STROKE

Stroke is an abrupt-onset focal neurologic deficit that occurs as a result of interruption of

cerebral blood supply lasting at least 24hrs and is of presumed vascular origin.
There are two major types:
Hemorrhagic stroke and ischemic stroke

Ischaemic stroke
-Thrombotic. Thrombotic occurs when a thrombus, or blood clot, develops in a blood vessel in
the brain and reduces the flow of blood to the brain
-Embolic( cardio or non cardioembolic origin) stroke. Embolic stroke is caused when a clot
travels from elsewhere to block a vessel in the brain

We can also classify stroke based on the type of artery affected, i.e. large or small artery
The cerebral hemispheres are supplied by 3 major arteries:
Anterior cerebral artery(ACA)
Middle cerebral artery(MCA)
Posterior cerebral artery (PCA)

Anterior and middle cerebral artery arise from the internal carotid artery and these vessels help
with anterior circulation. Any infarction in them causes anterior circulation stroke

The posterior cerebral artery arises from the basilar artery. Any infarction in them causes
posterior circulation stroke

NB: Cryptogenic stroke is ischaemic or hemorrhagic stroke of unknown origin

A condition which has symptoms that are stroke like but not of vascular origin is a stroke mimic
(stroke mimic is mostly due to epilepsy, neuropathy and hypoglycaemia. SBP<-140, history of
DM, no history of arrhythmia. tPA worsens a mimic)

Hemorrhagic stroke
-Subarachnoid hemorrhage: bleeding into the fluid filled subarachnoid space between the brain
and skull due to rupture of intracranial aneurysm, arteriovenous malformation(AVM) or trauma.
Vasospasms can occur 5 to 10 days post SAH due to products of the spilled blood irritating the
vessels causing contraction and spasms, hence reducing the lumen and causing a secondary
stroke
-Intracerebral hemorrhage: bleeding into the brain parenchyma itself
-Subdural hematoma: bleeding under the dura

Aetiology
Sub arachnoid is caused mostly by rupture of an aneurysm(usually berry aneurysm) or
arteriovenous malformations and sometimes trauma
Subdural hematoma- trauma
Intracranial hemorrhage- uncontrolled chronic hypertension
Ishemic: embolism, thrombus, small vessel occlusion, systemic hypoperfusion, atherosclerosis,
increased ICP - may cause tamponade, spasms
NB: An aneurysm secondary to an infection is a mycotic aneurysm or infected aneurysm, caused
by fungi or other microbes

Risk factors
-Modifiable:
Uncontrolled hypertension
Smoking
Dyslipidemia
Diabetes
Cardiac disease
A fib
Obesity
Sedentary lifestyle
Congestive heart failure etc

-Non modifiable
Age
Sex
Race
Low birth weight: LBW is associated with structural and functional changes in the vascular tree,
which have implications for cardiovascular health in adult life.
Genetics

Signs and symptoms of stroke

More often than not the presenting symptoms are determined by the parts of the brain affected
Anterior circulation stroke : Aphasia
Posterior circulatory stroke: Vertigo, Diplopia(double vision)
General signs and symptoms
Double vision, headache, inability to speak, vertigo, slurred speech, face drop, pareisis, plagia
(hemi& quadri) sudden weakness
NB: For hemorrhagic stroke,symptoms occur rapidly due to increased ICP and may include
headache, nuchal rigidity(stiff neck), pain, vomiting and then a coma
Paresis- weakness
Plegia - paralysis
Weakness of one half of the body- hemiparesis
Weakness of all 4 limbs- tetraparesis or quadriparesis
Weakness of the lower part of the body. From waist downwards- paraparesis
Same applies for plegia
Dysarthia is weakness in the muscle for speech production resulting in slurred speech
Aphasia: A language disorder that affects a person's ability to communicate
Types
-Receptive: patient can speak although usually non-coherent or disoriented, but cannot
understand. Also called non fluent aphasia or Wernicke's aphasia
-Expressive: the person understands what you're saying but can't communicate back. Also
known as fluent aphasia or Broca's aphasia

Diagnosis
History: to distinguish between stroke and TIA
CT/MRI
FBC, ESR(inflammatory marker for carotid atherosclerosis)
Blood glucose, blood urea, electrolytes
ECG(To rule out cardiac etiology)
Cerebral angiography
For Ischaemic, hypodense(dark patches)
Hemorrhagic, hyperdense(white patches)

NB: History alone wouldn't be enough so we dont wait. Within 45mins of presentation to the
hospital, a diagnosis should have been made to know if the patient is a candidate for r-TPA since
the door to needle time is 60mins, though the symptoms could help point to a particular type of
stroke but none of the symptoms are pathognomomic for stroke hence imaging with the CT or
MRI is the gold standard for diagnosis. Clinically, along with the normal definition of stroke, the
BP may be unresponsive to antihypertensives, sudden onset of severe headache(the patient's
worst ever headache), stiff neck, photophobia, blurred vision, etc.

Management
In the acute setting onset of ischemic stroke
-Fibrinolytics: Alteplase is the only tissue plasminogen activator approved for ischemic stroke. It
should be given within 4.5hours of onset of stroke.
Dose: 0.9mg/kg up to a max of 90mg, of which 10% of the total dose us given by initial IV bolus
over 1minute and then the rest is infused over 60mins
Some amount of gentamicin can be found in atleplase because gentamicin is employed in its
production hence alteplase should not be administered to a patient hypersensitive to gentamicin
Thrombolytics are not to be administered when BP is uncontrolled, there is increased risk
of hemorrhage if you use it while the BP is >185/ 110mmHg. The BP target in Stroke is
<185/110mmHg, so the BP has to be reduced before alteplase is used in such instances. It's not
an absolute exclusion criteria

Generally, BP should not be reduced in the acute setting.You only reduce the BP if its above
185/110mmHg and the patient is a candidate for reperfusion therapy with alteplase.

The elevated BP is a compensatory mechanism to maintain normal blood flow to organs. In

effect lowering the BP can worsen the ischaemia by causing hypoperfusion

NB: In patients with BP ≥220/120mmHg who did not receive IV alteplase or EVT and have no
comorbid conditions requiring acute antihypertensive treatment, the benefit of initiating or
reinitiating treatment of hypertension within the first 48 to 72 hours is uncertain. It might be
reasonable to lower BP by 15% during the first 24hours after onset of stroke.

According to the STG, the threshold for BP management is 180/110 mmHg and BP should not
be reduced by more than 20% over 24hours since rapid reduction of BP in acute stroke could
cause hypoperfusion to certain parts of the brain
This differs from the AHA/ASA. According to the American guidelines too, the threshold for BP
reduction is 220/120mmHg and it should not be reduced by more than 15% in the first 24hours.

This is managed as a case of hypertensive emergency hence either labetalol or hydralazine can
be used but most clinicians prefer labetalol to hydralazine because of reduced risk of sudden
drop in BP compared to hydralazine.

NB: Streptokinase is obtained from Beta-haemolytic streptococcus hence its highly allergenic
compared to other forms of tpa. It should not be repeated after 4 days of therapy since anti
streptococcal antibodies are produced to neutralise its effect. It's rendered ineffective after
4days of continuous use. The antibodies remain in circulation for up to a year hence you can
repeat within 4days but after the 4th day, it cannot be repeated for up to a year.
Streptokinase is not used in stroke due to increased risk of bleeding( non fibrin specific).

In the absence of Alteplase, Aspirin is administered at a dose of 300mg for 2 weeks then 75mg
daily. Therapy is initiated within 48hrs of the stroke(24hrs after alteplase)
According to the CAST and IST trial, aspirin started within 48hours of onset of stroke resulted
in less fatal strokes and fewer deaths. Aspirin is initially given at a higher dose to acetylate all
platelets that are already formed to prevent further clot formation. The life span of platelets is 5
to 7 days. Other references say up to 10days so we will need to clear all the already formed ones
before maintenance therapy is initiated. The maintenance dose is to prevent aggregation of the
new platelets formed
Other antiplatelets used
Clopidogrel 75mg daily: it inhibits the binding of adenosine diphosphate (ADP) to its platelet
P2Y12 receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa
complex, thereby inhibiting platelet aggregation
Aspirin/ extended release dipyridamole 25/200mg twice daily: inhibits phosphodiesterases and
augments prostacyclin related aggregation inhibition. It also inhibits the uptake of adenosine
into platelets.

NB: In emergency situations like STEMI and acute stroke, it's preferable to go in for either
chewable or dispersible aspirin for a rapid onset of action.
If the patient is unconscious, dispersible aspirin via NG tube
-High intensity statins irrespective of lipid profile for the pleitropic effects(Lowers C- reactive
protein levels, improvement of endothelial cell function, increased nitric oxide bioavailability,
antioxidant properties, inhibition of inflammatory responses, anti thrombotic effects and
stabilization of atherosclerotic plaques).
-PPIs to prevent stress induced ulcer
-Turning in bed every 2 hours to prevent bed sores
-Oxygen if the patient is hypoxic, to maintain spo2 at >94%
-Hypoglycemia (3.3 mmol/L ) should be corrected and blood sugar should be maintained
between 7.8-10mmol/L
-Maintain body temperature. Hypothermia is neuroprotective.

Long term management of ischemic stroke

-Hypertension: the ACEIs or ARBs alone or with thiazides are preferred. This is because of 2
major trials. The PROGRESS and LIFE trial that showed other benefits of these medications
aside BP lowering
Perindopril monotherapy or with indapamide - Perindopril pRotection aGainst REcurrent Stroke
Study(PROGRESS)
Losartan - Losartan Intervention For Endpoint reduction in Hypertension study (LIFE). Losartan
was compared to metoprolol. Though both caused a similar reduction in BP but losartan was
found to be superior to metoprolol by causing a 24% reduction in cardiovascular events
Some clinicians don't prefer using methyldopa because of the risk of CNS depression
associated with it. This is likely to impair their objective assessment especially GCS which is
usually used as an examination tool in stroke patients
-Anticoagulants if it’s from a cardioembolic source. Depending on CHADS vascular score,
warfarin or DOACs
-Antiplatelets
-Statins
-Antidepressants, eg. Fluoxetine, sertraline
According to the popular FLAME trial, fluoxetine is used for motor recovery after acute
ischaemic stroke. Patients with ischaemic stroke and moderate to severe motor deficit
benefitted from the early prescription of fluoxetine with physiotherapy and had enhanced motor
recovery after 3 months.
Dose was 20mg daily mane because of the risk of insomnia associated with nightime dosing

FLAME trial recruited only ischemic stroke patients whereas FOCUS trial recruited both ischemic
and hemorrhagic stroke patients

FLAME trial assessed outcomes at 3months therapy but FOCUS trial realised when therapy is
continued up to 6months virtually no significant effects is seen so outcome assessment for
FOCUS trial was at 6months

Sample size for FLAME trial was small with only 118 patients whereas FOCUS trial used about
3127 patients which was relatively larger

New trials are being conducted, AFFINITY and EFFECTS trials

In hemorrhagic stroke, studies suggest that fluoxetine may worsen bleeding since it inhibits
serotonin reuptake which is a component present in platelets necessary for aggregation. This
is really yet to be established clinically but theoretically it could potentially worsen hemorrhagic
stroke
Also SIADH (syndrome of inappropriate antidiuretic hormone secretion) is a common
complication of subarachnoid hemorrhage (SAH) and antidepressants especially SSRIs.
Because of the SIADH syndrome which is a class effect of antidepressants, the chances of
seizures in patients with hyponatremia is increased.
Fluoxetine is avoided in those 24years and below because of suicidal ideations

NB: Since rivaroxaban is metabolized by CYP3A4, the use of antidepressants that are inhibitors

of this isoenzyme, such as fluoxetine, sertraline, paroxetine and fluvoxamine must be avoided

-Neuro protective agents: Citicholine, Piracetam, Neurozan

Citicoline is a precursor which is essential for the synthesis of phosphatidyl choline, one of the
cell components that is degraded in cerebral ischemia to free fatty acids or free radicals. So in
administering Citicoline, it gives a neuroprotective effect and has been shown to be beneficial in
memory, cognition and post stroke effect. It has also been shown to be effective in hemorrhagic
stroke
In the hospital the dose given is 1g daily and could be increased to 1g bd. Common brand the
market is Somazina
Citicoline has anti-oedematous effects
Piracetam is a nootropic. It is derived from GABA and works on AMPA receptors stimulating
them to improve signal transmissions between neurons improving cognition and nerve system
functioning. It has in addition, hemologic effects thereby decreasing blood viscosity and
improving RBC membrane deformability to allow free flow of blood in ischemic areas of the
brain.
It also decreases platelet aggregation which is beneficial in ischemic stroke. It is however
contraindicated in hemorrhagic stroke because of its effect on platelets and blood viscosity
The maximum daily dose is 24g especially in cortical myoclonus but in cognitive disorders like
stroke, 1.2g to 4.8g daily in 2-4 divided doses
So mostly 800mg to 1.6g tds

BP management in acute hemorrhagic stroke

Just like in ischemic stroke, the targets are the same but the only difference is in ischemic
stroke you want to reduce the BP gradually within the first 24hrs by not more than a certain
limit to prevent cerebral hypoperfusion whereas in hemorrhagic stroke(ICH) you want to reduce
the BP aggressively in the first 24hrs if the SBP >220mmHg since aggressive BP reduction in
hemorrhagic stroke has been shown to reduce hematoma expansion which is very vital in terms
of neurologic deficits. The larger the hematoma formation the higher the neurologic deficits
If the SBP is between 150-220mmHg, reduction to 140 is safe

-Nimodipine is given in SAH due to delayed cerebral ischaemia from vasopasms. You could have
ischaemia occurring in hemorrhagic stroke from vasopasms
Dose: 60mg PO 4hourly for 21 days on an empty stomach at least 1 hour before or 2 hours after
meals.
Food decreases bioavailability by about 38% and plasma concentration by 68% compared to
fasted state hence an hour before or 2hrs after meals. The instructions with respect to food
applies to capsules and oral solution. The tablets is without regards to food but it has to be

®
consistent.
Nimotop which is a tablet
Nimodipine is the Ca channel blocker with minimal effects on conduction in heart, its primary
effect is in cerebral vessels, it is highly lipophilic, allowing it to cross the blood-brain barrier.
The vasopasms start 4 days or 96hrs after onset of haemorrhagic stroke, peaks from 5th day to
9th day and continues up to 21days.
The nimodipine is administered as a prophylaxis hence it should be started before the 4th day to
serve the prophylactic role. It has a half life of 1-2hrs hence more frequent administration
Give 30mg 2hourly in patients who are at risk of severe hypotension from the 60mg. If the
patient can't swallow, it is administered enterally through NG tube
In liver cirrhosis, 30mg every 4hours with close monitoring of BP and HR. Extensive hepatic
metabolism via Cyp 3A4 and also first pass metabolism hence dose reduction needed
The IV form is for treatment. There is a risk of life threatening hypotension and sudden death
when given via IV
-Mannitol to reduce raised ICP
0.2-2.0g/kg every 6-8hours for 48hours
Give for 15-30 minutes
Mannitol increases cardiac preload and cerebral perfusion pressure, which contributes to a
decrease in intracranial pressure through cerebral vasoreactivity.

NB: Mannitol should be administered within an hour because it could cause rebound increase
in intracranial pressure. When administered over a long period, it creates an osmotic gradient
further drawing more water into the brain

*Signs of raised ICP

Severe headache
Meningism
Nausea and vomiting
Seizures
High blood pressure
Irregular breathing
Bradycardia(Cushing triad)
Blurred vision
Dilated pupils
Decreasing level of consciousness

Mannitol via inhalation in conditions such as cystic fibrosis is contraindicated in asthmatics with
FEV1 less than 30% because of risk of bronchial hyper-responsiveness but when given IV, such
bronchospasm is not really seen hence can be used via IV in asthmatics with caution.

Other agents for raised ICP

-Hypertonic saline, 300ml of 3% over 20mins. It can be given at 1-2ml/kg/hr
-Furosemide but not routinely used
-Dexamethasone could be used but the evidence surrounding it is controversial. The evidence
supports it more when it is used in raised ICP secondary to cerebral neoplasms or tumors.
-Acetazolamide too has been used. Especially preferred for raised ICP in paedics. 250mg t.i.d
for acute hydrocephalus

-Morphine for headache 4mg qid

Use with caution. It can worsen cerebral haemorrhage due to possible constipation, i.e. Valsalva
manoeuvre; straining increases the already raised ICP

-Tranexamic acid can also be used to avoid rebleed, 1g t.i.d for 72 hours

-Air conditioning: Hypothermia has been shown to be neuroprotective. Although studies are still
ongoing, the benefits seem to be encouraging

Agents for pyrexia in stroke patients

-Acetaminophen if the temp is 37.5 and above
Dantrolene is administered when there is neuroleptic malignant hyperthermia
-Metamizole(analgin): 1g tds.
Maximum of 5g for IV and 4g for oral
It's multifactorial but one hypothesis is bleeding causing elevated temperature

One clinical sign used to check for rebleeding in stroke patients is sudden temperature spikes
even though it is not objective since many conditions can cause that.
Fever has been shown to accelerate ischemic neuronal injury hence the neuroprotective effect of
hypothermia.

Complications
Hydrocephalus
Bed sores
Aspiration pneumonia
DVT

Bed sores: the old terms used to be decubitus ulcer and pressure ulcer but the term has been
changed to pressure injury because not all bedsores are ulcerative
4 main stages
Stage 1 - Non blanchable erythema with intact skin
Stage 2 - partial thickness skin loss
Stage 3 - full thickness skin loss
Stage 4 - full thickness skin and tissue loss

Prevention
2 hourly bed turning
Zinc oxide cream has been used as a skin protectant and also astringent. It also prevents
irritation
Sudocreme
Stage 1 and 2 could be managed with medications
Stage 3 and 4 require surgical reconstruction

Infected bedsores
Wound dressing for bedsores infected with Pseudomonas aeurogiosa
-Acetic acid
-Savlon
-Normal saline
-Debridement. Necrotic tissue will promote bacteria growth
Pawpaw leaves- papain
Pineapple - Bromelain

Preparations available
Debridace- urea and papain
Debriz 10 - serratiopeptidase
Chymoral- chymotrypsin-trypsin
Therapeutic maggots, etc.
Q1
A patient who is being managed as a case of stroke was put on IV Analgin 1g tds. After 2 days
of therapy, the urine of the patient was found to have turned red. The resident on duty ordered
for a retic count which was found to be normal
1.What could have accounted for the change in urine colour?
2.Why did the resident order for a retic count to be done
3. If that same patient should develop angina-like symptoms with hypotension and bradycardia
soon after analgin administration. What syndrome would that be?

Answers
1. Metamizole has a harmless metabolite called rubazonic acid which can cause red
discoloration of patient's urine
2. The resident probably suspected hemolysis and in hemolysis retic count would be high as a
compensatory mechanism for loss of RBC
He could also be suspecting metamizole toxicity causing aplastic anemia. In that case, the retic
count will determine exactly what is happening. In haemolysis, retic count would be high and in
aplastic anaemia, retic count will be low
3. Kounis syndrome