Clinical Vignette

A 68-year-old white man with a history of hypercholesterolemia and 50-pack-year smoking presented with transient episodes affecting the right side of his body. During the first episode, he had weakness of his right leg, lasting for about 10 minutes. The second spell happened 1 week later and was characterized by speech difficulties, right facial drop, and right arm weakness that lasted for 2 hours. The patient came to the emergency department (ED) 3 days later. Brain magnetic resonance imaging (MRI) with diffusion-weighted imaging demonstrated two small strokes in the left frontal lobe, one in the ACA territory and the second one in the MCA distribution. Magnetic resonance angiography (MRA) of the head and neck was remarkable for a 70–80% stenosis of the left ICA, confirmed by carotid ultrasound. The patient was started on antiplatelet treatment and a statin. Smoking cessation education was provided. A right carotid artery endarterectomy was successful, with no subsequent TIAs.

Clinical Vignette

A 70-year-old white man with arterial hypertension and high cholesterol presented with 1 month of recurrent 1- to 2-minute episodes of left extremities shaking that occurred only on standing. His blood pressure (BP) was 110/80 mm Hg, and neurologic examination showed a left pronator drift, but was otherwise normal.

Head computed tomography (CT) showed small strokes in the arterial border zone between the right MCA and ACA and right MCA and PCA distributions. Head and neck computed tomography angiography (CTA) demonstrated a right ICA occlusion. CT perfusion showed hypoperfusion in the right MCA territory, worse in the border zone areas. Collateral flow through the right ophthalmic, anterior communicating, and posterior communicating arteries was detected by transcranial Doppler and conventional angiogram. Patient was started on antiplatelet treatment as well as a statin drug and his antihypertensive medication dose was decreased, with a subsequent increase in the systolic BP to 140–150 mm Hg. No further episodes occurred.

The above vignettes illustrate the two mechanisms of stroke or TIA in large artery atherosclerotic disease, intra-arterial embolism (the first vignette) and hypoperfusion (the second vignette). Identification of the exact mechanism has important therapeutic implications.

TIAs are common in patients with carotid artery disease and usually precede stroke onset by a few days or months. TIAs caused by intra-arterial embolism from a carotid source may not be stereotypical. TIA symptoms vary, depending on which ICA branch is involved. For example, patients can have a first episode of a transient right leg weakness and weeks later have another spell characterized by expressive aphasia, right facial droop and weakness of the right hand. This depends on the destination of the emboli. In the first example, the ACA territory is the destination and in the later example, the MCA territory. In contrast, hemodynamic “limb-shaking” TIAs as in the second vignette presented above are often stereotypical and posturally related and are usually seen in patients with high-grade ICA stenosis or occlusion. In this classic example of a hemodynamic ischemia, patients present with recurrent, irregular, and involuntary movements of the contralateral arm, leg, or both, usually triggered by postural changes and lasting a few minutes. These spells likely represent intermittent loss of cortical control and paralysis and differ from a focal seizure in which the movements are more regular and rhythmic and usually correlate with focal repetitive cortical hyperactivity seen on electroencephalogram.

Another important clue to ICA disease is episodes of transient monocular blindness (TMB). TMB refers to the occurrence of temporary unilateral visual loss or obscuration that is classically described by careful observers as a horizontal or vertical “shade being drawn over one eye,” but most frequently as a “fog” or “blurring” in the eye, lasting 1–5 minutes. It often occurs spontaneously but at times is triggered by position changes. Positive phenomena such as sparkles, lights, or colors evolving over minutes are more typical of migrainous phenomena and help to differentiate such benign visual changes from the more serious TMB, a frequent harbinger of cerebral infarct within the carotid artery vasculature. Rarely, with critical ipsilateral internal carotid stenosis, gradual dimming or loss of vision when exposed to bright light, such as glare of snow on a sunlit background, can be reported and is due to limited vascular flow in the face of increased retinal metabolic demand. Besides carotid atherosclerosis, other etiologies of TMB include cardiac embolism and intrinsic ophthalmic artery disease due to processes such as atherosclerosis or arteritis (see Giant cell or Temporal arteritis in Chapter 11), as well as decreased retinal perfusion from glaucoma or increased intraocular pressure. It is not uncommon that homonymous field deficits are reported by patients as monocular visual loss off to the affected side, and careful questioning as to whether each eye was checked independently and whether the visual difficulty involved the perception of a quadrant or one half of the visual world is essential. For example, patients with left occipital infarctions or transient ischemia may report right-sided vision loss, but further questioning reveals that they were unable to read the right side of street signs or a license plate and while covering the “unaffected” left eye the seemingly abnormal right eye had retained vision within the distribution of the unaffected left homonymous field (Fig. 55-7).

Figure 55-7 Ocular Signs of Large Vessel Disease.

As in the first vignette, strokes from intra-arterial embolism from ICA disease are usually cortically based. Symptoms depend on whether branches of the MCA, ACA, or both are involved. The PCA territory may rarely be affected by intra-arterial emboli from ipsilateral ICA stenosis or occlusion in patients with anomalous normal vascular variants as in a persistent fetal PCA.

Neurologic findings vary by the location of the occlusion and presence of collateral circulation (Fig. 55-8). A large MCA stroke is usually seen in patients with MCA main stem occlusion without good collateral flow, whereas deep or parasylvian strokes are the most common presentation when enough collateral flow is present over the convexities.

Figure 55-8 Occlusion of Middle and Anterior Cerebral Arteries.

Contralateral motor weakness involving the foot more than the thigh and shoulder, with relative sparing of the hand and face is the typical presentation of distal ACA branch occlusion. Conversely, prominent cognitive and behavioral changes associated with contralateral hemiparesis predominate in patients with proximal ACA occlusions and the involvement of the recurrent artery of Huebner (caudate and interior limb of internal capsule infarct).

Hemodynamic strokes usually involve the border zone territory between ACA and MCA (anterior border zone), MCA and PCA (posterior border zone), or between deep and superficial perforators (subcortical border zone) and cause typical clinical symptoms outlined in Table 55-1.

Table 55-1 Clinical Symptoms in Patients with Border Zone Strokes

Clinical Vignette

A 70-year-old woman with history of diabetes mellitus and hypercholesterolemia presented to the ED reporting mild right-sided weakness first noticed on awakening 2 days previously. The hemiparesis progressed to a right hemiplegia with dysarthria within 48 hours without change in the patient’s level of consciousness. Head CT demonstrated a stroke involving the left centrum semiovale. Head CTA showed a distal M1 segment stenosis. Patient was started on an antiplatelet treatment and a statin. Pharmacologic treatment for her diabetes was maximized. Once stable, patient was transferred to a rehabilitation facility with partial recovery of her motor deficits.

This vignette describes a classic course of subcortical infarct from poor perfusion of the lenticulostriate vessels secondary to a fixed lesion in the ipsilateral MCA. The patient’s symptoms evolved from relatively mild hemiparesis to complete paralysis within 2 days. Unlike large MCA infarctions, there was no impairment of the patient’s level of consciousness despite the progressive nature of the neurologic deficit. In contrast, large cortical MCA lesions may also evolve over 2–4 days but due to development of cerebral edema and increased intracranial pressure, altered level of consciousness and even coma are commonly seen.

Intrinsic occlusive disease of the MCA and ACA are more common in Asians, Hispanics, and African Americans than in Caucasians and are more common in women than in men. Arterial hypertension, diabetes, and smoking are the most common risk factors, with a lower incidence of high cholesterol, coronary artery disease, and peripheral vascular disease. Although TIAs can occur, they are not as common as in patients with ICA disease and usually occur over a shorter period of hours or days. When strokes occur, initial symptoms are typically noticed on awakening and often fluctuate during the day, supporting a hemodynamic mechanism.

Clinical Vignette

A 76-year-old white man with a history of hypercholesterolemia and a previous myocardial infarction had acute onset of vertigo associated with vomiting and gait difficulties 2 days before presentation. On admission, he had sudden onset of slurred speech and lack of right arm coordination. Head CT demonstrated an old right posterior–inferior cerebellar artery (PICA) stroke and a subacute left PICA stroke. Head MRI with diffusion-weighted imaging showed a new right superior cerebellar artery stroke. Head and neck CTA showed occlusion of the left vertebral artery (VA) origin, a hypoplastic right vertebral artery, and an embolus in the middistal portion of the basilar artery. He was started on a statin and on anticoagulation. Clinically, the patient improved significantly.

The vertebral arteries originate from the subclavian arteries in the neck. Stenosis or occlusion of the proximal subclavian arteries and the vertebral arteries at their origin rarely causes symptoms because of the concomitant development of adequate collateral circulation within the neck through the thyrocervical and costocervical trunks and other subclavian artery branches eventually flowing into the distal vertebral artery (see Fig. 55-3). More often, patients with subclavian and concomitant vertebral-origin stenosis have symptoms related only to upper extremity ischemia. They report pain, coolness, and weakness of the ipsilateral arm. Rarely does chronic atherosclerotic disease at the vertebral origins, even when bilateral, cause significant vertebrobasilar system flow reduction to cause symptoms. When stenosis or occlusion of the VA origin leads to TIAs or stroke, intra-arterial embolism is the commonly recognized mechanism. The embolus usually lodges in the distal vertebral artery, causing a PICA stroke, or passes through, leading to a “top of the basilar syndrome” (Table 55-2).

Table 55-2 Clinical Manifestations of Ischemia in the Vertebrobasilar System According to the Artery Involved*

* AICA, anterior inferior cerebellar artery; PCA, posterior cerebral artery; PICA, posterior–inferior cerebellar artery; SCA, superior cerebellar artery

Distal intracranial VA atherosclerotic disease most often occurs at the level of the penetrators to the lateral medulla and at the take-off to the PICA. Occlusion at this site presents as a Wallenberg syndrome (lateral medullary syndrome) or cerebellar PICA stroke or both. Lateral medullary syndrome progressing into coma and herniation due to an associated large PICA cerebellar infarction is not uncommon and emphasizes the need to investigate and closely observe those with Wallenberg syndromes for unfolding signs of wider neurologic involvement.

Atherosclerosis of the basilar artery most often affects its proximal and mid portions. Patients experience TIAs characterized by transient diplopia, dizziness, incoordination, and weakness affecting both sides at once or alternating between sides over minutes and even hours or days (Fig. 55-9). As in other occlusive large artery disease, some patients with severe basilar stenosis develop prominent headaches in the weeks before focal symptoms commence. The headache is thought to be from developing posterior circulation collateral flow. When stroke occurs, the most commonly affected area is the basis pons, with bilateral, often asymmetric, hemiparesis, pseudobulbar syndrome, abnormalities of eye movements (sixth nerve palsy, unilateral or bilateral internuclear ophthalmoplegia, ipsilateral conjugate gaze palsy, “one and one-half syndrome”), nystagmus, and if the reticular activating system is involved, coma (Fig. 55-10). Presence of coma or altered level of consciousness is dependent on collateral flow to the tegmentum from other vessels. If the pontine and midbrain tegmentum is spared, bilateral motor and sensory signs as well as varying degrees of ophthalmoplegia may be present without altered consciousness, such as in the “locked in” syndrome.