Article
Clinical Neurology
Hulya Ulugut, Simone Stek, Lianne E. E. Wagemans, Roos J. Jutten, Maria Antoinette Keulen, Femke H. Bouwman, Niels D. Prins, Afina W. Lemstra, Welmoed Krudop, Charlotte E. Teunissen, Bart N. M. van Berckel, Rik Ossenkoppele, Frederik Barkhof, Wiesje M. van der Flier, Philip Scheltens, Yolande A. L. Pijnenburg
Summary: Primary progressive aphasia (PPA) is divided into three prototypical subtypes - semantic, non-fluent, and logopenic - each subtype progresses differently over time and has a relatively long disease duration.
JOURNAL OF NEUROLOGY
(2022)
Article
Behavioral Sciences
Dario Saracino, Amandine Geraudie, Anne M. Remes, Sophie Ferrieux, Marie Nogues-Lassiaille, Simona Bottani, Lorenzo Cipriano, Marion Houot, Aurelie Funkiewiez, Agnes Camuzat, Daisy Rinaldi, Marc Teichmann, Jeremie Pariente, Philippe Couratier, Claire Boutoleau-Bretonniere, Sophie Auriacombe, Frederique Etcharry-Bouyx, Richard Levy, Raffaella Migliaccio, Eino Solje, Isabelle Le Ber
Summary: This study comprehensively analyzed 16 patients with PPA-C9orf72, revealing linguistic deficits and patterns of grey-matter atrophy. In addition to the common non-fluent/agrammatic variant, semantic and mixed forms of PPA were also observed. The study highlights the role of C9orf72 mutation in disrupting the anterior parts of the language network and provides guidelines for genetic testing in PPA patients.
Article
Clinical Neurology
M. -Marsel Mesulam, Christina A. Coventry, Eileen H. Bigio, Jaiashre Sridhar, Nathan Gill, Angela J. Fought, Hui Zhang, Cynthia K. Thompson, Changiz Geula, Tamar Gefen, Margaret Flanagan, Qinwen Mao, Sandra Weintraub, Emily J. Rogalski
Summary: Primary progressive aphasia is a neurodegenerative disease that selectively impairs language function. Autopsies and longitudinal studies have shown that primary progressive aphasia has various neuropathological changes, with Alzheimer's disease being the most common. Different variants of primary progressive aphasia have distinct neuropathological correlates, and word comprehension impairments are strong predictors of underlying neuropathology. Different types of primary progressive aphasia have different patterns of cortical atrophy, but all show severe damage to the left hemisphere language network. This study is important for understanding the neuropathological and clinical differences in primary progressive aphasia.
Article
Clinical Neurology
Allegra Kawles, Yasushi Nishihira, Alex Feldman, Nathan Gill, Grace Minogue, Rachel Keszycki, Christina Coventry, Callen Spencer, Jaclyn Lilek, Kaouther Ajroud, Giovanni Coppola, Rosa Rademakers, Emily Rogalski, Sandra Weintraub, Hui Zhang, Margaret E. Flanagan, Eileen H. Bigio, M-Marsel Mesulam, Changiz Geula, Qinwen Mao, Tamar Gefen
Summary: This study provides a detailed characterization of the pathological distribution of TDP-43 and gliosis in FTLD-TDP-type C, and investigates the relationship between inclusions and neurodegeneration. The findings suggest an inverse relationship between the extent of TDP-positive inclusions and neuronal loss.
Article
Clinical Neurology
Ignacio Illan-Gala, Victor Montal, Sergi Borrego-Ecija, Maria Luisa Mandelli, Neus Falgas, Ariane E. Welch, Jordi Pegueroles, Miguel Santos-Santos, Alexandre Bejanin, Daniel Alcolea, Oriol Dols-Icardo, Olivia Belbin, M. Belen Sanchez-Saudinos, Nuria Bargallo, Sofia Gonzalez-Ortiz, Albert Llado, Rafael Blesa, Bradford C. Dickerson, Howard J. Rosen, Bruce L. Miller, Alberto Lleo, Maria Luisa Gorno-Tempini, Raquel Sanchez-Valle, Juan Fortea
Summary: Cortical mean diffusivity shows promise as a sensitive biomarker for the study of the neurodegeneration-related microstructural changes in primary progressive aphasia (PPA). Increases in cortical mean diffusivity are correlated with cortical thinning and disease severity in PPA patients.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Review
Neurosciences
Davide Norata, Francesco Motolese, Alessandro Magliozzi, Fabio Pilato, Vincenzo Di Lazzaro, Simona Luzzi, Fioravante Capone
Summary: The semantic variant of primary progressive aphasia is a neurodegenerative disorder associated with frontotemporal lobar degeneration. Transcranial direct current stimulation shows promise as a potential non-pharmacological treatment for improving performance in patients with semantic variant primary progressive aphasia, although clinical trial results are inconsistent.
FRONTIERS IN HUMAN NEUROSCIENCE
(2023)
Article
Neurosciences
Joana Vitor, Dario Saracino, Sebastian Stroer, Agnes Camuzata, Karim Dorgham, Fabienne Clote, Philippe Martin-Hardya, Florence Pasquierf, Isabelle Le Ber
Summary: This study found that atypical white matter hyperintensities (WMH) in patients with GRN mutations causing frontotemporal dementia may impact levels of neuroaxonal damage markers, specifically neurofilament light chain (NfL). Patients with atypical WMH had significantly higher NfL levels compared to those without WMH, independent of age, disease duration, and Fazekas-Schmidt grade. The study suggests that considering WMH burden is important when evaluating NfL levels in GRN patients.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Clinical Neurology
Christopher R. S. Belder, Charles R. Marshall, Jessica Jiang, Salvatore Mazzeo, Anthipa Chokesuwattanaskul, Jonathan D. Rohrer, Anna Volkmer, Chris J. D. Hardy, Jason D. Warren
Summary: This article reviews recent progress in the diagnosis and management of primary progressive aphasia, the language-led dementias. It poses six key unanswered questions and suggests that linking proteinopathies to phenotypes may help resolve the clinical complexity of this disease.
JOURNAL OF NEUROLOGY
(2023)
Article
Immunology
Aitana Sogorb-Esteve, Imogen J. Swift, Ione O. C. Woollacott, Jason D. Warren, Henrik Zetterberg, Jonathan D. Rohrer
Summary: This study investigated the role of chemokines in primary progressive aphasias, revealing differential alterations in cerebrospinal fluid (CSF) and plasma across the PPA variants. The results suggest a potential role for neuroinflammation in these poorly understood sporadic disorders, indicating a potential therapeutic target for the future.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Neurosciences
Lucia A. A. Giannini, Claire Peterson, Daniel Ohm, Sharon X. Xie, Corey T. McMillan, Katya Raskovsky, Lauren Massimo, EunRah Suh, Vivianna M. Van Deerlin, David A. Wolk, John Q. Trojanowski, Edward B. Lee, Murray Grossman, David J. Irwin
Summary: Frontotemporal lobar degeneration proteinopathies with tau inclusions (FTLD-Tau) and TDP-43 inclusions (FTLD-TDP) show distinct severity and regional distribution of white matter and grey matter pathology, which may impact their clinical presentation.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Review
Clinical Neurology
Barbara Borroni, Caroline Graff, Orla Hardiman, Albert C. Ludolph, Fermin Moreno, Markus Otto, Marco Piccininni, Anne M. Remes, James B. Rowe, Harro Seelaar, Elka Stefanova, Latchezar Traykov, Giancarlo Logroscino
Summary: FRONTIERS is a European research study aimed at improving the understanding of FTLD-related disorders and their epidemiology, with the goal of promoting appropriate public health service policies and treatment strategies.
ALZHEIMERS & DEMENTIA
(2022)
Article
Cell Biology
Yanwei Wu, Wei Shao, Tiffany W. Todd, Jimei Tong, Mei Yue, Shunsuke Koga, Monica Castanedes-Casey, Ariston L. Librero, Chris W. Lee, Ian R. Mackenzie, Dennis W. Dickson, Yong-Jie Zhang, Leonard Petrucelli, Mercedes Prudencio
Summary: Loss-of-function mutations in the progranulin gene result in microglial activation and lysosomal dysfunction, leading to the accumulation of myelin debris and contributing to the pathogenesis of TDP-43 pathology.
Review
Clinical Neurology
Maria Carmela Tartaglia, Ian R. A. Mackenzie
Summary: Frontotemporal dementia is a devastating neurodegenerative condition for which there is currently no effective treatment. Recent molecular discoveries provide a foundation for the development of biomarkers and targeted therapies.
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2023)
Article
Neurosciences
David Foxe, Muireann Irish, Siddharth Ramanan, Samuel Stark, Nicholas J. Cordato, James R. Burrell, Olivier Piguet
Summary: This study found distinct profiles in behavior, mood, and functional capacity among different variants of Primary Progressive Aphasia (PPA), which go beyond the primary language disorder. Caregivers of semantic variant PPA reported greater behavioral disturbances than other variants, with memory problems also more severe in semantic and logopenic variants compared to non-fluent variant. These findings have important implications for clinical management and caregiver education in PPA.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2022)
Article
Immunology
Niels Hansen, Winfried Stoecker, Jens Wiltfang, Claudia Bartels, Kristin Rentzsch, Caroline Bouter
Summary: This study reports a case of svPPA associated with anti-glial fibrillary acid protein (GFAP) antibodies, expanding the clinical spectrum of svPPA and anti-GFAP-antibody related disease.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Neurosciences
Chiara Marzi, Alessandro d'Ambrosio, Stefano Diciotti, Alvino Bisecco, Manuela Altieri, Massimo Filippi, Maria Assunta Rocca, Loredana Storelli, Patrizia Pantano, Silvia Tommasin, Rosa Cortese, Nicola De Stefano, Gioacchino Tedeschi, Antonio Gallo
Summary: This study used machine learning techniques to assess the relationship between brain MRI structural volumes and cognitive deficits in MS patients, and found that damage to gray matter structures is most closely related to cognitive performance.
HUMAN BRAIN MAPPING
(2023)
Article
Clinical Neurology
Elisabetta Pagani, Loredana Storelli, Patrizia Pantano, Nikolaos Petsas, Gioacchino Tedeschi, Antonio Gallo, Nicola De Stefano, Marco Battaglini, Maria A. Rocca, Massimo Filippi
Summary: In patients with multiple sclerosis, the determination of brain atrophy in specific regions is clinically relevant. However, analyzing large datasets is challenging due to the increased variability in multicenter data. This study compared different methods to correct for center effects and investigated regional gray matter volume in patients with relapsing-remitting multiple sclerosis using a large multicenter dataset. The results showed that harmonization based on subsampling effectively reduced the residuals of the statistical model applied, and the multicenter results were more robust compared to findings from single-center analysis, highlighting the importance of data repositories from multiple centers.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Paolo Preziosa, Elisabetta Pagani, Alessandro Meani, Olga Marchesi, Lorenzo Conti, Andrea Falini, Maria A. Rocca, Massimo Filippi
Summary: Using diffusion tensor and neurite orientation dispersion and density imaging (NODDI), this study found that neuro-axonal damage and loss of microarchitecture integrity in focal WM lesions, NAWM, and GM contribute to cognitive impairment in MS.
JOURNAL OF NEUROLOGY
(2023)
Article
Neurosciences
Muhammad Abubakar Yamin, Paola Valsasina, Jacopo Tessadori, Massimo Filippi, Vittorio Murino, Maria A. Rocca, Diego Sona
Summary: Multiple sclerosis (MS) is a neurological condition characterized by brain damage and reorganization of brain networks. This article describes a system that uses machine learning to classify different MS phenotypes and identify relevant functional connections. The proposed framework shows significant classification performance for all MS phenotypes and successfully identifies relevant alterations in functional connectivity.
HUMAN BRAIN MAPPING
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Loredana Storelli, Elisabetta Pagani, Patrizia Pantano, Claudia Piervincenzi, Gioacchino Tedeschi, Antonio Gallo, Nicola De Stefano, Marco Battaglini, Maria A. Rocca, Massimo Filippi, INNI Network
Summary: This study compared different methods for measuring whole-brain and gray matter atrophy using the INNI dataset, and found that SPM-v12 and Jim-v8 software showed significant agreement in assessing gray matter volumes and atrophy progression.
JOURNAL OF MAGNETIC RESONANCE IMAGING
(2023)
Article
Clinical Neurology
Andrea Gardoni, Federica Agosta, Elisabetta Sarasso, Silvia Basaia, Elisa Canu, Michela Leocadi, Veronica Castelnovo, Andrea Tettamanti, Maria Antonietta Volonte, Massimo Filippi
Summary: This study aimed to assess cerebellar atrophy and activity alterations during functional MRI (fMRI) gait-simulating motor- and dual-tasks in Parkinson's disease patients with postural instability and gait disorders (PD-PIGD). The results showed that PD-PIGD patients had reduced volumes of cerebellar motor and non-motor areas and increased activity of cognitive areas during fMRI tasks. These findings suggest that the increased activity of non-motor cerebellar areas may be a compensatory mechanism in response to cerebellar motor dysfunction in PD-PIGD.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Massimo Filippi, Giordano Cecchetti, Annachiara Cagnin, Camillo Marra, Flavio Nobili, Lucilla Parnetti, Federica Agosta
Summary: Currently, no disease-modifying therapies are available for Alzheimer's disease (AD) in Europe. However, evidence from clinical trials suggests that anti-beta amyloid (Aβ) monoclonal antibodies (mAbs) may be authorized for marketing in the near future. A group of prominent AD clinical experts in Italy met to discuss patient selection and management strategies, recognizing the need for significant changes in dementia care to implement disease-modifying therapies. They emphasized the importance of a biological diagnosis using amyloid- and tau-related biomarkers, as well as specialized diagnostic work-up and exclusion criteria assessment by neurology specialists. The experts also proposed a reorganization of dementia and cognitive decline centers into three levels with defined tasks and requirements.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Matteo Azzimonti, Paolo Preziosa, Elisabetta Pagani, Paola Valsasina, Nicolo Tedone, Carmen Vizzino, Maria A. A. Rocca, Massimo Filippi
Summary: This study applied a longitudinal multiparametric MRI approach to investigate the mechanisms associated with cognitive worsening in MS patients. The results suggest that GM atrophy progression and functional impoverishment may be the main factors underlying cognitive worsening in MS.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Monica Margoni, Elisabetta Pagani, Paolo Preziosa, Mor Gueye, Matteo Azzimonti, Maria A. Rocca, Massimo Filippi
Summary: This study used multimodal MRI to investigate the regional distribution of different pathological processes in the brain white and gray matter of relapse-onset multiple sclerosis (MS) patients. The results showed that compared to healthy controls, relapsing-remitting MS (RRMS) patients exhibited white matter, deep gray matter, and cortical atrophy, as well as significantly lower MTR and T1w/T2w ratio in periventricular and infratentorial white matter, deep gray matter, and several cortical areas. Secondary progressive MS (SPMS) patients showed more severe deep gray matter and widespread cortical atrophy, lower MTR of periventricular white matter, deep gray matter, and cerebellum, lower T1w/T2w ratio of fronto-temporal white matter regions, lower ICV_f of some fronto-tempo-occipital white matter and cortical areas, and increased QSM and T1w/T2w ratio in the pallidum.
JOURNAL OF NEUROLOGY
(2023)
Correction
Clinical Neurology
Chiara Zanetta, Maria A. Rocca, Alessandro Meani, Vittorio Martinelli, Laura Ferre, Lucia Moiola, Massimo Filippi
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Luigi Albano, Silvia Basaia, Daniele Emedoli, Roberta Balestrino, Edoardo Pompeo, Lina Raffaella Barzaghi, Antonella Castellano, Andrea Falini, Sandro Iannaccone, Pietro Mortini, Massimo Filippi, Federica Agosta
Summary: This study aimed to assess the resting-state functional connectivity between thalamic ventral intermediate nucleus (Vim) and the rest of the brain before and after thalamotomy in Parkinson's disease (PD) patients. The results showed that the functional connectivity between Vim and visual areas increased before treatment and was restored after 1 year of treatment. Furthermore, the reduction in connectivity between left Vim and left visual cortex was associated with the improvement of tremor symptoms.
JOURNAL OF NEUROLOGY
(2023)
Review
Clinical Neurology
Andrea Gardoni, Elisabetta Sarasso, Federica Agosta, Massimo Filippi, Davide Corbetta
Summary: This study aims to investigate handwriting rehabilitation in people with Parkinson's disease (PD) and found that there is currently no consensus on the treatment and evaluation methods. Handwriting-specific training may have potential benefits for PD patients' handwriting, but further high-quality randomized controlled trials are needed to confirm this effect.
NEUROLOGICAL SCIENCES
(2023)
Article
Clinical Neurology
Valentina Pieri, Davide Gusmeo Curti, Rosina Paterra, Matteo Azzimonti, Giacomo Sferruzza, Giulia Berzero, Rosalinda Cardamone, Nicoletta Anzalone, Federica Agosta, Francesca Caso, Giuseppe Magnani, Gaetano Finocchiaro, Massimo Filippi
Summary: In this study, liquid biopsy diagnostic method successfully detected somatic mutations associated with gliomas in the patient's cerebrospinal fluid, providing therapeutically targetable mutations. This method can assist in the differential diagnosis of neurological diseases when imaging is not informative enough and surgical biopsy is not feasible.
NEUROLOGICAL SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Lorenzo Rampa, Roberto Santangelo, Carlo Gaspardone, Alice Cerutti, Giuseppe Magnani, Francesco Piscazzi, Giulia Sgherzi, Giorgio Fiore, Massimo Filippi, Federica Agosta, Alberto Margonato, Gabriele Fragasso
Summary: AChE-I treatment in patients with dementia may reduce the risk of cardiovascular events, particularly heart failure and myocardial revascularization. The use of AChE-I in dementia patients may be protective for cardiovascular outcomes.
AMERICAN JOURNAL OF CARDIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Massimo Filippi, Camilla Cividini, Silvia Basaia, Edoardo G. G. Spinelli, Veronica Castelnovo, Michela Leocadi, Elisa Canu, Federica Agosta
Summary: This study aimed to evaluate the impact of aging on the functional connectivity of pivotal regions in the human brain connectome and to examine whether these effects influence the overall functional and structural changes of the brain. By analyzing functional connectivity and cortical thinning data, it was found that aging leads to changes in functional connectivity of key regions and affects the structural alterations of specific brain regions.
MOLECULAR PSYCHIATRY
(2023)