Amy Rothman Schonfeld

CHICAGO — Up to 20% of strokes begin in the heart, so cardiac imaging should be part of the work-up of many stroke patients, Dr. Gautham Reddy said at the annual meeting of the American Society of Neuroradiology.

Electrocardiographically gated multidetector CT can assess the brain, cerebral vessels, and carotid arteries as well as the heart simultaneously and expedite diagnosis, he said.

At the University of California, San Francisco, where Dr. Reddy is chief of cardiac and pulmonary imaging, stroke patients are routinely scanned from the head down to the heart. Other modalities such as transthoracic or transesophageal echocardiography or MRI may be superior for evaluating cardiac masses, cardiomyopathy, or ischemic heart disease, but the ability to obtain a comprehensive evaluation from one sitting using CT can be advantageous for both the patient and physician—especially in the emergency setting.

The most common cardiac source of stroke is emboli, Dr. Reddy said. One such patient, diagnosed using multidetector CT, who had a history of atrial fibrillation and had been on anticoagulation, decided to stop taking his medication, then developed a stroke caused by a thrombus originating in the left atrium. Mitral stenosis is another common source of cardiac thrombus from the atrium.

Coagulation disorders and aneurysms may cause cardiac thrombi that originate in the ventricles. Left ventricular aneurysms may follow myocardial infarction and can be categorized as either true or false aneurysms.

True aneurysms characteristically have an anteroapical location with a wide ostium (greater than 50% of the aneurysm diameter). In contrast, false aneurysms are postdiaphragmatic with narrow ostia. Accurate and rapid diagnosis can have an impact on treatment, because true aneurysms are generally managed medically while false aneurysms require resection.

Cardiac tumors can also embolize to the brain. According to Dr. Reddy, about 98% of cardiac tumors are metastases from another source. Of primary cardiac tumors, myxomas, which are benign, are the most common and most likely to produce brain emboli. In fact, avoiding brain emboli is one of the major reasons for myxoma resection. Primary malignant tumors of the heart, such as angiosarcomas, also have the potential to embolize and cause stroke, as can secondary tumors such as lymphoma.

Cardiac imaging also can reveal the presence of patent foramen ovale or other septal defects in patients with strokes. These openings allow a clot or tumor to pass from the right side to the left side of the heart, and then enter the arterial circulation as a paradoxical embolism. Repair of even small defects may be recommended to avoid subsequent strokes, Dr. Reddy said.

Reconstructed coronal imaging shows a thrombus in the left atrial appendage.

The arrow shows a thrombus in a true aneurysm of the left ventricle.

A false aneurysm in the postero-inferior aspect of the LV is reconstructed on CT. Photos courtesy Dr. Gautham Reddy

CHICAGO — Up to 20% of strokes begin in the heart, so cardiac imaging should be part of the work-up of many stroke patients, Dr. Gautham Reddy said at the annual meeting of the American Society of Neuroradiology.

Electrocardiographically gated multidetector CT can assess the brain, cerebral vessels, and carotid arteries as well as the heart simultaneously and expedite diagnosis, he said.

At the University of California, San Francisco, where Dr. Reddy is chief of cardiac and pulmonary imaging, stroke patients are routinely scanned from the head down to the heart. Other modalities such as transthoracic or transesophageal echocardiography or MRI may be superior for evaluating cardiac masses, cardiomyopathy, or ischemic heart disease, but the ability to obtain a comprehensive evaluation from one sitting using CT can be advantageous for both the patient and physician—especially in the emergency setting.

The most common cardiac source of stroke is emboli, Dr. Reddy said. One such patient, diagnosed using multidetector CT, who had a history of atrial fibrillation and had been on anticoagulation, decided to stop taking his medication, then developed a stroke caused by a thrombus originating in the left atrium. Mitral stenosis is another common source of cardiac thrombus from the atrium.

Coagulation disorders and aneurysms may cause cardiac thrombi that originate in the ventricles. Left ventricular aneurysms may follow myocardial infarction and can be categorized as either true or false aneurysms.

True aneurysms characteristically have an anteroapical location with a wide ostium (greater than 50% of the aneurysm diameter). In contrast, false aneurysms are postdiaphragmatic with narrow ostia. Accurate and rapid diagnosis can have an impact on treatment, because true aneurysms are generally managed medically while false aneurysms require resection.

Cardiac tumors can also embolize to the brain. According to Dr. Reddy, about 98% of cardiac tumors are metastases from another source. Of primary cardiac tumors, myxomas, which are benign, are the most common and most likely to produce brain emboli. In fact, avoiding brain emboli is one of the major reasons for myxoma resection. Primary malignant tumors of the heart, such as angiosarcomas, also have the potential to embolize and cause stroke, as can secondary tumors such as lymphoma.

Cardiac imaging also can reveal the presence of patent foramen ovale or other septal defects in patients with strokes. These openings allow a clot or tumor to pass from the right side to the left side of the heart, and then enter the arterial circulation as a paradoxical embolism. Repair of even small defects may be recommended to avoid subsequent strokes, Dr. Reddy said.

Reconstructed coronal imaging shows a thrombus in the left atrial appendage.

The arrow shows a thrombus in a true aneurysm of the left ventricle.

A false aneurysm in the postero-inferior aspect of the LV is reconstructed on CT. Photos courtesy Dr. Gautham Reddy

CHICAGO — Up to 20% of strokes begin in the heart, so cardiac imaging should be part of the work-up of many stroke patients, Dr. Gautham Reddy said at the annual meeting of the American Society of Neuroradiology.

Electrocardiographically gated multidetector CT can assess the brain, cerebral vessels, and carotid arteries as well as the heart simultaneously and expedite diagnosis, he said.

At the University of California, San Francisco, where Dr. Reddy is chief of cardiac and pulmonary imaging, stroke patients are routinely scanned from the head down to the heart. Other modalities such as transthoracic or transesophageal echocardiography or MRI may be superior for evaluating cardiac masses, cardiomyopathy, or ischemic heart disease, but the ability to obtain a comprehensive evaluation from one sitting using CT can be advantageous for both the patient and physician—especially in the emergency setting.

The most common cardiac source of stroke is emboli, Dr. Reddy said. One such patient, diagnosed using multidetector CT, who had a history of atrial fibrillation and had been on anticoagulation, decided to stop taking his medication, then developed a stroke caused by a thrombus originating in the left atrium. Mitral stenosis is another common source of cardiac thrombus from the atrium.

Coagulation disorders and aneurysms may cause cardiac thrombi that originate in the ventricles. Left ventricular aneurysms may follow myocardial infarction and can be categorized as either true or false aneurysms.

True aneurysms characteristically have an anteroapical location with a wide ostium (greater than 50% of the aneurysm diameter). In contrast, false aneurysms are postdiaphragmatic with narrow ostia. Accurate and rapid diagnosis can have an impact on treatment, because true aneurysms are generally managed medically while false aneurysms require resection.

Cardiac tumors can also embolize to the brain. According to Dr. Reddy, about 98% of cardiac tumors are metastases from another source. Of primary cardiac tumors, myxomas, which are benign, are the most common and most likely to produce brain emboli. In fact, avoiding brain emboli is one of the major reasons for myxoma resection. Primary malignant tumors of the heart, such as angiosarcomas, also have the potential to embolize and cause stroke, as can secondary tumors such as lymphoma.

Cardiac imaging also can reveal the presence of patent foramen ovale or other septal defects in patients with strokes. These openings allow a clot or tumor to pass from the right side to the left side of the heart, and then enter the arterial circulation as a paradoxical embolism. Repair of even small defects may be recommended to avoid subsequent strokes, Dr. Reddy said.

Reconstructed coronal imaging shows a thrombus in the left atrial appendage.

The arrow shows a thrombus in a true aneurysm of the left ventricle.

A false aneurysm in the postero-inferior aspect of the LV is reconstructed on CT. Photos courtesy Dr. Gautham Reddy

CHICAGO — Patients with symptomatic intracranial atherosclerosis can be treated successfully and with a relatively low rate of procedural complications with a new stent system designed specifically for this indication, according to Dr. Aquilla Turk, who presented his findings at the annual meeting of the American Society of Neuroradiology.

The stent system provides patients who have medically refractory atherosclerotic stenosis with a new treatment option other than medical therapy.

Over a 1-year period, 134 symptomatic patients (average age 63.2 years, 59% male) with 142 lesions underwent angioplasty and stenting with the Gateway balloon- Wingspan stent system. The Wingspan is a flexible, self-expanding, microcatheter-delivered microstent that is manufactured by Boston Scientific Corp. (Natick, Mass.).

About 57% of the patients presented initially with a stroke. At baseline, the average stenosis was 75%. After angioplasty with the balloon, average stenosis fell to 43% and then dropped to 28% upon stent placement, said Dr. Turk, a radiologist affiliated with the University of Wisconsin, Madison.

Dr. Turk is one of the investigators from five different centers who is participating in the Neuroendovascular Research Collaboration.

Stents were placed with a 98% first-session success rate. Treated lesions were located in the internal carotid (46 lesions) and the vertebral (29 lesions), basilar (30 lesions), and middle cerebral (37 lesions) arteries.

The periprocedural stroke and death rate was 4.9%, which compares favorably with that of angioplasty alone, said Dr. Turk.

Two-thirds of the patients (88) were followed for 3–6 months. Of these 88 patients, 10 had other events, of which 4 were attributed to antiplatelet medication discontinuation, either because of patient noncompliance or because of other physician's orders.

Imaging follow-up was available for 90 lesions. Of those lesions, 32 demonstrated in-stent restenosis or occlusion, and 10 were symptomatic.

Of the 10 patients who had symptomatic restenosis, only 2 went on to have subsequent stroke or died.

Eleven of the 32 lesions were retreated, and in-stent dissections were discovered in three of these patients. Two of the dissections required placement of an additional Wingspan stent and one patient had a reperfusion hemorrhage after retreatment.

“Intracranial atherosclerosis accounts for about 40,000–60,000 cases of new stroke reported in the U.S. each year,” said Dr. Turk, who noted that “an acceptable surgical therapy has not been found.”

The Wingspan registry is funded by an unrestricted grant from Boston Scientific. Dr. Turk is a researcher and consultant for Boston Scientific.

Significant stenosis of the right middle cerebral artery is seen with abnormally long transit time.

Imaging shows right middle cerebral artery normalization following stenting with the Wingspan system. Photos courtesy Dr. Aquilla Turk

CHICAGO — Patients with symptomatic intracranial atherosclerosis can be treated successfully and with a relatively low rate of procedural complications with a new stent system designed specifically for this indication, according to Dr. Aquilla Turk, who presented his findings at the annual meeting of the American Society of Neuroradiology.

The stent system provides patients who have medically refractory atherosclerotic stenosis with a new treatment option other than medical therapy.

Over a 1-year period, 134 symptomatic patients (average age 63.2 years, 59% male) with 142 lesions underwent angioplasty and stenting with the Gateway balloon- Wingspan stent system. The Wingspan is a flexible, self-expanding, microcatheter-delivered microstent that is manufactured by Boston Scientific Corp. (Natick, Mass.).

About 57% of the patients presented initially with a stroke. At baseline, the average stenosis was 75%. After angioplasty with the balloon, average stenosis fell to 43% and then dropped to 28% upon stent placement, said Dr. Turk, a radiologist affiliated with the University of Wisconsin, Madison.

Dr. Turk is one of the investigators from five different centers who is participating in the Neuroendovascular Research Collaboration.

Stents were placed with a 98% first-session success rate. Treated lesions were located in the internal carotid (46 lesions) and the vertebral (29 lesions), basilar (30 lesions), and middle cerebral (37 lesions) arteries.

The periprocedural stroke and death rate was 4.9%, which compares favorably with that of angioplasty alone, said Dr. Turk.

Two-thirds of the patients (88) were followed for 3–6 months. Of these 88 patients, 10 had other events, of which 4 were attributed to antiplatelet medication discontinuation, either because of patient noncompliance or because of other physician's orders.

Imaging follow-up was available for 90 lesions. Of those lesions, 32 demonstrated in-stent restenosis or occlusion, and 10 were symptomatic.

Of the 10 patients who had symptomatic restenosis, only 2 went on to have subsequent stroke or died.

Eleven of the 32 lesions were retreated, and in-stent dissections were discovered in three of these patients. Two of the dissections required placement of an additional Wingspan stent and one patient had a reperfusion hemorrhage after retreatment.

“Intracranial atherosclerosis accounts for about 40,000–60,000 cases of new stroke reported in the U.S. each year,” said Dr. Turk, who noted that “an acceptable surgical therapy has not been found.”

The Wingspan registry is funded by an unrestricted grant from Boston Scientific. Dr. Turk is a researcher and consultant for Boston Scientific.

Significant stenosis of the right middle cerebral artery is seen with abnormally long transit time.

Imaging shows right middle cerebral artery normalization following stenting with the Wingspan system. Photos courtesy Dr. Aquilla Turk

CHICAGO — Patients with symptomatic intracranial atherosclerosis can be treated successfully and with a relatively low rate of procedural complications with a new stent system designed specifically for this indication, according to Dr. Aquilla Turk, who presented his findings at the annual meeting of the American Society of Neuroradiology.

The stent system provides patients who have medically refractory atherosclerotic stenosis with a new treatment option other than medical therapy.

Over a 1-year period, 134 symptomatic patients (average age 63.2 years, 59% male) with 142 lesions underwent angioplasty and stenting with the Gateway balloon- Wingspan stent system. The Wingspan is a flexible, self-expanding, microcatheter-delivered microstent that is manufactured by Boston Scientific Corp. (Natick, Mass.).

About 57% of the patients presented initially with a stroke. At baseline, the average stenosis was 75%. After angioplasty with the balloon, average stenosis fell to 43% and then dropped to 28% upon stent placement, said Dr. Turk, a radiologist affiliated with the University of Wisconsin, Madison.

Dr. Turk is one of the investigators from five different centers who is participating in the Neuroendovascular Research Collaboration.

Stents were placed with a 98% first-session success rate. Treated lesions were located in the internal carotid (46 lesions) and the vertebral (29 lesions), basilar (30 lesions), and middle cerebral (37 lesions) arteries.

The periprocedural stroke and death rate was 4.9%, which compares favorably with that of angioplasty alone, said Dr. Turk.

Two-thirds of the patients (88) were followed for 3–6 months. Of these 88 patients, 10 had other events, of which 4 were attributed to antiplatelet medication discontinuation, either because of patient noncompliance or because of other physician's orders.

Imaging follow-up was available for 90 lesions. Of those lesions, 32 demonstrated in-stent restenosis or occlusion, and 10 were symptomatic.

Of the 10 patients who had symptomatic restenosis, only 2 went on to have subsequent stroke or died.

Eleven of the 32 lesions were retreated, and in-stent dissections were discovered in three of these patients. Two of the dissections required placement of an additional Wingspan stent and one patient had a reperfusion hemorrhage after retreatment.

“Intracranial atherosclerosis accounts for about 40,000–60,000 cases of new stroke reported in the U.S. each year,” said Dr. Turk, who noted that “an acceptable surgical therapy has not been found.”

The Wingspan registry is funded by an unrestricted grant from Boston Scientific. Dr. Turk is a researcher and consultant for Boston Scientific.

Significant stenosis of the right middle cerebral artery is seen with abnormally long transit time.

Imaging shows right middle cerebral artery normalization following stenting with the Wingspan system. Photos courtesy Dr. Aquilla Turk

CHICAGO — Radiologic professional associations and governmental regulatory agencies in the United States and Europe are in the midst of grappling with how best to deal with nephrogenic systemic fibrosis, a severe scleroderma-like syndrome that may arise in patients with poor kidney function after receiving gadolinium-based contrast agents administered during magnetic resonance imaging.

This problem necessitates practice changes, including restrictions on contrast magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) in patients with moderate- to end-stage renal disease, attention to new, stricter screening recommendations, and foregoing sensitive studies that rely on high doses of contrast agents, according to Dr. Emanuel Kanal, who spoke at the American Society of Neuroradiology meeting.

"This has taken the world by storm," said Dr. Kanal, a neuroradiologist at the University of Pittsburgh, who has received hundreds of e-mails from concerned physicians. New developments are occurring almost daily. For instance, on June 22, the American College of Radiology Committees on Drugs and Contrast Media and MR Safety discussed recommendations for screening patients before contrast-enhanced MRI that go beyond verbal questioning.

Although final recommendations have not yet been issued, it is expected that plasma blood screening to assess glomerular filtration rates (GFRs) will be recommended before contrast-enhanced MRI for patients at risk.

Within the same week, on June 26:

▸ A European regulatory body representing 31 members of the European Union (the European Pharmacovigilance Working Party of the Committee for Medicinal Products for Human Use) added the gadolinium-based contrast agent Magnevist to the list of contraindicated drugs for patients with severe and end-stage renal disease.

▸ The Chairman of the Commission on Human Medicines in the United Kingdom, Sir Gordon Duff, released a "Dear Colleague" letter with similar content.

▸ The European Update issued a statement that "a review of the available data does not suggest that the risk of NSF in patients with advanced renal impairment is the same for all gadolinium-based contrast agents"–the first time any formal society or agency other than the American College of Radiology has arrived at that conclusion, Dr. Kanal said.

Nephrogenic systemic fibrosis (NSF) is a scleroderma/myxoderma-like condition that causes painful scarring, tightening, thickening, and discoloration of the skin. It also affects the lungs, myocardium, diaphragm, and striated muscle.

NSF can be debilitating and fulminant in about 5% of cases and can lead to immobility and death within weeks to months. There is no known cure, with occasional improvement noted following renal transplantation.

In 2006, Dr. Thomas Grobner, a nephrologist at the General Hospital of Wiener Neustadt, Austria, made the first association between gadolinium and NSF (Nephrol. Dial. Transplant. 2006 Oct. 11;E-pub ahead of print). Since then, more than 240 confirmed cases have been included in a registry maintained by Dr. Shawn Cowper, a dermatopathologist at Yale University, New Haven, Conn., who found that all affected patients had received gadolinium contrast agents within a few months before diagnosis.

Of the over 230 cases of NSF that have been reported to the Food and Drug Administration's MedWatch up until April 17 of this year, 160 were related to Omniscan and 73 to Magnevist, with 3 associated with isolated prior Optimark administration.

Gadolinium concentrations in the biopsies of NSF patients were 35 to 150 times higher than those found in normal volunteers who received contrast material, Dr. Kanal said. Although the half-life of gadolinium is 70-90 minutes in those with normal renal function, gadolinium has been detected in tissue biopsy specimens of NSF patients as long as 11 months after administration.

Clinical data suggest several associations that impact clinical practice:

▸ The higher the dose of contrast, the greater the chance of developing NSF.

▸ The greater the severity of renal disease, the greater the chance of developing NSF.

▸ Cumulative doses of contrast seem to increase the incidence of NSF.

These findings can have a significant impact on clinical practice. For instance, MRI studies that use double or triple doses of contrast, such as contrast dynamic bolus MRA, may no longer be an option for patients with severely impaired renal function. Alternatively, the radiologist may modify the study to minimize the administered dose of gadolinium-based contrast agent.

The spike in NSF cases in recent years is directly related to the more common use of high-dose contrast studies since the proliferation of especially non-neuroradiologic contrast bolus dynamic MR angiography in the mid-1990s, Dr. Kanal suggested.

"With iodinated contrast-related [contrast-induced nephropathy] concerns for CT and NSF-related concerns for gadolinium-based MR contrast agents in MRI, this is becoming a problem for neurologists and other referring physicians, as the number of imaging tests available for patients with severe renal disease that can sensitively evaluate problems is decreasing," he said.

Patients with stage III kidney disease or worse should not routinely be administered standard doses of gadolinium-based MR contrast agents, he recommended. This can have serious implications for the 35 million U.S. adults over age 65 years who have stage III or IV renal disease, many of whom require access to diagnostic MR services, Dr. Kanal said.

Exacerbating the problem is poor patient awareness of renal disease. According to Dr. Kanal, 97% of women and 82% of men with stage III chronic kidney disease are unaware that they have it. Thus asking patients whether they have renal disease may no longer be a sufficient screening method.

It is anticipated that a subset of patients at risk for renal disease (over age 60 years, history of hypertension, diabetes, renal disease or severe hepatic disease) will be required to have their glomerular filtration rates assessed before receiving gadolinium-based MR contrast agents. Since the risk of NSF may increase with cumulative dosing, neurologists should carefully consider the potential risk of serial contrast-enhanced scans when following patients.

While the FDA has applied black box warnings to all five MR contrast agents available in the United States, "the available data 'screams' that [the risk of NSF] is not equal for all the five FDA-approved MR contrast agents, and appears to be higher or far higher for Omniscan," he said, estimating that roughly 3%-7% of patients with end-stage renal disease receiving high-dose Omniscan will develop NSF.

"In my opinion, the present data are sufficiently compelling to avoid Omniscan administration in patients with any significant level of renal disease," he added.

For gadolinium to be tolerated by humans, it must be chelated to a ligand molecule, he said. The likelihood of the ligand dissociating from the gadolinium ion (leaving the toxic free Gd+3) is far from equal among these five agents, being far greater in Omniscan and Optimark than in Magnevist, Multihance, or Prohance, judging from findings from in vitro and some in vivo studies. Because nonionic Omniscan and Optimark have a far lower conditional stability constant than do Magnevist, Multihance, and Prohance at normal body pH, it is possible that this may be related to the perceived greater incidence of NSF in patients who received Omniscan, Dr. Kanal said.

Elevated levels of calcium, phosphate, copper, iron, and zinc, which can compete with the gadolinium ion for coupling with the ligand molecule, may also exacerbate the risk of toxicity.

"You need a radiologist who knows what she or he is doing in this area to help design the study in a manner that will decrease dosing yet still be as diagnostic as possible. Trust your radiologist and then follow his feedback and guidance," he commented.

If a dialysis patient must have a contrast MRI, the American College of Radiology guidelines recommend that the patient be taken to hemodialysis immediately following the completion of the MR examination in which the gadolinium-based MR contrast agent had been administered. Radiologists should compile a database of all patients with stage III or more severe kidney disease who have had contrast-enhanced MRIs and follow them to ensure that they do not develop NSF, Dr. Kanal recommended.

"It used to be that patients with renal failure would specifically be sent to MR because the contrast agents were not directly nephrotoxic at the doses used, whereas giving iodine to patients with renal disease could cause iodine-induced nephropathy. Now we have something else to worry about for patients with renal disease: NSF," Dr. Kanal said.

Patients with stage IIIkidney disease or worse shouldn't be routinely given standard doses of gadolinium-based agents. DR. KANAL

The skin on the arm of a patient with contrast agent-induced nephrogenic systemic fibrosis shows scleroderma-like changes, including scarring (which is usually painful), tightening, thickening, and discoloration. Nephrogenic systemic fibrosis is fulminant in about 5% of cases and can prove to be fatal within weeks. Courtesy Dr. Shawn Cowper

CHICAGO — Radiologic professional associations and governmental regulatory agencies in the United States and Europe are in the midst of grappling with how best to deal with nephrogenic systemic fibrosis, a severe scleroderma-like syndrome that may arise in patients with poor kidney function after receiving gadolinium-based contrast agents administered during magnetic resonance imaging.

This problem necessitates practice changes, including restrictions on contrast magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) in patients with moderate- to end-stage renal disease, attention to new, stricter screening recommendations, and foregoing sensitive studies that rely on high doses of contrast agents, according to Dr. Emanuel Kanal, who spoke at the American Society of Neuroradiology meeting.

"This has taken the world by storm," said Dr. Kanal, a neuroradiologist at the University of Pittsburgh, who has received hundreds of e-mails from concerned physicians. New developments are occurring almost daily. For instance, on June 22, the American College of Radiology Committees on Drugs and Contrast Media and MR Safety discussed recommendations for screening patients before contrast-enhanced MRI that go beyond verbal questioning.

Although final recommendations have not yet been issued, it is expected that plasma blood screening to assess glomerular filtration rates (GFRs) will be recommended before contrast-enhanced MRI for patients at risk.

Within the same week, on June 26:

▸ A European regulatory body representing 31 members of the European Union (the European Pharmacovigilance Working Party of the Committee for Medicinal Products for Human Use) added the gadolinium-based contrast agent Magnevist to the list of contraindicated drugs for patients with severe and end-stage renal disease.

▸ The Chairman of the Commission on Human Medicines in the United Kingdom, Sir Gordon Duff, released a "Dear Colleague" letter with similar content.

▸ The European Update issued a statement that "a review of the available data does not suggest that the risk of NSF in patients with advanced renal impairment is the same for all gadolinium-based contrast agents"–the first time any formal society or agency other than the American College of Radiology has arrived at that conclusion, Dr. Kanal said.

Nephrogenic systemic fibrosis (NSF) is a scleroderma/myxoderma-like condition that causes painful scarring, tightening, thickening, and discoloration of the skin. It also affects the lungs, myocardium, diaphragm, and striated muscle.

NSF can be debilitating and fulminant in about 5% of cases and can lead to immobility and death within weeks to months. There is no known cure, with occasional improvement noted following renal transplantation.

In 2006, Dr. Thomas Grobner, a nephrologist at the General Hospital of Wiener Neustadt, Austria, made the first association between gadolinium and NSF (Nephrol. Dial. Transplant. 2006 Oct. 11;E-pub ahead of print). Since then, more than 240 confirmed cases have been included in a registry maintained by Dr. Shawn Cowper, a dermatopathologist at Yale University, New Haven, Conn., who found that all affected patients had received gadolinium contrast agents within a few months before diagnosis.

Of the over 230 cases of NSF that have been reported to the Food and Drug Administration's MedWatch up until April 17 of this year, 160 were related to Omniscan and 73 to Magnevist, with 3 associated with isolated prior Optimark administration.

Gadolinium concentrations in the biopsies of NSF patients were 35 to 150 times higher than those found in normal volunteers who received contrast material, Dr. Kanal said. Although the half-life of gadolinium is 70-90 minutes in those with normal renal function, gadolinium has been detected in tissue biopsy specimens of NSF patients as long as 11 months after administration.

Clinical data suggest several associations that impact clinical practice:

▸ The higher the dose of contrast, the greater the chance of developing NSF.

▸ The greater the severity of renal disease, the greater the chance of developing NSF.

▸ Cumulative doses of contrast seem to increase the incidence of NSF.

These findings can have a significant impact on clinical practice. For instance, MRI studies that use double or triple doses of contrast, such as contrast dynamic bolus MRA, may no longer be an option for patients with severely impaired renal function. Alternatively, the radiologist may modify the study to minimize the administered dose of gadolinium-based contrast agent.

The spike in NSF cases in recent years is directly related to the more common use of high-dose contrast studies since the proliferation of especially non-neuroradiologic contrast bolus dynamic MR angiography in the mid-1990s, Dr. Kanal suggested.

"With iodinated contrast-related [contrast-induced nephropathy] concerns for CT and NSF-related concerns for gadolinium-based MR contrast agents in MRI, this is becoming a problem for neurologists and other referring physicians, as the number of imaging tests available for patients with severe renal disease that can sensitively evaluate problems is decreasing," he said.

Patients with stage III kidney disease or worse should not routinely be administered standard doses of gadolinium-based MR contrast agents, he recommended. This can have serious implications for the 35 million U.S. adults over age 65 years who have stage III or IV renal disease, many of whom require access to diagnostic MR services, Dr. Kanal said.

Exacerbating the problem is poor patient awareness of renal disease. According to Dr. Kanal, 97% of women and 82% of men with stage III chronic kidney disease are unaware that they have it. Thus asking patients whether they have renal disease may no longer be a sufficient screening method.

It is anticipated that a subset of patients at risk for renal disease (over age 60 years, history of hypertension, diabetes, renal disease or severe hepatic disease) will be required to have their glomerular filtration rates assessed before receiving gadolinium-based MR contrast agents. Since the risk of NSF may increase with cumulative dosing, neurologists should carefully consider the potential risk of serial contrast-enhanced scans when following patients.

While the FDA has applied black box warnings to all five MR contrast agents available in the United States, "the available data 'screams' that [the risk of NSF] is not equal for all the five FDA-approved MR contrast agents, and appears to be higher or far higher for Omniscan," he said, estimating that roughly 3%-7% of patients with end-stage renal disease receiving high-dose Omniscan will develop NSF.

"In my opinion, the present data are sufficiently compelling to avoid Omniscan administration in patients with any significant level of renal disease," he added.

For gadolinium to be tolerated by humans, it must be chelated to a ligand molecule, he said. The likelihood of the ligand dissociating from the gadolinium ion (leaving the toxic free Gd+3) is far from equal among these five agents, being far greater in Omniscan and Optimark than in Magnevist, Multihance, or Prohance, judging from findings from in vitro and some in vivo studies. Because nonionic Omniscan and Optimark have a far lower conditional stability constant than do Magnevist, Multihance, and Prohance at normal body pH, it is possible that this may be related to the perceived greater incidence of NSF in patients who received Omniscan, Dr. Kanal said.

Elevated levels of calcium, phosphate, copper, iron, and zinc, which can compete with the gadolinium ion for coupling with the ligand molecule, may also exacerbate the risk of toxicity.

"You need a radiologist who knows what she or he is doing in this area to help design the study in a manner that will decrease dosing yet still be as diagnostic as possible. Trust your radiologist and then follow his feedback and guidance," he commented.

If a dialysis patient must have a contrast MRI, the American College of Radiology guidelines recommend that the patient be taken to hemodialysis immediately following the completion of the MR examination in which the gadolinium-based MR contrast agent had been administered. Radiologists should compile a database of all patients with stage III or more severe kidney disease who have had contrast-enhanced MRIs and follow them to ensure that they do not develop NSF, Dr. Kanal recommended.

"It used to be that patients with renal failure would specifically be sent to MR because the contrast agents were not directly nephrotoxic at the doses used, whereas giving iodine to patients with renal disease could cause iodine-induced nephropathy. Now we have something else to worry about for patients with renal disease: NSF," Dr. Kanal said.

Patients with stage IIIkidney disease or worse shouldn't be routinely given standard doses of gadolinium-based agents. DR. KANAL

The skin on the arm of a patient with contrast agent-induced nephrogenic systemic fibrosis shows scleroderma-like changes, including scarring (which is usually painful), tightening, thickening, and discoloration. Nephrogenic systemic fibrosis is fulminant in about 5% of cases and can prove to be fatal within weeks. Courtesy Dr. Shawn Cowper

CHICAGO — Radiologic professional associations and governmental regulatory agencies in the United States and Europe are in the midst of grappling with how best to deal with nephrogenic systemic fibrosis, a severe scleroderma-like syndrome that may arise in patients with poor kidney function after receiving gadolinium-based contrast agents administered during magnetic resonance imaging.

This problem necessitates practice changes, including restrictions on contrast magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) in patients with moderate- to end-stage renal disease, attention to new, stricter screening recommendations, and foregoing sensitive studies that rely on high doses of contrast agents, according to Dr. Emanuel Kanal, who spoke at the American Society of Neuroradiology meeting.

"This has taken the world by storm," said Dr. Kanal, a neuroradiologist at the University of Pittsburgh, who has received hundreds of e-mails from concerned physicians. New developments are occurring almost daily. For instance, on June 22, the American College of Radiology Committees on Drugs and Contrast Media and MR Safety discussed recommendations for screening patients before contrast-enhanced MRI that go beyond verbal questioning.

Although final recommendations have not yet been issued, it is expected that plasma blood screening to assess glomerular filtration rates (GFRs) will be recommended before contrast-enhanced MRI for patients at risk.

Within the same week, on June 26:

▸ A European regulatory body representing 31 members of the European Union (the European Pharmacovigilance Working Party of the Committee for Medicinal Products for Human Use) added the gadolinium-based contrast agent Magnevist to the list of contraindicated drugs for patients with severe and end-stage renal disease.

▸ The Chairman of the Commission on Human Medicines in the United Kingdom, Sir Gordon Duff, released a "Dear Colleague" letter with similar content.

▸ The European Update issued a statement that "a review of the available data does not suggest that the risk of NSF in patients with advanced renal impairment is the same for all gadolinium-based contrast agents"–the first time any formal society or agency other than the American College of Radiology has arrived at that conclusion, Dr. Kanal said.

Nephrogenic systemic fibrosis (NSF) is a scleroderma/myxoderma-like condition that causes painful scarring, tightening, thickening, and discoloration of the skin. It also affects the lungs, myocardium, diaphragm, and striated muscle.

NSF can be debilitating and fulminant in about 5% of cases and can lead to immobility and death within weeks to months. There is no known cure, with occasional improvement noted following renal transplantation.

In 2006, Dr. Thomas Grobner, a nephrologist at the General Hospital of Wiener Neustadt, Austria, made the first association between gadolinium and NSF (Nephrol. Dial. Transplant. 2006 Oct. 11;E-pub ahead of print). Since then, more than 240 confirmed cases have been included in a registry maintained by Dr. Shawn Cowper, a dermatopathologist at Yale University, New Haven, Conn., who found that all affected patients had received gadolinium contrast agents within a few months before diagnosis.

Of the over 230 cases of NSF that have been reported to the Food and Drug Administration's MedWatch up until April 17 of this year, 160 were related to Omniscan and 73 to Magnevist, with 3 associated with isolated prior Optimark administration.

Gadolinium concentrations in the biopsies of NSF patients were 35 to 150 times higher than those found in normal volunteers who received contrast material, Dr. Kanal said. Although the half-life of gadolinium is 70-90 minutes in those with normal renal function, gadolinium has been detected in tissue biopsy specimens of NSF patients as long as 11 months after administration.

Clinical data suggest several associations that impact clinical practice:

▸ The higher the dose of contrast, the greater the chance of developing NSF.

▸ The greater the severity of renal disease, the greater the chance of developing NSF.

▸ Cumulative doses of contrast seem to increase the incidence of NSF.

These findings can have a significant impact on clinical practice. For instance, MRI studies that use double or triple doses of contrast, such as contrast dynamic bolus MRA, may no longer be an option for patients with severely impaired renal function. Alternatively, the radiologist may modify the study to minimize the administered dose of gadolinium-based contrast agent.

The spike in NSF cases in recent years is directly related to the more common use of high-dose contrast studies since the proliferation of especially non-neuroradiologic contrast bolus dynamic MR angiography in the mid-1990s, Dr. Kanal suggested.

"With iodinated contrast-related [contrast-induced nephropathy] concerns for CT and NSF-related concerns for gadolinium-based MR contrast agents in MRI, this is becoming a problem for neurologists and other referring physicians, as the number of imaging tests available for patients with severe renal disease that can sensitively evaluate problems is decreasing," he said.

Patients with stage III kidney disease or worse should not routinely be administered standard doses of gadolinium-based MR contrast agents, he recommended. This can have serious implications for the 35 million U.S. adults over age 65 years who have stage III or IV renal disease, many of whom require access to diagnostic MR services, Dr. Kanal said.

Exacerbating the problem is poor patient awareness of renal disease. According to Dr. Kanal, 97% of women and 82% of men with stage III chronic kidney disease are unaware that they have it. Thus asking patients whether they have renal disease may no longer be a sufficient screening method.

It is anticipated that a subset of patients at risk for renal disease (over age 60 years, history of hypertension, diabetes, renal disease or severe hepatic disease) will be required to have their glomerular filtration rates assessed before receiving gadolinium-based MR contrast agents. Since the risk of NSF may increase with cumulative dosing, neurologists should carefully consider the potential risk of serial contrast-enhanced scans when following patients.

While the FDA has applied black box warnings to all five MR contrast agents available in the United States, "the available data 'screams' that [the risk of NSF] is not equal for all the five FDA-approved MR contrast agents, and appears to be higher or far higher for Omniscan," he said, estimating that roughly 3%-7% of patients with end-stage renal disease receiving high-dose Omniscan will develop NSF.

"In my opinion, the present data are sufficiently compelling to avoid Omniscan administration in patients with any significant level of renal disease," he added.

For gadolinium to be tolerated by humans, it must be chelated to a ligand molecule, he said. The likelihood of the ligand dissociating from the gadolinium ion (leaving the toxic free Gd+3) is far from equal among these five agents, being far greater in Omniscan and Optimark than in Magnevist, Multihance, or Prohance, judging from findings from in vitro and some in vivo studies. Because nonionic Omniscan and Optimark have a far lower conditional stability constant than do Magnevist, Multihance, and Prohance at normal body pH, it is possible that this may be related to the perceived greater incidence of NSF in patients who received Omniscan, Dr. Kanal said.

Elevated levels of calcium, phosphate, copper, iron, and zinc, which can compete with the gadolinium ion for coupling with the ligand molecule, may also exacerbate the risk of toxicity.

"You need a radiologist who knows what she or he is doing in this area to help design the study in a manner that will decrease dosing yet still be as diagnostic as possible. Trust your radiologist and then follow his feedback and guidance," he commented.

If a dialysis patient must have a contrast MRI, the American College of Radiology guidelines recommend that the patient be taken to hemodialysis immediately following the completion of the MR examination in which the gadolinium-based MR contrast agent had been administered. Radiologists should compile a database of all patients with stage III or more severe kidney disease who have had contrast-enhanced MRIs and follow them to ensure that they do not develop NSF, Dr. Kanal recommended.

"It used to be that patients with renal failure would specifically be sent to MR because the contrast agents were not directly nephrotoxic at the doses used, whereas giving iodine to patients with renal disease could cause iodine-induced nephropathy. Now we have something else to worry about for patients with renal disease: NSF," Dr. Kanal said.

Patients with stage IIIkidney disease or worse shouldn't be routinely given standard doses of gadolinium-based agents. DR. KANAL

The skin on the arm of a patient with contrast agent-induced nephrogenic systemic fibrosis shows scleroderma-like changes, including scarring (which is usually painful), tightening, thickening, and discoloration. Nephrogenic systemic fibrosis is fulminant in about 5% of cases and can prove to be fatal within weeks. Courtesy Dr. Shawn Cowper

CHICAGO — Imaging characteristics can help physicians distinguish the more aggressive pilomyxoid astrocytoma from a pilocytic astrocytoma and thereby guide treatment decisions, according to Dr. Luke Linscott, who presented his findings at the annual meeting of the American Society of Neuroradiology.

“If you see a patient with a presumed pilocytic astrocytoma [PCA] who is either very young or an adult, with a large, bulky tumor in an atypical location for PCA and, especially if that tumor demonstrates hemorrhage, the most likely diagnosis is aggressive pilomyxoid astrocytoma [PMA],” said Dr. Linscott of the University of Utah, Salt Lake City.

In what is the largest case series to date on PMA, Dr. Linscott and colleagues reviewed the images, pathology reports, and clinical information of 21 patients with pathology-confirmed PMA. The average age was 5 years, with a range from 9 months to 46 years, and there was a slight predominance of males. Researchers contributed cases from the United States, Canada, Norway, and South Africa.

The tumor's anatomic location is one diagnostic clue. Although PCAs are most commonly found in the posterior fossa and less commonly in the hypothalamus and optic chiasm, PMAs are more likely to be located in the hypothalamic/optic chiasm region, according to Dr. Linscott. However, in this series, more than 40% of PMAs were found in atypical locations such as the cerebral cortex (4 of 21), cerebellum (2 of 21), basal ganglia (2 of 21), and area around the fourth ventricle (1 of 21). “These atypical locations are more common than previously reported and are more common in older patients,” said Dr. Linscott.

Intratumoral hemorrhage is another important distinguishing feature. Although evidence of hemorrhage was noted in 20% of PMAs, it is extremely rare in PCAs, according to Dr. Linscott.

Rim enhancement on contrast-enhanced CT is also characteristic of PMA. In this series, 48% of cases showed heterogeneous rim enhancement, 43% showed uniform enhancement, and 9% showed no enhancement at all. Two cases showed cerebrospinal fluid dissemination.

Calcification is a characteristic finding of PCA. In this series, calcification was noted in only one case of PMA, making the diagnosis of PMA less likely, Dr. Linscott said.

Identifying a PMA has important clinical consequences. Because PMA is a clinically more aggressive tumor than PCA, distinguishing between these two tumor types may change the surgical and medical management of the patient, including more aggressive adjuvant chemotherapy and radiotherapy.

Cerebellar vermis tumor in 17-year-old boy on contrast-enhanced axial T1WI.

Axial T1WI shows nonenhancing posterior parietal tumor in a 2-year-old boy.

CT shows fluid-fluid levels in an acute intratumoral hemorrhage of a PMA.

T1 image with contrast shows teen's rim-enhancing lesion of the posterior fossa. Images courtesy Dr. Luke Linscott

CHICAGO — Imaging characteristics can help physicians distinguish the more aggressive pilomyxoid astrocytoma from a pilocytic astrocytoma and thereby guide treatment decisions, according to Dr. Luke Linscott, who presented his findings at the annual meeting of the American Society of Neuroradiology.

“If you see a patient with a presumed pilocytic astrocytoma [PCA] who is either very young or an adult, with a large, bulky tumor in an atypical location for PCA and, especially if that tumor demonstrates hemorrhage, the most likely diagnosis is aggressive pilomyxoid astrocytoma [PMA],” said Dr. Linscott of the University of Utah, Salt Lake City.

In what is the largest case series to date on PMA, Dr. Linscott and colleagues reviewed the images, pathology reports, and clinical information of 21 patients with pathology-confirmed PMA. The average age was 5 years, with a range from 9 months to 46 years, and there was a slight predominance of males. Researchers contributed cases from the United States, Canada, Norway, and South Africa.

The tumor's anatomic location is one diagnostic clue. Although PCAs are most commonly found in the posterior fossa and less commonly in the hypothalamus and optic chiasm, PMAs are more likely to be located in the hypothalamic/optic chiasm region, according to Dr. Linscott. However, in this series, more than 40% of PMAs were found in atypical locations such as the cerebral cortex (4 of 21), cerebellum (2 of 21), basal ganglia (2 of 21), and area around the fourth ventricle (1 of 21). “These atypical locations are more common than previously reported and are more common in older patients,” said Dr. Linscott.

Intratumoral hemorrhage is another important distinguishing feature. Although evidence of hemorrhage was noted in 20% of PMAs, it is extremely rare in PCAs, according to Dr. Linscott.

Rim enhancement on contrast-enhanced CT is also characteristic of PMA. In this series, 48% of cases showed heterogeneous rim enhancement, 43% showed uniform enhancement, and 9% showed no enhancement at all. Two cases showed cerebrospinal fluid dissemination.

Calcification is a characteristic finding of PCA. In this series, calcification was noted in only one case of PMA, making the diagnosis of PMA less likely, Dr. Linscott said.

Identifying a PMA has important clinical consequences. Because PMA is a clinically more aggressive tumor than PCA, distinguishing between these two tumor types may change the surgical and medical management of the patient, including more aggressive adjuvant chemotherapy and radiotherapy.

Cerebellar vermis tumor in 17-year-old boy on contrast-enhanced axial T1WI.

Axial T1WI shows nonenhancing posterior parietal tumor in a 2-year-old boy.

CT shows fluid-fluid levels in an acute intratumoral hemorrhage of a PMA.

T1 image with contrast shows teen's rim-enhancing lesion of the posterior fossa. Images courtesy Dr. Luke Linscott

CHICAGO — Imaging characteristics can help physicians distinguish the more aggressive pilomyxoid astrocytoma from a pilocytic astrocytoma and thereby guide treatment decisions, according to Dr. Luke Linscott, who presented his findings at the annual meeting of the American Society of Neuroradiology.

“If you see a patient with a presumed pilocytic astrocytoma [PCA] who is either very young or an adult, with a large, bulky tumor in an atypical location for PCA and, especially if that tumor demonstrates hemorrhage, the most likely diagnosis is aggressive pilomyxoid astrocytoma [PMA],” said Dr. Linscott of the University of Utah, Salt Lake City.

In what is the largest case series to date on PMA, Dr. Linscott and colleagues reviewed the images, pathology reports, and clinical information of 21 patients with pathology-confirmed PMA. The average age was 5 years, with a range from 9 months to 46 years, and there was a slight predominance of males. Researchers contributed cases from the United States, Canada, Norway, and South Africa.

The tumor's anatomic location is one diagnostic clue. Although PCAs are most commonly found in the posterior fossa and less commonly in the hypothalamus and optic chiasm, PMAs are more likely to be located in the hypothalamic/optic chiasm region, according to Dr. Linscott. However, in this series, more than 40% of PMAs were found in atypical locations such as the cerebral cortex (4 of 21), cerebellum (2 of 21), basal ganglia (2 of 21), and area around the fourth ventricle (1 of 21). “These atypical locations are more common than previously reported and are more common in older patients,” said Dr. Linscott.

Intratumoral hemorrhage is another important distinguishing feature. Although evidence of hemorrhage was noted in 20% of PMAs, it is extremely rare in PCAs, according to Dr. Linscott.

Rim enhancement on contrast-enhanced CT is also characteristic of PMA. In this series, 48% of cases showed heterogeneous rim enhancement, 43% showed uniform enhancement, and 9% showed no enhancement at all. Two cases showed cerebrospinal fluid dissemination.

Calcification is a characteristic finding of PCA. In this series, calcification was noted in only one case of PMA, making the diagnosis of PMA less likely, Dr. Linscott said.

Identifying a PMA has important clinical consequences. Because PMA is a clinically more aggressive tumor than PCA, distinguishing between these two tumor types may change the surgical and medical management of the patient, including more aggressive adjuvant chemotherapy and radiotherapy.

Cerebellar vermis tumor in 17-year-old boy on contrast-enhanced axial T1WI.

Axial T1WI shows nonenhancing posterior parietal tumor in a 2-year-old boy.

CT shows fluid-fluid levels in an acute intratumoral hemorrhage of a PMA.

T1 image with contrast shows teen's rim-enhancing lesion of the posterior fossa. Images courtesy Dr. Luke Linscott

BOSTON - People with obstructive sleep apnea syndrome showed poorer vigilance while driving than did normal controls, a result that could not be predicted by pretest measures of disease severity or subjective reports of sleepiness, according to a poster presented by Dr. Jon Tippin at the annual meeting of the American Academy of Neurology.

“[Obstructive sleep apnea syndrome] can now be added to the list of diseases, including dementing illnesses like Alzheimer's disease and Parkinson's disease, that cause vigilance problems [during driving],” said Dr. Tippin, a neurologist at the University of Iowa, Iowa City.

Vigilance was assessed using the Simulator for Interdisciplinary Research in Ergonomics and Neuroscience (SIREN), an interactive driving simulator adapted from a car fitted with projection screens in front of and behind the driver. Drivers were asked to respond by clicking the high-beam control as soon as they detected light targets flashed at unpredictable temporal intervals (average one per minute) at seven locations across the forward horizon. Hit rates (HR) and reaction times (RT) were the outcome measures. The hour-long test was administered in the late afternoon.

The overall hit rate was lower in drivers with obstructive sleep apnea syndrome (OSAS) (n = 25) than in normal controls (n = 41) (P = .018).

The data also suggested that peripheral targets were more likely to be missed by people with OSAS than were those located in the central field of vision (P = .0862). “These people do not have visual field impairments but rather they show inattention to things in the peripheral field. As [drivers] becomes more inattentive, they focus more on the things right in front of them,” said Dr. Tippin.

Although slower reaction times predicted poorer driving performance in all drivers (P is less than.03), there was no difference in mean reaction times between the groups.

People with OSAS were not sleepier than controls before the test, as indicated by the predrive Stanford Sleepiness Scale test. OSAS drivers were sleepier than controls at the end of the drive (P = .027), but only in OSAS drivers did the increased sleepiness correlate with poorer vigilance (as measured by lower hit rates, P = .0135). Objective tests of sleepiness, such as polysomnography and the Multiple Sleep Latency Test done on the evening of and day after the drive, respectively, also did not correlate with vigilance or driving performance.

“For patients with OSAS, the problem is less one of falling asleep than maintaining attention,” said Dr. Tippin.

Factors such as age, obesity, and a sedentary lifestyle raise the risk for OSAS.

For truck drivers, many of whom have several of these risk factors, the likelihood of OSAS may be elevated to four times that of the general population, said Dr. Tippin. Sleep deprivation and fragmentation may compound the problem in this population.

Stakeholders such as the Federal Motor Carrier Safety Administration (FMCSA), the trucking industry, and insurance carriers are working to develop guidelines regarding illness and driving.

Dr. Tippin suggested that OSA should be added to the list of conditions that compromise driving capability.

BOSTON - People with obstructive sleep apnea syndrome showed poorer vigilance while driving than did normal controls, a result that could not be predicted by pretest measures of disease severity or subjective reports of sleepiness, according to a poster presented by Dr. Jon Tippin at the annual meeting of the American Academy of Neurology.

“[Obstructive sleep apnea syndrome] can now be added to the list of diseases, including dementing illnesses like Alzheimer's disease and Parkinson's disease, that cause vigilance problems [during driving],” said Dr. Tippin, a neurologist at the University of Iowa, Iowa City.

Vigilance was assessed using the Simulator for Interdisciplinary Research in Ergonomics and Neuroscience (SIREN), an interactive driving simulator adapted from a car fitted with projection screens in front of and behind the driver. Drivers were asked to respond by clicking the high-beam control as soon as they detected light targets flashed at unpredictable temporal intervals (average one per minute) at seven locations across the forward horizon. Hit rates (HR) and reaction times (RT) were the outcome measures. The hour-long test was administered in the late afternoon.

The overall hit rate was lower in drivers with obstructive sleep apnea syndrome (OSAS) (n = 25) than in normal controls (n = 41) (P = .018).

The data also suggested that peripheral targets were more likely to be missed by people with OSAS than were those located in the central field of vision (P = .0862). “These people do not have visual field impairments but rather they show inattention to things in the peripheral field. As [drivers] becomes more inattentive, they focus more on the things right in front of them,” said Dr. Tippin.

Although slower reaction times predicted poorer driving performance in all drivers (P is less than.03), there was no difference in mean reaction times between the groups.

People with OSAS were not sleepier than controls before the test, as indicated by the predrive Stanford Sleepiness Scale test. OSAS drivers were sleepier than controls at the end of the drive (P = .027), but only in OSAS drivers did the increased sleepiness correlate with poorer vigilance (as measured by lower hit rates, P = .0135). Objective tests of sleepiness, such as polysomnography and the Multiple Sleep Latency Test done on the evening of and day after the drive, respectively, also did not correlate with vigilance or driving performance.

“For patients with OSAS, the problem is less one of falling asleep than maintaining attention,” said Dr. Tippin.

Factors such as age, obesity, and a sedentary lifestyle raise the risk for OSAS.

For truck drivers, many of whom have several of these risk factors, the likelihood of OSAS may be elevated to four times that of the general population, said Dr. Tippin. Sleep deprivation and fragmentation may compound the problem in this population.

Stakeholders such as the Federal Motor Carrier Safety Administration (FMCSA), the trucking industry, and insurance carriers are working to develop guidelines regarding illness and driving.

Dr. Tippin suggested that OSA should be added to the list of conditions that compromise driving capability.

BOSTON - People with obstructive sleep apnea syndrome showed poorer vigilance while driving than did normal controls, a result that could not be predicted by pretest measures of disease severity or subjective reports of sleepiness, according to a poster presented by Dr. Jon Tippin at the annual meeting of the American Academy of Neurology.

“[Obstructive sleep apnea syndrome] can now be added to the list of diseases, including dementing illnesses like Alzheimer's disease and Parkinson's disease, that cause vigilance problems [during driving],” said Dr. Tippin, a neurologist at the University of Iowa, Iowa City.

Vigilance was assessed using the Simulator for Interdisciplinary Research in Ergonomics and Neuroscience (SIREN), an interactive driving simulator adapted from a car fitted with projection screens in front of and behind the driver. Drivers were asked to respond by clicking the high-beam control as soon as they detected light targets flashed at unpredictable temporal intervals (average one per minute) at seven locations across the forward horizon. Hit rates (HR) and reaction times (RT) were the outcome measures. The hour-long test was administered in the late afternoon.

The overall hit rate was lower in drivers with obstructive sleep apnea syndrome (OSAS) (n = 25) than in normal controls (n = 41) (P = .018).

The data also suggested that peripheral targets were more likely to be missed by people with OSAS than were those located in the central field of vision (P = .0862). “These people do not have visual field impairments but rather they show inattention to things in the peripheral field. As [drivers] becomes more inattentive, they focus more on the things right in front of them,” said Dr. Tippin.

Although slower reaction times predicted poorer driving performance in all drivers (P is less than.03), there was no difference in mean reaction times between the groups.

People with OSAS were not sleepier than controls before the test, as indicated by the predrive Stanford Sleepiness Scale test. OSAS drivers were sleepier than controls at the end of the drive (P = .027), but only in OSAS drivers did the increased sleepiness correlate with poorer vigilance (as measured by lower hit rates, P = .0135). Objective tests of sleepiness, such as polysomnography and the Multiple Sleep Latency Test done on the evening of and day after the drive, respectively, also did not correlate with vigilance or driving performance.

“For patients with OSAS, the problem is less one of falling asleep than maintaining attention,” said Dr. Tippin.

Factors such as age, obesity, and a sedentary lifestyle raise the risk for OSAS.

For truck drivers, many of whom have several of these risk factors, the likelihood of OSAS may be elevated to four times that of the general population, said Dr. Tippin. Sleep deprivation and fragmentation may compound the problem in this population.

Stakeholders such as the Federal Motor Carrier Safety Administration (FMCSA), the trucking industry, and insurance carriers are working to develop guidelines regarding illness and driving.

Dr. Tippin suggested that OSA should be added to the list of conditions that compromise driving capability.

CHICAGO — Measurement of cerebral blood flow volume in a patient with glioma is a sensitive predictor of disease stability or progression, according to Dr. Meng Law, who presented his findings at the annual meeting of the American Society of Neuroradiology.

Using dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC-MRI), Dr. Law found that gliomas with a high relative cerebral blood volume (rCBV) showed significantly more rapid time to progression than did gliomas with a low rCBV. This information gained at the time of diagnosis can impact treatment decisions, including the extent of neurosurgical resection, or the choice of postoperative radiation or chemotherapy protocols.

This 10-year, retrospective study included 189 patients with histologically proved gliomas: low-grade astrocytomas (28), low-grade oligodendrogliomas (14), low-grade oligoastrocytomas (11), anaplastic astrocytomas (72), anaplastic oligoastrocytomas (12), and glioblastoma multiforme (52).

Patients underwent DSC-MRI, and measurements of rCBV were obtained by choosing the highest regional intratumoral rCBV after excluding large intratumoral vessels. Patients were followed up clinically and with MRI (median follow-up 3.2 years).

Dr. Law, currently of Mount Sinai Medical Center, New York, conducted this research while on the faculty of New York University.

Patients who progressed had a mean rCBV of 4.84 (n=130) and for patients who died the mean value was 3.82 (n=36), values that were much higher than in those who showed a complete response (1.41, n=4) or who had stable disease (2.36, n=41). P values from logistic regression demonstrated that age and rCBV were significant predictors of disease progression and death.

Patients with higher rCBV scores showed more rapid time to progression (TTP), as seen in the image, below. Those patients with an rCBV greater than 1.75 had a mean TTP of 265 days, compared with 3,585 days for those with an rCBV less than 1.75.

These values were derived from Kaplan-Meier Progression Free Survival curves. The 1.75 threshold for rCBV has a sensitivity of about 90% for distinguishing low-grade from high-grade tumors, said Dr. Law.

DSC-MRI is a technique that can provide physiologic information about vascular endothelial proliferation, vascular density, and angiogenesis. Since vascular proliferation is an important factor in the biology of gliomas, Dr. Law said, it is not surprising that DSC-MRI can provide an accurate means of characterizing tumor biology.

According to Dr. Law, while histopathology is the standard reference for determining glioma tumor biology and making prognostic decisions, histopathology has significant limitations. These include sampling errors, inter- and intraobserver variability, and dynamic changes as the tumor progresses.

Since patients with misclassified gliomas may not receive optimum treatment, Dr. Law suggested that measuring cerebral blood volume may be as sensitive, or even more sensitive, a predictor than pathology when assessing glioma outcomes.

He is investigating this further in a multicenter study using perfusion in predicting patient outcome; the study is being funded by the nonprofit Accelerate Brain Cancer Cure in Washington.

Imaging shows disease progression over a 6-month period in a man with a pathology-proven low-grade astrocytoma but a high baseline relative cerebral blood volume (rCBV). Dr. Law said that while histopathology is the standard reference for determining glioma biology and making prognostic decisions, it has limitations. Images courtesy Dr. Meng Law

CHICAGO — Measurement of cerebral blood flow volume in a patient with glioma is a sensitive predictor of disease stability or progression, according to Dr. Meng Law, who presented his findings at the annual meeting of the American Society of Neuroradiology.

Using dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC-MRI), Dr. Law found that gliomas with a high relative cerebral blood volume (rCBV) showed significantly more rapid time to progression than did gliomas with a low rCBV. This information gained at the time of diagnosis can impact treatment decisions, including the extent of neurosurgical resection, or the choice of postoperative radiation or chemotherapy protocols.

This 10-year, retrospective study included 189 patients with histologically proved gliomas: low-grade astrocytomas (28), low-grade oligodendrogliomas (14), low-grade oligoastrocytomas (11), anaplastic astrocytomas (72), anaplastic oligoastrocytomas (12), and glioblastoma multiforme (52).

Patients underwent DSC-MRI, and measurements of rCBV were obtained by choosing the highest regional intratumoral rCBV after excluding large intratumoral vessels. Patients were followed up clinically and with MRI (median follow-up 3.2 years).

Dr. Law, currently of Mount Sinai Medical Center, New York, conducted this research while on the faculty of New York University.

Patients who progressed had a mean rCBV of 4.84 (n=130) and for patients who died the mean value was 3.82 (n=36), values that were much higher than in those who showed a complete response (1.41, n=4) or who had stable disease (2.36, n=41). P values from logistic regression demonstrated that age and rCBV were significant predictors of disease progression and death.

Patients with higher rCBV scores showed more rapid time to progression (TTP), as seen in the image, below. Those patients with an rCBV greater than 1.75 had a mean TTP of 265 days, compared with 3,585 days for those with an rCBV less than 1.75.

These values were derived from Kaplan-Meier Progression Free Survival curves. The 1.75 threshold for rCBV has a sensitivity of about 90% for distinguishing low-grade from high-grade tumors, said Dr. Law.

DSC-MRI is a technique that can provide physiologic information about vascular endothelial proliferation, vascular density, and angiogenesis. Since vascular proliferation is an important factor in the biology of gliomas, Dr. Law said, it is not surprising that DSC-MRI can provide an accurate means of characterizing tumor biology.

According to Dr. Law, while histopathology is the standard reference for determining glioma tumor biology and making prognostic decisions, histopathology has significant limitations. These include sampling errors, inter- and intraobserver variability, and dynamic changes as the tumor progresses.

Since patients with misclassified gliomas may not receive optimum treatment, Dr. Law suggested that measuring cerebral blood volume may be as sensitive, or even more sensitive, a predictor than pathology when assessing glioma outcomes.

He is investigating this further in a multicenter study using perfusion in predicting patient outcome; the study is being funded by the nonprofit Accelerate Brain Cancer Cure in Washington.

Imaging shows disease progression over a 6-month period in a man with a pathology-proven low-grade astrocytoma but a high baseline relative cerebral blood volume (rCBV). Dr. Law said that while histopathology is the standard reference for determining glioma biology and making prognostic decisions, it has limitations. Images courtesy Dr. Meng Law

CHICAGO — Measurement of cerebral blood flow volume in a patient with glioma is a sensitive predictor of disease stability or progression, according to Dr. Meng Law, who presented his findings at the annual meeting of the American Society of Neuroradiology.

Using dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC-MRI), Dr. Law found that gliomas with a high relative cerebral blood volume (rCBV) showed significantly more rapid time to progression than did gliomas with a low rCBV. This information gained at the time of diagnosis can impact treatment decisions, including the extent of neurosurgical resection, or the choice of postoperative radiation or chemotherapy protocols.

This 10-year, retrospective study included 189 patients with histologically proved gliomas: low-grade astrocytomas (28), low-grade oligodendrogliomas (14), low-grade oligoastrocytomas (11), anaplastic astrocytomas (72), anaplastic oligoastrocytomas (12), and glioblastoma multiforme (52).

Patients underwent DSC-MRI, and measurements of rCBV were obtained by choosing the highest regional intratumoral rCBV after excluding large intratumoral vessels. Patients were followed up clinically and with MRI (median follow-up 3.2 years).

Dr. Law, currently of Mount Sinai Medical Center, New York, conducted this research while on the faculty of New York University.

Patients who progressed had a mean rCBV of 4.84 (n=130) and for patients who died the mean value was 3.82 (n=36), values that were much higher than in those who showed a complete response (1.41, n=4) or who had stable disease (2.36, n=41). P values from logistic regression demonstrated that age and rCBV were significant predictors of disease progression and death.

Patients with higher rCBV scores showed more rapid time to progression (TTP), as seen in the image, below. Those patients with an rCBV greater than 1.75 had a mean TTP of 265 days, compared with 3,585 days for those with an rCBV less than 1.75.

These values were derived from Kaplan-Meier Progression Free Survival curves. The 1.75 threshold for rCBV has a sensitivity of about 90% for distinguishing low-grade from high-grade tumors, said Dr. Law.

DSC-MRI is a technique that can provide physiologic information about vascular endothelial proliferation, vascular density, and angiogenesis. Since vascular proliferation is an important factor in the biology of gliomas, Dr. Law said, it is not surprising that DSC-MRI can provide an accurate means of characterizing tumor biology.

According to Dr. Law, while histopathology is the standard reference for determining glioma tumor biology and making prognostic decisions, histopathology has significant limitations. These include sampling errors, inter- and intraobserver variability, and dynamic changes as the tumor progresses.

Since patients with misclassified gliomas may not receive optimum treatment, Dr. Law suggested that measuring cerebral blood volume may be as sensitive, or even more sensitive, a predictor than pathology when assessing glioma outcomes.

He is investigating this further in a multicenter study using perfusion in predicting patient outcome; the study is being funded by the nonprofit Accelerate Brain Cancer Cure in Washington.

Imaging shows disease progression over a 6-month period in a man with a pathology-proven low-grade astrocytoma but a high baseline relative cerebral blood volume (rCBV). Dr. Law said that while histopathology is the standard reference for determining glioma biology and making prognostic decisions, it has limitations. Images courtesy Dr. Meng Law

BOSTON – Judicious use of antidepressants can ameliorate the psychiatric stressors that exacerbate moderate to severe irritable bowel syndrome symptoms, Dr. Douglas A. Drossman said at a meeting on neurogastroenterology and motility.

These agents can also act directly in the gut to control bowel dysfunction, said Dr. Drossman, codirector of the University of North Carolina Center for Functional GI and Motility Disorders, in Chapel Hill. “The more severe the IBS, the more likely the patient is to have comorbid psychosocial factors,” Dr. Drossman said. “Any treatment that might reduce the stressor itself or the interpretation of the stressor through psychological pathways or through antidepressants is likely to have some benefit.”

One of the first hurdles is to confront maladaptive negative beliefs a patient may have that can undermine good outcomes. Patients who feel that they have no control over their symptoms, who “catastrophize” and believe their condition will never get better, or who have a history of abuse have poorer outcomes–regardless of their treatment or condition, Dr. Drossman said.

He urges clinicians to establish a productive physician/patient relationship at the outset by identifying patient worries, providing reassurance, explaining the physiologic basis of symptoms, setting realistic treatment goals and time frames, and addressing cost concerns.

When choosing an antidepressant for irritable bowel syndrome (IBS), clinicians must consider the medication class and features of a particular medication within the class. Tricyclic antidepressants (TCAs) with noradrenergic activity are useful for IBS with diarrhea, especially for those patients with comorbid pain and depression. Dr. Drossman does not favor TCAs such as amitriptyline, which may cause side effects that limit tolerability through anticholinergic and antihistaminergic effects. Instead, he recommends desipramine or nortriptyline.

Selective serotonin reuptake inhibitors (SSRIs) are a good choice for patients with IBS with constipation who may also have depression, panic or anxiety symptoms, or obsessive-compulsive disorders. This makes SSRIs appropriate for housebound patients who fear having an IBS episode while away from home. Dr. Drossman tends to stay away from short-acting agents such as paroxetine (Paxil), in order to minimize discontinuation side effects. He prefers medium-acting citalopram (Celexa) or escitalopram (Lexapro), or long-acting fluoxetine. SSRIs tend to have negligible effects on noradrenergic receptors and thus do not provide pain relief and may cause agitation because of serotonergic bursts when treatment is initiated, Dr. Drossman said.

Duloxetine (Cymbalta), a serotonin norepinephrine reuptake inhibitor (SNRI), has potent effects on noradrenergic and serotonergic receptors and minor effects on histaminergic and cholinergic systems. Because duloxetine is indicated for treating depression and managing neuropathic pain associated with diabetic peripheral neuropathy, it may be of particular benefit for a depressed IBS patient with prominent pain symptoms.

Sometimes, antipsychotics have a place in IBS management, Dr. Drossman said. “We are seeing an increasing use of antipsychotics in the primary care sector for conditions like anxiety and personality disorders–agents that [primary care physicians] would never have thought about touching years ago,” he said.

Dr. Drossman uses quetiapine (Seroquel) for sedation to treat extreme anxiety and comorbid bipolar and personality disorders, and as augmentation with antidepressants, giving a 50–200-mg dose before bedtime–well below the typical antipsychotic dose of 400 mg. However, he cautions that physicians should consider psychiatric consultation before making this treatment decision.

Dr. Drossman begins pharmacotherapy after symptomatic medical treatment and stress reduction techniques such as exercise and yoga fail. He starts with a low dose of a TCA, SSRI, or SNRI for 4–6 weeks, reevaluates the patient, increases the dose if necessary, and continues treatment for an additional 4–6 weeks. If symptoms are not controlled adequately, he may augment therapy by adding a drug from another class, such as buspirone, which has bowel-relaxing effects, or refer to a psychiatrist.

BOSTON – Judicious use of antidepressants can ameliorate the psychiatric stressors that exacerbate moderate to severe irritable bowel syndrome symptoms, Dr. Douglas A. Drossman said at a meeting on neurogastroenterology and motility.

These agents can also act directly in the gut to control bowel dysfunction, said Dr. Drossman, codirector of the University of North Carolina Center for Functional GI and Motility Disorders, in Chapel Hill. “The more severe the IBS, the more likely the patient is to have comorbid psychosocial factors,” Dr. Drossman said. “Any treatment that might reduce the stressor itself or the interpretation of the stressor through psychological pathways or through antidepressants is likely to have some benefit.”

One of the first hurdles is to confront maladaptive negative beliefs a patient may have that can undermine good outcomes. Patients who feel that they have no control over their symptoms, who “catastrophize” and believe their condition will never get better, or who have a history of abuse have poorer outcomes–regardless of their treatment or condition, Dr. Drossman said.

He urges clinicians to establish a productive physician/patient relationship at the outset by identifying patient worries, providing reassurance, explaining the physiologic basis of symptoms, setting realistic treatment goals and time frames, and addressing cost concerns.

When choosing an antidepressant for irritable bowel syndrome (IBS), clinicians must consider the medication class and features of a particular medication within the class. Tricyclic antidepressants (TCAs) with noradrenergic activity are useful for IBS with diarrhea, especially for those patients with comorbid pain and depression. Dr. Drossman does not favor TCAs such as amitriptyline, which may cause side effects that limit tolerability through anticholinergic and antihistaminergic effects. Instead, he recommends desipramine or nortriptyline.

Selective serotonin reuptake inhibitors (SSRIs) are a good choice for patients with IBS with constipation who may also have depression, panic or anxiety symptoms, or obsessive-compulsive disorders. This makes SSRIs appropriate for housebound patients who fear having an IBS episode while away from home. Dr. Drossman tends to stay away from short-acting agents such as paroxetine (Paxil), in order to minimize discontinuation side effects. He prefers medium-acting citalopram (Celexa) or escitalopram (Lexapro), or long-acting fluoxetine. SSRIs tend to have negligible effects on noradrenergic receptors and thus do not provide pain relief and may cause agitation because of serotonergic bursts when treatment is initiated, Dr. Drossman said.

Duloxetine (Cymbalta), a serotonin norepinephrine reuptake inhibitor (SNRI), has potent effects on noradrenergic and serotonergic receptors and minor effects on histaminergic and cholinergic systems. Because duloxetine is indicated for treating depression and managing neuropathic pain associated with diabetic peripheral neuropathy, it may be of particular benefit for a depressed IBS patient with prominent pain symptoms.

Sometimes, antipsychotics have a place in IBS management, Dr. Drossman said. “We are seeing an increasing use of antipsychotics in the primary care sector for conditions like anxiety and personality disorders–agents that [primary care physicians] would never have thought about touching years ago,” he said.

Dr. Drossman uses quetiapine (Seroquel) for sedation to treat extreme anxiety and comorbid bipolar and personality disorders, and as augmentation with antidepressants, giving a 50–200-mg dose before bedtime–well below the typical antipsychotic dose of 400 mg. However, he cautions that physicians should consider psychiatric consultation before making this treatment decision.

Dr. Drossman begins pharmacotherapy after symptomatic medical treatment and stress reduction techniques such as exercise and yoga fail. He starts with a low dose of a TCA, SSRI, or SNRI for 4–6 weeks, reevaluates the patient, increases the dose if necessary, and continues treatment for an additional 4–6 weeks. If symptoms are not controlled adequately, he may augment therapy by adding a drug from another class, such as buspirone, which has bowel-relaxing effects, or refer to a psychiatrist.

BOSTON – Judicious use of antidepressants can ameliorate the psychiatric stressors that exacerbate moderate to severe irritable bowel syndrome symptoms, Dr. Douglas A. Drossman said at a meeting on neurogastroenterology and motility.

These agents can also act directly in the gut to control bowel dysfunction, said Dr. Drossman, codirector of the University of North Carolina Center for Functional GI and Motility Disorders, in Chapel Hill. “The more severe the IBS, the more likely the patient is to have comorbid psychosocial factors,” Dr. Drossman said. “Any treatment that might reduce the stressor itself or the interpretation of the stressor through psychological pathways or through antidepressants is likely to have some benefit.”

One of the first hurdles is to confront maladaptive negative beliefs a patient may have that can undermine good outcomes. Patients who feel that they have no control over their symptoms, who “catastrophize” and believe their condition will never get better, or who have a history of abuse have poorer outcomes–regardless of their treatment or condition, Dr. Drossman said.

He urges clinicians to establish a productive physician/patient relationship at the outset by identifying patient worries, providing reassurance, explaining the physiologic basis of symptoms, setting realistic treatment goals and time frames, and addressing cost concerns.

When choosing an antidepressant for irritable bowel syndrome (IBS), clinicians must consider the medication class and features of a particular medication within the class. Tricyclic antidepressants (TCAs) with noradrenergic activity are useful for IBS with diarrhea, especially for those patients with comorbid pain and depression. Dr. Drossman does not favor TCAs such as amitriptyline, which may cause side effects that limit tolerability through anticholinergic and antihistaminergic effects. Instead, he recommends desipramine or nortriptyline.

Selective serotonin reuptake inhibitors (SSRIs) are a good choice for patients with IBS with constipation who may also have depression, panic or anxiety symptoms, or obsessive-compulsive disorders. This makes SSRIs appropriate for housebound patients who fear having an IBS episode while away from home. Dr. Drossman tends to stay away from short-acting agents such as paroxetine (Paxil), in order to minimize discontinuation side effects. He prefers medium-acting citalopram (Celexa) or escitalopram (Lexapro), or long-acting fluoxetine. SSRIs tend to have negligible effects on noradrenergic receptors and thus do not provide pain relief and may cause agitation because of serotonergic bursts when treatment is initiated, Dr. Drossman said.

Duloxetine (Cymbalta), a serotonin norepinephrine reuptake inhibitor (SNRI), has potent effects on noradrenergic and serotonergic receptors and minor effects on histaminergic and cholinergic systems. Because duloxetine is indicated for treating depression and managing neuropathic pain associated with diabetic peripheral neuropathy, it may be of particular benefit for a depressed IBS patient with prominent pain symptoms.

Sometimes, antipsychotics have a place in IBS management, Dr. Drossman said. “We are seeing an increasing use of antipsychotics in the primary care sector for conditions like anxiety and personality disorders–agents that [primary care physicians] would never have thought about touching years ago,” he said.

Dr. Drossman uses quetiapine (Seroquel) for sedation to treat extreme anxiety and comorbid bipolar and personality disorders, and as augmentation with antidepressants, giving a 50–200-mg dose before bedtime–well below the typical antipsychotic dose of 400 mg. However, he cautions that physicians should consider psychiatric consultation before making this treatment decision.

Dr. Drossman begins pharmacotherapy after symptomatic medical treatment and stress reduction techniques such as exercise and yoga fail. He starts with a low dose of a TCA, SSRI, or SNRI for 4–6 weeks, reevaluates the patient, increases the dose if necessary, and continues treatment for an additional 4–6 weeks. If symptoms are not controlled adequately, he may augment therapy by adding a drug from another class, such as buspirone, which has bowel-relaxing effects, or refer to a psychiatrist.

CHICAGO – With the use of a new method that provides objective and specific measurement of iron deposition in brain tissue in vivo, investigators have been able to quantify the increased iron accumulation in the deep gray matter of patients with multiple sclerosis.

The iron accumulation was positively correlated with both lesion load and neuropsychological test performance, according to Dr. Yulin Ge, who presented his findings at the annual meeting of the American Society of Neuroradiology.

The reason why iron has accumulated in these regions “is probably because the axons are transected by the MS lesions, interrupting iron outflow from iron-rich deep gray matter nuclei to projected cortical sites,” he said.

Dr. Ge's work was awarded the 2007 ASNR Cornelius G. Dyke Memorial Award for excellence in original, unpublished research in neuroradiology.

Using magnetic field correlation (MFC) imaging, Dr. Ge and his colleagues studied 17 patients with relapsing-remitting multiple sclerosis (MS) and 14 age-matched normal controls with a 3-T MR system. MFC imaging is a recently developed MR method that applies a unique iron contrast mechanism for measuring the iron deposition in vivo.

There was significantly more iron deposition in the deep gray matter of patients with MS than that in normal controls (P less than .03), with an average increase of 24% in the globus pallidus, 39.5% in the putamen, and 30.6% in the thalamus. Low iron concentrations in patients relative to controls were noted in the frontal white matter and the genu and splenium of the corpus callosum.

Increased iron deposition measured with MFC in the deep gray matter of MS patients was positively correlated with total number of brain lesions (thalamus: P = .01; globus pallidus: P = .02).

Increased iron in deep gray matter was correlated inversely and significantly with performance on several neuropsychological tests, including the Rey Complex Figure Test, the California Verbal Learning Test, and the Digit Span Backward test, Dr. Ge reported. “This is very exciting,” says Dr. Ge, a radiologist at New York University, New York. “Researchers used to feel MS is a white matter disease. Now we know there are deep gray matter neurodegenerative abnormalities, which we think are mainly due to excessive iron accumulation in these regions.”

Abnormal iron deposition is a causal factor of neurodegenerative pathology in MS, said Dr. Ge, who noted that his MFC findings support observations made using diffusion tensor imaging and MR spectroscopy demonstrating gray matter involvement in MS. In addition to providing mechanistic clues of MS pathophysiology, MFC will be a sensitive tool to evaluate MS patients and to monitor the effects of iron chelating agents and other neuroprotective MS treatments, he said.

T2-weighted images (left) and MFC color maps (right) in a 29-year-old MS patient (top) and a 32-year-old control (bottom). High iron levels are seen in deep gray matter regions (arrows) in MS. Courtesy Dr. Yulin Ge

CHICAGO – With the use of a new method that provides objective and specific measurement of iron deposition in brain tissue in vivo, investigators have been able to quantify the increased iron accumulation in the deep gray matter of patients with multiple sclerosis.

The iron accumulation was positively correlated with both lesion load and neuropsychological test performance, according to Dr. Yulin Ge, who presented his findings at the annual meeting of the American Society of Neuroradiology.

The reason why iron has accumulated in these regions “is probably because the axons are transected by the MS lesions, interrupting iron outflow from iron-rich deep gray matter nuclei to projected cortical sites,” he said.

Dr. Ge's work was awarded the 2007 ASNR Cornelius G. Dyke Memorial Award for excellence in original, unpublished research in neuroradiology.

Using magnetic field correlation (MFC) imaging, Dr. Ge and his colleagues studied 17 patients with relapsing-remitting multiple sclerosis (MS) and 14 age-matched normal controls with a 3-T MR system. MFC imaging is a recently developed MR method that applies a unique iron contrast mechanism for measuring the iron deposition in vivo.

There was significantly more iron deposition in the deep gray matter of patients with MS than that in normal controls (P less than .03), with an average increase of 24% in the globus pallidus, 39.5% in the putamen, and 30.6% in the thalamus. Low iron concentrations in patients relative to controls were noted in the frontal white matter and the genu and splenium of the corpus callosum.

Increased iron deposition measured with MFC in the deep gray matter of MS patients was positively correlated with total number of brain lesions (thalamus: P = .01; globus pallidus: P = .02).

Increased iron in deep gray matter was correlated inversely and significantly with performance on several neuropsychological tests, including the Rey Complex Figure Test, the California Verbal Learning Test, and the Digit Span Backward test, Dr. Ge reported. “This is very exciting,” says Dr. Ge, a radiologist at New York University, New York. “Researchers used to feel MS is a white matter disease. Now we know there are deep gray matter neurodegenerative abnormalities, which we think are mainly due to excessive iron accumulation in these regions.”

Abnormal iron deposition is a causal factor of neurodegenerative pathology in MS, said Dr. Ge, who noted that his MFC findings support observations made using diffusion tensor imaging and MR spectroscopy demonstrating gray matter involvement in MS. In addition to providing mechanistic clues of MS pathophysiology, MFC will be a sensitive tool to evaluate MS patients and to monitor the effects of iron chelating agents and other neuroprotective MS treatments, he said.

T2-weighted images (left) and MFC color maps (right) in a 29-year-old MS patient (top) and a 32-year-old control (bottom). High iron levels are seen in deep gray matter regions (arrows) in MS. Courtesy Dr. Yulin Ge

CHICAGO – With the use of a new method that provides objective and specific measurement of iron deposition in brain tissue in vivo, investigators have been able to quantify the increased iron accumulation in the deep gray matter of patients with multiple sclerosis.

The iron accumulation was positively correlated with both lesion load and neuropsychological test performance, according to Dr. Yulin Ge, who presented his findings at the annual meeting of the American Society of Neuroradiology.

The reason why iron has accumulated in these regions “is probably because the axons are transected by the MS lesions, interrupting iron outflow from iron-rich deep gray matter nuclei to projected cortical sites,” he said.

Dr. Ge's work was awarded the 2007 ASNR Cornelius G. Dyke Memorial Award for excellence in original, unpublished research in neuroradiology.

Using magnetic field correlation (MFC) imaging, Dr. Ge and his colleagues studied 17 patients with relapsing-remitting multiple sclerosis (MS) and 14 age-matched normal controls with a 3-T MR system. MFC imaging is a recently developed MR method that applies a unique iron contrast mechanism for measuring the iron deposition in vivo.

There was significantly more iron deposition in the deep gray matter of patients with MS than that in normal controls (P less than .03), with an average increase of 24% in the globus pallidus, 39.5% in the putamen, and 30.6% in the thalamus. Low iron concentrations in patients relative to controls were noted in the frontal white matter and the genu and splenium of the corpus callosum.

Increased iron deposition measured with MFC in the deep gray matter of MS patients was positively correlated with total number of brain lesions (thalamus: P = .01; globus pallidus: P = .02).

Increased iron in deep gray matter was correlated inversely and significantly with performance on several neuropsychological tests, including the Rey Complex Figure Test, the California Verbal Learning Test, and the Digit Span Backward test, Dr. Ge reported. “This is very exciting,” says Dr. Ge, a radiologist at New York University, New York. “Researchers used to feel MS is a white matter disease. Now we know there are deep gray matter neurodegenerative abnormalities, which we think are mainly due to excessive iron accumulation in these regions.”

Abnormal iron deposition is a causal factor of neurodegenerative pathology in MS, said Dr. Ge, who noted that his MFC findings support observations made using diffusion tensor imaging and MR spectroscopy demonstrating gray matter involvement in MS. In addition to providing mechanistic clues of MS pathophysiology, MFC will be a sensitive tool to evaluate MS patients and to monitor the effects of iron chelating agents and other neuroprotective MS treatments, he said.

T2-weighted images (left) and MFC color maps (right) in a 29-year-old MS patient (top) and a 32-year-old control (bottom). High iron levels are seen in deep gray matter regions (arrows) in MS. Courtesy Dr. Yulin Ge

BOSTON – The addition of safinamide to ongoing dopamine agonist monotherapy lessened motor and cognitive symptoms in a group of patients with Parkinson's disease, according to the results of a randomized, placebo-controlled, multinational Phase III trial.

The higher dose tested offered no advantage over the lower dose, according to the presentation made by Dr. Fabrizio Stocchi at the 59th annual meeting of the American Academy of Neurology.

“Dopamine agonists tend to lose their effects [with extended use],” says Dr. Stocchi, a professor of neurology at the Institute of Neurology IRCCS San Raffaele Pisana in Rome. “We asked whether another compound can expand dopamine agonist monotherapy.”

Safinamide is a selective and reversible inhibitor of MAO-B. It inhibits dopamine reuptake and glutamate release, and does not potentiate the effects of tyramine.

A total of 270 patients with early Parkinson's disease (PD) maintained for at least 4 weeks on dopamine agonist monotherapy were randomized into three groups receiving either supplemental safinamide in low dose (50–100 mg/day), high dose (150–200 mg/day), or placebo.

The results showed that after 24 weeks of treatment with low-dose safinamide plus dopamine agonist, the Unified Parkinson's Disease Rating Scale (UPDRS) Part III motor score was significantly improved over the effect of dopamine monotherapy (mean change from baseline: low dose vs. control: −6.0 plus or minus 7.2 vs. −3.6 plus or minus 7.1; P=.0125).

Scores for the high-dose safinamide group (−3.9 plus or minus 6.0) were not significantly better than those of the controls. The number of responders (patients showing a 30% improvement or more) on the UPDRS III also increased with the low-dose combination therapy.

Safinamide/dopamine agonist combination therapy had other benefits.

Significant improvements with low-dose safinamide were also noted on the UPDRS Part II Activities of Daily Living Score, the EuroQoL, and the Clinical Global Impression-C. No clinically significant side effects were reported with either dose of safinamide.

Low-dose safinamide-treated patients also performed better on the Cogtest battery, designed to evaluate cognitive domains known to be impaired in Parkinson's patients.

Improved scores were noted in several cognitive domains, including spatial working memory, strategic target detection, and auditory number sequencing.

Dr. Stocchi is involved in a 1-year extension phase of the study. A Phase III pivotal study of safinamide as an add-on to levodopa in patients with mid- to late-stage Parkinson's is underway.

BOSTON – The addition of safinamide to ongoing dopamine agonist monotherapy lessened motor and cognitive symptoms in a group of patients with Parkinson's disease, according to the results of a randomized, placebo-controlled, multinational Phase III trial.

The higher dose tested offered no advantage over the lower dose, according to the presentation made by Dr. Fabrizio Stocchi at the 59th annual meeting of the American Academy of Neurology.

“Dopamine agonists tend to lose their effects [with extended use],” says Dr. Stocchi, a professor of neurology at the Institute of Neurology IRCCS San Raffaele Pisana in Rome. “We asked whether another compound can expand dopamine agonist monotherapy.”

Safinamide is a selective and reversible inhibitor of MAO-B. It inhibits dopamine reuptake and glutamate release, and does not potentiate the effects of tyramine.

A total of 270 patients with early Parkinson's disease (PD) maintained for at least 4 weeks on dopamine agonist monotherapy were randomized into three groups receiving either supplemental safinamide in low dose (50–100 mg/day), high dose (150–200 mg/day), or placebo.

The results showed that after 24 weeks of treatment with low-dose safinamide plus dopamine agonist, the Unified Parkinson's Disease Rating Scale (UPDRS) Part III motor score was significantly improved over the effect of dopamine monotherapy (mean change from baseline: low dose vs. control: −6.0 plus or minus 7.2 vs. −3.6 plus or minus 7.1; P=.0125).

Scores for the high-dose safinamide group (−3.9 plus or minus 6.0) were not significantly better than those of the controls. The number of responders (patients showing a 30% improvement or more) on the UPDRS III also increased with the low-dose combination therapy.

Safinamide/dopamine agonist combination therapy had other benefits.

Significant improvements with low-dose safinamide were also noted on the UPDRS Part II Activities of Daily Living Score, the EuroQoL, and the Clinical Global Impression-C. No clinically significant side effects were reported with either dose of safinamide.

Low-dose safinamide-treated patients also performed better on the Cogtest battery, designed to evaluate cognitive domains known to be impaired in Parkinson's patients.

Improved scores were noted in several cognitive domains, including spatial working memory, strategic target detection, and auditory number sequencing.

Dr. Stocchi is involved in a 1-year extension phase of the study. A Phase III pivotal study of safinamide as an add-on to levodopa in patients with mid- to late-stage Parkinson's is underway.

BOSTON – The addition of safinamide to ongoing dopamine agonist monotherapy lessened motor and cognitive symptoms in a group of patients with Parkinson's disease, according to the results of a randomized, placebo-controlled, multinational Phase III trial.

The higher dose tested offered no advantage over the lower dose, according to the presentation made by Dr. Fabrizio Stocchi at the 59th annual meeting of the American Academy of Neurology.

“Dopamine agonists tend to lose their effects [with extended use],” says Dr. Stocchi, a professor of neurology at the Institute of Neurology IRCCS San Raffaele Pisana in Rome. “We asked whether another compound can expand dopamine agonist monotherapy.”

Safinamide is a selective and reversible inhibitor of MAO-B. It inhibits dopamine reuptake and glutamate release, and does not potentiate the effects of tyramine.

A total of 270 patients with early Parkinson's disease (PD) maintained for at least 4 weeks on dopamine agonist monotherapy were randomized into three groups receiving either supplemental safinamide in low dose (50–100 mg/day), high dose (150–200 mg/day), or placebo.

The results showed that after 24 weeks of treatment with low-dose safinamide plus dopamine agonist, the Unified Parkinson's Disease Rating Scale (UPDRS) Part III motor score was significantly improved over the effect of dopamine monotherapy (mean change from baseline: low dose vs. control: −6.0 plus or minus 7.2 vs. −3.6 plus or minus 7.1; P=.0125).

Scores for the high-dose safinamide group (−3.9 plus or minus 6.0) were not significantly better than those of the controls. The number of responders (patients showing a 30% improvement or more) on the UPDRS III also increased with the low-dose combination therapy.

Safinamide/dopamine agonist combination therapy had other benefits.

Significant improvements with low-dose safinamide were also noted on the UPDRS Part II Activities of Daily Living Score, the EuroQoL, and the Clinical Global Impression-C. No clinically significant side effects were reported with either dose of safinamide.

Low-dose safinamide-treated patients also performed better on the Cogtest battery, designed to evaluate cognitive domains known to be impaired in Parkinson's patients.

Improved scores were noted in several cognitive domains, including spatial working memory, strategic target detection, and auditory number sequencing.

Dr. Stocchi is involved in a 1-year extension phase of the study. A Phase III pivotal study of safinamide as an add-on to levodopa in patients with mid- to late-stage Parkinson's is underway.

BOSTON – Depression, anxiety, and sleep problems rather than disease explain why some patients with Parkinson's disease call their physicians more frequently than others, according to results of a study presented by Dr. Melissa J. Nirenberg in a poster presentation at the annual meeting of the American Academy of Neurology.

Treating these “invisible” symptoms may both help the patients' quality of life and decrease their health care use, she reported.

In the study, frequent callers–who made an average of 2.4 calls in 100 days–had significantly higher anxiety scores on the Beck Anxiety Inventory and higher depression scores on the Beck Depression Inventory than did those who called infrequently–or a mean of 0.6 calls in 100 days. They also had lower quality of life scores on the Parkinson's Disease Quality of Life scale, reported Dr. Nirenberg. Sleep problems were a universal complaint among frequent callers, but these issues were reported by only 36% of the infrequent callers, a significant difference.

While patients in both groups had moderate motor disability, no differences between groups were found as measured by the motor Unified Parkinson's Disease Rating Scale, Hoehn and Yahr scale, or Schwab and England Disability scale.

The study comprised 44 nondemented Parkinson's disease outpatients who were treated over 4 months in a movement disorders clinic. They all underwent neuropsychiatric and disability testing. Patients who called more than the mean rate of 1.9 calls in 100 days were assigned to the frequent callers group, and those who called less than the mean rate were assigned to the infrequent callers group. Calling history was determined by retrospective chart review.

“These [frequent callers] look good but feel bad,” says Dr. Nirenberg, who is the associate director of the Parkinson's Disease and Movement Disorders Institute at Cornell University, New York. She believes that because anxiety, depression, and sleep disorders are not readily apparent, it might make sense to focus instead on treating the motor symptoms. Even physicians who recognize the importance of the nonmotor symptoms of Parkinson's disease may not have time to ask about them during a routine office visit, and as a result, may be undertreating these symptoms.

Increased telephone health care use has a significant impact on physicians, said Dr. Nirenberg. These calls take up a tremendous amount of the time. While not assessed in this study, it is likely that these patients also make increased demands on other health care services.

“You need to have a high index of suspicion for anxiety and depression, particularly in patients who call frequently,” Dr. Nirenberg said. She says that while the ideal treatments for these nonmotor symptoms of Parkinson's disease have not been established, cognitive-behavioral therapy, anxiolytics, antidepressants, and Parkinson's medications may help. It is also important to be aware that treatment of one of these nonmotor problems might exacerbate another–for example, an SSRI prescribed for depression has the potential to worsen anxiety, she said.

BOSTON – Depression, anxiety, and sleep problems rather than disease explain why some patients with Parkinson's disease call their physicians more frequently than others, according to results of a study presented by Dr. Melissa J. Nirenberg in a poster presentation at the annual meeting of the American Academy of Neurology.

Treating these “invisible” symptoms may both help the patients' quality of life and decrease their health care use, she reported.

In the study, frequent callers–who made an average of 2.4 calls in 100 days–had significantly higher anxiety scores on the Beck Anxiety Inventory and higher depression scores on the Beck Depression Inventory than did those who called infrequently–or a mean of 0.6 calls in 100 days. They also had lower quality of life scores on the Parkinson's Disease Quality of Life scale, reported Dr. Nirenberg. Sleep problems were a universal complaint among frequent callers, but these issues were reported by only 36% of the infrequent callers, a significant difference.

While patients in both groups had moderate motor disability, no differences between groups were found as measured by the motor Unified Parkinson's Disease Rating Scale, Hoehn and Yahr scale, or Schwab and England Disability scale.

The study comprised 44 nondemented Parkinson's disease outpatients who were treated over 4 months in a movement disorders clinic. They all underwent neuropsychiatric and disability testing. Patients who called more than the mean rate of 1.9 calls in 100 days were assigned to the frequent callers group, and those who called less than the mean rate were assigned to the infrequent callers group. Calling history was determined by retrospective chart review.

“These [frequent callers] look good but feel bad,” says Dr. Nirenberg, who is the associate director of the Parkinson's Disease and Movement Disorders Institute at Cornell University, New York. She believes that because anxiety, depression, and sleep disorders are not readily apparent, it might make sense to focus instead on treating the motor symptoms. Even physicians who recognize the importance of the nonmotor symptoms of Parkinson's disease may not have time to ask about them during a routine office visit, and as a result, may be undertreating these symptoms.

Increased telephone health care use has a significant impact on physicians, said Dr. Nirenberg. These calls take up a tremendous amount of the time. While not assessed in this study, it is likely that these patients also make increased demands on other health care services.

“You need to have a high index of suspicion for anxiety and depression, particularly in patients who call frequently,” Dr. Nirenberg said. She says that while the ideal treatments for these nonmotor symptoms of Parkinson's disease have not been established, cognitive-behavioral therapy, anxiolytics, antidepressants, and Parkinson's medications may help. It is also important to be aware that treatment of one of these nonmotor problems might exacerbate another–for example, an SSRI prescribed for depression has the potential to worsen anxiety, she said.

BOSTON – Depression, anxiety, and sleep problems rather than disease explain why some patients with Parkinson's disease call their physicians more frequently than others, according to results of a study presented by Dr. Melissa J. Nirenberg in a poster presentation at the annual meeting of the American Academy of Neurology.

Treating these “invisible” symptoms may both help the patients' quality of life and decrease their health care use, she reported.

In the study, frequent callers–who made an average of 2.4 calls in 100 days–had significantly higher anxiety scores on the Beck Anxiety Inventory and higher depression scores on the Beck Depression Inventory than did those who called infrequently–or a mean of 0.6 calls in 100 days. They also had lower quality of life scores on the Parkinson's Disease Quality of Life scale, reported Dr. Nirenberg. Sleep problems were a universal complaint among frequent callers, but these issues were reported by only 36% of the infrequent callers, a significant difference.

While patients in both groups had moderate motor disability, no differences between groups were found as measured by the motor Unified Parkinson's Disease Rating Scale, Hoehn and Yahr scale, or Schwab and England Disability scale.

The study comprised 44 nondemented Parkinson's disease outpatients who were treated over 4 months in a movement disorders clinic. They all underwent neuropsychiatric and disability testing. Patients who called more than the mean rate of 1.9 calls in 100 days were assigned to the frequent callers group, and those who called less than the mean rate were assigned to the infrequent callers group. Calling history was determined by retrospective chart review.

“These [frequent callers] look good but feel bad,” says Dr. Nirenberg, who is the associate director of the Parkinson's Disease and Movement Disorders Institute at Cornell University, New York. She believes that because anxiety, depression, and sleep disorders are not readily apparent, it might make sense to focus instead on treating the motor symptoms. Even physicians who recognize the importance of the nonmotor symptoms of Parkinson's disease may not have time to ask about them during a routine office visit, and as a result, may be undertreating these symptoms.

Increased telephone health care use has a significant impact on physicians, said Dr. Nirenberg. These calls take up a tremendous amount of the time. While not assessed in this study, it is likely that these patients also make increased demands on other health care services.

“You need to have a high index of suspicion for anxiety and depression, particularly in patients who call frequently,” Dr. Nirenberg said. She says that while the ideal treatments for these nonmotor symptoms of Parkinson's disease have not been established, cognitive-behavioral therapy, anxiolytics, antidepressants, and Parkinson's medications may help. It is also important to be aware that treatment of one of these nonmotor problems might exacerbate another–for example, an SSRI prescribed for depression has the potential to worsen anxiety, she said.