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: lang@uhnres.utoronto.ca
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 compromise
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
common the inability to perform a skilled or learned act
that cannot be explained by an elementary motor or sensory
deficit or language comprehension disorder. Praxis errors
have been well defined clinically and kinematically and can
be superimposed on elementary motor disorders such as
weakness, bradykinesia, rigidity, tremor, dystonia and ataxia
(Heilman, 1985; Roy and Square, 1985; Poizner et al., 1990,
1995). In many higher order apraxic disorders, such as
ideational apraxia, this does not usually pose a diagnostic
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dilemma. Although bradykinesia and other extrapyramidal
signs (e.g. rigidity or dystonia) might cause a delay in initiation
or performance of a gesture, the quality of the gesture
should not be affected by these and so gestural impairment
could not be explained by their presence alone. However, in
some cases, such as those with limb-kinetic apraxia (LKA),
bradykinesia and rigidity could readily compromise the ability
to distinguish the loss of dexterity and coarseness of movement
that characterize this subtype. In this review we will
begin with a summary of the basic types of apraxia and the
underlying neuroanatomical and physiological mechanisms
thought to play a role, particularly as they relate to diseases of
the basal ganglia. We will then discuss the different movement
disorder syndromes commonly, and not so commonly, associated
with apraxia. The neurological diseases chosen are
based largely on descriptions of apraxia in those conditions
in the literature as well as clinical experience. Certain disorders
that are called ‘apraxia’, such as eyelid opening apraxia
(ALO), but are probably better classified separately from
apraxia, are also addressed.
Overview of apraxia
The first contemporary ideas of apraxia stem from the work of
Liepmann, who proposed that in order to perform an action,
the motor engram (or ‘space–time plan’) has to be conveyed
from the left parietal lobe via association fibres to the ‘Central
region’, in which Liepmann included the precentral and postcentral
gyri, the middle and superior frontal gyri and their
underlying white matter tracts. The Central region effected
the action through the primary motor cortex, i.e. through the
final common pathway of the pyramidal tract. If the left limb
is to perform a task, then the information needed to be transmitted
through the corpus callosum to the Central region on
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 hemisphere
in praxis (Basso et al., 1980; De Renzi et al., 1980,
1982). Apraxia, as tested by imitation and object use pantomime,
has been found in 50% of patients with left hemisphere
damage and in <10% with right hemisphere damage.
This suggests that many patients have bilateral representation
of praxis functions (De Renzi, 1989). Even Liepmann pointed
out that the right hemisphere probably has some praxis skills,
and this has been used to explain why there is sparing of
certain left-hand praxis functions after callosal or left hemisphere
lesions (Geschwind and Kaplan, 1962; Graff-Radford
et al., 1987).
Damasio and Geschwind (1985) defined apraxia as demonstrating
varying combinations of the following disturbances
in order of progressive dysfunction: the failure to
produce the correct movement in response to a verbal command,
the failure to correctly imitate a movement performed
by the examiner, the failure to perform a movement correctly
in response to a seen object and the failure to handle an object
correctly. It is classified by both the nature of the errors made
and the means by which they are elicited. For instance, abnormal
performance can be due to ‘temporal errors’ (such as
impaired timing and poor sequencing of a movement that
requires multiple positionings, as long as the overall content
of the movement remains recognizable), ‘spatial errors’ (such
as abnormal amplitude, internal or external configuration
orientation and body-part-as-object substitution), ‘content
errors’ (such as perseveration) or ‘other errors’ (such as
lack of response or an entirely unrecognizable response)
(Rothi et al., 1988). Since Liepmann’s original description,
others have tried to advance his model in order to account for
different types of praxis errors. Roy and Square (1985) proposed
a two-part model in which a conceptual component
encodes an abstract knowledge base for actions, including
information about tool use and sequencing a series of single
actions, and a production component provides sensorimotor
information on how to perform an action ‘programme’ and
then translates these programmes into actions. Much of our
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
together. Depending on the neural network involved, the
types of errors will differ. For example, as pointed out by
Leiguarda and Marsden (2000), there is a parietofrontal system
that encodes reaching and grasping mechanisms, and a
frontostriatal system that encodes sequential motor events.
Moreover, the extent to which these systems are affected
depends on the context of the movement and the cognitive
demand of the action (Leiguarda and Marsden, 2000). Table
1, which summarizes the major classification of motor limb
apraxias (Rothi and Ochipa, 1991), will serve as a background
to the types of apraxia found in movement disorders
discussed below.
Role of the basal ganglia and apraxia
The motor and premotor areas of the cortex send projections
to the basal ganglia (Alexander et al., 1986), as do areas of the
parietal cortex that are interconnected with those areas of the
motor cortex, making up the parietofrontal circuits. These
circuits act in parallel. Each one is involved in sensorimotor
integration or in the translation of specific sensory data into
information for movement production (e.g. visual and somatosensory
transformation for reaching and body part location
data for control of body part movements). There are also
distinct frontostriatal circuits that play a role in action
sequencing. The circuit activated depends on whether the
action to be performed is prelearned or new, and on the
complexity of the cognitive demands of the task (Grafton
et al., 1995; Catalan et al., 1998). Apraxia can be found in
diseases of the basal ganglia, including Parkinson’s disease,
progressive supranuclear palsy (PSP) and Huntington’s disease,
and reportedly in isolated lesions of the basal ganglia.
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Table 1 Summary of apraxia types
Apraxia type Definition Clinical testing Localization
Limb-kinetic Loss of hand and finger
dexterity resulting from
inability to connect or
isolate individual movements
(Kleist, 1907)
All movements are affected—symbolic,
non-symbolic, transitive (i.e. using tools
and instruments, e.g. a hammer or a
hairbrush) and intransitive
(i.e. communicative gestures,
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:
All pathologically confirmed cases have
shown a degenerative process involving
frontal and parietal cortices (Fukui et al.,
1996) or primary motor cortex
(Tsuchiya et al., 1997)
Ideomotor Disorder of goal-directed
movement. Patient knows
what to do but not how to do
it. Disturbance of timing,
sequencing and spatial
organization of gestural
movement (Rothi and
Ochipa, 1991)
Impairment of pantomiming ability to
use tool. Movement is incorrectly
produced but the goal of the action can
usually be recognized. Abnormal errors
include spatial errors [i.e. (i) abnormal
amplitude; (ii) body-part-as-object
substitution, e.g. the patient uses his
own finger to represent a toothbrush
when asked to brush his teeth;
(iii) abnormal orientation of body part
performing the action, e.g. when the
patient is asked to pantomime brushing
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.
Anatomically diverse lesions mainly in
left hemisphere; typically involve parietal
association areas and white matter
bundles connecting frontal and parietal
association areas. Less commonly
premotor and supplementary motor
cortex are involved as well as basal
ganglia and thalamus. Unilateral lesions
of the left hemisphere in right-handed
patients produce bilateral deficits,
usually less severe in the left than in
the right limb
Ideational/
conceptual
Patient does not know what
to do. Content errors. This
terminology can be confusing
not only because definitions
of ideational and conceptual
apraxia vary among authors
(Ochipa et al., 1992; DeRenzi
and Lucchelli, 1988) but also
because a distinction between
the two is debated by some.
Error types include,
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
Inability to perform a multiple-step task
(e.g. prepare a letter to mail) owing to
errors such as perseveration.
Disturbance of single tool use—cannot
associate tool and object with the
corresponding action (e.g. unable to
choose a hammer to drive a nail or
correctly pantomimes an action when
requested to perform a very different
one) (Roth et al., 1988; Leiguarda et al.,
2000a; Ochipa et al., 1992)
No one anatomical area has been
identified, although in focal hemispheric
lesions, most have damage to left
hemisphere. Damage typically thought
to involve left parieto-occipital and
parietotemporal regions (Liepmann,
1920) but can also involve left frontal,
frontotemporal and temporal regions
with or without subcortical involvement
(Heilman et al., 1997)
1482 Brain (2005), 128, 1480–1497 C. Zadikoff and A. E. Lang
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Thus it seems likely that the basal ganglia are involved in
the transformation of action plans, or movement formulas,
to motor acts and, therefore, that dysfunction of the basal
ganglia itself could lead to errors of praxis.
Animal and human studies, using both electrophysiology
and functional imaging, have tried to define the role of the
basal ganglia in producing apraxia. Experimental studies in
monkeys have shown that putaminal lesions cause inaccurate
reaching (Kendall et al., 2000) and globus pallidus internus
lesions cause impaired reaching and grasping (Wenger et al.,
1999). Furthermore, positron emission tomography studies in
humans have found activation of the caudate/anterior putamen
during the performance of new or complex learned
sequences and activation of the middle putamen during
the performance of automatic sequences (Jueptner and Weiller,
1998). Electrophysiological studies have shown that there
are subsets of neurones in the external and internal segments
of the globus pallidus and substantia nigra pars reticulata that
increase their discharge frequency in relation to the amplitude
and velocity of movements (Georgopoulos et al., 1983)
whereas other pallidal neurones fire in relation to the direction
of arm movement (Mitchell et al., 1987). Moreover, there
are yet other pallidal neurones that change activity in
remembered sequential tasks and are influenced by the contextual
setting of the movement. This suggests that the basal
ganglia are involved in the production of both new and
learned movement sequences.
Using three-dimensional analysis, Leiguarda and colleagues
(2000b) studied the kinematic properties of a bread-slicing
movement in patients with Parkinson’s disease, PSP and multiple
system atrophy (MSA). This task was chosen in part
because of the repetitive, precise spatial movements required
to successfully complete it, recognizing that the basal ganglia
play a part in such movements. As will be discussed below,
two of the five patients with PSP, two of the eight with
Parkinson’s disease, and none of the five MSA patients
were felt to have ideomotor apraxia (IMA) clinically. Subjects
in all groups made some spatial errors, although the errors
made by the apraxic patients were more severe. The authors
felt that the milder errors in movement trajectory and external
configuration found in their patients supported the role of the
basal ganglia as an integral component of a brain network for
praxis. Additional damage to this network by extension of
pathology beyond the basal ganglia might then result in clinically
overt IMA, as seen in a subgroup of their patients.
Mink (1996) described the role of the basal ganglia in terms
of a gate that moderates response choice by selectively inhibiting
competing input from the cortex. As such, basal ganglia
lesions could disrupt the organized production of purposeful
movement by flooding the system with competing response
options (Mink, 1996). Supporting this notion is a study on
apraxia in Huntington’s disease, which found that apraxia
was related to disease severity. The authors postulated that
apraxia in this situation was due to an inability to effectively
gate competing motor programmes. If this was due to caudate
damage alone, which is typically seen early in the course of the
disease, then all patients with Huntington’s disease should
exhibit apraxia. Rather, those with longer disease duration
exhibited apraxia, again suggesting that apraxia is secondary
to damage to the basal ganglia plus other structures such as
surrounding white matter (Hamilton et al., 2003).
The suggestion that dysfunction of the basal ganglia alone is
insufficient to cause apraxia is further supported by the work
of Pramstaller and Marsden (1996), who reviewed 82 cases of
‘deep’ apraxia as a result of defined lesions, using imaging
(CT, and MRI if available) in 73 and neuropathological correlation
in 9. They found that most had lesions in the left
hemisphere, that isolated lesions of the putamen, thalamus, or
lenticular nucleus were uncommon (8 out of 82) and that
most patients actually had larger lesions involving damage to
the basal ganglia and/or thalamus as well as to the periventricular
and peristriatal white matter, disrupting association
fibres. In fact no cases of pallidal lesions alone caused
apraxia, and lesions of the caudate which caused apraxia
(n = 3) all had white matter involvement. Limb IMA was
the most common type of apraxia described (72/82), followed
by orofacial apraxia (OFA) in association with IMA (n = 37)
(Pramstaller and Marsden, 1996). Thus, as stated above,
although the basal ganglia may be involved in the production
of learned, skilled motor acts, it seems unlikely that isolated
lesions in the basal ganglia are capable of producing the disturbances
of motor performance subsumed under the concept
of apraxia. Rather, the basal ganglia alters the expression of
apraxia based on the context of movement required.
Disorders possibly misdesignated as
apraxia
Since the term apraxia was first coined, many conditions have
been called ‘apraxia’. If the current definition of apraxia is
applied, some conditions have probably been erroneously
designated as apraxias. Based on the literature, varying theories
can be advanced as to the pathophysiology underlying
these, although more work is needed to better classify them.
Two—apraxia of eyelid opening and apraxia of gait—are
commonly seen in movement disorder patients and will be
discussed below. Limb-kinetic apraxia, which to some represents
an elemental motor disturbance rather than a true
apraxia, will be discussed in the section on corticobasal degeneration
(CBD).
‘Apraxia’ of eyelid opening
Apraxia of eyelid opening is a syndrome characterized by the
inability to voluntarily open the eyes. The underlying pathophysiology
of ALO is not well understood, as evidenced by the
numerous other proposed designations, including inhibition
of levator palpebrae (Lepore and Duvoisin, 1985; Fahn, 1988),
akinesia of lid opening (Fahn, 1988) and lid freezing (Jankovic
et al., 1990). Goldstein and Cogan (1965) described the difficulty
in initiating the act of lid elevation in four patients with
basal ganglia disease and subsequent reports emphasized the
presence of this syndrome in extrapyramidal disorders, in
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particular PSP (Lepore and Duvoisin, 1985; Krack and
Marion, 1994; Boghen, 1997). There is considerable support
for the classification of many cases as a form of focal eyelid
dystonia. It is frequently found in association with blepharospasm,
and rarely occurs as an isolated entity (Elston, 1992). In
one population study ALO coexisted with adult-onset blepharospasm
in 75% of cases and with atypical parkinsonism in
25% (Lamberti et al., 2002). Among the overall patient population
seen in the authors’ movement disorders clinic, it was
isolated in 10 patients, associated with adult-onset dystonia in
13 (10% of all of their patients) and with parkinsonian syndromes
in 9 patients (2% of their parkinsonian patients; a
third of these had PSP). Recently ALO has been reported in up
to 31% of patients undergoing subthalamic nucleus deep
brain stimulation for Parkinson’s disease (Krack et al., 2003).
In patients with isolated ALO, the complaint is generally
the inability to open the eyes and not the forceful closure of
the eyes that constitutes blepharospasm. In one series (Krack
and Marion, 1994), apraxia of eyelid opening, referred to as
‘focal eye dystonia’ by the authors, was seen in two patients
with parkinsonism responsive to levodopa but in whom focal
dystonia (spasmodic torticollis and blepharospasm) preceded
the onset of parkinsonism. No ALO was seen in over
200 patients with idiopathic Parkinson’s disease without preceding
dystonia. Further support for considering it a form of
dystonia is the fact that some patients can use sensory tricks,
such as touching the sides of their eyes, to help initiate eyelid
opening and that many of the same triggers that aggravate
typical blepharospasm, such as bright light and looking up,
are also present in ALO. The response of ALO to treatment
with botulinum toxin in many patients also favours the consideration
of dystonia rather than a form of apraxia. Excessive
activity isolated to the pretarsal component of orbicularis
oculi probably accounts for both the absence of forced eyelid
closure in many and the response to botulinum toxin
(Jankovic, 1996; Defazio et al., 1998).
However, dystonia is unlikely to account for all cases of
ALO. Inappropriate inhibition of the levator palpebrae muscle
also seems to play an important role in the inability to
initiate eye opening in some patients with ALO. In a study
(Aramideh et al., 1994) of five patients referred for botulinum
toxin injections for ‘blepharospasm’ (four with blepharospasm
and levator inhibition and one with isolated levator
inhibition), the patient with isolated levator inhibition did
not have ongoing spasms of the eyelids but frequently experienced
involuntary drooping of the lids. No overt abnormal
contractions of the orbicularis oculi were noted in this patient;
electromyography showed no dystonic activity of the orbicularis
oculi, but frequent episodes of inhibition of levator
palpebrae activity were present. Here, as opposed to cases
with overactivity of pretarsal orbicularis oculi, botulinum
toxin failed to improve ALO.
Neither of these causes of eyelid opening dysfunction is
consistent with current concepts of the various types of
limb apraxia. Furthermore, when apraxia is evident in
orolingual muscles, eyelid opening difficulties are not an
associated or accompanying feature. Although tradition
will continue to encourage the use of the term ‘apraxia of
eyelid opening’, the weight of evidence supports not classifying
this as a form of apraxia.
‘Apraxia’ of gait
‘Apraxia of gait’ is another term that perhaps is a misnomer. It
is distinct from ‘leg apraxia’, and often the two do not coexist.
Leg apraxia can be tested using similar concepts to those that
guide examination of the upper limb. The patient can be asked
to pantomime tasks such as kicking a ball or stubbing a
cigarette out with a foot. However, leg apraxia has not
been routinely well studied in the assessment of praxis, and
most of the literature on apraxia concentrates exclusively on
the upper limb. This is in part because there is no standardized
testing of the lower limb and in part because there are fewer
movements (especially complex tasks) that can be tested in the
lower limb.
In contrast to the infrequent mention of leg apraxia,
‘apraxia of gait’ has garnered considerable attention; however,
the literature on this topic is quite complex, with various
examples of lumping and splitting ‘higher order’ gait disorders
(commonly with overlapping features using different,
often confusing, terminology). For instance, whereas some
assume that the terms ‘marche a petit pas’, ‘lower body
parkinsonism’, ‘vascular parkinsonism’, ‘Bruns’ ataxia’ and
‘gait apraxia’ all represent a similar gait subsumed under
the umbrella term ‘frontal gait disorders’ (Geschwind,
1975; FitzGerald and Jankovic, 1989; Schiller, 1995; Elble
et al., 1996), others have used this term to refer to different
gait patterns including frontal disequilibrium, isolated gait
ignition failure and freezing of gait (Geschwind, 1975; Nutt
et al., 1993; Poizner et al., 1995). Nutt et al. (1993) referred to
all of these gait disturbances as ‘higher level gait disorders’ to
signify dysfunction of the highest integrative sensorimotor
systems with intact basic motor and sensory functions. In
classifying these disorders they mixed clinical phenomenology
(gait ignition failure) with anatomical location (‘frontal gait
disorder’). In contrast, Liston et al. (2003) tried to avoid this
potential confound by simply classifying all ‘higher level gait
disorders’ (they limited their discussion to vascular causes) as
apraxic gaits and naming them according to the primary
problem seen, namely, ‘ignition apraxia’, ‘equilibrium
apraxia’ or ‘mixed gait apraxia’. This assumes that all higher
level gait disorders can be considered forms of apraxia; however,
this may not be appropriate. It has been postulated that
gait ignition failure (Freeman et al., 1993; Georgiou et al.,
1993) in Binswanger’s disease and lower body parkinsonism
owing to vascular disease occurs when damage to white matter
tracts alters communication between the basal ganglia and
the supplementary motor area, which may be involved in the
internal cueing and guidance of learned, skilled, motor acts of
the limbs (Chang et al., 1992; Hennerici et al., 1994). However,
‘gait apraxia’ typically exists without any evidence of
other forms of apraxia and patients with bilateral limb apraxia
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can have a normal gait (Geschwind, 1975; Thompson and
Marsden, 1987). Furthermore, in the strictest of definitions,
apraxia is the inability to perform ‘skilled or learned motor
acts’. However, locomotion is not a consciously learned
motor act but rather a repetitive motor pattern generated
by spinal mechanisms and modified by brainstem structures
(Shik and Orlovsky, 1976; Armstrong, 1988; Grillner et al.,
1995). One could argue that since walking is more ‘hard
wired’ there can be no such thing as an apraxic gait. With
a better understanding of the underlying anatomical and
functional pathology resulting in the clinical phenomenology,
perhaps a more uniformly acceptable nomenclature could be
devised and current confusion eliminated.
Apraxia in corticobasal degeneration
Clinical features
Apraxia has been described in a number of diseases of the
basal ganglia, such as Parkinson’s disease, PSP and Huntington’s
disease. Corticobasal degeneration is the disorder most
commonly associated with apraxia, which is present in up to
70% of patients with clinically diagnosed CBD (Leiguarda
et al., 1994). Corticobasal degeneration is characterized by
an akinetic-rigid syndrome combined with asymmetric,
lateralizing cortical signs including sensory loss, alien limb
behaviour and apraxia. In fact, apraxia is considered a hallmark
of CBD and is an important component of all proposed
diagnostic criteria (Litvan et al., 2003). However, this then
serves as an important source of clinical bias: a very high
proportion of patients with the clinical diagnosis of CBD
have apraxia because apraxia is believed to be a distinguishing
factor. Of equal importance, it is a source of misdiagnosis:
patients with parkinsonism plus apraxia are typically diagnosed
as having CBD rather than the more appropriate
designation of ‘cortical-basal syndrome’ (CBS) (Boeve et al.,
2003; Lang, 2003). The CBS may be caused by a variety of
underlying central nervous system pathologies, including
PSP, Alzheimer’s disease, dementia with Lewy bodies
(DLB) and frontotemporal dementias (see below).
In ‘classic’ CBD two types of apraxias have been emphasized:
ideomotor and LKA. Ideational apraxia has not been
discussed in detail. It has been suggested that this was a late
feature related to more severe dementia (Gibb et al., 1990).
However, since then it has been recognized that dementia may
be a common presenting feature of this disorder (Grimes et al.,
1998). Because this subgroup of patients are rarely given the
clinical diagnosis of CBD, the nature of apraxia seen with this
presentation has not been routinely evaluated. One study that
compared features associated with a cognitive presentation
with features associated with an extrapyramidal presentation
found that ideational apraxia was present in both groups and,
although less common, could occur in the absence of IMA
(Kertesz et al., 2000).
In patients with clinically diagnosed CBD, perhaps the most
commonly recognized type of apraxia—and the one that has
received the most attention—is ideomotor limb apraxia
(Table 1) (Leiguarda et al., 2000a). This is commonly bilateral
but typically asymmetrical, especially early in the disease
course (Rothi et al., 1985). The majority of errors made by
CBD patients with IMA consist of spatial, temporal and
sequencing errors, reflecting disruption of the ‘action production
system’ (Leiguarda et al., 2000a). As is also to be expected,
the errors are more frequently observed when performing
transitive than intransitive tasks and often improve when
the subject is given an object to use (Table 1). A number
of different studies (Pillon et al., 1995; Blondel et al., 1997;
Jacobs et al., 1999) have found that, although patients with
CBD make errors on gesture to command as well as imitation,
most have relative preservation of gesture recognition. Studying
a group of healthy volunteers using H2
15
O positron emission
tomography, Peigneux et al. (2004) showed that regional
cerebral blood flow increases in the medial frontal gyrus
(supplementary motor area) in the left hemisphere during
pantomime to command versus gesture recognition. This
conforms to anatomical divisions of praxis and the sites of
most profound pathological involvement in classical CBD, in
which the brunt of cortical pathology is in the superior frontal
and precentral and postcentral gyri (Dickson et al., 2000). For
example, in a study of patients with IMA resulting from
anterior and posterior lesions in the left hemisphere, only
those patients with a damaged parietal lobe had impairment
in the recognition of gestures (Heilman et al., 1982; Rothi
et al., 1985). The authors concluded that there are anterior
and posterior forms of IMA and that in the former gesture
recognition is preserved, whereas in the latter it is not. This is
because the visuokinaesthetic motor engrams are stored in the
parietal lobe and project to the supplementary motor area.
They proposed that the supplementary motor area transcodes
the space–time representation into an innervation pattern and
then projects this information to the primary motor cortex,
which directs the movement. In parietal lobe damage the
visuokinaesthetic information is disturbed and gesture comprehension
is impaired. In the anterior type of IMA, in which
there is damage to the supplementary motor area or to subcortical
white matter which disconnects motor areas from the
intact parietal lobe, the ‘praxicon’ (visuokinaesthetic engram)
is still intact and so patients can recognize gestures easily;
however, the information on how to perform the gesture is
lost (Heilman, 1985). Now there is evidence from brain
imaging studies in man (Steinmetz et al., 1989; Martin
et al., 1995) that, in fact, action recognition relies more on
temporal lobe structures than on the parietal lobe. In a study
comparing gesture recognition in patients with parietal lobe
damage to patients with premotor/supplementary motor area
damage and normal controls, minimal deficits in gesture
comprehension were found in the group with parietal lobe
damage and no deficits were present in the other two groups
(Halsband, 2001). The preservation of gesture recognition in
CBD implies frontal rather than parietal or temporal lobe
damage.
Limb-kinetic apraxia is one of the most striking features of
CBD, although it is not exclusive to this disorder (Leiguarda
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et al., 1997). It was first described by Kleist in 1907 as an
‘innervatory apraxia’ (Kleist, 1907), and then Liepmann
advanced the term ‘limb-kinetic apraxia’ (Liepmann, 1920).
He considered it the ‘most motor’ apraxia. Its existence as an
actual apraxia, rather than a consequence of more elemental
motor deficits, was largely ignored until its occurrence in CBD
was recognized (Geschwind, 1965; Heilman, 1985; Okuda
et al., 1992; Denes et al., 1998; Leiguarda et al., 2000a).
This has brought renewed interest in this type of apraxia.
Unlike IMA, which is typically bilateral, LKA is usually unilateral
and involves the most affected limb. Ideomotor apraxia
and LKA may be combined in the same limb. As outlined in
Table 1, LKA consists of impaired, coarse, ‘mutilated’ execution
of simple movements of the hand contralateral to the
cortical lesion. This is more evident distally than proximally
and is most notable for incoordination between fingers, as
seen in object manipulation tasks and fine finger movements.
This makes it the most difficult praxis disorder to distinguish
from bradykinesia, rigidity and dystonia—three movement
deficits commonly seen in CBD. Leiguarda et al. (2003) studied
the clinical and kinematic features of LKA in five patients
with clinically diagnosed CBD compared with five patients
with Parkinson’s disease and ten controls using a comprehensive
apraxic battery, three-dimensional motion analysis of
manipulative movements and motor evoked potentials. They
found that all five CBD patients demonstrated a unilateral
praxic deficit characterized by chaotic movement with
marked interfinger incoordination. Using a measure of movement
quality (QMC) they showed that the QMC was significantly
different in the CBD patients compared with controls
and most notably patients with Parkinson’s disease, suggesting
that neurological abnormalities such as bradykinesia and
rigidity alone are not able to explain LKA. They hypothesized
that dysfunction in the premotor cortex accounts for LKA.
The results of a study to assess processes underlying apraxic
disorders in CBD, using a cognitive model based on work by
Roy and Square (1985), also supported dysfunction of the
premotor cortex in LKA (Blondel et al., 1997). Finally, clinicopathological
evidence in five patients also supports the role
of damage to the premotor cortex underlying LKA in CBD
(Tsuchiya et al., 1997).
There is some debate, however, as to whether ‘limb-kinetic
apraxia’ is a misnomer as well. As mentioned previously,
initially Liepmann did refer to it as a true apraxia, yet others
disagreed and felt it was a primary motor deficit. With its
more recent recognition in CBD, it has generally been considered
an apraxia again; however, there are reasons to question
this classification. For example, damage to the pyramidal
tracts in primates is recognized to result in clumsy movements
characterized by an isolated deficit in independent finger
movements (Tower, 1940; Lawrence and Kuypers, 1968). Furthermore
in amyotrophic lateral sclerosis, often ‘loss of fractionated
movement is an early characteristic of hand
dysfunction’ (Weber et al., 2000), typically long before the
occurrence of other cognitive disturbances that might suggest
more widespread cortical involvement (Lomen-Hoerth et al.,
2003). These deficits are reminiscent of those considered
typical of LKA. Perhaps, then, LKA is better classified as a
primary or elemental motor dysfunction, with variable presentation
based on the extent of pathological changes, rather
than a type of apraxia.
The features of apraxia, including buccofacial apraxia, were
evaluated in 10 patients with clinically diagnosed CBD
(Leiguarda et al., 1994). Although seven patients had IMA
and three had both IMA and ideational apraxia, no patient
demonstrated buccofacial apraxia. In contrast to the lack of
OFA in this study, others have found this to be a common
feature in patients with CBD. Ozsancak et al. (2000) evaluated
dysarthria and OFA in 10 patients with clinically diagnosed
CBD: 9 patients had dysarthria, and voluntary movements of
the tongue and lips were impaired in all 10. Orofacial apraxia
for simple gestures was present in only four patients, whereas
impairment of sequential gestures was present in nine
patients. A rare presentation for CBD is the combination
of profound dysarthria and OFA (Lippa et al., 1991; Lang,
1992; Tanaka et al., 2001). One of our patients first noted
difficulties pronouncing words. He ultimately became anarthric
and exhibited apraxia of all facial movements at a time
when he had no other clinical deficits. Subsequent postmortem
study demonstrated a predominance of cortical
pathology in the region of Broca’s area in the dominant
left hemisphere in contrast to the more typical mesial predominance
of cortical pathology in CBD (Bergeron et al.,
1996).
Eye movement abnormalities that perhaps represent a type
of oculomotor apraxia can be seen in CBD as well. Cogan first
used the term ‘oculomotor apraxia’ to refer to ‘the inability to
initiate horizontal saccades in the head-fixed condition’. The
oculographic pattern is characterized by increased latencies
and decreased amplitude of horizontal saccades. In his series,
vertical saccades were normal (Cogan, 1953; Cogan and
Adams, 1953). Oculomotor apraxia is characteristic of two
diseases (both of which may demonstrate prominent movement
disorders): ataxia telangiectasia and ataxia oculomotor
apraxia. In the former, reflexive and voluntary saccade latencies
are prolonged, saccades are hypometric, velocities are
normal and head movements are used to initiate gaze shifts
(Stell et al., 1989; Lewis et al., 1999). This is quite typical of
Cogan’s initial description. In ataxia oculomotor apraxia, on
the other hand, latencies are said to be normal but saccades are
extremely hypometric (mimicking slow eye movements),
square wave jerks are present and synkinetic blinking is
used to compensate for lack of vestibulo-ocular reflex cancellation.
There is also a dissociation of eye–head movements
in which the head reaches the target before the eyes (Le Ber
et al., 2003, 2004). Although not well recognized at first, eye
movement abnormalities are a common manifestation of
CBD with characteristics reminiscent of the original description
by Cogan. Horizontal and vertical eye movements are
equally affected. Typically, the latency of saccades and not
their velocity is impaired. Initiation of horizontal saccades
can be delayed and some patients are unable to produce
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voluntary horizontal saccades, but this improves when something
is given to them to look at. Eye blinking and head
movements may be used to initiate voluntary saccades (Rebeiz
et al., 1967; Gibb et al., 1989; Lang et al., 1994b). In support of
considering this a manifestation of apraxia, one study found a
relationship between the apraxia score and the saccade latency
(Vidailhet and Rivaud-Pe´choux, 2000). The characteristics of
the eye movement abnormalities have been used to distinguish
CBD from PSP, where vertical saccade impairment is an
early feature, saccadic velocity (but not latency) is impaired,
the presence of square wave jerks is almost a uniform feature
and more errors are found on an antisaccade task (Vidailhet
and Rivaud-Pe´choux, 2000). In addition to characterizing
patients with the classical presentations of CBD or PSP,
these eye movement differences may also be useful in distinguishing
patients with more atypical presentations.
Rivaud-Pechoux et al. (2000) followed a group of 16 patients
(9 diagnosed with CBD and 7 with PSP), longitudinally with
electro-oculography and clinical exams 6 months apart, for a
mean of 37 months. They divided the CBD group into
‘probable’ (six out of nine) and ‘atypical CBD’ (three out
of nine) because the latter group did not fit all diagnostic
criteria for CBD (Litvan et al., 1997). In the probable CBD
group they found that horizontal saccades remained
impaired, characterized by increase in saccade latency of
reflexive visually guided saccades over time, and this was
more marked ipsilateral to the side in which apraxia predominated.
Horizontal saccade velocity did not decrease and
square wave jerks were infrequently present. However, in
the atypical CBD group, early square wave jerks, decreased
saccade velocity and a high percentage of errors in the antisaccade
test were more suggestive of PSP, and 4–6 months
following the electro-oculography recordings, the early
clinical diagnosis of CBD was revised to a diagnosis of PSP
(Rivaud-Pechoux et al., 2000) (Table 2).
Imaging and electrophysiology in
corticobasal degeneration and apraxia
Imaging studies have been used to support the diagnosis of
CBD. One of the most striking features, when clinical asymmetry
is evident, is the asymmetry of frontoparietal cortical
atrophy on MRI and CT, which is most notable contralateral
to the most severely affected side. In one series this asymmetry
was an almost constant feature with mild signal changes seen
in the atrophic cortex (mainly on fluid-attenuated inversion
recovery and proton density sequences) but minimal or no
abnormalities evident in the basal ganglia (Savoiardo et al.,
2000). Early in the disease the asymmetric changes may be
subtle, and late in the course bilateral abnormalities may be
evident. Recently volumetric imaging has been used to try to
differentiate between CBD and other parkinsonian syndromes
(Groschel et al., 2004), although none to our knowledge has
specifically studied apraxia. On the other hand, several functional
imaging studies have attempted to evaluate the pathophysiological
mechanisms underlying apraxia. In one study
that examined six patients with clinically diagnosed CBD (all
of whom had limb apraxia), regional cortical oxygen metabolism
was globally reduced, but more significantly so in the
superior prefrontal cortex, both lateral and mesial premotor
areas and in the sensorimotor, inferior parietal and superior
temporal cortices (Sawle et al., 1991). Striatal 18F-6fluorodopa
uptake was reduced in an asymmetric pattern
as well, with the caudate and putamen being involved in
all cases. Using a voxel-based approach and 18
flourodeoxyglucose
(18
FDG) positron emission tomography, another
study found a similar metabolic profile when 22 patients
with clinically diagnosed CBD were studied (Garraux et al.,
2000). Other positron emission tomography studies have
shown similar patterns of reductions in regional oxygen consumption
and glucose metabolism (Blin et al., 1992; Eidelberg
et al., 1991). The changes in regional cerebral blood flow have
also been studied using 99m
Tc-HMPAO SPECT (Frasson et al.,
1998; Markus et al., 1995; Morimatsu and Negoro, 1995).
These studies also showed significant reductions of regional
cerebral blood flow in the more affected hemisphere, with the
posterior frontal cortex, parietal lobe, caudate, thalamus and
putamen being most commonly affected. Okuda et al. (1995)
used N-isopropyl-p[123
I]-iodoamphetamine in two patients
with CBD. Both had LKA and one had constructional apraxia.
Both showed asymmetrical cortical hypoperfusion in the perirolandic
area, supporting the importance of dysfunction of
this area to LKA, and the patient with constructional apraxia
had unilateral hypoperfusion in the left posterior parietal area.
In an attempt to further refine our understanding of the
neural networks involved in IMA in CBD, attempts to correlate
18
FDG positron emission tomography data with a cognitive
neuropsychiatric assessment of apraxia have been
made. In one such study that evaluated 18 patients with
CBD, two complementary measures of apraxia were used.
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
attempt. The authors found that anterior cingulate hypometabolism
predominated in patients with CBD who performed
below the cutoff performance score for apraxia (14/18) and
that in those (7 out of 18) who could not correct their errors
(which occurred mainly in gesture imitation), hypometabolism
in the contralateral superior parietal lobe and supplementary
motor area predominated, although there was also
a deficit noted in the ipsilateral precentral gyrus (Peigneux
et al., 2001).
Other techniques that have been used to examine the central
mechanisms underlying limb apraxia in CBD include
somatosensory evoked potentials and transcranial magnetic
stimulation. For example, somatosensory evoked potentials in
five patients with CBD have been compared with those in 12
controls (Okuda et al., 1998). This study found that all
patients with limb apraxia, particularly LKA, had prolonged
N20 latencies following median nerve stimulation on the
more apraxic side, suggesting that somatosensory information
processing involving the parietal cortex might be
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involved. The problem with all these studies is not only that
most of the cases assessed were clinically diagnosed, and not
autopsy confirmed, but also, and more importantly for the
purposes of this discussion, that most patients studied had
other deficits, including dystonia, rigidity and cortical sensory
loss. Furthermore, many of the functional imaging studies
were done in the resting state, and not while undergoing
tests of praxis. Thus, it is impossible to be certain about
the relationship between the metabolic or electrophysiological
findings and the presence of apraxia.
Apraxia in other movement disorders
Other diseases can also give rise to the clinical picture typically
ascribed to CBD, and so the approach to diagnosis is shifting
from a single disease entity, CBD, to considering a number of
different diseases capable of exhibiting a similar clinical
phenotype, the CBS. This is comparable to the use of the
term parkinsonism to describe a clinical syndrome and
Parkinson’s disease to refer to one distinct pathological
cause of this syndrome. Several other pathological entities
may present with the CBS including PSP (Boeve et al.,
1999; Saint-Hilaire et al., 1996), Alzheimer’s disease (Ball
et al., 1993; Eberhard et al., 1996; Riley, 1996), Pick’s disease
(Lang et al., 1994a; Fukui et al., 1996; Boeve et al., 1999),
motoneuron inclusion disease with dementia (Grimes et al.,
1999), FTD-17 and Creutzfeldt–Jakob disease (Boeve et al.,
2003). These experiences suggest that it is the anatomical
distribution of the pathological changes, and not the exact
nature of this pathology, that results in the clinical phenotype.
Increasingly, autopsy series of cases diagnosed as CBD in life
are providing strong support for this concept. One of the
better examples of this is the experience reported from the
Mayo Clinic in which 47% of cases (16/34) diagnosed as CBD
in life had non-CBD pathology at autopsy. Almost without
exception it is the occurrence of apraxia, especially if asymmetrical,
associated with an akinetic-rigid syndrome, that
encourages this misdiagnosis (Boeve et al., 2003).
Progressive supranuclear palsy
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
signs of CBD, clinical overlap including the presence of
apraxia can pose a diagnostic dilemma (Litvan et al.,
1999). One study examined IMA in 14 patients with possible
PSP using diagnostic criteria of Litvan et al. (1996) and 12
patients fulfilling modified criteria for CBD from Lang et al.
(1994b) to determine whether there were any distinguishing
features between the two groups that might be useful clinically
(Pharr et al., 2001). Not surprisingly, the study found that the
overall praxis performance was worse in patients with CBD
than in those with PSP, although the latter also scored lower
than controls. Transitive tasks were more affected in PSP than
intransitive tasks. In CBD, transitive tasks were also more
affected than intransitive tasks, although both were affected,
and distal movements were more affected than proximal
movements. The authors concluded that intransitive tasks
are the best apraxia measure to distinguish between PSP
and CBD. Interestingly, in the CBD group distal movements
were considered most affected, suggesting that at least some of
the deficits in these patients could be accounted for by LKA in
addition to or instead of IMA.
Table 2 Apraxia in CBD
No. of
subjects
IMA LKA Ideational Orobuccal
Jacobs et al., 1999 6 CBD +, spatial and temporal
errors predominated
NA NA NA
Pillon et al., 1995 15 +, inclusion criteria
included presence of
apraxia
+ 3/15 0 +
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
included presence of LKA
NA 1
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.
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In a more recent study comparing only intransitive gestures
in 24 patients with CBD, 25 with PSP and 19 controls, total
apraxia scores were worse in both disease groups compared
with controls but CBD patients were consistently more compromised
than PSP patients in executing simple gestures. The
CBD cohort committed more awkwardness and spatial errors
than the PSP group, consistent with LKA, whereas sequencing
errors were similar among the two groups (Soliveri et al.,
2005). However, as emphasized previously, these two studies
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)
and often a source of diagnostic doubt or even an exclusionary
criterion for the other (i.e. PSP).
In another study comparing the presence of apraxia in 45
non-demented Parkinson’s disease patients, 12 with PSP, 10
with MSA and 12 patients with neuroleptic-induced parkinsonian,
bilateral IMA for transitive movements was present in
8 (75%) of the PSP cases, and 5 of these also had abnormalities
in intransitive movements (Leiguarda et al., 1997). None
showed errors of recognition of pantomimes and the total
apraxia scores correlated with cognitive disturbances, most
notably frontal lobe dysfunction. Of note, the authors
described five patients who showed ‘very awkward and clumsy
movements preceded by hesitation and unsuccessful attempts
when pantomiming any movement, irrespective of the type of
the gesture and the modality for evoking them’. They stated
that these difficulties were more than one could expect based
on the severity of rigidity and/or bradykinesia and they were
more obvious in the most affected hand. This description is
very suggestive of LKA. The authors also assessed patients for
features of orofacial and respiratory apraxia. Of the PSP
patients, 10 demonstrated OFA and 8 had respiratory apraxia.
The most striking feature noted was that of an overall final
correct performance preceded by long pauses during which
unsuccessful attempts were made. The authors commented,
however, that it was sometimes difficult to interpret the
nature of errors in the presence of the typical dystonic facial
appearance of PSP.
In a case report of a patient who fitted the clinical description
of PSP except that he had ‘moderate to severe apraxia’,
a postmortem demonstrated pathology consistent with PSP
but also senile plaques and tangles in the frontoparietal areas
suggestive of early Alzheimer’s disease (Pharr et al., 1999). The
authors suggested that when a patient with presumed PSP
demonstrates moderate to severe apraxia, the diagnosis of PSP
must be questioned. However, although brainstem and basal
ganglia pathology was initially emphasized in PSP, it has
become increasingly clear that cortical involvement is a feature
of the disorder. In a series of 10 cases of definite PSP,
cortical lesions were a constant feature and the density of
neurofibrillary tangles was highest in the precentral and angular
gyri (Verny et al., 1996). These cortical lesions may play a
significant role in the clinical phenomenology. In a clinicalpathological
study comparing PSP patients with classic presentation
to those with unusual signs (i.e. limb apraxia, focal
dystonia and arm levitation) and to those with CBD, PSP
patients with atypical signs had more severe cortical degeneration
than classic PSP patients but less cortical pathology
than patients with CBD. The cortical changes for all three
patient groups were most severe in the frontal lobe (Bergeron
et al., 1997). This again supports the argument made earlier
that it is the location of the pathology and the degree of
changes present, and not the nature of the pathological
changes, that lead to the clinical features of the CBS.
Idiopathic Parkinson’s disease
Apraxia has also been described in idiopathic Parkinson’s
disease. In the report by Leiguarda et al., 1997 discussed
above, bilateral IMA for transitive movements was found
in 27% (12) of the patients with Parkinson’s disease versus
75% of patients with PSP. The scores in the levodopa responsive
patients did not differ between the ON and OFF states. The
most common error type was spatial organization. None of
the Parkinson’s disease patients exhibited IMA for intransitive
tasks, had errors of recognition of pantomimes or had orofacial
or respiratory apraxia. As in the PSP group, apraxia
scores in patients with Parkinson’s disease correlated with
cognitive disturbances, namely frontal lobe dysfunction,
again emphasizing the importance of corticostriatal connections
in the generation of IMA. Importantly, there was no
correlation between apraxia scores and motor disability, as
measured by the Unified Parkinson’s Disease Rating Scale,
reemphasizing the point that limb apraxia can be examined in
the presence of, and is not explained by, classical parkinsonian
motor disability.
A few other studies have also examined praxis in idiopathic
Parkinson’s disease. One study compared the performance of
15 Parkinson’s disease patients with controls on two tasks: (i)
a symbolic representation of implement usage on verbal command
and on imitation and (ii) an imitation of non-symbolic
hand positions (Sharpe et al., 1983). The patients with
Parkinson’s disease performed at a lower gestural level on the
representational task and made more spatial errors on the
non-representational task. Another study evaluated imitation
of movement sequences in 42 patients with moderate to severe
Parkinson’s disease compared with controls (Goldenberg
et al., 1986). Again, the patients with Parkinson’s disease
had worse total apraxia scores, and these scores correlated
with visuospatial disability but not with motor severity. Not
surprisingly, Villardita et al. (1982) found that visuoperceptive
disabilities were responsible for ‘constructional apraxia’ in
a group of 20 patients with Parkinson’s disease. This disorder
is distinct from the forms of motor apraxia that are the main
subject of this review. Finally, a series evaluating motor praxis
(gestural functioning) in 22 non-demented patients with
relatively mild Parkinson’s disease (27% Hoehn & Yahr
stage 1; 69% Hoehn & Yahr stage 2) found that 63% of
these patients differed from controls in praxis performance
(Grossman et al., 1991). The majority of errors involved substitution
of body part for object. Although responses were
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slow, as might be expected as a result of bradykinesia, the
degree of gestural impairment did not correlate with degree of
motor disability. Finally, neuropsychological screening was
performed in this study but did not include specific tests
of perseveration and frontal lobe functions.
Dementia with Lewy bodies, Parkinson’s
disease dementia or Alzheimer’s disease
Dementia with Lewy bodies is another parkinsonian disorder
that may manifest apraxia. Distinguishing between diseases
that manifest the combination of parkinsonism and cognitive
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 neurofibrillary
tangles) often coexists with Lewy bodies (Crystal et al.,
1993; Lippa et al., 1994; McKeith et al., 1996). Some suggest
that the timing of apraxia in relation to the disease onset and
coexistence with other features (e.g. hallucinations, fluctuations
in level of awareness) may actually be of diagnostic
value. In a series evaluating the effect of coexisting Alzheimertype
lesion load, clinical and pathological features were
assessed in two groups of patients with DLB (del Ser et al.,
2001). The authors studied 35 Alzheimer’s disease, 11 pure
DLB and 18 Alzheimer’s disease plus DLB pathologically
confirmed cases. Not surprisingly, the most useful criteria
in distinguishing DLB from Alzheimer’s disease were similar
to the DLB consensus criteria, including hallucinations and
cognitive fluctuations, especially when present early in the
disease course (McKeith et al., 1996). The Alzheimer’s disease
and Alzheimer’s disease plus DLB patients in this series had
lower (worse) scores on the Extended Scale for Dementia.
Ideational apraxia was less frequent in the pure DLB group
(18%) compared with the groups with Alzheimer’s disease
(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 drawing
pentagons, has been found to be significantly worse in
patients with DLB (Cormack et al., 2004). Constructional
apraxia indicates a drawing disturbance without general
impairment of intelligence, visual or motor capabilities and
is usually caused by parietal lesions involving either hemisphere.
This study found that non-demented Parkinson’s disease
patients showed no abnormality of pentagon drawing but
those with Parkinson’s disease dementia made errors comparable
to the DLB group. This is not unexpected given the
current accepted continuum between Parkinson’s disease and
DLB and the clinical and pathological similarities between
Parkinson’s disease dementia and DLB (Burton et al., 2004;
McKeith and Mosimann, 2004). Although performance on
this task correlated with global cognitive dysfunction in those
with Alzheimer’s disease and Parkinson’s disease dementia,
this was not the case in those with DLB, in whom drawing was
linked only to perception and praxis. Therefore, one might
expect to find constructional apraxia earlier in the disease
course in DLB, whereas the occurrence of ideational apraxia
later in the course of the illness may be helpful in distinguishing
Alzheimer’s disease from DLB. Ideomotor apraxia, on the
other hand, has been found in up to one-third of patients with
mild dementia of the Alzheimer’s type (Della et al., 1987;
Taylor, 1994; Derouesne et al., 2000). Although, to our knowledge,
this feature, has not been assessed in DLB, the 27%
incidence in Parkinson’s disease found by Leiguarda et al.
(1997), especially in those with cognitive dysfunction,
might predict a similar or greater incidence in DLB. This
suggests that the presence of this type of apraxia early in
the course of a dementing illness may not be a very useful
distinguishing feature.
Multiple system atrophy
Relatively little has been published on the presence of apraxia
in MSA. No studies have examined apraxia in MSA separately,
but rather this group of patients is usually studied in comparison
with other parkinsonian syndromes. In the study by
Leiguarda et al. (1997), none of the patients with MSA (n =
10) or neuroleptic-induced parkinsonian demonstrated any
praxic errors. In another study by the same group, threedimensional
computer graphic analysis was used to study
the repetitive gesture of slicing bread. None of the four
patients with MSA had apraxia clinically, but on threedimensional
analysis they did show deficits in control of
the direction of the movement axis and in spatial patterns,
albeit that these were much milder than in the patients with
Parkinson’s disease and PSP (Leiguarda et al., 2000b). Finally,
in one series IMA was described in 2 of 19 patients with MSA,
although the majority of this group also showed evidence of
executive dysfunction (Monza et al., 1998). It is presumably
the relative lack of frontal/cognitive impairment in MSA
patients that spares the praxis system.
Huntington’s disease
Ideomotor limb apraxia also occurs in Huntington’s disease.
In a small series of nine patients, 33% met criteria for IMA
(Shelton and Knopman, 1991). The degree of apraxia correlated
with the duration of Huntington’s disease and with overall
motor disability but not with cognitive dysfunction,
chorea, dystonia, rigidity or bradykinesia. The authors postulated
that this was primarily due to basal ganglia dysfunction
because some of the patients who made errors had only
mild cognitive dysfunction [based on mini-mental state
examination scores and a 12-point auditory comprehension
test similar to the Token Test used for testing receptive aphasia
(De Renzi et al., 1982)], suggesting that cortical structures
were not yet involved; however, two of these patients had
mini-mental state examination scores of 21 and 22, respectively.
Because of the small sample size and the fact that the
most severely affected patients made the greatest apraxic
errors, a second group went on to study a larger set of patients
with a wider range of disease severity (Hamilton et al., 2003).
In 20 patients with Huntington’s disease, they also found a
1490 Brain (2005), 128, 1480–1497 C. Zadikoff and A. E. Lang
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Table3Studiesofapraxiainmovementdisorders
ReferenceNo.ofpatientsTypeofapraxiaTypesoferrorsMajordifferencesbetween
groups
Observations
PSPonly
Nathetal.,2003187PSP‘Eyelidapraxia’,present32,
absent52,notrecorded103
Nomentionofothertypes
ofapraxia
PSPandCBD
Pharretal.,200113CBD,14PSPPSPandCBDbothhadIMA.
Theybothhadmoredifficulty
withtransitivethan
intransitivetasks
CBDpatientsmademore
internalconfigurationerrors
andmoreunclassifiableerrors
thanPSP,butotherwise
performancewassimilar
acrossvariouserrortypes
CBDscoreswereworse
overallandshowed
preferentialworseningon
tasksrequiringdistalupper
extremitymanoeuvring
Monzaetal.,200324CBD,25PSPCBDpatientshadworse
totalapraxiascoresthanPSP
CBDpatientshadworse
apraxiaforwholeupperlimb
andhand/fingermovements
Soliverietal.,200524CBD,25PSP,19
controls
72%CBDand32%PSP
hadtotalscoresinthe
apraxiarange
Simplegestureperformance
wasworseinCBDgroup.
Sequencingerrorsdidnot
differbetweenthePSPand
CBDgroup.CBDpatients
mademoreawkwardnessand
spatialerrorsthanPSPgroup
CBDscoreswereworse
overall.ErrorsinCBD
werethoughttobe
consistentwithLKA
PD
Sharpeetal.,198315PDPDpatientsperformedat
lowergesturallevelon
representationaltasks
Patientsmademore
spatialerrorson
non-representationaltasks
Goldenbergetal.,198642PDIMAErrorsweremainlyin
sequencing
Degreeofimpairment
correlatedwithvisuos-
patialandvisuoperceptive
abilities
Grossmanetal.,199122PDpatients64%ofPDpatientshad
compromisedgestural
performance
Mostcommonerrorswere
bodysubstitution,anderrors
weremadeonrepresenta-
tionalmorethannon-
representationalgestures
Patientswerenot
dementedandscores
didnotcorrelatewith
motordeficit
OtherparkinonsiandisordersincludingPDandPSP
Leiguardaetal.,199745PD,12PSP,
10MSA,12NIP
IMAfortransitivein85%PSP
(8/12)and27%PD(12/45).
Orobuccalapraxiawasfound
in10PSPpatients.LKAwas
foundin5PSPpatients
Mainlyspatialerrors.
Noproblemswithgesture
recognitioninanygroup
IMAforintransitive
gestureswasfoundin
4PSP,noPD
CorrelationbetweenIMA
inPDanddeficitsinfrontal
lobe.InPSPIMAcorrel-
atedwithMMSE
Apraxia in movement disorders Brain (2005), 128, 1480–1497 1491
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Table3Continued
ReferenceNo.ofpatientsTypeofapraxiaTypesoferrorsMajordifferencesbetweengroupsObservations
Monzaetal.,199819MSA,19PSP,
14PD
Allgroupsmadesomeerrors
suggestiveofIMAwithPSP
beingthemostaffected.2/19
MSA.3/15PSPhadDeRenzi
scoresofpraxissignificance
Aftererrorsowingto
clumsiness,sequencingerrors
werethemostcommon
PSPhadmorevariable
errors,i.e.sequencing
(50%),clumsiness(30%),
location(10%)and
orientation(10%),
whereasMSAweredue
toclumsiness(85%)
andsequencing(15%)
Allsubjectsrecognized
gestures
HD
Hamiltonetal.,200320HD7/20(35%)withIMAGesturalimpairment
moreevidentfortransitive
thanintransitive
Apraxiacorrelatedwith
durationillnessandQNE
(motorimpairment),
especiallyeyemovement
deficitsbutnotwithMMSE
SheltonandKnopman,19919HDpatients33%(3)patientsexhibited
IMA,22%(2/9)madeno
apraxicerrorsand26%had
someimpairmentofgestures
Apraxiawaspresentfor
transitiveandintransitive
tasksbutnoerrorswere
madeinrecognitionof
gestures
Apraxiacorrelatedwith
durationofdisease
CBD=corticobasaldegeneration;HD=Huntington’sdisease;IMA=ideomotorapraxia;LKA=limb-kineticapraxia;MMSE=mini-mentalstateexamination;MSA=multiplesystem
atrophy;NIP=neuroleptic-inducedparkinsonism;PD=Parkinson’sdisease;PSP=progressivesupranuclearpalsy;QNE=quantifiedneurologicalexamination.
1492 Brain (2005), 128, 1480–1497 C. Zadikoff and A. E. Lang
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35% frequency of apraxia. Again the apraxia scores did not
correlate with chorea or cognitive status, but apraxic patients
did have more severe motor disability (namely, oculomotor
deficits) and longer disease duration. Although basal ganglia
neuronal loss might play a role in producing apraxia in
Huntington’s disease, it is important to acknowledge that
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
connections rather than pure basal ganglia dysfunction
underlies limb apraxia in Huntington’s disease.
Finally, although little has been written about OFA in
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 movements
is not explained by chorea or other elementary
motor disturbances. He described errors in performance of
simple tasks such as protrusion of the tongue and putting the
tongue into the cheek, as well as in more complex tasks such as
coughing, winking and whistling. These errors were often
accompanied by limb apraxia as well (Bruyn and Went,
1986) (Tables 3 and 4).
Conclusion
Various types of apraxia have been described in patients with
movement disorders particularly those combining parkinsonism
and cognitive dysfunction. It is important to recognize
that the presence of one type of apraxia does not exclude the
presence of other types and, in fact, multiple types can coexist
in the same patient. At times, apraxia is a dominant feature
that contributes substantially to the patient’s disability, especially
in the cases of ideational apraxia, in which everyday
object use is affected, and LKA, in which control over fine
finger movements is lost. On the other hand, motor disturbances
sufficient to constitute IMA may result in little or no
interference with function, particularly in the case of voluntary
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 disturbances
supports a role of the basal ganglia in praxis. The
term ‘apraxia’ is also misapplied to some motor disturbances
that may be seen in movement disorder patients. Finally, it is
unclear whether the motor dysfunction encompassed by the
term ‘limb-kinetic apraxia’ is best considered a form of
apraxia or a more ‘primary’ or ‘essential’ motor disturbance.
Further studies, including careful clinical assessment and analysis,
functional imaging, kinematic evaluations and prospective
clinical-pathological studies, are needed to clarify these
issues and answer the many questions that arise in the evaluation
of apraxia in movement disorder patients. Standardized
methods of evaluating such patients are required, with an
effort to reach wider consensus on the quantification, characterization
and applied terminology. Only then will it be
Table4Comparisonoflimbapraxiainselectedmovementdisorders
CBDPSPParkinson’sdiseaseDLBMSAHuntington’sdisease
LKA,distalhand,
unilateral
CommonUncommonNotpresentNotpresentNotpresentNotpresent
IMA,proximal
bilateral,but
asymmetric
Common;transitive
andintransitive
movementsaffec-
ted
Common;transitive
affectedmorethan
intransitive
movements
Uncommon;
intransitivemovements
notaffected;not
formallystudiedinPDD
Notroutinely
studied.Presence
probablycorrelates
withdegreeof
dementia
RarePresent
IdeationalapraxiaPresentUncommonNotpresentin
uncomplicated
Parkinson’sdisease;
notformallystudied
inPDD
Presentlaterin
diseasecourse
NotpresentRare
CBD=corticobasaldegeneration;DLB=dementiawithLewybodies;IMA=ideomotorapraxia;MSA=multiplesystematrophy;PDD=Parkinson’sdiseasedementia;PSP=progressive
supranuclearpalsy.
Apraxia in movement disorders Brain (2005), 128, 1480–1497 1493
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possible to begin to understand the role of the different neural
networks involved in producing these complex disorders of
movement.
Acknowledgements
The Morton and Gloria Shulman Movement Disorders
Center has been designated a Center of Excellence by the
National Parkinson’s Foundation. C.Z. was funded by the
Parkinson Society of Canada Boeringher-Inhgelheim
Clinical Fellowship. The authors would like to thank
Christine Klein and Sandra Black for their helpful comments
in preparation of this manuscript.
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