Emergence of hyper empathy after right amygdalohippocampectomy.

We report a fascinating case of a patient with a hyper empathy that appeared after resective epilepsy surgery. This behavioral modification has remained unchanged since the surgery took place 13 years ago. Recent neuropsychological objective assessments confirmed hyper empathy in a self-report questionnaire, and revealed higher affective theory of mind than controls in a "Reading the Mind in the Eyes Task." Temporal lobe epilepsy is the most common form of epilepsy and the investigation of emotional processes after surgery in these patients deserves to be related.

Conversion, dissociative amnesia, and Ganser syndrome in a case of "chameleon" syndrome: anatomo-functional findings.

The term "chameleon" was first used in the seventeenth century by Sydenham to describe a patient with a protean semiology. We report a single case of "chameleon" syndrome that challenges the current international criteria for somatoform disorders, dissociative amnesia, and Ganser syndrome. The florid symptoms were as follows: anterograde and retrograde amnesia (including semantic, episodic, and procedural deficits), loss of identity, atypical neuropsychological impairment (approximate answers), left sensitive and motor deficit, and left pseudochoreoathetosis movement disorders. Additional behavioral disorders included the following: anxiety, clouded consciousness, hallucinations, and "belle indifference". A single photon emission computed tomography examination showed bilateral temporal, frontal and a right caudate (in the head of the caudate nucleus) hypoperfusion concordant with a common mechanism of repression in these disorders.

Beauty and Paintings: Aesthetic Experience in Patients with Behavioral Variant Frontotemporal Dementia When Viewing Abstract and Concrete Paintings.

We assessed the aesthetic experience of patients with behavioral variant frontotemporal dementia (bvFTD) to understand their ability to experience feelings of the sublime and to be moved when viewing paintings. We exposed patients with bvFTD and control participants to concrete and abstract paintings and asked them how moved they were by these paintings and whether the latter were beautiful or ugly. Patients with bvFTD declared being less moved than control participants by both abstract and concrete paintings. No significant differences were observed between abstract and concrete paintings in both patients with bvFTD and control participants. Patients with bvFTD provided fewer "beautiful" and more "ugly" responses than controls for both abstract and concrete paintings. No significant differences in terms of "beautiful" and "ugly" responses were observed between abstract and concrete paintings in both patients with bvFTD and control participants. These findings suggest disturbances in the basic affective experience of patients with bvFTD when they are exposed to paintings, as well as a bias in their ability to judge the aesthetic quality of paintings.

Brain plasticity in the motor network is correlated with disease progression in amyotrophic lateral sclerosis.

OBJECTIVE: To test the influence of functional cerebral reorganization in amyotrophic lateral sclerosis (ALS) on disease progression. METHODS: Nineteen predominantly right-handed ALS patients and 21 controls underwent clinical evaluation, functional Magnetic Resonance Imaging (fMRI), and diffusion tensor imaging. Patients were clinically re-evaluated 1 year later and followed until death. For fMRI, subjects executed and imagined a simple hand-motor task. Between-group comparisons were performed, and correlations were searched with motor deficit arm Medical Research Council (MRC) score, disease progression ALS Functional Rating Scale (ALSFRS), and survival time. RESULTS: By the MRC score, the hand strength was lowered by 12% in the ALS group predominating on the right side in accordance with an abnormal fractional anisotropy (FA) limited to the left corticospinal tract (37.3% reduction vs. controls P < 0.01). Compared to controls, patients displayed overactivations in the controlateral parietal (P < 0.004) and somatosensory (P < 0.004) cortex and in the ipsilateral parietal (P < 0.01) and somatosensory (P < 0.01) cortex to right-hand movement. Movement imagination gave similar results while no difference occurred with left-hand tasks. Stepwise regression analysis corrected for multiple comparisons showed that controlateral parietal activity was inversely correlated with disease progression (R(2) = 0.43, P = 0.001) and ipsilateral somatosensory activations with the severity of the right-arm deficit (R(2) = 0.48, P = 0.001). CONCLUSIONS: Cortical Blood Oxygen Level Dependent (BOLD) signal changes occur in the brain of ALS patients during a simple hand-motor task when the motor deficit is still moderate. It is correlated with the rate of disease progression suggesting that brain functional rearrangement in ALS may have prognostic implications.

Impaired emotional processing in a patient with a left posterior insula-SII lesion.

The present case-report investigated the influence of a lesion in the left posterior insula-SII cortices on the processing of emotions. MB and 16 normal controls explicitly rated the valence and the intensity of both facial expressions and emotional words. In addition, they had to perform a number comparison task and a lexical decision task without focusing their attention on emotional components of stimuli. MB identified the valence of emotional words as well as the control group. Nevertheless, she provided higher intensity scores for disgusted words and her responses in the lexical decision task were significantly delayed for these stimuli. In addition, MB's response times were not differently influenced by the presence of irrelevant emotional faces. However, she explicitly identified fewer facial expressions of disgust and she assessed them as significantly less intense. This pattern of results contributes to highlight the psychological and behavioral disorders observed after a left posterior insular stroke.

Fear recognition impairment in early-stage Alzheimer's disease: when focusing on the eyes region improves performance.

A decline in the ability to identify fearful expression has been frequently reported in patients with Alzheimer's disease (AD). In patients with severe destruction of the bilateral amygdala, similar difficulties have been reduced by using an explicit visual exploration strategy focusing on gaze. The current study assessed the possibility of applying a similar strategy in AD patients to improve fear recognition. It also assessed the possibility of improving fear recognition when a visual exploration strategy induced AD patients to process the eyes region. Seventeen patients with mild AD and 34 healthy subjects (17 young adults and 17 older adults) performed a classical task of emotional identification of faces expressing happiness, anger, and fear in two conditions: The face appeared progressively from the eyes region to the periphery (eyes region condition) or it appeared as a whole (global condition). Specific impairment in identifying a fearful expression was shown in AD patients compared with older adult controls during the global condition. Fear expression recognition was significantly improved in AD patients during the eyes region condition, in which they performed similarly to older adult controls. Our results suggest that using a different strategy of face exploration, starting first with processing of the eyes region, may compensate for a fear recognition deficit in AD patients. Findings suggest that a part of this deficit could be related to visuo-perceptual impairments. Additionally, these findings suggest that the decline of fearful face recognition reported in both normal aging and in AD may result from impairment of non-amygdalar processing in both groups and impairment of amygdalar-dependent processing in AD.

Phenotype and imaging features associated with APP duplications.

BACKGROUND: APP duplication is a rare genetic cause of Alzheimer disease and cerebral amyloid angiopathy (CAA). We aimed to evaluate the phenotypes of APP duplications carriers. METHODS: Clinical, radiological, and neuropathological features of 43 APP duplication carriers from 24 French families were retrospectively analyzed, and MRI features and cerebrospinal fluid (CSF) biomarkers were compared to 40 APP-negative CAA controls. RESULTS: Major neurocognitive disorders were found in 90.2% symptomatic APP duplication carriers, with prominent behavioral impairment in 9.7%. Symptomatic intracerebral hemorrhages were reported in 29.2% and seizures in 51.2%. CSF Aß42 levels were abnormal in 18/19 patients and 14/19 patients fulfilled MRI radiological criteria for CAA, while only 5 displayed no hemorrhagic features. We found no correlation between CAA radiological signs and duplication size. Compared to CAA controls, APP duplication carriers showed less disseminated cortical superficial siderosis (0% vs 37.5%, p = 0.004 adjusted for the delay between symptoms onset and MRI). Deep microbleeds were found in two APP duplication carriers. In addition to neurofibrillary tangles and senile plaques, CAA was diffuse and severe with thickening of leptomeningeal vessels in all 9 autopsies. Lewy bodies were found in substantia nigra, locus coeruleus, and cortical structures of 2/9 patients, and one presented vascular amyloid deposits in basal ganglia. DISCUSSION: Phenotypes associated with APP duplications were heterogeneous with different clinical presentations including dementia, hemorrhage, and seizure and different radiological presentations, even within families. No apparent correlation with duplication size was found. Amyloid burden was severe and widely extended to cerebral vessels as suggested by hemorrhagic features on MRI and neuropathological data, making APP duplication an interesting model of CAA.

Perceived eye region and the processing of fearful expressions in mild cognitive impairment patients.

BACKGROUND: The aim of the present study was to assess the possibility of compensating early facial expression recognition impairments in amnestic Mild Cognitive Impairment (a-MCI) patients. METHODS: Twelve patients with a-MCI and 17 healthy participants matched according to age and education participated in the study. The originality of the present study was to cue the recognition of facial expressions (happiness, anger, fear, and neutral) by comparing eye region expressions and entire facial expressions. RESULTS: A deficit in the recognition of fearful expressions was observed in a-MCI patients relative to the control group, whereas recognition of all the other emotional expressions was spared. Nevertheless, when eye expressions cued the recognition of fearful facial expressions, the performance of normal controls and a-MCI patients was comparable. CONCLUSION: The present paper indicates a selective impairment in fear recognition in the prodromal state of Alzheimer's disease, and the possibility of compensating this deficit by orienting selective attention on specific facial features.

Prospective evaluation of behavioral scales in the behavioral variant of frontotemporal dementia.

BACKGROUND: The Neuropsychiatric Inventory (NPI) and the Frontal Behavioral Inventory (FBI) are widely used in patients with the behavioral variant of frontotemporal dementia (bvFTD). Yet, few data are available on the long-term relevance of these scales. MATERIAL AND METHODS: Based on a bvFTD population that participated in the Memantine Clinical Trial (NCT00200538), we studied the evolution and correlation between scores obtained on behavioral scales (NPI and FBI), cognitive scales [Mini-Mental State Examination (MMSE) and Mattis Dementia Rating Scale (MDRS)] and a burden scale [Zarit Burden Inventory (ZBI)]. The assessments were performed at 1 year in 41 patients and at 2 years in 23 patients who agreed to participate in this open-label study. RESULTS: The 2-year scores obtained on the FBI were significantly higher than the scores at inclusion while those obtained on the NPI did not change. There were significant correlations between the FBI, and the MDRS and MMSE, especially regarding the negative items. The ZBI correlated with behavioral scales at all stages for positive items. CONCLUSIONS: This study based on a large population shows that the FBI is a better tool than the NPI for the long-term assessment of bvFTD patients. Moreover, the FBI allows a distinction to be made between behavioral disturbances that involve cognitive functions from those which have an important impact on caregiver burden.

Cognitive Impairment in Secondary Progressive Multiple Sclerosis: Effect of Disease Duration, Age, and Progressive Phenotype.

BACKGROUND: Cognitive deficits are common in multiple sclerosis (MS) and affect patients at all stages of the disease, regardless of phenotype. AIMS: This literature review focuses the cognitive deficits observed in secondary progressive MS (SPMS). It is mainly based on studies that compared the frequency and main characteristics of cognitive deficits in SPMS with other phenotypes. METHODS: A bibliographic search was carried out using the PubMed database with the following keywords: multiple sclerosis, secondary-progressive, cognition. RESULTS: Thirteen studies were initially selected that were published in English, reporting the neuropsychological data of a sample of at least 30 patients with SPMS, comparing them with patients with other phenotypes. Studies suggest that there is an association between the duration of the disease and the frequency and extent of the cognitive disorders. Studies also showed that the SP form is associated with an increased frequency of cognitive impairment and with an increased severity as compared to relapsing-remitting MS (RRMS). Compared to RRMS, progressive forms of MS are associated with more severe impairment in certain cognitive areas, such as episodic verbal memory, information processing speed, working memory, or verbal fluency. Two studies showed that cognitive performances decline overtime in SPMS. CONCLUSION: Cognitive disorders are more frequent and more severe in the SP form than in relapsing course of MS. The profile of cognitive impairment encountered in the SP form also appears to be different from those found in the other phenotypes.

Explicit and implicit emotional processing modifications in pharmacoresistant left temporal lobe epilepsy and anxiodepressive disorders.

We examined whether anxiodepressive patients with left temporal lobe epilepsy could be differentiated from those with depression but without epilepsy on tasks that investigate attentional bias toward and explicit judgment of emotional stimuli. Eight depressive patients, eight anxiodepressive patients with epilepsy, and eight controls participated in the present study. Anxiodepressive with epilepsy and depressive patients had comparable depression scores and the same cognitive profile. Two distinct emotional tasks were used: the decision lexical task and the number comparison task. Three emotional connotations were presented: neutral, positive, and negative. The pattern of results showed an attentional bias toward negative words and pictures in depressive patients and only toward negative words in anxiodepressive patients with epilepsy. Moreover, depressive patients explicitly judged negative stimuli with lower intensity and anxiodepressive patients judged neutral stimuli with higher intensity. The present study specifies the emotional functioning in depression with or without left temporal lobe epilepsy.

How emotional pictures influence visuospatial binding in short-term memory in ageing and Alzheimer's disease?

The present study examines the prediction that emotion can facilitate short-term memory. Nevertheless, emotion also recruits attention to process information, thereby disrupting short-term memory when tasks involve high attentional resources. In this way, we aimed to determine whether there is a differential influence of emotional information on short-term memory in ageing and Alzheimer's disease (AD). Fourteen patients with mild AD, 14 healthy older participants (NC), and 14 younger adults (YA) performed two tasks. In the first task, involving visual short-term memory, participants were asked to remember a picture among four different pictures (negative or neutral) following a brief delay. The second task, a binding memory task, required the recognition by participants of a picture according to its spatial location. The attentional cost involved was higher than for the first task. The pattern of results showed that visual memory performance was better for negative stimuli than for neutral ones, irrespective of the group. In contrast, binding memory performance was essentially poorer for the location of negative pictures in the NC group, and for the location of both negative and neutral stimuli in the AD group, in comparison to the YA group. Taken together, these results show that emotion has beneficial effects on visual short-term memory in ageing and AD. In contrast, emotion does not improve their performances in the binding condition.

Can maintaining cognitive function at 65 years old predict successful ageing 6 years later? The PROOF study.

BACKGROUND: preservation of cognitive abilities is required to have a good quality of life. The predictive value of cognitive functioning at 65 years old on successful ageing 6 years later is not established. METHODS: nine hundred and seventy-six questionnaires were sent by mail to a sample of healthy and voluntary French pensioners. Successful ageing was defined through health status and well-being. Cognitive abilities had been assessed 6 years earlier according to an objective method (Free and Cued Selective Recall Reminding Test (FCSRT), the Benton visual retention test and the similarities subtest of the Wechsler Adult Intelligence Scale-Revised) and a subjective one (Goldberg's anxiety scale, Mac Nair's scale and a Visual Analogue Scale to evaluate memory abilities change in the last 5 years). RESULTS: six hundred and eighty-six questionnaires could be analysed. The mean age was 72.9 ± 1.2 years old with 59% of women and 99% lived at home. Well-being was negatively correlated with the FCSRT (r = -0.08, P = 0.0318) but positively related with the Benton (r = 0.09, P = 0.0125) and the similarities tests (r = 0.09, P = 0.0118). There is a negative correlation between anxious and cognitive complaints measured at baseline, and successful ageing indicators 6 years later. CONCLUSION: preservation of cognitive abilities at the age of retirement can predict a successful ageing 6 years later. ClinicalTrials.gov Identifier: NCT00759304.

Improving the Diagnosis of the Frontal Variant of Alzheimer's Disease with the DAPHNE Scale.

BACKGROUND: The frontal variant of Alzheimer's disease (fAD) is poorly understood and poorly defined. The diagnosis remains challenging. The main differential diagnosis is the behavioral variant of frontotemporal degeneration (bvFTD). For fAD, there is some dissociation between the clinical frontal presentation and imaging and neuropathological studies, which do not always find a specific involvement of the frontal lobes. DAPHNE is a behavioral scale, which demonstrated excellent performance to distinguish between bvFTD and AD. OBJECTIVE: The aim of the present study was to assess the reliability of this new tool to improve the clinical diagnosis of fAD. METHODS: Twenty fAD patients and their caregivers were prospectively included and were compared with 36 bvFTD and 22 AD patients. RESULTS: The three main behavioral disorders in the fAD patients were apathy, loss of empathy, and disinhibition. Three disorders were discriminant because they were less frequent and less severe in the fAD patients than in the bvFTD patients, namely hyperorality, neglect, and perseverations. This specific pattern of behavioral disorders was corroborated by SPECT or 18FDG PET-CT scan that showed that patients with fAD could have a medial frontal hypoperfusion, whereas in bvFTD patients the orbitofrontal cortex was the main involved region, with more diffuse hypoperfusion. CONCLUSION: We demonstrated that DAPHNE had good sensitivity and good specificity to discriminate between the three groups and in particular between fAD and bvFTD patients. DAPHNE is a quick tool that could help clinicians in memory clinics not only to differentiate bvFTD from typical AD but also from fAD.

Cognitive function and sleep related breathing disorders in a healthy elderly population: the SYNAPSE study.

STUDY OBJECTIVES: Sleep related breathing disorders (SRBD) are risk factors for cognitive dysfunction in middle-aged subjects, but this association has not been observed in the elderly. We assess the impact of SRBD on cognitive performance in a large cohort of healthy elderly subjects. DESIGN: Cross-sectional study examining the association between subjective memory test, neuropsychological battery testing and SRBD in the elderly. SETTING: Community-based sample in home and research clinical settings. PARTICIPANTS: 827 subjects, 58.5% women, aged 68 y at study entry, participated in the study. All were free of previously diagnosed SRBD, coronary heart disease, and neurological disorders, including stroke and dementia. Clinical interview, neurological assessment, polygraphy, and extensive cognitive testing were conducted for all participants. INTERVENTION: N/A. MEASUREMENT AND RESULTS: SRBD (apnea-hypopnea index [AHI] > 15 events/h) was diagnosed in 445 (53%) subjects, 167 (37%) of them with AHI > 30. Minimal daytime sleepiness was found in the group; 9.2% of the population had an Epworth Sleepiness Scale score > 10. No significant association was found between AHI, nocturnal hypoxemia, and cognitive scores. Comparison of mild vs severe cases showed a trend toward lower cognitive scores with AHI > 30, affecting delayed recall and Stroop test. CONCLUSIONS: The impact of undiagnosed SRBD on cognitive function appeared quite limited in a generally older healthy population, and only slightly affected severe cases. The implication of undiagnosed SRBD on the cognitive impairment in elderly subjects remains hypothetical and needs to be prospectively studied.

TARDBP mutations in motoneuron disease with frontotemporal lobar degeneration.

TDP-43 (TAR-DNA binding protein) aggregates in neuronal inclusions in motoneuron disease (MND), as well as in frontotemporal lobar degeneration (FTLD) and FTLD associated with MND (FTLD-MND). Mutations in TARDBP gene, coding for TDP-43, were found in patients with pure MND. We now describe TARDBP mutations in two patients with FTLD-MND, presenting with a behavioral variant of FTLD and semantic dementia, suggesting that TDP-43 may also have a direct pathogenic role in FTLD disorders.

The Wechsler Digit Symbol Substitution Test as the best indicator of the risk of impaired driving in Alzheimer disease and normal aging.

AIMS: Our purpose was to identify cognitive tools associated with unsafe driving among elderly drivers of varying cognitive levels. METHODS: Twenty drivers with early-stage dementia of the Alzheimer type and 56 nondemented drivers aged 65-85 were recruited. Various cognitive processes were measured and unsafe driving was evaluated during an in-traffic road test with 3 different indicators and a composite indicator. RESULTS: The Wechsler Digit Symbol Substitution Test score was the best cognitive measure to detect unsafe drivers using the composite driving indicator. CONCLUSION: The Digit Symbol Substitution Test may be used by physicians for the evaluation and follow-up of older patients, with or without Alzheimer-type dementia, as a screening tool of unsafe driving.

A clinical screening tool for objective and subjective cognitive disorders in multiple sclerosis.

BACKGROUND: Cognitive dysfunction is common in multiple sclerosis (MS). Deficits can affect attention, concentration, planning, and memory. They can have severe functional consequences in many domains. Cognitive complaints are frequently associated with other confounding factors (fatigue, anxiety, depression, or treatment side effects). In most cases, cognitive assessment is proposed after a spontaneous complaint, but determining the extent of discomfort perceived by the patient, the influence of coexisting factors, or the optimal timing for a more complete neuropsychological assessment is difficult. OBJECTIVE: The objective of this work was to evaluate the feasibility and relevance of a fast global assessment of both objective and subjective cognitive dysfunction in MS. METHODS: MS patients underwent a brief cognitive assessment including 7 visual analogue scales (VASs) asking about the patient's subjective level of discomfort in various domains, a memory test (Barbizet's lion story), a commonly used test of information processing speed (Symbol Digit Modalities Test [SDMT]) and self-reporting questionnaires for fatigue and mood (Fatigue Severity Scale [FSS] and Hospital Anxiety and Depression Scale [HADS]). Spearman correlation coefficients among scores were estimated. RESULTS: The mean age of the 73 patients included was 48.3 (SD 11.1) years; 78% were females and 52.8% had the remittent-recurrent MS form, 8.3% the primary progressive form, and 38.9% the secondary progressive form. In less than 20min, this brief cognitive assessment was able to identify symptoms and quantify discomfort level. Symptoms of fatigue and anxiety frequently coexisted with cognitive complaints. We found modest correlations between scores on the VAS fatigue and the FSS and between scores on the VAS mood and the HADS. Analytical evaluation revealed that most patients had similar SDMT and recall profiles; however, a small proportion showed a dissociation between these 2 tests, which validated the inclusion of both tests in the assessment. Accounting for coexisting factors (e.g., anxiety and fatigue) and their functional repercussions is essential for prioritizing these problems within the context of multidisciplinary patient treatment. CONCLUSION: Considering the possible multifactorial character of cognitive dysfunction in MS, it is essential to ask patients about their experiences and to take into account cognitive complaints in the follow-up of patients. The assessment tool we propose is simple and easy to use in a clinical setting and provides the information necessary for requesting (or not) a more complete neuropsychological assessment.

Partial deletion of the MAPT gene: a novel mechanism of FTDP-17.

A heterozygous genomic deletion removing exons 6 to 9 of the microtubule associated protein tau (MAPT) gene, predicting to result into a truncated protein lacking the first microtubule binding domain, was detected in a patient with frontotemporal dementia (FTD). Cell culture experiments showed that the truncated tau isoforms had a dramatic decrease in the normal binding to microtubules but acquired the ability to bind microtubule associated protein-1B (MAP-1B). This indicates that this tauopathy likely results both from a loss of function mechanism and from a deleterious gain of function by which cytoplasmic deleted forms of tau sequester another MAP. Both mechanisms could contribute to impair microtubule dynamics.

Implicit sensitivity to disgust-inducing stimuli in self-neglect FTD patients.

BACKGROUND: Among behavioral and socioemotional changes occurring before cognitive decline at the early stages of frontotemporal dementia, the patients often manifest with self-neglect and some criteria of Diogene syndrome. Despite the lack of accurate behavior regarding disgust, are they still sensitive to the emotional content of disgust-inducing words or scenes? METHODS: Eleven patients with frontotemporal dementia, 11 healthy controls, and 34 young adults performed a lexical decision task, where some of the words conveyed an emotional content and a number comparison task while they were presented with emotion-inducing pictures. They were not instructed to identify the emotional content of the words and pictures. RESULTS: Contrary to the healthy controls paired for age, the patients provided delayed responses for disgust-inducing words in the lexical decision task and in presence of disgust-inducing pictures in the number comparison task. CONCLUSIONS: Although they manifest with self-neglect and inaccurate behavior regarding dirt, the patients were still sensitive to disgust, provided that this sensitivity was tested implicitly, suggesting that they above all suffer from inabilities in matching the appropriate social behavior with such emotions.