Robert D. Henderson

Angiographically Defined Collateral Circulation and Risk of Stroke in Patients With Severe Carotid Artery Stenosis

BACKGROUND AND PURPOSE Blood supply through collateral pathways improves regional cerebral blood flow and may protect against ischemic events. The effect of collaterals on the risk of stroke and transient ischemic attack (TIA), in the presence of angiographic severe internal carotid artery (ICA) stenosis, was assessed. METHODS Angiographic collateral filling through anterior communicating and posterior communicating arteries and retrograde filling through ophthalmic arteries were determined in all patients at entry into the North American Symptomatic Carotid Endarterectomy Trial. Kaplan-Meier event-free survival analyses were performed on 339 medically treated and 342 surgically treated patients. RESULTS The presence of collaterals supplying the symptomatic ICA increased with severity of stenosis. Two-year risk of hemispheric stroke in medically treated patients with severe ICA stenosis was reduced in the presence of collaterals: 27.8% to 11.3% (P=0.005). Similar reductions were observed for hemispheric TIA (36.1% versus 19.1%; P=0.008) and disabling or fatal strokes (13.3% versus 6.3%; P=0.11). For surgically treated patients, the perioperative risk of hemispheric stroke was 1.1% in the presence of collaterals versus 4. 9% when absent. The 2-year stroke risks for surgical patients with and without collaterals were 5.9% versus 8.4%, respectively. Neither comparison in the surgical group was statistically significant. The observed reductions were independent of the degree of ICA stenosis and other vascular risk factors. CONCLUSIONS Collaterals are associated with a lower risk of hemispheric stroke and TIA, both long term and perioperatively. Angiographic identification of collaterals assists in identifying patients with severe ICA stenosis at lower risk of stroke and TIA.

Apparent Fibre Density: a novel measure for the analysis of diffusion-weighted magnetic resonance images.

This article proposes a new measure called Apparent Fibre Density (AFD) for the analysis of high angular resolution diffusion-weighted images using higher-order information provided by fibre orientation distributions (FODs) computed using spherical deconvolution. AFD has the potential to provide specific information regarding differences between populations by identifying not only the location, but also the orientations along which differences exist. In this work, analytical and numerical Monte-Carlo simulations are used to support the use of the FOD amplitude as a quantitative measure (i.e. AFD) for population and longitudinal analysis. To perform robust voxel-based analysis of AFD, we present and evaluate a novel method to modulate the FOD to account for changes in fibre bundle cross-sectional area that occur during spatial normalisation. We then describe a novel approach for statistical analysis of AFD that uses cluster-based inference of differences extended throughout space and orientation. Finally, we demonstrate the capability of the proposed method by performing voxel-based AFD comparisons between a group of Motor Neurone Disease patients and healthy control subjects. A significant decrease in AFD was detected along voxels and orientations corresponding to both the corticospinal tract and corpus callosal fibres that connect the primary motor cortices. In addition to corroborating previous findings in MND, this study demonstrates the clear advantage of using this type of analysis by identifying differences along single fibre bundles in regions containing multiple fibre populations.

Effects of gender in amyotrophic lateral sclerosis.

BACKGROUND There is evidence that amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is more common in men than in women and that gender influences the clinical features of the disease. The causes of this are unknown. OBJECTIVE This review examines the gender differences that are found in ALS and postulates reasons for these differences. METHODS A literature review of PubMed (with no date limits) was performed to find information about gender differences in the incidence, prevalence, and clinical features of ALS, using the search terms ALS or MND and gender or sex, ALS prevalence, and SOD1 mice and gender. Articles were reviewed for information about gender differences, together with other articles that were already known to the authors. RESULTS The incidence and prevalence of ALS are greater in men than in women. This gender difference is seen in large studies that included all ALS patients (sporadic and familial), but is not seen when familial ALS is studied independently. Men predominate in the younger age groups of patients with ALS. Sporadic ALS has different clinical features in men and women, with men having a greater likelihood of onset in the spinal regions, and women tending to have onset in the bulbar region. Gender appears to have no clear effect on survival. In animals with superoxide dismutase 1 (sod1) mutations, sex does affect the clinical course of disease, with earlier onset in males. Possible reasons for the differences in ALS between men and women include different exposures to environmental toxins, different biological responses to exogenous toxins, and possibly underlying differences between the male and female nervous systems and different abilities to repair damage. CONCLUSIONS There is a complex interaction between gender and clinical phenotypes in ALS. Understanding the causes of the gender differences could give clues to processes that modify the disease.

Impact of Premorbid Undernutrition on Outcome in Stroke Patients

Background and Purpose— To assess the prevalence of premorbid undernutrition and its impact on outcomes 1 month after stroke. Methods— The study recruited from consecutive stroke admissions during a 10-month period. Premorbid nutritional status (using the subjective global assessment [SGA]), premorbid functioning (modified Rankin scale [MRS]), and stroke severity (National Institutes of Health Stroke Scale [NIHSS] score) were assessed at admission. The associations between premorbid nutritional status, poor outcome (defined as MRS ≥3), and mortality were examined before and after adjustment for confounding variables, including age, gender, stroke risk factors, stroke severity, and admission serum albumin. Results— Thirty of 185 patients were assessed as having undernutrition at admission. Significant unadjusted associations were observed between undernutrition and poor outcome (odds ratio [OR], 3.4; 95% CI, 1.3 to 8.7; P =0.01), and mortality (OR, 3.1, 95% CI, 1.3 to 7.7; P =0.02) at 1 month. NIHSS, age, and premorbid MRS were also significantly associated with poor outcomes. After adjustment for these factors, the effect size of associations remained important but not significant (poor outcome: OR, 2.4; 95% CI, 0.7 to 9.0, P =0.18; mortality: OR, 3.2; 95% CI, 1.0 to 10.4, P =0.05). Conclusions— Premorbid undernutrition, as assessed using the SGA, appears to be an independent predictor of poor stroke outcome. Stroke prevention strategies should target undernutrition in the population at risk for stroke to improve outcomes.

Ischemic Stroke and Transient Ischemic Attack After Head and Neck Radiotherapy: A Review

Background and Purpose— Cerebrovascular disease can complicate head and neck radiotherapy and result in transient ischemic attack and ischemic stroke. Although the incidence of radiation vasculopathy is predicted to rise with improvements in median cancer survival, the pathogenesis, natural history, and management of the disease are ill defined. Methods— We examined studies on the epidemiology, imaging, pathogenesis, and management of medium- and large-artery intra- and extra-cranial disease after head and neck radiotherapy. Controlled prospective trials and larger retrospective trials from the last 30 years were prioritized. Results— The relative risk of transient ischemic attack or ischemic stroke is at least doubled by head and neck radiotherapy. Chronic radiation vasculopathy affecting medium and large intra- and extra-cranial arteries is characterized by increasing rates of hemodynamically significant stenosis with time from radiotherapy. Disease expression is the likely consequence of the combined radiation insult to the intima-media (accelerating atherosclerosis) and to the adventitia (injuring the vasa vasorum). Optimal medical treatment is not established. Carotid endarterectomy is confounded by the need to operate across scarred tissue planes, whereas carotid stenting procedures have resulted in high restenosis rates. Conclusions— Head and neck radiotherapy significantly increases the risk of transient ischemic attack and ischemic stroke. Evidence-based guidelines for the management of asymptomatic and symptomatic (medium- and large-artery) radiation vasculopathy are lacking. Long-term prospective studies remain a priority, as the incidence of the problem is anticipated to rise with improvements in postradiotherapy patient survival.

Nonpharmacological treatment, fludrocortisone, and domperidone for orthostatic hypotension in Parkinson's disease.

There is limited evidence for the treatment of orthostatic hypotension in idiopathic Parkinsons disease. The objective of this study was to determine the efficacy of three treatments (nonpharmacological therapy, fludrocortisone, and domperidone). Phase I assessed the compliance, safety, and efficacy of nonpharmacological measures. Phase II was a double‐blind randomized controlled crossover trial of the two medications. Primary outcome measures consisted of the orthostatic domain of the Composite Autonomic Symptom Scale (COMPASS‐OD), a clinical global impression of change (CGI), and postural blood pressure testing via bedside sphygmomanometry (Phase I) or tilt table testing (Phase II). For the 17 patients studied, nonpharmacological therapy did not significantly alter any outcome measure. Both medications improved the CGI and COMPASS‐OD scores. There was a trend towards reduced blood pressure drop on tilt table testing, with domperidone having a greater effect.

The role of immune and inflammatory mechanisms in ALS

Amyotrophic lateral sclerosis (ALS) is a severe progressive neurodegenerative disease. The cause is unknown, but genetic abnormalities have been identified in subjects with familial ALS and also in subjects with sporadic ALS. Environmental factors such as occupational exposure have been shown to be risk factors for the development of ALS. Patients differ in their clinical features and differ in the clinical course of disease. Immune abnormalities have been found in the central nervous system by pathological studies and also in the blood and CSF of subjects with ALS. Inflammation and immune abnormalities are also found in animals with a model of ALS due to mutations in the SOD1 gene. Previously it has been considered that immune abnormalities might contribute to the pathogenesis of disease. However more recently it has become apparent that an immune response can occur as a response to damage to the nervous system and this can be protective.

The Occurrence of Autoimmune Diseases in Patients with Multiple Sclerosis and Their Families

The aims of this study were to determine whether the occurrence of autoimmune diseases is increased in patients with multiple sclerosis (MS) and their families and whether this is influenced by the type of MS. We conducted a case-control study using a questionnaire design to determine whether the prevalence of 11 autoimmune diseases is increased in patients with MS and their first-degree relatives compared to a random population control group and their first-degree relatives. We found that the total combined prevalence of the 11 autoimmune diseases was higher in the MS patients than in the controls, with an odds ratio of 1.7 (95% confidence interval 0.9-3.2; P = 0.10) increasing to 1.9 (1.0-3.5; P = 0.05) after adjusting for age. For persons aged under 60 years, the odds ratio was 2.3 (1.1-4.6). We also found that there was a significant increase in the total combined prevalence of the autoimmune diseases in the first-degree relatives of MS patients compared to the first-degree relatives of the control group (P = 0.003, odds ratio 2.2, confidence interval 1.3-3.7). Patients with primary progressive MS did not differ from patients with relapsing-remitting or secondary progressive MS in the personal or familial occurrence of autoimmune disease. In conclusion, although there were sources of possible bias, this study suggests that individuals with MS have a genetic predisposition to autoimmunity in general.

The effect of ageing on human lymphocyte subsets: comparison of males and females

BackgroundThere is reported to be a decline in immune function and an alteration in the frequency of circulating lymphocytes with advancing age. There are also differences in ageing and lifespan between males and females. We performed this study to see if there were differences between males and females in the frequency of the different lymphocyte subsets with age.ResultsUsing flow cytometry we have examined different populations of peripheral blood leukocytes purified from healthy subjects with age ranging from the third to the tenth decade. We used linear regression analysis to determine if there is a linear relationship between age and cell frequencies. For the whole group, we find that with age there is a significant decline in the percentage of naïve T cells and CD8+ T cells, and an increase in the percentage of effector memory cells, CD4+foxp3+ T cells and NK cells. For all cells where there was an effect of ageing, the slope of the curve was greater for men than for women and this was statistically significant for CD8+αβ+ T cells and CD3+CD45RA-CCR7- effector memory cells. There was also a difference for naïve cells but this was not significant.ConclusionThe cause of the change in percentage of lymphocyte subsets with age, and the different effects on males and females is not fully understood but warrants further study.

Posterior leukoencephalopathy following intrathecal chemotherapy with MRA-documented vasospasm

Posterior leukoencephalopathy syndromes have been reported with hypertension, and immunosuppressive and chemotherapy agents. Cerebral vasospasm on MR angiography (MRA) has been noted in cases due to eclampsia. The authors report a case of Balint syndrome with irreversible posterior leukoencephalopathy on MRI following intrathecal methotrexate and cytarabine. Hypertension was not present. Diffuse, reversible arterial irregularities consistent with vasospasm were present on MRA during the acute illness.