Cerebellar Ataxia

Clinical Rehabilitation 2011; 25: 195–216

Rehabilitation in practice

Cerebellar ataxia: pathophysiology and rehabilitationJon Marsden School of Health Professions, Faculty of Health, University of Plymouth andChris 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 significantfunctional difficulties with upper and lower limbmovement, oculo-motor control, balance andwalking. Such difficulties can affect employability,increase carer burden and reduce a person’s per-ceived quality of life.1 The economic burden ofpeople with spinocerebellar ataxia is estimated tobe around E18 776 per annum.1 This articlewill review the signs and symptoms and patho-physiology of cerebellar ataxia, highlighting thetheoretical basis of current non-surgical and non-pharmacological rehabilitation techniques.

Search strategy and selection criteria

References for this review were identified from asearch 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 rehabilitationor therapy’). Articles were further identified throughsearches of reference lists in identified papers.

Anatomy

Gross anatomyCerebellar ataxia arises due damage or dysfunc-

tion affecting the cerebellum and/or its input/output pathways. In a rostro-caudal direction thecerebellum can be divided into three lobes: ante-rior, posterior and flocculo-nodular. Some of thesemay take the brunt of certain pathologies. Theanterior lobe, for example, is particularly affectedin alcoholic cerebellar degeneration.2 The cerebel-lum connects to the medulla, pons and midbrainvia the inferior (restiform body), middle and supe-rior cerebellar peduncles through which pass affer-ent and efferent pathways.

Functionally, the cerebellum is organized ina medio-lateral fashion with different areas ofthe cerebellum having a distinct anatomical

Address for correspondence: Professor Jon Marsden, School ofHealth Professions, Peninsula Allied Health Centre, DerrifordRoad, University of Plymouth PL6 8BH, UK.e-mail: [email protected]

� The Author(s), 2011.Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav 10.1177/0269215510382495

input–output relationship resulting in a specificlesion–symptom relationship.3–5 The midlinevermis connects to the fastigial deep cerebellarnucleus, while the flocculonodular lobe is con-nected with the vestibular nucleus; lesions tothese midline areas result in deficits in posture,locomotion and oculomotor control. The interme-diate zone of the adjacent cerebellar hemispheremainly connects to the interpositus deep cerebellarnucleus (globose and emboliform nuclei inhumans) and lesions here result in limb tremorand impairments in limb motion6 and dysarthria.The lateral cerebellar hemisphere connects to thedentate deep cerebellar nucleus; lesions here resultin poor visuomotor coordination.7 More recently,the finding of extensive connections between thelateral hemisphere and prefrontal cortex inhumans and greater apes has highlighted a roleof the cerebellum in non-motor functions, suchas working memory as discussed later.8,9

Blood supplyThe cerebellum is supplied by three main arter-

ies that arise from the vertebrobasilar arteries. Theposterior inferior cerebellar artery supplies thedorsal medulla (including parts of the vestibularnuclei and the inferior cerebellar peduncle) andthe vermis and inferior cerebellum. The anteriorinferior 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 ofthe inferior surface of the cerebellum. The anteriorinferior cerebellar artery also gives rise to the inter-nal auditory and labyrinthine arteries. The supe-rior cerebellar artery is the largest of the threearteries; it supplies the upper pons (including supe-rior cerebellar peduncle) and the superior part ofthe cerebellum.10

CytoarchitectureThe cytoarchitecture of the cerebellar cortex is

very uniform throughout its extent.11 The outputcells of the cerebellar cortex, the Purkinje cells,mainly project to the deep cerebellar nuclei withthe exception of cells within the flocculus (seeabove). Their dendrites are oriented in a parasagit-tal direction. The cerebellar cortex receives two

main excitatory inputs: the climbing and mossyfibres. Climbing fibres arise from defined areas ofinferior olive within the brainstem and project to asmall number of Purkinje cells in specific longitu-dinal zones; one Purkinje cell receives one climbingfibre. Mossy fibres convey inputs from all otherincoming pathways, such as the spinocerebellartracts and inputs from the cerebral cortex via thepontine nuclei. These inputs synapse with the extre-mely numerous granule cells (numbering between1010 and 1011) whose axons bifurcate giving rise toparallel fibres. The parallel fibres run for about2–7mm in a medio-lateral direction, synapsing inpassing on Purkinje cells (up to 80 000 parallelfibres 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 thesedifferent areas. Many putative, not necessarilymutually exclusive, functions of the cerebellumhave been put forward and include a role in:motor learning and adaptation; coordination;modulation of sensorimotor gain; timing; internalrepresentation of the dynamics of the limb andsensorimotor transformations.7,13–19 At the heartof many of these theories lies the interactionbetween the climbing fibres and parallel fibres atthe level of the Purkinje cell.

Understanding the exact role of the cerebellumin normal motor control will aid in our interpre-tation and understanding of cerebellar ataxia andultimately help to guide treatment strategies.

Aetiology and prevalence

The aetiology of cerebellar ataxia is summarized inTable 1. Of the hereditary ataxias the prevalenceof Friedreich’s ataxia is estimated at 2–5 per100 000, while the spinocerebellar ataxias have aprevalence of between 0.9 and 3.0 per 100 000depending on the exact type.20,21 The mostcommon spinocerebellar ataxia is SCA6, whichmainly affects the cerebellum with minimaladditional extracerebellar pathology. Of the non-hereditary ataxias, the most common cause of cer-ebellar ataxia is multiple sclerosis (approximateprevalence of 100 per 100 00022); here cerebellarsigns are felt to occur in between 10 and 50% ofcases, 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 connectwith the contralateral cerebral cortex via the con-tralateral ventrolateral nucleus of the thalamus(also termed ventral intermediate nucleus inhumans25) and the cerebral cortex output; the cor-ticospinal tract subsequently decussates.26 Recentfindings, however, suggest that stimulation of theinterpositus nucleus in primates can result in bilat-eral limb movements27 and that a unilateral lesionin humans can affect both limbs.28 These bilateralsymptoms may be mediated via bilateral projec-tions to subcortical sites such as the reticular for-mation. These projections may be useful inmediating bimanual coordination.

Pathophysiology

Limb movementDyssynergia and incoordination

People with cerebellar ataxia are slow to startmovements; they have an increased reaction time.

The movements themselves are prolonged in dura-tion and they show a decreased maximal velocityand an increase in spatial variability, that is, thepath that is followed varies from trial to trial.29–31

Variability in the spatial path is seen early in themovement before there is any time to processvisual feedback, suggesting there is a problemwith movement planning. This also accounts forthe prolonged reaction time.32 In keeping with animportant role of the cerebellum in planningpredictive movements fast, ballistic movementsthat are entirely preplanned are inaccurate.33

However, inaccuracies in slower movements mayalso be seen as without predictive control thesemovements now over-rely on time-delayed feed-back signals.

People with cerebellar ataxia in particular showmarked deficits in multi-joint movements, calleddyssynergia. This, in part, results from an inabilityto compensate formovement-associated interactiontorques. Interaction torques are turning momentsbrought on bymovement about one joint that influ-ence the motion of adjacent joints.34,35 The deficitsin multi-joint movements mean that people withcerebellar ataxiawill tend to decompose theirmove-ments into simpler,more accurate single jointmove-ments.7,36 In addition to showing deficits incoordination between the joints in one limb, abnor-malities in intralimb coordination have also beendescribed37–39 (but see also ref. 40).

The cerebellum may coordinate the activity indifferent effectors such as between the eye, arm,leg or head.41–45 Deficits in ocular control andlimb control, for example during a reaching orstepping task, co-vary suggesting that they maybe caused by common difficulties in programmingcoordinated movements.46,47 Such interactionsmean that the accuracy of eye and limb move-ments performed in isolation may be furtherdegraded during coupled activities,46,48,49 as usu-ally occurs during functional activities.

Dysmetria and tremorA triphasic pattern of muscle activation con-

sisting of alternating agonist–antagonist–agonistactivity is normally observed with fast singlejoint movements. Both animal and human studieshighlight that following cerebellar dysfunction/inactivation there may be a prolonged duration

Table 1 Aetiology of cerebellar ataxia

Hereditary Autosomal recessive:Friedreich’s ataxiaAtaxia telangiectasiaAbetalipoproteinaemiaMitochondrial disorders

Autosomal dominant:Spinocerebellar ataxia 1Episodic ataxia (EA-1 and EA-2)

Acquired Tumours and paraneoplastic degenerationCongenital malformationsImmune diseaseStrokeTraumaInfectionsMultisystem atrophySpongiform enchephalopathyCorticobasal degenerationEndocrine disordersAcquired vitamin deficiency or metabolic

disordersToxins (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 ofcerebellar ataxia

Clinical tests Assess

Limb movementDyssynergia Finger to nose

Heel shinFinger to finger test Great toe–finger test (havetrunk supported to isolate any limb dysfunction)

Ability to move joints simultaneously/decomposition of multijoint movementsSpeed of motionVariability of spatial pathOver/undershoot

Dysmetria

TremorKineticIntentionPostural

Holding a position, e.g. (1) arms outstretchedwith palms down; (2) index to index (holdtwo index fingers medially)Move to/from target (see tests above)Assess writing/spiriography

Tremor amplitude and frequencyAssess for titubation �3 Hz tremor ofthe head

Disdiadochokinesia Alternating pronation–supinationAlternating wrist flexion/extension while tappingthe thighAnkle dorsi-plantarflexion

Rate of movement

Asthenia and hypotonia Passive motion of the limbTest muscle strength

Assess resistance to motionAssess strength

Balance and gait dysfunctionBalance and gait

dysfunctionStand with eyes open/closed

Stand in tandem/on one footBalance in response to perturbation, volitionalupper/lower limbWalking

Rate, direction and amplitude of sway(� vision) and phase between upper andlower bodySize of response to postural perturbationWalking – accuracy of foot placement/degree of sway/time in double stance/stride length/base of support

OculomotorNystagmus (e.g. gaze-

evoked; downbeat;rebound nystagmus)Fixation deficits (e.g.flutter; macroscopicoscillations)

Ability to fixate into finger �30 cm away withgaze in primary position and when looking ateccentric targets and on returning gaze tomidline

Ocular alignment/presence of nystagmus(rhythmic oscillatory movements of theeyes) 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 saccadesPoor vestibulo-ocular

reflex cancellationHold arms together out in front with

thumbs pointing up. Fixate gaze on thethumbs while sitting in a chair that ismoved side to side

Ability to maintain gaze fixation

Dysmetric saccades Ability to rapidly shift gaze from one eccentrictarget to another (up and down/side to side)

Latency, velocity and precision (over/under-shoot of the target as seen by the needto make more than one saccade to reachthe target)

Reduced velocity of diver-gent eye movement

Ability to shift gaze from targets close to and faraway from subject.Ability to follow targets moving to and fromtarget

Latency, velocity and precision

Abnormal vestibulo-ocularreflex and optokineticresponse

Sit on a chair and fixate an earth fixed targetwhile the chair rotates side to sideLook at an optokinetic drum (ask patient tocount the stripes)

Ability to fixate on the targetMovement of the eyes in the directionof rotation and re-alignment to themidline

DysarthriaAbility to maintain sustained vowel phonation;

repeat syllablesRepeat a sentence speech/read a standard pas-sage of text

Intelligibility; rhythm; speed; presence ofhesitations, accentuation of syllables andaddition/omission of pauses

Reproduced with kind permission from CRC Press.288


of the initial agonist burst that accelerates thelimb and a delay in the onset of the subsequentantagonist muscle burst.50–54 This antagonistburst 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 anatagonistmuscle still occurs. However, instead of nowbeing pre-programmed by the cerebellum it isfelt to be activated through stretching via a pos-sible transcortical stretch reflex. This antagonistcontraction can in turn stretch the agonist, result-ing in stretch reflex-related activation of thismuscle. Thus, alternating agonist–antagonist con-tractions driven by proprioceptive feedback mayarise, resulting in a tremor.52,56–59

Cerebellar tremor is a type of action tremor. It isseen while maintaining a posture (postural tremor)and while moving (kinetic tremor). Tremor at restis not seen with pure cerebellar dysfunction.Cerebellar tremor is complex and in addition toproprioceptive feedback driving tremor othercauses exist. When approaching a target there isa characteristic increase in tremor amplitude(intention tremor).60 Intention tremor may beexplained by the effects of the inherent delay invisuomotor 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 oftracking is improved when vision of either thetarget or the operator-controlled cursor isremoved.63–67 Both conditions prevent visual feed-back about the error between the target and theongoing movement. It seems that people with cer-ebellar ataxia use this visual feedback to try tocorrect any abnormalities in tracking. However,the inherent delay in the time it takes to processvisual feedback and to produce a motor output(around 120ms) results in a delayed responseduring which time the limb may have moved in anon-predictable direction due to the underlyingataxia. In this case visually driven correctiveresponses would only serve to compound the inac-curacy in the movement, resulting in intentiontremor.68 Although, avoiding visual feedbackduring and towards the end of a movement mayimprove the smoothness of the movement, thisstrategy may decrease movement accuracy.49,69,70

Force generationAsthenia, a generalized weakness, was described

by Holmes (1922). This was more marked in theacute stages and with extensive cerebellar lesionsand was not universally seen; indeed normal gripforce has been reported in cerebellar ataxia.71

In contrast, a reduced rate of force generation(power) has frequently been reported6,72–74 andmay in part underlie the difficulty in performingrapidly alternating movements (disdiadochokin-esis) and contribute to the inability to adequatelycompensate for the higher interaction torques thatare generated with faster movements.72,75,76

People with cerebellar ataxia also show morevariability in maintaining a constant level offorce.77 The deficits in force generation mayaffect precise manipulative tasks. This, alongwith poor coupling between grip and load forcesand inappropriate finger placement on an object,can lead to excessive self-generated torques actingon the object.6,78–80

Balance and gait dysfunctionPostural sway and balance

People with lesions affecting the anterior lobe,vermis and the interconnected fastigial nucleushave an increase in postural sway with an associ-ated head and truncal tremor between 2 and5Hz.81–86 The sway is greatest in the antero-posterior direction. Instability in the medio-lateraldirection is also seen in response to alterations inthe available sensory input, following a posturalperturbation or while stepping.87–89

Impairments in both postural responses andanticipatory postural adjustments have beendescribed.90 The temporal coordination betweenanticipatory postural adjustments and volitionalmovements, for example, is impaired.91 A lack ofsuch anticipatory adjustments will result in imbal-ance during self-generated movements, for exam-ple, not leaning forwards prior to standing ontiptoes will result in the person pushing themselvesbackwards.

In response to an unexpected perturbationof the support surface, hypermetric posturalresponses are observed.87,92–94 This seems toreflect an inability to set the correct size (or gain)of the response. Similar to healthy participants,


however, people with cerebellar ataxia are able todecrease the size of the postural response withrepeated presentations of a predictable posturalperturbation and change their response magnitudeappropriately to an expected change in the size ofperturbation, although the overall size of theresponse remains increased.92,95–98

Gait and fallsWhile walking, people with cerebellar dysfunc-

tion show prolonged time in double stance, poorinter-limb coordination99,100 and an increased var-iability in their stride length and individual jointkinematics,101–103 although their base of supportmay not be increased as is often presumed.104

Although primary deficits in balance can have adirect and marked impact on walking,105 dysme-tria/dyssynergia affecting the lower limbs can alsoimpact on dynamic balance while walking.99,106

When one foot is off the ground while walking,the body’s centre of mass does not usually lieover the base of support and so the body is in astate of disequilibrium; it will tend to fall awayfrom the stance leg. The trajectory taken by thebody while walking is preprogrammed and tightlycoupled to the future placement of the steppingfoot that acts to catch the ‘falling’ body.107,108

Incorrect foot placement due to incoordinationof the lower limb, as is seen in cerebellar ataxia,can therefore result in poor dynamic balance whilewalking. A more medial foot placement thanrequired, for example, can result in the body fall-ing laterally.99

Deficits in balance and walking may contributeto the high reported incidence of falls in cerebellarataxia.82 However, the causes of falls are oftenmultifactorial and the relative contribution ofintrinsic and extrinsic (environmental) factors infalls aetiology in cerebellar dysfunction remainsto be elucidated.

Oculomotor controlNormal 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 riseto well-recognized (and recognizable) oculomotor‘syndromes’111 that may or may not occur togetheror be associated with other cerebellar signs.111–113

These syndromes can be useful diagnostic clues andmay account for visual symptoms (oscillopsia, dizzi-ness, diplopia).114 However, due to the heavy con-nections with the brainstem, oculomotor centres inthe pontomedullary junction (horizontal eye move-ments) and the midbrain (vertical and torsional eyemovements), it is often not possible to differentiatebetween brainstem and cerebellar lesions.

The flocculus/paraflocculus controls the modu-lation of retinal image motion (retinal slip) andmaintains steady fixation in eccentric gazedirections (the neural integrator), accuratesmooth pursuit, optokinetic nystagmus andnormal vestibulo-ocular reflex gain. Visual inputfrom 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 clinicalsigns of the ‘floccular syndrome’ are gaze-evokednystagmus on lateral gaze and jerky (saccadic)smooth pursuit (ipsiversive to the lesion).115–121

Rebound nystagmus may also be present.Vestibulo-ocular reflex suppression is impairedwhich can be readily detected by the failure of a(seeing) patient to suppress post-rotatory vestibu-lar nystagmus.122–127

Vertical eye movements may be normal, butin progressive disorders downbeat nystagmusemerges.128 Acute or chronic alcoholism mayyield similar signs and may be irreversible.Downbeat nystagmus can give rise to constantoscillopsia (the illusion of oscillation of thevisual surround) and poor visual acuity that isunrelated to head movement and position.113

Abnormalities in the direction and in the gain(both increases and decreases) of the angularand linear vestibulo-ocular reflex have beenreported.125,129–135 Abnormalities in the vesti-bulo-ocular reflex can degrade visual acuity withhead motion. Vertical translational head motion isespecially prominent while walking, and abnor-malities in the vertical vestibulo-ocular reflexmay 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 slowphase being generated by the vestibulo-ocularreflex with the fast phase serving to repositionthe eyes centrally in the orbit. The head velocitysignal derived from vestibular nerve afferentsis felt to be stored within brainstem circuits.Evidence for this storage mechanism comes fromthe observation that with a constant velocity rota-tion in the dark, the velocity of the slow phasedecays exponentially with a time constant of�15–20 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 thevestibular time-constant beyond normal, and canlead to periodic alternating nystagmus, in whichthe horizontal jerk nystagmus spontaneouslyreverses direction with a period of tens of sec-onds.111 Periodic alternating nystagmus is oftenmissed due to the need to observe nystagmus forsome minutes. Midline cerebellar lesions can alsoalter the time constant of perceptual vestibular-mediated self-motion.137

The dorsal vermis and fastigial nucleusThe dorsal vermis (lobules 6 and 7) and the fastigial

nucleus are important for the calibration of saccades.The ‘vermis syndrome’ is characterized by saccadehypo- or hypermetria.122,138,139 Detection of dysme-tria requires careful observation, but extreme hyper-metria may give rise to saccadic oscillations (distinctfrom nystagmus) and is suggestive of a nuclear lesion.Smooth pursuit and slow vergence movements mayalso be affected; in particular the velocity of diver-gence is reduced.140 In children, congenital oracquired vermian lesions also lead to difficulties intriggering saccades (‘saccade initiation failure’ or‘congenital ocular motor apraxia’) which is oftenassociated with speech apraxia due presumably toco-involvement of vermian speech areas (see sectionon Dysarthria, communication and language).

Saccade speed appears not to be controlled bythe cerebellum, and saccades that are clinically rec-ognizable as being slow are usually caused bybrainstem disease or drug toxicities.

Vertigo may be experienced secondary to lesionsaffecting the midline vermis and flocculonodularlobe.141,142 Prolonged isolated vertigo with imbal-ance that mimics symptoms of vestibular neuritismay be observed in �10% of cases of discrete cer-ebellar lesions. These most commonly affect themedial branch of the posterior inferior cerebellarartery territory.143 Vertigo may also be positionaland accompanied by positional evoked nystag-mus,142,144,145 thus mimicking benign paroxysmalpositional vertigo. In contrast to benign paroxys-mal positional vertigo, the nystagmusmay be eithervertical (up or downbeat) or torsional in directionwith the eyes straight ahead, be persistent andchange in direction with different head positions.146

Additional signs that may alert the clinician to thepresence of a central cause of vertigo include thepresence of skew deviation, gaze evoked nystagmustowards the affected ear (in the opposite directionto that seen with peripheral vestibular neuritis),vertical saccadic pursuit; a normal head thrusttest and minimal increase in the slow phase velocityof sponataneous nystagmus in the dark comparedto fixation in the light as well as the presence ofassociated neurological signs such as dysmetria/dysynergia or dysarthria.147,148

Dysarthria, communication and languageDysarthria is commonly observed with lesions

affecting the rostral paravermal region of the ante-rior lobes.3,149–151 Impairments in both articu-lation and prosody have been described.152

Commonly speech is described as scanning innature consisting of hesitations, accentuation ofsome syllables and the addition of pauses or omis-sion of appropriate pauses; in around 50% ofcases slurring may be evident.153 In addition,speech can be reduced in rate, and show signs ofvocal instability, increased monotony, equalizedstress and imprecise consonants.154 Acoustic anal-ysis reveals more variable/longer syllable produc-tion and pause durations, reductions in vowellength contrasts and differences in the frequencyspectrum from those in healthy controls.154–156

Speech intelligibility may be affected by difficultiesin distinguishing the difference between plosives(e.g. [p], [t], [k]) at the end of words.157


Kinematic analysis of oro-facial movementshighlights similar changes as previously describedfor limb movements, such as prolongation ofmovement duration; decreased maximal velocityand prolonged muscle bursts.158–160 Furthermore,a 3Hz ‘postural’ tremor may be detected duringsustained phonation of vowels161 and oral disdia-dochokinesia can be detected during rapid syllablerepetition,162 although this may not predict thesyllabic rate during sentence production.163

Language impairments that are not attributedto dysarthria, such as poor understanding ofspeech, reading and naming tasks, and agramma-tism have been reported following cerebellardamage164,165 (although see ref. 166). These arefelt to arise from disruption to reciprocal path-ways between the right cerebellar hemisphere andleft cerebral hemisphere and highlight the role ofthe cerebellum in pre-articulatory speech.167,168

Mutism following posterior fossa tumour resec-tion in children has also been described in about29% of cases.151,169,170 The mutism may notdevelop immediately and is usually self-limiting.170

Here damage to the vermis has been impli-cated,151,169 although cerebellar damage leadingto a temporary reduction in activity in the inter-connected cerebral cortex has also beensuggested.151,171,172

Non-motor symptomsIn the last two decades accumulating evidence

suggests that isolated damage to the cerebellummay also result in a cerebellar cognitive affectivesyndrome.173 This syndrome includes non-motorsymptoms such as poor executive function (e.g.reduced verbal fluency and working memory);impaired spatial cognition (eg poor visuo-spatialmemory) and linguistic difficulties (e.g. dysproso-dia and agrammatism) and has been described inboth acquired and hereditary cerebellar dysfunc-tion.174–180 The symptoms are more marked in theacute/subacute stages of damage/dysfunction, par-ticularly when the posterior lobes of the cerebel-lum are affected bilaterally (e.g. following aninfarction within the posterior inferior cerebellarartery territory). Further, affective symptomssuch as apathy and disinhibited behaviour mayoccur with damage to the midline vermis.181,182

These symptoms are felt to reflect damage to theextensive 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 ongoingcontrol of motor function may therefore have acorollary in non-motor behaviours.181

Such non-motor symptoms may further impacton rehabilitation, for example, by affecting theability to retain information conveyed throughverbal or visual instructions; to perform abstractreasoning or to initiate activities.183,184

Implications for rehabilitationapproaches

As highlighted in recent systematic reviews of ran-domized controlled trials there is currently a lackof high-quality research studies into the rehabili-tation of cerebellar ataxia.185,186 Despite this, theliterature on the treatment of cerebellar ataxiadescribes some approaches that warrant furtherinvestigation. Approaches may be broadly dividedinto those that aim to improve functional abilityby compensating for the underlying deficit andthose that aim to improve function through restor-ative techniques that involve adaptation andrecovery within the neuro-musculoskeletal system.

Compensatory approachesCompensatory approaches include the use of

strategies to encourage decomposition of move-ment into simpler single joint movements187;visual and verbal cues to aid walking speed andstride length188,189; the use of assistive technologyto aid computer use190; and aids such as custom-ized seating and frames to help posture, balanceand mobility.191–193

Increasing the visco-elastic resistance or theinertia of a limb will dampen the tremor andserve to decrease the speed and size of the stretchreflex that may drive the tremor in somecases.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 beenrecommended although their effectiveness hasnot been thoroughly investigated. The visco-elastic


resistance offered by Lycra garments195 may alsounderlie their proposed use in improving proxi-mal and truncal stability and function in peoplewith cerebellar signs. However, any functionalimprovements with Lycra garments in reportedsingle-case studies to date need to be consideredalongside 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 appendicularor axial skeleton may also dampen tremor andreduce dysmetria.63,197,198 Studies into the effec-tiveness of weights in improving upper limb func-tion are variable, with improvements anddeterioration in function as well as a lack ofeffect being reported.49,199–201 This may be becausethe addition of a load requires adaptive scaling ofagonist–antagonist activity which is affected incerebellar disease. Thus, although an increase inagonist activity required to initially accelerate thelimb may be seen, this may not be accompanied byan increase in antagonist ‘braking’ activity.Ultimately, this results in an increase in overshoot-ing and potential deterioration in function.201 Infact the use of additional load may be beneficial asan assessment aid in revealing minimal hyperme-tria.202 Loading the trunk may aid balance, andhere the loading may be either symmetrical orasymmetrical to counterbalance a directionalimpairment in balance (e.g. anterior loading isprovided to counterbalance falling backwards).Although it is not always clear whether theataxia is of pure cerebellar origin, case reports ofthese interventions show a favourable outcome onclinical measures of walking and balance.197,203,204

Cooling a limb can also temporarily reducecerebellar tremor. This may occur through areduction in muscle thixotropy and increase inmuscle stiffness as well as a reduction in nerveconduction velocity and muscle spindle afferentfeedback.205,206 Cooling-related reductions intremor resulting in functional improvements havealso been reported in people with essentialtremor.207,208

Restorative approachesThe uses of defined restorative approaches tar-

geting a specific symptom are rare and involve

uncontrolled case reports. With prolonged inter-ventions (3–12 months) improvements in inter-limb coordination209,210 and a reduction in forcevariability have been described.191 Biofeedback ofdifferent aspects of motor control has beenassessed. Biofeedback of EMG patterns during avisuomotor tracking task led to an improvementin muscle activation on the trained task after sev-eral weeks of training although the effects on func-tional tasks were not investigated.211 Biofeedbackof muscle activity has also been described in com-bination with relaxation therapy to decreasetremor resulting in improved feeding.212,213

Biofeedback of the centre of pressure motion (ameasure of postural sway) linked to a computergame resulted in improvement in measures of bal-ance and falls and the use of a computer game waslinked 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 systematicreviews.185,186 Balance and ocular exercises haveled to an improvement in clinical measures of pos-tural stability and walking in people with cerebel-lar ataxia.215 Although this study involved smallnumbers (n¼ 2), the techniques utilized are basedon those that are effective in treating deficitsaffecting the peripheral and central vestibularsystem with which the cerebellum has large recip-rocal connections. Brown et al.216 also used vestib-ular habituation training in combination withstrengthening, stretching and gait re-education.Significant improvements in disability scales(Disability Handicap Inventory; Dynamic GaitIndex) were seen in the subgroup of people withcerebellar ataxia (n¼ 10). Increases in walking dis-tance following either locomotor training usingbody weight support on a treadmill (5 days/weekfor four months) or by encouraging people todecrease the amount of fixation of the armswhen walking217,218 have been reported.

Improvements in standing balance have alsobeen seen with a combination of strength andbalance exercises.219,220 Both groups utilizedFrenkel’s exercises that were originally developedfor people with sensory ataxia secondary to tabesdorsalis (Frenkel, 1902). These exercises emphasizea 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 wouldbe interesting to contrast the reliance of differentsensations on balance following this approach withthat seen after the vestibular habituation/rehabili-tation exercises described above.Several small-scale studies on training ocular

control and dysarthria highlight the potentialvalue of further intervention studies in theseareas. In a stepping task that defined the targetfor foot placement, Crowdy et al. found that sac-cadic and foot placement accuracy could beimproved by prior practice in making saccadiceye movements towards the targets.223 A single-case study of a person with cerebellar dysfunctionsecondary to thiamine deficiency assessed theeffects of Lee Silverman voice treatment. Thisapproach emphasizes loudness of phonation andis more commonly used in the treatment of peoplewith Parkinson’s disease. After a four-week inter-vention period (16 sessions), improvements inacoustic measures (sound pressure level) and per-ceptual measures of articulation/phonation wereobserved and their employer reported increasedsatisfaction 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 showingthat cerebellar dysfunction results in a reduction inmeasures of motor cortex excitability.225–234 Kochet al. investigated the effect of rapid transcranialmagnetic stimulation (5Hz) over the motor cortex.The frequency and paradigm of stimulation usedhad previously been shown to result in an increasein motor cortex excitability and was associated inthe cerebellar ataxic group with an improvementin hand function (as determined by the 9-hole pegtest) compared to healthy controls.235

Direct stimulation of the cerebellum hasalso been investigated. Stimulation of the cerebel-lum using transcranial magnetic stimulation inhealthy participants has also been shown to mod-ulate cortical excitability.236–244 In people withspinocerebellar 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 thefact that transcranial magnetic stimulation overthe cerebellum may in part affect motor cortexexcitability by stimulating adjacent peripheralnerves.247,248

Understanding when to apply restorative orcompensatory strategies remains unclear. The rel-ative use of compensatory strategies may vary andpossibly depends on disease progression andseverity.

Potential mechanisms and barriersto recovery

The potential mechanisms of recovery followingcerebellar damage have not been extensively stud-ied. The results of serial experimental cerebellarlesions in primates suggest that following unilat-eral cerebellar lesions, important structuresmediating recovery are the opposite cerebellarhemisphere, deep cerebellar nuclei, as well asextracerebellar sites within the brainstem and sen-sorimotor cortex, the latter depending on whethervolitional limb movements or walking/balance isbeing investigated.249–253 Extrapolation of suchfindings to humans should be made with cautiondue 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. Resolutionof such disachisis may also underlie symptomrecovery.256,257 In humans with cerebellar dysfunc-tion, for example, an increase in the activation ofthe medial premotor system (supplementary motorarea) while moving has been reported; this maycompensate for the lack of activation of the lateralpremotor areas that receive extensive inputs fromthe cerebellum.258 Furthermore, following a uni-lateral lesion, imbalances in activity between leftand right cerebellum and their interconnected cor-tical structures may also contribute to symptompresentation. Torriero et al. hypothesized thatisolated damage to the left cerebellum mayreduce excitatory drive to the contralateral rightdorsolateral prefrontal cortex, resulting in animbalance in activity between the left and right


cortex. Re-addressing this imbalance temporarilyby inactivating the left dorsolateral prefrontalcortex using rapid transcranial magnetic stimula-tion resulted in an improvement in a procedurallearning task.259 Such findings are in keeping withevidence from subcortical stroke, where changes ininterhemispheric inhibition from the unaffected tothe affected side may contribute to paresis.260

The cause, site and extent of the lesion areimportant predictors of the degree of functionalrecovery. Functional deficits seem more markedfollowing a haemorrhage compared to an infarct,and superior cerebellar artery strokes have a worseprognosis than strokes affecting the posterior andanterior inferior cerebellar arteries261,262 (althoughsee ref. 263). Superior cerebellar artery strokesmay be associated with damage to the dentatenucleus and the superior cerebellar peduncle, themain output pathway of the cerebellum. This is inkeeping with other studies highlighting worsefunctional recovery with lesions affecting theoutput pathways of the deep cerebellar nucleiand superior cerebellar peduncle.70,264

Extracerebellar damage seems to be a poorprognostic indicator of functional recovery.265

Functional recovery after a cerebellar stroke, forexample, is worse when people initially presentwith global signs such as loss of consciousness/weakness, as opposed to isolated focal signs suchas ataxia or vertigo.261,266,267 Following stroke,increasing age is also associated with worse func-tional outcome,267 although this may in part beexplained by the association of age-related addi-tional extracerebellar white matter lesions.268

Against an effect of age on prognosis is the findingthat the ability to compensate for a cerebellartumour post resection does not seem to be betterin young children (54 years old) than in older chil-dren, adolescents and adults.264,269

In other pathologies the presence of additionalcerebellar dysfunction strongly impacts on recov-ery. The recovery from a peripheral vestibularnerve lesion and the recovery from a brainstemstroke is less pronounced in the presence of anadditional cerebellar lesion.270,271 This maysimply reflect an increasing accumulation ofpathology. However, it may also reflect that thecerebellum normally plays an important role inmotor learning and the recovery of symptoms

following damage to other central and peripheralnervous system structures.

Motor learning, adaptation and recoveryThe role of the cerebellum in motor learning is

being investigated at a subcellular, cellular and sys-tems level in both animals and humans and usingneural networks andmodelling.18 The cerebellum ispart of a distributed system that is involved inmotor learning and is felt to play a pivotal role inerror-based motor learning and adaptation.272,273

In keeping with this, people with cerebellar ataxiamay show greatly impaired learning of both simpleand complex motor skills such as visuomotor adap-tation,274–276 serial reaction time tasks,277,278 adap-tation to prism glasses279 and force fields,280 as wellas classical conditioning paradigms when the inter-val between the unconditioned and conditionedstimulus is short (�400ms).281–285 Importantly,such adaptation is constantly occurring in everydaylife. Tasks such as adapting the arm to its new‘length’ and dynamics when holding an object(e.g. a pen), adapting the vestibulo-ocular reflexwhen glasses are put on and adapting to the effectsof muscle fatigue286 with repetitive activities allseem to require cerebellar activity.

Poor recovery following a cerebellar lesion maybe a consequence of damaging structures criticallyinvolved in learning and relearning of motor skills.However, following a cerebellar lesion learningand adaptation over time has been described,albeit at a lower rate and extent than that inhealthy controls.73,98,287 It remains to be seenwhether this reflects activity within undamagedareas of the cerebellum or activity in extracerebel-lar structures.

Conclusion

An understanding of the pathophysiology of cere-bellar ataxia and the mechanisms of recovery canhelp to guide the development of treatments andto optimize current interventions. Interpretingstudies of pathophysiology in turn cruciallydepends 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 potentialavenues that warrant further investigation. Futurestudies should aim to identify the site and extent ofboth cerebellar and extracerebellar pathology asthese may crucially determine clinical presentationand prognosis. A detailed description of the per-son’s presenting impairment profile should be cou-pled with appropriate outcome measures of theeffects of intervention on a person’s ability andparticipation.

Clinical messages

� The key role of the cerebellum in motorlearning and in adaptation following extra-cerebellar pathology may limit functionalrecovery in people with cerebellar dysfunc-tion.

� Associated cognitive and affective signs mayfurther impact on function and the rehabili-tation process.

� There is limited evidence about the effective-ness of interventions in people with cerebellardysfunction although clinical improvementsin balance, walking and upper limb functionhave been reported. A combination ofrestorative and compensatory techniquesmay be utilized; the relative emphasisdepending on the severity of cerebellarataxia and its pattern of progression.

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