脑淀粉样血管病,诊断标准

Clinical diagnosis of

cerebral amyloid angiopathy:Validation of the Boston Criteria Article abstract—The authors performed clinical–pathologic correlation to assess the validity of the Boston diagnostic criteria for cerebral amyloid angiopathy(CAA).Thirteen subjects were diagnosed clinically with probable CAA from among39patients with available pathologic tissue in a prospective cohort of subjects agedՆ55years with primary lobar hemorrhage.All13 individuals were confirmed neuropathologically as having CAA.This small pathologic series indicates that the diagnosis of probable CAA can be made during life with high accuracy.

NEUROLOGY2001;56:537–539

Katherine A.Knudsen,BA;Jonathan Rosand,MD;Diane Karluk,MD;and Steven M.Greenberg,MD,PhD

Cerebral amyloid angiopathy(CAA)has generally been diagnosed by postmortem examination.Al-though this disorder can also be identified during life by the examination of an evacuated hematoma or brain biopsy specimen,tissue samples from living patients are typically unavailable.A reliable,nonin-vasive method for diagnosing CAA would facilitate both clinical decision making and future clinical drug trials for this untreatable disorder.

With these goals in view,a group of stroke neurol-ogists in the Boston area1proposed criteria for the diagnosis of CAA(see the Appendix).The criteria were based on the tendency for CAA-related hemor-rhages to be multiple and to occur primarily in corti-cal and corticosubcortical(or lobar)brain regions.2 According to these criteria,the diagnosis of probable CAA could be reached in elderly patients with at least two acute or chronic lobar hemorrhagic lesions and without other definite cause of intracerebral hemorrhage(ICH).

The validity of the Boston criteria has previously been supported by studies comparing the frequencies of the APOE⑀2and⑀4alleles in groups of patients with clinically diagnosed and pathologically diagnosed CAA.3We now present the more direct approach of clinical–pathologic correlation for validating these criteria.

Methods.We identified all available brain tissue speci-mens from our prospective cohort of patients agedՆ55 years with primary lobar ICH admitted or referred to the Massachusetts General Hospital(MGH)or Spaulding Re-habilitation Hospital(SRH)between July1994and March 2000.To avoid a systematic bias,we excluded patients who had a pathologic diagnosis of CAA at the time of referral to MGH or SRH.Of233eligible patients,39(17%)were determined to have available pathologic samples contain-ing cerebral vessels.

Each of these primary lobar ICH patients was diag-nosed on clinical and radiographic grounds with probable or possible CAA according to the Boston criteria(see the Appendix).The diagnostic radiographic studies consisted of gradient-echo MRI scans in15patients,MRI without gradient echo in seven,and CT scans alone in17.All images were obtained prior to or within1week of the acquisition of the neuropathologic sample,and all were evaluated for this study by a stroke neurologist(J.R.)with-out knowledge of the pathologic diagnosis.Four patients taking warfarin with an international normalized ratio (INR)Յ3.0were diagnosed with probable CAA,whereas an additional four patients were instead diagnosed with possible CAA because of an INRϾ3.0.

Neuropathologic specimens were obtained from patients by postmortem brain examination(nϭ14),hematoma evacuation(nϭ21),or cortical biopsy(nϭ4).All samples were stained by conventional methods including Congo red and examined in random order by a neuropathologist (D.K.)blinded to clinical diagnosis.CAA was diagnosed as the cause of ICH in postmortem brains by the complete replacement of blood vessel walls with amyloid,cracking of the vessel wall(creating a“vessel-in-vessel”appearance), and at least one focus of paravascular blood leakage,with-out other definite source of hemorrhage.CAA was diag-nosed in hematoma or biopsy samples by complete replacement of a vessel wall with amyloid,an approach previously shown to correlate with CAA-related ICH with high specificity.4

Results.Of39primary lobar ICH patients with neuro-pathologic samples containing vessels,13met criteria for probable CAA(see the Appendix).The multiple hemor-rhagic lesions in these patients were demonstrated by CT or MRI scans performed at the time of each hemorrhage (nϭ5)or by gradient-echo MRI sequences(nϭ8)sensi-tive to old as well as recent hemorrhagic lesions.5,6 All13patients(100%)diagnosed clinically with proba-ble CAA demonstrated CAA pathologically(table1).Of the remaining26patients with possible CAA,16(62%)were pathologically diagnosed with CAA.No alternative patho-logic cause of hemorrhage was found in the10samples without CAA(including four full postmortem brain exami-nations).None of the pathologic specimens showed severe hypertensive vascular changes,vascular malformations,or saccular aneurysms.

The overall prevalence of CAA was29/39(74%).The

From the Clinical Trials Unit,Department of Neurology(K.Knudsen and

Drs.Rosand and Greenberg)and C.S.Kubik Laboratory for Neuropathology

(Dr.Karluk),Massachusetts General Hospital and Harvard Medical School,

Boston.

Supported by grants from the NIH(AG00725)and American Heart

Association.

Received July7,2000.Accepted in final form November4,2000.

Address correspondence and reprint requests to Dr.Steven M.Greenberg,

Neurology Clinical Trials Unit,Wang ACC836,Massachusetts General

Hospital,Boston,MA02114;e-mail greenberg@

Copyright©2001by AAN Enterprises,Inc.537