A multicenter, randomized, double-blinded trial of pyridostigmine in postpolio syndrome.

BACKGROUND: Postpoliomyelitis syndrome (PPS) is likely due to degeneration and dysfunction of terminal axons of enlarged postpolio motor units. Age-related decline in growth hormone and insulin-like growth factor (IGF-I) may be a contributing factor. Neuromuscular junction abnormalities and decreased IGF-I levels may respond to the anticholinesterase pyridostigmine, with consequent improvement in strength, fatigue, and quality of life. OBJECTIVES: To determine the effect of pyridostigmine in PPS on health-related quality of life, isometric muscle strength, fatigue, and serum IGF-I levels; and to assess the safety of pyridostigmine in PPS. METHODS: The study was a multicenter, randomized, double-blinded, placebo-controlled trial of a 6-month course of pyridostigmine 60 mg three times per day in 126 PPS patients. The primary data analysis compared mean changes of outcomes between treatment and control groups at 6 months using an intention to treat approach. Secondary analyses included a comparison of outcomes at 6 and 10 weeks, and in compliant patients. RESULTS: The study showed no significant differences in pyridostigmine and placebo-treated patients with regard to changes in quality of life, isometric strength, fatigue, and IGF-I serum levels at 6 months in the primary analysis and in compliant patients. There were no differences in outcomes at 6 and 10 weeks between groups. However, very weak muscles (1 to 25% predicted normal at baseline) were somewhat stronger (p = 0.10, 95% CI of difference -9.5 to 73.3%), and in compliant patients IGF-I was somewhat increased (p = 0.15, 95% CI of difference -6.4 to 44.8 ng/mL) at 6 months with the medication. Pyridostigmine was generally well tolerated. CONCLUSIONS: This study showed no significant differences between pyridostigmine and placebo-treated PPS patients on measures of quality of life, isometric strength, fatigue, and serum IGF-I.

The role of exercise in the patient with post-polio syndrome.

Recent studies have shown that judicious exercise can improve muscle strength, cardiorespiratory fitness, and the efficiency of ambulation in post-polio patients. It may also add to the patient's sense of well-being. These benefits appear to occur when the patients stay within reasonable bounds while exercising in order to avoid overuse problems. In particular, the patients should be instructed to avoid activities that cause increasing muscle or joint pain or excessive fatigue, either during or after their exercise program. The literature indicates that exercise within these constraints leads to a number of beneficial physiologic and psychologic adaptations in patients with post-polio syndrome. Judicious exercise should be viewed as important adjuvant in the overall therapeutic program of the patient. Patients seen in post-polio clinics frequently complain of new fatigue, weakness, muscle pain, and/or joint pain. The most frequent complaints involving activities of daily living include new difficulties with walking and stair climbing. The therapeutic benefit of exercise in these patients to minimize or reverse decline in function is an important question frequently asked by patients with post-polio syndrome. In the general population, physical activity is known to be an important adjunct to good health, bestowing both physiologic and psychologic benefits leading to a reduction in the risk to develop a number of serious ailments as well as leading to better psychological adjustment. On the other hand, limitation in physical activity results in a number of deleterious effects. Patients with post-polio syndrome have unique problems, however, which need to be considered when prescribing an exercise program for an individual patient. A number of functional etiologies for declining function have been hypothesized including disuse weakness, overuse weakness, weight gain, and chronic weakness. Because of the variability in which the motor neurons to different muscle groups may have been affected in a particular patient, both asymmetric and scattered weakness may be present. The challenge in prescribing exercise for the patient with post-polio syndrome comes in recognizing these unique factors in each patient and modifying the prescription accordingly. One must protect muscles and joints experiencing the adverse effects of overuse or body areas with very significant chronic weakness (in general, in areas where the muscles have less than antigravity strength on manual muscle testing) while exercising those body areas experiencing the deleterious effects of disuse. Weight gain is to be avoided if at all possible in this population, because increased weight only leads to further difficulty in the performance of daily activities.(ABSTRACT TRUNCATED AT 400 WORDS)

Rate of decline in blood lactate after cycling exercise in endurance-trained and -untrained subjects.

The purpose of this study was to compare the rate of decline in blood lactate (La) levels in nine trained men [maximal O2 consumption (VO2max) 65.5 +/- 3.3 ml.kg-1.min-1] and eight untrained men (VO2max 42.2 +/- 2.8 ml.kg-1.min-1) during passive recovery from a 3-min exercise bout. Trained and untrained subjects cycled at 85 and 80% VO2max, respectively, to produce similar peak blood La concentrations. Twenty samples of arterialized venous blood were drawn from a heated hand vein during 60 min of recovery and analyzed in an automated La analyzer. The data were then fitted to a biexponential function, which closely described the observed data (r = 0.97-0.98). There was no difference in the coefficient expressing the rate of decline in blood La for trained and untrained groups (0.0587 +/- 0.0111 vs. 0.0579 +/- 0.0100, respectively). However, trained subjects demonstrated a faster time-to-peak La (P = 0.01), indicative of a faster efflux of La from muscle to blood. Thus the rate of decline in blood La after exercise does not appear to be affected by training. The faster decline previously reported for trained subjects may be due to the use of a linear rather than a biexponential curve fit.

Influence of muscle length and force on endurance and pressor responses to isometric exercise.

Experiments were performed to determine whether endurance time, mean arterial pressure, or heart rate was related to either muscle length or external torque production in humans during isometric knee extension. Eight men and nine women performed isometric knee extension to the endurance limit at each of three muscle lengths, determined by knee angles of 40 degrees (0.698 rad, shortest), 60 degrees (1.047 rad, intermediate), and 90 degrees (1.571 rad, longest), and at intensities of 30 and 50% maximal voluntary contraction (MVC). Knee extension forms an ascending-descending length-torque curve, and lengths were chosen to result in different external torques. MVC was greatest at a knee angle of 60 degrees (P < 0.05 vs. 40 degrees, 90 degrees), with no significant difference between 90 degrees and 40 degrees. Endurance time was inversely related to muscle length, independent of torque production, at 30% MVC [40 degrees, 395 +/- 139 (SE); 60 degrees, 237 +/- 60; 90 degrees, 165 +/- 51 s; P < 0.05 vs. each other] and 50% MVC (40 degrees, 176 +/- 64; 60 degrees, 137 +/- 40; 90 degrees, 85 +/- 23 s; P < 0.05 vs. each other). Evidence is presented that endurance is a function of internal muscle force and not resultant external torque. The experimental design allowed the relationship of external torque and cardiovascular responses to be examined independent of exercise intensity. Muscle mass was also controlled in that the same muscle group was involved in all contractions. There were no differences in mean arterial pressure, heart rate, or rating of perceived exertion at any percentage of endurance time under any condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum insulin-like growth factor-I (IGF-I) does not correlate positively with isometric strength, fatigue, and quality of life in post-polio syndrome.

OBJECTIVES AND BACKGROUND: To determine if serum insulin-like growth factor-I (IGF-I) levels are associated with strength, body mass index (BMI), fatigue, or quality of life in post-poliomyelitis syndrome (PPS). PPS is likely due to a distal disintegration of enlarged post-polio motor units as a result of terminal axonal sprouting. Age-related decline in growth hormone and IGF-I (which support terminal axonal sprouts) is proposed as a contributing factor. METHODS: As part of the North American Post-Poliomyelitis Pyridostigmine Study (NAPPS), baseline data on maximum voluntary isometric contraction (MVIC), BMI, subjective fatigue (fatigue severity scale, Hare fatigue symptom scale), health-related quality of life (short form health survey-36; SF-36), and serum IGF-I levels were gathered on 112 PPS patients. Pearson correlation coefficients were calculated to evaluate the association between serum IGF-I and MVIC in 12 muscles, BMI, two fatigue scales, and SF-36 scale scores. RESULTS: There is a significant inverse correlation of IGF-I levels with MVIC in left ankle dorsiflexors (r=-0.30, P<0.01), and left and right knee extensors (r=-0.22, -0.25, P=<0.01, 0.01), but no significant correlations in other muscles. When men and women were evaluated separately, inverse correlations of IGF-I levels with MVIC were found only in men. IGF-I correlated inversely with BMI (r=-0.32, P=0006) and age (r=-0.32, P=0.0005). IGF-I did not correlate with the fatigue or SF-36 scales. CONCLUSIONS: In this exploratory study, we found that contrary to our expectations, IGF-I did not correlate positively with strength. IGF-I correlated negatively with strength in several lower extremity muscles, BMI, and age. IGF-I is likely not an important factor in the pathogenesis of fatigue and in determining quality of life in PPS, but its role on strength should be studied further.

Hamstring injuries. Proposed aetiological factors, prevention, and treatment.

Injuries to the hamstring muscles can be devastating to the athlete because these injuries frequently heal slowly and have a tendency to recur. It is thought that many of the recurrent injuries to the hamstring musculotendinous unit are the result of inadequate rehabilitation following the initial injury. The severity of hamstring injuries is usually of first or second degree, but occasionally third-degree injuries (complete rupture of the musculotendinous unit) do occur. Most hamstring strain injuries occur while running or sprinting. Several aetiological factors have been proposed as being related to injury of the hamstring musculotendinous unit. They include: poor flexibility, inadequate muscle strength and/or endurance, dyssynergic muscle contraction during running, insufficient warm-up and stretching prior to exercise, awkward running style, and a return to activity before complete rehabilitation following injury. Treatment for hamstring injuries includes rest and immobilisation immediately following injury and then a gradually increasing programme of mobilisation, strengthening, and activity. Permission to return to athletic competition should be withheld until full rehabilitation has been achieved (complete return of muscle strength, endurance, and flexibility in addition to a return of co-ordination and athletic agility). Failure to achieve full rehabilitation will only predispose the athlete to recurrent injury. The best treatment for hamstring injuries is prevention, which should include training to maintain and/or improve strength, flexibility, endurance, co-ordination, and agility.

Compatibility of adaptive responses with combining strength and endurance training.

Impairment in strength development has been demonstrated with combined strength and endurance training as compared with strength training alone. The purpose of this study was to examine the effects of combining conventional 3 d.wk-1 strength and endurance training on the compatibility of improving both VO2peak and strength performance simultaneously. Sedentary adult males, randomly assigned to one of three groups (N = 10 each), completed 10 wk of training. A strength-only (S) group performed eight weight-training exercises (4 sets/exercise, 5-7 repetitions/set), an endurance-only (E) group performed continuous cycle exercise (50 min at 70% heart rate reserve), and a combined (C) group performed the same S and E exercise in a single session. S and C groups demonstrated similar increases (P < 0.0167) in 1RM squat (23% and 22%) and bench press (18% for both groups), in maximal isometric knee extension torque (12% and 7%), in maximal vertical jump (6% and 9%), and in fat-free mass (3% and 5%). E training did not induce changes in any of these variables. VO2peak (ml.kg-1.min-1) increased (P < 0.01) similarly in both E (18%) and C (16%) groups. Results indicate 3 d.wk-1 combined training can induce substantial concurrent and compatible increases in VO2peak and strength performance.

Effect of training on VO2max, thigh strength, and muscle morphology in septuagenarian women.

The purpose of this study was to determine the effects of a long-term (50 wk) combined aerobic-resistance training program on maximal oxygen consumption (VO2max, thigh strength, and vastus lateralis fiber morphology in healthy septuagenarian women (mean age = 72 +/- 6 yr). Subjects volunteered to be in either an exercise (Ex; N = 17) or control (Con; N = 10) group. Con subjects were 34% less active in winter than in summer, Ex subjects maintained their summer activity level on exercise days in winter. Initial, intermediate (20 wk), and final (50 wk) measurements were made for isokinetic knee extension/flexion strength; VO2max and morphological measurements from a muscle biopsy were made at the initial and final times only. Both groups gained in leg strength (Ex = +6.5%; Con = +7.8%; P less than or equal to 0.05) during the summer; in the winter the Ex group maintained leg strength and the Con group declined 12.2% (P less than or equal to 0.05). The fast-twitch muscle fiber area (Type IIb) increased 29% (P less than or equal to 0.001) in the Ex group and declined 26% (P = 0.014) in the Con group. VO2max increased only in the Ex group (16%; P less than 0.001). We conclude that healthy septuagenarian women can increase aerobic capacity, leg strength, and Type IIb muscle fiber area with a long-duration, combined aerobic-resistance exercise program.

Muscular function in late polio and the role of exercise in post-polio patients.

Many post-polio individuals note new musculoskeletal and neuromuscular symptoms. In general, post-polio individuals are found to be weaker than non-postpolio individuals. Muscle weakness appears to play a role in functional limitations in post-polio individuals, especially for such activities as walking and stair climbing. Many post-polio individuals also have deficits in muscular work capacity and strength recovery following activity. Importantly, post-polio individuals are known to have normal perception of local muscle fatigue during activity. The perception of fatigue within the working muscle can be used to modify activity and to assist the individual in the avoidance of excessive local fatigue during exercise and performance of activities of daily living. Recent studies have shown that judicious exercise can improve muscle strength, range of motion, cardiorespiratory fitness, efficiency of ambulation as well as add to the patient's sense of well-being. These benefits appear to occur when activity and exercise are kept within reasonable limits in order to avoid excessive muscular fatigue and/or joint or muscle pain. It is suggested that post-polio patients be instructed to avoid activities that cause increasing muscle or joint pain or excessive fatigue, either during or after their exercise program as the performance of activity at too high a level may lead to overuse/overwork problems. The recent literature indicates that exercise within the constraints of fatigue and pain leads to a number of beneficial physiologic adaptations. Judicious exercise should be viewed as an adjuvant in the overall therapeutic program of the post-polio patient, when the individual has the physiologic capacity to exercise.

Isokinetic strength testing in older women: a comparison of two systems.

FUNDING: National Institute of Aging; University of Wisconsin Graduate School. Isokinetic equipment is used for measuring muscular strength for both experimental and rehabilitative purposes. In this study two LIDO(R) isokinetic dynamometer systems, the LIDO-digital and the LIDO-active, were compared at 60, 180, 240, and 300 degrees /see for peak torque (PT) and average work output (WO) of knee flexion and extension. Twenty-five elderly women (age range = 65-86) were tested on both systems within seven days. The data were compared by using a repeated measures ANOVA followed by a Dunn-Bonferroni posthoc comparison (p

Neuromuscular function in polio survivors.

Although there is no documented, objective evidence that symptomatic post-polio subjects are rapidly losing strength, they have a number of neuromuscular deficits related to a more severe poliomyelitis illness that may explain why they complain of problems with strength, endurance, and local muscle fatigue. Symptomatic post-polio subjects were hospitalized longer during the acute poliomyelitis, recovered more slowly, and had electromyographic evidence of greater loss of anterior horn cells. Additionally, recent assessment demonstrated that they were weaker, had a reduced work capacity, and recovered strength less readily after activity in the quadriceps muscles as compared to asymptomatic subjects. Of great clinical importance, rating of perceived exertion in the muscle during exercise was the same in symptomatic and asymptomatic post-polio and control subjects, indicating that symptomatic subjects have a mechanism to monitor local muscle fatigue that could be used to avoid exhaustion. A study of pacing (interspersing activity with rest breaks) showed that symptomatic subjects had less local muscle fatigue and greater strength recovery when they paced their activity than when they worked at a constant rate to exhaustion. We recommend that post-polio individuals pace their daily activity to avoid excessive fatigue.

Intermittent isometric activity: its effect on muscle fatigue in postpolio subjects.

Symptomatic postpolio patients report improved function when they pace their activities, but this has never been objectively assessed. The purpose of this study was to determine whether seven symptomatic postpolio subjects would (1) have less evidence of local muscle fatigue and recover strength more readily when they pace their activity (via work-rest intervals) than when they work at a constant rate to exhaustion, and (2) be able to perform more work with less fatigue by pacing. Subjects were evaluated on three separate days with at least one week between tests. On the first test day (constant exercise), isometric peak torque (MVC) of the quadriceps was determined and an isometric endurance test was performed to exhaustion at 40% of MVC. Thirty seconds after exhaustion the subject performed an MVC. One psychophysiologic and two electrophysiologic variables associated with fatigue were measured during the testing procedure. Work capacity (TTI) was determined as torque x time. In test 2 (quartile exercise), the same TTI was performed at 40% of MVC, but in this instance the work was performed in quartiles with two-minute rest breaks between work quartiles rather than continuously to exhaustion. In test 3 (interval exercise), exercise was performed at 40% of MVC in 20-second bouts with two-minute rest breaks until rating of perceived exertion exceeded 17 (very hard), or until six-minutes of work were performed. Analyses demonstrated that both work-rest interval programs resulted in less evidence of local muscle fatigue, increased capacity to perform work, and increased ability to recover strength after activity in symptomatic postpolio patients.

Electrophysiologic study of the quadriceps muscles during fatiguing exercise and recovery: a comparison of symptomatic and asymptomatic postpolio patients and controls.

This study was performed to determine whether deficits in muscle strength, work capacity, and ability to recover strength after exhaustion in symptomatic postpolio subjects were due to central inhibition (lassitude) or other physiologic differences. We studied 34 symptomatic polio subjects, 16 asymptomatic polio subjects, and 41 control subjects. Root mean squared electromyography (RMS-EMG) and the median frequency (Fm) of the power spectrum of the quadriceps muscle was determined with surface electrodes during maximal volitional contraction (MVC) of isometric knee extension, an endurance test to exhaustion at 40% of maximal torque, and strength recovery testing that was performed at regular intervals for 10 minutes postexhaustion. Initial Fm during MVC and during the 40% MVC endurance test were similar in all three groups. The Fm decreased during the endurance test and increased during recovery similarly in all three groups. The RMS-EMG also changed in parallel fashion in all three groups during the same procedures. During recovery, a similar degree of RMS-EMG facilitation was seen in all three groups. Thus, reduction in strength, work capacity, and ability to recover from fatiguing exercise do not appear to be related to central factors (lassitude); they are probably related to other factors, such as local muscle fatigue. Each group appears to fatigue and recover in a similar manner electrophysiologically, although symptomatic polio subjects have a deficit in strength recovery, apparently due to local muscular fatigue.

Neuromuscular function in polio survivors at one-year follow-up.

Many polio survivors complain of progressive loss of strength, work capacity, endurance, and ability to recover from fatiguing activity. These variables were measured initially and one year later in the quadriceps muscles of 28 symptomatic and 16 asymptomatic persons who had polio and 38 control individuals. Peak knee extension torque was measured isokinetically and isometrically. Endurance, or the amount of time the subject could maintain isometric torque at 40% of maximal torque, was measured. Work capacity was determined as the product of isometric torque and endurance time. Recovery of strength was measured at regular intervals for ten minutes after the endurance test. Statistical analysis was done by repeated measures ANOVA. Although the initial measures showed significant deficits in mean peak torque, work capacity, and recovery of strength in symptomatic postpolio subjects, no significant changes were found one year later in any of the variables. We conclude that symptomatic postpolio subjects do not lose significant neuromuscular function in one year.

Physiologic parameters and perceived exertion with local muscle fatigue in postpolio subjects.

Fifty postpolio patients, 34 with and 16 without complaints of progressive loss of muscle strength, and 41 control subjects were studied to compare physiologic measures of the fatiguing process and to determine whether there is a significant interaction between the rating of perceived exertion (RPE) and physiologic measures. Statistical analyses were by ANOVA and repeated-measures ANOVA. The RPE was obtained every 20 seconds during an isometric contraction of the quadriceps at 40% of maximal torque; median frequency (Fm) of the power spectrum of the surface electromyographic signal and neuromuscular efficiency (NME) were constantly monitored. The RPE increased similarly (p greater than .05), whereas Fm and NME decreased similarly (p greater than .05) during endurance exercise at 40% of maximal torque in all three groups. A significant (p less than .05) interaction was found between RPE and both Fm and NME. We conclude that physiologic measures of the fatiguing process (Fm and NME) occur in a similar manner in postpolio and control subjects and that there is a significant interaction between subjective RPE and physiologic measures of the fatiguing process.

Correlation of motor units with strength and spectral characteristics in polio survivors and controls.

The purpose of this study was to determine whether quantitative motor unit analysis in postpolio individuals correlates with muscle strength, endurance, work capacity, or power spectral characteristics of surface EMG and to determine whether power spectrum differentiates postpolio from control subjects. This study was designed to compare these variables in 34 symptomatic postpolio, 16 asymptomatic postpolio, and 41 control subjects. Quantitative motor unit analysis of the quadriceps femoris muscle was performed using a concentric needle electrode. Isometric knee extension peak torque, endurance (time to exhaustion) at 40% of maximal torque, work capacity (tension time index), and recovery of force through 10 minutes post-exhaustion were determined. Median frequency of the surface power spectrum was determined during the above testing. Power spectrum histograms were compared at the onset and termination of endurance exercise. Motor unit action potential variables did not correlate with isometric peak torque, tension time index, endurance time, recovery of strength, or with median frequency. Surface power spectrum did not differentiate postpolio from control subjects.