Living with a Brain AVM: A Quality of Life Assessment.

BACKGROUND AND PURPOSE: Brain arteriovenous malformations (AVM) are uncommon vascular lesions with the risk of hemorrhage, epileptic seizures, neurological deficits, and headache. Comparing the risks of the natural history and that of preventive treatment, a recent study has found observation more beneficial than treatment for unruptured AVMs. This study, however, did not consider the long-term impact of carrying a brain AVM on everyday activities. In this study we analyzed the Quality Of Life (QOL) of patients with untreated AVMs, a measure increasingly used in clinical trials to asses this kind of impact. METHODS: We enrolled 36 patients with unruptured, untreated brain AVM from our hospital database and measured their QOL retrospectively using the EQ-5D-5L questionnaire. As a control group we used the results of the Research Report, a nationwide study based on the quality of life of 5534 healthy Hungarians in 2002. Due to the low number of cases, statistical analysis could not be made. RESULTS: Headache proved to be the most common AVM-related sign in our cohort (40%, n = 17), with a female predominance; neurological deficit was detected in 33% (n = 14), while epileptic seizures occurred in 26% (n = 11), more commonly affecting male subjects. Anxiety and discomfort seemed to be the most prevalent influencing factors on QOL, especially in the youngest age group (18-34 years). Female subjects showed a greater dependence than men in all age groups, though males had a more significant impairment in their usual activities. Older patients were affected more significantly in their self-care and usual activities compared with the younger population. CONCLUSIONS: Untreated AVMs have a significant negative impact on patients carrying unruptured brain AVMs, as proved by QOL assessment. Beside neurological deficits, this impact should also be considered in the therapeutic decision.

Predictors of Surgical Site Infection After Nonemergent Craniotomy: A Nationwide Readmission Database Analysis.

OBJECTIVE: Surgical site infections (SSIs) carry significant patient morbidity and mortality and are a major source of readmissions after craniotomy. Because of their deleterious effects on health care outcomes and costs, identifying modifiable risk factors holds tremendous value. However, because SSIs after craniotomy are rare and most existing data comprise single-institution studies with small sample sizes, many are likely underpowered to discern for such factors. The objective of this study was to use a large hetereogenous patient sample to determine SSI incidence after nonemergent craniotomy and identify factors associated with readmission and subsequent need for wound washout. METHODS: We used the 2010-2014 Nationwide Readmissions Database cohorts to discern for factors predictive of SSI and washout. RESULTS: We identified 93,920 nonemergent craniotomies. There were 2079 cases of SSI (2.2%) and 835 reoperations for washout (0.89%) within 30 days of index admission and there were 2761 cases of SSI (3.6%) and 1220 reoperations for washout (1.58%) within 90 days. Several factors were predictive of SSI in multivariate analysis, including tumor operations, external ventricular drain (EVD), age, length of stay, diabetes, discharge to an intermediate-care facility, insurance type, and hospital bed size. Many of these factors were similarly implicated in reoperation for washout. CONCLUSIONS: SSI incidence in neurosurgery is low and most readmissions occur within 30 days. Several factors predicted SSI after craniotomy, including operations for tumor, younger age, hospitalization length, diabetes, discharge to institutional care, larger hospital bed size, Medicaid insurance, and presence of an EVD. Diabetes and EVD placement may represent modifiable factors that could be explored in subsequent prospective studies for their associations with cranial SSIs.

Multicenter assessment of morbidity associated with cerebral arteriovenous malformation hemorrhages.

BACKGROUND: The optimal management strategy for unruptured cerebral arteriovenous malformations (AVMs) is controversial since the ARUBA trial (A Randomized trial of Unruptured Brain AVMs). An accurate understanding of the morbidity associated with AVM hemorrhages may help clinicians to formulate the best treatment strategy for unruptured AVMs. OBJECTIVE: To determine the morbidity associated with initial cerebral AVM rupture in patients presenting to tertiary medical centers. METHODS: Retrospective chart reviews from three tertiary academic medical centers were performed for the period between 2008 and 2014. All patients admitted with intracranial hemorrhage due to untreated AVMs were included in this study. Patient-specific variables, including demographics, imaging characteristics, neurologic examination results, and clinical outcome, were analyzed and recorded. RESULTS: 101 Patients met the inclusion criteria. Admission National Institutes of Health Stroke Scale (NIHSS) scores were 0, 1-9, and ≥10 in 26%, 29%, and 45% of patients, respectively. Hematoma locations were subarachnoid, intraventricular, intraparenchymal, and combined in 5%, 11%, 32%, and 52% of patients, respectively. Deep venous drainage was present in 43% of AVMs; AVM-associated aneurysms were present in 44% of patients. Emergent hematoma evacuations were performed in 37% of patients and 8% of patients died while in hospital. At discharge, of those who survived, NIHSS scores of ≥1 and ≥10 were found in 69% and 23%, respectively. At the 90-day follow-up, 34% had a modified Rankin Scale (mRS) score >2. Patients with admission NIHSS score ≥10 had significantly higher rates of midline shift, surgical hematoma evacuation, and follow-up mRS ≥3 (p<0.05). CONCLUSIONS: The morbidity associated with cerebral AVM rupture appeared to be higher in our study than previously reported. Morbidity from AVM rupture should be considered as an important factor, together with variables such as risk of AVM rupture and procedural risk, in determining the optimal treatment strategy for unruptured cerebral AVMs.

Toward a comprehensive assessment of functional outcomes in pediatric patients with brain arteriovenous malformations: the Pediatric Quality of Life Inventory.

OBJECTIVE Brain arteriovenous malformations (bAVMs) are rare in pediatric patients but represent the most common cause of hemorrhagic stroke in this population. Pediatric patients demonstrate superior outcomes in comparison with adult patients with similar lesions and presentations. Most studies of clinical outcomes of pediatric bAVMs use the modified Rankin Scale (mRS), despite a lack of validation in pediatric patients. METHODS The authors interviewed the parents of 26 pediatric patients who underwent multimodality bAVM treatment and administered the Pediatric Quality of Life Inventory (PedsQL)-a well-validated tool for pediatric outcomes that quantifies performance in a physical, emotional, social, and school domains. They also reviewed clinical information from the patients' medical charts. Statistical analysis was performed using a log-transformed t-test, the Mann-Whitney exact test, the Kruskal-Wallis test, and Spearman correlation. In addition, the literature was reviewed for prior reports of clinical outcome of pediatric cases of bAVM. RESULTS The average PedsQL health-related quality of life score was 71 ± 24, with an average age at diagnosis of 12.5 years and an average follow-up period of 6.8 years. Seventeen patients (65%) presented with hemorrhage and 4 (15%) with seizures. PedsQL scores correlated strongly and at a statistically significant level (p < 0.001) with mRS, Pediatric Overall Performance Category (POPC), Pediatric Cerebral Performance Category (PCPC), and Glasgow Outcome Scale scores. Multivariate modeling validated special education, corrective devices, and cure status as significant predictors of PedsQL scores. Statistically significant risk factors for undergoing placement of a ventriculoperitoneal shunt included lower Glasgow Coma Scale motor scores on admission (p = 0.042), cerebellar location (p = 0.046), and nidus volume (p = 0.017). Neither treatment modality nor location statistically affected clinical outcomes at follow-up. CONCLUSIONS There have been few studies of long-term clinical outcomes of bAVM in pediatric patients, and previously published studies have used conventional metrics that have been validated in the adult population, such as the mRS. Although these metrics can serve as reasonable surrogates, an accurate understanding of overall health-related quality of life is contingent on utilizing validated toolsets, such as the PedsQL.

Pre-existing, incidental and hemorrhagic AVMs in pregnancy and postpartum: Gestational age, morbidity and mortality, management and risk to the fetus.

OBJECTIVE: The objective of this article is to analyze the maternal and fetal outcomes of pregnancies that present with arteriovenous malformations (AVMs). METHODS: A literature review was performed that analyzed 65 cases of AVM during pregnancy previously reported in English literature. RESULTS: Sixty-five cases of pregnancy-associated AVM were identified. The patients' ages ranged from 16 to 45 years, with a mean of 28 ± 4.9 years. Sixteen cases (24.6%) were pre-existing AVMs. There were 54 cases (83.1%) of AVM ruptured during pregnancy and postpartum: Six cases (11.1%) were in the first trimester, 24 (44.4%) were in the second, 22 (40.7%) were in the third trimester and two (3.7%) were postpartum. Unfavorable maternal clinical outcome (modified Rankin Scale (mRS) ≥ 2) was identified in 20 cases (30.8%) and abortion occurred in 10 cases (15.4%). There were three maternal deaths, yielding a case mortality rate of 4.6%. Fifty-three fetuses were born via cesarean section in 42 cases and vaginal delivery in 10 cases; 48 were in good health, three were temporarily intubated, one was macrosomic and one died. In univariate analysis, AVM hemorrhage presentation was significantly associated with a poor maternal outcome (mRS ≥ 2) (p = 0.030); however, not significantly associated with fetus risk (p = 0.864). Gestational age was not significantly associated with poor maternal outcome (p = 0.875) or fetal risk (p = 0.790). CONCLUSION: AVM hemorrhage presentation was significantly associated with poor maternal outcome. Pre-existing ruptured AVM may not be associated with fetal risk. Gestational age of AVM rupture was not significantly associated with poor maternal outcome or fetal risk.

Critical assessment of the morbidity associated with ruptured cerebral arteriovenous malformations.

BACKGROUND: An accurate understanding of the morbidity and mortality associated with brain arteriovenous malformation (AVM) hemorrhage is important in determining the management of unruptured AVMs. Recent studies suggest this morbidity to be lower than assumed. We sought to perform a detailed critical assessment of the morbidity associated with ruptured brain AVMs. METHODS: A retrospective chart review from a single-center tertiary care medical center was performed. Inclusion criteria were patients admitted with intracranial hemorrhage caused by a previously untreated AVM. Forty variables were analyzed including patient demographics, imaging findings, clinical course, and clinical examinations. RESULTS: From 2008 to 2013, of the 51 patients who fit our inclusion criteria, we found admission National Institutes of Health Stroke Scale (NIHSS) scores of 0, 1-9, and ≥10 in 22%, 24%, and 55%, respectively. Hematoma location was parenchymal in 33%, intraventricular in 10%, subarachnoid in 4%, and combined in 53%. Deep venous drainage was present in 35% of cases and associated aneurysms were present in 37%. 43% underwent emergency hematoma evacuation while four patients died during their admission. Of those who survived, 74% had neurologic deficits upon discharge (NIHSS ≥1), with 25.5% of patients having a severe deficit (NIHSS ≥10). On follow-up, 55% were independent in their daily activities of living. CONCLUSIONS: Our assessment of morbidity associated with brain AVM rupture is higher than previously assumed and reported. These results should be further validated in a larger, more representative sample. An accurate understanding of the morbidity associated with AVM rupture is important as more patients with unruptured brain AVMs seek consultation.

Comparative effectiveness of treatments for cerebral arteriovenous malformations: trends in nationwide outcomes from 2000 to 2009.

OBJECT: The development of multimodality approaches for the treatment of cerebral arteriovenous malformations (AVMs), including microsurgery, endovascular therapy, and radiosurgery, has shifted modern treatment paradigms in the last 10 years. This study examines these changes in detail from a nationwide perspective. METHODS: The authors examined data from 2001 to 2009 in the Nationwide Inpatient Sample (NIS) database, and they assessed the safety, quality, and cost-effectiveness, including the total number of discharges, discharge proportion, length of stay, and hospital charges. The authors also examined patient demographics (including age, sex, income level, and insurance), hemorrhage status at presentation, and trends in open surgical and endovascular treatment. RESULTS: A total of 33,997 inpatient admissions for patients with a primary diagnosis of intracranial AVM were identified, with a mean of 4191 patients admitted annually. The mean hospital charges increased 2-fold over the study period without significant differences in outcomes. There were substantial differences between surgical, endovascular, radiosurgical, and multimodality treatments. The proportion of AVMs treated microsurgically remained stable over this period, while the proportion treated endovascularly dramatically increased in size, and the data demonstrate important patient-level distinctions among groups. Outcomes and complication profiles were significantly different between treatment modalities and were impacted by age and hemorrhage status. CONCLUSIONS: Charges associated with treatment of cerebral AVMs to the payer and society have increased dramatically over the first decade of the 21st century without clear improvements in quality parameters. However, analysis of the 3 primary treatment modalities has demonstrated differences and warrants further investigation to understand which patient population would benefit maximally from each. Unfortunately, with only imprecise measurements of quality in health care delivery, it remains imperative to develop national databases in which parameters, such as survival, functional outcomes, quality of life, and complication rates, can be assessed to examine the value of care delivered in a more meaningful way. Demonstrating an ever-increasing value of delivered health care will be imperative in our evolving health care system.

Brain arteriovenous malformation multiplicity predicts the diagnosis of hereditary hemorrhagic telangiectasia: quantitative assessment.

BACKGROUND AND PURPOSE: The purpose of this study was to quantitatively estimate the relationship between multiplicity of brain arteriovenous malformations (bAVMs) and the diagnosis of hereditary hemorrhagic telangiectasia (HHT). METHODS: We combined databases from 2 large North American bAVM referral centers, including demographics, clinical presentation, and angiographic characteristics, and compared patients with HHT with non-HHT patients. Logistic regression analysis was performed to quantify the association between bAVM multiplicity and odds of HHT diagnosis. Sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratios were calculated to determine accuracy of bAVM multiplicity for screening HHT. RESULTS: Prevalence of HHT was 2.8% in the combined group. bAVM multiplicity was present in 39% of patients with HHT and was highly associated with diagnosis of HHT in univariate (OR, 83; 95% CI, 40-173; P<0.0001) and multivariable (OR, 86; 95% CI, 38-195; P<0.001) models adjusting for age at presentation (P=0.013), symptomatic presentation (P=0.029), and cohort site (P=0.021). bAVM multiplicity alone was associated with high specificity (99.2%; 95% CI, 98.7%-99.6%) and negative predictive value (98.3%; 95% CI, 97.6%-98.8%) and low sensitivity (39.3%; 95% CI, 26.5%-53.2%) and positive predictive value (59.5%; 95% CI, 42.1%-75.2%). Positive and negative likelihood ratio was 51 and 0.61, respectively, for diagnosis of HHT. HHT bAVMs were also more often smaller in size (<3 cm), noneloquent in location, and associated with superficial venous drainage compared with non-HHT bAVMs. CONCLUSIONS: Multiplicity of bAVMs is highly predictive of the diagnosis of HHT. The presence of multiple bAVMs should alert the clinician to the high probability of HHT and lead to comprehensive investigation for this diagnosis.

Economic burden of intracranial vascular malformations in adults: prospective population-based study.

BACKGROUND AND PURPOSE: Although intracranial vascular malformations (IVMs) are the leading cause of intracerebral hemorrhage (ICH) in young adults, there has not been a cost-of-illness study on an unselected cohort. METHODS: We measured the direct healthcare costs (inpatient, outpatient, intervention, and brain imaging) incurred by every adult within 3 years after their first presentation with a brain arteriovenous malformation (AVM) or cavernous malformation (CM) in a prospective, population-based study. We estimated the indirect cost of lost productivity for the whole cohort over the same period by projecting questionnaire responses from living consenting adults. RESULTS: 369 adults (AVM=229 [62%], CM=140 [38%]) incurred healthcare costs of pound 5.96 million over 3 years, of which AVMs accounted for 90%, inpatient care accounted for 75%, and the first year of care accounted for 69%. Median 3-year healthcare costs were statistically significantly higher for adults presenting with ICH, aged <65 years, receiving interventional treatment, and adults with AVMs rather than CMs ( pound 15,784 versus pound 1385, P<0.0005). Healthcare costs diminished with increasing AVM nidus size (P=0.005). Mean 3-year costs of lost productivity per questionnaire respondent (n=145) were pound 17,111 for AVMs and pound 6752 for CMs (P=0.1), and the projected 3-year cost of lost productivity for all 369 adults was pound 8.7 million. CONCLUSIONS: The costs of healthcare and lost productivity attributable to IVMs are considerable, and highest in those aged <65 years, presenting with ICH, receiving interventional treatment, and harboring AVMs rather than CMs. Long-term studies of the cost-effectiveness of interventional treatment are needed.

Population stratification in a case-control study of brain arteriovenous malformation in Latinos.

BACKGROUND: Genetic association studies conducted in admixed populations may be confounded by population stratification resulting in spurious associations. The purpose of this pilot study was to determine the presence and effect of population stratification in a case-control study of brain arteriovenous malformation (BAVM). METHODS: We tested 83 ancestry informative markers in BAVM cases and healthy controls of self-reported Latino race/ethnicity (n = 294). Individual ancestry estimates (IAE) were obtained using the Structure program, assuming 3 underlying subpopulations. Summary chi(2) tests comparing genotype frequency of ancestry informative markers were used to detect stratification and IAE were included as covariates in logistic regression analysis to account for differences in genetic background. RESULTS: Admixture estimates for Latinos (overall 47% native American, 45% European and 8% African ancestry) revealed heterogeneity between individuals within ancestral groups. The summary chi(2) test was significant (p = 0.005), suggesting ancestral differences between cases and controls. Furthermore, genetic ancestry was associated with frequency differences in a promoter variant in the IL-6 gene (IL-6 -174G>C). On average, subjects with the IL6 -174 GG genotype had 6% greater Native American ancestry (p = 0.023). Age- and sex-adjusted risk of BAVM associated with the IL-6 -174 GG genotype was 1.85 (95% CI 0.99-3.48, p = 0.055), and further adjustments for IAE yielded an OR of 1.96 (95% CI 1.03-3.72, p = 0.039). CONCLUSION: The IL-6 -174G>C polymorphism was associated with increased risk of BAVM among Latinos after accounting for differences in ancestral background. These results suggest subtle, negative confounding and illustrate the importance of addressing population stratification in case-control studies conducted in admixed populations.

Malformações arteriovenosas encefálicas: aspectos morfológicos, clínicos e operatórios. Revisão da literatura / Intracranial arteriovenous malformation. A literature review

É feita revisão da literatura sobre malformações arteriovenosas(MAV)encefálicas. MAV são anomalias morfológicas neurovasculares caracterizadas por comunicação direta entre artérias e veias , sem interposição do leito capilar, portanto sem resistência ao fluxo sanguíneo. Morfologicamente, MAV possuem três componentes distintos:aferências, nidus e eferências.As aferências incluem vasos originados de quaisquer artérias intra ou extracranianas que nutrem as MAV.O nidus corresponde a um enovelado complexo de artérias e veias anormais,unidas por uma ou mais fístulas além de calcificações e aneurismas intranidais. As eferências constituem as drenagens venosas, que podem ser superficial,profunda ou mista.Acidentes vasculares encefálicos(AVE)hemorrágicos são as manifestações mais comuns,ocorrendo em aproximadamente 50 por cento dos casos.O tratamento de MAV pode ser microcirurgia,embolização endovascular,radiocirúrgico estereotáxico,conservador ou multidisciplinar.Ressecção cirúrgica completa de MAV é considerada a melhor opção de tratamento,eliminando risco de futura hemorragia.Apesar do desenvolvimento tecnológico na área de neurocirurgia endovascular nas últimas décadas, a fisiopatologia de MAV e sua história natural ainda não estão bem esclarecidas.O tratamento representa um grande desafio.Acreditamos que estudos sobre complexidade arquitetônica e hemodinâmica de MAV são necessários a fim de estabelecer fatores de risco e prognósticos,melhorando os resultados do tratamento.

Inter- and intraobserver variability in the assessment of brain arteriovenous malformation angioarchitecture and endovascular treatment results.

BACKGROUND AND PURPOSE: Several angiographic features of brain arteriovenous malformations (BAVMs) have been associated with an increased risk of hemorrhage. However, interpretation of these features may not be consistent between observers. We conducted a study to determine inter- and intraobserver agreement of various angioarchitectural characteristics of BAVM. MATERIALS AND METHODS: Two experienced interventional neuroradiologists independently reviewed pre- and post-endovascular treatment angiograms from 50 consecutive patients. Axial CT and/or MR images before treatment were included. We collected the following data: Spetzler-Martin grades, number of involved arterial territories, associated aneurysms by location (circle of Willis, feeding artery, intranidal, and venous), and nidus reduction after endovascular treatment (<33%, 33%-66%, and >66%). The reviewers were compared with each other, and 1 was compared with himself after a 3-month interval. Measures of agreement were performed by using the kappa statistic (kappa) for nominal data and the weighted kappa for ordinal data. RESULTS: Inter- and intraobserver agreement were higher for assessment of the Spetzler-Martin grade (weighted kappa = 0.70/0.75) and nidus size reduction after endovascular treatment (kappa = 0.74/0.77). Inter- and intraobserver agreement were inferior for findings concerning feeding artery aneurysms (kappa = 0.19/0.36), intranidal aneurysms (kappa = 0.34/0.35), and venous aneurysms (kappa = 0.50/0.67). CONCLUSION: Angiographic characteristics of BAVMs considered as risk factors for hemorrhage, such as aneurysms, are not reliably detected on global angiograms between different observers. In contrast, the Spetzler-Martin grading system and angiographic results of endovascular treatment can be used with high observer agreement.

[Postoperative morbidity and mortality after microsurgical exclusion of cerebral arteriovenous malformations. Current data and analysis of recent literature]. / Morbidité et mortalité du traitement chirurgical des malformations artério-veineuses cérébrales. Données actuelles et analyse de la littérature récente.

BACKGROUND AND PURPOSE: Microsurgical exclusion of a cerebral arteriovenous malformation (AVM) can compare favorably with radiosurgery. We sought to assess its rate of morbidity-mortality as it is presently reported in the literature, and to discuss some of its current and worthwhile indications. METHODS: Through Medline and additional searches by hand, we retrieved studies reporting the clinical and angiographic results after microsurgical excision of an AVM published between january 1990 and december 2000. RESULTS: a) Postoperative mortality was 3.3% (68/2 452 patients from 25 studies). Permanent postoperative morbidity was 8.6%. Morbidity was never absent varying from 1.5% to 18,7%. The morbidity-mortality rate increased with an increasing Spetzler-Martin's grade, and was related to the location of the AVM. A 4.6% morbidity (from 1.5% to 9.7%) and a zero mortality were reported after microsurgical removal of small lesions of less than 3 cm in diameter. b) Postoperative angiography confirmed a total excision of the AVM in 97% of the cases (1 050/1 076 patients over 11 series), varying from 91% to 100%. c) Permanent morbidity related to pre-surgical embolization varied from 4% to 8.9%. Results from multiple or combined treatment including microsurgery could not be summed up. CONCLUSIONS: A complete and definitive microsurgical excision of an AVM can be achieved with a high success rate and a low morbidity-mortality rate, according to sound indications and to the neurosurgeon's personal experience. The choice for a best treatment of an AVM is no longer limited to microsurgery; it is a team decision where the neurosurgeon plays a determining role.