Imaging

MUNICH — A new type of cardiac pacemaker was safe in patients undergoing an MRI examination, with no need for a special imaging protocol in a randomized study with 151 evaluable patients.

“The functionality of the new pacemaker is the same as a conventional pacemaker, but one is MRI safe and the other is not,” Dr. Torsten Sommer said at the annual congress of the European Society of Cardiology. There is no apparent downside to the new pacemaker, except that it may cost more than current units do, he said.

Patients with a standard pacemaker face “a huge limitation” by not being able to easily undergo MRI imaging, which has become a practice staple, said Dr. Sommer, chief of the cardiovascular imaging section at the University of Bonn (Germany). He estimated that an average pacemaker patient today has a 50%–75% lifetime chance of needing at least one MRI exam.

The major danger that MRI poses to a patient with a conventional pacemaker (or other implanted cardiac device) is heating of the lead tips by radiofrequency radiation. Other concerns are interference with pacemaker function and risk of an electrical reset of the device.

A special MRI protocol has been reported that avoids these problems, but the method is complicated and available only at a limited number of experienced imaging centers, commented Dr. Christopher Cannon, a cardiologist at Brigham and Women's Hospital and Harvard Medical School, Boston. Having a new pacemaker without the MRI limitation would be “very helpful,” he said in an interview.

The new pacemaker, called EnRhythm, was developed by Medtronic Inc., which funded the current study. Dr. Sommer is a consultant to Medtronic, but he and his associates in Bonn do not hold any patents on the new device or technology. The data he reported came from the first phase of a study designed to eventually place the new pacemaker in 470 patients. When the final results are available, Medtronic will apply for marketing approval from the Food and Drug Administration, a step that the company hopes to take in 2010, said Tracy McNulty, a Medtronic spokeswoman.

The new, dual-chamber pacemaker features a reduced number of ferromagnetic parts, better protection of internal circuits, and altered software. But the implantation technique is the same as for a standard pacemaker, Dr. Sommer said.

The study is being done at 53 centers in the United States, Canada, and Europe. So far, 245 patients with a class I or II indication for a pacemaker have been implanted with the EnRhythm device. Ninety patients were randomized to undergo MRI imaging and 101 were randomized as controls who received no imaging.

The MRI exam was done on a 1.5-T unit and involved 15 clinically relevant head- and lumbar spine-imaging sequences. To maximize safety during the first phase of testing, no magnetic coils were placed directly above a spinal region that extended from the C1 to the T12 level. But even with this limitation, full imaging of the chest region was obtained, Dr. Sommer said.

Follow-up data collected 1 month after the MRI exam were available for 70 patients and for 81 of the matched controls. The results showed no adverse events or complications triggered by the MRI exam, and no electrical resets of the pacemakers. During follow-up, no patients had sustained arrhythmias and the pacemakers did not show any changes in their rhythm-capture thresholds or any other performance changes.

'The functionality … is the same as a conventional pacemaker, but one is MRI safe and the other is not.' DR. SOMMER

MUNICH — A new type of cardiac pacemaker was safe in patients undergoing an MRI examination, with no need for a special imaging protocol in a randomized study with 151 evaluable patients.

“The functionality of the new pacemaker is the same as a conventional pacemaker, but one is MRI safe and the other is not,” Dr. Torsten Sommer said at the annual congress of the European Society of Cardiology. There is no apparent downside to the new pacemaker, except that it may cost more than current units do, he said.

Patients with a standard pacemaker face “a huge limitation” by not being able to easily undergo MRI imaging, which has become a practice staple, said Dr. Sommer, chief of the cardiovascular imaging section at the University of Bonn (Germany). He estimated that an average pacemaker patient today has a 50%–75% lifetime chance of needing at least one MRI exam.

The major danger that MRI poses to a patient with a conventional pacemaker (or other implanted cardiac device) is heating of the lead tips by radiofrequency radiation. Other concerns are interference with pacemaker function and risk of an electrical reset of the device.

A special MRI protocol has been reported that avoids these problems, but the method is complicated and available only at a limited number of experienced imaging centers, commented Dr. Christopher Cannon, a cardiologist at Brigham and Women's Hospital and Harvard Medical School, Boston. Having a new pacemaker without the MRI limitation would be “very helpful,” he said in an interview.

The new pacemaker, called EnRhythm, was developed by Medtronic Inc., which funded the current study. Dr. Sommer is a consultant to Medtronic, but he and his associates in Bonn do not hold any patents on the new device or technology. The data he reported came from the first phase of a study designed to eventually place the new pacemaker in 470 patients. When the final results are available, Medtronic will apply for marketing approval from the Food and Drug Administration, a step that the company hopes to take in 2010, said Tracy McNulty, a Medtronic spokeswoman.

The new, dual-chamber pacemaker features a reduced number of ferromagnetic parts, better protection of internal circuits, and altered software. But the implantation technique is the same as for a standard pacemaker, Dr. Sommer said.

The study is being done at 53 centers in the United States, Canada, and Europe. So far, 245 patients with a class I or II indication for a pacemaker have been implanted with the EnRhythm device. Ninety patients were randomized to undergo MRI imaging and 101 were randomized as controls who received no imaging.

The MRI exam was done on a 1.5-T unit and involved 15 clinically relevant head- and lumbar spine-imaging sequences. To maximize safety during the first phase of testing, no magnetic coils were placed directly above a spinal region that extended from the C1 to the T12 level. But even with this limitation, full imaging of the chest region was obtained, Dr. Sommer said.

Follow-up data collected 1 month after the MRI exam were available for 70 patients and for 81 of the matched controls. The results showed no adverse events or complications triggered by the MRI exam, and no electrical resets of the pacemakers. During follow-up, no patients had sustained arrhythmias and the pacemakers did not show any changes in their rhythm-capture thresholds or any other performance changes.

'The functionality … is the same as a conventional pacemaker, but one is MRI safe and the other is not.' DR. SOMMER

MUNICH — A new type of cardiac pacemaker was safe in patients undergoing an MRI examination, with no need for a special imaging protocol in a randomized study with 151 evaluable patients.

“The functionality of the new pacemaker is the same as a conventional pacemaker, but one is MRI safe and the other is not,” Dr. Torsten Sommer said at the annual congress of the European Society of Cardiology. There is no apparent downside to the new pacemaker, except that it may cost more than current units do, he said.

Patients with a standard pacemaker face “a huge limitation” by not being able to easily undergo MRI imaging, which has become a practice staple, said Dr. Sommer, chief of the cardiovascular imaging section at the University of Bonn (Germany). He estimated that an average pacemaker patient today has a 50%–75% lifetime chance of needing at least one MRI exam.

The major danger that MRI poses to a patient with a conventional pacemaker (or other implanted cardiac device) is heating of the lead tips by radiofrequency radiation. Other concerns are interference with pacemaker function and risk of an electrical reset of the device.

A special MRI protocol has been reported that avoids these problems, but the method is complicated and available only at a limited number of experienced imaging centers, commented Dr. Christopher Cannon, a cardiologist at Brigham and Women's Hospital and Harvard Medical School, Boston. Having a new pacemaker without the MRI limitation would be “very helpful,” he said in an interview.

The new pacemaker, called EnRhythm, was developed by Medtronic Inc., which funded the current study. Dr. Sommer is a consultant to Medtronic, but he and his associates in Bonn do not hold any patents on the new device or technology. The data he reported came from the first phase of a study designed to eventually place the new pacemaker in 470 patients. When the final results are available, Medtronic will apply for marketing approval from the Food and Drug Administration, a step that the company hopes to take in 2010, said Tracy McNulty, a Medtronic spokeswoman.

The new, dual-chamber pacemaker features a reduced number of ferromagnetic parts, better protection of internal circuits, and altered software. But the implantation technique is the same as for a standard pacemaker, Dr. Sommer said.

The study is being done at 53 centers in the United States, Canada, and Europe. So far, 245 patients with a class I or II indication for a pacemaker have been implanted with the EnRhythm device. Ninety patients were randomized to undergo MRI imaging and 101 were randomized as controls who received no imaging.

The MRI exam was done on a 1.5-T unit and involved 15 clinically relevant head- and lumbar spine-imaging sequences. To maximize safety during the first phase of testing, no magnetic coils were placed directly above a spinal region that extended from the C1 to the T12 level. But even with this limitation, full imaging of the chest region was obtained, Dr. Sommer said.

Follow-up data collected 1 month after the MRI exam were available for 70 patients and for 81 of the matched controls. The results showed no adverse events or complications triggered by the MRI exam, and no electrical resets of the pacemakers. During follow-up, no patients had sustained arrhythmias and the pacemakers did not show any changes in their rhythm-capture thresholds or any other performance changes.

'The functionality … is the same as a conventional pacemaker, but one is MRI safe and the other is not.' DR. SOMMER

Many patients with spinal arachnoid cysts complain of symptoms suggesting spinal cord compression, and are often initially evaluated by their primary physicians. However, these cysts are often discovered incidentally.

This article discusses how to manage spinal arachnoid cysts, whether found incidentally or during an evaluation for symptoms of spinal cord compression.

PRESENTATIONS CAN VARY WIDELY

A patient with a clinically relevant spinal arachnoid cyst is most likely to be a boy in his teens, but these cysts can occur in either sex and have been reported in patients as young as a few months and as old as nearly 80 years.^1–6

In their typical presentation, spinal arachnoid cysts cause progressive signs and symptoms suggesting spinal cord compression. But because a cyst can occur at any spinal level and in a patient of any age, no one clinical presentation is pathognomonic, and the clinical sequelae can differ drastically from patient to patient. Nevertheless, we can make certain generalizations: a spinal arachnoid cyst that compresses the spinal cord typically causes waxing and waning pain and progressive spastic or flaccid paraparesis, which often are exacerbated by Valsalva maneuvers.^1,6 Spinal arachnoid cysts can also present with symptoms suggestive of an isolated radiculopathy.

Less typical presentations include noncardiac chest pain, isolated gait difficulty, and isolated urinary urgency.^2–4

Missed diagnosis is common

Because the symptoms are so variable and nonspecific, the diagnosis of spinal arachnoid cysts is often missed. For example, a sacral extradural arachnoid cyst can cause pain in the low back and perineal region, which is often relieved by lying flat and aggravated by Valsalva maneuvers.⁷

Complicating the picture, spinal arachnoid cysts can also coexist with other disorders of the central nervous system. Cases have been reported of sacral extradural arachnoid cysts coexisting with lumbar disk prolapse⁷ and of spinal arachnoid cysts located near a syrinx (a tube-shaped cavity in the spinal cord).^3,8 A patient can have more than one spinal arachnoid cyst, or both a spinal arachnoid cyst and a concurrent intracranial arachnoid cyst or a tumor.⁹

EXTRADURAL VS INTRADURAL CYSTS

Like other types of spinal meningeal cysts, spinal arachnoid cysts can be broadly characterized as either extradural or intradural.¹⁰

Extradural cysts are extradural outpouchings of arachnoid that are contiguous with the spinal subarachnoid space via a small dural defect. They typically occur in the thoracic spine dorsal to the spinal cord, although they may be found elsewhere.

Intradural cysts are outpouchings of arachnoid that, regardless of size, lie entirely within the dural space. Intradural arachnoid cysts are more common than extradural cysts.

Either type of cyst may or may not communicate with the subarachnoid space.^1–3

Other cystic lesions of the spine exist. One of the most common is the Tarlov cyst, which may look similar to a spinal arachnoid cyst, as both types of cysts are collections of cerebrospinal fluid. But, unlike typical spinal arachnoid cysts, Tarlov cysts occur only in the sacral spine and appear solely within the sacral root on radiographic imaging.

HOW DO CYSTS FORM?

How spinal arachnoid cysts start to form is open to conjecture, and several theories exist.^1,2,7 They are often attributed to congenital defects. Another possibility is that arachnoid adhesions develop secondary to inflammation, which may arise from infection (meningitis), hemorrhage, or an iatrogenic cause such as injected contrast media or anesthetics or from the intraoperative contaminants of fibrin glue.¹¹ Some cysts are due to trauma from lumbar puncture, anesthetic procedures, or intradural surgery. Other cysts are idiopathic.

WHY DO CYSTS ENLARGE?

Several mechanisms have been proposed to explain why spinal arachnoid cysts enlarge.² The cells in the cyst wall probably do not secrete fluid: many spinal arachnoid cyst walls are composed primarily of simple connective tissue, and many completely lack an inner arachnoid lining—the cells that normally secrete spinal fluid—or have only a sparse lining.⁶ A unidirectional “valve” might let fluid in but not out. Another mechanism is pathologic distribution of arachnoid trabeculae, leading to fluid shifts within the cyst, thereby causing an increase in size.

DIAGNOSIS IS OFTEN INCIDENTAL

Spinal arachnoid cysts are rare, so an algorithm to diagnose them solely on the basis of common presenting symptoms would be impractical.

Whenever an arachnoid cyst is discovered, one must determine whether the cyst—or another problem—is actually causing the symptoms. If treatment is to succeed, the clinical presentation must correspond to the radiographic findings. For example, removing a cervical arachnoid cyst is unlikely to relieve low back pain.

Although most arachnoid cysts are found by MRI, it is inappropriate to initially order MRI to evaluate a cyst’s common presenting symptoms (eg, back pain, radiculopathy).

Plain radiography should be done first. Although arachnoid cysts are composed of fluid and soft tissue, which are not easily detectable on plain films, subtle and indirect signs of a chronic, large cyst may be visible.⁵

MRI is the next step if plain radiographs do not reveal bony abnormalities that could explain a patient’s symptoms.

Further studies help characterize the lesion

Diffusion-weighted MRI can help differentiate an epidermoid cyst from an arachnoid cyst. It may also help differentiate a cyst from an abscess or tumor: abscesses have areas of restricted diffusion, and tumors tend to lack cerebrospinal fluid signal in their central core. Diffusion-weighted MRI can also help evaluate spinal cord atrophy and inflammatory changes.^1,6,12 If an arachnoid cyst accompanies a nerve root as it enters the neural foramen, this would also appear on MRI.

Myelography or computed tomographic (CT) myelography were used to further characterize the form and structure of spinal arachnoid cysts discovered on MRI in most reported cases, and most authors advocate these studies.^1,3,8,12 Specifically, CT myelography has been used to look for a communication between the intraspinal subarachnoid space and the spinal arachnoid cyst, and it is sensitive in determining whether a communication exists, although it does not pinpoint the location of the communication very well.¹² CT myelography is also invaluable for imaging the spine of patients who have contraindications to MRI.

Kinematic MRI (cine-MRI) is now widely available and can help evaluate for the presence of communications between the cyst and the subarachnoid space. Dural defects may be located by carefully scrutinizing cine-MRI images for pulsating turbulent flow voids, facilitating a more focused and minimally invasive treatment strategy.¹³

Neo et al¹² used cine-MRI to evaluate and plan the surgical resection of a giant spinal extradural arachnoid cyst. MRI helped determine the initial diagnosis, and a pulsating turbulent flow void was observed by cine-MRI in the area later confirmed surgically to contain the communication between the cyst and the spinal subarachnoid space.

Cine-MRI is not necessary as part of the initial diagnostic evaluation for spinal arachnoid cysts. It is of particular value only to the surgeon, who can request it if needed.

HISTOPATHOLOGY

With hematoxylin and eosin staining, the walls of spinal arachnoid cysts are typically seen as fibrous and lined by meningothelial cells.

TREATMENT

Observe asymptomatic cysts

For incidentally discovered spinal arachnoid cysts that cause no symptoms—ie, most of them—surgery is not recommended. No correlation exists between the size of a cyst and the need for treatment. Yearly imaging should be done to detect any new abnormality and determine whether the cyst is truly benign.

If symptoms arise, reevaluation of the cyst with MRI should be immediately undertaken.

Remove symptomatic cyst if possible

For a patient with symptoms, treatment offers an excellent chance of neurologic recovery.

Aspiration of the cyst is not routinely advised. Although aspiration may intuitively seem like the best initial approach to management, it only temporarily improves symptoms. However, percutaneous aspiration under fluoroscopic guidance may be appropriate for determining whether a cyst is causing a patient’s symptoms and thereby predicting whether surgery can help. Surgery should be undertaken only after careful consideration, as postoperative complications, though uncommon, may be very troublesome for both the patient and the surgeon.

Complete resection is ideal treatment. The standard treatment of an isolated spinal arachnoid cyst is complete surgical removal of the cyst.¹ Surgery typically results in excellent outcomes in terms of resolution of symptoms, and is effective across a large range of cyst sizes.

Drain cysts that cannot be resected. Unfortunately, not all isolated spinal arachnoid cysts can be fully resected, owing to their location or to intraoperative findings such as extensive adhesion of a cyst to the spinal cord. In such cases, fenestration of the cyst wall, percutaneous drainage, or shunting the cyst into the peritoneal cavity may relieve symptoms.^1–3,6

Minimally invasive surgical techniques have also met with some success. Neo et al¹² reported that they successfully treated a giant spinal extradural arachnoid cyst by selectively closing the dural defect with clips. Cine-MRI was used to pinpoint the communication, allowing for a focused, limited surgical approach requiring only fenestration. The dural surface of the cyst was examined with an operating microscope.

Endoscopic approaches have also been used to treat sacral extradural arachnoid cysts.⁷

SOME CASES ARE MORE COMPLEX

Managing spinal arachnoid cysts becomes more complex as cysts become more intricate in morphology and if multiple cysts exist across different vertebral levels. Surgical planning and intraoperative monitoring are also complicated if a spinal arachnoid cyst coexists with another central nervous system problem.

Cases have been reported of patients with coexisting spinal arachnoid cysts and lumbar disk herniation; in many, the latter problem was considered to be the cause of symptoms.⁷

Holly and Batzdorf³ described patients with both intradural arachnoid cysts and syringomyelia. Cysts were resected with the aid of an operating microscope, and intraoperative ultrasonography confirmed that normal pulsation of the subarachnoid cerebrospinal fluid had returned after resection. The syrinx cavities were not surgically manipulated, yet MRI taken 3 months after surgery revealed that they had significantly diminished in each case.

The best predictor of recovery in patients who undergo surgery for spinal arachnoid cysts is if the clinical presentation correlates with the defect.^1,7 Usually the postsurgical prognosis is good, with significant to full neurologic recovery in patients with all cyst types and clinical presentations.

Many patients with spinal arachnoid cysts complain of symptoms suggesting spinal cord compression, and are often initially evaluated by their primary physicians. However, these cysts are often discovered incidentally.

This article discusses how to manage spinal arachnoid cysts, whether found incidentally or during an evaluation for symptoms of spinal cord compression.

PRESENTATIONS CAN VARY WIDELY

A patient with a clinically relevant spinal arachnoid cyst is most likely to be a boy in his teens, but these cysts can occur in either sex and have been reported in patients as young as a few months and as old as nearly 80 years.^1–6

In their typical presentation, spinal arachnoid cysts cause progressive signs and symptoms suggesting spinal cord compression. But because a cyst can occur at any spinal level and in a patient of any age, no one clinical presentation is pathognomonic, and the clinical sequelae can differ drastically from patient to patient. Nevertheless, we can make certain generalizations: a spinal arachnoid cyst that compresses the spinal cord typically causes waxing and waning pain and progressive spastic or flaccid paraparesis, which often are exacerbated by Valsalva maneuvers.^1,6 Spinal arachnoid cysts can also present with symptoms suggestive of an isolated radiculopathy.

Less typical presentations include noncardiac chest pain, isolated gait difficulty, and isolated urinary urgency.^2–4

Missed diagnosis is common

Because the symptoms are so variable and nonspecific, the diagnosis of spinal arachnoid cysts is often missed. For example, a sacral extradural arachnoid cyst can cause pain in the low back and perineal region, which is often relieved by lying flat and aggravated by Valsalva maneuvers.⁷

Complicating the picture, spinal arachnoid cysts can also coexist with other disorders of the central nervous system. Cases have been reported of sacral extradural arachnoid cysts coexisting with lumbar disk prolapse⁷ and of spinal arachnoid cysts located near a syrinx (a tube-shaped cavity in the spinal cord).^3,8 A patient can have more than one spinal arachnoid cyst, or both a spinal arachnoid cyst and a concurrent intracranial arachnoid cyst or a tumor.⁹

EXTRADURAL VS INTRADURAL CYSTS

Like other types of spinal meningeal cysts, spinal arachnoid cysts can be broadly characterized as either extradural or intradural.¹⁰

Extradural cysts are extradural outpouchings of arachnoid that are contiguous with the spinal subarachnoid space via a small dural defect. They typically occur in the thoracic spine dorsal to the spinal cord, although they may be found elsewhere.

Intradural cysts are outpouchings of arachnoid that, regardless of size, lie entirely within the dural space. Intradural arachnoid cysts are more common than extradural cysts.

Either type of cyst may or may not communicate with the subarachnoid space.^1–3

Other cystic lesions of the spine exist. One of the most common is the Tarlov cyst, which may look similar to a spinal arachnoid cyst, as both types of cysts are collections of cerebrospinal fluid. But, unlike typical spinal arachnoid cysts, Tarlov cysts occur only in the sacral spine and appear solely within the sacral root on radiographic imaging.

HOW DO CYSTS FORM?

How spinal arachnoid cysts start to form is open to conjecture, and several theories exist.^1,2,7 They are often attributed to congenital defects. Another possibility is that arachnoid adhesions develop secondary to inflammation, which may arise from infection (meningitis), hemorrhage, or an iatrogenic cause such as injected contrast media or anesthetics or from the intraoperative contaminants of fibrin glue.¹¹ Some cysts are due to trauma from lumbar puncture, anesthetic procedures, or intradural surgery. Other cysts are idiopathic.

WHY DO CYSTS ENLARGE?

Several mechanisms have been proposed to explain why spinal arachnoid cysts enlarge.² The cells in the cyst wall probably do not secrete fluid: many spinal arachnoid cyst walls are composed primarily of simple connective tissue, and many completely lack an inner arachnoid lining—the cells that normally secrete spinal fluid—or have only a sparse lining.⁶ A unidirectional “valve” might let fluid in but not out. Another mechanism is pathologic distribution of arachnoid trabeculae, leading to fluid shifts within the cyst, thereby causing an increase in size.

DIAGNOSIS IS OFTEN INCIDENTAL

Spinal arachnoid cysts are rare, so an algorithm to diagnose them solely on the basis of common presenting symptoms would be impractical.

Whenever an arachnoid cyst is discovered, one must determine whether the cyst—or another problem—is actually causing the symptoms. If treatment is to succeed, the clinical presentation must correspond to the radiographic findings. For example, removing a cervical arachnoid cyst is unlikely to relieve low back pain.

Although most arachnoid cysts are found by MRI, it is inappropriate to initially order MRI to evaluate a cyst’s common presenting symptoms (eg, back pain, radiculopathy).

Plain radiography should be done first. Although arachnoid cysts are composed of fluid and soft tissue, which are not easily detectable on plain films, subtle and indirect signs of a chronic, large cyst may be visible.⁵

MRI is the next step if plain radiographs do not reveal bony abnormalities that could explain a patient’s symptoms.

Further studies help characterize the lesion

Diffusion-weighted MRI can help differentiate an epidermoid cyst from an arachnoid cyst. It may also help differentiate a cyst from an abscess or tumor: abscesses have areas of restricted diffusion, and tumors tend to lack cerebrospinal fluid signal in their central core. Diffusion-weighted MRI can also help evaluate spinal cord atrophy and inflammatory changes.^1,6,12 If an arachnoid cyst accompanies a nerve root as it enters the neural foramen, this would also appear on MRI.

Myelography or computed tomographic (CT) myelography were used to further characterize the form and structure of spinal arachnoid cysts discovered on MRI in most reported cases, and most authors advocate these studies.^1,3,8,12 Specifically, CT myelography has been used to look for a communication between the intraspinal subarachnoid space and the spinal arachnoid cyst, and it is sensitive in determining whether a communication exists, although it does not pinpoint the location of the communication very well.¹² CT myelography is also invaluable for imaging the spine of patients who have contraindications to MRI.

Kinematic MRI (cine-MRI) is now widely available and can help evaluate for the presence of communications between the cyst and the subarachnoid space. Dural defects may be located by carefully scrutinizing cine-MRI images for pulsating turbulent flow voids, facilitating a more focused and minimally invasive treatment strategy.¹³

Neo et al¹² used cine-MRI to evaluate and plan the surgical resection of a giant spinal extradural arachnoid cyst. MRI helped determine the initial diagnosis, and a pulsating turbulent flow void was observed by cine-MRI in the area later confirmed surgically to contain the communication between the cyst and the spinal subarachnoid space.

Cine-MRI is not necessary as part of the initial diagnostic evaluation for spinal arachnoid cysts. It is of particular value only to the surgeon, who can request it if needed.

HISTOPATHOLOGY

With hematoxylin and eosin staining, the walls of spinal arachnoid cysts are typically seen as fibrous and lined by meningothelial cells.

TREATMENT

Observe asymptomatic cysts

For incidentally discovered spinal arachnoid cysts that cause no symptoms—ie, most of them—surgery is not recommended. No correlation exists between the size of a cyst and the need for treatment. Yearly imaging should be done to detect any new abnormality and determine whether the cyst is truly benign.

If symptoms arise, reevaluation of the cyst with MRI should be immediately undertaken.

Remove symptomatic cyst if possible

For a patient with symptoms, treatment offers an excellent chance of neurologic recovery.

Aspiration of the cyst is not routinely advised. Although aspiration may intuitively seem like the best initial approach to management, it only temporarily improves symptoms. However, percutaneous aspiration under fluoroscopic guidance may be appropriate for determining whether a cyst is causing a patient’s symptoms and thereby predicting whether surgery can help. Surgery should be undertaken only after careful consideration, as postoperative complications, though uncommon, may be very troublesome for both the patient and the surgeon.

Complete resection is ideal treatment. The standard treatment of an isolated spinal arachnoid cyst is complete surgical removal of the cyst.¹ Surgery typically results in excellent outcomes in terms of resolution of symptoms, and is effective across a large range of cyst sizes.

Drain cysts that cannot be resected. Unfortunately, not all isolated spinal arachnoid cysts can be fully resected, owing to their location or to intraoperative findings such as extensive adhesion of a cyst to the spinal cord. In such cases, fenestration of the cyst wall, percutaneous drainage, or shunting the cyst into the peritoneal cavity may relieve symptoms.^1–3,6

Minimally invasive surgical techniques have also met with some success. Neo et al¹² reported that they successfully treated a giant spinal extradural arachnoid cyst by selectively closing the dural defect with clips. Cine-MRI was used to pinpoint the communication, allowing for a focused, limited surgical approach requiring only fenestration. The dural surface of the cyst was examined with an operating microscope.

Endoscopic approaches have also been used to treat sacral extradural arachnoid cysts.⁷

SOME CASES ARE MORE COMPLEX

Managing spinal arachnoid cysts becomes more complex as cysts become more intricate in morphology and if multiple cysts exist across different vertebral levels. Surgical planning and intraoperative monitoring are also complicated if a spinal arachnoid cyst coexists with another central nervous system problem.

Cases have been reported of patients with coexisting spinal arachnoid cysts and lumbar disk herniation; in many, the latter problem was considered to be the cause of symptoms.⁷

Holly and Batzdorf³ described patients with both intradural arachnoid cysts and syringomyelia. Cysts were resected with the aid of an operating microscope, and intraoperative ultrasonography confirmed that normal pulsation of the subarachnoid cerebrospinal fluid had returned after resection. The syrinx cavities were not surgically manipulated, yet MRI taken 3 months after surgery revealed that they had significantly diminished in each case.

The best predictor of recovery in patients who undergo surgery for spinal arachnoid cysts is if the clinical presentation correlates with the defect.^1,7 Usually the postsurgical prognosis is good, with significant to full neurologic recovery in patients with all cyst types and clinical presentations.

Many patients with spinal arachnoid cysts complain of symptoms suggesting spinal cord compression, and are often initially evaluated by their primary physicians. However, these cysts are often discovered incidentally.

This article discusses how to manage spinal arachnoid cysts, whether found incidentally or during an evaluation for symptoms of spinal cord compression.

PRESENTATIONS CAN VARY WIDELY

A patient with a clinically relevant spinal arachnoid cyst is most likely to be a boy in his teens, but these cysts can occur in either sex and have been reported in patients as young as a few months and as old as nearly 80 years.^1–6

In their typical presentation, spinal arachnoid cysts cause progressive signs and symptoms suggesting spinal cord compression. But because a cyst can occur at any spinal level and in a patient of any age, no one clinical presentation is pathognomonic, and the clinical sequelae can differ drastically from patient to patient. Nevertheless, we can make certain generalizations: a spinal arachnoid cyst that compresses the spinal cord typically causes waxing and waning pain and progressive spastic or flaccid paraparesis, which often are exacerbated by Valsalva maneuvers.^1,6 Spinal arachnoid cysts can also present with symptoms suggestive of an isolated radiculopathy.

Less typical presentations include noncardiac chest pain, isolated gait difficulty, and isolated urinary urgency.^2–4

Missed diagnosis is common

Because the symptoms are so variable and nonspecific, the diagnosis of spinal arachnoid cysts is often missed. For example, a sacral extradural arachnoid cyst can cause pain in the low back and perineal region, which is often relieved by lying flat and aggravated by Valsalva maneuvers.⁷

Complicating the picture, spinal arachnoid cysts can also coexist with other disorders of the central nervous system. Cases have been reported of sacral extradural arachnoid cysts coexisting with lumbar disk prolapse⁷ and of spinal arachnoid cysts located near a syrinx (a tube-shaped cavity in the spinal cord).^3,8 A patient can have more than one spinal arachnoid cyst, or both a spinal arachnoid cyst and a concurrent intracranial arachnoid cyst or a tumor.⁹

EXTRADURAL VS INTRADURAL CYSTS

Like other types of spinal meningeal cysts, spinal arachnoid cysts can be broadly characterized as either extradural or intradural.¹⁰

Extradural cysts are extradural outpouchings of arachnoid that are contiguous with the spinal subarachnoid space via a small dural defect. They typically occur in the thoracic spine dorsal to the spinal cord, although they may be found elsewhere.

Intradural cysts are outpouchings of arachnoid that, regardless of size, lie entirely within the dural space. Intradural arachnoid cysts are more common than extradural cysts.

Either type of cyst may or may not communicate with the subarachnoid space.^1–3

Other cystic lesions of the spine exist. One of the most common is the Tarlov cyst, which may look similar to a spinal arachnoid cyst, as both types of cysts are collections of cerebrospinal fluid. But, unlike typical spinal arachnoid cysts, Tarlov cysts occur only in the sacral spine and appear solely within the sacral root on radiographic imaging.

HOW DO CYSTS FORM?

How spinal arachnoid cysts start to form is open to conjecture, and several theories exist.^1,2,7 They are often attributed to congenital defects. Another possibility is that arachnoid adhesions develop secondary to inflammation, which may arise from infection (meningitis), hemorrhage, or an iatrogenic cause such as injected contrast media or anesthetics or from the intraoperative contaminants of fibrin glue.¹¹ Some cysts are due to trauma from lumbar puncture, anesthetic procedures, or intradural surgery. Other cysts are idiopathic.

WHY DO CYSTS ENLARGE?

Several mechanisms have been proposed to explain why spinal arachnoid cysts enlarge.² The cells in the cyst wall probably do not secrete fluid: many spinal arachnoid cyst walls are composed primarily of simple connective tissue, and many completely lack an inner arachnoid lining—the cells that normally secrete spinal fluid—or have only a sparse lining.⁶ A unidirectional “valve” might let fluid in but not out. Another mechanism is pathologic distribution of arachnoid trabeculae, leading to fluid shifts within the cyst, thereby causing an increase in size.

DIAGNOSIS IS OFTEN INCIDENTAL

Spinal arachnoid cysts are rare, so an algorithm to diagnose them solely on the basis of common presenting symptoms would be impractical.

Whenever an arachnoid cyst is discovered, one must determine whether the cyst—or another problem—is actually causing the symptoms. If treatment is to succeed, the clinical presentation must correspond to the radiographic findings. For example, removing a cervical arachnoid cyst is unlikely to relieve low back pain.

Although most arachnoid cysts are found by MRI, it is inappropriate to initially order MRI to evaluate a cyst’s common presenting symptoms (eg, back pain, radiculopathy).

Plain radiography should be done first. Although arachnoid cysts are composed of fluid and soft tissue, which are not easily detectable on plain films, subtle and indirect signs of a chronic, large cyst may be visible.⁵

MRI is the next step if plain radiographs do not reveal bony abnormalities that could explain a patient’s symptoms.

Further studies help characterize the lesion

Diffusion-weighted MRI can help differentiate an epidermoid cyst from an arachnoid cyst. It may also help differentiate a cyst from an abscess or tumor: abscesses have areas of restricted diffusion, and tumors tend to lack cerebrospinal fluid signal in their central core. Diffusion-weighted MRI can also help evaluate spinal cord atrophy and inflammatory changes.^1,6,12 If an arachnoid cyst accompanies a nerve root as it enters the neural foramen, this would also appear on MRI.

Myelography or computed tomographic (CT) myelography were used to further characterize the form and structure of spinal arachnoid cysts discovered on MRI in most reported cases, and most authors advocate these studies.^1,3,8,12 Specifically, CT myelography has been used to look for a communication between the intraspinal subarachnoid space and the spinal arachnoid cyst, and it is sensitive in determining whether a communication exists, although it does not pinpoint the location of the communication very well.¹² CT myelography is also invaluable for imaging the spine of patients who have contraindications to MRI.

Kinematic MRI (cine-MRI) is now widely available and can help evaluate for the presence of communications between the cyst and the subarachnoid space. Dural defects may be located by carefully scrutinizing cine-MRI images for pulsating turbulent flow voids, facilitating a more focused and minimally invasive treatment strategy.¹³

Neo et al¹² used cine-MRI to evaluate and plan the surgical resection of a giant spinal extradural arachnoid cyst. MRI helped determine the initial diagnosis, and a pulsating turbulent flow void was observed by cine-MRI in the area later confirmed surgically to contain the communication between the cyst and the spinal subarachnoid space.

Cine-MRI is not necessary as part of the initial diagnostic evaluation for spinal arachnoid cysts. It is of particular value only to the surgeon, who can request it if needed.

HISTOPATHOLOGY

With hematoxylin and eosin staining, the walls of spinal arachnoid cysts are typically seen as fibrous and lined by meningothelial cells.

TREATMENT

Observe asymptomatic cysts

For incidentally discovered spinal arachnoid cysts that cause no symptoms—ie, most of them—surgery is not recommended. No correlation exists between the size of a cyst and the need for treatment. Yearly imaging should be done to detect any new abnormality and determine whether the cyst is truly benign.

If symptoms arise, reevaluation of the cyst with MRI should be immediately undertaken.

Remove symptomatic cyst if possible

For a patient with symptoms, treatment offers an excellent chance of neurologic recovery.

Aspiration of the cyst is not routinely advised. Although aspiration may intuitively seem like the best initial approach to management, it only temporarily improves symptoms. However, percutaneous aspiration under fluoroscopic guidance may be appropriate for determining whether a cyst is causing a patient’s symptoms and thereby predicting whether surgery can help. Surgery should be undertaken only after careful consideration, as postoperative complications, though uncommon, may be very troublesome for both the patient and the surgeon.

Complete resection is ideal treatment. The standard treatment of an isolated spinal arachnoid cyst is complete surgical removal of the cyst.¹ Surgery typically results in excellent outcomes in terms of resolution of symptoms, and is effective across a large range of cyst sizes.

Drain cysts that cannot be resected. Unfortunately, not all isolated spinal arachnoid cysts can be fully resected, owing to their location or to intraoperative findings such as extensive adhesion of a cyst to the spinal cord. In such cases, fenestration of the cyst wall, percutaneous drainage, or shunting the cyst into the peritoneal cavity may relieve symptoms.^1–3,6

Minimally invasive surgical techniques have also met with some success. Neo et al¹² reported that they successfully treated a giant spinal extradural arachnoid cyst by selectively closing the dural defect with clips. Cine-MRI was used to pinpoint the communication, allowing for a focused, limited surgical approach requiring only fenestration. The dural surface of the cyst was examined with an operating microscope.

Endoscopic approaches have also been used to treat sacral extradural arachnoid cysts.⁷

SOME CASES ARE MORE COMPLEX

Managing spinal arachnoid cysts becomes more complex as cysts become more intricate in morphology and if multiple cysts exist across different vertebral levels. Surgical planning and intraoperative monitoring are also complicated if a spinal arachnoid cyst coexists with another central nervous system problem.

Cases have been reported of patients with coexisting spinal arachnoid cysts and lumbar disk herniation; in many, the latter problem was considered to be the cause of symptoms.⁷

Holly and Batzdorf³ described patients with both intradural arachnoid cysts and syringomyelia. Cysts were resected with the aid of an operating microscope, and intraoperative ultrasonography confirmed that normal pulsation of the subarachnoid cerebrospinal fluid had returned after resection. The syrinx cavities were not surgically manipulated, yet MRI taken 3 months after surgery revealed that they had significantly diminished in each case.

The best predictor of recovery in patients who undergo surgery for spinal arachnoid cysts is if the clinical presentation correlates with the defect.^1,7 Usually the postsurgical prognosis is good, with significant to full neurologic recovery in patients with all cyst types and clinical presentations.

Echocardiographically measured left atrial size was significantly related to ischemic stroke and all-cause mortality in a follow-up analysis of 1,886 blacks in the Atherosclerosis Risk in Communities study.

At a median of 9 years follow-up, there were 103 strokes (6.47/1,000 person-years) and 206 deaths (13.3/1,000 person-years) in participants in the Jackson, Miss., cohort of the study. Their mean age was 59 years; 65% were women.

Left atrial size was significantly related to hypertension, diabetes, and body mass index, Dr. Harsha S. Nagarajarao reported at the American Federation for Medical Research Southern Regional meeting in New Orleans.

In an effort to adjust left atrial (LA) size to body size, LA size was indexed to height and was then divided into quintiles, with 377 patients in the top quintile of LA size (2.57–3.55 cm/m) and 1,509 patients in the bottom four quintiles (1.29–2.56 cm/m). Significantly more patients in the top quintile of LA size were hypertensive (74.3% vs. 57%), diabetic (29% vs. 21.3%), and had a higher mean BMI, compared with those with lower LA size (34.6 vs. 29.4 kg/m

In a multivariate analysis, LA size on echocardiogram was significantly associated with ischemic stroke (hazard ratio 1.58) and all-cause mortality (HR 1.47), even after adjustment for age, sex, cigarette smoking, diabetes, hypertension, BMI, ratio of total cholesterol to HDL cholesterol, and triglyceride levels.

Left atrial size remained significantly related to all-cause mortality (HR 1.40) after further adjustment for left ventricular hypertrophy, Dr. Nagarajarao of the University of Mississippi Medical Center, in Jackson, and colleagues reported.

Non-Hispanic whites also have an increased incidence of stroke with increased LA size, but LA size is more important in blacks because of that population's increased stroke risk, Dr. Nagarajarao said in an interview. Blacks have a twofold higher incidence of stroke when compared with non-Hispanic whites, he added.

“Echocardiography may be a potentially useful noninvasive tool in identifying additional risk factors for stroke, and identifying participants with larger LA size may allow us to take preventive measures in identifying risk factors and treating them,” he said.

Last year, investigators at the University of Mississippi Medical Center also reported that echocardiographically derived left ventricular mass index (LVMI) was an independent predictor of incident ischemic stroke among 1,792 blacks in the Jackson cohort, after adjustment for similar cardiovascular risk factors (Stroke 2007;38:2686–91). In addition, the relation between LVMI and stroke remained significant after adding LA size and mitral annular calcification to the multivariable analysis.

Clinicians at the center determine LA size routinely on echocardiography in all patients at risk of stroke, Dr. Nagarajarao said. When asked which measurement is preferred, he said both LVMI and LA size have the potential to be independent predictors of risk factors, adding that it is important to recognize that each is independent of the other.

Previous studies have shown that the BP medication hydrochlorothiazide has reduced LA size when used along with controlling hypertension, although further study is needed to determine whether this has any effect on reducing stroke incidence, he said.

Echocardiographically measured left atrial size was significantly related to ischemic stroke and all-cause mortality in a follow-up analysis of 1,886 blacks in the Atherosclerosis Risk in Communities study.

At a median of 9 years follow-up, there were 103 strokes (6.47/1,000 person-years) and 206 deaths (13.3/1,000 person-years) in participants in the Jackson, Miss., cohort of the study. Their mean age was 59 years; 65% were women.

Left atrial size was significantly related to hypertension, diabetes, and body mass index, Dr. Harsha S. Nagarajarao reported at the American Federation for Medical Research Southern Regional meeting in New Orleans.

In an effort to adjust left atrial (LA) size to body size, LA size was indexed to height and was then divided into quintiles, with 377 patients in the top quintile of LA size (2.57–3.55 cm/m) and 1,509 patients in the bottom four quintiles (1.29–2.56 cm/m). Significantly more patients in the top quintile of LA size were hypertensive (74.3% vs. 57%), diabetic (29% vs. 21.3%), and had a higher mean BMI, compared with those with lower LA size (34.6 vs. 29.4 kg/m

In a multivariate analysis, LA size on echocardiogram was significantly associated with ischemic stroke (hazard ratio 1.58) and all-cause mortality (HR 1.47), even after adjustment for age, sex, cigarette smoking, diabetes, hypertension, BMI, ratio of total cholesterol to HDL cholesterol, and triglyceride levels.

Left atrial size remained significantly related to all-cause mortality (HR 1.40) after further adjustment for left ventricular hypertrophy, Dr. Nagarajarao of the University of Mississippi Medical Center, in Jackson, and colleagues reported.

Non-Hispanic whites also have an increased incidence of stroke with increased LA size, but LA size is more important in blacks because of that population's increased stroke risk, Dr. Nagarajarao said in an interview. Blacks have a twofold higher incidence of stroke when compared with non-Hispanic whites, he added.

“Echocardiography may be a potentially useful noninvasive tool in identifying additional risk factors for stroke, and identifying participants with larger LA size may allow us to take preventive measures in identifying risk factors and treating them,” he said.

Last year, investigators at the University of Mississippi Medical Center also reported that echocardiographically derived left ventricular mass index (LVMI) was an independent predictor of incident ischemic stroke among 1,792 blacks in the Jackson cohort, after adjustment for similar cardiovascular risk factors (Stroke 2007;38:2686–91). In addition, the relation between LVMI and stroke remained significant after adding LA size and mitral annular calcification to the multivariable analysis.

Clinicians at the center determine LA size routinely on echocardiography in all patients at risk of stroke, Dr. Nagarajarao said. When asked which measurement is preferred, he said both LVMI and LA size have the potential to be independent predictors of risk factors, adding that it is important to recognize that each is independent of the other.

Previous studies have shown that the BP medication hydrochlorothiazide has reduced LA size when used along with controlling hypertension, although further study is needed to determine whether this has any effect on reducing stroke incidence, he said.

Echocardiographically measured left atrial size was significantly related to ischemic stroke and all-cause mortality in a follow-up analysis of 1,886 blacks in the Atherosclerosis Risk in Communities study.

At a median of 9 years follow-up, there were 103 strokes (6.47/1,000 person-years) and 206 deaths (13.3/1,000 person-years) in participants in the Jackson, Miss., cohort of the study. Their mean age was 59 years; 65% were women.

Left atrial size was significantly related to hypertension, diabetes, and body mass index, Dr. Harsha S. Nagarajarao reported at the American Federation for Medical Research Southern Regional meeting in New Orleans.

In an effort to adjust left atrial (LA) size to body size, LA size was indexed to height and was then divided into quintiles, with 377 patients in the top quintile of LA size (2.57–3.55 cm/m) and 1,509 patients in the bottom four quintiles (1.29–2.56 cm/m). Significantly more patients in the top quintile of LA size were hypertensive (74.3% vs. 57%), diabetic (29% vs. 21.3%), and had a higher mean BMI, compared with those with lower LA size (34.6 vs. 29.4 kg/m

In a multivariate analysis, LA size on echocardiogram was significantly associated with ischemic stroke (hazard ratio 1.58) and all-cause mortality (HR 1.47), even after adjustment for age, sex, cigarette smoking, diabetes, hypertension, BMI, ratio of total cholesterol to HDL cholesterol, and triglyceride levels.

Left atrial size remained significantly related to all-cause mortality (HR 1.40) after further adjustment for left ventricular hypertrophy, Dr. Nagarajarao of the University of Mississippi Medical Center, in Jackson, and colleagues reported.

Non-Hispanic whites also have an increased incidence of stroke with increased LA size, but LA size is more important in blacks because of that population's increased stroke risk, Dr. Nagarajarao said in an interview. Blacks have a twofold higher incidence of stroke when compared with non-Hispanic whites, he added.

“Echocardiography may be a potentially useful noninvasive tool in identifying additional risk factors for stroke, and identifying participants with larger LA size may allow us to take preventive measures in identifying risk factors and treating them,” he said.

Last year, investigators at the University of Mississippi Medical Center also reported that echocardiographically derived left ventricular mass index (LVMI) was an independent predictor of incident ischemic stroke among 1,792 blacks in the Jackson cohort, after adjustment for similar cardiovascular risk factors (Stroke 2007;38:2686–91). In addition, the relation between LVMI and stroke remained significant after adding LA size and mitral annular calcification to the multivariable analysis.

Clinicians at the center determine LA size routinely on echocardiography in all patients at risk of stroke, Dr. Nagarajarao said. When asked which measurement is preferred, he said both LVMI and LA size have the potential to be independent predictors of risk factors, adding that it is important to recognize that each is independent of the other.

Previous studies have shown that the BP medication hydrochlorothiazide has reduced LA size when used along with controlling hypertension, although further study is needed to determine whether this has any effect on reducing stroke incidence, he said.

SNOWMASS, COLO. — The most intriguing potential application for coronary artery calcium imaging is as a tool to track atherosclerosis progression over time in response to treatment, Dr. Matthew J. Budoff said at a conference sponsored by the Society for Cardiovascular Angiography and Interventions.

“I'm not suggesting that this is a current application, but the data now emerging are pretty interesting,” according to Dr. Budoff, director of cardiac CT at Harbor-UCLA Medical Center, Torrance, Calif.

He cited an observational study in which investigators tracked the change in coronary artery calcium (CAC) on serial electron-beam CT scans in 495 statin-treated asymptomatic patients. Forty-one subjects had an acute MI during up to 7 years of follow-up. The relative risk of an MI was increased 17-fold in those with at least a 15% per year rise in CAC score (Arterioscler. Thromb. Vasc. Biol.2004;24:1272–7).

“This might be a way, in the future, of monitoring therapy. You're on a statin, your LDL is pretty good, but your CAC is increasing—maybe we should do something more,” Dr. Budoff said at the conference cosponsored by the ACC.

He also described several current uses for CAC imaging:

▸ Screening asymptomatic patients with an intermediate Framingham risk score. Forty percent of asymptomatic adults fall into the Framingham intermediate-risk category, meaning they have an estimated 10%–20% risk of a coronary event within the next 10 years. Most acute MIs occur in this mid-risk group. Dr. Budoff was coauthor of a 2007 ACC/AHA Clinical Expert Consensus Statement that endorsed CAC measurement as a means of further stratifying Framingham intermediate-risk patients in order to identify a higher-risk subgroup in whom aggressive primary preventive measures are warranted (J. Am. Coll. Cardiol. 2007;49:378–402).

The Multi-Ethnic Study of Atherosclerosis (MESA), a National Institutes of Health-sponsored prospective study of 6,814 patients followed for 3.5 years now in press, was merely the most recent of several large studies showing that a CAC score of 100 or more was associated with a 10-fold increased risk of incident coronary heart disease.

And a prospective study sponsored by the NIH of more than 10,700 asymptomatic persons free of known coronary heart disease when they underwent CAC measurement showed that a baseline CAC of 97–409 was linked with an adjusted 9.7-fold greater risk of nonfatal MI or CHD death in the next 3.5 years, compared with subjects with a CAC of 0 (Am. J. Epidemiol. 2005;162:421–9).

“A CAC greater than 100 is more robust as a predictor of future events than Framingham risk factors … and more robust than C-reactive protein or carotid intimal-medial thickness,” observed Dr. Budoff, who is on the speakers bureau for General Electric.

▸ Identification of very-low-risk patients needing no further evaluation for coronary artery disease. Four studies totalling nearly 6,000 patients indicate a CAC of 0 has a 95%–99% negative predictive value for obstructive coronary disease. A fifth study, by Dr. Budoff and coinvestigators, concluded that a CAC score of 0 on an initial scan has at least a 5-year warranty before a repeat scan is appropriate because the likelihood of CAC progression during that first half-decade is so low (Int. J. Cardiol. 2007;117:227–31).

▸ A tool to improve compliance. In a study by Dr. Budoff's group, showing patients their CAC image was tied with 91% adherence to statin therapy over 3 years among those who scored in the top CAC quartile (Atherosclerosis 2006;185:394–9).

SNOWMASS, COLO. — The most intriguing potential application for coronary artery calcium imaging is as a tool to track atherosclerosis progression over time in response to treatment, Dr. Matthew J. Budoff said at a conference sponsored by the Society for Cardiovascular Angiography and Interventions.

“I'm not suggesting that this is a current application, but the data now emerging are pretty interesting,” according to Dr. Budoff, director of cardiac CT at Harbor-UCLA Medical Center, Torrance, Calif.

He cited an observational study in which investigators tracked the change in coronary artery calcium (CAC) on serial electron-beam CT scans in 495 statin-treated asymptomatic patients. Forty-one subjects had an acute MI during up to 7 years of follow-up. The relative risk of an MI was increased 17-fold in those with at least a 15% per year rise in CAC score (Arterioscler. Thromb. Vasc. Biol.2004;24:1272–7).

“This might be a way, in the future, of monitoring therapy. You're on a statin, your LDL is pretty good, but your CAC is increasing—maybe we should do something more,” Dr. Budoff said at the conference cosponsored by the ACC.

He also described several current uses for CAC imaging:

▸ Screening asymptomatic patients with an intermediate Framingham risk score. Forty percent of asymptomatic adults fall into the Framingham intermediate-risk category, meaning they have an estimated 10%–20% risk of a coronary event within the next 10 years. Most acute MIs occur in this mid-risk group. Dr. Budoff was coauthor of a 2007 ACC/AHA Clinical Expert Consensus Statement that endorsed CAC measurement as a means of further stratifying Framingham intermediate-risk patients in order to identify a higher-risk subgroup in whom aggressive primary preventive measures are warranted (J. Am. Coll. Cardiol. 2007;49:378–402).

The Multi-Ethnic Study of Atherosclerosis (MESA), a National Institutes of Health-sponsored prospective study of 6,814 patients followed for 3.5 years now in press, was merely the most recent of several large studies showing that a CAC score of 100 or more was associated with a 10-fold increased risk of incident coronary heart disease.

And a prospective study sponsored by the NIH of more than 10,700 asymptomatic persons free of known coronary heart disease when they underwent CAC measurement showed that a baseline CAC of 97–409 was linked with an adjusted 9.7-fold greater risk of nonfatal MI or CHD death in the next 3.5 years, compared with subjects with a CAC of 0 (Am. J. Epidemiol. 2005;162:421–9).

“A CAC greater than 100 is more robust as a predictor of future events than Framingham risk factors … and more robust than C-reactive protein or carotid intimal-medial thickness,” observed Dr. Budoff, who is on the speakers bureau for General Electric.

▸ Identification of very-low-risk patients needing no further evaluation for coronary artery disease. Four studies totalling nearly 6,000 patients indicate a CAC of 0 has a 95%–99% negative predictive value for obstructive coronary disease. A fifth study, by Dr. Budoff and coinvestigators, concluded that a CAC score of 0 on an initial scan has at least a 5-year warranty before a repeat scan is appropriate because the likelihood of CAC progression during that first half-decade is so low (Int. J. Cardiol. 2007;117:227–31).

▸ A tool to improve compliance. In a study by Dr. Budoff's group, showing patients their CAC image was tied with 91% adherence to statin therapy over 3 years among those who scored in the top CAC quartile (Atherosclerosis 2006;185:394–9).

SNOWMASS, COLO. — The most intriguing potential application for coronary artery calcium imaging is as a tool to track atherosclerosis progression over time in response to treatment, Dr. Matthew J. Budoff said at a conference sponsored by the Society for Cardiovascular Angiography and Interventions.

“I'm not suggesting that this is a current application, but the data now emerging are pretty interesting,” according to Dr. Budoff, director of cardiac CT at Harbor-UCLA Medical Center, Torrance, Calif.

He cited an observational study in which investigators tracked the change in coronary artery calcium (CAC) on serial electron-beam CT scans in 495 statin-treated asymptomatic patients. Forty-one subjects had an acute MI during up to 7 years of follow-up. The relative risk of an MI was increased 17-fold in those with at least a 15% per year rise in CAC score (Arterioscler. Thromb. Vasc. Biol.2004;24:1272–7).

“This might be a way, in the future, of monitoring therapy. You're on a statin, your LDL is pretty good, but your CAC is increasing—maybe we should do something more,” Dr. Budoff said at the conference cosponsored by the ACC.

He also described several current uses for CAC imaging:

▸ Screening asymptomatic patients with an intermediate Framingham risk score. Forty percent of asymptomatic adults fall into the Framingham intermediate-risk category, meaning they have an estimated 10%–20% risk of a coronary event within the next 10 years. Most acute MIs occur in this mid-risk group. Dr. Budoff was coauthor of a 2007 ACC/AHA Clinical Expert Consensus Statement that endorsed CAC measurement as a means of further stratifying Framingham intermediate-risk patients in order to identify a higher-risk subgroup in whom aggressive primary preventive measures are warranted (J. Am. Coll. Cardiol. 2007;49:378–402).

The Multi-Ethnic Study of Atherosclerosis (MESA), a National Institutes of Health-sponsored prospective study of 6,814 patients followed for 3.5 years now in press, was merely the most recent of several large studies showing that a CAC score of 100 or more was associated with a 10-fold increased risk of incident coronary heart disease.

And a prospective study sponsored by the NIH of more than 10,700 asymptomatic persons free of known coronary heart disease when they underwent CAC measurement showed that a baseline CAC of 97–409 was linked with an adjusted 9.7-fold greater risk of nonfatal MI or CHD death in the next 3.5 years, compared with subjects with a CAC of 0 (Am. J. Epidemiol. 2005;162:421–9).

“A CAC greater than 100 is more robust as a predictor of future events than Framingham risk factors … and more robust than C-reactive protein or carotid intimal-medial thickness,” observed Dr. Budoff, who is on the speakers bureau for General Electric.

▸ Identification of very-low-risk patients needing no further evaluation for coronary artery disease. Four studies totalling nearly 6,000 patients indicate a CAC of 0 has a 95%–99% negative predictive value for obstructive coronary disease. A fifth study, by Dr. Budoff and coinvestigators, concluded that a CAC score of 0 on an initial scan has at least a 5-year warranty before a repeat scan is appropriate because the likelihood of CAC progression during that first half-decade is so low (Int. J. Cardiol. 2007;117:227–31).

▸ A tool to improve compliance. In a study by Dr. Budoff's group, showing patients their CAC image was tied with 91% adherence to statin therapy over 3 years among those who scored in the top CAC quartile (Atherosclerosis 2006;185:394–9).

The American College of Cardiology Foundation and key specialty societies have released new appropriateness criteria for the use of stress echocardiography in an ongoing effort to help physicians keep abreast of rapidly changing imaging technology.

The indications in the “2008 Appropriateness Criteria for Stress Echocardiography” are intended to identify common scenarios encompassing most of current practice and are part of a systematic evaluation of the utility of diagnostic imaging tests in common clinical situations (Circulation 2008 March 3 [doi:10.1161/circulationaha.107.189097]).

In all, 51 indications were considered. Of these, stress echocardiography was found to be appropriate for 22, uncertain for 10, and inappropriate for 19. The use of stress echocardiography for the detection of coronary artery disease (CAD) in symptomatic patients was generally deemed to be appropriate. Routine repeat testing, general screening, and postrevascularization risk assessment were generally viewed less favorably.

All indications were assumed to apply only to adult patients (18 years or older). It was also assumed that the test is performed and interpreted by qualified individuals in facilities that are proficient in the imaging technique.

Panelists were also instructed to make several assumptions specifically for stress echocardiography.

▸ All standard echocardiographic techniques for image acquisition are available for each indication; and stress echocardiography has a sensitivity and specificity similar to those in the published literature.

▸ The mode of stress testing is assumed to be exercise, unless the patient is unable to do so. For those patients who cannot exercise, it is assumed that dobutamine is used.

▸ Preoperative evaluation includes procedures such as organ transplantation. Panelists also were asked not to consider other imaging modalities or other appropriateness criteria while rating indications.

An imaging study was considered appropriate if the expected incremental information, combined with clinical judgment, “exceeded the expected negative consequences by a sufficiently wide margin for a specific indication that the procedure is generally considered acceptable care and a reasonable approach for the indication,” the panel wrote. “Inappropriate use may be costly and may prompt potentially harmful and costly downstream testing and treatment such as unwarranted coronary revascularization or unnecessary repeat follow-up.”

Appropriateness was indicated by a score from 7 to 9. The test is generally acceptable and is a reasonable approach for the specific indication. Inappropriateness was indicated by a score of 1–3. The test is generally not acceptable and is not a reasonable approach for the indication. Tests scoring from 4 to 6 were considered uncertain for specific indications. The test may be generally acceptable and may be a reasonable approach for the indication; more research and/or patient information is needed to classify the indication definitively.

“Although the appropriateness ratings reflect a general expert consensus of when stress echocardiography may or may not be useful for specific patient populations, physicians and other stakeholders should understand the role of clinical judgment in determining whether to order a test for an individual patient.” For example, an inappropriate rating does not rule out the use of stress echocardiography when there are patient- and condition-specific data to support that decision.

The American College of Cardiology Foundation and key specialty societies have released new appropriateness criteria for the use of stress echocardiography in an ongoing effort to help physicians keep abreast of rapidly changing imaging technology.

The indications in the “2008 Appropriateness Criteria for Stress Echocardiography” are intended to identify common scenarios encompassing most of current practice and are part of a systematic evaluation of the utility of diagnostic imaging tests in common clinical situations (Circulation 2008 March 3 [doi:10.1161/circulationaha.107.189097]).

In all, 51 indications were considered. Of these, stress echocardiography was found to be appropriate for 22, uncertain for 10, and inappropriate for 19. The use of stress echocardiography for the detection of coronary artery disease (CAD) in symptomatic patients was generally deemed to be appropriate. Routine repeat testing, general screening, and postrevascularization risk assessment were generally viewed less favorably.

All indications were assumed to apply only to adult patients (18 years or older). It was also assumed that the test is performed and interpreted by qualified individuals in facilities that are proficient in the imaging technique.

Panelists were also instructed to make several assumptions specifically for stress echocardiography.

▸ All standard echocardiographic techniques for image acquisition are available for each indication; and stress echocardiography has a sensitivity and specificity similar to those in the published literature.

▸ The mode of stress testing is assumed to be exercise, unless the patient is unable to do so. For those patients who cannot exercise, it is assumed that dobutamine is used.

▸ Preoperative evaluation includes procedures such as organ transplantation. Panelists also were asked not to consider other imaging modalities or other appropriateness criteria while rating indications.

An imaging study was considered appropriate if the expected incremental information, combined with clinical judgment, “exceeded the expected negative consequences by a sufficiently wide margin for a specific indication that the procedure is generally considered acceptable care and a reasonable approach for the indication,” the panel wrote. “Inappropriate use may be costly and may prompt potentially harmful and costly downstream testing and treatment such as unwarranted coronary revascularization or unnecessary repeat follow-up.”

Appropriateness was indicated by a score from 7 to 9. The test is generally acceptable and is a reasonable approach for the specific indication. Inappropriateness was indicated by a score of 1–3. The test is generally not acceptable and is not a reasonable approach for the indication. Tests scoring from 4 to 6 were considered uncertain for specific indications. The test may be generally acceptable and may be a reasonable approach for the indication; more research and/or patient information is needed to classify the indication definitively.

“Although the appropriateness ratings reflect a general expert consensus of when stress echocardiography may or may not be useful for specific patient populations, physicians and other stakeholders should understand the role of clinical judgment in determining whether to order a test for an individual patient.” For example, an inappropriate rating does not rule out the use of stress echocardiography when there are patient- and condition-specific data to support that decision.

The American College of Cardiology Foundation and key specialty societies have released new appropriateness criteria for the use of stress echocardiography in an ongoing effort to help physicians keep abreast of rapidly changing imaging technology.

The indications in the “2008 Appropriateness Criteria for Stress Echocardiography” are intended to identify common scenarios encompassing most of current practice and are part of a systematic evaluation of the utility of diagnostic imaging tests in common clinical situations (Circulation 2008 March 3 [doi:10.1161/circulationaha.107.189097]).

In all, 51 indications were considered. Of these, stress echocardiography was found to be appropriate for 22, uncertain for 10, and inappropriate for 19. The use of stress echocardiography for the detection of coronary artery disease (CAD) in symptomatic patients was generally deemed to be appropriate. Routine repeat testing, general screening, and postrevascularization risk assessment were generally viewed less favorably.

All indications were assumed to apply only to adult patients (18 years or older). It was also assumed that the test is performed and interpreted by qualified individuals in facilities that are proficient in the imaging technique.

Panelists were also instructed to make several assumptions specifically for stress echocardiography.

▸ All standard echocardiographic techniques for image acquisition are available for each indication; and stress echocardiography has a sensitivity and specificity similar to those in the published literature.

▸ The mode of stress testing is assumed to be exercise, unless the patient is unable to do so. For those patients who cannot exercise, it is assumed that dobutamine is used.

▸ Preoperative evaluation includes procedures such as organ transplantation. Panelists also were asked not to consider other imaging modalities or other appropriateness criteria while rating indications.

An imaging study was considered appropriate if the expected incremental information, combined with clinical judgment, “exceeded the expected negative consequences by a sufficiently wide margin for a specific indication that the procedure is generally considered acceptable care and a reasonable approach for the indication,” the panel wrote. “Inappropriate use may be costly and may prompt potentially harmful and costly downstream testing and treatment such as unwarranted coronary revascularization or unnecessary repeat follow-up.”

Appropriateness was indicated by a score from 7 to 9. The test is generally acceptable and is a reasonable approach for the specific indication. Inappropriateness was indicated by a score of 1–3. The test is generally not acceptable and is not a reasonable approach for the indication. Tests scoring from 4 to 6 were considered uncertain for specific indications. The test may be generally acceptable and may be a reasonable approach for the indication; more research and/or patient information is needed to classify the indication definitively.

“Although the appropriateness ratings reflect a general expert consensus of when stress echocardiography may or may not be useful for specific patient populations, physicians and other stakeholders should understand the role of clinical judgment in determining whether to order a test for an individual patient.” For example, an inappropriate rating does not rule out the use of stress echocardiography when there are patient- and condition-specific data to support that decision.

Sodium phosphate (NaP) agents were introduced to provide a gentler alternative to polyethylene glycol (PEG) bowel preparations, which require patients to drink up to 4 liters of fluid over a few hours.

However, in May 2006 the US Food and Drug Administration (FDA) issued an alert that NaP products for bowel cleansing may, in some patients, pose a risk of acute phosphate nephropathy, a rare form of acute renal failure.

Although NaP preparations are generally safe and well tolerated, they can cause significant fluid shifts and electrolyte abnormalities. As such, they should not be used in patients with baseline electrolyte imbalances, renal or hepatic dysfunction, or a number of other comorbidities.

CURRENT BOWEL-CLEANSING OPTIONS

For many years the standard preparation for bowel cleansing was a 4-liter or a 2-liter PEG electrolyte solution plus a laxative (eg, magnesium citrate, bisacodyl, or senna).^1–3 The most frequent complaint heard from patients was that “the preparation is worse than the colonoscopy,” attributable to the taste and volume of the fluid they had to consume. Thus, compliance was often a significant issue with patients presenting for colonoscopy. In fact, inadequate bowel preparation is one of the most common reasons polyps are missed during colonoscopy.

Aqueous and tablet forms of NaP (sometimes with a laxative) have become a widely used alternative to PEG solutions because they require much less volume and as a result are more palatable, thereby improving compliance.^4,5

NaP agents cleanse the colon by osmotically drawing plasma water into the bowel lumen. The patient must drink significant amounts of water or other oral solutions to prevent dehydration.

NaP-based bowel-cleansing agents are available in two forms: aqueous solution and tablet. Aqueous NaP (such as Fleet Phospho-soda) is a low-volume hyperosmotic solution containing 48 g of monobasic NaP and 18 g of dibasic NaP per 100 mL.⁶ An oral tablet form (such as Visicol and OsmoPrep) was developed to improve patient tolerance.⁷ Each 2-g tablet of Visicol contains 1,500 mg of active ingredients (monobasic and dibasic NaP) and 460 mg of microcrystalline cellulose, an inert polymer. Each OsmoPrep tablet contains 1,500 mg of the same active ingredients as Visicol, but the inert ingredients include PEG and magnesium stearate.

At first, the regimen was 40 tablets such as Visicol to be taken with water and bisacodyl. Subsequent regimens such as OsmoPrep with fewer tablets have been shown to be as effective and better tolerated.⁸ Microcrystalline cellulose in the tablet can produce a residue that may obscure the bowel mucosa. Newer preparations contain lower amounts of this inert ingredient, allowing for improved visualization of the colonic mucosa during colonoscopy.⁹

ADVANTAGES OF SODIUM PHOSPHATE BOWEL CLEANSERS

In a recent review article, Burke and Church¹⁰ noted that NaP cleansing regimens have been shown to be superior to PEG-electrolyte lavage solution with respect to tolerability and acceptance by patients, improved quality of bowel preparation, better mucosal visualization, and more efficient endoscopic examination. In addition, the volume of the preparation may also help decrease the risk of aspiration in some patients.^2,3

DISADVANTAGES OF SODIUM PHOSPHATE AGENTS

Despite their comparable or better efficacy and their better tolerability, NaP agents have certain disadvantages.

Effects on the colonic mucosa

In rare cases NaP agents have been shown to alter the microscopic and macroscopic features of the colonic mucosa, and they can induce aphthoid erosions that may mimic those seen in inflammatory bowel disease and enteropathy or colopathy associated with nonsteroidal anti-inflammatory drugs (NSAIDs).^11–13 Therefore, NaP agents should not be used prior to the initial endoscopic evaluation of patients with suspected inflammatory bowel disease, microscopic colitis, or NSAID-induced colonopathy.

Fluid and electrolyte shifts

Because NaP acts by drawing plasma water into the bowel lumen, significant volume and electrolyte shifts may occur.^14,15 These can cause hypokalemia, hyperphosphatemia, hypocalcemia, hyponatremia or hypernatremia, hypomagnesemia, elevated blood urea nitrogen levels, decreased exercise capacity, increased plasma osmolarity,^15–17 seizures,¹⁸ and acute renal failure with or without nephrocalcinosis.^17,19–21

Thus, patients with significant comorbidities—such as a recent history of myocardial infarction, renal or hepatic insufficiency, or malnutrition—should not use NaP agents.²²

Pivotal study of adverse events

In May 2006, the FDA issued an alert outlining the concerns of using oral NaP in specific patient populations. Of note were documented cases of acute phosphate nephropathy in 21 patients who used aqueous NaP (Fleet Phospho-Soda or Fleet Accu-Prep), and in 1 patient who used NaP tablets (Visicol).²³ Acute renal injury was not limited to patients with preexisting renal insufficiency. It is uncertain whether this means that otherwise healthy people suffered renal injury or had risk factors besides renal insufficiency, since the data cited by the FDA report do not elucidate the possible risk factors for the development of nephropathy in patients with no preexisting renal insufficiency. So far, no cases of acute phosphate nephropathy or acute renal failure have been reported with OsmoPrep, a NaP tablet bowel preparation recently approved by the FDA.²⁴ The long-term safety of OsmoPrep needs further evaluation.

PROCEED WITH CAUTION

Certain situations such as advanced age and cardiac, renal, and hepatic dysfunction call for extreme caution in the use of NaP bowel preparation agents. Therefore, it is recommended that patients with the following conditions should avoid using NaP agents for colon preparation:

• Hepatic or renal insufficiency (there are no data as to the degree of hepatic or renal insufficiency)
• Congestive heart failure
• Over age 65
• Dehydration or hypercalcemia
• Chronic use of drugs that affect renal perfusion, such as NSAIDs, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, or diuretics for hypertension.

Patients who take diuretics should not take them while they are using NaP for bowel preparation because of the risk of electrolyte abnormalities such as hypokalemia. In patients who have no alternative but to proceed with NaP preparation, our recommendation would be that the patient hold off taking diuretics, ACE inhibitors, and angiotensin receptor blockers while using the NaP prep. Given the importance of these medications in controlling diseases such as hypertension, the physician and the patient should jointly determine whether the benefits of using an NaP agent justify holding these drugs. We believe that patients taking these drugs should try using a PEG solution before considering NaP.

TASK FORCE GUIDELINES

Guidelines for using NaP bowel preparation agents, published by a task force of the American Society of Colon and Rectal Surgeons, the American Society for Gastrointestinal Endoscopy, and the Society of American Gastrointestinal and Endoscopic Surgeons,²⁵ include the following caveats:

• Aqueous and tablet NaP colonic preparations are an alternative to PEG solutions, except in pediatric populations, patients over age 65, and those with bowel obstruction or other structural intestinal disorder, gut dysmotility, renal or hepatic insufficiency, congestive heart failure, or seizure disorder.
• Dosing should be 45 mL in divided doses, 10 to 12 hours apart, with at least one dose taken on the morning of the procedure.²⁵
• The significant volume contraction and resulting dehydration seen in some patients using NaP preparations may be lessened by encouraging patients to drink fluids liberally during the days leading up to their procedure, and especially during NaP bowel preparation.²⁶
• NaP tablets should be dosed as 32 to 40 tablets. On the evening before the procedure the patient should take 20 tablets and then 12 to 20 tablets approximately 3 to 5 hours before undergoing endoscopy. The tablets should be taken four at a time every 15 minutes with approximately 8 oz of clear liquid.²⁵

Sodium phosphate (NaP) agents were introduced to provide a gentler alternative to polyethylene glycol (PEG) bowel preparations, which require patients to drink up to 4 liters of fluid over a few hours.

However, in May 2006 the US Food and Drug Administration (FDA) issued an alert that NaP products for bowel cleansing may, in some patients, pose a risk of acute phosphate nephropathy, a rare form of acute renal failure.

Although NaP preparations are generally safe and well tolerated, they can cause significant fluid shifts and electrolyte abnormalities. As such, they should not be used in patients with baseline electrolyte imbalances, renal or hepatic dysfunction, or a number of other comorbidities.

CURRENT BOWEL-CLEANSING OPTIONS

For many years the standard preparation for bowel cleansing was a 4-liter or a 2-liter PEG electrolyte solution plus a laxative (eg, magnesium citrate, bisacodyl, or senna).^1–3 The most frequent complaint heard from patients was that “the preparation is worse than the colonoscopy,” attributable to the taste and volume of the fluid they had to consume. Thus, compliance was often a significant issue with patients presenting for colonoscopy. In fact, inadequate bowel preparation is one of the most common reasons polyps are missed during colonoscopy.

Aqueous and tablet forms of NaP (sometimes with a laxative) have become a widely used alternative to PEG solutions because they require much less volume and as a result are more palatable, thereby improving compliance.^4,5

NaP agents cleanse the colon by osmotically drawing plasma water into the bowel lumen. The patient must drink significant amounts of water or other oral solutions to prevent dehydration.

NaP-based bowel-cleansing agents are available in two forms: aqueous solution and tablet. Aqueous NaP (such as Fleet Phospho-soda) is a low-volume hyperosmotic solution containing 48 g of monobasic NaP and 18 g of dibasic NaP per 100 mL.⁶ An oral tablet form (such as Visicol and OsmoPrep) was developed to improve patient tolerance.⁷ Each 2-g tablet of Visicol contains 1,500 mg of active ingredients (monobasic and dibasic NaP) and 460 mg of microcrystalline cellulose, an inert polymer. Each OsmoPrep tablet contains 1,500 mg of the same active ingredients as Visicol, but the inert ingredients include PEG and magnesium stearate.

At first, the regimen was 40 tablets such as Visicol to be taken with water and bisacodyl. Subsequent regimens such as OsmoPrep with fewer tablets have been shown to be as effective and better tolerated.⁸ Microcrystalline cellulose in the tablet can produce a residue that may obscure the bowel mucosa. Newer preparations contain lower amounts of this inert ingredient, allowing for improved visualization of the colonic mucosa during colonoscopy.⁹

ADVANTAGES OF SODIUM PHOSPHATE BOWEL CLEANSERS

In a recent review article, Burke and Church¹⁰ noted that NaP cleansing regimens have been shown to be superior to PEG-electrolyte lavage solution with respect to tolerability and acceptance by patients, improved quality of bowel preparation, better mucosal visualization, and more efficient endoscopic examination. In addition, the volume of the preparation may also help decrease the risk of aspiration in some patients.^2,3

DISADVANTAGES OF SODIUM PHOSPHATE AGENTS

Despite their comparable or better efficacy and their better tolerability, NaP agents have certain disadvantages.

Effects on the colonic mucosa

In rare cases NaP agents have been shown to alter the microscopic and macroscopic features of the colonic mucosa, and they can induce aphthoid erosions that may mimic those seen in inflammatory bowel disease and enteropathy or colopathy associated with nonsteroidal anti-inflammatory drugs (NSAIDs).^11–13 Therefore, NaP agents should not be used prior to the initial endoscopic evaluation of patients with suspected inflammatory bowel disease, microscopic colitis, or NSAID-induced colonopathy.

Fluid and electrolyte shifts

Because NaP acts by drawing plasma water into the bowel lumen, significant volume and electrolyte shifts may occur.^14,15 These can cause hypokalemia, hyperphosphatemia, hypocalcemia, hyponatremia or hypernatremia, hypomagnesemia, elevated blood urea nitrogen levels, decreased exercise capacity, increased plasma osmolarity,^15–17 seizures,¹⁸ and acute renal failure with or without nephrocalcinosis.^17,19–21

Thus, patients with significant comorbidities—such as a recent history of myocardial infarction, renal or hepatic insufficiency, or malnutrition—should not use NaP agents.²²

Pivotal study of adverse events

In May 2006, the FDA issued an alert outlining the concerns of using oral NaP in specific patient populations. Of note were documented cases of acute phosphate nephropathy in 21 patients who used aqueous NaP (Fleet Phospho-Soda or Fleet Accu-Prep), and in 1 patient who used NaP tablets (Visicol).²³ Acute renal injury was not limited to patients with preexisting renal insufficiency. It is uncertain whether this means that otherwise healthy people suffered renal injury or had risk factors besides renal insufficiency, since the data cited by the FDA report do not elucidate the possible risk factors for the development of nephropathy in patients with no preexisting renal insufficiency. So far, no cases of acute phosphate nephropathy or acute renal failure have been reported with OsmoPrep, a NaP tablet bowel preparation recently approved by the FDA.²⁴ The long-term safety of OsmoPrep needs further evaluation.

PROCEED WITH CAUTION

Certain situations such as advanced age and cardiac, renal, and hepatic dysfunction call for extreme caution in the use of NaP bowel preparation agents. Therefore, it is recommended that patients with the following conditions should avoid using NaP agents for colon preparation:

• Hepatic or renal insufficiency (there are no data as to the degree of hepatic or renal insufficiency)
• Congestive heart failure
• Over age 65
• Dehydration or hypercalcemia
• Chronic use of drugs that affect renal perfusion, such as NSAIDs, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, or diuretics for hypertension.

Patients who take diuretics should not take them while they are using NaP for bowel preparation because of the risk of electrolyte abnormalities such as hypokalemia. In patients who have no alternative but to proceed with NaP preparation, our recommendation would be that the patient hold off taking diuretics, ACE inhibitors, and angiotensin receptor blockers while using the NaP prep. Given the importance of these medications in controlling diseases such as hypertension, the physician and the patient should jointly determine whether the benefits of using an NaP agent justify holding these drugs. We believe that patients taking these drugs should try using a PEG solution before considering NaP.

TASK FORCE GUIDELINES

Guidelines for using NaP bowel preparation agents, published by a task force of the American Society of Colon and Rectal Surgeons, the American Society for Gastrointestinal Endoscopy, and the Society of American Gastrointestinal and Endoscopic Surgeons,²⁵ include the following caveats:

• Aqueous and tablet NaP colonic preparations are an alternative to PEG solutions, except in pediatric populations, patients over age 65, and those with bowel obstruction or other structural intestinal disorder, gut dysmotility, renal or hepatic insufficiency, congestive heart failure, or seizure disorder.
• Dosing should be 45 mL in divided doses, 10 to 12 hours apart, with at least one dose taken on the morning of the procedure.²⁵
• The significant volume contraction and resulting dehydration seen in some patients using NaP preparations may be lessened by encouraging patients to drink fluids liberally during the days leading up to their procedure, and especially during NaP bowel preparation.²⁶
• NaP tablets should be dosed as 32 to 40 tablets. On the evening before the procedure the patient should take 20 tablets and then 12 to 20 tablets approximately 3 to 5 hours before undergoing endoscopy. The tablets should be taken four at a time every 15 minutes with approximately 8 oz of clear liquid.²⁵

Sodium phosphate (NaP) agents were introduced to provide a gentler alternative to polyethylene glycol (PEG) bowel preparations, which require patients to drink up to 4 liters of fluid over a few hours.

However, in May 2006 the US Food and Drug Administration (FDA) issued an alert that NaP products for bowel cleansing may, in some patients, pose a risk of acute phosphate nephropathy, a rare form of acute renal failure.

Although NaP preparations are generally safe and well tolerated, they can cause significant fluid shifts and electrolyte abnormalities. As such, they should not be used in patients with baseline electrolyte imbalances, renal or hepatic dysfunction, or a number of other comorbidities.

CURRENT BOWEL-CLEANSING OPTIONS

For many years the standard preparation for bowel cleansing was a 4-liter or a 2-liter PEG electrolyte solution plus a laxative (eg, magnesium citrate, bisacodyl, or senna).^1–3 The most frequent complaint heard from patients was that “the preparation is worse than the colonoscopy,” attributable to the taste and volume of the fluid they had to consume. Thus, compliance was often a significant issue with patients presenting for colonoscopy. In fact, inadequate bowel preparation is one of the most common reasons polyps are missed during colonoscopy.

Aqueous and tablet forms of NaP (sometimes with a laxative) have become a widely used alternative to PEG solutions because they require much less volume and as a result are more palatable, thereby improving compliance.^4,5

NaP agents cleanse the colon by osmotically drawing plasma water into the bowel lumen. The patient must drink significant amounts of water or other oral solutions to prevent dehydration.

NaP-based bowel-cleansing agents are available in two forms: aqueous solution and tablet. Aqueous NaP (such as Fleet Phospho-soda) is a low-volume hyperosmotic solution containing 48 g of monobasic NaP and 18 g of dibasic NaP per 100 mL.⁶ An oral tablet form (such as Visicol and OsmoPrep) was developed to improve patient tolerance.⁷ Each 2-g tablet of Visicol contains 1,500 mg of active ingredients (monobasic and dibasic NaP) and 460 mg of microcrystalline cellulose, an inert polymer. Each OsmoPrep tablet contains 1,500 mg of the same active ingredients as Visicol, but the inert ingredients include PEG and magnesium stearate.

At first, the regimen was 40 tablets such as Visicol to be taken with water and bisacodyl. Subsequent regimens such as OsmoPrep with fewer tablets have been shown to be as effective and better tolerated.⁸ Microcrystalline cellulose in the tablet can produce a residue that may obscure the bowel mucosa. Newer preparations contain lower amounts of this inert ingredient, allowing for improved visualization of the colonic mucosa during colonoscopy.⁹

ADVANTAGES OF SODIUM PHOSPHATE BOWEL CLEANSERS

In a recent review article, Burke and Church¹⁰ noted that NaP cleansing regimens have been shown to be superior to PEG-electrolyte lavage solution with respect to tolerability and acceptance by patients, improved quality of bowel preparation, better mucosal visualization, and more efficient endoscopic examination. In addition, the volume of the preparation may also help decrease the risk of aspiration in some patients.^2,3

DISADVANTAGES OF SODIUM PHOSPHATE AGENTS

Despite their comparable or better efficacy and their better tolerability, NaP agents have certain disadvantages.

Effects on the colonic mucosa

In rare cases NaP agents have been shown to alter the microscopic and macroscopic features of the colonic mucosa, and they can induce aphthoid erosions that may mimic those seen in inflammatory bowel disease and enteropathy or colopathy associated with nonsteroidal anti-inflammatory drugs (NSAIDs).^11–13 Therefore, NaP agents should not be used prior to the initial endoscopic evaluation of patients with suspected inflammatory bowel disease, microscopic colitis, or NSAID-induced colonopathy.

Fluid and electrolyte shifts

Because NaP acts by drawing plasma water into the bowel lumen, significant volume and electrolyte shifts may occur.^14,15 These can cause hypokalemia, hyperphosphatemia, hypocalcemia, hyponatremia or hypernatremia, hypomagnesemia, elevated blood urea nitrogen levels, decreased exercise capacity, increased plasma osmolarity,^15–17 seizures,¹⁸ and acute renal failure with or without nephrocalcinosis.^17,19–21

Thus, patients with significant comorbidities—such as a recent history of myocardial infarction, renal or hepatic insufficiency, or malnutrition—should not use NaP agents.²²

Pivotal study of adverse events

In May 2006, the FDA issued an alert outlining the concerns of using oral NaP in specific patient populations. Of note were documented cases of acute phosphate nephropathy in 21 patients who used aqueous NaP (Fleet Phospho-Soda or Fleet Accu-Prep), and in 1 patient who used NaP tablets (Visicol).²³ Acute renal injury was not limited to patients with preexisting renal insufficiency. It is uncertain whether this means that otherwise healthy people suffered renal injury or had risk factors besides renal insufficiency, since the data cited by the FDA report do not elucidate the possible risk factors for the development of nephropathy in patients with no preexisting renal insufficiency. So far, no cases of acute phosphate nephropathy or acute renal failure have been reported with OsmoPrep, a NaP tablet bowel preparation recently approved by the FDA.²⁴ The long-term safety of OsmoPrep needs further evaluation.

PROCEED WITH CAUTION

Certain situations such as advanced age and cardiac, renal, and hepatic dysfunction call for extreme caution in the use of NaP bowel preparation agents. Therefore, it is recommended that patients with the following conditions should avoid using NaP agents for colon preparation:

• Hepatic or renal insufficiency (there are no data as to the degree of hepatic or renal insufficiency)
• Congestive heart failure
• Over age 65
• Dehydration or hypercalcemia
• Chronic use of drugs that affect renal perfusion, such as NSAIDs, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, or diuretics for hypertension.

Patients who take diuretics should not take them while they are using NaP for bowel preparation because of the risk of electrolyte abnormalities such as hypokalemia. In patients who have no alternative but to proceed with NaP preparation, our recommendation would be that the patient hold off taking diuretics, ACE inhibitors, and angiotensin receptor blockers while using the NaP prep. Given the importance of these medications in controlling diseases such as hypertension, the physician and the patient should jointly determine whether the benefits of using an NaP agent justify holding these drugs. We believe that patients taking these drugs should try using a PEG solution before considering NaP.

TASK FORCE GUIDELINES

Guidelines for using NaP bowel preparation agents, published by a task force of the American Society of Colon and Rectal Surgeons, the American Society for Gastrointestinal Endoscopy, and the Society of American Gastrointestinal and Endoscopic Surgeons,²⁵ include the following caveats:

• Aqueous and tablet NaP colonic preparations are an alternative to PEG solutions, except in pediatric populations, patients over age 65, and those with bowel obstruction or other structural intestinal disorder, gut dysmotility, renal or hepatic insufficiency, congestive heart failure, or seizure disorder.
• Dosing should be 45 mL in divided doses, 10 to 12 hours apart, with at least one dose taken on the morning of the procedure.²⁵
• The significant volume contraction and resulting dehydration seen in some patients using NaP preparations may be lessened by encouraging patients to drink fluids liberally during the days leading up to their procedure, and especially during NaP bowel preparation.²⁶
• NaP tablets should be dosed as 32 to 40 tablets. On the evening before the procedure the patient should take 20 tablets and then 12 to 20 tablets approximately 3 to 5 hours before undergoing endoscopy. The tablets should be taken four at a time every 15 minutes with approximately 8 oz of clear liquid.²⁵