The clinical case described represents a paradigmatic example of Spasticity-Plus Syndrome (SPS), in which an acute orthopedic event acted as a triggering or amplifying factor of a pre-existing cluster of symptoms, including spasticity, muscle spasms, and neuropathic pain. This case contributes to the clinical understanding of Spasticity-Plus Syndrome by exemplifying how a multifaceted symptom cluster—including spasticity, neuropathic pain, and bladder dysfunction—can emerge and worsen in the context of peripheral trauma in a patient with MS. Although this is a single-case report, it supports the application of the SPS framework in real-world clinical reasoning and personalized therapeutic planning, in line with the criteria proposed by Fernández et al. and Centonze et al. At the time of manuscript submission, the patient had completed 9 months of follow-up, during which she underwent quarterly scheduled interventions consisting of PENG, TAP, and erector spinae blocks. These procedures allowed for sustained symptom control following the initial PRF, although the analgesic and antispastic effects had gradually attenuated by the sixth month. A second PRF session targeting the PENG region and potentially the obturator nerve is currently planned. These longitudinal data support the notion that repeated peripheral neuromodulation may offer a feasible strategy for long-term management of SPS in selected MS patients. In this patient, hip prosthesis implantation likely increased both peripheral and central sensitization, contributing to the activation of hyperexcitable spinal circuits characteristic of SPS. This phenomenon can be explained by the pathophysiological theory proposed by Centonze et al., according to which the demyelination of small-diameter axons, susceptible to ephaptic transmission and conduction block, may lead to the overlap of irritative and deficit symptoms (2, 3). In this context, neuromodulation strategies are becoming increasingly relevant in the integrated treatment of SPS. Among the potential interventions, intrathecal baclofen therapy was also considered during the clinical course. However, after detailed explanation of the procedural aspects, the patient declined consent, expressing a preference for less invasive and more reversible approaches. This patient-centered decision contributed to the selection of peripheral neuromodulation, which offered a safer and well-tolerated alternative in this context. This choice was already mentioned in the manuscript and is now further clarified. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive techniques that have demonstrated efficacy in experimental settings in modulating cortical plasticity and reducing spasticity symptoms in patients with MS and other central nervous system lesions (8, 11, 12). However, these approaches mainly act at the supraspinal and cortical levels and have not yet been fully integrated into current clinical practice, with relatively limited effectiveness on aberrant segmental transmission and on exaggerated spinal reflexes that contribute to spasms and clonus (1–3). In this scenario, the rationale for the use of pulsed radiofrequency (PRF) may therefore be proposed—a non-destructive peripheral neuromodulation technique that differs from continuous radiofrequency by its lack of neurodestructive effects and its ability to selectively modulate the activity of sensory nerves (4, 13–18). PRF operates by generating short high-frequency electrical impulses at low temperatures (≤42 °C), which result in an alteration of the neuronal microenvironment, reducing membrane excitability and interfering with nociceptive signal transmission without causing structural damage (14). At the segmental level, PRF has been associated with a reduction in abnormal ephaptic transmission, suppression of neuronal hyperexcitability, and modulation of ion channels responsible for the propagation of action potentials in sensory neurons (14). These effects are particularly useful in patients with MS, in whom demyelination renders axons more susceptible to crosstalk phenomena. Scientific evidence exists to support the assertion that pulsed radiofrequency (PRF) can modulate segmental neuronal excitability, reduce abnormal ephaptic transmission, and influence ion channels involved in the propagation of action potentials in sensory neurons. A study published in Pain Physician highlighted that PRF modulates various ion channels, including Na⁺/K⁺ ATPase, HCN, and P2X3, in addition to affecting neurotransmitters and postsynaptic receptors such as AMPA-R and GABA-B (17). All these effects contribute to the reduction of nociceptive transmission and the attenuation of neuropathic pain (16–20). These comprehensive analysis showed that PRF induces microscopic and biochemical changes in neurons and glial cells, regulating inflammatory responses and gene expression related to pain transmission (19). These effects include modulation of structures such as myelin, mitochondria, and ion channels, contributing to the antinociceptive effect of PRF (16, 17, 19, 21). Beyond nociceptive modulation, recent preclinical studies suggest that PRF may attenuate microglial activation and reduce pro-inflammatory cytokines such as TNF-α and IL-1β. These effects might influence the neuroinflammatory milieu typical of MS and indirectly support oligodendrocyte survival and remyelination (22). While evidence in demyelinating disease models remains preliminary, such findings raise the possibility that PRF could impact immune-neural interactions relevant to the pathogenesis of Spasticity-Plus Syndrome (5, 20). From a practical standpoint, PRF presents as an advantageous technique for several reasons: it allows for focal and selective action on sensory branches (such as the trochanteric branches of the femoral and obturator nerves), has an excellent safety profile compared to continuous radiofrequency (which can cause thermal nerve injury), is easily repeatable over time, and provides significant pain relief that facilitates active participation in functional rehabilitation (16–19). In the case described, the combination of diagnostic nerve blocks followed by targeted pulsed radiofrequency (PRF) of the articular branches of the femoral and obturator nerves resulted in a clinical benefit greater than that achieved with pharmacologic therapy or botulinum toxin alone. This outcome supports both the clinical validity of the Spasticity-Plus Syndrome (SPS) construct and the therapeutic expansion of peripheral neuromodulation strategies such as PRF within a personalized, multimodal framework. The therapeutic role of pulsed radiofrequency (PRF) in neuropathic pain syndromes is well supported in both clinical and experimental literature. Beyond the single case context, PRF has been recognized in international guidelines, including those of the International Neuromodulation Society (INS) and the Neuromodulation Appropriateness Consensus Committee (NACC), as a valid and evidence-based tool for managing chronic neuropathic pain. Its non-destructive, focal mechanism of action and favorable safety profile make it especially suitable for integration into multimodal pain management protocols, particularly when pharmacological strategies have failed or caused intolerable side effects. Finally, this report is limited by the use of predominantly subjective outcome measures, including patient-reported improvements in pain, spasms, and sleep. While some clinical scales such as the Modified Ashworth Scale and Numerical Rating Scale were used at baseline, they were not consistently applied at each follow-up. Electrophysiological assessments, such as EMG or H-reflex, were not conducted. Future studies should incorporate standardized quantitative tools and objective neurophysiological indicators to strengthen evidence on the efficacy of PRF in Spasticity-Plus Syndrome.

This case underscores the importance of integrating neurophysiological assessments into the rehabilitative decision-making process, especially in complex or treatment-resistant presentations of central nervous system disorders. Infact, neurophysiology offers valuable insights into functional connectivity, fatigue mechanisms, and motor control, which can inform individualized rehabilitation strategies and optimize outcomes (21, 23, 24) (Figure 1).