Spontaneous Severe

Intracerebral

Angiospasm

Hemorrhage

Following

Ruptured

—A Pathological

Toshisuke

SAKAKI, Toru

Hiroyuki

KONISHI*

Aneurysm

Study—

TSUNODA,

HOSHIDA,

Noboru Departments

Shigeru

in Cases of

Tetsuya

MORIMOTO,

HASHIMOTO,

and

Yoshio

HIASA*

of Neurosurgery and *Second Division of Pathology, Nara Medical University, Kashihara, Nara

Abstract Eleven

patients

developed In all cases, tients,

tion

the

hematoma compared

even

or severe

hemorrhage

occurred

in the ipsilateral

was

surgically

to those

after

changes

though

most

were

suffered

ment

of intracerebral

patients

severe

hemorrhage

intracerebral

and

hypertensive

cerebral than

hemorrhage,

the

young

and

angiospasm those

without

angiospasm,

perforating

showed

the

lamina have

prior

aneurysm.

The

risk

surgery. In nine pa

were

resected

to be of

findings

the

for

unusually

histological

media

These

a higher

aneurysm

aneurysm

arteries

and

normotensive.

cerebral

after

hematomas

hemorrhage.

elastic may

ruptured

111 months to the original

bleeding scans

intracerebral in

following

31 and

hemisphere

tomographic

degenerative

who have

angiospasm between

evacuated

Computed

various

tients

Key words:

of moderate

intracerebral

examination.

showed

arteries,

a history

hemorrhage

histological extended

with

spontaneous

examina perforating

suggest

for subsequent

that

pa

develop

angiospasm.

perforating

artery,

ruptured

aneurysm

had undergone surgery for ruptured aneurysm (31 111 months before). Angiography had clearly dem Morphological changes of the cerebral vessels associ onstrated severe angiospasm, despite which they ated with subarachnoid hemorrhage (SAH) or had recovered and were discharged with (4 cases) or angiospasm have been demonstrated in necropsy without (7 cases) neurological sequelae (Table 1). material, 1,9,14,18,23,24) and animal experiments. 10,17,25,26) Outpatient follow-up included routine evaluation of neurological status and blood pressure. Previous These reports mainly examined the affected cerebral computed tomographic (CT) scans had shown a arterial trunk identified by angiography. Any mor focal low-density area (of varying sizes) in the phological changes in the branching perforating hemisphere affected by angiospasm in seven cases. arteries were not reported and previously regarded as No abnormality was found in the other four cases. unimportant. CT scans on this admission showed the hematoma We thus investigated morphological changes in mainly coincided with these low-density areas. The the perforating arteries as a cause of intracerebral hematoma was irregular and atypical of hypertensive hematoma (ICH) in patients with a history of aneu ICH. Three cases (Cases 3, 6, and 7) had been rysm surgery and severe angiospasm. diagnosed as mild hypertensives, and were receiving antihypertensive drugs. The other eight cases were Materials and Methods normotensive and had no medication. The ICH was evacuated surgically in nine cases Eleven patients presented with ICH. Their ages because of uncal herniation sign. The ICH always in ranged from 56 to 66 years (mean 60.1 years). All cluded a coagulated lump in the center which was Received May 14, 1990; Accepted January 7, 1991 much harder than the remainder. The hard coagula Introduction

Table

1

Summary

of cases

with

ICH

after

severe

angiospasm

usually surrounded a bleeding perforating artery, which was removed. The excised artery was exam ined histologically with hematoxylin-eosin (HE), Azan-Mallory, and van Gieson staining. Illustrative

Cases

Case 1: A 57-year-old female suffered a sudden onset of severe headache and became unconscious for a while on March 12, 1986. A CT scan demonstrated SAH. Angiography showed an aneurysm at the right internal carotid artery-posterior communicating artery junction. The aneurysmal neck was clipped through the right pterional approach on the same day. Two weeks after the surgery, she became lethar gic and developed left hemiparesis. Right carotid angiography demonstrated severe angiospasm of the right carotid arterial branches. Her neurological condition improved with hypervolemic hypertensive treatment. She was discharged with almost no neurological deficit, although CT scans showed a low-density area in the right frontal lobe. Follow-up CT scans were performed and there was no changes 2 months before this admission (Fig. IA). She was normotensive whenever examined. On April 11, 1989, she became unconscious and suffered left hemiparesis. Soon after, she was read mitted. CT scans showed a large ICH extending from the right putamen to the frontal lobe (Fig. 1B). Subse quent angiography demonstrated that the aneurysm was well clipped. The hematoma was evacuated and a bleeding perforating artery was discovered in a hard coagula lump. The bleeding perforating artery was removed. Histological examination showed degenerative changes of the media and dysruption of

secondary

to SAH

the internal elastic lamina. Postoperatively, she regained consciousness but moderate left hemiparesis persisted. CT scans re vealed a new low-density area in the putamen (Fig. 1Q. She remains hemiparetic despite rehabilitation therapy. Case 5: A 65-year-old male suffered a SAH caused by rupture of an anterior communicating artery aneu rysm on April 16, 1984. The aneurysmal neck was clipped through the right pterional approach. Ten days later, left hemiparesis occurred. Right carotid angiography demonstrated severe angiospasm of the right carotid arterial branches. He underwent hyper volemia for the spasm and a ventriculoperitoneal shunt for hydrocephalus. He was discharged with very slight left hemiparesis. His blood pressure was normal and CT scans demonstrated no abnormality in the brain parenchyma in December, 1987 (Fig. 2A). On June 17, 1988, he was readmitted complaining of a left hemiparesis. CT scans showed a hematoma localized in the right thalamus (Fig. 2B). With hemostatics and steroids his neurological deficit im proved remarkably 7 days after the readmission. He returned to his occupation 2 months later in spite of persistent left hemiparesis. Results Most resected perforating arteries had a similar microscopic appearance, with occasional variations. The arteries generally dilated (Fig. 3). For a short distance from the parent vessel, the intima showed slight subendothelial fibrous thickening, presumably continuous from the parent vessel. However, no

Fig.

I

Serial CT

precontrast scans

mission, the

scans

a slight

frontal

region.

admission

showing margin

in

2 months

showing

right

irregular

CT

obtained

a

Case

before

1.

low-density B:

large

extending

A:

this

ad

area

CT

scans

in on

hematoma

with

from

right

the

putamen to the right frontal lobe. C: CT scans obtained after the hematoma evacuation, showing a distinct to the hematoma.

Fig.

2

Case

5.

brain right

parenchyma. thalamus.

A:

Precontrast

CT

scans

B: Precontrast

6 months CT

hyaline degeneration of the intima, as seen for exam ple in hypertensive angiopathy, was observed in these portions. Distally also intimal thickening was never seen. The elastic lamina was clearly identified by elastin staining. It was occasionally frayed and reduplicated (Fig. 4), but usually was morphologically normal. The smooth muscle of the media, appearing red by Azan-Mallory staining, was essentially invariably replaced by degenerative tissue (Fig. 3A). Degenerative changes of the media were mainly fibrinoid changes using the usual fibrin stain and HE

scans

before

this

on

admission

admission

low-density

showing

demonstrating

no

area

secondary

abnormality

a hematoma

in in the

stain (Fig. 3). Vacuolation in the media was also ob served in many arteries (Fig. 5). These fibrinoid changes often involved much of the wall proximal to the parent artery, but occasionally extended distally. The adventitia showed little change apart from a slight increase in connective tissue and hemosiderin deposits. It appeared similar to and continuous with the corresponding layer of the parent vessel. Discussion This

study

shows

that

some

parts

of

perforating

Fig. 3

Fig. 4

Histological appearance of the media of the cerebral perforating artery in Case 1. A: The media is replaced with thin and fibrous tissues (arrows). Azan-Mallory stain, x 200. B: Arteries are dilated maximally and the media is very thin (arrows). HE stain, x 100.

Histological features of the elastic lamina of perforating artery in Case 11. The elastic lamina is frayed (arrows) (A) and duplicated (arrow heads) (B) in many parts from the proximal to distal portions. Elastica-van Gieson stain, x 200 (A) and x 400 (B) .

arteries demonstrate pathological those in the main arterial trunk

changes similar to in angiospasm. The

pathological changes were most remarkable in the media. Notably, the small arteries lost tone and dilated because of this media degeneration. The subendothelial proliferation frequently observed in angiospastic main arterial trunks in the chronic stage',","' was seldom shown in the distal per forating artery. Elderly hypertensive patients demonstrate various changes in the walls of perforating arteries. 5,6,11,12,21 The most common finding is hyaline thickening of flip ;nt;mn inrl fihr;nr~i ra nt+rricic ~~ rho mo 1; .,n

Fig. 5

The media of the perforating arteries in Case 2 showing various degenerative changes, thin ning, vacuolation (arrowheads), fibrous necro sis (arrow), etc. Azan-Mallory stain, x 100 (A) and x 400 (B).

result of arteriosclerosis.b,','z,z',z') Patients with hypertensive ICH demonstrate miliary aneurysms sec ondary to fibrinoid necrosis of the perforating arterial wall characterized by lipohyalinosis.''2',27) Cole and Yates') found miliary aneurysms in 46% of hypertensives, but only in 7% of normotensives. Such aneurysms occurred in 90% of hypertensives with massive hemorrhage and in all with small slit hemorrhage. The incidence of aneurysms is age dependent, reaching 71 % in 65 to 69-year-old hypertensives, but only two of 21 hypertensives under 50 had aneurysms. Normotensives with aneurysms were all over 65 years. These observations suggest that if the hematomas of our cases were sec ondary to age-dependent hypertensive angiopathy, histological examination of the basal ganglia would find miliary aneurysms with lipohyalinosis in the per forating arteries. However, our study disclosed no lipohyalinosis, although thinning and fibrinoid necrosis of the whole media were found. Of the 11 pa tients, eight were normotensive and six were under 60-years-old. Therefore, we believe the changes in the media were secondary to the angiospasm of the parent arteries or the perforating arteries themselves. Such pathological changes may indicate that the per forating arteries are much weaker than normal, like arterioles in hypertensive angiopathy. In cerebral tissue with infarction, the incidence of cerebral hemorrhage may be high. Many reports2,'6,'9,22>suggest the onset of ICH secondary to cerebral infarction occurs during blood-brain barrier disruption which is initiated within 7 days of infarc tion, and continues for about 4 weeks. Cases with recanalization of occluded artery have a high in cidence of hemorrhagic infarction. 15)Recent cerebral

infarction is also a factor in ICH after surgery for carotid stenosis.3.a,"3> In our study, the hemorrhage was unlikely to be secondary to cerebral infarction following angiospasm after SAH, since ICH occur red 31-111 months after SAH, and the cerebral in farction was in the cicatrix stage in which abnormal ly increased permeability of cerebral vessels is never observed.1,20) Our findings suggest that patients developing severe angiospasm due to SAH may be at greater risk of further spontaneous ICH than those without previous

severe

angiospasm.

14)

15)

16)

17)

References 1)

2)

3)

4)

5)

6)

7)

8)

9)

10)

11)

12) 13)

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hemor hemor

Address reprint requests to: T. Sakaki, M.D., Department of Neurosurgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634, Japan.