Background Approximately 10% of hereditary hemorrhagic telangiectasia (HHT) patients harbour brain vascular malformations (VMs). Intracranial hemorrhage (ICH) from brain VMs can lead to death or morbidity, while treatment options for brain VMs also have associated morbidity. The modified Rankin Scale (mRS) may provide an approach to identifying HHT-brain VM patients with poor outcomes, and their predictors. We aimed to measure the relationship between mRS score and brain VM, brain VM number, as well as other aspects of HHT, at enrollment and during prospective follow-up. Methods 1637 HHT patients (342 with brain VMs) were recruited from 14 HHT centres of the Brain Vascular Malformation Consortium since 2010 and followed prospectively (mean = 3.4 years). We tested whether the presence of brain VM, other HHT organ involvement, and HHT mutation genotype were associated with worse mRS scores at baseline and during follow-up, using linear mixed models, adjusting for age, sex, and year of visit. Results Presence of brain VMs was not associated with worse mRS score at baseline and there was no significant worsening of mRS with prospective follow-up in these patients; 92% had baseline mRS of 0–2. HHT-related gastrointestinal (GI) bleeding was associated with worse mRS scores at baseline (0.37, 95% CI 0.26–0.47, p < 0.001), as were history of anemia (0.35, 95% CI 0.27–0.43, p < 0.001) and liver VMs (0.19, 95% CI 0.09–0.30, p < 0.001). Presence of pulmonary arteriovenous malformations (AVMs) was not associated with worse mRS scores at baseline. mRS score was not associated with either HHT genotype ( Endoglin vs ACVRL1 ). Only GI bleeding was associated with a significantly worsening mRS during prospective follow-up (0.64, 95% CI 0.21–1.08, p = 0.004). Conclusion Most HHT-brain VM patients had good functional capacity (mRS scores 0–2) at baseline that did not change significantly over 3.4 mean years of follow-up, suggesting that mRS may not be useful for predicting or measuring outcomes in these patients. However, HHT patients with GI bleeding, anemia history or liver VMs had worse mRS scores, suggesting significant impact of these manifestations on functional capacity. Our study demonstrates the insensitivity of the mRS as an outcomes measure in HHT brain VM patients and reinforces the continued need to develop outcomes measures, and their predictors, in this group.

Background Retrospective questionnaire and healthcare administrative data suggest reduced life expectancy in untreated hereditary hemorrhagic telangiectasia (HHT). Prospective data suggests similar mortality, to the general population, in Denmark’s centre-treated HHT patients. However, clinical phenotypes vary widely in HHT, likely affecting mortality. We aimed to measure predictors of mortality among centre-treated HHT patients. HHT patients were recruited at 14 HHT centres of the Brain Vascular Malformation Consortium (BVMC) since 2010 and followed annually. Vital status, organ vascular malformations (VMs) and clinical symptoms data were collected at baseline and during follow-up (N = 1286). We tested whether organ VMs, HHT symptoms and HHT genes were associated with increased mortality using Cox regression analysis, adjusting for patient age, sex, and smoking status. Results 59 deaths occurred over average follow-up time of 3.4 years (max 8.6 years). A history of anemia was associated with increased mortality (HR = 2.93, 95% CI 1.37–6.26, p = 0.006), as were gastro-intestinal (GI) bleeding (HR = 2.63, 95% CI 1.46–4.74, p = 0.001), and symptomatic liver VMs (HR = 2.10, 95% CI 1.15–3.84, p = 0.015). Brain VMs and pulmonary arteriovenous malformations (AVMs) were not associated with mortality ( p > 0.05). Patients with SMAD4 mutation had significantly higher mortality (HR = 18.36, 95% CI 5.60–60.20, p < 0.001) compared to patients with ACVRL1 or ENG mutation, but this estimate is imprecise given the rarity of SMAD4 patients (n = 33, 4 deaths). Conclusions Chronic GI bleeding, anemia and symptomatic liver VMs are associated with increased mortality in HHT patients, independent of age, and in keeping with the limited treatment options for these aspects of HHT. Conversely, mortality does not appear to be associated with pulmonary AVMs or brain VMs, for which patients are routinely screened and treated preventatively at HHT Centres. This demonstrates the need for development of new therapies to treat chronic anemia, GI bleeding, and symptomatic liver VMs in order to reduce mortality among HHT patients.

BACKGROUND AND PURPOSE: Hemodynamic features of brain AVMs may portend increased hemorrhage risk. Previous studies have suggested that MTT is shorter in ruptured AVMs as assessed on quantitative color-coded parametric DSA. This study assesses the interrater reliability of MTT measurements obtained using quantitative color-coded DSA. MATERIALS AND METHODS: Thirty-five color-coded parametric DSA images of 34 brain AVMs were analyzed by 4 neuroradiologists with experience in interventional neuroradiology. Hemodynamic features assessed included MTT of the AVM and TTP of the dominant feeding artery and draining vein. Agreement among the 4 raters was assessed using the intraclass correlation coefficient. RESULTS: The interrater reliability among the 4 raters was poor (intraclass correlation coefficient = 0.218; 95% CI, 0.062–0.414; P value = .002) as it related to MTT assessment. When the analysis was limited to cases in which the raters selected the same image to analyze and selected the same primary feeding artery and the same primary draining vein, interrater reliability improved to fair (intraclass correlation coefficient  = 0.564; 95% CI, 0.367–0.717; P < .001). CONCLUSIONS: Interrater reliability in deriving color-coded parametric DSA measurements such as MTT is poor so minor differences among raters may result in a large variance in MTT and TTP results, partly due to the sensitivity and 2D nature of the technique. Reliability can be improved by defining a standard projection, feeding artery, and draining vein for analysis.

BACKGROUND AND PURPOSE: Automated CTP software is increasingly used for extended window emergent large-vessel occlusion to quantify core infarct. We aimed to assess whether RAPID software underestimates core infarct in patients with an extended window recently receiving IV iodinated contrast. MATERIALS AND METHODS: We reviewed a prospective, single-center data base of 271 consecutive patients who underwent CTA 6 CTP for acute ischemic stroke from May 2018 through January 2019. Patients with emergent large-vessel occlusion confirmed by CTA in the extended window (.6 hours since last known well) and CTP with RAPID postprocessing were included. Two blinded raters independently assessed CT ASPECTS on NCCT performed at the time of CTP. RAPID software used relative cerebral blood flow of,30% as a surrogate for irreversible core infarct. Patients were dichotomized on the basis of receiving recent IV iodinated contrast (,8hours before CTP) for a separate imaging study. RESULTS: The recent IV contrast and contrast-naive cohorts comprised 23 and 15 patients, respectively. Multivariate linear regression analysis demonstrated that recent IV contrast administration was independently associated with a decrease in the RAPID core infarct estimate (proportional increase = 0.34; 95% CI, 0.12-0.96; P =.04). CONCLUSIONS: Patients who received IV iodinated contrast in proximity (,8 hours) to CTA/CTP as part of a separate imaging study had a much higher likelihood of core infarct underestimation with RAPID compared with contrast-naive patients. Over-reliance on RAPID postprocessing for treatment disposition of patients with extended window emergent large-vessel occlusion should be avoided, particularly with recent IV contrast administration.

With prospective imaging to screen the spinal cord, the authors found SCCMs in 21 of 29 familial CCM1 patients, a prevalence of 72.4%. They conclude that the study demonstrates that SCCMs are indeed a common finding in patients with familial CCM and supports the idea of familial CCM syndrome as a progressive systemic disease that affects the entire central nervous system. They found an expected positive correlation of number of SCCMs with both patient age and number of intracranial CCMs. They also found a high prevalence of vertebral intraosseous vascular malformations (69%), including atypical (T1 hypointense) intraosseous vascular malformation in approximately 38% of the patients who underwent MR imaging screening. BACKGROUND AND PURPOSE: Cavernous malformations occur most often in the brain but can occur in the spinal cord. Small studies of patients with familial cerebral cavernous malformations suggested a prevalence of spinal cord cavernous malformations of 20%–42%. We aimed to review our familial cohort and prospectively estimate the prevalence of spinal cord cavernous malformations. MATERIALS AND METHODS: We initially reviewed our familial cerebral cavernous malformations cohort for spinal cord cavernous malformations and reviewed clinical spine MR imaging examinations for sequence sensitivity. We then prospectively performed research MR imaging of the spinal cord in 29 patients from the familial cohort to estimate the prevalence. RESULTS: Gradient-based sequences identified the most spinal cord cavernous malformations on clinical MR images, forming the basis for developing our screening MR imaging. Screening spinal cord MR imaging demonstrated a prevalence of 72.4%, and a positive correlation with patient age and number of cerebral cavernous malformations. CONCLUSIONS: Spinal cord cavernous malformations occur commonly in the familial cerebral cavernous malformation population. Gradient-based sequences are the most sensitive and should be used when spinal cord cavernous malformations are suspected. This study establishes the prevalence in the familial population at around 70% and supports the idea that this condition is a progressive systemic disease that affects the entire central nervous system.

BACKGROUND AND PURPOSE: Although intracranial dural arteriovenous fistulas are principally supplied by dural branches of the external carotid, internal carotid, and vertebral arteries, they can also be fed by pial arteries that supply the brain. We sought to determine the frequency of neurologic deficits following treatment of intracranial dural arteriovenous fistulas with and without pial artery supply. MATERIALS AND METHODS: One hundred twenty-two consecutive patients who underwent treatment for intracranial dural arteriovenous fistulas at our hospital from 2008 to 2015 were retrospectively reviewed. Patient data were examined for posttreatment neurologic deficits; patients with such deficits were evaluated for imaging evidence of cerebral infarction. Data were analyzed with multivariable logistic regression. RESULTS: Of 122 treated patients, 29 (23.8%) had dural arteriovenous fistulas with pial artery supply and 93 (76.2%) had dural arteriovenous fistulas without pial arterial supply. Of patients with pial artery supply, 4 (13.8%) had posttreatment neurologic deficits, compared with 2 patients (2.2%) without pial artery supply (P = .04). Imaging confirmed that 3 patients with pial artery supply (10.3%) had cerebral infarcts, compared with only 1 patient without pial artery supply (1.1%, P = .03). Increasing patient age was also positively associated with pial supply and treatment-related complications. CONCLUSIONS: Patients with dural arteriovenous fistulas supplied by the pial arteries were more likely to experience posttreatment complications, including ischemic strokes, than patients with no pial artery supply. The approach to dural arteriovenous fistula treatment should be made on a case-by-case basis so that the risk of complications can be minimized.

Fazit Patienten mit AVM-Diagnose ohne Anhalt für ein zerebrales Blutungsereignis werden üblicherweise konservativ geführt. Bei etwa einem Drittel der AVM-Patienten lässt sich jedoch eine vorangegangene okkulte Mikroblutung nachweisen. Diese Patienten lassen sich weder anhand demografischer noch anhand klinischer oder anatomischer Charakteristika, sondern ausschließlich durch den radiologischen oder histologischen Nachweis von Hämosiderinablagerungen bzw. einer Makrophageninfiltration von Patienten mit stabiler, nicht rupturierter AVM unterscheiden. Aufgrund des erhöhten Risikos für eine nachfolgende klinisch manifeste Blutung, so die Empfehlung der Autoren, sollte bei asymptomatischen AVM-Patienten mit radiologisch nachgewiesener asymptomatischer Mikrohämorrhagie kein abwartendes Vorgehen gewählt, sondern eine chirurgische Behandlung eingeleitet werden.

BACKGROUND AND PURPOSE: Intracranial hemorrhage is the most serious outcome for brain arteriovenous malformations. This study examines associations between venous characteristics of these lesions and intracranial hemorrhage. MATERIALS AND METHODS: Statistical analysis was performed on a prospectively maintained data base of brain AVMs evaluated at an academic medical center. DSA, CT, and MR imaging studies were evaluated to classify lesion side, drainage pattern, venous stenosis, number of draining veins, venous ectasia, and venous reflux. Logistic regression analyses were performed to identify the association of these angiographic features with intracranial hemorrhage of any age at initial presentation. RESULTS: Exclusively deep drainage (OR, 3.42; 95% CI, 1.87–6.26; P < .001) and a single draining vein (OR, 1.98; 95% CI, 1.26–3.08; P = .002) were associated with hemorrhage, whereas venous ectasia (OR, 0.52; 95% CI, 0.34–0.78; P = .002) was inversely associated with hemorrhage. CONCLUSIONS: Analysis of venous characteristics of brain AVMs may help determine their prognosis and thereby identify lesions most appropriate for treatment.

BACKGROUND AND PURPOSE: The imaging characteristics and modes of presentation of brain AVMs may vary with patient age. Our aim was to determine whether clinical and angioarchitectural features of brain AVMs differ between children and adults. MATERIALS AND METHODS: A prospectively collected institutional data base of all patients diagnosed with brain AVMs since 2001 was queried. Demographic, clinical, and angioarchitecture information was summarized and analyzed with univariable and multivariable models. RESULTS: Results often differed when age was treated as a continuous variable as opposed to dividing subjects into children (18 years or younger; n = 203) versus adults (older than 18 years; n = 630). Children were more likely to present with AVM hemorrhage than adults (59% versus 41%, P < .001). Although AVMs with a larger nidus presented at younger ages (mean of 26.8 years for >6 cm compared with 37.1 years for <3 cm), this feature was not significantly different between children and adults (P = .069). Exclusively deep venous drainage was more common in younger subjects when age was treated continuously (P = .04) or dichotomized (P < .001). Venous ectasia was more common with increasing age (mean, 39.4 years with ectasia compared with 31.1 years without ectasia) and when adults were compared with children (52% versus 35%, P < .001). Patients with feeding artery aneurysms presented at a later average age (44.1 years) than those without such aneurysms (31.6 years); this observation persisted when comparing children with adults (13% versus 29%, P < .001). CONCLUSIONS: Although children with brain AVMs were more likely to come to clinical attention due to hemorrhage than adults, venous ectasia and feeding artery aneurysms were under-represented in children, suggesting that these particular high-risk features take time to develop.