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

ObjectivesWe 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 methodsA 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.ResultsAt 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 conclusionThe 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

Accounting for the impact of space policies: The case of the Italian Space Agency

The purpose of this work is assessing the impact of the Italian Space Agency (ASI) on the performance of the Italian space stakeholders through three specific policies, i.e. public procurement, public investment in Earth observation, and collaboration with the scientific community. This article explores multiple surveys targeting upstream and downstream companies, universities, and research centres in the space economy to estimates the cost-benefit ratio. We find that the socio-economic benefit of ASI policies is positive and, when considering upstream companies and downstream intermediate users in the field of Earth observation (EO), the impact is particularly high in the EO sector. The surveys show evidence of a positive effect of public procurement and EO data on the Italian space economy, both in terms of innovation and economic performance. Finally, we observe a significant impact of ASI also on the scientific community

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

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

Structural and functional brain connectome in motor neuron diseases: A multicenter MRI study

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, neuropsychological and brain MRI evaluations. Using graph analysis and connectomics, global and lobar topological network properties and regional structural and functional brain connectivity were assessed. The association between structural and functional network organization and clinical/cognitive data was investigated. Results: Compared to healthy controls, ALS and PLS patients showed altered structural global network properties, as well as local topological alterations and decreased structural connectivity in sensorimotor, basal ganglia, frontal and parietal areas. PMA patients showed preserved global structure. Patient groups did not show significant alterations of functional network topological properties relative to controls. Increased local functional connectivity was observed in ALS patients in the precentral, middle and superior frontal areas, and in PLS patients in the sensorimotor, basal ganglia and temporal networks. In both ALS and PLS patients, structural connectivity alterations correlated with motor impairment, while functional connectivity disruption was closely related to executive dysfunctions and behavioral disturbances. Conclusions: This multicenter study showed widespread motor/extra-motor network degeneration in ALS and PLS, suggesting that graph analysis and connectomics might represent a powerful approach to detect upper motor neuron degeneration, extra-motor brain changes and network reorganization associated with the disease. Network-based advanced MRI provides an objective in vivo assessment of motor neuron diseases, delivering potential prognostic markers

GABA-B1 Receptor-Null Schwann Cells Exhibit Compromised In Vitro Myelination

GABA-B receptors are important for Schwann cell (SC) commitment to a non-myelinating phenotype during development. However, the P0-GABA-B1fl/fl conditional knockout mice, lacking the GABA-B1 receptor specifically in SCs, also presented axon modifications, suggesting SC non-autonomous effects through the neuronal compartment. In this in vitro study, we evaluated whether the specific deletion of the GABA-B1 receptor in SCs may induce autonomous or non-autonomous cross-changes in sensory dorsal root ganglia (DRG) neurons. To this end, we performed an in vitro biomolecular and transcriptomic analysis of SC and DRG neuron primary cultures from P0-GABA-B1fl/fl mice. We found that cells from conditional P0-GABA-B1fl/fl mice exhibited proliferative, migratory and myelinating alterations. Moreover, we found transcriptomic changes in novel molecules that are involved in peripheral neuron-SC interaction