Anna Rita Giovagnoli

A Recessive Mutation in the APP Gene with Dominant-Negative Effect on Amyloidogenesis

β-Amyloid precursor protein (APP) mutations cause familial Alzheimers disease with nearly complete penetrance. We found an APP mutation [alanine-673→valine-673 (A673V)] that causes disease only in the homozygous state, whereas heterozygous carriers were unaffected, consistent with a recessive Mendelian trait of inheritance. The A673V mutation affected APP processing, resulting in enhanced β-amyloid (Aβ) production and formation of amyloid fibrils in vitro. Co-incubation of mutated and wild-type peptides conferred instability on Aβ aggregates and inhibited amyloidogenesis and neurotoxicity. The highly amyloidogenic effect of the A673V mutation in the homozygous state and its anti-amyloidogenic effect in the heterozygous state account for the autosomal recessive pattern of inheritance and have implications for genetic screening and the potential treatment of Alzheimers disease.

Learning and Memory Impairment in Patients with Temporal Lobe Epilepsy: Relation to the Presence, Type, and Location of Brain Lesion

Summary: Purpose: To study the influence of epileptogenic lesions on learning and memory alterations in patients with temporal lobe epilepsy (TLE).

Self-reporting of everyday memory in patients with epilepsy: relation to neuropsychological, clinical, pathological and treatment factors

Patients with epilepsy frequently complain of memory problems, but neuropsychological tests sometimes fail to detect consistent deficits; this may be because laboratory tests are poor indicators of everyday memory problems, or because subjective memory difficulties may be provoked by a variety of factors. To address these issues, we compared 100 patients with epilepsy and 57 healthy controls by means of our Questionnaire of Memory Efficiency, the State-Trait Anxiety Inventory, the Self-Rating Depression Scale and a battery of tests. The Chronbach test showed the Questionnaire of Memory Efficiency to be satisfactorily reliable. Patients reported significantly greater memory difficulties and higher levels of anxiety and depression than controls. Questionnaire of Memory Efficiency scores correlated with anxiety and depression levels, as well as with memory and learning test scores and regression analysis showed that anxiety, depression and visual learning had the most consistent explanatory power. No correlation was found with clinical variables or the presence of detectable brain lesion. Patients undergoing polytherapy or treatment for long periods reported the greatest memory difficulties. These findings suggest that subjective perception of memory failure reflects objective memory impairment. However, emotional factors and low self-esteem may bloat the reporting of everyday memory difficulties. The Questionnaire of Memory Efficiency seems able to provide information about everyday memory problems in patients with epilepsy that may be useful for planning neuropsychological counselling or rehabilitation.

Visual learning on a selective reminding procedure and delayed recall in patients with temporal lobe epilepsy

Summary: We administered a visual selective reminding procedure for the learning of designs to healthy controls and to left or right temporal lobe epilepsy (TLE) patients without demonstrable brain lesions. In comparison with the other groups, right TLE patients showed a deficit of learning characterized by an impairment in storing visual material and consistently retrieving it from long‐term memory. Patients with left TLE performed similarly to controls. These data are consistent with the hypothesis of right hippocampal involvement in the learning of nonverbal material. Delayed retrieval of learned material was similar in all the subject groups tested at long time intervals, suggesting the impairment of learning in patients with right TLE does not necessarily imply a subsequent deficit in the retrieval of stored information. This finding may agree with the opinion that distinct functional systems subserve learning and memory.

The contribution of neuropsychology to diagnostic assessment in epilepsy

Neuropsychology plays a vital role in the treatment of epilepsy, providing information on the effects of seizures on higher cortical functions through the measurement of behavioral abilities and disabilities. This is accomplished through the design, administration and interpretation of neuropsychological tests, including those used in functional neuroimaging or cortical mapping and in intracarotid anesthetic procedures. The objective of this paper is to define and summarize in some detail the role and methods of neuropsychologists in specialized epilepsy centers. Included are information and recommendations regarding basic ingredients of a thorough neuropsychological assessment in the epilepsy setting, as well as suggestions for an abbreviated alternative exam when needed, with emphasis on functions associated with specific brain regions. The paper is intended for novice and experienced neuropsychologists to enable them to develop or evaluate their current practices, and also for other clinicians, who seek a better understanding of the methodology underlying the neuropsychological input to their work.

Semantic memory in partial epilepsy: verbal and non-verbal deficits and neuroanatomical relationships

Semantic memory was evaluated in 124 epilepsy patients, including 84 with left (n=44) or right temporal lobe epilepsy (TLE) (n=40) and 40 with left (n=25) or right frontal lobe epilepsy (FLE) (n=15), in order to determine their verbal and visual deficits, and the neuroanatomical relationships between them. The controls were 35 healthy subjects. Semantic memory was assessed by means of Picture Naming, Picture Pointing, the verbal Pyramid and Palm Trees Test (PPTT), the visual PPTT, Object Decision Hard, and Drawing From Memory. Episodic memory was assessed by means of the Short Story, Reys Complex Figure, the Verbal and Visual Selective Reminding Procedure and Brown-Peterson Procedure. Factor analysis of the epilepsy patients distinguished their semantic memory scores from other neuropsychological domains. The semantic memory factor was significantly related to the side of the epileptic region, with lower scores in the left hemisphere and left TLE patients. In comparison with the controls, the left TLE patients were significantly impaired on Picture Naming, Picture Pointing, and Object Decision Hard. Subsequent analyses showed that, in comparison with the controls and the right TLE patients, the left TLE patients with lateral temporal lobe lesions were impaired in Picture Naming whereas, in comparison with the controls, the left TLE patients with mesial temporal lobe lesions were impaired in Object Decision Hard. On the contrary, the episodic memory factor was not related to the side of the epileptic region, and a few material-specific tests revealed opposite impairments in the left and right hemisphere patients. These results show that left TLE may cause semantic memory deficits involving verbal and visual information. Unlike the material-specific pattern of episodic memory, this pattern of impairment is in line with the view of an amodal semantic store in which all of the information about a thing overlaps. The semantic memory impairment may reflect damage in the lateral and mesial temporal lobe regions that impair neocortical functions in storing and retrieving information or hippocampal functions in processing meaningful stimuli.

Positive response to immunomodulatory therapy in an adult patient with Rasmussen’s encephalitis

Rasmussen’s encephalitis (RE) is a rare and progressive neurologic condition of uncertain etiology that typically has a childhood onset. The authors describe a 45-year-old woman with adult-onset progressive aphasia, right hemiparesis, severe drug refractory epilepsy, and left cerebral hemisphere atrophy. High-dose corticosteroids and plasmapheresis were not effective. She improved with high-dose therapy with human IV immunoglobulin.

The contribution of spirituality to quality of life in focal epilepsy

People with epilepsy of comparable severity may differ widely in quality of life (QOL), suggesting a role for unexplored individual aspects. This study considered the possible role of spirituality. Thirty-two patients with focal epilepsy completed scales for QOL (World Heath Organization QOL, WHOQOL 100), spirituality (WHO Spirituality, Religiousness, and Personal Beliefs), depression, anxiety, and cognitive efficiency, as well as neuropsychological testing. The QOL and spirituality scales exhibited satisfactory internal consistency. Factor analyses of the scale and test scores yielded separate spiritual (Personal Meaning, Inner Energy, Awe and Transcendence, and Openness), affective (Mood), and cognitive (Cognition, Memory, and Perceived Cognitive Efficiency) factors. The total WHOQOL 100 score was significantly predicted by the Awe and Transcendence and Mood factors. The spiritual, Mood, and Cognition factors significantly predicted single QOL domains. These preliminary results highlight the contribution of spirituality to QOL in epilepsy, encouraging future studies. This could influence the conceptualization and assessment of QOL in these patients.

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.

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

Although the pathological hallmarks of Alzheimers 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.