Correspondence
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Charidimou A, Gang Q, Werring DJ. Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry 2012; 83: 124–37. Vinters HV. Cerebral amyloid angiopathy. A critical review. Stroke 1987; 18: 311–24. Greenberg SM, Vonsattel JP, Stakes JW, Gruber M, Finklestein SP. The clinical spectrum of cerebral amyloid angiopathy: presentations without lobar hemorrhage. Neurology 1993; 43: 2073–79. Greenberg SM, Nandigam RN, Delgado P, et al. Microbleeds versus macrobleeds: evidence for distinct entities. Stroke 2009; 40: 2382–86. Charidimou A, Jäger RH, Fox Z, et al. Prevalence and mechanisms of cortical superficial siderosis in cerebral amyloid angiopathy. Neurology 2013; 81: 626–32.
Authors’ reply We appreciate the insightful comments from Andreas Charidimou and Hans Rolf Jäger regarding the distinct phenotypes associated with cerebral amyloid angiopathy and their effect on selection of outcome markers for clinical trials.1 As the authors correctly note, cerebral amyloid angiopathy is a complex entity that can follow several different pathways, each associated with its own cluster of biomarkers. It
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follows that a key factor in selection of outcome markers for a trial of cerebral amyloid angiopathy is the pathophysiological target of the particular treatment under investigation. Although studies of phenotypes of cerebral amyloid angiopathy often focus on the extreme forms (such as microbleeders and macrobleeders), most patients probably fall into a mixed category in which various cerebral amyloid angiopathy-related vascular processes coexist. We therefore encourage investigators of cerebral amyloid angiopathy to collect and analyse a full range of measures of focal injury and overall brain structure and function. We declare that we have no competing interests.
*Steven M Greenberg, Rustam Al-Shahi Salman, Geert Jan Biessels, Mark van Buchem, Charlotte Cordonnier, Jin-Moo Lee, Joan Montaner, Julie A Schneider,
MGH Stroke Research Center, Massachusetts General Hospital, Boston, MA 02114, USA (SMG); Division of Clinical Neurosciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK (RAS); Brain Centre Rudolf Magnus, University Medical Center of Utrecht, Utrecht, Netherlands (GJB); Department of Radiology, Leiden University Medical Center, Leiden, Netherlands (MvB); Department of Neurology, Universite Lille Nord de France, Lille University Hospital, Lille, France (CC); Department of Neurology,Department of Radiology, and Department of Biomedical Engineering, Washington University School of Medicine, St Louis, MO, USA (J-ML); Department of Neurology, Vall d’Hebron University Hospital and Research Institute, Autonomus University of Barcelona, Barcelona, Spain (JM); Department of Pathology and Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA (JAS); Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada (EES); Department of Radiology and Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands (MV); and UCL Institute of Neurology, London, UK (DJW) 1
Greenberg SM, Salman RA, Biessels GJ, et al. Outcome markers for clinical trials in cerebral amyloid angiopathy. Lancet Neurol 2014; 13: 419–28.
Eric E Smith, Meike Vernooij, David J Werring [email protected]
www.thelancet.com/neurology Vol 13 June 2014
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Charidimou A, Gang Q, Werring DJ. Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry 2012; 83: 124–37. Vinters HV. Cerebral amyloid angiopathy. A critical review. Stroke 1987; 18: 311–24. Greenberg SM, Vonsattel JP, Stakes JW, Gruber M, Finklestein SP. The clinical spectrum of cerebral amyloid angiopathy: presentations without lobar hemorrhage. Neurology 1993; 43: 2073–79. Greenberg SM, Nandigam RN, Delgado P, et al. Microbleeds versus macrobleeds: evidence for distinct entities. Stroke 2009; 40: 2382–86. Charidimou A, Jäger RH, Fox Z, et al. Prevalence and mechanisms of cortical superficial siderosis in cerebral amyloid angiopathy. Neurology 2013; 81: 626–32.
Authors’ reply We appreciate the insightful comments from Andreas Charidimou and Hans Rolf Jäger regarding the distinct phenotypes associated with cerebral amyloid angiopathy and their effect on selection of outcome markers for clinical trials.1 As the authors correctly note, cerebral amyloid angiopathy is a complex entity that can follow several different pathways, each associated with its own cluster of biomarkers. It
540
follows that a key factor in selection of outcome markers for a trial of cerebral amyloid angiopathy is the pathophysiological target of the particular treatment under investigation. Although studies of phenotypes of cerebral amyloid angiopathy often focus on the extreme forms (such as microbleeders and macrobleeders), most patients probably fall into a mixed category in which various cerebral amyloid angiopathy-related vascular processes coexist. We therefore encourage investigators of cerebral amyloid angiopathy to collect and analyse a full range of measures of focal injury and overall brain structure and function. We declare that we have no competing interests.
*Steven M Greenberg, Rustam Al-Shahi Salman, Geert Jan Biessels, Mark van Buchem, Charlotte Cordonnier, Jin-Moo Lee, Joan Montaner, Julie A Schneider,
MGH Stroke Research Center, Massachusetts General Hospital, Boston, MA 02114, USA (SMG); Division of Clinical Neurosciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK (RAS); Brain Centre Rudolf Magnus, University Medical Center of Utrecht, Utrecht, Netherlands (GJB); Department of Radiology, Leiden University Medical Center, Leiden, Netherlands (MvB); Department of Neurology, Universite Lille Nord de France, Lille University Hospital, Lille, France (CC); Department of Neurology,Department of Radiology, and Department of Biomedical Engineering, Washington University School of Medicine, St Louis, MO, USA (J-ML); Department of Neurology, Vall d’Hebron University Hospital and Research Institute, Autonomus University of Barcelona, Barcelona, Spain (JM); Department of Pathology and Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA (JAS); Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada (EES); Department of Radiology and Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands (MV); and UCL Institute of Neurology, London, UK (DJW) 1
Greenberg SM, Salman RA, Biessels GJ, et al. Outcome markers for clinical trials in cerebral amyloid angiopathy. Lancet Neurol 2014; 13: 419–28.
Eric E Smith, Meike Vernooij, David J Werring [email protected]
www.thelancet.com/neurology Vol 13 June 2014
