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Upper motor neuron involvement in amyotrophic lateral sclerosis evaluated by triple stimulation technique and diffusion tensor MRI

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Abstract

The objective of this study was to evaluate the diagnostic value of triple stimulation technique (TST) and diffusion tensor imaging (DTI) tractography as markers of upper motor neuron (UMN) degeneration in amyotrophic lateral sclerosis (ALS). Fourteen ALS patients fulfilling the El Escorial criteria and 30 control subjects participated in the study. TST amplitude and area ratio were used as an estimate of the degree of central motor conduction failure. DTI fractional anisotropy was used as a quantitative measure of the structural integrity of the corticospinal tract and the posterior limb of the internal capsule. Mean TST amplitude and area ratio were lower in patients than controls, while there were no differences in mean fractional anisotropy of the corticospinal tract or the posterior limb of the internal capsule. TST was abnormal in 7/13 patients (sensitivity 54 %) and DTI was abnormal in 3/12 (sensitivity 25 %). Combining TST and DTI disclosed abnormalities in 8/11 patients (sensitivity 73 %). TST confirmed UMN degeneration in one of every 2.25 patient in the diagnostic categories lower than ‘probable’ ALS. Using results from TST as a criterion for UMN degeneration, four patients in diagnostic categories lower than ‘probable’ ALS and without clinical signs of UMN degeneration in the cervical region increased in diagnostic category. Our findings indicate that TST has a significant diagnostic value as an early objective marker of UMN degeneration in ALS, while the value of DTI analysis seems limited.

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Abbreviations

ADM:

Abductor digiti minimi muscle

AI:

Asymmetry index

ALS:

Amyotrophic lateral sclerosis

ALSFRS-R:

Revised amyotrophic lateral sclerosis functional rating scale

CMAP:

Compound muscle action potential

CMCT:

Central motor conduction time

CST:

Corticospinal tract

DTI:

Diffusion tensor imaging

DTR:

Deep tendon stretch reflex

EMG:

Electromyography

FA:

Fractional anisotropy

FACT:

Fiber assignment by continuous tracking

FEV(1):

Forced expiratory volume in the first second

FVC:

Forced vital capacity

ICBM:

International consortium for brain mapping

LMN:

Lower motor neuron

MD:

Mean diffusivity

MEP:

Motor evoked potential

MNI:

Montreal Neurological Institute

MR:

Magnetic resonance

MRC:

Medical research council

PLIC:

Posterior limb of internal capsule

ROI:

Region of interest

sd:

Standard deviation

TMS:

Transcranial magnetic stimulation

TST:

Triple stimulation technique

UMN:

Upper motor neuron

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Acknowledgments

This work was supported by the Lundbeck Foundation [R32-A2774]; the Danish Agency for Science, Technology and Innovation (founded by Danish Ministry of Science, Technology and Innovation) [271-06-0202] and Dagmar Marshalls Fond [5413455170]. These bodies had no role in the study design, implementation or manuscript preparation. The authors thank Per Christian Sidenius, MD and Bodil Holch Povlsen (Department of Neurology, Aarhus University) for their assistance with admission of patients, and research radiographers Dora Zeidler and Michael Geneser for their assistance with MRI recordings. We also thank following participants for patient inclusion: Carsten Bisgaard, MD (Neurology Department, Vejle Hospital); Mette-Kirstine Christensen, MD, PhD (Neurology Department, Aalborg Hospital, Aarhus University); Jens Arentsen, MD (Neurology Department, Holstebro Hospital). The authors thank all patients and control subjects who participated in the study.

Conflicts of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Clinical Neurophysiology, Aarhus University Hospital, Noerrebrogade 44, Building 10, Parterre, 8000, Aarhus C, Denmark

    Jasna Furtula, Birger Johnsen, Kirsten Pugdahl & Anders Fuglsang-Frederiksen

  2. Center of Functionally Integrative Neuroscience (CFIN), Aarhus University Hospital, Noerrebrogade 44, Building 10G, 5th floor, 8000, Aarhus C, Denmark

    Jesper Frandsen

  3. Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Noerrebrogade 44, Building 10G, 6th floor, 8000, Aarhus C, Denmark

    Anders Rodell

  4. Department of Neurology, Aarhus University Hospital, Noerrebrogade 44, Building 10, 3rd floor, 8000, Aarhus C, Denmark

    Peter Broegger Christensen

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  1. Jasna Furtula
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Correspondence to Jasna Furtula.

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Furtula, J., Johnsen, B., Frandsen, J. et al. Upper motor neuron involvement in amyotrophic lateral sclerosis evaluated by triple stimulation technique and diffusion tensor MRI. J Neurol 260, 1535–1544 (2013). https://doi.org/10.1007/s00415-012-6824-8

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  • DOI: https://doi.org/10.1007/s00415-012-6824-8

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