MADRID – Cerdulatinib, a single oral agent targeting two different pathways that lymphomas rely on for survival, produced rapid tumor responses in patients with relapsed or refractory non-Hodgkin lymphomas (NHL) in a phase II study.

The overall response rate among 47 patients enrolled in a phase II study was 50%, including responses among 67% of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 56% of patients with follicular lymphoma (FL), reported Paul A. Hamlin, MD, of the Memorial Sloan Kettering Cancer Center in New York.

MADRID – Cerdulatinib, a single oral agent targeting two different pathways that lymphomas rely on for survival, produced rapid tumor responses in patients with relapsed or refractory non-Hodgkin lymphomas (NHL) in a phase II study.

The overall response rate among 47 patients enrolled in a phase II study was 50%, including responses among 67% of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 56% of patients with follicular lymphoma (FL), reported Paul A. Hamlin, MD, of the Memorial Sloan Kettering Cancer Center in New York.

MADRID – Cerdulatinib, a single oral agent targeting two different pathways that lymphomas rely on for survival, produced rapid tumor responses in patients with relapsed or refractory non-Hodgkin lymphomas (NHL) in a phase II study.

The overall response rate among 47 patients enrolled in a phase II study was 50%, including responses among 67% of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 56% of patients with follicular lymphoma (FL), reported Paul A. Hamlin, MD, of the Memorial Sloan Kettering Cancer Center in New York.

CHICAGO – As the epidemic of opioid addiction and overdose deaths continues to surge, state and federal authorities are keeping a close eye on physicians who prescribe controlled substances.

Experts offer the following guidance on how well-meaning doctors can avoid coming under scrutiny for prescribing opioids and successfully manage investigations and audits.

1. Know who’s on the radar: The Drug Enforcement Agency (DEA) compiles a “black list” yearly of physicians and health care providers they plan to target for audits, said Natalia Mazina, a San Francisco–based attorney who specializes in health and pharmacy law. For 2017, the list includes physicians who have prior noncompliance records, providers who specialize in pain management, and those who dispense or administer large quantities of controlled substances.

2. Maintain proper records: Poor record keeping is a top reason that the DEA investigates health care providers for potential prescribing violations, said Dennis A. Wichern, a DEA agent with the Chicago Field Division. Federal law requires that registered practitioners who store or dispense controlled substances keep records of controlled substances coming in and out of the practice. That includes physicians who hand out samples of controlled substances to patients and also pertains to samples provided to doctors by pharmaceutical companies.

Alicia Gallegos/Frontline Medical News

3. Check the state database: Before prescribing opioids, check your state’s prescription drug monitoring program (PDMP) database, advises Ms. Mazina. At least 37 states have operational PDMPs that receive and distribute controlled substance prescription information to authorized users. About 11 states have enacted legislation to establish a PDMP, but some databases are not fully operational.

A state’s PDMP can reveal whether patients may be obtaining multiple controlled substance prescriptions from different doctors or doctor-shopping, Ms. Mazina said. Such due diligence helps inform treatment decisions and can assist a doctor’s case if a medical board or DEA investigation later arises.

“Even if your state law does not require you to check a patient’s history prior to prescribing, you have to check it to protect yourself,” she said. “If you want to avoid controlled substances problems, PDMP is the way to go.”

4. Establish an audit response plan: Have an audit response plan ready to roll should an inquiry arise, experts advise. The policies ensure that only approved information is released to authorities, and that all staff members are on the same page about how to react to audits, Ms. Mazina said.

Plans should clearly state what information can be collected and what data should be kept confidential. Financial information, for example, should be off limits, she said. Government agents are entitled to inventory, dispensary data, and records of receipts.

“Agents very often do the mirror image of the database, and they get too much information,” she said. “You don’t want to [allow] that.”

Train staff members how to respond to government authorities seeking audit information, and explain they have the right to refuse being interviewed, Ms. Mazina said.

“Train your employees on what’s going to happen if the DEA comes in,” she said. “If I don’t have clear policies and procedures, and I’m not trained, I might disclose everything and blame someone. That puts everyone in a [bad] position, because [authorities] will record everything and use it against [the practice].”

5. Confer with the experts: It doesn’t hurt to consult with other medical professionals, such as emergency physicians or pain management specialists, for practical advice on inventory policies or software suggestions. But when it comes to staying updated on new drug laws and regulations, confer with a health law attorney or compliance officer, Ms. Mazina said. The DEA website also includes useful information about recent laws and rules pertaining to prescription drugs, as does the Centers for Disease Control and Prevention website.

If an investigation or audit emerges, work with an attorney as early as possible. Often, practices wait until too late after an investigation begins to contact legal counsel, Ms. Mazina noted. The earlier an attorney gets involved, the sooner that person can build a strong case for the practice and work toward the best resolution.

“Very often, the physician thinks they are right, and there’s nothing for them to fear,” she said. “There is something for you to fear. There’s a lot at stake.”

[email protected]

On Twitter @legal_med

CHICAGO – As the epidemic of opioid addiction and overdose deaths continues to surge, state and federal authorities are keeping a close eye on physicians who prescribe controlled substances.

Experts offer the following guidance on how well-meaning doctors can avoid coming under scrutiny for prescribing opioids and successfully manage investigations and audits.

1. Know who’s on the radar: The Drug Enforcement Agency (DEA) compiles a “black list” yearly of physicians and health care providers they plan to target for audits, said Natalia Mazina, a San Francisco–based attorney who specializes in health and pharmacy law. For 2017, the list includes physicians who have prior noncompliance records, providers who specialize in pain management, and those who dispense or administer large quantities of controlled substances.

2. Maintain proper records: Poor record keeping is a top reason that the DEA investigates health care providers for potential prescribing violations, said Dennis A. Wichern, a DEA agent with the Chicago Field Division. Federal law requires that registered practitioners who store or dispense controlled substances keep records of controlled substances coming in and out of the practice. That includes physicians who hand out samples of controlled substances to patients and also pertains to samples provided to doctors by pharmaceutical companies.

Alicia Gallegos/Frontline Medical News

3. Check the state database: Before prescribing opioids, check your state’s prescription drug monitoring program (PDMP) database, advises Ms. Mazina. At least 37 states have operational PDMPs that receive and distribute controlled substance prescription information to authorized users. About 11 states have enacted legislation to establish a PDMP, but some databases are not fully operational.

A state’s PDMP can reveal whether patients may be obtaining multiple controlled substance prescriptions from different doctors or doctor-shopping, Ms. Mazina said. Such due diligence helps inform treatment decisions and can assist a doctor’s case if a medical board or DEA investigation later arises.

“Even if your state law does not require you to check a patient’s history prior to prescribing, you have to check it to protect yourself,” she said. “If you want to avoid controlled substances problems, PDMP is the way to go.”

4. Establish an audit response plan: Have an audit response plan ready to roll should an inquiry arise, experts advise. The policies ensure that only approved information is released to authorities, and that all staff members are on the same page about how to react to audits, Ms. Mazina said.

Plans should clearly state what information can be collected and what data should be kept confidential. Financial information, for example, should be off limits, she said. Government agents are entitled to inventory, dispensary data, and records of receipts.

“Agents very often do the mirror image of the database, and they get too much information,” she said. “You don’t want to [allow] that.”

Train staff members how to respond to government authorities seeking audit information, and explain they have the right to refuse being interviewed, Ms. Mazina said.

“Train your employees on what’s going to happen if the DEA comes in,” she said. “If I don’t have clear policies and procedures, and I’m not trained, I might disclose everything and blame someone. That puts everyone in a [bad] position, because [authorities] will record everything and use it against [the practice].”

5. Confer with the experts: It doesn’t hurt to consult with other medical professionals, such as emergency physicians or pain management specialists, for practical advice on inventory policies or software suggestions. But when it comes to staying updated on new drug laws and regulations, confer with a health law attorney or compliance officer, Ms. Mazina said. The DEA website also includes useful information about recent laws and rules pertaining to prescription drugs, as does the Centers for Disease Control and Prevention website.

If an investigation or audit emerges, work with an attorney as early as possible. Often, practices wait until too late after an investigation begins to contact legal counsel, Ms. Mazina noted. The earlier an attorney gets involved, the sooner that person can build a strong case for the practice and work toward the best resolution.

“Very often, the physician thinks they are right, and there’s nothing for them to fear,” she said. “There is something for you to fear. There’s a lot at stake.”

[email protected]

On Twitter @legal_med

CHICAGO – As the epidemic of opioid addiction and overdose deaths continues to surge, state and federal authorities are keeping a close eye on physicians who prescribe controlled substances.

Experts offer the following guidance on how well-meaning doctors can avoid coming under scrutiny for prescribing opioids and successfully manage investigations and audits.

1. Know who’s on the radar: The Drug Enforcement Agency (DEA) compiles a “black list” yearly of physicians and health care providers they plan to target for audits, said Natalia Mazina, a San Francisco–based attorney who specializes in health and pharmacy law. For 2017, the list includes physicians who have prior noncompliance records, providers who specialize in pain management, and those who dispense or administer large quantities of controlled substances.

2. Maintain proper records: Poor record keeping is a top reason that the DEA investigates health care providers for potential prescribing violations, said Dennis A. Wichern, a DEA agent with the Chicago Field Division. Federal law requires that registered practitioners who store or dispense controlled substances keep records of controlled substances coming in and out of the practice. That includes physicians who hand out samples of controlled substances to patients and also pertains to samples provided to doctors by pharmaceutical companies.

Alicia Gallegos/Frontline Medical News

3. Check the state database: Before prescribing opioids, check your state’s prescription drug monitoring program (PDMP) database, advises Ms. Mazina. At least 37 states have operational PDMPs that receive and distribute controlled substance prescription information to authorized users. About 11 states have enacted legislation to establish a PDMP, but some databases are not fully operational.

A state’s PDMP can reveal whether patients may be obtaining multiple controlled substance prescriptions from different doctors or doctor-shopping, Ms. Mazina said. Such due diligence helps inform treatment decisions and can assist a doctor’s case if a medical board or DEA investigation later arises.

“Even if your state law does not require you to check a patient’s history prior to prescribing, you have to check it to protect yourself,” she said. “If you want to avoid controlled substances problems, PDMP is the way to go.”

4. Establish an audit response plan: Have an audit response plan ready to roll should an inquiry arise, experts advise. The policies ensure that only approved information is released to authorities, and that all staff members are on the same page about how to react to audits, Ms. Mazina said.

Plans should clearly state what information can be collected and what data should be kept confidential. Financial information, for example, should be off limits, she said. Government agents are entitled to inventory, dispensary data, and records of receipts.

“Agents very often do the mirror image of the database, and they get too much information,” she said. “You don’t want to [allow] that.”

Train staff members how to respond to government authorities seeking audit information, and explain they have the right to refuse being interviewed, Ms. Mazina said.

“Train your employees on what’s going to happen if the DEA comes in,” she said. “If I don’t have clear policies and procedures, and I’m not trained, I might disclose everything and blame someone. That puts everyone in a [bad] position, because [authorities] will record everything and use it against [the practice].”

5. Confer with the experts: It doesn’t hurt to consult with other medical professionals, such as emergency physicians or pain management specialists, for practical advice on inventory policies or software suggestions. But when it comes to staying updated on new drug laws and regulations, confer with a health law attorney or compliance officer, Ms. Mazina said. The DEA website also includes useful information about recent laws and rules pertaining to prescription drugs, as does the Centers for Disease Control and Prevention website.

If an investigation or audit emerges, work with an attorney as early as possible. Often, practices wait until too late after an investigation begins to contact legal counsel, Ms. Mazina noted. The earlier an attorney gets involved, the sooner that person can build a strong case for the practice and work toward the best resolution.

“Very often, the physician thinks they are right, and there’s nothing for them to fear,” she said. “There is something for you to fear. There’s a lot at stake.”

[email protected]

On Twitter @legal_med

A friend sent me an article from the New Yorker called “The Algorithm Will See You Now,” in which Siddhartha Mukherjee, MD, author of the magisterial “The Emperor of All Maladies,” ponders the effect artificial intelligence may have on medicine. One possible outcome may be that computers replace radiologists and dermatologists. (They already beat top humans at Jeopardy, chess, and Go, so why not lick Homo sapiens at pattern recognition?)

No worries for me. When Watson takes over, I will be off somewhere playing shuffleboard.

• Thursday, August 6th, had sushi at a restaurant with friends.
• Sunday, September 3rd, watched science-fiction movie, unable to sleep that night.
• Monday, October 2nd, discarded fourth new detergent.

And so on.

In the meantime, several times each working day patients would troop in with randomly reoccurring conditions, atopic dermatitis above all, prompting dialogues like these:

“This is crazy! I never had anything like this before!”

“Well, actually, Ms. Jones, I treated you for the same thing in 2006.”

*********************

“This is bizarre! I never had this, and no one in my family ever did either.”

“I see. Well, here’s a prescription.”

“Come to think of it, my Mom had sensitive skin, and I get these dry patches on my arms and legs every winter.”

********************

“I’ve changed my soap three times and thrown out my makeup four times, and the rash keeps coming back. What should I do?”

“Stop throwing out your soap and makeup?”

And so on and on.

Sometimes, of course, semi-plausible causes seem to surface, such as stress. The question is, How useful is it to point this out? Consider the New Yorker case. Once the doctor “determined there is a link,” how might the conversation go?

“We have found the trigger, Mr. Smith. It’s stress.”

“Great! What should I do?”

“Don’t get laid off.”

No doctor (I hope) would ever say that, but patients present reports like the following all the time:

“As a kid, I was allergic to milk, but I’m not anymore.” (No, he wasn’t – he had infantile eczema that got blamed on milk.)

“Penicillin gave me hives.” (But, the hives lasted 6 weeks after the penicillin was stopped, which showed that the hives were idiopathic.)

“I’m very sensitive. I can’t use any moisturizer, any makeup, or all pills.” (People generate long litanies of sensitivities, piling one spurious correlation on another.)

Who benefits from “determining the link” when there isn’t any? Not the patients I’ve been seeing for forty years. Your patients? Maybe detergent manufacturers?

As to my errant pedagogy, with any luck, my students don’t remember a word I told them, a safe assumption for any teacher.

Either that or they don’t read the New Yorker.

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].

A friend sent me an article from the New Yorker called “The Algorithm Will See You Now,” in which Siddhartha Mukherjee, MD, author of the magisterial “The Emperor of All Maladies,” ponders the effect artificial intelligence may have on medicine. One possible outcome may be that computers replace radiologists and dermatologists. (They already beat top humans at Jeopardy, chess, and Go, so why not lick Homo sapiens at pattern recognition?)

No worries for me. When Watson takes over, I will be off somewhere playing shuffleboard.

• Thursday, August 6th, had sushi at a restaurant with friends.
• Sunday, September 3rd, watched science-fiction movie, unable to sleep that night.
• Monday, October 2nd, discarded fourth new detergent.

And so on.

In the meantime, several times each working day patients would troop in with randomly reoccurring conditions, atopic dermatitis above all, prompting dialogues like these:

“This is crazy! I never had anything like this before!”

“Well, actually, Ms. Jones, I treated you for the same thing in 2006.”

*********************

“This is bizarre! I never had this, and no one in my family ever did either.”

“I see. Well, here’s a prescription.”

“Come to think of it, my Mom had sensitive skin, and I get these dry patches on my arms and legs every winter.”

********************

“I’ve changed my soap three times and thrown out my makeup four times, and the rash keeps coming back. What should I do?”

“Stop throwing out your soap and makeup?”

And so on and on.

Sometimes, of course, semi-plausible causes seem to surface, such as stress. The question is, How useful is it to point this out? Consider the New Yorker case. Once the doctor “determined there is a link,” how might the conversation go?

“We have found the trigger, Mr. Smith. It’s stress.”

“Great! What should I do?”

“Don’t get laid off.”

No doctor (I hope) would ever say that, but patients present reports like the following all the time:

“As a kid, I was allergic to milk, but I’m not anymore.” (No, he wasn’t – he had infantile eczema that got blamed on milk.)

“Penicillin gave me hives.” (But, the hives lasted 6 weeks after the penicillin was stopped, which showed that the hives were idiopathic.)

“I’m very sensitive. I can’t use any moisturizer, any makeup, or all pills.” (People generate long litanies of sensitivities, piling one spurious correlation on another.)

Who benefits from “determining the link” when there isn’t any? Not the patients I’ve been seeing for forty years. Your patients? Maybe detergent manufacturers?

As to my errant pedagogy, with any luck, my students don’t remember a word I told them, a safe assumption for any teacher.

Either that or they don’t read the New Yorker.

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].

A friend sent me an article from the New Yorker called “The Algorithm Will See You Now,” in which Siddhartha Mukherjee, MD, author of the magisterial “The Emperor of All Maladies,” ponders the effect artificial intelligence may have on medicine. One possible outcome may be that computers replace radiologists and dermatologists. (They already beat top humans at Jeopardy, chess, and Go, so why not lick Homo sapiens at pattern recognition?)

No worries for me. When Watson takes over, I will be off somewhere playing shuffleboard.

• Thursday, August 6th, had sushi at a restaurant with friends.
• Sunday, September 3rd, watched science-fiction movie, unable to sleep that night.
• Monday, October 2nd, discarded fourth new detergent.

And so on.

In the meantime, several times each working day patients would troop in with randomly reoccurring conditions, atopic dermatitis above all, prompting dialogues like these:

“This is crazy! I never had anything like this before!”

“Well, actually, Ms. Jones, I treated you for the same thing in 2006.”

*********************

“This is bizarre! I never had this, and no one in my family ever did either.”

“I see. Well, here’s a prescription.”

“Come to think of it, my Mom had sensitive skin, and I get these dry patches on my arms and legs every winter.”

********************

“I’ve changed my soap three times and thrown out my makeup four times, and the rash keeps coming back. What should I do?”

“Stop throwing out your soap and makeup?”

And so on and on.

Sometimes, of course, semi-plausible causes seem to surface, such as stress. The question is, How useful is it to point this out? Consider the New Yorker case. Once the doctor “determined there is a link,” how might the conversation go?

“We have found the trigger, Mr. Smith. It’s stress.”

“Great! What should I do?”

“Don’t get laid off.”

No doctor (I hope) would ever say that, but patients present reports like the following all the time:

“As a kid, I was allergic to milk, but I’m not anymore.” (No, he wasn’t – he had infantile eczema that got blamed on milk.)

“Penicillin gave me hives.” (But, the hives lasted 6 weeks after the penicillin was stopped, which showed that the hives were idiopathic.)

“I’m very sensitive. I can’t use any moisturizer, any makeup, or all pills.” (People generate long litanies of sensitivities, piling one spurious correlation on another.)

Who benefits from “determining the link” when there isn’t any? Not the patients I’ve been seeing for forty years. Your patients? Maybe detergent manufacturers?

As to my errant pedagogy, with any luck, my students don’t remember a word I told them, a safe assumption for any teacher.

Either that or they don’t read the New Yorker.

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].

VANCOUVER—Inhaled levodopa significantly improves motor function during off periods in patients with Parkinson’s disease, according to phase III trial results presented at the 21st International Congress of Parkinson’s Disease and Movement Disorders.

Levodopa inhalation powder, CVT-301, is being developed by Acorda Therapeutics in Ardsley, New York, for intermittent treatment of off periods. The treatment improved motor scores in a phase II study.

Peter A. LeWitt, MD, Professor of Neurology at Henry Ford Hospital and Wayne State University School of Medicine in Detroit, and colleagues conducted the phase III SPAN-PD study, a 12-week, double-blind, multinational trial, to assess the treatment’s efficacy and safety. The investigators randomized 339 patients 1:1:1 to inhaled placebo, CVT-301 (84 mg), or CVT-301 (60 mg) for use up to five times daily as needed.

Patients had idiopathic Parkinson’s disease and two or more hours per day of off time, excluding morning off time. Patients were receiving a stable dopa decarboxylase inhibitor and levodopa regimen, and they did not have chronic respiratory disease within the previous five years. Patients’ mean age was 63.3, and 73.5% were male.

The primary end point was change in Unified Parkinson’s Disease Rating Scale (UPDRS) Part III motor score from predose to 30 minutes post dose with CVT-301 (84 mg) or placebo at week 12, when subjects were evaluated during an off period.

At 30 minutes, improvement in motor scores was significantly greater among patients who received CVT-301 (84 mg), compared with patients who received placebo (9.83 vs 5.91).

A greater proportion of patients who received CVT-301 were in an on state (ie, treatment benefited mobility, slowness, and stiffness) at 60 minutes, compared with patients who received placebo (57.7% of patients who received CVT-301 [84 mg], 55.6% of patients who received CVT-301 [60 mg], and 36.1% of patients who received placebo).

Motor improvement occurred as soon as 10 minutes after the 84-mg dose. Furthermore, a greater percentage of patients reported improvement in Patient Global Impression of Change with CVT-301 than with placebo.

Inhaled levodopa was generally well tolerated, and the adverse events and safety profile were consistent with those in a phase IIb study.

Cough was the most common adverse event with CVT-301 versus placebo (15% vs 1.8%). Other adverse events in the 84-mg group included upper respiratory tract infection (6.1%), nausea (5.3%), and sputum discoloration (5.3%).

—Jake Remaly

VANCOUVER—Inhaled levodopa significantly improves motor function during off periods in patients with Parkinson’s disease, according to phase III trial results presented at the 21st International Congress of Parkinson’s Disease and Movement Disorders.

Levodopa inhalation powder, CVT-301, is being developed by Acorda Therapeutics in Ardsley, New York, for intermittent treatment of off periods. The treatment improved motor scores in a phase II study.

Peter A. LeWitt, MD, Professor of Neurology at Henry Ford Hospital and Wayne State University School of Medicine in Detroit, and colleagues conducted the phase III SPAN-PD study, a 12-week, double-blind, multinational trial, to assess the treatment’s efficacy and safety. The investigators randomized 339 patients 1:1:1 to inhaled placebo, CVT-301 (84 mg), or CVT-301 (60 mg) for use up to five times daily as needed.

Patients had idiopathic Parkinson’s disease and two or more hours per day of off time, excluding morning off time. Patients were receiving a stable dopa decarboxylase inhibitor and levodopa regimen, and they did not have chronic respiratory disease within the previous five years. Patients’ mean age was 63.3, and 73.5% were male.

The primary end point was change in Unified Parkinson’s Disease Rating Scale (UPDRS) Part III motor score from predose to 30 minutes post dose with CVT-301 (84 mg) or placebo at week 12, when subjects were evaluated during an off period.

At 30 minutes, improvement in motor scores was significantly greater among patients who received CVT-301 (84 mg), compared with patients who received placebo (9.83 vs 5.91).

A greater proportion of patients who received CVT-301 were in an on state (ie, treatment benefited mobility, slowness, and stiffness) at 60 minutes, compared with patients who received placebo (57.7% of patients who received CVT-301 [84 mg], 55.6% of patients who received CVT-301 [60 mg], and 36.1% of patients who received placebo).

Motor improvement occurred as soon as 10 minutes after the 84-mg dose. Furthermore, a greater percentage of patients reported improvement in Patient Global Impression of Change with CVT-301 than with placebo.

Inhaled levodopa was generally well tolerated, and the adverse events and safety profile were consistent with those in a phase IIb study.

Cough was the most common adverse event with CVT-301 versus placebo (15% vs 1.8%). Other adverse events in the 84-mg group included upper respiratory tract infection (6.1%), nausea (5.3%), and sputum discoloration (5.3%).

—Jake Remaly

VANCOUVER—Inhaled levodopa significantly improves motor function during off periods in patients with Parkinson’s disease, according to phase III trial results presented at the 21st International Congress of Parkinson’s Disease and Movement Disorders.

Levodopa inhalation powder, CVT-301, is being developed by Acorda Therapeutics in Ardsley, New York, for intermittent treatment of off periods. The treatment improved motor scores in a phase II study.

Peter A. LeWitt, MD, Professor of Neurology at Henry Ford Hospital and Wayne State University School of Medicine in Detroit, and colleagues conducted the phase III SPAN-PD study, a 12-week, double-blind, multinational trial, to assess the treatment’s efficacy and safety. The investigators randomized 339 patients 1:1:1 to inhaled placebo, CVT-301 (84 mg), or CVT-301 (60 mg) for use up to five times daily as needed.

Patients had idiopathic Parkinson’s disease and two or more hours per day of off time, excluding morning off time. Patients were receiving a stable dopa decarboxylase inhibitor and levodopa regimen, and they did not have chronic respiratory disease within the previous five years. Patients’ mean age was 63.3, and 73.5% were male.

The primary end point was change in Unified Parkinson’s Disease Rating Scale (UPDRS) Part III motor score from predose to 30 minutes post dose with CVT-301 (84 mg) or placebo at week 12, when subjects were evaluated during an off period.

At 30 minutes, improvement in motor scores was significantly greater among patients who received CVT-301 (84 mg), compared with patients who received placebo (9.83 vs 5.91).

A greater proportion of patients who received CVT-301 were in an on state (ie, treatment benefited mobility, slowness, and stiffness) at 60 minutes, compared with patients who received placebo (57.7% of patients who received CVT-301 [84 mg], 55.6% of patients who received CVT-301 [60 mg], and 36.1% of patients who received placebo).

Motor improvement occurred as soon as 10 minutes after the 84-mg dose. Furthermore, a greater percentage of patients reported improvement in Patient Global Impression of Change with CVT-301 than with placebo.

Inhaled levodopa was generally well tolerated, and the adverse events and safety profile were consistent with those in a phase IIb study.

Cough was the most common adverse event with CVT-301 versus placebo (15% vs 1.8%). Other adverse events in the 84-mg group included upper respiratory tract infection (6.1%), nausea (5.3%), and sputum discoloration (5.3%).

—Jake Remaly

The Food and Drug Administration has approved dabrafenib in combination with trametinib for patients with BRAF V600E mutation-positive metastatic non–small cell lung cancer (NSCLC).

The FDA also approved a diagnostic, the Oncomine Dx Target Test, a next-generation sequencing test to detect gene mutations or alterations, including BRAF, from a single tissue specimen, the FDA reported in a statement.

[email protected]

The Food and Drug Administration has approved dabrafenib in combination with trametinib for patients with BRAF V600E mutation-positive metastatic non–small cell lung cancer (NSCLC).

The FDA also approved a diagnostic, the Oncomine Dx Target Test, a next-generation sequencing test to detect gene mutations or alterations, including BRAF, from a single tissue specimen, the FDA reported in a statement.

[email protected]

The Food and Drug Administration has approved dabrafenib in combination with trametinib for patients with BRAF V600E mutation-positive metastatic non–small cell lung cancer (NSCLC).

The FDA also approved a diagnostic, the Oncomine Dx Target Test, a next-generation sequencing test to detect gene mutations or alterations, including BRAF, from a single tissue specimen, the FDA reported in a statement.

[email protected]

MIAMI—Advances in genetic testing have enabled precise identification of many spinocerebellar ataxias, but no pharmacologic therapy for the disorders has been approved, according to an overview presented at the First Pan American Parkinson’s Disease and Movement Disorders Congress. Nevertheless, the literature does indicate that various therapies have beneficial effects, said Theresa Zesiewicz, MD, Director of the University of South Florida Ataxia Research Center in Tampa.

She and her colleagues examined the evidence from the past 40 years of research on ataxia. The recommendations that they developed about treatment options currently are in press.

The Evidence for Pharmaceutical Treatment

“One of the most robust treatments for spinocerebellar ataxias … is going to be 4-aminopyridine for episodic ataxia type II,” said Dr. Zesiewicz. The drug is approved as a treatment for multiple sclerosis, and researchers have examined it in a double-blind, placebo-controlled trial of patients with episodic ataxia type II. After three months of treatment, the median number of monthly attacks was about 1.5 in participants who received 15 mg/day of 4-aminopyridine, compared with 6.5 for controls. The drug is fairly well tolerated and also can be used to treat downbeat nystagmus.

Two recent studies have investigated the effects of riluzole, a treatment for amyotrophic lateral sclerosis, in patients with various ataxias. Ristori et al examined 40 patients with ataxia of mixed etiology (eg, fragile X-associated tremor/ataxia syndrome, Friedreich’s ataxia, spinocerebellar ataxia, and multiple system atrophy). Patients received 100 mg/day of riluzole or placebo for eight weeks. After four weeks of treatment, about 47% of the riluzole group had a five-point improvement on the International Cooperative Ataxia Rating Scale (ICARS), compared with 5% in the placebo group. After eight weeks, 68% of the riluzole group had this outcome, compared with 5% of the placebo group.

In a 12-month study, Romano et al randomized 60 patients with spinocerebellar ataxia or Friedreich’s ataxia to 50 mg of riluzole b.i.d. or placebo. At 12 months, the proportion of patients with a decrease in Scale for the Assessment and Rating of Ataxia (SARA) score was 50% in the riluzole group, compared with 11% in the placebo group. The mean change in SARA score was greater in the riluzole group (2.6), compared with controls (1.39). The clinical relevance of the improvements in these two studies, however, is uncertain, said Dr. Zesiewicz.

An ongoing phase III study is examining a prodrug of riluzole in 120 patients with spinocerebellar ataxia. Various doses are being examined, and the treatment period will be eight weeks.

In a 1983 study, 250 patients with spinocerebellar ataxia were randomized to thyrotropin-releasing hormone or placebo. Outcomes were reported using a visual analog scale. Participants receiving thyrotropin-releasing hormone had improvement in dysarthria, stance, and gait, but the clinical significance is questionable, said Dr. Zesiewicz.

She and her colleagues compared varenicline, a drug approved for smoking cessation, with placebo in patients with spinocerebellar ataxia type III. After a four-week titration period, patients received treatment for four weeks. The investigators observed significant improvements in gait, stance, and rapid alternating movements among patients receiving varenicline. After data correction, the improvement in rapid alternating movements remained significant. Varenicline has been associated with suicide risk, but Dr. Zesiewicz and colleagues noted a trend toward improvement in Beck Depression Scale among treated participants. Approximately 40% of patients receiving varenicline dropped out of the study, however, because of tremulousness, weakness, and unpleasant dreams.

Examining Nonpharmacologic Options

In addition to pharmacotherapy, some nonpharmacologic treatments may improve function in spinocerebellar ataxia. In one double-blind trial, researchers randomized participants with various ataxias to a single session of transcranial magnetic stimulation (TMS) or sham stimulation. TMS was associated with improvement in SARA score and cerebellar motor function at 21 days. “Harvard just finished a TMS study, and we are waiting for results from that,” said Dr. Zesiewicz.

“Physical therapy is vital for patients with spinocerebellar ataxia,” she continued. One study indicated that intensive exercises such as core strength training, stepping, and dynamic balance yielded significant increases in the Berg Balance Scale. In another randomized controlled trial, four weeks of physical and occupational therapy were associated with a three-point decrease in SARA score. In addition, patients with spinocerebellar ataxia had a two-point decrease in ICARS score after undergoing four weeks of intensive cycling.

A Search for Future Therapies

Investigations of new potential treatments for spinocerebellar ataxia are ongoing. Researchers published the results of a phase II study of IV trehalose in January. Participants’ SARA score remained stable after six months of treatment.

Mesenchymal stem cells may one day provide benefits for patients. After one month of treatment with mesenchymal stromal cells, study participants with spinocerebellar ataxia had improved walking, standing, slow movement, and fine movements. Patients returned to their pretreatment condition after a few months, however.

In addition, screens of small molecules may reveal possible new therapies. One such screen identified aripiprazole as a candidate, and the drug increased longevity in a Drosophila model of Machado-Joseph disease.

“We are looking for great things. We are looking for a cure. But we will use what we have now,” Dr. Zesiewicz concluded.

—Erik Greb

Suggested Reading

Lei LF, Yang GP, Wang JL, et al. Safety and efficacy of valproic acid treatment in SCA3/MJD patients. Parkinsonism Relat Disord. 2016;26:55-61.

Ristori G, Romano S, Visconti A, et al. Riluzole in cerebellar ataxia: a randomized, double-blind, placebo-controlled pilot trial. Neurology. 2010;74(10):839-845.

Romano S, Coarelli G, Marcotulli C, et al. Riluzole in patients with hereditary cerebellar ataxia: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2015;14(10):985-891.

Strupp M, Kalla R, Claassen J, et al. A randomized trial of 4-aminopyridine in EA2 and related familial episodic ataxias. Neurology. 2011;77(3):269-275.

Zesiewicz TA, Greenstein PE, Sullivan KL, et al. A randomized trial of varenicline (Chantix) for the treatment of spinocerebellar ataxia type 3. Neurology. 2012;78(8):545-550.

MIAMI—Advances in genetic testing have enabled precise identification of many spinocerebellar ataxias, but no pharmacologic therapy for the disorders has been approved, according to an overview presented at the First Pan American Parkinson’s Disease and Movement Disorders Congress. Nevertheless, the literature does indicate that various therapies have beneficial effects, said Theresa Zesiewicz, MD, Director of the University of South Florida Ataxia Research Center in Tampa.

She and her colleagues examined the evidence from the past 40 years of research on ataxia. The recommendations that they developed about treatment options currently are in press.

The Evidence for Pharmaceutical Treatment

“One of the most robust treatments for spinocerebellar ataxias … is going to be 4-aminopyridine for episodic ataxia type II,” said Dr. Zesiewicz. The drug is approved as a treatment for multiple sclerosis, and researchers have examined it in a double-blind, placebo-controlled trial of patients with episodic ataxia type II. After three months of treatment, the median number of monthly attacks was about 1.5 in participants who received 15 mg/day of 4-aminopyridine, compared with 6.5 for controls. The drug is fairly well tolerated and also can be used to treat downbeat nystagmus.

Two recent studies have investigated the effects of riluzole, a treatment for amyotrophic lateral sclerosis, in patients with various ataxias. Ristori et al examined 40 patients with ataxia of mixed etiology (eg, fragile X-associated tremor/ataxia syndrome, Friedreich’s ataxia, spinocerebellar ataxia, and multiple system atrophy). Patients received 100 mg/day of riluzole or placebo for eight weeks. After four weeks of treatment, about 47% of the riluzole group had a five-point improvement on the International Cooperative Ataxia Rating Scale (ICARS), compared with 5% in the placebo group. After eight weeks, 68% of the riluzole group had this outcome, compared with 5% of the placebo group.

In a 12-month study, Romano et al randomized 60 patients with spinocerebellar ataxia or Friedreich’s ataxia to 50 mg of riluzole b.i.d. or placebo. At 12 months, the proportion of patients with a decrease in Scale for the Assessment and Rating of Ataxia (SARA) score was 50% in the riluzole group, compared with 11% in the placebo group. The mean change in SARA score was greater in the riluzole group (2.6), compared with controls (1.39). The clinical relevance of the improvements in these two studies, however, is uncertain, said Dr. Zesiewicz.

An ongoing phase III study is examining a prodrug of riluzole in 120 patients with spinocerebellar ataxia. Various doses are being examined, and the treatment period will be eight weeks.

In a 1983 study, 250 patients with spinocerebellar ataxia were randomized to thyrotropin-releasing hormone or placebo. Outcomes were reported using a visual analog scale. Participants receiving thyrotropin-releasing hormone had improvement in dysarthria, stance, and gait, but the clinical significance is questionable, said Dr. Zesiewicz.

She and her colleagues compared varenicline, a drug approved for smoking cessation, with placebo in patients with spinocerebellar ataxia type III. After a four-week titration period, patients received treatment for four weeks. The investigators observed significant improvements in gait, stance, and rapid alternating movements among patients receiving varenicline. After data correction, the improvement in rapid alternating movements remained significant. Varenicline has been associated with suicide risk, but Dr. Zesiewicz and colleagues noted a trend toward improvement in Beck Depression Scale among treated participants. Approximately 40% of patients receiving varenicline dropped out of the study, however, because of tremulousness, weakness, and unpleasant dreams.

Examining Nonpharmacologic Options

In addition to pharmacotherapy, some nonpharmacologic treatments may improve function in spinocerebellar ataxia. In one double-blind trial, researchers randomized participants with various ataxias to a single session of transcranial magnetic stimulation (TMS) or sham stimulation. TMS was associated with improvement in SARA score and cerebellar motor function at 21 days. “Harvard just finished a TMS study, and we are waiting for results from that,” said Dr. Zesiewicz.

“Physical therapy is vital for patients with spinocerebellar ataxia,” she continued. One study indicated that intensive exercises such as core strength training, stepping, and dynamic balance yielded significant increases in the Berg Balance Scale. In another randomized controlled trial, four weeks of physical and occupational therapy were associated with a three-point decrease in SARA score. In addition, patients with spinocerebellar ataxia had a two-point decrease in ICARS score after undergoing four weeks of intensive cycling.

A Search for Future Therapies

Investigations of new potential treatments for spinocerebellar ataxia are ongoing. Researchers published the results of a phase II study of IV trehalose in January. Participants’ SARA score remained stable after six months of treatment.

Mesenchymal stem cells may one day provide benefits for patients. After one month of treatment with mesenchymal stromal cells, study participants with spinocerebellar ataxia had improved walking, standing, slow movement, and fine movements. Patients returned to their pretreatment condition after a few months, however.

In addition, screens of small molecules may reveal possible new therapies. One such screen identified aripiprazole as a candidate, and the drug increased longevity in a Drosophila model of Machado-Joseph disease.

“We are looking for great things. We are looking for a cure. But we will use what we have now,” Dr. Zesiewicz concluded.

—Erik Greb

Suggested Reading

Lei LF, Yang GP, Wang JL, et al. Safety and efficacy of valproic acid treatment in SCA3/MJD patients. Parkinsonism Relat Disord. 2016;26:55-61.

Ristori G, Romano S, Visconti A, et al. Riluzole in cerebellar ataxia: a randomized, double-blind, placebo-controlled pilot trial. Neurology. 2010;74(10):839-845.

Romano S, Coarelli G, Marcotulli C, et al. Riluzole in patients with hereditary cerebellar ataxia: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2015;14(10):985-891.

Strupp M, Kalla R, Claassen J, et al. A randomized trial of 4-aminopyridine in EA2 and related familial episodic ataxias. Neurology. 2011;77(3):269-275.

Zesiewicz TA, Greenstein PE, Sullivan KL, et al. A randomized trial of varenicline (Chantix) for the treatment of spinocerebellar ataxia type 3. Neurology. 2012;78(8):545-550.

MIAMI—Advances in genetic testing have enabled precise identification of many spinocerebellar ataxias, but no pharmacologic therapy for the disorders has been approved, according to an overview presented at the First Pan American Parkinson’s Disease and Movement Disorders Congress. Nevertheless, the literature does indicate that various therapies have beneficial effects, said Theresa Zesiewicz, MD, Director of the University of South Florida Ataxia Research Center in Tampa.

She and her colleagues examined the evidence from the past 40 years of research on ataxia. The recommendations that they developed about treatment options currently are in press.

The Evidence for Pharmaceutical Treatment

“One of the most robust treatments for spinocerebellar ataxias … is going to be 4-aminopyridine for episodic ataxia type II,” said Dr. Zesiewicz. The drug is approved as a treatment for multiple sclerosis, and researchers have examined it in a double-blind, placebo-controlled trial of patients with episodic ataxia type II. After three months of treatment, the median number of monthly attacks was about 1.5 in participants who received 15 mg/day of 4-aminopyridine, compared with 6.5 for controls. The drug is fairly well tolerated and also can be used to treat downbeat nystagmus.

Two recent studies have investigated the effects of riluzole, a treatment for amyotrophic lateral sclerosis, in patients with various ataxias. Ristori et al examined 40 patients with ataxia of mixed etiology (eg, fragile X-associated tremor/ataxia syndrome, Friedreich’s ataxia, spinocerebellar ataxia, and multiple system atrophy). Patients received 100 mg/day of riluzole or placebo for eight weeks. After four weeks of treatment, about 47% of the riluzole group had a five-point improvement on the International Cooperative Ataxia Rating Scale (ICARS), compared with 5% in the placebo group. After eight weeks, 68% of the riluzole group had this outcome, compared with 5% of the placebo group.

In a 12-month study, Romano et al randomized 60 patients with spinocerebellar ataxia or Friedreich’s ataxia to 50 mg of riluzole b.i.d. or placebo. At 12 months, the proportion of patients with a decrease in Scale for the Assessment and Rating of Ataxia (SARA) score was 50% in the riluzole group, compared with 11% in the placebo group. The mean change in SARA score was greater in the riluzole group (2.6), compared with controls (1.39). The clinical relevance of the improvements in these two studies, however, is uncertain, said Dr. Zesiewicz.

An ongoing phase III study is examining a prodrug of riluzole in 120 patients with spinocerebellar ataxia. Various doses are being examined, and the treatment period will be eight weeks.

In a 1983 study, 250 patients with spinocerebellar ataxia were randomized to thyrotropin-releasing hormone or placebo. Outcomes were reported using a visual analog scale. Participants receiving thyrotropin-releasing hormone had improvement in dysarthria, stance, and gait, but the clinical significance is questionable, said Dr. Zesiewicz.

She and her colleagues compared varenicline, a drug approved for smoking cessation, with placebo in patients with spinocerebellar ataxia type III. After a four-week titration period, patients received treatment for four weeks. The investigators observed significant improvements in gait, stance, and rapid alternating movements among patients receiving varenicline. After data correction, the improvement in rapid alternating movements remained significant. Varenicline has been associated with suicide risk, but Dr. Zesiewicz and colleagues noted a trend toward improvement in Beck Depression Scale among treated participants. Approximately 40% of patients receiving varenicline dropped out of the study, however, because of tremulousness, weakness, and unpleasant dreams.

Examining Nonpharmacologic Options

In addition to pharmacotherapy, some nonpharmacologic treatments may improve function in spinocerebellar ataxia. In one double-blind trial, researchers randomized participants with various ataxias to a single session of transcranial magnetic stimulation (TMS) or sham stimulation. TMS was associated with improvement in SARA score and cerebellar motor function at 21 days. “Harvard just finished a TMS study, and we are waiting for results from that,” said Dr. Zesiewicz.

“Physical therapy is vital for patients with spinocerebellar ataxia,” she continued. One study indicated that intensive exercises such as core strength training, stepping, and dynamic balance yielded significant increases in the Berg Balance Scale. In another randomized controlled trial, four weeks of physical and occupational therapy were associated with a three-point decrease in SARA score. In addition, patients with spinocerebellar ataxia had a two-point decrease in ICARS score after undergoing four weeks of intensive cycling.

A Search for Future Therapies

Investigations of new potential treatments for spinocerebellar ataxia are ongoing. Researchers published the results of a phase II study of IV trehalose in January. Participants’ SARA score remained stable after six months of treatment.

Mesenchymal stem cells may one day provide benefits for patients. After one month of treatment with mesenchymal stromal cells, study participants with spinocerebellar ataxia had improved walking, standing, slow movement, and fine movements. Patients returned to their pretreatment condition after a few months, however.

In addition, screens of small molecules may reveal possible new therapies. One such screen identified aripiprazole as a candidate, and the drug increased longevity in a Drosophila model of Machado-Joseph disease.

“We are looking for great things. We are looking for a cure. But we will use what we have now,” Dr. Zesiewicz concluded.

—Erik Greb

Suggested Reading

Lei LF, Yang GP, Wang JL, et al. Safety and efficacy of valproic acid treatment in SCA3/MJD patients. Parkinsonism Relat Disord. 2016;26:55-61.

Ristori G, Romano S, Visconti A, et al. Riluzole in cerebellar ataxia: a randomized, double-blind, placebo-controlled pilot trial. Neurology. 2010;74(10):839-845.

Romano S, Coarelli G, Marcotulli C, et al. Riluzole in patients with hereditary cerebellar ataxia: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2015;14(10):985-891.

Strupp M, Kalla R, Claassen J, et al. A randomized trial of 4-aminopyridine in EA2 and related familial episodic ataxias. Neurology. 2011;77(3):269-275.

Zesiewicz TA, Greenstein PE, Sullivan KL, et al. A randomized trial of varenicline (Chantix) for the treatment of spinocerebellar ataxia type 3. Neurology. 2012;78(8):545-550.

NEW ORLEANS—A single bout of treadmill walking might affect cognitive processing to a greater degree than stationary cycling, particularly among those with multiple sclerosis (MS) who demonstrate low aerobic fitness, according to a report presented at the 31st Annual Meeting of the Consortium of MS Centers. "This [finding] highlights the importance of targeting those with low aerobic fitness in treadmill walking exercise training interventions for improving cognition in persons with MS, as improving aerobic fitness may be beneficial for reducing MS-related cognitive-motor interference," said Brian M. Sandroff, PhD, of the Kessler Foundation in West Orange, New Jersey, and colleagues.

The mechanisms by which treadmill walking improves cognition in patients with MS are not well understood. Researchers have hypothesized that treadmill walking is essentially a complex cognitive task that requires more attentional resources than other modalities of aerobic exercise (eg, cycle ergometry), and that repeated exposure trains the person in cognitive-motor processing. If this hypothesis is true, then patients with MS should demonstrate worse cognitive performance during treadmill walking than during cycle ergometry, as more attentional resources would presumably be devoted to walking on a treadmill than to cycling on a stationary bicycle. Furthermore, it is unknown whether better aerobic fitness attenuates such cognitive-motor interference in patients with MS.  

Dr. Sandroff and colleagues conducted a pilot study to examine cognitive performance before and during acute bouts of treadmill walking, stationary cycling, and seated quiet rest in 12 fully ambulatory patients with MS with high or low aerobic fitness using a within-subjects, repeated-measures design.  

Participants underwent a baseline incremental exercise test to exhaustion for measurement of aerobic fitness (ie, VO_2peak). Participants further completed three experimental conditions that consisted of 20 minutes of moderate- to vigorous-intensity treadmill walking exercise, moderate- to vigorous-intensity cycle ergometer exercise, and seated quiet rest in a randomized, counterbalanced order. Participants underwent the three-second Paced Auditory Serial Addition Test (PASAT) as a measure of cognitive performance prior to and during each condition.  

Overall, decreases in PASAT performance during treadmill walking were not larger than those during cycle ergometry, relative to quiet rest. However, decreases in PASAT performance were larger for those with lower aerobic fitness during treadmill walking than during cycle ergometry, compared with quiet rest.

NEW ORLEANS—A single bout of treadmill walking might affect cognitive processing to a greater degree than stationary cycling, particularly among those with multiple sclerosis (MS) who demonstrate low aerobic fitness, according to a report presented at the 31st Annual Meeting of the Consortium of MS Centers. "This [finding] highlights the importance of targeting those with low aerobic fitness in treadmill walking exercise training interventions for improving cognition in persons with MS, as improving aerobic fitness may be beneficial for reducing MS-related cognitive-motor interference," said Brian M. Sandroff, PhD, of the Kessler Foundation in West Orange, New Jersey, and colleagues.

The mechanisms by which treadmill walking improves cognition in patients with MS are not well understood. Researchers have hypothesized that treadmill walking is essentially a complex cognitive task that requires more attentional resources than other modalities of aerobic exercise (eg, cycle ergometry), and that repeated exposure trains the person in cognitive-motor processing. If this hypothesis is true, then patients with MS should demonstrate worse cognitive performance during treadmill walking than during cycle ergometry, as more attentional resources would presumably be devoted to walking on a treadmill than to cycling on a stationary bicycle. Furthermore, it is unknown whether better aerobic fitness attenuates such cognitive-motor interference in patients with MS.  

Dr. Sandroff and colleagues conducted a pilot study to examine cognitive performance before and during acute bouts of treadmill walking, stationary cycling, and seated quiet rest in 12 fully ambulatory patients with MS with high or low aerobic fitness using a within-subjects, repeated-measures design.  

Participants underwent a baseline incremental exercise test to exhaustion for measurement of aerobic fitness (ie, VO_2peak). Participants further completed three experimental conditions that consisted of 20 minutes of moderate- to vigorous-intensity treadmill walking exercise, moderate- to vigorous-intensity cycle ergometer exercise, and seated quiet rest in a randomized, counterbalanced order. Participants underwent the three-second Paced Auditory Serial Addition Test (PASAT) as a measure of cognitive performance prior to and during each condition.  

Overall, decreases in PASAT performance during treadmill walking were not larger than those during cycle ergometry, relative to quiet rest. However, decreases in PASAT performance were larger for those with lower aerobic fitness during treadmill walking than during cycle ergometry, compared with quiet rest.

NEW ORLEANS—A single bout of treadmill walking might affect cognitive processing to a greater degree than stationary cycling, particularly among those with multiple sclerosis (MS) who demonstrate low aerobic fitness, according to a report presented at the 31st Annual Meeting of the Consortium of MS Centers. "This [finding] highlights the importance of targeting those with low aerobic fitness in treadmill walking exercise training interventions for improving cognition in persons with MS, as improving aerobic fitness may be beneficial for reducing MS-related cognitive-motor interference," said Brian M. Sandroff, PhD, of the Kessler Foundation in West Orange, New Jersey, and colleagues.

The mechanisms by which treadmill walking improves cognition in patients with MS are not well understood. Researchers have hypothesized that treadmill walking is essentially a complex cognitive task that requires more attentional resources than other modalities of aerobic exercise (eg, cycle ergometry), and that repeated exposure trains the person in cognitive-motor processing. If this hypothesis is true, then patients with MS should demonstrate worse cognitive performance during treadmill walking than during cycle ergometry, as more attentional resources would presumably be devoted to walking on a treadmill than to cycling on a stationary bicycle. Furthermore, it is unknown whether better aerobic fitness attenuates such cognitive-motor interference in patients with MS.  

Dr. Sandroff and colleagues conducted a pilot study to examine cognitive performance before and during acute bouts of treadmill walking, stationary cycling, and seated quiet rest in 12 fully ambulatory patients with MS with high or low aerobic fitness using a within-subjects, repeated-measures design.  

Participants underwent a baseline incremental exercise test to exhaustion for measurement of aerobic fitness (ie, VO_2peak). Participants further completed three experimental conditions that consisted of 20 minutes of moderate- to vigorous-intensity treadmill walking exercise, moderate- to vigorous-intensity cycle ergometer exercise, and seated quiet rest in a randomized, counterbalanced order. Participants underwent the three-second Paced Auditory Serial Addition Test (PASAT) as a measure of cognitive performance prior to and during each condition.  

Overall, decreases in PASAT performance during treadmill walking were not larger than those during cycle ergometry, relative to quiet rest. However, decreases in PASAT performance were larger for those with lower aerobic fitness during treadmill walking than during cycle ergometry, compared with quiet rest.

A fever-monitoring patch was well tolerated in hospitalized patients undergoing stem cell transplant or intensive chemotherapy for leukemia, and alerted physicians to the presence of a fever much earlier than did standard temperature-taking procedures, according to findings from a study abstract that was published in conjunction with the annual meeting of the American Society of Clinical Oncology.

The patch can transmit data via Bluetooth to an iPad or smartphone, and it attempts to bring temperature recording in line with other vital signs. “It’s the only vital sign that’s not continuously monitored outside of the ICU,” said John Gannon, CEO of Blue Spark, which markets the TempTraq underarm patch used in the study.

The units are constructed with thin batteries that can be “printed” on to any surface. “Being disposable makes it a very usable work flow device,” said Mr. Gannon.

The researchers tested the TempTraq in 10 patients who had been admitted for stem cell transplant or high dose chemotherapy for leukemia.

In addition to wearing the patch, patients had their temperature measured in standard fashion every 4 hours. The researchers defined a temperature rise as a spike above 100.4° F. The device measured body temperature every 10 minutes (14,342 temperature measurements).

Standard of care measurement identified 23 temperature rise episodes, 21 of which were recorded by the TempTraq patch. The device caught temperature spikes much sooner than did standard of care measures – a median of 140.1 minutes earlier (range, 30-180 minutes).

All 10 patients continued to wear the patch throughout the hospital stay, with 9 of 10 reporting that the patch was comfortable and didn’t produce any skin irritation. Eight patients indicated interest in using the patch again, and 8 said they were completely satisfied with the patch.

The next step is to determine if the patch could be used successfully in an outpatient stem cell transplant setting.

The device could also be integrated directly with hospital central monitoring systems using Blue Spark’s TempTraq Connect, which is a HIPAA-compliant service supported by the Google Healthcare Cloud Platform, though this was not tested in the current study.

The TempTraq could be used to monitor patients for the onset of sepsis and allow faster interventions, according to Mr. Gannon. Also, patients who are susceptible to infections could be sent home with a TempTraq monitor, which would send signals to a central monitoring station.

A fever-monitoring patch was well tolerated in hospitalized patients undergoing stem cell transplant or intensive chemotherapy for leukemia, and alerted physicians to the presence of a fever much earlier than did standard temperature-taking procedures, according to findings from a study abstract that was published in conjunction with the annual meeting of the American Society of Clinical Oncology.

The patch can transmit data via Bluetooth to an iPad or smartphone, and it attempts to bring temperature recording in line with other vital signs. “It’s the only vital sign that’s not continuously monitored outside of the ICU,” said John Gannon, CEO of Blue Spark, which markets the TempTraq underarm patch used in the study.

The units are constructed with thin batteries that can be “printed” on to any surface. “Being disposable makes it a very usable work flow device,” said Mr. Gannon.

The researchers tested the TempTraq in 10 patients who had been admitted for stem cell transplant or high dose chemotherapy for leukemia.

In addition to wearing the patch, patients had their temperature measured in standard fashion every 4 hours. The researchers defined a temperature rise as a spike above 100.4° F. The device measured body temperature every 10 minutes (14,342 temperature measurements).

Standard of care measurement identified 23 temperature rise episodes, 21 of which were recorded by the TempTraq patch. The device caught temperature spikes much sooner than did standard of care measures – a median of 140.1 minutes earlier (range, 30-180 minutes).

All 10 patients continued to wear the patch throughout the hospital stay, with 9 of 10 reporting that the patch was comfortable and didn’t produce any skin irritation. Eight patients indicated interest in using the patch again, and 8 said they were completely satisfied with the patch.

The next step is to determine if the patch could be used successfully in an outpatient stem cell transplant setting.

The device could also be integrated directly with hospital central monitoring systems using Blue Spark’s TempTraq Connect, which is a HIPAA-compliant service supported by the Google Healthcare Cloud Platform, though this was not tested in the current study.

The TempTraq could be used to monitor patients for the onset of sepsis and allow faster interventions, according to Mr. Gannon. Also, patients who are susceptible to infections could be sent home with a TempTraq monitor, which would send signals to a central monitoring station.

A fever-monitoring patch was well tolerated in hospitalized patients undergoing stem cell transplant or intensive chemotherapy for leukemia, and alerted physicians to the presence of a fever much earlier than did standard temperature-taking procedures, according to findings from a study abstract that was published in conjunction with the annual meeting of the American Society of Clinical Oncology.

The patch can transmit data via Bluetooth to an iPad or smartphone, and it attempts to bring temperature recording in line with other vital signs. “It’s the only vital sign that’s not continuously monitored outside of the ICU,” said John Gannon, CEO of Blue Spark, which markets the TempTraq underarm patch used in the study.

The units are constructed with thin batteries that can be “printed” on to any surface. “Being disposable makes it a very usable work flow device,” said Mr. Gannon.

The researchers tested the TempTraq in 10 patients who had been admitted for stem cell transplant or high dose chemotherapy for leukemia.

In addition to wearing the patch, patients had their temperature measured in standard fashion every 4 hours. The researchers defined a temperature rise as a spike above 100.4° F. The device measured body temperature every 10 minutes (14,342 temperature measurements).

Standard of care measurement identified 23 temperature rise episodes, 21 of which were recorded by the TempTraq patch. The device caught temperature spikes much sooner than did standard of care measures – a median of 140.1 minutes earlier (range, 30-180 minutes).

All 10 patients continued to wear the patch throughout the hospital stay, with 9 of 10 reporting that the patch was comfortable and didn’t produce any skin irritation. Eight patients indicated interest in using the patch again, and 8 said they were completely satisfied with the patch.

The next step is to determine if the patch could be used successfully in an outpatient stem cell transplant setting.

The device could also be integrated directly with hospital central monitoring systems using Blue Spark’s TempTraq Connect, which is a HIPAA-compliant service supported by the Google Healthcare Cloud Platform, though this was not tested in the current study.

The TempTraq could be used to monitor patients for the onset of sepsis and allow faster interventions, according to Mr. Gannon. Also, patients who are susceptible to infections could be sent home with a TempTraq monitor, which would send signals to a central monitoring station.

A Retrospective Chart Review

Ms. Vollmer and colleagues conducted a retrospective study to compare the discontinuation rates and efficacy of fingolimod and dimethyl fumarate to those of natalizumab. In a retrospective chart review, they identified patients with multiple sclerosis (MS) who presented to the Rocky Mountain MS Center in Aurora, Colorado. Eligible participants initiated drug therapy between January 2010 and October 2013. Patients who initiated natalizumab had to be negative for the John Cunningham virus (JCV) at baseline. Ms. Vollmer and colleagues retrospectively collected clinician-recorded data.

The study’s primary outcome was discontinuation at 24 months. Secondary outcomes included reasons for discontinuation, relapse activity, MRI activity, and a composite disease activity measure that comprised clinical relapse, contrast enhancement, and new T2 lesions on follow-up MRI. Ms. Vollmer and colleagues identified 1,302 patients who initiated insurance paperwork for natalizumab. To reduce the size of this sample, they randomly selected 800 patients, of whom 270 met the inclusion criteria. In all, 440 participants initiated paperwork for fingolimod, of whom 271 met the inclusion criteria. For dimethyl fumarate, the researchers found 592 participants who initiated the paperwork, and 342 met the inclusion criteria.

Patients receiving natalizumab were significantly younger (mean age, 39.8) than patients receiving fingolimod (42.5) or dimethyl fumarate (45.8). Furthermore, patients treated with natalizumab were more likely to be female (77.8%) than patients treated with fingolimod (72.0%) or dimethyl fumarate (69.6%). Patients receiving natalizumab also were more likely to have contrast enhancement on baseline MRI (31.2%) than were participants receiving fingolimod (24.6%) or dimethyl fumarate (14.6%). Mean disease duration was approximately 12 years for all groups.

Discontinuation and Disease Activity

The rate of discontinuation was similar for natalizumab (33.3%) and fingolimod (34.3%), but the researchers observed a significant difference between natalizumab and dimethyl fumarate (47.1%). Disease activity and adverse events were the most common reasons for discontinuation of fingolimod and dimethyl fumarate, and JCV positivity was the most common reason for discontinuation of natalizumab. Of the seven participants who discontinued natalizumab because of disease activity, five had neutralizing antibodies. Of the 20 patients who discontinued natalizumab because of adverse events, nine had rashes during infusion, eight of whom tested positive for neutralizing antibodies.

Ms. Vollmer and colleagues found no significant difference between natalizumab and fingolimod in the rate of patients with a clinical relapse (5.6% and 8.9%, respectively), but they observed a significant difference between dimethyl fumarate (12.9%) and natalizumab for this outcome. Contrast enhancement was less common among patients receiving natalizumab (6.6%), compared with fingolimod (13.1%), but there was no significant difference between natalizumab and dimethyl fumarate (10.0%).

The rate of new T2 lesions was lower with natalizumab (21.4%), compared with fingolimod (35.0%) and dimethyl fumarate (31.5%). Similarly, the composite disease activity measure was less common with natalizumab (20.7%), compared with fingolimod (34.7%) and dimethyl fumarate (33.6%). Data adjustments indicated that discontinuation was equally likely among patients receiving fingolimod and those receiving natalizumab. Patients receiving dimethyl fumarate, however, were approximately twice as likely to discontinue treatment, compared with patients receiving natalizumab.

Furthermore, patients receiving fingolimod were approximately twice as likely to discontinue treatment because of adverse events, compared with patients receiving natalizumab. Patients treated with dimethyl fumarate were approximately four times as likely to discontinue because of adverse events, compared with patients treated with natalizumab. In addition, patients were approximately twice as likely to have disease activity on fingolimod or dimethyl fumarate, compared with natalizumab.

—Erik Greb

Suggested Reading

Barbin L, Rousseau C, Jousset N, et al. Comparative efficacy of fingolimod vs natalizumab: A French multicenter observational study. Neurology. 2016;86(8):771-778.

A Retrospective Chart Review

Ms. Vollmer and colleagues conducted a retrospective study to compare the discontinuation rates and efficacy of fingolimod and dimethyl fumarate to those of natalizumab. In a retrospective chart review, they identified patients with multiple sclerosis (MS) who presented to the Rocky Mountain MS Center in Aurora, Colorado. Eligible participants initiated drug therapy between January 2010 and October 2013. Patients who initiated natalizumab had to be negative for the John Cunningham virus (JCV) at baseline. Ms. Vollmer and colleagues retrospectively collected clinician-recorded data.

The study’s primary outcome was discontinuation at 24 months. Secondary outcomes included reasons for discontinuation, relapse activity, MRI activity, and a composite disease activity measure that comprised clinical relapse, contrast enhancement, and new T2 lesions on follow-up MRI. Ms. Vollmer and colleagues identified 1,302 patients who initiated insurance paperwork for natalizumab. To reduce the size of this sample, they randomly selected 800 patients, of whom 270 met the inclusion criteria. In all, 440 participants initiated paperwork for fingolimod, of whom 271 met the inclusion criteria. For dimethyl fumarate, the researchers found 592 participants who initiated the paperwork, and 342 met the inclusion criteria.

Patients receiving natalizumab were significantly younger (mean age, 39.8) than patients receiving fingolimod (42.5) or dimethyl fumarate (45.8). Furthermore, patients treated with natalizumab were more likely to be female (77.8%) than patients treated with fingolimod (72.0%) or dimethyl fumarate (69.6%). Patients receiving natalizumab also were more likely to have contrast enhancement on baseline MRI (31.2%) than were participants receiving fingolimod (24.6%) or dimethyl fumarate (14.6%). Mean disease duration was approximately 12 years for all groups.

Discontinuation and Disease Activity

The rate of discontinuation was similar for natalizumab (33.3%) and fingolimod (34.3%), but the researchers observed a significant difference between natalizumab and dimethyl fumarate (47.1%). Disease activity and adverse events were the most common reasons for discontinuation of fingolimod and dimethyl fumarate, and JCV positivity was the most common reason for discontinuation of natalizumab. Of the seven participants who discontinued natalizumab because of disease activity, five had neutralizing antibodies. Of the 20 patients who discontinued natalizumab because of adverse events, nine had rashes during infusion, eight of whom tested positive for neutralizing antibodies.

Ms. Vollmer and colleagues found no significant difference between natalizumab and fingolimod in the rate of patients with a clinical relapse (5.6% and 8.9%, respectively), but they observed a significant difference between dimethyl fumarate (12.9%) and natalizumab for this outcome. Contrast enhancement was less common among patients receiving natalizumab (6.6%), compared with fingolimod (13.1%), but there was no significant difference between natalizumab and dimethyl fumarate (10.0%).

The rate of new T2 lesions was lower with natalizumab (21.4%), compared with fingolimod (35.0%) and dimethyl fumarate (31.5%). Similarly, the composite disease activity measure was less common with natalizumab (20.7%), compared with fingolimod (34.7%) and dimethyl fumarate (33.6%). Data adjustments indicated that discontinuation was equally likely among patients receiving fingolimod and those receiving natalizumab. Patients receiving dimethyl fumarate, however, were approximately twice as likely to discontinue treatment, compared with patients receiving natalizumab.

Furthermore, patients receiving fingolimod were approximately twice as likely to discontinue treatment because of adverse events, compared with patients receiving natalizumab. Patients treated with dimethyl fumarate were approximately four times as likely to discontinue because of adverse events, compared with patients treated with natalizumab. In addition, patients were approximately twice as likely to have disease activity on fingolimod or dimethyl fumarate, compared with natalizumab.

—Erik Greb

Suggested Reading

Barbin L, Rousseau C, Jousset N, et al. Comparative efficacy of fingolimod vs natalizumab: A French multicenter observational study. Neurology. 2016;86(8):771-778.

A Retrospective Chart Review

Ms. Vollmer and colleagues conducted a retrospective study to compare the discontinuation rates and efficacy of fingolimod and dimethyl fumarate to those of natalizumab. In a retrospective chart review, they identified patients with multiple sclerosis (MS) who presented to the Rocky Mountain MS Center in Aurora, Colorado. Eligible participants initiated drug therapy between January 2010 and October 2013. Patients who initiated natalizumab had to be negative for the John Cunningham virus (JCV) at baseline. Ms. Vollmer and colleagues retrospectively collected clinician-recorded data.

The study’s primary outcome was discontinuation at 24 months. Secondary outcomes included reasons for discontinuation, relapse activity, MRI activity, and a composite disease activity measure that comprised clinical relapse, contrast enhancement, and new T2 lesions on follow-up MRI. Ms. Vollmer and colleagues identified 1,302 patients who initiated insurance paperwork for natalizumab. To reduce the size of this sample, they randomly selected 800 patients, of whom 270 met the inclusion criteria. In all, 440 participants initiated paperwork for fingolimod, of whom 271 met the inclusion criteria. For dimethyl fumarate, the researchers found 592 participants who initiated the paperwork, and 342 met the inclusion criteria.

Patients receiving natalizumab were significantly younger (mean age, 39.8) than patients receiving fingolimod (42.5) or dimethyl fumarate (45.8). Furthermore, patients treated with natalizumab were more likely to be female (77.8%) than patients treated with fingolimod (72.0%) or dimethyl fumarate (69.6%). Patients receiving natalizumab also were more likely to have contrast enhancement on baseline MRI (31.2%) than were participants receiving fingolimod (24.6%) or dimethyl fumarate (14.6%). Mean disease duration was approximately 12 years for all groups.

Discontinuation and Disease Activity

The rate of discontinuation was similar for natalizumab (33.3%) and fingolimod (34.3%), but the researchers observed a significant difference between natalizumab and dimethyl fumarate (47.1%). Disease activity and adverse events were the most common reasons for discontinuation of fingolimod and dimethyl fumarate, and JCV positivity was the most common reason for discontinuation of natalizumab. Of the seven participants who discontinued natalizumab because of disease activity, five had neutralizing antibodies. Of the 20 patients who discontinued natalizumab because of adverse events, nine had rashes during infusion, eight of whom tested positive for neutralizing antibodies.

Ms. Vollmer and colleagues found no significant difference between natalizumab and fingolimod in the rate of patients with a clinical relapse (5.6% and 8.9%, respectively), but they observed a significant difference between dimethyl fumarate (12.9%) and natalizumab for this outcome. Contrast enhancement was less common among patients receiving natalizumab (6.6%), compared with fingolimod (13.1%), but there was no significant difference between natalizumab and dimethyl fumarate (10.0%).

The rate of new T2 lesions was lower with natalizumab (21.4%), compared with fingolimod (35.0%) and dimethyl fumarate (31.5%). Similarly, the composite disease activity measure was less common with natalizumab (20.7%), compared with fingolimod (34.7%) and dimethyl fumarate (33.6%). Data adjustments indicated that discontinuation was equally likely among patients receiving fingolimod and those receiving natalizumab. Patients receiving dimethyl fumarate, however, were approximately twice as likely to discontinue treatment, compared with patients receiving natalizumab.

Furthermore, patients receiving fingolimod were approximately twice as likely to discontinue treatment because of adverse events, compared with patients receiving natalizumab. Patients treated with dimethyl fumarate were approximately four times as likely to discontinue because of adverse events, compared with patients treated with natalizumab. In addition, patients were approximately twice as likely to have disease activity on fingolimod or dimethyl fumarate, compared with natalizumab.

—Erik Greb

Suggested Reading

Barbin L, Rousseau C, Jousset N, et al. Comparative efficacy of fingolimod vs natalizumab: A French multicenter observational study. Neurology. 2016;86(8):771-778.

Eye tracking is a noninvasive technique that may help to assess two key physiologic signs of concussion, intracranial pressure (ICP) and ocular motility dysfunction, according to a study published online ahead of print June 2 in the Journal of Neurosurgery. This technique does not require a trained examiner, pupil dilation, imaging studies, or an invasive procedure such as lumbar or ventricular puncture, the authors noted.

“With these data, we are presenting a new application for eye-tracking technology, as well as a new mechanism for assessment of elevated ICP that is noninvasive, automatable, and could potentially be performed and analyzed remotely,” said Uzma Samadani, MD, PhD, Associate Professor of Neurosurgery at the University of Minnesota in Minneapolis, and colleagues.

The boundaries of normal and elevated intracranial pressure vary between patients, said the authors. People with elevated intracranial pressure can develop abnormalities in global cerebral functioning. Elevated ICP can also affect the function of cranial nerves, which may contribute to ocular dysmotility. Dr. Samadani and colleagues assessed the impact of elevated ICP on eye-tracking sessions performed while patients watched a short film clip.

Eligible participants ranged in age from 18 to 70, were admitted to the Bellevue Hospital neurosurgical intensive care unit in New York City with vision correctable to within 20/500 bilaterally, and had denied a history of ocular dysmotility. In addition, these patients were conscious and able to communicate and to provide an ophthalmologic, medical, and neurologic history, as well as medications, drugs, and alcohol consumed within 24 hours prior to eye tracking.

Awake patients who required placement of an ICP monitor for clinical purposes underwent eye tracking while watching a 220-second continuously playing video. The investigators recorded pupil position at 500 Hz and calculated metrics associated with each eye individually and both eyes together. In addition, the researchers performed linear regression with generalized estimating equations to test the association of eye-tracking metrics with changes in ICP.

The investigators performed eye tracking at ICP levels ranging from –3 mm Hg to 30 mm Hg in 23 patients (12 women, mean age 46.8) on 55 occasions. Eye-tracking measures correlating with cranial nerve function decreased linearly with increasing ICP.

Researchers also found that measures for cranial nerve VI were the most prominently affected. The area under the curve for eye-tracking metrics to discriminate between an ICP <12 mm Hg and one of ≥12 mm Hg was 0.798. To discriminate between an ICP <15 mm Hg and one of ≥15 mm Hg, the area under the curve was 0.833. Finally, to discriminate between an ICP <20 mm Hg and ≥20 mm Hg, the area under the curve was 0.889.

Overall, increasingly elevated ICP was associated with increasingly abnormal eye tracking detected while patients were watching the short film. The “technology has clinical applications for assessment of shunt malfunction, pseudotumor cerebri, concussion, and prevention of second-impact syndrome,” said Dr. Samadani and colleagues.

The major limitation of this study was the lack of continuous data in patients with higher ICP recordings, the authors said. Few patients with elevated ICP could open their eyes long enough to undergo eye tracking.

—Erica Tricarico

Suggested Reading

Kolecki R, Dammavalam V, Zahid A, et al. Elevated intracranial pressure and reversible eye-tracking changes detected while viewing a film clip. J Neurosurg. 2017 Jun 2 [Epub ahead of print].

Eye tracking is a noninvasive technique that may help to assess two key physiologic signs of concussion, intracranial pressure (ICP) and ocular motility dysfunction, according to a study published online ahead of print June 2 in the Journal of Neurosurgery. This technique does not require a trained examiner, pupil dilation, imaging studies, or an invasive procedure such as lumbar or ventricular puncture, the authors noted.

“With these data, we are presenting a new application for eye-tracking technology, as well as a new mechanism for assessment of elevated ICP that is noninvasive, automatable, and could potentially be performed and analyzed remotely,” said Uzma Samadani, MD, PhD, Associate Professor of Neurosurgery at the University of Minnesota in Minneapolis, and colleagues.

The boundaries of normal and elevated intracranial pressure vary between patients, said the authors. People with elevated intracranial pressure can develop abnormalities in global cerebral functioning. Elevated ICP can also affect the function of cranial nerves, which may contribute to ocular dysmotility. Dr. Samadani and colleagues assessed the impact of elevated ICP on eye-tracking sessions performed while patients watched a short film clip.

Eligible participants ranged in age from 18 to 70, were admitted to the Bellevue Hospital neurosurgical intensive care unit in New York City with vision correctable to within 20/500 bilaterally, and had denied a history of ocular dysmotility. In addition, these patients were conscious and able to communicate and to provide an ophthalmologic, medical, and neurologic history, as well as medications, drugs, and alcohol consumed within 24 hours prior to eye tracking.

Awake patients who required placement of an ICP monitor for clinical purposes underwent eye tracking while watching a 220-second continuously playing video. The investigators recorded pupil position at 500 Hz and calculated metrics associated with each eye individually and both eyes together. In addition, the researchers performed linear regression with generalized estimating equations to test the association of eye-tracking metrics with changes in ICP.

The investigators performed eye tracking at ICP levels ranging from –3 mm Hg to 30 mm Hg in 23 patients (12 women, mean age 46.8) on 55 occasions. Eye-tracking measures correlating with cranial nerve function decreased linearly with increasing ICP.

Researchers also found that measures for cranial nerve VI were the most prominently affected. The area under the curve for eye-tracking metrics to discriminate between an ICP <12 mm Hg and one of ≥12 mm Hg was 0.798. To discriminate between an ICP <15 mm Hg and one of ≥15 mm Hg, the area under the curve was 0.833. Finally, to discriminate between an ICP <20 mm Hg and ≥20 mm Hg, the area under the curve was 0.889.

Overall, increasingly elevated ICP was associated with increasingly abnormal eye tracking detected while patients were watching the short film. The “technology has clinical applications for assessment of shunt malfunction, pseudotumor cerebri, concussion, and prevention of second-impact syndrome,” said Dr. Samadani and colleagues.

The major limitation of this study was the lack of continuous data in patients with higher ICP recordings, the authors said. Few patients with elevated ICP could open their eyes long enough to undergo eye tracking.

—Erica Tricarico

Suggested Reading

Kolecki R, Dammavalam V, Zahid A, et al. Elevated intracranial pressure and reversible eye-tracking changes detected while viewing a film clip. J Neurosurg. 2017 Jun 2 [Epub ahead of print].

Eye tracking is a noninvasive technique that may help to assess two key physiologic signs of concussion, intracranial pressure (ICP) and ocular motility dysfunction, according to a study published online ahead of print June 2 in the Journal of Neurosurgery. This technique does not require a trained examiner, pupil dilation, imaging studies, or an invasive procedure such as lumbar or ventricular puncture, the authors noted.

“With these data, we are presenting a new application for eye-tracking technology, as well as a new mechanism for assessment of elevated ICP that is noninvasive, automatable, and could potentially be performed and analyzed remotely,” said Uzma Samadani, MD, PhD, Associate Professor of Neurosurgery at the University of Minnesota in Minneapolis, and colleagues.

The boundaries of normal and elevated intracranial pressure vary between patients, said the authors. People with elevated intracranial pressure can develop abnormalities in global cerebral functioning. Elevated ICP can also affect the function of cranial nerves, which may contribute to ocular dysmotility. Dr. Samadani and colleagues assessed the impact of elevated ICP on eye-tracking sessions performed while patients watched a short film clip.

Eligible participants ranged in age from 18 to 70, were admitted to the Bellevue Hospital neurosurgical intensive care unit in New York City with vision correctable to within 20/500 bilaterally, and had denied a history of ocular dysmotility. In addition, these patients were conscious and able to communicate and to provide an ophthalmologic, medical, and neurologic history, as well as medications, drugs, and alcohol consumed within 24 hours prior to eye tracking.

Awake patients who required placement of an ICP monitor for clinical purposes underwent eye tracking while watching a 220-second continuously playing video. The investigators recorded pupil position at 500 Hz and calculated metrics associated with each eye individually and both eyes together. In addition, the researchers performed linear regression with generalized estimating equations to test the association of eye-tracking metrics with changes in ICP.

The investigators performed eye tracking at ICP levels ranging from –3 mm Hg to 30 mm Hg in 23 patients (12 women, mean age 46.8) on 55 occasions. Eye-tracking measures correlating with cranial nerve function decreased linearly with increasing ICP.

Researchers also found that measures for cranial nerve VI were the most prominently affected. The area under the curve for eye-tracking metrics to discriminate between an ICP <12 mm Hg and one of ≥12 mm Hg was 0.798. To discriminate between an ICP <15 mm Hg and one of ≥15 mm Hg, the area under the curve was 0.833. Finally, to discriminate between an ICP <20 mm Hg and ≥20 mm Hg, the area under the curve was 0.889.

Overall, increasingly elevated ICP was associated with increasingly abnormal eye tracking detected while patients were watching the short film. The “technology has clinical applications for assessment of shunt malfunction, pseudotumor cerebri, concussion, and prevention of second-impact syndrome,” said Dr. Samadani and colleagues.

The major limitation of this study was the lack of continuous data in patients with higher ICP recordings, the authors said. Few patients with elevated ICP could open their eyes long enough to undergo eye tracking.

—Erica Tricarico

Suggested Reading

Kolecki R, Dammavalam V, Zahid A, et al. Elevated intracranial pressure and reversible eye-tracking changes detected while viewing a film clip. J Neurosurg. 2017 Jun 2 [Epub ahead of print].