GENESIS: Generating Evidence on NonEpileptic, Stereotypical and Intermittent Symptoms (NESIS) in Chronic Subdural Hematomas

Sponsor

Université de Sherbrooke (Other)

Overall Status

Recruiting

CT.gov ID

NCT04759196

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Some patients with chronic subdural hematomas and transient neurological symptoms do not respond to standard antiepileptic drugs. The investigators think that some of them could have cortical depression rather than epileptic discharges. After an intensive literature review, the investigators found out that some antiepileptic dugs (Lamotrigine, Topiramate) were found to be efficient to treat cortical depression in other conditions (migraine, subarachnoid hemorrhage). In contrast, some other drugs (Levetiracetam) were not proved to be efficient. Knowing that, the investigators want to compare the efficacy of Topiramate against Levetiracetam in two different groups, the NESIS group (based on a NESIS score of 4 or more - increased risk of cortical depression) versus a non-NESIS group (score of 3 or less - increased risk of epileptic discharges).

Condition or Disease	Intervention/Treatment	Phase
Chronic Subdural Hematoma Epilepsy; Seizure Cortical Depression; Cortical Depolarization Nonepileptic, Stereotypical and Intermittent Symptoms NESIS	Drug: Topamax Drug: Levetiracetam	Phase 4

Detailed Description

Patients presenting with transient neurological symptoms in the context of subdural hemorrhage may present a diagnostic challenge. Many of these patients end up with a probable diagnosis of epilepsy (or acute symptomatic seizures), despite a negative electroencephalogram. The investigators believe that the origin of these transient neurologic symptoms in a significant subpopulation of these patients may in fact be cortical depolarization, rather than epileptiform activity. Very specific characteristics have already been identified that differentiate these patients from those who ultimately have epilepsy. The NESIS entity (nonepileptic, stereotypical, and intermittent symptoms) has been proposed to represent this group of patients. A NESIS score was then designed to help distinguish patients with epileptiform activity (confirmed by EEG) from those likely to have cortical depolarization. In other diseases presenting cortical depolarizations, certain antiepileptic treatments (including Topiramate) have already been recognized as effective. The investigators therefore want to perform a prospective, multicenter, randomized-controlled study (Topiramate group and Levetiracetam group) to determine whether a significant difference in the response to treatment exists between Topiramate and Levetiracetam in the NESIS group compared to the non-NESIS group. In addition, in a few eligible patients, the investigators will implant an electrocorticography electrode to demonstrate the existence of cortical depolarizations.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

56 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients with chronic subdural hematomas, transient neurological symptoms with negative EEG will be divided in two groups based on their NESIS scores (up to 3 (increased risk of epileptic seizures) and 4 or more (increased risk of cortical depression)). Those two groups are going to receive both Levetiracetam or Lamotrigine.Patients with chronic subdural hematomas, transient neurological symptoms with negative EEG will be divided in two groups based on their NESIS scores (up to 3 (increased risk of epileptic seizures) and 4 or more (increased risk of cortical depression)). Those two groups are going to receive both Levetiracetam or Lamotrigine.

Masking:

Double (Care Provider, Outcomes Assessor)

Masking Description:

The participant will not know the medication they are taking. When accepting to participate, they are going to have the full list of possible side effects, without knowing which one are link to which medication. The doctors in charge of administering the questionnaires will be blind. The person in charge of analyzing the results will also be blind.

Primary Purpose:

Treatment

Official Title:

Generating Evidence on NonEpileptic, Stereotypical and Intermittent Symptoms (NESIS) in Chronic Subdural Hematomas

Actual Study Start Date :

Mar 1, 2021

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: NESIS - Levetiracetam Participant with a score NESIS of 4 or more (increased risk of having cortical depression). Levetiracetam is an anti-epileptic drug known to be inefficient in other condition with cortical depression. It will be use as an active comparator.	Drug: Levetiracetam LEV : 500 mg BID, with increase of 1000 mg die divided in two doses each week until efficacy, to a maximum of 1500 mg BID. Other Names: LEV Keppra
Experimental: NESIS - Topiramate Participant with a score NESIS of 4 or more (increased risk of having cortical depression). Topiramate is an anti-epileptic drug known to be efficient in other condition with cortical depression. The investigators want to test his efficacy in chronic subdural hematoma with probable cortical depression.	Drug: Topamax TPM : 50 mg BID, with increased of 50 mg by week until efficacy, to a maximum of 100 mg BID. Other Names: Topiramate TPM
Active Comparator: Non NESIS - Levetiracetam Participant with a score NESIS of 3 or less (increased risk of having epileptic discharges). Levetiracetam is an anti-epileptic drug known to be inefficient in other condition with cortical depression. It will be use as an active comparator. Levetiracetam should be as efficient as Topiramate in a group a participant with epileptic discharges.	Drug: Levetiracetam LEV : 500 mg BID, with increase of 1000 mg die divided in two doses each week until efficacy, to a maximum of 1500 mg BID. Other Names: LEV Keppra
Experimental: Non-NESIS - Topiramate Participant with a score NESIS of 3 or less (increased risk of having epileptic discharges). Topiramate is an anti-epileptic drug known to be efficient in other condition with cortical depression. The investigators want to test his efficacy in chronic subdural hematoma with probable cortical depression. Topiramate should be as efficient as Levetiracetam in a group a participant with epileptic discharges.	Drug: Topamax TPM : 50 mg BID, with increased of 50 mg by week until efficacy, to a maximum of 100 mg BID. Other Names: Topiramate TPM

Outcome Measures

Primary Outcome Measures

Between-group difference in the number of TNS reported at 6 month in participants with a positive Nonepileptic, Stereotyped, Intermittent Symptoms (NESIS) score (4 and more) [Through study completion, an average of 3 years]
The aim of this study is to demonstrate the efficacy of Topiramate in the treatment of patients with transient neurological symptoms in the context of chronic subdural hemorrhage with a positive NESIS score (4 and more), in whom usual epilepsy treatment appears to be less effective. To do this, the effect of Topiramate (shown to be effective in cortical depressions) will be compared with that of Levetiracetam (which has not been shown to be effective in cortical depressions). This is going to be done by a questionnaire that will assess the resolution of symptoms or not, or the percentage of diminution.

Secondary Outcome Measures

Between-group difference in the number of TNS reported at 6 month in all participants (all NESIS scores) [Through study completion, an average of 3 years]
If the investigators manage to demonstrate a significant difference between the response to TPM and LEV in the NESIS group compared to the non-NESIS group with our questionnaire, the evidence concerning the existence of a different process at the origin of the NESIS group will then be more numerous. As demonstrated in studies on rats, cortical spreading depolarization respond well to TPM and not to LEV. Cortical depolarizations will then be the main hypothesis of the reason why some responds better to TPM than LEV in our study.
Incidence of cortical spreading depression on electrocorticography in the first postoperative week of patients with preoperative TNS. [Through study completion, an average of 3 years]
The investigators think that cortical depression rather then epileptic discharges could be involved in some patients with transient neurological symptoms in context of subdural hematomas. Some participant could need decompression surgery for their subdural hematoma. The investigators will offer the insertion of electrocorticography electrods while this surgery. The aim of this intervention will be to prove cortical depression in some subjects by using electrocorticography that will be read by a neurologist specialized in epilepsy.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Be aged ≥ 18 years
Chronic subdural hematoma
Transient neurological symptoms (Sensory, motor, cerebellar or speech symptoms, lasting 6 hours or less)
Initial negative EEG

Exclusion Criteria:

Contraindications to Levetiracetam
Psychiatric history (major depression, psychosis, risk of suicide)
History of hypersensitivity to LEV (anaphylaxis, angioedema, skin reaction)
Contraindications to Topiramate
History of hypersensitivity to TPM
Glaucoma
Past of nephrolithiasis
Known epilepsy or past seizure before the current subdural hemorrhage
Actual taking of an antiepileptic drug
Intracranial pathology not caused by subdural hematoma (intra-parenchymal hemorrhage, neoplasia)
Pregnancy or planning to
Inability to carry out the necessary follow-ups for the study
Refusal of the attending physician