Brian-Fred Fitzsimmons

Recommendations on Angiographic Revascularization Grading Standards for Acute Ischemic Stroke A Consensus Statement

See related article, p 2509 Intra-arterial therapy (IAT) for acute ischemic stroke (AIS) has dramatically evolved during the past decade to include aspiration and stent-retriever devices. Recent randomized controlled trials have demonstrated the superior revascularization efficacy of stent-retrievers compared with the first-generation Merci device.1,2 Additionally, the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) 2, the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE), and the Interventional Management of Stroke (IMS) III trials have confirmed the importance of early revascularization for achieving better clinical outcome.3–5 Despite these data, the current heterogeneity in cerebral angiographic revascularization grading (CARG) poses a major obstacle to further advances in stroke therapy. To date, several CARG scales have been used to measure the success of IAT.6–14 Even when the same scale is used in different studies, it is applied using varying operational criteria, which further confounds the interpretation of this key metric.10 The lack of a uniform grading approach limits comparison of revascularization rates across clinical trials and hinders the translation of promising, early phase angiographic results into proven, clinically effective treatments.6–14 For these reasons, it is critical that CARG scales be standardized and end points for successful revascularization be refined.6 This will lead to a greater understanding of the aspects of revascularization that are strongly predictive of clinical response. The optimal grading scale must demonstrate (1) a strong correlation with clinical outcome, (2) simplicity and feasibility of scale interpretation while ensuring characterization of relevant angiographic findings, and (3) high inter-rater reproducibility. To address these issues, a multidisciplinary panel of neurointerventionalists, neuroradiologists, and stroke neurologists with extensive experience in neuroimaging and IAT, convened at the “Consensus Meeting on Revascularization Grading Following Endovascular Therapy” with the goal …

Cardiac Troponin Elevation, Cardiovascular Morbidity, and Outcome After Subarachnoid Hemorrhage

Background— Cardiac troponin I (cTI) release occurs frequently after subarachnoid hemorrhage (SAH) and has been associated with a neurogenic form of myocardial injury. The prognostic significance and clinical impact of these elevations remain poorly defined. Methods and Results— We studied 253 SAH patients who underwent serial cTI measurements for clinical or ECG signs of potential cardiac injury. These patients were drawn from an inception cohort of 441 subjects enrolled in the Columbia University SAH Outcomes Project between November 1998 and August 2002. Peak cTI levels were divided into quartiles or classified as undetectable. Adverse in-hospital events were prospectively recorded, and outcome at 3 months was assessed with the modified Rankin Scale. Admission predictors of cTI elevation included poor clinical grade, intraventricular hemorrhage, loss of consciousness at ictus, global cerebral edema, and a composite score of physiological derangement (all P≤0.01). Peak cTI level was associated with an increased risk of echocardiographic left ventricular dysfunction (odds ratio [OR], 1.3 per quintile; 95% CI, 1.0 to 1.7; P=0.03), pulmonary edema (OR, 2.1 per quintile; 95% CI, 1.6 to 2.7; P<0.001), hypotension requiring pressors (OR, 1.9 per quintile; 95% CI, 1.5 to 2.3; P<0.001), and delayed cerebral ischemia from vasospasm (OR, 1.3 per quintile; 95% CI, 1.07 to 1.7; P=0.01). Peak cTI levels were predictive of death or severe disability at discharge after controlling for age, clinical grade, and aneurysm size (adjusted OR, 1.4 per quintile; 95% CI, 1.1 to 1.9; P=0.02), but this association was no longer significant at 3 months. Conclusions— cTI elevation after SAH is associated with an increased risk of cardiopulmonary complications, delayed cerebral ischemia, and death or poor functional outcome at discharge.

Phenytoin Exposure Is Associated With Functional and Cognitive Disability After Subarachnoid Hemorrhage

Background and Purpose— Phenytoin (PHT) is routinely used for seizure prophylaxis after subarachnoid hemorrhage (SAH), but may adversely affect neurologic and cognitive recovery. Methods— We studied 527 SAH patients and calculated a “PHT burden” for each by multiplying the average serum level of PHT by the time in days between the first and last measurements, up to a maximum of 14 days from ictus. Functional outcome at 14 days and 3 months was measured with the modified Rankin scale, with poor functional outcome defined as dependence or worse (modified Rankin Scale ≥4). We assessed cognitive outcomes at 14 days and 3 months with the telephone interview for cognitive status. Results— PHT burden was associated with poor functional outcome at 14 days (OR, 1.5 per quartile; 95% CI, 1.3 to 1.8; P<0.001), although not at 3 months (P=0.09); the effect remained (OR, 1.6 per quartile; 95% CI, 1.2 to 2.1; P<0.001) after correction for admission Glasgow Coma Scale, fever, stroke, age, National Institutes of Health Stroke Scale ≥10, hydrocephalus, clinical vasospasm, and aneurysm rebleeding. Seizure in hospital (OR, 4.1; 95% CI, 1.5 to 11.1; P=0.002) was associated with functional disability in a univariate model only. Higher quartiles of PHT burden were associated with worse telephone interview for cognitive status scores at hospital discharge (P<0.001) and at 3 months (P=0.003). Conclusions— Among patients treated with PHT, burden of exposure to PHT predicts poor neurologic and cognitive outcome after SAH.

Clinical trial of a novel surface cooling system for fever control in neurocritical care patients

Objective:To compare the efficacy of a novel water-circulating surface cooling system with conventional measures for treating fever in neuro-intensive care unit patients. Design:Prospective, unblinded, randomized controlled trial. Setting:Neurologic intensive care unit in an urban teaching hospital. Patients:Forty-seven patients, the majority of whom were mechanically ventilated and sedated, with fever ≥38.3°C for >2 consecutive hours after receiving 650 mg of acetaminophen. Interventions:Subjects were randomly assigned to 24 hrs of treatment with a conventional water-circulating cooling blanket placed over the patient (Cincinnati SubZero, Cincinnati OH) or the Arctic Sun Temperature Management System (Medivance, Louisville CO), which employs hydrogel-coated water-circulating energy transfer pads applied directly to the trunk and thighs. Measurements and Main Results:Diagnoses included subarachnoid hemorrhage (60%), cerebral infarction (23%), intracerebral hemorrhage (11%), and traumatic brain injury (4%). The groups were matched in terms of baseline variables, although mean temperature was slightly higher at baseline in the Arctic Sun group (38.8 vs. 38.3°C, p = .046). Compared with patients treated with the SubZero blanket (n = 24), Arctic Sun-treated patients (n = 23) experienced a 75% reduction in fever burden (median 4.1 vs. 16.1 C°-hrs, p = .001). Arctic Sun-treated patients also spent less percent time febrile (T ≥38.3°C, 8% vs. 42%, p < .001), spent more percent time normothermic (T ≤37.2°C, 59% vs. 3%, p < .001), and attained normothermia faster than the SubZero group median (2.4 vs. 8.9 hrs, p = .008). Shivering occurred more frequently in the Arctic Sun group (39% vs. 8%, p = .013). Conclusion:The Arctic Sun Temperature Management System is superior to conventional cooling-blanket therapy for controlling fever in critically ill neurologic patients.

Interventional Acute Ischemic Stroke Therapy With Intracranial Self-Expanding Stent

Background and Purpose— Rapid and safe recanalization of occluded intracranial arteries in acute ischemic stroke (AIS) is challenging. Newly available self-expanding intracranial atherosclerotic stents (SEIS), which can be deployed rapidly and safely, make acute stenting an option for treating AIS. We present the feasibility of this technique. Methods— A retrospective analysis evaluated procedural protocols and clinical response to treatment in patients with AIS treated with SEIS. Descriptive statistics are presented with initial and follow-up National Institutes of Health Stroke Scale and modified Rankin Score. Results— Nine patients with AIS underwent acute SEIS placement. There was successful deployment of the Neuroform (n=4) and Wingspan (n=4/5) stents in the M1/M2 (n=5) and M3 (n=1) middle cerebral artery segments, intracranial internal carotid artery (one of 2), and intracranial vertebrobasilar junction (one). Mean time of SEIS deployment from AIS onset was 5.1 hours. Complete (Thrombolysis in Cerebral Ischemia/Thrombolysis in Myocardial Ischemia 3) and partial/complete (Thrombolysis in Cerebral Ischemia/Thrombolysis in Myocardial Ischemia 2 or 3) recanalization occurred in 67% and 89%, respectively. One intracranial hemorrhage (11%) and one acute in-stent thrombosis (successfully treated with abciximab and balloon angioplasty) occurred. Stroke-related mortality occurred in 3 of 9 (33%) patients and survivors had modified Rankin Score ≤2. Follow-up angiography (mean, 8 months; range, 2 to 14 months) in 4 of 9 patients showed no stent restenosis. Conclusions— This preliminary experience with SEIS in refractory AIS demonstrated the technical feasibility and high rate of recanalization with acute stenting. Long-term safety and strategies to limit in-stent thrombosis and optimize periprocedural management are crucial before initiating future randomized efficacy studies with SEIS in AIS refractory to standard therapy.

Predictors of functional disability and mortality after status epilepticus

The authors identified predictors of functional disability and mortality after status epilepticus in a multivariate analysis of 83 episodes in 74 patients. Twenty-one percent (14/85) of episodes were fatal. Increased age (OR = 1.1; 95% CI, 1.0 to 1.1) and acute symptomatic seizures (OR = 6.0; 95% CI, 1.2 to 30.3) were predictors of mortality. Functional outcome at discharge deteriorated in 23% (16/69) of nonfatal episodes. Increased length of hospitalization (OR = 1.04; 95% CI, 1.0 to 1.1) and acute symptomatic seizures (OR = 3.9; 95% CI, 1.0 to 14.7) were predictors of functional disability.

Effect of prior statin use on functional outcome and delayed vasospasm after acute aneurysmal subarachnoid hemorrhage: a matched controlled cohort study.

OBJECTIVE:Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), which exhibit beneficial cerebrovascular effects by modulating inflammation and nitric oxide production, have not been evaluated in acute aneurysmal subarachnoid hemorrhage (SAH) patients. The effect of prior statin use on 14-day functional outcome and on prevention of vasospasm-induced delayed cerebral ischemia (DCI) or stroke during hospitalization was analyzed. METHODS:We conducted a 1:2 matched (age, admission Hunt and Hess grade, vascular disease/risk history) cohort study of 20 SAH patients on statins and 40 SAH controls. The primary outcome was functional outcome at 14 days (Modified Lawton Physical Self-Maintenance Scale and Barthel Index scale scores). Secondary outcomes were 14-day mortality, Modified Rankin Scale score, DCI, DCI supported by angiography/transcranial Doppler [TCD], cerebral infarctions of any type, and TCD highest mean velocity elevation. RESULTS:Statin users demonstrated a significant protective effect on 14-day Barthel Index scale and Modified Lawton Physical Self-Maintenance Scale scores (77 ± 10 versus 39 ± 8, P = 0.003; 12 ± 7 versus 19 ± 9, P = 0.03, respectively). Moreover, statin users demonstrated a significantly lower incidence of DCI and DCI supported by angiography/TCD (10% versus 43%, P = 0.02; 5% versus 35%, P = 0.01, respectively), cerebral infarctions of any type (25% versus 63%, P = 0.01), and baseline-to-final TCD highest mean velocity change of 50 cm/s or greater (18% versus 51%, P = 0.03). CONCLUSION:SAH statin users demonstrated significant improvement in 14-day functional outcome, a significantly lower incidence of DCI and cerebral infarctions of any type, as well as prevention of TCD highest mean velocity elevation. However, we did not find a significant statin impact on mortality or global outcome (Modified Rankin Scale) in this small sample. This study provides clinical evidence for the potential therapeutic benefit of statins after acute SAH.

Effect of a Balloon-Expandable Intracranial Stent vs Medical Therapy on Risk of Stroke in Patients With Symptomatic Intracranial Stenosis: The VISSIT Randomized Clinical Trial

IMPORTANCE Intracranial stenosis is one of the most common etiologies of stroke. To our knowledge, no randomized clinical trials have compared balloon-expandable stent treatment with medical therapy in symptomatic intracranial arterial stenosis. OBJECTIVE To evaluate the efficacy and safety of the balloon-expandable stent plus medical therapy vs medical therapy alone in patients with symptomatic intracranial stenosis (≥70%). DESIGN, SETTING, AND PATIENTS VISSIT (the Vitesse Intracranial Stent Study for Ischemic Stroke Therapy) trial is an international, multicenter, 1:1 randomized, parallel group trial that enrolled patients from 27 sites (January 2009-June 2012) with last follow-up in May 2013. INTERVENTIONS Patients (N = 112) were randomized to receive balloon-expandable stent plus medical therapy (stent group; n = 59) or medical therapy alone (medical group; n = 53). MAIN OUTCOMES AND MEASURES PRIMARY OUTCOME MEASURE a composite of stroke in the same territory within 12 months of randomization or hard transient ischemic attack (TIA) in the same territory day 2 through month 12 postrandomization. A hard TIA was defined as a transient episode of neurological dysfunction caused by focal brain or retinal ischemia lasting at least 10 minutes but resolving within 24 hours. Primary safety measure: a composite of any stroke, death, or intracranial hemorrhage within 30 days of randomization and any hard TIA between days 2 and 30 of randomization. Disability was measured with the modified Rankin Scale and general health status with the EuroQol-5D, both through month 12. RESULTS Enrollment was halted by the sponsor after negative results from another trial prompted an early analysis of outcomes, which suggested futility after 112 patients of a planned sample size of 250 were enrolled. The 30-day primary safety end point occurred in more patients in the stent group (14/58; 24.1% [95% CI, 13.9%-37.2%]) vs the medical group (5/53; 9.4% [95% CI, 3.1%-20.7%]) (P = .05). Intracranial hemorrhage within 30 days occurred in more patients in the stent group (5/58; 8.6% [95% CI, 2.9%-19.0%]) vs none in the medical group (95% CI, 0%-5.5%) (P = .06). The 1-year primary outcome of stroke or hard TIA occurred in more patients in the stent group (21/58; 36.2% [95% CI, 24.0-49.9]) vs the medical group (8/53; 15.1% [95% CI, 6.7-27.6]) (P = .02). Worsening of baseline disability score (modified Rankin Scale) occurred in more patients in the stent group (14/58; 24.1% [95% CI, 13.9%-37.2%]) vs the medical group (6/53; 11.3% [95% CI, 4.3%-23.0%]) (P = .09).The EuroQol-5D showed no difference in any of the 5 dimensions between groups at 12-month follow-up. CONCLUSIONS AND RELEVANCE Among patients with symptomatic intracranial arterial stenosis, the use of a balloon-expandable stent compared with medical therapy resulted in an increased 12-month risk of added stroke or TIA in the same territory, and increased 30-day risk of any stroke or TIA. These findings do not support the use of a balloon-expandable stent for patients with symptomatic intracranial arterial stenosis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00816166.

Monitoring of Cerebral Vasodilatory Capacity With Transcranial Doppler Carbon Dioxide Inhalation in Patients With Severe Carotid Artery Disease

Background and Purpose— Cerebral vasodilatory capacity (CVC) testing with transcranial Doppler has been shown to be useful in the assessment of stroke risk in patients with symptomatic and asymptomatic internal carotid artery (ICA) stenosis and occlusion, but whether hemodynamic status improves, deteriorates, or remains the same over time is uncertain. Methods— Thirty-five patients with ≥80% carotid artery stenosis or complete occlusion underwent CVC testing at baseline and 6 months later. CVC was assessed by measuring the increase in ipsilateral middle cerebral artery mean flow velocity in response to 5% inhaled CO2. Continuous tracings of left and right middle cerebral artery flow velocity, heart rate, respiratory rate, and Pco2 were recorded and then analyzed offline. One-way analysis of variance was used to compare baseline CVC in symptomatic and asymptomatic patients with control subjects. A paired t test was used to compare CVC before and after revascularization. Also, &khgr;2 analysis was used to compare rates of cerebrovascular events in patients with low compared with normal CVC over the 6-month period and in 14 patients whose ICAs were revascularized. Results— Patients with high-grade stenosis or occlusion of the ICA who had ICA disease had an average CVC of 2.4±1.9%/mm Hg Pco2; control subjects averaged 4.2±1.1%/mm Hg Pco2. (P =0.01). In the revascularization group, CVC increased from an average of 1.4±1.7%/mm Hg Pco2 at baseline to an average of 2.8±1.0%/mm Hg Pco2 after revascularization, significantly different from the spontaneous change in the natural history group over 6 months (P =0.003). Over the 6-month follow-up period, in the natural history group and in the treatment group after revascularization, 4 ischemic events occurred, all in patients with abnormal CVCs; abnormal CVC was associated with ischemic events (Fisher’s exact test, P =0.03). Conclusions— In a timeframe pertinent to clinical decision making and clinical trial outcomes, cerebral hemodynamic status may not be constant. A higher ischemic risk may be present in patients with severe carotid artery disease whose CVC is poor at baseline, becomes poor over 6 months, or fails to normalize after revascularization.

Herniation Secondary to Critical Postcraniotomy Cerebrospinal Fluid Hypovolemia

OBJECTIVE:Cerebrospinal fluid hypovolemia resulting in postural headaches is a well-known clinical entity, but severe forms of cerebrospinal fluid hypovolemia with altered mental status and signs of transtentorial herniation (“brain sag”) have rarely been reported. This article describes the clinical features of brain sag after craniotomy in an attempt to increase recognition of this syndrome. METHODS:Between April 2001 and January 2003, 220 consecutive patients with subarachnoid hemorrhage were prospectively enrolled in the Columbia Subarachnoid Hemorrhage Outcomes Project; 137 underwent craniotomy for aneurysm clipping. Among these patients, the diagnosis of brain sag was made when all three of the following criteria were present: clinical signs of transtentorial herniation, head computed tomographic scans revealing effacement of the basal cisterns with an oblong brainstem, and improvement of symptoms after placement of the patient in the Trendelenburg position (–15 to –30 degrees). For each patient, the symptoms, clinical course, and subsequent response to treatment were characterized. In addition, brainstem dimensions were measured on computed tomographic scans taken before, during, and after resolution of brain sag. A “sag ratio” was generated for these time points by dividing the maximum anteroposterior distance by the maximum bipeduncular distance. RESULTS:Eleven (8.0%) of 137 aneurysmal subarachnoid hemorrhage patients treated by craniotomy and an intraoperative spinal drain met the criteria for brain sag. Signs of transtentorial herniation developed most commonly between 2 and 4 days postoperatively. Pupillary asymmetry was noted in 10 (91.0%) of 11 patients, whereas the other patient demonstrated extensor posturing. The Trendelenburg position reversed the symptoms in all patients. The mean sag ratios before, during, and after resolution of brain sag were 0.91 ± 0.03 (mean ± standard error), 1.18 ± 0.03, and 0.91 ± 0.03, respectively. This represented a 30.9% elongation of the brainstem during sag (P < 0.001) and a 23.6% change back to baseline after resolution of the syndrome (P < 0.002). There was no significant difference between the presag and postsag ratios. CONCLUSION:Severe cerebrospinal fluid hypovolemia after craniotomy may produce a dramatic herniation syndrome that is completely reversed by the Trendelenburg position. Brain sag should be included in the differential diagnosis for acute postoperative clinical deterioration in this patient population.