Daryl R. Gress

Revised and Updated Recommendations for the Establishment of Primary Stroke Centers: A Summary Statement From the Brain Attack Coalition

Background and Purpose— The formation and certification of Primary Stroke Centers has progressed rapidly since the Brain Attack Coalitions original recommendations in 2000. The purpose of this article is to revise and update our recommendations for Primary Stroke Centers to reflect the latest data and experience. Methods— We conducted a literature review using MEDLINE and PubMed from March 2000 to January 2011. The review focused on studies that were relevant for acute stroke diagnosis, treatment, and care. Original references as well as meta-analyses and other care guidelines were also reviewed and included if found to be valid and relevant. Levels of evidence were added to reflect current guideline development practices. Results— Based on the literature review and experience at Primary Stroke Centers, the importance of some elements has been further strengthened, and several new areas have been added. These include (1) the importance of acute stroke teams; (2) the importance of Stroke Units with telemetry monitoring; (3) performance of brain imaging with MRI and diffusion-weighted sequences; (4) assessment of cerebral vasculature with MR angiography or CT angiography; (5) cardiac imaging; (6) early initiation of rehabilitation therapies; and (7) certification by an independent body, including a site visit and disease performance measures. Conclusions— Based on the evidence, several elements of Primary Stroke Centers are particularly important for improving the care of patients with an acute stroke. Additional elements focus on imaging of the brain, the cerebral vasculature, and the heart. These new elements may improve the care and outcomes for patients with stroke cared for at a Primary Stroke Center.

A comparison of risk factors for recurrent TIA and stroke in patients diagnosed with TIA

Background: Some spells consistent with TIA may be benign, such as those produced by migraine or migraine accompaniments in the elderly. Distinguishing these from embolic or thrombotic events may be difficult. Methods: Emergency department physicians identified patients who presented with a presumed TIA at one of 16 hospitals in Northern California from March 1997 through February 1998. Recurrent TIAs and strokes were recorded for 90 days afterwards. Results: Of 1,707 patients in whom TIA had been diagnosed in the emergency department, 191 (11.2%) had a recurrent TIA and 180 (10.5%) had a stroke during 90-day followup. Independent risk factors for recurrent TIA were age >60 years (odds ratio 1.9; 95% CI 1.2 to 2.9; p = 0.003), history of multiple TIAs (odds ratio 2.9; 2.1 to 4.0; p < 0.001), duration of spell ≤10 minutes (odds ratio 2.3; 1.6 to 3.3; p < 0.001), and sensory abnormality associated with the spell (odds ratio 1.9; 1.4 to 2.6; p < 0.001). Independent risk factors for stroke from a previous analysis were age, duration >10 minutes, diabetes, weakness, and speech impairment. Among the 30 patients with isolated sensory symptoms lasting ≤10 minutes, the risk of recurrent TIA was 40% and none had a stroke. Conclusions: In patients in whom TIA has been diagnosed in the emergency department, risk factors for subsequent stroke and recurrent TIA are different. A subset of patients with presumed TIA has a benign short-term course with multiple brief TIAs more frequently characterized by sensory symptoms.

Patients in poor neurological condition after subarachnoid hemorrhage: early management and long-term outcome.

SummaryWe report management and outcome data on 118 patients that presented to our emergency room over a 4 year interval (1990–1994) in poor neurological condition after subarachnoid hemorrhage. All patients were treated following a strict protocol. After initial evaluation, patients underwent a head computerized tomography (CT) scan to try to understand the mechanism of coma. If CT did not show destruction of vital brain areas, a ventriculostomy was inserted and ICP measured. If ICP was less than 20 mm Hg, or if standard treatment of increased ICP was able to lower the ICP to a value less than 20 mmHg, patients were evaluated with cerebral angiogram to determine the location of the raptured aneurysm. The lesion was then treated by craniotomy for aneurysm clipping or endovascular obliteration. Postoperative monitoring for vasospasm with clinical exam and transcranial doppler studies was performed routinely. If vasospasm developed, this was managed aggressively with hypertensive, hypervolemic and hemodilutional therapy and, at times, endovascular treatment with angioplasty or papaverine. Outcome was measured at 1 year or more after treatment. Among patients who met criteria for aneurysm treatment, 47% had excellent or good neurologic outcome. There was a 30% mortality rate in these patients. In patients with high ICP, poor brainstem function or destruction of vital brain areas on CT, comfort measures only were offered and almost all died. It is concluded that an approach of early aneurysm obliteration and aggressive medical and endovascular management of vasospasm is warranted in patients in poor neurological conditions after subarachnoid hemorrhage.

The Safety and Efficacy of Cyclosporine A in the Prevention of Vasospasm in Patients with Fisher Grade 3 Subarachnoid Hemorrhages: A Pilot Study

OBJECTIVE To evaluate the safety and any potential effect of cyclosporine A (CycA) in preventing cerebral vasospasm. METHODS Nine patients with Fisher Grade 3 subarachnoid hemorrhages were studied. After a loading dose of 7.5 mg/kg of CycA was administered every 12 hours for two doses, enteral treatment with CycA was started within 72 hours of the onset of the subarachnoid hemorrhage. Whole blood CycA levels were titrated to maintain levels of 50 to 400 ng/kg. Transcranial doppler ultrasonography was performed daily. Middle cerebral artery velocities were used to assess the degree of vasospasm. Angiography was performed to confirm the vasospasm in symptomatic patients, or it was performed if transcranial doppler ultrasonograms were unobtainable. Patients were treated with a standard pharmacological regimen of nimodipine. Induced hypertension, hemodilution, and hypervolemia were instituted at the discretion of the neurosurgical team. Intra-arterial papaverine was infused into the vasospastic vessels of three recalcitrant patients. Outcome was assessed at 6 months with the Glasgow Outcome Scale. RESULTS All the patients displayed evidence of vessel narrowing, which was disclosed by transcranial doppler ultrasonography or angiography. Five patients developed ischemic deficits, two were treated with intra-arterial papaverine, and three died of complications secondary to vasospasm. No significant hepatic, renal, or infectious complication developed as a result of the administration of CycA. CONCLUSIONS CycA proved safe to use but failed to prevent the development of cerebral vasospasm or delayed ischemic deficits in patients considered at high risk.

Effect of low-intensity warfarin anticoagulation on level of activity of the hemostatic system in patients with atrial fibrillation. BAATAF Investigators.

BACKGROUND AND PURPOSE The Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF) demonstrated that low-intensity warfarin anticoagulation can, with safety, sharply reduce the rate of stroke in patients with nonvalvular atrial fibrillation. The beneficial effect of warfarin was presumably related to a decrease in clot formation in the cardiac atria and subsequent embolization. METHODS To assess the effect of warfarin therapy on in vivo clotting in patients in the BAATAF, we measured the plasma level of prothrombin activation fragment F1+2. One sample was obtained from 125 patients from the BAATAF; 62 were taking warfarin and 63 were not taking warfarin (control group). RESULTS The warfarin group had a 71% lower mean F1+2 level than the control group (mean F1+2 of 1.57 nmol/L in the control group compared with a mean of 0.46 nmol/L in the warfarin group; P < .001). F1+2 levels were higher in older subjects but were consistently lower in the warfarin group at all ages. Fifty-two percent of patients in the control group were taking chronic aspirin therapy at the time their F1+2 level was measured. Control patients taking aspirin had F1+2 levels very similar to control patients not taking aspirin (mean of 1.52 nmol/L for control patients on aspirin compared with 1.64 nmol/L for control patients off aspirin; P > .1). CONCLUSIONS We conclude that prothrombin activation was significantly suppressed in vivo by warfarin but not aspirin among patients in the BAATAF. These findings correlate with the marked reduction in ischemic stroke noted among patients in the warfarin treatment group observed in the BAATAF.

Formation and Function of Acute Stroke–Ready Hospitals Within a Stroke System of Care Recommendations From the Brain Attack Coalition

Background and Purpose— Many patients with an acute stroke live in areas without ready access to a Primary or Comprehensive Stroke Center. The formation of care facilities that meet the needs of these patients might improve their care and outcomes and guide them and emergency responders to such centers within a stroke system of care. Methods— The Brain Attack Coalition conducted an electronic search of the English medical literature from January 2000 to December 2012 to identify care elements and processes shown to be beneficial for acute stroke care. We used evidence grading and consensus paradigms to synthesize recommendations for Acute Stroke–Ready Hospitals (ASRHs). Results— Several key elements for an ASRH were identified, including acute stroke teams, written care protocols, involvement of emergency medical services and emergency department, and rapid laboratory and neuroimaging testing. Unique aspects include the use of telemedicine, hospital transfer protocols, and drip and ship therapies. Emergent therapies include the use of intravenous tissue-type plasminogen activator and the reversal of coagulopathies. Although many of the care elements are similar to those of a Primary Stroke Center, compliance rates of ≥67% are suggested in recognition of the staffing, logistical, and financial challenges faced by rural facilities. Conclusions— ASRHs will form the foundation for acute stroke care in many settings. Recommended elements of an ASRH build on those proven to improve care and outcomes at Primary Stroke Centers. The ASRH will be a key component for patient care within an evolving stroke system of care.

Safety and pharmacokinetics of sodium nitrite in patients with subarachnoid hemorrhage: a Phase IIA study

OBJECT Intravenous sodium nitrite has been shown to prevent and reverse cerebral vasospasm in a primate model of subarachnoid hemorrhage (SAH). The present Phase IIA dose-escalation study of sodium nitrite was conducted to determine the compounds safety in humans with aneurysmal SAH and to establish its pharmacokinetics during a 14-day infusion. Methods In 18 patients (3 cohorts of 6 patients each) with SAH from a ruptured cerebral aneurysm, nitrite (3 patients) or saline (3 patients) was infused. Sodium nitrite and saline were delivered intravenously for 14 days, and a dose-escalation scheme was used for the nitrite, with a maximum dose of 64 nmol/kg/min. Sodium nitrite blood levels were frequently sampled and measured using mass spectroscopy, and blood methemoglobin levels were continuously monitored using a pulse oximeter. RESULTS In the 14-day infusions in critically ill patients with SAH, there was no toxicity or systemic hypotension, and blood methemoglobin levels remained at 3.3% or less in all patients. Nitrite levels increased rapidly during intravenous infusion and reached steady-state levels by 12 hours after the start of infusion on Day 1. The nitrite plasma half-life was less than 1 hour across all dose levels evaluated after stopping nitrite infusions on Day 14. CONCLUSIONS Previous preclinical investigations of sodium nitrite for the prevention and reversal of vasospasm in a primate model of SAH were effective using doses similar to the highest dose examined in the current study (64 nmol/kg/min). Results of the current study suggest that safe and potentially therapeutic levels of nitrite can be achieved and sustained in critically ill patients after SAH from a ruptured cerebral aneurysm.

Rapid response to acyclovir in herpes zoster-associated encephalitis

A previously healthy patient became acutely encephalopathic, with complete disorientation and amnesia, several days after the onset of thoracic herpes zoster. She had transiently abnormal electroencephalographic results, abnormalities on radionuclide brain scanning, and cerebrospinal fluid pleocytosis. There was no evidence of a toxic/metabolic encephalopathy except for a mildly elevated ammonia level. Intravenously administered acyclovir (30 mg/kg per day) induced a dramatic response, with complete resolution of the encephalopathy within 72 hours and normalization of the electroencephalographic results. The scant clinical experience with the successful use of acyclovir in the treatment of herpes zoster-associated encephalitis is reviewed.

Extracranial vertebral artery pseudoaneurysm presenting as subarachnoid hemorrhage.

Background and Purpose True aneurysms of the extracranial vertebral artery are rare. The usual pathogenesis of aneurysms in this location is either penetrating or blunt trauma with resultant pseudoaneurysm formation. We report a postpartum patient with a presumed traumatic pseudoaneurysm of the extracranial vertebral artery presenting with subarachnoid hemorrhage. Case Description A 41-year-old woman had three episodes of neck stiffness 1 month after an uncomplicated vaginal delivery. The last episode, 3 days before admission, was accompanied by intense neck and head pain and paresthesias that extended into the left arm, thumb, and forefinger. Results Lumbar puncture showed subarachnoid hemorrhage. Angiography revealed a left vertebral artery dissection from C6-7 to C3 with pseudoaneurysm at C5-6. Computed tomography demonstrated impingement of the C6 root at the foramen by this lesion. The lesion was successfully treated by balloon occlusion of the vertebral artery. Conclusions We present a patient with an extracranial vertebral pseudoaneurysm with subarachnoid hemorrhage and cervical root impingement. To our knowledge, this is the first case of such a lesion presenting as subarachnoid hemorrhage. The lesion was successfully treated using endovascular techniques.

Computerized Tomography and Clinical Features of Large Cerebral Hemorrhages

We studied 17 consecutive patients with nonaneurysmal cerebral hemorrhages larger than 55 cm3 to determine the computerized tomographic correlates of stupor and coma. Coma was associated wi