Motor neuron disease beginning with frontotemporal dementia: clinical features and progression

Gromicho, Marta; Kuźma‐Kozakiewicz, Magdalena; Szacka, Katarzyna; Nieporęcki, Krzysztof; Andersen, Peter M.; Großkreutz, Julian; Petri, Susanne; Pinto, Susana; Uysal, Hilmi; Swash, Michael; Carvalho, Mamede de

doi:10.1080/21678421.2021.1910309

Cited by 8 publications

(4 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, a considerable, and extremely variable, delay between the two diseases was found – being higher for “PPA-first” patients (median: 24 months) than for “MND-first” ones (median: 12 months). Such findings partially align with a recent investigation ( Gromicho et al, 2021 ) reporting a median delay of 1 year between the onset of bvFTD and MN dysfunction in FTD-MND patients.…”

Section: Discussionsupporting

confidence: 91%

“…FTD-like cognitive and behavioral dysfunctions indeed occur in up to 50% of MND patients ( Strong et al, 2017 ), 5–15% of whom showing a full-blown FTD ( Montuschi et al, 2015 ). However, such a spectrum can be also “read backward” – i.e., as “FTD-MND” ( Strong et al, 2017 ): evidence of upper (UMN) and/or lower motor neuron (LMN) dysfunction can be in fact detected in up to 30% of FTD patients ( Burrell et al, 2011 ; Cerami et al, 2015 ; Gromicho et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Primary progressive aphasia and motor neuron disease: A review

Aiello

Feroldi

Luca

et al. 2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

BackgroundThis study aims at reviewing, within the framework of motor neuron disease-frontotemporal degeneration (MND-FTD)-spectrum disorders, evidence on the co-occurrence between primary progressive aphasia (PPA) and MND in order to profile such a complex at pathological, genetic and clinical levels.MethodsThis review was pre-registered (osf.io/ds8m4) and performed in accordance with the 2020 PRISMA guidelines. Case reports/series and group studies were included if addressing (1) progressive non-fluent aphasia (PNFA) or semantic dementia (SD) with MND or (2) MND patients with co-morbid PNFA/SD.ResultsOut of 546 initial records, 56 studies were included. As to case reports/series (N = 35), which included 61 PPA-MND patients, the following findings yielded: (1) PNFA is more frequent than SD in PPA-MND; (2) in PPA-MND, the most prevalent motor phenotypes are amyotrophic lateral sclerosis and predominant-upper MND, with bulbar involvement being ubiquitous; (3) extrapyramidal features are moderately frequent in PPA-MND; (4) PPA-MND patients usually display frontotemporal, left-greater-than-right involvement; (5) TDP-43-B is the typical pathological substrate of PPA-MND; (6) TBK1 mutations represent the most frequent genetic risk factors for PPA-MND.As to group studies, including 121 patients, proportional meta-analytic procedures revealed that: (1) the lifetime prevalence of MND in PPA is 6%; (2) PPA occurs in 19% of patients with co-morbid MND and FTD; (3) MND is more frequent in PNFA (10%) than in SD patients (3%).DiscussionInsights herewith delivered into the clinical, neuropathological and genetic features of PPA-MND patients prompt further investigations aimed at improving clinical practice within the MND-FTD spectrum.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Primary progressive aphasia and motor neuron disease: A review

Aiello

Feroldi

Luca

et al. 2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

show abstract

“…Distal upper-limb weakness, sometimes with no upper motor neuron signs, is also frequently observed in patients meeting the criteria for ALS-FTD ( 51 ). Other reports link the development of bulbar symptoms during the disease course with cognitive and behavioral symptoms ( 52 , 53 ). Interestingly, other studies have also reported a higher presence of abnormal oculomotor findings, extrapyramidal signs, and autonomic dysfunction in patients with ALS and having prominent bulbar symptoms at disease onset ( 54 ).…”

Section: Extra-motor Involvement In Alsmentioning

confidence: 97%

Pathophysiological Underpinnings of Extra-Motor Neurodegeneration in Amyotrophic Lateral Sclerosis: New Insights From Biomarker Studies

et al. 2022

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) lie at opposing ends of a clinical, genetic, and neuropathological continuum. In the last decade, it has become clear that cognitive and behavioral changes in patients with ALS are more frequent than previously recognized. Significantly, these non-motor features can impact the diagnosis, prognosis, and management of ALS. Partially overlapping neuropathological staging systems have been proposed to describe the distribution of TAR DNA-binding protein 43 (TDP-43) aggregates outside the corticospinal tract. However, the relationship between TDP-43 inclusions and neurodegeneration is not absolute and other pathophysiological processes, such as neuroinflammation (with a prominent role of microglia), cortical hyperexcitability, and synaptic dysfunction also play a central role in ALS pathophysiology. In the last decade, imaging and biofluid biomarker studies have revealed important insights into the pathophysiological underpinnings of extra-motor neurodegeneration in the ALS-FTLD continuum. In this review, we first summarize the clinical and pathophysiological correlates of extra-motor neurodegeneration in ALS. Next, we discuss the diagnostic and prognostic value of biomarkers in ALS and their potential to characterize extra-motor neurodegeneration. Finally, we debate about how biomarkers could improve the diagnosis and classification of ALS. Emerging imaging biomarkers of extra-motor neurodegeneration that enable the monitoring of disease progression are particularly promising. In addition, a growing arsenal of biofluid biomarkers linked to neurodegeneration and neuroinflammation are improving the diagnostic accuracy and identification of patients with a faster progression rate. The development and validation of biomarkers that detect the pathological aggregates of TDP-43 in vivo are notably expected to further elucidate the pathophysiological underpinnings of extra-motor neurodegeneration in ALS. Novel biomarkers tracking the different aspects of ALS pathophysiology are paving the way to precision medicine approaches in the ALS-FTLD continuum. These are essential steps to improve the diagnosis and staging of ALS and the design of clinical trials testing novel disease-modifying treatments.

show abstract

“…Based on this large dataset, several papers were published so far, describing the influence of environment and lifestyle factors on ALS onset and progression (Kuraszkiewicz et al 2018;Korner et al 2019), risk factors for polyneuropathy in ALS (de Carvalho et al 2020), the patterns of disease presentation (Prell et al 2020;Gromicho et al 2020;Gromicho et al 2021;Matos et al 2020), diagnostic pathway of ALS patients (Campos et al 2021(Campos et al , 2023, the rate of disease progression (Prell, 2020;Barc et al 2020), the possible biomarkers (Hertel et al 2022), the impact of comorbidities (Diekmann et al 2020;Pereira et al 2021), the predictive impact of C9Orf72 mutation in respiratory decline (Miltenberger-Miltenyi et al 2019), family history of neurodegenerative diseases (Campos et al, 2020), influence of ALS on fertility (Uysal et al 2021), association of the contact sports with ALS (Henriques et al 2023), as well as potential predictive measures (Kuraszkiewicz et al 2020). METHONTOLOGY (Fernández-López et al 1997) is a method of ontology building that is grounded in software engineering methodologies.…”

Section: Ontology-based Web Database For Understanding Als (Onwebduals)mentioning

confidence: 99%

DALSO: domain ALS ontology

Podsiadły-Marczykowska,

Andersen,

Gromicho

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is an incurable, rapidly progressive neurodegenerative disease. During the course of ALS, virtually all skeletal muscles are gradually affected, including the respiratory muscles, and the disease is usually fatal within 2–5 years of symptom onset. Unequivocal and conclusive tests for ALS do not exist, its disease etiology is still unknown, and therapeutic options are limited. This paper presents the ALS domain ontology (DALSO), model containing formalized, semantic descriptions of a wide range of modeled disease related notions such as patient demographics, clinical findings and history, disease clinical features and diagnostic classifications, risk factors, genetics and pathophysiological mechanisms of motor neuron degeneration. The DALSO’s aim and information scope, design assumption, structure and implementation details are also described. DALSO covers the broad range of significant biomedical concepts ranging from clinical to molecular feature of the modeled disease, it represents a comprehensive, structured knowledge source for the ALS disease domain. To the best of authors’ knowledge, the DALSO is the first attempt to develop a formal, computational model representing knowledge of this fatal motor neuron disease. It provides the means for integrating and annotating clinical and research data, not only at the generic domain knowledge level, but also at the level of individual patient case studies. The DALSO is expressed in OWL2 language, contains 910 classes, is consistent and free of logical errors. Its syntactic correctness was validated by the Fact++ reasoner.

show abstract

Motor neuron disease beginning with frontotemporal dementia: clinical features and progression

Cited by 8 publications

References 43 publications

Primary progressive aphasia and motor neuron disease: A review

Primary progressive aphasia and motor neuron disease: A review

Pathophysiological Underpinnings of Extra-Motor Neurodegeneration in Amyotrophic Lateral Sclerosis: New Insights From Biomarker Studies

DALSO: domain ALS ontology

Contact Info

Product

Resources

About