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 >or=20 participants with >or=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.

Smart Brushing for Parallel Coordinates.

The Parallel Coordinates plot is a popular tool for the visualization of high-dimensional data. One of the main challenges when using parallel coordinates is occlusion and overplotting resulting from large data sets. Brushing is a popular approach to address these challenges. Since its conception, limited improvements have been made to brushing both in the form of visual design and functional interaction. We present a set of novel, smart brushing techniques that enhance the standard interactive brushing of a parallel coordinates plot. We introduce two new interaction concepts: Higher-order, sketch-based brushing, and smart, data-driven brushing. Higher-order brushes support interactive, flexible, n-dimensional pattern searches involving an arbitrary number of dimensions. Smart, data-driven brushing provides interactive, real-time guidance to the user during the brushing process based on derived meta-data. In addition, we implement a selection of novel enhancements and user options that complement the two techniques as well as enhance the exploration and analytical ability of the user. We demonstrate the utility and evaluate the results using a case study with a large, high-dimensional, real-world telecommunication data set and we report domain expert feedback from the data suppliers.

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 >or=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.

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.

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 >or=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.

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.

Cost-utility analysis of vagus nerve stimulators for adults with medically refractory epilepsy.

INTRODUCTION: The cost-utility of vagus nerve stimulator (VNS) devices for medically refractory epilepsy has yet to be estimated. METHODS: Using a meta-analysis of randomised controlled trials of VNS, we estimate that six people require implantation in order for one person to experience a 50% reduction in seizure frequency. Costs averted from improved epilepsy control were ascertained from published literature. Values for health states were obtained from a series of 42 seizure clinic attenders using time trade-off techniques and the EQ-5D health status instrument. The cost per quality adjusted life year gained was estimated and the values obtained were tested in a sensitivity analysis. RESULTS: Improved epilepsy control averted, on average, 745 pounds sterling health care costs per annum. People with epilepsy had great difficulty performing the time trade-off experiment, but those who managed to complete the task valued a 50% reduction in their own seizure frequency at 0.285 units. For a programme of six implants, the baseline model estimated the cost per quality adjusted life year gained at 28,849 pounds sterling. The most favourable estimate was equal to 4785 pounds sterling per quality adjusted life year gained, assuming that the number needed to treat was similar to published series in which one response was obtained for every three implants. The least favourable estimate was equal to 63,000 pounds sterling per quality adjusted life year gained, when EQ-5D utility values were used. The cost per quality adjusted life year gained was not sensitive to changes in length of stay, nor complication rates, but was significantly influenced by cost of device and device battery life expectancy. CONCLUSION: There is not a strong economic argument against a programme of VNS implantation, although care should be taken to try and identify and treat those most likely to benefit.

Untreated clinical course of cerebral cavernous malformations: a prospective, population-based cohort study.

BACKGROUND: Cerebral cavernous malformations (CCMs) are prone to bleeding but the risk of intracranial haemorrhage and focal neurological deficits, and the factors that might predict their occurrence, are unclear. We aimed to quantify these risks and investigate whether they are affected by sex and CCM location. METHODS: We undertook a population-based study using multiple overlapping sources of case ascertainment (including a Scotland-wide collaboration of neurologists, neurosurgeons, stroke physicians, radiologists, and pathologists, as well as searches of registers of hospital discharges and death certificates) to identify definite CCM diagnoses first made in Scottish residents between 1999 and 2003, which study neuroradiologists independently validated. We used multiple sources of prospective follow-up both to identify outcome events (which were assessed by use of brain imaging, by investigators masked to potential predictive factors) and to assess adults' dependence. The primary outcome was a composite of intracranial haemorrhage or focal neurological deficits (not including epileptic seizure) that were definitely or possibly related to CCM. FINDINGS: 139 adults had at least one definite CCM and 134 were alive at initial presentation. During 1177 person-years of follow-up (completeness 97%), for intracranial haemorrhage alone the 5-year risk of a first haemorrhage was lower than the risk of recurrent haemorrhage (2·4%, 95% CI 0·0-5·7 vs 29·5%, 4·1-55·0; p<0·0001). For the primary outcome, the 5-year risk of a first event was lower than the risk of recurrence (9·3%, 3·1-15·4 vs 42·4%, 26·8-58·0; p<0·0001). The annual risk of recurrence of the primary outcome declined from 19·8% (95% CI 6·1-33·4) in year 1 to 5·0% (0·0-14·8) in year 5 and was higher for women than men (p=0·01) but not for adults with brainstem CCMs versus CCMs in other locations (p=0·17). INTERPRETATION: The risk of recurrent intracranial haemorrhage or focal neurological deficit from a CCM is greater than the risk of a first event, is greater for women than for men, and declines over 5 years. This information can be used in clinical practice, but further work is needed to quantify risks precisely in the long term and to understand why women are at greater risk of recurrence than men. FUNDING: UK Medical Research Council, Chief Scientist Office of the Scottish Government, and UK Stroke Association.

Ocular scanning and perceptual size distortion in hemispatial neglect: effects of prism adaptation and sequential stimulus presentation.

When asked to compare two lateralized shapes for horizontal size, neglect patients often indicate the left stimulus to be smaller. Gainotti and Tiacci (1971) hypothesized that this phenomenon might be related to a rightward bias in the patients' gaze. This study aimed to assess the relation between this size underestimation and oculomotor asymmetries. Eye movements were recorded while three neglect patients judged the horizontal extent of two rectangles. Two experimental manipulations were performed to increase the likelihood of symmetrical scanning of the stimulus display. The first manipulation entailed a sequential, rather than simultaneous presentation of the two rectangles. The second required adaptation to rightward displacing prisms, which is known to reduce many manifestations of neglect. All patients consistently underestimated the left rectangle, but the pattern of verbal responses and eye movements suggested different underlying causes. These include a distortion of space perception without ocular asymmetry, a failure to view the full leftward extent of the left stimulus, and a high-level response bias. Sequential presentation of the rectangles and prism adaptation reduced ocular asymmetries without affecting size underestimation. Overall, the results suggest that leftward size underestimation in neglect can arise for a number of different reasons. Incomplete leftward scanning may perhaps be sufficient to induce perceptual size distortion, but it is not a necessary prerequisite.