K Harkness

Ischaemic atheromatous stroke

Cardioembolic, especially secondary to Atrial Fibrillation (AF)

Haemorrhagic, secondary to high blood pressure, abnormal vessels, warfarin

Blocked artery -ischaemic stroke Leak from blood vessel-bleed

Blocked vein-back pressure and swelling, can lead to ischaemia (venous infarct) +_ bleeding

Blood clotting normally occurs when there is damage to a blood vessel. Platelets immediately begin to adhere to the cut edges of the vessel and release chemicals to attract even more platelets. A platelet plug is formed, and the external bleeding stops.

Next, small molecules, called clotting factors, cause strands of blood-borne materials, called fibrin, to stick together and seal the inside of the wound. Eventually, the cut blood vessel heals and the blood clot dissolves after a few days.

Virchows Triad Influences likelihood of thrombosis

Bleeding disorders (von Willebrand disease, hemophilia, hereditary platelet disorders, DIC, ITP, TTP, HUS, and others)

Thrombotic disorders (factor V Leiden, ATIII deficiency, protein C and S deficiencies, antiphospholipid antibody syndrome, and others)

Bleeding Platelet disorders Too few Dysfunctional Too much breakdown Von willebrands Clotting factor

cascade-poor production , congenital low levels Haemophilia,lack of cofactor/Vitamin K

Thrombosis/arterial Too many platelets Hereditary or

acquired ADAMTS13 deficiency

Thrombosis/venous Lack of clotting

cascade inhibitors, Protein C and S deficiency

Internal blockage-local thrombosis or embolus from elsewhere/ clot/infection/foreign body

External compression

Split in blood vessel wall

Inflammation of vessel wall

Arterial

Inflammatory Infective Genetic Toxic Cardiac-non AF Degenerative Traumatic Post radiation

Venous

Infective Inflammatory Haematological

Vasculitides are characterized by inflammation and necrosis of the blood vessel wall.

Large vessels including the aorta are affected in giant-cell arteritis,. An acute phase response is induced by pro-inflammatory cytokines, mainly interleukins (IL) 1, 6 and tumor necrosis factor (TNF) alpha. These are produced by activated macrophages in the vessel wall.

headache, possibly with jaw claudication, visual symptoms, such as diplopia, amaurosis fugax, with blindness as a dreaded complication, or rarely stroke

Diagnosis raised ESR, temporal artery biopsy

Takayasu’s arteritis

The second variant of giant cell arteritis (GCA) affects people younger than 50 years. Granulomatous panarteritis of the aorta and its major branches resulting in localized stenoses, vascular occlusion and aneurysm formation

Temporal arteritis with intense

inflammatory infiltrate within the arterial

wall causing intimal thickening with

nearly complete occlusion of the arterial lumen (hematoxylin and eosin, × 90) Genetic predisposition has been reported with an association to the human leukocyte antigen (HLA)-DRB1 molecule. The target antigen of the CD4+ T cell

immune response in GCA is probably located in the internal elastic layer of the vessel wall which explains that arteries of the anterior intracerebral circulation are infrequently affected because these lack an internal elastic layer .

The primary angiitis of the central nervous system (PACNS) is a rare disorder affecting both medium- and small-sized vessels. Major symptoms of cerebral vasculitis are stroke, headache and encephalopathy.

a combination of high dose steroids and pulsed cyclophosphamide (CYC) is given for induction treatment of CNS vasculitis.

Treatment resistant consider anti- CD20 antibody rituximab.

Methotrexate, azathioprine and mycophenolate mofetil are recommended as alternatives to CYC once remission is achieved.

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Damaged inflamed blood vessels lead to local thrombosis and ischaemia but can also become leaky and cause bleeding.

In cerebral vasculitis, both ischemic and hemorrhagic lesions of different ages

Carotid artery dissection begins as a tear in one of the carotid arteries of the neck, which allows blood under arterial pressure to enter the wall of the artery and split its layers. The result is either an intramural hematoma or an aneurysmal dilatation, either of which can be a source of microemboli, with the latter also causing a mass effect on surrounding structures.

Carotid artery dissection occurs most frequently in the fifth decade of life and accounts for a much larger percentage of strokes in young patients.

It can occur intracranially or extracranially, with the latter being more frequent. Internal carotid artery dissection can be caused by major or minor trauma, or it can be spontaneous, in which case, genetic, familial, or heritable disorders are likely etiologies.

HIV

Vasculitis

VZV

Vasculopathy

Altered Lipid Status

APL Antibodies

Syphilis

Symptoms may include headache, focal neurological symptoms or seizures.

Can see venous infarction and haemorrhage on CT scan. CT venogram investigation of choice

85% of patients with CVT have identifiable risk factors

Thrombophilia, tendency to develop blood clots due to abnormalities of control of coagulation cascade eg Factor V leiden deficiency, Protein C or protein S deficiency,

Chronic inflammatory conditions, eg inflammatory bowel disease, lupus, Behcets

Pregnancy and puerperium

Blood disorders with hyperviscosity, polycythemia, essential thrombocythaemia

Infections of ENT areas eg mastoiditis, sinusitis

Direct injury to the venous sinuses (bull horn)

Antiphospholipid Antibody syndrome, automiimune hypercaogulable state, antibodies against cell membrane phospholipid

Promotes venous and arterial thrombosis

Treatment is with anticoagulants, heparin and warfrain.

Thrombotic angiopathy in kidney in APL syndrome

The exact mechanism of cocaine related stroke remains unclear

Vasospasm-possible via endothelin-1

Cerebral Vasculitis

Hypertensive surges, altered cerebral autoregulation

Cocaine is a potent vasoconstrictor due to its sympathomimetic action, preventing the reuptake of noradrenaline,serotonin and dopamine at pre-synaptic nerve terminals.

However, it also has direct effects on calcium channels,promoting intracellular calcium release from the sarcoplasmic reticulum

Deposition of Abeta amyloid in leptomeningeal and cerebral vessel walls

Reason for excess amyloid depostion unclear. Possible excess production or reduced clearance proposed mechanisms.

Amyloid usually cleared by endocytosis by astrocytes and microglia. Enzymatically degraded by neprilysin and then cleared along perivascular spaces

Vessels are friable and bleed, microbleeds or lobar haemorrhage

CROMIS Trial looking at association of APOE4 status, microbleeds and ICH

Premature large vessel arteriopathy of terminal carotids and vessels of circle of willis

More common in Asian populations

Ischaemia

Seizures

Haemorrhage

The term moyamoya (Japanese for "puff of smoke") refers to the appearance on angiography of abnormal vascular collateral networks that develop adjacent to the stenotic vessels.

Mitochondrial disease MELAS, MERRF

Homocysteinuria Cystathionine beta

synthetase deficiency, autosomal recessive inherited disorder of methionine metabolism.

Patients tall and thin, some learning problems, seizures, young onset vascular disease.

Treat with folic acid and low methionine diet

Metabolic strokelike episodes may be nonvascular and due to transient oxidative phosphorylation (OXPHOS) dysfunction within the brain parenchyma.

A mitochondrial angiopathy of small vessel is responsible for contrast enhancement of affected regions and mitochondrial abnormalities of endothelial cells and smooth muscle cells of blood vessels. The multisystem dysfunction in patients with MELAS syndrome may be due to both parenchymal and vascular OXPHOS defects. Increased production of free radicals in association with an OXPHOS defect leading to vasoconstriction may offset the effect of potent vasodilators (eg, nitric oxide).

The unusual strokelike episodes and higher morbidity observed in MELAS syndrome may be secondary to alterations in nitric oxide homeostasis that cause microvascular damage.

MELAS syndrome has been associated with at least 6 different point mutations, 4 of which are located in the same gene, the tRNALeu (UUR)gene. The most common mutation, found in 80% of individuals with MELAS syndrome, is an A → G transition at nucleotide (nt) 3243 in the tRNALeu (UUR)gene. Abnormal calcium homeostasis resulting in neuronal injury has been suggested as another mechanism contributing to the CNS involvement observed in MELAS syndrome.

Patients with MELAS syndrome have been found to have a marked decrease in the activity of complex I. leading to respiratory chain defects.

Fabry disease results from abnormal deposits of a particular fatty substance (called globotriaosylcera-mide) in blood vessel walls throughout the body. Xlinked recessive Inherited deficiency of the enzyme, alpha galactosidase A, which is normally responsible for the breakdown of globotriaosylceramide. Metabolic Defect This fatty compound (lipid) begins to accumulate. Thus, Fabry disease is often referred to as a "storage disorder" due to this abnormal accumulation

This accumulation occurs in the blood and in the walls of blood vessels. The channels of these vessels become narrowed, leading to decreased blood flow and decreased nourishment of the tissues normally supplied by these vessels.

Particularly affecting vessels in the skin, kidneys, heart, brain and nervous system.

Angiokeratoma seen

Begins in childhood with episodes of pain and burning sensations in the hands and feet.

The disease is slowly progressive and symptoms of kidney, heart and/or neurologic involvement usually occur between the ages of 30 to 45. Many patients are first diagnosed when the accumulated storage material begins to affect kidney or heart function.

A common heart symptom in Fabry patients is mitral valve prolapse, which is a benign condition that is present in approximately 10% of the normal population. More serious, but rarer, complications of Fabry disease include heart disease and strokes.

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy) is an inherited form of cerebrovascular disease that occurs when the thickening of blood vessel walls blocks the flow of blood to the brain. The disease primarily affects small blood vessels in the white matter of the brain. A mutation in the Notch3 gene alters the muscular walls in these small arteries. CADASIL is characterized by migraine headaches and multiple strokes progressing to dementia.

Myxomas are the most common type of primary heart tumor.

The tumor is derived from multipotential mesenchymal cells

General features include dyspnoea, syncope or a mild fever, and weight loss. Auscultation may reveal a mid-diastolic murmur produced by the tumour mass obstructing the valve orifice during ventricular filling.

Investigations show a raised ESR and characteristic echocardiography.

Untreated, the myxoma may result in thrombus formation and subsequent embolism, and permanent mitral valve obstruction.

Surgical removal is completely curative.

Most cases are caused by infection with bacteria. A small number of cases are caused by infection with fungi. To develop this infection, you need to have some bacteria or fungi in the bloodstream. The blood usually does not contain any bacteria or fungi. However, some may get into the blood if you have an infection or wound in another part of the body. In particular, dental and mouth infections are situations where bacteria can quite easily get into the bloodstream. People who inject street drugs may also inject bacteria or fungi into their bloodstream if they use dirty or contaminated needles.

PFO and Atrial septal aneurysm-anticoagulate

PFO and recurrent episodes?? Closure device

Arterial

Inflammatory Infective Genetic Toxic Cardiac-non AF Degenerative Traumatic Post radiation

Venous

Infective Inflammatory Haematological

Thrombosis Bleeding