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Nervous system

Stroke

Cerebrovascular accident (CVA) or stroke, is an emergency medical condition characterized by an acute compromise of the cerebral perfusion or vasculature.


Epidemiology

Stroke is ranked as the second leading cause of death worldwide with an annual mortality rate of about 5.5 million

(a) Global distribution of stroke mortality rates. (b) Global distribution of DALY loss due to stroke | Johnston S. C., Mendis S., Mathers C. D. Global variation in stroke burden and mortality: estimates from monitoring, surveillance, and modelling. The Lancet Neurology. 2009;8(4):345–354. doi: 10.1016/S1474-4422(09)70023-7.

Etiopathogenesis

Modifiable risk factors:

  • Hypertension
  • Diabetes mellitus
  • High blood cholesterol
  • Cardiovascular diseases
  • Atrial fibrillation (AFib)
  • Sedentary lifestyle
  • Smoking and alcohol consumption

Nonmodifiable risk factors:

  • Age: strongest determinant of stroke and the risk of stroke doubles every decade above age 55
  • Gender

Genetic risk factors:

Conventional risk factors such as hypertension fail to explain all stroke risk, and there is increasing evidence for the potential pathophysiological role of genes in stroke
  • Apolipoprotein E (APOE)
  • Methylenetetrahydrofolate reductase (MTHFR)
  • Endothelial Nitric Oxide Synthase (ENOS)
  • Factor V Leiden (F5)
  • Cytochrome P450 4F2 (CYP4F2)
  • Beta-fibrinogen
  • Phosphodiesterase 4D (PDE4D)

Hypertension:

M/C modifiable risk factor for stroke. Chronic uncontrolled hypertension causes small vessel strokes mainly in the internal capsule, thalamus, pons, and cerebellum.

Alcohol:

Alcohol intake has a J-shaped relationship with ischemic stroke. Alcohol intake increases the risk of hemorrhagic stroke in a near linear relationship.
  • Mild-to-moderate drinking: Lower risk of ischemic stroke
  • Heavy drinking: Drastically increased risk of ischemic stroke
Stroke Pathogenesis
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Ischemic stroke

Interruption of blood supply to a part of brain resulting in sudden loss of function

Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria:

Most widely used subclassification criteria for ischaemic stroke which is grouped into five main pathological or etiological types
  • Large artery thrombotic stroke (20%): Atherosclerotic plaques in the large blood vessels of the brain lead to ischemia and infarction
  • Small penetrating artery thrombotic stroke (Lacunar stroke) (25%): One or more vessels in the brain affected (microatheromatosis)
  • Cardiogenic embolic stroke (15%): Associated with cardiac dysrhythmias, valvular heart disease, and thrombi in the left ventricles
  • Cryptogenic strokes (5-10%): Cause is unknown
  • Strokes associated with other causes (20-25%): Such as illicit drug use
Ischemic Stroke Pathogenesis

Haemorrhagic stroke

Rupture of a blood vessel or an abnormal vascular structure

  • Intracerebral haemorrhage (ICH): M/C type of nontraumatic ICH and accounts for 80% of haemorrhagic stroke and 10-15% of all strokes
    • Mostly caused by uncontrolled hypertension leading to rupture of small vessels. The rupture leads to an avalanche type effect with breakage of nearby vessels resulting in haematoma expansion in up to 40% of cases.
  • Subarachnoid haemorrhage (SAH) (5% of all strokes): Mainly due to saccular aneurysms though it is also associated with arteriovenous malformation, intracranial neoplasm, and some medications such as anticoagulants. About 65% of subarachnoid haemorrhage patients survive, but half remain disabled primarily due to severe cognitive deficit.
Hemorrhagic Stroke Pathogenesis

Complications:

Complications after a stroke include worsening neurological status from the extension of the stroke or hemorrhagic conversion and a multitude of other complications associated with prolonged immobility and hospitalization.
  • Recurrent stroke – 9%
  • Epileptic seizure – 3%
  • Urinary tract infection – 24%
  • Pneumonia – 22%
  • Pressure sores – 21%
  • Deep venous thrombosis – 2%
  • Pulmonary embolism – 1%
  • Depression – 16%
  • Anxiety – 14%
Non-neural complications of stroke
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Presentation

Early stroke symptoms: ACT FAST

American Stroke Association acronym to recognize the early symptoms of a stroke. They include:
  • F (Face) – A droop or an uneven smile on a person’s face.
  • A (Arms) – Arm numbness or weakness – Elicited by asking the patient to lift the arms
  • S (Speech difficulty) – Slurred speech or difficulty in understanding speech
  • T (Time) – If any of the above features are present, even if transient, it is time to call the emergency helpline (911).
The components of "FAST" campaign by the American Hearts Association
The components of “FAST” campaign by the American Hearts Association

National Institutes of Health Stroke Scale (NIHSS):

Most commonly used scale to measure the severity of the stroke and has 11 categories and a score that ranges from 0 to 42. The 11 categories include the level of consciousness (LOC), which incorporates LOC questions evaluating best gaze, visual, facial palsy, motor arm, motor leg, limb ataxia, sensory, best language, dysarthria, and extinction and inattention.
  • 0: No stroke
  • 1-4: Minor stroke
  • 5-15: Moderate stroke
  • 16-20: Moderate-to-severe stroke
  • 21-42: Severe stroke

Localization of stroke

Ischemic Stroke Impairment by Localization

Cortical & subcortical “Lacunar” strokes:

Brainstem strokes:


Diagnosis

The initial workup of a stroke patient involves stabilizing the Airway, Breathing, and Circulation (ABC). This is followed by a rapid, concise, history and exam such as the NIHSS which is administered simultaneously as the patient gets IV access, telemetry, and labs were drawn.

Labs:

All patients suspected of having an acute ischemic stroke should be admitted for a full neurological workup.  Neurology consultation should be obtained. The workup of acute ischemic stroke includes a search for a source of thrombus, which includes carotid artery evaluation by ultrasound, CTA, MRA, or conventional angiography.  A transthoracic echocardiogram is obtained to ascertain for low ejection fraction, the cardiac source of the clot, or patent foramen ovale.  EKG and telemetry are obtained to ascertain for rhythms predisposing to stroke such as atrial fibrillation.  Labs such as a fasting lipid panel, and hemoglobin A1C, are obtained to ascertain for modifiable risk factors for stroke.  Other labs such as a hypercoagulable panel in young patients or B12 and syphilis testing in selected patients is also obtained.
  • Basic metabolic panel (BMP)
  • Complete blood count (CBC)
  • Cardiac markers
  • Coagulation profile: prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (aPTT)
  • Lipid Panel
  • Hemoglobin A1C

Non-contrasted head computed tomogram (CT)

  • Earliest sign: Hyperdense vessel segment (direct visualization of intravascular thrombus/embolus)  – most often seen in the MCA (hyperdense MCA sign and MCA dot sign)

CT perfusion scan:

  • Infarct core: Matched defects in cerebral blood volume (CBV) and mean transit time (MTT)
  • Ischemic penumbra: Prolonged MTT, but preserved CBV

Magnetic resonance imaging (MRI) scan:

  • Early hyperacute: Increased diffusion-weighted image (DWI) signal and reduced apparent diffusion coefficient (ADC) values
  • Late hyperacute (>6 hours): High T2 signal in fluid-attenuated inversion recovery (FLAIR) image

Differential diagnosis:

‘Structural stroke’ mimics:

  • Primary cerebral tumours
  • Metastatic cerebral tumours
  • Subdural haematoma
  • Cerebral abscess
  • Peripheral nerve lesions
  • Vascular or compressive
  • Demyelination

‘Functional stroke’ mimics:

  • Todd’s paresis: After epileptic seizure
  • Hypoglycemia
  • Migranous aura ± headache
  • Focal seizures
  • Ménière’s disease
  • Conversion disorder
  • Ecephalitis
FeatureStrokeStroke mimic
Symptom onsetSudden (minutes)Slower
Symptom progressionRapidSlower
Severity of deficitUnequivocalVariable
Pattern of deficitHemispheric patternNon-specific
(with confusion, memory loss, balance disturbance)
Loss of consciousnessUncommonCommon

Management

Stroke prevention, either primary or secondary is the primary goal of treatment. Patients at the highest risk should be identified early and counseled on lifestyle changes as well as control of comorbid conditions to prevent this devastating outcome.

Stroke therapy: This represents the overall process to manage the incidence of stroke.
Stroke therapy: This represents the overall process to manage the incidence of stroke. | Kuriakose, D., & Xiao, Z. (2020). Pathophysiology and Treatment of Stroke: Present Status and Future Perspectives. International journal of molecular sciences, 21(20), 7609. https://doi.org/10.3390/ijms21207609

Acute stroke management

Time is brain!

Speed of treatment is a critical factor in determining the outcome of thrombolytic and/or endovascular treatment for patients with disabling acute ischemic stroke.

Acute ischemic stroke:

I. Intravenous thrombolytics (IVT): Promote fibrinolysin formation, which catalyzes the dissolution of the clot blocking the cerebral vessel.

  • Fibrin activators (convert plasminogen to plasmin directly):
    • Alteplase aka. recombinant tissue plasminogen activator (rt-PA): M/effective IVT drug
    • Reteplase
    • Tenecteplase
  • Non-fibrin activators (indirectly convert plasminogen to plasmin):
    • Streptokinase
    • Staphylokinase

II. Fibrinogen-depleting agents: Decrease blood plasma levels of fibrinogen, hence reduce blood thickness and increase blood flow. They also remove the blood clot in the artery and restore blood flow in the affected regions of the brain.

  • Defibrinogenating agent: Ancrod (derived from snake venom) that has been studied for its ability to treat ischemic stroke within three hours of onset

III. Antiplatelet therapy: Acute ischemic stroke management and for prevention of stroke incidence. It is also vital in controlling non-cardioembolic ischemic stroke and TIA.

  • Antiplatelet agents: Aspirin, clopidogrel and ticagrelor (within the first few days of attack)
  • Dual antiplatelet therapy (more effective): Combination of clopidogrel/prasugrel/ticagrelor + aspirin (most beneficial if introduced within 24 h of stroke and continued for 4–12 weeks)

Acute hemorrhagic stroke:

I. BP management: BP should be reduced gradually to 150/90mmHg. BP should be checked every 10-15 minutes.

  • β-blockers: Labetalol, esmolol
  • ACE inhibitor: Enalapril
  • Calcium channel blockers: Nicardipine or hydralazine

II. Raised ICP:

  • Elevating head of bed to 30°
  • Osmotic agents: Mannitol, hypertonic saline
  • Hyperventilation after intubation & sedation

III. Hemostatic Therapy: Reduce the progression of hematoma and to reverse the coagulopathy in patients taking anticoagulants.

  • Thrombocytopenia: Platelet concentrate
  • Elevated PT-INR: IV vitamin K and FFP or PCCs

IV: Surgery

  • Craniotomy
  • Decompressive craniectomy
  • Stereotactic aspiration
  • Endoscopic aspiration
  • Catheter aspiration

Long-term neuroprotective treatment

Antihypertensive therapy:

Hypertension is the biggest risk factor for stroke.

Stem cell therapy:

It offers promising therapeutic opportunities, safety and efficacy to stroke patients. Stem cell therapy enhances the proliferation of neural stem cells and neuritogenesis
  • Multilineage differentiating stress-enduring (Muse) cells: New type of mesenchymal stem cells (MSCs) found in connective tissue.

Neural repair:

Alternative therapy to neuroprotection. It is used to rejuvenate the tissue when the damage is already done and is therefore not time-bound but is most effective when administered 24 h after stroke attack.
  • Neural repair utilizes stem cell therapy to initiate repair mechanisms through cell integration into the wound or use of neurotrophic factors to block neuronal growth inhibitors. These cells may be channeled to any injured region to facilitate greater synaptic connectivity.
TreatmentTarget group
Antiplatelet Drugs
(Clopidogrel, Aspirin/Dipyridamole)
Ischaemic stroke or TIA (in sinus rhythm)
Statins
Ischaemic stroke or TIA
BP lowering
(ACE-inhibitors, Thiazide diuretics, other agents)
All stroke (Ischaemic or haemorrhagic) with BP > 130/80 mm-Hg
AnticoagulationIschaemic stroke with atrial fibrillation
Carotid endarterectomyIschaemic stroke or TIA
Recently severe symptomatic carotid stenosis

Rehabilitation:

Stroke can leave individuals with short- and long-term disabilities. Daily activities like walking and toileting are often affected, and sensorimotor and visual impairment are common. Rehabilitation aims to reinforce the functional independence of people affected by stroke. It includes working with patients and families to provide supportive services and post-stroke guidance after 48 h of stroke attack in stable patients.
  • Physical, occupational, speech and/or cognitive therapy: Assist patients to recover problem-solving skills, access social and psychological support, improve their mobility and achieve independent living.
  • Task-oriented approaches, like arm training and walking, help stroke patients to manage their physical disability, and visual computer-assisted gaming activities have been used to enhance visuomotor neuronal plasticity [160].

Lifestyle modifications:

Healthy lifestyle related practices for improved cardiovascular health
Healthy lifestyle related practices for improved cardiovascular health | DASH: Dietary Approaches to Stop Hypertension; AHA: American Heart Association; USDA: United States Department of Agriculture | Suk SH, Sacco RL, Boden-Albala B, Cheun JF, Pittman JG, Elkind MS, et al. Abdominal obesity and risk of ischemic stroke: The northern manhattan stroke study. Stroke; a journal of cerebral circulation. 2003;34:1586–1592. | Walker SP, Rimm EB, Ascherio A, Kawachi I, Stampfer MJ, Willett WC. Body size and fat distribution as predictors of stroke among us men. Am J Epidemiol. 1996;144:1143–1150.

Summary

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