Vascular diseases of the central nervous system

Prof. Isidro Ferrer, Institut Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, CIBERNED, Hospitalet de LLobregat; Spain

Diseases of the blood vessels

1. Atherosclerosis 2. Hypertensive angiopathy 3. Small blood vessel disease 4. Inflammatory diseases of the blood vessels 5. Infectious diseases of the blood vessels 6. Sneddon syndrome 7. Amyloid angiopathies 8. CADASIL 9. CARASIL (Maeda syndrome) 10. Other diseases of the blood vessels •Hereditary endotheliopathy with retinopathy, nephropathy and stroke (HERNS) •Cerebroretinal vasculopathy (CRV) •Hereditary vascular retinopathy (HVR) (linked to 3p21.1-p21.3) •Hereditary infantile hemiparesia with arteriolar retinopathy and leukoencefalopathy (HIHRATL) (not linked to 3p21) •Fibromuscular dysplasia •Moya-moya disease: • sporadic (90%) • familial (linked to 3p24.2-p26, 6, 17) 11. Cerebrovascular aneurisms 11.Vascular malformations 12. Neoplastic diseases: intravascular lymphoma

Atherosclerosis

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a. Atherosclerotic aorta with multiple plaques and adherent thrombi; b. Occlusion of the middle cerebral artery; c. Acute infarction of the ipsilateral cerebral hemisphere affecting deep (basal ganglia) and superficial (white and cerebral cortex) territories; note the enlarged volume of the necrotic hemisphere displacing the corpus callosum and the contralateral hemisphere

Atherosclerosis and small blood vessel disease

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a-c: Different aspects of atherosclerotic lesions including lipid deposition, fibrosis and thickening of the blood vessel wall, and reduction of the lumen. Hematoxilin and eosin (a and b) and silver (c) stained sections

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d-f: Different aspects of small blood vessel disease including thickening and hyalinosis of the arterioles and marked reduction of the intraluminal space. Hematoxilin and eosin (d, f) and trichromic (c) stained sections

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a

Bacterial endocarditis with verrucose septic thrombi at the surface of the valvula (a); multiple hemorrhagic lesions resulting from septic embolism in the frontal lobes

Endocarditis bacteriana

Septic emblism and infarction (arrows)

Inflammatory diseases of the blood vessels Primary cranial and/or cerebral inflammations Takayasu’s arteritis giant cell or temporal arteritis primary angiitis of the central nervous system Kawasaki disease Manifestations of systemic diseases: • systemic lupus erythematosus • polyarteritis nodosa • Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis • Wegener’s granulomatosis • Churg–Strauss syndrome • Sjögren’s syndrome • Behçet’s syndrome • rheumatoid arthritis

Infectious diseases of the blood vessels Bacterial • spirochetal (e.g. lues, borreliosis) • purulent (e.g. streptococcus) • granulomatous (tuberculosis) Viral (e.g. herpes zoster, Epstein–Barr virus) Other microbial (fungal, protozoal, mycoplasmal, rickettsial)

Giant cell arteritis: temporal arteritis Severe focal lesions with altered elastic mebranes, thickening of the intima and middle layers (a) and presence of giant multinuclear cells (b, arrow). Elastin stain

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Cerebellar (a) and lower brain stem (b) infarction (asterisk) associated with involvement of the vertebral arteries by giant cell arteritis (c, arrows)

Primary angiitis of the central nervous system

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Multiple small infarcts (a, arrows) produced by occlusion of arteries (asterisk) with infiltration of lymphocytes, monocytes and multinucleated cells (arrows) in the vessel wall (b)

Rheumatoid arthritis

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Cerebral infarction (a and b) associated with lymphocytic vasculitis and blood vessel occlusion (c-e) in a patient with rheumatoid arthritis

Vasculitis of the carotid artery secondary to bacterial meningitis

Occlusion of the middle cerebral artery (a) producing a massive cerebral infarction of the ipsilateral hemisphere (b) resulting from a septic vasculitis (c) and thrombosis (asterisk) in the context of pneumococcal purulent meningitis

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Tuberculous meningitis, vasculitis and cerebral infarction of the territory of the middle cerebral artery

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Cerebral infarction of the territory of the middle cerebral artery (a) resulting from vasculitis of the middle cerebral artery (b) in the context of tuberculous meningitis

Vasculitis and septic necrosis by Aspergillus

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Cerebral necrosis in the left frontal lobe (a) resulting from embolic occlusion, vasculitis and septic necrosis (b) produced by Aspergillus. Fungi are observed in the lumen, within the blood vessel wall and in the cerebral parenchyma (c). Hematoxylin and eosin (b) and methenamine silver (c) stains

Amyloid angiopathies A. Sporadic forms A1. Alzheimer disease A2. Sporadic amyloid angiopathy B. Familial forms B1. Familial Alzheimer disease Mutations in APP (codons 692–694), PS1, PS2 APP A692G (Flemish mutation), APP E693K (Italian mutation), APP E693G (Arthic mutation), APP D694N (Iowa mutation), KM670/671NL (Swedish mutation) Mutations after codon 200 in PS1 gene, particularly severe B2. Hereditary cerebral hemorrhage with amyloidosis Dutch type. Mutations in codon E693Q in APP B3. Hereditary cerebral hemorrhage with amyloidosis Iceland type. Mutation A68T in the cystatin gene (chromosome 20) B4.Familial amyloidosis Finnish type. Mutations G654A or G654T in the gelsolin gene (chromosome 9) resulting in the deposition of fragments 173–243 and 173–225 of mutated gelsolin B5. Familial British dementia. Mutation of the stop codon 267 (T→A) in the BRI gene (chromosome 13) resulting in the formation of a peptide of 34 amino acids (ABri)

B6. Familial Danish dementia. Duplication of nucleotides between codons 265 and 266 in the BRI gene chromosome 13) resulting in the formation of a peptide of 4 kD (ADan) B7. Familial amyloid polyneuropathy/meningo-vascular amyloidosis. Mutations in the transthyretin gene (chromosome 18); D18G and V30G variants have meningeal and cerebral amyloid deposition B8. Hereditary prion disease with amyloid angiopathy

Amyloid angiopathy

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Cerebral hemorrhage (a) due to sporadic β-amyloid angiopathy (b-e). β-amyloid deposition is found in the wall of the meningeal and cerebral blood vessels (b-e), and in subpial deposits (b). b-e: β-amyloid immunohistochemistry

Amyloid angiopathy

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Degeneration of the cerebral white matter and brain atrophy (a-c) associated with severe cerebral βamyloid angiopathy. d-g: β-amyloid immunohistochemistry

CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

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a: Klüver-Barrera staining showing demyelination of the cerebral white matter. b and c: granular material deposition in the blood vessels of the white matter (arrowheads). d: dense osmiophilic deposits (arrows) in the blood vessels of the skin

CARASIL: Cerebral leukoencephalopathy

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autosomal

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recessive

arteriopathy

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subcortical

infarcts

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Severe atrophy of the white matter with enlargement of the lateral ventricles (a), demyelination as revealed with myelin basic protein immunohistochemistry (b), and thickening of the blood vessel walls without abnormal granular deposition or amyloid deposits (c).

Saccular (berry) aneurisms

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Rupture of a partially thrombosed saccular aneurism of the anterior cerebral artery (arrow)

TL

Saccular aneurism of the anterior cerebral artery (arrow) visualized after dissection of the anterior part of the temporal lobe (TL)

Aneurism of the basilar artery

Rupture (arrows) of a large partly thrombosed aneurysm of the basilar artery

Arteriovenous malformations

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a. Arteriovenous malformation affecting the cerebellum, pons and meninges (arrows); b. arteriovenous malformation involvng the cerebellar vermis (arrow); c. these lesions are composed of veins, arterialized veins, arteries and reduced or absent capillary networks; d. Arteriovenous malformation at the surface of the cerebral hemisphere

Cavernous angioma

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Cavernous angioma in the temporal lobe (a, b) is composed of densely packed thin-walled blood vessels in a fibrous tissue often with siderophages (cc) Cavernous angioma in the spinal cord (d)

Capillary telangiectasia

Capillary telangiectases are composed of aggregations of capillaries with intervening cerebral parenchyma

Intravascular lymphoma

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Intravascular lymphoma (either B or T) is often manifested by multiple cerebral infarcts of small size (a, arrows) and by the occupation of the cerebral blood vessel lumen by neoplastic cells of lymphocytic lineage (b)

Focal brain ischemia

Acute infarct of the territory of the anterior cerebral artery (arrows)

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a and b: Chronic infarcts of the territories of the anterior cerebral artery showing cystic necrosis (arrows) and enlargement of the ipsilateral ventricle (asterisks)

Acute infarct of the territory of the right middle cerebral artery

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a. Acute infarct of the deep territory of the middle cerebral artery affecting the caudate, internal capsule and putamen (arrows) and the territory of the insula (arrow); b. Hemispheric section stained with Klüver-Barrera showing damage of the grey and white matter. ON: optic nerve

Hemorrhagic infarct of the territory of the middle cerebral artery showing enlargement and displacement beyond the midline (vertical line) of the necrotic hemisphere

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a and b: Chronic infarct of the territoriy of the middle cerebral artery showing cystic necrosis, hemicerebral atrophy, and enlargement of the ipsilateral ventricle. b is the hemispheric section stained for myelin

Acute hemorrhagic infarct of the territory of the posterior cerebral artery affecting the inner posterior part of the temporal lobe, including hippocampus, and the primary and associative visual cortices (arrows)

Bilateral infarct of the territory of the posterior cerebral artery affecting the inner posterior part of the temporal lobe, including hippocampus, and the medial nuclei of the thalamus (arrows)

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Chronic infarct of the territoriy of the middle cerebral artery showing cystic necrosis, hemicerebral atrophy and enlargement of the ipsilateral ventricle, and atrophy of the ipsilateral cerebral peduncle, corticopontine and corticospinal tracts (arrows). CC: corpus callosum, IC: internal capsule, CP: cerebral peduncle, PT: pyramidal tract

* a. Acute infarct of territory of the postero-inferior cerebellar artery (PICA, asterisk); b. Acute infarct of the pons (arrows); c. Acute infarct of the cerebellar hemisphere (arrows)

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Acute infarct of the posterior lateral region of the medulla oblongata (arrow); Klüver-Barrera staining. The infarct manifested clinically with Wallenberg syndrome

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a and b. Acute infarct of the territory of short branches of the basilar artery showing necrosis of the pons (asterisk) and axonal swellings (arrows)

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Several examples of lacunar infarcts (arrows) in hemispheric white matter and basal ganglia. CC: corpus callosum, CA: caudate, IC: internal capsule, PUT: putamen, THAL: thalamus

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Pre-lacuna (a, arrow) and lacunar infarct (b, arrow) in the centrum semiovale. Klüver-Barrera staining

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a. Status cribosus (short arrows); b. Lacuna (asterisk); c Perivascular dilatation (arrow)

Binswanger disease

Demyelination of the centrum semi-ovale sparing the short cortico-cortical U fibers, the corpus callosum and the internal capsule (A-C) accompanied by small blood vessel disease and status cribosus in the striatum (D) in a patient with severe chronic arterial hypertension

Subdural hematoma

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Severe ipsilateral cerebral atrophy secondary to a large subacute subdural hematoma in the developing brain

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Adult subdural hematoma (a) resulting in atrophy of the ipsilateral cerebral hemisphere (arrow in b)

Subarachnoid hemorrhage

Lateral view of another subarachnoid hemorrhage involving the surface of the frontal and temporal lobes

Basal view of the brain with extensive subarachnoid hemorrhage and edema

Parenchymal brain hemorrhage

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a and b. Acute cerebral hemorrhages open to the ventricles (asterisks) and producing severe mass effect with displacement of the affected hemisphere beyond the midline (vertical line), herniation of the inner region of the temporal lobe (arrow in b). c. reabsortion of a chronic hematoma (arrow)

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Cerebral hemorrhage open in the ventricle (asterisk) producing a marked mass effect with displacement of the midline (vertical line) and herniation of the inner region of the temporal lobe and midbrain (thick arrow) causing, in turn, occlusion of the ipsilateral posterior cerebral artery and hemorrhagic infarct of its territory (thin arrow)

Hemorrhage in the IV ventricle and brain stem

Hemorrhage affecting the interhemispheric region and hemorrhagic infarct of the distal parieto-occipital convexity. Thrombosis of the superior sagittal sinus was considered causative of the bilteral hemorrhage and hemorrhagic infarct in this case