Yong-Bum Kim, M.D., Kwang-Ho Lee, M.D., Soo-Joo Lee, M.D., Duk-L. Na, M.D., Soo-Jin Cho, M.D., Chin-Sang Chung, M.D., Won-Yong Lee M.D.

Transcription

1 Usefulness of Apolipoprotein E 4 and Distribution of Petechial Hemorrhages in Differentiating between Cerebral Amyloid Angiopathy and Hypertensive Intracerebral Hemorrhage Yong-Bum Kim, M.D., Kwang-Ho Lee, M.D., Soo-Joo Lee, M.D., Duk-L. Na, M.D., Soo-Jin Cho, M.D., Chin-Sang Chung, M.D., Won-Yong Lee M.D. Department of Neurology, Samsung Medical Center, College of Medicine, Sungkyunkwan University B a c k g r o u n d : Cerebral amyloid angiopathy(caa) accounts for a significant proportion of spontaneous lobar hemorrhages in the elderly population but hypertension is responsible for most cases of deep-seated hemorrhage. Reportedly petechial hemorrhages(phs) can be associated with CAA or chronic hypertension. We determined the location of PHs and apolipoprotein E(APOE) genotype in intracerebral hemorrhage(ich) patients and tried to correlate them with CAA associated or hypertensive ICH. M e t h o d s : One hundred and sixty-two consecutive patients with primary ICH were evaluated clinically and by MRI. PHs were defined as small low-signal lesions(less than 1) seen on T2-weighted or gradient-echo MR images. ICH and PHs were divided into lobar(cortical-corticosubcortical), deep(basal ganglia, thalamus, pons, or cerebellum), or mixed. APOE genotype was determined by polymerase chain reaction. All 162 patients were classified into 4 groups: 1) probable CAA(multiple lobar bleeds without other cause), 2) possible CAA(single lobar bleed), 3) probable hypertensive ICH(deep bleed), and 4) mixed lobar and deep hemorrhages. R e s u l t s: Among 162 patients, 31 belonged to the probable and possible CAA groups and 17 of them showed PHs(7 lobar, 4 deep, 6 mixed). One hundred and twentytwo patients were the hypertensive ICH group and 63 of them had PHs(2 lobar, 10 mixed, 51 deep). Lobar PHs were more frequently observed in the probable and possible CAA group than the hypertensive ICH group(22.6%: 1.6%, p<0.01) while deep PHs were seen mainly in the hypertensive ICH group(41.8%: 12.9%, p<0.01) and these tendencies are also observed in the group who had taken both T2-weighted and gradient-echo MR images(64 patients). The frequency of hypertension was significantly lower in the probable and possible CAA groups with lobar PHs than in the hypertensive ICH group with deep PHs(57.1%: 98 %, n=7 & 51 respectively, p<0.01). APOE 4 frequency was: probable(freq. 0.25, n=2), possible CAA(freq. 0.21, n=7), hypertensive(freq , n=9), and mixed hemorrhages(freq , n=7). The frequency of APOE 4 of probable and possible CAA group seems to be higher than that of normal control(freq. 0.19, n=146). C o n c l u s i o n s : APOE 4 and PHs in lobar areas may be associated with hemorrhages restricted to lobar regions while hypertension and PHs in deep areas, with hemorrhages restricted to deep regions. J Kor Neurol Ass 17(1):32~37, 1999 Key Words : Amyloid angiopathy, Apolipoprotein E, Intracerebral hemorrhage, Petechial hemorrhage, Gradient-echo MRI Kwang-Ho Lee, M.D. 32 Copyright 1999 by the Korean Neurological Association

2 Figure 1. Lobar type petechial hemorrhages which are smaller than 1and observed in such regions as frontal, parietal, temporal or occipital lobe. J Kor Neurol Ass / Volume 17 / January,

3 Figure 2. Deep type petechial hemorrhages which are smaller than 1and observed in such regions as basal ganglia, thalamus, pons or cerebellum. Figure 3. Mixed type petechial hemorrhages 34 J Kor Neurol Ass / Volume 17 / January, 1999

4 Table 1. Distribution of petechial hemorrhages in each group. ICH; intracerebral hemorrhage, PHs; petechial hemorrhages Lobar PHs Mixed PHs Deep PHs No PHs Total Multiple lobar bleeds(group 1) Single lobar bleed(group 2) Multiple or single deep bleeds(group 3) Mixed bleeds(group 4) PHs; petechial hemorrhages Table 2. Distribution of petechial hemorrhages in each group(excluded the patients who were not evaluated by gradient-echo MRI). Lobar PHs Mixed PHs Deep PHs No PHs Total Multiple lobar bleeds(group 1) Single lobar bleed(group 2) Multiple or single deep bleeds(group 3) Mixed bleeds(group 4) PHs; petechial hemorrhages Table 3. Comparison of the frequency of hypertension between deep intracerebral hemorrhage(s) with deep petechial hemorrhages and lobar intracerebral hem - orrhage(s) with lobar petechial hemorrhages. Number of patients Frequency of hypertension Deep ICH(Group 3) % Lobar ICH(Group 1 & 2) % Deep ICH with deep PHs % Lobar ICH with lobar PHs % J Kor Neurol Ass / Volume 17 / January,

5 Table 4. The frequency of apolipoprotein E 4 in each hemorrhage group. Number of patients Genotyping was performed frequency of apolipoprotein E 4 allele Multiple lobar bleeds(group 1) % Single lobar bleed(group 2) % Multiple or single deep bleeds(group 3) % Mixed bleeds(group 4) % angiopathy. Neurology 1993;43: Okazakie H, Reagan TJ, Cambell RJ. Clinicopathologic studies of primary cerebral amyloid angiopathy. M a y o Clin Proc 1979;54: Fisher CM. Pathological observations in hypertensive 1995;38: Schmechel DE, Saunders AM, Strittmatter WJ et al. Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in lateonset Alzheimer disease. Proc Natl Acad Sci USA 1993; 90: Vinters HV. Cerebral amyloid angiopathy: A critical review. Stroke 1986;18: Vinters HV. Cerebral amyloid angiopathy. In: Barnett HJM, Mohr JP, Barnett SM, Yatsu FM eds. Stroke: pathophysiology, diagnosis, and management. 2nd ed. New York: Churchill Livingstone Inc., 1992, Greenberg SM, Vonsattel JPG, Stakes JW, Gruber M, Finklestein SP. The clinical spectrum of cerebral amyloid 05. Greenberg SM, Finklestein SP, Schaefer PW. Petechial hemorrhages accompanying lobar hemorrhage: Detection by gradient -echo MRI. Neurology 1996;46: cerebral hemorrhage. J Neuropathol Exp Neurol 1971;30: Greenberg SM, Rebeck GW, Vonsatel JPG, Gomez-Isla T, Hyman BT. Apolipoprotein E 4 and cerebral hemorrhage associated with amyloid angiopathy. Ann Neurol 09.,,. E. 1996;14: Kalaria RN, Premkumar DRD. Apolipoprotein E genotype and cerebral amyloid angiopathy. L a n c e t 1995 ; 346 : 36 J Kor Neurol Ass / Volume 17 / January, 1999

6 1424(letter). 11. Greenberg SM, Briggs ME, Hyman BT et al. Apolipoprotein E 4 is associated with the presence and earlier onset of hemorrhage in cerebral amyloid angiopathy. Stroke 1996;27: Nicoll JAR, Burnett C, Love S et al. High frequency of apolipoprotein E 2 allele in hemorrhage due to cerebral amyloid angiopathy. Ann Neurol 1997;41: Scharf J, Brauherr E, Forsting M, Sartor K. Significance of hemorrhagic lacunes on MRI in patients with hypertensive cerebrovascular disease and intracerebral hemorrhage. Neuroradiology 1994;36: Chan S, Kartha K, Yoon S, Desmond DW, Hilal SK. Multifocal hypointense cerebral lesions on gradient-echo MR are associated with chronic hypertension. AJNR 1996;17: Greenberg SM, Vonsatel JPG, Segal AZ et al. Association of apolipoprotein E 2 and vasculopathy in cerebral amyloid angiopathy. Neurology 1998;50: J Kor Neurol Ass / Volume 17 / January,