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Background: Spasticity is the most common motor disorder in cerebral palsy (CP), and its management is complex, posing a significant challenge for the rehabilitation team. Radial extracorporeal shock wave therapy (rESWT) has emerged in recent years as an effective, non-invasive, and low-risk alternative for the management of spasticity in CP patients, with only minor side effects such as small bruises or discomfort during application. There is great variability in rESWT administration protocols, ranging from a single session up to the 12 sessions. The most extensively studied protocol involves 3 rESWT sessions with a one-week interval between session. According to current literature, the effect of rESWT has not been investigated by extending the time interval between sessions beyond 1 week to determine if therapeutic effects on spasticity can be prolonged over time. Methods: Following a power calculation using the minimal clinical important difference of our primary outcome (R2 of Modified Tardieu Scale), 72 patients will be included in the study. Enrolment is based upon inclusion/exclusion criteria outlined in the Methods section. Participants will be randomized in 3 groups. Each patient will receive 2000 impulses in the Triceps Sural muscle (distributed by all the plantar flexor muscles: soleus and gastrocnemius), at a 2.2 Bars pressure and a frequency of 8 Hz. The Control Group will receive 3 rESWT sessions with a time interval of 1 week between each session. The Experimental Group A will receive 3 rESTW sessions with a time interval of 2 weeks between each session and the Experimental Group B will receive 3 rESTW sessions with a time interval of 4 weeks between each session. Discussion: This study will provide further information regarding the effect of rESWT on spasticity in patients with CP. If an increase in the time interval between rESWT sessions allows for the prolongation of therapeutic benefits on spasticity, it will be clinically relevant fact. With the same treatment dosage, patients will be able to benefit from its effects for a longer period of time. Clinical trial registration: ClinicalTrials.gov, identifier NCT05702606.
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The combustion of fossil fuels, mainly by diesel engines, generates Diesel Exhaust Particles (DEP) which are the main source of Particulate Matter (PM), a major air pollutant in urban areas. These particles are a risk factor for stroke with 5.6% of cases attributed to PM exposure. Our aim was to evaluate the effect of DEP exposure on clot formation and lysis in the context of stroke. An ex-vivo clot formation and lysis turbidimetric assay has been conducted in human and mouse plasma samples from ischemic stroke or control subjects exposed to DEP or control conditions. Experimental DEP exposure was achieved by nasal instillation in mice, or by ex-vivo exposure in human plasma. Results show consistent pro-thrombogenic features in plasma after human ischemic stroke and mouse cerebral ischemia (distal MCAo), boosted by the presence of DEP. Otherwise, thrombolysis times were increased after ischemia in chronically exposed mice but not in the DEP exposed group. Finally, subjects living in areas with high PM levels presented accelerated thrombolysis compared to those living in low polluted areas. Overall, our results point at a disbalance of the thrombogenic/lytic system in presence of DEP which could impact on ischemic stroke onset, clot size and thrombolytic treatment.
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Background: Rehabilitation is still the only treatment available to improve functional status after the acute phase of stroke. Most clinical guidelines highlight the need to design rehabilitation treatments considering starting time, intensity, and frequency, according to the tolerance of the patient. However, there are no homogeneous protocols and the biological effects are under investigation. Objective: To investigate the impact of rehabilitation intensity (hours) after stroke on functional improvement and serum angiogenin (ANG) in a 6-month follow-up study. Methods: A prospective, observational, longitudinal, and multicenter study with three cohorts: strokes in intensive rehabilitation therapy (IRT, minimum 15 h/week) vs. conventional therapy (NO-IRT, <15 h/week), and controls subjects (without known neurological, malignant, or inflammatory diseases). A total of seven centers participated, with functional evaluations and blood sampling during follow-up. The final cohort includes 62 strokes and 43 controls with demographic, clinical, blood samples, and exhaustive functional monitoring. Results: The median (IQR) number of weekly hours of therapy was different: IRT 15 (15-16) vs. NO-IRT 7.5 (5-9), p < 0.01, with progressive and significant improvements in both groups. However, IRT patients showed earlier improvements (within 1 month) on several scales (CAHAI, FMA, and FAC; p < 0.001) and the earliest community ambulation achievements (0.89 m/s at 3 months). There was a significant difference in ANG temporal profile between the IRT and NO-IRT groups (p < 0.01). Additionally, ANG was elevated at 1 month only in the IRT group (p < 0.05) whereas it decreased in the NO-IRT group (p < 0.05). Conclusions: Our results suggest an association of rehabilitation intensity with early functional improvements, and connect the rehabilitation process with blood biomarkers.
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Background: Rehabilitation therapy is the only available treatment for stroke survivors presenting neurological deficits; however, the underlying molecules and mechanisms associated with functional/motor improvement during rehabilitation are poorly understood. Objective: Our aim is to study the modulation of angiogenin and endothelial progenitor cells (EPCs) as repair-associated factors in a cohort of stroke patients and mouse models of rehabilitation after cerebral ischemia. Methods: The clinical study included 18 ischemic strokes admitted to an intensive rehabilitation therapy (IRT) unit, 18 non-ischemic controls and brain samples from three deceased patients. Angiogenin and EPCs were measured in blood obtained before and up to 6 months after IRT together with an extensive evaluation of the motor/functional status. In parallel, C57BL/6 mice underwent middle cerebral artery occlusion, and the pasta matrix reaching-task or treadmill exercises were used as rehabilitation models. Angiogenin RNA expression was measured after 2 or 12 days of treatment together with cell counts from EPCs cultures. Results: Brain angiogenin was identified in both human and mouse tissue, whereas serum levels increased after 1 month of IRT in association with motor/functional improvement. EPC populations were increased after stroke and remained elevated during follow-up after IRT. The mouse model of rehabilitation by the task-specific pasta matrix exercise increased the number of EPCs at 2 days and increased angiogenin expression after 12 days of rehabilitation. Conclusions: Angiogenin and EPCs are modulated by rehabilitation after cerebral ischemia, suggesting that both angiogenin and EPCs could serve as biomarkers of improvement during rehabilitation or future therapeutic targets.
