Minimally Invasive Surgical Epilepsy Trial for Temporal Lobe Epilepsy

Study Overview
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Brief Summary
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Temporal lobe epilepsy (TLE) is a chronically neurological disease characterized by progressive seizures. TLE is the most frequent subtype of refractory focal epilepsy in adults. Epilepsy surgery has proven to be very efficient in TLE and superior to medical therapy in two randomized controlled trials. According to the previous experience, the investigators use functional anterior temporal lobectomy (FATL) via minicraniotomy for TLE. To date, this minimally invasive open surgery has been not reported. The investigators here present a protocol of a prospective trail which for the first time evaluates the outcomes of this new surgical therapy for TLE.

Detailed Description
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Temporal lobe epilepsy (TLE) is a chronically neurological disease characterized by progressive seizures, followed by a latency period of several years after various injuries including febrile seizures, infection, trauma, tumors, and vascular malformation. Hippocampal sclerosis is the most common histopathological finding. The macroscopic changes of TLE with hippocampal sclerosis include the diminished size, sclerosis, and reduced metabolism in mesial temporal structures (amygdala, hippocampus, and parahippocampal gyrus). The microscopic changes include neuronal loss, gliosis, and axonal reorganization. As TLE progresses, most of patients become resistant to current antiepileptic drugs. Therefore, TLE is the most frequent subtype of refractory focal epilepsy in adults. Epilepsy surgery has proven to be very efficient for TLE and superior to medical therapy in two randomized controlled trials. Patients with surgical therapy have high seizure-free rate with the range of 60% to 80 % while less than 5% with medical treatment. Anterior temporal lobectomy (ATL) is the most frequently used approach for TLE. For patients with TLE, Engel suggested referral to ATL should be strongly considered. The decision analysis showed that ATL increased life expectancy and quality- adjusted life expectancy in patients with TLE compared with medical management. Nevertheless, ATL is performed by large frontotemporal craniotomy. Although complication rates after temporal lobectomy have decreased dramatically over time, ATL creates a large cavity with temporal lobe resected, causing potential complications such as bleeding, brain shifts and subdural collections. With the advances in minimally invasive surgery, surgical techniques of ATL for TLE need to be continuously improved. For this reason, the investigators modify the surgical approach. Functional anterior temporal lobectomy (FATL) via minicraniotomy is established. Recently, 25 patients with TLE undergoing FATL obtained satisfactory outcomes in our center (unpublished data). To date, this new open surgery for TLE has been not reported. The safety and efficacy of FATL need to be verified. Therefore, the investigators here present a protocol of the minimally invasive surgical epilepsy trial for TLE (MISET-TLE) which for the first time evaluates the outcomes of FATL as a new surgical approach for TLE.

Official Title
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Functional Anterior Temporal Lobectomy Via Minicraniotomy as a Novel Surgical Therapy for Temporal Lobe Epilepsy: a Randomized, Controlled Trial

Conditions
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Temporal Lobe Epilepsy, Open Surgery, Minimally Invasive Surgery

Intervention / Treatment
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* Procedure: Functional anterior temporal lobectomy (FATL)
* Procedure: Anterior temporal lobectomy (ATL)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male or female aged between 18 and 60 years; drug- resistant temporal lobe epilepsy, remaining seizures after two or more tolerated and appropriately chosen antiepileptic drugs; monthly or more seizures during the preceding year prior to trial; the full- scale intelligence quotient (IQ) more than 70, understanding and completing the trial; signing the informed consent; good compliance, at least 12- month follow- up after surgery. Exclusion Criteria: tumor in temporal lobe; extratemporal epilepsy and temporal plus epilepsy; drug- responsive epilepsy, seizure freedom with current drugs in recent one year; pseudoseizures; seizures arising from bilateral temporal lobes; significant comorbidities including progressive neurological disorders, active psychosis, and drug abuse; a full- scale IQ lower than 70, unable to complete tests; previous epilepsy surgery; poor compliance and inadequate follow- up.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: a single-center, prospective, single-blinded, double-arm, randomized, controlled trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Functional anterior temporal lobectomy (FATL)<br>FATL via minicraniotomy is a new surgical approach, consisting of amygdalohippocampectomy and the lateral temporal lobotomy. | Procedure: Functional anterior temporal lobectomy (FATL)<br>* Patients are placed in the supine position with the head contralaterally rotated 30°. The 3D model of incision and bone flap is printed prior to surgery by the slicer software based on the MRI data. Slightly curve incision with the length of about 6 cm in the temporal region is marked according to the 3D model. Temporal craniotomy via small bone window with the diameter of about 3 cm is performed. From the temporal pole along T1 about 5 cm posteriorly, temporal horn is opened by dissecting the middle temporal gyrus. The head of temporal horn is exposed. The amygdala is resected. Then, the parahippocampal gyrus and hippocampus are en bloc resected. The lateral temporal lobotomy is easy due to large view following the removal of mesial structures. The lateral posterior temporal lobotomy is no more than 5 cm from the temporal pole.<br>|
| Active Comparator: Anterior temporal lobectomy (ATL)<br>ATL via large frontotemporal craniotomy is a conventional surgical approach, consisting of amygdalohippocampectomy and en bloc resection of the lateral temporal lobe. | Procedure: Anterior temporal lobectomy (ATL)<br>* Patients are placed in the supine position with the head contralaterally rotated 30°. Large frontotemporal craniotomy is performed. Question mark-shaped incision with the length of 20- 25 cm in the frontotemporal region is marked. The size of the bone flap is approximately 5×7 cm for the exposure of lateral temporal lobe. ATL consists of en bloc resection of the anterior 5 cm of lateral temporal lobe, followed by the removal of mesial structures including the amygdala, parahippocampal gyrus, and hippocampus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Surgery duration | Surgery duration in hours, the time from the beginning of incising the skin to the finish of suturing the skin. | At the end of the surgery. | 
| Blood loss | Blood loss in millilitres during the operation. | At the end of the surgery. | 
| Skin incision | Length of skin incision in centimetres | At the end of the surgery. | 
| Bone flap | Size of bone flap in square centimeter | At the end of the surgery. | 
| Postoperative hospital stay | Postoperative hospital stay in days, the time from the first postoperative day to discharge date. | Up to 1 month after surgery. | 
| Complications | The incidence of postoperative complications | Up to 1 year after epilepsy surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seizure outcomes classified by the International League Against Epilepsy (ILAE) | Seizure outcomes are classified by the International League Against Epilepsy (ILAE). Specific seizure classifications: class 1, seizure-free; class 2, only auras, no other seizures; class 3, 1-3 seizure days per year with or without auras; class 4, ≥4 seizure days per year and ≥50% reduction in baseline numbers of seizure days, with or without auras; class 5, <50% reduction and ≤100% increase in baseline numbers of seizure days, with or without auras; class 6, >100% increase in baseline numbers of seizure days, with or without auras. Proportion of each class is calculated. | Up to 1 year after epilepsy surgery | 
| Seizure outcomes classified by the Engel | Seizure outcomes are also classified by the Engel classification: class 1, free from disabling seizures; class 2, rare disabling seizures (almost seizure free); class 3, worthwhile improvement; class 4, no worthwhile improvement. Proportion of each class is calculated. | Up to 1 year after epilepsy surgery | 
| Quality of life assessed by the Quality of Life in Epilepsy Inventory- 89 | Quality of life is evaluated by the epilepsy- specific Quality of Life in Epilepsy Inventory- 89 (QOLIE- 89). QOLIE-89 is one of the special inventories applied mostly to assess QOL in research protocols, especially in long-term prospective clinical investigations. QOLIE- 89 has 89 items, range of scores, 0 to 100, with higher scores indicating better QOL. | Up to 1 year after epilepsy surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Temporal lobe epilepsy, Anterior temporal lobectomy, Functional anterior temporal lobectomy, Randomized controlled trial, Minicraniotomy