ORIGINAL CONTRIBUTION Association of Ideomotor Apraxia With Frontal Gray Matter Volume Loss in Corticobasal Syndrome Edward D. Huey, MD; Matteo Pardini, MD; Alyson Cavanagh, BS; Eric M. Wassermann, MD; Dimitrios Kapogiannis, MD; Salvatore Spina, MD; Bernardino Ghetti, MD; Jordan Grafman, PhD Objective: To determine the brain areas associated with matter volume in the left supplemental motor area, pre- specific components of ideomotor apraxia (IMA) in cor- motor cortex, and caudate nucleus of patients with CBS. ticobasal syndrome (CBS). The overall degree of apraxia was independent of the side of motor impairment. Praxis to imitation (vs command) Design: Case-control and cross-sectional study. was particularly impaired in the patients with CBS. Pa- tients demonstrated equal impairment in transitive and Participants: Forty-eight patients with CBS and 14 con- intransitive praxis. trol subjects. Conclusions: In patients with CBS, IMA is associated with Intervention: Administration of the Test of Oral and left posterior frontal cortical and subcortical volume loss. Limb Apraxia. Despite showing left frontal volume loss associated with IMA, patients with CBS have particularly impaired imita- Main Outcome Measures: Differences between pa- tion of gestures. These findings suggest either that the IMA tients with CBS and healthy controls and associations be- of CBS affects a route of praxis that bypasses motor en- tween areas of gray matter volume and IMA determined grams or that motor engrams are affected but that they ex- by voxel-based morphometry in patients with CBS. ist in areas other than the inferior parietal cortex. Results: Overall, IMA was associated with decreased gray Arch Neurol. 2009;66(10):1274-1280 ORTICOBASAL SYNDROME parts as objects),9 ideational (failure to se- (CBS) is a rare neurologic quence task elements correctly),7,10 and con- disorder characterized by ceptual (failure to use tools correctly).11 progressive asymmetric Ideomotor apraxia is the most commonly apraxia and rigidity with observed type of apraxia in CBS,5,6 as well Cother findings of cortical (eg, alien limb, cor- asthemoststudied.10 Severalresearchershave tical sensory loss, myoclonus, and mirror proposedthatsuccessfulpraxisofteninvolves movements) and basal ganglia (eg, brady- the use of motor engrams.12-14 The term en- kinesia and increased resistance to passive gram has been variably defined in the litera- movement) dysfunction.1,2 Corticobasal syn- ture. In this study, we define an engram as drome is defined as a clinical syndrome aris- a “visuokinesthetic motor memory” of a pre- ing from dysfunction of specific brain areas. viously performed action that facilitates re- It is associated with the neuropathological production of the action.13,15 It has been pro- changes of corticobasal degeneration3; how- posed that these engrams are contained in ever, the clinical syndrome of CBS can be the left inferior parietal lobe13,16 and com- observed with other underlying pathologi- municated to premotor and motor areas that cal conditions.4 are important in programming the move- Apraxia is a core clinical feature of ments coded for by the parietal representa- CBS1,2,5-8 and is defined as impaired pro- tion.13 In support of this theory, the left pa- duction of purposeful skilled movements rietal lobe is the lesion site most commonly that is not explained by deficits in elemen- associated with apraxia,17-22 and the left pa- tal motor functions, sensation, cognition, rietal lobe is activated with praxis in healthy or language.6 Apraxia has been classified individuals.23 However, damage to the left into different types: oral, limb-kinetic (loss frontalcortex,especiallytheleftmiddlefron- of hand and finger dexterity), ideomotor talgyrus,19 andsubcorticalstructures24 isalso (IMA) (deficits in executing goal-directed sufficient to cause IMA in the absence of pa- movements characterized by the presence rietal lesions.18 Author Affiliations are listed at of temporal and/or spatial errors as well as If motor engrams are damaged (from the end of this article. improper spatial orientation and use of body injury to the left inferior parietal lobe), pa- (REPRINTED) ARCH NEUROL / VOL 66 (NO. 10), OCT 2009 WWW.ARCHNEUROL.COM 1274 ©2009 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 Table 1. Subject Characteristics Patients With CBS Healthy Controls ␹2 or t Value (n=48) (n=14) for Difference P Value Sex, No. M/F 25/23 8/6 ␹2=0.001 .98 Age at onset, mean (SD), y 61 (9) NA NA NA Age at testing, mean (SD), y 66 (9) 60 (6) t=2.44 .02 Handedness, No. R/L/ambidextrous 43/4/1 14/0/0 ␹2=1.586 .45 Education, mean (SD), y 15 (3) 17 (4) t=1.99 .051 MDRS2 total raw score, mean (SD) (total possible, 144) 116 (24) 139 (3) t=3.65 .006a Initial side of symptoms, No. L/R/unclear 25/21/2 NA NA NA Side tested, No. L/R/both 33/13/2 NA NA NA Abbreviations: CBS, corticobasal syndrome; L, left; MDRS2, Mattis Dementia Rating Scale 2; NA, not applicable; R, right. a Significant at a Bonferroni-corrected level of PϽ.05. tients should have impairment of gesture recognition, imitation and equal impairment in the production of whereas frontal lesions should be associated with apraxia meaningful and meaningless gestures (ie, representa- with preserved gesture recognition.13,14 Thus, patients with tional IMA). If their IMA is more associated with frontal IMA from frontal damage should be able to recognize ges- dysfunction, they should show an advantage in produc- tures and perform them to imitation more easily than to ing gestures to imitation compared with command and command.13,25 Two studies found that patients with CBS meaningful gestures compared with meaningless ges- had IMA to command to a greater degree than to imita- tures (ie, dynamic IMA). tion or recognizing actions, suggesting a relative preser- 6,14 vation of movement representations, implicating fron- METHODS tal rather than parietal damage (although this was not directly tested). A deficit of functions associated with the frontal lobe in patients with CBS has been linked with SUBJECTS apraxia.6,26,27 In the 2-route model,9,28,29 separate routes are pro- Forty-eight patients with CBS seen consecutively in the Na- posed for gesture production and imitation depending tional Institute of Neurological Disorders and Stroke Cogni- tive Neuroscience Section clinic participated. All were en- on whether the gesture has meaning. The indirect or “lexi- rolled in an ongoing natural history study of CBS and related cal” route, associated with the inferior parietal lobe, is disorders. Patients were referred by outside physicians or self- used to process meaningful gestures and has access to referred. The diagnosis was confirmed by a neurologist with information about the gesture, including engrams. Dam- expertise in movement disorders and behavioral neurology age to this route can produce “representational” IMA char- (E.M.W.) and a neuropsychologist (J.G.) according to pub- acterized by greater impairment of transitive (involving lished criteria.1 All patients assigned durable power of attor- objects or tools) than intransitive (symbolic) gestures and ney before enrollment and assignees gave written informed con- equal impairment in the imitation of meaningful and sent for the study, which was approved by the institutional meaningless gestures.29 The direct route, associated with review board of the National Institute of Neurological Disor- frontoparietal structures, is used for the processing of ders and Stroke. Demographic and clinical data are presented in Table 1. Five patients died and their brains were obtained meaningless gestures and bypasses engramatic informa- at autopsy. All of them had a neuropathological diagnosis of tion. Damage to this route can produce “dynamic” IMA, corticobasal degeneration, according to standard criteria.3 The which is characterized by equal impairment of transi- healthy control subjects were recruited from the local commu- tive and intransitive gestures, but an advantage in imi- nity by advertisement and were age and education matched to tating meaningful gestures.29 This model is similar to that the patients (Table 1). All healthy controls underwent an in- proposed for language processing in which patients with terview and neurologic examination. The exclusion criteria for transcortical sensory aphasia can repeat words without the patients with CBS included a diagnosis of any neurodegen- understanding them.9 Other researchers have also pro- erative illness other than CBS, lack of a caregiver who could posed models of praxis that posit the utilization of sepa- assist with participation in the study, behavioral symptoms that rate systems of action knowledge and perceptual and mo- would preclude data collection, and any other medical or so- 30 cial condition that would, in the opinion of the investigators, tor processes to perform actions. preclude participation. The exclusion criteria for the healthy This study attempts to better characterize IMA in CBS controls included any active neurologic or psychiatric condi- and elucidate its neuroanatomic basis. Corticobasal syn- tion, use of any neurologic or psychiatric medications, and sig- drome is a good system in which to examine the relative nificant abnormalities on neurologic examination, magnetic reso- contributions of frontal and parietal cortices to IMA be- nance imaging, or neuropsychological testing. cause the patients often have both posterior frontal and parietal dysfunction. A second goal is to integrate these APRAXIA ASSESSMENT findings into current theories of IMA. Specifically, we hy- pothesize that if the patients have IMA associated with The measure of apraxia used in this study was the Test of Oral and dysfunction of engrams contained in the inferior pari- Limb Apraxia (TOLA).31 In the TOLA, each subject was asked to etal cortex, they should have especially poor praxis to perform each gesture first to verbal command (eg, “show me how (REPRINTED) ARCH NEUROL / VOL 66 (NO. 10), OCT 2009 WWW.ARCHNEUROL.COM 1275 ©2009 American Medical Association.