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대한평형의학회지 제 4 권 1 호 2005 ; 131-141
Cerebellar Control of Eye Movements
David Zee
The Johns Hopkins University, USA
Function of eye movements
The dominance of the
fovea
•Serve the needs of
vision, and specifically
those of the fovea
where spatial acuity is
best.
•Bring images onto
the fovea (saccades
and vergence)
•Keep images still on
the fovea, for best
spatial resolution
(vestibular, pursuit and
vergence)
Courtesy, C.Kennard
Cerebellum and eye movements:
Some basic principles
→ Cortex versus deep nuclei (vestibular nucleus)
→ Direct (via deep nuclei) and indirect (via
cortex to deep nuclei) pathways through the
cerebellum
→ Purkinje cells inhibit their target neurons
→ Complex spike (climbing fiber) and simple spike
(mossy fibers/granule cells) of P-cells discharge
reciprocally
→Immediate/on line vs. long-term/adaptive role
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Cerebellar Control of Eye Movements
Cerebellar flocculus and paraflocculus (tonsils)
An anatomical – functional tour of
the cerebellum
•Flocculus/paraflocculus
•Nodulus
•Dorsal (oculomotor) vermis
Flocculus
Paraflocculus
Downbeat, gaze-evoked and rebound
nystagmus in cerebellar atrophy
Gaze-evoked nystagmus
First description of gaze-evoked nystagmus in cerebellar
disease
Rebound
nystagmus
Calcium channel on chromosome 19
FHM
EA-2
SCA-6
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David Zee
Calcium channels and the cerebellum
Rhesus Monkey –
Flocculus/Paraflocculus
• HYPOTHESIS -- Hyperventilation
changes pH and free calcium, impairs
calcium-channel, leads to further P-cell
malfunction in vestibulocerebellum, and
increases down-beat nystagmus.
• Diamox (changes blood pH) potentially
may prevent long-term P-cell toxicity
and delay or prevent progression in
cerebellar ataxia??
CN VIII
Flocculus
Paraflocculus
Downbeat, gaze-evoked, rebound
nystagmus in monkey with removal
of flocculus and paraflocculus
Impaired smooth pursuit in monkey with
removal of flocculus and paraflocculus
Pre
Post
Velocity-increasing slow phase
A simple control systems model of control of gaze-holding
by the flocculus
• Inherently poor brain
stem neural gazeholding network
(MVN,NPH).
• Flocculus improves its
function by a positive
feedback loop (‘k’).
• Too little feedback,
poor gaze holding.
Blink
• Too much feedback,
instability and runaway
slow phases.
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Cerebellar Control of Eye Movements
Arnold-Chiari malformation
• Valsalva-induced vertigo, headache, or facial or neck
pain
• Cranial nerves IX and X (hoarseness and dysphagia)
• Nystagmus
–
–
–
–
–
–
–
Downbeat, worse on lateral gaze and with convergence
Positional downbeat
Gaze-evoked
Rebound
Centripetal (on eccentric gaze, nystagmus beats inward)
Periodic alternating
Divergence (slow phases adduct, quick phases abduct)
• Alternating skew deviation (abducting eye usually higher)
• Postural dysequilibrium
• NOTE: Decompression often leads to improvement in eye
movement disturbances albeit it may take some time.
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Downbeat nystagmus in adults
• Paraneoplastic syndrome (anti-yo in women (gyn tumors),
anti-hu, antigad, antima/ta. Note anti-ri is associated
with opsoclonus)
• Lithium, carbamazepine, amiodorone
• Cerebellar degeneration
• Cranio-cervical junction anomalies
• Wernicke's encephalopathy (often converts to upbeat with
convergence or vice versa)
• TREATMENT – 3,4 diaminopyridine or 4 aminopyridine.
Note also some evidence these work in upbeat nystagmus
and in EA2 (episodic ataxia type 2). Other choices,
though less consistently helpful, include clonazepam and
baclofen.
David Zee
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Cerebellar Control of Eye Movements
VOR learning in Purkinje Cells
Periodic Alternating
Nystagmus (PAN)
Null every two minutes
Vestib input
(head)
Visual input
(image slip)
Ito, NatureNS
Rotation at a constant
speed in darkness
Anatomical Locus of PAN
Pathophysiology of PAN:
Normal vestibular responses gone awry
Nodulus
Cupula decay
Velocity Storage Mechanism
Nystagmus outlasts the displacement of the
cupula. ‘Velocity storage’ perseverates
peripheral canal signals and so improves the
‘low-frequency’ response of the VOR.
Increases VOR duration.
POTENTIAL FOR INSTABILITY
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David Zee
Pathophysiology of PAN:
Normal vestibular responses gone awry
Onset head
rotation
Reversal Phase
adaptation to
sustained nystagmus.
POTENTIAL FOR REVERSING
NYSTAGMUS
PAN: Pathogenesis and Treatment
• Two key normal mechanisms
– Central velocity storage mechanism located within the
vestibular nuclei that improves the ability of the
vestibular system to respond to low-frequency head
motion by perseverating peripheral vestibular signals.
– Adaptation mechanism that acts to null any sustained
unidirectional nystagmus (which in natural
circumstances is always due to a lesion)
• In PAN, instability in velocity storage is produced by loss
of (gaba-mediated) inhibition from the Purkinje cells of
the nodulus onto the vestibular nuclei.
• Short-term adaptation (which is working normally) causes
reversals of nystagmus leading to sustained oscillation.
• Baclofen (GABA-b) provides the missing inhibition and
stops the nystagmus.
– Usually need only 10 mg PO TID.
– Avoid precipitous discontinuation.
– Does not work as well in congenital PAN.
Oculomotor Vermis
(lobules VI and VII) and
the Fastigial Oculomotor
Region (FOR)
VI and VII
FOR
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Cerebellar Control of Eye Movements
Wallenberg’s Syndrome – PICA distribution infarct
involving the dorsolateral medulla
Restiform body (ICP)
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David Zee
Fastigial nucleus facilitates
contralateral saccades
Purkinje cells inhibit deep
nuclei
Lateropulsion of saccades: A
FUNCTIONAL lesion of the fastigial
nucleus (FOR) in Wallenberg’s
syndrome
Complex and simplespike discharge of Pcells are inversely
related
Lesion interrupts
climbing fiber input
to dorsal vermis
Simple-spike
(inhibitory) discharge
of P-cells increases
Fastigial nucleus (FOR)
activity decreases -functional lesion
Saccades overshoot
toward, undershoot
away, from the lesion
SOS
Occlusion of Posterior Inferior Cerebellar Artery
(PICA) : Vestibular and ocular motor findings
• Otolith syndrome (involvement of caudal vestibular nuclei)
– Skew deviation -- eye lower on the side of the lesion
– Head tilt -- to the side of the lesion
– Ocular counterroll -- both eyes roll (top of eye)
toward the side of the lesion
– Disordered perceptions of verticality
– Pulsion of the body (vestibulospinal) toward the side of
lesion
• Saccade syndrome (interruption of climbing fibers (ICP)
causing a functional inhibition of ipsilateral fastigial
nucleus)
– Lateropulsion of saccades (saccades overshoot toward
(ipsipulsion) and undershoot away, from lesion side)
– Vertical saccades deviate toward the side of the
lesion
– Under closed lids, deviation of the eyes toward the
lesion side
Short-term saccade adaptation paradigm – Double
step of position
0 deg
Decreasing paradigm -- Target
jumps back after eye begins
moving simulating overshoot
dysmetria. Saccade amplitude
must be decreased.
Target
Increasing paradigm -- Target
jumps forward after eye
begins moving simulating
undershoot dysmetria.
Saccade amplitude must be
increased.
200ms
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Cerebellar Control of Eye Movements
EXO
2
0
0min
POST 5min
10min
Horizontal
alignment
-2
M1
20min
30min
Prelesion
Adaptation
-4
Cerebellum and the Control of Eye Movements
-6
-8
ESO
Phoria Adaptation
10 diopter base out
prism in front of one
eye to produce
sustained motor
fusion for 30
minutes.
Phoria (eye alignment
without disparity)
measured every 10
minutes (monocular
viewing).
140
deg
-10
2
0
Postlesion
Decreased
Adaptation
-2
M2
PRE
-4
POST
-6
-8
-10
2
0
-2
M3
-4
-6
-8
-10
Prelesion
Adaptation
→ Specific anatomical / functional relationships
→ Flocculus/paraflocculus – stabilization of images
on fovea – brief vestibular responses, pursuit and
gaze-holding
→ Nodulus – modulation of sustained vestibular
responses.
→ Dorsal vermis / Fastigial Nucleus – saccades,
initiation of pursuit, eye alignment (‘open-loop’
movements).
David Zee
Summary
• Cerebellum has a major role in control of ocular
motility:
– ‘On-line’, immediate functions, including gaze-holding,
pursuit, saccade accuracy and vestibulo-ocular reflex
amplitude and direction.
– Long-term, motor learning to keep eye movements
accurate and maintain optimal visuo-motor
performance.
• Cerebellum has a major role in binocular eye
movement control:
– Static eye alignment
– Dynamic vergence characteristics
– Phoria adaptation
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