Cerebellar Ataxia Pathophysiology and Rehabilitation

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Clinical Rehabilitation
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DOI: 10.1177/0269215510382495
2011 25: 195 Clin Rehabil
Jon Marsden and Chris Harris
Cerebellar ataxia: pathophysiology and rehabilitation
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Clinical Rehabilitation 2011; 25: 195216
Rehabilitation in practice
Cerebellar ataxia: pathophysiology and rehabilitation
Jon Marsden School of Health Professions, Faculty of Health, University of Plymouth and
Chris Harris School of Psychology, Faculty of Science, University of Plymouth, Plymouth, UK
This series of articles for rehabilitation in practice aims to cover a knowledge
element of the rehabilitation medicine curriculum. Nevertheless they are intended
to be of interest to a multidisciplinary audience. The competency addressed in this
article is The trainee consistently demonstrates a knowledge of management
approaches for specific impairments including spasticity, ataxia.
Introduction
Cerebellar dysfunction may result in significant
functional difficulties with upper and lower limb
movement, oculo-motor control, balance and
walking. Such difficulties can affect employability,
increase carer burden and reduce a persons per-
ceived quality of life.
1
The economic burden of
people with spinocerebellar ataxia is estimated to
be around E18 776 per annum.
1
This article
will review the signs and symptoms and patho-
physiology of cerebellar ataxia, highlighting the
theoretical basis of current non-surgical and non-
pharmacological rehabilitation techniques.
Search strategy and selection criteria
References for this review were identified from a
search of PubMed (from 1966 to 2009) and the
Cochrane Library with the search terms cerebel-
lum or cerebellar and ataxia or tremor and phys-
iology or pathophysiology or rehabilitation
or therapy). Articles were further identified through
searches of reference lists in identified papers.
Anatomy
Gross anatomy
Cerebellar ataxia arises due damage or dysfunc-
tion affecting the cerebellum and/or its input/
output pathways. In a rostro-caudal direction the
cerebellum can be divided into three lobes: ante-
rior, posterior and flocculo-nodular. Some of these
may take the brunt of certain pathologies. The
anterior lobe, for example, is particularly affected
in alcoholic cerebellar degeneration.
2
The cerebel-
lum connects to the medulla, pons and midbrain
via the inferior (restiform body), middle and supe-
rior cerebellar peduncles through which pass affer-
ent and efferent pathways.
Functionally, the cerebellum is organized in
a medio-lateral fashion with different areas of
the cerebellum having a distinct anatomical
Address for correspondence: Professor Jon Marsden, School of
Health Professions, Peninsula Allied Health Centre, Derriford
Road, University of Plymouth PL6 8BH, UK.
e-mail: Jonathan.marsden@plymouth.ac.uk
The Author(s), 2011.
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inputoutput relationship resulting in a specific
lesionsymptom relationship.
35
The midline
vermis connects to the fastigial deep cerebellar
nucleus, while the flocculonodular lobe is con-
nected with the vestibular nucleus; lesions to
these midline areas result in deficits in posture,
locomotion and oculomotor control. The interme-
diate zone of the adjacent cerebellar hemisphere
mainly connects to the interpositus deep cerebellar
nucleus (globose and emboliform nuclei in
humans) and lesions here result in limb tremor
and impairments in limb motion
6
and dysarthria.
The lateral cerebellar hemisphere connects to the
dentate deep cerebellar nucleus; lesions here result
in poor visuomotor coordination.
7
More recently,
the finding of extensive connections between the
lateral hemisphere and prefrontal cortex in
humans and greater apes has highlighted a role
of the cerebellum in non-motor functions, such
as working memory as discussed later.
8,9
Blood supply
The cerebellum is supplied by three main arter-
ies that arise from the vertebrobasilar arteries. The
posterior inferior cerebellar artery supplies the
dorsal medulla (including parts of the vestibular
nuclei and the inferior cerebellar peduncle) and
the vermis and inferior cerebellum. The anterior
inferior cerebellar artery supplies the lateral pons
(including the facial nucleus and parts of the ves-
tibular nuclei and the middle cerebellar peduncle)
and the cerebellar flocculus and adjacent parts of
the inferior surface of the cerebellum. The anterior
inferior cerebellar artery also gives rise to the inter-
nal auditory and labyrinthine arteries. The supe-
rior cerebellar artery is the largest of the three
arteries; it supplies the upper pons (including supe-
rior cerebellar peduncle) and the superior part of
the cerebellum.
10
Cytoarchitecture
The cytoarchitecture of the cerebellar cortex is
very uniform throughout its extent.
11
The output
cells of the cerebellar cortex, the Purkinje cells,
mainly project to the deep cerebellar nuclei with
the exception of cells within the flocculus (see
above). Their dendrites are oriented in a parasagit-
tal direction. The cerebellar cortex receives two
main excitatory inputs: the climbing and mossy
fibres. Climbing fibres arise from defined areas of
inferior olive within the brainstem and project to a
small number of Purkinje cells in specific longitu-
dinal zones; one Purkinje cell receives one climbing
fibre. Mossy fibres convey inputs from all other
incoming pathways, such as the spinocerebellar
tracts and inputs from the cerebral cortex via the
pontine nuclei. These inputs synapse with the extre-
mely numerous granule cells (numbering between
10
10
and 10
11
) whose axons bifurcate giving rise to
parallel fibres. The parallel fibres run for about
27 mm in a medio-lateral direction, synapsing in
passing on Purkinje cells (up to 80 000 parallel
fibres synapse with 1 purkinje cell).
12
The uniformity of the cerebellar cytoarchitec-
ture suggests that the cerebellum may be perform-
ing an identical computational function in these
different areas. Many putative, not necessarily
mutually exclusive, functions of the cerebellum
have been put forward and include a role in:
motor learning and adaptation; coordination;
modulation of sensorimotor gain; timing; internal
representation of the dynamics of the limb and
sensorimotor transformations.
7,1319
At the heart
of many of these theories lies the interaction
between the climbing fibres and parallel fibres at
the level of the Purkinje cell.
Understanding the exact role of the cerebellum
in normal motor control will aid in our interpre-
tation and understanding of cerebellar ataxia and
ultimately help to guide treatment strategies.
Aetiology and prevalence
The aetiology of cerebellar ataxia is summarized in
Table 1. Of the hereditary ataxias the prevalence
of Friedreichs ataxia is estimated at 25 per
100 000, while the spinocerebellar ataxias have a
prevalence of between 0.9 and 3.0 per 100 000
depending on the exact type.
20,21
The most
common spinocerebellar ataxia is SCA6, which
mainly affects the cerebellum with minimal
additional extracerebellar pathology. Of the non-
hereditary ataxias, the most common cause of cer-
ebellar ataxia is multiple sclerosis (approximate
prevalence of 100 per 100 000
22
); here cerebellar
signs are felt to occur in between 10 and 50% of
cases, depending on the age of onset.
23,24
196 J Marsden and C Harris
Signs and symptoms
The classical motor signs and symptoms of cere-
bellar ataxia are summarized in Table 2.
Traditionally, an ipsilateral cerebellar hemi-
sphere lesion is felt to result in ipsilateral signs.
This is because the cerebellar hemispheres connect
with the contralateral cerebral cortex via the con-
tralateral ventrolateral nucleus of the thalamus
(also termed ventral intermediate nucleus in
humans
25
) and the cerebral cortex output; the cor-
ticospinal tract subsequently decussates.
26
Recent
findings, however, suggest that stimulation of the
interpositus nucleus in primates can result in bilat-
eral limb movements
27
and that a unilateral lesion
in humans can affect both limbs.
28
These bilateral
symptoms may be mediated via bilateral projec-
tions to subcortical sites such as the reticular for-
mation. These projections may be useful in
mediating bimanual coordination.
Pathophysiology
Limb movement
Dyssynergia and incoordination
People with cerebellar ataxia are slow to start
movements; they have an increased reaction time.
The movements themselves are prolonged in dura-
tion and they show a decreased maximal velocity
and an increase in spatial variability, that is, the
path that is followed varies from trial to trial.
2931
Variability in the spatial path is seen early in the
movement before there is any time to process
visual feedback, suggesting there is a problem
with movement planning. This also accounts for
the prolonged reaction time.
32
In keeping with an
important role of the cerebellum in planning
predictive movements fast, ballistic movements
that are entirely preplanned are inaccurate.
33
However, inaccuracies in slower movements may
also be seen as without predictive control these
movements now over-rely on time-delayed feed-
back signals.
People with cerebellar ataxia in particular show
marked deficits in multi-joint movements, called
dyssynergia. This, in part, results from an inability
tocompensate for movement-associatedinteraction
torques. Interaction torques are turning moments
brought on by movement about one joint that influ-
ence the motion of adjacent joints.
34,35
The deficits
in multi-joint movements mean that people with
cerebellar ataxia will tendtodecompose their move-
ments intosimpler, more accurate single joint move-
ments.
7,36
In addition to showing deficits in
coordination between the joints in one limb, abnor-
malities in intralimb coordination have also been
described
3739
(but see also ref. 40).
The cerebellum may coordinate the activity in
different effectors such as between the eye, arm,
leg or head.
4145
Deficits in ocular control and
limb control, for example during a reaching or
stepping task, co-vary suggesting that they may
be caused by common difficulties in programming
coordinated movements.
46,47
Such interactions
mean that the accuracy of eye and limb move-
ments performed in isolation may be further
degraded during coupled activities,
46,48,49
as usu-
ally occurs during functional activities.
Dysmetria and tremor
A triphasic pattern of muscle activation con-
sisting of alternating agonistantagonistagonist
activity is normally observed with fast single
joint movements. Both animal and human studies
highlight that following cerebellar dysfunction/
inactivation there may be a prolonged duration
Table 1 Aetiology of cerebellar ataxia
Hereditary Autosomal recessive:
Friedreichs ataxia
Ataxia telangiectasia
Abetalipoproteinaemia
Mitochondrial disorders
Autosomal dominant:
Spinocerebellar ataxia 1
Episodic ataxia (EA-1 and EA-2)
Acquired Tumours and paraneoplastic degeneration
Congenital malformations
Immune disease
Stroke
Trauma
Infections
Multisystem atrophy
Spongiform enchephalopathy
Corticobasal degeneration
Endocrine disorders
Acquired vitamin deficiency or metabolic
disorders
Toxins (e.g. alcohol, heavy metals,
antiepileptic medication)
Reproduced with kind permission from CRC Press.
288
Cerebellar ataxia: pathophysiology and rehabilitation 197
Table 2 Motor signs and symptoms and tests in cerebellar disease
Signs and symptoms of
cerebellar ataxia
Clinical tests Assess
Limb movement
Dyssynergia Finger to nose
Heel shin
Finger to finger test Great toefinger test (have
trunk supported to isolate any limb dysfunction)
Ability to move joints simultaneously/
decomposition of multijoint movements
Speed of motion
Variability of spatial path
Over/undershoot
Dysmetria
Tremor
Kinetic
Intention
Postural
Holding a position, e.g. (1) arms outstretched
with palms down; (2) index to index (hold
two index fingers medially)
Move to/from target (see tests above)
Assess writing/spiriography
Tremor amplitude and frequency
Assess for titubation 3 Hz tremor of
the head
Disdiadochokinesia Alternating pronationsupination
Alternating wrist flexion/extension while tapping
the thigh
Ankle dorsi-plantarflexion
Rate of movement
Asthenia and hypotonia Passive motion of the limb
Test muscle strength
Assess resistance to motion
Assess strength
Balance and gait dysfunction
Balance and gait
dysfunction
Stand with eyes open/closed
Stand in tandem/on one foot
Balance in response to perturbation, volitional
upper/lower limb
Walking
Rate, direction and amplitude of sway
( vision) and phase between upper and
lower body
Size of response to postural perturbation
Walking accuracy of foot placement/
degree of sway/time in double stance/
stride length/base of support
Oculomotor
Nystagmus (e.g. gaze-
evoked; downbeat;
rebound nystagmus)
Fixation deficits (e.g.
flutter; macroscopic
oscillations)
Ability to fixate into finger 30 cm away with
gaze in primary position and when looking at
eccentric targets and on returning gaze to
midline
Ocular alignment/presence of nystagmus
(rhythmic oscillatory movements of the
eyes) type/presence of eye movements
(e.g. flutter/ocular bobbing)
Saccadic smooth pursuit Follow a target moving up/down/side to side Number of catch-up saccades
Poor vestibulo-ocular
reflex cancellation
Hold arms together out in front with
thumbs pointing up. Fixate gaze on the
thumbs while sitting in a chair that is
moved side to side
Ability to maintain gaze fixation
Dysmetric saccades Ability to rapidly shift gaze from one eccentric
target to another (up and down/side to side)
Latency, velocity and precision (over/under-
shoot of the target as seen by the need
to make more than one saccade to reach
the target)
Reduced velocity of diver-
gent eye movement
Ability to shift gaze from targets close to and far
away from subject.
Ability to follow targets moving to and from
target
Latency, velocity and precision
Abnormal vestibulo-ocular
reflex and optokinetic
response
Sit on a chair and fixate an earth fixed target
while the chair rotates side to side
Look at an optokinetic drum (ask patient to
count the stripes)
Ability to fixate on the target
Movement of the eyes in the direction
of rotation and re-alignment to the
midline
Dysarthria
Ability to maintain sustained vowel phonation;
repeat syllables
Repeat a sentence speech/read a standard pas-
sage of text
Intelligibility; rhythm; speed; presence of
hesitations, accentuation of syllables and
addition/omission of pauses
Reproduced with kind permission from CRC Press.
288
of the initial agonist burst that accelerates the
limb and a delay in the onset of the subsequent
antagonist muscle burst.
5054
This antagonist
burst normally acts to decelerate the movement.
Its delay therefore results in the person over-
shooting the target,
55
a form of dysmetria.
Although delayed, activation of the anatagonist
muscle still occurs. However, instead of now
being pre-programmed by the cerebellum it is
felt to be activated through stretching via a pos-
sible transcortical stretch reflex. This antagonist
contraction can in turn stretch the agonist, result-
ing in stretch reflex-related activation of this
muscle. Thus, alternating agonistantagonist con-
tractions driven by proprioceptive feedback may
arise, resulting in a tremor.
52,5659
Cerebellar tremor is a type of action tremor. It is
seen while maintaining a posture (postural tremor)
and while moving (kinetic tremor). Tremor at rest
is not seen with pure cerebellar dysfunction.
Cerebellar tremor is complex and in addition to
proprioceptive feedback driving tremor other
causes exist. When approaching a target there is
a characteristic increase in tremor amplitude
(intention tremor).
60
Intention tremor may be
explained by the effects of the inherent delay in
visuomotor processing compounding the pres-
ence of an already incoordinated movement.
61,62
Visuomotor tracking tasks in people with cerebel-
lar ataxia have shown that the smoothness of
tracking is improved when vision of either the
target or the operator-controlled cursor is
removed.
6367
Both conditions prevent visual feed-
back about the error between the target and the
ongoing movement. It seems that people with cer-
ebellar ataxia use this visual feedback to try to
correct any abnormalities in tracking. However,
the inherent delay in the time it takes to process
visual feedback and to produce a motor output
(around 120 ms) results in a delayed response
during which time the limb may have moved in a
non-predictable direction due to the underlying
ataxia. In this case visually driven corrective
responses would only serve to compound the inac-
curacy in the movement, resulting in intention
tremor.
68
Although, avoiding visual feedback
during and towards the end of a movement may
improve the smoothness of the movement, this
strategy may decrease movement accuracy.
49,69,70
Force generation
Asthenia, a generalized weakness, was described
by Holmes (1922). This was more marked in the
acute stages and with extensive cerebellar lesions
and was not universally seen; indeed normal grip
force has been reported in cerebellar ataxia.
71
In contrast, a reduced rate of force generation
(power) has frequently been reported
6,7274
and
may in part underlie the difficulty in performing
rapidly alternating movements (disdiadochokin-
esis) and contribute to the inability to adequately
compensate for the higher interaction torques that
are generated with faster movements.
72,75,76
People with cerebellar ataxia also show more
variability in maintaining a constant level of
force.
77
The deficits in force generation may
affect precise manipulative tasks. This, along
with poor coupling between grip and load forces
and inappropriate finger placement on an object,
can lead to excessive self-generated torques acting
on the object.
6,7880
Balance and gait dysfunction
Postural sway and balance
People with lesions affecting the anterior lobe,
vermis and the interconnected fastigial nucleus
have an increase in postural sway with an associ-
ated head and truncal tremor between 2 and
5 Hz.
8186
The sway is greatest in the antero-
posterior direction. Instability in the medio-lateral
direction is also seen in response to alterations in
the available sensory input, following a postural
perturbation or while stepping.
8789
Impairments in both postural responses and
anticipatory postural adjustments have been
described.
90
The temporal coordination between
anticipatory postural adjustments and volitional
movements, for example, is impaired.
91
A lack of
such anticipatory adjustments will result in imbal-
ance during self-generated movements, for exam-
ple, not leaning forwards prior to standing on
tiptoes will result in the person pushing themselves
backwards.
In response to an unexpected perturbation
of the support surface, hypermetric postural
responses are observed.
87,9294
This seems to
reflect an inability to set the correct size (or gain)
of the response. Similar to healthy participants,
however, people with cerebellar ataxia are able to
decrease the size of the postural response with
repeated presentations of a predictable postural
perturbation and change their response magnitude
appropriately to an expected change in the size of
perturbation, although the overall size of the
response remains increased.
92,9598
Gait and falls
While walking, people with cerebellar dysfunc-
tion show prolonged time in double stance, poor
inter-limb coordination
99,100
and an increased var-
iability in their stride length and individual joint
kinematics,
101103
although their base of support
may not be increased as is often presumed.
104
Although primary deficits in balance can have a
direct and marked impact on walking,
105
dysme-
tria/dyssynergia affecting the lower limbs can also
impact on dynamic balance while walking.
99,106
When one foot is off the ground while walking,
the bodys centre of mass does not usually lie
over the base of support and so the body is in a
state of disequilibrium; it will tend to fall away
from the stance leg. The trajectory taken by the
body while walking is preprogrammed and tightly
coupled to the future placement of the stepping
foot that acts to catch the falling body.
107,108
Incorrect foot placement due to incoordination
of the lower limb, as is seen in cerebellar ataxia,
can therefore result in poor dynamic balance while
walking. A more medial foot placement than
required, for example, can result in the body fall-
ing laterally.
99
Deficits in balance and walking may contribute
to the high reported incidence of falls in cerebellar
ataxia.
82
However, the causes of falls are often
multifactorial and the relative contribution of
intrinsic and extrinsic (environmental) factors in
falls aetiology in cerebellar dysfunction remains
to be elucidated.
Oculomotor control
Normal oculomotor function is heavily dependent
on the cerebellum for adaptive control (plastic-
ity).
109,110
It helps to understand cerebellar oculomo-
tor dysfunction with reference to three major
cerebellar oculomotor areas: the flocculus/parafloc-
culus, the nodulus and the vermis, as each gives rise
to well-recognized (and recognizable) oculomotor
syndromes
111
that may or may not occur together
or be associated with other cerebellar signs.
111113
These syndromes can be useful diagnostic clues and
may account for visual symptoms (oscillopsia, dizzi-
ness, diplopia).
114
However, due to the heavy con-
nections with the brainstem, oculomotor centres in
the pontomedullary junction (horizontal eye move-
ments) and the midbrain (vertical and torsional eye
movements), it is often not possible to differentiate
between brainstem and cerebellar lesions.
The flocculus/paraflocculus controls the modu-
lation of retinal image motion (retinal slip) and
maintains steady fixation in eccentric gaze
directions (the neural integrator), accurate
smooth pursuit, optokinetic nystagmus and
normal vestibulo-ocular reflex gain. Visual input
from retina and visual cortex is relayed to the infe-
rior olive via pretectal nuclei, and uniquely,
Purkinje outputs synapse with brainstem centres
(bypassing the deep nuclei). Cardinal clinical
signs of the floccular syndrome are gaze-evoked
nystagmus on lateral gaze and jerky (saccadic)
smooth pursuit (ipsiversive to the lesion).
115121
Rebound nystagmus may also be present.
Vestibulo-ocular reflex suppression is impaired
which can be readily detected by the failure of a
(seeing) patient to suppress post-rotatory vestibu-
lar nystagmus.
122127
Vertical eye movements may be normal, but
in progressive disorders downbeat nystagmus
emerges.
128
Acute or chronic alcoholism may
yield similar signs and may be irreversible.
Downbeat nystagmus can give rise to constant
oscillopsia (the illusion of oscillation of the
visual surround) and poor visual acuity that is
unrelated to head movement and position.
113
Abnormalities in the direction and in the gain
(both increases and decreases) of the angular
and linear vestibulo-ocular reflex have been
reported.
125,129135
Abnormalities in the vesti-
bulo-ocular reflex can degrade visual acuity with
head motion. Vertical translational head motion is
especially prominent while walking, and abnor-
malities in the vertical vestibulo-ocular reflex
may lead to falls.
133
The nodulus (and ventral uvula)
Nystagmus is observed when people are rotated
in the dark at a constant angular velocity; the slow
phase being generated by the vestibulo-ocular
reflex with the fast phase serving to reposition
the eyes centrally in the orbit. The head velocity
signal derived from vestibular nerve afferents
is felt to be stored within brainstem circuits.
Evidence for this storage mechanism comes from
the observation that with a constant velocity rota-
tion in the dark, the velocity of the slow phase
decays exponentially with a time constant of
1520 seconds, slower than the decay in vestib-
ular nerve afferent signals.
136
The nodulus modulates this vestibular time-
constant, and lesions thereof tend to increase the
vestibular time-constant beyond normal, and can
lead to periodic alternating nystagmus, in which
the horizontal jerk nystagmus spontaneously
reverses direction with a period of tens of sec-
onds.
111
Periodic alternating nystagmus is often
missed due to the need to observe nystagmus for
some minutes. Midline cerebellar lesions can also
alter the time constant of perceptual vestibular-
mediated self-motion.
137
The dorsal vermis and fastigial nucleus
The dorsal vermis (lobules 6 and7) andthe fastigial
nucleus are important for the calibration of saccades.
The vermis syndrome is characterized by saccade
hypo- or hypermetria.
122,138,139
Detection of dysme-
tria requires careful observation, but extreme hyper-
metria may give rise to saccadic oscillations (distinct
fromnystagmus) and is suggestive of a nuclear lesion.
Smooth pursuit and slow vergence movements may
also be affected; in particular the velocity of diver-
gence is reduced.
140
In children, congenital or
acquired vermian lesions also lead to difficulties in
triggering saccades (saccade initiation failure or
congenital ocular motor apraxia) which is often
associated with speech apraxia due presumably to
co-involvement of vermian speech areas (see section
on Dysarthria, communication and language).
Saccade speed appears not to be controlled by
the cerebellum, and saccades that are clinically rec-
ognizable as being slow are usually caused by
brainstem disease or drug toxicities.
Vertigo may be experienced secondary to lesions
affecting the midline vermis and flocculonodular
lobe.
141,142
Prolonged isolated vertigo with imbal-
ance that mimics symptoms of vestibular neuritis
may be observed in 10% of cases of discrete cer-
ebellar lesions. These most commonly affect the
medial branch of the posterior inferior cerebellar
artery territory.
143
Vertigo may also be positional
and accompanied by positional evoked nystag-
mus,
142,144,145
thus mimicking benign paroxysmal
positional vertigo. In contrast to benign paroxys-
mal positional vertigo, the nystagmus may be either
vertical (up or downbeat) or torsional in direction
with the eyes straight ahead, be persistent and
change in direction with different head positions.
146
Additional signs that may alert the clinician to the
presence of a central cause of vertigo include the
presence of skew deviation, gaze evoked nystagmus
towards the affected ear (in the opposite direction
to that seen with peripheral vestibular neuritis),
vertical saccadic pursuit; a normal head thrust
test and minimal increase in the slow phase velocity
of sponataneous nystagmus in the dark compared
to fixation in the light as well as the presence of
associated neurological signs such as dysmetria/
dysynergia or dysarthria.
147,148
Dysarthria, communication and language
Dysarthria is commonly observed with lesions
affecting the rostral paravermal region of the ante-
rior lobes.
3,149151
Impairments in both articu-
lation and prosody have been described.
152
Commonly speech is described as scanning in
nature consisting of hesitations, accentuation of
some syllables and the addition of pauses or omis-
sion of appropriate pauses; in around 50% of
cases slurring may be evident.
153
In addition,
speech can be reduced in rate, and show signs of
vocal instability, increased monotony, equalized
stress and imprecise consonants.
154
Acoustic anal-
ysis reveals more variable/longer syllable produc-
tion and pause durations, reductions in vowel
length contrasts and differences in the frequency
spectrum from those in healthy controls.
154156
Speech intelligibility may be affected by difficulties
in distinguishing the difference between plosives
(e.g. [p], [t], [k]) at the end of words.
157
Kinematic analysis of oro-facial movements
highlights similar changes as previously described
for limb movements, such as prolongation of
movement duration; decreased maximal velocity
and prolonged muscle bursts.
158160
Furthermore,
a 3 Hz postural tremor may be detected during
sustained phonation of vowels
161
and oral disdia-
dochokinesia can be detected during rapid syllable
repetition,
162
although this may not predict the
syllabic rate during sentence production.
163
Language impairments that are not attributed
to dysarthria, such as poor understanding of
speech, reading and naming tasks, and agramma-
tism have been reported following cerebellar
damage
164,165
(although see ref. 166). These are
felt to arise from disruption to reciprocal path-
ways between the right cerebellar hemisphere and
left cerebral hemisphere and highlight the role of
the cerebellum in pre-articulatory speech.
167,168
Mutism following posterior fossa tumour resec-
tion in children has also been described in about
29% of cases.
151,169,170
The mutism may not
develop immediately and is usually self-limiting.
170
Here damage to the vermis has been impli-
cated,
151,169
although cerebellar damage leading
to a temporary reduction in activity in the inter-
connected cerebral cortex has also been
suggested.
151,171,172
Non-motor symptoms
In the last two decades accumulating evidence
suggests that isolated damage to the cerebellum
may also result in a cerebellar cognitive affective
syndrome.
173
This syndrome includes non-motor
symptoms such as poor executive function (e.g.
reduced verbal fluency and working memory);
impaired spatial cognition (eg poor visuo-spatial
memory) and linguistic difficulties (e.g. dysproso-
dia and agrammatism) and has been described in
both acquired and hereditary cerebellar dysfunc-
tion.
174180
The symptoms are more marked in the
acute/subacute stages of damage/dysfunction, par-
ticularly when the posterior lobes of the cerebel-
lum are affected bilaterally (e.g. following an
infarction within the posterior inferior cerebellar
artery territory). Further, affective symptoms
such as apathy and disinhibited behaviour may
occur with damage to the midline vermis.
181,182
These symptoms are felt to reflect damage to the
extensive reciprocal pathways between the cerebel-
lum and the posterior parietal, superior temporal,
prefrontal and parahippocampal cortices. Thus,
the role of the cerebellum in planning and ongoing
control of motor function may therefore have a
corollary in non-motor behaviours.
181
Such non-motor symptoms may further impact
on rehabilitation, for example, by affecting the
ability to retain information conveyed through
verbal or visual instructions; to perform abstract
reasoning or to initiate activities.
183,184
Implications for rehabilitation
approaches
As highlighted in recent systematic reviews of ran-
domized controlled trials there is currently a lack
of high-quality research studies into the rehabili-
tation of cerebellar ataxia.
185,186
Despite this, the
literature on the treatment of cerebellar ataxia
describes some approaches that warrant further
investigation. Approaches may be broadly divided
into those that aim to improve functional ability
by compensating for the underlying deficit and
those that aim to improve function through restor-
ative techniques that involve adaptation and
recovery within the neuro-musculoskeletal system.
Compensatory approaches
Compensatory approaches include the use of
strategies to encourage decomposition of move-
ment into simpler single joint movements
187
;
visual and verbal cues to aid walking speed and
stride length
188,189
; the use of assistive technology
to aid computer use
190
; and aids such as custom-
ized seating and frames to help posture, balance
and mobility.
191193
Increasing the visco-elastic resistance or the
inertia of a limb will dampen the tremor and
serve to decrease the speed and size of the stretch
reflex that may drive the tremor in some
cases.
63,194
Thus aids that increase viscous resis-
tance such as the Neater Eater and Mouse Trap
(http://www.neater.co.uk/main.htm) have been
recommended although their effectiveness has
not been thoroughly investigated. The visco-elastic
resistance offered by Lycra garments
195
may also
underlie their proposed use in improving proxi-
mal and truncal stability and function in people
with cerebellar signs. However, any functional
improvements with Lycra garments in reported
single-case studies to date need to be considered
alongside the possible inconvenience and addi-
tional assistance required in applying the garment,
leading to a potential loss in independence.
196
Increasing inertia by loading the appendicular
or axial skeleton may also dampen tremor and
reduce dysmetria.
63,197,198
Studies into the effec-
tiveness of weights in improving upper limb func-
tion are variable, with improvements and
deterioration in function as well as a lack of
effect being reported.
49,199201
This may be because
the addition of a load requires adaptive scaling of
agonistantagonist activity which is affected in
cerebellar disease. Thus, although an increase in
agonist activity required to initially accelerate the
limb may be seen, this may not be accompanied by
an increase in antagonist braking activity.
Ultimately, this results in an increase in overshoot-
ing and potential deterioration in function.
201
In
fact the use of additional load may be beneficial as
an assessment aid in revealing minimal hyperme-
tria.
202
Loading the trunk may aid balance, and
here the loading may be either symmetrical or
asymmetrical to counterbalance a directional
impairment in balance (e.g. anterior loading is
provided to counterbalance falling backwards).
Although it is not always clear whether the
ataxia is of pure cerebellar origin, case reports of
these interventions show a favourable outcome on
clinical measures of walking and balance.
197,203,204
Cooling a limb can also temporarily reduce
cerebellar tremor. This may occur through a
reduction in muscle thixotropy and increase in
muscle stiffness as well as a reduction in nerve
conduction velocity and muscle spindle afferent
feedback.
205,206
Cooling-related reductions in
tremor resulting in functional improvements have
also been reported in people with essential
tremor.
207,208
Restorative approaches
The uses of defined restorative approaches tar-
geting a specific symptom are rare and involve
uncontrolled case reports. With prolonged inter-
ventions (312 months) improvements in inter-
limb coordination
209,210
and a reduction in force
variability have been described.
191
Biofeedback of
different aspects of motor control has been
assessed. Biofeedback of EMG patterns during a
visuomotor tracking task led to an improvement
in muscle activation on the trained task after sev-
eral weeks of training although the effects on func-
tional tasks were not investigated.
211
Biofeedback
of muscle activity has also been described in com-
bination with relaxation therapy to decrease
tremor resulting in improved feeding.
212,213
Biofeedback of the centre of pressure motion (a
measure of postural sway) linked to a computer
game resulted in improvement in measures of bal-
ance and falls and the use of a computer game was
linked to increased practice time.
214
Other studies have assessed the effect of multi-
component approaches on balance and walking.
Some of these are the subject of recent systematic
reviews.
185,186
Balance and ocular exercises have
led to an improvement in clinical measures of pos-
tural stability and walking in people with cerebel-
lar ataxia.
215
Although this study involved small
numbers (n 2), the techniques utilized are based
on those that are effective in treating deficits
affecting the peripheral and central vestibular
system with which the cerebellum has large recip-
rocal connections. Brown et al.
216
also used vestib-
ular habituation training in combination with
strengthening, stretching and gait re-education.
Significant improvements in disability scales
(Disability Handicap Inventory; Dynamic Gait
Index) were seen in the subgroup of people with
cerebellar ataxia (n 10). Increases in walking dis-
tance following either locomotor training using
body weight support on a treadmill (5 days/week
for four months) or by encouraging people to
decrease the amount of fixation of the arms
when walking
217,218
have been reported.
Improvements in standing balance have also
been seen with a combination of strength and
balance exercises.
219,220
Both groups utilized
Frenkels exercises that were originally developed
for people with sensory ataxia secondary to tabes
dorsalis (Frenkel, 1902). These exercises emphasize
a reliance on visual feedback to control movement.
Given that visual feedback can improve balance/
postural sway in cerebellar dysfunction,
81,221
this may be a useful approach although an over-
reliance on vision in cerebellar dysfunction result-
ing in visual vertigo has been described.
222
It would
be interesting to contrast the reliance of different
sensations on balance following this approach with
that seen after the vestibular habituation/rehabili-
tation exercises described above.
Several small-scale studies on training ocular
control and dysarthria highlight the potential
value of further intervention studies in these
areas. In a stepping task that defined the target
for foot placement, Crowdy et al. found that sac-
cadic and foot placement accuracy could be
improved by prior practice in making saccadic
eye movements towards the targets.
223
A single-
case study of a person with cerebellar dysfunction
secondary to thiamine deficiency assessed the
effects of Lee Silverman voice treatment. This
approach emphasizes loudness of phonation and
is more commonly used in the treatment of people
with Parkinsons disease. After a four-week inter-
vention period (16 sessions), improvements in
acoustic measures (sound pressure level) and per-
ceptual measures of articulation/phonation were
observed and their employer reported increased
satisfaction over the effectiveness of communica-
tion via the telephone.
224
More recently, the use of motor cortical stimu-
lation as a treatment paradigm has been assessed.
These follow animal and human studies showing
that cerebellar dysfunction results in a reduction in
measures of motor cortex excitability.
225234
Koch
et al. investigated the effect of rapid transcranial
magnetic stimulation (5 Hz) over the motor cortex.
The frequency and paradigm of stimulation used
had previously been shown to result in an increase
in motor cortex excitability and was associated in
the cerebellar ataxic group with an improvement
in hand function (as determined by the 9-hole peg
test) compared to healthy controls.
235
Direct stimulation of the cerebellum has
also been investigated. Stimulation of the cerebel-
lum using transcranial magnetic stimulation in
healthy participants has also been shown to mod-
ulate cortical excitability.
236244
In people with
spinocerebellar degeneration, cerebellar stimula-
tion was applied over several sessions with treat-
ment lasting from 21 days to eight weeks.
Improvements in clinical measures of ataxia, bal-
ance and gait were reported although there were
no control groups.
245,246
The mechanisms under-
lying any functional improvements with stimula-
tion of the cerebellum remains unclear given the
fact that transcranial magnetic stimulation over
the cerebellum may in part affect motor cortex
excitability by stimulating adjacent peripheral
nerves.
247,248
Understanding when to apply restorative or
compensatory strategies remains unclear. The rel-
ative use of compensatory strategies may vary and
possibly depends on disease progression and
severity.
Potential mechanisms and barriers
to recovery
The potential mechanisms of recovery following
cerebellar damage have not been extensively stud-
ied. The results of serial experimental cerebellar
lesions in primates suggest that following unilat-
eral cerebellar lesions, important structures
mediating recovery are the opposite cerebellar
hemisphere, deep cerebellar nuclei, as well as
extracerebellar sites within the brainstem and sen-
sorimotor cortex, the latter depending on whether
volitional limb movements or walking/balance is
being investigated.
249253
Extrapolation of such
findings to humans should be made with caution
due to differences in neuroanatomy.
254,255
A cerebellar lesion may also cause loss of activ-
ity within the cerebral cortex due to the large inter-
connections between these structures. Resolution
of such disachisis may also underlie symptom
recovery.
256,257
In humans with cerebellar dysfunc-
tion, for example, an increase in the activation of
the medial premotor system (supplementary motor
area) while moving has been reported; this may
compensate for the lack of activation of the lateral
premotor areas that receive extensive inputs from
the cerebellum.
258
Furthermore, following a uni-
lateral lesion, imbalances in activity between left
and right cerebellum and their interconnected cor-
tical structures may also contribute to symptom
presentation. Torriero et al. hypothesized that
isolated damage to the left cerebellum may
reduce excitatory drive to the contralateral right
dorsolateral prefrontal cortex, resulting in an
imbalance in activity between the left and right
cortex. Re-addressing this imbalance temporarily
by inactivating the left dorsolateral prefrontal
cortex using rapid transcranial magnetic stimula-
tion resulted in an improvement in a procedural
learning task.
259
Such findings are in keeping with
evidence from subcortical stroke, where changes in
interhemispheric inhibition from the unaffected to
the affected side may contribute to paresis.
260
The cause, site and extent of the lesion are
important predictors of the degree of functional
recovery. Functional deficits seem more marked
following a haemorrhage compared to an infarct,
and superior cerebellar artery strokes have a worse
prognosis than strokes affecting the posterior and
anterior inferior cerebellar arteries
261,262
(although
see ref. 263). Superior cerebellar artery strokes
may be associated with damage to the dentate
nucleus and the superior cerebellar peduncle, the
main output pathway of the cerebellum. This is in
keeping with other studies highlighting worse
functional recovery with lesions affecting the
output pathways of the deep cerebellar nuclei
and superior cerebellar peduncle.
70,264
Extracerebellar damage seems to be a poor
prognostic indicator of functional recovery.
265
Functional recovery after a cerebellar stroke, for
example, is worse when people initially present
with global signs such as loss of consciousness/
weakness, as opposed to isolated focal signs such
as ataxia or vertigo.
261,266,267
Following stroke,
increasing age is also associated with worse func-
tional outcome,
267
although this may in part be
explained by the association of age-related addi-
tional extracerebellar white matter lesions.
268
Against an effect of age on prognosis is the finding
that the ability to compensate for a cerebellar
tumour post resection does not seem to be better
in young children (54 years old) than in older chil-
dren, adolescents and adults.
264,269
In other pathologies the presence of additional
cerebellar dysfunction strongly impacts on recov-
ery. The recovery from a peripheral vestibular
nerve lesion and the recovery from a brainstem
stroke is less pronounced in the presence of an
additional cerebellar lesion.
270,271
This may
simply reflect an increasing accumulation of
pathology. However, it may also reflect that the
cerebellum normally plays an important role in
motor learning and the recovery of symptoms
following damage to other central and peripheral
nervous system structures.
Motor learning, adaptation and recovery
The role of the cerebellum in motor learning is
being investigated at a subcellular, cellular and sys-
tems level in both animals and humans and using
neural networks and modelling.
18
The cerebellumis
part of a distributed system that is involved in
motor learning and is felt to play a pivotal role in
error-based motor learning and adaptation.
272,273
In keeping with this, people with cerebellar ataxia
may show greatly impaired learning of both simple
and complex motor skills such as visuomotor adap-
tation,
274276
serial reaction time tasks,
277,278
adap-
tation to prism glasses
279
and force fields,
280
as well
as classical conditioning paradigms when the inter-
val between the unconditioned and conditioned
stimulus is short (400 ms).
281285
Importantly,
such adaptation is constantly occurring in everyday
life. Tasks such as adapting the arm to its new
length and dynamics when holding an object
(e.g. a pen), adapting the vestibulo-ocular reflex
when glasses are put on and adapting to the effects
of muscle fatigue
286
with repetitive activities all
seem to require cerebellar activity.
Poor recovery following a cerebellar lesion may
be a consequence of damaging structures critically
involved in learning and relearning of motor skills.
However, following a cerebellar lesion learning
and adaptation over time has been described,
albeit at a lower rate and extent than that in
healthy controls.
73,98,287
It remains to be seen
whether this reflects activity within undamaged
areas of the cerebellum or activity in extracerebel-
lar structures.
Conclusion
An understanding of the pathophysiology of cere-
bellar ataxia and the mechanisms of recovery can
help to guide the development of treatments and
to optimize current interventions. Interpreting
studies of pathophysiology in turn crucially
depends on our understanding of the healthy cer-
ebellum in both motor and non-motor functions.
Although there is currently a lack of high-quality
research studies into the rehabilitation of cerebel-
lar ataxia, current studies highlight some potential
avenues that warrant further investigation. Future
studies should aim to identify the site and extent of
both cerebellar and extracerebellar pathology as
these may crucially determine clinical presentation
and prognosis. A detailed description of the per-
sons presenting impairment profile should be cou-
pled with appropriate outcome measures of the
effects of intervention on a persons ability and
participation.
Clinical messages
The key role of the cerebellum in motor
learning and in adaptation following extra-
cerebellar pathology may limit functional
recovery in people with cerebellar dysfunc-
tion.
Associated cognitive and affective signs may
further impact on function and the rehabili-
tation process.
There is limited evidence about the effective-
ness of interventions in people with cerebellar
dysfunction although clinical improvements
in balance, walking and upper limb function
have been reported. A combination of
restorative and compensatory techniques
may be utilized; the relative emphasis
depending on the severity of cerebellar
ataxia and its pattern of progression.
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