The Localization of Lesions Causing
Coma
Dr. Mohammed Alanazy
Outline
• Coma, Akinetic Mutism, and Locked-In Syndrome
• Anatomic Substrate of Alertness
• Signs with Localizing Value in Coma
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Respiratory Patterns
Temperature Changes
The Pupils
Eye Movements
Motor Activity of the Body and Limbs
• Clinical Presentations of Coma-Inducing Lesions Depending on their
Location
– Metabolic Encephalopathy (Diffuse Brain Dysfunction)
– Supratentorial Structural Lesions
– Subtentorial Structural Lesions
• Psychogenic Unresponsiveness
Coma, Akinetic Mutism, and
Locked-In Syndrome
• Akinetic mutism : refers to a state in which the patient,
although seemingly awake, remains silent and motionless. Only the
eyes dart in the direction of moving objects, such as the examiner
approaching the patient's bed. The examiner, attempting to
converse with a patient in this state, gets the distinct impression of
failing to draw the patient's attention and interest. Despite the lack of
movement, there are few signs indicative of damage to the
descending motor pathways.
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frontal release signs, may be present..
• If a history is available, akinetic mutism can be
usually distinguished from psychogenic (often
catatonic) unresponsiveness.
• Signs of frontal release or corticospinal tract
damage favor the diagnosis of akinetic mutism.
• In the catatonic patient, the EEG is normal (often
desynchronized, with low-voltage fast activity),
but in the patient with akinetic mutism the EEG
often shows slow-wave abnormalities.
• Localization:
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bilateral frontal region (anterior cingulate gyri),
the diencephalo-mesencephalic reticular formation,
the globus pallidus, or
the hypothalamus .
• Common causes :
– anoxia, head trauma, cerebral infarction, severe acute
hydrocephalus, and direct compression by tumors , air embolism
or end-stage degenerative or infectious brain disorders, such as
Creutzfeldt-Jakob disease
– Metabolic or ictal disorders : transient disorder of alertness
similar to akinetic mutism
– A syndrome of transient mutism and relative akinesia may occur
a few days after midline cerebellar or fourth ventricular surgery
• Hyperkinetic mutism, with continuous bilateral ballism
and dystonia, has been described in a diabetic with
multiple subcortical and cortical infarcts
Vegetative state
• a chronic neurologic condition characterized by lack of awareness of
self and external stimuli
• accompanied by sleep-wake cycles,
• preservation of vital vegetative functions, such as cardiac function,
respiration, and maintenance of blood pressure.
• no evidence of sustained, reproducible, purposeful, or voluntary
behavioral responses to visual, auditory, tactile, or noxious stimuli
• show no evidence of language comprehension or expression
• have bowel and bladder incontinence
• variably preserved cranial nerve and spinal reflexes.
• Persistent vegetative state is defined as a vegetative
state lasting for at least 1 month
• Recovery of consciousness from a posttraumatic
persistent vegetative state is unlikely after 12 months in
adults and children.
• Recovery from a nontraumatic persistent vegetative
state after 3 months is exceedingly rare in both adults
and children.
locked-in syndrome
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the patient is mute and motionless (de-efferented) but remains awake, alert,
aware of self, and capable of perceiving sensory stimuli.
Horizontal eye movements are often impaired due to the involvement of the
PPRF
vertical eye movements or eyelid movements are preserved .
The EEG reflects the patient's state of wakefulness.
Localization:
– lesions involve the descending motor pathways bilaterally in the basis pontis but
spare the more dorsal reticular formation
– Bilateral ventral midbrain lesions
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Causes:
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basilar artery thrombosis with ventral pontine infarction
pontine hemorrhage
tumor
central pontine myelinolysis (osmotic demyelination syndrome)
tentorial herniation
Guillain-Barre syndrome or myasthenia gravis may rarely cause this
syndrome.
Outline
• Coma, Akinetic Mutism, and Locked-In Syndrome
• Anatomic Substrate of Alertness
• Signs with Localizing Value in Coma
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Respiratory Patterns
Temperature Changes
The Pupils
Eye Movements
Motor Activity of the Body and Limbs
• Clinical Presentations of Coma-Inducing Lesions Depending on their
Location
– Metabolic Encephalopathy (Diffuse Brain Dysfunction)
– Supratentorial Structural Lesions
– Subtentorial Structural Lesions
• Psychogenic Unresponsiveness
Anatomic Substrate of Alertness
• the maintenance of consciousness depends on
interaction between the ascending reticular activating
system (ARAS) and the cerebral hemispheres
• the ARAS lies in the paramedian tegmental region
of the posterior portion of the pons and midbrain .
• It is a complex polysynaptic fiber system that
extends from the superior half of the pons through
the midbrain to the posterior portion of the
hypothalamus and to the thalamic reticular
formation
• The thalamus is the source of diffuse
thalamocortical projections that regulate and
coordinate cortical activity
• Sedative drugs act, at least in part, by interfering
with the synaptic network of the ARAS, which is
played on by sensory stimuli.
• Bilateral cerebral hemispheric lesions may cause transient coma,
particularly when they involve the mesial frontal region.
• Large unilateral lesions of the dominant hemisphere may
occasionally cause transient unresponsiveness, even in the
absence of a mass effect .
• posterior hypothalamic lesions induce prolonged hypersomnia.
• Acute bilateral damage of the paraventricular thalamic nuclei is
attended by transient unresponsiveness, followed, when the lesions
are large, by severe amnestic dementia .
Outline
• Coma, Akinetic Mutism, and Locked-In Syndrome
• Anatomic Substrate of Alertness
• Signs with Localizing Value in Coma
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Respiratory Patterns
Temperature Changes
The Pupils
Eye Movements
Motor Activity of the Body and Limbs
• Clinical Presentations of Coma-Inducing Lesions Depending on their
Location
– Metabolic Encephalopathy (Diffuse Brain Dysfunction)
– Supratentorial Structural Lesions
– Subtentorial Structural Lesions
• Psychogenic Unresponsiveness
Respiratory Patterns
Cheyne-Stokes respiration
– denotes a cyclic pattern of alternating hyperpnea and
apnea.
– a bilateral hemispheric or diencephalic insult
– may indicate incipient transtentorial herniation
– CHF,COPD,OSA,Uremia.
Hyperventilation
– injury in the pontine or midbrain tegmentum;
– respiratory failure, hemodynamic shock, fever, sepsis,
metabolic disarray, and psychiatric disease.
Apneustic breathing
– prolonged pause at the end of inspiration
– lateral tegmentum of the lower half of the pons.
Cluster breathing
– Periodic respirations that are irregular in frequency
and amplitude with variable pauses between clusters
of breaths
– lower pontine tegmental lesion
Ataxic breathing
– is irregular in both rate and tidal volume
– suggests damage to the medulla.
Temperature Changes
• caused by hypothalamic dysfunction
• Neurogenic hyperthermia has also been
described with pontine tegmental lesions
The Pupils
1. Sleep or bilateral diencephalic dysfunction (metabolic coma) is
accompanied by small pupils that react well to light (diencephalic
pupils).
2. Unilateral hypothalamic damage induces miosis and anhidrosis on
the side of the body ipsilateral to the lesion.
3. Midbrain lesions
1. Tectal or pretectal lesions affecting the posterior commissure
1. abolish the light reflex,
2. the pupils are midsized or slightly large,
3. may show spontaneous oscillations in size (hippus) and become larger when
the neck is pinched (ciliospinal reflex).
2. Tegmental lesions, which involve the third nerve nucleus, nonuniform
paresis or paralysis of the pupil sphincter may cause irregular
constriction of the sphincter of the iris, with a resultant pear-shaped
pupil or displacement of the pupil to one side (midbrain corectopia) .
The pupils, often unequal, tend to be midsized and lack light or
ciliospinal responses.
4. Pontine tegmental lesions cause small pupils due to interruption of
the descending sympathetic pathways.
5. Lateral pontine, lateral medullary, and ventrolateral cervical cord
lesions produce an ipsilateral Horner syndrome.
6. Oculomotor nerve compression by uncal herniation affect pupillary
function earlier and more noticeably than the extrinsic eye
movements . The light reflex is sluggish or absent, and, the pupil
becomes widely dilated owing to sparing of the sympathetic
pathways (Hutchinson's pupil).
7. Posterior communicating artery aneurysms can compress the third
nerve and a massive subarachnoid hemorrhage may result in coma.
Fixed pupils are not necessarily a sign of irreversible coma. In a series of 40
patients with fixed pupils, 25% of them made a functional recovery . None of
these patients recovered after more than 6 hours with fixed pupils.
Eye Movements
• Roving eye movements
– the eyelids are closed, and the eyes, slightly
divergent, drift slowly from side to side
– the brainstem is intact
– cannot be voluntarily executed and are therefore
incompatible with the diagnosis of pseudocoma.
In metabolic coma, the pupils may still react when eye
movements cannot be elicited.
• eyes-open coma
– The eyelids may remain tonically retracted because of
failure of levator inhibition in some cases of pontine
infarction.
• Short-cycle periodic alternating gaze
(ping-pong gaze),
– roving of the eyes from one extreme of
horizontal gaze to the other and back, with
each oscillating cycle taking 2.5 to 8 seconds
– This finding usually indicates bilateral cerebral
damage (e.g., bilateral cerebral infarcts) with
an intact brainstem, but it has also been
described with posterior fossa hemorrhage,
basal ganglia infarcts, hydrocephalus, ….
– This disorder of ocular motility had no
prognostic value .
• Repetitive divergence
– the eyes are in midposition or slightly
divergent at rest. They then slowly deviate
out, become fully deviated for a brief period,
and then rapidly return to the primary position
before repeating the cycle. These motions are
synchronous in both eyes.
– is rarely seen in patients with coma from
metabolic encephalopathy (e.g., hepatic
encephalopathy)
• Nystagmoid jerking of a single eye, in a vertical,
horizontal, or rotatory fashion, may occur with mid- to
lower pontine damage.
• status epilepticus without appendicular motor
manifestations, due to anoxia, may result in brisk, smallamplitude, mainly vertical (occasionally horizontal) eye
movements detectable by passive lid elevation
• Ocular bobbing
• intermittent, often conjugate, brisk, bilateral downward movement of
the eyes with slow return to midposition
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pontine lesions
extra-axial posterior fossa masses
diffuse encephalitis
Creutzfeldt-Jakob disease
toxic-metabolic encephalopathies (e.g., acute organophosphate
poisoning)
• Typical ocular bobbing,
– associated with preserved horizontal eye movements,
– specific but not pathognomonic of acute pontine injury,
• Atypical ocular bobbing,
– associated with absent horizontal eye movements, non-localizing
• Monocular bobbing (paretic bobbing), may occur if there is a
coexistent unilateral fascicular oculomotor nerve palsy
• Inverse ocular bobbing (ocular dipping )
– consists of a slow-downward eye movement
with fast return to midposition
– occur in anoxic coma or after prolonged
status epilepticus
– It probably reflects diffuse brain dysfunction
rather than a single structural lesion
– brainstem horizontal gaze reflexes are usually
intact.
• Reverse ocular bobbing
– fast-upward eye movement with a slow return to
midposition,
– occur in patients with metabolic encephalopathy, viral
encephalitis, or pontine hemorrhage .
• Reverse ocular dipping
– slow-upward eye movements followed by fast return
to midposition
– metabolic or viral encephalopathy (i.e., diffuse
cerebral dysfunction) .
– pontine infarction (the patient had a one-and-a-half
syndrome)
• Pretectal pseudobobbing
• has been described with acute hydrocephalus.
• arrhythmic, repetitive downward and inward (V pattern) eye
movements at a rate ranging from 1 per 3 seconds to 2 per second
and an amplitude of 1/5 to 1/2 of the full voluntary range.
• These movements may be mistaken for ocular bobbing, but their V
pattern, their faster rate, and their pretectal rather than pontineassociated signs distinguished them from true pontine bobbing.
• may have abnormal pupillary light reactions, intact horizontal eye
movements, openand often retracted eyelids, a blink frequently
preceding each eye movement, and a mute or stuporous rather than
a comatose state.
• Vertical ocular myoclonus
– pendular, vertical isolated movements of the eyes
noted
– patients either locked-in or comatose after severe
pontine strokes
– other rhythmic body movements at a similar
frequency occur after a 6-week to 9-month delay.
– associated with palatal myoclonus (palatal tremor),
with which they share a common mechanism
Abnormalities of Lateral Gaze
1. Conjugate Gaze
When both eyes remain deviated toward the same side in a
comatose patient,
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Hemispheric lesion, the eyes look toward the lesion (away from the
hemiparetic side)
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A seizure originating in the frontal or occipital lobes may cause
deviation of the eyes and head away from the lesion.
• wrong-way eyes
– forced deviation of the eyes to the side contralateral to the lesion
– Thalamic and, rarely, basal ganglionic lesions, almost always
hemorrhagic,
– Very rarely, frontal-perisylvian lesions
• Unilateral lesions affecting the tegmentum of the lower pons cause a
horizontal gaze palsy toward the side of the lesion so that the eyes
look toward the hemiparetic side.
– Neither the oculocephalic maneuver nor caloric testing
overcomes a pontine gaze palsy.
• Coma due to toxic substances is often accompanied by impaired
conjugate eye movements, horizontal as well as vertical (
Wernicke's encephalopathy)
2. Disconjugate Gaze
• Isolated failure of ocular adduction, in the
absence of pupillary changes and with normal
vertical eye movements (elicited by
oculocephalic or oculovestibular reflexes),
• a lesion of the MLF in the upper pons ipsilateral
to the eye that fails to adduct.
• MLF involvement is commonly bilateral in
comatose patients.
• Latent strabismus may become apparent when
the level of alertness is mildly impaired but
disappears in deep coma.
Abnormalities of Vertical Gaze
• Disconjugate vertical gaze in the resting position (skew
deviation)
– the brainstem, with increased intracranial pressure, or with
hepatic coma
• bilateral midbrain tectal damage: paresis of upward gaze
• thalamic hemorrhage Tonic downward deviation of the
eyes, often accompanied by convergence, (pressure on
the dorsal mesencephalon) .
• Sustained upgaze has been reported with severe anoxic
encephalopathy and with phenothiazine intoxication.
• Downward gaze is preferentially affected
by bilateral lesions of the superomedial
perirubral region
• Large midbrain tegmental lesions abolish
vertical gaze.
Corneal Reflex
• The corneal reflex has a higher threshold in comatose
patients.
• decreased corneal sensitivity
– cranial nerve V lesions, ipsilateral lateral pontomedullary lesions,
or contralateral parietal lesions
• impaired eye closure (as with cranial nerve VII lesions
and low pontine lesions).
– the stimulus may induce deviation of the jaw to the opposite side
(corneopterygoid reflex),
– given an intact upper pons and midbrain, the eyes may roll
upward (Bell's phenomenon)
Motor Activity of the Body and Limbs
• Rarely is a metabolic coma (notably hypoglycemic)
accompanied by hemiparesis
• decorticate and decerebrate rigidity, are often produced
by metabolic disorders
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Flexor (“decorticate”) posturing
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Extensor (“decerebrate”) posturing
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Flexion and adduction of arms and wrists
with
extension of lower extremities;
it suggests hemispheric or thalamic damage,
with sparing of structures below the
diencephalons
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adduction, extension,and pronation of the
upper extremities
and extension of the lower extremities;
It is indicative of injury to the caudal
diencephalon, midbrain, or pons
Severe metabolic (e.g., anoxic) disorders
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• Abnormal extension of the arms with weak flexion of the legs usually indicates
damage of the pontine tegmentum
• With even lower lesions involving the medulla, total flaccidity ensues
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• Flaccidity in a critically ill patient can also be produced by a polyneuropathy/
myopathy
Outline
• Coma, Akinetic Mutism, and Locked-In Syndrome
• Anatomic Substrate of Alertness
• Signs with Localizing Value in Coma
–
–
–
–
–
Respiratory Patterns
Temperature Changes
The Pupils
Eye Movements
Motor Activity of the Body and Limbs
• Clinical Presentations of Coma-Inducing Lesions Depending on their
Location
– Metabolic Encephalopathy (Diffuse Brain Dysfunction)
– Supratentorial Structural Lesions
– Subtentorial Structural Lesions
• Psychogenic Unresponsiveness
Metabolic Encephalopathy (Diffuse Brain
Dysfunction)
• carbon monoxide poisoning causes pallidal necrosis in
addition to the widespread cortical damage
• Functions subserved by complex polysynaptic pathways
are affected earlier by metabolic disturbances than those
mediated by a few neurons.
• Therefore, higher cortical functions and attention
succumb early to metabolic insults, whereas the pupillary
light reflex remains
• Asymmetric motor findings speak against the diagnosis
of metabolic encephalopathy
• Exceptions:
• downward deviation of the eyes may be occasionally
associated with hepatic encephalopathy
• hemiparesis with hypoglycemia.
• ethylene glycol, produce focal brain injuries with the
corresponding neurologic localizing findings
• Focal seizures are common in metabolic
encephalopathies, particularly those coursing with the
breakdown of the blood-brain barrier, such as eclampsia,
malignant hypertension, and acute intermittent porphyria
• Toxic-metabolic disorders often induce abnormal
movements (tremor, asterixis, myoclonus, and seizures)
that seldom accompany focal structural lesions of the
brain.
• Unilateral asterixis may appear when a toxic encephalopathy
coexists with a structural lesion in:
– contralateral to lesions of the mesencephalon, ventrolateral thalamus, primary
motor cortex, or parietal lobe
– ipsilateral to lesions of the pons or medulla
• Episodes of lapses of postural control by the reticular formation may
be responsible for midbrain asterixis.
• Occasionally, bilateral asterixis may occur with bilateral lesions of
the midpons or with bilateral mesencephalic lesions.
• Multifocal myoclonus
– sudden, nonrhythmic twitching that affects first one muscle, then
another, without any specific pattern except a tendency to
involve the facial and proximal limb musculature.
• The causes :
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uremic
hyperosmolar-hyperglycemic encephalopathy,
carbon dioxide narcosis,
a large dose of intravenous penicillin
• Generalized myoclonus,
• mainly involves the axial musculature, which contracts suddenly,
making the patient jump with a certain periodicity
• It may also appear as irregular brief jerks in both face and limbs.
• The myoclonus is often stimulus sensitive
• is most prominent in the first postresuscitation day and tends to
abate spontaneously in subsequent days.
• The patients often have a burst-suppression pattern on EEGs and
cerebral edema or infarcts on CT scan or MRI.
• Severe anoxic cortical and brainstem damage are the most common
pathologic correlates of generalized myoclonus (also called
myoclonic status), which carries a poor prognosis
Supratentorial Structural Lesions
• Lateral Herniation
lateral extracerebral or temporal lobe masses
push the mesial temporal lobe (uncus anteriorly, parahippocampal gyrus posteriorly) between
the ipsilateral aspect of the midbrain and the free edge of the tentorium
compresses the third cranial nerve and posterior cerebral artery
the ipsilateral pupil becomes progressively dilated and responds sluggishly to light
a hemorrhagic mesial occipital infarct
pushes the midbrain against the rigid edge of the dura on the opposite side of the tentorial opening
carves out a notch (Kernohan's notch) in the lateral aspect of the midbrain, interrupting the cerebral
peduncle (particularly the fibers that project to the leg) on the side opposite the original temporal
lobe lesion
hemiparesis ipsilateral to the original lesion (Kernohan's notch phenomenon)
a false localizing sign
tearing of the paramedian midbrain perforating vessels infarction and hemorrhages (Duret's
hemorrhages)  the sympathetic pathway is damaged in the midbrain  pupil becomes midsize
and unresponsive.
Oculomotor paresis appears first in the eye originally involved and shortly afterward in the other eye.
Clinical Findings in Uncal Herniation Syndrome
• Central Herniation
frontal, parietal, or occipital masses
the supratentorial pressure increases,
first compress the diencephalon
shifts downward and buckles over the midbrain.
Subsequent flattening of the midbrain and pons in the rostrocaudal direction
causes elongation and rupture of the paramedian perforating arteries
infarction and hemorrhages (Duret's) in the tegmentum of the midbrain (first) and pons
(afterward)
Paralleling the pathologic changes of central herniation, the clinical picture reflects an
orderly rostrocaudal progression of brainstem damage.
Early Diencephalic Stage
Impaired attention and somnolence
Roving eye
movements
Late Diencephalic Stage
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At this stage the patient cannot be aroused.
Roving eye movements have disappeared,
tectal dysfunction may result in restriction of upward gaze. Light painful stimuli fail to
elicit any response
Proper diagnosis and treatment at this stage of the syndrome of central herniation
may still result in recovery of neurologic function. Once the clinical picture evolves
into the next stage (caused by hemorrhages and infarction of the midbrain
tegmentum), the prognosis is very poor, except in children.
Midbrain- Upper Pons Stage
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Temperature oscillations are common, and an occasional patient may develop diabetes insipidus
because of stretching of the median eminence of the hypothalamus.
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The pupils become midsized, unequal, and irregular, often pear-shaped and eccentric.
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The doll's eye maneuver and caloric testing elicit restricted or no vertical eye movements.
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The eyes often move disconjugately in both the horizontal and the vertical planes.
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Bilateral impairment of adduction may reflect dysfunction of both third nerve nuclei, of the medial
longitudinal fasciculi, or both.
Lower Pontine Stage
Medullary Stage
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ataxic breathing soon gives way to apnea.
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The blood pressure drops, and the pulse becomes irregular
Subtentorial Structural Lesions
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Early in the clinical course, occipital headache, vomiting, and ataxia are usually
prominent
Lesions that compress the upper brainstem
may cause upward transtentorial herniation of the tectum of the midbrain and of the
anterior cerebellar lobule  giving rise to signs of midbrain dysfunction with coma,  hyperventilation, fixed pupils, and vertical ophthalmoplegia.
Lower lesions impinge on the pontine tegmentum
– somnolence,
– pinpoint pupils that react briskly to light,
– oculoparetic nystagmus on lateral gaze,
– truncal ataxia.
– Appendicular ataxia may be so mild as to pass unnoticed.
As pontine function becomes worse
– horizontal gaze disappears and cannot be elicited with the doll's eye maneuver
or caloric testing, whereas impairment of vertical eye movements clearly lags
behind.
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lesions that impinge on the medulla,
respiratory ataxia evolving to apnea
circulatory abnormalities precede changes in the level of alertness.
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The medulla is particularly resistant to infarction, spontaneous hemorrhages, and
even traumatic lesions.
However, it is preferentially affected in Listeria monocytogenes rhombencephalitis
and in Leigh's disease
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Psychogenic Unresponsiveness
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The patient may hold the eyes forcibly closed and resist eyelid opening
or may keep the eyes open in a fixed stare, interrupted by quick blinks.
The pupils, which are of normal size and position, react to light unless a cycloplegic
drug has been instilled into them.
The doll's eye maneuver elicits random or no eye movements.
Caloric testing is more helpful because it gives rise to classic vestibular nystagmus
with a quick component that requires activity of the frontal eye fields. This quick
component is, conversely, absent in comatose patients.
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Muscle tone and reflexes are normal.
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The patient may hyperventilate or breathe normally
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Psychogenic unresponsiveness often recurs and as such is frequently misdiagnosed
as an epileptic or migranous disorder.
.
• Thank you