BDNF as Predictor Biomarker for pediatric Cerebral Palsy patients
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ORGANISM(S): Homo sapiens (human)
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PROVIDER: S-BSST928 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:To characterize the population pharmacokinetics (PK) of oral baclofen and assess impact of patient-specific covariates in children with cerebral palsy (CP) in order to support its clinical use.Children (2-17 years of age) with CP received a dose of titrated oral baclofen from 2.5 mg 3 times a day to a maximum tolerated dose of up to 20 mg 4 times a day. PK sampling followed titration of 10-12 weeks. Serial R- and S-baclofen plasma concentrations were measured for up to 16 hours in 49 subjects. Population PK modeling was performed using NONMEM 7.1 (ICON PLC; Ellicott City, Maryland).R- and S-baclofen showed identical concentration-time profiles. Both baclofen enantiomers exhibited linear and dose/kg-proportional PK, and no sex differences were observed. Average baclofen terminal half-life was 4.5 hours. A 2-compartment PK model with linear elimination and transit absorption steps adequately described concentration-time profiles of both baclofen enantiomers. The mean population estimate of apparent clearance/F was 0.273 L/h/kg with 33.4% inter-individual variability (IIV), and the apparent volume of distribution (Vss/F) was 1.16 L/kg with 43.9% IIV. Delayed absorption was expressed by a mean transit time of 0.389 hours with 83.7% IIV. Body weight, a possible genetic factor, and age were determinants of apparent clearance in these children.The PK of oral baclofen exhibited dose-proportionality and were adequately described by a 2-compartment model. Our population PK findings suggest that baclofen dosage can be based on body weight (2 mg/kg per day) and the current baclofen dose escalation strategy is appropriate in the treatment of children with CP older than 2 years of age.
| S-EPMC3992203 | biostudies-literature
Project description:Purpose of review:a)Despite its widespread use, oral baclofen requires a critical review of the pharmacology to determine potential precision medicine applications to improve medication administration. Discussing the dose?exposure?response relationship of oral baclofen allows a conceptual framework in which designing clinical trials would become more successful. This paper seeks to examine some of the areas where variability in exposures can exist lead to undesired clinical responses. Recent findings:b)Several factors are at play to implement precision medicine with oral baclofen in the pediatric patient with cerebral palsy. Variations in intestinal absorption, oral baclofen clearance, pharmacogenomic variants, and distribution of this medication into the cerebrospinal fluid cause differences in the amount of baclofen available at the GABA-B receptor site to cause a clinical response. Summary:c)Oral baclofen has significant variability in disposition and clinical response. Research to determine the causes for this variability and controlling for these factors would allow improvement in clinical outcomes.
| S-EPMC6774387 | biostudies-literature
Project description:BackgroundNeuroradiological studies have greatly improved the knowledge and diagnoses of cerebral palsy with its underlying pathology, types and accompanying changes in brain morphology. However, there is no published study on cerebral palsy neuroimaging patterns in Ethiopia.MethodsRetrospective chart and neuroimaging reviews were conducted among pediatric patients, who attended Ayder Comprehensive Specialized Hospital between January 2016 and August 2019, fulfilling the study criteria. The magnetic resonance images and computed tomography scans reviewed by a neuroradiologist and/or pediatric neurologist were included. Data was collected using a structured checklist and analyzed using SPSS statistical software version 22. Results were represented using tables, graphs and images.ResultsThe median age at neuroimaging was 2 years. There were more males (54.5%) than females (45.5%) with a male: female ratio of 1.2:1. Majority of the patients had magnetic resonance (81.8%) as opposed to computed tomography scans (18.2%). Most of the patients (69.7%) had been born at term with spastic quadriplegia (33.3%) found to be the leading type of cerebral palsy. 30.3% of the patients had normal neuroimaging studies whereas 69.7% had neuroimaging abnormalities. Anomalies included pathologies of the white matter (18.2%), basal ganglia (15.2%), cortex and lobes (27.3%), corpus callosum (6.1%), lateral ventricles (12.1%), cysts (18.2%) and cerebellum (3%), respectively. Other findings were seen in 45.5% of the patients.ConclusionSevere forms of cerebral palsy (spastic quadriplegia) were most common with majorly cortical and subcortical brain involvement.
| S-EPMC7641380 | biostudies-literature
Project description:Cerebral palsy is caused be an upper motor neuron lesion which casues spasticity as well as secondary effects on muscle . Muscle from cerebral palsy patients is has been shown to be smaller, with more ECM and longer sarcomere lengths; We used microarrays to globally investigate the transcriptional adaptations of cerebral palsy muscle and research which muscle pathways are altered in the diseased state Experiment Overall Design: Muscle biopsies were taken from children undergoing surgery which exposed wrist muscle extensors (n=8) and flexors (n=8) in both cerebral palsy patients (n=6) and control patients (n=2) for RNA extraction and hybridization to Affymetrix GeneChips . Cerebral palsy patients were classified by a number of clinical scores.
2009-09-05 | E-GEOD-11686 | biostudies-arrayexpress
Project description:Cerebral palsy is caused be an upper motor neuron lesion which casues spasticity as well as secondary effects on muscle . Muscle from cerebral palsy patients is has been shown to be smaller, with more ECM and longer sarcomere lengths We used microarrays to globally investigate the transcriptional adaptations of cerebral palsy muscle and research which muscle pathways are altered in the diseased state Keywords: Disease state analysis
2009-08-26 | GSE11686 | GEO
Project description:Cerebral palsy (CP) is predominantly a disorder of movement, with evidence of sensory-motor dysfunction. CIMT1 is a widely used treatment for hemiplegic CP. However, effects of CIMT on somatosensory processing remain unclear. To examine potential CIMT-induced changes in cortical tactile processing, we designed a prospective study, during which 10 children with hemiplegic CP (5 to 8 years old) underwent an intensive one-week-long nonremovable hard-constraint CIMT. Before and directly after the treatment, we recorded their cortical event-related potential (ERP) responses to calibrated light touch (versus a control stimulus) at the more and less affected hand. To provide insights into the core neurophysiological deficits in light touch processing in CP as well as into the plasticity of this function following CIMT, we analyzed the ERPs within an electrical neuroimaging framework. After CIMT, brain areas governing the more affected hand responded to touch in configurations similar to those activated by the hemisphere controlling the less affected hand before CIMT. This was in contrast to the affected hand where configurations resembled those of the more affected hand before CIMT. Furthermore, dysfunctional patterns of brain activity, identified using hierarchical ERP cluster analyses, appeared reduced after CIMT in proportion with changes in sensory-motor measures (grip or pinch movements). These novel results suggest recovery of functional sensory activation as one possible mechanism underlying the effectiveness of intensive constraint-based therapy on motor functions in the more affected upper extremity in CP. However, maladaptive effects on the less affected constrained extremity may also have occurred. Our findings also highlight the use of electrical neuroimaging as feasible methodology to measure changes in tactile function after treatment even in young children, as it does not require active participation.
| S-EPMC6250030 | biostudies-other
Project description:ObjectivesThe aim of this study was to evaluate health problems, accommodation, and mobility of adult patients with cerebral palsy (CP).Patients and methodsBetween September 2018 and September 2019, a total of 70 adult CP patients (37 males, 33 females; mean age 29.4±10.2 years; range, 19 to 68 years) who were admitted to our clinic were included. Accommodation, education status, mental state, comorbidities, spasticity, contracture, deformity, and mobility of the patients were evaluated.ResultsOf the patients, 24.3% were diplegic, 21.4% were hemiplegic, 32.9% were tetraplegic, 15.7% were dyskinetic, and 5.7% had mixed form of CP. Among the patient, 38.6% had normal mental ability and 21.4% had severe mental retardation. A total of 92.9% of the patients were living with their family, 85.7% were unemployed, 10% were illiterate, and 21.4% had no health problems. Speech disorder was the most common health issue in 52.9% of the patients. Other health concerns included sensory problems, epilepsy, bladder/intestinal problems, nutritional problems, and respiratory and skin problems. The ratio of pain was 31.4%. Mild deformity was present in 54.3% of the patients, 43.7% were wheelchair-dependent, and 25.7% were Gross Motor Function Classification System (GMFCS) Level V.ConclusionRecognition and understanding health problems and living conditions of adult patients with CP would be useful both in determining the treatment goals of pediatric CP patients and in improving the quality of life of adult CP patients.
| S-EPMC7756828 | biostudies-literature
Project description:We have analysed a family with an autosomal recessive type of tetraplegic cerebral palsy with mental retardation, reduction of cerebral white matter, and atrophy of the cerebellum in an inbred sibship. Homozygosity mapping using SNPs was performed to identify the chromosomal locus for the disease. In the 14 Mb candidate region on chromosome 7q22, RNA expression profiling was used to select among the 203 genes in the area.
2009-12-11 | GSE16447 | GEO
Project description:This was a prospective, repeat-treatment, open-label study (NCT01251380) of abobotulinumtoxinA for the management of lower limb spasticity in children who had completed a double-blind study. Children (2-17 years) received injections into the gastrocnemius-soleus complex, and other distal and proximal muscles as required (maximum total dose per injection cycle: 30 U/kg or 1000U). A total of 216 of the 241 double-blind patients entered the extension study and 207 received ?1 open label injection into the gastrocnemius-soleus; 17-24% of patients also had injections into the hamstrings. The most frequent adverse events were related to common childhood infections and the most frequent treatment-related adverse event was injection site pain (n = 10). There was no evidence of a cumulative effect on adverse events. Sustained significant clinical improvements in muscle tone (Modified Ashworth Scale), spasticity (Tardieu Scale), overall clinical benefit (Physicians Global Assessment), and goal attainment (Goal Attainment Scale) were also observed across treatment cycles.
| S-EPMC5652649 | biostudies-literature
Project description:Cerebral palsy (CP) is a neurodevelopmental disorder that results in functional motor impairment and disability in children. CP is characterized by neural injury though many children do not exhibit brain lesions or damage. Advanced structural MRI measures may be more sensitively related to clinical outcomes in this population. Magnetic resonance elastography (MRE) measures the viscoelastic mechanical properties of brain tissue, which vary extensively between normal and disease states, and we hypothesized that the viscoelasticity of brain tissue is reduced in children with CP. Using a global region-of-interest-based analysis, we found that the stiffness of the cerebral gray matter in children with CP is significantly lower than in typically developing (TD) children, while the damping ratio of gray matter is significantly higher in CP. A voxel-wise analysis confirmed this finding, and additionally found stiffness and damping ratio differences between groups in regions of white matter. These results indicate that there is a difference in brain tissue health in children with CP that is quantifiable through stiffness and damping ratio measured with MRE. Understanding brain tissue mechanics in the pediatric CP population may aid in the diagnosis and evaluation of CP.
| S-EPMC6416970 | biostudies-literature