Timothy J. Ingall

A Multinational Comparison of Subarachnoid Hemorrhage Epidemiology in the WHO MONICA Stroke Study

BACKGROUND AND PURPOSE By official, mostly unvalidated statistics, mortality from subarachnoid hemorrhage (SAH) show large variations between countries. Using uniform criteria for case ascertainment and diagnosis, a multinational comparison of attack rates and case fatality rates of SAH has been performed within the framework of the WHO MONICA Project. METHODS In 25- to 64-year-old men and women, a total of 3368 SAH events were recorded during 35.9 million person-years of observation in 11 populations in Europe and China. Strict MONICA criteria were used for case ascertainment and diagnosis of stroke subtype. Case fatality was based on follow-up at 28 days after onset. RESULTS Age-adjusted average annual SAH attack rates varied 10-fold among the 11 populations studied, from 2.0 (95% CI 1.6 to 2.4) per 100 000 population per year in China-Beijing to 22.5 (95% CI 20.9 to 24.1) per 100 000 population per year in Finland. No consistent pattern was observed in the sex ratio of attack rates in the different populations. The overall 28-day case fatality rate was 42%, with 2-fold differences in age-adjusted rates between populations but little difference between men and women. Case fatality rates were consistently higher in Eastern than in Western Europe. CONCLUSIONS Using a uniform methodology, the WHO MONICA Project has shown very large variations in attack rates of SAH across 11 populations in Europe and China. The generally accepted view that women have a higher risk of SAH than men does not apply to all populations. Marked differences in outcome of SAH add to the wide gap in the burden of stroke between East and West Europe.

Has there been a decline in subarachnoid hemorrhage mortality

We studied subarachnoid hemorrhage in the population of Rochester, Minnesota, for the 40-year period from 1945 through 1984. The average annual incidence rate of subarachnoid hemorrhage in Rochester has remained constant at approximately 11 per 100,000 population. Age-specific incidence rates increased with age. However, the average annual mortality rate for subarachnoid hemorrhage in Rochester has shown a decreasing trend, from 6.8 per 100,000 population in 1955-1964 to 4.3 in 1975-1984. It is likely that this is due to a decrease in case-fatality rates from 57% in 1945-1974 to 42% in 1975-1984 (p = 0.10). This decreasing trend was also evident in annual mortality rates from subarachnoid hemorrhage for US white men and women. The reason for the improved case-fatality rate is unclear, but it may be related to changes in management. The interval from onset of subarachnoid hemorrhage to surgery decreased from a median of 12 days in 1975-1979 to 2 days in 1980-1984, and of those who survived to receive medical attention, more patients received some form of medical treatment in 1980-1984. Whether either or both of these changes have led to the decrease in the case-fatality rate is uncertain.

Findings From the Reanalysis of the NINDS Tissue Plasminogen Activator for Acute Ischemic Stroke Treatment Trial

Background and Purpose— Following publication of concerns about the results of the National Institute of Neurological Disorders and Stroke (NINDS) intravenous tissue plasminogen activator (t-PA) in acute stroke treatment trial, NINDS commissioned an independent committee “to address whether there is concern that eligible stroke patients may not benefit from t-PA given according to the protocol used in the trials and, whether the subgroup imbalance (in baseline stroke severity) invalidates the entire trial.” Methods— The original NINDS trial data were reanalyzed to assess the t-PA treatment effect, the effect of the baseline imbalance in stroke severity between the treatment groups on the t-PA treatment effect, and whether subgroups of patients did not benefit from receiving t-PA. Results— A clinically important and statistically significant benefit of t-PA therapy was identified despite subgroup imbalances in baseline stroke severity and an increased incidence of symptomatic intracerebral hemorrhage in t-PA treated patients. The adjusted t-PA to placebo odds ratio (OR) of a favorable outcome was 2.1 (95% CI, 1.5 to 2.9). Although these exploratory analyses found no statistical evidence that the t-PA treatment effect differed among patient subgroups, the study was not powered to detect subgroup treatment differences. Conclusions— These findings support the use of t-PA to treat patients with acute ischemic stroke within 3 hours of onset under the NINDS t-PA trial protocol. Health professionals should work collaboratively to develop guidelines to ensure appropriate use of t-PA in acute ischemic stroke patients.

Duration of cigarette smoking is the strongest predictor of severe extracranial carotid artery atherosclerosis.

The effect of cigarette smoking on extracranial carotid atherosclerosis was studies by obtaining cigarette smoking histories and information on other potential risk factors from consecutive patients undergoing carotid arteriography. At least on extracranial carotid artery was visualized in 752 patients in whom the extent of carotid atherosclerosis was assessed. The total years of cigarette smoking was the most significant independent predictor of the presence of severe carotid atherosclerosis. Other independent predictors, in order of significance, were age, hypertension, diabetes mellitus, male sex, and current systolic blood pressure. By age 60 years, the risk of having severe carotid atherosclerosis for a person who had smoked for 40 years was approximately 3.5 times that for a never smoker. The major benefit of smoking cessation is in limiting the accumulation of smoking years.

Stroke Team Remote Evaluation Using a Digital Observation Camera in Arizona The Initial Mayo Clinic Experience Trial

Background and Purpose— Telemedicine techniques can be used to address the rural–metropolitan disparity in acute stroke care. The Stroke Team Remote Evaluation Using a Digital Observation Camera (STRokE DOC) trial reported more accurate decision making for telemedicine consultations compared with telephone-only and that the California-based research network facilitated a high rate of thrombolysis use, improved data collection, low risk of complications, low technical complications, and favorable assessment times. The main objective of the STRokE DOC Arizona TIME (The Initial Mayo Clinic Experience) trial was to determine the feasibility of establishing, de novo, a single-hub, multirural spoke hospital telestroke research network across a large geographical area in Arizona by replicating the STRokE DOC protocol. Methods— Methods included prospective, single-hub, 2-spoke, randomized, blinded, controlled trial of a 2-way, site-independent, audiovisual telemedicine system designed for remote examination of adult patients with acute stroke versus telephone consultation to assess eligibility for treatment with intravenous thrombolysis. The primary outcome measure was whether the decision to give thrombolysis was correct. Secondary outcomes were rate of thrombolytic use, 90-day functional outcomes, incidence of intracerebral hemorrhages, and technical observations. Results— From December 2007 to October 2008, 54 patients were assessed, 27 of whom were randomized to each arm. Mean National Institutes of Health Stroke Scale score at presentation was 7.3 (SD 6.2) points. No consultations were aborted; however, technical problems (74%) were prevalent in the telemedicine arm. Overall, the correct treatment decision was established in 87% of the consultations. Both modalities, telephone (89% correct) and telemedicine (85% correct), performed well. Intravenous thrombolytic treatment was used in 30% of the telemedicine and telephone consultations. Good functional outcomes at 90 days were not significantly different. There were no statistically significant differences in mortality (4% in telemedicine and 11% in telephone) or rates of intracerebral hemorrhage (4% in telemedicine and 0% in telephone). Conclusions— It is feasible to extend the original STRokE DOC trial protocol to a new state and establish an operational single-hub, multispoke rural hospital telestroke research network in Arizona. The trial was not designed to have sufficient power to detect a difference between the 2 consultative modes: telemedicine and telephone-only. Whether by telemedicine or telephone consultative modalities, there were appropriate treatment decisions, high rates of thrombolysis use, improved data collection, low rates of intracerebral hemorrhage, and equally favorable time requirements. The learning curve was steep for the hub and spoke personnel of the new telestroke network, as reflected by frequent technical problems. Overall, the results support the effectiveness of highly organized and structured stroke telemedicine networks for extending expert stroke care into rural remote communities lacking sufficient neurological expertise.

Smartphone Teleradiology Application Is Successfully Incorporated Into a Telestroke Network Environment

Background and Purpose— ResolutionMD mobile application runs on a Smartphone and affords vascular neurologists access to radiological images of patients with stroke from remote sites in the context of a telemedicine evaluation. Although reliability studies using this technology have been conducted in a controlled environment, this study is the first to incorporate it into a real-world hub and spoke telestroke network. The study objective was to assess the level of agreement of brain CT scan interpretation in a telestroke network between hub vascular neurologists using ResolutionMD, spoke radiologists using a Picture Archiving and Communications System, and independent adjudicators. Methods— Fifty-three patients with stroke at the spoke hospital consented to receive a telemedicine consultation and participate in a registry. Each CT was evaluated by a hub vascular neurologist, a spoke radiologist, and by blinded telestroke adjudicators, and agreement over clinically important radiological features was calculated. Results— Agreement (&kgr; and 95% CI) between hub vascular neurologists using ResolutionMD and (1) the spoke radiologist; and (2) independent adjudicators, respectively, were: identification of intracranial hemorrhage 1.0 (0.92–1.0), 1.0 (0.93–1.0), neoplasm 1.0 (0.92–1.0), 1.0 (0.93–1.0), any radiological contraindication to thrombolysis 1.0 (0.92–1.0), 0.85 (0.65–1.0), early ischemic changes 0.62 (0.28–0.96), 0.58 (0.30–0.86), and hyperdense artery sign 0.40 (0.01–0.80), 0.44 (0.06–0.81). Conclusions— CT head interpretations of telestroke network patients by vascular neurologists using ResolutionMD on Smartphones were in excellent agreement with interpretations by spoke radiologists using a Picture Archiving and Communications System and those of independent telestroke adjudicators using a desktop viewer. Clinical Trial Registration Information— www.clinicaltrials.gov unique identifier NCT00829361.

Thunderclap headache associated with reversible vasospasm and posterior leukoencephalopathy syndrome

A 46-year-old woman with a past medical history of episodic migraine and benign sexual headache was in good health until she experienced an explosive, sudden and severe occipital headache while having a bowel movement. There was no associated loss of consciousness or awareness. The headache, however, was associated with nausea and neck pain/ stiffness. The headache intensity diminished over several hours. Two days later, she experienced a recurrent more prolonged thunderclap headache, whereupon she was taken immediately to hospital. In the emergency department (ED), she was hypertensive (190–200/110–120) and mildly drowsy. Examination revealed no meningeal, long tract, focal, or lateralizing neurological signs. Furthermore, there was no evidence of hypertensive retinopathy or papilloedema. During her evaluation in the ED, she had a witnessed generalized tonic clonic seizure. A computed tomography (CT) scan of the brain and lumbar puncture were normal. Blood work revealed a mild thrombocytosis (437K), but CBC, electrolytes, ESR (9), ANA (0.4), hypercoagulable profile, TSH, urinalysis, and serum chemistry were normal. A magnetic resonance imaging (MRI) scan of the brain revealed T2 signal abnormalities in the posterior parietooccipital lobes with a small area of increased diffusion-weighted signal in the left occipital lobe (Figs. 1 and 2). There was no evidence of gadolinium enhancement. On the fourth hospital day, a fourvessel cerebral angiogram revealed diffuse multifocal vasospasm involving the posterior and anterior circulation (Fig. 3). There was no evidence of an intracranial aneurysm or arteriovenous malformation. A diagnosis of ischaemic stroke secondary to CNS vasculitis was made and the patient was treated with high-dose intravenous methylprednisolone and warfarin. The patient was transferred to our institution for in-patient video-EEG monitoring because of the generalized tonic-clonic seizure. During her hospitalization at our institution, follow-up MRI scans (on days 6 and 13 after presentation) revealed resolution of the T2 signal abnormalities (Fig. 4). Fifteen days after presentation, a follow-up magnetic resonance angiogram was normal. The patient was treated with lisinopril 5 mg, her blood pressure ranged from 130 to 140 systolic and 80 to 90 diastolic. No further seizures occurred and video-EEG monitoring over 48 h was normal. An evaluation for secondary causes of hypertension was unremarkable. Warfarin was discontinued and the patient was discharged in normal neurological condition and headache free. She remained asymptomatic on lisinopril 4 months later.

Serum Lipids and Lipoproteins Are Less Powerful Predictors of Extracranial Carotid Artery Atherosclerosis Than Are Cigarette Smoking and Hypertension

The effect of serum lipids and lipoproteins on extracranial carotid artery atherosclerosis (CAS) was studied in patients who underwent carotid arteriography. Serum lipid and lipoprotein values along with data on other potential predictors of extracranial CAS were determined in 240 patients who had at least one extracranial carotid artery visualized. In a multiple logistic regression analysis, the independently significant predictors of the presence of extracranial CAS were, in decreasing order of significance, duration of smoking of cigarettes, hypertension, age, and low-density lipoprotein cholesterol. Serum cholesterol, triglycerides, high-density lipoprotein cholesterol, and apolipoprotein A-I did not show an independent effect. Although low-density lipoprotein cholesterol was an independent predictor of the presence of extracranial CAS, its effect as a predictor was far outweighed by the effects of the duration of smoking of cigarettes and a history of hypertension.

Management of Acute Ischemic Stroke

The treatment of acute ischemic stroke has evolved from observation and the passage of time dictating outcome to an approach that emphasizes time from ictus, rapid response, and a dedicated treatment team. We review the treatment of acute ischemic stroke from the prehospital setting, to the emergency department, to the inpatient hospital setting. We discuss the importance of prehospital assessment and treatment, including the use of elements of the neurologic examination, recognition of symptoms that can mimic those of acute ischemic stroke, and rapid transport of patients who are potential candidates for thrombolytic therapy to hospitals with that capability. Coordinated management of acute ischemic stroke in the emergency department is critical as well, beginning with non-contrast-enhanced computed tomography of the brain. The advantages of a multidisciplinary dedicated stroke team are discussed, as are thrombolytic therapy and other inpatient treatment options. Finally, we cover evolving management strategies, treatments, and tools that could improve patient outcomes.

Preventing ischemic stroke. Current approaches to primary and secondary prevention.

PREVIEW Since few patients are eligible to receive intravenous tissue plasminogen activator, the only approved treatment for acute stroke, prevention is the most important treatment strategy to reduce the burden of the disease. Numerous risk factors for stroke have been identified, and modification of these factors is the crux of primary prevention. In this article, Dr Ingall provides an overview of the data regarding the roles of both risk factor modification and medications in the primary and secondary prevention of ischemic stroke.