCI predictor than the modified Fisher score (AUC: 0.57) and significantly improves multivariable DCI prediction models (Z = 2.0, P = .02, AUC: 0.73; PPV: 34%; NPV: 92%). CONCLUSION Good-grade patients with early elevations in WBC count have a similar risk and hazard for DCI as poor-grade patients. Good-grade patients without elevated WBC may be candidates to be safely downgraded from the intensive care unit, leading to cost savings for both patient families and hospitals.

Desmopressin administration and rebleeding in subarachnoid hemorrhage: analysis of an observational prospective database

OBJECTIVERebleeding remains a frequent and catastrophic event leading to poor outcome after subarachnoid hemorrhage (SAH). Reduced platelet function after the initial bleed is associated with higher risk of early rebleeding. Desmopressin (DDAVP) is a well-known hemostatic agent, and recent guidelines already suggest its use in individuals exposed to antiplatelet drugs. The authors hypothesized that DDAVP administration in patients with SAH at admission would be associated with lower risks of rebleeding.METHODSThe authors performed an observational cohort study of patients enrolled in the Columbia University SAH Outcome Project between August 1996 and July 2015. The authors compared the rate of rebleeding between patients who were and those who were not treated with DDAVP. After adjustment for known predictors, logistic regression was used to measure the association between treatment with DDAVP and risks of rebleeding.RESULTSAmong 1639 patients with SAH, 12% were treated with DDAVP. The main indication for treatment was suspected exposure to an antiplatelet agent. The overall incidence of rebleeding was 9% (1% among patients treated with DDAVP compared with 8% among those not treated). After adjustment for antiplatelet use and known predictors, treatment with DDAVP was associated with a 45% reduction in the risks of rebleeding (adjusted OR 0.55, 95% CI 0.27-0.97). DDAVP was associated with a higher incidence of hyponatremia but not with thrombotic events or delayed cerebral ischemia.CONCLUSIONSTreatment with DDAVP was associated with a lower risk of rebleeding among patients with SAH. These findings support further study of DDAVP as first-line therapy for medical hemostasis in patients with SAH.