Quantitative magnetic resonance neurographic characterization of peripheral nerve involvement in manifest and pre-ataxic spinocerebellar ataxia type 3

Abstract

Background and purposeKnowledge about the exact underlying pathophysiological changes involved in the genesis and progression of spinocerebellar ataxia type 3 (SCA3) is limited. Lower extremity peripheral nerve lesions in clinically, genetically and electrophysiologically classified ataxic and pre-ataxic SCA3 mutation carriers were characterized and quantified by magnetic resonance neurography (MRN).MethodsEighteen SCA3 mutation carriers and 20 age-/sex-matched healthy controls were prospectively enrolled. All SCA3 mutation carriers underwent detailed neurological and electrophysiological examinations. 3 T MRN covered the lumbosacral plexus and proximal thigh to the tibiotalar joint by using T2-weighted inversion recovery sequences, dual-echo relaxometry sequences with spectral fat saturation, and two gradient-echo sequences with and without an off-resonance saturation rapid frequency pulse. Detailed quantification of nerve lesions by morphometric and microstructural MRN markers, including T2 relaxometry and magnetization transfer contrast imaging, was conducted in all study participants.ResultsMRN detected peripheral nerve damage in ataxic and pre-ataxic SCA3. The quantitative markers proton spin density (ρ), T2 relaxation time, magnetization transfer ratio and cross-sectional area were decreased in SCA3, indicating chronic axonopathy. MTR and ρ identified early, subclinical nerve damage in pre-ataxic SCA3 and in SCA3 mutation carriers without polyneuropathy and were superior in differentiating between all subgroups. Additionally, microstructural markers correlated well with clinical symptom scores and electrophysiological results.ConclusionsOur data provide a comprehensive characterization of peripheral nerve damage in SCA3 and assist in understanding the mechanisms of the multisystemic disease evolution. Evidence of peripheral nerve involvement prior to the onset of clinically overt ataxia might have important implications for designing early intervention studies.Peripheral nerve involvement was characterized and quantified in 18 adult ataxic and pre-ataxic spinocerebellar ataxia type 3 (SCA3) mutation carriers in comparison with 20 healthy age- and sex-matched controls by applying high-resolution magnetic resonance neurography (MRN). The quantitative MRN markers proton spin density, T2 relaxation time, magnetization transfer ratio and cross-sectional area were decreased in SCA3, indicating a chronic axonopathy, and correlated well with clinical symptom scores and electrophysiological results. Early subclinical nerve damage in pre-ataxic SCA3 and in SCA3 mutation carriers without polyneuropathy was already evident and detectable by magnetization transfer ratio and proton spin density, having potentially important implications for designing future early intervention studies.