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Midbrain morphology reflects extent of brain damage in Krabbe disease

  • Paediatric Neuroradiology
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Abstract

Introduction

To study the relationships between midbrain morphology, Loes score, gross motor function, and cognitive function in infantile Krabbe disease.

Methods

Magnetic resonance imaging (MRI) scans were evaluated by two neuroradiologists blinded to clinical status and neurodevelopmental function of children with early or late infantile Krabbe disease. A simplified qualitative 3-point scoring system based on midbrain morphology on midsagittal MRI was used. A score of 0 represented normal convex morphology of the midbrain, a score of 1 represented flattening of the midbrain, and a score of 3 represented concave morphology of the midbrain (hummingbird sign). Spearman correlations were estimated between this simplified MRI scoring system and the Loes score, gross motor score, and cognitive score.

Results

Forty-two MRIs of 27 subjects were reviewed. Analysis of the 42 scans showed normal midbrain morphology in 3 (7.1 %) scans, midbrain flattening in 11 (26.2 %) scans, and concave midbrain morphology (hummingbird sign) in 28 (66.7 %) scans. Midbrain morphology scores were positively correlated with the Loes score (r = 0.81, p < 0.001) and negatively correlated with both gross motor and cognitive scores (r = −.84, p < 0.001; r = −0.87, p < 0.001, respectively). The inter-rater reliability for the midbrain morphology scale was κ = .95 (95 % CI: 0.86–1.0), and the inter-rater reliability for the Loes scale was κ = .58 (95 % CI: 0.42–0.73).

Conclusions

Midbrain morphology scores of midsagittal MRI images correlates with cognition and gross motor function in children with Krabbe disease. This MRI scoring system represents a simple but reliable method to assess disease progression in patients with infantile Krabbe disease.

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Acknowledgments

We acknowledge NIH/NINDS R01 NS061965-01, the DANA foundation and The Legacy of Angels Foundation.

Ethical standards and patient consent

We declare that all human and animal studies have been approved by the UPMC IRB and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. We declare that all patients gave informed consent prior to inclusion in this study.

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Section of Neuroradiology, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Giulio Zuccoli, Srikala Narayanan & Ashok Panigrahy

  2. Program for the Study of Neurodevelopment in Rare Disorders, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center, University of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA

    Michele D. Poe & Maria L. Escolar

Authors
  1. Giulio Zuccoli
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  2. Srikala Narayanan
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  3. Ashok Panigrahy
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  4. Michele D. Poe
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  5. Maria L. Escolar
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Corresponding author

Correspondence to Maria L. Escolar.

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Zuccoli, G., Narayanan, S., Panigrahy, A. et al. Midbrain morphology reflects extent of brain damage in Krabbe disease. Neuroradiology 57, 739–745 (2015). https://doi.org/10.1007/s00234-015-1523-7

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  • DOI: https://doi.org/10.1007/s00234-015-1523-7

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