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Sickle cell disease (SCD) is the most common type of hereditary anaemia and genetic disorder worldwide. Cerebrovascular disease is one of its most devastating complications, with consequent increased morbidity and mortality. Current guidelines suggest that children and adults with SCD who develop acute ischaemic stroke should be transfused without delay. Those with acute ischaemic stroke aged over 18 years who present within 4.5 hours of symptom onset should be considered for intravenous thrombolysis; older patients with conventional vascular risk factors are the most likely to benefit. Endovascular thrombectomy should be considered carefully in adults with SCD as there are few data to guide how the prevalence of cerebral vasculopathy may confound the expected benefits or risks of intervention. We present a practical approach to cerebrovascular disease in sickle cell patients based on the available evidence and our experience.

Spontaneous spinal cord infarction is significantly less common than cerebrovascular disease. Because of the tight anatomical distribution of pathways in the cord, small spinal cord infarcts usually give more obvious symptoms and signs than similar lesions in the brain. Large epidemiological stroke studies have generally not included spinal cord stroke and so the incidence of vascular syndromes in the spinal cord is unknown. Management and prevention strategies for spontaneous spinal cord infarcts stem from small case series and case reports. Patient outcomes from spinal cord infarction are better with prompt recognition, timely management and prevention of associated medical complications arising from paraplegia, tetraplegia, neurogenic bladder and bowel dysfunction. The process of rehabilitation following spinal cord infarction is an evolving area.

Cerebral small vessel disease (SVD) causes lacunar stroke and vascular cognitive impairment in older people. The pathogenic pathways from vessel pathology to parenchymal damage in SVD are unknown. Neurofilaments are axonal structural proteins. Neurofilament-light (NfL) is an emerging biomarker for neurological disease. Here, we examined the high molecular weight form neurofilament-heavy (NfH) and quantified a characteristic pattern of peri-arterial (vasculocentric) NfH labeling. Subcortical frontal and parietal white matter from young adult controls, aged controls, and older people with SVD or severe Alzheimer disease (n = 52) was immunohistochemically labeled for hyperphosphorylated NfH (pNfH). The extent of pNfH immunolabeling and the degree of vasculocentric axonal pNfH were quantified. Axonal pNfH immunolabeling was sparse in young adults but a common finding in older persons (controls, SVD, or AD). Axonal pNfH was often markedly concentrated around small penetrating arteries. This vasculocentric feature was more common in older people with SVD than in those with severe AD (p = 0.004). We conclude that axonal pNfH is a feature of subcortical white matter in aged brains. Vasculocentric axonal pNfH is a novel parenchymal lesion that is co-located with SVD arteriopathy and could be a consequence of vessel pathology.

Cerebral small vessel disease (SVD) is common in older people and is associated with lacunar stroke, white matter hyperintensities (WMH) and vascular cognitive impairment. Cerebral blood flow (CBF) is reduced in SVD, particularly within white matter.Here we quantified test–retest reliability in CBF measurements using pseudo-continuous arterial spin labelling (pCASL) in older adults with clinical and radiological evidence of SVD (N=54, mean (SD): 66.9 (8.7) years, 15 females/39 males). We generated whole-brain CBF maps on two visits at least 7 days apart (mean (SD): 20 (19), range 7-117 days).Test–retest reliability for CBF was high in all tissue types, with intra-class correlation coefficient [95%CI]: 0.758 [0.616, 0.852] for whole brain, 0.842 [0.743, 0.905] for total grey matter, 0.771 [0.636, 0.861] for deep grey matter (caudate-putamen and thalamus), 0.872 [0.790, 0.923] for normal-appearing white matter (NAWM) and 0.780 [0.650, 0.866] for WMH (all pWe conclude that pCASL has high test–retest reliability as a quantitative measure of CBF in older adults with SVD. These findings support the use of pCASL in routine clinical imaging and as a clinical trial endpoint.All data come from the PASTIS trial, prospectively registered at: https://eudract.ema.europa.eu (2015-001235-20, registered 13/05/2015), http://www.clinicaltrials.gov (NCT02450253, registered 21/05/2015).

Strokectomy means surgical excision of infarcted brain tissue post-stroke with preservation of skull integrity, distinguishing it from decompressive hemicraniectomy. Both can mitigate malignant middle cerebral artery (MCA) syndrome but evidence regarding strokectomy is sparse. Here, we report our data and meta-analysis of strokectomy compared to hemicraniectomy for malignant MCA infarction. All malignant MCA stroke cases requiring surgical intervention in a large tertiary centre (January 2012–December 2017,N = 24) were analysed for craniotomy diameter, complications, length of follow-up and outcome measured using the modified Rankin score (mRS). Good outcome was defined as mRS 0–3 at 12 months. In a meta-analysis, outcome from strokectomy (pooled from our cohort and published strokectomy studies) was compared with hemicraniectomy (our cohort pooled with published DECIMAL, DESTINY and HAMLET clinical trial data). In our series (N = 24, 12/12 F/M; mean age: 45.83 ± 8.91, range 29–63 years), 4 patients underwent strokectomy (SC) and 20 hemicraniectomy (HC). Among SC patients, craniotomy diameter was smaller, relative to HC patients (86 ± 13.10 mm, 120 ± 4.10 mm, respectively;p = 0.003), complications were less common (25%, 55%) and poor outcomes were less common (25%, 70%). In the pooled data (N = 41 SC, 71 HC), strokectomy tended towards good outcome more than hemicraniectomy (OR 2.2, 95% CI 0.99–4.7;p = 0.051). In conclusion, strokectomy may be non-inferior, lower risk and cost saving relative to hemicraniectomy sufficiently to be worthy of further investigation and maybe a randomised trial.

Patent foramen ovale (PFO) is the most common anatomical cause of an interatrial shunt. It is usually asymptomatic but may cause paradoxical embolism, manifesting as stroke, myocardial infarction or visceral/peripheral ischaemia. PFO is a risk factor for stroke and may be associated with migraine with aura. New evidence suggests PFO closure reduces the risk of recurrent ischaemic stroke in a highly selected population of stroke survivors: those aged 60 years or younger with a cryptogenic stroke syndrome, a large right-to-left shunt, an atrial septal aneurysm and no evidence of atrial fibrillation. They benefit from percutaneous PFO closure in addition to antiplatelet therapy, rather than antiplatelet therapy alone. Current evidence does not support PFO closure in the treatment of migraine.

Introduction\ud There are few randomized clinical trials in vascular cognitive impairment (VCI). This trial tested the hypothesis that the PDE5 inhibitor tadalafil, a widely used vasodilator, increases cerebral blood flow (CBF) in older people with symptomatic small vessel disease, the main cause of VCI.\ud \ud Methods\ud In a double-blind, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥7 days apart (randomized to order of treatment). The primary endpoint, change in subcortical CBF, was measured by arterial spin labelling.\ud \ud Results\ud Tadalafil increased CBF non-significantly in all subcortical areas (N = 55, age: 66.8 (8.6) years) with greatest treatment effect within white matter hyperintensities (+9.8%, P = .0960). There were incidental treatment effects on systolic and diastolic blood pressure (–7.8, –4.9 mmHg; P < .001). No serious adverse events were observed.\ud \ud Discussion\ud This trial did not identify a significant treatment effect of single-administration tadalafil on subcortical CBF. To detect treatment effects may require different dosing regimens.

Introduction: Risk factors for neurological complications in sickle cell disease differ in the adult and pediatric populations. Here, we focused on neurological complications in adults with sickle cell disease.Methods: Patients were selected using the audit data from the St George's Hospital Red Cell Database. The genotyping, demographics, clinical data, and investigation findings were collected.Results: A total of 303 patients were enrolled in the study: hemoglobin S homozygosity (HbSS) genotype 56%, hemoglobin S and C coinheritance (HbSC) genotype 35%, and hemoglobin S and β-thalassemia coinheritance (HbSβ) thalassemia genotype 9%; the mean age was 38.8 years (±13.5 SD) with 46% males. The most common neurological complication was cerebrovascular disease (n = 37, 12%) including those with ischemic stroke (10%), cerebral vasculopathy (3%), and intracranial hemorrhage (1%). Ischemic stroke was common among the HbSS genotype compared with other genotypes (8 vs. 1.6%, p = 0.001). Comparing the patients with sickle cell disease who had suffered a stroke to those who had not, there was a higher proportion of intracranial vasculopathy (p = 0.001, in particular, Moyamoya) and cognitive dysfunction (p < 0.0001).Conclusion: Our cohort supports previous reports that the most common neurological complication in adult sickle cell patients is cerebrovascular disease. Strategies to prevent cerebral vasculopathy and cognitive impairment should be explored.

There is no consensus on how to structure and deliver neurology training. The General Medical Council’s annual National Training Survey indicates that the quality of UK neurology training is very variable, but does not explain this variation. We used the survey data to identify the four highest and lowest performing sites for neurology training across the UK. We conducted semistructured interviews with groups of local trainees and, separately, local trainers in an exploratory qualitative study, and identified common themes across a range of aspects of neurology training. Here we present our findings, share case studies from top-performing sites and make recommendations on how best to train a neurologist.

Background and Purpose: Spontaneous intracerebral hemorrhage (sICH) is a common form of hemorrhagic stroke, with high mortality and morbidity. Pathophysiological mechanisms in sICH are poorly understood and treatments limited. Neuroinflammation driven by microglial-macrophage activation contributes to brain damage post-sICH. We aim to test the hypothesis that an anti-inflammatory (repair) process occurs in parallel with neuroinflammation in clinical sICH. Methods: We performed quantitative analysis of immunohistochemical markers for microglia and macrophages (Iba1, CD68, TMEM119, CD163, and CD206) in brain tissue biospecimens 1 to 12 days post-sICH and matched control cases. In a parallel, prospective group of patients, we assayed circulating inflammatory markers (CRP [C-reactive protein], total white cell, and monocyte count) over 1 to 12 days following sICH. Results: In 27 supratentorial sICH cases (n=27, median [interquartile range] age: 59 [52–80.5], 14F/13M) all microglia-macrophage markers increased post-sICH, relative to control brains. Anti-inflammatory markers (CD163 and CD206) were elevated alongside proinflammatory markers (CD68 and TMEM119). CD163 increased progressively post-sICH (15.0-fold increase at 7–12 days, P P P =0.020) then declined at 7 to 12 days. Monocytes increased from 0 to 2 to 3 to 5 days (1.8-fold, P Conclusions: An anti-inflammatory pathway, enlisting native microglia and blood monocytes, occurs alongside neuroinflammation post-sICH. This novel pathway offers therapeutic targets and a window of opportunity (3–5 days post-sICH) for delivery of therapeutics via invading monocytes.

Intravenous thrombolysis with alteplase within 4.5 hours from symptom onset is a well-established treatment of acute ischaemic stroke (AIS). The aim was to compare alteplase for AIS between patients aged >80 and ≤80 years in our registry data, from 2013 to 2018. Mechanical thrombectomy cases were excluded. We assessed clinical outcomes over the six-year period and between patients aged over 80 and ≤80 years, using measures including the discharge modified Rankin Scale (mRS), 24-hour National Institutes of Health Stroke Scale (NIHSS) improvement, and symptomatic intracerebral haemorrhage (sICH) rate. Of a total of 805 AIS patients who received intravenous alteplase, 278 (34.5%) were over 80 years old, and 527 (65%) were younger. 616 (76.5%) received thrombolysis ≤ 3 hours after symptom onset and 189 (23.5%) within 3-4.5 hours. Median baseline mRS and NIHSS of the elderly cohort were 1 (IQR 0-5) and 13 (IQR 2-37), respectively, compared to the younger cohort 0 (IQR 0-5) and 9 (IQR 0-29). The sICH rate was 7.2% in the elderly and 4.6% in those ≤80 years, p = 0.05 . NIHSS improved within 24 hours in 34% of the elderly cohort compared to 35% in the younger cohort. At hospital discharge, the mortality rate was 9% in the elderly cohort compared to the 6% in the younger cohort, p = 0.154 . 25% of patients aged >80 years had mRS ≤ 2 compared to 47% in the younger patients ( p < 0.0001 ). In conclusion, thrombolysis in elderly patients results in clinical improvement comparable to younger patients.

Introduction\ud Radiolabeled ligands for fibrillar amyloid beta (Aβ) peptides are used in positron emission tomography (PET) for dementia diagnosis. Current ligands do not discriminate parenchymal amyloid plaques from cerebral amyloid angiopathy (CAA).\ud \ud Methods\ud We undertook neuropathological examination of 65 older people (81.6 ± 7.96 (mean ± SD) years, 27F/38M): 15 with neuropathological diagnosis of AD, 25 with neuropathological diagnosis of other neurodegenerative dementias (Lewy body dementia and Parkinson disease dementia), and 25 without significant neurodegenerative pathology.\ud \ud Results\ud We observed CAA in non‐Alzheimer's dementia (non‐AD dementia) and control brains, of comparable extent to those with neuropathologically confirmed AD. Aβ‐positive vessel density did not differ significantly between non‐AD dementia and control groups. Across all subjects there was a highly significant correlation between vessel Aβ40 density and vessel Aβ42 density (Spearman rho = 0.855, P < .001). CAA was absent or sparse in subcortical white matter across all patient groups.\ud \ud Conclusion\ud Our data indicate that CAA can be abundant in non‐AD brains and raise a cautionary note regarding interpretation of amyloid PET imaging.

Cerebral small vessel disease in deep penetrating arteries is a major cause of lacunar infarcts, white matter lesions and vascular cognitive impairment. Local cerebral blood flow in these small vessels is controlled by endothelial-derived nitric oxide, which exerts a primary vasodilator stimulus on vascular myocytes, via cytoplasmic cyclic GMP. Here, we investigated whether the cGMP-degrading enzyme phosphodiesterase-5 (PDE5) is present in small penetrating arteries in the deep subcortical white matter of older people. Frontal cortical tissue blocks were examined from donated brains of older people (n = 42, 24 male: 18 female, median age 81, range: 59-100 years). PDE5, detected by immunohistochemical labeling, was graded as absent, sparse, or abundant in vascular cells within small arteries in subcortical white matter (vessel outer diameter: 20-100 µm). PDE5 labeling within arterial myocytes was detected in all cases. Degree of PDE5 expression (absent, sparse, or abundant) was not associated with age or with neuropathological diagnosis of small vessel disease. In conclusion, PDE5 is present in vascular myocytes within small penetrating arteries in older people. This is a potential molecular target for pharmacological interventions.

Recombinant tissue plasminogen activator (rtPA) is currently the only approved thrombolytic agent for treating acute ischaemic stroke that is widely used in clinical practice. However, it may cause haemorrhage and hypersensitivity reactions. Orolingual angioedema is an infrequent, usually mild but potentially life threatening, hypersensitivity reaction to rtPA. Our understanding of the basic biology of angioedema has increased in recent years. There is growing evidence that rtPA-induced orolingual angioedema is driven mainly by bradykinin generation rather than it being an anaphylactic response. Monitoring is important because orolingual angioedema may evolve and compromise airways and a small number do have angioedema as part of systemic anaphylaxis. There are no published guidelines for treating rtPA-induced orolingual angioedema, although some evidence suggests that those refractory to standard antianaphylactic agents may resolve with bradykinin B2 receptor antagonists. It is important that responses to orolingual angioedema are proportionate and that patients are closely monitored.

Objectives\ud To assess the prevalence of high on-clopidogrel platelet reactivity (HCPR) in patients with ischaemic stroke or transient ischaemic attack (IS/TIA), their outcome and genetic basis of on-treatment response variability in IS/TIA patients.\ud \ud Methods\ud We conducted a comprehensive search of PubMed and EMBASE from their inceptions to March 9, 2019. Studies that reported absolute numbers/percentages of HCRP at any time point after IS/TIA onset evaluated with any type of platelet function tests, clinical outcomes and genotyping data were included.\ud \ud Results\ud Among 21 studies of 4312 IS/TIA patients treated with clopidogrel, the pooled prevalence of HCPR was 28% (95%CI: 24–32%; high heterogeneity: I2 = 88.2%, p < 0.001). Heterogeneity degree diminished across groups defined by the HCPR testing method. Clopidogrel non-responder IS/TIA patients had poorer outcome compared to responders (RR = 2.09, 95%CI: 1.61–2.70; p = 0.036; low heterogeneity across studies: I2 = 27.4%, p = 0.210). IS/TIA carriers of CYP2C19*2 or CYP2C19*3 loss of function alleles had a higher risk of HCPR compared to wild type (RR = 1.69, 95%CI: 1.47–1.95; p < 0.001; I2 = 0.01%, p = 0.475).\ud \ud Conclusions\ud This systematic review shows a high prevalence of clopidogrel resistance in IS/TIA and poor outcome in these patients. CYP2C19 polymorphisms may potentially influence clopidogrel resistance.

Background Protein convertase subtilisin–kexin type 9 (PCSK9) inhibitors effectively clear low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). We evaluated stroke admissions potentially eligible for more intensive cholesterol treatment. Methods Retrospective analysis of consecutive admissions to a hyperacute stroke unit over 5 months in 2017. Records were individually searched. Data were collected on diagnosis, risk factors, and stroke work-up. European Society of Cardiology and European Atherosclerosis Society guidelines for the management of dyslipidaemias were used for screening patients eligible for PCSK9 inhibitors. Results Of 650 patient admissions: 351 (54%) had acute ischemic stroke or transient ischemic attack (TIA), 80 (12%) hemorrhage, and 219 (34%) mimic syndromes. Patients with hemorrhage (n = 80), mimic syndromes (n = 219), and absent LDL-C, or non-HDL-C testing (n = 27) were subsequently excluded. 324 patients with acute ischemic stroke and TIA were further screened for PCSK9-inhibitor treatment eligibility. Forty-one (13%) patients with LDL-C greater than or equal to 1.8mmol/L (≥70 mg/dL) on maximal tolerated statin dose and with concomitant “very high vascular risk” were identified. “Very high vascular risk” was defined as a documented history of cardiovascular disease and/or peripheral arterial disease. Of 41 patients eligible for PCSK9 inhibitors, median age was 82 years (range 53-96); median vascular risk factors were 2 (range 1-5); 7 (17%) had TIA; 13 (31%) had history of preceding cerebrovascular events, 13 (31%) diabetes mellitus, 17 (42%) cardioembolic events, 9 (22%) lacunar syndrome, 11 (22%) symptomatic internal carotid artery stenosis (n = 9 were >70%), and 4 (10%) undetermined aetiology. Eighty-three percent patients eligible for PCSK9 inhibitors also had non-HDL-C values greater than or equal to 2.6 mmol/L. Conclusions Up to 13% of unselected acute ischemic stroke or TIA patients admitted to a hyper-acute stroke unit were potentially suitable for more intensive cholesterol treatment. Our data may act as a useful guide for sample size selection in future stroke trials testing PCSK9 inhibitors.

Nitrones (e.g. α-phenyl-N-tert-butyl nitrone; PBN) are cerebroprotective in experimental stroke. Free radical trapping is their proposed mechanism. As PBN has low radical trapping potency, we tested Sgk1 induction as another possible mechanism. PBN was injected (100 mg/kg, i.p.) into adult male rats and mice. Sgk1 was quantified in cerebral tissue by microarray, quantitative RT-PCR and western analyses. Sgk1+/+ and Sgk1−/− mice were randomized to receive PBN or saline immediately following transient (60 min) occlusion of the middle cerebral artery. Neurological deficit was measured at 24 h and 48 h and infarct volume at 48 h post-occlusion. Following systemic PBN administration, rapid induction of Sgk1 was detected by microarray (at 4 h) and confirmed by RT-PCR and phosphorylation of the Sgk1-specific substrate NDRG1 (at 6 h). PBN-treated Sgk1+/+ mice had lower neurological deficit ( p +/+ mice. PBN-treated Sgk1−/− mice did not differ from saline-treated Sgk1−/− mice. Saline-treated Sgk1−/− and Sgk1+/+ mice did not differ. Brain Sgk3:Sgk1 mRNA ratio was 1.0:10.6 in Sgk1+/+ mice. Sgk3 was not augmented in Sgk1−/− mice. We conclude that acute systemic treatment with PBN induces Sgk1 in brain tissue. Sgk1 may play a part in PBN-dependent actions in acute brain ischemia.

Current national guidelines advocate intravenous thrombolysis to treat patients with acute ischaemic stroke presenting within 4.5 hours from symptom onset, and thrombectomy for patients with anterior circulation ischaemic stroke from large vessel occlusion presenting within 6 hours from onset. However, a substantial group of patients presents with acute ischaemic stroke beyond these time windows or has an unknown time of onset. Recent studies are set to revolutionise treatment for these patients. Using MRI diffusion/FLAIR (fluid-attenuated inversion recovery) mismatch, it is possible to identify patients within 4.5 hours from onset and safely deliver thrombolysis. Using CT perfusion imaging, it is possible to identify subjects with a middle cerebral artery syndrome who have an extensive area of ischaemic brain but as yet have only a small area of infarction who may benefit from urgent thrombectomy in up to 24 hours. Here, we highlight the recent advances in late window stroke treatment and their potential contribution to clinical practice.

Catheter-based angiography is an important but invasive procedure in vascular neurology. It is used mainly for diagnosis and for planning treatment in patients with a suspected underlying vascular abnormality. It is often performed as a semiurgent, planned investigation or linked to an interventional procedure. Cerebral angiography provides high-resolution, three-dimensional, pathoanatomical data about the cerebral vasculature and also allows real-time analysis of blood flow. Contrast injections can be repeated to identify subtleties. A physical intervention may also follow angiography. For these reasons, angiography remains the gold standard for delineating vascular lesions of the brain (and spine). Permanent neurological complications are rare, approximately 1%, but become increasingly common in patients aged over 55 years. The main complications are embolic stroke, groin haematoma and contrast-induced nephropathy. In the new era of thrombectomy, it may transpire that other specialists including neurologists may learn to perform the procedure and to manage its complications.

Acute neurology is the neurological care that a patient receives in an emergency or urgent care situation. This can be adapted successfully to training in a simulation where learners are immersed in realistic scenarios in a safe, controlled and reproducible environment. In addition to teaching important technical skills that improve knowledge of the diagnosis and management of acute neurology, the simulation laboratory provides a valuable setting to improve human factors and non-technical skills, such as teamwork and leadership. Simulations are best conducted in a multiprofessional group with scenarios that allow different team members (nurses, physician associates, core medical and specialist trainees) to participate in their actual role. These training sessions require clear learning objectives, and involve designing the scenarios, running the session and ending with a structured debriefing to consolidate learning. The ultimate aim is to improve the team’s effectiveness to deliver safe acute neurological care in the emergency department and on the wards.

A 74-year-old woman gave a 6-month history of headache and intermittent face and arm movements. On initial examination, there were subtle right arm and leg choreiform movements. Her blood tests showed a low platelet count of 129×109/L (150–400), international normalised ratio of 1.2 (

Hearing disturbances are not commonly reported in stroke or transient ischemic attack. We describe a case of a 60-year-old man with fluctuating brainstem ischemia with basilar artery thrombosis where the patient has consistently described hearing "white noise," bilaterally becoming progressively louder over 10 minutes that prevented him from hearing surrounding noise including the radio. These episodes were transient and preceded episodes of hemiparesis or reduced conscious level. We correlate this to the sequential imaging findings from the patient. We discuss how this case provides in vivo evidence for localization of auditory hallucinations in the context of the auditory pathways and their blood supply, and review 25 previous cases of auditory hallucinations and possible mechanisms.

Introduction Inter-professional simulation immerses participants in realistic scenarios in a safe and reproducible environment. Its use in neurology education is limited. Learning Objectives: (i) Technical skills and knowledge in neurological emergencies (ii) Non-technical skills including communication and leadership. Methods Three acute neurology scenarios (refractory status epilepticus, coma and neuromuscular respiratory failure) with high fidelity mannequin. 30 participants (7 nursing; 8 physician9s associates; 15 medical). Mixed-methods evaluation before and after training and statistical analysis with Mann–Whitney U test. Results Analysis of pre and post course questionnaires. 56%(14/25) had previous simulation experience. On scale of 1=poor to 7 good: scored 5.66 (SD±1.14) for enjoyment and 6.28 (SD±1.21) for relevance to clinical practice. Improvement in technical skills with increased confidence in managing emergency neurology situations (pre-course: 3.5 [SD±1.45] post-course:4.63 [SD±0.956] p=0.00736). No improvement in non-technical skills:communication skills (pre-course: 4.31 [SD±1.12] post-course: 4.75 [SD±0.737] p=0.187 NS) and leadership skills (pre-course: 3.92 [SD±1.13] post-course: 4.33 [SD±0.868] p=0.271 NS). Discussion Simulation improved technical but not non-technical skills. Participants started with a higher opinion of their non-technical skill than their knowledge. Knowledge is learnt during a scenario but improvement in non-technical skills are only realised later so maybe underestimated. In future sessions we will add an introduction about non-technical skills and use the diamond debrief approach.

Background and Purpose— Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS) patients with carotid stenosis were randomized between endovascular treatment and endarterectomy. The rates of residual severe stenosis and restenosis and their contribution to recurrent symptoms was unclear. Methods— Endovascular patients were treated by balloon angioplasty alone (88%) or stenting (22%). Patches were used in 63% of endarterectomy patients. Carotid stenosis was categorized as mild (0% to 49%), moderate (50% to 69%), severe (70% to 99%), or occluded, using standardized Doppler ultrasound criteria at the examination closest to 1 month (n=283) and 1 year (n=347) after treatment. Recurrent cerebrovascular symptoms during follow-up were analyzed. Results— More patients had ≥70% stenosis of the ipsilateral carotid artery 1 year after endovascular treatment than after endarterectomy (18.5% versus 5.2%, P =0.0001). Residual severe stenosis was present in 6.5% of patients at 1 month after endovascular treatment. Between 1 month and 1 year, restenosis to ≥70% stenosis occurred in 10.5% of the endovascular group. After endarterectomy, 1.7% had residual severe stenosis at 1 month, and 2.5% developed severe restenosis. The results were significantly better after stenting compared with angioplasty alone at 1 month ( P P =0.02), but most were transient ischemic attacks and none were disabling or fatal strokes. There were no recurrent symptoms in the 9 endarterectomy patients with ≥70% stenosis at 1 year. Conclusions— Carotid stenosis 1 year after endovascular treatment is partly explained by poor initial anatomical results and partly by restenosis. The majority of patients were treated by angioplasty without stenting. Further randomized studies are required to determine whether newer carotid stenting techniques are associated with a lower risk of restenosis. The low rate of recurrent stroke in both endovascular and endarterectomy patients suggests that treatment of restenosis should be limited to patients with recurrent symptoms, but long term follow up data are required.

Coeliac disease has been associated with a variety of neurological conditions, most frequently cerebellar ataxia and peripheral neuropathy. To date, chorea has not been associated with coeliac disease. We present the case histories of 4 individuals with coeliac disease and chorea (4 women, average age of onset of chorea 61 years). Unexpectedly, most of these patients showed a notable improvement in their motor symptoms after the introduction of a gluten-free diet.

Background and Purpose — 1 H MR spectroscopy can be used to study biochemical changes occurring in the brain in stroke. We used it to examine the relationship between metabolite concentration ( N -acetyl aspartate [NAA], lactate, cholines and creatines), size of infarct, clinical deficit, and 3-month clinical outcome in patients with middle cerebral artery (MCA) territory infarction. Methods —Thirty-one patients with acute MCA territory infarction were recruited within 72 hours of the onset of symptoms. Single-voxel short echo time stimulated echo acquistion mode spectroscopy was used to obtain metabolite data from the infarct core. Metabolite concentrations were determined with use of variable projection time domain-fitting analysis. Infarct size was determined with T2-weighted images. Patient outcome groups at 3 months were “independent,” “dependent,” or “dead.” Results —All patients (100%; 95% CI 75% to 100%) who had an infarct >70 mL did poorly. Eighteen of 20 patients (90%; 95% CI 68% to 99%) with a core NAA concentration 7 mmol/L did well. Combining these results showed that all patients who had an initial infarct volume >70 mL did poorly, irrespective of the NAA concentration. Of those patients with infarcts 7 mmol/L did well (88%; 95% CI 47% to 100%), whereas those with a lower NAA concentration did poorly (80%; 95% CI 44% to 97%). There was no association between other metabolite concentrations and outcome. Conclusions —Infarct volume and NAA concentration can together predict clinical outcome in MCA infarction in humans.

Cerebral fat embolism can complicate long bone fractures and orthopaedic surgery. We present two patients with this syndrome who developed coma following long bone fracture or hip replacement surgery. Patient 1 was a 71 year old previously independent lady who was admitted following a fall and underwent total hip replacement surgery for a left neck of femur fracture. Immediately after cementing the shaft, she developed marked hypoxia, tachycardia, hypotension and pyrexia and remained intubated and sedated after surgery. Following withdrawal of sedation, she remained unconscious. Neurological examination revealed a GCS of 3/15, roving eye movements, intact brainstem reflexes, increased tone on the left side and up–going plantars. Over the next few days her GCS remained low at 5/15, with flexor motor response to pain. EEG was diffusely slow and compatible with an encephalopathic process. MRI showed innumerable small emboli on DWI (“star–field pattern”), and multiple, hyper–intense lesions on T2 and FLAIR. Bubble echo was positive and suggestive of a patent foramen ovale. Over the next four weeks, she made a dramatic recovery and one month after surgery was obeying commands, verbally communicating, oriented in time but disoriented in place. Patient 2 was a 66 year old, previously independent lady who was admitted with a femoral shaft fracture. The day following her admission, her GCS dropped to 7/15 and she developed hypoxia, tachycardia and pyrexia. Neurological examination initially did not reveal a focal deficit. During a transient improvement in GCS to 14/15, she was noted to have a right sided face and arm weakness. MRI DWI again showed the characteristic “star–field pattern”. Clinically she deteriorated again with a drop in her GCS, development of thrombocytopaenia, pulmonary emboli and nephrogenic diabetes insipidus and remained on ITU at the time of writing this abstract. Cerebral fat embolism syndrome may be under–diagnosed in clinical practice. It should be considered in the differential of coma following orthopaedic surgery and fractures. Neurological outcome has been reported to be generally good.

A 24-year-old female Punjabi student came to the UK in 2010. A right hilar mass on routine CXR and respiratory physicians performed mediastinoscopy. Right paratracheal lymph node histology demonstrated non-caseating granulomatous lymphadenitis with central necrosis. TB culture was negative. She was well and followed up with presumed quiescent sarcoidosis or TB. In September 2011, she reported 2 months of headache, 5 weeks of right eye swelling and a persistent cough. She had a right exopthalmos with left-sided weakness especially the arm. MRI brain demonstrated six enhancing intra-axial masses within the right hemisphere, six in the cerebellum and one lesion extending into the medulla. Abnormal tissue expanded into the right orbit causing exopthalmos. HIV status was negative and she was not diabetic. She was commenced on steroids and empirical quadruple therapy for TB. The presumed differentials were sarcoidosis, TB or possible malignancy Bone marrow trephine was normal (no evidence of lymphoma or organisms). Biopsy of the orbital lesion contained numerous, well preserved, fungal hyphae within the granulomas. IgE was 2000 kU/L (0–81), aspergillus precipitins >200 (0–40). Culture was positive for aspergillus flavus. Histological re-examination of the original chest lesion also confirmed aspergillus hyphae. This is a case of disseminated aspergillus infection. The patient responded well to antifungal treatment with ambisome, andulifungin IV, voroconizole and dexamethsone with resolution clinically and radiologically.

A 23-year-old left-handed female developed progressive right arm weakness and expressive dysphasia. She had papilloedema and right-sided UMN facial palsy, arm weakness and positive Babinski reflex. MRI brain demonstrated a 7.7 cm diameter heterogeneously enhancing mass lesion with surrounding vasogenic oedema lying within the left posterior frontal lobe with associated midline shift. CSF contained unmatched oligoclonal bands, consistent with a diagnosis of tumefactive multiple sclerosis. She was treated with IV methylprednisolone with complete recovery. Three years later she presented with dizziness, visual disturbance and cognitive deficits. On examination, she had a left homonymous hemianopia and a Gerstmann-like syndrome. She rapidly deteriorated with left-sided weakness, neglect, hemisensory loss, aphasia and dysphagia. MRI demonstrated an acute, demyelinating plaque of 7.2 cm involving the right parieto-occipital white matter and posterior frontal white matter with mass effect. Repeat CSF examination showed unmatched oligoclonal bands. She was treated with intravenous methylprednisolone and plasma exchange and dramatically improved. She is continuing her inpatient rehabilitation. Tumefactive lesions in MS usually convert to typical relapsing-remitting disease on recurrence. Here we present a rare case of relapsing-remitting tumefactive disease which has only previously been reported once in the literature. We have demonstrated a good response to immunosuppressive and immunomodulatory therapy.

We enjoyed A practical approach to acute vertigo by Seemungal and Bronstein in the August issue. However, we disagree that the head impulse test “will only be positive in patients with vestibular neuritis”1 and so …