Jo J. Bhattacharya

Prospective, Population-Based Detection of Intracranial Vascular Malformations in Adults The Scottish Intracranial Vascular Malformation Study (SIVMS)

Background and Purpose— Intracranial vascular malformations (IVMs) are an important cause of intracranial hemorrhage, epilepsy, and long-term disability in adults. There are no published prospective, population-based studies dedicated to the detection of any type of IVM (cavernous malformations, venous malformations, and arteriovenous malformations [AVMs] of the brain or dura). Therefore, we established the Scottish Intracranial Vascular Malformation Study (SIVMS) to monitor detection and long-term prognosis of people with IVMs. Methods— We used multiple overlapping sources of case ascertainment to identify adults (aged ≥16 years) with a first-ever-in-a-lifetime diagnosis of any type of IVM made between January 1, 1999, and December 31, 2000, while resident in Scotland (mid-1999 adult population estimate 4 110 956). Results— Of 418 notifications to SIVMS, 190 adults (45%) were included, 181 (95%) of whom were deemed to harbor a definite IVM after review of diagnostic brain imaging and/or reports of autopsy/surgical excision pathology. The crude detection rate (per 100 000 adults per year) was 2.27 (95% CI, 1.96 to 2.62) for all IVMs, 1.12 (95% CI, 0.90 to 1.37) for brain AVMs, 0.56 (95% CI, 0.41 to 0.75) for cavernous malformations, 0.43 (95% CI, 0.31 to 0.61) for venous malformations, and 0.16 (95% CI, 0.08 to 0.27) for dural AVMs. Conclusions— In addition to providing data on the public health importance and comparative epidemiology of IVMs, continuing recruitment and follow-up of this prospective, population-based cohort will provide estimates of IVM prognosis.

Outcome after interventional or conservative management of unruptured brain arteriovenous malformations: a prospective, population-based cohort study

BACKGROUND The decision about whether to treat an unruptured brain arteriovenous malformation (AVM) depends on a comparison of the estimated lifetime risk of intracranial haemorrhage with the risks of interventional treatment. We aimed to test whether outcome differs between adults who had interventional AVM treatment and those who did not. METHODS All adults in Scotland who were first diagnosed with an unruptured AVM during 1999-2003 (n=114) entered our prospective, population-based study. We compared the baseline characteristics and 3-year outcome of adults who received interventional treatment for their AVM (n=63) with those who did not (n=51). FINDINGS At presentation, adults who were treated were younger (mean 40 vs 55 years of age, 95% CI for difference 9-20; p<0.0001), more likely to present with a seizure (odds ratio 2.4, 95% CI 1.1-5.0), and had fewer comorbidities (median 3 vs 4, p=0.03) than those who were not treated. Despite these baseline imbalances, treated and untreated groups did not differ in progression to Oxford Handicap Scale (OHS) scores of 2-6 (log-rank p=0.12) or 3-6 (log-rank p=0.98) in survival analyses. In a multivariable Cox proportional hazards analysis, the risk of poor outcome (OHS 2-6) was greater in patients who had interventional treatment than in those who did not (hazard ratio 2.5, 95% CI 1.1-6.0) and was greater in patients with a larger AVM nidus (hazard ratio 1.3, 95% CI 1.1-1.7). The treated and untreated groups did not differ in time to an OHS score of 2 or more that was sustained until the end of the third year of follow-up, or in the spectrum of dependence as measured by the OHS at 1, 2, and 3 years of follow-up. INTERPRETATION Greater AVM size and interventional treatment were associated with worse short-term functional outcome for unruptured AVMs, but the longer-term effects of intervention are unclear.

Scottish Intracranial Vascular Malformation Study (SIVMS) Evaluation of Methods, ICD-10 Coding, and Potential Sources of Bias in a Prospective, Population-Based Cohort

Background and Purpose— The rarity of intracranial vascular malformations (IVMs) and the infrequency of their outcomes make large, prolonged cohort studies the best means to evaluate their frequency and prognosis. Methods— The Scottish Intracranial Vascular Malformation Study (SIVMS) is a prototype prospective, population-based study of adults resident in Scotland and diagnosed for the first time with an IVM after January 1, 1999. We evaluated the design of SIVMS using 2 complete years of data for adults with arteriovenous malformations (AVMs) of the brain. Results— A collaborative network of clinicians, radiologists, and pathologists, combined with coding of hospital discharge data and death certificates, recruited a cohort distributed in proportion to the Scottish population. Coding (with International Classification of Diseases, 10th Revision [ICD-10] codes Q28.2 and I60.8) had a sensitivity of 72% (95% CI, 61% to 80%) and a positive predictive value of 46% (95% CI, 38% to 55%) for detecting incident brain AVMs. Adults who were detected by coding alone were significantly (P <0.05) younger, more likely to present with hemorrhage, more frequently investigated with catheter angiography, and more likely to be treated. Adults recruited from tertiary referral centers were significantly more likely to be investigated with catheter angiography and to be treated. Using catheter angiography as a diagnostic requirement for brain AVMs significantly biases the cohort toward younger adults presenting with hemorrhage and receiving treatment. Conclusions— Population-based studies of IVM frequency and prognosis should use multiple overlapping sources of case ascertainment, and such studies of brain AVMs should not require catheter angiography to be the diagnostic standard.

Differences between intracranial vascular malformation types in the characteristics of their presenting haemorrhages: prospective, population-based study

Objective: To determine the imaging and demographic characteristics of intracranial haemorrhages, which are subsequently found to be due to an underlying intracranial vascular malformation (IVM). Methods: We compared the demographic and brain imaging characteristics of adults presenting with intracranial haemorrhage, subsequently found to be due to a brain arteriovenous malformation (BAVM), dural arteriovenous fistula (DAVF) or cavernous malformation (CM) in a prospective, population-based cohort of adults diagnosed for the first time with an IVM (The Scottish IVM Study (SIVMS)). Results: Of the 141 adults in SIVMS who presented with intracranial haemorrhage, those with CMs presented at a younger age and were less handicapped. A total of 115 (82%) had intracerebral haemorrhage (ICH) with or without subarachnoid, intraventricular or subdural extension. ICH without extension into other compartments accounted for all CM bleeds, but only 50% of BAVM and DAVF bleeds. Median haematoma volumes differed (Kruskal–Wallis, p<0.0001): ICH due to BAVM (16.0 cm3, inter-quartile range (IQR) 4.7 to 42.0) and DAVF (14.1 cm3, IQR 4.9 to 21.5) were similar, but CM haematoma volumes were smaller (median 1.8 cm3, IQR 1.3 to 4.3). These findings were robust in sensitivity analyses. Small haematoma volumes occurred among all IVM types; the largest haematoma volume due to CM was 12 cm3, and volumes of >34 cm3 were only due to BAVM. Conclusions: Intracranial haemorrhages found to be due to IVMs differ in adults’ age of presentation and clinical severity, as well as the volume and distribution of the haematoma within the brain compartments.

Seizure risk with AVM treatment or conservative management Prospective, population-based study

Objectives: To compare the risk of epileptic seizures in adults during conservative management or following invasive treatment for a brain arteriovenous malformation (AVM). Methods: We used annual general practitioner follow-up, patient questionnaires, and medical records surveillance to quantify the 5-year risk of seizures and the chances of achieving 2-year seizure freedom for adults undergoing AVM treatment compared to adults managed conservatively in a prospective, population-based observational study of adults in Scotland, newly diagnosed with an AVM in 1999–2003. Results: We identified 229 adults with a new diagnosis of an AVM, of whom two-thirds received AVM treatment (154/229; 67%) during 1,862 person-years of follow-up (median completeness of follow-up 97%). There was no significant difference in the proportions with a first or recurrent seizure over 5 years following AVM treatment, compared to the first 5 years following clinical presentation in conservatively managed adults, in analyses stratified by mode of presentation (intracerebral hemorrhage, 35% vs 26%, p = 0.5; seizure, 67% vs 72%, p = 0.6; incidental, 21% vs 10%, p = 0.4). For patients with epilepsy, the chances of achieving 2-year seizure freedom during 5-year follow-up were similar following AVM treatment (n = 39; 52%, 95% confidence interval [CI] 36% to 68%) or conservative management (n = 21; 57%, 95% CI 35% to 79%; p = 0.7). Conclusions: In this observational study, there was no difference in the 5-year risk of seizures with AVM treatment or conservative management, irrespective of whether the AVM had presented with hemorrhage or epileptic seizures.

Aberrant internal carotid artery in the middle-ear space.

The incidence of an aberrant internal carotid artery in the middle ear is approximately one per cent and most patients are asymptomatic. We present two patients with an aberrant internal carotid artery who presented with pulsatile tinnitus and an intra-tympanic mass. Here we discuss the clinical presentation, relevant radiographic investigations and further management of these patients.

Observer Agreement in the Angiographic Assessment of Arteriovenous Malformations of the Brain

Purpose— We aimed to determine intraobserver and interobserver agreement in the characterization of brain arteriovenous malformation (AVM) angioarchitecture on intra-arterial digital subtraction angiograms. Methods— Five experienced interventional neuroradiologists independently reviewed 40 anonymized angiograms obtained at the time of first-ever AVM diagnosis. The allocation of the films to observers was balanced for AVM size and complexity. Every observer was compared with himself and all the others by distributing the films in 2 batches 3 months apart. The observers used standard forms to collect both quantitative and categorized qualitative angiographic data. To measure agreement we used the kappa statistic (&kgr;) for nominal data, weighted &kgr; for ordinal and discrete interval data, and Bland & Altman analysis for continuous data. Results— Intraobserver agreement was generally moderate to substantial, with 95% confidence intervals ranging from fair to almost perfect. However, for every characteristic, interobserver agreement was less than intraobserver agreement. Interobserver agreement was generally slight to moderate, with 95% confidence intervals ranging from less than chance to almost perfect. Conclusion— This study demonstrates the need for robust and generalizeable definitions of AVM angioarchitecture and methods of nidus size measurement—with proof of good intraobserver and interobserver agreement—for future efforts to understand the prognosis and best treatment of AVMs.

The Presentation and Clinical Course of Intracranial Developmental Venous Anomalies in Adults A Systematic Review and Prospective, Population-Based Study

Background and Purpose— Reported risks of hemorrhage from intracranial developmental venous anomalies (DVAs) vary, so we investigated this in a systematic review and population-based study. Methods— We systematically reviewed the literature (Ovid Medline and Embase to November 7, 2007) and selected studies of ≥20 participants with ≥1 DVA(s) that described their clinical presentation and/or their clinical course over a specified follow-up period. We also identified every adult first diagnosed with a DVA in Scotland from 1999 to 2003 and followed them in a prospective, population-based study. Results— Of 2068 articles detected by the literature search, 15 met our inclusion criteria and described clinical presentation, 8 of which also described the clinical course of DVAs. In the 15 studies of 714 people first presenting with a DVA, 61% were incidental findings, the mode of presentation was unclear in 23%, 6% presented with nonhemorrhagic focal neurological deficit, 6% had caused symptomatic hemorrhage, 4% were associated with epileptic seizure, and <1% were associated with infarction. In studies of the clinical course of 422 people with a DVA, the hemorrhage rate after first presentation ranged from 0% to 1.28% per year. In the population-based study of 93 adults with DVAs, 98% were incidental, 1% presented with symptomatic hemorrhage, and 1% presented with an infarct, but there were no symptomatic hemorrhages or infarcts in 492 person-years of follow-up (0% per person-year; 95% CI, 0% to 0.7%). Conclusions— Intracranial DVAs have a benign presentation and clinical course.

Patterns of Brain Arteriovenous Malformation Treatment Prospective, Population-Based Study

Background and Purpose— The extent of variation in the interventional treatment of brain arteriovenous malformations (AVMs) is unknown, so we explored patterns of treatment at 4 neuroscience centers in one European country. Methods— We included every participant with an AVM in a prospective, population-based cohort study of adults aged ≥16 years residing in Scotland at the time of AVM diagnosis in 1999 to 2003. Results— Only 11 (5%) of the 229 adults were not managed at a neuroscience center. Adults who received interventional treatment were younger (median, 43 versus 54 years), more likely to have presented with hemorrhage (OR, 2.8; 95% CI, 1.6 to 4.9), and had smaller AVMs (median nidus diameter, 2 cm versus 3 cm; P=0.003) than those who did not. Adults seen at the 4 centers only differed in AVM Spetzler-Martin grade (P=0.04). The 4 centers did not differ in the proportion of adults with AVMs who received interventional treatment (P=0.16), but they differed in the Spetzler-Martin grade of the AVMs they treated (Grades III to IV, P=0.01) and the interventional treatments used (P=0.004). The 2 largest centers differed from each other in the likelihood of surgical resection (OR, 0.2; 95% CI, 0.1 to 0.6) and stereotactic radiosurgery (OR, 2.8; 95% CI, 1.3 to 6.1), and the choice of modality varied within some Spetzler-Martin grades. Conclusions— Patient characteristics and patterns of AVM interventional treatment differ between neuroscience centers in the same population necessitating careful consideration of these factors when comparing one hospital’s outcome with another.

Persistent hypoglossal artery--an increased risk for intracranial aneurysms?

A 53-year-old hypertensive female smoker presented with a WFNS grade II subarachnoid haemorrhage. Angiography showed a left persistent hypoglossal artery with multiple intracranial aneurysms. She underwent successful coil embolisation of the ruptured aneurysm. We reviewed the literature on persistent hypoglossal artery and found 26% of them have associated intracranial aneurysms. This controversial topic is discussed.