Download Objectives 53 - u.arizona.edu

1. Embolic stroke syndrome
- Ischemic stroke can occur when blood clots form at distant sites and travel to the brain carried
by arterial blood flow until they lodge in smaller arteries, blocking blood flow to a section of
the brain which suffers damage due to lack of O2; brain is most vulnerable organ to ischemia
(quick irreversible damage)
- embolic strokes caused by a thrombus that forms at a distant site
Cardioembolic stroke - blood clots form in atrium of heart during atrial fibrillation; can
occur in distribution of any of the major arteries
Arterioembolic stroke – blood clots form in the extracranial carotid arteries due to rupture of
an atheromatous plaque and subsequent thrombus formation; can cause syndromes relating to
the distribution of the middle or anterior cerebral artery
- ensuing stroke syndrome depends on where thrombus ends up
Lacunar stroke syndrome
- strokes caused by an occlusion of an artery directly at the site of the atherosclerotic process
- affects small arteries arising directly from the Circle of Willis; these small arteries are
responsible for providing blood flow to structures at base of brain: basal ganglia, thalamus,
internal capsule, rostral brainstem
- ensuing damage is limited and forms a spherical area with a small radius
- permanent UMN deficit can occur if lacunar stroke interrupts the CST as it passes through
the internal capsule or through the brainstem
2. Penumbra and stroke treatment
Penumbra
- shadow; area of brain tissue surrounding center of stroke
- surrounding brain tissue receives enough collateral blood flow that survival of neurons is
possible
- acute onset of stroke  penumbra cells do not receive enough blood flow/oxygen to
function properly and therefore contribute to the deficit; however, they receive sufficient
blood flow/oxygen to prevent cell death
- survival of penumbral neurons depends on timely treatment
Fates of penumbral neurons:
1. Survival – neurons may be stunned; as they recover to full function, they contribute
to early recovery
2. Apoptosis – programmed cell death; initiated by release of mitochondrial factors
(cytochrome c) and activation of caspases (proteolytic enzymes)  fragmentation of nuclear
DNA; nervous system shaped by sculpting, rather than building-up; apoptosis is critical in
selective survival of neurons with proper connections; during development  retrograde
axonal transport of growth factors (GFs) from target tissue neuron is innervating protects
neuron from apoptosis; neurons not making proper connections are winnowed out; ischemia
(stroke) triggers apoptosis inappropriately
- thus growth factors and anti-apoptotic approaches are being evaluated as
experimental therapies for rescuing penumbral neurons
3. Necrosis – less orderly process  leads to cellular swelling, lysis, and provokes an
inflammatory response  secondary injury; initiated when cells lose ATP production 
ionic gradients break down (failure of Na/K ATPase pump)  depolarization allows high
levels of intracellular Ca2+
- NMDA channel is a major player in allowing Ca2+ entry during prolonged
depolarization; NMDA blockers effective in limiting damage of stroke in animal models, but
not in humans because:
a. window of opportunity is too short to be clinically relevant
b. treatment applied without determining ratio of penumbra to core
c. necessary to block more than one step in the ischemic cascade to realize a
meaningful effect
- factoring in extent of penumbra compared to the ischemic core  help select patients
and uncover an effect obscured by heterogeneity of clinical strokes compared to wellcontrolled uniform lesions produced in experimental stroke models
Thrombolysis
- if stroke diagnosed within 3 hours of onset of symptoms  thrombolytic agents administered
to enhance dissolution of clots and restore profusion of the brain; risk includes hemorrhage
in brain (after 3 hours, risk is to great to administer thrombolytic agents)
- new techniques involve infusing thrombolytic agents at site of clot by catheter
through arterial system; future of anti-necrotic and anti-apoptotic strategies will extend
window of opportunity for thrombolysis
3,4,5 Mechanisms by which recovery from stroke naturally occurs
- recovery depends on the degree of plasticity in the brain; adults continue to learn and this
requires a degree of both structural and functional plasticity; experimental methods include
enhancing the latent capacity of the adult brain to undergo plastic changes
- edema (swelling) of infarction occurs (peak at 4 days after stroke onset) due to inflammatory
response provoked by necrosis and compromise of blood-brain barrier; severe edema can
cause herniation syndromes; patient may improve with resolution of edema
4. Resolution of diaschisis
- stroke can have remote effects on brain function
- small infarct in thalamus  widespread cortical dysfunction (since cortex is dependent on
an excitatory thalamic input for full activation) or aphasia (secondary inactivation of language
cortex)
- resolution of diaschisis contributes to stroke recovery; involves plasticity in recruitment of
alternative excitatory inputs to remote area affected by diaschisis
5. Cortical reorganization
- cortical reorganization occurs following stroke in the primary motor cortex (homunculus
resides here)
- if stroke occurs in hand portion of homunculus, the somatotopic organization changes so that
adjacent areas take over hand function; new connections can also form and new activity can
appear in the supplementary (premotor) cortex suggesting plasticity in function
- minor uncrossed portion of CST may be called into play after stroke; this uncrossed portion
has stronger innervation to proximal and axial muscles; recovery is less for distal musculature
of upper extremity
- one mechanism of recovery can be recruitment of contralateral homologous cortex
- high degree of hemispheric specialization (hemispheric dominance) limits this mechanism
of recovery
- a critical period may exist during which post-stroke cortical reorganization occurs;
rehabilitation techniques should be carried out early to be fully effective
- certain treatment modalities used to enhance this process of plastic cortical reorganization
following stroke including constraint techniques in which patient is forced to use involved
limb (also includes use of drugs that boost NT levels like dopamine and serotonin)
- subthreshold cortical stimulation with electrical current can improve cortical reorganization
in motor strip following stroke in animals
Compensatory strategies
- additional functional recovery obtained as patients being to volitionally employ compensatory
strategies; alternative communication strategies in patients with aphasia and apraxia
- use of strategies requires patient to be aware of deficit