Combinatory Biomarker Use of Cortical Thickness, MUNIX, and ALSFRS-R at Baseline and in Longitudinal Courses of Individual Patients With Amyotrophic Lateral Sclerosis

Wirth, A.; Khomenko, Andrei; Baldaranov, Dobri; Kobor, Ines; Hsam, Ohnmar; Grimm, Thomas W.; Johannesen, Siw; Bruun, Tim‐Henrik; Schulte‐Mattler, Wilhelm J.; Greenlee, Mark W.; Bogdahn, Ulrich

doi:10.3389/fneur.2018.00614

Cited by 20 publications

(16 citation statements)

References 56 publications

(112 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MUNE was positively correlated with the MRC score and the clinical dysfunction measured by the ALSFRS-R scale. This finding was in agreement with other researchers, although using MUNIX instead of MUNE as a measure [23,24]. MUNE is calculated by dividing the maximal CMAP amplitude by the mean surface SMUP [25].…”

Section: Discussionsupporting

confidence: 92%

Motor unit number estimation versus compound muscle action potential in the evaluation of motor unit loss in amyotrophic lateral sclerosis

Ibrahem

Al-Mahdawi

Hamdan

2021

Egypt J Neurol Psychiatry Neurosurg

View full text Add to dashboard Cite

Introduction Motor neuron loss is the primary pathologic feature of amyotrophic lateral sclerosis (ALS). An estimate of the number of surviving motor units (MUs) represents a direct measure of the disease state in ALS. The objective of the study is to compare MU number estimation (MUNE) using the multipoint stimulation method (MPS) and compound muscle action potentials (CMAP) amplitude in patients with ALS. Methods Twenty-eight patients with ALS with a disease duration of 3–48 months were studied. Nerve conduction study of the median, ulnar, tibial, common peroneal, and sural nerves were done. Besides, electromyography (EMG) of cranio-bulbar, cervical, thoracic and lumbosacral muscles, and MPS-MUNE. Results MUNE is decreased in patients with ALS. MUNE was positively correlated with CMAP amplitude, medical research council (MRC) scale, and ALS functional rating scale (ALS-FRS). On the contrary, MUNE was negatively correlated with MUAP duration. Case detection by the MUNE methods was high as compared to that of CMAP amplitude. Conclusions MUNE is highly specific and more sensitive than CMAP amplitude in detecting the neurophysiologic abnormalities in patients with ALS. Case detection by MUNE is three times more than CMAP amplitudes. The rate of decline of motor units using the MPS-MUNE is more sensitive than the MRC score and ALSFRS-R when expressed as the percentage change from baseline.

show abstract

Section: Discussionsupporting

confidence: 92%

Motor unit number estimation versus compound muscle action potential in the evaluation of motor unit loss in amyotrophic lateral sclerosis

Ibrahem

Al-Mahdawi

Hamdan

2021

Egypt J Neurol Psychiatry Neurosurg

View full text Add to dashboard Cite

show abstract

“…Because ALS is a clinically heterogeneous condition with considerable variation in survival times, accurate prognostic indicators are urgently needed . We showed that the simulated aggregation levels based on early imaging data can help to predict survival of individual patients in a large dataset of ALS patients.…”

Section: Discussionmentioning

confidence: 98%

Connectome‐Based Propagation Model in Amyotrophic Lateral Sclerosis

Meier

Burgh

Nitert

et al. 2020

Annals of Neurology

View full text Add to dashboard Cite

Objective: Clinical trials in amyotrophic lateral sclerosis (ALS) continue to rely on survival or functional scales as endpoints, despite the emergence of quantitative biomarkers. Neuroimaging-based biomarkers in ALS have been shown to detect ALS-associated pathology in vivo, although anatomical patterns of disease spread are poorly characterized. The objective of this study is to simulate disease propagation using network analyses of cerebral magnetic resonance imaging (MRI) data to predict disease progression. Methods: Using brain networks of ALS patients (n = 208) and matched controls across longitudinal time points, network-based statistics unraveled progressive network degeneration originating from the motor cortex and expanding in a spatiotemporal manner. We applied a computational model to the MRI scan of patients to simulate this progressive network degeneration. Simulated aggregation levels at the group and individual level were validated with empirical impairment observed at later time points of white matter and clinical decline using both internal and external datasets. Results: We observe that computer-simulated aggregation levels mimic true disease patterns in ALS patients. Simulated patterns of involvement across cortical areas show significant overlap with the patterns of empirically impaired brain regions on later scans, at both group and individual levels. These findings are validated using an external longitudinal dataset of 30 patients. Interpretation: Our results are in accordance with established pathological staging systems and may have implications for patient stratification in future clinical trials. Our results demonstrate the utility of computational models in ALS to predict disease progression and underscore their potential as a prognostic biomarker.

show abstract

“…Possible direct effects of G-CSF upon the CNS were not assessed, as we did not obtain post-mortem analysis of deceased patients. Neuroimaging studies conducted on our G-CSF treated patient cohort ( 77 ) did not directly address possible G-CSF related structural effects—we also had no patient control group without G-CSF treatment. One indirect mode of action by which G-CSF exerts neuroprotective effects may be through polarization of the immune system toward an anti-inflammatory state ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

Biomarker Supervised G-CSF (Filgrastim) Response in ALS Patients

Johannesen

Budeus²,

Peters

et al. 2018

Front. Neurol.

Self Cite

View full text Add to dashboard Cite

Objective: To evaluate safety, tolerability and feasibility of long-term treatment with Granulocyte-colony stimulating factor (G-CSF), a well-known hematopoietic stem cell factor, guided by assessment of mobilized bone marrow derived stem cells and cytokines in the serum of patients with amyotrophic lateral sclerosis (ALS) treated on a named patient basis.Methods: 36 ALS patients were treated with subcutaneous injections of G-CSF on a named patient basis and in an outpatient setting. Drug was dosed by individual application schemes (mean 464 Mio IU/month, range 90-2160 Mio IU/month) over a median of 13.7 months (range from 2.7 to 73.8 months). Safety, tolerability, survival and change in ALSFRS-R were observed. Hematopoietic stem cells were monitored by flow cytometry analysis of circulating CD34+ and CD34+CD38− cells, and peripheral cytokines were assessed by electrochemoluminescence throughout the intervention period. Analysis of immunological and hematological markers was conducted.Results: Long term and individually adapted treatment with G-CSF was well tolerated and safe. G-CSF led to a significant mobilization of hematopoietic stem cells into the peripheral blood. Higher mobilization capacity was associated with prolonged survival. Initial levels of serum cytokines, such as MDC, TNF-beta, IL-7, IL-16, and Tie-2 were significantly associated with survival. Continued application of G-CSF led to persistent alterations in serum cytokines and ongoing measurements revealed the multifaceted effects of G-CSF.Conclusions: G-CSF treatment is feasible and safe for ALS patients. It may exert its beneficial effects through neuroprotective and -regenerative activities, mobilization of hematopoietic stem cells and regulation of pro- and anti-inflammatory cytokines as well as angiogenic factors. These cytokines may serve as prognostic markers when measured at the time of diagnosis. Hematopoietic stem cell numbers and cytokine levels are altered by ongoing G-CSF application and may potentially serve as treatment biomarkers for early monitoring of G-CSF treatment efficacy in ALS in future clinical trials.

show abstract

Combinatory Biomarker Use of Cortical Thickness, MUNIX, and ALSFRS-R at Baseline and in Longitudinal Courses of Individual Patients With Amyotrophic Lateral Sclerosis

Cited by 20 publications

References 56 publications

Motor unit number estimation versus compound muscle action potential in the evaluation of motor unit loss in amyotrophic lateral sclerosis

Motor unit number estimation versus compound muscle action potential in the evaluation of motor unit loss in amyotrophic lateral sclerosis

Connectome‐Based Propagation Model in Amyotrophic Lateral Sclerosis

Biomarker Supervised G-CSF (Filgrastim) Response in ALS Patients

Contact Info

Product

Resources

About