Stroke

Case Vignette

A 68-year-old woman presents with weakness on the right side of the body.

Questions:

• Take a history to unravel the cause.
• What are the important aspects of neurological examination you would be interested in?
• What are your differential diagnoses?

Investigation

• What type of investigation is this?
• What are the abnormalities?
• What is the pathologic diagnosis?
• Suppose she develops progressive depreciation in level of consciousness soon after admission, what are 2 possible causes?

• How will you manage the reduced level of consciousness?

CURRENT CONCEPTS

• Sudden focal or global neurological deficit resulting from spontaneous haemorrhage or infarction of the central nervous system with objective evidence of infarction irrespective of duration of clinical symptoms. Note: CT/MRI provides the objective evidence of stroke diagnosis.

or

An acute episode of focal dysfunction of the brain, retina, or spinal cord lasting longer than 24 hours, or of any duration if imaging (CT or MRI) or autopsy show focal infarction or hemorrhage relevant to the symptoms.

NB: The definition includes subarachnoid hemorrhage.

TIA:

• Transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without evidence of acute infarction.
• No objective evidence of acute infarction in the affected region of brain or retina.
• CITS: Cerebral Infarction with Transient Symptoms
• CIND: Cerebral Infarction No Deficit (Silent stroke)
• Most (90%) TIAs last 10-30 mins.
• Up to 50% develop stroke within 24-48 hrs.
• 10-20% develop stroke within 90 days.

Definition of Stroke

The term "stroke" should be broadly used to include all of the following:

Definition of CNS infarction: CNS infarction is brain, spinal cord, or retinal cell death attributable to ischemia, based on:

1. Pathological, imaging, or other objective evidence of cerebral, spinal cord, or retinal focal ischemic injury in a defined vascular distribution; or
2. Clinical evidence of cerebral, spinal cord, or retinal focal ischemic injury based on symptoms persisting ≥24 hours or until death, and other etiologies excluded. (Note: CNS infarction includes hemorrhagic infarctions, types I and II)

Definition of ischemic stroke: An episode of neurological dysfunction caused by focal cerebral, spinal, or retinal infarction. (Note: Evidence of CNS infarction is defined above.)

Definition of silent CNS infarction: Imaging or neuropathological evidence of CNS infarction, without a history of acute neurological dysfunction attributable to the lesion.

Definition of intracerebral hemorrhage: A focal collection of blood within the brain parenchyma or ventricular system that is not caused by trauma. (Note: Intracerebral hemorrhage includes parenchymal hemorrhages after CNS infarction, types I and II-see "Hemorrhagic Infarction.")

Definition of stroke caused by intracerebral hemorrhage: Rapidly developing clinical signs of neurological dysfunction attributable to a focal collection of blood within the brain parenchyma or ventricular system that is not caused by trauma.

Definition of silent cerebral hemorrhage: A focal collection of chronic blood products within the brain parenchyma, subarachnoid space, or ventricular system on neuroimaging or neuropathological examination that is not caused by trauma and without a history of acute neurological dysfunction attributable to the lesion.

Definition of subarachnoid hemorrhage: Bleeding into the subarachnoid space (the space between the arachnoid membrane and the pia mater of the brain or spinal cord).

Pathologic types of stroke

Stroke is classified into two major types:

• Ischemic due to thrombosis, embolism, or systemic hypoperfusion
• Hemorrhagic due to intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH)

TOAST Classification of Ischemic Stroke

• Large-artery atherosclerosis: Involves thrombotic in situ occlusions on atherosclerotic lesions in the carotid, vertebrobasilar, and cerebral arteries, typically proximal to major branches. NOTE: Large-artery infarctions may also be cardioembolic.
• Cardioembolic Infarction: Cardiogenic emboli are a common source of recurrent stroke. They may account for up to 20% of acute strokes.
• Small-vessel or Lacunar Stroke: Associated with small focal areas of ischemia (usually <1.5cm) due to obstruction of single small vessels, typically in deep penetrating arteries, that generate a specific vascular pathology.
• Stroke of other determined etiology
• Stroke of undetermined etiology

Global Stroke Statistics

• Globally, stroke remains the second leading cause of death (11.6% of total deaths) and the third-leading cause of death and disability combined (5.7%).
• From 1990 to 2019:
  • The absolute number of incident strokes increased by 70.0% (67.0–73.0).
  • Prevalent strokes increased by 85.0%.
  • Deaths from stroke increased by 43.0%.
  • DALYs (Disability-Adjusted Life Years) due to stroke increased by 32.0%.
• In 2019, there were:
  • 12.2 million incident cases of stroke.
  • 101 million prevalent cases of stroke.
  • 143 million DALYs due to stroke.
  • 6.55 million deaths from stroke.

Stroke Epidemiology in AFRICA

• Prevalence: 58-316/100,000
• Prevalence increases with age
• Incidence: 26-319/100,000

Hospital data:

• 0.9 - 4.9% of hospital admissions
• 6.5 - 68% of neurological admissions
• 2.8-8.4% of hospital deaths

• Case fatality rate averages 35%, ranges from 14.9% to 77% (ICH)

• Non-modifiable Risk Factors
• Modifiable Risk Factors

Non-modifiable Risk Factors

• Age
• Sex
• Race/ethnicity
• Heredity (Family history of stroke)
• History of Migraine headache

Modifiable Risk Factors

• Hypertension
• Obesity
• Cigarette smoking
• Alcohol consumption
• Dyslipidemia
• Diabetes mellitus

Dominant Modifiable Risk Factors for Stroke among Africans in the SIREN Study

• Baseline age ≥50 years
• Education (some vs none)
• Monthly income > US$100
• Hypertension
• Dyslipidemia
• Diabetes
• Cardiac disease
• Elevated waist-to-hip ratio
• Physical inactivity
• Current cigarette smoker
• Stress
• Family history of CVD (Cardiovascular Disease)
• Added salt at the table
• Low green leafy vegetable consumption
• Regular sugar consumption
• Regular meat consumption
• Composite PAR (Population Attributable Risk)

Risk Factors for aSAH (Aneurysmal Subarachnoid Hemorrhage)

• Female Sex
• Hypertension
• Smoking
• Alcohol abuse
• Use of sympathomimetic drugs (e.g., cocaine)
• Presence of an unruptured cerebral aneurysm (particularly those that are symptomatic, larger in size, and located either on the posterior communicating artery or the vertebrobasilar system)
• History of previous aSAH (with or without a residual untreated aneurysm)
• History of familial aneurysms (at least 1 first-degree family member with an intracranial aneurysm, and especially if ≥2 first-degree relatives are affected)
• Family history of aSAH
• Certain genetic syndromes, such as autosomal dominant polycystic kidney disease and type IV Ehlers-Danlos syndrome

Etiology Of Ischemic Stroke

LARGE VESSEL EMBOLIC:

• The Heart
• Valve diseases
• Atrial Fibrillation
• Dilated cardiomyopathy
• Myxoma
• Arterial Circulation (artery to artery emboli)
• Atherosclerosis of carotids
• Arterial dissection
• Vasculitis
• The Venous Circulation
• PFO with R to L shunt
• Emboli

SMALL VESSEL [Lacunes (<1.5cm)]

Risk Factors

• HTN
• Dyslipidaemia
• DM
• Tobacco Use
• Sleep apnea

Etiology of ICH

• Traumatic
• Spontaneous
• Hypertensive
• Amyloid angiopathy
• Aneurysmal rupture
• Arteriovenous malformation rupture
• Bleeding into tumor
• Cocaine and amphetamine use

Pathophysiology of Ischaemic Stroke

• Vessel occlusion
• Failure of energy production
• Anaerobic glycolysis and lactic acidosis
• Failure of the ion pumps
• Neuronal depolarization and intracellular calcium overload.
• Release of neurotoxic substances such as:
• Excitatory neurotransmitters (chiefly glutamate)
• Inflammatory mediators (eg. prostaglandins, leukotrienes)
• Free radicals (eg. nitric oxide)
• Activated lytic enzymes (lipases, proteases)
• Neuronal death

• Ischaemic damage depends on the degree and the duration of ischaemia.
• Following complete occlusion of a vessel, a central core of densely ischaemic tissue is irreversibly damaged (infarction) within minutes.

Major Stroke Syndromes

• All Occur Suddenly
• Left (dominant) cerebral hemisphere
• Right (nondominant) cerebral hemisphere
• Brainstem
• Cerebellum

Note: The dominant cerebral hemisphere is the side that controls language function.

Left (Dominant) Cerebral Hemisphere

• Aphasia
• L gaze preference
• R visual field deficit
• R hemiparesis
• R hemisensory loss

Right (Nondominant) Cerebral Hemisphere

• Neglect (= L hemi-inattention)
• R gaze preference
• L visual field deficit
• L hemiparesis
• L hemisensory loss

Brainstem

• Hemi- or quadriparesis
• Sensory loss in hemibody or all 4 limbs
• Crossed signs (face 1 side, body other side)
• Diplopia, dysconjugate gaze
• Vertigo, tinnitus
• Nausea, vomiting
• Hiccups, abnormal respirations
• Decreased consciousness

Cerebellum

• Truncal ataxia
• Gait ataxia
• Limb ataxia

Hypertensive ICH

Spontaneous rupture of a small artery deep in the brain

Typical sites:

• Posterior limb of the internal capsule
• Basal Ganglia (Putamen)
• Pons
• Thalamus
• Cerebellum

Typical clinical presentation:

• Patient is typically awake and often stressed, then abrupt onset of symptoms with acute decompensation

Ganglionic Bleed

• Contralateral hemiparesis
• Hemisensory loss
• Homonymous hemianopia
• Conjugate deviation of eyes toward the side of the bleed or downward
• Altered mental status (stupor, coma)

Cerebellar Hemorrhage

• Vomiting
• Ataxia
• Eye deviation toward the opposite side of the bleed
• Small sluggish pupils
• Altered mental status

Pontine Hemorrhage

• Pin-point but reactive pupils
• Abrupt onset of coma
• Decerebrate posturing or flaccidity
• Ataxic breathing pattern

Subarachnoid Hemorrhage

• "Worst headache of my life"
• Altered mental status
• Photophobia
• Nuchal rigidity
• Seizures
• Nausea and vomiting

History

A focused medical history aims to identify risk factors:

• Hypertension
• Diabetes mellitus
• Tobacco use
• Dyslipidemia
• History of coronary artery disease, coronary artery bypass, or atrial fibrillation

In addition to the above, in younger patients, elicit a history of:

• Coagulopathies
• Illicit drug use (especially cocaine)
• Migraines
• Oral contraceptive use

Common Symptoms and Signs

Abrupt onset of:

• Hemiparesis, monoparesis, or (rarely) quadriparesis
• Hemisensory deficits
• Monocular or binocular visual loss
• Visual field deficits
• Diplopia
• Dysarthria
• Facial droop
• Ataxia
• Vertigo (rarely in isolation)
• Aphasia
• Sudden decrease in the level of consciousness

Physical Examination

The goals of the physical examination are:

• Detection of extracranial causes of stroke symptoms
• Distinguish stroke from stroke mimics
• Determine and document for future comparison, the degree of neurologic deficit (NIH Stroke Scale)
• Localize the lesion
• Identify comorbidities
• Identify conditions that may influence treatment decisions (e.g., recent surgery or trauma, active bleeding, active infection)

• Space occupying lesion (tumor, infection/abscess, Epidural, Subdural Hematomas)
• Seizures
• Hypoglycemia
• Migraine
• Syncope
• Labyrinthine disorders

Mandatory Tests for All Patients with Suspected Stroke:

1. Noncontrast brain CT or brain MRI
2. Finger stick blood glucose - random blood glucose
3. Oxygen saturation

Additional Immediate Tests for Ischemic and Hemorrhagic Stroke:

• Electrocardiogram
• Full blood count including platelets
• Troponin
• Prothrombin time and international normalized ratio (INR)
• Activated partial thromboplastin time
• Coagulation status- Clotting time, thrombin time, or appropriate direct factor Xa activity assay if on direct thrombin inhibitor or direct factor Xa inhibitor and candidate for thrombolytic therapy with alteplase

Considerations for Thrombolytic Therapy:

• Thrombolytic therapy should not be delayed for hematologic studies except for anticoagulant history or suspicion of bleeding abnormality or thrombocytopenia.
• Mandatory pre-thrombolytic therapy: Blood glucose

Additional Laboratory Studies Appropriate for Selected Patients:

• Serum electrolytes, urea nitrogen, creatinine
• Fasting lipid profile
• Liver function tests
• Toxicology screen
• Blood alcohol level
• Pregnancy test in women of child-bearing potential
• Arterial blood gas if hypoxia suspected
• Chest radiograph if lung disease suspected
• Lumbar puncture if subarachnoid hemorrhage suspected and head CT scan negative for blood (Note: precludes tPA administration)
• Electroencephalogram if seizures suspected

Note: Individual patient evaluation may warrant additional or fewer tests based on clinical presentation and suspicion.

Additional Tests and Considerations for Stroke Evaluation:

If Fever is Present:

• Chest radiography
• Urinalysis
• Blood cultures

For Potential Coagulopathy Reversal:

• Blood for type and cross-match in case fresh frozen plasma is needed

Dosage Accuracy Considerations:

• Obtain accurate body weight early during urgent evaluation to limit medication dosage errors, especially with alteplase.

Neuroimaging:

• Necessary to exclude hemorrhage as a cause of deficit and assess brain injury.
• Advanced CT and MRI technologies may distinguish irreversibly infarcted tissue from salvageable tissue, aiding patient selection for therapy.

Cardiac Studies:

• Electrocardiography (ECG) important for detecting possible concurrent acute cardiac ischemia.
• Stroke alone can lead to ECG changes due to sympathetic response or centrally mediated effects.
• Cardiac monitoring for at least 24 hours post-stroke to detect chronic or intermittent arrhythmias, especially atrial fibrillation.
• Extended cardiac event monitoring may increase detection of occult atrial fibrillation and reduce the risk of recurrent stroke.
• Transthoracic and transesophageal echocardiography can detect cardiogenic and aortic sources for embolism but may be postponed to later hospitalization, except in cases with suspicion of endocarditis.

General Management of Acute Stroke Patient

• Support of vital functions and prevention of general complications
• Airway support and ventilation
• Cardiac monitoring and care
• Prevention of water and electrolyte abnormalities
• Maintenance of adequate nutritional status
• Control of blood glucose
• Blood pressure monitoring
• Use of antiplatelets (AIS)
• Use of statins (AIS vs ICH)
• Frequent position changes to prevent bed sores and muscle contractures
• Early physical therapy and rehabilitation
• Urinary care
• Control of fever and early diagnosis and treatment of infections
• Use of sedation

Treatment of Acute Neurological Complications

• Cerebral edema and increased intracranial pressure
• Seizures

Deep Vein Thrombosis (DVT) Prophylaxis:

• Peak incidence of DVT is within the first week after stroke.
• Peak incidence of pulmonary embolism is 2–4 weeks after stroke.
• Use of Intermittent Pneumatic Compression Device for DVT prophylaxis.
• Usually safe to start subcutaneous heparin 24 hours after tPA.

Fever:

• Elevated temperatures (>37.5°C) worsen outcomes. Treat with acetaminophen and/or cooling blankets.

Hyperglycemia (>140 mg/dL):

• Promotes anaerobic metabolism and lactic acidosis in ischemic tissue. This leads to increased risk of hemorrhage, especially after thrombolysis, and increased morbidity.

Management of Fluid Status:

• Use isotonic crystalloids (normal saline).
• Hypotonic fluids should be avoided as they can potentially worsen cerebral edema.

Seizures:

• Occur within the first week of stroke in 2–6% of patients.
• Seizure can also occur at stroke onset in <5% of patients.
• More common with cortical strokes and higher stroke severity.
• Most common are simple partial seizures.
• Treat with anti-seizure medications.
• Use caution with IV anti-seizure medications as some can cause hypotension when given as bolus (phenytoin).
• Do EEG to rule out non-convulsive seizures.

Cerebral Edema and Increased Intracranial Pressure:

• Monitor for signs of cerebral edema and intervene as appropriate.

Management of Ischaemic Stroke

• Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is the only approved and causal therapy for acute ischemic stroke.
• Benefit is extremely time sensitive.
• Before rt-PA can be administered, a complex diagnostic workup, including neurological examination, imaging studies, and laboratory tests, is necessary to exclude hemorrhage or other contraindications to rt-PA therapy.

tPA Fast Facts

• Tissue plasminogen activator
• "Clot buster"
• IV tPA window 3 hours
• IA tPA window 4.5 hours
• Disability risk decreases by 30% despite ~5% symptomatic ICH risk
• Contraindications:
• Hemorrhage
• SBP > 185 or DBP > 110
• Recent surgery, trauma, or stroke
• Coagulopathy
• Seizure at onset of symptoms
• NIHSS > 21
• Glucose < 50 mg/dl

Blood Pressure Management

• BP Management
• The goal is to maintain cerebral perfusion!!
• CPP = MAP - ICP (needs to be at least 70 mmHg)
• Higher BP goals with Ischemic stroke
• Lower BP goals with Hemorrhagic stroke (avoid hemorrhagic expansion, especially in AVMs and aneurysms)

BP-AIS Relationship

• BP increase is due to arterial occlusion (i.e., an effort to perfuse penumbra)
• Failure to recanalize (with or without thrombolytic therapy) results in high BP and poor neurological outcomes
• Lowering BP starves penumbra, worsens outcomes

Supportive Therapy

• Glucose Management
• Infarction size and edema increase with acute and chronic hyperglycemia
• Hyperglycemia is an independent risk factor for hemorrhage when stroke is treated with t-PA
• Antiepileptic Drugs
• Seizures are common after hemorrhagic CVAs
• ICH-related seizures are generally non-convulsive and are associated with higher NIHSS scores, a midline shift, and tend to predict poorer outcomes

Management of Haemorrhagic Stroke

• No specific evidence-based treatment
• Management largely supportive
• Active management of BP to reduce hematoma expansion and worse outcome (INTERACT study)

Blood Pressure in Haemorrhagic Stroke

For ICH patients presenting with SBP between 150 and 220 mm Hg and without contraindication to acute BP treatment, acute lowering of SBP to 140 mm Hg is safe (Class I; Level of Evidence A) and can be effective for improving functional outcome (Class IIa; Level of Evidence B).

Surgical Treatment of ICH

• Patients with cerebellar hemorrhage who are deteriorating neurologically or who have brainstem compression and/or hydrocephalus from ventricular obstruction should undergo surgical removal of the hemorrhage as soon as possible (Class I; Level of Evidence B).

INTERACT3 Care Bundle for Acute sICH

Components of the Care Bundle: Management of Hypertension, Hyperglycemia, Fever, Reversal of anticoagulation

Interpretation of INTERACT3 Results

• Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral hemorrhage.
• Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition.

Rehabilitation and Recovery

Given the potentially serious nature and complex pattern of evolving disability and the increasing evidence for efficacy, it is recommended that all patients with stroke have access to multidisciplinary rehabilitation.

Stroke Unit Care

• Patients receive the best treatment
• Outcome is better
• Challenges of establishing a stroke unit are numerous, but surmountable.

Concept of Stroke Teams & Stroke Units

• "Time is brain"
• Stroke awareness
• Common mistakes may lead to fatal consequences
• "Boutique stroke neurology": Patients will receive the best care; length of stay shortened

Stroke Prevention

• Take care of identified modifiable or potentially modifiable risk factors

1. Blood Pressure Management:

   • Management protocols vary based on individual patient factors.

   • Acute Ischemic Stroke:

     • Avoid lowering blood pressure acutely unless extreme hypertension or specific indications present.
     • Elevated blood pressure may be necessary to maintain brain perfusion in ischemic areas.

   • Interventions:

     • Observational studies suggest adverse effects of reducing blood pressure in the first 24 hours post-stroke.
     • Limited evidence from trials does not support the benefits of early blood pressure reduction in acute ischemic stroke.

   • Thrombolytic Therapy:

     • Blood pressure should be ≤185/110 mmHg before thrombolytic therapy.
     • Maintain ≤180/105 mmHg for at least 24 hours post-treatment.

   • Acute Hemorrhagic Stroke:

     • Approach to blood pressure management varies based on potential benefits and risks.

   • Choice of Antihypertensive Agent:

     • Intravenous agents preferred for precise blood pressure control.
     • First-line options: labetalol, nicardipine, clevidipine.
     • Nitroprusside considered second-line due to added risks.
     • Avoid medications associated with rapid or precipitous blood pressure decline.

2. Fluid Management:

   • Intravascular Volume Depletion:

     • Common in acute stroke, especially in older adults.
     • May worsen cerebral blood flow.

   • Fluid Choice:

     • Isotonic saline without dextrose preferred for intravascular fluid repletion and maintenance therapy.
     • Avoid excess free water (e.g., ½ isotonic saline) to prevent exacerbation of cerebral edema.
     • Fluids containing glucose should be avoided to prevent exacerbation of hyperglycemia.

   • Individualized Approach:

     • Fluid management must be tailored to the patient's cardiovascular status, electrolyte disturbances, and other factors affecting fluid balance.

   • Hyponatremia in Subarachnoid Hemorrhage:

     • Hyponatremia following subarachnoid hemorrhage may result from inappropriate secretion of antidiuretic hormone (SIADH) or cerebral salt-wasting.
     • Treatment strategies vary based on the underlying cause, as they are physiologically distinct.

3. Hypoglycemia:

   • Check blood sugar and correct low serum glucose promptly ( < 60 mg /dL [3.3 mmol/L]).

4. Hyperglycemia:

   • Treat severe hyperglycemia in acute stroke to achieve serum glucose concentrations in the range of 140 to 180 mg/dL (7.8 to 10 mmol/L).
   • Consider tight glucose control with intravenous insulin.

5. Swallowing Assessment:

   • Assess swallowing function before administering oral medications or food.
   • Maintain NPO status until swallowing function is evaluated to prevent aspiration.

6. Head and Body Position:

   • Keep the head in neutral alignment with the body.
   • Elevate the head of the bed to 30 degrees for patients in the acute phase of stroke who are at risk for:
     • Elevated intracranial pressure:
       • Intracerebral hemorrhage.
       • Cerebral edema >24 hours from stroke onset in patients with large ischemic infarction.
     • Aspiration:
       • Patients with dysphagia and/or diminished consciousness.
     • Cardiopulmonary decompensation or oxygen desaturation:
       • Patients with chronic cardiac and pulmonary disease.

7. Fever:

   • Investigate and treat the source of fever promptly.
   • Antipyretics may be used to lower temperature.
   • Maintain normothermia for at least the first several days after acute stroke, although the clinical utility of this approach is uncertain.

8. Stroke Unit Care:

   • Admit patients to specialized stroke units for better outcomes.

Common Acute and Subacute Medical Problems Associated with Stroke:

• Myocardial infarction
• Heart failure
• Dysphagia
• Aspiration pneumonia
• Urinary tract infection
• Deep vein thrombosis
• Pulmonary embolism
• Dehydration
• Malnutrition
• Pressure sores
• Orthopedic complications and contractures