Introduction

The approach to neurovascular disease has considerably changed over the last decade. With advances in neuroimaging, localization of the lesion has become easier. However, clinical recognition of stroke syndromes is still very important for several reasons.

First, in the acute phase, it enables diagnosis, exclusion of stroke imitators (migraine, epilepsy, PRES, anxiety, psychogenic, etc.), and recognition of rare manifestations of stroke, such as cognitive-behavioral presentations which are easily misdiagnosed.

Second, it contributes to the planning of acute interventions by localizing the stroke (anterior versus posterior circulation or cortical versus subcortical involvement) and by interpretation of imaging abnormalities. Each subtype of stroke may benefit from intravenous thrombolysis for example, but only some subtypes, such as proximal intracranial occlusion may be appropriate candidates for acute endovascular recanalization.

Third, during hospitalization, localization helps to direct the subsequent workup. If a cardioembolic etiology is suspected, for instance, it would lead to more intensive cardiac investigations, such as transesophageal echography or repeated 24-hour cardiac rhythm recording. In contrast, if a lacunar etiology is presumed, the cardiac investigation may remain limited.

Fourth, it also allows the clinician to anticipate, recognize, and treat complications related to a specific stroke type, such as large fluctuations in the lacunar “capsular warning syndrome” or brainstem compression from cerebellar edema.

Finally, making the correct diagnosis means choosing the appropriate secondary prevention. In the presence of a significant carotid stenosis, endarterectomy may be very effective if the recent stroke occurred in the territory distal to the stenosis, but of limited effectiveness if another territory is involved.

Several classifications for stroke territory, mechanism, and etiology exist. The TOAST classification [1] is most frequently used for stroke mechanism, but is partially outdated (Box 9.1). A modification of it (SS-TOAST) adds a variety of clinical and radiological criteria and seems more accurate [2]. The greater difficulty in using it has been improved by a recently published computer algorithm. The Oxfordshire method defines four subtypes of strokes according to clinical presentation attributed to a vascular territory: lacunar infarcts (LACI), total anterior circulation infarcts (TACI), partial anterior circulation infarcts (PACI), and posterior circulation infarcts (POCI).

In this chapter, we will discuss classic presentations of anterior circulation, posterior circulation, lacunar, watershed, and hemorrhagic strokes and try to identify clinical clues which can improve the diagnosis.

Anterior Circulation Syndromes

The anterior circulation refers to the part of the brain perfused by the carotid arteries. There are five main intracranial branches, which are from proximal to distal: ophthalmic, posterior communicating (PCoA), anterior choroidal (AChA), anterior cerebral (ACA), and middle cerebral (MCA) arteries. In some individuals, 2–10% according to different authors [3, 4], the posterior cerebral artery (PCA) comes from the carotid artery, via a large PCoA, while the proximal PCA originating from the basilar artery is hypo- or aplastic. In these cases, the anterior circulation irrigates the PCA territory. This variant of the circle of Willis is also known as a fetal origin of the PCA.

The anterior circulation can be subdivided into two systems: the leptomeningeal artery system vascularizing the cortex, the adjacent white matter, and the AChA; and the deep perforating artery system, perfusing the basal ganglia, the centrum semiovale, and the parts of internal capsule.

Middle Cerebral Artery (MCA)

The middle cerebral artery (MCA) is also designated as the Sylvian artery, from Jacques Dubois, known as Jacobus Sylvius (1489–1555), a linguist and anatomist in Paris. The artery is subdivided into the M1 segment, from which start the deep perforating lenticulostriate arteries, the M2 segment, corresponding to the segment after the bifurcation into superior and inferior divisions, and the M3 segment, including the insular part. The M4 segments, the leptomeningeal arteries, arise from the M3 segments and are named orbito-frontal, prefrontal, precentral, central sulcus, anterior parietal, posterior parietal, angular, and temporal arteries, with important variations in their territories.

The MCA territory is the one most frequently affected by acute strokes. MCA territory infarcts can be subtle or a devastating clinical syndrome, depending on the site of the occlusion, the extent of ischemia, the etiology, and the collateral arterial network. As collateral networks are highly variable, an occlusion of the same artery at the same place may lead to quite variable severity of the stroke and of prognosis. Large infarcts are defined as involvement of two of the three MCA territories (deep, superior, and inferior divisions) and “malignant MCA stroke” as complete or near complete MCA territory infarction with ensuing mass effect from brain edema.

Clinically, a patient with an acute complete MCA infarction presents contralateral hemiparesis, hemi-hypesthesia, hemianopsia, and ipsilateral conjugated eye and head deviation (the patient looks at his or her lesion). The patient is usually awake or presents mild drowsiness or agitation, particularly with a right infarct. Cognitive signs are always present: in the case of a left lesion, aphasia, and most of the time global, ideomotor apraxia. In the case of a right lesion, contralateral multimodal hemineglect (visual, motor, sensitive, visual, spatial, auditive), anosognosia (denial of illness), anosodiaphoria (indifference to illness), asomatognosia (lack of awareness of a part of one’s own body), and confusional state are seen. This picture suggests an M1 occlusion with or without carotid occlusion and is associated with a rather unfavorable prognosis. Particularly in younger people, malignant stroke with brain edema may develop leading to high intracranial pressure and subsequent subfacial, uncal, and transtentorial herniation. The clinical deterioration occurs typically within 48–72 hours, when vigilance decreases and initial signs worsen. New cortical symptoms may occur because of infarction of ACA or PCA arteries, which become compressed against interhemispheric falx and cerebellar tentorium, respectively. When the herniation of the medial temporal lobe continues, the uncus compresses the third cranial nerve leading to an ipsilateral fixed mydriasis and the contralateral cerebral peduncle is compressed against the cerebellar tentorium, leading to ipsilateral corticospinal signs, such as Babinski’s sign and paresis (Kernohan notch). A bilateral ptosis has also been described as an imminent sign of temporal herniation, mostly in a right malignant MCA infarct [5]. Early recognition of patients at risk enables the medical team to propose a hemicraniectomy for selected patients, a treatment which has proved highly effective if performed within 48 hours and before those signs occur [6].

A complete superficial MCA infarct, sparing the lenticulostriated arteries, suggests a thrombus in a distal part of the MCA trunk, at the bifurcation of the artery (proximal M2 segment). Motor and sensitive functions of the lower limbs are less involved than the face and arms. If leg involvement is important and persistent, concomitant ischemia in the internal capsule (AChA) or in the ACA territory should be suspected. The visual field deficit may be a contralateral homonymous hemianopia or a quadrantanopsia. The deviation of the head and the eyes is more transitory and the sensitive deficit is less severe. Cognitive deficits are similar to an M1 occlusion, but are often less pronounced or rapidly improving.

An infarct of the superior (sometimes called anterior) M2 division of the MCA manifests itself clinically with contralateral isolated brachiofacial paresis, partial brachiofacial sensitive loss (mainly tactile and discriminative modalities), transient conjugate ipsilateral eye and head deviation and aphasia (aphemia or Broca aphasia) frequently associated with buccolingual apraxia in the case of left infarcts and various degrees of multimodal hemineglect, anosonognosia, anosodiaphoria, confusion, and monotone language in right lesions. Visual fields are usually spared.

In the presence of an infarct of the inferior (sometimes called posterior) M2 division of the MCA, less frequent than superior division infarction, the presentation includes contralateral homonymous hemianopsia or upper quadrantanopsia, mild or transient brachiofacial paresis, and cognitive disturbances which are the dominant part of the picture. With a left lesion, Wernicke’s aphasia or conduction aphasia are observed and with a right lesion, hemineglect, constructional and clothing dyspraxia, spatial disorientation, behavioral changes, confusional state, hallucination, delusions, and amusia may be present.

Involvement of one of the leptomeningeal branches (M3 or M4) can produce highly circumscribed infarcts accompanied by specific neurological deficits and is most of the time related to embolism. For example, an isolated Wernicke’s aphasia occurs with occlusion of the left posterior temporal branch and suggests strongly a cardioembolic mechanism, particularly in the elderly.

The lenticulostriate arteries vascularize the basal ganglia and parts of the internal capsule. Ischemia in their territory can therefore produce severe deficits with a very small volume lesion. Cortical signs are absent or minor, except in the case of deafferentation of the cortex by interruption of subcortical–cortical pathways. Clinical signs include proportional hemiparesis, hemihypesthesia, dysarthria, hypophonia, and occasionally abnormal movements in the case of involvement of basal ganglia.

The centrum ovale receives its blood supply from medullary perforating arteries coming principally from leptomeningeal arteries. Small infarcts (less than 1.5 cm) usually present as lacunar syndromes, but deficits are often less proportional than in pontine or internal capsule lacunes.

Etiology in the deep perforator territories of the MCA is mostly lipohyalinosis and local arteriolosclerosis, in contrast with larger and multiple infarcts, which are embolic from an arterial or cardiac source. Both small and larger lesions may occur in the borderzone area between the deep (leptomeningeal) and superficial (meningeal) arteries from hemodynamic mechanisms (see below).

Anterior Cerebral Artery (ACA)

The ACA is subdivided into the A1 segment (before the anterior communicating artery [ACoA]), followed by the A2 segment (after the ACoA), then A3 segments. The A1 segment has deep perforating arteries, named the medial lenticulostriate arteries, and gives rise to the recurrent artery of Heubner (raH), which supplies the caudate head, the genu, and anterior arm of the internal capsule and the supero-anterior putamen. Both the lenticulostriate arteries and the raH are particularly vulnerable during aneurysm surgery of the ACoA.

The clinical presentation of ACA infarcts includes weakness predominantly of the distal lower limb and to a lesser degree of the upper limb, motor hemineglect, transcortical motor aphasia, and behavioral disturbances (with involvement of the supplementary motor area). Sensory hemisyndromes affecting mainly the contralateral leg are also described. Sphincter dysfunction, mutism, anterograde amnesia, grasping, and behavioral disturbances are particularly frequent in ischemia of the deep perforating arteries and the raH. Involvement of the corpus callosum can produce the callosal disconnection syndrome, secondary to interruption of the connection of physical information from the right hemisphere to the cognitive center in the left hemisphere. Therefore, it is restricted to the left hand, which presents ideomotor apraxia, agraphia, tactile anomia (inability to name objects placed into the left palm), and the alien-hand syndrome.

Anterior Choroidal Artery (AChA)

The boundaries of the territory supplied by the AChA are still controversial [7], probably reflecting interpersonal variants. The artery vascularizes to a variable degree the inferior posterior and retrolenticular part of the internal capsule, the tail of the caudate nucleus, part of the lenticular nucleus, the posterior corona radiata, the lateral geniculate body, and the beginning of the optic radiations. Clinically less important are variable contributions to the vascular supply of the uncus, amygdala, hippocampus, optic tract, parts of the midbrain (substantia nigra, cerebral peduncle), subthalamic region, and choroid plexus.

In the majority of patients, the presentation is a lacunar syndrome: pure motor or sensorimotor hemiparesis and less frequently a pure sensory deficit or an ataxic hemiparesis syndrome.

A rarer but typical presentation of AChA infarcts is the triad of contralateral severe hemiparesis, hemihypesthesia, and upper quadrantanopsia or contralateral versus ipsilateral hemianopsia (in the case of lateral geniculate body or optic tract, respectively) without cognitive disturbances, in contrast with MCA infarction. A rare but specific visual field defect is a homonymous defect in the upper and lower quadrants with sparing of a horizontal sector [8].

Rarely, cognitive signs occur in AChA infarcts secondarily to involvement of thalamocortical pathways, including hemineglect and constructional apraxia with right lesion and thalamic aphasia (fluent language with relatively preserved comprehension and repetition, but anomia, jargon speech, and semantic paraphasic errors) with left infarct. AChA infarct may therefore imitate incomplete MCA strokes.

Internal Carotid Artery (ICA)

The manifestations of acute internal carotid occlusion are quite variable, depending on the collateral status and pre-existing carotid stenosis. Embolic occlusion of the ICA, either proximally or distally, usually leads to severe stroke, showing concomitant signs of all anterior circulation arteries. Consciousness is usually more decreased and leg weakness more severe and persistent than in isolated proximal MCA occlusion.

In contrast, a progressive atherosclerotic occlusion is usually less severe with a classic subacute two-phase presentation. It may even be asymptomatic. Retinal ischemia from carotid emboli may be transient (amaurosis fugax) or persistent (central retinal artery occlusion or branch retinal artery occlusion). It often occurs in isolation and requires urgent workup, including detailed ophthalmological examination, carotid imaging, and a search for Horton’s arteritis. In the case of a chronic ICA stenosis or occlusion, a hemodynamic stress such as hypotension can lead to a watershed stroke.

In rare situations, an individual can present a limb-shaking transient ischemic attack (TIA), which manifests as a choreic or a coarse tremor-like abnormal movement of variable frequency and several minutes’ duration, mostly of the upper extremity. It typically occurs when an orthostatic stress leads to a hypoperfusion of the brain [9] secondary to carotid severe stenosis.

Posterior Circulation Syndromes

The posterior circulation is also called the vertebrobasilar circulation. The two vertebral arteries leave the subclavian arteries, pass through transverse foramina in the apophysis of the sixth to the second cervical vertebra, enter the cranium through the foramen magnum, and join together to form the basilar artery (BA). The BA gives several paramedian and circumferential branches as well as to four cerebellar arteries, and then splits into two PCAs at the level of the cerebellar tentorium. There exist numerous individual variations, the clinically most important being the fetal origin of the PCAs from the carotid arteries (via the PCoA).

Clinical Clues to Differentiate Posterior from Anterior Circulation Strokes

Important clinical symptoms and signs point to a posterior circulation stroke and should be recognized. Preceding TIAs and strokes in the days and hours before are more frequent in the posterior circulation. Similarly, headache is more frequent in the posterior circulation, is typically ipsilateral to the infarct, and may have features of primary headaches such as migraine [10].

Past diplopia, tilt of the vision, true rotatory or linear vertigo, drunken-type gait, hiccup, bilateral or crossed motor or sensory symptoms, initial decreased level of consciousness, and amnesia should be actively searched for in the history of stroke patients.

On exam, a disconjugate gaze strongly sugests a brainstem lesion. It may occur as a fixed misalignment of the ocular axis, such as in vertical skew deviation of the eyes as part of the ocular tilt reaction. Alternatively, it is due to a paresis of one or several orbital muscles as a result of an infarct of a single nucleus or its intra-axial fascicle (cranial nerves III, IV, or VI), or from connections in between these nuclei (such as in internuclear ophtalmoplegia).

Gaze paresis may also be conjugate in brainstem lesions. If the eyes are deviated towards the hemiparesis, i.e. there is “wrong-way eye deviation” if compared to a hemispheric lesion in the MCA territory, the eyes cannot be directed to the other side because the command centers allowing this action are damaged in the pons (for saccades: parapontine reticular formation, PPRF; and for pursuits: parts of the nucleus of the VI) or the midbrain (parts of the nucleus of the VI). Contrarily to most supratentorial infarcts, this eye deviation cannot be overcome with oculovestibular reflexes (“doll’s eyes maneuver”). A lateral medullary lesion (Wallenberg syndrome) leads to an ipsilateral deviation of the eyes, however, and is usually accompanied by a marked horizontal or horizonto-rotatory nystagmus.

A vertical gaze paresis (upwards, downwards, or both) points to a dorsal mesencephalic lesion and may be associated with a caudal paramedian thalamic infarct, especially if downgaze palsy is also present.

A nystagmus of central origin may be recognized by its direction (vertical, multidirectional gaze-evoked, or pendular), the absence of nausea despite clear-cut nystagmus with primary gaze, and its lack of improvement with fixation. However, it should be underlined that a medullary or cerebellar stroke can mimic a peripheral nystagmus and that vestibular ischemia from AICA may result in a peripheral vestibular lesion.

An ocular tilt reaction is characterized by the triad of skew deviation (downward displacement of the axis of the globe ipsilateral to the lesion), conjugate ocular torsion towards the side of the lesion, and head tilt to the side of the lesion. Visual tilt of the environment towards the side of the lesion is frequently associated and may result in “upside-down vision.” The ocular tilt reaction may be caused by peripheral lesion of the vestibular apparatus or the central vestibular connections including vestibular nuclei, vestibulocerebellum, and the medial longitudinal fascicle (MLF) up to the interstitial nucleus of Cajal.

Another visual sign is Horner’s syndrome, consisting of myosis, mild ptosis of the upper and lower eyelid, and hemifacial anhydrosis. It occurs with an ipsilateral dorsolateral brainstem, upper cervical, or thalamic lesion, but may also occur due to a carotid dissection, the peripheral sympathetic fibers surrounding the carotid artery.

Motor, cerebellar, and sensitive signs are less specific in brainstem lesions, but the presence of bilateral or crossed signs is suggestive. The former is due to the bilateral supply of the brainstem by one midline artery (the BA).The latter is caused by ischemia of cranial nerves and fascicles that produce ipsilateral signs and simultaneous damage to the long sensory and motor tracts that cross in the caudal parts of the brainstem. Truncular ataxia is quite characteristic of brainstem lesions, and acute unilateral deafness (with or without vertigo) suggests ischemia in the AICA territory.

Despite these clinical clues, lacunar brainstem infarcts may be indistinguishable from supratentorial ones, and proximal PCA occlusion may mimic MCA infarction. In the latter situation, hemiparesis results from ischemia to the cerebral peduncles, cognitive signs and eye deviation from thalamic involvement, and hemianopia from thalamic or hemispheric PCA ischemia. If somnolence, early anisocoria, or vertical gaze palsy are present, posterior circulation stroke is more probable than carotid territory stroke.

The Vertebral Artery (VA) and the Posterior Inferior Cerebellar Artery (PICA)

The vertebral arteries give origin to two arteries before joining to form the basilar artery: the anterior spinal artery, which supplies the medial medulla oblongata and the upper cervical cord, and the PICA, which supplies the inferior cerebellum and the dorsolateral medulla. The latter structure may also receive direct (long circumferential) branches from the vertebral artery. Three classic clinical syndromes are recognized in their territory: the medial medullary stroke (or Déjerine syndrome), the dorsolateral medullary stroke (or Wallenberg syndrome), and the hemimedullary stroke (or Babinski-Nageotte syndrome).

The medial medullary stroke is a rare stroke syndrome and classically includes contralateral hemiparesis sparing the face (corticospinal tract), contralateral lemniscal sensory loss (medial lemniscus), and ipsilateral tongue paresis (nucleus of hypoglossal nerve and tract). The laterodorsal medullary stroke is the most common of those three syndromes and is named as the Wallenberg syndrome, after Adolf Wallenberg (1862–1946), a German neurologist. Wallenberg syndrome and an infarct in the inferior cerebellum stroke can be seen in isolation or together, the latter being usually the case if the vertebral artery is occluded. Wallenberg’s syndrome includes ipsilateral thermoalgesic facial deficit (spinal trigeminal nucleus and tract), contralateral thermoalgesic deficit (spinothalamic tract), dysphagia, dysphonia due to palatal and vocal cord weakness (ambiguous nucleus), ipsilateral ataxia (inferior cerebellar peduncle), severe nausea, vomiting, nystagmus, ocular and truncular ipsipulsion (vestibular nuclei), and ipsilateral Horner’s sign (descending sympathetic tract). Hiccup is common, and may be refractory to treatment. If a Wallenberg’s syndrome is present, the presence or absence of an inferior cerebellar lesion cannot be determined clinically.

Inferior cerebellar lesions in the PICA territory without involvement of the dorsolateral medulla present with vertigo, nausea, vomiting, nystagmus, ipsilateral limb ataxia, severe gait ataxia, and ocular/truncular ipsipulsion. A deceptive appearance of PICA stroke is the isolated vertigo presentation, which can mimic a vestibular neuronitis. One clue which can help to make the correct diagnosis is the presence of an unusual nystagmus, which will be purely horizontal or direction-changing, and preservation of the vestibulo-ocular reflex with the head thrust (Halmagyi) maneuver. This maneuver should not be applied in patients with suspected vertebral artery dissection.

Isolated inferior cerebellar infarcts usually have a good outcome. However, in the case of large PICA infarcts, a post-infarct edema can provoke brainstem compression, obstruction of the fourth ventricle with subsequent hydrocephalus, and tonsillar (downward) or transtentorial (upward) herniation. In the first case, the patient develops paresthesia in the shoulder, neck stiffness up to opisthotonos, no motor responses, small and unreactive pupils, ataxic then superficial respiratory pattern, Cushing’s triad (hypertension, bradycardia, apnea), and finally cardiorespiratory arrest. With transtentorial herniation, lethargy and coma are accompanied by central hyperventilation, upward gaze paralysis, unreactive, mid-position pupils, and decerebration.

The hemimedullary syndrome is very rare and includes Wallenberg’s presentation with Déjerine’s syndrome, leading to contralateral motor and all-modalities sensory deficits, ipsilateral tongue, pharynx and vocal cord weakness and facial thermoalgesic deficit, ipsilateral ataxia, and Horner’s syndrome.

The Anterior Inferior Cerebellar Artery (AICA)

The AICA vascularizes the dorsolateral inferior pons, the antero-inferior cerebellum, the cochlea, the labyrinth, and the VIIIth cranial nerve. Major variations of the extent of cerebellar supply by the three cerebellar arteries may make localization to the AICA difficult unless certain cranial nerve deficits are present.

The classic AICA syndrome includes vertigo with vomiting and nystagmus (vestibular nuclei, vestibular nerve, or labyrinthine artery), ipsilateral deafness with tinnitus (cochlear nerve or cochlear artery), ipsilateral peripheral-type facial palsy (facial nucleus or fascicle of VII), ipsilateral facial hypesthesia (trigeminal nuclei or fascicle), ipsilateral Horner’s syndrome (descending sympathetic tract), ipsilateral ataxia, dysarthria (middle cerebellar peduncle and cerebellum), and contralateral thermoalgesic sensory deficit (spinothalamic tract). It is frequently misdiagnosed as Wallenberg syndrome, but the main clinical distinctions are the hearing loss and the peripheral-type facial palsy. Occasionally, horizontal ipsilateral gaze palsy or dysphagia are also present. More rarely, AICA territory stroke can present as an isolated vertigo or isolated cerebellar syndrome.