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Research paper
Structural MRI correlates of amyotrophic lateral sclerosis progression
  1. Joe Senda1,2,
  2. Naoki Atsuta1,
  3. Hirohisa Watanabe1,3,
  4. Epifanio Bagarinao3,
  5. Kazunori Imai1,
  6. Daichi Yokoi1,
  7. Yuichi Riku1,
  8. Michihito Masuda1,
  9. Ryoichi Nakamura1,
  10. Hazuki Watanabe1,
  11. Mizuki Ito1,
  12. Masahisa Katsuno1,
  13. Shinji Naganawa3,4,
  14. Gen Sobue1,5
  1. 1 Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
  2. 2 Department of Neurology and Rehabilitation, Komaki City Hospital, Komaki, Aichi, Japan
  3. 3 Brain and Mind Research Center, Nagoya University, Nagoya, Aichi, Japan
  4. 4 Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
  5. 5 Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
  1. Correspondence to Professor Gen Sobue, Department of Neurology and Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.; sobueg{at}med.nagoya-u.ac.jp

Abstract

Purpose Amyotrophic lateral sclerosis (ALS) presents with varying degrees of brain degeneration that can extend beyond the corticospinal tract (CST). Furthermore, the clinical course and progression of ALS varies widely. Brain degeneration detected using structural MRI could reflect disease progression.

Subjects and methods On study registration, 3-Tesla volumetric MRI and diffusion tensor imaging scans were obtained at baseline in 38 healthy controls and 67 patients with sporadic ALS. Patients had Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores of ≥36 and did not have the chromosome 9, open reading frame 72 repeat expansion. Six months later, changes in ALSFRS-R (ΔALSFRS-R) scores were calculated and patients were grouped into three categories, namely, patients with slow progression with ΔALSFRS-R scores ≤3 (n=19), intermediate progression with ΔALSFRS-R scores =4, 5 and 6 (n=36) and rapid progression with ΔALSFRS-R scores ≥7 (n=12). We analysed voxel-based morphometry and tract-based spatial statistics among these subgroups and controls.

Results In comparison with controls, patients with ALS showed grey matter atrophy and decreased fractional anisotropy beyond the motor cortex and CST, especially in the frontotemporal lobes and basal ganglia. Moreover, the degree of change was highly proportional to ΔALSFRS-R at the 6-month assessment.

Conclusion A more rapid disease progression and poorer functional decline were associated with greater involvement of the extra-motor cortex and basal ganglia, suggesting that the spatial extent of brain involvement can be an indicator of the progression in ALS.

  • amyotrophic lateral sclerosis (ALS)
  • progression
  • voxel-based morphometry (VBM)
  • diffusion tensor imaging (DTI)
  • fractional anisotropy (FA)

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Footnotes

  • Contributors JS, NA, HiW, KI, DY, YR, MM, RN, HaW, MI, MK, SN and GS were involved in data collection. JS, HiW and EB took part in analysis and interpretation of data and drafting of the manuscript. JS, NA, HiW, EB, KI, DY, YR, MM, RN, HaW, MI, MK, SN and GS were involved in conceptualisation of the study and manuscript revision.

  • Competing interests None declared.

  • Ethics approval Nagoya University Graduate School of Medicine.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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