doi:10.

1093/brain/awh560 Brain (2005), 128, 1480–1497

REVIEW ARTICLE
Apraxia in movement disorders
Cindy Zadikoff and Anthony E. Lang

Morton and Gloria Shulman Movement Disorders Center, Toronto Western Hospital, University of Toronto,
Toronto, Ontario, Canada
Correspondence to: Dr Anthony E. Lang, Morton and Gloria Shulman Movement Disorders Center, McL-7,
Toronto Western Hospital, 399 Bathurst Street, Toronto, ON, Canada, M5T 2S8
E-mail: [email protected]

The definition of apraxia specifies that the disturbance of performed skilled movements cannot be explained by
the more elemental motor disorders typical of patients with movement disorders. Generally this does not
present a significant diagnostic problem when dealing with ‘higher-level’ praxic disturbances (e.g. ideational
apraxia), but it can be a major confound in establishing the presence of limb-kinetic apraxia. Most motor
disturbances characteristic of extrapyramidal disorders, particularly bradykinesia and dystonia, will comprom-
ise the ability to establish the presence of loss of dexterity and deftness that constitutes this subtype. The term
‘apraxia’ has also been applied to other motor disturbances, such as ‘gait apraxia’ and ‘apraxia of eyelid opening’,
that perhaps are misnomers, demonstrating the lack of a coherent nomenclature in this field. Apraxia is a
hallmark of corticobasal degeneration (CBD) and historically this has received the most attention among the
movement disorders. Corticobasal degeneration is characterized by various forms of apraxia affecting limb
function, particularly ideomotor apraxia and limb-kinetic apraxia, although buccofacial and oculomotor apraxia
can be present as well. The syndrome of parkinsonism and prominent apraxia, designated the ‘corticobasal
syndrome’ (CBS), may be caused by a variety of other central nervous system pathologies including progressive
supranuclear palsy (PSP), Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementias.
Distinct from the CBS, PSP and Parkinson’s disease can demonstrate varying degrees of apraxia on selected
tests, especially in those patients with more severe cognitive dysfunction. Diseases that cause the combination
of apraxia and a primary movement disorder most often involve a variety of cerebral cortical sites as well as
basal ganglia structures. Clinical-pathological correlates and functional imaging studies are compromised by
both this diffuse involvement and the confusion experienced in the clinical evaluation of apraxia in the face of the
additional elemental movement disorders. Finally, although apraxia results in clear disability in patients with
the CBS, it is not clear how milder ideomotor apraxia found on specific testing contributes to patients’ overall
day-to-day motor disability.

Keywords: apraxia; corticobasal degeneration; Huntington’s disease; movement disorders; Parkinson’s disease;
progressive supranuclear palsy

Abbreviations: ALO = apraxia of eyelid opening; CBD = corticobasal degeneration; CBS = corticobasal syndrome;
DLB = dementia with Lewy bodies; IMA = ideomotor apraxia; LKA = limb-kinetic apraxia; MSA = multiple system atrophy;
OFA = orofacial apraxia; PSP = progressive supranuclear palsy
Received November 1, 2004. Revised March 10, 2005. Accepted May 12, 2005. Advance Access publication June 1, 2005

Introduction
Apraxia covers a wide spectrum of disorders that have in be superimposed on elementary motor disorders such as
common the inability to perform a skilled or learned act weakness, bradykinesia, rigidity, tremor, dystonia and ataxia
that cannot be explained by an elementary motor or sensory (Heilman, 1985; Roy and Square, 1985; Poizner et al., 1990,
deficit or language comprehension disorder. Praxis errors 1995). In many higher order apraxic disorders, such as
have been well defined clinically and kinematically and can ideational apraxia, this does not usually pose a diagnostic
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Apraxia in movement disorders Brain (2005), 128, 1480–1497 1481

dilemma. Although bradykinesia and other extrapyramidal correctly. It is classified by both the nature of the errors made
signs (e.g. rigidity or dystonia) might cause a delay in initi- and the means by which they are elicited. For instance, abnor-
ation or performance of a gesture, the quality of the gesture mal performance can be due to ‘temporal errors’ (such as
should not be affected by these and so gestural impairment impaired timing and poor sequencing of a movement that
could not be explained by their presence alone. However, in requires multiple positionings, as long as the overall content
some cases, such as those with limb-kinetic apraxia (LKA), of the movement remains recognizable), ‘spatial errors’ (such
bradykinesia and rigidity could readily compromise the ability as abnormal amplitude, internal or external configuration
to distinguish the loss of dexterity and coarseness of move- orientation and body-part-as-object substitution), ‘content
ment that characterize this subtype. In this review we will errors’ (such as perseveration) or ‘other errors’ (such as
begin with a summary of the basic types of apraxia and the lack of response or an entirely unrecognizable response)
underlying neuroanatomical and physiological mechanisms (Rothi et al., 1988). Since Liepmann’s original description,
thought to play a role, particularly as they relate to diseases of others have tried to advance his model in order to account for
the basal ganglia. We will then discuss the different movement different types of praxis errors. Roy and Square (1985) pro-
disorder syndromes commonly, and not so commonly, asso- posed a two-part model in which a conceptual component
ciated with apraxia. The neurological diseases chosen are encodes an abstract knowledge base for actions, including
based largely on descriptions of apraxia in those conditions information about tool use and sequencing a series of single
in the literature as well as clinical experience. Certain dis- actions, and a production component provides sensorimotor
orders that are called ‘apraxia’, such as eyelid opening apraxia information on how to perform an action ‘programme’ and
(ALO), but are probably better classified separately from then translates these programmes into actions. Much of our
apraxia, are also addressed. understanding of apraxia is based on lesioning studies and yet
no single area alone has consistently been involved in the
production of apraxia. This suggests that praxis functions
are distributed through different neural networks working
Overview of apraxia together. Depending on the neural network involved, the
The first contemporary ideas of apraxia stem from the work of types of errors will differ. For example, as pointed out by
Liepmann, who proposed that in order to perform an action, Leiguarda and Marsden (2000), there is a parietofrontal sys-
the motor engram (or ‘space–time plan’) has to be conveyed tem that encodes reaching and grasping mechanisms, and a
from the left parietal lobe via association fibres to the ‘Central frontostriatal system that encodes sequential motor events.
region’, in which Liepmann included the precentral and post- Moreover, the extent to which these systems are affected
central gyri, the middle and superior frontal gyri and their depends on the context of the movement and the cognitive
underlying white matter tracts. The Central region effected demand of the action (Leiguarda and Marsden, 2000). Table
the action through the primary motor cortex, i.e. through the 1, which summarizes the major classification of motor limb
final common pathway of the pyramidal tract. If the left limb apraxias (Rothi and Ochipa, 1991), will serve as a background
is to perform a task, then the information needed to be trans- to the types of apraxia found in movement disorders
mitted through the corpus callosum to the Central region on discussed below.
the right in order to activate the right pyramidal tract to carry
out the action (Liepmann, 1908, 1920). Since that time, many
other studies have confirmed the dominance of the left hemi-
sphere in praxis (Basso et al., 1980; De Renzi et al., 1980, Role of the basal ganglia and apraxia
1982). Apraxia, as tested by imitation and object use panto- The motor and premotor areas of the cortex send projections
mime, has been found in 50% of patients with left hemi- to the basal ganglia (Alexander et al., 1986), as do areas of the
sphere damage and in <10% with right hemisphere damage. parietal cortex that are interconnected with those areas of the
This suggests that many patients have bilateral representation motor cortex, making up the parietofrontal circuits. These
of praxis functions (De Renzi, 1989). Even Liepmann pointed circuits act in parallel. Each one is involved in sensorimotor
out that the right hemisphere probably has some praxis skills, integration or in the translation of specific sensory data into
and this has been used to explain why there is sparing of information for movement production (e.g. visual and soma-
certain left-hand praxis functions after callosal or left hemi- tosensory transformation for reaching and body part location
sphere lesions (Geschwind and Kaplan, 1962; Graff-Radford data for control of body part movements). There are also
et al., 1987). distinct frontostriatal circuits that play a role in action
Damasio and Geschwind (1985) defined apraxia as dem- sequencing. The circuit activated depends on whether the
onstrating varying combinations of the following disturb- action to be performed is prelearned or new, and on the
ances in order of progressive dysfunction: the failure to complexity of the cognitive demands of the task (Grafton
produce the correct movement in response to a verbal com- et al., 1995; Catalan et al., 1998). Apraxia can be found in
mand, the failure to correctly imitate a movement performed diseases of the basal ganglia, including Parkinson’s disease,
by the examiner, the failure to perform a movement correctly progressive supranuclear palsy (PSP) and Huntington’s dis-
in response to a seen object and the failure to handle an object ease, and reportedly in isolated lesions of the basal ganglia.
1482 Brain (2005), 128, 1480–1497 C. Zadikoff and A. E. Lang

Table 1 Summary of apraxia types

Apraxia type Definition Clinical testing Localization

Limb-kinetic Loss of hand and finger All movements are affected—symbolic, All pathologically confirmed cases have
dexterity resulting from non-symbolic, transitive (i.e. using tools shown a degenerative process involving
inability to connect or and instruments, e.g. a hammer or a frontal and parietal cortices (Fukui et al.,
isolate individual movements hairbrush) and intransitive 1996) or primary motor cortex
(Kleist, 1907) (i.e. communicative gestures, (Tsuchiya et al., 1997)
e.g. representational tasks such as
waving goodbye and
non-represenational tasks such as touch
your nose and wiggle your fingers)
Mainly distal in finger and hand
Movements are coarse and mutilated
No voluntary automatic dissociation:
Ideomotor Disorder of goal-directed Impairment of pantomiming ability to Anatomically diverse lesions mainly in
movement. Patient knows use tool. Movement is incorrectly left hemisphere; typically involve parietal
what to do but not how to do produced but the goal of the action can association areas and white matter
it. Disturbance of timing, usually be recognized. Abnormal errors bundles connecting frontal and parietal
sequencing and spatial include spatial errors [i.e. (i) abnormal association areas. Less commonly
organization of gestural amplitude; (ii) body-part-as-object premotor and supplementary motor
movement (Rothi and substitution, e.g. the patient uses his cortex are involved as well as basal
Ochipa, 1991) own finger to represent a toothbrush ganglia and thalamus. Unilateral lesions
when asked to brush his teeth; of the left hemisphere in right-handed
(iii) abnormal orientation of body part patients produce bilateral deficits,
performing the action, e.g. when the usually less severe in the left than in
patient is asked to pantomime brushing the right limb
his teeth he closes his fist tightly with no
space for the imagined toothbrush
handle or he may hold his hand right
next to his mouth without
demonstrating the distance necessary to
accommodate the imagined toothbrush]
and temporal errors (i.e. irregular
timing, which can be either an increased
or decreased rate of production of a
pantomine and sequencing
abnormalities, e.g. an addition, deletion,
or transposition of movement parts as
long as the overall movement structure
remains recognizable) (Rothi et al.,
1988). Improves on imitation and with
use of actual tool. Transitive more
affected than intransitive. Voluntary
automatic dissociation is present,
so that deficit is more apparent in
clinical setting than in everyday life.
Ideational/ Patient does not know what Inability to perform a multiple-step task No one anatomical area has been
conceptual to do. Content errors. This (e.g. prepare a letter to mail) owing to identified, although in focal hemispheric
terminology can be confusing errors such as perseveration. lesions, most have damage to left
not only because definitions Disturbance of single tool use—cannot hemisphere. Damage typically thought
of ideational and conceptual associate tool and object with the to involve left parieto-occipital and
apraxia vary among authors corresponding action (e.g. unable to parietotemporal regions (Liepmann,
(Ochipa et al., 1992; DeRenzi choose a hammer to drive a nail or 1920) but can also involve left frontal,
and Lucchelli, 1988) but also correctly pantomimes an action when frontotemporal and temporal regions
because a distinction between requested to perform a very different with or without subcortical involvement
the two is debated by some. one) (Roth et al., 1988; Leiguarda et al., (Heilman et al., 1997)
Error types include, 2000a; Ochipa et al., 1992)
impairment in carrying out
sequences of actions requiring
the use of various objects in
the correct order so as to
achieve an intended purpose
(Liepmann, 1920), and loss of
tool action knowledge
Apraxia in movement disorders Brain (2005), 128, 1480–1497 1483

Thus it seems likely that the basal ganglia are involved in disease, then all patients with Huntington’s disease should
the transformation of action plans, or movement formulas, exhibit apraxia. Rather, those with longer disease duration
to motor acts and, therefore, that dysfunction of the basal exhibited apraxia, again suggesting that apraxia is secondary
ganglia itself could lead to errors of praxis. to damage to the basal ganglia plus other structures such as
Animal and human studies, using both electrophysiology surrounding white matter (Hamilton et al., 2003).
and functional imaging, have tried to define the role of the The suggestion that dysfunction of the basal ganglia alone is
basal ganglia in producing apraxia. Experimental studies in insufficient to cause apraxia is further supported by the work
monkeys have shown that putaminal lesions cause inaccurate of Pramstaller and Marsden (1996), who reviewed 82 cases of
reaching (Kendall et al., 2000) and globus pallidus internus ‘deep’ apraxia as a result of defined lesions, using imaging
lesions cause impaired reaching and grasping (Wenger et al., (CT, and MRI if available) in 73 and neuropathological cor-
1999). Furthermore, positron emission tomography studies in relation in 9. They found that most had lesions in the left
humans have found activation of the caudate/anterior puta- hemisphere, that isolated lesions of the putamen, thalamus, or
men during the performance of new or complex learned lenticular nucleus were uncommon (8 out of 82) and that
sequences and activation of the middle putamen during most patients actually had larger lesions involving damage to
the performance of automatic sequences (Jueptner and Weil- the basal ganglia and/or thalamus as well as to the peri-
ler, 1998). Electrophysiological studies have shown that there ventricular and peristriatal white matter, disrupting associ-
are subsets of neurones in the external and internal segments ation fibres. In fact no cases of pallidal lesions alone caused
of the globus pallidus and substantia nigra pars reticulata that apraxia, and lesions of the caudate which caused apraxia
increase their discharge frequency in relation to the amplitude (n = 3) all had white matter involvement. Limb IMA was
and velocity of movements (Georgopoulos et al., 1983) the most common type of apraxia described (72/82), followed
whereas other pallidal neurones fire in relation to the direc- by orofacial apraxia (OFA) in association with IMA (n = 37)
tion of arm movement (Mitchell et al., 1987). Moreover, there (Pramstaller and Marsden, 1996). Thus, as stated above,
are yet other pallidal neurones that change activity in although the basal ganglia may be involved in the production
remembered sequential tasks and are influenced by the con- of learned, skilled motor acts, it seems unlikely that isolated
textual setting of the movement. This suggests that the basal lesions in the basal ganglia are capable of producing the dis-
ganglia are involved in the production of both new and turbances of motor performance subsumed under the concept
learned movement sequences. of apraxia. Rather, the basal ganglia alters the expression of
Using three-dimensional analysis, Leiguarda and colleagues apraxia based on the context of movement required.
(2000b) studied the kinematic properties of a bread-slicing
movement in patients with Parkinson’s disease, PSP and mul-
tiple system atrophy (MSA). This task was chosen in part Disorders possibly misdesignated as
because of the repetitive, precise spatial movements required apraxia
to successfully complete it, recognizing that the basal ganglia Since the term apraxia was first coined, many conditions have
play a part in such movements. As will be discussed below, been called ‘apraxia’. If the current definition of apraxia is
two of the five patients with PSP, two of the eight with applied, some conditions have probably been erroneously
Parkinson’s disease, and none of the five MSA patients designated as apraxias. Based on the literature, varying the-
were felt to have ideomotor apraxia (IMA) clinically. Subjects ories can be advanced as to the pathophysiology underlying
in all groups made some spatial errors, although the errors these, although more work is needed to better classify them.
made by the apraxic patients were more severe. The authors Two—apraxia of eyelid opening and apraxia of gait—are
felt that the milder errors in movement trajectory and external commonly seen in movement disorder patients and will be
configuration found in their patients supported the role of the discussed below. Limb-kinetic apraxia, which to some repres-
basal ganglia as an integral component of a brain network for ents an elemental motor disturbance rather than a true
praxis. Additional damage to this network by extension of apraxia, will be discussed in the section on corticobasal degen-
pathology beyond the basal ganglia might then result in clin- eration (CBD).
ically overt IMA, as seen in a subgroup of their patients.
Mink (1996) described the role of the basal ganglia in terms ‘Apraxia’ of eyelid opening
of a gate that moderates response choice by selectively inhib- Apraxia of eyelid opening is a syndrome characterized by the
iting competing input from the cortex. As such, basal ganglia inability to voluntarily open the eyes. The underlying patho-
lesions could disrupt the organized production of purposeful physiology of ALO is not well understood, as evidenced by the
movement by flooding the system with competing response numerous other proposed designations, including inhibition
options (Mink, 1996). Supporting this notion is a study on of levator palpebrae (Lepore and Duvoisin, 1985; Fahn, 1988),
apraxia in Huntington’s disease, which found that apraxia akinesia of lid opening (Fahn, 1988) and lid freezing (Jankovic
was related to disease severity. The authors postulated that et al., 1990). Goldstein and Cogan (1965) described the dif-
apraxia in this situation was due to an inability to effectively ficulty in initiating the act of lid elevation in four patients with
gate competing motor programmes. If this was due to caudate basal ganglia disease and subsequent reports emphasized the
damage alone, which is typically seen early in the course of the presence of this syndrome in extrapyramidal disorders, in
1484 Brain (2005), 128, 1480–1497 C. Zadikoff and A. E. Lang

particular PSP (Lepore and Duvoisin, 1985; Krack and associated or accompanying feature. Although tradition
Marion, 1994; Boghen, 1997). There is considerable support will continue to encourage the use of the term ‘apraxia of
for the classification of many cases as a form of focal eyelid eyelid opening’, the weight of evidence supports not classify-
dystonia. It is frequently found in association with blepharos- ing this as a form of apraxia.
pasm, and rarely occurs as an isolated entity (Elston, 1992). In
one population study ALO coexisted with adult-onset bleph-
arospasm in 75% of cases and with atypical parkinsonism in ‘Apraxia’ of gait
25% (Lamberti et al., 2002). Among the overall patient popu- ‘Apraxia of gait’ is another term that perhaps is a misnomer. It
lation seen in the authors’ movement disorders clinic, it was is distinct from ‘leg apraxia’, and often the two do not coexist.
isolated in 10 patients, associated with adult-onset dystonia in Leg apraxia can be tested using similar concepts to those that
13 (10% of all of their patients) and with parkinsonian syn- guide examination of the upper limb. The patient can be asked
dromes in 9 patients (2% of their parkinsonian patients; a to pantomime tasks such as kicking a ball or stubbing a
third of these had PSP). Recently ALO has been reported in up cigarette out with a foot. However, leg apraxia has not
to 31% of patients undergoing subthalamic nucleus deep been routinely well studied in the assessment of praxis, and
brain stimulation for Parkinson’s disease (Krack et al., 2003). most of the literature on apraxia concentrates exclusively on
In patients with isolated ALO, the complaint is generally the upper limb. This is in part because there is no standardized
the inability to open the eyes and not the forceful closure of testing of the lower limb and in part because there are fewer
the eyes that constitutes blepharospasm. In one series (Krack movements (especially complex tasks) that can be tested in the
and Marion, 1994), apraxia of eyelid opening, referred to as lower limb.
‘focal eye dystonia’ by the authors, was seen in two patients In contrast to the infrequent mention of leg apraxia,
with parkinsonism responsive to levodopa but in whom focal ‘apraxia of gait’ has garnered considerable attention; however,
dystonia (spasmodic torticollis and blepharospasm) preceded the literature on this topic is quite complex, with various
the onset of parkinsonism. No ALO was seen in over examples of lumping and splitting ‘higher order’ gait dis-
200 patients with idiopathic Parkinson’s disease without pre- orders (commonly with overlapping features using different,
ceding dystonia. Further support for considering it a form of often confusing, terminology). For instance, whereas some
dystonia is the fact that some patients can use sensory tricks, assume that the terms ‘marche a petit pas’, ‘lower body
such as touching the sides of their eyes, to help initiate eyelid parkinsonism’, ‘vascular parkinsonism’, ‘Bruns’ ataxia’ and
opening and that many of the same triggers that aggravate ‘gait apraxia’ all represent a similar gait subsumed under
typical blepharospasm, such as bright light and looking up, the umbrella term ‘frontal gait disorders’ (Geschwind,
are also present in ALO. The response of ALO to treatment 1975; FitzGerald and Jankovic, 1989; Schiller, 1995; Elble
with botulinum toxin in many patients also favours the con- et al., 1996), others have used this term to refer to different
sideration of dystonia rather than a form of apraxia. Excessive gait patterns including frontal disequilibrium, isolated gait
activity isolated to the pretarsal component of orbicularis ignition failure and freezing of gait (Geschwind, 1975; Nutt
oculi probably accounts for both the absence of forced eyelid et al., 1993; Poizner et al., 1995). Nutt et al. (1993) referred to
closure in many and the response to botulinum toxin all of these gait disturbances as ‘higher level gait disorders’ to
(Jankovic, 1996; Defazio et al., 1998). signify dysfunction of the highest integrative sensorimotor
However, dystonia is unlikely to account for all cases of systems with intact basic motor and sensory functions. In
ALO. Inappropriate inhibition of the levator palpebrae mus- classifying these disorders they mixed clinical phenomenology
cle also seems to play an important role in the inability to (gait ignition failure) with anatomical location (‘frontal gait
initiate eye opening in some patients with ALO. In a study disorder’). In contrast, Liston et al. (2003) tried to avoid this
(Aramideh et al., 1994) of five patients referred for botulinum potential confound by simply classifying all ‘higher level gait
toxin injections for ‘blepharospasm’ (four with blepharos- disorders’ (they limited their discussion to vascular causes) as
pasm and levator inhibition and one with isolated levator apraxic gaits and naming them according to the primary
inhibition), the patient with isolated levator inhibition did problem seen, namely, ‘ignition apraxia’, ‘equilibrium
not have ongoing spasms of the eyelids but frequently experi- apraxia’ or ‘mixed gait apraxia’. This assumes that all higher
enced involuntary drooping of the lids. No overt abnormal level gait disorders can be considered forms of apraxia; how-
contractions of the orbicularis oculi were noted in this patient; ever, this may not be appropriate. It has been postulated that
electromyography showed no dystonic activity of the orbicu- gait ignition failure (Freeman et al., 1993; Georgiou et al.,
laris oculi, but frequent episodes of inhibition of levator 1993) in Binswanger’s disease and lower body parkinsonism
palpebrae activity were present. Here, as opposed to cases owing to vascular disease occurs when damage to white mat-
with overactivity of pretarsal orbicularis oculi, botulinum ter tracts alters communication between the basal ganglia and
toxin failed to improve ALO. the supplementary motor area, which may be involved in the
Neither of these causes of eyelid opening dysfunction is internal cueing and guidance of learned, skilled, motor acts of
consistent with current concepts of the various types of the limbs (Chang et al., 1992; Hennerici et al., 1994). How-
limb apraxia. Furthermore, when apraxia is evident in ever, ‘gait apraxia’ typically exists without any evidence of
orolingual muscles, eyelid opening difficulties are not an other forms of apraxia and patients with bilateral limb apraxia
Apraxia in movement disorders Brain (2005), 128, 1480–1497 1485

can have a normal gait (Geschwind, 1975; Thompson and (Table 1) (Leiguarda et al., 2000a). This is commonly bilateral
Marsden, 1987). Furthermore, in the strictest of definitions, but typically asymmetrical, especially early in the disease
apraxia is the inability to perform ‘skilled or learned motor course (Rothi et al., 1985). The majority of errors made by
acts’. However, locomotion is not a consciously learned CBD patients with IMA consist of spatial, temporal and
motor act but rather a repetitive motor pattern generated sequencing errors, reflecting disruption of the ‘action produc-
by spinal mechanisms and modified by brainstem structures tion system’ (Leiguarda et al., 2000a). As is also to be expected,
(Shik and Orlovsky, 1976; Armstrong, 1988; Grillner et al., the errors are more frequently observed when performing
1995). One could argue that since walking is more ‘hard transitive than intransitive tasks and often improve when
wired’ there can be no such thing as an apraxic gait. With the subject is given an object to use (Table 1). A number
a better understanding of the underlying anatomical and of different studies (Pillon et al., 1995; Blondel et al., 1997;
functional pathology resulting in the clinical phenomenology, Jacobs et al., 1999) have found that, although patients with
perhaps a more uniformly acceptable nomenclature could be CBD make errors on gesture to command as well as imitation,
devised and current confusion eliminated. most have relative preservation of gesture recognition. Study-
ing a group of healthy volunteers using H215O positron emis-
sion tomography, Peigneux et al. (2004) showed that regional
Apraxia in corticobasal degeneration cerebral blood flow increases in the medial frontal gyrus
Clinical features (supplementary motor area) in the left hemisphere during
Apraxia has been described in a number of diseases of the pantomime to command versus gesture recognition. This
basal ganglia, such as Parkinson’s disease, PSP and Hunting- conforms to anatomical divisions of praxis and the sites of
ton’s disease. Corticobasal degeneration is the disorder most most profound pathological involvement in classical CBD, in
commonly associated with apraxia, which is present in up to which the brunt of cortical pathology is in the superior frontal
70% of patients with clinically diagnosed CBD (Leiguarda and precentral and postcentral gyri (Dickson et al., 2000). For
et al., 1994). Corticobasal degeneration is characterized by example, in a study of patients with IMA resulting from
an akinetic-rigid syndrome combined with asymmetric, anterior and posterior lesions in the left hemisphere, only
lateralizing cortical signs including sensory loss, alien limb those patients with a damaged parietal lobe had impairment
behaviour and apraxia. In fact, apraxia is considered a hall- in the recognition of gestures (Heilman et al., 1982; Rothi
mark of CBD and is an important component of all proposed et al., 1985). The authors concluded that there are anterior
diagnostic criteria (Litvan et al., 2003). However, this then and posterior forms of IMA and that in the former gesture
serves as an important source of clinical bias: a very high recognition is preserved, whereas in the latter it is not. This is
proportion of patients with the clinical diagnosis of CBD because the visuokinaesthetic motor engrams are stored in the
have apraxia because apraxia is believed to be a distinguishing parietal lobe and project to the supplementary motor area.
factor. Of equal importance, it is a source of misdiagnosis: They proposed that the supplementary motor area transcodes
patients with parkinsonism plus apraxia are typically dia- the space–time representation into an innervation pattern and
gnosed as having CBD rather than the more appropriate then projects this information to the primary motor cortex,
designation of ‘cortical-basal syndrome’ (CBS) (Boeve et al., which directs the movement. In parietal lobe damage the
2003; Lang, 2003). The CBS may be caused by a variety of visuokinaesthetic information is disturbed and gesture com-
underlying central nervous system pathologies, including prehension is impaired. In the anterior type of IMA, in which
PSP, Alzheimer’s disease, dementia with Lewy bodies there is damage to the supplementary motor area or to sub-
(DLB) and frontotemporal dementias (see below). cortical white matter which disconnects motor areas from the
In ‘classic’ CBD two types of apraxias have been emphas- intact parietal lobe, the ‘praxicon’ (visuokinaesthetic engram)
ized: ideomotor and LKA. Ideational apraxia has not been is still intact and so patients can recognize gestures easily;
discussed in detail. It has been suggested that this was a late however, the information on how to perform the gesture is
feature related to more severe dementia (Gibb et al., 1990). lost (Heilman, 1985). Now there is evidence from brain
However, since then it has been recognized that dementia may imaging studies in man (Steinmetz et al., 1989; Martin
be a common presenting feature of this disorder (Grimes et al., et al., 1995) that, in fact, action recognition relies more on
1998). Because this subgroup of patients are rarely given the temporal lobe structures than on the parietal lobe. In a study
clinical diagnosis of CBD, the nature of apraxia seen with this comparing gesture recognition in patients with parietal lobe
presentation has not been routinely evaluated. One study that damage to patients with premotor/supplementary motor area
compared features associated with a cognitive presentation damage and normal controls, minimal deficits in gesture
with features associated with an extrapyramidal presentation comprehension were found in the group with parietal lobe
found that ideational apraxia was present in both groups and, damage and no deficits were present in the other two groups
although less common, could occur in the absence of IMA (Halsband, 2001). The preservation of gesture recognition in
(Kertesz et al., 2000). CBD implies frontal rather than parietal or temporal lobe
In patients with clinically diagnosed CBD, perhaps the most damage.
commonly recognized type of apraxia—and the one that has Limb-kinetic apraxia is one of the most striking features of
received the most attention—is ideomotor limb apraxia CBD, although it is not exclusive to this disorder (Leiguarda
1486 Brain (2005), 128, 1480–1497 C. Zadikoff and A. E. Lang

et al., 1997). It was first described by Kleist in 1907 as an 2003). These deficits are reminiscent of those considered
‘innervatory apraxia’ (Kleist, 1907), and then Liepmann typical of LKA. Perhaps, then, LKA is better classified as a
advanced the term ‘limb-kinetic apraxia’ (Liepmann, 1920). primary or elemental motor dysfunction, with variable pre-
He considered it the ‘most motor’ apraxia. Its existence as an sentation based on the extent of pathological changes, rather
actual apraxia, rather than a consequence of more elemental than a type of apraxia.
motor deficits, was largely ignored until its occurrence in CBD The features of apraxia, including buccofacial apraxia, were
was recognized (Geschwind, 1965; Heilman, 1985; Okuda evaluated in 10 patients with clinically diagnosed CBD
et al., 1992; Denes et al., 1998; Leiguarda et al., 2000a). (Leiguarda et al., 1994). Although seven patients had IMA
This has brought renewed interest in this type of apraxia. and three had both IMA and ideational apraxia, no patient
Unlike IMA, which is typically bilateral, LKA is usually uni- demonstrated buccofacial apraxia. In contrast to the lack of
lateral and involves the most affected limb. Ideomotor apraxia OFA in this study, others have found this to be a common
and LKA may be combined in the same limb. As outlined in feature in patients with CBD. Ozsancak et al. (2000) evaluated
Table 1, LKA consists of impaired, coarse, ‘mutilated’ execu- dysarthria and OFA in 10 patients with clinically diagnosed
tion of simple movements of the hand contralateral to the CBD: 9 patients had dysarthria, and voluntary movements of
cortical lesion. This is more evident distally than proximally the tongue and lips were impaired in all 10. Orofacial apraxia
and is most notable for incoordination between fingers, as for simple gestures was present in only four patients, whereas
seen in object manipulation tasks and fine finger movements. impairment of sequential gestures was present in nine
This makes it the most difficult praxis disorder to distinguish patients. A rare presentation for CBD is the combination
from bradykinesia, rigidity and dystonia—three movement of profound dysarthria and OFA (Lippa et al., 1991; Lang,
deficits commonly seen in CBD. Leiguarda et al. (2003) stud- 1992; Tanaka et al., 2001). One of our patients first noted
ied the clinical and kinematic features of LKA in five patients difficulties pronouncing words. He ultimately became anarth-
with clinically diagnosed CBD compared with five patients ric and exhibited apraxia of all facial movements at a time
with Parkinson’s disease and ten controls using a compre- when he had no other clinical deficits. Subsequent post-
hensive apraxic battery, three-dimensional motion analysis of mortem study demonstrated a predominance of cortical
manipulative movements and motor evoked potentials. They pathology in the region of Broca’s area in the dominant
found that all five CBD patients demonstrated a unilateral left hemisphere in contrast to the more typical mesial pre-
praxic deficit characterized by chaotic movement with dominance of cortical pathology in CBD (Bergeron et al.,
marked interfinger incoordination. Using a measure of move- 1996).
ment quality (QMC) they showed that the QMC was signi- Eye movement abnormalities that perhaps represent a type
ficantly different in the CBD patients compared with controls of oculomotor apraxia can be seen in CBD as well. Cogan first
and most notably patients with Parkinson’s disease, suggest- used the term ‘oculomotor apraxia’ to refer to ‘the inability to
ing that neurological abnormalities such as bradykinesia and initiate horizontal saccades in the head-fixed condition’. The
rigidity alone are not able to explain LKA. They hypothesized oculographic pattern is characterized by increased latencies
that dysfunction in the premotor cortex accounts for LKA. and decreased amplitude of horizontal saccades. In his series,
The results of a study to assess processes underlying apraxic vertical saccades were normal (Cogan, 1953; Cogan and
disorders in CBD, using a cognitive model based on work by Adams, 1953). Oculomotor apraxia is characteristic of two
Roy and Square (1985), also supported dysfunction of the diseases (both of which may demonstrate prominent move-
premotor cortex in LKA (Blondel et al., 1997). Finally, clini- ment disorders): ataxia telangiectasia and ataxia oculomotor
copathological evidence in five patients also supports the role apraxia. In the former, reflexive and voluntary saccade laten-
of damage to the premotor cortex underlying LKA in CBD cies are prolonged, saccades are hypometric, velocities are
(Tsuchiya et al., 1997). normal and head movements are used to initiate gaze shifts
There is some debate, however, as to whether ‘limb-kinetic (Stell et al., 1989; Lewis et al., 1999). This is quite typical of
apraxia’ is a misnomer as well. As mentioned previously, Cogan’s initial description. In ataxia oculomotor apraxia, on
initially Liepmann did refer to it as a true apraxia, yet others the other hand, latencies are said to be normal but saccades are
disagreed and felt it was a primary motor deficit. With its extremely hypometric (mimicking slow eye movements),
more recent recognition in CBD, it has generally been con- square wave jerks are present and synkinetic blinking is
sidered an apraxia again; however, there are reasons to ques- used to compensate for lack of vestibulo-ocular reflex can-
tion this classification. For example, damage to the pyramidal cellation. There is also a dissociation of eye–head movements
tracts in primates is recognized to result in clumsy movements in which the head reaches the target before the eyes (Le Ber
characterized by an isolated deficit in independent finger et al., 2003, 2004). Although not well recognized at first, eye
movements (Tower, 1940; Lawrence and Kuypers, 1968). Fur- movement abnormalities are a common manifestation of
thermore in amyotrophic lateral sclerosis, often ‘loss of frac- CBD with characteristics reminiscent of the original descrip-
tionated movement is an early characteristic of hand tion by Cogan. Horizontal and vertical eye movements are
dysfunction’ (Weber et al., 2000), typically long before the equally affected. Typically, the latency of saccades and not
occurrence of other cognitive disturbances that might suggest their velocity is impaired. Initiation of horizontal saccades
more widespread cortical involvement (Lomen-Hoerth et al., can be delayed and some patients are unable to produce
Apraxia in movement disorders Brain (2005), 128, 1480–1497 1487

voluntary horizontal saccades, but this improves when some- that examined six patients with clinically diagnosed CBD (all
thing is given to them to look at. Eye blinking and head of whom had limb apraxia), regional cortical oxygen meta-
movements may be used to initiate voluntary saccades (Rebeiz bolism was globally reduced, but more significantly so in the
et al., 1967; Gibb et al., 1989; Lang et al., 1994b). In support of superior prefrontal cortex, both lateral and mesial premotor
considering this a manifestation of apraxia, one study found a areas and in the sensorimotor, inferior parietal and superior
relationship between the apraxia score and the saccade latency temporal cortices (Sawle et al., 1991). Striatal 18F-6-
(Vidailhet and Rivaud-Péchoux, 2000). The characteristics of fluorodopa uptake was reduced in an asymmetric pattern
the eye movement abnormalities have been used to distin- as well, with the caudate and putamen being involved in
guish CBD from PSP, where vertical saccade impairment is an all cases. Using a voxel-based approach and 18flourodeoxy-
early feature, saccadic velocity (but not latency) is impaired, glucose (18FDG) positron emission tomography, another
the presence of square wave jerks is almost a uniform feature study found a similar metabolic profile when 22 patients
and more errors are found on an antisaccade task (Vidailhet with clinically diagnosed CBD were studied (Garraux et al.,
and Rivaud-Péchoux, 2000). In addition to characterizing 2000). Other positron emission tomography studies have
patients with the classical presentations of CBD or PSP, shown similar patterns of reductions in regional oxygen con-
these eye movement differences may also be useful in dis- sumption and glucose metabolism (Blin et al., 1992; Eidelberg
tinguishing patients with more atypical presentations. et al., 1991). The changes in regional cerebral blood flow have
Rivaud-Pechoux et al. (2000) followed a group of 16 patients also been studied using 99mTc-HMPAO SPECT (Frasson et al.,
(9 diagnosed with CBD and 7 with PSP), longitudinally with 1998; Markus et al., 1995; Morimatsu and Negoro, 1995).
electro-oculography and clinical exams 6 months apart, for a These studies also showed significant reductions of regional
mean of 37 months. They divided the CBD group into cerebral blood flow in the more affected hemisphere, with the
‘probable’ (six out of nine) and ‘atypical CBD’ (three out posterior frontal cortex, parietal lobe, caudate, thalamus and
of nine) because the latter group did not fit all diagnostic putamen being most commonly affected. Okuda et al. (1995)
criteria for CBD (Litvan et al., 1997). In the probable CBD used N-isopropyl-p[123I]-iodoamphetamine in two patients
group they found that horizontal saccades remained with CBD. Both had LKA and one had constructional apraxia.
impaired, characterized by increase in saccade latency of Both showed asymmetrical cortical hypoperfusion in the peri-
reflexive visually guided saccades over time, and this was rolandic area, supporting the importance of dysfunction of
more marked ipsilateral to the side in which apraxia predom- this area to LKA, and the patient with constructional apraxia
inated. Horizontal saccade velocity did not decrease and had unilateral hypoperfusion in the left posterior parietal area.
square wave jerks were infrequently present. However, in In an attempt to further refine our understanding of the
the atypical CBD group, early square wave jerks, decreased neural networks involved in IMA in CBD, attempts to cor-
saccade velocity and a high percentage of errors in the antisac- relate 18FDG positron emission tomography data with a cog-
cade test were more suggestive of PSP, and 4–6 months nitive neuropsychiatric assessment of apraxia have been
following the electro-oculography recordings, the early made. In one such study that evaluated 18 patients with
clinical diagnosis of CBD was revised to a diagnosis of PSP CBD, two complementary measures of apraxia were used.
(Rivaud-Pechoux et al., 2000) (Table 2). First, a performance score measured error frequency during
gesture execution and, second, a correction score measured
the patient’s ability to correct initial errors on a second
Imaging and electrophysiology in attempt. The authors found that anterior cingulate hypometa-
corticobasal degeneration and apraxia bolism predominated in patients with CBD who performed
Imaging studies have been used to support the diagnosis of below the cutoff performance score for apraxia (14/18) and
CBD. One of the most striking features, when clinical asym- that in those (7 out of 18) who could not correct their errors
metry is evident, is the asymmetry of frontoparietal cortical (which occurred mainly in gesture imitation), hypometabol-
atrophy on MRI and CT, which is most notable contralateral ism in the contralateral superior parietal lobe and supple-
to the most severely affected side. In one series this asymmetry mentary motor area predominated, although there was also
was an almost constant feature with mild signal changes seen a deficit noted in the ipsilateral precentral gyrus (Peigneux
in the atrophic cortex (mainly on fluid-attenuated inversion et al., 2001).
recovery and proton density sequences) but minimal or no Other techniques that have been used to examine the cent-
abnormalities evident in the basal ganglia (Savoiardo et al., ral mechanisms underlying limb apraxia in CBD include
2000). Early in the disease the asymmetric changes may be somatosensory evoked potentials and transcranial magnetic
subtle, and late in the course bilateral abnormalities may be stimulation. For example, somatosensory evoked potentials in
evident. Recently volumetric imaging has been used to try to five patients with CBD have been compared with those in 12
differentiate between CBD and other parkinsonian syndromes controls (Okuda et al., 1998). This study found that all
(Groschel et al., 2004), although none to our knowledge has patients with limb apraxia, particularly LKA, had prolonged
specifically studied apraxia. On the other hand, several func- N20 latencies following median nerve stimulation on the
tional imaging studies have attempted to evaluate the patho- more apraxic side, suggesting that somatosensory informa-
physiological mechanisms underlying apraxia. In one study tion processing involving the parietal cortex might be
1488 Brain (2005), 128, 1480–1497 C. Zadikoff and A. E. Lang

Table 2 Apraxia in CBD

No. of IMA LKA Ideational Orobuccal
subjects

Jacobs et al., 1999 6 CBD +, spatial and temporal NA NA NA

errors predominated
Pillon et al., 1995 15 +, inclusion criteria + 3/15 0 +
included presence of
apraxia
Blondel et al., 1997 3 + + NA NA
Okuda et al., 1992 2 NA 2 NA NA
Tsuchiya et al., 1997 5 NA 2 NA NA
Denes et al., 1998 5 3 +, inclusion criteria NA 1
included presence of LKA
Martinez-Lage et al., 1997 24 23 NA 23 NA
Ozsancak et al., 2000 10 NA NA NA 9 dysarthria, simple
gestures impaired in 5,
sequential gestures
impaired in 1
Leiguarda et al., 2003 5 5 5 1 NA
Leiguarda et al., 1994 10 7 NA 3 0
Frattali and Sonies 2000 13 NA NA NA 6 (46%) had oral apraxia
5 (38%) had oral apraxia
and apraxia of speech

CBD = corticobasal degeneration; IMA = ideomotor apraxia; LKA = limb-kintetic apraxia; NA = not available; + = present in all subjects.

involved. The problem with all these studies is not only that better examples of this is the experience reported from the
most of the cases assessed were clinically diagnosed, and not Mayo Clinic in which 47% of cases (16/34) diagnosed as CBD
autopsy confirmed, but also, and more importantly for the in life had non-CBD pathology at autopsy. Almost without
purposes of this discussion, that most patients studied had exception it is the occurrence of apraxia, especially if asym-
other deficits, including dystonia, rigidity and cortical sensory metrical, associated with an akinetic-rigid syndrome, that
loss. Furthermore, many of the functional imaging studies encourages this misdiagnosis (Boeve et al., 2003).
were done in the resting state, and not while undergoing
tests of praxis. Thus, it is impossible to be certain about
Progressive supranuclear palsy
the relationship between the metabolic or electrophysiological
findings and the presence of apraxia. Progressive supranuclear palsy deserves special mention as it
is one of the most common disorders that is confused with
CBD. In the absence of a vertical supranuclear palsy and early
falls suggestive of PSP and lateralized motor and cognitive
Apraxia in other movement disorders signs of CBD, clinical overlap including the presence of
Other diseases can also give rise to the clinical picture typically apraxia can pose a diagnostic dilemma (Litvan et al.,
ascribed to CBD, and so the approach to diagnosis is shifting 1999). One study examined IMA in 14 patients with possible
from a single disease entity, CBD, to considering a number of PSP using diagnostic criteria of Litvan et al. (1996) and 12
different diseases capable of exhibiting a similar clinical patients fulfilling modified criteria for CBD from Lang et al.
phenotype, the CBS. This is comparable to the use of the (1994b) to determine whether there were any distinguishing
term parkinsonism to describe a clinical syndrome and features between the two groups that might be useful clinically
Parkinson’s disease to refer to one distinct pathological (Pharr et al., 2001). Not surprisingly, the study found that the
cause of this syndrome. Several other pathological entities overall praxis performance was worse in patients with CBD
may present with the CBS including PSP (Boeve et al., than in those with PSP, although the latter also scored lower
1999; Saint-Hilaire et al., 1996), Alzheimer’s disease (Ball than controls. Transitive tasks were more affected in PSP than
et al., 1993; Eberhard et al., 1996; Riley, 1996), Pick’s disease intransitive tasks. In CBD, transitive tasks were also more
(Lang et al., 1994a; Fukui et al., 1996; Boeve et al., 1999), affected than intransitive tasks, although both were affected,
motoneuron inclusion disease with dementia (Grimes et al., and distal movements were more affected than proximal
1999), FTD-17 and Creutzfeldt–Jakob disease (Boeve et al., movements. The authors concluded that intransitive tasks
2003). These experiences suggest that it is the anatomical are the best apraxia measure to distinguish between PSP
distribution of the pathological changes, and not the exact and CBD. Interestingly, in the CBD group distal movements
nature of this pathology, that results in the clinical phenotype. were considered most affected, suggesting that at least some of
Increasingly, autopsy series of cases diagnosed as CBD in life the deficits in these patients could be accounted for by LKA in
are providing strong support for this concept. One of the addition to or instead of IMA.
Apraxia in movement disorders Brain (2005), 128, 1480–1497 1489

In a more recent study comparing only intransitive gestures dystonia and arm levitation) and to those with CBD, PSP
in 24 patients with CBD, 25 with PSP and 19 controls, total patients with atypical signs had more severe cortical degen-
apraxia scores were worse in both disease groups compared eration than classic PSP patients but less cortical pathology
with controls but CBD patients were consistently more com- than patients with CBD. The cortical changes for all three
promised than PSP patients in executing simple gestures. The patient groups were most severe in the frontal lobe (Bergeron
CBD cohort committed more awkwardness and spatial errors et al., 1997). This again supports the argument made earlier
than the PSP group, consistent with LKA, whereas sequencing that it is the location of the pathology and the degree of
errors were similar among the two groups (Soliveri et al., changes present, and not the nature of the pathological
2005). However, as emphasized previously, these two studies changes, that lead to the clinical features of the CBS.
suffer from lack of pathological proof of diagnosis and bias
inherent in the evaluation of a clinical feature that is an
important diagnostic criterion of one disorder (i.e. CBD) Idiopathic Parkinson’s disease
and often a source of diagnostic doubt or even an exclusionary Apraxia has also been described in idiopathic Parkinson’s
criterion for the other (i.e. PSP). disease. In the report by Leiguarda et al., 1997 discussed
In another study comparing the presence of apraxia in 45 above, bilateral IMA for transitive movements was found
non-demented Parkinson’s disease patients, 12 with PSP, 10 in 27% (12) of the patients with Parkinson’s disease versus
with MSA and 12 patients with neuroleptic-induced parkin- 75% of patients with PSP. The scores in the levodopa respons-
sonian, bilateral IMA for transitive movements was present in ive patients did not differ between the ON and OFF states. The
8 (75%) of the PSP cases, and 5 of these also had abnormalities most common error type was spatial organization. None of
in intransitive movements (Leiguarda et al., 1997). None the Parkinson’s disease patients exhibited IMA for intransitive
showed errors of recognition of pantomimes and the total tasks, had errors of recognition of pantomimes or had oro-
apraxia scores correlated with cognitive disturbances, most facial or respiratory apraxia. As in the PSP group, apraxia
notably frontal lobe dysfunction. Of note, the authors scores in patients with Parkinson’s disease correlated with
described five patients who showed ‘very awkward and clumsy cognitive disturbances, namely frontal lobe dysfunction,
movements preceded by hesitation and unsuccessful attempts again emphasizing the importance of corticostriatal connec-
when pantomiming any movement, irrespective of the type of tions in the generation of IMA. Importantly, there was no
the gesture and the modality for evoking them’. They stated correlation between apraxia scores and motor disability, as
that these difficulties were more than one could expect based measured by the Unified Parkinson’s Disease Rating Scale,
on the severity of rigidity and/or bradykinesia and they were reemphasizing the point that limb apraxia can be examined in
more obvious in the most affected hand. This description is the presence of, and is not explained by, classical parkinsonian
very suggestive of LKA. The authors also assessed patients for motor disability.
features of orofacial and respiratory apraxia. Of the PSP A few other studies have also examined praxis in idiopathic
patients, 10 demonstrated OFA and 8 had respiratory apraxia. Parkinson’s disease. One study compared the performance of
The most striking feature noted was that of an overall final 15 Parkinson’s disease patients with controls on two tasks: (i)
correct performance preceded by long pauses during which a symbolic representation of implement usage on verbal com-
unsuccessful attempts were made. The authors commented, mand and on imitation and (ii) an imitation of non-symbolic
however, that it was sometimes difficult to interpret the hand positions (Sharpe et al., 1983). The patients with
nature of errors in the presence of the typical dystonic facial Parkinson’s disease performed at a lower gestural level on the
appearance of PSP. representational task and made more spatial errors on the
In a case report of a patient who fitted the clinical descrip- non-representational task. Another study evaluated imitation
tion of PSP except that he had ‘moderate to severe apraxia’, of movement sequences in 42 patients with moderate to severe
a postmortem demonstrated pathology consistent with PSP Parkinson’s disease compared with controls (Goldenberg
but also senile plaques and tangles in the frontoparietal areas et al., 1986). Again, the patients with Parkinson’s disease
suggestive of early Alzheimer’s disease (Pharr et al., 1999). The had worse total apraxia scores, and these scores correlated
authors suggested that when a patient with presumed PSP with visuospatial disability but not with motor severity. Not
demonstrates moderate to severe apraxia, the diagnosis of PSP surprisingly, Villardita et al. (1982) found that visuopercept-
must be questioned. However, although brainstem and basal ive disabilities were responsible for ‘constructional apraxia’ in
ganglia pathology was initially emphasized in PSP, it has a group of 20 patients with Parkinson’s disease. This disorder
become increasingly clear that cortical involvement is a fea- is distinct from the forms of motor apraxia that are the main
ture of the disorder. In a series of 10 cases of definite PSP, subject of this review. Finally, a series evaluating motor praxis
cortical lesions were a constant feature and the density of (gestural functioning) in 22 non-demented patients with
neurofibrillary tangles was highest in the precentral and angu- relatively mild Parkinson’s disease (27% Hoehn & Yahr
lar gyri (Verny et al., 1996). These cortical lesions may play a stage 1; 69% Hoehn & Yahr stage 2) found that 63% of
significant role in the clinical phenomenology. In a clinical- these patients differed from controls in praxis performance
pathological study comparing PSP patients with classic pre- (Grossman et al., 1991). The majority of errors involved sub-
sentation to those with unusual signs (i.e. limb apraxia, focal stitution of body part for object. Although responses were
1490 Brain (2005), 128, 1480–1497 C. Zadikoff and A. E. Lang

slow, as might be expected as a result of bradykinesia, the later in the course of the illness may be helpful in distinguish-
degree of gestural impairment did not correlate with degree of ing Alzheimer’s disease from DLB. Ideomotor apraxia, on the
motor disability. Finally, neuropsychological screening was other hand, has been found in up to one-third of patients with
performed in this study but did not include specific tests mild dementia of the Alzheimer’s type (Della et al., 1987;
of perseveration and frontal lobe functions. Taylor, 1994; Derouesne et al., 2000). Although, to our know-
ledge, this feature, has not been assessed in DLB, the 27%
incidence in Parkinson’s disease found by Leiguarda et al.
Dementia with Lewy bodies, Parkinson’s (1997), especially in those with cognitive dysfunction,
disease dementia or Alzheimer’s disease might predict a similar or greater incidence in DLB. This
Dementia with Lewy bodies is another parkinsonian disorder suggests that the presence of this type of apraxia early in
that may manifest apraxia. Distinguishing between diseases the course of a dementing illness may not be a very useful
that manifest the combination of parkinsonism and cognitive distinguishing feature.
decline (such as DLB and Alzheimer’s disease) can sometimes
be difficult, especially because it is widely recognized that
Alzheimer’s disease pathology (senile plaques and neurofib- Multiple system atrophy
rillary tangles) often coexists with Lewy bodies (Crystal et al., Relatively little has been published on the presence of apraxia
1993; Lippa et al., 1994; McKeith et al., 1996). Some suggest in MSA. No studies have examined apraxia in MSA separately,
that the timing of apraxia in relation to the disease onset and but rather this group of patients is usually studied in com-
coexistence with other features (e.g. hallucinations, fluctu- parison with other parkinsonian syndromes. In the study by
ations in level of awareness) may actually be of diagnostic Leiguarda et al. (1997), none of the patients with MSA (n =
value. In a series evaluating the effect of coexisting Alzheimer- 10) or neuroleptic-induced parkinsonian demonstrated any
type lesion load, clinical and pathological features were praxic errors. In another study by the same group, three-
assessed in two groups of patients with DLB (del Ser et al., dimensional computer graphic analysis was used to study
2001). The authors studied 35 Alzheimer’s disease, 11 pure the repetitive gesture of slicing bread. None of the four
DLB and 18 Alzheimer’s disease plus DLB pathologically patients with MSA had apraxia clinically, but on three-
confirmed cases. Not surprisingly, the most useful criteria dimensional analysis they did show deficits in control of
in distinguishing DLB from Alzheimer’s disease were similar the direction of the movement axis and in spatial patterns,
to the DLB consensus criteria, including hallucinations and albeit that these were much milder than in the patients with
cognitive fluctuations, especially when present early in the Parkinson’s disease and PSP (Leiguarda et al., 2000b). Finally,
disease course (McKeith et al., 1996). The Alzheimer’s disease in one series IMA was described in 2 of 19 patients with MSA,
and Alzheimer’s disease plus DLB patients in this series had although the majority of this group also showed evidence of
lower (worse) scores on the Extended Scale for Dementia. executive dysfunction (Monza et al., 1998). It is presumably
Ideational apraxia was less frequent in the pure DLB group the relative lack of frontal/cognitive impairment in MSA
(18%) compared with the groups with Alzheimer’s disease patients that spares the praxis system.
(54%) and Alzheimer’s disease plus DLB (27%).
In contrast to the higher prevalence of ideational apraxia in
Alzheimer’s disease, constructional apraxia, as tested by draw- Huntington’s disease
ing pentagons, has been found to be significantly worse in Ideomotor limb apraxia also occurs in Huntington’s disease.
patients with DLB (Cormack et al., 2004). Constructional In a small series of nine patients, 33% met criteria for IMA
apraxia indicates a drawing disturbance without general (Shelton and Knopman, 1991). The degree of apraxia correl-
impairment of intelligence, visual or motor capabilities and ated with the duration of Huntington’s disease and with over-
is usually caused by parietal lesions involving either hemi- all motor disability but not with cognitive dysfunction,
sphere. This study found that non-demented Parkinson’s dis- chorea, dystonia, rigidity or bradykinesia. The authors pos-
ease patients showed no abnormality of pentagon drawing but tulated that this was primarily due to basal ganglia dysfunc-
those with Parkinson’s disease dementia made errors com- tion because some of the patients who made errors had only
parable to the DLB group. This is not unexpected given the mild cognitive dysfunction [based on mini-mental state
current accepted continuum between Parkinson’s disease and examination scores and a 12-point auditory comprehension
DLB and the clinical and pathological similarities between test similar to the Token Test used for testing receptive apha-
Parkinson’s disease dementia and DLB (Burton et al., 2004; sia (De Renzi et al., 1982)], suggesting that cortical structures
McKeith and Mosimann, 2004). Although performance on were not yet involved; however, two of these patients had
this task correlated with global cognitive dysfunction in those mini-mental state examination scores of 21 and 22, respect-
with Alzheimer’s disease and Parkinson’s disease dementia, ively. Because of the small sample size and the fact that the
this was not the case in those with DLB, in whom drawing was most severely affected patients made the greatest apraxic
linked only to perception and praxis. Therefore, one might errors, a second group went on to study a larger set of patients
expect to find constructional apraxia earlier in the disease with a wider range of disease severity (Hamilton et al., 2003).
course in DLB, whereas the occurrence of ideational apraxia In 20 patients with Huntington’s disease, they also found a
Table 3 Studies of apraxia in movement disorders
Reference No. of patients Type of apraxia Types of errors Major differences between Observations
groups

PSP only
Nath et al., 2003 187 PSP ‘Eyelid apraxia’, present 32, No mention of other types
absent 52, not recorded 103 of apraxia
PSP and CBD
Pharr et al., 2001 13 CBD, 14 PSP PSP and CBD both had IMA. CBD patients made more CBD scores were worse
They both had more difficulty internal configuration errors overall and showed
with transitive than and more unclassifiable errors preferential worsening on
Apraxia in movement disorders

intransitive tasks than PSP, but otherwise tasks requiring distal upper
performance was similar extremity manoeuvring
across various error types
Monza et al., 2003 24 CBD, 25 PSP CBD patients had worse CBD patients had worse
total apraxia scores than PSP apraxia for whole upper limb
and hand/finger movements
Soliveri et al., 2005 24 CBD, 25 PSP, 19 72% CBD and 32% PSP Simple gesture performance CBD scores were worse
controls had total scores in the was worse in CBD group. overall. Errors in CBD
apraxia range Sequencing errors did not were thought to be
differ between the PSP and consistent with LKA
CBD group. CBD patients
made more awkwardness and
spatial errors than PSP group
PD
Sharpe et al., 1983 15 PD PD patients performed at Patients made more
lower gestural level on spatial errors on
representational tasks non-representational tasks
Goldenberg et al., 1986 42 PD IMA Errors were mainly in Degree of impairment
sequencing correlated with visuos-
patial and visuoperceptive
abilities
Grossman et al., 1991 22 PD patients 64% of PD patients had Most common errors were Patients were not
compromised gestural body substitution, and errors demented and scores
performance were made on representa- did not correlate with
tional more than non- motor deficit
representational gestures
Other parkinonsian disorders including PD and PSP
Leiguarda et al., 1997 45 PD, 12 PSP, IMA for transitive in 85% PSP Mainly spatial errors. IMA for intransitive Correlation between IMA
10 MSA, 12 NIP (8/12) and 27% PD (12/45). No problems with gesture gestures was found in in PD and deficits in frontal
Orobuccal apraxia was found recognition in any group 4 PSP, no PD lobe. In PSP IMA correl-
in 10 PSP patients. LKA was ated with MMSE
found in 5 PSP patients
Brain (2005), 128, 1480–1497
1491
 1492

Table 3 Continued
Reference No. of patients Type of apraxia Types of errors Major differences between groups Observations
Brain (2005), 128, 1480–1497

Monza et al., 1998 19 MSA, 19 PSP, All groups made some errors After errors owing to PSP had more variable All subjects recognized
14 PD suggestive of IMA with PSP clumsiness, sequencing errors errors, i.e. sequencing gestures
being the most affected. 2/19 were the most common (50%), clumsiness (30%),
MSA. 3/15 PSP had De Renzi location (10%) and
scores of praxis significance orientation (10%),
whereas MSA were due
to clumsiness (85%)
and sequencing (15%)
HD
Hamilton et al., 2003 20 HD 7/20 (35%) with IMA Gestural impairment Apraxia correlated with
more evident for transitive duration illness and QNE
than intransitive (motor impairment),
especially eye movement
deficits but not with MMSE
Shelton and Knopman, 1991 9 HD patients 33% (3) patients exhibited Apraxia was present for Apraxia correlated with
IMA, 22% (2/9) made no transitive and intransitive duration of disease
apraxic errors and 26% had tasks but no errors were
some impairment of gestures made in recognition of
gestures

CBD = corticobasal degeneration; HD = Huntington’s disease; IMA = ideomotor apraxia; LKA = limb-kinetic apraxia; MMSE = mini-mental state examination; MSA = multiple system
atrophy; NIP = neuroleptic-induced parkinsonism; PD = Parkinson’s disease; PSP = progressive supranuclear palsy; QNE = quantified neurological examination.
C. Zadikoff and A. E. Lang
Apraxia in movement disorders Brain (2005), 128, 1480–1497 1493

35% frequency of apraxia. Again the apraxia scores did not

Huntington’s disease

CBD = corticobasal degeneration; DLB = dementia with Lewy bodies; IMA = ideomotor apraxia; MSA = multiple system atrophy; PDD = Parkinson’s disease dementia; PSP = progressive
correlate with chorea or cognitive status, but apraxic patients
did have more severe motor disability (namely, oculomotor
Not present
deficits) and longer disease duration. Although basal ganglia
Present neuronal loss might play a role in producing apraxia in
Huntington’s disease, it is important to acknowledge that

Rare
the more severely affected patients who demonstrate apraxia
also have greater evidence of cortical involvement. As pointed
out in the section discussing the role of the basal ganglia in
apraxia, it is more likely that interruption of corticostriatal
Not present

Not present

connections rather than pure basal ganglia dysfunction

underlies limb apraxia in Huntington’s disease.
Finally, although little has been written about OFA in
MSA

Rare

Huntington’s disease, this is probably a relatively common

feature. Bruyn and Went referred to it as ‘mimical apraxia’ in
which impairment in facio-labio-glosso-pharyngeal move-
probably correlates

ments is not explained by chorea or other elementary

studied. Presence

Present later in

motor disturbances. He described errors in performance of

with degree of

disease course
Not routinely
Not present

simple tasks such as protrusion of the tongue and putting the

dementia

tongue into the cheek, as well as in more complex tasks such as

coughing, winking and whistling. These errors were often
DLB

accompanied by limb apraxia as well (Bruyn and Went,

1986) (Tables 3 and 4).
movements

formally studied in PDD

not formally studied

Parkinson’s disease;
Parkinson’s disease

Conclusion
not affected; not

Not present in

Various types of apraxia have been described in patients with

uncomplicated
Not present

Uncommon;

movement disorders particularly those combining parkinson-

intransitive

ism and cognitive dysfunction. It is important to recognize

in PDD

that the presence of one type of apraxia does not exclude the
presence of other types and, in fact, multiple types can coexist
Table 4 Comparison of limb apraxia in selected movement disorders

in the same patient. At times, apraxia is a dominant feature

that contributes substantially to the patient’s disability, espe-
Common; transitive
affected more than

cially in the cases of ideational apraxia, in which everyday

object use is affected, and LKA, in which control over fine
Uncommon

Uncommon

finger movements is lost. On the other hand, motor disturb-

movements
intransitive

ances sufficient to constitute IMA may result in little or no

interference with function, particularly in the case of volun-
PSP

tary automatic dissociation, where task performance may

normalize when the patient is given the actual object to
use. It is unclear whether the presence of these motor dis-
movements affec-
Common; transitive

turbances supports a role of the basal ganglia in praxis. The

and intransitive

term ‘apraxia’ is also misapplied to some motor disturbances

that may be seen in movement disorder patients. Finally, it is
Common

unclear whether the motor dysfunction encompassed by the

Present

term ‘limb-kinetic apraxia’ is best considered a form of

CBD

ted

apraxia or a more ‘primary’ or ‘essential’ motor disturbance.

Further studies, including careful clinical assessment and ana-
lysis, functional imaging, kinematic evaluations and prospect-
supranuclear palsy.

ive clinical-pathological studies, are needed to clarify these

Ideational apraxia
LKA, distal hand,

issues and answer the many questions that arise in the evalu-
IMA, proximal
bilateral, but

ation of apraxia in movement disorder patients. Standardized

asymmetric
unilateral

methods of evaluating such patients are required, with an

effort to reach wider consensus on the quantification, char-
acterization and applied terminology. Only then will it be
1494 Brain (2005), 128, 1480–1497 C. Zadikoff and A. E. Lang

possible to begin to understand the role of the different neural Cogan DG, Adams RD. A type of paralysis of conjugate gaze (ocular motor
networks involved in producing these complex disorders of apraxia). Ama Arch Ophthalmol 1953; 50: 434–42.
Cormack F, Aarsland D, Ballard C, Tovee MJ. Pentagon drawing and neuro-
movement. psychological performance in Dementia with Lewy Bodies, Alzheimer’s
disease, Parkinson’s disease and Parkinson’s disease with dementia. Int J
Geriatr Psychiatry 2004; 19: 371–7.
Acknowledgements Crystal HA, Dickson DW, Sliwinski MJ, Lipton RB, Grober E, Marks-Nelson
The Morton and Gloria Shulman Movement Disorders H, et al. Pathological markers associated with normal aging and dementia
Center has been designated a Center of Excellence by the in the elderly. Ann Neurol 1993; 34: 566–73.
National Parkinson’s Foundation. C.Z. was funded by the Defazio G, Livrea P, Lamberti P, De Salvia R, Laddomada G, Giorelli M, et al.
Isolated so-called apraxia of eyelid opening: report of 10 cases and a review
Parkinson Society of Canada Boeringher-Inhgelheim of the literature. Eur Neurol 1998; 39: 204–10.
Clinical Fellowship. The authors would like to thank Della SS, Lucchelli F, Spinnler H. Ideomotor apraxia in patients with demen-
Christine Klein and Sandra Black for their helpful comments tia of Alzheimer type. J Neurol 1987; 234: 91–3.
in preparation of this manuscript. del Ser T, Hachinski V, Merskey H, Munoz DG. Clinical and pathologic
features of two groups of patients with dementia with Lewy bodies: effect
of coexisting Alzheimer-type lesion load. Alzheimer Dis Assoc Disord 2001;
References 15: 31–44.
Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally Denes G, Mantovan MC, Gallana A, Cappelletti JY. Limb-kinetic apraxia.
segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci Mov Disord 1998; 13: 468–76.
1986; 9: 357–81. De Renzi E. Apraxia. In: Boller F, Grafman J, editors. Handbook of neuro-
Aramideh M, Ongerboer de Visser BW, Koelman JH, Bour LJ, Devriese PP, psychology. Amsterdam: Elsevier; 1989. p. 245–63.
Speelman JD. Clinical and electromyographic features of levator palpebrae De Renzi E, Luchelli F. Ideational apraxia. Brain 1988; 111: 1173–85.
superioris muscle dysfunction in involuntary eyelid closure. Mov Disord De Renzi E, Motti F, Nichelli P. Imitating gestures. A quantitative approach to
1994; 9: 395–402. ideomotor apraxia. Arch Neurol 1980; 37: 6–10.
Armstrong DM. The supraspinal control of mammalian locomotion. J Physiol De Renzi E, Faglioni P, Sorgato P. Modality-specific and supramodal mech-
1988; 405: 1–37. anisms of apraxia. Brain 1982; 105: 301–12.
Ball JA, Lantos PL, Jackson M, Marsden CD, Scadding JW, Rossor MN. Alien Derouesne C, Lagha-Pierucci S, Thibault S, Baudouin-Madec V, Lacomblez L.
hand sign in association with Alzheimer’s histopathology. J Neurol Apraxic disturbances in patients with mild to moderate Alzheimer’s
Neurosurg Psychiatry 1993; 56: 1020–3. disease. Neuropsychologia 2000; 38: 1760–9.
Basso A, Luzzatti C, Spinnler H. Is ideomotor apraxia the outcome of damage Dickson D, Liu WK, Yen SH. Neuropathologic and molecular consideratoins.
to well-defined regions of the left hemisphere? Neuropsychological study of In: Litvan, Goetz C, Lang AE, editors. Corticobasal degeneration and
CAT correlation. J Neurol Neurosurg Psychiatry 1980; 43: 118–26. related disorders. Philadelphia: Lippincott Williams & Wilkins; 2000.
Bergeron C, Pollanen MS, Weyer L, Black SE, Lang AE. Unusual clinical p. 9–29.
presentations of cortical-basal ganglionic degeneration. Ann Neurol Eberhard DA, Lopes MBS, Trugman JM, Brashear HR. Alzheimer’s disease in a
1996; 40: 72–9. case of cortical basal ganglionic degeneration with severe dementia.
Bergeron C, Weyer LPMS, Lang AE. Cortical degeneration in progressive J Neurol Neurosurg Psychiatry 1996; 60: 109–10.
supranuclear palsy. A comparison with cortical-basal ganglionic degenera- Eidelberg D, Dhawan V, Moeller JR, Sidtis JJ, Ginos JZ, Strother SC, et al.
tion. J Neuropathol Exp Neurol 1997; 56: 726–34. The metabolic landscape of cortico-basal ganglionic degeneration: regional
Blin J, Vidailhet M-J, Pillon B, Dubois B, Feve J-R, Agid Y. Corticobasal asymmetries studied with positron emission tomography. J Neurol
degeneration: decreased and asymmetrical glucose consumption as studied Neurosurg Psychiatry 1991; 54: 856–62.
with PET. Mov Disord 1992; 7: 348–54. Elble RJ, Cousins R, Leffler K, Hughes L. Gait initiation by patients with
Blondel A, Eustache F, Schaeffer S, Marie RM, Lechevalier B, de la lower-half parkinsonism. Brain 1996; 119: 1705–16.
Sayette V. [Clinical and cognitive study of apraxia in cortico-basal atrophy. Elston JS. A new variant of blepharospasm. J Neurol Neurosurg Psychiatry
A selective disorder of the production system]. Rev Neurol (Paris) 1997; 1992; 55: 369–71.
153: 737–47. Fahn S. Blepharospasm: a form of focal dystonia. In: Jankovic J, Tolosa E,
Boeve BF, Maraganore DM, Parisi JE, Ahlskog JE, Graff-Radford N, Caselli RJ, editors. Advances in neurology—facial dyskinesias. New York: Raven Press;
et al. Pathologic heterogeneity in clinically diagnosed corticobasal degen- 1988. p. 125–33.
eration. Neurology 1999; 53: 795–800. FitzGerald PM, Jankovic J. Lower body parkinsonism: evidence for vascular
Boeve BF, Lang AE, Litvan I. Corticobasal degeneration and its relationship to etiology. Mov Disord 1989; 4: 249–60.
progressive supranuclear palsy and frontotemporal dementia. Ann Neurol Frasson E, Moretto G, Beltramello A, Smania N, Pampanin M, Stegagno C,
2003; 54: S15–19. et al. Neuropsychological and neuroimaging correlates in corticobasal
Boghen D. Apraxia of lid opening: a review. Neurology 1997; 48: 1491–4. degeneration. Ital J Neurol Sci 1998; 19: 321–8.
Bruyn GW, Went LN. Huntington’s chorea. In: Vinken PJ, Bruyn GW, Frattali CM, Sonics BC. Speech and swallowing disturbances in coticobasal
Klawans HL, editors. Handbook of clinical neurology. Amsterdam: degeneration. Adv Neurol 2000; 82: 153–60.
Elsevier Science Publishers; 1986. p. 267–315. Freeman JS, Cody FW, Schady W. The influence of external timing cues upon
Burton EJ, McKeith IG, Burn DJ, Williams ED, OBrien JT. Cerebral atrophy the rhythm of voluntary movements in Parkinson’s disease. J Neurol
in Parkinson’s disease with and without dementia: a comparison with Neurosurg Psychiatry 1993; 56: 1078–84.
Alzheimer’s disease, dementia with Lewy bodies and controls. Brain Fukui T, Sugita K, Kawamura M, Shiota J, Nakano I. Primary progressive
2004; 127: 791–800. apraxia in Pick’s disease: a clinicopathologic study. Neurology 1996; 47:
Catalan MJ, Honda M, Weeks RA, Cohen LG, Hallett M. The functional 467–73.
neuroanatomy of simple and complex sequential finger movements: a Garraux G, Salmon E, Peigneux P, Kreisler A, Degueldre C, Lemaire C, et al.
PET study. Brain 1998; 121: 253–64. Voxel-based distribution of metabolic impairment in corticobasal degen-
Chang CM, Yu YL, Ng HK, Leung SY, Fong KY. Vascular pseudoparkinson- eration. Mov Disord 2000; 15: 894–904.
ism. Acta Neurol Scand 1992; 86: 588–92. Georgiou N, Iansek R, Bradshaw JL, Phillips JG, Mattingley JB, Bradshaw JA.
Cogan DG. A type of congenital ocular motor apraxia presenting jerky head An evaluation of the role of internal cues in the pathogenesis of parkin-
movements. Am J Ophthalmol 1953; 36: 433–41. sonian hypokinesia. Brain 1993; 116(Pt 6): 1575–87.
Apraxia in movement disorders Brain (2005), 128, 1480–1497 1495

Georgopoulos AP, DeLong MR, Crutcher MD. Relations between parameters Jueptner M, Weiller C. A review of differences between basal ganglia and
of step-tracking movements and single cell discharge in the globus pallidus cerebellar control of movements as revealed by functional imaging studies.
and subthalamic nucleus of the behaving monkey. J Neurosci 1983; Brain 1998; 121(Pt 8): 1437–49.
3: 1586–98. Kendall AL, David F, Rayment G, Torres EM, Annett LE, Dunnett SB. The
Geschwind N. Disconnexion syndromes in animals and man. II. Brain 1965; influence of excitotoxic basal ganglia lesions on motor performance in the
88: 585–644. common marmoset. Brain 2000; 123(Pt 7): 1442–58.
Geschwind N. The apraxias: neural mechanisms of disorders of learned Kertesz A, Martinez-Lage P, Davidson W, Munoz DG. The corticobasal
movement. Am Sci 1975; 63: 188–95. degeneration syndrome overlaps progressive aphasia and frontotemporal
Geschwind N, Kaplan E. A human cerebral deconnection syndrome. dementia. Neurology 2000; 55: 1368–75.
A preliminary report. Neurology 1962; 12: 675–85. Kleist K. Apraxie. Jarbuch Psychiatr Neurol 1907; 28: 46–112.
Geschwind N, Damasio AR. Apraxia. In: Vinken PJ, Bruyn G, Klawans HL, Krack P, Marion MH. ‘Apraxia of lid opening’, a focal eyelid dystonia: clinical
editors. Handbook of clinical neurology. Amsterdam: Elsevier; 1985. study of 32 patients. Mov Disord 1994; 9: 610–5.
p. 423–32. Krack P, Batir A, Van Blercom N, Chabardes S, Fraix V, Ardouin C, et al. Five-
Gibb WRG, Luthert PJ, Marsden CD. Corticobasal degeneration. Brain 1989; year follow-up of bilateral stimulation of the subthalamic nucleus in
112: 1171–92. advanced Parkinson’s disease. N Engl J Med 2003; 349: 1925–34.
Gibb WRG, Luthbert PJ, Marsden CD. Clinical and pathological features of Lamberti P, De Mari M, Zenzola A, Aniello MS, Defazio G. Frequency of
corticobasal degeneration. Adv Neurol 1990; 53: 51–4. apraxia of eyelid opening in the general population and in patients with
Goldenberg G, Wimmer A, Auff E, Schnaberth G. Impairment of motor extrapyramidal disorders. Neurol Sci 2002; 23(Suppl. 2): S81–2.
planning in patients with Parkinson’s disease: evidence from ideomotor Lang AE. Cortical-basal ganglionic degeneration presenting with ‘progressive
apraxia testing. J Neurol Neurosurg Psychiatry 1986; 49: 1266–72. loss of speech output and orofacial dyspraxia’. J Neurol Neurosurg
Goldstein JE, Cogan DG. Apraxia of lid opening. Arch Ophthalmol 1965; 73: Psychiatry 1992; 55: 1101.
155–9. Lang AE. Corticobasal degeneration: selected developments. Mov Disord
Graff-Radford NR, Welsh K, Godersky J. Callosal apraxia. Neurology 1987; 2003; 18: S51–6.
37: 100–5. Lang AE, Bergeron C, Pollanen MS, Ashby P. Parietal Pick’s disease mim-
Grafton ST, Hazeltine E, Ivry R. Functional mapping of sequence learning in icking cortical-basal ganglionic degeneration. Neurology 1994a; 44:
normal humans. J Cogn Neurosci 1995; 7: 497–510. 1436–40.
Grillner S, Deliagina T, Ekeberg O, el Manira A, Hill RH, Lansner A, et al. Lang AE, Riley DE, Bergeron C. Cortical-basal ganglionic degeneration. In:
Neural networks that co-ordinate locomotion and body orientation in Calne DB, editor. Neurodegenerative diseases. Philadelphia: W.B.Saunders;
lamprey. Trends Neurosci 1995; 18: 270–9. 1994b. p. 877–94.
Grimes DA, Lang AE, Bergeron C. Dementia is the most common pre- Lawrence DG, Kuypers HG. The functional organization of the motor system
sentation of cortical-basal ganglionic degeneration. Neurology 1998; in the monkey. I. The effects of bilateral pyramidal lesions. Brain 1968; 91:
50(Suppl 4): A96. 1–14.
Grimes DA, Bergeron CB, Lang AE. Motor neuron disease-inclusion demen- Le Ber I, Moreira MC, Rivaud-Péchoux S, Chamayou C, Ochsner F,
tia presenting as cortical-basal ganglionic degeneration. Mov Disord 1999; Kuntzer T, et al. Cerebellar ataxia with oculomotor apraxia type 1: clinical
14: 674–80. and genetic studies. Brain 2003; 126: 2761–72.
Groschel K, Hauser TK, Luft A, Patronas N, Dichgans J, Litvam I, et al. Le Ber, I, Bouslam N, Rivaud-Pechoux S, Guimaraes J, Benomar A,
Magnetic resonance imaging-based volumetry differentiates progressive Chamayou C, et al. Frequency and phenotypic spectrum of ataxia with
supranuclear palsy from corticobasal degeneration. Neuroimage 2004; oculomotor apraxia 2: a clinical and genetic study in 18 patients. Brain
21: 714–24. 2004; 127: 759–67.
Grossman M, Carvell S, Gollomp S, Stern MB, Vernon G, Hurtig HI. Sentence Leiguarda RC, Marsden CD. Limb apraxias—higher-order disorders of
comprehension and praxis deficits in Parkinson’s disease. Neurology 1991; sensorimotor integration. Brain 2000; 123: 860–79.
41: 1620–6. Leiguarda R, Lees AJ, Merello M, Starkstein S, Marsden CD. The nature of
Halsband U, Schmitt J, Weyers M, Binkofski F, Grutzner G, Freund HJ. apraxia in corticobasal degeneration. J Neurol Neurosurg Psychiatry 1994;
Recognition and imitation of pantomimed motor acts after unilateral 57: 455–9.
parietal and premotor lesions: a perspective on apraxia. Neuropsychologia Leiguarda RC, Pramstaller PP, Merello M, Starkstein S, Lees AJ, Marsden CD.
2001; 39: 200–16. Apraxia in Parkinson’s disease, progressive supranuclear palsy, multiple
Hamilton JM, Haaland KY, Adair JC, Brandt J. Ideomotor limb apraxia system atrophy and neuroleptic-induced parkinsonism. Brain 1997; 120:
in Huntington’s disease: implications for corticostriate involvement. 75–90.
Neuropsychologia 2003; 41: 614–21. Leiguarda R, Merello M, Balej J. Apraxia in corticobasal degeneration. Adv
Heilman KM. Apraxia. In: Heilman KM, Valenstein E, editors. Apraxia. New Neurol 2000a; 82: 103–21.
York: Oxford University Press; 1985. p. 131–50. Leiguarda R, Merello M, Balej J, Starkstein S, Nogues M, Marsden CD.
Heilman KM, Rothi LJ, Valenstein E. Two forms of ideomotor apraxia. Disruption of spatial organization and interjoint coordination in
Neurology 1982; 32: 342–6. Parkinson’s disease, progressive supranuclear palsy, and multiple system
Heilman KM, Maher LM, Greenwald ML, Rothi LJ. Conceptual apraxia from atrophy. Mov Disord 2000b; 15: 627–40.
lateralized lesions. Neurology 1997; 49: 457–64. Leiguarda RC, Merello M, Nouzeilles MI, Balej J, Rivero A, Nogués M.
Hennerici MG, Oster M, Cohen S, Schwartz A, Motsch L, Daffertshofer M. Limb-kinetic apraxia in corticobasal degeneration: clinical and kinematic
Are gait disturbances and white matter degeneration early indicators of features. Mov Disord 2003; 18: 49–59.
vascular dementia? Dementia 1994; 5: 197–202. Lepore FE, Duvoisin RC. ‘Apraxia’ of eyelid opening: an involuntary levator
Jacobs DH, Adair JC, Macauley B, Gold M, Gonzalez Rothi LJ, Heilman KM. inhibition. Neurology 1985; 35: 423–7.
Apraxia in corticobasal degeneration. Brain Cogn 1999; 40: 336–54. Lewis RF, Lederman HM, Crawford TO. Ocular motor abnormalities in ataxia
Jankovic J. Pretarsal injection of botulinum toxin for blepharospasm telangiectasia. Ann Neurol 1999; 46: 287–95.
and apraxia of eyelid opening. J Neurol Neurosurg Psychiatry 1996; 60: 704. Liepmann H. Drei Aufsatz aus dem Apraxiegebiet. Berlin: Karger; 1908.
Jankovic J, Friedman DI, Pirozzolo FJ, McCrary JA. Progressive supra- Liepmann H. Apraxie. Erebn ges Med 1920; 1: 516–43.
nuclear palsy: motor, neurobehavioral, and neuro-ophthalmic findings. Lippa CF, Cohen R, Smith TW, Drachman DA. Primary progressive aphasia
In: Streifler MB, Korczyn AD, Melamed E, Youdim MBH, editors. with focal neuronal achromasia. Neurology 1991; 41: 882–6.
Parkinson’s disease: anatomy, pathology, and therapy. New York: Raven Lippa CF, Smith TW, Swearer JM. Alzheimer’s disease and lewy body disease:
Press; 1990. p. 293–304. a comparative clinicopathological Study. Ann Neurol 1994; 35: 81–8.
1496 Brain (2005), 128, 1480–1497 C. Zadikoff and A. E. Lang

Liston R, Mickelborough J, Bene J, Tallis R. A new classification of higher level Peigneux P, Salmon E, Garraux G, Laureys S, Willems S, Dujardin K, et al.
gait disorders in patients with cerebral multi-infarct states. Age Ageing Neural and cognitive bases of upper limb apraxia in corticobasal degen-
2003; 32: 252–8. eration. Neurology 2001; 57: 1259–68.
Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, et al. Clinical Peigneux P, Van der Linden M, Garraux G, Laureys S, Degueldre C,
research criteria for the diagnosis of progressive supranuclear palsy Aerts J, et al. Imaging a cognitive model of apraxia: the neural
(Steele-Richardson-Olszewski syndrome): Report of the NINDS–SPSP substrate of gesture-specific cognitive processes. Hum Brain Mapp 2004;
International Workshop. Neurology 1996; 47: 1–9. 21: 119–42.
Litvan I, Agid Y, Goetz C, Jankovic J, Wenning GK, Brandel JP, et al. Accuracy Pharr V, Litvan I, Brat DJ, Troncoso J, Reich SG, Stark M. Ideomotor apraxia
of the clinical diagnosis of corticobasal degeneration: a clinicopathologic in progressive supranuclear palsy: a case study. Mov Disord 1999; 14:
study. Neurology 1997; 48: 119–25. 162–6.
Litvan I, Grimes DA, Lang AE, Jankovic J, McKee A, Vermy M et al. Pharr V, Uttl B, Stark M, Litvan I, Fantie B, Grafman J. Comparison of
Clinical features differentiating patients with postmortem confirmed pro- apraxia in corticobasal degeneration and progressive supranuclear palsy.
gressive supranuclear palsy and corticobasal degeneration. J. Neurol 1999; Neurology 2001; 56: 957–63.
246 (Suppl. 2): II1–5. Pillon B, Gouider-Khouja N, Deweer B, Vidailhet M, Malaoani C, Dubois B,
Litvan I, Bhatia KP, Burn DJ, Goetz CG, Lang AE, McKeith I, et al. SIC task et al. Neuropsychological pattern of striatonigral degeneration: comparison
force appraisal of clinical diagnostic criteria for parkinsonian disorders. with Parkinson’s disease and progressive supranuclear palsy. J Neurol
Mov Disord 2003; 18: 467–86. Neurosurg Psychiatry 1995; 58: 174–9.
Lomen-Hoerth C, Murphy J, Langmore S, Kramer JH, Olney RK, Miller B. Poizner H, Mack L, Verfaellie M, Rothi LJ, Heilman KM. Three-dimensional
Are amyotrophic lateral sclerosis patients cognitively normal? Neurology computergraphic analysis of apraxia. Neural representations of learned
2003; 60: 1094–7. movement. Brain 1990; 113(Pt 1): 85–101.
McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hensen LA, et al. Poizner H, Clark MA, Merians AS, Macauley B, Gonzalez Rothi LJ,
Consensus guidelines for the clinical and pathologic diagnosis of dementia Heilman KM. Joint coordination deficits in limb apraxia. Brain 1995;
with Lewy bodies (DLB): Report of the consortium on DLB international 118(Pt 1): 227–42.
workshop. Neurology 1996; 47: 1113–24. Pramstaller PP, Marsden CD. The basal ganglia and apraxia. Brain 1996;
McKeith IG, Mosimann UP. Dementia with Lewy bodies and Parkinson’s 119: 319–40.
disease. Parkinsonism Relat Disord 2004; 10(Suppl. 1): S15–8. Rebeiz JJ, Kolodny EH, Richardson EP. Corticodentatonigral degeneration
Markus HS, Lees AJ, Lennox G, Marsden CD, Costa DC. Patterns of regional with neuronal achromasia: a progressive disorder in late adult life. Trans
cerebral blood flow in corticobasal degeneration studied using HMPAO Am Neurol Assoc 1967; 92: 23–6.
SPECT: comparison with Parkinson’s disease and normal controls. Mov Riley DE. Alzheimer’s disease with a clinical presentation mimicking cortical-
Disord 1995; 10: 179–87. basal ganglionic degeneration. Mov Disord 1996; 11: 357.
Martin A, Haxby JV, Lalonde FM, Wiggs CL, Ungerleider LG. Discrete Rivaud-Pechoux S, Vidailhet M, Gallouedec G, Litvan I, Gaymard B, Pierrot-
cortical regions associated with knowledge of color and knowledge of Deseilligny C. Longitudinal ocular motor study in corticobasal degenera-
action. Science 1995; 270: 102–5. tion and progressive supranuclear palsy. Neurology 2000; 54: 1029–32.
Mink JW. The basal ganglia: focused selection and inhibition of competing Rothi LJ, Ochipa C. A cognitive neuropsychological model of limb praxis.
motor programs. Prog Neurobiol 1996; 50: 381–425. Cognit Neuropsychol 1991; 8: 443–58.
Mitchell SJ, Richardson RT, Baker FH, DeLong MR. The primate globus Rothi LJ, Heilman KM, Watson RT. Pantomime comprehension and
pallidus: neuronal activity related to direction of movement. Exp Brain ideomotor apraxia. J Neurol Neurosurg Psychiatry 1985; 48: 207–10.
Res 1987; 68: 491–505. Rothi LJ, Mack L, Verfaellie M, Brown P, Heilman KM. Ideomotor apraxia:
Monza D, Soliveri P, Radice D, Fetoni V, Testa D, Caffarra P, et al. Cognitive error pattern analysis. Aphasiology 1988; 2: 381–8.
dysfunction and impaired organization of complex motility in degenerative Roy EA, Square PA. Common considerations in the study of limb, verbal, and
parkinsonian syndromes. Arch Neurol 1998; 55: 372–8. oral apraxia. In: Roy EA, editor. Neuropsychological studies of apraxia and
Morimatsu M, Negoro K. [Corticobasal degeneration: symptomatological, related disorders. Amsterdam: North-Holland; 1985. p. 111–61.
brain-imaging and electrophysiological studies]. Rinsho Shinkeigaku 1995; Saint-Hilaire MH, Handler J, McKee AC, Feldman RG. Clinical overlap
35: 1459–62. between corticobasal ganglionic degeneration and progressive supranuclear
Monza D, Ciano C, Scailoi V, Soliveri P, Carella F, Avanzini G, Girotti F. palsy. Mov Disord 1996; 11(3): 356.
Neurophysiological features in relation to clinical signs in clinically dia- Savoiardo M, Grisoli M, Girotti F. Magnetic resonance imaging in CBD,
gnosed corticobasal degeneration. Neurol Sci 2003; 24: 16–23. related atypical parkinsonian disorders, and dementias. Adv Neurol
Nath U, Ben-Sholomo Y, Thomos KG, Lees AJ. Clinical features and natural 2000; 82: 197–208.
history of progressive supranuclear palsy: a clinical cohort study. Neuro- Sawle GV, Brooks DJ, Marsden CD, Frackowiak RS. Corticobasal degenera-
logy 2003; 60: 910–6. tion. A unique pattern of regional cortical oxygen hypometabolism
Nutt JG, Marsden CD, Thompson PD. Human walking and higher-level gait and striatal fluorodopa uptake demonstrated by positron emission
disorders, particularly in the elderly. Neurology 1993; 43: 268–79. tomography. Brain 1991; 114: 541–56.
Ochipa C, Rothi LJ, Heilman KM. Conceptual apraxia in Alzheimer’s disease. Schiller F. Staggering gait in medical history. Ann Neurol 1995; 37: 127–35.
Brain 1992; 115(Pt 4): 1061–71. Sharpe MH, Cermak SA, Sax DS. Motor planning in Parkinson patients.
Okuda B, Tachibana H, Kawabata K, Takeda M, Sugita M. Slowly progressive Neuropsychologia 1983; 21: 455–62.
limb-kinetic apraxia with a decrease in unilateral cerebral blood flow. Acta Shelton PA, Knopman DS. Ideomotor apraxia in Huntington’s disease. Arch
Neurol Scand 1992; 86: 76–81. Neurol 1991; 48: 35–41.
Okuda B, Tachibana H, Takeda M, Kawabata K, Sugita M, Fukuchi M. Focal Shik ML, Orlovsky GN. Neurophysiology of locomotor automatism. Physiol
cortical hypoperfusion in corticobasal degeneration demonstrated by Rev 1976; 56: 465–501.
three-dimensional surface display with 123I-IMP: a possible cause of Soliveri P, Piacentini S, Girotti F. Limb apraxia in corticobasal degeneration
apraxia. Neuroradiology 1995; 37: 642–4. and progressive supranuclear palsy. Neurology 2005; 64: 448–53.
Okuda B, Tachibana H, Takeda M, Kawabata K, Sugita M. Asymmetric Steinmetz H, Rademacher J, Huang YX, Hefter H, Zilles K, Thron A, et al.
changes in somatosensory evoken potentials correlate with limb Cerebral asymmetry: MR planimetry of the human planum temporale.
apraxia in corticobasal degeneration. Acta Neurol Scand 1998; 97: J Comput Assist Tomogr 1989; 13: 996–1005.
409–12. Stell R, Bronstein AM, Plant GT, Harding AE. Ataxia telangiectasia: a
Ozsancak C, Auzou P, Hannequin D. Dysarthria and orofacial apraxia in reappraisal of the ocular motor features and their value in the diagnosis
corticobasal degeneration. Mov Disord 2000; 15: 905–10. of atypical cases. Mov Disord 1989; 4: 320–9.
Apraxia in movement disorders Brain (2005), 128, 1480–1497 1497

Tanaka R, Kobayashi T, Takanashi M, Tadokoro H, Mori H, Suda K. et al. Verny M, Duyckaerts C, Agid Y, Hauw JJ. The significance of cortical
[A 68-year-old man with speech disturbance as the initial symptom fol- pathology in progressive supranuclear palsy—clinico-pathological data
lowed by bradykinesia and dementia. Clinical conference]. No To Shinkei in 10 cases. Brain 1996; 119: 1123–36.
2001: 53: 585–97. Vidailhet M, Rivaud-Péchoux S. Eye movement disorders in corticobasal
Taylor R. Motor apraxia in dementia. Percept Mot Skills 1994; 79: degeneration. Adv Neurol 2000; 82: 161–7.
523–8. Villardita C, Smirni P, le Pira F, Zappala G, Nicoletti F. Mental deterioration,
Thompson PD, Marsden CD. Gait disorder of subcortical arteriosclerotic visuoperceptive disabilities and constructional apraxia in Parkinson’s
encephalopathy: Binswanger’s disease. Mov Disord 1987; 2: 1–8. disease. Acta Neurol Scand 1982; 66: 112–20.
Tower S. Pyramidal lesion in the monkey. Brain 1940; 63: 36–90. Weber M, Eisen A, Stewart H, Hirota N. The split hand in ALS has a cortical
Tsuchiya K, Ikeda K, Uchihara T, Oda T, Shimada H. Distribution of cerebral basis. J Neurol Sci 2000; 180: 66–70.
cortical lesions in corticobasal degeneration: a clinicopathological study Wenger KK, Musch KL, Mink JW. Impaired reaching and grasping after focal
of five autopsy cases in Japan. Acta Neuropathol (Berl) 1997; 94: inactivation of globus pallidus pars interna in the monkey. J Neurophysiol
416–24. 1999; 82: 2049–60.