Robin Sellar

Cerebral angiographic risk in mild cerebrovascular disease.

We review the eight prospective and seven retrospective studies from which it is possible to derive the complication rate of conventional cerebral angiography for patients with mild ischemic cerebrovascular disease who are potential candidates for carotid endarterectomy. Three studies of intravenous and one of intra-arterial digital subtraction angiography are also examined. An overview of the results suggests that the risk of a neurological complication (TIA or stroke) is about 4% and that a permanent neurological deficit (disabling stroke) occurs in about 1%. The mortality rate is very low (less than 0.1%). Systemic complications are not infrequent, particularly with intravenous digital subtraction angiography. The complication rate of cerebral angiography must be considered when evaluating the risks of carotid endarterectomy in patients with ischemic cerebrovascular disease.

The pulvinar sign on magnetic resonance imaging in variant Creutzfeldt-Jakob disease.

BACKGROUND There is a need for an accurate non-invasive diagnostic test for variant Creutzfeldt-Jakob disease (vCJD). We investigated the sensitivity and specificity of bilateral pulvinar high signal on magnetic resonance imaging (MRI) for the diagnosis of vCJD. METHODS MRI from patients with vCJD and controls (patients with suspected CJD) were analysed. Scans were reviewed on two separate occasions by two neuroradiologists and scored for the distribution of changes, and likely final diagnosis. Scans from vCJD cases were reassessed to reach a consensus on all abnormalities. FINDINGS We analysed 36 patients and 57 controls. vCJD patients were correctly identified based on bilateral pulvinar high signal in 29 of 36 and 32 of 36 cases on the first assessment by the two radiologists, and 32 of 36 and 31 of 36 on their second assessment. Bilateral increased pulvinar signal was identified in one of 57 and one of 57 controls on the first assessment and two of 57 and three of 57 controls on the second assessment. These reported changes in controls were graded as minimal/equivocal in six of seven patients and moderate in one (<0.5% of all control assessments). 80% of the assessments in vCJD cases were graded as moderate or substantial. On consensus review, 28 of 36 cases and none of 57 controls had prominent bilateral pulvinar signal-sensitivity 78% (95% CI 60-90%) and specificity 100% (95% CI 94-100%). Other common MRI features of vCJD were medial thalamic and periaqueductal grey matter high signal, and the notable absence of cerebral atrophy. Pulvinar high signal correlated with histological gliosis. INTERPRETATION In the appropriate clinical context the MRI identification of bilaterally increased pulvinar signal is a useful non-invasive test for the diagnosis of vCJD.

Equivalence of measurements of carotid stenosis. A comparison of three methods on 1001 angiograms. European Carotid Surgery Trialists' Collaborative Group.

There is confusion about how carotid stenosis should be measured on angiograms. If the results of research based on different methods of measurement of stenosis are to be discussed and the results of clinical trials properly applied to routine clinical practice, measurements made by the different methods must be formally compared. Methods The method of measurement of stenosis used in the European Carotid Surgery Trial (ECST), that used in the North American Symptomatic Carotid Endarterectomy Trial (NASCET), and a method based on measurement of the common carotid (CC) artery lumen diameter were compared. Carotid stenosis was measured by two observers, working independently and using the three different methods of measurement, on the angiographic view of the symptomatic carotid stenosis that showed the most severe disease in 1001 patients from the ECST. Results The results of using the ECST and CC methods differed from those of using the NASCET method in the classification of stenoses as mild (0% to 29%), moderate (30% to 69%), or severe (70% to 99%) in 51% of measurements. The ECST and CC methods indicated that twice as many stenoses were severe as did the NASCET method, and classified less than a third of the number of stenoses as mild. The results of the ECST and CC methods differed from each other in 15% of measurements. The relations between measurements made by each method to those made by the others were approximately linear, so a simple equation could be derived to convert measurements made by one method to measurements made by the others. Conclusions There were major and clinically important disparities between measurements of stenosis made using different methods of measurement on the same angiograms. However, it is possible to convert measurements made by one method to those of another using a simple arithmetic equation.

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.

Hydrogel-coated coils versus bare platinum coils for the endovascular treatment of intracranial aneurysms (HELPS): a randomised controlled trial

BACKGROUND Coated coils for endovascular treatment of cerebral aneurysm were developed to reduce recurrence and retreatment rates, and have been in clinical use for 8-9 years without robust evidence to determine their efficacy. We assessed the efficacy and safety of hydrogel-coated coils. METHODS This randomised trial was undertaken in 24 centres in seven countries. Patients aged 18-75 years with a previously untreated ruptured or unruptured cerebral aneurysm of 2-25 mm in maximum diameter were randomly allocated (1:1) to aneurysm coiling with either hydrogel-coated coils or standard bare platinum coils (control). Randomisation was done with a computer-generated sequence, stratified by aneurysm size, shape, and dome-to-neck ratio; intention to use assist device; and by region. Participants and those assessing outcomes were masked to allocation. Analysis was by modified intention to treat (excluding missing data). Primary outcome was a composite of angiographic and clinical outcomes at 18-month follow-up. We also did prespecified subgroup analyses of characteristics likely to be relevant to angiographic outcome. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN30531382. FINDINGS 249 patients were allocated to the hydrogel coil group and 250 to the control group. In 44 of 467 patients for whom an 18-month composite primary outcome was unavailable, 6-month angiographic results were used. 70 (28%) patients in the hydrogel group and 90 (36%) control patients had an adverse composite primary outcome, giving an absolute reduction in the proportion of adverse composite primary outcomes with hydrogel of 7·0% (95% CI -1·6 to 15·5), odds ratio (OR) 0·73 (0·49-1·1, p=0·13). In a prespecified subgroup analysis in recently ruptured aneurysms, there were more adverse composite primary outcomes in the control group than in the hydrogel group-OR 2·08 (1·24-3·46, p=0·014). There were 8·6% fewer major angiographic recurrences in patients allocated to hydrogel coils-OR 0·7 (0·4-1·0, p=0·049). There were five cases of unexplained hydrocephalus in not-recently-ruptured aneurysms in the hydrogel coil group and one case in the control group. INTERPRETATION Whether use of hydrogel coils reduces late aneurysm rupture or improves long-term clinical outcome is not clear, but our results indicate that their use lowers major recurrence. FUNDING MicroVention Inc.

Evaluation of investigations to diagnose the cause of dizziness in elderly people: a community based controlled study.

Abstract Objective: To compare the findings in dizzy elderly people with those in controls of a similar age to identify which investigations differentiate dizzy from non-dizzy patients and to design an investigational algorithm. Design: Community based study of clinical and laboratory findings in dizzy and control elderly people. Setting: Research outpatient clinic at a teaching hospital. Subjects: 149 dizzy and 97 control subjects aged over 65 years recruited from a community survey and articles in the local press. Main outcome measures: Findings on physical examination, blood testing, electrocardiography (at rest and over 24 hours), electronystagmography, posturography, and magnetic resonance imaging of head and neck (125 (84%) dizzy subjects and 86 (89%) controls); hospital anxiety and depression score; responses to hyperventilation, carotid sinus massage, and the Hallpike manoeuvre. Results: Blood profile, electrocardiography, electronystagmography, and magnetic resonance imaging failed to distinguish dizzy from control subjects because of the frequency of asymptomatic abnormalities in controls. Posturography and clinical assessment (physical examination, dizziness provocation, and psychological assessment) showed significant differences between the groups. A cause of the dizziness was identified from clinical diagnostic criteria based on accepted definitions in 143 subjects, with 126 having more than one cause. The most common diagnoses were central vascular disease (105) and cervical spondylosis (98), often accompanied by poor vision and anxiety. Conclusion: Expensive investigations are rarely helpful in dizzy elderly people. The cause of the dizziness can be diagnosed in most cases on the basis of a thorough clinical examination without recourse to hospital referral. Key messages Expensive investigations are rarely helpful in the diagnosis of dizziness in elderly people The most common causes of dizziness in older people are central vascular disease and cervical spondylosis Poor vision and anxiety often accompany but are rarely the sole cause of dizziness These findings point to a definitive role for the general practitioner in the assessment of dizzy elderly patients

Brain Abnormalities Demonstrated by Magnetic Resonance Imaging in Adult IDDM Patients With and Without a History of Recurrent Severe Hypoglycemia

OBJECTIVE Previous studies of a cohort of 100 patients with IDDM have shown that a history of recurrent severe hypoglycemia is associated with a modest impairment of cognitive function. The aim of the present study was to determine whether IDDM patients with and without a history of severe hypoglycemia have lesions in the brain that are identifiable by magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) and to investigate the putative relationship of any structural brain abnormalities with cognitive function. RESEARCH DESIGN AND METHODS MRI and MRS of the brain were performed in 22 patients from the original cohort. Eleven IDDM patients with no history of severe hypoglycemia (group A) were compared with 11 IDDM patients who had a history of five or more episodes of severe hypoglycemia (group B). RESULTS Nine patients (41%) had abnormal scans. Two types of abnormalities were observed: high-intensity rounded lesions, > 3 mm in diameters, distributed in the periventricular white matter (leukoaraiosis) in four patients; and cortical atrophy in five patients. Five patients in group B had cortical atrophy, whereas no patient in group A demonstrated this feature (P < 0.05). MRS of the frontal and parietal lobes showed no differences in the N-acetyl aspartate/creatine or N-acetyl aspartate/choline ratios between groups A and B. Patients with cortical atrophy showed a nonsignificant trend toward reduced performance on Rapid Visual Information Processing. CONCLUSIONS Brain abnormalities demonstrated by MRI are common in patients with IDDM of long duration and are suggestive of premature aging of the brain. IDDM per se may be an important pathogenic factor, but a significant association was observed between a history of recurrent severe hypoglycemia and cortical atrophy, which may be related to the modest impairment of cognitive function that has been reported previously.

HydroCoil Endovascular Aneurysm Occlusion and Packing Study (HELPS Trial): Procedural Safety and Operator-Assessed Efficacy Results

BACKGROUND AND PURPOSE: Coated coils have been in clinical use for several years without robust evidence to determine their safety/efficacy. The HydroCoil Endovascular Aneurysm Occlusion and Packing Study (HELPS) addresses this deficiency for the HydroCoil embolic system. This article reports periprocedural safety/operator-assessed angiographic results from HELPS. MATERIALS AND METHODS: Patients were randomized to the hydrogel coil or control arms by using concealed allocation with minimization matching groups. Any bare platinum coils were allowed in the control arm, and assist devices could be used as clinically required. Both recently ruptured and not recently ruptured/unruptured aneurysms were included. Analysis was on an intention-to-treat basis. RESULTS: Four hundred ninety-nine patients were recruited. Coiling was successful in 98.6%. Mean aneurysm size was 6.5 mm (26% were ≥10 mm), 53% were recently ruptured aneurysms, and an assist device was used in 46%. Seventy procedural adverse events were reported in hydrogel coils and 86 in control arms. The 3-month mortality rate was 3.6% in hydrogel coils and 2.0% in control arms; the difference was not significant (P = .6). There was a lower 2-month mortality rate in the HELPS subarachnoid hemorrhage cohort (4.1%) than would be anticipated from the International Subarachnoid Aneurysm Trial (7%). There was a trend toward increased adverse events when assist devices were used, which was substantial for stents deployed in recently ruptured aneurysms. Ninety-six percent of patients discharged were World Federation of Neurosurgeons grade 0–2 at discharge. No difference was found between arms in the operator assessment of angiographic occlusions (P = .3). CONCLUSION: These HELPS results reinforce coiling as an effective treatment for aneurysms, with an excellent technical success rate. Hydrogel coils can be used in a wide spectrum of aneurysms with a risk profile equivalent to that of bare platinum.

Outcome, observer reliability, and patient preferences if CTA, MRA, or Doppler ultrasound were used, individually or together, instead of digital subtraction angiography before carotid endarterectomy

Objectives: To evaluate the accuracy of routinely available non-invasive tests (spiral computed tomographic angiography (CTA), time of flight magnetic resonance angiography (MRA), and colour Doppler ultrasound (DUS)), individually and together, compared with intra-arterial digital subtraction angiography (DSA) in patients with symptomatic tight carotid stenosis; and to assess the effect of substituting non-invasive tests for DSA on outcome, interobserver variability, and patient preference. Methods: Patients referred from a neurovascular clinic were subjected prospectively to DUS imaging. The operator was blind to symptoms. Patients with a tight carotid stenosis on the symptomatic side were admitted for DSA. CTA and MRA were performed during the admission. The CTA, MRA, and DSA films were each read independently by two of six experienced radiologists, blind to all other data. Results: 67 patients were included (34 had all four imaging procedures). DUS, CTA, and MRA all agreed with DSA in the diagnosis of operable v non-operable disease in about 80% of patients. CTA tended to underestimate (sensitivity 0.65, specificity 1.0), MRA to overestimate (sensitivity 1.0, specificity 0.57), and DUS to agree most closely with (sensitivity 0.85, specificity 0.71) the degree of stenosis as shown by DSA. When using any two of the three non-invasive tests in combination, adding the third if the first two disagreed would result in very few misdiagnoses (about 6%). MRA had similar interobserver variability to CTA (both worse than DSA). Patients preferred CTA over MRA and DSA. Conclusions: DUS, CTA, and MRA all show similar accuracy in the diagnosis of symptomatic carotid stenosis. No technique on its own is accurate enough to replace DSA. Two non-invasive techniques in combination, and adding a third if the first two disagree, appears more accurate, but may still result in diagnostic errors.

Outcome After Conservative Management or Intervention for Unruptured Brain Arteriovenous Malformations

IMPORTANCE Whether conservative management is superior to interventional treatment for unruptured brain arteriovenous malformations (bAVMs) is uncertain because of the shortage of long-term comparative data. OBJECTIVE To compare the long-term outcomes of conservative management vs intervention for unruptured bAVM. DESIGN, SETTING, AND POPULATION Population-based inception cohort study of 204 residents of Scotland aged 16 years or older who were first diagnosed as having an unruptured bAVM during 1999-2003 or 2006-2010 and followed up prospectively for 12 years. EXPOSURES Conservative management (no intervention) vs intervention (any endovascular embolization, neurosurgical excision, or stereotactic radiosurgery alone or in combination). MAIN OUTCOMES AND MEASURES Cox regression analyses, with multivariable adjustment for prognostic factors and baseline imbalances if hazards were proportional, to compare rates of the primary outcome (death or sustained morbidity of any cause by Oxford Handicap Scale [OHS] score ≥2 for ≥2 successive years [0 = no symptoms and 6 = death]) and the secondary outcome (nonfatal symptomatic stroke or death due to bAVM, associated arterial aneurysm, or intervention). RESULTS Of 204 patients, 103 underwent intervention. Those who underwent intervention were younger, more likely to have presented with seizure, and less likely to have large bAVMs than patients managed conservatively. During a median follow-up of 6.9 years (94% completeness), the rate of progression to the primary outcome was lower with conservative management during the first 4 years of follow-up (36 vs 39 events; 9.5 vs 9.8 per 100 person-years; adjusted hazard ratio, 0.59; 95% CI, 0.35-0.99), but rates were similar thereafter. The rate of the secondary outcome was lower with conservative management during 12 years of follow-up (14 vs 38 events; 1.6 vs 3.3 per 100 person-years; adjusted hazard ratio, 0.37; 95% CI, 0.19-0.72). CONCLUSIONS AND RELEVANCE Among patients aged 16 years or older diagnosed as having unruptured bAVM, use of conservative management compared with intervention was associated with better clinical outcomes for up to 12 years. Longer follow-up is required to understand whether this association persists.