Imaging Findings in Neuro Oncology Patients in the Emergency Setting

1. Imaging Findings in Neuro Oncology Patients in the Emergency Setting Thomas LoStracco MD, Rajiv Mangla MD, Douglas Drumsta MD, Thomas Folan MD, Jeevak Almast MD, Nimish Mohile MD ASNR 2015 Annual Meeting eEdE#: eEdE-48 Control#: 1061

2. We have no financial disclosures.

3. Introduction Neuro oncology patients require special consideration while being evaluated with imaging in the acute setting. Emphasis must not only be placed on identifying conspicuous findings, such as hemorrhage and hydrocephalus, but also searching for more subtle patterns, such as leptomeningeal enhancement, cortical swelling, and white matter changes, which are of especially important diagnostic significance in this patient population. Several examples of common and uncommon pathology that we have come across in the acute setting at our institution will be presented. This will include cases of treatment related complications. Focus will be placed on intracranial cases. Common pitfalls and mimics of malignant progression will also be discussed.

4. Introduction Neuro oncology patients often present with an extensive medical history, multiple symptoms, and multiple prior imaging studies for comparison. Interpreting imaging studies in these patient is complex. In many cases, a specific diagnosis cannot be reached, but rather the findings represent a combination of entities. This is further confounded by the fact nearly all of these patients have undergone or are currently receiving treatment. This process begins with selection of the appropriate imaging study and protocol for these patients, followed by considering pathologic entities that occur more commonly in patients with a history of a malignancy effecting the central nervous system.

5. 4 year-old with history of pinoblastoma status post gross total resection 2 years prior presenting with seizure, post ictal weakness and left gaze preference Follow up MR study Study 1 month prior Current study CT images demonstrate increasing hydrocephalus, as well as nodularity along the ependymal surface. These findings are confirmed on MR and are consistent with communicating hydrocephalus caused by leptomeningeal spread of tumor.

6. Leptomeningeal spread of tumor • Leptomeningeal spread may result in communicating hydrocephalus. • Clinical presentation is variable depending on how rapid the hydrocephalus develops. • Images demonstrate enlargement of the ventricles, most specifically, the third ventricle and temporal horns of the lateral ventricles. • Transependymal flow may be seen as increased T2 FLAIR signal on MR or hypoattenuation on CT within the periventricular region. • Thinning of the corpus callosum may also be present.

7. 64 year-old male with history of diffuse large B cell lymphoma presents with altered mental status CT scan demonstrates of the bilateral frontoparietal gyral hyperattenuation, which could be due to either leptomenigeal disease or hemorrhage. Therefore a contrast enhanced MR was performed, which showed extensive leptomeningeal spread. The GRE sequence demonstrates no evidence of hemorrhage.

8. 2 year-old female with history of desmoplastic infantile ganglioglioma presents with ptosis and dysconjugate gaze Images demonstrate post operative sequelae of left hemispherectomy, as well as bilateral involvement of cranial nerves II, III, and V.

9. Perineural spread of tumor leading to cranial nerve palsy • Perineural spread of tumor can be seen with enlargement and/or enhancement of the nerve itself or enlargement of the neural foramina. • T1 non fat suppressed sequence is essential to evaluate for obliteration of fat planes and a coronal sequence is essential for evaluation of foramina. • Key areas to evaluate include foramen ovale, foramen rotundum, Vidian’s Canal, gasserian ganglion, Meckel’s Cave, and the pterygopalatine fossa. Enlargement of the cavernous sinus may also be seen. • Pre and post contrast enhanced, high resolution MR images are idea for evaluating perineural spread at the skull base. Fat suppression is helpful on post contrast images, however, it may obscure neural foramina due to susceptibility artifact. • Adenoid cystic carcinoma, lymphoma, melanoma, and squamous cell carcinoma are tumors that have a propensity for perineural spread.

10. 66 year-old male with multiple myeloma with acute altered mental status • Post contrast image demonstrates leptomeningeal enhancement within the basilar cisterns. • Leptomeningeal enhancement is a nonspecific finding and analysis of the CSF may be necessary. • CSF analysis in this patient revealed cryptococcal antigen. • More severe cases of crytococcal meningitis demonstrate gelantinouspseudocysts and enlargement of the perivascular spaces.

11. Similar appearance of leptomeningeal spread 15 year-old male with no history of malignancy with 2 days history of severe headache. Images demonstrate diffuse dural enhancement. He was determined to have intracranial hypotension. His symptoms resolved 3 days after having a blood patch.

12. Dural Enhancement due to Intracranial Hypotension • This can mimic progression of tumor • Dural enhancement is nonspecific finding and may be focal or diffuse. • It can be seen with leptomeningeal carcinomatosis, meningitis, hemorrhage, post operative setting, encephalitis, granulomatous disease, following trauma, and following lumbar puncture. • Dural enhancement due to lumbar puncture is uncommon and is a diagnosis of exclusion

13. 60 year-old male with acute headache and transient right sided weakness CT angiography was performed and filling defects were noted within superior sagittal sinus, straight sinus, as well as within the vein of Galen.

14. MRI/MRV on same patient • The sagittal T1 weighted demonstrate loss of normal flow voids within the superior sagittal and straight sinuses, as well as within the vein of Galen and internal cerebral veins. • The 3D volume rendered MRV confirms these findings. Also note the restricted diffusion within the superior sagittal sinus.

15. Venous Sinus Thrombosis • Clinical presentation includes headache, focal neurological deficits, seizure • Malignancy causes a hypercoagulable state and predisposes patients to venous sinus thrombosis. • MR images demonstrate loss of normal flow voids and CT demonstrates filling defects within the dural venous sinuses. • Focal cortical cytotoxic or vasogenic edema, as well as decreased ADC may be present. Gyral, leptomeningeal, or venous cortical enhancement may also be seen. Hemorrhage is present in approximately a third of cases. • As opposed to arterial infarcts, changes may be reversible. • Thrombosis of deep cerebral veins (i.e. internal cerebral veins, vein of Galen, straight sinus) may manifest within thalamic edema.

16. Venous Sinus Thrombosis Protocol • CT or MR venography are most sensitive imaging tests. Although findings may be seen on CT angiography and conventional MR sequences. • 2D time of flight (TOF) venography is typically included in an MR venography protocol. • Phase contrast venography is less often used, as it operator dependent to encode velocity. • 2D TOF is favorable compared to 3D TOF, as it is less likely to be effected by saturation artifact. • Contrast enhanced venography is more favorable to TOF for depicting smaller vessels and is less effected by turbulent flow.

17. 64 year-old male with history of a right temporal GBM status post resection, as well as chemotherapy and radiation who presents with right sided vision loss and left homonymous hemianopsia Images demonstrate the lesion within the right hippocampus, as well as increased T2 FLAIR signal and diffusion restriction within the right optic tract and contrast enhancement at the optic chiasm, consistent with optic neuropathy. This may be related to radiation or bevacizumab treatment.

18. Diffusion restriction following treatment with bevacizumab Pretreatment Post treatment Images demonstrate a larger area of restricted diffusion and smaller region of enhancement following treatment of the glioblastoma. It is important to recognize that this may indicate favorable tumor response and not necessarily be interpreted as either acute stroke or tumor progression.

19. Bevacizumab (Avastin) • Monoclonal antibody that inhibits angiogenesis and is commonly used to treat recurrent glioblastoma. • In patients with recurrent glioma treated with bevacizumab, diffusion restriction can be a normal finding and may be a marker of favorable tumor response. • Additional potential adverse effects include hemorrhage, septal perforation, as well as hypertension, which can lead to posterior reversible encephalopathy syndrome (PRES).

20. Leukencephalopathy related to chemotherapy • Methotrexate causes has been associated with demyelination, white matter necrosis, loss of oligodendroglia, axonal swelling, microcysticencephalomalacia, ischemia, and atrophy. • Can result from intrathecal or intravenous administration. • Clinically may manifest as seizure or focal neurologic deficits. • Confluent areas of T2 FLAIR hyperintensity within the white matter. Diffusion restriction is an important finding, as the treatment course will need to be altered. It also may be reversible.

21. Radiation Treatment Complications • Acute- Occurs days to weeks post treatment. White matter edema is seen due to capillary permeability. • Early Delayed- 1 to 6 months post treatment. Periventricular T2 FLAIR white matter hyperintensity is present, which is reversible. • Late Delayed- At least 6 months post treatment. Diffuse white matter T2 FLAIR hyperintensity is present. U-fibers and corpus callosum are usually spared. Volume loss, calcifications, and radiation induced vascular malformation can also occur.

22. Radiation-Induced Brain Necrosis • Patient may present with nausea and memory loss. • Enhancing mass with surrounding edema, which makes it difficult to differentiate from tumor or abscess. • ADC values are increased. • MR spectroscopy demonstrates decreased NAA and increased lactate levels. • PET/CT will demonstrate hypometabolic activity within the lesion.

23. Radiation Necrosis Peripherally enhancing lesion within the left frontoparietal region with associated surrounding edema Cerebral blood volume is relatively low in the corresponding region

24. Additional example of radiation necrosis on 18F-FDG PET. Peripherally enhancing lesion within the right temporal lobe with no corresponding hypermetabolic activity on the PET image. This case is to illustrate the features but would not be seen in the acute setting.

25. 41 year-old male with acute left upper extremity weakness, ataxia, and facial droop. He has a history of an oligodenroglioma treated with radiation therapy two years prior to presentation.

26. SMART Syndrome (Stroke Like Migraine Attacks after Radiation Therapy) • Patients present years after radiation therapy. • Images demonstrate subtle asymmetric cortical thickening with T2 FLAIR hyperintensity, gyral enhancement, diffusion restriction. Cortical laminar necrosis can also be seen.

27. 31 year-old with history of medulloblastoma status post resection and radiation 20 years prior Images demonstrate a cavernous malformation within the left basal ganglia with hemosiderin and blood products of varying age mixed within it. Vascular malformations can develop in patients with a remote history of radiation. Patients may develop seizure or neurologic deficit from these lesions.

28. 17 year-old male with history of a left occipital glioblastoma status post resection and chemotherapy with new onset seizure Images at presentation demonstrate cortical swelling and T2 FLAIR hyperintenisty, as well as gyriform diffusion restriction within the region just cephalad to the resection cavity. Follow up imaging at 4 months demonstrate near complete resolution of the cortical swelling and no diffusion restriction within the same region without additional treatment. This suggests that the original findings are attributable to peri ictal pseudoprogression.

29. Peri-ictal Psuedoprogression • Pseudoprogression occurs in the subacute phase (most likely within the first 12 weeks) following radiation therapy. Increased size of the enhancing lesion is seen. It is due to inflammation and increased vascular permeability. • Transient focal cortical or leptomeningeal enhancing lesions in the setting of recurrent seizures can be mistaken for tumor recurrence.

30. Same patient demonstrating progressive radiation leukencephalopathy over the course of a year Nov 2013 Jan 2014 Nov 2014 Sep 2014 The changes are nonspecific and developed gradually over time, but they key to interpretation is the history. This patient received two separate 59.4 Gy courses of radiation therapy to the left occipital region, one in Oct 2010 and the second in Dec 2013.

31. 51 year-old female with history of a right frontal GBM status post resection undergoing chemo and radiation therapy 3 months prior Current study This case is an example of pseudoprogression. There is increased peripheral enhancement surrounding the tumor cavity in comparison to the study 3 months prior. However, the color CBV map shows decreased volume and the diffusion weighted image demonstrates no corresponding diffusion restriction. These findings are consistent with pseudoprogresson.

32. 70 year-old male with dysphagia, throat and right jaw pain. He has a history of squamous cell carcinoma of the tongue base status post resection and adjuvant radiation therapy completed one year prior to presentation Images demonstrate mixed lucent and sclerotic changes, as well as cortical erosion involving the right mandibular body and angle, consistent with osteoradionecrosis.

33. Osteoradionecrosis • Clinical presentation includes focal pain, swelling, dysphagia, fistula formation, and facial deformity. • Occurs approximately 1 to 3 years following radiation therapy. • Irradiated bone becomes devitalized following radiation therapy. The bone then becomes exposed through skin or mucosa.

34. 57 year-old female with history of GBM status post resection and receiving chemo and radiation therapy with enlarging skin wound at cranitomy site. Images demonstrate an enhancing extra axial fluid collection underlying the craniotomy site, which also demonstrates diffusion restriction. This has the appearance of a subdural empyema because of the restricted diffusion. However was determined to be hemorrhage, which should also be included in the differential.

35. 60 year-old male with a known pituitary macroademona presents with severe headache, hypertension, blurry vision, and respiratory distress Current study Study from 3 weeks prior Current study Images demonstrate decreased enhancement of the sellar mass in comparison to the prior, as well as new diffusion restriction within the mass. The patient was immediately taken to the OR for resection of the mass, which demonstrated an infarcted/necrotic pituitary adenoma.

36. Pituitary Apoplexy • Patient may clinically present with headache, opthalmoplegia, visual deficits, and altered mental status. • Prior radiation therapy is a risk factor. • May occur in preexisting adenoma. • May result from infarction or hemorrhage. • Diffusion restriction in cases of infarction. • Increased T1 signal in cases of hemorrhage.

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38. Correspondence Thomas LoStracco, MD 601 Elmwood Avenue Rochester, NY 14642 thomas_lostracco@urmc.rochester.edu Thank you