Disclosures 2/10/2017. RAIN 2017 Difficult Cases Session. Patient MC, Original Diagnosis, 9/2006. MRI 9/5/06, pre-op

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1 Disclosures RAIN 2017 Difficult Cases Session Clinical trials research funding support from: Novartis Genentech/Roche Merck NEUROLOGY AND NEUROLOGICAL SURGERY Jennifer L. Clarke, MD, MPH Associate Professor Division of Neuro-oncology Feb 10, 2017 Patient MC, Original Diagnosis, 9/2006 MRI 9/5/06, pre-op 49 yo RH man who presented in July 2006 with temporal lobe seizures (episodic smell/taste abnormalities and auditory hallucinations) Treated with DPH, biopsy locally with path called anaplastic astrocytoma, referred to UCSF Neurosurgery Clear growth between July scan and Sept pre-op scan; surgical resection w/ awake language mapping recommended 3 4 1

2 MRI 9/7/06, post-op MRI 9/7/06, post-op T1 pre-gad T1 post-gad T1 pre-gad T1 post-gad 5 6 Patient MC, Initial Treatment MRI 11/20/06, post-rt Aggressive resection achieved, small amount of residual tissue Pathology read as glioblastoma, WHO grade IV, based on presence of necrosis and microvascular proliferation Patient enrolled on a phase 1 clinical trial adding an experimental drug, enzastaurin, to standard post-op treatment with radiation and temozolomide 7 8 2

3 MRI 7/11/08, on treatment Patient MC, Initial Treatment, cont He remained on adjuvant treatment with temozolomide and enzastaurin (study drug) for a total of 45 cycles, eventually voluntarily stopping in July 2010 Seizures were well-controlled on levetiracetam (LEV) 500 mg BID; he would have occasional transient dizzy spells of unclear significance, without other associated symptoms 9 10 Patient MC, History, cont. I saw him in Jan 2014, with stable imaging. At that time, he reported no seizures, but he noted that his speech would worsen a bit with fatigue A few weeks later I received a garbled message from him: My mouth is walking with wrong often. Very like I've been using during our visit. I'm walking distributed it walking. Is this the fits? I spoke with him by phone, and he reported several minute episodes of acute-onset aphasia and difficulty reading/writing since his clinic visit. No associated headache, focal weakness, or alteration in sensorium (as had previously been associated with his seizures) No missed doses of levetiracetam LEV increased to 750 mg BID; routine EEG showed no epileptiform activity

4 4/2014: Aphasia episodes continued, perhaps less frequent with increased LEV dose. Discussed further increase in dose to 1000 mg BID but patient didn t wish to. MRI stable. Over next few months, episodes worsened in frequency and severity 5 days PTA, he began to have frequent episodes of aphasia with associated rising epigastric sensation, sounds, and dyscognitive symptoms that eventually merged into continuous symptoms 13 He presented to the UCSF ER on 10/20/14. Exam at that time was fully intact except: Mental Status: alert, oriented; halting speech with frequent semantic and phonemic paraphasias, word-finding difficulties, Able to name key, chair, glove but not hammock, garbled nonsensical speech when attempting to read phrases, intact comprehension to spoken language; memory intact to the details of the history He was admitted, EEG monitoring placed: This continuous video EEG is abnormal due to very frequent clinical and subclinical focal seizures consistent with focal status epilepticus. 14 Seizures were very difficult to control; over 2 days the following med changes were made: LEV re-load, maint increased to 1500 mg BID DPH loaded, maint started at 300 mg QHS Topiramate started at 200 mg BID MRI done 10/22/14: MRI 10/22/

5 Audience Question What are we seeing on this MRI? A. Tumor progression B. Post-ictal changes C. A combination of both tumor and post-ictal changes T u m o r p r o g r e s s i o n 13% P o s t - i c t a l c h a n g e s 10% A c o m b i n a t i o n o f b o t h... 77% Dexamethasone 4 mg BID started Seizures controlled Patient discharged 10/23/14, steroid taper initiated on 11/3/14 Short-interval MRI done on 11/10/14; no further seizures and clinical status as follows: Speech is subfluent with word-finding difficulty, but with intact repetition and comprehension and only 1 word missed on naming MRI 11/10/14 Successfully tapered off steroids over 2 months w/o further seizures He remains on all 3 AEDs New baseline for speech, slightly less fluent/more word-finding trouble than prior baseline Imaging remains stable without evidence of recurrence as of 12/2016, 2 years later

6 Peri-ictal Imaging Abnormalities Ref: Rheims S, Ricard D, van den Bent M, et al: Peri-ictal pseudoprogression in patients with brain tumor. Neuro-Oncology 13: , 2011 Peri-ictal Imaging Abnormalities Retrospective review of 10 cases in pts with stable, treated tumors demonstrated a pattern of imaging findings: Focal cortical and/or leptomeningeal enhancing lesions, c/w BBB disruption T2W imaging and DWI may be variable Perfusion may be elevated (done/elevated in 2 pts) Prolonged seizure activity, even if focal, can lead to significant imaging changes Thank you! Half Dome, Yosemite National Park, California, USA 6