Suboptimal Cerebral Perfusion is Associated with Ischemia After Intracerebral Hemorrhage.

BACKGROUND: Remote ischemic lesions on diffusion-weighted imaging (DWI) occur in one third of patients with intracerebral hemorrhage (ICH) and are associated with worse outcomes. The etiology is unclear and not solely due to blood pressure reduction. We hypothesized that impaired cerebrovascular autoregulation and hypoperfusion below individualized lower limits of autoregulation are associated with the presence of DWI lesions. METHODS: This was a retrospective, single-center study of all primary ICH with intraparenchymal pressure monitoring within 10 days from onset and subsequent magnetic resonance imaging. Pressure reactivity index was calculated as the correlation coefficient between mean arterial pressure and intracranial pressure. Optimal cerebral perfusion pressure (CPPopt) is the cerebral perfusion pressure (CPP) with the lowest corresponding pressure reactivity index. The difference between CPP and CPPopt, time spent below the lower limit of autoregulation (LLA), and time spent above the upper limit of autoregulation (ULA) were calculated by using mean hourly physiologic data. Univariate associations between physiologic parameters and DWI lesions were analyzed by using binary logistic regression. RESULTS: A total of 505 h of artifact-free data from seven patients without DWI lesions and 479 h from six patients with DWI lesions were analyzed. Patients with DWI lesions had higher intracranial pressure (17.50 vs. 10.92 mm Hg; odds ratio 1.14, confidence interval 1.01-1.29) but no difference in mean arterial pressure or CPP compared with patients without DWI lesions. The presence of DWI lesions was significantly associated with a greater percentage of time spent below the LLA (49.85% vs. 14.70%, odds ratio 5.77, confidence interval 1.88-17.75). No significant association was demonstrated between CPPopt, the difference between CPP and CPPopt, ULA, LLA, or time spent above the ULA between groups. CONCLUSIONS: Blood pressure reduction below the LLA is associated with ischemia after acute ICH. Individualized, autoregulation-informed targets for blood pressure reduction may provide a novel paradigm in acute management of ICH and require further study.

Quantification of hematoma and perihematomal edema volumes in intracerebral hemorrhage study: Design considerations in an artificial intelligence validation (QUANTUM) study.

BACKGROUND: Hematoma and perihematomal edema volumes are important radiographic markers in spontaneous intracerebral hemorrhage. Accurate, reliable, and efficient quantification of these volumes will be paramount to their utility as measures of treatment effect in future clinical studies. Both manual and semi-automated quantification methods of hematoma and perihematomal edema volumetry are time-consuming and susceptible to inter-rater variability. Efforts are now underway to develop a fully automated algorithm that can replace them. A (QUANTUM) study to establish inter-quantification method measurement equivalency, which deviates from the traditional use of measures of agreement and a comparison hypothesis testing paradigm to indirectly infer quantification method measurement equivalence, is described in this article. The Quantification of Hematoma and Perihematomal Edema Volumes in Intracerebral Hemorrhage study aims to determine whether a fully automated quantification method and a semi-automated quantification method for quantification of hematoma and perihematomal edema volumes are equivalent to the hematoma and perihematomal edema volumes of the manual quantification method. METHODS/DESIGN: Hematoma and perihematomal edema volumes of supratentorial intracerebral hemorrhage on 252 computed tomography scans will be prospectively quantified in random order by six raters using the fully automated, semi-automated, and manual quantification methods. Primary outcome measures for hematoma and perihematomal edema volumes will be quantified via computed tomography scan on admission (<24 h from symptom onset) and on day 3 (72 ± 12 h from symptom onset), respectively. Equivalence hypothesis testing will be conducted to determine if the hematoma and perihematomal edema volume measurements of the fully automated and semi-automated quantification methods are within 7.5% of the hematoma and perihematomal edema volume measurements of the manual quantification reference method. DISCUSSION: By allowing direct equivalence hypothesis testing, the Quantification of Hematoma and Perihematomal Edema Volumes in Intracerebral Hemorrhage study offers advantages over radiology validation studies which utilize measures of agreement to indirectly infer measurement equivalence and studies which mistakenly try to infer measurement equivalence based on the failure of a comparison two-sided null hypothesis test to reach the significance level for rejection. The equivalence hypothesis testing paradigm applied to artificial intelligence application validation is relatively uncharted and warrants further investigation. The challenges encountered in the design of this study may influence future studies seeking to translate artificial intelligence medical technology into clinical practice.

Bedside quantitative electroencephalography improves assessment of consciousness in comatose subarachnoid hemorrhage patients.

OBJECTIVE: Accurate behavioral assessments of consciousness carry tremendous significance in guiding management, but are extremely challenging in acutely brain-injured patients. We evaluated whether electroencephalography (EEG) and multimodality monitoring parameters may facilitate assessment of consciousness in patients with subarachnoid hemorrhage. METHODS: A retrospective analysis was performed of 83 consecutively treated adults with subarachnoid hemorrhage. All patients were initially comatose and had invasive brain monitoring placed. Behavioral assessments were performed during daily interruption of sedation and categorized into 3 groups based on their best examination as (1) comatose, (2) arousable (eye opening or attending toward a stimulus), and (3) aware (command following). EEG features included spectral power and complexity measures. Comparisons were made using bootstrapping methods and partial least squares regression. RESULTS: We identified 389 artifact-free EEG clips following behavioral assessments. Increasing central gamma, posterior alpha, and diffuse theta-delta oscillations differentiated patients who were arousable from those in coma. Command following was characterized by a further increase in central gamma and posterior alpha, as well as an increase in alpha permutation entropy. These EEG features together with basic neurological examinations (eg, pupillary light reflex) contributed heavily to a linear model predicting behavioral state, whereas brain physiology measures (eg, brain oxygenation), structural injury, and clinical course added less. INTERPRETATION: EEG measures of behavioral states provide distinctive signatures that complement behavioral assessments of patients with subarachnoid hemorrhage shortly after the injury. Our data support the hypothesis that impaired connectivity of cortex with both central thalamus and basal forebrain underlies decreasing levels of consciousness. Ann Neurol 2016;80:541-553.

A quantitative lateral flow assay to detect complement activation in blood.

Complement is a major effector arm of the innate immune system that responds rapidly to pathogens or altered self. The central protein of the system, C3, participates in an amplification loop that can lead to rapid complement deposition on a target and, if excessive, can result in host tissue damage. Currently, complement activation is routinely monitored by assessing total C3 levels, which is an indirect and relatively insensitive method. An alternative approach would be to measure downstream C3 activation products such as C3a and iC3b. However, in vitro activation can produce falsely elevated levels of these biomarkers. To circumvent this issue, a lateral flow immunoassay system was developed that measures iC3b in whole blood, plasma, and serum and avoids in vitro activation by minimizing sample handling. This assay system returns results within 15 min and specifically measures iC3b while having minimal cross-reactivity to other C3 split products. While evaluating the potential of this assay, it was observed that circulating iC3b levels can distinguish healthy individuals from those with complement activation-associated diseases. This tool is engineered to provide an improved method to assess complement activation at point of care and could facilitate studies to monitor disease progression in a variety of inflammatory conditions.

A generalizable physiological model for detection of Delayed Cerebral Ischemia using Federated Learning.

Delayed cerebral ischemia (DCI) is a complication seen in patients with subarachnoid hemorrhage stroke. It is a major predictor of poor outcomes and is detected late. Machine learning models are shown to be useful for early detection, however training such models suffers from small sample sizes due to rarity of the condition. Here we propose a Federated Learning approach to train a DCI classifier across three institutions to overcome challenges of sharing data across hospitals. We developed a framework for federated feature selection and built a federated ensemble classifier. We compared the performance of FL model to that obtained by training separate models at each site. FL significantly improved performance at only two sites. We found that this was due to feature distribution differences across sites. FL improves performance in sites with similar feature distributions, however, FL can worsen performance in sites with heterogeneous distributions. The results highlight both the benefit of FL and the need to assess dataset distribution similarity before conducting FL.

Glioblastoma biomarkers from bench to bedside: advances and challenges.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumour, with few available therapies providing significant improvements in mortality. Biomarkers, which are defined by the National Institutes of Health as 'characteristics that are objectively measured and evaluated as indicators of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention', have the potential to play valuable roles in the diagnosis and treatment of GBM. Although GBM biomarker research is still in its early stages because of the tumour's complex pathophysiology, a number of potential markers have been identified which can be measured in either brain tissue or blood serum. In conjunction with other clinical data, particularly neuroimaging modalities such as MRI, these proteins could contribute to the clinical management of GBM by helping to classify tumours, predict prognosis and assess treatment response. In this article, we review the current understanding of GBM pathophysiology and recent advances in GBM biomarker research, and discuss the potential clinical implications of promising biomarkers. A better understanding of GBM pathophysiology will allow researchers and clinicians to identify optimal biomarkers and methods of interpretation, leading to advances in tumour classification, prognosis prediction and treatment assessment.

Acute ischemic injury on diffusion-weighted magnetic resonance imaging after poor grade subarachnoid hemorrhage.

BACKGROUND: Poor clinical condition is the most important predictor of neurological outcome and mortality after subarachnoid hemorrhage (SAH). Rupture of an intracranial aneurysm was shown to be associated with acute ischemic brain injury in poor grade patients in autopsy studies and small magnetic resonance imaging series. METHODS: We performed diffusion-weighted magnetic resonance imaging (DWI) within 96 h of onset in 21 SAH patients with Hunt-Hess grade 4 or 5 enrolled in the Columbia University SAH Outcomes Project between July 2004 and February 2007. We analyzed demographic, radiological, clinical data, and 3 months outcome. RESULTS: Of the 21 patients 13 were Hunt-Hess grade 5, and eight were grade 4. Eighteen patients (86%) displayed bilateral and symmetric abnormalities on DWI, but not on computed tomography (CT). Involved regions included both anterior cerebral artery territories (16 patients), and less often the thalamus and basal ganglia (4 patients), middle (6 patients) or posterior cerebral artery territories (2 patients), or cerebellum (2 patients). At 1-year, 15 patients were dead (life support had been withdrawn in 6), 2 were moderately to severely disabled (modified Rankin Scale [mRS] = 4-5), and 4 had moderate-to-no disability (mRS = 1-3). CONCLUSIONS: Admission DWI demonstrates multifocal areas of acute ischemic injury in poor grade SAH patients. These ischemic lesions may be related to transient intracranial circulatory arrest, acute vasoconstriction, microcirculatory disturbances, or decreased cerebral perfusion from neurogenic cardiac dysfunction. Ischemic brain injury in poor grade SAH may be a feasible target for acute resuscitation strategies.

Spontaneous hyperventilation and brain tissue hypoxia in patients with severe brain injury.

BACKGROUND: Hyperventilation has been shown to be associated with cerebral vasoconstriction and increased risk of infarction. Our aim was to determine whether spontaneous reduction in end-tidal CO(2) (EtCO(2)) was associated with an increased in brain tissue hypoxia (BTH). METHOD: We studied 21 consecutive patients (mean age 50+/-16 years; 15 women) undergoing continuous monitoring for brain tissue oxygenation (PbtO(2)), intracranial pressure (ICP), cerebral perfusion pressure (CPP) and EtCO(2); mean values were recorded hourly BTH was defined as brain tissue oxygen tension (PbtO(2)) <15 mm Hg. RESULTS: Diagnoses included subarachnoid haemorrhage (67%), intracranial haemorrhage (24%) and traumatic brain injury (10%). Overall, BTH occurred during 22.5% of the study period (490/2179 hourly data). The frequency of BTH increased progressively from 15.7% in patients with normal EtCO(2) (35-44 mm Hg) to 33.9% in patients with EtCO(2)<25 mm Hg (p<0.001). The mean tidal volume and minute ventilation were 7+/-2 ml/kg and 9+/-2 1/min, respectively. Hypocapnia was associated with higher measured-than-set respiratory rates and maximal minute ventilation values, suggestive of spontaneous hyperventilation. Using a generalised estimated equation (GEE) and after adjustment for GCS, ICP and core temperature, the variables independently associated with BTH events were EtCO(2) (OR: 0.94; 95% CI 0.90 to 0.97; p<0.001) and CPP (OR: 0.98; 95% CI 0.97 to 0.99; p=0.004). CONCLUSION: The risk of brain tissue hypoxia in critically brain-injured patients increases when EtCO(2) values are reduced. Unintentional spontaneous hyperventilation may be a common and under-recognised cause of brain tissue hypoxia after severe brain injury.

Clinical grading scales in intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) carries higher risk of long-term disability and mortality than any other form of stroke. Despite greater understanding of ICH pathophysiology, treatment options for this devastating condition remain limited. Moreover, a lack of a standard, universally accepted clinical grading scale for ICH has contributed to variations in management protocols and clinical trial designs. Grading scales are essential for standardized assessment and communication among physicians, selecting optimized treatment regiments, and designing effective clinical trials. There currently exist a number of ICH grading scales and prognostic models that have been developed for mortality and/or functional outcome, particularly 30 days after the ICH onset. Numerous reliable scales have been externally validated in heterogeneous populations. We extensively reviewed the inherent strengths and limitations of all the existing clinical ICH grading scales based on their development and validation methodology. For all ICH grading scales, we carefully observed study design and the definition and timing of outcome assessment to elucidate inconsistencies in grading scale derivation and application. Ultimately, we call for an expansive, prospective, multi-center clinical outcome study to clearly define all aspects of ICH, establish ideal grading scales, and standardized management protocols to enable the identification of novel and effective therapies in ICH.

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. Outcomes were assessed by the modified Rankin scale (mRS). Analysis of variance and the Chi-square test were used to guide an analysis of GCS breakpoints according to outcomes. Multivariable logistic regression analysis was used to assess the ability of the Hunt and Hess, GCS, World Federation of Neurological Surgeons Grading Scale, and the PGS to predict long-term outcome. Outcome analysis revealed significant breakpoints in admission GCS scores: PGS-A (GCS 10-12); PGS-B (GCS 8-9); PGS-C (GCS 5-7); PGS-D (GCS 3-4) (p<0.001). In surgical patients, 95.2% of PGS-A, 58.1% of PGS-B, 35.4% of PGS-C, and 28.6% of PGS-D had a favorable one-year outcome. When controlling for age, sex, and operation status, PGS was the only scale predictive of long-term outcome. The odds ratios (OR) for unfavorable outcome according to PGS admission scores (with PGS-A as the reference) were: PGS-B, OR=14.2 (95% CI 1.5-140.5); PGS-C, OR=38.5 (95% CI 4.2-340.0); and PGS-D, OR=63.4 (95% CI 5.6-707.1). In addition to PGS admission scores, an age of 70 or greater was a significant predictor of poor outcome with an OR of 7.5 (95% CI 1.8-30.7). No patients with a PGS-C or PGS-D over the age of 70 had a favorable long-term outcome. Therefore, elements of the Hunt and Hess and GCS can be combined into the PGS to predict long-term outcome in poor grade aSAH patients. However, patients with PGS-C and PGS-D over the age of 70 should be assessed carefully prior to definitive treatment.

Elevation of monocyte chemoattractant protein-1 in patients experiencing neurocognitive decline following carotid endarterectomy.

BACKGROUND: Previous studies have demonstrated that elevated pre-operative monocyte count is an independent predictor of acute neurocognitive decline following carotid endarterectomy (CEA). Monocyte chemoattractant protein-1 (MCP-1), secreted by human endothelial and monocyte-like cells, is a potent mediator of inflammation and mononuclear cell trafficking. This study examines the relationship between peri-operative serum MCP-1 elevation and post-operative neurocognitive injury following CEA. METHODS: Fifty-two patients undergoing CEA and 67 lumbar laminectomy (LL) controls were administered a battery of five neuropsychological tests pre-operatively and on post-operative day 1 (POD 1). Change in individual test scores from baseline to POD 1 were converted into Z-score and used to develop a point system quantifying the degree of neurocognitive dysfunction relative to change within the LL group. Neurocognitive injury following CEA was defined as a score greater than 2 standard deviations above mean total deficit scores of LL controls. Serum MCP-1 levels were measured pre-operatively and on POD 1 by enzyme-linked immunosorbent assay. FINDINGS: Mean percent MCP-1 elevation was higher for the 13 injured CEA patients (147.7 +/- 32.4%) in our cohort compared to 39 age- and sex-matched uninjured CEA patients (76.0 +/- 16.5%). In unconditional multivariate logistic regression analysis, percent elevation in serum MCP-1 level was associated with neurocognitive injury one day after CEA (OR = 2.19, 95% CI = 1.13-4.26, P = 0.021, for a 100% elevation from pre-operative levels). CONCLUSIONS: Peri-operative elevations in serum MCP-1 levels correlate with acute neurocognitive dysfunction following CEA. These data implicate an inflammatory mechanism in the pathogenesis of Ischaemic neurocognitive decline.

Topical vancomycin to reduce surgical-site infections in neurosurgery: Study protocol for a multi-center, randomized controlled trial.

Surgical-site infections (SSIs) account for 20% of all healthcare-associated infections, are the most common nosocomial infection among surgical patients, and are a focus of quality improvement initiatives. Despite implementation of many quality care measures (e.g. prophylactic antibiotics), SSIs remain a significant cause of morbidity, mortality, and economic burden, particularly in the field of neurosurgery. Topical vancomycin is increasingly utilized in instrumented spinal and cardiothoracic procedures, where it has been shown to reduce the risk of SSIs. However, a randomized controlled trial assessing its efficacy in the general neurosurgical population has yet to be done. The principle aim of "Topical Vancomycin for Neurosurgery Wound Prophylaxis" (NCT02284126) is to determine whether prophylactic, topical vancomycin reduces the risk of SSIs in the adult neurosurgical population. This prospective, multicenter, patient-blinded, randomized controlled trial will enroll patients to receive the standard of care plus topical vancomycin, or the standard of care alone. The primary endpoint of this study is a SSI by postoperative day (POD) 30. Patients must be over 18years of age. Patients are excluded for renal insufficiency, vancomycin allergy, and some ineligible procedures. Univariate analysis and logistic regression will determine the effect of topical vancomycin on SSIs at 30days. A randomized controlled trial is needed to determine the efficacy of this treatment. Results of this trial are expected to directly influence the standard of care and prevention of SSIs in neurosurgical patients.

Hemicraniectomy for malignant middle cerebral artery territory infarction: an updated review.

A decompressive hemicraniectomy is frequently performed for patients with malignant middle cerebral artery territory infarction (MMI) to reduce the intracranial hypertension, which may otherwise result in transtentorial herniation. However, certain clinically significant issues ­ diagnostic criteria, predictors of the MMI clinical course, benefit of surgery in certain populations, timing of surgery ­ are unresolved. In this article, we provide an updated review on the diagnosis and management of MMI. An extensive search of the PubMed, EMBASE, and Cochrane was conducted using varying combinations of the search terms, "hemicraniectomy," "decompressive craniectomy," "malignant middle cerebral artery territory infarction," "massive middle cerebral artery territory infarction," "massive ischemic stroke," "decompressive surgery," and "neurosurgery for ischemic stroke." Several large, randomized trials within the past decade have firmly established the benefit of decompressive hemicraniectomy (DHC) as a treatment of MMI. Further studies since then have not only better characterized the diagnosis and predictors of MMI, but have also shown that this benefit extends to patients with additional clinical and demographic characteristics. Future randomized studies should continue to evaluate the benefit of a DHC in other subgroups, and assess neurocognitive and psychosocial secondary outcomes.

Pathological mechanisms underlying aneurysmal subarachnoid haemorrhage and vasospasm.

Aneurysmal subarachnoid haemorrhage is a cerebrovascular disease associated with an overall mortality as high as 50%. Delayed ischaemic neurologic deficits are a major contributor to this statistic, as well as the significant morbidity associated with the disease. Studies examining the pathophysiologic events causing these devastating changes in cerebral blood flow have identified several mechanisms which are thought to contribute to the development of delayed ischaemic neurological deficits, perhaps the most damaging of which are increased intracranial pressure and cerebral vasospasm. In addition, the presence of blood in the subarachnoid space can trigger a myriad of reactions resulting in increased capillary permeability, breakdown of the blood-brain barrier, and inflammation in surrounding neural tissue that adds to the devastating effects of haemorrhage. A detailed understanding of the post-haemorrhagic cellular and molecular changes that contribute to the development of cerebral ischaemia and vasospasm is imperative to the formulation of treatment and prevention options for subarachnoid haemorrhage patients. Despite a large body of research within this field, a complete understanding of rupture and vasospasm remains elusive. This study reviews the role of vasoactive substances, such as endothelin-1, as well as the histochemistry and molecular pathology of post-haemorrhage inflammation in the development of vasospasm and cerebral ischaemia.

The role of age in intracerebral hemorrhages.

We aimed to identify the role of age in intracerebral hemorrhage (ICH), as well as characterize the most commonly used age cut off points in the literature, with the hope of understanding and guiding treatment. Strokes are one of the leading causes of death in the USA, and ICH is the deadliest type. Age is a strong risk factor, but it also affects the body in numerous ways, including changes to the cardiovascular and central nervous systems that interplay with the multiple risk factors for ICH. Understanding the role of age in risk and outcomes of ICH can guide treatment and future clinical trials. A current review of the literature suggests that the age cut offs for increased rates of mortality and morbidity vary from 60-80 years of age, with the most common age cut offs being at 65 or 70 years of age. In addition to age as a determinant of ICH outcomes, age has its own effects on the maturing body in terms of changes in physiology, while also increasing the risk of multiple chronic health conditions and comorbidities, including hypertension, diabetes, and anticoagulant treatment for atrial fibrillation, all of which contribute to the pathology of ICH. The interaction of these chronic conditions, changes in physiology, age, and ICH is evident. However, the exact mechanism and extent of the impacts remains unclear. The ambiguity of these connections may be further obscured by individual patient preferences, and there are limitations in the literature which guides the current recommendations for aging patients.

Underlying effect of age on outcome differences in arteriovenous malformation-associated intracerebral hemorrhage.

Brain arteriovenous malformations (AVM) are the most common cause of intracerebral hemorrhage (ICH) in young adults. Although previous studies have found that the mortality and morbidity of ICH due to AVM (AVM-ICH) is lower than in spontaneous ICH, it is unclear whether the more favorable prognosis is directly related to the presence of the vascular malformation. We included 34 patients with AVM-ICH and 187 with spontaneous intracerebral hemorrhage (sICH) due to either hypertension or cerebral amyloid angiopathy. Patient data were obtained from the prospective Intracerebral Hemorrhage Outcomes Project, which enrolls ICH patients admitted to Columbia University Medical Center. Using ICH etiology (AVM-ICH or sICH) and previously verified predictors of ICH outcome, two multivariate analyses were performed with and without age to compare the odds of death at 3 months and the functional outcome. Although mortality in AVM-ICH group was lower than the sICH group (20.6% versus 43.3%, respectively), this value was only significant when age was excluded (p=0.017) and lost its significance when we controlled for age (p=0.157). There was an analogous loss of significance with functional outcome using the modified Rankin Scale. In conclusion, our data suggests that the previously observed lower case fatality rate and more favorable functional outcomes in the AVM-ICH group compared to the sICH group may largely be the result of age.

Treatment of mechanically-induced vasospasm of the carotid artery in a primate using intra-arterial verapamil: a technical case report.

BACKGROUND: Despite improvements in the safety and efficacy of endovascular procedures, considerable morbidity may still be attributed to vasospasm. Vasospasm has proven amenable to pharmacological intervention such as nitrates, intravenous calcium channel blockers (CCBs), and intra-arterial papaverine, particularly in small vessels. However, few studies have focused on medium to large vessel spasm. Here we report the use of an intra-arterial CCB, verapamil, to treat flow-limiting mechanically-induced spasm of the common carotid artery (CCA) in a primate. We believe this to be the first such report of its kind. CASE PRESENTATION: As part of a study assessing the placement feasibility and safety of a catheter capable of delivering intra-arterial cerebroprotective therapy, a female 16 kg baboon prophylaxed with intravenous nitroglycerin underwent transfemoral CCA catheterization with a metallic 6-Fr catheter without signs of acute spasm. The protocol dictated that the catheter remain in the CCA for 12 hours. Upon completion of the protocol, arteriography revealed a marked decrease in CCA size (mean cross-sectional area reduction = 31.6 +/- 1.9%) localized along the catheter length. Intra-arterial verapamil (2 mg/2cc) was injected and arteriography was performed 10 minutes later. Image analysis at 6 points along the CCA revealed a 21.0 +/- 1.7% mean increase in vessel diameter along the length of the catheter corresponding to a 46.7 +/- 4.0% mean increase in cross-sectional area. Mean systemic blood pressure did not deviate more than 10 mm Hg during the procedure. CONCLUSIONS: Intraluminal CCBs like verapamil may constitute an effective endovascular treatment for mechanically-induced vasospasm in medium to large-sized vessels such as the CCA.

Reduced middle cerebral artery velocity during cross-clamp predicts cognitive dysfunction after carotid endarterectomy.

Transcranial Doppler (TCD) is a useful monitor that can be utilized during carotid endarterectomy (CEA). Cognitive dysfunction is a subtler and more common form of neurologic injury than stroke. We aimed to determine whether reduced middle cerebral artery (MCA) mean velocity (MV) predicts cognitive dysfunction and if so, whether a threshold of increased risk of cognitive dysfunction can be identified. One hundred twenty-four CEA patients were included in this observational study and neuropsychometrically evaluated preoperatively and 24 hours postoperatively. MCA-MV was measured by TCD and percentage of baseline during cross-clamp was calculated (MV(cross-clamp)/MV(baseline)). Patients with cognitive dysfunction had significantly lower MV during cross-clamp than those without cognitive dysfunction (33.1 ± 13.7 cm/s versus 39.6 ± 16.0 cm/s, p=0.02). In the final multivariate model, each percent reduction in MV was significantly associated with greater risk of cognitive dysfunction (odds ratio [OR]: 0.05 [95% confidence interval {CI} 0.01-0.23], p < 0.001) while statin use was associated with lower risk (OR: 0.33 [95% CI 0.12-0.92], p = 0.03). Using receiver operator characteristic curve analysis, the Youden index identified 72% of baseline MV during cross-clamp as the cutoff of maximum discrimination. Significantly more patients with MV < 72% of baseline during cross-clamp exhibited cognitive dysfunction than patients with MV ≥ 72% of baseline (74.1% versus 27.1%, p < 0.001). Reduced MCA-MV during cross-clamp is a predictor of cognitive dysfunction exhibited 24 hours after CEA. MCA-MV reduced to <72% of baseline, or a ≥28% reduction from baseline, is the threshold most strongly associated with increased risk of cognitive dysfunction. These observations should be considered by all clinicians that utilize intraoperative monitoring for CEA.

The role of vascular remodeling and inflammation in the pathogenesis of intracranial aneurysms.

While the mechanisms triggering pathogenesis of intracranial aneurysms have not been fully elucidated, different mechanisms have been proposed ranging from hemodynamic mechanisms to genetic predispositions. One mechanism that has been thoroughly explored is the physiological and pathological vascular remodeling that occurs in conjunction with inflammatory reactions resulting in the initiation and progression of these lesions. Both hemodynamic stimuli and vascular inflammation can trigger a series of biochemical reactions resulting in vascular smooth muscle cell apoptosis and migration causing thinned, dilated areas of the cerebral vasculature. In addition, an imbalance between extracellular matrix remodeling proteins, such as matrix metalloproteinases and their inhibitors, can result in accelerated degradation of the internal elastic lamina and the adventitial layers, further weakening the vessel. While these processes occur under normal physiological conditions, situations that alter their balance such as inflammation caused by cigarette smoking or cocaine usage or hypoxia induced under chronic hypertensive conditions can alter the delicate balance of these reactions potentiating pathological remodeling and aneurysm development. The present study represents a thorough literature review of the vascular remodeling and inflammatory components to aneurysmal pathogenesis.

The quantified patient: a patient participatory culture.

The Quantified Self Movement, which aims to improve various aspects of life and health through recording and reviewing daily activities and biometrics, is a new and upcoming practice of self monitoring that holds much promise. Now, the most underutilized resource in ambulatory health care, the patient, can participate like never before, and the patient's Quantified Self can be directly monitored and remotely accessed by health care professionals.