Beyond proportional recovery in wake-up stroke: unsupervised recovery clusters based on the NIHSS

Post-stroke rehabilitation is a complex process influenced by several neurophysiological factors. The recovery is traditionally predicted based on initial impairment using linear models. The Proportional Recovery Rule (PRR), developed on the Fugl-Meyer scale, has even been proposed as a therapeutic target. In this framework, patients are classified as "fitters" or "non-fitters", though this distinction depends on the methodology used. Additionally, issues like mathematical coupling and ceiling effects on clinical scales could raise concerns about the validity of these models. To overcome these issues, Repeated Spectral Clustering (RSC) was used to identify recovery patterns based on NIHSS. We selected 201 patients from the WAKE-UP trail, all moderately impaired at onset and still impaired at 22-36 h. Clustering was performed using a similarity matrix based on pairwise absolute differences between recovery ratios, calculated from 22-36 h to 90 days post-stroke. Cluster differences were tested with prognostic factors, including lesion volume, side, treatment, and the Heidelberg scale. The PRR was fit to the cohort for comparison with clustering results. The linear fit reproduced findings consistent with the literature, such as a correlation of [Formula: see text] and an average recovery ratio of 70% for the "fitters". RSC grouped patients into six recovery clusters: [Formula: see text] (full recovery), [Formula: see text] (above average), [Formula: see text] and [Formula: see text] (average, PRR-aligned), [Formula: see text] (below average), and [Formula: see text] (deterioration). NIHSS scores in most patients declined non-proportionally. Lesion volume was not significantly different across clusters, while left-sided strokes were higher in low recovery clusters. Patients with a recovery ratio [Formula: see text] within two weeks mostly fell into favorable clusters ([Formula: see text]-[Formula: see text]), covering [Formula: see text] of such cases. The identified clusters provide a refined view of stroke recovery following wake-up stroke. Clustering better captures patient similarities, enabling the assessment of neurophysiological differences between groups and supporting tailored interventions.