Publications by authors named "Alessandro Biffi"

129 Publications

Relationship Between Cardiorespiratory Fitness, Baseline Blood Pressure and Hypertensive Response to Exercise in the Ferrari Corporate Population.

High Blood Press Cardiovasc Prev 2021 Nov 25. Epub 2021 Nov 25.

Cardiology Unit, Department of Clinical and Molecular Medicine, School of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.

Aim: To evaluate the incidence and clinical significance of impaired cardiorespiratory fitness (CRF) and the association with baseline blood pressure (BP) levels and hypertensive response to exercise (HRE).

Methods: A cross-sectional study was conducted on a total sample of 2058 individuals with a mean age of 38 ± 9 years, enrolled for the first time at the Ferrari corporate wellness program "Formula Benessere", including a maximal exercise stress testing (EST). BP and heart rate (HR) values were obtained from EST at rest, during exercise and recovery time. CRF was arbitrarily classified according to estimated VO in optimal, normal, mildly and moderately reduced.

Results: One-hundred and thirty-nine individuals of 2058 (6.7%) showed a moderate CRF reduction assessed by EST. Subjects with elevated resting and/or exercise BP showed a worse CRF than those with normal BP levels, also after the adjustment for age, sex, body mass index, smoking habits, peak SBP and DBP. Seventy-seven individuals (3.7%) showed an HRE during EST, with normal baseline BP levels.

Conclusion: About 7% of a corporate population showed a significantly reduced CRF, assessed by EST. Individuals with lower levels of CRF have higher resting and/or peak exercising BP values after adjusting for co-variables. This study expands the role of EST outside of traditional ischemic CVD evaluation, towards the assessment of reduced CRF and HRE in the general population, as a possible not evaluated CV risk factor.
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http://dx.doi.org/10.1007/s40292-021-00491-5DOI Listing
November 2021

Cases of Neuroinfectious Disease Highlighting Frontotemporal Neurocircuitry in Cognitive and Affective Processing.

Prim Care Companion CNS Disord 2021 Nov 4;23(6). Epub 2021 Nov 4.

Division of Neuropsychiatry, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts.

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http://dx.doi.org/10.4088/PCC.20cr02894DOI Listing
November 2021

Cerebral Small Vessel Disease and Depression Among Intracerebral Hemorrhage Survivors.

Stroke 2021 Sep 30:STROKEAHA121035488. Epub 2021 Sep 30.

Department of Neurology, Massachusetts General Hospital, Boston. (J.P.C., M.P., P.K., J.R.A., A.C., C.K., Z.D., K.S., C.D.A., M.E.G., S.M.G., J.R., A.V., A.B.).

Background And Purpose: Intracerebral hemorrhage (ICH) is an acute manifestation of cerebral small vessel disease (CSVD), usually cerebral amyloid angiopathy or hypertensive arteriopathy. CSVD-related imaging findings are associated with increased depression incidence in the general population. Neuroimaging may, therefore, provide insight on depression risk among ICH survivors. We sought to determine whether CSVD CT and magnetic resonance imaging markers are associated with depression risk (before and after ICH), depression remission, and effectiveness of antidepressant treatment.

Methods: We analyzed data from the single-center longitudinal ICH study conducted at Massachusetts General Hospital. Participants underwent CT and magnetic resonance imaging imaging and were followed longitudinally. We extracted information for neuroimaging markers of CSVD subtype and severity. Outcomes of interest included pre-ICH depression, new-onset depression after ICH, resolution of depressive symptoms, and response to antidepressant treatment.

Results: We followed 612 ICH survivors for a median of 47.2 months. Multiple CSVD-related markers were associated with depression risk. Survivors of cerebral amyloid angiopathy-related lobar ICH were more likely to be diagnosed with depression before ICH (odds ratio, 1.68 [95% CI, 1.14-2.48]) and after ICH (sub-hazard ratio, 1.52 [95% CI, 1.12-2.07]), less likely to achieve remission of depressive symptoms (sub-hazard ratio, 0.69 [95% CI, 0.51-0.94]), and to benefit from antidepressant therapy (=0.041). Cerebral amyloid angiopathy disease burden on magnetic resonance imaging was associated with depression incidence and treatment resistance (interaction =0.037), whereas hypertensive arteriopathy disease burden was only associated with depression incidence after ICH.

Conclusions: CSVD severity is associated with depression diagnosis, both before and after ICH. Cerebral amyloid angiopathy-related ICH survivors are more likely to experience depression (both before and after ICH) than patients diagnosed with hypertensive arteriopathy-related ICH, and more likely to report persistent depressive symptoms and display resistance to antidepressant treatment.
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http://dx.doi.org/10.1161/STROKEAHA.121.035488DOI Listing
September 2021

Shedding Light on the Causes and Characteristics of Stroke in Lebanon: A Systematic Review of Literature.

J Geriatr Psychiatry Neurol 2021 Sep 23:8919887211044753. Epub 2021 Sep 23.

Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.

Background: The prevalence and severity of stroke in Lebanon has increased over the past decade and stroke is currently the second leading cause of death in the country.

Methods: We systematically reviewed existing research on stroke prevalence, risk factors, mortality and morbidity of stroke, stroke treatment, and stroke education to assess the epidemiology of stroke in Lebanon. A literature search was conducted on the PubMed database for articles presenting data in any of these 5 categories in Lebanon, as well as articles discussing the Middle East and North Africa region generally.

Results: A high prevalence of modifiable risk factors (cigarette and waterpipe smoking) and risk factors that could be mitigated by lifestyle changes (obesity and hypertension) were found in Lebanon. Stroke mortality rates and risk factors of mortality were consistent with global trends, though the cost of treatment in Lebanon was significantly higher than in other developing nations.

Conclusion: Urgent public health initiatives are needed to educate the public about the dangers of modifiable stroke risk factors and to reduce the burden of stroke in Lebanon.
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http://dx.doi.org/10.1177/08919887211044753DOI Listing
September 2021

Idiopathic primary intraventricular hemorrhage and cerebral small vessel disease.

Int J Stroke 2021 Sep 10:17474930211043957. Epub 2021 Sep 10.

Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Background: Although primary intraventricular hemorrhage is frequently due to trauma or vascular lesions, the etiology of idiopathic primary intraventricular hemorrhage (IP-IVH) is not defined.

Aims: Herein, we test the hypothesis that cerebral small vessel diseases (cSVD) including hypertensive cSVD (HTN-cSVD) and cerebral amyloid angiopathy are associated with IP-IVH.

Methods: Brain magnetic resonance imaging from consecutive patients (January 2011 to September 2019) with non-traumatic intracerebral hemorrhage from a single referral center were reviewed for the presence of HTN-cSVD (defined by strictly deep or mixed-location intracerebral hemorrhage/cerebral microbleeds) and cerebral amyloid angiopathy (applying modified Boston criteria).

Results: Forty-six (4%) out of 1276 patients were identified as having IP-IVH. Among these, the mean age was 74.4 ± 12.2 years and 18 (39%) were females. Forty (87%) had hypertension, and the mean initial blood pressure was 169.2 ± 40.4/88.8 ± 22.2 mmHg. Of the 35 (76%) patients who received a brain magnetic resonance imaging, two (6%) fulfilled the modified Boston criteria for possible cerebral amyloid angiopathy and 10 (29%) for probable cerebral amyloid angiopathy. Probable cerebral amyloid angiopathy was found at a similar frequency when comparing IP-IVH patients to the remaining patients with primary intraparenchymal hemorrhage (P-IPH) (27%,  = 0.85). Furthermore, imaging evidence for HTN-cSVD was found in 8 (24%) patients with IP-IVH compared to 209 (28%,  = 0.52) patients with P-IPH.

Conclusions: Among IP-IVH patients, cerebral amyloid angiopathy was found in approximately one-third of patients, whereas HTN-cSVD was detected in 23%-both similar rates to P-IPH patients. Our results suggest that both cSVD subtypes may be associated with IP-IVH.
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http://dx.doi.org/10.1177/17474930211043957DOI Listing
September 2021

Case 19-2021: A 54-Year-Old Man with Irritability, Confusion, and Odd Behaviors.

N Engl J Med 2021 Jun;384(25):2438-2445

From the Departments of Psychiatry (N.K., M.W.P.), Neurology (A.B.), and Radiology (R.G.G.), Massachusetts General Hospital, and the Departments of Psychiatry (N.K., M.W.P.), Neurology (A.B.), and Radiology (R.G.G.), Harvard Medical School - both in Boston.

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http://dx.doi.org/10.1056/NEJMcpc2100272DOI Listing
June 2021

Neuropsychiatry, Palliative Care, and Culture: What Matters Beyond Diagnosis.

Prim Care Companion CNS Disord 2021 02 24;23(2). Epub 2021 Feb 24.

Division of Palliative Care and Geriatric Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.4088/PCC.20l02610DOI Listing
February 2021

Impact of Uncontrolled Hypertension at 3 Months After Intracerebral Hemorrhage.

J Am Heart Assoc 2021 06 15;10(11):e020392. Epub 2021 May 15.

Department of Neurology Massachusetts General Hospital Boston MA.

Background Survivors of intracerebral hemorrhage (ICH) are at high risk for recurrent stroke, which is associated with blood pressure control. Because most recurrent stroke events occur within 12 to 18 months of the index ICH, rapid blood pressure control is likely to be crucial. We investigated the frequency and prognostic impact of uncontrolled short-term hypertension after ICH. Methods and Results We analyzed data from Massachusetts General Hospital (n=1305) and the University of Hong Kong (n=523). We classified hypertension as controlled, undertreated, or treatment resistant at 3 months after ICH and determined the following: (1) the risk factors for uncontrolled hypertension and (2) whether hypertension control at 3 months is associated with stroke recurrence and mortality. We followed 1828 survivors of ICH for a median of 46.2 months. Only 9 of 234 (4%) recurrent strokes occurred before 3 months after ICH. At 3 months, 713 participants (39%) had controlled hypertension, 755 (41%) had undertreated hypertension, and 360 (20%) had treatment-resistant hypertension. Black, Hispanic, and Asian race/ethnicity and higher blood pressure at time of ICH increased the risk of uncontrolled hypertension at 3 months (all <0.05). Uncontrolled hypertension at 3 months was associated with recurrent stroke and mortality during long-term follow-up (all <0.05). Conclusions Among survivors of ICH, >60% had uncontrolled hypertension at 3 months, with undertreatment accounting for the majority of cases. The 3-month blood pressure measurements were associated with higher recurrent stroke risk and mortality. Black, Hispanic, and Asian survivors of ICH and those presenting with severe acute hypertensive response were at highest risk for uncontrolled hypertension.
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http://dx.doi.org/10.1161/JAHA.120.020392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483505PMC
June 2021

Contribution of Racial and Ethnic Differences in Cerebral Small Vessel Disease Subtype and Burden to Risk of Cerebral Hemorrhage Recurrence.

Neurology 2021 05 21;96(20):e2469-e2480. Epub 2021 Apr 21.

From the Department of Neurology (J.P.C., J.R.A., A.R.-T., S.M., P.K., A.C., C.K., Z.D., K.S., M.E.G., A.V., C.D.A., S.M.G., J.R., A.B.), Hemorrhagic Stroke Research Program (J.P.C., J.R.A., A.R.-T., S.M., P.K., A.C., C.K, Z.D., K.S., M.E.G., A.V., C.D.A., S.M.G., J.R., A.B.), Henry and Allison McCance Center for Brain Health (J.P.C., J.R.A., P.K., C.K., C.D.A., J.R., A.B.), and Center for Genomic Medicine (J.R.A., S.M., P.K., C.K., C.D.A., J.R., A.B.), Massachusetts General Hospital, Boston; University of Lille (M.P.), Inserm, CHU Lille, U1172-LilNCog-Lille Neuroscience & Cognition, France; School of Medicine (A.R.-T.), University of California, Irvine; Department of Neurology and Rehabilitation Medicine (S.D., L.G., M.L.F., D.W.), University of Cincinnati, OH; Department of Biostatistics and Data Sciences (C.D.L.), Wake Forest University, Winston-Salem, NC; Department of Neurology (A.T.), Keck School of Medicine, University of Southern California; and Los Angeles County Department of Health Services (A.T.), CA.

Objective: Black and Hispanic survivors of intracerebral hemorrhage (ICH) are at higher risk of recurrent intracranial bleeding. MRI-based markers of chronic cerebral small vessel disease (CSVD) are consistently associated with recurrent ICH. We therefore sought to investigate whether racial/ethnic differences in MRI-defined CSVD subtype and severity contribute to disparities in ICH recurrence risk.

Methods: We analyzed data from the Massachusetts General Hospital ICH study (n = 593) and the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study (n = 329). Using CSVD markers derived from MRIs obtained within 90 days of index ICH, we classified ICH cases as cerebral amyloid angiopathy (CAA)-related, hypertensive arteriopathy (HTNA)-related, and mixed etiology. We quantified CSVD burden using validated global, CAA-specific, and HTNA-specific scores. We compared CSVD subtype and severity among White, Black, and Hispanic ICH survivors and investigated its association with ICH recurrence risk.

Results: We analyzed data for 922 ICH survivors (655 White, 130 Black, 137 Hispanic). Minority ICH survivors had greater global CSVD ( = 0.011) and HTNA burden ( = 0.021) on MRI. Furthermore, minority survivors of HTNA-related and mixed-etiology ICH demonstrated higher HTNA burden, resulting in increased ICH recurrence risk (all < 0.05).

Conclusions: We uncovered significant differences in CSVD subtypes and severity among White and minority survivors of primary ICH, with direct implication for known disparities in ICH recurrence risk. Future studies of racial/ethnic disparities in ICH outcomes will benefit from including detailed MRI-based assessment of CSVD subtypes and severity and investigating social determinants of health.
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http://dx.doi.org/10.1212/WNL.0000000000011932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205476PMC
May 2021

Italian Cardiological Guidelines (COCIS) for Competitive Sport Eligibility in athletes with heart disease: update 2020.

J Cardiovasc Med (Hagerstown) 2021 Dec;22(12):874-891

Sports Medicine Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome.

Since 1989, SIC Sport and a FMSI, in partnership with leading Italian Cardiological Scientific Associations (ANCE, ANMCO and SIC) have produced Cardiological Guidelines for Completive Sports Eligibility for athletes with heart disease (COCIS -- 1989, 1995, 2003, 2009 and 2017). The English version of the Italian Cardiological Guidelines for Competitive Sports Eligibility for athletes with heart disease was published in 2013 in this Journal. This publication is an update with respect to the document previously published in English in 2013. It includes the principal innovations that have emerged over recent years, and is divided into five main chapters: arrhythmias, ion channel disorders, congenital heart diseases, acquired valve diseases, cardiomyopathies, myocarditis and pericarditis and ischemic heart disease. Wherever no new data have been introduced with respect to the 2013 publication, please refer to the previous version. This document is intended to complement recent European and American guidelines but an important difference should be noted. The European and American guidelines indicate good practice for people engaging in physical activity at various levels, not only at the competitive level. In contrast, the COCIS guidelines refer specifically to competitive athletes in various sports including those with high cardiovascular stress. This explains why Italian guidelines are more restrictive than European and USA ones. COCIS guidelines address 'sports doctors' who, in Italy, must certify fitness to participate in competitive sports. In Italy, this certificate is essential for participating in any competition.
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http://dx.doi.org/10.2459/JCM.0000000000001186DOI Listing
December 2021

Athletes with valvular heart disease and competitive sports: a position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology.

Eur J Prev Cardiol 2021 Apr 13. Epub 2021 Apr 13.

Clinic for General and Interventional Cardiology/Angiology, Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany.

This article provides an overview of the recommendations from the Sports Cardiology section of the European Association of Preventive Cardiology on sports participation in individuals with valvular heart disease (VHD). The aim of these recommendations is to encourage regular physical activity including sports participation, with reasonable precaution to ensure a high level of safety for all affected individuals. Valvular heart disease is usually an age-related degenerative process, predominantly affecting individuals in their fifth decade and onwards. However, there is an increasing group of younger individuals with valvular defects. The diagnosis of cardiac disorders during routine cardiac examination often raises questions about on-going participation in competitive sport with a high dynamic or static component and the level of permissible physical effort during recreational exercise. Although the natural history of several valvular diseases has been reported in the general population, little is known about the potential influence of chronic intensive physical activity on valve function, left ventricular remodelling pulmonary artery pressure, and risk of arrhythmia. Due to the sparsity of data on the effects of exercise on VHD, the present document is largely based on clinical experience and expert opinion.
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http://dx.doi.org/10.1093/eurjpc/zwab058DOI Listing
April 2021

Hematoma Expansion in Intracerebral Hemorrhage With Unclear Onset.

Neurology 2021 05 1;96(19):e2363-e2371. Epub 2021 Apr 1.

From UO Neurologia (A.M.), Azienda Socio-Sanitaria Territoriale (ASST) Valcamonica, Esine, Italy; Neuroradiology Department (G. Boulouis), Centre Hospitalier Sainte-Anne, Paris, France; J.P. Kistler Stroke Research Center, Department of Neurology (A. Charidimou, Q.L., A.D.W., C.D.A., M.E.G., A.B., A.V., S.M.G., J.R., J.N.G.), Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica (L.P., A. Pezzini, A. Padovani), Università degli Studi di Brescia; UO di Neurologia (P.C.), Istituto Clinico Fondazione Poliambulanza, Brescia; UOC Neurologia (V.D.G.), ASST Cremona; UC Malattie Cerebrovascolari e Stroke Unit (E.L., F.M., A. Cavallini) and UC Neurologia d'Urgenza (E.L., F.M., G.M.), IRCCS Fondazione Mondino, Pavia; Dipartimento di Dipartimento di Scienze Biomediche, Sperimentali e Cliniche, Neuroradiologia, Università degliStudi di Firenze (G. Busto, E.F.), and Stroke Unit (F.A., A.Z.), Ospedale Universitario Careggi, Firenze; UOC Neurologia e Rete Stroke, Metropolitana (L.B., S.G.), and Unità di Neuroradiologia (L.S.), IRCCS Istituto delle Scienze Neurologiche di Bologna, Ospedale Maggiore; Clinica Neurologica, Dipartimento di Scienze Biomediche e Chirurgico Specialistiche (M.L., I.C.), Università degli studi diFerrara, Ospedale Universitario S. Anna, Ferrara; Neurologia e Stroke Unit (E.C.), Ospedale di Circolo, ASST Settelaghi, Varese; Stroke Unit (M.G., M.M.), Neurologia Vascolare, ASST Spedali Civili, Brescia, Italy; Division of Neurocritical Care and Emergency Neurology, Department of Neurology (C.D.A., J.R., J.N.G.), Harvard Medical School, Henry and Allison McCance Center for Brain Health (C.D.A., J.R., J.N.G.), and Department of Emergency Medicine (J.N.G.), Massachusetts General Hospital, Boston.

Objective: To investigate the prevalence, predictors, and prognostic effect of hematoma expansion (HE) in patients with intracerebral hemorrhage (ICH) with unclear symptom onset (USO).

Methods: We performed a retrospective analysis of patients with primary spontaneous ICH admitted at 5 academic medical centers in the United States and Italy. HE (volume increase >6 mL or >33% from baseline to follow-up noncontrast CT [NCCT]) and mortality at 30 days were the outcomes of interest. Baseline NCCT was also analyzed for presence of hypodensities (any hypodense region within the hematoma margins). Predictors of HE and mortality were explored with multivariable logistic regression.

Results: We enrolled 2,165 participants, 1,022 in the development cohort and 1,143 in the replication cohort, of whom 352 (34.4%) and 407 (35.6%) had ICH with USO, respectively. When compared with participants having a clear symptom onset, patients with USO had a similar frequency of HE (25.0% vs 21.9%, = 0.269 and 29.9% vs 31.5%, = 0.423). Among patients with USO, HE was independently associated with mortality after adjustment for confounders (odds ratio [OR] 2.64, 95% confidence interval [CI] 1.43-4.89, = 0.002). This finding was similar in the replication cohort (OR 3.46, 95% CI 1.86-6.44, < 0.001). The presence of NCCT hypodensities in patients with USO was an independent predictor of HE in the development (OR 2.59, 95% CI 1.27-5.28, = 0.009) and replication (OR 2.43, 95% CI 1.42-4.17, = 0.001) population.

Conclusion: HE is common in patients with USO and independently associated with worse outcome. These findings suggest that patients with USO may be enrolled in clinical trials of medical treatments targeting HE.
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http://dx.doi.org/10.1212/WNL.0000000000011895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166446PMC
May 2021

EAPC Core Curriculum for Preventive Cardiology.

Eur J Prev Cardiol 2021 04 1. Epub 2021 Apr 1.

Department of Prevention and Sports Medicine, University Hospital rechts der Isar, Technical University Munich, German Centre for Cardiovascular Research, Georg-Brauchle-Ring 56, 80992 Munich, Germany.

Preventive cardiology encompasses the whole spectrum of cardiovascular disease (CVD) prevention, at individual and population level, through all stages of life. This includes promotion of cardiovascular (CV) health, management of individuals at risk of developing CVD, and management of patients with established CVD, through interdisciplinary care in different settings. Preventive cardiology addresses all aspects of CV health in the context of the social determinants of health, including physical activity, exercise, sports, nutrition, weight management, smoking cessation, psychosocial factors and behavioural change, environmental, genetic and biological risk factors, and CV protective medications. This is the first European Core Curriculum for Preventive Cardiology, which will help to standardize, structure, deliver, and evaluate training in preventive cardiology across Europe. It will be the basis for dedicated fellowship programmes and a European Society of Preventive Cardiology (EAPC) subspecialty certification for cardiologists, with the intention to improve quality and outcome in CVD prevention.
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http://dx.doi.org/10.1093/eurjpc/zwab017DOI Listing
April 2021

Usefulness of the corporate wellness projects in primary prevention at the population level: a study on the prevalence, awareness, and control of hypertension in the Ferrari company.

J Hum Hypertens 2021 Mar 23. Epub 2021 Mar 23.

Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.

The aim of our study was to evaluate the prevalence, awareness, and control of hypertension in an apparently healthy company population. We conducted a cross-sectional study on a total sample of 2058 individuals with a mean age of 38 ± 9 years, enrolled for the first time to the Ferrari corporate wellness program "Formula Benessere". Hypertension was defined as systolic blood pressure (SBP) level ≥140 mmHg or diastolic BP (DBP) ≥90 mmHg or use of antihypertensive medication, whereas BP control was defined as BP level <130/80 mmHg. All 2058 participants were divided into three groups based on age: Group 1 aged <40 years (n = 1177, 57%), Group 2 aged 40-50 years (n = 627, 30%), and Group 3 aged >50 years (n = 254, 13%). Four-hundred and one subjects had BP levels ≥130/80 mmHg (19.5%). Two-hundred and sixty-one individuals (12.7%) had high-normal BP values and 140 subjects had rest SBP ≥140 mmHg and/or DBP ≥90 mmHg (6,8%), of which 41 (29.3%) with grade 2 hypertension. In the overall population, 259 individuals (12.5%) were affected by hypertension, the prevalence increasing with age. Only a minority (51%) was aware of being hypertensive and already treated with antihypertensive medications (45.9%). An adequate BP control was achieved in only 57% of subjects who received BP-lowering therapy. Corporate wellness programs may represent an essential tool in identifying apparently healthy subjects with an inadequate control of cardiovascular (CV) risk factors, such as hypertension. These preventive programs in the workplace may help to improve and spread primary CV prevention at the population level.
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http://dx.doi.org/10.1038/s41371-021-00528-1DOI Listing
March 2021

Neuropsychiatric symptoms in a occipito-temporal infarction with remarkable long-term functional recovery.

Cortex 2021 04 6;137:205-214. Epub 2021 Feb 6.

Massachusetts General Hospital, Boston, MA, USA. Electronic address:

Posterior circulation infarctions (PCI) constitute 5-25% of ischemic strokes. PCI of the occipital lobe present with a panoply of symptoms including quadrantanopsia, topographical disorientation, and executive dysfunction. Long-term cognitive recovery after PCI is not well described. However, the adult brain is remarkably plastic, capable of adapting and remodeling. We describe a 43-year-old right-handed woman who complained of black spots in both eyes, headaches, photophobia, and a feeling she would faint. Initial neurological exam and a CT scan were normal; she was diagnosed with ocular migraine. A second neurological exam a week later showed left superior quadrantopsia; an MRI scan suggested right occipito-temporal infarct. In subsequent months, the patient complained of fatigue, quadrantanopsia, memory problems, and topographical disorientation. The patient participated in multi-modality treatment, and in self-directed arts projects and physical activities. Six years later, she reported noticeable improvements in cognition and daily functioning, which were documented on neurocognitive testing. Comparison between initial and subsequent MRIs using FreeSurfer 5.3 identified neuroplastic brain changes in areas serving similar functions to the areas injured from the stroke. The case illustrates the neuropsychiatric presentation after right occipito-temporal stroke, the value of formal and self-directed cognitive rehabilitation, the extended time to cognitive recovery, and the ability of the brain to undergo neuroplastic changes.
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http://dx.doi.org/10.1016/j.cortex.2021.01.013DOI Listing
April 2021

Past, present and future role of retinal imaging in neurodegenerative disease.

Prog Retin Eye Res 2021 07 15;83:100938. Epub 2021 Jan 15.

Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.

Retinal imaging technology is rapidly advancing and can provide ever-increasing amounts of information about the structure, function and molecular composition of retinal tissue in humans in vivo. Most importantly, this information can be obtained rapidly, non-invasively and in many cases using Food and Drug Administration-approved devices that are commercially available. Technologies such as optical coherence tomography have dramatically changed our understanding of retinal disease and in many cases have significantly improved their clinical management. Since the retina is an extension of the brain and shares a common embryological origin with the central nervous system, there has also been intense interest in leveraging the expanding armamentarium of retinal imaging technology to understand, diagnose and monitor neurological diseases. This is particularly appealing because of the high spatial resolution, relatively low-cost and wide availability of retinal imaging modalities such as fundus photography or OCT compared to brain imaging modalities such as magnetic resonance imaging or positron emission tomography. The purpose of this article is to review and synthesize current research about retinal imaging in neurodegenerative disease by providing examples from the literature and elaborating on limitations, challenges and future directions. We begin by providing a general background of the most relevant retinal imaging modalities to ensure that the reader has a foundation on which to understand the clinical studies that are subsequently discussed. We then review the application and results of retinal imaging methodologies to several prevalent neurodegenerative diseases where extensive work has been done including sporadic late onset Alzheimer's Disease, Parkinson's Disease and Huntington's Disease. We also discuss Autosomal Dominant Alzheimer's Disease and cerebrovascular small vessel disease, where the application of retinal imaging holds promise but data is currently scarce. Although cerebrovascular disease is not generally considered a neurodegenerative process, it is both a confounder and contributor to neurodegenerative disease processes that requires more attention. Finally, we discuss ongoing efforts to overcome the limitations in the field and unmet clinical and scientific needs.
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http://dx.doi.org/10.1016/j.preteyeres.2020.100938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280255PMC
July 2021

Multicenter Validation of the max-ICH Score in Intracerebral Hemorrhage.

Ann Neurol 2021 03 21;89(3):474-484. Epub 2020 Dec 21.

Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.

Objective: Outcome prognostication unbiased by early care limitations (ECL) is essential for guiding treatment in patients presenting with intracerebral hemorrhage (ICH). The aim of this study was to determine whether the max-ICH (maximally treated ICH) Score provides improved and clinically useful prognostic estimation of functional long-term outcomes after ICH.

Methods: This multicenter validation study compared the prognostication of the max-ICH Score versus the ICH Score regarding diagnostic accuracy (discrimination and calibration) and clinical utility using decision curve analysis. We performed a joint investigation of individual participant data of consecutive spontaneous ICH patients (n = 4,677) from 2 retrospective German-wide studies (RETRACE I + II; anticoagulation-associated ICH only) conducted at 22 participating centers, one German prospective single-center study (UKER-ICH; nonanticoagulation-associated ICH only), and 1 US-based prospective longitudinal single-center study (MGH; both anticoagulation- and nonanticoagulation-associated ICH), treated between January 2006 and December 2015.

Results: Of 4,677 included ICH patients, 1,017 (21.7%) were affected by ECL (German cohort: 15.6% [440 of 2,377]; MGH: 31.0% [577 of 1,283]). Validation of long-term functional outcome prognostication by the max-ICH Score provided good and superior discrimination in patients without ECL compared with the ICH Score (area under the receiver operating curve [AUROC], German cohort: 0.81 [0.78-0.83] vs 0.74 [0.72-0.77], p < 0.01; MGH: 0.85 [0.81-0.89] vs 0.78 [0.74-0.82], p < 0.01), and for the entire cohort (AUROC, German cohort: 0.84 [0.82-0.86] vs 0.80 [0.77-0.82], p < 0.01; MGH: 0.83 [0.81-0.85] vs 0.77 [0.75-0.79], p < 0.01). Both scores showed no evidence of poor calibration. The clinical utility investigated by decision curve analysis showed, at high threshold probabilities (0.8, aiming to avoid false-positive poor outcome attribution), that the max-ICH Score provided a clinical net benefit compared with the ICH Score (14.1 vs 2.1 net predicted poor outcomes per 100 patients).

Interpretation: The max-ICH Score provides valid and improved prognostication of functional outcome after ICH. The associated clinical net benefit in minimizing false poor outcome attribution might potentially prevent unwarranted care limitations in patients with ICH. ANN NEUROL 2021;89:474-484.
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http://dx.doi.org/10.1002/ana.25969DOI Listing
March 2021

Association of Cerebral Small Vessel Disease and Cognitive Decline After Intracerebral Hemorrhage.

Neurology 2021 01 16;96(2):e182-e192. Epub 2020 Oct 16.

From U 1172-LilNCog-Lille Neuroscience and Cognition (M.P.), Université de Lille, Inserm, CHU Lille, France; Department of Neurology (M.P., L.S., L.X., A.C., T.P., S.S., C.K., K.S., S.M.G., C.D.A., M.E.G., J.R., A.V., A.B.), Hemorrhagic Stroke Research Program (L.S., A.C., S.M.G., C.D.A., M.E.G., J.R., A.V., A.B.), and Henry and Allison McCance Center for Brain Health (C.K., C.D.A., J.R., A.B.), Massachusetts General Hospital, Boston; Department of Neuroradiology (G.B.), Centre Hospitalier Sainte-Anne, Université Paris-Descartes, INSERM UMR 894, Paris, France; Department of Pharmacology, Faculty of Medicine (T.P.), Chulalongkorn University; and Chulalongkorn Stroke Center (T.P.), King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.

Objective: To determine whether MRI-based cerebral small vessel disease (CSVD) burden assessment, in addition to clinical and CT data, improved prediction of cognitive impairment after spontaneous intracerebral hemorrhage (ICH).

Methods: We analyzed data from ICH survivors enrolled in a single-center prospective study. We employed 3 validated CSVD burden scores: global, cerebral amyloid angiopathy (CAA)-specific, and hypertensive arteriopathy (HTNA)-specific. We quantified cognitive performance by administering the modified Telephone Interview for Cognitive Status test. We utilized linear mixed models to model cognitive decline rates, and survival models for new-onset dementia. We calculated CSVD scores' cutoffs to maximize predictive performance for dementia diagnosis.

Results: We enrolled 612 ICH survivors, and followed them for a median of 46.3 months (interquartile range 35.5-58.7). A total of 214/612 (35%) participants developed dementia. Higher global CSVD scores at baseline were associated with faster cognitive decline (coefficient -0.25, standard error [SE] 0.02) and dementia risk (sub-hazard ratio 1.35, 95% confidence interval 1.10-1.65). The global score outperformed the CAA and HTNA scores in predicting post-ICH dementia (all < 0.05). Compared to a model including readily available clinical and CT data, inclusion of the global CSVD score resulted in improved prediction of post-ICH dementia (area under the curve [AUC] 0.89, SE 0.02 vs AUC 0.81, SE 0.03, = 0.008 for comparison). Global CSVD scores ≥2 had highest sensitivity (83%) and specificity (91%) for dementia diagnosis.

Conclusions: A validated MRI-based CSVD score is associated with cognitive performance after ICH and improved diagnostic accuracy for predicting new onset of dementia.
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http://dx.doi.org/10.1212/WNL.0000000000011050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905779PMC
January 2021

genotype, hypertension severity and outcomes after intracerebral haemorrhage.

Brain Commun 2019 14;1(1):fcz018. Epub 2019 Sep 14.

Henry and Allison McCance Center for Brain Health, MGH, Boston, MA, USA.

Intracerebral haemorrhage in the elderly is a severe manifestation of common forms of cerebral small vessel disease. Nearly 60% of intracerebral haemorrhage survivors will develop clinical manifestations of small vessel disease progression including recurrent haemorrhage, ischaemic stroke, dementia, late-life depression and gait impairment within 5 years. Blood pressure measurements following intracerebral haemorrhage are strongly associated with this risk. However, aggressive blood pressure lowering in the elderly carries substantial risks. In order to determine whether there might be an opportunity to select individuals at the highest risk for small vessel disease progression for aggressive blood pressure reduction, we investigated whether gene variants ɛ2/ɛ4 modify the association between blood pressure and small vessel disease clinical progression after intracerebral haemorrhage. We conducted a single-centre longitudinal study at a tertiary care referral centre (Massachusetts General Hospital in Boston, MA, USA), analysing 716 consecutive survivors of acute intracerebral haemorrhage, enrolled from January 2006 to December 2016. We conducted research interviews at the time of enrolment and obtained genotypes from peripheral venous blood samples. We followed patients longitudinally by means of validated phone-based research encounters, aimed at gathering measurements of systolic and diastolic blood pressure, as well as information on small vessel disease clinical outcomes (including recurrent haemorrhage, incident ischaemic stroke, incident dementia, incident depression and incident gait impairment). ε4 and systolic blood pressure were associated with the risk of recurrent haemorrhage, ischaemic stroke and post-haemorrhage dementia, depression and gait impairment (all  < 0.05). and systolic blood pressure interacted to increase the risk of recurrent haemorrhage, ischaemic stroke, dementia and gait impairment (all interaction  < 0.05). Among patients with elevated blood pressure following intracerebral haemorrhage (average systolic blood pressure 120-129 mmHg and diastolic blood pressure <80 mmHg) only those with one or more ε4 copies were at increased risk for one or more small vessel disease outcomes (hazard ratio = 1.97, 95% confidence interval 1.17-3.31). Among haemorrhage survivors with hypertension (stage 1 and beyond) genotype also stratified risk for all small vessel disease outcomes. In conclusion, genotype modifies the already strong association of hypertension with multiple small vessel disease clinical outcomes among intracerebral haemorrhage survivors. These data raise the possibility that genetic screening could inform blood pressure treatment goals in this patient population.
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http://dx.doi.org/10.1093/braincomms/fcz018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425529PMC
September 2019

Telemedicine in Behavioral Neurology-Neuropsychiatry: Opportunities and Challenges Catalyzed by COVID-19.

Cogn Behav Neurol 2020 09;33(3):226-229

Cognitive Behavioral Neurology Unit, Department of Neurology.

Coronavirus 2019 (COVID-19) has profoundly impacted the well-being of society and the practice of medicine across health care systems worldwide. As with many other subspecialties, the clinical paradigm in behavioral neurology and neuropsychiatry (BN-NP) was transformed abruptly, transitioning to real-time telemedicine for the assessment and management of the vast majorities of patient populations served by our subspecialty. In this commentary, we outline themes from the BN-NP perspective that reflect the emerging lessons we learned using telemedicine during the COVID-19 pandemic. Positive developments include the ability to extend consultations and management to patients in our high-demand field, maintenance of continuity of care, enhanced ecological validity, greater access to a variety of well-reimbursed telemedicine options (telephone and video) that help bridge the digital divide, and educational and research opportunities. Challenges include the need to adapt the mental state examination to the telemedicine environment, the ability to perform detailed motor neurologic examinations in patients where motor features are important diagnostic considerations, appreciating nonverbal cues, managing acute safety and behavioral concerns in less controlled environments, and navigating intervention-based (neuromodulation) clinics requiring in-person contact. We hope that our reflections help to catalyze discussions that should take place within the Society for Behavioral and Cognitive Neurology, the American Neuropsychiatric Association, and allied organizations regarding how to optimize real-time telemedicine practices for our subspecialty now and into the future.
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http://dx.doi.org/10.1097/WNN.0000000000000239DOI Listing
September 2020

Association of Selective Serotonin Reuptake Inhibitor Use After Intracerebral Hemorrhage With Hemorrhage Recurrence and Depression Severity.

JAMA Neurol 2020 Aug 31. Epub 2020 Aug 31.

Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center, Boston, Massachusetts.

Importance: Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat poststroke depression but are associated with increased incidence of first-ever intracerebral hemorrhage (ICH) in the general population. The decision to treat ICH survivors with SSRIs must therefore balance potential risks of ICH recurrence with presumed benefits on depressive symptoms.

Objective: To determine whether SSRI use among survivors of primary ICH was associated with ICH recurrence and decreased severity of depressive symptoms.

Design, Setting, And Participants: Longitudinal ICH cohort study at a tertiary care center enrolling from January 2006 to December 2017, with follow-up for a median of 53.2 months (interquartile range, 42.3-61.2 months). The study included 1279 consenting individuals (1049 White, 89 Black, 77 Hispanic, and 64 other race/ethnicity) of 1335 eligible patients presenting with primary ICH and who were discharged alive from initial hospitalization for stroke.

Main Outcomes And Measures: We conducted univariable and multivariable analyses for ICH recurrence risk and depression severity, including subset analyses for patients with 1 or more of the following characteristics associated with high ICH recurrence risk: (1) lobar ICH; (2) presence of the apolipoprotein ε2/ε4 gene variants; (3) prior history of ICH/TIA/ischemic stroke; and (4) Black or Hispanic race/ethnicity.

Results: Mean age of study participants was 71.3 years, with 602 women (47%); of the 1279 participants, 1049 were White, 89 were Black, 77 were Hispanic, and 64 were other race/ethnicity. SSRI exposure was associated with both ICH recurrence (subhazard ratio [SHR], 1.31; 95% CI, 1.08-1.59) and resolution of post-ICH depression (SHR, 1.53; 95% CI, 1.12 2.09). Among those individuals at high risk for recurrent ICH, SSRIs were associated with further elevation in risk for ICH recurrence (SHR, 1.79; 95% CI, 1.22-2.64) compared with all other survivors of ICH (SHR, 1.20; 95% CI, 1.01-1.42; P = .008 for comparison of effect sizes). The association of SSRI with reduced depressive symptoms did not differ between high those at high risk for recurrent ICH and all other ICH survivors.

Conclusions And Relevance: Selective serotonin reuptake inhibitor exposure after ICH is associated with both improvement in depressive symptoms and increased risk of recurrent hemorrhagic stroke. Clinical history, neuroimaging data, and genetic biomarkers may help to identify survivors of ICH more likely to safely tolerate SSRI use.
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http://dx.doi.org/10.1001/jamaneurol.2020.3142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489430PMC
August 2020

Recommendations for Cardiovascular Prevention During the Sars-Cov-2 Pandemic: An Executive Document by the Board of the Italian Society of Cardiovascular Prevention.

High Blood Press Cardiovasc Prev 2020 Oct 30;27(5):373-377. Epub 2020 Jul 30.

Università degli studi di Padova, Padua, Italy.

In 2020, the Sars-Cov-2 pandemic is causing a huge and dramatic impact on healthcare systems worldwide. During this emergency, fragile patients suffering from other comorbidities, especially patients susceptible to or affected by cardiovascular disease, are the ones most exposed to the poorer outcomes. Therefore, it is still mandatory to continue to strictly adhere to the rules of cardiovascular prevention. This document aims to provide all doctors with simple and clear recommendations in order to spread useful messages to the widest number of subjects in order to continue the battle against cardiovascular diseases even in times of pandemic.
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http://dx.doi.org/10.1007/s40292-020-00401-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391228PMC
October 2020

A Pooled Analysis of Diffusion-Weighted Imaging Lesions in Patients With Acute Intracerebral Hemorrhage.

JAMA Neurol 2020 11;77(11):1390-1397

Division of Neurosciences Critical Care, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Importance: The etiology and significance of diffusion-weighted imaging (DWI) lesions in patients with acute intracerebral hemorrhage (ICH) remain unclear.

Objective: To evaluate which factors are associated with DWI lesions, whether associated factors differ by ICH location, and whether DWI lesions are associated with functional outcomes.

Design, Setting, And Participants: This analysis pooled individual patient data from 3 randomized clinical trials (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3 trial, Antihypertensive Treatment of Acute Cerebral Hemorrhage trial, and Intracerebral Hemorrhage Deferoxamine phase 2 trial) and 1 multicenter prospective study (Ethnic/Racial Variations of Intracerebral Hemorrhage). Patients were enrolled from August 1, 2010, to September 30, 2018. Of the 4782 patients, 1788 who underwent magnetic resonance imaging scans of the brain were included. Data were analyzed from July 1 to December 31, 2019.

Main Outcomes And Measures: The primary outcome consisted of factors associated with DWI lesions. Secondary outcomes were poor functional outcome, defined as a modified Rankin score (mRS) of 4 to 6, and mortality, both assessed at 3 months. Mixed-effects logistic regression was used to evaluate the association between exposures and outcomes. Subgroup analyses stratified by hematoma location were performed.

Results: After exclusion of 36 patients with missing data on DWI lesions, 1752 patients were included in the analysis (1019 men [58.2%]; mean [SD] age, 60.8 [13.3] years). Diffusion-weighted imaging lesions occurred in 549 patients (31.3%). In mixed-effects regression models, factors associated with DWI lesions included younger age (odds ratio [OR] per year, 0.98; 95% CI, 0.97-0.99), black race (OR, 1.64; 95% CI, 1.17-2.30), admission systolic blood pressure (OR per 10-mm Hg increase, 1.13; 95% CI, 1.08-1.18), baseline hematoma volume (OR per 10-mL increase, 1.12; 95% CI, 1.02-1.22), cerebral microbleeds (OR, 1.85; 95% CI, 1.39-2.46), and leukoaraiosis (OR, 1.59; 95% CI, 1.67-2.17). Diffusion-weighted imaging lesions were independently associated with poor mRS (OR, 1.50; 95% CI, 1.13-2.00), but not with mortality (OR, 1.11; 95% CI, 0.72-1.71). In subgroup analyses, similar factors were associated with DWI lesions in lobar and deep ICH. Diffusion-weighted imaging lesions were associated with poor mRS in deep but not lobar ICH.

Conclusions And Relevance: In a large, heterogeneous cohort of prospectively identified patients with ICH, results were consistent with the hypothesis that DWI lesions represent acute sequelae of chronic cerebral small vessel disease, particularly hypertensive vasculopathy. Diffusion-weighted imaging lesions portend a worse prognosis after ICH, mainly deep hemorrhages.
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http://dx.doi.org/10.1001/jamaneurol.2020.2349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372494PMC
November 2020

Combining Imaging and Genetics to Predict Recurrence of Anticoagulation-Associated Intracerebral Hemorrhage.

Stroke 2020 07 10;51(7):2153-2160. Epub 2020 Jun 10.

Department of Neurology (A.B., S.U., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A., J.R.), Massachusetts General Hospital, Boston.

Background And Purpose: For survivors of oral anticoagulation therapy (OAT)-associated intracerebral hemorrhage (OAT-ICH) who are at high risk for thromboembolism, the benefits of OAT resumption must be weighed against increased risk of recurrent hemorrhagic stroke. The ε2/ε4 alleles of the () gene, MRI-defined cortical superficial siderosis, and cerebral microbleeds are the most potent risk factors for recurrent ICH. We sought to determine whether combining MRI markers and genotype could have clinical impact by identifying ICH survivors in whom the risks of OAT resumption are highest.

Methods: Joint analysis of data from 2 longitudinal cohort studies of OAT-ICH survivors: (1) MGH-ICH study (Massachusetts General Hospital ICH) and (2) longitudinal component of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage). We evaluated whether MRI markers and genotype predict ICH recurrence. We then developed and validated a combined -MRI classification scheme to predict ICH recurrence, using Classification and Regression Tree analysis.

Results: Cortical superficial siderosis, cerebral microbleed, and ε2/ε4 variants were independently associated with ICH recurrence after OAT-ICH (all <0.05). Combining genotype and MRI data resulted in improved prediction of ICH recurrence (Harrell C: 0.79 versus 0.55 for clinical data alone, =0.033). In the MGH (training) data set, CSS, cerebral microbleed, and ε2/ε4 stratified likelihood of ICH recurrence into high-, medium-, and low-risk categories. In the ERICH (validation) data set, yearly ICH recurrence rates for high-, medium-, and low-risk individuals were 6.6%, 2.5%, and 0.9%, respectively, with overall area under the curve of 0.91 for prediction of recurrent ICH.

Conclusions: Combining MRI and genotype stratifies likelihood of ICH recurrence into high, medium, and low risk. If confirmed in prospective studies, this combined -MRI classification scheme may prove useful for selecting individuals for OAT resumption after ICH.
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http://dx.doi.org/10.1161/STROKEAHA.120.028310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311289PMC
July 2020

Genetically Elevated LDL Associates with Lower Risk of Intracerebral Hemorrhage.

Ann Neurol 2020 07 7;88(1):56-66. Epub 2020 May 7.

Medical Research Council Population Health Research Unit, University of Oxford, Oxford, UK.

Objective: Observational studies point to an inverse correlation between low-density lipoprotein (LDL) cholesterol levels and risk of intracerebral hemorrhage (ICH), but it remains unclear whether this association is causal. We tested the hypothesis that genetically elevated LDL is associated with reduced risk of ICH.

Methods: We constructed one polygenic risk score (PRS) per lipid trait (total cholesterol, LDL, high-density lipoprotein [HDL], and triglycerides) using independent genomewide significant single nucleotide polymorphisms (SNPs) for each trait. We used data from 316,428 individuals enrolled in the UK Biobank to estimate the effect of each PRS on its corresponding trait, and data from 1,286 ICH cases and 1,261 matched controls to estimate the effect of each PRS on ICH risk. We used these estimates to conduct Mendelian Randomization (MR) analyses.

Results: We identified 410, 339, 393, and 317 lipid-related SNPs for total cholesterol, LDL, HDL, and triglycerides, respectively. All four PRSs were strongly associated with their corresponding trait (all p < 1.00 × 10 ). While one SD increase in the PRSs for total cholesterol (odds ratio [OR] = 0.92; 95% confidence interval [CI] = 0.85-0.99; p = 0.03) and LDL cholesterol (OR = 0.88; 95% CI = 0.81-0.95; p = 0.002) were inversely associated with ICH risk, no significant associations were found for HDL and triglycerides (both p > 0.05). MR analyses indicated that 1mmol/L (38.67mg/dL) increase of genetically instrumented total and LDL cholesterol were associated with 23% (OR = 0.77; 95% CI = 0.65-0.98; p = 0.03) and 41% lower risks of ICH (OR = 0.59; 95% CI = 0.42-0.82; p = 0.002), respectively.

Interpretation: Genetically elevated LDL levels were associated with lower risk of ICH, providing support for a potential causal role of LDL cholesterol in ICH. ANN NEUROL 2020 ANN NEUROL 2020;88:56-66.
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http://dx.doi.org/10.1002/ana.25740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523882PMC
July 2020

Non-Traumatic Subdural Hemorrhage and Risk of Arterial Ischemic Events.

Stroke 2020 05 17;51(5):1464-1469. Epub 2020 Mar 17.

From the Clinical and Translational Neuroscience Unit, Department of Neurology, Feil Family Brain and Mind Research Institute (S.B.M., M.P., N.S.P., C.I., A.E.M., J.C., B.B.N., H.K.), Weill Cornell Medicine, New York, NY.

Background and Purpose- The risk of arterial ischemic events after subdural hemorrhage (SDH) is poorly understood. This study aimed to evaluate the risk of acute ischemic stroke and myocardial infarction among patients with and without nontraumatic SDH. Methods- We performed a retrospective cohort study using claims data from 2008 through 2014 from a nationally representative sample of Medicare beneficiaries. The exposure was nontraumatic SDH. Our primary outcome was an arterial ischemic event, a composite of acute ischemic stroke and acute myocardial infarction. Secondary outcomes were ischemic stroke alone and myocardial infarction alone. We used validated , , diagnosis codes to identify our predictor and outcomes. Using Cox regression and corresponding survival probabilities, adjusted for demographics and vascular comorbidities, we computed the hazard ratio in 4-week intervals after SDH discharge. We performed secondary analyses stratified by strong indications for antithrombotic therapy (composite of atrial fibrillation, peripheral vascular disease, valvular heart disease, and venous thromboembolism). Results- Among 1.7 million Medicare beneficiaries, 2939 were diagnosed with SDH. In the 4 weeks after SDH, patients' risk of an arterial ischemic event was substantially increased (hazard ratio, 3.6 [95% CI, 1.9-5.5]). There was no association between SDH diagnosis and arterial ischemic events beyond 4 weeks. In secondary analysis, during the 4 weeks after SDH, patients' risk of ischemic stroke was increased (hazard ratio, 4.2 [95% CI, 2.1-7.3]) but their risk of myocardial infarction was not (hazard ratio, 0.8 [95% CI, 0.2-1.7]). Patients with strong indications for antithrombotic therapy had increased risks for arterial ischemic events similar to patients in the primary analysis, but those without such indications did not demonstrate an increased risk for arterial ischemic events. Conclusions- Among Medicare beneficiaries, we found a heightened risk of arterial ischemic events driven by an increased risk of ischemic stroke, in the 4 weeks after nontraumatic SDH. This increased risk may be due to interruption of antithrombotic therapy after SDH diagnosis.
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http://dx.doi.org/10.1161/STROKEAHA.119.028510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188584PMC
May 2020

Antiplatelet Therapy After Spontaneous Intracerebral Hemorrhage and Functional Outcomes.

Stroke 2019 11 20;50(11):3057-3063. Epub 2019 Sep 20.

Henry and Allison McCance Center for Brain Health (A.B., J.R.), Massachusetts General Hospital, Boston, MA.

Background and Purpose- Observational data suggest that antiplatelet therapy after intracerebral hemorrhage (ICH) alleviates thromboembolic risk without increasing the risk of recurrent ICH. Given the paucity of data on the relationship between antiplatelet therapy after ICH and functional outcomes, we aimed to study this association in a multicenter cohort. Methods- We meta-analyzed data from (1) the Massachusetts General Hospital ICH registry (n=1854), (2) the Virtual International Stroke Trials Archive database (n=762), and (3) the Yale stroke registry (n=185). Our exposure was antiplatelet therapy after ICH, which was modeled as a time-varying covariate. Our primary outcomes were all-cause mortality and a composite of major disability or death (modified Rankin Scale score 4-6). We used Cox proportional regression analyses to estimate the hazard ratio of death or poor functional outcome as a function of antiplatelet therapy and random-effects meta-analysis to pool the estimated HRs across studies. Additional analyses stratified by hematoma location (lobar and deep ICH) were performed. Results- We included a total of 2801 ICH patients, of whom 288 (10.3%) were started on antiplatelet medications after ICH. Median times to antiplatelet therapy ranged from 7 to 39 days. Antiplatelet therapy after ICH was not associated with mortality (hazard ratio, 0.85; 95% CI, 0.66-1.09), or death or major disability (hazard ratio, 0.83; 95% CI, 0.59-1.16) compared with patients not started on antiplatelet therapy. Similar results were obtained in additional analyses stratified by hematoma location. Conclusions- Antiplatelet therapy after ICH appeared safe and was not associated with all-cause mortality or functional outcome, regardless of hematoma location. Randomized clinical trials are needed to determine the effects and harms of antiplatelet therapy after ICH.
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http://dx.doi.org/10.1161/STROKEAHA.119.025972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941441PMC
November 2019
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