The purpose of this trial is to compare the effectiveness of early surgical intervention for mesial temporal lobe epilepsy to continued treatment with antiepileptic drugs.

Condition	Treatment or Intervention	Phase
Epilepsy Epilepsy, Temporal Lobe Seizures	Procedure: anteromesial temporal resection  Drug: antiepileptic drugs	Phase III

Further Study Details: 

Expected Total Enrollment:  200

Mesial temporal lobe epilepsy (MTLE) is the most common form of epilepsy, and the most medically intractable. An estimated one-quarter to one-half of the 400,000 patients in the United States with intractable epilepsy have MTLE. Generally, MTLE becomes intractable in adolescence and early adulthood. Persistence of seizures during this time commonly causes adverse social and psychological consequences which can become irreversible.

The current treatment of MTLE primarily consists of medications to control seizures. Usually surgical treatment is considered only if medications are not effective. Recent studies have shown that surgery can stop disabling seizures in 60 to 70% of patients with long standing MTLE. However, to date, no research study has examined surgery performed as an early therapy.

The goal of the study is to determine if more patients treated with early surgery become seizure free and have improved quality of life compared to similar patients who continue to receive antiepileptic medication only. This study will determine the difference in seizure frequency between the two groups and the impact of the two treatments on the quality of life of the participants.

Ages Eligible for Study:  12 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion criteria:

• Intractability: Two AEDs, one of which was either Dilantin, Tegretol, Carbatrol, or Trileptal used in appropriate doses, have failed due to inefficacy, not intolerance.
• Frequency and Duration: Persistence of disabling seizures at 6 per year or greater for less than two years after onset, or after recurrence if initial treatment resulted in seizure freedom for 6 or more months.
• Age: 12 years or older at baseline visit.
• History: Simple and complex partial seizures, with or without secondarily generalized seizures beginning in childhood or later, with or without febrile convulsions earlier.
• Absence of a history of serious cerebral insult after the age of 5; a progressive neurological disorder; mental retardation (I.Q. less than 70); psychogenic seizures; focal neurological deficits other than memory disturbances; unequivocal focal extratemporal EEG slowing or interictal spikes; or lesions on neuroimaging outside of the mesial temporal area.
• Seizure semiology: Auras that occur in isolation and are not primary sensory other than olfactory or gustatory. Absence of initial focal motor movements other than automatisms or dystonic posturing. Presence of postictal confusion.
• Neurological examination: No unexplained focal or lateralized neurological deficits other than memory dysfunction.
• Baseline QOL and ancillary outcome data: - Adolescents - QOLIE-48-AD, CHQ, CBCL, PANAS, Life Events Scale, FAC, FEICS-PC completed. - Adults - QOLIE-82/ESI55, locus of control, PANAS, Life Events Scale, FAD, FEICS-PC completed. - Global rating scale completed. - Baseline ancillary outcomes completed. Psychiatric evaluation: No evidence of psychosis, current or recent substance abuse, suicidality, anorexia, or psychogenic seizures. Baseline BSI and MINI or KSADS completed.
• Neuropsychological testing: I.Q. of greater than 70. No significant focal neurocognitive dysfunction inconsistent with MRI and PET findings. Baseline neuropsychological testing completed.
• Neuroimaging: Hippocampal atrophy on MRI T1 imaging with either increased ipsilateral mesial signal on T2 imaging, or ipsilateral hypometabolism on PET (Class I), or either hippocampal atrophy on MRI only, or temporal hypometabolism on PET only (Class II). - Absence of temporal neocortical or extratemporal lesions on MRI, or diffuse unilateral or bilateral hypometabolism on PET.
• Video-EEG Monitoring: - If neuroimaging is Class I, ictal EEG onset is lateralized to the ipsilateral side; if neuroimaging is Class II, ictal EEG onset is focal on the ipsilateral side. - Absence of contralateral or extratemporal ictal onset. - Absence of persistent extratemporal, or predominant contralateral focal interictal spikes or slowing, or generalized interictal spikes. - Absence of psychogenic seizures.
• Seizure baseline: Seizure log, seizure report forms, and seizure severity scale completed.
• IAP: In those randomized to surgery only, contralateral hemisphere can support memory.

Jerome Engel, Jr., M.D., Ph.D.      310-825-5745    engel@ucla.edu

Arizona
      Barrow Neurological Institute, Phoenix,  Arizona,  85013,  United States; Recruiting
California
      Stanford University Medical Center, Stanford,  California,  94305-5235,  United States; Recruiting
      UCLA School of Medicine, Department of Neurology, Los Angeles,  California,  90095-1769,  United States; Recruiting
Florida
      Bayfront Medical Center, St. Petersburg,  Florida,  33701,  United States; Recruiting
Georgia
      Emory University, Atlanta,  Georgia,  30322,  United States; Recruiting
Illinois
      Northwestern University, Chicago,  Illinois,  60611,  United States; Recruiting
Maryland
      Johns Hopkins University, Baltimore,  Maryland,  21287,  United States; Recruiting
Massachusetts
      Massachusetts General Hospital, Boston,  Massachusetts,  02114,  United States; Recruiting
Michigan
      University of Michigan, Department of Neurology, Ann Arbor,  Michigan,  48109-0036,  United States; Recruiting
Minnesota
      MINCEP Epilepsy Care, Minneapolis,  Minnesota,  55416,  United States; Recruiting
Missouri
      Washington Unviersity, St. Louis,  Missouri,  63110,  United States; Recruiting
New Mexico
      University of New Mexico, Albuquerque,  New Mexico,  97131,  United States; Recruiting
New York
      Columbia University, New York,  New York,  10032,  United States; Recruiting
      University of Rochester, Department of Neurology, Rochester,  New York,  14642,  United States; Recruiting
Ohio
      Cleveland Clinic, Cleveland,  Ohio,  44195,  United States; Recruiting
Pennsylvania
      Thomas Jefferson University Hospital, Philadelphia,  Pennsylvania,  19107,  United States; Recruiting
Tennessee
      Vanderbilt University, Nashville,  Tennessee,  37212,  United States; Recruiting
Texas
      UT Southwestern Medical Center, Department of Neurology, Dallas,  Texas,  75390-9036,  United States; Recruiting
Washington
      Swedish Medical Center, Seattle,  Washington,  98122,  United States; Recruiting

Study chairs or principal investigators

Jerome Engel, Jr., M.D., Ph.D.,  Principal Investigator,  UCLA School of Medicine, Department of Neurology   

Study ID Numbers:  R01NS42372
Record last reviewed:  November 2004
Last Updated:  November 15, 2004
Record first received:  June 24, 2002
ClinicalTrials.gov Identifier:  NCT00040326
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08