More recently, biallelic COL13A1 loss-of-function mutations were identified in three patients with congenital myasthenic syndrome (CMS), a rare inherited condition with defective neuromuscular transmission, causing abnormal fatigability and fluctuating muscle weakness and often successfully treated with acetylcholinesterase inhibitors.
We hypothesise that pyridostigmine, an acetylcholinesterase inhibitor that improves neuromuscular transmission, could improve NMJ function and thereby muscle strength and fatigability in patients with SMA.
At both ages, the diaphragm's amplitude of contraction and fatigability index were higher in the CPF-5 group, due to lower acetylcholinesterase activity.
Studies of muscle contractile properties showed muscle fatigability at low frequencies of nerve stimulation and suggested that partial endplate AChE deficiency might contribute to SJS muscle stiffness by potentiating muscle force.
We studied 4 siblings (3 men and 1 woman), ages 22 to 43 years, with congenital ptosis, external ophthalmoplegia, proximal muscle weakness and fatigability unresponsive to acetylcholinesterase (AChE) inhibitors.
Cross-sectional associations between ASTP and gait speed (m/s), fatigability (rating-of-perceived-exertion [RPE]), 400 m time (seconds), and expanded short physical performance battery score were modeled using linear and logistic regression, adjusted for chronic conditions.
We demonstrate that chronically elevated interleukin-6 increased skeletal muscle fatigability and disrupted mitochondrial content and function independent of changes in fibre type and mass.
Postnatal activin/myostatin type IIB receptor (ActRIIB) blockade increases skeletal muscle mass and strength but also increases muscle fatigability and impairs oxidative metabolism.
SOD1-G93R zebrafish showed decreased embryonic nerve length with increased BMAA dose, a phenotypic change mirrored in 5-month performance measures of weaker swimming and increased fatigability.
More recently, biallelic COL13A1 loss-of-function mutations were identified in three patients with congenital myasthenic syndrome (CMS), a rare inherited condition with defective neuromuscular transmission, causing abnormal fatigability and fluctuating muscle weakness and often successfully treated with acetylcholinesterase inhibitors.
SUR2 loss-of-function causes fatigability and cardiac dysfunction in mice, and reduced activity, cardiac dysfunction and ventricular enlargement in zebrafish.
Despite increased muscle mass for HFD soleus and EDL, absolute isometric force, isometric stress (force/CSA), PO normalised to muscle mass and fatigability was unchanged, although absolute PO was significantly greater.
In categorical analyses, those in the highest tertile of ASTP were >2 times more likely to have high fatigability (rating of perceived exertion ≥10), slow 400 m time (>300 seconds) and reduced functional performance (expanded short physical performance battery score < 3.07) than those in the lowest tertile (p < .01).
Despite increased muscle mass for HFD soleus and EDL, absolute isometric force, isometric stress (force/CSA), PO normalised to muscle mass and fatigability was unchanged, although absolute PO was significantly greater.
Despite increased muscle mass for HFD soleus and EDL, absolute isometric force, isometric stress (force/CSA), PO normalised to muscle mass and fatigability was unchanged, although absolute PO was significantly greater.
Despite increased muscle mass for HFD soleus and EDL, absolute isometric force, isometric stress (force/CSA), PO normalised to muscle mass and fatigability was unchanged, although absolute PO was significantly greater.
SUR2 loss-of-function causes fatigability and cardiac dysfunction in mice, and reduced activity, cardiac dysfunction and ventricular enlargement in zebrafish.