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Flow-metabolism uncoupling in the cervical spinal cord of ALS patients

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Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. In ALS, both glucose consumption and neuronal intensity reportedly decrease in the cerebral motor cortex when measured by positron emission tomography (PET). In this study, we evaluated cervical spinal glucose metabolism, blood flow, and neuronal intensity of 10 ALS patients with upper extremity (U/E) atrophy both with 18F-2-fluoro-2-deoxy-d-glucose (18F-FDG) PET and 11C-flumazenil (11C-FMZ) PET. On the ipsilateral side of C5 and T1 levels, 18F-FDG uptake increased significantly (*p < 0.05), and was correlated with the rate of progression of the ALS FRS-R-U/E score (R = 0.645, *p = 0.041). Despite this hyperglucose metabolism, the 11C-FMZ PET study did not show a coupled increase of spinal blood flow even though neuronal intensity did not decrease. These results indicate a strong correlation between hyperglucose metabolism and ALS progression alongside the uncoupling of flow-metabolism. This mechanism, which could result in subsequent motor neuronal death, may be a potential therapeutic target for ALS.

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Abbreviations

ALS:

Amyotrophic lateral sclerosis

ALS FRS-R:

ALS functional rating scale-revised

11C-FMZ:

11C-flumazenil

18F-FDG:

18F-2-fluoro-2-deoxy-d-glucose

FOV:

Field of view

NVU:

Neurovascular unit

PET:

Positron emission tomography

ROI:

Regions of interest

SBF:

Spinal blood flow

SUV:

Standardized uptake value

U/E:

Upper extremity

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Acknowledgements

This work was partly supported by a Grant-in-Aid for Scientific Research (B) 25293202, (C) 15K09316 and Challenging Research 15K15527 and Young Research 15K21181, and by Grants-in-Aid from the Research Committees (Mizusawa H, Nakashima K, Nishizawa M, Sasaki H, and Aoki M) from the Ministry of Health, Labour and Welfare of Japan.

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Authors and Affiliations

  1. Department of Neurology, Graduate School of Medicine, Dentistry and Pharmacy, Okayama University, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan

    Toru Yamashita, Kota Sato, Yusuke Fukui, Nozomi Hishikawa, Yasuyuki Ohta & Koji Abe

  2. Department of Neurological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Tetsuhiro Hatakeyama & Takashi Tamiya

  3. Department of Radiology, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Yoshihiro Nishiyama

  4. Department of Neurological Surgery, Kagawa General Rehabilitation Hospital, Kagawa, Japan

    Nobuyuki Kawai

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  1. Toru Yamashita
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  2. Tetsuhiro Hatakeyama
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Correspondence to Koji Abe.

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Yamashita, T., Hatakeyama, T., Sato, K. et al. Flow-metabolism uncoupling in the cervical spinal cord of ALS patients. Neurol Sci 38, 659–665 (2017). https://doi.org/10.1007/s10072-017-2823-y

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  • DOI: https://doi.org/10.1007/s10072-017-2823-y

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