Testing the diagnostic accuracy of [18F]FDG-PET in discriminating spinal- and bulbar-onset amyotrophic lateral sclerosis

Sala, Arianna; Iaccarino, Leonardo; Fania, Piercarlo; Vanoli, Emilia Giovanna; Fallanca, Federico; Pagnini, Caterina; Cerami, Chiara; Calvo, Andrea; Canosa, Antonio; Pagani, Marco; Chiò, Adriano; Cistaro, Angelina; Perani, Daniela

doi:10.1007/s00259-018-4246-2

Cited by 27 publications

(25 citation statements)

References 71 publications

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“…This finding suggests that the area of synaptic loss in bulbar onset ALS patients is more widespread than that in spinal onset ALS patients. An 18 F‐FDG‐PET study found hypometabolism in the right dorsomedial region of the primary motor cortex (foot/leg region) for spinal onset patients and in the right ventrolateral region of the primary motor cortex (face/head region) for bulbar onset ALS patients [42]. However, no similar finding was found in our study.…”

Section: Discussioncontrasting

confidence: 67%

Detection of changes in synaptic density in amyotrophic lateral sclerosis patients using ¹⁸F‐SynVesT‐1 positron emission tomography

Tang

Liu

et al. 2022

Euro J of Neurology

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Background and purpose: Synaptic loss is well established as the major correlate of characteristic and consistent pathology in amyotrophic lateral sclerosis (ALS). We aimed to assess the possible discriminant diagnostic value of 18 F-SynVesT-1 positron emission tomography (PET) as a marker of ALS pathology and investigate whether specific synaptic density signatures are present in ALS with different subtypes.Methods: Twenty-one patients with ALS and 25 healthy controls (HCs) were recruited.All participants underwent 18 F-SynVesT-1-PET. Synaptic density between ALS and HCs and between different ALS subgroups were compared. Correlation between synaptic density and clinical features in ALS was also analyzed.Results: Low uptake distribution was found in the group comprising 21 ALS patients as compared with HCs in the right temporal lobe and the bilateral inferior frontal gyrus, anterior cingulate, and hippocampus-insula region. We also found low uptake in the bilateral superior temporal gyrus, hippocampus-insula, anterior cingulate, and left inferior frontal gyrus in ALS patients with cognitive impairment compared to HCs. Furthermore, compared to spinal onset ALS, bulbar onset ALS showed low uptake in the bilateral cingulate gyrus and high uptake in the bilateral superior temporal gyrus and left occipital lobe.No significant result was found in correlation analysis.

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Section: Discussioncontrasting

confidence: 67%

Detection of changes in synaptic density in amyotrophic lateral sclerosis patients using ¹⁸F‐SynVesT‐1 positron emission tomography

Tang

Liu

et al. 2022

Euro J of Neurology

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“…Of note, previous 18 F‐FDG PET studies consistently reported, in both sporadic and genetic ALS cases, along with motor cortical and frontal hypometabolism, a relative increase in glucose metabolism in the brainstem and cerebellum 77,78 . An increase in cerebral metabolism was found also in the occipital 79–81 and temporal regions 82,83 . A possible explanation for these metabolic increases relies on the presence of activated microglia or reactive astrocytes in the same regions, which has been shown in regions of neuronal dysfunction in inherited ALS 84 .…”

Section: Discussionmentioning

confidence: 78%

¹¹C‐PK11195 PET–based molecular study of microglia activation in SOD1 amyotrophic lateral sclerosis

Tondo

Iaccarino

Cerami

et al. 2020

Ann Clin Transl Neurol

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Objective Neuroinflammation is considered a key driver for neurodegeneration in several neurological diseases, including amyotrophic lateral sclerosis (ALS). SOD1 mutations cause about 20% of familial ALS, and related pathology might generate microglial activation triggering neurodegeneration. 11C‐PK11195 is the prototypical and most validated PET radiotracer, targeting the 18‐kDa translocator protein which is overexpressed in activated microglia. In this study, we investigated microglia activation in asymptomatic (ASYM) and symptomatic (SYM) SOD1 mutated carriers, by using 11C‐PK11195 and PET imaging. Methods We included 20 subjects: 4 ASYM‐carriers, neurologically normal, 6 SYM‐carriers with probable ALS, and 10 healthy controls. A receptor parametric mapping procedure estimated 11C‐PK11195 binding potentials and voxel‐wise statistical comparisons were performed at group and single‐subject levels. Results Both the SYM‐ and ASYM‐carriers showed significant microglia activation in cortical and subcortical structures, with variable patterns at individual level. Clusters of activation were present in occipital and temporal regions, cerebellum, thalamus, and medulla oblongata. Notably, SYM‐carriers showed microglia activation also in supplementary and primary motor cortices and in the somatosensory regions. Interpretation In vivo neuroinflammation occurred in all SOD1 mutated cases since the presymptomatic stages, as shown by a significant cortical and subcortical microglia activation. The involvement of sensorimotor cortex became evident at the symptomatic disease stage. Although our data indicate the role of in vivo PET imaging for assessing resident microglia in the investigation of SOD1‐ALS pathophysiology, further studies are needed to clarify the temporal and spatial dynamics of microglia activation and its relationship with neurodegeneration.

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“…To this regard, the only available study using IRCA in the TDP-43 spectrum, specifically in amyotrophic lateral sclerosis, reported a positive association between metabolism in the midbrain and white matter in the corticospinal tract (Pagani et al, 2014). Still, results deriving from group-level metabolic connectivity analysis in amyotrophic lateral sclerosis should be interpreted with caution, as they might be affected by the intrinsic metabolic heterogeneity that characterizes this condition (Matías-Guiu et al, 2016; Sala et al, 2019). Further reflection on group inhomogeneity and molecular connectivity is reported in the last section of this review.…”

Section: Pet Molecular Connectivitymentioning

confidence: 99%

Brain Molecular Connectivity in Neurodegenerative Diseases: Recent Advances and New Perspectives Using Positron Emission Tomography

Sala

Perani

2019

Front. Neurosci.

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Positron emission tomography (PET) represents a unique molecular tool to get in vivo access to a wide spectrum of biological and neuropathological processes, of crucial relevance for neurodegenerative conditions. Although most PET findings are based on massive univariate approaches, in the last decade the increasing interest in multivariate methods has paved the way to the assessment of unexplored cerebral features, spanning from resting state brain networks to whole-brain connectome properties. Currently, the combination of molecular neuroimaging techniques with multivariate connectivity methods represents one of the most powerful, yet still emerging, approach to achieve novel insights into the pathophysiology of neurodegenerative diseases. In this review, we will summarize the available evidence in the field of PET molecular connectivity, with the aim to provide an overview of how these studies may increase the understanding of the pathogenesis of neurodegenerative diseases, over and above "traditional" structural/functional connectivity studies. Considering the available evidence, a major focus will be represented by molecular connectivity studies using [18F]FDG-PET, today applied in the major neuropathological spectra, from amyloidopathies and tauopathies to synucleinopathies and beyond. Pioneering studies using PET tracers targeting brain neuropathology and neurotransmission systems for connectivity studies will be discussed, their strengths and limitations highlighted with reference to both applied methodology and results interpretation. The most common methods for molecular connectivity assessment will be reviewed, with particular emphasis on the available strategies to investigate molecular connectivity at the singlesubject level, of potential relevance for not only research but also diagnostic purposes. Finally, we will highlight possible future perspectives in the field, with reference in particular to newly available PET tracers, which will expand the application of molecular connectivity to new, exciting, unforeseen possibilities.

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Testing the diagnostic accuracy of [18F]FDG-PET in discriminating spinal- and bulbar-onset amyotrophic lateral sclerosis

Cited by 27 publications

References 71 publications

Detection of changes in synaptic density in amyotrophic lateral sclerosis patients using ¹⁸F‐SynVesT‐1 positron emission tomography

Detection of changes in synaptic density in amyotrophic lateral sclerosis patients using ¹⁸F‐SynVesT‐1 positron emission tomography

¹¹C‐PK11195 PET–based molecular study of microglia activation in SOD1 amyotrophic lateral sclerosis

Brain Molecular Connectivity in Neurodegenerative Diseases: Recent Advances and New Perspectives Using Positron Emission Tomography

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Testing the diagnostic accuracy of [18F]FDG-PET in discriminating spinal- and bulbar-onset amyotrophic lateral sclerosis

Cited by 27 publications

References 71 publications

Detection of changes in synaptic density in amyotrophic lateral sclerosis patients using 18F‐SynVesT‐1 positron emission tomography

Detection of changes in synaptic density in amyotrophic lateral sclerosis patients using 18F‐SynVesT‐1 positron emission tomography

11C‐PK11195 PET–based molecular study of microglia activation in SOD1 amyotrophic lateral sclerosis

Brain Molecular Connectivity in Neurodegenerative Diseases: Recent Advances and New Perspectives Using Positron Emission Tomography

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Detection of changes in synaptic density in amyotrophic lateral sclerosis patients using ¹⁸F‐SynVesT‐1 positron emission tomography

Detection of changes in synaptic density in amyotrophic lateral sclerosis patients using ¹⁸F‐SynVesT‐1 positron emission tomography

¹¹C‐PK11195 PET–based molecular study of microglia activation in SOD1 amyotrophic lateral sclerosis