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Background and Purpose: The PROGRESS trial (Perindopril Protection Against Recurrent Stroke Study) conducted in the early 1990s showed that blood pressure (BP) lowering therapy reduced the risks of recurrent stroke by about 50% after spontaneous intracerebral hemorrhage (ICH). However, the ICH subgroup was a minority, and trial cohorts are invariably selective. Therefore, it is unclear whether the impact of BP control on risk of recurrent stroke in ICH observed in PROGRESS would be as great in real-world practice. Methods: We compared BP control (mean BP during study follow-up) and risks of recurrent stroke after first-ever primary ICH in 2 colocated population-based studies before and after the PROGRESS trial (1995–2001) in Oxfordshire: Oxfordshire Community Stroke Project (OCSP; 1981–1986) and OXVASC (Oxford Vascular Study; 2002–2018). Results: Two hundred seventy-seven patients (753 patient-years of follow-up) with first-ever primary ICH were ascertained in OXVASC and OCSP. Baseline systolic BP was comparable between the 2 studies (mean/SD=183.8/36.5 in OXVASC versus 178.1/38.2 in OCSP, P =0.30) but among one hundred thirty-seven 90-day survivors, mean BP during follow-up was substantially lower in OXVASC versus OCSP (135.2/16.4 versus 157.3/17.8, P P =0.006), predominantly driven by a reduction at younger ages (5-year risk at age P =0.001; hazard ratio, 0.14 [0.04–0.54]). Conclusions: Risks of recurrent stroke after primary ICH have fallen significantly in Oxfordshire over the past 4 decades, coinciding with substantial improvements in BP control during follow-up.

Whenever there is widespread uncertainty about the balance between the benefits and harms of a therapeutic intervention—which clearly exists for the timing of when to start invasive ventilation judging from Torjesen’s article1—the solution is generally …

BackgroundCalls are increasing for widespread SARS-CoV-2 infection testing of people from populations with a very low prevalence of infection. We quantified the impact of less than perfect diagnostic test accuracy on populations, and on individuals, in low prevalence settings, focusing on false positives and the role of confirmatory testing.MethodsWe developed a simple, interactive tool to assess the impact of different combinations of test sensitivity, specificity and infection prevalence in a notional population of 100,000. We derived numbers of true positives, true negatives, false positives and false negatives, positive predictive value (PPV – the percentage of test positives that are true positives) and overall test accuracy for three testing strategies: (1) single test for all; (2) add repeat testing in test positives; (3) add further repeat testing in those with discrepant results. We also assessed the impact on test results for individuals having one, two or three tests under these three strategies.ResultsWith sensitivity of 80%, infection prevalence of 1 in 2,000, and specificity 99.9% on all tests, PPV in the tested population of 100,000 will be only 29% with one test, increasing to > 99.5% (100% when rounded to the nearest %) with repeat testing in strategies 2 or 3. More realistically, if specificity is 95% for the first and 99.9% for subsequent tests, single test PPV will be only 1%, increasing to 86% with repeat testing in strategy 2, or 79% with strategy 3 (albeit with 6 fewer false negatives than strategy 2). In the whole population, or in particular individuals, PPV increases as infection becomes more common in the population but falls to unacceptably low levels with lower test specificity.ConclusionTo avoid multiple unnecessary restrictions on whole populations, and in particular individuals, from widespread population testing for SARS-CoV-2, the crucial roles of extremely high test specificity and of confirmatory testing must be fully appreciated and incorporated into policy decisions.

Richard Christopher David Greenhall devoted the whole of his professional life as a neurologist to working exclusively in the NHS. Never one for pushing himself forward, he was the sort of full time consultant who provides the rock on which the NHS stands, totally dedicated to his clinical service and to his patients. Richard was a Birmingham boy of Welsh heritage who after leaving King Edward’s School went up to Cambridge in 1962, initially to read natural sciences, although he soon switched to medicine. After clinical training at St Thomas’ Hospital in London, and junior hospital doctor posts in Oxford, Bristol, and London, he started training in neurology under Bryan Matthews in Oxford. Completing his DM thesis in 1975, he flirted …

BACKGROUND: The incidence of stroke is predicted to rise because of the rapidly ageing population. However, over the past two decades, findings of randomised trials have identified several interventions that are effective in prevention of stroke. Reliable data on time-trends in stroke incidence, major risk factors, and use of preventive treatments in an ageing population are required to ascertain whether implementation of preventive strategies can offset the predicted rise in stroke incidence. We aimed to obtain these data. METHODS: We ascertained changes in incidence of transient ischaemic attack and stroke, risk factors, and premorbid use of preventive treatments from 1981-84 (Oxford Community Stroke Project; OCSP) to 2002-04 (Oxford Vascular Study; OXVASC). FINDINGS: Of 476 patients with transient ischaemic attacks or strokes in OXVASC, 262 strokes and 93 transient ischaemic attacks were incident events. Despite more complete case-ascertainment than in OCSP, age-adjusted and sex-adjusted incidence of first-ever stroke fell by 29% (relative incidence 0.71, 95% CI 0.61-0.83, p=0.0002). Incidence declined by more than 50% for primary intracerebral haemorrhage (0.47, 0.27-0.83, p=0.01) but was unchanged for subarachnoid haemorrhage (0.83, 0.44-1.57, p=0.57). Thus, although 28% more incident strokes (366 vs 286) were expected in OXVASC due to demographic change alone (33% increase in those aged 75 or older), the observed number fell (262 vs 286). Major reductions were recorded in mortality rates for incident stroke (0.63, 0.44-0.90, p=0.02) and in incidence of disabling or fatal stroke (0.60, 0.50-0.73, p

Suicide is one of the ten most common causes of death for both men and women in GreatBritain.1 Psychiatric disorders are the main risk factor, but numerous studies have also identified physical illness as an important contributory factor.1 2 Although it is considered mandatory to enquire about suicidal ideation in psychiatric consultations, this is seldom part of a medical assessment. We aimed to examine suicidal ideation in a consecutive series of patients who had been newly referred to general neurology outpatient clinics. The study was approved by the local research ethics committee. As part of another study,3 300 of 312 consecutive new patients at the general neurology outpatient clinics at the Western General Hospital, Edinburgh, were interviewed using the primary care evaluation of mental disorders (PRIME-MD) structured psychiatric interview schedule.4 As part of the interview …

Background: Although the symptoms of unilateral "medically unexplained" or "functional" weakness and sensory disturbance present commonly to neurologists, little is known about their long term prognosis. Objective: To determine the long term outcome of functional weakness and sensory disturbance. Patients: A previously assembled cohort of 60 patients seen as inpatients by consultant neurologists in Edinburgh between 1985 and 1992 and diagnosed as having unilateral functional weakness or sensory disturbance. Methods: Current symptoms, disability, and distress were assessed by postal questionnaire to the patients and their family doctors. Results: Follow up data relating to mortality were obtained in 56 patients (93%) and to current diagnosis in 48 patients (80%). Patient questionnaire data were obtained in 42 patients (70%). The median duration of follow up was 12.5 years (range 9 to 16). Thirty five of the 42 patients (83%) still reported weakness or sensory symptoms, and the majority reported limitation of physical function, distress, and multiple other somatic symptoms. Twenty nine per cent had taken medical retirement. An examination of baseline predictors indicated that patients who had sensory symptoms had better functioning at follow up than those who had weakness. Only one patient had developed a neurological disorder which, in hindsight, explained the original presentation. Another patient had died of unrelated causes. Conclusions: Many patients assessed by neurologists with unilateral functional weakness and sensory symptoms as inpatients remain symptomatic, distressed, and disabled as long as 12 years after the original diagnosis. These symptoms are only rarely explained by the subsequent development of a recognisable neurological disorder in the long term.

OBJECTIVE: To identify risk factors for operative stroke and death from carotid endarterectomy. DESIGN: Systematic review of all studies published since 1980 which related risk of stroke and death to various preoperative clinical and angiographic characteristics, including unpublished data on 1729 patients from the European carotid surgery trial. MAIN OUTCOME MEASURE: Operative risk of stroke and death. RESULTS: Thirty six published studies fulfilled our criteria. The effect of 14 potential risk factors was examined. The odds of stroke and death were decreased in patients with ocular ischaemia alone (amaurosis fugax or retinal artery occlusion) compared with those with cerebral transient ischaemic attack or stroke (seven studies; odds ratio 0.49; 95% confidence interval 0.37 to 0.66; P < 0.00001). The odds were increased in women (seven studies; 1.44; 1.14 to 1.83; P < 0.005), subjects aged > or = 75 years (10 studies: 1.36; 1.09 to 1.71; P < 0.01), and with systolic blood pressure > 180 mm Hg (four studies; 1.82; 1.37 to 2.41; P < 0.0001), peripheral vascular disease (one study; 2.19; 1.40 to 3.60; P < 0.0005), occlusion of the contralateral internal carotid artery (14 studies; 1.91; 1.35 to 2.69; P < 0.0001), stenosis of the ipsilateral internal carotid siphon (five studies; 1.56; 1.03 to 2.36; P = 0.02), and stenosis of the ipsilateral external carotid artery (one study; 1.61; 1.05 to 2.47; P = 0.03). Operative risk was not significantly related to presentation with cerebral transient ischaemic attack versus stroke, diabetes, angina, recent myocardial infarction, current cigarette smoking, or plaque surface irregularity at angiography. Multiple regression analysis of data from the European carotid surgery trial identified cerebral versus ocular events at presentation, female sex, systolic hypertension, and peripheral vascular disease as independent risk factors. CONCLUSIONS: The risk of stroke and death from carotid endarterectomy is related to several clinical and angiographic characteristics. These observations may help clinicians to estimate operative risks for individual patients and will also facilitate more meaningful comparison of the operative risks of different surgeons or at different institutions by allowing some adjustment for differences in case mix.

Background: Several studies have shown serum urate to be an independent risk factor for vascular disease, but others have not, although a stronger association in women than in men has been a consistent finding. Studies of stroke patients have shown possible associations between urate level and stroke severity, but there have been no large cohort studies of the effect of urate on the long-term risk of future vascular events in patients with a transient ischaemic attack (TIA) or stroke. We studied this relationship in 2 independent cohorts. Methods: Individual data on 15,483 patient-years of follow-up from the UK-TIA trial (13,182 patient-years) and the Oxford TIA study (2,301 patient-years) were analyzed. Hazard ratios (per unit increase of baseline urate in mg/dl) for the risks of stroke and acute coronary events (ACE) were obtained from Cox models stratified by study, with and without adjustment for potential confounders. Potential interactions between urate and baseline characteristics were also assessed. Results: Linear associations between urate and risk of ACE were found in both studies: pooled age- and sex-adjusted hazard ratio = 1.17, 95% CI 1.06–1.30, per unit increase of urate (p = 0.003). Sex, body mass index and previous myocardial infarction or angina were effect modifiers, but only the effect of sex remained after adjustment for other risk factors (p = 0.002), with a 5th:1st quintile hazard ratio of 4.23 (1.97–9.07, p < 0.0001) in women and 1.09 (0.70–1.71, p = 0.69) in men. These findings were consistent across the 2 studies. No associations were found between urate level and either risk or severity of stroke. Conclusions: High urate levels were independent predictors of long-term risk of ACE in women who had a TIA or stroke, but not in men, in 2 independent studies. Urate levels could be useful in identifying women at high risk of coronary events in routine practice.

We developed a model identifying patients with previous cerebral ischaemia at increased risk of intracerebral haemorrhage (ICH). Based on data from eight cohorts, 107 ICHs were found to have occurred among 12 648 patients. Multivariate Cox regression analysis identified the following predictors: age (> or = 60 years, hazard ratio (HR) 2.07), blood glucose level (> or = 7 mmol/l, HR 0.33), systolic blood pressure (> or = 140 mm Hg, HR 2.17), and antihypertensive drugs (HR 1.53). The highest risk quartile was associated with five times more ICHs than the lowest quartile.

The use of three methods of measuring carotid stenosis, which produce different values on the same angiograms, has caused confusion and reduced the generalizability of the results of research. If the results of future studies are to be properly applied to clinical practice, and if noninvasive methods of imaging are to be properly validated against angiography, a single, standard method of measurement of stenosis on angiograms must be adopted. This standard method should be selected on the bases of its ability to predict risk of ipsilateral carotid distribution ischemic stroke and its reproducibility. The method of measurement of carotid 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 the measurement of the common carotid (CC) lumen diameter were studied. Their use in the prediction of ipsilateral carotid distribution ischemic stroke was assessed in 1001 consecutively selected patients randomly assigned to medical treatment in the ECST. Carotid stenosis was measured by two observers working independently, using all three methods, on the angiographic view that showed the most severe stenosis of the symptomatic carotid bifurcation. Interobserver agreement was determined, and 50 angiograms were remeasured to determine intraobserver agreement. There was little difference in the ability of the three methods to predict ipsilateral carotid distribution ischemic stroke. The CC method was consistently the most reproducible of the three, particularly for stenosis in the clinically important range of 50% to 90%. The CC method of measurement should be adopted as the standard method of measuring the degree of carotid stenosis on angiograms.

Background and Purpose— Fibrinogen is an independent risk factor for coronary events in population-based studies and in patients with coronary heart disease, but there is uncertainty about prediction of stroke, particularly in secondary prevention. Methods— We studied unpublished data from 3 prospective studies of patients with recent transient ischemic attack (TIA) or minor ischemic stroke: the United Kingdom TIA Aspirin (UK-TIA) trial (n=1860); the Dutch TIA trial (n=2960); and the Oxford TIA Study (n=293). By separate and pooled analysis, we used Cox models to determine the relationship between fibrinogen and risk of ischemic stroke and other vascular events during 23 272 patient-years of follow-up and adjusted for other risk factors. Results— There was no significant heterogeneity in fibrinogen risk associations between studies. Fibrinogen predicted subsequent ischemic stroke, with a pooled hazard ratio (HR) for values above the median of 1.34 (95% CI, 1.13 to 1.60; P =0.001). The association tended to be stronger in patients with nonlacunar (HR=1.42; 95% CI, 1.13 to 1.78; P =0.002) than lacunar syndromes (HR=1.09; 95% CI, 0.80 to 1.49; P =0.58), but was not significantly so ( P =0.18). There was no association with hemorrhagic stroke (adjusted HR=1.09; 95% CI, 0.55 to 2.17; P =0.81). Fibrinogen predicted acute coronary events (adjusted HR=1.42; 95% CI, 1.18 to 1.70; P P P =0.19). Conclusions— In patients with a previous TIA or ischemic stroke, risks of recurrent ischemic stroke and acute coronary events increase linearly with fibrinogen levels, but the relationships are weaker than in some previous population-based studies.

Background and Purpose Carotid endarterectomy reduces the risk of carotid territory ischemic stroke ipsilateral to a recently symptomatic severe carotid stenosis. However, the benefit is limited by the risks of stroke and death associated with the operation. Although reported surgical risks vary enormously, there has been no systematic review of the published literature. Methods We performed a systematic review of mortality and the risk of stroke and/or death due to endarterectomy for symptomatic carotid stenosis in studies published since 1980. Results Fifty-one studies fulfilled our criteria. Overall mortality was 1.62% (95% confidence interval [CI], 1.3 to 1.9), and the risk of stroke and/or death was 5.64% (95% CI, 4.4 to 6.9). However, there was significant heterogeneity of risk of stroke and/or death ( P Conclusions The reported risks of endarterectomy for symptomatic carotid stenosis show significantly greater variability than would be expected by chance. However, much of this variability can be accounted for by differences in methodology and authorship. The 5.6% overall risk of stroke and/or death is consistent with present guidelines.

Lacunar (small deep) and small centrum ovale infarcts (LACIs and SCOIs, respectively) are both small subcortical infarcts with the same appearance on computed tomography (CT), but they are located in

Objectives - The impact of stroke on the emotional outcome of patients is large. The aim was to describe the emotional outcomes among a cohort of patients which was of sufficient size to provide a precise estimate of their frequency and help identify those factors which are associated with poor outcomes after an acute stroke. Methods - 372 surviving patients, who had been referred to a hospital and entered into a randomised trial to evaluate a stroke family care worker, were asked to complete questionnaires at a 6 month follow up. These included measures of emotional distress (general health questionnaire 30 item, hospital anxiety and depression scale) and physical functioning (modified Rankin, Barthel index). A regression analysis was used to identify factors which were independently associated with poor outcomes. Results - 184 (60%) surviving patients scored more than 4 on the GHQ-30, 55 (22%) more than 8 on the HAD anxiety subscale, and 49 (20%) more than 8 on the HAD depression subscale. Patients with severe strokes resulting in physical disability were more likely to be depressed whereas there was a less strong relation between disability and anxiety. Patients with posterior circulation strokes had consistently better emotional outcomes than those with anterior circulation strokes. Conclusions - These data may help identify those patients at greatest risk of poor emotional outcomes and thus help in planning trials and delivering appropriate interventions.

Summary Background A winter excess of ischaemic stroke has been found in mortality and hospital-based studies. It is often assumed that this is due to seasonal variation in stroke incidence and several pathophysiological explanations have been proposed. We studied the incidence of stroke in relation to season and outside temperature. Methods The data came from a community-based study of first ever in a lifetime stroke in a defined population of about 105 000. 675 such strokes were registered over four years and the month of onset was analysed separately for cerebral infarction, primary intracerebral haemorrhage, and subarachnoid haemorrhage. Findings There was no significant seasonal variation. The incidence of primary intracerebral haemorrhage was increased at low temperatures, but there was no significant relation between the incidence of ischaemic stroke or subarachnoid haemorrhage and temperature. Interpretation The widely reported winter excess of ischaemic strokes may be an artifact due to referral bias in hospital-based studies and increased case fatality during the winter in mortality studies.

This chapter includes ten influential papers in the development of ideas about the causes and management of stroke. These are papers that have changed medical thinking or practice, or both simultaneously, and they cover the following topics: the carotid artery; angiography; carotid endarterectomy; embolism from the heart and atrial fibrillation; ruptured intracranial aneurysms recognized during life; intracranial venous thrombosis; thrombolysis in acute ischaemic stroke; and transient ischaemic attacks. The problematic issue of how to measure the severity of disease is addressed; and the history and development of specialist stroke units is also covered.

Carotid endarterectomy (CEA) is of benefit for stroke prevention in the presence of severe carotid stenosis, provided surgical morbidity and mortality are acceptably low. To assess the current performance of CEA in the UK, an interim analysis of 30-day postoperative outcome data, blinded to anaesthetic allocation, from the first 1,001 UK patients randomised in the GALA Trial (multicentre randomised trial of general versus local anaesthesia for CEA) took place and the time from last symptomatic event to surgery was recorded. The 30-day risk of stroke was 5.3%, myocardial infarction (MI) 0.4%, death 1.7%, and stroke, MI or death 6.4%. Median delay between symptoms and surgery was 82 days. These risks are similar to those reported in the large randomised trials of CEA, but current delays to surgery are excessive and must have substantially reduced the benefit of endarterectomy.

Sub-Saharan Africa is undergoing epidemiological transition. Stroke and other vascular diseases increasingly contribute to the burden of disease. There are no systematic reviews of stroke mortality, prevalence, incidence, and case fatality. We combined a thorough search and critical assessment of the published research. Stroke mortality is as high, perhaps higher, than in high-income regions and increases with age in sub-Saharan Africa as in high-income countries, but the absolute number of stroke deaths remains low. There are no adequate community-based stroke incidence studies. Hospital-based incidence is lower than in high-income regions, but higher in young people, possibly due to hospital admission bias. There are no community-based data on case fatality, but hospital-based case fatality is higher than elsewhere. The prevalence of stroke is lower than in high-income regions, but disabling stroke is as prevalent. As the region develops economically, the incidence of stroke and other vascular diseases will increase unless interventions are implemented. Only community-based incidence studies will accurately reveal the burden of stroke.

Here I have reviewed how good luck, bad luck and barriers determined my research directions in stroke over the last 30 or so years. Good luck should be exploited, and very often barriers can be not just overcome but put to good use as well. It is crucial for the young researcher to find mentors as good as I have had, and to move around to gain a broad experience, and for the experienced researchers to bring on the younger generation as I have tried to do.

A young man in his late teens presented with a four week history of malaise, vomiting, anorexia, and 7 kg weight loss. He was dehydrated and barium follow through revealed a band like obstruction of the 3rd and 4th parts of the duodenum. Following rehydration and normalisation of his biochemistry he had three generalised tonic-clonic seizures and was started on sodium valproate. This failed to control his seizures and phenytoin was added. He also experienced visual hallucinations, for instance seeing toilet seats being swallowed up. Laparotomy confirmed duodenal obstruction secondary to Wilkie’s syndrome (obstruction between the angle of the aorta and superior mesenteric artery, seen in association with weight loss). A duodeno-jejunal anastamosis was performed. Postoperatively his neurological condition deteriorated with increasing confusion, headache, and left sided myoclonus and weakness so he was transferred to the neurology service. The past medical history was revisited. He had had a normal birth and childhood milestones but he had always been thin and weak with reduced exercise tolerance compared to his two siblings. He had complained of intermittent abdominal pain and vomiting since the age of 5. He had no family history of neurological or gastrointestinal disease. It also turned out that he had been bitten by a tick three weeks before admission. On examination he was underweight at 40 kg with generalised muscle wasting and bilateral pes cavus. The most striking finding was epilepsia partialis continua (EPC) affecting the left arm and leg. He had a left homonymous hemianopia, dysarthria, and horizontal nystagmus on right gaze. In addition he had a left hemiparesis (MRC grade 2) and left sided sensory impairment (all modalities). Upper limb reflexes were normal but lower limb reflexes were absent. He had a very large number of investigations during the course of this admission and these are summarised …

Background and Purpose— Eligibility criteria determine the external validity (generalizability) of the results of randomized controlled trials. To increase the number of outcome events, and hence statistical power, some recent stroke prevention trials have required additional vascular risk factors for eligibility. Methods— To assess the merits of additional eligibility criteria in stroke prevention trials, we analyzed data from 3 trials and 1 hospital-referred series of patients with a transient ischemic attack or minor ischemic stroke. Patients were stratified according to 2 sets of additional risk factors similar to those used in recent trials (MATCH, SPORTIF and PRoFESS); risk of stroke, myocardial infarction, or vascular death was calculated in relation to the number of risk factors. Results— Although the observed risk during follow-up did increase with the number of risk factors present ( P Conclusions— The degree of patient selection introduced by use of additional vascular risk factors as eligibility criteria for trials can differ substantially between apparently similar sets of risk factors. Given that the potential for additional eligibility criteria to undermine generalizability and prolong recruitment outweighs any benefits in terms of statistical power, the exclusion of patients with no risk factors is difficult to justify.

Recent laws, and their interpretation, have made clinical research more difficult to do, and sometimes impossible. Furthermore the results of that research which can be done may even be unreliable. This is certainly against the public interest, and indeed the individual patient interest as well. But ethics committees have to abide by the law and so even though it is surely unethical to work against the public and individual interest that is exactly what ethics committees now have to endorse. The unintended consequences of the new regulations must be reduced by amending the law.

Background: Undernutrition is common in patients admitted with stroke. We aimed to establish whether the timing and route of enteral tube feeding after stroke affected patients' outcomes at 6 months. Methods: The FOOD trials consist of three pragmatic multicentre randomised controlled trials, two of which included dysphagic stroke patients. In one trial, patients enrolled within 7 days of admission were randomly allocated to early enteral tube feeding or no tube feeding for more than 7 days (early versus avoid). In the other, patients were allocated percutaneous endoscopic gastrostomy (PEG) or nasogastric feeding. The primary outcome was death or poor outcome at 6 months. Analysis was by intention to treat. Findings: Between Nov 1, 1996, and July 31, 2003, 859 patients were enrolled by 83 hospitals in 15 countries into the early versus avoid trial. Early tube feeding was associated with an absolute reduction in risk of death of 5.8% (95% CI -0.8 to 12.5, p=0.09) and a reduction in death or poor outcome of 1.2% (-4.2 to 6.6, p=0.7). In the PEG versus nasogastric tube trial, 321 patients were enrolled by 47 hospitals in 11 countries. PEG feeding was associated with an absolute increase in risk of death of 1.0% (-10.0 to 11.9, p=0.9) and an increased risk of death or poor outcome of 7.8% (0.0 to 15.5, p=0.05). Interpretation: Early tube feeding might reduce case fatality, but at the expense of increasing the proportion surviving with poor outcome. Our data do not support a policy of early initiation of PEG feeding in dysphagic stroke patients.

Clinical research is subject to increasing regulation by research ethics committees and research and development offices which are responding to social and political pressures, as well as to new legislation, both European and national, some of which is still being worked out. The resulting bureaucracy, expense and confusion are putting insuperable hurdles in the way of clinical research and clinical care is compromised. What research is still possible will only be done in large organisations and may even be seriously biased. The solutions are to inform and seek the help of the public and to forge alliances with patient groups. Patients have far more to lose than clinical researchers who, if clinically qualified, can more easily pursue a fulfilling career as clinicians rather than researchers.

If mine were merely a mild head injury, which it was according to Scottish Intercollegiate Guidelines Network guidelines,1 I dare not think what a moderate or severe head injury must feel like. In May 2010, I was on Richard Roberts’ new sailing boat, returning from our triumph in the Scottish Islands Peaks Race, which combines sailing 140 miles with three mountain marathons (fastest monohull, third overall, top of our class). We were about to enter the Crinan Canal, the short cut from the Clyde to the west coast. It was raining, slippery on deck and there were ropes lying about. Presumably I slipped or tripped, no one is sure, but I definitely fell head first into the cockpit, hitting the left side of my head and ear, and shoulder. I was completely unconscious for about a minute, much to Richard's consternation, who thought I was dead. I came round with a sore head, a bleeding cut behind my ear and pretraumatic amnesia of seconds, comfortably above the ceiling of 15 on the Glasgow Coma Scale (GCS). I was really not too bad, able to go down into the cabin, and with help get my waterproofs and boots off, and lie down on a bunk. Within an hour I was reading the newspaper and regretting whatever stupidity had caused the fall. My left ear was a mess, bruised and bleeding from the cut inflicted by my glasses. After motoring along the Crinan Canal for a couple of hours, we had another think. We did not need a neurologist, we had two already—me and Richard. In any event, UK neurologists know little if anything about head injury and even less about ear injury (alas, the recent “The Bare Essentials of Head Injury” in Practical Neurology was not in the ship's library). …

THE STORY In 2001, a retired seaman in his seventies presented with a progressive history of ear pain, deafness, double vision and facial weakness. Several months prior to this he had started to notice discomfort in his right ear and parotid area, with an aural discharge. Soon afterwards he noticed a similar pain in his left ear. He consulted an ear, nose and throat (ENT) surgeon who syringed both ears and drained a right middle ear effusion by inserting a grommet and performing a myringoplasty. A nasal polyp was removed at the same time. He received a two-week course of coamoxiclav. Despite these interventions, the pain worsened and he began to have difficulty hearing in both ears. Four months later he began to experience intermittent double vision and his hearing became worse. After a short course of oral steroids he developed left facial weakness. His ENT surgeon arranged a consultation

Thomas Willis was born in 1621, received his classical education and then medical degree from Oxford in 1646, became a highly successful and prosperous physician, and, in 1660, was appointed Professor of Natural Philosophy at the University of Oxford.1 Although at that time there were no neurologists as such, he coined the word neurology in his Cerebri Anatome :2 “We should deliver an exact neurology, or doctrine of the nerves” and “without the perfect knowledge of the nerves the doctrine of the brain and its appendix would be left wholly lame and imperfect.” Of course, his pharmacopoeia was primitive in the extreme and he had no reliable way of proving that any treatment interventions worked, unless they had a very obvious and immediate effect. But these days we have the most remarkable tool to evaluate our interventions, the randomized controlled trial, although it is not yet 60 years since the first trial in the modern era was published in the BMJ on October 30, 1948, of streptomycin for pulmonary tuberculosis3 (Figure 1). It was conducted in the UK just after World War II when the supply of the antibiotic was so limited that Austin Bradford Hill, the statistician, was able to persuade clinicians to use randomization between the new treatment and control as a form of fair rationing and to construct 2 groups of patients who were so similar in their prognosis at baseline that any definite difference in their outcome must be because of the new treatment. Figure 1. The title page of the trial of streptomycin from BMJ in 1948 (with permission). And in the past 3 decades we have had another tool, meta-analysis, largely developed in Oxford by Richard Peto the statistician and Iain Chalmers who devised the Cochrane Library, and in the US …

Background and Purpose— The importance of stroke in low-income regions such as sub-Saharan Africa has recently been emphasized. However, little is known about the burden of stroke in sub-Saharan Africa. We investigated the prevalence of stroke survivors in the Agincourt Health and Population Unit, a demographic surveillance site in the rural northeast of South Africa. Methods— Census workers asked household informants 2 screening questions for stroke during the annual census. If either question was answered positively, a clinician visited individuals aged ≥15 years to confirm the likely diagnosis of stroke. We performed a detailed assessment and defined stroke according to the World Health Organization criteria. Results— A total of 42 378 individuals were aged ≥15 years. There were 982 positive responses to the questionnaire, and we examined 724 individuals (74%). We identified 103 strokes (crude prevalence, 243/100 000). After adjustment for those we did not examine, the prevalence was 300/100 000 (95% CI, 250 to 357). Sixty-six percent of stroke survivors needed help with at least 1 activity of daily living (Segi age-standardized prevalence, 200/100 000). Conclusions— Stroke prevalence in rural South Africa is higher than previously documented in Africa but lower than in high-income countries. However, the prevalence of stroke survivors requiring help with at least 1 activity of daily living is already at high-income country levels. South Africa suffers from a huge burden of HIV/AIDS and diseases of poverty and violence and now faces the challenge of adapting its health systems to face the coming epidemic of vascular disease.

Background: There are numerous terms to describe seizure-like episodes not explained by disease—for example pseudoseizures, psychogenic seizures and non-epileptic attack disorder. Debates about which is best to use tend to centre around theoretical arguments and not scientific evaluation. In this study we examine the meanings of these labels for patients, which have the least potential to offend, and consequently to provide a more positive basis for further management. Methods and results: We interviewed 102 consecutive general neurology outpatients who were asked to consider a scenario that they were being given a diagnosis by a doctor after experiencing a blackout with normal tests. We investigated 10 different diagnoses for blackouts with six different connotations. Three of these connotations—‘putting it on', ‘mad' and ‘imagining symptoms'—were used to derive an overall ‘offence score'. Using this score some labels were highly offensive, e.g. ‘symptoms all in the mind' (89%) and ‘hysterical seizures' (48%). There were no significant differences between the labels ‘pseudoseizures', ‘psychogenic seizures' and ‘non-epileptic attack disorder'. ‘Stress-related seizures' and ‘functional seizures' were significantly less offensive than these three diagnoses and were equivalent to ‘tonic–clonic' and ‘grand mal'. Conclusions: Many labels for seizures unexplained by disease are potentially offensive to patients. The search for labels that accurately describe the phenomenon, can be used by patients, doctors and researchers and enhance trust and recovery is worthwhile and amenable to scientific study.

Stroke is a major public-health burden worldwide. Prevention programmes are essential to reduce the incidence of stroke and to prevent the all but inevitable stroke epidemic, which will hit less developed countries particularly hard as their populations age and adopt lifestyles of the more developed countries. Efficient, effective, and rapid diagnosis of stroke and transient ischaemic attack is crucial. The diagnosis of the exact type and cause of stroke, which requires brain imaging as well as traditional clinical skills, is also important when it will influence management. The treatment of acute stroke, the prevention and management of the many complications of stroke, and the prevention of recurrent stroke and other serious vascular events are all improving rapidly. However, stroke management will only be most effective when delivered in the context of an organised, expert, educated, and enthusiastic stroke service that can react quickly to the needs of patients at all stages from onset to recovery.

BACKGROUND: Endarterectomy reduces risk of stroke in certain patients with recently symptomatic internal carotid stenosis. However, investigators have made different recommendations about the degree of stenosis above which surgery is effective, partly because of differences between trials in the methods of measurement of stenosis. To accurately assess the overall effect of surgery, and to increase power for secondary analyses, we pooled trial data and reassessed carotid angiograms. METHODS: We pooled data from the European Carotid Surgery Trial (ECST), North American Symptomatic Carotid Endarterectomy Trial, and Veterans Affairs trial 309 from the original electronic data files. Outcome events were re-defined, if necessary, to achieve comparability. Pre-randomisation carotid angiograms from ECST were re-measured by the method used in the other two trials. RESULTS: Risks of main outcomes in both treatment groups and effects of surgery did not differ between trials. Data for 6092 patients, with 35000 patient-years of follow-up, were therefore pooled. Surgery increased the 5-year risk of ipsilateral ischaemic stroke in patients with less than 30% stenosis (n=1746, absolute risk reduction -2.2%, p=0.05), had no effect in patients with 30-49% stenosis (1429, 3.2%, p=0.6), was of marginal benefit in those with 50-69% stenosis (1549, 4.6%, p=0.04), and was highly beneficial in those with 70% stenosis or greater without near-occlusion (1095, 16.0%, p

Background and Purpose— Carotid endarterectomy (CEA) reduces the risk of stroke ipsilateral to recently symptomatic severe carotid stenosis. Other techniques such as percutaneous transluminal angioplasty with stenting are currently being compared with CEA. Thus far, case series and several small, randomized, controlled trials of CEA versus percutaneous transluminal angioplasty (with and without stenting) have focused primarily on the 30-day procedural risks of stroke and death. However, long-term durability is also important. To determine the long-term risk of stroke after CEA and to identify risk factors, we studied patients in the European Carotid Study Trial (ECST), the largest published cohort with long-term follow-up by physicians after CEA. Methods— Risks of ipsilateral carotid territory ischemic stroke were calculated by Kaplan-Meier analysis starting on the 30th day after CEA in 1728 patients who underwent trial surgery. Risk factors were determined by Cox regression. For comparison, we also determined the “background” risk of stroke on medical treatment in the ECST in the territory of 558 previously asymptomatic contralateral carotid arteries with Results— The risks of disabling ipsilateral ischemic stroke and any ipsilateral ischemic stroke were constant after CEA, reaching 4.4% [95% confidence interval (CI), 3.0 to 5.8] and 9.7% (95% CI, 7.6 to 11.7), respectively, by 10 years. The equivalent ischemic stroke risks distal to contralateral Conclusions— Although the risk of late ipsilateral ischemic stroke after CEA for symptomatic stenosis is approximately double the background risk in the territory of

In the UK, most patients admitted to hospital with acute neurological problems are not looked after or even seen by a consultant neurologist. As a result, the outcome of their care may be suboptimal. The Association of British Neurologists believes that, in order to provide a reasonable service, the number of consultant neurologists will have to increase more than threefold, to about 1,400. This should be achievable in the next 10-15 years and would bring UK neurological services up to the standards that already obtain in comparable European countries.

Introduction: Small primary intracerebral haemorrhages (PICHs) cause mild stroke symptoms and resolve rapidly on CT. Delays in imaging in stroke incidence studies may therefore have inadvertently led to an underestimate of the frequency of small PICHs. Objective: To determine whether the rate and timing of CT in community-based stroke incidence studies was adequate to determine accurately the proportion of strokes due to PICH. Methods: A systematic review of community-based stroke incidence studies that included details on pathological type of stroke, excluding subarachnoid haemorrhage. We extracted information on the proportions of patients scanned, the timing of scans, characteristics of patients that were less likely to be scanned, and the proportion of ischaemic, or haemorrhagic, or unknown strokes. Results: In the 25 studies identified, scanning methods were poorly documented. When mentioned, the median proportion of patients scanned was 63 % (95 % confidence intervals (CI) 60 to 85 %) and mostly performed outside the time for reliable distinction of PICH from ischaemic stroke (median 18.5 days, 95 % CI 7 to 30 days). Patients particularly likely to miss scanning were older, those not admitted to hospital or who died early after stroke. Conclusion: The scanning strategy documentation, the proportion of patients scanned and the timing of scanning in stroke incidence studies has been suboptimal. The frequency of a primary intracerebral haemorrhage, and its distribution in different age groups of patients or severities of stroke, has been underestimated. Future incidence studies should adopt more rigorous scanning policies and describe these policies more precisely.

BACKGROUND AND PURPOSE Previous studies of transcranial Doppler (TCD) sonography in acute stroke have used the relative difference between the symptomatic and asymptomatic arteries to assess arterial occlusion. However, a simple measure of absolute mean flow velocity might provide a direct assessment of "perfusion reserve" in acute ischemic stroke. METHODS In a prospective study, 62 patients with ischemic stroke had TCD and a mean cerebral transit time examination within 48 hours of stroke. Absolute intracranial arterial mean flow velocities were correlated with the corresponding absolute mean transit times. RESULTS The authors found a significant correlation between middle cerebral artery (MCA) mean flow velocity and transit time in the symptomatic (Spearman rank correlation coefficient [rho] = -0.65, P < .01) but not in the asymptomatic (rho = -0.04, P = ns) MCA territory. Equations relating absolute mean flow velocity to absolute transit time were derived. CONCLUSION The findings suggest that in the normal hemisphere (with intact autoregulation on the horizontal portion of the autoregulation curve), flow velocity and transit time are not closely related to each other, but in the symptomatic hemisphere (on the downward slope of the autoregulation curve), flow velocity is directly proportional to the transit time and, therefore, to its inverse, perfusion reserve. The use of absolute mean flow velocity values on TCD should be further explored as a simple way of assessing "perfusion" in acute ischemic stroke.

Objectives Lacunar infarcts are thought to be mostly due to intracranial small vessel disease. Therefore, when a stroke patient with a relevant lacunar infarct does have severe ipsilateral internal carotid artery (ICA) or middle cerebral artery (MCA) disease, it is unclear whether the arterial disease is causative or coincidental. If causative, we would expect ICA/MCA disease to be more severe on the symptomatic side than on the asymptomatic side. Therefore, our aim was to compare the severity of ipsilateral with contralateral ICA and MCA disease in patients with lacunar ischaemic stroke. Methods We studied 259 inpatients and outpatients with a recent lacunar ischaemic stroke and no other prior stroke. We used carotid Duplex ultrasound and transcranial Doppler (TCD) ultrasound to identify ICA and MCA disease, and compared our results with previously published data. Results In our study, there was no difference between the severity of ipsilateral and contralateral ICA stenosis within individuals (median difference 0 %, Wilcoxon paired data p=0.24, comparing severity of ipsilateral and contralateral stenosis). The overall prevalence of severe ipsilateral stenosis was 5 %, and the prevalence of severe contralateral stenosis was 4 % (OR 1.6, 95 % CI 0.6, 4.8). There was no difference in the prevalence of ipsilateral and contralateral MCA disease. A systematic review of the other available studies strengthened this conclusion. Conclusion Carotid stenosis in patients with a lacunar ischaemic stroke may be coincidental. Further studies are required to elucidate the causes of lacunar stroke, and to evaluate the role of carotid endarterectomy.

Background and Purpose— Carotid endarterectomy (CEA) reduces the risk of stroke in patients with severe stenosis of the internal carotid artery. However, the cost implications of this procedure have not yet been satisfactorily addressed. The objective of this systematic review was to critically appraise the studies addressing the economic implications of CEA and the associated preoperative arterial imaging. Methods— A systematic search strategy was developed to identify research articles related to the economic evaluation of CEA and the associated preoperative imaging. MEDLINE, EMBASE, and BIOSIS were electronically searched, and reference lists from identified studies were searched manually. Methods used to critically appraise these studies followed proposed guidelines for an economic evaluation that addresses 10 distinct aspects under 3 separate headings. Results— Studies identified were either partial economic or full economic evaluations, with the majority coming from the United States. The methodological quality seems to have improved over time. The studies that assessed cost-effectiveness of CEA were all modeling studies; although the same baseline parameters were used, divergent conclusions were reached. Variation in the cost estimates of CEA ($9500 to $11 500) in the same health care system was also observed in the studies reporting only on the cost of carotid surgery. For a symptomatic patient, the benefit of CEA ranged from 0.35 quality adjusted life years (QALYs) (4.2 months) at a cost of $4100 per QALY to 0.93 QALYs (11.2 months) at a cost of $434 per QALY. For an asymptomatic patient, the cost-effectiveness of CEA varied from 0.15 QALYs (1.8 months) at a cost of $52 700 per QALY to 0.25 QALYs (3 months) at a cost of $8004 per QALY. Conclusions— Divergent conclusions of the cost-effectiveness of CEA were reported from studies that addressed the same questions and using similar parameters in their models. The cost estimates of the procedure and the different time periods used in the studies might explain these inconsistencies. Modeling studies in hypothetical cohorts might also be to blame. The cost-effectiveness of CEA will only definitively be assessed when real patient data are used.

Background and Purpose — The cost of carotid endarterectomy (CEA) usually considers only the cost of the preoperative investigations and the procedure for the individual patient but ignores the cost incurred in selecting a patient from a referred “pool” of potential candidates or the “total direct program cost.” The aim of this study was to estimate the total direct program cost (workup and procedure) of CEA in a large major teaching hospital in Edinburgh, Scotland using a retrospective study design. Methods — Participants were patients with transient ischemic attacks and mild strokes referred to the neurovascular clinics for assessment, investigation, and possible CEA. The “workup” was defined as the clinical consultation, carotid duplex, 1 follow-up visit, and a catheter angiogram where indicated. We used data routinely collected from the neurovascular clinics during a 1-year period to estimate the workup cost of patients who might be suitable for CEA. The CEA procedure cost was estimated prospectively in a concurrent study. Estimated costs were applied to the proportions assessed at the different levels of investigation to determine the total direct program cost of CEA. Results — A total of 790 new patients with symptoms suggestive of transient ischemic attacks and mild strokes were identified. Four hundred one (51%) patients were referred for carotid duplex. Duplex identified 78 (10%) with carotid stenosis of ≥70%. Of the total of 790 patients, 26 (3.3%) had catheter angiogram and 18 (2.3%) had CEA. The total direct program cost to investigate this cohort was about £207 000, with 68% (£140 000) of the cost incurred before any surgery was performed. Conclusion — The cost of identifying suitable patients for carotid surgery is quite high, with more than 30% of the cost attributed to the initial consultation at the neurovascular clinics. The cost of preventing 1 stroke by CEA is in the region of £100 000 at 1997/1998 prices if all the costs incurred in the workup of a cohort for potential CEA are included.

CASE PRESENTATION History In early 1999, a right-handed manufacturing engineer in his thirties presented to his general practitioner (GP) with a week-long history of diminished sensation and paraesthesiae affecting his left arm and leg. Two months prior to presentation he had contracted a ‘flu-like illness that had left him with persistent fatigue. At presentation, his GP noticed weakness of his left hand and made a presumptive diagnosis of multiple sclerosis. He prescribed a five-day course of oral prednisolone 40 mg daily, which the patient took for only one day, making a transient improvement. The next day he had difficulty making decisions at work and was stopped by the police for speeding in a residential area. Two weeks after the onset of his neurological symptoms, he was admitted to a local hospital with confusion and then transferred to the Neurology department in Edinburgh the following day. Two years beforehand, in 1997

Objectives: carotid endarterectomy is associated with significant morbidity and mortality. A better understanding of the relationships between baseline characteristics and outcome may help to reduce the risks of surgery. In order to make accurate and unbiased estimates of surgical risk it is important to study cohorts of patients that were established prospectively, where independent physicians assessed outcome, and where the decision to analyse and report the results was not data-dependent. The surgical arm of the European Carotid Surgery Trial (ECST) is such a cohort. Methods: the 30-day outcome of carotid endarterectomy was analysed in ECST surgery patients in relation to their baseline clinical and angiographic characteristics. The severity of operative strokes was compared with that of strokes that occurred in the medical group.Results : 1729 patients underwent trial surgery. There were 17 deaths (1.0%, 95% CI=0.6–1.6) and 105 non-fatal major strokes (6.1%, 95% CI=5.0–7.3) within 30 days of surgery. The risk of major stroke or death was 7.1% (95% CI=5.9–8.4). The risk of disabling or fatal stroke was 3.0% (95% CI=2.1–3.8). The ratio of disabling to non-disabling operative strokes was similar to that in the medical group. Several baseline characteristics predicted the operative risk of stroke and death in univariate analyses, but only four were independent risk factors in a multiple regression analysis: presentation with cerebral TIA vs ocular ischaemic events only (HR=2.99, 95% CI=1.33–6.69, p=0.008); female sex (HR=2.04, 95% CI=1.37–3.06, p=0.001); systolic hypertension (HR=1.01 per 10 mmHg, 95% CI=1.00–1.02, p=0.03) and peripheral vascular disease (HR=2.17, 95% CI=1.17–2.89, p=0.001). Conclusions: the operative risk of stroke and death in the ECST was comparable with other prospective studies and trials in which patients were assessed postoperatively by both a physician and a surgeon. Case fatality and disability after operative stroke are similar to strokes that occur on medical treatment only. Several baseline patient characteristics predict surgical risk and it may be possible to use these characteristics to aid patient selection and surgical audit.

Large trials provide more precise estimates of treatment effects than small trial (how good is the treatment?) and they may allow a few sensible and pre-defined sub-group analyses (for whom does the treatment work best?). But large trials will not get done unless they are simple and as part of normal clinical practice as possible.

A 59 year old, retired metal worker presented with a 3 month history of difficulty walking. He had initially developed left leg weakness, followed 1 month later by numbness of both legs, a burning sensation in his anal region and penis, constipation, urinary frequency, retention, and incontinence. At that stage he presented to another hospital with abdominal pain, but all investigations for this were normal. On examination there was some weakness of his left leg, but no objective sensory loss in the legs or perineum. The weakness progressed to involve his right leg over the next 2 months such that he needed a stick to walk. For 6 years before presentation he had had unremitting paraesthesiae of both shins, for which no cause had been found. He had been judged unfit to work 4 years previously due to depression. Ankylosing spondylitis had been diagnosed at the age of 30, followed by proctitis 10 years later for which he had been successfully treated with sulphasalazine. Cognitive, cranial nerve, cerebellar, and general physical examination were unremarkable. Upper arm and pectoralis muscles were atrophied, but not weak. His gait was broad based, stiff, and he dragged both feet. There was bilateral MRC grade 4 weakness of knee flexion and MRC grade 4+ weakness of the left extensor hallucis longus muscle. Jaw jerk was absent, but deep tendon reflexes in the arms and legs were brisk with clonus at the right ankle, an absent left ankle jerk, and up going plantar responses. Pain and touch sensations were diminished over both forearms, as they were below both knees with additional impairment of vibration sense. Initial abnormal investigations were C reactive protein 43.7 mg/l (reference range (RR) 0–8 mg/l), lactate dehydrogenase 638 μmol/l (RR 300–620 μmol/l), serum angiotensin converting enzyme (SACE) 28 U/l (RR 8–21 U/l) …

“O my! O my! O my!” exclaimed Mole to the water Rat when he saw the beauties of the river in early spring in the first chapter of Wind in the Willows , a book that many children in the UK were, and are still, brought up on. “O my! O my! O my!” I thought as the letters of concern and complaint came flooding in after Chris Hawkes's editorial ‘I’ve stopped examining patients!'.1 More letters than after almost all previous articles combined (look at them after his article on line). Why? I think essentially because he struck at the heart of a neurologist's prowess—the ability to elegantly, accurately and quickly elicit physical signs which lesser mortals (ie, general internal physicians) have missed or never heard of. And then to use the signs, along with the history, to direct appropriate investigations, if any at all are required, and so make a diagnosis. Examining the nervous system is what we are trained to do, over and over again. And in our turn we relentlessly teach the students to ‘examine the nervous system!’. Indeed we endlessly debate among ourselves the best way to reinforce the reflexes, look for nystagmus and so on. Professor Hawkes exaggerates for effect but even he still admits to examining some patients under some circumstances. I agree. In every single case we should ask ourselves the question “exactly why am I trying to elicit this particular physical sign in this particular patient?” After all, there is an opportunity cost in a busy clinic where time spent talking to the patient could be compromised by too much fiddling with their toes. I well recall being reprimanded by a senior neurosurgeon in an x-ray meeting when I remarked that it was pointless doing the plantar responses because I already …