Neuropathology: Vascular Malformations

• Neuropathology involves the study of cerebrovascular disease, trauma, and CNS neoplasms.

Vascular Malformations

• Arteriovenous Malformations (AVMs) typically present in individuals aged 10-30.
• AVMs of the brain are associated with risk of hemorrhage which can be intracerebral or subarachnoid.
• Males are more affected than females at a ratio of 2:1.
• AVMs consist of abnormal collections of blood vessels interposed between feeding arteries and draining veins and can extend into brain parenchyma.
• AVMs are most common in the middle cerebral artery (MCA).
• On examination, AVMs can pulsatile AV shunting.
• Cavernous Malformations are linked to hemorrhage
• Cavernous Malformations are distended, loosely organized vascular channels with thin, collagenized walls lacking nervous tissue with the most common locations being the cerebellum, pons, and subcortical regions.
• Capillary Telangiectasias are microscopic foci of dilated and thinly walled vascular channels and most commonly occur in the Pons.
• Venous Angiomas/Varices are aggregates of ectatic venous channels.
• Foix-Alajouanine Disease involves angiodysgenetic necrotizing myelopathy-venous angiomatous malformation of spinal cord.

Cerebral Blood Flow

• The brain is supplied by 2 arteries: the internal carotid artery (ICA) and the vertebrobasilar system.

Cerebrovascular Disease

• Global Cerebral Ischemia is caused by low perfusion from atherosclerosis; acute decrease in blood flow (cardiogenic shock), chronic hypoxia (anemia), or repeated hypoglycemia (insulinoma).
• Ischemic Stroke leads to focal neuro deficit for >24 hours (TIA if <24 hr) and results in focal ischemia & liquefactive necrosis

Ischemic Stroke Types

• Thrombotic strokes arise from the rupture of an atherosclerotic plaque.
• Embolic strokes is most commonly from the heart i.e. A-fib and is carried to the Middle Cerebral Artery (MCA)
• Lacunar strokes are 2° to hyaline arteriolosclerosis (prolonged HTN).
• Intracerebral Hemorrhage are from Charcot-Bouchard microaneurysm of lenticulostriate vessel rupture caused by HTN (MC site: Basal Ganglia)
• Subarachnoid Hemorrhage causes worst headache ever, nuchal rigidity with xanthochromia from rupture of berry aneurysm, most commonly in the anterior communicating Artery in Circle of Willis

Cerebral Infarct Timeline:

• 0-6 hours post-infarct: No changes are observed.
• 12-24 hours: Red neurons are present on biopsy.
• 24-48 hours: Blood vessels become more prominent, and some neutrophils can be seen.
• 48 hours: Tissue becomes pale, soft, and swollen.
• 48-96 hours: Clusters of macrophages surround blood vessels.
• 2-10 days: Gelatinous and friable brain tissue is present.
• 10 days-3 weeks: Liquefactive necrosis & cavitation occurs.
• 2 weeks: Prominent astrocytosis ends in fibrillary gliosis.

Trauma

• Epidural Hematoma is associated with the fracture of the temporal bone with a rupture of the middle meningeal artery, lens-shaped on a CT with a lucid interval.
• Subdural Hematoma is caused by the tearing of bridging veins and the bleed is crescent-shaped, increasing the risk for elderly patients because of cerebral atrophy
• Herniation is a complication of brain swelling

Herniation types

• Tonsillar involves cerebellar tonsils that move into the foramen magnum causing cardiopulmonary arrest
• Subfalcine involves the cingulate gyrus under the falx cerebri causing anterior cerebral artery infarction
• Uncal involves the temporal lobe uncus under the tentorium cerebelli causing compression of CNIII, PCA, and rupture of paramedian artery

CNS Neoplasms

• Metastatic CNS neoplasms presents with multiple, well-circumscribed lesions at the gray-white junction and 50% of CNS neoplasms are metastatic.
• Common Metastatic sources of CNS neoplasms originate in the lung, breast, & kidney and 1° brain tumors rarely metastasize outside the CNS.
• Glioblastoma Multiforme are from astrocytes forming a butterfly lesion, with pseudopalisading necrosis.
• Glioblastoma Multiforme are GFAP positive and have a poor prognosis.
• Meningioma arises from arachnoid cells, being benign, causing seizures in addition to psammoma bodies.
• Schwannoma are from the schwann cells in CN VIII at the cerebellopontine angle, associated with hearing loss & tinnitus.
• Schwannoma are S100 positive, bilateral in Neurofibromatosis Type 2.
• Oligodendroglioma are from the Oligodendrocytes, can found in the frontal lobe, and are associated with seizures and cause a 'fried egg' appearance on biopsy and cause calcified white matter
• Pilocytic Astrocytoma are the MC CNS tumor in kids in the cerebellum with rosenthal fibers (eosinophilic processes of astrocytes + granular bodies) and are GFAP positive.
• Medulloblastoma are from neuroectoderm, and can be found in kids and contains small blue cells, with Homer-Wright rosettes, spreading via CSF with rapid growth.
• Ependymoma are from Ependymal cells, found in kids with 4th ventricle and are associated with hydrocephalus, perivascular pseudorosettes
• Craniopharyngioma are from Rathke's pouch remnants and are supratentorial, causing bitemporal hemianopsia in kids and display calcifications on scans

Pathology Department Slides

• Hypertensive Cerebrovascular Disease presents with lacunar infarcts (small, cavitary lesions), slit hemorrhages (rupture of penetrating vessels that cause small hemorrhages), hypertensive encephalopathy, and intracerebral hemorrhage.
• Risk factors associated with Intracerebral Hemorrhage include hypertension, amyloidosis, aneurysms, coagulation disorders, vasculitis, and vascular malformations/tumors.
• CAA: amyloidogenic peptides deposit in walls of small & medium vessels which causes vessels to weaken and risk hemorrhage and the E2/E4 allele increases the risk for repeat bleeding.
• Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare hereditary form of strokes (mutation in Notch 3 receptor) and dementia (basophilic, PAS-positive granular "brain sand" deposits)