The Child with Intractable Epilepsy

1. The Child with Intractable
Epilepsy
Erin Simon Schwartz, MD, FACR
Associate Professor of Radiology
Perelman School of Medicine, University of Pennsylvania
Medical Director, Lurie Family Foundations’ Magnetoencephalography
Imaging Center
The Children’s Hospital of Philadelphia

2. Disclosures
• None

3. Overview
• Common Etiologies – Focal Cortical
Dysplasia
– Types I and IIa are commonly missed
• Acquired lesions (ischemia, trauma,
inflammation, hemorrhage, neoplasia)
• Structural and Functional Imaging
– High resolution, volumetric MRI with DTI - SPECT
-MRS - PET
– Magnetoencephalography (MEG)

4. Epilepsy
• 30,000 new pediatric cases annually
– ~25% medically refractory
• Surgical treatment of drug-resistant epilepsy increasingly utilized
for children and adults
• Concordance of clinical & multimodal imaging findings  higher
likelihood postop seizure freedom
• Nonlesional MRIs reported in 16-47%, many MRI-negative
patients undergo invasive EEG monitoring prior to resection, or
are not offered surgery
• Postoperative seizure freedom rates in patients with nonlesional
MRIs vary, typically 40-50%

5. ILAE Consensus Classification
• Type I
– Ia: FCD with abnormal radial cortical lamination
– Ib: FCD with abnormal tangential cortical lamination
– Ic: FCD with abnormal radial and tangential cortical lamination
• Type II
– IIa: FCD with dysmorphic neurons
– IIb: FCD with dysmorphic neurons and balloon cells
• Type III = Cortical lamination abnormalities:
– IIIa: In temporal lobe, assoc with hippocampal sclerosis
– IIIb: Adjacent to a glial or glioneuronal tumor
– IIIc: Adjacent to a vascular malformation
– IIId: Adjacent to any other lesion acquired during early life (i.e. trauma,
ischemic injury, encephalitis)

6. FCD Type I (Isolated)
• Ia: FCD with abnormal radial cortical lamination
• Ib: FCD with abnormal tangential cortical lamination
• Ic: FCD with abnormal radial and tangential cortical lamination
• Imaging findings, although usually not visible on MRI, may
include:
– Segmental or lobar hypoplasia/atrophy, often with reduced
volume at the gray-white matter junction
– Abnormal sulcal/gyral pattern
– Ib more often extratemporal

7. FCD Type Ia - with abnormal radial lamination
“Usually not visible on MRI”, may see:
Segmental or lobar hypoplasia/atrophy, often with reduced
volume at the gray-white matter junction,
abnormal sulcal/gyral pattern

8. FCD Type Ia

9. FCD Type Ia
Normal (NeuN stain) Abnormal vertical
microcolumns of cells
Courtesy of B Harding

10. FCD Type II (Isolated)
• IIa: FCD with dysmorphic neurons
• Imaging findings:
– Not always seen on MRI
– May see blurring of gray-white junction
– More difficult to identify than Type IIb

11. FCD Type IIa - with dysmorphic neurons

12. FCD Type IIa

13. FCD IIa

14. FCD Type IIa

15. FCD Type IIa
Large dysmorphic neurons
scattered throughout cortex
(H&E)
Abnormal neurons with
neurofilament staining
Courtesy of B Harding

16. FCD Type II (Isolated)
• IIb: FCD with dysmorphic neurons and balloon cells
• Imaging findings:
– Blurring of the gray-white matter junction on T1WI
– Increased subcortical white matter signal on T2WI and T2
FLAIR images
– Transmantle dysplasia – white matter signal abnormality
tapers from crown of gyrus or bottom of sulcus towards
ventricle, usually frontal
– Abnormal cortical gyration/sulcation, may be seen as focal
enlargement of overlying subarachnoid space

17. FCD Type IIb

18. FCD Type IIb

19. Transmantle dysplasia
FCD Type IIb

20. FCD Type IIb

21. FCD Type IIb

22. FCD Type IIb
Loss of normal lamination due
to many dysmorphic large
neurons (H&E)
Balloon cells (B) scattered
among abnormal neurons (N)
B
N
Courtesy of B Harding

23. FCD Type III (Associated with
Principal Lesion)
• Cortical lamination abnormalities:
• IIIa: In the temporal lobe associated with
hippocampal sclerosis
• IIIb: Adjacent to a glial or glioneuronal tumor
• IIIc: Adjacent to a vascular malformation
• IIId: Adjacent to any other lesion acquired
during early life (eg, trauma, ischemic injury,
encephalitis)

24. FCD Type IIIa

25. FCD Type IIIb
Ganglioglioma with FCD

26. FCD Type IIIc

27. Acute HSV
encephalitis
FCD Type IIId

28. FCD Type IIId
Three years later

29. ILAE Consensus Classification
• Type I
– Ia: FCD with abnormal radial cortical lamination
– Ib: FCD with abnormal tangential cortical lamination
– Ic: FCD with abnormal radial and tangential cortical lamination
• Type II
– IIa: FCD with dysmorphic neurons
– IIb: FCD with dysmorphic neurons and balloon cells
• Type III = Cortical lamination abnormalities:
– IIIa: In temporal lobe, assoc with hippocampal sclerosis
– IIIb: Adjacent to a glial or glioneuronal tumor
– IIIc: Adjacent to a vascular malformation
– IIId: Adjacent to any other lesion acquired during early life (i.e. trauma,
ischemic injury, encephalitis)

30. Magnetoencephalography
• Localizes regions of
abnormal interictal activity
• Localizes regions of normal
functional activity
– Language
– Vision
– Motor
– Somatosensory

31. 11y M, SS: R Lower extremity, trunk, shoulder
somatosensory  motor
EEG: L posterior frontal

32. Motor Mapping: RD2

37. 6y Male, suspected R anterior temporal by scalp EEG

38. Intracranial
Recordings
Confirmed Two
Independent Sites

39. 11y M, SS: bilateral eye blinking, followed by left arm
stiffening with clenched fist, followed by bilateral leg
stiffening
EEG: right central or central midline onset

40. 12345678
910111213141516
1718192021222324
2526272829303132
Motor Mapping:
Green = L hand
Purple = L face
Motor strip = 5, 14, 22, 30
Courtesy of M Fitzgerald

41. Courtesy of B Kennedy

42. 13y M, SS: bilateral arm raising
EEG: Bifrontal, Left > Right

49. Multimodal Integration
• Focal findings detected with one modality
can result in multimodal confirmation and
improve outcome
– MEG & MRI
– PET & MRI
– PET, MEG, & MRI

50. • May 2016-June 2017
• Six (31.6%) of 19 MRIs initially clinically interpreted as nonlesional were
retrospectively found to have an abnormality on MRI at a site of abnormal
interictal MEG activity
– 3 Focal cortical dysplasia
– 2 Abnormal gyral pattern, presumed FCD
– 1 Subependymal gray matter heterotopia
• Correlating MEG findings with “nonlesional” MRIs can increase
lesion detection rate, add to value of preoperative MEG in
improving patient selection and outcome
Schwartz, et al, ASFNR 2017
Review of Nonlesional Brain MRIs with Attention to MEG
Epileptogenic Zones Detects Focal Lesions

51. Example – 12yM
• Two seizure types:
– Creepy laughing
– Grunting & stiffening of extremities
– Remote history: Aura of RLE paresthesias
• Scalp EEG: Cz or Pz onset, field to P3
• MRI: Read as normal

52. MEG: Abnormal sharp interictal activity left
parasagittal posterior parietal lobe
(same reader as MRI)

53. MRI Review: Abnormal signal/blurred gray-white
differentiation, subcortical white matter of left parasagittal
posterior parietal lobe

54. Example – 45yF
• Prior traumatic brain injury
• Scalp EEG: Nonfocal
• MRI: Normal

55. MEG: Rare sharp interictal activity right posterior
temporal/occip/parietal junction

56. MRI Review: Abnormal gyral pattern with focally prominent
overlying subarachnoid space

57. Example – 30yF
• Predominately behavioral arrest and automatisms
• Scalp EEG: independent left
and right anterior temporal activity
• MRI: Normal

58. • MEG: abnormal interictal sharp activity left medial
temporal lobe, less commonly to right medial temporal
lobe

59. MRI Review: Bilateral subependymal gray matter
heterotopia

61. PET Courtesy of J Dubroff
Example – 35yF

62. Epilepsy
• Multimodal structural and functional imaging
options for the detection of epileptogenic foci
(most commonly FCD)
–MRI with DTI
–MEG
–PET
• Clinical and multimodal concordance favors
better outcome

63. MEG Center Director: Timothy PL Roberts PhD
Technologists: Lead -John Dell
Rachel Golembski, Peter Lam, Erin Huppman, Na’Keisha Robinson
William C Gaetz, PhD
Hao Huang, PhD
Arastoo Vossough, MD, PhD
Deborah M Zarnow, MD
Jeffery Berman, PhD
Lisa Blaskey, PhD
Luke Bloy, PhD
Yu-han Chen, PhD
J Christopher Edgar, PhD