Neurophysiological assessment of disease severity in Friedreich's Ataxia: a study of brainstem auditory and visual evoked potentials.

OBJECTIVE

To evaluate a multimodal assessment including clinical rating scales, brainstem auditory evoked potentials (BAEPs), pattern reversal visual evoked potentials (p-VEPs), and serum biomarkers as candidate measures of disease severity in longstanding Friedreich's ataxia (FRDA).

METHODS

In a prospective, monocentric cohort, we conducted a cross-sectional baseline assessment of 29 genetically confirmed adult FRDA patients. Disease severity was rated with modified Friedreich Ataxia Rating Scale (mFARS). All underwent BAEPs and/or p-VEPs; available serum markers (NfL, NfH, GFAP, IL-6) were assayed. Associations with mFARS were tested using correlations and multiple linear regression adjusted for age and disease duration.

RESULTS

Neurophysiological abnormalities were frequent (p-VEPs 96.3% [26/27]; BAEPs 85.7% [24/28]). mFARS correlated with BAEP wave III latency (R = 0.70, p < 0.0001) and p-VEP N75 latency (R = 0.56, p = 0.002). A BAEP model predicted mFARS (F(4,13) = 13.70, p = 0.00014; adjusted R2 = 0.75), with disease duration (β = 0.64, p = 0.001) and wave III latency (β = 0.42, p = 0.007) as significant contributors. A p-VEP model also predicted mFARS (F(4,12) = 20.35, p = 0.0003; adjusted R2 = 0.83), with disease duration (β = 0.62, p = 0.001) and N75 latency (β = 0.45, p = 0.005). Patients with abnormal BAEPs had higher mFARS than those with normal BAEPs (U = 35.0, p = 0.03). mFARS differed across BAEP grades (H(4,N = 28) = 10.22, p = 0.04) and p-VEP grades (H(4,N = 27) = 11.39, p = 0.02). Serum biomarkers showed no consistent association with mFARS.

CONCLUSIONS

BAEPs and p-VEPs are highly prevalent and closely associated with clinical severity in chronic FRDA, outperforming tested serum biomarkers.

SIGNIFICANCE: Evoked potentials provide accessible, non-invasive, quantitative candidate biomarkers for severity assessment and longitudinal monitoring in FRDA, supporting their use in clinical practice and trial design when fluid markers are inconclusive.