Pattern of spread and prognosis in lower limb-onset ALS.

Our objective was to establish the pattern of spread in lower limb-onset ALS (contra- versus ipsi-lateral) and its contribution to prognosis within a multivariate model. Pattern of spread was established in 109 sporadic ALS patients with lower limb-onset, prospectively recorded in Oxford and Sheffield tertiary clinics from 2001 to 2008. Survival analysis was by univariate Kaplan-Meier log-rank and multivariate Cox proportional hazards.

Low risk of ipsilateral stroke in patients with asymptomatic carotid stenosis on best medical treatment: a prospective, population-based study.

Background And Purpose: The annual risk of ischemic stroke distal to > or =50% asymptomatic carotid stenoses was approximately 2% to 3% in early cohort studies and subsequent randomized trials of endarterectomy. This risk might have fallen in recent years owing to improvements in medical treatment, but there are no published prognostic data from studies initiated within the last 10 years.

Methods: In a population-based study of all patients with transient ischemic attack (TIA) or stroke in the Oxford Vascular Study, we studied the risk of TIA and stroke in patients with > or =50% contralateral asymptomatic carotid stenoses recruited consecutively from 2002 to 2009 and given intensive contemporary medical treatment.

Lower rates of intervention for symptomatic carotid stenosis in women than in men reflect differences in disease incidence: a population-based study.

Background And Purpose: Although there is little sex difference in the age-specific incidence of transient ischemic attack (TIA) and stroke, substantially more men than women undergo endarterectomy/stenting for symptomatic carotid stenosis. Sexism in referral for investigation or intervention has been proposed as an explanation; however, a lower incidence of carotid disease in women or reluctance to undergo intervention might also be responsible.

Methods: We determined the sex-specific incidence of symptomatic carotid stenosis and subsequent endarterectomy/stenting from 2002 to 2009 in consecutive patients with TIA or nondisabling ischemic stroke in the Oxford Vascular Study.

Head and other physical trauma requiring hospitalisation is not a significant risk factor in the development of ALS.

The pathogenesis of ALS is not fully understood but, as an overwhelmingly sporadic disorder, it is likely to result from a complex mixture of polygenic and environmental risk factors operating in the context of an ageing nervous system. Physical trauma, in particular head injury, has been variably associated with both Alzheimer's and Parkinson's disease, and largely discounted in relation to multiple sclerosis. Several case-control studies in ALS have reported an association with physical trauma or head injury, but such studies are greatly limited by recall bias.

Normal cortical energy metabolism in migrainous stroke: A 31P-MR spectroscopy study.

Background And Purpose: Previous (31)P-magnetic resonance spectroscopy ((31)P-MRS) studies have shown that cerebral cortical energy metabolism is abnormal in migraine and that cortical energy reserves decrease with increasing severity and duration of aura. Migrainous infarction is a rare complication of migraine with aura, and its pathophysiology is poorly understood. We used (31)P-MRS to determine whether migrainous stroke shows similar interictal abnormalities in cortical energy metabolism as severe, prolonged aura.

Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis.

Background: Reliable data on the prevalence and predictors of post-stroke dementia are needed to inform patients and carers, plan services and clinical trials, ascertain the overall burden of stroke, and understand its causes. However, published data on the prevalence and risk factors for pre-stroke and post-stroke dementia are conflicting. We undertook this systematic review to assess the heterogeneity in the reported rates and to identify risk factors for pre-stroke and post-stroke dementia.

Population-based study of risk and predictors of stroke in the first few hours after a TIA.

Background: Several recent guidelines recommend assessment of patients with TIA within 24 hours, but it is uncertain how many recurrent strokes occur within 24 hours. It is also unclear whether the ABCD2 risk score reliably identifies recurrences in the first few hours.

Methods: In a prospective, population-based incidence study of TIA and stroke with complete follow-up (Oxford Vascular Study), we determined the 6-, 12-, and 24-hour risks of recurrent stroke, defined as new neurologic symptoms of sudden onset after initial recovery.

Risk of recurrent stroke, other vascular events and dementia after transient ischaemic attack and stroke.

The early risk of recurrence after transient ischaemic attack (TIA) or minor stroke is high, ranging from 11% at 7 days in population-based studies, where patients are seen non-urgently, to 3% at 7 days in studies where patients are seen urgently in specialist services. In long-term (up to 10 years) studies of vascular risks after TIA and stroke, the risk of stroke is highest early after the event, and then falls, whereas the risk of coronary events is constant over the follow-up period at around 2% per year. In contrast to the early risk after TIA and stroke, the long-term risks are more dependent on the underlying vascular risk factors than the characteristics of the event itself.

Epistasis among HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci determines multiple sclerosis susceptibility.

Multiple sclerosis (MS), a common central nervous system inflammatory disease, has a major heritable component. Susceptibility is associated with the MHC class II region, especially HLA-DRB5*0101-HLA-DRB1*1501-HLA-DQA1*0102-HLA-DQB1*0602 haplotypes(hereafter DR2), which dominate genetic contribution to MS risk. Marked linkage disequilibrium (LD) among these loci makes identification of a specific locus difficult.

Reliable estimation of the proportion of minor stroke due to intracerebral haemorrhage.

Background: A previous hospital clinic-based study estimated that 3.5% of minor strokes are due to primary intracerebral haemorrhage, but the confidence intervals were wide. Moreover this figure may be an underestimate in older patients, who are less likely to be referred to secondary care, and who may have higher rates of intracerebral haemorrhage.

Is intravenous recombinant plasminogen activator effective up to 4.5 h after onset of ischemic stroke?

Randomized, controlled trials and subsequent observational studies in routine clinical practice have shown that intravenous recombinant tissue plasminogen activator is safe and effective when used in selected patients within 3h of the onset of acute ischemic stroke. Results of the ECASS III (European Cooperative Acute Stroke Study III) trial have now confirmed the finding of a previous meta-analysis of data from individual patients from smaller trials, which showed that the time-window for benefit actually extends to 4.5h.

Endarterectomy for symptomatic and asymptomatic carotid stenosis.

Recent research helped to identify which patients are likely to benefit most from carotid endarterectomy and when the intervention is most effective in patients with symptomatic stenosis. Individual risk modeling is useful in selecting patients for endarterectomy for symptomatic stenosis, although timely surgery and optimal medical treatment are of equal importance. Long-term benefit from endarterectomy for asymptomatic carotid stenosis is limited, and further research is required to identify individuals with asymptomatic stenosis who have the most to gain from surgery.

Prognosis and management in the first few days after a transient ischemic attack or minor ischaemic stroke.

The risk of recurrent stroke during the first few days after a transient ischaemic attack (TIA) or minor stroke is very much higher than previously estimated. However, there is considerable international variation in how patients with suspected TIA or minor stroke are managed in the acute phase, some healthcare systems providing immediate emergency inpatient care and others providing non-emergency outpatient clinic assessment. This review considers what is known about the early prognosis after TIA and minor ischaemic stroke, what factors identify individuals at particularly high early risk of stroke, and what evidence there is that urgent preventive treatment is likely to be effective in reducing the early risk of stroke.

Medical and surgical management of symptomatic carotid stenosis.

Carotid bifurcation stenosis is an important cause of ischaemic stroke, particularly in patients with recent transient ischaemic attack or minor stroke. Large randomized trials of endarterectomy have shown that surgery reduces the risk of stroke in patients with > or = 50% recently symptomatic carotid stenosis, and more recent research has gone some way to wards identifying which patients benefit the most. Individual risk modelling has been shown to be useful in selecting patients with the most to gain from endarterectomy for symptomatic stenosis, although timely surgery and optimal medical treatment are of equal importance.

Genetics of ischaemic stroke; single gene disorders.

Examples of single gene disorders have been described for all major subtypes of ischaemic stroke: accelerated atherosclerosis and subsequent thrombo-embolism (e.g. homocysteinuria), weakening of connective tissue resulting in arterial dissections (e.

Prognostic models.

An appreciation of prognosis is essential for effective clinical practice, in neurology as in other fields. Predicting risk of a poor outcome in individuals, or at least in well-defined groups of individuals, is necessary to properly inform patients about what the future holds for them, and the likely benefits of treatment. Despite the various pitfalls in the derivation and validation of prognostic models (or scores), there are an increasing number of useful models available to help patients and clinicians in routine neurology practice.

Reliability of clinical diagnosis of the symptomatic vascular territory in patients with recent transient ischemic attack or minor stroke.

Background And Purpose: Knowledge of the vascular territory of a recent transient ischemic attack or minor stroke determines appropriate investigations and the need for territory-specific interventions such as endarterectomy and stenting. However, there are few published data on the accuracy of clinical assessment of the vascular territory.

Methods: We studied agreement of clinical diagnosis of vascular territory in consecutive patients with transient ischemic attack or minor stroke with diffusion-weighted MRI who had an acute ischemic lesion(s) in a single vascular territory (determined by a neuroradiologist).

Comparison of the blood pressure response to food in two clinical subgroups of multiple system atrophy (Shy-Drager syndrome).

Multiple system atrophy (MSA) is a progressive disorder in which autonomic features vary at different stages. Abnormal cardiovascular responses are common and it is now recognized that factors in daily life, such as exercise or food ingestion, can lower blood pressure (BP) substantially. The BP response to exercise differs in the cerebellar (MSA-C) and parkinsonian (MSA-P) forms of MSA.

Environmental factors and multiple sclerosis.

Studies in Canada have provided strong evidence that environmental factors act at a population level to influence the unusual geographical distribution of multiple sclerosis (MS). However, the available data accommodate more than one type of environmental effect. Migration studies show that changes to early environment can greatly affect risk, and there are recent indications that risk can be altered in situ.

Prediction and prevention of stroke in patients with symptomatic carotid stenosis: the high-risk period and the high-risk patient.

Carotid bifurcation stenosis is an important cause of ischaemic stroke, particularly in patients with recent transient ischaemic attack or minor stroke. Large randomised trials of endarterectomy have shown that surgery reduces the risk of stroke in patients with > or =50% recently symptomatic carotid stenosis, but more recent research has shown that the effectiveness of surgery is highly dependent on timing and on patient selection. Early surgery has been shown to be essential to reduce the high risk of stroke in the first few weeks after a TIA or minor stroke, and targeting treatment on the basis of timing and individual risk modelling has been shown to be useful in selecting patients with most to gain from endarterectomy for symptomatic stenosis.

Current status of carotid endarterectomy and stenting for symptomatic carotid stenosis.

There is still considerable uncertainty about the place of carotid stenting in patients with recently symptomatic carotid bifurcation stenosis. Most reviews of carotid endarterectomy versus carotid stenting concentrate on technical aspects and advances in stenting, but the techniques involved in both carotid endarterectomy and stenting are evolving. In addition to reviewing the results of the various randomised controlled trials of carotid endarterectomy versus stenting for symptomatic carotid stenosis, this review considers recent advances and current best practice for endarterectomy.

Sex differences in heritability of ischemic stroke: a systematic review and meta-analysis.

Background And Purpose: Using data from Oxfordshire, UK, we recently showed that women are more likely than men to have a family history of stroke in female versus male first degree relatives. To test the generalizability of this finding, we did a comprehensive systematic review of all available published and unpublished data.

Methods: Studies were included in the present review if they reported the frequency of family history of stroke in relation to sex of parent or proband.

Risk of stroke early after transient ischaemic attack: a systematic review and meta-analysis.

Background: Stroke is often preceded by transient ischaemic attack (TIA), but studies of stroke risk after TIA are logistically difficult and have yielded conflicting results. However, reliable estimation of this risk is necessary for planning effective service provision, clinical trials, and public education. We therefore did a systematic review of all studies of stroke risk early after TIA.