Journal of Neurology, Neurosurgery, and Psychiatry 1983 ;46:221-226

Premonitory symptoms of stroke in evolution to the
locked-in state
JOHN LIU, STANLEY TUHRIM,* JESSE WEINBERGER,* SUN K. SONG,t PAUL J
ANDERSONt
From the Department of Neurology* and Division of Neuropathologyt The Mount Sinai School of Medicine,
City University of New York, and the Division of Neuropathology, City Hospital Centre at Elmhurstt, New
York, USA
SUMMARY Three patients, who subsequently developed the locked-in state characterised by
quadriplegia and mutism with an alert sensorium, initially had mild dysarthria and uncrossed
hemisensory or hemimotor deficits involving the face and ipsilateral extremities. Case one initially mimicked a left cerebral lesion with right hemisensory deficits, a mild right facial paresis and
a right homonymous field deficit. Case two initially developed both left hemimotor and hemisensory deficits and later developed a paresis of right conjugate gaze. Case three presented with left
hemimotor deficit, and mild paresis of conjugate gaze to the right. All three patients died. Rostral
brainstem infarctions were found at necropsy in cases one and two. Case three had a radiolucent
area of the brainstem demonstrated by CT Scan. Hemisensory and hemimotor deficits also have
been noted to precede reported cases of pontine infarction with the locked-in state. Acute onset
of uncrossed hemisensory and hemimotor deficits with dysarthria may be caused by infarction of
the pons which may predispose to the locked-in state.

The locked-in state is a devastating neurological
syndrome secondary to infarction or hemorrhage
in the ventral and rostral pons (-15). Patients are
unable to move their extremities or speak, but are
alert and responsive. They communicate with
vertical eye movements and lid movements.
Horizontal eye movements usually are impaired.
The locked-in state can occur acutely, but often
premonitory symptoms are present.
We report three cases of patients who presented
with mild neurological deficits preceding the
development of the locked-in state. All three initially had dysarthria and a mild uncrossed hemisensory or hemimotor deficit involving face and
extremities on the same side. They were all felt to
have had a mild cerebral or brainstem vascular accident, until the locked-in state evolved. Post-mortem
examination was obtained in two patients. In one, a
large infarction of the rostral pons at the mesencephalic junction was identified. In the second, a smal-

ler infarction in the midventral pons was found.
Both had infarctions involving the pyramidal tract
above the facial nucleus. This accounted for the initial symptomatology involving the face and limbs on
the same side. In the third case, a brainstem lesion
was revealed by computed tomography (CT).
These cases illustrate that patients presenting with
symptoms of dysarthria and uncrossed hemisensory
or hemimotor deficits may have ischaemic lesions in
the ventral or rostral pons which may progress to the
locked-in state.

Case reports

Case 1 A 75-year-old diabetic, hypertensive woman
was admitted with slurred speech, dizziness and
unsteadiness of gait of one day's duration. She had
noted circumoral numbness a few days earlier. She
denied diplopia, vomiting, prior weakness or sensory loss. Medications were tolbutamide and
methyldopa. The blood pressure was 200/100
Address for reprint requests: Dr Jesse Weinberger, The Mount
mmHg and pulse was 69/minute. She was alert,
Sinai School of Medicine, 1 Gustave Levy Place, New York, New
oriented
and named objects well. Speech was dysarYork 10029, USA
thric. There was a right homonymous hemianopia
but objects could be located in the affected field.
Received 3 July 1982 and in revised form 29 October 1982
Accepted 13 November 1982
Pupils were equal and reactive. Fundi were normal.
221

222
Ocular movements were normal. There was a mild
right facial paresis with drooling from the right
corner of the mouth. The right palpebral fissure was
wider than the left. Right facial sensation was
diminished to light touch. Strength was unimpaired
bilaterally and reflexes were symmetrically active
with flexor plantar responses. Vibration and light
touch sensation were impaired on the right side.
Pin-prick and position perception were normal.
Rapid alternating movements were slightly impaired
bilaterally, more on the right. The heel to knee to
shin manoeuvre was clumsy on the right. She walked
with an unsteady shuffling gait. Spinal fluid, blood
chemistries, haematocrit and sedimentation rate
were normal.
Twelve hours later, she was found to be unresponsive with Cheyne-Stokes respirations. Blood pressure was 200/90 mmHg and pulse was 60/min. Eyes
were deviated downward without response to
oculocephalic manoeuvre or to cold water caloric
testing. Pupils were 1-5 mm bilaterally and minimally reactive to light. Corneal responses were
depressed bilaterally. There was a quadraparesis
with slight extensor posturing of the upper
extremities to noxious stimuli. Reflexes were 3+
bilaterally with bilateral extensor plantar responses.
She was placed on a respirator. Computed tomography revealed a left sided pontine lucency. Two days
later, the patient had upper facial grimacing with
crying when spoken to by her sister. Pupils were at 2
mm and reactive to light. Resting gaze was disconjugate with slight right eye adduction. The patient
looked down and upward to the midline from a
down position upon command. Gaze above the midline was impaired. She had no horizontal eye movements on passive head turning or ice water caloric
testing. Opticokinetic response to a striped drum
was absent in all directions. Corneal reflexes were
present bilaterally. She could not raise her eyebrows
or forcefully close her eyelids to command. She was
quadraparetic with extensor posturing of the arms
and slight withdrawal of the lower extremities to
painful stimuli. She developed a fever and died three
weeks later.
Necropsy disclosed severe atherosclerosis involving aortic, renal iliac, coronary and carotid arteries.
There was bilateral bronchopneumonia of recent
origin. Examination of the brain disclosed severe
atherosclerotic plaque formation within the vertebral and basilar arteries. Multiple cross-sections
through these vessels disclosed varying degrees of
narrowing of the lumen, most pronounced in the
mid-portion of the basilar artery overlying the base
of the pons. Dissection of the cerebrum disclosed a
well circumscribed old infarct in the head and body
of the right caudate nucleus, measuring 0*5 cm in

Liu, Tuhrim, Weinberger, Song, Anderson
maximal diameter. There were bilateral, wedgeshaped recent infarcts of the medial and ventral surfaces of the occipital lobes, each measuring 3 to 4 cm
in maximal extent. Examination of the brain stem
disclosed extensive recent infarction of the crus
cerebri and tegmentum and base of pons bilaterally
(fig 1). Within the pons, the zone of infarction
measured 2*5 cm rostrocaudally, 2-0 cm transversely, and 1-5 cm dorsoventrally.
Microscopic examination disclosed multiple
recent infarcts in the calcarine cortex of both occipital lobes. Focal infarcts were also present in the
thalamus. The most extensive zone of infarction
involved most of the base of the rostral and midportions of the pons. At the level of the middle
cerebellar peduncle, the infarction extended dorsally to destroy most of the pontine tegmentum.
Rostrally, the infarct extended into both crus cerebri
where extensive portions of the substantia nigra and
fiber tracts of the crus were destroyed. Recent focal
infarcts were also present in the central white matter
of the cerebellum. The medulla contained irregular
zones of rarefaction and there was descending
degeneration in both corticospinal tracts. Swollen
axonal fragments and reactive hyperplastic astrocytes were observed in the medullary pyramids
and the lateral funiculi of the cervical spinal cord.
Sections of the basilar artery showed severe
atherosclerotic narrowing of the lumen, but no areas
of occlusion were found. All of the above described
infarcts were of similar recent age, while the focal
infarct in the right caudate nucleus was considerably
older.
The neuropathological diagnoses were: (1)
infarct, recent, extensive, of pons, mid-brain, cerebellum, thalamus, and occipital lobes bilaterally, (2)
descending degeneration, recent, of corticospinal
tracts, (3) infarct, old, focal, right caudate nucleus,
(4) atherosclerosis, severe, basilar artery.
Case 2 A 67-year-old white male complained of
three days of pain in his left ear and episodic
unsteadiness of increasing frequency lasting approximately fifteen minutes. He also complained of
episodes of numbness and tingling of the left arm
and face associated with slurred speech. Initial
neurologic examination was unremarkable. Upon
awakening seven days after onset of symptoms, the
patient was noted to have slurred speech, a right
conjugate gaze paresis, left central facial nerve palsy
and a mild left hemiparesis. The patient reported
decreased sensation to pinprick over the entire left
side of the body, including the face. Position sense
was preserved. Over the next twenty-four hours the
patient became quadriplegic with bilateral extensor
posturing and bilateral extensor plantar responses,

Premonitory symptoms of stroke in evolution to the locked-in state

223

Fig 1 Case 1. Transverse sections through mid and caudal levels ofmidbrain (upper left and centre) and
rostral level ofpons (lower right). Extensive recent infarct destroys most of the tegmentum and base of the
pons and extends rostrally to destroy portions ofthe crus cerebri.
but he remained responsive to verbal stimuli.
Examination of the cerebrospinal fluid was within
normal limits. A CT scan without contrast performed a week later revealed no abnormality. Subsequently the patient regained some motion of the
right upper and lower extremities and was able to
follow commands with his eyes but could not speak.
He developed pneumonia and died two weeks after
the initial event.

Necropsy disclosed generalised atherosclerosis
with an old healed myocardial infarct on the left
lateral wall. There was bilateral bronchopneumonia
with pleural effusion and pulmonary emphysema.
The brain showed moderate to severe atherosclerotic plaque formation within the veretebral and basilar arteries. Cross sections through these vessels
revealed varying degrees of narrowing of the lumenl,
but no areas of occlusion. Dissection of the cerebral
hemispheres disclosed no abnormalities. Examination of the brain stem showed well circumscribed
focal areas of old infarction in the ventral aspect of
the base of the mid and lower pons. The largest
measured 0O8 cm x 0O8 cm x 07 cm and was situated along the ventral margin of the pons at the level
of the trigeminal nuclei. Two smaller infacts were
present in the left basis pontis in the area of the left

corticospinal tract.

Numerous histological sections through the brainstem showed that the infarcts were all of recent
onset (compatible with the terminal two week history). The infarcts were well circumscribed and were
limited to the basis pontis where the principal structures destroyed were the ventral and adjacent portions of the medial pontine decussation (decussatio
ventralis pontis) and the stratum superficiale of the
pontine base (fig 2). The ventral nucleus of the pons
(nucleus ventralis pontis) and descending cerebellopontine fibers were also affected. A smaller, separate infarct destroyed medial portions of the left corticospinal tract and the frontopontine tract. Adjacent portions of the stratum profundum pontis were
also involved on the left side. Sections of the basilar
and vertebral arteries showed severe atherosclerosis
with varying degrees of lumenal narrowing; no
occlusions were encountered.
The neuropathological diagnoses were. (1)
infarct, recent, focal, of the pons (basis pontis),
bilateral, (2) atherosclerosis, severe, basilar and vertebral arteries.

Case 3 A 76-year-old black female with a past history of hypertension and atherosclerotic heart disease was admitted to the hospital after she
awakened from a nap and found that she was

224

Liu, Tuhrim, Weinberger, Song, Anderson

right. A CT scan performed without contrast
enhancement revealed an area of decreased density
in the brainstem compatible with an infarction. The
patient eventually succumbed to pneumonia. No
necropsy was performed.
Discussion

Fig 2 Case 2. Section through the pons at the level of the
trigeminal nuclei. Recent infarction destroys the ventral and
medial pontine decussation and the stratum superficiale of
the pontine base. Smaller infarcts are present in the left
corticospinal tract and the stratum profundum pontis
(Kluver stain, x 3).

unsteady on her feet. Examination on admission
revealed a normal mental status. Her speech was
dysarthric. She had a left gaze preference but could
look to her right. Her pupils were 2 mm in diameter
and normally reactive. There was decreased
optokinetic nystagmus to the left. Her tongue deviated to the left on protrusion and there was a left
central facial nerve palsy. There was a left
hemiparesis more marked in the upper extremity
and greater distally than proximally with a total
paralysis of the left hand. Sensory testing revealed
no abnormalities. Deep tendon reflexes were
increased on the left and there was a right extensor
plantar response. Six hours later, she was found to
be obtunded and was observed to have a paralysis of
conjugate gaze to the right and continuous extensor
posturing. She was treated with 16 mg dexamethasone qd. The following morning she was
quadraplegic, unable to speak but able to follow
commands with vertical eye movements. The eyes
were deviated to the left, but could still move to the

The locked-in state may develop from infarction in
the rostral and ventral pons secondary to thrombosis
or occlusion of the basilar artery.'-5. The prognosis
is poor, with 31 of 34 reported cases dying within a
few weeks of onset. Three patients survived for over
two years.4 13 Review of the clinical presentation in
28 necropsy cases revealed that 25 were due to
ischaemic vascular disease. Eleven patients
developed the locked-in state acutely while 14 had
premonitory symptoms of brain stem infarction.
Eleven of these 14 patients had hemisensory or
hemimotor deficits as part of their preliminary
symptoms. (table).
The three cases reported here presented with mild
hemisensory or hemimotor deficits involving the
ipsilateral face and extremities. They were initially
felt to have cerebral infarctions, but the finding of
dysarthria suggested a brainstem localisation. All
three had symptoms similar to those described with
"lacunar" infarcts such as pure motor hemiparesis'6
or pure hemisensory deficit.'7 Three of nine necropsied cases described by Fisher and Curry with pure
motor hemiparesis had concomitant dysarthria and
were found to have pontine infarcts.'6 Two of the
three had rapid progression and died shortly after
onset. The patients with cerebral lesions had no
dysarthria, and recovered from their neurologic
deficits, but succumbed to other causes.
Strokes in the vertebrobasilar circulation may
have a good prognosis, with full recovery occurring
in 55% of cases whose symptoms persist for at least
2 weeks.'8 Patients with severe hemimotor deficits
have a poorer prognosis.'9 This deterioration may be
more predominant when the lesion produces a contralateral hemimotor or hemisensory deficit involving the face on the same side as the extremities.
These lesions may be difficult to discriminate from
cerebral infarcts, especially when there is a
homonymous hemianopsia due to compromise of
flow in the posterior cerebral circulation, as in Case
1. A pontine lesion may be indicated when there is
concurrent dysarthria or paresis of conjugate gaze
with the eyes deviated towards the paresis.
It is important to recognise that brainstem infarction with symptoms and signs referrable to the rostral pons may lead to more severe deficits. Since
most infarctions in this region are secondary to
thrombotic occlusive disease of the basilar artery

225

Premonitory symptoms of stroke in evolution to the locked-in state
Table Presenting symptoms and anatomical pathology ofthe locked-in state
Presenting symptom
Hemiparesis including ipsilateral face

Hemiparesis with dysarthria

Hemiparesis with dysarthria and ataxia

Number

Reference

Anatomic pathology

Vascular Pathology

2
2
1
1
1

(1, 2)
(3

Basilar occlusion
Basilar occlusion
Vertebral occlusion

(4)
(13)
(14)

Ventral pontine infarct
Ventral pontine infarct
Ventral pontine infarct
Pontine infarct on CT
Infarct pons, cerebral
peduncle
Infarct pons, midbrain
medulla
Ventral pontine infarct
Ventral pontine infarct
Ventral pontine infarct
Infarct pons, midbrain,
medulla
Infarct upper pons and
midbrain
Ventral pontine infarct
Pontine infarct involving
Cerebral peduncles
Ventral pontine infarct
Pontine hemorrhage
No post-mortem
Ventral pontine infarct
No post-mortem
No post-mortem
Ventral pontine infarct

(15)

Reticulum cell sarcoma, pons

4
Case 3
(5)

Hemiparesis with diplopia and dysarthria 1

(6)

Hemisensory syndrome with dysarthria

2
1
1

Case 1 & 2

1
1

(6)
(7)

5
1

(2, 8-11)
(12)

1
1
3
4
2
1
1
1
1

(6)

Crossed sensory syndrome
Crossed motor syndrome with sensory
loss and dysarthria
Truncal ataxia
Acute locked-in state

No information
Post head trauma
Post surgical resection of
acoustic neuroma

Progressive quadriparesis

(3)
3)

(6)

(6)
(4)

(table), anticoagulant therapy may be indicated in
these patients when the initial deficit is mild. Anticoagulant therapy has been shown to be of some
benefit in several controlled trials on patients with
brainstem stroke in evolution.20 It may prevent the
occurrence of severe neurologic disorders such as
the locked-in state in patients presenting with
hemisensory or hemimotor findings and dysarthria if
this is recognised as an ischaemic event in the contralateral rostral pons.

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