The Role of Imaging in the Diagnosis, Management and Prognosis of Possible Non-convulsive Status Epilepticus

Study Overview
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Brief Summary
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The investigators propose a prospective study of 20 control subjects and 180 consecutive patients with possible non-convulsive status epilepticus (NCSE). The investigators will obtain three functional images of the brain: Fluorodeoxyglucose positron emission tomography (FDG-PET) Perfusion (and structural) magnetic resonance (MR) images Computed tomography (CT) perfusion. Brain hypermetabolism/hyperperfusion is a strong argument to confirm a diagnosis of non-convulsive status epilepticus. The aim is to determine which of the three functional imaging techniques is the most sensitive and easy to obtain in the detection of hypermetabolism/hyperperfusion. The investigators will determine which EEG patterns are associated with hypermetabolism/perfusion. The investigators will further study and describe the management with antiseizure medication and outcome of the group with possible non-convulsive status epilepticus WITH hypermetabolism/hyperperfusion versus the group with possible non-convulsive status epilpticus WITHOUT hypermetabolism/hyperperfusion. The investigators will make recommendations for an imaging protocol in possible NCSE for widespread use. The aim is to offer guidelines to incorporate imaging in the diagnosis, management and prognosis of NCSE in patients with the ictal-interictal continuum.

Official Title
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The Role of Cerebral Functional, Structural and Spectral Imaging in the Diagnosis, Management and Prognosis of Status Epilepticus: a Prospective Study in Patients With the Ictal-interictal Continuum

Conditions
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Status Epilepticus, Ictal-interictal Continuum, Positron-emission Tomography, Perfusion Weighted MRI, Perfusion CT

Intervention / Treatment
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* Diagnostic Test: MRI scan including arterial spin labelling of the brain
* Diagnostic Test: CT perfusion scan of the brain
* Diagnostic Test: FDG-PET scan of the brain


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - The patient has possible non-convulsive status epilepticus with scalp or invasive EEG with ictal-interictal continuum patterns on EEG Exclusion Criteria: The patient has a contra-indication for MRI such as metal implants The patient has contrast sensitivity The patiensuffers from claustrophobia or cannot tolerate confinement during PET-MRI scanning procedures

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Possible non-convulsive status epilepticus with ictal-interictal continuum EEG patterns<br>Patients with a possible non-convulsive status epilepticus, according to American Clinical Neurophysiology Criteria (ACNS) (2021). | Diagnostic Test: MRI scan including arterial spin labelling of the brain<br>* Arterial Spin Labelling sequence, T2-weighted FLAIR images and T1-weighted images and diffusion weighted imaging sequence will be recorded<br>* Other names: Brain perfusion;Diagnostic Test: CT perfusion scan of the brain<br>* Siemens Naeotom Alpha with quantum technology (photon-counting)<br>* Other names: Brain perfusion;Diagnostic Test: FDG-PET scan of the brain<br>* An FDG-PET scan will be acquired on a GE Signa 3T PET-MR scanner. FDG-PET images will be assessed for focal hypermetabolism, including semiquantitative analysis of the maximal standard uptake value (SUVmax) relative to the SUVmax of the pons (SUVr pons)<br>* Other names: Brain metabolism;|
| Other: Healthy control subjects<br>Healthy control subjects. | Diagnostic Test: MRI scan including arterial spin labelling of the brain<br>* Arterial Spin Labelling sequence, T2-weighted FLAIR images and T1-weighted images and diffusion weighted imaging sequence will be recorded<br>* Other names: Brain perfusion;Diagnostic Test: CT perfusion scan of the brain<br>* Siemens Naeotom Alpha with quantum technology (photon-counting)<br>* Other names: Brain perfusion;Diagnostic Test: FDG-PET scan of the brain<br>* An FDG-PET scan will be acquired on a GE Signa 3T PET-MR scanner. FDG-PET images will be assessed for focal hypermetabolism, including semiquantitative analysis of the maximal standard uptake value (SUVmax) relative to the SUVmax of the pons (SUVr pons)<br>* Other names: Brain metabolism;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of MRI arterial spin labelling, CT perfusion and FDG-PET of the brain to detect hyperperfusion/hypermetabolism in possible non-convulsive status epilepticus | The investigators will determine which diagnostic test (MRI, CT or FDG-PET) is most sensitive in detecting hyperperfusion/hypermetabolism in possible non-convulsive status epilepticus to confirm a diagnosis of non-convulsive status epilepticus | Day 1 | 
| Correlation between FREQUENCY of ictal-interictal EEG patterns within 30 minutes after FDG-PET injection and standardised uptake value on FDG-PET. | The investigators will assess the correlation between standardised uptake value of the cerebral hypermetabolic region and the frequency of ictal-interictal EEG patterns within 30 minutes after injection of FDG. The frequency of ictal-interictal EEG patterns will be scored semi-quantitatively based on the American Clinical Neurophysiology Criteria (ACNS) criteria (2021). | Day 1 | 
| Correlation between PREVALENCE of ictal-interictal EEG patterns on EEG within 30 minutes after FDG-PET injection and standardised uptake value on FDG-PET. | The investigators will assess the correlation between standardised uptake value of the cerebral hypermetabolic region and the prevalence of ictal-interictal EEG patterns within 30 minutes after injection of FDG. The prevalence of ictal-interictal EEG patterns will be scored semi-quantitatively based on the American Clinical Neurophysiology Criteria (ACNS) (2021) | Day 1 | 
| The seizure freedom of patients with hypermetabolism compared to those with hypometabolism within 24 hours after undergoing an FDG-PET scan. | The investigators will assess the seizure freedom of patients in the hypermetabolic vs hypometabolic group. Patients will receive video EEG-monitoring for 24 hours after FDG-PET. Seizures will be defined according to current American Clinical Neurophysiology Criteria (ACNS) (2021) based on electrographic and clinical data. Hypermetabolism/hypometabolism will be qualitatively scored by a trained nuclearist. | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between SHARPNESS of ictal-interictal EEG patterns on EEG within 30 minutes after FDG-PET injection and standardised uptake value on FDG-PET. | The investigators will assess the correlation between standardised uptake value of the cerebral hypermetabolic region and the sharpness of ictal-interictal EEG patterns within 30 minutes after injection of FDG. The sharpness of ictal-interictal EEG patterns will be scored semi-quantitatively based on the American Clinical Neurophysiology Criteria (ACNS) (2021) | Day 1 | 
| Correlation between AMPLITUDE of ictal-interictal EEG patterns within 30 minutes after FDG-PET injection and standardised uptake value on FDG-PET | The investigators will assess the correlation between standardised uptake value of the cerebral hypermetabolic region and the amplitude of ictal-interictal EEG patterns within 30 minutes after injection of FDG. The amplitude of ictal-interictal EEG patterns will be scored semi-quantitatively based on the American Clinical Neurophysiology Criteria (ACNS) (2021) | Day 1 | 
| Correlation between EVOLUTION of ictal-interictal EEG patterns on EEG within 30 minutes after FDG-PET injection and standardised uptake value on FDG-PET. | The investigators will assess the correlation between standardised uptake value of the cerebral hypermetabolic region and evolution of ictal-interictal EEG patterns within 30 minutes after injection of FDG (i.e. static, fluctuating or evolving). The presence of fluctuation and evolution of ictal-interictal EEG patterns will be scored based on the American Clinical Neurophysiology Criteria (ACNS) (2021) | Day 1 | 
| Functional imaging in possible non-convulsive status epilepticus and INTERICTAL BURDEN | The investigators will compare interictal burden, defined as a percentage of ictal-interictal EEG patterns during continuous EEG monitoring, in the group with possible non-convulsive status epilepticus WITH hypermetabolism/hyperperfusion versus the group with possible non-convulsive status epilepticus WITHOUT hypermetabolism/hyperperfusion | Day 7 | 
| Functional imaging in possible non-convulsive status epilepticus and ANTISEIZURE MEDICATION (ASM) | The investigators will document all changes in antiseizure medication and compare these in the group with possible non-convulsive status epilepticus WITH hypermetabolism/hyperperfusion versus the group with possible non-convulsive status epilepticus WITHOUT hypermetabolism/hyperperfusion | Day 30 | 
| Functional imaging in possible non-convulsive status epilepticus and OUTCOME | The investigators will compare modified rankin scale (mRS) (0: no symptoms, 1: no significant disability, 2: slight disability, 3: moderate disability, 4: moderately severe disability, 5: severe disability and 6: death) at 7 days in the group with possible non-convulsive status epilepticus WITH hypermetabolism/hyperperfusion versus the group with possible non-convulsive status epilepticus WITHOUT hypermetabolism/hyperperfusion | Day 7 | 
| Functional imaging in possible non-convulsive status epilepticus and OUTCOME | The investigators will compare modified rankin scale (mRS) (0: no symptoms, 1: no significant disability, 2: slight disability, 3: moderate disability, 4: moderately severe disability, 5: severe disability and 6: death) at 30 days in the group with possible non-convulsive status epilepticus WITH hypermetabolism/hyperperfusion versus the group with possible non-convulsive status epilepticus WITHOUT hypermetabolism/hyperperfusion | Day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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possible non-convulsive status epilepticus, ictal-interictal continuum, MRI, FDG-PET, CT perfusion, EEG