Strokes involve specific vessels of the cerebral circulation and result in focal neurological signs referable to the territory supplied by the affected vessels. Stroke syndromes can broadly be categorized into anterior (carotid) or posterior (vertebro-basilar) circulation phenomena (Figure 79-2). The anterior circulation includes branches of the internal carotid artery and the lenticulostriate arteries, which penetrate deep into the cerebral cortex. These vessels supply much of the cerebral cortex, the subcortical white matter, the basal ganglia, and the internal capsule. Symptoms of anterior circulation strokes depend on the hemisphere involved and the handedness of the patient. Manifestations include aphasia, apraxia, hemi-neglect, hemiparesis, sensory disturbances, and visual field defects. Specific deficits associated with the branches of the anterior circulation are listed in Table 79-1.

Figure 79-2 Circle of Willis showing arterial circulation of the brain.

Table 79-1 Anterior and Posterior Circulation Stroke Syndromes

Circulation	Vessel branch	Syndrome
Anterior	Anterior cerebral	Contralateral lower extremity paresis, mutism, apathy, pseudobulbar affect
Anterior	Middle cerebral	Contralateral hemiparesis, hemi-sensory loss, hemianopsia/quadrantanopsia, aphasia (dominant hemisphere), hemi-inattention (nondominant hemisphere)
Posterior	Posterior cerebral	Contralateral homonymous hemianopsia, alexia without agraphia (dominant hemisphere)
Posterior	Basilar	Coma, “locked in” syndrome, cranial nerve palsies, hemiparesis/quadriparesis, ataxia
Posterior	Vertebral	Lateral medullary (Wallenburg) syndrome, appendicular or truncal ataxia

Data from Kaufman DM: Clinical neurology for psychiatrists, Philadelphia, 2001, Saunders/Elsevier, p 275.

The posterior circulation consists of a pair of vertebral arteries and a single basilar artery with their branches, including the posterior cerebral arteries (PCAs). These vessels supply the brainstem, the cerebellum, the thalamus, and parts of the occipital and temporal lobes. Symptoms may localize to the brainstem (including coma, vertigo, nausea, cranial nerve palsies, or ataxia). Specific syndromes associated with the branches of the posterior circulation are also listed in Table 79-1.

EPIDEMIOLOGY/RISK FACTORS

Epidemiology

Stroke is the third most common cause of death in the United States, following only heart disease and cancer.² It is the most common disabling neurological disorder. Each year in the United States, over 700,000 new or recurrent strokes and over 160,000 deaths from stroke occur.³ Furthermore, stroke is a major cause of functional impairment: 15% to 30% of stroke survivors are considered permanently disabled.³

Risk Factors

Several major risk factors for stroke exist. Of these, age is the most important nonmodifiable risk factor; the risk of stroke more than doubles for each decade beyond age 55 years.⁴ Other nonmodifiable factors include gender (male > female), race (African Americans and Hispanics > European Americans), and genetic contributions.⁵^–¹⁰ A number of modifiable stroke risk factors have also been identified. Hypertension is one of the most important, and it is an excellent target for both primary and secondary prevention. Other risk factors include prior stroke or TIA, atrial fibrillation (AF), diabetes mellitus (DM), excessive alcohol use, tobacco use, and hypercholesterolemia.¹¹ In addition, newly identified risk factors for stroke include the metabolic syndrome and obstructive sleep apnea.¹¹

Risk-Profile Generation

Patients at risk for stroke may be stratified according to a variety of risk factors, including advanced age, hypertension, smoking status, DM, hypercholesterolemia, history of cardiovascular disease, and electrocardiographic evidence of left ventricular hypertrophy or AF. One risk-profile model, the Framingham Stroke Profile, uses the Cox proportional-hazards method to generate an individual’s 10-year, gender-specific prediction of stroke risk.¹² These and other models are important, as primary prevention efforts often focus on high-risk patients.

ISCHEMIC STROKE

Types

Several pathophysiological mechanisms lead to ischemic stroke: thrombosis, whereby a clot forms within an artery and blocks it; embolism, whereby a clot travels from a remote origin and lodges within an arterial vessel (Figure 79-3); or lipohyalinosis, whereby concentric narrowing of small penetrating arteries results in lacunar infarction. Thrombotic mechanisms cause about 20% of ischemic strokes, embolism causes about 20% of cases, and lacunar infarcts comprise an additional 25%.² The remainder is caused by more rare conditions or by an undetermined etiology (i.e., “cryptogenic stroke”).

Figure 79-3 Cardioembolism leading to acute ischemic stroke.

Given the broad array of etiologies, it is sometimes useful to categorize strokes by their anatomical basis. First, there are cerebrovascular causes of strokes. The most common is atherosclerosis of a large intracranial or extracranial artery, resulting in thrombotic stroke. Lacunar strokes are also vascular in origin, but they only affect the small branch vessels. Arterial dissection is a less common vascular cause of ischemic stroke, but it should be considered in younger patients with stroke, especially in those with a predisposing condition (such as Marfan syndrome or recent trauma to the head or neck). Use of cocaine or methamphetamine may cause stroke, likely secondary to arterial vasospasm or acute atrial dysrhythmias. Other vascular causes of stroke are rare, but include migraine, fibromuscular dysplasia, inflammation (e.g., with cerebral vasculitis), infection, and venous sinus thrombosis. Second, there are strokes related to cardiac causes, which most often result in embolic strokes. The most frequent cause of cardioembolic stroke is embolism of left atrial clot formed as a result of AF. Other, less common, causes include cardiac mural thrombus, a clot formed at the site of a prosthetic heart valve, paradoxical embolus through a patent foramen ovale, and endocarditis. Last, strokes may be caused by blood-related disorders (such as hypercoagulability, sickle cell crisis, or elevations in blood cell counts resulting from polycythemia, leukocytosis, or thrombocytosis).

Clinical Presentation

The hallmark presentation of ischemic stroke is the abrupt onset of a focal neurological deficit. Associated symptoms, such as a seizure or headache, may occur but are less common. Thrombotic and lacunar strokes are more likely to manifest with a stuttering course of waxing and waning neurological symptoms that eventually result in a complete deficit, while embolic strokes are more likely to produce a maximal deficit at the outset.

Differential Diagnosis

The classic signs and symptoms of acute ischemic stroke are usually recognizable by physicians. However, a differential diagnosis should always be created, especially in cases with atypical features, such as a nonfocal neurological examina-tion or an impaired level of consciousness. The differential diagnosis includes intracerebral or subarachnoid hemorrhage, epidural or subdural hematoma, TIA, mass lesions (such as a tumor or abscess), seizures, migraine headaches, and metabolic causes, such as hypoglycemia.

Examination

A careful history is a crucial first step in the management of a suspected acute ischemic stroke. The exact time of onset, to the minute if possible, is an essential data point, as some therapies for the management of acute stroke (such as thrombolysis) are only available within strict time frames. If the exact time of onset is not known, or if the patient was not witnessed at the time of symptom development, the time of onset by default becomes the time at which the patient was last seen to be neurologically normal. A history of similar symptoms, which may suggest a recent TIA or even a recent stroke, should also be ascertained. Essential components of the medical history include a history of cardiac problems, hypertension, DM, hypercholesterolemia, and use of tobacco or drugs. The medication list should be reviewed, especially if the patient is taking anticoagulants or antiplatelet agents. A thorough physical examination should follow, which should include the careful assessment of vital signs (including blood pressure [BP] measured in both arms). The examiner should auscultate the carotid arteries to assess for the presence of carotid bruits. Of note, a lack of a bruit may accompany a complete or an impending occlusion. Most important, a focused neurological assessment should be done with the aim of localizing the lesion supplied by the suspected vessel. Most stroke physicians use a standardized scale (such as the National Institutes of Health [NIH] Stroke Scale), which establishes a method of performing a rapid and focused evaluation and establishes standardized values for comparisons among stroke patients for treatment and research purposes.¹³

Diagnosis

Rapid diagnosis is critical to the management of acute ischemic stroke. Use of imaging, including computed tomography (CT) or magnetic resonance imaging (MRI), is essential. CT and MRI imaging help the clinician to distinguish ischemic strokes from intracerebral hemorrhages, to evaluate for other causes of symptoms, and to define the ischemic territory. CT is widely available and is highly accurate in differentiating intracerebral hemorrhage from ischemic stroke. Thus, it is the first choice of imaging in most centers. It must be performed before the administration of a thrombolytic agent in order to rule out an underlying condition (such as a hemorrhage, abscess, or tumor) that would preclude its use. MRI provides superior detection of early ischemic lesions and improved visualization of lesions of the brainstem and the cerebellum. However, in order to identify pathology within the target vessel, imaging with CT angiography (CTA) or MRI angiography (MRA) is required. Laboratory testing should always include a complete blood count (CBC), metabolic panel, serum glucose, liver function tests, and a coagulation profile. These should be obtained before sending the patient for a CT scan. If clinically indicated, such as in younger patients, other laboratory tests, such as a hypercoagulability panel or toxicology screen, should be obtained. An electrocardiogram (ECG) should always be obtained to detect arrhythmias or acute myocardial ischemia. Before any neuroimaging, the patient should be stabilized from a respiratory and hemodynamic standpoint. Consideration should be given to elective intubation if the patient’s airway may be compromised by his or her neurological deficit or by an impaired mental status.

A complete evaluation will include ultrasound of the carotid arteries, 24-hour cardiac monitoring, and echocardiography. In most cases, a transthoracic echocardiogram (TTE) study with an agitated saline bubble contrast study (to look for a patent foramen ovale [PFO]) will suffice. However, a transesophageal echocardiogram (TEE) may be indicated with specific conditions, such as in younger patients with a suspected PFO, valvular disease, or disease of the left atrium or aortic arch. Cerebral angiography is reserved for the investigation of unusual causes of stroke.

Treatment

Acute Management

In the acute setting, intravenous (IV) thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) may significantly reduce both the short- and long-term sequelae of stroke. Rt-PA exerts its action by converting plasminogen to plasmin, which helps to dissolve fibrin-containing clots. This therapy, approved in 1996 by the Food and Drug Administration (FDA) after a landmark 1995 trial by the National Institute of Neurologic Disorders and Stroke (NINDS), demonstrated a benefit to patients administered rt-PA with acute stroke less than 3 hours old.¹⁴ Overall, patients in the rt-PA group were 30% more likely to show minimal or no disability at 3 months, and the mortality rate was not significantly different between treatment and placebo arms.¹⁴ The main adverse event was a significantly higher percentage of symptomatic intracerebral hemorrhage in the treatment arm, and this remains the most important drawback of this treatment.¹⁴ Although some trials have indicated a potential benefit for patients who receive rt-PA within 3 to 6 hours, these patients have a higher percentage of symptomatic parenchymal hemorrhages, and thus treatment outside of the 3-hour window is not recommended.¹⁵ Some specialized centers may perform intraarterial (IA) thrombolysis as well. However, this is currently of limited availability, and much of the work in this area is considered investigational.¹⁶ Another FDA-approved technique for use in acute stroke is the MERCI clot retrieval device, which allows for the mechanical retrieval of an acute thrombus within 8 hours.¹⁷ In general, all forms of thrombolytic therapy should be delivered in a dedicated stroke center, where hemodynamic parameters and neurological status may be monitored carefully, and where neurosurgical backup is available in the event that the patient suffers a hemorrhagic event.

Patients who are not considered candidates for thrombolysis should receive multimodal medical management. BP in the acute setting should not be lowered aggressively. Systolic BP in the range of 150 to 160 mm Hg is often tolerated, and it may help to provide additional blood flow to ischemic, but not yet infarcted, tissue (i.e., the “ischemic penumbra”). If a patient has received IV thrombolysis, however, there is a maximum allowable BP of 185/110 mm Hg. Appropriate agents should be used emergently to lower the BP if it exceeds these values. Antiplatelet therapy has also proven beneficial both in the acute setting and for secondary prevention. Anticoagulation, with heparin or Coumadin (or both), may be indicated in conditions that require ongoing anticoagulation (such as AF), but this carries the risk of hemorrhagic conversion of the ischemic infarct. The timing of anticoagulation must take into account the size and location of the stroke, the presence of any hemorrhagic conversion (even if asymptomatic), and the overall risk/benefit profile of the individual patient.

Primary Prevention

Several primary prevention measures have demonstrated efficacy. Control of hypertension is a crucial factor in the reduction of the incidence of stroke.¹¹ A 1997 meta-analysis determined that the use of beta-blockers and diuretics were both effective in the prevention of stroke.¹⁸ Tight glucose control in DM is also recommended. Smoking cessation should be strongly encouraged. Unless contraindicated, anticoagulation for chronic conditions (such as AF with a history of thromboembolism) should be continued on a life-long basis. The role of aspirin and other antiplatelet agents in primary prevention has yet to be clarified. A randomized clinical trial of a large cohort of women demonstrated the benefits of aspirin for primary prevention in this population¹⁹; however, the benefit across low-risk populations has yet to be demonstrated.^20,²¹ Last, statin therapy has lowered the risk of stroke in patients with known ischemic heart disease,²² but its impact on patients without known cardiac disease remains under study.²³

Secondary Prevention

Antiplatelet therapy is a key component of secondary prevention. A 1994 meta-analysis demonstrated that the use of aspirin and other antiplatelet agents (such as clopidogrel) reduced the risk of recurrent nonfatal stroke by 31%.²⁰ Other effective agents include aspirin plus extended-release dipyridamole.²⁴ The use of aspirin in combination with clopidogrel is not recommended, given the lack of additional efficacy and the increased risk of bleeding.²⁵ Control of hypertension is another crucial component of secondary prevention. There may be a particular benefit associated with use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers.^26,²⁷ Unless contraindicated, stroke caused by AF should be treated with oral anticoagulation (OAC), with a target international normalized ratio between 2.0 and 3.0.²⁸ Patients should also be strongly encouraged to discontinue smoking. Lipid-lowering therapy has a proven benefit in secondary stroke prevention. A recent clinical trial demonstrated that use of statin therapy reduced the incidence of stroke and other cardiovascular events in patients with prior stroke or TIA.²⁹ In addition, weight loss and increased physical activity should be encouraged in all patients, and moderate alcohol intake allowed.²⁸ Last, carotid endarterectomy in symptomatic carotid stenosis is indicated,³⁰ and it may be considered for patients with severe but asymptomatic disease as well.³¹ Carotid stenting is another modality that has shown promise in recent years. It is currently being studied in comparison to carotid endarterectomy and in high-risk patients who are considered unsafe for surgery.³²

Prognosis

The extent of the deficit and the degree of functional impairment are important prognostic indicators. Negative prognostic factors also include advanced age and the presence of multiple medical co-morbidities. Approximately 80% of stroke patients achieve 1-month survival; however, only about 35% are alive 10 years after a stroke.³³

HEMORRHAGIC STROKE

OVERVIEW

Hemorrhagic stroke refers to the acute onset of neurological dysfunction due to a ruptured cerebral vessel. Such strokes may be classified according to the location of the hemorrhage or the presumed mechanism of injury.

Clinical Presentation

SAH most often manifests as the abrupt onset of a severe headache, classically described by the patient as the “worst headache of my life.” This severe pain is thought to be due to an elevation in intracranial pressure, leading to distortion of pain-sensitive structures. A progressive decline in mental status often follows, which may be due to decreased cerebral blood flow in the setting of elevated intracranial pressure. These symptoms are often accompanied by nausea, vomiting, and meningismus. As free-flowing blood traverses functional territories, SAH tends to produce more diffuse neurological deficits than do ischemic strokes. Ischemia or even infarction from cerebral vasospasm may occur later in the course of SAH, resulting in more focal neurological deficits.

ICH may manifest in a similar fashion, with severe headache, nausea, and vomiting. The combination of an expanding hematoma, worsening edema, and compression of brainstem structures often leads to a progressive decline in the level of consciousness. The blood pressure may be markedly elevated on presentation, and it may either be the cause of the hemorrhage or the effect of the concomitant massive catecholamine release.

Differential Diagnosis

The differential diagnosis of hemorrhagic stroke includes ischemic stroke, central nervous system (CNS) infections, subdural or epidural hematoma, rapidly expanding tumor or abscess (hemorrhage into a tumor or abscess is not uncommon), or drug intoxication. ICH may be particularly difficult to distinguish clinically from ischemic stroke, which underscores the importance of neuroimaging in this setting.

History/Examination

History gathering may be limited because of a patient’s impaired mental status. In such a case, it is important to speak with family members or other sources of collateral information. Timing, duration, onset, and types of symptoms are all important data points. SAH in particular may be preceded by the presence of multiple “harbinger” headaches in the days to weeks leading up to the event. These may be due to aneurysmal stretching before rupture or even sentinel hemorrhages. Essential aspects of the physical examination include measurement of BP, heart rate, and temperature, as well as an examination for nuchal rigidity. A neurological examination should follow, including a careful assessment of mental status.

Diagnosis

CT scanning is the preferred imaging modality for the detection of both SAH and ICH. Approximately 5% to 10% of SAHs will be undetectable by CT, due to technical limitations. In this case, if SAH is suggested by clinical history, a lumbar puncture should be performed to detect the presence of hemoglobin breakdown products (xanthochromia), which will appear less than 12 hours after the hemorrhage. Further imaging modalities include CTA or cerebral angiography, which may help to identify the aneurysm or other vascular abnormality, and Doppler ultrasound, which can monitor for the later development of cerebral vasospasm, which typically develops 5 to 14 days after the SAH. Routine laboratory testing includes a CBC, metabolic panel, and coagulation parameters. An ECG should also be performed. Typical findings that may accompany SAH include diffuse peaked T waves, a prolonged QT interval, and peaked P waves.³⁶ A neurosurgical consultation is mandatory for further management.

Treatment

For SAH due to aneurysm rupture, current management includes neurosurgical clipping or endovascular coiling of the aneurysm to prevent rebleeding. The optimal approach remains under study. The landmark 2002 International Subarachnoid Aneurysm Trial (ISAT) study, which randomized 2,143 SAH patients to clipping or to coiling (in cases in which either was deemed feasible), demonstrated improved disability-free survival in the coiling group at 1 year.³⁷ A follow-up study in 2005 of the same population demonstrated continued a survival benefit in the endovascular group for at least 7 years; however, the risk of rebleeding was slightly higher.³⁸ Potential candidates for intervention may be graded according to clinical presentation, severity of hemorrhage, and estimated surgical risk.³⁹ For SAH due to rupture of an AVM, surgical or endovascular correction may be attempted if the anatomy is favorable.

Patients with either SAH or ICH demand urgent attention for airway protection, hemodynamic management in an intensive care setting, and minimization of the sequelae of the initial hemorrhage. For SAH, interventions include bed rest with head of bed elevation to 15 to 20 degrees, careful use of mild sedating agents to control agitation, avoidance of hypotension, prophylactic prevention of vasospasm with calcium channel blockers, and seizure prophylaxis with antiepileptic medications for worse clinical grade patients. Any coagulopathy should be corrected. Hyponatremia due to cerebral salt wasting or the syndrome of inappropriate antidiuretic hormone (SIADH) is common, and should be investigated and treated accordingly. Fluid restriction is contraindicated in patients with cerebral vasospasm after SAH. Many patients (especially those with hydrocephalus or a depressed level of consciousness) with SAH will require extraventricular drainage (EVD). If cerebral vasospasm develops, medical management typically includes “triple H” therapy, consisting of induced hypertension, hemodilution, and hypervolemia. With refractory vasospasm, direct intraarterial techniques (such as direct infusion of vasodilating medications or angioplasty of severely vasospastic vessels) may be necessary.

With ICH, emergency measures (such as hyperventilation and IV mannitol) to prevent herniation and further brain injury may be required, especially for those patients who may have significant cerebral edema, brainstem compression, or severe mass effect.^40,⁴¹ Corticosteroids are not efficacious and are not indicated.⁴² The optimal approach for the management of BP is controversial. Current guidelines include the use of IV antihypertensive agents for patients with a mean arterial BP ≥ 130 mm Hg.⁴¹ Regarding neurosurgical intervention, a randomized trial of 1,033 patients with spontaneous ICH did not show overall benefit in the surgical evacuation over the conservative treatment groups.⁴³ However, a neurosurgical approach with low rates of morbidity may still be considered in selected cases. These include cases of cerebellar hemorrhage, which may be more accessible to surgical intervention, and cases of young patients with life-threatening and more superficially located hematomas.⁴¹ Future treatments may involve early hemostatic therapy with agents such as recombinant activated factor VII to reduce the volume of hematoma.⁴²

Prognosis

For SAH, survival rates depend in part on the patient’s age and neurological status, the time elapsed since the hemorrhage, co-morbidities, and other factors (such as degree of intracranial pressure). Approximately 50% of survivors have permanent brain injury from a ruptured aneurysm.³³ If the SAH is due to an AVM, survival rates are in the range of 90%.³³ For ICH, the prognosis depends on the volume of the hematoma, the site of involvement, the presence of coma, the age of the patient, and the presence of intraventricular blood.⁴⁴^–⁴⁷

NEUROPSYCHIATRIC SEQUELAE OF STROKE

Neuropsychiatric sequelae, including changes in affect, behavior, and cognition, are seen in more than half of post-stroke patients, and may be linked to lesion location (Table 79-2). Although the neuropsychiatric effects of stroke are wide-ranging and variable, symptoms tend to cluster into several categories.

Table 79-2 Neuropsychiatric Syndromes and Lesion Location

Cortical Area	Potential Neuropsychiatric Symptoms
Frontal Lobes
Orbitofrontal region	Disinhibition, personality change, irritability
Dorsolateral region	Executive dysfunction: poor planning, organizing, and sequencing
Medial region	Apathy, abulia
Left frontal lobe	Nonfluent (Broca’s) aphasia, poststroke depression (possibly)
Right frontal lobe	Motor dysprosody
Temporal Lobes
Either side	Hallucinations (olfactory, gustatory, tactile, visual, or auditory), episodic fear, or mood changes
Left temporal lobe	Short-term memory impairment (verbal, written stimuli), fluent (Wernicke’s) aphasia (left temporoparietal region)
Right temporal lobe	Short-term memory impairment (nonverbal stimuli; e.g., music), sensory dysprosody (right temporoparietal region)
Left parietal lobe	Gerstmann’s syndrome (finger agnosia, right/left disorientation, acalculia, agraphia)
Right parietal lobe	Anosognosia, constructional apraxia, prosopagnosia, hemineglect
Occipital lobes	Anton’s syndrome (cortical blindness with unawareness of visual disturbance)

Post-stroke Depression

Post-stroke depression (PSD) is one of the most common and well-studied phenomena in post-stroke patients. Up to 20% of stroke patients meet the criteria for PSD, and another 20% meet the criteria for minor depression.⁴⁸^–⁵⁰ Risk factors for the development of PSD include prior major depression, pre-stroke functional impairment, social isolation (including living alone), and possibly female gender.⁵¹ An untreated episode of PSD may last for 9 months to 1 year. The etiology of PSD is unclear and may be multifactorial (e.g., related to the degree of disability or cognitive impairment, and perhaps to lesion location as well).⁵² Depression in this population may be difficult to diagnose for many reasons, including the fact that there is often an overlap of psychiatric and somatic symptoms (such as fatigue). Confounding neurological symptoms (such as expressive aprosodias and aphasia) may hinder a complete evaluation.

PSD has a major impact on functional status, and thus it should be treated actively.⁵³ A full remission from PSD is difficult to achieve.⁵⁴ However, both selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) have proven useful in improving post-stroke mood.⁵⁵^–⁵⁷ Additionally, low doses of stimulants possess a mild antidepressant quality that may also improve mood. However, as many stroke patients have concurrent cardiac risk factors (such as elevated BP or coronary artery disease [CAD] at baseline), these agents should be used with caution (Table 79-3). For severe depression that has not been alleviated by adequate trials of antidepressants, electroconvulsive therapy (ECT) has been used successfully and safely.⁵⁸ Nonpharmacological interventions, such as cognitive-behavioral therapy, are under investigation but have not proven to be more effective than the use of medication in this population.⁵⁹

Table 79-3 Indications for Stimulant Use in Post-stroke Depression

1. Consider possible (relative) contraindications to psychostimulant use:

(a) history of ventricular arrhythmia

(b) recent myocardial infarction

(d) poorly controlled hypertension

(e) tachycardia

(f) concurrent treatment with MAOIs

2. Initiate treatment with morning dose of 5 mg of methylphenidate or dextroamphetamine (2.5 mg in frail elderly or medically tenuous patients).

3. Check vital signs and response to treatment in 2–4 hours (the period of peak effect).

4. If the initial dose is well-tolerated and effective throughout the day, continue with single daily morning dose.

5. If the initial dose is well-tolerated and effective for several hours, with a loss of effect in the afternoon, give the same dose twice per day (in the morning and the early afternoon).

6. If the initial dose is well-tolerated but is without significant clinical effect, increase dose by 5 mg per day until a clinical response is achieved, intolerable side effects arise, or 20 mg dose is ineffective (i.e., a failed trial).

7. Continue treatment throughout the hospitalization; stimulants can usually be discontinued at discharge.

Post-stroke Anxiety

Anxiety also commonly affects the post-stroke population. More than 25% of post-stroke patients meet the criteria for a generalized anxiety disorder (GAD), which commonly co-exists with major depression.^60,⁶¹ SSRIs remain first-line treatment, as they may treat symptoms of both GAD and depression. Benzodiazepines should be used with particular caution, as they may produce disinhibition or signs of toxicity, such as ataxia and oversedation.

Post-stroke Mania

Post-stroke mania occurs much less commonly than PSD. Signs and symptoms are generally similar to those of a primary manic episode and include pressured speech, grandiosity, increase in goal-directed activity, and decreased need for sleep. Symptoms may be correlated with right-sided lesions, particularly in the orbitofrontal cortex and thalamus.⁶²^–⁶⁴ Symptoms may improve with standard treatments for mania, including mood stabilizers (e.g., lithium, valproic acid, and carbamazepine) and atypical antipsychotics. However, there are few randomized clinical trials to demonstrate their benefit.⁶⁴

Post-stroke Psychosis

Post-stroke psychosis is also uncommon; it is identified in approximately 1% to 2% of all post-stroke patients.⁶⁵ Temporal lobe insults may predispose to psychosis in this population. Antipsychotics may alleviate some symptoms. However, some psychotic symptoms may arise as a consequence of complex partial seizure activity arising in the temporal lobe, and anticonvulsants, such as carbamazepine, would be the medication of choice in this setting.

Other Syndromes

In addition to the psychiatric syndromes listed previously, other syndromes are seen specifically in post-stroke patients. Catastrophic reactions may affect up to 20% of post-stroke patients.^66,⁶⁷ A mixture of anxiety, aggressive behavior, and compensatory boasting classically characterizes this syndrome. It may be related to lesions involving the anterior subcortical regions and left hemisphere.^67,⁶⁸ Risk factors include a family history of psychiatric illness. Pseudobulbar affect, also referred to as pathological emotional behavior, is a syndrome characterized by the outward emotional expression not correlating to the affect of the situation. SSRIs and TCAs may lead to some improvement in this disorder.^69,⁷⁰ Last, apathy, characterized by a notable lack of feeling or interest, is noted in approximately 20% of post-stroke patients and may co-exist with depression.^71,⁷² It may be related to lesions in the posterior limb of the internal capsule⁷² and is notoriously difficult to treat.