A Standardized Approach to Treatment Over Objection in Patients Lacking Decision-Making Capacity Secondary to Neurologic Disease.

Neurologic diseases, ranging from Alzheimer dementia to mass lesions in the frontal lobe, may impair decision making. When patients with neurologic disease lack decision-making capacity, but refuse treatment, should they be treated over their objection? To address this type of ethical dilemma in medical illness, Rubin and Prager developed a standardized 7-question approach: (1) How imminent is harm without intervention? (2) What is the likely severity of harm without intervention? (3) What are the risks of intervention? (4) What are the logistics of treating over objection? (5) What is the efficacy of the proposed intervention? (6) What is the likely emotional effect of a coerced intervention? (7) What is the patient's reason for refusal? We describe the application of the standardized Rubin/Prager approach as a checklist to the case of a 50-year-old woman with a large frontal lobe meningioma, who lacked capacity as a result of the meningioma, but refused surgery. This approach may be applied to similar ethical dilemmas of treatment over objection in patients lacking capacity as a result of neurologic disease.

A 53-year-old woman with a rapidly progressive, non-enhancing left frontotemporal lesion.

Fifty-three-year-old woman presented with chronic, episodic headache.

Deconvolution of cell type-specific drug responses in human tumor tissue with single-cell RNA-seq.

Background: Preclinical studies require models that recapitulate the cellular diversity of human tumors and provide insight into the drug sensitivities of specific cellular populations. The ideal platform would enable rapid screening of cell type-specific drug sensitivities directly in patient tumor tissue and reveal strategies to overcome intratumoral heterogeneity.

Methods: We combine multiplexed drug perturbation in acute slice culture from freshly resected tumors with single-cell RNA sequencing (scRNA-seq) to profile transcriptome-wide drug responses in individual patients.

Endoscopic Petrous Apex Surgery: The Utilization of Frontal Sinus Instrumentation.

Background: The petrous apex is a complex anatomic region for which each surgical approach each has distinct limitations. The authors describe the use of frontal sinus instrumentation for the endonasal endoscopic approach to petrous apex lesions OBJECTIVE:: To demonstrate that the angled design of frontal sinus instrumentation has pronounced clinical utility for the transsphenoidal transclival approach to the petrous apex.

Methods: The authors present cases of expansile petrous apex lesions approached endoscopically via transsphenoid and transclival corridors, and highlight the technique of using curved frontal sinus instruments and angled endoscopes for posterolateral reach in the petrous apex dissection.

Pediatric sinonasal and skull base lesions.

Pediatric skull base lesions are complex and challenging disorders. Safe and comprehensive management of this diverse group of disorders requires the expertise of an experienced multidisciplinary skull base team. Adult endoscopic skull base surgery has evolved due to technologic and surgical advancements, multidisciplinary team approaches, and continued innovation.

Near real-time intraoperative brain tumor diagnosis using stimulated Raman histology and deep neural networks.

Intraoperative diagnosis is essential for providing safe and effective care during cancer surgery. The existing workflow for intraoperative diagnosis based on hematoxylin and eosin staining of processed tissue is time, resource and labor intensive. Moreover, interpretation of intraoperative histologic images is dependent on a contracting, unevenly distributed, pathology workforce.

Transoral Finger-Retraction for Endonasal Endoscopic Resection of Masseteric and Buccal Space Lesions.

Lesions involving the masseteric and buccal spaces have traditionally required transoral or transcervical approaches. Herein, the authors describe the successful endonasal endoscopic resection of a juvenile nasopharyngeal angiofibroma (JNA) with significant extension into the masseteric and buccal spaces facilitated by transoral finger retraction. Juvenile nasopharyngeal angiofibromas are hypervascular tumors originating in the pterygopalatine fossa (PPF) with complex relationships to skull base and orbital structures.

Extent of BOLD Vascular Dysregulation Is Greater in Diffuse Gliomas without Isocitrate Dehydrogenase 1 R132H Mutation.

Purpose To determine the effect that R132H mutation status of diffuse glioma has on extent of vascular dysregulation and extent of residual blood oxygen level-dependent (BOLD) abnormality after surgical resection. Materials and Methods This study was an institutional review board-approved retrospective analysis of an institutional database of patients, and informed consent was waived. From 2010 to 2017, 39 treatment-naïve patients with diffuse glioma underwent preoperative echo-planar imaging and BOLD functional magnetic resonance imaging.

Direct, intraoperative observation of ~0.1 Hz hemodynamic oscillations in awake human cortex: implications for fMRI.

An almost sinusoidal, large amplitude ~0.1 Hz oscillation in cortical hemodynamics has been repeatedly observed in species ranging from mice to humans. However, the occurrence of 'slow sinusoidal hemodynamic oscillations' (SSHOs) in human functional magnetic resonance imaging (fMRI) studies is rarely noted or considered.

Complement inhibition promotes endogenous neurogenesis and sustained anti-inflammatory neuroprotection following reperfused stroke.

Background And Purpose: The restoration of blood-flow following cerebral ischemia incites a series of deleterious cascades that exacerbate neuronal injury. Pharmacologic inhibition of the C3a-receptor ameliorates cerebral injury by attenuating post-ischemic inflammation. Recent reports also implicate C3a in the modulation of tissue repair, suggesting that complement may influence both injury and recovery at later post-ischemic time-points.

Motor deficits correlate with resting state motor network connectivity in patients with brain tumours.

While a tumour in or abutting primary motor cortex leads to motor weakness, how tumours elsewhere in the frontal or parietal lobes affect functional connectivity in a weak patient is less clear. We hypothesized that diminished functional connectivity in a distributed network of motor centres would correlate with motor weakness in subjects with brain masses. Furthermore, we hypothesized that interhemispheric connections would be most vulnerable to subtle disruptions in functional connectivity.

Intranasal delivery of caspase-9 inhibitor reduces caspase-6-dependent axon/neuron loss and improves neurological function after stroke.

Despite extensive research to develop an effective neuroprotective strategy for the treatment of ischemic stroke, therapeutic options remain limited. Although caspase-dependent death is thought to play a prominent role in neuronal injury, direct evidence of active initiator caspases in stroke and the functional relevance of this activity have not previously been shown. Using an unbiased caspase-trapping technique in vivo, we isolated active caspase-9 from ischemic rat brain within 1 h of reperfusion.

Systemic expression of matrix metalloproteinase-9 in patients with cerebral arteriovenous malformations.

Objective: Increased expression angiogenic factors, such as matrix metalloproteinases (MMPs), are associated with the formation of cerebral arteriovenous malformations (AVMs). The objective of this study was to determine plasma levels of MMP-9 of patients with AVMs.

Methods: Blood samples were drawn from 15 patients with AVMs before treatment, 24 hours postembolization, 24 hours postresection, and 30 days postresection.

Treatment guidelines for cerebral arteriovenous malformation microsurgery.

The goal of cerebral arteriovenous malformation (AVM) treatment is to eliminate intracerebral hemorrhage risk and to preserve or maximize neurological functions of the patient. Interventional planning must determine the modality or combination of modalities with the greatest success rate according to patient characteristics, AVM architecture, and the capabilities of the treatment option to fulfill the goals of treatment. Although there is a lack of data from randomized trials to guide AVM management, microsurgery is a mainstay of therapy in patients receiving definitive intervention.

Elevated troponin levels are predictive of mortality in surgical intracerebral hemorrhage patients.

Objective: Elevated troponin levels are a common occurrence after ischemic stroke and subarachnoid hemorrhage (SAH), and have been described as a neurogenic form of myocardial injury. The prognostic significance of this event is controversial with numerous studies citing conflicting results. The importance of cardiac stress is of particular relevance in the operative management of intracerebral hemorrhage (ICH).

The complement cascade: new avenues in stroke therapy.

Recent evidence has shown that after the initial occlusion, a large portion of stroke patients achieve some degree of reperfusion either through collateral circulation or clot dissolution. However, it appears that this reperfusion may lead to increased inflammation-induced damage. Even though the exact mechanism of this secondary injury is unclear, several experimental studies have indicated an intimate connection between complement and this secondary form of damage.

Adjuvant embolization with N-butyl cyanoacrylate in the treatment of cerebral arteriovenous malformations: outcomes, complications, and predictors of neurologic deficits.

Background And Purpose: The purpose of this study was to assess the frequency, severity, and predictors of neurological deficits after adjuvant embolization for cerebral arteriovenous malformations.

Methods: From 1997 to 2006, 202 of 275 patients with arteriovenous malformation received embolization before microsurgery (n=176) or radiosurgery (n=26). Patients were examined before and after endovascular embolization and at clinical follow-up (mean, 43.

Synergistic neuroprotective effects of C3a and C5a receptor blockade following intracerebral hemorrhage.

Background: Intracerebral hemorrhage (ICH) is associated with neurological injury that may be ameliorated by a neuroprotective strategy targeting the complement cascade. We investigated the role of C5a-receptor antagonist (C5aRA) solely and in combination with C3a-receptor antagonist (C3aRA) following ICH in mice.

Methods: Adult male C57BL/6J mice were randomized to receive vehicle, C5aRA alone or C3aRA and C5aRA 6 and 12 h after ICH, and every 12 h thereafter.

Evaluation of a revised Glasgow Coma Score scale in predicting long-term outcome of poor grade aneurysmal subarachnoid hemorrhage patients.

Although many scales attempt to predict outcome following aneurysmal subarachnoid hemorrhage (aSAH), none have achieved universal acceptance, and most scales in common use are not statistically derived. We propose a statistically validated scale for poor grade aSAH patients that combines the Hunt and Hess grades and the Glasgow Coma Scale (GCS) scores; we refer to this as the Poor Grade GCS (PGS). The GCS scores of 160 poor grade aSAH patients (Hunt and Hess Grades 4 and 5) were recorded throughout their hospital stay.

Clinical features, surgical treatment, and long-term outcome in adult patients with moyamoya disease. Clinical article.

Object: The object of this study was to report the clinical features, surgical treatment, and long-term outcomes in adults with moyamoya phenomenon treated at a single institution in the US.

Methods: Forty-three adult patients with moyamoya disease (mean age 40 +/- 11 years [SD], range 18-69 years) were treated with encephaloduroarteriosynangiosis (EDAS). Neurologists examined patients pre- and postoperatively.

Predictors of seizure onset after intracerebral hemorrhage and the role of long-term antiepileptic therapy.

Objective: Seizures are a common complication after hemorrhagic stroke that may slow recovery and decrease quality of life. Recent evidence suggests that early- and late-onset seizures have distinct etiologies, rendering the role of prophylactic long-term antiepileptic drugs controversial. We investigated predictors of early- and late-onset seizures after evacuation of intracerebral hemorrhage (ICH) in an attempt to guide antiepileptic drug management in this patient population.

The role of polyamine metabolism in neuronal injury following cerebral ischemia.

Stroke is a leading cause of morbidity and mortality in the US, with secondary damage following the initial insult contributing significantly to overall poor outcome. Prior investigations have shown that the metabolism of certain polyamines such as spermine, spermidine, and putrescine are elevated in ischemic parenchyma, resulting in an increase in their metabolite concentration. Polyamine metabolites tend to be cytotoxic, leading to neuronal injury in the penumbra following stroke and expansion of the area of infarcted tissue.

Efficacy of lamina terminalis fenestration in reducing shunt-dependent hydrocephalus following aneurysmal subarachnoid hemorrhage: a systematic review. Clinical article.

Object: Chronic hydrocephalus requiring shunt placement is a common complication following aneurysmal subarachnoid hemorrhage (SAH). Controversy exists over whether microsurgical fenestration of the lamina terminalis during aneurysm surgery affords a reduction in the development of shunt-dependent hydrocephalus. To resolve this debate, the authors performed a systematic review and quantitative analysis of the literature to determine the efficacy of lamina terminalis fenestration in reducing aneurysmal SAH-associated shunt-dependent hydrocephalus.

The efficacy of direct extracranial-intracranial bypass in the treatment of symptomatic hemodynamic failure secondary to athero-occlusive disease: a systematic review.

Objective: The 1985 International Extracranial-Intracranial (EC-IC) Bypass Trial failed to show a benefit following surgery in patients with varying degrees of angiographic ICA stenosis. More recent studies using modern technology to identify appropriate candidates, however, have generated promising findings. As a result, controversy exists regarding the role of this technique in the treatment of symptomatic athero-occlusive disease.

The role of indirect extracranial-intracranial bypass in the treatment of symptomatic intracranial atheroocclusive disease.

Object: The optimal treatment of medically refractory intracranial atheroocclusive disease remains unclear. The EC-IC Bypass Study Investigators found that patients with internal carotid and middle cerebral artery (ICA and MCA) occlusion received no benefit from direct superficial temporal artery to MCA bypass, and that patients with ICA occlusion and MCA stenosis may have actually fared worse after surgery, perhaps in part due to flow reversal in critical perforator-bearing segments. Although the results of recent investigations have suggested that direct bypass may be beneficial in a subgroup of patients with hemodynamic failure secondary to unilateral ICA occlusion, similar data do not exist for patients with hemodynamic failure from other intracranial stenoocclusive diseases.