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Observational Study
. 2021 Jun;8(6):1239-1250.
doi: 10.1002/acn3.51352. Epub 2021 May 5.

Scoliosis in Friedreich's ataxia: longitudinal characterization in a large heterogeneous cohort

Christian Rummey  1 , John M Flynn  2 , Louise A Corben  3   4 , Martin B Delatycki  3   4 , George Wilmot  5 , Sub H Subramony  6 , Khalaf Bushara  7 , Antoine Duquette  8 , Christopher M Gomez  9 , J Chad Hoyle  10 , Richard Roxburgh  11 , Lauren Seeberger  12 , Grace Yoon  13 , Katherine D Mathews  14 , Theresa Zesiewicz  15 , Susan Perlman  16 , David R Lynch  17
Affiliations
Observational Study

Scoliosis in Friedreich's ataxia: longitudinal characterization in a large heterogeneous cohort

Christian Rummey et al. Ann Clin Transl Neurol. 2021 Jun.

Abstract

Objective: The objective of this study was to characterize the incidence and progression of scoliosis in the natural history of Friedreich's ataxia (FRDA) and document the factors leading to the requirement for corrective surgery.

Methods: Data on the prevalence of scoliosis and scoliosis surgery from up to 17 years of follow-up collected during a large natural history study in FRDA (1116 patients at 4928 visits) were summarized descriptively and subjected to time to event analyses.

Results: Well over 90% of early or typical FRDA patients (as determined by age of onset) developed intermediate to severe scoliosis, while patients with a later onset (>14 years) had no or much lower prevalence of scoliosis. Diagnosis of scoliosis occurs during the onset of ataxia and in rare cases even prior to that. Major progression follows throughout the growth phase and puberty, leading to the need for surgical intervention in more than 50% of individuals in the most severe subgroup. The youngest patients appear to delay surgery until the end of the growth period, leading to further progression before surgical intervention. Age of onset of FRDA before or after reaching 15 years sharply separated severe and relatively mild incidence and progression of scoliosis.

Interpretation: Scoliosis is an important comorbidity of FRDA. Our comprehensive documentation of scoliosis progression in this natural history study provides a baseline for comparison as novel treatments become available.

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Conflict of interest statement

The authors report no relevant disclosures.

Figures

Figure 1
Figure 1
Categorized degree of scoliosis by age of onset, age, and curvature angle. The number of observations is given below the bars (note differential width of age bins).
Figure 2
Figure 2
Age at diagnosis of scoliosis (Turnbull estimates).
Figure 3
Figure 3
Age at corrective surgery (Kaplan Meier estimates).
Figure 4
Figure 4
Disease duration at corrective surgery (Kaplan Meier estimates). Surgeries occurring before onset of first symptoms of FRDA were set to time 0 (mainly onset group 15–24 years).
Figure 5
Figure 5
Age at corrective surgery (Kaplan Meier estimates), by GAA repeat length (shorter allele).
Figure 6
Figure 6
Age at corrective surgery (Kaplan Meier estimates), by sex and age of onset.
Figure 7
Figure 7
Time to loss of ambulation, relative to scoliosis surgery.
See this image and copyright information in PMC

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