Clinical trial NCT04759196: Generating Evidence on NonEpileptic, Stereotypical and Intermittent Symptoms (NESIS) in Chronic Subdural Hematomas
Official title: Generating Evidence on NonEpileptic, Stereotypical and Intermittent Symptoms (NESIS) in Chronic Subdural Hematomas
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Subdural Hematoma
Epilepsy; Seizure
Cortical Depression; Cortical Depolarization
Nonepileptic, Stereotypical and Intermittent Symptoms
NESIS
Keywords: Transient neurological symptoms
Levetiracetam; keppra
Lamotrigine; lamictal
Lead sponsor: Université de Sherbrooke
Sponsor class: OTHER
First posted: 2021-02-18
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: Through study completion, an average of 3 years
Secondary outcomes:
measure: Between-group difference in the number of TNS reported at 6 month in all participants (all NESIS scores)
timeFrame: Through study completion, an average of 3 years
measure: Incidence of cortical spreading depression on electrocorticography in the first postoperative week of patients with preoperative TNS.
timeFrame: Through study completion, an average of 3 years
Other outcomes:
Locations:
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke
state: Quebec
Study officials:
affiliation: Université de Sherbrooke
name: Christian Iorio-Morin, MD
role: PRINCIPAL_INVESTIGATOR
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