Cortical superficial siderosis predicts early recurrent lobar hemorrhage.
OBJECTIVE
To identify predictors of early lobar intracerebral hemorrhage (ICH) recurrence, defined as a new ICH within 6 months of the index event, in patients with cerebral amyloid angiopathy (CAA).


METHODS
Participants were consecutive survivors (age ≥55 years) of spontaneous symptomatic probable or possible CAA-related lobar ICH according to the Boston criteria, drawn from an ongoing single-center cohort study. Neuroimaging markers ascertained in CT or MRI included focal (≤3 sulci) or disseminated (>3 sulci) cortical superficial siderosis (cSS), acute convexity subarachnoid hemorrhage (cSAH), cerebral microbleeds, white matter hyperintensities burden and location, and baseline ICH volume. Participants were followed prospectively for recurrent symptomatic ICH. Cox proportional hazards models were used to identify predictors of early recurrent ICH adjusting for potential confounders.


RESULTS
A total of 292 patients were enrolled. Twenty-one patients (7%) had early recurrent ICH. Of these, 24% had disseminated cSS on MRI and 19% had cSAH on CT scan. In univariable analysis, the presence of disseminated cSS, cSAH, and history of previous ICH were predictors of early recurrent ICH (p < 0.05 for all comparisons). After adjusting for age and history of previous ICH, disseminated cSS on MRI and cSAH on CT were independent predictors of early recurrent ICH (hazard ratio [HR] 3.92, 95% confidence interval [CI] 1.38-11.17, p = 0.011, and HR 3.48, 95% CI 1.13-10.73, p = 0.030, respectively).


CONCLUSIONS
Disseminated cSS on MRI and cSAH on CT are independent imaging markers of increased risk for early recurrent ICH. These markers may provide additional insights into the mechanisms of ICH recurrence in patients with CAA.
From The Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center (D.R., A.C., A.L., G.J.F., S.M.-R., A.A., A. Vashkevich, M.E.G., S.B.S., S.M.G., A. Viswanathan), and Division of Behavioral Neurology (A.B.), Department of Neurology, Division of Neuropsychiatry, Department of Psychiatry (A.B.), Neuropathology Service, Department of Pathology (C.M.W.), and The Center for Human Genetic Research (G.J.F., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and Human Cortical Physiology and Stroke Neurorehabilitation Section (O.O.A.), NINDS/NIH, Bethesda, MD. duangnapar@nu.ac.th.
Duangnapa
D
Roongpiboonsopit
From The Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center (D.R., A.C., A.L., G.J.F., S.M.-R., A.A., A. Vashkevich, M.E.G., S.B.S., S.M.G., A. Viswanathan), and Division of Behavioral Neurology (A.B.), Department of Neurology, Division of Neuropsychiatry, Department of Psychiatry (A.B.), Neuropathology Service, Department of Pathology (C.M.W.), and The Center for Human Genetic Research (G.J.F., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and Human Cortical Physiology and Stroke Neurorehabilitation Section (O.O.A.), NINDS/NIH, Bethesda, MD.
Andreas
A
Charidimou
From The Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center (D.R., A.C., A.L., G.J.F., S.M.-R., A.A., A. Vashkevich, M.E.G., S.B.S., S.M.G., A. Viswanathan), and Division of Behavioral Neurology (A.B.), Department of Neurology, Division of Neuropsychiatry, Department of Psychiatry (A.B.), Neuropathology Service, Department of Pathology (C.M.W.), and The Center for Human Genetic Research (G.J.F., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and Human Cortical Physiology and Stroke Neurorehabilitation Section (O.O.A.), NINDS/NIH, Bethesda, MD.
Christopher M
CM
William
From The Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center (D.R., A.C., A.L., G.J.F., S.M.-R., A.A., A. Vashkevich, M.E.G., S.B.S., S.M.G., A. Viswanathan), and Division of Behavioral Neurology (A.B.), Department of Neurology, Division of Neuropsychiatry, Department of Psychiatry (A.B.), Neuropathology Service, Department of Pathology (C.M.W.), and The Center for Human Genetic Research (G.J.F., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and Human Cortical Physiology and Stroke Neurorehabilitation Section (O.O.A.), NINDS/NIH, Bethesda, MD.
Arne
A
Lauer
From The Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center (D.R., A.C., A.L., G.J.F., S.M.-R., A.A., A. Vashkevich, M.E.G., S.B.S., S.M.G., A. Viswanathan), and Division of Behavioral Neurology (A.B.), Department of Neurology, Division of Neuropsychiatry, Department of Psychiatry (A.B.), Neuropathology Service, Department of Pathology (C.M.W.), and The Center for Human Genetic Research (G.J.F., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and Human Cortical Physiology and Stroke Neurorehabilitation Section (O.O.A.), NINDS/NIH, Bethesda, MD.
Guido J
GJ
Falcone
From The Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center (D.R., A.C., A.L., G.J.F., S.M.-R., A.A., A. Vashkevich, M.E.G., S.B.S., S.M.G., A. Viswanathan), and Division of Behavioral Neurology (A.B.), Department of Neurology, Division of Neuropsychiatry, Department of Psychiatry (A.B.), Neuropathology Service, Department of Pathology (C.M.W.), and The Center for Human Genetic Research (G.J.F., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and Human Cortical Physiology and Stroke Neurorehabilitation Section (O.O.A.), NINDS/NIH, Bethesda, MD.
Sergi
S
Martinez-Ramirez
From The Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center (D.R., A.C., A.L., G.J.F., S.M.-R., A.A., A. Vashkevich, M.E.G., S.B.S., S.M.G., A. Viswanathan), and Division of Behavioral Neurology (A.B.), Department of Neurology, Division of Neuropsychiatry, Department of Psychiatry (A.B.), Neuropathology Service, Department of Pathology (C.M.W.), and The Center for Human Genetic Research (G.J.F., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and Human Cortical Physiology and Stroke Neurorehabilitation Section (O.O.A.), NINDS/NIH, Bethesda, MD.
Alessandro
A
Biffi
From The Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center (D.R., A.C., A.L., G.J.F., S.M.-R., A.A., A. Vashkevich, M.E.G., S.B.S., S.M.G., A. Viswanathan), and Division of Behavioral Neurology (A.B.), Department of Neurology, Division of Neuropsychiatry, Department of Psychiatry (A.B.), Neuropathology Service, Department of Pathology (C.M.W.), and The Center for Human Genetic Research (G.J.F., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and Human Cortical Physiology and Stroke Neurorehabilitation Section (O.O.A.), NINDS/NIH, Bethesda, MD.
Alison
A
Ayres
From The Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center (D.R., A.C., A.L., G.J.F., S.M.-R., A.A., A. Vashkevich, M.E.G., S.B.S., S.M.G., A. Viswanathan), and Division of Behavioral Neurology (A.B.), Department of Neurology, Division of Neuropsychiatry, Department of Psychiatry (A.B.), Neuropathology Service, Department of Pathology (C.M.W.), and The Center for Human Genetic Research (G.J.F., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and Human Cortical Physiology and Stroke Neurorehabilitation Section (O.O.A.), NINDS/NIH, Bethesda, MD.
Anastasia
A
Vashkevich
From The Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center (D.R., A.C., A.L., G.J.F., S.M.-R., A.A., A. Vashkevich, M.E.G., S.B.S., S.M.G., A. Viswanathan), and Division of Behavioral Neurology (A.B.), Department of Neurology, Division of Neuropsychiatry, Department of Psychiatry (A.B.), Neuropathology Service, Department of Pathology (C.M.W.), and The Center for Human Genetic Research (G.J.F., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and Human Cortical Physiology and Stroke Neurorehabilitation Section (O.O.A.), NINDS/NIH, Bethesda, MD.
Oluwole O
OO
Awosika
From The Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center (D.R., A.C., A.L., G.J.F., S.M.-R., A.A., A. Vashkevich, M.E.G., S.B.S., S.M.G., A. Viswanathan), and Division of Behavioral Neurology (A.B.), Department of Neurology, Division of Neuropsychiatry, Department of Psychiatry (A.B.), Neuropathology Service, Department of Pathology (C.M.W.), and The Center for Human Genetic Research (G.J.F., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and Human Cortical Physiology and Stroke Neurorehabilitation Section (O.O.A.), NINDS/NIH, Bethesda, MD.
Jonathan
J
Rosand
From The Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center (D.R., A.C., A.L., G.J.F., S.M.-R., A.A., A. Vashkevich, M.E.G., S.B.S., S.M.G., A. Viswanathan), and Division of Behavioral Neurology (A.B.), Department of Neurology, Division of Neuropsychiatry, Department of Psychiatry (A.B.), Neuropathology Service, Department of Pathology (C.M.W.), and The Center for Human Genetic Research (G.J.F., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and Human Cortical Physiology and Stroke Neurorehabilitation Section (O.O.A.), NINDS/NIH, Bethesda, MD.
M Edip
ME
Gurol
From The Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center (D.R., A.C., A.L., G.J.F., S.M.-R., A.A., A. Vashkevich, M.E.G., S.B.S., S.M.G., A. Viswanathan), and Division of Behavioral Neurology (A.B.), Department of Neurology, Division of Neuropsychiatry, Department of Psychiatry (A.B.), Neuropathology Service, Department of Pathology (C.M.W.), and The Center for Human Genetic Research (G.J.F., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and Human Cortical Physiology and Stroke Neurorehabilitation Section (O.O.A.), NINDS/NIH, Bethesda, MD.
Scott B
SB
Silverman
From The Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center (D.R., A.C., A.L., G.J.F., S.M.-R., A.A., A. Vashkevich, M.E.G., S.B.S., S.M.G., A. Viswanathan), and Division of Behavioral Neurology (A.B.), Department of Neurology, Division of Neuropsychiatry, Department of Psychiatry (A.B.), Neuropathology Service, Department of Pathology (C.M.W.), and The Center for Human Genetic Research (G.J.F., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and Human Cortical Physiology and Stroke Neurorehabilitation Section (O.O.A.), NINDS/NIH, Bethesda, MD.
Steven M
SM
Greenberg
From The Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center (D.R., A.C., A.L., G.J.F., S.M.-R., A.A., A. Vashkevich, M.E.G., S.B.S., S.M.G., A. Viswanathan), and Division of Behavioral Neurology (A.B.), Department of Neurology, Division of Neuropsychiatry, Department of Psychiatry (A.B.), Neuropathology Service, Department of Pathology (C.M.W.), and The Center for Human Genetic Research (G.J.F., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Medicine (D.R.), Faculty of Medicine, Naresuan University, Phitsanulok, Thailand; and Human Cortical Physiology and Stroke Neurorehabilitation Section (O.O.A.), NINDS/NIH, Bethesda, MD.
Anand
A
Viswanathan
D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics; D016657:Cerebral Amyloid Angiopathy; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012008:Recurrence; D012806:Siderosis / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D018709:Statistics, Nonparametric; D013345:Subarachnoid Hemorrhage / Q000000981:diagnostic imaging / Q000209:etiology; D015898:Tomography Scanners, X-Ray Computed
D001057:Apolipoproteins E
J Neurol. 2013 Jan;260(1):176-81
22820723
N Engl J Med. 2006 Aug 10;355(6):549-59
16899775
Cerebrovasc Dis. 2015;39(5-6):278-86
25871492
AJR Am J Roentgenol. 1987 Aug;149(2):351-6
3496763
JAMA. 2015 Sep 1;314(9):904-12
26325559
Surg Neurol. 2007 Oct;68(4):457-60
17905074
Arch Neurol. 2011 May;68(5):573-9
21220650
Stroke. 2015 Jun;46(6):1533-40
25953372
Arch Neurol. 1984 Mar;41(3):330-3
6696653
Neurology. 2013 Nov 5;81(19):1666-73
24107862
BMC Neurol. 2014 Apr 10;14:80
24720867
Stroke. 2013 Nov;44(11):3013-7
24008570
J Neurol Neurosurg Psychiatry. 2014 Jun;85(6):660-7
24262916
Rinsho Shinkeigaku. 2007 Jan;47(1):42-6
17491336
Neurology. 2001 Feb 27;56(4):537-9
11222803
AJNR Am J Neuroradiol. 2008 Jan;29(1):184-6
17947366
Neurology. 2006 Jan 24;66(2):206-9
16434655
Neurology. 2004 Nov 9;63(9):1606-12
15534243
N Engl J Med. 2000 Jan 27;342(4):240-5
10648765
Stroke. 1995 Jul;26(7):1189-92
7604411
Lancet Neurol. 2013 Aug;12(8):822-38
23867200
Neurology. 2004 Sep 28;63(6):1059-64
15452298
Neurology. 2014 Nov 11;83(20):1838-43
25320098
Neuropathology. 2003 Dec;23(4):254-61
14719539
Stroke. 2004 Jun;35(6):1415-20
15073385
Neurology. 2010 Aug 24;75(8):693-8
20733144
Brain. 2015 Aug;138(Pt 8):2126-39
26115675
Neuropathology. 2012 Feb;32(1):38-43
21535227
Neurology. 2010 Apr 27;74(17):1346-50
20421578
Stroke. 2010 Feb;41(2):394-6
20044530
Neurology. 2016 May 31;86(22):2034-41
27164693
Eur J Neurol. 2011 Apr;18(4):597-603
21040231
Ann Neurol. 1995 Aug;38(2):254-9
7654074