Vincent Scheumann1, Frank Schreiber2, Valentina Perosa3, Anne Assmann4, Christian Mawrin5, Cornelia Garz6, Hans-Jochen Heinze7, Michael Görtler8, Emrah Düzel9, Stefan Vielhaber10, Andreas Charidimou11, Stefanie Schreiber12. 1. Department of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120 Magdeburg, Germany. Electronic address: vincent.scheumann@st.ovgu.de. 2. Department of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120 Magdeburg, Germany; German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, 39120 Magdeburg, Germany. Electronic address: frank.schreiber@dzne.de. 3. Department of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120 Magdeburg, Germany; German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, 39120 Magdeburg, Germany; J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, 175 Cambridge Street, Boston, MA 02114, USA. Electronic address: valentina.perosa@med.ovgu.de. 4. Department of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120 Magdeburg, Germany. Electronic address: anne.assmann@med.ovgu.de. 5. Institute of Neuropathology, Otto-von-Guericke-University Magdeburg, Leipziger Straße 44, 39120 Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), Universitätsplatz 2, 39106 Magdeburg, Germany. Electronic address: christian.mawrin@med.ovgu.de. 6. German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, 39120 Magdeburg, Germany; Leibniz Institute for Neurobiology (LIN), Brenneckestraße, 39118 Magdeburg, Germany. Electronic address: cornelia.garz@med.ovgu.de. 7. Department of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120 Magdeburg, Germany; German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, 39120 Magdeburg, Germany; Leibniz Institute for Neurobiology (LIN), Brenneckestraße, 39118 Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), Universitätsplatz 2, 39106 Magdeburg, Germany. Electronic address: hans-jochen.heinze@med.ovgu.de. 8. Department of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120 Magdeburg, Germany. Electronic address: Michael.Goertler@med.ovgu.de. 9. German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, 39120 Magdeburg, Germany; Leibniz Institute for Neurobiology (LIN), Brenneckestraße, 39118 Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), Universitätsplatz 2, 39106 Magdeburg, Germany; Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke-University Magdeburg, Leipziger Straße 44, 39120 Magdeburg, Germany. Electronic address: emrah.duezel@dzne.de. 10. Department of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120 Magdeburg, Germany; German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, 39120 Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), Universitätsplatz 2, 39106 Magdeburg, Germany. Electronic address: stefan.vielhaber@med.ovgu.de. 11. Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. Electronic address: acharidimou@mgh.harvard.edu. 12. Department of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120 Magdeburg, Germany; German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, 39120 Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), Universitätsplatz 2, 39106 Magdeburg, Germany. Electronic address: stefanie.schreiber@med.ovgu.de.
Abstract
OBJECTIVE: To investigate underlying cerebral small vessel disease (CSVD) in patients with mixed cerebral hemorrhages patterns and phenotype them according to the contribution of the two most common sporadic CSVD subtypes: cerebral amyloid angiopathy (CAA) vs. hypertensive arteriopathy (HA). METHODS: Brain MRIs of patients with intracerebral hemorrhages (ICHs) and/or cerebral microbleeds (CMBs) were assessed for the full spectrum of CSVD markers using validated scales: ICHs, CMBs, cortical superficial siderosis (cSS), white matter hyperintensities, MRI-visible perivascular spaces (PVS). PVS predominance pattern was grouped as centrum-semiovale (CSO)-PVS predominance, basal-ganglia (BG)-PVS predominance, CSO-PVS and BG-PVS equality. Patients with mixed cerebral hemorrhages were classified into mixed CAA-pattern or mixed HA-pattern according to the existence of cSS and/or a CSO-PVS predominance pattern and comparisons were performed. RESULTS: We included 110 patients with CAA (strictly lobar ICHs/CMBs), 33 with HA (strictly deep ICHs/CMBs) and 97 with mixed lobar/deep ICHs/CMBs. Mixed patients were more similar to HA with respect to their MRI-CSVD markers, vascular risk profile and cerebrospinal fluid (CSF) measures. In the mixed patients, 33 (34%) had cSS, a CSO-PVS predominance pattern, or both, and were defined as mixed CAA-pattern cases. The mixed CAA-pattern patients were more alike CAA patients regarding their MRI-CSVD markers, CSF and genetic profile. CONCLUSION: Our findings suggest that the heterogeneous group of patients with mixed cerebral hemorrhages distribution can be further phenotyped according to the predominant underlying CSVD. cSS presence and a CSO-PVS predominance pattern could serve as strongly suggestive markers of a contribution from CAA among patients with mixed hemorrhages.
OBJECTIVE: To investigate underlying cerebral small vessel disease (CSVD) in patients with mixed cerebral hemorrhages patterns and phenotype them according to the contribution of the two most common sporadic CSVD subtypes: cerebral amyloid angiopathy (CAA) vs. hypertensive arteriopathy (HA). METHODS: Brain MRIs of patients with intracerebral hemorrhages (ICHs) and/or cerebral microbleeds (CMBs) were assessed for the full spectrum of CSVD markers using validated scales: ICHs, CMBs, cortical superficial siderosis (cSS), white matter hyperintensities, MRI-visible perivascular spaces (PVS). PVS predominance pattern was grouped as centrum-semiovale (CSO)-PVS predominance, basal-ganglia (BG)-PVS predominance, CSO-PVS and BG-PVS equality. Patients with mixed cerebral hemorrhages were classified into mixed CAA-pattern or mixed HA-pattern according to the existence of cSS and/or a CSO-PVS predominance pattern and comparisons were performed. RESULTS: We included 110 patients with CAA (strictly lobar ICHs/CMBs), 33 with HA (strictly deep ICHs/CMBs) and 97 with mixed lobar/deep ICHs/CMBs. Mixed patients were more similar to HA with respect to their MRI-CSVD markers, vascular risk profile and cerebrospinal fluid (CSF) measures. In the mixed patients, 33 (34%) had cSS, a CSO-PVS predominance pattern, or both, and were defined as mixed CAA-pattern cases. The mixed CAA-pattern patients were more alike CAA patients regarding their MRI-CSVD markers, CSF and genetic profile. CONCLUSION: Our findings suggest that the heterogeneous group of patients with mixed cerebral hemorrhages distribution can be further phenotyped according to the predominant underlying CSVD. cSS presence and a CSO-PVS predominance pattern could serve as strongly suggestive markers of a contribution from CAA among patients with mixed hemorrhages.
Authors: Wilhelm Hußler; Lukas Höhn; Christopher Stolz; Stefan Vielhaber; Cornelia Garz; Friedhelm C Schmitt; Eckart D Gundelfinger; Stefanie Schreiber; Constanze I Seidenbecher Journal: Front Cell Neurosci Date: 2022-04-11 Impact factor: 5.505