Novel pathological abnormalities of deep brain structures including dysplastic neurons in anterior striatum associated with focal cortical dysplasia in epilepsy

Clinical article

Restricted access

Object

Some patients are not seizure free even after epileptogenic cortical resection. The authors recently described a case of frontal lobe epilepsy cured after the resection of periventricular white matter and striatum, in which dysplastic neurons were revealed. The authors attempted to confirm similar cases.

Methods

They reviewed the records of 8 children with frontal lobe epilepsy who had daily (7) or monthly (1) seizures and underwent resections including deep brain structures.

Results

Five patients underwent multiple resections. Neuroimaging of the deep structures showed the transmantle sign in 3 patients, ictal hyperperfusion in 6, reduced iomazenil uptake in 2, and spike dipole clustering in 6. All patients became seizure free postoperatively. Focal cortical dysplasia of various types was diagnosed in all patients. Dysmorphic neurons were found in the cortex and subcortical white matter of 5 patients. The striatum was verified in 3 patients in whom dysmorphic neurons were scattered. In the periventricular white matter, prominent astrocytosis was evident in all cases.

Conclusions

Pathological abnormalities such as dysmorphic neurons and astrocytosis in deep brain structures would play a key role in epileptogenesis.

Abbreviations used in this paper:ECoG = electrocorticography; EEG = electroencephalography; FCD = focal cortical dysplasia; GABA = γ-aminobutyric acid; MEG = magnetoencephalography.

Article Information

Address correspondence to: Takanobu Kaido, M.D., Department of Neurosurgery, Epilepsy Center, National Center of Neurology and Psychiatry, Ogawahigashicho 4-1-1, Kodaira, Tokyo 187-8551, Japan. email: kaido@ncnp.go.jp.

* Drs. Kaido and Otsuki contributed equally to this work.

Please include this information when citing this paper: published online July 27, 2012; DOI: 10.3171/2012.6.PEDS11325.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Case 4. A–C: Preoperative MR images showing blurring of gray matter–white matter in the left frontal lobe. D–F: Preoperative magnetoencephalograms showing a cluster of spike dipoles in the deep white matter of the left frontal lobe. Dipole sources with a goodness-of-fit better than 90% (yellow squares) and 80% (green circles) were accepted and overlaid on the MRI results. A somatosensory evoked magnetic field was obtained on stimulation of the right median nerve (red circle). G–I: Magnetoencephalograms obtained after the first frontal lobe disconnection surgery, revealing a cluster of spike dipoles in the deep white matter of the residual frontal lobe. J–L: Magnetoencephalograms obtained after a second partial frontal lobectomy, revealing a cluster of spike dipoles in the head of the caudate nucleus and the deep white matter of the residual frontal lobe. M–O: Subtraction ictal SPECT coregistered with structural MRI (SISCOM) revealing hyperperfusion of the nucleus accumbens and the deep white matter of the left frontal lobe. P–R: Magnetoencephalograms obtained after the third surgery, a partial resection of the anterior striatum and residual frontal lobe, showing a cluster of spike dipoles mostly in the disconnected frontal lobe and slightly in the margin of the residual brain tissue.

  • View in gallery

    Case 6. A–C: Preoperative MR images showing blurring of gray matter–white matter in the right frontal lobe and the transmantle sign, that is, signal abnormalities extending radially inward toward the lateral ventricle from the cortical surface (arrows). D–F: 123I-iomazenil SPECT scans revealing low uptake at the right frontal lobe. G–I: Ictal SPECT scans showing significant hyperperfusion in the white matter of the right frontal lobe. J–L: Postoperative MR images obtained after resection of the right frontal lobe and the periventricular white matter.

  • View in gallery

    Photomicrographs showing histopathological features of resected tissue. Case 4. A: Low-magnification view of cortex demonstrating the polymicrogyric cortical ribbon. B: High-magnification view of cortex showing several dysmorphic neurons. C: Area with abnormally blurred transition from the cortex (upper) to the subcortical white matter (lower). D: A heterotopic neuronal nest (asterisk) within the white matter E: Two dysmorphic neurons (arrows) in the insular cortex. F: Low-magnification view of the area close to the ventricle (vent) demonstrating orientation of the subventricular zone (SVZ) and the anterior caudate head (ch). Arrows indicate the ependymal cell lining. Inset: Higher magnification of the area indicated by a square in F, showing small ependymal canals (forking). G: Two dysmorphic neurons (arrows) within or adjacent to the axon bundles (pencil fibers [p]) in the striatum. H: A dysmorphic neuron in the periventricular white matter. Case 6. I: Dysmorphic neurons in the cortex. J: Many neurons are scattered in the deeper layers of the cortex (upper) and underlying white matter (lower). K: Dysmorphic neurons distributing parallel to the direction of myelinated fibers in the deep white matter. L: Prominent reactive astrocytosis in the periventricular white matter. Klüver-Barrera stain (A–D, F–H, J, and K), H & E (E, Inset, and I), and glial fibrillary acidic protein immunostaining with diaminobenzidine as the chromogen (L). Bar (all in μm) = 770 (A), 40 (B, G, and I), 385 (C), 520 (D), 25 (E), 800 (F), 30 (Inset), 15 (H), 155 (J), 100 (K), and 75 (L).

References

  • 1

    Aghakhani YKinay DGotman JSoualmi LAndermann FOlivier A: The role of periventricular nodular heterotopia in epileptogenesis. Brain 128:6416512005

    • Search Google Scholar
    • Export Citation
  • 2

    Alonso-Nanclares LGarbelli RSola RGPastor JTassi LSpreafico R: Microanatomy of the dysplastic neocortex from epileptic patients. Brain 128:1581732005

    • Search Google Scholar
    • Export Citation
  • 3

    Annergers JThe epidemiology of epilepsy. Wyllie E: The Treatment of Epilepsy Principles and Practice ed 3PhiladelphiaLippincott Williams & Wilkins2001. 131138

    • Search Google Scholar
    • Export Citation
  • 4

    Barkovich AJKuzniecky RIBollen AWGrant PE: Focal transmantle dysplasia: a specific malformation of cortical development. Neurology 49:114811521997

    • Search Google Scholar
    • Export Citation
  • 5

    Boatman DFreeman JVining EPulsifer MMiglioretti DMinahan R: Language recovery after left hemispherectomy in children with late-onset seizures. Ann Neurol 46:5795861999

    • Search Google Scholar
    • Export Citation
  • 6

    Cook SWNguyen STHu BYudovin SShields WDVinters HV: Cerebral hemispherectomy in pediatric patients with epilepsy: comparison of three techniques by pathological substrate in 115 patients. J Neurosurg 100:2 Suppl Pediatrics1251412004

    • Search Google Scholar
    • Export Citation
  • 7

    Gastaut HGastaut JLRégis HBernard RPinsard NSaint-Jean M: Computerized tomography in the study of West's syndrome. Dev Med Child Neurol 20:21271978

    • Search Google Scholar
    • Export Citation
  • 8

    Hannan AJServotte SKatsnelson ASisodiya SBlakemore CSquier M: Characterization of nodular neuronal heterotopia in children. Brain 122:2192381999

    • Search Google Scholar
    • Export Citation
  • 9

    Jacobs KMDonoghue JP: Reshaping the cortical motor map by unmasking latent intracortical connections. Science 251:9449471991

  • 10

    Johnston MV: Plasticity in the developing brain: implications for rehabilitation. Dev Disabil Res Rev 15:941012009

  • 11

    Kaido TOtsuki TKaneko YTakahashi AKakita ATakahashi H: Anterior striatum with dysmorphic neurons associated with the epileptogenesis of focal cortical dysplasia. Seizure 19:2562592010

    • Search Google Scholar
    • Export Citation
  • 12

    Kakita AKameyama SHayashi SMasuda HTakahashi H: Pathologic features of dysplasia and accompanying alterations observed in surgical specimens from patients with intractable epilepsy. J Child Neurol 20:3413502005

    • Search Google Scholar
    • Export Citation
  • 13

    Kriegstein AOwens DBrain development milestones and pathologic correlation. Wyllie E: The Treatment of Epilepsy Principles and Practice ed 3PhiladelphiaLippincott Williams & Wilkins2001. 4564

    • Search Google Scholar
    • Export Citation
  • 14

    Krsek PPieper TKarlmeier AHildebrandt MKolodziejczyk DWinkler P: Different presurgical characteristics and seizure outcomes in children with focal cortical dysplasia type I or II. Epilepsia 50:1251372009

    • Search Google Scholar
    • Export Citation
  • 15

    Nakayama TOtsuki TKaneko YNakama HKaido TOtsubo H: Repeat magnetoencephalography and surgeries to eliminate atonic seizures of non-lesional frontal lobe epilepsy. Epilepsy Res 84:2632672009

    • Search Google Scholar
    • Export Citation
  • 16

    Nguyen DKNguyen DBMalak RLeroux JMCarmant LSaint-Hilaire JM: Revisiting the role of the insula in refractory partial epilepsy. Epilepsia 50:5105202009

    • Search Google Scholar
    • Export Citation
  • 17

    Palmini ANajm IAvanzini GBabb TGuerrini RFoldvary-Schaefer N: Terminology and classification of the cortical dysplasias. Neurology 62:6 Suppl 3S2S82004

    • Search Google Scholar
    • Export Citation
  • 18

    RamachandranNair ROchi AAkiyama TBuckley DJSoman TBWeiss SK: Partial seizures triggering infantile spasms in the presence of a basal ganglia glioma. Epileptic Disord 7:3783822005

    • Search Google Scholar
    • Export Citation
  • 19

    Sasaki MMatsuda HOmura ISugai KHashimoto T: Transient seizure disappearance due to bilateral striatal necrosis in a patient with intractable epilepsy. Brain Dev 22:50552000

    • Search Google Scholar
    • Export Citation
  • 20

    Schönberger ANiehusmann PUrbach HMajores MGrote AHolthausen H: Increased frequency of distinct TSC2 allelic variants in focal cortical dysplasias with balloon cells and mineralization. Neuropathology 29:5595652009

    • Search Google Scholar
    • Export Citation
  • 21

    Sisodiya SMSquier MVAnslow AMalformation of cortical development. Oxbury JPolkey CDuchowny M: Intractable Focal Epilepsy LondonW.B. Saunders2000. 99130

    • Search Google Scholar
    • Export Citation
  • 22

    Talairach JBancaud J: Lesion, “irritative” zone and epileptogenic focus. Confin Neurol 27:91941966

  • 23

    Widdess-Walsh PDiehl BNajm I: Neuroimaging of focal cortical dysplasia. J Neuroimaging 16:1851962006

  • 24

    Wieser HGBlume WTFish DGoldensohn EHufnagel AKing D: ILAE Commission Report. Proposal for a new classification of outcome with respect to epileptic seizures following epilepsy surgery. Epilepsia 42:2822862001

    • Search Google Scholar
    • Export Citation

Cited By

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 103 103 17
Full Text Views 58 58 0
PDF Downloads 98 98 0
EPUB Downloads 0 0 0

PubMed

Google Scholar