Kerri Wachter

MRL Inc. is recalling AED20 automatic external defibrillators (part No. 972200E) because the devices are susceptible to a malfunction that can prevent delivery of a shock. A complaint of malfunction that resulted in a death in Canada led to the recall.

The malfunction occurs when impact to the exterior of the AED20 causes an internal electrical short, resulting in failure to analyze the patient's heart function. When the malfunction occurs during clinical use, the device displays a “Defib Comm” error message. The company is providing customers with a loaner AED20 at no cost while their unit is serviced. Consumers may call the company at 847-520-0300, extension 153.

MRL Inc. is recalling AED20 automatic external defibrillators (part No. 972200E) because the devices are susceptible to a malfunction that can prevent delivery of a shock. A complaint of malfunction that resulted in a death in Canada led to the recall.

The malfunction occurs when impact to the exterior of the AED20 causes an internal electrical short, resulting in failure to analyze the patient's heart function. When the malfunction occurs during clinical use, the device displays a “Defib Comm” error message. The company is providing customers with a loaner AED20 at no cost while their unit is serviced. Consumers may call the company at 847-520-0300, extension 153.

MRL Inc. is recalling AED20 automatic external defibrillators (part No. 972200E) because the devices are susceptible to a malfunction that can prevent delivery of a shock. A complaint of malfunction that resulted in a death in Canada led to the recall.

The malfunction occurs when impact to the exterior of the AED20 causes an internal electrical short, resulting in failure to analyze the patient's heart function. When the malfunction occurs during clinical use, the device displays a “Defib Comm” error message. The company is providing customers with a loaner AED20 at no cost while their unit is serviced. Consumers may call the company at 847-520-0300, extension 153.

ASHEVILLE, N.C. — Small changes in technique can make a big difference in cesarean section outcomes, which is why it's important to keep up to date with the evidence concerning this procedure, Thomas Ivester, M.D., said at the Southern Obstetric and Gynecologic Seminar.

With an estimated 800,000–1,000,000 C-sections performed in the United States each year, “small improvements in our technique and reductions in morbidity and mortality have a profound effect on the public's health and confer substantial benefits with regard to maternal health,” said Dr. Ivester, of the University of North Carolina at Chapel Hill.

Still, “for a lot of things that we do, we don't really know why we do it. I think that a lot of our specialty is governed by tradition and convention that's just been handed down over the years,” said Dr. Ivester. He offered his thoughts on the existing data for a number of aspects of C-section.

Incision Type

Low transverse incisions (Pfannenstiel, Maylard, Cherney) have a far lower rate of dehiscence than do midline incisions. Good exposure is possible, especially with extension techniques. These incisions are less painful for patients. Low transverse abdominal incisions are appropriate for obese patients, who have complication rates similar to or better than those of patients receiving vertical incisions.

Cautery Use

Minimal cautery use is generally recommended; the assumption is that cauterization devitalizes tissue, hindering the angiogenesis needed for wound repair.

Bladder Flaps

Forming a bladder flap is very commonly done, but there's actually not much data to support it or refute this practice, said Dr. Ivester. In one small study, forming a bladder flap increased operative time by as much as 5 minutes and resulted in a small increase in the amount of blood lost, compared with no bladder flap (Obstet. Gynecol. 2001;98:1089–92).

Blunt vs. Sharp Extension

Data suggest that extension 3 cm beyond the proposed incision occurs less frequently with blunt dissection than with dissection using banded scissors. In addition, sharp dissection appears to lead to slightly greater blood loss and a higher transfusion rate than does blunt dissection.

Placental Delivery

There does not appear to be a difference in the amount of blood loss or in transfusion rates between women who undergo manual extraction versus spontaneous delivery of the placenta. A significant reduction in the rate of endometriosis for women who had spontaneous placental delivery compared with manual extraction has been noted in the literature. Postpartum hemorrhage may occur less frequently with spontaneous delivery, and wound infection rates appear to be lower, too.

Additional Deliveries

Less than 18 months between deliveries increases the risk of uterine rupture by 3–4 times compared with intervals of 18 months or greater, said Dr. Ivester. Ensure that your patients are on appropriate birth control to avoid deliveries less than 18 months apart.

Avoid using a T-incision in cases when an extension is needed to deliver a baby. “You've now interrupted blood flow in two different directions, and you've actually increased the risk of rupture [during subsequent deliveries] to the same degree as with the classic incision,” if not more, he said.

Uterine Repair

The question remains whether to take the uterus out or leave it in. The potential advantages of exteriorization of the uterus include better exposure, decreased blood loss, easier access for uterine massage and inspection of the pelvic nexa, but maternal postoperative and intrapartum discomfort is greater, said Dr. Ivester.

Peritoneal Closure

Peritoneal closure is another hotly debated topic. “There's probably 15%–20% of obstetricians who close the peritoneum, because in their own series, they had a significantly lower risk of adhesion formation,” said Dr. Ivester.

Most of the limited data come from retrospective series, in which it was often hard to tease out who had peritoneal closure. In these small prospective series, patients who did not have peritoneal closure had lower rates of narcotic use, improved bowel function at 24 hours, decreased operative time, and decreased rates of cystitis. There are a number of studies in progress that might shed some light on whether to close the peritoneum.

There is also a question about the choice of suture material. “If you're closing this peritoneum with some highly inflammatory type suture material like chromic, certainly some inflammatory changes or responses may be elicited,” said Dr. Ivester. Switching to something less reactive, such as Vicryl or Monocryl, might be a better choice. Recent evidence from Stanford University demonstrates that closure of the parietal peritoneum resulted in substantially improved rates of adhesion formation for women undergoing cesarean delivery (Obstet. Gynecol. 2005;106:275–80).

Fascia Closure

A number of studies have shown that a continuous running suture works well for fascia closure. Vicryl is an appropriate choice of suture material for a first delivery. Polydioxanone suture is a good choice for obese or diabetic patients. A loop is preferable, because it tends to reduce the number of knots.

The zone of optimal healing is 0.75 mm back from the incision edge. Dr. Ivester recommends working 1 cm back and 1 cm apart with sutures. This provides a balance between optimizing the strength of the repair and allowing space to promote angiogenesis and healing of the incision.

Avoid “postage-stamping” the incision. “You don't necessarily want to be neat. Frequently you'll see—especially in obese patients—it's not the sutures themselves that break. It's this line that's created from this perfectly approximated fascia that looks really beautiful and is really neat. You've basically just created a perforation line like a postage stamp that they rip open the first time they cough or have a good chuckle,” said Dr. Ivester.

The data are mixed on whether to use drains or subcutaneous closure. Some studies have shown significant reductions in wound complications by using drains or subcutaneous closure compared with patients who received neither. Other studies have shown no differences.

“In patients with low platelets or bleeding disorders, drains may be useful, while we tend toward subcutaneous closure in obese women,” Dr. Ivester said.

Antibiotic Use

The debate continues over when to give antibiotics. At Dr. Ivester's hospital antibiotics were previously given on the way to the operating room. Now they are given at cord clamping. The gynecology literature suggests that the best results are obtained when antibiotics are given 30–60 minutes preoperatively. Prophylactic antibiotics (first-generation cephalosporins) have reduced endometritis rates at his hospital.

Wound complications also appear to be lower in the literature for prophylactic antibiotics.

ASHEVILLE, N.C. — Small changes in technique can make a big difference in cesarean section outcomes, which is why it's important to keep up to date with the evidence concerning this procedure, Thomas Ivester, M.D., said at the Southern Obstetric and Gynecologic Seminar.

With an estimated 800,000–1,000,000 C-sections performed in the United States each year, “small improvements in our technique and reductions in morbidity and mortality have a profound effect on the public's health and confer substantial benefits with regard to maternal health,” said Dr. Ivester, of the University of North Carolina at Chapel Hill.

Still, “for a lot of things that we do, we don't really know why we do it. I think that a lot of our specialty is governed by tradition and convention that's just been handed down over the years,” said Dr. Ivester. He offered his thoughts on the existing data for a number of aspects of C-section.

Incision Type

Low transverse incisions (Pfannenstiel, Maylard, Cherney) have a far lower rate of dehiscence than do midline incisions. Good exposure is possible, especially with extension techniques. These incisions are less painful for patients. Low transverse abdominal incisions are appropriate for obese patients, who have complication rates similar to or better than those of patients receiving vertical incisions.

Cautery Use

Minimal cautery use is generally recommended; the assumption is that cauterization devitalizes tissue, hindering the angiogenesis needed for wound repair.

Bladder Flaps

Forming a bladder flap is very commonly done, but there's actually not much data to support it or refute this practice, said Dr. Ivester. In one small study, forming a bladder flap increased operative time by as much as 5 minutes and resulted in a small increase in the amount of blood lost, compared with no bladder flap (Obstet. Gynecol. 2001;98:1089–92).

Blunt vs. Sharp Extension

Data suggest that extension 3 cm beyond the proposed incision occurs less frequently with blunt dissection than with dissection using banded scissors. In addition, sharp dissection appears to lead to slightly greater blood loss and a higher transfusion rate than does blunt dissection.

Placental Delivery

There does not appear to be a difference in the amount of blood loss or in transfusion rates between women who undergo manual extraction versus spontaneous delivery of the placenta. A significant reduction in the rate of endometriosis for women who had spontaneous placental delivery compared with manual extraction has been noted in the literature. Postpartum hemorrhage may occur less frequently with spontaneous delivery, and wound infection rates appear to be lower, too.

Additional Deliveries

Less than 18 months between deliveries increases the risk of uterine rupture by 3–4 times compared with intervals of 18 months or greater, said Dr. Ivester. Ensure that your patients are on appropriate birth control to avoid deliveries less than 18 months apart.

Avoid using a T-incision in cases when an extension is needed to deliver a baby. “You've now interrupted blood flow in two different directions, and you've actually increased the risk of rupture [during subsequent deliveries] to the same degree as with the classic incision,” if not more, he said.

Uterine Repair

The question remains whether to take the uterus out or leave it in. The potential advantages of exteriorization of the uterus include better exposure, decreased blood loss, easier access for uterine massage and inspection of the pelvic nexa, but maternal postoperative and intrapartum discomfort is greater, said Dr. Ivester.

Peritoneal Closure

Peritoneal closure is another hotly debated topic. “There's probably 15%–20% of obstetricians who close the peritoneum, because in their own series, they had a significantly lower risk of adhesion formation,” said Dr. Ivester.

Most of the limited data come from retrospective series, in which it was often hard to tease out who had peritoneal closure. In these small prospective series, patients who did not have peritoneal closure had lower rates of narcotic use, improved bowel function at 24 hours, decreased operative time, and decreased rates of cystitis. There are a number of studies in progress that might shed some light on whether to close the peritoneum.

There is also a question about the choice of suture material. “If you're closing this peritoneum with some highly inflammatory type suture material like chromic, certainly some inflammatory changes or responses may be elicited,” said Dr. Ivester. Switching to something less reactive, such as Vicryl or Monocryl, might be a better choice. Recent evidence from Stanford University demonstrates that closure of the parietal peritoneum resulted in substantially improved rates of adhesion formation for women undergoing cesarean delivery (Obstet. Gynecol. 2005;106:275–80).

Fascia Closure

A number of studies have shown that a continuous running suture works well for fascia closure. Vicryl is an appropriate choice of suture material for a first delivery. Polydioxanone suture is a good choice for obese or diabetic patients. A loop is preferable, because it tends to reduce the number of knots.

The zone of optimal healing is 0.75 mm back from the incision edge. Dr. Ivester recommends working 1 cm back and 1 cm apart with sutures. This provides a balance between optimizing the strength of the repair and allowing space to promote angiogenesis and healing of the incision.

Avoid “postage-stamping” the incision. “You don't necessarily want to be neat. Frequently you'll see—especially in obese patients—it's not the sutures themselves that break. It's this line that's created from this perfectly approximated fascia that looks really beautiful and is really neat. You've basically just created a perforation line like a postage stamp that they rip open the first time they cough or have a good chuckle,” said Dr. Ivester.

The data are mixed on whether to use drains or subcutaneous closure. Some studies have shown significant reductions in wound complications by using drains or subcutaneous closure compared with patients who received neither. Other studies have shown no differences.

“In patients with low platelets or bleeding disorders, drains may be useful, while we tend toward subcutaneous closure in obese women,” Dr. Ivester said.

Antibiotic Use

The debate continues over when to give antibiotics. At Dr. Ivester's hospital antibiotics were previously given on the way to the operating room. Now they are given at cord clamping. The gynecology literature suggests that the best results are obtained when antibiotics are given 30–60 minutes preoperatively. Prophylactic antibiotics (first-generation cephalosporins) have reduced endometritis rates at his hospital.

Wound complications also appear to be lower in the literature for prophylactic antibiotics.

ASHEVILLE, N.C. — Small changes in technique can make a big difference in cesarean section outcomes, which is why it's important to keep up to date with the evidence concerning this procedure, Thomas Ivester, M.D., said at the Southern Obstetric and Gynecologic Seminar.

With an estimated 800,000–1,000,000 C-sections performed in the United States each year, “small improvements in our technique and reductions in morbidity and mortality have a profound effect on the public's health and confer substantial benefits with regard to maternal health,” said Dr. Ivester, of the University of North Carolina at Chapel Hill.

Still, “for a lot of things that we do, we don't really know why we do it. I think that a lot of our specialty is governed by tradition and convention that's just been handed down over the years,” said Dr. Ivester. He offered his thoughts on the existing data for a number of aspects of C-section.

Incision Type

Low transverse incisions (Pfannenstiel, Maylard, Cherney) have a far lower rate of dehiscence than do midline incisions. Good exposure is possible, especially with extension techniques. These incisions are less painful for patients. Low transverse abdominal incisions are appropriate for obese patients, who have complication rates similar to or better than those of patients receiving vertical incisions.

Cautery Use

Minimal cautery use is generally recommended; the assumption is that cauterization devitalizes tissue, hindering the angiogenesis needed for wound repair.

Bladder Flaps

Forming a bladder flap is very commonly done, but there's actually not much data to support it or refute this practice, said Dr. Ivester. In one small study, forming a bladder flap increased operative time by as much as 5 minutes and resulted in a small increase in the amount of blood lost, compared with no bladder flap (Obstet. Gynecol. 2001;98:1089–92).

Blunt vs. Sharp Extension

Data suggest that extension 3 cm beyond the proposed incision occurs less frequently with blunt dissection than with dissection using banded scissors. In addition, sharp dissection appears to lead to slightly greater blood loss and a higher transfusion rate than does blunt dissection.

Placental Delivery

There does not appear to be a difference in the amount of blood loss or in transfusion rates between women who undergo manual extraction versus spontaneous delivery of the placenta. A significant reduction in the rate of endometriosis for women who had spontaneous placental delivery compared with manual extraction has been noted in the literature. Postpartum hemorrhage may occur less frequently with spontaneous delivery, and wound infection rates appear to be lower, too.

Additional Deliveries

Less than 18 months between deliveries increases the risk of uterine rupture by 3–4 times compared with intervals of 18 months or greater, said Dr. Ivester. Ensure that your patients are on appropriate birth control to avoid deliveries less than 18 months apart.

Avoid using a T-incision in cases when an extension is needed to deliver a baby. “You've now interrupted blood flow in two different directions, and you've actually increased the risk of rupture [during subsequent deliveries] to the same degree as with the classic incision,” if not more, he said.

Uterine Repair

The question remains whether to take the uterus out or leave it in. The potential advantages of exteriorization of the uterus include better exposure, decreased blood loss, easier access for uterine massage and inspection of the pelvic nexa, but maternal postoperative and intrapartum discomfort is greater, said Dr. Ivester.

Peritoneal Closure

Peritoneal closure is another hotly debated topic. “There's probably 15%–20% of obstetricians who close the peritoneum, because in their own series, they had a significantly lower risk of adhesion formation,” said Dr. Ivester.

Most of the limited data come from retrospective series, in which it was often hard to tease out who had peritoneal closure. In these small prospective series, patients who did not have peritoneal closure had lower rates of narcotic use, improved bowel function at 24 hours, decreased operative time, and decreased rates of cystitis. There are a number of studies in progress that might shed some light on whether to close the peritoneum.

There is also a question about the choice of suture material. “If you're closing this peritoneum with some highly inflammatory type suture material like chromic, certainly some inflammatory changes or responses may be elicited,” said Dr. Ivester. Switching to something less reactive, such as Vicryl or Monocryl, might be a better choice. Recent evidence from Stanford University demonstrates that closure of the parietal peritoneum resulted in substantially improved rates of adhesion formation for women undergoing cesarean delivery (Obstet. Gynecol. 2005;106:275–80).

Fascia Closure

A number of studies have shown that a continuous running suture works well for fascia closure. Vicryl is an appropriate choice of suture material for a first delivery. Polydioxanone suture is a good choice for obese or diabetic patients. A loop is preferable, because it tends to reduce the number of knots.

The zone of optimal healing is 0.75 mm back from the incision edge. Dr. Ivester recommends working 1 cm back and 1 cm apart with sutures. This provides a balance between optimizing the strength of the repair and allowing space to promote angiogenesis and healing of the incision.

Avoid “postage-stamping” the incision. “You don't necessarily want to be neat. Frequently you'll see—especially in obese patients—it's not the sutures themselves that break. It's this line that's created from this perfectly approximated fascia that looks really beautiful and is really neat. You've basically just created a perforation line like a postage stamp that they rip open the first time they cough or have a good chuckle,” said Dr. Ivester.

The data are mixed on whether to use drains or subcutaneous closure. Some studies have shown significant reductions in wound complications by using drains or subcutaneous closure compared with patients who received neither. Other studies have shown no differences.

“In patients with low platelets or bleeding disorders, drains may be useful, while we tend toward subcutaneous closure in obese women,” Dr. Ivester said.

Antibiotic Use

The debate continues over when to give antibiotics. At Dr. Ivester's hospital antibiotics were previously given on the way to the operating room. Now they are given at cord clamping. The gynecology literature suggests that the best results are obtained when antibiotics are given 30–60 minutes preoperatively. Prophylactic antibiotics (first-generation cephalosporins) have reduced endometritis rates at his hospital.

Wound complications also appear to be lower in the literature for prophylactic antibiotics.

ASHEVILLE, N.C. — Peripartum hemorrhage is one of the leading causes of maternal mortality, making it important to understand the myriad options for controlling bleeding, David C. Mayer, M.D., said at the Southern Obstetric and Gynecologic Seminar.

“Unfortunately, over the decades, hemorrhage has never been moved out of the top three causes of maternal mortality,” said Dr. Mayer of the department of anesthesiology at the University of North Carolina at Chapel Hill.

Peripartum hemorrhage accounts for as much as 18% of pregnancy-related deaths in the United States, according to one estimate.

Resuscitation is the first goal in the management of peripartum hemorrhage (PPH). Make sure there is an adequate number of intravenous lines and maintain adequate volume by using crystalloids, colloids, packed red blood cells, fresh frozen plasma, or platelets, as necessary. Get baseline blood laboratory tests, including a coagulation profile, and monitor arterial blood gas levels and urinary output. Invasive monitoring with arterial or central venous lines may be necessary, as may consultation with specialists, cautioned Dr. Mayer.

There are a number of options to control bleeding: pharmacologic (such as prostaglandins), autologous blood transfusion, and selective arterial embolization. Pharmacologic therapy includes oxytocics, ergot alkaloids, prostaglandins, and recombinant activated factor VII (rFVIIa). Keep in mind almost all studies of pharmacologic therapies are based on routine elective cesarean sections.

“It may have very little applicability to a patient with an atonic uterus,” Dr. Mayer said.

Oxytocin (Pitocin) is the pharmacologic therapy that most obstetricians go to first to control bleeding. The drug can be used as prophylaxis in women who are at high risk for PPH, with doses of 10–40 U/L administered intravenously. “For uterine atony, I'm very aggressive with oxytocin, except for giving a large bolus,” Dr. Mayer said during the meeting.

He recommends using up to 40–60 U/L given intravenously. Avoid using an intravenous bolus greater than 2 IU. A bolus less than 2 IU can be effective and is unlikely to be problematic, especially if blood pressure is supported. “Just remember that if your patient is already hypotensive, it's probably not the thing to do—increasing the rate of oxytocin,” said Dr. Mayer, also of the department of obstetrics and gynecology at the university.

Ergot alkaloids—ergonovine and methylergonovine—are very effective at inducing contractions. While the exact mechanism of action is unclear, ergot alkaloids are believed to have adrenergic, dopaminergic, and tryptaminergic effects. “Most people now think that it's the adrenergic effect that causes the increased uterine contractility,” Dr. Mayer said.

However, it's also thought that the adrenergic effect is responsible for some of the concerning side effects. Ergot alkaloids produce vasoconstriction that can last for 1–4 hours. These drugs are associated with hypertension, increased central blood volume, coronary vasospasm, pulmonary edema, and cerebrovascular accidents. The dopaminergic stimulation produces nausea and vomiting that can be severe in about 20% of patients. Ergot alkaloids should be given in a very controlled manner to avoid complications such as vasospasm and decreased ejection fractions.

The range of options in the prostaglandin family could grow in the future. “We don't have the whole armamentarium that they do in Europe and I think that someday we may,” Dr. Mayer said. Prostaglandins available in the United States include carboprost (15-methyl prostaglandin F_2α), misoprostol (prostaglandin E₁), dinoprost (prostaglandin F_2α), and dinoprostone (prostaglandin E₂).

The side effect profile for these drugs is different from that of the oxytocics or ergot alkaloids. Prostaglandins do not contribute to significant vasoconstriction. One big drawback for these drugs is that they cannot be administered intravenously. Instead, prostaglandins can be administered intramuscularly and intramyometrially. Prostaglandins E₁ and E₂ also can be administered orally, vaginally, or rectally.

“There's nothing to suggest that there's a better drug than carboprost,” Dr. Mayer said. Carboprost (Hemabate) is 10 times more potent than the parent compound (prostaglandin F_2α). It has minimal effect on the cardiovascular system. Severe bronchial constriction is the one real problem associated with carboprost, even in patients without asthma. This can result in bronchospasm, regional ventilation perfusion mismatch, and arterial desaturation. Patients receiving carboprost should be monitored with a pulse oximeter until at least an hour after the last dose. Dosing is 250 mcg given every 15 to 45 minutes, up to a maximum of 8 doses.

Both carboprost and methylergonovine are contraindicated in patients with cardiovascular and respiratory problems. Misoprostol—a synthetic oral prostaglandin E₁ analog—may be one option for these patients. “Misoprostol plays a major role in [the management of] peripartum hemorrhage,” Dr. Mayer said. It is not associated with bronchospasm, has no major cardiovascular effects, and can be stored for a long time without refrigeration.

Based on the literature, the evidence is not sufficient at this time to support routine use of misoprostol for the prevention of PPH. “The drug has such a high safety profile that it may be more useful in a treatment role” said Dr. Mayer. He recommends using 800–1,000 mcg administered rectally.

Many PPH cases have a major component of acquired coagulopathy, making rFVIIa (Novoseven) a treatment option, indicated for hemophilia A or B, with inhibitors of factor VII or factor IX. The drug induces hemostasis independent of factor VII or IX. It complexes with tissue factor to promote the conversion of factor IX to factor IXa, factor X to factor Xa, and prothrombin to thrombin—the key parts of the coagulation cascade. The drug produces clots, making it theoretically contraindicated in patients with disseminated intravascular coagulopathy.

The literature on the use of rFVIIa for PPH has been encouraging so far. In a recent study, 12 patients with severe PPH (estimated blood loss of 5–25 L) were treated with the drug (Br. J. Anaesth. 2005;94:592–5). All had previously undergone surgery, and one-third had arterial ligation. Eleven patients had a positive response.

“They're feeling was to give the drug at 1.5 L blood volume loss—it buys time,” said Dr. Mayer.

However, the drug is very expensive. The cost equivalent of a single 90-mcg/kg dose is 50 units of packed red blood cells, 2 days in the ICU, or an embolization procedure. In patients for whom surgical options have been explored, for whom there are no vascular interventional radiology options, for whom significant blood products are required, and for whom results of the coagulation studies are elevated, “this is a very reasonable drug to give,” Dr. Mayer said.

Intraoperative autologous transfusion should be considered when there is major blood loss and an inadequate amount of packed red blood cells is available. Potential risks associated with obstetric use include amniotic fluid embolism and maternal exposure to fetal red cells. However, in 400 exposures to intraoperative autologous transfusion, there has been only one case of amniotic fluid embolism that was not confirmed pathologically. Heparin toxicity also has been associated with the technique.

At the University of North Carolina at Chapel Hill, the cell saver has been used for 12 obstetric patients. “It's a perfect solution for Jehovah's Witnesses with risk factors, such as a known placenta percreta,” said Dr. Mayer. Blood was autotransfused in only one case though. This patient received 1,200 mL of salvaged blood with no problems.

Selective arterial embolization is highly successful when it can be performed. There are very few complications—fever is the most common. The technique also can be used prophylactically using a balloon. Coagulopathy is not a contraindication, so it's a good option for these patients.

ASHEVILLE, N.C. — Peripartum hemorrhage is one of the leading causes of maternal mortality, making it important to understand the myriad options for controlling bleeding, David C. Mayer, M.D., said at the Southern Obstetric and Gynecologic Seminar.

“Unfortunately, over the decades, hemorrhage has never been moved out of the top three causes of maternal mortality,” said Dr. Mayer of the department of anesthesiology at the University of North Carolina at Chapel Hill.

Peripartum hemorrhage accounts for as much as 18% of pregnancy-related deaths in the United States, according to one estimate.

Resuscitation is the first goal in the management of peripartum hemorrhage (PPH). Make sure there is an adequate number of intravenous lines and maintain adequate volume by using crystalloids, colloids, packed red blood cells, fresh frozen plasma, or platelets, as necessary. Get baseline blood laboratory tests, including a coagulation profile, and monitor arterial blood gas levels and urinary output. Invasive monitoring with arterial or central venous lines may be necessary, as may consultation with specialists, cautioned Dr. Mayer.

There are a number of options to control bleeding: pharmacologic (such as prostaglandins), autologous blood transfusion, and selective arterial embolization. Pharmacologic therapy includes oxytocics, ergot alkaloids, prostaglandins, and recombinant activated factor VII (rFVIIa). Keep in mind almost all studies of pharmacologic therapies are based on routine elective cesarean sections.

“It may have very little applicability to a patient with an atonic uterus,” Dr. Mayer said.

Oxytocin (Pitocin) is the pharmacologic therapy that most obstetricians go to first to control bleeding. The drug can be used as prophylaxis in women who are at high risk for PPH, with doses of 10–40 U/L administered intravenously. “For uterine atony, I'm very aggressive with oxytocin, except for giving a large bolus,” Dr. Mayer said during the meeting.

He recommends using up to 40–60 U/L given intravenously. Avoid using an intravenous bolus greater than 2 IU. A bolus less than 2 IU can be effective and is unlikely to be problematic, especially if blood pressure is supported. “Just remember that if your patient is already hypotensive, it's probably not the thing to do—increasing the rate of oxytocin,” said Dr. Mayer, also of the department of obstetrics and gynecology at the university.

Ergot alkaloids—ergonovine and methylergonovine—are very effective at inducing contractions. While the exact mechanism of action is unclear, ergot alkaloids are believed to have adrenergic, dopaminergic, and tryptaminergic effects. “Most people now think that it's the adrenergic effect that causes the increased uterine contractility,” Dr. Mayer said.

However, it's also thought that the adrenergic effect is responsible for some of the concerning side effects. Ergot alkaloids produce vasoconstriction that can last for 1–4 hours. These drugs are associated with hypertension, increased central blood volume, coronary vasospasm, pulmonary edema, and cerebrovascular accidents. The dopaminergic stimulation produces nausea and vomiting that can be severe in about 20% of patients. Ergot alkaloids should be given in a very controlled manner to avoid complications such as vasospasm and decreased ejection fractions.

The range of options in the prostaglandin family could grow in the future. “We don't have the whole armamentarium that they do in Europe and I think that someday we may,” Dr. Mayer said. Prostaglandins available in the United States include carboprost (15-methyl prostaglandin F_2α), misoprostol (prostaglandin E₁), dinoprost (prostaglandin F_2α), and dinoprostone (prostaglandin E₂).

The side effect profile for these drugs is different from that of the oxytocics or ergot alkaloids. Prostaglandins do not contribute to significant vasoconstriction. One big drawback for these drugs is that they cannot be administered intravenously. Instead, prostaglandins can be administered intramuscularly and intramyometrially. Prostaglandins E₁ and E₂ also can be administered orally, vaginally, or rectally.

“There's nothing to suggest that there's a better drug than carboprost,” Dr. Mayer said. Carboprost (Hemabate) is 10 times more potent than the parent compound (prostaglandin F_2α). It has minimal effect on the cardiovascular system. Severe bronchial constriction is the one real problem associated with carboprost, even in patients without asthma. This can result in bronchospasm, regional ventilation perfusion mismatch, and arterial desaturation. Patients receiving carboprost should be monitored with a pulse oximeter until at least an hour after the last dose. Dosing is 250 mcg given every 15 to 45 minutes, up to a maximum of 8 doses.

Both carboprost and methylergonovine are contraindicated in patients with cardiovascular and respiratory problems. Misoprostol—a synthetic oral prostaglandin E₁ analog—may be one option for these patients. “Misoprostol plays a major role in [the management of] peripartum hemorrhage,” Dr. Mayer said. It is not associated with bronchospasm, has no major cardiovascular effects, and can be stored for a long time without refrigeration.

Based on the literature, the evidence is not sufficient at this time to support routine use of misoprostol for the prevention of PPH. “The drug has such a high safety profile that it may be more useful in a treatment role” said Dr. Mayer. He recommends using 800–1,000 mcg administered rectally.

Many PPH cases have a major component of acquired coagulopathy, making rFVIIa (Novoseven) a treatment option, indicated for hemophilia A or B, with inhibitors of factor VII or factor IX. The drug induces hemostasis independent of factor VII or IX. It complexes with tissue factor to promote the conversion of factor IX to factor IXa, factor X to factor Xa, and prothrombin to thrombin—the key parts of the coagulation cascade. The drug produces clots, making it theoretically contraindicated in patients with disseminated intravascular coagulopathy.

The literature on the use of rFVIIa for PPH has been encouraging so far. In a recent study, 12 patients with severe PPH (estimated blood loss of 5–25 L) were treated with the drug (Br. J. Anaesth. 2005;94:592–5). All had previously undergone surgery, and one-third had arterial ligation. Eleven patients had a positive response.

“They're feeling was to give the drug at 1.5 L blood volume loss—it buys time,” said Dr. Mayer.

However, the drug is very expensive. The cost equivalent of a single 90-mcg/kg dose is 50 units of packed red blood cells, 2 days in the ICU, or an embolization procedure. In patients for whom surgical options have been explored, for whom there are no vascular interventional radiology options, for whom significant blood products are required, and for whom results of the coagulation studies are elevated, “this is a very reasonable drug to give,” Dr. Mayer said.

Intraoperative autologous transfusion should be considered when there is major blood loss and an inadequate amount of packed red blood cells is available. Potential risks associated with obstetric use include amniotic fluid embolism and maternal exposure to fetal red cells. However, in 400 exposures to intraoperative autologous transfusion, there has been only one case of amniotic fluid embolism that was not confirmed pathologically. Heparin toxicity also has been associated with the technique.

At the University of North Carolina at Chapel Hill, the cell saver has been used for 12 obstetric patients. “It's a perfect solution for Jehovah's Witnesses with risk factors, such as a known placenta percreta,” said Dr. Mayer. Blood was autotransfused in only one case though. This patient received 1,200 mL of salvaged blood with no problems.

Selective arterial embolization is highly successful when it can be performed. There are very few complications—fever is the most common. The technique also can be used prophylactically using a balloon. Coagulopathy is not a contraindication, so it's a good option for these patients.

ASHEVILLE, N.C. — Peripartum hemorrhage is one of the leading causes of maternal mortality, making it important to understand the myriad options for controlling bleeding, David C. Mayer, M.D., said at the Southern Obstetric and Gynecologic Seminar.

“Unfortunately, over the decades, hemorrhage has never been moved out of the top three causes of maternal mortality,” said Dr. Mayer of the department of anesthesiology at the University of North Carolina at Chapel Hill.

Peripartum hemorrhage accounts for as much as 18% of pregnancy-related deaths in the United States, according to one estimate.

Resuscitation is the first goal in the management of peripartum hemorrhage (PPH). Make sure there is an adequate number of intravenous lines and maintain adequate volume by using crystalloids, colloids, packed red blood cells, fresh frozen plasma, or platelets, as necessary. Get baseline blood laboratory tests, including a coagulation profile, and monitor arterial blood gas levels and urinary output. Invasive monitoring with arterial or central venous lines may be necessary, as may consultation with specialists, cautioned Dr. Mayer.

There are a number of options to control bleeding: pharmacologic (such as prostaglandins), autologous blood transfusion, and selective arterial embolization. Pharmacologic therapy includes oxytocics, ergot alkaloids, prostaglandins, and recombinant activated factor VII (rFVIIa). Keep in mind almost all studies of pharmacologic therapies are based on routine elective cesarean sections.

“It may have very little applicability to a patient with an atonic uterus,” Dr. Mayer said.

Oxytocin (Pitocin) is the pharmacologic therapy that most obstetricians go to first to control bleeding. The drug can be used as prophylaxis in women who are at high risk for PPH, with doses of 10–40 U/L administered intravenously. “For uterine atony, I'm very aggressive with oxytocin, except for giving a large bolus,” Dr. Mayer said during the meeting.

He recommends using up to 40–60 U/L given intravenously. Avoid using an intravenous bolus greater than 2 IU. A bolus less than 2 IU can be effective and is unlikely to be problematic, especially if blood pressure is supported. “Just remember that if your patient is already hypotensive, it's probably not the thing to do—increasing the rate of oxytocin,” said Dr. Mayer, also of the department of obstetrics and gynecology at the university.

Ergot alkaloids—ergonovine and methylergonovine—are very effective at inducing contractions. While the exact mechanism of action is unclear, ergot alkaloids are believed to have adrenergic, dopaminergic, and tryptaminergic effects. “Most people now think that it's the adrenergic effect that causes the increased uterine contractility,” Dr. Mayer said.

However, it's also thought that the adrenergic effect is responsible for some of the concerning side effects. Ergot alkaloids produce vasoconstriction that can last for 1–4 hours. These drugs are associated with hypertension, increased central blood volume, coronary vasospasm, pulmonary edema, and cerebrovascular accidents. The dopaminergic stimulation produces nausea and vomiting that can be severe in about 20% of patients. Ergot alkaloids should be given in a very controlled manner to avoid complications such as vasospasm and decreased ejection fractions.

The range of options in the prostaglandin family could grow in the future. “We don't have the whole armamentarium that they do in Europe and I think that someday we may,” Dr. Mayer said. Prostaglandins available in the United States include carboprost (15-methyl prostaglandin F_2α), misoprostol (prostaglandin E₁), dinoprost (prostaglandin F_2α), and dinoprostone (prostaglandin E₂).

The side effect profile for these drugs is different from that of the oxytocics or ergot alkaloids. Prostaglandins do not contribute to significant vasoconstriction. One big drawback for these drugs is that they cannot be administered intravenously. Instead, prostaglandins can be administered intramuscularly and intramyometrially. Prostaglandins E₁ and E₂ also can be administered orally, vaginally, or rectally.

“There's nothing to suggest that there's a better drug than carboprost,” Dr. Mayer said. Carboprost (Hemabate) is 10 times more potent than the parent compound (prostaglandin F_2α). It has minimal effect on the cardiovascular system. Severe bronchial constriction is the one real problem associated with carboprost, even in patients without asthma. This can result in bronchospasm, regional ventilation perfusion mismatch, and arterial desaturation. Patients receiving carboprost should be monitored with a pulse oximeter until at least an hour after the last dose. Dosing is 250 mcg given every 15 to 45 minutes, up to a maximum of 8 doses.

Both carboprost and methylergonovine are contraindicated in patients with cardiovascular and respiratory problems. Misoprostol—a synthetic oral prostaglandin E₁ analog—may be one option for these patients. “Misoprostol plays a major role in [the management of] peripartum hemorrhage,” Dr. Mayer said. It is not associated with bronchospasm, has no major cardiovascular effects, and can be stored for a long time without refrigeration.

Based on the literature, the evidence is not sufficient at this time to support routine use of misoprostol for the prevention of PPH. “The drug has such a high safety profile that it may be more useful in a treatment role” said Dr. Mayer. He recommends using 800–1,000 mcg administered rectally.

Many PPH cases have a major component of acquired coagulopathy, making rFVIIa (Novoseven) a treatment option, indicated for hemophilia A or B, with inhibitors of factor VII or factor IX. The drug induces hemostasis independent of factor VII or IX. It complexes with tissue factor to promote the conversion of factor IX to factor IXa, factor X to factor Xa, and prothrombin to thrombin—the key parts of the coagulation cascade. The drug produces clots, making it theoretically contraindicated in patients with disseminated intravascular coagulopathy.

The literature on the use of rFVIIa for PPH has been encouraging so far. In a recent study, 12 patients with severe PPH (estimated blood loss of 5–25 L) were treated with the drug (Br. J. Anaesth. 2005;94:592–5). All had previously undergone surgery, and one-third had arterial ligation. Eleven patients had a positive response.

“They're feeling was to give the drug at 1.5 L blood volume loss—it buys time,” said Dr. Mayer.

However, the drug is very expensive. The cost equivalent of a single 90-mcg/kg dose is 50 units of packed red blood cells, 2 days in the ICU, or an embolization procedure. In patients for whom surgical options have been explored, for whom there are no vascular interventional radiology options, for whom significant blood products are required, and for whom results of the coagulation studies are elevated, “this is a very reasonable drug to give,” Dr. Mayer said.

Intraoperative autologous transfusion should be considered when there is major blood loss and an inadequate amount of packed red blood cells is available. Potential risks associated with obstetric use include amniotic fluid embolism and maternal exposure to fetal red cells. However, in 400 exposures to intraoperative autologous transfusion, there has been only one case of amniotic fluid embolism that was not confirmed pathologically. Heparin toxicity also has been associated with the technique.

At the University of North Carolina at Chapel Hill, the cell saver has been used for 12 obstetric patients. “It's a perfect solution for Jehovah's Witnesses with risk factors, such as a known placenta percreta,” said Dr. Mayer. Blood was autotransfused in only one case though. This patient received 1,200 mL of salvaged blood with no problems.

Selective arterial embolization is highly successful when it can be performed. There are very few complications—fever is the most common. The technique also can be used prophylactically using a balloon. Coagulopathy is not a contraindication, so it's a good option for these patients.

“Cerebral palsy is not really the diagnosis. It is a descriptor of the child's motor function … the real push is to understand the factor or factors underlying the development of cerebral palsy,” said Alexander H. Hoon Jr., M.D., director of the Phelps Center for Cerebral Palsy and Neurodevelopmental Medicine at the Kennedy Krieger Institute in Baltimore.

Cerebral palsy falls into broad etiologic groups: disorders of early brain formation, injury associated with prematurity (periventricular leukomalacia), neonatal encephalopathies, and a heterogeneous group of postnatal disorders. Approximately 30% of cerebral palsy cases are associated with brain malformations, 40% with prematurity, 20% with neonatal encephalopathies, and 10% with postnatal causes—with some regional epidemiologic variability.

Conventional MR imaging and diffusion tensor imaging (DTI) can be used together to establish an etiology and to refine the classification of cerebral palsy. “The importance of establishing an etiology is to use this information to refine therapy, and improve understanding of prognosis and recurrence risk,” said Dr. Hoon. MRI established the diagnosis of periventricular leukomalacia in the child evaluated for spastic quadriplegic cerebral palsy. The DTI images—acquired under a research protocol to refine understanding of pathogenesis and classification—revealed abnormalities in both motor and sensory pathways.

Significant delays in the acquisition of motor skills make clinicians suspect cerebral palsy. For a child with severe cerebral palsy, the disease is usually evident within the first 6–12 months of life; and for a moderately affected child by 1–2 years of age, said Dr. Hoon. For a mildly affected child, clinicians typically wait as long as possible to see if the child develops independent ambulation.

Any child with cerebral palsy should be imaged, he said. Once the diagnosis of cerebral palsy is established, conventional MRI is part of the routine work-up to classify children with cerebral palsy more precisely than by clinical exam. By pinpointing the cause, clinicians can make certain inferences about recurrence risk, and to some extent prognosis, said Dr. Hoon.

MRI also can be useful for children in a gray zone—for whom it's uncertain whether they will develop cerebral palsy. If the MRI appears normal, parents can be reassured, with the caveat from the neurologist that ongoing follow-up is important. It's less clear whether to image children with milder delays but who appear clinically to have a good prognosis.

On MRI, clinicians look for evidence associated with brain malformation, white matter disorder associated with prematurity, injury that occurred in a term infant, or postnatal causes including genetic or metabolic disease. Up to 70%–90% of children with cerebral palsy will have an abnormal MRI. “It's a very helpful diagnostic test,” said Dr. Hoon. For example, cerebral palsy with a normal MRI would suggest other possible causes, including a treatable disorder called dopa responsive dystonia.

DTI reveals abnormalities in white matter tracts by using the diffusion of water along the longitudinal direction of the axons in the tracts. Within white matter, water moves parallel to tracts. Conventional MRI can distinguish white from gray matter but can provide very little detail about the white matter; MRI cannot reveal or quantify specific fiber tract directions.

DTI relies on the principle that water diffusion—or brownian motion—is affected by the properties of the medium in which it occurs. Diffusion within biologic tissues reflects tissue structure and architecture at the microscopic level. DTI allows researchers to look at brain structures that were previously not visible in vivo, he said.

At the Kennedy Krieger Institute, DTI is used in research to evaluate 26 brain white matter tracts in much greater detail to look for abnormalities—small size or absence. Visualizing individual tracts of white matter is only part of the problem. At the moment, researchers don't know exactly what normal tracts look like nor do they know how function correlates with specific tracts.

Dr. Hoon and his colleagues are currently studying the white matter tracts of 30 children born prematurely at various gestational ages, with the goal of correlating tract abnormalities with clinical measures of the child's motor and sensory function. “We're at the very beginning of this process,” said Dr. Hoon.

Once function can be correlated with specific tracts, researchers would then be able to use DTI to establish specific therapies for abnormalities associated with each tract. While DTI is still largely a research tool for cerebral palsy, many MRI scanners have the capacity to perform DT scans.

MR and DT imaging do not pose any risk to children, but there is some risk associated with anesthesia. Young children are typically sedated with chloral hydrate or intravenous sedation to minimize movement in the MR machine and generally do well. In older children with more significant movement, anesthesia may be necessary, which poses some risk, said Dr. Hoon.

Shown are axial MRIs of children with, left to right, holoprosencephaly (brain malformation), schizencephaly (brain malformation), periventricular leukomalacia (prematurity), and hypoxic-ischemic encephalopathy (neonatal encephalopathy).

Axial diffusion tensor images of the same children as above, in the same order as above, reveal white matter tracts oriented in the plane of the image (shown in blue), up and down (shown in green), and left to right (shown in red). Photos courtesy Dr. Susumu Mori and Dr. Lidia Nagae-Poetscher

“Cerebral palsy is not really the diagnosis. It is a descriptor of the child's motor function … the real push is to understand the factor or factors underlying the development of cerebral palsy,” said Alexander H. Hoon Jr., M.D., director of the Phelps Center for Cerebral Palsy and Neurodevelopmental Medicine at the Kennedy Krieger Institute in Baltimore.

Cerebral palsy falls into broad etiologic groups: disorders of early brain formation, injury associated with prematurity (periventricular leukomalacia), neonatal encephalopathies, and a heterogeneous group of postnatal disorders. Approximately 30% of cerebral palsy cases are associated with brain malformations, 40% with prematurity, 20% with neonatal encephalopathies, and 10% with postnatal causes—with some regional epidemiologic variability.

Conventional MR imaging and diffusion tensor imaging (DTI) can be used together to establish an etiology and to refine the classification of cerebral palsy. “The importance of establishing an etiology is to use this information to refine therapy, and improve understanding of prognosis and recurrence risk,” said Dr. Hoon. MRI established the diagnosis of periventricular leukomalacia in the child evaluated for spastic quadriplegic cerebral palsy. The DTI images—acquired under a research protocol to refine understanding of pathogenesis and classification—revealed abnormalities in both motor and sensory pathways.

Significant delays in the acquisition of motor skills make clinicians suspect cerebral palsy. For a child with severe cerebral palsy, the disease is usually evident within the first 6–12 months of life; and for a moderately affected child by 1–2 years of age, said Dr. Hoon. For a mildly affected child, clinicians typically wait as long as possible to see if the child develops independent ambulation.

Any child with cerebral palsy should be imaged, he said. Once the diagnosis of cerebral palsy is established, conventional MRI is part of the routine work-up to classify children with cerebral palsy more precisely than by clinical exam. By pinpointing the cause, clinicians can make certain inferences about recurrence risk, and to some extent prognosis, said Dr. Hoon.

MRI also can be useful for children in a gray zone—for whom it's uncertain whether they will develop cerebral palsy. If the MRI appears normal, parents can be reassured, with the caveat from the neurologist that ongoing follow-up is important. It's less clear whether to image children with milder delays but who appear clinically to have a good prognosis.

On MRI, clinicians look for evidence associated with brain malformation, white matter disorder associated with prematurity, injury that occurred in a term infant, or postnatal causes including genetic or metabolic disease. Up to 70%–90% of children with cerebral palsy will have an abnormal MRI. “It's a very helpful diagnostic test,” said Dr. Hoon. For example, cerebral palsy with a normal MRI would suggest other possible causes, including a treatable disorder called dopa responsive dystonia.

DTI reveals abnormalities in white matter tracts by using the diffusion of water along the longitudinal direction of the axons in the tracts. Within white matter, water moves parallel to tracts. Conventional MRI can distinguish white from gray matter but can provide very little detail about the white matter; MRI cannot reveal or quantify specific fiber tract directions.

DTI relies on the principle that water diffusion—or brownian motion—is affected by the properties of the medium in which it occurs. Diffusion within biologic tissues reflects tissue structure and architecture at the microscopic level. DTI allows researchers to look at brain structures that were previously not visible in vivo, he said.

At the Kennedy Krieger Institute, DTI is used in research to evaluate 26 brain white matter tracts in much greater detail to look for abnormalities—small size or absence. Visualizing individual tracts of white matter is only part of the problem. At the moment, researchers don't know exactly what normal tracts look like nor do they know how function correlates with specific tracts.

Dr. Hoon and his colleagues are currently studying the white matter tracts of 30 children born prematurely at various gestational ages, with the goal of correlating tract abnormalities with clinical measures of the child's motor and sensory function. “We're at the very beginning of this process,” said Dr. Hoon.

Once function can be correlated with specific tracts, researchers would then be able to use DTI to establish specific therapies for abnormalities associated with each tract. While DTI is still largely a research tool for cerebral palsy, many MRI scanners have the capacity to perform DT scans.

MR and DT imaging do not pose any risk to children, but there is some risk associated with anesthesia. Young children are typically sedated with chloral hydrate or intravenous sedation to minimize movement in the MR machine and generally do well. In older children with more significant movement, anesthesia may be necessary, which poses some risk, said Dr. Hoon.

Shown are axial MRIs of children with, left to right, holoprosencephaly (brain malformation), schizencephaly (brain malformation), periventricular leukomalacia (prematurity), and hypoxic-ischemic encephalopathy (neonatal encephalopathy).

Axial diffusion tensor images of the same children as above, in the same order as above, reveal white matter tracts oriented in the plane of the image (shown in blue), up and down (shown in green), and left to right (shown in red). Photos courtesy Dr. Susumu Mori and Dr. Lidia Nagae-Poetscher

“Cerebral palsy is not really the diagnosis. It is a descriptor of the child's motor function … the real push is to understand the factor or factors underlying the development of cerebral palsy,” said Alexander H. Hoon Jr., M.D., director of the Phelps Center for Cerebral Palsy and Neurodevelopmental Medicine at the Kennedy Krieger Institute in Baltimore.

Cerebral palsy falls into broad etiologic groups: disorders of early brain formation, injury associated with prematurity (periventricular leukomalacia), neonatal encephalopathies, and a heterogeneous group of postnatal disorders. Approximately 30% of cerebral palsy cases are associated with brain malformations, 40% with prematurity, 20% with neonatal encephalopathies, and 10% with postnatal causes—with some regional epidemiologic variability.

Conventional MR imaging and diffusion tensor imaging (DTI) can be used together to establish an etiology and to refine the classification of cerebral palsy. “The importance of establishing an etiology is to use this information to refine therapy, and improve understanding of prognosis and recurrence risk,” said Dr. Hoon. MRI established the diagnosis of periventricular leukomalacia in the child evaluated for spastic quadriplegic cerebral palsy. The DTI images—acquired under a research protocol to refine understanding of pathogenesis and classification—revealed abnormalities in both motor and sensory pathways.

Significant delays in the acquisition of motor skills make clinicians suspect cerebral palsy. For a child with severe cerebral palsy, the disease is usually evident within the first 6–12 months of life; and for a moderately affected child by 1–2 years of age, said Dr. Hoon. For a mildly affected child, clinicians typically wait as long as possible to see if the child develops independent ambulation.

Any child with cerebral palsy should be imaged, he said. Once the diagnosis of cerebral palsy is established, conventional MRI is part of the routine work-up to classify children with cerebral palsy more precisely than by clinical exam. By pinpointing the cause, clinicians can make certain inferences about recurrence risk, and to some extent prognosis, said Dr. Hoon.

MRI also can be useful for children in a gray zone—for whom it's uncertain whether they will develop cerebral palsy. If the MRI appears normal, parents can be reassured, with the caveat from the neurologist that ongoing follow-up is important. It's less clear whether to image children with milder delays but who appear clinically to have a good prognosis.

On MRI, clinicians look for evidence associated with brain malformation, white matter disorder associated with prematurity, injury that occurred in a term infant, or postnatal causes including genetic or metabolic disease. Up to 70%–90% of children with cerebral palsy will have an abnormal MRI. “It's a very helpful diagnostic test,” said Dr. Hoon. For example, cerebral palsy with a normal MRI would suggest other possible causes, including a treatable disorder called dopa responsive dystonia.

DTI reveals abnormalities in white matter tracts by using the diffusion of water along the longitudinal direction of the axons in the tracts. Within white matter, water moves parallel to tracts. Conventional MRI can distinguish white from gray matter but can provide very little detail about the white matter; MRI cannot reveal or quantify specific fiber tract directions.

DTI relies on the principle that water diffusion—or brownian motion—is affected by the properties of the medium in which it occurs. Diffusion within biologic tissues reflects tissue structure and architecture at the microscopic level. DTI allows researchers to look at brain structures that were previously not visible in vivo, he said.

At the Kennedy Krieger Institute, DTI is used in research to evaluate 26 brain white matter tracts in much greater detail to look for abnormalities—small size or absence. Visualizing individual tracts of white matter is only part of the problem. At the moment, researchers don't know exactly what normal tracts look like nor do they know how function correlates with specific tracts.

Dr. Hoon and his colleagues are currently studying the white matter tracts of 30 children born prematurely at various gestational ages, with the goal of correlating tract abnormalities with clinical measures of the child's motor and sensory function. “We're at the very beginning of this process,” said Dr. Hoon.

Once function can be correlated with specific tracts, researchers would then be able to use DTI to establish specific therapies for abnormalities associated with each tract. While DTI is still largely a research tool for cerebral palsy, many MRI scanners have the capacity to perform DT scans.

MR and DT imaging do not pose any risk to children, but there is some risk associated with anesthesia. Young children are typically sedated with chloral hydrate or intravenous sedation to minimize movement in the MR machine and generally do well. In older children with more significant movement, anesthesia may be necessary, which poses some risk, said Dr. Hoon.

Shown are axial MRIs of children with, left to right, holoprosencephaly (brain malformation), schizencephaly (brain malformation), periventricular leukomalacia (prematurity), and hypoxic-ischemic encephalopathy (neonatal encephalopathy).

Axial diffusion tensor images of the same children as above, in the same order as above, reveal white matter tracts oriented in the plane of the image (shown in blue), up and down (shown in green), and left to right (shown in red). Photos courtesy Dr. Susumu Mori and Dr. Lidia Nagae-Poetscher

WASHINGTON – Plasma levels of β-amyloid may be low in elderly patients at risk for mild cognitive impairment or even Alzheimer's disease in the near term, according to research presented at an international conference sponsored by the Alzheimer's Association.

β-Amyloid is secreted as a 40-amino acid species (Aβ40) and a 42-amino acid species (Aβ42), both of which are found in the blood and cerebrospinal fluid (CSF). While Aβ40 is the most prevalent species, Aβ42 forms the plaques that are one of the pathological hallmarks of Alzheimer's disease (AD).

“Our results in this study indicate that the ratio of these two proteins [Aβ42:Aβ40] is a good biomarker for identifying those normal elderly subjects, who will develop Alzheimer's disease and mild cognitive impairment in the next 3–5 years,” said Neill Graff-Radford, M.D., a professor of neurology at the Mayo Clinic in Jacksonville, Fla.

The researchers followed 565 cognitively normal individuals (median age 78 years; 62% female) yearly using the Mattis Dementia Rating Scale (DRS). Patients were followed for 2–12 years (median 3.7 years) after baseline plasma Aβ42 and Aβ40 levels were measured.

Over the course of the study, 54 individuals converted to AD or amnestic mild cognitive impairment (MCI), as diagnosed using the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Association and Mayo criteria.

The researchers compared baseline Aβ42:Aβ40 ratios in subjects who developed either AD or MCI with those who did not, after adjusting for age and apoE genotype–two risk factors for AD. They found that subjects with Aβ42:Aβ40 ratios in the lowest quartile had three times the risk of developing MCI or AD, compared with those in the highest quartile.

Subjects with the lowest ratios of Aβ42:Aβ40 also were significantly more likely to show declined on DRS, even after adjustment for age and apolipoprotein E genotype.

Those with ratios in the lowest quartile developed AD or MCI earlier than those in the other groups, too. Participants in the lowest quartile started developing AD or MCI around 2 years' follow-up, while those with ratios in the next lowest quartile began around 4 years, and those in the upper half began at 6–8 years.

In those older than 80 years and with ratios in the lower half, 20% developed AD in 5 years, compared with 5% of those in the upper half.

“We have pretty convincing evidence and many of us believe that Aβ42 is a very important therapeutic target,” Dr. Graff-Radford said. High plasma levels of Aβ42 have been associated with the early-onset genetic form of AD, Down syndrome, the aging process, and with being a relative of someone with AD. However, low Aβ42 levels have been found in the cerebrospinal fluid of patients with MCI or AD. Data from animal models suggest that low plasma and CSF levels may be a consequence of Aβ42 deposition in the brain.

A biomarker for the disease could spur research into drugs and other preventive measures.

“To develop preventive therapies for Alzheimer's … it's essential to have biomarkers related to Alzheimer's that identify the people at risk before they get the disease–kind of like a cholesterol test,” Dr. Graff-Radford said.

WASHINGTON – Plasma levels of β-amyloid may be low in elderly patients at risk for mild cognitive impairment or even Alzheimer's disease in the near term, according to research presented at an international conference sponsored by the Alzheimer's Association.

β-Amyloid is secreted as a 40-amino acid species (Aβ40) and a 42-amino acid species (Aβ42), both of which are found in the blood and cerebrospinal fluid (CSF). While Aβ40 is the most prevalent species, Aβ42 forms the plaques that are one of the pathological hallmarks of Alzheimer's disease (AD).

“Our results in this study indicate that the ratio of these two proteins [Aβ42:Aβ40] is a good biomarker for identifying those normal elderly subjects, who will develop Alzheimer's disease and mild cognitive impairment in the next 3–5 years,” said Neill Graff-Radford, M.D., a professor of neurology at the Mayo Clinic in Jacksonville, Fla.

The researchers followed 565 cognitively normal individuals (median age 78 years; 62% female) yearly using the Mattis Dementia Rating Scale (DRS). Patients were followed for 2–12 years (median 3.7 years) after baseline plasma Aβ42 and Aβ40 levels were measured.

Over the course of the study, 54 individuals converted to AD or amnestic mild cognitive impairment (MCI), as diagnosed using the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Association and Mayo criteria.

The researchers compared baseline Aβ42:Aβ40 ratios in subjects who developed either AD or MCI with those who did not, after adjusting for age and apoE genotype–two risk factors for AD. They found that subjects with Aβ42:Aβ40 ratios in the lowest quartile had three times the risk of developing MCI or AD, compared with those in the highest quartile.

Subjects with the lowest ratios of Aβ42:Aβ40 also were significantly more likely to show declined on DRS, even after adjustment for age and apolipoprotein E genotype.

Those with ratios in the lowest quartile developed AD or MCI earlier than those in the other groups, too. Participants in the lowest quartile started developing AD or MCI around 2 years' follow-up, while those with ratios in the next lowest quartile began around 4 years, and those in the upper half began at 6–8 years.

In those older than 80 years and with ratios in the lower half, 20% developed AD in 5 years, compared with 5% of those in the upper half.

“We have pretty convincing evidence and many of us believe that Aβ42 is a very important therapeutic target,” Dr. Graff-Radford said. High plasma levels of Aβ42 have been associated with the early-onset genetic form of AD, Down syndrome, the aging process, and with being a relative of someone with AD. However, low Aβ42 levels have been found in the cerebrospinal fluid of patients with MCI or AD. Data from animal models suggest that low plasma and CSF levels may be a consequence of Aβ42 deposition in the brain.

A biomarker for the disease could spur research into drugs and other preventive measures.

“To develop preventive therapies for Alzheimer's … it's essential to have biomarkers related to Alzheimer's that identify the people at risk before they get the disease–kind of like a cholesterol test,” Dr. Graff-Radford said.

WASHINGTON – Plasma levels of β-amyloid may be low in elderly patients at risk for mild cognitive impairment or even Alzheimer's disease in the near term, according to research presented at an international conference sponsored by the Alzheimer's Association.

β-Amyloid is secreted as a 40-amino acid species (Aβ40) and a 42-amino acid species (Aβ42), both of which are found in the blood and cerebrospinal fluid (CSF). While Aβ40 is the most prevalent species, Aβ42 forms the plaques that are one of the pathological hallmarks of Alzheimer's disease (AD).

“Our results in this study indicate that the ratio of these two proteins [Aβ42:Aβ40] is a good biomarker for identifying those normal elderly subjects, who will develop Alzheimer's disease and mild cognitive impairment in the next 3–5 years,” said Neill Graff-Radford, M.D., a professor of neurology at the Mayo Clinic in Jacksonville, Fla.

The researchers followed 565 cognitively normal individuals (median age 78 years; 62% female) yearly using the Mattis Dementia Rating Scale (DRS). Patients were followed for 2–12 years (median 3.7 years) after baseline plasma Aβ42 and Aβ40 levels were measured.

Over the course of the study, 54 individuals converted to AD or amnestic mild cognitive impairment (MCI), as diagnosed using the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Association and Mayo criteria.

The researchers compared baseline Aβ42:Aβ40 ratios in subjects who developed either AD or MCI with those who did not, after adjusting for age and apoE genotype–two risk factors for AD. They found that subjects with Aβ42:Aβ40 ratios in the lowest quartile had three times the risk of developing MCI or AD, compared with those in the highest quartile.

Subjects with the lowest ratios of Aβ42:Aβ40 also were significantly more likely to show declined on DRS, even after adjustment for age and apolipoprotein E genotype.

Those with ratios in the lowest quartile developed AD or MCI earlier than those in the other groups, too. Participants in the lowest quartile started developing AD or MCI around 2 years' follow-up, while those with ratios in the next lowest quartile began around 4 years, and those in the upper half began at 6–8 years.

In those older than 80 years and with ratios in the lower half, 20% developed AD in 5 years, compared with 5% of those in the upper half.

“We have pretty convincing evidence and many of us believe that Aβ42 is a very important therapeutic target,” Dr. Graff-Radford said. High plasma levels of Aβ42 have been associated with the early-onset genetic form of AD, Down syndrome, the aging process, and with being a relative of someone with AD. However, low Aβ42 levels have been found in the cerebrospinal fluid of patients with MCI or AD. Data from animal models suggest that low plasma and CSF levels may be a consequence of Aβ42 deposition in the brain.

A biomarker for the disease could spur research into drugs and other preventive measures.

“To develop preventive therapies for Alzheimer's … it's essential to have biomarkers related to Alzheimer's that identify the people at risk before they get the disease–kind of like a cholesterol test,” Dr. Graff-Radford said.

WASHINGTON – Hippocampal metabolic reductions seen on PET scans in people with no clinical signs of cognitive impairment may be able to predict who will go on to develop Alzheimer's disease and mild cognitive impairment, according to data presented at an international conference sponsored by the Alzheimer's Association.

Pending further investigation, the technique holds the potential to fast-forward the search for preventive measures–such as new medications–that could hold the disease at bay before it becomes clinically evident.

In a study of 53 people that spanned 24 years, those who eventually progressed from normal cognition at baseline to develop Alzheimer's disease (AD) showed 23% less hippocampal glucose metabolism on baseline fluorodeoxyglucose (FDG) PET scans, compared with a cognitively stable control group. Those who progressed from normal cognition to develop mild cognitive impairment (MCI) showed 11% less hippocampal glucose metabolism, compared with the control group, said Lisa Mosconi, Ph.D., of New York University.

Reduced hippocampal metabolism at baseline predicted progression to AD with 83% sensitivity and 86% specificity–a total accuracy of 85%. Progression to MCI was predicted with 74% sensitivity and 68% specificity–a total accuracy of 71%.

“These numbers are interesting when you consider that the signs of Alzheimer's disease were observed an average of 9 years after baseline, and the signs of MCI were seen 11 years after baseline,” said Dr. Mosconi.

Dr. Mosconi and her colleagues followed 53 normal elderly volunteers for 10–24 years. Participants were at least 50 years old at baseline, had at least 12 years of education, and scored at least 28 on the Mini-Mental State Examination (MMSE) and no greater than 2 on the Global Deterioration Scale.

Every 2 years, the volunteers underwent complete clinical, neuropsychologic evaluations. Throughout the study, all participants also underwent at least two PET scans–30 underwent three scans–at least 3 years apart. All images were acquired with the same scanner.

Over the course of the study, 28 participants remained cognitively normal, 19 eventually developed MCI, and 6 developed AD.

Diagnosis of MCI and AD was made by standard neuropsychologic evaluation.

The three groups (stable normal, normal to MCI, and normal to AD) were similar in terms of gender, education, and MMSE scores. However, the stable normal group was several years younger on average, so the researchers corrected the data for age.

The participants who eventually developed AD lost an average of 4% of their hippocampal glucose metabolism capacity per year, those who developed MCI lost 2%, and the control group lost 1%. The difference between those with AD and the control group was statistically significant, but the difference between those with MCI and the control group was not.

The diagnoses of two of the patients who progressed from normal cognition to AD were confirmed by postmortem examination–the most definitive means of diagnosing the disorder. At this examination, hippocampal and cortical volume reductions were observed that were consistent with AD pathology. At baseline, these two patients had 35% and 15% reduced hippocampal metabolism, respectively, at baseline, compared with the control group.

The PET scans were analyzed using HipMask, a software program developed at the university. To develop this program, the researchers drew hippocampal regions of interest on MRI scans of some study patients (ranging in cognition from normal to AD). The MRI scans (and regions of interest) for each patient were then spatially normalized to the shape of an anatomical brain reference image, which is a custom-made template. The resulting images were then overlaid to produce an image containing only areas of the hippocampus where all of the images overlapped–the HipMask.

“The HipMask is a hippocampal masking image that includes only those portions of the hippocampus where the overlap of the subjects is maximized after size normalization procedures,” said Dr. Mosconi. The HipMask was verified against individual MRI scans. On average, 96% of the HipMask represented true hippocampal tissue.

The HipMask was then applied to PET scans–performed within 3 months of the MRIs–to derive estimates of the hippocampal glucose metabolism–a measure of brain activity.

The results also were validated against the standard region-of-interest technique. There was very good correspondence between the HipMask results and the standard technique in all clinical groups, said Dr. Mosconi.

WASHINGTON – Hippocampal metabolic reductions seen on PET scans in people with no clinical signs of cognitive impairment may be able to predict who will go on to develop Alzheimer's disease and mild cognitive impairment, according to data presented at an international conference sponsored by the Alzheimer's Association.

Pending further investigation, the technique holds the potential to fast-forward the search for preventive measures–such as new medications–that could hold the disease at bay before it becomes clinically evident.

In a study of 53 people that spanned 24 years, those who eventually progressed from normal cognition at baseline to develop Alzheimer's disease (AD) showed 23% less hippocampal glucose metabolism on baseline fluorodeoxyglucose (FDG) PET scans, compared with a cognitively stable control group. Those who progressed from normal cognition to develop mild cognitive impairment (MCI) showed 11% less hippocampal glucose metabolism, compared with the control group, said Lisa Mosconi, Ph.D., of New York University.

Reduced hippocampal metabolism at baseline predicted progression to AD with 83% sensitivity and 86% specificity–a total accuracy of 85%. Progression to MCI was predicted with 74% sensitivity and 68% specificity–a total accuracy of 71%.

“These numbers are interesting when you consider that the signs of Alzheimer's disease were observed an average of 9 years after baseline, and the signs of MCI were seen 11 years after baseline,” said Dr. Mosconi.

Dr. Mosconi and her colleagues followed 53 normal elderly volunteers for 10–24 years. Participants were at least 50 years old at baseline, had at least 12 years of education, and scored at least 28 on the Mini-Mental State Examination (MMSE) and no greater than 2 on the Global Deterioration Scale.

Every 2 years, the volunteers underwent complete clinical, neuropsychologic evaluations. Throughout the study, all participants also underwent at least two PET scans–30 underwent three scans–at least 3 years apart. All images were acquired with the same scanner.

Over the course of the study, 28 participants remained cognitively normal, 19 eventually developed MCI, and 6 developed AD.

Diagnosis of MCI and AD was made by standard neuropsychologic evaluation.

The three groups (stable normal, normal to MCI, and normal to AD) were similar in terms of gender, education, and MMSE scores. However, the stable normal group was several years younger on average, so the researchers corrected the data for age.

The participants who eventually developed AD lost an average of 4% of their hippocampal glucose metabolism capacity per year, those who developed MCI lost 2%, and the control group lost 1%. The difference between those with AD and the control group was statistically significant, but the difference between those with MCI and the control group was not.

The diagnoses of two of the patients who progressed from normal cognition to AD were confirmed by postmortem examination–the most definitive means of diagnosing the disorder. At this examination, hippocampal and cortical volume reductions were observed that were consistent with AD pathology. At baseline, these two patients had 35% and 15% reduced hippocampal metabolism, respectively, at baseline, compared with the control group.

The PET scans were analyzed using HipMask, a software program developed at the university. To develop this program, the researchers drew hippocampal regions of interest on MRI scans of some study patients (ranging in cognition from normal to AD). The MRI scans (and regions of interest) for each patient were then spatially normalized to the shape of an anatomical brain reference image, which is a custom-made template. The resulting images were then overlaid to produce an image containing only areas of the hippocampus where all of the images overlapped–the HipMask.

“The HipMask is a hippocampal masking image that includes only those portions of the hippocampus where the overlap of the subjects is maximized after size normalization procedures,” said Dr. Mosconi. The HipMask was verified against individual MRI scans. On average, 96% of the HipMask represented true hippocampal tissue.

The HipMask was then applied to PET scans–performed within 3 months of the MRIs–to derive estimates of the hippocampal glucose metabolism–a measure of brain activity.

The results also were validated against the standard region-of-interest technique. There was very good correspondence between the HipMask results and the standard technique in all clinical groups, said Dr. Mosconi.

WASHINGTON – Hippocampal metabolic reductions seen on PET scans in people with no clinical signs of cognitive impairment may be able to predict who will go on to develop Alzheimer's disease and mild cognitive impairment, according to data presented at an international conference sponsored by the Alzheimer's Association.

Pending further investigation, the technique holds the potential to fast-forward the search for preventive measures–such as new medications–that could hold the disease at bay before it becomes clinically evident.

In a study of 53 people that spanned 24 years, those who eventually progressed from normal cognition at baseline to develop Alzheimer's disease (AD) showed 23% less hippocampal glucose metabolism on baseline fluorodeoxyglucose (FDG) PET scans, compared with a cognitively stable control group. Those who progressed from normal cognition to develop mild cognitive impairment (MCI) showed 11% less hippocampal glucose metabolism, compared with the control group, said Lisa Mosconi, Ph.D., of New York University.

Reduced hippocampal metabolism at baseline predicted progression to AD with 83% sensitivity and 86% specificity–a total accuracy of 85%. Progression to MCI was predicted with 74% sensitivity and 68% specificity–a total accuracy of 71%.

“These numbers are interesting when you consider that the signs of Alzheimer's disease were observed an average of 9 years after baseline, and the signs of MCI were seen 11 years after baseline,” said Dr. Mosconi.

Dr. Mosconi and her colleagues followed 53 normal elderly volunteers for 10–24 years. Participants were at least 50 years old at baseline, had at least 12 years of education, and scored at least 28 on the Mini-Mental State Examination (MMSE) and no greater than 2 on the Global Deterioration Scale.

Every 2 years, the volunteers underwent complete clinical, neuropsychologic evaluations. Throughout the study, all participants also underwent at least two PET scans–30 underwent three scans–at least 3 years apart. All images were acquired with the same scanner.

Over the course of the study, 28 participants remained cognitively normal, 19 eventually developed MCI, and 6 developed AD.

Diagnosis of MCI and AD was made by standard neuropsychologic evaluation.

The three groups (stable normal, normal to MCI, and normal to AD) were similar in terms of gender, education, and MMSE scores. However, the stable normal group was several years younger on average, so the researchers corrected the data for age.

The participants who eventually developed AD lost an average of 4% of their hippocampal glucose metabolism capacity per year, those who developed MCI lost 2%, and the control group lost 1%. The difference between those with AD and the control group was statistically significant, but the difference between those with MCI and the control group was not.

The diagnoses of two of the patients who progressed from normal cognition to AD were confirmed by postmortem examination–the most definitive means of diagnosing the disorder. At this examination, hippocampal and cortical volume reductions were observed that were consistent with AD pathology. At baseline, these two patients had 35% and 15% reduced hippocampal metabolism, respectively, at baseline, compared with the control group.

The PET scans were analyzed using HipMask, a software program developed at the university. To develop this program, the researchers drew hippocampal regions of interest on MRI scans of some study patients (ranging in cognition from normal to AD). The MRI scans (and regions of interest) for each patient were then spatially normalized to the shape of an anatomical brain reference image, which is a custom-made template. The resulting images were then overlaid to produce an image containing only areas of the hippocampus where all of the images overlapped–the HipMask.

“The HipMask is a hippocampal masking image that includes only those portions of the hippocampus where the overlap of the subjects is maximized after size normalization procedures,” said Dr. Mosconi. The HipMask was verified against individual MRI scans. On average, 96% of the HipMask represented true hippocampal tissue.

The HipMask was then applied to PET scans–performed within 3 months of the MRIs–to derive estimates of the hippocampal glucose metabolism–a measure of brain activity.

The results also were validated against the standard region-of-interest technique. There was very good correspondence between the HipMask results and the standard technique in all clinical groups, said Dr. Mosconi.

ASHEVILLE, N.C. — Though very rare, severe neurologic complications can occur as a result of spinal and epidural blocks for labor and delivery, and keeping an eye out for early symptoms can result in better outcomes, according to one expert.

Spinal hematoma, cauda equina syndrome, bacterial meningitis, and epidural abscess appear to be the most common severe neurologic complications, based on a study of 1,260,000 spinal blocks and 450,000 epidural blocks administered in Sweden between 1990 and 1999, said David C. Mayer, M.D., professor of anesthesiology at the University of North Carolina in Chapel Hill.

Complications occurred more often after placement of epidurals than spinal blocks. The study included 200,000 epidurals for pain relief during labor and 55,000 spinal blocks and epidurals for cesarean sections (Anesthesiology 2004;101:950–9).

“Spinal hematoma has a uniformly bad outcome,” Dr. Mayer said at the Southern Obstetric and Gynecologic seminar. In the study, 27 of the 33 spinal hematoma cases resulted in permanent neurologic damage.

Spinal or epidural hematoma is primarily associated with catheter technique. An indwelling catheter in the epidural space almost always is associated with epidural hematoma. Several other factors can come into play, including spine pathology, difficulty in performing the block, and altered coagulation.

With spine pathology, there may be an abnormal nerve route that increases the likelihood of hitting a blood vessel. Difficult blocks involve multiple sticks and increase the risk of hitting a blood vessel. Altered coagulation combined with catheter insertion or removal can lead to hematoma. “Removing an epidural catheter can be as traumatic as placing it,” Dr. Mayer said.

The key problem associated with epidural hematoma is the diagnosis. Back pain was considered the classic symptom of epidural hematoma, but motor block that does not resolve is now considered a better indicator. Consult an anesthesiologist and neurosurgeon right away if a patient has motor block that persists, is out of proportion for the pain medication given, or develops several days later.

According to a closed claims database that is maintained by the American Society of Anesthesiologists, 90% of neuraxial hematomas result in irreversible damage. Unfortunately, the diagnosis is made well after the onset of symptoms. There's only an 8-hour window between the onset of neurologic changes and laminectomy—the treatment of choice—to avoid any permanent damage. “For many patients, by the time they're evaluated completely, it's past the period in which anything can be done,” Dr. Mayer said.

Anticoagulation medication is now so common among patients receiving anesthesia that the American Society of Regional Anesthesia and Pain Medicine has developed a consensus statement on the use of regional anesthesia in anticoagulated patients (Reg. Anesth. Pain Med. 2003;28:172–97).

According to this guideline, there is no increased risk of hematoma when unfractionated heparin is used for subcutaneous prophylaxis. If the patient has been on this therapy for more than 4 days at the time of epidural placement, a platelet count is needed to rule out heparin-induced thrombocytopenia.

Low molecular weight heparins (LMWHs) are a different matter. LMWHs “have really changed how we give regional anesthesia in the anticoagulated patients,” said Dr. Mayer. If patients are on an LMWH before the epidural is placed, assume that the patient has altered coagulation. Delay needle placement by at least 10–12 hours after giving a dose of LMWH. However, in patients receiving higher doses—for example, 1 mg/kg enoxaparin every 12 hours—delay the epidural for at least 24 hours. “These patients have very abnormal coagulation,” Dr. Mayer said.

Cauda equina syndrome occurred nearly as often as spinal hematoma in the Swedish study but had worse outcomes, with all 32 cases resulting in permanent neurologic damage.

Cauda equina syndrome is characterized by lower extremity weakness or paralysis, bowel or bladder sphincter dysfunction, and saddle anesthesia.

The onset of symptoms can range from a couple of days to a couple of weeks. “It's a very insidious onset. … Once you get these findings, there's actually nothing that can be done, other than rehabilitation,” said Dr. Mayer, who is also a professor of obstetrics and gynecology at the university.

Cauda equina syndrome can be caused by massive disk herniation and compression of nerves. There have been case reports and small series of cases that implicate the use of hyperbaric lidocaine—potentially because of the preservative used or possibly even because of the lidocaine itself. “This is unclear, but a lot of anesthesiologists are hesitant to use any intrathecal lidocaine because of the risk of cauda equina syndrome,” Dr. Mayer said.

Preexisting spinal stenoses also appear to be associated with this syndrome. Spinal stenoses narrow the space in the spinal canal and impede the flow of the epidural, resulting in increased pressure on the nerves. If the patient is older and has vascular disease, ischemia can lead to cauda equina syndrome.

Infectious complications, such as bacterial meningitis and epidural abscess, have the most favorable outcomes, with most patients in the Swedish study making a full recovery.

The best medical outcomes rely on early diagnosis. Fever and backache are clearly the most common symptoms, although neurologic changes may be present as well.

Typically, it takes about 5 days for onset of symptoms. Staphylococcus species are the most commonly identified culprits. And treatment may include antibiotic therapy or even surgery to decompress the spinal cord.

Meningitis is exclusively related to spinal blocks and results from puncture of the dura. Typically, meningitis manifests within 24 hours as headache or neurologic changes.

“Early infectious processes are more likely to be meningitis than epidural abscesses,” Dr. Mayer said. In the Swedish study, streptococci were responsible for most of the meningitis cases.

ASHEVILLE, N.C. — Though very rare, severe neurologic complications can occur as a result of spinal and epidural blocks for labor and delivery, and keeping an eye out for early symptoms can result in better outcomes, according to one expert.

Spinal hematoma, cauda equina syndrome, bacterial meningitis, and epidural abscess appear to be the most common severe neurologic complications, based on a study of 1,260,000 spinal blocks and 450,000 epidural blocks administered in Sweden between 1990 and 1999, said David C. Mayer, M.D., professor of anesthesiology at the University of North Carolina in Chapel Hill.

Complications occurred more often after placement of epidurals than spinal blocks. The study included 200,000 epidurals for pain relief during labor and 55,000 spinal blocks and epidurals for cesarean sections (Anesthesiology 2004;101:950–9).

“Spinal hematoma has a uniformly bad outcome,” Dr. Mayer said at the Southern Obstetric and Gynecologic seminar. In the study, 27 of the 33 spinal hematoma cases resulted in permanent neurologic damage.

Spinal or epidural hematoma is primarily associated with catheter technique. An indwelling catheter in the epidural space almost always is associated with epidural hematoma. Several other factors can come into play, including spine pathology, difficulty in performing the block, and altered coagulation.

With spine pathology, there may be an abnormal nerve route that increases the likelihood of hitting a blood vessel. Difficult blocks involve multiple sticks and increase the risk of hitting a blood vessel. Altered coagulation combined with catheter insertion or removal can lead to hematoma. “Removing an epidural catheter can be as traumatic as placing it,” Dr. Mayer said.

The key problem associated with epidural hematoma is the diagnosis. Back pain was considered the classic symptom of epidural hematoma, but motor block that does not resolve is now considered a better indicator. Consult an anesthesiologist and neurosurgeon right away if a patient has motor block that persists, is out of proportion for the pain medication given, or develops several days later.

According to a closed claims database that is maintained by the American Society of Anesthesiologists, 90% of neuraxial hematomas result in irreversible damage. Unfortunately, the diagnosis is made well after the onset of symptoms. There's only an 8-hour window between the onset of neurologic changes and laminectomy—the treatment of choice—to avoid any permanent damage. “For many patients, by the time they're evaluated completely, it's past the period in which anything can be done,” Dr. Mayer said.

Anticoagulation medication is now so common among patients receiving anesthesia that the American Society of Regional Anesthesia and Pain Medicine has developed a consensus statement on the use of regional anesthesia in anticoagulated patients (Reg. Anesth. Pain Med. 2003;28:172–97).

According to this guideline, there is no increased risk of hematoma when unfractionated heparin is used for subcutaneous prophylaxis. If the patient has been on this therapy for more than 4 days at the time of epidural placement, a platelet count is needed to rule out heparin-induced thrombocytopenia.

Low molecular weight heparins (LMWHs) are a different matter. LMWHs “have really changed how we give regional anesthesia in the anticoagulated patients,” said Dr. Mayer. If patients are on an LMWH before the epidural is placed, assume that the patient has altered coagulation. Delay needle placement by at least 10–12 hours after giving a dose of LMWH. However, in patients receiving higher doses—for example, 1 mg/kg enoxaparin every 12 hours—delay the epidural for at least 24 hours. “These patients have very abnormal coagulation,” Dr. Mayer said.

Cauda equina syndrome occurred nearly as often as spinal hematoma in the Swedish study but had worse outcomes, with all 32 cases resulting in permanent neurologic damage.

Cauda equina syndrome is characterized by lower extremity weakness or paralysis, bowel or bladder sphincter dysfunction, and saddle anesthesia.

The onset of symptoms can range from a couple of days to a couple of weeks. “It's a very insidious onset. … Once you get these findings, there's actually nothing that can be done, other than rehabilitation,” said Dr. Mayer, who is also a professor of obstetrics and gynecology at the university.

Cauda equina syndrome can be caused by massive disk herniation and compression of nerves. There have been case reports and small series of cases that implicate the use of hyperbaric lidocaine—potentially because of the preservative used or possibly even because of the lidocaine itself. “This is unclear, but a lot of anesthesiologists are hesitant to use any intrathecal lidocaine because of the risk of cauda equina syndrome,” Dr. Mayer said.

Preexisting spinal stenoses also appear to be associated with this syndrome. Spinal stenoses narrow the space in the spinal canal and impede the flow of the epidural, resulting in increased pressure on the nerves. If the patient is older and has vascular disease, ischemia can lead to cauda equina syndrome.

Infectious complications, such as bacterial meningitis and epidural abscess, have the most favorable outcomes, with most patients in the Swedish study making a full recovery.

The best medical outcomes rely on early diagnosis. Fever and backache are clearly the most common symptoms, although neurologic changes may be present as well.

Typically, it takes about 5 days for onset of symptoms. Staphylococcus species are the most commonly identified culprits. And treatment may include antibiotic therapy or even surgery to decompress the spinal cord.

Meningitis is exclusively related to spinal blocks and results from puncture of the dura. Typically, meningitis manifests within 24 hours as headache or neurologic changes.

“Early infectious processes are more likely to be meningitis than epidural abscesses,” Dr. Mayer said. In the Swedish study, streptococci were responsible for most of the meningitis cases.

ASHEVILLE, N.C. — Though very rare, severe neurologic complications can occur as a result of spinal and epidural blocks for labor and delivery, and keeping an eye out for early symptoms can result in better outcomes, according to one expert.

Spinal hematoma, cauda equina syndrome, bacterial meningitis, and epidural abscess appear to be the most common severe neurologic complications, based on a study of 1,260,000 spinal blocks and 450,000 epidural blocks administered in Sweden between 1990 and 1999, said David C. Mayer, M.D., professor of anesthesiology at the University of North Carolina in Chapel Hill.

Complications occurred more often after placement of epidurals than spinal blocks. The study included 200,000 epidurals for pain relief during labor and 55,000 spinal blocks and epidurals for cesarean sections (Anesthesiology 2004;101:950–9).

“Spinal hematoma has a uniformly bad outcome,” Dr. Mayer said at the Southern Obstetric and Gynecologic seminar. In the study, 27 of the 33 spinal hematoma cases resulted in permanent neurologic damage.

Spinal or epidural hematoma is primarily associated with catheter technique. An indwelling catheter in the epidural space almost always is associated with epidural hematoma. Several other factors can come into play, including spine pathology, difficulty in performing the block, and altered coagulation.

With spine pathology, there may be an abnormal nerve route that increases the likelihood of hitting a blood vessel. Difficult blocks involve multiple sticks and increase the risk of hitting a blood vessel. Altered coagulation combined with catheter insertion or removal can lead to hematoma. “Removing an epidural catheter can be as traumatic as placing it,” Dr. Mayer said.

The key problem associated with epidural hematoma is the diagnosis. Back pain was considered the classic symptom of epidural hematoma, but motor block that does not resolve is now considered a better indicator. Consult an anesthesiologist and neurosurgeon right away if a patient has motor block that persists, is out of proportion for the pain medication given, or develops several days later.

According to a closed claims database that is maintained by the American Society of Anesthesiologists, 90% of neuraxial hematomas result in irreversible damage. Unfortunately, the diagnosis is made well after the onset of symptoms. There's only an 8-hour window between the onset of neurologic changes and laminectomy—the treatment of choice—to avoid any permanent damage. “For many patients, by the time they're evaluated completely, it's past the period in which anything can be done,” Dr. Mayer said.

Anticoagulation medication is now so common among patients receiving anesthesia that the American Society of Regional Anesthesia and Pain Medicine has developed a consensus statement on the use of regional anesthesia in anticoagulated patients (Reg. Anesth. Pain Med. 2003;28:172–97).

According to this guideline, there is no increased risk of hematoma when unfractionated heparin is used for subcutaneous prophylaxis. If the patient has been on this therapy for more than 4 days at the time of epidural placement, a platelet count is needed to rule out heparin-induced thrombocytopenia.

Low molecular weight heparins (LMWHs) are a different matter. LMWHs “have really changed how we give regional anesthesia in the anticoagulated patients,” said Dr. Mayer. If patients are on an LMWH before the epidural is placed, assume that the patient has altered coagulation. Delay needle placement by at least 10–12 hours after giving a dose of LMWH. However, in patients receiving higher doses—for example, 1 mg/kg enoxaparin every 12 hours—delay the epidural for at least 24 hours. “These patients have very abnormal coagulation,” Dr. Mayer said.

Cauda equina syndrome occurred nearly as often as spinal hematoma in the Swedish study but had worse outcomes, with all 32 cases resulting in permanent neurologic damage.

Cauda equina syndrome is characterized by lower extremity weakness or paralysis, bowel or bladder sphincter dysfunction, and saddle anesthesia.

The onset of symptoms can range from a couple of days to a couple of weeks. “It's a very insidious onset. … Once you get these findings, there's actually nothing that can be done, other than rehabilitation,” said Dr. Mayer, who is also a professor of obstetrics and gynecology at the university.

Cauda equina syndrome can be caused by massive disk herniation and compression of nerves. There have been case reports and small series of cases that implicate the use of hyperbaric lidocaine—potentially because of the preservative used or possibly even because of the lidocaine itself. “This is unclear, but a lot of anesthesiologists are hesitant to use any intrathecal lidocaine because of the risk of cauda equina syndrome,” Dr. Mayer said.

Preexisting spinal stenoses also appear to be associated with this syndrome. Spinal stenoses narrow the space in the spinal canal and impede the flow of the epidural, resulting in increased pressure on the nerves. If the patient is older and has vascular disease, ischemia can lead to cauda equina syndrome.

Infectious complications, such as bacterial meningitis and epidural abscess, have the most favorable outcomes, with most patients in the Swedish study making a full recovery.

The best medical outcomes rely on early diagnosis. Fever and backache are clearly the most common symptoms, although neurologic changes may be present as well.

Typically, it takes about 5 days for onset of symptoms. Staphylococcus species are the most commonly identified culprits. And treatment may include antibiotic therapy or even surgery to decompress the spinal cord.

Meningitis is exclusively related to spinal blocks and results from puncture of the dura. Typically, meningitis manifests within 24 hours as headache or neurologic changes.

“Early infectious processes are more likely to be meningitis than epidural abscesses,” Dr. Mayer said. In the Swedish study, streptococci were responsible for most of the meningitis cases.

WASHINGTON — The renal effects of high-protein diets pose a strong risk of harm in patients with chronic kidney disease, Allon Friedman, M.D., said at a meeting sponsored by the National Kidney Foundation.

Chronic kidney disease is often silent, so he recommends obtaining a serum creatinine measurement and a urinary dipstick test for proteinuria in all patients considering a high-protein diet for weight loss.

Those with a glomerular filtration rate of less than 60 mL/min should be advised against a high-protein diet, noted Dr. Friedman of Indiana University in Indianapolis.

Regardless of kidney function, protein intake increases glomerular filtration rate and renal blood flow by as much as 100% from baseline.

Over time, a high-protein diet appears to increase kidney volume and weight.

Studies suggest that high-protein diets increase urinary protein excretion in people with normal and in those with diminished kidney function, Dr. Friedman said.

High-protein diets are intended to induce ketosis by limiting carbohydrate intake. Increased ketone levels lead to increased sodium output, which in turn induces natriuresis, he said.

In the short-term, high protein consumption has been associated with orthostatic hypotension. There is little evidence that high-protein diets maintained for months adversely effect blood pressure, compared with standard low-fat diets.

Animal and human studies have shown that increased protein consumption leads to hyperuricosuria, hypercalciuria, hypocitraturia, and a reduction in urinary pH—all risk factors for the formation of kidney stones.

Healthy patients considering a high-protein diet should be advised about the potentially deleterious effects: chronic glomerular hyperfiltration and hyperemia, increased proteinuria, and an elevated risk for nephrolithiasis, Dr. Friedman said.

It may be helpful, he added, to point out to patients that although short-term studies (3–6 months) have resulted in more weight loss for high-protein diets than for standard diets, long-term studies (up to 1 year) have shown no differences in weight loss between the two groups.

WASHINGTON — The renal effects of high-protein diets pose a strong risk of harm in patients with chronic kidney disease, Allon Friedman, M.D., said at a meeting sponsored by the National Kidney Foundation.

Chronic kidney disease is often silent, so he recommends obtaining a serum creatinine measurement and a urinary dipstick test for proteinuria in all patients considering a high-protein diet for weight loss.

Those with a glomerular filtration rate of less than 60 mL/min should be advised against a high-protein diet, noted Dr. Friedman of Indiana University in Indianapolis.

Regardless of kidney function, protein intake increases glomerular filtration rate and renal blood flow by as much as 100% from baseline.

Over time, a high-protein diet appears to increase kidney volume and weight.

Studies suggest that high-protein diets increase urinary protein excretion in people with normal and in those with diminished kidney function, Dr. Friedman said.

High-protein diets are intended to induce ketosis by limiting carbohydrate intake. Increased ketone levels lead to increased sodium output, which in turn induces natriuresis, he said.

In the short-term, high protein consumption has been associated with orthostatic hypotension. There is little evidence that high-protein diets maintained for months adversely effect blood pressure, compared with standard low-fat diets.

Animal and human studies have shown that increased protein consumption leads to hyperuricosuria, hypercalciuria, hypocitraturia, and a reduction in urinary pH—all risk factors for the formation of kidney stones.

Healthy patients considering a high-protein diet should be advised about the potentially deleterious effects: chronic glomerular hyperfiltration and hyperemia, increased proteinuria, and an elevated risk for nephrolithiasis, Dr. Friedman said.

It may be helpful, he added, to point out to patients that although short-term studies (3–6 months) have resulted in more weight loss for high-protein diets than for standard diets, long-term studies (up to 1 year) have shown no differences in weight loss between the two groups.

WASHINGTON — The renal effects of high-protein diets pose a strong risk of harm in patients with chronic kidney disease, Allon Friedman, M.D., said at a meeting sponsored by the National Kidney Foundation.

Chronic kidney disease is often silent, so he recommends obtaining a serum creatinine measurement and a urinary dipstick test for proteinuria in all patients considering a high-protein diet for weight loss.

Those with a glomerular filtration rate of less than 60 mL/min should be advised against a high-protein diet, noted Dr. Friedman of Indiana University in Indianapolis.

Regardless of kidney function, protein intake increases glomerular filtration rate and renal blood flow by as much as 100% from baseline.

Over time, a high-protein diet appears to increase kidney volume and weight.

Studies suggest that high-protein diets increase urinary protein excretion in people with normal and in those with diminished kidney function, Dr. Friedman said.

High-protein diets are intended to induce ketosis by limiting carbohydrate intake. Increased ketone levels lead to increased sodium output, which in turn induces natriuresis, he said.

In the short-term, high protein consumption has been associated with orthostatic hypotension. There is little evidence that high-protein diets maintained for months adversely effect blood pressure, compared with standard low-fat diets.

Animal and human studies have shown that increased protein consumption leads to hyperuricosuria, hypercalciuria, hypocitraturia, and a reduction in urinary pH—all risk factors for the formation of kidney stones.

Healthy patients considering a high-protein diet should be advised about the potentially deleterious effects: chronic glomerular hyperfiltration and hyperemia, increased proteinuria, and an elevated risk for nephrolithiasis, Dr. Friedman said.

It may be helpful, he added, to point out to patients that although short-term studies (3–6 months) have resulted in more weight loss for high-protein diets than for standard diets, long-term studies (up to 1 year) have shown no differences in weight loss between the two groups.

DESTIN, FLA. — The tender-point criteria commonly used to diagnose fibromyalgia are not useful and in fact may even explain why the disease appears to disproportionately affect women, Daniel Clauw, M.D., said at a rheumatology meeting sponsored by Virginia Commonwealth University.

According to the American College of Rheumatology's 1990 classification criteria, patients must have both widespread pain and tenderness in 11 of 18 tender points to be diagnosed with fibromyalgia.

Yet “tender points merely represent areas of the body where everyone is more tender,” explained Dr. Clauw, the executive director of the Chronic Pain and Fatigue Research Center at the University of Michigan in Ann Arbor.

Fibromyalgia patients and healthy individuals were found to have different thresholds of pain in those tender points. The two groups also had different thresholds of pain in areas not thought to be tender. In addition, the cutoff of 11 out of 18 tender points is arbitrary, he said.

In the past, the disorder was considered a discrete illness with pain and focal areas of tenderness. In more recent years, fibromyalgia has been appreciated as part of a larger continuum, with many somatic symptoms and diffuse tenderness all over the body.

Study findings suggest that the number of tender points correlates better with a patient's general stress than with pain, he said.

Women are 10 times more likely to have achy and tender points, so the higher incidence of fibromyalgia among them may be due to a selection bias created by the criteria, Dr. Clauw noted.

DESTIN, FLA. — The tender-point criteria commonly used to diagnose fibromyalgia are not useful and in fact may even explain why the disease appears to disproportionately affect women, Daniel Clauw, M.D., said at a rheumatology meeting sponsored by Virginia Commonwealth University.

According to the American College of Rheumatology's 1990 classification criteria, patients must have both widespread pain and tenderness in 11 of 18 tender points to be diagnosed with fibromyalgia.

Yet “tender points merely represent areas of the body where everyone is more tender,” explained Dr. Clauw, the executive director of the Chronic Pain and Fatigue Research Center at the University of Michigan in Ann Arbor.

Fibromyalgia patients and healthy individuals were found to have different thresholds of pain in those tender points. The two groups also had different thresholds of pain in areas not thought to be tender. In addition, the cutoff of 11 out of 18 tender points is arbitrary, he said.

In the past, the disorder was considered a discrete illness with pain and focal areas of tenderness. In more recent years, fibromyalgia has been appreciated as part of a larger continuum, with many somatic symptoms and diffuse tenderness all over the body.

Study findings suggest that the number of tender points correlates better with a patient's general stress than with pain, he said.

Women are 10 times more likely to have achy and tender points, so the higher incidence of fibromyalgia among them may be due to a selection bias created by the criteria, Dr. Clauw noted.

DESTIN, FLA. — The tender-point criteria commonly used to diagnose fibromyalgia are not useful and in fact may even explain why the disease appears to disproportionately affect women, Daniel Clauw, M.D., said at a rheumatology meeting sponsored by Virginia Commonwealth University.

According to the American College of Rheumatology's 1990 classification criteria, patients must have both widespread pain and tenderness in 11 of 18 tender points to be diagnosed with fibromyalgia.

Yet “tender points merely represent areas of the body where everyone is more tender,” explained Dr. Clauw, the executive director of the Chronic Pain and Fatigue Research Center at the University of Michigan in Ann Arbor.

Fibromyalgia patients and healthy individuals were found to have different thresholds of pain in those tender points. The two groups also had different thresholds of pain in areas not thought to be tender. In addition, the cutoff of 11 out of 18 tender points is arbitrary, he said.

In the past, the disorder was considered a discrete illness with pain and focal areas of tenderness. In more recent years, fibromyalgia has been appreciated as part of a larger continuum, with many somatic symptoms and diffuse tenderness all over the body.

Study findings suggest that the number of tender points correlates better with a patient's general stress than with pain, he said.

Women are 10 times more likely to have achy and tender points, so the higher incidence of fibromyalgia among them may be due to a selection bias created by the criteria, Dr. Clauw noted.

WASHINGTON — Imaging techniques designed to enable identification of preclinical Alzheimer's disease were showcased in numerous presentations at an international conference sponsored by the Alzheimer's Association.

Preclinical Biochemical Changes

Using magnetic resonance spectroscopy (MRS), researchers in the United Kingdom identified biochemical changes in the posterior cingulate in a group of symptom-free subjects genetically destined to develop Alzheimer's disease (AD).

The researchers imaged seven volunteers with familial AD, who carry presenilin 1 and amyloid precursor protein gene mutations and have an almost 100% chance of developing AD, according to Alison Godbolt, M.B., of the Dementia Research Centre at University College, London. At the time of the study, these individuals had normal memory. Six healthy volunteers without familial AD were also recruited to serve as controls.

MRS provides information about select chemicals in a specific area of the brain that are involved in metabolism. MRS is performed using the same scanners as magnetic resonance imaging (MRI).

The researchers looked at a single voxel along the midline of the posterior cingulate, a region that is known to be involved in AD. They measured the ratio of n-acetylaspartate to creatine and the ratio of myo-inositol to creatine.

Subjects with the genetic mutation had n-acetylaspartate/creatine ratios that were 10% lower and myo-inositol/creatine ratios that were 20% greater than those of the control group. The difference in the myo-inositol/creatine ratios between the two groups did not reach statistical significance. “Interestingly, other researchers have found the same changes in people who already have the disease,” Dr. Godbolt said.

Reduced levels of n-acetylaspartate are thought to be due to nerve cell dysfunction and loss; increased myo-inositol levels are thought to be due to increased inflammation. In addition, the volunteers with the gene mutation who were closest to their predicted age of onset had the most abnormal levels of these two chemicals.

Screening via Hippocampal Size

Reduced hippocampal volume on MRI, combined with the results of the MiniMental State Examination (MMSE), appears to do a better job of identifying patients with mild cognitive impairment (MCI) and AD than MMSE alone, according to a poster presented by Claire K. Sandstrom, a medical student at Duke University in Durham, N.C., and her colleagues.

Several recent studies have shown that individuals with MCI have smaller hippocampal volumes on MRI, compared with healthy controls. This is especially true for those subgroups of individuals with MCI, who later convert to AD. The researchers hypothesized that information about reduced hippocampal volume in patients with MCI, compared with controls, could enhance the diagnostic utility of MMSE scores.

The researchers evaluated 18 volunteers (11 men) with MCI and 17 volunteers (8 men) with normal cognition with the MMSE and MRI. Those with MCI were age 74 years on average and had a mean MMSE score of 27, while the control group was age 70 years on average and had a mean score of 28.

Left and right hippocampal volumes were calculated from MRI and normalized for intracranial area. Left and right hippocampal volumes and MMSE scores were adjusted for age.

Hippocampal atrophy was greater in the volunteers with MCI than in the controls. Left hippocampal volume was significantly smaller than on the right only in people with MCI. The smaller volume of the left hippocampus may represent an inherent, unilateral property of the disease process, according to the authors. Or, the difference in volumes may be a dose effect for the apolipoprotein e4 allele. The smaller left hippocampal volume may also reflect the fact that the MCI classification system used in this study assessed deficits on verbal rather than visual memory tasks.

The researchers developed receiver operating characteristic curves to evaluate the ability of left hippocampal volume, right hippocampal volume, MMSE score, and the combination of left hippocampal volume and MMSE score to accurately identify patients with AD and MCI. After analyzing these curves, the researchers concluded that left hippocampal volume was superior to MMSE alone in identifying patients with AD and MCI.

Hippocampal volume information from MRI could potentially improve the identification of those at greatest risk for the development of AD in a primary care setting.

DTI Reveals Brain Changes in MCI

Researchers have identified changes in the left and right anterior hippocampus and amygdala in patients with MCI and in those with mild cognitive complaints but not in cognitively normal subjects, using diffusion-tensor imaging (DTI).

The researchers imaged 27 individuals with MCI (mean age 74 years), 25 individuals with cognitive complaints (mean age 73 years), and 33 healthy controls (mean age 72 years), according to a poster presented by John D. West of the Brain Imaging Lab at Dartmouth College in Hanover, N.H., and his colleagues.

The participants were from the ongoing Dartmouth Memory and Aging Study. The groups were balanced for age, education, and sex. They also were assessed using the California Verbal Learning Test.

DTI reveals disruptions of the white matter tracts that are not visible on MRI. Within white matter, water moves parallel to tracts. Conventional MRI can distinguish white from gray matter but can provide very little detail about the white matter; MRI cannot observe or quantify specific fiber tract directions.

DTI relies on the principle that water diffusion is affected by the properties of the medium in which it occurs. Diffusion within biologic tissues reflects tissue structure and architecture at the microscopic level.

In particular, the researchers looked at the ability of water to diffuse in different regions of the brain. The greater the diffusion, also known as trace diffusivity, the less white matter structure there is to limit movement—an indication of white matter degeneration.

An area of increased trace diffusivity—relative to the control group—was found in the right posterior cingulate of both the MCI group and the group with lesser cognitive complaints. The participants with MCI also showed increased trace diffusivity in medial temporal regions relative to the control group.

Relative to controls, patients with MCI were more likely to have increased trace diffusivity in the left and right anterior hippocampus and amygdala. Cerebral water diffusion in the group with lesser cognitive complaints was less than in those with MCI and greater than normal controls.

The researchers correlated trace diffusivity with performance They found that decreasing verbal scores on the California Verbal Learning Test correlated with increasing trace diffusivity in the left and right anterior hippocampus and amygdala.

The findings suggest that DTI could be sensitive to preclinical changes in regions of the brain associated with AD.

Previous studies using diffusion-tensor imaging (DTI) have shown increased diffusivity of water in the hippocampus of older adults with MCI, compared with healthy controls. This finding suggests early degenerative changes in the medial temporal region.

AD vs. Lewy Body Dementia on PET

PET imaging shows that patients with Lewy body dementia (LBD) have slightly more β-amyloid in the occipital and sensorimotor cortex than do patients with AD, a finding that may help physicians distinguish the two conditions with similar symptoms, according to a poster presented by Victor L. Villemagne, M.D., of Austin Hospital in Melbourne, Australia.

The researchers took advantage of a relatively new PET tracer—the Pittsburgh Compound B (PIB)—to image β-amyloid in the brain. PIB is a derivative of thiamine that is labeled with radioactive carbon and attaches to β-amyloid deposits in the brain that show up on PET imaging.

The researchers imaged eight patients with AD, seven patients with LBD, and seven age-matched healthy controls using PIB PET and

PIB PET images of the patients with AD showed marked binding in the frontal, parietal, and lateral temporal cortices, as well as the caudate nuclei, suggesting that there were significant β-amyloid deposits there. There was relative sparing of the occipital and sensorimotor cortex and very low uptake in the cerebellar cortex. Patients with LBD appeared similar to those with AD but slightly higher uptake was noted in the occipital and sensorimotor cortex.

The normal controls showed little or no PIB retention in any cortical and subcortical gray matter areas. Areas of PIB binding were inversely correlated with FDG uptake areas—a brain activity measure.

The use of PIB binding patterns can distinguish LBD from AD, said Dr. Villemagne, also of the department of pathology at the University of Melbourne.

LBD is the second most common dementia cause after AD, and it is difficult to distinguish the two disorders. Postmortem studies of LBD have shown that the majority of patients have cortical β-amyloid deposits similar to those in AD patients.

In addition, the researchers have also scanned individuals with Parkinson's disease and frontotemporal dementia using PIB-PET imaging. They found no cortical PIB retention, only white matter retention. α-Synuclein protein is the hallmark of certain neurodegenerative diseases. Tau protein forms the neurofibrillary tangles that are associated with AD.

WASHINGTON — Imaging techniques designed to enable identification of preclinical Alzheimer's disease were showcased in numerous presentations at an international conference sponsored by the Alzheimer's Association.

Preclinical Biochemical Changes

Using magnetic resonance spectroscopy (MRS), researchers in the United Kingdom identified biochemical changes in the posterior cingulate in a group of symptom-free subjects genetically destined to develop Alzheimer's disease (AD).

The researchers imaged seven volunteers with familial AD, who carry presenilin 1 and amyloid precursor protein gene mutations and have an almost 100% chance of developing AD, according to Alison Godbolt, M.B., of the Dementia Research Centre at University College, London. At the time of the study, these individuals had normal memory. Six healthy volunteers without familial AD were also recruited to serve as controls.

MRS provides information about select chemicals in a specific area of the brain that are involved in metabolism. MRS is performed using the same scanners as magnetic resonance imaging (MRI).

The researchers looked at a single voxel along the midline of the posterior cingulate, a region that is known to be involved in AD. They measured the ratio of n-acetylaspartate to creatine and the ratio of myo-inositol to creatine.

Subjects with the genetic mutation had n-acetylaspartate/creatine ratios that were 10% lower and myo-inositol/creatine ratios that were 20% greater than those of the control group. The difference in the myo-inositol/creatine ratios between the two groups did not reach statistical significance. “Interestingly, other researchers have found the same changes in people who already have the disease,” Dr. Godbolt said.

Reduced levels of n-acetylaspartate are thought to be due to nerve cell dysfunction and loss; increased myo-inositol levels are thought to be due to increased inflammation. In addition, the volunteers with the gene mutation who were closest to their predicted age of onset had the most abnormal levels of these two chemicals.

Screening via Hippocampal Size

Reduced hippocampal volume on MRI, combined with the results of the MiniMental State Examination (MMSE), appears to do a better job of identifying patients with mild cognitive impairment (MCI) and AD than MMSE alone, according to a poster presented by Claire K. Sandstrom, a medical student at Duke University in Durham, N.C., and her colleagues.

Several recent studies have shown that individuals with MCI have smaller hippocampal volumes on MRI, compared with healthy controls. This is especially true for those subgroups of individuals with MCI, who later convert to AD. The researchers hypothesized that information about reduced hippocampal volume in patients with MCI, compared with controls, could enhance the diagnostic utility of MMSE scores.

The researchers evaluated 18 volunteers (11 men) with MCI and 17 volunteers (8 men) with normal cognition with the MMSE and MRI. Those with MCI were age 74 years on average and had a mean MMSE score of 27, while the control group was age 70 years on average and had a mean score of 28.

Left and right hippocampal volumes were calculated from MRI and normalized for intracranial area. Left and right hippocampal volumes and MMSE scores were adjusted for age.

Hippocampal atrophy was greater in the volunteers with MCI than in the controls. Left hippocampal volume was significantly smaller than on the right only in people with MCI. The smaller volume of the left hippocampus may represent an inherent, unilateral property of the disease process, according to the authors. Or, the difference in volumes may be a dose effect for the apolipoprotein e4 allele. The smaller left hippocampal volume may also reflect the fact that the MCI classification system used in this study assessed deficits on verbal rather than visual memory tasks.

The researchers developed receiver operating characteristic curves to evaluate the ability of left hippocampal volume, right hippocampal volume, MMSE score, and the combination of left hippocampal volume and MMSE score to accurately identify patients with AD and MCI. After analyzing these curves, the researchers concluded that left hippocampal volume was superior to MMSE alone in identifying patients with AD and MCI.

Hippocampal volume information from MRI could potentially improve the identification of those at greatest risk for the development of AD in a primary care setting.

DTI Reveals Brain Changes in MCI

Researchers have identified changes in the left and right anterior hippocampus and amygdala in patients with MCI and in those with mild cognitive complaints but not in cognitively normal subjects, using diffusion-tensor imaging (DTI).

The researchers imaged 27 individuals with MCI (mean age 74 years), 25 individuals with cognitive complaints (mean age 73 years), and 33 healthy controls (mean age 72 years), according to a poster presented by John D. West of the Brain Imaging Lab at Dartmouth College in Hanover, N.H., and his colleagues.

The participants were from the ongoing Dartmouth Memory and Aging Study. The groups were balanced for age, education, and sex. They also were assessed using the California Verbal Learning Test.

DTI reveals disruptions of the white matter tracts that are not visible on MRI. Within white matter, water moves parallel to tracts. Conventional MRI can distinguish white from gray matter but can provide very little detail about the white matter; MRI cannot observe or quantify specific fiber tract directions.

DTI relies on the principle that water diffusion is affected by the properties of the medium in which it occurs. Diffusion within biologic tissues reflects tissue structure and architecture at the microscopic level.

In particular, the researchers looked at the ability of water to diffuse in different regions of the brain. The greater the diffusion, also known as trace diffusivity, the less white matter structure there is to limit movement—an indication of white matter degeneration.

An area of increased trace diffusivity—relative to the control group—was found in the right posterior cingulate of both the MCI group and the group with lesser cognitive complaints. The participants with MCI also showed increased trace diffusivity in medial temporal regions relative to the control group.

Relative to controls, patients with MCI were more likely to have increased trace diffusivity in the left and right anterior hippocampus and amygdala. Cerebral water diffusion in the group with lesser cognitive complaints was less than in those with MCI and greater than normal controls.

The researchers correlated trace diffusivity with performance They found that decreasing verbal scores on the California Verbal Learning Test correlated with increasing trace diffusivity in the left and right anterior hippocampus and amygdala.

The findings suggest that DTI could be sensitive to preclinical changes in regions of the brain associated with AD.

Previous studies using diffusion-tensor imaging (DTI) have shown increased diffusivity of water in the hippocampus of older adults with MCI, compared with healthy controls. This finding suggests early degenerative changes in the medial temporal region.

AD vs. Lewy Body Dementia on PET

PET imaging shows that patients with Lewy body dementia (LBD) have slightly more β-amyloid in the occipital and sensorimotor cortex than do patients with AD, a finding that may help physicians distinguish the two conditions with similar symptoms, according to a poster presented by Victor L. Villemagne, M.D., of Austin Hospital in Melbourne, Australia.

The researchers took advantage of a relatively new PET tracer—the Pittsburgh Compound B (PIB)—to image β-amyloid in the brain. PIB is a derivative of thiamine that is labeled with radioactive carbon and attaches to β-amyloid deposits in the brain that show up on PET imaging.

The researchers imaged eight patients with AD, seven patients with LBD, and seven age-matched healthy controls using PIB PET and

PIB PET images of the patients with AD showed marked binding in the frontal, parietal, and lateral temporal cortices, as well as the caudate nuclei, suggesting that there were significant β-amyloid deposits there. There was relative sparing of the occipital and sensorimotor cortex and very low uptake in the cerebellar cortex. Patients with LBD appeared similar to those with AD but slightly higher uptake was noted in the occipital and sensorimotor cortex.

The normal controls showed little or no PIB retention in any cortical and subcortical gray matter areas. Areas of PIB binding were inversely correlated with FDG uptake areas—a brain activity measure.

The use of PIB binding patterns can distinguish LBD from AD, said Dr. Villemagne, also of the department of pathology at the University of Melbourne.

LBD is the second most common dementia cause after AD, and it is difficult to distinguish the two disorders. Postmortem studies of LBD have shown that the majority of patients have cortical β-amyloid deposits similar to those in AD patients.

In addition, the researchers have also scanned individuals with Parkinson's disease and frontotemporal dementia using PIB-PET imaging. They found no cortical PIB retention, only white matter retention. α-Synuclein protein is the hallmark of certain neurodegenerative diseases. Tau protein forms the neurofibrillary tangles that are associated with AD.

WASHINGTON — Imaging techniques designed to enable identification of preclinical Alzheimer's disease were showcased in numerous presentations at an international conference sponsored by the Alzheimer's Association.

Preclinical Biochemical Changes

Using magnetic resonance spectroscopy (MRS), researchers in the United Kingdom identified biochemical changes in the posterior cingulate in a group of symptom-free subjects genetically destined to develop Alzheimer's disease (AD).

The researchers imaged seven volunteers with familial AD, who carry presenilin 1 and amyloid precursor protein gene mutations and have an almost 100% chance of developing AD, according to Alison Godbolt, M.B., of the Dementia Research Centre at University College, London. At the time of the study, these individuals had normal memory. Six healthy volunteers without familial AD were also recruited to serve as controls.

MRS provides information about select chemicals in a specific area of the brain that are involved in metabolism. MRS is performed using the same scanners as magnetic resonance imaging (MRI).

The researchers looked at a single voxel along the midline of the posterior cingulate, a region that is known to be involved in AD. They measured the ratio of n-acetylaspartate to creatine and the ratio of myo-inositol to creatine.

Subjects with the genetic mutation had n-acetylaspartate/creatine ratios that were 10% lower and myo-inositol/creatine ratios that were 20% greater than those of the control group. The difference in the myo-inositol/creatine ratios between the two groups did not reach statistical significance. “Interestingly, other researchers have found the same changes in people who already have the disease,” Dr. Godbolt said.

Reduced levels of n-acetylaspartate are thought to be due to nerve cell dysfunction and loss; increased myo-inositol levels are thought to be due to increased inflammation. In addition, the volunteers with the gene mutation who were closest to their predicted age of onset had the most abnormal levels of these two chemicals.

Screening via Hippocampal Size

Reduced hippocampal volume on MRI, combined with the results of the MiniMental State Examination (MMSE), appears to do a better job of identifying patients with mild cognitive impairment (MCI) and AD than MMSE alone, according to a poster presented by Claire K. Sandstrom, a medical student at Duke University in Durham, N.C., and her colleagues.

Several recent studies have shown that individuals with MCI have smaller hippocampal volumes on MRI, compared with healthy controls. This is especially true for those subgroups of individuals with MCI, who later convert to AD. The researchers hypothesized that information about reduced hippocampal volume in patients with MCI, compared with controls, could enhance the diagnostic utility of MMSE scores.

The researchers evaluated 18 volunteers (11 men) with MCI and 17 volunteers (8 men) with normal cognition with the MMSE and MRI. Those with MCI were age 74 years on average and had a mean MMSE score of 27, while the control group was age 70 years on average and had a mean score of 28.

Left and right hippocampal volumes were calculated from MRI and normalized for intracranial area. Left and right hippocampal volumes and MMSE scores were adjusted for age.

Hippocampal atrophy was greater in the volunteers with MCI than in the controls. Left hippocampal volume was significantly smaller than on the right only in people with MCI. The smaller volume of the left hippocampus may represent an inherent, unilateral property of the disease process, according to the authors. Or, the difference in volumes may be a dose effect for the apolipoprotein e4 allele. The smaller left hippocampal volume may also reflect the fact that the MCI classification system used in this study assessed deficits on verbal rather than visual memory tasks.

The researchers developed receiver operating characteristic curves to evaluate the ability of left hippocampal volume, right hippocampal volume, MMSE score, and the combination of left hippocampal volume and MMSE score to accurately identify patients with AD and MCI. After analyzing these curves, the researchers concluded that left hippocampal volume was superior to MMSE alone in identifying patients with AD and MCI.

Hippocampal volume information from MRI could potentially improve the identification of those at greatest risk for the development of AD in a primary care setting.

DTI Reveals Brain Changes in MCI

Researchers have identified changes in the left and right anterior hippocampus and amygdala in patients with MCI and in those with mild cognitive complaints but not in cognitively normal subjects, using diffusion-tensor imaging (DTI).

The researchers imaged 27 individuals with MCI (mean age 74 years), 25 individuals with cognitive complaints (mean age 73 years), and 33 healthy controls (mean age 72 years), according to a poster presented by John D. West of the Brain Imaging Lab at Dartmouth College in Hanover, N.H., and his colleagues.

The participants were from the ongoing Dartmouth Memory and Aging Study. The groups were balanced for age, education, and sex. They also were assessed using the California Verbal Learning Test.

DTI reveals disruptions of the white matter tracts that are not visible on MRI. Within white matter, water moves parallel to tracts. Conventional MRI can distinguish white from gray matter but can provide very little detail about the white matter; MRI cannot observe or quantify specific fiber tract directions.

DTI relies on the principle that water diffusion is affected by the properties of the medium in which it occurs. Diffusion within biologic tissues reflects tissue structure and architecture at the microscopic level.

In particular, the researchers looked at the ability of water to diffuse in different regions of the brain. The greater the diffusion, also known as trace diffusivity, the less white matter structure there is to limit movement—an indication of white matter degeneration.

An area of increased trace diffusivity—relative to the control group—was found in the right posterior cingulate of both the MCI group and the group with lesser cognitive complaints. The participants with MCI also showed increased trace diffusivity in medial temporal regions relative to the control group.

Relative to controls, patients with MCI were more likely to have increased trace diffusivity in the left and right anterior hippocampus and amygdala. Cerebral water diffusion in the group with lesser cognitive complaints was less than in those with MCI and greater than normal controls.

The researchers correlated trace diffusivity with performance They found that decreasing verbal scores on the California Verbal Learning Test correlated with increasing trace diffusivity in the left and right anterior hippocampus and amygdala.

The findings suggest that DTI could be sensitive to preclinical changes in regions of the brain associated with AD.

Previous studies using diffusion-tensor imaging (DTI) have shown increased diffusivity of water in the hippocampus of older adults with MCI, compared with healthy controls. This finding suggests early degenerative changes in the medial temporal region.

AD vs. Lewy Body Dementia on PET

PET imaging shows that patients with Lewy body dementia (LBD) have slightly more β-amyloid in the occipital and sensorimotor cortex than do patients with AD, a finding that may help physicians distinguish the two conditions with similar symptoms, according to a poster presented by Victor L. Villemagne, M.D., of Austin Hospital in Melbourne, Australia.

The researchers took advantage of a relatively new PET tracer—the Pittsburgh Compound B (PIB)—to image β-amyloid in the brain. PIB is a derivative of thiamine that is labeled with radioactive carbon and attaches to β-amyloid deposits in the brain that show up on PET imaging.

The researchers imaged eight patients with AD, seven patients with LBD, and seven age-matched healthy controls using PIB PET and

PIB PET images of the patients with AD showed marked binding in the frontal, parietal, and lateral temporal cortices, as well as the caudate nuclei, suggesting that there were significant β-amyloid deposits there. There was relative sparing of the occipital and sensorimotor cortex and very low uptake in the cerebellar cortex. Patients with LBD appeared similar to those with AD but slightly higher uptake was noted in the occipital and sensorimotor cortex.

The normal controls showed little or no PIB retention in any cortical and subcortical gray matter areas. Areas of PIB binding were inversely correlated with FDG uptake areas—a brain activity measure.

The use of PIB binding patterns can distinguish LBD from AD, said Dr. Villemagne, also of the department of pathology at the University of Melbourne.

LBD is the second most common dementia cause after AD, and it is difficult to distinguish the two disorders. Postmortem studies of LBD have shown that the majority of patients have cortical β-amyloid deposits similar to those in AD patients.

In addition, the researchers have also scanned individuals with Parkinson's disease and frontotemporal dementia using PIB-PET imaging. They found no cortical PIB retention, only white matter retention. α-Synuclein protein is the hallmark of certain neurodegenerative diseases. Tau protein forms the neurofibrillary tangles that are associated with AD.