Putting it all Together-Case Based Scenarios

1. Putting it all Together-Case Based Scenarios Ryan Hakimi, DO, MS Associate Professor Director, Critical Care Neurology Emmaculate Fields, APRN-CNP Clinical Instructor Department of Neurology The University of Oklahoma Health Sciences Center

2. DISCLOSURES • FINANCIAL DISCLOSURE • Nothing to disclose • UNLABELED/UNAPPROVED USES DISCLOSURE • Nothing to disclose • Some of the slides have been adapted from teaching materials used at the University of Oklahoma Health Sciences Center

3. LEARNING OBJECTIVES Upon completion of this course, participants will be able to: • Apply their knowledge of ischemic stroke imaging to improve patient care • Describe the significance of neuroimaging in the management of patients presenting with hemorrhagic stroke and use neuroimaging to guide further management • Distinguish the common neuroimaging findings in patients with brain tumors and multiple sclerosis

4. Multi-modal Neuroimaging modalities for Case Based Learning 25 minutes each. • Case 1: Acute ischemic stroke • Case 2: Intracranial hemorrhage • Case 3: Aneurysmal subarachnoid hemorrhage • Case 4: Glioblastoma multiforme • Case 5: Demyelinating disease • Bonus Cases

5. Case study 1 : Acute ischemic stroke • HPI: 48 y/o female with no known pmhx who presents with right hemiplegia, neglect, dysarthria • Last known well 12 hours ago • VS: 98/60, HR 82, RR 17, Afebrile, spo2 100% on RA • Vascular risk factors: None • Medications: None • Surgical hx: Non contributory • Family hx: Non contributory • Labs: chem- wnl, plt 200k, INR 1.0 • EKG: NSR • CT w/o contrast: Look for early ischemia/infarctions, hemorrhage

6. Multi-modal neuroimaging-Initial • CT head w/o contrast- Looking for ischemic changes, hyperdense MCA, hyperdense basilar, hyperdense ICA-If at all possible don’t let the pt leave the scanner to get the CTA. • CTA Head- Looking for dissection, atherosclerosis, extracranial occlusion , thrombosis, clot burden, collateral vessels • MRI- Some places obtain them prior to intervention • Treat ischemic strokes with IV lytics –tPA • Endovascular therapy for clot retrieval, IA tPA, dissection repair

7. Further Workup Normal flow RMCA Absent flow LMCA • Initial CT head may indicate the need for further testing such as echocardiography to assess for hypertensive heart disease or endocarditis, body imaging in the search for a primary malignancy, etc. • Holter monitoring for arrhythmia • MRA if CTA not obtained • TCD’S for emboli detection if suspicious that pt is still throwing clots/PFO • Carotid ultrasound – for stenosis • Secondary stroke prevention: ASA/Plavix, anticoagulation, statin

8. MRA axial view MRI DWI R AChA Territory • Common: • hemiparesis (contra, F/A/L) • hemisensory loss (contra, F/A/L) • Less common • hemianopsia • aphasia (L) • neglect (R) • other lacunar syndromes P Infarction in anterior choroidal artery (AChA) territory in subcortical white matter, in this case, posterior limb internal capsule; the AChA is a very small artery not usually seen on MRA or even catheter angiography that originates from the distal ICA or, less commonly, the proximal MCA; because it is small and comes off the ICA at a right angle, AChA-territory infarctions are usually due to small-artery disease, though complete AChA-territory infarctions may be due to embolism. ANTERIOR CHOROIDAL ARTERY (AChA)

9. MRI DWI MRA coronal view ACUTE BRAINSTEM INFARCTIONPOSTERIOR INFERIOR CEREBELLAR ARTERY (PICA) TERRITORY INFARCTION • Crossed pin sensory loss (ipsi face, contra body) • Vertigo, nausea • Dysphagia, hoarseness • Horner syndrome (ipsi) • Hemi-ataxia (ipsi) Acute infarction in PICA territory involving lateral medulla; PICA occlusions are nearly always due to embolism, vertebral artery atherothromboembolism more often than cardioembolism; called lateral medullary syndrome or Wallenburg syndrome

10. Case study 2: Intracranial hemorrhage due to arterial hypertensive vasculopathy • HPI: 55 y/o male with pmhx of HTN who presents with sudden onsent of left hemiplegia • Last known well 2 hours ago • VS: 198/110, HR 70, RR 18, Afebrile, spo2 93% on RA • Vascular risk factors: HTN • Medications: Lisinopril-non compliant • Surgical hx: Non contributory • Family hx: Non contributory • Labs: chem- wnl, plt 200k, INR 1.0 • EKG: NSR • CT w/o contrast: Look for early ischemia/infarctions, hemorrhage, etc. Left basal ganglia ICH

11. Multi-modal neuroimaging-Initial • CT head w/o contrast- Basal ganglia hemorhage, if at all possible don’t let the pt leave the scanner to get the CTA • CTA Head- Looking for vascular etiology-AVM, dural fistula, spot sign (suggests active hemorrhage) • MRI/MRA- for vascular etiology if CTA can’t be obtained

12. Use of CTA for hemorrhagic stroke • One-third of ICH patients will have hematoma expansion on follow up head CT within the first three hours of symptom onset • The use of CTA head or a contrast enhanced head CT (when CTA is not available) can allow for earlier identification patients via the “spot sign” wherein contrast is identified within the hemorrhage suggesting active bleeding. • A CTA head can further identify underlying vascular lesions that would then guide therapy and influence the patient’s outcome.

13. CTA spot sign An 84 year-old man was transferred to our hospital from a referring facility for a right frontal ICH. He was initially brought in to the referring ED for left-sided facial droop and dysarthria. A head CT was obtained (Image 1). Patient became unconscious immediately after the initial head CT and was intubated. A stat head CTA was obtained which showed extension of the ICH and a spot sign suggesting active hemorrhage (Image 2). He was then transferred to our hospital. Exam on arrival revealed a GCS of 6T (E1, V1t, M4 ). A repeat head CT a few hours later showed further expansion of the ICH and significant midline shift (Image 3). Later, the family chose to pursue comfort care measures . Image 3 Image 1 Image 2

14. Neuroimaging Guiding Management • Identifying pattern of blood on the initial head CT can guide subsequent neuroimaging. • This may include the need for a repeat head CT after a few hours to assess for worsening hemorrhage, edema, or midline shift; need for a CTA and/or DSA in case of ICH from suspected AVM or AVF; need for MRI brain without contrast in case of ICH from suspected hemorrhagic transformation of ischemic stroke or ICH from cerebral amyloid angiopathy; need for MRI brain with contrast when ICH from suspected tumor or infectious process; and need for an MR or CT venogram in case of ICH suspected from CVT. • Discovery of an ICH with intraventricular extension and resultant obstructive hydrocephalus in a comatose or severely encephalopathic patient may lead to placement of an external ventricular drain with dramatic improvement in the patient’s clinical exam at times. • Findings suggestive of elevated intracranial pressure may indicate the need for hyperventilation and hyperosmolar therapy.

15. Image 1 is a non-contrast head CT image of a 66 year-old man who had been on chronic anti-coagulation with Coumadin secondary to aortic valve replacement and presented with intraventricular hemorrhage. INR was 2.4 on presentation. He was administered intravenous vitamin K and prothrombin complex concentrate to reverse the anti-coagulation. Further work-up including CT head angiogram, MRI brain, and digital subtraction angiography did not reveal any underlying abnormality (primary intraventricular hemorrhage). Images 2, 3, and 4 are of a 26 year old man who brought in to our hospital when he collapsed after bowel movement. Non-contrast CT head showed intraventricular hemorrhage (Images 2 & 3). Image 4 is the DSA of the left vertebral artery that revealed a dissecting aneurysm at the left anterior inferior cerebellar artery (secondary intraventricular hemorrhage). Examples of primary and secondary intraventricular hemorrhage Image 1 Image 2 Image 3 Image 4

16. Case 3: Aneurysmal Subarachnoid hemorrhage • A 55 y/o female with pmhx of CAD s/p recent LAD stents placement 3 months ago on Plavix, htn, smoking who presents today via EMS complaining of the worst headache of her life. • VS: 164/92, HR 120, RR 10, Afebrile, spo2 90% on RA • Vascular risk factors: HTN, CAD s/p stent placement • Medications: coreg/plavix • Surgical hx: as above • Family hx: Non contributory • Labs: chem- wnl, plt 90k, INR 1.0, wbc 20k • EKG: NSR • CT w/o contrast: SAH –basal cisterns and IVH-4th ventricles

17. Multi-modal neuroimaging-Initial • CT head w/o contrast-SAH with IVH,if at all possible don’t let the pt leave the scanner to get the CTA. • CTA Head- Looking for vascular etiology- Aneurysm present • MRI/MRA- for vascular etiology if CTA can’t be obtained • Endovascular treatment- Conventional angiogram, aneurysm coiled • TCD- for cerebral vasospasm monitoring • Surgical treatment: as needed

18. Imaging Circle of willis Basilar tip aneurysm

19. Treatment options Coiling (3:1 ratio of dome to neck dimension is needed) Clipping (anterior circulation lesions)

20. Subarachnoid hemorrhage secondary to a ruptured saccular aneurysm46-year-old woman with medical history of untreated hypertension was admitted to our hospital for abrupt onset severe headache that persisted for three days (Hunt & Hess grade 2). A non-contrast CT head showed small subarachnoid hemorrhage in the prepontine cistern (Image 1; Fisher grade 1). CTA head was next obtained which showed a basilar apex aneurysm adjacent to the area of hemorrhage (Image 2). The aneurysm was emergently treated by balloon-assisted coiling. Image 3 shows the basilarapex aneurysm on DSA. Image 4 depicts the DSA 3-D reconstruction of theaneurysm. Image 5 is the final results of the acutely performed balloon-assistedcoiling (notice the contrast filling at the base of the aneurysm suggestive smallresidual aneurysm). The patient was brought back few months later andunderwent Y-stent remodeling and further coiling that resulted in completeradiographic occlusion of the aneurysm (Image 6; note the stent tines in the bilateral posterior cerebral and basilar arteries). Image 6 Image 4 Image 5 Image 2 Image 3 Image 1

21. Subarachnoid hemorrhage secondary to a ruptured blister aneurysm76-year-old man with a history of poorly controlled diabetes, significant coronary artery disease, and hypertension presented to our hospital with acute onset headache , encephalopathy, and decreased level of consciousness. A CT head showed diffuse extensive subarachnoid hemorrhage (Image 1; Fisher grade 3)An external ventricular drain was emergently placed without any improvement in his clinical exam. A CTA head was next obtained which was suggestive of a mid basilar artery aneurysm. Emergent DSA was performed which confirmed a blister aneurysm at the mid basilar artery, above the origin of the right anterior inferior cerebellar artery (Image 2). The aneurysm was acutely treated endovascularly by deploying two overlapping intracranial stents across the lesion in the hope of slowing the flow to the aneurysm. However, no stagnation of flow in the aneurysm was noted. The patient later died few days later from rehemorrhage from this aneurysm. Image 2 Image 1

22. Subarachnoid hemorrhage (SAH) secondary to intracranial dissection47-year-old man with history of type-II diabetes, hypertension, and coronary artery disease, was transferred to our hospital for further management of SAH. Per patient’s wife, the patient was complaining of constipation, went to bathroom, and felt a “pop” in his head while having bowel movement. This was followed by severe headache and generalized weakness. He was taken to the referring facility by EMS and declined further en route. A non-contrast head CT revealed SAH (Image 1, Fisher grade 4). Upon arrival at our hospital, neurological exam revealed a GCS of 3T. A stat head CTA was obtained but did not reveal an underlying cause of SAH (Image 2). An external ventricular drain was placed by the Neurosurgery Team. A DSA was then performed. Image 3 demonstrates DSA from the left vertebral artery that revealed an intracranial dissection involving the right posterior cerebral artery which was confirmed on superselective angiography of the right posterior cerebral artery (Image 4) as well as three dimension cine rotational angiography (Images 5, circled segment). No definitive treatment of intracranial dissection could be performed. Patient had a complicated ICU course over next few days which included a non ST-elevation myocardial infarction, continued increased intracranial pressure, and multiple bilateral acute ischemic strokes secondary to cardio-embolism. He was later made comfort care per family wishes and expired shortly thereafter. Image 1 Image 3 Image 5 Image 4 Image 2

23. Case 4: Brain tumors • Location • Supratentorial- mostly adults • Infrantentorial- mosty kids, small space to grow • Intra-axial (from the brain), extra-axial (from the skull or meninges) • Age of patient • Imaging modalities: CT/MRI with contrast to r/o infectious etiology

24. FLAIR & T2: Lesions are typically hyperintense Usually w/ extensive vasogenic edema due to disruption of blood-brain barrier Often w/ central necrosis FLAIR Image FLAIR MRI of BRAIN TUMOR Glioblastoma Multiforme Pt Z

25. T1-weighted MR without contrast: Images are typically hypointense If necrosis occurs, there may be areas of  or  signal (blood at different stages) w/in the lesion T1-weighted MR with gadolinium contrast: There is irregular enhancement (due to disruption of blood-brain barrier) T1 W/ & W/O CONTRAST MRI of BRAIN TUMOR Glioblastoma Multiforme Pt Z T1 without gadolinium contrast T1 with gadolinium contrast

26. Case 5: Demyelinating Disease • The most common demyelinating disease is multiple sclerosis (MS) • MRI brain is the imaging of choice in suspected cases of MS • MRI helps identify acute (inflammatory) vs chronic lesions • Helps delineate disease burden and guide management

27. Multiple hyperintense lesions in periventricular white matter Lesions typically ovular in shape w/ long axis perpendicular to ventricles Note: Lesions seen best on FLAIR or T2- weighted images Axial FLAIR images of a Pt w/ MS FLAIR Axial MRI of MULTIPLE SCLEROSIS WM lesions Ovular lesions

28. FLAIR Sagital MRI of MULTIPLE SCLEROSIS • On sagittal images, the ovular periventricular lesions have the appearance of fingers projecting from the ventricles and are often called “Dawson’s fingers” Dawson’s fingers

29. T1 Axial C - T1 Axial C + T1 Sagittal C - T1 Sagittal C + MULTIPLE SCLEROSIST1 W/ & W/O CONTRAST • New MS lesions (plaques) enhance with gadolinium contrast (due to blood-brain-barrier disruption), seen best on T1-weighted images with contrast, compared to T1 without contrast New lesion enhancing w/ contrast

30. Hemorrhagic lesions d/t CNS infections and neoplasms • Most common primary CNS infection associated with ICH reported in the literature is herpes encephalitis. • Presence of bacterial endocarditis and HIV are also known risk factors. • ICH can also be secondary to an underlying brain tumor, either a primary brain tumor or a metastatic brain tumor. • Overall, primary brain tumors are reported have a lower rate of ICH as compared to brain metastases • When excluding pituitary adenoma, large retrospective studies have identified hemorrhage in 14.6% of autopsy cases of patients with brain tumors, with 5.4% being macroscopic ( 43). Also, amongst the primary brain tumors excluding pituitary adenomas, pilocytic astrocytoma has the highest hemorrhage rates. The primary determinant of hemorrhagic brain metastases is the underlying tumor pathology. Thyroid papillary carcinomas, hepatocellular carcinomas, melanoma, and renal cell carcinoma have the highest propensity for hemorrhage • Cerebral edema that is disproportionate to the size of ICH on non-contrast head CT is usually indicative of an underlying neoplastic or infectious process.

31. Hemorrhagic lesions d/t CNS infections and neoplasms • Differentiating infectious from a neoplastic process based on neuroimaging findings requires knowledge of the clinical history. • Findings suggestive of an underlying infectious process include: • Hypointense T2 rim around a lesion, leptomeningeal enhancement, the presence of diffusion restriction suggesting a cerebral abscess, presence of subdural empyema, or the presence of mycotic aneurysm (aneurysm arising from infection of the arterial wall). • Most brain tumors are iso-hypointense on T1 and hyperintense on T2 MRI sequences. • Meningiomas are usually isointense on both T 1 and T2 MRI sequences. • The cystic-necrotic areas usually associated with malignant tumor such as glioblastoma multiforme (GBM) are markedly hypointense on T1 and hyperintense on T2. • On contrast enhanced MRI images, low-grade tumors do not exhibit contrast enhancement, while high-grade tumors exhibit significant enhancement because of the blood-brain barrier disruption. DSA can sometimes exhibit characteristic tumor blush in case of highly vascular tumors such as hemangioblastomas

32. Intracranial hemorrhage secondary metastatic brain disease85 year old man with a past medical history of hypertension, heart disease, and "mini-strokes" was admitted to our stroke service following an intracerebral hemorrhage manifested by a transient episode of expressive aphasia. Head CT (Images 1 and 2)and MRI GRE (Images 3 and 4)images below show two distinct areas of hemorrhage, a large left frontal hemorrhage and a smaller right posterior temporal hemorrhage. There was heterogeneous hypointense/hyperintense T2/FLAIR (Images 5 and 6) signal and relatively hypointense T1 signal consistent with an acute hematoma while the post contrast images demonstrate contrast enhancement as seen in the images below. Due to the concern for a metastatic process, contrasted CT of the chest, abdomen, and pelvis, as well as PET CT were obtained. PET CT (Image 7)revealed diffuse metastatic disease with multiple lesions noted in the soft tissue, adrenal glands, lungs, and bones. Patient was later discharged to hospice. Image 1 Image 2 Image 7 Image 3 Image 5 Image 6 Image 4

33. NONCONTRAST CT SCAN: MASS LESION (TOXOPLASMOSIS ABSCESS) Abscess (vague ring) Mass effect (compressed ventricle) Mass effect (R-to-L shift = subfalcine herniation) Vasogenic edema (due to mass lesions, e.g., abscess, tumor; represents blood-brain barrier disruption; involves only white matter)

34. CONTRAST CT SCAN: MASS LESION (TOXOPLASMOSIS ABSCESS) Abscess (ring enhancement) Note that the mass lesion is more clearly defined (called “ring enhancement”). Enhancement with contrast is due to leakage of dye around the lesion and occurs as a result of blood-brain barrier disruption.

35. ICH secondary to cerebral venous thrombosis (CVT) • CVT is thrombosis of the venous sinuses and veins in the brain. • Cortical vein thrombosis refers to CVT involving only a small cortical vein as opposed to venous or lateral sinus thrombosis, which implies involvement of one of the large cerebral venous sinuses. • The appearance of the thrombus on MRI is time specific: • Isointense on T1 and hypointense on T2 in the acute phase • Hyperintense on T1 and T2 in the subacute phase • Isointense on T1 and hyperintense on T2 in the chronic phase ( 34) • MR and CT venography techniques can further aid in diagnosing CVT. • While the CT venogram involves administration of iodinated contrast medium, the MR venography can be performed without the need for contrast using 2D/3D time of flight as well as 2D and 3D phase contrast techniques.

36. T1 G+ T1 G- Sagittal Coronal Coronal CVT ON MRI WITH CONTRAST:DELTA SIGNT1 WITHOUT & WITH GADOLINIUM Parenchyma: often paramedian, gyral enhancement Sinovenous system: G- no flow; G+ delta/empty triangle sign

37. Intracranial hemorrhage secondary to cerebral venous thrombosis (CVT)29 year-old woman with a medical history of ulcerative colitis, on immunosuppressive therapy, presented to a referring hospital with new-onset persistent headaches. A non-contrast CT head at that time was unremarkable (Image 1). Two days later, she was brought in encephalopathic with the same persistent headache. A head CT with and without contrast was performed this time which now showed a large right temporo-parietal intracerebral hemorrhage with significant cerebral edema and a midline shift of 10 mm (Image 2). The contrast enhanced images also showed absence of contrast opacification at the right sigmoid sinus suggestive of CVT as the underlying cause of hemorrhage (Image 3). Patient was transferred to our hospital . A head MRV was also obtained that revealed extensive CVT involving the right internal jugular vein and the right transverse and sigmoid sinuses (Image 4). The patient was treated with heparin despite the presence of ICH (standard treatment). Significant right sided mastoiditis was also noted on the MRI images (Image 5) and hence ENT consult was obtained. It was felt that the mastoiditis was a consequence of CVT in this case rather than the cause, which is more often the case. Despite IV heparin and hypertonic therapy, the cerebral edema failed to improve and her clinical exam deteriorated leading to hemicraniectectomy. Her clinical condition gradually improved and she was later discharged to rehab. Image 3 Image 1 Image 2 Image 5 Image 4

38. References • Donato J, Campigotto F, Uhlmann EJ. Intracranial hemorrhage in patients with brain metastases treated with therapeutic enoxaparin: a matched cohort study. Blood 2015;126 (4): 494 – 499. • Hemphill, C. et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Stroke. 2015 Julyt 46(7): 2032-60 • Kondziolka, D, Bernstein M, Resch, L, et al. Significance of hemorrhage into brain tumors: clinicopathological study. J Neurosurg 1987;67:852-857 • Lieu AS, Hwang SL, Howng SL, et al. Brain tumors with hemorrhage. J Formos Med Assoc. 1999;98(5):365-7. • Sander Connolly, E. et al. Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage. Stroke 2012. 43: 1711-37. • Sheng-Jun Sun & Pei-Yi Gao & Bin-Bin Sui & Xin-Yi Hou & Yan Lin & Jing Xue & Ren-You Zhai. “Dynamic spot sign” on CT perfusion source images predicts haematoma expansion in acute intracerebral haemorrhage. Eur Radiol (2013) 23:1846–1854 • Wada R, Aviv RI, Fox AJ, et al. CT angiography “spot sign” predicts hematoma expansion in acute intracerebral hemorrhage. Stroke 2007;38:1257–1262.

39. QUESTIONS?