Cognitive and functional impairments in ischemic stroke patients with concurrent small vessel and large artery disease

Background and purpose

Concurrent small vessel, intracranial and extracranial large artery disease (SLAD) is common in Asian but its impact on cognitive and functional outcomes is unclear. We aimed to evaluate the clinical, cognitive and functional outcomes in ischemic stroke patients with SLAD.

Methods

Chinese ischemic stroke patients with diffuse white matter lesions (WMLs) were recruited as part of the VITATOPS Trial. They were studied with MRI and MRA of brain. Various neuropsychiatric batteries were used to assess the cognitive functions.

Results

Totally 97 patients with acute ischemic stroke and diffuse WMLs were included, of whom 44 (45%) had SLAD. Patients with SLAD had lower Mini Mental State Examination (MMSE) when compared with the patients without SLAD. They had more behavioral symptoms and caused more stress in caregivers as assessed by the Neuropsychiatric Inventory (NPI). Multivariate regression analysis showed SLAD contributed significantly to MMSE, NPI Patient (NPI P) and NPI Care Giver (NPI CG). Among 44 patients with SLAD, 30 (68%) had severe cognitive impairment. They were older and less educated. They had more diabetes and poorer performance in neuropsychiatric tests including Mattis Dementia Rating Scale Initiation/Perseveration subset (MDRS I/P) and Clinical Dementia Rating (CDR). They also had poorer functional outcomes as assessed by Barthel Index (BI) and Instrumental activities of daily living (IADL).

Conclusions

This was the first MRA-based study to take into consideration the clinical, cognitive and functional outcomes in ischemic stroke patients with SLAD. Patients with SLAD had poorer cognitive and functional outcomes when compared to patients without SLAD.     

Recovery of submaximal upper limb force production is correlated with better arm position control and motor impairment early after a stroke

Objective

This study determined whether recovery of upper limb position control using submaximal force production correlates with an improvement in functional arm impairment during early recovery from stroke.

Methods

Ten consecutive inpatients were recruited from a stroke unit. Each patient was in early recovery (<8 weeks post-lesion) from their first ever stroke. Evaluations of submaximal continuous force production and position control, maximal force production at the shoulder and a clinical outcome measure of motor impairment (Fugl-Meyer score; FM) were performed 20 days post-stroke as a baseline and then once a week for the following four weeks.

Results

Submaximal force production and its modulation during a position-holding task improved in early recovery after stroke, whereas maximal force production did not. Better modulation of submaximal force production enabled improved arm position control which was significantly correlated to the changes in FM score of motor impairment during recovery.

Conclusions

This study demonstrated that improvement in submaximal force modulation can operate as a mechanism enabling better motor behaviour such as arm position control during early recovery from a stroke.

Significance

Future rehabilitation strategies may benefit from adding submaximal force development and modulation to early interventions after stroke.     

Coagulation factor XIII activation peptide and subunit levels in patients with acute ischaemic stroke: A pilot study

Introduction

We have recently shown that FXIII activation peptide (AP-FXIII) can be measured in plasma. The objective of this pilot study was to investigate for the first time if AP-FXIII can be detected in plasma from patients with acute ischaemic stroke.

Materials and methods

We included 66 patients with acute ischaemic stroke admitted between 1 and 7 hours after the onset of clinical symptoms. We collected plasma samples upon admission and on the two following days and measured AP-FXIII and subunit levels by ELISA. Clinical stroke severity was assessed by NIHSS stroke score.

Results

AP-FXIII could be detected in 34 patients upon admission (range 0.2-26.3 ng/ml), on day 1 in 15 patients (0.2-10.4 ng/ml), and on day 2 in 11 patients (0.1-15.1 ng/ml. AP-FXIII was higher in patients with severe stroke. Lower AP-FXIII levels upon admission were associated with clinical improvement. FXIII-A and FXIII-B subunit levels decreased significantly from day 0 to day 1.

Conclusions

For the first time, we detected AP-FXIII in patients upon an acute thrombotic event. The decrease in FXIII subunit levels during acute ischaemic stroke is evidence for ongoing coagulation activity and FXIII consumption. Our results suggest that FXIII activation and concomitant AP-FXIII release might be associated with an unfavourable short-term clinical outcome. Larger studies are needed to further investigate whether AP-FXIII might serve as a diagnostic and/or prognostic marker for acute thrombotic diseases.     

Affect recognition as an independent social function determinant in schizophrenia

Introduction

Facial affect recognition deficits may represent specific deficits and contribute to social dysfunction in patients with schizophrenia. Whether their impacts on social dysfunction are independent to those caused by deficits in basic neurocognition and clinical symptoms needs to be further delineated.

Method

Association patterns between affect recognition and basic neurocognitive abilities in 40 acute and 33 stable patients with schizophrenia were compared to explore whether their interrelationships changed across clinical stages. The independent contribution of affect recognition deficits to social dysfunction was explored by multivariate models controlling for general intellectual ability, basic neurocognition, and clinical symptoms.

Results

Affect recognition deficits were associated with social role performances, self-care, and contributed independently to global social functioning in stable patients but not in acute patients. Conversely, affect recognition deficits were associated with impaired basic neurocognitions in acute patients but not in stable patients.

Conclusion

In stabilized community patients with schizophrenia, affect recognition deficits were relatively independent to basic neurocognition and had significant social functional consequences.     

Levels and value of platelet activation markers in different subtypes of acute non-cardio-embolic ischemic stroke

Introduction

Platelet activation and its interaction with leukocytes are important in the pathophysiology of ischemic stroke. This study aimed to evaluate the value of platelet activation and platelet-leukocyte interaction in different subtypes of acute, non-cardio-embolic ischemic stroke.

Methods

Fifty-four patients with acute, non-cardio-embolic ischemic stroke, including 32 small-vessel and 22 large-vessel diseases, were evaluated. Platelet activation markers (CD62P, CD63, and CD40L) and platelet-leukocyte interaction were measured by flow cytometry at different time points (< 48 hours and Days 7, 30, and 90 post-ischemic stroke). Markers were also evaluated in 28 other stroke patients in the convalescent stage (3 to 9 months after acute stroke) and in 28 control subjects.

Results

Patients with ischemic stroke had significantly increased circulating CD62P, CD63, platelet-monocyte interaction, and platelet-lymphocyte interaction in the acute stage compared with the convalescent stage and control groups. Levels of CD62P and CD63 were significantly higher in the large-vessel disease group than in the small-vessel disease group, and differences in CD62P were significant even at one month. The CD40L level in the poor outcome group was significantly higher than that in the good outcome group. Stroke patients with diabetes mellitus and large-vessel disease were associated with poor outcome.

Conclusions

Patients with large-vessel cerebral infarction elicit higher platelet activation and platelet-leukocyte interaction compared to small-vessel infarction. Further large scale trials are warranted to evaluate the relationship between platelet activation markers and outcome in stroke patients under different anti-platelet therapies, and to clarify optimal treatment.     

Aspirin treatment influences platelet-related inflammatory biomarkers in healthy individuals but not in acute stroke patients

Objectives

Platelet-leukocyte aggregation is believed to contribute to acute thrombotic events. While the effect of aspirin on platelet-to-platelet aggregation is well established, the impact of the drug on pro-inflammatory platelet function remains equivocal. Thus we investigated the effect of aspirin on selected platelet-related inflammatory biomarkers in both acute ischaemic stroke patients and healthy volunteers.

Methods

Using five-colour flow cytometry the platelet surface expression of CD62P and CD40L and subpopulations of leukocyte-platelet aggregates were assessed in 63 acute stroke patients and 40 healthy volunteers at baseline and after a 10-day period of aspirin intake at a daily dose of 150 mg. Simultaneously the plasma levels of soluble CD62P and CD40L, serum level of TxB₂, and whole blood impedance platelet aggregation under arachidonic acid (AA) stimulation were investigated.

Results

No differences in values of studied platelet-related inflammatory biomarkers in both resting platelets and those activated with TRAP after 10-day treatment with aspirin were confirmed in stroke subjects. In healthy individuals the resting platelet expression of CD62P, plasma level of soluble CD62P and percentage of circulating monocyte-platelet aggregates were lower after the aspirin intake period (P = 0.009; P = 0.04; P = 0.004, respectively). In both studied groups serum level of TxB₂ and platelet aggregation under AA stimulation were lower than before treatment (P < 0.001).

Conclusion

Despite effective inhibition of COX-1-dependent platelet aggregation, aspirin does not influence the platelet α-granule-derived inflammatory mediators and monocyte-platelet aggregation in acute stroke subjects, although it does in healthy individuals.     

The Influence of Direct Thrombin Inhibitors on the Formation of Platelet-leukocyte Aggregates and Tissue Factor Expression

Introduction

High concentrations of platelet-monocyte aggregates (PMAs) have been found in patients with myocardial infarction (MI). Oral direct thrombin inhibitors (DTIs) are under evaluation as long-term antithrombotic treatment. The aim was to evaluate whether DTIs affect the formation of platelet-leukocyte aggregates, TF expression and procoagulant microparticles (MPs).

Material and Methods

DTIs were added to an experimental whole blood model before platelet activation with thrombin or ADP. The concentrations of PMAs, platelet-granulocyte aggregates (PGAs), the amount of platelets bound per leukocyte and MPs were investigated by flow cytometry. TF mRNA and activity were recorded in all settings. TF activity was evaluated in a MI population treated with or without an oral DTI.

Results

In vitro, thrombin and ADP increased the formation of PMAs and PGAs as well as TF mRNA expression. DTIs reduced the amount platelets bound to monocytes (p = 0.02) and to granulocytes (p = 0.001) upon thrombin stimulation together with a reduction of TF mRNA. In contrast, the ADP-induced formation of PMAs, PGAs and TF mRNA was not affected by the DTIs. Both thrombin and ADP stimulation increased the amount of TF-expressing MPs, which was effectively inhibited by the DTIs (p = 0.02-0.002). In the MI population, the DTI reduced the TF activity (p < 0.001).

Conclusion

DTIs modulate the formation of PMAs, PGAs and the TF production therein. Together with a reduction of procoagulant MPs, these results may contribute to the clinical benefit found of oral DTIs. Targeting different mechanisms in platelet and coagulation activation may be of importance due to the lack of effect of DTIs on ADP-induced platelet-leukocyte aggregates and TF production.     

Computer-based model of epidural motor cortex stimulation: Effects of electrode position and geometry on activation of cortical neurons

Objective

The aim of this study was to determine the effects of electrode placement, geometry, and polarity during epidural cortical stimulation (ECS) on thresholds for direct activation of cortical neurons.

Methods

We used a computational model of epidural electrical stimulation of the motor cortex coupled to compartmental models of cortical neurons.

Results

Thresholds varied with stimulation polarity and neuron position, and neurons deep within the sulci had much larger thresholds than those on the crowns or lips of the gyri. Axons were more excitable than cell bodies or dendrites. Delivering stimulation with the lead placed above or perpendicular to the sulci resulted in substantial stimulation of the gyri adjacent to the target gyrus. Electrode diameter and inter-electrode spacing influenced thresholds and affected the spread of activation in the cortex.

Conclusions

Electrode placement, geometry, and polarity during ECS influence excitation properties of cortical neurons substantially.

Significance

Epidural leads have varying geometries, and in clinical studies of ECS the placement of the lead has been inconsistent. These results provide an improved understanding of the effects of electrode placement, geometry, and polarity on the outcome of ECS and can facilitate the rational implantation and programming of ECS systems.     

Autonomic cardiovascular control and responses to experimental pain stimulation in fibromyalgia syndrome

Objective

This study involves a comprehensive investigation of autonomic cardiovascular regulation in fibromyalgia syndrome (FMS) at rest and during painful stimulation and its association with pain indices.

Methods

In 35 patients and 29 healthy controls, electrocardiography, impedance cardiography, and finger continuous blood pressure measurements were conducted. For the purpose of experimental pain induction, a cold pressor test was applied.

Results

FMS patients showed lower pain threshold and tolerance, as well as higher ratings of pain intensity and unpleasantness on visual analogue scales. Resting stroke volume, myocardial contractility, R-R interval, heart rate variability, and sensitivity of the cardiac baroreflex were reduced in the patients, and increases in stroke volume and myocardial contractility during cold pressor stimulation were less pronounced. In the whole sample as well as in the FMS group, baroreflex sensitivity was inversely associated with subjective pain intensity, and a higher number of baroreflex operations per unit of time predicted higher pain tolerance.

Conclusions

The data suggest impaired autonomic cardiovascular regulation in FMS in terms of reduced sympathetic and parasympathetic influences, as well as blunted sympathetic reactivity to acute stress. The association between baroreflex function and pain experience reflects the pain inhibition mediated by the baroreceptor system. Given the reduced baroreflex sensitivity in FMS, one may assume deficient ascending pain inhibition arising from the cardiovascular system, which may contribute to the exaggerated pain sensitivity of FMS.     

Influence de la structure unité neurovasculaire sur la mise en pratique des recommandations professionnelles

Introduction

Patients who receive care in a dedicated stroke unit are more likely to survive and become independent. Specific guidelines describe evidence-based care practices. We examined the results of a French audit validation campaign to determine whether the presence of a stroke unit had an influence on the implementation of these recommendations.

Methods

Eleven hospital centers volunteered for self-evaluation. Care delivered to patients in the emergency room and in the hospital unit (dedicated stroke unit or not) was assessed with the clinical audit method.

Results

Compared with non-dedicated units, care delivered in stroke units was significantly more compliant with published recommendations. All aspects of acute stroke care were concerned: initial evaluation, acute phase treatment, screening for complications and their treatment, multidisciplinary team coordination, discharge preparation. Care delivered in dedicated stroke units was more reproducible, protocols were more widely used, acute phase risks were better prevented, and acute and postacute care was better coordinated between professionals. A second audit one year later showed increased quality of care in both dedicated and non-dedicated units, with more items improved in the latter.

Conclusion

Although statistical bias cannot be excluded, this study suggests that recommendations are applied better in dedicated stroke units. A second audit showed better compliance with recommendations, especially in non-dedicated units.     

Infarctus cérébral, infection VIH et syphilis méningovasculaire : étude de trois cas

Introduction

Various clinical manifestations can occur in syphilis, especially meningovascular syphilis. We report three cases of ischemic stroke related to meningovascular syphilis and HIV infection.

Case reports

Three men, aged 30, 31 and 41, presented typical neurologic deficit leading to the diagnosis of ischemic stroke. Radiographic investigations showed internal carotid thrombosis in two patients, and a basilar stenosis in the third. CSF analysis and blood samples revealed meningovascular syphilis associated with HIV infection. The other explorations were normal.

Conclusion

Due to the reemergence of syphilis, search for Treponema pallidum infection should be systematic in young stroke victims.     

Cognitive reserve modulates task-induced activations and deactivations in healthy elders, amnestic mild cognitive impairment and mild Alzheimer's disease

Introduction

Cognitive reserve (CR) reflects the capacity of the brain to endure neuropathology in order to minimize clinical manifestations. Previous studies showed that CR modulates the patterns of brain activity in both healthy and clinical populations. In the present study we sought to determine whether reorganizations of functional brain resources linked to CR could already be observed in amnestic mild cognitive impairment (a-MCI) and mild Alzheimer's disease (AD) patients when performing a task corresponding to an unaffected cognitive domain. We further investigated if activity in regions showing task-induced deactivations, usually identified as pertaining to the default-mode network (DMN), was also influenced by CR.

Methods

Fifteen healthy elders, 15 a-MCI and 15 AD patients underwent functional magnetic resonance imaging (fMRI) during a speech comprehension task. Differences in the regression of slopes between CR proxies and blood-oxygen-level dependent (BOLD) signals across clinical groups were investigated for activation and deactivation areas. Correlations between significant fMRI results and a language comprehension test were also computed.

Results

Among a-MCI and AD we observed positive correlations between CR measures and BOLD signals in task-induced activation areas directly processing speech, as well as greater deactivations in regions of the DMN. These relationships were inverted in healthy elders. We found no evidence that these results were mediated by gray matter volumes. Increased activity in left frontal areas and decreased activity in the anterior cingulate were related to better language comprehension in clinical evaluations.

Conclusions

The present findings provide evidence that the neurofunctional reorganizations related to CR among a-MCI and AD patients can be seen even when considering a preserved cognitive domain, being independent of gray matter atrophy. Areas showing both task-induced activations and deactivations are modulated by CR in an opposite manner when considering healthy elders versus patients. Brain reorganizations facilitated by CR may reflect behavioral compensatory mechanisms.     

Thrombolyse intraveineuse par rt-PA des accidents vasculaires cérébraux ischémiques : l’expérience de l’unité neurovasculaire de Nice

Introduction

Intravenous thrombolysis with rt-Pa in stroke has been approved in France since 2002. We report an evaluation of our practice. We have tried to identify predictive factors of dependence and death, and to compare our results with the data of the literature.

Patients and method

All patients treated with intravenous rt-PA within the first 270 min after the stroke onset were included. Univariate, then multivariate analyses were performed to determine the variables influencing the functional outcome at 3 months follow-up, according to a dichotomy established from the modified Rankin scale.

Results

One hundred and forty-two patients were included in this study (mean initial National Institute of Health Stroke Scale [NIHSS]: 15). Fifty percent had a Rankin score higher than 2 at 3 months follow-up. NIHSS above 12, glycemia of at least 120 mg/l, and systolic blood pressure above 160 mmHg at admission were identified as independent predictive factors of poor functional outcome. Less than 4 points decrease of NIHSS proved to be a simple and early predictor of poor functional outcome at 3 months follow-up.

Conclusions

In terms of safety and efficacy the data issuing from the daily activity of our stroke unit are comparable with those of clinical trials.     

Delirium in children and adolescents: A systematic review of the literature

Objectives

The purpose of this study was to collate all works relating to delirium and probable delirium in children and adolescents published since 1980.

Methods

A systematic review of the literature in all languages published between 1980 and March 2009 was conducted.

Results

The literature is limited to small case series and case reports including a total of 217 children or adolescents with definite delirium and a further 136 children and adolescents with “probable delirium.” These articles, in addition to unsystematic reviews, overviews, editorials, journal commentaries, and pertinent book chapters, are discussed in relation to prevalence, predisposing and precipitating factors, phenomenology, residual psychopathology, mortality, management, and prevention of delirium in childhood and adolescence.

Conclusions

Delirium is an important but neglected disorder of childhood associated with significant morbidity and high mortality. Current clinical practice for management is based on slim empirical evidence.     

Where (in the brain) do semantic errors come from?

Background

Semantic errors result from the disruption of access either to semantics or to lexical representations. One way to determine the origins of these errors is to evaluate comprehension of words that elicit semantic errors in naming. We hypothesized that in acute stroke there are different brain regions where dysfunction results in semantic errors in both naming and comprehension versus those with semantic errors in oral naming alone.

Methods

A consecutive series of 196 patients with acute left hemispheric stroke who met inclusion criteria were evaluated with oral naming and spoken word/picture verification tasks and magnetic resonance imaging within 48 h of stroke onset. We evaluated the relationship between tissue dysfunction in 10 pre-specified Brodmann's areas (BA) and the production of coordinate semantic errors resulting from (1) semantic deficits or (2) lexical access deficits.

Results

Semantic errors arising from semantic deficits were most associated with tissue dysfunction/infarct of left BA 22. Semantic errors resulting from lexical access deficits were associated with hypoperfusion/infarct of left BA 37.

Conclusion

Our study shows that semantic errors arising from damage to distinct cognitive processes reflect dysfunction of different brain regions.     

Effects of mobile phone signals over BOLD response while performing a cognitive task

Objective

The aim of this study was to investigate the effects induced by an exposure to a GSM signal (Global System for Mobile Communication) on brain BOLD (blood-oxygen-level dependent) response, as well as its time course while performing a Go-NoGo task.

Methods

Participants were tested twice, once in presence of a “real” exposure to GSM radiofrequency signal and once under a “sham” exposure (placebo condition). BOLD response of active brain areas and reaction times (RTs) while performing the task were measured both before and after the exposure.

Results

RTs to the somatosensory task did not change as a function of exposure (real vs sham) to GSM signal. BOLD results revealed significant activations in inferior parietal lobule, insula, precentral and postcentral gyri associated with Go responses after both ‘‘real’’ and ‘‘sham’’ exposure, whereas no significant effects were observed in the ROI analysis.

Conclusions

The present fMRI study did not detect any brain activity changes by mobile phones. Also RTs in a somatosensory task resulted unaffected.

Significance

No changes in BOLD response have been observed as a consequence of RF-EMFs exposure.     

Apport d’une démarche électroclinique dans le diagnostic de l’épilepsie chez une population de sujets âgés confus

Background

Delusion symptoms often occur in old people; epilepsy is one of the main reasons behind these acute episodes. Current guidelines and recommendations from the Academy of Medicine have proposed a double clinical and electroencephalographic approach. Recently, a working group of French experts has issued an electro-clinical scale. The aim of our study was to compare the usual approach with the new one based on the electro-clinical score.

Method

All EEG requests performed since December 2008 in Bretonneau Hospital for elderly people aged over 75 years for delusion syndromes were retained for this study.

Results

One hundred and fifteen old patients from a geriatric-hospital (age 83.5 ± 6.06 years) were included in this protocol. The classical diagnostic process yielded the diagnosis of epilepsy for 50 subjects. The electro-clinical scale confirmed the diagnosis of epilepsy in 30 patients and ruled it out in 29 patients.

Conclusion

This study underscores the importance of evidence-based medicine for the diagnosis of epilepsy in old people and points out the underuse of the new technical tool, EEG-monitoring, for the management of these patients.     

Patients’ subjective initial response and the outcome of inpatient and day hospital treatment

Objective

This study aimed to establish whether psychiatric patients’ subjective initial response (SIR) to hospital and day hospital treatment predicts outcomes over a one-year follow-up period.

Method

We analysed data from 765 patients who were randomised to acute psychiatric treatment in a hospital or day hospital. SIR was assessed on day 3 after admission. Outcomes were psychiatric symptom levels and social disability at discharge, and at 3 and 12 months after discharge.

Results

After controlling for socio-demographic and clinical characteristics, a more positive SIR was significantly associated with lower symptom levels at discharge and 3 months after discharge and lower social disability at 3 months and 12 months after discharge.

Conclusion

SIR can predict outcomes of complex interventions over a one-year period. Patients’ initial views of acute hospital and day treatment should be elicited and considered as important.     

Effects of acute and chronic sleep deprivation on daytime alertness and cognitive performance of healthy snorers and non-snorers

Background

Respiratory events during sleep usually lead to micro arousals resulting in consecutive daytime sleepiness even in healthy snorers. The present study investigated the evolution of subjective and objective daytime sleepiness and reaction time in healthy snorers submitted to acute and chronic sleep deprivation.

Methods

Objective sleepiness was measured by the MSLT, subjective sleepiness by the Karolinska Sleepiness Scale (KSS), and reaction time (RT) by the Psychomotor Vigilance Test. Mean sleep latencies, KSS scores and performance were analyzed through repeated measures ANOVAs with one between-factor (snorers and non-snorers) and two within-factors (sleep deprivation [baseline, acute, and chronic sleep deprivation] and time-of-day).

Results

The findings reveal that sleep deprivation does not enhance snoring but that, during baseline, objective daytime sleepiness is higher in snorers than in non-snorers (shorter sleep latencies) with no difference in subjective assessments. The effects of acute and chronic sleep deprivation on sleep are similar in both groups, but, after acute sleep deprivation, RT and attentional lapses (RT >500 ms) are higher in snorers. Chronic sleep deprivation produces similar results in both groups.

Conclusion

These results suggest that respiratory efforts may be involved in the increased vulnerability to sleep deprivation of healthy snorers when compared to non-snorers.     

Acute vagus nerve stimulation using different pulse widths produces varying brain effects

Background

Vagus nerve stimulation (VNS) is an approved treatment for epilepsy and has been investigated in clinical trials of depression. Little is known about the relationship of VNS parameters to brain function. Using the interleaved VNS /functional magnetic resonance imaging (fMRI) technique, we tested whether variations of VNS pulse width (PW) would produce different immediate brain activation in a manner consistent with single neuron PW studies.

Methods

Twelve adult patients with major depression, treated with VNS, underwent three consecutive VNS/fMRI scans, each randomly using one of three PWs (130 μs, 250 μs, or 500 μs). The data were analyzed with SPM2.

Results

Global activations induced by PWs 250 and 500 were both significantly greater than that induced by PW 130 but not significantly different from each other. For global deactivation, PWs 130 and 250 were both significantly greater than PW 500 but not significantly different from each other. Regional similarities and differences were also seen with the various PWs.

Conclusions

The data confirm our hypothesis that VNS at PW 500 globally produces no more activation than does PW 250, and PW 130 is insufficient for activation of some regions. These data suggest that PW is an important variable in producing VNS brain effects.