Multidimensional Characterization of Parkinson’s Disease Subtypes Through Motor Neuron Excitability and Peripheral Immune Dynamics: Insights from F-Wave Modulation Metrics

<b>Background/Objective:</b> Central pathophysiological heterogeneity among Parkinson's disease (PD) motor subtypes has been increasingly recognized, yet subtype-specific peripheral disturbances are limited. We aimed to characterize demographic, biochemical, and neurophysiological differences among PD motor subtypes, evaluate hematoinflammatory effects on peripheral and proximal motor conduction, and identify prognostic phenotypic biomarkers. <b>Methods:</b> A total of 110 participants (60 idiopathic PD patients (30 akinetic-rigid (AR), 30 tremor-predominant (TD), and 50 age- and sex-matched healthy controls (HCs)) were enrolled. Demographic data, nerve conduction studies (NCS) including detailed F-wave analysis, and hematoinflammatory markers were collected. Kruskal-Wallis, linear mixed models, multivariable regression, and ROC analyses were applied. <b>Results:</b> Hematoinflammatory indices were elevated in both subtypes compared with HCs, with more pronounced changes in AR (mean platelet volume (MPV) H = 4.367, <i>p</i> = 0.003; systemic inflammatory response index (SIRI) H = 3.929, <i>p</i> = 0.004). AR showed severe upper-limb-predominant motor involvement (median motor onset latency H = 55.30, <i>p</i> < 0.001; amplitude H = 50.52, <i>p</i> = 0.04; conduction velocity H = 49.15, <i>p</i> < 0.001), whereas TD showed milder, lower-limb-predominant changes (tibial motor onset latency H = 19.89, <i>p</i> < 0.001; amplitude H = 51.50, <i>p</i> = 0.02; velocity H = 15.39, <i>p</i> < 0.001). AR also demonstrated prolonged minimal (Fmin)/mean (Fmean) ulnar F-wave latencies versus TD (respectively, H = 10.51, <i>p</i> = 0.001; H = 8.79, <i>p</i> = 0.003), with both showing increased tibial Fmean/Fmax latencies. Platelet-eosinophil indices independently predicted ulnar F-latencies (B = 0.104-0.105; <i>p</i> = 0.001; model R² = 0.21-0.39). Select F-wave metrics yielded ROC AUCs ≈ 0.65-0.92 (ulnar Fmin AUC ≈ 0.92 vs. HCs); AR achieved sensitivity/specificity ≈ 70-74%. <b>Conclusions:</b> The AR subtype showed increased hematoinflammatory changes, specifically in MPV and SIRI, as well as a tendency toward more pronounced proximal motor and peripheral nerve conduction impairment compared with TD. Platelet-eosinophil indices and F-wave metrics may represent potential candidate markers for diagnostic or stratification purposes in PD subtyping and could possibly aid in prognostic estimation.