History and exam
Key diagnostic factors
common
vision loss or visual field deficit
Monocular vision loss may occur and is often transient.[118] This is a common early warning signal for cervical carotid stenosis. It can present as amaurosis fugax or retinal stroke (branch or central retinal artery occlusion); recognize and investigate with the same urgency.
Vision loss may occur in patients with posterior circulation ischemia.
When visual field loss is unilateral, this sign may reflect either carotid or vertebrobasilar ischemia, whereas bilateral visual field loss is usually due to vertebrobasilar ischemia.
Visual symptoms may occur in cerebral venous sinus thrombosis due to increased intracranial pressure related to transient visual obscurations or vision loss, papilledema, and diplopia.[8]
weakness
Complete or partial loss of muscle strength in face, arm, and/or leg is a typical presentation of stroke.
Weakness of all three suggests deep hemispheric involvement, although this may not differentiate stroke mechanism.
As with most stroke signs and symptoms, bilateral involvement is uncommon and may reflect alternative etiologies.
Hemiparesis is associated with lacunar strokes.
aphasia
Impairment in any language function, either expressive or receptive, is a sign of dominant hemispheric ischemia. Patients may present with different types or patterns of aphasia that correspond to the location of lesions.
ataxia (impaired coordination)
In the absence of muscle weakness, ataxia points to ischemia involving the cerebellum or its connections with the rest of the brain.
Posterior circulation strokes are more commonly associated with difficulty with fine motor coordination and gait.
Other diagnostic factors
common
history of transient ischemic attack (TIA)
More than half of patients presenting with stroke related to a cervical carotid artery atherosclerosis have a history of TIA. Conversely, patients with a history of TIA are at a significant risk of subsequent stroke. Most of these strokes occur within days of the TIA; a pooled analysis showed that 5% of TIA patients have a stroke within 2 days.[134]
sudden onset of symptoms
Stroke symptoms often start suddenly over seconds to minutes and may worsen in a stepwise fashion, fluctuate, or stutter.
Slowly progressive symptoms often reflect other etiologies, such as intracerebral hemorrhage. Symptoms in patients with cerebral venous thrombosis tend to occur more insidiously than in other stroke types, and the majority will present >48 hours after onset.[8]
It is important to differentiate multiple, stepwise worsening from a gradual decline.
negative symptoms (i.e., loss of function)
Stroke often presents with negative symptoms such as visual loss, numbness, or weakness.
Positive symptoms such as marching paresthesias, visual hallucinations, and abnormal motor manifestations are more likely to be related to complicated migraine or seizure. There are occasional exceptions: for example, neuralgia is one of the most common symptoms in patients with thalamic infarction.
altered sensation
Patients often describe sensory loss and paresthesias as numbness.
headache
Although headache is not uncommon in acute stroke, it should alert the physician to the possibility of other pathologies such as intracerebral hemorrhage (may be insidious and gradually increasing), subarachnoid hemorrhage (sudden onset with gradual moderation, "most severe headache of my life"), intracranial hypertension (which may be caused by cerebral venous sinus thrombosis, space-occupying lesion), or complicated migraine.[8]
diplopia
May occur in patients with posterior circulation ischemia.
sensory loss
Unilateral sensory loss on neurologic exam may involve some or all primary modalities. Patients may report loss of sense of vibratory, pressure, and touch stimuli, or that they cannot feel pain or temperature.
Cortical sensory loss usually impairs fine sensory processing abilities such as 2-point discrimination, graphesthesia, or stereognosis.
dysarthria
This sign may accompany facial, tongue, and pharyngeal muscle weakness or cerebellar dysfunction, and is usually due to posterior circulation ischemia, but may be due to a lacunar infarct.
"Crossed" syndromes
Posterior circulation strokes are associated with ipsilateral cranial nerves signs and contralateral long motor or sensory tract dysfunction.
gaze paresis
Often horizontal and unidirectional.
More common with anterior circulation strokes.
Wrong-way eye deviation (i.e., gaze deviation away from the side of the brain lesion, toward the hemiparetic side) should prompt consideration of seizure but can also occur with strokes affecting the pons or thalamus.
Horner syndrome suggests ipsilateral carotid dissection.
arrhythmias, murmurs, or pulmonary edema
Associated with cardiac comorbidities, which predispose patients to stroke disease.
Of particular significance is atrial fibrillation, which increases the patient's risk for cardioembolic ischemic stroke. Therefore, all stroke patients should be assessed for this particular cardiac arrhythmia with routine noninvasive monitoring, and in all eligible patients extended monitoring should be offered after stroke to increase the chance of detection of paroxysmal atrial fibrillation and earlier initiation of treatment with anticoagulants.[135]
uncommon
vertigo/dizziness
This is a symptom of posterior circulation ischemia. Although typically reported as a spinning sensation, a feeling like being on a ship in choppy seas also describes vertigo.
It is often associated with nystagmus.
nausea and/or vomiting
This symptom may be due to posterior circulation ischemia, or reflect increased intracranial pressure which may be caused by cerebral venous sinus thrombosis or a space-occupying lesion.[8]
neck or facial pain
May be associated with arterial dissection.
miosis, ptosis, and facial anhidrosis (hemilateral)
Horner syndrome may be associated with posterior circulation strokes, or dissection of carotid artery.
altered level of consciousness/coma
Reduced level of alertness may accompany large anterior circulation, thalamic, bihemispheric, or brain stem strokes. Encephalopathy and coma have been reported in up to 20% of patients with cerebral venous thrombosis.[8]
This sign should prompt a higher level of urgency from both diagnostic (rule out hemorrhage) and management (breathing and airway protection) points of view.
Coma is more common in patients with locked-in syndrome, which indicates brain stem ischemia.
Other conditions mimicking stroke, such as seizures, should be ruled out.
confusion
This is common, especially in older people with previous strokes or cognitive dysfunction.
Receptive (Wernicke) aphasia should be differentiated from confusion because aphasia is a specific sign of dominant-hemisphere ischemia.
Risk factors
strong
hypertension
Hypertension is the single most important risk factor for the development of ischemic and hemorrhagic stroke. Hypertension may contribute to 50% of ischemic strokes.[28]
older age
sickle cell disease
Associated with vascular stenosis, brain ischemia, and Moyamoya disease (vascular occlusion affecting circle of Willis). In children, prophylactic transfusion based on transcranial Doppler ultrasound criteria has been shown to lower subsequent stroke risk.[30]
family history of stroke
Stroke-causing genetic disorders with mendelian inheritance are rare. However, twin studies show that a significant portion of stroke risk is heritable, and epidemiologic studies show that family history of stroke is a risk factor.[10][31]
Numerous candidate genes have been proposed, but none has yet been consistently replicated as a strong risk factor for stroke.[32][33]
Several single-gene causes of ischemic stroke, including CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy), MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), Moyamoya disease, and Fabry disease, are genetically linked to ischemic stroke.[34]
history of transient ischemic attack (TIA)
history of ischemic stroke
History of previous ischemic stroke indicates that the patient may have more ischemic strokes in the future (particularly if risk factors, e.g., hypertension, are not corrected).
cerebral microbleeds
Cerebral microbleeds are associated with an increased risk of ischemic stroke.[37]
smoking
diabetes mellitus
Strongly associated with increased incidence of ischemic stroke.[40]
atrial fibrillation
Strongly implicated in the risk of cardioembolic stroke, but not other ischemic stroke subtypes.[41]
comorbid cardiac conditions
Several cardiac conditions have been reported as potential causes of cardioembolism, with varying degrees of evidence. These include myocardial infarction with regional wall motion abnormalities or decreased left ventricular ejection fraction, valvular disease, mitral valve prolapse, prosthetic heart valve, and cardiomyopathy.[42][43]
carotid artery stenosis
intracranial atherosclerosis (ICAS)
dyslipidemia
Large prospective studies have shown that increased serum total cholesterol is modestly associated with an increased risk of ischemic stroke.[48]
Several studies have confirmed the association of high levels of low-density lipoprotein cholesterol with stroke.[49][50] A meta-analysis showed that increased high-density lipoprotein is protective against ischemic stroke.[51]
weak
ethnicity
Epidemiologic studies indicate ethnic differences in risk of stroke. African-Americans and some Hispanic/Latino American groups have a higher incidence of all stroke types and higher mortality rates than white Americans.[11][12][13][15] Compared with white people, the risk of having a first stroke is nearly twice as high for black people, and black people are twice as likely to die from stroke.[11][52] Higher rates of hypertension, obesity, and diabetes mellitus among black people might account for some of this disparity.[53][54]
poor diet and nutrition
Epidemiologic studies show a relationship between decreased stroke risk and increased consumption of fruits and vegetables, increased consumption of fiber, decreased consumption of sodium, and increased consumption of potassium.[55][56][57][58]
The effects of decreased sodium and increased potassium intake may be mediated by a lower risk of hypertension.[59]
A lower risk of stroke is associated with a diet high in saturated fat in Japanese people.[60]
low birth weight
Low birth weight has been associated with risk of stroke in later life.[61]
physical inactivity
Decreased physical activity has been associated with increased risk of ischemic stroke.[62]
alcohol misuse
estrogen-containing therapy
A small increased risk of ischemic stroke may be present in users of oral contraceptives; however, studies are conflicting.[67][68] Stroke risk in users of oral contraceptives is impacted by several confounding issues, including drug formulation, age, hypertension, smoking, and the presence of migraine with aura.[68]
Clinical trials of oral estrogen or estrogen plus progestogen in postmenopausal women have shown an increased incidence of ischemic stroke.[69][70]
Combined hormonal contraception may further increase the risk of ischemic stroke in women with migraine, specifically migraine with aura.[71]
migraine
severe obstructive sleep apnea
Severe obstructive sleep apnea doubles the risk for incident stroke, especially in young to middle-aged people. Continuous positive airway pressure (CPAP) may reduce stroke risk, but trials have not provided a high level of evidence to support the benefits of CPAP for primary stroke prevention.[75][76]
long sleep duration and poor sleep quality
Long sleep duration (≥9 hours/night), long midday napping (>90 minutes), and poor sleep quality are independently and jointly associated with higher risks of incident stroke.[77]
illicit drug use
Several drugs of abuse may influence stroke risk. Cocaine and other drugs may cause changes in blood pressure or vasculitic-type changes in the intracranial circulation. Methamphetamine use is associated with increased stroke risk in young adults.[78]
Unsafe intravenous injections may lead to infective endocarditis with subsequent cardioembolism, or paradoxical embolism of injected foreign material.
hyperhomocysteinemia
Prospective and case-control studies show that higher serum homocysteine levels are associated with a higher risk of ischemic stroke. However, a randomized trial of homocysteine lowering to prevent stroke showed no benefit of this therapy.[79] Subsequent studies with stroke as a secondary endpoint have shown varying results.[80][81] Therefore, although homocysteine is clearly a marker of ischemic stroke risk, it remains unclear whether homocysteine itself causes stroke.
elevated lipoprotein(a)
Most studies of lipoprotein(a) and ischemic stroke show increased risk with higher lipoprotein(a) levels. Lipoprotein(a) levels can be lowered with niacin. However, in one meta-analysis, niacin did not reduce the risk of ischemic stroke.[82]
hypercoagulable states
Elevated anticardiolipin or anti-beta2-glycoprotein-1 antibody levels have been associated with stroke.
Hereditary conditions associated with venous thromboembolism (e.g., antithrombin III deficiency, protein C deficiency, protein S deficiency, factor V Leiden mutation, or prothrombin gene mutations) have not been found to be risk factors for ischemic stroke, but are related to the risk of cerebral venous sinus thrombosis.[8][42][83]
The possibility that hypercoagulable states may be more strongly associated with certain stroke subgroups, including stroke in young people, is plausible but has not been evaluated in large studies.
elevated C-reactive protein
Associated with an increased risk of stroke after controlling for other risk factors.[84] Whether it directly causes stroke or is merely a marker of risk is uncertain.
aortic arch plaques
patent foramen ovale
A patent foramen ovale (PFO) provides a portal through which a thrombus can pass from the right to the left side of the heart, which could result in an embolus traveling to the brain. Around 25% of the population has a PFO, and in about 80% of patients with PFO and stroke the PFO is incidental, so the direct causal relationship between PFO and stroke is unclear.[87][88] However, PFO is a risk factor in strokes in younger people, especially if the PFO is large, with atrial septal aneurysmal dilation, and has bidirectional flow.[89]
air pollution
Long‐term exposure to air pollution including fine particulate matter (≤2.5 micrometers in aerodynamic diameter [PM2.5]) increases the risk of major cardiovascular disease, all types of strokes, and mortality. Air pollution carries the similar cardiovascular and cerebrovascular risks as hypertension and diabetes and should be considered an important modifiable environmental cardiovascular risk factor.[90]
e-cigarettes
There is growing evidence that e-cigarettes and their aerosol constituents, nicotine, vapourizing solvents, particulate matter, metals, and flavorings may have deleterious effects on the cardiovascular system, respiratory system, and brain.[91] In 2020, >3.6 million adolescents in the US used electronic cigarettes, including 19.6% of young people ages 15-17 years.[91]
Infections (e.g., COVID-19) and vaccine-induced thrombotic thrombocytopenia
Transient provoking factors for cerebral venous thrombosis include infections (COVID-19, head and neck infections).[8][92][93] Vaccine-induced thrombotic thrombocytopenia (VITT) and cerebral venous thrombosis may occur (rarely) days or a few weeks after an individual receives adenovirus-based SARS-CoV-2 vaccines, usually presenting with new onset of headaches and thrombocytopenia.[8][94][95][96] Although cerebral venous thrombosis in VITT is a rare condition, it carries a poor prognosis, with mortality rates ranging from 39% to 61% in initial cohort studies.[8][97] Vaccines remain the most effective means to prevent serious COVID‐19 disease, and their benefits continue to outweigh their risks.[97]
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