Date of download: 5/28/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Increased Metabolic Muscle Fatigue Is Caused by Some but Not All Mitochondrial Mutations Arch Neurol. 2003;60(1): doi: /archneur The stabilizing device used to measure the torque generated by ankle dorsiflexor muscles. Once supramaximal stimulation was identified (as also noted by maximal compound muscle action potential amplitudes), the foot plate was rotated until optimal muscle length (ie, for maximal twitch force at a given stimulus) was identified. Subsequently, all fatigue rate data were obtained with these parameters maintained. The entire stabilizing device and all attachments are made from aluminum plates (6 mm thick). Weight leg stabilization: total = 9.07 kg; in-line skate boot = 0.90 kg. Figure Legend:

Date of download: 5/28/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Increased Metabolic Muscle Fatigue Is Caused by Some but Not All Mitochondrial Mutations Arch Neurol. 2003;60(1): doi: /archneur Muscle torque recordings of a healthy man. Top half, A, Muscle torque of the left ankle dorsiflexors. This record indicates the standard stimulation protocol employed for each individual. Supramaximal electrical stimuli were given to the common peroneal nerve at rates shown above the waveforms. B, Expanded view of part A, at the beginning of the stimulation rate of 2 per second. The amplitude of each muscle twitch was determined automatically, and pluses indicate points that were automatically set for the amplitude measurements. C, Expanded view of part A, at the beginning of the stimulation rate of 5 per second. Note that the torque does not return to the baseline after each stimulus, indicating a partially tetanic muscle contraction. Lower half, Amplitudes of the twitches of the waveforms shown. Figure Legend:

Date of download: 5/28/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Increased Metabolic Muscle Fatigue Is Caused by Some but Not All Mitochondrial Mutations Arch Neurol. 2003;60(1): doi: /archneur Muscle torque recordings of a patient with chronic progressive external ophthalmoplegia. Upper half, A, Muscle torque of the left ankle dorsiflexors. Supramaximal electrical stimuli were given to the common peroneal nerve at rates shown above the waveforms (patient 2 [further data provided in Table 1]). B, Expanded view of part of A, at the beginning of the stimulation rate of 2 per second; the amplitude of each muscle twitch was determined automatically. Pluses indicate points that were automatically set for the amplitude measurements. C, Expanded view of part A, at the beginning of the stimulation rate of 5 per second. Lower half, Amplitudes of the twitches of the waveforms shown in the top half. Figure Legend:

Date of download: 5/28/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Increased Metabolic Muscle Fatigue Is Caused by Some but Not All Mitochondrial Mutations Arch Neurol. 2003;60(1): doi: /archneur Definition of twitch fatigue. Twitch amplitude and compound muscle action potential amplitude (CMAP) of 120 twitches of the left ankle dorsiflexors recorded from a healthy control subject (patient 2). Twitches were evoked by a train of supramaximal electrical stimuli given to the common peroneal nerve at a rate of 2 per second. TA 0 indicates twitch amplitude of the first muscle twitch of the stimulus train. TA 50 indicates mean of the twitch amplitude values of all twitches recorded after the 50th second of the stimulus train (horizontal bar). Definition of twitch fatigue is explained by the formula (TA 0 − TA 50 )/TA 0. Figure Legend:

Date of download: 5/28/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Increased Metabolic Muscle Fatigue Is Caused by Some but Not All Mitochondrial Mutations Arch Neurol. 2003;60(1): doi: /archneur Amplitude of muscle twitches following supramaximal electrical stimuli. Trains (60-second duration) of stimuli were given at a rate indicated at the abscissa (further data shown in Figure 2). The value shown is the amplitude of the first twitch response of each train (see TA 0 in Figure 4). A and D, Healthy controls. B and E, Patients with mitochondrial disorders. C and F, Patients with other neuromuscular disorders. Thick lines indicate lower 95% limits of normal; CPEO, chronic progressive external ophthalmoplegia. Figure Legend:

Date of download: 5/28/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Increased Metabolic Muscle Fatigue Is Caused by Some but Not All Mitochondrial Mutations Arch Neurol. 2003;60(1): doi: /archneur Muscular twitch fatigue at different rates of stimulation. A and D, Healthy controls. B and E, Patients with mitochondrial disorders. C, Patients with other neuromuscular disorders. Thick lines indicate upper 95% limits of normal. CPEO indicates chronic progressive external ophthalmoplegia. Figure Legend:

Date of download: 5/28/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Increased Metabolic Muscle Fatigue Is Caused by Some but Not All Mitochondrial Mutations Arch Neurol. 2003;60(1): doi: /archneur Twitch fatigue and muscle force. A, Muscular twitch fatigue vs twitch amplitude of the ankle dorsiflexor muscles on the first stimulus of a 60-second series (stimulus rate, 2 per second). Further data are provided in Table 1. Fatigue increased in a nonlinear way with decreasing muscle force. Solid line and formula are the result of nonlinear regression of twitch fatigue of patients with other neuromuscular disorders (ONMD) and controls to twitch amplitude (r = 0.67; P<.001). B, Results of the regression equation subtracted from fatigue values. Horizontal lines indicate standard deviation of the values of patients with ONMD and controls. Specific fatigue values of patients with mitochondrial encephalomyopathies (those with chronic progressive external ophthalmoplegia [CPEO] and mutations) are significantly higher than those of patients with ONMD and controls (t test: P<.001). Fatigue = 1/( *[twitch amplitude/per Newtonmeter]). Figure Legend: