Meta-analysis and systematic review of population-based epidemiological studies in idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH) is positively associated with obesity, mostly in young women. The global increase in obesity may influence the burden of IIH. Using the PubMed, Embase, MEDLINE and Web of Science databases, a meta-analysis and systematic review of epidemiological studies of IIH were performed up to June 2017. Temporal changes in IIH incidence were measured, and incidence rates of IIH were correlated with country-specific World Health Organization obesity rates. Prevalence data and shunting rates of IIH were recorded. The quality of epidemiological studies was assessed using the Standards of Reporting of Neurological Disorders (STROND) criteria. In 15 identified studies, there were 889 patients (87% women), mean age 29.8 years. The incidence of IIH ranged from 0.03 to 2.36 per 100 000 per year. The pooled incidence of IIH was 1.20 per 100 000 per year although there was very high heterogeneity (I2 98%). The incidence rates of IIH were correlated with country-specific prevalence of obesity (Spearman's correlation 0.82, P < 0.01). The prevalence of IIH was rarely recorded. A shunting procedure was reported in 8% of patients. STROND criteria were variably reported, median of 26.5 of 43 (range 16-35). IIH is a public health concern as increased obesity prevalence is associated with increased incidence of IIH. A better quality of epidemiological studies is required to improve understanding of IIH and inform health policy for IIH management.

Impact of social prescribing on general practice workload and polypharmacy.

OBJECTIVES: Social prescribing has emerged as a useful tool for helping patients overcome some of the social and behavioural determinants of poor health. There has been little research on the impact of social prescribing on use of primary healthcare resources. This study sought to determine whether social prescribing activities influenced patient-general practitioner (GP) contacts and polypharmacy. STUDY DESIGN: Quality-improvement design with social prescribing activity interventions from an urban general practice in Northern Ireland. METHODS: Patients over 65 years of age with a chronic condition who attended their GP frequently or had multiple medications were offered a social prescribing activity. Participants' contacts with GP and the new repeat prescriptions before and during the social prescribing activity were measured. The total number of repeat prescriptions per patient was compared at the time of referral and 6-12 months later. Indications for referral, primary diagnoses and reasons for declining participation in a social prescribing activity after referral were prospectively recorded. RESULTS: Sixty-eight patients agreed to participate but only 28 (41%) engaged in a prescribed social activity. There was no statistically significant difference in GP contacts (visits to GP, home visits or telephone calls) or number of new repeat prescriptions between referral and completion of 12 weeks of social prescribing activity. Similarly there was no statistically significant difference in the total number of repeat prescriptions between referral and 6-12 months after social prescribing activity in either intention to treat or per protocol analyses. Social prescribing participants had similar demographic factors. Mental health issues (anxiety and/or depression) were more common among participants than those who were referred but declined participation in a social prescribing activity (P = 0.022). CONCLUSIONS: While social prescribing may help patients' self-esteem and well-being, it may not decrease GP workload. Further research is required to optimise social prescribing benefits.

Educational interventions in neurology: a comprehensive systematic review.

A fear of neurology and neural sciences (neurophobia) may have clinical consequences. There is therefore a need to formulate an evidence-based approach to neurology education. A comprehensive systematic review of educational interventions in neurology was performed. BEI, Cochrane Library, Dialog Datastar, EBSCO Biomedical, EBSCO Psychology & Behavioral Sciences, EMBASE, ERIC, First Search, MDConsult, Medline, Proquest Medical Library and Web of Knowledge databases were searched for all published studies assessing interventions in neurology education among undergraduate students, junior medical doctors and residents up to and including July 2012. Two independent literature searches were performed for relevant studies, which were then classified for level of evidence using the Centre of Evidence-based Medicine criteria and four levels of Kirkpatrick educational outcomes. One systematic review, 16 randomized controlled trials (RCTs), nine non-randomized cohort/follow-up studies, 33 case series or historically controlled studies and three mechanism-based reasoning studies were identified. Educational interventions showed favourable evaluation or assessment outcomes in 15 of 16 (94%) RCTs. Very few studies measured subsequent clinical behaviour (two studies) and patient outcomes (one study). There is very little high quality evidence of demonstrably effective neurology education. However, RCTs are emerging, albeit without meeting comprehensive educational criteria. An improving evidence base in the quality of neurology education will be important to reduce neurophobia.

Hyperglycaemia monitoring and management in stroke care: policy vs. practice.

AIM: To evaluate the extent to which hyperglycaemia was monitored and managed among patients admitted to hospital with acute stroke and transient ischaemic attack. METHODS: We conducted a retrospective cohort study involving a review of the records of 112 patients consecutively admitted with acute stroke or transient ischaemic attack to all three district general hospitals in one Health and Social Care Trust in Northern Ireland from 1 January to 15 April 2008. Glucose results for each of the first 5 days of hospital admission were ascertained. We compared interventions, clinical outcome and discharge planning between patients who experienced glucose ≥ 7.8 mmol/l in the first 5 days, and patients with lower glucose results. RESULTS: The daily prevalence rate of hyperglycaemia > 7.8 mmol/l across the first 5 days ranged from 24 to 34%. A total of 41 (37%) patients experienced hyperglycaemia on at least one occasion during the first 5 days. A history of diabetes mellitus prompted near patient glucose testing, but, among patients without diagnosed diabetes, glycaemia was under-monitored. Hyperglycaemia was a persisting trend, was under-treated and under-reported to general practitioners. Elevated glucose results failed to influence higher rates of fasting plasma glucose tests and BMI assessment. CONCLUSIONS: There is a need for greater vigilance in the detection of hyperglycaemia and undiagnosed diabetes mellitus among patients admitted to hospital with stroke or transient ischaemic attack.

The value of a liaison neurology service in a district general hospital.

BACKGROUND: Healthcare development in the UK has resulted in an increase in neurologists working in district general hospitals. METHODS: The aim of the study was to determine the use of a neurologist for inpatient diagnosis and management, and to measure a neurologist's diagnostic reliability in a district general hospital over a 27-month period. Patient data were prospectively recorded. Follow-up was performed independently by two clinicians reviewing the medical notes. Reasons for diagnostic change were determined. RESULTS: 306 inpatients were referred to the neurologist between 1 January 2007 and 31 March 2009 (2% of medical admissions). Mean (SD) age was 49.3 (18.8) years, and the female/male ratio was 1.2:1. Epilepsy and stroke were the most common diagnoses. Diagnostic concordance between referring physician and neurologist ranged from κ score 0.13 (spinal pathology) to 0.83 (central nervous system infection). Neurological opinion resulted in diagnostic change in 38.2% and management change in 88.8%. Only 1.6% of patients remained without a diagnosis, a fourfold improvement from physician referral. After medical records had been reviewed, 3.3% of inpatient diagnoses (10 of 306 patients) changed from the original diagnosis by the neurologist. Specialist investigation helped in revising diagnoses in four of the 10 diagnostic changes. CONCLUSION: This study shows that in a district general hospital a neurologist can contribute to inpatient diagnosis and management with minimal diagnostic change over time, suggesting reliability of this service.

The reliable measurement of temporal trends in mortality attributed to epilepsy and status epilepticus in Northern Ireland between 2001-2015.

PURPOSE: Epilepsy mortality is of considerable public health concern, as a leading cause of premature neurological death. Recent English and Welsh mortality data suggests a falling mortality rate where epilepsy was the underlying cause of death, predominantly due to a reduction in status epilepticus (SE) mortality. We sought to validate this finding in Northern Ireland. METHODS: Officially recorded death certificate data related to epilepsy and SE were obtained from the Northern Ireland statistics and research agency. Data were analysed from 2001 to 2015. The outcomes were the age-adjusted mortality rate for epilepsy and SE. External validation of SE deaths was carried out using data from an intensive care national audit and research centre database. RESULTS: From 2001 until end of 2015, epilepsy was recorded at death certification in 1484 cases. 458 deaths were considered due to epilepsy. Among 75 in whom SE was recorded, SE was the cause of death in 46 patients. External validation found 103 total deaths related to SE in ICU departments in Northern Ireland, suggesting an overall under-ascertainment of officially recorded statistics. With respect to the 2013 European Standard Population, the mean age-adjusted mortality rate for epilepsy was 1.9 (95% C.I. 1.73-2.07) per 100,000 person years. For SE the mean age-adjusted mortality rate was 2.1 (95% C.I. 0.15-0.27) per 100,000 person years. CONCLUSIONS: Death certification in SE is likely to be an underestimate of the reality. Further efforts are urgently needed to determine the extent of SE-related deaths and all deaths in patients with epilepsy.

Potential for quality improvement of acute stroke management in a district general hospital.

BACKGROUND: Stroke units and thrombolysis are evidence based treatments for stroke patients. Few studies have prospectively assessed the success of, and obstacles to implementation of such strategies in patients admitted to district general hospitals. OBJECTIVE: To document delays in admissions of acute stroke patients to hospital, failures in accessing a stroke unit and the clinical impact of missed opportunities for intervention in acute stroke patients. DESIGN, SETTING AND METHODS: Prospective observational study in a district general hospital in Northern Ireland. Delays, demographic details, risk factors, stroke severity and classification were recorded prospectively in all stroke patients admitted to a district general hospital from 22 March 2004 until 21 March 2005. Using established numbers needed to treat to prevent disability or death, the clinical impact of the lost opportunities was determined. RESULTS: Of 171 acute stroke patients 115 (67%) spent some or all of their hospital stay in a stroke unit. Less severe strokes, living alone and attending a general practitioner all independently delayed hospital admission. Nineteen (12.5%) ischaemic stroke patients would have been eligible for intravenous thrombolysis treatment. Admitting all patients to the stroke unit would have gained independence for two patients, allowed two more patients to live at home, and prevented one death. Failure to thrombolyse eligible acute ischaemic stroke patients resulted in six patients having more disability, two of whom may have lost their independence. CONCLUSIONS: Improved stroke unit access is required in this district general hospital. Reorganisation of acute stroke services should allow thrombolysis for acute ischaemic stroke in most district general hospitals.

Driving after a transient ischaemic attack or minor stroke.

The frequency of adherence to the UK Driver and Vehicle Licensing Authority (DVLA) guidelines for patients referred to a neurovascular clinic is not known. Of 166 consecutive patients, 95 (57.2%) had a group 1 licence and 71 (42.7%) drove within a month of the event. Fifty of 85 (59%) transient ischaemic attack (TIA)/minor stroke patients had a licence and 30 (35%) drove within a month of the TIA/stroke. Compliance with DVLA driving guidelines is poor among patients referred to hospital with suspected TIA or minor strokes.

Quality assurance of neuroradiology in a District General Hospital.

BACKGROUND: An increasing number of neurologists in District General Hospitals (DGHs) rely on local neuroimaging reports from general radiologists. AIM: To determine the level of disagreement between general radiologists and neuroradiologists in reporting neuroimaging from patients referred to a neurologist. DESIGN: Prospective observational study. METHODS: We studied 232 patients referred for a neuroradiologist's report on neuroimaging over a 17-month period. Pre-planned comparisons included primary and secondary report findings, length of report and suggestions for additional investigations. RESULTS: Of the 593 patients assessed during the study period, a neuroradiologist's report was sought for 232 (39%): 119 men, 113 women, mean age 46.1 (SD 17.6) years. Primary findings differed in 37 patients (15.9%) (95%CI 11.5-21.3). Reports from neuroradiologists changed subsequent management in 31 (13.4%) (95%CI 9.3-18.4). Differences in secondary findings occurred in 52 (22.4%) (95%CI 17.2-28.3), and differences in either primary or secondary outcomes in 77 (33.2%) (95%CI 27.2-39.6). The level of disagreement in primary findings was as frequent among patients investigated with magnetic resonance imaging as among computerized tomogram-only patients (p = 0.13). Neuroradiologists recommended additional investigations for 24 patients (10.3%) (95%CI 6.7-15.0) and provided longer reports than general radiologists (p < 0.001). DISCUSSION: Neuroimaging reports of some patients differ substantially between general radiologists and neuroradiologists. Optimal management of neurological patients in DGHs may require timely access to neuroradiologists.

Secular stroke trends: early life factors and future prospects.

Stroke mortality rates have declined during the second half of the 20th century in developed countries. Possible reasons for this include preventive measures, recent environmental changes impacting on adult health risks, and more distant environmental influences on childhood health. Data from a number of populations in Europe and the USA suggest that a decrease in early life blood pressure, occurring since the beginning of the 20th century, may have been an important determinant of declining stroke incidence rates and cardiovascular disease mortality in general. Advances in stroke epidemiology are increasing the accuracy of case ascertainment, and neuroimaging refinements (particularly MRI) are improving the accuracy of stroke type and subtype diagnoses. Although some risk factors are common to ischaemic and haemorrhagic stroke, there is accumulating evidence of differing aetiology. There is also an increasing recognition that early life factors may influence stroke risk. Despite the encouraging decline in stroke incidence, there is evidence of a recent increase in mean blood pressure in young people observed in the USA and UK, prompting concern that favourable trends in stroke risk may not be maintained. Reducing early life blood pressure in a population and delaying the onset of hypertension, along with effective measures to combat obesity, are required to avoid a reversal in stroke incidence trends in developed countries, and to prevent the anticipated increase in the burden of stroke in developing countries.

The apolipoprotein E epsilon2 allele and the pathological features in cerebral amyloid angiopathy-related hemorrhage.

Cerebral amyloid angiopathy (CAA) is associated with apolipoprotein E (APOE gene, apoE protein) polymorphism: current evidence suggests that the epsilon4 allele is a risk factor for the development of CAA and the epsilon2 allele predisposes to hemorrhage. We sought to determine the relationship between the APOE epsilon2 allele and both the immunoreactivity profiles and vascular complications of CAA. We performed immunohistochemistry for amyloid beta-protein (A beta), apoE, cystatin C, and activated microglia, and examined the morphology of cortical and leptomeningeal vessels in 37 CAA-related hemorrhage (CAAH), 26 Alzheimer disease (AD) patients, and 20 controls. The extent of immunostaining of vessels for A beta, apoE, cystatin C, and perivascular activated microglia increased from controls through AD to a maximum in CAAH patients. Among cases with CAA (37 CAAH, 19 AD, and 6 controls, n = 62) vascular apoE (p < 5 x 10(-4)), cystatin C (p < 10(-4)), activated microglia (p < 10(-4)), vessels with a high ratio of wall thickness to lumen diameter (p < 0.003) as well as dilated/microaneurysmal vessels (p < 0.01) were present more frequently in patients with hemorrhage than without; however, these features were not associated with the APOE epsilon2 allele. Fibrinoid necrosis alone was associated with the APOE epsilon2 allele (p < 0.04) and we suggest that over-representation of APOE epsilon2 in CAAH may result from its association with fibrinoid necrosis.

Association between interleukin-1A polymorphism and cerebral amyloid angiopathy-related hemorrhage.

BACKGROUND AND PURPOSE: It has been suggested that the interleukin-1A (IL-1A) allele 2 is a risk factor for Alzheimer's disease (AD). Because cerebral amyloid angiopathy-related hemorrhage (CAAH) often coexists with AD, we examined the IL-1A polymorphism in CAAH. METHODS: In a case-control study, patients with pathologically verified CAAH, AD patients without intracerebral hemorrhage, and neuropathologically normal control subjects were studied. DNA was extracted from brain tissue, and IL-1A was genotyped. Logistic regression was used to examine the IL-1A polymorphism in CAAH patients with and without AD compared with AD and non-AD control subjects. RESULTS: There were 42 patients with CAAH, 232 AD patients, and 167 non-AD control subjects. In age-adjusted analyses, there was no association between possession of IL-1A allele 2 and risk of CAAH compared with AD control subjects (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.45 to 1.97; P=0.87) or non-AD control subjects (OR, 0.94; 95% CI, 0.47 to 1.87; P=0.86). Stratifying for the presence of apolipoprotein E epsilon2 or epsilon4 demonstrated the known increased risk of CAAH from these lipoprotein E alleles. Subgroup analyses demonstrated a nonsignificant excess of the IL-1A 2,2 genotype in patients with CAAH and AD compared with those CAAH patients who did not have histological evidence indicating AD (OR, 2.17; 95% CI, 0.15 to 122.3; P=0.64). Comparisons between CAAH patients with AD and AD control subjects and between CAAH patients without AD and non-AD control subjects did not demonstrate an association between CAAH and possession of either the IL-1A allele 2 or the 2,2 genotype. CONCLUSIONS: The IL-1A allele 2 or 2,2 genotype does not appear to be a major risk factor for CAAH.

The role of apolipoprotein E in Alzheimer's disease, acute brain injury and cerebrovascular disease: evidence of common mechanisms and utility of animal models.

The epsilon 4 allele of apolipoprotein E (APOE denotes gene; apoE denotes protein) is a major risk factor for Alzheimer's disease (AD). More recent evidence indicates an association with a poor outcome after acute brain injury including that due to head trauma and intracerebral hemorrhage. APOE gene polymorphism also influences the risk of hemorrhage in cerebral amyloid angiopathy. These diverse brain disorders seem to have some mechanisms in common. The multiplicity of the roles of apoE within the central nervous system is currently being unraveled. For example, apoE can interact with amyloid beta-protein and tau, proteins central to the pathogenesis of AD. In addition to these effects, it is proposed that one of the major functions of apoE is to mediate neuronal protection, repair and remodeling. In all of the different roles proposed, there are marked apoE-isoform specific differences. Although it remains to be clarified which is the most important mechanism(s) in each disorder in which apoE is involved, these isoform specific differences seem to underly a genetically determined susceptibility to outcome from acute brain injury and to AD with APOE epsilon 4 conferring relative vulnerability. This review focuses on apoE research, from clinical studies to animal models, in AD, acute brain injury and cerebrovascular disease and explores the common mechanisms that may explain some of the complex underlying neurobiology.

Traumatic Brown-Séquard-plus syndrome.

BACKGROUND: In the 1840s Brown-Séquard described the motor and sensory effects of sectioning half of the spinal cord. Penetrating injuries can cause Brown-Séquard or, more frequently, Brown-Séquard-plus syndromes. OBJECTIVE: To report the case of a 25-year-old man who developed left-sided Brown-Séquard syndrome at the C8 level and left-sided Horner syndrome plus urinary retention and bilateral extensor responses following a stab wound in the right side of the neck. RESULTS: Magnetic resonance imaging demonstrated a low cervical lesion and somatosensory evoked potentials confirmed the clinical finding of left-side dorsal column disturbance. At follow-up, the patient's mobility and bladder function had returned to normal. CONCLUSION: This patient recovered well after a penetrating neck injury that disturbed function in more than half the lower cervical spinal cord (Brown-Séquard-plus syndrome).

Prospective study of apolipoprotein E genotype and functional outcome following ischemic stroke.

BACKGROUND: The apolipoprotein E (APOE) epsilon 4 allele is a marker of adverse outcome following head injury and intracerebral hemorrhage. Transgenic animal data in a focal cerebral ischemia model suggest that the epsilon 4 allele increases infarct size and functional impairment. OBJECTIVE: To determine if APOE genotype is associated with functional recovery from ischemic stroke. DESIGN: Prospective study. SETTING: Stroke service at a university teaching hospital. PATIENTS: Patients with clinical and neuroimaging findings (computed tomography or magnetic resonance imaging) compatible with an acute ischemic stroke. MAIN OUTCOME: Functional outcome by Barthel index (BI) and modified Rankin scale (mRS) was compared for epsilon 3/epsilon 3 patients vs epsilon 4 carriers and vs epsilon 2 carriers at 1 and 3 months. Univariate predictors of 3-month outcome were examined in a multivariate analysis. RESULTS: One hundred eighty nine patients were enrolled: 100 women, 89 men (mean +/- SD age, 69.4 +/- 11.0 years). There were 25 epsilon 2 alleles (frequency, 0.07), 292 epsilon 3 alleles (0.77), and 61 epsilon 4 alleles (0.16). Baseline National Institutes of Health Stroke Scale scores and Oxfordshire Community Stroke Project classifications were similar in all groups (epsilon 3/epsilon 3, epsilon 4, and epsilon 2 carriers). One-month (BI, P = .64; mRS, P = .59) and 3-month (BI, P = .87; mRS, P = .73) outcomes were not associated with possession of either epsilon 4 or the epsilon 2 allele. Baseline National Institutes of Health Stroke Scale scores (P < .001) and age (P = .002) were significant predictors of 3-month BI and mRS outcomes in multivariate analyses. CONCLUSIONS: Although there is a robust influence of APOE polymorphism on functional recovery after some types of brain injury in humans, it does not exert a major influence on injury severity or functional recovery following ischemic stroke. Arch Neurol. 2000;57:1480-1484

APOE genotype as a risk factor for ischemic cerebrovascular disease: a meta-analysis.

OBJECTIVE: To determine whether a specific apolipoprotein E (APOE) polymorphism is a risk factor for ischemic cerebrovascular disease (CVD; stroke or TIA). BACKGROUND: The APOE epsilon4 allele is overrepresented in AD, atherosclerosis, and ischemic heart disease. In addition, epsilon4 carriers have higher plasma cholesterol levels than non-epsilon4 carriers. METHODS: Using Medline (OVID and PubMed), a search was performed for all studies that examined APOE in ischemic CVD. The authors identified nine case-control studies that were suitable for analysis. RESULTS: There were 926 patients with ischemic stroke or TIAs and 890 age- and sex-matched control subjects. Overall analysis revealed a significantly higher APOE-epsilon4 allelic frequency in affected patients compared with control subjects (0.14 versus 0.09; odds ratio, 1.68; 95% CI, 1.36 to 2.09; p<0.001). There was a significant excess of the epsilon3 allele (0.85 versus 0.80) but not the epsilon2 allele (0.06 versus 0.06) in the control subjects compared with the ischemic CVD patients. Seven studies had data on APOE genotypes. Carriers of epsilon4 were more frequent among ischemic CVD patients than control subjects (27% versus 18%; odds ratio, 1.73; 95% CI, 1.34 to 2.23; p<0.001). CONCLUSIONS: The APOE-epsilon4 allele and carriers of epsilon4 are more frequent among patients with ischemic CVD compared with control subjects. The epsilon2 allele does not appear to be protective for ischemic CVD. These findings imply a role for the APOE genotype in the pathogenesis of some cases of ischemic CVD.

Selective defect of baroreflex blood pressure buffering with intact cardioinhibition in a woman with familial aniridia.

We report a symptomatic failure of the baroreceptor blood pressure (BP) buffering mechanism in a woman with familial aniridia. Her baseline BP oscillated at 0.1 Hz, the frequency of Mayer waves, with increased amplitude on standing without orthostatic hypotension. Although sudomotor function was normal, cutaneous thermoregulatory function and BP response to Valsalva's maneuver were abnormal. The defective BP buffer mechanism suggests Mayer waves could be a sympathetic mediated cardiovascular resonance. Baroreceptor cardioinhibition was intact. We presume that the lesion is in the rostral aspect of the dorsal medulla oblongata.

Absence of cystatin C mutation in sporadic cerebral amyloid angiopathy-related hemorrhage.

In Icelandic pedigrees a cystatin C mutation, glutamine 68 (L68Q), causes autosomal dominant cerebral amyloid angiopathy-related hemorrhage (CAAH). We examined 33 patients with sporadic CAAH for this mutation. None carried L68Q and, including this report, only one of 52 published cases of sporadic CAAH has had the cystatin C mutation. Despite vascular colocalization of cystatin C with amyloid beta-protein, cystatin C L68Q is rare in sporadic CAAH.

Apolipoprotein E genotype, coagulation, and survival following acute stroke.

The authors hypothesized that divergent influences of the APOE epsilon4 allele on ischemic and hemorrhagic stroke survival might result from differences in coagulation profiles. In 49 hemorrhagic stroke patients, epsilon4 carriers had higher partial thromboplastin time ratios (p < 0.01) than non-epsilon4 carriers. Among 529 ischemic stroke patients, increasing epsilon4 allele dose was associated with improved survival (p = 0.03) after adjusting for baseline NIH stroke scale (p = 0.00001) and partial thromboplastin time ratio (p = 0.01). Relative anticoagulation does not fully explain the survival advantage in epsilon4-carrying ischemic stroke patients.