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  REVIEW ARTICLE Anosognosia for hemiplegia after stroke is amultifaceted phenomenon: a systematic reviewof the literature M. D.Orfei, 1 R.G. Robinson, 2 G. P. Prigatano, 3 S. Starkstein, 4 N.Ru «sch, 1 P. Bria, 5 C.Caltagirone 1,6 andG. Spalletta 1,6 1 IRCCS Santa Lucia Foundation, Laboratory of Clinical and Behavioural Neurology, Rome, Italy,  2 The University of IowaCarver College of Medicine, Iowa City, IA,USA,  3 Barrow Neurological Institute, Phoenix,  4 University of Western Australiaand Fremantle Hospital, Fremantle,  5 Catholic University of the Sacred Heart, Rome and  6 Department of Neuroscience,University of Rome‘‘Tor Vergata’’, Rome, ItalyCorrespondence to: Gianfranco Spalletta, MD, IRCCS Santa Lucia Foundation, Laboratory of Clinical and BehaviouralNeurology,Via Ardeatina, 306. 00179 Rome, ItalyE-mail: g.spalletta@hsantalucia.it Anosognosia is the lack of awareness or the underestimation of a specific deficit in sensory, perceptual, motor,affective or cognitive functioning due to a brain lesion.This self-awareness deficit has been studied mainly instroke hemiplegic patients, who may report no deficit, overestimate their abilities or deny that they areunable to move a paretic limb.Inthisreview, a detailedsearchoftheliteraturewas conductedtoillustrate clinicalmanifestations, pathogeneticmodels, diagnostic procedures and unresolved issues in anosognosia for motor impairment after stroke.English and French language papers spanning the period January 1990^January 2007 were selected usingPubMed Services andutilizingresearchwords stroke, anosognosia, awareness, denial, unawareness, hemiplegia.Papers reporting sign-based definitions, neurological and neuropsychological data and the results of clinicaltrials or historical trends in diagnosis were chosen. As a result, a very complex and multifaceted phenomenonemerges, whose variable behavioural manifestations often produce uncertainties in conceptual definitions anddiagnostic procedures. Although a number of questionnaires and diagnostic methods have been developed toassess anosognosia following stroke in the last 30 years, they are often limited by insufficient discriminativepower or a narrow focus on specific deficits. As a consequence, epidemiological estimates are variable andincidence rates have ranged from 7 to 77% in stroke. In addition, the pathogenesis of anosognosia is widelydebated. The most recent neuropsychological models have suggested a defect in the feedforward system,while neuro-anatomicalstudies have consistently reported on the involvement of the right cerebralhemisphere,particularlytheprefrontalandparieto-temporalcortex, aswellasinsula andthalamus.Wehighlighttheneed fora multidimensional assessment procedure and suggest some potentially productive directions for futureresearch about unawareness of illness.Keywords:  stroke; anosognosia; awareness; denial; hemiplegia Received December 23, 2006. Revised March 9, 2007. Accepted April12, 2007. Advance Access publication May 28, 2007 Introduction One of the most fascinating phenomena of the humanmind is consciousness, that is, the psychological function by which all individual cognitive experiences about the self andthe external world are integrated. In a number of neuropsychiatric disturbances this function is impaired(Flashman, 2002), causing interference with personalidentity or altering attention or awareness. One suchalteration is the apparent unawareness of impairmentwhich was referred to by Babinski (1914) as anosognosia(a-noso-gnosia Greek for ‘non illness knowledge’).Anosognosia is generally and comprehensively defined as adisorder in which a patient, affected by a brain dysfunction,does not recognize the presence or appreciate the severity of  doi:10.1093/brain/awm106  Brain  (2007), 130 , 3075^3090  The Author (2007).Publishedby Oxford University Pressonbehalfofthe Guarantorsof Brain. Allrightsreserved.For Permissions, please email: journals.permissions@oxfordjournals.org  deficits in sensory, perceptual, motor, affective or cognitivefunctioning (Bisiach and Geminiani, 1991; Prigatano, 1996;Antoine  et al  ., 2004). The term anosognosia is mostfrequently used to refer only to the unawareness of sensory-motor deficits following brain injury (Davies  et al  .,2005) and can be observed in cases of hemiplegia,hemianopia and aphasia (Bisiach  et al  ., 1986; Rubens andGarrett, 1991; Heilman  et al  ., 1998; Coslett, 2005). In thisreview, we will focus on anosognosia for hemiplegia,exclusively in the study of stroke patients. However, wewill review selected literature from traumatic brain injury (TBI) research and impaired self-awareness (ISA) in otherpatient groups for their potential sources of information forthe understanding of anosognosia in hemiplegic strokesubjects and when considering methodological and theore-tical issues in studying anosognosia for hemiplegia (Table 1).The understanding of this disturbance is not only of theoretical interest, but also has clinical implications of greatimportance. First, it seems to represent a negative prognosticsign, as it can compromise the course of recovery andrehabilitation (Pedersen  et al  ., 1996; Gialanella  et al  ., 2005;Prigatano, in press); secondly, the study of anosognosia forhemiplegia following stroke can significantly contribute toour understanding of higher cognitive functions andconsciousness (Pia  et al  ., 2004). Our goals are to comparedifferent pathogenetic models, to examine assessment anddiagnostic modalities, to clarify the relationship betweenanosognosia for hemiplegia in stroke patients and psycho-logical denial and to illustrate issues which still remainunresolved and suggest some directions for future research. Materials and Method A detailed search of the literature was conducted. For ourpurposes, the database was selected using PubMed Servicesutilizing the keywords: stroke, anosognosia, awareness,denial, unawareness, hemiplegia. We also hand-searchedrelevant journals. In addition, the bibliographies of allimportant articles were searched for further publications.The articles were restricted to English and French languageand spanned the period from January 1990 to January 2007.We chose papers reporting sign-based definitions, relevantempirical neurological and neuropsychological data andresults of clinical trials. Historically remarkable or concep-tually related articles were included as well. All articles cited inthis manuscript were judged by M.D.O and G.S. to be relevantand to meet the scientific and conceptual criteria listed. Results Matching the keywords ‘stroke and anosognosia’ 70 articleswere selected; other combinations such as ‘stroke andawareness’ highlighted 566 papers, ‘stroke and denial’43 papers, ‘stroke and unawareness’ 22 papers and ‘strokeand anosognosia and hemiplegia’ 28 papers. Most of thepapers were published in North America or Europe.Babinski’s work (1914) was the first to use the term‘anosognosia’ to identify lack of awareness of a motordeficit, even though the phenomenon had been describedby numerous clinicians prior to this time (Vallar  et al  .,2003). Since that time, anosognosia has been examinedprimarily in hemiplegia following stroke and TBI. Thesepatients deny their deficit, and overestimate their abilities,they state that they are capable of moving their pareticlimb and that they are not different than normal people.If they partially admit impairments, they will ascribe themto other causes (i.e. arthritis, tiredness, etc.). Often, theirfalse belief persists despite logical arguments and contra-dictory evidence and they may even produce bizarreexplanations to defend their convictions (Bisiach  et al  .,1986; Bisiach and Geminiani, 1991). Anosognosics usually do not show a catastrophic reaction, or desperation feelingsabout their condition and are unduly optimistic about theirprognosis and medical illness. Notably, they may be awareof other illnesses or admit to some non-motor-relatedimpairments. This is an indication of the modality-specificnature of anosognosia for hemiplegia (Ramachandran,1996) which may also be present in other forms of unawareness of illness (Ru¨sch and Corrigan, 2002). Otherphenomena which may be related to anosognosia for motorimpairment include various forms of bodily delusions calledsomatoparaphrenias. For example, patients may disclaimownership of their limb (Marcel  et al  ., 2004). Othermanifestations include a lack of concern about the deficit,termed anosodiaphoria or a hatred towards it, termedmisoplegia. Patients may also show an alteration of awareness in the direction of an overestimation of theextent of the deficit, with exaggerated complaints. Thesemanifestations, however, may be affected by other factors, Table1  Conceptualizations and definitions of anosognosia Authors Anosognosia Babinski (1914) The apparent lack of awareness of hemiplegia following an acute brain lesionHeilman  et al . (1998), Prigatano (1996) Clinical phenomena in which a brain dysfunctional patientis not aware of impaired neurological orneuropsychological function, which is obvious to the clinician and other reasonably attentiveindividuals.The lack of awareness appears specific to individuals deficits and cannot beaccounted for by hyperarousal or widespread cognitive impairmentAntoine  et al . (2004) The impaired ability to recognize the presence or appreciate the severity of deficits in sensory,perceptual, motor, affective or cognitive functioningSamsonovich and Nadel (2005) Reversible alteration of the autobiographicalmemories related to a personal deficit, together with the awareness of these memories (and without any awareness of the alteration) 3076  Brain  (2007), 130 , 3075^3090 M. D.Orfei  et al .  such as mood disorders, past experiences, current stressors,etc. The empirical research focusing on these disordersis very sparse, therefore we will not include thesephenomena in our definition of anosognosia. Epidemiology Empirical studies have reported wide ranging frequencies of anosognosia in patients with hemiplegic stroke.Classical studies on prevalence rates for anosognosia formotor impairment have ranged from 33 to 58% in strokevictims (Cutting, 1978; Bisiach  et al  ., 1986). In other morerecent studies, however, they ranged from 10 to 17%(Appelros  et al  ., 2002, 2003; Baier and Karnath, 2005). Thisvariability is probably related to differences in diagnosticcriteria used by different investigators, and differences intime since stroke (Pedersen  et al  ., 1996; Jehkonen  et al  .,2006). For example, Pia  et al  . (2004) found prevalence ratesranging from 20 to 44% depending upon the time elapsedsince brain injury. In fact, several authors noted a progressiverecovery from anosognosia for hemiplegia following strokewithin the first 3 months, making recovery more probable inthe acute phase than in the chronic period (Cutting, 1978;Pedersen  et al  ., 1996; Jehkonen  et al  ., 2000; Marcel  et al  .,2004). Thus, although one-third of hemiplegic patients may still show anosognosia during the chronic phase of the illness,the time of the assessment is crucial. Another factor in thevariable prevalence rates for anosognosia for motor impair-ment after stroke may be the diagnostic criteria used.For example, Baier and Karnath (2005) found that anumber of researchers diagnosed anosognosia when patientsscored 1 on the Bisiach’s scale, a score assigned when thedisorder is reported by the patient only after specificquestions. Therefore, the deficit is evident to the subject,but it may be relatively mild and subjectively less prominentto him than other co-occurring symptoms. As a consequence,these authors reported a lower rate of 10–18% of anosognosiain acute or subacute stroke patients based on a score of atleast 2 on the Bisiach’s scale (Bisiach  et al  ., 1986).Finally, prevalence variations in epidemiological studiescan be influenced also by patient selection bias. It occurs innon-randomized studies and limits their ability to generalizetheir results as well as understanding the study’s outcome(Swenson, 1980; Mark, 1997). As it is evident from Table 2,different researches report findings from different settings,such as rehabilitation and acute hospitals or the community.Moreover, the variability of the data is striking not only among heterogeneous settings, but also among studiesconducted in comparable settings. For example, Table 2shows that anosognosia varies from 8 to 34% in acutehospital studies. It may depend on the breadth of thecatchment area of each hospital and the number of bedsavailable for acute stroke patients. The consequence couldbe that only patients with higher severity of stroke will beadmitted. This can increase the probability of diagnosinganosognosia for motor impairment because severity of awareness deficit seems to be positively correlated with thesize of the lesion and therefore with the severity of the strokeand of the motor impairment (Hier  et al  ., 1983 a ,  b ; Pedersen et al  ., 1996; Hartman-Maeir  et al  ., 2003). A good example of reduced patient selection bias is the Copenhagen Study (Jørgensen  et al  ., 1995; Pedersen  et al  ., 1996), where the rateof stroke patients admitted in the acute hospital is 88% of allcases regardless of age, severity and pre-stroke conditions.Thus, this study, although defined as hospital-based,  de facto can be considered almost community-based. Inclusioncriteria constitute another factor potentially influencingepidemiological data. Indeed, decision to include patientswith different laterality of lesion, severity of aphasia andpre- and post-stroke dementia (Appelros  et al  ., 2007) may influence the rate of anosognosia for motor impairment.In contrast, no significant differences in frequency of anosognosia have been related to gender or age (Pedersen et al  ., 1996; Pia  et al  ., 2004; Appelros  et al  ., 2007). Pathogenesis Most aetiological hypotheses about anosognosia for hemi-plegia in stroke can be subdivided into three themes:neuropsychological models, hemispheric damage modelsand intra-hemispheric localization models (Frith  et al  .,2000) (Table 3). Neuropsychology Some neuropsychological models consider anosognosia forhemiplegia after stroke to be the consequence of a globalcognitive impairment (McGlynn and Schacter, 1989; Levine et al  ., 1991). Although some relationships between cognitivefunction and awareness of motor deficit have beendemonstrated, recent data do not associate anosognosiafor motor impairment after stroke with either globalcognitive impairment or a confusional or delirious state(Starkstein  et al  ., 1992; Coslett, 2005). Thus, althoughglobal cognitive impairment does not appear to be a majorcausal factor, it may be a predisposing factor or may lead togreater severity of anosognosia for hemiplegia followingstroke (Marcel  et al  ., 2004; Vuilleumier, 2004).Other researchers have focused on specific cognitivedeficits. For instance, Starkstein and colleagues (1992)suggested that anosognosia for hemiplegia after stroke may result from memory impairment. As Marcel and colleagues(2004) argue, it could derive from a failure to transfer new information from working memory into long termmemory. Anosognosic patients would be able to recognizetheir motor and/or sensory deficits when instancesdemonstrating these impairments occur, but they wouldfail to integrate them into their body self-image in long-term memory. Inconsistent forms of awareness are not rarein this population of patients. For instance, some subjectsmay complain they are paralysed and yet attempt bilateralactions, others deny paralysis but accept to stay in bed orin a wheelchair (Marcel  et al  ., 2004; Vuilleumier, 2004). Anosognosia after stroke  Brain  (2007), 130 , 3075^3090 3077  Table 2  Frequency of anosognosia among patients with hemiplegia Authors Setting Sample Time elapsed from stroke Diagnostic tools Rate of anosognosia Cutting (1978) Article not available 100 acute hemiplegic patients Article not available Cutting’s questionnaire 58% RBD14% LBDBisiach  et al . (1986) Acute hospital 36 RBD 1^37 days Bisiach’s Scale 33%Starkstein  et al . (1992) Acute hospital 80 stroke patients 2^12 days Anosognosia questionnaire 34% Total:10% mild11%moderate13% severeStone  et al . (1993) Acute hospital 69 RBD102 LBD 2^3 days Standardized test battery(not available)33%Pedersen  et al . (1996) Acute hospital 566 acute stroke patients Within 3 days Bisiach’s Scale 21%Maeshima  et al . (1997) Acute hospital 50 RBD Within 30 days Unstructured questionsabout the deficit24% Jehkonen  et al . (2000) Acute hospital 56 RBD Within10 days Cutting’s questionnaire 7%Hartman-Maeir  et al . (2001) Rehabilitation hospital 29 RBD17 LBD 4^8 weeks Unimanual and bimanual tasksplus explicit verbal measure26% total:17% RBD 9% LBDAppelros  et al . (2002) Community 349 stroke patients Within 30 days Anosognosia questionnaire 17% ( n ¼ 48:15 mild; 8 moderate;25 severe)Hartman-Maeir  et al . (2003) Rehabilitation hospital 36 RBD 24 LBD 4^8 weeks; Patient CompetencyRating Scale77% total: 47% RBD 30% LBDFarne '  et al . (2004) Rehabilitation hospital 33 RBD Within 6 weeks Cutting’s questionnaire(adapted version)31%Marcel  et al . (2004) Rehabilitation hospital 65 stroke patients 55^79 days Awareness interview 23% unaware of motorefect 80% unaware of somatosensory defectBaier and Karnath (2005) Rehabilitation hospital 72 RBD 56 LBD Within15 days Bisiach’s Scale 10%Berti  et al . (2005) Not available 30 RBD Within 60 days Bisiach’s Scale 3% affected by anosognosiawithout neglect; 57% affectedby anosognosia with neglectAppelros  et al . (2007) Community 272 stroke patients 1^4 days Anosognosia questionnaire 17%Abbreviations: RBD ¼ right brain damaged patients, LBD ¼ left brain damaged patients.  3   0   7   8   B  r  ai    n   (   2   0   0   7    )    , 1   3    0     , 3   0   7   5  ^ 3   0   9   0  M .D . Or f    ei     e  t    al      .
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