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1. How to detect affect recognition alterations in amyotrophic lateral sclerosis

Author

Castelnovo, Veronica, Canu, Elisa, Aiello, Edoardo Nicolò, Curti, Beatrice, Sibilla, Elisa, Torre, Silvia, Freri, Fabiola, Tripodi, Chiara, Lumaca, Laura, Spinelli, Edoardo Gioele, Schito, Paride, Russo, Tommaso, Falzone, Yuri, Verde, Federico, Silani, Vincenzo, Ticozzi, Nicola, Sturm, Virginia E., Rankin, Katherine P., Gorno-Tempini, Maria Luisa, Poletti, Barbara, Filippi, Massimo, and Agosta, Federica

Published
2024
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2. Clinical and neuroanatomical characterization of the semantic behavioral variant of frontotemporal dementia in a multicenter Italian cohort

Author

Ghirelli, Alma, Spinelli, Edoardo Gioele, Canu, Elisa, Basaia, Silvia, Castelnovo, Veronica, Cecchetti, Giordano, Sibilla, Elisa, Domi, Teuta, Magnani, Giuseppe, Caso, Francesca, Caroppo, Paola, Prioni, Sara, Villa, Cristina, Rossi, Giacomina, Tremolizzo, Lucio, Appollonio, Ildebrando, Verde, Federico, Ticozzi, Nicola, Silani, Vincenzo, Filippi, Massimo, and Agosta, Federica

Published
2024
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6. Case report: coexistence of C9orf72 expansion and progranulin mutation in a case of genetic frontotemporal dementia—clinical features and neuroimaging correlates

Author

Ghirelli, Alma, Spinelli, Edoardo Gioele, Canu, Elisa, Domi, Teuta, Basaia, Silvia, Castelnovo, Veronica, Pozzi, Laura, Magnani, Giuseppe, Caso, Francesca, Caroppo, Paola, Prioni, Sara, Villa, Cristina, Riva, Nilo, Quattrini, Angelo, Carrera, Paola, Filippi, Massimo, and Agosta, Federica

Published
2023
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8. Resting state functional brain networks associated with emotion processing in frontotemporal lobar degeneration

Author

Canu, Elisa, Calderaro, Davide, Castelnovo, Veronica, Basaia, Silvia, Magno, Maria Antonietta, Riva, Nilo, Magnani, Giuseppe, Caso, Francesca, Caroppo, Paola, Prioni, Sara, Villa, Cristina, Pain, Debora, Mora, Gabriele, Tremolizzo, Lucio, Appollonio, Ildebrando, Poletti, Barbara, Silani, Vincenzo, Filippi, Massimo, and Agosta, Federica

Published
2022
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9. Cognitive, EEG, and MRI features of COVID-19 survivors: a 10-month study

Author

Cecchetti, Giordano, Agosta, Federica, Canu, Elisa, Basaia, Silvia, Barbieri, Alessandra, Cardamone, Rosalinda, Bernasconi, Maria Paola, Castelnovo, Veronica, Cividini, Camilla, Cursi, Marco, Vabanesi, Marco, Impellizzeri, Matteo, Lazzarin, Serena Marita, Fanelli, Giovanna Franca, Minicucci, Fabio, Giacalone, Giacomo, Falini, Andrea, Falautano, Monica, Rovere-Querini, Patrizia, Roveri, Luisa, and Filippi, Massimo

Published
2022
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11. Clinical and Neuroanatomical Characterization of the Semantic Behavioural Variant of Frontotemporal Dementia in a Multicentre Italian Cohort (P4-9.004)

Author

Ghirelli, Alma, primary, Spinelli, Edoardo, additional, Canu, Elisa, additional, Basaia, Silvia, additional, Castelnovo, Veronica, additional, Cecchetti, Giordano, additional, Sibilla, Elisa, additional, Magnani, Giuseppe, additional, Caso, Francesca, additional, Caroppo, Paola, additional, Prioni, Sara, additional, Villa, Cristina, additional, Tremolizzo, Lucio, additional, Appollonio, Ildebrando, additional, Verde, Federico, additional, Ticozzi, Nicola, additional, Silani, Vincenzo, additional, Filippi, Massimo, additional, and Agosta, Federica, additional

Published
2024
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15. Clinical and neuroanatomical characterization of the semantic behavioral variant of frontotemporal dementia in a multicenter Italian cohort

Author

Ghirelli, A, Spinelli, E, Canu, E, Basaia, S, Castelnovo, V, Cecchetti, G, Sibilla, E, Domi, T, Magnani, G, Caso, F, Caroppo, P, Prioni, S, Villa, C, Rossi, G, Tremolizzo, L, Appollonio, I, Verde, F, Ticozzi, N, Silani, V, Filippi, M, Agosta, F, Ghirelli, Alma, Spinelli, Edoardo Gioele, Canu, Elisa, Basaia, Silvia, Castelnovo, Veronica, Cecchetti, Giordano, Sibilla, Elisa, Domi, Teuta, Magnani, Giuseppe, Caso, Francesca, Caroppo, Paola, Prioni, Sara, Villa, Cristina, Rossi, Giacomina, Tremolizzo, Lucio, Appollonio, Ildebrando, Verde, Federico, Ticozzi, Nicola, Silani, Vincenzo, Filippi, Massimo, Agosta, Federica, Ghirelli, A, Spinelli, E, Canu, E, Basaia, S, Castelnovo, V, Cecchetti, G, Sibilla, E, Domi, T, Magnani, G, Caso, F, Caroppo, P, Prioni, S, Villa, C, Rossi, G, Tremolizzo, L, Appollonio, I, Verde, F, Ticozzi, N, Silani, V, Filippi, M, Agosta, F, Ghirelli, Alma, Spinelli, Edoardo Gioele, Canu, Elisa, Basaia, Silvia, Castelnovo, Veronica, Cecchetti, Giordano, Sibilla, Elisa, Domi, Teuta, Magnani, Giuseppe, Caso, Francesca, Caroppo, Paola, Prioni, Sara, Villa, Cristina, Rossi, Giacomina, Tremolizzo, Lucio, Appollonio, Ildebrando, Verde, Federico, Ticozzi, Nicola, Silani, Vincenzo, Filippi, Massimo, and Agosta, Federica

Abstract

Background: Semantic behavioral variant frontotemporal dementia (sbvFTD) is a neurodegenerative condition presenting with specific behavioral and semantic derangements and predominant atrophy of the right anterior temporal lobe (ATL). The objective was to evaluate clinical, neuropsychological, neuroimaging, and genetic features of an Italian sbvFTD cohort, defined according to recently proposed guidelines, compared to semantic variant primary progressive aphasia (svPPA) and behavioral variant FTD (bvFTD) patients. Methods: Fifteen sbvFTD, sixty-three bvFTD, and twenty-five svPPA patients and forty controls were enrolled. Patients underwent clinical, cognitive evaluations, and brain MRI. Symptoms of bvFTD patients between onset and first visit were retrospectively recorded and classified as early and late. Grey matter atrophy was investigated using voxel-based morphometry. Results: sbvFTD experienced early criteria-specific symptoms: world, object and person-specific semantic loss (67%), complex compulsions and rigid thought (60%). Sequentially, more behavioral symptoms emerged (apathy/inertia, loss of empathy) along with non-criteria-specific symptoms (anxiety, suspiciousness). sbvFTD showed sparing of attentive/executive functions, especially compared to bvFTD and better language functions compared to svPPA. All sbvFTD patients failed at the famous face recognition test and more than 80% failed in understanding written metaphors and humor. At MRI, sbvFTD had predominant right ATL atrophy, almost specular to svPPA. Three sbvFTD patients presented pathogenic genetic variants. Conclusion: We replicated the application of sbvFTD diagnostic guidelines in an independent Italian cohort, demonstrating that the presence of person-specific semantic knowledge loss and mental rigidity, along with preserved executive functions and a predominant right ATL atrophy with sparing of frontal lobes, should prompt a diagnosis of sbvFTD.

Published
2024

16. Clinical and neuroimaging characterization of the first frontotemporal dementia family carrying the MAPT p.K298E mutation

Author

Pozzi, F, Aprea, V, Giovannelli, G, Lattuada, F, Crivellaro, C, Bertola, F, Castelnovo, V, Canu, E, Filippi, M, Appollonio, I, Ferrarese, C, Agosta, F, Tremolizzo, L, Pozzi, Federico Emanuele, Aprea, Vittoria, Giovannelli, Ginevra, Lattuada, Francesca, Crivellaro, Cinzia, Bertola, Francesca, Castelnovo, Veronica, Canu, Elisa, Filippi, Massimo, Appollonio, Ildebrando, Ferrarese, Carlo, Agosta, Federica, Tremolizzo, Lucio, Pozzi, F, Aprea, V, Giovannelli, G, Lattuada, F, Crivellaro, C, Bertola, F, Castelnovo, V, Canu, E, Filippi, M, Appollonio, I, Ferrarese, C, Agosta, F, Tremolizzo, L, Pozzi, Federico Emanuele, Aprea, Vittoria, Giovannelli, Ginevra, Lattuada, Francesca, Crivellaro, Cinzia, Bertola, Francesca, Castelnovo, Veronica, Canu, Elisa, Filippi, Massimo, Appollonio, Ildebrando, Ferrarese, Carlo, Agosta, Federica, and Tremolizzo, Lucio

Abstract

We present an in-depth clinical and neuroimaging analysis of a family carrying the MAPT K298E mutation associated with frontotemporal dementia (FTD). Initial identification of this mutation in a single clinical case led to a comprehensive investigation involving four affected siblings allowing to elucidate the mutation's phenotypic expression. A 60-year-old male presented with significant behavioral changes and progressed rapidly, exhibiting speech difficulties and cognitive decline. Neuroimaging via FDG-PET revealed asymmetrical frontotemporal hypometabolism. Three siblings subsequently showed varied but consistent clinical manifestations, including abnormal behavior, speech impairments, memory deficits, and motor symptoms correlating with asymmetric frontotemporal atrophy observed in MRI scans. Based on the genotype–phenotype correlation, we propose that the p.K298E mutation results in early-onset behavioral variant FTD, accompanied by a various constellation of speech and motor impairment. This detailed characterization expands the understanding of the p.K298E mutation's clinical and neuroimaging features, underlining its role in the pathogenesis of FTD. Further research is crucial to comprehensively delineate the clinical and epidemiological implications of the MAPT p.K298E mutation.

Published
2024

17. Structural and Functional Brain Network Connectivity at Different King's Stages in Patients With Amyotrophic Lateral Sclerosis

Author

Spinelli, Edoardo G., primary, Ghirelli, Alma, additional, Basaia, Silvia, additional, Canu, Elisa, additional, Castelnovo, Veronica, additional, Cividini, Camilla, additional, Russo, Tommaso, additional, Schito, Paride, additional, Falzone, Yuri M., additional, Riva, Nilo, additional, Filippi, Massimo, additional, and Agosta, Federica, additional

Published
2024
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18. Modeling pathological spread through the structural connectome in the FTLD spectrum

Author

Agosta, Federica, primary, Basaia, Silvia, additional, Facente, Federica, additional, Cividini, Camilla, additional, Spinelli, Edoardo Gioele, additional, Canu, Elisa, additional, Castelnovo, Veronica, additional, Ghirelli, Alma, additional, Magnani, Giuseppe, additional, Caso, Francesca, additional, Riva, Nilo, additional, Caroppo, Paola, additional, Prioni, Sara, additional, Villa, Cristina, additional, Tremolizzo, Lucio, additional, Appollonio, Ildebrando, additional, Verde, Federico, additional, Silani, Vincenzo, additional, and Filippi, Massimo, additional

Published
2023
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23. Characterization of FTLD spectrum through advanced diffusion-weighted MRI metrics: a connectome approach (P11-6.003)

Author

Agosta, Federica, primary, Basaia, Silvia, additional, Facente, Federica, additional, Cividini, Camilla, additional, Spinelli, Edoardo, additional, Canu, Elisa, additional, Castelnovo, Veronica, additional, Magnani, Giuseppe, additional, Caso, Francesca, additional, Caroppo, Paola, additional, Prioni, Sara, additional, Villa, Cristina, additional, Tremolizzo, Lucio, additional, Appollonio, Ildebrando, additional, Silani, Vincenzo, additional, and Filippi, Massimo, additional

Published
2023
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24. Stepwise functional brain architecture from disease epicenter correlates with atrophy in progressive supranuclear palsy (P11-6.001)

Author

Spinelli, Edoardo, primary, Ghirelli, Alma, additional, Bottale, Ilaria, additional, Basaia, Silvia, additional, Cividini, Camilla, additional, Volonte, M. Antonietta, additional, Galantucci, Sebastiano, additional, Magnani, Giuseppe, additional, Caso, Francesca, additional, Canu, Elisa, additional, Castelnovo, Veronica, additional, Caroppo, Paola, additional, Prioni, Sara, additional, Villa, Cristina, additional, Josephs, Keith, additional, Whitwell, Jennifer, additional, Agosta, Federica, additional, and Filippi, Massimo, additional

Published
2023
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26. Functional Connectivity From Disease Epicenters in Frontotemporal Dementia

Author

Agosta, Federica, primary, Spinelli, Edoardo Gioele, additional, Basaia, Silvia, additional, Cividini, Camilla, additional, Falbo, Francesco, additional, Pavone, Costanza, additional, Riva, Nilo, additional, Canu, Elisa, additional, Castelnovo, Veronica, additional, Magnani, Giuseppe, additional, Caso, Francesca, additional, Caroppo, Paola, additional, Prioni, Sara, additional, Villa, Cristina, additional, Tremolizzo, Lucio, additional, Appollonio, Ildebrando, additional, Silani, Vincenzo, additional, Josephs, Keith Anthony, additional, Whitwell, Jennifer, additional, and Filippi, Massimo, additional

Published
2023
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28. Functional Connectivity From Disease Epicenters in Frontotemporal Dementia

Author

Agosta, F, Spinelli, E, Basaia, S, Cividini, C, Falbo, F, Pavone, C, Riva, N, Canu, E, Castelnovo, V, Magnani, G, Caso, F, Caroppo, P, Prioni, S, Villa, C, Tremolizzo, L, Appollonio, I, Silani, V, Josephs, K, Whitwell, J, Filippi, M, Agosta, Federica, Spinelli, Edoardo Gioele, Basaia, Silvia, Cividini, Camilla, Falbo, Francesco, Pavone, Costanza, Riva, Nilo, Canu, Elisa, Castelnovo, Veronica, Magnani, Giuseppe, Caso, Francesca, Caroppo, Paola, Prioni, Sara, Villa, Cristina, Tremolizzo, Lucio, Appollonio, Ildebrando, Silani, Vincenzo, Josephs, Keith Anthony, Whitwell, Jennifer, Filippi, Massimo, Agosta, F, Spinelli, E, Basaia, S, Cividini, C, Falbo, F, Pavone, C, Riva, N, Canu, E, Castelnovo, V, Magnani, G, Caso, F, Caroppo, P, Prioni, S, Villa, C, Tremolizzo, L, Appollonio, I, Silani, V, Josephs, K, Whitwell, J, Filippi, M, Agosta, Federica, Spinelli, Edoardo Gioele, Basaia, Silvia, Cividini, Camilla, Falbo, Francesco, Pavone, Costanza, Riva, Nilo, Canu, Elisa, Castelnovo, Veronica, Magnani, Giuseppe, Caso, Francesca, Caroppo, Paola, Prioni, Sara, Villa, Cristina, Tremolizzo, Lucio, Appollonio, Ildebrando, Silani, Vincenzo, Josephs, Keith Anthony, Whitwell, Jennifer, and Filippi, Massimo

Abstract

Background and ObjectivesMRI connectomics is an ideal tool to test a network-based model of pathologic propagation from a disease epicenter in neurodegenerative disorders. In this study, we used a novel graph theory-based MRI paradigm to explore functional connectivity reorganization, discerning between direct and indirect connections from disease epicenters, and its relationship with neurodegeneration across clinical presentations of the frontotemporal dementia (FTD) spectrum, including behavioral variant of FTD (bvFTD), nonfluent variant of primary progressive aphasia (nfvPPA), and semantic variant of primary progressive aphasia (svPPA).MethodsIn this observational cross-sectional study, disease epicenters were defined as the peaks of atrophy of a cohort of patients with high confidence of frontotemporal lobar degeneration pathology (Mayo Clinic). These were used as seed regions for stepwise functional connectivity (SFC) analyses in an independent (Milan) set of patients with FTD to assess connectivity in regions directly and indirectly connected to the epicenters. Correlations between SFC architecture in healthy conditions and atrophy patterns in patients with FTD were also tested.ResultsAs defined by comparing the 42 Mayo Clinic patients with 15 controls, disease epicenters were the left anterior insula for bvFTD, left supplementary motor area for nfvPPA, and left inferior temporal gyrus (ITG) for svPPA. Compared with 94 age-matched controls, patients with bvFTD (n = 64) and nfvPPA (n = 34) of the Milan cohort showed widespread decreased SFC in bilateral cortical regions with direct/indirect connections with epicenters and increased SFC either in directly connected regions, physically close to the respective seed region, or in more distant cortical/cerebellar areas with indirect connections. Across all link steps, svPPA (n = 36) showed SFC decrease mostly within the temporal lobes, with co-occurrent SFC increase in cerebellar regions at indirect link steps. The

Published
2023

29. Italian reference values and brain correlates of verbal fluency index – vs standard verbal fluency test – to assess executive dysfunction in ALS.

Author

Canu, Elisa, Castelnovo, Veronica, Rancoita, Paola MV, Leocadi, Michela, Lamanuzzi, Alessandra, Spinelli, Edoardo Gioele, Basaia, Silvia, Riva, Nilo, Poletti, Barbara, Solca, Federica, Verde, Federico, Ticozzi, Nicola, Silani, Vincenzo, Abrahams, Sharon, Filippi, Massimo, and Agosta, Federica

Subjects
*VERBAL behavior testing, *REFERENCE values, *ITALIAN language, *AMYOTROPHIC lateral sclerosis, *MOTOR cortex
Abstract

Objectives: In amyotrophic lateral sclerosis (ALS), verbal fluency index (Vfi) is used to investigate fluency accounting for motor impairment. This study has three aims: (1) to provide Vfi reference values from a cohort of Italian healthy subjects; (2) to assess the ability of Vfi reference values (vs standard verbal fluency test [VFT]) in distinguishing ALS patients with and without executive dysfunction; and (3) to investigate the association between Vfi and brain structural features of ALS patients. Methods: We included 180 healthy subjects and 157 ALS patients who underwent neuropsychological assessment, including VFT and Vfi, and brain MRI. Healthy subjects were split into four subgroups according to sex and education. For each subgroup, we defined the 95th percentile of Vfi as the cutoff. In ALS, the distributions of "abnormal" cases based on Vfi and standard VFT cutoffs were compared using Fisher's exact test. Using quantile regressions in patients, we assessed the association between Vfi and VFT scores, separately, with gray matter volumes and white matter (WM) tract integrity. Results: Applying Vfi and VFT cutoffs, 9 and 13% of ALS cases, respectively, had abnormal scores (p < 0.001). In ALS, while higher Vfi scores were associated with WM changes of callosal fibers linking supplementary motor area, lower VFT performances related to corticospinal tract alterations. Discussion: We provided Italian reference values for the spoken Vfi. Compared to VFT, Vfis are critical to disentangle motor and cognitive deficits in ALS. In patients, abnormal Vfis were associated with damage to WM tracts specifically involved in ideational information processing. [ABSTRACT FROM AUTHOR]

Published
2023
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31. BRAIN FUNCTIONAL CONNECTIVITY AND COGNITIVE DYSFUNCTION IN PATIENTS WITH MOTOR NEURON DISORDERS

Author

CASTELNOVO, VERONICA and Castelnovo, Veronica

Abstract

Motor neuron diseases (MND) are heterogeneous neurodegenerative disorders in which the possible presence of cognitive and/or behavioural symptoms is a universally known neuropsychological feature. Detecting even subtle cognitive changes in MND, monitoring them over time and identifying new markers both in terms of cognition and of neuroimaging is critical due to their considerable clinical impact. This thesis examines the presence of early markers of cognitive and behavioural alterations, of disease progression and brain correlates in MND patients, using specific neuropsychological evaluations and advanced magnetic resonance imaging (MRI) techniques. The results from this thesis demonstrated that computer-based neuropsychological batteries, rather than the standard ones’, are able to identify subtle cognitive changes in amyotrophic lateral sclerosis (ALS), unique to this condition. These findings highlight the need of specific, accurate and well- tolerated tools for monitoring cognitive deficits in MND. Assessing the resting-state functional connectivity (RS-FC) in ALS patients over 6 months, we observed an increased functional connectivity over time within the frontostriatal and the frontoparietal networks. RS-FC was related to patients’ frontal-executive dysfunction, and we identified the middle frontal gyrus as a potential core region in the framework of a frontoparietal functional disconnection, which is typical of frontotemporal lobar degeneration (FTLD). Finally, in a sample of cognitively/behaviourally unimpaired patients with ALS, we investigated the emotional processing and we observed that a lower performance in recognizing disgust was related with a reduced volume of the left pallidum and with a lower performance on the Edinburgh Cognitive and Behavioral ALS Screen, suggesting that altered disgust recognition could be an early marker of cognitive decline in ALS patients. In pure motor patients we also demonstrated an altered RS-FC between pallidum and the rest of the brain and, specifically, that a reduced left pallidum-temporo-striatal RS-FC may have a role in the lower ability of ALS patients in recognizing disgust. Taken together, our studies provide novel cognitive and imaging markers for detecting early signs of disease progression and for monitoring MND over time. Future studies are needed to verify whether the information of cognitive and MRI alterations may be able to classify new ALS patients with a FTLD-like progression at the single subject level. Le malattie del motoneurone (MND) sono malattie neurodegenerative eterogenee nelle quali la possibile presenza di disturbi cognitivi e/o comportamentali è una caratteristica neuropsicologica universalmente nota. Rilevare cambiamenti cognitivi, anche lievi, in pazienti con MND, monitorarli nel tempo ed identificare nuovi marcatori sia cognitivi che di neuroimaging è fondamentale dato il loro notevole impatto clinico. Questa tesi esplora la presenza di marcatori precoci di alterazioni cognitive e comportamentali, di progressione della malattia e di correlati neurali in pazienti con MND, utilizzando valutazioni neuropsicologiche specifiche e tecniche avanzate di risonanza magnetica (RM). I risultati di questa tesi hanno dimostrato che le batterie neuropsicologiche computerizzate, rispetto a quelle standard, sono in grado di identificare lievi cambiamenti cognitivi nella sclerosi laterale amiotrofica (SLA), unici di questa condizione. Questi risultati evidenziano la necessità di strumenti specifici, accurati e ben tollerati per monitorare i deficit cognitivi nelle MND. Studiando la connettività funzionale a riposo (RS-FC) nei pazienti con SLA nell'arco di 6 mesi, abbiamo osservato un aumento della connettività funzionale nel tempo all'interno delle reti frontostriatale e frontoparietale. La RS-FC era correlata alle alterazioni esecutive frontali dei pazienti, e abbiamo identificato il giro frontale medio come potenziale regione chiave nel quadro di una disconnessione funzionale frontoparietale, che è tipica della degenerazione lobare frontotemporale (DLFT). Infine, in un campione di pazienti con SLA senza disturbi cognitivi e comportamentali, abbiamo studiato l'elaborazione emotiva e abbiamo osservato che una ridotta abilità nel riconoscere il disgusto era correlata con un ridotto volume del pallido di sinistra e con una ridotta performance all'Edinburgh Cognitive and Behavioral ALS Screen, suggerendo che un alterato riconoscimento del disgusto potrebbe essere un indicatore precoce del declino cognitivo nei pazienti con SLA. In pazienti con SLA senza disturbi cognitivi e comportamentali abbiamo anche dimostrato un’alterata RS-FC tra il pallido e il resto del cervello e, in particolare, che una ridotta RS-FC pallido-temporo-striatale sinistra può avere un ruolo nella ridotta capacità dei pazienti con SLA di riconoscere il disgusto. In conclusione, i nostri studi forniscono nuovi marcatori cognitivi e di neuroimaging per rilevare i primi segni di progressione della malattia e per monitorare le MND nel tempo. Sono necessari studi futuri per verificare se le informazioni relative alle alterazioni cognitive e di RM possono essere in grado di classificare nuovi pazienti con SLA con una progressione simile ai pazienti con DLFT a livello del singolo soggetto.

Published
2022

32. A novel GRN mutation in an Italian patient with non-fluent variant of primary progressive aphasia at onset: a longitudinal case report.

Author

Castelnovo, Veronica, Canu, Elisa, Domi, Teuta, Pozzi, Laura, Vignaroli, Francesca, Gioele Spinelli, Edoardo, Ghirelli, Alma, Tondo, Giacomo, Comi, Cristoforo, Riva, Nilo, Quattrini, Angelo, Carrera, Paola, Filippi, Massimo, and Agosta, Federica

Subjects
SPEECH apraxia, EXECUTIVE function, POSITRON emission tomography, NEUROPSYCHOLOGICAL tests, APHASIA, FRONTOTEMPORAL lobar degeneration, GENETIC mutation
Abstract

Objectives: We report the clinical presentation and evolution of a case with a novel Progranulin gene (GRN) mutation and non-fluent language disturbances at onset. Materials and methods: A 60 year-old, white patient was followed due to a history of language disturbances. Eighteen months after onset, the patient underwent FDG positron emission tomography (PET), and at month 24 was hospitalized to perform neuropsychological evaluation, brain 3 T MRI, lumbar puncture for cerebrospinal fluid (CSF) analysis, and genotyping. At month 31, the patient repeated the neuropsychological evaluation and brain MRI. Results: At onset the patient complained prominent language production difficulties, such as effortful speech and anomia. At month 18, FDG-PET showed left fronto-temporal and striatal hypometabolism. At month 24, the neuropsychological evaluation reported prevalent speech and comprehension deficits. Brain MRI reported left fronto-opercular and striatal atrophy, and left frontal periventricular white matter hyperintensities (WMHs). Increased CSF total tau level was observed. Genotyping revealed a new GRN c.1018delC (p.H340TfsX21) mutation. The patient received a diagnosis of non-fluent variant of primary progressive aphasia (nfvPPA). At month 31, language deficits worsened, together with attention and executive functions. The patient presented also with behavioral disturbances, and a progressive atrophy in the left frontal-opercular and temporo-mesial region. Discussion and conclusion: The new GRN p.H340TfsX21 mutation resulted in a case of nfvPPA characterized by fronto-temporal and striatal alterations, typical frontal asymmetric WMHs, and a fast progression toward a widespread cognitive and behavioral impairment, which reflects a frontotemporal lobar degeneration. Our findings extend the current knowledge of the phenotypic heterogeneity among GRN mutation carriers. [ABSTRACT FROM AUTHOR]

Published
2023
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34. Functional Connectivity Rearrangements Propagating from Disease Epicenters in Frontotemporal Lobar Degeneration Variants (P12-3.001)

Author

Spinelli, Edoardo, primary, Falbo, Francesco, additional, Basaia, Silvia, additional, Cividini, Camilla, additional, Riva, Nilo, additional, Canu, Elisa, additional, Castelnovo, Veronica, additional, Magnani, Giuseppe, additional, Caso, Francesca, additional, Caroppo, Paola, additional, Prioni, Sara, additional, Rossi, Giacomina, additional, Tremolizzo, Lucio, additional, Appollonio, Ildebrando, additional, Silani, Vincenzo, additional, Filippi, Massimo, additional, and Agosta, Federica, additional

Published
2022
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35. Cognitive, EEG and MRI features of COVID-19 survivors: a 10-month study (P1-1.Virtual)

Author

Cecchetti, Giordano, primary, Agosta, Federica, additional, Canu, Elisa, additional, Basaia, Silvia, additional, Barbieri, Alessandra, additional, Cardamone, Rosalinda, additional, Bernasconi, Maria Paola, additional, Castelnovo, Veronica, additional, Cividini, Camilla, additional, Cursi, Marco, additional, Vabanesi, Marco, additional, Impellizzeri, Matteo, additional, Lazzarin, Serena Marita, additional, Fanelli, Giovanna Franca, additional, Minicucci, Fabio, additional, Giacalone, Giacomo, additional, Falini, Andrea, additional, Falautano, Monica, additional, Rovere-Querini, Patrizia, additional, Roveri, Luisa, additional, and Filippi, Massimo, additional

Published
2022
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37. Physiotherapy with Dual-Tasks Improves Cognition and Resting-State Functional Connectivity in Parkinson’s Disease with Postural Instability and Gait Disorders (P1-1.Virtual)

Author

Leocadi, Michela, primary, Canu, Elisa, additional, Sarasso, Elisabetta, additional, Gardoni, Andrea, additional, Basaia, Silvia, additional, Castelnovo, Veronica, additional, Volontè, M. Antonietta, additional, Filippi, Massimo, additional, and Agosta, Federica, additional

Published
2022
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38. Resting state functional brain networks associated with emotion processing in frontotemporal lobar degeneration

Author

Canu, E, Calderaro, D, Castelnovo, V, Basaia, S, Magno, M, Riva, N, Magnani, G, Caso, F, Caroppo, P, Prioni, S, Villa, C, Pain, D, Mora, G, Tremolizzo, L, Appollonio, I, Poletti, B, Silani, V, Filippi, M, Agosta, F, Canu, Elisa, Calderaro, Davide, Castelnovo, Veronica, Basaia, Silvia, Magno, Maria Antonietta, Riva, Nilo, Magnani, Giuseppe, Caso, Francesca, Caroppo, Paola, Prioni, Sara, Villa, Cristina, Pain, Debora, Mora, Gabriele, Tremolizzo, Lucio, Appollonio, Ildebrando, Poletti, Barbara, Silani, Vincenzo, Filippi, Massimo, Agosta, Federica, Canu, E, Calderaro, D, Castelnovo, V, Basaia, S, Magno, M, Riva, N, Magnani, G, Caso, F, Caroppo, P, Prioni, S, Villa, C, Pain, D, Mora, G, Tremolizzo, L, Appollonio, I, Poletti, B, Silani, V, Filippi, M, Agosta, F, Canu, Elisa, Calderaro, Davide, Castelnovo, Veronica, Basaia, Silvia, Magno, Maria Antonietta, Riva, Nilo, Magnani, Giuseppe, Caso, Francesca, Caroppo, Paola, Prioni, Sara, Villa, Cristina, Pain, Debora, Mora, Gabriele, Tremolizzo, Lucio, Appollonio, Ildebrando, Poletti, Barbara, Silani, Vincenzo, Filippi, Massimo, and Agosta, Federica

Abstract

This study investigated the relationship between emotion processing and resting-state functional connectivity (rs-FC) of the brain networks in frontotemporal lobar degeneration (FTLD). Eighty FTLD patients (including cases with behavioral variant of frontotemporal dementia, primary progressive aphasia, progressive supranuclear palsy syndrome, motor neuron disease) and 65 healthy controls underwent rs-functional MRI. Emotion processing was tested using the Comprehensive Affect Testing System (CATS). In patients and controls, correlations were investigated between each emotion construct and rs-FC changes within critical networks. Mean rs-FC of the clusters significantly associated with CATS scoring were compared among FTLD groups. FTLD patients had pathological CATS scores compared with controls. In controls, increased rs-FC of the cerebellar and visuo-associative networks correlated with better scores in emotion-matching and discrimination tasks, respectively; while decreased rs-FC of the visuo-spatial network was related with better performance in the affect-matching and naming. In FTLD, the associations between rs-FC and CATS scores involved more brain regions, such as orbitofrontal and middle frontal gyri within anterior networks (i.e., salience and default-mode), parietal and somatosensory regions within visuo-spatial and sensorimotor networks, caudate and thalamus within basal-ganglia network. Rs-FC changes associated with CATS were similar among all FTLD groups. In FTLD compared to controls, the pattern of rs-FC associated with emotional processing involves a larger number of brain regions, likely due to functional specificity loss and compensatory attempts. These associations were similar across all FTLD groups, suggesting a common physiopathological mechanism of emotion processing breakdown, regardless the clinical presentation and pattern of atrophy.

Published
2022

39. Stepwise connectivity paves the way to reveal functional network vulnerability in age‐related neurodegenerative disorders

Author

Filippi, Massimo, Basaia, Silvia, Cividini, Camilla, Edoardo Gioele Spinelli, Castelnovo, Veronica, Leocadi, Michela, Calderaro, Davide, Canu, Elisa, and Agosta, Federica

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2021

42. Amyotrophic Lateral Sclerosis–Frontotemporal Dementia

Author

Cividini, Camilla, primary, Basaia, Silvia, additional, Spinelli, Edoardo G., additional, Canu, Elisa, additional, Castelnovo, Veronica, additional, Riva, Nilo, additional, Cecchetti, Giordano, additional, Caso, Francesca, additional, Magnani, Giuseppe, additional, Falini, Andrea, additional, Filippi, Massimo, additional, and Agosta, Federica, additional

Published
2021
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45. Brain architecture changes across the FTLD spectrum

Author

Cividini, Camilla, primary, Agosta, Federica, additional, Basaia, Silvia, additional, Spinelli, Edoardo Gioele, additional, Castelnovo, Veronica, additional, Canu, Elisa, additional, Riva, Nilo, additional, Magnani, Giuseppe, additional, Caso, Francesca, additional, and Filippi, Massimo, additional

Published
2021
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