Carotid Artery TIAs

Platelet emboli that form on plaques at the common carotid artery bifurcation (Fig. 11-1) can lead to cerebral-hemisphere TIAs. Contralateral hemiparesis, hemisensory loss, paresthesias, or homonymous hemianopsia characterize carotid artery TIAs. Depending on whether the dominant or nondominant carotid artery gives rise to the problem, a TIA may induce neuropsychologic aberrations accompanied or unaccompanied by hemiparesis and other physical deficits. For example, dominant-hemisphere TIAs may suddenly, but briefly, cause aphasia with or without hemiparesis or homonymous hemianopsia. Similarly, nondominant-hemisphere TIAs may cause brief neglect or hemi-inattention with or without homonymous hemiparesis.

FIGURE 11-1 Top, At its bifurcation in the neck, the common carotid artery divides to form the external and internal carotid arteries. Giving off no branches until it is within the skull, the internal carotid artery immediately sends off the ophthalmic artery. The internal carotid artery then divides into the anterior and middle cerebral arteries. It also gives rise to the posterior communicating artery – not the posterior cerebral artery. Thus, each internal carotid artery perfuses the ipsilateral eye and anterior and middle portions of the ipsilateral cerebral hemisphere. The middle cerebral artery, a major branch of the internal carotid artery, supplies the deep and mid-section of the hemisphere. This region contains most of the motor cortex, sensory cortex, and, in the dominant hemisphere, the perisylvian language arc (see Fig. 8-1). Each anterior cerebral artery, another branch of the internal carotid artery, supplies the frontal lobe, including the medial surface of the motor cortex, which contains the motor innervation for the leg. The posterior cerebral artery (see Fig. 11-2), terminal branches of the basilar artery, supplies the occipital lobe, which houses the visual cortex, and most of the temporal lobe. Bottom left, An arteriogram of the carotid artery and its branches prominently displays the bifurcation (black arrow), the typical “candelabra” of branches that comprise the middle cerebral artery, and a faint anterior cerebral artery that sweeps from anterior to posterior (white arrow). Bottom right, A magnification of the bifurcation reveals an extensive circumferential plaque constricting the internal carotid artery. The remaining blood flow appears as an “apple core.” The rough interior surface of the artery gives rise to retinal and cerebral emboli.

Sometimes a TIA causes only brief visual loss in one eye, i.e., monocular blindness. Neurologists call this distinctive symptom amaurosis fugax (Greek, fleeting darkness). The underlying mechanism consists of emboli from the internal carotid artery flying into the ophthalmic artery, the carotid artery’s first branch, to induce several minutes of ischemia in the retina and optic nerve (Box 11-1). Unlike migraines, which can also cause transient visual loss, TIAs rarely cause headache or scintillations.

Between each TIA, patients have no lasting neurologic deficits. However, occasionally auscultation over the carotid artery bifurcation reveals a harsh systolic sound (bruit) that suggests carotid artery stenosis or at least atherosclerotic cerebrovascular disease. Retinal emboli (Hollenhorst plaques) of atheromatous material, which neurologists see on fundoscopy, strongly suggest carotid artery atherosclerotic plaque with stenosis.

In patients with mild cognitive impairment, TIAs may produce a brief but marked confusional state. A similar disturbance may occur after atherosclerosis slowly occludes one carotid artery, forcing the other carotid artery to supply both cerebral hemispheres through the circle of Willis (Fig. 11-2, top right). In this case, the cerebral blood supply is tenuous and emboli from the patent artery produce bilateral cerebral ischemia.

FIGURE 11-2 Top left, After ascending, encased in the cervical vertebrae, the two vertebral arteries enter the skull. They join to form the basilar artery at the base of the brain. Small, delicate branches of the basilar artery supply the brainstem and its contents. (The Roman numerals refer to cranial nerve nuclei.) Large branches, as if wrapping their arms around the brainstem, supply the cerebellum and posterior portion of the cerebrum (i.e., the occipital lobes and inferomedial portions of the temporal lobes). The posterior cerebral arteries are, for practical purposes, the terminal branches of the basilar artery. They supply the occipital cortex and the posterior, inferior aspect of the temporal lobes. Top right, Belying its name, the circle of Willis, the “great anastomoses,” is completely patent in only about 20% of people. Connections between the basilar and internal carotid arteries ideally form the circle, which should give off the anterior, middle, and posterior cerebral arteries. The circle should provide anastomoses between anterior–posterior and right–left cerebral circulations. Despite the advantages that the circle confers, junctions of the arteries are weak spots. Defects at the junctions may balloon outward to form berry aneurysms that rupture and produce subarachnoid hemorrhages. Bottom left, This axial magnetic resonance angiogram (MRA) shows the major cerebral arteries that form the circle of Willis and anterior and posterior circulations. Bottom right, This MRA highlights the major cerebral arteries and shows the anterior and posterior circulations. The anterior circulation consists of the middle cerebral arteries (MCA), anterior cerebral arteries (ACA), and the anterior communicating artery (∧), which joins the ACAs. The posterior circulation consists of the basilar (Bas.) artery and two vertebral (Vert.), posterior cerebral (PCA), and posterior communicating arteries (*), which connect the PCAs and the basilar artery.

Basilar Artery TIAs

The vertebrobasilar system, basilar artery system, or simply the posterior circulation supplies the brainstem, cerebellum, and the posterior inferior portion of the cerebrum (the occipital and medial inferior portion of the temporal lobes [see Fig. 11-2]). Emboli-generating plaques tend to develop at both the origin of the vertebral arteries (in the chest) and their junction at the base of the brain.

Symptoms and signs of basilar artery TIAs, which usually result from patchy brainstem ischemia, differ greatly from those of carotid artery TIAs (Box 11-2). Typical basilar artery TIA symptoms include tingling around the mouth (circumoral paresthesias), dysarthria, nystagmus, diplopia, ataxia, and vertigo. On rare occasions, when all blood flow through the basilar artery momentarily stops, almost the entire brainstem suffers from ischemia. The brainstem ischemia interrupts consciousness and body tone, which causes patients to collapse. This TIA, termed a drop attack, strikes suddenly and unexpectedly. (It appears similar to cataplexy [see Chapter 17].)

Vertigo represents one of the most characteristic – but perplexing – symptoms of basilar artery TIAs. As a medical symptom, vertigo means a sensation of the patient or the surroundings revolving or otherwise moving. The thoughtful physician should accept no other descriptions. In particular, the common complaint of “dizziness” has no clinical value because, depending on the patient, it may mean imbalance, lightheadedness, anxiety, confusion, or impending trouble.

The evaluation of basilar artery symptoms typically includes – as with the evaluation of carotid artery symptoms – MRI, MRA, and evaluation for cardiac and systemic illness. In addition, a transcranial Doppler examination, which harmlessly penetrates the skull, may portray the vertebrobasilar system’s architecture. Neurologists rely on the same medications used for carotid artery TIAs. Because the usual sites of vertebrobasilar stenosis remain shielded by the chest, vertebrae, and skull, an endarterectomy would not be feasible.

Transient Global Amnesia

TIAs sometimes impair the circulation of the basilar artery’s terminal branches, the posterior cerebral arteries, which supply the temporal lobes (see Fig. 11-2). Because the temporal lobes contain portions of the limbic system, particularly the hippocampi (see Fig. 16-5), posterior circulation TIAs may induce episodes of temporary amnesia and personality change – called transient global amnesia (TGA).

The fundamental feature of TGA is an acutely developing period of amnesia. During an attack, patients cannot memorize or learn new information, such as a sequence of digits, i.e., they have anterograde amnesia. They also cannot recall recently acquired information, such as the events of the last several hours or days, i.e., they have retrograde amnesia. Although patients suffer both antero- and retrograde amnesia, the anterograde amnesia is more profound, has a greater duration, causes the greater impediment, and creates more distress. As examples of their anterograde amnesia, patients typically do not know how they came to the physician’s office or the emergency room. Once there, they lose track of their responses during their examination by a physician, who may require reintroduction several times during the examination.

In the midst of TGA, individuals may perform rote but relatively complex activities, such as driving a well-known route or preparing dinner for a large family. However, unable to comprehend their situation, some individuals become distraught, agitated, or panicked. Some, as if recoiling, appear apathetic and immobile. Most, however, seem calm but bewildered.

TGAs typically occur in middle-aged and older individuals who are apt to have cerebrovascular disease. These attacks typically develop in the midst of frightening events or physical exertion, particularly sexual activity – a coincidence that might lead to misinterpretation.

In contrast to their amnesia for new facts, TGA patients characteristically retain their general knowledge and fundamental personal information. For example, they remain able to recite their name, address, telephone number, and occupation. (All this preserved memory contradicts the adjective global in TGA.)

After their abrupt onset, TGAs last for 3–24 hours, but their intensity is most pronounced during the initial 1–2 hours. By definition, the total duration must not exceed 24 hours. The recurrence rate is approximately 10% and they do not represent a risk factor for stroke. Neurologists have proposed various etiologies for TGA, including migraine, complex partial seizures, metabolic aberrations, use of certain medicines, and congestion of cerebral veins, as well as posterior-circulation TIAs. Although the posterior-circulation TIA theory remains the most popular, TGAs do not behave like TIAs. For instance, TGA rarely if ever recurs, develops in conjunction with TIAs in other arterial distributions, shows TIA-like MRI changes, or precedes a stroke.

Even in the absence of a confirmatory laboratory test for TGA, its clinical features differentiate it from other neurologic conditions. TGA patients’ preserved intellect and general knowledge, as well as their remaining fully conscious, distinguishes them from patients in delirium. TGA patients, despite their amnesia, also do not confabulate in the manner of Wernicke–Korsakoff patients. Complex partial seizures differ by producing dulling of the sensorium, simple repetitive actions, paroxysmal or other epileptiform EEG changes, and a high rate of recurrence (see Chapter 10).

Physicians using the preliminary version of the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) might be tempted to diagnose a patient with no recall of recent events as having Dissociative Amnesia, which it defines primarily as “inability to recall important autobiographical information, usually of a traumatic or stressful nature” and requires that, presumably over time, patients experience “significant distress or impairment in social, occupational, or other important areas of functioning.” However, that diagnosis would exclude TGA patients because they retain fundamental personal information. The preliminary version of DSM-5 also notes a subtype of Dissociative Amnesia, Dissociative Fugue, previously called Psychogenic Fugue, in which individuals purposefully travel or show “bewildered wandering.” Presumably, after establishing a new location, these individuals function within it and do not recall their previous life’s crucial aspects, such as a spouse, debts, or crimes. In other words, unlike TGA patients, these patients’ anterograde memory remains normal, but their retrograde amnesia persists, and the disorder lasts for months, years, or possibly indefinitely.

Risk Factors

Reflecting the necessity of preventing strokes, epidemiologic studies constantly search for stroke risk factors (Box 11-3). Although physicians customarily list stroke risk factors as individual threats, the factors actually tend to cluster. For example, obesity, elevated low-density lipoprotein cholesterol, and hypertension frequently occur together in the metabolic syndrome. Some factors, by themselves, have a weak correlation with stroke, but pose a synergistic risk when paired with others. For example, cigarette smoking correlates with stroke; however, with concomitant use of oral contraceptives or in sufferers of migraine with aura, it becomes a moderately powerful risk factor. More strikingly, smokers who are hypertensive have a 20-fold greater risk. Curiously, total serum cholesterol carries a strong risk for myocardial infarctions but a weak risk for stroke.

Age older than 65 years constitutes a powerful risk factor. Yet, about 25% of stroke victims are younger than 65 years and 12% younger than 45 years. Stroke even occurs in adolescents and young children. Hypertension, another major risk factor, similarly leads to strokes in younger individuals as well as in adults. It is also probably the most common cause of stroke-induced dementia.

Various cardiac conditions – valvular disease, prosthetic valves, acute myocardial infarction, and atrial fibrillation – comprise another risk factor because they tend to produce thromboses on valves and endocardial surfaces that embolize to the brain and elsewhere. Treatment with an anticoagulant greatly reduces the incidence of embolic stroke in patients with these cardiac diseases.

Diabetes mellitus and elevated total cholesterol represent powerful risk factors for myocardial infarction but less so for stroke. In fact, for individuals younger than 45 years, elevated total cholesterol carries little risk of stroke.

Cigarette smoking and inhaling second-hand smoke convey a significant risk factor for stroke. Even former cigarette smokers retain an almost twofold greater risk of stroke. Although judicious alcohol drinking (one drink daily to weekly) provides a slight protective effect, heavy alcohol intake poses a risk.

Migraine – in general – represents a risk factor, but one with minor significance. Any increased risk is probably restricted to migraineurs who smoke, use oral contraceptives, or have migraine with aura. Drug abuse frequently causes strokes through intravenous injection of particulate material, episodes of anoxia and hypotension, cerebral vasculitis, hypertension, and vasospasm. For example, amphetamines and cocaine are sympathomimetic stimulants that induce bursts of hypertension and prolonged arterial vasospasm that routinely lead to stroke or myocardial infarction. In particular, cocaine alkaloid (“crack cocaine”) notoriously leads to cerebral hemorrhage. By way of contrast, marijuana intoxication or even its chronic use is not associated with strokes. Studies have also implicated over-the-counter medicines, particularly phenylpropanolamine and ephedra, which are sympathomimetic ingredients of weight loss and cough suppressant medicines. Because of their association with strokes, the Food and Drug Administration has banned many of these medications.

Estrogen, when used alone as for postmenopausal hormone replacement, slightly increases the stroke risk. The danger from oral contraceptives is probably restricted to the original, high-dose estrogen preparations. Currently available low-dose estrogen preparations confer only a negligible risk for stroke.

Elevated serum concentration of homocysteine serves as a marker for an increased risk. In the autosomal recessive genetic condition, homocystinuria, children have a Marfan-like habitus, ocular lens displacement, and other anatomic abnormalities. More importantly, they routinely suffer strokes in childhood. Elevated homocysteine levels in adults are associated with the use of antiepileptic drugs and coronary artery and peripheral vascular disease, as well as stroke. Folic acid reduces elevated serum homocysteine concentrations (see Fig. 5-8), as well as reducing the incidence of fetal neural tube defects (see Chapter 13), but surprisingly, it does not reduce the incidence of strokes.

Although most risk factors relate to atherosclerosis, credible data suggest that systemic infection or vascular inflammation can also give rise to strokes. For example, elevated serum concentrations of a marker for inflammation, C-reactive protein, has a strong association with strokes. Other compelling data link periodontal disease to subsequent stroke.

The presence of anticardiolipin antibodies constitutes another example of systemic inflammation constituting a risk factor for stroke. These antibodies are a hallmark of the antiphospholipid syndrome. This syndrome is a hypercoagulable state in which mostly young women develop repeated deep vein thromboses (DVT), suffer miscarriages, and have a susceptibility to migraine and stroke. Treatment, mostly aimed at preventing thromboses, consists of anticoagulants and sometimes immunosuppressives. Although the antiphospholipid syndrome carries no specific direct psychiatric comorbidity, its associated migraines and repeated miscarriages have psychiatric repercussions. Thus, a young woman who seeks psychiatric consultation for depression following two or more miscarriages and has a history of migraine and DVT may actually have the antiphospholipid syndrome.

Examples abound of hematologic disorders causing strokes. For example, sickle cell disease and, under certain circumstances, sickle cell trait lead to strokes. Because pregnancy also induces a hypercoagulable state, it causes a small but significantly increased incidence of strokes during pregnancy, delivery, and the postpartum period. In addition, several obstetric problems, such as eclampsia, venous sinus thrombosis, cortical vein thrombosis, and ruptured aneurysms, lead to stroke-like brain damage.

Surgery is a risk factor. Not surprisingly, cardiac surgery is riskier than noncardiac surgery, urgent surgery is riskier than elective surgery, and older surgery patients are more vulnerable than younger ones.

Thrombosis and Embolus

Thromboses may simply occlude cerebral arteries and deprive the “downstream” brain of its blood flow. Similarly, emboli from the heart, aortic arch, cervical extracranial arteries, or intracranial arteries may lodge in a cerebral artery and disrupt cerebral blood flow. Because cerebral thromboses and emboli deprive a region of the brain of its oxygen supply, they cause ischemic infarction. Comprising up to 85% of all strokes, cerebral ischemic infarctions are by far the most common form.

Other important conditions that lead to stroke include vasculitis, drug abuse, sickle cell disease, and other blood dyscrasias. In short, the most frequent cause of stroke consists of an abnormality of the heart, blood vessels, or blood.

As if Napoleon’s dictum “Geography is destiny” lives, present-day neurologists readily explain that the interrupted vascular supply lines of a stroke determine neurologic deficits. The time course of a stroke suggests whether it originated in an embolus or a thrombosis. Cerebral emboli-induced infarctions develop suddenly as the embolus lodges in a cerebral vessel. Usually deficits are maximal at the onset of an embolic stroke and resolve to a certain extent over the next several days. Cerebral thromboses, in contrast, generally develop slowly or intermittently and often begin during sleep. With both embolic and thrombotic strokes, the region surrounding the infarction becomes edematous. In large strokes, edema is most severe and neurologic deficits are most pronounced during the third to fifth days. Some clinical improvement occurs as the edema resolves and ischemic areas recover; however, the infarction remains a functionless scar.

In addition to creating permanent clinical deficits, stroke scars are potentially epileptogenic. Approximately 50% of seizures that develop in adults older than 65 years originate from these lesions (see Chapter 10). Thus, patients with a history of having sustained a stroke who develop confusion, unresponsiveness, or abnormal behavior may have suffered a complex partial seizure as well as another stroke or TIA.

Necrosis

Ischemic strokes, like brain tumors, gunshot wounds, and other destructive processes, lead to cell death by necrosis. Cellular necrosis requires no cellular energy to begin or progress, but the necrotic debris (dead cells) elicits a cellular inflammatory response. In contrast, cell death by apoptosis takes place in amyotrophic lateral sclerosis (ALS), Huntington disease, and many other neurodegenerative diseases. Apoptosis also serves as the mechanism for the normal involution of several organs, including the thymus gland and ductus arteriosus. Unlike necrosis, apoptosis requires cellular energy to begin and progress, and the dead cells do not evoke an inflammatory response.

Hemorrhages

Cerebral or cerebellar hemorrhages typically occur abruptly and, because of increased intracranial pressure, produce the triad of headache, nausea, and vomiting. Patients usually lose consciousness and have profound neurologic deficits determined by the hemorrhage’s location. One special example is the cerebellar hemorrhage because it potentially leads to rapidly fatal compression of the fourth ventricle and the underlying medulla. Compression of the fourth ventricle blocks the flow of cerebrospinal fluid (CSF), which causes obstructive hydrocephalus. Pressure on the medulla depresses respiratory drive and causes coma. Physicians can diagnose cerebellar hemorrhage by its clinical manifestations – occipital headache, gait ataxia, dysarthria, and lethargy. Once imaging studies confirm a diagnosis of cerebellar hemorrhage with hydrocephalus, neurosurgeons often immediately evacuate the hemorrhage, insert a ventricular shunt, or both to relieve the pressure on the fourth ventricle and brainstem.

Hemorrhages, which are most often the result of hypertension, usually erupt in the basal ganglia, thalamus, pons, or cerebellum (see Figs 20-13 and 20-14). Trauma and use of cocaine also cause hemorrhages, but their location is not as predictable as with hypertension-induced ones. In a classic problem, patients who take a monamine oxidase inhibitor (MAOI) antidepressant and then, inadvertently or in a suicide attempt, consume certain foodstuffs, notoriously aged cheese or red wine, or receive meperidine (Demerol), develop cerebral hemorrhages. These combinations, which are sympathomimetic, lead to a burst of hypertension sufficient to cause the hemorrhage. (Notably, MAOI-A antidepressants may cause this problem, but MAOI-B medications, such as those used to treat Parkinson disease, generally do not [see Chapter 9].)

Subarachnoid hemorrhage (SAH), although usually traumatic in origin, sometimes results from a ruptured berry aneurysm. SAH most often produces a prostrating headache that patients classically describe as the “worst headache” of their life. SAH also produces nuchal rigidity and lethargy, but usually no lateralized signs. Exercising, straining at stool, and other usually benign activities can rupture an aneurysm and precipitate an SAH. A diagnostic dilemma occurs when a sudden, profound headache interrupts sex. In this case, the exertion may have led to an SAH, but more often coital cephalalgia is responsible (see Chapter 9). Thus, TGA, SAH, and a migraine variant are hazards of sexual activity.

When an aneurysm ruptures, CT and MRI usually reveal blood in the subarachnoid space at the base of the brain or within the ventricles. A lumbar puncture (LP) yields bloody or xanthochromic (yellow) CSF. Depending on the particular case, neurologists may order CT angiography, MRA, or conventional angiography to detect an aneurysm.

The traditional treatment of a ruptured aneurysm consisted of a craniotomy to clamp the neck of the aneurysm. Even for aneurysms located in accessible positions, surgical complications included vascular spasm, rupture of the aneurysm that had only been leaking, and inadvertent occlusion of the parent vessel. Current treatment options, which represent a major medical advance, include minimally invasive procedures, such as intravascular insertion of coils, epoxies, and other substances that fill the aneurysm. However, surgery remains the only option for aneurysms inaccessible by an intravascular approach.

Post-Stroke Depression

Depending on many variables – criteria, severity, time after the stroke, and whether the patient remains in a rehabilitation facility or has returned home – the prevalence of depression in stroke victims ranges from 20% to 50% within the first year and it peaks within the first 6 months of the stroke. Mood disturbances of all varieties follow stroke more frequently than they follow either a medical illness or orthopedic injury that produces similar disabilities. The majority of patients with post-stroke depression enjoy a remission within the first year after the stroke, but 20% remain depressed at 3 years.

Risk factors for post-stroke depression begin with the generally recognized risk factors for depression, such as a history of depression, close family member with depression, and ill health. Disease-specific risk factors reflect the severity of the stroke, such as dependence, functional impairments, degree and extent of paresis, curtailed activities of daily living (ADL), and cognitive impairment, including aphasia. By way of comparison, depression complicates vascular dementia more often than Alzheimer disease dementia.

If it occurs, post-stroke depression impairs patients’ recovery and lengthens their hospitalization. Depressed patients do not fully participate in their rehabilitation program or optimize their remaining cognitive function. They ultimately recover fewer ADLs. As a corollary of this, physicians might investigate stroke patients for depression if, for unclear reasons, they fail to meet expectations for recovery.

In addition to inducing morbidity, post-stroke depression portends increased mortality. Mortality rates are significantly higher at 1 and 10 years for post-stroke depression patients. Moreover, even though the physical incapacity of many stroke victims prevents their acting on suicide ideation, their suicide rate is twice that of age-matched controls. To place that figure in context, suicide occurs, compared to the general population, up to 10 times more frequently in Huntington disease patients, 7 times in multiple sclerosis patients, and 4 times in epilepsy patients. Risk factors for suicide in stroke patients include prior stroke, impaired ADLs, and depressive symptoms.

In some, but not all, studies, remission of post-stroke depression has correlated with improved rates of recovery of ADLs and other physical measures. Remission also has correlated with improved cognitive function.

Before leaping to the diagnosis of post-stroke depression, physicians should keep in mind that some stroke symptoms mimic depression. Failing to appreciate them may lead to misdiagnosis and unwarranted prescriptions. For example, patients with a nondominant-hemisphere stroke may deny having a hemiparesis, not because of depression, but because of anosognosia. Also, their conversations may lose their emotional tone because of aprosody (see Chapter 8). In another situation, strokes – individually or in succession – that damage both frontal lobes frequently result in apathy, pseudobulbar palsy with unprovoked crying and emotional incontinence (see Chapter 4), or a paucity of verbal output because of abulia (see Chapter 7). Finally, following several strokes, patients often develop sleep disturbances and vegetative symptoms.

To compound the diagnostic difficulty, medical care itself may produce complications that mimic depression. For example, some medications – beta-blockers and antiepileptic drugs – routinely administered to stroke patients may induce or exacerbate depressive symptoms and cognitive impairment. Also, sleep deprivation, uncomfortable or painful procedures, and psychologic factors, such as disorientation, fear, and isolation, may express themselves as withdrawal and expressions of hopelessness.

Finally, physicians should further pause before concluding that depressive symptoms result from either a neurologic or psychiatric process. Such “either/or” diagnostic reasoning is fraught with potential for error. Whatever a stroke’s sequelae, patients may have subtle post-stroke depression comorbid with neuropsychologic deficits. In fact, the two factors may act synergistically.

In another consideration, several studies have challenged the classic notion that strokes in the left frontal lobe most often cause post-stroke depression. These studies have reported equally strong correlations between depression and lesions in the right as well as the left cerebral hemisphere, and occasionally depression secondary to ones in the basal ganglia, thalamus, and other subcortical structures. In addition, some studies correlated the stroke’s location with depression only during the immediate post-stroke period.

Several trials of treatment of post-stroke depression have reported success with tricyclic antidepressants, selective serotonin reuptake inhibitors, and, in the elderly, psychostimulants. However, most trials found that antidepressants did not prevent depression or improve functional outcome. Moreover, no consensus emerged as to the best antidepressant, much less showed that any had a major impact. Psychological treatments in several studies improved patients’ mood, but they did not help other parameters. Although electroconvulsive therapy may cause more confusion than usual in stroke patients, it is overall safe and effective compared to other treatments.

Other Psychiatric Complications

Following a stroke, approximately 10–25% of patients, particularly women and younger patients, have anxiety. When it occurs, post-stroke anxiety typically leads to unpleasant physical manifestations, including insomnia and decreased energy. It also impairs function and rehabilitation. In the majority of these patients, depression is comorbid. As with post-stroke depression, post-stroke anxiety has no consistent anatomic correlation. No specific therapy is available for pure post-stroke anxiety, but when it is comorbid with depression, antidepressants may help.

In contrast to the frequent occurrence of post-stroke depression, mania following a stroke rarely occurs. Moreover, studies have not determined its characteristics, underlying pathology, or treatment.

Delusions, hallucinations, and other symptoms of psychosis also rarely develop after a stroke. When these symptoms occur, they typically reflect pre-existing dementia. Unlike other post-stroke psychiatric problems, post-stroke psychosis is associated with seizures.

Locked-In Syndrome

Among their innumerable patients who have sustained strokes, TBI, or other structural lesions and appear completely incapacitated, neurologists search for the patient with the locked-in syndrome. This rare but important condition describes patients who remain mute, quadriplegic, bedridden, and totally dependent on caregivers; however, they actually are alert, have intact decisional capacity, and can communicate by moving their eyes. In other words, their completely disabled body encases (“locks in”) an intact mind.

The locked-in syndrome usually results from a stroke that damages the base (ventral portion) of the pons (basis pontis, see Fig. 2-9) and medulla (bulb). The exact cause is usually a thrombosis or embolus that occludes a branch of the basilar artery (see Fig. 11-2). The stroke causes bulbar palsy and bilateral interruption of the corticospinal tracts. It renders patients mute, quadriplegic, apneic, and dysphagic. Patients almost always require tracheostomy, ventilator support, and feeding tubes. Although locked-in patients have lost almost all their motor ability, their higher functions, like language comprehension and cognitive ability, remain intact.

The locked-in syndrome may not only result from brainstem strokes. Several peripheral nervous system (PNS) diseases, such as myasthenia gravis, ALS, and Guillain–Barré syndrome (see Chapters 5 and 6), may cause extensive enough paresis of cranial and limb muscles to cause it and require mechanical supports.

Despite the devastating damage in the locked-in syndrome, the upper brainstem, reticular activating system, and cerebral cortex remain intact. Moreover, the physiologic circuits between the cerebral cortex and upper brainstem, including the thalamus, continue to reverberate (Fig. 11-3). Thus, locked-in patients retain cognition, affective capacity, and, given sufficient clues, a sleep–wake cycle. Patients who are otherwise completely paralyzed can still purposefully move their eyes and eyelids. By closing their eyelids in a “yes” or “no” pattern, they can communicate by answering questions. The preserved circuits between the thalamus and cerebral cortex generate a relatively normal EEG.

FIGURE 11-3 The locked-in syndrome usually results from an infarction of the ventral or basilar portion of the lower brainstem, typically at the basis pontis (see Fig. 2-9). A lesion in this area (indicated by the bar) would sever the corticospinal tracts and directly injure cranial nerves IX through XII. However, it would not damage several vital systems: (1) the reticular activating system of the brainstem; (2) the cerebral hemispheres, particularly the cerebral cortex; and (3) the cerebral and brainstem system that governs ocular movement (see Fig. 12-12). This lesion, which is nowhere near the cortex, would not affect the brain’s cognitive, language, or visual centers. The EEG is relatively normal because the lesion also spares the circuits reverberating between the thalamus and the cerebral cortex (indicated by the loop), which generate the organized, relatively regular background EEG activity.

Physicians should base management of locked-in syndrome patients on its inherent preserved cognizance and decisional capacity. These patients comprehend people talking and reading to them. They can convey their wishes, including decisions regarding their medical care. In fact, locked-in syndrome patients may direct the removal of their own artificial life-sustaining equipment. Patients in a locked-in syndrome from a brainstem stroke may partially recover, but their overall prognosis is poor. In contrast, patients debilitated from a PNS illness often fully recover.

Physicians might examine stroke victims (and those with severe, extensive PNS disease) for the locked-in syndrome if they are unable to speak or move their limbs, but have their eyelids open and voluntarily look from side to side. The physician should ask these patients to blink a certain number of times. If they correctly respond, the patient, physician, and family can establish a system of communication. If patients can blink meaningfully, the physician should test their ability to see and calculate. Afterward, physicians can undertake detailed mental status testing.

One Navy veteran, who was in a stroke-induced locked-in syndrome, communicated using eyelid blinks in Morse code. In another example, a motor vehicle accident left an editor of a Paris fashion magazine, Jean-Dominique Bauby, in the locked-in syndrome. By blinking to an assistant, he dictated a short autobiography that was made into the film with the same title, The Diving Bell and the Butterfly. Currently, an EEG–computer interface shows promise.

Persistent Vegetative State

Extensive cerebral cortex damage – without brainstem damage – may cause PVS. Like locked-in patients, PVS patients remain bedridden with quadriparesis and incontinence, but with their eyelids open and eyes moving about. However, in stark contrast, because of the cortex damage, PVS patients lack awareness of themselves and their surroundings, have no cognitive function, and cannot communicate in any manner. With their lack of consciousness, patients in PVS can neither perceive pain nor suffer. Neurologists sometimes describe this state as “wakefulness without awareness” (Figs 11-4 and 11-5). Nevertheless, the undamaged brainstem continues to regulate the body’s vegetative functions, e.g., metabolism, breathing, temperature regulation, and digestion. Also, unlike comatose patients, PVS patients continue their sleep–wake cycle.

FIGURE 11-4 The persistent vegetative state, which can be caused by cerebral anoxia or numerous other conditions, results from extensive damage to the cerebral cortex or the tissue immediately underlying it (indicated by the bar). These injuries impair all cerebral functions, including cognitive ability, purposeful motor activity, vision, and speech.

FIGURE 11-5 Patients in the persistent vegetative state tend to assume a decorticate (flexed or fetal) posture because of extensive cerebral damage. Appearing to be awake, they remain mute, unable to respond to visitors or examiners, and, except for breathing and roving eye movements, motionless. Patients almost always require combinations of nasogastric tubes, intravenous lines, urinary catheters, and tracheostomies. Being immobile and requiring mechanical devices, they are vulnerable to aspiration pneumonia, urinary tract infections, and decubitus ulcers.

Damage of the cortex and cortical–brainstem connections in PVS renders the EEG abnormal. The damage also causes positron emission tomography (PET) and functional MRI (fMRI) to show generalized, markedly reduced cerebral glucose metabolism and blood flow.

In what might constitute a misleading appearance of consciousness, PVS patients lie in bed with open eyelids, retain sleep–wake periods, and move their limbs as a reflex or in response to noxious stimulation. In addition, their eyes, moving spontaneously and randomly, may momentarily fix on a face or reflexively turn toward voices or other sounds. However, PVS patients perform none of these actions consciously or deliberately. Unfortunately, relatives may misinterpret patients’ appearance, eye movements, and other activities as appreciating their presence or understanding their words. Relatives often not only overestimate the patient’s cognition, they may treat the patients as if they were suffering, in a state of suspended animation, or only temporary unconsciousness.

Extensive cerebral insults, including TBI, anoxia, profound hypoglycemia, and multiple or massive strokes, or progression of neurodegenerative illnesses, particularly Alzheimer disease and childhood-onset metabolic disorders, often lead to PVS. After existing for 1 month in a vegetative state, patients fall into the category of persistent vegetative state. After an acute insult, some patients remain comatose for weeks before entering a vegetative state and, from there, the persistent state. Patients with neurodegenerative illnesses usually slip into the PVS without first entering coma. Once patients have been in TBI-induced PVS for 1 year or from neurodegenerative illness for 3 months, they have no realistic chance of recovery.

Beyond its heart-wrenching aspects, PVS raises important ethical and legal considerations. Acting on patients’ living wills or other directions that they “not live like a vegetable,” some relatives have sought to discontinue nutrition and artificial supports. On the other hand, other relatives have sought to maintain artificial supports despite its futility. Several well-known legal cases have explored the limits of maintaining PVS patients in accordance with their own or their proxy’s wishes or in the absence of any known wish. With no known wish, courts generally have allowed the health care proxy to make decisions, including removing food and nutrition.

Minimally Conscious State

In the minimally conscious state, strokes or other cerebral insults have impaired patients’ level of conscious awareness of themselves and their environment, but not to the degree seen in either coma or a vegetative state. Patients in this twilight zone must display discernible behavioral evidence of consciousness. Their behavior must appear on a reproducible and sustained basis, but not merely constitute a reflex. As examples, patients must follow one or more simple commands; gesture or say “yes” and “no” (regardless of accuracy); speak intelligibly; appropriately, not reflexively, smile or cry; respond to questions by speech or gesture; or use their hands to reach or manipulate objects. These patients may consciously perceive pain. Although the etiologies are similar, patients in the minimally conscious state generally have a more favorable outcome than those in PVS.

In contrast to the EEG and PET in PVS, which fail to show meaningful cerebral cortical activity, these studies in the minimally conscious state may show some organized cerebral cortical activity. Widespread reports in the general press that treatment with zolpidem (Ambien), which modulates GABA receptors, aroused patients in PVS or minimally conscious state remain unconfirmed in the neurologic literature.

Laboratory Tests

In most cases, CT or MRI confirms a diagnosis of stroke or reveals common alternatives, such as brain tumor, abscess, or subdural hematoma (see Chapter 20). CT indicates the presence and location of most strokes, except those that are very acute, small, or located in the brainstem or other regions of the brain located in the posterior fossa (where bone artifacts may obscure them). Compared to CT, MRI provides better resolution of small strokes, visualizes ones in areas of the brain surrounded by bone, and, by using special software subprograms, shows acute infarctions. MRA can visualize extra- and intracranial cerebral arteries and most regions of stenosis and occlusion (see Chapter 20). As diagnostic tests in this situation, skull X-rays and EEGs are superfluous.

Examination of the CSF through an LP may reveal signs of an SAH or infection, such as meningitis and encephalitis, that mimic a stroke. However, LP is unnecessary for a routine stroke and physicians should avoid performing the procedure in the presence of an intracranial mass lesion (see transtentorial herniation, Chapter 19).

Therapy

For acute ischemic strokes, neurologists may administer thrombolytic agents, such as tissue plasminogen activator (tPA), that ideally will dissolve cerebral arterial occlusions and restore cerebral blood flow. As could be anticipated, tPA carries the potential for cerebral hemorrhage and other complications. Because of its dangers, neurologists must administer tPA according to a demanding set of guidelines, including giving it within 3 hours in most patients and 4.5 hours in selected patients after the onset of a stroke, and withholding it if the patient has undergone major surgery within the previous 14 days, the blood pressure exceeds 185/110 mmHg, bleeding parameters fall outside a narrow range, or a CT shows signs of intracranial hemorrhage. Administering thrombolytic agents by angiography directly to an occlusion and neuroprotective agents (medications that preserve ischemic brain tissue) remains in development. Steroids, oxygen, and vasoactive medicines have no proven benefit.

Medical and nursing care aims to prevent stroke complications, such as aspiration pneumonia, decubitus ulcers, DVTs, and urinary tract infections. It also aims to prepare stroke patients for rehabilitation. If the patient is not alert or has a depressed gag reflex, neurologists administer medications and nutrition intravenously or through a nasogastric tube. To prevent decubiti, which are unsightly, malodorous, and liable to lead to sepsis, neurologists usually order air mattresses, sweat-absorbent bed surfaces (e.g., artificial sheepskins), and elbow and heel cushions for paretic limbs. Because urinary incontinence adds to the likelihood of developing decubitus ulcers, leaves patients cold and wet, and creates repugnant odors, neurologists generally order catheters or diapers.

The medical staff should place the patient’s bed against the wall so that visitors and staff approach the patient from the side without perceptual impairment. For example, the staff should place the bed of a patient with a left hemiparesis and a left homonymous hemianopsia with the wall to the patient’s left. In that situation, with visitors approaching only from the right side, patients will see them in their right visual field, and patients’ right hand can grasp important objects from the bedside table (e.g., call buttons, television controls, and telephone).

In the initial phase, relatives of stroke patients can be helpful by orienting the patient and bringing a luminous dial clock, a calendar, and pictures; repositioning the patient; moving paretic limbs to avoid contractures; and locating appropriate rehabilitation facilities. Eventually many relatives have difficulty in coping with the patients’ disabilities and develop caregiver stress. They have depression at about three times the usual rate.

Physical therapy will often maintain the patient’s muscle tone, forestall decubitus ulcers, and prevent contractures. It will usually help patients with simple hemiparesis to regain the ability to walk, circumvent some impediments, and avoid maladaptive but expeditious physical compensations. Moreover, physical therapy necessarily entails the “laying-on of hands,” which conveys emotional as well as physical support.

Speech therapy may help with dysarthria and offer patients encouragement; however, it probably does not restore language function in aphasia. “Cognitive and perceptual skill training” for impaired mentation, sensory impairment, and visual loss remains without proven value.

Hemi-inattention and anosognosia usually resolve spontaneously within the first month. However, aphasia usually improves to almost its fullest extent by 4–6 weeks. Deficits persisting after that time usually do not resolve. Poor prognostic factors for recovery – as any physician might sense – are advanced age, dementia, incontinence, bilateral brain damage, and prior strokes. If asked for a consultation, psychiatrists might particularly search for depressive symptoms with or without anxiety, maladaptation, denial, and other defense mechanisms.