Cognitive Function and Glymphatic System in Children With Epilepsy

Study Overview
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Brief Summary
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Epilepsy, one of the most common neurological disorders in childhood, is a chronic brain disease characterised by neurobiological, psychological and cognitive effects. Brain-derived neurotrophic factor (BDNF), neuropeptide-Y (NPY) and neural growth factor (NGF) play a role in different pathological processes seen in epileptogenesis. Neuron-specific enolase (NSE), a quantitative indicator of brain damage, has been shown to exhibit elevated serum levels in individuals with epilepsy and this has been associated with cognitive function. In neurological diseases, glymphatic fluid transport facilitated by astrocytic end feet and their expression of aquaporin-4 water channels is impaired. Activation of astrocytes is associated with tumour necrosis factor-α (TNF-α). The glymphatic system is reported as a therapeutic modality that may prevent cognitive impairment by preventing toxic waste protein accumulation. In patients with weak respiratory muscle strength, inspiratory muscle training, one of the respiratory physiotherapy techniques, is used as a supportive treatment. Weakness in respiratory muscle strength has also been found in the epilepsy disease group in which the glymphatic system is affected. The study will include 40 children with epilepsy who meet the inclusion criteria and volunteer to participate in the study. Children with epilepsy will be divided into two groups as experimental group (n=20) and control group (n=20) using block randomisation method. The experimental group will receive Inspiratory Muscle Training (IMT) with the Threshold device for 30 minutes every day for 8 weeks following routine medication use. The control group will be followed only with routine drug use. Demographic information of all participants will be recorded. Respiratory function will be assessed with a portable spirometer device, respiratory muscle strength with a portable electronic mouth pressure measuring device, and cognitive performance with the Number Sequence Learning Test (NSLT). EEG results, which will be used as epilepsy diagnosis method, will be recorded from the hospital database. Biochemical analyses; serum levels of brain derived neurotrophic factor (BDNF), neuron specific enolase (NSE), tumour necrosis factor alpha (TNF-α), neuropeptide-Y (NPY) and neural growth factor (NGF) will be performed with ELISA kit set. The initial evaluations performed at baseline in both groups will be repeated after 8 weeks. This research project was planned to prevent seizure development and improve biochemical parameters and cognitive function in paediatric epilepsy patients with inspiratory muscle training.

Official Title
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The Effect of Respiratory Muscle Performance on Cognitive Functions in Children With Epilepsy: Monitoring With Glymphatic System Activation and Neuropeptides

Conditions
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Epilepsy, Cognitive Dysfunction, Seizure, Epileptic

Intervention / Treatment
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* Device: Threshold IMT
* Drug: Antiepileptic medication


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with absence and rolandic type epilepsy according to International League Against Epilepsy (ILAE) classification. No previous respiratory physiotherapy. Maximal Inspiratory Pressure (MIP) value was below the expected value according to age and gender. Co-operative. Exclusion Criteria: Diagnosed with respiratory system disease. Have kyphoscoliosis and/or advanced postural alignment problems that affect respiratory function. Have severe mental problems. Those who follow the ketogenic diet. Any neuromuscular disease. Children with severe cardiac involvement, pulmonary embolism, mesenteric or portal thrombosis. Children with a diagnosis of inflammatory disease or C-reactive protein (CRP) analysis above normal limits. History of orthopaedic surgery.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Children diagnosed with epilepsy will be divided into two groups as experimental group and control group using block randomisation method.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>It consists of 20 children diagnosed with epilepsy who will receive inspiratory muscle training following routine medication use. The experimental group will receive inspiratory muscle training with the Thershold device for 30 minutes every day for 8 weeks. | Device: Threshold IMT<br>* Threshold is used in respiratory muscle training in the form of resistance loading.<br>Drug: Antiepileptic medication<br>* They will continue their antiepileptic medication prescribed by their doctor.<br>|
| Active Comparator: Control Group<br>The control group consists of 20 children diagnosed with epilepsy who will only be followed up with routine medication. | Drug: Antiepileptic medication<br>* They will continue their antiepileptic medication prescribed by their doctor.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory Muscle Strength | It will be measured using a portable electronic mouth pressure measuring device (micro RPM brand). | It will be measured at baseline and at the end of the experiment (at the end of 8 weeks). | 
| Spirometer | Pulmonary function test will be performed using Cosmed Pony FX. | It will be measured at baseline and at the end of the experiment (at the end of 8 weeks). | 
| Brain-derived neurotrophic factor (BDNF) | Blood samples will be collected interictal and serum will be separated and stored. Analyses will be performed by ELISA. | It will be measured at baseline and at the end of the experiment (at the end of 8 weeks). | 
| Neuron specific enolase (NSE) | Blood samples will be collected interictal and serum will be separated and stored. Analyses will be performed by ELISA. | It will be measured at baseline and at the end of the experiment (at the end of 8 weeks). | 
| Tumour necrosis factor alpha (TNF-α) | Blood samples will be collected interictal and serum will be separated and stored. Analyses will be performed by ELISA. | It will be measured at baseline and at the end of the experiment (at the end of 8 weeks). | 
| Neuropeptide-Y (NPY) | Blood samples will be collected interictal and serum will be separated and stored. Analyses will be performed by ELISA. | It will be measured at baseline and at the end of the experiment (at the end of 8 weeks). | 
| Neural growth factor (NGF) | Blood samples will be collected interictal and serum will be separated and stored. Analyses will be performed by ELISA. | It will be measured at baseline and at the end of the experiment (at the end of 8 weeks). | 
| Number Sequence Learning Test (NDSLT) | Evaluates short-term memory and learning ability. In the test content, there are two separate sequences of 8 or 9 digits in which the digits from 1 to 9 are mixed according to the age and education level of the participant. The selected sequence is read to the subject in order and the subject is asked to remember and say the sequence in the correct order. | It will be measured at baseline and at the end of the experiment (at the end of 8 weeks). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brain Derived Neurotrophic Factor, Cognition, Epilepsy, Glymphatic System, Breathing Exercises