Stroke Flashcards
what is neurodegeneration?
Progressive damage or death of neurons leading to a gradual deterioration of the bodily functions controlled by the affected part of the nervous system.
what are some causes of brain damage?
- genetics
- trauma
- tumour
- alterations in blood flow
what is a cerebral stroke?
- Blockage/interruption of cerebral artery
- Death of cells
- symptoms: depend on location
what is the prevalence of stroke?
in the Uk
- 250-400 strokes per 100 000 people
- 3rd cause of death
- 1st cause of disability (in adults)
what are Ischemic stroke?
80% of strokes
- brain deprived of blood
- due to blood clots (thrombus) blocks flow of blood in brain or fatty plaque or blood clot (embolism) breaks away and flows to brain where it blocks the artery
what is haemorrhagic stroke?
- 20 % of strokes
- bleeding in brain
- breaks blood vessel (aneurysm) in brain
what are the risk factors of a stroke?
- all stages of life (over 400 childhood strokes per year in UK, 1 in 4 strokes in working adult age)
Medical conditions - High blood pressure, diabetes, atrial fibrillation, high cholesterol
Lifestyle - Smoking, drinking, diet, exercise
Family history and ethnicity - Likely related to incidence of other risk factors e.g. high cholesterol, diabetes
Specific for women - Pregnancy, contraceptive pill
clinical symptoms of a stroke
- Sudden or gradual onset
- One-sided limb weakness/paralysis
- Confusion, loss of speech/vision
- Headache
- Loss of consciousness
results in dysfunctional cognitive and
motor behaviour
… determined by size and location of cell loss
cognitive impairments from a stroke
- Amnesia
- Inattention
- Confusion
- Depression
- Mood and behaviour changes
depression after a stroke
- Common after stroke
- Not simply a consequence of physical effects
- Patients with post-stroke depression (PSD) often differ from those with primary depression in that they have more cognitive impairment (memory and concentration problems), irritability, more psychomotor slowing, and more mood liability.
Transient Ischemic Attack (TIA)
- Transient episode of neurological dysfunction without acute tissue death
- Disruption of CBF
- Mini-strokes
Risk factor for subsequent stroke - 10% strokes within 90 days of TIA
Silent strokes - No visible symptoms
Ischemic stroke – core and penumbra
- The core area is where blood flow is below critical, leading to cell death
- Penumbra is the reversibly injured brain tissue around the ischemic core
- over time after a stroke has occurred then the area of irreversibility injured brain tissue increases
what is cerebral stoke - patholgy
massive cell death
- primary cause of cell death is excessive amounts of glutamate
ischemic lesion = excitotoxic lesion
- causes a cascade of further complex events
- inflammation, cell death, reperfusion
inflamation
- Sodium ions – water, swell, inflammation
- Microglia – become phagocytic
- Phagocytosis = ‘cell-eating’
- Blood-brain barrier breakdown – influx of blood-borne immune cells (neutrophils, macrophages)
- Oedema formation, adhesion molecules, cytokines
cell death in a cerebral stoke
neurocrosis → low oxygen → depleted ATP → cellular swelling and membrane break down
apoptosis → triggers programme death → intraceelular signalling (capases) → cells fragment into vesicles → phagocytosis by neighbouring cells
Cerebral stroke – reperfusion injury
Hyperfusion
- a major increase in cerebralblood flow (CBF), well above metabolic demands of CNS tissue
Intracranial haemorrhage/edema
- Mortality 36-63%
80% patients significant morbidity
How does Excitotoxicity lead to cell death?
- decrease in blood flow → mitochondria mysfunction → disruption of Ion homeostatis → NMDAR → cell death
OR
decrease in blood flow → mitochondria mysfunction → less ATP → cell death
what happens in the core and Penumbra during a cerebral stroke?
Core
- Rapid necrotic cell death
- Mainly due to excessive NMDA receptor stimulation
- further glutamate release
Penumbra
- Slower (days) apoptotic cell death
- More moderate NMDA receptor hyperactivity
Amino acid neurotransmitters
- Excitatory = glutamate and aspartate
- Inhibitory = GABA and glycine
- Glutamate and GABA – closely related
glutamate receptors
Iontropic
- NMDA
- AMPA
- Kainate
Metbotropic
- Many subtypes
what do excess amino acids do?
Excess amino acids results in prolonged depolarization of receptive neurones which leads to their eventual damage or death
what are some cerebral stroke treatments?
- Pharmacological
- Thrombolysis
- Aspirin
- Modifiable risk factors
- Physiotherapy
How do drugs treat strokes?
they alter synaptic function by increasing/decreasing neurotransmitters
drugs and receptors
Drugs affect neurotransmitter functioning
- Agonist = increases NT function
- Antagonist = decreases NT function
Sites of actions of drugs
- Direct = attaches to NT binding site (post-synaptic)
- Indirect = drug binds to alternative binding site (pre-synaptic)
- Non-competitive binding = does not compete with NT
Drugs
- Direct agonist/antagonist
- Indirect agonist/antagonist
what is Neuroprotection?
- Aims to protect neurones from injury
- Limited by: Therapeutic time window, Effectiveness/outcome
what has it been proven to be the best pharmacological method to treat a stroke, but failing clinical trials?
- NMDA receptor antagonists
- Proved to be the most successful compounds ever generated to protect against cell death in vitro and in vivo (models)
- Various compounds developed
- BUT is failing clinical trials due to: Lack of efficacy, Toxic side effects
what is Thrombolysis?
trying to break down the blood clot
drug treatment for thrombolysis
Tissue Plasminogen Activator (t-PA)
- Thrombolytic
- only drug licensed in US for stroke
- most affective if administed within 3 hours
- CT scan used to determine which type as doesn’t work on haemorrhagic stroke
surgical treatment for Thrombolysis
Carotid endarterectomy
- To remove build-up of fatty deposits within arteries
- Intra-arterial thrombolysis
how can asprin be used in strokes?
- Antiplatelet agents (and anticoagulant)
- Prevention of recurring strokes
- Reduction of severity of stroke
- Inhibit production of thromboxane
- makes platelets less sticky
what are cerebral stroke risk factors?
- High blood pressure*
- Smoking
- Physical inactivity
- Obesity
How can physiotherapy be used to help stroke symptoms?
- Weakness/paralysis
- Improve motility/avoid injury
- Everyday activities
- Independent living
- Exercise, manipulation, massage, skills training, electrical treatment
