Background/Objectives: Persons with disorders of consciousness (DoCs) may perceive pain without being able to communicate their discomfort. The Nociception Coma Scale (NCS) and its revised form (NCS-R) have been proposed to assess nociception in persons with DoCs. The main aim of this international multicenter study was to confirm (or not) our preliminary results and compare the NCS-R scores of standard stimulus (NCS-R-SS) to scores of personalized painful stimuli (NCS-R-PS). A secondary aim of the study was to verify possible correlations between the NCS-R-PS and Coma Recovery Scale—Revised (CRS-R) and to estimate convergent validity. Methods: Sixty-one patients with prolonged DoCs (pDoCs) were enrolled from seven European post-acute rehabilitation centers. Responsiveness and pain perception were assessed by CRS-R and NCS-R with standard stimulus (NCS-R-SS) and personalized stimulation (NCS-R-PS). ClinicalTrials.gov Identifier: NCT06012357. Results: our results support our prior findings on the superiority and the validity of the personalized painful stimulus approach in assessment of pain in persons with DoCs in comparison with the standardized pain assessment methodology. Conclusions: A more in-depth and tailored assessment of pain perception in persons with a DoC may lead to better acknowledgment of its presence and by extension an objective foundation for more aggressive and appropriate pain management.

The technique of transauricular vagus nerve stimulation (taVNS) is methodologically applied by placing electrodes on the auricular region, specifically on the cymba, cavum, or tragus, to stimulate the vagus nerve non-invasively. Additionally, the earlobe, which is not innervated by the vagus nerve, can serve as a placebo site for control stimulation. The stimulation intensity is adjusted between 0.5-3.0 mA, with session durations ranging from 20-60 min, administered either daily or weekly, depending on the study protocol. The total number of sessions varies according to the protocol, extending from a few weeks to several months. Ethically, research involving taVNS must adhere to regulations set by the local Agency for Medicines and Health Products and European Union guidelines. Approval from an Ethical Committee is required for studies involving healthy participants, while a Medical Ethical Committee is necessary for clinical research, ensuring that written information and informed consent are provided. Additionally, rigorous exclusion criteria must be established to safeguard participant safety, excluding pregnant individuals, those with cardiovascular, pulmonary, or metabolic diseases, psychiatric disorders, epilepsy, hypertension, or those using medications affecting the autonomic nervous system. In terms of clinical outcomes, the current study protocol demonstrated promising results with taVNS in patients with Disorders of Consciousness, showing significant improvement in alertness recovery and response to stimuli. Patients treated with taVNS experienced neurophysiological changes compared to the control group. Moreover, electroencephalographic biomarkers can be utilized to evaluate treatment efficacy, even in the absence of observable behavioral indicators. These findings suggest significant clinical potential for taVNS in managing Disorder of Consciousness, although the lack of specific regulations for taVNS underscores the need to adhere to international scientific best practices and seek consensus on European guidelines for its research application.

Background/Objectives: Stroke is a leading cause of disability, and post-stroke spasticity frequently impairs ankle mobility, strength, and gait. The gastrocnemius medialis (GM) is central to these deficits, yet the relationship between its ultrasound characteristics, functional outcomes, and spasticity severity remains unclear. This study aimed to compare structural and textural ultrasound features of the GM between individuals with chronic stroke presenting ankle spasticity and healthy controls, and to examine their associations with functional performance and spasticity severity. Methods: This case–control study included 26 individuals with stroke and 26 matched controls. Ultrasound assessments were performed using B-mode imaging to obtain parameters such as muscle thickness, pennation angle, and textural features (first-, second-, and higher-order). Functional measures included mobility (Timed Up and Go), walking speed (10-Meter Walk Test), ankle strength (dynamometry), and range of motion (goniometry). Spasticity was evaluated separately using the Modified Ashworth Scale. Results: No significant differences in GM ultrasound parameters were observed between groups or limbs (p > 0.05). Participants with stroke showed significantly reduced dorsiflexion mobility and lower strength for both plantarflexors and dorsalflexors. Correlations between ultrasound parameters and functional measures were not statistically significant; however, the effect size was consistently small. Spasticity severity did not significantly influence ultrasound findings. Conclusions: GM ultrasound parameters did not distinguish participants with stroke from controls or meaningfully correlate with function or spasticity. Functional impairments may stem primarily from neural mechanisms and compensatory motor strategies rather than muscle alterations detectable by ultrasound.

The technique of transauricular vagus nerve stimulation (taVNS) is methodologically applied by placing electrodes on the auricular region, specifically on the cymba, cavum, or tragus, to stimulate the vagus nerve non-invasively. Additionally, the earlobe, which is not innervated by the vagus nerve, can serve as a placebo site for control stimulation. The stimulation intensity is adjusted between 0.5-3.0 mA, with session durations ranging from 20-60 min, administered either daily or weekly, depending on the study protocol. The total number of sessions varies according to the protocol, extending from a few weeks to several months. Ethically, research involving taVNS must adhere to regulations set by the local Agency for Medicines and Health Products and European Union guidelines. Approval from an Ethical Committee is required for studies involving healthy participants, while a Medical Ethical Committee is necessary for clinical research, ensuring that written information and informed consent are provided. Additionally, rigorous exclusion criteria must be established to safeguard participant safety, excluding pregnant individuals, those with cardiovascular, pulmonary, or metabolic diseases, psychiatric disorders, epilepsy, hypertension, or those using medications affecting the autonomic nervous system. In terms of clinical outcomes, the current study protocol demonstrated promising results with taVNS in patients with Disorders of Consciousness, showing significant improvement in alertness recovery and response to stimuli. Patients treated with taVNS experienced neurophysiological changes compared to the control group. Moreover, electroencephalographic biomarkers can be utilized to evaluate treatment efficacy, even in the absence of observable behavioral indicators. These findings suggest significant clinical potential for taVNS in managing Disorder of Consciousness, although the lack of specific regulations for taVNS underscores the need to adhere to international scientific best practices and seek consensus on European guidelines for its research application.

Background/Objectives: Auricular Vagal Neuromodulation Therapy (AVNT) constitutes a promising non-invasive therapeutic approach for Disorders of Consciousness (DoCs). However, evidence regarding its effectiveness remains limited. In this context, although the Mismatch Negativity (MMN) is a well-established neurophysiological index associated with recovery in DoCs, its modulation by AVNT has not yet been investigated. This study aimed to evaluate the effect of AVNT on MMN in DoCs. Methods: Forty-four participants with DoCs were evenly assigned to either an experimental or a control group, alongside twenty-two healthy participants used to establish normative data in neurotypical conditions. The latency, peak and peak-to-peak MMN amplitude were assessed as a complement to the Coma Recovery Scale Revised (CRS-R). Subsequently, only the experimental group received AVNT, followed by a second assessment across all groups. Results: The control group showed extensive changes across sessions in both peak and peak-to-peak amplitudes. In contrast, the experimental group exhibited a significant change only in peak amplitude for the fronto-central region, with no changes in peak-to-peak amplitude. Between-session changes in peak and peak-to-peak amplitudes differed between the control and healthy groups in the parieto-occipital region. After adjustment for the inter-session interval, the ANCOVA showed an overall group effect on peak-to-peak amplitude changes in the parieto-occipital and right regions. No differences were detected between the control and experimental groups or between the experimental and healthy groups. Finally, no significant effects were found for MMN latency. Conclusions: These findings could be compatible with a possible effect of AVNT, although the evidence remained insufficient to demonstrate a direct effect of the intervention.