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

Chronic Subdural Hematoma Clinical Trial

— GENESIS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04759196
• Other study ID #: MP-31-2021-3687
• Status: Recruiting
• Phase: Phase 4
• Start date: March 1, 2021
• Est. completion date: December 2024

Study information

• Verified date: April 2021
• Source: Université de Sherbrooke
• Contact: suzie adam, MD
• Phone: 5146990518
• Email: suzie.adam[@]usherbrooke.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 56
• Est. completion date: December 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Topamax
TPM : 50 mg BID, with increased of 50 mg by week until efficacy, to a maximum of 100 mg BID.
• 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.

Locations

Country	Name	City	State
Canada	Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Université de Sherbrooke

Country where clinical trial is conducted

Canada, 

References & Publications (26)

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Levesque M, Iorio-Morin C, Bocti C, Vézina C, Deacon C. Nonepileptic, Stereotypical, and Intermittent Symptoms (NESIS) in Patients With Subdural Hematoma: Proposal for a New Clinical Entity With Therapeutic and Prognostic Implications. Neurosurgery. 2020 Jul 1;87(1):96-103. doi: 10.1093/neuros/nyz355. — View Citation

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Toi H, Kinoshita K, Hirai S, Takai H, Hara K, Matsushita N, Matsubara S, Otani M, Muramatsu K, Matsuda S, Fushimi K, Uno M. Present epidemiology of chronic subdural hematoma in Japan: analysis of 63,358 cases recorded in a national administrative database. J Neurosurg. 2018 Jan;128(1):222-228. doi: 10.3171/2016.9.JNS16623. Epub 2017 Feb 3. — View Citation

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* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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.	Through study completion, an average of 3 years
Secondary	Between-group difference in the number of TNS reported at 6 month in all participants (all NESIS scores)	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.	Through study completion, an average of 3 years
Secondary	Incidence of cortical spreading depression on electrocorticography in the first postoperative week of patients with preoperative TNS.	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.	Through study completion, an average of 3 years

External Links

•   Levetiracetam. Drug information.
•   Santé canada, registres des produits pharmaceutiques. (Canadian drugs register)
•   Side effects classification
•   Topiramate. Drug information.