Condition category
Nervous System Diseases
Date applied
11/08/2008
Date assigned
21/08/2008
Last edited
28/08/2008
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.meb.uni-bonn.de/epileptologie/sfb-tr3/

Contact information

Type

Scientific

Primary contact

Prof Johannes Schramm

ORCID ID

Contact details

Sigmund-Freud-Str. 25
Bonn
53105
Germany

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Prospective and randomised multicentre trial investigating the pros and cons of different extent of mesial resection in surgery for mesial temporal lobe epilepsy

Acronym

Study hypothesis

There is an ongoing debate about the mesial resection extent in the surgical treatment of temporal lobe (TL) epilepsy patients and its relation to seizure freedom and neuropsychological outcome. Surgical resection strategies developed from larger resections removing up to 2/3 of the temporal lobe to more selective and smaller resection types.

The objective of this study is to assess the significance of the extent of resection of mesial structures (hippocampus and parahippocampus) to achieve seizure freedom after surgery for temporal lobe epilepsy.

The main goals of this project are to test two hypotheses:
1. Smaller TL resections are associated with less neuropsychological deterioration
2. Post-operative seizure freedom is comparably good in smaller mesial resection

Ethics approval

Ethics approval received from the Ethics Committee of the University of Bonn Medical Centre on the 2nd February 2001 (ref: 237/00)

Study design

Prospective, interventional, randomised multicentre study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Patient information can be found at:
http://www.ukb.intern/42256BC8002AF3E7/vwWebPagesByID/8BE510569EF540CCC12571D40056E8CD

Condition

Intractable mesial temporal lobe epilepsy (MTLE)

Intervention

As part of the presurgical evaluation patients underwent neuropsychological testing and MRI scanning. Healthy volunteers also underwent neuropsychological testing to serve as a control group regarding the cognitive abilities of the patients.

Patients were randomised to either a short (2.5 cm of hippocampal resection) or a long (3.5 resection length) resection group. The length of resection was to be determined intra-operatively after the opening of the temporal horn by using millimetre paper from the anterior tip of the temporal horn backwards placed on the hippocampal head along its length axis. Furthermore, manual volumetry of structural MRI datasets was used to evaluate the intended resection length.

Post-operatively, patients are seen for MRI-scanning, neuropsychological testing and medical consultation 3, 6 and 12 months after surgery.

Intervention type

Other

Phase

Not Specified

Drug names

Primary outcome measures

Seizure freedom at one year after surgery: defined as class I in the Engel Outcome Scale. The Engel Outcome Scale is administered post-operatively and determines the improvement/worsening after surgical intervention as follows:
1. Engel class I: seizure-free
2. Engel class II: almost seizure-free
3. Engel class III: significant seizure reduction
4. Engel class IV: no significant improvement

Patients belonging to Engel class I are termed as seizure free, the remaining patients (Engel II - IV) as non-seizure free patients in the present study.

Secondary analysis:
Seizure freeness in subgroups (based on neuropathological analyses), e.g. patients with mesial temporal sclerosis.

Secondary outcome measures

Neuropsychological testing:
Each patient underwent comprehensive neuropsychological testing pre-operatively and 12-months post-operatively. For the comprehensive purpose of this study, various neuropsychological parameters are aggregated, resulting in scores for seven major cognitive domains:
1. Verbal learning and memory: two parallel versions of a pre- and post-operative verbal learning test (Verbaler Lern- und Merkfähigkeitstest [VLMT]). The VLMT (German adaptation of the Rey Auditory Verbal Learning Test) requires five trials of learning and recall of a word list consisting of 15 words, free recall immediately after distraction (learning/recall of a second list in one trial) and a recall after a half-hour delay, which is followed by a recognition trial (list with original words plus distractors).
2. Figural learning and memory was obtained using the DCS-R, a German revised version of the DCS, a design list learning test (Diagnostikum für Zerebralschädigung)
3. Language functions:
3.1. Confrontation naming, Boston Naming Test
3.2. Phonematic and semantic fluency
3.3. Token Test, a subtest of the Aachener Aphasie-Test (a german test battery for aphasia) which is seen to measure verbal comprehension
4. Attention functions:
4.1. D2-Test, a letter cancellation test
4.2. The c.I.T., a short test to measure cerebral insufficiency (Kurztest für cerebrale Insuffizienz)
5. Psychomotor speed, mental tracking and cognitive flexibility:
5.1. Trail Making Test A and B (TMT-A/B)
5.2. Motoric sequences after Lurija
5.3. Purdue Pegboard
5.4. Finger Tapping Test
6. Visual and spatial abilities:
6.1. Subtest LPS-7 of the Leistungsprüfsystem (LPS), a german intelligence battery
6.2. The Mosaic-Test, a subtest of the German version of the Wechsler Adult Intelligence Scale-Revised (HAWIE-R)
6.3. Labyrinth test
7. Behaviour and personality features:
7.1. German version of the Beck Depression Inventory (BDI)
7.2. FPZ (Fragebogen zur Persönlichkeit bei zerebralen Erkrankungen), an unpublished German CNS-disease related personality questionnaire
7.3. Quality of Life Inventory in Epilepsy, 10-item version (QOLI-10)

All neuropsychological results were classified into five categories (0 = noticeably abnormal, 1 = moderately abnormal, 2 = borderline, 3 = without pathological findings, 4 = above average).

Overall trial start date

15/10/2002

Overall trial end date

30/06/2008

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients suffering from intractable temporal lobe epilepsy
2. Drug resistance: seizure history lasting more than two years
3. Pre-surgical evaluation led to the recommendation of either a partial temporal lobe resection combined with amygdalohippocampectomy or a more restricted selected selective amygdalohippocampectomy (SAH)
4. Only cases with mesial involvement were included
5. Patients had to be at least 18 years old (either sex) and able to understand the study plan
6. Written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

200 to 250

Participant exclusion criteria

1. Previous temporal lobe surgery
2. Inability to do undergo neuropsychological testing because of retardation or foreign language
3. Mesial resection restricted to uncus and amygdala
4. No usable pre-operative magnetic resonance imaging (MRI) for volumetrical analyses
5. Pathology not allowing for randomisation (far dorsal reaching resection necessary)

Recruitment start date

15/10/2002

Recruitment end date

30/06/2008

Locations

Countries of recruitment

Germany

Trial participating centre

Sigmund-Freud-Str. 25
Bonn
53105
Germany

Sponsor information

Organisation

German Research Council (Deutsche Forschungsgemeinschaft [DFG]) (Germany)

Sponsor details

Kennedyallee 40
Bonn
53175
Germany

Sponsor type

Research council

Website

http://www.dfg.de/

Funders

Funder type

Research council

Funder name

German Research Council (Deutsche Forschungsgemeinschaft [DFG]) (Germany)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. Prospective study results (2008): http://www.ncbi.nlm.nih.gov/pubmed/18425622
2. Cognitive rehabilitation results (2008): http://www.ncbi.nlm.nih.gov/pubmed/18155965
3. Review (2008): http://www.ncbi.nlm.nih.gov/pubmed/18410360
4. Comment (2008): http://www.ncbi.nlm.nih.gov/pubmed/17955042
5. Memory and non-memory function results (2008): http://www.ncbi.nlm.nih.gov/pubmed/17941848
6. Research (2007): http://www.ncbi.nlm.nih.gov/pubmed/17728360
7. MRI volumetry results (2007): http://www.ncbi.nlm.nih.gov/pubmed/17131114
8. Children and aduly comparative study results (2005): http://www.ncbi.nlm.nih.gov/pubmed/16014650
9. One year follow-up results (2004): http://www.ncbi.nlm.nih.gov/pubmed/15270763
10. Cortical damage results (2004): http://www.ncbi.nlm.nih.gov/pubmed/14742620
11. Neuropsychological outcome results (2004): http://www.ncbi.nlm.nih.gov/pubmed/15230706

Publication citations

  1. Scorzin JE, König R, Müller CA, Fimmers R, Urbach H, Lehmann TN, Zentner J, Schramm J, Comparison of two different measurement techniques of hippocampal resection length in temporal lobe epilepsy: results of a prospective study., Acta Neurochir (Wien), 2008, 150, 8, 785-95; discussion 795, doi: 10.1007/s00701-008-1551-8.

  2. Helmstaedter C, Loer B, Wohlfahrt R, Hammen A, Saar J, Steinhoff BJ, Quiske A, Schulze-Bonhage A, The effects of cognitive rehabilitation on memory outcome after temporal lobe epilepsy surgery., Epilepsy Behav, 2008, 12, 3, 402-409, doi: 10.1016/j.yebeh.2007.11.010.

  3. Schramm J, Temporal lobe epilepsy surgery and the quest for optimal extent of resection: a review., Epilepsia, 2008, 49, 8, 1296-1307, doi: 10.1111/j.1528-1167.2008.01604.x.

  4. Helmstaedter C, Temporal lobe resection--does the prospect of seizure freedom outweigh the cognitive risks?, Nat Clin Pract Neurol, 2008, 4, 2, 66-67, doi: 10.1038/ncpneuro0657.

  5. Helmstaedter C, Richter S, Röske S, Oltmanns F, Schramm J, Lehmann TN, Differential effects of temporal pole resection with amygdalohippocampectomy versus selective amygdalohippocampectomy on material-specific memory in patients with mesial temporal lobe epilepsy., Epilepsia, 2008, 49, 1, 88-97, doi: 10.1111/j.1528-1167.2007.01386.x.

  6. Weber B, Luders E, Faber J, Richter S, Quesada CM, Urbach H, Thompson PM, Toga AW, Elger CE, Helmstaedter C, Distinct regional atrophy in the corpus callosum of patients with temporal lobe epilepsy., Brain, 2007, 130, Pt 12, 3149-3154, doi: 10.1093/brain/awm186.

  7. Mueller CA, Scorzin J, Koenig R, Urbach H, Fimmers R, Zentner J, Lehmann TN, Schramm J, Comparison of manual tracing versus a semiautomatic radial measurement method in temporal lobe MRI volumetry for pharmacoresistant epilepsy., Neuroradiology, 2007, 49, 3, 189-201, doi: 10.1007/s00234-006-0171-3.

  8. Gleissner U, Sassen R, Schramm J, Elger CE, Helmstaedter C, Greater functional recovery after temporal lobe epilepsy surgery in children., Brain, 2005, 128, Pt 12, 2822-2829, doi: 10.1093/brain/awh597.

  9. Gleissner U, Helmstaedter C, Schramm J, Elger CE, Memory outcome after selective amygdalohippocampectomy in patients with temporal lobe epilepsy: one-year follow-up., Epilepsia, 2004, 45, 8, 960-962, doi: 10.1111/j.0013-9580.2004.42203.x.

  10. Helmstaedter C, Van Roost D, Clusmann H, Urbach H, Elger CE, Schramm J, Collateral brain damage, a potential source of cognitive impairment after selective surgery for control of mesial temporal lobe epilepsy., J. Neurol. Neurosurg. Psychiatr., 2004, 75, 2, 323-326.

  11. Lutz MT, Clusmann H, Elger CE, Schramm J, Helmstaedter C, Neuropsychological outcome after selective amygdalohippocampectomy with transsylvian versus transcortical approach: a randomized prospective clinical trial of surgery for temporal lobe epilepsy., Epilepsia, 2004, 45, 7, 809-816, doi: 10.1111/j.0013-9580.2004.54003.x.

Additional files

Editorial Notes