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

Université de Sherbrooke

Status and phase: Enrolling; Phase 4

Conditions: Nonepileptic, Stereotypical and Intermittent Symptoms; Cortical Depression; Cortical Depolarization; NESIS; Epilepsy; Seizure; Chronic Subdural Hematoma

Treatments: Drug: Levetiracetam; Drug: Topamax

Study type: Interventional

Funder types: Other

Identifiers

NCT04759196

MP-31-2021-3687

Details and patient eligibility

About

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).

Full 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.

Enrollment: 56 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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56 participants in 4 patient groups

NESIS - Levetiracetam

Active Comparator group

Description:

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.

Treatment:

Drug: Levetiracetam

NESIS - Topiramate

Experimental group

Description:

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.

Treatment:

Drug: Topamax

Non NESIS - Levetiracetam

Active Comparator group

Description:

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.

Treatment:

Drug: Levetiracetam

Non-NESIS - Topiramate

Experimental group

Description:

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.

Treatment:

Drug: Topamax