Simultaneous PET-MRI Studies of the Concordance of Atrophy and Hypometabolism in Syndromic Variants of Alzheimer's Disease and Frontotemporal Dementia: An Extended Case Series

Background: Simultaneous PET-MRI is used to compare patterns of cerebral hypometabolism and atrophy in six different dementia syndromes. Objectives: The primary objective was to conduct an initial exploratory study regarding the concordance of atrophy and hypometabolism in syndromic variants of Alzheimer’s disease (AD) and frontotemporal dementia (FTD). The secondary objective was to determine the effect of image analysis methods on determination of atrophy and hypometabolism. Method: PET and MRI data were acquired simultaneously on 24 subjects with six variants of AD and FTD (n = 4 per group). Atrophy was rated visually and also quantified with measures of cortical thickness. Hypometabolism was rated visually and also quantified using atlas- and SPM-based approaches. Concordance was measured using weighted Cohen’s kappa. Results: Atrophy-hypometabolism concordance differed markedly between patient groups; kappa scores ranged from 0.13 (nonfluent/agrammatic variant of primary progressive aphasia, nfvPPA) to 0.49 (posterior cortical variant of AD, PCA). Heterogeneity was also observed within groups; the confidence intervals of kappa scores ranging from 0–0.25 for PCA to 0.29–0.61 for nfvPPA. More widespread MRI and PET changes were identified using quantitative methods than on visual rating. Conclusion: The marked differences in concordance identified in this initial study may reflect differences in the molecular pathologies underlying AD and FTD syndromic variants but also operational differences in the methods used to diagnose these syndromes. The superior ability of quantitative methodologies to detect changes on PET and MRI, if confirmed on larger cohorts, may favor their usage over qualitative visual inspection in future clinical diagnostic practic

Cortical markers of cognitive syndromes in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) can be associated with a spectrum of cognitive and behavioural symptoms, but the related patterns of focal cortical atrophy in non-demented ALS patients remain largely unknown. We enrolled 48 non-demented ALS patients and 26 healthy controls for a comprehensive neuropsychological assessment and a magnetic resonance exam. Behavioural and cognitive impairment was defined on the basis of a data-driven multi-domain approach in 21 ALS patients. Averaged cortical thickness of 74 bilateral brain regions was used as a measure of cortical atrophy. Cortical thinning in a fronto-parietal network, suggesting a disease-specific pattern of neurodegeneration, was present in all patients, independent of cognitive and behavioural status. Between-group and correlational analyses revealed that inferior frontal, temporal, cingular and insular thinning are markers for cognitive and behavioural deficits, with language impairment mainly related to left temporal pole and insular involvement. These specific correlates support the concept of a spectrum of deficits, with an overlap between the ALS cognitive phenotypes and the syndromes of frontotemporal dementia

The Effectiveness of Deep Brain Stimulation in Dystonia:A Patient-Centered Approach

Background: To systematically evaluate the effectiveness of deep brain stimulation of the globus pallidus internus (GPi-DBS) in dystonia on pre-operatively set functional priorities in daily living. Methods: Fifteen pediatric and adult dystonia patients (8 male; median age 32y, range 8-65) receiving GPi-DBS were recruited. All patients underwent a multidisciplinary evaluation before and 1-year post DBS implantation. The Canadian Occupational Performance Measure (COPM) first identified and then measured changes in functional priorities. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to evaluate dystonia severity. Results: Priorities in daily functioning substantially varied between patients but showed significant improvements on performance and satisfaction after DBS. Clinically significant COPM-score improvements were present in 7/8 motor responders, but also in 4/7 motor non-responders. Discussion: The use of a patient-oriented approach to measure GPi-DBS effectiveness in dystonia provides an unique insight in patients' priorities and demonstrates that tangible improvements can be achieved irrespective of motor response. Highlights: Functional priorities in life of dystonia patients and their caregivers vary greatlyThe effect of DBS on functional priorities did not correlate with motor outcomeHalf of the motor 'non-responder' patients reported important changes in their prioritiesThe effect of DBS in dystonia should not be measured by motor outcome alone

A Screening Tool to Quickly Identify Movement Disorders in Patients with Inborn Errors of Metabolism

Background: Movement disorders are frequent in patients with inborn errors of metabolism (IEMs) but poorly recognized, particularly by nonmovement disorder specialists. We propose an easy‐to‐use clinical screening tool to help recognize movement disorders. Objective: The aim is to develop a user‐friendly rapid screening tool for nonmovement disorder specialists to detect moderate and severe movement disorders in patients aged ≥4 years with IEMs. Methods: Videos of 55 patients with different IEMs were scored by experienced movement disorder specialists (n = 12). Inter‐rater agreements were determined on the presence and subtype of the movement disorder. Based on ranking and consensus, items were chosen to be incorporated into the screening tool. Results: A movement disorder was rated as present in 80% of the patients, with a moderate inter‐rater agreement (κ =0.420, P < 0.001) on the presence of a movement disorder. When considering only moderate and severe movement disorders, the inter‐rater agreement increased to almost perfect (κ = 0.900, P < 0.001). Dystonia was most frequently scored (27.3%) as the dominant phenotype. Treatment was mainly suggested for patients with moderate or severe movement disorders. Walking, observations of the arms, and drawing a spiral were found to be the most informative tasks and were included in the screening tool. Conclusions: We designed a screening tool to recognize movement disorders in patients with IEMs. We propose that this screening tool can contribute to select patients who should be referred to a movement disorder specialist for further evaluation and, if necessary, treatment of the movement disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Quantitative MRI Harmonization to Maximize Clinical Impact: The RIN–Neuroimaging Network

Neuroimaging studies often lack reproducibility, one of the cardinal features of the scientific method. Multisite collaboration initiatives increase sample size and limit methodological flexibility, therefore providing the foundation for increased statistical power and generalizable results. However, multisite collaborative initiatives are inherently limited by hardware, software, and pulse and sequence design heterogeneities of both clinical and preclinical MRI scanners and the lack of benchmark for acquisition protocols, data analysis, and data sharing. We present the overarching vision that yielded to the constitution of RIN-Neuroimaging Network, a national consortium dedicated to identifying disease and subject-specific in-vivo neuroimaging biomarkers of diverse neurological and neuropsychiatric conditions. This ambitious goal needs efforts toward increasing the diagnostic and prognostic power of advanced MRI data. To this aim, 23 Italian Scientific Institutes of Hospitalization and Care (IRCCS), with technological and clinical specialization in the neurological and neuroimaging field, have gathered together. Each IRCCS is equipped with high- or ultra-high field MRI scanners (i.e., ≥3T) for clinical or preclinical research or has established expertise in MRI data analysis and infrastructure. The actions of this Network were defined across several work packages (WP). A clinical work package (WP1) defined the guidelines for a minimum standard clinical qualitative MRI assessment for the main neurological diseases. Two neuroimaging technical work packages (WP2 and WP3, for clinical and preclinical scanners) established Standard Operative Procedures for quality controls on phantoms as well as advanced harmonized quantitative MRI protocols for studying the brain of healthy human participants and wild type mice. Under FAIR principles, a web-based e-infrastructure to store and share data across sites was also implemented (WP4). Finally, the RIN translated all these efforts into a large-scale multimodal data collection in patients and animal models with dementia (i.e., case study). The RIN-Neuroimaging Network can maximize the impact of public investments in research and clinical practice acquiring data across institutes and pathologies with high-quality and highly-consistent acquisition protocols, optimizing the analysis pipeline and data sharing procedures

Towards adaptive deep brain stimulation: clinical and technical notes on a novel commercial device for chronic brain sensing

Objective. Technical advances in deep brain stimulation (DBS) are crucial to improve therapeutic efficacy and battery life. We report the potentialities and pitfalls of one of the first commercially available devices capable of recording brain local field potentials (LFPs) from the implanted DBS leads, chronically and during stimulation. The aim was to provide clinicians with well-grounded tips on how to maximize the capabilities of this novel device, both in everyday practice and for research purposes. Approach. We collected clinical and neurophysiological data of the first 20 patients (14 with Parkinson's disease (PD), five with dystonia, one with chronic pain) that received the Percept (TM) PC in our centres. We also performed tests in a saline bath to validate the recordings quality. Main results. The Percept PC reliably recorded the LFP of the implanted site, wirelessly and in real time. We recorded the most promising clinically useful biomarkers for PD and dystonia (beta and theta oscillations) with and without stimulation. Furthermore, we provide an open-source code to facilitate export and analysis of data. Critical aspects of the system are presently related to contact selection, artefact detection, data loss, and synchronization with other devices. Significance. New technologies will soon allow closed-loop neuromodulation therapies, capable of adapting stimulation based on real-time symptom-specific and task-dependent input signals. However, technical aspects need to be considered to ensure reliable recordings. The critical use by a growing number of DBS experts will alert new users about the currently observed shortcomings and inform on how to overcome them.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

A screening tool to quickly identify movement disorders in patients with inborn errors of metabolism

BackgroundMovement disorders are frequent in patients with inborn errors of metabolism (IEMs) but poorly recognized, particularly by nonmovement disorder specialists. We propose an easy-to-use clinical screening tool to help recognize movement disorders.ObjectiveThe aim is to develop a user-friendly rapid screening tool for nonmovement disorder specialists to detect moderate and severe movement disorders in patients aged ≥4 years with IEMs.MethodsVideos of 55 patients with different IEMs were scored by experienced movement disorder specialists (n = 12). Inter-rater agreements were determined on the presence and subtype of the movement disorder. Based on ranking and consensus, items were chosen to be incorporated into the screening tool.ResultsA movement disorder was rated as present in 80% of the patients, with a moderate inter-rater agreement (κ =0.420, P P ConclusionsWe designed a screening tool to recognize movement disorders in patients with IEMs. We propose that this screening tool can contribute to select patients who should be referred to a movement disorder specialist for further evaluation and, if necessary, treatment of the movement disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Neurological Motor Disorder

Differential diagnosis of neurodegenerative dementias with the explainable MRI based machine learning algorithm MUQUBIA

Biomarker-based differential diagnosis of the most common forms of dementia is becoming increasingly important. Machine learning (ML) may be able to address this challenge. The aim of this study was to develop and interpret a ML algorithm capable of differentiating Alzheimer’s dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal control subjects based on sociodemographic, clinical, and magnetic resonance imaging (MRI) variables. 506 subjects from 5 databases were included. MRI images were processed with FreeSurfer, LPA, and TRACULA to obtain brain volumes and thicknesses, white matter lesions and diffusion metrics. MRI metrics were used in conjunction with clinical and demographic data to perform differential diagnosis based on a Support Vector Machine model called MUQUBIA (Multimodal Quantification of Brain whIte matter biomArkers). Age, gender, Clinical Dementia Rating (CDR) Dementia Staging Instrument, and 19 imaging features formed the best set of discriminative features. The predictive model performed with an overall Area Under the Curve of 98%, high overall precision (88%), recall (88%), and F1 scores (88%) in the test group, and good Label Ranking Average Precision score (0.95) in a subset of neuropathologically assessed patients. The results of MUQUBIA were explained by the SHapley Additive exPlanations (SHAP) method. The MUQUBIA algorithm successfully classified various dementias with good performance using cost-effective clinical and MRI information, and with independent validation, has the potential to assist physicians in their clinical diagnosis