Clinical care of patients with amyotrophic lateral sclerosis

Radunović, Aleksandar; Mitsumoto, Hiroshi; Leigh, P. Nigel

doi:10.1016/s1474-4422(07)70244-2

Cited by 142 publications

(96 citation statements)

References 134 publications

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“…Rilutek (riluzole; Sanofi-Aventis, Bridgewater, NJ), the popular "antiglutamatergic" agent, remains the only Food and Drug Administration (FDA) approved drug for ALS treatment at present, decreasing the progression of ALS, and increasing the survival of ALS patients by 4 -19 months (Radunovic et al, 2007). However, riluzole may not be effective during advanced stages of the disease (Radunovic et al, 2007). Memantine, a noncompetitive Nmethyl-D-aspartate receptor antagonist, was recently found to prolong the survival of SOD1…”

Section: A Multidrug Therapy For the Treatment Of Alsmentioning

confidence: 99%

Lactate dyscrasia: a novel explanation for amyotrophic lateral sclerosis

Meethal

Atwood

2012

Neurobiology of Aging

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Amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease) is a progressive debilitating neurodegenerative disease with no cure. We propose a novel molecular model for the pathogenesis of ALS that involves an adenosine triphosphate (ATP)-dependent muscle neuronal lactate shuttle (MNLS) at the neuromuscular junction (NMJ) to regulate the flow of lactate from muscle to neurons and vice versa. Failure of the MNLS due to respiratory chain dysfunction is proposed to result in lactate toxicity and degeneration of nerve endings at the NMJ leading to nerve terminus dysjunction from the muscle cell. At a critical threshold where denervation outpaces reinnervation, a vicious cycle is established where the remaining innervated muscle fibers are required to work harder to compensate for normal function, and in so doing produce toxic lactate concentrations which induces further denervation and neuronal death. This mechanism explains the exponential progression of ALS leading to paralysis. The molecular events leading to the dysregulation of the MNLS and the dismantling of NMJ are explained in the context of known ALS familial mutations and age-related endocrine dyscrasia. Combination drug therapies that inhibit lactate accumulation at the NMJ, enhance respiratory chain function, and/or promote reinnervation are predicted to be effective therapeutic strategies for ALS. Published by Elsevier Inc.

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Section: A Multidrug Therapy For the Treatment Of Alsmentioning

confidence: 99%

Lactate dyscrasia: a novel explanation for amyotrophic lateral sclerosis

Meethal

Atwood

2012

Neurobiology of Aging

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“…Additionally, HCPs may have differing approaches to existing guidelines and conflicting opinions regarding the appropriate timing of an intervention [34] and discussions concerning NIV and gastrostomy are often initiated too late with little time for patients to discuss their preferences or for decisions to be unhurried [35,36]. Nonetheless, the provision of information by HCPs has been found to be instrumental in patients' treatment decisions [37,38].…”

Section: Introductionmentioning

confidence: 99%

Accepting or declining non-invasive ventilation or gastrostomy in amyotrophic lateral sclerosis: patients’ perspectives

et al. 2015

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word count: 174 words 2 ABSTRACTThe objective was to identify factors associated with decisions made by patients with Amyotrophic Lateral Sclerosis (ALS) to accept or decline non-invasive ventilation (NIV) and/or gastrostomy in a prospective population-based study.Twenty-one people with ALS, recruited from the South-East ALS Register who made an intervention decision during the study timeframe underwent a face-to-face in-depth interview, with or without their informal caregiver present.Sixteen had accepted an intervention (11 accepted gastrostomy, four accepted NIV and one accepted both interventions). Five patients had declined gastrostomy. Thematic analysis revealed three main themes: i) patientcentric factors (including perceptions of control, acceptance and need, and aspects of fear); ii) external factors (including roles played by healthcare professionals, family, and information provision); and iii) the concept of time (including living in the moment and the notion of 'right thing, right time'). Many aspects of these factors were interrelated. Decision-making processes for the patients were found to be complex and multifaceted and reinforce arguments for individualised (rather than 'algorithm-based') approaches to facilitating decision-making by people with ALS who require palliative interventions.3

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“…Notwithstanding the aforementioned effects on respiratory symptoms, quality of life, and survival many studies suggest that the employment of NIPPV in ALS is poor worldwide (Bourke et al, 2002;Lechtzin et al, 2004), with a need for more education of clinicians and patients regarding the benefits of mechanical ventilation earlier in the course of the disease (Bradley et al, 2001). The reasons for such low uptake of NIPPV treatment are multifactorial but are influenced by differences in the experience of physicians, its availability and cost, uncertainty of the benefits and timing for starting ventilation, and concerns that ventilatory support might prolong suffering, render home care less feasible, and lead to dependency or ventilator entrapment (Radunović et al, 2007). Moreover, there is still debate about the optimal timing to introduce ventilation in these patients and whether early NIPPV initiation could actually lead to increased survival rates.…”

Section: Non-invasive Mechanical Ventilationmentioning

confidence: 99%

“…In fact oxygen therapy may reduce respiratory drive particularly during sleep and has been associated with CO 2 retention and a less favourable outcome than ventilation (Bach et al, 1998;Gay & Edmonds, 1995). At present, worldwide accepted guidelines propose NIPPV initiation in the presence of respiratory symptoms, and/or evidence of respiratory muscles weakness (FVC ≤ 80% of predicted or SNIP ≤ 40 cmH 2 O), evidence of significant nocturnal desaturation on overnight oximetry (< 90% for > 5% of the time asleep) or a morning arterial PaCO 2 > 6.5 kPa (Radunović et al, 2007;Miller et al, 2009a).…”

Section: Non-invasive Mechanical Ventilationmentioning

confidence: 99%

“…Another study, however, failed to show any benefit in loss of lung function or mortality in 9 patients with ALS (Chaisson et al, 2006). A part from sustaining respiration with mechanical devices, special consideration should be given to prevention of aspiration and development of pneumonia (Radunović et al, 2007;Miller et al, 2009 a,b). In this regard, it is of fundamental importance the reduction of the amount of salivary secretions through the use of several medications (such as amitriptyline and botulinum toxin injections), devoting adequate amount of time in teaching proper swallowing technique, and maintaining hydration.…”

Section: Physiotherapy and Management Of Airway Secretionsmentioning

confidence: 99%

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