Nicolas K. Khattar

Systolic Blood Pressure Within 24 Hours After Thrombectomy for Acute Ischemic Stroke Correlates With Outcome

Background Current guidelines suggest treating blood pressure above 180/105 mm Hg during the first 24 hours in patients with acute ischemic stroke undergoing any form of recanalization therapy. Currently, no studies exist to guide blood pressure management in patients with stroke treated specifically with mechanical thrombectomy. We aimed to determine the association between blood pressure parameters within the first 24 hours after mechanical thrombectomy and patient outcomes. Methods and Results We retrospectively studied a consecutive sample of adult patients who underwent mechanical thrombectomy for acute ischemic stroke of the anterior cerebral circulation at 3 institutions from March 2015 to October 2016. We collected the values of maximum, minimum, and average values of systolic blood pressure, diastolic blood pressure, and mean arterial pressures in the first 24 hours after mechanical thrombectomy. Primary and secondary outcomes were patients’ functional status at 90 days measured on the modified Rankin scale and the incidence and severity of intracranial hemorrhages within 48 hours. Associations were explored using an ordered multivariable logistic regression analyses. A total of 228 patients were included (mean age 65.8±14.3; 104 males, 45.6%). Maximum systolic blood pressure independently correlated with a worse 90‐day modified Rankin scale and hemorrhagic complications within 48 hours (adjusted odds ratio=1.02 [1.01–1.03], P=0.004; 1.02 [1.01–1.04], P=0.002; respectively) in multivariable analyses, after adjusting for several possible confounders. Conclusions Higher peak values of systolic blood pressure independently correlated with worse 90‐day modified Rankin scale and a higher rate of hemorrhagic complications. Further prospective studies are warranted to identify whether systolic blood pressure is a therapeutic target to improve outcomes.

Continuous infusion of low-dose unfractionated heparin after aneurysmal subarachnoid hemorrhage: a preliminary study of cognitive outcomes

OBJECTIVECognitive dysfunction occurs in up to 70% of aneurysmal subarachnoid hemorrhage (aSAH) survivors. Low-dose intravenous heparin (LDIVH) infusion using the Maryland protocol was recently shown to reduce clinical vasospasm and vasospasm-related infarction. In this study, the Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive changes in aSAH patients treated with the Maryland LDIVH protocol compared with controls.METHODSA retrospective analysis of all patients treated for aSAH between July 2009 and April 2014 was conducted. Beginning in 2012, aSAH patients were treated with LDIVH in the postprocedural period. The MoCA was administered to all aSAH survivors prospectively during routine follow-up visits, at least 3 months after aSAH, by trained staff blinded to treatment status. Mean MoCA scores were compared between groups, and regression analyses were performed for relevant factors.RESULTSNo significant differences in baseline characteristics were observed between groups. The mean MoCA score for the LDIVH group (n = 25) was 26.4 compared with 22.7 in controls (n = 22) (p = 0.013). Serious cognitive impairment (MoCA ≤ 20) was observed in 32% of controls compared with 0% in the LDIVH group (p = 0.008). Linear regression analysis demonstrated that only LDIVH was associated with a positive influence on MoCA scores (β = 3.68, p =0.019), whereas anterior communicating artery aneurysms and fevers were negatively associated with MoCA scores. Multivariable linear regression analysis resulted in all 3 factors maintaining significance. There were no treatment complications.CONCLUSIONSThis preliminary study suggests that the Maryland LDIVH protocol may improve cognitive outcomes in aSAH patients. A randomized controlled trial is needed to determine the safety and potential benefit of unfractionated heparin in aSAH patients.

Basic Endovascular Techniques: Direct, Balloon-Assisted, and Stent-Assisted Coil Embolization

Abstract Devices and techniques for the endovascular treatment of intracranial aneurysms have rapidly progressed since their clinical debut nearly three decades ago. However, mastery of basic embolization techniques remains the cornerstone of successful endovascular therapy. Commonly employed techniques include direct, balloon-assisted, and stent-assisted coil embolization. The neuroendovascular field continues to innovate and coil embolization may not remain at the forefront of endovascular aneurysm treatment in the future. The introduction of innovative and promising new devices that do not utilize a coil platform may diminish the future importance of coil embolization techniques leading to a new age in aneurysm embolization where the coil is no longer the dominant device. In this chapter, we will discuss the basics of coil embolization focusing on standard direct, balloon-assisted, and stent-assisted techniques as they remain the workhorse options for aneurysm embolization.

Delayed Neurological Injury Not From Large-Vessel Vasospasm

Abstract Delayed neurological injury in patients with aneurysmal subarachnoid hemorrhage has long been attributed to large-vessel vasospasm. New evidence suggests that delayed neurological injury is correlated to other pathophysiological mechanisms. Neuroinflammation is considered a hallmark feature of subarachnoid hemorrhage and is associated with release of various inflammatory molecules, believed to contribute to continued neurological injury and associated cognitive decline. Cortical spreading depolarization is an additional mechanism that could be causing microvascular ischemia and additional injury. Another cause of delayed injury associated with aneurysmal subarachnoid hemorrhage is hydrocephalus, usually treated with cerebrospinal fluid diversion. Various therapeutic interventions have been designed to target delayed injury. Unfractionated heparin, glyburide, IL-1 antagonists as well as TLR-4 antagonists target delayed neurological injury by blocking inflammatory pathways associated with long-term outcomes.

Neurocognitive outcomes after aneurysmal subarachnoid hemorrhage: Identifying inflammatory biomarkers

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe type of stroke which carries a high case-fatality rate. Those who survive the ictus of aneurysm rupture harbor substantial risks of neurological morbidity, functional disability, and cognitive dysfunction. Although the pervasiveness of cognitive impairment is widely acknowledged as a long-term sequela of aSAH, the mechanisms underlying its development are poorly understood. The onset of aSAH elicits activation of the inflammatory cascade, and ongoing neuroinflammation is suspected to contribute to secondary complications, such as vasospasm and delayed cerebral ischemia. In this review, we analyze the extant literature regarding the relationship between neuroinflammation and cognitive dysfunction after aSAH. Pro-inflammatory cytokines appear to play a role in maintaining normal cognitive function in adults unaffected by aSAH. However, in the setting of aSAH, elevated cytokine levels may correlate with worse neuropsychological outcomes. This seemingly dichotomous relationship between neuroinflammation and cognition suggests that the action of cytokines varies, depending on their physiologic environment. Experimental therapies which suppress the immune response to aSAH appear to have a beneficial effect on cognitive outcomes. However, further studies are necessary to determine the utility of inflammatory mediators as biomarkers of neurocognitive outcomes, as well as their role in the management of aSAH.

Chapter 21 – Basic Endovascular Techniques: Direct, Balloon-Assisted, and Stent-Assisted Coil Embolization

Abstract Devices and techniques for the endovascular treatment of intracranial aneurysms have rapidly progressed since their clinical debut nearly three decades ago. However, mastery of basic embolization techniques remains the cornerstone of successful endovascular therapy. Commonly employed techniques include direct, balloon-assisted, and stent-assisted coil embolization. The neuroendovascular field continues to innovate and coil embolization may not remain at the forefront of endovascular aneurysm treatment in the future. The introduction of innovative and promising new devices that do not utilize a coil platform may diminish the future importance of coil embolization techniques leading to a new age in aneurysm embolization where the coil is no longer the dominant device. In this chapter, we will discuss the basics of coil embolization focusing on standard direct, balloon-assisted, and stent-assisted techniques as they remain the workhorse options for aneurysm embolization.

Heparin: The Silver Bullet of Aneurysmal Subarachnoid Hemorrhage?

Various neurological diseases have recently been associated with neuroinflammation and worsening outcomes. Subarachnoid hemorrhage has been shown to generate a potent neuroinflammatory response. Heparin is a potential effective anti-inflammatory agent to prevent initial injury as well as delayed neurological decline. Different mechanisms of action for heparin have been proposed including, but not limited to the binding and neutralization of oxyhemoglobin, decreased transcription and signal transduction of endothelin-1, inhibition of binding to vessel wall selectins and vascular leakage into the subarachnoid space as well as direct binding and neutralization of inflammatory molecules. With a reasonably safe side-effect profile, heparin has shown significant promise in small series in human studies of aneurysmal subarachnoid hemorrhage in decreasing both initial and delayed neurological injury. Further studies are needed to validate various neuroprotective features of heparin in subarachnoid hemorrhage as well as other disease states.

Intra-Arterial Thrombolysis for Acute Central Retinal Artery Occlusion: A Systematic Review and Meta-Analysis

Background and purpose Acute central retinal artery occlusion (CRAO) is a serious ophthalmologic emergency that may result in monocular blindness. To date, studies evaluating intra-arterial thrombolysis (IAT) have not shown a definitive clinical benefit. We have conducted a systematic review with a meta-analysis to effectively evaluate this treatment option. Methods A systematic literature search was focused on studies containing five or more patients undergoing IAT that included a control group treated with standard therapy. Pooled meta-analysis was performed. Results Five retrospective controlled studies and one randomized clinical trial were identified satisfying all inclusion criteria resulting in the analysis of 236 patients treated with IAT and 255 patients treated with ST. A pooled fixed effects analysis resulted in an estimated odds ratio of 2.52, 95% CI (1.69, 3.77) (P < 0.0001) favoring IAT. Conclusion IAT is a promising therapeutic option for CRAO with great potential. Further randomized trials are needed to establish a significant benefit and ensure the safety of the intervention.

MRI SPACE sequence confirmation of occluded MCA M2 dissection stump masquerading as a ruptured MCA aneurysm

Intracranial vascular pathologies often have overlapping clinical presentations. Dissected vessel occlusions and bifurcation aneurysms can appear similar on pretherapeutic imaging. The medical management of these two entities is drastically different. The patient is a 51-year-old man who presented with severe, sudden-onset headache. Initial presentation was consistent with a ruptured middle cerebral artery (MCA) aneurysm and surgical clipping was recommended. However, further review of radiographic findings could not definitively differentiate an aneurysmal origin of the symptoms as opposed to intracranial dissection followed by occlusion of the M2 branch of the MCA. MRI sampling perfection with application optimised contrasts using different flip angle evolution (SPACE) was performed and showed thin flow signalling distal to the dissected vessel stump confirming the diagnosis. Accurate diagnosis is a crucial step in directing treatment for intracranial vascular lesions. MRI SPACE is a simple tool in the diagnostic armamentarium to adequately direct treatment and avoid the potential for unnecessary interventions.

Neuroprotective Strategies in Hemorrhagic Stroke

Hemorrhagic stroke is a devastating disease that represents 10–15% of all strokes in the United States, with high rates of morbidity and mortality. Primary injury to the brain is caused by disruption of the neuronal network, while secondary injury correlates with neuroinflammation, cellular lysis, and perihematomal edema. An approach targeting primary injury involves the evacuation of the intraparenchymal hematoma, which has shown mixed results depending on the invasiveness of the approach. Various neuroprotective strategies have been employed to prevent neuronal damage. Both intraparenchymal and subarachnoid hemorrhages are associated with significant neuroinflammation. Anti-inflammatory pharmacological interventions, such as heparin and glyburide, show significant promise in decreasing the extent of the delayed neurological damage. Other strategies have focused on targeting mitochondria and the final steps of neuronal apoptosis with minocycline, which has showed significant promise in all stroke types. Hemorrhagic stroke remains a devastating disease, and more neuroprotective strategies are needed to maximize the available therapeutic interventions and their effectiveness.