Course of cerebral amyloid angiopathy-related inflammation.
BACKGROUND
A subset of patients with cerebral amyloid angiopathy (CAA) present with cognitive symptoms, seizures, headaches, T2-hyperintense MRI lesions, and neuropathologic evidence of CAA-associated vascular inflammation.


OBJECTIVE
To analyze the risk factors, diagnostic characteristics, and long-term course of this disorder.


METHODS
We assessed 14 consecutive patients with pathologically diagnosed CAA-related inflammation, 12 with available neuroimaging and follow-up data. Patients were evaluated for MRI appearance, APOE genotype, and clinical course over a 46.8 +/- 29.1-month follow-up.


RESULTS
Baseline MRI scans were characterized by asymmetric T2-hyperintense lesions extending to the subcortical white matter and occasionally the overlying gray matter, with signal properties suggesting vasogenic edema. Subjects could be divided into three groups based on response to immunosuppressive treatment: monophasic improvement (7/12), initial improvement followed by symptomatic relapse (3/12), and no evident response to treatment (2/12). The volume of MRI hyperintensities correlated with the severity of clinical symptoms. One patient experienced symptomatic intracerebral hemorrhage within a region of recurrent MRI hyperintensity. The APOE epsilon4/epsilon4 genotype was strongly associated with CAA-related inflammation, present in 76.9% (10/13) of subjects vs 5.1% (2/39) with symptomatic but noninflammatory CAA (p < 0.0001).


CONCLUSIONS
Cerebral amyloid angiopathy-related inflammation represents a clinically, pathologically, radiographically, and genetically distinct disease subtype with implications for clinical practice and ongoing immunotherapeutic approaches to Alzheimer disease.
Kinnecom
C
C
Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Lev
M H
MH
Wendell
L
L
Smith
E E
EE
Rosand
J
J
Frosch
M P
MP
Greenberg
S M
SM
D000368:Aged; D000544:Alzheimer Disease / Q000276:immunology / Q000628:therapy; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D053327:Apolipoprotein E4 / Q000235:genetics; D016657:Cerebral Amyloid Angiopathy / Q000150:complications* / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D003072:Cognition Disorders / Q000209:etiology; D015331:Cohort Studies; D015140:Dementia, Vascular / Q000209:etiology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006261:Headache / Q000209:etiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011859:Radiography; D012307:Risk Factors; D012640:Seizures / Q000209:etiology; D014657:Vasculitis / Q000209:etiology* / Q000473:pathology
D000893:Anti-Inflammatory Agents; D053327:Apolipoprotein E4