M Nedergaard, L Klinken and O B Paulson

Secondary brain stem hemorrhage in stroke.

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Secondary Brain Stem Hemorrhage in Stroke
MAIKEN NEDERGAARD, B.M., LEIF KLINKEN, M.D., AND OLAF B. PAULSON, M.D.
SUMMARY The occurrence of secondary brain stem hemorrhage was studied in 435 autopsies from
patients with recent cerebral hemorrhage, infarction or ruptured cerebral aneurysms.
The frequency of secondary brain stem hemorrhage was found to be 45 % in cerebral hemorrhage, 15 % in
cerebral infarction, and 36% in ruptured aneurysms.
In the majority of cases the secondary brain stem hemorrhage occurred a few days after the onset of
cerebral hemorrhage or infarction. Ruptured aneurysms showed a more widespread temporal distribution
of secondary brain stem hemorrhage.
The median survival time was 2 days in cases of cerebral hemorrhage, 4 days in ruptured aneurysm and 4
days in cerebral infarction.
The frequency of secondary brain stem hemorrhage was significantly lower in patients younger than 20
years. No significant difference was found in its distribution between the sexes.
Secondary occipital lobe infarction was present in 3.5% of the patients. It is concluded that secondary
brain stem hemorrhage is a common major contribution to the cause of death in stroke.
Stroke, Vol 14, No 4, 1983
TRANSTENTORIAL HERNIATION is a well known
complication of expanding supratentorial lesions with
resulting clinical impairment of consciousness and
brain stem functions, and often culminating in death.
I_5
Expanding supratentorial lesions are frequently fol-
lowed by secondary brain stem hemorrhage.
6
The risk
of secondary brain stem hemorrhage has been regarded
as a function of the growth velocity of the primary
space occupying lesion, as well as of the volume which
the lesion ultimately achieves.
7,10
It is assumed that a
quickly expanding lesion, such as cerebral hemor-
rhage, will produce a more rapid caudal displacement
of the brain stem causing secondary brain stem hemor-
rhage, than a slower growing lesion such as infarction
with concomitant edema.
6
In early death following
acute cerebrovascular lesions, symptoms of cerebral
herniation are seen, and it is generally accepted that
herniation often is a significant factor contributing to
death. The aim of the present study was to evaluate
these aspects by the analysis of a large autopsy materi-
al with recent cerebral hemorrhage, infarction or rup-
tured aneurysm and to assess the lesions frequency,
time of occurrence, and age and sex distribution.
Material and Methods
Among all patients who had brain autopsy at Rigs-
hospitalet from January 1971 through August 1982,
435 had recent cerebral hemorrhage, infarction or rup-
tured aneurysm in the carotid artery distribution and
were selected for the present study. Patients who were
subjected to surgery were excluded from the study.
Only cases in which the death occurred within 100
days of onset of symptoms were considered. The
patho-anatomical diagnosis has been made by the same
neuropathologist (LK) in all cases. Spontaneous cere-
bral hemorrhage or infarction were clinically denned
as an event which was sudden in onset and unassociat-
From the Department of Neurology, Rigshospitalet, Copenhagen,
Denmark, and the Institute of Neuropathology, University of Copenha-
gen, Denmark.
Address correspondence to: Maiken Nedergaard, B.M., Institute of
Neuropathology, University of Copenhagen, 11 Frederik V's Vej, DK-
2100 Copenhagen O, Denmark.
Received December 1, 1982; revision accepted February 21, 1983.
ed with apparent trauma, neoplasm or vascular malfor-
mation.
The brains were fixed in formalin for at least 14 days
and selected areas were embedded in paraffin for mi-
croscopic examination. Sections from pons and mes-
encephalon were prepared in all cases.
Secondary brain stem hemorrhage was defined as
perivascular bleeding in pons or mesencephalon with-
out edema, glial proliferation or perivascular leucotyte
infiltration. Most bleedings were a few mm in size.
The intracranial vessels were carefully examined for
thrombosis. Unfotunately the extracranial arteries
were not routinely dissected in the general autopsy
department. The autopsy rate was 86-89%, and did not
differ according to age and sex.
The significance of difference was tested by a chi-
square test.
Results
Frequency of Secondary Brain Stem Hemorrhage
The frequency of secondary brain stem hemorrhage
varied considerably according to the character of the
precipitating supratentorial lesion (table 1). In cerebral
hemorrhage, the frequency was 45%, in ruptured con-
genital aneurysm 36%, and in cerebral infarction only
15%. However, the frequency of secondary brain stem
hemorrhage was 29% in those cases which showed
thrombosis and infarction in the internal carotid artery
and its branches. In cases of infarction without demon-
strated thrombosis in these vessels the frequency was
only 1.2%.
Length of Survival
Hemorrhage
The median survival time was 2 days (fig. 1). The
frequency of secondary brain stem hemorrhage was
significantly higher during the first 2 days than during
the following days (p = 0.0021). Complications of
either subarachnoidal bleeding or intraventricular
bleeding, or both, did not increase the risk of secon-
dary brain stem hemorrhage.
Ruptured Aneurysms
The median survival time was 4 days (fig. 2). Un-
like cerebral hemorrhage and infarction there was no
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502 STROKE VOL 14, No 4, JULY-AUGUST 1983
TABLE 1 Secondary Brain Stem Hemorrhage in Stroke
Frequency
No. with of secon-
secondary dary brain
No. of brain stem stem
cases hemorrhage hemorrhage
Cerebral hemorrhage 139 63 0.45
Ruptured congenital
aneurysm 134 48 0.36
Cerebral infarct,
all cases 162 24 0.15
Cerebral infarct with-
out thrombosis in the
internal carotid artery
system 82 1 0.01
Cerebral infarct with
thrombosis in the in-
ternal carotid artery
system 80 23 0.29
tendency towards an early secondary brain stem hem-
orrhage. The greater part of the ruptured aneurysms
were localised on the middle cerebral arteries but their
exact localisation did not affect frequency of the secon-
dary brain stem hemorrhage.
Infarction
The median survival time was 4 days (fig. 3). The
frequency of secondary brain stem hemorrhage was
significantly higher during the first 4 days than during
the following days (p = 0.0001). Up to day 30, the
Cerebral hemorrhage
Ruptured aneurysm
Number of cases
40- 1
m n a
i i i i
15 20 25 30
Survival in days
4
31-100
FIGURE 1. Frequency distribution of all deaths according to
numbers of days after cerebral hemorrhage. Striped areas rep-
resent the finding of secondary brain stem hemorrhage.
Number of cases
40-
35
30-L
25-
20
15-1
10
5- d
VVt
5
t
10
m
mM
pjfl A i // n
25 30 31-100 15 20
Survival in days
FIGURE 2. Frequency distribution of all deaths according to
numbers of days after ruptured aneurysm. Striped areas repre-
sent the finding of secondary brain stem hemorrhage.
survival time in cases of infarction with demonstrated
thrombosis in the intracranial vessels was identical
with the distribution in those without thrombosis.
After day 31, there was a higher frequency of death in
cases of infarction without demonstrated thrombosis
(fig. 3).
Relation Between Secondary Brain Stem
Hemorrhage, Sex and Age
Table 2 shows a slight tendency towards a higher
frequency of secondary brain stem hemorrhage in
women, a difference which is statistically non-signifi-
cant.
No instances of secondary brain stem hemorrhage
were encountered in 11 patients who were younger
than 20 years (table 3). In all other age groups secon-
dary brain stem hemorrhage occurred with the same
frequency, although there was a tendency to a some-
what higher frequency in the age groups between 40
and 70 years. The difference between the patients un-
der 20 years and those belonging to other age groups
was statistically significant (p = 0.042).
Secondary Occipital Infarcts
Secondary occipital infarcts were found in 15 pa-
tients (3, 5%) who died relatively late (table 4). Six
had cerebral hemorrhage, 7 had ruptured aneurysm,
and only 2 had cerebral infarction. No correlation was
found between occipital lobe infarction and secondary
brain hemorrhage.
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SECONDARY BRAIN STEM HEMORRHAGE IN STROKE/Nedergaard et al. 503
Cerebral infarction without
intracranial thrombosis
TABLE 3 Age Distribution of Secondary Brain Stem Hemorrhage
r
20-
15-
10-
5-
vlumber o cases
2.I.: ..ZltHnJ.
lfln
Cerebral infarction with
intracranial thrombosis
10-
- f e l
LiiiiL
T B M
i 1 r
10 15 20
Survival in days
11 m n
25
-9-
//-
m
30 31-100
FIGURE 3. Distribution of all deaths according to number of
days after cerebral infarction. Striped areas represent secon-
dary brain stem hemorrhage.
Discussion
Supratentorial space occupying lesions may cause
transtentorial caudal herniation with downward dis-
placement through the tentorial notch of parts of the
hemispheres, which compress the diencephalon and
the adjoining midbrain.
2
Neuropathological examina-
tion of such cases shows cerebral grooving in the vicin-
ity of the tentorial notch resulting from compression
against the free edge of the tentorium cerebelli.
However, grooves are often found in the uncus of
Cerebral hemorrhage
0-19
20-39
40-59
60-79
80-99
Total
Ruptured aneurysm
0-19
20-39
40-59
60-79
80-99
Total
Cerebral infarction
0-19
20-39
40-59
60-79
80-99
Total
No. of
cases
3
10
45
58
23
139
8
20
76
39
1
134
0
2
29
71
52
162
No. with
secondary
brain stem
hemorrhage
0
3
23
28
9
63
0
8
30
10
0
48
0
0
6
12
6
24
Frequency
of secon-
dary brain
stem
hemorrhage
0
0.33
0.51
0.48
0.39
0.45
0
0.35
0.40
0.26
0
0.36
0
0
0.21
0.17
0.12
0.15
brains free from overt disease," and the range of nor-
mal variation is not defined." Secondary brain stem
hemorrhage always represents a pathological condi-
tion, indicating advanced transtentorial herniation, but
some degree of transtentorial herniation may be pres-
ent without the occurrence of such hemorrhage as indi-
TABLE 4 Occipital Lobe Infarction Secondary to Transtentorial
Caudal Herniation
TABLE 2 Sex Distribution
Cerebral hemorrhage
women
men
total
Ruptured aneurysm
women
men
total
Cerebral infarction
women
men
total
of Secondary Brain Stem
No. with
No. of
cases
66
73
139
52
82
134
79
83
162
secondary
brain stem
Hemorrhage
Frequency
of secon-
dary brain
stem
hemorrhage hemorrhage
33
30
63
21
27
48
13
11
24
0.50
0.41
0.45
0.41
0.33
0.36
0.17
0.13
0.15
Survival for
patients with
secondary brain
stem hemorrhage
Survival for
patients without
secondary brain
stem hemorrhage
Cerebral
hemorrhage
N = 6
2 days
3
10 days
6 days
12
13 days
Ruptured
aneurysm
N = 7
2 days
4
9
10
15
15 days
13 days
Cerebral
infarction
N = 2
12 days
20 days
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504 STROKE VOL 14, No 4, JULY- AUGUST 1983
cated by our own cases with secondary occipital lobe
infarction without brain stem hemorrhage.
It has been postulated that either the displacement of
the brain tissue per se,
2< ll_l3
'
15
occlusion of veins at the
level of the tentorial notch,
4
'
15,16
or lengthening and
angulation of the penetrating arteries caused by caudal
displacement of the brain stem,
17,18
are the reasons for
the appearance of secondary brain stem hemorrhages.
It is contended that secondary brain stem hemorrhage
occurs only in the presence of active circulation in the
damaged blood vessels of the displaced rostral brain
stem."
There is some variation in the incidence of secon-
dary brain stem hemorrhage reported by different au-
thors. Our finding that 45% of the patients with lethal
cerebral hemorrhages had secondary brain stem hem-
orrhage, is comparable to 57% reported by Cohen,
6
but
higher than the frequency of 14% and 31 % reported by
Poppen
15
and Klintworth,
19
respectively.
Most patients died within 48 hours, which may indi-
cate that in hemorrhage it is the expanding lesion and
not reactive edema which is the primary cause of sec-
ondary brain stem hemorrhage.
In cases of ruptured aneurysm a frequency of 36% of
secondary brain stem hemorrhages was found, which
is a higher value than the frequency of 21 % reported by
Cohen.
6
Secondary brain stem hemorrhage was ob-
served with equal frequency in early and late death in
patients with ruptured aneurysm. Most patients died
shortly after either the acute episode or after a rebleed-
ing from the aneurysm.
The frequency of secondary brain stem hemorrhage
in cases of infarction was 15%, which is comparable to
9% reported by Cohen
6
and 11.6% reported by
Klintworth.
19
The finding that secondary brain stem
hemorrhage had the highest frequency from day 1 to 5,
with the maximum at day 4, is consistent with the
prevailing clinical concept
20,21
and recent CT find-
ings
22
indicating that cerebral edema becomes maximal
at 2 to 7 days after infarction. Our results do not con-
firm results of Bounds,
23
who found that in 100 cases
of recent cerebral infarction 31% of the deaths were
caused by transtentorial herniation with maximum at 1
to 2 days. The neuropathology of transtentorial herni-
ation was, however, not described in their study.
The great difference observed in the present study
between cases of secondary brain stem hemorrhage in
cerebral infarction with thrombosis in comparison with
those without thrombosis, can only partly be ex-
plained. As the extracranial arteries were not routinely
dissected we have undoubtedly missed some of the
thrombosis. The time of death after the acute attack in
cases with demonstrated intracranial thrombosis ver-
sus those without is broadly similar and it can hardly
explain the difference.
Impaired general circulation, including circulation
within the brain stem, precluding development of sec-
ondary brain stem hemorrhages in cases of infarction
without thrombosis in the cerebral vessels might con-
tribute to the difference, but in this material we have no
evidence of such impairment of the general circula-
tion.
A possible explanation might be that the acute lesion
has been larger in patients with proven arterial occlu-
sion resulting in the development of more marked ede-
ma and thus in a "larger space occupying lesion" and
more pronounced transtentorial caudal herniation.
Sex-related differences in the occurrence of secon-
dary brain stem hemorrhages are a debated matter.
Some authors reported higher frequency in men
4,7> 24
and one author in women.
6
The present study does not
demonstrate a significant difference between the two
sexes. Our results indicate paucity of secondary brain
stem hemorrhage in very young persons, a finding
which is in agreement with earlier investigations
6,7
-
25
The diminished frequency of secondary brain stem
hemorrhages in young persons may be caused by a
higher elasticity of the tissues. The tendency towards
slightly decreased frequency of secondary brain stem
hemorrhage in the very elderly (not significant) may be
caused by cerebral tissue atrophy resulting in increased
extracerebral space.
Occipital lobe infarction is a well defined pathologi-
cal entity,
25,26
secondary to increased supratentorial
pressure. The condition results from a displacement of
the posterior cerebral artery and the hippocampal gyrus
through the tentorial notch following stretching and
compression of the cortical branches of that artery
against the tentorial edge.
24
The observed frequency
(3.5%) of such cases is surprisingly high and has not
been reported previously. No correlation was found
between occipital lobe infarction and secondary brain
stem hemorrhage. The main finding of the present
study was that secondary brain stem hemorrhages were
frequent in all three groups investigated. They are
strongly correlated to transtentorial herniation and in-
dicate major disturbances of the brain stem. It can be
assumed that they have contributed significantly to the
death of the patients. The present material does not
allow to draw conclusions on differences in the cause
of death among patients with and without secondary
brain stem hemorrhage.
References
1. Johnson RT, Yates PO: Clinicopathological aspects of pressure
changes at the tentorium. Acta Radiol 46: 242-249, 1956
2. Scheinker IM: Transtentorial herniation of the brain stem: A char-
acteristic clinicopathologic syndrome: Pathogenesis of hemor-
rhages in brain stem. Arch Neurol Psychiat 53: 289-298, 1945
3. Schwarz GA, Rosner AA: Displacement and herniation of the
hippocampal gyrus through the incisura tentorii. Arch Neurol Psy-
chiat 46: 297-321
4. Cannon BW: Acute vascular lesions of the brain stem. Arch Neurol
Psychiat 66: 687-696, 1951
5. Plum F, Posner JB: The diagnosis of stupor and coma. F. A. Davis
Company, Philadelphia, 1982
6. Cohen SI, Aronson SM: Secondary brain stem hemorrhages. Arch
Neurol 19: 257-263, 1968
7. Attwater HL: Pontine hemorrhages. Guy Hosp Rep 65: 339-389,
1911
8. Fields WS, Halpert B: Pontine hemorrhages in intracranial hyper-
tension. Am J Pathol 29: 677-687, 1953
9. Lindenberg R: Compression of brain arteries as pathogenetic factor
for tissue necroses and their areas of predilection. J Neuropath Exp
Neurol 14: 223-243, 1955
10. Wolman L: Ischaemic lesions in the brain stem associated with
raised supratentorial pressure. Brain 76: 364-377, 1955
11. Klintworth KG: Paratentorial grooving of human brains with par-
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SECONDARY BRAIN STEM HEMORRHAGE IN STROKE/Nedergaard et al. 505
ticular reference to transtentorial herniation and the pathogenesis of
secondary brain-stem hemorrhages. Am J Pathol S3: 391-399,
1968
12. Vincent C, David M, Thiebaut F: Le cone de pression temporal
dans les tumeurs des hemispheres cerebraux. Sa symptomatolofie,
sa gravite, les traitement qu'il convient du lui opposer. Rev Neurol
(Paris) 65: 536-545, 1936
13. Van Gehuchten P: Le mechanisme de la mort dans certains cas de
tumeur cerSbrale. Encephale 2: 113-127, 1937
14. Jefferson G: Tentorial pressure cone. Arch Neurol Psychiat (Chica-
go) 40: 857-876, 1938
15. Poppen JL, Kendrick JFJR, Hicks SF: Brain stem hemorrhages
secondary to supratentorial space-taking lesions. J Neuropath Exp
Neurol 11: 267-279, 1952
16. Evans JP, Scheinker IM: Histologic studies of the brain following
head trauma. Arch Neurol Psychiat (Chicago) 50: 258-278, 1943
17. Blackwood W, Corsellis JAN. Greenfield's Neuropathology. 3rd
ed. London, Arnold, 1976, 121-124
18. Johnson RT, Yates PO: Brain stem haemorrhages in expanding
supratentorial conditions. Acta Radiol (Stockholm) 46: 250-256,
HEMIPARESIS OR HEMIPLEGIA without sensory,
visual or speech deficit (Pure motor hemiparesis,
PMH) is the classical presentation for lacunar infarc-
tion in the internal capsule or basis pontis.
1
Other re-
ported causes of this clinical syndrome include: in-
farcts or cortical,
2
pyramidal
1,3
'
4
or midbrain
5
location,
metastases,
23
multiple sclerosis,
2
nocardial abscess,
6
post-craniotomy hemorrhage,
7
and hemorrhages in the
basis pontis
8
or internal capsule.
2
'
910
PMH has not
been described in the setting of primary hypertensive
putaminal hemorrhage.
11
-
12
This report documents, by
detailed neurological evaluation in the acute stage, an
instance of a syndrome of PMH in putaminal hem-
orrhage.
Case Report
A 44 year old left-handed hypertensive male noticed
right arm weakness and slurred speech after awakening
on 8/8/82. He had no headache, nausea, vomiting or
gait difficulties. Over the following 2 to 3 hours the
right arm paresis worsened and a mild weakness of the
From the Department of Neurology, University of South Alabama
College of Medicine, Mobile, Alabama.
Address correspondence to: Carlos S. Kase, M.D., Department of
Neurology, University of South Alabama, 2451 Fillingim Street, Mo-
bile, Alabama 36617.
Received September 21, 1982: revision accepted December 20,
1982.
1956
19. Klinthworth GK: Evaluation of the role of neurosurgical procedure
in the pathogenesis of secondary brain stem haemorrhage. J Neurol
Neurosurg Psychiat 29: 423-425, 1966
20. Shaw C-M, Alvard EC Jr, Berry RG: Swelling of the brain follow-
ing ischemic infarction with arterial occlusion. Arch Neurol 1:
161-177, 1959
21. Berry RG, Alpers BJ: Occlusion of the carotid circulation: Patho-
logic considerations. Neurology (NY) 7: 223-237, 1957
22. Terent A et al.: Ischemic edema in stroke. Stroke 12: 33-39, 1981
23. Bounds JV et al: Mechanisms and timing of deaths from cerebral
infarction. Stroke 12: 474-477, 1981
24. Finney LA, Walker AF: Transtentorial herniation. Springfield 111.,
Charles C Thomas, 1962
25. Sutherland S: The tentorial notch and complications produced by
herniations of the brain through that aperture. Brit J Surg 45: 422-
438, 1958
26. Moore M, Stern K: Vascular lesions in the brain stem and occipital
lobe occurring in association with brain tumors. Brain 61: 70-98,
1938
right leg developed. When examined 4 hours after the
onset, he was alert, oriented, and gave an accurate
description of the events leading to admission. His
speech was dysarthric but free of dysphasia. The blood
pressure was 220/130. Motor examination showed a
moderate paresis of shoulder abduction and elbow
flexion, with minimal weakness of distal movements.
The lower extremity had slight paresis of foot dorsi-
flexion, with intact proximal strength. The deep ten-
don reflexes were slightly hyperactive in the right arm,
and plantar reflexes were flexor. Coordination was
intact bilaterally.
Sensation was intact for touch and pin-prick in
limbs, trunk and face. The slightest stimulation of indi-
vidual hairs on the right limbs was felt normally and
symmetrically. He did not extinguish to double simul-
taneous tactile stimulation. Joint position and vibra-
tory sense were intact. Stereognosis, barognosis and
graphesthesia were normal and symmetric.
Cranial nerve testing showed a marked right inferior
facial palsy. Otherwise the examination showed full
visual fields to single and double simultaneous stimuli,
normal extraocular movements without gaze prefer-
ence or nystagmus, reactive pupils of 2 mm diameter,
intact facial sensation, preserved palate and tongue
movements, and absence of bucco-lingual dyspraxia.
CT scan on admission showed a small area of high
attenuation (96 Hounsfield units) at the level of the left
Hypertensive Putaminal Hemorrhage Presenting as
Pure Motor Hemiparesis
JORGE F. TAPIA, M.D., CARLOS S. KASE, M.D., RICHARD H. SAWYER, M.D.
AND J. P. MOHR, M.D.
SUMMARY A 44 year old hypertensive man presented with a pure motor hemiparesis, and CT scan
showed a putaminal hemorrhage. The clinical course was characterized by rapid resolution of the deficits.
This case illustrates a variety of putaminal hemorrhage of good functional and vital prognosis, and stresses
the value of CT scanning as a tool for diagnosis and prognosis.
Stroke, Vol 14, No 4, 1983
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