Radial extracorporeal shock wave therapy for the management of spasticity in cerebral palsy: study protocol for a randomized controlled trial.

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.

Risk factors and outcome of epilepsy in adults with cerebral palsy or intellectual disability.

INTRODUCTION: Epilepsy is found in 10-60% of individuals with cerebral palsy (CP) and 5.5-35% with intellectual disability (ID). However, little is known about the long-term evolution of epilepsy among adults. The aim of the study is to describe the factors associated with epilepsy and its outcome in a population of adults with CP or ID. METHODS: This retrospective study reviewed the medical records of 306 individuals with CP/ID. All individuals underwent neurological, psychiatric, and neuropsychological follow-ups. RESULTS: In the cohort, 72.5% of the individuals had a CP diagnosis, with a mean age of 36.4 years (IQR 24.0-46.0). Epilepsy was present in 55.6% of the individuals and was associated with CP (p < 0.01), spastic subtype (p < 0.01), a higher degree of ID (p < 0.01), hemorrhagic and congenital malformation etiologies (p 0.011), abnormal neuroimaging (p < 0.01), and worse scores on motor and communication scales (p < 0.01). Drug-resistant epilepsy (DRE) (22.4%) was associated with higher scores on motor scales (p < 0.01). Additionally, 42.3% of the individuals who attempted antiseizure medication (ASM) withdrawal experienced recurrence, which was associated with epileptic activity on the electroencephalogram (EEG) (p 0.004). CONCLUSIONS: Epilepsy is a common comorbidity in adults with CP or ID and is associated with greater brain damage and a more severe phenotype. Seizure recurrence after ASM withdrawal occurred in half of the individuals and was associated with epileptic activity on the EEG.

Selective deuteration of [(pyridylmethyl)sulfinyl]benzimidazole antisecretory drugs. A NMR study where DMSO-d6 acts as deuteration agent.

The use of deuterated drug bioisosteres to obtain superior pharmacokinetic properties or to investigate biotransformations at the molecular level is a growing field of pharmaceutical research. This work presents a NMR study on the deuteration of three structurally related antisecretory proton-pump inhibitors, the sodium salts of esomeprazole, 1, pantoprazole, 2, and rabeprazole, 3. It has been found that the methylene adjacent to the sulfinyl group displays stereoselective deuteration when the sodium salts of these products are dissolved at room temperature in D2O or CD3OD, a process that also occurs very efficiently in DMSO-d6 (a solvent considered non-deuterating) if a catalytic amount of NaOH is added. The stereoselectivity of the deuteration is consequence of the asymmetry around the sulfur atom of the sulfinyl group, and the rate of the H-D exchange seems to be mainly related to the polarity of the solvents. In addition, unusually long-range (up to seven bonds) NMR deuterium isotopic effects on proton have been detected. Density Functional Theory (DFT) calculations (DFT/6-31G**) have been performed on the rotamers about the CH2SO bond of 1, as well as about the equivalent bond in its entiol, N-anion, and entiolate. Less conformers than possible were obtained in all cases indicating strong preference for some spatial dispositions. Computed NMR shielding agrees with the experimentally obtained chemical shifts and help in identifying the most accessible diastereotopic hydrogen.

Determination of the enantiomeric purity of the antiasthmatic drug montelukast by means of 1H NMR spectroscopy.

In order to define an enantioselective nuclear magnetic resonance (NMR) method for the antiasthmatic drug montelukast, a series of nine easily available products were evaluated as NMR chiral solvating agents (CSAs): D-dibenzoyltartaric acid, D-ditoluoyltartaric acid, (+)-camphorsulfonic acid, (S)-BINOL, (S)-3,3'-diphenyl-2,2'-binaphthyl-1,1'-diol, (R)-3,3''-di-9-anthracenyl-1,1''-bi-2-naphthol, (R)-3,3''-di-9-phenanthrenyl-1,1''-bi-2-naphthol, Pirkle's alcohol, and (-)-cinchonidine. It was proved that most of the studied agents constitute diastereomeric complexes with both drug enantiomers in CD2 Cl2 or CDCl3 solutions, thus permitting the direct (1)H NMR detection of the unwanted S-enantiomer, even at levels of 0.75%. (-)-Cinchonidine was found to be the more convenient CSA in terms of NMR enantiodiscrimination power and ease of experimental requirements. The final method was validated and applied to the fast monitoring of the optical purity of montelukast "in-process" samples, circumventing the need for tedious and slower analytical procedures like enantioselective chromatography or capillary electrophoresis. In addition, a method for the enantiopurity control of the commercial drug (montelukast sodium salt) was also established using (S)-BINOL as NMR CSA.

Use of (S)-BINOL as NMR chiral solvating agent for the enantiodiscrimination of omeprazole and its analogs.

The application of (S)-1,1'-binaphthyl-2,2'-diol as NMR chiral solvating agent (CSA) for omeprazole, and three of its analogs (lanso-, panto-, and rabe-prazole) was investigated. The formation of diastereomeric host-guest complexes in solution between the CSA and the racemic substrates produced sufficient NMR signal splitting for the determination of enantiomeric excesses by (1)H- or (19)F-NMR spectroscopy. Using of hydrophobic deuterated solvents was mandatory for obtaining good enantiodiscrimination, thus suggesting the importance of intermolecular hydrogen bonds in the stabilization of the complexes. The method was applied to the fast quantification of the enantiomeric purity of in-process samples of S-omeprazole.