Publications by authors named "Paola Palazzo"

55 Publications

Predictors of Early Stroke or Death in Patients Undergoing Transcatheter Aortic Valve Implantation.

J Stroke Cerebrovasc Dis 2021 Aug 12;30(8):105912. Epub 2021 Jun 12.

Department of Neurology, CHU La Milétrie, Poitiers, France and University of Poitiers, France.

Background/objective: While postoperative stroke is a known complication of Transcatheter Aortic Valve Implantation (TAVI), predictors of early stroke occurrence have not been specifically reviewed. The objective of this study was to estimate the predictors and incidence of stroke during the first 30 days post-TAVI.

Methods: A cohort of 506 consecutive patients having undergone TAVI between January 2017 and June 2019 was extracted from a prospective database. Preoperative, intraoperative and postoperative characteristics were analyzed by univariate analysis followed by logistic regression to find predictors of the occurrence of stroke or death within the first 30 days after the procedure.

Results: Incidence of stroke within 30 days post-TAVI was 4.9%, [CI 95% 3.3-7.2], i.e., 25 strokes. Four out of the 25 patients (16%) with a stroke died within 30 days post-TAVI. After logistic regression analysis, the predictors of early stroke related to TAVI were: CHA2Ds2VASc score ≥ 5 (odds ratio [OR] 2.62; 95% CI: 1.06-6.49; p = .037), supra-aortic access vs. femoral access (OR: 9.00, 95%CI: 2.95-27.44; p = .001) and introduction post-TAVI of a single vs. two or three antithrombotic agents (OR: 5.13; CI 95%: 1.99 to 13.19; p = .001). Over the 30-day period, bleeding occurred in 28 patients (5.5%), in 25 of whom, it was associated with femoral or iliac artery access injury. Anti-thrombotic regimen was not associated with bleeding; two patients out of 48 (4.1%) bled with a single anti-thrombotic regimen vs. 26 patients out of 458 (5.6%) with a dual or triple anti-thrombotic regimen (p = 0.94). The overall 30-day mortality rate was 3.9%, [95% CI 2.5-6.0]. Patients with a single post-TAVI antithrombotic agent (OR: 44.07 [CI 95% 13.45-144.39]; p < .0001) and patients with previous coronary artery bypass surgery or coronary artery stenting (OR: 6.16, [CI 95% 1.99-21.29]; p = .002) were at significantly higher risk of death within the 30-day period.

Conclusion: In this large-scale single-center retrospective study, a single post-TAVI antithrombotic regimen independently predicted occurrence of early stroke or death. Dual or triple antithrombotic regimen was not associated with a higher risk of bleeding and should be considered as an option in patients undergoing TAVI.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105912DOI Listing
August 2021

Chlorhexidine plus alcohol versus povidone iodine plus alcohol, combined or not with innovative devices, for prevention of short-term peripheral venous catheter infection and failure (CLEAN 3 study): an investigator-initiated, open-label, single centre, randomised-controlled, two-by-two factorial trial.

Lancet Infect Dis 2021 07 1;21(7):1038-1048. Epub 2021 Feb 1.

Service des Urgences et SAMU 86 Centre 15, CHU de Poitiers, France; Université de Poitiers, UFR de Médecine-Pharmacie, Poitiers, France; INSERM U1070, Pharmacologie des Agents Anti-Infectieux, Poitiers, France. Electronic address:

Background: Two billion peripheral venous catheters are sold globally each year, but the optimal skin disinfection and types of devices are not well established. We aimed to show the superiority of disinfection with 2% chlorhexidine plus alcohol over 5% povidone iodine plus alcohol in preventing infectious complications, and of closed integrated catheters, positive displacement needleless-connectors, disinfecting caps, and single-use prefilled flush syringes used in combination (innovation group) over open catheters and three-way stopcocks for treatment administration (standard group) in preventing catheter failure.

Methods: We did an open-label, randomised-controlled trial with a two-by-two factorial design, for which we enrolled adults (age ≥18 years) visiting the emergency department at the Poitiers University Hospital, France, and requiring one peripheral venous catheter before admission to the medical wards. Before catheter insertion, patients were randomly assigned (1:1:1:1) using a secure web-based random-number generator to one of four treatment groups based on skin preparation and type of devices (innovative devices or standard devices; 2% chlorhexidine plus alcohol or 5% povidone iodine plus alcohol). Primary outcomes were the incidence of infectious complications (local infection, catheter colonisation, or bloodstream infections) and time between catheter insertion and catheter failure (occlusion, dislodgment, infiltration, phlebitis, or infection). This study is registered with ClinicalTrials.gov, NCT03757143.

Findings: 1000 patients were recruited between Jan 7, and Sept 6, 2019, of whom 500 were assigned to the chlorhexidine plus alcohol group and 500 to the povidone iodine plus alcohol group (250 with innovative solutions and 250 with standard devices in each antiseptic group). No significant interaction was found between the two study interventions. Local infections occurred less frequently with chlorhexidine plus alcohol than with povidone iodine plus alcohol (0 [0%] of 496 patients vs six [1%] of 493 patients) and the same was observed for catheter colonisation (4/431 [1%] vs 70/415 [17%] catheters among the catheters cultured; adjusted subdistribution hazard ratio 0·08 [95% CI 0·02-0·18]). Median time between catheter insertion and catheter failure was longer in the innovation group compared with the standard group (50·4 [IQR 29·6-69·4] h vs 30·0 [16·6-52·6] h; p=0·0017). Minor skin reactions occurred in nine (2%) patients in the chlorhexidine plus alcohol group and seven (1%) patients in the povidone iodine plus alcohol group.

Interpretation: For skin antisepsis, chlorhexidine plus alcohol provides greater protection of peripheral venous catheter-related infectious complications than does povidone iodine plus alcohol. Use of innovative devices extends the catheter complication-free dwell time.

Funding: Becton Dickinson.
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http://dx.doi.org/10.1016/S1473-3099(20)30738-6DOI Listing
July 2021

SiPP (Stroke in Pregnancy and Postpartum): A prospective, observational, international, multicentre study on pathophysiological mechanisms, clinical profile, management and outcome of cerebrovascular diseases in pregnant and postpartum women.

Eur Stroke J 2020 Jun 6;5(2):193-203. Epub 2019 Dec 6.

Department of Neurosciences (Neurology), Hospital de Santa Maria, University of Lisbon, Lisbon, Portugal.

Rationale: Cerebrovascular diseases associated with pregnancy and postpartum period are uncommon; however, they can have an important impact on health of both women and foetus or newborn.

Aims: To evaluate the frequency, characteristics and management of cerebrovascular events in pregnant/postpartum women, to clarify pathophysiological mechanisms underlying the occurrence of these events including biomolecular aspects, and to assess the short- and long-term cerebrovascular and global cardiovascular outcome of these patients, their predictors and infant outcome.

Methods And Design: This is an observational, prospective, multicentre, international case-control study. The study will include patients with cerebrovascular events during pregnancy and/or within six months after delivery. For each included case, two controls will be prospectively recruited: one pregnant or puerperal subject without any history of cerebrovascular event and one non-pregnant or non-puerperal subject with a recent cerebrovascular event. All controls will be matched by age, ethnicity and type of cerebrovascular event with their assigned cases. The pregnant controls will be matched also by pregnancy weeks/trimester. Follow-up will last 24 months for the mother and 12 months for the infant.

Summary: To better understand causes and outcomes of uncommon conditions like pregnancy/postpartum-related cerebrovascular events, the development of multisite, multidisciplinary registry-based studies, such as the Stroke in Pregnancy and Postpartum study, is needed in order to collect an adequate number of patients, draw reliable conclusions and give definite recommendations on their management.
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http://dx.doi.org/10.1177/2396987319893512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313370PMC
June 2020

Transcranial Doppler to detect right-to-left shunt in cryptogenic acute ischemic stroke.

Brain Behav 2019 01 1;9(1):e01091. Epub 2018 Dec 1.

Department of Neurology, Poitiers University Hospital, Poitiers Cedex, France.

Objectives: We aimed to confirm the sensitivity and specificity of contrast transcranial Doppler (cTCD) in the detection of right-to-left shunt (RLS) compared to the current reference standard (i.e., transesophageal echocardiography-TEE) in patients aged <55 years with a cryptogenic acute ischemic stroke (AIS) or high-risk (ABCD score ≥4) transient ischemic attack (TIA), and to calculate the real life delay in detecting RLS by cTCD versus TEE in a tertiary care academic stroke center.

Methods: Consecutive 16- to 54-year-old patients with AIS or high-risk TIA underwent complete diagnostic workup which included, in case of undetermined etiology, cTCD and TEE. Sensitivity and specificity of cTCD, RLS characteristics, and median delay between the two tests were calculated.

Results: Of the 98 included patients, 52 (53%) had a cryptogenic cerebrovascular ischemic event, which displayed a 56% prevalence of RLS related to a patent foramen ovale (PFO) mainly with a high-grade shunt. When comparing TCD with "bubble test" to TEE, sensitivity and specificity were both 100%. Median delays from symptom onset to examination were 2 (min-max 1-10) and 21 (min-max 1-60) days, respectively, for cTCD and TEE. No adverse event occurred during or after cTDC examination.

Conclusions: Transcranial Doppler with "bubble test" appears as the best screening test for the detection of RLS in young and middle-aged adults with cryptogenic acute cerebral ischemic events to select patients potentially suitable for closure procedure after TEE confirmation.
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http://dx.doi.org/10.1002/brb3.1091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346730PMC
January 2019

Back to Basics: Adherence With Guidelines for Glucose and Temperature Control in an American Comprehensive Stroke Center Sample.

J Neurosci Nurs 2018 Jun;50(3):131-137

Questions or comments about this article may be directed to Anne W. Alexandrov, PhD RN AGACNP-BC CCRN NVRN-BC ANVP-BC FAAN, at She is Professor of Nursing and Professor of Neurology, Department of Acute and Critical Care, College of Nursing, and Department of Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN; and NET SMART, Health Outcomes Institute, Fountain Hills, AZ. Paola Palazzo, MD, is Stroke Neurologist, Department of Neurology, Poitiers University Hospital, Poitiers, France; and San Giovanni Calibita Fatebenefratelli Hospital, Rome, Italy. Sharon Biby, MSN RN AGPCNP-BC ANVP-BC, NET SMART, is Stroke Team Nurse Practitioner, Health Outcomes Institute, Fountain Hills, AZ; and The Moses Cone Memorial Hospital, Cone Health, Greensboro, NC. Abbigayle Doerr, DNP RN FNP-BC ANVP-BC, NET SMART, is Manager, Interventional Labs, Health Outcomes Institute, Fountain Hills, AZ; and Northwestern Medicine, Central DuPage Hospital, Winfield, IL. Wendy Dusenbury, DNP RN AGACNP-BC FNP-BC ANVP-BC, is Stroke Team Nurse Practitioners, Department of Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN; NET SMART, Health Outcomes Institute, Fountain Hills, AZ; and Assistant Professor, College of Nursing, Wichita State University, Wichita, KS. Rhonda Young, MSN RN FNP-BC ANVP-BC, is Nurse Practitioner, The Little Clinic, Wichita, KS. Anne Lindstrom, is Stroke Program Director, MSN RN FNP-BC, Northwestern Medicine, Central DuPage Hospital, Winfield, IL. Mary Grove, MSN RN ACNP-BC, is PhD Candidate, Department of Acute and Critical Care, College of Nursing, University of Tennessee Health Science Center, Memphis, TN; and Institute for Evidence Based Care, Hackensack Meridian Health, Neptune, NJ. Georgios Tsivgoulis, MD PhD, is Professor, Department of Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN; and Second Department of Neurology, Attikon University Hospital, Chaidari, and School of Medicine, University of Athens, Athens, Greece. Sandy Middleton, PhD RN, is Professor of Nursing, Nursing Research Institute, Australian Catholic University, and St Vincent's Health Australia, Sydney, Australia. Andrei V. Alexandrov, MD, is Professor and Chairman, Department of Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN.

Background: Variance from guideline-directed care for glucose and temperature control remains unknown in the United States at a time when priorities have shifted to ensure rapid diagnosis and treatment of acute stroke patients. However, protocol-driven nursing surveillance for control of hyperglycemia and hyperthermia has been shown to improve patient outcomes.

Methods: We conducted an observational pilot study to assess compliance with American guidelines for glucose and temperature control and association with discharge outcomes in consecutive acute stroke patients admitted to 5 US comprehensive stroke centers. Data for the first 5 days of stroke admission were collected from electronic medical records and entered and analyzed in SPSS using descriptive statistics, Mann-Whitney U test, Student t tests, and logistic regression.

Results: A total of 1669 consecutive glucose and 3782 consecutive temperature measurements were taken from a sample of 235 acute stroke patients; the sample was 87% ischemic and 13% intracerebral hemorrhage. Poor glucose control was found in 33% of patients, and the most frequent control method ordered (35%) was regular insulin sliding scale without basal dosing. Poor temperature control was noted in 10%, and 39% did not have temperature recorded in the emergency department. Lower admission National Institutes of Health Stroke Scale score and well-controlled glucose were independent predictors of favorable outcome (discharge modified Rankin Scale score, 0-2) in reperfusion patients.

Conclusion: Glucose and temperature control may be overlooked in this era of rapid stroke diagnosis and treatment. Acute stroke nurses are well positioned to assume leadership of glucose and temperature monitoring and treatment.
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http://dx.doi.org/10.1097/JNN.0000000000000358DOI Listing
June 2018

Should We Screen for Janus Kinase 2 V617F Mutation in Cerebral Venous Thrombosis?

Cerebrovasc Dis 2017 14;44(3-4):97-104. Epub 2017 Jun 14.

Department of Neurology, S. Giovanni Calibita-Fatebenefratelli Hospital, Rome, Italy.

Background: The presence of Janus Kinase 2 (JAK2) V617F mutation represents a major diagnostic criterion for detecting myeloproliferative neoplasms (MPN) and even in the absence of overt MPN, JAK2 V617F mutation is associated with splanchnic vein thrombosis. However, the actual prevalence and diagnostic value of the JAK2 V617F mutation in patients with cerebral venous thrombosis (CVT) are not known. The aims of this study were to assess the prevalence of JAK2 V617F mutation in a large group of consecutive CVT patients, to detect clinical, biological, and radiological features associated with the mutation, and to determine the long-term venous thrombosis recurrence rate in CVT patients with JAK2 mutation but without overt MPN in order to recommend the best preventive treatment.

Methods: This was a prospective study conducted on consecutive patients with a first-ever radiologically confirmed CVT. JAK2 V617F mutation analysis was assessed in all the study subjects. JAK2 V617F-positive patients were followed up to detect new venous thrombotic events.

Results: Of the 125 included subjects, 7 were found to have JAK2 V617F mutation (5.6%; 95% CI 2.3-11.2). Older age (p = 0.039) and higher platelet count (p = 0.004) were independently associated with JAK2 V617F positivity in patients without overt MPN. During a mean follow-up period of 59 (SD 46) months, 2 JAK2 V617F-positive patients presented with 4 new venous thromboembolic events.

Conclusions: Screening for the JAK2 V617F mutation in CVT patients seems to be useful even in the absence of overt MPN and/or in the presence of other risk factors for CVT because of its relatively high prevalence and the risk of thrombosis recurrence.
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http://dx.doi.org/10.1159/000471891DOI Listing
June 2018

Venous Thrombotic Recurrence After Cerebral Venous Thrombosis: A Long-Term Follow-Up Study.

Stroke 2017 Feb 15;48(2):321-326. Epub 2016 Dec 15.

From the Department of Neurology, Poitiers University Hospital and University of Poitiers, France (P.P., P.A., J.C., M.L., A.B., P.C., J.-P.N.); Department of Neurology, S. Giovanni Calibita-Fatebenefratelli Hospital, Rome, Italy (P.P.); and Clinical Investigation Center INSERM CIC-P 802, Poitiers University Hospital, France (P.I.).

Background And Purpose: After cerebral venous thrombosis (CVT), the risk of venous thrombotic events was estimated at 2% to 3% for a new CVT and 3% to 8% for extracranial events. However, because of the paucity of prospective studies, the clinical course of CVT is still largely unknown. We aimed to prospectively evaluate the rate of thrombosis recurrence in a cohort of CVT patients with a long-term follow-up and to detect predisposing factors for recurrence.

Methods: Consecutive CVT patients with complete clinical, radiological, biological, and genetic data were systematically followed up. New venous thrombotic events were detected after hospital readmission and imaging confirmation.

Results: One-hundred eighty-seven patients (mean age 45±18 years, 67% women) with angiographically confirmed CVT were included. Cause was found in 73% of patients. Coagulation abnormality and JAK2 gene mutation were detected in 20% and 9%, respectively. Median follow-up length was 73 months (range 1-247 months). Mean duration of the oral anticoagulant treatment was 14 months. Mortality rate was 2.5% per year, with 2% in-hospital mortality. During follow-up, CVT reoccurred in 6 patients, whereas 19 subjects had a symptomatic extracranial venous thrombotic event, with cumulative venous thrombotic recurrence rates of 3% at 1 year, 8% at 2 years, 12% at 5 years, and 18% at 10 years. A previous venous thrombotic event (hazard ratio, 2.8; P=0.018), presence of cancer or malignant hemopathies (hazard ratio, 3.2; P=0.039), and unknown CVT causes (hazard ratio, 2.81; P=0.024) were independently associated with recurrence.

Conclusions: In our cohort of CVT patients followed on average for >6 years, subjects with a previous venous thrombotic event, cancer/malignant hemopathies, and unknown CVT causes were found to be at higher risk of recurrence.
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http://dx.doi.org/10.1161/STROKEAHA.116.015294DOI Listing
February 2017

Long-term outcome of basilar stenosis in Erdheim-Chester disease: A case report.

Medicine (Baltimore) 2016 Sep;95(36):e4813

Department of Neurology, CHU of Poitiers, University of Poitiers, Poitiers Department of Internal Medicine and French reference Center for Rare Auto-immune and Systemic Diseases, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital Université Pierre et Marie Curie, UPMC University Paris 6, Paris Department of Pathology, CHU of Poitiers, University of Poitiers, Poitiers, France.

Background: Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis. This inflammatory myeloid neoplasm is frequently complicated by neurological symptoms, but stroke is an exceptional manifestation of this disease.

Methods: We report the case of a 59-year-old woman who presented a vertebrobasilar stroke secondary to infiltration and severe stenosis of the basilar artery, improved after interferon-alpha therapy. We performed a review of the relevant literature and reported the few other cases described.

Results: With our patient, we have found only 7 observations of cerebrovascular disorder in ECD. Most of them had supravascular arteries involvement.

Conclusion: Stroke is a rare treatable and potentially reversible complication of ECD. The pathophysiological processes explaining stroke in this disease are uncertain, but periarterial stenosis of cerebral arteries may be a mechanism.
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http://dx.doi.org/10.1097/MD.0000000000004813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023919PMC
September 2016

Direct stroke unit admission of intravenous tissue plasminogen activator: safety, clinical outcome, and hospital cost savings.

Ther Adv Neurol Disord 2016 Jul 15;9(4):304-9. Epub 2016 May 15.

Stroke Team and Mobile Stroke Unit, University of Tennessee Health Science Center, Memphis, TN, USA.

Background: In the USA, stable intravenous tissue plasminogen activator (IV tPA) patients have traditionally been cared for in an intensive care unit (ICU). We examined the safety of using an acuity-adaptable stroke unit (SU) to manage IV tPA patients.

Methods: We conducted an observational study of consecutive patients admitted to our acuity-adaptable SU over the first 3 years of operation. Safety was assessed by symptomatic intracerebral hemorrhage (sICH) rates, systemic hemorrhage (SH) rates, tPA-related deaths, and transfers from SU to ICU; cost savings and length of stay (LOS) were determined.

Results: We admitted 333 IV tPA patients, of which 302 were admitted directly to the SU. A total of 31 (10%) patients had concurrent systemic hemodynamic or pulmonary compromise warranting direct ICU admission. There were no differences in admission National Institutes of Health Stroke Scale scores between SU and ICU patients (9.0 versus 9.5, respectively). Overall sICH rate was 3.3% (n = 10) and SH rate was 2.9 (n = 9), with no difference between SU and ICU patients. No tPA-related deaths occurred, and no SU patients required transfer to the ICU. Estimated hospital cost savings were US$362,400 for 'avoided' ICU days, and hospital LOS decreased significantly (p = 0.001) from 9.8 ± 15.6 days (median 5) in year 1, to 5.2 ± 4.8 days (median 3) by year 3.

Conclusions: IV tPA patients may be safely cared for in a SU when nurses undergo extensive education to ensure clinical competence. Use of the ICU solely for monitoring may constitute significant overuse of system resources at an expense that is not associated with additional safety benefit.
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http://dx.doi.org/10.1177/1756285616648061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4916527PMC
July 2016

Emerging Risk Factors for Dementia: The Role of Blood Pressure Variability.

CNS Neurol Disord Drug Targets 2016 ;15(6):672-7

Neurology Unit, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 200, Roma 00128, Italy.

In the recent years, classical vascular risk factors have been suggested to play a role also in the development of degenerative dementia. Arterial hypertension has been implicated in the pathogenesis of dementia but no conclusive results have been produced yet; more recently, blood pressure variability (BPV) has been suggested as a more important risk factor for both silent brain vascular lesions and the development of dementia. Blood pressure variability is defined as the variation in blood pressure over time, measured on different time spans and in different ways. We reviewed current scientific literature about the role of BPV in the pathogenesis of dementia, and about the association of abnormal BPV patterns and different forms of dementia. We also suggested some hypothetical pathogenic mechanisms.
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http://dx.doi.org/10.2174/1871527315666160518124101DOI Listing
October 2017

Risk of pneumonia associated with zero-degree head positioning in acute ischemic stroke patients treated with intravenous tissue plasminogen activator.

Brain Behav 2016 02 19;6(2):e00425. Epub 2016 Jan 19.

Department of Neurology University of Tennessee Health Science Center Memphis Tennessee; Australian Catholic University Sydney New South Wales.

Introduction: In the hyperacute phase of ischemic stroke, a 0° position is recommended to increase cerebral perfusion in nonhypoxic patients able to tolerate lying flat. However, use of 0° positioning is not uniformly applied in clinical practice, most likely due to concerns of aspiration pneumonia. We aimed to determine the risk of pneumonia associated with 0° head of bed positioning in acute stroke patients treated with thrombolytic therapy.

Methods: A retrospective descriptive study was conducted using prospectively collected, consecutive acute ischemic stroke patients treated with IVtPA whose head of bed was positioned at 0° for the first 24 h. Rates of hospital-acquired pneumonia were determined using a strict adjudication process to insure accuracy of pneumonia diagnoses. Quantitative characteristics were analyzed in SPSS to compare differences between "true" pneumonia cases and nonpneumonia cases.

Results: Twenty-four of 333 (7.2%) patients had mention the diagnosis of pneumonia in the registry and/or medical record. Of these cases, only 15 (4.5%) met evidence-based diagnostic criteria for hospital-acquired pneumonia. The 15 adjudicated cases had similar median admission NIHSS scores to nonpneumonia cases (10 vs. 9, respectively; P = ns), but were older (74 ± 15 vs. 64 ± 17 years; mean difference 9.889, 95 CI = 1.2-18.6; P = 0.026). A total of eight patients with pneumonia were intubated and mechanically ventilated, and one patient received bilevel positive airway pressure ventilation during the 0° positioning period. Pneumonia cases had significantly longer hospitalizations (14.5 ± 12 vs. 6.6 ± 9 days; mean difference 7.97, 95% CI = 1.1-14.8; P = 0.026) and higher median discharge mRS score (4 vs. 3: P = 0.003).

Conclusions: Zero-degree head of bed positioning in the first 24 h following an acute ischemic stroke treated with IV-tPA was associated with acceptable rates of pneumonia. Rates for pneumonia may be further reduced by eliminating use of a 0° protocol in intubated/mechanically ventilated patients.
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http://dx.doi.org/10.1002/brb3.425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834933PMC
February 2016

Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome after bilateral carotid paraganglioma resection: A case report.

Cephalalgia 2017 Jan 11;37(1):89-93. Epub 2016 Jul 11.

1 Department of Neurology, CHU Poitiers, University of Poitiers, 2 rue de la Milétrie, 86021 Poitiers, France.

Background Paraganglioma is a rare neuroendocrine tumour arising anywhere along the paravertebral sympathetic and parasympathetic chains. In the neck, paraganglioma may affect the carotid body (carotid body tumour). Case report We describe a 43-year-old woman who presented with a reversible vasoconstriction syndrome associated with a posterior reversible encephalopathy syndrome following a surgery for a left carotid paraganglioma (with a past medical history of surgery for a right carotid paraganglioma a few months before). Conclusion A consequence of a baroreflex modification is discussed in order to explain the rare occurrence of such symptoms.
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http://dx.doi.org/10.1177/0333102416629235DOI Listing
January 2017

Elevation of Plasma 2-Arachidonoylglycerol Levels in Alzheimer's Disease Patients as a Potential Protective Mechanism against Neurodegenerative Decline.

J Alzheimers Dis 2015 ;46(2):497-506

Background: Growing evidence suggests that the endocannabinoid system is involved in the pathogenesis of Alzheimer's disease (AD) and atherosclerosis.

Objective: The purpose of this study was to investigate the activation of the endocannabinoid system in AD in vivo and the possible intermediate role of atherosclerosis.

Methods: We enrolled 41 patients with probable AD, and 30 age- and gender-matched controls. All subjects underwent: ultrasound examination of cerebral and neck vessels (including intima-media thickness and plaque stenosis evaluation); blood sampling to measure levels of endocannabinoid [anandamide (AEA), 2-arachidonoylglycerol (2-AG)] and endogenous AEA analogues [N-palmitoyl-ethanolamide (PEA); N-oleoyl-ethanolamide]; neuropsychological evaluation and brain MRI (atrophy, white matter hyperintensity volume).

Results: 2-AG levels were higher in AD patients compared to controls (Mann-Whitney test p = 0.021). In the AD group, 2-AG correlated to white matter hyperintensity volume (r = 0.415, p = 0.015) and was higher in patients with chronic heart ischemic disease (p = 0.023). In AD patients, 2-AG was also positively related to memory (r = 0.334, p = 0.05) and attention (r = 0.423, p = 0.018) performances. Constructional praxia test scores were lower in patients with higher levels of PEA (r =-0.389, p = 0.019).

Conclusion: AD patients present high plasma 2-AG levels, also in relation to heart ischemic disease and cerebral leukoaraiosis. This may be a protective mechanism hindering neurodegeneration, but it may also play an ambivalent role on cerebrovascular circulation. The increase in 2-AG and PEA levels observed with ongoing pathological processes may differently modulate cognitive performances.
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http://dx.doi.org/10.3233/JAD-142349DOI Listing
July 2016

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

Cerebrovasc Dis 2015 24;39(1):23-30. Epub 2014 Dec 24.

Neurology Unit, Università Campus Bio-Medico di Roma, Rome, Italy.

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.
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http://dx.doi.org/10.1159/000369292DOI Listing
October 2015

Do billing codes accurately capture intravenous tissue plasminogen activator treatment rates? Justified concern for clinical performance measures based on billing code assignment.

J Stroke Cerebrovasc Dis 2015 Feb 10;24(2):327-9. Epub 2014 Dec 10.

Health Outcomes Institute, Fountain Hills, Arizona; Australian Catholic University, Sydney, Australia.

Background: International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes are commonly used to determine US national stroke volume and intravenous (IV) tissue plasminogen activator (tPA) treatment rates; however, this method is often criticized because of assumed poor validity and reliability of coding assignment. We sought to understand the validity of IV tPA ICD-9-CM code assignments within a comprehensive stroke center in the southeastern United States.

Methods: Confirmed stroke registry IV tPA cases were retrieved from 2009 to 2011; tPA drip and ship cases were eliminated from the analysis. Retained clinical data included admission National Institutes of Health Stroke Scale (NIHSS) scores, hemorrhagic transformation, diffusion positive magnetic resonance imaging (MRI) results, and discharge modified Rankin Scale (mRS) score.

Results: A total of 247 IV tPA cases were assembled, of which 78% were appropriately assigned the IV tPA billing code. ICD-9 code 434.91 (cerebral artery occlusion with infarct) was used for 72% of the sample, 434.11 (cerebral emboli with infarct) was used for 9% of cases, and 433.11 (carotid occlusion with infarct) was assigned to 2% of cases. Interestingly, 435 (transient cerebral ischemia) was assigned to 2% (n = 7) with all of these cases having NIHSS score more than 2 at time of treatment, diffusion MRI documentation of infarction in 29%, and 43% having a discharge mRS score more than 2.

Conclusions: Our findings support the concern that billing codes may significantly underestimate actual IV tPA treatment volume in the United States and suggest the need for regular audit of billing codes by Stroke Center leaders, with provision of feedback and education to coders, aimed at improving code assignment.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.08.024DOI Listing
February 2015

Cerebrovascular reactivity predicts stroke in high-grade carotid artery disease.

Neurology 2014 Oct 12;83(16):1424-31. Epub 2014 Sep 12.

From the Department of Neurology (M.R., A.H.) and the Institute of Medical Biometry and Statistics (G.S., E.M.), University of Freiburg, Germany; Basel Institute for Clinical Epidemiology and Biostatistics (M.B.), University Hospital Basel, Switzerland; the Department of Clinical Epidemiology and Biostatistics (M.B.), McMaster University, Hamilton, Canada; Neurology Unit (C.A., P.P., F.V.), Università Campus Bio-Medico of Rome, Italy; School of Public Health (A.K.), Imperial College London, UK; the Department of Neurology (N.M.B.), Tel Aviv Sourasky Medical Center and Tel Aviv University, Israel; Columbia University Medical Center (N.P., R.S.M.), Neurological Institute of New York; the Department of Neurology and Neurosurgery (C.J.M.K.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; the Department of Experimental and Clinical Medicine (M.S.), Marche Polytechnic University, Ancona, Italy; and Clinical Neurosciences (H.S.M.), University of Cambridge, UK.

Objective: To assess the usefulness of transcranial Doppler CO2 reactivity (CO2R) for prediction of ipsilateral ischemic stroke in carotid artery stenosis and occlusion with a meta-analysis of prospective studies based on individual patient data.

Methods: We searched Medline, Biosis Previews, Science Citation Index, The Cochrane Library, and EMBASE for studies in which patients with severe carotid artery stenosis or occlusion underwent Doppler CO2R testing (inhalation of CO2 or breath-holding) and were prospectively followed for ipsilateral ischemic stroke. Individual data from 754 patients from 9 studies were included. We used percentage cerebral blood flow velocity increase (pCi) during hypercapnia as the primary CO2R measure, and defined impaired reactivity as pCi <20% increase.

Results: In a multiple regression model, impaired CO2R was independently associated with an increased risk of ipsilateral ischemic stroke (hazard ratio [HR] 3.69; confidence interval [CI] 2.01, 6.77; p < 0.0001). Risk prediction was similar for recently symptomatic vs asymptomatic patients. Using continuous values of pCi, a significant association between decreasing pCi and increasing risk of ipsilateral stroke was found: HR of 1.64 (95% CI 1.33, 2.02; p < 0.0001) per 10% decrease in pCi. For patients with asymptomatic internal carotid artery stenosis only (n = 330), a comparable stroke risk prediction was found: increasing HR 1.95 (95% CI 1.26, 3.04; p = 0.003) per 10% decrease in pCi.

Conclusions: This analysis supports the usefulness of CO2R in risk prediction for patients with severe carotid artery stenosis or occlusion, both in recently symptomatic and asymptomatic patients. Further studies should evaluate whether treatment strategies in asymptomatic patients based on CO2R could improve patient outcomes.
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http://dx.doi.org/10.1212/WNL.0000000000000888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4206163PMC
October 2014

Investigating the utility of previously developed prediction scores in acute ischemic stroke patients in the stroke belt.

J Stroke Cerebrovasc Dis 2014 Sep 10;23(8):2001-2006. Epub 2014 Aug 10.

Stroke Center, Department of Neurology, University of Alabama at Birmingham.

Background: To assess the utility of previously developed scoring systems, we compared SEDAN, named after the components of the score (baseline blood Sugar, Early infarct signs and (hyper) Dense cerebral artery sign on admission computed tomography scan, Age, and National Institutes of Health Stroke Scale on admission), Totaled Health Risks in Vascular Events (THRIVE), Houston Intra-arterial Therapy (HIAT), and HIAT-2 scoring systems among patients receiving systemic (intravenous [IV] tissue plasminogen activator [tPA]) and endovascular (intra-arterial [IA]) treatments.

Methods: We retrospectively reviewed all IV tPA and IA patients presenting to our center from 2008-2011. The scores were assessed in patients who were treated with IV tPA only, IA only, and a combination of IV tPA and IA (IV-IA). We tested the ability of THRIVE to predict discharge modified Rankin scale (mRS) 3-6, HIAT and HIAT-2 discharge mRS 4-6, and SEDAN symptomatic intracerebral hemorrhage (sICH).

Results: Of the 366 patients who were included in this study, 243 had IV tPA only, 89 had IA only, and 34 had IV-IA. THRIVE was predictive of mRS 3-6 in the IV-IA (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.30-2.91) and the IV group (OR, 1.71; 95% CI, 1.43-2.04), but not in the IA group. HIAT was predictive of mRS 4-6 in the IA (OR, 3.55; 95% CI, 1.65-7.25), IV (OR, 3.47; 95% CI, 2.26-5.33), and IV-IA group (OR, 6.48; 95% CI, 1.41-29.71). HIAT-2 was predictive of mRS 4-6 in the IA (OR, 1.39; 95% CI, 1.03-1.87) and IV group (OR, 1.36; 95% CI, 1.18-1.57), but not in the IV-IA group. SEDAN was not predictive of sICH in the IA or the IV-IA group, but was predictive in the IV group (OR, 1.54; 95% CI, 1.01-2.36).

Conclusions: Our study demonstrated that although highly predictive of outcome in the original study design treatment groups, prediction scores may not generalize to all patient samples, highlighting the importance of validating prediction scores in diverse samples.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4780244PMC
September 2014

Acute hyperglycemia reduces cerebrovascular reactivity: the role of glycemic variability.

J Clin Endocrinol Metab 2014 Aug 30;99(8):2854-60. Epub 2014 May 30.

Unit of Endocrinology, Diabetes, and Metabolism (I.G., A.D.F., F.P., I.M., D.Y., S.F.); Department of Neurology (P.Pal., F.P.); and Fatebenefratelli Association for Research Unit of Internal Medicine (S.D., P.Pas.) and Service of Medical Statistics and Information Technology (S.D., P.Pas.), S. Giovanni Calibita Fatebenefratelli Hospital, 00186 Rome, Italy; Department of Systems Medicine (I.G., A.D.F., F.P., I.M., D.Y., D.L., S.F.), University of Rome Tor Vergata, 00133 Rome, Italy; Department of Neurology (P.Pal., R.A., F.V.), Campus Bio-Medico University, 00128 Rome, Italy; and Unit of Health Management (S.D.), Ministry of Health, Viale Giorgio Ribotta 5, 00144 Rome, Italy.

Context: Cerebral vasomotor reactivity (CVR) is reduced in patients with diabetes mellitus (DM), and glucose variability (GV) might be responsible for cerebrovascular damage.

Objective: Studying patients with insulin resistance without DM, we explored the role of GV in impairing CVR.

Patients: We studied 18 metabolic syndrome (MS) patients without DM, 9 controls (C), and 26 patients with DM.

Main Outcome Measures: Groups were compared in terms of CVR, GV, and 24-hour blood pressure. To evaluate the impact of acute hyperglycemia on CVR, a hyperglycemic clamp was performed in MS patients and controls.

Results: Baseline CVR was reduced in DM vs C and MS (C vs DM = 20.2, 95% CI = 3.5-36.9, P = .014; and MS vs DM = 22.2, 95% CI = 8.6-35.8, P = .001), but similar between MS and C (MS vs C = 2.0, 95% CI = -14.7 to 18.7, P = .643). During acute hyperglycemia, CVR fell in MS and C to values comparable to DM. GV progressively increased from C to MS to DM. In MS, CVR at 120 minutes and GV displayed a negative correlation (r = -0.48, P = .043), which did not change after controlling for mean 24-hour systolic and diastolic blood pressure. In MS, the CVR reduction was significantly correlated to GV (r = 0.55, P = .02).

Conclusions: GV is increased in patients with MS but without DM and is the major predictor of CVR reduction induced by acute hyperglycemia, possibly representing the earliest cause of cerebrovascular damage in DM.
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http://dx.doi.org/10.1210/jc.2014-1087DOI Listing
August 2014

Safety of intravenous tissue plasminogen activator administration with computed tomography evidence of prior infarction.

J Stroke Cerebrovasc Dis 2014 Jul 28;23(6):1657-61. Epub 2014 Mar 28.

Stroke Center, Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama.

Background: Prior stroke within 3 months excludes patients from thrombolysis; however, patients may have computed tomography (CT) evidence of prior infarct, often of unknown time of origin. We aimed to determine if the presence of a previous infarct on pretreatment CT is a predictor of hemorrhagic complications and functional outcomes after the administration of intravenous (IV) tissue plasminogen activator (tPA).

Methods: We retrospectively analyzed consecutive patients treated with IV tPA at our institution from 2009-2011. Pretreatment CTs were reviewed for evidence of any prior infarct. Further review determined if any hemorrhagic transformation (HT) or symptomatic intracerebral hemorrhage (sICH) were present on repeat CT or magnetic resonance imaging. Outcomes included sICH, any HT, poor functional outcome (modified Rankin Scale score of 4-6), and discharge disposition.

Results: Of 212 IV tPA-treated patients, 84 (40%) had evidence of prior infarct on pretreatment CT. Patients with prior infarcts on CT were older (median age, 72 versus 65 years; P=.001) and had higher pretreatment National Institutes of Health Stroke Scale scores (median, 10 versus 7; P=.023). Patients with prior infarcts on CT did not experience more sICH (4% versus 2%; P=.221) or any HT (18% versus 14%; P=.471). These patients did have a higher frequency of poor functional outcome at discharge (82% versus 50%; P<.001) and were less often discharged to home or inpatient rehabilitation center (61% versus 73%; P=.065).

Conclusions: Visualization of prior infarcts on pretreatment CT did not predict an increased risk of sICH in our study and should not be viewed as a reason to withhold systemic tPA treatment after clinically evident strokes within 3 months were excluded.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4780218PMC
July 2014

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

Brain Stimul 2014 Mar-Apr;7(2):281-6. Epub 2014 Jan 1.

Neurology Unit, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 200, Rome 00128, Italy.

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.
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http://dx.doi.org/10.1016/j.brs.2013.12.014DOI Listing
May 2015

Racial disparities in early mortality in 1,134 young patients with acute stroke.

Neurol Sci 2014 Jul 28;35(7):1041-9. Epub 2014 Jan 28.

Second Department of Neurology, School of Medicine, "Attikon" Hospital, University of Athens, Iras 39, Gerakas Attikis, 15344, Athens, Greece,

We sought to investigate potential racial disparities in early outcomes of young individuals with stroke in an international multicenter study. We evaluated consecutive patients with first-ever acute stroke aged 18-45 years from prospective databases involving 12 tertiary-care stroke centers in North America (n = 2), Europe (n = 6), and Asia (n = 4). Demographics, vascular risk factors, stroke subtypes, pre-stroke functional status, stroke severity, blood pressure parameters, and serum glucose at hospital admission were documented. The outcome events of interest were 30-day mortality and 30-day favorable functional outcome (FFO) defined as modified-Rankin Scale score of 0-1. A total of 1,134 young adults (mean age 37.4 ± 7.0 years; 58.8 % men; 48.6 % Whites, 23.9 % Blacks, and 27.5 % Asians; median baseline National Institutes of Health Stroke Scale score 6 points, interquartile range 2-13) were included in the analyses. The 30-day stroke mortality and FFO rates differed (p < 0.001) across races. After adjusting for potential confounders, race was independently associated with 30-day mortality (p = 0.026) and 30-day FFO (p = 0.035). Blacks had a fourfold higher odds of 30-day stroke mortality in comparison to Asians (OR 4.00; 95 % CI 1.38-11.59; p = 0.011). Whites also had an increased likelihood of 30-day stroke mortality in comparison to Asians (OR 3.59; 95 % CI 1.28-10.03; p = 0.015). Blacks had a lower odds of 30-day FFO in comparison to Whites (OR 0.57; 95 % CI 0.35-0.91; p = 0.018). Racial disparities in early outcomes following first-ever stroke in young individuals appear to be independent of other known outcome predictor variables. Whites appear to have higher likelihood of 30-day FFO and Asians have lower odds of 30-day stroke mortality.
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http://dx.doi.org/10.1007/s10072-014-1640-9DOI Listing
July 2014

Cerebral hemodynamics and systemic endothelial function are already impaired in well-controlled type 2 diabetic patients, with short-term disease.

PLoS One 2013 31;8(12):e83287. Epub 2013 Dec 31.

Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita Fatebenefratelli Hospital, University of Rome Tor Vergata, Rome, Italy.

Objective: Impaired cerebral vasomotor reactivity (VMR) and flow-mediated dilation (FMD) were found in selected subgroups of type 2 diabetes mellitus (T2DM) patients with long-term disease. Our study aimed to evaluate cerebral hemodynamics, systemic endothelial function and sympatho-vagal balance in a selected population of well-controlled T2DM patients with short-term disease and without cardiac autonomic neuropathy (CAN).

Research Design And Methods: Twenty-six T2DM patients with short-term (4.40±4.80 years) and well-controlled (HbA1C = 6.71±1.29%) disease, without any complications, treated with diet and/or metformin, were consecutively recruited. Eighteen controls, comparable by sex and age, were enrolled also.

Results: FMD and shear rate FMD were found to be reduced in T2DM subjects with short-term disease (8.5% SD 3.5 and 2.5 SD 1.3, respectively) compared to controls (15.4% SD 4.1 and 3.5 SD 1.4; p<.001 and p<.05). T2DM patients also displayed reduced VMR values than controls (39.4% SD 12.4 vs 51.7%, SD 15.5; p<.05). Sympatho-vagal balance was not different in T2DM patients compared to healthy subjects. FMD and shear rate FMD did not correlate with VMR in T2DM patients or in controls (p>.05).

Conclusions: In well-controlled T2DM patients with short-term disease cerebral hemodynamics and systemic endothelial function are altered while autonomic balance appeared to be preserved.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083287PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877017PMC
August 2014

Basilar artery thrombus vs. fenestration: a differential diagnostic challenge in acute ischemic stroke.

J Neuroimaging 2014 Nov-Dec;24(6):607-609. Epub 2013 Nov 19.

Department of Neurology, School of Medicine, University of Alabama Hospital, Birmingham, AL.

We present a case of a man presenting with vertigo and nausea who was found to have multifocal infarcts in the posterior circulation on magnetic resonance imaging (MRI). An magnetic resonance angiography (MRA) demonstrated focal widening and central signal dropout in the distal vertebral artery consistent with arterial fenestration. Transcranial Doppler ultrasonography showed turbulent flow and a spike waveform suggestive of an intra-luminal thrombus. This was confirmed by computed tomography (CT) angiography. Following the initiation of dual antiplatelet therapy, the signal abnormalities on transcranial doppler (TCD) resolved suggesting dissolution of the thrombus. This case highlights the diagnostic pitfalls that may arise when relying on only one modality for assessing intracranial vasculature and the importance of clarifying the diagnosis of basilar thrombosis or fenestration.
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http://dx.doi.org/10.1111/jon.12069DOI Listing
August 2015

Hypercapnia affects the functional coupling of resting state electroencephalographic rhythms and cerebral haemodynamics in healthy elderly subjects and in patients with amnestic mild cognitive impairment.

Clin Neurophysiol 2014 Apr 15;125(4):685-693. Epub 2013 Nov 15.

Unità di Neurologia, Università Campus Bio-Medico di Roma, Rome, Italy.

Objective: Cerebral vasomotor reactivity (VMR) and coherence of resting state electroencephalographic (EEG) rhythms are impaired in Alzheimer's disease (AD) patients. Here we tested the hypothesis that these two variables could be related.

Methods: We investigated VMR and coherence of resting state EEG rhythms in nine normal elderly (Nold) and in 10 amnesic mild cognitive impairment (MCI) subjects. Resting state eyes-closed EEG data were recorded at baseline pre-CO₂ (ambient air, 2 min), during 7% CO₂/air mixture inhalation (hypercapnia, 90 s) and post-CO₂ (ambient air, 2 min) conditions. Simultaneous frontal bilateral near-infrared spectroscopy (NIRS) was performed to assess VMR by cortical oxy- and deoxy-haemoglobin concentration changes. EEG coherence across all electrodes was computed at delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz) and gamma (30-40 Hz) bands.

Results: In Nold subjects, 'total coherence' of EEG across all frequency bands and electrode pairs decreased during hypercapnia, with full recovery during post-CO₂. Total coherence resulted lower in pre-CO₂ and post-CO₂ and presented poor reactivity during CO₂ inhalation in MCI patients compared with Nold subjects. Hypercapnia increased oxy-haemoglobin and decreased deoxy-haemoglobin concentrations in both groups. Furthermore, the extent of changes in these variables during CO₂ challenge was correlated with the EEG coherence, as a reflection of neurovascular coupling.

Conclusions: Hypercapnia induced normal frontal VMR that was detected by NIRS in both Nold and amnesic MCI groups, while it produced a reactivity of global functional coupling of resting state EEG rhythms only in the Nold group.

Significance: In amnesic MCI patients, global EEG functional coupling is basically low in amplitude and does not react to hypercapnia.
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http://dx.doi.org/10.1016/j.clinph.2013.10.002DOI Listing
April 2014

Allergens in allergy diagnosis: a glimpse at emerging new concepts and methodologies.

Transl Med UniSa 2012 Sep 11;4:27-33. Epub 2012 Oct 11.

Institute of Protein Biochemistry, CNR, Naples, Italy ; Center for Molecular Allergology, IDI-IRCCS, Rome, Italy.

Allergic diseases are important concern of public health. A reliable diagnosis is of utmost importance for the management of allergic patients both when immunotherapy is planned and when the treatment is essentially based on the avoidance of the allergy source. However, the available diagnostic systems sometimes fail to detect specific IgE antibodies thus impairing the correct diagnosis. The traditional test systems are generally based on the use of protein extracts derived from the allergenic sources whose composition is very variable and cannot be standardized. The development of a new methodology combining the so-called allergenic molecule-based diagnosis with the multiplex microarray technology and allowing the analysis of multiple purified allergens in a single test represents an important improvement in allergy diagnosis. In addition, the biochemical and immunological characterisation of individual allergens has provided new insights into the understanding of allergen-IgE recognition that could be exploited for further improvements of allergy diagnostic tests.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728798PMC
September 2012

Wheat IgE profiling and wheat IgE levels in bakers with allergic occupational phenotypes.

Occup Environ Med 2013 Sep 17;70(9):617-22. Epub 2013 May 17.

Unit of Occupational Medicine, Department of Public Health and Community Medicine, University of Verona, Verona, Italy.

Objectives: To characterise occupational wheat allergic phenotypes (rhino-conjunctivitis, asthma and dermatitis) and immunoglobulin (IgE) sensitisation to particular wheat allergens in bakers.

Methods: We conducted clinical and immunological evaluations of 81 consecutive bakers reporting occupational symptoms using commercial tests (skin prick test (SPT), specific IgE, ISAC microarray) and six additional dot-blotted wheat allergens (Tri a 39, Tri a Trx, Tri a GST, Tri a 32, Tri a 12, Tri a DH).

Results: Wheat SPT resulted positive in 29 bakers and was associated with work-related asthma (p<0.01). Wheat IgE was detected in 51 workers and was associated with work-related asthma (p<0.01) and rhino-conjunctivitis (p<0.05). ISAC Tri a 30 was positive in three workers and was associated with work-related dermatitis (p<0.05). Wheat dot-blotted allergens were positive in 22 bakers. Tri a 32 and Tri a GST were positive in 13 and three bakers, respectively, and both were associated with work-related dermatitis (p<0.05). This association increased (p<0.01) when Tri a 32, Tri a GST and Tri a 30 were analysed together (p<0.01). Wheat IgE levels were associated with work-related dermatitis (p<0.01).

Conclusions: Wheat IgE levels and wheat microarrayed allergens may be associated with some occupational allergic phenotypes. The extension of the panel of wheat allergens may be promising for discriminating the clinical manifestations of baker's allergy.
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http://dx.doi.org/10.1136/oemed-2012-101112DOI Listing
September 2013

Diffusion-weighted lesions after carotid artery stenting are associated with cognitive impairment.

J Neurol Sci 2013 May 17;328(1-2):58-63. Epub 2013 Mar 17.

Neurology Unit, Università Campus Bio-Medico di Roma, Italy.

The effect of carotid artery stenting (CAS) on cognitive function is still debated. Cerebral microembolism, detectable by post-procedural diffusion-weighted imaging (DWI) lesions, has been suggested to predispose to cognitive decline. Our study aimed at evaluating the effect of CAS on cognitive profile focusing on the potential role of cerebral microembolic lesions, taking into consideration the impact of factors potentially influencing cognitive status (demographic features, vascular risk profile, neuropsychological evaluation at baseline and magnetic resonance (MR) markers of brain structural damage). Thirty-seven patients with severe carotid artery stenosis were enrolled. Neurological assessment, neuropsychological evaluation and brain MR were performed the day before CAS (E0). Brain MR with DWI was repeated the day after CAS (E1), while neuropsychological evaluation was done after a 14-month median period (E2). Volumes of both white matter hyperintensities and whole brain were estimated at E0 on axial MR FLAIR and T1w-SE sequences, respectively. Unadjusted ANOVA analysis showed a significant CAS*DWI interaction for MMSE (F=7.154(32), p=.012). After adjusting for factors potentially influencing cognitive status CAS*DWI interaction was confirmed for MMSE (F=7.092(13), p=.020). Patients with DWI lesions showed a mean E2-E0 MMSE reduction of -3.1, while group without DWI lesions showed a mean E2-E0 MMSE of +1.1. Our study showed that peri-procedural brain microembolic load impacts negatively on cognitive functions, independently from the influence of patients-related variables.
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http://dx.doi.org/10.1016/j.jns.2013.02.019DOI Listing
May 2013

Lack of correlation between cerebral vasomotor reactivity and flow-mediated dilation in subjects without vascular disease.

Ultrasound Med Biol 2013 Jan 8;39(1):10-5. Epub 2012 Nov 8.

Neurologia Clinica, Università Campus Bio-Medico, Rome, Italy.

Cerebral vasomotor reactivity (CVR) represents the capability of cerebral vessels to modify their caliber in response to a stimulus. Impaired CVR is associated with an increased risk for ischemic events in patients with carotid disease. Endothelial dysfunction is considered an important pathogenic factor for atherosclerosis and can be noninvasively assessed by flow-mediated vasodilation (FMD) evaluation. We aimed to evaluate both CVR and FMD in patients without histories of vascular disease in order to define a possible correlation. FMD was measured as brachial artery flow and diameter changes induced by transient ischemia. CVR to hypercapnia was assessed in all subjects by means of a breath-holding test and, in 20 subjects, by an additional CO(2) inhalation test. In 30 healthy volunteers (60% women, mean age 56 ± 6 years), CVR and FMD did not appear to be correlated (p = 0.444). A strong association between CO(2)-induced CVR and breath-holding index was observed (p < 0.001). CVR and FMD represent 2 different modalities that evaluate vasomotor function. According to our data, they did not appear to correlate, probably due to physiologic differences between cerebral and peripheral vascular districts and the vasodilatory stimulus used. The carbon dioxide-induced CVR and breath-holding index appeared to be significantly associated.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2012.08.022DOI Listing
January 2013

Tolerability of a fully maturated cheese in cow's milk allergic children: biochemical, immunochemical, and clinical aspects.

PLoS One 2012 19;7(7):e40945. Epub 2012 Jul 19.

Center for Molecular Allergology, IDI-IRCCS, Rome, Italy.

Background: From patients' reports and our preliminary observations, a fully maturated cheese (Parmigiano-Reggiano; PR) seems to be well tolerated by a subset of cow's milk (CM) allergic patients.

Objective And Methods: To biochemically and immunologically characterize PR samples at different maturation stage and to verify PR tolerability in CM allergic children. Seventy patients, with suspected CM allergy, were enrolled. IgE to CM, α-lactalbumin (ALA), β-lactoglobulin (BLG) and caseins (CAS) were tested using ImmunoCAP, ISAC103 and skin prick test. Patients underwent a double-blind, placebo-controlled food challenge with CM, and an open food challenge with 36 months-maturated PR. Extracts obtained from PR samples were biochemically analyzed in order to determine protein and peptide contents. Pepsin and trypsin-chymotrypsin-pepsin simulated digestions were applied to PR extracts. Each PR extract was investigated by IgE Single Point Highest Inhibition Achievable assay (SPHIAa). The efficiency analysis was carried out using CM and PR oral challenges as gold standards.

Results: The IgE binding to milk allergens was 100% inhibited by almost all PR preparations; the only difference was for CAS, mainly α(S1)-CAS. Sixteen patients sensitized to CM tolerated both CM and PR; 29 patients tolerated PR only; 21 patients, reacted to both CM and PR, whereas 4 patients reactive to CM refused to ingest PR. ROC analysis showed that the absence of IgE to BLG measured by ISAC could be a good marker of PR tolerance. The SPHIAa using digested PR preparations showed a marked effect on IgE binding to CAS and almost none on ALA and BLG.

Conclusions: 58% of patients clinically reactive to CM tolerated fully maturated PR. The preliminary digestion of CAS induced by PR maturation process, facilitating a further loss of allergenic reactivity during gut digestion, might explain the tolerance. This hypothesis seems to work when no IgE sensitization to ISAC BLG is detected.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0040945PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400663PMC
December 2012

Headache and aphasia in a young woman with protein S deficiency and nephrotic syndrome.

Acta Clin Croat 2011 Dec;50(4):619-21

Comprehensive Stroke Center, University of Alabama Hospital, Birmingham, AL, USA.

We present sequential brain imaging findings in a young woman who while being evaluated for a newly discovered nephrotic syndrome developed headache followed by aphasia. The patient's symptoms were due to cerebral venous thrombosis in the setting of protein S deficiency and oral contraception.
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December 2011
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