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Symmetric Brainstem Necrosis in an Adult Following
Hypotension: An Arterial End-Zone Infarct?
J. CRAIG JURGENSEN,
M . D . , * JAVAD TOWFIGHI, M . D . , t ROBERT W . B R E N N A N , M . D . , *
AND WILLIAM H. JEFFREYS,
M.D.
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SUMMARY A 44-year-old woman with prolonged coma and hypotension following drug overdosage
developed bilateral hemorrhagic infarcts in the dorsolateral brainstem. The regional distribution of these
paired lesions corresponds to the area of confluence of penetrating arteries in the brainstem. It is suggested
that under exceptional circumstances brainstem arterial end-zones may be vulnerable to anoxic-ischemic
insult.
Stroke Vol 14, No 6, 1983
T H E S T R U C T U R A L ALTERATIONS of cerebrum
and cerebellum following anoxia-ischemia have been
studied extensively in man and in experimental ani­
mals.
Selective vulnerability of particular regions
within the cerebrum and cerebellum has been attribut­
ed in part to vascular anatomic factors such as arterial
boundary or end-zone distributions. In contrast, stud­
ies of the topography of anoxic-ischemic involvement
in the brainstem suggest that lesions are topistic; i.e.,
selective for specific neuronal structures. ^ This pat­
tern of selective vulnerability in brainstem has been
attributed to metabolic factors such as the higher blood
flow and metabolic requirements of these nuclei and
their high level of lactic acid content during anoxia."
The influence of vascular anatomic factors in the distri­
bution of anoxic-ischemic lesions in brainstem has
been given little attention.
A patient with bilateral symmetric columnar necro­
sis of the brainstem associated with prolonged hypo­
tension is reported. Evidence implicating vascular ana­
tomic factors in the pathogenesis of these brainstem
lesions is reviewed.
1 - 5
5
9
10
Case Report
A 44-year-old woman was found unresponsive at
her home. Her blood pressure was unobtainable and
respirations were irregular and shallow. She had a past
history of epilepsy and had been under treatment with
phenytoin 300 mg and phenobarbital 45 mg daily for
From the *Department of Medicine (Neurology), and the tDepartment of Pathology (Anatomic Pathology), M.S. Hershey Medical Cen­
ter, Hershey, Pennsylvania 17033.
Address correspondence to: Robert Brennan, M . D . , Department of
Medicine (Neurology) M.S. Hershey Medical Center, Hershey, Penn­
sylvania 17033.
Received May 6, 1982; revision accepted May 24, 1983.
many years through her family physician. She had also
taken chlorpromazine 75 mg daily for a chronic schi­
zophreniform illness. From the circumstances of her
discovery, and the clinical observation of early gan­
grene in one upper extremity it was deduced that she
had lain unresponsive for many hours, possibly several
days in all. On arrival to a local Emergency Room,
treatment for presumed drug overdose was instituted
including endotracheal intubation and assisted ventila­
tion. Physical examination revealed a brachial blood
pressure of 60/40 mm Hg, pulse rate 32 per minute,
rectal temperature 29°C. She was unresponsive to
sound, or painful stimulation. There was a superficial
pressure sore on the left hip, and gangrene of the left
hand. She had spontaneous, nonrhythmic eyelid blink­
ing, random and conjugate roving eye movements lat­
erally, and pupils which were equal, mid-position,
round and unreactive bilaterally. Corneal stimulation
elicited reflex blinking. The neck was supple. Extrem­
ities were flaccid to passive movements and all deep
tendon reflexes were absent. Plantar responses were
unelicitable. Toxicology studies demonstrated the
presence of chlorpromazine and phenytoin in thera­
peutic levels, and phenobarbital at a toxic level (72 fJLg/
ml). Other laboratory abnormalities on admission in­
cluded a glucose of 560 mg/dl, B U N 42 units, Creati­
nine 3.4 mg/dl, Creatine phosphokinase 2288 units.
The platelet count was reduced to 86000/mm , the PTT
was 77 s e c , and PT 19.7 s e c , consistent with a con­
sumption coagulopathy. A cerebral CT scan was with­
in normal limits. Despite aggressive treatment with
intravenous fluids and Dopamine, and correction of
hypothermia, she remained hypotensive for the first
three days of hospitalization. With institution of hemo­
dialysis, the barbiturate level fell to 22 ju,g/ml, with no
significant improvement in her condition. She re3
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gyrus, and just lateral to the left lateral geniculate
body. In addition to the above, a well-defined round
nodule of about 1 cm was present in the left middle
temporal gyrus. Intracranial cerebral arteries including
the vertebrobasilar system had a minimal atherosclero­
sis and were patent. The circle of Willis was complete
and roughly symmetric. The spinal cord was not exam­
ined.
Microscopic examination of the hemorrhagic le­
sions disclosed necrosis, containing eosinophilic neu­
rons, axonal spherules, macrophages and reactive as­
trocytes. This was consistent with a one- to two-week
old infarct. A more recent hemorrhage was noted in the
periphery of the necrotic areas (figs. 4 and 5). The
necrotic columns in pons included the region of the
sensory nuclei and tracts of trigeminal nerves as well
as their motor nuclei. In medulla the region of cuneate
nuclei and fasciculi, nuclei and spinal tracts of the
trigeminal, solitary nuclei and tracts, and a portion of
the internal arcuate fibers were involved. The cerebel­
lum revealed a modest, diffuse loss of Purkinje cells
and Bergmann gliosis. The left temporal lobe nodule
proved to be a ganglioglioma. No evidence of conven­
tional boundary zone infarction or of diffuse hypoxic
changes were found in cerebral cortex or hippocampi.
Basal ganglia and thalami were normal. Brainstem
nuclei not included in the infarcts were unaffected ex­
cept for the inferior colliculi which showed partial
neuronal loss and astrocytosis.
FIGURE 1 .
areas
Cross-sections
of hemorrhage
from
in lateral
pons
pontine
showing
symmetric-
tegmentum.
mained unresponsive to pain, with flaccid extremities.
Corneal reflexes persisted, and pupillary light reflexes
returned. An EEG demonstrated generalized low volt­
age activity. On the 11th hospital day she developed
intermittent generalized seizures, a temperature of
38.5°C, and clinical and radiographic evidence of
pneumonia. She expired on the 11th hospital day, in
the setting of sudden bradycardia and irreversible
shock.
Post-Mortem Examination
General pathology findings included a severe necro­
tizing tracheitis, bilateral bronchopneumonia, and
ischemic enterocolitis. The most significant neuro­
pathologic findings were large, well-defined, bilateral,
symmetric areas of hemorrhagic necrosis in the dorso­
lateral aspects of the brainstem (figs. 1 and 2) and
claustrum (fig. 3). In the brainstem, the lesions ap­
peared as two axial columns or cylinders, extending
continuously from the lower segment of the pons to the
caudal part of the medulla. Their largest diameter (0.6
cm) was in the medulla and they appeared to join
caudally (fig. 2). Three other hemorrhagic but asym­
metrically located lesions of about 0.5 cm were found
in the right inferior parietal gyrus, left middle frontal
FIGURE 2.
metric
Cross-sections
hemorrhages.
of medulla
showing
bilateral
sym­
H Y P O T E N S I V E B R A I N S T E M WFARCTS/Jurgensen
F I G U R E 5.
Medulla,
homogenization
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FIGURE 3 .
Coronal
hemorrhage
in
section,
frontal
lobe. Bilateral
symmetric
claustrum.
Discussion
The significance of this case lies in the most unusual
distribution of cerebral lesions in this hypotensive,
hypothermic patient, i.e. bilateral columnar necrosis
of brainstem. Review of clinical and experimental ma­
terial dealing with global cerebral hypoxia due to car­
diac arrest or hypotension indicates that the most vul­
nerable neural structures in adults are cerebral and
cerebellar cortices. The pathology may be in the form
of selective neuronal loss, in the form of boundaryzone infarcts or as a combination of the two proc­
esses. "'' " In children and young adults, and in experi­
mental animals, deep cerebral structures and brainstem
may be involved a l s o . Occasionally, the impact
of anoxic-ischemic necrosis has been virtually restrict­
ed to brainstem, thalamic nuclei and spinal
c o r d . - - - - The brainstem structures most suscept1
5-9
6
12
l3
l5
11-14
16
el al
margin
necrosis
rated from
normal
(H & E,
X125).
tissue
969
of a necrotic
with axonal
lesion.
spherules
(left) by a hemorrhagic
The area of
(right)
is sepa­
zone
(center)
ible to anoxic-ischemic injury in humans include: infe­
rior colliculi, inferior and superior olives, oculomotor
nuclei, vestibular nuclei, nucleus solitarius, trigeminal
nuclei, nucleus ambiguus, reticular zone of the sub­
stantia nigra, brainstem reticular formation, pontine
nuclei, and nucleus cuneatus and gracilis. The vulner­
ability of these particular structures to anoxia has been
attributed to various factors including peculiarities in
the metabolism of the neurons which comprise those
nuclei, regional variation of blood flow, and regional
accumulation of lactic acid. - The localizations of
necrotic regions in the brainstem of the present case
includes some of the above mentioned nuclei and tracts
e.g., trigeminal, solitarius, and gracile tracts and nu­
clei. This pathologic observation cannot, however, be
explained solely on the basis of the differential suscep­
tibility of neurons because the necrotic regions extend
well beyond the nuclei to contiguous regions of white
matter.
10
11
Studies of vascular anatomy in the brainstem have
shown that numerous branches leave the vertebrobasi­
lar artery to penetrate the median, paramedian, and
lateral z o n e s . - These arterial zones of supply are
longitudinally oriented along the axis of the brainstem.
Penetrating vessels supplying these areas do not anas­
tomose with others in adjacent areas. When one com­
pares this vascular pattern of brainstem to the localiza­
tion of the lesions in the brainstem of our patient, the
lesions correspond closely to the regions denned by the
convergence of distal fields of distribution of the pene­
trating arteries. - One may speculate that the pro­
longed, severe hypotension in this patient thus resulted
in symmetric infarction in the most distally perfused
regions, in a pattern analogous to the arterial end-zone
pathology found in other subcortical structures. The
hemorrhagic nature of these necrotic areas may be
explained partly on the basis of coagulopathy docu­
mented by laboratory findings in this patient.
The absence of the conventional hypotensive lesions
of cerebral hemispheres in this patient is quite intrigu­
ing and cannot be readily explained. It is conceivable
that the influence of phenytoin and phenobarbital and
17
18
17
18
19
FIGURE 4 .
metric
xl2).
Cross-section
necrosis
surrounded
of medulla
showing
by hemorrhagic
bilateral
zone
sym­
(H & E,
of marked hypothermia protected the cerebral cortex
selectively from the usual anoxic-ischemic changes. A
lower cerebral metabolic rate might also have contrib­
uted to the relatively long survival of the patient, thus
allowing brainstem injury to progress to massive tissue
destruction.
Acknowledgement
We are grateful to Dr. John J. Moran for providing us with the
autopsy material. We thank Mr. Alan Parker for technical help and Mrs.
Peggy Coulter for her secretarial assistance.
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Symmetric brainstem necrosis in an adult following hypotension: an arterial
end-zone infarct?
J C Jurgensen, J Towfighi, R W Brennan and W H Jeffreys
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Stroke. 1983;14:967-970
doi: 10.1161/01.STR.14.6.967
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