Andreas Charidimou1, Gregoire Boulouis1, Duangnapa Roongpiboonsopit1, Eitan Auriel1, Marco Pasi1, Kellen Haley1, Ellis S van Etten1, Sergi Martinez-Ramirez1, Alison Ayres1, Anastasia Vashkevich1, Kristin M Schwab1, Joshua N Goldstein1, Jonathan Rosand1, Anand Viswanathan1, Steven M Greenberg1, M Edip Gurol2. 1. From the Hemorrhagic Stroke Research Program, Department of Neurology, Stroke Research Center (A.C., G.B., D.R., E.A., M.P., K.H., E.S.v.E., S.M.-R., A.A., A. Vashkevich, K.M.S., J.N.G., J.R., A. Viswanathan, S.M.G., M.E.G.), and Division of Neurocritical Care and Emergency Neurology (J.N.G., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston; and Department of Neurology (E.A.), Carmel Medical Center, Haifa, Israel. 2. From the Hemorrhagic Stroke Research Program, Department of Neurology, Stroke Research Center (A.C., G.B., D.R., E.A., M.P., K.H., E.S.v.E., S.M.-R., A.A., A. Vashkevich, K.M.S., J.N.G., J.R., A. Viswanathan, S.M.G., M.E.G.), and Division of Neurocritical Care and Emergency Neurology (J.N.G., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston; and Department of Neurology (E.A.), Carmel Medical Center, Haifa, Israel. edip@mail.harvard.edu.
Abstract
OBJECTIVE: In order to explore the mechanisms of cortical superficial siderosis (cSS) multifocality and its clinical implications for recurrent intracerebral hemorrhage (ICH) risk in patients with cerebral amyloid angiopathy (CAA), we used a new rating method that we developed specifically to evaluate cSS extent at spatially separated foci. METHODS: Consecutive patients with CAA-related ICH according to Boston criteria from a single-center prospective cohort were analyzed. The new score that assesses cSS multifocality (total range 0-4) showed excellent interrater reliability (k = 0.87). The association of cSS with markers of CAA and acute ICH was investigated. Patients were followed prospectively for recurrent symptomatic ICH. RESULTS: The cohort included 313 patients with CAA. Multifocal cSS prevalence was 21.1%. APOE ε2 allele prevalence was higher in patients with multifocal cSS. In probable/definite CAA, cSS multifocality was independently associated with neuroimaging markers of CAA severity, including lobar microbleeds, but not with acute ICH features, which conversely, were determinants of cSS in possible CAA. During a median follow-up of 2.6 years (interquartile range 0.9-5.1 years), the annual ICH recurrence rates per cSS scores (0-4) were 5%, 6.5%, 13.5%, 16.2%, and 26.9%, respectively. cSS multifocality (presence and spread) was the only independent predictor of increased symptomatic ICH risk (hazard ratio 3.19; 95% confidence interval 1.77-5.75; p < 0.0001). CONCLUSIONS: The multifocality of cSS correlates with disease severity in probable CAA; therefore cSS is likely to be caused by discrete hemorrhagic foci. The new cSS scoring system might be valuable for clinicians in determining annual risk of ICH recurrence.
OBJECTIVE: In order to explore the mechanisms of cortical superficial siderosis (cSS) multifocality and its clinical implications for recurrent intracerebral hemorrhage (ICH) risk in patients with cerebral amyloid angiopathy (CAA), we used a new rating method that we developed specifically to evaluate cSS extent at spatially separated foci. METHODS: Consecutive patients with CAA-related ICH according to Boston criteria from a single-center prospective cohort were analyzed. The new score that assesses cSS multifocality (total range 0-4) showed excellent interrater reliability (k = 0.87). The association of cSS with markers of CAA and acute ICH was investigated. Patients were followed prospectively for recurrent symptomatic ICH. RESULTS: The cohort included 313 patients with CAA. Multifocal cSS prevalence was 21.1%. APOE ε2 allele prevalence was higher in patients with multifocal cSS. In probable/definite CAA, cSS multifocality was independently associated with neuroimaging markers of CAA severity, including lobar microbleeds, but not with acute ICH features, which conversely, were determinants of cSS in possible CAA. During a median follow-up of 2.6 years (interquartile range 0.9-5.1 years), the annual ICH recurrence rates per cSS scores (0-4) were 5%, 6.5%, 13.5%, 16.2%, and 26.9%, respectively. cSS multifocality (presence and spread) was the only independent predictor of increased symptomatic ICH risk (hazard ratio 3.19; 95% confidence interval 1.77-5.75; p < 0.0001). CONCLUSIONS: The multifocality of cSS correlates with disease severity in probable CAA; therefore cSS is likely to be caused by discrete hemorrhagic foci. The new cSS scoring system might be valuable for clinicians in determining annual risk of ICH recurrence.
Authors: Jun Ni; Eitan Auriel; Jenelle Jindal; Alison Ayres; Kristin M Schwab; Sergi Martinez-Ramirez; Edip M Gurol; Steven M Greenberg; Anand Viswanathan Journal: Cerebrovasc Dis Date: 2015-04-08 Impact factor: 2.762
Authors: S M Greenberg; J P Vonsattel; A Z Segal; R I Chiu; A E Clatworthy; A Liao; B T Hyman; G W Rebeck Journal: Neurology Date: 1998-04 Impact factor: 9.910
Authors: M E Gurol; M C Irizarry; E E Smith; S Raju; R Diaz-Arrastia; T Bottiglieri; J Rosand; J H Growdon; S M Greenberg Journal: Neurology Date: 2006-01-10 Impact factor: 9.910
Authors: Andreas Charidimou; Zane Jaunmuktane; Jean-Claude Baron; Matthew Burnell; Pascale Varlet; Andre Peeters; John Xuereb; Rolf Jäger; Sebastian Brandner; David J Werring Journal: Neurology Date: 2013-11-27 Impact factor: 9.910
Authors: Duangnapa Roongpiboonsopit; Andreas Charidimou; Christopher M William; Arne Lauer; Guido J Falcone; Sergi Martinez-Ramirez; Alessandro Biffi; Alison Ayres; Anastasia Vashkevich; Oluwole O Awosika; Jonathan Rosand; M Edip Gurol; Scott B Silverman; Steven M Greenberg; Anand Viswanathan Journal: Neurology Date: 2016-09-30 Impact factor: 9.910
Authors: Carolyn Akers; Lealani May Y Acosta; Ciaran Considine; Daniel Claassen; Howard Kirshner; Matthew Schrag Journal: Curr Neurol Neurosci Rep Date: 2019-07-27 Impact factor: 5.081
Authors: Marco Pasi; Thanakit Pongpitakmetha; Andreas Charidimou; Sanjula D Singh; Hsin-Hsi Tsai; Li Xiong; Gregoire Boulouis; Andrew D Warren; Jonathan Rosand; Matthew P Frosch; Anand Viswanathan; M Edip Gurol; Steven M Greenberg Journal: Stroke Date: 2019-06-04 Impact factor: 7.914
Authors: Alvin S Das; Elif Gökçal; Robert W Regenhardt; Andrew D Warren; Alessandro Biffi; Joshua N Goldstein; W Taylor Kimberly; Anand Viswanathan; Lee H Schwamm; Jonathan Rosand; Steven M Greenberg; M Edip Gurol Journal: J Neurol Date: 2022-08-23 Impact factor: 6.682
Authors: Thanakit Pongpitakmetha; Panagiotis Fotiadis; Marco Pasi; Gregoire Boulouis; Li Xiong; Andrew D Warren; Kristin M Schwab; Jonathan Rosand; M Edip Gurol; Steven M Greenberg; Anand Viswanathan; Andreas Charidimou Journal: Neurology Date: 2020-04-13 Impact factor: 9.910
Authors: Andreas Charidimou; Hazel I Zonneveld; Sara Shams; Kejal Kantarci; Ashkan Shoamanesh; Saima Hilal; Paul A Yates; Gregoire Boulouis; Han Kyu Na; Marco Pasi; Allesandro Biffi; Yuek Ling Chai; Joyce Ruifen Chong; Lars-Olof Wahlund; Jack R Clifford; Christopher Chen; M Edip Gurol; Joshua N Goldstein; Duk L Na; Frederik Barkhof; Sang Won Seo; Jonathan Rosand; Steven M Greenberg; Anand Viswanathan Journal: Neurology Date: 2019-06-26 Impact factor: 9.910
Authors: Juan Pablo Castello; Marco Pasi; Jessica R Abramson; Axana Rodriguez-Torres; Sandro Marini; Stacie Demel; Lee Gilkerson; Patryk Kubiszewski; Andreas Charidimou; Christina Kourkoulis; Zora DiPucchio; Kristin Schwab; M Edip Gurol; Anand Viswanathan; Christopher D Anderson; Carl D Langefeld; Matthew L Flaherty; Amytis Towfighi; Steven M Greenberg; Daniel Woo; Jonathan Rosand; Alessandro Biffi Journal: Neurology Date: 2021-04-21 Impact factor: 9.910
Authors: Nicolas Raposo; Andreas Charidimou; Duangnapa Roongpiboonsopit; Michelle Onyekaba; M Edip Gurol; Jonathan Rosand; Steven M Greenberg; Joshua N Goldstein; Anand Viswanathan Journal: Neurology Date: 2020-02-04 Impact factor: 11.800
Authors: Qi Li; Maria Clara Zanon Zotin; Andrew D Warren; Yuan Ma; Edip Gurol; Joshua N Goldstein; Steven M Greenberg; Andreas Charidimou; Nicolas Raposo; Anand Viswanathan Journal: Neurology Date: 2020-10-21 Impact factor: 9.910