What do we know about the variability in survival of patients with amyotrophic lateral sclerosis?

McCombe, Pamela A.; Garton, Fleur; Katz, Matthew H.; Wray, Naomi R.; Henderson, Robert D.

doi:10.1080/14737175.2020.1785873

Cited by 13 publications

(7 citation statements)

References 326 publications

(304 reference statements)

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“…In patients with FALS, the symptoms usually appear earlier (approximately 5 years) than in those diagnosed with SALS, a fact apparently related to Mendelian gene variants lowering the age of onset [5]. The mean survival from the first symptom is 3-5 years, although approximately 10% of patients live longer than 10 years [6]. The reasons for this exceptional survival remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

NAD+ Precursors and Antioxidants for the Treatment of Amyotrophic Lateral Sclerosis

et al. 2021

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Charcot first described amyotrophic lateral sclerosis (ALS) between 1865 and 1874 as a sporadic adult disease resulting from the idiopathic progressive degeneration of the motor neuronal system, resulting in rapid, progressive, and generalized muscle weakness and atrophy. There is no cure for ALS and no proven therapy to prevent it or reverse its course. There are two drugs specifically approved for the treatment of ALS, riluzol and edaravone, and many others have already been tested or are following clinical trials. However, at the present moment, we still cannot glimpse a true breakthrough in the treatment of this devastating disease. Nevertheless, our understanding of the pathophysiology of ALS is constantly growing. Based on this background, we know that oxidative stress, alterations in the NAD+-dependent metabolism and redox status, and abnormal mitochondrial dynamics and function in the motor neurons are at the core of the problem. Thus, different antioxidant molecules or NAD+ generators have been proposed for the therapy of ALS. This review analyzes these options not only in light of their use as individual molecules, but with special emphasis on their potential association, and even as part of broader combined multi-therapies.

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Section: Introductionmentioning

confidence: 99%

NAD+ Precursors and Antioxidants for the Treatment of Amyotrophic Lateral Sclerosis

et al. 2021

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“…Thus far, research in these areas has been applied primarily to healthy aging and to (preclinical) Alzheimer’s disease (AD), where education, lifestyle or behavioral modifications (e.g., intellectual engagement throughout the lifespan, physical activity) explain a large proportion of the variance in cognition [ 13 , 14 ]. In ALS, there is an urgent need to clarify similar factors and mechanisms of resistance and resilience, which might allow for new preventive and therapeutic strategies for this incurable neurodegenerative disorder, which is currently limited to palliative treatment [ 15 , 16 ].…”

Section: Vascular Health For Reservementioning

confidence: 99%

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Schreiber

Bernal

Ulbrich

et al. 2023

Cells

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Brain vascular health appears to be critical for preventing the development of amyotrophic lateral sclerosis (ALS) and slowing its progression. ALS patients often demonstrate cardiovascular risk factors and commonly suffer from cerebrovascular disease, with evidence of pathological alterations in their small cerebral blood vessels. Impaired vascular brain health has detrimental effects on motor neurons: vascular endothelial growth factor levels are lowered in ALS, which can compromise endothelial cell formation and the integrity of the blood–brain barrier. Increased turnover of neurovascular unit cells precedes their senescence, which, together with pericyte alterations, further fosters the failure of toxic metabolite removal. We here provide a comprehensive overview of the pathogenesis of impaired brain vascular health in ALS and how novel magnetic resonance imaging techniques can aid its detection. In particular, we discuss vascular patterns of blood supply to the motor cortex with the number of branches from the anterior and middle cerebral arteries acting as a novel marker of resistance and resilience against downstream effects of vascular risk and events in ALS. We outline how certain interventions adapted to patient needs and capabilities have the potential to mechanistically target the brain microvasculature towards favorable motor cortex blood supply patterns. Through this strategy, we aim to guide novel approaches to ALS management and a better understanding of ALS pathophysiology.

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“…intellectual engagement throughout the lifespan, physical activity) explain a large proportion of the variance in cognition [13,14]. In ALS, there is an urgent need to clarify similar factors and mechanisms of resistance and resilience, which might allow for new preventive and therapeutic strategies for this incurable neurodegenerative disorder, which is currently limited to palliative treatment [15,16].…”

Section: Vascular Health For Reservementioning

confidence: 99%

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Schreiber¹,

Bernal²,

Ulbrich³

et al. 2023

Preprint

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Brain vascular health appears to be of critical importance for protection against the development of amyotrophic lateral sclerosis (ALS) as well as the slowing of disease progression. ALS patients often demonstrate cardiovascular risk factors and commonly suffer from cerebrovascular disease, with evidence of pathological alterations in the small cerebral vessels. Impaired vascular brain health has detrimental effects on motor neurons as lowered vascular endothelial growth factor levels compromise endothelial cell formation, promoting blood-brain barrier leakage and inflammation. Increased turnover of neurovascular unit cells precedes their senescence, which, together with pericyte alterations, further fosters the failure of toxic metabolite removal. We here provide a comprehensive overview of the pathogenesis of impaired brain vascular health in ALS and how novel magnetic resonance imaging techniques can aid its detection. In particular, we discuss vascular patterns of blood supply to the motor cortex with the number of branches from the anterior and middle cerebral arteries acting as a novel marker of resistance and resilience against downstream effects of vascular risk and events in ALS. We outline how certain interventions adapted to patient needs and capabilities have the potential to mechanistically target the brain microvasculature towards favorable motor cortex blood supply patterns. Through this strategy, we aim to guide novel approaches to ALS management and a better understanding of ALS pathophysiology.

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What do we know about the variability in survival of patients with amyotrophic lateral sclerosis?

Cited by 13 publications

References 326 publications

NAD+ Precursors and Antioxidants for the Treatment of Amyotrophic Lateral Sclerosis

NAD+ Precursors and Antioxidants for the Treatment of Amyotrophic Lateral Sclerosis

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

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