1. Practice of Neuropathology Overview and Selected Cases Marc G. Reyes, M.D.

2. Diagnostic Neuropathology Principles and Methods Clinical findings—history, neurological examination and clinical course Clinical laboratory tests—MRI, CT, Angiograms, EEG Neuropathological examination---brain autopsy, brain, muscle and nerve biopsy Is there a neurological lesion? If so where is it and what is it?

3. Case 1 Clinicopathological Correlation Transient Ischemic Attacks (TIA’s) Deficits resolve without residuals within minutes to hours. Believed to be a precursor of completed strokes In the 50’s and 60’s thought to be thromboembolic but not not clear whether or not infarctions were present. In the late 70’s to the present, reduced flow from atherosclerotic narrowing of carotid artery considered to be the main cause— treatable surgically. Still no emphasis on accompanying infarctions In the 2000’s, imaging (CT and MR) have shown ~30% with infarctions which may be clinically silent or may have become asymptomatic; symptoms may recur with repeated ischemia to the same area

4. Case 2 Neuropathological Findings Vague whorling and storiform pattern with rare large hyperchromatic nuclei

5. Case 2 Neuropathological Findings Cell clusters separated by small blood vessels with recent hemorrhage

6. Case 2 Neuropathological Diagnosis Description Highly vascular ventricular neoplasm composed of clusters of spindled cells forming vague syncitial, whorled and storiform clusters separated by thin walled blood vessels. The neoplasm showed recent and old hemorrhage. There were scattered tumor cells with large probably degenerating nuclei but no mitosis, necrosis or other histologic signs of malignancy. Diagnosis Meningioma, angiomatous type, ventricular, with hemorrhage, into the ventricles and left frontal lobe

7. Case 2 Final Thoughts Meningiomas arise from leptomeningeal cells and pial remnants in choroid plexus and ependyma—”cap” cells, fibroblasts and blood vessels. Arachnoidal cap cells originate from neural crest or mesenchyme. Almost all meningiomas are benign. Many arise from the cap cells—often referred to as meningothelial meningiomas with syncitial and/or whorling patterns. Others are highly vascular, the so-called angioblastic meningiomas. Some arising from blood vessels, e.g. hemangiopericytomas of the meninges are identical to their soft tissue counterparts. Many of these tumors show histologic atypia and are clinically more aggressive with tendency to recur or metastasize.

8. Case 2 Final Thoughts Meningiomas--~20 to 25% of brain tumors, commonly located in the cerebral convexities, base of the brain, spinal canal and rarely intraventricular. Clinical presentation—slow growth may not become symptomatic until very large, some found incidentally at autopsy Signs and symptoms from compression and displacement of brain resulting in cranial nerve palsies and focal motor and sensory deficits. Seizures, increased intracranial pressure and rarely dementia in others.

9. Case 3 Clinical Points for Discussion Basal subarachnoid hemorrhage Usually from ruptured berry aneurysm of the circle of Willis Presents with headache, stiff neck and loss of consciousness May extend into the ventricles and cause dilatation and coma Vascular anomaly is less common cause Traumatic tear of vertebral artery is rare cause, usually from hyperextension injury of the neck.

10. Case 3 Neuropathological Findings Cerebral edema with scant subarachnoid hemorrhage of cerebral convexities

11. Case 3 Neuropathological Findings Sections of the left cerebellar hemisphere showing recent hemorrhage of the inferior semilunar lobule. The hemorrhage in the cortex and subcortical white matter compressed the middle cerebellar peduncle and 4 th ventricle. The small amount of blood in the 4 th ventricle came from retrograde flow from basal subarachnoid hemorrhage and was not a direct extension of the cerebellar hemorrhage.