Clinical manifestations

Presentation and course

The hallmark of presentation of stroke is its temporal profile, typically characterized by suddenness of onset, with symptoms appearing with sufficient abruptness as to leave no doubt about the estimated time of onset. The temporal profile of ischemic stroke also includes the deficit evolution over time, which can follow 1 of several patterns: (1) rapid recovery, (2) improvement, (3) plateau, (4) stuttering (ie, waxing and waning), and (5) worsening. Each of these has diagnostic and therapeutic implications, and, when associated with specific stroke syndromes, they help guide management.

In addition to their temporal profile, the second attribute of stroke syndromes is that they indicate a focal deficit, one that can be produced by the compromise of a single vascular territory. Conversely, global neurologic symptoms are more likely the result of generalized processes. The components of stroke syndromes can be categorized in one of several clinical domains, closely following the pattern of the bedside neurologic evaluation: (1) consciousness and cognition, (2) speech and language, (3) vision and eye movements, (4) cranial nerve function, (5) motor function, (6) sensation and perception, and (7) coordination.

Transient ischemic attacks are clinically characterized by acute loss of focal brain or monocular function lasting less than 24 hours resultant from inadequate cerebral or ocular blood supply (09). The vascular territories of transient ischemic attacks may be identified according to clinical symptoms (Table 1).

Table 1. Probable Arterial Territory of Transient Ischemic Attacks According to Neurologic Symptom

To address the presentation and course of numerous stroke syndromes, we divide our discussion into the carotid and vertebrobasilar circulations while acknowledging that certain overlap may result from anomalous or variant arterial architecture. We cover both general and specific criteria for stroke localization and then merge the latter into the management continuum.

General stroke semiology

Carotid circulation. Patients with stroke syndromes in the carotid circulation present certain characteristic deficits, either in isolation or combined, to form more complex syndromes:

(1) Language abnormalities (left hemisphere). Most patients harbor neurologic control of language function within the left cerebral hemisphere (32). Therefore, stroke syndromes involving the left hemisphere usually include some type of language disorder (ie, aphasia). In these cases, language output (ie, expression) and input (ie, comprehension) are more selectively affected by lesions rostral or caudal to the rolandic sulcus respectively.

Table 2. Main Language and Speech Stroke Syndromes

(2) Perceptual disorders (right hemisphere). In most individuals, the right hemisphere is more involved in: (A) processing and interpreting sensory inputs from the outside world and (B) channeling the resulting perceptual tapestry in a way that modulates behavior and movement (ie, motor planning and execution). Patients with strokes involving the right hemisphere, particularly posteriorly, have abnormalities of multimodal sensory integration, commonly manifested as contralateral neglect.

(3) Gaze paresis. The paramedian pontine reticular formation, also known as the pontine gaze center, drives both eyes conjugately toward the same side and receives contralateral excitatory inputs from the frontal eye field and the inferior parietal lobule. Strokes affecting the cerebral hemispheres cause contralateral gaze paresis, often accompanied by forced ipsilateral eye deviation (52).

(4) Visual field defects. Lesions that affect the posterior portions of the cerebral hemispheres commonly result in homonymous field cuts. The characteristic attribute of geniculo-parieto-temporal visual field defects is that they are incongruous. Because approximately 20% of the population has a persistent fetal origin of the posterior cerebral artery, directly from the internal carotid artery via the posterior communicating artery, congruous field defects can be seen in a minority of cases.

Vertebrobasilar circulation. The structures supplied by the vertebrobasilar system represent a complex array of loci with discrete functional implications; involvement of these structures typically leads to very characteristic deficits (11). In general, the concurrent presence of any two of the following criteria is highly suggestive that the stroke involved the vertebrobasilar system:

(1) Deficits of cranial nerves II through XII. This includes two different components: (A) cranial nerve II, producing congruous visual fields defects, and (B) cranial nerves III to XII, whose nuclei and fascicles are located within the brainstem itself. The cranial nerves affected allow localization of the lesion along the distribution of the vertebrobasilar system.

(2) Deficits exclusive to the brainstem. Certain structures exist only in the brainstem and have no counterpart elsewhere in the nervous system. Due to this particularity, any injury to them leads to pathognomonic clinical findings (eg, internuclear ophthalmoplegia due to injury of the medial longitudinal fasciculus).

(3) Deficits of cerebellar function. Blood supply to the cerebellum derives from the vertebrobasilar system. Therefore, any deficit attributable to cerebellar dysfunction generally results from a derangement in the vertebrobasilar circulation.

(4) Deficits of long tracts disconnection. Many of the stroke syndromes characteristic of brainstem involvement typically affect one or another function that depends on long tract integrity (eg, hemibody strength or sensation), and, distinctly, this is contralateral to a lesion affecting ipsilateral cranial nerves (ie, “crossed” syndromes).

Other focal signs and symptoms. Some signs and symptoms can result from lesions in either the carotid or the vertebrobasilar circulations and do not allow, by themselves, specific lesion localization:

(1) Motor weakness. Present in 80% to 90% of all stroke patients, it is the most frequent clinical manifestation of stroke. Faciobrachial predominant paresis usually indicates damage to the motor cortex due to involvement of the middle cerebral artery. Pure motor hemiparesis has been associated with lesions in the internal capsule or in the basis pontis. Hemiparesis with conjugate gaze palsy may occur from lesions on the cerebral hemisphere (when eyes are deviated to the side of the lesion) or pons (when eyes are deviated contralaterally). Bilateral hemiparesis is uncommon after stroke and may represent lesions in both hemispheres, brainstem or spinal cord. Isolated monoparesis is relatively rare, representing 1% to 2% of all strokes. Upper extremity arm weakness (usually distal more than proximal) is the most common type of isolated monoparesis and is usually associated with lesions in the “hand-knob” area in the contralateral precentral gyrus. Stroke mechanism may vary; however, contralateral motor-strip infarcts have been associated with non-stenosing carotid stenosis, often with plaque ulceration or thrombus (53). This entity of “SYmptomatic Non-stenosing Carotid artery stenosis” or SYNC is being increasingly recognized with advances in carotid artery plaque imaging.

(2) Dysarthria. This pure motor abnormality of speech occurs in about one quarter of stroke cases and represents weakness of the oropharyngeal musculature from loss of suprasegmental control (33). It can result from dysfunction of the following structures: lips, tongue, jaw, and palate, which are innervated by the facial, glossopharyngeal, vagal, and hypoglossal nerves. Patients with dysarthria have inarticulate or unintelligible speech but are able to understand, read, and write.

(3) Sensory loss. This is a very common manifestation of stroke and affects over 50% of the patients. Both motor and sensory pathways are somatotopically organized; therefore, lesions result in loss of function with predictable patterns.

(4) Pseudobulbar features. “Pseudo-bulbar palsy” refers to lower cranial nerve palsy due to supranuclear lesions. There are three types of pseudo-bulbar palsy according to lesion location: the cortical form is characterized by a faciopharyngoglossomasticatory diplegia with automatic voluntary dissociation; the striatal form has the same features and also pyramidal signs, emotional lability, and intellectual impairment; and the pontine form is characterized by faciopharyngoglossomasticatory diplegia with emotional lability, pyramidal signs and sometimes cerebellar signs, without dementia. Inappropriate laughing and crying are very characteristic of pseudo-bulbar palsy. Most frequently pseudo-bulbar palsy is associated with multiple recurrent ischemic strokes although it may also have acute onset. A severe type of acute pseudo-bulbar palsy caused by bilateral opercular lesions is Foix-Chavany-Marie syndrome. Patients with this syndrome present with anarthria and bilateral central voluntary paresis of lower cranial nerves with preserved involuntary and emotional innervation (09).

Spinal cord lesions may evolve with flaccid para- or tetraplegia with complete loss below the level of the lesion and bowel and bladder dysfunction in case of transverse spinal cord infarction. The anterior spinal artery syndrome leads to the same symptoms, but sensation of touch, vibration, and proprioception is preserved (09).

Specific stroke semiology

Recognition of stroke syndromes is the cornerstone of patient care, providing a portal to the identification of important attributes about each patient. Among these, prompt diagnosis of large arterial occlusion is of paramount importance due to the patient's potential benefit from endovascular treatment (ie, thrombectomy).

Stroke syndromes. The following constitute the most important stroke syndromes, grouped by arterial systems and presented according to hierarchical position (ie, first-order vessels preceding second- and third-order branches) of the involved vessels.

(1) Anterior circulation syndromes. The large arterial occlusion syndromes associated with the internal carotid artery and middle cerebral artery can be virtually indistinguishable, depending on a variety of collateral patterns and often differing in a matter of magnitude (Table 1).

They are characterized by major cerebral hemispheric dysfunction, contralateral gaze paresis, hemianopia, and a motor deficit that affects the face and upper limb to a greater degree. Occlusion of either of the two middle cerebral artery divisions (ie, M2) results in partial forms of the full syndrome, largely motor dysfunction for the anterosuperior division, and sensory or perceptual deficits for the posteroinferior division (03). Anterior cerebral artery syndrome leads to contralateral hemiparesis, selectively affecting the lower limb and, at times, to abulia. Finally, the anterior choroidal artery syndrome includes contralateral hemiparesis (with or without ataxia), hemisensory loss, and, infrequently, incongruous hemianopia (34). With the advent of mechanical thrombectomy for acute stroke, distinguishing features of large vessel occlusion on admission has become extremely important. The Field Assessment Stroke Triage for Emergency Destination (FAST-ED) scale for pre-hospital evaluation of large vessel occlusion includes the following criteria: facial palsy, arm weakness, speech changes, eye deviation, and extinction/neglect (35).

Table 3. Carotid Stroke Syndromes from Large and Medium Artery Occlusions

Table 4. Carotid Stroke Syndromes from Smaller Occlusions and Composite Territories

(2) Vertebrobasilar syndromes. Large arterial occlusion in the vertebrobasilar system results in syndromes with catastrophic implications (Table 5). Proximal or mid-basilar artery occlusion compromises the entire brainstem and cerebellum as it also does an “isolated” vertebral artery (ie, no contralateral collateral flow) (05). Otherwise, occlusion of the vertebral artery and its most important branch (ie, posterior inferior cerebellar artery) results in Wallenberg syndrome.

The syndromes that accompany occlusion of the anterior inferior cerebellar artery and superior cerebellar artery overlap because their territories complement each other and supply common structures. Occlusion of the top of the basilar artery leads to a combination of: (A) altered sensorium, (B) visual and ocular motor abnormalities, and (C) long tract dysfunction (12; 26; 28). Unilateral posterior cerebral artery syndromes are characterized by highly congruous visual fields defects with concurrent disorders of eye movement control or behavioral abnormalities. Bilaterally, they encompass cortical blindness, with or without the patient’s awareness. Rarely, occlusion of the posterior choroidal artery is associated with hemisensory loss and homonymous sectoranopia (23; 39).

Table 5. Vertebrobasilar Stroke Syndromes from Large and Medium Artery Occlusions

The most important syndromes resulting from small arterial occlusions in the vertebrobasilar system are listed in Table 6.

These “penetrators” can be divided into 2 distinct bundles, paramedian and lateral, that supply the brainstem at all levels (08; 31; 45). The cranial nerves affected in their syndromes localize the lesion, both rostrocaudally (ie, medulla, pons, or midbrain) and transversely (ie, paramedian vs. lateral; tegmental vs. tectal).

Table 6. Vertebrobasilar Stroke Syndromes from Small Artery Occlusions

(3) Lacunar syndromes. Lacunar syndromes result from small and deep-seated infarctions, and the most important are listed in Table 7, together with their frequency of occurrence. They have been described following infarcts in numerous locations, thereby limiting their localization value (21; 36; 04).

Table 7. Lacunar Stroke Syndromes

Headache and stroke syndromes

The association of cerebrovascular diseases with headache in fairly common. Migraine related strokes are uncommon but may represent 25% of all stroke etiologies in patients below 50 years of age. Migrainous infarction is a diagnosis of exclusion and more frequently occurs in patients with migraine aura, smokers, and those using oral contraceptives (10). Cerebral arteriopathies presenting with stroke are frequently associated with headache, including reversible cerebral vasoconstriction syndrome (RCVS) and primary angiitis of the central nervous system. Although reversible cerebral vasoconstriction syndrome is frequently associated with recurrent thunderclap headaches, primary angiitis of the central nervous system is more associated with insidious and progressive headache (50). Patients with cervical artery dissection frequently have cervical pain or headache preceding stroke. Patients with carotid artery dissection may present with Horner syndrome and low cranial nerve palsy. Hemorrhagic strokes often present with headaches and in subarachnoid hemorrhage there is a typical sudden onset high intensity headache. Rupture of posterior communicating artery aneurysms can lead to ipsilateral third nerve palsy along with sudden severe headache. Table 8 summarizes headache characteristics in cerebrovascular diseases (09).

Table 8. Headache Characteristics in Cerebrovascular Disease

Atypical locations and manifestations

Infarcts of the corpus callosum splenium are rare, representing less than 1% of ischemic strokes location. Patients may present with encephalopathy, alexia without agraphia, and color anomia (51).

Usually stroke manifests with loss of function (“negative symptoms”), although positive symptoms such as hyperkinetic movement disorders may also occur. Infarcts in the putamen, subthalamic nucleus, caudate, or the posterior nucleus of the thalamus can cause movement disorders such as chorea/ballism or tremor. Limb shaking can occur, triggered by position change or exercise, and indicates decreased cerebral perfusion, most frequently caused by carotid high-grade stenosis (57).

Alien limb syndrome can be caused by a stroke in about 10% of cases. Reflexive grasping, groping, and manipulations can localize in the supplementary motor area, anterior cingulate gyrus, medial prefrontal cortex, and anterior corpus callosum of the dominant hemisphere. Alternatively, antagonistic action between the hands, extremity levitation, and uncontrolled grasping usually occur after anterior corpus callosum lesions (57).

Anton syndrome is characterized as a denial of blindness and confabulation and can occur after bilateral occipital lobe infarcts. Charles-Bonnet syndrome is characterized by visual hallucinations after loss of input into the visual cortex and can be precipitated by strokes affecting visual field. Gerstmann syndrome comprises the symptoms: agraphia, acalculia, finger agnosia, and right–left confusion and occurs due to lesions on the angular gyrus of the dominant hemisphere (57).

Bacterial and nonbacterial endocarditis often manifests with sudden confusion or somnolence, or an ‘embolic encephalopathy’, without localizing features to specific arterial territories. Imaging in such patients typically shows multiple scattered infarctions (49).

Certain etiologies can be recognized by their stroke features. For example, patients with fixed arterial stenosis (eg, intracranial middle cerebral artery stenosis, Moyamoya disease) typically develop recurrent stereotyped focal deficits. Patients with the genetic syndrome CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) accrue small-vessel strokes with psychiatric and cognitive change, leading to dementia (14). Stroke-like episodes with hearing or vision loss are seen in patients with mitochondrial disorders such as mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) (40).

Poststroke recrudescence is the phenomenon of transient reemergence or worsening of prior stroke deficits in clinical settings such as systemic infections (eg, urinary tract infection), benzodiazepine exposure or sleep cycle disruptions, and electrolyte imbalance. It is believed to result from failure of stroke recovery pathways from these systemic factors; removal of the systemic trigger results in clinical improvement to baseline. It is important to distinguish this syndrome from recurrent stroke or transient ischemic attacks, and other mimics such as seizures (54).

Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare but reversible complication occurring several years after radiation therapy. Patients manifest with headaches, seizures, or other focal neurologic deficits concerning stroke or recurrence of the underlying disease such as tumor (19).

Besides neurologic involvement, an acute stroke may lead to systemic changes, such as the stroke-heart syndrome. This syndrome is probably due to an autonomic dysregulation caused by stroke manifesting as myocardial necrosis, coronary demand ischemia, and arrhythmia. There has been an association of stroke-heart syndrome and worst short-term prognosis (46).

Cerebrovascular localization diagnosis

The diagnosis of stroke begins with the semiologic recognition of the presenting syndrome in the context of the appropriate temporal profile.

This leads, by inductive reasoning, to presumptive lesion and vessel localization, both of which are then confirmed by supportive imaging results. Next, factoring the patient’s risk profile and the natural history of the specific vascular syndrome, deductive reasoning allows the clinician to: (A) generate an etiopathogenic construct of the patient’s clinical scenario, (B) derive a set of prognostic possibilities based on the available therapeutic alternatives, and (C) choose the best course of management based on a rigorous benefit and risk assessment.

The Bamford/Oxfordshire classification categorizes stroke based on initial clinical signs (Table 9) (07). A computerized algorithm has been created to aid clinicians in this classification. The application is available and can be accessed at www.compact-stroke.com (18).

Table 9. Bamford / Oxfordshire Stroke Classification

In addition to the above stroke syndromes, an “embolic encephalopathy” (multiple cerebral infarcts causing encephalopathy without focal deficits) and “combined stroke syndromes” (multiple infarcts with a combination of the classic Oxfordshire stroke syndromes) have been described in patients with bacterial and nonbacterial thrombotic endocarditis.

Biological basis

Etiology and pathogenesis

Ischemic stroke accounts for almost 90% of all strokes, but it is hardly a homogeneous condition, having numerous potential causes (ie, etiology). There are, however, only two mechanisms (ie, pathogenesis) for the production of ischemic stroke: (A) in situ occlusion due to local vascular pathology (eg, atherothrombosis) and (B) embolic occlusion by a particle originated in an upstream source (eg, atrial fibrillation). The operational application of etiopathogenic information to bedside diagnosis requires using a robust stroke classification scheme. The most frequently used criteria is the TOAST (Table 10) (01; 02).

Table 10. Ischemic Stroke Classification Used in the TOAST

The bulk of stroke patients seen in daily practice correspond to either atherothromboembolic or cardioembolic types, as reported in the majority of the published series, and both are largely self-explanatory. Lacunar infarctions are considered small deep-seated infarcts directly resulting from in situ occlusion secondary to chronic arteriolopathy (ie, lipohyalinosis and fibrinoid necrosis).

The category of stroke of “other cause” constitutes a heterogeneous group of causative factors and underlying conditions that are capable of precipitating cerebral arterial occlusions, including: (A) thrombophilic disorders (eg, antiphospholipid antibodies), (B) inflammatory conditions (eg, vasculitides), (C) traumatic injuries (eg, dissection), (D) genetically transmitted conditions (eg, CADASIL), (E) perfusion catastrophes (eg, borderzone infarction following cardiac arrest), (F) transient dynamic arterial dysfunction (eg, reversible cerebral vasoconstriction syndrome), and (G) drug-induced arteriopathies (eg, cocaine).

The Causative Classification of Ischemic Stroke (CCS) is an automated and more detailed version of the TOAST system, with higher inter-rater reliability (Table 11). The CCS system can be accessed online (ccs.mgh.harvard.edu) and relates stroke etiology to different stroke syndromes (06).

Table 11. Ischemic Stroke Classification Used in the Causative Classification of Ischemic Stroke System

The clinical application of this information must take into account that: (A) certain large arterial occlusion syndromes commonly result from in situ occlusion (eg, internal carotid artery at its origin) whereas others frequently imply embolism (eg, middle cerebral artery); and (B) small artery syndromes may result from in situ occlusion (eg, lacunar infarction), embolism (eg, atrial fibrillation), or even large parent artery pathology (eg, basilar artery atheroma compromising pontine penetrators).

In 2014 the designation “embolic stroke of undetermined source” (ESUS) was created to identify patients with nonlacunar cryptogenic ischemic strokes with a probable embolic mechanism (30). The following criteria are used to classify a stroke as embolic stroke of undetermined source:

(1) Ischemic stroke detected by CT or MRI that is not lacunar

(2) Absence of extracranial or intracranial atherosclerosis causing ≥ 50% luminal stenosis in arteries supplying the area of ischemia

(3) No major risk cardioembolic source of embolism

(4) No other specific cause of stroke identified

Some stroke syndromes are more frequently related to specific etiologies. Border zone infarcts are more frequent in large artery atherosclerotic disease but may also occur from severe hypotension or arteriopathies such as reversible cerebral vasoconstriction syndrome, Moyamoya disease, and radiation-induced arteriopathy.

Episodes of transient monocular blindness entitled amaurosis fugax are usually related to carotid occlusion or stenosis.

Lacunar infarcts and stroke syndromes are usually related to small vessel disease and hypertensive arteriolosclerosis. These patients are often affected by cognitive impairment, due to white matter disease or strategically located lacunar infarcts. For example, the presence of lacunes in the thalamus, putamen, or pallidum have been associated with a decrease in cognitive performance (41). Lesions in the fornix has also been associated with acute amnestic syndrome presenting with anterograde amnesia often accompanied by confabulation (24). Apathy, fatigue, and delirium has also been associated with white matter disease in a metanalysis (15; 16).

Lacunar infarcts and stroke syndromes are usually related to small vessel disease and hypertensive arteriolosclerosis.

As noted above, isolated upper limb paresis has been more frequently associated with symptomatic nonstenosing carotid artery atherosclerosis (SYNC) with artery-to-artery embolism (carotid plaque rupture syndrome) (53). Failure to recognize nonstenosing carotid artery plaque rupture as a stroke mechanism may result in misclassification as embolic stroke of undetermined source instead of large artery atherosclerosis. This has management implications.

Patients presenting with vesicles in the ophthalmic root of the trigeminal nerve most and contralateral hemiparesis most probably have herpes zoster-related vasculitis.

Multiple cerebral infarcts may occur from different etiologies. In patients presenting with multiple infarcts involving the anterior circulation unilaterally the most frequent etiology is ipsilateral carotid atherosclerosis. In patients with multiple cortical infarcts in different arterial territories the most frequent etiology is cardioembolism. Frequent causes of cardiac embolism are atrial fibrillation and infectious endocarditis. A type of embolic encephalitis may occur in patients with bacterial endocarditis due to multiple infectious emboli (49). Patients with multiple deep infarcts due to microangiopathy may evolve with cognitive decline and vascular dementia.

The bow-hunter’s syndrome is characterized by ischemia in the vertebrobasilar territory after head rotation, causing dynamic vertebral artery stenosis. It is usually due to a mechanical compression from a bony structure (42). Beauty parlor stroke syndrome, also named hairdresser-related ischemic cerebrovascular events (HICE), is caused by cervical artery dissection or hemodynamic compromise related to preexisting arterial disease (17).

Patients with COVID-19 typically have thrombosis or cardioembolism to the large cerebral arteries due to hypercoagulability and endotheliopathy (48). A propensity towards large vessel occlusion, multi-territory stroke, and involvement of otherwise uncommonly affected vessels has been shown. Case reports have described atypical neurovascular presentations such as bilateral carotid artery dissection, the reversible cerebral vasoconstriction syndrome, and posterior reversible encephalopathy syndrome (PRES) (55).

Differential diagnosis

Generally speaking, the diagnosis of acute ischemic stroke should be easily made at the bedside if two categorical criteria are met: (A) the syndrome has an abrupt (ie, sudden) onset and (B) the syndrome conforms to one of those described above (ie, it is consistent with occlusion of a single vessel as its root cause). That said, published series have reported alternative diagnoses (ie, “stroke mimics”) in 30% to 50% of patients evaluated (29). The primary causes of these “mimics” include seizures (with postictal paralysis), toxic or metabolic encephalopathies, space occupying lesions, acute confusional state, migraine, inflammatory or demyelinating lesions, and hypoglycemia among others. The efficient use of ancillary studies, particularly imaging, should allow clinicians to differentiate between stroke and its “mimics.”

Transient worsening or reemergence of previous stroke-related deficits in patients with toxic and metabolic factors may be frequently misdiagnosed as a new acute stroke. The following criteria are used for diagnosis of poststroke recrudescence:

(1) Transient worsening of residual poststroke focal neurologic deficits or transient recurrence of previous stroke-related focal neurologic deficits

(2) Chronic stroke on brain imaging

(3) No acute lesion on DWI

(4) Cerebral ischemia considered unlikely (eg, symptom duration > 1 hour without new DWI lesion; no suspicion for low flow transient ischemic attack from cerebral artery stenosis or occlusion)

(5) No clinical or electroencephalographic evidence of seizure around the time of the event

The main triggers for poststroke recrudescence are infections, hypotension, hyponatremia, insomnia or stress, and benzodiazepine use (54). Neurologic deficits in poststroke recrudescence patients are usually mild to moderate and never exceed the deficits from the prior stroke.

The main differential diagnosis to transient neurologic deficits after prior stroke are described in Table 12.

Table 12. Differential Diagnosis of Transient Neurologic Deficits After Previous Stroke

Diagnostic workup

Presently, during the hyperacute phase of ischemic stroke management, CT-based techniques continue to be the most practical and informative. Nonenhanced CT allows: (A) assessment of the integrity of the neural tissue (ie, documents the presence or absence of infarction); (B) detection of alternative diagnoses (eg, intracerebral hemorrhage); and (C) qualification of stroke patients for treatment with intravenous tPA. Immediately adding CTA allows the identification of large arterial occlusion and streamlines the selection process for endovascular treatment (20; 56). CT perfusion studies provide the means to assess the ischemic penumbra, theoretically discriminating between salvageable and infarcted tissue.

In MRI, the introduction of diffusion-weighted imaging sequences and apparent diffusion coefficient maps increased the sensitivity of detecting ischemic brain tissue, even in the hyperacute stage (58; 44). In addition, gradient refocusing echo sequences can easily demonstrate even small areas of hemorrhagic transformation, of critical importance in planning the application of antithrombotic therapy, whereas MRA provides an anatomic rendition of the flow in the large arteries.

Ultrasound-based techniques, extracranial neurovascular ultrasound, and transcranial Doppler provide alternative methods for acquiring real-time information about cerebral hemodynamics and the vascular wall of the extracranial arteries. Catheter cerebral angiography is reserved for individuals whose noninvasive testing does not provide all of the diagnostic information necessary to make appropriate therapeutic decisions.

In-depth assessment of cardiogenic embolism is best accomplished using transesophageal echocardiogram due to its increase sensitivity for cardiac and aortic sources of embolization (27). Cardiac MRI is increasingly becoming an even greater asset in the diagnostic evaluation of ischemic stroke. Finally, data suggest that occult atrial fibrillation may be more prevalent than suspected, and long-term cardiac rhythm monitoring via 30-day event monitors or using implantable loop recorders is justified in many cases (47; 43).