Theory of mind in frontal and temporal lobe epilepsy: cognitive and neural aspects.

PURPOSE: Theory of mind (ToM) is an important prerequisite to social behavior. This study evaluated ToM in patients with temporal (TLE) or frontal lobe epilepsy (FLE) aiming to determine the cognitive aspects, severity, and pathophysiologic mechanisms of ToM impairment in focal epilepsy. METHODS: One hundred thirty-eight patients with TLE (n = 109) or FLE (n = 29) and 69 healthy subjects underwent the Faux Pas task (FPT), which evaluates the recognition and comprehension of others' mental states, and neuropsychological tests for other cognitive functions. KEY FINDINGS: Factor analysis of all test scores yielded two ToM factors (Recognizing faux pas, FP; Excluding nonexistent FP) distinct from the Control, Language, Matching, and Praxis factors. With respect to healthy subjects, both TLE and FLE patients showed correct exclusion of nonexistent FPs but significantly lower recognition and comprehension of real FPs. FLE patients were also impaired with respect to TLE patients. In the whole patient group, schooling and group membership predicted ToM impairment. In FLE patients, the comprehension of mental states was predicted by disease duration, whereas TLE patients' comprehension of affects and intentions was associated with early age of seizure onset and medial temporal lobe sclerosis (MTLS). SIGNIFICANCE: Focal epilepsy impairs advanced ToM abilities. FLE may affect online performances owing to long-lasting dysfunctions of the prefrontal areas. MTLS may provoke selective ToM deficits due to medial temporal damage, prefrontal dysfunctions, or early interference with cognitive development. Future studies are needed to determine the implications of ToM impairment on behavior and quality of life.

The neuropsychological pattern of Unverricht-Lundborg disease.

This study determined the neuropsychological pattern of Unverricht-Lundborg disease (ULD) and its relationship to disease-related variables. Twenty-one ULD patients were evaluated using neuropsychological tests for abstract reasoning, attention, planning, set-shifting, theory of mind, visual perception, visuomotor coordination, ideomotor, orofacial and constructive praxis, language, learning, and memory. The control groups consisted of 21 healthy subjects and 21 patients with cryptogenic temporal lobe epilepsy (TLE). Multivariate analysis of variance showed that, in comparison with both control groups, the ULD patients showed significantly impaired abstract reasoning, attention, planning, word fluency, constructive praxis, and visuospatial memory and learning. Factor analysis of the test scores obtained by the ULD and TLE groups identified four factors (processing and execution, praxis, memory, theory of mind), and separate ANOVAs using epilepsy-related and demographic variables as covariates showed that the ULD patients had significantly impaired processing and execution. Correlation and regression analyses showed that processing and execution was significantly associated with diagnosis, disease duration and education, and logistic regression analyses indicated that it significantly predicted a diagnosis of ULD. To conclude, ULD is characterised by impaired processing and execution functions. This impairment is a strong independent predictor of ULD and may contribute to the characterisation of the diagnosis.

The neuropsychological and neuroradiological correlates of slowly progressive visual agnosia.

The case of a 64-year-old woman affected by slowly progressive visual agnosia is reported aiming to describe specific cognitive-brain relationships. Longitudinal clinical and neuropsychological assessment, combined with magnetic resonance imaging (MRI), spectroscopy, and positron emission tomography (PET) were used. Sequential neuropsychological evaluations performed during a period of 9 years since disease onset showed the appearance of apperceptive and associative visual agnosia, alexia without agraphia, agraphia, finger agnosia, and prosopoagnosia, but excluded dementia. MRI showed moderate diffuse cortical atrophy, with predominant atrophy in the left posterior cortical areas (temporal, parietal, and lateral occipital cortical gyri). 18FDG-PET showed marked bilateral posterior cortical hypometabolism; proton magnetic resonance spectroscopic imaging disclosed severe focal N-acetyl-aspartate depletion in the left temporoparietal and lateral occipital cortical areas. In conclusion, selective metabolic alterations and neuronal loss in the left temporoparietooccipital cortex may determine progressive visual agnosia in the absence of dementia.

Atypical frontotemporal dementia as a new clinical phenotype of Gerstmann-Straussler-Scheinker disease with the PrP-P102L mutation. Description of a previously unreported Italian family.

OBJECTIVE: To describe a new dementia phenotype of Gerstmann-Straussler-Scheinker disease (GSS) in a previously unreported Italian family. Design Longitudinal clinical and neuropsychological assessment, combined with magnetic resonance imaging (MRI), single positron emission tomography (SPECT) and molecular genetic studies. Setting Neuropsychology Laboratory, and Division of Neuropathology and Neurology, "C. Besta" National Neurological Institute. Patients and participants Three members of the family. Measurements and results. Standardised neuropsychological tests were used to determine cognitive patterns. The proband had a history of primary dementia characterised by loss of initiative, planning, behaviour control, awareness, language and memory; the two relatives suffered from progressive ataxia. MRI of the demented patient revealed brain atrophy with a hyperintense signal in the frontal cortex; SPECT revealed decreased perfusion in the left temporal and parietal cortex and left thalamus. The two ataxic patients showed cerebellar atrophy with no signs of altered perfusion. Analysis of the PRNP gene showed a proline/leucine substitution at codon 102 in all three patients, associated with methionine/valine heterozygosity at the polymorphic codon 129. Conclusions Primary dementia with prominent frontotemporal signs is a new phenotypical expression of P102L-related GSS that coexists in the same family with the ataxic form of the disease. This remarkable variability suggests that still unidentified genetic or acquired factors may modulate the manifestations of GSS. Genetic examination of the PRNP should be included in the diagnostic work-up of patients with poorly classifiable dementia.

Differential neuropsychological patterns of frontal variant frontotemporal dementia and Alzheimer's disease in a study of diagnostic concordance.

Although the pathological hallmarks of Alzheimer's disease (AD) and frontal variant frontotemporal dementia (fvFTD) predict different cognitive patterns, many comparative neuropsychological studies showed no difference in the expected cognitive domains. Inconsistencies in diagnostic criteria, small cohorts of patients, and neuropsychological assessment may account for such findings. Moreover, discrepancies in memory and executive dysfunctions that are expected to distinguish AD and fvFTD may reflect the basic brain organization. Adhering to a strict concordance of clinical and neuroradiological criteria, we compared many patients with AD and fvFTD using a large neuropsychological battery. One hundred and thirty-nine patients with AD (n=89) or fvFTD (n=50) were retrospectively considered in order to verify the diagnostic congruence of clinical and neuroradiological aspects. On this basis, 117 patients with AD (n=77) or fvFTD (n=40) with similar duration and severity of dementia were selected. Ninety-one healthy subjects were also controlled. Mean scores in tests for abstract reasoning, planning, set shifting, initiative, verbal fluency, immediate and episodic memory, constructive, ideomotor and orofacial praxis, selective and divided attention, visuomotor coordination, and visual perception were evaluated. Separate analyses of variance and post hoc Bonferroni tests showed that, with respect to controls, both patient groups were significantly impaired in all neuropsychological tests. Compared to fvFTD patients, AD patients were significantly impaired in episodic memory, selective attention, visual perception, visuomotor coordination, and constructive praxis, whereas no differences were found in executive, intellective, and linguistic abilities between the two patient groups. Logistic regression analyses revealed that episodic memory significantly predicted the diagnosis of AD while no executive deficit was able to predict the diagnosis of fvFTD. To conclude, memory, attention, and visuoconstructive deficits may distinguish AD with respect to fvFTD, in accordance with the severe temporo-parietal-occipital degeneration characterizing AD, but no executive impairment is consistently able to identify a relative compromise in fvFTD. Executive functions impairments possibly reflect the altered spatial-temporal integration of the frontal lobes with different brain areas, which prevents a clear-cut cognitive-brain correlation.

Processing of syntactically complex sentences relies on verbal short-term memory: evidence from a short-term memory patient.

The role of the phonological loop in auditory sentence comprehension was examined in a 35-year-old woman with a selective deficit of verbal short-term memory (STM). More specifically, the objective of the experiment was to test whether sentence comprehension is limited by number of propositions, as suggested by Rochon, Waters, and Caplan (2000), or whether it depends on syntactic complexity. In an offline task, severe impairment was present on cleft objects and centre-embedded structures; the deficit on object relatives in right peripheral position was less relevant, and the patient was able to handle sentential coordination easily. In an online task, her processing of centre-embedded structures and object relatives in right peripheral position was significantly slower than that in controls. She was also significantly slower in processing the verb of the object relative in centre-embedded structures. The results obtained do not support the claim that the difficulties encountered by patients with limited working-memory resources are due to the number of propositions in the sentence; they do, however, suggest a direct involvement of the phonological loop in processing syntactically complex sentences.

The comprehension of ambiguous idioms in aphasic patients.

The ability to understand ambiguous idioms was assessed in 15 aphasic patients with preserved comprehension at a single word level. A string-to-word matching task was used. Patients were requested to choose one among four alternatives: a word associated with the figurative meaning of the idiom string; a word semantically associate with the last constituent of the idiom string; and two unrelated words. The results showed that patients' performance was impaired with respect to a group of matched controls, with patients showing a frontal and/or temporal lesion being the most impaired. A significant number of semantically associate errors were produced, suggesting an impairment of inhibition mechanisms and/or of recognition/activation of the idiomatic meaning.