Does muscle reinnervation produce electromechanical dissociation in amyotrophic lateral sclerosis?

Venkatesh, Swamy; Shefner, Jeremy M.; Logigian, Eric L.

doi:10.1002/mus.880181119

Cited by 7 publications

(5 citation statements)

References 9 publications

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“…It remains to be seen whether preferential denervation and conversion cause changes in the muscle fibre proportions in ALS patients that account for dissociation between motor unit forces and increased size, as measured by EMG (Milner‐Brown et al 1974 a ; Venkatesh et al 1995; Vogt & Nix, 1997). Single muscle fibre data indicating no change in the specific force of muscle fibres from human patients indicate dissociation may result from the same mechanisms as we have suggested for the SOD1 G93A mice (Krivickas et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Preferential motor unit loss in the SOD1^G93A transgenic mouse model of amyotrophic lateral sclerosis

Hegedus

Putman

Tyreman

et al. 2008

The Journal of Physiology

217

193

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The present study investigated motor unit (MU) loss in a murine model of familial amyotrophic lateral sclerosis (ALS). The fast-twitch tibialis anterior (TA) and medial gastrocnemius (MG) muscles of transgenic SOD1G93A and SOD1 WT mice were studied during the presymptomatic phase of disease progression at 60 days of age. Whole muscle maximum isometric twitch and tetanic forces were 80% lower (P < 0.01) in the TA muscles of SOD1 G93A compared to SOD1 WT mice. Enumeration of total MU numbers within TA muscles showed a 60% reduction (P < 0.01) within SOD1 G93A mice (38 ± 7) compared with SOD1 WT controls (95 ± 12); this was attributed to a lower proportion of the most forceful fast-fatigable (FF) MU in SOD1 G93A mice, as seen by a significant (P < 0.01) leftward shift in the cumulative frequency histogram of single MU forces. Similar patterns of MU loss and corresponding decreases in isometric twitch force were observed in the MG. Immunocytochemical analyses of the entire cross-sectional area (CSA) of serial sections of TA muscles stained with anti-neural cell adhesion molecule (NCAM) and various monoclonal antibodies for myosin heavy chain (MHC) isoforms showed respective 65% (P < 0.01) and 28% (P < 0.05) decreases in the number of innervated IIB and IID/X muscle fibres in SOD1 G93A , which paralleled the 60% decrease (P < 0.01) in the force generating capacity of individual fibres. The loss of fast MUs was partially compensated by activity-dependent fast-to-slower fibre type transitions, as determined by increases (P < 0.04) in the CSA and proportion of IIA fibres (from 4% to 14%) and IID/X fibres (from 31% to 39%), and decreases (P < 0.001) in the CSA and proportion of type IIB fibres (from 65% to 44%). We conclude that preferential loss of IIB fibres is incomplete at 60 days of age, and is consistent with a selective albeit gradual loss of FF MUs that is not fully compensated by sprouting of the remaining motoneurons that innervate type IIA or IID/X muscle fibres. Our findings indicate that disease progression in fast-twitch muscles of SOD1 G93A

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Section: Discussionmentioning

confidence: 99%

Preferential motor unit loss in the SOD1^G93A transgenic mouse model of amyotrophic lateral sclerosis

Hegedus

Putman

Tyreman

et al. 2008

The Journal of Physiology

217

193

View full text Add to dashboard Cite

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“…5) It provides a means to follow quantitatively the natural history of myotonia in patients with DM1, to determine the efficacy of antimyotonia treatment such as mexiletine, and to assess geneticphysiologic correlations. We are aware that the twitch technique described here, and also used in our previous studies, 8,9 reflects the force output of several ulnar-innervated muscles. Contraction of the adductor pollicis likely adds to the recorded twitch tension, whereas that of the first palmar interosseous subtracts from it.…”

Section: Twitch (Left) and Tetanic (Right) Relaxation Times (Rt) Onmentioning

confidence: 96%

“…This limitation stems in part from a lack of reproducible, quantitative methods to measure myotonia. The goals of this study are to 1) assess the feasibility and reliability of using force recordings of twitch and tetanic contractions of the first dorsal interosseous muscle (FDI) following ulnar stimulation at the wrist 8,9 to measure the delay of muscle relaxation (myotonia) in patients with DM1 and 2) investigate the relationship of myotonia to CTG repeat length in DM1.…”

mentioning

confidence: 99%

Leukocyte CTG repeat length correlates with severity of myotonia in myotonic dystrophy type 1

et al. 2004

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“…MUs were functionally characterized by the size of the macro-MUPs obtained in intramuscular recordings, 55 the amplitude of the twitch force, 17,54 and the ratio of these two parameters (i.e., contractile effectiveness). 54,61 The functional state of the motoneuron itself was evaluated on the basis of the duration and variability of interspike intervals (ISI). 40 For comparison, similar investigations were performed on patients with Kennedy's disease.…”

Section: Accepted 21 December 2005mentioning

confidence: 99%

Cortical versus spinal dysfunction in amyotrophic lateral sclerosis

et al. 2006

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Little is known about the possible link between cortical and spinal motor neuron dysfunction in amyotrophic lateral sclerosis (ALS). We correlated the characteristics of the responses to transcranial magnetic stimulation (TMS) with the electromechanical properties and firing pattern of single motor units (MUs) tested in nine ALS patients, three patients with Kennedy's disease, and 15 healthy subjects. In Kennedy's disease, 19 of 22 MUs were markedly enlarged with good electromechanical coupling and discharged with great variability. Their excitatory responses increased with MU size. In ALS, 17 of 34 MUs with excitatory responses behaved as in Kennedy's disease. By contrast, 28 MUs with nonsignificant responses showed poor electromechanical coupling and high firing rates, whereas 28 MUs with inhibitory responses showed moderate functional alterations. This result indicates that in ALS as in Kennedy's disease, sprouting of corticospinal axons may occur on surviving motoneurons. A clear relationship exists between the responsiveness of MUs to TMS and their functional state.

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Does muscle reinnervation produce electromechanical dissociation in amyotrophic lateral sclerosis?

Cited by 7 publications

References 9 publications

Preferential motor unit loss in the SOD1^G93A transgenic mouse model of amyotrophic lateral sclerosis

Preferential motor unit loss in the SOD1^G93A transgenic mouse model of amyotrophic lateral sclerosis

Leukocyte CTG repeat length correlates with severity of myotonia in myotonic dystrophy type 1

Cortical versus spinal dysfunction in amyotrophic lateral sclerosis

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Does muscle reinnervation produce electromechanical dissociation in amyotrophic lateral sclerosis?

Cited by 7 publications

References 9 publications

Preferential motor unit loss in the SOD1G93A transgenic mouse model of amyotrophic lateral sclerosis

Preferential motor unit loss in the SOD1G93A transgenic mouse model of amyotrophic lateral sclerosis

Leukocyte CTG repeat length correlates with severity of myotonia in myotonic dystrophy type 1

Cortical versus spinal dysfunction in amyotrophic lateral sclerosis

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Product

Resources

About

Preferential motor unit loss in the SOD1^G93A transgenic mouse model of amyotrophic lateral sclerosis

Preferential motor unit loss in the SOD1^G93A transgenic mouse model of amyotrophic lateral sclerosis