Use of a Tonometer to Identify Epileptogenic Lesions During Pediatric Epilepsy Surgery

NCT04344626 | Withdrawn FDA Device

• 1 other identifier: 17-001668-AM-00005
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 2

Brief Summary

Refractory epilepsy, meaning epilepsy that no longer responds to medication, is a common neurosurgical indication in children. In such cases, surgery is the treatment of choice. Complete resection of affected brain tissue is associated with highest probability of seizure freedom. However, epileptogenic brain tissue is visually identical to normal brain tissue, complicating complete resection. Modern investigative methods are of limited use. An important subjective assessment during surgery is that affected brain tissue feels stiffer, however there is presently no way to determine this without committing to resecting the affected area. It is hypothesized that intra-operative use of a tonometer (Diaton) will identify abnormal brain tissue stiffness in affected brain relative to normal brain. This will help identify stiffer brain regions without having to resect them. The objective is to determine if intra-operative use of a tonometer to measure brain tissue stiffness will offer additional precision in identifying epileptogenic lesions. In participants with refractory epilepsy, various locations on the cerebral cortex will be identified using standard pre-operative investigations like magnetic resonance imagin (MRI) and positron emission tomography (PET). These are areas of presumed normal and abnormal brain where the tonometer will be used during surgery to measure brain tissue stiffness. Brain tissue stiffness measurements will then be compared with results of routine pre-operative and intra-operative tests. Such comparisons will help determine if and to what extent intra-operative brain tissue stiffness measurements correlate with other tests and help identify epileptogenic brain tissue. 24 participants have already undergone intra-operative brain tonometry. Results in these participants are encouraging: abnormally high brain tissue stiffness measurements have consistently been identified and significantly associated with abnormal brain tissue. If the tonometer adequately identifies epileptogenic brain tissue through brain tissue stiffness measurements, it is possible that resection of identified tissue could lead to better post-operative outcomes, lowering seizure recurrences and neurological deficits.

Conditions

Epilepsy; Focal Cortical Dysplasia; Tuberous Sclerosis; Hemimegalencephaly; Polymicrogyria; Rasmussen Encephalitis; Sturge-Weber Syndrome; Gliosis; Stroke; Tumor, Brain

Keywords

Pediatric; Epilepsy; Tonometer; Focal cortical dysplasia; Tuberous sclerosis; Polymicrogyria; Rasmussen encephalitis; Sturge-Weber syndrome; Gliosis; Stroke; Developmental brain tumor

Outcome Measures

Primary Outcomes (3)

• Brain tissue stiffness measurements in mmHg as assessed by intraoperative use of a digital tonometer on presumed normal cerebral cortex

  Brain tonometry is a novel diagnostic approach, therefore normal and abnormal brain tissue stiffness values are not known. Measurements will be taken on presumed normal cerebral cortex, based on results of preoperative evaluations (magnetic resonance imaging, electro-encephalography, positron emission tomography), to establish potential normal brain tissue stiffness values.

  Intraoperative

• Brain tissue stiffness measurements in mmHg as assessed by intraoperative use of a digital tonometer on presumed pathological cerebral cortex

  Brain tonometry is a novel diagnostic approach, therefore normal and abnormal brain tissue stiffness values are not known. Measurements will be taken on presumed pathological (ex.: focal cortical dysplasia, tuberous sclerosis complex) cerebral cortex, based on results of preoperative evaluations (magnetic resonance imaging, electro-encephalography, positron emission tomography), to establish potential pathological brain tissue stiffness values.

  Intraoperative

• Correlation between brain tissue stiffness measurements in mmHg as assessed by novel intraoperative use of a digital tonometer and results of standard perioperative evaluations, using a 3D model of each brain

  Precise stereotactic coordinates for each brain tissue stiffness measurement will be recorded in a neuronavigation software. This will allow aggregation of brain tissue stiffness measurements and results of routine preoperative (MRI, EEG, PET), as well as intra-operative tests (ECoG, histopathological analysis of resected brain tissue) on a 3D model of each patient's brain. With this method, each brain tissue stiffness measurement can be compared to presence or absence of an underlying lesion on MRI; to presence or absence of epileptogenic foci on EEG; to presence of iso- or hypometabolism on PET; to presence or absence of epileptogenic foci on ECoG; to pathological diagnosis and severity of cortical disorganization on histopathological analysis. This will give insight into how well brain tissue stiffness measurements correlate with, and potentially identify, structural and functional epileptic brain anomalies.

  Perioperative

Secondary Outcomes (2)

• Surgical complications as assessed clinically on standard postoperative follow-up through study completion, up to 36 months

  Through study completion, up to 36 months

• Seizure freedom as assessed clinically on standard postoperative follow-up through study completion, up to 36 months

  Through study completion, up to 36 months

Study Arms (1)

Brain tonometry

EXPERIMENTAL

Participants undergoing intra-operative brain tissue stiffness measurements using a digital tonometer. Evaluated brain tissue is both presumed normal and abnormal based on results of pre-operative evaluations.

Device: Intra-operative brain tonometry

Interventions

Intra-operative brain tonometry DEVICE

Once the brain is exposed during surgery, a sterilized digital tonometer will be used to obtain brain tissue stiffness measurements at various locations of the cortex established based on results of pre-operative work-up. Precise stereotactic coordinates for each measurement will be recorded in a neuronavigation software to facilitate comparisons with results of other tests.

Also known as: Intra-operative brain tissue stiffness measurements, Digital tonometer

Brain tonometry

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with epilepsy who candidates for surgical treatment as established by a multidisciplinary committee specialized in epilepsy.
• Participants undergoing resective surgery for epilepsy of dysplastic (examples: focal cortical dysplasia, tuberous sclerosis, hemimegalencephaly, polymicrogyria) or non-dysplastic etiology (examples: developmental tumors, gliosis, stroke, Rasmussen encephalitis, Sturge-Weber syndrome).

You may not qualify if:

• Lesion of interest located in a difficult to access region, such as paralimbic structures, insula, depth-of-sulci or inter-hemispheric.

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Université de Montréal: collaborator

Study Sites (2)

UCLA Mattel Children's Hospital

Los Angeles, California, 90095, United States

Location

Sainte-Justine University Hospital

Montreal, Quebec, H3T1C5, Canada

Location

Related Publications (16)

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MeSH Terms

Conditions

Epilepsy; Focal Cortical Dysplasia; Tuberous Sclerosis; Hemimegalencephaly; Polymicrogyria; Encephalitis; Sturge-Weber Syndrome; Gliosis; Stroke; Brain Neoplasms

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Megalencephaly; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Malformations of Cortical Development, Group III; Neuroinflammatory Diseases; Hemangioma; Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Angiomatosis; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site

Study Officials

• Aria Fallah, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: No masking. Participants as well as caregivers and investigators will all be aware that patients are undergoing intra-operative brain tonometry (single arm study).
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Aria Fallah, MD, MSc, FRCSC, FAANS, FAAP; Neurosurgery

Model Details: There are no possible controls for such a study. Post-mortem brain tissue undergoes irreversible biomechanical changes and no healthy patient undergoes comparable neurosurgical procedures. To overcome this issue, an experimental model involving intra- and inter-participant comparisons is used. A single group of participants will undergo brain tonometry and resulting brain tissue stiffness measurements will be compared in predicted normal and abnormal brain tissue (as identified by pre-operative work-up) in each participant and between participants.

Study Record Dates

• First Submitted: February 26, 2020
• First Posted: April 14, 2020
• Study Start: July 16, 2018
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2023
• Last Updated: October 10, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); CA (1)