CD4+CD28− lymphocytes and ischaemic stroke. Part I: CD4+CD28− lymphocytes and common carotid artery intima-media thickness

Background and purposeMore and more data point to the involvement of the CD4⁺CD28^? lymphocyte subpopulation in the pathogenesis of ischaemic stroke. This paper attempts to answer the question of whether an increase in the percentage of CD4⁺CD28^? lymphocytes in the blood may be associated with carotid artery intima-media thickness (IMT).Material and methodsThe study involved a group of 109 patients, aged 45 to 65 years, including 42 patients with first-ever ischaemic stroke, experiencing symptoms resulting from disturbances of the anterior area of cerebral circulation, arterial hypertension and/or type 2 diabetes mellitus (group 1). Group 2 consisted of 34 patients with above-mentioned risk factors but without ischaemic stroke. The control group comprised 33 healthy individuals. Distribution of sex and mean age was comparable. The IMT of carotid arteries was measured by ultrasonography. Flow cytometry was applied to determine the percentage of CD4⁺CD28^? lymphocytes in the peripheral blood.ResultsThe IMT was significantly greater in patients with stroke than in patients without stroke. No significant correlation was found between the proportion of CD4⁺CD28^? lymphocytes in the blood and the IMT of carotid arteries.ConclusionsThe significant proportion of CD4⁺CD28^? lymphocytes in patients with ischaemic stroke points to the involvement of the cells in the pathogenesis of stroke. The CD4⁺CD28^? lymphocytes are not involved in the pathomechanism of common carotid arteries IMT thickening in this group of patients.     

Severe ipsilateral carotid stenosis and middle cerebral artery disease in lacunar ischaemic stroke: innocent bystanders?

Objectives Lacunar infarcts are thought to be mostly due to intracranial small vessel disease. Therefore, when a stroke patient with a relevant lacunar infarct does have severe ipsilateral internal carotid artery (ICA) or middle cerebral artery (MCA) disease, it is unclear whether the arterial disease is causative or coincidental. If causative, we would expect ICA/MCA disease to be more severe on the symptomatic side than on the asymptomatic side. Therefore, our aim was to compare the severity of ipsilateral with contralateral ICA and MCA disease in patients with lacunar ischaemic stroke. Methods We studied 259 inpatients and outpatients with a recent lacunar ischaemic stroke and no other prior stroke. We used carotid Duplex ultrasound and transcranial Doppler (TCD) ultrasound to identify ICA and MCA disease, and compared our results with previously published data. Results In our study, there was no difference between the severity of ipsilateral and contralateral ICA stenosis within individuals (median difference 0 %, Wilcoxon paired data p=0.24, comparing severity of ipsilateral and contralateral stenosis). The overall prevalence of severe ipsilateral stenosis was 5 %, and the prevalence of severe contralateral stenosis was 4 % (OR 1.6, 95 % CI 0.6, 4.8). There was no difference in the prevalence of ipsilateral and contralateral MCA disease. A systematic review of the other available studies strengthened this conclusion. Conclusion Carotid stenosis in patients with a lacunar ischaemic stroke may be coincidental. Further studies are required to elucidate the causes of lacunar stroke, and to evaluate the role of carotid endarterectomy. Received: 24 February 2001, Received in revised form: 15 June 2001, Accepted: 3 July 2001     

Coexistence of external carotid artery embolus and internal carotid artery occlusion in acute ischemic stroke: An indicator of cardioembolic etiology?

ObjectivesThis study aims to evaluate whether the presence of an external carotid artery embolism accompanying internal carotid artery occlusion may contribute to identifying the etiology of internal carotid artery occlusion in the early period.Material and methodsThe presence of external carotid artery embolism was evaluated in 117 patients who were adjudicated for internal carotid artery occlusion based on digital subtraction angiography images.ResultsEmbolus in the external carotid artery was detected in 8 (6.8%) of the 117 patients with internal carotid artery occlusion (7 (87.5%) patients were found to have tandem and 1 (12.5%) patient had carotid T occlusion). In all of these patients, the thrombus was of embolic origin. Evaluation of the etiology revealed cardioembolic etiology in 4 patients and dissection in 1 patient, and the cause could not be determined in the remaining 3 patients. Patients with external carotid artery embolism accompanying an internal carotid artery occlusion had significantly higher The National Institutes of Health Stroke Scale scores at admission and significantly lower recanalization success compared to those without external carotid artery embolism (p = 0.009, p = 0.01). In the comparison of prognosis, poorer prognosis was observed in those with external carotid artery embolism, although without a statistically significant difference (p = 0.07).ConclusionsThis study observed that the etiology was mostly embolic in patients with external carotid artery embolism accompanying an internal carotid artery occlusion, most of whom were found to have tandem embolic occlusion, and cardiac origin appeared to be the prominent etiology of stroke.     

MMP-9 and/or TIMP as predictors of ischaemic stroke in patients with symptomatic and asymptomatic atherosclerotic stenosis of carotid artery treated by stenting or endarterectomy – A review

We still lack an optimal tool to predict ischaemic stroke in patients with symptomatic and asymptomatic carotid stenosis (CS). It has already been shown that patients at increased risk of ischaemic stroke can be identified based on the elevated plasma levels of metalloproteinases (MMPs) and reduced activity tissue inhibitor of metalloproteinase (TIMP). There are few studies presenting the role of MMP-9 and TIMP in ischaemic stroke both in patients with symptomatic and asymptomatic CS treated with stenting or endarterectomy, however we have not found any published review summarizing the role of abovementioned markers. MEDLINE was accessed via Pub Med, and searched for published studies that analyzed MMP-9 and TIMP levels in patients with asymptomatic and symptomatic internal carotid stenosis and/or examined these parameters as potential risk markers for ischaemic stroke. A total of 13 articles documenting the outcomes of patients with symptomatic or asymptomatic carotid stenosis treated by carotid stenting or endarterectomy, were analyzed. Statistically significant differences in the levels of MMP-9 and/or TIMP in patients with symptomatic and asymptomatic CS have been reported. Also the concentrations of MMP-9 and TIMP in CS patients subjected to stenting or endarterectomy were higher than in baseline group. Moreover higher levels of MMP-9 and decreased TIMP was reported to be associated with the risk of restenosis. This systematic review shows that available evidence regarding the dynamics of MMP-9 and TIMP levels may be a predictor of cerebrovascular events in both symptomatic and asymptomatic carotid stenosis in patients treated with stenting or endarterectomy.     

Cerebral revascularization with superficial temporal – middle cerebral artery anastomosis for complete carotid occlusion: An emerging modality for preventing recurrent stroke

Complete long segment carotid occlusion presents a treatment challenge. These patients cannot be managed adequately by endarterectomy or stenting. Despite best medical management, many continue to develop recurrent strokes. In this select group of patients, there may be role for flow augmentation techniques like superficial temporal-middle cerebral artery bypass. We report a patient who was thus successfully treated and remains asymptomatic. The relevant literature is reviewed.Key Words: Extra cranial-intracranial bypass, recurrent stroke, superficial temporal - middle cerebral artery bypass, total carotid occlusion     

Prevalence of and risk factors associated with carotid artery stenosis: the Troms? Study.

BACKGROUND AND PURPOSE: To assess prevalence, distribution, ultrasound characteristics and determinants of carotid artery stenosis in a large, population-based study of both women and men. METHODS: A total of 6,727 persons aged 25-84 years were screened for extracranial stenosis with Duplex ultrasound of the right carotid artery. Risk factors were compared in 225 persons with stenosis and 5,514 persons without. RESULTS: The prevalence of carotid stenosis was higher in men than in women, where 3.8% (95% CI, 3.2-4.6%) had carotid stenosis, compared to 2.7% (95% CI, 2.2-3.3%) in women (p = 0.001). The prevalence gradually increased by age in both genders. Cholesterol, HDL cholesterol, fibrinogen, systolic blood pressure levels and current smoking were independently associated with carotid artery stenosis in both women and men. The presence of carotid stenosis was significantly associated with a history of cerebrovascular disease, coronary heart disease and peripheral artery disease. For each 10% increase in the degree of carotid stenosis, the risk of having had a cerebrovascular event increased by 26%. CONCLUSIONS: The prevalence of carotid stenosis in the general population, as measured by ultrasound, is low. Age, male gender, smoking, total cholesterol, HDL cholesterol (inverse), fibrinogen and systolic blood pressure are all independent predictors of carotid artery stenosis.     

Asymptomatic carotid artery stenosis: past, present and future. How to improve patient selection?

BACKGROUND: The role of carotid endarterectomy (CEA) for asymptomatic carotid artery stenosis (aCAS) remains a matter of debate. It seems that not only the degree of stenosis, but also other factors have to be taken in account to improve patient selection and increase the benefit of CEA for aCAS. METHODS AND RESULTS: The literature pertaining aCAS was reviewed in order to describe the natural history, risk of stroke and benefit of CEA for patients with aCAS in regard to several factors. CONCLUSION: The benefit of CEA for aCAS is low. Current factors influencing the indication for CEA are severity of stenosis, age, contralateral disease, stenosis progression to >80%, gender, concomitant operations and life expectancy. To improve patient selection investigations will concentrate on plaque characteristics and instability and cerebral hemodynamics and metabolism.     

Relationship between circulating CD4+ T lymphocytes and cognitive impairment in patients with Parkinson’s disease

IntroductionParkinson’s disease (PD) is characterized by loss of dopaminergic neurons. Neuroinflammation may represent an important factor in the pathophysiology of PD and recent findings indicate that PD patients present a pro-inflammatory peripheral profile of CD4+ T lymphocytes, which may correlate with motor disability. However, no data are currently available on the relationship between CD4+ T lymphocytes and cognitive function in PD.The aim of our study is to evaluate the relationship between cognitive profile and circulating CD4+ T lymphocyte subsets in PD patients.MethodsPD patients underwent blood withdrawal and CD4+ T lymphocyte subpopulations, including CD4+ T naïve and memory cells, Th1, Th2, Th17, Th1/17 and T regulatory (Treg) cells were evaluated by flow cytometry. Cognitive evaluation was performed using Addenbrooke Cognitive Examination (ACE-R).Results43 consecutive PD patients (31 males; age [mean ± SD]: 68.9 ± 8.4 years) were enrolled. 14/43 (32.6%) were drug naïve. Based on the ACE-R score, patients were divided in two groups using defined cutoff values. In comparison to patients with normal cognitive profile, patients with cognitive impairment had a higher number of circulating lymphocytes. Moreover, drug naïve patients with a worse cognitive outcome had a lower number of resting Treg and higher number of activated Treg. Furthermore, we found a correlation between pro-inflammatory peripheral immune phenotype and worse cognitive outcome in the ACE-R total and sub-items scores.ConclusionsIn our cohort of PD patients, cognitive impairment was associated with higher number of circulating lymphocytes, and – at least in drug naïve patients – with dysregulation of the Treg compartment. Further studies are needed to assess whether and to what extent peripheral immunity mechanistically contributes to cognitive decline in PD.     

Low risk of ischemic stroke in patients with reduced internal carotid artery lumen diameter distal to severe symptomatic carotid stenosis: cerebral protection due to low poststenotic flow? On behalf of the European Carotid Surgery Trialists' Collaborative Group

BACKGROUND AND PURPOSE: Patients with recently symptomatic severe carotid stenosis have a high risk of ischemic stroke on medical treatment. The main mechanism of stroke appears to be plaque surface thrombus formation and distal embolism. It is unclear to what extent reduction in blood flow across the stenosis, and the consequent reduction in cerebral perfusion pressure, is also important. Angiographic indices of reduced cerebral perfusion may identify patients at a particularly high risk of stroke who require urgent endarterectomy. The most direct angiographic correlate of poststenotic perfusion pressure is the degree of narrowing of the distal internal carotid artery (ICA) lumen. We sought to develop criteria for the definition of poststenotic narrowing of the ICA and to determine the effect of this and other angiographic characteristics likely to be associated with reduced cerebral perfusion on the risk of ipsilateral ischemic stroke in patients with recently symptomatic carotid stenosis. METHODS: We studied the carotid angiograms of 3007 patients in the European Carotid Surgery Trial. Poststenotic narrowing of the ICA was defined with use of the ratio of the lumen diameter of the ICA to that of the common carotid artery (CCA). The normal range of the ICA/CCA ratio was defined in 2966 symptomatic or contralateral carotid arteries with 0% to 49% stenosis. Arteries with 70% to 99% symptomatic stenosis and an ICA/CCA ratio below this range were categorized as narrowed. We related the presence of narrowing and other angiographic characteristics to the risk of ipsilateral ischemic stroke on medical treatment. RESULTS: An assessment of the ICA/CCA ratio had good interobserver reproducibility. Poststenotic narrowing of the ICA was defined as an ICA/CCA ratio of <0.42. The 5-year risk of ipsilateral carotid territory ischemic stroke on medical treatment was 8% in patients with 70% to 99% stenosis and narrowing of the ICA versus 25% in patients without narrowing (log rank test, P=0.02). This difference remained after correction for other clinical and angiographic variables (hazard ratio 0.40, 95% CI 0.17 to 0.94, P=0. 03). The other angiographic characteristics did not predict stroke. CONCLUSIONS: Poststenotic narrowing of the ICA was associated with a low risk of stroke on medical treatment. This suggests that low flow alone is not usually sufficient to cause ischemic stroke distal to symptomatic carotid stenosis. Poststenotic narrowing may be protective because blood flow distal to the stenosis is insufficient to carry emboli to the brain.     

European clinical guidelines for Tourette syndrome and other tic disorders—version 2.0. Part II: psychological interventions

Part II of the European clinical guidelines for Tourette syndrome and other tic disorders (ECAP journal, 2011) provides updated information and recommendations for psychological interventions for individuals with tic disorders, created by a working group of the European Society for the Study of Tourette Syndrome (ESSTS). A systematic literature search was conducted to obtain original studies of psychological interventions for tic disorders, published since the initial European clinical guidelines were issued. Relevant studies were identified using computerized searches of the MEDLINE and PsycINFO databases for the years 2011–2019 and a manual search for the years 2019–2021. Based on clinical consensus, psychoeducation is recommended as an initial intervention regardless of symptom severity. According to a systematic literature search, most evidence was found for Habit Reversal Training (HRT), primarily the expanded package Comprehensive Behavioral Intervention for Tics (CBIT). Evidence was also found for Exposure and Response Prevention (ERP), but to a lesser degree of certainty than HRT/CBIT due to fewer studies. Currently, cognitive interventions and third-wave interventions are not recommended as stand-alone treatments for tic disorders. Several novel treatment delivery formats are currently being evaluated, of which videoconference delivery of HRT/CBIT has the most evidence to date. To summarize, when psychoeducation alone is insufficient, both HRT/CBIT and ERP are recommended as first-line interventions for tic disorders. As part of the development of the clinical guidelines, a survey is reported from ESSTS members and other tic disorder experts on preference, use and availability of psychological interventions for tic disorders.

     

Expression of transforming growth factor-β1, 2, 3 isoforms and type I and II receptors in acute focal cerebral ischemia: an immunohistochemical study in rat after transient and permanent occlusion of middle cerebral artery

Transforming growth factor beta (TGF-β) is involved in the modulation of cell growth, differentiation and repair following injury of various organs. Previous studies on human autopsy material have indicated that TGF-β isoforms -β1, -β2 and -β3, and TGF-β receptor type I are expressed in various cells of necrotizing brain lesions like infarction and abscess. The present immunohistochemical study was designed to investigate changes that may occur with regard to TGF-β and its receptors type I and II in a rat model of focal brain ischemia induced by transient or permanent occlusion of the middle cerebral artery. Our findings indicate that at days 1 and 3 following such transient and permanent ischemia there is an up-regulation of TGF-β isoforms -β1, -β2 and -β3, and TGF-β receptor types I and II mainly in the perifocal neurons, reactive astroglial cells, endothelial cells and macrophages. Received: 20 May 1998 / Revised: 14 August, 2 November 1998 / Accepted: 3 November 1998     

Doublecortin expression in CD8+ T-cells and microglia at sites of amyloid-β plaques: A potential role in shaping plaque pathology?

Introduction

One characteristic of Alzheimer's disease is the formation of amyloid-β plaques, which are typically linked to neuroinflammation and surrounded by inflammatory cells such as microglia and infiltrating immune cells.

Classification of child stuttering: Part II. Persistent late onset male stuttering,and treatment issues for persistent stutterers-psychotherapy or speech therapy,or both?

This paper is the second of a two-part study. Part I of this study presented child stuttering as a psychologically heterogeneous population so classified: transient developmental, neurogenic acquired; and persistent stuttering. In Part II, parental patterns, ego functioning and psychodynamic etiological factors are described for a group of 16 persistent late onset male stutterers. Specific psychotherapeutic approaches for the persistent late onset male stutterer highlights the need for the exposition and resolution of a partial negative oedipal fixation as well as the acknowledgement and relinquishment of significant narcissistic claims whose awareness is defended against by the use of the stuttering symptom. Specific psychotherapeutic techniques are described for all male and female persistent stutterers. The issue of psychotherapy versus speech therapy is addressed. The need for ongoing collaboration between child psychiatrist and speech pathologist is multiple: to address when a child psychiatry evaluation is needed, in order for the heterogeneity of stuttering to be recognized, and for further research to develop.Part I of Classification of Child Stuttering appears in Vol. 12, No. 4 of thisJournal     

Effect of IFN-ß therapy on the frequency and function of CD4+CD25+ regulatory T cells and Foxp3 gene expression in relapsing–remitting multiple sclerosis (RRMS): A preliminary study

Interferon-ß (IFN-ß) is an immunomodulatory drug of choice to control relapsing–remitting multiple sclerosis (RR-MS), although its function is still unclear. A reduced suppressive function of CD4⁺CD25⁺ regulatory T cells (T_reg) has been shown in RR-MS patients. In this study, to understand the effect of IFN-ß on CD4⁺CD25⁺ regulatory T cells, we analyzed the frequency and function of these cells and Foxp3 gene expression before and after treatment.We evaluated the frequency and function of CD4⁺CD25⁺Foxp3⁺ regulatory T cells by flow cytometry and co-culture inhibition test respectively and gene expression of Foxp3 by real-time PCR in a longitudinal follow-up study in 18 relapsing–remitting MS patients. Our data revealed that IFN-ß significantly improved frequency and suppressive function of T_reg cells (P < 0.05) without any significant effect on gene expression of Foxp3 after 6 months. The results of the present study indicate that IFN-ß therapy in some of patients with RR-MS may restore function of regulatory T cells and control the unchecked immune cascade activity. Larger longitudinal studies on more MS patients are required to confirm our findings.