Longitudinal Early Epilepsy Study (LEES)

This longitudinal study will focus on the cognitive and brain development of children with absence epilepsy. In addition, the investigators aim to identify prognostic factors for cognitive deterioration and/or poor seizure control in these children.

Study Overview

• Status: Unknown
• Conditions: Absence Epilepsy; Epilepsy, Absence
• Intervention / Treatment: Other: MRI; Other: 24h-EEG + video; Other: Neuropsychological tests

Detailed Description

The aim is to study the cognitive and brain development of children with absence epilepsy. In addition, this study aims to identify prognostic factors for cognitive deterioration and/or poor seizure control.

Objective:

1. To study the development of cognition in children with absence epilepsy and the functional brain organization over time.
2. To find prognostic factors in terms of clinical, 24h-video-EEG or/and MRI characteristics for cognitive deterioration and/or poor seizure control in patients with absence epilepsy.

Study design:

2 year prospective longitudinal, controlled, comparative, clinical, follow up.

Study population:

60 children with recently diagnosed (<2 years) absence epilepsy, aged 6 to 12 years. In addition, this study includes a control group of 15 age and gender matched healthy volunteers.

Main study parameters/endpoints:

Endpoints are the development of clinical parameters (semiology, 24h-video-EEG and seizure control), neuropsychological/behavioural outcomes, structural/functional MRI parameters, and educational performance.

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

• Study Contact: Name: Eric LA Fonseca Wald, MD; Phone Number: +31 (0)43 387 65 84; Email: LEES.studie.kinderneurologie@mumc.nl
• Study Contact Backup: Name: Sylvia Klinkenberg, MD, PHD; Phone Number: +31 (0)43 387 70 54; Email: s.klinkenberg@mumc.nl

Study Locations

• Netherlands
  • Limburg
    • Heeze, Limburg, Netherlands, 5591 VE
      • Recruiting
      • Kempenhaeghe
      • Contact: Mariette HJ Debeij-van Hall, MD, PHD; Phone Number: +31 (0)40 227 97 77; Email: debeij-vanhallm@kempenhaeghe.nl
    • Maastricht, Limburg, Netherlands, 6202 AZ
      • Recruiting
      • Maastricht University Medical Center
      • Contact: Sylvia Klinkenberg, MD, PHD; Phone Number: +31 (0)43 387 70 54; Email: s.klinkenberg@mumc.nl
      • Contact: Eric LA Fonseca Wald, MD; Phone Number: +31 (0)43 387 65 84; Email: eric.fonsecawald@mumc.nl
      • Principal Investigator: Johan SH Vles, MD, PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

1. Children aged 6-12 years of age primarily presenting with episodes of brief loss of consciousness (absences) in an otherwise normal child in the previous 2 years. With an EEG showing 3 Hz (2.5-4.5 Hz) generalized rhythmic spike-and-wave complexes with a discharge duration of at least 3 seconds on a present or former EEG.
2. Overall healthy children aged 6-12 years of age following a regular school without major problems.

Description

Inclusion Criteria:

1. Primarily presented with daily occurring episodes of brief loss of consciousness (absences) in an otherwise normal child in the previous 2 years.
2. An EEG showing 3 Hz (2.5-4.5 Hz) generalized rhythmic spike-and-wave complexes with a discharge duration of at least 3 seconds on a present or former EEG(58).
3. Early absence epilepsy , defined as a confirmed diagnosis or seizures within 2 years.
4. Aged 6-12 years

5. Permitted accompanying factors:

   • A few generalized tonic-clonic seizures (assessed individually according to International League Against Epilepsy [ILAE] statements;
   • Mild myoclonic eye(lid) movements
   • Co-morbidities: Attention deficiency/concentration disorders, autism, dyslexia and anxiety. These do not form exclusion criteria as this is frequently seen in children with absence seizures and it might be uncertain if the co-morbidity is a manifestation of the absence epilepsy.

Exclusion Criteria:

• A potential subject (both for the control and patient group) who meets any of the following criteria will be excluded from participation in this study:

  • A diagnosis according to ILAE criteria of the following epilepsy syndromes: Juvenile Absence Epilepsy; Eyelid myoclonia with absences; Dravet syndrome; Epilepsy with myoclonic-atonic seizures; Epilepsy with Myoclonic Absences; Lennox-Gastaut syndrome; Frontal Lobe Epilepsy or other focal epilepsy.
  • A confirmed diagnosis of epilepsy/seizures for more than 2 years (59).
  • Recent hospitalizations in the last months or a history which might limit participation in or completion of the study protocol.
  • Behavioural characteristics which might hamper the gathering of useful MRI data.
  • Intellectual disability or other diseases/causes that may underlie cognitive impairment (i.e. neurodegenerative diseases).
  • History of major head trauma or head/brain surgery.
  • MRI lesions on (previous) structural brain MRI- or CT-scans or symptomatic epilepsies (e.g. epilepsy related to tumours, vascular abnormalities, congenital dysgenesia).
  • MRI contra-indications: claustrophobia, anxiety for an MRI scan, or presence of metallic objects (e.g. prostheses, pacemakers, metal clips on blood vessels, metal parts in the eye). Dental braces are no exclusion criterion for absence patients.
  • Regularly using drugs of abuse (asked during screening session).
  • Parents or participants (aged≥12 years) not willing to provide informed consent.
  • Parents or participants (aged≥12 years) who do not want to get informed whenever structural abnormalities are found during imaging.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Absence epilepsy; Children aged 6-12 years of age primarily presenting with episodes of brief loss of consciousness (absences) in an otherwise normal child in the previous 2 years. With an EEG showing 3 Hz (2.5-4.5 Hz) generalized rhythmic spike-and-wave complexes with a discharge duration of at least 3 seconds on a present or former EEG.	Other: MRI; Other: 24h-EEG + video; Other: Neuropsychological tests
Controls; Overall healthy children aged 6-12 years of age following a regular school without major problems.	Other: MRI; Other: Neuropsychological tests

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change of multimodal MRI parameters on brain connectivity	Baseline; first year; second year
Change of cognition measured by a battery of neuropsychological tests	Baseline; first year; second year
Time in months since start of medication till seizure control is attained, as assessed by anamnesis and a confirmatory routine-EEG.	Within 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age in months at which seizures began (age of onset) assessed by interview at the baseline measurment		Baseline
Seizure semiology assessed by anamnesis and video-EEG	Seizure semiology will be re-assessed at the different time points	Baseline; first year; second year
Epileptiform activity assessed by a 24h-EEG	Epileptiform acitivty will be re-assessed at the different time points	Baseline; first year; second year

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: Epilepsiecentrum Kempenhaeghe
• Investigators: Study Director: Johan SH Vles, MD, PHD, Maastricht University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Anticipated): September 1, 2019
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: September 26, 2016
• First Submitted That Met QC Criteria: November 2, 2016
• First Posted (Estimate): November 3, 2016

Study Record Updates

• Last Update Posted (Actual): November 19, 2018
• Last Update Submitted That Met QC Criteria: November 16, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes; Epilepsy; Epilepsy, Absence
• Other Study ID Numbers: NL55455.068.15; 152055 (Other Identifier: Maastricht University Medical Centre+)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No