Hypertensive ICH in young people

1. ISSN: 1524-4628
Copyright © 2006 American Heart Association. All rights reserved. Print ISSN: 0039-2499. Online
Stroke is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX 72514
DOI: 10.1161/01.STR.0000248766.22741.4b
2006;37;2946-2950; originally published online Nov 9, 2006;Stroke
Fernando Barinagarrementería
Padilla-Martínez, Jorge Villarreal-Careaga, Carlos Cantú, Antonio Arauz and
José L. Ruiz-Sandoval, Samuel Romero-Vargas, Erwin Chiquete, Juan J.
Age-Related Clinical Differences
Hypertensive Intracerebral Hemorrhage in Young People: Previously Unnoticed
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2. Hypertensive Intracerebral Hemorrhage in Young People
Previously Unnoticed Age-Related Clinical Differences
Jose´ L. Ruiz-Sandoval, MD; Samuel Romero-Vargas, MD; Erwin Chiquete, MD, PhD;
Juan J. Padilla-Martı´nez, MD; Jorge Villarreal-Careaga, MD; Carlos Cantu´, MD, MSc;
Antonio Arauz, MD, MSc; Fernando Barinagarrementerı´a, MD
Background and Purpose—Hypertensive intracerebral hemorrhage (ICH) in young people has been the object of only
succinct analyses. Therefore, it is unclear whether extrapolation of the information obtained from older patients is also
valid for the young. Here we describe young persons with hypertensive ICH and compare them with their older
counterparts to determine whether age-related clinical differences exist.
Methods—From 1988 to 2004, we studied 35 consecutive young patients with ICH (60% men; mean age, 33 years; range,
15 to 40 years) for whom the etiology of the brain hemorrhage was hypertension. For clinical comparisons, sex-matched
persons with hypertensive ICH, aged Ͼ40 years, were randomly selected by a factor of 3:1 (nϭ105).
Results—Essential hypertension was present in 26 (74%) young patients and secondary hypertension in 9 (26%), with
renovascular hypertension being the most common cause (nϭ5, 55%). Compared with older patients, the young had
higher blood pressures, smaller hemorrhage volumes, lower rates of ventricular extensions (for all, PϽ0.05), and
different distribution pattern of ICHs (Pϭ0.05), without cerebellar and lobar locations. Thirty-day mortality was
markedly lower in the young than in older persons (Pϭ0.001), nevertheless at the expense of more incapacitating
disabilities.
Conclusions—Young people presenting with hypertensive ICH differ in clinical characteristics and have a different
prognosis when compared with their older counterparts. These findings suggest underlying age-related differences in
disease pathogenesis. (Stroke. 2006;37:2946-2950.)
Key Words: aging Ⅲ intracerebral hemorrhage Ⅲ hypertension Ⅲ risk factors Ⅲ young people
Intracerebral hemorrhage (ICH) accounts for 10% to 23%
of strokes,1,2 with hypertension being the single most
important risk factor in middle-aged and elderly persons.3–5
Current knowledge about hypertensive ICH in the young is
derived mainly from studies on all-cause ICH, which have
reported variable frequencies ranging from 11% to 64% and
providing only brief conclusions about topography and prog-
nosis.5–15 The other well-characterized clinical and radiolog-
ical characteristics of middle-aged and elderly ICH patients
are generally unknown for their younger counterparts. There-
fore, extrapolation of the information obtained from older
people might not be valid for young persons.
In view of the scarce information on these issues, we aimed
to analyze hypertensive ICH in young people, their hyperten-
sion profile, clinical condition, and outcome. Also, to identify
features that would suggest underlying age-related differences in
disease pathogenesis, we compared the young patients with their
older counterparts. Our hypothesis was that hypertensive ICH of
the young differs in clinical characteristics and has a different
prognosis, when compared with that seen in older people.
Subjects and Methods
Study Population and Design
From January 1988 to December 2004, we analyzed 294 consecutive
patients with symptomatic ICH who were Ͻ40 years old. From 1988
to 1998, the Instituto Nacional de Neurologı´a y Neurocirugı´a
(Mexico City, Distrito Federal, Mexico) included 244 patients, and
from 1999 to 2004, the Hospital Civil de Guadalajara Fray Antonio
Alcalde (Guadalajara, Jalisco, Mexico) included 50 patients in the
respective research databases. Of the 294 young patients, hyperten-
sion was the cause of ICH in 35 (12%). To identify possible
age-related clinical differences, sex-matched persons with hyperten-
sive ICH, aged Ͼ40 years, were randomly selected by a factor of 3:1
Received April 22, 2006; final revision received July 17, 2006; accepted July 19, 2006.
From the Department of Neurology and Neurosurgery (J.L.R.-S., S.R.-V., E.C., J.J.P.-M.), Hospital Civil de Guadalajara Fray Antonio Alcalde, and
the Department of Neurosciences, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, and the Stroke Clinic (J.V.-C.,
C.C., A.A., F.B.), Instituto Nacional de Neurologı´a y Neurocirugı´a, Mexico City, Mexico.
Dr Jorge Villarreal-Careaga is currently at the Hospital General de Culiaca´n; Culiaca´n, Mexico. Dr Carlos Cantu´ is currently at the Department of
Neurology, Instituto Nacional de Ciencias Me´dicas y de la Nutricio´n Salvador Zubira´n, Mexico City, Mexico. Dr Fernando Barinagarrementerı´a is
currently at the Department of Neurology, Hospital A´ ngeles de Quere´taro, Quere´taro, Mexico.
Correspondence and reprint requests to Dr Jose´ Luis Ruiz-Sandoval, Servicio de Neurologı´a y Neurocirugı´a, Hospital Civil de Guadalajara Fray
Antonio Alcalde, Hospital 278, Guadalajara, Jalisco, Me´xico CP44280. E-mail jorusan@mexis.com, or Dr Fernando Barinagarrementerı´a Aldatz,
Neurologı´a, Hospital A´ ngeles, Quere´taro. Bernardino del Razo 21, Santiago de Quere´taro, Qro, Me´xico. E-mail fbarinaga@infosel.net.mx
© 2006 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org DOI: 10.1161/01.STR.0000248766.22741.4b
2946

3. (nϭ105). The same inclusion criteria were applied for all patients.
The internal Ethics Committee of our hospitals approved the study,
and informed consent was obtained from all patients or their closest
relatives.
Operational Definitions
In all cases included, ICH was defined as a sudden, focal, neurolog-
ical deficit with intraparenchymal hemorrhage seen on head com-
puted tomography (CT) scans. Hypertensive status was defined as a
patient history of hypertension, with or without treatment, or
averaged readings of systolic blood pressure (SBP) Ͼ140 mm Hg or
of diastolic (DBP) Ͼ90 mm Hg, sustained for Ͼ2 weeks after the
hospital admission and confirmed during follow-up, if suitable.16
Other potential causes of ICH were excluded. The BP readings
obtained at presentation to the Emergency Department were consid-
ered for analyses to evaluate the discrete point of evolution of the
ICH in which the first clinical evaluations and decisions were
performed. Brain hemorrhage volume was calculated by analysis of
CT scans according to the ABC/2 method.17 Obesity was defined as
a body mass index Ն30 kg/m2
, smoking habit as the consumption of
Ն5 cigarettes at least 2 days per week during 12 months or more, and
alcoholism as Ͼ2 alcoholic drinks per day. Mean arterial pressure
(MAP) was calculated from the BP measurement on admittance to
the Emergency Department as follows: MAPϭDBPϩ0.412
(SBPϪDBP).18 Every young patient received an exhaustive clinical,
radiological, and laboratory assessment for secondary hypertension.
The Sokolow-Lyon criteria were used to define findings as sugges-
tive of left ventricular hypertrophy on the ECG.19 The patient’s
functional status was evaluated at hospital discharge and during
follow-up by using the Glasgow Outcome Scale.20
Data Analysis
Pearson ␹2
and Fisher exact test were used to assess nominal
variables in bivariate analyses. To compare quantitative variables
distributed between the 2 groups, Student t test and the Mann-
Whitney U test were performed for the distributions of parametric
and nonparametric variables, respectively. Pearson correlation was
used for continuous variables. All probability values were 2-sided
and considered significant when PϽ0.05. The SPSS (SPSS Inc)
v12.0 statistical package was used for all calculations and the process
of randomization and selection of the comparison group.
Results
We studied 35 consecutive young patients with hypertensive
ICH, 21 (60%) men and 14 (40%) women. MeanϮSD age
was 33Ϯ6.2 years (range, 15 to 40 years). One (3%) patient
was Ͻ20 years, 11 (31%) were between 21 and 30 years, and
23 (66%) were between 31 and 40 years. In addition to the
head CT scan, nine (26%) patients also underwent magnetic
resonance imaging and 14 (40%) were investigated further
with conventional cerebral angiography. Three (8.6%) pa-
tients had a history of prior ICH.
Hypertension Profile
Twenty-seven (77%) patients had known their hypertensive
status at the time of ICH, and in 8 (23%) the diagnosis of
hypertension was performed while hospitalized and con-
firmed during follow-up. In the 27 patients with antecedent
hypertension, the mean time from the diagnosis to ICH was
43 months (range, 1 month to 20 years); in 4 (15%) patients,
this period was Ͻ1 year; in 16 (59%), 1 to 5 years; and in 7
(26%), Ͼ5 years. Twenty (74%) patients had received phar-
macological treatment, and of them, only 7 (35%) declared to
be at least 80% compliant with their antihypertensive
regimen. The ICH volume was higher in patients without
treatment than in those with antihypertensive medication
(Table 1).
By ECG records and chest films review, evidence of left
ventricular hypertrophy was found in 28 (80%) patients. A
secondary cause of hypertension was identified in 9 (26%)
patients, renal artery stenosis being the cause in 5 (1 of them
with Takayasu disease) and Cushing syndrome, aortic coarc-
tation, primary aldosteronism, and pheochromocytoma in 1
case each.
ICH Features and Outcome
The brain hematomas were located in the putamen in 18
(51%) patients, the thalamus in 9 (26%), the pons in 5 (14%),
and the medulla, midbrain, and caudate nucleus in 1 (3%)
case each. Extension into the ventricular system occurred in
10 (29%) patients, 6 of them with hemorrhage in the thalamus,
3 in the putamen, and 1 in the caudate nucleus. The mean time
of hospitalization was 14 days (range, 0 to 43 days). Twenty-five
(71%) patients received medical treatment for ICH and 10
(29%), a neurosurgical procedure (hematoma evacuation in 4
and ventriculostomy alone in 5; 1 patient received both proce-
dures). In-hospital death occurred in 8 (23%) patients, 6 (17%)
were discharged with total dependence on others for daily
activities, and 16 (46%) were discharged with severe and 5
(14%) with mild disabilities. No patient was discharged with
complete recovery. The patients who survived to discharge lived
for at least 30 days; therefore, both in-hospital and 30-day
mortality was the same. MAP was higher in patients who had
died than in survivors at 30 days (170.8 versus 144.9 mm Hg,
respectively; Pϭ0.047). Twenty-six (96%) of the 27 survivors
had at least 1 follow-up visit. The mean follow-up period was
18.7 months (range, 1 to 96 months). At the last follow-up visit,
only 4 (15%) patients finally achieved total recovery, 13 (50%)
remained with moderate dependence, and 6 (23%) remained
TABLE 1. Clinical Characteristics and Outcome of the 35
Young Patients With Hypertensive ICH, According to
Antihypertensive Treatment
Characteristic
Antihypertensive Treatment
P*Present (nϭ20) Absent (nϭ15)
Age, median (SD), y 33.3 (6.6) 33.4 (5.8) 0.93
Male, n (%) 10 (50) 11 (73) 0.16
BP profile at hospital admission
SBP, mean (SD), mm Hg 197.55 (49.6) 172.93 (35.9) 0.11
DBP, mean (SD), mm Hg 125.20 (22.4) 126.00 (35.0) 0.93
MAP, mean (SD), mm Hg 155.01 (31.6) 145.34 (34.2) 0.39
ICH characteristics and outcome
ICH volume, mean (SD), cm3
8.8 (6.7) 31.8 (12.2) 0.006
Irruption to ventricles, n (%) 7 (35) 3 (20) 0.33
Disabilities, n (%)† 12 (60) 10 (67) 0.46
Disabilities or death
at 30 days, n (%)
18 (90) 12 (80) 0.40
30-day mortality, n (%) 6 (30) 2 (13) 0.42
*P value for differences between patients with and without antihypertensive
treatment; Pearson ␹2
, Fisher’s exact test, Student t test, or Mann-Whitney U
test, as appropriate.
†A Glasgow Outcome Scale classification of II or III.
Ruiz-Sandoval et al Hypertensive ICH in Young People 2947

4. with total dependence on others for activities of daily living.
Four (15.4%) of the 26 patients with suitable follow-up experi-
enced rebleeding during this period, 1 of them with a history of
prior ICH. Among the 3 patients without a history of ICH, the
pattern of recurrence was ganglia-ganglia in 2 and brain stem–
ganglia in 1. The patient with prior ICH presented with 2
rebleeding episodes during an 8-month outpatient follow-up, and
all hematomas were located in the basal ganglia. This 39-year-
old man had an abdominal pheochromocytoma and was dis-
charged in a vegetative state after the last event.
Young Versus Older Patients
Compared with older patients, the young had a higher
frequency of alcoholism and fewer cases of diabetes mellitus
(Table 2). Notably, the BP readings were higher in the young
than in older persons (Table 2); however, there were smaller
volumes of the hematomas and fewer cases of ventricular
involvement. Thirty-day mortality was markedly lower in
young patients than in the older, nevertheless at the expense
of a high number of cases with incapacitating disabilities
(Table 2). Compared with older persons, the young had a
different pattern of ICH location, with more brainstem
hematomas and without the occurrence of lobar or cerebellar
ICH (the Figure).
Discussion
Hypertensive ICH in young people is relatively uncommon
when other putative causes are excluded by an exhaustive
investigative protocol. We observed few cases before the
third decade of life, which underscores the association of age
with both hypertension and brain hemorrhage.
Hypertension Profile of the Young
The frequency of secondary hypertension in our young cohort
was higher than that reported for hypertensive persons with-
out ICH.21 Because the screening protocol for secondary
hypertension is not systematically practiced in our centers for
all persons, we could not determine the frequency of second-
ary hypertension in the older group. Nevertheless, secondary
hypertension causing ICH might be more frequent in young
people than it is in older persons, an issue that, however,
needs more study. Moreover, despite the relatively short
period between the diagnosis of hypertension and the occur-
rence of ICH in the young cohort, we found features of
target-organ damage commonly attributed to chronic expo-
sure to hypertension.22
Clinical and Radiological Age-Related Differences
At admission to the Emergency Department, the young had
higher BP readings than the older patients. The reason for this
aggravated BP profile in the young at hospital presentation
might be due to either to hyperactivity of the autoregulation
mechanisms of perfusion in response to brain damage23–25 or
a distinct pattern of hypertension of the young (ie, secondary
hypertension), compared with older patients. The young
TABLE 2. Risk Factors, Clinical Characteristics, and Outcome of 35 Young Patients and 105 Sex-Matched
Persons With Hypertensive ICH and >40 Years
Variables All Patients
Persons Aged Persons Aged
P*
Յ40 Years
(nϭ35)
Ͼ40 Years
(nϭ105)
Age, median (range), y 57 (18–99) 35 (18–40) 65 (42–99) Ͻ0.001
Male, n (%) 84 (60) 21 (60) 63 (60) Ͼ0.99
Risk factors
Obesity, n (%) 62 (44) 18 (51) 44 (42) 0.33
Alcoholism, n (%) 23 (16) 10 (29) 13 (12) 0.02
Smoking habit, n (%) 29 (21) 5 (14) 24 (23) 0.28
Diabetes mellitus, n (%) 29 (21) 3 (9) 26 (25) 0.04
Previous ICH, n (%) 17 (12) 3 (9) 14 (13) 0.45
BP profile at hospital admission
SBP, mean (SD), mm Hg 160.86 (68.1) 187 (45.3) 152.15 (72.3) 0.008
DBP, mean (SD), mm Hg 97.32 (41.1) 125.54 (28) 87.91 (40.5) Ͻ0.001
MAP, mean (SD), mm Hg 123.50 (51.1) 150.86 (32.6) 114.38 (52.9) Ͻ0.001
ICH characteristics and outcome
ICH volume, mean (SD), cm3
32.9 (32.4) 20.3 (15.3) 34.1 (33.4) 0.03
Irruption to ventricles, n (%) 74 (53) 10 (29) 64 (61) 0.001
Surgical treatment, n (%)† 67 (48) 10 (29) 57 (54) 0.008
Severe disabilities, n (%)‡ 48 (34) 22 (81) 26 (56) 0.03
30-day mortality, n (%) 67 (48) 8 (23) 59 (56) 0.001
Severe disabilities or 30-day mortality, n (%) 115 (82) 30 (86) 85 (81) 0.52
*P value for differences between patients aged Յ40 years and older patients; Pearson ␹2
, Fisher’s exact test, Student t test, or
Mann-Whitney U test, as appropriate.
†Hematoma evacuation, ventriculostomy, or both.
‡A Glasgow Outcome Scale classification of II or III.
2948 Stroke December 2006

5. cohort and their older counterparts differed in the location
pattern of the brain hematomas. These differences in ICH
location might be related to the effect of the aging process on
the cerebral blood vessels.26–28 Thus, on one hand, more ICHs
located in deep regions of the brain were observed in young
persons, and on the other, more lobar hematomas were found
in older people. Regarding this issue, the important role of
cerebral amyloid angiopathy in hypertensive ICHs of lobar
location has been demonstrated.27 However, the sample size
included in the present report may be underpowered to detect
some differences, and on the contrary, may exaggerate other
small disparities between the young and older patients.
Further studies are necessary to confirm our findings. Also, it
remains to be defined whether the length of exposure to
hypertension, the type of antihypertensive medication, and
the management of associated risk factors can influence ICH
location.
We could not find any correlation between hematoma size
and BP readings, and despite having a higher MAP, the
young had smaller hematomas and a lower rate of ventricular
extensions than did the older patients. These findings suggest
that the vascular disease and parenchymal degeneration
observed with the aging process are important factors that
may contribute to the more catastrophic effect of ICH in older
people.29 Our observations are in agreement with recent
evidence of the negative effect of aging on ICH-induced brain
injury.30,31 We hypothesize that the aging process may imply
changes in brain plasticity, diminishing the strength of the
brain tissue that normally acts as a restriction wall to the
extension of the hematoma. However, other factors can also
affect the volume and extension of ICHs. It has been shown
that some altered coagulation markers not routinely measured
in clinical practice are associated with the rapid expansion of
hypertensive hemorrhages.32
In summary, hypertensive ICH in the young differs in
several features from that of older patients, which in turn
suggests underlying distinctions in disease pathogenesis. Our
findings warrant further investigation on the influence of the
aging process in hypertensive ICH.
Disclosures
None.
References
1. Dennis MS, Burn JP, Sandercock PA, Barnford JM, Wade DT, Warlow
CP. Long-term survival after first-ever stroke: the Oxfordshire Com-
munity Stroke Project. Stroke. 1993;24:796–800.
2. Lavados PM, Sacks C, Prina L, Escobar A, Tossi C, Araya F, Feuerhake
W, Galvez M, Salinas R, Alvarez G. Incidence, 30-day case-fatality rate,
and prognosis of stroke in Iquique, Chile: a 2-year community-based
prospective study (PISCIS project). Lancet. 2005;365:2206–2215.
3. Brott T, Thalinger K, Hertzberg V. Hypertension as a risk factor for
spontaneous intracerebral hemorrhage. Stroke. 1986;17:1078–1083.
4. Thrift AG, McNeil JJ, Forbes A, Donnan GA. Three important subgroups
of hypertensive persons at greater risk of intracerebral hemorrhage.
Hypertension. 1998;31:1223–1229.
5. Feldmann E, Broderick JP, Kernan WN, Viscoli CM, Brass LM, Brott T,
Morgenstern LB, Wilterdink JL, Horwitz RI. Major risk factors for
intracerebral hemorrhage in the young are modifiable. Stroke. 2005;36:
1881–1885.
6. Jacobs BS, Boden-Albala B, Lin IF, Sacco RL. Stroke in the young in the
Northern Manhattan Stroke Study. Stroke. 2002;33:2789–2793.
7. Marini C, Totaro R, De Santis F, Ciancarelli I, Baldassarre M, Carolei A.
Stroke in young adults in the community-based L’Aquila registry:
incidence and prognosis. Stroke. 2001;32:52–56.
8. Bevan H. Sharma K. Stroke in young adults. Stroke. 1990;21:382–386.
9. Leno C. A prospective study of stroke in young adults in Cantabria,
Spain. Stroke. 1993;24:792–795.
10. Lin CL, Howng SL. Nontraumatic intracerebral hemorrhage in young
adult. Kaohsiung J Med Sci. 1997;13:237–242.
11. Ruiz-Sandoval JL, Cantu C, Barinagarrementeria F. Intracerebral hem-
orrhage in young people: analysis of risk factors, location, causes, and
prognosis. Stroke. 1999;30:537–541.
12. Del Brutto OH, Sanchez J, Campos X, Santos J, Mosquera A. Non-
traumatic intracerebral hemorrhage in young adults living in Guayaquil,
Ecuador (South America): analysis of 151 patients. Funct Neurol. 1999;
14:21–28.
13. Lai SL, Chen ST, Lee TH, Ro LS, Hsu SP. Spontaneous intracerebral
hemorrhage in young adults. Eur J Neurol. 2005;12:310–316.
14. Ruiz-Sandoval JL, Ortega-Alvarez L, Garcia-Navarro V, Romero-Vargas
S, Gonzalez-Cornejo S. Intracerebral hemorrhage in a referral hospital in
the central-western region of Mexico [in Spanish]. Rev Neurol. 2005;40:
656–660.
15. Barinagarrementeria F, Ruiz-Sandoval JL, Cantu C Hypertensive intra-
cerebral hemorrhage in young people. Neurology. 2001;56(suppl
3):A433. Abstract.
16. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL
Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; National
Heart, Lung, and Blood Institute Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure; National
High Blood Pressure Education Program Coordinating Committee. The
seventh report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.
JAMA. 2003;289:2560–2572.
17. Kothari RU, Brott T, Broderick JP. The ABCs of measuring intracerebral
hemorrhage volumes. Stroke. 1996;27:1304–1305.
18. Meaney E, Alva F, Moguel R, Meaney A, Alva J, Webel R. Formula and
nomogram for the sphygmomanometric calculation of the mean arterial
pressure. Heart. 2000;84:64.
19. Alfakih K, Walters K, Jones T, Ridgway J, Hall AS, Sivananthan M. New
gender-specific partition values for ECG criteria of left ventricular hy-
pertrophy: recalibration against cardiac MRI. Hypertension. 2004;44:
175–179.
ICH location in patients aged Յ40 years and
older persons.
Ruiz-Sandoval et al Hypertensive ICH in Young People 2949

6. 20. Jennett B, Bond M. Assessment of outcome after severe brain damage.
Lancet. 1975;1:480–484.
21. Aurell M. Screening for secondary hypertension. Curr Hypertens Rep.
1999;1:461.
22. O’Sullivan C, Duggan J, Lyons S, Thornton J, Lee M, O’Brien E.
Hypertensive target-organ damage in the very elderly. Hypertension.
2003;42:130–135.
23. Sadoshima S, Yoshida F, Ibayashi S, Shiokawa O, Fujishima M. Upper
limit of cerebral autoregulation during development of hypertension in
spontaneously hypertensive rats—effect of sympathetic denervation.
Stroke. 1985;16:477–481.
24. Salerno JA, Grady C, Mentis M, Gonzalez-Aviles A, Wagner E, Schapiro
MB, Rapoport SI. Brain metabolic function in older men with chronic
essential hypertension. J Gerontol A Biol Sci Med Sci. 1995;50:M147–M154.
25. Smeda JS. Cerebral vascular changes associated with hemorrhagic stroke
in hypertension. Can J Physiol Pharmacol. 1992;70:552–564.
26. Caplan LR. Hypertensive intracerebral hemorrhage. In: Kase CS, Caplan
LR, eds. Intracerebral Hemorrhage. Newton, Mass: Butterworth-
Heinemann; 1994:99–116.
27. Ritter MA, Droste DW, Hegedus K, Szepesi R, Nabavi DG, Csiba L,
Ringelstein EB. Role of cerebral amyloid angiopathy in intracerebral
hemorrhage in hypertensive patients. Neurology. 2005;64:1233–1237.
28. Meyer JS, Rogers RL, Mortel KF. Prospective analysis of long-term
control of mild hypertension on cerebral blood flow. Stroke. 1985;16:
985–990.
29. McCarron MO, Nicoll JA. Cerebral amyloid angiopathy and
thrombolysis-related intracerebral haemorrhage. Lancet Neurol. 2004;3:
484–492.
30. Gong Y, Hua Y, Keep RF, Hoff JT, Xi G. Intracerebral hemorrhage:
effects of aging on brain edema and neurological deficits. Stroke. 2004;
35:2571–2575.
31. Lee JC, Cho GS, Choi BO, Kim HC, Kim YS, Kim WK. Intracerebral
hemorrhage-induced brain injury is aggravated in senescence-accelerated
prone mice. Stroke. 2002;33:1190–1195.
32. Takahashi H, Urano T, Nagai N, Takada Y, Takada A. Progressive
expansion of hypertensive intracerebral hemorrhage by coagulopathy.
Am J Hematol. 1998;59:110–114.
2950 Stroke December 2006