Anna Rita Giovagnoli

Publications of Anna Rita Giovagnoli

• Effectiveness of valproate for the treatment of manic-like behavior in X-linked adrenoleukodystrophy.

  Authors: Ettore Salsano, Orsola Gambini, Anna Rita Giovagnoli, Laura Farina, Graziella Uziel, Davide Pareyson

  Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 11/2011;

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

  Authors: Anna Rita Giovagnoli, Silvana Franceschetti, Fabiola Reati, Annalisa Parente, Carmelo Maccagnano, Flavio Villani, Roberto Spreafico

  Epilepsia. 08/2011; 52(11):1995-2002.

  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 cognitiveTheory 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. 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. 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). 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.

• Variability of the clinical phenotype in an Italian family with dementia associated with an intronic deletion in the GRN gene.

  Authors: Gabriella Marcon, Giacomina Rossi, Giorgio Giaccone, Anna Rita Giovagnoli, Elena Piccoli, Sergio Zanini, Onelio Geatti, Vito Toso, Marina Grisoli, Fabrizio Tagliavini

  Journal of Alzheimer's disease : JAD. 06/2011; 26(3):583-90.

  Mutations in the progranulin gene (GRN) were recently identified as an important cause of familial frontotemporal dementia (FTD). More than 60 pathogenic mutations have been reported up to now andMutations in the progranulin gene (GRN) were recently identified as an important cause of familial frontotemporal dementia (FTD). More than 60 pathogenic mutations have been reported up to now and prominent phenotypic variability within and among affected kindreds has been described. We have studied an Italian family with clinical evidence of dementia, and here we report detailed clinical records, imaging, sequential neurological examinations, cognitive assessments, and genetic analysis of three affected members of the same generation. Genetic analysis revealed the presence of the null mutation IVS6 + 5_8delGTGA in GRN, leading to haploinsufficiency, as documented by mRNA analysis. The mutation is associated with wide variation of the clinical phenotype, ranging from FTD to Alzheimer's disease and to a rapidly-progressive dementia. In summary, the patients of this kindred showed highly variable clinical features that do not have a close correspondence with the pattern of the cerebral atrophy. Our data extend the phenotypic spectrum and the complexity of neurodegenerative diseases linked to GRN mutations.

• Accuracy of pre-surgical fMRI confirmed by subsequent crossed aphasia.

  Authors: Paolo Vitali, Nina Dronkers, Alexander Pincherle, Anna Rita Giovagnoli, Carlo Marras, Ludovico D'Incerti, Francesco Ghielmetti, Roberto Spreafico, Flavio Villani

  Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 11/2010; 32(1):175-80.

  Atypical patterns of language activation in functional MRI (fMRI) are not unusual, particularly in patients with severe epilepsy. Still, the functional significance of these activations is underAtypical patterns of language activation in functional MRI (fMRI) are not unusual, particularly in patients with severe epilepsy. Still, the functional significance of these activations is under debate. We describe a case of a right-handed patient affected by drug-refractory right temporal lobe epilepsy in whom pre-surgical fMRI showed bilateral language activations, greater in the right hemisphere (RH). After surgery, a right subdural hematoma caused epileptic status and severe aphasia. This post-surgical complication of a crossed aphasia confirmed the prior fMRI findings of RH language thus stressing the value of pre-surgical fMRI evaluations, even when surgery is planned in the RH of a right-handed patient.

• Mitochondrial dementia: a sporadic case of progressive cognitive and behavioral decline with hearing loss due to the rare m.3291T>C MELAS mutation.

  Authors: Ettore Salsano, Anna Rita Giovagnoli, Lucia Morandi, Carmelo Maccagnano, Eleonora Lamantea, Chiara Marchesi, Massimo Zeviani, Davide Pareyson

  Journal of the neurological sciences. 10/2010; 300(1-2):165-8.

  We report the case of a 23-year-old Italian female harboring the rare m.3291T>C mutation in the MT-TL1 gene, that encodes the mitochondrial transfer RNA for leucine 1 (UUA/G). MT-TL1 mutationsWe report the case of a 23-year-old Italian female harboring the rare m.3291T>C mutation in the MT-TL1 gene, that encodes the mitochondrial transfer RNA for leucine 1 (UUA/G). MT-TL1 mutations usually cause the MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) syndrome. Our patient, however, suffered from a non-syndromic mitochondrial disorder (MID), clinically characterized by progressive cognitive and behavioral decline, and hearing loss; brain MRI disclosed diffuse supratentorial and infratentorial atrophy; EKG revealed a Wolff-Parkinson-White syndrome; combined neuroleptic and antidepressant treatment markedly improved her behavioral symptoms. This case expands the clinical spectrum of non-syndromic MIDs, and further confirms that no obvious genotype-phenotype correlation exists for the m.3291T>C DNA mutation; indeed, this mutation has been previously reported in a Japanese child, who suffered from MELAS, and in an Italian child, who presented an apparently isolated mild myopathy. Moreover, it supports the hypothesis that at least in MT-TL1-related MIDs, dementia may be caused by a progressive neurodegenerative process, rather than by injury accumulation due to stroke-like episodes. Finally, our case suggests that common neuroleptic and antidepressant drugs may be clinically efficacious in the management of psychiatric symptoms associated with MIDs.

• The Role of Neuropsychology in Distinguishing the Posterior Cortical Atrophy Syndrome and Alzheimer'S Disease.

  Authors: Anna Aresi, Anna Rita Giovagnoli

  Journal of Alzheimer's disease : JAD. 07/2009;

  This study investigated the neuropsychological hallmarks of posterior cortical atrophy (PCA). Seventeen patients with PCA, 17 patients with probable Alzheimer's disease (PAD), and 17 healthyThis study investigated the neuropsychological hallmarks of posterior cortical atrophy (PCA). Seventeen patients with PCA, 17 patients with probable Alzheimer's disease (PAD), and 17 healthy age-matched subjects underwent neuropsychological testing for abstract reasoning, visuospatial abilities, memory, language, executive functions, praxes, and attention. The PCA patients were significantly more impaired in visual perception, spatial memory, visual attention, and visuospatial reasoning compared to the PAD patients who were relatively more impaired in episodic memory. In the PCA group, no test score correlated with disease duration or age of clinical onset, whereas, in the PAD group, several scores correlated with disease duration. Compared to the healthy subjects, both patient groups showed multiple cognitive deficits. Thus, PCA is characterised by distinctive visuospatial deficits that reflect the distribution of brain damage and contrast with the memory impairment of PAD patients. Specific neuropsychological tests may contribute to early identification of cortical dementia for diagnostic and research purposes.

• A recessive mutation in the APP gene with dominant-negative effect on amyloidogenesis.

  Authors: Giuseppe Di Fede, Marcella Catania, Michela Morbin, Giacomina Rossi, Silvia Suardi, Giulia Mazzoleni, Marco Merlin, Anna Rita Giovagnoli, Sara Prioni, Alessandra Erbetta [......] Antonio Bastone, Marten Beeg, Claudia Manzoni, Bruna Francescucci, Alberto Spagnoli, Laura Cantù, Elena Del Favero, Efrat Levy, Mario Salmona, Fabrizio Tagliavini

  Science (New York, N.Y.). 04/2009; 323(5920):1473-7.

  beta-Amyloid precursor protein (APP) mutations cause familial Alzheimer's disease with nearly complete penetrance. We found an APP mutation [alanine-673-->valine-673 (A673V)] that causes disease onlybeta-Amyloid precursor protein (APP) mutations cause familial Alzheimer's 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 beta-amyloid (Abeta) production and formation of amyloid fibrils in vitro. Co-incubation of mutated and wild-type peptides conferred instability on Abeta 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 Alzheimer's disease.

• A novel italian presenilin 2 gene mutation with prevalent behavioral phenotype.

  Authors: Gabriella Marcon, Giuseppe Di Fede, Giorgio Giaccone, Giacomina Rossi, Anna Rita Giovagnoli, Elio Maccagnano, Fabrizio Tagliavini

  Journal of Alzheimer's disease : JAD. 04/2009; 16(3):509-11.

  Presenilin mutations are the main cause of familial Alzheimer's disease. So far, more than 160 mutations in the Presenilin 1 gene (PSEN1) and approximately 10 mutations in the homologous Presenilin 2Presenilin mutations are the main cause of familial Alzheimer's disease. So far, more than 160 mutations in the Presenilin 1 gene (PSEN1) and approximately 10 mutations in the homologous Presenilin 2 gene (PSEN2) have been identified. Some PSEN1 mutations are associated with a phenotype fulfilling the clinical criteria of frontotemporal dementia. In PSEN2, T122P and M239V mutations presented with severe behavioral disturbances. We describe an Italian patient with a novel PSEN2 mutation (Y231C) who showed behavioral abnormalities and language impairment as presenting symptoms, with later involvement of other cognitive abilities, particularly of posterior functions.

• Neuropsychological predictors of quality of life in focal epilepsy.

  Authors: Rute F Meneses, J L Pais-Ribeiro, António Martins da Silva, Anna Rita Giovagnoli

  Seizure : the journal of the British Epilepsy Association. 02/2009;

  Spontaneous complaints of outpatients with focal epilepsy often stress the relationship between cognitive deficits and Quality of Life (QOL). Consequently, the aim of the present study was to findSpontaneous complaints of outpatients with focal epilepsy often stress the relationship between cognitive deficits and Quality of Life (QOL). Consequently, the aim of the present study was to find the best neuropsychological predictors of QOL in individuals with focal epilepsy, in order to guide their ambulatory health care. A sample of 71 Portuguese patients was studied: 40 female, 47 married, with a mean age of 37.48 years (S.D.=11.79, 16-62), mean education of 7.93 (S.D.=4.05, 3-17), and focal epilepsy of moderate severity. A Socio-demographic and Clinical Questionnaire, the SF-36 v1, the Cognitive Functioning Scale from the ESI-55, a Seizure Control scale (items from the Liverpool Seizure Severity Scale), and several neuropsychological tests were used. Semantic Fluency was the only predictor of Physical Functioning, Role Functioning - Physical, and Mental Health; I.A. Test predicted Bodily Pain; and Attentive Matrices predicted General Health, Vitality, and Role Functioning - Emotional. The Mental Component of the SF-36 v1 was predicted by Attentive Matrices, and the Physical Component was predicted by Semantic Fluency. Cognitive Functioning was predicted by the Token Test. Social Functioning and Seizure Control presented no statistically significant correlation with the neuropsychological indicators used. These results underscore the importance of cognitive performance to the QOL of individuals with focal epilepsy, supporting the systematic screening of cognitive performance in this population. Additionally, they suggest cognitive rehabilitation has the potential to improve these individuals' QOL.

• Cognitive deficits in familial Alzheimer's disease associated with M239V mutation of presenilin 2.

  Authors: Anna Rita Giovagnoli, Gabriella Marcon, Giorgio Giaccone, Anna Maria Confaloni, Fabrizio Tagliavini

  Dementia and geriatric cognitive disorders. 02/2006; 22(3):238-43.

  The neuropsychological assessment of non-demented subjects with gene mutation of familial Alzheimer's disease (AD) provides a model for exploring the early cognitive features of the disease. WeThe neuropsychological assessment of non-demented subjects with gene mutation of familial Alzheimer's disease (AD) provides a model for exploring the early cognitive features of the disease. We evaluated 1 patient and 6 non-demented subjects belonging to a family with AD with M239V mutation of the presenilin 2 gene, aiming to verify the contribution of specific cognitive patterns to the characterization of familial AD. One patient, 3 non-demented subjects with M239V mutation and 3 subjects without mutation from the same family underwent neuropsychological testing. The patient's cognitive profile was characterized by anosognosia, visuospatial agnosia, apraxia and fluent aphasia. Of the 3 non-demented subjects with mutation, 1 showed no deficits, another constructive apraxia and the third spatial perception and memory deficits. The 3 subjects without mutation showed normal abilities. The cognitive deficits of the non-demented subjects with mutations indicate focal dysfunction of the posterior cortical areas, resembling the more extended parieto-occipito-temporal dysfunction of the demented patient. Such grading of visuospatial, praxis, and language impairments highlights a distinctive pattern related to the M239V mutation of the presenilin 2 gene.

• Characteristics of verbal semantic impairment in left hemisphere epilepsy.

  Authors: Anna Rita Giovagnoli

  Neuropsychology. 08/2005; 19(4):501-8.

  Fifty-two patients with partial epilepsy of left (n=30) or right (n=22) hemisphere origin were compared with 23 healthy subjects to explore the characteristics and mechanisms of verbal semanticFifty-two patients with partial epilepsy of left (n=30) or right (n=22) hemisphere origin were compared with 23 healthy subjects to explore the characteristics and mechanisms of verbal semantic deficits. Picture Naming, Picture Pointing, and the Semantic Questionnaire assessed semantic retrieval, comprehension, and judgment, respectively. In comparison with the controls and right hemisphere patients, the left hemisphere patients showed impairments on Picture Naming and the Semantic Questionnaire. On Picture Naming, the left hemisphere patients made significant omissions and intracategorical errors; on the Semantic Questionnaire, they made errors at superordinate and subordinate levels of information, they made more errors in relation to living than nonliving things, and there were significant associations between their Picture Naming and Semantic Questionnaire scores. In this population, the mixed profiles of semantic deficits suggests the coexistence of altered retrieval and information loss.

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

  Authors: Anna Rita Giovagnoli, Alessandra Erbetta, Flavio Villani, Giuliano Avanzini

  Neuropsychologia. 02/2005; 43(10):1482-92.

  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),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, Rey's 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.