Alexander B. Baxter

Withdrawal of support in intracerebral hemorrhage may lead to self-fulfilling prophecies

Background: Withdrawal of support in patients with severe brain injury invariably leads to death. Preconceived notions about futility of care in patients with intracerebral hemorrhage (ICH) may prompt withdrawal of support, and modeling outcome in patient populations in whom withdrawal of support occurs may lead to self-fulfilling prophecies. Methods: Subjects included consecutive patients with supratentorial ICH. Radiographic characteristics of the hemorrhage, clinical variables, and neurologic outcome were assessed. Attitudes about futility of care were examined among members of the departments of neurology and neurologic surgery through a written survey and case presentations. Results: There were 87 patients with supratentorial ICH; overall mortality was 34.5% (30/87). Mortality was 66.7% (18/27) in patients with Glasgow Coma Score ≤8 and ICH volume >60 cm3. Medical support was withdrawn in 76.7% (23/30) of patients who died. Inclusion of a variable to account for the withdrawal of support in a model predicting outcome negated the predictive value of all other variables. Patients undergoing surgical decompression were unlikely to have support withdrawn, and surgery was less likely to be performed in older patients (p < 0.01) and patients with left hemispheric hemorrhage (p = 0.04). Survey results suggested that practitioners tend to be overly pessimistic in prognosticating outcome based upon data available at the time of presentation. Conclusions: The most important prognostic variable in determining outcome after ICH is the level of medical support provided. Withdrawal of support in patients felt likely to have a “poor outcome” biases predictive models and leads to self-fulfilling prophecies. Our data show that individual patients in traditionally “poor outcome” categories can have a reasonable neurologic outcome when treated aggressively.

Extravasation of Radiographic Contrast Is an Independent Predictor of Death in Primary Intracerebral Hemorrhage

BACKGROUND AND PURPOSE Hematomas that enlarge following presentation with primary intracerebral hemorrhage (ICH) are associated with increased mortality, but the mechanisms of hematoma enlargement are poorly understood. We interpreted the presence of contrast extravasation into the hematoma after CT angiography (CTA) as evidence of ongoing hemorrhage and sought to identify the clinical significance of contrast extravasation as well as factors associated with the risk of extravasation. METHODS We reviewed the clinical records and radiographic studies of all patients with intracranial hemorrhage undergoing CTA from 1994 to 1997. Only patients with primary ICH were included in this study. Univariate and multivariate logistic regression analyses were performed to determine the associations between clinical and radiological variables and the risk of hospital death or contrast extravasation. RESULTS Data were available for 113 patients. Contrast extravasation was seen in 46% of patients at the time of CTA, and the presence of contrast extravasation was associated with increased fatality: 63.5% versus 16.4% in patients without extravasation (P=0.011). There was a trend toward a shorter time (median+/-SD) from symptom onset to CTA in patients with extravasation (4.6+/-19 hours) than in patients with no evidence of extravasation (6.6+/-28 hours; P=0.065). Multivariate analysis revealed that hematoma size (P=0.022), Glasgow Coma Scale (GCS) score (P=0.016), extravasation of contrast (P=0.006), infratentorial ICH (P=0.014), and lack of surgery (P<0.001) were independently associated with hospital death. Variables independently associated with contrast extravasation were hematoma size (P=0.024), MABP >120 mm Hg (P=0.012), and GCS score of </=8 (P<0.005). CONCLUSIONS Contrast extravasation into the hematoma after ICH is associated with increased fatality. The risk of contrast extravasation is increased with extreme hypertension, depressed consciousness, and large hemorrhages. If contrast extravasation represents ongoing hemorrhage, the findings in this study may have implications for therapy of ICH, particularly with regard to blood pressure management.

AUR Memorial Award 1991. Immunogenicity of gadolinium-based contrast agents for magnetic resonance imaging. Induction and characterization of antibodies in animals.

To evaluate the immunogenic potential of gadolinium-based magnetic resonance imaging (MRI) contrast agents, Sprague-Dawley rats were sensitized with gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) dimeglumine and with Gd-DTPA covalently linked to either human serum albumin, dextran, or polylysine. IgG antibodies directed against Gd-DTPA were detected in immune sera by an enzyme-linked immunosorbent assay (ELISA), and were confirmed by competitive inhibition of antibody binding using free Gd-DTPA dimeglumine. Antiserum induced by immunization with human serum albumin-(Gd-DTPA) was characterized by a monophasic competition curve with 50% inhibition (IC50) = 5.5 x 10(-4) M when Gd-DTPA dimeglumine was used as both the well-coating and the displacing agent in a competition ELISA. Antiserum induced by Gd-DTPA dimeglumine alone was characterized by a biphasic competition curve with IC50 = 6.5 x 10(-7) M and 7.9 x 10(-4) M. Antisera obtained after exposure to either dextran-(Gd-DTPA) or polylysine-(Gd-DTPA) were of insufficient titer for characterization. The detection of antibodies specific for Gd-DTPA suggests in vivo protein binding with formation of hapten-carrier conjugates. This hypothesis is supported by increased relaxivity values observed when Gd-DTPA dimeglumine is incubated in serum rather than in water. Gd-DTPA dimeglumine and albumin-(Gd-DTPA) are immunogenic in rats under idealized experimental conditions. Additional studies will be necessary to determine the potential for immunologic response in humans to gadolinium chelates under conditions of exposure inherent in clinical use.

In vitro histamine release induced by magnetic resonance imaging and iodinated contrast media.

RATIONALE AND OBJECTIVES.To investigate the mechanism of anaphylactoid reactions to contrast media, in vitro histamine release induced by magnetic resonance imaging, and iodinated contrast agents was examined in a dog mastocytoma cell line. METHODS.Two gadolinium (Gd)-based magnetic resonance contrast agents, Gd diethylenetriamine pentaacetic acid (Gd-DTPA), dimeglumine, and Gd-bismorpholide, and two iodinated contrast agents, diatrizoate meglumine and iohexol, were incubated with histamine-containing canine mastocytoma cells. Release of histamine into the supernatant was determined at various contrast-medium concentrations after incubation at 37°C for 30 minutes. RESULTS.Iodinated and Gd-based contrast agents caused release of histamine from mastocytoma cells at similar concentrations (50–150 mM). Mannitol, an osmotic stimulus, caused release of histamine only at concentrations greater than 1,000 mM. CONCLUSIONS.Histamine release from canine mastocytoma cells does not appear to be solely due to osmotic effects, but results from direct stimulation by contrast media. For all agents examined, the concentration at which in vitro histamine release occurs far exceeds the serum contrast media concentration expected in routine clinical application. Direct release of histamine from mast cells does not completely explain the pathogenesis of idiosyncratic anaphylactoid responses to contrast media.

COMPARISON OF VASCULAR OPACIFICATION AFTER BOLUS INJECTION OF IODIXANOL-320 AND IOHEXOL-350

RATIONALE AND OBJECTIVES The vascular opacification characteristics of a new nonionic, dimeric contrast agent, iodixanol, have been compared with a nonionic, monomeric agent, iohexol, using ultrafast computed tomography (UFCT). METHODS In 10 experiments with mongrel dogs, the contrast agents were alternately injected into the animals left atrium, and UFCT images were obtained at four cross-sectional levels through the carotid arteries. Time-density curves were then obtained for each carotid artery and each agent. The peak height and area under the curves were compared for each agent. RESULTS Iohexol provided significantly (P < or = .05) greater opacification, determined by paired Students t tests. CONCLUSION This result was predicted from the greater iodine concentration of iohexol (350 mg/mL) compared with iodixanol (320 mg/mL); the difference was greater than expected based on iodine content alone.

Linkage Analysis of von Recklinghausen Neurofibromatosis to DNA Markers on Chromosome 17

Several recent studies indicate that the von Recklinghausen neurofibromatosis (NF1) gene is located near the centromere of chromosome 17 in some families. However, variable expressivity and a very high mutation rate suggest that defects at several different loci could result in phenotypes categorized as NF1. In order to assess this possibility and to map the NF1 gene more precisely, we have used two polymorphic DNA markers from chromosome 17 to screen several pedigrees for linkage to NF1. We ascertained a large Caucasian pedigree (33 individuals sampled, 17 NF1 affected) as well as eight smaller pedigrees and nuclear families (50 individuals sampled, 30 NF1 affected). Here, we report strong evidence of linkage of NF1 to the centromeric marker D17Z1 (maximum lod = 4.42) and a weaker suggestion of linkage to the ERBA1 oncogene (maximum lod = 0.57), both at a recombination fraction of zero. Since obligate cross-overs with NF1 were not observed for either marker in any of the informative families tested, the possibility of NF1 locus heterogeneity is not supported.

Herpes simplex virus encephalitis complicating myxedema coma treated with corticosteroids

Herpes simplex encephalitis (HSE) may develop after high-dose corticosteroids, but has not been described after myxedema coma. We report a patient with myxedema coma who, after initial improvement, developed HSE likely due to activation of dormant herpes simplex virus (HSV) from a combination of myxedema, corticosteroid treatment, and acute illness. MRI of HSE and myxedema showed diffuse diffusion-weighted imaging abnormalities. Neighbors found an 81-year-old man unresponsive in his unheated home. His respiratory rate was irregular at 32, and his pulse was 10 to 20. Paramedics intubated him in the field. His admission temperature was 23 °C; he was slowly warmed and hydrated. Third-degree heart block necessitated transcutaneous pacing. His paced blood pressure was 90 mm Hg systolic. He had nonpitting edema around his orbits and extremities, yellow-tinged sclerae, difficult to auscultate cardiac tones, and course lung sounds. Pressure ulcerations marked his skin. He did not respond to command or question, his eyes remained closed, and he failed to localize pain. He had reactive pupils, poor extraocular movements, minimal …