P 28 Voxel-based Morphometry (VBM) subcortical white matter changes correlate with disease progression in amyotrophic lateral sclerosis

Abstract

Introduction Amyotrophic lateral sclerosis (ALS) is a progressive, multisystemic disorder.Signs of lower motor neurone involvement are readily detectable but the involvement of the upper motor neurone is elusive.Hence, we must identify the extent and development of ALS related changes in the brain in different subtypes of ALS to facilitate an early diagnosis and stratification for clinical trials.Previous studies applying Voxel-based morphometry (VBM) provided inconsistent results. Objective The aim of this study is to describe the heterogeneity of ALS with regard to the site of onset (bulbar vs.limb), disease duration (long vs.short), degree of disability (high vs.low) and disease progression rate (rapid vs.slow) in a large cohort of well characterized ALS patients.ALS related MRI changes should correlate with clinical parameters, such as ALSFRS-R score and D50 (50% disease progression in a model of sigmoidal decay of the ALSFRS-R). The long-term aim of this study is to evaluate VBM as a predictive marker for ALS in a representative number of subjects ( n > 100 ). Methods High resolution T1-weighted FLASH 3D scans (fl3d) in 92 ALS patients and 62 healthy controls were analyzed using VBM8 in SPM8 on matlab 2009b.Clinical parameters were collected regularly: disease duration, date and location of the first symptom, rate of disease progression and degree of disability (ALSFRS-R). Based on these clinical parameters, patients were classified into the subgroups and analyzed to determine changes in the gray and white matter. Results The mean age of 62 controls was 53.97y and of the 92 patients 60.24y.The patient group included 24 bulbar and 68 limb onsets.Average disease duration was 25 mo, wherein 26 patients had a long ( ⩾ 24mo) and 35 had a short ( ⩽ 12mo) disease duration.Mean ALSFRS-R was 37.8.46 patients had a “low” degree of disability (ALSFRS-R ⩾ 40), whereas 17 patients were “highly” impaired ( ⩽ 30).Mean progression rate was 0.66.A subgroup with a rapid form of ALS included 16 patients, with a slow form 46.Using VBM, more rapid progression, longer disease duration and more severely affected patients had a more pronounced reduction in GMV in the central, and frontal brain regions, whereas subcortical WM was more severely altered. Conclusion Using VBM in high resolution T1 in a large cohort of ALS patients, we were able to identify the key regions of ALS pathology which correlated well with three clinical progression parameters.It is likely that previous studies were underpowered and ALS related heterogeneity obscured the relevant pathology in computerized voxel-based analyses. Acknowledgement This research is supported by BMBF (Bundesministerium fur Bildung and Forschung) in the framework of the E-RARE programme (PYRAMID) and JPND (OnWebDUALS and SOPHIA) of the European Union in collaboration with the Neuroimaging Society in ALS (NiSALS) MRI repository Jena.