Stroke territory and atherosclerosis in ischemic stroke patients with a history of migraine with aura.

Introduction: The mechanisms subtending the increased stroke risk in migraine with aura (MA) are not fully understood. Our study aims to evaluate if the clinical profile in stroke patients with MA differentiates from those without MA. Methods: We retrieved the prospective registered electronic clinical dossiers of adult patients younger than 60 years with acute ischemic stroke admitted in four hospitals between January 2016 and June 2022. Patients were classified by the history of MA (MA+ and MA-). Results: We identified 851 stroke patients (59 MA+, 6.9%). Compared to MA-, MA+ patients were characterized by younger age (44.0 ± 10.6 vs 50.1 ± 8.2 years), female sex (59.3% vs 29.0%), and affected by cryptogenic (OR 2.594 95% CI 1.483-4.537), and cerebellar stroke (OR 3.218 95% CI 1.657-6.250; p ≤ 0.001 for all comparisons). After adjusting for age and sex, MA+ patients presented less frequently hypertension (OR 0.349 95% CI 0.167-0.470; p=0.005) and dyslipidemia (OR 0.523 95% CI 0.280-0.974; p = 0.041). After adjusting also for risk factors, the MA+ group had less frequently symptomatic large vessel stenosis (OR 0.126 95% CI 0.017-0,924; p = 0.042) and clinical atherosclerosis (OR 0.103 95% CI 0.014-0.761; p = 0.026), while intima-media thickness did not differ (p = 0.395). Discussion: Cryptogenic and cerebellar stroke and fewer vascular risk factors and clinical atherosclerosis seem to characterize stroke patients with MA.

Carotid Artery Plaque Progression: Proposal of a New Predictive Score and Role of Carotid Intima-Media Thickness.

BACKGROUND: We aimed to investigate if the carotid intima-media thickness (IMT) at baseline and the HAD2S score, composed of the sum of single risk factors (hypertension, age ≥ 75 years, diabetes, dyslipidemia, smoking), were predictive of plaque progression. METHODS: We performed a retrospective analysis on real-life prospectively collected data from patients with any detectable carotid plaque at follow up. The plaque score, calculated at baseline (T0) and at a median follow up of 36.6 months (IQR 39.6-34.3) (T3), was defined as 0: no plaque or stenosis < 30%; 1: stenosis in the range 30-49%; 2: in the range 50-69%; 3: in the range 70-99% and 4: occlusion. Carotid IMT was measured at T0 and T3; HAD2S score was calculated at baseline. RESULTS: We included 340 patients with a mean age of 69.9 (9.1) years and 25.3% subjects had plaque progression. Individuals with progression had a median HAD2S score of 3 (1) while those without progression had 2 (1). Patients with progression had a mean baseline IMT of 0.86 (0.17) while those without progression had 0.77 (0.18) (p < 0.0001). A correlation between progression and baseline IMT was found (p = 0.002). CONCLUSION: Baseline IMT could be considered a predictor of progression. Patients with progression had an HAD2S score higher than those without evolution.

Shorter visual aura characterizes young and middle-aged stroke patients with migraine with aura.

OBJECTIVE: To identify the clinical profile and aura characteristics of patients with Migraine with Aura (MwA) having acute cerebral ischemia, we compared stroke phenotype and risk factors in stroke patients with (S+MwA+) or without (S+MwA-) MwA and aura features in MwA patients with (S+MwA+) or without (S-MwA+) stroke. METHODS: In this retrospective multicenter case-control study, we reviewed stroke phenotypes and vascular risk factors in S+MwA+ and S+MwA- patients younger than 60 years and risk factors and aura type, duration, onset age, and the frequency in the previous year in S+MwA+ patients and S-MwA+ subjects matched for age and disease history, investigated for patent foramen ovale (PFO). RESULTS: 539 stroke (7.7% S+MwA+) and 94 S-MwA + patients were enrolled. S+MwA+ patients were younger (p =.0.004) and more frequently presented PFO [OR 4.89 (95% CI 2.12-11.27)], septal interatrial aneurism [OR 2.69 (95% CI 1.15-6.27)] and cryptogenic ischemic stroke (CIS) [OR 6.80 (95% CI 3.26-14.18)] than S+MwA- subjects. Significant atherosclerosis was not detected in S+MwA+ patients. Compared to S-MwA+, S+MwA+ patients were characterized by visual [OR 3.82 (95% CI 1.36-10.66)] and shorter-lasting (20.0 min IQr 13.1 vs 30.0 min IQr 25.0; p < 0.001) aura, and PFO [OR 1.26 (95% CI 1.03-1.54)]. Regression analysis evidenced that only shorter aura duration associated with stroke (p = 0.001). High-risk PFO was equally represented in S+MwA-, S+MwA+, S-MwA+ groups. CONCLUSIONS: Shorter visual aura and CIS characterize MwA patients with stroke. Although more prevalent, PFO can not be considered the main responsible for the increased stroke risk in MwA patients but as a part of a complex multifactorial condition.

Cerebral critical closing pressure and resistance-area product: the influence of dynamic cerebral autoregulation, age and sex.

Instantaneous arterial pressure-flow (or velocity) relationships indicate the existence of a cerebral critical closing pressure (CrCP), with the slope of the relationship expressed by the resistance-area product (RAP). In 194 healthy subjects (20-82 years, 90 female), cerebral blood flow velocity (CBFV, transcranial Doppler), arterial blood pressure (BP, Finapres) and end-tidal CO2 (EtCO2, capnography) were measured continuously for five minutes during spontaneous fluctuations of BP at rest. The dynamic cerebral autoregulation (CA) index (ARI) was extracted with transfer function analysis from the CBFV step response to the BP input and step responses were also obtained for the BP-CrCP and BP-RAP relationships. ARI was shown to decrease with age at a rate of -0.025 units/year in men (p = 0.022), but not in women (p = 0.40). The temporal patterns of the BP-CBFV, BP-CrCP and BP-RAP step responses were strongly influenced by the ARI (p < 0.0001), but not by sex. Age was also a significant determinant of the peak of the CBFV step response and the tail of the RAP response. Whilst the RAP step response pattern is consistent with a myogenic mechanism controlling dynamic CA, further work is needed to explore the potential association of the CrCP step response with the flow-mediated component of autoregulation.

The critical closing pressure contribution to dynamic cerebral autoregulation in humans: influence of arterial partial pressure of CO2.

KEY POINTS: Dynamic cerebral autoregulation (CA) is often expressed by the mean arterial blood pressure (MAP)-cerebral blood flow (CBF) relationship, with little attention given to the dynamic relationship between MAP and cerebrovascular resistance (CVR). In CBF velocity (CBFV) recordings with transcranial Doppler, evidence demonstrates that CVR should be replaced by a combination of a resistance-area product (RAP) with a critical closing pressure (CrCP) parameter, the blood pressure value where CBFV reaches zero due to vessels collapsing. Transfer function analysis of the MAP-CBFV relationship can be extended to the MAP-RAP and MAP-CrCP relationships, to assess their contribution to the dynamic CA response. During normocapnia, both RAP and CrCP make a significant contribution to explaining the MAP-CBFV relationship. Hypercapnia, a surrogate state of depressed CA, leads to marked changes in dynamic CA, that are entirely explained by the CrCP response, without further contribution from RAP in comparison with normocapnia. ABSTRACT: Dynamic cerebral autoregulation (CA) is manifested by changes in the diameter of intra-cerebral vessels, which control cerebrovascular resistance (CVR). We investigated the contribution of critical closing pressure (CrCP), an important determinant of CVR, to explain the cerebral blood flow (CBF) response to a sudden change in mean arterial blood pressure (MAP). In 76 healthy subjects (age range 21-70 years, 36 women), recordings of MAP (Finometer), CBF velocity (CBFV; transcranial Doppler ultrasound), end-tidal CO2 (capnography) and heart rate (ECG) were performed for 5 min at rest (normocapnia) and during hypercapnia induced by breathing 5% CO2 in air. CrCP and the resistance-area product (RAP) were obtained for each cardiac cycle and their dynamic response to a step change in MAP was calculated by means of transfer function analysis. The recovery of the CBFV response, following a step change in MAP, was mainly due to the contribution of RAP during both breathing conditions. However, CrCP made a highly significant contribution during normocapnia (P < 0.0001) and was the sole determinant of changes in the CBFV response, resulting from hypercapnia, which led to a reduction in the autoregulation index from 5.70 ± 1.58 (normocapnia) to 4.14 ± 2.05 (hypercapnia; P < 0.0001). In conclusion, CrCP makes a very significant contribution to the dynamic CBFV response to changes in MAP and plays a major role in explaining the deterioration of dynamic CA induced by hypercapnia. Further studies are needed to assess the relevance of CrCP contribution in physiological and clinical studies.

COHmax: an algorithm to maximise coherence in estimates of dynamic cerebral autoregulation.

OBJECTIVE: The reliability of dynamic cerebral autoregulation (dCA) parameters, obtained with transfer function analysis (TFA) of spontaneous fluctuations in arterial blood pressure (BP), require statistically significant values of the coherence function. A new algorithm (COHmax) is proposed to increase values of coherence by means of the automated, selective removal of sub-segments of data. APPROACH: Healthy subjects were studied at baseline (normocapnia) and during 5% breathing of CO2 (hypercapnia). BP (Finapres), cerebral blood flow velocity (CBFV, transcranial Doppler), end-tidal CO2 (EtCO2, capnography) and heart rate (ECG) were recorded continuously during 5 min in each condition. TFA was performed with sub-segments of data of duration (SEGD) 100 s, 50 s or 25 s and the autoregulation index (ARI) was obtained from the CBFV response to a step change in BP. The area-under-the curve (AUC) was obtained from the receiver-operating characteristic (ROC) curve for the detection of changes in dCA resulting from hypercapnia. MAIN RESULTS: In 120 healthy subjects (69 male, age range 20-77 years), CO2 breathing was effective in changing mean EtCO2 and CBFV (p < 0.001). For SEGD = 100 s, ARI changed from 5.8 ± 1.4 (normocapnia) to 4.0 ± 1.7 (hypercapnia, p < 0.0001), with similar differences for SEGD = 50 s or 25 s. Depending on the value of SEGD, in normocapnia, 15.8% to 18.3% of ARI estimates were rejected due to poor coherence, with corresponding rates of 8.3% to 13.3% in hypercapnia. With increasing coherence, 36.4% to 63.2% of these could be recovered in normocapnia (p < 0.001) and 50.0% to 83.0% in hypercapnia (p < 0.005). For SEGD = 100 s, ROC AUC was not influenced by the algorithm, but it was superior to corresponding values for SEGD = 50 s or 25 s. SIGNIFICANCE: COHmax has the potential to improve the yield of TFA estimates of dCA parameters, without introducing a bias or deterioration of their ability to detect impairment of autoregulation. Further studies are needed to assess the behaviour of the algorithm in patients with different cerebrovascular conditions.

Chasing the evidence: the influence of data segmentation on estimates of dynamic cerebral autoregulation.

OBJECTIVE: Transfer function analysis (TFA) of dynamic cerebral autoregulation (dCA) requires smoothing of spectral estimates using segmentation of the data (SD). Systematic studies are required to elucidate the potential influence of SD on dCA parameters. APPROACH: Healthy subjects (HS, n = 237) and acute ischaemic stroke patients (AIS, n = 98) were included. Cerebral blood flow velocity (CBFV, transcranial Doppler ultrasound) was recorded supine at rest with continuous arterial blood pressure (BP, Finometer) for a minimum of 5 min. TFA was performed with durations SD = 100, 50 or 25 s and 50% superposition to derive estimates of coherence, gain and phase for the BP-CBFV relationship. The autoregulation index (ARI) was estimated from the CBFV step response. Intrasubject reproducibility was expressed by the intraclass correlation coefficient (ICC). MAIN RESULTS: In HS, the ARI, coherence, gain, and phase (low frequency) were influenced by SD, but in AIS, phase (very low frequency) and ARI were not affected. ICC was excellent (>0.75) for all parameters, for both HS and AIS. For SD = 100 s, ARI was different between HS and AIS (mean ± sdev: 5.70 ± 1.61 vs 5.1 ± 2.0; p < 0.01) and the significance of this difference was maintained for SD = 50 s and 25 s. Using SD = 100 s as reference, the rate of misclassification, based on a threshold of ARI ⩽ 4, was 6.3% for SD = 50 s and 8.1% for SD = 25 s in HS, with corresponding values of 11.7% and 8.2% in AIS patients, respectively. SIGNIFICANCE: Further studies are warranted with SD values lower than the recommended standard of SD = 100 s, to explore possibilities of improving the reproducibility, sensitivity and prognostic value of TFA parameters used as metrics of dCA.

Evaluation of the cost-effectiveness of rifaximin-α for the management of patients with hepatic encephalopathy in the United Kingdom.

OBJECTIVE: Rifaximin-α 550 mg twice daily plus lactulose has demonstrated efficacy in reducing recurrence of episodes of overt hepatic encephalopathy (OHE) and the risk of hepatic encephalopathy (HE)-related hospitalizations compared with lactulose alone. This analysis estimated the cost effectiveness of rifaximin-α 550 mg twice daily plus lactulose versus lactulose alone in United Kingdom (UK) cirrhotic patients with OHE. METHOD: A Markov model was built to estimate the incremental cost-effectiveness ratio (ICER). The perspective was that of the UK National Health Service (NHS). Clinical data was sourced from a randomized controlled trial (RCT) and an open-label maintenance study in cirrhotic patients in remission from recurrent episodes of OHE. Health-related utility was estimated indirectly from disease-specific quality of life RCT data. Resource use data describing the impact of rifaximin-α on hospital admissions and length of stay for cirrhotic patients with OHE was from four single-center UK audits. Costs (2012) were derived from published sources; costs and benefits were discounted at 3.5%. The base-case time horizon was 5 years. RESULTS: The average cost per patient was £22,971 in the rifaximin-α plus lactulose arm and £23,545 in the lactulose arm, a saving of £573. The corresponding values for benefit were 2.35 quality adjusted life years (QALYs) and 1.83 QALYs per person, a difference of 0.52 QALYs. This translated into a dominant base-case ICER. Key parameters that impacted the ICER included number of hospital admissions and length of stay. CONCLUSION: Rifaximin-α 550 mg twice daily in patients with recurrent episodes of OHE was estimated to generate cost savings and improved clinical outcomes compared to standard care over 5 years.

Effect of the GSTM1 gene deletion on glycemic variability, sympatho-vagal balance and arterial stiffness in patients with metabolic syndrome, but without diabetes.

AIMS: An increased rate of cerebrovascular complications in patients with metabolic syndrome (MetS) has been reported. Previous studies demonstrated an association between glycemic variability (GV) and cerebrovascular reactivity (CRV) in MetS, thus suggesting a putative role of GV on cerebrovascular events. Although the pathophysiological mechanism linking GV to damage is still to be elucidated, evidence suggests oxidative stress plays a crucial role. Since functional variants in glutathione S-transferases (GST) genes modulate the cellular detoxification processes, the aim of this study was to elucidate the involvement of GSTs in MetS and investigating the correlation with GV, arterial stiffness, and sympatho-vagal (SV) balance. METHODS: A hundred metabolic syndrome patients without diabetes underwent GST gene polymorphism analysis and a sub-sample 36 patients were randomly selected to investigate the correlation between GST gene polymorphisms and GV, and sympatho-vagal (SV) balance and arterial stiffness. RESULTS: GSTM1 showed a significant association with several GV, arterial stiffness, and SV balance indexes. In particular, the GSTM1 deletion positively correlates with lower values of these indexes when compared to the presence of the gene. CONCLUSIONS: Therefore, we suggested a global influence of GSTM1 deletion on the GV, arterial stiffness, and SV balance pathways in MetS patients, probably also interacting with AMP-activated protein kinase (AMPK) regulation. Our novel findings indicate GSTM1 could be a risk locus in MetS development and shed light novel scenarios on the role of glucose fluctuations in neurological impairments.

The impact of rifaximin-α on the hospital resource use associated with the management of patients with hepatic encephalopathy: a retrospective observational study (IMPRESS).

OBJECTIVE: To compare all-cause and liver-related hospital resource use in the 6 and 12 months pre-rifaximin-α and post-rifaximin-α initiation in UK patients with hepatic encephalopathy (HE). DESIGN: A UK multicentre, retrospective, observational study. Patients' medical records were reviewed for demographics, clinical outcomes and adverse events (AEs) to rifaximin-α. Details of hospital admissions/attendances in the 6 and 12 months pre-rifaximin-α and post-rifaximin-α initiation were extracted from hospital electronic databases. SETTING: 13 National Health Service centres. PATIENTS: 207 patients with HE who initiated rifaximin-α between July 2008 and May 2014. Hospital resource use data were available for 145/207 patients. MAIN OUTCOME MEASURE: Change in mean number of liver-related hospital bed days/patient (total and critical care) between the 6 months pre-rifaximin-α and post-rifaximin-α initiation. RESULTS: Comparing the 6 months pre-rifaximin-α and post-rifaximin-α initiation in alive patients at the end of the observation period (N=114): there were significant reductions in the mean number of hospitalisations/patient (liver-related 1.3 to 0.5, p<0.001; all-cause 1.9 to 0.9, p<0.001), hospital bed days/patient (liver-related 17.8 to 6.8, p<0.001; all-cause 25.4 to 10.6, p<0.001), 30-day hospital readmissions/patient (liver-related 0.5 to 0.2, p=0.039; all-cause 0.8 to 0.4, p=0.024) and emergency department (ED) attendances/patient (all-cause, 1.0 to 0.5, p<0.001). The mean critical care bed days/patient reduced significantly for all-cause admissions (1.3 to 0.3, p=0.049); non-significant reduction for liver-related admissions. 4% of patients (9/207) developed AEs. CONCLUSIONS: In UK clinical practice, treatment with rifaximin-α for HE is well-tolerated and associated with significant reductions in hospitalisations, bed days (including critical care), ED attendances and 30-day readmissions.

The Role of White Matter Damage in the Risk of Periprocedural Diffusion-Weighted Lesions after Carotid Artery Stenting.

BACKGROUND: White matter hyperintensities (WMH) are a common finding in aged individuals affected by carotid artery disease and are a risk factor for first-ever and recurrent stroke. We investigated if white matter damage increases the risk of brain microembolism during carotid artery stenting (CAS), as evaluated by the appearance of new areas of restricted diffusion on diffusion-weighted images (DWI). METHODS: We evaluated 47 patients with severe internal carotid artery (ICA) stenosis undergoing CAS, comparing preprocedural clinical, ultrasound and radiological characteristics. WMH volume was computed on FLAIR images before CAS. After CAS, the DWI scan was looked over for areas of restricted diffusion (DWI lesions). A first univariate analysis was adopted to compare groups according to the occurrence of DWI lesions. Then, the variable DWI lesion was modelled by means of a logistic regression model. RESULTS: Seventeen patients developed at least 1 DWI lesion after CAS. Compared with non-DWI, DWI patients were more commonly treated in the left ICA (p = 0.007) and had a more severe WMH damage (p = 0.027). Indeed, the risk of a DWI lesion was higher in left versus right stenosis (OR = 9.0, 95% CI 1.9-42.7, p = 0.005) and increased for each log-unit of WMH lesion load (OR = 7.05, 95% CI 1.07-46.49, p = 0.042). A WMH lesion load of at least 5.25 cm3 had a 50% probability of occurrence of a new DWI lesion. CONCLUSIONS: Treated side and preexisting white matter damage are risk conditions for brain microembolism during CAS. This should be taken into account to optimize severe carotid artery disease management.

Vegetarian diet and excessive tea consumption: a dangerous association?

Rare metabolic diseases may sometimes arise acutely and endanger human life if not immediately recognized and treated. Marchiafava Bignami disease is an uncommon neurologic disorder described in alcohol abusers and characterized by an acute severe damage of brain white matter. Even more rarely, it has been reported in non-alcohol addicted patients, but never in vegetarian people. This is a case report of a young vegetarian woman, accustomed to drink high amounts of tea, who, three weeks after her first natural childbirth, developed serious motor and cognitive disturbances. A timely brain magnetic resonance (MR) allowed us to identify Marchiafava Bignami disease and she healed few hours after the administration of parenteral steroids and vitamins. We advise to suspect Marchiafava Bignami Disease in all patients presenting with non-obvious acute generalized motor and cognitive disturbances, also if non alcoholics, and to collect the nutritional habits in all patients with suspected symptoms. In these cases a timely brain MRI is warranted, since brain imaging is typical and patients may recover after a prompt treatment.

Effects of continuous renal replacement therapy on linezolid pharmacokinetic/pharmacodynamics: a systematic review.

BACKGROUND: Major alterations in linezolid pharmacokinetic/pharmacodynamic (PK/PD) parameters might be expected in critically ill septic patients with acute kidney injury (AKI) who are undergoing continuous renal replacement therapy (CRRT). The present review is aimed at describing extracorporeal removal of linezolid and the main PK-PD parameter changes observed in critically ill septic patients with AKI, who are on CRRT. METHOD: Citations published on PubMed up to January 2016 were systematically reviewed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. All authors assessed the methodological quality of the studies and consensus was used to ensure studies met inclusion criteria. In-vivo studies in adult patients with AKI treated with linezolid and on CRRT were considered eligible for the analysis only if operational settings of the CRRT machine, membrane type, linezolid blood concentrations and main PK-PD parameters were all clearly reported. RESULTS: Among 68 potentially relevant articles, only 9 were considered eligible for the analysis. Across these, 53 treatments were identified among the 49 patients included (46 treated with high-flux and 3 with high cut-off membranes). Continuous veno-venous hemofiltration (CVVH) was the most frequent treatment performed amongst the studies. The extracorporeal clearance values of linezolid across the different modalities were 1.2-2.3 L/h for CVVH, 0.9-2.2 L/h for hemodiafiltration and 2.3 L/h for hemodialysis, and large variability in PK/PD parameters was reported. The optimal area under the curve/minimum inhibitory concentration (AUC/MIC) ratio was reached for pathogens with an MIC of 4 mg/L in one study only. CONCLUSIONS: Wide variability in linezolid PK/PD parameters has been observed across critically ill septic patients with AKI treated with CRRT. Particular attention should be paid to linezolid therapy in order to avoid antibiotic failure in these patients. Strategies to improve the effectiveness of this antimicrobial therapy (such as routine use of target drug monitoring, increased posology or extended infusion) should be carefully evaluated, both in clinical and research settings.

Regional MRI Diffusion, White-Matter Hyperintensities, and Cognitive Function in Alzheimer's Disease and Vascular Dementia.

BACKGROUND AND PURPOSE: An increase in brain water diffusivity as measured using magnetic resonance imaging (MRI) has been recently reported in normal-appearing white matter (NAWM) in patients affected by cognitive impairment. However, it remains to be clarified if this reflects an overt neuronal tissue disruption that leads to degenerative or microvascular lesions. This question was addressed by comparing the regional MRI apparent diffusion coefficients (ADCs) of NAWM in patients affected by Alzheimer's disease (AD) or vascular dementia (VaD). The relationships of ADCs with the white-matter hyperintensity (WMH) burden, carotid atherosclerosis, and cognitive performance were also investigated. METHODS: Forty-nine AD and 31 VaD patients underwent brain MRI to assess the WMH volume and regional NAWM ADCs, neuropsychological evaluations, and carotid ultrasound to assess the plaque severity and intima-media thickness (IMT). RESULTS: Regional ADCs in NAWM did not differ between VaD and AD patients, while the WMH volume was greater in VaD than in AD patients. The ADC in the anterior corpus callosum was related to the WMH volume, while a greater carotid IMT was positively correlated with the temporal ADC and WMH volume. The memory performance was worse in patients with higher temporal ADCs. Constructional praxis scores were related to ADCs in the frontal, and occipital lobes, in the anterior and posterior corpus callosum as well as to the WMH volume. Abstract reasoning was related to frontal, parietal, and temporal ADCs. CONCLUSIONS: Our data show that higher regional ADCs in NAWM are associated with microcirculatory impairment, as depicted by the WMH volume. Moreover, regional ADCs in NAWM are differently associated with the neuropsychological performances in memory, constructional praxia, and abstract reasoning domains.

Cortical ischemic lesion burden measured by DIR is related to carotid artery disease severity.

BACKGROUND: Over time, exposure to cerebrovascular risk factors and carotid artery disease may cause multiple asymptomatic brain cortical and subcortical microinfarcts, which are commonly found at brain autopsy. So far, lack of convenient neuroimaging tools limited the investigation of grey matter ischemic damage in vivo. We applied the Double Inversion Recovery (DIR) sequence to explore the impact of carotid artery disease on intracortical ischemic lesion load in vivo, taking into account the impact of demographic characteristics and vascular risk factors. METHODS: DIR was acquired in 62 patients with common cerebrovascular risk factors stratified in three groups according to carotid artery disease severity. Intracortical lesions scored on DIR (DIRlns) were classified by vascular territory, lobe and hemisphere. White matter hyperintensities (WMHs) volume was also quantified on Fluid Attenuated Inversion Recovery sequence (FLAIR). RESULTS: Among demographic characteristics and cerebrovascular risk variables explored, General Linear Model indicated that age and carotid artery disease were significantly associated to DIRlns. After correcting for age, DIRlns load was found to be significantly dependent on carotid artery stenosis severity (F(2, 58) = 5.56, p = 0.006). A linear positive correlation between DIRlns and WMHs was found after correcting for age (p = 0.003). CONCLUSIONS: Carotid disease severity is associated with DIRlns accrual. Microembolism and impaired cerebral hemodynamics may act as physiopathological mechanisms underlying cortical ischemic damage. The role of other factors, such as small vessel disease and the possible interaction with carotid disease, remains to be further explored.

Role of hemodialysis with high cut-off membranes in a patient with a non-recognized leishmaniasis.

BACKGROUND: We report here a case of a woman affected by fever, weight loss, splenomegaly, and leucopenia associated with trombocytopenia, transferred to the intensive care unit with acute kidney injury and septic shock. METHODS: Patient was treated with high cut-off continuous veno-venous hemodialysis (HCO-CVVHD). RESULTS: During treatment, the patient experienced a stable improvement in the hemodynamic, pulmonary function and tissue perfusion parameters. After 48 h of treatment, significant reductions in SOFA score (from 12, before starting the procedure, to 6) and in serum inflammatory mediators (as IL-6, from 599-568 pg/ml) were observed. Leishmania infection was identified as responsible of the septic condition only 48 h after removing hemodialysis. Antiprotozoal therapy was begun and the patient discharged. CONCLUSIONS: By supporting the renal function and reducing systemic inflammation, HCO-CVVHD could be a useful bridge therapy. This procedure allowed the medical team to gain sufficient time to diagnose the type of infection and begin an etiological therapy.

Influence of CO2 on neurovascular coupling: interaction with dynamic cerebral autoregulation and cerebrovascular reactivity.

Abstract PaCO2 affects cerebral blood flow (CBF) and its regulatory mechanisms, but the interaction between neurovascular coupling (NVC), cerebral autoregulation (CA), and cerebrovascular reactivity to CO2 (CVR), in response to hypercapnia, is not known. Recordings of cerebral blood flow velocity (CBFv), blood pressure (BP), heart rate, and end-tidal CO2 (EtCO2) were performed in 18 subjects during normocapnia and 5% CO2 inhalation while performing a passive motor paradigm. Together with BP and EtCO2, a gate signal to represent the effect of stimulation was used as input to a multivariate autoregressive-moving average model to calculate their separate effects on CBFv. Hypercapnia led to a depression of dynamic CA at rest and during stimulation in both hemispheres (P < 0.02) as well as impairment of the NVC response, particularly in the ipsilateral hemisphere (P < 0.01). Neither hypercapnia nor the passive motor stimulation influenced CVR. Dynamic CA was not influenced by the motor paradigm during normocapnia. The CBFv step responses to each individual input (BP, EtCO2, stimulation) allowed identification of the influences of hypercapnia and neuromotor stimulation on CA, CVR, and NVC, which have not been previously described, and also confirmed the depressing effects of hypercapnia on CA and NVC. The stability of CVR during these maneuvers and the lack of influence of stimulation on dynamic CA are novel findings which deserve further investigation. Dynamic multivariate modeling can identify the complex interplay between different CBF regulatory mechanisms and should be recommended for studies involving similar interactions, such as the effects of exercise or posture on cerebral hemodynamics.

1-Hz repetitive transcranial magnetic stimulation increases cerebral vasomotor reactivity: a possible autonomic nervous system modulation.

BACKGROUND: Neuromodulation techniques, i.e. repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), can modify cerebral hemodynamics. High frequency rTMS appeared to decrease cerebral vasomotor reactivity (VMR), while there is still poor evidence about the effect of low frequency (LF) rTMS on cerebral blood flow (CBF) and VMR. HYPOTHESIS: The present study aimed to test if LF rTMS decreases CBF and increases cerebral VMR. Monolateral or bilateral hemispheric involvement and duration of the effect were considered. A possible role of autonomic nervous system in CBF and VMR modulation was also investigated. METHODS: Twenty-four right-handed healthy subjects underwent randomly real (12) or sham (12) 20-min 1-Hz rTMS on left primary motor cortex. Mean flow velocity and VMR of middle cerebral arteries were evaluated by means of transcranial Doppler before (T0), after 10 min (T1) and after 2 (T2), 5 (T3) and 24 h (T4) from rTMS. Heart rate variability (HRV) was studied within the same timing interval, assessing low frequency/high frequency (LF/HF) ratio as index of autonomic balance. RESULTS: After real rTMS compared with sham stimulation, MFV decreased bilaterally at T1 (F = 3.240, P = .030) while VMR increased bilaterally (F = 5.116, P = .002) for at least 5 h (T3). LF/HF ratio decreased early after real rTMS (F = 2.881, P = .040). CONCLUSION: 1-Hz rTMS may induce a bilateral long-lasting increase of VMR, while its effect on MFV is short-lasting. Moreover, HRV changes induced by rTMS suggest a possible autonomic nervous system modulation.