Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia: An MRI Study of 16 French Cases.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia is an autosomal dominant leukoencephalopathy related to CSF1R gene mutations. A growing number of clinicoradiologic phenotypes have been described. In this study, we analyzed brain imaging findings in 16 patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia to refine radiologic diagnostic clues. T2/FLAIR white matter hyperintensities were present in all patients with frontal or frontoparietal predilection, with asymmetric distribution in more than one-third. Brain atrophy and callosal involvement were almost constant, and corticospinal tract involvement was frequent. Moreover, deep white matter hyperintense dots on DWI and deep punctate calcifications on CT were often found. Conversely, deep gray matter nuclei, external capsules, and brain stem were rarely involved. Our series emphasized the great variability of MR imaging findings seen in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia. A complete imaging screening including DWI, T2*, and CT is mandatory to accurately assess patients with suspected inherited adult-onset leukoencephalopathy.

Gestural apraxia.

Gestural apraxia was first described in 1905 by Hugo Karl Liepmann. While his description is still used, the actual terms are often confusing. The cognitive approach using models proposes thinking of the condition in terms of production and conceptual knowledge. The underlying cognitive processes are still being debated, as are also the optimal ways to assess them. Several neuroimaging studies have revealed the involvement of a left-lateralized frontoparietal network, with preferential activation of the superior parietal lobe, intraparietal sulcus and inferior parietal cortex. The presence of apraxia after a stroke is prevalent, and the incidence is sufficient to propose rehabilitation.

Discrepancy between social and nonsocial decision-making under uncertainty following prefrontal lobe damage: the impact of an interactionist approach.

Deficits in decision-making are thought to contribute significantly to socio-behavioral impairments of patients with frontal lobe damage. The purpose of this study was to test the hypothesis of whether the inappropriate social behavior of patients with frontal lesions can be viewed as the product of a general failure of decision-making ability or as the result of socio-cognitive impairment. We studied a group of patients with prefrontal lesions (FL patients, n = 15) and a group of matched healthy controls (n = 30) on the Iowa Gambling task (IGT) of nonsocial decision-making, environmental dependency phenomena (EDP) during social interaction, and the "reading the mind in the eyes" and "character intention task" of theory of mind (TOM) tasks. The FL patients were impaired in both TOM and EDP protocols but, surprisingly, they behaved appropriately in the IGT. In addition, FL patients with EDP did not differ in executive functioning, IGT and TOM measures from those who did not demonstrate these behavioral disorders. The right orbitofrontal cortex was associated with social decision-making deficits. By adopting an interactionist approach, this study raises the possibility of identifying components of social and nonsocial decision-making, which could be helpful in understanding the behavioral disorders of FL patients.

Executive functions in clinical and preclinical Alzheimer's disease.

Executive functions is an umbrella term describing a wide range of higher order processes that allow the flexible modification of thought and behaviour in response to changing cognitive or environmental contexts. Impairment of executive functions is common in neurodegenerative disorders such as Alzheimer's disease. These deficits negatively affect everyday activities and hamper the ability to cope with other cognitive or behavioural disorders. In this paper, we propose a synthesis of the knowledge on executive impairments in clinical and preclinical Alzheimer's disease, mostly leaning on the current studies made in this domain. We made some propositions for neuropsychological assessment of executive functions in preclinical and clinical phases of Alzheimer's disease. We hope that this overview will provide a useful insight into an area that is still insufficiently explored in the field of the neuropsychology of Alzheimer's disease.

Post-acute assessment programme for patients with traumatic brain injury: measuring the gap between patients' expectations on entering and end of programme recommendations.

OBJECTIVE: To compare the expectations of patients with brain injury (TBI) entering a post-acute programme to the recommendations made at the end. DESIGN: Retrospective study (1997 and 2009). INTERVENTION: This 12-week post-acute programme included ecological multidisciplinary assessment of physical and cognitive disabilities, independence in activities of daily living and work abilities. Recommendations made at the conclusion of the programme included advice regarding the ability to work in an unsheltered or a sheltered environment and possible social activities. RESULTS: Two hundred and forty patients participated. The main objective of 95.8% was return-to-work: 93.7% expected a normal work environment, 2.1% considered a sheltered environment and 4% entered the programme with the aim of improving social abilities and integration in the community. The recommendations included return-to-work in 68.3% of cases, in an unsheltered environment in 44.2% and in a sheltered environment in 24.1% and advice for contact with social services in order to achieve better social integration in 31.7%. There was a discrepancy between expectations and recommendations in half of the cases. CONCLUSION: The discrepancy between patients' expectations and recommendations is in part due to the cognitive disorders; long-term rehabilitation programmes should focus on this issue.

[The new 2011 recommendations of the National Institute on Aging and the Alzheimer's Association on diagnostic guidelines for Alzheimer's disease: Preclinal stages, mild cognitive impairment, and dementia]. / Les nouvelles recommandations 2011 du National Institute on Aging et de l'Alzheimer's Association sur le diagnostic de la maladie d'Alzheimer : stades précliniques, mild cognitive impairment et démence.

BACKGROUND: Criteria for the clinical diagnosis of Alzheimer's disease (AD) were established in 1984, and they needed to be updated and revised, in vue of the scientific knowledge acquired over the last decades. METHODS: The National Institute on Aging (NIA) and the Alzheimer's Association (AA) sponsored a series of advisory round table meetings to establish a revision of diagnostic and research criteria for AD. The workgroups reviewed the biomarker, epidemiological, and neuropsychological evidence, and proposed conceptual frameworks as well as operational research criteria based on the prevailing scientific evidence to date. RESULTS: Three preclinical stages of AD were proposed: asymptomatic amyloidosis, asymptomatic amyloidosis+neurodegeneration, amyloidosis+neurodegeneration+subtle cognitive decline. The preclinical workgroup developed recommendations to determine the factors, which best predict the risk of progression from normal cognition to mild cognitive impairment (MCI) and AD dementia. It is necessary to refine these models with longitudinal clinical research studies. The workgroups on MCI and AD dementia sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. The symptomatic predementia phase of AD was referred to as MCI due to AD. Core clinical and cognitive criteria of MCI were proposed, the final set of criteria for MCI due to AD has four levels of certainty, depending on the presence and nature of the biomarker findings. Criteria for all-cause dementia and for AD dementia were presented. Dementia caused by AD were classified in: probable AD dementia, possible AD dementia, and probable or possible AD dementia with evidence of the AD pathophysiological process, for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis. CONCLUSIONS: In the revised criteria, a conceptual distinction is made between AD pathophysiological processes and clinically observable syndromes. The core clinical criteria of the recommendations regarding MCI due to AD and AD dementia are intended to guide diagnosis in the clinical setting whereas the recommendations of the preclinical AD workgroup are intended purely for research purposes and do not have any clinical implications. Considerable work is needed to validate the criteria that use biomarkers and to standardize biomarker analysis for use in community settings.

High frequency of potentially pathogenic SORL1 mutations in autosomal dominant early-onset Alzheimer disease.

Performing exome sequencing in 14 autosomal dominant early-onset Alzheimer disease (ADEOAD) index cases without mutation on known genes (amyloid precursor protein (APP), presenilin1 (PSEN1) and presenilin2 (PSEN2)), we found that in five patients, the SORL1 gene harbored unknown nonsense (n=1) or missense (n=4) mutations. These mutations were not retrieved in 1500 controls of same ethnic origin. In a replication sample, including 15 ADEOAD cases, 2 unknown non-synonymous mutations (1 missense, 1 nonsense) were retrieved, thus yielding to a total of 7/29 unknown mutations in the combined sample. Using in silico predictions, we conclude that these seven private mutations are likely to have a pathogenic effect. SORL1 encodes the Sortilin-related receptor LR11/SorLA, a protein involved in the control of amyloid beta peptide production. Our results suggest that besides the involvement of the APP and PSEN genes, further genetic heterogeneity, involving another gene of the same pathway is present in ADEOAD.

[Alzheimer's disease and visual impairment]. / Les troubles visuels au cours de la maladie d'Alzheimer.

Alzheimer disease is the most prevalent cause of cognitive decline in older adults. The typical presentation of Alzheimer disease is memory dysfunction, however, presentations with impairment in other domains may occur. Visual symptoms may be the first manifestation of Alzheimer disease. The purpose of this article is to review the spectrum of visual system disturbances found in Alzheimer disease.

A contribution to the study of environmental dependency phenomena: the social hypothesis.

Environmental dependency phenomena refer to the symptoms initially described by Lhermitte (1983, 1984) under the terms of "utilization behavior" and "imitation behavior". These clinical signs are linked to essential notions such as free-will and human autonomy, and seem to be specific of the frontal pathology. Surprisingly, few studies have addressed these symptoms and inconsistent definitions are available. To investigate the theoretical and clinical definitions of environmental dependency phenomena, three groups of neurological patients (n=60) with frontal, subcortical, and posterior brain lesions were compared. Clinically, our findings help to rehabilitate the definitions of Lhermitte (1983, 1984) and challenge the classical interpretation in terms of an executive control deficit. The frontal specificity of the disorders and the lack of relation between executive/behavioral deficits were supported. The right orbitofrontal cortex seems particularly involved in environmental dependency. These results offer some evidences for differentiate two historical concepts of neuropsychology, namely the "frontal" and "dysexecutive" syndromes. A new interpretation of environmental dependency phenomena is provided which could be helpful to orient the neuropsychology of frontal syndrome.

Utilization behavior: clinical and theoretical approaches.

Lhermitte (1983) coined the term "utilization behavior" (UB) to define a neurobehavioral syndrome in which the visuo-tactile presentation of objects compels patients to grasp and use them, despite the fact that they have not been instructed to do so. The author suggested that UB was the consequence of frontal lobe damage. Thereafter, Shallice, Burgess, Schon, and Baxter (1989) questioned Lhermitte's (1983) procedure for eliciting UB, putting forward an alternative research methodology that led to differentiate two forms of UB: "induced" and "incidental." To date, there has been no direct comparison between these two procedures, nor have any other methodologies been used to explore this clinical sign, which is related to fundamental concepts such as free will and human autonomy. We investigated UB in 70 subjects (25 patients with frontal lobe lesions, 10 patients with posterior brain damage and 35 control subjects) using the methodologies of Lhermitte (1983) and Shallice et al. (1989), as well as an original "verbal generation" procedure. Our results show that the verbal generation procedure reveals UB efficiently and that elicitation of this sign appears to be directly linked to the content of the task. We discuss the interpretation of UB in terms of an executive control deficit.

[A study of action planning in patients with Alzheimer's disease using the zoo map test]. / Etude de la planification de l'action au moyen du test du plan du zoo dans la maladie d'Alzheimer.

INTRODUCTION: Executive dysfunction is regularly reported in patients with Alzheimer's disease. Nevertheless few studies have focused on planning ability in this neurodegenerative disease. OBJECTIVES: This study aimed to investigate the formulation and the execution of plans in Alzheimer's disease using an ecological planning subtask derived from the Behavioural Assessment of the Dysexecutive Syndrome test battery, the "Zoo Map Test". There are two trials. The first trial consists of a "high demand" version of the subtask in which the subjects must plan in advance the order in which they will visit designated locations in a zoo (formulation level). In the second, or "low demand" version, the subject is simply required to follow a concrete externally imposed strategy to reach the locations to visit (execution level). The test was given to 16 patients with Alzheimer's disease and 13 normal elderly subjects. RESULTS: The two way ANOVAs mainly showed more difficulties in patients with Alzheimer's disease than in healthy elderly in both conditions. The difference between formulation and execution was greater in patients with Alzheimer's disease than in healthy elderly. Planning impairments mainly correlated with behavioural changes (in particular motivational changes) observed by patient's relatives. CONCLUSION: These results suggest that patients with Alzheimer's disease have some problems to mentally develop logical strategies and to execute complex predetermined plans, which are partially related to behavioural changes.

What about theory of mind after severe brain injury?

BACKGROUND: Behavioural changes are often reported after a severe traumatic brain injury (TBI). These changes are usually a greater burden for relatives than physical or cognitive impairments. This study investigated social cognition in TBI patients using two theory of mind (TOM) tasks. METHOD: The performances of 17 patients with severe TBI and 17 matched controls were compared on two tasks designed to investigate understanding of other people's mental states: The 'Reading the Mind in the Eyes' test (RME) and the 'Character Intention Task' (CIT). TBI patients and controls were also given several executive function tasks. RESULTS: Compared to healthy controls, patients were impaired in most executive tests and in both TOM tasks. No relationship was found between TOM and executive measures. This is consistent with Rowe's position, who suggested an independence between executive functioning and social cognition. These data suggest that TBI patients may have specific social intelligence disturbances. CONCLUSION: Future work should employ additional tests of TOM and behavioural ratings and recruit more patients in order to complete analysis.

Two clinicopathological cases of a dominantly inherited, adult onset orthochromatic leucodystrophy.

Leucodystrophies of orthochromatic type are a heterogeneous group that occur mainly in childhood and have no known enzyme deficiency. We report here the clinicopathological features of a new family of orthochromatic leucodystrophy with three main characteristics: a probably autosomal dominant inheritance; two phenotypes based on age of onset; and very few abnormalities of white matter on MRI findings in one case. The first patient, aged 58 years, had frontal dementia and epilepsy; the second, aged 38 years, had motor signs and dementia, but no epilepsy. The histopathological features of our two cases were leucodystrophy of orthochromatic subtype. However, the radiological features (MRI and mostly FLAIR sequences) of the first case did not suggest leucodystrophy.

Acute delirium, delusion, and depression during IFN-beta-1a therapy for multiple sclerosis: a case report.

Adverse effects of interferon (IFN) treatment are common, and efforts to minimize these reactions are of considerable importance. IFN-beta-1a is an established therapy for patients with relapsing-remitting multiple sclerosis (MS). Its psychiatric side effects are debated and not yet fully established. The authors report here the case of a patient on IFN-beta-1a therapy for MS who developed acute delirium, delusion, and depression that ceased with treatment discontinuation. Although he had a history of recurrent major depressive disorder, his prior psychiatric illness had followed a course that was clinically independent of other signs of MS. This observation points out psychiatric vulnerability of patients taking IFN-beta-1a therapy for MS and suggests that IFN-beta-1a may induce or exacerbate preexisting psychotic symptoms.

A case study of selective impairment of the central executive component of working memory after a focal frontal lobe damage.

RC is a 36-year-old man who sustained a closed head injury with bilateral frontal lobe hypometabolism in 1978. In 1994, after a lobectomy of a large part of the left frontal lobe, he presented no behavioral disruption and normal performances on most of intelligence, long-term memory, and executive tests. However, he showed deficits in tasks that implicate short-term storage (i.e., span tasks). These deficits in working memory were explored with regard to Baddeley's model using computerized tasks. On these tasks RC showed normal functioning of the articulatory loops and dysfunction of the central executive component in dual tasks. These results confirm those reported in another single case study by Van Der Linden, Coyette, and Seron (1992) and indicate that dual-task performance may assess one separable feature of executive functions.

Influence of centrality and distinctiveness of actions on script sorting and ordering in patients with frontal lobe lesions.

In order to further investigate script knowledge in patients with frontal lobe lesions (FP), 30 participants with frontal brain damage, 14 controls with posterior brain damage (PC) and 30 normal controls (NC) were asked to sort script actions with various degrees of centrality and distinctiveness according to the script to which they belonged and their order of execution. Actions were given in 3 conditions: scripts with headers (SH), scripts without headers (SwH) and scripts with distractor header (SDH). Results confirmed the dual dissociation we observed in a previous study (Allain, Le Gall, Etcharry-Bouyx, Aubin, & Emile, 1999). Twelve FP made numerous errors in sequencing actions regardless of the conditions, but rejected the irrelevant title. Fourteen FP made few sequencing errors but used the irrelevant title. The last 4 FP performed as well as the PC and NC in every condition. Sorting errors made by the FP mainly concerned actions with low levels of centrality and distinctiveness. These data are consistent with the view that frontal lobe lesions selectively impair the syntactic component of script representation without affecting its semantic component.

[Incidence of grasping and its relationship to cerebral lesions]. / Comportement de grasping: incidence clinique et corrélations anatomo-cliniques.

Grasping is associated with frontal lobe pathology. Nevertheless, there is lack of precise anatomical correlations and very few studies are published. The aim of the study was to determine the incidence of the grasping and its relationship to cerebral lesions. We studied 236 patients admitted to the Neurology Department (108 women and 128 men; mean age 65.3), and tested with a standardized procedure (De Renzi and Barbieri, 1992). A score of grasping was determined for each patient. The locations of the cerebral lesions were assessed by two neurologists using the method of Damasio and Damasio (1989). Grasping was found in 38 patients (16.1p.100) with dementia or cerebral damage. In all cases, the lesion affected the frontal lobe. The patients with grasping showed a significant higher number of lesioned areas particularly for the frontal and the parietal regions. The score of right grasping was significantly higher with a lesion in the right paraventricular frontal and in the left parietal paraventricular areas. The score of left grasping was significantly higher with a lesion in the left frontal paraventricular area. These results are discussed in relationship with motor control.

[Design of a force sensor to evaluate the grasping movement]. / Développement d'un capteur de force pour l'analyse du comportement de grasping.

Grasping phenomena are abnormal motor behaviours described after cerebral lesions. They are defined as a stereotyped response, consisting of a progressive forced closure of the patient's hand on the examiner's fingers, when they are slowly moved exerting a strong pressure across the palm in an upward direction. Several types are described. The aim of the study was to develop a force sensor to evaluate the force of grasping in accordance with the force of dragging. The characteristics of this force sensor are presented and the clinical application in two selected patients demonstrated.