1. Differentiation of Peri-Ictal Pseudoprogression from Tumor Recurrence in a Patient with Treated Glioma: Value of Diffusion Weighted and Perfusion Imaging Dr Nader Zakhari and Dr Thanh Nguyen The Ottawa Hospital EE-07

2. Disclosure Dr Thanh Binh Nguyen has received an investigator-initiated research grant from Bayer Pharmaceutical

3. Purpose Peri-ictal pseudoprogression “PIPG” = Transient MR abnormalities in patients with brain tumor–related seizures that can incorrectly suggest tumor progression.

4. Purpose  To present the MR findings of PIPG including diffusion and perfusion imaging.  To differentiate PIPG from true tumor progression and avoid unnecessary interventions.

5. Case Report Presentation: August 2013  36 year-old man  Several simple and complex partial seizures with and without generalization.

6. Case Report History: February 2010  3 years earlier was diagnosed with left frontal anaplastic astrocytoma (III/IV)  Treatment (completed in 2010):  Surgery  Adjuvant radiation (60 Gy in 6 weeks)  Concomitant and adjuvant Temozolomide

7. Case Report Management: August 2013  Admission  MRI  Treatment: phenytoin and levetiracetam  No recurrence of seizures

8. Imaging findings Baseline post-operative MR (Sept. 2012) before presentation: Left frontal craniotomy Postoperative changes No diffusion restriction FLAIRDWI

9. Imaging findings T1 post-contrastCBV Postoperative changes No concerning enhancement No increased CBV Baseline post-operative MR (Sept. 2012) before presentation:

10. Imaging findings FLAIR Left frontal cortical swelling and hyperintensity MRI Aug. 2013 at presentation:

11. Imaging findings Left frontal cortical diffusion restriction DWI & ADC MRI Aug. 2013 at presentation:

12. Imaging findings T1 post- contrast T1 pre- contrast Enhancement Left frontal cortical/leptomeningeal enhancement MRI Aug. 2013 at presentation:

13. Imaging findings Dynamic Susceptibility Contrast Perfusion Cortical increased CBV in the left frontal region MRI Aug. 2013 at presentation:

14. Imaging findings FLAIR Resolution of swelling and signal abnormality MRI follow up Oct. 2013:

15. Imaging findings DWI and ADC MRI follow up Oct. 2013: Resolution of diffusion restriction

16. Imaging findings Enhancement MRI follow up Oct. 2013: T1 pre- contrast T1 post- contrast Resolution of leptomeningeal/cortical enhancement

17. Imaging findings Dynamic Susceptibility Contrast Perfusion Resolution of increased CBV in the left frontal region MRI follow up Oct. 2013:

18. Summary Peri-ictal pseudoprogression “PIPG” 1  Seizure-associated MR abnormalities in the surgical bed mimicking tumor progression  Rare entity ( <1%)  Survivors of glioma who have undergone radiotherapy  Average 10 years after treatment

19. Summary Previously described seizure-associated MRI abnormalities: 2-4  Cortical swelling  Cortical T2/FLAIR hyperintensity  Cortical diffusion restriction  Cortical and/or leptomeningeal enhancement  Increased cerebral blood volume (rCBV)

20. Summary Mechanism of seizure-associated MRI abnormalities: 2-5  metabolism of seizing neurons  Compensatory blood flow: perfusion  metabolism > blood flow:  Local tissue hypoxia diffusion restriction  Anaerobic metabolism: lactate & Pco2: vascular dilatation & leakiness disruption of blood brain barrier and enhancement

21. Summary PIPGTUMOR RECURRENCE DistributionPredominantly corticalPredominantly subcortical ReversibilityTransient & reversibleProgressive Diffusion restriction Cortical Not limited to the cortex Not a constant feature Contrast enhancement Cortical &/or focal leptomeningeal Predominantly subcortical Leptomeningeal enhancement more common diffuse PerfusionIncreased

22. References 1.Rheims S, Ricard D, van den Bent M et al. Peri-ictal pseudoprogression in patients with brain tumor. Neuro Oncol. Jul 2011; 13(7): 775–782 2.Rath JJG, Smits M, Ducray F, van den Bent M. J. Increased rCBV in status epilepticus. J Neurol 2012;259:1746–1748 3.Kim JA, Chung JI, Yoon PH et al. Transient MR Signal Changes in Patients with Generalized Tonicoclonic Seizure or Status Epilepticus: Periictal Diffusion-weighted Imaging. AJNR Am J Neuroradiol 2001; 22:1149–1160. 4.Szabo K, Poepel A, Pohlmann-Eden B et al. Diffusion-weighted and perfusion MRI demonstrates parenchymal changes in complex partial status epilepticus. Brain (2005), 128, 1369–1376. 5.Canasa N, Breiac P, Soares P et al. The electroclinical- imagiological spectrum and long-term outcome of transient periictal MRI abnormalities. Epilepsy Research 2010;91:240—252

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