Neoplasms

Symptoms and General Pathology

All Conditions

Rare Diseases

Neoplasm Metastasis

Glioma

Neoplastic Processes

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Central Nervous System Depressants

All Drugs and Chemicals

Anesthetics

Critical steps of brain mapping and tumor removal will be performed in awake patient

Brain mapping and tumor removal will be performed in asleep patient

Surgeon performs critical steps of tumor removal in awake patient and controls his/her motor functions by brain mapping and assessing of voluntary movements

Tumor resection in awake patient

Surgeon removes tumor in asleep patient and controls his/her motor functions by brain mapping

Tumor resection in asleep patient

Alexander Dmitriev, MD

Objective of the study is to determine whether resection of gliomas and metastases of motor areas using awake surgery can achieve rarer motor deterioration after operation than using general anesthesia.

Awake surgery is usually used for tumor resection located in language areas. But patient's awakening during removal of mass lesions from motor areas can give additional opportunities. Besides checking of muscle contractions and integrity of motor fibers a surgeon in awake patient can assess planning of movements, praxis, visual feedback and vestibular processing of motions. Preserving of voluntary movements can be an additional proof that cortical motor centers and corticospinal tract were not damaged. At the moment there are no published results of randomized trials showing advantage of awake surgery in removal of mass lesions from motor brain areas.

Objective of the study is to determine whether resection of gliomas and metastases of motor areas using awake surgery can achieve rarer motor deterioration after operation than using general anesthesia.

Participants of the study will be randomly operated using awake surgery or general anesthesia. In both groups intraoperative neuromonitoring will be used. Dynamics of motor functions will be assessed before and after surgery by blinded neurologists.

Dynamics of motor function before, within 10 days after surgery and in 3 months after surgery will be assessed by neurosurgeon blinded for the treatment arm

General Anesthesia Versus Awake Surgery in Resection of Gliomas and Metastases of Motor Areas

General Anesthesia Versus Awake Surgery in Resection of Gliomas and Metastases of Motor Areas: a Randomised, Controlled Trial

Motor function is assessed in Medical Research Council scale and is compared before and after surgery, deterioration of motor function means decline of 1 grade or more; level of consciousness is assessed in Glasgow Coma scale, it's severe disturbance means decline to 9 points or less

Early motor function is assessed in Medical Research Council scale and is compared before and after surgery

Late motor function is assessed in Medical Research Council scale and is compared before and in 3 months after surgery

Speech function is assessed in Hendrix scale (2017) and is compared before and after surgery, deterioration of speech function means decline of 1 grade or more; level of consciousness is assessed in Glasgow Coma scale, it's severe depressing means decline to 9 points or less

Early speech function is assessed in Hendrix scale (2017)

Assesses patients' possibilities to self-service in Karnofsky Performance Status scale

Extent of resection = (preoperative tumor volume - postoperative tumor volume) / preoperative tumor volume x 100

Absence of tumor tissue in postoperative magnetic resonance imaging

Duration of surgery from skin incision till last skin suture

Blood loss from skin incision till last skin suture

How long patient was treated in intensive care unit

How long patient was treated in the hospital from admission till discharge

Which cerebral complications arose after surgery

Which somatic disorders arose after surgery

Whether repeated hospital admissions were required due to postoperative complications

Late speech function is assessed in Hendrix scale (2017)

Assessment of patients' possibilities to self-service in Karnofsky Performance Status scale

Sklifosovsky Institute of Emergency Care

Principal Investigator

Nervous System Diseases

Epilepsy

The PANAXIUM microelectrode ( 4x2 cm, 6 micron-thick electrode comprising 128 electrodes (28 500 µm electrodes, 96 30 µm diameter microelectrodes organized as tetrodes and 4 reference electrodes) will be placed on the cortical surface and repositioned every 90 seconds to sample the entire exposed brain surface. During the cortical electrical stimulation mapping phase, the electrode will be left at the edge of the field to detect epileptic discharges induced by stimulation. After resection, a new recording of the residual cortical surface will be made to check for persistent electrical anomalies. In the last 10 patients, the Panaxium microECoG will be compared with a macro-electrode for clinical use.

PANAXIUM MicroECoG

Gilles Huberfeld, MD, PhD

Bertrand MATHON, PhD

Johan PALLUD, PhD

Gilles HUBERFELD, PhD

The goal of this clinical trial is to validate the safety and to assess the quality of the signals provided by newly developed micro ElectroCorticoGraphy electrodes, provided by the company Panaxium, based on conductive polymers (PEDOT:PSS) in patients suffering of gliomas during resection surgery performed in awake condition. The main questions it aims to answer are:

* Safety of PEDOT:PSS microECoGs by assessing the rate of serious adverse events associated with their use during glioma surgery.
* Quality of PEDOT:PSS microECoGs recordings, as compared with recordings with traditional macroelectrodes, assessed by signal-to-noise ratio, impedance, ability to detect ripples (100-250 Hz) and fast ripples (250-600 Hz), ability to record epileptic activity (spikes and equivalent) either spontaneously or following direct electrical stimulation (afterdischarges).
* Practicality of microelectrodes use as perceived by neurosurgeons.
* Exploratory objectives: ability to record multi-unit activity, correlation between microECoG activity and tumor infiltration - local oncometabolite concentrations, determination of epileptic seizure rate during electrode use.

Participants will be recorded during awake glioma surgery by the newly developed micro ElectroCorticoGraphy electrodes and by routine macroelectrodes, as standard of care during both mapping of cortical activities and electrical stimulations used to assess the functional mapping mandatory for tailored tumor resection.

Electroencephalography (EEG) is a widely-used tool for studying brain activity, developed in humans in the late 1920s. Its indications have evolved as brain imaging techniques have developed, but it remains extremely useful in the fields of epileptology, comas, brain death, post-anoxic, metabolic, toxic encephalopathies and encephalitis. Alongside scalp EEG, intracranial recordings have been developed to optimize the localization of epileptic activity, with a view to epilepsy surgery.

Two main categories of intracranial electrodes are currently in use.

1. StereoElectroEncephalopGraphy electrodes consist of a stylus with a string of cylindrical contacts along its length, implanted directly into the brain parenchyma.
2. ElectroCorticoGraphy (ECoG) electrodes, non-penetrating, organized in strips or grids of 4 to 64 electrodes, disc-shaped, 0.2 to 1 cm in diameter, 0.5 to 1 mm thick, used to collect cerebral activity at the cortical surface.

Among its indication, surgery is a favorable circumstance for using ECoG. During brain surgery, cortical exposure enables cortical EEG recording without additional invasiveness. Intraoperative ECoG is of particular interest in epilepsy surgery, recently reactivated by the discovery of better electrophysiological biomarkers. In glioma surgery, often performed under awake conditions, cortical recording helps to establish a functional cerebral map and to adapt the resection. Indeed, ECoG recordings can be performed during awake surgery, without any disturbance of neuronal activity by anesthesia, to map epileptic activity (using visual identification of spikes) and to look for seizures induced by electrical stimulation. The evolution of these recording techniques is moving towards the development of tools for automatic analysis and mapping of new biomarkers, more relevant but more difficult to record because they are more focal and characterized by amplitudes close to background noise, such as high-frequency oscillations. New types of cortical electrodes are being developed to improve the spatial resolution (better localization), temporal resolution (faster activity detection) and detection sensitivity (signal-to-noise ratio) of cortical electrical signals.

New electrodes have recently been developed, based on the use of conductive organic polymer coatings such as poly(3,4-ethylenedioxythiophene (PEDOT: PSS), to optimize the signal-to-noise ratio, organized in electrode arrays that are 100 times thinner (5 microns vs. 0.5 mm for standard electrodes), 250 times smaller (between 30 and 500 microns vs. 8 mm for standard electrodes) and with more electrodes (128 vs. 6 or 8 for standard electrodes). This type of electrode, known as microECoG, has been validated in animals and has already been used in human research for intraoperative cortical recordings. They enable us to improve the quality of the recorded signal and to go down to a new scale, at the level of the neuron. Moreover, the very low thickness of the electrodes improves their conformability to the cortex, making them much more tolerable and enabling extended recordings to be envisaged as part of future man/machine interfaces.

The French company Panaxium is developing microECoG electrodes. As part of a collaborative project, Panaxium have designed a 4x2 cm, 6 micron-thick electrode comprising 128 electrodes (28 500 µm electrodes, 96 30 µm diameter microelectrodes organized as tetrodes and 4 reference electrodes) for clinical use in humans. The aim of this study is to explore the safety and quality of signals collected by the Panaxium microECoG during awake surgery for brain gliomas. Recording will be carried out using a high-performance EEG system CE-marked for medical use in humans.

The electrode will be placed on the cortical surface and repositioned every 90 seconds to sample the entire exposed brain surface. During the cortical electrical stimulation mapping phase, the electrode will be left at the edge of the field to detect epileptic discharges induced by stimulation. After resection, a new recording of the residual cortical surface will be made to check for persistent electrical anomalies. The surgeries and recordings will be carried out in 3 centers by neurosurgeons with expertise in brain tumors and awake surgery: Hôpital Sainte-Anne/GHU Paris), Hôpital Pietié-Salpêtrière, Hopital Fondation Adolphe de Rostschild. In the last 10 patients, the Panaxium microECoG will be compared with a macro-electrode for clinical use.

The primary endpoint will be the incidence of Serious Adverse Events due to the use of Panaxium microelectrodes during surgery and the following four days: cortical lesion by the electrode, infection, bleeding, aseptic meningitis, neurological deficit due to the use of the electrode, death. Secondary evaluation criteria will be the quality of recordings enabled by the Panaxium microECoG (signal-to-noise ratio reflecting signal quality, electrode impedance during surgery reflecting technical quality, detection of fast ripple (100-250 Hz) and fast ripple (250-600 Hz) oscillations), only possible with high-performance recorders, ability to record spontaneous epileptic activity (spikes and equivalent) or direct post-electrical stimulation (post-discharges)) and practicality of use as perceived by neurosurgeons. Finally, as an exploratory study for future uses of these electrodes, we will investigate their ability to record multi-unit activity (action potentials from single neurons) and the correlation between recorded activity and tumor infiltration, as well as local oncometabolite concentration.

Glioma Intraoperative MicroElectroCorticoGraphy

ability to record multi-unit activity, correlation between microECoG activity and tumor infiltration - local oncometabolite concentrations, determination of epileptic seizure rate during electrode use

Assessment of the safety of PEDOT:PSS microECoGs use by assessing the rate of serious adverse events associated with their use during glioma surgery

Quality of PEDOT:PSS microECoGs recordings assessment by signal-to-noise ratio, impedance, ability to detect ripples (100-250 Hz) and fast ripples (250-600 Hz), ability to record epileptic activity (spikes and equivalent) either spontaneously or following direct electrical stimulation (afterdischarges)

Practicality of microelectrodes use as perceived by neurosurgeons.

PANAXIUM

Institut National de la Santé Et de la Recherche Médicale, France

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

A total of 120 patients with brain tumors will be divided into our two groups, divided as follows:

1. In the group Pre-Per, 20 patients will be included by localization of electrical stimulation (60 patients in total). A patient who would be stimulable in two different areas could be included in two different groups.
2. In the group Pre-End, the subjects will be distributed by localization of the brain tumor, by lobe. A total of 20 participants will be included per lobe, corresponding to the frontal, temporal or parietal lobes (as a reminder, a tumor in the occipital lobe is an exclusion criterion), for a total of 60 participants

A maximum of 120 healthy matched sex and age subjects with patients will also be included

In the task, participants will see an object approaching toward them. During its movement, the object disappears, and the participants have to press a button to indicate when they estimate the object to contact with them. The motion parameters of the ball will be varied. The pre and post-surgery phases will test the participants in a long duration version of the task, approximately 30 minutes. The per surgery phase will be made of a 5 minutes version of the task, and the participants will receive a direct cortical stimulation for 4 seconds, at an intensity of 1 to 10 milliampere (mA), in the premotor ventral area, or posterior parietal cortex or somesthetic associative areas.

Behavioral task

The patient is first anesthetized for opening the scalp and skull, then awake. During this waking phase, the surgeon passes a few quick and simple tests to the patient, visual (for example, line bisection), language (for example, repeating a list of words) etc. While doing this task, the neurosurgeon disrupts the functioning of certain brain regions by direct electrical stimulation of the cortex in order to identify the regions whose dysfunction will have an impact on the current task.

During the operation, the areas involved in the construction of the peri-personal space will be stimulated by direct electrical stimulation, for a duration of 4 seconds at an intensity of 1 to 10 mA. These areas are:

* Ventral premotor cortex (with the exception of the primary motor cortex controlling the dominant hand, so as not to interfere with the motor response of the patient)
* Posterior parietal cortex
* Associative somesthetic areas

Awake surgery

The Mini Mental State Evaluation, which generally assesses the cognitive state of an individual through his 6 subtests testing both working memory, episodic and semantic praxies as well as spatio-temporal orientation capacity.

Neurological assessment

The Wechsler Adult Intelligence Scale was selected for two of its subtests: The Subtest Codes checking the processing of information, visuo-constructive abilities but also attention. The subtest Cubes evaluates the capacities of visuospatial and constructive organizations as well as the referencing of the space in relation to the subject.

The State-Trait Anxiety Inventory, consisting of two self-administered questionnaires: Questionnaire A, measuring the state of anxiety of the person on the present moment and B measuring anxiety as a character trait of the person

The Verbal Fluences test, in its oral version. Categorial and lexical fluences make it possible to quickly realize a possible lack of the word of the person as well as disturbances of working memory or the capacity of inhibition.

The board of the Corsi cubes that evaluates the non-verbal visual-spatial working memory of the participants with a reminder location that tests the visuo-spatial notebook and a reminder to who tests the central administrator of the working memory.

The neurocognitive naming test was chosen to verify correct access to both semantic memory and lexicon, as well as to test the early visual process of image processing necessary for our task.

Benton lines are commonly used to determine possible deficits in the localization of isolated objects or judgment of line direction.

The patient will finally pass a depression assessment test, answering Beck's questionnaire.

Franck-Emmanuel ROUX, MD

Robin BAURES

Franck-Emmanuel Roux, MD

During a brain surgery targeted to remove a brain tumor, the neurosurgeon wakes up the patient to delimit the tumor area exactly, and identify the surrounding areas, to limit the surgery damages. The present project aims at testing the patient in this awake phase to determine the brain areas implied in time to contact (TTC) perception, a function that allows determining the arrival time of moving objects and used in many tasks of our daily life.

Time to contact (TTC) estimation is a major visual function that allows an observer determining the time a moving object will take to reach him. It is however striking to note that the different brain areas supporting this function are not clearly identified, in particular the contribution of non-visual areas that are engaged in the definition of a peri-personal space for the observer. This lack could be fulfilled during a brain surgery experiment. Indeed, in such a surgery, the patient is awakened, and the surgeon apply direct cortical stimulation to de-activate specific brain areas while testing different cognitive function. The failure to succeed in the task indicates that this area is engaged in the cognitive function. The present study therefore will test different brain areas to investigate their respective contribution in the TTC estimation function.

Three groups of participants will be tested, in pre and per surgery phases. After an initial pre-surgery phase, patients for which the tumor does not interfere with the TTC estimation anility will be enrolled in the Pré-Per group, and tested during the brain surgery. Patients for which the pre-test indicates that the TTC estimation is damaged by the tumor, will be tested in pre-surgery phase only, constituting the Pré-End group. Finally, a control group, paired with the patients, will be tested as well.

For the patients, all the testing phases will be achieved during their medical process. The awake surgery is now a well-established technique, currently and usually done at the University Hospital Toulouse, and the present test in the per surgery phase only lasts a couple of minutes, no more than 5 minutes. As such, there is no additional risk carried out in the project.

Brain Areas of Time-To-Contact Perception: an Awake Surgery Study

Localizing in the Brain the Areas of Time to Contact Perception During an Awake Surgery

Look at how the cognitive functions of perception of time before contact are attached to brain structures, their communication with other zones, their alteration due to brain tumors for patients with a brain tumor compared to control subjects. The treatment of the study being an awakened awakening as part of the routine care, there is no risk of serious adverse event.

Brain mapping will be done through neurological examinations which are questionnaires and a risk-free task. All the tasks and all the questionnaires described in the paragraph "arm and intervention" will make it possible to meet this outcome.

Look to see if brain areas other than those targeted for stimulation in awake surgery are stimulated and therefore play a role in estimating time to contact.The treatment of the study being an awakened awakening as part of the routine care, there is no risk of serious adverse event.

Other brain areas will be define through neurological examinations which are questionnaires and a risk-free task. All the tasks and the questionnaires described in the paragraph "arm and intervention" will make it possible to meet this outcome.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
General Anesthesia Versus Awake Surgery in Resection of Gliomas and Metastases of Motor Areas	NCT05485038	Gliomas Benign Glioma, Maligna... Metastases to B...	Tumor resection... Tumor resection...	18 Years - 69 Years	Sklifosovsky Institute of Emergency Care
Glioma Intraoperative MicroElectroCorticoGraphy	NCT06408428	Glioma Epilepsy	PANAXIUM MicroE...	18 Years -	Institut National de la Santé Et de la Recherche Médicale, France
Brain Areas of Time-To-Contact Perception: an Awake Surgery Study	NCT04128306	Brain Tumors	Behavioral task Awake surgery Neurological as... Neurological as... Neurological as... Neurological as... Neurological as... Neurological as... Neurological as... Neurological as...	18 Years - 70 Years	University Hospital, Toulouse
General Anesthesia Versus Awake Surgery in Resection of Gliomas and Metastases of Motor Areas	NCT05485038	Gliomas Benign Glioma, Maligna... Metastases to B...	Tumor resection... Tumor resection...	18 Years - 69 Years	Sklifosovsky Institute of Emergency Care
Glioma Intraoperative MicroElectroCorticoGraphy	NCT06408428	Glioma Epilepsy	PANAXIUM MicroE...	18 Years -	Institut National de la Santé Et de la Recherche Médicale, France
Brain Areas of Time-To-Contact Perception: an Awake Surgery Study	NCT04128306	Brain Tumors	Behavioral task Awake surgery Neurological as... Neurological as... Neurological as... Neurological as... Neurological as... Neurological as... Neurological as... Neurological as...	18 Years - 70 Years	University Hospital, Toulouse
General Anesthesia Versus Awake Surgery in Resection of Gliomas and Metastases of Motor Areas	NCT05485038	Gliomas Benign Glioma, Maligna... Metastases to B...	Tumor resection... Tumor resection...	18 Years - 69 Years	Sklifosovsky Institute of Emergency Care

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