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

b c

a

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

a

d e f

c b

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

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

Atherosclerosis and small blood vessel disease

Endocarditis

bacteriana

a

b

Bacterial endocarditis with verrucose septic thrombi at the surface of the

valvula (a); multiple hemorrhagic lesions resulting from septic embolism in

the frontal lobes

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)

*

*

*

*

a b

a b c

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

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

*

a

b

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

a b

c d e

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

c

a

b

*

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

a b

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

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

a b c

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

a b

d e c

Amyloid angiopathy

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

a

d

c b

f e g

Amyloid angiopathy

Degeneration of the cerebral white matter and brain atrophy (a-c) associated with severe cerebral β-

amyloid angiopathy. d-g: β-amyloid immunohistochemistry

d

c

a

b

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

CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and

leukoencephalopathy

CARASIL: Cerebral autosomal recessive arteriopathy with subcortical infarcts and

leukoencephalopathy

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).

a b c

*

TL

Saccular (berry) aneurisms

Rupture of a partially thrombosed

saccular aneurism of the anterior

cerebral artery (arrow)

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

a

d c

b

Arteriovenous malformations

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

a c

d

b

Cavernous angioma

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

a b

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)

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

Focal brain ischemia

*

* *

AC

a b

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

ON

a b

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

a b

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)

IC

IC

CP

PT

CC

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

b c

a

*

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)

a

b

*

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)

Acute infarct of the posterior lateral

region of the medulla oblongata

(arrow); Klüver-Barrera staining.

The infarct manifested clinically

with Wallenberg syndrome

CC

CC

CC

CC

CC

IC

IC

IC

IC

CA

CA

CA CA

PUT PUT

PUT

PUT

PUT

THAL

THAL

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

Pre-lacuna (a, arrow) and lacunar

infarct (b, arrow) in the centrum semi-

ovale. Klüver-Barrera staining

a

b

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

a c b

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

Severe ipsilateral cerebral atrophy

secondary to a large subacute subdural

hematoma in the developing brain

Adult subdural hematoma (a) resulting in atrophy of the

ipsilateral cerebral hemisphere (arrow in b)

a

b

Subarachnoid hemorrhage

Basal view of the brain with extensive

subarachnoid hemorrhage and edema

Lateral view of another subarachnoid

hemorrhage involving the surface of the frontal

and temporal lobes

* *

a

b

c

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)

Parenchymal brain hemorrhage

*

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