Parkinson's Disease

Subcutaneous apomorphine infusion significantly reduces off time in patients with Parkinson’s disease and inadequately controlled motor fluctuations, according to data published in the September issue of Lancet Neurology. The data result from the first randomized controlled trial of apomorphine in this population.

In 1988, an open-label study indicated that apomorphine had antiparkinsonian efficacy equivalent to that of levodopa. Several uncontrolled studies have indicated that it effectively reduces off time, improves dyskinesias, and allows doses of oral levodopa to be decreased.

A Multicenter European Study

Regina Katzenschlager, MD, a neurologist at Danube Hospital in Vienna, and colleagues investigated the safety and efficacy of apomorphine infusion in a randomized, placebo-controlled, double-blind trial. They enrolled patients at 23 European hospitals who had received a diagnosis of Parkinson’s disease more than three years previously and had motor fluctuations that were inadequately controlled. Patients were randomized in equal groups to 3–8-mg/h infusions of apomorphine or saline for approximately 16 h/day. The treatment period lasted for 12 weeks. During the first four weeks, investigators adjusted the dose according to efficacy and tolerability, and the remaining eight weeks were a maintenance period.

Patients completed home diary assessments of motor status and visited the hospital for regular evaluations. The study’s primary end point was the absolute change in off time from baseline to 12 weeks, based on diary assessments. Secondary end points included response to therapy (ie, a reduction in off time of at least two hours from baseline), absolute change in on time without troublesome dyskinesia, Patient Global Impression of Change (PGIC) score, change in levodopa dose, change in motor score, and change in quality of life.

Results Were Consistent in Prespecified Subgroups

A total of 53 patients were randomized to apomorphine, and 54 patients were randomized to placebo. The mean final dose of study drug was 4.68 mg/h in the apomorphine group and 5.76 mg/h in the placebo group.

Mean reduction in off time was significantly greater at week 12 in the apomorphine group (−2.47 h/day) than among controls (−0.58 h/day). The results were consistent in sensitivity analyses. Approximately 62% of patients in the apomorphine group responded to therapy, compared with 29% of controls.

Mean on time without troublesome dyskinesia was significantly increased in the apomorphine group (2.77 h/day), compared with the placebo group (0.80 h/day). Apomorphine also improved PGIC scores significantly at 12 weeks, compared with placebo. Mean reduction in oral levodopa dose was greater in the apomorphine group, but the difference between groups was not statistically significant. Changes in motor score and quality of life were not significantly different between groups at 12 weeks.

The treatment was well tolerated, and the researchers found no unexpected safety signals. The rate of treatment-emergent adverse events was 93% in the apomorphine group and 57% among controls. The most common adverse events were skin reactions, nausea, and somnolence. Six patients had an adverse event that prompted study withdrawal; all were in the apomorphine group. Five patients in the apomorphine group had serious adverse events, including severe hypotension, myocardial infarction, and persistently abnormal hematology test results indicating mild leukopenia and moderate anemia.

“From a practical viewpoint, our study shows that some patients tolerate and receive benefit from doses exceeding the common range of hourly flow rates currently used in practice,” said the authors. “Many centers use higher flow rates than the mean dose in our study, and it is possible that the full potential of apomorphine has not been investigated here.”

How Effective Would Apomorphine Monotherapy Be?

The findings of Dr. Katzenschlager and colleagues “should help guide clinicians in making decisions about management of patients with advanced Parkinson’s disease, particularly when considering use of deep brain stimulation or intestinal infusion of levodopa–carbidopa gel,” said Peter A. LeWitt, MD, Director of the Parkinson’s Disease and Movement Disorder Program at Henry Ford Hospital in West Bloomfield, Michigan, in an accompanying editorial. “In view of its efficacy and safety profile, apomorphine infusion should be considered before embarking on other invasive therapies.”

On average, apomorphine infusion decreased off time by approximately one-third from patients’ baseline levels. “One might ask why the study did not achieve better results,” said Dr. LeWitt. A potential explanation is that impaired brain circuitry in patients with advanced Parkinson’s disease loses its long-term response to levodopa and is associated with dyskinesias and freezing of gait, he added. It also is possible that participants’ medical treatment had not been optimized at baseline.

“Despite a heavy load of levodopa and adjunctive medications (most participants in the study also received dopaminergic agonists, and inhibitors of catechol-O-methyltransferase and monoamine oxidase type B were used liberally), many patients continue to be burdened by substantial daily off time fluctuations,” said Dr. LeWitt. “A final question unanswered by this study is the effectiveness of apomorphine monotherapy, which has been previously tested in only a few studies. Future studies might investigate this question and what benefit, if any, is offered by concomitant levodopa treatment.”

—Erik Greb

Suggested Reading

Katzenschlager R, Poewe W, Rascol O, et al. Apomorphine subcutaneous infusion in patients with Parkinson’s disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2018;17(9):749-759.

LeWitt PA. At last, a randomised controlled trial of apomorphine infusion. Lancet Neurol. 2018;17(9):732-733.

Subcutaneous apomorphine infusion significantly reduces off time in patients with Parkinson’s disease and inadequately controlled motor fluctuations, according to data published in the September issue of Lancet Neurology. The data result from the first randomized controlled trial of apomorphine in this population.

In 1988, an open-label study indicated that apomorphine had antiparkinsonian efficacy equivalent to that of levodopa. Several uncontrolled studies have indicated that it effectively reduces off time, improves dyskinesias, and allows doses of oral levodopa to be decreased.

A Multicenter European Study

Regina Katzenschlager, MD, a neurologist at Danube Hospital in Vienna, and colleagues investigated the safety and efficacy of apomorphine infusion in a randomized, placebo-controlled, double-blind trial. They enrolled patients at 23 European hospitals who had received a diagnosis of Parkinson’s disease more than three years previously and had motor fluctuations that were inadequately controlled. Patients were randomized in equal groups to 3–8-mg/h infusions of apomorphine or saline for approximately 16 h/day. The treatment period lasted for 12 weeks. During the first four weeks, investigators adjusted the dose according to efficacy and tolerability, and the remaining eight weeks were a maintenance period.

Patients completed home diary assessments of motor status and visited the hospital for regular evaluations. The study’s primary end point was the absolute change in off time from baseline to 12 weeks, based on diary assessments. Secondary end points included response to therapy (ie, a reduction in off time of at least two hours from baseline), absolute change in on time without troublesome dyskinesia, Patient Global Impression of Change (PGIC) score, change in levodopa dose, change in motor score, and change in quality of life.

Results Were Consistent in Prespecified Subgroups

A total of 53 patients were randomized to apomorphine, and 54 patients were randomized to placebo. The mean final dose of study drug was 4.68 mg/h in the apomorphine group and 5.76 mg/h in the placebo group.

Mean reduction in off time was significantly greater at week 12 in the apomorphine group (−2.47 h/day) than among controls (−0.58 h/day). The results were consistent in sensitivity analyses. Approximately 62% of patients in the apomorphine group responded to therapy, compared with 29% of controls.

Mean on time without troublesome dyskinesia was significantly increased in the apomorphine group (2.77 h/day), compared with the placebo group (0.80 h/day). Apomorphine also improved PGIC scores significantly at 12 weeks, compared with placebo. Mean reduction in oral levodopa dose was greater in the apomorphine group, but the difference between groups was not statistically significant. Changes in motor score and quality of life were not significantly different between groups at 12 weeks.

The treatment was well tolerated, and the researchers found no unexpected safety signals. The rate of treatment-emergent adverse events was 93% in the apomorphine group and 57% among controls. The most common adverse events were skin reactions, nausea, and somnolence. Six patients had an adverse event that prompted study withdrawal; all were in the apomorphine group. Five patients in the apomorphine group had serious adverse events, including severe hypotension, myocardial infarction, and persistently abnormal hematology test results indicating mild leukopenia and moderate anemia.

“From a practical viewpoint, our study shows that some patients tolerate and receive benefit from doses exceeding the common range of hourly flow rates currently used in practice,” said the authors. “Many centers use higher flow rates than the mean dose in our study, and it is possible that the full potential of apomorphine has not been investigated here.”

How Effective Would Apomorphine Monotherapy Be?

The findings of Dr. Katzenschlager and colleagues “should help guide clinicians in making decisions about management of patients with advanced Parkinson’s disease, particularly when considering use of deep brain stimulation or intestinal infusion of levodopa–carbidopa gel,” said Peter A. LeWitt, MD, Director of the Parkinson’s Disease and Movement Disorder Program at Henry Ford Hospital in West Bloomfield, Michigan, in an accompanying editorial. “In view of its efficacy and safety profile, apomorphine infusion should be considered before embarking on other invasive therapies.”

On average, apomorphine infusion decreased off time by approximately one-third from patients’ baseline levels. “One might ask why the study did not achieve better results,” said Dr. LeWitt. A potential explanation is that impaired brain circuitry in patients with advanced Parkinson’s disease loses its long-term response to levodopa and is associated with dyskinesias and freezing of gait, he added. It also is possible that participants’ medical treatment had not been optimized at baseline.

“Despite a heavy load of levodopa and adjunctive medications (most participants in the study also received dopaminergic agonists, and inhibitors of catechol-O-methyltransferase and monoamine oxidase type B were used liberally), many patients continue to be burdened by substantial daily off time fluctuations,” said Dr. LeWitt. “A final question unanswered by this study is the effectiveness of apomorphine monotherapy, which has been previously tested in only a few studies. Future studies might investigate this question and what benefit, if any, is offered by concomitant levodopa treatment.”

—Erik Greb

Suggested Reading

Katzenschlager R, Poewe W, Rascol O, et al. Apomorphine subcutaneous infusion in patients with Parkinson’s disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2018;17(9):749-759.

LeWitt PA. At last, a randomised controlled trial of apomorphine infusion. Lancet Neurol. 2018;17(9):732-733.

Subcutaneous apomorphine infusion significantly reduces off time in patients with Parkinson’s disease and inadequately controlled motor fluctuations, according to data published in the September issue of Lancet Neurology. The data result from the first randomized controlled trial of apomorphine in this population.

In 1988, an open-label study indicated that apomorphine had antiparkinsonian efficacy equivalent to that of levodopa. Several uncontrolled studies have indicated that it effectively reduces off time, improves dyskinesias, and allows doses of oral levodopa to be decreased.

A Multicenter European Study

Regina Katzenschlager, MD, a neurologist at Danube Hospital in Vienna, and colleagues investigated the safety and efficacy of apomorphine infusion in a randomized, placebo-controlled, double-blind trial. They enrolled patients at 23 European hospitals who had received a diagnosis of Parkinson’s disease more than three years previously and had motor fluctuations that were inadequately controlled. Patients were randomized in equal groups to 3–8-mg/h infusions of apomorphine or saline for approximately 16 h/day. The treatment period lasted for 12 weeks. During the first four weeks, investigators adjusted the dose according to efficacy and tolerability, and the remaining eight weeks were a maintenance period.

Patients completed home diary assessments of motor status and visited the hospital for regular evaluations. The study’s primary end point was the absolute change in off time from baseline to 12 weeks, based on diary assessments. Secondary end points included response to therapy (ie, a reduction in off time of at least two hours from baseline), absolute change in on time without troublesome dyskinesia, Patient Global Impression of Change (PGIC) score, change in levodopa dose, change in motor score, and change in quality of life.

Results Were Consistent in Prespecified Subgroups

A total of 53 patients were randomized to apomorphine, and 54 patients were randomized to placebo. The mean final dose of study drug was 4.68 mg/h in the apomorphine group and 5.76 mg/h in the placebo group.

Mean reduction in off time was significantly greater at week 12 in the apomorphine group (−2.47 h/day) than among controls (−0.58 h/day). The results were consistent in sensitivity analyses. Approximately 62% of patients in the apomorphine group responded to therapy, compared with 29% of controls.

Mean on time without troublesome dyskinesia was significantly increased in the apomorphine group (2.77 h/day), compared with the placebo group (0.80 h/day). Apomorphine also improved PGIC scores significantly at 12 weeks, compared with placebo. Mean reduction in oral levodopa dose was greater in the apomorphine group, but the difference between groups was not statistically significant. Changes in motor score and quality of life were not significantly different between groups at 12 weeks.

The treatment was well tolerated, and the researchers found no unexpected safety signals. The rate of treatment-emergent adverse events was 93% in the apomorphine group and 57% among controls. The most common adverse events were skin reactions, nausea, and somnolence. Six patients had an adverse event that prompted study withdrawal; all were in the apomorphine group. Five patients in the apomorphine group had serious adverse events, including severe hypotension, myocardial infarction, and persistently abnormal hematology test results indicating mild leukopenia and moderate anemia.

“From a practical viewpoint, our study shows that some patients tolerate and receive benefit from doses exceeding the common range of hourly flow rates currently used in practice,” said the authors. “Many centers use higher flow rates than the mean dose in our study, and it is possible that the full potential of apomorphine has not been investigated here.”

How Effective Would Apomorphine Monotherapy Be?

The findings of Dr. Katzenschlager and colleagues “should help guide clinicians in making decisions about management of patients with advanced Parkinson’s disease, particularly when considering use of deep brain stimulation or intestinal infusion of levodopa–carbidopa gel,” said Peter A. LeWitt, MD, Director of the Parkinson’s Disease and Movement Disorder Program at Henry Ford Hospital in West Bloomfield, Michigan, in an accompanying editorial. “In view of its efficacy and safety profile, apomorphine infusion should be considered before embarking on other invasive therapies.”

On average, apomorphine infusion decreased off time by approximately one-third from patients’ baseline levels. “One might ask why the study did not achieve better results,” said Dr. LeWitt. A potential explanation is that impaired brain circuitry in patients with advanced Parkinson’s disease loses its long-term response to levodopa and is associated with dyskinesias and freezing of gait, he added. It also is possible that participants’ medical treatment had not been optimized at baseline.

“Despite a heavy load of levodopa and adjunctive medications (most participants in the study also received dopaminergic agonists, and inhibitors of catechol-O-methyltransferase and monoamine oxidase type B were used liberally), many patients continue to be burdened by substantial daily off time fluctuations,” said Dr. LeWitt. “A final question unanswered by this study is the effectiveness of apomorphine monotherapy, which has been previously tested in only a few studies. Future studies might investigate this question and what benefit, if any, is offered by concomitant levodopa treatment.”

—Erik Greb

Suggested Reading

Katzenschlager R, Poewe W, Rascol O, et al. Apomorphine subcutaneous infusion in patients with Parkinson’s disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2018;17(9):749-759.

LeWitt PA. At last, a randomised controlled trial of apomorphine infusion. Lancet Neurol. 2018;17(9):732-733.

HILTON HEAD, SC—When neurologists see patients remotely, the focus should be on the patient, not on the technology behind the virtual visit, according to one researcher.

“One of the big mistakes that is made with telehealth is focusing on the technology and not on the clinical care delivery,” said Kenneth Gaines, MD, Professor of Neurology at Vanderbilt University in Nashville. “It is the clinical care delivery that ought to drive the technology. Too often it happens in reverse…. That is a recipe for an ineffective program.”

Broadly speaking, telemedicine is medicine practiced at a distance. Ideally, it uses technology to facilitate a clinical care paradigm that improves efficiency, care coordination, and outcomes and lowers costs, Dr. Gaines said. The public increasingly expects this type of care to be available, he said.

“Why would telehealth be useful in neurology? In part because we deal with acute and chronic disease, which is what stroke is, for example, but also other diseases like epilepsy,” Dr. Gaines said at Vanderbilt’s 41st Annual Contemporary Clinical Neurology Symposium. In addition, neurologic diseases are complex, and generalists’ training in them may be limited. Telehealth could allow neurologists to assist general practitioners and provide neurologic care to areas with few neurologists.

Opportunity in Neurology

Systematic reviews in disease states like diabetes, hyperlipidemia, and hypertension have found that telemedicine may benefit patients. A 2015 Cochrane review of data from randomized controlled trials of interactive telemedicine found with moderate certainty that telemedicine decreased LDL and blood pressure, compared with usual care. It found with high certainty that among patients with diabetes, those who received telemedicine had lower glycated hemoglobin levels at nine months, compared with controls. Evidence to assess the effects of telemedicine in neurology, however, was inadequate.

Nevertheless, studies indicate telemedicine’s promise in neurology. Beck et al conducted the Connect.Parkinson trial, which included 195 patients with Parkinson’s disease who were randomized to usual care or usual care plus four virtual visits via video conferencing with a remote specialist. The researchers found that telemedicine was feasible and equivalent to usual care with regard to its effects on patients’ quality of life. The virtual house calls saved patients a median of 88 minutes and 38 miles per visit. Mammen et al analyzed survey data from patients with Parkinson’s disease and physicians and found that they generally were satisfied with the telemedicine approach, but technical problems affected individual experiences. Physicians’ greatest source of dissatisfaction was performing a detailed motor examination remotely.

Samii et al reported the experience of one Veterans Administration medical center that found it feasible to conduct follow-up visits with patients with Parkinson’s disease via telemedicine. Although the video quality initially was not sufficient to score the motor Unified Parkinson’s Disease Rating Scale, a videoconferencing unit upgrade allowed physicians to assess those measures, with the exception of elements that require physical contact, such as rigidity and retropulsion.

A study by Kane et al found that telemedicine assessments of patients with multiple sclerosis could reliably determine Expanded Disability Status Scale scores. Scores related to cerebellar and brainstem functions, however, were less consistent with the scores of a hands-on examiner than were scores related to optic, bowel, bladder, and cerebral functions.

In neurology, most studies of telemedicine have focused on stroke, perhaps because of the complex and time-sensitive nature of the disease and a maldistribution of health care providers, Dr. Gaines said.

The Telemedical Pilot Project for Integrative Stroke Care (TEMPiS) in Germany connected 12 community hospitals that had limited experience with stroke thrombolysis to two specialized stroke centers. In the first 22 months, patients treated at the community hospitals and at the stroke centers had equivalent rates of mortality and good functional outcomes that were similar to those in randomized trials, Schwab et al reported.

In the STRokE DOC trial, Meyer et al assessed whether telemedicine (ie, real-time, two-way audio and video communication and digital imaging interpretation) or telephone consultation was superior in acute stroke consultations. In all, 111 patients were randomized to telemedicine, and 111 were randomized to telephone consultation. Ninety-day functional outcomes and rates of intracerebral hemorrhage after treatment with thromblytics and mortality were equivalent between the groups. With telemedicine, neurologists were more likely to arrive at a correct treatment decision and less likely to violate trial protocols, Dr. Gaines said.

The Neglected First Year

Dr. Gaines helped create a comprehensive stroke care model at Ochsner Medical Center in New Orleans that incorporated telemedicine. The program targeted acute stroke treatment as well as what Dr. Gaines calls the neglected first year after hospitalization for stroke. “In the chronic phase of stroke, these folks have significant disability. It is a significant stressor for their families and their caregivers, and unfortunately we have relatively poor risk factor control and inadequate medication compliance in this segment,” he said. Patients have high death rates due to recurrent stroke, complications of stroke, and other cardiovascular diseases.

The medical center provided telemedicine consultations to 22 affiliated hospitals. In addition, a Stroke Mobile team that consisted of a nurse and a health educator visited patients’ homes monthly for one year to address stroke risks and complications. Stroke Mobile staff used HIPAA-compliant video communication to facilitate telemedicine consultations with a vascular neurologist or advanced practice clinician during the home visits.

This model decreased length of hospital stay by one day, decreased cost per case by 9%, and lowered readmission and stroke recurrence by about 17% each. Furthermore, between 85% and 90% of patients achieved control of risk factors such as blood pressure, diabetes, and cholesterol. “Projects like this can offer us a much better, more comprehensive approach,” said Dr. Gaines.

Performing Neurologic Exams Remotely

Researchers have found that the NIH Stroke Scale can be administered as reliably in a telehealth setting as in person, Dr. Gaines said. Shafqat et al found that four NIH Stroke Scale items had excellent agreement (ie, orientation, motor arm, motor leg, and neglect), and six items had good agreement (ie, language, dysarthria, sensation, visual fields, facial palsy, and gaze), whereas two items (ie, commands and ataxia) had poor agreement, when they compared remote and in-person assessments.

Certain examination elements require the assistance of a nurse or emergency department doctor who is with the patient, and a neurologist’s confidence in his or her ability to perform a neurologic examination via telehealth may depend on how much he or she is “willing to ask people to do,” Dr. Gaines said. “I will ask somebody to shine a light into the eyes so I can look at the pupils. I will have a person who is helping me in the ER setting do a Babinski sign and watch for the response. I have diagnosed a hereditary neuropathy with liability to pressure palsies via teleneurology.”

Emergency department doctors and nurses often know how to perform elements of neurologic examinations, even if they do not routinely use them. “We spend time training nurses at our sites to help us,” he said.

In addition, neurologists can assess gait, which typically is not tested in emergency rooms but can provide valuable information. A patient’s gait might help a neurologist identify cerebellar infarcts that otherwise would have been attributed to dizziness, for example.

Telemedicine presents “opportunities … to impact stroke care and hopefully other areas of neurology as well. It is not nearly as daunting as you might think to do these consults virtually,” Dr. Gaines said. “It is a great opportunity for us to put systems of care in place to deal with some of the inequities and problems with delivery that we have.”

—Jake Remaly

Suggested Reading

Beck CA, Beran DB, Biglan KM, et al. National randomized controlled trial of virtual house calls for Parkinson disease. Neurology. 2017;89(11):1152-1161.

Flodgren G, Rachas A, Farmer AJ, et al. Interactive telemedicine: effects on professional practice and health care outcomes. Cochrane Database Syst Rev. 2015;(9):CD002098.

Kane RL, Bever CT, Ehrmantraut M, et al. Teleneurology in patients with multiple sclerosis: EDSS ratings derived remotely and from hands-on examination. J Telemed Telecare. 2008;14(4):190-194.

Mammen JR, Elson MJ, Java JJ, et al. Patient and physician perceptions of virtual visits for Parkinson’s disease: a qualitative study. Telemed J E Health. 2018;24(4):255-267.

Meyer BC, Raman R, Hemmen T, et al. Efficacy of site-independent telemedicine in the STRokE DOC trial: a randomised, blinded, prospective study. Lancet Neurol. 2008;7(9):787-795.

Samii A, Ryan-Dykes P, Tsukuda RA, et al. Telemedicine for delivery of health care in Parkinson’s disease. J Telemed Telecare. 2006;12(1):16-18.

Schwab S, Vatankhah B, Kukla C, et al. Long-term outcome after thrombolysis in telemedical stroke care. Neurology. 2007;69(9):898-903.

Shafqat S, Kvedar JC, Guanci MM, et al. Role for telemedicine in acute stroke. Feasibility and reliability of remote administration of the NIH stroke scale. Stroke. 1999;30(10):2141-2145.

HILTON HEAD, SC—When neurologists see patients remotely, the focus should be on the patient, not on the technology behind the virtual visit, according to one researcher.

“One of the big mistakes that is made with telehealth is focusing on the technology and not on the clinical care delivery,” said Kenneth Gaines, MD, Professor of Neurology at Vanderbilt University in Nashville. “It is the clinical care delivery that ought to drive the technology. Too often it happens in reverse…. That is a recipe for an ineffective program.”

Broadly speaking, telemedicine is medicine practiced at a distance. Ideally, it uses technology to facilitate a clinical care paradigm that improves efficiency, care coordination, and outcomes and lowers costs, Dr. Gaines said. The public increasingly expects this type of care to be available, he said.

“Why would telehealth be useful in neurology? In part because we deal with acute and chronic disease, which is what stroke is, for example, but also other diseases like epilepsy,” Dr. Gaines said at Vanderbilt’s 41st Annual Contemporary Clinical Neurology Symposium. In addition, neurologic diseases are complex, and generalists’ training in them may be limited. Telehealth could allow neurologists to assist general practitioners and provide neurologic care to areas with few neurologists.

Opportunity in Neurology

Systematic reviews in disease states like diabetes, hyperlipidemia, and hypertension have found that telemedicine may benefit patients. A 2015 Cochrane review of data from randomized controlled trials of interactive telemedicine found with moderate certainty that telemedicine decreased LDL and blood pressure, compared with usual care. It found with high certainty that among patients with diabetes, those who received telemedicine had lower glycated hemoglobin levels at nine months, compared with controls. Evidence to assess the effects of telemedicine in neurology, however, was inadequate.

Nevertheless, studies indicate telemedicine’s promise in neurology. Beck et al conducted the Connect.Parkinson trial, which included 195 patients with Parkinson’s disease who were randomized to usual care or usual care plus four virtual visits via video conferencing with a remote specialist. The researchers found that telemedicine was feasible and equivalent to usual care with regard to its effects on patients’ quality of life. The virtual house calls saved patients a median of 88 minutes and 38 miles per visit. Mammen et al analyzed survey data from patients with Parkinson’s disease and physicians and found that they generally were satisfied with the telemedicine approach, but technical problems affected individual experiences. Physicians’ greatest source of dissatisfaction was performing a detailed motor examination remotely.

Samii et al reported the experience of one Veterans Administration medical center that found it feasible to conduct follow-up visits with patients with Parkinson’s disease via telemedicine. Although the video quality initially was not sufficient to score the motor Unified Parkinson’s Disease Rating Scale, a videoconferencing unit upgrade allowed physicians to assess those measures, with the exception of elements that require physical contact, such as rigidity and retropulsion.

A study by Kane et al found that telemedicine assessments of patients with multiple sclerosis could reliably determine Expanded Disability Status Scale scores. Scores related to cerebellar and brainstem functions, however, were less consistent with the scores of a hands-on examiner than were scores related to optic, bowel, bladder, and cerebral functions.

In neurology, most studies of telemedicine have focused on stroke, perhaps because of the complex and time-sensitive nature of the disease and a maldistribution of health care providers, Dr. Gaines said.

The Telemedical Pilot Project for Integrative Stroke Care (TEMPiS) in Germany connected 12 community hospitals that had limited experience with stroke thrombolysis to two specialized stroke centers. In the first 22 months, patients treated at the community hospitals and at the stroke centers had equivalent rates of mortality and good functional outcomes that were similar to those in randomized trials, Schwab et al reported.

In the STRokE DOC trial, Meyer et al assessed whether telemedicine (ie, real-time, two-way audio and video communication and digital imaging interpretation) or telephone consultation was superior in acute stroke consultations. In all, 111 patients were randomized to telemedicine, and 111 were randomized to telephone consultation. Ninety-day functional outcomes and rates of intracerebral hemorrhage after treatment with thromblytics and mortality were equivalent between the groups. With telemedicine, neurologists were more likely to arrive at a correct treatment decision and less likely to violate trial protocols, Dr. Gaines said.

The Neglected First Year

Dr. Gaines helped create a comprehensive stroke care model at Ochsner Medical Center in New Orleans that incorporated telemedicine. The program targeted acute stroke treatment as well as what Dr. Gaines calls the neglected first year after hospitalization for stroke. “In the chronic phase of stroke, these folks have significant disability. It is a significant stressor for their families and their caregivers, and unfortunately we have relatively poor risk factor control and inadequate medication compliance in this segment,” he said. Patients have high death rates due to recurrent stroke, complications of stroke, and other cardiovascular diseases.

The medical center provided telemedicine consultations to 22 affiliated hospitals. In addition, a Stroke Mobile team that consisted of a nurse and a health educator visited patients’ homes monthly for one year to address stroke risks and complications. Stroke Mobile staff used HIPAA-compliant video communication to facilitate telemedicine consultations with a vascular neurologist or advanced practice clinician during the home visits.

This model decreased length of hospital stay by one day, decreased cost per case by 9%, and lowered readmission and stroke recurrence by about 17% each. Furthermore, between 85% and 90% of patients achieved control of risk factors such as blood pressure, diabetes, and cholesterol. “Projects like this can offer us a much better, more comprehensive approach,” said Dr. Gaines.

Performing Neurologic Exams Remotely

Researchers have found that the NIH Stroke Scale can be administered as reliably in a telehealth setting as in person, Dr. Gaines said. Shafqat et al found that four NIH Stroke Scale items had excellent agreement (ie, orientation, motor arm, motor leg, and neglect), and six items had good agreement (ie, language, dysarthria, sensation, visual fields, facial palsy, and gaze), whereas two items (ie, commands and ataxia) had poor agreement, when they compared remote and in-person assessments.

Certain examination elements require the assistance of a nurse or emergency department doctor who is with the patient, and a neurologist’s confidence in his or her ability to perform a neurologic examination via telehealth may depend on how much he or she is “willing to ask people to do,” Dr. Gaines said. “I will ask somebody to shine a light into the eyes so I can look at the pupils. I will have a person who is helping me in the ER setting do a Babinski sign and watch for the response. I have diagnosed a hereditary neuropathy with liability to pressure palsies via teleneurology.”

Emergency department doctors and nurses often know how to perform elements of neurologic examinations, even if they do not routinely use them. “We spend time training nurses at our sites to help us,” he said.

In addition, neurologists can assess gait, which typically is not tested in emergency rooms but can provide valuable information. A patient’s gait might help a neurologist identify cerebellar infarcts that otherwise would have been attributed to dizziness, for example.

Telemedicine presents “opportunities … to impact stroke care and hopefully other areas of neurology as well. It is not nearly as daunting as you might think to do these consults virtually,” Dr. Gaines said. “It is a great opportunity for us to put systems of care in place to deal with some of the inequities and problems with delivery that we have.”

—Jake Remaly

Suggested Reading

Beck CA, Beran DB, Biglan KM, et al. National randomized controlled trial of virtual house calls for Parkinson disease. Neurology. 2017;89(11):1152-1161.

Flodgren G, Rachas A, Farmer AJ, et al. Interactive telemedicine: effects on professional practice and health care outcomes. Cochrane Database Syst Rev. 2015;(9):CD002098.

Kane RL, Bever CT, Ehrmantraut M, et al. Teleneurology in patients with multiple sclerosis: EDSS ratings derived remotely and from hands-on examination. J Telemed Telecare. 2008;14(4):190-194.

Mammen JR, Elson MJ, Java JJ, et al. Patient and physician perceptions of virtual visits for Parkinson’s disease: a qualitative study. Telemed J E Health. 2018;24(4):255-267.

Meyer BC, Raman R, Hemmen T, et al. Efficacy of site-independent telemedicine in the STRokE DOC trial: a randomised, blinded, prospective study. Lancet Neurol. 2008;7(9):787-795.

Samii A, Ryan-Dykes P, Tsukuda RA, et al. Telemedicine for delivery of health care in Parkinson’s disease. J Telemed Telecare. 2006;12(1):16-18.

Schwab S, Vatankhah B, Kukla C, et al. Long-term outcome after thrombolysis in telemedical stroke care. Neurology. 2007;69(9):898-903.

Shafqat S, Kvedar JC, Guanci MM, et al. Role for telemedicine in acute stroke. Feasibility and reliability of remote administration of the NIH stroke scale. Stroke. 1999;30(10):2141-2145.

HILTON HEAD, SC—When neurologists see patients remotely, the focus should be on the patient, not on the technology behind the virtual visit, according to one researcher.

“One of the big mistakes that is made with telehealth is focusing on the technology and not on the clinical care delivery,” said Kenneth Gaines, MD, Professor of Neurology at Vanderbilt University in Nashville. “It is the clinical care delivery that ought to drive the technology. Too often it happens in reverse…. That is a recipe for an ineffective program.”

Broadly speaking, telemedicine is medicine practiced at a distance. Ideally, it uses technology to facilitate a clinical care paradigm that improves efficiency, care coordination, and outcomes and lowers costs, Dr. Gaines said. The public increasingly expects this type of care to be available, he said.

“Why would telehealth be useful in neurology? In part because we deal with acute and chronic disease, which is what stroke is, for example, but also other diseases like epilepsy,” Dr. Gaines said at Vanderbilt’s 41st Annual Contemporary Clinical Neurology Symposium. In addition, neurologic diseases are complex, and generalists’ training in them may be limited. Telehealth could allow neurologists to assist general practitioners and provide neurologic care to areas with few neurologists.

Opportunity in Neurology

Systematic reviews in disease states like diabetes, hyperlipidemia, and hypertension have found that telemedicine may benefit patients. A 2015 Cochrane review of data from randomized controlled trials of interactive telemedicine found with moderate certainty that telemedicine decreased LDL and blood pressure, compared with usual care. It found with high certainty that among patients with diabetes, those who received telemedicine had lower glycated hemoglobin levels at nine months, compared with controls. Evidence to assess the effects of telemedicine in neurology, however, was inadequate.

Nevertheless, studies indicate telemedicine’s promise in neurology. Beck et al conducted the Connect.Parkinson trial, which included 195 patients with Parkinson’s disease who were randomized to usual care or usual care plus four virtual visits via video conferencing with a remote specialist. The researchers found that telemedicine was feasible and equivalent to usual care with regard to its effects on patients’ quality of life. The virtual house calls saved patients a median of 88 minutes and 38 miles per visit. Mammen et al analyzed survey data from patients with Parkinson’s disease and physicians and found that they generally were satisfied with the telemedicine approach, but technical problems affected individual experiences. Physicians’ greatest source of dissatisfaction was performing a detailed motor examination remotely.

Samii et al reported the experience of one Veterans Administration medical center that found it feasible to conduct follow-up visits with patients with Parkinson’s disease via telemedicine. Although the video quality initially was not sufficient to score the motor Unified Parkinson’s Disease Rating Scale, a videoconferencing unit upgrade allowed physicians to assess those measures, with the exception of elements that require physical contact, such as rigidity and retropulsion.

A study by Kane et al found that telemedicine assessments of patients with multiple sclerosis could reliably determine Expanded Disability Status Scale scores. Scores related to cerebellar and brainstem functions, however, were less consistent with the scores of a hands-on examiner than were scores related to optic, bowel, bladder, and cerebral functions.

In neurology, most studies of telemedicine have focused on stroke, perhaps because of the complex and time-sensitive nature of the disease and a maldistribution of health care providers, Dr. Gaines said.

The Telemedical Pilot Project for Integrative Stroke Care (TEMPiS) in Germany connected 12 community hospitals that had limited experience with stroke thrombolysis to two specialized stroke centers. In the first 22 months, patients treated at the community hospitals and at the stroke centers had equivalent rates of mortality and good functional outcomes that were similar to those in randomized trials, Schwab et al reported.

In the STRokE DOC trial, Meyer et al assessed whether telemedicine (ie, real-time, two-way audio and video communication and digital imaging interpretation) or telephone consultation was superior in acute stroke consultations. In all, 111 patients were randomized to telemedicine, and 111 were randomized to telephone consultation. Ninety-day functional outcomes and rates of intracerebral hemorrhage after treatment with thromblytics and mortality were equivalent between the groups. With telemedicine, neurologists were more likely to arrive at a correct treatment decision and less likely to violate trial protocols, Dr. Gaines said.

The Neglected First Year

Dr. Gaines helped create a comprehensive stroke care model at Ochsner Medical Center in New Orleans that incorporated telemedicine. The program targeted acute stroke treatment as well as what Dr. Gaines calls the neglected first year after hospitalization for stroke. “In the chronic phase of stroke, these folks have significant disability. It is a significant stressor for their families and their caregivers, and unfortunately we have relatively poor risk factor control and inadequate medication compliance in this segment,” he said. Patients have high death rates due to recurrent stroke, complications of stroke, and other cardiovascular diseases.

The medical center provided telemedicine consultations to 22 affiliated hospitals. In addition, a Stroke Mobile team that consisted of a nurse and a health educator visited patients’ homes monthly for one year to address stroke risks and complications. Stroke Mobile staff used HIPAA-compliant video communication to facilitate telemedicine consultations with a vascular neurologist or advanced practice clinician during the home visits.

This model decreased length of hospital stay by one day, decreased cost per case by 9%, and lowered readmission and stroke recurrence by about 17% each. Furthermore, between 85% and 90% of patients achieved control of risk factors such as blood pressure, diabetes, and cholesterol. “Projects like this can offer us a much better, more comprehensive approach,” said Dr. Gaines.

Performing Neurologic Exams Remotely

Researchers have found that the NIH Stroke Scale can be administered as reliably in a telehealth setting as in person, Dr. Gaines said. Shafqat et al found that four NIH Stroke Scale items had excellent agreement (ie, orientation, motor arm, motor leg, and neglect), and six items had good agreement (ie, language, dysarthria, sensation, visual fields, facial palsy, and gaze), whereas two items (ie, commands and ataxia) had poor agreement, when they compared remote and in-person assessments.

Certain examination elements require the assistance of a nurse or emergency department doctor who is with the patient, and a neurologist’s confidence in his or her ability to perform a neurologic examination via telehealth may depend on how much he or she is “willing to ask people to do,” Dr. Gaines said. “I will ask somebody to shine a light into the eyes so I can look at the pupils. I will have a person who is helping me in the ER setting do a Babinski sign and watch for the response. I have diagnosed a hereditary neuropathy with liability to pressure palsies via teleneurology.”

Emergency department doctors and nurses often know how to perform elements of neurologic examinations, even if they do not routinely use them. “We spend time training nurses at our sites to help us,” he said.

In addition, neurologists can assess gait, which typically is not tested in emergency rooms but can provide valuable information. A patient’s gait might help a neurologist identify cerebellar infarcts that otherwise would have been attributed to dizziness, for example.

Telemedicine presents “opportunities … to impact stroke care and hopefully other areas of neurology as well. It is not nearly as daunting as you might think to do these consults virtually,” Dr. Gaines said. “It is a great opportunity for us to put systems of care in place to deal with some of the inequities and problems with delivery that we have.”

—Jake Remaly

Suggested Reading

Beck CA, Beran DB, Biglan KM, et al. National randomized controlled trial of virtual house calls for Parkinson disease. Neurology. 2017;89(11):1152-1161.

Flodgren G, Rachas A, Farmer AJ, et al. Interactive telemedicine: effects on professional practice and health care outcomes. Cochrane Database Syst Rev. 2015;(9):CD002098.

Kane RL, Bever CT, Ehrmantraut M, et al. Teleneurology in patients with multiple sclerosis: EDSS ratings derived remotely and from hands-on examination. J Telemed Telecare. 2008;14(4):190-194.

Mammen JR, Elson MJ, Java JJ, et al. Patient and physician perceptions of virtual visits for Parkinson’s disease: a qualitative study. Telemed J E Health. 2018;24(4):255-267.

Meyer BC, Raman R, Hemmen T, et al. Efficacy of site-independent telemedicine in the STRokE DOC trial: a randomised, blinded, prospective study. Lancet Neurol. 2008;7(9):787-795.

Samii A, Ryan-Dykes P, Tsukuda RA, et al. Telemedicine for delivery of health care in Parkinson’s disease. J Telemed Telecare. 2006;12(1):16-18.

Schwab S, Vatankhah B, Kukla C, et al. Long-term outcome after thrombolysis in telemedical stroke care. Neurology. 2007;69(9):898-903.

Shafqat S, Kvedar JC, Guanci MM, et al. Role for telemedicine in acute stroke. Feasibility and reliability of remote administration of the NIH stroke scale. Stroke. 1999;30(10):2141-2145.

MIAMI—As a treatment for Parkinson’s disease psychosis, pimavanserin is associated with significantly improved outcomes, compared with quetiapine and other therapies, according to research presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. “The data suggest that use of pimavanserin is associated with significantly improved treatment outcomes, both within and beyond six months of treatment,” said Conrad Tenenbaum, PhD, Senior Associate at BluePrint Research Group in Princeton, New Jersey, and colleagues.

More than half of patients with Parkinson’s disease develop related psychosis. According to Dr. Tenenbaum and colleagues, most clinicians prescribe quetiapine for Parkinson’s disease psychosis, but clinicians report that pimavanserin is more likely to provide adequate control of symptoms. To probe this discrepancy, Dr. Tenenbaum and colleagues investigated current treatments and outcomes for patients with Parkinson’s disease psychosis to improve disease management.

A Retrospective Chart Review

The researchers collected 1,800 anonymized patient charts from 200 physicians who each managed at least eight pharmacologically treated patients with Parkinson’s disease psychosis during the previous six months. Each physician contributed abbreviated charts for his or her six most recently treated patients. The charts contained information about demographics, symptoms, and treatment. The physicians also provided three detailed charts that included expanded demographic information, full treatment history, and physician-rated control of symptoms. The investigators weighted the data by physician specialty and volume of patients with Parkinson’s disease psychosis.

Of the participating physicians, 101 were neurologists, 46 were movement disorder specialists, 38 were psychiatrists, and 15 were geriatric psychiatrists. The physicians provided 1,200 abbreviated charts and 600 detailed charts.

More Than Half of Patients Received Quetiapine

Approximately 90% of treated patients with Parkinson’s disease psychosis received an antipsychotic agent as first-line therapy. More than 50% of treated patients received quetiapine, 18% received pimavanserin, and 31% received another antipsychotic or other type of treatment (eg, an antidepressant or antidementia agent). Among patients who received quetiapine as a first-line therapy, 68% received a low dose (ie, less than 100 mg/day), and 32% received a high dose (ie, more than 100 mg/day). The discontinuation rate was 15% for quetiapine and 1% for pimavanserin.

The participating physicians reported that the symptoms of Parkinson’s disease psychosis were significantly better controlled among patients treated with 34 mg of pimavanserin, compared with a low dose of quetiapine. About 60% of patients treated with pimavanserin achieved adequate symptom control within six months of treatment, compared with 38% of patients receiving low-dose quetiapine. Patients who received pimavanserin for more than six months achieved significantly better symptom control than patients who received any dose of quetiapine.

“Despite the widespread use of quetiapine as a first-line treatment of Parkinson’s disease psychosis, we find that patients treated with 34 mg of pimavanserin achieve significantly better physician-reported control of … symptoms, especially compared with those who receive low-dose quetiapine,” said Dr. Tenenbaum and colleagues. “Increased use of 34 mg of pimavanserin as a first-line pharmacologic treatment for Parkinson’s disease psychosis is suggested to improve outcomes and overall control of symptoms.”

The group of investigators included Doral Fredericks, PharmD, Vice President of Medical Affairs at Acadia Pharmaceuticals in San Diego. Acadia Pharmaceuticals markets Nuplazid, a formulation of pimavanserin.

—Erik Greb

Suggested Reading

Forsaa EB, Larsen JP, Wentzel-Larsen T, et al. A 12-year population-based study of psychosis in Parkinson disease. Arch Neurol. 2010;67(8):996-1001.

MIAMI—As a treatment for Parkinson’s disease psychosis, pimavanserin is associated with significantly improved outcomes, compared with quetiapine and other therapies, according to research presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. “The data suggest that use of pimavanserin is associated with significantly improved treatment outcomes, both within and beyond six months of treatment,” said Conrad Tenenbaum, PhD, Senior Associate at BluePrint Research Group in Princeton, New Jersey, and colleagues.

More than half of patients with Parkinson’s disease develop related psychosis. According to Dr. Tenenbaum and colleagues, most clinicians prescribe quetiapine for Parkinson’s disease psychosis, but clinicians report that pimavanserin is more likely to provide adequate control of symptoms. To probe this discrepancy, Dr. Tenenbaum and colleagues investigated current treatments and outcomes for patients with Parkinson’s disease psychosis to improve disease management.

A Retrospective Chart Review

The researchers collected 1,800 anonymized patient charts from 200 physicians who each managed at least eight pharmacologically treated patients with Parkinson’s disease psychosis during the previous six months. Each physician contributed abbreviated charts for his or her six most recently treated patients. The charts contained information about demographics, symptoms, and treatment. The physicians also provided three detailed charts that included expanded demographic information, full treatment history, and physician-rated control of symptoms. The investigators weighted the data by physician specialty and volume of patients with Parkinson’s disease psychosis.

Of the participating physicians, 101 were neurologists, 46 were movement disorder specialists, 38 were psychiatrists, and 15 were geriatric psychiatrists. The physicians provided 1,200 abbreviated charts and 600 detailed charts.

More Than Half of Patients Received Quetiapine

Approximately 90% of treated patients with Parkinson’s disease psychosis received an antipsychotic agent as first-line therapy. More than 50% of treated patients received quetiapine, 18% received pimavanserin, and 31% received another antipsychotic or other type of treatment (eg, an antidepressant or antidementia agent). Among patients who received quetiapine as a first-line therapy, 68% received a low dose (ie, less than 100 mg/day), and 32% received a high dose (ie, more than 100 mg/day). The discontinuation rate was 15% for quetiapine and 1% for pimavanserin.

The participating physicians reported that the symptoms of Parkinson’s disease psychosis were significantly better controlled among patients treated with 34 mg of pimavanserin, compared with a low dose of quetiapine. About 60% of patients treated with pimavanserin achieved adequate symptom control within six months of treatment, compared with 38% of patients receiving low-dose quetiapine. Patients who received pimavanserin for more than six months achieved significantly better symptom control than patients who received any dose of quetiapine.

“Despite the widespread use of quetiapine as a first-line treatment of Parkinson’s disease psychosis, we find that patients treated with 34 mg of pimavanserin achieve significantly better physician-reported control of … symptoms, especially compared with those who receive low-dose quetiapine,” said Dr. Tenenbaum and colleagues. “Increased use of 34 mg of pimavanserin as a first-line pharmacologic treatment for Parkinson’s disease psychosis is suggested to improve outcomes and overall control of symptoms.”

The group of investigators included Doral Fredericks, PharmD, Vice President of Medical Affairs at Acadia Pharmaceuticals in San Diego. Acadia Pharmaceuticals markets Nuplazid, a formulation of pimavanserin.

—Erik Greb

Suggested Reading

Forsaa EB, Larsen JP, Wentzel-Larsen T, et al. A 12-year population-based study of psychosis in Parkinson disease. Arch Neurol. 2010;67(8):996-1001.

MIAMI—As a treatment for Parkinson’s disease psychosis, pimavanserin is associated with significantly improved outcomes, compared with quetiapine and other therapies, according to research presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. “The data suggest that use of pimavanserin is associated with significantly improved treatment outcomes, both within and beyond six months of treatment,” said Conrad Tenenbaum, PhD, Senior Associate at BluePrint Research Group in Princeton, New Jersey, and colleagues.

More than half of patients with Parkinson’s disease develop related psychosis. According to Dr. Tenenbaum and colleagues, most clinicians prescribe quetiapine for Parkinson’s disease psychosis, but clinicians report that pimavanserin is more likely to provide adequate control of symptoms. To probe this discrepancy, Dr. Tenenbaum and colleagues investigated current treatments and outcomes for patients with Parkinson’s disease psychosis to improve disease management.

A Retrospective Chart Review

The researchers collected 1,800 anonymized patient charts from 200 physicians who each managed at least eight pharmacologically treated patients with Parkinson’s disease psychosis during the previous six months. Each physician contributed abbreviated charts for his or her six most recently treated patients. The charts contained information about demographics, symptoms, and treatment. The physicians also provided three detailed charts that included expanded demographic information, full treatment history, and physician-rated control of symptoms. The investigators weighted the data by physician specialty and volume of patients with Parkinson’s disease psychosis.

Of the participating physicians, 101 were neurologists, 46 were movement disorder specialists, 38 were psychiatrists, and 15 were geriatric psychiatrists. The physicians provided 1,200 abbreviated charts and 600 detailed charts.

More Than Half of Patients Received Quetiapine

Approximately 90% of treated patients with Parkinson’s disease psychosis received an antipsychotic agent as first-line therapy. More than 50% of treated patients received quetiapine, 18% received pimavanserin, and 31% received another antipsychotic or other type of treatment (eg, an antidepressant or antidementia agent). Among patients who received quetiapine as a first-line therapy, 68% received a low dose (ie, less than 100 mg/day), and 32% received a high dose (ie, more than 100 mg/day). The discontinuation rate was 15% for quetiapine and 1% for pimavanserin.

The participating physicians reported that the symptoms of Parkinson’s disease psychosis were significantly better controlled among patients treated with 34 mg of pimavanserin, compared with a low dose of quetiapine. About 60% of patients treated with pimavanserin achieved adequate symptom control within six months of treatment, compared with 38% of patients receiving low-dose quetiapine. Patients who received pimavanserin for more than six months achieved significantly better symptom control than patients who received any dose of quetiapine.

“Despite the widespread use of quetiapine as a first-line treatment of Parkinson’s disease psychosis, we find that patients treated with 34 mg of pimavanserin achieve significantly better physician-reported control of … symptoms, especially compared with those who receive low-dose quetiapine,” said Dr. Tenenbaum and colleagues. “Increased use of 34 mg of pimavanserin as a first-line pharmacologic treatment for Parkinson’s disease psychosis is suggested to improve outcomes and overall control of symptoms.”

The group of investigators included Doral Fredericks, PharmD, Vice President of Medical Affairs at Acadia Pharmaceuticals in San Diego. Acadia Pharmaceuticals markets Nuplazid, a formulation of pimavanserin.

—Erik Greb

Suggested Reading

Forsaa EB, Larsen JP, Wentzel-Larsen T, et al. A 12-year population-based study of psychosis in Parkinson disease. Arch Neurol. 2010;67(8):996-1001.

MIAMI—Healthy, middle-aged adults may have a fear of falling, but unlike in older adults, this fear does not appear to affect gait and balance, according to a study presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress.

Since ptophobia, the fear of standing or walking, was described in the 1980s, “fear of falling has gained recognition as a health problem of older adults,” said Maria Sheila G. Rocha, MD, PhD, a researcher at Hospital Santa Marcelina in São Paulo, Brazil, and colleagues. In adults older than 65, fear of falling increases the likelihood of falls and injury and limits daily activities. The incidence and impact of fear of falling in younger adults is not known, however.

Dr. Rocha and colleagues aimed to evaluate the prevalence of fear of falling among urban, middle-aged, healthy adults, as well as associated risk factors and fear of falling’s impact on gait and balance in this population.

Their study included 111 healthy participants ages 18 to 95 who lived in São Paulo. The investigators assessed fear of falling using the following four variables from the Brazilian version of the Falls Efficacy Scale-International: history of falls, functional dependency in activities of daily living, cognitive screening test, and activity level. The researchers assessed gait and balance using the Berg Balance Scale, Dynamic Gait Index, Short Physical Performance Battery, and the Performance Oriented Mobility Assessment.

Of the 111 participants, 52.2% were female, mean age was 51.8, and mean Mini-Mental State Examination score was 29.5. Fear of falling was present in 25.2%, and prevalence increased with age. Fear of falling was present in 18.4% of adults younger than 65 and in 48% of those 65 and older.

Fear of walking on an uneven surface and fear of going up or down a slope were the most common fear of falling variables. Being female and older were the main risk factors associated with fear of falling.

Participants with fear of falling performed worse on the Berg Balance Scale and Short Physical Performance Battery than those without. Those younger than 65, however, “had similar gait and balance performance despite the presence of fear of falling,” Dr. Rocha and colleagues said. In addition, physically active participants had less fear of falling.

“Fear of falling creates a psychologic barrier to performing activities for many older adults,” Dr. Rocha and colleagues said. The results suggest that physical activity is a protective factor against fear offalling, the researchers concluded.

MIAMI—Healthy, middle-aged adults may have a fear of falling, but unlike in older adults, this fear does not appear to affect gait and balance, according to a study presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress.

Since ptophobia, the fear of standing or walking, was described in the 1980s, “fear of falling has gained recognition as a health problem of older adults,” said Maria Sheila G. Rocha, MD, PhD, a researcher at Hospital Santa Marcelina in São Paulo, Brazil, and colleagues. In adults older than 65, fear of falling increases the likelihood of falls and injury and limits daily activities. The incidence and impact of fear of falling in younger adults is not known, however.

Dr. Rocha and colleagues aimed to evaluate the prevalence of fear of falling among urban, middle-aged, healthy adults, as well as associated risk factors and fear of falling’s impact on gait and balance in this population.

Their study included 111 healthy participants ages 18 to 95 who lived in São Paulo. The investigators assessed fear of falling using the following four variables from the Brazilian version of the Falls Efficacy Scale-International: history of falls, functional dependency in activities of daily living, cognitive screening test, and activity level. The researchers assessed gait and balance using the Berg Balance Scale, Dynamic Gait Index, Short Physical Performance Battery, and the Performance Oriented Mobility Assessment.

Of the 111 participants, 52.2% were female, mean age was 51.8, and mean Mini-Mental State Examination score was 29.5. Fear of falling was present in 25.2%, and prevalence increased with age. Fear of falling was present in 18.4% of adults younger than 65 and in 48% of those 65 and older.

Fear of walking on an uneven surface and fear of going up or down a slope were the most common fear of falling variables. Being female and older were the main risk factors associated with fear of falling.

Participants with fear of falling performed worse on the Berg Balance Scale and Short Physical Performance Battery than those without. Those younger than 65, however, “had similar gait and balance performance despite the presence of fear of falling,” Dr. Rocha and colleagues said. In addition, physically active participants had less fear of falling.

“Fear of falling creates a psychologic barrier to performing activities for many older adults,” Dr. Rocha and colleagues said. The results suggest that physical activity is a protective factor against fear offalling, the researchers concluded.

MIAMI—Healthy, middle-aged adults may have a fear of falling, but unlike in older adults, this fear does not appear to affect gait and balance, according to a study presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress.

Since ptophobia, the fear of standing or walking, was described in the 1980s, “fear of falling has gained recognition as a health problem of older adults,” said Maria Sheila G. Rocha, MD, PhD, a researcher at Hospital Santa Marcelina in São Paulo, Brazil, and colleagues. In adults older than 65, fear of falling increases the likelihood of falls and injury and limits daily activities. The incidence and impact of fear of falling in younger adults is not known, however.

Dr. Rocha and colleagues aimed to evaluate the prevalence of fear of falling among urban, middle-aged, healthy adults, as well as associated risk factors and fear of falling’s impact on gait and balance in this population.

Their study included 111 healthy participants ages 18 to 95 who lived in São Paulo. The investigators assessed fear of falling using the following four variables from the Brazilian version of the Falls Efficacy Scale-International: history of falls, functional dependency in activities of daily living, cognitive screening test, and activity level. The researchers assessed gait and balance using the Berg Balance Scale, Dynamic Gait Index, Short Physical Performance Battery, and the Performance Oriented Mobility Assessment.

Of the 111 participants, 52.2% were female, mean age was 51.8, and mean Mini-Mental State Examination score was 29.5. Fear of falling was present in 25.2%, and prevalence increased with age. Fear of falling was present in 18.4% of adults younger than 65 and in 48% of those 65 and older.

Fear of walking on an uneven surface and fear of going up or down a slope were the most common fear of falling variables. Being female and older were the main risk factors associated with fear of falling.

Participants with fear of falling performed worse on the Berg Balance Scale and Short Physical Performance Battery than those without. Those younger than 65, however, “had similar gait and balance performance despite the presence of fear of falling,” Dr. Rocha and colleagues said. In addition, physically active participants had less fear of falling.

“Fear of falling creates a psychologic barrier to performing activities for many older adults,” Dr. Rocha and colleagues said. The results suggest that physical activity is a protective factor against fear offalling, the researchers concluded.

MIAMI—For patients with Parkinson’s disease, a regime of transcranial magnetic stimulation (TMS) and aerobic exercise results in motor improvements that are sustained for one month, according to a study presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. Another study by the same researchers indicates that stimulation of two regions in the premotor associative cortex, compared with stimulation of one region, improves axial symptoms in Parkinson’s disease. Both studies suggest that TMS prolongs the cortical silent period.

TMS Prolonged Cortical Silent Period

Aerobic exercise improves the motor symptoms of Parkinson’s disease. A proposed mechanism for this improvement is the enhancement of brain-derived neurotrophic factor (BDNF) signaling or activity. TMS also improves motor symptoms of Parkinson’s disease, and rat studies indicate that it enhances BDNF-tropomyosin receptor kinase B (TrkB) signaling, which is a biomarker of plasticity.

Milton C. Biagioni, MD, Assistant Professor of Neurology at the Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders at NYU Langone Health in New York, and colleagues studied differences in BDNF-TrkB signaling between 16 patients with Parkinson’s disease and five healthy controls. Levels of all TrkB signaling biomarkers were significantly higher in healthy controls than in patients with Parkinson’s disease.

Dr. Biagioni and colleagues also investigated the biologic effects, motor outcomes, and physiologic outcomes of repetitive TMS and aerobic exercise in patients with Parkinson’s disease in a randomized, double-blind trial. In this trial, 16 patients with Parkinson’s disease participated in daily 40-minute sessions of aerobic exercise. Participants were randomized 1:1 to receive high-frequency repetitive TMS or sham stimulation over the motor cortex. Patients exercised on a recumbent linear cross trainer.

Motor outcomes included the Unified Parkinson’s Disease Rating Scale (UPDRS) and Timed Up and Go (TUG) test. Neurophysiologic outcomes included the cortical silent period, motor threshold, and paired-associative stimulation (PAS-25). The researchers obtained peripheral blood lymphocytes from participants in the morning to measure BDNF activity. Outcomes were measured at baseline, two weeks after the intervention, and one month after the intervention.

Among patients with Parkinson’s disease, mean age was about 65. Mean disease duration was eight years, and mean UPDRS III score was 46.4. The researchers found no significant differences at baseline between patients randomized to TMS and those randomized to sham.

BDNF-TrkB signaling increased by 29.3% in the sham group and by 36.6% in the TMS group. Both increases were statistically significant, but the difference between groups was not significant. At one month, the cortical silent period was significantly prolonged after TMS, compared with sham. All patients had significant improvement in UPDRS III. Improvements in UPDRS III and TUG were sustained for one month in the TMS group.

Multifocal Stimulation Improved Axial Score

A previous study indicated that low-frequency repetitive TMS over the supplementary motor area (SMA) effectively improves motor symptoms in Parkinson’s disease. Like the SMA, the dorsal premotor cortex (PMd) is involved in motor planning and motor control. Researchers had not previously studied multifocal TMS over both targets, and Dr. Biagioni and colleagues decided to examine this technique.

They conducted a parallel, active-controlled, double-blind, randomized study of four weekly sessions of low-frequency repetitive TMS in 22 patients with Parkinson’s disease. The control group received TMS over the SMA and sham stimulation over the PMd. The experimental group received TMS over both areas. The study outcomes included all components of the UPDRS, as well as UPDRS III axial, tremor, rigidity, and bradykinesia scores. Dr. Biagioni and colleagues assessed patients in the on state at baseline and at four weeks after treatment.

Participants’ mean age was 65, and eight patients were female. Mean disease duration was approximately nine years, mean UPDRS total score was 53.1, and mean UPDRS III score was 35.9. The only significant difference between the control and experimental groups at baseline was Montreal Cognitive Assessment score, which was 24.2 in the control group and 26.4 in the experimental group.

Both interventions were well tolerated. After one month, UPDRS III decreased by 5.5 points in the control group and by 6.5 points in the experimental group. Both changes were statistically significant, but the difference between groups was not significant. The researchers found no difference between groups in total UPDRS and UPDRS III after one month. Axial score significantly decreased in the experimental group, compared with the control group, but the researchers found no significant differences between groups in rigidity, tremor, or bradykinesia scores. In addition, the cortical silent period was significantly prolonged in the experimental group, compared with the control group.

—Erik Greb

Suggested Reading

Chou YH, Hickey PT, Sundman M, et al. Effects of repetitive transcranial magnetic stimulation on motor symptoms in Parkinson disease: a systematic review and meta-analysis. JAMA Neurol. 2015;72(4):432-440.

Shirota Y, Ohtsu H, Hamada M, et al. Supplementary motor area stimulation for Parkinson disease: a randomized controlled study. Neurology. 2013;80(15):1400-1405.

MIAMI—For patients with Parkinson’s disease, a regime of transcranial magnetic stimulation (TMS) and aerobic exercise results in motor improvements that are sustained for one month, according to a study presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. Another study by the same researchers indicates that stimulation of two regions in the premotor associative cortex, compared with stimulation of one region, improves axial symptoms in Parkinson’s disease. Both studies suggest that TMS prolongs the cortical silent period.

TMS Prolonged Cortical Silent Period

Aerobic exercise improves the motor symptoms of Parkinson’s disease. A proposed mechanism for this improvement is the enhancement of brain-derived neurotrophic factor (BDNF) signaling or activity. TMS also improves motor symptoms of Parkinson’s disease, and rat studies indicate that it enhances BDNF-tropomyosin receptor kinase B (TrkB) signaling, which is a biomarker of plasticity.

Milton C. Biagioni, MD, Assistant Professor of Neurology at the Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders at NYU Langone Health in New York, and colleagues studied differences in BDNF-TrkB signaling between 16 patients with Parkinson’s disease and five healthy controls. Levels of all TrkB signaling biomarkers were significantly higher in healthy controls than in patients with Parkinson’s disease.

Dr. Biagioni and colleagues also investigated the biologic effects, motor outcomes, and physiologic outcomes of repetitive TMS and aerobic exercise in patients with Parkinson’s disease in a randomized, double-blind trial. In this trial, 16 patients with Parkinson’s disease participated in daily 40-minute sessions of aerobic exercise. Participants were randomized 1:1 to receive high-frequency repetitive TMS or sham stimulation over the motor cortex. Patients exercised on a recumbent linear cross trainer.

Motor outcomes included the Unified Parkinson’s Disease Rating Scale (UPDRS) and Timed Up and Go (TUG) test. Neurophysiologic outcomes included the cortical silent period, motor threshold, and paired-associative stimulation (PAS-25). The researchers obtained peripheral blood lymphocytes from participants in the morning to measure BDNF activity. Outcomes were measured at baseline, two weeks after the intervention, and one month after the intervention.

Among patients with Parkinson’s disease, mean age was about 65. Mean disease duration was eight years, and mean UPDRS III score was 46.4. The researchers found no significant differences at baseline between patients randomized to TMS and those randomized to sham.

BDNF-TrkB signaling increased by 29.3% in the sham group and by 36.6% in the TMS group. Both increases were statistically significant, but the difference between groups was not significant. At one month, the cortical silent period was significantly prolonged after TMS, compared with sham. All patients had significant improvement in UPDRS III. Improvements in UPDRS III and TUG were sustained for one month in the TMS group.

Multifocal Stimulation Improved Axial Score

A previous study indicated that low-frequency repetitive TMS over the supplementary motor area (SMA) effectively improves motor symptoms in Parkinson’s disease. Like the SMA, the dorsal premotor cortex (PMd) is involved in motor planning and motor control. Researchers had not previously studied multifocal TMS over both targets, and Dr. Biagioni and colleagues decided to examine this technique.

They conducted a parallel, active-controlled, double-blind, randomized study of four weekly sessions of low-frequency repetitive TMS in 22 patients with Parkinson’s disease. The control group received TMS over the SMA and sham stimulation over the PMd. The experimental group received TMS over both areas. The study outcomes included all components of the UPDRS, as well as UPDRS III axial, tremor, rigidity, and bradykinesia scores. Dr. Biagioni and colleagues assessed patients in the on state at baseline and at four weeks after treatment.

Participants’ mean age was 65, and eight patients were female. Mean disease duration was approximately nine years, mean UPDRS total score was 53.1, and mean UPDRS III score was 35.9. The only significant difference between the control and experimental groups at baseline was Montreal Cognitive Assessment score, which was 24.2 in the control group and 26.4 in the experimental group.

Both interventions were well tolerated. After one month, UPDRS III decreased by 5.5 points in the control group and by 6.5 points in the experimental group. Both changes were statistically significant, but the difference between groups was not significant. The researchers found no difference between groups in total UPDRS and UPDRS III after one month. Axial score significantly decreased in the experimental group, compared with the control group, but the researchers found no significant differences between groups in rigidity, tremor, or bradykinesia scores. In addition, the cortical silent period was significantly prolonged in the experimental group, compared with the control group.

—Erik Greb

Suggested Reading

Chou YH, Hickey PT, Sundman M, et al. Effects of repetitive transcranial magnetic stimulation on motor symptoms in Parkinson disease: a systematic review and meta-analysis. JAMA Neurol. 2015;72(4):432-440.

Shirota Y, Ohtsu H, Hamada M, et al. Supplementary motor area stimulation for Parkinson disease: a randomized controlled study. Neurology. 2013;80(15):1400-1405.

MIAMI—For patients with Parkinson’s disease, a regime of transcranial magnetic stimulation (TMS) and aerobic exercise results in motor improvements that are sustained for one month, according to a study presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. Another study by the same researchers indicates that stimulation of two regions in the premotor associative cortex, compared with stimulation of one region, improves axial symptoms in Parkinson’s disease. Both studies suggest that TMS prolongs the cortical silent period.

TMS Prolonged Cortical Silent Period

Aerobic exercise improves the motor symptoms of Parkinson’s disease. A proposed mechanism for this improvement is the enhancement of brain-derived neurotrophic factor (BDNF) signaling or activity. TMS also improves motor symptoms of Parkinson’s disease, and rat studies indicate that it enhances BDNF-tropomyosin receptor kinase B (TrkB) signaling, which is a biomarker of plasticity.

Milton C. Biagioni, MD, Assistant Professor of Neurology at the Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders at NYU Langone Health in New York, and colleagues studied differences in BDNF-TrkB signaling between 16 patients with Parkinson’s disease and five healthy controls. Levels of all TrkB signaling biomarkers were significantly higher in healthy controls than in patients with Parkinson’s disease.

Dr. Biagioni and colleagues also investigated the biologic effects, motor outcomes, and physiologic outcomes of repetitive TMS and aerobic exercise in patients with Parkinson’s disease in a randomized, double-blind trial. In this trial, 16 patients with Parkinson’s disease participated in daily 40-minute sessions of aerobic exercise. Participants were randomized 1:1 to receive high-frequency repetitive TMS or sham stimulation over the motor cortex. Patients exercised on a recumbent linear cross trainer.

Motor outcomes included the Unified Parkinson’s Disease Rating Scale (UPDRS) and Timed Up and Go (TUG) test. Neurophysiologic outcomes included the cortical silent period, motor threshold, and paired-associative stimulation (PAS-25). The researchers obtained peripheral blood lymphocytes from participants in the morning to measure BDNF activity. Outcomes were measured at baseline, two weeks after the intervention, and one month after the intervention.

Among patients with Parkinson’s disease, mean age was about 65. Mean disease duration was eight years, and mean UPDRS III score was 46.4. The researchers found no significant differences at baseline between patients randomized to TMS and those randomized to sham.

BDNF-TrkB signaling increased by 29.3% in the sham group and by 36.6% in the TMS group. Both increases were statistically significant, but the difference between groups was not significant. At one month, the cortical silent period was significantly prolonged after TMS, compared with sham. All patients had significant improvement in UPDRS III. Improvements in UPDRS III and TUG were sustained for one month in the TMS group.

Multifocal Stimulation Improved Axial Score

A previous study indicated that low-frequency repetitive TMS over the supplementary motor area (SMA) effectively improves motor symptoms in Parkinson’s disease. Like the SMA, the dorsal premotor cortex (PMd) is involved in motor planning and motor control. Researchers had not previously studied multifocal TMS over both targets, and Dr. Biagioni and colleagues decided to examine this technique.

They conducted a parallel, active-controlled, double-blind, randomized study of four weekly sessions of low-frequency repetitive TMS in 22 patients with Parkinson’s disease. The control group received TMS over the SMA and sham stimulation over the PMd. The experimental group received TMS over both areas. The study outcomes included all components of the UPDRS, as well as UPDRS III axial, tremor, rigidity, and bradykinesia scores. Dr. Biagioni and colleagues assessed patients in the on state at baseline and at four weeks after treatment.

Participants’ mean age was 65, and eight patients were female. Mean disease duration was approximately nine years, mean UPDRS total score was 53.1, and mean UPDRS III score was 35.9. The only significant difference between the control and experimental groups at baseline was Montreal Cognitive Assessment score, which was 24.2 in the control group and 26.4 in the experimental group.

Both interventions were well tolerated. After one month, UPDRS III decreased by 5.5 points in the control group and by 6.5 points in the experimental group. Both changes were statistically significant, but the difference between groups was not significant. The researchers found no difference between groups in total UPDRS and UPDRS III after one month. Axial score significantly decreased in the experimental group, compared with the control group, but the researchers found no significant differences between groups in rigidity, tremor, or bradykinesia scores. In addition, the cortical silent period was significantly prolonged in the experimental group, compared with the control group.

—Erik Greb

Suggested Reading

Chou YH, Hickey PT, Sundman M, et al. Effects of repetitive transcranial magnetic stimulation on motor symptoms in Parkinson disease: a systematic review and meta-analysis. JAMA Neurol. 2015;72(4):432-440.

Shirota Y, Ohtsu H, Hamada M, et al. Supplementary motor area stimulation for Parkinson disease: a randomized controlled study. Neurology. 2013;80(15):1400-1405.

MIAMI—Anxiety and depressive disorders may precede Parkinson’s disease diagnosis in more than half of patients—anxiety by 25 years and depression by 17 years, on average, according to research described at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. The data suggest that “neurodegenerative changes may be present in the limbic system before affecting motor circuits,” said the researchers.

“Anxiety, depression, impulse control disorders, irritability, mania, psychosis, and cognitive deficits are the most common psychiatric features of Parkinson’s disease,” said Andreea L. Seritan, MD, Professor of Psychiatry at the University of California, San Francisco (UCSF), and colleagues. Previous research has indicated that anxiety and depression increase the risk of Parkinson’s disease.

A Retrospective Chart Review

To examine the lifetime prevalence of psychiatric disorders and compare the onset ages of anxiety and depressive disorders with ages at Parkinson’s disease diagnosis, Dr. Seritan and colleagues conducted a retrospective chart review of patients with Parkinson’s disease who were evaluated by psychiatrists at the UCSF Movement Disorders and Neuromodulation Center. The center provides comprehensive, multidisciplinary evaluation and management of patients with movement disorders.

The researchers analyzed data from all 108 patients with Parkinson’s disease seen between October 2015 and January 2018.

Psychiatric diagnoses and onset ages were established through clinical interview, using DSM-V criteria. Researchers used neurologists’ notes to identify age of Parkinson’s disease diagnosis. When exact onset ages were not available, the researchers imputed missing onset ages by decade of life.

Most Patients Had a Lifetime Prevalence of Depressive Disorders

Of the 108 participants, 33.3% were women, and the mean age was 63.7. In all, 67% of patients had a lifetime prevalence of anxiety disorders, and 87% of participants had a lifetime prevalence of depressive disorders.

Psychiatric symptoms preceded Parkinson’s disease diagnosis in 48 (72%) patients with anxiety disorders and in 58 (68%) of those with depressive disorders. “Both anxiety and depressive disorders had onset in the fourth decade of life, on average, preceding Parkinson’s disease diagnosis by approximately two decades,” Dr. Seritan and colleagues said.

—Erica Tricarico

MIAMI—Anxiety and depressive disorders may precede Parkinson’s disease diagnosis in more than half of patients—anxiety by 25 years and depression by 17 years, on average, according to research described at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. The data suggest that “neurodegenerative changes may be present in the limbic system before affecting motor circuits,” said the researchers.

“Anxiety, depression, impulse control disorders, irritability, mania, psychosis, and cognitive deficits are the most common psychiatric features of Parkinson’s disease,” said Andreea L. Seritan, MD, Professor of Psychiatry at the University of California, San Francisco (UCSF), and colleagues. Previous research has indicated that anxiety and depression increase the risk of Parkinson’s disease.

A Retrospective Chart Review

To examine the lifetime prevalence of psychiatric disorders and compare the onset ages of anxiety and depressive disorders with ages at Parkinson’s disease diagnosis, Dr. Seritan and colleagues conducted a retrospective chart review of patients with Parkinson’s disease who were evaluated by psychiatrists at the UCSF Movement Disorders and Neuromodulation Center. The center provides comprehensive, multidisciplinary evaluation and management of patients with movement disorders.

The researchers analyzed data from all 108 patients with Parkinson’s disease seen between October 2015 and January 2018.

Psychiatric diagnoses and onset ages were established through clinical interview, using DSM-V criteria. Researchers used neurologists’ notes to identify age of Parkinson’s disease diagnosis. When exact onset ages were not available, the researchers imputed missing onset ages by decade of life.

Most Patients Had a Lifetime Prevalence of Depressive Disorders

Of the 108 participants, 33.3% were women, and the mean age was 63.7. In all, 67% of patients had a lifetime prevalence of anxiety disorders, and 87% of participants had a lifetime prevalence of depressive disorders.

Psychiatric symptoms preceded Parkinson’s disease diagnosis in 48 (72%) patients with anxiety disorders and in 58 (68%) of those with depressive disorders. “Both anxiety and depressive disorders had onset in the fourth decade of life, on average, preceding Parkinson’s disease diagnosis by approximately two decades,” Dr. Seritan and colleagues said.

—Erica Tricarico

MIAMI—Anxiety and depressive disorders may precede Parkinson’s disease diagnosis in more than half of patients—anxiety by 25 years and depression by 17 years, on average, according to research described at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. The data suggest that “neurodegenerative changes may be present in the limbic system before affecting motor circuits,” said the researchers.

“Anxiety, depression, impulse control disorders, irritability, mania, psychosis, and cognitive deficits are the most common psychiatric features of Parkinson’s disease,” said Andreea L. Seritan, MD, Professor of Psychiatry at the University of California, San Francisco (UCSF), and colleagues. Previous research has indicated that anxiety and depression increase the risk of Parkinson’s disease.

A Retrospective Chart Review

To examine the lifetime prevalence of psychiatric disorders and compare the onset ages of anxiety and depressive disorders with ages at Parkinson’s disease diagnosis, Dr. Seritan and colleagues conducted a retrospective chart review of patients with Parkinson’s disease who were evaluated by psychiatrists at the UCSF Movement Disorders and Neuromodulation Center. The center provides comprehensive, multidisciplinary evaluation and management of patients with movement disorders.

The researchers analyzed data from all 108 patients with Parkinson’s disease seen between October 2015 and January 2018.

Psychiatric diagnoses and onset ages were established through clinical interview, using DSM-V criteria. Researchers used neurologists’ notes to identify age of Parkinson’s disease diagnosis. When exact onset ages were not available, the researchers imputed missing onset ages by decade of life.

Most Patients Had a Lifetime Prevalence of Depressive Disorders

Of the 108 participants, 33.3% were women, and the mean age was 63.7. In all, 67% of patients had a lifetime prevalence of anxiety disorders, and 87% of participants had a lifetime prevalence of depressive disorders.

Psychiatric symptoms preceded Parkinson’s disease diagnosis in 48 (72%) patients with anxiety disorders and in 58 (68%) of those with depressive disorders. “Both anxiety and depressive disorders had onset in the fourth decade of life, on average, preceding Parkinson’s disease diagnosis by approximately two decades,” Dr. Seritan and colleagues said.

—Erica Tricarico

Thrombectomy Is Feasible for the Elderly, but Entails Risks

Mechanical thrombectomy is an increasingly important therapy for acute stroke that can benefit the very old, assuming a careful selection of patients and risk assessment, according to a Portuguese study.

For several years, endovascular thrombectomy has been a way of removing larger vascular obstructions. In this procedure, the thrombus is extracted from the cerebral vessel via a catheter inserted in the groin. Numerous international studies have shown that endovascular treatment is a substantial improvement over purely drug-based therapy. The procedure is especially effective in dealing with extremely long blood clots and large obstructions of the cerebral arteries and often yields positive results. Thanks to this procedure, more than 60% of patients treated survive the stroke with no or minor subsequent impairment.

“More and more study results show the high effectiveness of mechanical removal of blood clots after a stroke. But researchers are still trying to determine the type of patient for whom this relatively new procedure is the best treatment option,” said Ary Lopes de Sousa, MD, a neurology resident at Central Lisbon Hospital Center.

Dr. de Sousa and his colleagues reviewed the treatment success of thrombectomy in more than 200 patients with anterior acute ischemic stroke and no or slight disability prior to this event. The researchers separated patients into two groups: one with individuals younger than 80 and one with individuals age 80 and older.

In the group of patients age 80 and older, hypertension and transient ischemic attacks were more frequent. The treatment did not differ between the two groups (eg, in terms of the time frame of the revascularization). But in the older group, two-thirds of the patients exhibited a poor functional outcome at three months after the treatment (ie, they were moderately or severely limited in their ability to handle their daily tasks). The number of impaired individuals in that group was substantially larger than in the younger group, where 46% faced limitations in their everyday lives. On the other hand, one-third of the patients age 80 and older were able to handle their everyday lives three months after the treatment with no or mild impairments from the stroke. No difference in mortality was observed between the two age groups.

“For patients over 80, thrombectomy appears to be riskier than for younger patients,” said Dr. de Sousa. “But one third of the patients over 80 can be fully functional in their everyday lives after the procedure, so we must identify the factors associated with this favorable outcome. This [step] will support us applying this modern procedure efficiently to those individuals among the very old who can benefit from it.”

Studies Gauge the Cost of Migraine

A pair of studies have evaluated the cost of migraine to individuals, society, and businesses. A French study looked at the socioeconomic impact of the condition. In a survey of more than 7,700 people, a representative sample of the general population, 3.8% indicated that they experienced severe migraines on at least eight days per month. “Two-thirds of those [patients] were women, and the average age of those affected was 41, meaning that migraines significantly affect people at the peak of their careers, and who have families to provide for. These regular attacks represent a serious problem as far as keeping their jobs is concerned,” said Dr. Guillaume Leiba, Pricing and Market Access Manager at Novartis in Paris. In the current study, patients with severe migraine reported missing 33 working days per year because of their condition. This absence translates into a cost to society of approximately EUR 3.8 billion. Migraine also has an impact on patients’ social environment: 14% of respondents indicated that family members had to adjust their working hours because of patients’ migraine headaches. The study also quantified the financial burden placed on migraineurs: 58% reported an average monthly cost of more than EUR 30 per month for nonreimbursed medicines. Approximately 43% spent more than EUR 50 each month on other, nonpharmaceutical therapies. Despite the high level of public and private spending associated with the condition, quality of life for migraineurs remains far from satisfactory. More than three-quarters have sleep disorders and benefit less from their free time than healthy controls.

A Swiss study obtained more detailed results regarding absenteeism in the workplace. A group of 700 working migraineurs reported losing an average of 32 days per year because of migraine. This rate is similar to that reported in the French study. But there were significant differences depending on the specific type of headache, according to study author François Cadiou, CEO of Healint in Singapore. “With an average of more than 56 working days missed per year, patients with chronic migraine had the highest rate of absenteeism. People with episodic migraine were unable to go to work on 33 days of the year, while those with low-frequency episodic migraine took an average of 15 days off because of their condition.” Another finding has implications for preventive measures: the number of sick days was not always constant. In fact, the total steadily increased, and with it the amount of medication taken if patients indicated anxiety or depression as a symptom or trigger at least once within the 28-day observation period. In light of the outcomes presented, experts at the EAN Congress have issued a call for increased investment in migraine research and prevention, citing the advantages to society.

Both studies were funded by Novartis Pharma.

Parkinson’s Disease Progression Varies by Gender

A current study has now furnished the first neurophysiologic evidence that Parkinson’s disease progresses differently in women than in men. “Numerous demographic studies have provided evidence that men contract Parkinson’s disease nearly twice as often as women. What was unclear, however, was whether a gender-specific pathophysiology exists as soon as the first symptoms appear,” said Maja Kojovic, MD, PhD, a consultant neurologist at Ljubljana University Medical Center in Slovenia.

The international research team proceeded from the concept that in early Parkinson’s disease, functional changes can be detected in the primary motor cortex (M1) using transcranial magnetic stimulation (TMS). If pathophysiology differs between genders in Parkinson’s disease, they hypothesized, it will be reflected in differences of M1 TMS measurements.

Thirty-nine newly diagnosed and untreated patients with Parkinson’s disease (23 males) were assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS). Then the patients and a group of healthy controls underwent TMS measurements of motor thresholds of the brain, input–output curve, short interval intracortical inhibition, cortical silent period, and intracortical facilitation. Brain plasticity was also measured using paired associative stimulation.

The UPDRS tests did not yield any differences in motor scores between the genders. However, the female patients had a less steep input–output curve than the male patients on the side of the brain more affected by Parkinson’s disease.

The women with Parkinson’s disease also exhibited better preserved short interval intracortical inhibition in both hemispheres, compared with affected men, and tended to have a better response to the paired associative stimulation protocol on the side less affected by symptoms. No gender-specific differences were determined, however, in the motor thresholds, intracortical facilitation, and the cortical silent period. The healthy control group did not show any gender or interhemispheric differences for any of the TMS parameters measured. “The detected gender differences in corticospinal and intracortical excitability in patients with early untreated Parkinson’s disease represent differences in disease pathophysiology. Gender may also prove to be a relevant factor when choosing appropriate treatment,” said Dr. Kojovic.

EAN Develops Guideline on Palliative Care of Patients With Severe MS

A cohort of 934 individuals affected by multiple sclerosis (MS) from seven European countries played an instrumental part in developing the European Academy of Neurology’s (EAN) new guideline on palliative care for people with severe MS. “There were 751 MS patients and 183 caregiver relatives involved,” said Sascha Köpke, PhD, Professor of Nursing Research at the University of Lübeck in Germany.

With the involvement of patients and their families in a new guideline, the EAN is emphasizing shared decision-making as an increasingly important concept that underscores patient autonomy and promotes the individualization of diagnosis and therapy. According to this approach, patients and physicians undergo a detailed consultation and then choose the medical treatment. The EAN has supported this patient-centered approach for a long time, and it is becoming increasingly established in other medical areas as well.

“It was resource- and time-intensive to include consumers in the guideline process, but also highly rewarding,” said Prof. Köpke. “Patients and caregivers really helped us to formulate the guideline in a way that was in line with actual practice and their own needs. We were able to see clearly which of our ideas met with approval or rejection.” The comments were also instructive for the group of EAN experts. They raised new aspects as well as sensitive issues that had been left out of the first draft.

Two approaches were chosen to ensure that consumers would participate. “First, there was an international online survey launched by national MS societies following a trial run involving 20 patients and 18 caregivers. Second, we invited MS patients and caregiver relatives to focus group meetings,” said Prof. Köpke. The majority of participants approved the topics proposed by the EAN group of experts. About 98% agreed to incorporate the subject of multidisciplinary rehabilitation in the guideline. There were 569 free comments, of which 182 (32%) pertained to the specified topics. A further 227 comments (40%) addressed additional topics, of which 16 were pertinent to the guideline. Five of the focus group meetings corroborated the results of the online survey and helped to work out important issues for the individuals affected. “The involvement of patients and caregivers increases the reliability and relevance of the guideline for clinical practice,” said Prof. Köpke.

Thrombectomy Is Feasible for the Elderly, but Entails Risks

Mechanical thrombectomy is an increasingly important therapy for acute stroke that can benefit the very old, assuming a careful selection of patients and risk assessment, according to a Portuguese study.

For several years, endovascular thrombectomy has been a way of removing larger vascular obstructions. In this procedure, the thrombus is extracted from the cerebral vessel via a catheter inserted in the groin. Numerous international studies have shown that endovascular treatment is a substantial improvement over purely drug-based therapy. The procedure is especially effective in dealing with extremely long blood clots and large obstructions of the cerebral arteries and often yields positive results. Thanks to this procedure, more than 60% of patients treated survive the stroke with no or minor subsequent impairment.

“More and more study results show the high effectiveness of mechanical removal of blood clots after a stroke. But researchers are still trying to determine the type of patient for whom this relatively new procedure is the best treatment option,” said Ary Lopes de Sousa, MD, a neurology resident at Central Lisbon Hospital Center.

Dr. de Sousa and his colleagues reviewed the treatment success of thrombectomy in more than 200 patients with anterior acute ischemic stroke and no or slight disability prior to this event. The researchers separated patients into two groups: one with individuals younger than 80 and one with individuals age 80 and older.

In the group of patients age 80 and older, hypertension and transient ischemic attacks were more frequent. The treatment did not differ between the two groups (eg, in terms of the time frame of the revascularization). But in the older group, two-thirds of the patients exhibited a poor functional outcome at three months after the treatment (ie, they were moderately or severely limited in their ability to handle their daily tasks). The number of impaired individuals in that group was substantially larger than in the younger group, where 46% faced limitations in their everyday lives. On the other hand, one-third of the patients age 80 and older were able to handle their everyday lives three months after the treatment with no or mild impairments from the stroke. No difference in mortality was observed between the two age groups.

“For patients over 80, thrombectomy appears to be riskier than for younger patients,” said Dr. de Sousa. “But one third of the patients over 80 can be fully functional in their everyday lives after the procedure, so we must identify the factors associated with this favorable outcome. This [step] will support us applying this modern procedure efficiently to those individuals among the very old who can benefit from it.”

Studies Gauge the Cost of Migraine

A pair of studies have evaluated the cost of migraine to individuals, society, and businesses. A French study looked at the socioeconomic impact of the condition. In a survey of more than 7,700 people, a representative sample of the general population, 3.8% indicated that they experienced severe migraines on at least eight days per month. “Two-thirds of those [patients] were women, and the average age of those affected was 41, meaning that migraines significantly affect people at the peak of their careers, and who have families to provide for. These regular attacks represent a serious problem as far as keeping their jobs is concerned,” said Dr. Guillaume Leiba, Pricing and Market Access Manager at Novartis in Paris. In the current study, patients with severe migraine reported missing 33 working days per year because of their condition. This absence translates into a cost to society of approximately EUR 3.8 billion. Migraine also has an impact on patients’ social environment: 14% of respondents indicated that family members had to adjust their working hours because of patients’ migraine headaches. The study also quantified the financial burden placed on migraineurs: 58% reported an average monthly cost of more than EUR 30 per month for nonreimbursed medicines. Approximately 43% spent more than EUR 50 each month on other, nonpharmaceutical therapies. Despite the high level of public and private spending associated with the condition, quality of life for migraineurs remains far from satisfactory. More than three-quarters have sleep disorders and benefit less from their free time than healthy controls.

A Swiss study obtained more detailed results regarding absenteeism in the workplace. A group of 700 working migraineurs reported losing an average of 32 days per year because of migraine. This rate is similar to that reported in the French study. But there were significant differences depending on the specific type of headache, according to study author François Cadiou, CEO of Healint in Singapore. “With an average of more than 56 working days missed per year, patients with chronic migraine had the highest rate of absenteeism. People with episodic migraine were unable to go to work on 33 days of the year, while those with low-frequency episodic migraine took an average of 15 days off because of their condition.” Another finding has implications for preventive measures: the number of sick days was not always constant. In fact, the total steadily increased, and with it the amount of medication taken if patients indicated anxiety or depression as a symptom or trigger at least once within the 28-day observation period. In light of the outcomes presented, experts at the EAN Congress have issued a call for increased investment in migraine research and prevention, citing the advantages to society.

Both studies were funded by Novartis Pharma.

Parkinson’s Disease Progression Varies by Gender

A current study has now furnished the first neurophysiologic evidence that Parkinson’s disease progresses differently in women than in men. “Numerous demographic studies have provided evidence that men contract Parkinson’s disease nearly twice as often as women. What was unclear, however, was whether a gender-specific pathophysiology exists as soon as the first symptoms appear,” said Maja Kojovic, MD, PhD, a consultant neurologist at Ljubljana University Medical Center in Slovenia.

The international research team proceeded from the concept that in early Parkinson’s disease, functional changes can be detected in the primary motor cortex (M1) using transcranial magnetic stimulation (TMS). If pathophysiology differs between genders in Parkinson’s disease, they hypothesized, it will be reflected in differences of M1 TMS measurements.

Thirty-nine newly diagnosed and untreated patients with Parkinson’s disease (23 males) were assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS). Then the patients and a group of healthy controls underwent TMS measurements of motor thresholds of the brain, input–output curve, short interval intracortical inhibition, cortical silent period, and intracortical facilitation. Brain plasticity was also measured using paired associative stimulation.

The UPDRS tests did not yield any differences in motor scores between the genders. However, the female patients had a less steep input–output curve than the male patients on the side of the brain more affected by Parkinson’s disease.

The women with Parkinson’s disease also exhibited better preserved short interval intracortical inhibition in both hemispheres, compared with affected men, and tended to have a better response to the paired associative stimulation protocol on the side less affected by symptoms. No gender-specific differences were determined, however, in the motor thresholds, intracortical facilitation, and the cortical silent period. The healthy control group did not show any gender or interhemispheric differences for any of the TMS parameters measured. “The detected gender differences in corticospinal and intracortical excitability in patients with early untreated Parkinson’s disease represent differences in disease pathophysiology. Gender may also prove to be a relevant factor when choosing appropriate treatment,” said Dr. Kojovic.

EAN Develops Guideline on Palliative Care of Patients With Severe MS

A cohort of 934 individuals affected by multiple sclerosis (MS) from seven European countries played an instrumental part in developing the European Academy of Neurology’s (EAN) new guideline on palliative care for people with severe MS. “There were 751 MS patients and 183 caregiver relatives involved,” said Sascha Köpke, PhD, Professor of Nursing Research at the University of Lübeck in Germany.

With the involvement of patients and their families in a new guideline, the EAN is emphasizing shared decision-making as an increasingly important concept that underscores patient autonomy and promotes the individualization of diagnosis and therapy. According to this approach, patients and physicians undergo a detailed consultation and then choose the medical treatment. The EAN has supported this patient-centered approach for a long time, and it is becoming increasingly established in other medical areas as well.

“It was resource- and time-intensive to include consumers in the guideline process, but also highly rewarding,” said Prof. Köpke. “Patients and caregivers really helped us to formulate the guideline in a way that was in line with actual practice and their own needs. We were able to see clearly which of our ideas met with approval or rejection.” The comments were also instructive for the group of EAN experts. They raised new aspects as well as sensitive issues that had been left out of the first draft.

Two approaches were chosen to ensure that consumers would participate. “First, there was an international online survey launched by national MS societies following a trial run involving 20 patients and 18 caregivers. Second, we invited MS patients and caregiver relatives to focus group meetings,” said Prof. Köpke. The majority of participants approved the topics proposed by the EAN group of experts. About 98% agreed to incorporate the subject of multidisciplinary rehabilitation in the guideline. There were 569 free comments, of which 182 (32%) pertained to the specified topics. A further 227 comments (40%) addressed additional topics, of which 16 were pertinent to the guideline. Five of the focus group meetings corroborated the results of the online survey and helped to work out important issues for the individuals affected. “The involvement of patients and caregivers increases the reliability and relevance of the guideline for clinical practice,” said Prof. Köpke.

Thrombectomy Is Feasible for the Elderly, but Entails Risks

Mechanical thrombectomy is an increasingly important therapy for acute stroke that can benefit the very old, assuming a careful selection of patients and risk assessment, according to a Portuguese study.

For several years, endovascular thrombectomy has been a way of removing larger vascular obstructions. In this procedure, the thrombus is extracted from the cerebral vessel via a catheter inserted in the groin. Numerous international studies have shown that endovascular treatment is a substantial improvement over purely drug-based therapy. The procedure is especially effective in dealing with extremely long blood clots and large obstructions of the cerebral arteries and often yields positive results. Thanks to this procedure, more than 60% of patients treated survive the stroke with no or minor subsequent impairment.

“More and more study results show the high effectiveness of mechanical removal of blood clots after a stroke. But researchers are still trying to determine the type of patient for whom this relatively new procedure is the best treatment option,” said Ary Lopes de Sousa, MD, a neurology resident at Central Lisbon Hospital Center.

Dr. de Sousa and his colleagues reviewed the treatment success of thrombectomy in more than 200 patients with anterior acute ischemic stroke and no or slight disability prior to this event. The researchers separated patients into two groups: one with individuals younger than 80 and one with individuals age 80 and older.

In the group of patients age 80 and older, hypertension and transient ischemic attacks were more frequent. The treatment did not differ between the two groups (eg, in terms of the time frame of the revascularization). But in the older group, two-thirds of the patients exhibited a poor functional outcome at three months after the treatment (ie, they were moderately or severely limited in their ability to handle their daily tasks). The number of impaired individuals in that group was substantially larger than in the younger group, where 46% faced limitations in their everyday lives. On the other hand, one-third of the patients age 80 and older were able to handle their everyday lives three months after the treatment with no or mild impairments from the stroke. No difference in mortality was observed between the two age groups.

“For patients over 80, thrombectomy appears to be riskier than for younger patients,” said Dr. de Sousa. “But one third of the patients over 80 can be fully functional in their everyday lives after the procedure, so we must identify the factors associated with this favorable outcome. This [step] will support us applying this modern procedure efficiently to those individuals among the very old who can benefit from it.”

Studies Gauge the Cost of Migraine

A pair of studies have evaluated the cost of migraine to individuals, society, and businesses. A French study looked at the socioeconomic impact of the condition. In a survey of more than 7,700 people, a representative sample of the general population, 3.8% indicated that they experienced severe migraines on at least eight days per month. “Two-thirds of those [patients] were women, and the average age of those affected was 41, meaning that migraines significantly affect people at the peak of their careers, and who have families to provide for. These regular attacks represent a serious problem as far as keeping their jobs is concerned,” said Dr. Guillaume Leiba, Pricing and Market Access Manager at Novartis in Paris. In the current study, patients with severe migraine reported missing 33 working days per year because of their condition. This absence translates into a cost to society of approximately EUR 3.8 billion. Migraine also has an impact on patients’ social environment: 14% of respondents indicated that family members had to adjust their working hours because of patients’ migraine headaches. The study also quantified the financial burden placed on migraineurs: 58% reported an average monthly cost of more than EUR 30 per month for nonreimbursed medicines. Approximately 43% spent more than EUR 50 each month on other, nonpharmaceutical therapies. Despite the high level of public and private spending associated with the condition, quality of life for migraineurs remains far from satisfactory. More than three-quarters have sleep disorders and benefit less from their free time than healthy controls.

A Swiss study obtained more detailed results regarding absenteeism in the workplace. A group of 700 working migraineurs reported losing an average of 32 days per year because of migraine. This rate is similar to that reported in the French study. But there were significant differences depending on the specific type of headache, according to study author François Cadiou, CEO of Healint in Singapore. “With an average of more than 56 working days missed per year, patients with chronic migraine had the highest rate of absenteeism. People with episodic migraine were unable to go to work on 33 days of the year, while those with low-frequency episodic migraine took an average of 15 days off because of their condition.” Another finding has implications for preventive measures: the number of sick days was not always constant. In fact, the total steadily increased, and with it the amount of medication taken if patients indicated anxiety or depression as a symptom or trigger at least once within the 28-day observation period. In light of the outcomes presented, experts at the EAN Congress have issued a call for increased investment in migraine research and prevention, citing the advantages to society.

Both studies were funded by Novartis Pharma.

Parkinson’s Disease Progression Varies by Gender

A current study has now furnished the first neurophysiologic evidence that Parkinson’s disease progresses differently in women than in men. “Numerous demographic studies have provided evidence that men contract Parkinson’s disease nearly twice as often as women. What was unclear, however, was whether a gender-specific pathophysiology exists as soon as the first symptoms appear,” said Maja Kojovic, MD, PhD, a consultant neurologist at Ljubljana University Medical Center in Slovenia.

The international research team proceeded from the concept that in early Parkinson’s disease, functional changes can be detected in the primary motor cortex (M1) using transcranial magnetic stimulation (TMS). If pathophysiology differs between genders in Parkinson’s disease, they hypothesized, it will be reflected in differences of M1 TMS measurements.

Thirty-nine newly diagnosed and untreated patients with Parkinson’s disease (23 males) were assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS). Then the patients and a group of healthy controls underwent TMS measurements of motor thresholds of the brain, input–output curve, short interval intracortical inhibition, cortical silent period, and intracortical facilitation. Brain plasticity was also measured using paired associative stimulation.

The UPDRS tests did not yield any differences in motor scores between the genders. However, the female patients had a less steep input–output curve than the male patients on the side of the brain more affected by Parkinson’s disease.

The women with Parkinson’s disease also exhibited better preserved short interval intracortical inhibition in both hemispheres, compared with affected men, and tended to have a better response to the paired associative stimulation protocol on the side less affected by symptoms. No gender-specific differences were determined, however, in the motor thresholds, intracortical facilitation, and the cortical silent period. The healthy control group did not show any gender or interhemispheric differences for any of the TMS parameters measured. “The detected gender differences in corticospinal and intracortical excitability in patients with early untreated Parkinson’s disease represent differences in disease pathophysiology. Gender may also prove to be a relevant factor when choosing appropriate treatment,” said Dr. Kojovic.

EAN Develops Guideline on Palliative Care of Patients With Severe MS

A cohort of 934 individuals affected by multiple sclerosis (MS) from seven European countries played an instrumental part in developing the European Academy of Neurology’s (EAN) new guideline on palliative care for people with severe MS. “There were 751 MS patients and 183 caregiver relatives involved,” said Sascha Köpke, PhD, Professor of Nursing Research at the University of Lübeck in Germany.

With the involvement of patients and their families in a new guideline, the EAN is emphasizing shared decision-making as an increasingly important concept that underscores patient autonomy and promotes the individualization of diagnosis and therapy. According to this approach, patients and physicians undergo a detailed consultation and then choose the medical treatment. The EAN has supported this patient-centered approach for a long time, and it is becoming increasingly established in other medical areas as well.

“It was resource- and time-intensive to include consumers in the guideline process, but also highly rewarding,” said Prof. Köpke. “Patients and caregivers really helped us to formulate the guideline in a way that was in line with actual practice and their own needs. We were able to see clearly which of our ideas met with approval or rejection.” The comments were also instructive for the group of EAN experts. They raised new aspects as well as sensitive issues that had been left out of the first draft.

Two approaches were chosen to ensure that consumers would participate. “First, there was an international online survey launched by national MS societies following a trial run involving 20 patients and 18 caregivers. Second, we invited MS patients and caregiver relatives to focus group meetings,” said Prof. Köpke. The majority of participants approved the topics proposed by the EAN group of experts. About 98% agreed to incorporate the subject of multidisciplinary rehabilitation in the guideline. There were 569 free comments, of which 182 (32%) pertained to the specified topics. A further 227 comments (40%) addressed additional topics, of which 16 were pertinent to the guideline. Five of the focus group meetings corroborated the results of the online survey and helped to work out important issues for the individuals affected. “The involvement of patients and caregivers increases the reliability and relevance of the guideline for clinical practice,” said Prof. Köpke.

MIAMI—The sublingual apomorphine film APL-130277 (APL) is effective and well-tolerated for the acute management of off episodes in patients with Parkinson’s disease, according to research presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress.

APL is in development for the acute, intermittent treatment of off episodes associated with Parkinson’s disease, including end-of-dose wearing off (including early morning off); partial, delayed, or no on; and unpredictable off.

Evaluating the Efficacy and Safety of APL

To evaluate the efficacy and safety of APL, C. Warren Olanow, MD, Professor Emeritus and Chair Emeritus of Neurology and Professor of Neuroscience at the Mount Sinai School of Medicine in New York City, and colleagues conducted a double-blind, placebo-controlled trial.

Eligible participants were 18 or older, had idiopathic Parkinson’s disease according to UK Brain Bank criteria, were stage I–III according to the modified Hoehn and Yahr scale when on, and had a clinically meaningful response to levodopa with well-defined, early-morning off episodes. They had one or more off episodes per day and a total daily off time of two or more hours when receiving stable doses of levodopa qid or carbidopa–levodopa extended-release capsules tid for four or more weeks, or monoamine oxidase B inhibitors for eight or more weeks.

Patients with atypical or secondary parkinsonism, a major psychiatric disorder, or mouth cankers or sores were excluded. Patients who had undergone a neurosurgical procedure for Parkinson’s disease, received continuous subcutaneous apomorphine infusion, or received Duopa also were excluded. Finally, patients currently taking 5-HT3 antagonists, selective dopamine antagonists (excluding quetiapine or clozapine), or dopamine-depleting agents were excluded.

The APL dose (10 mg to 35 mg) to produce a full on was determined during the open-label titration phase. During the double-blind treatment phase, researchers randomized patients to the dose of APL identified during the titration phase or placebo that could be self-administered as many as five times per day for 12 weeks. Movement Disorder Society Unified Parkinson’s Disease Rating Scale, Part III (MDS-UPDRS-III) scores were determined monthly before dosing and at 15, 30, 45, 60, and 90 minutes post dose. The primary end point was the change in MDS-UPDRS-III score at 30 minutes post dose at 12 weeks. The key secondary end point was the percentage of patients with a patient-determined full on response within 30 minutes at 12 weeks. Safety assessments were also performed.

Treated Patients Were More Likely to Be On

A total of 109 patients were randomized to the double-blind treatment phase, and had a mean of 3.9 off episodes per day. Participants’ mean age was 62.7, and 37.6% of participants were female. More than 90% of participants were white.

In all, 80 patients completed the study. The least squares mean change from predose to 30 minutes post dose for the MDS-UPDRS-III score at 12 weeks was –11.1 and –3.5 for the APL and placebo groups, respectively (mean difference, –7.6). Similar results were observed at day 1 and weeks 4 and 8.

The difference between treatment arms in motor score became significant at 15 minutes and remained significant until 90 minutes. There was a significant difference favoring APL over placebo in the percentage of patients achieving a self-rated full on response at 30 minutes post dose at week 12. A home dosing diary showed that a larger percentage of patients receiving APL were on within 30 minutes post dose (least squares mean, 78.70%), compared with controls (least squares mean, 31.10%).

In the double-blind treatment phase, the overall discontinuation rate was 16.4% for placebo and 37.0% for APL. The discontinuation rate due to adverse events was 9.1% and 27.8% for placebo and APL, respectively. Discontinuation due to adverse events was the most common reason. During the double-blind treatment phase of APL, the most frequent adverse events were nausea (27.8%), somnolence (13%), and dizziness (9.3%). Most treatment-emergent adverse events were mild to moderate. Six patients experienced severe adverse events in the placebo and APL groups combined. Three patients experienced serious adverse events combined. One patient in the APL group died from cardiac arrest considered possibly related to treatment by the investigator. Oral adverse events occurred in 31.5% of patients in the APL group versus 7.3% of controls. These events were generally mild and reversible, said the researchers.

—Erica Tricarico

MIAMI—The sublingual apomorphine film APL-130277 (APL) is effective and well-tolerated for the acute management of off episodes in patients with Parkinson’s disease, according to research presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress.

APL is in development for the acute, intermittent treatment of off episodes associated with Parkinson’s disease, including end-of-dose wearing off (including early morning off); partial, delayed, or no on; and unpredictable off.

Evaluating the Efficacy and Safety of APL

To evaluate the efficacy and safety of APL, C. Warren Olanow, MD, Professor Emeritus and Chair Emeritus of Neurology and Professor of Neuroscience at the Mount Sinai School of Medicine in New York City, and colleagues conducted a double-blind, placebo-controlled trial.

Eligible participants were 18 or older, had idiopathic Parkinson’s disease according to UK Brain Bank criteria, were stage I–III according to the modified Hoehn and Yahr scale when on, and had a clinically meaningful response to levodopa with well-defined, early-morning off episodes. They had one or more off episodes per day and a total daily off time of two or more hours when receiving stable doses of levodopa qid or carbidopa–levodopa extended-release capsules tid for four or more weeks, or monoamine oxidase B inhibitors for eight or more weeks.

Patients with atypical or secondary parkinsonism, a major psychiatric disorder, or mouth cankers or sores were excluded. Patients who had undergone a neurosurgical procedure for Parkinson’s disease, received continuous subcutaneous apomorphine infusion, or received Duopa also were excluded. Finally, patients currently taking 5-HT3 antagonists, selective dopamine antagonists (excluding quetiapine or clozapine), or dopamine-depleting agents were excluded.

The APL dose (10 mg to 35 mg) to produce a full on was determined during the open-label titration phase. During the double-blind treatment phase, researchers randomized patients to the dose of APL identified during the titration phase or placebo that could be self-administered as many as five times per day for 12 weeks. Movement Disorder Society Unified Parkinson’s Disease Rating Scale, Part III (MDS-UPDRS-III) scores were determined monthly before dosing and at 15, 30, 45, 60, and 90 minutes post dose. The primary end point was the change in MDS-UPDRS-III score at 30 minutes post dose at 12 weeks. The key secondary end point was the percentage of patients with a patient-determined full on response within 30 minutes at 12 weeks. Safety assessments were also performed.

Treated Patients Were More Likely to Be On

A total of 109 patients were randomized to the double-blind treatment phase, and had a mean of 3.9 off episodes per day. Participants’ mean age was 62.7, and 37.6% of participants were female. More than 90% of participants were white.

In all, 80 patients completed the study. The least squares mean change from predose to 30 minutes post dose for the MDS-UPDRS-III score at 12 weeks was –11.1 and –3.5 for the APL and placebo groups, respectively (mean difference, –7.6). Similar results were observed at day 1 and weeks 4 and 8.

The difference between treatment arms in motor score became significant at 15 minutes and remained significant until 90 minutes. There was a significant difference favoring APL over placebo in the percentage of patients achieving a self-rated full on response at 30 minutes post dose at week 12. A home dosing diary showed that a larger percentage of patients receiving APL were on within 30 minutes post dose (least squares mean, 78.70%), compared with controls (least squares mean, 31.10%).

In the double-blind treatment phase, the overall discontinuation rate was 16.4% for placebo and 37.0% for APL. The discontinuation rate due to adverse events was 9.1% and 27.8% for placebo and APL, respectively. Discontinuation due to adverse events was the most common reason. During the double-blind treatment phase of APL, the most frequent adverse events were nausea (27.8%), somnolence (13%), and dizziness (9.3%). Most treatment-emergent adverse events were mild to moderate. Six patients experienced severe adverse events in the placebo and APL groups combined. Three patients experienced serious adverse events combined. One patient in the APL group died from cardiac arrest considered possibly related to treatment by the investigator. Oral adverse events occurred in 31.5% of patients in the APL group versus 7.3% of controls. These events were generally mild and reversible, said the researchers.

—Erica Tricarico

MIAMI—The sublingual apomorphine film APL-130277 (APL) is effective and well-tolerated for the acute management of off episodes in patients with Parkinson’s disease, according to research presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress.

APL is in development for the acute, intermittent treatment of off episodes associated with Parkinson’s disease, including end-of-dose wearing off (including early morning off); partial, delayed, or no on; and unpredictable off.

Evaluating the Efficacy and Safety of APL

To evaluate the efficacy and safety of APL, C. Warren Olanow, MD, Professor Emeritus and Chair Emeritus of Neurology and Professor of Neuroscience at the Mount Sinai School of Medicine in New York City, and colleagues conducted a double-blind, placebo-controlled trial.

Eligible participants were 18 or older, had idiopathic Parkinson’s disease according to UK Brain Bank criteria, were stage I–III according to the modified Hoehn and Yahr scale when on, and had a clinically meaningful response to levodopa with well-defined, early-morning off episodes. They had one or more off episodes per day and a total daily off time of two or more hours when receiving stable doses of levodopa qid or carbidopa–levodopa extended-release capsules tid for four or more weeks, or monoamine oxidase B inhibitors for eight or more weeks.

Patients with atypical or secondary parkinsonism, a major psychiatric disorder, or mouth cankers or sores were excluded. Patients who had undergone a neurosurgical procedure for Parkinson’s disease, received continuous subcutaneous apomorphine infusion, or received Duopa also were excluded. Finally, patients currently taking 5-HT3 antagonists, selective dopamine antagonists (excluding quetiapine or clozapine), or dopamine-depleting agents were excluded.

The APL dose (10 mg to 35 mg) to produce a full on was determined during the open-label titration phase. During the double-blind treatment phase, researchers randomized patients to the dose of APL identified during the titration phase or placebo that could be self-administered as many as five times per day for 12 weeks. Movement Disorder Society Unified Parkinson’s Disease Rating Scale, Part III (MDS-UPDRS-III) scores were determined monthly before dosing and at 15, 30, 45, 60, and 90 minutes post dose. The primary end point was the change in MDS-UPDRS-III score at 30 minutes post dose at 12 weeks. The key secondary end point was the percentage of patients with a patient-determined full on response within 30 minutes at 12 weeks. Safety assessments were also performed.

Treated Patients Were More Likely to Be On

A total of 109 patients were randomized to the double-blind treatment phase, and had a mean of 3.9 off episodes per day. Participants’ mean age was 62.7, and 37.6% of participants were female. More than 90% of participants were white.

In all, 80 patients completed the study. The least squares mean change from predose to 30 minutes post dose for the MDS-UPDRS-III score at 12 weeks was –11.1 and –3.5 for the APL and placebo groups, respectively (mean difference, –7.6). Similar results were observed at day 1 and weeks 4 and 8.

The difference between treatment arms in motor score became significant at 15 minutes and remained significant until 90 minutes. There was a significant difference favoring APL over placebo in the percentage of patients achieving a self-rated full on response at 30 minutes post dose at week 12. A home dosing diary showed that a larger percentage of patients receiving APL were on within 30 minutes post dose (least squares mean, 78.70%), compared with controls (least squares mean, 31.10%).

In the double-blind treatment phase, the overall discontinuation rate was 16.4% for placebo and 37.0% for APL. The discontinuation rate due to adverse events was 9.1% and 27.8% for placebo and APL, respectively. Discontinuation due to adverse events was the most common reason. During the double-blind treatment phase of APL, the most frequent adverse events were nausea (27.8%), somnolence (13%), and dizziness (9.3%). Most treatment-emergent adverse events were mild to moderate. Six patients experienced severe adverse events in the placebo and APL groups combined. Three patients experienced serious adverse events combined. One patient in the APL group died from cardiac arrest considered possibly related to treatment by the investigator. Oral adverse events occurred in 31.5% of patients in the APL group versus 7.3% of controls. These events were generally mild and reversible, said the researchers.

—Erica Tricarico

MIAMI—Droxidopa is associated with reductions in fall risk and dizziness or lightheadedness among users and nonusers of dopamine decarboxylase inhibitors (DDCIs), according to research described at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. These findings from an open-label, observational study “support previous data showing the efficacy of droxidopa for neurogenic orthostatic hypotension symptom reduction, even with concomitant DDCI use,” said the researchers.

Neurogenic orthostatic hypotension—a sustained blood pressure drop upon standing due to deficient norepinephrine release—is common among patients with disorders associated with autonomic nervous system dysfunction (eg, Parkinson’s disease, multiple system atrophy, and pure autonomic failure). Symptoms include lightheadedness or dizziness, presyncope, syncope, and falls.

A Post Hoc Analysis

To assess the long-term efficacy of droxidopa for the treatment of neurogenic orthostatic hypotension in patients concomitantly receiving DDCIs, Dr. Kymes and colleagues conducted a post hoc analysis of outcomes related to falls and neurogenic orthostatic hypotension symptoms in patients using DDCIs versus patients not using them. The researchers used data from a six-month open-label, prospective, observational study of patients newly initiating droxidopa.

Eligible participants were 18 and older; had underlying Parkinson’s disease, multiple system atrophy, pure autonomic failure, dopamine beta-hydroxylase deficiency, or nondiabetic autonomic neuropathy; were newly initiating droxidopa; and were able to speak and understand English. The researchers excluded patients with a self-reported diagnosis of dementia, Alzheimer disease, schizophrenia, or other psychiatric disorder, as well as those who were nonambulatory or confined to a wheelchair.

Researchers used a patient falls questionnaire to record the number of falls in the past month at baseline and at one, three, and six months. They also used the Orthostatic Hypotension Symptom Assessment (OHSA) Item I test to assess dizziness or lightheadedness. All outcomes were self-reported.

Investigators then compared baseline differences using chi-square tests for categorical variables and t-tests for continuous variables. “The influence of DDCIs on risk of falling and OHSA Item I scores was compared across time points using generalized linear mixed models (logistic for risk of falling) adjusting for repeated measures within individuals,” said the researchers.

Droxidopa Treatment Was Associated With Reduced Falls

A total of 168 patients were included in this study; 55 were DDCI users, and 113 were non-DDCI users. The mean age in the DDCI group was 75, and the mean age in the non-DDCI group was 57. There were 19 women (34.5%) in the DDCI user group and 68 (60.2%) in non-DDCI user group. Most participants were white in both groups (92.7% in the DDCI group and 81.4% in the non-DDCI group).

“There were significant differences in the primary diagnoses between the groups. Parkinson’s disease was the most frequent diagnosis in the DDCI group (89.1%), and autonomic failure with no cause identified was the most frequent diagnosis in the non-DDCI group (92.9%),” Dr. Kymes and colleagues said. “At baseline, 61.8% of patients receiving DDCIs and 46.9 % of patients not receiving DDCI reported at least one fall in the last month.” The mean OHSA Item I scores at baseline were 5 in the DDCI group and 6 in the non-DDCI group.

The proportion of patients receiving DDCIs who experienced one or more falls in the past month after six months of droxidopa treatment significantly decreased from baseline, with a 36.5% reduction over the course of the study.

Among patients not receiving a DDCI, there was a 6.2% reduction in falls over the course of the study, but the reduction was not significant. Changes in the proportion of patients reporting one or more falls in the past month from baseline to six months did not differ significantly between the groups.

In addition, patients receiving DDCIs and nonusers showed significant improvement in OHSA Item I scores from baseline after six months of droxidopa treatment (change of 1.5 and 1.9 units, respectively). The difference between groups was not statistically significant.

“Specifically designed studies are needed to further examine the impact of DDCIs on droxidopa because the current study sample was not powered for subgroup analyses and all data were self-reported by patients,” the researchers concluded.

—Erica Tricarico

MIAMI—Droxidopa is associated with reductions in fall risk and dizziness or lightheadedness among users and nonusers of dopamine decarboxylase inhibitors (DDCIs), according to research described at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. These findings from an open-label, observational study “support previous data showing the efficacy of droxidopa for neurogenic orthostatic hypotension symptom reduction, even with concomitant DDCI use,” said the researchers.

Neurogenic orthostatic hypotension—a sustained blood pressure drop upon standing due to deficient norepinephrine release—is common among patients with disorders associated with autonomic nervous system dysfunction (eg, Parkinson’s disease, multiple system atrophy, and pure autonomic failure). Symptoms include lightheadedness or dizziness, presyncope, syncope, and falls.

A Post Hoc Analysis

To assess the long-term efficacy of droxidopa for the treatment of neurogenic orthostatic hypotension in patients concomitantly receiving DDCIs, Dr. Kymes and colleagues conducted a post hoc analysis of outcomes related to falls and neurogenic orthostatic hypotension symptoms in patients using DDCIs versus patients not using them. The researchers used data from a six-month open-label, prospective, observational study of patients newly initiating droxidopa.

Eligible participants were 18 and older; had underlying Parkinson’s disease, multiple system atrophy, pure autonomic failure, dopamine beta-hydroxylase deficiency, or nondiabetic autonomic neuropathy; were newly initiating droxidopa; and were able to speak and understand English. The researchers excluded patients with a self-reported diagnosis of dementia, Alzheimer disease, schizophrenia, or other psychiatric disorder, as well as those who were nonambulatory or confined to a wheelchair.

Researchers used a patient falls questionnaire to record the number of falls in the past month at baseline and at one, three, and six months. They also used the Orthostatic Hypotension Symptom Assessment (OHSA) Item I test to assess dizziness or lightheadedness. All outcomes were self-reported.

Investigators then compared baseline differences using chi-square tests for categorical variables and t-tests for continuous variables. “The influence of DDCIs on risk of falling and OHSA Item I scores was compared across time points using generalized linear mixed models (logistic for risk of falling) adjusting for repeated measures within individuals,” said the researchers.

Droxidopa Treatment Was Associated With Reduced Falls

A total of 168 patients were included in this study; 55 were DDCI users, and 113 were non-DDCI users. The mean age in the DDCI group was 75, and the mean age in the non-DDCI group was 57. There were 19 women (34.5%) in the DDCI user group and 68 (60.2%) in non-DDCI user group. Most participants were white in both groups (92.7% in the DDCI group and 81.4% in the non-DDCI group).

“There were significant differences in the primary diagnoses between the groups. Parkinson’s disease was the most frequent diagnosis in the DDCI group (89.1%), and autonomic failure with no cause identified was the most frequent diagnosis in the non-DDCI group (92.9%),” Dr. Kymes and colleagues said. “At baseline, 61.8% of patients receiving DDCIs and 46.9 % of patients not receiving DDCI reported at least one fall in the last month.” The mean OHSA Item I scores at baseline were 5 in the DDCI group and 6 in the non-DDCI group.

The proportion of patients receiving DDCIs who experienced one or more falls in the past month after six months of droxidopa treatment significantly decreased from baseline, with a 36.5% reduction over the course of the study.

Among patients not receiving a DDCI, there was a 6.2% reduction in falls over the course of the study, but the reduction was not significant. Changes in the proportion of patients reporting one or more falls in the past month from baseline to six months did not differ significantly between the groups.

In addition, patients receiving DDCIs and nonusers showed significant improvement in OHSA Item I scores from baseline after six months of droxidopa treatment (change of 1.5 and 1.9 units, respectively). The difference between groups was not statistically significant.

“Specifically designed studies are needed to further examine the impact of DDCIs on droxidopa because the current study sample was not powered for subgroup analyses and all data were self-reported by patients,” the researchers concluded.

—Erica Tricarico

MIAMI—Droxidopa is associated with reductions in fall risk and dizziness or lightheadedness among users and nonusers of dopamine decarboxylase inhibitors (DDCIs), according to research described at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. These findings from an open-label, observational study “support previous data showing the efficacy of droxidopa for neurogenic orthostatic hypotension symptom reduction, even with concomitant DDCI use,” said the researchers.

Neurogenic orthostatic hypotension—a sustained blood pressure drop upon standing due to deficient norepinephrine release—is common among patients with disorders associated with autonomic nervous system dysfunction (eg, Parkinson’s disease, multiple system atrophy, and pure autonomic failure). Symptoms include lightheadedness or dizziness, presyncope, syncope, and falls.

A Post Hoc Analysis

To assess the long-term efficacy of droxidopa for the treatment of neurogenic orthostatic hypotension in patients concomitantly receiving DDCIs, Dr. Kymes and colleagues conducted a post hoc analysis of outcomes related to falls and neurogenic orthostatic hypotension symptoms in patients using DDCIs versus patients not using them. The researchers used data from a six-month open-label, prospective, observational study of patients newly initiating droxidopa.

Eligible participants were 18 and older; had underlying Parkinson’s disease, multiple system atrophy, pure autonomic failure, dopamine beta-hydroxylase deficiency, or nondiabetic autonomic neuropathy; were newly initiating droxidopa; and were able to speak and understand English. The researchers excluded patients with a self-reported diagnosis of dementia, Alzheimer disease, schizophrenia, or other psychiatric disorder, as well as those who were nonambulatory or confined to a wheelchair.

Researchers used a patient falls questionnaire to record the number of falls in the past month at baseline and at one, three, and six months. They also used the Orthostatic Hypotension Symptom Assessment (OHSA) Item I test to assess dizziness or lightheadedness. All outcomes were self-reported.

Investigators then compared baseline differences using chi-square tests for categorical variables and t-tests for continuous variables. “The influence of DDCIs on risk of falling and OHSA Item I scores was compared across time points using generalized linear mixed models (logistic for risk of falling) adjusting for repeated measures within individuals,” said the researchers.

Droxidopa Treatment Was Associated With Reduced Falls

A total of 168 patients were included in this study; 55 were DDCI users, and 113 were non-DDCI users. The mean age in the DDCI group was 75, and the mean age in the non-DDCI group was 57. There were 19 women (34.5%) in the DDCI user group and 68 (60.2%) in non-DDCI user group. Most participants were white in both groups (92.7% in the DDCI group and 81.4% in the non-DDCI group).

“There were significant differences in the primary diagnoses between the groups. Parkinson’s disease was the most frequent diagnosis in the DDCI group (89.1%), and autonomic failure with no cause identified was the most frequent diagnosis in the non-DDCI group (92.9%),” Dr. Kymes and colleagues said. “At baseline, 61.8% of patients receiving DDCIs and 46.9 % of patients not receiving DDCI reported at least one fall in the last month.” The mean OHSA Item I scores at baseline were 5 in the DDCI group and 6 in the non-DDCI group.

The proportion of patients receiving DDCIs who experienced one or more falls in the past month after six months of droxidopa treatment significantly decreased from baseline, with a 36.5% reduction over the course of the study.

Among patients not receiving a DDCI, there was a 6.2% reduction in falls over the course of the study, but the reduction was not significant. Changes in the proportion of patients reporting one or more falls in the past month from baseline to six months did not differ significantly between the groups.

In addition, patients receiving DDCIs and nonusers showed significant improvement in OHSA Item I scores from baseline after six months of droxidopa treatment (change of 1.5 and 1.9 units, respectively). The difference between groups was not statistically significant.

“Specifically designed studies are needed to further examine the impact of DDCIs on droxidopa because the current study sample was not powered for subgroup analyses and all data were self-reported by patients,” the researchers concluded.

—Erica Tricarico

MIAMI—Reduced cholinergic nucleus 4 (Ch4) density in Parkinson’s disease, as measured with MRI, is associated with deficits in attention, processing speed, and visuospatial function, according to research described at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. Ch4 density may serve as a surrogate imaging biomarker of cognition in early Parkinson’s disease, said the researchers.

Degeneration of the nucleus basalis of Meynert (NBM) contributes to dementia in Parkinson’s disease through a loss of cholinergic innervation to the neocortex. Cholinergic neurons of the NBM are in Ch4, a structure that can be measured with MRI techniques using cytoarchitectonic maps.

Evaluating Ch4 Density and Cognitive Performance

To determine whether Ch4 density, a proxy measure for NBM volume, is associated with cognitive test performance in de novo Parkinson’s disease, Cody S. Freeman, MD, a fellow at the University of Virginia School of Medicine in Charlottesville, and colleagues analyzed baseline brain MRIs and neuropsychologic test scores for 228 patients with Parkinson’s disease and 101 healthy controls from the Parkinson’s Progression Markers Initiative (PPMI). They also analyzed brain MRIs and neuropsychologic test scores at four years for a subset of 92 participants with Parkinson’s disease in the PPMI.

Neuropsychologic testing included the Montreal Cognitive Assessment (MoCA), Hopkins Verbal Learning Test (HVLT), Judgment of Line Orientation (JLO), Letter Number Sequencing (LNS), Symbol Digit Modalities Test (SDMT), and semantic fluency (animals).

The researchers used MP-RAGE T1 sequences and a probabilistic atlas from the reference Montreal Neurological Institute single subject brain to apply voxel-based morphometry methods to determine Ch4 density. In addition, they used correlation coefficients and linear regression models to analyze relationships between Ch4 density and cognitive scores.

Ch4 Density Was Significantly Associated With Higher MoCA Scores

At baseline, 33.7% of healthy controls and 38.2% of patients with Parkinson’s disease were female. The mean age at neurologic testing was 59.5 among healthy controls and 61.0 in the Parkinson’s disease cohort. The median MoCA score was 28 for controls and patients with Parkinson’s disease at baseline. The mean Ch4 density was 87.9 in the control group and 86.4 in the Parkinson’s disease cohort.

At baseline, Ch4 density was significantly correlated with MoCA, JLO, LNS, and SDMT scores. In a linear regression model adjusted for age and sex, Ch4 density was significantly associated with higher MoCA scores in patients with Parkinson’s disease. In linear regression models adjusted for sex, increasing Ch4 density was associated with higher JLO, LNS, and SDMT scores. The researchers observed no associations between Ch4 density and JLO and semantic fluency in linear regression models adjusted for sex.

For the subset of participants with Parkinson’s disease with brain MRI and neuropsychologic testing available at four years, Ch4 density was significantly correlated with MoCA, JLO, LNS, and SDMT. In a linear regression model adjusted for age and sex, increasing Ch4 density was associated with higher MoCA scores in patients with Parkinson’s disease. In linear regression models adjusted for sex, increasing Ch4 density was associated with higher JLO, LNS, and SDMT scores.

MIAMI—Reduced cholinergic nucleus 4 (Ch4) density in Parkinson’s disease, as measured with MRI, is associated with deficits in attention, processing speed, and visuospatial function, according to research described at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. Ch4 density may serve as a surrogate imaging biomarker of cognition in early Parkinson’s disease, said the researchers.

Degeneration of the nucleus basalis of Meynert (NBM) contributes to dementia in Parkinson’s disease through a loss of cholinergic innervation to the neocortex. Cholinergic neurons of the NBM are in Ch4, a structure that can be measured with MRI techniques using cytoarchitectonic maps.

Evaluating Ch4 Density and Cognitive Performance

To determine whether Ch4 density, a proxy measure for NBM volume, is associated with cognitive test performance in de novo Parkinson’s disease, Cody S. Freeman, MD, a fellow at the University of Virginia School of Medicine in Charlottesville, and colleagues analyzed baseline brain MRIs and neuropsychologic test scores for 228 patients with Parkinson’s disease and 101 healthy controls from the Parkinson’s Progression Markers Initiative (PPMI). They also analyzed brain MRIs and neuropsychologic test scores at four years for a subset of 92 participants with Parkinson’s disease in the PPMI.

Neuropsychologic testing included the Montreal Cognitive Assessment (MoCA), Hopkins Verbal Learning Test (HVLT), Judgment of Line Orientation (JLO), Letter Number Sequencing (LNS), Symbol Digit Modalities Test (SDMT), and semantic fluency (animals).

The researchers used MP-RAGE T1 sequences and a probabilistic atlas from the reference Montreal Neurological Institute single subject brain to apply voxel-based morphometry methods to determine Ch4 density. In addition, they used correlation coefficients and linear regression models to analyze relationships between Ch4 density and cognitive scores.

Ch4 Density Was Significantly Associated With Higher MoCA Scores

At baseline, 33.7% of healthy controls and 38.2% of patients with Parkinson’s disease were female. The mean age at neurologic testing was 59.5 among healthy controls and 61.0 in the Parkinson’s disease cohort. The median MoCA score was 28 for controls and patients with Parkinson’s disease at baseline. The mean Ch4 density was 87.9 in the control group and 86.4 in the Parkinson’s disease cohort.

At baseline, Ch4 density was significantly correlated with MoCA, JLO, LNS, and SDMT scores. In a linear regression model adjusted for age and sex, Ch4 density was significantly associated with higher MoCA scores in patients with Parkinson’s disease. In linear regression models adjusted for sex, increasing Ch4 density was associated with higher JLO, LNS, and SDMT scores. The researchers observed no associations between Ch4 density and JLO and semantic fluency in linear regression models adjusted for sex.

For the subset of participants with Parkinson’s disease with brain MRI and neuropsychologic testing available at four years, Ch4 density was significantly correlated with MoCA, JLO, LNS, and SDMT. In a linear regression model adjusted for age and sex, increasing Ch4 density was associated with higher MoCA scores in patients with Parkinson’s disease. In linear regression models adjusted for sex, increasing Ch4 density was associated with higher JLO, LNS, and SDMT scores.

MIAMI—Reduced cholinergic nucleus 4 (Ch4) density in Parkinson’s disease, as measured with MRI, is associated with deficits in attention, processing speed, and visuospatial function, according to research described at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. Ch4 density may serve as a surrogate imaging biomarker of cognition in early Parkinson’s disease, said the researchers.

Degeneration of the nucleus basalis of Meynert (NBM) contributes to dementia in Parkinson’s disease through a loss of cholinergic innervation to the neocortex. Cholinergic neurons of the NBM are in Ch4, a structure that can be measured with MRI techniques using cytoarchitectonic maps.

Evaluating Ch4 Density and Cognitive Performance

To determine whether Ch4 density, a proxy measure for NBM volume, is associated with cognitive test performance in de novo Parkinson’s disease, Cody S. Freeman, MD, a fellow at the University of Virginia School of Medicine in Charlottesville, and colleagues analyzed baseline brain MRIs and neuropsychologic test scores for 228 patients with Parkinson’s disease and 101 healthy controls from the Parkinson’s Progression Markers Initiative (PPMI). They also analyzed brain MRIs and neuropsychologic test scores at four years for a subset of 92 participants with Parkinson’s disease in the PPMI.

Neuropsychologic testing included the Montreal Cognitive Assessment (MoCA), Hopkins Verbal Learning Test (HVLT), Judgment of Line Orientation (JLO), Letter Number Sequencing (LNS), Symbol Digit Modalities Test (SDMT), and semantic fluency (animals).

The researchers used MP-RAGE T1 sequences and a probabilistic atlas from the reference Montreal Neurological Institute single subject brain to apply voxel-based morphometry methods to determine Ch4 density. In addition, they used correlation coefficients and linear regression models to analyze relationships between Ch4 density and cognitive scores.

Ch4 Density Was Significantly Associated With Higher MoCA Scores

At baseline, 33.7% of healthy controls and 38.2% of patients with Parkinson’s disease were female. The mean age at neurologic testing was 59.5 among healthy controls and 61.0 in the Parkinson’s disease cohort. The median MoCA score was 28 for controls and patients with Parkinson’s disease at baseline. The mean Ch4 density was 87.9 in the control group and 86.4 in the Parkinson’s disease cohort.

At baseline, Ch4 density was significantly correlated with MoCA, JLO, LNS, and SDMT scores. In a linear regression model adjusted for age and sex, Ch4 density was significantly associated with higher MoCA scores in patients with Parkinson’s disease. In linear regression models adjusted for sex, increasing Ch4 density was associated with higher JLO, LNS, and SDMT scores. The researchers observed no associations between Ch4 density and JLO and semantic fluency in linear regression models adjusted for sex.

For the subset of participants with Parkinson’s disease with brain MRI and neuropsychologic testing available at four years, Ch4 density was significantly correlated with MoCA, JLO, LNS, and SDMT. In a linear regression model adjusted for age and sex, increasing Ch4 density was associated with higher MoCA scores in patients with Parkinson’s disease. In linear regression models adjusted for sex, increasing Ch4 density was associated with higher JLO, LNS, and SDMT scores.