ناتوانی در ادراک بیماری و الگوهای اختلال خود آگاهی مشاهده شده در عملکرد بالینی

Abstract Disturbances of self-awareness are observed in a wide variety of patients. While group studies can provide useful information concerning potential mechanisms underlying these complex disturbances, experienced clinicians, such as Babinski, recognized the potential value of repeated observations on individual patients to insure the reliability of findings and to aid in diagnosis. This paper describes patterns of impaired self-awareness (ISA) that are observed in clinical practice that suggest a model for clinical classification. Repeated observations are reported on four patients ranging from anosognosia for hemiplegia (AHP), ISA associated with bilateral cerebral dysfunction with frontal lobe involvement, and apparent denial of disability (DD). A patient who presents with denial of ability (DA) is also studied for comparison purposes. When coupled with brain imaging findings, the nature of the patients' subjective responses to feedback regarding their functional capacities, speed of finger tapping in the left, nondominant hand, and their capacity to express and perceive affect suggests different clinical correlates in these four conditions.

. Introduction In June of 1914, Felix Babinski gave us the term “anosognosia” (Bisiach & Geminiani, 1991), although many agree that the lack of self-perception of neurological deficits was described by such clinicians as Gabriel Anton and Arnold Pick before the term came into existence (Prigatano & Schacter, 1991). Over the last 100 years, numerous clinical and experimental observations have been reported regarding anosognosia, particularly anosognosia for hemiplegia (AHP) after stroke (e.g., Garbarini et al., 2012, Jenkinson et al., 2009, Morin et al., 2003, Orfei et al., 2007, Vocat and Vuilleumier, 2010 and Vocat et al., 2013). It has become progressively clear that while AHP is a striking phenomenon that still attracts considerable neuroscientific attention, disturbances in self-awareness can be observed in a wide variety of neurological and psychiatric patients (Prigatano, 2009 and Prigatano, 2010). They include post-acute patients with severe traumatic brain injury (TBI) (Prigatano and Altman, 1990 and Sherer et al., 1998), multiple sclerosis (MS) (Prigatano, Hendin, & Heiserman, 2014), Parkinson's disease (Maier, et al., 2012), dementia of the Alzheimer's type (Salmon et al., 2006), mild cognitive impairment of the amnestic type (Ries et al., 2007), and frontotemporal dementia (Miller et al., 2001). This clinical reality has to be kept in mind when developing theoretical models for explaining anosognosia and related phenomena. A second clinical reality is that while anosognosia is a direct effect of brain dysfunction (Bisiach & Geminiani, 1991) often reflecting cortical lesions (Fotopoulou et al., 2010 and Prigatano, 2010) not all disturbances in self-awareness in brain dysfunctional patients necessarily represent a neuropsychological disturbance (Weinstein & Kahn, 1955). Denial and repression, as psychological methods of coping, may also contribute to their altered subjective perceptions (and verbalizations) about their functional capacity (Prigatano and Weinstein, 1996 and Thibierge and Morin, 2013). This has prompted a more detailed analysis of the relationship of anosognosia to mood states (Mograbi & Morris, 2014) as well as exploration of the various correlates of implicit awareness in anosognosia (Fotopoulou et al., 2010 and Mograbi and Morris, 2013). Present-day studies of anosognosia and related phenomena may be enhanced by case reports that reveal different types of disturbances in self-awareness observed in clinical practice. Correlates of improved self-awareness of neurological and neuropsychological disturbances, as well as the correlates of persistent and worsening impaired self-awareness (ISA) may provide further insights as to underlying mechanisms responsible for these complex disturbances. 1.1. Psychological and neurological (neuropsychological) perspectives when evaluating patients with ISA Between October of 1885 and the end of February, 1886, Sigmund Freud studied with Charcot at the Salpêtrière in Paris. During this time, Babinski was Charcot's Chief Resident. Reportedly, Freud and Babinski both examined a patient together and presented their findings to Charcot. Freud reported that the relationship with Babinski was cordial, but not especially warm. It has also been noted that Freud's name did not appear in any of Babinski's publications (Philippon & Poirier, 2009, pg. 314). While there has been an effort to study psychoanalytic concepts/constructs using the methods of present-day neuroscience (Carhart-Harris and Friston, 2010, Fotopoulou et al., 2012, Shevrin et al., 2002, Solms and Turnbull, 2002 and Thibierge and Morin, 2013), necessary clinical details are often lacking when interpreting the behavior of individual anosognostic patients. The well-recognized report by Ramachandran (1994) highlights the problem. Ramachandran (1994) described in a clinical vignette fashion verbalizations of a 76-year-old woman who presented with AHP. Her comments were classical for this condition, and repeated similar earlier (more detailed) observations by Sandifer (1946). He then described a second patient, a 79-year-old woman with AHP, and reported her responses to questions after undergoing a caloric stimulation test, known to briefly eliminate neglect and anosognosia (Ronchi et al., 2013). Immediately after the stimulation, the patient reported that her left hand/arm was paralyzed. Several hours later, when the effect has worn off, the patient reverted back to describing herself as having no difficulties with her left hand and arm. Ramachandran (1994) then provided the following verbatim accounts: “Examiner: This morning, two doctors did something to you. Do you remember? Patient: Yes. They put water in my ear; it was very cold. Examiner: Do you remember they asked some questions about your arms, and you gave them an answer? Do you remember what you said? Patient: No, what did I say? Examiner: What do you think you said? Try and remember. Patient: I said my arms were okay.” (pg. 323–324) Ramachandran interpreted the patient's response as indicating that the patient, at some level, had a much deeper knowledge of her paralysis than her earlier verbalizations indicated. He evoked the concept of repression to explain her behavior. It would have also been helpful to ask the patient when she said that she had previously said her arm was okay, whether or not she believed that to be true. Was the patient simply reporting what she remembered, or was she reporting what she experiences/believed in the present? Furthermore, detailed description of how the patient dealt with anxiety-provoking events in her life may have been of some help to clarify whether or not repression/denial contributed to her verbalizations about her disability. In typical scientific publications, such detailed clinical analysis is often not presented since case reports are thought to be limited in the knowledge they provide. In the spirit of Babinski who believed in the importance of repeated clinical observations on individual patients in order to determine the reliability of a given phenomenon, four cases are presented. While they differ in their diagnoses, they share the common feature of showing a disturbance of self awareness of either a neurological or neuropsychological function. Their verbal (subjective) responses to questions asked about their functional capacities were studied and compared. Their emotional responses to questions and to neuropsychological testing procedures were recorded. Their ability to generate affect in their tone of voice, perceive facial affect, and demonstrate spontaneous affect were tested since these emotional features may be impaired in anosognosia (Heilman & Harciarek, 2010). Speed of finger tapping, using the Halstead Finger Tapping Test (HFTT) was also measured in each patient. This task distinguishes TBI patients with ISA from those without this disturbance (Long et al., 2014 and Prigatano and Altman, 1990). It has also been shown to be associated with ISA in Parkinson patients (Maier et al., 2012) and a patient with MS (Prigatano et al., 2014).

3. Results 3.1. Case 1: anosognosia following a right cerebral hemisphere stroke Case 1 is that of a 51-year-old woman who presented with AHP following a large intracranial bleed of a right parietal AVM (Prigatano, Matthes, Hill, Wolf, & Heiserman, 2011). She also suffered infarctions of both posterior cerebral arteries which resulted in cortical blindness. By the time she underwent a neuropsychological evaluation (20 days post onset), she was aware of her blindness, but not her hemiplegia (measured by Bisiach's Scale of Anosognosia) (for a detailed description of her MRI findings as well as her pattern of recovery over the first year following her stroke see Prigatano et al., 2011). While undergoing rehabilitation, she did not report any motor limitations. She participated in all therapies as requested. She understood questions asked of her, but did demonstrate mild verbal learning and memory difficulties several months post CVA. She also present with left sided neglect. She never spoke in disparaging terms about her clinical condition or her need to be in the hospital. As she became aware of her blindness, she showed expected anxiety over her visual impairments. Prior to her neurological illness, she was independent in all activities of daily living. She worked for a state agency and had very favorable job evaluations. There was no history of pre-existing psychiatric disturbance. Her recovery from AHP occurred precisely when she could move the index finger of the left, affected hand for the first time when performing the HFTT (Prigatano et al., 2011). Interestingly, her right hand speed of finger tapping was below normal limits when first tested (i.e., 20 days after her vascular accident) but improved just before she could tap for the first time with her affected, left hand (see Table 1). Table 1. Neuropsychological findings for a patient with AHP. Post CVA with initial anosognosia for hemiplegia and severe neglect Examination #1 Examination #2 Examination #3 Examination #4 Examination #5 Examination #6 April 2009 May 2009 June 2009 Dec. 2009 March 2010 Nov. 2013 1 month post (before AHP resolves) 2 months post (after AHP resolves) 3 months post 6 months post 1 year post 4 years, 9 months post Age 51 Age 51 Age 51 Age 52 Age 52 Age 56 HFTT (raw scores)a RH 36 46 48.4 40.8 47 37 LH 0 19 25.2 22.2 23 16.7 PCRS (raw scores) Patient N/A N/A N/A N/A 75 99 Significant other N/A N/A N/A 110 108 95 Clinician's rating scale (raw scores) ISA N/A N/A N/A N/A N/A 0/10 DD N/A N/A N/A N/A N/A 0/10 BNIS affect subtest Able to generate affect in tone of voice N/A N/A Yes Yes Yes Yes Response to a fearful/surprised face N/A N/A “Sad” “Sad” “No emotion” “Can't see” Shows spontaneous affect N/A N/A No No No “Can't see” N/A refers to not administered. a Raw scores are presented to reflect what is clinically observed. For a right-handed female in her age range, speed of finger tapping is typically in the high 40s per 10 sec. About a 10% slower speed is typically observed in the nondominant hand. Speeds decrease with normal aging. Table options After her AHP resolved and her neglect improved, she could easily generate affect in her tone of voice. Her visual perception of affect could not be reliability tested because of her visual impairments. Unfortunately, her ability to generate affect in her tone of voice during the time of her AHP was not tested (see Table 1). She was followed carefully for the first year post onset of her neurological condition and then followed intermittently for an additional three years, nine months. Once her AHP resolved, she showed normal sadness and worry over her motor and visual impairments. She never denied or minimized her neurological or neuropsychological disturbances. Given her clinical state and inability to read due to her cortical blindness, she was not asked to complete the PCRS during the early stages of her recovery. At one year post onset, the PCRS was read to her and her description of her functional limitations matched clinical observation very closely. She, perhaps, was more realistic about her limitations than her sister at the time as the sister wanted to be positive and encouraging. At nearly 5 years post onset, both the patient and her sister who cared for her were realistic about her functional limitations. Ratings obtained on the CRS at that time revealed no behavioral indications of ISA and DD. Thus, once her AHP resolved, there was no evidence of residual impaired awareness or psychological denial. Her functional limitations remained severe and were compatible with typical clinical outcomes for this patient group (Jehkonen, Ahonen, Dastidar, Laippala, & Vilkki, 2000). 3.2. Case 2: ISA of cognitive deficits in a patient with MS Case 2 is that of a 55-year-old woman with a 20-year history of relapsing-remitting MS who was seen for a neuropsychological examination because others reported a decline in her cognitive status. The patient had previously been a successful administrator for a state agency. There was no history of psychiatric illness. She lived with a partner for many years and the relationship continued despite her declining condition. It became progressively clear she was having cognitive difficulties suggestive of “executive dysfunction” as commonly occurs in MS patients (Arnett et al., 1994 and Smith and Arnett, 2010). Job supervisors progressively brought concerns regarding her performance to her attention. While initially responsive to those concerns, she slowly demonstrated a certain indifference to their feedback. Eventually she was asked to leave her position. She showed frustration over their decision, but beyond that no obvious emotional reaction. When interviewed, the patient reported no decline in her cognitive functioning and had no explanation for why her supervisors felt that, with the passage of time, her work became unacceptable. She was told by supervisors that her written reports were tangential, lengthy, and unclear in their conclusions. When presented with this information, the patient showed a mild perplexity with no affective reaction. She made a comment to the effect that “maybe something is wrong, but I don't see it.” Her partner was very concerned about the patient's declining functioning and noted the patient seemed to develop her indifference and lack of insight slowly over the three years preceding her present evaluation. The partner felt the patient may have sensed some possible decline in her work skills earlier in the progression of her disease, but noted now she reported none. On formal neuropsychological testing, her intelligence was within the normal range and memory scores were compatible with IQ estimates. On tests thought to sample “executive functioning” (the FAS verbal fluency task, Trail Making Test-Parts A and B, and the Wisconsin Card Sorting Test), her performance was decidedly abnormal (see Prigatano et al., 2014 for further details). Her HFFT score was normal in her right, dominant hand, but was below normal limits in the left, nondominant hand. Her level of slowness in the left hand was compatible with previous group findings with TBI patients who demonstrated ISA (Prigatano & Altman, 1990). On the BNIS Affect subtest, the patient had difficulty generating affect in her tone of voice and with perceiving facial affect. She described, for example, a fearful or surprised face as “neutral.” She showed no spontaneous smiling when shown an incongruent stimulus designed to provoke laughter. On the PCRS, she overestimated her functional capacities compared to her partner's ratings. On the CRS, her affective reactions were highly consistent with ISA, but not DD (see Table 2). Table 2. Neuropsychological examination findings for a patient with ISA. MS 20+ year history of relapsing-remitting Examination #1 March 2013 Examination #2 October 2013 Age 55 Age 56 HFTT (raw scores)a RH 44.2 42.4 LH 34.8 33.4 PCRS (raw scores) Patient 126 117 Significant other 116 Not available Clinician's rating scale (raw scores) ISA 9/10 9/10 DD No 9/10 No 8/10 BNIS affect subtest Able to generate affect in tone of voice No No Response to a fearful/surprised face “Neutral” “Neutral” Shows spontaneous affect No No a Average speed of finger tapping in the left hand is often 35 taps or slower in persons who show ISA after severe TBI (Prigatano & Altman, 1990). Table options MRI of the brain revealed generalized volume loss, including global loss of white matter volume, thinning of the corpus callosum, and prominence of cerebral sulci. She also demonstrated bi-frontal neuronal and white matter volume loss with the right frontal regions showing the greatest volume loss (Prigatano et al., 2011). 3.3. Case 3: apparent ISA and DD for cognitive and behavioral disturbances after severe TBI At age 26, a young man suffered a severe TBI (admitting Glasgow Coma Scale score = 6) while working in construction. MRI scans of the brain seven years post trauma revealed bilateral cerebral volume loss, particularly involving the right parietal-temporal regions as well as encephalomalacia of both frontal lobes and volume loss in both cerebellar hemispheres. His clinical presentation was complicated. When first evaluated 6 months post injury, he underreported his symptoms/impairments and appeared perplexed when given feedback regarding the severity of his neuropsychological difficulties. With further discussion, he scoffed at the findings and dismissed any impairments as either being insignificant or pre-existing (i.e., prior to his accident). As time progressed, he became delusional, arguing he was able to go back to his previous job, but was held back by others. He believed the doctors were simply making money by continuing treatment and evaluations and that potential employers were prejudiced against him because he had a history of TBI. His neuropsychological test findings revealed severe impairments in memory and information processing speed, with a general reduction in overall intelligence (over a 25-year period his IQ scores ranged between 72 and 77). On the HFTT, the patient was bilaterally slow in speed of finger tapping and showed ataxic movement in the right, dominant hand. While he learned to write with his left hand after his accident, left hand speed of finger tapping was compromised over a 25-year period of time. On the PCRS, he repeatedly reported greater competency than his mother reported. On the CRS, he repeatedly demonstrated behavioral signs of both ISA and DD, but ISA seemed more pronounced (Table 3). Table 3. Neuropsychological examination findings for a patient with ISA and DD. TBI DOI = February 1988 Examination #1 Examination #2 Examination #3 Examination #4 Examination #5 Sept. 1988 May 1991 May 1993 July 2006 Oct. 2013 Age 26 Age 29 Age 31 Age 44 Age 51 HFTT (raw scores) RH 21 19 19 19 22 LH 36 39 42 40 35 PCRS (raw scores) Patient 130 128 143 138 136 Significant other 112 106 85 84 99 Clinician's rating scale (raw scores) ISA N/A N/A N/A Yes 8/10a Yes 7/10 DD N/A N/A N/A Yes 6/10a Yes 5/10 BNIS affect subtest Able to generate affect in tone of voice N/A N/A Can't do happy – No Yes Yes Response to a fearful/surprised face N/A N/A Puzzled Anger: “Confident” Happy: “Something on her mind” Fear: “Shout” Anger: “Doesn't understand” Happy: “Happy” Fear/Surprise: “Confused” Shows spontaneous affect N/A N/A No No No a Retrospective ratings. Table options On the BNIS Affect subtest, the patient initially had difficulties generating affect in his tone of voice, but with time could do so. On numerous occasions, however, he had difficulty perceiving a fearful or surprised face, initially calling it “puzzled” and later “confused.” He showed no spontaneous affect on any of the testing occasions when presented with stimuli intended to evoke a smile or laugher. 3.4. Case 4: DA: self reports of severe memory impairment in the face of normal memory performance A thirty-nine year old right-handed female reported to her physician a decline in her memory. Despite these complaints, she was successfully working as businesswomen. MRI of the brain, as well as neurological and medical evaluation, failed to reveal any abnormality that could account for her reported cognitive difficulties. Repeat neuropsychological testing over six years demonstrated average intelligence with normal verbal and nonverbal memory capacities. On the HFTT, her speed of finger tapping scores were repeatedly normal bilaterally. On the BNIS Affect subtest, she repeatedly could not generate the tone of happiness when asked to read a sentence out loud. She was accurate in perceiving facial affect during her second and third examination. She always demonstrated spontaneous affect (i.e., a smile) when shown a humorous picture (Table 4). Table 4. Neuropsychological examination findings for a patient with “denial of ability”. Subjective memory complaints with perception of progressive decline Examination #1 Examination #2 Examination #3 November 2007 January 2009 September 2013 Age 39 Age 41 Age 45 HFTT (raw scores) RH 41.3 N/A 43.6 LH 42.2 N/A 43.8 PCRS (raw scores) Patient 119 N/A 115 Significant other 121 N/A N/A Clinician's rating scale (raw scores) ISA N/A N/A N/A DD N/A N/A N/A BNIS affect subtest Able to generate affect in tone of voice Can't do happy No Yes Can't do happy No Response to a fearful/surprised face “Confused” “Fear” “Surprise” Shows spontaneous affect Yes Yes No Table options On the PCRS, she did not over-report her behavioral competencies, but limited data were obtained using the PCRS-R form. The CRS was not administered since she was not reporting a lack of cognitive symptoms, but rather the presence of worsening cognitive symptoms. Detailed discussions revealed a history of sexual abuse during childhood. The patient considered its possible a role in her symptoms, but elected not to seek out psychotherapy. A similar pattern was observed when she was examined approximately two years later. During her third examination, the patient acknowledged that sexual abuse issues might be influencing her, but it was simply too emotionally overwhelming for her to talk about these issues. She spontaneously stated she wanted to keep thoughts of the abuse out of her awareness. Abbass (2005) has noted that in many forms of somatization disorder “isolation of affect” and repression are observed. Memory complaints are common is this patient group. 3.5. Comparison of the four cases The first three cases had unequivocal brain disorders. Their MRI brain scans revealed different patterns of findings compatible with their diagnoses, but each of the patients had right cerebral hemisphere damage. Each of these patients showed abnormal speed of finger tapping in the left nondominant hand as measured by the HFTT. The one patient who had no signs of an underlying brain disorder had normal speeds of finger tapping in both the right and left hands. These observations were repeatedly documented. When AHP resolved, Case 1 showed no restriction in generating affect in her tone of voice. Case 2, who presented with progressively worsening ISA, repeatedly could not do this task successfully. In contrast a patient with ISA and DD (Case 3) could do the task most of the time. Most strikingly, however, was the observation that the last two patients could not successfully perceive facial affect. The patient with DA of memory function (Case 4) could easily do this task. There also was an important difference in the quality of responses when these patients attempted to generate happy and then angry tones of voice. In the case of severe developing ISA (Case 2) there was a lack of vocal prosody on both attempts. In the case of DA (Case 4), in which depression appeared to be a prime feature, the patient verbalized “I can't do happy.” On two out of three examinations she could not generate anger in her tone of voice. It is also noteworthy that when presented with visual stimuli aimed at provoking a smile or laughter, Cases 2 and 3 showed no reaction. Case 4 did (on two of the three examination periods). Case 1 could not be tested using these stimuli because of her cortical blindness. Once AHP resolved, Case 1 appeared to be very realistic about her daily functional capacities (as measured by the PCRS). In contrast, both patients with persistent ISA (Cases 2 and 3) repeatedly over-estimated their functional capacities compared to significant others' reports. There was, however, a clear difference on the CRS ratings for Cases 2 and 3. Case 2 was essentially “neutral” in her emotional reactions with no behavioral indications of DD in the presence of severe ISA, while Case 3 had many negative emotional reactions as well as behavioral indicators on ISA. Where these different types of reactions represent differences in underlying brain pathology between the two cases or the presence of psychologically based denial remains undetermined, but the findings are compatible with the notion that both “organic unawareness” and “psychological denial” may exist in a given patient. Finally, it should be noted that Case 4's ratings on the PCRS were comparable to her husband's ratings. This patient seemed realistic in her daily functional capacities, but reported memory deficits that could not be detected with serial neuropsychological examination findings.