Hematologic and Inflammatory Predictors of Outcome in Patients with Brain Arteriovenous Malformations.

OBJECTIVE: This study investigated the prognostic value of admission blood counts for arteriovenous malformation (AVM) outcomes and compared admission blood counts for patients with ruptured and unruptured AVMs. METHODS: A retrospective analysis of patients who underwent surgical treatment for a ruptured cerebral AVM between February 1, 2014, and March 31, 2020, was conducted. The primary outcome was poor neurologic outcome, defined as a modified Rankin Scale score ≥2 in patients with unruptured AVMs or >2 in patients with ruptured AVMs. RESULTS: Of 235 included patients, 80 (34%) had ruptured AVMs. At admission, patients with ruptured AVMs had a significantly lower mean (SD) hemoglobin level (12.78 [2.07] g/dL vs. 13.71 [1.60] g/dL, P < 0.001), hematocrit (38.1% [5.9%] vs. 40.7% [4.6%], P < 0.001), lymphocyte count (16% [11%] vs. 26% [10%], P < 0.001), and absolute lymphocyte count (1.41 [0.72] × 103/µL vs. 1.79 [0.68] × 103/µL, P < 0.001), and they had a significantly higher mean (SD) white blood cell count (10.4 [3.8] × 103/µL vs. 7.6 [2.3] × 103/µL, P < 0.001), absolute neutrophil count (7.8 [3.8] × 103/µL vs. 5.0 [2.5] × 103/µL, P < 0.001), and neutrophil count (74% [14%] vs. 64% [13%], P < 0.001). Among patients with unruptured AVMs, white blood cell count ≥6.4 × 103/µL and absolute neutrophil count ≥3.4 × 103/µL were associated with a favorable neurologic outcome, whereas hemoglobin level ≥13.4 g/dL was associated with an unfavorable outcome. Among patients with ruptured AVMs, hypertension was associated with a 3-fold increase in odds of a poor neurologic outcome. CONCLUSIONS: Patients with ruptured and unruptured AVMs present with characteristic profiles of hematologic and inflammatory parameters evident in their admission blood work.

Prognostic Significance of Homocysteine Level on Neurological Outcome in Brain Arteriovenous Malformations.

OBJECTIVE: We aimed to investigate the serum homocysteine (Hcy) level in patients with brain arteriovenous malformation (bAVM) and their impact on neurological outcome during hospitalization. METHOD: We retrospectively reviewed patients diagnosed with bAVMs in Beijing Tiantan Hospital from January 2019 to August 2020. Patients were divided into two groups according to the mRS (modified Rankin Scale) score at discharge. Clinical and laboratory characteristics were compared. Logistic regression analyses were performed to identify the potential risk factors for short-term neurological outcome. RESULTS: A total of 175 bAVM patients were enrolled in the study, including 139 patients with favorable outcome (mRS ≤ 2) and 36 patients with unfavorable outcome (mRS > 2). Hyperhomocysteinemia was identified in 32.6% of cases (n = 57). Serum Hcy level was related to seizure manifestation (P = 0.034) and short-term neurological outcome (P = 0.027). Logistic regression analysis showed that serum glucose (OR 1.897, 95% CI 1.115-3.229; P = 0.018) and Hcy level (OR 0.838, 95% CI 0.720-0.976; P = 0.023) were significantly associated with short-term disability. CONCLUSION: Our results indicated that the lower serum Hcy level is strongly associated with in-hospital unfavorable outcome. Further prospective studies of Hcy natural history and managements in bAVMs are required, which would be valuable for evaluating the disease-modifying efficacy of oral nutritional supplements in bAVM patients.

Secondary S100B Protein Increase Following Brain Arteriovenous Malformation Rupture is Associated with Cerebral Infarction.

Early S100B protein serum elevation is associated with poor prognosis in patients with ruptured brain arteriovenous malformations (BAVM). The purpose of this study is to determine whether a secondary elevation of S100B is associated with early complications or poor outcome in this population. This is a retrospective study of patients admitted for BAVM rupture. A secondary increase of S100B was defined as an absolute increase by 0.1 µg/L within 30 days of admission. Fisher's and unpaired t tests followed by multivariate analysis were performed to identify markers associated with this increase. Two hundred and twenty-one ruptures met inclusion criteria. Secondary S100B protein serum elevation was found in 17.1% of ruptures and was associated with secondary infarction (p < 0.001), vasospasm-related infarction (p < 0.001), intensive care (p = 0.009), and hospital length of stay (p = 0.005), but not with early rebleeding (p = 0.07) or in-hospital mortality (p = 0.99). Secondary infarction was the only independent predictor of secondary increase of S100B (OR 9.9; 95% CI (3-35); p < 0.001). Secondary elevation of S100B protein serum levels is associated with secondary infarction in ruptured brain arteriovenous malformations.

S100B Serum Elevation Predicts In-Hospital Mortality After Brain Arteriovenous Malformation Rupture.

Background and Purpose- S100B protein serum elevation has been associated with poor prognosis in neurologically ill patients. The purpose of this study is to determine whether elevation of S100B is associated with increased in-hospital mortality after brain arteriovenous malformation rupture. Methods- This is a retrospective study of patients admitted for brain arteriovenous malformation rupture. The study population was divided into derivation and validation cohorts. Univariate followed by multivariate logistic regression was used to determine whether elevation of S100B serum levels above 0.5 µg/L during the first 48 hours after admission (S100Bmax48) was associated with in-hospital mortality. Results- Two hundred and three ruptures met inclusion criteria. Twenty-three led to in-hospital mortality (11%). Mean S100Bmax48 was 0.49±0.62 µg/L. In the derivation cohort (n=101 ruptures), multivariate analysis found Glasgow coma scale score ≤8 (odds ratio, 21; 95% CI, 2-216; 0.001) and an S100Bmax48>0.5 µg/L (odds ratio, 19; 95% CI, 2-188; P=0.001) to be associated with in-hospital mortality. When applied to the validation cohort (n=102 ruptures), the same model found only S100Bmax48>0.5 µg/L (odds ratio, 8; 95% CI, 1.5-44; P=0.01) to be associated with in-hospital mortality. Conclusions- Elevated S100B protein serum level is strongly associated with in-hospital mortality after brain arteriovenous malformation rupture.

Radiosurgery reduces plasma levels of angiogenic factors in brain arteriovenous malformation patients.

PURPOSE: Aberrant expression of angiogenic factors has been anecdotally documented in brain arteriovenous malformation (AVM) nidus vessels; however, no data is available on the effect of radiosurgery on the levels of angiogenic factors in AVM patients. We sought to determine the plasma contents of VEGF, TGF-ß, Ang-2 and bFGF in 28 brain AVM patients at baseline and post radiosurgery and further analyzed the relationship between plasma contents of these angiogenic factors with clinicopathologic variables of these patients. METHODS: We enrolled brain AVM patients who underwent Cyberknife radiosurgery at our hospital between January 2014 and December 2015. Brain AVM was confirmed by cerebral angiography and radiosurgery was performed with Cyberknife irradiation. Plasma contents of VEGF, TGF-ß, Ang-2 and bFGF were analyzed using commercially available enzyme-linked immunoassay (ELISA) kits. RESULTS: The baseline plasma VEGF content was 222.63 pg/mL (range 43.25-431.25 pg/mL). At three months post surgery, there was a significant -34.29% decline in plasma VEGF content versus baseline (P = 0.000). Furthermore, the median baseline plasma VEGF levels were higher in brain AVM with a nidus volume ≥ 10 cm3) than those with a nidus volume < 10 cm3 [median(IQR) 293.5 (186.5,359.25) vs. 202 (59.75, 270.75) pg/mL, P = 0.057]. The baseline plasma TGF-ß content was 556.17 pg/mL (range 44.44-1486.11 pg/mL) and there was a significant -27.47% decline in plasma TGF-ß content at 3 months post radiosurgery versus baseline (P = 0.015). Moreover, the baseline plasma ANG-2 content was 214.27 pg/mL (range 77.14-453.76 pg/mL). There was an immediate and significant -12.47% decline in plasma ANG-2 content post surgery versus baseline (P = 0.002). At three months post surgery, the plasma ANG-2 content still remained significantly depressed versus baseline (P = 0.002). In addition, the baseline plasma bFGF content was 9.17 pg/mL (range 3.67-36.78 pg/mL). No significant difference in plasma bFGF content was observed immediately post surgery and 3 months post surgery versus baseline (P = 0.05). CONCLUSIONS: Radiosurgery for brain AVM patients significantly reduced the plasma levels of angiogenic factors. The plasma angiogenic factors may be candidate markers for aberrant agniogenesis of brain AVM and patient response to radiosurgery.

Deep Sequencing of Small RNAs in Blood of Patients with Brain Arteriovenous Malformations.

BACKGROUND: Deregulation of circulating microRNAs (miRNAs) is always associated with development and progression of human diseases. We aimed to assess whether patients with brain arteriovenous malformations (BAVMs) possess a distinct miRNA signature compared with healthy subjects. METHODS: Three patients with unruptured BAVMs and 3 normal control subjects were recruited as case and control groups. Peripheral blood was collected, and miRNA signature was obtained by next-generation sequencing, followed by comparative, functional, and network analyses. Quantitative reverse transcription polymerase chain reaction was performed to validate expression of specific miRNAs. RESULTS: Deep sequencing detected 246 differentially expressed miRNAs in blood samples of patients with BAVMs compared with normal control subjects. For the top 5 miRNAs, 946 target genes were predicted, and a BAVM-specific miRNA-target gene regulatory network was constructed. Functional annotation suggested that 15 of the predicted miRNA-targeted genes were involved in vascular endothelial growth factor signaling, in which 3 critical miRNAs were involved: miR-7-5p, miR-199a-5p, and miR-200b-3p. CONCLUSIONS: We explored the miRNA expression signature of BAVMs, which will provide an important foundation for future studies on the regulation of miRNAs involved in BAVMs.

Relevance of IL-6 and MMP-9 to cerebral arteriovenous malformation and hemorrhage.

The aim of the present study was to investigate the association of inflammatory cytokines and matrix metalloproteinase-9 (MMP-9) with cerebral arteriovenous malformation (AVM) and hemorrhage. A total of 31 AVM patients were divided into groups according to specimen sources; a ruptured group with 14 patients and an unruptured group with 17 patients. The control group comprised 30 epilepsy patients who underwent temporal lobectomy. Peripheral blood was obtained from the 30 control and all 31 AVM patients preoperatively. Tissue samples were removed from the AVM nidus during surgery or from the temporal lobes of patients undergoing surgical treatment for epilepsy. Enzyme-linked immunosorbent assay (ELISA) was used to measure plasma interleukin (IL)-6 levels. Western blot analysis was used to measure the levels of MMP-9 and transcription factors NF-κB and IκBα in the tissues. Immunofluorescence was used to measure tissue MMP-9 expression in each group. Gelatin zymography revealed the expression of activated MMP-2 and MMP-9 in the tissues. All the specimens were analyzed by routine hematoxylin and eosin (H&E) staining. IL-6 levels in the blood of the ruptured group were significantly higher compared with those of the unruptured and control groups (33.25±4.77 vs. 23.79±1.20, P<0.05; and 33.25±4.77 vs. 15.56±0.97, P<0.0001, respectively). NF-κB expression in the AVM ruptured group was significantly higher compared with that of the control group (5.00±0.12 vs. 2.36±0.33, P<0.05), but not with the unruptured group (5.00±0.12 vs. 2.96±0.69, P >0.05). The expression levels of IκBα in the ruptured and unruptured groups were similar to each other, but significantly less than those in the control group (0.12±0.02 vs. 1.27±0.06, P<0.001; and 0.45±0.15 vs. 1.27±0.06, P<0.01, respectively). MMP-9 protein expression levels in the unruptured group were increased compared with those in the control and ruptured groups (1.21±0.34 vs. 0.35±0.06, P<0.05; and 1.21±0.34 vs. 0.32±0.08, P<0.05, respectively). Gelatin zymography showed that the activity of MMP-9 was significantly higher in the ruptured compared with the unruptured and control groups (0.97±0.08 vs. 0.40±0.09, P<0.01; and 0.97±0.08 vs. 0.30±0.07, P<0.01, respectively). In the ruptured group, active MMP-2 expression levels were significantly higher compared with those in the other two groups (1.36±0.17 vs. 0.55±0.12, P=0.019; 1.36±0.17 vs. 0.36±0.09, P=0.006). The levels of IL-6 in the blood correlated with the tissue levels of activated MMP-9 (r=0.1691, P=0.0240). In conclusion, IL-6 expression levels were increased in the plasma of patients with cerebral AVM and this correlated with the activated MMP-9 levels of AVM tissues. Thus, plasma IL-6 levels are a potential predictor of hemorrhage risk in AVM patients.

Relevance of bleeding pattern on clinical appearance and outcome in patients with hemorrhagic brain arteriovenous malformations.

Although several descriptions of the angioarchitectural features of brain arteriovenous malformations (AVMs) associated with higher hemorrhagic risk have been reported, the prognostic value of the different bleeding patterns still needs to be elucidated. This study evaluated the influence on clinical appearance and outcome of the parenchymal and non-parenchymal (subarachnoid hemorrhage-SAH-and intraventricular hemorrhage-IVH) bleedings associated with ruptured AVMs. Clinical records and neuroradiological examinations of 30 patients with hemorrhagic AVMs were reviewed in order to identify their angioarchitectural features and the associated bleeding pattern. These data along with demographic characteristics and treatment modality were dichotomized and their relationship with clinical status at admission and follow-up was tested. IVH as well as parenchymal hematomas larger than 20 cm(3) appeared associated with a severe clinical status at admission, whereas SAH involving basal cisterns was significantly associated with unfavorable outcome. Age, sex and angioarchitectural features did not show significant association with the severity of the prognosis. However, none of these bleeding patterns appeared as an independent risk factor of poor outcome at multivariate analysis. In conclusion, our data emphasized the possibility that non-parenchymal bleeding may worsen the outcome of patients with hemorrhagic AVMs.

Transsylvian-transinsular approaches to the insula and basal ganglia: operative techniques and results with vascular lesions.

BACKGROUND: Lesions in the insula and basal ganglia can be risky to resect because of their depth and proximity to critical structures, particularly in the dominant hemisphere. Transsylvian approaches shorten the surgical distance to these lesions, preserve perisylvian temporal and frontal cortex, and minimize brain transgression. OBJECTIVE: To report our experience with transsylvian-transinsular approaches to vascular lesions. METHODS: The anterior approach opened the sphenoidal and insular portions of the sylvian fissure and exposed the limen insulae and short gyri, whereas the posterior approach opened the insular and opercular portions of the sylvian fissure and exposed the circular sulcus and long gyri. RESULTS: Forty-one patients with vascular lesions (24 arteriovenous malformations [AVMs] and 17 cavernous malformations) were treated surgically with a transsylvian-transinsular approach. Complete resection was obtained in 87.5% of AVMs and 95% of cavernous malformations. Permanent neurological morbidity related to surgery was observed in 2 AVM patients (5%), with the remaining 39 patients (95%) improved or unchanged postoperatively (modified Rankin Scale scores 0-2 in 83%). There were no new language deficits in patients with dominant hemisphere lesions. CONCLUSION: Transsylvian-transinsular approaches safely expose vascular pathology in or deep to the insula while preserving overlying eloquent cortex in the frontal and temporal lobes. The anterior transsylvian-transinsular approach can be differentiated from the posterior approach based on technical differences in splitting the sylvian fissure and anatomic differences in final exposure. Discriminating patient selection and careful microsurgical technique are essential.

[High expression level of interleukin-6 led to elevated hemorrhagic risk of cerebral arteriovenous malformations].

OBJECTIVE: To explore the mechanistic roles of interleukin-6 (IL-6) and matrix metallopeptidase 9 (MMP-9) in cerebral arteriovenous malformation (AVM). METHODS: A total of 31 AVM patients were admitted into Beijing Tiantan Hospital from October 1, 2010 to October 1, 2011, including 14 ruptured and 17 non-ruptured ones. Tissue samples were obtained from all 31 patients and 30 epileptics undergoing temporal lobectomy. The blood samples were obtained from all 31 patients preoperatively and 30 healthy controls. Western blot was employed to measure transcription factors nuclear factor-κB (NF-κB), IκB and MMP-9 in tissues. And immunofluorescence was performed to measure the tissue expression of MMP-9 in each group. Gelatin zymography was used to detect the tissue expressions of activated MMP-9 and MMP-2. RESULTS: The blood levels of IL-6 in the ruptured group were significantly higher than those in the non-ruptured and control groups (33.2±4.8 vs 23.8±1.2 ng/L, P<0.05; 33.4±4.8 vs 15.6±1.0 ng/L, P<0.01). Protein expression in the non-ruptured group was greater than that in the normal and ruptured groups (1.20±0.35 vs 0.34±0.07; 1.20±0.35 vs 0.31±0.09, unit:molecular weight ratio of MMP-9 and ß-actin), and gelatin zymography showed that the activity of MMP-9 was significantly higher in the ruptured than the non-ruptured and control groups (0.98±0.07 vs 0.40±0.09; 0.98±0.07 vs 0.30±0.07, unit: ratio of MMP-9 and standard). In the ruptured group, active MMP-2 expression was significantly higher than that in the other groups. CONCLUSION: IL-6 may stimulate the transformation of MMP-9 into activated form in ruptured AVM tissues and thus lead to an elevated hemorrhage risk of AVM.

Alterations in systemic complement component 3a and 5a levels in patients with cerebral arteriovenous malformations.

The role of the complement cascade in the pathophysiology of cerebral arteriovenous malformation (AVM) is largely undefined. Complement subcomponents, C3a and C5a, are potent anaphylatoxins and key mediators of immuno-inflammatory response. Complement activation may contribute to the pro-inflammatory state observed in AVM. Thus, we sought to determine the systemic levels of C3a and C5a and their response to treatments in patients with AVM. Blood samples of 18 patients undergoing treatment for unruptured AVM, and from 30 healthy control participants, were obtained at four times: (i) pre-treatment, (ii) 24-hours post-embolization, (iii) 24-hours post-resection, and at 1-month follow-up. Plasma concentrations of C3a and C5a were measured using enzyme-linked immunosorbent assay. The pre-treatment mean plasma C3a level was significantly higher in patients with AVM (1817±168 ng/mL) compared to controls (1126±151 ng/mL). The mean C3a level decreased 24-hours after embolization (1482±170 ng/mL) and remained at statistically similar levels 24-hours after resection (1511±149 ng/mL) and at 1-month follow-up (1535±133 ng/mL). Mean C3a levels at the three time points were higher than control levels.The baseline mean plasma C5a level was significantly elevated in patients with AVM (13.1±2.2 ng/mL) compared to controls (3.9±1.5 ng/mL).Mean C5a level decreasedpost-embolization (8.2±2.3 ng/mL) and remained at similar levels post-resection (8.5±3.0 ng/mL) and at 1-month follow-up (7.7±2.9 ng/mL). Mean C5a levels at the three time points were significantly higher than the control levels. We conclude that systemic C3a and C5a levels in patients with AVM are elevated at baseline, decrease significantly after embolization, and remain at the new baseline levels after surgery and 1-month follow-up.

Systemic expression of matrix metalloproteinase-9 in patients with cerebral arteriovenous malformations.

OBJECTIVE: Increased expression angiogenic factors, such as matrix metalloproteinases (MMPs), are associated with the formation of cerebral arteriovenous malformations (AVMs). The objective of this study was to determine plasma levels of MMP-9 of patients with AVMs. METHODS: Blood samples were drawn from 15 patients with AVMs before treatment, 24 hours postembolization, 24 hours postresection, and 30 days postresection. Blood samples were also obtained from 30 healthy controls. Plasma MMP-9 concentrations were measured via enzyme-linked immunosorbent assay. RESULTS: The mean plasma MMP-9 level in AVM patients at baseline was significantly higher than in control patients: 108.04 +/- 16.11 versus 41.44 +/- 2.44 ng/mL, respectively. The mean plasma MMP-9 level 1 day after embolization increased to 172.35 +/- 53.76 ng/mL, which was not significantly elevated over pretreatment levels. One day after resection, plasma MMP-9 levels increased significantly over pretreatment levels to 230.97 +/- 51.00 ng/mL. Mean plasma MMP-9 concentrations 30 days after resection decreased to 92.8 +/- 18.7 ng/mL, which was not different from pretreatment levels but was still significantly elevated over control levels. MMP-9 levels did not correlate with patient sex, age, presentation, or AVM size. CONCLUSION: Plasma MMP-9 levels are significantly elevated over controls at baseline, increase significantly immediately after surgery, and decrease to pretreatment levels during follow-up.

Resection of arteriovenous malformation in a patient with hemophilia type A.

A 34-year-old man with hemophilia type A presented with a huge intracerebral hematoma (ICH) in the left frontoparietal lobe due to rupture of an arteriovenous malformation (AVM). Angiography demonstrated the AVM in the frontoparietal lobe fed by the anterior cerebral arteries and the middle cerebral arteries, with a vein draining into the superior sagittal sinus. He developed signs of cerebral herniation due to the huge ICH. An emergent operation was performed to reduce intracranial pressure and to stop bleeding from the AVM under continuous administration of factor VIII. To prevent postoperative hemorrhage, aggressive blood pressure control and continuous administration of factor VIII were performed for 10 days. His neurological status improved so that he could hold a simple conversation. Continuous administration of factor VIII during surgery and intensive intra- and postoperative therapy resulted in a favorable outcome for this patient with hemophilia type A.

Vascular endothelial growth factor plasma levels are significantly elevated in patients with cerebral arteriovenous malformations.

BACKGROUND: Since growth and de novo generation of cerebrovascular malformations were demonstrated, a strictly congenital model cannot be further supported as unique factor in the pathogenesis of cerebral arteriovenous malformations (AVMs). Vascular endothelial growth factor (VEGF) has previously been demonstrated to be highly expressed in AVMs by immunohistochemical methods. However, systemic VEGF levels have not been analysed previously. This study aimed to investigate VEGF plasma concentrations as a possible plasma marker for neovascularization in patients with cerebral AVMs compared to healthy controls. METHODS: The study included 17 patients with cerebral AVMs and 40 healthy controls. VEGF plasma concentrations were measured by a specific enzyme immuno-assay. RESULTS: VEGF plasma concentrations were significantly higher in patients with cerebral AVMs (mean 140.9 pg/ml, SD 148.5 pg/ml and median 63.0 pg/ml) compared to a healthy control group (mean 44.7 pg/ml, SD 36.4 pg/ml and median 35.0 pg/ml), p = 0.0003. CONCLUSIONS: Our findings suggest that VEGF plasma concentrations might play a role in the pathogenesis of cerebral AVMs. Further studies are necessary and would contribute to an improved understanding of the pathogenesis of cerebral AVMs.

The role of chronic alcohol intake in patients with spontaneous intracranial hemorrhage: a carbohydrate-deficient transferrin study.

BACKGROUND AND PURPOSE: Chronic alcohol intake is considered to be a risk factor for spontaneous intracranial hemorrhage (SICH). However, there is a lack of objective data in this field. The aim was to assess its role in hemorrhagic stroke objectively and to evaluate its correlation with the elevation of gamma-glutamyltransferase (GGT) plasma levels. The reliability of patients' anamnestic data concerning alcohol intake was also assessed. METHODS: Laboratory assessment of the plasma carbohydrate-deficient transferrin (CDT) level was performed in 105 SICH patients and in a control group of 105 patients with dorsalgia. All patients were treated at the Clinic of Neurology, Faculty Hospital, Olomouc, Czech Republic. GGT plasma level values and anamnestic data concerning alcohol consumption were also analyzed. chi(2) tests were applied when assessing statistical significance. RESULTS: The CDT test was positive in 25.7% of SICH patients versus 7.6% of control group subjects (p = 0.0008). GGT plasma levels were elevated in 44.4% of SICH patients with a positive CDT test versus 25.6% of patients with a negative one. The GGT test is not reliable in the detection of alcohol intake when compared with the CDT test (p = 0.71). Only 13.0% of SICH patients with a positive CDT test (subgroup 1) stated regular and high consumption of all types of alcoholic beverages. Another 26.1% of these patients stated regular daily consumption of more than 1 liter, and 47.8% of them stated less than 1 liter of beer, with uncertain data concerning wine and spirits intake. Thirteen percent of subgroup 1 patients denied alcohol consumption altogether. CONCLUSIONS: Chronic alcohol consumption is at least one of several risk factors in one fourth of SICH patients in the Olomouc region of the Czech Republic. The CDT test is the most sensitive method to diagnose chronic alcohol consumption, and it is superior to the examination of GGT and the evaluation of patients' anamnestic data.

Distributions of local oxygen saturation and its response to changes of mean arterial blood pressure in the cerebral cortex adjacent to arteriovenous malformations.

BACKGROUND AND PURPOSE: To test the hypothesis that neither "steal" as cortical ischemia caused by reduced perfusion pressure nor "breakthrough" on the grounds of loss of pressure autoregulation exist in brain tissue surrounding arteriovenous malformations (AVMs), we established patterns of cortical oxygen saturation (SO(2)) adjacent to AVMs and its behavior after alterations of mean arterial blood pressure. METHODS: With a microspectrophotometer, SO(2) was scanned in the cortex around AVMs of 44 patients before and after resection and in that of a non-AVM group (n=42) before transsylvian dissection. Autoregulation was evaluated by linear regression analysis after elevation of mean arterial blood pressure (5 microg/min IV noradrenaline). SO(2) values were calculated as medians, percentage of critical values (<25% SO(2)), and coefficients of variance (approximate heterogeneity of SO(2) distributions). All values are given as mean+/-SD. RESULTS: Forty patients with AVM had an uneventful postoperative course (group A). Four hyperemic complications ("breakthrough") occurred (group B). Autoregulation was tested intact in all groups at all times. Preoperative SO(2) distributions in groups A and C (non-AVMs) were identical. In group B, significantly (P<0.05) lower medians (group A, 52.9+/-16.3%; group B, 44.2+/-17.1%; group C, 51.9+/-11.5% SO(2)), more critical values (group A, 6.5+/-5.1%; group B, 14.7+/-11.1%; group C, 7.1+/-4.9%), and heterogeneous SO(2) distributions (group A, 20.2+/-12.7%; group B, 27.9+/-12.4%; group C, 26.8+/-10.9%) were seen. Increase of median values was significantly higher in group B (76.3+/-10.4% SO(2)) than in group A (65.9+/-13.4% SO(2)) after resection. CONCLUSIONS: Severely hypoxic areas are uncommon in the cortex adjacent to AVMs and occur predominantly in patients prone to hyperemic complications. Reduced perfusion pressure is compensated in most cases, and moderate hyperemia prevails after excision. Reperfusion into unprotected capillaries of severely hypoxic cortical areas results in "breakthrough," for which vasoparalysis appears not to be the underlying mechanism.

Comparing a mass-balance algorithm with a Bayesian regression analysis computer program for predicting serum phenytoin concentrations.

The ability of a mass-balance algorithm to predict non-steady-state phenytoin concentrations in neurosurgery patients was compared with that of Phenda, a computerized Bayesian regression analysis program. Fifty neurosurgery patients who had had two or more initial phenytoin serum concentrations measured at least 60 hours apart and at least 1 hour after any i.v. doses, with the second concentration being not more than twice and not less than half of the first, and who had had a third or final phenytoin measurement (for use in a prediction analysis) were evaluated. The patients' maximum rates of metabolism were calculated by using the two initial phenytoin concentrations and a mass-balance algorithm, and the third phenytoin concentration was predicted. The patients' demographics and phenytoin dosages and concentrations were entered into Phenda, which was used to predict the third phenytoin concentration. The ability of the two methods to predict the third concentration was evaluated by the method of Sheiner and Beal. Fifty observations from 48 patients were evaluated. The mass-balance algorithm had a positive prediction bias of 2.52 mg/L and a precision error of 5.08 mg/L, compared with 2.30 and 5.30, respectively, for Phenda. The difference in the results between the two methods was not significant. There was no significant difference between the mass-balance algorithm and Phenda in the ability to predict phenytoin concentrations.