AAN Annual Meeting

NEW ORLEANS – Advanced Parkinson’s disease patients had significantly less "off" time – without increased dyskinesia – when they were treated with levodopa-carbidopa intestinal gel rather than immediate-release oral levodopa-carbidopa in a phase III, randomized trial sponsored by the gel’s maker, Abbott Laboratories.

The trial is part of Abbott’s phase III development program for the drug; the company plans to submit an approval package to the Food and Drug Administration this year. The gel has been on the market for several years in Europe and elsewhere, where it has been sold under the name Duodopa.

Commenting on his blog, the medical director of the National Parkinson Foundation, Dr. Michael Okun, wrote, "Duodopa will likely be a great choice for many patients with on-off fluctuations, and will in most cases allow discontinuation of oral PD drugs."

"However, Duodopa does require a very attentive caregiver who will need to attend to device management, skin management (for the tube), and also attend to medication refills. Early studies of Duodopa have revealed high rates of device-related problems with the intestinal tube," such as clogging, kinking, and moving out of the correct location, said Dr. Okun, codirector of the center for movement disorders and neurorestoration at the University of Florida, Gainesville.

The idea is that by infusing levodopa-carbidopa continuously, patients can avoid the fluctuating plasma levodopa levels associated with oral formulations.

Perhaps those fluctuating levels induce molecular and physiological changes in dopamine receptors "that ultimately result in motor complications. This has led to the theory that if you can deliver levodopa more continuously, it would be more physiologic and might avoid these problems," said lead investigator Dr. Warren Olanow, director of the Bendheim Parkinson Center at the Mount Sinai Medical Center in New York City. He presented the findings on behalf of Abbott.

The gel is delivered through a surgically placed gastrojejunostomy tube, which is connected to a portable pump that is worn around the waist for 16 hours a day.

In the 12-week trial, 37 patients with motor complications that were inadequately controlled by oral medications were randomized to levodopa-carbidopa intestinal gel (LCIG) plus placebo capsules; 34 were randomized to levodopa-carbidopa immediate release (LC-IR) tablets plus placebo gel infusions.

The LCIG group had a mean 1.91 hours less "off" time each day than did the LC-IR group (P = .0015), and a mean 1.86 hours more daily "on" time without troublesome dyskinesia (P = .0059).

But the tube placement caused complications in about half of the patients, and 23 (32.4%) had pain with the procedure. In all, 19 (51%) LCIG patients and 11 (32%) LC-IR patients complained of abdominal pain; 11 (30%) LCIG patients and 7 (21%) LC-IR patients complained of nausea. Although common, the side effects were mostly transient, Dr. Olanow said.

Overall, the benefits of the gel "in a patient group that cannot be satisfactorily controlled with standard levodopa represent an important step forward in our efforts to treat advanced PD patients," he said.

With several years of use in Europe and elsewhere, the gel already has a fairly robust body of published literature. In a small, randomized, pharmacokinetics study that compared it to sustained-release oral levodopa-carbidopa, the gel patients had steadier levodopa plasma concentrations and greater "on" time (Clin. Neuropharmacol. 2003;26:156-63).

Another trial compared subthalamic nucleus deep brain stimulation (DBS) in 20 patients to Duodopa in 20 others who were unsuitable for DBS neurosurgery. Both groups had a significant improvement in Unified Parkinson’s Disease Rating Scale scores and considerable off-time reduction. Only the DBS group had a significant improvement in dyskinesia duration and disability, but also a significant drop in verbal fluency that was not seen with Duodopa. Duodopa, however, had more procedure-related complications (Mov. Disord. 2011;26:664-70).

Dr. Olanow has received personal compensation for activities with Abbott, Teva/Lundbeck, Novartis/Orion, Ceregene, Merck Serono, Ipsen, and Impax. He holds stock or stock options in Clintrex and Ceregene. Dr. Okun has no current, relevant disclosures.

NEW ORLEANS – Advanced Parkinson’s disease patients had significantly less "off" time – without increased dyskinesia – when they were treated with levodopa-carbidopa intestinal gel rather than immediate-release oral levodopa-carbidopa in a phase III, randomized trial sponsored by the gel’s maker, Abbott Laboratories.

The trial is part of Abbott’s phase III development program for the drug; the company plans to submit an approval package to the Food and Drug Administration this year. The gel has been on the market for several years in Europe and elsewhere, where it has been sold under the name Duodopa.

Commenting on his blog, the medical director of the National Parkinson Foundation, Dr. Michael Okun, wrote, "Duodopa will likely be a great choice for many patients with on-off fluctuations, and will in most cases allow discontinuation of oral PD drugs."

"However, Duodopa does require a very attentive caregiver who will need to attend to device management, skin management (for the tube), and also attend to medication refills. Early studies of Duodopa have revealed high rates of device-related problems with the intestinal tube," such as clogging, kinking, and moving out of the correct location, said Dr. Okun, codirector of the center for movement disorders and neurorestoration at the University of Florida, Gainesville.

The idea is that by infusing levodopa-carbidopa continuously, patients can avoid the fluctuating plasma levodopa levels associated with oral formulations.

Perhaps those fluctuating levels induce molecular and physiological changes in dopamine receptors "that ultimately result in motor complications. This has led to the theory that if you can deliver levodopa more continuously, it would be more physiologic and might avoid these problems," said lead investigator Dr. Warren Olanow, director of the Bendheim Parkinson Center at the Mount Sinai Medical Center in New York City. He presented the findings on behalf of Abbott.

The gel is delivered through a surgically placed gastrojejunostomy tube, which is connected to a portable pump that is worn around the waist for 16 hours a day.

In the 12-week trial, 37 patients with motor complications that were inadequately controlled by oral medications were randomized to levodopa-carbidopa intestinal gel (LCIG) plus placebo capsules; 34 were randomized to levodopa-carbidopa immediate release (LC-IR) tablets plus placebo gel infusions.

The LCIG group had a mean 1.91 hours less "off" time each day than did the LC-IR group (P = .0015), and a mean 1.86 hours more daily "on" time without troublesome dyskinesia (P = .0059).

But the tube placement caused complications in about half of the patients, and 23 (32.4%) had pain with the procedure. In all, 19 (51%) LCIG patients and 11 (32%) LC-IR patients complained of abdominal pain; 11 (30%) LCIG patients and 7 (21%) LC-IR patients complained of nausea. Although common, the side effects were mostly transient, Dr. Olanow said.

Overall, the benefits of the gel "in a patient group that cannot be satisfactorily controlled with standard levodopa represent an important step forward in our efforts to treat advanced PD patients," he said.

With several years of use in Europe and elsewhere, the gel already has a fairly robust body of published literature. In a small, randomized, pharmacokinetics study that compared it to sustained-release oral levodopa-carbidopa, the gel patients had steadier levodopa plasma concentrations and greater "on" time (Clin. Neuropharmacol. 2003;26:156-63).

Another trial compared subthalamic nucleus deep brain stimulation (DBS) in 20 patients to Duodopa in 20 others who were unsuitable for DBS neurosurgery. Both groups had a significant improvement in Unified Parkinson’s Disease Rating Scale scores and considerable off-time reduction. Only the DBS group had a significant improvement in dyskinesia duration and disability, but also a significant drop in verbal fluency that was not seen with Duodopa. Duodopa, however, had more procedure-related complications (Mov. Disord. 2011;26:664-70).

Dr. Olanow has received personal compensation for activities with Abbott, Teva/Lundbeck, Novartis/Orion, Ceregene, Merck Serono, Ipsen, and Impax. He holds stock or stock options in Clintrex and Ceregene. Dr. Okun has no current, relevant disclosures.

NEW ORLEANS – Advanced Parkinson’s disease patients had significantly less "off" time – without increased dyskinesia – when they were treated with levodopa-carbidopa intestinal gel rather than immediate-release oral levodopa-carbidopa in a phase III, randomized trial sponsored by the gel’s maker, Abbott Laboratories.

The trial is part of Abbott’s phase III development program for the drug; the company plans to submit an approval package to the Food and Drug Administration this year. The gel has been on the market for several years in Europe and elsewhere, where it has been sold under the name Duodopa.

Commenting on his blog, the medical director of the National Parkinson Foundation, Dr. Michael Okun, wrote, "Duodopa will likely be a great choice for many patients with on-off fluctuations, and will in most cases allow discontinuation of oral PD drugs."

"However, Duodopa does require a very attentive caregiver who will need to attend to device management, skin management (for the tube), and also attend to medication refills. Early studies of Duodopa have revealed high rates of device-related problems with the intestinal tube," such as clogging, kinking, and moving out of the correct location, said Dr. Okun, codirector of the center for movement disorders and neurorestoration at the University of Florida, Gainesville.

The idea is that by infusing levodopa-carbidopa continuously, patients can avoid the fluctuating plasma levodopa levels associated with oral formulations.

Perhaps those fluctuating levels induce molecular and physiological changes in dopamine receptors "that ultimately result in motor complications. This has led to the theory that if you can deliver levodopa more continuously, it would be more physiologic and might avoid these problems," said lead investigator Dr. Warren Olanow, director of the Bendheim Parkinson Center at the Mount Sinai Medical Center in New York City. He presented the findings on behalf of Abbott.

The gel is delivered through a surgically placed gastrojejunostomy tube, which is connected to a portable pump that is worn around the waist for 16 hours a day.

In the 12-week trial, 37 patients with motor complications that were inadequately controlled by oral medications were randomized to levodopa-carbidopa intestinal gel (LCIG) plus placebo capsules; 34 were randomized to levodopa-carbidopa immediate release (LC-IR) tablets plus placebo gel infusions.

The LCIG group had a mean 1.91 hours less "off" time each day than did the LC-IR group (P = .0015), and a mean 1.86 hours more daily "on" time without troublesome dyskinesia (P = .0059).

But the tube placement caused complications in about half of the patients, and 23 (32.4%) had pain with the procedure. In all, 19 (51%) LCIG patients and 11 (32%) LC-IR patients complained of abdominal pain; 11 (30%) LCIG patients and 7 (21%) LC-IR patients complained of nausea. Although common, the side effects were mostly transient, Dr. Olanow said.

Overall, the benefits of the gel "in a patient group that cannot be satisfactorily controlled with standard levodopa represent an important step forward in our efforts to treat advanced PD patients," he said.

With several years of use in Europe and elsewhere, the gel already has a fairly robust body of published literature. In a small, randomized, pharmacokinetics study that compared it to sustained-release oral levodopa-carbidopa, the gel patients had steadier levodopa plasma concentrations and greater "on" time (Clin. Neuropharmacol. 2003;26:156-63).

Another trial compared subthalamic nucleus deep brain stimulation (DBS) in 20 patients to Duodopa in 20 others who were unsuitable for DBS neurosurgery. Both groups had a significant improvement in Unified Parkinson’s Disease Rating Scale scores and considerable off-time reduction. Only the DBS group had a significant improvement in dyskinesia duration and disability, but also a significant drop in verbal fluency that was not seen with Duodopa. Duodopa, however, had more procedure-related complications (Mov. Disord. 2011;26:664-70).

Dr. Olanow has received personal compensation for activities with Abbott, Teva/Lundbeck, Novartis/Orion, Ceregene, Merck Serono, Ipsen, and Impax. He holds stock or stock options in Clintrex and Ceregene. Dr. Okun has no current, relevant disclosures.

NEW ORLEANS – Use of a variation on the traditional medical home model for pediatric neurology cases in an underserved population led to a decrease in hospitalizations and less frequent use of the emergency department in a study that compared outcomes and health care resource utilization between the two models.

The new model also led to faster referrals and fewer broken appointments, said Dr. David Urion, director of the learning disabilities and behavioral neurology program at Children’s Hospital in Boston, who led the study.

It is already well known that access to primary care is not as great for Americans who have a lower socioeconomic status, he said. The rate of access is even lower among non-English speakers, hovering around 70%, Dr. Urion said at the annual meeting of the American Academy of Neurology.

Access to specialists is generally lower than access to primary care.

In Boston, the Community Health Center movement has tried to improve access, in part by using a medical home model. Dr. Urion and his colleagues studied two different medical home models utilized by two centers – the South End Community Health Center and the Martha Eliot Community Health Center. Both are located in predominantly Hispanic and poorer areas.

One medical home model was what would be considered "traditional," in which patients were referred by the health center to a specialist at a hospital outpatient clinic. The other was an "itinerant" model, where the specialist would hold office hours at the center on a set day of the week. Patients were referred by a primary care physician.

From 2007 to 2011, the traditional model saw about 105 patients a year, while the itinerant model had about 103 patients a year. This was the equivalent of one session per week per provider, Dr. Urion said.

For the traditional model, the median time to an appointment was 90 days. The itinerant model cut that by 76 days to a wait of only 14 days for an appointment. Only 67% of new patients kept their appointment with the traditional model, compared with 95% of those in the nontraditional model. For existing patients, only 50% kept an appointment in the traditional model, compared with 85% of those in the newer model.

The use of the emergency department was reduced 18-fold, with 1.8 visits per patient-year for the traditional model and 0.1 per patient-year for the nontraditional model. Hospitalization days per neurologic diagnosis were 0.4 days per patient-year for the traditional model, compared with 0.1 for the itinerant model.

There was a huge difference in costs. The traditional model’s charges were $14,650 per year, compared with only $1,850 for the itinerant model.

Physicians in the itinerant model also won out financially. With missed appointments and follow-ups, those in the traditional model lost $17,250 a year, compared with only $4,080 a year with the itinerant model.

Thus, the itinerant model delivered superior care, said Dr. Urion, who reported having no relevant disclosures.

NEW ORLEANS – Use of a variation on the traditional medical home model for pediatric neurology cases in an underserved population led to a decrease in hospitalizations and less frequent use of the emergency department in a study that compared outcomes and health care resource utilization between the two models.

The new model also led to faster referrals and fewer broken appointments, said Dr. David Urion, director of the learning disabilities and behavioral neurology program at Children’s Hospital in Boston, who led the study.

It is already well known that access to primary care is not as great for Americans who have a lower socioeconomic status, he said. The rate of access is even lower among non-English speakers, hovering around 70%, Dr. Urion said at the annual meeting of the American Academy of Neurology.

Access to specialists is generally lower than access to primary care.

In Boston, the Community Health Center movement has tried to improve access, in part by using a medical home model. Dr. Urion and his colleagues studied two different medical home models utilized by two centers – the South End Community Health Center and the Martha Eliot Community Health Center. Both are located in predominantly Hispanic and poorer areas.

One medical home model was what would be considered "traditional," in which patients were referred by the health center to a specialist at a hospital outpatient clinic. The other was an "itinerant" model, where the specialist would hold office hours at the center on a set day of the week. Patients were referred by a primary care physician.

From 2007 to 2011, the traditional model saw about 105 patients a year, while the itinerant model had about 103 patients a year. This was the equivalent of one session per week per provider, Dr. Urion said.

For the traditional model, the median time to an appointment was 90 days. The itinerant model cut that by 76 days to a wait of only 14 days for an appointment. Only 67% of new patients kept their appointment with the traditional model, compared with 95% of those in the nontraditional model. For existing patients, only 50% kept an appointment in the traditional model, compared with 85% of those in the newer model.

The use of the emergency department was reduced 18-fold, with 1.8 visits per patient-year for the traditional model and 0.1 per patient-year for the nontraditional model. Hospitalization days per neurologic diagnosis were 0.4 days per patient-year for the traditional model, compared with 0.1 for the itinerant model.

There was a huge difference in costs. The traditional model’s charges were $14,650 per year, compared with only $1,850 for the itinerant model.

Physicians in the itinerant model also won out financially. With missed appointments and follow-ups, those in the traditional model lost $17,250 a year, compared with only $4,080 a year with the itinerant model.

Thus, the itinerant model delivered superior care, said Dr. Urion, who reported having no relevant disclosures.

NEW ORLEANS – Use of a variation on the traditional medical home model for pediatric neurology cases in an underserved population led to a decrease in hospitalizations and less frequent use of the emergency department in a study that compared outcomes and health care resource utilization between the two models.

The new model also led to faster referrals and fewer broken appointments, said Dr. David Urion, director of the learning disabilities and behavioral neurology program at Children’s Hospital in Boston, who led the study.

It is already well known that access to primary care is not as great for Americans who have a lower socioeconomic status, he said. The rate of access is even lower among non-English speakers, hovering around 70%, Dr. Urion said at the annual meeting of the American Academy of Neurology.

Access to specialists is generally lower than access to primary care.

In Boston, the Community Health Center movement has tried to improve access, in part by using a medical home model. Dr. Urion and his colleagues studied two different medical home models utilized by two centers – the South End Community Health Center and the Martha Eliot Community Health Center. Both are located in predominantly Hispanic and poorer areas.

One medical home model was what would be considered "traditional," in which patients were referred by the health center to a specialist at a hospital outpatient clinic. The other was an "itinerant" model, where the specialist would hold office hours at the center on a set day of the week. Patients were referred by a primary care physician.

From 2007 to 2011, the traditional model saw about 105 patients a year, while the itinerant model had about 103 patients a year. This was the equivalent of one session per week per provider, Dr. Urion said.

For the traditional model, the median time to an appointment was 90 days. The itinerant model cut that by 76 days to a wait of only 14 days for an appointment. Only 67% of new patients kept their appointment with the traditional model, compared with 95% of those in the nontraditional model. For existing patients, only 50% kept an appointment in the traditional model, compared with 85% of those in the newer model.

The use of the emergency department was reduced 18-fold, with 1.8 visits per patient-year for the traditional model and 0.1 per patient-year for the nontraditional model. Hospitalization days per neurologic diagnosis were 0.4 days per patient-year for the traditional model, compared with 0.1 for the itinerant model.

There was a huge difference in costs. The traditional model’s charges were $14,650 per year, compared with only $1,850 for the itinerant model.

Physicians in the itinerant model also won out financially. With missed appointments and follow-ups, those in the traditional model lost $17,250 a year, compared with only $4,080 a year with the itinerant model.

Thus, the itinerant model delivered superior care, said Dr. Urion, who reported having no relevant disclosures.

NEW ORLEANS – Pregabalin proved better than pramipexole for relieving restless legs syndrome, and it caused less symptom augmentation, in a yearlong trial funded by Pfizer, the manufacturer of pregabalin.

Dopamine agonists such as pramipexole (Mirapex) are first-line agents for restless legs syndrome (RLS), but over time they can actually make symptoms worse.

That’s a problem because "we are going to use these treatments for most of the patient’s life," lead investigator Dr. Diego Garcia-Borreguero, director of the Sleep Disorders Institute in Madrid, said at the annual meeting of the American Academy of Neurology.

His team compared 300 mg/day of pregabalin (Lyrica), a calcium-channel modulator, in 182 RLS patients against 0.25 mg/day of pramipexole in 178 patients; 0.5 mg/day of pramipexole in 180; and placebo in 179.

After 12 weeks, placebo patients were randomized to an active treatment arm, and the trial continued for another 40 weeks. The mean age of patients was 55 years and their mean RLS duration was 5 years; more than half were women.

At 12 weeks, pregabalin patients were doing 3.96 points better on the 40-point international RLS rating scale (IRLS) than were patients on 0.25 mg/day of pramipexole, and 1.69 points better than were patients on 0.5 mg/day of pramipexole. At the end of the year, pregabalin patients were doing 3.8 points better on the IRLS than were the 0.25-mg/day pramipexole patients, and 3.06 points better than the 0.5-mg pramipexole patients.

Also at the end of the year, the rate of augmentation was 2.1% in the pregabalin group, 5.3% in the 0.25 mg pramipexole group (P value for difference with pregabalin = .083), and 7.7% in the 0.5 mg pramipexole group (P value for difference with pregabalin = .012).

Dizziness, somnolence, and weight gain were more common with pregabalin, whereas with pramipexole nausea and headache were more common.

"Pregabalin is more effective than pramipexole" for RLS, Dr. Garcia-Borreguero concluded. "It has less augmentation over the long term, and it has superior efficacy."

Even so, Pfizer has stated it currently does not plan to seek approval for the indication from the Food and Drug Administration or regulators in other countries.

In the United States, the drug is indicated for neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, adjunctive therapy for adult patients with partial onset seizures, and fibromyalgia.

On May 4, the company halted a trial for neuropathic pain associated with HIV neuropathy after pregabalin proved no better than placebo.

Dr. Garcia-Borreguero has received personal compensation for activities with Pfizer, UCB Pharma, XenoPort, and Otsuka.

NEW ORLEANS – Pregabalin proved better than pramipexole for relieving restless legs syndrome, and it caused less symptom augmentation, in a yearlong trial funded by Pfizer, the manufacturer of pregabalin.

Dopamine agonists such as pramipexole (Mirapex) are first-line agents for restless legs syndrome (RLS), but over time they can actually make symptoms worse.

That’s a problem because "we are going to use these treatments for most of the patient’s life," lead investigator Dr. Diego Garcia-Borreguero, director of the Sleep Disorders Institute in Madrid, said at the annual meeting of the American Academy of Neurology.

His team compared 300 mg/day of pregabalin (Lyrica), a calcium-channel modulator, in 182 RLS patients against 0.25 mg/day of pramipexole in 178 patients; 0.5 mg/day of pramipexole in 180; and placebo in 179.

After 12 weeks, placebo patients were randomized to an active treatment arm, and the trial continued for another 40 weeks. The mean age of patients was 55 years and their mean RLS duration was 5 years; more than half were women.

At 12 weeks, pregabalin patients were doing 3.96 points better on the 40-point international RLS rating scale (IRLS) than were patients on 0.25 mg/day of pramipexole, and 1.69 points better than were patients on 0.5 mg/day of pramipexole. At the end of the year, pregabalin patients were doing 3.8 points better on the IRLS than were the 0.25-mg/day pramipexole patients, and 3.06 points better than the 0.5-mg pramipexole patients.

Also at the end of the year, the rate of augmentation was 2.1% in the pregabalin group, 5.3% in the 0.25 mg pramipexole group (P value for difference with pregabalin = .083), and 7.7% in the 0.5 mg pramipexole group (P value for difference with pregabalin = .012).

Dizziness, somnolence, and weight gain were more common with pregabalin, whereas with pramipexole nausea and headache were more common.

"Pregabalin is more effective than pramipexole" for RLS, Dr. Garcia-Borreguero concluded. "It has less augmentation over the long term, and it has superior efficacy."

Even so, Pfizer has stated it currently does not plan to seek approval for the indication from the Food and Drug Administration or regulators in other countries.

In the United States, the drug is indicated for neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, adjunctive therapy for adult patients with partial onset seizures, and fibromyalgia.

On May 4, the company halted a trial for neuropathic pain associated with HIV neuropathy after pregabalin proved no better than placebo.

Dr. Garcia-Borreguero has received personal compensation for activities with Pfizer, UCB Pharma, XenoPort, and Otsuka.

NEW ORLEANS – Pregabalin proved better than pramipexole for relieving restless legs syndrome, and it caused less symptom augmentation, in a yearlong trial funded by Pfizer, the manufacturer of pregabalin.

Dopamine agonists such as pramipexole (Mirapex) are first-line agents for restless legs syndrome (RLS), but over time they can actually make symptoms worse.

That’s a problem because "we are going to use these treatments for most of the patient’s life," lead investigator Dr. Diego Garcia-Borreguero, director of the Sleep Disorders Institute in Madrid, said at the annual meeting of the American Academy of Neurology.

His team compared 300 mg/day of pregabalin (Lyrica), a calcium-channel modulator, in 182 RLS patients against 0.25 mg/day of pramipexole in 178 patients; 0.5 mg/day of pramipexole in 180; and placebo in 179.

After 12 weeks, placebo patients were randomized to an active treatment arm, and the trial continued for another 40 weeks. The mean age of patients was 55 years and their mean RLS duration was 5 years; more than half were women.

At 12 weeks, pregabalin patients were doing 3.96 points better on the 40-point international RLS rating scale (IRLS) than were patients on 0.25 mg/day of pramipexole, and 1.69 points better than were patients on 0.5 mg/day of pramipexole. At the end of the year, pregabalin patients were doing 3.8 points better on the IRLS than were the 0.25-mg/day pramipexole patients, and 3.06 points better than the 0.5-mg pramipexole patients.

Also at the end of the year, the rate of augmentation was 2.1% in the pregabalin group, 5.3% in the 0.25 mg pramipexole group (P value for difference with pregabalin = .083), and 7.7% in the 0.5 mg pramipexole group (P value for difference with pregabalin = .012).

Dizziness, somnolence, and weight gain were more common with pregabalin, whereas with pramipexole nausea and headache were more common.

"Pregabalin is more effective than pramipexole" for RLS, Dr. Garcia-Borreguero concluded. "It has less augmentation over the long term, and it has superior efficacy."

Even so, Pfizer has stated it currently does not plan to seek approval for the indication from the Food and Drug Administration or regulators in other countries.

In the United States, the drug is indicated for neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, adjunctive therapy for adult patients with partial onset seizures, and fibromyalgia.

On May 4, the company halted a trial for neuropathic pain associated with HIV neuropathy after pregabalin proved no better than placebo.

Dr. Garcia-Borreguero has received personal compensation for activities with Pfizer, UCB Pharma, XenoPort, and Otsuka.

NEW ORLEANS – There should be no hesitation to use rituximab or cyclophosphamide in anti–N-methyl-d-aspartate receptor encephalitis patients who do not respond to steroids, immunoglobulins, or plasma exchange within the first 4 weeks, according to neurologist Maarten Titulaer, the lead investigator on a 467-patient study of the disease.

"Treat aggressively. The quicker you treat, the better the outcome. If first-line therapy fails, progress to second-line treatment," said Dr. Titulaer, a visiting research fellow at the University of Pennsylvania, Philadelphia.

Rituximab (Rituxan) and cyclophosphamide made relapse less likely. "The chance is only 5% that [patients] will relapse in the first 2 years" if they received either drug. "It was 20% in patients treated only with, for example, steroids or [intravenous immunoglobulin]," he said at the annual meeting of the American Academy of Neurology.

Dr. Titulaer’s team tracked 2-year outcomes in the patients. Just over half responded to first-line treatment within 4 weeks. Of those, 98% were back home and independent in daily activities within 2 years; 90% had returned to school or work.

Just under half, however, did not respond to first-line agents; just over half of those went on to either rituximab or cyclophosphamide. Of those, 55% recovered fully within 2 years, 76% were back home and independent in daily activities, and about 20% had died or were in a vegetative state.

Of those who did not get rituximab or cyclophosphamide after failing first-line treatments but who instead got another round of those treatments or no further treatment, 37% were fully recovered at 2 years; 55% were back home and independent in daily activities; and 33% had died or were in a vegetative state. The differences in response between the groups after they failed first-line therapies were statistically significant.

In a group of approximately 25 patients who were not treated at all because the diagnosis was missed (or for some other reason), 38% were dead or in a vegetative state after 2 years.

First identified in 2007, N-methyl-d-aspartate (NMDA) receptor encephalitis predominately attacks young women and is associated with ovarian teratomas. The disease is thought to be caused by an autoantibody attack on subunits of brain NMDA glutamate receptors, which are believed to control synaptic plasticity and memory function (N. Engl. J. Med. 2009;361:302-3).

In all, 81% of the cases were female; their median age was 19 years (range, 1-85 years). In patients younger than 12 years and older than 45 years of age, incidence split more evenly between sexes. A tumor occurred in 39% of patients, and almost all were teratomas. An ovarian teratoma occurred in 54% of females older than 12 years, compared with only 4% of girls younger than 12. Patients with tumors had slightly more severe disease.

Immunotherapy plus tumor removal, when appropriate, resulted in full recovery or substantial improvement in about two-thirds of patients by 8 months, and in 77% at 2 years. Relapses occurred in 14% of patients, about three-quarters of them without teratomas.

As currently understood, the disease has protean manifestations, including cognitive problems, psychiatric issues, seizures, dyskinesias, decreased consciousness, behavioral changes, autonomic instability, hypoventilation, movement disorders, and memory and speech disorders.

Almost all of the patients in the study presented with three or more of those symptoms. Adults tended to present with behavioral changes and memory problems; children tended to present with seizures, movement disorders, and – less commonly – abnormal behavior. Within the first month, memory problems and hypoventilation were more common in adults; movement disorders and ataxia were more frequent in children.

Dr. Titulaer said that he had no disclosures.

NEW ORLEANS – There should be no hesitation to use rituximab or cyclophosphamide in anti–N-methyl-d-aspartate receptor encephalitis patients who do not respond to steroids, immunoglobulins, or plasma exchange within the first 4 weeks, according to neurologist Maarten Titulaer, the lead investigator on a 467-patient study of the disease.

"Treat aggressively. The quicker you treat, the better the outcome. If first-line therapy fails, progress to second-line treatment," said Dr. Titulaer, a visiting research fellow at the University of Pennsylvania, Philadelphia.

Rituximab (Rituxan) and cyclophosphamide made relapse less likely. "The chance is only 5% that [patients] will relapse in the first 2 years" if they received either drug. "It was 20% in patients treated only with, for example, steroids or [intravenous immunoglobulin]," he said at the annual meeting of the American Academy of Neurology.

Dr. Titulaer’s team tracked 2-year outcomes in the patients. Just over half responded to first-line treatment within 4 weeks. Of those, 98% were back home and independent in daily activities within 2 years; 90% had returned to school or work.

Just under half, however, did not respond to first-line agents; just over half of those went on to either rituximab or cyclophosphamide. Of those, 55% recovered fully within 2 years, 76% were back home and independent in daily activities, and about 20% had died or were in a vegetative state.

Of those who did not get rituximab or cyclophosphamide after failing first-line treatments but who instead got another round of those treatments or no further treatment, 37% were fully recovered at 2 years; 55% were back home and independent in daily activities; and 33% had died or were in a vegetative state. The differences in response between the groups after they failed first-line therapies were statistically significant.

In a group of approximately 25 patients who were not treated at all because the diagnosis was missed (or for some other reason), 38% were dead or in a vegetative state after 2 years.

First identified in 2007, N-methyl-d-aspartate (NMDA) receptor encephalitis predominately attacks young women and is associated with ovarian teratomas. The disease is thought to be caused by an autoantibody attack on subunits of brain NMDA glutamate receptors, which are believed to control synaptic plasticity and memory function (N. Engl. J. Med. 2009;361:302-3).

In all, 81% of the cases were female; their median age was 19 years (range, 1-85 years). In patients younger than 12 years and older than 45 years of age, incidence split more evenly between sexes. A tumor occurred in 39% of patients, and almost all were teratomas. An ovarian teratoma occurred in 54% of females older than 12 years, compared with only 4% of girls younger than 12. Patients with tumors had slightly more severe disease.

Immunotherapy plus tumor removal, when appropriate, resulted in full recovery or substantial improvement in about two-thirds of patients by 8 months, and in 77% at 2 years. Relapses occurred in 14% of patients, about three-quarters of them without teratomas.

As currently understood, the disease has protean manifestations, including cognitive problems, psychiatric issues, seizures, dyskinesias, decreased consciousness, behavioral changes, autonomic instability, hypoventilation, movement disorders, and memory and speech disorders.

Almost all of the patients in the study presented with three or more of those symptoms. Adults tended to present with behavioral changes and memory problems; children tended to present with seizures, movement disorders, and – less commonly – abnormal behavior. Within the first month, memory problems and hypoventilation were more common in adults; movement disorders and ataxia were more frequent in children.

Dr. Titulaer said that he had no disclosures.

NEW ORLEANS – There should be no hesitation to use rituximab or cyclophosphamide in anti–N-methyl-d-aspartate receptor encephalitis patients who do not respond to steroids, immunoglobulins, or plasma exchange within the first 4 weeks, according to neurologist Maarten Titulaer, the lead investigator on a 467-patient study of the disease.

"Treat aggressively. The quicker you treat, the better the outcome. If first-line therapy fails, progress to second-line treatment," said Dr. Titulaer, a visiting research fellow at the University of Pennsylvania, Philadelphia.

Rituximab (Rituxan) and cyclophosphamide made relapse less likely. "The chance is only 5% that [patients] will relapse in the first 2 years" if they received either drug. "It was 20% in patients treated only with, for example, steroids or [intravenous immunoglobulin]," he said at the annual meeting of the American Academy of Neurology.

Dr. Titulaer’s team tracked 2-year outcomes in the patients. Just over half responded to first-line treatment within 4 weeks. Of those, 98% were back home and independent in daily activities within 2 years; 90% had returned to school or work.

Just under half, however, did not respond to first-line agents; just over half of those went on to either rituximab or cyclophosphamide. Of those, 55% recovered fully within 2 years, 76% were back home and independent in daily activities, and about 20% had died or were in a vegetative state.

Of those who did not get rituximab or cyclophosphamide after failing first-line treatments but who instead got another round of those treatments or no further treatment, 37% were fully recovered at 2 years; 55% were back home and independent in daily activities; and 33% had died or were in a vegetative state. The differences in response between the groups after they failed first-line therapies were statistically significant.

In a group of approximately 25 patients who were not treated at all because the diagnosis was missed (or for some other reason), 38% were dead or in a vegetative state after 2 years.

First identified in 2007, N-methyl-d-aspartate (NMDA) receptor encephalitis predominately attacks young women and is associated with ovarian teratomas. The disease is thought to be caused by an autoantibody attack on subunits of brain NMDA glutamate receptors, which are believed to control synaptic plasticity and memory function (N. Engl. J. Med. 2009;361:302-3).

In all, 81% of the cases were female; their median age was 19 years (range, 1-85 years). In patients younger than 12 years and older than 45 years of age, incidence split more evenly between sexes. A tumor occurred in 39% of patients, and almost all were teratomas. An ovarian teratoma occurred in 54% of females older than 12 years, compared with only 4% of girls younger than 12. Patients with tumors had slightly more severe disease.

Immunotherapy plus tumor removal, when appropriate, resulted in full recovery or substantial improvement in about two-thirds of patients by 8 months, and in 77% at 2 years. Relapses occurred in 14% of patients, about three-quarters of them without teratomas.

As currently understood, the disease has protean manifestations, including cognitive problems, psychiatric issues, seizures, dyskinesias, decreased consciousness, behavioral changes, autonomic instability, hypoventilation, movement disorders, and memory and speech disorders.

Almost all of the patients in the study presented with three or more of those symptoms. Adults tended to present with behavioral changes and memory problems; children tended to present with seizures, movement disorders, and – less commonly – abnormal behavior. Within the first month, memory problems and hypoventilation were more common in adults; movement disorders and ataxia were more frequent in children.

Dr. Titulaer said that he had no disclosures.

NEW ORLEANS – Dopamine agonist–induced impulse control disorders may be more likely in Parkinson’s disease patients who smoke, drink, or consume caffeine, according to the first prospective cohort study of the problem.

"We found a number of interesting things" when the 18 patients (39%) in the study who developed an impulse control disorder (ICD) were compared with the 28 who did not, said lead author Jesse Bastiaens, a medical student at Cornell University, New York.

The 18 had a higher baseline prevalence of caffeine use (100% vs. 67%; P = .007), lifetime prevalence of cigarette smoking (44% vs. 14%; P = .04), and cumulative exposure to both caffeine (72 vs. 38 cup-years; P = .04) and cigarettes (median 2 vs. 0 pack-years; P = .07). There was also a nonsignificant trend towards a higher baseline prevalence of alcohol use.

At baseline, ICD patients also had a greater prevalence of motor complications (61% vs. 25%; P = .01) and lower baseline modified Hoehn and Yahr Scale scores (mean 1.6 vs. 1.9; P = .05), despite comparable total Parkinson’s disease (PD) drug use in both groups (median, 150 levodopa equivalents in both groups).

ICD patients had higher peak-dopamine agonist (DA) doses (median, 300 vs. 165 levodopa equivalents; P = .03) but no significant differences in DA treatment duration or cumulative exposure.

"The risk of ICDs in PD is related to both patient-specific factors and peak DA dosage. Attention to these susceptibility factors may help to reduce the incidence of ICDs in PD," Mr. Bastiaens said at the annual meeting of the American Academy of Neurology.

Besides counseling patients about the risk, "you might be less eager to use a dopamine agonists or use lower doses in people with prior histories of smoking or heavy drinking or other addictive behaviors," said Dr. Ronald Pfeiffer, vice chair of the department of neurology at the University of Tennessee, Memphis, who moderated Mr. Bastiaens’ presentation.

Patients who developed an impulse disorder did so after a mean treatment duration of 23 months (range, 3-114 months). Age, age of PD onset, sex, depression, anxiety, and other factors were not predictive.

None of the 46 patients (all outpatients) had previous histories of ICDs, and none were demented. Their mean age was 62 years, and about half were women. ICD was diagnosed by semistructured interviews and clinical data, with criteria that were perhaps a bit less strict than were those in the DSM-IV, according to Mr. Bastiaens, who said that the researchers thought that casting a slightly wider net might be useful.

There was 1 case per 100 person-months of DA exposure. "We found that impulse control disorders can really occur at anytime during dopamine agonist therapy – as early as 3 months or 9 or more years," said Mr. Bastiaens, who noted that a questionnaire to assess for ICDs in Parkinson’s patients has been recently validated (Mov. Disord. 2012;27:242-7).

A 2010 cross-sectional study in 3,090 Parkinson’s patients found an association between ICDs and current cigarette smoking and family histories of gambling problems, among other factors. It did not find an association with DA dosage. Just over 17% of patients on the drugs developed ICDs (Arch. Neurol. 2010;67:589-95).

The study was supported by the Parkinson’s Disease Foundation. Mr. Bastiaens said that he had nothing to disclose. Dr. Pfeiffer reported personal compensation from several pharmaceutical companies, none of which were involved in the study.

NEW ORLEANS – Dopamine agonist–induced impulse control disorders may be more likely in Parkinson’s disease patients who smoke, drink, or consume caffeine, according to the first prospective cohort study of the problem.

"We found a number of interesting things" when the 18 patients (39%) in the study who developed an impulse control disorder (ICD) were compared with the 28 who did not, said lead author Jesse Bastiaens, a medical student at Cornell University, New York.

The 18 had a higher baseline prevalence of caffeine use (100% vs. 67%; P = .007), lifetime prevalence of cigarette smoking (44% vs. 14%; P = .04), and cumulative exposure to both caffeine (72 vs. 38 cup-years; P = .04) and cigarettes (median 2 vs. 0 pack-years; P = .07). There was also a nonsignificant trend towards a higher baseline prevalence of alcohol use.

At baseline, ICD patients also had a greater prevalence of motor complications (61% vs. 25%; P = .01) and lower baseline modified Hoehn and Yahr Scale scores (mean 1.6 vs. 1.9; P = .05), despite comparable total Parkinson’s disease (PD) drug use in both groups (median, 150 levodopa equivalents in both groups).

ICD patients had higher peak-dopamine agonist (DA) doses (median, 300 vs. 165 levodopa equivalents; P = .03) but no significant differences in DA treatment duration or cumulative exposure.

"The risk of ICDs in PD is related to both patient-specific factors and peak DA dosage. Attention to these susceptibility factors may help to reduce the incidence of ICDs in PD," Mr. Bastiaens said at the annual meeting of the American Academy of Neurology.

Besides counseling patients about the risk, "you might be less eager to use a dopamine agonists or use lower doses in people with prior histories of smoking or heavy drinking or other addictive behaviors," said Dr. Ronald Pfeiffer, vice chair of the department of neurology at the University of Tennessee, Memphis, who moderated Mr. Bastiaens’ presentation.

Patients who developed an impulse disorder did so after a mean treatment duration of 23 months (range, 3-114 months). Age, age of PD onset, sex, depression, anxiety, and other factors were not predictive.

None of the 46 patients (all outpatients) had previous histories of ICDs, and none were demented. Their mean age was 62 years, and about half were women. ICD was diagnosed by semistructured interviews and clinical data, with criteria that were perhaps a bit less strict than were those in the DSM-IV, according to Mr. Bastiaens, who said that the researchers thought that casting a slightly wider net might be useful.

There was 1 case per 100 person-months of DA exposure. "We found that impulse control disorders can really occur at anytime during dopamine agonist therapy – as early as 3 months or 9 or more years," said Mr. Bastiaens, who noted that a questionnaire to assess for ICDs in Parkinson’s patients has been recently validated (Mov. Disord. 2012;27:242-7).

A 2010 cross-sectional study in 3,090 Parkinson’s patients found an association between ICDs and current cigarette smoking and family histories of gambling problems, among other factors. It did not find an association with DA dosage. Just over 17% of patients on the drugs developed ICDs (Arch. Neurol. 2010;67:589-95).

The study was supported by the Parkinson’s Disease Foundation. Mr. Bastiaens said that he had nothing to disclose. Dr. Pfeiffer reported personal compensation from several pharmaceutical companies, none of which were involved in the study.

NEW ORLEANS – Dopamine agonist–induced impulse control disorders may be more likely in Parkinson’s disease patients who smoke, drink, or consume caffeine, according to the first prospective cohort study of the problem.

"We found a number of interesting things" when the 18 patients (39%) in the study who developed an impulse control disorder (ICD) were compared with the 28 who did not, said lead author Jesse Bastiaens, a medical student at Cornell University, New York.

The 18 had a higher baseline prevalence of caffeine use (100% vs. 67%; P = .007), lifetime prevalence of cigarette smoking (44% vs. 14%; P = .04), and cumulative exposure to both caffeine (72 vs. 38 cup-years; P = .04) and cigarettes (median 2 vs. 0 pack-years; P = .07). There was also a nonsignificant trend towards a higher baseline prevalence of alcohol use.

At baseline, ICD patients also had a greater prevalence of motor complications (61% vs. 25%; P = .01) and lower baseline modified Hoehn and Yahr Scale scores (mean 1.6 vs. 1.9; P = .05), despite comparable total Parkinson’s disease (PD) drug use in both groups (median, 150 levodopa equivalents in both groups).

ICD patients had higher peak-dopamine agonist (DA) doses (median, 300 vs. 165 levodopa equivalents; P = .03) but no significant differences in DA treatment duration or cumulative exposure.

"The risk of ICDs in PD is related to both patient-specific factors and peak DA dosage. Attention to these susceptibility factors may help to reduce the incidence of ICDs in PD," Mr. Bastiaens said at the annual meeting of the American Academy of Neurology.

Besides counseling patients about the risk, "you might be less eager to use a dopamine agonists or use lower doses in people with prior histories of smoking or heavy drinking or other addictive behaviors," said Dr. Ronald Pfeiffer, vice chair of the department of neurology at the University of Tennessee, Memphis, who moderated Mr. Bastiaens’ presentation.

Patients who developed an impulse disorder did so after a mean treatment duration of 23 months (range, 3-114 months). Age, age of PD onset, sex, depression, anxiety, and other factors were not predictive.

None of the 46 patients (all outpatients) had previous histories of ICDs, and none were demented. Their mean age was 62 years, and about half were women. ICD was diagnosed by semistructured interviews and clinical data, with criteria that were perhaps a bit less strict than were those in the DSM-IV, according to Mr. Bastiaens, who said that the researchers thought that casting a slightly wider net might be useful.

There was 1 case per 100 person-months of DA exposure. "We found that impulse control disorders can really occur at anytime during dopamine agonist therapy – as early as 3 months or 9 or more years," said Mr. Bastiaens, who noted that a questionnaire to assess for ICDs in Parkinson’s patients has been recently validated (Mov. Disord. 2012;27:242-7).

A 2010 cross-sectional study in 3,090 Parkinson’s patients found an association between ICDs and current cigarette smoking and family histories of gambling problems, among other factors. It did not find an association with DA dosage. Just over 17% of patients on the drugs developed ICDs (Arch. Neurol. 2010;67:589-95).

The study was supported by the Parkinson’s Disease Foundation. Mr. Bastiaens said that he had nothing to disclose. Dr. Pfeiffer reported personal compensation from several pharmaceutical companies, none of which were involved in the study.

NEW ORLEANS – A reformulated version of the previously withdrawn Neupro rotigotine patch had favorable results in separate studies of patients with advanced idiopathic Parkinson’s disease and restless legs syndrome, according to reports given prior to the planned return of the patch to the U.S. market in July.

The dopamine agonist patch was originally approved by the Food and Drug Administration in 2007 for early-stage idiopathic Parkinson’s disease, but UCB Pharma withdrew it from the U.S. market in 2008 because rotigotine was crystallizing out of the delivery matrix. The agency approved a reformulated version in April along with revised labeling that now indicates Neupro for all stages of idiopathic Parkinson’s, plus moderate to severe primary restless legs syndrome (RLS).

The return of the patch is "terrific news for the Parkinson’s disease community. ... Because Parkinson’s disease patients typically have to take many doses of medications each day, the re-approval of the patch will hopefully help a lot of sufferers," by cutting pill burden, among other things, said Dr. Michael Okun, medical director of the National Parkinson Foundation, in a written statement.

In a 16-week, randomized trial involving 514 advanced idiopathic Parkinson’s disease (PD) patients, 8 mg/24 hours reduced off-time by 2.4 hours per day after 12 weeks of maintenance therapy, a statistically significant benefit over placebo, which reduced off-time by 1.5 hours. Lower patch doses reduced off-time as well, but not significantly better than did placebo. All patients in the trial were on levodopa; other medications were allowed. Off-time was assessed by home diaries.

The benefit of 8 mg/24 hour is in line with the new label, which recommends that dosage for advanced Parkinson’s, and 6 mg/24 hours for early-stage disease. The recommended RLS dosage is up to 3 mg/24 hours.

The label details two clinical trials for RLS. In one involving 505 patients, scores on the 40-point IRLS (International RLS) rating scale improved by 14.2 points in patients who were randomized to 3 mg/24 hours for 6 months, whereas placebo improved scores by 9 points. That difference was statistically significant, as were lower Neupro doses. UCB fleshed out the results at the annual meeting of the American Academy of Neurology, noting the magnitude of statistically significant improvements, compared with placebo, in individual components of the IRLS, such as sleep disturbances (0.4-point improvement over placebo on a 5-point scale), impact on daily activities (0.3-point improvement over placebo on a 5-point scale), and frequency of symptoms (0.9-point improvement over placebo on a 5-point scale).

The company also presented post hoc analyses of previous trials that showed that Neupro may help fatigue, apathy, anhedonia, anxiety, and depression in PD. Another post hoc analysis of a 287-patient trial suggested that it might also help with pain; PD patients with a score equal to 1 (any pain) on a 10-point Likert pain scale had a 0.54-point improvement over placebo after being maintained at 2-16 mg/24 hours for 4 weeks.

The patch’s new labeling adds advice on discontinuing the drug, as well as information about the risk of augmentation and rebound in RLS, plus additional detail on somnolence, hypotension, hallucination, impulse control disorder, and other possible side effects.

In the recent randomized trial of 514 patients with PD, "the most common adverse events included application site reactions [15% vs. 7% placebo], nausea [12% vs. 7% placebo], and dyskinesias [8% vs. 3% placebo]. The remainder of the safety profile was similar to previous studies of rotigotine in patients with advanced Parkinson’s," said Dr. Lawrence Elmer, medical director of the center for neurological disorders at the University of Toledo (Ohio), who presented the findings at the meeting.

Dr. Elmer disclosed unrestricted educational grants and payments for consulting, advisory, and speaking services from UCB Pharma and other pharmaceutical companies. Dr. Okun had no current, relevant disclosures.

NEW ORLEANS – A reformulated version of the previously withdrawn Neupro rotigotine patch had favorable results in separate studies of patients with advanced idiopathic Parkinson’s disease and restless legs syndrome, according to reports given prior to the planned return of the patch to the U.S. market in July.

The dopamine agonist patch was originally approved by the Food and Drug Administration in 2007 for early-stage idiopathic Parkinson’s disease, but UCB Pharma withdrew it from the U.S. market in 2008 because rotigotine was crystallizing out of the delivery matrix. The agency approved a reformulated version in April along with revised labeling that now indicates Neupro for all stages of idiopathic Parkinson’s, plus moderate to severe primary restless legs syndrome (RLS).

The return of the patch is "terrific news for the Parkinson’s disease community. ... Because Parkinson’s disease patients typically have to take many doses of medications each day, the re-approval of the patch will hopefully help a lot of sufferers," by cutting pill burden, among other things, said Dr. Michael Okun, medical director of the National Parkinson Foundation, in a written statement.

In a 16-week, randomized trial involving 514 advanced idiopathic Parkinson’s disease (PD) patients, 8 mg/24 hours reduced off-time by 2.4 hours per day after 12 weeks of maintenance therapy, a statistically significant benefit over placebo, which reduced off-time by 1.5 hours. Lower patch doses reduced off-time as well, but not significantly better than did placebo. All patients in the trial were on levodopa; other medications were allowed. Off-time was assessed by home diaries.

The benefit of 8 mg/24 hour is in line with the new label, which recommends that dosage for advanced Parkinson’s, and 6 mg/24 hours for early-stage disease. The recommended RLS dosage is up to 3 mg/24 hours.

The label details two clinical trials for RLS. In one involving 505 patients, scores on the 40-point IRLS (International RLS) rating scale improved by 14.2 points in patients who were randomized to 3 mg/24 hours for 6 months, whereas placebo improved scores by 9 points. That difference was statistically significant, as were lower Neupro doses. UCB fleshed out the results at the annual meeting of the American Academy of Neurology, noting the magnitude of statistically significant improvements, compared with placebo, in individual components of the IRLS, such as sleep disturbances (0.4-point improvement over placebo on a 5-point scale), impact on daily activities (0.3-point improvement over placebo on a 5-point scale), and frequency of symptoms (0.9-point improvement over placebo on a 5-point scale).

The company also presented post hoc analyses of previous trials that showed that Neupro may help fatigue, apathy, anhedonia, anxiety, and depression in PD. Another post hoc analysis of a 287-patient trial suggested that it might also help with pain; PD patients with a score equal to 1 (any pain) on a 10-point Likert pain scale had a 0.54-point improvement over placebo after being maintained at 2-16 mg/24 hours for 4 weeks.

The patch’s new labeling adds advice on discontinuing the drug, as well as information about the risk of augmentation and rebound in RLS, plus additional detail on somnolence, hypotension, hallucination, impulse control disorder, and other possible side effects.

In the recent randomized trial of 514 patients with PD, "the most common adverse events included application site reactions [15% vs. 7% placebo], nausea [12% vs. 7% placebo], and dyskinesias [8% vs. 3% placebo]. The remainder of the safety profile was similar to previous studies of rotigotine in patients with advanced Parkinson’s," said Dr. Lawrence Elmer, medical director of the center for neurological disorders at the University of Toledo (Ohio), who presented the findings at the meeting.

Dr. Elmer disclosed unrestricted educational grants and payments for consulting, advisory, and speaking services from UCB Pharma and other pharmaceutical companies. Dr. Okun had no current, relevant disclosures.

NEW ORLEANS – A reformulated version of the previously withdrawn Neupro rotigotine patch had favorable results in separate studies of patients with advanced idiopathic Parkinson’s disease and restless legs syndrome, according to reports given prior to the planned return of the patch to the U.S. market in July.

The dopamine agonist patch was originally approved by the Food and Drug Administration in 2007 for early-stage idiopathic Parkinson’s disease, but UCB Pharma withdrew it from the U.S. market in 2008 because rotigotine was crystallizing out of the delivery matrix. The agency approved a reformulated version in April along with revised labeling that now indicates Neupro for all stages of idiopathic Parkinson’s, plus moderate to severe primary restless legs syndrome (RLS).

The return of the patch is "terrific news for the Parkinson’s disease community. ... Because Parkinson’s disease patients typically have to take many doses of medications each day, the re-approval of the patch will hopefully help a lot of sufferers," by cutting pill burden, among other things, said Dr. Michael Okun, medical director of the National Parkinson Foundation, in a written statement.

In a 16-week, randomized trial involving 514 advanced idiopathic Parkinson’s disease (PD) patients, 8 mg/24 hours reduced off-time by 2.4 hours per day after 12 weeks of maintenance therapy, a statistically significant benefit over placebo, which reduced off-time by 1.5 hours. Lower patch doses reduced off-time as well, but not significantly better than did placebo. All patients in the trial were on levodopa; other medications were allowed. Off-time was assessed by home diaries.

The benefit of 8 mg/24 hour is in line with the new label, which recommends that dosage for advanced Parkinson’s, and 6 mg/24 hours for early-stage disease. The recommended RLS dosage is up to 3 mg/24 hours.

The label details two clinical trials for RLS. In one involving 505 patients, scores on the 40-point IRLS (International RLS) rating scale improved by 14.2 points in patients who were randomized to 3 mg/24 hours for 6 months, whereas placebo improved scores by 9 points. That difference was statistically significant, as were lower Neupro doses. UCB fleshed out the results at the annual meeting of the American Academy of Neurology, noting the magnitude of statistically significant improvements, compared with placebo, in individual components of the IRLS, such as sleep disturbances (0.4-point improvement over placebo on a 5-point scale), impact on daily activities (0.3-point improvement over placebo on a 5-point scale), and frequency of symptoms (0.9-point improvement over placebo on a 5-point scale).

The company also presented post hoc analyses of previous trials that showed that Neupro may help fatigue, apathy, anhedonia, anxiety, and depression in PD. Another post hoc analysis of a 287-patient trial suggested that it might also help with pain; PD patients with a score equal to 1 (any pain) on a 10-point Likert pain scale had a 0.54-point improvement over placebo after being maintained at 2-16 mg/24 hours for 4 weeks.

The patch’s new labeling adds advice on discontinuing the drug, as well as information about the risk of augmentation and rebound in RLS, plus additional detail on somnolence, hypotension, hallucination, impulse control disorder, and other possible side effects.

In the recent randomized trial of 514 patients with PD, "the most common adverse events included application site reactions [15% vs. 7% placebo], nausea [12% vs. 7% placebo], and dyskinesias [8% vs. 3% placebo]. The remainder of the safety profile was similar to previous studies of rotigotine in patients with advanced Parkinson’s," said Dr. Lawrence Elmer, medical director of the center for neurological disorders at the University of Toledo (Ohio), who presented the findings at the meeting.

Dr. Elmer disclosed unrestricted educational grants and payments for consulting, advisory, and speaking services from UCB Pharma and other pharmaceutical companies. Dr. Okun had no current, relevant disclosures.

NEW ORLEANS – The incidence of hospitalizations for status epilepticus rose nearly fourfold during 1980-2009, according to researchers who analyzed the National Center for Health Statistics’ National Hospital Database Survey.

The population-adjusted incidence increased from 3.7/100,000 to 14.2/100,000, although the median hospital length of stay for status epilepticus (SE) remained relatively stable at a median of 4-5 days. Hospitalizations for SE also tended to follow a bimodal distribution with the greatest incidence in the first decade of life and between the 5th and 6th decades.

The data on the epidemiology of SE are "quite limited" and come mainly from small, population-based studies, which often do not have findings that are generalizable to the U.S. population and do not provide temporal trends, said Dr. Bhavpreet Dham of the University of Medicine and Dentistry of New Jersey, Camden.

Dr. Dham also noted that it is estimated that $4 billion is spent each year in the United States on status epilepticus hospitalizations, which is even more than is spent on myocardial infarctions or heart failure (Seizure 2005;14:46-51).

He and his colleagues analyzed 699,690 patient discharges in the study’s 30-year time span. These hospitalizations accounted for just 0.07% of about 1 billion hospitalizations in the database. The database covers hospitals in all 50 states and the District of Columbia and uses abstracted ICD-9 codes for diagnoses.

"We believe that this is one of the largest epidemiological studies of SE," Dr. Dham said.

In most of the years, the incidence of SE was about 10% higher in men than in women, and nonwhite patients also had a higher incidence than did whites.

In-hospital mortality (about 8.4% overall) did not differ between the sexes. Although mortality was lowest among patients aged 10 years or younger (2.7%) and highest among those older than 80 years (19%), the incidence of hospitalizations was lowest for patients in the first decade of life and highest in those older than 80 years.

These changes may be the result of a temporal shift in population age distribution during the past 30 years because of more adults living to an older age than there were 30 years ago. In recent years more people have been diagnosed with SE, Dr. Dham noted.

He said that the study is limited by the investigators’ inability to audit the database to review patient charts and the lack of morbidity and mortality data for patients once they left the hospital. Furthermore, the investigators could not differentiate between convulsive, nonconvulsive, and refractory SE because the ICD-9 coding does not allow it.

Dr. Dham said that he had no relevant financial disclosures.

NEW ORLEANS – The incidence of hospitalizations for status epilepticus rose nearly fourfold during 1980-2009, according to researchers who analyzed the National Center for Health Statistics’ National Hospital Database Survey.

The population-adjusted incidence increased from 3.7/100,000 to 14.2/100,000, although the median hospital length of stay for status epilepticus (SE) remained relatively stable at a median of 4-5 days. Hospitalizations for SE also tended to follow a bimodal distribution with the greatest incidence in the first decade of life and between the 5th and 6th decades.

The data on the epidemiology of SE are "quite limited" and come mainly from small, population-based studies, which often do not have findings that are generalizable to the U.S. population and do not provide temporal trends, said Dr. Bhavpreet Dham of the University of Medicine and Dentistry of New Jersey, Camden.

Dr. Dham also noted that it is estimated that $4 billion is spent each year in the United States on status epilepticus hospitalizations, which is even more than is spent on myocardial infarctions or heart failure (Seizure 2005;14:46-51).

He and his colleagues analyzed 699,690 patient discharges in the study’s 30-year time span. These hospitalizations accounted for just 0.07% of about 1 billion hospitalizations in the database. The database covers hospitals in all 50 states and the District of Columbia and uses abstracted ICD-9 codes for diagnoses.

"We believe that this is one of the largest epidemiological studies of SE," Dr. Dham said.

In most of the years, the incidence of SE was about 10% higher in men than in women, and nonwhite patients also had a higher incidence than did whites.

In-hospital mortality (about 8.4% overall) did not differ between the sexes. Although mortality was lowest among patients aged 10 years or younger (2.7%) and highest among those older than 80 years (19%), the incidence of hospitalizations was lowest for patients in the first decade of life and highest in those older than 80 years.

These changes may be the result of a temporal shift in population age distribution during the past 30 years because of more adults living to an older age than there were 30 years ago. In recent years more people have been diagnosed with SE, Dr. Dham noted.

He said that the study is limited by the investigators’ inability to audit the database to review patient charts and the lack of morbidity and mortality data for patients once they left the hospital. Furthermore, the investigators could not differentiate between convulsive, nonconvulsive, and refractory SE because the ICD-9 coding does not allow it.

Dr. Dham said that he had no relevant financial disclosures.

NEW ORLEANS – The incidence of hospitalizations for status epilepticus rose nearly fourfold during 1980-2009, according to researchers who analyzed the National Center for Health Statistics’ National Hospital Database Survey.

The population-adjusted incidence increased from 3.7/100,000 to 14.2/100,000, although the median hospital length of stay for status epilepticus (SE) remained relatively stable at a median of 4-5 days. Hospitalizations for SE also tended to follow a bimodal distribution with the greatest incidence in the first decade of life and between the 5th and 6th decades.

The data on the epidemiology of SE are "quite limited" and come mainly from small, population-based studies, which often do not have findings that are generalizable to the U.S. population and do not provide temporal trends, said Dr. Bhavpreet Dham of the University of Medicine and Dentistry of New Jersey, Camden.

Dr. Dham also noted that it is estimated that $4 billion is spent each year in the United States on status epilepticus hospitalizations, which is even more than is spent on myocardial infarctions or heart failure (Seizure 2005;14:46-51).

He and his colleagues analyzed 699,690 patient discharges in the study’s 30-year time span. These hospitalizations accounted for just 0.07% of about 1 billion hospitalizations in the database. The database covers hospitals in all 50 states and the District of Columbia and uses abstracted ICD-9 codes for diagnoses.

"We believe that this is one of the largest epidemiological studies of SE," Dr. Dham said.

In most of the years, the incidence of SE was about 10% higher in men than in women, and nonwhite patients also had a higher incidence than did whites.

In-hospital mortality (about 8.4% overall) did not differ between the sexes. Although mortality was lowest among patients aged 10 years or younger (2.7%) and highest among those older than 80 years (19%), the incidence of hospitalizations was lowest for patients in the first decade of life and highest in those older than 80 years.

These changes may be the result of a temporal shift in population age distribution during the past 30 years because of more adults living to an older age than there were 30 years ago. In recent years more people have been diagnosed with SE, Dr. Dham noted.

He said that the study is limited by the investigators’ inability to audit the database to review patient charts and the lack of morbidity and mortality data for patients once they left the hospital. Furthermore, the investigators could not differentiate between convulsive, nonconvulsive, and refractory SE because the ICD-9 coding does not allow it.

Dr. Dham said that he had no relevant financial disclosures.

NEW ORLEANS – How long does it take before the cumulative effect of repeated blows to the head result in significant cognitive changes? Preliminary results from a longitudinal study of boxers and mixed martial arts fighters suggest that it takes maybe a dozen years – but that anatomical changes begin showing up in half that time.

The results so far in 109 fighters suggest that "if you wait for people to get symptomatic, the disease has possibly progressed a fair amount," said Dr. Charles Bernick, lead investigator of the study and associate medical director of the Cleveland Clinic’s Lou Ruvo Center for Brain Health in Las Vegas.

Photo credit: Piotr Sikora/iStockphoto.com

Clinicians may need to be assessing fighters sooner for potential damage, he said at the annual meeting of the American Academy of Neurology. Although it is not yet known, perhaps rest periods or even stopping fighting altogether might halt the neurodegenerative process.

Dr. Bernick and his colleagues at the center aim to enroll 600 people in the Professional Fighters Brain Health Study by the time funding runs out 4 years from now. Because it is longitudinal, it has a running enrollment. Those already enrolled will be continually followed.

"The real payoff will be following these guys over time and looking at the trajectories," Dr. Bernick said in an interview. The investigators are conducting volumetric brain MRI and computerized cognitive testing. Participants also are tested for mood disorders and impulsivity, and they also undergo speech analysis as well, said Dr. Bernick.

The researchers obtain fighting history, including years of fighting and fights per year, from self-reports and published records. The study will also examine biomarkers, genetic profiles, and serum proteins that might be markers of damage, he said.

In the preliminary analysis, the investigators divided the fighters into three groups based on median years of fighting: less than 6 years, 6-12 years, and greater than 12 years. The relationship between exposure variables, brain volumetrics, and cognitive results were examined by correlational analysis.

The 32 fighters who fought 6 years or more had lower hippocampal and thalamic volumes. But cognitive changes – measured in lower scores on memory tests and processing speed – were found only in the 39 fighters who had fought more than 12 years. The relationships remained even after adjusting for the effect of age.

The ongoing study is funded by the Lincy Foundation. Dr. Bernick reported having no financial disclosures.

NEW ORLEANS – How long does it take before the cumulative effect of repeated blows to the head result in significant cognitive changes? Preliminary results from a longitudinal study of boxers and mixed martial arts fighters suggest that it takes maybe a dozen years – but that anatomical changes begin showing up in half that time.

The results so far in 109 fighters suggest that "if you wait for people to get symptomatic, the disease has possibly progressed a fair amount," said Dr. Charles Bernick, lead investigator of the study and associate medical director of the Cleveland Clinic’s Lou Ruvo Center for Brain Health in Las Vegas.

Photo credit: Piotr Sikora/iStockphoto.com

Clinicians may need to be assessing fighters sooner for potential damage, he said at the annual meeting of the American Academy of Neurology. Although it is not yet known, perhaps rest periods or even stopping fighting altogether might halt the neurodegenerative process.

Dr. Bernick and his colleagues at the center aim to enroll 600 people in the Professional Fighters Brain Health Study by the time funding runs out 4 years from now. Because it is longitudinal, it has a running enrollment. Those already enrolled will be continually followed.

"The real payoff will be following these guys over time and looking at the trajectories," Dr. Bernick said in an interview. The investigators are conducting volumetric brain MRI and computerized cognitive testing. Participants also are tested for mood disorders and impulsivity, and they also undergo speech analysis as well, said Dr. Bernick.

The researchers obtain fighting history, including years of fighting and fights per year, from self-reports and published records. The study will also examine biomarkers, genetic profiles, and serum proteins that might be markers of damage, he said.

In the preliminary analysis, the investigators divided the fighters into three groups based on median years of fighting: less than 6 years, 6-12 years, and greater than 12 years. The relationship between exposure variables, brain volumetrics, and cognitive results were examined by correlational analysis.

The 32 fighters who fought 6 years or more had lower hippocampal and thalamic volumes. But cognitive changes – measured in lower scores on memory tests and processing speed – were found only in the 39 fighters who had fought more than 12 years. The relationships remained even after adjusting for the effect of age.

The ongoing study is funded by the Lincy Foundation. Dr. Bernick reported having no financial disclosures.

NEW ORLEANS – How long does it take before the cumulative effect of repeated blows to the head result in significant cognitive changes? Preliminary results from a longitudinal study of boxers and mixed martial arts fighters suggest that it takes maybe a dozen years – but that anatomical changes begin showing up in half that time.

The results so far in 109 fighters suggest that "if you wait for people to get symptomatic, the disease has possibly progressed a fair amount," said Dr. Charles Bernick, lead investigator of the study and associate medical director of the Cleveland Clinic’s Lou Ruvo Center for Brain Health in Las Vegas.

Photo credit: Piotr Sikora/iStockphoto.com

Clinicians may need to be assessing fighters sooner for potential damage, he said at the annual meeting of the American Academy of Neurology. Although it is not yet known, perhaps rest periods or even stopping fighting altogether might halt the neurodegenerative process.

Dr. Bernick and his colleagues at the center aim to enroll 600 people in the Professional Fighters Brain Health Study by the time funding runs out 4 years from now. Because it is longitudinal, it has a running enrollment. Those already enrolled will be continually followed.

"The real payoff will be following these guys over time and looking at the trajectories," Dr. Bernick said in an interview. The investigators are conducting volumetric brain MRI and computerized cognitive testing. Participants also are tested for mood disorders and impulsivity, and they also undergo speech analysis as well, said Dr. Bernick.

The researchers obtain fighting history, including years of fighting and fights per year, from self-reports and published records. The study will also examine biomarkers, genetic profiles, and serum proteins that might be markers of damage, he said.

In the preliminary analysis, the investigators divided the fighters into three groups based on median years of fighting: less than 6 years, 6-12 years, and greater than 12 years. The relationship between exposure variables, brain volumetrics, and cognitive results were examined by correlational analysis.

The 32 fighters who fought 6 years or more had lower hippocampal and thalamic volumes. But cognitive changes – measured in lower scores on memory tests and processing speed – were found only in the 39 fighters who had fought more than 12 years. The relationships remained even after adjusting for the effect of age.

The ongoing study is funded by the Lincy Foundation. Dr. Bernick reported having no financial disclosures.

NEW ORLEANS – Women with epilepsy appear to have a significantly greater number of unintended pregnancies than does the general population and cite a wide variety of reasons for discontinuing different contraceptive methods, according to preliminary results from the Epilepsy Birth Control Registry.

In the survey of 350 women with epilepsy, pregnancy was unintended in 125 (86%) of the 146 women who had pregnancies and in 215 (63%) of the 340 total pregnancies. This was significantly higher than the rate of 49% observed in a general U.S. population survey of 7,643 women.

Jeff Evans/IMNG Medical Media

This was surprising to senior study investigator Dr. Andrew G. Herzog, director of the Harvard Neuroendocrine Unit at Beth Israel Deaconess Medical Center, Wellesley, Mass. "The epilepsy population, which is thought to have a lower fertility rate [than the general population], nevertheless had the higher unintended pregnancy rate," he said in an interview.

The frequency of unintended pregnancy differed significantly between various combinations of contraceptive methods and types of antiepileptic drug (AED), and was highest for those who used enzyme-inducing AEDs (EIAEDs) and hormonal birth control such as depot medroxyprogesterone acetate. EIAEDs also proved to be the only significant AED-related reason for stopping contraception, at least for women who were using hormonal birth control.

"There are some reciprocal interactions between antiepileptic drugs and contraceptive hormones, which can compromise both contraceptive efficacy and also seizure control," Dr. Herzog noted. "We now know that enzyme-inducing and glucuronidated AEDs such as lamotrigine interact with hormonal contraceptives." For instance, high estrogen levels decrease levels of lamotrigine but increase levels of EIAEDs.

Studies have shown that many women with epilepsy who take hormonal contraceptives also do not know that they can interact with AEDs or that some AEDs have a high teratogenic potential.

"Our goal is to get enough information so that we can develop some meaningful guidelines for safe and effective contraception for women with epilepsy ... and also for their health care providers," Dr. Herzog said. "Neurologists need to be informed and knowledgeable about the interactions between hormones and the antiepileptic drugs, and need to be comfortable in talking to their patients about contraception and these interactions because gynecologists are comfortable in discussing contraception, but they have a limited number of patients with epilepsy, like 1% perhaps."

The investigators promoted the Epilepsy Birth Control Registry through online advertisements and Facebook as an educational website for epilepsy birth control in which women could get educational material after taking a 30-question survey. It is the first community-based study of contraceptive methods and AED use in women with epilepsy.

Demographic characteristics of the survey respondents, aged 18-47 years, indicated that they were "somewhat younger than the general epilepsy population and somewhat better educated," Dr. Herzog said at the annual meeting of the American Academy of Neurology.

Respondents reported contraceptive methods including withdrawal, barrier, hormonal, hormonal-depot, and intrauterine device (IUD). AEDs were grouped into enzyme-inducing, non–enzyme-inducing, glucuronidated (lamotrigine), enzyme-inhibiting (valproate), or none.

All of the expected frequencies for contraceptive methods and AED categories assumed equal risk of stoppage and unintended pregnancies because no data are available to set expected values. In statistical comparisons, the contraceptive methods and AED categories were adjusted for differences in frequency of their use in the survey population.

Of 408 total stoppages of contraceptives, 214 (53%) were for adverse reasons – not because of a desire to become pregnant, sexual inactivity, or tubal ligation. Participants cited 22 different reasons for stopping their contraceptive method, which the investigators collated into 8 categories: menstrual disorder, increasing seizures, logistical issues related to the method, pregnancy on the method, concerns about the reliability of the method, headache, emotional changes, and concern about AED interaction.

Respondents stopped birth control for an adverse reason most often with depot medroxyprogesterone acetate (56%); followed by hormonal (oral pill, patch, or vaginal ring) (47%); withdrawal (38%); IUD (28%); and barrier (condom or diaphragm) (21%). Frequencies of stoppage for each of the categories of adverse reasons differed significantly between the contraceptive methods, Arielle Saporta, a research assistant in Dr. Herzog’s lab, reported at the meeting.

The reasons for stoppage varied from method to method. For withdrawal and barrier methods, they included reliability and pregnancy (as well as logistical concerns for barrier). Hormonal contraception was stopped over concerns about seizures and menstrual disorder (irregular cycles, heavy menses, or irregular bleeding). Depot medroxyprogesterone acetate was often stopped because of menstrual disorder and logistical reasons. IUDs were discontinued largely because of menstrual disorder.

Among the different types of AEDs, only EIAEDs were significantly associated with a reason for stopping birth control. For example, menstrual disorder as a reason for stopping birth control was significantly associated with use of EIAEDs. Overall, 29% of respondents who used EIAEDs and hormonal birth control cited menstrual disorder as a reason for stopping, which was twice as often as for women not taking AEDs.

An earlier report from the registry showed that 18% of women on hormonal contraceptives had worsening of their seizures, compared with 3% of women on nonhormonal contraceptives.

These results also led some audience members to wonder who was prescribing AEDs to women on unreliable contraceptive methods such as withdrawal. Indeed, only one-fourth of women who completed the survey consulted a neurologist about what contraceptive methods might be most appropriate for their type of epilepsy and treatment. This was a "surprise," Dr. Herzog said. "Either they don’t think their neurologist know about the topic, or maybe they are correct that [we] don’t know about the topic. And for gynecologists, epilepsy makes up only about 1% of their practice, so it’s not their major focus either."

The investigators now have 550 completed surveys and hope to get 1,000. They are planning to set up a prospective arm of the study in which patients can check back into the registry every 3 months, which will hopefully provide rates of unintended pregnancy for each kind of contraceptive in terms of woman-years of contraceptive use, which is the standard measurement for contraceptive efficacy.

The registry is funded in part by the Epilepsy Foundation. Dr. Herzog and Ms. Saporta had no relevant disclosures.

NEW ORLEANS – Women with epilepsy appear to have a significantly greater number of unintended pregnancies than does the general population and cite a wide variety of reasons for discontinuing different contraceptive methods, according to preliminary results from the Epilepsy Birth Control Registry.

In the survey of 350 women with epilepsy, pregnancy was unintended in 125 (86%) of the 146 women who had pregnancies and in 215 (63%) of the 340 total pregnancies. This was significantly higher than the rate of 49% observed in a general U.S. population survey of 7,643 women.

Jeff Evans/IMNG Medical Media

This was surprising to senior study investigator Dr. Andrew G. Herzog, director of the Harvard Neuroendocrine Unit at Beth Israel Deaconess Medical Center, Wellesley, Mass. "The epilepsy population, which is thought to have a lower fertility rate [than the general population], nevertheless had the higher unintended pregnancy rate," he said in an interview.

The frequency of unintended pregnancy differed significantly between various combinations of contraceptive methods and types of antiepileptic drug (AED), and was highest for those who used enzyme-inducing AEDs (EIAEDs) and hormonal birth control such as depot medroxyprogesterone acetate. EIAEDs also proved to be the only significant AED-related reason for stopping contraception, at least for women who were using hormonal birth control.

"There are some reciprocal interactions between antiepileptic drugs and contraceptive hormones, which can compromise both contraceptive efficacy and also seizure control," Dr. Herzog noted. "We now know that enzyme-inducing and glucuronidated AEDs such as lamotrigine interact with hormonal contraceptives." For instance, high estrogen levels decrease levels of lamotrigine but increase levels of EIAEDs.

Studies have shown that many women with epilepsy who take hormonal contraceptives also do not know that they can interact with AEDs or that some AEDs have a high teratogenic potential.

"Our goal is to get enough information so that we can develop some meaningful guidelines for safe and effective contraception for women with epilepsy ... and also for their health care providers," Dr. Herzog said. "Neurologists need to be informed and knowledgeable about the interactions between hormones and the antiepileptic drugs, and need to be comfortable in talking to their patients about contraception and these interactions because gynecologists are comfortable in discussing contraception, but they have a limited number of patients with epilepsy, like 1% perhaps."

The investigators promoted the Epilepsy Birth Control Registry through online advertisements and Facebook as an educational website for epilepsy birth control in which women could get educational material after taking a 30-question survey. It is the first community-based study of contraceptive methods and AED use in women with epilepsy.

Demographic characteristics of the survey respondents, aged 18-47 years, indicated that they were "somewhat younger than the general epilepsy population and somewhat better educated," Dr. Herzog said at the annual meeting of the American Academy of Neurology.

Respondents reported contraceptive methods including withdrawal, barrier, hormonal, hormonal-depot, and intrauterine device (IUD). AEDs were grouped into enzyme-inducing, non–enzyme-inducing, glucuronidated (lamotrigine), enzyme-inhibiting (valproate), or none.

All of the expected frequencies for contraceptive methods and AED categories assumed equal risk of stoppage and unintended pregnancies because no data are available to set expected values. In statistical comparisons, the contraceptive methods and AED categories were adjusted for differences in frequency of their use in the survey population.

Of 408 total stoppages of contraceptives, 214 (53%) were for adverse reasons – not because of a desire to become pregnant, sexual inactivity, or tubal ligation. Participants cited 22 different reasons for stopping their contraceptive method, which the investigators collated into 8 categories: menstrual disorder, increasing seizures, logistical issues related to the method, pregnancy on the method, concerns about the reliability of the method, headache, emotional changes, and concern about AED interaction.

Respondents stopped birth control for an adverse reason most often with depot medroxyprogesterone acetate (56%); followed by hormonal (oral pill, patch, or vaginal ring) (47%); withdrawal (38%); IUD (28%); and barrier (condom or diaphragm) (21%). Frequencies of stoppage for each of the categories of adverse reasons differed significantly between the contraceptive methods, Arielle Saporta, a research assistant in Dr. Herzog’s lab, reported at the meeting.

The reasons for stoppage varied from method to method. For withdrawal and barrier methods, they included reliability and pregnancy (as well as logistical concerns for barrier). Hormonal contraception was stopped over concerns about seizures and menstrual disorder (irregular cycles, heavy menses, or irregular bleeding). Depot medroxyprogesterone acetate was often stopped because of menstrual disorder and logistical reasons. IUDs were discontinued largely because of menstrual disorder.

Among the different types of AEDs, only EIAEDs were significantly associated with a reason for stopping birth control. For example, menstrual disorder as a reason for stopping birth control was significantly associated with use of EIAEDs. Overall, 29% of respondents who used EIAEDs and hormonal birth control cited menstrual disorder as a reason for stopping, which was twice as often as for women not taking AEDs.

An earlier report from the registry showed that 18% of women on hormonal contraceptives had worsening of their seizures, compared with 3% of women on nonhormonal contraceptives.

These results also led some audience members to wonder who was prescribing AEDs to women on unreliable contraceptive methods such as withdrawal. Indeed, only one-fourth of women who completed the survey consulted a neurologist about what contraceptive methods might be most appropriate for their type of epilepsy and treatment. This was a "surprise," Dr. Herzog said. "Either they don’t think their neurologist know about the topic, or maybe they are correct that [we] don’t know about the topic. And for gynecologists, epilepsy makes up only about 1% of their practice, so it’s not their major focus either."

The investigators now have 550 completed surveys and hope to get 1,000. They are planning to set up a prospective arm of the study in which patients can check back into the registry every 3 months, which will hopefully provide rates of unintended pregnancy for each kind of contraceptive in terms of woman-years of contraceptive use, which is the standard measurement for contraceptive efficacy.

The registry is funded in part by the Epilepsy Foundation. Dr. Herzog and Ms. Saporta had no relevant disclosures.

NEW ORLEANS – Women with epilepsy appear to have a significantly greater number of unintended pregnancies than does the general population and cite a wide variety of reasons for discontinuing different contraceptive methods, according to preliminary results from the Epilepsy Birth Control Registry.

In the survey of 350 women with epilepsy, pregnancy was unintended in 125 (86%) of the 146 women who had pregnancies and in 215 (63%) of the 340 total pregnancies. This was significantly higher than the rate of 49% observed in a general U.S. population survey of 7,643 women.

Jeff Evans/IMNG Medical Media

This was surprising to senior study investigator Dr. Andrew G. Herzog, director of the Harvard Neuroendocrine Unit at Beth Israel Deaconess Medical Center, Wellesley, Mass. "The epilepsy population, which is thought to have a lower fertility rate [than the general population], nevertheless had the higher unintended pregnancy rate," he said in an interview.

The frequency of unintended pregnancy differed significantly between various combinations of contraceptive methods and types of antiepileptic drug (AED), and was highest for those who used enzyme-inducing AEDs (EIAEDs) and hormonal birth control such as depot medroxyprogesterone acetate. EIAEDs also proved to be the only significant AED-related reason for stopping contraception, at least for women who were using hormonal birth control.

"There are some reciprocal interactions between antiepileptic drugs and contraceptive hormones, which can compromise both contraceptive efficacy and also seizure control," Dr. Herzog noted. "We now know that enzyme-inducing and glucuronidated AEDs such as lamotrigine interact with hormonal contraceptives." For instance, high estrogen levels decrease levels of lamotrigine but increase levels of EIAEDs.

Studies have shown that many women with epilepsy who take hormonal contraceptives also do not know that they can interact with AEDs or that some AEDs have a high teratogenic potential.

"Our goal is to get enough information so that we can develop some meaningful guidelines for safe and effective contraception for women with epilepsy ... and also for their health care providers," Dr. Herzog said. "Neurologists need to be informed and knowledgeable about the interactions between hormones and the antiepileptic drugs, and need to be comfortable in talking to their patients about contraception and these interactions because gynecologists are comfortable in discussing contraception, but they have a limited number of patients with epilepsy, like 1% perhaps."

The investigators promoted the Epilepsy Birth Control Registry through online advertisements and Facebook as an educational website for epilepsy birth control in which women could get educational material after taking a 30-question survey. It is the first community-based study of contraceptive methods and AED use in women with epilepsy.

Demographic characteristics of the survey respondents, aged 18-47 years, indicated that they were "somewhat younger than the general epilepsy population and somewhat better educated," Dr. Herzog said at the annual meeting of the American Academy of Neurology.

Respondents reported contraceptive methods including withdrawal, barrier, hormonal, hormonal-depot, and intrauterine device (IUD). AEDs were grouped into enzyme-inducing, non–enzyme-inducing, glucuronidated (lamotrigine), enzyme-inhibiting (valproate), or none.

All of the expected frequencies for contraceptive methods and AED categories assumed equal risk of stoppage and unintended pregnancies because no data are available to set expected values. In statistical comparisons, the contraceptive methods and AED categories were adjusted for differences in frequency of their use in the survey population.

Of 408 total stoppages of contraceptives, 214 (53%) were for adverse reasons – not because of a desire to become pregnant, sexual inactivity, or tubal ligation. Participants cited 22 different reasons for stopping their contraceptive method, which the investigators collated into 8 categories: menstrual disorder, increasing seizures, logistical issues related to the method, pregnancy on the method, concerns about the reliability of the method, headache, emotional changes, and concern about AED interaction.

Respondents stopped birth control for an adverse reason most often with depot medroxyprogesterone acetate (56%); followed by hormonal (oral pill, patch, or vaginal ring) (47%); withdrawal (38%); IUD (28%); and barrier (condom or diaphragm) (21%). Frequencies of stoppage for each of the categories of adverse reasons differed significantly between the contraceptive methods, Arielle Saporta, a research assistant in Dr. Herzog’s lab, reported at the meeting.

The reasons for stoppage varied from method to method. For withdrawal and barrier methods, they included reliability and pregnancy (as well as logistical concerns for barrier). Hormonal contraception was stopped over concerns about seizures and menstrual disorder (irregular cycles, heavy menses, or irregular bleeding). Depot medroxyprogesterone acetate was often stopped because of menstrual disorder and logistical reasons. IUDs were discontinued largely because of menstrual disorder.

Among the different types of AEDs, only EIAEDs were significantly associated with a reason for stopping birth control. For example, menstrual disorder as a reason for stopping birth control was significantly associated with use of EIAEDs. Overall, 29% of respondents who used EIAEDs and hormonal birth control cited menstrual disorder as a reason for stopping, which was twice as often as for women not taking AEDs.

An earlier report from the registry showed that 18% of women on hormonal contraceptives had worsening of their seizures, compared with 3% of women on nonhormonal contraceptives.

These results also led some audience members to wonder who was prescribing AEDs to women on unreliable contraceptive methods such as withdrawal. Indeed, only one-fourth of women who completed the survey consulted a neurologist about what contraceptive methods might be most appropriate for their type of epilepsy and treatment. This was a "surprise," Dr. Herzog said. "Either they don’t think their neurologist know about the topic, or maybe they are correct that [we] don’t know about the topic. And for gynecologists, epilepsy makes up only about 1% of their practice, so it’s not their major focus either."

The investigators now have 550 completed surveys and hope to get 1,000. They are planning to set up a prospective arm of the study in which patients can check back into the registry every 3 months, which will hopefully provide rates of unintended pregnancy for each kind of contraceptive in terms of woman-years of contraceptive use, which is the standard measurement for contraceptive efficacy.

The registry is funded in part by the Epilepsy Foundation. Dr. Herzog and Ms. Saporta had no relevant disclosures.

NEW ORLEANS – Like many other specialties – particularly cognitive specialties – neurology is under pressure to figure out how best to survive in an environment in which expenses are rising, but income is declining. So what are some strategies for staying in practice, choosing what type of practice is best, ensuring a steady income stream, and staying sane?

At the recent annual meeting of the American Academy of Neurology, several neurologists offered their personal take on preserving the pleasures of practice while maintaining revenues.

Dr. Laurence J. Kinsella, codirector of neurology for SSM Neurosciences Institute, St. Louis, noted that although median income for neurologists had risen fairly steadily since the mid-1990s, a neurologist’s value was very much dependent on what area of the country he or she practices in, whether it is urban or rural, and whether the practice is academic or private, or interventionist or cognitive.*

Choosing where to practice and the best type of practice is dependent on which options offer the best proximity to family or accommodation of a spouse’s needs, as well as the most professional growth, leadership potential, and collegiality, among other factors, said Dr. Kinsella, who is also vice chair of the AAN’s government affairs committee.

In the assessment of a group practice, for instance, be aware that survey data and published research have shown that the average turnover is 7% per year, and 60% of those who leave do so in the first 5 years. The biggest reasons for leaving include practice issues; compensation and location issues; and spousal concerns. Some questions to raise are whether the senior partners are advocates for equity for all partners, and whether the path to partnership is clearly stated, Dr. Kinsella said.

Before signing a contract with any group, it’s worthwhile to consult with an attorney who specializes in health care, he said. Keep in mind that everything is negotiable. Some key components to explore include salary and bonus; productivity scale; call schedule; pension and profit sharing; termination; and malpractice, health, and disability insurance.

"The most important thing is, you have to pay attention and be limber and adjust your models as things change."

Whether you take the academic, private, solo, or group path, the reimbursement challenges will be the same. The elimination of the Medicare consult codes in 2010 have led to a 6%-20% reduction in reimbursement, according to AAN survey data, Dr. Kinsella said.

There is a tool to assess the impact on a practice at www.mitsi.org/. One way to make up for lost revenue is to take a closer look at evaluation and management (E&M) codes, he added. At least 60% of neurologists’ billing is for E&M services. AAN provides templates for determining efficient and appropriate use of E&M codes. Dr. Kinsella said he advocated for the use of prolonged service codes such as 99354 (31-74 minutes) and 99355 (for each additional 30 minutes). "I’d encourage you to get comfortable with these. They are very good to use," he said.

Most neurologists also bill at level 4, then level 5 and level 3 for E&M, and they should be billing primarily level 5, Dr. Kinsella said. A level 5 consult requires more than just a single diagnosis.

Some 40% of neurology practice now comes from neurophysiology, such as sleep studies and electromyography/nerve conduction studies. These procedures pay better than E&M and thus are worth adding into a practice, he said.

Some other revenue-generating ideas include taking on a hospital directorship, such as stroke director; participating in clinical trials; giving botulinum toxin injections and nerve blocks for rotator cuff injuries, for instance; doing skin biopsies for small fiber neuropathy; and doing chart reviews for legal cases and interpretation of images.

Consider also moonlighting as a neurohospitalist. Dr. Kinsella’s practice offered 24/7 coverage to a hospital that suddenly lost a group of neurologists, which worked out well.

"The key is to leverage your scarcity," Dr. Kinsella said, noting that neurologists are in sparse supply and that many hospitals need coverage for call, stroke centers, and telemedicine.

Another avenue is to offer coverage for rural health clinics. Medicare has been assisting rural hospitals and clinics to recruit neurologists. With higher reimbursement in place to help these centers, working for a rural clinic can "cover your windshield cost" to make the drive and take the time away from practice, he said.

His suggestions for keeping practice fun? Get a clinical appointment to teach residents. Or have a different area of practice every day.

Dr. Elaine C. Jones, a colleague of Dr. Kinsella’s on the AAN government affairs committee, has taken a somewhat contrary path to getting satisfaction out of her practice by moving from an academic setting to set up her own solo practice.

She began practicing in the late 1990s at a large multispecialty group based at an academic hospital in Providence, R.I. By 2001, she was chief of neurology, but she felt as if the responsibility was not matched by an equal level of decision-making power. She decided that by going solo she could cut out the middleman on issues concerning staffing decisions, expenses, program development, and office renovations.

She consulted with other physicians in private practice, read up on various publications from the American Medical Association, and relied on her boyfriend, who had banking experience and a law degree, all of which helped her to decide which business model to use. She hired attorneys to help file the necessary paperwork to set up the practice. The hardest decision was naming the practice; she decided on Southern New England Neurology, with an eye on expanding in the future.

In 2005, Dr. Jones opened the practice in Bristol, R.I., renting space in a primary care practice building. Reaching this point had taken $40,000 in personal savings, $50,000 from a home-equity credit line, and a $30,000 equipment loan. Within 6 months, she had covered her costs, and within 18 months she had paid off the loan and was paying down the equity line.

An important initial investment was an electronic health record system, Dr. Jones said.

She began by working just 4 days a week, which gave her time for personal pursuits. But 3 years in, she had outgrown the space and the increased patient volume was taxing her existing staff. Dr. Jones was afraid to leave the bosom of the primary care group and its built-in referrals, but it had no additional room, so she decided to buy a property. She purchased a duplex and invested in extensive renovations, which took about a year to complete.

She has found private practice to be very rewarding because it gives her control over her scheduling, hours, and staffing, and no one is standing behind her pushing for an increase in productivity. But it requires a lot of focus on managing expenses.

In 2010 and 2011, Dr. Jones had a decline in reimbursement, but her patient volume was increasing. There are only so many patients she can see on her own, so she looked for ways to cut expenses and increase income. Accounting, for instance, had gone up to 20% of her expenses. She dismissed her bookkeeper and now does her own books. The health plan cost had increased by 8%, so when the policy came up for renewal, she found state incentives for small businesses, which allowed her to reduce that expense.

Initially, she had an experienced nurse practitioner on staff who helped maintain or increase patient volume. But her salary was more than she could bring in independently, so Dr. Jones decided to let her go.

She’s found ways to bring in new revenue – for instance, by offering botulinum toxin injections for chronic migraines and punch skin biopsies. Dr. Jones said that participating in Medicare’s incentive programs for meaningful use and electronic prescribing have also boosted revenue. "It’s a lot of work, and it changes how you do things, but it is a revenue stream," she said.

With demand outstripping supply, neurologists will continue to be in demand, but the Affordable Care Act and other pressures will still make it hard to practice, Dr. Jones said. She’s considering taking on some coverage with some local hospitals, but added that she’s "not thrilled with working harder" or on more nights and weekends, although she is not ruling out this option.

Nor is she ruling out selling her practice and getting out of medicine all together.

"The most important thing is, you have to pay attention and be limber and adjust your models as things change," said Dr. Jones. But, she acknowledged, "I don’t know if I’ll still be in neurology in 5 years."

Dr. Kinsella disclosed that he owns stock in Rural Healthcare Logistics and is a subcontractor for Premier Service Network. Dr. Jones had no disclosures.

*Correction, 7/13/2012: An earlier version of this story misstated Dr. Kinsella's professional position.

NEW ORLEANS – Like many other specialties – particularly cognitive specialties – neurology is under pressure to figure out how best to survive in an environment in which expenses are rising, but income is declining. So what are some strategies for staying in practice, choosing what type of practice is best, ensuring a steady income stream, and staying sane?

At the recent annual meeting of the American Academy of Neurology, several neurologists offered their personal take on preserving the pleasures of practice while maintaining revenues.

Dr. Laurence J. Kinsella, codirector of neurology for SSM Neurosciences Institute, St. Louis, noted that although median income for neurologists had risen fairly steadily since the mid-1990s, a neurologist’s value was very much dependent on what area of the country he or she practices in, whether it is urban or rural, and whether the practice is academic or private, or interventionist or cognitive.*

Choosing where to practice and the best type of practice is dependent on which options offer the best proximity to family or accommodation of a spouse’s needs, as well as the most professional growth, leadership potential, and collegiality, among other factors, said Dr. Kinsella, who is also vice chair of the AAN’s government affairs committee.

In the assessment of a group practice, for instance, be aware that survey data and published research have shown that the average turnover is 7% per year, and 60% of those who leave do so in the first 5 years. The biggest reasons for leaving include practice issues; compensation and location issues; and spousal concerns. Some questions to raise are whether the senior partners are advocates for equity for all partners, and whether the path to partnership is clearly stated, Dr. Kinsella said.

Before signing a contract with any group, it’s worthwhile to consult with an attorney who specializes in health care, he said. Keep in mind that everything is negotiable. Some key components to explore include salary and bonus; productivity scale; call schedule; pension and profit sharing; termination; and malpractice, health, and disability insurance.

"The most important thing is, you have to pay attention and be limber and adjust your models as things change."

Whether you take the academic, private, solo, or group path, the reimbursement challenges will be the same. The elimination of the Medicare consult codes in 2010 have led to a 6%-20% reduction in reimbursement, according to AAN survey data, Dr. Kinsella said.

There is a tool to assess the impact on a practice at www.mitsi.org/. One way to make up for lost revenue is to take a closer look at evaluation and management (E&M) codes, he added. At least 60% of neurologists’ billing is for E&M services. AAN provides templates for determining efficient and appropriate use of E&M codes. Dr. Kinsella said he advocated for the use of prolonged service codes such as 99354 (31-74 minutes) and 99355 (for each additional 30 minutes). "I’d encourage you to get comfortable with these. They are very good to use," he said.

Most neurologists also bill at level 4, then level 5 and level 3 for E&M, and they should be billing primarily level 5, Dr. Kinsella said. A level 5 consult requires more than just a single diagnosis.

Some 40% of neurology practice now comes from neurophysiology, such as sleep studies and electromyography/nerve conduction studies. These procedures pay better than E&M and thus are worth adding into a practice, he said.

Some other revenue-generating ideas include taking on a hospital directorship, such as stroke director; participating in clinical trials; giving botulinum toxin injections and nerve blocks for rotator cuff injuries, for instance; doing skin biopsies for small fiber neuropathy; and doing chart reviews for legal cases and interpretation of images.

Consider also moonlighting as a neurohospitalist. Dr. Kinsella’s practice offered 24/7 coverage to a hospital that suddenly lost a group of neurologists, which worked out well.

"The key is to leverage your scarcity," Dr. Kinsella said, noting that neurologists are in sparse supply and that many hospitals need coverage for call, stroke centers, and telemedicine.

Another avenue is to offer coverage for rural health clinics. Medicare has been assisting rural hospitals and clinics to recruit neurologists. With higher reimbursement in place to help these centers, working for a rural clinic can "cover your windshield cost" to make the drive and take the time away from practice, he said.

His suggestions for keeping practice fun? Get a clinical appointment to teach residents. Or have a different area of practice every day.

Dr. Elaine C. Jones, a colleague of Dr. Kinsella’s on the AAN government affairs committee, has taken a somewhat contrary path to getting satisfaction out of her practice by moving from an academic setting to set up her own solo practice.

She began practicing in the late 1990s at a large multispecialty group based at an academic hospital in Providence, R.I. By 2001, she was chief of neurology, but she felt as if the responsibility was not matched by an equal level of decision-making power. She decided that by going solo she could cut out the middleman on issues concerning staffing decisions, expenses, program development, and office renovations.

She consulted with other physicians in private practice, read up on various publications from the American Medical Association, and relied on her boyfriend, who had banking experience and a law degree, all of which helped her to decide which business model to use. She hired attorneys to help file the necessary paperwork to set up the practice. The hardest decision was naming the practice; she decided on Southern New England Neurology, with an eye on expanding in the future.

In 2005, Dr. Jones opened the practice in Bristol, R.I., renting space in a primary care practice building. Reaching this point had taken $40,000 in personal savings, $50,000 from a home-equity credit line, and a $30,000 equipment loan. Within 6 months, she had covered her costs, and within 18 months she had paid off the loan and was paying down the equity line.

An important initial investment was an electronic health record system, Dr. Jones said.

She began by working just 4 days a week, which gave her time for personal pursuits. But 3 years in, she had outgrown the space and the increased patient volume was taxing her existing staff. Dr. Jones was afraid to leave the bosom of the primary care group and its built-in referrals, but it had no additional room, so she decided to buy a property. She purchased a duplex and invested in extensive renovations, which took about a year to complete.

She has found private practice to be very rewarding because it gives her control over her scheduling, hours, and staffing, and no one is standing behind her pushing for an increase in productivity. But it requires a lot of focus on managing expenses.

In 2010 and 2011, Dr. Jones had a decline in reimbursement, but her patient volume was increasing. There are only so many patients she can see on her own, so she looked for ways to cut expenses and increase income. Accounting, for instance, had gone up to 20% of her expenses. She dismissed her bookkeeper and now does her own books. The health plan cost had increased by 8%, so when the policy came up for renewal, she found state incentives for small businesses, which allowed her to reduce that expense.

Initially, she had an experienced nurse practitioner on staff who helped maintain or increase patient volume. But her salary was more than she could bring in independently, so Dr. Jones decided to let her go.

She’s found ways to bring in new revenue – for instance, by offering botulinum toxin injections for chronic migraines and punch skin biopsies. Dr. Jones said that participating in Medicare’s incentive programs for meaningful use and electronic prescribing have also boosted revenue. "It’s a lot of work, and it changes how you do things, but it is a revenue stream," she said.

With demand outstripping supply, neurologists will continue to be in demand, but the Affordable Care Act and other pressures will still make it hard to practice, Dr. Jones said. She’s considering taking on some coverage with some local hospitals, but added that she’s "not thrilled with working harder" or on more nights and weekends, although she is not ruling out this option.

Nor is she ruling out selling her practice and getting out of medicine all together.

"The most important thing is, you have to pay attention and be limber and adjust your models as things change," said Dr. Jones. But, she acknowledged, "I don’t know if I’ll still be in neurology in 5 years."

Dr. Kinsella disclosed that he owns stock in Rural Healthcare Logistics and is a subcontractor for Premier Service Network. Dr. Jones had no disclosures.

*Correction, 7/13/2012: An earlier version of this story misstated Dr. Kinsella's professional position.

NEW ORLEANS – Like many other specialties – particularly cognitive specialties – neurology is under pressure to figure out how best to survive in an environment in which expenses are rising, but income is declining. So what are some strategies for staying in practice, choosing what type of practice is best, ensuring a steady income stream, and staying sane?

At the recent annual meeting of the American Academy of Neurology, several neurologists offered their personal take on preserving the pleasures of practice while maintaining revenues.

Dr. Laurence J. Kinsella, codirector of neurology for SSM Neurosciences Institute, St. Louis, noted that although median income for neurologists had risen fairly steadily since the mid-1990s, a neurologist’s value was very much dependent on what area of the country he or she practices in, whether it is urban or rural, and whether the practice is academic or private, or interventionist or cognitive.*

Choosing where to practice and the best type of practice is dependent on which options offer the best proximity to family or accommodation of a spouse’s needs, as well as the most professional growth, leadership potential, and collegiality, among other factors, said Dr. Kinsella, who is also vice chair of the AAN’s government affairs committee.

In the assessment of a group practice, for instance, be aware that survey data and published research have shown that the average turnover is 7% per year, and 60% of those who leave do so in the first 5 years. The biggest reasons for leaving include practice issues; compensation and location issues; and spousal concerns. Some questions to raise are whether the senior partners are advocates for equity for all partners, and whether the path to partnership is clearly stated, Dr. Kinsella said.

Before signing a contract with any group, it’s worthwhile to consult with an attorney who specializes in health care, he said. Keep in mind that everything is negotiable. Some key components to explore include salary and bonus; productivity scale; call schedule; pension and profit sharing; termination; and malpractice, health, and disability insurance.

"The most important thing is, you have to pay attention and be limber and adjust your models as things change."

Whether you take the academic, private, solo, or group path, the reimbursement challenges will be the same. The elimination of the Medicare consult codes in 2010 have led to a 6%-20% reduction in reimbursement, according to AAN survey data, Dr. Kinsella said.

There is a tool to assess the impact on a practice at www.mitsi.org/. One way to make up for lost revenue is to take a closer look at evaluation and management (E&M) codes, he added. At least 60% of neurologists’ billing is for E&M services. AAN provides templates for determining efficient and appropriate use of E&M codes. Dr. Kinsella said he advocated for the use of prolonged service codes such as 99354 (31-74 minutes) and 99355 (for each additional 30 minutes). "I’d encourage you to get comfortable with these. They are very good to use," he said.

Most neurologists also bill at level 4, then level 5 and level 3 for E&M, and they should be billing primarily level 5, Dr. Kinsella said. A level 5 consult requires more than just a single diagnosis.

Some 40% of neurology practice now comes from neurophysiology, such as sleep studies and electromyography/nerve conduction studies. These procedures pay better than E&M and thus are worth adding into a practice, he said.

Some other revenue-generating ideas include taking on a hospital directorship, such as stroke director; participating in clinical trials; giving botulinum toxin injections and nerve blocks for rotator cuff injuries, for instance; doing skin biopsies for small fiber neuropathy; and doing chart reviews for legal cases and interpretation of images.

Consider also moonlighting as a neurohospitalist. Dr. Kinsella’s practice offered 24/7 coverage to a hospital that suddenly lost a group of neurologists, which worked out well.

"The key is to leverage your scarcity," Dr. Kinsella said, noting that neurologists are in sparse supply and that many hospitals need coverage for call, stroke centers, and telemedicine.

Another avenue is to offer coverage for rural health clinics. Medicare has been assisting rural hospitals and clinics to recruit neurologists. With higher reimbursement in place to help these centers, working for a rural clinic can "cover your windshield cost" to make the drive and take the time away from practice, he said.

His suggestions for keeping practice fun? Get a clinical appointment to teach residents. Or have a different area of practice every day.

Dr. Elaine C. Jones, a colleague of Dr. Kinsella’s on the AAN government affairs committee, has taken a somewhat contrary path to getting satisfaction out of her practice by moving from an academic setting to set up her own solo practice.

She began practicing in the late 1990s at a large multispecialty group based at an academic hospital in Providence, R.I. By 2001, she was chief of neurology, but she felt as if the responsibility was not matched by an equal level of decision-making power. She decided that by going solo she could cut out the middleman on issues concerning staffing decisions, expenses, program development, and office renovations.

She consulted with other physicians in private practice, read up on various publications from the American Medical Association, and relied on her boyfriend, who had banking experience and a law degree, all of which helped her to decide which business model to use. She hired attorneys to help file the necessary paperwork to set up the practice. The hardest decision was naming the practice; she decided on Southern New England Neurology, with an eye on expanding in the future.

In 2005, Dr. Jones opened the practice in Bristol, R.I., renting space in a primary care practice building. Reaching this point had taken $40,000 in personal savings, $50,000 from a home-equity credit line, and a $30,000 equipment loan. Within 6 months, she had covered her costs, and within 18 months she had paid off the loan and was paying down the equity line.

An important initial investment was an electronic health record system, Dr. Jones said.

She began by working just 4 days a week, which gave her time for personal pursuits. But 3 years in, she had outgrown the space and the increased patient volume was taxing her existing staff. Dr. Jones was afraid to leave the bosom of the primary care group and its built-in referrals, but it had no additional room, so she decided to buy a property. She purchased a duplex and invested in extensive renovations, which took about a year to complete.

She has found private practice to be very rewarding because it gives her control over her scheduling, hours, and staffing, and no one is standing behind her pushing for an increase in productivity. But it requires a lot of focus on managing expenses.

In 2010 and 2011, Dr. Jones had a decline in reimbursement, but her patient volume was increasing. There are only so many patients she can see on her own, so she looked for ways to cut expenses and increase income. Accounting, for instance, had gone up to 20% of her expenses. She dismissed her bookkeeper and now does her own books. The health plan cost had increased by 8%, so when the policy came up for renewal, she found state incentives for small businesses, which allowed her to reduce that expense.

Initially, she had an experienced nurse practitioner on staff who helped maintain or increase patient volume. But her salary was more than she could bring in independently, so Dr. Jones decided to let her go.

She’s found ways to bring in new revenue – for instance, by offering botulinum toxin injections for chronic migraines and punch skin biopsies. Dr. Jones said that participating in Medicare’s incentive programs for meaningful use and electronic prescribing have also boosted revenue. "It’s a lot of work, and it changes how you do things, but it is a revenue stream," she said.

With demand outstripping supply, neurologists will continue to be in demand, but the Affordable Care Act and other pressures will still make it hard to practice, Dr. Jones said. She’s considering taking on some coverage with some local hospitals, but added that she’s "not thrilled with working harder" or on more nights and weekends, although she is not ruling out this option.

Nor is she ruling out selling her practice and getting out of medicine all together.

"The most important thing is, you have to pay attention and be limber and adjust your models as things change," said Dr. Jones. But, she acknowledged, "I don’t know if I’ll still be in neurology in 5 years."

Dr. Kinsella disclosed that he owns stock in Rural Healthcare Logistics and is a subcontractor for Premier Service Network. Dr. Jones had no disclosures.

*Correction, 7/13/2012: An earlier version of this story misstated Dr. Kinsella's professional position.