Spectroscopic markers of neurodegeneration in the mesial prefrontal cortex predict survival in ALS

Hanstock, Chris; Sun, Kerry; Choi, Changho; Eurich, Dean T.; Camicioli, Richard; Johnston, Wendy; Kalra, Sanjay

doi:10.1080/21678421.2020.1727926

Cited by 9 publications

(9 citation statements)

References 40 publications

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“…The findings of the present study are consistent with previous studies, where shorter survival times have been linked with reduced FVC, increased age and lower ALSFRS‐R scores [16, 39, 40]. Importantly, a primary and replication cohort were used between which inconsistent results were found with regard to the clinical features that contributed significantly to the survival model.…”

Section: Discussionsupporting

confidence: 89%

“…In the motor cortex, reductions in NAA/choline in the motor cortex have been linked with shorter survival time [11]. Similarly, reduced NAA/myo‐inositol in the mesial prefrontal region is associated with survival over a 2‐year observation period [16]. Using DTI, fractional anisotropy of the CST was associated with survival 3 years after [15].…”

Section: Discussionmentioning

confidence: 99%

“…Degeneration in the motor region was the primary focus of the study; however, extramotor pathology has been previously associated with survival in ALS [16, 17]. Similarly, frontotemporal‐related cognitive impairment has been linked with poorer survival outcomes [40].…”

Section: Discussionmentioning

confidence: 99%

“…As surrogate markers of neurodegeneration, imaging metrics have been explored for prognostic use. Here, in vivo degeneration in the upper motor neuron (UMN) system [10–15] and frontotemporal regions [12, 16, 17] have been closely associated with survival in previous studies.…”

Section: Introductionmentioning

confidence: 99%

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Severity of in vivo corticospinal tract degeneration is associated with survival in amyotrophic lateral sclerosis: a longitudinal, multicohort study

Ishaque

Elamy

et al. 2023

Euro J of Neurology

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Background and purpose This study sought to evaluate the relationship of progressive corticospinal tract (CST) degeneration with survival in patients with amyotrophic lateral sclerosis (ALS). Methods Forty‐one ALS patients and 42 healthy controls were prospectively recruited from the Canadian ALS Neuroimaging Consortium. Magnetic resonance imaging scanning and clinical evaluations were performed on participants at three serial visits with 4‐month intervals. Texture analysis was performed on T1‐weighted magnetic resonance imaging scans and the texture feature ‘autocorrelation’ was quantified. Whole‐brain group‐level comparisons were performed between patient subgroups. Linear mixed models were used to evaluate longitudinal progression. Region‐of‐interest and 3D voxel‐wise Cox proportional‐hazards regression models were constructed for survival prediction. For all survival analyses, a second independent cohort was used for model validation. Results Autocorrelation of the bilateral CST was increased at baseline and progressively increased over time at a faster rate in ALS short survivors. Cox proportional‐hazards regression analyses revealed autocorrelation of the CST as a significant predictor of survival at 5 years follow‐up (hazard ratio 1.28, p = 0.005). Similarly, voxel‐wise whole‐brain survival analyses revealed that increased autocorrelation of the CST was associated with shorter survival. ALS patients stratified by median autocorrelation in the CST had significantly different survival times using the Kaplan–Meier curve and log‐rank tests (χ2 = 7.402, p = 0.007). Conclusions Severity of cerebral degeneration is associated with survival in ALS. CST degeneration progresses faster in subgroups of patients with shorter survival. Neuroimaging holds promise as a tool to improve patient management and facilitation of clinical trials.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Severity of in vivo corticospinal tract degeneration is associated with survival in amyotrophic lateral sclerosis: a longitudinal, multicohort study

Ishaque

Elamy

et al. 2023

Euro J of Neurology

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“…Although NAA serum levels after ILB ® treatment were still 2.4 times higher than the values recorded in controls, a 41.7% decrease compared to pre-treatment levels was detected. Previous clinical studies have demonstrated that brain levels of NAA in patients with ALS are significantly lower than those of healthy subjects [ 26 , 27 , 28 ] and correlates negatively with time of patients’ survival [ 29 ]. Furthermore, in a mouse model of selective motoneuronal loss, mimicking the primary pathology associated with ALS, we have very recently found a dramatic depletion of NAA in spinal cord extracts [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

ILB® Attenuates Clinical Symptoms and Serum Biomarkers of Oxidative/Nitrosative Stress and Mitochondrial Dysfunction in Patients with Amyotrophic Lateral Sclerosis

Lazzarino

Mangione

Belli

et al. 2021

JPM

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Oxidative/nitrosative stress and mitochondrial dysfunction is a hallmark of amyotrophic lateral sclerosis (ALS), an invariably fatal progressive neurodegenerative disease. Here, as an exploratory arm of a phase II clinical trial (EudraCT Number 2017-005065-47), we used high performance liquid chromatography(HPLC) to investigate changes in the metabolic profiles of serum from ALS patients treated weekly for 4 weeks with a repeated sub-cutaneous dose of 1 mg/kg of a proprietary low molecular weight dextran sulphate, called ILB®. A significant normalization of the serum levels of several key metabolites was observed over the treatment period, including N-acetylaspartate (NAA), oxypurines, biomarkers of oxidative/nitrosative stress and antioxidants. An improved serum metabolic profile was accompanied by significant amelioration of the patients’ clinical conditions, indicating a response to ILB® treatment that appears to be mediated by improvement of tissue bioenergetics, decrease of oxidative/nitrosative stress and attenuation of (neuro)inflammatory processes.

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Neuroimaging in genetic frontotemporal dementia and amyotrophic lateral sclerosis

Häkkinen

Chu

Lee

2020

Neurobiology of Disease

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Spectroscopic markers of neurodegeneration in the mesial prefrontal cortex predict survival in ALS

Cited by 9 publications

References 40 publications

Severity of in vivo corticospinal tract degeneration is associated with survival in amyotrophic lateral sclerosis: a longitudinal, multicohort study

Severity of in vivo corticospinal tract degeneration is associated with survival in amyotrophic lateral sclerosis: a longitudinal, multicohort study

ILB® Attenuates Clinical Symptoms and Serum Biomarkers of Oxidative/Nitrosative Stress and Mitochondrial Dysfunction in Patients with Amyotrophic Lateral Sclerosis

Neuroimaging in genetic frontotemporal dementia and amyotrophic lateral sclerosis

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