Toxicological Screening by GC-MS Among Children Admitted for a First Afebrile Seizure

Study Overview
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Brief Summary
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Before the age of 14 years, 1% of the paediatric population will develop a seizure. The only systematically required complementary examination is an electroencephalogram (EEG). Additional biological or radiological examinations depend on the circumstances, the past medical history of the patient and other associated symptoms or clinical signs. A seizure can be the first sign of acute intoxication and represents a severity criterion. Failure to detect the toxic cause of a seizure can lead to a delay in the access or administration of an antidote if applicable. This can lead to target organ toxicity due to the absence of specific treatment. In the current French guidelines for a first seizure, a toxicological analysis is recommended if there is a possibility of exposure to toxic medications or products. However, this screening is often missing, unless a witness suggests that the child may have been exposed to a toxin.The recognition of a paediatric toxidrome is low among paediatricians, paediatric neurologists or emergency physicians. This is due to a lack of knowledge in clinical toxicology and the screening for toxic aetiology is not frequently or irrelevantly prescribed. There is an increasing number of proconvulsive molecules on the market. These molecules are not targeted in classic toxic screening. As result, a toxic cause of a seizure may be missed unless specific screening is performed. For all these reasons, little is known about the prevalence of toxic causes after a first episode of non-febrile seizure and probably under estimated in the paediatric population, especially in young children. New technologies for toxic detection like chromatography combined with mass spectrometry allow wide screening on different matrix. Initially dedicated to forensic analysis, they are more widely accessible for the exploration of the patients. The CASTox study is based on this context. The first aim will be to evaluate the prevalence of a toxicological cause by a systematic blood and urine screening of children admitted to Toulouse paediatric emergency unit for a first afebrile seizure. Moreover, secondary aim will be to describe the effect of the systematic screening on the management of the children.

Detailed Description
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Before the age of 14 years, 1% of the paediatric population will develop a seizure. The only systematically required complementary examination is an electroencephalogram (EEG). Additional biological or radiological examinations depend on the circumstances, the past medical history of the patient and other associated symptoms or clinical signs. A seizure can be the first sign of acute intoxication and represents a severity criterion. Failure to detect the toxic cause of a seizure can lead to a delay in the access or administration of an antidote if applicable. This can lead to target organ toxicity due to the absence of specific treatment. In the current French guidelines for a first seizure, a toxicological analysis is recommended if there is a possibility of exposure to toxic medications or products. However, this screening is often missing, unless a witness suggests that the child may have been exposed to a toxin.The recognition of a paediatric toxidrome is low among paediatricians, paediatric neurologists or emergency physicians. Since the end of the 90s, the molecules usually incriminated with seizure onset after intoxication are: with a high risk (polycyclic antidepressant, theophylline, isoniazid); intermediate risk (fluoroquinolones, tramadol, lidocaine, lithium, anticonvulsive medications) and low risk (selective serotonin reuptake inhibitors). Among infants, the molecules are quite different mainly because of the unintentional or malicious aspect of the intoxication and are dominated by sympathomimetic agents, antihistamine drugs, anticholinergic molecules, antidepressants and muscle relaxants. New drugs have been associated with seizures in young intoxicated children like bupropion, tramadol and venlafaxine. These agents are not detected by usual toxic analysis. For each patient and after getting the signed consent form, a toxicological analysis will be performed on blood and urine samples to extensively screen for proconvulsive molecules (alcohols, polycyclic antidepressants, salicylates, anticonvulsive medications (carbamazepine, phenytoin, valproic acid), drugs (cocaine and its metabolites, amphetamines, methamphetamine (ecstasy), cannabis, buprenorphine, methadone, mephedrone, codeine, pholcodine, hydromorphone), benzodiazepines, caffeine, theophylline, lidocaine, isoniazid, mefenamic acid, tramadol, ephedrine). This analysis will be performed using classic approach (immunoenzymatic detection) and by chromatography (GC) associated to mass spectrometry (MS) (Laboratory of Toxicology, University Hospital of Toulouse) - The other clinical data, biological results or tests requested by the physician in charge will be reported from the computerized medical file of each patient. For each patient hospitalized, a follow-up visit will be scheduled during hospitalization in order to report management of the children.

Official Title
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Toxicological Screening by GC-MS Among Children Admitted for a First Afebrile Seizure (CASTox): a Pilot Study

Conditions
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Afebrile Seizure (Finding)

Intervention / Treatment
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* Other: Collection of blood and urine samples
* Other: Clinical examination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Being aged between 1 month and 15 years for boys and 1 month and 11 years for girls Any first episode of afebrile seizure, independent of duration, type (generalized or not) occurring in children without any previous neurological history and admitted to Toulouse level III paediatric emergency unit (University Children Hospital, Toulouse) Consent form signed by parents or legal guardian Exclusion Criteria: Patient transferred from another hospital Absence of consent form signed by parents or legal guardian Seizure in a febrile context at the moment of inclusion Known history of neurological disorders Any kind of diagnosed epilepsy Renal or hepatocellular insufficiency Recent head trauma Coagulation disorders (hemophilia, secondary or primary thrombopenia) Known exposure to toxic molecules

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 15 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: Screening
Intervention Model: Single Group Assignment
Interventional Model Description: Transverse prevalence study. For each child, a toxicological screening will be carried out on the blood and urine for the research of proconvulsive molecules by conventional technique on the one hand and by gas chromatography coupled with a mass spectrograph on the other hand.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Children with afebrile seizure<br>For each child, a toxicological screening will be carried out on the blood and urine for the research of proconvulsive molecules by conventional technique on the one hand and by gas chromatography coupled with a mass spectrograph on the other hand. Intervention : Collection of blood and urine samples, and Clinical examination | Other: Collection of blood and urine samples<br>* For each child, a toxicological screening will be carried out on the blood and urine for the research of proconvulsive molecules by conventional technique on the one hand and by gas chromatography coupled with a mass spectrograph on the other hand.<br>Other: Clinical examination<br>* The other clinical data, any other biological samples or additional examinations are done under the opinion of the clinician or the neuropediatrics.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of one or several toxic molecules. | Analyzed by systematic screening of a blood and urine sample. | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The delay of detection of a cause for a first afebrile seizure in paediatric patients. | It is the time between the admission to paediatric emergency unit and the detection of the first afebrile seizure's cause for paediatric patients | Day 1 | 
| The length of stay in Toulouse paediatric emergency unit or in hospitalization. |  | Day 1 | 
| number of tests performed in the search of an aetiology |  | Day 1 | 
| The number of tests performed in the search of an aetiology. |  | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chromatography, Afebrile seizure, Toxicological screening, Mass spectrometry, Children