Three general concerns dictate the management of atrial fibrillation:

• Controlling the heart rate
• Controlling symptoms
• Preventing thromboembolic events, including stroke.

When seeing a patient with newly diagnosed atrial fibrillation, these same three concerns should be kept in mind, but several additional issues must be addressed:

• Reversible causes of atrial fibrillation must be ruled out
• The true time of onset of the atrial fibrillation and the frequency of the episodes should be ascertained, if possible
• A careful estimation of the patient’s symptom burden should be made.

Atrial fibrillation is common and has a huge impact in terms of the morbidity, death, and costs associated with it. It affects more than 2.2 million Americans.¹ Approximately 1 in 10 people over the age of 80 has atrial fibrillation, and for those over the age of 40, the lifetime risk of developing it is one in four.² Framingham data suggest that the risk of death is approximately twice as high for patients with atrial fibrillation compared with a similar cohort without.^3–5

IMPORTANT QUESTIONS DURING THE INITIAL WORKUP

Does the patient have a reversible cause of atrial fibrillation?

Atrial fibrillation is thought to be due to triggers that initiate it and to a myocardial substrate that supports it. While it may develop in the absence of other heart disease, it is often associated with hypertension, diabetes, obesity, structural heart disease (including congenital heart disease), obstructive sleep apnea, advanced age, and alcohol abuse.

Therefore, once atrial fibrillation has been diagnosed, the history, examination, and diagnostic workup should be directed toward looking for potentially reversible causes and for frequently associated comorbidities. Common reversible causes include:

Hyperthyroidism. The laboratory evaluation should include a thyrotropin (thyroid-stimulating hormone, or TSH) level.

Alcohol use, especially binge drinking.

Obstructive sleep apnea, if suspected on the basis of the history or the body habitus.

Structural heart disease such as valvular heart disease or congenital heart defects may also predispose to atrial fibrillation. Therefore, listen carefully to the heart and obtain a transthoracic echocardiogram if one has not already been done or if you suspect a change in valvular disease or systolic function since the most recent study.

How long has the patient been in atrial fibrillation?

The duration of the atrial fibrillation often affects the treatment strategy. Therefore, when the diagnosis has been made, it is important to try to estimate how long the patient has been in atrial fibrillation.

Often, we must settle for an estimate, as the patient’s recollection may be vague. However, in some cases, the symptoms are pronounced or electrocardiographic or telemetric data are available, allowing the time of onset to be clearly defined.

In addition, it is helpful to know if the patient has had prior episodes that were never brought to medical attention. To this end, elicit the patient’s spectrum of symptoms and encourage him or her to think back months or years and try to recall other times when similar symptoms might have occurred.

How do the symptoms affect the patient’s quality of life?

The clinician must also estimate the extent to which the symptoms affect the patient’s quality of life. This is best done when the heart rate is under control. If the patient still has significant symptoms despite adequate rate control, then a rhythm control strategy should probably be pursued.

MANAGING NEWLY DIAGNOSED ATRIAL FIBRILLATION

Control the heart rate with a beta-blocker, a calcium channel blocker, or digoxin

Many patients present during their first episode of atrial fibrillation with a rapid ventricular rate, especially if they are not already taking a drug to slow conduction through the atrioventricular node. If the symptoms are particularly profound, one should try to get the heart rate under control quickly.

Oral agents take time to be absorbed and are not always easy to titrate. Intravenous beta-blockers such as metoprolol (Lopressor) and labetalol (Normodyne, Trandate) or intravenous diltiazem (Cardizem) can slow the heart rate quickly and can be titrated. Once the heart rate is controlled, the oral form can be started, to allow weaning from the intravenous agent. In acute management, we seek a heart rate of less than about 100 to 110 beats per minute.

If the patient’s blood pressure is marginal, loading with intravenous digoxin may be considered. The dosage is 0.5 mg intravenously, then 0.25 mg intravenously in the first 6 hours and another 0.25 mg intravenously in another 6 hours. In patients with renal insufficiency the dosage should be less, or digoxin should be avoided altogether. Often, the blood pressure will improve once the heart rate is decreased, allowing other agents to be initiated. However, if the patient is frankly hypotensive with chest pain, shortness of breath, or a diminished level of consciousness, then emergency electrical cardioversion is indicated even if anticoagulation has not yet been started (more about anticoagulation below).

Oral forms of these same agents are the workhorses for heart rate control in the outpatient setting. Oral beta-blockers and nondihydropyridine calcium channel blockers (ie, diltiazem or verapamil [Calan, Verelan]) are the first-line agents, because when digoxin is used alone, it is relatively poor at controlling the heart rate, especially when the patient is not at rest.

The choice between these agents should be dictated by whether the patient has comorbidities such as coronary artery disease, heart failure, or reactive airway disease. Nondihydropyridine calcium channel blockers are relatively contraindicated in patients with heart failure, while beta-blockers can exacerbate reactive airway disease.⁶

It is also important to document that the heart rate is adequately controlled outside the hospital or outpatient clinic, where the patient is typically sitting or supine. This can be done with a 6-minute walk, exercise test, or Holter monitor once rate-controlling agents have been titrated.⁷

When atrial fibrillation is first diagnosed, it may not be possible to determine if it is paroxysmal (ie, self-terminating) or persistent. If the episode does not quickly end on its own, consideration may be given to restoring sinus rhythm.

Although experts debate the merits of a rate control approach vs a rhythm control approach for managing atrial fibrillation in the long term, many, including ourselves, recommend trying to restore sinus rhythm at least once when atrial fibrillation is first discovered. It is not always clear if atrial fibrillation is truly asymptomatic. Symptoms such as fatigue or decreased exercise tolerance can be subtle. Additionally, these symptoms may be attributed to other factors such as deconditioning, obesity, or advancing age. Thus, in many cases, only restoring normal sinus rhythm for a time allows the patient and clinician to fully assess the symptoms attributable to atrial fibrillation.

Therefore, in patients with newly diagnosed atrial fibrillation, an attempt to restore sinus rhythm is often warranted. Exceptions are in select patients who have no apparent symptoms and who are very old or are deemed too frail to tolerate cardioversion.

Direct-current cardioversion is typically the treatment of choice when attempting to restore sinus rhythm. The procedure can be done without anticoagulation within 48 hours of the onset of atrial fibrillation, if the time of onset is clear.⁷ However, clinicians must be careful in defining the onset of atrial fibrillation for this purpose.

Symptoms such as fatigue or shortness of breath can be vague in terms of the exact time of onset and often cannot be relied upon for the purpose of deciding whether cardioversion can be done without anticoagulation. When in doubt, it is best to err on the side of safety and assume that the atrial fibrillation has been going on for more than 48 hours.

If the time of onset is unclear or if more than 48 hours have passed, there are two general strategies for proceeding to electrical cardioversion.

One is to order transesophageal echocardiography and begin anticoagulation therapy at the same time. If there is no thrombus in the left atrium, then cardioversion can be done.⁸ Therapeutic anticoagulation with heparin, low-molecular-weight heparin, or warfarin (Coumadin) should be achieved within 24 to 48 hours of transesophageal echocardiography and cardioversion to minimize the risk of thromboembolic events, which can occur even after sinus rhythm has been restored.

At our institution, we typically strive to achieve therapeutic anticoagulation with either heparin or low-molecular-weight heparin before cardioversion in this scenario so as to avoid situations in which a patient may undergo cardioversion but then fail to achieve therapeutic anticoagulation for some time due to unforeseen factors.

The other approach is to start warfarin and maintain a goal international normalized ratio (INR) of 2 to 3 for 3 weeks, at which time cardioversion can be performed safely without transesophageal echocardiography.⁸

Regardless of which strategy is used, anticoagulation should be continued for at least 4 weeks after cardioversion,⁸ as atrial dysfunction and the risk of stroke may persist for days to weeks after normal sinus rhythm is restored.⁹

Role of antiarrhythmic drugs

Antiarrhythmic drugs can be used for chemical cardioversion or, more often, to help maintain sinus rhythm after direct-current cardioversion.

Because most of these drugs have at least a small chance of restoring normal sinus rhythm, we need to follow the same rules when starting them as when performing direct-current cardioversion. Patients should not be started on an antiarrhythmic medication until they have had adequate anticoagulation for at least 3 weeks or adequate anticoagulation and a transesophageal echocardiogram confirming that there is no thrombus in the left atrium.

Antiarrhythmic drugs should be started in select patients with newly diagnosed atrial fibrillation in whom a rhythm control strategy will be pursued. For patients whose history suggests a single episode, or episodes that previously self-terminated, an antiarrhythmic may not be necessary. For those with frequent episodes or whose history suggests ongoing atrial fibrillation for a long period, an antiarrhythmic will likely be required to provide a reasonable chance of achieving freedom from atrial fibrillation.

The choice of antiarrhythmic drug should be tailored to the specific patient.

Propafenone (Rythmol) and flecainide (Tambocor) are first-line drugs⁷ but are contraindicated in patients with coronary artery disease and significant structural heart disease.¹⁰

Sotalol (Betapace) and dofetilide (Tikosyn) can be used in patients with coronary artery disease. However, sotalol is contraindicated in patients with congestive heart failure, and dofetilide carries a long list of drug interactions. Both must be used with extreme caution in patients with renal insufficiency, and hospital admission is required for initiation or upward titration of the dose.

Amiodarone (Cordarone) is effective, and in the short term it is typically very well tolerated. However, it has a long half-life, and its potential for long-term toxicity often makes it a poor choice for long-term treatment. The toxicity of amiodarone increases with the cumulative dose. Therefore, this drug should be avoided for long-term therapy of atrial fibrillation in younger patients.

The ‘pill-in-the-pocket’ strategy

The “pill-in-the-pocket” strategy, in which patients are instructed to take their medication only when they have a bout of atrial fibrillation, is a reasonable option for patients with symptomatic recurrences of paroxysmal atrial fibrillation. This strategy is mainly reserved for patients who have relatively infrequent recurrences. Those who have frequent recurrences are usually more effectively treated with daily dosing of an antiarrhythmic. Flecainide and propafenone are the agents of choice for this approach because of their safety profile and efficacy in chemical cardioversion.

While this strategy may be started on an outpatient basis in patients with lone, paroxysmal atrial fibrillation, those with structural heart disease or conduction abnormalities should be observed in the hospital during initiation of therapy to observe for excessive PR prolongation or development of dangerous or worrisome arrhythmias.^11–13

Additionally, these agents can decrease the refractory period of the atrioventricular node, thereby increasing the ventricular rate. In the case of atrial flutter, patients may be converted from variable or 2:1 response to a 1:1 conduction. Thus, one should consider also using a beta-blocker with this strategy.

Since the goal of this approach is to convert the patient to sinus rhythm within a few hours of the onset of atrial fibrillation, it may be implemented without the use of warfarin. Patients are instructed that if they do not convert to normal sinus rhythm within a few hours, they should notify the physician so they can undergo electrical cardioversion within the 48-hour window from the onset of atrial fibrillation.

Dronedarone, a new antiarrhythmic drug

Dronedarone (Multaq) is now available and has been shown to be effective in treating atrial fibrillation.¹⁴ It has a long half-life and a mechanism of action similar to that of amiodarone. However, it may be inferior to amiodarone in terms of efficacy.¹⁵ It is metabolized by CYP3A4. No dosage adjustment is needed for patients with renal insufficiency.

Because dronedarone lacks the iodine moiety found in amiodarone, it should not carry the same toxicity profile. No pulmonary or thyroid toxicity was reported in early trials.¹⁶

Nevertheless, dronedarone has several important limitations. It carries a black box warning stating it is contraindicated in patients with severe or recently decompensated heart failure, as the mortality rate was twice as high when this drug was used in such patients in initial studies.¹⁷ Additionally, there have been reports of hepatotoxicity requiring liver transplantation in a small number of patients. The extent of this problem and strategies for avoiding it are not yet defined as of the writing of this paper. As with any new medication, patients who are started on dronedarone should be observed closely for any side effects, and these should be reported to assist in the development of the drug’s safety profile.

In a procedure that can potentially cure atrial fibrillation, catheters are inserted into the left atrium and rings of scar tissue are created around the ostia of the pulmonary veins using radiofrequency energy, electrically isolating them from the rest of the left atrium.

Some debate exists as to whether this procedure may be reasonable as a first-line therapy for some patients with atrial fibrillation.^18,19 It may be considered as an early treatment strategy in a small subset of patients, specifically young patients with symptomatic, recurrent atrial fibrillation, especially if they are averse to long-term antiarrhythmic therapy.

Because patients may still be more prone to atrial arrhythmias for several weeks to months after the procedure, they must be able to tolerate anticoagulation with warfarin for at least several months.

Rate control vs rhythm control

The choice between a rate control strategy or a rhythm control strategy in the long term is not always straightforward. While atrial fibrillation is clearly associated with higher morbidity and mortality rates, there are few data to date showing that restoring and maintaining sinus rhythm in patients with atrial fibrillation reduce the incidence of morbid complications or the likelihood of death.

Thus, current guidelines recommend a rate control strategy in patients who have no symptoms, and a rhythm control strategy if rate control cannot be achieved or if symptoms persist despite adequate control of the heart rate.⁷ The circumstances and preferences of the individual patient should carry weight in this decision.

Trials are under way that may shed more light on the relative benefits of rhythm control with ablation or antiarrhythmics and rate control.

PREVENTING THROMBOEMBOLIC EVENTS

Warfarin

In the short term, warfarin therapy may be dictated by plans to restore sinus rhythm. Patients need warfarin for at least 4 weeks after cardioversion unless it is performed within 48 hours of the onset of atrial fibrillation.

The CHADS₂score (1 point each for congestive heart failure, hypertension, age 75 or older, and diabetes mellitus; 2 points for prior stroke or transient ischemic attack) is useful when deciding whether to give long-term anticoagulation.

For patients with a score of 0, the risk of stroke is lower than the risk of a major bleeding complication while on therapeutic warfarin.^20,21 For these patients, aspirin 81 to 325 mg daily is recommended for stroke prophylaxis.

For those with a score of 2 or greater, the risk of stroke without warfarin is greater than the risk of a major bleeding complication with warfarin. These patients should receive warfarin with a goal INR of 2.0 to 3.0.⁷

Patients with a CHADS₂ score of 1 present a dilemma, as their risk of stroke without warfarin is about the same as their risk of a major bleeding complication with warfarin. They can be managed with either warfarin or aspirin, according to the physician’s judgment.⁷ In these cases, factors such as hobbies or professions that might increase the risk of bleeding, perceived frequency of atrial fibrillation episodes, and even patient preconceptions about warfarin are often used when deciding between aspirin and warfarin.

Patients with a CHADS₂ score of 2 or greater with a single episode of atrial fibrillation and a likely reversible cause may also pose a dilemma when deciding whether to start warfarin. These patients have demonstrated they at least have the substrate to maintain atrial fibrillation. This situation again calls for physician judgment. Bear in mind that asymptomatic recurrences are common in patients with atrial fibrillation.^22,23 A higher CHADS₂ score denotes a greater risk of stroke and may influence this decision. It is usually beneficial to enlist the patient in this decision-making process, as patients often have very strong opinions about tolerance of the risk of stroke or of warfarin therapy itself.

Another strategy is to start anticoagulation with warfarin and aggressively monitor for recurrences. If the patient has no recurrences of atrial fibrillation after 6 to 12 months and the reversible cause is resolved, one can then revisit the need for warfarin.

Role of aspirin and clopidogrel

Aspirin, alone or in conjunction with clopidogrel (Plavix), may provide an alternative for stroke prophylaxis in patients in whom warfarin is contraindicated. While inferior to warfarin, the combination of aspirin and clopidogrel has been shown to decrease the incidence of major thromboembolic events, especially stroke.²⁴ However, the risk of a major bleeding complication was also significantly increased.

This combination may be a reasonable strategy in select patients with a CHADS₂ score of 2 or greater in whom warfarin cannot be used for reasons such as personal aversion to the medication, side effects, or nonbleeding complications or in patients whose INR is exceedingly difficult to keep within the therapeutic range.

Dabigatran, a new anticoagulant

The newest option for anticoagulation in patients with atrial fibrillation is a direct thrombin inhibitor, dabigatran (Pradaxa).

In the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial,²⁵ dabigatran was studied head-to-head with warfarin. The doses of dabigatran studied were 110 mg and 150 mg twice a day. At 150 mg twice a day, patients on dabigatran had a lower rate of stroke than with warfarin (1.11% vs 1.69%, P < .001), as well as a lower rate of central nervous system bleeding (0.10% vs 0.38% with warfarin, P < .001). The rates of major bleeding were comparable in the patients receiving warfarin or dabigatran 150 mg twice a day, but the rate of gastrointestinal bleeding was higher in the dabigatran group (1.51% vs 1.02% with warfarin, P < .001).²⁵

Dabigatran was recently approved by the US Food and Drug Administration for use in patients with atrial fibrillation. Doses of 150 mg and 75 mg are available.

Dabigatran is renally excreted, and the 150 mg twice-a-day dosing is intended for patients with a creatinine clearance greater than 30 mL/min. The 75-mg twice-a-day dosing is intended for patients with a creatinine clearance of 15 to 30 mL/min. However, it should be noted that currently there are no data to support the 75-mg twice-a-day dosing.

Dabigatran does have several advantages over warfarin. Patients do not need to avoid foods containing vitamin K, and routine serial monitoring does not appear to be needed. As with any new medication, patients who are started on dabigatran should be observed closely for any side effects, and these should be reported to assist in the development of the drug’s safety profile.

SPECIAL CIRCUMSTANCES

After cardiac or noncardiac surgery

Atrial fibrillation is common after open heart surgery, occurring in approximately 25% to 50% of patients.^26–28

When this happens, at least one or two attempts are made to restore sinus rhythm. Especially in the early postoperative period, anticoagulation with heparin or warfarin may be contraindicated, so careful attention must be paid to the patient’s heart rhythm so that atrial fibrillation can be recognized quickly and cardioversion performed within a 48-hour window of onset. Beta-blockers, diltiazem, and verapamil are typically used for rate control.

When atrial fibrillation recurs in patients who have undergone open heart surgery, antiarrhythmics are started early to help prevent further recurrences. At our institution, we usually use amiodarone, as it is highly effective and well tolerated in the short term. When started on amiodarone for postoperative atrial fibrillation, patients are informed that the drug will be stopped after about 2 to 3 months. For patients who continue to have bouts of atrial fibrillation, the need for antiarrhythmic medications can be reassessed, and, if needed, the optimal antiarrhythmic medication for long-term therapy for the patient can be chosen.

Atrial fibrillation in severe, acute illness

Atrial fibrillation is common in the setting of extreme systemic stressors such as shock and sepsis and when the patient is being supported with inotropic agents. In this setting, patients may be in a high-catecholamine state, and both the heart rate and the heart rhythm may be very difficult to control.

Beta-blockers and nondihydropyridine calcium channel blockers should not be used when patients are on medications to support blood pressure, and in this setting, when the patient’s hemodynamic status permits the use of these agents, their effect may be minimal.

Amiodarone or perhaps digoxin may slow the heart rate somewhat without too much effect on the blood pressure. However, with amiodarone, one may have to accept a risk of chemical cardioversion.

Electrical cardioversion with or without the assistance of an antiarrhythmic drug may control the heart rate by restoring sinus rhythm. However, atrial fibrillation often recurs, and if it recurs quickly one may have to accept elevated heart rates until the underlying process is addressed.

Three general concerns dictate the management of atrial fibrillation:

• Controlling the heart rate
• Controlling symptoms
• Preventing thromboembolic events, including stroke.

When seeing a patient with newly diagnosed atrial fibrillation, these same three concerns should be kept in mind, but several additional issues must be addressed:

• Reversible causes of atrial fibrillation must be ruled out
• The true time of onset of the atrial fibrillation and the frequency of the episodes should be ascertained, if possible
• A careful estimation of the patient’s symptom burden should be made.

Atrial fibrillation is common and has a huge impact in terms of the morbidity, death, and costs associated with it. It affects more than 2.2 million Americans.¹ Approximately 1 in 10 people over the age of 80 has atrial fibrillation, and for those over the age of 40, the lifetime risk of developing it is one in four.² Framingham data suggest that the risk of death is approximately twice as high for patients with atrial fibrillation compared with a similar cohort without.^3–5

IMPORTANT QUESTIONS DURING THE INITIAL WORKUP

Does the patient have a reversible cause of atrial fibrillation?

Atrial fibrillation is thought to be due to triggers that initiate it and to a myocardial substrate that supports it. While it may develop in the absence of other heart disease, it is often associated with hypertension, diabetes, obesity, structural heart disease (including congenital heart disease), obstructive sleep apnea, advanced age, and alcohol abuse.

Therefore, once atrial fibrillation has been diagnosed, the history, examination, and diagnostic workup should be directed toward looking for potentially reversible causes and for frequently associated comorbidities. Common reversible causes include:

Hyperthyroidism. The laboratory evaluation should include a thyrotropin (thyroid-stimulating hormone, or TSH) level.

Alcohol use, especially binge drinking.

Obstructive sleep apnea, if suspected on the basis of the history or the body habitus.

Structural heart disease such as valvular heart disease or congenital heart defects may also predispose to atrial fibrillation. Therefore, listen carefully to the heart and obtain a transthoracic echocardiogram if one has not already been done or if you suspect a change in valvular disease or systolic function since the most recent study.

How long has the patient been in atrial fibrillation?

The duration of the atrial fibrillation often affects the treatment strategy. Therefore, when the diagnosis has been made, it is important to try to estimate how long the patient has been in atrial fibrillation.

Often, we must settle for an estimate, as the patient’s recollection may be vague. However, in some cases, the symptoms are pronounced or electrocardiographic or telemetric data are available, allowing the time of onset to be clearly defined.

In addition, it is helpful to know if the patient has had prior episodes that were never brought to medical attention. To this end, elicit the patient’s spectrum of symptoms and encourage him or her to think back months or years and try to recall other times when similar symptoms might have occurred.

How do the symptoms affect the patient’s quality of life?

The clinician must also estimate the extent to which the symptoms affect the patient’s quality of life. This is best done when the heart rate is under control. If the patient still has significant symptoms despite adequate rate control, then a rhythm control strategy should probably be pursued.

MANAGING NEWLY DIAGNOSED ATRIAL FIBRILLATION

Control the heart rate with a beta-blocker, a calcium channel blocker, or digoxin

Many patients present during their first episode of atrial fibrillation with a rapid ventricular rate, especially if they are not already taking a drug to slow conduction through the atrioventricular node. If the symptoms are particularly profound, one should try to get the heart rate under control quickly.

Oral agents take time to be absorbed and are not always easy to titrate. Intravenous beta-blockers such as metoprolol (Lopressor) and labetalol (Normodyne, Trandate) or intravenous diltiazem (Cardizem) can slow the heart rate quickly and can be titrated. Once the heart rate is controlled, the oral form can be started, to allow weaning from the intravenous agent. In acute management, we seek a heart rate of less than about 100 to 110 beats per minute.

If the patient’s blood pressure is marginal, loading with intravenous digoxin may be considered. The dosage is 0.5 mg intravenously, then 0.25 mg intravenously in the first 6 hours and another 0.25 mg intravenously in another 6 hours. In patients with renal insufficiency the dosage should be less, or digoxin should be avoided altogether. Often, the blood pressure will improve once the heart rate is decreased, allowing other agents to be initiated. However, if the patient is frankly hypotensive with chest pain, shortness of breath, or a diminished level of consciousness, then emergency electrical cardioversion is indicated even if anticoagulation has not yet been started (more about anticoagulation below).

Oral forms of these same agents are the workhorses for heart rate control in the outpatient setting. Oral beta-blockers and nondihydropyridine calcium channel blockers (ie, diltiazem or verapamil [Calan, Verelan]) are the first-line agents, because when digoxin is used alone, it is relatively poor at controlling the heart rate, especially when the patient is not at rest.

The choice between these agents should be dictated by whether the patient has comorbidities such as coronary artery disease, heart failure, or reactive airway disease. Nondihydropyridine calcium channel blockers are relatively contraindicated in patients with heart failure, while beta-blockers can exacerbate reactive airway disease.⁶

It is also important to document that the heart rate is adequately controlled outside the hospital or outpatient clinic, where the patient is typically sitting or supine. This can be done with a 6-minute walk, exercise test, or Holter monitor once rate-controlling agents have been titrated.⁷

When atrial fibrillation is first diagnosed, it may not be possible to determine if it is paroxysmal (ie, self-terminating) or persistent. If the episode does not quickly end on its own, consideration may be given to restoring sinus rhythm.

Although experts debate the merits of a rate control approach vs a rhythm control approach for managing atrial fibrillation in the long term, many, including ourselves, recommend trying to restore sinus rhythm at least once when atrial fibrillation is first discovered. It is not always clear if atrial fibrillation is truly asymptomatic. Symptoms such as fatigue or decreased exercise tolerance can be subtle. Additionally, these symptoms may be attributed to other factors such as deconditioning, obesity, or advancing age. Thus, in many cases, only restoring normal sinus rhythm for a time allows the patient and clinician to fully assess the symptoms attributable to atrial fibrillation.

Therefore, in patients with newly diagnosed atrial fibrillation, an attempt to restore sinus rhythm is often warranted. Exceptions are in select patients who have no apparent symptoms and who are very old or are deemed too frail to tolerate cardioversion.

Direct-current cardioversion is typically the treatment of choice when attempting to restore sinus rhythm. The procedure can be done without anticoagulation within 48 hours of the onset of atrial fibrillation, if the time of onset is clear.⁷ However, clinicians must be careful in defining the onset of atrial fibrillation for this purpose.

Symptoms such as fatigue or shortness of breath can be vague in terms of the exact time of onset and often cannot be relied upon for the purpose of deciding whether cardioversion can be done without anticoagulation. When in doubt, it is best to err on the side of safety and assume that the atrial fibrillation has been going on for more than 48 hours.

If the time of onset is unclear or if more than 48 hours have passed, there are two general strategies for proceeding to electrical cardioversion.

One is to order transesophageal echocardiography and begin anticoagulation therapy at the same time. If there is no thrombus in the left atrium, then cardioversion can be done.⁸ Therapeutic anticoagulation with heparin, low-molecular-weight heparin, or warfarin (Coumadin) should be achieved within 24 to 48 hours of transesophageal echocardiography and cardioversion to minimize the risk of thromboembolic events, which can occur even after sinus rhythm has been restored.

At our institution, we typically strive to achieve therapeutic anticoagulation with either heparin or low-molecular-weight heparin before cardioversion in this scenario so as to avoid situations in which a patient may undergo cardioversion but then fail to achieve therapeutic anticoagulation for some time due to unforeseen factors.

The other approach is to start warfarin and maintain a goal international normalized ratio (INR) of 2 to 3 for 3 weeks, at which time cardioversion can be performed safely without transesophageal echocardiography.⁸

Regardless of which strategy is used, anticoagulation should be continued for at least 4 weeks after cardioversion,⁸ as atrial dysfunction and the risk of stroke may persist for days to weeks after normal sinus rhythm is restored.⁹

Role of antiarrhythmic drugs

Antiarrhythmic drugs can be used for chemical cardioversion or, more often, to help maintain sinus rhythm after direct-current cardioversion.

Because most of these drugs have at least a small chance of restoring normal sinus rhythm, we need to follow the same rules when starting them as when performing direct-current cardioversion. Patients should not be started on an antiarrhythmic medication until they have had adequate anticoagulation for at least 3 weeks or adequate anticoagulation and a transesophageal echocardiogram confirming that there is no thrombus in the left atrium.

Antiarrhythmic drugs should be started in select patients with newly diagnosed atrial fibrillation in whom a rhythm control strategy will be pursued. For patients whose history suggests a single episode, or episodes that previously self-terminated, an antiarrhythmic may not be necessary. For those with frequent episodes or whose history suggests ongoing atrial fibrillation for a long period, an antiarrhythmic will likely be required to provide a reasonable chance of achieving freedom from atrial fibrillation.

The choice of antiarrhythmic drug should be tailored to the specific patient.

Propafenone (Rythmol) and flecainide (Tambocor) are first-line drugs⁷ but are contraindicated in patients with coronary artery disease and significant structural heart disease.¹⁰

Sotalol (Betapace) and dofetilide (Tikosyn) can be used in patients with coronary artery disease. However, sotalol is contraindicated in patients with congestive heart failure, and dofetilide carries a long list of drug interactions. Both must be used with extreme caution in patients with renal insufficiency, and hospital admission is required for initiation or upward titration of the dose.

Amiodarone (Cordarone) is effective, and in the short term it is typically very well tolerated. However, it has a long half-life, and its potential for long-term toxicity often makes it a poor choice for long-term treatment. The toxicity of amiodarone increases with the cumulative dose. Therefore, this drug should be avoided for long-term therapy of atrial fibrillation in younger patients.

The ‘pill-in-the-pocket’ strategy

The “pill-in-the-pocket” strategy, in which patients are instructed to take their medication only when they have a bout of atrial fibrillation, is a reasonable option for patients with symptomatic recurrences of paroxysmal atrial fibrillation. This strategy is mainly reserved for patients who have relatively infrequent recurrences. Those who have frequent recurrences are usually more effectively treated with daily dosing of an antiarrhythmic. Flecainide and propafenone are the agents of choice for this approach because of their safety profile and efficacy in chemical cardioversion.

While this strategy may be started on an outpatient basis in patients with lone, paroxysmal atrial fibrillation, those with structural heart disease or conduction abnormalities should be observed in the hospital during initiation of therapy to observe for excessive PR prolongation or development of dangerous or worrisome arrhythmias.^11–13

Additionally, these agents can decrease the refractory period of the atrioventricular node, thereby increasing the ventricular rate. In the case of atrial flutter, patients may be converted from variable or 2:1 response to a 1:1 conduction. Thus, one should consider also using a beta-blocker with this strategy.

Since the goal of this approach is to convert the patient to sinus rhythm within a few hours of the onset of atrial fibrillation, it may be implemented without the use of warfarin. Patients are instructed that if they do not convert to normal sinus rhythm within a few hours, they should notify the physician so they can undergo electrical cardioversion within the 48-hour window from the onset of atrial fibrillation.

Dronedarone, a new antiarrhythmic drug

Dronedarone (Multaq) is now available and has been shown to be effective in treating atrial fibrillation.¹⁴ It has a long half-life and a mechanism of action similar to that of amiodarone. However, it may be inferior to amiodarone in terms of efficacy.¹⁵ It is metabolized by CYP3A4. No dosage adjustment is needed for patients with renal insufficiency.

Because dronedarone lacks the iodine moiety found in amiodarone, it should not carry the same toxicity profile. No pulmonary or thyroid toxicity was reported in early trials.¹⁶

Nevertheless, dronedarone has several important limitations. It carries a black box warning stating it is contraindicated in patients with severe or recently decompensated heart failure, as the mortality rate was twice as high when this drug was used in such patients in initial studies.¹⁷ Additionally, there have been reports of hepatotoxicity requiring liver transplantation in a small number of patients. The extent of this problem and strategies for avoiding it are not yet defined as of the writing of this paper. As with any new medication, patients who are started on dronedarone should be observed closely for any side effects, and these should be reported to assist in the development of the drug’s safety profile.

In a procedure that can potentially cure atrial fibrillation, catheters are inserted into the left atrium and rings of scar tissue are created around the ostia of the pulmonary veins using radiofrequency energy, electrically isolating them from the rest of the left atrium.

Some debate exists as to whether this procedure may be reasonable as a first-line therapy for some patients with atrial fibrillation.^18,19 It may be considered as an early treatment strategy in a small subset of patients, specifically young patients with symptomatic, recurrent atrial fibrillation, especially if they are averse to long-term antiarrhythmic therapy.

Because patients may still be more prone to atrial arrhythmias for several weeks to months after the procedure, they must be able to tolerate anticoagulation with warfarin for at least several months.

Rate control vs rhythm control

The choice between a rate control strategy or a rhythm control strategy in the long term is not always straightforward. While atrial fibrillation is clearly associated with higher morbidity and mortality rates, there are few data to date showing that restoring and maintaining sinus rhythm in patients with atrial fibrillation reduce the incidence of morbid complications or the likelihood of death.

Thus, current guidelines recommend a rate control strategy in patients who have no symptoms, and a rhythm control strategy if rate control cannot be achieved or if symptoms persist despite adequate control of the heart rate.⁷ The circumstances and preferences of the individual patient should carry weight in this decision.

Trials are under way that may shed more light on the relative benefits of rhythm control with ablation or antiarrhythmics and rate control.

PREVENTING THROMBOEMBOLIC EVENTS

Warfarin

In the short term, warfarin therapy may be dictated by plans to restore sinus rhythm. Patients need warfarin for at least 4 weeks after cardioversion unless it is performed within 48 hours of the onset of atrial fibrillation.

The CHADS₂score (1 point each for congestive heart failure, hypertension, age 75 or older, and diabetes mellitus; 2 points for prior stroke or transient ischemic attack) is useful when deciding whether to give long-term anticoagulation.

For patients with a score of 0, the risk of stroke is lower than the risk of a major bleeding complication while on therapeutic warfarin.^20,21 For these patients, aspirin 81 to 325 mg daily is recommended for stroke prophylaxis.

For those with a score of 2 or greater, the risk of stroke without warfarin is greater than the risk of a major bleeding complication with warfarin. These patients should receive warfarin with a goal INR of 2.0 to 3.0.⁷

Patients with a CHADS₂ score of 1 present a dilemma, as their risk of stroke without warfarin is about the same as their risk of a major bleeding complication with warfarin. They can be managed with either warfarin or aspirin, according to the physician’s judgment.⁷ In these cases, factors such as hobbies or professions that might increase the risk of bleeding, perceived frequency of atrial fibrillation episodes, and even patient preconceptions about warfarin are often used when deciding between aspirin and warfarin.

Patients with a CHADS₂ score of 2 or greater with a single episode of atrial fibrillation and a likely reversible cause may also pose a dilemma when deciding whether to start warfarin. These patients have demonstrated they at least have the substrate to maintain atrial fibrillation. This situation again calls for physician judgment. Bear in mind that asymptomatic recurrences are common in patients with atrial fibrillation.^22,23 A higher CHADS₂ score denotes a greater risk of stroke and may influence this decision. It is usually beneficial to enlist the patient in this decision-making process, as patients often have very strong opinions about tolerance of the risk of stroke or of warfarin therapy itself.

Another strategy is to start anticoagulation with warfarin and aggressively monitor for recurrences. If the patient has no recurrences of atrial fibrillation after 6 to 12 months and the reversible cause is resolved, one can then revisit the need for warfarin.

Role of aspirin and clopidogrel

Aspirin, alone or in conjunction with clopidogrel (Plavix), may provide an alternative for stroke prophylaxis in patients in whom warfarin is contraindicated. While inferior to warfarin, the combination of aspirin and clopidogrel has been shown to decrease the incidence of major thromboembolic events, especially stroke.²⁴ However, the risk of a major bleeding complication was also significantly increased.

This combination may be a reasonable strategy in select patients with a CHADS₂ score of 2 or greater in whom warfarin cannot be used for reasons such as personal aversion to the medication, side effects, or nonbleeding complications or in patients whose INR is exceedingly difficult to keep within the therapeutic range.

Dabigatran, a new anticoagulant

The newest option for anticoagulation in patients with atrial fibrillation is a direct thrombin inhibitor, dabigatran (Pradaxa).

In the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial,²⁵ dabigatran was studied head-to-head with warfarin. The doses of dabigatran studied were 110 mg and 150 mg twice a day. At 150 mg twice a day, patients on dabigatran had a lower rate of stroke than with warfarin (1.11% vs 1.69%, P < .001), as well as a lower rate of central nervous system bleeding (0.10% vs 0.38% with warfarin, P < .001). The rates of major bleeding were comparable in the patients receiving warfarin or dabigatran 150 mg twice a day, but the rate of gastrointestinal bleeding was higher in the dabigatran group (1.51% vs 1.02% with warfarin, P < .001).²⁵

Dabigatran was recently approved by the US Food and Drug Administration for use in patients with atrial fibrillation. Doses of 150 mg and 75 mg are available.

Dabigatran is renally excreted, and the 150 mg twice-a-day dosing is intended for patients with a creatinine clearance greater than 30 mL/min. The 75-mg twice-a-day dosing is intended for patients with a creatinine clearance of 15 to 30 mL/min. However, it should be noted that currently there are no data to support the 75-mg twice-a-day dosing.

Dabigatran does have several advantages over warfarin. Patients do not need to avoid foods containing vitamin K, and routine serial monitoring does not appear to be needed. As with any new medication, patients who are started on dabigatran should be observed closely for any side effects, and these should be reported to assist in the development of the drug’s safety profile.

SPECIAL CIRCUMSTANCES

After cardiac or noncardiac surgery

Atrial fibrillation is common after open heart surgery, occurring in approximately 25% to 50% of patients.^26–28

When this happens, at least one or two attempts are made to restore sinus rhythm. Especially in the early postoperative period, anticoagulation with heparin or warfarin may be contraindicated, so careful attention must be paid to the patient’s heart rhythm so that atrial fibrillation can be recognized quickly and cardioversion performed within a 48-hour window of onset. Beta-blockers, diltiazem, and verapamil are typically used for rate control.

When atrial fibrillation recurs in patients who have undergone open heart surgery, antiarrhythmics are started early to help prevent further recurrences. At our institution, we usually use amiodarone, as it is highly effective and well tolerated in the short term. When started on amiodarone for postoperative atrial fibrillation, patients are informed that the drug will be stopped after about 2 to 3 months. For patients who continue to have bouts of atrial fibrillation, the need for antiarrhythmic medications can be reassessed, and, if needed, the optimal antiarrhythmic medication for long-term therapy for the patient can be chosen.

Atrial fibrillation in severe, acute illness

Atrial fibrillation is common in the setting of extreme systemic stressors such as shock and sepsis and when the patient is being supported with inotropic agents. In this setting, patients may be in a high-catecholamine state, and both the heart rate and the heart rhythm may be very difficult to control.

Beta-blockers and nondihydropyridine calcium channel blockers should not be used when patients are on medications to support blood pressure, and in this setting, when the patient’s hemodynamic status permits the use of these agents, their effect may be minimal.

Amiodarone or perhaps digoxin may slow the heart rate somewhat without too much effect on the blood pressure. However, with amiodarone, one may have to accept a risk of chemical cardioversion.

Electrical cardioversion with or without the assistance of an antiarrhythmic drug may control the heart rate by restoring sinus rhythm. However, atrial fibrillation often recurs, and if it recurs quickly one may have to accept elevated heart rates until the underlying process is addressed.

Three general concerns dictate the management of atrial fibrillation:

• Controlling the heart rate
• Controlling symptoms
• Preventing thromboembolic events, including stroke.

When seeing a patient with newly diagnosed atrial fibrillation, these same three concerns should be kept in mind, but several additional issues must be addressed:

• Reversible causes of atrial fibrillation must be ruled out
• The true time of onset of the atrial fibrillation and the frequency of the episodes should be ascertained, if possible
• A careful estimation of the patient’s symptom burden should be made.

Atrial fibrillation is common and has a huge impact in terms of the morbidity, death, and costs associated with it. It affects more than 2.2 million Americans.¹ Approximately 1 in 10 people over the age of 80 has atrial fibrillation, and for those over the age of 40, the lifetime risk of developing it is one in four.² Framingham data suggest that the risk of death is approximately twice as high for patients with atrial fibrillation compared with a similar cohort without.^3–5

IMPORTANT QUESTIONS DURING THE INITIAL WORKUP

Does the patient have a reversible cause of atrial fibrillation?

Atrial fibrillation is thought to be due to triggers that initiate it and to a myocardial substrate that supports it. While it may develop in the absence of other heart disease, it is often associated with hypertension, diabetes, obesity, structural heart disease (including congenital heart disease), obstructive sleep apnea, advanced age, and alcohol abuse.

Therefore, once atrial fibrillation has been diagnosed, the history, examination, and diagnostic workup should be directed toward looking for potentially reversible causes and for frequently associated comorbidities. Common reversible causes include:

Hyperthyroidism. The laboratory evaluation should include a thyrotropin (thyroid-stimulating hormone, or TSH) level.

Alcohol use, especially binge drinking.

Obstructive sleep apnea, if suspected on the basis of the history or the body habitus.

Structural heart disease such as valvular heart disease or congenital heart defects may also predispose to atrial fibrillation. Therefore, listen carefully to the heart and obtain a transthoracic echocardiogram if one has not already been done or if you suspect a change in valvular disease or systolic function since the most recent study.

How long has the patient been in atrial fibrillation?

The duration of the atrial fibrillation often affects the treatment strategy. Therefore, when the diagnosis has been made, it is important to try to estimate how long the patient has been in atrial fibrillation.

Often, we must settle for an estimate, as the patient’s recollection may be vague. However, in some cases, the symptoms are pronounced or electrocardiographic or telemetric data are available, allowing the time of onset to be clearly defined.

In addition, it is helpful to know if the patient has had prior episodes that were never brought to medical attention. To this end, elicit the patient’s spectrum of symptoms and encourage him or her to think back months or years and try to recall other times when similar symptoms might have occurred.

How do the symptoms affect the patient’s quality of life?

The clinician must also estimate the extent to which the symptoms affect the patient’s quality of life. This is best done when the heart rate is under control. If the patient still has significant symptoms despite adequate rate control, then a rhythm control strategy should probably be pursued.

MANAGING NEWLY DIAGNOSED ATRIAL FIBRILLATION

Control the heart rate with a beta-blocker, a calcium channel blocker, or digoxin

Many patients present during their first episode of atrial fibrillation with a rapid ventricular rate, especially if they are not already taking a drug to slow conduction through the atrioventricular node. If the symptoms are particularly profound, one should try to get the heart rate under control quickly.

Oral agents take time to be absorbed and are not always easy to titrate. Intravenous beta-blockers such as metoprolol (Lopressor) and labetalol (Normodyne, Trandate) or intravenous diltiazem (Cardizem) can slow the heart rate quickly and can be titrated. Once the heart rate is controlled, the oral form can be started, to allow weaning from the intravenous agent. In acute management, we seek a heart rate of less than about 100 to 110 beats per minute.

If the patient’s blood pressure is marginal, loading with intravenous digoxin may be considered. The dosage is 0.5 mg intravenously, then 0.25 mg intravenously in the first 6 hours and another 0.25 mg intravenously in another 6 hours. In patients with renal insufficiency the dosage should be less, or digoxin should be avoided altogether. Often, the blood pressure will improve once the heart rate is decreased, allowing other agents to be initiated. However, if the patient is frankly hypotensive with chest pain, shortness of breath, or a diminished level of consciousness, then emergency electrical cardioversion is indicated even if anticoagulation has not yet been started (more about anticoagulation below).

Oral forms of these same agents are the workhorses for heart rate control in the outpatient setting. Oral beta-blockers and nondihydropyridine calcium channel blockers (ie, diltiazem or verapamil [Calan, Verelan]) are the first-line agents, because when digoxin is used alone, it is relatively poor at controlling the heart rate, especially when the patient is not at rest.

The choice between these agents should be dictated by whether the patient has comorbidities such as coronary artery disease, heart failure, or reactive airway disease. Nondihydropyridine calcium channel blockers are relatively contraindicated in patients with heart failure, while beta-blockers can exacerbate reactive airway disease.⁶

It is also important to document that the heart rate is adequately controlled outside the hospital or outpatient clinic, where the patient is typically sitting or supine. This can be done with a 6-minute walk, exercise test, or Holter monitor once rate-controlling agents have been titrated.⁷

When atrial fibrillation is first diagnosed, it may not be possible to determine if it is paroxysmal (ie, self-terminating) or persistent. If the episode does not quickly end on its own, consideration may be given to restoring sinus rhythm.

Although experts debate the merits of a rate control approach vs a rhythm control approach for managing atrial fibrillation in the long term, many, including ourselves, recommend trying to restore sinus rhythm at least once when atrial fibrillation is first discovered. It is not always clear if atrial fibrillation is truly asymptomatic. Symptoms such as fatigue or decreased exercise tolerance can be subtle. Additionally, these symptoms may be attributed to other factors such as deconditioning, obesity, or advancing age. Thus, in many cases, only restoring normal sinus rhythm for a time allows the patient and clinician to fully assess the symptoms attributable to atrial fibrillation.

Therefore, in patients with newly diagnosed atrial fibrillation, an attempt to restore sinus rhythm is often warranted. Exceptions are in select patients who have no apparent symptoms and who are very old or are deemed too frail to tolerate cardioversion.

Direct-current cardioversion is typically the treatment of choice when attempting to restore sinus rhythm. The procedure can be done without anticoagulation within 48 hours of the onset of atrial fibrillation, if the time of onset is clear.⁷ However, clinicians must be careful in defining the onset of atrial fibrillation for this purpose.

Symptoms such as fatigue or shortness of breath can be vague in terms of the exact time of onset and often cannot be relied upon for the purpose of deciding whether cardioversion can be done without anticoagulation. When in doubt, it is best to err on the side of safety and assume that the atrial fibrillation has been going on for more than 48 hours.

If the time of onset is unclear or if more than 48 hours have passed, there are two general strategies for proceeding to electrical cardioversion.

One is to order transesophageal echocardiography and begin anticoagulation therapy at the same time. If there is no thrombus in the left atrium, then cardioversion can be done.⁸ Therapeutic anticoagulation with heparin, low-molecular-weight heparin, or warfarin (Coumadin) should be achieved within 24 to 48 hours of transesophageal echocardiography and cardioversion to minimize the risk of thromboembolic events, which can occur even after sinus rhythm has been restored.

At our institution, we typically strive to achieve therapeutic anticoagulation with either heparin or low-molecular-weight heparin before cardioversion in this scenario so as to avoid situations in which a patient may undergo cardioversion but then fail to achieve therapeutic anticoagulation for some time due to unforeseen factors.

The other approach is to start warfarin and maintain a goal international normalized ratio (INR) of 2 to 3 for 3 weeks, at which time cardioversion can be performed safely without transesophageal echocardiography.⁸

Regardless of which strategy is used, anticoagulation should be continued for at least 4 weeks after cardioversion,⁸ as atrial dysfunction and the risk of stroke may persist for days to weeks after normal sinus rhythm is restored.⁹

Role of antiarrhythmic drugs

Antiarrhythmic drugs can be used for chemical cardioversion or, more often, to help maintain sinus rhythm after direct-current cardioversion.

Because most of these drugs have at least a small chance of restoring normal sinus rhythm, we need to follow the same rules when starting them as when performing direct-current cardioversion. Patients should not be started on an antiarrhythmic medication until they have had adequate anticoagulation for at least 3 weeks or adequate anticoagulation and a transesophageal echocardiogram confirming that there is no thrombus in the left atrium.

Antiarrhythmic drugs should be started in select patients with newly diagnosed atrial fibrillation in whom a rhythm control strategy will be pursued. For patients whose history suggests a single episode, or episodes that previously self-terminated, an antiarrhythmic may not be necessary. For those with frequent episodes or whose history suggests ongoing atrial fibrillation for a long period, an antiarrhythmic will likely be required to provide a reasonable chance of achieving freedom from atrial fibrillation.

The choice of antiarrhythmic drug should be tailored to the specific patient.

Propafenone (Rythmol) and flecainide (Tambocor) are first-line drugs⁷ but are contraindicated in patients with coronary artery disease and significant structural heart disease.¹⁰

Sotalol (Betapace) and dofetilide (Tikosyn) can be used in patients with coronary artery disease. However, sotalol is contraindicated in patients with congestive heart failure, and dofetilide carries a long list of drug interactions. Both must be used with extreme caution in patients with renal insufficiency, and hospital admission is required for initiation or upward titration of the dose.

Amiodarone (Cordarone) is effective, and in the short term it is typically very well tolerated. However, it has a long half-life, and its potential for long-term toxicity often makes it a poor choice for long-term treatment. The toxicity of amiodarone increases with the cumulative dose. Therefore, this drug should be avoided for long-term therapy of atrial fibrillation in younger patients.

The ‘pill-in-the-pocket’ strategy

The “pill-in-the-pocket” strategy, in which patients are instructed to take their medication only when they have a bout of atrial fibrillation, is a reasonable option for patients with symptomatic recurrences of paroxysmal atrial fibrillation. This strategy is mainly reserved for patients who have relatively infrequent recurrences. Those who have frequent recurrences are usually more effectively treated with daily dosing of an antiarrhythmic. Flecainide and propafenone are the agents of choice for this approach because of their safety profile and efficacy in chemical cardioversion.

While this strategy may be started on an outpatient basis in patients with lone, paroxysmal atrial fibrillation, those with structural heart disease or conduction abnormalities should be observed in the hospital during initiation of therapy to observe for excessive PR prolongation or development of dangerous or worrisome arrhythmias.^11–13

Additionally, these agents can decrease the refractory period of the atrioventricular node, thereby increasing the ventricular rate. In the case of atrial flutter, patients may be converted from variable or 2:1 response to a 1:1 conduction. Thus, one should consider also using a beta-blocker with this strategy.

Since the goal of this approach is to convert the patient to sinus rhythm within a few hours of the onset of atrial fibrillation, it may be implemented without the use of warfarin. Patients are instructed that if they do not convert to normal sinus rhythm within a few hours, they should notify the physician so they can undergo electrical cardioversion within the 48-hour window from the onset of atrial fibrillation.

Dronedarone, a new antiarrhythmic drug

Dronedarone (Multaq) is now available and has been shown to be effective in treating atrial fibrillation.¹⁴ It has a long half-life and a mechanism of action similar to that of amiodarone. However, it may be inferior to amiodarone in terms of efficacy.¹⁵ It is metabolized by CYP3A4. No dosage adjustment is needed for patients with renal insufficiency.

Because dronedarone lacks the iodine moiety found in amiodarone, it should not carry the same toxicity profile. No pulmonary or thyroid toxicity was reported in early trials.¹⁶

Nevertheless, dronedarone has several important limitations. It carries a black box warning stating it is contraindicated in patients with severe or recently decompensated heart failure, as the mortality rate was twice as high when this drug was used in such patients in initial studies.¹⁷ Additionally, there have been reports of hepatotoxicity requiring liver transplantation in a small number of patients. The extent of this problem and strategies for avoiding it are not yet defined as of the writing of this paper. As with any new medication, patients who are started on dronedarone should be observed closely for any side effects, and these should be reported to assist in the development of the drug’s safety profile.

In a procedure that can potentially cure atrial fibrillation, catheters are inserted into the left atrium and rings of scar tissue are created around the ostia of the pulmonary veins using radiofrequency energy, electrically isolating them from the rest of the left atrium.

Some debate exists as to whether this procedure may be reasonable as a first-line therapy for some patients with atrial fibrillation.^18,19 It may be considered as an early treatment strategy in a small subset of patients, specifically young patients with symptomatic, recurrent atrial fibrillation, especially if they are averse to long-term antiarrhythmic therapy.

Because patients may still be more prone to atrial arrhythmias for several weeks to months after the procedure, they must be able to tolerate anticoagulation with warfarin for at least several months.

Rate control vs rhythm control

The choice between a rate control strategy or a rhythm control strategy in the long term is not always straightforward. While atrial fibrillation is clearly associated with higher morbidity and mortality rates, there are few data to date showing that restoring and maintaining sinus rhythm in patients with atrial fibrillation reduce the incidence of morbid complications or the likelihood of death.

Thus, current guidelines recommend a rate control strategy in patients who have no symptoms, and a rhythm control strategy if rate control cannot be achieved or if symptoms persist despite adequate control of the heart rate.⁷ The circumstances and preferences of the individual patient should carry weight in this decision.

Trials are under way that may shed more light on the relative benefits of rhythm control with ablation or antiarrhythmics and rate control.

PREVENTING THROMBOEMBOLIC EVENTS

Warfarin

In the short term, warfarin therapy may be dictated by plans to restore sinus rhythm. Patients need warfarin for at least 4 weeks after cardioversion unless it is performed within 48 hours of the onset of atrial fibrillation.

The CHADS₂score (1 point each for congestive heart failure, hypertension, age 75 or older, and diabetes mellitus; 2 points for prior stroke or transient ischemic attack) is useful when deciding whether to give long-term anticoagulation.

For patients with a score of 0, the risk of stroke is lower than the risk of a major bleeding complication while on therapeutic warfarin.^20,21 For these patients, aspirin 81 to 325 mg daily is recommended for stroke prophylaxis.

For those with a score of 2 or greater, the risk of stroke without warfarin is greater than the risk of a major bleeding complication with warfarin. These patients should receive warfarin with a goal INR of 2.0 to 3.0.⁷

Patients with a CHADS₂ score of 1 present a dilemma, as their risk of stroke without warfarin is about the same as their risk of a major bleeding complication with warfarin. They can be managed with either warfarin or aspirin, according to the physician’s judgment.⁷ In these cases, factors such as hobbies or professions that might increase the risk of bleeding, perceived frequency of atrial fibrillation episodes, and even patient preconceptions about warfarin are often used when deciding between aspirin and warfarin.

Patients with a CHADS₂ score of 2 or greater with a single episode of atrial fibrillation and a likely reversible cause may also pose a dilemma when deciding whether to start warfarin. These patients have demonstrated they at least have the substrate to maintain atrial fibrillation. This situation again calls for physician judgment. Bear in mind that asymptomatic recurrences are common in patients with atrial fibrillation.^22,23 A higher CHADS₂ score denotes a greater risk of stroke and may influence this decision. It is usually beneficial to enlist the patient in this decision-making process, as patients often have very strong opinions about tolerance of the risk of stroke or of warfarin therapy itself.

Another strategy is to start anticoagulation with warfarin and aggressively monitor for recurrences. If the patient has no recurrences of atrial fibrillation after 6 to 12 months and the reversible cause is resolved, one can then revisit the need for warfarin.

Role of aspirin and clopidogrel

Aspirin, alone or in conjunction with clopidogrel (Plavix), may provide an alternative for stroke prophylaxis in patients in whom warfarin is contraindicated. While inferior to warfarin, the combination of aspirin and clopidogrel has been shown to decrease the incidence of major thromboembolic events, especially stroke.²⁴ However, the risk of a major bleeding complication was also significantly increased.

This combination may be a reasonable strategy in select patients with a CHADS₂ score of 2 or greater in whom warfarin cannot be used for reasons such as personal aversion to the medication, side effects, or nonbleeding complications or in patients whose INR is exceedingly difficult to keep within the therapeutic range.

Dabigatran, a new anticoagulant

The newest option for anticoagulation in patients with atrial fibrillation is a direct thrombin inhibitor, dabigatran (Pradaxa).

In the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial,²⁵ dabigatran was studied head-to-head with warfarin. The doses of dabigatran studied were 110 mg and 150 mg twice a day. At 150 mg twice a day, patients on dabigatran had a lower rate of stroke than with warfarin (1.11% vs 1.69%, P < .001), as well as a lower rate of central nervous system bleeding (0.10% vs 0.38% with warfarin, P < .001). The rates of major bleeding were comparable in the patients receiving warfarin or dabigatran 150 mg twice a day, but the rate of gastrointestinal bleeding was higher in the dabigatran group (1.51% vs 1.02% with warfarin, P < .001).²⁵

Dabigatran was recently approved by the US Food and Drug Administration for use in patients with atrial fibrillation. Doses of 150 mg and 75 mg are available.

Dabigatran is renally excreted, and the 150 mg twice-a-day dosing is intended for patients with a creatinine clearance greater than 30 mL/min. The 75-mg twice-a-day dosing is intended for patients with a creatinine clearance of 15 to 30 mL/min. However, it should be noted that currently there are no data to support the 75-mg twice-a-day dosing.

Dabigatran does have several advantages over warfarin. Patients do not need to avoid foods containing vitamin K, and routine serial monitoring does not appear to be needed. As with any new medication, patients who are started on dabigatran should be observed closely for any side effects, and these should be reported to assist in the development of the drug’s safety profile.

SPECIAL CIRCUMSTANCES

After cardiac or noncardiac surgery

Atrial fibrillation is common after open heart surgery, occurring in approximately 25% to 50% of patients.^26–28

When this happens, at least one or two attempts are made to restore sinus rhythm. Especially in the early postoperative period, anticoagulation with heparin or warfarin may be contraindicated, so careful attention must be paid to the patient’s heart rhythm so that atrial fibrillation can be recognized quickly and cardioversion performed within a 48-hour window of onset. Beta-blockers, diltiazem, and verapamil are typically used for rate control.

When atrial fibrillation recurs in patients who have undergone open heart surgery, antiarrhythmics are started early to help prevent further recurrences. At our institution, we usually use amiodarone, as it is highly effective and well tolerated in the short term. When started on amiodarone for postoperative atrial fibrillation, patients are informed that the drug will be stopped after about 2 to 3 months. For patients who continue to have bouts of atrial fibrillation, the need for antiarrhythmic medications can be reassessed, and, if needed, the optimal antiarrhythmic medication for long-term therapy for the patient can be chosen.

Atrial fibrillation in severe, acute illness

Atrial fibrillation is common in the setting of extreme systemic stressors such as shock and sepsis and when the patient is being supported with inotropic agents. In this setting, patients may be in a high-catecholamine state, and both the heart rate and the heart rhythm may be very difficult to control.

Beta-blockers and nondihydropyridine calcium channel blockers should not be used when patients are on medications to support blood pressure, and in this setting, when the patient’s hemodynamic status permits the use of these agents, their effect may be minimal.

Amiodarone or perhaps digoxin may slow the heart rate somewhat without too much effect on the blood pressure. However, with amiodarone, one may have to accept a risk of chemical cardioversion.

Electrical cardioversion with or without the assistance of an antiarrhythmic drug may control the heart rate by restoring sinus rhythm. However, atrial fibrillation often recurs, and if it recurs quickly one may have to accept elevated heart rates until the underlying process is addressed.

PALM BEACH, FLA. - Many patients with chronic mesenteric vascular insufficiency can be treated with an endovascular approach - either angioplasty or stenting with bare metal or covered devices.

Unlike open procedures, the endovascular approach carries a low risk of postoperative morbidity and mortality, Dr. Phillip Burns said at the annual meeting of the Southern Surgical Association. However, he noted, the recurrence rate for stenosis or occlusion was high in his retrospective series, with about one-third of patients requiring a second, or even third, intervention within the first 2 years after surgery.

Thus, an intensive follow-up is necessary for patients who undergo endovascular reconstruction. Under his protocol, patients return every 6 months for a clinical exam and duplex ultrasound, said Dr. Burns of the University of Tennessee, Chattanooga.

"Secondary procedures are often indicated for recurrent stenosis, and you have to look for this carefully," he said. Signs and symptoms might not be observed initially, "but if you continue to search for them, you will find them and be able to perform the reinterventions."

Dr. Burns and his colleagues presented a retrospective study of 107 patients with 127 vessels treated from 2004 to June 2010. All of the procedures were performed by a vascular specialist in an endovascular operating suite.

Patients were usually referred for gastrointestinal symptoms and already had undergone a GI workup. Most (88%) complained of abdominal pain; 55% had experienced weight loss and 29% reported nausea. All underwent an abdominal ultrasound that showed mesenteric vascular abnormalities.

The patients' average age was 59 years (range 18-90 years). Most (70%) were women. As a group, they displayed several important comorbidities, including hypertension, diabetes, coronary artery disease, and smoking.

Of the 127 vessels treated, 68 were superior mesenteric arteries, 52 were celiac arteries, and 7 were inferior mesenteric arteries. A balloon-expandable bare metal stent was most commonly used (66%; 87 patients) followed by balloon angioplasty (22%; 29), covered stent (10%; 14), and one self-expanding stent (1%; 1). All patients were put on either aspirin or clopidogrel therapy for at least 30 days after surgery. Patients also received continuing treatment for the hyperlipidemia that caused their atherosclerotic disease.

At 1 year, primary patency was seen in 67% of those with angioplasty, 54% of those with bare metal stents, and 100% of those with covered stents. The patency rates for the two stent types were significantly different.

More than half of the patients (57%; 55) experienced complete resolution of their symptoms, but 38% of these (21) required a second intervention. Of the 43% (41) who reported partial symptom relief, more than half (59%; 24) required a reintervention.

"That led to 45 patients going back for at least one other intervention," Dr. Burns said. "Five were not deemed treatable endovascularly and were done as open procedures. All others were done endovascularly, with 25 requiring a second reintervention and 8, a third reintervention."

In the reinterventions, 1-year patency was 86% with angioplasty, 97% with bare metal stents, and 100% with covered stents. There were 11 deaths in the cohort, 2 of which were due to chronic mesenteric vascular disease.

"In our opinion, both of those were in patients who did not follow up appropriately," said Dr. Christopher J. LeSar, also of the University of Tennessee, who closed the paper. "It's our belief that in treating this disease, the endovascular approach is reasonable if it's married to a very stringent follow-up protocol. Patients were counseled to be very wary of any recurrent symptoms and to act on them immediately if they occurred."

During the discussion, Dr. Eugene M. Langan III "facs" of the Greenville (S.C.) Hospital System University Medical Center, asked if the good outcomes associated with the covered stent are enough to recommend its use as the primary reconstruction method.

It's too early to make the assumption, said Dr. LeSar. The covered stents were only used in only 25 patients with an average follow-up of just 6 months. "This was related to the fact that we discovered [the covered stent success] later in our clinical experience," said Dr. LeSar. "In this population, one of the main problems was recurrent disease, and we found that only four patients with a covered stent required additional reinterventions, which led us to consider placing this type of stent as the primary answer for prevention of stenosis."

The crux of the issue is how to predict who can reap the biggest benefit from endovascular repair, leaving open surgery only to those who really require it, said Dr. Marc Mitchell of the University of Mississippi, Jackson. That seems to remain an unknown, said Dr. LeSar.

"We don't know why many develop hyperplasia, but some tend to and it seems to be random," he said.

Neither Dr. Burns nor Dr. LeSar reported any financial conflicts.

PALM BEACH, FLA. - Many patients with chronic mesenteric vascular insufficiency can be treated with an endovascular approach - either angioplasty or stenting with bare metal or covered devices.

Unlike open procedures, the endovascular approach carries a low risk of postoperative morbidity and mortality, Dr. Phillip Burns said at the annual meeting of the Southern Surgical Association. However, he noted, the recurrence rate for stenosis or occlusion was high in his retrospective series, with about one-third of patients requiring a second, or even third, intervention within the first 2 years after surgery.

Thus, an intensive follow-up is necessary for patients who undergo endovascular reconstruction. Under his protocol, patients return every 6 months for a clinical exam and duplex ultrasound, said Dr. Burns of the University of Tennessee, Chattanooga.

"Secondary procedures are often indicated for recurrent stenosis, and you have to look for this carefully," he said. Signs and symptoms might not be observed initially, "but if you continue to search for them, you will find them and be able to perform the reinterventions."

Dr. Burns and his colleagues presented a retrospective study of 107 patients with 127 vessels treated from 2004 to June 2010. All of the procedures were performed by a vascular specialist in an endovascular operating suite.

Patients were usually referred for gastrointestinal symptoms and already had undergone a GI workup. Most (88%) complained of abdominal pain; 55% had experienced weight loss and 29% reported nausea. All underwent an abdominal ultrasound that showed mesenteric vascular abnormalities.

The patients' average age was 59 years (range 18-90 years). Most (70%) were women. As a group, they displayed several important comorbidities, including hypertension, diabetes, coronary artery disease, and smoking.

Of the 127 vessels treated, 68 were superior mesenteric arteries, 52 were celiac arteries, and 7 were inferior mesenteric arteries. A balloon-expandable bare metal stent was most commonly used (66%; 87 patients) followed by balloon angioplasty (22%; 29), covered stent (10%; 14), and one self-expanding stent (1%; 1). All patients were put on either aspirin or clopidogrel therapy for at least 30 days after surgery. Patients also received continuing treatment for the hyperlipidemia that caused their atherosclerotic disease.

At 1 year, primary patency was seen in 67% of those with angioplasty, 54% of those with bare metal stents, and 100% of those with covered stents. The patency rates for the two stent types were significantly different.

More than half of the patients (57%; 55) experienced complete resolution of their symptoms, but 38% of these (21) required a second intervention. Of the 43% (41) who reported partial symptom relief, more than half (59%; 24) required a reintervention.

"That led to 45 patients going back for at least one other intervention," Dr. Burns said. "Five were not deemed treatable endovascularly and were done as open procedures. All others were done endovascularly, with 25 requiring a second reintervention and 8, a third reintervention."

In the reinterventions, 1-year patency was 86% with angioplasty, 97% with bare metal stents, and 100% with covered stents. There were 11 deaths in the cohort, 2 of which were due to chronic mesenteric vascular disease.

"In our opinion, both of those were in patients who did not follow up appropriately," said Dr. Christopher J. LeSar, also of the University of Tennessee, who closed the paper. "It's our belief that in treating this disease, the endovascular approach is reasonable if it's married to a very stringent follow-up protocol. Patients were counseled to be very wary of any recurrent symptoms and to act on them immediately if they occurred."

During the discussion, Dr. Eugene M. Langan III "facs" of the Greenville (S.C.) Hospital System University Medical Center, asked if the good outcomes associated with the covered stent are enough to recommend its use as the primary reconstruction method.

It's too early to make the assumption, said Dr. LeSar. The covered stents were only used in only 25 patients with an average follow-up of just 6 months. "This was related to the fact that we discovered [the covered stent success] later in our clinical experience," said Dr. LeSar. "In this population, one of the main problems was recurrent disease, and we found that only four patients with a covered stent required additional reinterventions, which led us to consider placing this type of stent as the primary answer for prevention of stenosis."

The crux of the issue is how to predict who can reap the biggest benefit from endovascular repair, leaving open surgery only to those who really require it, said Dr. Marc Mitchell of the University of Mississippi, Jackson. That seems to remain an unknown, said Dr. LeSar.

"We don't know why many develop hyperplasia, but some tend to and it seems to be random," he said.

Neither Dr. Burns nor Dr. LeSar reported any financial conflicts.

PALM BEACH, FLA. - Many patients with chronic mesenteric vascular insufficiency can be treated with an endovascular approach - either angioplasty or stenting with bare metal or covered devices.

Unlike open procedures, the endovascular approach carries a low risk of postoperative morbidity and mortality, Dr. Phillip Burns said at the annual meeting of the Southern Surgical Association. However, he noted, the recurrence rate for stenosis or occlusion was high in his retrospective series, with about one-third of patients requiring a second, or even third, intervention within the first 2 years after surgery.

Thus, an intensive follow-up is necessary for patients who undergo endovascular reconstruction. Under his protocol, patients return every 6 months for a clinical exam and duplex ultrasound, said Dr. Burns of the University of Tennessee, Chattanooga.

"Secondary procedures are often indicated for recurrent stenosis, and you have to look for this carefully," he said. Signs and symptoms might not be observed initially, "but if you continue to search for them, you will find them and be able to perform the reinterventions."

Dr. Burns and his colleagues presented a retrospective study of 107 patients with 127 vessels treated from 2004 to June 2010. All of the procedures were performed by a vascular specialist in an endovascular operating suite.

Patients were usually referred for gastrointestinal symptoms and already had undergone a GI workup. Most (88%) complained of abdominal pain; 55% had experienced weight loss and 29% reported nausea. All underwent an abdominal ultrasound that showed mesenteric vascular abnormalities.

The patients' average age was 59 years (range 18-90 years). Most (70%) were women. As a group, they displayed several important comorbidities, including hypertension, diabetes, coronary artery disease, and smoking.

Of the 127 vessels treated, 68 were superior mesenteric arteries, 52 were celiac arteries, and 7 were inferior mesenteric arteries. A balloon-expandable bare metal stent was most commonly used (66%; 87 patients) followed by balloon angioplasty (22%; 29), covered stent (10%; 14), and one self-expanding stent (1%; 1). All patients were put on either aspirin or clopidogrel therapy for at least 30 days after surgery. Patients also received continuing treatment for the hyperlipidemia that caused their atherosclerotic disease.

At 1 year, primary patency was seen in 67% of those with angioplasty, 54% of those with bare metal stents, and 100% of those with covered stents. The patency rates for the two stent types were significantly different.

More than half of the patients (57%; 55) experienced complete resolution of their symptoms, but 38% of these (21) required a second intervention. Of the 43% (41) who reported partial symptom relief, more than half (59%; 24) required a reintervention.

"That led to 45 patients going back for at least one other intervention," Dr. Burns said. "Five were not deemed treatable endovascularly and were done as open procedures. All others were done endovascularly, with 25 requiring a second reintervention and 8, a third reintervention."

In the reinterventions, 1-year patency was 86% with angioplasty, 97% with bare metal stents, and 100% with covered stents. There were 11 deaths in the cohort, 2 of which were due to chronic mesenteric vascular disease.

"In our opinion, both of those were in patients who did not follow up appropriately," said Dr. Christopher J. LeSar, also of the University of Tennessee, who closed the paper. "It's our belief that in treating this disease, the endovascular approach is reasonable if it's married to a very stringent follow-up protocol. Patients were counseled to be very wary of any recurrent symptoms and to act on them immediately if they occurred."

During the discussion, Dr. Eugene M. Langan III "facs" of the Greenville (S.C.) Hospital System University Medical Center, asked if the good outcomes associated with the covered stent are enough to recommend its use as the primary reconstruction method.

It's too early to make the assumption, said Dr. LeSar. The covered stents were only used in only 25 patients with an average follow-up of just 6 months. "This was related to the fact that we discovered [the covered stent success] later in our clinical experience," said Dr. LeSar. "In this population, one of the main problems was recurrent disease, and we found that only four patients with a covered stent required additional reinterventions, which led us to consider placing this type of stent as the primary answer for prevention of stenosis."

The crux of the issue is how to predict who can reap the biggest benefit from endovascular repair, leaving open surgery only to those who really require it, said Dr. Marc Mitchell of the University of Mississippi, Jackson. That seems to remain an unknown, said Dr. LeSar.

"We don't know why many develop hyperplasia, but some tend to and it seems to be random," he said.

Neither Dr. Burns nor Dr. LeSar reported any financial conflicts.

A 54-year-old African-American man was brought by police officers to the emergency department (ED) after he called 911 several times to report seeing a Rottweiler looking into his second-story window. At the scene, the police were unable to confirm his story, thought the man seemed intoxicated, and brought him to the ED for evaluation.

The patient reported that he had been drinking the previous evening but denied current intoxication or illicit drug use. He denied experiencing symptoms of alcohol withdrawal.

Regarding his medical history, the patient admitted to having had seizures, including two episodes that he said required hospitalization. He described these episodes as right-hand “tingling” (paresthesias), accompanied by right-facial numbness and aphasia. The patient said his physician had instructed him to take “a few phenytoin pills” whenever these episodes occurred. He reported that the medication usually helped resolve his symptoms. He said he had taken phenytoin shortly before his current presentation.

According to friends of the patient who were questioned, he had had noticeable memory problems during the previous six to eight months. They said that he often told the same joke, day after day. His speech had become increasingly slurred, even when he was not drinking.

Once the patient’s medical records were retrieved, it was revealed that he had been hospitalized twice for witnessed grand mal seizures about six months before his current admission; he had been drinking alcohol prior to both episodes. He underwent electroencephalography (EEG) during one of these hospitalizations, with results reported as normal. On both occasions, the patient was discharged with phenytoin and was instructed to follow up with his primary care provider and neurologist.

The patient, who reported working in customer service, had no known allergies. He claimed to drink one or two 40-ounce beers twice per week and admitted to occasional cocaine use. Of significance in his family history was a fatal MI in his mother. Although the patient denied any history of rashes or lesions, his current delirium made it impossible to obtain a reliable sexual history; a friend who was questioned, however, described the patient as promiscuous.

On initial physical examination, the man was afebrile, tachycardic, and somewhat combative with the ED staff. He was fully oriented to self but only partially to place and time.

His right pupil was 3+ and his left pupil was 2+, with neither reactive to light. He spoke with tangential speech and his gait was unsteady, but no other significant abnormalities were noted. A full assessment revealed no rashes or other lesions.

Significant laboratory findings included a low level of phenytoin, a negative blood alcohol level, presence of cocaine on urine drug screening, and normal levels of thyroid-stimulating hormone (TSH), vitamin B12, and folate. The patient’s serum VDRL (venereal disease research laboratory) titer was positive at 1:256.

Electroencephalography showed diffuse slowing, and brain CT performed in the ED showed atrophy that was mild but appropriate for a person of the patient’s age, with no evidence of a cerebrovascular accident (CVA). Aneurysm was ruled out by CT angiography of the brain. MRI revealed persistent increased signal in the subarachnoid space.

The patient was admitted with an initial diagnosis of paranoid delusional psychosis and monitored for alcohol withdrawal. He was given lorazepam as needed for agitation. Consultations were arranged with the psychiatry service regarding his delusions, and with neurology to determine whether to continue phenytoin.

The patient showed little response during the next several days. Based on positive results on serum VDRL with high titer, the presence of Argyll-Robertson pupils on exam, and his history of dementia-like symptoms, a lumbar puncture was performed to rule out neurosyphilis. In the patient’s cerebral spinal fluid (CSF) analysis, the first tube was clear and colorless, with 72 cells (28% neutrophils, 59% lymphocytes); glucose, 64 mg/dL; and total protein, 117 mg/dL. The fourth tube had 34 cells (17% neutrophils, 65% lymphocytes) and a positive VDRL titer at 1:128. Results from a serum syphilis immunoglobulin G (IgG) test were positive, and HIV antibody testing was nonreactive, confirming the diagnosis of neurosyphilis.

The hospital’s infectious disease (ID) team recommended treatment with IV penicillin for 14 days. Once this was completed, the patient was discharged with instructions to follow up at the ID clinic in three months for a repeat CSF VDRL titer to monitor for resolution of the disease. His prescription for phenytoin was discontinued.

At the time of discharge, it was noted that the patient showed no evidence of having regained cognitive function. He was deemed by the psychiatry service to lack decision-making capacity—a likely sequelae of untreated neurosyphilis of unknown duration.

He did return to the ID clinic six months after his discharge. At that visit, a VDRL serum titer was drawn with a result of 1:64, a decrease from 1:128. His syphilis IgG remained positive, however.

Discussion
Definition and Epidemiology
Syphilis is commonly known as a sexually transmitted disease with primary, secondary, and tertiary (early and late latent) stages.¹ Neurosyphilis is defined as a manifestation of the inflammatory response to invasion over decades by the Treponema pallidum spirochete in the CSF as a result of untreated primary and/or secondary syphilis.² About one in 10 patients with untreated syphilis will experience neurologic involvement.^3,4 Before 2005, neurosyphilis was required to be reported as a specific stage of syphilis (ie, a manifestation of tertiary syphilis4), but now should be reported as syphilis with neurologic manifestations.⁵

A reportable infectious disease, syphilis was widespread until the advent of penicillin. According to CDC statistics,⁶ the number of reported cases of primary and secondary syphilis has declined steadily since 1943. In the late 1970s and early 1980s, the number of tertiary cases also began to plateau, likely as a result of earlier diagnosis and more widespread use of penicillin. Recent case reports suggest greater prevalence of syphilis among men than women and increased incidence among men who have sex with men.⁷

Pathogenesis
Syphilis is most commonly spread by sexual contact or contact with an infected primary lesion (chancre). Less likely routes of transmission are placental passage or blood transfusion. Infectivity is greatest in the early disease stages.⁸

Primary syphilis is marked by transmission of the spirochete, ending with development of secondary syphilis (usually two to 12 weeks after transmission). A chancre commonly develops but is often missed by patients because it is painless and can heal spontaneously.⁷ The chancre is also often confused with two other sources of genital lesions, herpes simplex (genital herpes) and Haemophilus ducreyi (chancroid). In two-thirds of cases of untreated primary syphilis, the infection clears spontaneously, but in the remaining one-third, the disease progresses.⁸

Secondary syphilis, with or without presence of a chancre, manifests with constitutional symptoms, including lymphadenopathy, fever, headache, and malaise. Patients in this disease phase may also present with a generalized, nonpruritic, macular to maculopapular or pustular rash. The rash can affect the skin of the trunk, the proximal extremities, and the palms and soles. Ocular involvement may occur, especially in patients who are coinfected with HIV.⁸ In either primary or secondary syphilis, infection can invade the central nervous system.¹

During latent syphilis, patients show serologic conversion without overt symptoms. Early latent syphilis is defined as infection within the previous year, as demonstrated by conversion from negative to positive testing, or an increase in titers within the previous year. Any case occurring after one year is defined as late or unknown latent syphilis.⁸

Tertiary syphilis is marked by complications resulting from untreated syphilis; affected patients commonly experience central nervous system and cardiovascular involvement. Gummatous disease is seen in 15% of patients.¹

The early stages of neurosyphilis may be asymptomatic, acute meningeal, and meningovascular.^1,4,8,9 Only 5% of patients with early neurosyphilis are symptomatic, with the added potential for cranial neuritis or ocular involvement.¹ The late stages of neurosyphilis are detailed in the table.^1,4,8

Diagnosis
A diagnosis of syphilis is made by testing blood samples or scrapings from a lesion. In patients with suspected syphilis, rapid plasma reagin (RPR) testing or a VDRL titer is commonly ordered. When results are positive, a serum treponemal test is recommended to confirm a diagnosis of syphilis. Options include the fluorescent treponemal antibody absorption test (FTA-ABS) and the microhemagglutinin assay for antibody to T pallidum (MHA-TP).⁵

If neurologic symptoms are present, a CSF sample should be obtained, followed by the same testing. A confirmed diagnosis of neurosyphilis is defined by the CDC as syphilis at any stage that meets laboratory criteria for neurosyphilis⁵; these include increased CSF protein or an elevated CSF leukocyte count with no other known cause, and clinical signs or symptoms without other known causes.⁷

Treatment
Treatment of syphilis generally consists of penicillin, administered intramuscularly (IM) or IV, depending on the stage. According to 2006 guidelines from the CDC,^10,11 treatment for adults with primary and secondary syphilis is a single dose of IM penicillin G, 2.4 million units. If neurosyphilis is suspected, recommended treatment is IV penicillin G, 18 to 24 million units per day divided into six doses (ie, 3 to 4 million units every four hours) or continuous pump infusion for 10 to 14 days.^10-12 Follow-up is recommended by monitoring CSF titers to ensure clearance of infection; retreatment may be required if CSF abnormalities persist after two years.¹¹

Patients with a penicillin allergy should undergo desensitization, as penicillin is the preferred agent; the potential exists for cross-reactivity with ceftriaxone, a possible alternative for patients with neurosyphilis.¹¹ All patients diagnosed with syphilis should also be tested for HIV and other sexually transmitted diseases.^10-12

The prognosis of patients treated for neurosyphilis is generally good if the condition is diagnosed and treated early. In patients with cerebral atrophy, frontal lesions, dementia, or tabes dorsalis, the potential for recovery decreases.^2,13,14

Teaching Points
There are several teaching points to take away from this case:

• Remember to rule out a CVA in any patient who presents with numbness, paresthesias, or slurred speech. In this case, a brain CT and CT angiography of the brain were both obtained in the ED before the patient was admitted. They both yielded negative results; because the patient’s history was consistent with alcohol and drug use and he had a history of seizures, he was monitored closely for signs of withdrawal or further seizure.

• Phenytoin is an antiepileptic agent whose use requires proper patient education and drug level monitoring. Appropriate follow-up must be ensured before phenytoin therapy is begun, as toxicity can result in nystagmus, ataxia, slurred speech, decreased coordination, mental confusion, and possibly death.^15,16

• For patients with a suspected acute change in mental status, a workup is required and should be tailored appropriately, based on findings. This should include, but not be limited to, a thorough history and physical exam, CT of the brain (to rule out an acute brain injury¹⁷), and, if warranted, MRI of the brain. Also, a urine drug screen and alcohol level, a complete blood count, a TSH level (to evaluate for altered thyroid function that may explain mental status changes), comprehensive panel, RPR testing and/or a VDRL titer should be obtained, depending on the facility’s protocol^18,19; at some facilities, a treponemal test, rather than VDRL, is being obtained at the outset.²⁰ Levels of vitamin B12 (as part of the dementia workup), folate, thiamine, and ammonia (in patients with suspected liver disease) can also be obtained in patients with change in mental status.^18,19 Urinalysis should not be overlooked to check for a urinary tract infection, especially in elderly patients.²¹

• If primary syphilis is suspected, treatment must be undertaken.²⁰

Conclusion
Despite the decline seen since the 1940s in cases of primary and secondary syphilis, and the effectiveness of penicillin in treating the infection early, patients with late-stage syphilis, including those with neurosyphilis, may still present to the emergency care, urgent care, or primary care setting. Immediate treatment with penicillin is recommended to achieve an optimal prognosis for the affected patient.

A 54-year-old African-American man was brought by police officers to the emergency department (ED) after he called 911 several times to report seeing a Rottweiler looking into his second-story window. At the scene, the police were unable to confirm his story, thought the man seemed intoxicated, and brought him to the ED for evaluation.

The patient reported that he had been drinking the previous evening but denied current intoxication or illicit drug use. He denied experiencing symptoms of alcohol withdrawal.

Regarding his medical history, the patient admitted to having had seizures, including two episodes that he said required hospitalization. He described these episodes as right-hand “tingling” (paresthesias), accompanied by right-facial numbness and aphasia. The patient said his physician had instructed him to take “a few phenytoin pills” whenever these episodes occurred. He reported that the medication usually helped resolve his symptoms. He said he had taken phenytoin shortly before his current presentation.

According to friends of the patient who were questioned, he had had noticeable memory problems during the previous six to eight months. They said that he often told the same joke, day after day. His speech had become increasingly slurred, even when he was not drinking.

Once the patient’s medical records were retrieved, it was revealed that he had been hospitalized twice for witnessed grand mal seizures about six months before his current admission; he had been drinking alcohol prior to both episodes. He underwent electroencephalography (EEG) during one of these hospitalizations, with results reported as normal. On both occasions, the patient was discharged with phenytoin and was instructed to follow up with his primary care provider and neurologist.

The patient, who reported working in customer service, had no known allergies. He claimed to drink one or two 40-ounce beers twice per week and admitted to occasional cocaine use. Of significance in his family history was a fatal MI in his mother. Although the patient denied any history of rashes or lesions, his current delirium made it impossible to obtain a reliable sexual history; a friend who was questioned, however, described the patient as promiscuous.

On initial physical examination, the man was afebrile, tachycardic, and somewhat combative with the ED staff. He was fully oriented to self but only partially to place and time.

His right pupil was 3+ and his left pupil was 2+, with neither reactive to light. He spoke with tangential speech and his gait was unsteady, but no other significant abnormalities were noted. A full assessment revealed no rashes or other lesions.

Significant laboratory findings included a low level of phenytoin, a negative blood alcohol level, presence of cocaine on urine drug screening, and normal levels of thyroid-stimulating hormone (TSH), vitamin B12, and folate. The patient’s serum VDRL (venereal disease research laboratory) titer was positive at 1:256.

Electroencephalography showed diffuse slowing, and brain CT performed in the ED showed atrophy that was mild but appropriate for a person of the patient’s age, with no evidence of a cerebrovascular accident (CVA). Aneurysm was ruled out by CT angiography of the brain. MRI revealed persistent increased signal in the subarachnoid space.

The patient was admitted with an initial diagnosis of paranoid delusional psychosis and monitored for alcohol withdrawal. He was given lorazepam as needed for agitation. Consultations were arranged with the psychiatry service regarding his delusions, and with neurology to determine whether to continue phenytoin.

The patient showed little response during the next several days. Based on positive results on serum VDRL with high titer, the presence of Argyll-Robertson pupils on exam, and his history of dementia-like symptoms, a lumbar puncture was performed to rule out neurosyphilis. In the patient’s cerebral spinal fluid (CSF) analysis, the first tube was clear and colorless, with 72 cells (28% neutrophils, 59% lymphocytes); glucose, 64 mg/dL; and total protein, 117 mg/dL. The fourth tube had 34 cells (17% neutrophils, 65% lymphocytes) and a positive VDRL titer at 1:128. Results from a serum syphilis immunoglobulin G (IgG) test were positive, and HIV antibody testing was nonreactive, confirming the diagnosis of neurosyphilis.

The hospital’s infectious disease (ID) team recommended treatment with IV penicillin for 14 days. Once this was completed, the patient was discharged with instructions to follow up at the ID clinic in three months for a repeat CSF VDRL titer to monitor for resolution of the disease. His prescription for phenytoin was discontinued.

At the time of discharge, it was noted that the patient showed no evidence of having regained cognitive function. He was deemed by the psychiatry service to lack decision-making capacity—a likely sequelae of untreated neurosyphilis of unknown duration.

He did return to the ID clinic six months after his discharge. At that visit, a VDRL serum titer was drawn with a result of 1:64, a decrease from 1:128. His syphilis IgG remained positive, however.

Discussion
Definition and Epidemiology
Syphilis is commonly known as a sexually transmitted disease with primary, secondary, and tertiary (early and late latent) stages.¹ Neurosyphilis is defined as a manifestation of the inflammatory response to invasion over decades by the Treponema pallidum spirochete in the CSF as a result of untreated primary and/or secondary syphilis.² About one in 10 patients with untreated syphilis will experience neurologic involvement.^3,4 Before 2005, neurosyphilis was required to be reported as a specific stage of syphilis (ie, a manifestation of tertiary syphilis4), but now should be reported as syphilis with neurologic manifestations.⁵

A reportable infectious disease, syphilis was widespread until the advent of penicillin. According to CDC statistics,⁶ the number of reported cases of primary and secondary syphilis has declined steadily since 1943. In the late 1970s and early 1980s, the number of tertiary cases also began to plateau, likely as a result of earlier diagnosis and more widespread use of penicillin. Recent case reports suggest greater prevalence of syphilis among men than women and increased incidence among men who have sex with men.⁷

Pathogenesis
Syphilis is most commonly spread by sexual contact or contact with an infected primary lesion (chancre). Less likely routes of transmission are placental passage or blood transfusion. Infectivity is greatest in the early disease stages.⁸

Primary syphilis is marked by transmission of the spirochete, ending with development of secondary syphilis (usually two to 12 weeks after transmission). A chancre commonly develops but is often missed by patients because it is painless and can heal spontaneously.⁷ The chancre is also often confused with two other sources of genital lesions, herpes simplex (genital herpes) and Haemophilus ducreyi (chancroid). In two-thirds of cases of untreated primary syphilis, the infection clears spontaneously, but in the remaining one-third, the disease progresses.⁸

Secondary syphilis, with or without presence of a chancre, manifests with constitutional symptoms, including lymphadenopathy, fever, headache, and malaise. Patients in this disease phase may also present with a generalized, nonpruritic, macular to maculopapular or pustular rash. The rash can affect the skin of the trunk, the proximal extremities, and the palms and soles. Ocular involvement may occur, especially in patients who are coinfected with HIV.⁸ In either primary or secondary syphilis, infection can invade the central nervous system.¹

During latent syphilis, patients show serologic conversion without overt symptoms. Early latent syphilis is defined as infection within the previous year, as demonstrated by conversion from negative to positive testing, or an increase in titers within the previous year. Any case occurring after one year is defined as late or unknown latent syphilis.⁸

Tertiary syphilis is marked by complications resulting from untreated syphilis; affected patients commonly experience central nervous system and cardiovascular involvement. Gummatous disease is seen in 15% of patients.¹

The early stages of neurosyphilis may be asymptomatic, acute meningeal, and meningovascular.^1,4,8,9 Only 5% of patients with early neurosyphilis are symptomatic, with the added potential for cranial neuritis or ocular involvement.¹ The late stages of neurosyphilis are detailed in the table.^1,4,8

Diagnosis
A diagnosis of syphilis is made by testing blood samples or scrapings from a lesion. In patients with suspected syphilis, rapid plasma reagin (RPR) testing or a VDRL titer is commonly ordered. When results are positive, a serum treponemal test is recommended to confirm a diagnosis of syphilis. Options include the fluorescent treponemal antibody absorption test (FTA-ABS) and the microhemagglutinin assay for antibody to T pallidum (MHA-TP).⁵

If neurologic symptoms are present, a CSF sample should be obtained, followed by the same testing. A confirmed diagnosis of neurosyphilis is defined by the CDC as syphilis at any stage that meets laboratory criteria for neurosyphilis⁵; these include increased CSF protein or an elevated CSF leukocyte count with no other known cause, and clinical signs or symptoms without other known causes.⁷

Treatment
Treatment of syphilis generally consists of penicillin, administered intramuscularly (IM) or IV, depending on the stage. According to 2006 guidelines from the CDC,^10,11 treatment for adults with primary and secondary syphilis is a single dose of IM penicillin G, 2.4 million units. If neurosyphilis is suspected, recommended treatment is IV penicillin G, 18 to 24 million units per day divided into six doses (ie, 3 to 4 million units every four hours) or continuous pump infusion for 10 to 14 days.^10-12 Follow-up is recommended by monitoring CSF titers to ensure clearance of infection; retreatment may be required if CSF abnormalities persist after two years.¹¹

Patients with a penicillin allergy should undergo desensitization, as penicillin is the preferred agent; the potential exists for cross-reactivity with ceftriaxone, a possible alternative for patients with neurosyphilis.¹¹ All patients diagnosed with syphilis should also be tested for HIV and other sexually transmitted diseases.^10-12

The prognosis of patients treated for neurosyphilis is generally good if the condition is diagnosed and treated early. In patients with cerebral atrophy, frontal lesions, dementia, or tabes dorsalis, the potential for recovery decreases.^2,13,14

Teaching Points
There are several teaching points to take away from this case:

• Remember to rule out a CVA in any patient who presents with numbness, paresthesias, or slurred speech. In this case, a brain CT and CT angiography of the brain were both obtained in the ED before the patient was admitted. They both yielded negative results; because the patient’s history was consistent with alcohol and drug use and he had a history of seizures, he was monitored closely for signs of withdrawal or further seizure.

• Phenytoin is an antiepileptic agent whose use requires proper patient education and drug level monitoring. Appropriate follow-up must be ensured before phenytoin therapy is begun, as toxicity can result in nystagmus, ataxia, slurred speech, decreased coordination, mental confusion, and possibly death.^15,16

• For patients with a suspected acute change in mental status, a workup is required and should be tailored appropriately, based on findings. This should include, but not be limited to, a thorough history and physical exam, CT of the brain (to rule out an acute brain injury¹⁷), and, if warranted, MRI of the brain. Also, a urine drug screen and alcohol level, a complete blood count, a TSH level (to evaluate for altered thyroid function that may explain mental status changes), comprehensive panel, RPR testing and/or a VDRL titer should be obtained, depending on the facility’s protocol^18,19; at some facilities, a treponemal test, rather than VDRL, is being obtained at the outset.²⁰ Levels of vitamin B12 (as part of the dementia workup), folate, thiamine, and ammonia (in patients with suspected liver disease) can also be obtained in patients with change in mental status.^18,19 Urinalysis should not be overlooked to check for a urinary tract infection, especially in elderly patients.²¹

• If primary syphilis is suspected, treatment must be undertaken.²⁰

Conclusion
Despite the decline seen since the 1940s in cases of primary and secondary syphilis, and the effectiveness of penicillin in treating the infection early, patients with late-stage syphilis, including those with neurosyphilis, may still present to the emergency care, urgent care, or primary care setting. Immediate treatment with penicillin is recommended to achieve an optimal prognosis for the affected patient.

A 54-year-old African-American man was brought by police officers to the emergency department (ED) after he called 911 several times to report seeing a Rottweiler looking into his second-story window. At the scene, the police were unable to confirm his story, thought the man seemed intoxicated, and brought him to the ED for evaluation.

The patient reported that he had been drinking the previous evening but denied current intoxication or illicit drug use. He denied experiencing symptoms of alcohol withdrawal.

Regarding his medical history, the patient admitted to having had seizures, including two episodes that he said required hospitalization. He described these episodes as right-hand “tingling” (paresthesias), accompanied by right-facial numbness and aphasia. The patient said his physician had instructed him to take “a few phenytoin pills” whenever these episodes occurred. He reported that the medication usually helped resolve his symptoms. He said he had taken phenytoin shortly before his current presentation.

According to friends of the patient who were questioned, he had had noticeable memory problems during the previous six to eight months. They said that he often told the same joke, day after day. His speech had become increasingly slurred, even when he was not drinking.

Once the patient’s medical records were retrieved, it was revealed that he had been hospitalized twice for witnessed grand mal seizures about six months before his current admission; he had been drinking alcohol prior to both episodes. He underwent electroencephalography (EEG) during one of these hospitalizations, with results reported as normal. On both occasions, the patient was discharged with phenytoin and was instructed to follow up with his primary care provider and neurologist.

The patient, who reported working in customer service, had no known allergies. He claimed to drink one or two 40-ounce beers twice per week and admitted to occasional cocaine use. Of significance in his family history was a fatal MI in his mother. Although the patient denied any history of rashes or lesions, his current delirium made it impossible to obtain a reliable sexual history; a friend who was questioned, however, described the patient as promiscuous.

On initial physical examination, the man was afebrile, tachycardic, and somewhat combative with the ED staff. He was fully oriented to self but only partially to place and time.

His right pupil was 3+ and his left pupil was 2+, with neither reactive to light. He spoke with tangential speech and his gait was unsteady, but no other significant abnormalities were noted. A full assessment revealed no rashes or other lesions.

Significant laboratory findings included a low level of phenytoin, a negative blood alcohol level, presence of cocaine on urine drug screening, and normal levels of thyroid-stimulating hormone (TSH), vitamin B12, and folate. The patient’s serum VDRL (venereal disease research laboratory) titer was positive at 1:256.

Electroencephalography showed diffuse slowing, and brain CT performed in the ED showed atrophy that was mild but appropriate for a person of the patient’s age, with no evidence of a cerebrovascular accident (CVA). Aneurysm was ruled out by CT angiography of the brain. MRI revealed persistent increased signal in the subarachnoid space.

The patient was admitted with an initial diagnosis of paranoid delusional psychosis and monitored for alcohol withdrawal. He was given lorazepam as needed for agitation. Consultations were arranged with the psychiatry service regarding his delusions, and with neurology to determine whether to continue phenytoin.

The patient showed little response during the next several days. Based on positive results on serum VDRL with high titer, the presence of Argyll-Robertson pupils on exam, and his history of dementia-like symptoms, a lumbar puncture was performed to rule out neurosyphilis. In the patient’s cerebral spinal fluid (CSF) analysis, the first tube was clear and colorless, with 72 cells (28% neutrophils, 59% lymphocytes); glucose, 64 mg/dL; and total protein, 117 mg/dL. The fourth tube had 34 cells (17% neutrophils, 65% lymphocytes) and a positive VDRL titer at 1:128. Results from a serum syphilis immunoglobulin G (IgG) test were positive, and HIV antibody testing was nonreactive, confirming the diagnosis of neurosyphilis.

The hospital’s infectious disease (ID) team recommended treatment with IV penicillin for 14 days. Once this was completed, the patient was discharged with instructions to follow up at the ID clinic in three months for a repeat CSF VDRL titer to monitor for resolution of the disease. His prescription for phenytoin was discontinued.

At the time of discharge, it was noted that the patient showed no evidence of having regained cognitive function. He was deemed by the psychiatry service to lack decision-making capacity—a likely sequelae of untreated neurosyphilis of unknown duration.

He did return to the ID clinic six months after his discharge. At that visit, a VDRL serum titer was drawn with a result of 1:64, a decrease from 1:128. His syphilis IgG remained positive, however.

Discussion
Definition and Epidemiology
Syphilis is commonly known as a sexually transmitted disease with primary, secondary, and tertiary (early and late latent) stages.¹ Neurosyphilis is defined as a manifestation of the inflammatory response to invasion over decades by the Treponema pallidum spirochete in the CSF as a result of untreated primary and/or secondary syphilis.² About one in 10 patients with untreated syphilis will experience neurologic involvement.^3,4 Before 2005, neurosyphilis was required to be reported as a specific stage of syphilis (ie, a manifestation of tertiary syphilis4), but now should be reported as syphilis with neurologic manifestations.⁵

A reportable infectious disease, syphilis was widespread until the advent of penicillin. According to CDC statistics,⁶ the number of reported cases of primary and secondary syphilis has declined steadily since 1943. In the late 1970s and early 1980s, the number of tertiary cases also began to plateau, likely as a result of earlier diagnosis and more widespread use of penicillin. Recent case reports suggest greater prevalence of syphilis among men than women and increased incidence among men who have sex with men.⁷

Pathogenesis
Syphilis is most commonly spread by sexual contact or contact with an infected primary lesion (chancre). Less likely routes of transmission are placental passage or blood transfusion. Infectivity is greatest in the early disease stages.⁸

Primary syphilis is marked by transmission of the spirochete, ending with development of secondary syphilis (usually two to 12 weeks after transmission). A chancre commonly develops but is often missed by patients because it is painless and can heal spontaneously.⁷ The chancre is also often confused with two other sources of genital lesions, herpes simplex (genital herpes) and Haemophilus ducreyi (chancroid). In two-thirds of cases of untreated primary syphilis, the infection clears spontaneously, but in the remaining one-third, the disease progresses.⁸

Secondary syphilis, with or without presence of a chancre, manifests with constitutional symptoms, including lymphadenopathy, fever, headache, and malaise. Patients in this disease phase may also present with a generalized, nonpruritic, macular to maculopapular or pustular rash. The rash can affect the skin of the trunk, the proximal extremities, and the palms and soles. Ocular involvement may occur, especially in patients who are coinfected with HIV.⁸ In either primary or secondary syphilis, infection can invade the central nervous system.¹

During latent syphilis, patients show serologic conversion without overt symptoms. Early latent syphilis is defined as infection within the previous year, as demonstrated by conversion from negative to positive testing, or an increase in titers within the previous year. Any case occurring after one year is defined as late or unknown latent syphilis.⁸

Tertiary syphilis is marked by complications resulting from untreated syphilis; affected patients commonly experience central nervous system and cardiovascular involvement. Gummatous disease is seen in 15% of patients.¹

The early stages of neurosyphilis may be asymptomatic, acute meningeal, and meningovascular.^1,4,8,9 Only 5% of patients with early neurosyphilis are symptomatic, with the added potential for cranial neuritis or ocular involvement.¹ The late stages of neurosyphilis are detailed in the table.^1,4,8

Diagnosis
A diagnosis of syphilis is made by testing blood samples or scrapings from a lesion. In patients with suspected syphilis, rapid plasma reagin (RPR) testing or a VDRL titer is commonly ordered. When results are positive, a serum treponemal test is recommended to confirm a diagnosis of syphilis. Options include the fluorescent treponemal antibody absorption test (FTA-ABS) and the microhemagglutinin assay for antibody to T pallidum (MHA-TP).⁵

If neurologic symptoms are present, a CSF sample should be obtained, followed by the same testing. A confirmed diagnosis of neurosyphilis is defined by the CDC as syphilis at any stage that meets laboratory criteria for neurosyphilis⁵; these include increased CSF protein or an elevated CSF leukocyte count with no other known cause, and clinical signs or symptoms without other known causes.⁷

Treatment
Treatment of syphilis generally consists of penicillin, administered intramuscularly (IM) or IV, depending on the stage. According to 2006 guidelines from the CDC,^10,11 treatment for adults with primary and secondary syphilis is a single dose of IM penicillin G, 2.4 million units. If neurosyphilis is suspected, recommended treatment is IV penicillin G, 18 to 24 million units per day divided into six doses (ie, 3 to 4 million units every four hours) or continuous pump infusion for 10 to 14 days.^10-12 Follow-up is recommended by monitoring CSF titers to ensure clearance of infection; retreatment may be required if CSF abnormalities persist after two years.¹¹

Patients with a penicillin allergy should undergo desensitization, as penicillin is the preferred agent; the potential exists for cross-reactivity with ceftriaxone, a possible alternative for patients with neurosyphilis.¹¹ All patients diagnosed with syphilis should also be tested for HIV and other sexually transmitted diseases.^10-12

The prognosis of patients treated for neurosyphilis is generally good if the condition is diagnosed and treated early. In patients with cerebral atrophy, frontal lesions, dementia, or tabes dorsalis, the potential for recovery decreases.^2,13,14

Teaching Points
There are several teaching points to take away from this case:

• Remember to rule out a CVA in any patient who presents with numbness, paresthesias, or slurred speech. In this case, a brain CT and CT angiography of the brain were both obtained in the ED before the patient was admitted. They both yielded negative results; because the patient’s history was consistent with alcohol and drug use and he had a history of seizures, he was monitored closely for signs of withdrawal or further seizure.

• Phenytoin is an antiepileptic agent whose use requires proper patient education and drug level monitoring. Appropriate follow-up must be ensured before phenytoin therapy is begun, as toxicity can result in nystagmus, ataxia, slurred speech, decreased coordination, mental confusion, and possibly death.^15,16

• For patients with a suspected acute change in mental status, a workup is required and should be tailored appropriately, based on findings. This should include, but not be limited to, a thorough history and physical exam, CT of the brain (to rule out an acute brain injury¹⁷), and, if warranted, MRI of the brain. Also, a urine drug screen and alcohol level, a complete blood count, a TSH level (to evaluate for altered thyroid function that may explain mental status changes), comprehensive panel, RPR testing and/or a VDRL titer should be obtained, depending on the facility’s protocol^18,19; at some facilities, a treponemal test, rather than VDRL, is being obtained at the outset.²⁰ Levels of vitamin B12 (as part of the dementia workup), folate, thiamine, and ammonia (in patients with suspected liver disease) can also be obtained in patients with change in mental status.^18,19 Urinalysis should not be overlooked to check for a urinary tract infection, especially in elderly patients.²¹

• If primary syphilis is suspected, treatment must be undertaken.²⁰

Conclusion
Despite the decline seen since the 1940s in cases of primary and secondary syphilis, and the effectiveness of penicillin in treating the infection early, patients with late-stage syphilis, including those with neurosyphilis, may still present to the emergency care, urgent care, or primary care setting. Immediate treatment with penicillin is recommended to achieve an optimal prognosis for the affected patient.

The benefits of minimally invasive surgery—including less pain, faster recovery, and improved cosmesis—are well known.^1,2 Standard laparotomy has been replaced by multiple-port operative laparoscopy for a great array of procedures, and advances in medical technology allow for a minimally invasive surgical approach even when a surgeon is faced with complex pathology.

Single-port laparoscopic surgery (SPLS) represents the latest advance in minimally invasive surgery. Using flexible endoscopes and articulating instruments, the surgeon can complete complex procedures through a single 2-cm incision in the abdomen. The incision is usually placed in the umbilicus, where it is easily hidden.^3-8

Since the first laparoscopic hysterectomy through a single incision was performed 20 years ago, SPLS has been used successfully to perform nephrectomy, prostatectomy, hemicolectomy, cholecystectomy, splenectomy, intussusception reduction, gastrostomy tube placement, thoracoscopic lung biopsy, thoracoscopic decortication, and appendectomy.^4-7

In gynecology, SPLS has been used to perform oophorectomy, salpingectomy, bilateral tubal ligation, ovarian cystectomy, surgical treatment of ectopic pregnancy, and both total and partial hysterectomy.^7-11 At least two recent studies have concluded that SPLS is an acceptable way to treat many benign and malignant gynecologic conditions that are currently treated using multiport laparoscopy.^3,11

This article outlines our approach to SPLS in the gynecologic patient and provides an overview of instrumentation, with the aim of allowing you to consider whether this approach might be feasible in your surgical practice, at your institution.

Unique setup required

When SPLS is performed through the umbilicus, the instruments must be held closer to the midline and more cephalad than during conventional laparoscopy to permit adequate visualization and manipulation. For this reason, the surgeon needs to assume a position higher over the torso and thorax of the patient, and both of the patient’s arms need to be tucked. Place the patient in a dorsal lithotomy position with a uterine manipulator in place to facilitate surgery—even when the uterus will be preserved and surgery involves only the adnexae.

With appropriate equipment and positioning, visualization and manipulation of anatomy are comparable to those of standard multiport laparoscopy.

New instruments simplify SPLS

Innovative surgical instruments allow for appropriate hand positioning outside the abdomen and minimize the internal collision of instruments brought through a single midline incision (FIGURE 1). A variety of single-port options are available, each with a unique patented design and method of insertion. In fact, the development of ports with multiple instrument channels has revolutionized SPLS.

FIGURE 1 Setup
Desired triangulation of instruments in SPLS setup.Before true single ports became available, it was necessary to place three 5-mm low-profile trocars in the fascia at three separate sites through a single skin incision. Pneumoperitoneum was established with a Veress needle, but the fascial incisions gradually merged with repeated cannula manipulation, producing air leaks.

Today, multiple-channel ports are placed using an open technique into a single skin and fascial incision. Trocars and instruments of varying size can be exchanged with ease without jeopardizing pneumoperitoneum.

Among the options:

• the SILS Port (Covidien) – a soft, flexible, three-channel port that allows for placement of blunt trocars ranging in size from 5 mm to 12 mm (FIGURE 2)
• the TriPort (Olympus America) – two flexible rings joined by a sleeve and multiple-channel port (FIGURE 3)
• GelPOINT Advanced Access Platform (Applied Medical) – a system constructed of synthetic gel material and consisting of a “GelSeal” cap, cannulas, and seals to accommodate 5-mm to 10-mm instrumentation (FIGURE 4).

We have found that all three devices allow for good range of motion while maintaining pneumoperitoneum.

(A recent article from Korea reports an inventive technique to perform single-incision laparoscopy using standard instrumentation: The authors fitted a self-retaining ring retractor with a surgical glove that had three of the fingers cut off and replaced by trocars.¹²)

FIGURE 2 SILS Port
The SILS Port is a soft, flexible, three-channel port that allows for placement of blunt trocars ranging in size from 5 mm to 12 mm.

FIGURE 3 TriPort
The TriPort system comprises two flexible rings joined by a sleeve and multiple-channel port.

FIGURE 4 GelPOINT
The GelPOINT Advanced Access Platform is constructed of synthetic gel material and accommodates 5-mm to 10-mm instrumentation.

A flexible laparoscope improves visualization

The ability to visualize the operative field is vital to any surgery, including SPLS. Use of a flexible laparoscope facilitates uncompromised visualization of the entire pelvis (FIGURE 5). Outside the abdomen, the flexible camera can be held laterally and away from the midline to help reduce the clashing of instruments and hands.

FIGURE 5 Flexible-tip laparoscope
A flexible-tip laparoscope ensures good visualization of the surgical field.If a flexible laparoscope is not available, a rigid 30-degree or 45-degree angled scope can be used, although visualization may be limited and adequate triangulation of instruments may be difficult to achieve.

When using a rigid laparoscope, a light cord that inserts into the back of the camera is necessary; otherwise, a 90-degree light cord adapter can be purchased.

Design enhancements facilitate coordination of instruments

One of the disadvantages of SPLS has been the restriction of movement that arises because of the close proximity of instruments and instrument handles. The latest designs have made articulation possible for tissue graspers, scissors, vessel sealers, and scopes.^9,10 The value of articulation is apparent inside the abdomen, where it allows perfect positioning of the area of dissection. Outside the abdomen, the handles can be arranged in an angled pattern to allow the surgeon and assistant to operate comfortably (FIGURE 1).

In a four-handed procedure, one hand is on the camera, one on the uterine manipulator, and the remaining two hands operate the articulating grasper, vessel sealer, or needle driver, depending on the task.

Standard straight instruments can also be used for portions of the procedure.

Dissection and hemostasis are achieved in a manner similar to that of conventional laparoscopy. Our instrument of choice is an enhanced bipolar instrument, although harmonic and traditional biopolar energy can be used as well, depending on the preference of the surgeon.

The latest instruments are designed to dissect, cauterize, and cut, thereby decreasing the number of instrument exchanges necessary.

With the right aids, suturing can be simplified

Suturing through a single port can be a challenge. When possible, closure of the vaginal cuff following a total laparoscopic or laparoscopic-assisted vaginal hysterectomy should be performed from below. When endoscopic suturing is required, standard suturing using both intracorporeal and extracorporeal methods is possible.

Suturing aids such as the Endo Stitch (Covidien) or Lapra-Ty (Ethicon) are helpful. One author recommends Quill bidirectional, self-retaining suture with barbs (Angiotech) to avoid the need for knot-tying.⁶ (For more on self-retaining suture, see “Barbed suture, now in the toolbox of minimally invasive gyn surgery,” by Jon I. Einarsson, MD, MPH, and James A. Greenberg, MD, in the September 2009 issue at obgmanagement.com.)

The MiniLap (Stryker) is a 2.3-mm grasper that is inserted percutaneously directly through the abdominal wall without an incision. It can be used to set the needle on the needle driver or manipulate tissue while suturing. The resulting skin incision is barely visible and does not require closure.

Options are varied for specimen removal

Small specimens can be removed directly through a single-port system that has been opened, or they can be extracted after the system is removed, with rapid desufflation (FIGURE 6).

FIGURE 6 Single-incision oophorectomy
An ovary and tube removed through a single incision using the A) TriPort and B) SILS Port systems.Compared with conventional laparoscopy, the larger incision associated with single-port surgery facilitates specimen removal. Larger or potentially malignant specimens can be placed into an EndoCatch bag (Covidien) inserted through the single-incision 10-mm cannula (FIGURE 7).

FIGURE 7 Specimen removal
In this case, the specimen was placed in a 10-mm EndoCatch bag and removed through the 10-mm cannula of the SILS Port.In total laparoscopic hysterectomy or laparoscopic-assisted vaginal hysterectomy, the uterus is removed through the vagina. In supracervical hysterectomy, a small uterus can be removed through the cul-de-sac or directly through the single incision after placement in a bag.

When morcellation is required, the instrument can be placed through the cul-desac, cervix, or a single port. The morcellator can be placed directly through the SPLS port while utilizing the flexible scope in an angled direction (looking back toward the morcellator) for complete visualization (note: Covidien does not recommend this usage).

Transcervical tissue morcellation has also been described. In this approach, the cervix is dilated once the uterine body has been amputated, and the tissue morcellator is inserted through the cervix while the surgeon maintains visualization from above.^6,13

How to master the technique

Many patients desire SPLS for its superior cosmetic outcome, but the approach may not always be appropriate. Depending on the procedure and characteristics of the patient (TABLE), multiple-port laparoscopy may be a better option. When a surgeon first attempts SPLS, we recommend that it be limited to the treatment of adnexal pathology only.

In your early SPlS cases, look for these patient characteristics

By using the techniques described in this article and selecting patients carefully, the surgeon can develop expertise in SPLS.^11,14 During the learning process, the use of additional ports or Mini-Lap instruments (Stryker) can reduce the challenges of more difficult procedures and should be considered without reservation, as should the use of articulating accessory instruments and flexible or angled laparoscopes.

Although the clinical benefits of SPLS have yet to be determined, the cosmetic advantage of a single, hidden, umbilical incision likely increases patient satisfaction.

Clearly, the goal of SPLS is to use technology in a way that offers all of the benefits of traditional multiport laparoscopy without any of the limitations. Further study is required to determine whether SPLS meets this standard and, more important, whether it has any advantages over conventional techniques.

We want to hear from you! Tell us what you think.

The benefits of minimally invasive surgery—including less pain, faster recovery, and improved cosmesis—are well known.^1,2 Standard laparotomy has been replaced by multiple-port operative laparoscopy for a great array of procedures, and advances in medical technology allow for a minimally invasive surgical approach even when a surgeon is faced with complex pathology.

Single-port laparoscopic surgery (SPLS) represents the latest advance in minimally invasive surgery. Using flexible endoscopes and articulating instruments, the surgeon can complete complex procedures through a single 2-cm incision in the abdomen. The incision is usually placed in the umbilicus, where it is easily hidden.^3-8

Since the first laparoscopic hysterectomy through a single incision was performed 20 years ago, SPLS has been used successfully to perform nephrectomy, prostatectomy, hemicolectomy, cholecystectomy, splenectomy, intussusception reduction, gastrostomy tube placement, thoracoscopic lung biopsy, thoracoscopic decortication, and appendectomy.^4-7

In gynecology, SPLS has been used to perform oophorectomy, salpingectomy, bilateral tubal ligation, ovarian cystectomy, surgical treatment of ectopic pregnancy, and both total and partial hysterectomy.^7-11 At least two recent studies have concluded that SPLS is an acceptable way to treat many benign and malignant gynecologic conditions that are currently treated using multiport laparoscopy.^3,11

This article outlines our approach to SPLS in the gynecologic patient and provides an overview of instrumentation, with the aim of allowing you to consider whether this approach might be feasible in your surgical practice, at your institution.

Unique setup required

When SPLS is performed through the umbilicus, the instruments must be held closer to the midline and more cephalad than during conventional laparoscopy to permit adequate visualization and manipulation. For this reason, the surgeon needs to assume a position higher over the torso and thorax of the patient, and both of the patient’s arms need to be tucked. Place the patient in a dorsal lithotomy position with a uterine manipulator in place to facilitate surgery—even when the uterus will be preserved and surgery involves only the adnexae.

With appropriate equipment and positioning, visualization and manipulation of anatomy are comparable to those of standard multiport laparoscopy.

New instruments simplify SPLS

Innovative surgical instruments allow for appropriate hand positioning outside the abdomen and minimize the internal collision of instruments brought through a single midline incision (FIGURE 1). A variety of single-port options are available, each with a unique patented design and method of insertion. In fact, the development of ports with multiple instrument channels has revolutionized SPLS.

FIGURE 1 Setup
Desired triangulation of instruments in SPLS setup.Before true single ports became available, it was necessary to place three 5-mm low-profile trocars in the fascia at three separate sites through a single skin incision. Pneumoperitoneum was established with a Veress needle, but the fascial incisions gradually merged with repeated cannula manipulation, producing air leaks.

Today, multiple-channel ports are placed using an open technique into a single skin and fascial incision. Trocars and instruments of varying size can be exchanged with ease without jeopardizing pneumoperitoneum.

Among the options:

• the SILS Port (Covidien) – a soft, flexible, three-channel port that allows for placement of blunt trocars ranging in size from 5 mm to 12 mm (FIGURE 2)
• the TriPort (Olympus America) – two flexible rings joined by a sleeve and multiple-channel port (FIGURE 3)
• GelPOINT Advanced Access Platform (Applied Medical) – a system constructed of synthetic gel material and consisting of a “GelSeal” cap, cannulas, and seals to accommodate 5-mm to 10-mm instrumentation (FIGURE 4).

We have found that all three devices allow for good range of motion while maintaining pneumoperitoneum.

(A recent article from Korea reports an inventive technique to perform single-incision laparoscopy using standard instrumentation: The authors fitted a self-retaining ring retractor with a surgical glove that had three of the fingers cut off and replaced by trocars.¹²)

FIGURE 2 SILS Port
The SILS Port is a soft, flexible, three-channel port that allows for placement of blunt trocars ranging in size from 5 mm to 12 mm.

FIGURE 3 TriPort
The TriPort system comprises two flexible rings joined by a sleeve and multiple-channel port.

FIGURE 4 GelPOINT
The GelPOINT Advanced Access Platform is constructed of synthetic gel material and accommodates 5-mm to 10-mm instrumentation.

A flexible laparoscope improves visualization

The ability to visualize the operative field is vital to any surgery, including SPLS. Use of a flexible laparoscope facilitates uncompromised visualization of the entire pelvis (FIGURE 5). Outside the abdomen, the flexible camera can be held laterally and away from the midline to help reduce the clashing of instruments and hands.

FIGURE 5 Flexible-tip laparoscope
A flexible-tip laparoscope ensures good visualization of the surgical field.If a flexible laparoscope is not available, a rigid 30-degree or 45-degree angled scope can be used, although visualization may be limited and adequate triangulation of instruments may be difficult to achieve.

When using a rigid laparoscope, a light cord that inserts into the back of the camera is necessary; otherwise, a 90-degree light cord adapter can be purchased.

Design enhancements facilitate coordination of instruments

One of the disadvantages of SPLS has been the restriction of movement that arises because of the close proximity of instruments and instrument handles. The latest designs have made articulation possible for tissue graspers, scissors, vessel sealers, and scopes.^9,10 The value of articulation is apparent inside the abdomen, where it allows perfect positioning of the area of dissection. Outside the abdomen, the handles can be arranged in an angled pattern to allow the surgeon and assistant to operate comfortably (FIGURE 1).

In a four-handed procedure, one hand is on the camera, one on the uterine manipulator, and the remaining two hands operate the articulating grasper, vessel sealer, or needle driver, depending on the task.

Standard straight instruments can also be used for portions of the procedure.

Dissection and hemostasis are achieved in a manner similar to that of conventional laparoscopy. Our instrument of choice is an enhanced bipolar instrument, although harmonic and traditional biopolar energy can be used as well, depending on the preference of the surgeon.

The latest instruments are designed to dissect, cauterize, and cut, thereby decreasing the number of instrument exchanges necessary.

With the right aids, suturing can be simplified

Suturing through a single port can be a challenge. When possible, closure of the vaginal cuff following a total laparoscopic or laparoscopic-assisted vaginal hysterectomy should be performed from below. When endoscopic suturing is required, standard suturing using both intracorporeal and extracorporeal methods is possible.

Suturing aids such as the Endo Stitch (Covidien) or Lapra-Ty (Ethicon) are helpful. One author recommends Quill bidirectional, self-retaining suture with barbs (Angiotech) to avoid the need for knot-tying.⁶ (For more on self-retaining suture, see “Barbed suture, now in the toolbox of minimally invasive gyn surgery,” by Jon I. Einarsson, MD, MPH, and James A. Greenberg, MD, in the September 2009 issue at obgmanagement.com.)

The MiniLap (Stryker) is a 2.3-mm grasper that is inserted percutaneously directly through the abdominal wall without an incision. It can be used to set the needle on the needle driver or manipulate tissue while suturing. The resulting skin incision is barely visible and does not require closure.

Options are varied for specimen removal

Small specimens can be removed directly through a single-port system that has been opened, or they can be extracted after the system is removed, with rapid desufflation (FIGURE 6).

FIGURE 6 Single-incision oophorectomy
An ovary and tube removed through a single incision using the A) TriPort and B) SILS Port systems.Compared with conventional laparoscopy, the larger incision associated with single-port surgery facilitates specimen removal. Larger or potentially malignant specimens can be placed into an EndoCatch bag (Covidien) inserted through the single-incision 10-mm cannula (FIGURE 7).

FIGURE 7 Specimen removal
In this case, the specimen was placed in a 10-mm EndoCatch bag and removed through the 10-mm cannula of the SILS Port.In total laparoscopic hysterectomy or laparoscopic-assisted vaginal hysterectomy, the uterus is removed through the vagina. In supracervical hysterectomy, a small uterus can be removed through the cul-de-sac or directly through the single incision after placement in a bag.

When morcellation is required, the instrument can be placed through the cul-desac, cervix, or a single port. The morcellator can be placed directly through the SPLS port while utilizing the flexible scope in an angled direction (looking back toward the morcellator) for complete visualization (note: Covidien does not recommend this usage).

Transcervical tissue morcellation has also been described. In this approach, the cervix is dilated once the uterine body has been amputated, and the tissue morcellator is inserted through the cervix while the surgeon maintains visualization from above.^6,13

How to master the technique

Many patients desire SPLS for its superior cosmetic outcome, but the approach may not always be appropriate. Depending on the procedure and characteristics of the patient (TABLE), multiple-port laparoscopy may be a better option. When a surgeon first attempts SPLS, we recommend that it be limited to the treatment of adnexal pathology only.

In your early SPlS cases, look for these patient characteristics

By using the techniques described in this article and selecting patients carefully, the surgeon can develop expertise in SPLS.^11,14 During the learning process, the use of additional ports or Mini-Lap instruments (Stryker) can reduce the challenges of more difficult procedures and should be considered without reservation, as should the use of articulating accessory instruments and flexible or angled laparoscopes.

Although the clinical benefits of SPLS have yet to be determined, the cosmetic advantage of a single, hidden, umbilical incision likely increases patient satisfaction.

Clearly, the goal of SPLS is to use technology in a way that offers all of the benefits of traditional multiport laparoscopy without any of the limitations. Further study is required to determine whether SPLS meets this standard and, more important, whether it has any advantages over conventional techniques.

We want to hear from you! Tell us what you think.

The benefits of minimally invasive surgery—including less pain, faster recovery, and improved cosmesis—are well known.^1,2 Standard laparotomy has been replaced by multiple-port operative laparoscopy for a great array of procedures, and advances in medical technology allow for a minimally invasive surgical approach even when a surgeon is faced with complex pathology.

Single-port laparoscopic surgery (SPLS) represents the latest advance in minimally invasive surgery. Using flexible endoscopes and articulating instruments, the surgeon can complete complex procedures through a single 2-cm incision in the abdomen. The incision is usually placed in the umbilicus, where it is easily hidden.^3-8

Since the first laparoscopic hysterectomy through a single incision was performed 20 years ago, SPLS has been used successfully to perform nephrectomy, prostatectomy, hemicolectomy, cholecystectomy, splenectomy, intussusception reduction, gastrostomy tube placement, thoracoscopic lung biopsy, thoracoscopic decortication, and appendectomy.^4-7

In gynecology, SPLS has been used to perform oophorectomy, salpingectomy, bilateral tubal ligation, ovarian cystectomy, surgical treatment of ectopic pregnancy, and both total and partial hysterectomy.^7-11 At least two recent studies have concluded that SPLS is an acceptable way to treat many benign and malignant gynecologic conditions that are currently treated using multiport laparoscopy.^3,11

This article outlines our approach to SPLS in the gynecologic patient and provides an overview of instrumentation, with the aim of allowing you to consider whether this approach might be feasible in your surgical practice, at your institution.

Unique setup required

When SPLS is performed through the umbilicus, the instruments must be held closer to the midline and more cephalad than during conventional laparoscopy to permit adequate visualization and manipulation. For this reason, the surgeon needs to assume a position higher over the torso and thorax of the patient, and both of the patient’s arms need to be tucked. Place the patient in a dorsal lithotomy position with a uterine manipulator in place to facilitate surgery—even when the uterus will be preserved and surgery involves only the adnexae.

With appropriate equipment and positioning, visualization and manipulation of anatomy are comparable to those of standard multiport laparoscopy.

New instruments simplify SPLS

Innovative surgical instruments allow for appropriate hand positioning outside the abdomen and minimize the internal collision of instruments brought through a single midline incision (FIGURE 1). A variety of single-port options are available, each with a unique patented design and method of insertion. In fact, the development of ports with multiple instrument channels has revolutionized SPLS.

FIGURE 1 Setup
Desired triangulation of instruments in SPLS setup.Before true single ports became available, it was necessary to place three 5-mm low-profile trocars in the fascia at three separate sites through a single skin incision. Pneumoperitoneum was established with a Veress needle, but the fascial incisions gradually merged with repeated cannula manipulation, producing air leaks.

Today, multiple-channel ports are placed using an open technique into a single skin and fascial incision. Trocars and instruments of varying size can be exchanged with ease without jeopardizing pneumoperitoneum.

Among the options:

• the SILS Port (Covidien) – a soft, flexible, three-channel port that allows for placement of blunt trocars ranging in size from 5 mm to 12 mm (FIGURE 2)
• the TriPort (Olympus America) – two flexible rings joined by a sleeve and multiple-channel port (FIGURE 3)
• GelPOINT Advanced Access Platform (Applied Medical) – a system constructed of synthetic gel material and consisting of a “GelSeal” cap, cannulas, and seals to accommodate 5-mm to 10-mm instrumentation (FIGURE 4).

We have found that all three devices allow for good range of motion while maintaining pneumoperitoneum.

(A recent article from Korea reports an inventive technique to perform single-incision laparoscopy using standard instrumentation: The authors fitted a self-retaining ring retractor with a surgical glove that had three of the fingers cut off and replaced by trocars.¹²)

FIGURE 2 SILS Port
The SILS Port is a soft, flexible, three-channel port that allows for placement of blunt trocars ranging in size from 5 mm to 12 mm.

FIGURE 3 TriPort
The TriPort system comprises two flexible rings joined by a sleeve and multiple-channel port.

FIGURE 4 GelPOINT
The GelPOINT Advanced Access Platform is constructed of synthetic gel material and accommodates 5-mm to 10-mm instrumentation.

A flexible laparoscope improves visualization

The ability to visualize the operative field is vital to any surgery, including SPLS. Use of a flexible laparoscope facilitates uncompromised visualization of the entire pelvis (FIGURE 5). Outside the abdomen, the flexible camera can be held laterally and away from the midline to help reduce the clashing of instruments and hands.

FIGURE 5 Flexible-tip laparoscope
A flexible-tip laparoscope ensures good visualization of the surgical field.If a flexible laparoscope is not available, a rigid 30-degree or 45-degree angled scope can be used, although visualization may be limited and adequate triangulation of instruments may be difficult to achieve.

When using a rigid laparoscope, a light cord that inserts into the back of the camera is necessary; otherwise, a 90-degree light cord adapter can be purchased.

Design enhancements facilitate coordination of instruments

One of the disadvantages of SPLS has been the restriction of movement that arises because of the close proximity of instruments and instrument handles. The latest designs have made articulation possible for tissue graspers, scissors, vessel sealers, and scopes.^9,10 The value of articulation is apparent inside the abdomen, where it allows perfect positioning of the area of dissection. Outside the abdomen, the handles can be arranged in an angled pattern to allow the surgeon and assistant to operate comfortably (FIGURE 1).

In a four-handed procedure, one hand is on the camera, one on the uterine manipulator, and the remaining two hands operate the articulating grasper, vessel sealer, or needle driver, depending on the task.

Standard straight instruments can also be used for portions of the procedure.

Dissection and hemostasis are achieved in a manner similar to that of conventional laparoscopy. Our instrument of choice is an enhanced bipolar instrument, although harmonic and traditional biopolar energy can be used as well, depending on the preference of the surgeon.

The latest instruments are designed to dissect, cauterize, and cut, thereby decreasing the number of instrument exchanges necessary.

With the right aids, suturing can be simplified

Suturing through a single port can be a challenge. When possible, closure of the vaginal cuff following a total laparoscopic or laparoscopic-assisted vaginal hysterectomy should be performed from below. When endoscopic suturing is required, standard suturing using both intracorporeal and extracorporeal methods is possible.

Suturing aids such as the Endo Stitch (Covidien) or Lapra-Ty (Ethicon) are helpful. One author recommends Quill bidirectional, self-retaining suture with barbs (Angiotech) to avoid the need for knot-tying.⁶ (For more on self-retaining suture, see “Barbed suture, now in the toolbox of minimally invasive gyn surgery,” by Jon I. Einarsson, MD, MPH, and James A. Greenberg, MD, in the September 2009 issue at obgmanagement.com.)

The MiniLap (Stryker) is a 2.3-mm grasper that is inserted percutaneously directly through the abdominal wall without an incision. It can be used to set the needle on the needle driver or manipulate tissue while suturing. The resulting skin incision is barely visible and does not require closure.

Options are varied for specimen removal

Small specimens can be removed directly through a single-port system that has been opened, or they can be extracted after the system is removed, with rapid desufflation (FIGURE 6).

FIGURE 6 Single-incision oophorectomy
An ovary and tube removed through a single incision using the A) TriPort and B) SILS Port systems.Compared with conventional laparoscopy, the larger incision associated with single-port surgery facilitates specimen removal. Larger or potentially malignant specimens can be placed into an EndoCatch bag (Covidien) inserted through the single-incision 10-mm cannula (FIGURE 7).

FIGURE 7 Specimen removal
In this case, the specimen was placed in a 10-mm EndoCatch bag and removed through the 10-mm cannula of the SILS Port.In total laparoscopic hysterectomy or laparoscopic-assisted vaginal hysterectomy, the uterus is removed through the vagina. In supracervical hysterectomy, a small uterus can be removed through the cul-de-sac or directly through the single incision after placement in a bag.

When morcellation is required, the instrument can be placed through the cul-desac, cervix, or a single port. The morcellator can be placed directly through the SPLS port while utilizing the flexible scope in an angled direction (looking back toward the morcellator) for complete visualization (note: Covidien does not recommend this usage).

Transcervical tissue morcellation has also been described. In this approach, the cervix is dilated once the uterine body has been amputated, and the tissue morcellator is inserted through the cervix while the surgeon maintains visualization from above.^6,13

How to master the technique

Many patients desire SPLS for its superior cosmetic outcome, but the approach may not always be appropriate. Depending on the procedure and characteristics of the patient (TABLE), multiple-port laparoscopy may be a better option. When a surgeon first attempts SPLS, we recommend that it be limited to the treatment of adnexal pathology only.

In your early SPlS cases, look for these patient characteristics

By using the techniques described in this article and selecting patients carefully, the surgeon can develop expertise in SPLS.^11,14 During the learning process, the use of additional ports or Mini-Lap instruments (Stryker) can reduce the challenges of more difficult procedures and should be considered without reservation, as should the use of articulating accessory instruments and flexible or angled laparoscopes.

Although the clinical benefits of SPLS have yet to be determined, the cosmetic advantage of a single, hidden, umbilical incision likely increases patient satisfaction.

Clearly, the goal of SPLS is to use technology in a way that offers all of the benefits of traditional multiport laparoscopy without any of the limitations. Further study is required to determine whether SPLS meets this standard and, more important, whether it has any advantages over conventional techniques.

We want to hear from you! Tell us what you think.

“Not all mood swings are bipolar disorder” (Current Psychiatry, February 2011, p. 38-52) is a highly relevant and helpful article with a glaring omission. There is no mention of the emotional lability and behavioral dyscontrol associated with abuse, trauma, and invalidation. “Mood swing” symptoms are prominent in developmental trauma disorder and complex posttraumatic stress disorder, although these diagnoses are not yet in the DSM. Unfortunately, the effects of abuse, trauma, and invalidation often are unrecognized in the differential diagnoses of these children and too often the “kneejerk” diagnoses of bipolar disorder, oppositional defiant disorder, and attention-deficit/hyperactivity disorder are inappropriately assigned, delaying the implementation of trauma theory-informed therapy.

Bradford B. Schwartz, MD
Private Practice
York, PA

The authors respond

We thank Dr. Schwartz for his comments regarding emotional lability and behavioral dyscontrol associated with children who have experienced trauma, abuse, and invalidation. An assessment for possible trauma always is part of the initial assessment of each child referred to our program. None of the patients discussed in our article had a history of abuse or trauma. Referrals to our pediatric mood disorders program initially are screened through the Cincinnati Children’s Hospital Psychiatric Intake and Response Center, which functions as triage, gathering psychiatric history, including assessing trauma, and children with a history of abuse and trauma are referred to other clinicians specializing in this area. But Dr. Schwartz’s point is well taken—trauma or abuse always should be part of the differential diagnosis of children and adolescents referred for mood swings.

Robert A. Kowatch, MD, PhD
Professor of Psychiatry and Pediatrics

Erin Monroe, CNS
Clinical Nurse Specialist
Division of Psychiatry

Sergio V. Delgado, MD
Associate Professor of Psychiatry
and Pediatrics
Cincinnati Children’s Hospital Medical Center
Cincinnati, OH

“Not all mood swings are bipolar disorder” (Current Psychiatry, February 2011, p. 38-52) is a highly relevant and helpful article with a glaring omission. There is no mention of the emotional lability and behavioral dyscontrol associated with abuse, trauma, and invalidation. “Mood swing” symptoms are prominent in developmental trauma disorder and complex posttraumatic stress disorder, although these diagnoses are not yet in the DSM. Unfortunately, the effects of abuse, trauma, and invalidation often are unrecognized in the differential diagnoses of these children and too often the “kneejerk” diagnoses of bipolar disorder, oppositional defiant disorder, and attention-deficit/hyperactivity disorder are inappropriately assigned, delaying the implementation of trauma theory-informed therapy.

Bradford B. Schwartz, MD
Private Practice
York, PA

The authors respond

We thank Dr. Schwartz for his comments regarding emotional lability and behavioral dyscontrol associated with children who have experienced trauma, abuse, and invalidation. An assessment for possible trauma always is part of the initial assessment of each child referred to our program. None of the patients discussed in our article had a history of abuse or trauma. Referrals to our pediatric mood disorders program initially are screened through the Cincinnati Children’s Hospital Psychiatric Intake and Response Center, which functions as triage, gathering psychiatric history, including assessing trauma, and children with a history of abuse and trauma are referred to other clinicians specializing in this area. But Dr. Schwartz’s point is well taken—trauma or abuse always should be part of the differential diagnosis of children and adolescents referred for mood swings.

Robert A. Kowatch, MD, PhD
Professor of Psychiatry and Pediatrics

Erin Monroe, CNS
Clinical Nurse Specialist
Division of Psychiatry

Sergio V. Delgado, MD
Associate Professor of Psychiatry
and Pediatrics
Cincinnati Children’s Hospital Medical Center
Cincinnati, OH

“Not all mood swings are bipolar disorder” (Current Psychiatry, February 2011, p. 38-52) is a highly relevant and helpful article with a glaring omission. There is no mention of the emotional lability and behavioral dyscontrol associated with abuse, trauma, and invalidation. “Mood swing” symptoms are prominent in developmental trauma disorder and complex posttraumatic stress disorder, although these diagnoses are not yet in the DSM. Unfortunately, the effects of abuse, trauma, and invalidation often are unrecognized in the differential diagnoses of these children and too often the “kneejerk” diagnoses of bipolar disorder, oppositional defiant disorder, and attention-deficit/hyperactivity disorder are inappropriately assigned, delaying the implementation of trauma theory-informed therapy.

Bradford B. Schwartz, MD
Private Practice
York, PA

The authors respond

We thank Dr. Schwartz for his comments regarding emotional lability and behavioral dyscontrol associated with children who have experienced trauma, abuse, and invalidation. An assessment for possible trauma always is part of the initial assessment of each child referred to our program. None of the patients discussed in our article had a history of abuse or trauma. Referrals to our pediatric mood disorders program initially are screened through the Cincinnati Children’s Hospital Psychiatric Intake and Response Center, which functions as triage, gathering psychiatric history, including assessing trauma, and children with a history of abuse and trauma are referred to other clinicians specializing in this area. But Dr. Schwartz’s point is well taken—trauma or abuse always should be part of the differential diagnosis of children and adolescents referred for mood swings.

Robert A. Kowatch, MD, PhD
Professor of Psychiatry and Pediatrics

Erin Monroe, CNS
Clinical Nurse Specialist
Division of Psychiatry

Sergio V. Delgado, MD
Associate Professor of Psychiatry
and Pediatrics
Cincinnati Children’s Hospital Medical Center
Cincinnati, OH

MS. F, age 66, requests genetic testing because she is concerned about mild memory difficulties, such as forgetting names and where she puts her keys or checkbook, and fears she may be developing Alzheimer’s disease (AD). Her mother and sister were diagnosed with AD in their early 60s. Ms. F has 20 years of education and reports no problems with driving, managing her finances, remembering to take her medications, or maintaining social activities, which her husband confirms.

Detailed questioning about anxiety and depressive symptoms reveals substantial worries about future cognitive decline and some concerns about her finances and her husband’s health. Ms. F says she occasionally feels down and has low energy but denies other depressive symptoms. She reports no sleep disturbances—including snoring and daytime sleepiness, which could indicate obstructive sleep apnea—which her husband confirms. Ms. F takes levothyroxine for hypothyroidism, atenolol for hypertension, aspirin and clopidogrel for coronary artery disease, and atorvastatin for hyperlipidemia. In addition, she provides a long list of over-the-counter (OTC) supplements—ginkgo, huperzine, ginseng, phosphatidylserine, B1, B12, folate, vitamin D, alpha-lipoic acid, and vinpocetine—that she takes to “protect” her brain from AD.

Subjective cognitive impairment (SCI) in older persons is a common condition with a largely unclear prognosis. Many older adults (age ≥65) express concern about mild cognitive problems—“senior moments”—such as word-finding difficulties and forgetfulness.¹ Individuals may wonder if walking into a room only to forget why might be the first sign of dementia. Some older adults try to counteract these memory problems by engaging in brain exercises—including costly computer games—and taking OTC “brain-enhancing” vitamins, herbal remedies, and other supplements.

Although some clinicians may view SCI as benign, that is not always true (Table l).^2-5 This article discusses the clinical significance of these mild cognitive complaints by examining:

• age-related cognitive decline (ARCD)
• SCI
• how SCI can be differentiated from more serious conditions, such as mild cognitive impairment (MCI) and early stages of AD and other dementias.

We also will discuss assessing and treating cognitive complaints. Although distinctions between SCI and ARCD may be controversial, evidence suggests clinicians need to adopt a more nuanced clinical approach.

Table 1

Why SCI should be taken seriously

‘Normal’ cognitive decline

ARCD is subtle decline in cognitive abilities, such as episodic memory, attention, and time needed to complete complex activities.^6,7 Individuals with ARCD might not have subjective memory complaints or objective cognitive deficits, and their ability to live independently may not be compromised.⁷ The degree of decline in ARCD may be smaller than previously thought.⁸ Park⁹ summarizes 4 main mechanisms thought to underlie age-related declines in cognition:

• reduced speed of processing
• decreased working memory capabilities
• declining inhibitory control (eg, impaired complex attentional capabilities)
• sensory changes (eg, visual and auditory deficits).

ARCD traditionally is thought to result from predictable changes in the brain associated with aging, such as reduced brain volume in the hippocampus and frontal lobes, loss of myelin, loss of synapses, and cytoskeletal changes.⁷ However, not all older adults experience ARCD. Some remain highly functional in their later years and continue to actively engage in life well into very old age.^6,9

Subjective cognitive impairment

One-quarter to one-half of community-dwelling older adults report subjective cognitive complaints, such as forgetfulness and word-finding difficulties.¹⁰ Patients with SCI do not show objective evidence of cognitive impairment on neuropsychological tests and their cognitive problems cause no functional decline.¹⁰

Preliminary evidence indicates that SCI may be a harbinger of further cognitive decline. Reisberg et al³ found that compared with patients without SCI, patients with SCI were 4.5 times more likely to develop MCI—cognitive difficulties that can be detected by cognitive tests, but do not cause functional decline—or dementia within 7 years.³ Studies also have suggested that SCI may be a pre-MCI stage of subsequent dementia.^11-13 AD generally has a long (10 to 12 years) and progressive prodromal phase before dementia onset and is characterized by successive emergence of cognitive deficits, memory complaints, depressive symptoms, and functional impairment.¹⁴

In light of this research, we believe patients with SCI and other risk factors for AD, such as a family history of AD, may be at higher risk of further cognitive and functional decline compared with individuals with ARCD and no AD risk factors. Therefore, patients with SCI and other risk factors for AD (Table 2)^15-19 may benefit from annual follow-up to determine if cognitive problems have progressed to MCI or AD.

SCI may be a response to subclinical alterations in neurobiology—a phenomenon known as reverse causality.²⁰ Biomarkers, such as cerebrospinal fluid levels of ß-amyloid and phosphorylated tau, and amyloid imaging using positron emission tomography may help identify AD in SCI patients.²¹ In these patients, SCI is a misnomer because the cognitive impairment is real—not “subjective”—but current tests are not sensitive enough to detect the cognitive decline the patient has recognized. This group of patients should be differentiated from individuals who may perceive typical cognitive aging (ARCD) as pathologic and complain about it. In the future, biomarkers may help differentiate these 2 groups.

Table 2

Factors that increase SCI patients’ risk for dementia

Mild cognitive impairment

MCI is similar to SCI because MCI patients may present with complaints of memory decline and other cognitive difficulties²² but neither condition is associated with significant impairment of daily activities.²³ The key difference is that patients with MCI demonstrate impaired performance on objective cognitive tests whereas SCI patients do not.²⁴ In our experience, office-based tests do not reliably differentiate the 2 conditions because many patients with SCI may show mild impairment in tests such as the Mini-Mental State Exam (MMSE)²⁵ but comprehensive neuropsychological testing reveals no objective cognitive deficits. Neuropsychological testing is essential to reliably differentiate SCI from MCI.

The distinction between SCI and MCI is clinically relevant because evidence suggests that MCI patients have a near-term risk of developing dementia, particularly AD.^22,23 In a longitudinal study of 76 individuals with MCI, 12% of patients progressed to AD each year compared with 1% to 2% of healthy older adults.²⁶ Patients with MCI are at increased risk of delirium (especially during hospitalization), falls, medication errors, and difficulty managing their finances.²⁴ Older adults with MCI also have increased mortality compared with older adults with normal cognitive functioning.²² Both SCI and MCI should be differentiated from mild dementia. Common dementias in older adults include:

• AD dementia
• Vascular dementia (may occur with or without AD)
• Lewy body dementia
• Frontotemporal dementia
• Parkinson’s disease dementia.

By definition, all dementia types are associated with impaired ability to perform daily activities and cognitive decline.²⁷

Assessing cognitive complaints

Evaluation of older adults’ cognitive complaints should begin with a thorough history to elicit symptoms of anxiety, depression, physical complaints, and any associated functional decline; a physical exam; and a comprehensive mental status examination. This initial evaluation should be followed by routine and specific investigations as indicated (Table 3).^22,24,28,29

In a 6-year study of 100 older adults with and without objective evidence of memory decline, both groups showed similar rates of cognitive complaints.³⁰ Also, researchers found no relationship between individuals’ perception of their cognitive functioning and performance on neuropsychological testing. Mood, education level, and apolipoprotein E epsilon 4 genotype status also did not correlate with participants’ subjective cognitive complaints. These findings highlight the need for objective test data to determine whether older adults’ memory complaints reflect pathologic changes in cognition. After a thorough diagnostic workup, some patients complaining of memory decline will have no detectable evidence of cognitive dysfunction or an identifiable cause. However, others may have identifiable causes of memory impairment (Table 4)^28,29,31,32—which could be treated—some will have MCI, and others may be in an early stage of dementia.

Table 3

Investigation of older adults with SCI

Table 4

Differential diagnosis of SCI

CASE CONTINUED: No measurable deficits

Ms. F’s medical history is remarkable for coronary artery disease, hypothyroidism, hypertension, hyperlipidemia, cataracts, arthritis, back surgery (secondary to spondylosis), and foot surgery. Ms. F denies a history of alcohol or illicit substance abuse. She smoked tobacco for 30 years (2 packs per day), but quit 5 years ago after her heart attack. Physical exam is unremarkable except for mild obesity (body mass index = 31 kg/m²).

Ms. F’s mental status exam reveals anxious mood and affect. Her recall is 2 out of 3 items. Her MMSE score is 29/30 (1 point lost on recall) and her Geriatric Depression Scale³³ score is 2/15, indicating minimal depressive symptoms. On neuropsychological testing, Ms. F demonstrates high average intellectual abilities; compared with others her age, she performs within expectations on all measures. That is, she performs within the above-average to low-average range on measures of attention, working memory, speed of processing, expressive language, learning, memory, visual spatial abilities, executive functioning, and knowledge of basic health and safety information.

Enhancing neuroplasticity

We recommend neuroplasticity-based interventions to treat SCI and promote healthy brain aging.^20,29 For a checklist clinicians can use to promote healthy brain aging and thus improve patients’ cognitive health see this article at CurrentPsychiatry. com. Table 5^1,29 lists cognitive strategies to improve memory and maintain cognitive vitality.

Enhancing brain plasticity and neurogenesis requires engaging older adults in demanding sensory, cognitive, and motor activities on an intensive basis.³⁴ Therapeutic stimulation of neuroplasticity and neurogenesis might contribute to functional “repair” of the diseased adult brain before damage to whole neuronal networks has ensued.²⁹ An important treatment component is reassuring patients with SCI that they do not have AD or MCI. Treating comorbid anxiety and depression and reversible causes of cognitive complaints is key to successful outcomes.

Table 5

Strategies to improve memory and maintain cognitive vitality

CASE CONTINUED: Reassurance and risk reduction

Ms. F’s psychiatrist reassures her that she does not have AD. She receives genetic counseling and decides to forgo genetic testing. Her psychiatrist educates Ms. F about the risks of OTC supplements—especially increased risk of bleeding because she takes aspirin and clopidogrel—and lack of data supporting their use. Ms. F is counseled that a healthy lifestyle, including regular exercise, Mediterranean diet with increased intake of omega-3 fatty acids, learning new things, and being socially active, is the safest way to promote brain health. Over 3 months, Ms. F discontinues all supplements except the vitamins and omega-3, starts exercising, resumes piano lessons that she stopped 10 years ago, and becomes a vegetarian. She continues to have mild SCI but she says she is not bothered by it and feels satisfied that she is doing all she can to promote her brain health.

Related Resources

• Desai AK. Healthy brain aging: evidence based methods to preserve brain function and prevent dementia. Philadelphia, PA: W. B. Saunders; 2010.
• Doidge N. The brain that changes itself. New York, NY: Penguin Books; 2007.
• Vance DE, Roberson AJ, McGuinness TM, et al. How neuroplasticity and cognitive reserve protect cognitive functioning. J Psychosoc Nurs Ment Health Serv. 2010; 48: 1-8.

Brain Training Resources

• Weil A, Small G. The healthy brain kit. Boulder, CO: Sounds True, Inc.; 2007. Audio CDs, brain-training cards and workbooks.
• Posit Science. www.positscience.com.
• Sharp Brains. www.sharpbrains.com.

Drug Brand Names

• Atenolol • Tenormin
• Atorvastatin • Lipitor
• Clopidogrel • Plavix
• Levothyroxine • Levoxyl, Synthroid

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Featured Audio

Abhilash K. Desai, MD, discusses emerging research on biomarkers that may help clarify diagnosis.

MS. F, age 66, requests genetic testing because she is concerned about mild memory difficulties, such as forgetting names and where she puts her keys or checkbook, and fears she may be developing Alzheimer’s disease (AD). Her mother and sister were diagnosed with AD in their early 60s. Ms. F has 20 years of education and reports no problems with driving, managing her finances, remembering to take her medications, or maintaining social activities, which her husband confirms.

Detailed questioning about anxiety and depressive symptoms reveals substantial worries about future cognitive decline and some concerns about her finances and her husband’s health. Ms. F says she occasionally feels down and has low energy but denies other depressive symptoms. She reports no sleep disturbances—including snoring and daytime sleepiness, which could indicate obstructive sleep apnea—which her husband confirms. Ms. F takes levothyroxine for hypothyroidism, atenolol for hypertension, aspirin and clopidogrel for coronary artery disease, and atorvastatin for hyperlipidemia. In addition, she provides a long list of over-the-counter (OTC) supplements—ginkgo, huperzine, ginseng, phosphatidylserine, B1, B12, folate, vitamin D, alpha-lipoic acid, and vinpocetine—that she takes to “protect” her brain from AD.

Subjective cognitive impairment (SCI) in older persons is a common condition with a largely unclear prognosis. Many older adults (age ≥65) express concern about mild cognitive problems—“senior moments”—such as word-finding difficulties and forgetfulness.¹ Individuals may wonder if walking into a room only to forget why might be the first sign of dementia. Some older adults try to counteract these memory problems by engaging in brain exercises—including costly computer games—and taking OTC “brain-enhancing” vitamins, herbal remedies, and other supplements.

Although some clinicians may view SCI as benign, that is not always true (Table l).^2-5 This article discusses the clinical significance of these mild cognitive complaints by examining:

• age-related cognitive decline (ARCD)
• SCI
• how SCI can be differentiated from more serious conditions, such as mild cognitive impairment (MCI) and early stages of AD and other dementias.

We also will discuss assessing and treating cognitive complaints. Although distinctions between SCI and ARCD may be controversial, evidence suggests clinicians need to adopt a more nuanced clinical approach.

Table 1

Why SCI should be taken seriously

‘Normal’ cognitive decline

ARCD is subtle decline in cognitive abilities, such as episodic memory, attention, and time needed to complete complex activities.^6,7 Individuals with ARCD might not have subjective memory complaints or objective cognitive deficits, and their ability to live independently may not be compromised.⁷ The degree of decline in ARCD may be smaller than previously thought.⁸ Park⁹ summarizes 4 main mechanisms thought to underlie age-related declines in cognition:

• reduced speed of processing
• decreased working memory capabilities
• declining inhibitory control (eg, impaired complex attentional capabilities)
• sensory changes (eg, visual and auditory deficits).

ARCD traditionally is thought to result from predictable changes in the brain associated with aging, such as reduced brain volume in the hippocampus and frontal lobes, loss of myelin, loss of synapses, and cytoskeletal changes.⁷ However, not all older adults experience ARCD. Some remain highly functional in their later years and continue to actively engage in life well into very old age.^6,9

Subjective cognitive impairment

One-quarter to one-half of community-dwelling older adults report subjective cognitive complaints, such as forgetfulness and word-finding difficulties.¹⁰ Patients with SCI do not show objective evidence of cognitive impairment on neuropsychological tests and their cognitive problems cause no functional decline.¹⁰

Preliminary evidence indicates that SCI may be a harbinger of further cognitive decline. Reisberg et al³ found that compared with patients without SCI, patients with SCI were 4.5 times more likely to develop MCI—cognitive difficulties that can be detected by cognitive tests, but do not cause functional decline—or dementia within 7 years.³ Studies also have suggested that SCI may be a pre-MCI stage of subsequent dementia.^11-13 AD generally has a long (10 to 12 years) and progressive prodromal phase before dementia onset and is characterized by successive emergence of cognitive deficits, memory complaints, depressive symptoms, and functional impairment.¹⁴

In light of this research, we believe patients with SCI and other risk factors for AD, such as a family history of AD, may be at higher risk of further cognitive and functional decline compared with individuals with ARCD and no AD risk factors. Therefore, patients with SCI and other risk factors for AD (Table 2)^15-19 may benefit from annual follow-up to determine if cognitive problems have progressed to MCI or AD.

SCI may be a response to subclinical alterations in neurobiology—a phenomenon known as reverse causality.²⁰ Biomarkers, such as cerebrospinal fluid levels of ß-amyloid and phosphorylated tau, and amyloid imaging using positron emission tomography may help identify AD in SCI patients.²¹ In these patients, SCI is a misnomer because the cognitive impairment is real—not “subjective”—but current tests are not sensitive enough to detect the cognitive decline the patient has recognized. This group of patients should be differentiated from individuals who may perceive typical cognitive aging (ARCD) as pathologic and complain about it. In the future, biomarkers may help differentiate these 2 groups.

Table 2

Factors that increase SCI patients’ risk for dementia

Mild cognitive impairment

MCI is similar to SCI because MCI patients may present with complaints of memory decline and other cognitive difficulties²² but neither condition is associated with significant impairment of daily activities.²³ The key difference is that patients with MCI demonstrate impaired performance on objective cognitive tests whereas SCI patients do not.²⁴ In our experience, office-based tests do not reliably differentiate the 2 conditions because many patients with SCI may show mild impairment in tests such as the Mini-Mental State Exam (MMSE)²⁵ but comprehensive neuropsychological testing reveals no objective cognitive deficits. Neuropsychological testing is essential to reliably differentiate SCI from MCI.

The distinction between SCI and MCI is clinically relevant because evidence suggests that MCI patients have a near-term risk of developing dementia, particularly AD.^22,23 In a longitudinal study of 76 individuals with MCI, 12% of patients progressed to AD each year compared with 1% to 2% of healthy older adults.²⁶ Patients with MCI are at increased risk of delirium (especially during hospitalization), falls, medication errors, and difficulty managing their finances.²⁴ Older adults with MCI also have increased mortality compared with older adults with normal cognitive functioning.²² Both SCI and MCI should be differentiated from mild dementia. Common dementias in older adults include:

• AD dementia
• Vascular dementia (may occur with or without AD)
• Lewy body dementia
• Frontotemporal dementia
• Parkinson’s disease dementia.

By definition, all dementia types are associated with impaired ability to perform daily activities and cognitive decline.²⁷

Assessing cognitive complaints

Evaluation of older adults’ cognitive complaints should begin with a thorough history to elicit symptoms of anxiety, depression, physical complaints, and any associated functional decline; a physical exam; and a comprehensive mental status examination. This initial evaluation should be followed by routine and specific investigations as indicated (Table 3).^22,24,28,29

In a 6-year study of 100 older adults with and without objective evidence of memory decline, both groups showed similar rates of cognitive complaints.³⁰ Also, researchers found no relationship between individuals’ perception of their cognitive functioning and performance on neuropsychological testing. Mood, education level, and apolipoprotein E epsilon 4 genotype status also did not correlate with participants’ subjective cognitive complaints. These findings highlight the need for objective test data to determine whether older adults’ memory complaints reflect pathologic changes in cognition. After a thorough diagnostic workup, some patients complaining of memory decline will have no detectable evidence of cognitive dysfunction or an identifiable cause. However, others may have identifiable causes of memory impairment (Table 4)^28,29,31,32—which could be treated—some will have MCI, and others may be in an early stage of dementia.

Table 3

Investigation of older adults with SCI

Table 4

Differential diagnosis of SCI

CASE CONTINUED: No measurable deficits

Ms. F’s medical history is remarkable for coronary artery disease, hypothyroidism, hypertension, hyperlipidemia, cataracts, arthritis, back surgery (secondary to spondylosis), and foot surgery. Ms. F denies a history of alcohol or illicit substance abuse. She smoked tobacco for 30 years (2 packs per day), but quit 5 years ago after her heart attack. Physical exam is unremarkable except for mild obesity (body mass index = 31 kg/m²).

Ms. F’s mental status exam reveals anxious mood and affect. Her recall is 2 out of 3 items. Her MMSE score is 29/30 (1 point lost on recall) and her Geriatric Depression Scale³³ score is 2/15, indicating minimal depressive symptoms. On neuropsychological testing, Ms. F demonstrates high average intellectual abilities; compared with others her age, she performs within expectations on all measures. That is, she performs within the above-average to low-average range on measures of attention, working memory, speed of processing, expressive language, learning, memory, visual spatial abilities, executive functioning, and knowledge of basic health and safety information.

Enhancing neuroplasticity

We recommend neuroplasticity-based interventions to treat SCI and promote healthy brain aging.^20,29 For a checklist clinicians can use to promote healthy brain aging and thus improve patients’ cognitive health see this article at CurrentPsychiatry. com. Table 5^1,29 lists cognitive strategies to improve memory and maintain cognitive vitality.

Enhancing brain plasticity and neurogenesis requires engaging older adults in demanding sensory, cognitive, and motor activities on an intensive basis.³⁴ Therapeutic stimulation of neuroplasticity and neurogenesis might contribute to functional “repair” of the diseased adult brain before damage to whole neuronal networks has ensued.²⁹ An important treatment component is reassuring patients with SCI that they do not have AD or MCI. Treating comorbid anxiety and depression and reversible causes of cognitive complaints is key to successful outcomes.

Table 5

Strategies to improve memory and maintain cognitive vitality

CASE CONTINUED: Reassurance and risk reduction

Ms. F’s psychiatrist reassures her that she does not have AD. She receives genetic counseling and decides to forgo genetic testing. Her psychiatrist educates Ms. F about the risks of OTC supplements—especially increased risk of bleeding because she takes aspirin and clopidogrel—and lack of data supporting their use. Ms. F is counseled that a healthy lifestyle, including regular exercise, Mediterranean diet with increased intake of omega-3 fatty acids, learning new things, and being socially active, is the safest way to promote brain health. Over 3 months, Ms. F discontinues all supplements except the vitamins and omega-3, starts exercising, resumes piano lessons that she stopped 10 years ago, and becomes a vegetarian. She continues to have mild SCI but she says she is not bothered by it and feels satisfied that she is doing all she can to promote her brain health.

Related Resources

• Desai AK. Healthy brain aging: evidence based methods to preserve brain function and prevent dementia. Philadelphia, PA: W. B. Saunders; 2010.
• Doidge N. The brain that changes itself. New York, NY: Penguin Books; 2007.
• Vance DE, Roberson AJ, McGuinness TM, et al. How neuroplasticity and cognitive reserve protect cognitive functioning. J Psychosoc Nurs Ment Health Serv. 2010; 48: 1-8.

Brain Training Resources

• Weil A, Small G. The healthy brain kit. Boulder, CO: Sounds True, Inc.; 2007. Audio CDs, brain-training cards and workbooks.
• Posit Science. www.positscience.com.
• Sharp Brains. www.sharpbrains.com.

Drug Brand Names

• Atenolol • Tenormin
• Atorvastatin • Lipitor
• Clopidogrel • Plavix
• Levothyroxine • Levoxyl, Synthroid

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Featured Audio

Abhilash K. Desai, MD, discusses emerging research on biomarkers that may help clarify diagnosis.

MS. F, age 66, requests genetic testing because she is concerned about mild memory difficulties, such as forgetting names and where she puts her keys or checkbook, and fears she may be developing Alzheimer’s disease (AD). Her mother and sister were diagnosed with AD in their early 60s. Ms. F has 20 years of education and reports no problems with driving, managing her finances, remembering to take her medications, or maintaining social activities, which her husband confirms.

Detailed questioning about anxiety and depressive symptoms reveals substantial worries about future cognitive decline and some concerns about her finances and her husband’s health. Ms. F says she occasionally feels down and has low energy but denies other depressive symptoms. She reports no sleep disturbances—including snoring and daytime sleepiness, which could indicate obstructive sleep apnea—which her husband confirms. Ms. F takes levothyroxine for hypothyroidism, atenolol for hypertension, aspirin and clopidogrel for coronary artery disease, and atorvastatin for hyperlipidemia. In addition, she provides a long list of over-the-counter (OTC) supplements—ginkgo, huperzine, ginseng, phosphatidylserine, B1, B12, folate, vitamin D, alpha-lipoic acid, and vinpocetine—that she takes to “protect” her brain from AD.

Subjective cognitive impairment (SCI) in older persons is a common condition with a largely unclear prognosis. Many older adults (age ≥65) express concern about mild cognitive problems—“senior moments”—such as word-finding difficulties and forgetfulness.¹ Individuals may wonder if walking into a room only to forget why might be the first sign of dementia. Some older adults try to counteract these memory problems by engaging in brain exercises—including costly computer games—and taking OTC “brain-enhancing” vitamins, herbal remedies, and other supplements.

Although some clinicians may view SCI as benign, that is not always true (Table l).^2-5 This article discusses the clinical significance of these mild cognitive complaints by examining:

• age-related cognitive decline (ARCD)
• SCI
• how SCI can be differentiated from more serious conditions, such as mild cognitive impairment (MCI) and early stages of AD and other dementias.

We also will discuss assessing and treating cognitive complaints. Although distinctions between SCI and ARCD may be controversial, evidence suggests clinicians need to adopt a more nuanced clinical approach.

Table 1

Why SCI should be taken seriously

‘Normal’ cognitive decline

ARCD is subtle decline in cognitive abilities, such as episodic memory, attention, and time needed to complete complex activities.^6,7 Individuals with ARCD might not have subjective memory complaints or objective cognitive deficits, and their ability to live independently may not be compromised.⁷ The degree of decline in ARCD may be smaller than previously thought.⁸ Park⁹ summarizes 4 main mechanisms thought to underlie age-related declines in cognition:

• reduced speed of processing
• decreased working memory capabilities
• declining inhibitory control (eg, impaired complex attentional capabilities)
• sensory changes (eg, visual and auditory deficits).

ARCD traditionally is thought to result from predictable changes in the brain associated with aging, such as reduced brain volume in the hippocampus and frontal lobes, loss of myelin, loss of synapses, and cytoskeletal changes.⁷ However, not all older adults experience ARCD. Some remain highly functional in their later years and continue to actively engage in life well into very old age.^6,9

Subjective cognitive impairment

One-quarter to one-half of community-dwelling older adults report subjective cognitive complaints, such as forgetfulness and word-finding difficulties.¹⁰ Patients with SCI do not show objective evidence of cognitive impairment on neuropsychological tests and their cognitive problems cause no functional decline.¹⁰

Preliminary evidence indicates that SCI may be a harbinger of further cognitive decline. Reisberg et al³ found that compared with patients without SCI, patients with SCI were 4.5 times more likely to develop MCI—cognitive difficulties that can be detected by cognitive tests, but do not cause functional decline—or dementia within 7 years.³ Studies also have suggested that SCI may be a pre-MCI stage of subsequent dementia.^11-13 AD generally has a long (10 to 12 years) and progressive prodromal phase before dementia onset and is characterized by successive emergence of cognitive deficits, memory complaints, depressive symptoms, and functional impairment.¹⁴

In light of this research, we believe patients with SCI and other risk factors for AD, such as a family history of AD, may be at higher risk of further cognitive and functional decline compared with individuals with ARCD and no AD risk factors. Therefore, patients with SCI and other risk factors for AD (Table 2)^15-19 may benefit from annual follow-up to determine if cognitive problems have progressed to MCI or AD.

SCI may be a response to subclinical alterations in neurobiology—a phenomenon known as reverse causality.²⁰ Biomarkers, such as cerebrospinal fluid levels of ß-amyloid and phosphorylated tau, and amyloid imaging using positron emission tomography may help identify AD in SCI patients.²¹ In these patients, SCI is a misnomer because the cognitive impairment is real—not “subjective”—but current tests are not sensitive enough to detect the cognitive decline the patient has recognized. This group of patients should be differentiated from individuals who may perceive typical cognitive aging (ARCD) as pathologic and complain about it. In the future, biomarkers may help differentiate these 2 groups.

Table 2

Factors that increase SCI patients’ risk for dementia

Mild cognitive impairment

MCI is similar to SCI because MCI patients may present with complaints of memory decline and other cognitive difficulties²² but neither condition is associated with significant impairment of daily activities.²³ The key difference is that patients with MCI demonstrate impaired performance on objective cognitive tests whereas SCI patients do not.²⁴ In our experience, office-based tests do not reliably differentiate the 2 conditions because many patients with SCI may show mild impairment in tests such as the Mini-Mental State Exam (MMSE)²⁵ but comprehensive neuropsychological testing reveals no objective cognitive deficits. Neuropsychological testing is essential to reliably differentiate SCI from MCI.

The distinction between SCI and MCI is clinically relevant because evidence suggests that MCI patients have a near-term risk of developing dementia, particularly AD.^22,23 In a longitudinal study of 76 individuals with MCI, 12% of patients progressed to AD each year compared with 1% to 2% of healthy older adults.²⁶ Patients with MCI are at increased risk of delirium (especially during hospitalization), falls, medication errors, and difficulty managing their finances.²⁴ Older adults with MCI also have increased mortality compared with older adults with normal cognitive functioning.²² Both SCI and MCI should be differentiated from mild dementia. Common dementias in older adults include:

• AD dementia
• Vascular dementia (may occur with or without AD)
• Lewy body dementia
• Frontotemporal dementia
• Parkinson’s disease dementia.

By definition, all dementia types are associated with impaired ability to perform daily activities and cognitive decline.²⁷

Assessing cognitive complaints

Evaluation of older adults’ cognitive complaints should begin with a thorough history to elicit symptoms of anxiety, depression, physical complaints, and any associated functional decline; a physical exam; and a comprehensive mental status examination. This initial evaluation should be followed by routine and specific investigations as indicated (Table 3).^22,24,28,29

In a 6-year study of 100 older adults with and without objective evidence of memory decline, both groups showed similar rates of cognitive complaints.³⁰ Also, researchers found no relationship between individuals’ perception of their cognitive functioning and performance on neuropsychological testing. Mood, education level, and apolipoprotein E epsilon 4 genotype status also did not correlate with participants’ subjective cognitive complaints. These findings highlight the need for objective test data to determine whether older adults’ memory complaints reflect pathologic changes in cognition. After a thorough diagnostic workup, some patients complaining of memory decline will have no detectable evidence of cognitive dysfunction or an identifiable cause. However, others may have identifiable causes of memory impairment (Table 4)^28,29,31,32—which could be treated—some will have MCI, and others may be in an early stage of dementia.

Table 3

Investigation of older adults with SCI

Table 4

Differential diagnosis of SCI

CASE CONTINUED: No measurable deficits

Ms. F’s medical history is remarkable for coronary artery disease, hypothyroidism, hypertension, hyperlipidemia, cataracts, arthritis, back surgery (secondary to spondylosis), and foot surgery. Ms. F denies a history of alcohol or illicit substance abuse. She smoked tobacco for 30 years (2 packs per day), but quit 5 years ago after her heart attack. Physical exam is unremarkable except for mild obesity (body mass index = 31 kg/m²).

Ms. F’s mental status exam reveals anxious mood and affect. Her recall is 2 out of 3 items. Her MMSE score is 29/30 (1 point lost on recall) and her Geriatric Depression Scale³³ score is 2/15, indicating minimal depressive symptoms. On neuropsychological testing, Ms. F demonstrates high average intellectual abilities; compared with others her age, she performs within expectations on all measures. That is, she performs within the above-average to low-average range on measures of attention, working memory, speed of processing, expressive language, learning, memory, visual spatial abilities, executive functioning, and knowledge of basic health and safety information.

Enhancing neuroplasticity

We recommend neuroplasticity-based interventions to treat SCI and promote healthy brain aging.^20,29 For a checklist clinicians can use to promote healthy brain aging and thus improve patients’ cognitive health see this article at CurrentPsychiatry. com. Table 5^1,29 lists cognitive strategies to improve memory and maintain cognitive vitality.

Enhancing brain plasticity and neurogenesis requires engaging older adults in demanding sensory, cognitive, and motor activities on an intensive basis.³⁴ Therapeutic stimulation of neuroplasticity and neurogenesis might contribute to functional “repair” of the diseased adult brain before damage to whole neuronal networks has ensued.²⁹ An important treatment component is reassuring patients with SCI that they do not have AD or MCI. Treating comorbid anxiety and depression and reversible causes of cognitive complaints is key to successful outcomes.

Table 5

Strategies to improve memory and maintain cognitive vitality

CASE CONTINUED: Reassurance and risk reduction

Ms. F’s psychiatrist reassures her that she does not have AD. She receives genetic counseling and decides to forgo genetic testing. Her psychiatrist educates Ms. F about the risks of OTC supplements—especially increased risk of bleeding because she takes aspirin and clopidogrel—and lack of data supporting their use. Ms. F is counseled that a healthy lifestyle, including regular exercise, Mediterranean diet with increased intake of omega-3 fatty acids, learning new things, and being socially active, is the safest way to promote brain health. Over 3 months, Ms. F discontinues all supplements except the vitamins and omega-3, starts exercising, resumes piano lessons that she stopped 10 years ago, and becomes a vegetarian. She continues to have mild SCI but she says she is not bothered by it and feels satisfied that she is doing all she can to promote her brain health.

Related Resources

• Desai AK. Healthy brain aging: evidence based methods to preserve brain function and prevent dementia. Philadelphia, PA: W. B. Saunders; 2010.
• Doidge N. The brain that changes itself. New York, NY: Penguin Books; 2007.
• Vance DE, Roberson AJ, McGuinness TM, et al. How neuroplasticity and cognitive reserve protect cognitive functioning. J Psychosoc Nurs Ment Health Serv. 2010; 48: 1-8.

Brain Training Resources

• Weil A, Small G. The healthy brain kit. Boulder, CO: Sounds True, Inc.; 2007. Audio CDs, brain-training cards and workbooks.
• Posit Science. www.positscience.com.
• Sharp Brains. www.sharpbrains.com.

Drug Brand Names

• Atenolol • Tenormin
• Atorvastatin • Lipitor
• Clopidogrel • Plavix
• Levothyroxine • Levoxyl, Synthroid

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Featured Audio

Abhilash K. Desai, MD, discusses emerging research on biomarkers that may help clarify diagnosis.