Zusammenfassung
Fokale kortikale Dysplasien werden zunehmend als Ursache fokaler Epilepsien erkannt.
Sie verursachen oft schon im frühen Kindesalter sich manifestierende, schwere und
meist medikamentös therapierefraktäre Epilepsien, die im Kindesalter nicht selten
zu einer Beeinträchtigung der kognitiven Entwicklung führen können. Die Weiterentwicklung
bildgebender Verfahren ermöglicht es in zunehmendem Maße, fokale kortikale Dysplasien
bei bislang als „kryptogen” eingestuften Epilepsien nachzuweisen und hierdurch den
Weg zu einer Erfolg versprechenden epilepsiechirurgischen Therapie zu eröffnen. Während
weniger als ein Viertel der Patienten eine Anfallskontrolle durch Antiepileptika erzielt,
wird an spezialisierten Zentren heute operativ eine vollständige Anfallskontrolle
bei ca. 60 % der Patienten erreicht. In der vorliegenden Übersicht werden histologische,
klinische, EEG- und MR-Charakteristika fokaler kortikaler Dysplasien und die derzeitigen
therapeutischen Optionen dargestellt.
Abstract
Focal cortical dysplasias are an increasingly recognized etiology of focal epilepsy.
Onset often is during early childhood, seizures may be clinically severe and often
pharmacoresistant and often lead to impairment of psychomotor development. Progress
in imaging techniques allows to increasingly identify focal cortical dysplasias in
formerly „cryptogenic” epilepsies which opens the way for successful surgical therapy.
Whereas seizure control is achieved in less than 25 % of patients by current antiepileptic
drugs, epilepsy surgery in specialized centers leads to seizure freedom in up to 60
% of patients. In this review, histological, clinical, EEG- and MR characteristics
of focal cortical dysplasias as well as therapeutic options are reported.
Literatur
- 1
Sisodiya S M, Free S L, Stevens J M. et al .
Widespread cerebral structural changes in patients with cortical dysgenesis and epilepsy.
Brain.
1995;
118
1039-1050
- 2
Barkovich A J, Kuzniecky R I, Dobyns W B. et al .
A classification scheme for malformations of cortical development.
Neuropediatrics.
1996;
27
59-63
- 3
Rakic P.
Defects of neuronal migration and the pathogenesis of cortical malformations.
Prog Brain Res.
1988;
73
15-37
- 4
Taylor D C, Falconer M A, Bruton C J, Corsellis J A.
Focal dysplasia of the cerebral cortex in epilepsy.
J Neurol Neurosurg Psychiatry.
1971;
34
369-387
- 5
Tassi L, Colombo N, Garbelli R. et al .
Focal cortical dysplasia: neuropathological subtypes, EEG, neuroimaging and surgical
outcome.
Brain.
2002;
125
1719-1732
- 6
Garbelli R, Munari C, Biasi S De. et al .
Taylor's cortical dysplasia: a confocal and ultrastructural immunohistochemical study.
Brain Pathol.
1999;
9
445-446
- 7
Palmini A, Luders H O.
Classification issues in malformations caused by abnormalities of cortical development.
Neurosurg Clin N Am.
2002;
13
1-16
- 8
Palmini A, Najm I, Avanzini G. et al .
Terminology and classification of the cortical dysplasias.
Neurology.
2004;
62
S2-S8
- 9
Hardiman O, Burke T, Phillips J. et al .
Microdysgenesis in resected temporal neocortex: incidence and clinical significance
in focal epilepsy.
Neurology.
1988;
38
1041-1047
- 10
Meyer G, Wahle P, Castaneyra-Perdomo A, Ferres-Torres R.
Morphology of neurons in the white matter of the adult human neocortex.
Exp Brain Res.
1992;
88
204-212
- 11
Kasper B S, Stefan H, Buchfelder M, Paulus W.
Temporal lobe microdysgenesis in epilepsy versus control brains.
J Neuropathol Exp Neurol.
1999;
58
22-28
- 12
Thom M, Sisodiya S, Harkness W, Scaravilli F.
Microdysgenesis in temporal lobe epilepsy. A quantitative and immunohistochemical
study of white matter neurones.
Brain.
2001;
124
2299-2309
- 13
Fauser S.
Mild forms of focal cortical dysplasia: how certain are we?.
Brain.
2005;
128
E23
- 14
Ferrer I, Pineda M, Tallada M. et al .
Abnormal local-circuit neurons in epilepsia partialis continua associated with focal
cortical dysplasia.
Acta Neuropathol (Berl).
1992;
83
647-652
- 15
Ferrer I, Oliver B, Russi A. et al .
Parvalbumin and calbindin-D28 immuno-cytochemistry in human neocortical epileptic
foci.
J Neurol Sci.
1994;
123
18-25
- 16
Spreafico R, Tassi L, Colombo N. et al .
Inhibitory circuits in human dysplastic tissue.
Epilepsia.
2000;
41, Suppl 6
S168-S173
- 17
Ying Z, Babb T L, Comair Y G. et al .
Induced expression of NMDAR2 proteins and differential expression of NMDAR1 splice
variants in dysplastic neurons of human epileptic neocortex.
J Neuropathol Exp Neurol.
1998;
57
47-62
- 18
Najm I M, Ying Z, Babb T. et al .
Epileptogenicity correlated with increased N-methyl-D-aspartate receptor subunit NR2A/B
in human focal cortical dysplasia.
Epilepsia.
2000;
41
971-976
- 19
Crino P B, Duhaime A C, Baltuch G, White R.
Differential expression of glutamate and GABA-A receptor subunit mRNA in cortical
dysplasia.
Neurology.
2001;
56
906-913
- 20
Aronica E, Gorter J A, Jansen G H. et al .
Expression and cell distribution of group I and group II metabotropic glutamate receptor
subtypes in taylor-type focal cortical dysplasia.
Epilepsia.
2003;
44
785-795
- 21
Kerfoot C, Vinters H V, Mathern G W.
Cerebral cortical dysplasia: giant neurons show potential for increased excitation
and axonal plasticity.
Dev Neurosci.
1999;
21
260-270
- 22
Mischel P S, Nguyen L P, Vinters H V.
Cerebral cortical dysplasia associated with pediatric epilepsy. Review of neuropathologic
features and proposal for a grading system.
J Neuropathol Exp Neurol.
1995;
54
137-153
- 23
Prayson R A, Estes M L.
Cortical dysplasia: a histopathologic study of 52 cases of partial lobectomy in patients
with epilepsy.
Hum Pathol.
1995;
26
493-500
- 24
Becker A J, Urbach H, Scheffler B. et al .
Focal cortical dysplasia of Taylor's balloon cell type: mutational analysis of the
TSC1 gene indicates a pathogenic relationship to tuberous sclerosis.
Ann Neurol.
2002;
52
29-37
- 25
Baybis M, Yu J, Lee A. et al .
mTOR cascade activation distinguishes tubers from focal cortical dysplasia.
Ann Neurol.
2004;
56
478-487
- 26
Miyata H, Chiang A C, Vinters H V.
Insulin signaling pathways in cortical dysplasia and TSC-tubers: tissue microarray
analysis.
Ann Neurol.
2004;
56
510-519
- 27
D'Arcangelo G, Miao G G, Chen S C. et al .
A protein related to extracellular matrix proteins deleted in the mouse mutant reeler.
Nature.
1995;
374
719-723
- 28
Caviness V SJ, Rakic P.
Mechanisms of cortical development: a view from mutations in mice.
Ann Rev Neurosc.
1978;
1
297-326
- 29
Roper S N, Abraham L A, Streit W.
Exposure to in utero irradiation produces disruption of radial gila in rats.
Dev Neurosci.
1997;
19
521-527
- 30
Roper S N.
In utero irradiation of rats as a model of human cerebrocortical dysgenesis: a review.
Epilepsy Res.
1998;
32
63-74
- 31
Sun X Z, Inouye M, Fukui Y. et al .
An immunohistochemical study of radial glial cells in the mouse brain prenatally exposed
to gamma-irradiation.
J Neuropathol Exp Neurol.
1997;
56
1339-1348
- 32
Colacitti C, Sancini G, Biasi S De. et al .
Prenatal methylazoxymethanol treatment in rats produces brain abnormalities with morphological
similarities to human developmental brain dysgeneses.
J Neuropathol Exp Neurol.
1999;
58
92-106
- 33
Redecker C, Lutzenburg M, Gressens P. et al .
Excitability changes and glucose metabolism in experimentally induced focal cortical
dysplasias.
Cereb Cortex.
1998;
8
623-634
- 34
Jacobs K M, Gutnick M J, Prince D A.
Hyperexcitability in a model of cortical maldevelopment.
Cereb Cortex.
1996;
6
514-523
- 35
Chevassus-au-Louis N, Ben-Ari Y, Vergnes M.
Decreased seizure threshold and more rapid rate of kindling in rats with crtical malformation
induced by prenatal treatment with methylazosymethanol.
Brain Res.
1998;
812
252-255
- 36
Lee K S, Schottler F, Collins J L. et al .
A genetic animal model of human neocortical heterotopia associated with seizures.
J Neurosci.
1997;
17
6236-6242
- 37
Mattia D, Olivier A, Avoli M.
Seizure-like discharges recorded in human dysplastic neocortex maintained in vitro.
Neurology.
1995;
45
1391-1395
- 38
Avoli M, Bernasconi A, Mattia D. et al .
Epileptiform discharges in the human dysplastic neocortex: in vitro physiology and
pharmacology.
Ann Neurol.
1999;
46
816-826
- 39
Crino P B, Eberwine J.
Cellular and molecular basis of cerebral dysgenesis.
J Neurosci Res.
1997;
50
907-916
- 40
D'Antuono M, Louvel J, Köhling R. et al .
GABAA receptor-dependent synchronization leads to ictogenesis in the human dysplastic cortex.
Brain.
2004;
127
1626-1640
- 41
Spreafico R, Pasquier B, Minotti L. et al .
Immunocytochemical investigation on dysplastic human tissue from epileptic patients.
Epilepsy Res.
1998;
32
34-48
- 42
Mikuni N, Nishiyama K, Babb T L. et al .
Decreased calmodulin-NR1 co-assembly as a mechanism for focal epilepsy in cortical
dysplasia.
Neuroreport.
1999;
10
1609-1612
- 43
Palmini A, Andermann F, Olivier A. et al .
Focal neuronal migration disorders and intractable partial epilepsy: results of surgical
treatment.
Ann Neurol.
1991;
30
750-757
- 44
Desbiens R, Berkovic S F, Dubeau F. et al .
Life-threatening focal status epilepticus due to occult cortical dysplasia.
Arch Neurol.
1993;
50
695-700
- 45
Kuzniecky R, Powers R.
Epilepsia partialis continua due to cortical dysplasia.
J Child Neurol.
1993;
8
386-388
- 46
Palmini A, Costa da Costa J, Andermann F. et al .
Epilepsia partialis continua associated with cortical dysplasia: delineation of the
syndrome (Abstr.).
Epilepsia.
1997;
38, Suppl 3
160
- 47
Alonso-Nanclares L, Garbelli R, Sola R G. et al .
Microanatomy of the dysplastic neocortex from epileptic patients.
Brain.
2005;
128
158-173
- 48
Boonyapisit K, Najm I, Klem G. et al .
Epileptogenicity of focal malformations due to abnormal cortical development: direct
electrocorticographic-histopathologic correlations.
Epilepsia.
2003;
44
69-76
- 49
Bautista R E, Cobbs M A, Spencer D D, Spencer S S.
Prediction of surgical outcome by interictal epileptiform abnormalities during intracranial
EEG monitoring in patients with extrahippocampal seizures.
Epilepsia.
1999;
40
880-890
- 50
Lortie A, Plouin P, Chiron C. et al .
Characteristics of epilepsy in focal cortical dysplasia in infancy.
Epilepsy Res.
2002;
51
133-145
- 51
Barkovich A J, Kuzniecky R I, Jachson G D, Dobyns W B.
Classification systems for malformation of cortical development. Update 2001.
Neurology.
2001;
57
2168-2178
- 52
Kassubek J, Huppertz H J, Spreer J, Schulze-Bonhage A.
Detection and localization of focal cortical dysplasia by voxel-based 3-D MRI analysis.
Epilepsia.
2002;
43
596-602
- 53 Polkey C E.
Cortical dysplasia: resective surgery in children. In: Guerrini R, Andermann F, Canapicchi R, Roger J, Zifkin BG, Pfanner P (eds) Dysplasias
of Cerebral Cortex and Epilepsy. Philadelphia; Lippincott-Raven 1996: 435-439
- 54
Wyllie E, Comair Y G, Kotagal P. et al .
Seizure outcome after epilepsy surgery in children and adolescents.
Ann Neurol.
1998;
44
740-748
- 55
Marchal G, Andermann F, Tampieri D. et al .
Generalized cortical dysplasia manifested by diffusely thick cerebral cortex.
Arch Neurol.
1989;
46
430-434
- 56
Raymond A A, Fish D R, Sisodiya S M. et al .
Abnormalities of gyration, heterotopias, tuberous sclerosis, focal cortical dysplasia,
microdysgenesis, dysembryoblastic neuroepithelial tumor and dysgenesis of the archicortex
in epilepsy: clinical, EEG and neuroimaging features in 100 adult patients.
Brain.
1995;
118
629-660
- 57
Barkovich A J, Kuzniecky R I.
Neuroimaging of focal malformations of cortical development.
J Clin Neurophysiol.
1996;
13
481-494
- 58
Barkovich A J.
Magnetic resonance imaging: role in the understanding of cerebral malformations.
Brain Dev.
2002;
24
2-12
- 59
Urbach H, Scheffler B, Heinrichsmeier T. et al .
Focal cortical dysplasia of Taylor's balloon cell type: a clinicopathological entity
with characteristic neuroimaging and histopathological features, and favorable postsurgical
outcome.
Epilepsia.
2002;
43
33-40
- 60
Barkovich A J, Kuzniecky R I, Bollen A W, Grant P E.
Focal transmantle dysplasia: a specific malformation of cortical development.
Neurology.
1997;
49
1148-1152
- 61
Kuzniecky R, Mountz J M, Wheatley G, Morawetz R.
Ictal single-photon emission computed tomography demonstrates localized epileptogenesis
in cortical dysplasia.
Ann Neurol.
1993;
34
627-631
- 62
Huppertz H J.
Voxel-based 3D-MRI-analysis for the detection of focal cortical dysplasia.
Klin Neurophysiol.
2004;
35
156
- 63
Ruggieri P M, Najm I, Bronen R. et al .
Neuroimaging of the cortical dysplasias.
Neurology.
2004;
62, 6 Suppl 3
S27-29
- 64
Bastos A C, Korah I P, Cendes F. et al .
Curvilinear reconstruction of 3D magnetic resonance imaging in patients with partial
epilepsy: a pilot study.
Magn Reson Imaging.
1995;
13
1107-1112
- 65
Bastos A C, Comeau R M, Andermann F. et al .
Diagnosis of subtle focal dysplastic lesions: curvilinear reformatting from three-dimensional
magnetic resonance imaging.
Ann Neurol.
1999;
46
88-94
- 66
Schulze-Bonhage A H, Huppertz H J, Comeau R M. et al .
Visualization of subdural strip and grid electrodes using curvilinear reformatting
of 3D MR imaging data sets.
AJNR Am J Neuroradiol.
2002;
23
400-403
- 67
Woermann F G, Free S L, Koepp M J. et al .
Voxel-by-voxel comparison of automatically segmented cerebral gray matter- A rater-independent
comparison of structural MRI in patients with epilepsy.
Neuroimage.
1999;
10
373-384
- 68
Fischl B, Dale A M.
Measuring the thickness of the human cerebral cortex from magnetic resonance images.
Proc Natl Acad Sci USA.
2000;
97
11050-11055
- 69
Merschhemke M, Mitchell T N, Free S L. et al .
Quantitative MRI detects abnormalities in relatives of patients with epilepsy and
malformations of cortical development.
Neuroimage.
2003;
18
642-649
- 70
Bernasconi A, Antel S B, Collins D L. et al .
Texture analysis and morphological processing of magnetic resonance imaging assist
detection of focal cortical dysplasia in extra-temporal partial epilepsy.
Ann Neurol.
2001;
49
770-775
- 71
Antel S B, Bernasconi A, Bernasconi N. et al .
Computational models of MRI characteristics of focal cortical dysplasia improve lesion
detection.
Neuroimage.
2002;
17
1755-1760
- 72
Antel S B, Collins D L, Bernasconi N. et al .
Automated detection of focal cortical dysplasia lesions using computational models
of their MRI characteristics and texture analysis.
Neuroimage.
2003;
19
1748-1759
- 73
Ashburner J, Friston K J.
Nonlinear spatial normalization using basis functions.
Hum Brain Mapp.
1999;
7
254-266
- 74
Ashburner J, Friston K J.
Voxel-based morphometry - The methods.
Neuroimage.
2000;
11
805-821
- 75
Ashburner J, Friston K J.
Why voxel-based morphometry should be used.
Neuroimage.
2001;
14
1238-1243
- 76
Wilke M, Kassubek J, Ziyeh S. et al .
Automated detection of gray matter malformations using optimized voxel-based morphometry:
a systematic approach.
Neuroimage.
2003;
20
330-343
- 77
Palmini A, Gambardella A, Andermann F. et al .
Intrinsic epileptogenicity of human dysplastic cortex as suggested by corticography
and surgical results.
Ann Neurol.
1995;
37
476-487
- 78
Gambardella A, Palmini A, Andermann F. et al .
Usefulness of focal rhythmic discharges on scalp EEG of patients with focal cortical
dysplasia and intractable epilepsy.
Electroencephalogr Clin Neurophysiol.
1996;
98
243-249
- 79
Guerrini R, Dravet C, Raybaud C. et al .
Epilepsy and focal gyral anomalies detected by MRI: electroclinico-morphological correlations
and follow-up.
Dev Med Child Neurol.
1992;
34
706-718
- 80
Ambrosetto G.
Treatable partial epilepsy and unilateral opercular neuronal migration disorder.
Epilepsia.
1993;
34
604-608
- 81
Chugani H T, Shields W D, Shewmon D A. et al .
Infantile spasms: I. PET identifies focal cortical dysgenesis in cryptogenic cases
for surgical treatment.
Ann Neurol.
1990;
27
406-413
- 82
Arnold S, Berthele A, Drzezga A. et al .
Reduction of benzodiazepine receptor binding is related to the seizure onset zone
in extratemporal focal cortical dysplasia.
Epilepsia.
2000;
41
818-824
- 83
Hammers A, Koepp M J, Richardson M P. et al .
Central benzodiazepine receptors in malformations of cortical development: A quantitative
study.
Brain.
2001;
124
1555-1565
- 84
O'Brien T J, So E L, Cascino G D. et al .
Subtraction SPECT coregistered to MRI in focal malformations of cortical development:
localization of the epileptogenic zone in epilepsy surgery candidates.
Epilepsia.
2004;
45
367-376
- 85
Gupta A, Raja S, Kotagal P. et al .
Ictal SPECT in children with partial epilepsy due to focal cortical dysplasia.
Pediatr Neurol.
2004;
31
89-95
- 86
Matsuda K, Mihara T, Tottori T. et al .
Neuroradiologic findings in focal cortical dysplasia: histologic correlation with
surgically resected specimens.
Epilepsia.
2001;
42, S6
29-36
- 87
Elterman R D, Shields W D, Mansfield K A. et al .
Randomized trial of vigabatrin in patients with infantile spasms.
Neurology.
2001;
57
1412-1416
- 88
Hancock E, Osborne J P.
Vigabatrin in the treatment of infantile spasms in tuberous sclerosis: literature
review.
J Child Neurol.
1999;
14
71-74
- 89 Cieuta C, Guerrini R, Ferrari A R, Dulac O.
Antiepileptic drug treatment and intractability of epilepsy related to cortical dysplasia. In: Guerrini R, Canapicchi R, Zifkin BG, Anderman F, Roger J, Pfanner P (eds) Dysplasias
of Cerebral Cortex and Epilepsy. Philadelphia, New York; Lippincott-Raven 1996: 337-344
- 90
Semah F, Picot M C, Adam C. et al .
Is the underlying cause of epilepsy a major prognostic factor for recurrence?.
Neurology.
1998;
51
1256-1262
- 91
Stephen L J, Kwan P, Brodie M J.
Does the cause of localisation-related epilepsy influence the response to antiepileptic
drug treatment?.
Epilepsia.
2001;
42
357-362
- 92
Sisodiya S M.
Surgery for malformations of cortical development causing epilepsy.
Brain.
2000;
123
1075-1091
- 93 Andermann F.
Brain structure in epilepsy. In: Shorvon SD, Fisher DR, Andermann F, Bydder GM, Stefan H (eds) Magnetic Resonance
Scanning and Epilepsy. New York; Plenum Press 1994: 21-27
- 94
Rosenow F, Lüders H O, Dinner D S. et al .
Histopathological correlates of epileptogenicity as expressed by electrographic spiking
and seizure frequency.
Epilepsia.
1998;
39
850-856
- 95
Bautista J F, Foldvary-Schaefer N, Bingaman W E, Lüders H O.
Focal cortical dysplasia and intractable epilepsy in adults: clinical, EEG, Imaging,
and surgical features.
Epilepsy Res.
2003;
55
131-136
- 96
Hirabayashi S, Binnie C D, Janota I, Polkey C E.
Surgical treatment of epilepsy due to cortical dysplasia: clinical and EEG findings.
J Neurol Neurosurg Psychiatry.
1993;
56
765-770
- 97
Richardson M P, Koepp M J, Brooks D J. et al .
Cerebral activation in malformations of cortical development.
Brain.
1998;
121
1295-1330
- 98
Janszky J, Ebner A, Kruse B. et al .
Functional organization of the brain with malformations of cortical development.
Ann Neurol.
2003;
53
759-767
- 99
Chassoux F, Devaux B, Landre E. et al .
Stereoelectroencephalography in focal cortical dysplasia: a 3D approach to delineating
the dysplastic cortex.
Brain.
2000;
123
1733-1751
- 100
Kloss S, Pieper T, Pannek H. et al .
Epilepsy surgery in children with focal cortical dysplasia (FCD): results of long-term
seizure outcome.
Neuropediatrics.
2002;
33
21-26
- 101
Kral T, Clusmann H, Blumcke I. et al .
Outcome of epilepsy surgery in focal cortical dysplasia.
J Neurol Neurosurg Psychiatry.
2003;
74
183-188
- 102
Fauser S, Schulze-Bonhage A, Honegger J. et al .
Focal cortical dysplasias: surgical outcome in 67 patients in relation to histological
subtypes and dual pathology.
Brain.
2004;
127
2406-2418
- 103
Keene D L, Jimenez C C, Ventureyra E.
Cortical microdysplasia and surgical outcome in refractory epilepsy of childhood.
Pediatr Neurosurg.
1998;
55
131-136
- 104
Palmini A, Gambardella A, Andermann F. et al .
Operative strategies for patients with cortical dysplastic lesions and intractable
epilepsy.
Epilepsia.
1994;
35
57-71
- 105
Prayson R A, Frater J L.
Cortical dysplasia in extratemporal lobe intractable epilepsy: a study of 52 cases.
Ann diagn Pathol.
2003;
7
139-146
- 106
Sisodiya S M.
Surgery for focal cortical dysplasia.
Brain.
2004;
127
2383-2384
PD Dr. Andreas Schulze-Bonhage
Epilepsiezentrum · Neurozentrum des Universitätsklinikum Freiburg
Breisacher Straße 64
79106 Freiburg
Email: schulzeb@nz.ukl.uni-freiburg.de
