Relationship of Pressure Reactivity Index and Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage.

AIM: Patients with aneurysmal subarachnoid hemorrhage (SAH) continue to have poor functional outcome due to the occurrence of delayed cerebral ischemia (DCI). Although vasospasm represents the primary therapeutic target for mitigating DCI, DCI occurs through multifocal etiologies that involve impaired cerebral autoregulation. Worse pressure reactivity index (PRx) values, which consists of a moving correlation coefficient between intracranial pressures and mean arterial pressures, have been shown to be associated with DCI in non-randomized clinical trials. RESULTS: We discuss two patients that presented with high-grade SAH and comatose exams. Patient one was a 34-year-old male diagnosed with SAH from a ruptured right middle cerebral artery aneurysm. He had intact PRx values (Mean: -0.07 during hospital days 9-19), while having severe, refractory vasospasm. At the conclusion of his hospitalization, he was functionally independent, had negligible DCI, and was successfully discharged home. Patient two was a 78-year-old female diagnosed with SAH from a ruptured anterior communicating artery aneurysm. She had an improving PRx ranging from -0.1 to 0.1 early in her hospitalization. However, upon developing severe vasospasm, her PRx increased to 0.6 (overall PRx from hospital days 4-16 was 0.3), and she suffered from extensive DCI in bilateral middle cerebral and anterior cerebral artery distributions that ultimately resulted in malignant cerebral edema and brain death. CONCLUSION: Cerebral autoregulation as measured by PRx may represent a viable target for neuroprognostication by evaluating DCI risk in patients with SAH who develop severe or refractory vasospasm. Further studies evaluating the role of cerebral autoregulation, PRx, and its pathophysiological role in DCI are warranted.

Abnormal neurological pupil index is associated with malignant cerebral edema after mechanical thrombectomy in large vessel occlusion patients.

BACKGROUND AND OBJECTIVES: Malignant cerebral edema (MCE) is a feared complication in patients suffering from large vessel occlusion. Variables associated with the development of MCE have not been clearly elucidated. Use of pupillometry and the neurological pupil index (NPi) as an objective measure in patients undergoing mechanical thrombectomy (MT) has not been explored. We aim to evaluate variables significantly associated with MCE in patients that undergo MT and hypothesize that abnormal NPi is associated with MCE in this population. METHODS: A retrospective analysis of patients with acute ischemic stroke who had undergone MT at our institution between 2017 and 2020 was performed. Baseline and outcome variables were collected, including NPi values from pupillometry readings of patients within 72 h after the MT. Patients were divided into two groups: MCE versus non-MCE group. A univariate and multivariate analysis was performed. RESULTS: Of 284 acute ischemic stroke patients, 64 (22.5%) developed MCE. Mean admission glucose (137 vs. 173; p < 0.0001), NIHSS on admission (17 vs. 24; p < 0.01), infarct core volume (27.9 vs. 17.9 mL; p = 0.0036), TICI score (p = 0.001), and number of passes (2.9 vs. 1.8; p < 0.0001) were significantly different between the groups. Pupillometry data was present for 64 patients (22.5%). Upon multivariate analysis, abnormal ipsilateral NPi (OR 21.80 95% CI 3.32-286.4; p = 0.007) and hemorrhagic conversion were independently associated with MCE. CONCLUSION: Abnormal NPi and hemorrhagic conversion are significantly associated with MCE in patients following MT. Further investigation is warranted to better define an association between NPi and patient outcomes in this patient population.

Management of Intracranial Hemorrhage in Patients with a Left Ventricular Assist Device: A Systematic Review and Meta-Analysis.

BACKGROUND: Intracranial hemorrhage (ICH) has been reported to occur in up to 23% of patients with left ventricular assist devices (LVADs). Currently, limited data exists to guide neurosurgical management strategies to optimize outcomes in patients with an LVAD who develop ICH. METHODS: A systematic review and meta-analysis of the literature was performed to evaluate the mortality rate in these patients following medical and/or surgical management and to evaluate antithrombotic reversal and resumption strategies after hemorrhage. RESULTS: 17 studies reporting on 3869 LVAD patients and 545 intracranial hemorrhages spanning investigative periods from 1996 to 2019 were included. The rate of ICH in LVAD patients was 10.6% (411/3869) with 58.6% (231/394) being intraparenchymal hemorrhage (IPH), 23.6% (93/394) subarachnoid hemorrhage (SAH), and 15.5% (61/394) subdural hemorrhage (SDH). Total mortality rates for surgical management 65.6% (40/61) differed from medical management at 45.2% (109/241). There was an increased relative risk of mortality (RR=1.45, 95% CI: 1.10-1.91, p = 0.01) for ICH patients undergoing surgical intervention. The hemorrhage subtype most frequently managed with anticoagulation reversal was IPH 81.8% (63/77), followed by SDH 52.2% (12/23), and SAH 39.1% (18/46). Mean number of days until antithrombotic resumption ranged from 6 to 10.5 days. CONCLUSION: Outcomes remain poor, specifically for those undergoing surgery. As experience with this population increases, prospective studies are warranted to contribute to management and prognostication .

Intravenous thrombolysis pretreatment and other predictors of infarct in a new previously unaffected territory (INT) in ELVO strokes treated with mechanical thrombectomy.

INTRODUCTION: One uncommon complication of mechanical thrombectomy (MT) is an infarct in a new previously unaffected territory (infarct in new territory (INT)). OBJECTIVE: To evaluate the predictors of INT with special focus on intravenous thrombolysis(IVT)pretreatmentbefore MT. METHODS: Consecutive patients with emergent large vessel occlusion (ELVO) treated with MT during a 5-year period were evaluated. INT was defined using standardized methodology proposed by ESCAPE investigators. The predictors of INT and its impact on outcomes were investigated. RESULTS: A total of 419 consecutive patients with ELVO received MT (mean age 64±15 years, 50% men, median baseline National Institutes of Health Stroke Scale score 16 points (IQR 11-20), 69% pretreated with IVT). The incidence of INT was lower in patients treated with combination therapy (IVTandMT) than in patients treated with MT alone, respectively (10% vs 20%; p=0.011). The INT group had more patients with posterior circulation occlusions than the group without INT (28% vs 10%, respectively; p<0.001). The rates of 3-month functional independence were lower in patients with INT (30% vs 50%; p=0.007). IVT pretreatment was not independently related to INT (OR=0.75; 95% CI 0.32 to 1.76), and INT did not emerge as an independent predictor of 3-month functional independence (OR=0.69; 95% CI 0.29 to 1.62) on multivariable logistic regression models. Location of posterior circulation occlusion was independently associated with a higher odds of INT (OR=3.33; 95% CI 1.43 to 7.69; p=0.005). CONCLUSIONS: IVT pretreatment is not independently associated with a lower likelihood of INT in patients with ELVO treated with MT. Patients with ELVO with posterior circulation occlusion are more likely to have INT after MT.

Palliative Care Consultation and Effect on Length of Stay in a Tertiary-Level Neurological Intensive Care Unit.

Background: Patients admitted to an acute care setting with a devastating brain injury are at high risk for morbidity and mortality. These patients and their families can benefit from the psychosocial and decision-making support of a palliative care consultation. Objective: We aim to investigate the characteristics and impact of palliative care consultation for patients under the management of neurosurgical and critical care services with a devastating brain injury in a neurological intensive care unit (ICU) at a large tertiary-care hospital. Design: Data were collected by retrospective review of the electronic medical record and metrics collected by the palliative care service. Data were analyzed using descriptive statistics. Linear regression analysis was performed to assess effect of timing of palliative care consultation. Results: Fifty-five patients admitted to the neurological ICU under the management of the neurosurgical service received a palliative care consultation for the following: hemorrhagic stroke (49%), metastatic cancer (22%), and traumatic brain injury (18%). Of these, 73% had at least one neurosurgical intervention. Palliative care was most frequently consulted for assistance in defining a patient's goals of care (88%). When compared with late consultation, early palliative care consultation was significantly associated with shorter mean length of stay (LOS) and positively correlated in linear regression analysis without an effect on mortality. Conclusions: When compared with a late consultation, early palliative care consultation corresponded to shorter LOS without increasing mortality. One reason for this effect may be that palliative care can help to clarify and document goals of care earlier and more concretely.

Minimally invasive endoscopic hematoma evacuation vs best medical management for spontaneous basal-ganglia intracerebral hemorrhage.

BACKGROUND: We conducted a case-control study to assess the relative safety and efficacy of minimally invasive endoscopic surgery (MIS) for clot evacuation in patients with basal-ganglia intracerebral hemorrhage (ICH). METHODS: We evaluated consecutive patients with acute basal-ganglia ICH at a single center over a 42-month period. Patients received either best medical management according to established guidelines (controls) or MIS (cases). The following outcomes were compared before and after propensity-score matching (PSM): in-hospital mortality; discharge National Institutes of Health Stroke Scale score; discharge disposition; and modified Rankin Scale scores at discharge and at 3 months. RESULTS: Among 224 ICH patients, 19 (8.5%) underwent MIS (mean age, 50.9±10.9; 26.3% female, median ICH volume, 40 (IQR, 25-51)). The interventional cohort was younger with higher ICH volume and stroke severity compared with the medically managed cohort. After PSM, 18 MIS patients were matched to 54 medically managed individuals. The two cohorts did not differ in any of the baseline characteristics. The median ICH volume at 24 hours was lower in the intervention group (40 cm3 (IQR, 25-50) vs 15 cm3 (IQR, 5-20); P<0.001). The two cohorts did not differ in any of the pre-specified outcomes measures except for in-hospital mortality, which was lower in the interventional cohort (28% vs 56%; P=0.041). CONCLUSIONS: Minimally invasive endoscopic hematoma evacuation was associated with lower rates of in-hospital mortality in patients with spontaneous basal-ganglia ICH. These findings support a randomized controlled trial of MIS versus medical management for ICH.

Hemicraniectomy for Malignant Middle Cerebral Artery Syndrome: A Review of Functional Outcomes in Two High-Volume Stroke Centers.

BACKGROUND AND PURPOSE: Despite recent landmark randomized controlled trials showing significant benefits for hemicraniectomy (HCT) compared with medical therapy (MT) in patients with malignant middle cerebral artery infarction (MMCAI), HCT rates have not substantially increased in the United States. We sought to evaluate early outcomes in patients with MMCAI who were treated with HCT (cases) in comparison to patients treated with MT due to the perception of procedural futility by families (controls). METHODS: We retrospectively evaluated consecutive patients with acute MMCAI treated in 2 tertiary care centers during a 7-year period. Pretreatment National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at 3 months were documented. Functional independence (FI) and survival without severe disability (SWSD) were defined as mRS of 0-2 and 0-4, respectively. RESULTS: A total of 66 patients (37 cases and 29 controls) fulfilled the study inclusion criteria (mean age 59 ± 15 years, 52% men, median admission NIHSS score: 19 points [interquartile range {IQR}: 16-22]). Cases were younger (51 ± 11 versus 68 ± 13 years; P < .001) and tended to have lower median admission NIHSS than controls (18 [IQR:16-20] versus 20 [IQR:18-23]; P = .072). The rates of FI and SWSD at 3 months were higher in cases than controls (16% versus 0% [P = .031] and 62% versus 0% [P < .001]), while 3-month mortality was lower (24% versus 77%; P < .001). Multivariable Cox regression analyses adjusting for potential confounders identified HCT as the most important predictor of lower risk of 3-month mortality (hazard ratio: .02, 95% confidence interval: .01-0.10; P < .001). CONCLUSIONS: HCT is a critical and effective therapy for patients with MMCAI but cannot provide a guarantee of functional recovery.

Blood pressure levels post mechanical thrombectomy and outcomes in non-recanalized large vessel occlusion patients.

OBJECTIVE: Permissive hypertension may benefit patients with non-recanalized large vessel occlusion (nrLVO) post mechanical thrombectomy (MT) by maintaining brain perfusion. Data evaluating the impact of post-MT blood pressure (BP) levels on outcomes in nrLVO patients are scarce. We investigated the association of the post-MT BP course with safety and efficacy outcomes in nrLVO. METHODS: Hourly systolic BP (SBP) and diastolic BP (DBP) values were prospectively recorded for 24 hours following MT in consecutive nrLVO patients. Maximum, minimum, and mean BP levels were documented. Three-month functional independence (FI) was defined as modified Rankin Scale (mRS) scores of 0-2. RESULTS: A total of 88 nrLVO patients were evaluated post MT. Patients with FI had lower maximum SBP (160±19 mmHg vs 179±23 mmHg; P=0.001) and higher minimum SBP levels (119±12 mmHg vs 108±25 mmHg; P=0.008). Maximum SBP (183±20 mmHg vs 169±23 mmHg; P=0.008) and DBP levels (105±20 mmHg vs 89±18 mmHg; P=0.001) were higher in patients who died at 3 months while minimum SBP values were lower (102±28 mmHg vs 115±16 mmHg; P=0.007). On multivariable analyses, both maximum SBP (OR per 10 mmHg increase: 0.55, 95% CI 0.39 to 0.79; P=0.001) and minimum SBP (OR per 10 mmHg increase: 1.64, 95% CI 1.04 to 2.60; P=0.033) levels were independently associated with the odds of FI. Maximum DBP (OR per 10 mmHg increase: 1.61; 95% CI 1.10 to 2.36; P=0.014) and minimum SBP (OR per 10 mmHg increase: 0.65, 95% CI 0.47 to 0.90; P=0.009) values were independent predictors of 3-month mortality. CONCLUSIONS: Our study demonstrates that wide BP excursions from the mean during the first 24 hours post MT are associated with worse outcomes in patients with nrLVO.

Admission hyperglycemia and outcomes in large vessel occlusion strokes treated with mechanical thrombectomy.

BACKGROUND AND PURPOSE: Higher admission serum glucose levels have been associated with poor outcomes in patients with acute ischemic stroke (AIS) treated with IV thrombolysis. We sought to evaluate the association of admission serum glucose with early outcomes of patients with emergent large vessel occlusion (ELVO) treated with mechanical thrombectomy (MT). METHODS: Consecutive AIS patients due to ELVO treated with MT in three tertiary stroke centers were evaluated. The following outcomes were documented using standard definitions: symptomatic intracranial hemorrhage (sICH), complete reperfusion, mortality, functional independence (modified Rankin Scale (mRS) score of 0-2), and functional improvement (shift in mRS score) at 3 months. The association of admission serum glucose and admission hyperglycemia (>140 mg/dL) with outcomes was evaluated using univariable and multivariable binary and ordinal logistic regression models. RESULTS: 231 AIS patients with ELVO (mean age 62±14 years, 51% men, median admission National Institute of Health Stroke Scale score 16 points (IQR 12-21), median admission serum glucose 125 mg/dL (IQR 104-162)) were treated with MT. Admission hyperglycemia was associated with a lower likelihood of functional improvement (common OR 0.53; 95% CI 0.31 to 0.97; p=0.027) and higher odds of 3 month mortality (OR 2.76; 95% CI 1.40 to 5.44; p=0.004) in multivariable analyses adjusting for potential confounders. A 10 mg/dL increase in admission blood glucose was associated with a higher likelihood of sICH (OR 1.07; 95% CI 1.01 to 1.13; p=0.033) and 3 month mortality (OR 1.07; 95% CI 1.02 to 1.12; p=0.004) in multivariable models. There was no association between admission serum glucose or hyperglycemia and complete reperfusion. CONCLUSIONS: Higher admission serum glucose and admission hyperglycemia are independent predictors of adverse outcomes in ELVO patients treated with MT.

Stroke Mimics and Acute Stroke Evaluation: Clinical Differentiation and Complications after Intravenous Tissue Plasminogen Activator.

BACKGROUND: Intravenous tissue-plasminogen activator remains the only U.S. Food and Drug Administration-approved treatment for acute ischemic stroke. Timely administration of fibrinolysis is balanced with the need for accurate diagnosis. Stroke mimics represent a heterogeneous group of patients presenting with acute-onset focal neurological deficits. If these patients arrive within the extended time window for acute stroke treatment, these stroke mimics may erroneously receive fibrinolytics. OBJECTIVE: This review explores the literature and presents strategies for differentiating stroke mimics. DISCUSSION: Clinical outcome in stroke mimics receiving fibrinolytics is overwhelmingly better than their stroke counterparts. However, the risk of symptomatic intracranial hemorrhage remains a real but rare possibility. Certain presenting complaints and epidemiological risk factors may help differentiate strokes from stroke mimics; however, detection of stroke often depends on presence of posterior vs. anterior circulation strokes. Availability of imaging modalities also assists in diagnosing stroke mimics, with magnetic resonance imaging offering the most sensitivity and specificity. CONCLUSION: Stroke mimics remain a heterogeneous entity that is difficult to identify. All studies in the literature report that stroke mimics treated with intravenous fibrinolysis have better clinical outcome than their stroke counterparts. Although symptomatic intracranial hemorrhage remains a real threat, literature searches have identified only two cases of symptomatic intracranial hemorrhage in stroke mimics treated with fibrinolytics.

Magnesium: potential roles in neurovascular disease.

OBJECTIVE: Magnesium therapy has been studied extensively in pre-clinical and clinical trials in multiple organ systems. Cerebrovascular diseases may benefit from its neuroprotective properties. This review summarizes current studies of magnesium in a wide range of neurovascular diseases. METHODS: We searched relevant terms in the National Library of Medicine PubMed database and selected research including basic science, translational reports, meta-analyses, and clinical studies. RESULTS: Studies examining magnesium administration in ischemic stroke have failed to show any benefit in clinical outcome. Data on magnesium for intracerebral hemorrhage (ICH) are limited. Preliminary investigations in subarachnoid hemorrhage (SAH) were promising, but definitive studies did not reveal differences in clinical outcome between magnesium and placebo-treated groups. Studies examining magnesium administration in global ischemia following cardiac arrest suggest a trend toward improved clinical outcome. The strongest evidence for clinically relevant neuroprotection following magnesium administration derives from studies of pre-term infants and patients undergoing cardiac bypass and carotid endarterectomy procedures. Magnesium was found to have an excellent safety profile across all investigations. CONCLUSION: Magnesium is easy to administer and possesses a favorable safety profile. Its utility as a neuroprotectant in cardiac surgery, carotid endarterectomy, and pre-term infant hypoxia remain promising. Value as a therapeutic agent in ischemic stroke, ICH, and SAH is unclear and appears to be limited by late administration. Ongoing clinical trials assessing magnesium administration in the first hours following symptom onset may help clarify the role of magnesium therapy in these disease processes.

Traumatic fracture of a polymethyl methacrylate patient-specific cranioplasty implant.

OBJECTIVE: To present a case of a traumatic fracture of a polymethyl methacrylate (PMMA) patient-specific implant (PSI) for cranioplasty. METHODS: A 14-year-old boy with a history of right decompressive hemicraniectomy and reconstructive cranioplasty with a PMMA PSI presented after an unhelmeted bicycle accident with somnolence, confusion, seizures, left hemiparesis, and an obviously deformed cranium. RESULTS: Computed tomography scan showed a comminuted, depressed fracture of the implant and cerebral contusions. The implant was seen to be shattered, resulting in displaced, overriding fragments and significant damage to underlying brain. The patient remained neurologically stable. To minimize the number of operations, intervention was delayed while a polyetheretherketone PSI was fabricated. During surgery, it was noted that the fractured pieces of the implant had caused dural lacerations, and some pieces were embedded in brain parenchyma. The fractured PMMA was removed, and the new implant was placed. The patient remained hemiparetic and was later transferred to an inpatient rehabilitation facility. CONCLUSIONS: PMMA PSIs are commonly used for large defects and generally have good outcomes with low rates of revision. The case report described involves a shattered PMMA PSI after a traumatic impact, which resulted in hemiparesis. The question arises if this type of complication can be easily avoided with the addition of titanium onlay to restrict displacement in the event of fracture. This onlay represents a minor change of technique that could prevent migration of fracture fragments.

Guanylin and uroguanylin induce natriuresis in mice lacking guanylyl cyclase-C receptor.

BACKGROUND: Guanylin (GN) and uroguanylin (UGN) are intestinally derived peptide hormones that are similar in structure and activity to the diarrhea-causing Escherichia coli heat-stable enterotoxins (STa). These secretagogues have been shown to affect fluid, Na+, K+, and Cl- transport in both the intestine and kidney, presumably by intracellular cyclic guanosine monophosphate (cGMP)-dependent signal transduction. However, the in vivo consequences of GN, UGN, and STa on renal function and their mechanism of action have yet to be rigorously tested. METHODS: We hypothesized that intravenous administration of GN, UGN, or STa would cause an increase in natriuresis in wild-type mice via cGMP and guanylyl cyclase-C (GC-C, Gucy2c), the only known receptor for these peptide-hormones, and that the peptide-induced natriuresis would be blunted in genetically altered mice devoid of GC-C receptors (GC-C(-/-) null). RESULTS: In wild-type mice using a modified renal clearance model, GN, UGN, and STa elicited significant natriuresis, kaliuresis, and diuresis as well as increased urinary cGMP levels in a time- and dose-dependent fashion. Absolute and fractional urinary sodium excretion levels were greatest approximately 40 minutes following a bolus infusion with pharmacologic doses of these peptides. Unexpectedly, GC-C(-/-) null mice also responded to the GN peptides similarly to that observed in wild-type mice. Glomerular filtration rate (GFR), blood pressure, and plasma cGMP in the mice (wild-type or GC-C(-/-) null) did not significantly vary between the vehicle- and peptide-treatment groups. The effects of UGN may also influence long-term renal function due to down-regulation of the Na+/K+ ATPase gamma-subunit and the Cl- channel ClC-K2 by 60% and 75%, respectively, as assessed by differential display polymerase chain reaction (PCR) (DD-PCR) and Northern blot analysis of kidney mRNA from mice treated with UGN. CONCLUSION: GN, UGN, and STa act on the mouse kidney, in part, through a cGMP-dependent, GC-C-independent mechanism, causing significant natriuresis by renal tubular processes. UGN may have further long-term effects on the kidney by altering the expression of such transport-associated proteins as Na+/K+ ATPase and ClC-K2.