1. Gloria J. Guzmán, MD, MSc Robert McKinstry, MD, PhD Matthew Smyth, MD, FAANS, FACS, FAAP

2. Financial Disclosures Gloria Guzman and Matthew Smyth: None Robert McKinstry: Siemens Healthcare: Honoraria, travel, lodging, meals >$10,000

3. PURPOSE

4. To create an imaging primer that will allow easier radiographic identification of focal cortical dysplasias

5. APPROACH/METHODS

6. What is focal cortical dysplasia (FCD)? 1, 2 Focal cortical dysplasia is a derangement of cortical development, including neuronal proliferation, migration, differentiation or programmed cell death Both genetic and acquired factors are involved, although the pathogenesis is still being investigated Multiple grading systems exist. In general, three types are recognized (I, II and III), each with associated sub- classifications. We will focus on FCD type I and II, which are isolated lesions. FCD type III are associated with other findings, such as tumor, vascular malformations or sclerosis 1.Colombo et at. Imaging of malformations of cortical development. Epileptic Disord 2009; 11 (3): 194-205 2.Blümcke et al. The clinicopathologic spectrum of focal cortical dysplasias: A consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission. Epilepsia, 52(1):158–174, 2011

7. Imaging findings of FCD Type I 1, 2 Temporal predilection, more common in adults Prominent lobar/sublobar hypoplasia/atrophy, frequently associated with volume loss of the subcortical white matter: Moderately increased signal on T2WI and heavily T2W FLAIR images Decreased signal on T1W images, either 3D volumetric Gradient Echo T1W or heavily T1W Inversion Recovery (IR) images Mild blurring at the grey/white matter junction with normal cortical thickness Abnormal gyral/sulcal patterns can be present Most commonly associated with dual pathology (+ hippocampal sclerosis) 1, which will not be discussed in this presentation, as it is “not yet comprehensively defined” 2 1.Colombo et at. Imaging of malformations of cortical development. Epileptic Disord 2009; 11 (3): 194-205 2.Blümcke et al. The clinicopathologic spectrum of focal cortical dysplasias: A consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission. Epilepsia, 52(1):158–174, 2011

8. Imaging findings of FCD Type II 1,2 Extratemporal with predilection of frontal lobes, more common in children Transmantle sign: The white matter signal alterations taper towards the ventricle, reflecting the involvement of radial glial- neuronal bands Increased cortical thickness Pronounced blurring of the gray matter/white matter junction both on T1WI and T2WI (due to increase disturbance in cortical structures vs. FCD I) Increased subcortical white matter signal on T2WI and heavily T2W FLAIR Increased T2-signal within affected cortex is far more common in FCD type II than in FCD type I; the grey matter remains hypointense 1.Colombo et at. Imaging of malformations of cortical development. Epileptic Disord 2009; 11 (3): 194-205 2.Blümcke et al. The clinicopathologic spectrum of focal cortical dysplasias: A consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission. Epilepsia, 52(1):158–174, 2011

9. Imaging findings of FCD Type II 1,2 Decreased signal on T1W images, either 3D volumetric Gradient Echo T1W or heavily T1W Inversion Recovery (IR) images Abnormal cortical gyration and sulcation, better evaluated on 3D surface rendering Focal enlargement of the subarachnoid spaces seem to point at the dysplastic lesion In a number of cases, a much sharper demarcation between the cortex and the adjacent white matter may be found 1.Colombo et at. Imaging of malformations of cortical development. Epileptic Disord 2009; 11 (3): 194-205 2.Blümcke et al. The clinicopathologic spectrum of focal cortical dysplasias: A consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission. Epilepsia, 52(1):158–174, 2011

10. Detailed analysis of following structures by imaging: Increased cortical thickness Blurring of the grey/white matter junction with disappearance of subcortical white matter digitations White matter signal abnormalities with or without extension all throughout the cortical mantle (the transmantle sign) Focal enlargement of subarachnoid space adjacent to cortical anomaly Grey and/or white matter signal changes Abnormal gyral/sulcal patterns Focal and/or lobar hypoplasia/atrophy The Checklist

11. Detailed analysis of the following structures: Increased cortical thickness

12. Detailed analysis of the following structures: Blurring of the grey/white matter junction with disappearance of subcortical white matter digitations

13. Detailed analysis of the following structures: White matter signal abnormalities with or without extension all throughout the cortical mantle (the transmantle sign)

14. Detailed analysis of the following structures: Focal enlargement of the subarachnoid spaces

15. Grey and/or white matter signal changes Detailed analysis of the following structures:

16. Abnormal gyral/sulcal patterns

17. Detailed analysis of the following structures: Focal and/or lobar hypoplasia/atrophy

18. Caveats in analysis: Cortical thickening should only be reported if the cortex appears thick on both T1W and T2W sequences that are windowed for high levels of contrast, in at least two planes Blurring and cortical thickness should be evaluated specifically and individually on: T2WI 3D volumetric Gradient Echo T1WI Heavily T1W Inversion Recovery (IR) images

19. Analysis in infants 1 : In FCD, the subcortical white matter may sometimes be isointense to cortex (and, therefore, appear as blurring or thick cortex) on T1WI but will look hyperintense to cortex on T2WI, delineating the junction with the cortex and showing true cortical thickness, THUS YOUR T2 SEQUENCE IS THE MOST IMPORTANT Before 6 months of age, the hypointensity on T2W images of the cortical dysplasia is very clear in contrast to the hyperintensity of the unmyelinated white matter If the first MR study is obtained between ages of 6 and 18 months, a second scan will be required when myelination is largely completed (after the age of 30 months) 1.Colombo et at. Imaging of malformations of cortical development. Epileptic Disord 2009; 11 (3): 194-205

20. FINDINGS/DISCUSSION

21. CASES

22. Case #1 Where are the findings? Have you used your checklist? √ Cortical thickening √ Blurring of grey/white matter junction

23. 17 y/o with intractable dominant motor cortical seizures No seizures since surgery 5/2008 Continues on Trileptal at 600 mg twice daily Case #1 Subtype of FCD not reported / not available

24. Case #2 Where are the findings? Have you used your checklist? √ Cortical thickening √ Blurring of grey/white matter junction

25. 13 y/o with medically refractory epilepsy No seizures since surgery 7/2009 On Dilantin, last active 10/2010 Case #2

26. Case #3 Where are the findings? Have you used your checklist? √ Cortical thickening √ Blurring of grey/white matter junction √ Abnormal white matter signal

27. 10 y/o with medically intractable seizures No seizures since surgery 10/2007 Weaned off Lamictal 2010 Case #3

28. Case #4 Where are the findings? Have you used your checklist? √ Cortical thickening √ Blurring of grey/white matter junction √ Prominent subarachnoid space

29. 11 y/o with seizures refractory to medical treatment No seizures since surgery 6/2008 Off meds since 9/2009 Case #4

30. Case #5 Where are the findings? Have you used your checklist? √ Cortical thickening √ Blurring of grey/white matter junction

31. Case #5 2 y/o with intractable seizures, surgery on 7/2013 Since surgery has had a new type of seizure involving his arms going up and who body stiffening without eye deviation Repeat MRI showed residual FCD

32. Case #6 √ Blurring of grey/white matter junction Where are the findings? Have you used your checklist?

33. 19 month old with intractable seizures, surgery on 3/2014 No seizures since surgery Weaning off Lamictal Case #6

34. Case #7 Where are the findings? Have you used your checklist? √ Cortical thickening √ Blurring of grey/white matter junction √ Abnormal grey and white matter signal

35. 5y/o with medically intractable epilepsy Improved, but persistent seizures after surgery 10/08 On Keppra, Lamictal, Strattera and Valium Case #7

36. Case #8 Where are the findings? Have you used your checklist? √ Abnormal gyral pattern √ Blurring of grey/white matter junction √ Abnormal grey and white matter signal √ Prominent subarachnoid space

37. 16 y/o, unfortunately, lost to follow-up, no clinical history post-op available Case #8 Subtype of FCD not reported / not available

38. Case #9 Where are the findings? Have you used your checklist? √ Blurring of grey/white matter junction

39. 17 y/o with medically intractable epilepsy Worsening seizures since surgery on 12/12, considering NeuroPace treatment Case #9 Subtype of FCD not reported / not available

40. Case #10 Where are the findings? Have you used your checklist? √ Cortical thickening √ Blurring of grey/white matter junction √ Abnormal white matter signal

41. 9 y/o with medically intractable seizures, surgery on 6/2011 Seizure-free and off Valproic Acid Case #10

42. Surgical outcomes Several articles have been published about patient outcomes after surgical removal of suspected epileptic foci, a few specifically relating to FCD Articles report approximately 70% success rate in achieving seizure-free status (Engle Epilepsy Outcome Scale I). Most failures are associated with incomplete resection of seizure foci, either due to technique or nearness to critical functional areas 3 3. Cohen-Gadol, AA, et al. "Long-term outcome after epilepsy surgery for focal cortical dysplasia." Journal of neurosurgery 101.1 (2004): 55-65.

43. SUMMARY

44. In summary Focal cortical dysplasias can be hard to identify on imaging, thus USE THE CHECKLIST to help guide you in the identification of these lesions Since surgical treatment is currently the same regardless of FCD type, correct imaging identification of isolated FCD on imaging is more important than histologic classification for surgical planning and decision-making Correlation with functional imaging, such as PET- Brain or SPECT-Brain is very useful in localizing these lesions

45. References Colombo N et al. Imaging of malformations of cortical development. Epileptic Disord 2009: 11(3): 194-205 Blümcke et al. The clinicopathologic spectrum of focal cortical dysplasias: A consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission 1. Epilepsia 2011: 52(1), 158-174 Cohen-Gadol AA, et al. "Long-term outcome after epilepsy surgery for focal cortical dysplasia." Journal of Neurosurgery” (2004): 101.1, 55-65

46. Thank you for your attention!