Michele G. Sullivan

WASHINGTON — Sural nerve biopsy may be indicated in patients with refractory diabetic neuropathy, because they may have neural inflammation that responds to intravenous immunoglobulin, Dr. David S. Younger reported in a poster at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine.

“Diabetes itself is a partially autoimmune process, or leads to the development of immunological changes,” Dr. Younger said in an interview. “Diabetic neuropathy is emerging as a disease mediated by autoimmunity and, therefore, it appears to respond to immunomodulating treatment—especially the neuropathic pain.”

In 1996, Dr. Younger, of New York University Medical Center, and his colleagues at Columbia University in New York, reported CD8-positive T cell infiltration in and around the walls of peripheral nerve microvessels in patients with diabetic neuropathy. They also noted inflammatory intermediate cytokines and activated C5b-9 membrane attack complex (MAC) in the endoneurium in the majority of the patients they studied. The researchers concluded that cell and humoral mediated immunologic mechanisms might be contributing to the pathogenesis of diabetic neuropathy (Muscle Nerve 1996;19:722–7).

At the meeting, Dr. Younger presented a 10-year review of 111 diabetic patients (aged 31–95 years) with neuropathic pain, progressive motor weakness, and disability characterized by distal symmetric polyneuropathy or proximal neuropathy, and 3 patients with mononeuritis multiplex. All underwent sural nerve biopsies to assist in management.

Axonopathy was present in 45 nerves, and myelinopathy in 23; 16 nerves met clinical and pathologic criteria for chronic inflammatory demyelinating polyneuropathy. Twenty-nine nerves showed inflammation in the microvasculature, including perivasculitis (26), microvasculitis (3), and necrotizing arteritis (3).

Twenty-nine patients with microvascular inflammation and/or chronic demyelinating polyneuropathy received immunotherapy with intravenous immunoglobulin in a regimen of 2 g/kg per month for 3–6 months. During follow-up phone interviews, all reported significant improvement in neuropathic pain.

There's little to lose by performing a nerve biopsy on patients whose diabetic neuropathy pain is poorly controlled on medication, Dr. Younger said. “Sural nerve biopsy is relatively safe, and it assists in the selection of patients who might benefit from immunotherapy.”

In this specimen, microvasculitis with lymphocytic T-cell infiltration of peripheral nerve neuropathy is visible.

This photo shows lymphocytic T-cell infiltration in perivasculitis of peripheral nerve microvessels. Photos courtesy Dr. David S. Younger

WASHINGTON — Sural nerve biopsy may be indicated in patients with refractory diabetic neuropathy, because they may have neural inflammation that responds to intravenous immunoglobulin, Dr. David S. Younger reported in a poster at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine.

“Diabetes itself is a partially autoimmune process, or leads to the development of immunological changes,” Dr. Younger said in an interview. “Diabetic neuropathy is emerging as a disease mediated by autoimmunity and, therefore, it appears to respond to immunomodulating treatment—especially the neuropathic pain.”

In 1996, Dr. Younger, of New York University Medical Center, and his colleagues at Columbia University in New York, reported CD8-positive T cell infiltration in and around the walls of peripheral nerve microvessels in patients with diabetic neuropathy. They also noted inflammatory intermediate cytokines and activated C5b-9 membrane attack complex (MAC) in the endoneurium in the majority of the patients they studied. The researchers concluded that cell and humoral mediated immunologic mechanisms might be contributing to the pathogenesis of diabetic neuropathy (Muscle Nerve 1996;19:722–7).

At the meeting, Dr. Younger presented a 10-year review of 111 diabetic patients (aged 31–95 years) with neuropathic pain, progressive motor weakness, and disability characterized by distal symmetric polyneuropathy or proximal neuropathy, and 3 patients with mononeuritis multiplex. All underwent sural nerve biopsies to assist in management.

Axonopathy was present in 45 nerves, and myelinopathy in 23; 16 nerves met clinical and pathologic criteria for chronic inflammatory demyelinating polyneuropathy. Twenty-nine nerves showed inflammation in the microvasculature, including perivasculitis (26), microvasculitis (3), and necrotizing arteritis (3).

Twenty-nine patients with microvascular inflammation and/or chronic demyelinating polyneuropathy received immunotherapy with intravenous immunoglobulin in a regimen of 2 g/kg per month for 3–6 months. During follow-up phone interviews, all reported significant improvement in neuropathic pain.

There's little to lose by performing a nerve biopsy on patients whose diabetic neuropathy pain is poorly controlled on medication, Dr. Younger said. “Sural nerve biopsy is relatively safe, and it assists in the selection of patients who might benefit from immunotherapy.”

In this specimen, microvasculitis with lymphocytic T-cell infiltration of peripheral nerve neuropathy is visible.

This photo shows lymphocytic T-cell infiltration in perivasculitis of peripheral nerve microvessels. Photos courtesy Dr. David S. Younger

WASHINGTON — Sural nerve biopsy may be indicated in patients with refractory diabetic neuropathy, because they may have neural inflammation that responds to intravenous immunoglobulin, Dr. David S. Younger reported in a poster at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine.

“Diabetes itself is a partially autoimmune process, or leads to the development of immunological changes,” Dr. Younger said in an interview. “Diabetic neuropathy is emerging as a disease mediated by autoimmunity and, therefore, it appears to respond to immunomodulating treatment—especially the neuropathic pain.”

In 1996, Dr. Younger, of New York University Medical Center, and his colleagues at Columbia University in New York, reported CD8-positive T cell infiltration in and around the walls of peripheral nerve microvessels in patients with diabetic neuropathy. They also noted inflammatory intermediate cytokines and activated C5b-9 membrane attack complex (MAC) in the endoneurium in the majority of the patients they studied. The researchers concluded that cell and humoral mediated immunologic mechanisms might be contributing to the pathogenesis of diabetic neuropathy (Muscle Nerve 1996;19:722–7).

At the meeting, Dr. Younger presented a 10-year review of 111 diabetic patients (aged 31–95 years) with neuropathic pain, progressive motor weakness, and disability characterized by distal symmetric polyneuropathy or proximal neuropathy, and 3 patients with mononeuritis multiplex. All underwent sural nerve biopsies to assist in management.

Axonopathy was present in 45 nerves, and myelinopathy in 23; 16 nerves met clinical and pathologic criteria for chronic inflammatory demyelinating polyneuropathy. Twenty-nine nerves showed inflammation in the microvasculature, including perivasculitis (26), microvasculitis (3), and necrotizing arteritis (3).

Twenty-nine patients with microvascular inflammation and/or chronic demyelinating polyneuropathy received immunotherapy with intravenous immunoglobulin in a regimen of 2 g/kg per month for 3–6 months. During follow-up phone interviews, all reported significant improvement in neuropathic pain.

There's little to lose by performing a nerve biopsy on patients whose diabetic neuropathy pain is poorly controlled on medication, Dr. Younger said. “Sural nerve biopsy is relatively safe, and it assists in the selection of patients who might benefit from immunotherapy.”

In this specimen, microvasculitis with lymphocytic T-cell infiltration of peripheral nerve neuropathy is visible.

This photo shows lymphocytic T-cell infiltration in perivasculitis of peripheral nerve microvessels. Photos courtesy Dr. David S. Younger

Officials in charge of disclosing financial interests in research agree that disclosure is important, but are confused about how to do so effectively and appropriately, Kevin P. Weinfurt, Ph.D., and his colleagues reported.

Their survey of 42 such officials revealed widely varying opinions on when disclosure should be made, the financial limits that should trigger it, and how much information to share with prospective research subjects, said Dr. Weinfurt of the department of psychiatry at Duke University, Durham, N.C., and his coinvestigators.

“Part of their struggle relates to a lack of clarity regarding the ultimate goals of disclosure,” the researchers wrote. “There is also a lack of systematic data regarding how potential research participants can and will use such information in their decision making” (J. Law Med. Ethics 2006;34:581–91).

The study was based on detailed personal interviews with eight investigators, 23 review board chairs, and 14 conflict-of-interest committee chairs.

The survey was designed to elicit respondents' understandings of how disclosure is done at their institutions and their thoughts on the importance of disclosure, including its risks and benefits to the institution and research subjects.

More than half of those interviewed agreed that disclosure should occur under all circumstances; the rest said disclosure would depend on the degree of the financial relationship.

The most commonly expressed reason for disclosing a financial relationship was to facilitate better-informed decision making for potential subjects.

Other reasons included trust and transparency issues, reducing liability risk, and managing public perception of the institution.

About 80% of respondents said the disclosure should include the name of the funding source. But some said the name of the company or organization wasn't as important as a description—whether it was a nonprofit organization, pharmaceutical company, or government body, for instance.

They also differed on whether the amount of financial interest should be disclosed. Conflict-of-interest committee chairs were most likely to want to share this information (93%), while investigators were least likely (63%).

Those who expressed concern about disclosing the amount felt that level of detail could become cumbersome or confusing in the informed consent statement, and that research subjects might overestimate the impact that particular amounts might actually have on research outcomes.

There was no consensus on what amount should trigger disclosure—the lower limit ranged from $1 to $50,000.

There was general agreement that the nature of the relationship should be disclosed, but no agreement about whether the disclosure should explain the possible impact of those relationships.

Again, concern about overcomplicating the consent statement semed to be at the root of these issues.

Some respondents said the disclosure should include an explanation of how an unscrupulous investigator might alter the research results.

Most respondents dismissed the idea that disclosure could lower enrollment. There was little sympathy among the group for researchers who complained that full disclosure was an invasion of their financial privacy.

There was also concern about how to best highlight disclosure information without overemphasizing its importance or potential risk to a study's integrity.

Some respondents said their consent form highlights the information in bold type, while others place it strategically in the document—at the very beginning, for example.

Many also emphasized that the informed consent process should include a discussion of conflict of interest, not just a read-through of the document.

“Our data suggest that it will be difficult to achieve agreement on the issue of substantial understanding of financial interests,” the researchers concluded. “Before we can resolve what counts as substantial understanding, there must be agreement about what risks are important for potential research participants to understand.”

Officials in charge of disclosing financial interests in research agree that disclosure is important, but are confused about how to do so effectively and appropriately, Kevin P. Weinfurt, Ph.D., and his colleagues reported.

Their survey of 42 such officials revealed widely varying opinions on when disclosure should be made, the financial limits that should trigger it, and how much information to share with prospective research subjects, said Dr. Weinfurt of the department of psychiatry at Duke University, Durham, N.C., and his coinvestigators.

“Part of their struggle relates to a lack of clarity regarding the ultimate goals of disclosure,” the researchers wrote. “There is also a lack of systematic data regarding how potential research participants can and will use such information in their decision making” (J. Law Med. Ethics 2006;34:581–91).

The study was based on detailed personal interviews with eight investigators, 23 review board chairs, and 14 conflict-of-interest committee chairs.

The survey was designed to elicit respondents' understandings of how disclosure is done at their institutions and their thoughts on the importance of disclosure, including its risks and benefits to the institution and research subjects.

More than half of those interviewed agreed that disclosure should occur under all circumstances; the rest said disclosure would depend on the degree of the financial relationship.

The most commonly expressed reason for disclosing a financial relationship was to facilitate better-informed decision making for potential subjects.

Other reasons included trust and transparency issues, reducing liability risk, and managing public perception of the institution.

About 80% of respondents said the disclosure should include the name of the funding source. But some said the name of the company or organization wasn't as important as a description—whether it was a nonprofit organization, pharmaceutical company, or government body, for instance.

They also differed on whether the amount of financial interest should be disclosed. Conflict-of-interest committee chairs were most likely to want to share this information (93%), while investigators were least likely (63%).

Those who expressed concern about disclosing the amount felt that level of detail could become cumbersome or confusing in the informed consent statement, and that research subjects might overestimate the impact that particular amounts might actually have on research outcomes.

There was no consensus on what amount should trigger disclosure—the lower limit ranged from $1 to $50,000.

There was general agreement that the nature of the relationship should be disclosed, but no agreement about whether the disclosure should explain the possible impact of those relationships.

Again, concern about overcomplicating the consent statement semed to be at the root of these issues.

Some respondents said the disclosure should include an explanation of how an unscrupulous investigator might alter the research results.

Most respondents dismissed the idea that disclosure could lower enrollment. There was little sympathy among the group for researchers who complained that full disclosure was an invasion of their financial privacy.

There was also concern about how to best highlight disclosure information without overemphasizing its importance or potential risk to a study's integrity.

Some respondents said their consent form highlights the information in bold type, while others place it strategically in the document—at the very beginning, for example.

Many also emphasized that the informed consent process should include a discussion of conflict of interest, not just a read-through of the document.

“Our data suggest that it will be difficult to achieve agreement on the issue of substantial understanding of financial interests,” the researchers concluded. “Before we can resolve what counts as substantial understanding, there must be agreement about what risks are important for potential research participants to understand.”

Officials in charge of disclosing financial interests in research agree that disclosure is important, but are confused about how to do so effectively and appropriately, Kevin P. Weinfurt, Ph.D., and his colleagues reported.

Their survey of 42 such officials revealed widely varying opinions on when disclosure should be made, the financial limits that should trigger it, and how much information to share with prospective research subjects, said Dr. Weinfurt of the department of psychiatry at Duke University, Durham, N.C., and his coinvestigators.

“Part of their struggle relates to a lack of clarity regarding the ultimate goals of disclosure,” the researchers wrote. “There is also a lack of systematic data regarding how potential research participants can and will use such information in their decision making” (J. Law Med. Ethics 2006;34:581–91).

The study was based on detailed personal interviews with eight investigators, 23 review board chairs, and 14 conflict-of-interest committee chairs.

The survey was designed to elicit respondents' understandings of how disclosure is done at their institutions and their thoughts on the importance of disclosure, including its risks and benefits to the institution and research subjects.

More than half of those interviewed agreed that disclosure should occur under all circumstances; the rest said disclosure would depend on the degree of the financial relationship.

The most commonly expressed reason for disclosing a financial relationship was to facilitate better-informed decision making for potential subjects.

Other reasons included trust and transparency issues, reducing liability risk, and managing public perception of the institution.

About 80% of respondents said the disclosure should include the name of the funding source. But some said the name of the company or organization wasn't as important as a description—whether it was a nonprofit organization, pharmaceutical company, or government body, for instance.

They also differed on whether the amount of financial interest should be disclosed. Conflict-of-interest committee chairs were most likely to want to share this information (93%), while investigators were least likely (63%).

Those who expressed concern about disclosing the amount felt that level of detail could become cumbersome or confusing in the informed consent statement, and that research subjects might overestimate the impact that particular amounts might actually have on research outcomes.

There was no consensus on what amount should trigger disclosure—the lower limit ranged from $1 to $50,000.

There was general agreement that the nature of the relationship should be disclosed, but no agreement about whether the disclosure should explain the possible impact of those relationships.

Again, concern about overcomplicating the consent statement semed to be at the root of these issues.

Some respondents said the disclosure should include an explanation of how an unscrupulous investigator might alter the research results.

Most respondents dismissed the idea that disclosure could lower enrollment. There was little sympathy among the group for researchers who complained that full disclosure was an invasion of their financial privacy.

There was also concern about how to best highlight disclosure information without overemphasizing its importance or potential risk to a study's integrity.

Some respondents said their consent form highlights the information in bold type, while others place it strategically in the document—at the very beginning, for example.

Many also emphasized that the informed consent process should include a discussion of conflict of interest, not just a read-through of the document.

“Our data suggest that it will be difficult to achieve agreement on the issue of substantial understanding of financial interests,” the researchers concluded. “Before we can resolve what counts as substantial understanding, there must be agreement about what risks are important for potential research participants to understand.”

MADRID — Oxcarbazepine appears to significantly decrease hypersexual behavior in patients with Alzheimer's disease, Dr. Joshua Shua-Haim reported in a poster at the 10th International Conference on Alzheimer's Disease and Related Disorders.

All 11 men in the small pilot study showed improvement in the behavior by 2 weeks of treatment, said Dr. Shua-Haim of the Jersey Shore University Medical Center, Neptune, N.J.

All of the patients lived in a special care unit in an assisted living facility. Treatment began with 150 mg oxcarbazepine daily. The dose was titrated by 150 mg/day, given in two divided doses, until the behavior ceased or a maximum of 900 mg/day was reached.

Hypersexual behavior resolved in all 11 patients, at an average dose of 600–750 mg/day, given in two doses. No adverse events were reported, and there were no changes in blood chemistry.

MADRID — Oxcarbazepine appears to significantly decrease hypersexual behavior in patients with Alzheimer's disease, Dr. Joshua Shua-Haim reported in a poster at the 10th International Conference on Alzheimer's Disease and Related Disorders.

All 11 men in the small pilot study showed improvement in the behavior by 2 weeks of treatment, said Dr. Shua-Haim of the Jersey Shore University Medical Center, Neptune, N.J.

All of the patients lived in a special care unit in an assisted living facility. Treatment began with 150 mg oxcarbazepine daily. The dose was titrated by 150 mg/day, given in two divided doses, until the behavior ceased or a maximum of 900 mg/day was reached.

Hypersexual behavior resolved in all 11 patients, at an average dose of 600–750 mg/day, given in two doses. No adverse events were reported, and there were no changes in blood chemistry.

MADRID — Oxcarbazepine appears to significantly decrease hypersexual behavior in patients with Alzheimer's disease, Dr. Joshua Shua-Haim reported in a poster at the 10th International Conference on Alzheimer's Disease and Related Disorders.

All 11 men in the small pilot study showed improvement in the behavior by 2 weeks of treatment, said Dr. Shua-Haim of the Jersey Shore University Medical Center, Neptune, N.J.

All of the patients lived in a special care unit in an assisted living facility. Treatment began with 150 mg oxcarbazepine daily. The dose was titrated by 150 mg/day, given in two divided doses, until the behavior ceased or a maximum of 900 mg/day was reached.

Hypersexual behavior resolved in all 11 patients, at an average dose of 600–750 mg/day, given in two doses. No adverse events were reported, and there were no changes in blood chemistry.

PITTSBURGH — A ketogenic diet seems to work synergistically with a vagus nerve stimulator to reduce refractory seizures by 50%–100% in children who use the methods concurrently, results of a small observational study found.

The concurrent use of the two therapies seems to represent a nonpharmacologic “rational polypharmacy,” Dr. Eric H.W. Kossoff reported in a poster at the annual meeting of the Child Neurology Society.

“Both therapies have multiple mechanisms of action and low side effects, and work well for all kinds of epilepsy, which is what an ideal polytherapy combination would entail,” Dr. Kossoff, a pediatric neurologist at Johns Hopkins Hospital, Baltimore, said in an interview. He had no explanation for the method of action behind apparent synergistic effects of the combined approach, however.

The combined approach also yields rapid results, he said. Of the 30 children studied, 10 had more than a 90% reduction in seizures within the first month of polytherapy.

Dr. Kossoff presented efficacy results in children (median age 10 years) from six epilepsy centers. All 30 of the children had intractable seizures (average 25 per week), and had been on an average of six medications before beginning the combined therapy.

About half of the study patients began with the ketogenic diet and added the vagus nerve stimulator (VNS) later. The other half began with the implant and then added the ketogenic diet.

After 3 months, 29 children were still using the concurrent therapy. Two had become seizure free, 8 had a 90%–99% reduction in seizure frequency, 11 had a reduction of 50%–90%, and 8 had a reduction of less than 50%.

By 6 months, 25 children were still using both methods. At that time, 2 were still seizure free; 5 children had a reduction of 90%–99%, 12 had a reduction of 50%–90%, and 6 had a reduction of less than 50%.

At 1 year, 15 children were still undergoing both therapies, but none were seizure free; five children had a reduction of 90%–99%, seven a reduction of 50%–90%, and three a reduction of less than 50%.

Most of the children who stopped the combination therapy before 1 year dropped the ketogenic diet.

When Dr. Kossoff examined predictive factors, only age and length of VNS off-time were significant. Children who had more than a 90% seizure reduction were significantly younger than were those who had less than a 90% reduction (8.6 years vs. 12 years). Those who had a 5-minute VNS off-time also had significantly better results than did those with shorter off-times.

“Even though both the ketogenic diet and the VNS are effective therapies with low rates of side effects, only about 2% of pediatric epilepsy patients are on both concurrently,” Dr. Kossoff said. “Our recommendation would be to try one or the other first, and if efficacy is good (50% or better) but not superb, consider adding the second,” he said.

PITTSBURGH — A ketogenic diet seems to work synergistically with a vagus nerve stimulator to reduce refractory seizures by 50%–100% in children who use the methods concurrently, results of a small observational study found.

The concurrent use of the two therapies seems to represent a nonpharmacologic “rational polypharmacy,” Dr. Eric H.W. Kossoff reported in a poster at the annual meeting of the Child Neurology Society.

“Both therapies have multiple mechanisms of action and low side effects, and work well for all kinds of epilepsy, which is what an ideal polytherapy combination would entail,” Dr. Kossoff, a pediatric neurologist at Johns Hopkins Hospital, Baltimore, said in an interview. He had no explanation for the method of action behind apparent synergistic effects of the combined approach, however.

The combined approach also yields rapid results, he said. Of the 30 children studied, 10 had more than a 90% reduction in seizures within the first month of polytherapy.

Dr. Kossoff presented efficacy results in children (median age 10 years) from six epilepsy centers. All 30 of the children had intractable seizures (average 25 per week), and had been on an average of six medications before beginning the combined therapy.

About half of the study patients began with the ketogenic diet and added the vagus nerve stimulator (VNS) later. The other half began with the implant and then added the ketogenic diet.

After 3 months, 29 children were still using the concurrent therapy. Two had become seizure free, 8 had a 90%–99% reduction in seizure frequency, 11 had a reduction of 50%–90%, and 8 had a reduction of less than 50%.

By 6 months, 25 children were still using both methods. At that time, 2 were still seizure free; 5 children had a reduction of 90%–99%, 12 had a reduction of 50%–90%, and 6 had a reduction of less than 50%.

At 1 year, 15 children were still undergoing both therapies, but none were seizure free; five children had a reduction of 90%–99%, seven a reduction of 50%–90%, and three a reduction of less than 50%.

Most of the children who stopped the combination therapy before 1 year dropped the ketogenic diet.

When Dr. Kossoff examined predictive factors, only age and length of VNS off-time were significant. Children who had more than a 90% seizure reduction were significantly younger than were those who had less than a 90% reduction (8.6 years vs. 12 years). Those who had a 5-minute VNS off-time also had significantly better results than did those with shorter off-times.

“Even though both the ketogenic diet and the VNS are effective therapies with low rates of side effects, only about 2% of pediatric epilepsy patients are on both concurrently,” Dr. Kossoff said. “Our recommendation would be to try one or the other first, and if efficacy is good (50% or better) but not superb, consider adding the second,” he said.

PITTSBURGH — A ketogenic diet seems to work synergistically with a vagus nerve stimulator to reduce refractory seizures by 50%–100% in children who use the methods concurrently, results of a small observational study found.

The concurrent use of the two therapies seems to represent a nonpharmacologic “rational polypharmacy,” Dr. Eric H.W. Kossoff reported in a poster at the annual meeting of the Child Neurology Society.

“Both therapies have multiple mechanisms of action and low side effects, and work well for all kinds of epilepsy, which is what an ideal polytherapy combination would entail,” Dr. Kossoff, a pediatric neurologist at Johns Hopkins Hospital, Baltimore, said in an interview. He had no explanation for the method of action behind apparent synergistic effects of the combined approach, however.

The combined approach also yields rapid results, he said. Of the 30 children studied, 10 had more than a 90% reduction in seizures within the first month of polytherapy.

Dr. Kossoff presented efficacy results in children (median age 10 years) from six epilepsy centers. All 30 of the children had intractable seizures (average 25 per week), and had been on an average of six medications before beginning the combined therapy.

About half of the study patients began with the ketogenic diet and added the vagus nerve stimulator (VNS) later. The other half began with the implant and then added the ketogenic diet.

After 3 months, 29 children were still using the concurrent therapy. Two had become seizure free, 8 had a 90%–99% reduction in seizure frequency, 11 had a reduction of 50%–90%, and 8 had a reduction of less than 50%.

By 6 months, 25 children were still using both methods. At that time, 2 were still seizure free; 5 children had a reduction of 90%–99%, 12 had a reduction of 50%–90%, and 6 had a reduction of less than 50%.

At 1 year, 15 children were still undergoing both therapies, but none were seizure free; five children had a reduction of 90%–99%, seven a reduction of 50%–90%, and three a reduction of less than 50%.

Most of the children who stopped the combination therapy before 1 year dropped the ketogenic diet.

When Dr. Kossoff examined predictive factors, only age and length of VNS off-time were significant. Children who had more than a 90% seizure reduction were significantly younger than were those who had less than a 90% reduction (8.6 years vs. 12 years). Those who had a 5-minute VNS off-time also had significantly better results than did those with shorter off-times.

“Even though both the ketogenic diet and the VNS are effective therapies with low rates of side effects, only about 2% of pediatric epilepsy patients are on both concurrently,” Dr. Kossoff said. “Our recommendation would be to try one or the other first, and if efficacy is good (50% or better) but not superb, consider adding the second,” he said.

PITTSBURGH — Topiramate appears to be a good choice for preventing pediatric migraine, including basilar migraine, researchers reported at the annual meeting of the Child Neurology Society.

The drug was approved for treatment of adult migraine in 2004, and is used off label for pediatric migraine, said Dr. Marcus Cruz of St. Christopher's Hospital for Children, Philadelphia. “However, the availability of sufficient data to support the effectiveness, tolerability, and adequate dose is scarce and not yet well supported.”

Dr. Cruz retrospectively examined the use of topiramate as a migraine prophylactic in 37 children (mean age 14 years). Most of the group (81%) experienced migraine without aura; 11% had migraine with aura, and the rest of the children had abdominal, ophthalmoplegic, or catamenial migraine.

For 21 patients, topiramate was the first-line prophylactic therapy; for the remainder of the group, it was an add-on drug.

Most of the children (65%) had an excellent or good response to topiramate. Before treatment, the children had an average of 15 headaches per month; after treatment, that number decreased to about 3 per month.

Eight children had side effects, including cognitive effects (four), drowsiness (three), and paresthesias (one). All four patients who experienced cognitive side effects were switched to another medication. There was a direct correlation between dosage and side effects, Dr. Cruz noted. Children taking more than 2 mg/kg per day were significantly more likely to have adverse effects than were children taking less than 2 mg/kg per day.

“We found a significant reduction in headaches beginning at a mean of 1.7 mg/kg per day, with the most effective dose being right at 2 mg/kg per day,” he said. “When the patients started taking more of the drug, they only had a 30% chance of having more improvement in headache control, but they were more likely to get side effects.” He did not see weight loss in this group, perhaps because the doses were smaller than those usually given to patients with seizure disorders.

Topiramate is also effective in preventing basilar-type migraine in children, said Dr. Donald Lewis, of Eastern Virginia Medical School, Norfolk. In a small, parallel-group study, the drug significantly reduced the total number of headache days per month.

Basilar migraine affects up to 19% of children with migraine, and is characterized by episodes of intense dizziness, vertigo, visual disturbances, ataxia, and diplopia, followed by pain. Dr. Lewis' study included 14 children aged 6–18 years who received either 25 mg or 100 mg of topiramate per day.

At baseline, the children had a median of five migraines per month and a median PedMIDAS migraine assessment score of 33, indicating moderate disability. Most of the children reported their pain level as severe or excruciating.

After reaching their target dosage and entering a maintenance phase, 100% of children in the 25-mg/day group and 71% of those in the 100-mg/day group experienced a reduction in all migraine days of at least 50% per month (a median decrease from 4.5 days to 1.5 days), Dr. Lewis said.

The drug also significantly reduced the number of days with basilar migraines in each group from a median of 3 days to a median of 0.6 days per month. Neither dosage had a significant effect on the duration or intensity of any migraines that occurred during treatment, however. The 100-mg dose was not significantly more effective than the 25-mg dose.

Adverse events occurred in five children in each dosage group, with a total of 21 events in the 25-mg group and 14 in the 100-mg group. Of these, only 15 were probably related to the study drug, and none was considered serious. Adverse events included paresthesias, nausea, fatigue, and cognitive symptoms.

The study was supported by a research grant from Ortho-McNeil Neurologics Inc.

PITTSBURGH — Topiramate appears to be a good choice for preventing pediatric migraine, including basilar migraine, researchers reported at the annual meeting of the Child Neurology Society.

The drug was approved for treatment of adult migraine in 2004, and is used off label for pediatric migraine, said Dr. Marcus Cruz of St. Christopher's Hospital for Children, Philadelphia. “However, the availability of sufficient data to support the effectiveness, tolerability, and adequate dose is scarce and not yet well supported.”

Dr. Cruz retrospectively examined the use of topiramate as a migraine prophylactic in 37 children (mean age 14 years). Most of the group (81%) experienced migraine without aura; 11% had migraine with aura, and the rest of the children had abdominal, ophthalmoplegic, or catamenial migraine.

For 21 patients, topiramate was the first-line prophylactic therapy; for the remainder of the group, it was an add-on drug.

Most of the children (65%) had an excellent or good response to topiramate. Before treatment, the children had an average of 15 headaches per month; after treatment, that number decreased to about 3 per month.

Eight children had side effects, including cognitive effects (four), drowsiness (three), and paresthesias (one). All four patients who experienced cognitive side effects were switched to another medication. There was a direct correlation between dosage and side effects, Dr. Cruz noted. Children taking more than 2 mg/kg per day were significantly more likely to have adverse effects than were children taking less than 2 mg/kg per day.

“We found a significant reduction in headaches beginning at a mean of 1.7 mg/kg per day, with the most effective dose being right at 2 mg/kg per day,” he said. “When the patients started taking more of the drug, they only had a 30% chance of having more improvement in headache control, but they were more likely to get side effects.” He did not see weight loss in this group, perhaps because the doses were smaller than those usually given to patients with seizure disorders.

Topiramate is also effective in preventing basilar-type migraine in children, said Dr. Donald Lewis, of Eastern Virginia Medical School, Norfolk. In a small, parallel-group study, the drug significantly reduced the total number of headache days per month.

Basilar migraine affects up to 19% of children with migraine, and is characterized by episodes of intense dizziness, vertigo, visual disturbances, ataxia, and diplopia, followed by pain. Dr. Lewis' study included 14 children aged 6–18 years who received either 25 mg or 100 mg of topiramate per day.

At baseline, the children had a median of five migraines per month and a median PedMIDAS migraine assessment score of 33, indicating moderate disability. Most of the children reported their pain level as severe or excruciating.

After reaching their target dosage and entering a maintenance phase, 100% of children in the 25-mg/day group and 71% of those in the 100-mg/day group experienced a reduction in all migraine days of at least 50% per month (a median decrease from 4.5 days to 1.5 days), Dr. Lewis said.

The drug also significantly reduced the number of days with basilar migraines in each group from a median of 3 days to a median of 0.6 days per month. Neither dosage had a significant effect on the duration or intensity of any migraines that occurred during treatment, however. The 100-mg dose was not significantly more effective than the 25-mg dose.

Adverse events occurred in five children in each dosage group, with a total of 21 events in the 25-mg group and 14 in the 100-mg group. Of these, only 15 were probably related to the study drug, and none was considered serious. Adverse events included paresthesias, nausea, fatigue, and cognitive symptoms.

The study was supported by a research grant from Ortho-McNeil Neurologics Inc.

PITTSBURGH — Topiramate appears to be a good choice for preventing pediatric migraine, including basilar migraine, researchers reported at the annual meeting of the Child Neurology Society.

The drug was approved for treatment of adult migraine in 2004, and is used off label for pediatric migraine, said Dr. Marcus Cruz of St. Christopher's Hospital for Children, Philadelphia. “However, the availability of sufficient data to support the effectiveness, tolerability, and adequate dose is scarce and not yet well supported.”

Dr. Cruz retrospectively examined the use of topiramate as a migraine prophylactic in 37 children (mean age 14 years). Most of the group (81%) experienced migraine without aura; 11% had migraine with aura, and the rest of the children had abdominal, ophthalmoplegic, or catamenial migraine.

For 21 patients, topiramate was the first-line prophylactic therapy; for the remainder of the group, it was an add-on drug.

Most of the children (65%) had an excellent or good response to topiramate. Before treatment, the children had an average of 15 headaches per month; after treatment, that number decreased to about 3 per month.

Eight children had side effects, including cognitive effects (four), drowsiness (three), and paresthesias (one). All four patients who experienced cognitive side effects were switched to another medication. There was a direct correlation between dosage and side effects, Dr. Cruz noted. Children taking more than 2 mg/kg per day were significantly more likely to have adverse effects than were children taking less than 2 mg/kg per day.

“We found a significant reduction in headaches beginning at a mean of 1.7 mg/kg per day, with the most effective dose being right at 2 mg/kg per day,” he said. “When the patients started taking more of the drug, they only had a 30% chance of having more improvement in headache control, but they were more likely to get side effects.” He did not see weight loss in this group, perhaps because the doses were smaller than those usually given to patients with seizure disorders.

Topiramate is also effective in preventing basilar-type migraine in children, said Dr. Donald Lewis, of Eastern Virginia Medical School, Norfolk. In a small, parallel-group study, the drug significantly reduced the total number of headache days per month.

Basilar migraine affects up to 19% of children with migraine, and is characterized by episodes of intense dizziness, vertigo, visual disturbances, ataxia, and diplopia, followed by pain. Dr. Lewis' study included 14 children aged 6–18 years who received either 25 mg or 100 mg of topiramate per day.

At baseline, the children had a median of five migraines per month and a median PedMIDAS migraine assessment score of 33, indicating moderate disability. Most of the children reported their pain level as severe or excruciating.

After reaching their target dosage and entering a maintenance phase, 100% of children in the 25-mg/day group and 71% of those in the 100-mg/day group experienced a reduction in all migraine days of at least 50% per month (a median decrease from 4.5 days to 1.5 days), Dr. Lewis said.

The drug also significantly reduced the number of days with basilar migraines in each group from a median of 3 days to a median of 0.6 days per month. Neither dosage had a significant effect on the duration or intensity of any migraines that occurred during treatment, however. The 100-mg dose was not significantly more effective than the 25-mg dose.

Adverse events occurred in five children in each dosage group, with a total of 21 events in the 25-mg group and 14 in the 100-mg group. Of these, only 15 were probably related to the study drug, and none was considered serious. Adverse events included paresthesias, nausea, fatigue, and cognitive symptoms.

The study was supported by a research grant from Ortho-McNeil Neurologics Inc.

Officials in charge of disclosing financial interests in research agree that disclosure is important, but are confused about how to do so effectively and appropriately, Kevin P. Weinfurt, Ph.D., and his colleagues reported.

Their survey of 42 such officials revealed widely varying opinions on when disclosure should be made, the financial limits that should trigger it, and how much information to share with prospective research subjects, said Dr. Weinfurt of the department of psychiatry at Duke University, Durham, N.C., and his coinvestigators.

“Part of their struggle relates to a lack of clarity regarding the ultimate goals of disclosure,” they wrote. “There is also a lack of systematic data regarding how potential research participants can and will use such information in their decision-making” (J. Law Med. Ethics 2006;34:581–91).

The study was based on personal interviews with eight investigators, 23 review board chairs, and 14 conflict of interest committee chairs. The survey was designed to elicit respondents' understandings of how disclosure is done at their institutions and their thoughts on disclosure, including its risks and benefits to the institution and research subjects.

More than half of those interviewed agreed that disclosure should occur under all circumstances; the rest said disclosure would depend on the degree of the financial relationship. The most commonly expressed reason for disclosing a financial relationship was to facilitate better-informed decision making for potential subjects. Other reasons included trust and transparency issues, reducing liability risk, and managing public perception of the institution.

About 80% of respondents said the disclosure should include the name of the funding source. But some said the name of the company or organization wasn't as important as a description—whether it was a nonprofit organization, pharmaceutical company, or government body, for instance.

They also differed on whether the amount of financial interest should be disclosed. Conflict of interest committee chairs were most likely to want to share this information (93%), while investigators were least likely (63%). Those who expressed concern about disclosing the amount felt that level of detail could become cumbersome or confusing in the informed consent statement, and that research subjects might overestimate the impact that particular amounts might actually have on research outcomes. There was no consensus on what amount should trigger disclosure—the lower limit ranged from $1 to $50,000.

There was general agreement that the nature of the relationship should be disclosed, but no agreement about whether the disclosure should explain the possible impact of those relationships. Again, concern about overcomplicating the consent statement semed to be at the root of these issues. Some respondents said the disclosure should include an explanation of how an unscrupulous investigator might alter the research results.

Most respondents dismissed the idea that disclosure could lower enrollment. There was little sympathy among the group for researchers who complained that full disclosure was an invasion of their financial privacy.

There was also concern about how to best highlight disclosure information without overemphasizing its importance or potential risk to a study's integrity. Some respondents said their consent form highlights the information in bold type, while others place it strategically in the document—at the very beginning, for example. Many also emphasized that the informed consent process should include a discussion of conflict of interest, not just a read-through of the document.

“Our data suggest that it will be difficult to achieve agreement on the issue of substantial understanding of financial interests,” they wrote. There must first be agreement about what risks are important for research participants to understand.

Officials in charge of disclosing financial interests in research agree that disclosure is important, but are confused about how to do so effectively and appropriately, Kevin P. Weinfurt, Ph.D., and his colleagues reported.

Their survey of 42 such officials revealed widely varying opinions on when disclosure should be made, the financial limits that should trigger it, and how much information to share with prospective research subjects, said Dr. Weinfurt of the department of psychiatry at Duke University, Durham, N.C., and his coinvestigators.

“Part of their struggle relates to a lack of clarity regarding the ultimate goals of disclosure,” they wrote. “There is also a lack of systematic data regarding how potential research participants can and will use such information in their decision-making” (J. Law Med. Ethics 2006;34:581–91).

The study was based on personal interviews with eight investigators, 23 review board chairs, and 14 conflict of interest committee chairs. The survey was designed to elicit respondents' understandings of how disclosure is done at their institutions and their thoughts on disclosure, including its risks and benefits to the institution and research subjects.

More than half of those interviewed agreed that disclosure should occur under all circumstances; the rest said disclosure would depend on the degree of the financial relationship. The most commonly expressed reason for disclosing a financial relationship was to facilitate better-informed decision making for potential subjects. Other reasons included trust and transparency issues, reducing liability risk, and managing public perception of the institution.

About 80% of respondents said the disclosure should include the name of the funding source. But some said the name of the company or organization wasn't as important as a description—whether it was a nonprofit organization, pharmaceutical company, or government body, for instance.

They also differed on whether the amount of financial interest should be disclosed. Conflict of interest committee chairs were most likely to want to share this information (93%), while investigators were least likely (63%). Those who expressed concern about disclosing the amount felt that level of detail could become cumbersome or confusing in the informed consent statement, and that research subjects might overestimate the impact that particular amounts might actually have on research outcomes. There was no consensus on what amount should trigger disclosure—the lower limit ranged from $1 to $50,000.

There was general agreement that the nature of the relationship should be disclosed, but no agreement about whether the disclosure should explain the possible impact of those relationships. Again, concern about overcomplicating the consent statement semed to be at the root of these issues. Some respondents said the disclosure should include an explanation of how an unscrupulous investigator might alter the research results.

Most respondents dismissed the idea that disclosure could lower enrollment. There was little sympathy among the group for researchers who complained that full disclosure was an invasion of their financial privacy.

There was also concern about how to best highlight disclosure information without overemphasizing its importance or potential risk to a study's integrity. Some respondents said their consent form highlights the information in bold type, while others place it strategically in the document—at the very beginning, for example. Many also emphasized that the informed consent process should include a discussion of conflict of interest, not just a read-through of the document.

“Our data suggest that it will be difficult to achieve agreement on the issue of substantial understanding of financial interests,” they wrote. There must first be agreement about what risks are important for research participants to understand.

Officials in charge of disclosing financial interests in research agree that disclosure is important, but are confused about how to do so effectively and appropriately, Kevin P. Weinfurt, Ph.D., and his colleagues reported.

Their survey of 42 such officials revealed widely varying opinions on when disclosure should be made, the financial limits that should trigger it, and how much information to share with prospective research subjects, said Dr. Weinfurt of the department of psychiatry at Duke University, Durham, N.C., and his coinvestigators.

“Part of their struggle relates to a lack of clarity regarding the ultimate goals of disclosure,” they wrote. “There is also a lack of systematic data regarding how potential research participants can and will use such information in their decision-making” (J. Law Med. Ethics 2006;34:581–91).

The study was based on personal interviews with eight investigators, 23 review board chairs, and 14 conflict of interest committee chairs. The survey was designed to elicit respondents' understandings of how disclosure is done at their institutions and their thoughts on disclosure, including its risks and benefits to the institution and research subjects.

More than half of those interviewed agreed that disclosure should occur under all circumstances; the rest said disclosure would depend on the degree of the financial relationship. The most commonly expressed reason for disclosing a financial relationship was to facilitate better-informed decision making for potential subjects. Other reasons included trust and transparency issues, reducing liability risk, and managing public perception of the institution.

About 80% of respondents said the disclosure should include the name of the funding source. But some said the name of the company or organization wasn't as important as a description—whether it was a nonprofit organization, pharmaceutical company, or government body, for instance.

They also differed on whether the amount of financial interest should be disclosed. Conflict of interest committee chairs were most likely to want to share this information (93%), while investigators were least likely (63%). Those who expressed concern about disclosing the amount felt that level of detail could become cumbersome or confusing in the informed consent statement, and that research subjects might overestimate the impact that particular amounts might actually have on research outcomes. There was no consensus on what amount should trigger disclosure—the lower limit ranged from $1 to $50,000.

There was general agreement that the nature of the relationship should be disclosed, but no agreement about whether the disclosure should explain the possible impact of those relationships. Again, concern about overcomplicating the consent statement semed to be at the root of these issues. Some respondents said the disclosure should include an explanation of how an unscrupulous investigator might alter the research results.

Most respondents dismissed the idea that disclosure could lower enrollment. There was little sympathy among the group for researchers who complained that full disclosure was an invasion of their financial privacy.

There was also concern about how to best highlight disclosure information without overemphasizing its importance or potential risk to a study's integrity. Some respondents said their consent form highlights the information in bold type, while others place it strategically in the document—at the very beginning, for example. Many also emphasized that the informed consent process should include a discussion of conflict of interest, not just a read-through of the document.

“Our data suggest that it will be difficult to achieve agreement on the issue of substantial understanding of financial interests,” they wrote. There must first be agreement about what risks are important for research participants to understand.

PITTSBURGH – The corpora callosa of individuals with autism are smaller than those of healthy controls both during early childhood and after age 30 years, according to data presented during a poster session at the annual meeting of the Child Neurology Society.

The differences are especially obvious in the genu, rostrum, and splenium–areas with a high density of thin fibers, which are important in higher-order cortical processing.

“Our findings provide new evidence that, in autism, differences in the pattern of neurological development may continue into the aging process,” said Diane L. Williams, Ph.D., who presented the findings.

Dr. Williams of Duquesne University, Pittsburgh, and her colleagues used magnetic resonance imaging to examine the corpora callosa of 80 high-functioning males with autism (aged 9–53 years) and 80 healthy age-matched male controls. Because corpus callosum anatomy has been reported to be affected by handedness and gender, the investigators used only males, and the groups were matched for handedness.

The researchers divided each group into five age categories (10–15.4 years, 15.5–20.4 years, 20.5–25.4 years, 25.5–30.4 years, and 35 years and older). On imaging, the corpus callosum was divided into seven subregions (rostrum, genu, rostral body, anterior midbody, posterior midbody, isthmus, and splenium), and was measured at the midsagittal slice.

After controlling for IQ, age, and total brain volume, the group with autism had reliably smaller corpora callosa than did controls.

The overall difference was driven by significant differences in the youngest and oldest groups compared with their corresponding control groups. Both autism groups had significantly smaller measurements for the total corpus callosum and the rostrum and genu; the oldest group also had reduced measurements in the splenium.

During adolescence and young adulthood, the size differences normalized. “This should not be interpreted, however, to mean that the integrity and composition of the neural structures are the same at that time,” the researchers noted.

Rather, the structure size differences in childhood and later adulthood may reflect a different developmental trajectory, with later maturing and earlier decline than normal controls experienced.

“The suggestion of group differences for the rostrum and genu at early and late ages is consistent with what is known about normal development of these subregions. In normal adults, the anterior white matter, including the genu of the corpus callosum, is the first to decline. In autism, this same developmental pattern may occur, only with a timing difference,” the investigators said.

PITTSBURGH – The corpora callosa of individuals with autism are smaller than those of healthy controls both during early childhood and after age 30 years, according to data presented during a poster session at the annual meeting of the Child Neurology Society.

The differences are especially obvious in the genu, rostrum, and splenium–areas with a high density of thin fibers, which are important in higher-order cortical processing.

“Our findings provide new evidence that, in autism, differences in the pattern of neurological development may continue into the aging process,” said Diane L. Williams, Ph.D., who presented the findings.

Dr. Williams of Duquesne University, Pittsburgh, and her colleagues used magnetic resonance imaging to examine the corpora callosa of 80 high-functioning males with autism (aged 9–53 years) and 80 healthy age-matched male controls. Because corpus callosum anatomy has been reported to be affected by handedness and gender, the investigators used only males, and the groups were matched for handedness.

The researchers divided each group into five age categories (10–15.4 years, 15.5–20.4 years, 20.5–25.4 years, 25.5–30.4 years, and 35 years and older). On imaging, the corpus callosum was divided into seven subregions (rostrum, genu, rostral body, anterior midbody, posterior midbody, isthmus, and splenium), and was measured at the midsagittal slice.

After controlling for IQ, age, and total brain volume, the group with autism had reliably smaller corpora callosa than did controls.

The overall difference was driven by significant differences in the youngest and oldest groups compared with their corresponding control groups. Both autism groups had significantly smaller measurements for the total corpus callosum and the rostrum and genu; the oldest group also had reduced measurements in the splenium.

During adolescence and young adulthood, the size differences normalized. “This should not be interpreted, however, to mean that the integrity and composition of the neural structures are the same at that time,” the researchers noted.

Rather, the structure size differences in childhood and later adulthood may reflect a different developmental trajectory, with later maturing and earlier decline than normal controls experienced.

“The suggestion of group differences for the rostrum and genu at early and late ages is consistent with what is known about normal development of these subregions. In normal adults, the anterior white matter, including the genu of the corpus callosum, is the first to decline. In autism, this same developmental pattern may occur, only with a timing difference,” the investigators said.

PITTSBURGH – The corpora callosa of individuals with autism are smaller than those of healthy controls both during early childhood and after age 30 years, according to data presented during a poster session at the annual meeting of the Child Neurology Society.

The differences are especially obvious in the genu, rostrum, and splenium–areas with a high density of thin fibers, which are important in higher-order cortical processing.

“Our findings provide new evidence that, in autism, differences in the pattern of neurological development may continue into the aging process,” said Diane L. Williams, Ph.D., who presented the findings.

Dr. Williams of Duquesne University, Pittsburgh, and her colleagues used magnetic resonance imaging to examine the corpora callosa of 80 high-functioning males with autism (aged 9–53 years) and 80 healthy age-matched male controls. Because corpus callosum anatomy has been reported to be affected by handedness and gender, the investigators used only males, and the groups were matched for handedness.

The researchers divided each group into five age categories (10–15.4 years, 15.5–20.4 years, 20.5–25.4 years, 25.5–30.4 years, and 35 years and older). On imaging, the corpus callosum was divided into seven subregions (rostrum, genu, rostral body, anterior midbody, posterior midbody, isthmus, and splenium), and was measured at the midsagittal slice.

After controlling for IQ, age, and total brain volume, the group with autism had reliably smaller corpora callosa than did controls.

The overall difference was driven by significant differences in the youngest and oldest groups compared with their corresponding control groups. Both autism groups had significantly smaller measurements for the total corpus callosum and the rostrum and genu; the oldest group also had reduced measurements in the splenium.

During adolescence and young adulthood, the size differences normalized. “This should not be interpreted, however, to mean that the integrity and composition of the neural structures are the same at that time,” the researchers noted.

Rather, the structure size differences in childhood and later adulthood may reflect a different developmental trajectory, with later maturing and earlier decline than normal controls experienced.

“The suggestion of group differences for the rostrum and genu at early and late ages is consistent with what is known about normal development of these subregions. In normal adults, the anterior white matter, including the genu of the corpus callosum, is the first to decline. In autism, this same developmental pattern may occur, only with a timing difference,” the investigators said.

PITTSBURGH – Treatment-limiting adverse events occurred in more than 30% of patients who received a vagus nerve stimulator for the treatment of seizure disorders, Dr. Phillip Pearl reported at the annual meeting of the Child Neurology Society.

The number of adverse events may increase even more as vagus nerve stimulator (VNS) devices become more common among new populations of patients with seizure disorders, said Dr. Pearl. “I think this is probably the tip of the iceberg and that we will be seeing more cases as more people receive this device and as the longevity of VNS therapy increases beyond what was studied for the initial approval.”

Dr. Pearl reported adverse events among 62 patients who had VNS devices implanted in 1998–2005 at the Children's National Medical Center, Washington, where he is a pediatric neurologist. The patients ranged in age from 3 to 29 years (median 12 years). The median duration of therapy was 40 months (range 1–96 months).

Of the 62 patients, 35% (22 patients) had at least one clinically significant adverse event. The most common were persistent drooling (six), coughing (five), throat discomfort or spasms (four), and dysphagia (three). Two patients had difficulty breathing, with one requiring device removal. Two experienced vomiting while the VNS current was delivered, and two more experienced vocal cord weakness. All of these adverse events required some limiting of the current output of the device. Two more patients experienced axillary wound infections that required oral antibiotic treatment.

Of the patients with adverse events, eight needed nonroutine surgical intervention. The device was removed from five patients (8%), including a 13-year-old girl who developed serious complications from a wound infection requiring intravenous antibiotics. She also needed a percutaneous endoscopic gastronomy tube because of vocal cord paralysis and persistent dysphagia. The other four explantations were necessary because of persistent problems with breathing, coughing, or throat discomfort.

There were also two lead failures, Dr. Pearl said. One was discovered during a routine device interrogation more than 7 years after the initial implant. The other one was discovered after seizure control worsened.

In addition to these adverse events, there were two patients who experienced unique unanticipated problems.

One was a 13-year-old boy who had received the implant for intractable generalized seizures and was seen at an emergency department for convulsive status.

Peripheral vein access was limited; an emergency physician searching for an access site misidentified the VNS wire in the boy's neck as the jugular vein.

“The wire was stabbed several times until it became apparent that it was not a vein,” Dr. Pearl said. Interrogation of the device a few days later showed no evidence of malfunction. One year later, the device did malfunction; the patient experienced increased seizures and needed a replacement.

Finally, Dr. Pearl said, a 25-year-old man with a VNS for intractable absence seizures began to experience tingling in the left side of his neck about 3 months after implantation. There was no indication that the device was malfunctioning, but the tingling did not occur when it was turned off. Subsequent x-rays showed that there was no strain-relief loop in the VNS wire located over the sternocleidomastoid muscle. Rather than have a revision, the patient continues to tolerate the intermittent sensations, Dr. Pearl said.

PITTSBURGH – Treatment-limiting adverse events occurred in more than 30% of patients who received a vagus nerve stimulator for the treatment of seizure disorders, Dr. Phillip Pearl reported at the annual meeting of the Child Neurology Society.

The number of adverse events may increase even more as vagus nerve stimulator (VNS) devices become more common among new populations of patients with seizure disorders, said Dr. Pearl. “I think this is probably the tip of the iceberg and that we will be seeing more cases as more people receive this device and as the longevity of VNS therapy increases beyond what was studied for the initial approval.”

Dr. Pearl reported adverse events among 62 patients who had VNS devices implanted in 1998–2005 at the Children's National Medical Center, Washington, where he is a pediatric neurologist. The patients ranged in age from 3 to 29 years (median 12 years). The median duration of therapy was 40 months (range 1–96 months).

Of the 62 patients, 35% (22 patients) had at least one clinically significant adverse event. The most common were persistent drooling (six), coughing (five), throat discomfort or spasms (four), and dysphagia (three). Two patients had difficulty breathing, with one requiring device removal. Two experienced vomiting while the VNS current was delivered, and two more experienced vocal cord weakness. All of these adverse events required some limiting of the current output of the device. Two more patients experienced axillary wound infections that required oral antibiotic treatment.

Of the patients with adverse events, eight needed nonroutine surgical intervention. The device was removed from five patients (8%), including a 13-year-old girl who developed serious complications from a wound infection requiring intravenous antibiotics. She also needed a percutaneous endoscopic gastronomy tube because of vocal cord paralysis and persistent dysphagia. The other four explantations were necessary because of persistent problems with breathing, coughing, or throat discomfort.

There were also two lead failures, Dr. Pearl said. One was discovered during a routine device interrogation more than 7 years after the initial implant. The other one was discovered after seizure control worsened.

In addition to these adverse events, there were two patients who experienced unique unanticipated problems.

One was a 13-year-old boy who had received the implant for intractable generalized seizures and was seen at an emergency department for convulsive status.

Peripheral vein access was limited; an emergency physician searching for an access site misidentified the VNS wire in the boy's neck as the jugular vein.

“The wire was stabbed several times until it became apparent that it was not a vein,” Dr. Pearl said. Interrogation of the device a few days later showed no evidence of malfunction. One year later, the device did malfunction; the patient experienced increased seizures and needed a replacement.

Finally, Dr. Pearl said, a 25-year-old man with a VNS for intractable absence seizures began to experience tingling in the left side of his neck about 3 months after implantation. There was no indication that the device was malfunctioning, but the tingling did not occur when it was turned off. Subsequent x-rays showed that there was no strain-relief loop in the VNS wire located over the sternocleidomastoid muscle. Rather than have a revision, the patient continues to tolerate the intermittent sensations, Dr. Pearl said.

PITTSBURGH – Treatment-limiting adverse events occurred in more than 30% of patients who received a vagus nerve stimulator for the treatment of seizure disorders, Dr. Phillip Pearl reported at the annual meeting of the Child Neurology Society.

The number of adverse events may increase even more as vagus nerve stimulator (VNS) devices become more common among new populations of patients with seizure disorders, said Dr. Pearl. “I think this is probably the tip of the iceberg and that we will be seeing more cases as more people receive this device and as the longevity of VNS therapy increases beyond what was studied for the initial approval.”

Dr. Pearl reported adverse events among 62 patients who had VNS devices implanted in 1998–2005 at the Children's National Medical Center, Washington, where he is a pediatric neurologist. The patients ranged in age from 3 to 29 years (median 12 years). The median duration of therapy was 40 months (range 1–96 months).

Of the 62 patients, 35% (22 patients) had at least one clinically significant adverse event. The most common were persistent drooling (six), coughing (five), throat discomfort or spasms (four), and dysphagia (three). Two patients had difficulty breathing, with one requiring device removal. Two experienced vomiting while the VNS current was delivered, and two more experienced vocal cord weakness. All of these adverse events required some limiting of the current output of the device. Two more patients experienced axillary wound infections that required oral antibiotic treatment.

Of the patients with adverse events, eight needed nonroutine surgical intervention. The device was removed from five patients (8%), including a 13-year-old girl who developed serious complications from a wound infection requiring intravenous antibiotics. She also needed a percutaneous endoscopic gastronomy tube because of vocal cord paralysis and persistent dysphagia. The other four explantations were necessary because of persistent problems with breathing, coughing, or throat discomfort.

There were also two lead failures, Dr. Pearl said. One was discovered during a routine device interrogation more than 7 years after the initial implant. The other one was discovered after seizure control worsened.

In addition to these adverse events, there were two patients who experienced unique unanticipated problems.

One was a 13-year-old boy who had received the implant for intractable generalized seizures and was seen at an emergency department for convulsive status.

Peripheral vein access was limited; an emergency physician searching for an access site misidentified the VNS wire in the boy's neck as the jugular vein.

“The wire was stabbed several times until it became apparent that it was not a vein,” Dr. Pearl said. Interrogation of the device a few days later showed no evidence of malfunction. One year later, the device did malfunction; the patient experienced increased seizures and needed a replacement.

Finally, Dr. Pearl said, a 25-year-old man with a VNS for intractable absence seizures began to experience tingling in the left side of his neck about 3 months after implantation. There was no indication that the device was malfunctioning, but the tingling did not occur when it was turned off. Subsequent x-rays showed that there was no strain-relief loop in the VNS wire located over the sternocleidomastoid muscle. Rather than have a revision, the patient continues to tolerate the intermittent sensations, Dr. Pearl said.

MADRID – Oxcarbazepine appears to significantly decrease hypersexual behavior in patients with Alzheimer's disease, Dr. Joshua Shua-Haim reported in a poster presented at the 10th International Conference on Alzheimer's Disease and Related Disorders.

All 11 men in the small pilot study showed improvement in the behavior after 2 weeks of treatment, noted Dr. Shua-Haim, who is with the Jersey Shore University Medical Center in Neptune, N.J.

All of the patients lived in a special care unit in an assisted living facility.

Treatment began with 150 mg oxcarbazepine daily. The dose was titrated by 150 mg/day, given in two divided doses, until the behavior ceased or a maximum of 900 mg/day was reached, Dr. Shua-Haim wrote.

Hypersexual behavior resolved in all 11 patients after they received an average dose of 600–750 mg/day, given in two doses. No adverse events were reported, and there were no changes in blood chemistry.

MADRID – Oxcarbazepine appears to significantly decrease hypersexual behavior in patients with Alzheimer's disease, Dr. Joshua Shua-Haim reported in a poster presented at the 10th International Conference on Alzheimer's Disease and Related Disorders.

All 11 men in the small pilot study showed improvement in the behavior after 2 weeks of treatment, noted Dr. Shua-Haim, who is with the Jersey Shore University Medical Center in Neptune, N.J.

All of the patients lived in a special care unit in an assisted living facility.

Treatment began with 150 mg oxcarbazepine daily. The dose was titrated by 150 mg/day, given in two divided doses, until the behavior ceased or a maximum of 900 mg/day was reached, Dr. Shua-Haim wrote.

Hypersexual behavior resolved in all 11 patients after they received an average dose of 600–750 mg/day, given in two doses. No adverse events were reported, and there were no changes in blood chemistry.

MADRID – Oxcarbazepine appears to significantly decrease hypersexual behavior in patients with Alzheimer's disease, Dr. Joshua Shua-Haim reported in a poster presented at the 10th International Conference on Alzheimer's Disease and Related Disorders.

All 11 men in the small pilot study showed improvement in the behavior after 2 weeks of treatment, noted Dr. Shua-Haim, who is with the Jersey Shore University Medical Center in Neptune, N.J.

All of the patients lived in a special care unit in an assisted living facility.

Treatment began with 150 mg oxcarbazepine daily. The dose was titrated by 150 mg/day, given in two divided doses, until the behavior ceased or a maximum of 900 mg/day was reached, Dr. Shua-Haim wrote.

Hypersexual behavior resolved in all 11 patients after they received an average dose of 600–750 mg/day, given in two doses. No adverse events were reported, and there were no changes in blood chemistry.

BARCELONA — Hydroxyethyl starch solutions can't be recommended for fluid resuscitation in patients with severe sepsis or septic shock, or in those at risk of renal problems, researchers said at the annual congress of the European Society for Intensive Care Medicine.

The starch solutions are associated with higher rates of acute renal failure and increased 90-day mortality in these patients, especially in those who receive more than the highest recommended dosage of 22 mL/kg of body weight, said Dr. Frank Brunkhorst of the Friedrich Schiller University of Jena (Germany).

Dr. Brunkhorst, who also manages the German Sepsis Society, reported the interim results of the Influence of Colloid vs. Crystalloid Volume Resuscitation in Patients with Severe Sepsis and Septic Shock (VISEP) study.

VISEP, a phase III trial, randomized patients to volume replacement with either 10% hydroxyethyl starch (HES) 200/0.5 solution (10% Hemohes) or Ringer's lactate solution.

The study was powered for 1,200 patients, but it was suspended after the first interim analysis of 600 showed trends of increased renal failure and mortality in the HES group, Dr. Brunkhorst said.

All patients in the study had either severe sepsis or septic shock; their mean age was 64 years. The mean Acute Physiology and Chronic Health Evaluation II score was 20, and the mean Simplified Acute Physiology Score (version II) was 53.

Hemodynamic stabilization occurred significantly faster in the HES group. Mortality at 28 days was slightly but not significantly higher in the HES group, compared with the Ringer's lactate group (27% vs. 24%), a trend repeated for 90-day mortality (41% HES vs. 34% Ringer's lactate).

There were no significant differences in the Sequential Organ Failure Assessment scores overall.

However, the coagulation and renal subscores were significantly higher in the HES group, Dr. Brunkhorst said. In addition, almost twice as many HES as Ringer's patients needed hemodialysis during their treatment (31% vs. 19%), with a total of 650 days of dialysis in the HES group and 321 days in the Ringer's group.

Acute renal failure rates were also significantly higher in the HES group (35% vs. 23%).

The highest recommended dosage of HES (22 mL/kg) was exceeded in 99 patients. A subanalysis of this group identified an increase in dose-dependent mortality at 90 days: 75% of those who exceeded the dosage and 49% of those who did not died. “This was highly statistically significant,” Dr. Brunkhorst said.

No previous study has identified this significantly increased mortality risk in patients who receive high doses of HES, he said—probably because the observation period was too short. “All the other studies had a follow-up of only a few days. This was a phenomenon observed only after 3 weeks,” Dr. Brunkhorst said.

In 2003, when the VISEP study began, 10% HES was the lightest molecular weight and most rapidly degrading colloidal fluid replacement solution available, said Dr. Konrad Reinhart, a coinvestigator of the VISEP trial. Since then, lighter solutions have come to market.

However, he said, no studies have demonstrated enough treatment superiority to convince him to use any colloidal solution instead of Ringer's.

There are many case reports of pruritic dermatitis associated with starch deposits in the dermis.

Autopsy reports have also shown starch deposits in kidney and liver that persisted for more than 10 years after HES treatment, said Dr. Reinhart, director of the department of anesthesiology and intensive care medicine at the University Hospital of the Friedrich Schiller University of Jena.

Dr. Reinhart is also not convinced that acute renal failure is the only factor involved in the increased risk of death in HES patients.

“Several case reports have looked at foamy macrophage syndrome in these patients,” he said (Ann. Int. Med. 2002;137:1013–4), adding that his institution has restricted the use of starch solutions. “We have stopped using them in our unit, and I won't use them at all in sepsis patients,” Dr. Reinhart said.

“No data have ever demonstrated a beneficial effect [over Ringer's], but a lot have demonstrated harm.”

BARCELONA — Hydroxyethyl starch solutions can't be recommended for fluid resuscitation in patients with severe sepsis or septic shock, or in those at risk of renal problems, researchers said at the annual congress of the European Society for Intensive Care Medicine.

The starch solutions are associated with higher rates of acute renal failure and increased 90-day mortality in these patients, especially in those who receive more than the highest recommended dosage of 22 mL/kg of body weight, said Dr. Frank Brunkhorst of the Friedrich Schiller University of Jena (Germany).

Dr. Brunkhorst, who also manages the German Sepsis Society, reported the interim results of the Influence of Colloid vs. Crystalloid Volume Resuscitation in Patients with Severe Sepsis and Septic Shock (VISEP) study.

VISEP, a phase III trial, randomized patients to volume replacement with either 10% hydroxyethyl starch (HES) 200/0.5 solution (10% Hemohes) or Ringer's lactate solution.

The study was powered for 1,200 patients, but it was suspended after the first interim analysis of 600 showed trends of increased renal failure and mortality in the HES group, Dr. Brunkhorst said.

All patients in the study had either severe sepsis or septic shock; their mean age was 64 years. The mean Acute Physiology and Chronic Health Evaluation II score was 20, and the mean Simplified Acute Physiology Score (version II) was 53.

Hemodynamic stabilization occurred significantly faster in the HES group. Mortality at 28 days was slightly but not significantly higher in the HES group, compared with the Ringer's lactate group (27% vs. 24%), a trend repeated for 90-day mortality (41% HES vs. 34% Ringer's lactate).

There were no significant differences in the Sequential Organ Failure Assessment scores overall.

However, the coagulation and renal subscores were significantly higher in the HES group, Dr. Brunkhorst said. In addition, almost twice as many HES as Ringer's patients needed hemodialysis during their treatment (31% vs. 19%), with a total of 650 days of dialysis in the HES group and 321 days in the Ringer's group.

Acute renal failure rates were also significantly higher in the HES group (35% vs. 23%).

The highest recommended dosage of HES (22 mL/kg) was exceeded in 99 patients. A subanalysis of this group identified an increase in dose-dependent mortality at 90 days: 75% of those who exceeded the dosage and 49% of those who did not died. “This was highly statistically significant,” Dr. Brunkhorst said.

No previous study has identified this significantly increased mortality risk in patients who receive high doses of HES, he said—probably because the observation period was too short. “All the other studies had a follow-up of only a few days. This was a phenomenon observed only after 3 weeks,” Dr. Brunkhorst said.

In 2003, when the VISEP study began, 10% HES was the lightest molecular weight and most rapidly degrading colloidal fluid replacement solution available, said Dr. Konrad Reinhart, a coinvestigator of the VISEP trial. Since then, lighter solutions have come to market.

However, he said, no studies have demonstrated enough treatment superiority to convince him to use any colloidal solution instead of Ringer's.

There are many case reports of pruritic dermatitis associated with starch deposits in the dermis.

Autopsy reports have also shown starch deposits in kidney and liver that persisted for more than 10 years after HES treatment, said Dr. Reinhart, director of the department of anesthesiology and intensive care medicine at the University Hospital of the Friedrich Schiller University of Jena.

Dr. Reinhart is also not convinced that acute renal failure is the only factor involved in the increased risk of death in HES patients.

“Several case reports have looked at foamy macrophage syndrome in these patients,” he said (Ann. Int. Med. 2002;137:1013–4), adding that his institution has restricted the use of starch solutions. “We have stopped using them in our unit, and I won't use them at all in sepsis patients,” Dr. Reinhart said.

“No data have ever demonstrated a beneficial effect [over Ringer's], but a lot have demonstrated harm.”

BARCELONA — Hydroxyethyl starch solutions can't be recommended for fluid resuscitation in patients with severe sepsis or septic shock, or in those at risk of renal problems, researchers said at the annual congress of the European Society for Intensive Care Medicine.

The starch solutions are associated with higher rates of acute renal failure and increased 90-day mortality in these patients, especially in those who receive more than the highest recommended dosage of 22 mL/kg of body weight, said Dr. Frank Brunkhorst of the Friedrich Schiller University of Jena (Germany).

Dr. Brunkhorst, who also manages the German Sepsis Society, reported the interim results of the Influence of Colloid vs. Crystalloid Volume Resuscitation in Patients with Severe Sepsis and Septic Shock (VISEP) study.

VISEP, a phase III trial, randomized patients to volume replacement with either 10% hydroxyethyl starch (HES) 200/0.5 solution (10% Hemohes) or Ringer's lactate solution.

The study was powered for 1,200 patients, but it was suspended after the first interim analysis of 600 showed trends of increased renal failure and mortality in the HES group, Dr. Brunkhorst said.

All patients in the study had either severe sepsis or septic shock; their mean age was 64 years. The mean Acute Physiology and Chronic Health Evaluation II score was 20, and the mean Simplified Acute Physiology Score (version II) was 53.

Hemodynamic stabilization occurred significantly faster in the HES group. Mortality at 28 days was slightly but not significantly higher in the HES group, compared with the Ringer's lactate group (27% vs. 24%), a trend repeated for 90-day mortality (41% HES vs. 34% Ringer's lactate).

There were no significant differences in the Sequential Organ Failure Assessment scores overall.

However, the coagulation and renal subscores were significantly higher in the HES group, Dr. Brunkhorst said. In addition, almost twice as many HES as Ringer's patients needed hemodialysis during their treatment (31% vs. 19%), with a total of 650 days of dialysis in the HES group and 321 days in the Ringer's group.

Acute renal failure rates were also significantly higher in the HES group (35% vs. 23%).

The highest recommended dosage of HES (22 mL/kg) was exceeded in 99 patients. A subanalysis of this group identified an increase in dose-dependent mortality at 90 days: 75% of those who exceeded the dosage and 49% of those who did not died. “This was highly statistically significant,” Dr. Brunkhorst said.

No previous study has identified this significantly increased mortality risk in patients who receive high doses of HES, he said—probably because the observation period was too short. “All the other studies had a follow-up of only a few days. This was a phenomenon observed only after 3 weeks,” Dr. Brunkhorst said.

In 2003, when the VISEP study began, 10% HES was the lightest molecular weight and most rapidly degrading colloidal fluid replacement solution available, said Dr. Konrad Reinhart, a coinvestigator of the VISEP trial. Since then, lighter solutions have come to market.

However, he said, no studies have demonstrated enough treatment superiority to convince him to use any colloidal solution instead of Ringer's.

There are many case reports of pruritic dermatitis associated with starch deposits in the dermis.

Autopsy reports have also shown starch deposits in kidney and liver that persisted for more than 10 years after HES treatment, said Dr. Reinhart, director of the department of anesthesiology and intensive care medicine at the University Hospital of the Friedrich Schiller University of Jena.

Dr. Reinhart is also not convinced that acute renal failure is the only factor involved in the increased risk of death in HES patients.

“Several case reports have looked at foamy macrophage syndrome in these patients,” he said (Ann. Int. Med. 2002;137:1013–4), adding that his institution has restricted the use of starch solutions. “We have stopped using them in our unit, and I won't use them at all in sepsis patients,” Dr. Reinhart said.

“No data have ever demonstrated a beneficial effect [over Ringer's], but a lot have demonstrated harm.”