Edoardo Gioele Spinelli

• Doctor of Medicine
• Research Associate at San Raffaele Scientific Institute

The large-scale approval of anti-amyloid monoclonal antibodies for treating Alzheimer’s disease (AD) has raised concerns about their safety due to treatment-emergent amyloid-related imaging abnormalities (ARIA). We present two cases of patients diagnosed with mild cognitive impairment due to AD who were enrolled in the GRADUATE I clinical trial. Th...

Background Previous EEG studies highlighted the potential of analyzing neural oscillatory activity for differentially diagnosing Alzheimer’s disease (AD) and frontotemporal dementia (FTD). We recently studied primary progressive aphasia (PPA) variants associated with AD and FTD, revealing distinctive patterns of alterations in linear lagged connect...

Background This study aims at applying the AT(N) classification to a cohort of patients with Alzheimer’s disease (AD) and related disorders, and to investigate how many cases would be eligible for the emerging disease‐modifying treatments. Method We conducted a retrospective evaluation of 429 patients referred to the Memory Center of IRCCS San Raf...

The ability to predict the pathology spreading in patients with frontotemporal dementia (FTD) is crucial for early diagnosis and targeted interventions. This study examined the relationship between network vulnerability and longitudinal atrophy progression in FTD patients, using Network Diffusion Model (NDM) of pathology spread. Thirty behavioural-...

Background and Purpose Precise and timely diagnosis is crucial for the optimal use of emerging disease‐modifying treatments for Alzheimer disease (AD). Electroencephalography (EEG), which is noninvasive and cost‐effective, can capture neural abnormalities linked to various dementias. This study explores the use of individual alpha frequency (IAF) d...

Multifactorial models integrating brain variables at multiple scales are warranted to investigate aging and its relationship with neurodegeneration. Our aim was to evaluate how aging affects functional connectivity of pivotal regions of the human brain connectome (i.e., hubs), which represent potential vulnerability ‘stations’ to aging, and whether...

Objectives A significant overlap between amyotrophic lateral sclerosis (ALS) and behavioral variant of frontotemporal dementia (bvFTD) has been observed at clinical, genetic and pathological levels. Within this continuum of presentations, the presence of mild cognitive and/or behavioral symptoms in ALS patients has been consistently reported, altho...

Objective: To investigate structural and functional neural organization in amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS) and progressive muscular atrophy (PMA) patients. Methods: 173 ALS, 38 PLS, 28 PMA sporadic patients and 79 healthy controls were recruited from three Italian centers. Subjects underwent clinical, neurops...

Background and aims Considering the great heterogeneity of amyotrophic lateral sclerosis (ALS), the identification of accurate prognostic predictors is fundamental for both the clinical practice and the design of treatment trials. This study aimed to explore the progression of clinical and structural brain changes in patients with ALS, and to asses...

Objective: To understand whether the clinical phenotype of nonfluent/agrammatic primary progressive aphasia (nfvPPA) could present differences depending on the patient's native language. Methods: In this cross-sectional study, we analyzed connected speech samples in monolingual English (nfvPPA-E) and Italian speakers (nfvPPA-I) who were diagnose...

In the last few decades, brain functional connectivity (FC) has been extensively assessed using resting-state functional magnetic resonance imaging (RS-fMRI), which is able to identify temporally correlated brain regions known as RS functional networks. Fundamental insights into the pathophysiology of several neurodegenerative conditions have been...

We describe a patient, previously known for NMOSD, who presented a rapidly progressive worsening of muscle strength, respiratory, and bulbar functions. ALS associated with cognitive impairment was diagnosed, while genetic analysis revealed a hexanucleotide repeat expansion in the C9orf72 gene. To the best of our knowledge, this is the first reporte...

The extent of central nervous system involvement in Kennedy's disease (KD) relative to other motor neuron disease (MND) phenotypes still needs to be clarified. In this study, we investigated cortical and white matter (WM) MRI alterations in 25 patients with KD, compared with 24 healthy subjects, 25 patients with sporadic amyotrophic lateral scleros...

Motor neuron disease (MND) is a fatal progressive neurodegenerative disorder characterized by the breakdown of the motor system. The clinical spectrum of MND encompasses different phenotypes classified according to the relative involvement of the upper or lower motor neurons (LMN) and the presence of genetic or cognitive alterations, with clear pro...

Background and purpose This study aimed to assess the predictive value of multimodal brain magnetic resonance imaging (MRI) on survival in a large cohort of patients with motor neuron disease (MND), in combination with clinical and cognitive features. Methods Two hundred MND patients were followed‐up prospectively for a median of 4.13 years. At ba...

Objective: To determine the added value of multimodal structural magnetic resonance imaging (MRI) to language assessment in the differential diagnosis of primary progressive aphasia (PPA) variants. Methods: 59 PPA patients [29 nonfluent (nfvPPA), 15 semantic (svPPA), 15 logopenic (lvPPA)] and 38 healthy controls underwent 3D T1-weighted and diff...

Background After the demonstration of a corticoefferent propagation pattern in amyotrophic lateral sclerosis (ALS) by neuropathological studies, this concept has been used for in vivo staging of individual patients by diffusion tensor imaging (DTI) techniques, both in `classical` ALS and in restricted phenotypes such as primary lateral sclerosis (P...

Background: No reliable indicators of the transition to the progressive course in multiple sclerosis (MS) have been identified so far. The main clinical feature of the progressive phase of MS is usually impairment of walking. Magnetic resonance imaging and optical coherence tomography have emerged recently as promising tools to assess increasing n...

Introduction: Several neuroimaging techniques have been used to define in vivo markers of pathological alterations underlying amyotrophic lateral sclerosis (ALS). Growing evidence supports the use of magnetic resonance imaging (MRI) and positron emission tomography (PET) for the non-invasive detection of central nervous system involvement in patien...

Objective: To explore structural and functional changes of the brain and cervical cord in patients with amyotrophic lateral sclerosis (ALS) due to mutation in the superoxide dismutase (SOD1) gene compared with sporadic ALS. Methods: Twenty patients with SOD1 ALS, 11 with sporadic ALS, and 33 healthy controls underwent clinical evaluation and bra...

Importance The ability to predict the pathology underlying different neurodegenerative syndromes is of critical importance owing to the advent of molecule-specific therapies. Objective To determine the rates of positron emission tomography (PET) amyloid positivity in the main clinical variants of primary progressive aphasia (PPA). Design, Setting...

Background The criteria for assessing upper motor neuron pathology in pure lower motor neuron disease (LMND) still remain a major issue of debate with respect to the clinical classification as an amyotrophic lateral sclerosis (ALS) variant. Objective The study was designed to investigate white matter damage by a hypothesis-guided tract-of-interest...

Supplementary tables

This prospective study developed an MRI-based method for identification of individual motor neuron disease (MND) patients and test its accuracy at the individual patient level in an independent sample compared with mimic disorders. 123 patients with amyotrophic lateral sclerosis (ALS), 44 patients with predominantly upper motor neuron disease (PUMN...

This study investigated structural and functional MRI abnormalities in C9orf72 motor neuron disease (MND) relative to disease severity-matched sporadic MND cases. We enrolled 19 C9orf72 and 67 disease severity-matched sporadic MND patients, and 22 controls. Sporadic cases were grouped in patients with: no cognitive/behavioural deficits (sporadic-mo...

Background We performed an observational study of laughter during seminaturalistic conversations between patients with dementia and familial caregivers. Patients were diagnosed with (1) behavioural variant frontotemporal dementia (bvFTD), (2) right temporal variant frontotemporal dementia (rtFTD), (3) semantic variant of primary progressive aphasia...

Objective: To characterize in vivo signatures of pathological diagnosis in a large cohort of patients with primary progressive aphasia (PPA) variants defined by current diagnostic classification. Methods: Extensive clinical, cognitive, neuroimaging, and neuropathological data were collected from 69 patients with sporadic PPA, divided into 29 sem...

Our understanding of the biology of language has begun to evolve beyond the focal lesion-based model of classical aphasiology, mostly owing to the emergence of novel neuroimaging techniques that are able to detect even subtle structural and functional abnormalities in a wide range of neurological disorders, including conditions primarily affecting...

Purpose To investigate the patterns of cortical thinning and white matter tract damage in patients with lower motor neuron (LMN)-predominant disease compared with healthy control subjects and those with classic amyotrophic lateral sclerosis (ALS) and to evaluate the relationship between brain structural changes and clinical and cognitive features i...

Objective: To assess the structural correlates of cognitive and behavioral impairment in motor neuron diseases (MND) using multimodal MRI. Methods: One hundred one patients with sporadic MND (56 classic amyotrophic lateral sclerosis, 31 upper motor neuron phenotype, and 14 lower motor neuron phenotype) and 51 controls were enrolled. Patients wer...

Structural imaging, which should be performed at least once in the diagnostic work up of patients with cognitive impairment, serves to exclude other, potentially treatable, diseases, and to identify specific findings useful in distinguishing different forms of neurodegenerative dementia. Diffusion tensor imaging (DTI) is sensitive to detecting whit...

Purpose: To assess brachial plexus magnetic resonance (MR) imaging features and limb-girdle muscle abnormalities as signs of muscle denervation in patients with amyotrophic lateral sclerosis (ALS). Materials and methods: This study was approved by the local ethical committees on human studies, and written informed consent was obtained from all s...

Crossed aphasia has been reported mainly as post-stroke aphasia resulting from brain damage ipsilateral to the dominant right hand. Here, we described a case of a crossed nonfluent/agrammatic primary progressive aphasia (nfvPPA), who developed a corticobasal syndrome (CBS). We collected clinical, cognitive, and neuroimaging data for four consecutiv...

Purpose: To investigate whether specific patterns of brain gray matter (GM) regional volumes and white matter (WM) microstructural abnormalities and spinal cord atrophy occur in patients with pure and complicated hereditary spastic paraplegias (HSPs). Relationships between clinical and cognitive features of patients with HSP who had brain and cerv...

Objectives: We have described cerebrospinal fluid (CSF) myeloid microvesicles (MVs) as a marker of microglia activation during neuroinflammation in Alzheimer disease (AD), and characterized their ability to produce toxic amyloid β1-42 (Aβ1-42 ) oligomers from aggregated or soluble substrate. The aim of this study is to investigate the association...

Little is known about the longitudinal changes of brain damage in patients with sporadic nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) and in Progranulin (GRN) mutation carriers. This study reports the clinical and MRI longitudinal data of a patient with nfvPPA carrying GRN Cys157LysfsX97 mutation (GRN +). Voxel-based morphom...

White matter (WM) tract alterations were assessed in patients with progressive supranuclear palsy (PSP) relative to healthy controls and patients with idiopathic Parkinson's disease (PD) to explore the relationship of WM tract damage with clinical disease severity, performance on cognitive tests, and apathy. 37 PSP patients, 41 PD patients, and 34...

White matter (WM) microstructural damage and its relationship with cortical abnormalities were explored in early-onset Alzheimer's disease (EOAD) compared with late-onset AD (LOAD) patients. Structural and diffusion tensor magnetic resonance images were obtained from 22 EOAD patients, 35 LOAD patients, and 40 healthy controls. Patterns of WM micros...

In multiple sclerosis (MS), physical and cognitive deficits not only reflect structural damage, but also functional imbalance in and between brain networks. Resting-state functional magnetic resonance imaging (fMRI) allows one to investigate intrinsic, synchronized brain activity across the whole brain, and to measure the degree of functional corre...