Hans-Christian Koennecke

Morbidity of Intracranial Hemorrhage in Patients With Cerebral Arteriovenous Malformation

To the Editor: nnThe Columbia-Presbyterian Medical Center Arteriovenous Malformation Study Project has made, and continues to make, a significant contribution to our understanding of arteriovenous malformations of the brain. In the recent contribution of Hartmann et al,1 a number of interesting observations were made with regard to hemorrhage. The first is the high incidence among those that bleed of subarachnoid and intraventricular hemorrhage. Only 54% of initial hemorrhages and 49% of follow-up hemorrhage were intraparenchymal. This is at considerable variance with our experience at the Northern and Western Medical School, The University of Sydney, where we have followed all arteriovenous malformations (AVMs) seen since 1991, and of 114 patients presenting with hemorrhage, 82% have a significant intraparenchymal component.nnOne is left with the feeling from this article that hemorrhage from AVMs is relatively benign. However, it must be borne in mind that this is a specially selected subset …

Feeding Artery Pressure and Venous Drainage Pattern Are Primary Determinants of Hemorrhage From Cerebral Arteriovenous Malformations

PURPOSEnThe purpose of this study was to define the influence of feeding mean arterial pressure (FMAP) in conjunction with other morphological or clinical risk factors in determining the probability of hemorrhagic presentation in patients with cerebral arteriovenous malformations (AVMs).nnnMETHODSnClinical and angiographic data from 340 patients with cerebral AVMs from a prospective database were reviewed. Patients were identified in whom FMAP was measured during superselective angiography. Additional variables analyzed included AVM size, location, nidus border, presence of aneurysms, and arterial supply and venous drainage patterns. The presence of arterial aneurysms was also correlated with site of bleeding on imaging studies.nnnRESULTSnBy univariate analysis, exclusively deep venous drainage, periventricular venous drainage, posterior fossa location, and FMAP predicted hemorrhagic presentation. When we used stepwise multiple logistic regression analysis in the cohort that had FMAP measurements (n = 129), only exclusively deep venous drainage (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.4 to 9.8) and FMAP (OR, 1.4 per 10 mm Hg increase; 95% CI, 1.1 to 1.8) were independent predictors (P < 0.01) of hemorrhagic presentation; size, location, and the presence of aneurysms were not independent predictors. There was also no association (P = 0.23) between the presence of arterial aneurysms and subarachnoid hemorrhage.nnnCONCLUSIONSnHigh arterial input pressure (FMAP) and venous outflow restriction (exclusively deep venous drainage) were the most powerful risk predictors for hemorrhagic AVM presentation. Our findings suggest that high intranidal pressure is more important than factors such as size, location, and the presence of arterial aneurysms in the pathophysiology of AVM hemorrhage.

Factors influencing in-hospital mortality and morbidity in patients treated on a stroke unit

Objective: To determine the extent that demographics, clinical characteristics, comorbidities, and complications contribute to the risk of in-hospital mortality and morbidity in acute stroke. Methods: Data of consecutive patients admitted to 14 stroke units cooperating within the Berlin Stroke Register were analyzed. The association of demographics, clinical characteristics, comorbidities, and complications with the risk of in-hospital death and poor outcome at discharge was assessed, and independent attributable risks were calculated, applying average sequential attributable fractions. Results: In a 3-year period, 16,518 consecutive patients with ischemic or hemorrhagic stroke were documented. In-hospital mortality was 5.4%, and 45.7% had a poor outcome (modifed Rankin Scale score ≥3). In patients with length of stay (LOS) ≤7 days, 37.5% of in-hospital deaths were attributed to stroke severity, 23.1% to sociodemographics (age and prestroke disability), and 28.9% to increased intracranial pressure (iICP) and other complications. In those with LOS >7 days, age and stroke severity accounted for 44.1%, whereas pneumonia (12.2%), other complications (12.6%), and iICP (8.3%) contributed to one-third of in-hospital deaths. For poor outcome, attributable risks were similar for prestroke disability, stroke severity, pneumonia, and other complications regardless of the patients LOS. Conclusions: Approximately two-thirds of early death and poor outcome in acute stroke is attributed to nonmodifiable predictors, whereas main modifiable factors are early complications such as iICP, pneumonia, or other complications, on which stroke unit treatment should focus to further improve the prognosis of acute stroke.

Intravenous tPA for Ischemic Stroke Team Performance Over Time, Safety, and Efficacy in a Single-Center, 2-Year Experience

Background and Purpose Safety and efficacy concerns toward thrombolysis for ischemic stroke prevail among many neurologists because of the risks of hemorrhage and the small proportion of suitable patients. We therefore prospectively assessed feasibility, safety, efficacy, and team performance in a single center to prove whether thrombolytic treatment is practical in daily clinical routine. Methods Patients were prospectively recruited over a 2-year period. Major inclusion and exclusion criteria from large, randomized controlled trials were combined. Prespecified outcome parameters were the modified Rankin scale (MRS) and the Barthel Index (BI) at 3 months and symptomatic hemorrhagic complications. In addition, certain time intervals during the diagnostic process preceding thrombolysis were prospectively recorded. Results Within 2 years a total of 75 patients underwent intravenous thrombolysis, corresponding to 9.4% of all admitted patients with stroke and 14.9% of patients with ischemic stroke. Mean±SD age was 68±13 (range 34 to 90) years; median baseline National Institutes of Health Stroke Scale score was 13±6 (range 2 to 34). Thrombolysis was started at an average time of 144 minutes after symptom onset, and 13 patients (17.3%) were treated beyond 3 hours. Two cerebral hemorrhages (2.7%) occurred. Outcome according to the MRS was good (MRS 0 to 1) in 40%, moderate (MRS 2 to 3) in 32%, and poor (MRS 4 to 5) in 13%; the corresponding results, as measured by the BI, were 61% (BI 95 to 100, good), 16% (BI 55 to 90, moderate), and 8% (BI 0 to 50, poor). The mortality rate was 15%. Over 2 years the median door-to-CT time decreased from 30 to 22 minutes (27%), and the door-to-needle time was shortened from 96 to 73 minutes (14%). The mean number of patients treated per month increased from 2 to 4. Conclusions Thrombolytic therapy can be performed safely and efficaciously in daily clinical routine. More than a minority of acute stroke patients might be eligible for intravenous thrombolysis. The performance of a stroke team can be improved over time, subsequently increasing the proportion of eligible patients and thereby the efficiency of the method.

Acetaminophen for Altering Body Temperature in Acute Stroke: A Randomized Clinical Trial * Editorial Comment: A Randomized Clinical Trial

Background and Purpose— Mild alterations in temperature have prominent effects on ischemic cell injury and stroke outcome. Elevated core body temperature (CBT), even if mild, may exacerbate neuronal injury and worsen outcome, whereas hypothermia is potentially neuroprotective. The antipyretic effects of acetaminophen were hypothesized to reduce CBT. Methods— This was a randomized, controlled clinical trial at 2 university hospitals. Patients were included if they had stroke within 24 hours of onset of symptoms, National Institutes of Health Stroke Scale (NIHSS) score ≥5, initial CBT <38.5°C, and white blood cell count <12 600 cells/mm3; they were excluded if they had signs of infection, severe medical illness, or contraindication to acetaminophen. CBT was measured every 30 minutes. Patients were randomized to receive acetaminophen 650 mg or placebo every 4 hours for 24 hours. The primary outcome measure was mean CBT during the 24-hour study period; the secondary outcome measure was the change in NIHSS. Results— Thirty-nine patients were randomized. Baseline CBT was the same: 36.96°C for acetaminophen versus 36.95°C for placebo (P =0.96). During the study period, CBT tended to be lower in the acetaminophen group (37.13°C versus 37.35°C), a difference of 0.22°C (95% CI, −0.08°C to 0.51°C;P =0.14). Patients given acetaminophen tended to be more often hypothermic <36.5°C (OR, 3.4; 95% CI, 0.83 to 14.2;P =0.09) and less often hyperthermic >37.5°C (OR, 0.52; 95% CI, 0.19 to 1.44;P =0.22). The change in NIHSS scores from baseline to 48 hours did not differ between the groups (P =0.93). Conclusions— Early administration of acetaminophen (3900 mg/d) to afebrile patients with acute stroke may result in a small reduction in CBT. Acetaminophen may also modestly promote hypothermia <36.5°C or prevent hyperthermia >37.5°C. These effects are unlikely to have robust clinical impact, and alternative or additional methods are needed to achieve effective thermoregulation in stroke patients.

Microemboli on Transcranial Doppler in Patients with Spontaneous Carotid Artery Dissection

High‐intensity transient signals on transcranial Doppler sonography (TCD) are associated with atherosclerotic stenosis of the internal carotid artery. Few data exist regarding the detection of high‐intensity transient signals in dissected carotid arteries. In the present study, 6 patients with spontaneous carotid dissection, defined by magnetic resonance techniques and duplex sonography, were examined by TCD. Both middle cerebral arteries were monitored simultaneously for 30 minutes. Four of the patients had ipsilateral cerebral ischemia, while 2 presented with other symptoms. High‐intensity transient signals were detected in the middle cerebral artery ipsilateral to the dissection in 3 of the 4 patients with cerebral ischemia and in none of the patients with other presenting symptoms. No microemboli were found contralateral to the dissected arteries. Microemboli can be detected distally from dissected carotid arteries. The present findings support the assumption that embolism is a major cause of stroke in patients with carotid dissection, and suggest that high‐intensity transient signals are more common among patients with cerebral ischemia secondary to dissection.

Scattered Brain Infarct Pattern on Diffusion-Weighted Magnetic Resonance Imaging in Patients with Acute Ischemic Stroke

Background and Purpose: Infarct patterns on brain imaging contribute to the etiologic classification of ischemic stroke. However, the association of specific subtypes of infarcts and etiologic mechanisms is often weak, and acute lesions are frequently missed on initial computed tomography (CT). Diffusion-weighted imaging (DWI) is superior in visualizing acute ischemic lesions as compared to CT and conventional magnetic resonance imaging (MRI). In our prospective study, we addressed the question whether a distinct pattern of infarction on DWI is associated with infarct etiology and clinical outcome. Methods: Sixty-two patients with clinical signs of acute ischemic stroke and negative acute CT upon admission underwent DWI within 10 days after the ictus. Neurological status was documented using the NIH stroke scale. A scattered lesion pattern was defined by at least 2 separate hyperintense DWI lesions within the territory of one of the major cerebral arteries. Ischemic lesions were defined as acute if the region was demarcated strongly hyperintense in all DW images, and if the apparent diffusion coefficient was below normal. Results: In 32 patients, DWI revealed a scattered lesion pattern, while in 30 patients a single acute lesion was detected. In patients with scattered lesions, potential arterial or cardiac embolic sources were detected in 26 patients (81.3%), as compared to 5 patients (16.6%) in the group with single lesions (χ2 test, p < 0.0001). The neurological status of patients with scattered lesions improved significantly more than among patients with single lesions (Mann-Whitney test, p < 0.0003). Conclusion: A scattered lesion pattern on DWI in patients with acute brain infarction and negative initial CT scan is associated with an embolic etiology and may indicate a favorable clinical outcome.

Association Between Socioeconomic Status and Functional Impairment 3 Months After Ischemic Stroke The Berlin Stroke Register

Background and Purpose— We aimed to analyze the association between patient socioeconomic status and functional impairment 3 months after ischemic stroke and to identify factors that influence this association. Methods— Data were obtained from the Berlin Stroke Register, a network of 14 stroke units in Berlin. Ischemic stroke patients consecutively admitted to 1 of the hospitals in the Berlin Stroke Register between June 2010 and September 2011, were followedup 3 months after the index event by postal or telephone interview. We used multivariable logistic regression to examine the association between highest education as marker of socioeconomic status and functional impairment after stroke defined by Barthel Index categories. We adjusted for age, sex, prestroke dependency, stroke severity, functional deficit after stroke onset, and comorbidities as possible confounding factors. Results— A total of 1688 ischemic stroke patients who were alive at 3 months and completed the questionnaire were included in the analysis; 40% of the patients were female and 50% of the patients were 70 years or older. Age, prestroke dependency, stroke severity, and the absence of comorbidities were significantly associated with good functional outcome at 3 months. In multivariable analysis, a higher probability of good outcome was observed in patients with college or university degree (odds ratio, 2.18; 95% confidence interval, 1.39–3.42) compared with patients with no completed education. Conclusion— Patients with lower education have considerably lower rates of good functional outcome after stroke that cannot be fully explained by variations in the patients’ clinical and demographic characteristics.

Influence of Acute Complications on Outcome 3 Months after Ischemic Stroke

Background Early medical complications are potentially modifiable factors influencing in-hospital outcome. We investigated the influence of acute complications on mortality and poor outcome 3 months after ischemic stroke. Methods Data were obtained from patients admitted to one of 13 stroke units of the Berlin Stroke Registry (BSR) who participated in a 3-months-follow up between June 2010 and September 2012. We examined the influence of the cumulative number of early in-hospital complications on mortality and poor outcome (death, disability or institutionalization) 3 months after stroke using multivariable logistic regression analyses and calculated attributable fractions to determine the impact of early complications on mortality and poor outcome. Results A total of 2349 ischemic stroke patients alive at discharge from acute care were included in the analysis. Older age, stroke severity, pre-stroke dependency and early complications were independent predictors of mortality 3 months after stroke. Poor outcome was independently associated with older age, stroke severity, pre-stroke dependency, previous stroke and early complications. More than 60% of deaths and poor outcomes were attributed to age, pre-stroke dependency and stroke severity and in-hospital complications contributed to 12.3% of deaths and 9.1% of poor outcomes 3 months after stroke. Conclusion The majority of deaths and poor outcomes after stroke were attributed to non-modifiable factors. However, early in-hospital complications significantly affect outcome in patients who survived the acute phase after stroke, underlining the need to improve prevention and treatment of complications in hospital.

Diffusion‐weighted magnetic resonance imaging in two patients with polycythemia rubra vera and early ischemic stroke

Polycythemia rubra vera (PRV) is a rare myeloproliferative disorder with a high risk of ischemic stroke. Although thrombosis of large cerebral arteries is the most frequently presumed pathomechanism, various infarct patterns have been described in patients with PRV and ischemic stroke. We report two patients with mild acute ischemic strokes and known PRV, in whom a scattered lesion pattern was detected by diffusion‐weighted magnetic resonance imaging (DWI), but was not visible on computed tomography (CT) and conventional magnetic resonance imaging (MRI). Further diagnostic work‐up including extra‐ and transcranial Doppler sonography (ECD, TCD), transesophageal echocardiography (TEE), magnetic resonance angiography and Holter monitoring revealed no obvious sources of cerebral embolism in both cases. However, TEE in one patient demonstrated spontaneous echo contrast (SEC) in the left atrium. In both patients the symptomatology resolved completely. The detection of a scattered infarct pattern by DWI in patients with PRV and acute ischemic stroke has not been reported previously. DWI findings together with the SEC in one patient emphasize the assumption that a prothrombotic state with subsequent arterial embolism rather than local arterial thrombosis may be the underlying pathomechanism of stroke in some patients with PRV. Adding DWI to the diagnostic work‐up may help to clarify etiology in patients with PRV and acute ischemic stroke.