Brainstem Stroke: Anatomy, Clinical

and Radiological Findings

Ana Ortiz de Mendivil, MD,* Andrea Alcalá-Galiano, MD,† Marta Ochoa, MD,‡
Elena Salvador, MD,† and José M. Millán, MD†,*

Ischemic brainstem strokes constitute 10% of all ischemic brain strokes. Hemorrhagic
complications are associated with an especially poor prognosis. Associated symptomatology
includes vertigo, cranial nerve symptoms, and crossed or uncrossed corticospinal tract
findings. Advanced neuroimaging techniques have become essential in the decision-making
process of brainstem stroke management and may provide a means to identify those patients
who may benefit from thrombolysis. Because many of the recommendations are based on
limited data, additional research on treatment of acute brainstem stroke is needed.
Semin Ultrasound CT MRI 34:131-141 C 2013 Elsevier Inc. All rights reserved.

S troke is a leading cause of neurologic morbidity and

mortality worldwide. In industrialized countries, stroke
constitutes either the second or the third most common cause
of death along with cardiovascular disease and cancer. In
Europe, the death rate ranges from 63.5/100,000 in Switzer-
land (1992, males) to 273.4/100,000 in Russia (1991,
females).1,2 Stroke is also the second most common cause
of dementia in older age groups, after Alzheimer disease. In
the last decade, important advances in therapy and neuroi-
maging have changed the management of stroke patients.
Favorable clinical results are often obtained using intravenous
thrombolytic agents, especially in patients with posterior
circulation disease.
Acute stroke is defined by a sudden neurologic deficit of
vascular origin lasting more than 24 hours. Stroke can be
classified into 2 major categories: ischemic (80%-85%) and
hemorrhagic (15%-20%).3 Almost one-third of the ischemic
strokes affect the vertebrobasilar system.2 Ischemic brainstem
strokes affect the pons more commonly than the medulla or
midbrain.4
Vascular Anatomy
At the level of the medulla oblongata, 4 territories may be
differentiated (Fig. 1A). The anteromedial group arteries
originate from the anterior spinal artery (ASA) caudally and
*Department of Radiology, University Hospital Madrid Norte Sanchinarro,
Spain.
†Department of Radiology, University Hospital 12 de Octubre, Madrid, Spain.
‡Department of Neurology, University Hospital Madrid Norte Sanchinarro,
Spain.
*Address reprint requests to Ana Ortiz de Mendivil, MD, Department of
Radiology, University Hospital Madrid Norte Sanchinarro, Calle Oña 10,
28050 Madrid, Spain. E-mail: aomendivil@yahoo.es
the vertebral artery (VA) cranially; the anterolateral group
arteries also arise from the ASA and VA; the lateral group
arteries arise from the posterior inferior cerebellar artery; and
the posterior group arteries arise from the posterior spinal artery.
At the level of the pons, we can differentiate 3 intrinsic
arterial territories (Fig. 1B). Anteromedially, supply is from the
pontine perforating arteries arising from the basilar artery
(BA). These penetrate the basilar sulcus. The anterolateral
group arteries arise from the anterior inferior cerebellar artery
entering at the pontomedullary sulcus. The lateral zone is
supplied by the lateral pontine perforators that arise directly
from the BA, from the anterior inferior cerebellar artery, or
from the superior cerebellar artery.
At the level of the midbrain, there are 4 territories (Fig. 1C).
The anteromedial group arteries arise from the posterior
cerebral artery (PCA) at the interpeduncular fossa; the
anterolateral midbrain arteries originate from the PCA or a
branch of the anterior choroidal artery; the lateral group
arteries arise from the collicular, choroidal, and posterior
cerebellar arteries; and the posterior group arteries arise from
the superior cerebellar collicular arteries and posteromedial
choroidal artery.
Most strokes at the level of the pons and medulla are
sharply marginated and paramedian, with the long axis
oriented sagittally. This orientation reflects the distribution
of the paramedian-penetrating branches of the basilar and
distal vertebral arteries, which perforate the paramedian
brainstem and never cross the midline. Lateral infarcts, in
the distribution of the short circumferential arteries, are seen
less frequently than paramedian lesions. At the midbrain
level, midline infarctions can be visualized, as the many
involved branches are not limited to a paramedian
distribution.

0887-2171/$-see front matter & 2013 Elsevier Inc. All rights reserved. 131
http://dx.doi.org/10.1053/j.sult.2013.01.004
132 A. Ortiz de Mendivil et al

Figure 1 (A) Vascular territories at the level of the medulla oblongata. Four well-differentiated territories may be seen:
(1) anteromedial group arteries, (2) anterolateral group arteries, (3) lateral group arteries, and (4) posterior group.
(B) Vascular map at the level of the pons. We can differentiate 3 territories: (1) the anteromedial group, (2) the
anterolateral group, and (3) the lateral group. (C) Vascular territories at the level of the midbrain. As in the medulla,
4 territories may also be seen: (1) anteromedial group arteries, (2) anterolateral group arteries, (3) lateral group arteries,
and (4) posterior group. (Color version of figure is available online.)

Etiology Risk factors associated with brainstem stroke include

Occlusion of the VA and its branches often occurs secondary
to dissection or atherosclerosis and usually causes infarction
in the medulla or inferior cerebellum.
VA dissection is an increasingly described cause of brain-
stem infarct in patients younger than 45 years.5 Several
risk factors are associated with this condition, including
hypertension, fibromuscular dysplasia,6 trauma, and spinal
manipulation.
Bilateral distal vertebral occlusions cause low flow in the
posterior circulation, leading to a stepwise deterioration
reflecting ischemia in the brainstem and the cerebellum.
Thrombotic or embolic occlusion of the BA or its major
branches can lead to ischemia of the pons, the midbrain, and
the cerebellum.7
Occlusion of a small penetrating artery from the BA
can lead to a lacunar syndrome. Multiple areas of
infarction can occur simultaneously in the posterior
circulation.7
hypertension, diabetes mellitus, cardiac disease, hyperlipide-
mia, smoking, a positive family history of brainstem stroke,
obesity, and use of oral contraceptives.
Medullary Infarction (MI)
MIs account for 7% of all ischemic brainstem strokes. Lateral
MIs (LMIs) are 3-4 times more common than medial MIs
(MMIs); there is a 3:1 male predominance.8
Atherosclerosis of the VA and its branches is the most
common cause of MI.9 VA dissection is another important
cause (20%-30%) of both LMI and MMI8 and should be
suspected in the context of neck pain and medullary
symptoms, particularly in young patients.
MMI (Dejerine Syndrome)
The classic triad of contralateral hemiparesis, contralateral
loss of position and vibration sense, and ipsilateral tongue

Figure 2 Dejerine syndrome. A 58-year-old patient with a sudden onset of vertigo, left hemiparesis, left hemihypoesthesia,
and ataxia. (A) Axial SE T2-weighted reveals a sagittal band shape of slightly high intensity involving the right medial
medullary region. (B) Diffusion-weighted imaging shows a high intensity on isotropic image consistent with acute
ischemic infarction. Note the precise borders and the correspondence with the anteromedial vascular territory. SE, spin-
echo.
Brainstem stroke: anatomy, clinical and radiological findings 133

Table 1 Brainstem Stroke Syndromes

Structures Deficit
Medullary stroke
Medial Dejerine’s anterior
Corticobulbar tract Dysarthria
Corticobulbar tract CL hemiparesis
Medial lemniscus CL loss position sense and vibration
Medial longitudinal fasciculus IP internuclear opthalmoplegia
CN 12 nucleus IP weakness half of tonque
Lateral Wallenberg
Spinal trigeminal nucleus/tract IP absent corneal reflex, facial numbness
Lateral spinothalamic tract CL arm/trunk/leg numbness
Inferior cerebellar peduncle IP ataxia
Vestibular nuclei Vertigo, nausea and vomiting
Sympathetic fibers IP Horner syndrome
Nucleus ambiguus Dysphagia,dysarthria, hoarse vioce

Anteromedial pontine stroke

Corticobulbar tract Dysarthria, CL facial palsy
Corticospinal tract CL hemiparesis
Corticopontine tract CL ataxia, pathologic laugther
Medial lemniscus CL loss position sense and vibration
Medial longitudinal fasciculus IP internuclear ophthalmoplegia
CN 6 nucleus, 7 fibers IP lateral rectus palsy, IP facial weakness
Paramedian pontine reticular formation IP horizontal gaze paresis

Anterolateral pontine stroke

Corticospinal tract CL hemiparesis, CL ataxia
Spinothalamic tract CL loss body pain, temperature sensation (more severe in lower extremities)

Bilateral pontine stroke (locked in syndrome)

Corticospinal tract Quadriplejia
Corticobulbar tract Aphonia/dysphagia
Paramedian pontine reticular formation Bilateral horizontal gaze paresis
CN 7 fibers/nucleus Bilateral facial weakness
Reticular formation Transient lethargy

Dorsolateral pontine stroke

Caudal pons
Lateral corticospinal tract CL hemiparesis leg4arm
Spinal nucleus/tract of 5 IP loss facial pain, temperature sensation
CN 7 fibers/nucleus IP facial weakness
CN 8 hearing loss
Cerebellum Ataxia
Rostral pons
Sympathetic tract IP Horner syndrome
Spinothalamic tract CL or trunkal ataxia
Superior cerebellar peduncle CL loss body pain, temperature sensation

Anterior midbrain stroke

Medial
Corticospinal tract CL hemiparesis, CL ataxia
Corticobulbar tract Dysarthria
Red nucleus CL choreoathetosis, coarse tremor
Superior cerebellar peduncle CL ataxia
CN 3 fascicle IP CN 3 palsy
Lateral
Corticospinal tract CL hemiparesis
Medial spinothalamic tract CL loss of pain and temperature sensation
Superior cerebllar peduncle CL ataxia
134
Table 1 (continued )
Structures
Dorsolateral midbrain stroke
Dorso
Superior/inferior colliculi Vertical gaze palsies
Posterior comisure Loss of accomodation, pupillary light reflex
CN 3 nucleus IP CN 3 palsy, bilateral ptosis, CL paresis upward gaze
CN 4 nucleus CL superior oblique weakness
Lateral
Descending sympathetic fibers IP Horner syndrome
Lateral spinothalamic tract CL loss body pain, temperature sensation
CN, cranial nerve; CL, contralateral; IP, ipsilateral.
weakness is not always present (Fig. 2, Table 1). Oculomotor
abnormalities and dysarthria may be present.
LMI (Wallenberg Syndrome)
Patients may present with ipsilateral vocal and palatal
paralysis, ipsilateral facial sensory loss, ipsilateral Horner
syndrome (ptosis, miosis, and anhydrosis), ipsilateral ataxia,
and loss of pain and temperature sense, with a crossed pattern
affecting the contralateral body and ipsilateral face (Fig. 3). In
addition, there may be nystagmus, vertigo, nausea, and
diplopia.
Hemimedullary Infarction (Babinski-Nageotte
Syndrome)
Occlusion of the ipsilateral VA proximal to the posterior
inferior cerebellar artery and its ASA branches causes LMI and
MMI simultaneously.
Pontine Infarction
Isolated pontine strokes are relatively frequent, but they can
occur as part of a larger infarction in the posterior circulation
(Table 1).10 Atherosclerotic disease of perforating arteries and
occlusion or stenosis of the BA are the most common causes
of pontine infarct.
Ventral infarcts are the most common type of isolated
pontine infarction (51%-58%) and result from occlusion of the
anteromedial and the anterolateral arterial groups.10,11
Anteromedial infarct (Fig. 4) causes hemiparesis or hemi-
plegia, contralateral ataxia, dysarthria, dysphagia, nystagmus,
and often ipsilateral facial palsy. Less frequently associated is
contralateral loss of proprioception, paresis of the ipsilateral
horizontal gaze, and internuclear ophthalmoplegia.
Lacunar disease is a common cause of pontine stroke. Four
varieties are described: pure motor, dysarthria-clumsy hand,
ataxic hemiparesis syndrome, and pure sensory stroke.
Several classic syndromes have been reported in association
with pontine stroke. These include Millard-Gubler syndrome
(lateral rectus palsy, ipsilateral facial weakness, and contral-
ateral hemiparesis), Landry syndrome (ipsilateral abducens
A. Ortiz de Mendivil et al
Deficit
palsy and contralateral hemiparesis), and Raymond-Cestan
syndrome (ipsilateral conjugate gaze palsy and contralateral
sensory and motor deficits).
Anterolateral infarct may produce hemiparesis, ataxia, loss
of position sense, and loss of vibration sense. Pure motor
stroke, ataxic hemiparesis, dysarthria-clumsy hand, or sen-
sorimotor stroke are the other forms of manifestation of the
anterolateral strokes. When sensory abnormalities involve
lower extremities, an anterolateral stroke may be suspected.
Dorsolateral pontine strokes may lead to contralateral
hemiparesis, ipsilateral facial weakness, ipsilateral loss of
facial pain and temperature sensation, hearing loss, and
ataxia. Rostral dorsolateral pontine infarct can manifest as
ipsilateral Horner syndrome, contralateral ataxia, and con-
tralateral loss of body pain and temperature sensation.
Isolated dorsal infarcts (medial tegmental or lateral teg-
mental) are very rare, and normally they occur as a part of
larger infarction in the posterior circulation.
Two main syndromes arise from infarcts in dorsal distribu-
tion: Foville syndrome (ipsilateral conjugate gaze palsy and
contralateral hemiparesis) and Foix-Chavany-Marie syn-
drome (ipsilateral ataxia, contralateral sensory loss to pinprick
sensation, and temperature and contralateral hemiparesis).
Midbrain Infarction
The arterial blood supply to the midbrain is complex. Infarcts
limited to the midbrain are uncommon and usually are
accompanied by involvement of other structures such as the
cerebellum, thalamus, and pons.12
Small dorsal strokes are usually caused by occlusion of
penetrating branches from the BA, whereas proximal PCA
atherosclerosis is the usual pathogenic mechanism in lesions
involving the anterior midbrain. Medial surface involvement
is usually related to the P1 segment of the PCA, and lateral
involvement is associated with the P2 segment. Embolism is
an uncommon cause of midbrain stroke.12 Dissections are
also an uncommon pathogenic mechanism.13 Hypertension
is the most frequent risk factor for midbrain strokes. Other
risk factors include diabetes, smoking, atrial fibrillation,
hyperlipidemia, and atherosclerotic ischemic heart disease.
Brainstem stroke: anatomy, clinical and radiological findings 135

Figure 3 Wallenberg syndrome. A 46-year-old woman complaining of classical lateral medullary symptoms: crossed
sensory pattern affecting the ipsilateral face and contralateral body, Horner syndrome, vertigo, diplopia, ataxia, nausea,
and dysphagia. (A) Axial T2-weighted image shows an infarct in the right lateral medullary segment (black arrow).
(B) Diffusion-weighted MR imaging confirms the acute infarct (white arrow). (C) Note the low value of the signal on the
ADC map (black arrow). (D) MR angiography revealed a right vertebral artery dissection (thin arrows).

Figure 4 Anteromedial pons infarct. A 62-year-old patient with left hemiparesis, ataxia, dysarthria, dysphagia, nystagmus,
and paresis of ipsilateral horizontal gaze. (A) Axial T2-weighted magnetic resonance imaging shows a slight
hyperintensity in the right medial pons. (B) Diffusion-weighted MR imaging confirms the presence of an acute
anteromedial pontine stroke. (C) Note the low signal on the ADC map.
136
Figure 5 Dorsal midbrain infarct. A 62-year-old patient with vertigo, diplopia, and vertical gaze palsy. (A) Axial T2-
weighted image did not show any abnormality. (B) Axial isotropic diffusion-weighted MR images. (C) ADC map shows
the typical imaging features of acute ischemic infarct in the left dorsal vascular territory.
Clinical features of midbrain infarcts include third nerve
palsy, supranuclear conjugate vertical gaze palsies, disconju-
gate vertical gaze palsies, skew deviations, and convergence-
retractory nystagmus.
Anteromedial midbrain strokes may manifest as ataxia,
contralateral hemiparesis, contralateral choreoathetosis, and
ipsilateral third cranial nerve palsy. Several syndromes have
been described: Weber syndrome (ipsilateral third nerve palsy
with contralateral hemiparesis), Benedict syndrome (ipsilat-
eral third nerve palsy with contralateral choreoathetosis or
coarse tremor), and Claude syndrome (ipsilateral third nerve
palsy and contralateral ataxia).
Anterolateral midbrain strokes theoretically cause contral-
ateral hemiparesis, contralateral ataxia, loss of contralateral
vibration and position sense, and loss of pain and temperature
sense in the trunk and extremities.
Lateral infarcts may lead to contralateral hemiparesis (lower
extremities), loss of pain and temperature sensation in the
contralateral trunk and extremities, contralateral or ipsilateral
hearing loss, and Horner syndrome.
Dorsal midbrain infarct (Fig. 5) causes diplopia, vertical
gaze abnormalities, and other oculomotor syndromes. In
addition, it may induce tinnitus, hyperacusis, and loss of
auditory acuity.
The top of the basilar syndrome is usually embolic in
nature and is usually associated with damage to the thalamus
and the temporal and occipital lobes. Abnormalities in
consciousness, memory disturbances, akinetic mutism, ipsi-
lateral oculomotor syndromes, contralateral hemiparesis,
contralateral sensory loss, ipsilateral or contralateral limb
ataxia, and flapping tremor may be present.
Imaging Workup
Computed tomography (CT) results are commonly negative
early in the course of ischemic brainstem stroke.14,15 The
hyperdense BA and subtle signs of hemorrhage must be
carefully sought.16
CT angiography (CTA) is a precise technique for assessing
the level of intracranial vascular occlusion in patients pre-
senting within 6 hours of stroke onset (Fig. 6). CTA also
A. Ortiz de Mendivil et al
provides useful information for patients in therapeutic trials.
CTA source images can also be used to delineate infarct size.17
First-pass CT perfusion (CTP) can detect functional
abnormalities by measuring tissue-level blood flow. This flow
can be assessed using a variety of parameters: cerebral blood
flow, cerebral blood volume (CBV), and mean transit time.
The region of CBV abnormality represents the location and
extent of the ischemic brain area (‘‘the core’’). Viable hypo-
perfused tissue, the volume of tissue contained within the
region of cerebral blood flow–CBV mismatch that surrounds
the irreversibly infarcted tissue, is referred to as the penumbra.
Magnetic resonance imaging (MRI), in particular diffusion-
weighted (DW) MRI combined with perfusion imaging, is in
general superior to CT in discriminating areas of reversible
ischemia from irreversibly infarcted tissue or ‘‘core’’ infarct.18-
20
DW MRI is extraordinarily sensitive to the net translational
movement of water molecules. When placed in a strong
magnetic field gradient, the translational movement of water
protons produces a phase shift that can be detected as relative
signal loss compared with regions of reduced water motion.
DW MRI is usually acquired in 3 directions and with different
b values (diffusion-sensitizing gradient pulse) to generate
isotropic images. Apparent diffusion coefficient (ADC) maps
are calculated. Usually DW MRI is acquired with b ¼ 1000 s/
mm2,21 but b ¼ 1100 s/mm2 values are also utilized.21 The
usefulness of the absolute ADC calculation in cases of
brainstem infarct is still unknown. Preliminary studies using
DW MRI have proved that an early infarct is depicted as
regional high-signal intensity when compared with that of the
background tissue.22 The ADC map is used to leave out ‘‘T2
shine through’’ as the cause of the high signal on DW MRI.
Diffusion-weighted imaging (DWI) has been used to illustrate
acute cerebral infarctions, with a sensitivity of 88%, a
specificity of 95%, and a false-positive rate of 1.5%.18 DW
MRI is readily performed in patients who cannot tolerate
conventional MRI, as the echo planar implementation image
acquisition occurs in subsecond time frames.22
In the first 24 hours, the rate of false-negative DW MRI
studies is much higher in posterior circulation strokes (31%)
than in those involving the anterior circulation (2%). Oppen-
heim et al.23 reported false-negative DWI results in 34% of
patients with brainstem stroke during the first 24 hours. The
Brainstem stroke: anatomy, clinical and radiological findings
inability to detect acute lesions might be attributable to limited
resolution and issues related to magnetic susceptibility.18,24,25
Prompt follow-up imaging in patients with normal results on
initial DWI and persistent neurologic deficit is recommended.
Sensitivity in the detection of small lesions may be increased
by utilizing higher resolution with thinner sections and by
combining axial and coronal DWI sequences.26
The demonstration of restricted diffusion is considered
indicative of irreversible tissue damage in the majority of
cases. DWI reversibility has been described in venous
infarction, hemiplegic migraine, transient global amnesia,
and status epilepticus.27 In the setting of intravenous or
intra-arterial thrombolysis or both, DWI reversibility is more
common: 12%-33% of initial DWI.28 Magnetic resonance
angiography may be useful if DWI results are negative.29
The usefulness of perfusion MRI, or perfusion-weighted
imaging (PWI), in the evaluation of stroke has been reported
by different groups.19,30 They were able to demonstrate
cerebral infarction and ischemia soon after onset of symp-
toms. Areas of ischemic penumbra may also be detected by
using relative subtraction of diffusion abnormalities from
perfusion deficits.31 Ostrem et al.32 revealed that the
diffusion-perfusion mismatch can be observed clearly in the
posterior circulation, including the brainstem, 6 hours after
symptom onset. Improvement of this penumbra region after
recanalization of the BA with intra-arterial thrombolytic
therapy was also demonstrated. There is a difference in
opinion, however, regarding this technology. Other authors
were unable to identify DWI or PWI mismatches consistently
and to determine which patients were candidates for
thrombolysis.33
As CTP has substantial spatial resolution and a linear
relationship between attenuation and contrast concentration,
CT may be employed for quantification. Indications are that
visual assessment of the core or penumbra mismatch is more
dependable with CTP than with MR PWI.28,30 However, a
major drawback of current CTP techniques is the relatively
limited coverage. MR PWI is capable of acquiring information
regarding the whole brain, whereas CTP cannot.
We can conclude that both CT and MRI provide informa-
tion on the state of brain parenchyma, the vessels, and brain
tissue perfusion. CT is superior in detecting hemorrhage. CTA
is highly accurate for the detection and exclusion of large
vessel occlusion. Diffusion MRI may be more accurate for
detecting irreversibly infarcted brain parenchyma, and
because of its complete coverage of the whole brain, MR
PWI seems to be more useful for evaluating viable parench-
yma in danger of infarction.28
Prognosis
Posterior circulation stroke has traditionally been considered
an entity with high morbidity and mortality, although recent
authors have experienced substantially lower mortality rates
than others.29,34 Patients with dysarthria, pupillary disorders,
lower cranial nerve involvement, and disorders of
137
consciousness on admission had the worst prognostic values
compared with those with other clinical syndromes.35
Differential Diagnosis
All acute ischemic events should demonstrate diffusion
restriction signal with low values on the ADC map, whereas
subacute to chronic lesions should demonstrate no restriction
signal with high values on ADC maps.
Neoplastic disease, in particular pontine glioma, may have
similar MRI features but much more commonly will have
mass effect, and an acute clinical presentation is much less
likely. Spectroscopy MRI may lead to an accurate diagnosis.
Central pontine (osmotic) myelinolysis usually occurs in
severely ill patients. MRI will classically demonstrate a trident-
shaped, central pontine signal intensity. In the acute phase,
DWI reveals restricted diffusion and corresponding low ADC
values.36
Acute disseminated encephalomyelitis and multiple sclero-
sis may result in similar signal intensity changes masquerad-
ing as acute ischemic events, but enhancement characteristics
and clinical time course ordinarily differ (Fig. 7).
Diffuse axonal injury (DAI) involving the midbrain after
head trauma may also appear similar to ischemic disease on
MRI; however, periventricular white matter and splenial
involvement, in additional to the patient history, should
suggest DAI. Moreover, gradient-echo sequences should
allow demonstration of the paramagnetic effect of character-
istic petechial hemorrhages.
False-positive DWI images have been reported with
cerebral abscess (restricted diffusion due to increased viscos-
ity), venous infarction, and hemorrhage.18
Management
Intravenous administration of recombinant tissue plasmino-
gen activator is the only medical therapy approved for the
management of patients with acute ischemic stroke by the US
Food and Drug Administration. It is recommended for
selected patients within 3 hours of the onset of ischemic
stroke.37-39
Intra-arterial administration of thrombolytic agents appears
to be beneficial in the treatment of rigorously selected patients
who have experienced acute ischemic stroke that is related to
occlusion of the middle cerebral artery. To this date, there are
no randomized, placebo-controlled studies in the literature of
intra-arterial thrombolysis for vertebrobasilar occlusion, so
the time window for a posterior circulation stroke has not
been well established. Successful thrombolysis with improve-
ment of the clinical outcome has been reported after 24 hours
(Fig. 6).37,40 Nevertheless, it is also possible that some
patients, even when treated within the first 6 hours from
onset, will not benefit from therapy. Multimodal MRI may
provide a means to identify those patients who may benefit
from both early and late therapy. Recent evidence indicates the
usefulness of intra-arterial urokinase in patients with vertebral
or BA occlusion treated within 24 hours.38
138 A. Ortiz de Mendivil et al

Figure 6 Locked-in-syndrome. A 53-year-old man, with abrupt onset of slurred speech, right hemiparesis, and
drowsiness. (A) Axial unenhanced-computed tomography reveals hyperdense basilar artery tip (arrow). (B-D) MIP
reconstruction and volume rendering CT angiography reveal the presence of a clot in the basilar artery. (E, F)
Angiography confirms basilar artery occlusion. (G) Partial recanalization (white arrows) was achieved after superselective
infusion of r-TPA. Note the presence of a residual clot in the right posterior cerebral artery. MIP, maximum intensity
projection; r-TPA, recombinant tissue plasminogen activator. (Color version of figure is available online.)

Brainstem Hemorrhagic Events
Approximately 6%-10% of all brainstem hemorrhages are due
to ischemic events.41-44 Pontine involvement is most com-
mon, medullary involvement the least common. The great
majority of cases manifest acutely; subacute or chronic
symptomatology is very rare.44,41 The classic clinical setting
of coma, tetraparesis, respiratory failure, and oculomotor
signs is still the most frequent form of presentation, and most
patients have diminished sensorium.41,42,44 Some authors
describe prodromal symptoms, such as headache, nausea,
and vomiting, respiratory dysfunction, and dysarthria.41
Brainstem hemorrhages can be either spontaneous (hyper-
tensive, cavernous angioma) or posttraumatic.
Hypertension is the most common cause of brainstem
hemorrhage, accounting for about 90% of cases.42,44 Most
occur in the dorsal pons mainly because of the characteristic
vascular supply via direct perforating arteries.47 Patients on
anticoagulant therapy (7%) usually present with larger hema-
tomas and have a poorer prognosis.42,44
CT will, of course, demonstrate high attenuation within
the brainstem (Fig. 8). Hypertensive hemorrhages typically
do not enhance, although some hematomas may show mild
enhancement of the wall, which complicates the diagnosis.43
MRI allows accurate depiction of the location and extension
of the hemorrhage.
Chung and Park45 classified pontine hemorrhage into
3 groups: dorsal, ventral, and massive. Dorsal location included
small, unilateral, tegmental, and bilateral tegmental hemor-
rhages sparing the basis pontis. The ventral group consisted of
hemorrhages in the ventral basis pontis (basal tegmental).
Massive hemorrhages were those occupying the basis pontis
and bilateral tegmentum and extending into the midbrain.46,47
Kase and Caplan48 classified pontine hemorrhages into 3 sub-
types: large paramedian hemorrhage, unilateral basal or baso-
tegmental hemorrhage, and lateral tegmental hemorrhage.
The dimensions of the hematoma may be evaluated by
2 parameters: the volume and the maximum transverse
diameter.41,44,49,50 The ‘‘bedside’’ formula for calculating the
volume of a hematoma, proposed by Kothari et al. in 1996,49
is as follows: hemorrhage volume (mL) ¼ (A  B  C)/2, A
being the largest diameter of the hemorrhage, B the diameter
perpendicular to A, and C the number of CT sections  the
section thickness. Today, with multidetector computed
Brainstem stroke: anatomy, clinical and radiological findings 139

Figure 7 Multiple sclerosis mimicking acute infarct in a 36-year-old woman. (A, B) Axial T2- and sagittal FLAIR-weighted
images demonstrate high-signal hyperintensity in the left anteromedial medulla (arrow) consistent with a demyelinating
lesion. FLAIR, fluid-attenuated inversion recovery.

tomography, this formula is easier to calculate by simply using
the 3 spatial diameters of the hemorrhage: transverse, ante-
roposterior, and craniocaudal.
Brainstem hemorrhages caused by rupture of arteriove-
nous malformations typically occur in younger patients.
These hemorrhages tend to be subependymal, are generally
smaller, and have a better prognosis than that of hyperten-
sive hematomas. True arteriovenous malformations rarely
occur in the posterior fossa. Most are ‘‘angiographically
occult’’: cavernous hemangiomas and capillary telangiecta-
sia.47,51-53 The diagnosis of these occult vascular malforma-
tions is greatly facilitated by MRI. Both capillary
telangiectasia and cavernous hemangioma may be located
anywhere in the central nervous system; cavernous angio-
mas have a predilection for the supratentorial region,
whereas capillary telangiectasia is found mainly in the
pons.53,54 Capillary telangiectasia, however, rarely manifests
with macroscopic hemorrhage, unlike cavernous malforma-
tions in the brainstem, which have a higher bleeding rate.
Both lesions may coexist and can represent 2 ends of a
spectrum of angiographically occult vascular malformations.
Cavernous angiomas (also known as cavernous hemangio-
mas, cavernous malformations, or cavernomas) account for
5%-13% of all vascular malformations in the central nervous
system51,52,55,56 and have a prevalence of 0.4%-0.9%.56
Cavernous angiomas may be solitary or multiple, sporadic
or familial. They are much more frequent in the supratentorial
region (80%) and have a propensity for the frontal and
temporal lobes. Brainstem cavernomas account for 9%-35%
of all cavernous malformations and appear most frequently in
the pons (60%). The remainder are equally distributed
between the midbrain and the medulla (20%).51,52,55,56 About
20% of these lesions are asymptomatic52; others manifest
with headache, seizures, and neurologic deficits mostly
related to hemorrhagic phenomena. Brainstem cavernomas
have a high incidence of hemorrhage and rebleeding and
carry high neurologic morbidity.51,52,56,57 The bleeding
rate is about 2.7%-5% per year, and the average rebleeding
rate reaches up to 21%-34.7% per year per lesion.55,56 In
multiple cavernomatosis (familial in 85% and sporadic in
15%),51 the risk of hemorrhage is 2.5% per year and per
lesion.58

Figure 8 Pontine hemorrhage in a 68-year-old man. (A) Axial unenhanced-computed tomography shows a pontine
hemorrhage extending to left anterior midbrain (arrow).
140
Cavernous angiomas generally appear as nodular high-
density areas on noncontrast CTscans, occasionally enhancing
with contrast. Diagnosis with MRI is easier owing to char-
acteristic hemosiderin deposition on T2-weighted (T2W) and
gradient-echo images. A lesion with a central area of mixed
signal intensity, commonly known as ‘‘popcorn’’ appearance,
and a surrounding rim of decreased signal intensity (hemosi-
derin rim) on T2W image (T2WI) is the classic finding.52,53
On digital substraction angiography, no feeding arteries are
seen, although a subtle blush or early draining vein may be
observed.51,52 Surgical intervention is controversial.52,55-57
Capillary telangiectasias are not uncommon. At autopsy,
their estimated prevalence is 0.4%,59 and they account for
16%-20% of all intracerebral vascular malformations.53,59
They are most common in the pons and are usual-
ly o2 cm.53,54,59 Symptoms include headache, vertigo, or
subtle neurologic deficit. Most capillary telangiectasias are
asymptomatic.53,59 These lesions usually lack mass effect or
calcification, and macroscopic hemorrhage is rare, making
these lesions undetectable on unenhanced CT.53,59 Capillary
telangiectasias are being increasingly recognized on MRI.53
They are poorly seen on T1WI but may show focal areas of
slightly increased signal intensity on T2WI. Because they lack
hemosiderin, they are not hypointense on T2WI, which
distinguishes them from cavernous angiomas. Capillary
telangiectasias usually exhibit susceptibility dephasing man-
ifest by hypointensity on T2*-weighted gradient-echo images
owing to the presence of deoxyhemoglobin.54,59 They
enhance only mildly with gadolinium.53,54,59 As such,
gradient-echo is essential in the diagnosis.
Hemorrhagic necrosis of the pons associated with osmotic
vascular injury is rare.60 Amyloid angiopathy is also a rare
cause of brainstem hemorrhage, accounting only for about 3%
of the cases.44
Trauma
Brainstem involvement in patients with head trauma is
relatively common. Direct traumatic lesions usually affect
the rostral ventral portion of the mesencephalon adjacent to
the interpeduncular cistern.61 Brainstem involvement in DAI
is associated with a more severe injury.51 Eighty percent of
DAI lesions are nonhemorrhagic,51 but petechial lesions
typically can be seen in the posterior lateral quadrants of
the brainstem.47,51 CT is very useful in the early evaluation of
brainstem injury, but the mainstay in the diagnosis is MRI,
which can depict the true extent of involvement
accurately.51,61
Duret hemorrhages occur in the ventral portion of the
midline of the lower mesencephalon and upper pons as a
result of a transtentorial herniation and are rarely encountered
on imaging.47 The incidence reported in radiologic studies
(5%-10%) is significantly lower than that reported in autopsy
series (30%-60%), in part because up to 20% of these
hemorrhages are microscopic and because patients typically
do not survive long enough for follow-up imaging.
The prognosis for brainstem hemorrhage is clearly worse
than that for brainstem ischemic stroke, with an overall
A. Ortiz de Mendivil et al
mortality rate of 30%-88%.41,42,44 The size and location of the
hemorrhage are closely related to the outcome.62 Massive
hemorrhages and ventral or paramedian hemorrhages indi-
cate a poor prognosis (7.1% survival).41,45 The unilateral
tegmental subtype is associated with a more favorable out-
come.41,45 Basotegmental hemorrhages have an intermediate
prognosis.41
Conclusions
Recently developed neuroimaging techniques, including CTP
and MRI with DWI or PWI, have become indispensable in the
decision-making process of brainstem stroke management
and may provide a means to identify patients who may benefit
from intravenous or intra-arterial thrombolysis.
The most common cause of brainstem hemorrhage is
hypertension. Cavernous angioma is the most frequent
vascular malformation in the brainstem and has a strong
tendency to bleed. The prognosis is poor and depends on the
clinical symptoms as well as on the location and extension of
the hemorrhage. Treatment is usually conservative.
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