Racial differences in P2Y12 inhibitor responsiveness in patients undergoing neuro-endovascular procedures: A cohort from the Middle East.

BACKGROUND: Data on P2Y12 inhibitors responsiveness from the middle east is scarce. We sought to investigate patient responsiveness to P2Y12 inhibitors within a cohort of major races that characterize the UAE population. The secondary objective was to assess risk factors for hyper and hypo-responsiveness in this population. METHODS: We conducted a cross-sectional study on adults who received either clopidogrel or ticagrelor treatments and had platelet responsiveness testing before undergoing neuro-endovascular interventions at our quaternary care hospital between March 2015 and April 2019. RESULTS: During the study period, 249 subjects met the inclusion criteria. Overall, 17.3 % were hyper-responsive and 25.7 % were hypo-responsive to P2Y12 inhibitors. When comparing between the P2Y12 inhibitors, rates of hyper-responsiveness were significantly higher to ticagrelor when compared to clopidogrel (11 versus 6 %, p = 0.02 respectively). Contrarily, hypo-responsiveness rates were significantly higher in clopidogrel treated patients compared to their ticagrelor treated counterparts (23 versus 2 %, p < .001 respectively). Patients of Middle-Eastern origin showed a significantly higher rate of hypo-responsiveness to both clopidogrel and ticagrelor when compared to other races (41.1 % and 26.7 %, P < 0.001 respectively). Asians showed the highest rates of hyper-responsiveness for both agents. Multivariate logistic regression analysis showed that proton pump inhibitors and statin combination, (OR: 6.39, 95 %CI [1.60, 25.392]), and Middle East vs. Indian subcontinent patients (OR: 4.67, 95 %CI [1.79-12.14]) were independent predictors of hypo-responsiveness to both P2Y12 inhibitors. CONCLUSION: This study demonstrated a high rate of hypo-responsiveness to P2Y12 inhibitors in a UAE cohort of patients undergoing neuro-endovascular procedures. In addition, therapeutic responsiveness to P2Y12 inhibitors varied markedly based on the racial background. Future larger studies are needed to evaluate genetic variations that may contribute to this rate of hypo-responsiveness in our population.

Cerebrovascular Fibromuscular Dysplasia - A Practical Review.

Fibromuscular dysplasia (FMD) is a rare idiopathic, segmental, noninflammatory and nonatherosclerotic arteriopathy of medium-sized arteries. It is classically considered to be a disease of young and middle adulthood, with females more commonly affected than males. FMD is a systemic disease. Although historically considered to be rare, cerebrovascular FMD (C-FMD) has now been recognized to be as common as the renovascular counterpart. Extracranial carotid and vertebral arteries are the most commonly involved vascular territories in C-FMD with the clinical presentation determined by vessels affected. Common symptoms include headaches and pulsatile tinnitus, with transient ischemic attacks, ischemic stroke and subarachnoid or intracerebral hemorrhage constituting the more severe clinical manifestations. Cervical artery dissection involving carotids more often than vertebral arteries and intracranial aneurysms account for the cerebrovascular pathologies detected in C-FMD. Our understanding regarding C-FMD has been augmented in the recent past on account of dedicated C-FMD data from North American, European and other international FMD cohorts. In this review article, we provide an updated and comprehensive overview on epidemiology, clinical presentation, etiology, diagnosis and management of C-FMD.

Primary Sjögren's Syndrome Presenting as Recurrent Ischemic Strokes.

Primary Sjogren's Syndrome (PSS) is an autoimmune exocrinopathy, with protean manifestations affecting multiple organ systems. Neurological manifestations are documented in about 20% of PSS cohorts in literature, with peripheral manifestations being commoner. Central nervous system manifestations of PSS (CNS-SS) encompass ischemic strokes, demyelinating lesions, aseptic meningitis, encephalitis, cerebellar ataxia, cognitive impairment and movement disorders. Ischemic stroke as presenting manifestation of PSS is extremely rare. We hereby describe a 50-year-old male, who presented for evaluation of 2 episodes of discrete focal neurological deficits over a duration of 6 weeks, with neuro-imaging findings revealing evidence of acute-subacute bihemispheric infarcts. Further evaluation revealed evidence of strongly positive anti phospholipid antibodies (aPL), indirect immunofluorescence antinuclear antibody (IIF-ANA), anti Sjögren's syndrome-A (SS-A/Ro) and anti-Ribonuclear protein (RNP) antibodies, with histopathological evidence of periductal and periacinar lymphocytic infiltration as well as acinar atrophy and interstitial fibrosis of minor salivary glands on lip biopsy, consistent with a diagnosis of Sjögren's syndrome, constituting a diagnosis of Antiphospholipid syndrome (APS) associated with PSS.

Endovascular Embolization of Intracranial Infectious Aneurysms in Patients Undergoing Open Heart Surgery Using n-Butyl Cyanoacrylate.

INTRODUCTION: Mycotic aneurysms are a serious complication of infective endocarditis with increased risk of intracranial hemorrhage. Patients undergoing open heart surgery for valve repair or replacement are exposed to anticoagulants, increasing the risk of aneurysm bleeding. These patients may require endovascular or surgical aneurysm treatment prior to heart surgery, but data on this approach are scarce. METHODS: Retrospective review of consecutive patients with infectious endocarditis and mycotic aneurysms treated endovascularly with Trufill n-butyl cyanoacrylate (n-BCA) at the Cleveland Clinic between January 2013 and December 2015. RESULTS: Nine patients underwent endovascular treatment of mycotic aneurysms with n-BCA (mean age of 39 years). On imaging, 4 patients had intracerebral hemorrhage, 2 had multiple embolic infarcts, and the rest had no imaging findings. Twelve mycotic aneurysms were detected (3 patients with 2 aneurysms). Seven aneurysms were in the M4 middle cerebral artery segment, 4 in the posterior cerebral artery distribution, and 1 in the callosomarginal branch. n-BCA was diluted in ethiodized oil (1:1 to 1:2). Embolization was achieved in a single rapid injection with immediate microcatheter removal. Complete aneurysm exclusion was achieved in all cases without complications. All patients underwent open heart surgery and endovascular embolization within a short interval, 2 with both procedures on the same day. There were no new hemorrhages after aneurysm embolization. CONCLUSIONS: Endovascular embolization of infectious intracranial aneurysms with liquid embolics can be performed successfully in critically ill patients requiring immediate open heart surgery and anticoagulation. Early embolization prior to and within a short interval from open heart surgery is feasible.

ASPECTS discrepancies between CT and MR imaging: analysis and implications for triage protocols in acute ischemic stroke.

BACKGROUND: Optimal imaging triage for intervention for large vessel occlusions remains unclear. MR-based imaging provides ischemic core volumes at the cost of increased imaging time. CT Alberta Stroke Program Early CT Score (ASPECTS) estimates are faster, but may be less sensitive. OBJECTIVE: To assesses the rate at which MRI changed management in comparison with CT imaging alone. METHODS: Retrospective analysis of patients with acute ischemic stroke undergoing imaging triage for endovascular therapy was performed between 2008 and 2013. Univariate and multivariate analyses were performed. Multivariate logistic regression was used to evaluate the effect of time on disagreement in MRI and CT ASPECTS scores. RESULTS: A total of 241 patients underwent both diffusion-weighted imaging (DWI) and CT. Six patients with DWI ASPECTS ≥6 and CT ASPECTS <6 were omitted, leaving 235 patients. For 47 patients, disagreement between the two modalities resulted in different treatment recommendations. The estimated probability of disagreement was 20.0% (95% CI 15.4% to 25.6%). In a multivariate logistic regression, CT ASPECTS >7 (p=0.004) and admission National Institutes of Health Stroke Scale (NIHSS) score <16 (p=0.008) were simultaneously significant predictors of agreement in ASPECTS. The time between modalities was a marginally significant predictor (p=0.080). CONCLUSIONS: The study suggests that patients with NIHSS scores at admission of <16 and patients with CT ASPECTS >7 have a higher likelihood of agreement between CT and DWI based on an ASPECTS cut-off value of 6. Additional MRI for triage in patients with NIHSS at admission of >16, and ASPECTS of 6 or 7 may be more likely to change management. Unsurprisingly, patients with low CT ASPECTS had good correlation with MRI ASPECTS.

Predictors for venous sinus stent retreatment in patients with idiopathic intracranial hypertension.

BACKGROUND: Venous sinus stenting for dural sinus stenoses is an emerging alternative to cerebrospinal fluid diversion in cases of medically refractory idiopathic intracranial hypertension. Juxta-stent 're-stenoses' have been reported and managed alternatively with ventricular shunting or stent revision. Identification of factors that might predispose patients to recurrent narrowing may help to select or exclude patients with idiopathic intracranial hypertension for venous sinus stenting. METHODS: We retrospectively reviewed a prospectively maintained database spanning December 2011 to May 2015 of all patients with idiopathic intracranial hypertension who were screened for possible venous sinus stenting, including only patients who received a stent, noting symptomatic improvements, changes in opening lumbar puncture pressure, demographic characteristics, and any subsequent intervention after stent placement. Fisher's exact test and logistic regression were used to test each of seven potential predictors for retreatment. RESULTS: There were eight revisions in 31 patients (25.8%). Among Caucasians, 8.0% required a revision compared with 100% of African-Americans (p<0.001). The c-index for race was 0.857. Body mass index (BMI) was also a significant predictor of revision (p=0.031): among class III obese patients the revision rate was 46.2% compared with 16.7% among class I and II obese patients and 0% among overweight to normal weight patients. CONCLUSIONS: BMI was a significant predictor of revision, suggesting that higher BMI may have a higher risk of revision. The small number of African-Americans in the study makes interpretation of the practical significance of the revision rate in these patients uncertain. None of the other studied factors was statistically significant.

Timeline of blood pressure changes after intra-arterial therapy for acute ischemic stroke based on recanalization status.

BACKGROUND: There is sparse literature on the natural history of blood pressure (BP) after intra-arterial therapy (IAT) for acute ischemic stroke (AIS). METHODS: A retrospective analysis was performed of patients with AIS who underwent IAT without endotracheal intubation for internal carotid artery terminus (ICA-T) or M1 middle cerebral artery occlusion from January 2008 to February 2012. Systolic BP (SBP) values at the beginning (First) and end (End) of IAT and for 36 h after the procedure were collected. Successful recanalization was defined as Thrombolysis In Cerebral Infarction (TICI) 2b-3. RESULTS: Sixty-two patients (14 (22.5%) ICA-T, 46 (74.2%) M1, 2 (3.2%) ICA-T+M1) met the study criteria and 37 (59.7%) achieved successful recanalization. The First and End SBP values were similar in the successful (Group R) and unsuccessful (Group NR) recanalization groups. Taking the whole cohort, End SBP was significantly lower than First SBP, but this decline was significant only in Group R. Subsequently, absolute SBP values in Group R were not significantly different from Group NR. However, when comparing the hourly decline of SBP with First SBP, Group R demonstrated a greater fall than Group NR and the decline was significantly different from hours 8 to 12 post-procedure. The SBP in Group NR then decreased further, and its difference from baseline was similar to Group R from hour 14 onwards. Mean SBP and SBP variability over 36 h were similar between the two groups. CONCLUSIONS: SBP falls significantly in patients with AIS with large vessel occlusion who recanalize with IAT. While SBP in non-recanalized patients also drops from baseline, it occurs to a lesser degree and stays higher only for a short period of time before falling to similar levels as in recanalized patients.

Thoracolumbar Arteriovenous Malformations Presenting with Intracranial Subarachnoid Hemorrhage: Case Series and Review of Literature.

OBJECTIVE: Cryptogenic intracranial subarachnoid hemorrhage accounts for approximately 15% of all subarachnoid hemorrhage cases. Diagnostic workup after negative cerebral digital subtraction angiogram typically includes magnetic resonance imaging of the brain and cervical spine for arteriovenous malformations, tumors, and fistulae. Only a few cases of thoracolumbar spinal vascular malformations have been associated with intracranial subarachnoid hemorrhage. METHODS: Case series and review of the literature. RESULTS: We found 3 patients at our institution who had nontraumatic, nonaneurysmal intracranial subarachnoid hemorrhage with isolated spinal vascular malformation in the thoracolumbar region. Including our 3 cases, we found a total of 15 similar cases in the literature. Most of the patients were younger, most having concurrent spinal cord symptoms of radiculopathy (27%), myelopathy (20%), or bladder bowel involvement (20%). Most of the spinal vascular malformations were intramedullary or conus medullaris type. Locations of intracranial subarachnoid hemorrhage were mostly isolated to the perimesencephalic area and posterior fossa. CONCLUSIONS: In younger populations presenting with nonaneurysmal intracranial subarachnoid hemorrhage and symptoms related to the spinal cord, evaluation for thoracolumbar spinal vascular malformations must be included in the initial workup.

Brain Imaging Using Mobile CT: Current Status and Future Prospects.

Computed tomography (CT) is an invaluable tool in the diagnosis of many clinical conditions. Several advancements in biomedical engineering have achieved increase in speed, improvements in low-contrast detectability and image quality, and lower radiation. Portable or mobile CT constituted one such important advancement. It is especially useful in evaluating critically ill, intensive care unit patients by scanning them at bedside. A paradigm shift in utilization of mobile CT was its installation in ambulances for the management of acute stroke. Given the time sensitive nature of acute ischemic stroke, Mobile stroke units (MSU) were developed in Germany consisting of an ambulance equipped with a CT scanner, point of care laboratory system, along with teleradiological support. In a radical reconfiguration of stroke care, the MSU would bring the CT scanner to the stroke patient, without waiting for the patient at the emergency room. Two separate MSU projects in Saarland and Berlin demonstrated the safety and feasibility of this concept for prehospital stroke care, showing increased rate of intravenous thrombolysis and significant reduction in time to treatment compared to conventional care. MSU also improved the triage of patients to appropriate and specialized hospitals. Although multiple issues remain yet unanswered with the MSU concept including clinical outcome and cost-effectiveness, the MSU venture is visionary and enables delivery of life-saving and enhancing treatment for ischemic and hemorrhagic stroke. In this review, we discuss the development of mobile CT and its applications, with specific focus on its use in MSUs along with our institution's MSU experience.

Emergent mechanical thrombectomy for acute stroke using the Mindframe Capture LP system: initial single-center experience.

BACKGROUND: Mechanical thrombectomy using stentrievers is the standard of care for emergent large vessel occlusion stroke. Data on the use of stentrievers in smaller caliber vessels are sparse. OBJECTIVE: To present our initial experience with the Mindframe Capture LP device, which was designed for mechanical thrombectomy in small cerebral arteries. METHODS: A retrospective chart review was conducted of patients who underwent Mindframe device assisted emergent thrombectomy. Clinical, imaging, procedural and early follow-up data were obtained. RESULTS: Nine patients met inclusion criteria (5 men, median age 62 years). Median National Institute of Health Stroke Scale (NIHSS) score was 18 (IQR 9-22), and 6 patients received intravenous tissue plasminogen activator. Six patients had M2 segment occlusions, and 2 patients had distal M1 segment occlusions of the middle cerebral artery. One had distal basilar artery occlusion. Median vessel diameter at the thrombus was 1.7 mm (IQR 1.5-2.5). In all 9 patients the Mindframe device was used together with manual aspiration, with median groin puncture to recanalization time of 35 min (IQR 27-54), and median procedural time of 67 min (IQR 51-91). Final Thrombolysis in Cerebral Infarction score was 3 and 2b in 4 patients each (89% total), and 2a in 1 patient. No patient had any postprocedural complications or symptomatic intracerebral hemorrhage. Median postprocedure and discharge NIHSS were 4 and 1, respectively. CONCLUSIONS: Our data suggest that the Mindframe device is safe and effective for rapid treatment of acute strokes involving small caliber intracranial vessels. Further study in a larger cohort is warranted.

Reduction in Syrinx Size and Severity After Venous Sinus Stenting in a Patient With Pseudotumor Cerebri and Chiari Malformation: Technical Case Report.

BACKGROUND AND IMPORTANCE: Pseudotumor cerebri and Chiari I malformation are found to coexist in a subset of patients. Surgical cranial decompression has been the mainstay of Chiari malformation management, whereas venous sinus stenting has emerged as an effective treatment modality for pseudotumor cerebri. Gaps in our current understanding of cerebrospinal fluid (CSF) circulation and the pathophysiology behind CSF-related disorders present difficulties in the simultaneous management of these conditions. A case is presented of the successful management of both conditions with venous sinus stenting, with sustained improvement in symptoms and structural abnormalities of the Chiari malformation and associated syrinxes. CLINICAL PRESENTATION: An obese woman in her 20s with a history of occipital headaches who presented with progressively worsening intermittent visual obscurations was diagnosed with pseudotumor cerebri, Chiari I malformation, and associated spinal syrinxes. Magnetic resonance venography demonstrated right transverse sinus narrowing with an elevated pressure gradient. Successful endovascular intervention with venous sinus stenting achieved normalization of the venous sinus pressure gradient and symptomatic improvement. After stenting, the cervical syrinx was observed to have decreased in size, with a decrease in the extent of cerebellar tonsillar herniation and an increase in CSF signal around the cerebellar tonsils. CONCLUSION: Venous sinus stenting for treatment of concomitant pseudotumor cerebri and Chiari I malformation can be effective in patients demonstrating transverse sinus stenosis.

CNS vasculitis.

Central nervous system vasculitis (CNSV) is a complex disease that poses considerable diagnostic and therapeutic challenges. It is divided into primary angiitis of the CNS (PACNS), or secondary angiitis of the CNS when associated with systemic conditions. Clinical presentation can be extremely variable and there is no classic presentation. In addition, there is no single diagnostic test and the sensitivity/specificity of all currently available tests is suboptimal. As such, an exhaustive approach with thorough historical data, physical examination, and corroborating investigations should be performed to exclude or confirm a diagnosis of CNSV. Infectious, neoplastic, and autoimmune conditions should be carefully evaluated. Knowledge of CNSV mimics is crucial given the therapeutic and prognostic implications. Reversible cerebral vasoconstriction syndrome is now recognized as the most common mimicker of PACNS. Much progress has been made in the understanding of PACNS histopathology, and specific clinical subsets and their response to treatment. Contrary to historical reports, recent PACNS cohorts achieved favorable clinical outcomes when early diagnosis and prompt treatment was initiated. Successful treatment with newer drugs has also been reported in PACNS cases. Newer imaging modalities hold promise for distinguishing inflammatory from noninflammatory vascular lesions. In this review, the authors provide a broad overview with updates on the types of adult CNSV along with its clinical assessment, diagnosis, and treatment.

Last resort: case of clot translocation in intra-arterial stroke therapy.

A patient was taken for emergent intra-arterial stroke therapy for an acute left middle cerebral artery stroke syndrome, with CT angiography showing a left internal carotid artery (ICA) occlusion. Through a 6 F Neuron MAX sheath, a 5 Max ACE Penumbra aspiration catheter was advanced to the thrombus and direct suction was performed through the ACE catheter and Neuron MAX sheath. Upon pull back, the thrombus became wedged in the Neuron MAX sheath and despite several attempts to aspirate the thrombus, no clot could be obtained. The Neuron MAX sheath was withdrawn to the left common carotid artery, and gently advanced to the origin of the external carotid artery (ECA). A glide wire was advanced and the thrombus dislodged into the ECA. Another pass with the 5 Max ACE was used to remove a remaining thrombus in the left ICA terminus, resulting in Thrombolysis in Cerebral Infarction (TICI) 3 flow. With improved devices for embolectomy, large and rigid emboli that exceed the inner diameter of large guide sheaths and balloon guide catheters can become lodged, and cannot be withdrawn through a catheter. While uncommon, strategies to overcome this are important to keep in mind during acute stroke intervention.

Initial experience with the coaxial dual-lumen Scepter C balloon catheter for endovascular management of cerebral vasospasm from subarachnoid hemorrhage.

BACKGROUND: Post-hemorrhagic cerebral vasospasm accounts for significant morbidity and mortality in patients with subarachnoid hemorrhage (SAH). Intra-arterial therapies including vasodilator administration and/or balloon angioplasty are used when medical management fails. The Scepter C is a newer dual coaxial lumen temporary occlusion balloon catheter used for the treatment of post-hemorrhagic cerebral vasospasm. OBJECTIVE: To report our early experience with the use of Scepter C for the treatment of post-hemorrhagic cerebral vasospasm. METHODS: We reviewed cases from two institutions where the Scepter C balloon catheter was used for the treatment of cerebral vasospasm related to SAH. RESULTS: Seven patients were identified who underwent endovascular treatment with the Scepter C balloon catheter for treatment of SAH-related cerebral vasospasm. All patients had cerebral vasospasm that was refractory to medical management and it was technically feasible to use the catheter for this indication. Compared with larger double-lumen catheters, the Scepter C catheter was more trackable given the presence of a more steerable microwire. There were no complications or large vessel vasospasm recurrence after the procedure requiring repeat intra-arterial therapy. CONCLUSIONS: Endovascular treatment for post-hemorrhagic cerebral vasospasm is used when medical management fails or because of complications of medical therapies. With continuing advancements in the development of endovascular devices and techniques, more options are available for the management of cerebral vasospasm. Our initial experience with the dual coaxial lumen Scepter C occlusion balloon catheter demonstrates its feasibility in the treatment of cerebral vasospasm.

Catastrophic reversible cerebral vasoconstriction syndrome associated with serotonin syndrome.

OBJECTIVES: To report fulminant cases of reversible cerebral vasoconstriction syndrome (RCVS) in the setting of serotonin syndrome. BACKGROUND: RCVS is characterized by acute onset of severe headaches, with or without neurologic deficit, with evidence of reversible cerebral vasoconstriction. It is often benign, and prognosis is generally considered favorable. In the largest prospective study on RCVS, only 4% of patients were disabled from strokes and there were no fatalities. METHODS: We report a case series. RESULTS: We report 2 women with history of depression on selective serotonin re-uptake inhibitors who presented with thunderclap headache and dizziness, respectively. Through the course of hospitalization, both patients developed rigidity, diaphoresis, fever, tachycardia with labile blood pressures and clonus on examination. Since there was a recent addition/increase in a known serotonergic agent, they met criteria for serotonin syndrome. Cerebrovascular imaging in both patients revealed severe multi-focal vessel narrowing. The first patient developed large bi-hemispheric ischemic infarcts and increased intra-cranial pressure that was refractory to management, and she eventually expired. The second patient developed bilateral parieto-occipital strokes and decerebrate posturing. Her course slowly stabilized, and she was eventually discharged with residual left-sided hemiparesis. Repeat cerebrovascular imaging 1 month later showed normal vessels. In both patients, intra-arterial nicardipine infusion improved angiographic appearance of stenoses, consistent with RCVS. CONCLUSIONS: Both cases satisfied the Sternbach criteria for serotonin syndrome. Fatality in case 1 prevents demonstration of reversal of cerebral vasoconstriction, but improvement of arterial diameters with intra-arterial calcium channel blockers in both cases suggests that both had RCVS. Serotonergic agents are known triggers of RCVS, but the concurrent presence of serotonin syndrome likely precipitated the malignant course in our patients. Severe clinical and angiographic manifestations should be considered as part of the spectrum of RCVS.

Tumefactive perivascular spaces mimicking cerebral edema in a patient with diabetic hyperglycemic hyperosmolar syndrome: a case report.

INTRODUCTION: Acute cerebral edema is a significant cause of death in patients treated for diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome. CASE PRESENTATION: We present the case of a 44-year-old African American woman admitted with acute severe headache and diagnosed with diabetic hyperglycemic hyperosmolar syndrome. Computed tomography of the head showed diffuse leukoencephalopathy, but sparing of the cortex. We were concerned for acute cerebral edema secondary to hyperglycemic hyperosmolar syndrome. Magnetic resonance imaging of the brain showed numerous collections of cystic spaces in the white matter of both hemispheres representing tumefactive perivascular spaces. Her headache improved with correction of the hyperglycemic hyperosmolar state. CONCLUSION: Although the clinical presentation and head computed tomography were concerning for cerebral edema, the distinctive features on brain magnetic resonance imaging helped to clarify the diagnosis and differentiate it from other processes.