Multi-shell, multi-tissue (MSMT) constrained spherical deconvolution (CSD) allows precise white matter tract reconstructions in healthy brains. However, its implications for connectivity mapping in multiple sclerosis (MS) are unknown. Here we compare MSMT-CSD versus single-shell single-tissue (SSST)-CSD algorithms over different clinically-feasible diffusion-weighted protocols regarding their ability to reconstruct connectivity metrics that distinguish patients with a first inflammatory-demyelinating episode (n=19) from controls (n=12). Methodical analysis of data from time- and directionality-matched protocols showed that a greater angular resolution improves results and is preferable to choosing multi-tissue-CSD algorithms. Given similar angular resolution, all algorithms perform similarly, producing highly reproducible brain connectivity metrics.