A Mouse Model of Pharyngeal Dysphagia in Amyotrophic Lateral Sclerosis

Lever, Teresa E.; Simon, Emmanuelle; Cox, Kathleen T.; Capra, Norman F.; O’Brien, Kevin F.; Hough, Monica Strauss; Murashov, Alexander K.

doi:10.1007/s00455-009-9232-1

Cited by 37 publications

(37 citation statements)

References 59 publications

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“…Further, the clinical presentation and progression of swallowing impairment and dysphagia in MND is heterogeneous – even between subtypes classic ALS, grouped by onset-type (i.e., bulbar- vs. spinal-onset). Several factors reported to influence or predict the severity and rate of progression of dysphagia in MND (particularly ALS), include: age at disease onset (i.e., older individuals often progress faster, require non-oral feeding sooner) [27–29], sex (i.e., females often present with bulbar symptoms earlier, and possibly greater severity) [27,30,31], and symptom onset (i.e., bulbar-onset ALS and PBP show faster rate of decline, different clinical presentation) [13,15,30,32,29]. Disease duration and the length of time since onset of bulbar symptoms have also been reported as prognostic indicators of function and severity [29,33].…”

Section: Discussionmentioning

confidence: 99%

Trends in Research Literature Describing Dysphagia in Motor Neuron Diseases (MND): A Scoping Review

et al. 2017

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Dysphagia in motor neuron diseases (MNDs) is highly complex, affecting all stages of swallowing and leading to impaired swallowing safety and efficiency. In order to explore the degree to which research is capturing the symptom of dysphagia in MND, we conducted a scoping review of the existing literature. The primary aims of this review were to identify common themes within the literature on dysphagia in MND, explore patterns and trends in research focus, and identify if any imbalances exist between the research themes related to dysphagia description and management. Methods A comprehensive search strategy yielded 1690 unique articles for review. Following relevance screening, a total of 157 articles were included in the synthesis. Relevant data and keywords were extracted from each article and grouped into themes. Frequency estimates were calculated for each theme to identify trends across research literature. Results Swallowing impairment in MNDs is described in a variety of ways across current research. The most commonly reported theme was Aspiration/Penetration, mentioned in 73.2% of all included articles; a significant imbalance was identified between reports of swallowing safety and efficiency (p=0.008). The most frequently reported theme related to dysphagia management was Enteral Nutrition, and very few studies have reported on the efficacy of Rehabilitation/Compensatory recommendations. Conclusions It is suggested that researchers and clinicians remain mindful of imbalances and gaps in research, and aim to characterize dysphagia in MNDs in a comprehensive manner. Further research investigating discrete, measureable changes in swallowing pathophysiology would be beneficial to delineate the key factors contributing to impaired swallowing safety and efficiency.

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Section: Discussionmentioning

confidence: 99%

Trends in Research Literature Describing Dysphagia in Motor Neuron Diseases (MND): A Scoping Review

et al. 2017

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“…Ceteris paribus is inherent in the design of the study. The SOD1-G93A transgenic rodents are validated models of oral-stage dysphagia for bulbar deficits of Amyotrophic Lateral Sclerosis [28, 32]. There are multiple models of Parkinson’s disease, including (6-OHDA)-induced DA depletion [8, 37], surgical lesions [42] and PINK KO genetic models [22, 23].…”

Section: Ceteris Paribus and Understanding Pathophysiologymentioning

confidence: 99%

Animal Models for Dysphagia Studies: What Have We Learnt So Far

et al. 2017

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Research using animal models has contributed significantly to realizing the goal of understanding dysfunction and improving the care of patients who suffer from dysphagia. But why should other researchers and the clinicians who see patients day in and day out care about this work? Results from studies of animal models have the potential to change and grow how we think about dysphagia research and practice in general, well beyond applying specific results to human studies. Animal research provides two key contributions to our understanding of dysphagia. The first is a more complete characterization of the physiology of both normal and pathological swallow than is possible in human subjects. The second is suggesting of specific, physiological, targets for development and testing of treatment interventions to improve dysphagia outcomes.

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“…We and others have reported bulbar deficits in SOD1-G93A transgenic mice and rats (11, 12, 13, 14). These studies validate these models as representing the full range of symptoms in ALS.…”

Section: Discussionmentioning

confidence: 63%

“…Until recently, preclinical studies with SOD1-G93A rodents have focused almost exclusively on spinal deficits. We and others have reported orolingual motor deficits in SOD1-G93A mice (11, 12, 13) and rats (14) that are analogous to bulbar deficits in ALS. A previous study reported heterogeneity with regard to spinal deficits that relates to survival in SOD1-G93A rats (10).…”

Section: Introductionmentioning

confidence: 66%

Relationships between tongue motility, grip force, and survival in SOD1-G93A rats

Smittkamp

Spalding

Brown

et al. 2014

Physiology & Behavior

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Most preclinical studies of amyotrophic lateral sclerosis (ALS) have focused on spinal symptoms, despite the importance of bulbar deficits in progression of the disease. We sought to determine how bulbar deficits related to spinal deficits and survival in the SOD1-G93A rat model of ALS. We examined forelimb and hindlimb grip force and tongue motility in SOD1-G93A rats using statistical cluster analysis. Decrements in forelimb grip force, hindlimb grip force, and tongue motility were used to cluster affected rats into groups. The analysis clustered one group that exhibited primarily forelimb deficits (forelimb group) and a second group that exhibited forelimb and tongue motility deficits (forelimb + bulbar group). The analysis did not identify a distinct hindlimb phenotype group because all SOD1-G93A rats exhibited deficits in hindlimb grip force. Rats in the forelimb + bulbar group exhibited earlier and greater forelimb deficits, and earlier mortality than rats without bulbar deficits. Hindlimb deficits were similar in both groups. There was a significant correlation between forelimb grip force and tongue motility deficits, but not between forelimb and hindlimb deficits. These data extend clinical findings of a more rapid disease progression in individuals with bulbar symptoms to the SOD1-G93A rat model of ALS.

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A Mouse Model of Pharyngeal Dysphagia in Amyotrophic Lateral Sclerosis

Cited by 37 publications

References 59 publications

Trends in Research Literature Describing Dysphagia in Motor Neuron Diseases (MND): A Scoping Review

Trends in Research Literature Describing Dysphagia in Motor Neuron Diseases (MND): A Scoping Review

Animal Models for Dysphagia Studies: What Have We Learnt So Far

Relationships between tongue motility, grip force, and survival in SOD1-G93A rats

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