Abnormal metabolic covariance patterns associated with multiple system atrophy and progressive supranuclear palsy

Tomše, Petra; Rebec, Eva; Studen, Andrej; Perovnik, Matej; Rus, Tomaž; Ležaič, Luka; Tang, Chris C.; Eidelberg, David; Trošt, Maja

doi:10.1016/j.ejmp.2022.04.016

Cited by 11 publications

(11 citation statements)

References 34 publications

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“…Several other neurodegenerative disorders may be subdivided into subtypes with different topographical metabolic profiles. Recent studies of multiple system atrophy [41] and progressive supranuclear palsy [42] have shown that the expression of a corresponding pattern is elevated in these patients regardless of disease subtype. As indicated by our results, the same may be true for sCJD.…”

Section: Discussionmentioning

confidence: 99%

Sporadic Creutzfeldt–Jakob disease is associated with reorganization of metabolic connectivity in a pathological brain network

Rus

Mlakar

Ležaič

et al. 2023

Euro J of Neurology

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Background and purpose: Although sporadic Creutzfeldt-Jakob disease (sCJD) is a rare cause of dementia, it is critical to understand its functional networks as the prion protein spread throughout the brain may share similar mechanisms with other more common neurodegenerative disorders. In this study, the metabolic brain network associated with sCJD was investigated and its internal network organization was explored. Methods:We explored 2-[ 18 F]fluoro-2-deoxyd-glucose positron emission tomography (FDG-PET) brain scans of 29 sCJD patients, 56 normal controls (NCs) and 46 other dementia patients from two independent centers. sCJD-related pattern (CJDRP) was identified in a cohort of 16 pathologically proven sCJD patients and 16 age-matched NCs using scaled subprofile modeling/principal component analysis and was prospectively validated in an independent cohort of 13 sCJD patients and 20 NCs. The pattern's specificity was tested on other dementia patients and its clinical relevance by clinical correlations. The pattern's internal organization was further studied using graph theory methods. Results:The CJDRP was characterized by relative hypometabolism in the bilateral caudate, thalami, middle and superior frontal gyri, parietal lobe and posterior cingulum in association with relative hypermetabolism in the hippocampi, parahippocampal gyri and cerebellum. The pattern's expression significantly discriminated sCJD from NCs and other dementia patients (p < 0.005; receiver operating characteristic analysis CJD vs. NCs area under the curve [AUC] 0.90-0.96, sCJD vs. Alzheimer's disease AUC 0.78, sCJD vs. behavioral variant of frontotemporal dementia AUC 0.84). The pattern's expression significantly correlated with cognitive, functional decline and disease duration. The metabolic connectivity analysis revealed inefficient information transfer with specific network reorganization. Conclusions:The CJDRP is a robust metabolic biomarker of sCJD. Due to its excellent clinical correlations it has the potential to monitor disease in emerging disease-modifying trials.

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Section: Discussionmentioning

confidence: 99%

Sporadic Creutzfeldt–Jakob disease is associated with reorganization of metabolic connectivity in a pathological brain network

Rus

Mlakar

Ležaič

et al. 2023

Euro J of Neurology

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“…The classification of CBS in that study was, however, poor, due to the lack of a specific atrophic pattern and greater overlap with other neurodegenerative syndromes in that cohort. Patterns of both brainstem and cortical hypometabolism can also aid in the differentiation of PSP-RS from the parkinsonian disorders, multiple system atrophy (MSA) and Parkinson's disease (PD) [11]. Visual assessment of patterns of hypometabolism performed well in another study, providing 90% accuracy to differentiate clinically diagnosed PSP from CBS, MSA and PD [12].…”

Section: Improving Imaging-based Differential Diagnosismentioning

confidence: 96%

Clinical and neuroimaging features of the progressive supranuclear palsy- corticobasal degeneration continuum

Whitwell

2023

Current Opinion in Neurology

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Purpose of review The aim of this study was to discuss how recent work has increased our understanding of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). The investigation of large and autopsy-confirmed cohorts, imaging modalities to assess different aspects of pathophysiology, clinical phenotypes and the application of advanced machine learning techniques, have led to recent advances in the field that will be discussed. Recent findings Literature over the past 18 months will be discussed under the following themes: studies assessing how different neuroimaging modalities can improve the diagnosis of PSP and CBD from other neurodegenerative and parkinsonian disorders, including the investigation of pathological targets such as tau, iron, neuromelanin and dopamine and cholinergic systems; work improving our understanding of clinical, neuroanatomical and pathological heterogeneity in PSP and CBD; and work using advanced neuroimaging tools to investigate patterns of disease spread, as well as biological mechanisms potentially driving spread through the brain in PSP and CBD. Summary The findings help improve the imaging-based diagnosis of PSP and CBD, allow more targeted prognostic estimates for patients accounting for phenotype or disease, and will aid in the development of appropriate and better-targeted disease biomarkers for clinical treatment trials.

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“…Most of the works refer to PSP without indicating subtypes, or are based on the examination of patients with PSP-RS. A study comparing abnormalities of brain metabolism in PSP and MSA revealed hypometabolism in the cerebellum and putamen in MSA and in the medial prefrontal cortices, nucleus caudatus, frontal cortices, and mesencephalon in PSP [ 11 ]. A different work presented decreased frontal and midbrain glucose metabolism as the neuroimaging features of PSP [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

The Assessment of Subregions in the Frontal Lobe May Be Feasible in the Differential Diagnosis of Progressive Supranuclear Palsy—Parkinsonism Predominant (PSP-P) and Multiple System Atrophy (MSA)

et al. 2022

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Progressive Supranuclear Palsy—Parkinsonism Predominant (PSP-P) is associated with moderate responsiveness to levodopa treatment and a possible lack of typical PSP milestones. The clinical manifestation of PSP-P poses difficulties in neurological examination. In the early stages it is often misdiagnosed as Parkinson’s Disease, and in the more advanced stages PSP-P shows more symptoms in common with Multiple System Atrophy—Parkinsonian type (MSA-P). The small number of tools enabling differential diagnosis of PSP-P and MSA leads to the necessity of searching for parameters facilitating in vivo diagnosis. In this study, 14 patients with PSP-P and 21 patients with MSA-P were evaluated using Single Photon Emission Computed Tomography. Considering the fact that PSP is linked with frontal deficits, regions of the frontal lobe were assessed in the context of hypoperfusion and their possible usefulness in the differential diagnosis with MSA-P. The outcome of the work revealed that the right middle frontal gyrus was the region most significantly affected in PSP-P.

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Abnormal metabolic covariance patterns associated with multiple system atrophy and progressive supranuclear palsy

Cited by 11 publications

References 34 publications

Sporadic Creutzfeldt–Jakob disease is associated with reorganization of metabolic connectivity in a pathological brain network

Sporadic Creutzfeldt–Jakob disease is associated with reorganization of metabolic connectivity in a pathological brain network

Clinical and neuroimaging features of the progressive supranuclear palsy- corticobasal degeneration continuum

The Assessment of Subregions in the Frontal Lobe May Be Feasible in the Differential Diagnosis of Progressive Supranuclear Palsy—Parkinsonism Predominant (PSP-P) and Multiple System Atrophy (MSA)

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