Percutaneous thermal radiofrequency rhizotomy of L2-S1 spinal nerve roots in children with cerebral palsy.

OBJECTIVE: This study presents the results of an evaluation of the effectiveness of percutaneous thermal radiofrequency (RF) ablation of spinal nerve roots to reduce spasticity and improve motor function in children with cerebral palsy (CP). METHODS: A retrospective analysis was conducted on the surgical treatment outcomes of 26 pediatric patients with severe CP (Gross Motor Function Classification System levels IV-V). The assessment protocol included muscle tone assessment using the modified Ashworth scale (MAS), evaluation of passive and active range of motion, gait video recording, and locomotor status evaluation using the Gross Motor Function Measure (GMFM)-88 scale. Thermal RF rhizotomy (ablation of spinal nerve roots) was performed on all patients at the L2-S1 levels at 70°C for 90 seconds. The statistical data analysis was conducted using the t-test and Mann-Whitney U-test. A p value < 0.05 was considered statistically significant. RESULTS: Before the operation, the average level of spasticity in the lower-limb muscles of all patients was 3.0 ± 0.2 according to the MAS. In the early postoperative period, the spasticity level in all examined muscle groups significantly decreased to a mean of 1.14 ± 0.15 (p < 0.001). In the long-term postoperative period, the spasticity level in the examined muscle groups averaged 1.49 ± 0.17 points on the MAS (p < 0.001 compared to baseline, p = 0.0416 compared to the early postoperative period). Despite the marked reduction of spasticity in the lower limbs, no significant change in locomotor status according to the GMFM-88 scale was observed in the selected category of patients. In the long-term period, during the control examination of patients, the GMFM-88 level increased on average by 3.6% ± 1.4% (from 22.2% ± 3.1% to 25.8% ± 3.6%). CONCLUSIONS: The findings of this study offer preliminary yet compelling evidence that RF ablation of spinal nerve roots can lead to a significant and enduring decrease in muscle tone among children with severe spastic CP. Further studies and longer-term data of the impact on functionality and quality of life of patients with CP after spinal root RF ablation are needed.

Regulation of autophagy of the heart in ischemia and reperfusion.

Ischemia/reperfusion (I/R) of the heart leads to increased autophagic flux. Preconditioning stimulates autophagic flux by AMPK and PI3-kinase activation and mTOR inhibition. The cardioprotective effect of postconditioning is associated with activation of autophagy and increased activity of NO-synthase and AMPK. Oxidative stress stimulates autophagy in the heart during I/R. Superoxide radicals generated by NADPH-oxidase acts as a trigger for autophagy, possibly due to AMPK activation. There is reason to believe that AMPK, GSK-3ß, PINK1, JNK, hexokinase II, MEK, PKCα, and ERK kinases stimulate autophagy, while mTOR, PKCδ, Akt, and PI3-kinase can inhibit autophagy in the heart during I/R. However, there is evidence that PI3-kinase could stimulate autophagy in ischemic preconditioning of the heart. It was found that transcription factors FoxO1, FoxO3, NF-κB, HIF-1α, TFEB, and Nrf-2 enhance autophagy in the heart in I/R. Transcriptional factors STAT1, STAT3, and p53 inhibit autophagy in I/R. MicroRNAs could stimulate and inhibit autophagy in the heart in I/R. Long noncoding RNAs regulate the viability and autophagy of cardiomyocytes in hypoxia/reoxygenation (H/R). Nitric oxide (NO) donors and endogenous NO could activate autophagy of cardiomyocytes. Activation of heme oxygenase-1 promotes cardiomyocyte tolerance to H/R and enhances autophagy. Hydrogen sulfide increases cardiac tolerance to I/R and inhibits apoptosis and autophagy via mTOR and PI3-kinase activation.

KATP channels are regulators of programmed cell death and targets for the creation of novel drugs against ischemia/reperfusion cardiac injury.

BACKGROUND: The use of percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is associated with a mortality rate of 5%-7%. It is clear that there is an urgent need to develop new drugs that can effectively prevent cardiac reperfusion injury. ATP-sensitive K+ (KATP ) channel openers (KCOs) can be classified as such drugs. RESULTS: KCOs prevent irreversible ischemia and reperfusion injury of the heart. KATP channel opening promotes inhibition of apoptosis, necroptosis, pyroptosis, and stimulation of autophagy. KCOs prevent the development of cardiac adverse remodeling and improve cardiac contractility in reperfusion. KCOs exhibit antiarrhythmic properties and prevent the appearance of the no-reflow phenomenon in animals with coronary artery occlusion and reperfusion. Diabetes mellitus and a cholesterol-enriched diet abolish the cardioprotective effect of KCOs. Nicorandil, a KCO, attenuates major adverse cardiovascular event and the no-reflow phenomenon, reduces infarct size, and decreases the incidence of ventricular arrhythmias in patients with acute myocardial infarction. CONCLUSION: The cardioprotective effect of KCOs is mediated by the opening of mitochondrial KATP (mitoKATP ) and sarcolemmal KATP (sarcKATP ) channels, triggered free radicals' production, and kinase activation.

Apelin Is a Prototype of Novel Drugs for the Treatment of Acute Myocardial Infarction and Adverse Myocardial Remodeling.

In-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) is 5-6%. Consequently, it is necessary to develop fundamentally novel drugs capable of reducing mortality in patients with acute myocardial infarction. Apelins could be the prototype for such drugs. Chronic administration of apelins mitigates adverse myocardial remodeling in animals with myocardial infarction or pressure overload. The cardioprotective effect of apelins is accompanied by blockage of the MPT pore, GSK-3ß, and the activation of PI3-kinase, Akt, ERK1/2, NO-synthase, superoxide dismutase, glutathione peroxidase, matrix metalloproteinase, the epidermal growth factor receptor, Src kinase, the mitoKATP channel, guanylyl cyclase, phospholipase C, protein kinase C, the Na+/H+ exchanger, and the Na+/Ca2+ exchanger. The cardioprotective effect of apelins is associated with the inhibition of apoptosis and ferroptosis. Apelins stimulate the autophagy of cardiomyocytes. Synthetic apelin analogues are prospective compounds for the development of novel cardioprotective drugs.

Pharmacological Approaches to Limit Ischemic and Reperfusion Injuries of the Heart: Analysis of Experimental and Clinical Data on P2Y12 Receptor Antagonists.

Ischemic and reperfusion injuries of the heart underlie the pathogenesis of acute myocardial infarction (AMI) and sudden cardiac death. The mortality rate is still high and is 5-7% in patients with ST-segment elevation myocardial infarction. The review is devoted to pharmacological approaches to limitation of ischemic and reperfusion injuries of the heart. The article analyzes experimental evidence and the clinical data on the effects of P2Y12 receptor antagonists on the heart's tolerance to ischemia/reperfusion in animals with coronary artery occlusion and reperfusion and also in patients with AMI. Chronic administration of ticagrelor prevented adverse remodeling of the heart. There is evidence that sphingosine-1-phosphate is the molecule that mediates the infarct-reducing effect of P2Y12 receptor antagonists. It was discussed a role of adenosine in the cardioprotective effect of ticagrelor.

Endoscopic third ventriculostomy in patients younger than 2 years: outcome analysis of 41 hydrocephalus cases.

OBJECT: The object of this study was to analyze the outcome of endoscopic third ventriculostomy (ETV) in patients under 2 years of age and investigate factors related to ETV success or failure in this patient population. METHODS: The authors reviewed their experience in using endoscopic third ventriculostomy (ETV) in the treatment of 41 hydrocephalus patients younger than 2 years. The mean duration of follow-up was 45 months. The relationship between ETV efficacy and the following variables was analyzed: cause of hydrocephalus, level of CSF occlusion, primary versus secondary ETV, type of surgical procedure, head circumference, patient age at ETV, patient age at first manifestation of hydrocephalus, and anatomical features of the ventricle. Success of ETV was assessed based on the results of neurological examination and postoperative imaging during the follow-up period. RESULTS: The authors performed 32 primary ETVs and 10 secondary ETVs (ETV after hydrocephalus surgery) in 41 patients (a second ETV was performed in 1 patient). The success rates of primary and secondary ETV were 75.8 and 55.6%, respectively (no significant difference, p = 0.15). The ETV was clinically and radiologically successful in 30 (71.4%) of 42 procedures during a mean (+/- SD) follow-up period of 45.0 +/- 4.8 months (range 12-127 months). A negative relationship was found between success of ETV and the thickness of the floor of the third ventricle (the most effective procedures were those in which the floor of the ventricle was thinnest [p < 0.05]). There was a highly significant correlation between ETV success and prolapse of the ventricle floor (p < 0.001). Also, there was an inverse relationship between ventricle floor thickness and the width of the third ventricle (p < 0.005). In our group of patients there was significant correlation between ETV success and patient age at onset of hydrocephalus (the most effective procedures were in patients in whom signs of hydrocephalus first occurred after 1 month of age [p = 0.02]). CONCLUSIONS: Endoscopic third ventriculostomy was successful in 71.4% of procedures in children younger than 2 years and in 75.0% of procedures in infants. Success of ETV in children younger than 2 years depends not on the age of the patient or cause of hydrocephalus but on the thickness of the floor of the third ventricle and the patient's age at first manifestation of hydrocephalus.