A diagnostic test of unawareness of bilateral motor task abilities in anosognosia for hemiplegia

Anosognosia for hemiplegia (AHP) is conventionally defined/diagnosed by generic questions about awareness of limb plegia. However, unawareness of inability to perform tasks requiring bilateral use of limbs is more widespread and outlasts generic unawareness of plegia. Some patients consistently overestimate bilateral task ability. Our aim was to assess how well specific questions about bilateral task ability predict whether patients consistently overestimate their abilities. Six statistical indices were calculated to rank the questions for predictiveness of consistency of overestimation of bilateral task ability. Overall, bimanual questions are better predictors than bipedal questions of consistent overestimation. Three bimanual and two bipedal questions had both sensitivity and specificity above 80%. On the basis of accuracy and discriminability, one bimanual and one bipedal question that performed maximally could be used for a quick bedside heuristic index. For a more thorough diagnostic, especially for research, five bimanual and two bipedal questions were good predictors, and should be used. For both purposes, such tests should be given in combination with conventional generic questions assessing awareness of limb plegia, since the two kinds of question reflect different kinds of unawareness of motor incapacity.     

Unawareness of motor impairment and emotions in right hemispheric stroke: a preliminary investigation

BACKGROUND: Awareness may lack in some stroke patients who are not capable of evaluating the nature and severity of illness. Thus, unawareness may have different forms such as anosognosia, neglect, and alexithymia or unawareness of emotions. In this study we investigated the relationship among anosognosia, neglect, alexithymia, and cognition. METHODS: Fifty consecutive right stroke inpatients were approached within the first 3 months from the acute event. Anosognosia was measured with the Bisiach scale, alexithymia with the TAS-20 scale and neglect with line crossing, letter cancellation, figure and shape copying, and line bisection tests. A neuropsychological test battery was used to measure different areas of cognition. RESULTS: despite the strong comorbidity rate among the different forms of unawareness, there are patients who suffer from pure forms of these types of lack of awareness. A multivariate logistic regression model evidenced that presence of neglect (OR = 10.3; 95% CI = 1.4-76.3; p = 0.023) and more difficulty in describing feelings (TAS-20 F2 subscore; OR = 1.3; 95% CI = 1.1-1.7; p = 0.014) were the only predictors of anosognosia. In addition, anosognosics with alexithymia performed worst in a frontal task such as the verbal fluency task (p = 0.042) and in the verbal span forward task (p = 0.026) than pure anosognosics. CONCLUSIONS: Anosognosia for motor impairment is strictly associated with a specific form of unawareness of emotions. Future studies have to clarify if frontal cognitive impairment previously described in anosognosics is a manifestation of unawareness of emotions or anosognosia for motor impairment.     

Explicit and implicit anosognosia or upper limb motor impairment

If asked directly, anosognosic patients deny or seriously underestimate their motor difficulties. However explicit denial of hemiplegia does not necessarily imply a lack of insight of the deficit. In this study we explored explicit and implicit awareness for upper limb motor impairment in a group of 30 right-brain damaged patients. Explicit awareness was assessed using a questionnaire (the VATAm) in which patients are asked to rate their motor abilities, whereas implicit awareness was assessed by means of a newly developed test (BMT - bimanual task). This test requires the performance of a series of bimanual tasks that can be better performed using two hands, but could also be performed using one hand only. With the BMT, patients’ performance rather than their verbal reports is evaluated and scored as an index of awareness. Paretic patients with anosognosia tend to approach these tasks as if they could use both hands. Our findings showed that explicit and implicit awareness for motor deficits can be dissociated, and they may be differently affected by feedback suggesting that different underlying mechanisms may account for the multi-factorial phenomenon of anosognosia.     

Error-based training and emergent awareness in anosognosia for hemiplegia

Residual forms of awareness have recently been demonstrated in subjects affected by anosognosia for hemiplegia, but their potential effects in recovery of awareness remain to date unexplored. Emergent awareness refers to a specific facet of motor unawareness in which anosognosic subjects recognise their motor deficits only when they have been requested to perform an action and they realise their errors. Four participants in the chronic phase after a stroke with anosognosia for hemiplegia were recruited. They took part in an “error-full” or “analysis of error-based” rehabilitative training programme. They were asked to attempt to execute specific actions, analyse their own strategies and errors and discuss the reasons for their failures. Pre- and post-training and follow-up assessments showed that motor unawareness improved in all four patients. These results indicate that unsuccessful action attempts with concomitant error analysis may facilitate the recovery of emergent awareness and, sometimes, of more general aspects of awareness.     

Unawareness of deficits after right hemisphere stroke: double-dissociations of anosognosias

OBJECTIVES: The aim was to study whether anosognosia for hemiparesis, anosognosia for neglect and general unawareness of illness double-dissociate, indicating that anosognosias are specific and independent impairments of awareness. On the other hand, anosognosias may be associated with one another and with general cognitive dysfunction, which decreases awareness of deficits. The persistence and predictive value of anosognosias was examined during a 1-year follow-up. PATIENTS AND METHODS: Fifty-seven consecutive patients with acute right hemisphere infarction underwent neurological and neuroradiological examinations, neuropsychological testing and an interview 10 days, 3 months and 1 year after onset. RESULTS: Anosognosia for neglect and anosognosia for hemiparesis double-dissociated, as did unawareness of illness and anosognosia for neglect. Patients showing unawareness of illness or anosognosia for neglect and anosognosia for hemiparesis had poorer orientation and verbal memory than patients who were aware of these defects. Unawareness of illness and anosognosia for hemiparesis disappeared during 3-month follow-up. CONCLUSION: Double-dissociations demonstrate that anosognosias for different defects are independent and specific impairments of awareness, although general cognitive disorder may also reduce awareness of defects. Unawareness of illness and anosognosia for hemiparesis disappear rapidly and can hardly be direct causes of poor long-term recovery. However, transient anosognosia may be associated with persistent disorders which result in poor outcome.     

Anosognosia during Wada testing.

Anosognosia, the verbally explicit denial of hemiplegia, is more often reported after right- than left-hemisphere lesions. However, this asymmetric incidence of anosognosia may be artifactual and related to the aphasia that often accompanies left-hemisphere lesions. Anosognosia has been attributed to psychological denial and the emotional changes associated with hemispheric dysfunction. Eight consecutive patients undergoing intracarotid barbiturate (methohexital) injections as part of their presurgical evaluations for intractable epilepsy were assessed for anosognosia after their hemiplegia and aphasia had cleared. After their left-hemisphere anesthesia, all subjects recalled both their motor and language deficits. However, after right-hemisphere anesthesia, none of the eight patients recalled their hemiplegia. These results suggest that anosognosia is more often associated with right- rather than left-hemisphere dysfunction and that it cannot be attributed to either psychological denial or the emotional changes associated with hemispheric dysfunction.     

The pathogenesis of anosognosia for hemiplegia

We compared patients with unawareness of hemiplegia lasting more than 1 month after right hemisphere stroke with other patients with right hemisphere stroke who became aware of hemiplegia within a few days after onset. Patients with persistent unawareness invariably had severe left hemisensory loss and usually had severe left spatial neglect. They were almost always apathetic; their thought lacked direction, clarity, and flexibility, and they had at least moderate impairment of intellect and memory. Their right hemisphere strokes were large and always affected the central gyri or their thalamic connections and capsular pathways. In addition, there was evidence of at least mild left hemisphere damage, most commonly caused by age-associated atrophy. The pathogenesis of anosognosia for hemiplegia may involve failure to discover paralysis because proprioceptive mechanisms that ordinarily inform an individual about the position and movement of limbs are damaged, and the patient, because of additional cognitive defects, lacks the capacity to make the necessary observations and inferences to diagnose the paralysis. We discuss the implications of this "discovery" theory and contrast it with other explanations of anosognosia.     

Anosognosia for hemiplegia with pontine infarction

INTRODUCTION: Anosognosia for hemiplegia (AHP) is unawareness of unilateral motor deficit. This syndrome usually is reported in association with large lesions of the nondominant frontal and parietal lobes, the perithalamic lesions or their connexions with cortical or subcortical structures. Little is known about AHP in patients with brainstem's infarctions. CASE REPORT: A 79-year-old right handed woman, without history of intellectual deterioration or psychiatric diseases, with hypertension and paroxysmal atrial fibrillation, was admitted with acute left hemiplegia, somatosensory left deficit and slurred speech. Cerebral MRI indicated a recent infarct in the right anteromedial pontine territory. The patient had moderate anosognosia for hemiplegia (AHP) during the first week after the onset of stroke. There was no sign of left spatial hemineglect or left hemiasomatognosia, no persistant mental confusion and no associated significant cortical or subcortical lesions. CONCLUSION: We presumed that AHP is compatible with brainstem's lesions, particularly with pontine infarcts. The pathogenesis of AHP in pontine infarcts may result from the functional deactivation of frontal and parietal areas.     

On-line anosognosia: unawareness for chorea in real time but not on videotape delay

In hemiplegics, anosognosia (unawareness of deficit) rests on a mismatch between expected and actual movement: a feedback hypothesis emphasizes sensory deficits or neglect, a feedforward hypothesis postulates impaired intention to move. Anosognosia for other problems is less studied. The authors report a man without sensory deficits who was unaware of choreiform movements, except on videotape delay. The authors believe that a feed-forward mechanism underlies his "on-line" unawareness.     

Unawareness after stroke: a review and practical guide to understanding, assessing, and managing anosognosia for hemiplegia

How should stroke patients with poor motor awareness be managed? This question is important because unawareness (or anosognosia) is related to poor rehabilitation and prognosis. This narrative review provides a guide for clinicians and (applied) academics to understanding, assessing and managing anosognosia. Questions addressed are: What is anosognosia? What causes anosognosia? How can anosognosia be assessed? And how can anosognosia be managed? We suggest that anosognosia is a multifaceted disorder, with diverse neuroanatomical and psychopathological origins. Assessment should measure various aspects of awareness, and management should be multidimensional to address problems with motor function, awareness, and emotional/motivational disturbance.     

Anosognosia in very mild Alzheimer's disease but not in mild cognitive impairment

OBJECTIVE: To study awareness of cognitive dysfunction in patients with very mild Alzheimer's disease (AD) and subjects with mild cognitive impairment (MCI). METHODS: A complaint interview covering 13 cognitive domains was administered to 82 AD and 79 MCI patients and their caregivers. The patient groups were comparable according to age and education, and Mini Mental State Examination (MMSE) scores were > or =24 in all cases. The discrepancy between the patients' and caregivers' estimations of impairments was taken as a measure of anosognosia. RESULTS: Self-reports of cognitive difficulties were comparable for AD and MCI patients. However, while in comparison to caregivers MCI patients reported significantly more cognitive impairment (p < 0.05), AD patients complained significantly less cognitive dysfunctions (p < 0.001). CONCLUSIONS: While most MCI patients tend to overestimate cognitive deficits when compared to their caregiver's assessment, AD patients in early stages of disease underestimate cognitive dysfunctions. Anosognosia can thus be regarded as a characteristic symptom at a stage of very mild AD (MMSE > or =24) but not MCI. Accordingly, medical history even in mildly affected patients should always include information from both patient and caregiver.     

The “self-awareness–anosognosia” paradox explained: How can one process be associated with activation of,and damage to,opposite sides of the brain?

Healthy volunteers engaged in self-referential tasks such as reflecting on their personality traits exhibit mostly left lateralized brain activation, yet patients with lack of awareness of their deficit suffer from predominantly right hemisphere damage. How can the same basic process of self-awareness be associated with opposite sides of the brain? Anosognosia and self-awareness substantially differ on important dimensions and thus should not be equated. It is proposed that (1) anosognosia does not actually result from uniquely right hemisphere damage; (2) self-awareness and anosognosia do not constitute unitary concepts and encompass multiple other related processes, most likely associated with activity in distinct anatomical networks; and (3) impaired awareness of deficit is mostly caused by problems with self-monitoring, pre-/post-brain damage comparisons of performance, and episodic memory, and is more passive, unintentional, and about the body. Self-awareness produced by inviting participants to intentionally and actively think about more mental aspects of the self relies on judgements, inferential reasoning, imagination, and semantic memory. Consequently, the “self-awareness–anosognosia” paradox is only apparent. Furthermore, the claim that healthy self-awareness is located in the right hemisphere because anosognosia results from damage to this side of the brain must be fallacious.     

Anosognosia and default mode subnetwork dysfunction in Alzheimer's disease

Research on the neural correlates of anosognosia in Alzheimer's disease varied according to methods and objectives: they compared different measures, used diverse neuroimaging modalities, explored connectivity between brain networks, addressed the role of specific brain regions or tried to give support to theoretical models of unawareness. We used resting‐state fMRI connectivity with two different seed regions and two measures of anosognosia in different patient samples to investigate consistent modifications of default mode subnetworks and we aligned the results with the Cognitive Awareness Model. In a first study, patients and their relatives were presented with the Memory Awareness Rating Scale. Anosognosia was measured as a patient‐relative discrepancy score and connectivity was investigated with a parahippocampal seed. In a second study, anosognosia was measured in patients with brain amyloid (taken as a disease biomarker) by comparing self‐reported rating with memory performance, and connectivity was examined with a hippocampal seed. In both studies, anosognosia was consistently related to disconnection within the medial temporal subsystem of the default mode network, subserving episodic memory processes. Importantly, scores were also related to disconnection between the medial temporal and both the core subsystem (participating to self‐reflection) and the dorsomedial subsystem of the default mode network (the middle temporal gyrus that might subserve a personal database in the second study). We suggest that disparity in connectivity within and between subsystems of the default mode network may reflect impaired functioning of pathways in cognitive models of awareness.     

The anatomy of anosognosia for hemiplegia: a meta-analysis

Anosognosia for hemiplegia is the denial of the contralesional motor deficits that may follow brain damage. Although this disturbance has been reported in the neurological literature since the beginning of the last century, only few longitudinal studies have addressed the issue of the anatomical substrate of the disorder. Here we present a comprehensive review of the literature on anosognosia for hemiplegia from 1938 to 2001, taking into account some of its clinical, epidemiological and anatomical aspects. In particular, an attempt has been made to identify the intra-hemispheric lesion locations most frequently associated to the denial behaviour. Our review shows that anosognosia for hemiplegia most frequently occurs in association to unilateral right-sided or bilateral lesions of different brain areas (cortical and/or subcortical). It seems to be equally frequent when the damage is confined to frontal, parietal or temporal cortical structures, and may also emerge as a consequence of subcortical lesions. Interestingly, the probability of occurrence of anosognosia is highest when the lesion involves parietal and frontal structures in combination, if compared to other combinations of lesioned areas. This pattern of lesions suggests the existence of a complex cortico-subcortical circuit underlying awareness of motor acts that, if damaged, can give raise to the anosognosic symptoms.     

Mnemonic anosognosia in Alzheimer's disease: a test of Agnew and Morris (1998)

Agnew and Morris [Agnew, S. K. & Morris, R. G. (1998). The heterogeneity of anosognosia for memory impairment in Alzheimer's disease: A review of the literature and a proposed model. Aging and Mental Health, 2, 9-15] model of awareness for memory functioning has attempted to account for the variance of anosognosia exhibited within the Alzheimer's disease (AD) population. There has been tentative evidence to suggest that the mnemonic anosognosia sub-type, proposed by this model, is common within the early stages of AD. However, this study is the first directly to test the model. Eighteen older adults with early AD and 18 healthy older adults were recruited. Awareness of memory functioning was monitored using patient-performance measures of "task specific" awareness; a measure of global memory awareness; and a patient-informant measure. The stability of participants' awareness was measured across three word recall lists and after a 20-min delay. Results suggested that, whilst the participants with early AD were less aware of their memory ability than the healthy older adults, they were able to improve their awareness following exposure to a memory task. Furthermore, the improvements in awareness were largely retained after the delay period. These findings are discussed in relation to Agnew and Morris [Agnew, S. K. & Morris, R. G. (1998). The heterogeneity of anosognosia for memory impairment in Alzheimer's disease: A review of the literature and a proposed model. Aging and Mental Health, 2, 9-15] model of mnemonic anosognosia and to current thinking about autobiographical memory.     

Transient insight induction with electroconvulsive therapy in a patient with refractory schizophrenia: a case report and systematic literature review

Anosognosia or lack of illness awareness is a clinical manifestation of both schizophrenia and right hemispheric lesions associated with stroke, neurodegeneration, or traumatic brain injury. It is thought to result from right hemispheric dysfunction or interhemispheric disequilibrium, which provides a neuroanatomical model for illness unawareness in schizophrenia. Lack of insight contributes to medication nonadherence and poor treatment outcomes and is often refractory to pharmacological and psychological interventions. We present the first report of transient illness awareness (<8 hours) after individual bilateral electroconvulsive therapy treatments in the case of a 39-year-old man with antipsychotic refractory schizophrenia. Electroencephalography demonstrated frontal slow wave activity with shifting frontotemporal predominance, which was concurrent with the patient's transient level of insight. A systematic review of the literature on electroconvulsive therapy-induced illness awareness in schizophrenia and psychotic disorders produced zero relevant results. Future research should focus on the prospective role of focal interventions, such as transcranial magnetic stimulation, in the development of a neurophysiological model for anosognosia reversal in schizophrenia that may, in turn, contribute to novel therapeutic developments targeting lack of illness awareness.     

A diagnostic formulation for anosognosia in Alzheimer's disease

Objective

To determine the earliest symptoms of anosognosia in people with Alzheimer''s disease and to validate a criteria‐guided strategy to diagnose anosognosia in dementia.

Methods

A consecutive series of 750 patients with very mild or probable Alzheimer''s disease attending a memory clinic, as well as their respective care givers, was assessed using a comprehensive psychiatric evaluation.

Results

The factors of anosognosia for (1) basic activities of daily living (bADL), (2) instrumental activities of daily living (iADL), (3) depression and (4) disinhibition were produced by a principal component analysis on the differential scores (ie, caregiver score minus patient score) on the anosognosia questionnaire for dementia. A discrepancy of two or more points in the anosognosia‐iADL factor was found to have a high sensitivity and specificity to identify clinically diagnosed anosognosia in people with Alzheimer''s disease. By logistic regression analysis, the severity of dementia and apathy were both shown to be noticeably associated with anosognosia in people with Alzheimer''s disease.

Conclusion

Anosognosia in those with Alzheimer''s disease is manifested as poor awareness of deficits in iADL and bADL, depressive changes and behavioural disinhibition. The frequency of anosognosia is found to increase considerably with the severity of dementia. The validity of a specific set of criteria to diagnose anosognosia in people with Alzheimer''s disease was shown, which may contribute to the early identification of this condition.Anosognosia (from the Greek “nosos” (illness) and “gnosis” (knowledge)) is a term coined by Babinski to refer to the phenomenon of denial of hemiplegia.¹ From an etymological perspective, the term anosognosia may be construed as the lack of knowledge or awareness of an illness. Anosognosia has also been reported among patients with Wernicke''s aphasia, who do not attempt to correct paraphasias and who may become irritable with others when their jargon‐loaded speech is not properly understood. Anton''s syndrome occurs in patients with cortical blindness, who deny being blind and confabulate responses when asked to recognise visually presented objects. In the context of people with Alzheimer''s disease, anosognosia was construed as the denial or lack of awareness of impairments in activities of daily living (ADL) or about neuropsychological deficits.^2,3 Different strategies have been used to assess anosognosia in Alzheimer''s disease, and these are briefly described as follows (see Clare^4,5 for a thorough review).