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Journal of Neurology

, Volume 264, Issue 5, pp 882–890 | Cite as

Peripheral nerve diffusion tensor imaging as a measure of disease progression in ALS

  • Neil G. Simon
  • Jim Lagopoulos
  • Sita Paling
  • Casey Pfluger
  • Susanna B. Park
  • James Howells
  • Thomas Gallagher
  • Michel Kliot
  • Robert D. Henderson
  • Steve Vucic
  • Matthew C. Kiernan
Original Communication

Abstract

Clinical trial design in amyotrophic lateral sclerosis (ALS) remains hampered by a lack of reliable and sensitive biomarkers of disease progression. The present study evaluated peripheral nerve diffusion tensor imaging (DTI) as a surrogate marker of axonal degeneration in ALS. Longitudinal studies were undertaken in 21 ALS patients studied at 0 and 3 months, and 19 patients at 0, 3 and 6 months, with results compared to 13 age-matched controls. Imaging metrics were correlated across a range of functional assessments including amyotrophic lateral sclerosis functional rating scale revised (ALSFRS-R), lower limb muscle strength (Medical Research Council sum score, MRCSS-LL), compound muscle action potential amplitudes and motor unit number estimation (MUNE). Fractional anisotropy was reduced at baseline in ALS patients in the tibial (p < 0.05), and peroneal nerve (p < 0.05). Fractional anisotropy and axial diffusivity declined in the tibial nerve between baselines, 3- and 6-month scans (p < 0.01). From a functional perspective, ALSFRS-R correlated with fractional anisotropy values from tibial (R = 0.75, p < 0.001) and peroneal nerves (R = 0.52, p = 0.001). Similarly, peroneal nerve MUNE values correlated with fractional anisotropy values from the tibial (R = 0.48, p = 0.002) and peroneal nerve (R = 0.39, p = 0.01). There were correlations between the change in ALSFRS-R and tibial nerve axial diffusivity (R = 0.38, p = 0.02) and the change in MRCSS-LL and peroneal nerve fractional anisotropy (R = 0.44, p = 0.009). In conclusion, this study has demonstrated that some peripheral nerve DTI metrics are sensitive to axonal degeneration in ALS. Further, that DTI metrics correlated with measures of functional disability, strength and neurophysiological measures of lower motor neuron loss.

Keywords

Amyotrophic lateral sclerosis MRI Diffusion tensor imaging Clinical trials Axonal degeneration 

Notes

Acknowledgements

This work was supported by funding to Forefront, a collaborative research group dedicated to the study of motor neurone disease, from the National Health and Medical research Council of Australia Program Grant (#1037746). We are grateful to the research participants involved with the ForeFront research studies.

Compliance with ethical standards

Conflicts of interest

Dr. Simon, Dr. Lagopoulos, Ms. Paling, Dr. Pfluger, Dr. Park, Dr. Howells, Dr. Gallagher, Dr. Kliot, Dr. Henderson, Dr. Vucic reports no disclosures. Dr. Kiernan serves as the editor-in-chief of Journal of Neurology, Neurosurgery and Psychiatry.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Neil G. Simon
    • 1
  • Jim Lagopoulos
    • 2
  • Sita Paling
    • 3
  • Casey Pfluger
    • 4
  • Susanna B. Park
    • 5
  • James Howells
    • 5
  • Thomas Gallagher
    • 6
  • Michel Kliot
    • 7
  • Robert D. Henderson
    • 8
  • Steve Vucic
    • 9
  • Matthew C. Kiernan
    • 5
  1. 1.St Vincent’s Clinical SchoolUniversity of New South WalesDarlinghurstAustralia
  2. 2.Sunshine Coast Mind and Neuroscience-Thomson InstituteUniversity of the Sunshine CoastBirtinyaAustralia
  3. 3.Faculty of ScienceUniversity of SydneySydneyAustralia
  4. 4.Centre for Clinical Research, School of MedicineThe University of QueenslandBrisbaneAustralia
  5. 5.Brain and Mind Centre, Sydney Medical SchoolUniversity of SydneyCamperdownAustralia
  6. 6.Department of RadiologyNorthwestern Feinberg School of MedicineChicagoUSA
  7. 7.Department of NeurosurgeryStanford Neurosience Health CenterPalo AltoUSA
  8. 8.Department of NeurologyRoyal Brisbane and Women’s HospitalBrisbaneAustralia
  9. 9.Westmead Clinical School, C24 Westmead HospitalThe University of SydneySydneyAustralia

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