Parkinson's Disease

An incisionless surgical procedure that uses focused ultrasound ablation (FUSA) to target the globus pallidus internus of patients with Parkinson’s disease significantly reduced tremors and improved mobility for those with advanced disease, new research shows.

The technique requires no sedation or brain implants. Surgeons use MRI to identify the globus pallidus internus, a part of the basal ganglia involved in movement disorders, and a focused ultrasound beam to heat and destroy the tissue.

Investigators performed the procedure with a device called Exablate Neuro, which was first approved by the Food and Drug Administration in 2016 to treat essential tremor.

On the basis of the results of a multicenter, randomized, sham-controlled trial, the agency expanded the indication in 2021 to include unilateral pallidotomy to treat advanced Parkinson’s disease for patients with mobility, rigidity, or dyskinesia symptoms.

“In some patients with Parkinson’s disease, you get dyskinesias, and ablation of the globus pallidus significantly reduces those dyskinesias and motor impairment,” said lead investigator Vibhor Krishna, MD, associate professor of neurosurgery at the University of North Carolina at Chapel Hill. “It could be used to treat patients when other surgical procedures can’t be applied.”

The study was published online in the New England Journal of Medicine.
 

Strong response

For the study, 94 patients with advanced Parkinson’s disease who had dyskinesias or motor fluctuations and motor impairment in the off-medication state wore transducer helmets while lying in an MRI scanner. Patients were awake during the entire procedure.

The treatment group received unilateral FUSA on the side of the brain with the greatest motor impairment. The device initially delivered target temperatures of 40°-45° C. Ablative temperatures were gradually increased following evaluations to test for improvement of motor symptoms. The maximum temperature used was 54.3° C.

Patients in the control group underwent an identical procedure with the sonication energy disabled.

The primary outcome was a response to therapy at 3 months, defined as a decrease of at least three points from baseline either in the score on the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), part III, while off medication or in the score on the Unified Dyskinesia Rating Scale (UDRS) while on medication.

At 3 months, 69% of the treatment group reported a response, compared with 32% of the control group (P = .003).

When researchers analyzed MDS-UPDRS scores, they found that 29% of the treatment group and 27% of the control group showed improvement. For UDRS scores, 12% of the treatment group demonstrated improvement. In the control group, there was no improvement on this score. Improvements in both scores were reported in 28% of the treatment group and 5% of the control group.

Among those who reported a response at 3 months, 77% continued to show a response at 12 months.
 

‘Unforgiving’ area of the brain

While the response rate was a promising sign of this finding, it was not what interested Dr. Krishna the most. “The most surprising finding of this trial is how safe focused ultrasound pallidotomy is in treating patients with Parkinson’s disease,” he said.

The globus pallidus internus is an area of the brain that Dr. Krishna calls “unforgiving.”

“One side is motor fibers, and any problem with that can paralyze the patient, and just below that is the optic tract, and any problem there, you would lose vision,” Dr. Krishna said. “It is a very tough neighborhood to be in.”

By using MRI-guided ultrasound, surgeons can change the target and temperature of the ultrasound beam during the procedure to allow more precise treatment.

Pallidotomy-related adverse events in the treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness. All were mild to moderate, Dr. Krishna said.
 

More study is needed

Dyskinesia is a challenge in the management of Parkinson’s disease. Patients need antiparkinsonian medications to slow deterioration of motor function, but those medications can cause the involuntary movements that are a hallmark of dyskinesia.

The most common treatment for this complication, deep-brain stimulation (DBS), has its own drawbacks. It’s an open procedure, and there is a low-level risk for intracranial bleeding and infection. In addition, the electrode implants require ongoing maintenance and adjustment.

But the findings of this study show that, for patients who aren’t candidates for other therapies, such as DBS and ablative radiofrequency, FUSA may be an alternative, wrote Anette Schrag, PhD, professor of clinical neurosciences at University College London, in an accompanying commentary.

“The results confirm that it is effective in reducing motor complications of Parkinson’s disease, at least in the short term,” Dr. Schrag wrote. However, more long-term studies are needed, she added.

One-third of patients in the treatment group had no response to the treatment, and investigators aren’t sure why. Dr. Krishna noted that the benefits of the procedure waned in about a quarter of patients within a year of treatment.

Investigators plan to probe these questions in future trials.

“The results of this trial are promising,” Dr. Schrag wrote, “but given the nonreversible nature of the intervention and the progressive nature of the disease, it will be important to establish whether improvements in motor complications are maintained over longer periods and whether treatment results in improved overall functioning and quality of life for patients.”

The study was funded by Insightec. Disclosure forms for Dr. Krishna and Dr. Schrag are provided on the journal’s website.

A version of this article originally appeared on Medscape.com.

An incisionless surgical procedure that uses focused ultrasound ablation (FUSA) to target the globus pallidus internus of patients with Parkinson’s disease significantly reduced tremors and improved mobility for those with advanced disease, new research shows.

The technique requires no sedation or brain implants. Surgeons use MRI to identify the globus pallidus internus, a part of the basal ganglia involved in movement disorders, and a focused ultrasound beam to heat and destroy the tissue.

Investigators performed the procedure with a device called Exablate Neuro, which was first approved by the Food and Drug Administration in 2016 to treat essential tremor.

On the basis of the results of a multicenter, randomized, sham-controlled trial, the agency expanded the indication in 2021 to include unilateral pallidotomy to treat advanced Parkinson’s disease for patients with mobility, rigidity, or dyskinesia symptoms.

“In some patients with Parkinson’s disease, you get dyskinesias, and ablation of the globus pallidus significantly reduces those dyskinesias and motor impairment,” said lead investigator Vibhor Krishna, MD, associate professor of neurosurgery at the University of North Carolina at Chapel Hill. “It could be used to treat patients when other surgical procedures can’t be applied.”

The study was published online in the New England Journal of Medicine.
 

Strong response

For the study, 94 patients with advanced Parkinson’s disease who had dyskinesias or motor fluctuations and motor impairment in the off-medication state wore transducer helmets while lying in an MRI scanner. Patients were awake during the entire procedure.

The treatment group received unilateral FUSA on the side of the brain with the greatest motor impairment. The device initially delivered target temperatures of 40°-45° C. Ablative temperatures were gradually increased following evaluations to test for improvement of motor symptoms. The maximum temperature used was 54.3° C.

Patients in the control group underwent an identical procedure with the sonication energy disabled.

The primary outcome was a response to therapy at 3 months, defined as a decrease of at least three points from baseline either in the score on the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), part III, while off medication or in the score on the Unified Dyskinesia Rating Scale (UDRS) while on medication.

At 3 months, 69% of the treatment group reported a response, compared with 32% of the control group (P = .003).

When researchers analyzed MDS-UPDRS scores, they found that 29% of the treatment group and 27% of the control group showed improvement. For UDRS scores, 12% of the treatment group demonstrated improvement. In the control group, there was no improvement on this score. Improvements in both scores were reported in 28% of the treatment group and 5% of the control group.

Among those who reported a response at 3 months, 77% continued to show a response at 12 months.
 

‘Unforgiving’ area of the brain

While the response rate was a promising sign of this finding, it was not what interested Dr. Krishna the most. “The most surprising finding of this trial is how safe focused ultrasound pallidotomy is in treating patients with Parkinson’s disease,” he said.

The globus pallidus internus is an area of the brain that Dr. Krishna calls “unforgiving.”

“One side is motor fibers, and any problem with that can paralyze the patient, and just below that is the optic tract, and any problem there, you would lose vision,” Dr. Krishna said. “It is a very tough neighborhood to be in.”

By using MRI-guided ultrasound, surgeons can change the target and temperature of the ultrasound beam during the procedure to allow more precise treatment.

Pallidotomy-related adverse events in the treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness. All were mild to moderate, Dr. Krishna said.
 

More study is needed

Dyskinesia is a challenge in the management of Parkinson’s disease. Patients need antiparkinsonian medications to slow deterioration of motor function, but those medications can cause the involuntary movements that are a hallmark of dyskinesia.

The most common treatment for this complication, deep-brain stimulation (DBS), has its own drawbacks. It’s an open procedure, and there is a low-level risk for intracranial bleeding and infection. In addition, the electrode implants require ongoing maintenance and adjustment.

But the findings of this study show that, for patients who aren’t candidates for other therapies, such as DBS and ablative radiofrequency, FUSA may be an alternative, wrote Anette Schrag, PhD, professor of clinical neurosciences at University College London, in an accompanying commentary.

“The results confirm that it is effective in reducing motor complications of Parkinson’s disease, at least in the short term,” Dr. Schrag wrote. However, more long-term studies are needed, she added.

One-third of patients in the treatment group had no response to the treatment, and investigators aren’t sure why. Dr. Krishna noted that the benefits of the procedure waned in about a quarter of patients within a year of treatment.

Investigators plan to probe these questions in future trials.

“The results of this trial are promising,” Dr. Schrag wrote, “but given the nonreversible nature of the intervention and the progressive nature of the disease, it will be important to establish whether improvements in motor complications are maintained over longer periods and whether treatment results in improved overall functioning and quality of life for patients.”

The study was funded by Insightec. Disclosure forms for Dr. Krishna and Dr. Schrag are provided on the journal’s website.

A version of this article originally appeared on Medscape.com.

An incisionless surgical procedure that uses focused ultrasound ablation (FUSA) to target the globus pallidus internus of patients with Parkinson’s disease significantly reduced tremors and improved mobility for those with advanced disease, new research shows.

The technique requires no sedation or brain implants. Surgeons use MRI to identify the globus pallidus internus, a part of the basal ganglia involved in movement disorders, and a focused ultrasound beam to heat and destroy the tissue.

Investigators performed the procedure with a device called Exablate Neuro, which was first approved by the Food and Drug Administration in 2016 to treat essential tremor.

On the basis of the results of a multicenter, randomized, sham-controlled trial, the agency expanded the indication in 2021 to include unilateral pallidotomy to treat advanced Parkinson’s disease for patients with mobility, rigidity, or dyskinesia symptoms.

“In some patients with Parkinson’s disease, you get dyskinesias, and ablation of the globus pallidus significantly reduces those dyskinesias and motor impairment,” said lead investigator Vibhor Krishna, MD, associate professor of neurosurgery at the University of North Carolina at Chapel Hill. “It could be used to treat patients when other surgical procedures can’t be applied.”

The study was published online in the New England Journal of Medicine.
 

Strong response

For the study, 94 patients with advanced Parkinson’s disease who had dyskinesias or motor fluctuations and motor impairment in the off-medication state wore transducer helmets while lying in an MRI scanner. Patients were awake during the entire procedure.

The treatment group received unilateral FUSA on the side of the brain with the greatest motor impairment. The device initially delivered target temperatures of 40°-45° C. Ablative temperatures were gradually increased following evaluations to test for improvement of motor symptoms. The maximum temperature used was 54.3° C.

Patients in the control group underwent an identical procedure with the sonication energy disabled.

The primary outcome was a response to therapy at 3 months, defined as a decrease of at least three points from baseline either in the score on the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), part III, while off medication or in the score on the Unified Dyskinesia Rating Scale (UDRS) while on medication.

At 3 months, 69% of the treatment group reported a response, compared with 32% of the control group (P = .003).

When researchers analyzed MDS-UPDRS scores, they found that 29% of the treatment group and 27% of the control group showed improvement. For UDRS scores, 12% of the treatment group demonstrated improvement. In the control group, there was no improvement on this score. Improvements in both scores were reported in 28% of the treatment group and 5% of the control group.

Among those who reported a response at 3 months, 77% continued to show a response at 12 months.
 

‘Unforgiving’ area of the brain

While the response rate was a promising sign of this finding, it was not what interested Dr. Krishna the most. “The most surprising finding of this trial is how safe focused ultrasound pallidotomy is in treating patients with Parkinson’s disease,” he said.

The globus pallidus internus is an area of the brain that Dr. Krishna calls “unforgiving.”

“One side is motor fibers, and any problem with that can paralyze the patient, and just below that is the optic tract, and any problem there, you would lose vision,” Dr. Krishna said. “It is a very tough neighborhood to be in.”

By using MRI-guided ultrasound, surgeons can change the target and temperature of the ultrasound beam during the procedure to allow more precise treatment.

Pallidotomy-related adverse events in the treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness. All were mild to moderate, Dr. Krishna said.
 

More study is needed

Dyskinesia is a challenge in the management of Parkinson’s disease. Patients need antiparkinsonian medications to slow deterioration of motor function, but those medications can cause the involuntary movements that are a hallmark of dyskinesia.

The most common treatment for this complication, deep-brain stimulation (DBS), has its own drawbacks. It’s an open procedure, and there is a low-level risk for intracranial bleeding and infection. In addition, the electrode implants require ongoing maintenance and adjustment.

But the findings of this study show that, for patients who aren’t candidates for other therapies, such as DBS and ablative radiofrequency, FUSA may be an alternative, wrote Anette Schrag, PhD, professor of clinical neurosciences at University College London, in an accompanying commentary.

“The results confirm that it is effective in reducing motor complications of Parkinson’s disease, at least in the short term,” Dr. Schrag wrote. However, more long-term studies are needed, she added.

One-third of patients in the treatment group had no response to the treatment, and investigators aren’t sure why. Dr. Krishna noted that the benefits of the procedure waned in about a quarter of patients within a year of treatment.

Investigators plan to probe these questions in future trials.

“The results of this trial are promising,” Dr. Schrag wrote, “but given the nonreversible nature of the intervention and the progressive nature of the disease, it will be important to establish whether improvements in motor complications are maintained over longer periods and whether treatment results in improved overall functioning and quality of life for patients.”

The study was funded by Insightec. Disclosure forms for Dr. Krishna and Dr. Schrag are provided on the journal’s website.

A version of this article originally appeared on Medscape.com.

Children who suffer from persistent bad dreams may be at increased risk for cognitive impairment or Parkinson’s disease (PD) later in life, new research shows.

Compared with children who never had distressing dreams between ages 7 and 11 years, those who had persistent distressing dreams were 76% more likely to develop cognitive impairment and roughly seven times more likely to develop PD by age 50 years.

It’s been shown previously that sleep problems in adulthood, including distressing dreams, can precede the onset of neurodegenerative diseases such as Alzheimer’s disease (AD) or PD by several years, and in some cases decades, study investigator Abidemi Otaiku, BMBS, University of Birmingham (England), told this news organization.

However, no studies have investigated whether distressing dreams during childhood might also be associated with increased risk for cognitive decline or PD.

“As such, these findings provide evidence for the first time that certain sleep problems in childhood (having regular distressing dreams) could be an early indicator of increased dementia and PD risk,” Dr. Otaiku said.

He noted that the findings build on previous studies which showed that regular nightmares in childhood could be an early indicator for psychiatric problems in adolescence, such as borderline personality disorder, attention-deficit/hyperactivity disorder, and psychosis.

The study was published online February 26 in The Lancet journal eClinicalMedicine.

Statistically significant

The prospective, longitudinal analysis used data from the 1958 British Birth Cohort Study, a prospective birth cohort which included all people born in Britain during a single week in 1958.

At age 7 years (in 1965) and 11 years (in 1969), mothers were asked to report whether their child experienced “bad dreams or night terrors” in the past 3 months, and cognitive impairment and PD were determined at age 50 (2008).

Among a total of 6,991 children (51% girls), 78.2% never had distressing dreams, 17.9% had transient distressing dreams (either at ages 7 or 11 years), and 3.8% had persistent distressing dreams (at both ages 7 and 11 years).

By age 50, 262 participants had developed cognitive impairment, and five had been diagnosed with PD.

After adjusting for all covariates, having more regular distressing dreams during childhood was “linearly and statistically significantly” associated with higher risk of developing cognitive impairment or PD by age 50 years (P = .037). This was the case in both boys and girls.

Compared with children who never had bad dreams, peers who had persistent distressing dreams (at ages 7 and 11 years) had an 85% increased risk for cognitive impairment or PD by age 50 (adjusted odds ratio, 1.85; 95% confidence interval, 1.10-3.11; P = .019).

The associations remained when incident cognitive impairment and incident PD were analyzed separately.

Compared with children who never had distressing dreams, children who had persistent distressing dreams were 76% more likely to develop cognitive impairment by age 50 years (aOR, 1.76; 95% CI, 1.03-2.99; P = .037), and were about seven times more likely to be diagnosed with PD by age 50 years (aOR, 7.35; 95% CI, 1.03-52.73; P = .047).

The linear association was statistically significant for PD (P = .050) and had a trend toward statistical significance for cognitive impairment (P = .074).

Mechanism unclear

“Early-life nightmares might be causally associated with cognitive impairment and PD, noncausally associated with cognitive impairment and PD, or both. At this stage it remains unclear which of the three options is correct. Therefore, further research on mechanisms is needed,” Dr. Otaiku told this news organization.

“One plausible noncausal explanation is that there are shared genetic factors which predispose individuals to having frequent nightmares in childhood, and to developing neurodegenerative diseases such as AD or PD in adulthood,” he added.

It’s also plausible that having regular nightmares throughout childhood could be a causal risk factor for cognitive impairment and PD by causing chronic sleep disruption, he noted.

“Chronic sleep disruption due to nightmares might lead to impaired glymphatic clearance during sleep – and thus greater accumulation of pathological proteins in the brain, such as amyloid-beta and alpha-synuclein,” Dr. Otaiku said.

Disrupted sleep throughout childhood might also impair normal brain development, which could make children’s brains less resilient to neuropathologic damage, he said.

Clinical implications?

There are established treatments for childhood nightmares, including nonpharmacologic approaches.

“For children who have regular nightmares that lead to impaired daytime functioning, it may well be a good idea for them to see a sleep physician to discuss whether treatment may be needed,” Dr. Otaiku said.

But should doctors treat children with persistent nightmares for the purpose of preventing neurodegenerative diseases in adulthood or psychiatric problems in adolescence?

“It’s an interesting possibility. However, more research is needed to confirm these epidemiological associations and to determine whether or not nightmares are a causal risk factor for these conditions,” Dr. Otaiku concluded.

The study received no external funding. Dr. Otaiku reports no relevant disclosures.

A version of this article first appeared on Medscape.com.

Children who suffer from persistent bad dreams may be at increased risk for cognitive impairment or Parkinson’s disease (PD) later in life, new research shows.

Compared with children who never had distressing dreams between ages 7 and 11 years, those who had persistent distressing dreams were 76% more likely to develop cognitive impairment and roughly seven times more likely to develop PD by age 50 years.

It’s been shown previously that sleep problems in adulthood, including distressing dreams, can precede the onset of neurodegenerative diseases such as Alzheimer’s disease (AD) or PD by several years, and in some cases decades, study investigator Abidemi Otaiku, BMBS, University of Birmingham (England), told this news organization.

However, no studies have investigated whether distressing dreams during childhood might also be associated with increased risk for cognitive decline or PD.

“As such, these findings provide evidence for the first time that certain sleep problems in childhood (having regular distressing dreams) could be an early indicator of increased dementia and PD risk,” Dr. Otaiku said.

He noted that the findings build on previous studies which showed that regular nightmares in childhood could be an early indicator for psychiatric problems in adolescence, such as borderline personality disorder, attention-deficit/hyperactivity disorder, and psychosis.

The study was published online February 26 in The Lancet journal eClinicalMedicine.

Statistically significant

The prospective, longitudinal analysis used data from the 1958 British Birth Cohort Study, a prospective birth cohort which included all people born in Britain during a single week in 1958.

At age 7 years (in 1965) and 11 years (in 1969), mothers were asked to report whether their child experienced “bad dreams or night terrors” in the past 3 months, and cognitive impairment and PD were determined at age 50 (2008).

Among a total of 6,991 children (51% girls), 78.2% never had distressing dreams, 17.9% had transient distressing dreams (either at ages 7 or 11 years), and 3.8% had persistent distressing dreams (at both ages 7 and 11 years).

By age 50, 262 participants had developed cognitive impairment, and five had been diagnosed with PD.

After adjusting for all covariates, having more regular distressing dreams during childhood was “linearly and statistically significantly” associated with higher risk of developing cognitive impairment or PD by age 50 years (P = .037). This was the case in both boys and girls.

Compared with children who never had bad dreams, peers who had persistent distressing dreams (at ages 7 and 11 years) had an 85% increased risk for cognitive impairment or PD by age 50 (adjusted odds ratio, 1.85; 95% confidence interval, 1.10-3.11; P = .019).

The associations remained when incident cognitive impairment and incident PD were analyzed separately.

Compared with children who never had distressing dreams, children who had persistent distressing dreams were 76% more likely to develop cognitive impairment by age 50 years (aOR, 1.76; 95% CI, 1.03-2.99; P = .037), and were about seven times more likely to be diagnosed with PD by age 50 years (aOR, 7.35; 95% CI, 1.03-52.73; P = .047).

The linear association was statistically significant for PD (P = .050) and had a trend toward statistical significance for cognitive impairment (P = .074).

Mechanism unclear

“Early-life nightmares might be causally associated with cognitive impairment and PD, noncausally associated with cognitive impairment and PD, or both. At this stage it remains unclear which of the three options is correct. Therefore, further research on mechanisms is needed,” Dr. Otaiku told this news organization.

“One plausible noncausal explanation is that there are shared genetic factors which predispose individuals to having frequent nightmares in childhood, and to developing neurodegenerative diseases such as AD or PD in adulthood,” he added.

It’s also plausible that having regular nightmares throughout childhood could be a causal risk factor for cognitive impairment and PD by causing chronic sleep disruption, he noted.

“Chronic sleep disruption due to nightmares might lead to impaired glymphatic clearance during sleep – and thus greater accumulation of pathological proteins in the brain, such as amyloid-beta and alpha-synuclein,” Dr. Otaiku said.

Disrupted sleep throughout childhood might also impair normal brain development, which could make children’s brains less resilient to neuropathologic damage, he said.

Clinical implications?

There are established treatments for childhood nightmares, including nonpharmacologic approaches.

“For children who have regular nightmares that lead to impaired daytime functioning, it may well be a good idea for them to see a sleep physician to discuss whether treatment may be needed,” Dr. Otaiku said.

But should doctors treat children with persistent nightmares for the purpose of preventing neurodegenerative diseases in adulthood or psychiatric problems in adolescence?

“It’s an interesting possibility. However, more research is needed to confirm these epidemiological associations and to determine whether or not nightmares are a causal risk factor for these conditions,” Dr. Otaiku concluded.

The study received no external funding. Dr. Otaiku reports no relevant disclosures.

A version of this article first appeared on Medscape.com.

Children who suffer from persistent bad dreams may be at increased risk for cognitive impairment or Parkinson’s disease (PD) later in life, new research shows.

Compared with children who never had distressing dreams between ages 7 and 11 years, those who had persistent distressing dreams were 76% more likely to develop cognitive impairment and roughly seven times more likely to develop PD by age 50 years.

It’s been shown previously that sleep problems in adulthood, including distressing dreams, can precede the onset of neurodegenerative diseases such as Alzheimer’s disease (AD) or PD by several years, and in some cases decades, study investigator Abidemi Otaiku, BMBS, University of Birmingham (England), told this news organization.

However, no studies have investigated whether distressing dreams during childhood might also be associated with increased risk for cognitive decline or PD.

“As such, these findings provide evidence for the first time that certain sleep problems in childhood (having regular distressing dreams) could be an early indicator of increased dementia and PD risk,” Dr. Otaiku said.

He noted that the findings build on previous studies which showed that regular nightmares in childhood could be an early indicator for psychiatric problems in adolescence, such as borderline personality disorder, attention-deficit/hyperactivity disorder, and psychosis.

The study was published online February 26 in The Lancet journal eClinicalMedicine.

Statistically significant

The prospective, longitudinal analysis used data from the 1958 British Birth Cohort Study, a prospective birth cohort which included all people born in Britain during a single week in 1958.

At age 7 years (in 1965) and 11 years (in 1969), mothers were asked to report whether their child experienced “bad dreams or night terrors” in the past 3 months, and cognitive impairment and PD were determined at age 50 (2008).

Among a total of 6,991 children (51% girls), 78.2% never had distressing dreams, 17.9% had transient distressing dreams (either at ages 7 or 11 years), and 3.8% had persistent distressing dreams (at both ages 7 and 11 years).

By age 50, 262 participants had developed cognitive impairment, and five had been diagnosed with PD.

After adjusting for all covariates, having more regular distressing dreams during childhood was “linearly and statistically significantly” associated with higher risk of developing cognitive impairment or PD by age 50 years (P = .037). This was the case in both boys and girls.

Compared with children who never had bad dreams, peers who had persistent distressing dreams (at ages 7 and 11 years) had an 85% increased risk for cognitive impairment or PD by age 50 (adjusted odds ratio, 1.85; 95% confidence interval, 1.10-3.11; P = .019).

The associations remained when incident cognitive impairment and incident PD were analyzed separately.

Compared with children who never had distressing dreams, children who had persistent distressing dreams were 76% more likely to develop cognitive impairment by age 50 years (aOR, 1.76; 95% CI, 1.03-2.99; P = .037), and were about seven times more likely to be diagnosed with PD by age 50 years (aOR, 7.35; 95% CI, 1.03-52.73; P = .047).

The linear association was statistically significant for PD (P = .050) and had a trend toward statistical significance for cognitive impairment (P = .074).

Mechanism unclear

“Early-life nightmares might be causally associated with cognitive impairment and PD, noncausally associated with cognitive impairment and PD, or both. At this stage it remains unclear which of the three options is correct. Therefore, further research on mechanisms is needed,” Dr. Otaiku told this news organization.

“One plausible noncausal explanation is that there are shared genetic factors which predispose individuals to having frequent nightmares in childhood, and to developing neurodegenerative diseases such as AD or PD in adulthood,” he added.

It’s also plausible that having regular nightmares throughout childhood could be a causal risk factor for cognitive impairment and PD by causing chronic sleep disruption, he noted.

“Chronic sleep disruption due to nightmares might lead to impaired glymphatic clearance during sleep – and thus greater accumulation of pathological proteins in the brain, such as amyloid-beta and alpha-synuclein,” Dr. Otaiku said.

Disrupted sleep throughout childhood might also impair normal brain development, which could make children’s brains less resilient to neuropathologic damage, he said.

Clinical implications?

There are established treatments for childhood nightmares, including nonpharmacologic approaches.

“For children who have regular nightmares that lead to impaired daytime functioning, it may well be a good idea for them to see a sleep physician to discuss whether treatment may be needed,” Dr. Otaiku said.

But should doctors treat children with persistent nightmares for the purpose of preventing neurodegenerative diseases in adulthood or psychiatric problems in adolescence?

“It’s an interesting possibility. However, more research is needed to confirm these epidemiological associations and to determine whether or not nightmares are a causal risk factor for these conditions,” Dr. Otaiku concluded.

The study received no external funding. Dr. Otaiku reports no relevant disclosures.

A version of this article first appeared on Medscape.com.

Adverse childhood experiences (ACEs) are associated with increased motor and nonmotor symptoms of Parkinson’s disease (PD) and reduced quality of life (QOL), new research shows.

Results of the first study to evaluate the relationship between childhood trauma and PD investigators found that the relationship appears to be dose dependent. Patients with PD who reported more than one ACE all experienced a statistically significant decrease in QOL, and for each additional ACE, there was significant worsening of motor symptoms.

This study supports a recent-call to-action paper in JAMA Neurology encouraging adoption of “trauma-informed neurology,” study investigator Indu Subramanian, MD, clinical professor, department of neurology, University of California, Los Angeles, said in an interview.

“We need to start asking about ACEs in everyone. It should be part of our medical intake,” said Dr. Subramanian, who is also the director of the Southwest Parkinson’s Disease Research, Education, and Clinical Center, West Los Angeles Veterans Affairs Medical Center.

The study was published online in Neurology: Clinical Practice.
 

Hard on the mind and body

A robust body of literature has clearly established a connection between ACEs, which include physical and emotional abuse, neglect, and household dysfunction, and negative physical health outcomes across the lifespan. These include stroke, dementia, diabetes, cancer, cardiovascular disease, autoimmune disorders, hypertension, and premature death as well as psychosocial health outcomes such as anxiety, depression, substance use, and suicide.

However, until now, the effects of childhood trauma have not been evaluated in a PD population.

As part of the MVP study, 712 adults with PD responded to an online survey asking about childhood trauma.

As anticipated, patients with the least reported childhood trauma reported the highest current QOL and lowest patient-reported motor and nonmotor symptom burden compared with peers with higher reported childhood trauma, the researchers reported.

PD symptom burden increased and QOL decreased as the number of ACEs increased.

Patients with ACE scores of 4 or higher reported greater PD symptom severity for 45% of the variables assessed, including apathy, muscle pain, daytime sleepiness, restless leg syndrome, depression, fatigue, comprehension, and anxiety (P < .05), compared with peers with trauma scores of 0.

Limitations of the study included the cross-sectional nature, which prevents making any causal determinations. Also, the ACE questionnaire, because it is self-reported and a retrospective collection of data, introduces the risk for recall bias. In addition, 65% of respondents were women, and racial and ethnic minority groups were not well represented.

Looking ahead, Dr. Subramanian and coauthors believe future research should “attempt to include more diverse populations, attempt improve the response rate of these sensitive questions and, most importantly, determine whether the adverse outcomes associated with childhood trauma can be mitigated with lifestyle modification, psychosocial support, and intervention in adulthood.”

“As a trauma-informed approach, something sorely lacking yet needed in the field of movement disorders, clinicians can proactively screen for ACEs while being mindful to avoid retraumatization,” they suggested. “They can begin to identify how ACEs may physiologically contribute to PD symptom and focus on targeting appropriate interventions that may improve outcomes.”
 

Life experiences matter

In a comment, Michael S. Okun, MD, medical advisor, Parkinson’s Foundation, and director of the Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, said that “the idea that childhood trauma could be associated with a mild increase in severity of Parkinson’s symptoms such as apathy, pain, sleepiness and depression is fascinating.”

“We should however temper our enthusiasm for the results of this study because they were obtained through a direct patient survey, and not collected from large well characterized medical database,” Dr. Okun said.

He added” “If the data on childhood trauma and Parkinson’s can be replicated, we must ask why this could be?

“For Parkinson clinicians this as a reminder of how important obtaining a complete life history can be when strategizing on a plan to reduce motor and nonmotor Parkinson symptoms. Life experiences matter and can impact symptoms,” Dr. Okun said.

The MVP study was initiated with support of the National Center for Complementary and Integrative Health. The ongoing data collection has been supported by a donation from Sondra and Bill Fondren. Dr. Subramanian and Dr. Okun disclosed no potential conflicts of interest.

A version of this article first appeared on Medscape.com.

Adverse childhood experiences (ACEs) are associated with increased motor and nonmotor symptoms of Parkinson’s disease (PD) and reduced quality of life (QOL), new research shows.

Results of the first study to evaluate the relationship between childhood trauma and PD investigators found that the relationship appears to be dose dependent. Patients with PD who reported more than one ACE all experienced a statistically significant decrease in QOL, and for each additional ACE, there was significant worsening of motor symptoms.

This study supports a recent-call to-action paper in JAMA Neurology encouraging adoption of “trauma-informed neurology,” study investigator Indu Subramanian, MD, clinical professor, department of neurology, University of California, Los Angeles, said in an interview.

“We need to start asking about ACEs in everyone. It should be part of our medical intake,” said Dr. Subramanian, who is also the director of the Southwest Parkinson’s Disease Research, Education, and Clinical Center, West Los Angeles Veterans Affairs Medical Center.

The study was published online in Neurology: Clinical Practice.
 

Hard on the mind and body

A robust body of literature has clearly established a connection between ACEs, which include physical and emotional abuse, neglect, and household dysfunction, and negative physical health outcomes across the lifespan. These include stroke, dementia, diabetes, cancer, cardiovascular disease, autoimmune disorders, hypertension, and premature death as well as psychosocial health outcomes such as anxiety, depression, substance use, and suicide.

However, until now, the effects of childhood trauma have not been evaluated in a PD population.

As part of the MVP study, 712 adults with PD responded to an online survey asking about childhood trauma.

As anticipated, patients with the least reported childhood trauma reported the highest current QOL and lowest patient-reported motor and nonmotor symptom burden compared with peers with higher reported childhood trauma, the researchers reported.

PD symptom burden increased and QOL decreased as the number of ACEs increased.

Patients with ACE scores of 4 or higher reported greater PD symptom severity for 45% of the variables assessed, including apathy, muscle pain, daytime sleepiness, restless leg syndrome, depression, fatigue, comprehension, and anxiety (P < .05), compared with peers with trauma scores of 0.

Limitations of the study included the cross-sectional nature, which prevents making any causal determinations. Also, the ACE questionnaire, because it is self-reported and a retrospective collection of data, introduces the risk for recall bias. In addition, 65% of respondents were women, and racial and ethnic minority groups were not well represented.

Looking ahead, Dr. Subramanian and coauthors believe future research should “attempt to include more diverse populations, attempt improve the response rate of these sensitive questions and, most importantly, determine whether the adverse outcomes associated with childhood trauma can be mitigated with lifestyle modification, psychosocial support, and intervention in adulthood.”

“As a trauma-informed approach, something sorely lacking yet needed in the field of movement disorders, clinicians can proactively screen for ACEs while being mindful to avoid retraumatization,” they suggested. “They can begin to identify how ACEs may physiologically contribute to PD symptom and focus on targeting appropriate interventions that may improve outcomes.”
 

Life experiences matter

In a comment, Michael S. Okun, MD, medical advisor, Parkinson’s Foundation, and director of the Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, said that “the idea that childhood trauma could be associated with a mild increase in severity of Parkinson’s symptoms such as apathy, pain, sleepiness and depression is fascinating.”

“We should however temper our enthusiasm for the results of this study because they were obtained through a direct patient survey, and not collected from large well characterized medical database,” Dr. Okun said.

He added” “If the data on childhood trauma and Parkinson’s can be replicated, we must ask why this could be?

“For Parkinson clinicians this as a reminder of how important obtaining a complete life history can be when strategizing on a plan to reduce motor and nonmotor Parkinson symptoms. Life experiences matter and can impact symptoms,” Dr. Okun said.

The MVP study was initiated with support of the National Center for Complementary and Integrative Health. The ongoing data collection has been supported by a donation from Sondra and Bill Fondren. Dr. Subramanian and Dr. Okun disclosed no potential conflicts of interest.

A version of this article first appeared on Medscape.com.

Adverse childhood experiences (ACEs) are associated with increased motor and nonmotor symptoms of Parkinson’s disease (PD) and reduced quality of life (QOL), new research shows.

Results of the first study to evaluate the relationship between childhood trauma and PD investigators found that the relationship appears to be dose dependent. Patients with PD who reported more than one ACE all experienced a statistically significant decrease in QOL, and for each additional ACE, there was significant worsening of motor symptoms.

This study supports a recent-call to-action paper in JAMA Neurology encouraging adoption of “trauma-informed neurology,” study investigator Indu Subramanian, MD, clinical professor, department of neurology, University of California, Los Angeles, said in an interview.

“We need to start asking about ACEs in everyone. It should be part of our medical intake,” said Dr. Subramanian, who is also the director of the Southwest Parkinson’s Disease Research, Education, and Clinical Center, West Los Angeles Veterans Affairs Medical Center.

The study was published online in Neurology: Clinical Practice.
 

Hard on the mind and body

A robust body of literature has clearly established a connection between ACEs, which include physical and emotional abuse, neglect, and household dysfunction, and negative physical health outcomes across the lifespan. These include stroke, dementia, diabetes, cancer, cardiovascular disease, autoimmune disorders, hypertension, and premature death as well as psychosocial health outcomes such as anxiety, depression, substance use, and suicide.

However, until now, the effects of childhood trauma have not been evaluated in a PD population.

As part of the MVP study, 712 adults with PD responded to an online survey asking about childhood trauma.

As anticipated, patients with the least reported childhood trauma reported the highest current QOL and lowest patient-reported motor and nonmotor symptom burden compared with peers with higher reported childhood trauma, the researchers reported.

PD symptom burden increased and QOL decreased as the number of ACEs increased.

Patients with ACE scores of 4 or higher reported greater PD symptom severity for 45% of the variables assessed, including apathy, muscle pain, daytime sleepiness, restless leg syndrome, depression, fatigue, comprehension, and anxiety (P < .05), compared with peers with trauma scores of 0.

Limitations of the study included the cross-sectional nature, which prevents making any causal determinations. Also, the ACE questionnaire, because it is self-reported and a retrospective collection of data, introduces the risk for recall bias. In addition, 65% of respondents were women, and racial and ethnic minority groups were not well represented.

Looking ahead, Dr. Subramanian and coauthors believe future research should “attempt to include more diverse populations, attempt improve the response rate of these sensitive questions and, most importantly, determine whether the adverse outcomes associated with childhood trauma can be mitigated with lifestyle modification, psychosocial support, and intervention in adulthood.”

“As a trauma-informed approach, something sorely lacking yet needed in the field of movement disorders, clinicians can proactively screen for ACEs while being mindful to avoid retraumatization,” they suggested. “They can begin to identify how ACEs may physiologically contribute to PD symptom and focus on targeting appropriate interventions that may improve outcomes.”
 

Life experiences matter

In a comment, Michael S. Okun, MD, medical advisor, Parkinson’s Foundation, and director of the Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, said that “the idea that childhood trauma could be associated with a mild increase in severity of Parkinson’s symptoms such as apathy, pain, sleepiness and depression is fascinating.”

“We should however temper our enthusiasm for the results of this study because they were obtained through a direct patient survey, and not collected from large well characterized medical database,” Dr. Okun said.

He added” “If the data on childhood trauma and Parkinson’s can be replicated, we must ask why this could be?

“For Parkinson clinicians this as a reminder of how important obtaining a complete life history can be when strategizing on a plan to reduce motor and nonmotor Parkinson symptoms. Life experiences matter and can impact symptoms,” Dr. Okun said.

The MVP study was initiated with support of the National Center for Complementary and Integrative Health. The ongoing data collection has been supported by a donation from Sondra and Bill Fondren. Dr. Subramanian and Dr. Okun disclosed no potential conflicts of interest.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Dear colleagues, I am Christoph Diener from the medical faculty of the University of Duisburg-Essen in Germany. Today, I would like to discuss what happened in neurology in the past month.
 

Treatment of tension-type headache

I would like to start with headache. You are all aware that we have several new studies regarding the prevention of migraine, but very few studies involving nondrug treatments for tension-type headache.

A working group in Göttingen, Germany, conducted a study in people with frequent episodic and chronic tension-type headache. The first of the four randomized groups received traditional Chinese acupuncture for 3 months. The second group received physical therapy and exercise for 1 hour per week for 12 weeks. The third group received a combination of acupuncture and exercise. The last was a control group that received only standard care.

The outcome parameters of tension-type headache were evaluated after 6 months and again after 12 months. Previously, these same researchers published that the intensity but not the frequency of tension-type headache was reduced by active therapy.

In Cephalalgia, they published the outcome for the endpoints of depression, anxiety, and quality of life. Acupuncture, exercise, and the combination of the two improved depression, anxiety, and quality of life. This shows that nonmedical treatment is effective in people with frequent episodic and chronic tension-type headache.
 

Headache after COVID-19

The next study was published in Headache and discusses headache after COVID-19. In this review of published studies, more than 50% of people with COVID-19 develop headache. It is more frequent in young patients and people with preexisting primary headaches, such as migraine and tension-type headache. Prognosis is usually good, but some patients develop new, daily persistent headache, which is a major problem because treatment is unclear. We desperately need studies investigating how to treat this new, daily persistent headache after COVID-19.

SSRIs during COVID-19 infection

The next study also focuses on COVID-19. We have conflicting results from several studies suggesting that selective serotonin reuptake inhibitors might be effective in people with mild COVID-19 infection. This hypothesis was tested in a study in Brazil and was published in JAMA, The study included 1,288 outpatients with mild COVID-19 who either received 50 mg of fluvoxamine twice daily for 10 days or placebo. There was no benefit of the treatment for any outcome.

Preventing dementia with antihypertensive treatment

The next study was published in the European Heart Journal and addresses the question of whether effective antihypertensive treatment in elderly persons can prevent dementia. This is a meta-analysis of five placebo-controlled trials with more than 28,000 patients. The meta-analysis clearly shows that treating hypertension in elderly patients does prevent dementia. The benefit is higher if the blood pressure is lowered by a larger amount which also stays true for elderly patients. There is no negative impact of lowering blood pressure in this population.

Antiplatelet therapy

The next study was published in Stroke and reexamines whether resumption of antiplatelet therapy should be early or late in people who had an intracerebral hemorrhage while on antiplatelet therapy. In the Taiwanese Health Registry, this was studied in 1,584 patients. The researchers divided participants into groups based on whether antiplatelet therapy was resumed within 30 days or after 30 days. In 1 year, the rate of recurrent intracerebral hemorrhage was 3.2%. There was no difference whether antiplatelet therapy was resumed early or late.

Regular exercise in Parkinson’s disease

The final study is a review of nonmedical therapy. This meta-analysis of 19 randomized trials looked at the benefit of regular exercise in patients with Parkinson’s disease and depression. The analysis clearly showed that rigorous and moderate exercise improved depression in patients with Parkinson’s disease. This is very important because exercise improves not only the symptoms of Parkinson’s disease but also comorbid depression while presenting no serious adverse events or side effects.

Dr. Diener is a professor in the department of neurology at Stroke Center–Headache Center, University Duisburg-Essen, Germany. He disclosed ties with Abbott, Addex Pharma, Alder, Allergan, Almirall, Amgen, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Bristol-Myers Squibb, Boehringer Ingelheim, Chordate, CoAxia, Corimmun, Covidien, Coherex, CoLucid, Daiichi Sankyo, D-Pharm, Electrocore, Fresenius, GlaxoSmithKline, Grunenthal, Janssen-Cilag, Labrys Biologics Lilly, La Roche, Lundbeck, 3M Medica, MSD, Medtronic, Menarini, MindFrame, Minster, Neuroscore, Neurobiological Technologies, Novartis, Novo Nordisk, Johnson & Johnson, Knoll, Paion, Parke-Davis, Pierre Fabre, Pfizer Inc, Schaper and Brummer, Sanofi-Aventis, Schering-Plough, Servier, Solvay, St. Jude, Talecris, Thrombogenics, WebMD Global, Weber and Weber, Wyeth, and Yamanouchi. Dr. Diener has served as editor of Aktuelle Neurologie, Arzneimitteltherapie, Kopfschmerz News, Stroke News, and the Treatment Guidelines of the German Neurological Society; as co-editor of Cephalalgia; and on the editorial board of The Lancet Neurology, Stroke, European Neurology, and Cerebrovascular Disorders. The department of neurology in Essen is supported by the German Research Council, the German Ministry of Education and Research, European Union, National Institutes of Health, Bertelsmann Foundation, and Heinz Nixdorf Foundation. Dr. Diener has no ownership interest and does not own stocks in any pharmaceutical company. A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Dear colleagues, I am Christoph Diener from the medical faculty of the University of Duisburg-Essen in Germany. Today, I would like to discuss what happened in neurology in the past month.
 

Treatment of tension-type headache

I would like to start with headache. You are all aware that we have several new studies regarding the prevention of migraine, but very few studies involving nondrug treatments for tension-type headache.

A working group in Göttingen, Germany, conducted a study in people with frequent episodic and chronic tension-type headache. The first of the four randomized groups received traditional Chinese acupuncture for 3 months. The second group received physical therapy and exercise for 1 hour per week for 12 weeks. The third group received a combination of acupuncture and exercise. The last was a control group that received only standard care.

The outcome parameters of tension-type headache were evaluated after 6 months and again after 12 months. Previously, these same researchers published that the intensity but not the frequency of tension-type headache was reduced by active therapy.

In Cephalalgia, they published the outcome for the endpoints of depression, anxiety, and quality of life. Acupuncture, exercise, and the combination of the two improved depression, anxiety, and quality of life. This shows that nonmedical treatment is effective in people with frequent episodic and chronic tension-type headache.
 

Headache after COVID-19

The next study was published in Headache and discusses headache after COVID-19. In this review of published studies, more than 50% of people with COVID-19 develop headache. It is more frequent in young patients and people with preexisting primary headaches, such as migraine and tension-type headache. Prognosis is usually good, but some patients develop new, daily persistent headache, which is a major problem because treatment is unclear. We desperately need studies investigating how to treat this new, daily persistent headache after COVID-19.

SSRIs during COVID-19 infection

The next study also focuses on COVID-19. We have conflicting results from several studies suggesting that selective serotonin reuptake inhibitors might be effective in people with mild COVID-19 infection. This hypothesis was tested in a study in Brazil and was published in JAMA, The study included 1,288 outpatients with mild COVID-19 who either received 50 mg of fluvoxamine twice daily for 10 days or placebo. There was no benefit of the treatment for any outcome.

Preventing dementia with antihypertensive treatment

The next study was published in the European Heart Journal and addresses the question of whether effective antihypertensive treatment in elderly persons can prevent dementia. This is a meta-analysis of five placebo-controlled trials with more than 28,000 patients. The meta-analysis clearly shows that treating hypertension in elderly patients does prevent dementia. The benefit is higher if the blood pressure is lowered by a larger amount which also stays true for elderly patients. There is no negative impact of lowering blood pressure in this population.

Antiplatelet therapy

The next study was published in Stroke and reexamines whether resumption of antiplatelet therapy should be early or late in people who had an intracerebral hemorrhage while on antiplatelet therapy. In the Taiwanese Health Registry, this was studied in 1,584 patients. The researchers divided participants into groups based on whether antiplatelet therapy was resumed within 30 days or after 30 days. In 1 year, the rate of recurrent intracerebral hemorrhage was 3.2%. There was no difference whether antiplatelet therapy was resumed early or late.

Regular exercise in Parkinson’s disease

The final study is a review of nonmedical therapy. This meta-analysis of 19 randomized trials looked at the benefit of regular exercise in patients with Parkinson’s disease and depression. The analysis clearly showed that rigorous and moderate exercise improved depression in patients with Parkinson’s disease. This is very important because exercise improves not only the symptoms of Parkinson’s disease but also comorbid depression while presenting no serious adverse events or side effects.

Dr. Diener is a professor in the department of neurology at Stroke Center–Headache Center, University Duisburg-Essen, Germany. He disclosed ties with Abbott, Addex Pharma, Alder, Allergan, Almirall, Amgen, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Bristol-Myers Squibb, Boehringer Ingelheim, Chordate, CoAxia, Corimmun, Covidien, Coherex, CoLucid, Daiichi Sankyo, D-Pharm, Electrocore, Fresenius, GlaxoSmithKline, Grunenthal, Janssen-Cilag, Labrys Biologics Lilly, La Roche, Lundbeck, 3M Medica, MSD, Medtronic, Menarini, MindFrame, Minster, Neuroscore, Neurobiological Technologies, Novartis, Novo Nordisk, Johnson & Johnson, Knoll, Paion, Parke-Davis, Pierre Fabre, Pfizer Inc, Schaper and Brummer, Sanofi-Aventis, Schering-Plough, Servier, Solvay, St. Jude, Talecris, Thrombogenics, WebMD Global, Weber and Weber, Wyeth, and Yamanouchi. Dr. Diener has served as editor of Aktuelle Neurologie, Arzneimitteltherapie, Kopfschmerz News, Stroke News, and the Treatment Guidelines of the German Neurological Society; as co-editor of Cephalalgia; and on the editorial board of The Lancet Neurology, Stroke, European Neurology, and Cerebrovascular Disorders. The department of neurology in Essen is supported by the German Research Council, the German Ministry of Education and Research, European Union, National Institutes of Health, Bertelsmann Foundation, and Heinz Nixdorf Foundation. Dr. Diener has no ownership interest and does not own stocks in any pharmaceutical company. A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Dear colleagues, I am Christoph Diener from the medical faculty of the University of Duisburg-Essen in Germany. Today, I would like to discuss what happened in neurology in the past month.
 

Treatment of tension-type headache

I would like to start with headache. You are all aware that we have several new studies regarding the prevention of migraine, but very few studies involving nondrug treatments for tension-type headache.

A working group in Göttingen, Germany, conducted a study in people with frequent episodic and chronic tension-type headache. The first of the four randomized groups received traditional Chinese acupuncture for 3 months. The second group received physical therapy and exercise for 1 hour per week for 12 weeks. The third group received a combination of acupuncture and exercise. The last was a control group that received only standard care.

The outcome parameters of tension-type headache were evaluated after 6 months and again after 12 months. Previously, these same researchers published that the intensity but not the frequency of tension-type headache was reduced by active therapy.

In Cephalalgia, they published the outcome for the endpoints of depression, anxiety, and quality of life. Acupuncture, exercise, and the combination of the two improved depression, anxiety, and quality of life. This shows that nonmedical treatment is effective in people with frequent episodic and chronic tension-type headache.
 

Headache after COVID-19

The next study was published in Headache and discusses headache after COVID-19. In this review of published studies, more than 50% of people with COVID-19 develop headache. It is more frequent in young patients and people with preexisting primary headaches, such as migraine and tension-type headache. Prognosis is usually good, but some patients develop new, daily persistent headache, which is a major problem because treatment is unclear. We desperately need studies investigating how to treat this new, daily persistent headache after COVID-19.

SSRIs during COVID-19 infection

The next study also focuses on COVID-19. We have conflicting results from several studies suggesting that selective serotonin reuptake inhibitors might be effective in people with mild COVID-19 infection. This hypothesis was tested in a study in Brazil and was published in JAMA, The study included 1,288 outpatients with mild COVID-19 who either received 50 mg of fluvoxamine twice daily for 10 days or placebo. There was no benefit of the treatment for any outcome.

Preventing dementia with antihypertensive treatment

The next study was published in the European Heart Journal and addresses the question of whether effective antihypertensive treatment in elderly persons can prevent dementia. This is a meta-analysis of five placebo-controlled trials with more than 28,000 patients. The meta-analysis clearly shows that treating hypertension in elderly patients does prevent dementia. The benefit is higher if the blood pressure is lowered by a larger amount which also stays true for elderly patients. There is no negative impact of lowering blood pressure in this population.

Antiplatelet therapy

The next study was published in Stroke and reexamines whether resumption of antiplatelet therapy should be early or late in people who had an intracerebral hemorrhage while on antiplatelet therapy. In the Taiwanese Health Registry, this was studied in 1,584 patients. The researchers divided participants into groups based on whether antiplatelet therapy was resumed within 30 days or after 30 days. In 1 year, the rate of recurrent intracerebral hemorrhage was 3.2%. There was no difference whether antiplatelet therapy was resumed early or late.

Regular exercise in Parkinson’s disease

The final study is a review of nonmedical therapy. This meta-analysis of 19 randomized trials looked at the benefit of regular exercise in patients with Parkinson’s disease and depression. The analysis clearly showed that rigorous and moderate exercise improved depression in patients with Parkinson’s disease. This is very important because exercise improves not only the symptoms of Parkinson’s disease but also comorbid depression while presenting no serious adverse events or side effects.

Dr. Diener is a professor in the department of neurology at Stroke Center–Headache Center, University Duisburg-Essen, Germany. He disclosed ties with Abbott, Addex Pharma, Alder, Allergan, Almirall, Amgen, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Bristol-Myers Squibb, Boehringer Ingelheim, Chordate, CoAxia, Corimmun, Covidien, Coherex, CoLucid, Daiichi Sankyo, D-Pharm, Electrocore, Fresenius, GlaxoSmithKline, Grunenthal, Janssen-Cilag, Labrys Biologics Lilly, La Roche, Lundbeck, 3M Medica, MSD, Medtronic, Menarini, MindFrame, Minster, Neuroscore, Neurobiological Technologies, Novartis, Novo Nordisk, Johnson & Johnson, Knoll, Paion, Parke-Davis, Pierre Fabre, Pfizer Inc, Schaper and Brummer, Sanofi-Aventis, Schering-Plough, Servier, Solvay, St. Jude, Talecris, Thrombogenics, WebMD Global, Weber and Weber, Wyeth, and Yamanouchi. Dr. Diener has served as editor of Aktuelle Neurologie, Arzneimitteltherapie, Kopfschmerz News, Stroke News, and the Treatment Guidelines of the German Neurological Society; as co-editor of Cephalalgia; and on the editorial board of The Lancet Neurology, Stroke, European Neurology, and Cerebrovascular Disorders. The department of neurology in Essen is supported by the German Research Council, the German Ministry of Education and Research, European Union, National Institutes of Health, Bertelsmann Foundation, and Heinz Nixdorf Foundation. Dr. Diener has no ownership interest and does not own stocks in any pharmaceutical company. A version of this article originally appeared on Medscape.com.

A new “smart patch” composed of microneedles that can detect proinflammatory markers via simulated skin interstitial fluid (ISF) may help diagnose neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease very early on.

Originally developed to deliver medications and vaccines via the skin in a minimally invasive manner, the microneedle arrays were fitted with molecular sensors that, when placed on the skin, detect neuroinflammatory biomarkers such as interleukin-6 in as little as 6 minutes.

The literature suggests that these biomarkers of neurodegenerative disease are present years before patients become symptomatic, said study investigator Sanjiv Sharma, PhD.

“Neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease are [characterized by] progressive loss in nerve cell and brain cells, which leads to memory problems and a loss of mental ability. That is why early diagnosis is key to preventing the loss of brain tissue in dementia, which can go undetected for years,” added Dr. Sharma, who is a lecturer in medical engineering at Swansea (Wales) University.

Dr. Sharma developed the patch with scientists at the Polytechnic of Porto (Portugal) School of Engineering in Portugal. In 2022, they designed, and are currently testing, a microneedle patch that will deliver the COVID vaccine.

The investigators describe their research on the patch’s ability to detect IL-6 in an article published in ACS Omega.
 

At-home diagnosis?

“The skin is the largest organ in the body – it contains more skin interstitial fluid than the total blood volume,” Dr. Sharma noted. “This fluid is an ultrafiltrate of blood and holds biomarkers that complement other biofluids, such as sweat, saliva, and urine. It can be sampled in a minimally invasive manner and used either for point-of-care testing or real-time using microneedle devices.”

Dr. Sharma and associates tested the microneedle patch in artificial ISF that contained the inflammatory cytokine IL-6. They found that the patch accurately detected IL-6 concentrations as low as 1 pg/mL in the fabricated ISF solution.

“In general, the transdermal sensor presented here showed simplicity in designing, short measuring time, high accuracy, and low detection limit. This approach seems a successful tool for the screening of inflammatory biomarkers in point of care testing wherein the skin acts as a window to the body,” the investigators reported.

Dr. Sharma noted that early detection of neurodegenerative diseases is crucial, as once symptoms appear, the disease may have already progressed significantly, and meaningful intervention is challenging.

The device has yet to be tested in humans, which is the next step, said Dr. Sharma.

“We will have to test the hypothesis through extensive preclinical and clinical studies to determine if bloodless, transdermal (skin) diagnostics can offer a cost-effective device that could allow testing in simpler settings such as a clinician’s practice or even home settings,” he noted.
 

Early days

Commenting on the research, David K. Simon, MD, PhD, professor of neurology at Harvard Medical School, Boston, said it is “a promising step regarding validation of a potentially beneficial method for rapidly and accurately measuring IL-6.”

However, he added, “many additional steps are needed to validate the method in actual human skin and to determine whether or not measuring these biomarkers in skin will be useful in studies of neurodegenerative diseases.”

He noted that one study limitation is that inflammatory cytokines such as IL-6 are highly nonspecific, and levels are elevated in various diseases associated with inflammation.

“It is highly unlikely that measuring IL-6 will be useful as a diagnostic tool. However, it does have potential as a biomarker for measuring the impact of treatments aimed at reducing inflammation. As the authors point out, it’s more likely that clinicians will require a panel of biomarkers rather than only measuring IL-6,” he said.

The study was funded by Fundação para a Ciência e Tecnologia. The investigators disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new “smart patch” composed of microneedles that can detect proinflammatory markers via simulated skin interstitial fluid (ISF) may help diagnose neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease very early on.

Originally developed to deliver medications and vaccines via the skin in a minimally invasive manner, the microneedle arrays were fitted with molecular sensors that, when placed on the skin, detect neuroinflammatory biomarkers such as interleukin-6 in as little as 6 minutes.

The literature suggests that these biomarkers of neurodegenerative disease are present years before patients become symptomatic, said study investigator Sanjiv Sharma, PhD.

“Neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease are [characterized by] progressive loss in nerve cell and brain cells, which leads to memory problems and a loss of mental ability. That is why early diagnosis is key to preventing the loss of brain tissue in dementia, which can go undetected for years,” added Dr. Sharma, who is a lecturer in medical engineering at Swansea (Wales) University.

Dr. Sharma developed the patch with scientists at the Polytechnic of Porto (Portugal) School of Engineering in Portugal. In 2022, they designed, and are currently testing, a microneedle patch that will deliver the COVID vaccine.

The investigators describe their research on the patch’s ability to detect IL-6 in an article published in ACS Omega.
 

At-home diagnosis?

“The skin is the largest organ in the body – it contains more skin interstitial fluid than the total blood volume,” Dr. Sharma noted. “This fluid is an ultrafiltrate of blood and holds biomarkers that complement other biofluids, such as sweat, saliva, and urine. It can be sampled in a minimally invasive manner and used either for point-of-care testing or real-time using microneedle devices.”

Dr. Sharma and associates tested the microneedle patch in artificial ISF that contained the inflammatory cytokine IL-6. They found that the patch accurately detected IL-6 concentrations as low as 1 pg/mL in the fabricated ISF solution.

“In general, the transdermal sensor presented here showed simplicity in designing, short measuring time, high accuracy, and low detection limit. This approach seems a successful tool for the screening of inflammatory biomarkers in point of care testing wherein the skin acts as a window to the body,” the investigators reported.

Dr. Sharma noted that early detection of neurodegenerative diseases is crucial, as once symptoms appear, the disease may have already progressed significantly, and meaningful intervention is challenging.

The device has yet to be tested in humans, which is the next step, said Dr. Sharma.

“We will have to test the hypothesis through extensive preclinical and clinical studies to determine if bloodless, transdermal (skin) diagnostics can offer a cost-effective device that could allow testing in simpler settings such as a clinician’s practice or even home settings,” he noted.
 

Early days

Commenting on the research, David K. Simon, MD, PhD, professor of neurology at Harvard Medical School, Boston, said it is “a promising step regarding validation of a potentially beneficial method for rapidly and accurately measuring IL-6.”

However, he added, “many additional steps are needed to validate the method in actual human skin and to determine whether or not measuring these biomarkers in skin will be useful in studies of neurodegenerative diseases.”

He noted that one study limitation is that inflammatory cytokines such as IL-6 are highly nonspecific, and levels are elevated in various diseases associated with inflammation.

“It is highly unlikely that measuring IL-6 will be useful as a diagnostic tool. However, it does have potential as a biomarker for measuring the impact of treatments aimed at reducing inflammation. As the authors point out, it’s more likely that clinicians will require a panel of biomarkers rather than only measuring IL-6,” he said.

The study was funded by Fundação para a Ciência e Tecnologia. The investigators disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new “smart patch” composed of microneedles that can detect proinflammatory markers via simulated skin interstitial fluid (ISF) may help diagnose neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease very early on.

Originally developed to deliver medications and vaccines via the skin in a minimally invasive manner, the microneedle arrays were fitted with molecular sensors that, when placed on the skin, detect neuroinflammatory biomarkers such as interleukin-6 in as little as 6 minutes.

The literature suggests that these biomarkers of neurodegenerative disease are present years before patients become symptomatic, said study investigator Sanjiv Sharma, PhD.

“Neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease are [characterized by] progressive loss in nerve cell and brain cells, which leads to memory problems and a loss of mental ability. That is why early diagnosis is key to preventing the loss of brain tissue in dementia, which can go undetected for years,” added Dr. Sharma, who is a lecturer in medical engineering at Swansea (Wales) University.

Dr. Sharma developed the patch with scientists at the Polytechnic of Porto (Portugal) School of Engineering in Portugal. In 2022, they designed, and are currently testing, a microneedle patch that will deliver the COVID vaccine.

The investigators describe their research on the patch’s ability to detect IL-6 in an article published in ACS Omega.
 

At-home diagnosis?

“The skin is the largest organ in the body – it contains more skin interstitial fluid than the total blood volume,” Dr. Sharma noted. “This fluid is an ultrafiltrate of blood and holds biomarkers that complement other biofluids, such as sweat, saliva, and urine. It can be sampled in a minimally invasive manner and used either for point-of-care testing or real-time using microneedle devices.”

Dr. Sharma and associates tested the microneedle patch in artificial ISF that contained the inflammatory cytokine IL-6. They found that the patch accurately detected IL-6 concentrations as low as 1 pg/mL in the fabricated ISF solution.

“In general, the transdermal sensor presented here showed simplicity in designing, short measuring time, high accuracy, and low detection limit. This approach seems a successful tool for the screening of inflammatory biomarkers in point of care testing wherein the skin acts as a window to the body,” the investigators reported.

Dr. Sharma noted that early detection of neurodegenerative diseases is crucial, as once symptoms appear, the disease may have already progressed significantly, and meaningful intervention is challenging.

The device has yet to be tested in humans, which is the next step, said Dr. Sharma.

“We will have to test the hypothesis through extensive preclinical and clinical studies to determine if bloodless, transdermal (skin) diagnostics can offer a cost-effective device that could allow testing in simpler settings such as a clinician’s practice or even home settings,” he noted.
 

Early days

Commenting on the research, David K. Simon, MD, PhD, professor of neurology at Harvard Medical School, Boston, said it is “a promising step regarding validation of a potentially beneficial method for rapidly and accurately measuring IL-6.”

However, he added, “many additional steps are needed to validate the method in actual human skin and to determine whether or not measuring these biomarkers in skin will be useful in studies of neurodegenerative diseases.”

He noted that one study limitation is that inflammatory cytokines such as IL-6 are highly nonspecific, and levels are elevated in various diseases associated with inflammation.

“It is highly unlikely that measuring IL-6 will be useful as a diagnostic tool. However, it does have potential as a biomarker for measuring the impact of treatments aimed at reducing inflammation. As the authors point out, it’s more likely that clinicians will require a panel of biomarkers rather than only measuring IL-6,” he said.

The study was funded by Fundação para a Ciência e Tecnologia. The investigators disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Hidden in the Dec. 1, 2022, issue of the New England Journal of Medicine was a small article on using deferiprone for Parkinson’s disease.

The idea behind it makes sense. A key factor in Parkinson’s disease is a loss of cells in the substantia nigra. The cells that have been lost have a build-up of iron content, suggesting that iron contributes to their demise. Therefore, maybe using an iron chelating agent to remove it may help.

Like I said, it makes sense.

Unfortunately, it didn’t quite work that way. In spite of a clear reduction of nigrostriatal iron, compared with the placebo group, the treated patients had worse MDS-UPDRS scores over 36 weeks than those on the placebo.

Back to the drawing board.

I’m not criticizing the people who did the study – it seemed like a reasonable hypothesis, and testing it is the only way we find out if it’s correct. We learn just as much, if not more, from a negative study as from a positive one, incrementally working toward the answer with each.

We face the same thing with the amyloid theory in Alzheimer’s disease. Getting rid of amyloid should fix the problem.

But it doesn’t, at least not completely. Even lecanemab, the latest-and-greatest of treatments, only shows a 27% slowing in disease progression. This is certainly meaningful – I’m not knocking it – but we’re still far from a cure. To date we haven’t even stopped disease progression, let alone reversed it.

Although the new drugs have a remarkable mechanism of action, the clinical results aren’t nearly as good as one would expect if amyloid was the whole issue.

Which, at this point, it probably isn’t, anymore than nigrostriatal iron deposition is the sole cause of Parkinson’s disease.

In medicine, as in so many other things, there’s simply a lot that we don’t know yet. Right now we’re better able to find planets 27,700 light years away (SWEEPS-11) than we are at knowing the cause of neuronal changes in the person sitting across the desk from us. That’s not saying we won’t have the answers someday, it just means we don’t have them now.

I was in my 3rd year of medical school in January of 1992, (surgery rotation at the Omaha VA, to be specific) when the first definitive planet outside our solar system was identified. Today, 31 years later, the number of exoplanets stands at 5,297.

But the laws of physics are generally a lot more predictable than those of biology.

That doesn’t mean we won’t find the answers, or more effective treatments, eventually. But it will take more time, work, and studies – with both positive and negative results – to get there.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Hidden in the Dec. 1, 2022, issue of the New England Journal of Medicine was a small article on using deferiprone for Parkinson’s disease.

The idea behind it makes sense. A key factor in Parkinson’s disease is a loss of cells in the substantia nigra. The cells that have been lost have a build-up of iron content, suggesting that iron contributes to their demise. Therefore, maybe using an iron chelating agent to remove it may help.

Like I said, it makes sense.

Unfortunately, it didn’t quite work that way. In spite of a clear reduction of nigrostriatal iron, compared with the placebo group, the treated patients had worse MDS-UPDRS scores over 36 weeks than those on the placebo.

Back to the drawing board.

I’m not criticizing the people who did the study – it seemed like a reasonable hypothesis, and testing it is the only way we find out if it’s correct. We learn just as much, if not more, from a negative study as from a positive one, incrementally working toward the answer with each.

We face the same thing with the amyloid theory in Alzheimer’s disease. Getting rid of amyloid should fix the problem.

But it doesn’t, at least not completely. Even lecanemab, the latest-and-greatest of treatments, only shows a 27% slowing in disease progression. This is certainly meaningful – I’m not knocking it – but we’re still far from a cure. To date we haven’t even stopped disease progression, let alone reversed it.

Although the new drugs have a remarkable mechanism of action, the clinical results aren’t nearly as good as one would expect if amyloid was the whole issue.

Which, at this point, it probably isn’t, anymore than nigrostriatal iron deposition is the sole cause of Parkinson’s disease.

In medicine, as in so many other things, there’s simply a lot that we don’t know yet. Right now we’re better able to find planets 27,700 light years away (SWEEPS-11) than we are at knowing the cause of neuronal changes in the person sitting across the desk from us. That’s not saying we won’t have the answers someday, it just means we don’t have them now.

I was in my 3rd year of medical school in January of 1992, (surgery rotation at the Omaha VA, to be specific) when the first definitive planet outside our solar system was identified. Today, 31 years later, the number of exoplanets stands at 5,297.

But the laws of physics are generally a lot more predictable than those of biology.

That doesn’t mean we won’t find the answers, or more effective treatments, eventually. But it will take more time, work, and studies – with both positive and negative results – to get there.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Hidden in the Dec. 1, 2022, issue of the New England Journal of Medicine was a small article on using deferiprone for Parkinson’s disease.

The idea behind it makes sense. A key factor in Parkinson’s disease is a loss of cells in the substantia nigra. The cells that have been lost have a build-up of iron content, suggesting that iron contributes to their demise. Therefore, maybe using an iron chelating agent to remove it may help.

Like I said, it makes sense.

Unfortunately, it didn’t quite work that way. In spite of a clear reduction of nigrostriatal iron, compared with the placebo group, the treated patients had worse MDS-UPDRS scores over 36 weeks than those on the placebo.

Back to the drawing board.

I’m not criticizing the people who did the study – it seemed like a reasonable hypothesis, and testing it is the only way we find out if it’s correct. We learn just as much, if not more, from a negative study as from a positive one, incrementally working toward the answer with each.

We face the same thing with the amyloid theory in Alzheimer’s disease. Getting rid of amyloid should fix the problem.

But it doesn’t, at least not completely. Even lecanemab, the latest-and-greatest of treatments, only shows a 27% slowing in disease progression. This is certainly meaningful – I’m not knocking it – but we’re still far from a cure. To date we haven’t even stopped disease progression, let alone reversed it.

Although the new drugs have a remarkable mechanism of action, the clinical results aren’t nearly as good as one would expect if amyloid was the whole issue.

Which, at this point, it probably isn’t, anymore than nigrostriatal iron deposition is the sole cause of Parkinson’s disease.

In medicine, as in so many other things, there’s simply a lot that we don’t know yet. Right now we’re better able to find planets 27,700 light years away (SWEEPS-11) than we are at knowing the cause of neuronal changes in the person sitting across the desk from us. That’s not saying we won’t have the answers someday, it just means we don’t have them now.

I was in my 3rd year of medical school in January of 1992, (surgery rotation at the Omaha VA, to be specific) when the first definitive planet outside our solar system was identified. Today, 31 years later, the number of exoplanets stands at 5,297.

But the laws of physics are generally a lot more predictable than those of biology.

That doesn’t mean we won’t find the answers, or more effective treatments, eventually. But it will take more time, work, and studies – with both positive and negative results – to get there.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

How many of you hadn’t heard of ambroxol until the last few weeks?

How many of you have gotten at least one call asking for a prescription for it in that time?

I’ll raise my hand on both accounts.

Ambroxol seems relatively innocuous – an over-the-counter cold medication commonly used on planet Earth (though not approved in the U.S. for whatever reason). But in the last few years some interesting data have cropped up that it may help with Parkinson’s disease.

“May” being the key word here.

Now, I’m not saying it will or won’t do something. The trials that are being started will show that. It would be totally awesome if it did.

But we’ve been here before: The hope that some old, inexpensive, and widely available medication would turn out to have an amazing benefit we didn’t anticipate. We saw this with hydroxychloroquine and ivermectin during the pandemic. Before that we saw all kinds of speculative ideas that statins would be effective for diseases from multiple sclerosis to Alzheimer’s disease.

And, as with many incurable diseases, patients and their families are hoping for a breakthrough. We have plenty of treatments for Parkinson’s disease, but no cures yet. So any potentially effective drug news makes the rounds quickly on news sites, patient advocacy sites, Facebook, and others.

Like the childrens’ telephone game, each time the story is repeated it changes a bit. We’ve gone from an article saying the drug is starting clinical trials to see if it works, to it being a cure now on the marketplace.

Which is when people start calling my office. Most are disappointed to learn that its benefit (if any) is unknown and that it’s not even available. A few get confrontational, accusing me of withholding treatment, when “everyone knows” the drug works.

Believe me, if I had a cure I’d be thrilled to be able to offer it.

I understand that patients and families want a cure.

I understand hope.

I want ambroxol to work for Parkinson’s disease and make a huge difference in the lives of those affected by it. Maybe it will. Or maybe it won’t.

But these things take time to figure out. None of the amazing medications and hi-tech toys we have came about overnight. They were all years in the making.

That’s how science works, and medicine is as much a science as an art.

The art is being able to explain this to patients, and still allow them to hope.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

How many of you hadn’t heard of ambroxol until the last few weeks?

How many of you have gotten at least one call asking for a prescription for it in that time?

I’ll raise my hand on both accounts.

Ambroxol seems relatively innocuous – an over-the-counter cold medication commonly used on planet Earth (though not approved in the U.S. for whatever reason). But in the last few years some interesting data have cropped up that it may help with Parkinson’s disease.

“May” being the key word here.

Now, I’m not saying it will or won’t do something. The trials that are being started will show that. It would be totally awesome if it did.

But we’ve been here before: The hope that some old, inexpensive, and widely available medication would turn out to have an amazing benefit we didn’t anticipate. We saw this with hydroxychloroquine and ivermectin during the pandemic. Before that we saw all kinds of speculative ideas that statins would be effective for diseases from multiple sclerosis to Alzheimer’s disease.

And, as with many incurable diseases, patients and their families are hoping for a breakthrough. We have plenty of treatments for Parkinson’s disease, but no cures yet. So any potentially effective drug news makes the rounds quickly on news sites, patient advocacy sites, Facebook, and others.

Like the childrens’ telephone game, each time the story is repeated it changes a bit. We’ve gone from an article saying the drug is starting clinical trials to see if it works, to it being a cure now on the marketplace.

Which is when people start calling my office. Most are disappointed to learn that its benefit (if any) is unknown and that it’s not even available. A few get confrontational, accusing me of withholding treatment, when “everyone knows” the drug works.

Believe me, if I had a cure I’d be thrilled to be able to offer it.

I understand that patients and families want a cure.

I understand hope.

I want ambroxol to work for Parkinson’s disease and make a huge difference in the lives of those affected by it. Maybe it will. Or maybe it won’t.

But these things take time to figure out. None of the amazing medications and hi-tech toys we have came about overnight. They were all years in the making.

That’s how science works, and medicine is as much a science as an art.

The art is being able to explain this to patients, and still allow them to hope.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

How many of you hadn’t heard of ambroxol until the last few weeks?

How many of you have gotten at least one call asking for a prescription for it in that time?

I’ll raise my hand on both accounts.

Ambroxol seems relatively innocuous – an over-the-counter cold medication commonly used on planet Earth (though not approved in the U.S. for whatever reason). But in the last few years some interesting data have cropped up that it may help with Parkinson’s disease.

“May” being the key word here.

Now, I’m not saying it will or won’t do something. The trials that are being started will show that. It would be totally awesome if it did.

But we’ve been here before: The hope that some old, inexpensive, and widely available medication would turn out to have an amazing benefit we didn’t anticipate. We saw this with hydroxychloroquine and ivermectin during the pandemic. Before that we saw all kinds of speculative ideas that statins would be effective for diseases from multiple sclerosis to Alzheimer’s disease.

And, as with many incurable diseases, patients and their families are hoping for a breakthrough. We have plenty of treatments for Parkinson’s disease, but no cures yet. So any potentially effective drug news makes the rounds quickly on news sites, patient advocacy sites, Facebook, and others.

Like the childrens’ telephone game, each time the story is repeated it changes a bit. We’ve gone from an article saying the drug is starting clinical trials to see if it works, to it being a cure now on the marketplace.

Which is when people start calling my office. Most are disappointed to learn that its benefit (if any) is unknown and that it’s not even available. A few get confrontational, accusing me of withholding treatment, when “everyone knows” the drug works.

Believe me, if I had a cure I’d be thrilled to be able to offer it.

I understand that patients and families want a cure.

I understand hope.

I want ambroxol to work for Parkinson’s disease and make a huge difference in the lives of those affected by it. Maybe it will. Or maybe it won’t.

But these things take time to figure out. None of the amazing medications and hi-tech toys we have came about overnight. They were all years in the making.

That’s how science works, and medicine is as much a science as an art.

The art is being able to explain this to patients, and still allow them to hope.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Antiepileptic drugs (AEDs) are linked to an increased risk of Parkinson’s disease, new research suggests.

Drawing on data from the UK Biobank, investigators compared more than 1,400 individuals diagnosed with Parkinson’s disease with matched control persons and found a considerably higher risk of developing Parkinson’s disease among those who had taken AEDs in comparison with those who had not. There was a trend linking a greater number of AED prescriptions and multiple AEDs associated with a greater risk for Parkinson’s disease.

“We observed an association between the most commonly prescribed antiepileptic drugs in the U.K. and Parkinson’s disease using data from UK Biobank,” said senior author Alastair Noyce, PhD, professor of neurology and neuroepidemiology and honorary consultant neurologist, Queen Mary University of London.

“This is the first time that a comprehensive study of the link between AEDs and Parkinson’s disease has been undertaken,” said Dr. Noyce.

He added that the findings have no immediate clinical implications, “but further research is definitely needed, [as] this is an interesting observation made in a research setting.”

The study was published online in JAMA Neurology.
 

Plausible, but unclear link

Recent observational studies have found a “temporal association” between epilepsy and incident Parkinson’s disease, but the mechanism underlying this association is “unclear,” the authors wrote.

It is “plausible” that AEDs “may account for some or all of the apparent association between epilepsy and Parkinson’s disease” and that movement disorders are potential side effects of AEDs, but the association between AEDs and Parkinson’s disease has “not been well studied,” so it remains “unclear” whether AEDs play a role in the association.

“We have previously reported an association between epilepsy and Parkinson’s disease in several different datasets. Here, we wanted to see if it could be explained by an association with the drugs used to treat epilepsy rather than epilepsy per se,” Dr. Noyce explained.
 

Are AEDs the culprit?

The researchers used data from the UK Biobank, a longitudinal cohort study with more than 500,000 participants, as well as linked primary care medication data to conduct a nested case-control study to investigate this potential association. Participants ranged in age from 40 to 69 years and were recruited between 2006 and 2010.

The researchers compared 1,433 individuals diagnosed with Parkinson’s disease with 8,598 control persons who were matched in a 6:1 ratio for age, sex, race, ethnicity, and socioeconomic status (median [interquartile range] age, 71 [65-75] years; 60.9% men; 97.5% White).

Of those with Parkinson’s disease, 4.3% had been prescribed an AED prior to the date of their being diagnosed with Parkinson’s disease, compared with 2.5% in the control group; 4.4% had been diagnosed with epilepsy, compared with 1% of the control persons.

The strongest evidence was for the association between lamotrigine, levetiracetam, and sodium valproate and Parkinson’s disease. There was “weaker evidence” for carbamazepine, although all the AEDs were associated with a higher risk of Parkinson’s disease.

Alternative explanations

Commenting on the research, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association, said, “It has been established in prior research that there is an association between epilepsy and Parkinson’s disease.” The current study “shows that having had a prescription written for one of four antiepileptic medications was associated with subsequently receiving a diagnosis of Parkinson’s disease.”

Although one possible conclusion is that the AEDs themselves increase the risk of developing Parkinson’s disease, “there seem to be other alternative explanations as to why a person who had been prescribed AEDs has an increased risk of receiving a diagnosis of Parkinson’s disease,” said Dr. Gilbert, an associate professor of neurology at Bellevue Hospital Center, New York, who was not involved with the current study.

For example, pre-motor changes in the brain of persons with Parkinson’s disease “may increase the risk of requiring an AED by potentially increasing the risk of having a seizure,” and “changes in the brain caused by the seizures for which AEDs are prescribed may increase the risk of Parkinson’s disease.”

Moreover, psychiatric changes related to Parkinson’s disease may have led to the prescription for AEDs, because at least two of the AEDs are also prescribed for mood stabilization, Dr. Gilbert suggested.

“An unanswered question that the paper acknowledges is, what about people who receive AEDs for reasons other than seizures? Do they also have an increased risk of Parkinson’s disease? This would be an interesting population to focus on because it would remove the link between AEDs and seizure and focus on the association between AEDs and Parkinson’s disease,” Dr. Gilbert said.

She emphasized that people who take AEDs for seizures “should not jump to the conclusion that they must come off these medications so as not to increase their risk of developing Parkinson’s disease.” She noted that having seizures “can be dangerous – injuries can occur during a seizure, and if a seizure can’t be stopped or a number occur in rapid succession, brain injury may result.”

For these reasons, people with “a tendency to have seizures need to protect themselves with AEDs” and “should certainly reach out to their neurologists with any questions,” Dr. Gilbert said.

The Preventive Neurology Unit is funded by Barts Charity. The Apocrita High Performance Cluster facility, supported by Queen Mary University London Research–IT Services, was used for this research. Dr. Noyce has received grants from Barts Charity, Parkinson’s UK, Cure Parkinson’s, the Michael J. Fox Foundation, Innovate UK, Solvemed, and Alchemab and personal fees from AstraZeneca, AbbVie, Zambon, BIAL, uMedeor, Alchemab, Britannia, and Charco Neurotech outside the submitted work. The other authors’ disclosures are listed on the original article. Dr. Gilbert reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Antiepileptic drugs (AEDs) are linked to an increased risk of Parkinson’s disease, new research suggests.

Drawing on data from the UK Biobank, investigators compared more than 1,400 individuals diagnosed with Parkinson’s disease with matched control persons and found a considerably higher risk of developing Parkinson’s disease among those who had taken AEDs in comparison with those who had not. There was a trend linking a greater number of AED prescriptions and multiple AEDs associated with a greater risk for Parkinson’s disease.

“We observed an association between the most commonly prescribed antiepileptic drugs in the U.K. and Parkinson’s disease using data from UK Biobank,” said senior author Alastair Noyce, PhD, professor of neurology and neuroepidemiology and honorary consultant neurologist, Queen Mary University of London.

“This is the first time that a comprehensive study of the link between AEDs and Parkinson’s disease has been undertaken,” said Dr. Noyce.

He added that the findings have no immediate clinical implications, “but further research is definitely needed, [as] this is an interesting observation made in a research setting.”

The study was published online in JAMA Neurology.
 

Plausible, but unclear link

Recent observational studies have found a “temporal association” between epilepsy and incident Parkinson’s disease, but the mechanism underlying this association is “unclear,” the authors wrote.

It is “plausible” that AEDs “may account for some or all of the apparent association between epilepsy and Parkinson’s disease” and that movement disorders are potential side effects of AEDs, but the association between AEDs and Parkinson’s disease has “not been well studied,” so it remains “unclear” whether AEDs play a role in the association.

“We have previously reported an association between epilepsy and Parkinson’s disease in several different datasets. Here, we wanted to see if it could be explained by an association with the drugs used to treat epilepsy rather than epilepsy per se,” Dr. Noyce explained.
 

Are AEDs the culprit?

The researchers used data from the UK Biobank, a longitudinal cohort study with more than 500,000 participants, as well as linked primary care medication data to conduct a nested case-control study to investigate this potential association. Participants ranged in age from 40 to 69 years and were recruited between 2006 and 2010.

The researchers compared 1,433 individuals diagnosed with Parkinson’s disease with 8,598 control persons who were matched in a 6:1 ratio for age, sex, race, ethnicity, and socioeconomic status (median [interquartile range] age, 71 [65-75] years; 60.9% men; 97.5% White).

Of those with Parkinson’s disease, 4.3% had been prescribed an AED prior to the date of their being diagnosed with Parkinson’s disease, compared with 2.5% in the control group; 4.4% had been diagnosed with epilepsy, compared with 1% of the control persons.

The strongest evidence was for the association between lamotrigine, levetiracetam, and sodium valproate and Parkinson’s disease. There was “weaker evidence” for carbamazepine, although all the AEDs were associated with a higher risk of Parkinson’s disease.

Alternative explanations

Commenting on the research, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association, said, “It has been established in prior research that there is an association between epilepsy and Parkinson’s disease.” The current study “shows that having had a prescription written for one of four antiepileptic medications was associated with subsequently receiving a diagnosis of Parkinson’s disease.”

Although one possible conclusion is that the AEDs themselves increase the risk of developing Parkinson’s disease, “there seem to be other alternative explanations as to why a person who had been prescribed AEDs has an increased risk of receiving a diagnosis of Parkinson’s disease,” said Dr. Gilbert, an associate professor of neurology at Bellevue Hospital Center, New York, who was not involved with the current study.

For example, pre-motor changes in the brain of persons with Parkinson’s disease “may increase the risk of requiring an AED by potentially increasing the risk of having a seizure,” and “changes in the brain caused by the seizures for which AEDs are prescribed may increase the risk of Parkinson’s disease.”

Moreover, psychiatric changes related to Parkinson’s disease may have led to the prescription for AEDs, because at least two of the AEDs are also prescribed for mood stabilization, Dr. Gilbert suggested.

“An unanswered question that the paper acknowledges is, what about people who receive AEDs for reasons other than seizures? Do they also have an increased risk of Parkinson’s disease? This would be an interesting population to focus on because it would remove the link between AEDs and seizure and focus on the association between AEDs and Parkinson’s disease,” Dr. Gilbert said.

She emphasized that people who take AEDs for seizures “should not jump to the conclusion that they must come off these medications so as not to increase their risk of developing Parkinson’s disease.” She noted that having seizures “can be dangerous – injuries can occur during a seizure, and if a seizure can’t be stopped or a number occur in rapid succession, brain injury may result.”

For these reasons, people with “a tendency to have seizures need to protect themselves with AEDs” and “should certainly reach out to their neurologists with any questions,” Dr. Gilbert said.

The Preventive Neurology Unit is funded by Barts Charity. The Apocrita High Performance Cluster facility, supported by Queen Mary University London Research–IT Services, was used for this research. Dr. Noyce has received grants from Barts Charity, Parkinson’s UK, Cure Parkinson’s, the Michael J. Fox Foundation, Innovate UK, Solvemed, and Alchemab and personal fees from AstraZeneca, AbbVie, Zambon, BIAL, uMedeor, Alchemab, Britannia, and Charco Neurotech outside the submitted work. The other authors’ disclosures are listed on the original article. Dr. Gilbert reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Antiepileptic drugs (AEDs) are linked to an increased risk of Parkinson’s disease, new research suggests.

Drawing on data from the UK Biobank, investigators compared more than 1,400 individuals diagnosed with Parkinson’s disease with matched control persons and found a considerably higher risk of developing Parkinson’s disease among those who had taken AEDs in comparison with those who had not. There was a trend linking a greater number of AED prescriptions and multiple AEDs associated with a greater risk for Parkinson’s disease.

“We observed an association between the most commonly prescribed antiepileptic drugs in the U.K. and Parkinson’s disease using data from UK Biobank,” said senior author Alastair Noyce, PhD, professor of neurology and neuroepidemiology and honorary consultant neurologist, Queen Mary University of London.

“This is the first time that a comprehensive study of the link between AEDs and Parkinson’s disease has been undertaken,” said Dr. Noyce.

He added that the findings have no immediate clinical implications, “but further research is definitely needed, [as] this is an interesting observation made in a research setting.”

The study was published online in JAMA Neurology.
 

Plausible, but unclear link

Recent observational studies have found a “temporal association” between epilepsy and incident Parkinson’s disease, but the mechanism underlying this association is “unclear,” the authors wrote.

It is “plausible” that AEDs “may account for some or all of the apparent association between epilepsy and Parkinson’s disease” and that movement disorders are potential side effects of AEDs, but the association between AEDs and Parkinson’s disease has “not been well studied,” so it remains “unclear” whether AEDs play a role in the association.

“We have previously reported an association between epilepsy and Parkinson’s disease in several different datasets. Here, we wanted to see if it could be explained by an association with the drugs used to treat epilepsy rather than epilepsy per se,” Dr. Noyce explained.
 

Are AEDs the culprit?

The researchers used data from the UK Biobank, a longitudinal cohort study with more than 500,000 participants, as well as linked primary care medication data to conduct a nested case-control study to investigate this potential association. Participants ranged in age from 40 to 69 years and were recruited between 2006 and 2010.

The researchers compared 1,433 individuals diagnosed with Parkinson’s disease with 8,598 control persons who were matched in a 6:1 ratio for age, sex, race, ethnicity, and socioeconomic status (median [interquartile range] age, 71 [65-75] years; 60.9% men; 97.5% White).

Of those with Parkinson’s disease, 4.3% had been prescribed an AED prior to the date of their being diagnosed with Parkinson’s disease, compared with 2.5% in the control group; 4.4% had been diagnosed with epilepsy, compared with 1% of the control persons.

The strongest evidence was for the association between lamotrigine, levetiracetam, and sodium valproate and Parkinson’s disease. There was “weaker evidence” for carbamazepine, although all the AEDs were associated with a higher risk of Parkinson’s disease.

Alternative explanations

Commenting on the research, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association, said, “It has been established in prior research that there is an association between epilepsy and Parkinson’s disease.” The current study “shows that having had a prescription written for one of four antiepileptic medications was associated with subsequently receiving a diagnosis of Parkinson’s disease.”

Although one possible conclusion is that the AEDs themselves increase the risk of developing Parkinson’s disease, “there seem to be other alternative explanations as to why a person who had been prescribed AEDs has an increased risk of receiving a diagnosis of Parkinson’s disease,” said Dr. Gilbert, an associate professor of neurology at Bellevue Hospital Center, New York, who was not involved with the current study.

For example, pre-motor changes in the brain of persons with Parkinson’s disease “may increase the risk of requiring an AED by potentially increasing the risk of having a seizure,” and “changes in the brain caused by the seizures for which AEDs are prescribed may increase the risk of Parkinson’s disease.”

Moreover, psychiatric changes related to Parkinson’s disease may have led to the prescription for AEDs, because at least two of the AEDs are also prescribed for mood stabilization, Dr. Gilbert suggested.

“An unanswered question that the paper acknowledges is, what about people who receive AEDs for reasons other than seizures? Do they also have an increased risk of Parkinson’s disease? This would be an interesting population to focus on because it would remove the link between AEDs and seizure and focus on the association between AEDs and Parkinson’s disease,” Dr. Gilbert said.

She emphasized that people who take AEDs for seizures “should not jump to the conclusion that they must come off these medications so as not to increase their risk of developing Parkinson’s disease.” She noted that having seizures “can be dangerous – injuries can occur during a seizure, and if a seizure can’t be stopped or a number occur in rapid succession, brain injury may result.”

For these reasons, people with “a tendency to have seizures need to protect themselves with AEDs” and “should certainly reach out to their neurologists with any questions,” Dr. Gilbert said.

The Preventive Neurology Unit is funded by Barts Charity. The Apocrita High Performance Cluster facility, supported by Queen Mary University London Research–IT Services, was used for this research. Dr. Noyce has received grants from Barts Charity, Parkinson’s UK, Cure Parkinson’s, the Michael J. Fox Foundation, Innovate UK, Solvemed, and Alchemab and personal fees from AstraZeneca, AbbVie, Zambon, BIAL, uMedeor, Alchemab, Britannia, and Charco Neurotech outside the submitted work. The other authors’ disclosures are listed on the original article. Dr. Gilbert reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with unrecognized or prodromal Parkinson’s disease experience problems with mobility, muscle weakness, and struggle with other aspects of daily functioning up to 3 years before diagnosis, new research shows.

The new findings come from a large case-control study that analyzed Medicare claims data to evaluate functional limitations in prodromal Parkinson’s disease, leading the investigators to suggest prodromal Parkinson’s disease should be recognized as a distinct disease stage.

“It’s increasingly recognized as a stage of Parkinson’s and there is an argument here for that,” said lead investigator Cameron Miller-Patterson, MD, assistant professor of neurology at Virginia Commonwealth University, Richmond. “Because we’re finding that people with prodromal Parkinson’s disease may have functional limitations, identifying them sooner and getting them the appropriate symptomatic therapy could be helpful.”

The findings were published online in JAMA Neurology.
 

Improving quality of life

Individuals with prodromal Parkinson’s disease have symptoms of Parkinson’s disease, but not enough to meet diagnostic criteria. However, all patients with prodromal Parkinson’s disease eventually meet that threshold. 

To evaluate whether functional limitations are present in individuals with Parkinson’s disease prior to diagnosis versus the general population, researchers analyzed Medicare-linked data on 6,674 individuals aged 65 years and older who participated in the National Health and Aging Trends Study, a longitudinal survey in the United States. Survey questions evaluated dexterity, eating, mobility, mood, pain, sleep, speech, strength, and vision.

Patients with incident Parkinson’s disease were defined as having two or more Medicare diagnoses. Controls were defined as those with Medicare eligibility at baseline and 2 or more years prior, with no diagnosis.

Compared with individuals who never had Parkinson’s disease, those who eventually received a diagnosis were less likely to report being able to walk 6 blocks (odds ratio, 0.34; 95% confidence interval, 0.15-0.82), stand independently from kneeling (OR, 0.30; 95% CI, 0.11-0.85) or lift a heavy object overhead (OR, 0.36; 95% CI, 0.15-0.87). They were also more likely to report imbalance (OR, 2.77; 95% CI, 1.24-6.20) 3 years prior to diagnosis.

“Generally, we don’t start treating people until we see them in the clinic and give them a diagnosis of Parkinson’s disease,” Dr. Miller-Patterson said. “If we identify them earlier, even before diagnosis, we may be able to improve their quality of life by treating them sooner.”
 

Serving patients better

Better recognition of prodromal Parkinson’s disease could also help identify participants for clinical trials of therapeutics that could slow disease progression, something that is beyond the ability of currently approved medications.

This, and growing support for distinguishing prodromal Parkinson’s disease as an official stage of Parkinson’s disease, makes findings such as these both timely and important, the authors of an accompanying commentary wrote . 

“The recognition of a prodromal period has been viewed as potentially critical to the success of disease-modifying interventions, on the argument that it may be too late to enact meaningful clinical change once symptoms clinically manifest given the degree of neurodegeneration already present,” Ian O. Bledsoe, MD, Weill Institute for Neurosciences, University of California, San Francisco, and coauthors wrote.

One limitation, however, is that the study design didn’t allow researchers to determine if individuals with eventual Parkinson’s disease who reported parkinsonian symptoms had prodromal Parkinson’s disease or undiagnosed disease. The answer would clarify whether prodromal Parkinson’s disease is more common than previously thought or if Parkinson’s disease diagnosis is often delayed for years – or both.

“Despite the limitations of this study, its broader point and importance remain: People appear to have some markers of functional decline before they are diagnosed with Parkinson’s disease,” the editorialists wrote. “Additionally, motor dysfunction may arise at an earlier time point in the disease than we typically think. There is a potential opportunity to serve this population better.”

The study was funded by the National Institutes of Health. Dr. Miller-Patterson reported receiving other NIH grants during the course of the study. Dr. Bledsoe reported personal fees from Boston Scientific, Amneal Pharmaceuticals, IDEO, Accorda, Humancraft.com, and Putnam Associates, as well as grants from the National Institutes of Health, the Michael J. Fox Foundation, and Dystonia Medical.

A version of this article first appeared on Medscape.com.

Patients with unrecognized or prodromal Parkinson’s disease experience problems with mobility, muscle weakness, and struggle with other aspects of daily functioning up to 3 years before diagnosis, new research shows.

The new findings come from a large case-control study that analyzed Medicare claims data to evaluate functional limitations in prodromal Parkinson’s disease, leading the investigators to suggest prodromal Parkinson’s disease should be recognized as a distinct disease stage.

“It’s increasingly recognized as a stage of Parkinson’s and there is an argument here for that,” said lead investigator Cameron Miller-Patterson, MD, assistant professor of neurology at Virginia Commonwealth University, Richmond. “Because we’re finding that people with prodromal Parkinson’s disease may have functional limitations, identifying them sooner and getting them the appropriate symptomatic therapy could be helpful.”

The findings were published online in JAMA Neurology.
 

Improving quality of life

Individuals with prodromal Parkinson’s disease have symptoms of Parkinson’s disease, but not enough to meet diagnostic criteria. However, all patients with prodromal Parkinson’s disease eventually meet that threshold. 

To evaluate whether functional limitations are present in individuals with Parkinson’s disease prior to diagnosis versus the general population, researchers analyzed Medicare-linked data on 6,674 individuals aged 65 years and older who participated in the National Health and Aging Trends Study, a longitudinal survey in the United States. Survey questions evaluated dexterity, eating, mobility, mood, pain, sleep, speech, strength, and vision.

Patients with incident Parkinson’s disease were defined as having two or more Medicare diagnoses. Controls were defined as those with Medicare eligibility at baseline and 2 or more years prior, with no diagnosis.

Compared with individuals who never had Parkinson’s disease, those who eventually received a diagnosis were less likely to report being able to walk 6 blocks (odds ratio, 0.34; 95% confidence interval, 0.15-0.82), stand independently from kneeling (OR, 0.30; 95% CI, 0.11-0.85) or lift a heavy object overhead (OR, 0.36; 95% CI, 0.15-0.87). They were also more likely to report imbalance (OR, 2.77; 95% CI, 1.24-6.20) 3 years prior to diagnosis.

“Generally, we don’t start treating people until we see them in the clinic and give them a diagnosis of Parkinson’s disease,” Dr. Miller-Patterson said. “If we identify them earlier, even before diagnosis, we may be able to improve their quality of life by treating them sooner.”
 

Serving patients better

Better recognition of prodromal Parkinson’s disease could also help identify participants for clinical trials of therapeutics that could slow disease progression, something that is beyond the ability of currently approved medications.

This, and growing support for distinguishing prodromal Parkinson’s disease as an official stage of Parkinson’s disease, makes findings such as these both timely and important, the authors of an accompanying commentary wrote . 

“The recognition of a prodromal period has been viewed as potentially critical to the success of disease-modifying interventions, on the argument that it may be too late to enact meaningful clinical change once symptoms clinically manifest given the degree of neurodegeneration already present,” Ian O. Bledsoe, MD, Weill Institute for Neurosciences, University of California, San Francisco, and coauthors wrote.

One limitation, however, is that the study design didn’t allow researchers to determine if individuals with eventual Parkinson’s disease who reported parkinsonian symptoms had prodromal Parkinson’s disease or undiagnosed disease. The answer would clarify whether prodromal Parkinson’s disease is more common than previously thought or if Parkinson’s disease diagnosis is often delayed for years – or both.

“Despite the limitations of this study, its broader point and importance remain: People appear to have some markers of functional decline before they are diagnosed with Parkinson’s disease,” the editorialists wrote. “Additionally, motor dysfunction may arise at an earlier time point in the disease than we typically think. There is a potential opportunity to serve this population better.”

The study was funded by the National Institutes of Health. Dr. Miller-Patterson reported receiving other NIH grants during the course of the study. Dr. Bledsoe reported personal fees from Boston Scientific, Amneal Pharmaceuticals, IDEO, Accorda, Humancraft.com, and Putnam Associates, as well as grants from the National Institutes of Health, the Michael J. Fox Foundation, and Dystonia Medical.

A version of this article first appeared on Medscape.com.

Patients with unrecognized or prodromal Parkinson’s disease experience problems with mobility, muscle weakness, and struggle with other aspects of daily functioning up to 3 years before diagnosis, new research shows.

The new findings come from a large case-control study that analyzed Medicare claims data to evaluate functional limitations in prodromal Parkinson’s disease, leading the investigators to suggest prodromal Parkinson’s disease should be recognized as a distinct disease stage.

“It’s increasingly recognized as a stage of Parkinson’s and there is an argument here for that,” said lead investigator Cameron Miller-Patterson, MD, assistant professor of neurology at Virginia Commonwealth University, Richmond. “Because we’re finding that people with prodromal Parkinson’s disease may have functional limitations, identifying them sooner and getting them the appropriate symptomatic therapy could be helpful.”

The findings were published online in JAMA Neurology.
 

Improving quality of life

Individuals with prodromal Parkinson’s disease have symptoms of Parkinson’s disease, but not enough to meet diagnostic criteria. However, all patients with prodromal Parkinson’s disease eventually meet that threshold. 

To evaluate whether functional limitations are present in individuals with Parkinson’s disease prior to diagnosis versus the general population, researchers analyzed Medicare-linked data on 6,674 individuals aged 65 years and older who participated in the National Health and Aging Trends Study, a longitudinal survey in the United States. Survey questions evaluated dexterity, eating, mobility, mood, pain, sleep, speech, strength, and vision.

Patients with incident Parkinson’s disease were defined as having two or more Medicare diagnoses. Controls were defined as those with Medicare eligibility at baseline and 2 or more years prior, with no diagnosis.

Compared with individuals who never had Parkinson’s disease, those who eventually received a diagnosis were less likely to report being able to walk 6 blocks (odds ratio, 0.34; 95% confidence interval, 0.15-0.82), stand independently from kneeling (OR, 0.30; 95% CI, 0.11-0.85) or lift a heavy object overhead (OR, 0.36; 95% CI, 0.15-0.87). They were also more likely to report imbalance (OR, 2.77; 95% CI, 1.24-6.20) 3 years prior to diagnosis.

“Generally, we don’t start treating people until we see them in the clinic and give them a diagnosis of Parkinson’s disease,” Dr. Miller-Patterson said. “If we identify them earlier, even before diagnosis, we may be able to improve their quality of life by treating them sooner.”
 

Serving patients better

Better recognition of prodromal Parkinson’s disease could also help identify participants for clinical trials of therapeutics that could slow disease progression, something that is beyond the ability of currently approved medications.

This, and growing support for distinguishing prodromal Parkinson’s disease as an official stage of Parkinson’s disease, makes findings such as these both timely and important, the authors of an accompanying commentary wrote . 

“The recognition of a prodromal period has been viewed as potentially critical to the success of disease-modifying interventions, on the argument that it may be too late to enact meaningful clinical change once symptoms clinically manifest given the degree of neurodegeneration already present,” Ian O. Bledsoe, MD, Weill Institute for Neurosciences, University of California, San Francisco, and coauthors wrote.

One limitation, however, is that the study design didn’t allow researchers to determine if individuals with eventual Parkinson’s disease who reported parkinsonian symptoms had prodromal Parkinson’s disease or undiagnosed disease. The answer would clarify whether prodromal Parkinson’s disease is more common than previously thought or if Parkinson’s disease diagnosis is often delayed for years – or both.

“Despite the limitations of this study, its broader point and importance remain: People appear to have some markers of functional decline before they are diagnosed with Parkinson’s disease,” the editorialists wrote. “Additionally, motor dysfunction may arise at an earlier time point in the disease than we typically think. There is a potential opportunity to serve this population better.”

The study was funded by the National Institutes of Health. Dr. Miller-Patterson reported receiving other NIH grants during the course of the study. Dr. Bledsoe reported personal fees from Boston Scientific, Amneal Pharmaceuticals, IDEO, Accorda, Humancraft.com, and Putnam Associates, as well as grants from the National Institutes of Health, the Michael J. Fox Foundation, and Dystonia Medical.

A version of this article first appeared on Medscape.com.

The number of U.S. patients diagnosed with Parkinson’s disease each year is about 50% higher than previously thought, according to new research that investigators say highlights the growing strain on clinical services and the need for more research funding.

In an analysis of five databases and more than 15 million people, about 60,000-90,000 individuals older than 45 years are estimated to be diagnosed with Parkinson’s disease each year – which is far more than the previous estimate of around 40,000-60,000 new cases annually.

This is the latest study to update decades-old epidemiologic data on Parkinson’s disease incidence and prevalence. Previous incidence rates came from small, single-population studies that are now more than 25 years old.

“In the advocacy community, we’ve been earnest about the impact of people living with Parkinson’s disease, and what we really lacked was sufficient data to be able to demonstrate the urgency of our need,” said study coinvestigator James Beck, PhD, chief scientific officer at the Parkinson’s Foundation, New York.

“We wanted to revise these numbers, highlight that they are larger than people anticipated, and use it as a call to action to change the approach we have toward Parkinson’s,” Dr. Beck said.

The findings were published online in NPJ Parkinson’s Disease.
 

Updating an outdated model

The study builds on the Parkinson’s Prevalence Project, a 2018 initiative that used a new model to calculate Parkinson’s disease prevalence. Before then, federal prevalence data was based on a 40-year-old study of just 26 Parkinson’s disease cases in one small county in rural Mississippi.

Dr. Beck and others used a more sophisticated model, using data from five separate cohort studies. They estimated the total number of patients living with Parkinson’s disease in the United States to be 930,000, which is far higher than the 650,000 the old model predicted.

Researchers then moved on to the current project, developing a new method to estimate Parkinson’s disease incidence.

The project included 2012 data on more than 15 million individuals in the United States and Canada. The investigators drew from three large insurance databases (Kaiser Permanente Northern California, Ontario Health Care, and Medicare) and two long-term epidemiologic studies (the Honolulu-Asia Aging Study and the Rochester Epidemiology Project).

On the basis of their analysis, the investigators proposed a working Parkinson’s disease incident rate estimate of 47-77 cases per 100,000 people aged 45 years or older. Limiting the analysis to those aged 65 or older raised the incidence to 108-212 per 100,000 people.

That translates to 60,000-95,000 new cases each year among adults aged 45 years or older. Using the Medicare administrative database alone for this same time period suggests an annual incidence of nearly 90,000 for individuals aged 65 or older.

“The numbers we’re proposing are conservative,” Dr. Beck said. “The true numbers are probably north of 90,000.”

Incidence rates increased with age and were higher in men. The researchers also identified clusters of counties with higher incidence rates in parts of the country called the “Parkinson’s belt.”

That geographic area mirrors the Rust Belt and includes parts of the Northeastern and Midwestern United States with a long history of industrial manufacturing that used heavy metals and industrial solvents, which are environmental factors linked to risk for Parkinson’s disease.

Cases were also higher in southern California, southeastern Texas, and Florida – agricultural regions with high pesticide use, which is also a risk factor for Parkinson’s disease. Central Pennsylvania also had higher incidence rates.
 

Why the increase?

The increase in cases could be the result of the more comprehensive estimation model used, the researchers noted. Or it could be improved detection, the aging population, a rise in sedentary lifestyles, increased exposure to environmental risk factors, or even the sharp decline in smoking in the United States, as some studies have shown that smokers have a lower Parkinson’s disease risk.

“The short answer is, we don’t know; and the long answer is, it’s all the above,” Dr. Beck said.

Although about 15% of Parkinson’s disease cases have a genetic basis, the cause is unknown in the majority of cases. In addition, diagnosis is difficult because there is no blood test or scan that detects the disease.

“Diagnosis requires a skilled clinician with real familiarity with Parkinson’s. And we have a real shortage of neurologists in this country to not only be able to diagnose but also to treat the condition,” Dr. Beck said.

That was one motivation for doing the study: to highlight what experts say is a pending clinical crisis for patients with Parkinson’s disease, he added.

The investigators also wanted to raise awareness about the scope of the disorder – not just about prevalence and incidence but also what those data mean for the health care industry, research aims, drug development and health care coverage, and policies.

In a 2020 study, the same researchers calculated a cost of $52 billion per year for medical and nonmedical costs related to Parkinson’s disease, which works out to about $26,000 per year per patient. That figure is expected to surpass $79 billion by 2030.

“This is an urgent condition for many people who live with the disease. And to the extent we can get our country to recognize that and really make the investment now, this is an area where a stitch in time saves nine,” Dr. Beck said.

“If we can invest some money now, we have a chance to really make a difference in the future,” he added.
 

‘Groundbreaking’ findings

Commenting on the findings, Jori Fleisher, MD, MSCE, associate professor of neurological sciences at Rush University Medical Center, Chicago, called the results “groundbreaking” and said that they validate what clinicians have been seeing in real-world practice.

“The findings reflect what a lot of us in practice have been appreciating anecdotally, which is that it seems that Parkinson’s is being diagnosed more frequently and that the incidence has been rising,” said Dr. Fleisher, who was not involved with the study.

She noted that the use of multiple datasets is one element of the methodology that makes the data so significant.

“There has been great work out of individual centers; but no matter how good your study methods are within that one population, you’re drawing conclusions based on that one population,” Dr. Fleisher said.

This research, together with the previous work by the group on prevalence data, could go a long way toward raising awareness about the scope of Parkinson’s disease in the United States – which could lead to earlier diagnosis, more research funding, and increased attention on the need for more clinicians who specialize in movement disorders, she added.

“This should increase research funding across the spectrum, including everything from the basic science to translational research, clinical research and implementation, and health services research,” Dr. Fleisher said.

The study was supported by the Parkinson’s Foundation, The Michael J. Fox Foundation for Parkinson’s Research, and the Institute for Clinical Evaluative Sciences. Dr. Beck and Dr. Fleisher reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The number of U.S. patients diagnosed with Parkinson’s disease each year is about 50% higher than previously thought, according to new research that investigators say highlights the growing strain on clinical services and the need for more research funding.

In an analysis of five databases and more than 15 million people, about 60,000-90,000 individuals older than 45 years are estimated to be diagnosed with Parkinson’s disease each year – which is far more than the previous estimate of around 40,000-60,000 new cases annually.

This is the latest study to update decades-old epidemiologic data on Parkinson’s disease incidence and prevalence. Previous incidence rates came from small, single-population studies that are now more than 25 years old.

“In the advocacy community, we’ve been earnest about the impact of people living with Parkinson’s disease, and what we really lacked was sufficient data to be able to demonstrate the urgency of our need,” said study coinvestigator James Beck, PhD, chief scientific officer at the Parkinson’s Foundation, New York.

“We wanted to revise these numbers, highlight that they are larger than people anticipated, and use it as a call to action to change the approach we have toward Parkinson’s,” Dr. Beck said.

The findings were published online in NPJ Parkinson’s Disease.
 

Updating an outdated model

The study builds on the Parkinson’s Prevalence Project, a 2018 initiative that used a new model to calculate Parkinson’s disease prevalence. Before then, federal prevalence data was based on a 40-year-old study of just 26 Parkinson’s disease cases in one small county in rural Mississippi.

Dr. Beck and others used a more sophisticated model, using data from five separate cohort studies. They estimated the total number of patients living with Parkinson’s disease in the United States to be 930,000, which is far higher than the 650,000 the old model predicted.

Researchers then moved on to the current project, developing a new method to estimate Parkinson’s disease incidence.

The project included 2012 data on more than 15 million individuals in the United States and Canada. The investigators drew from three large insurance databases (Kaiser Permanente Northern California, Ontario Health Care, and Medicare) and two long-term epidemiologic studies (the Honolulu-Asia Aging Study and the Rochester Epidemiology Project).

On the basis of their analysis, the investigators proposed a working Parkinson’s disease incident rate estimate of 47-77 cases per 100,000 people aged 45 years or older. Limiting the analysis to those aged 65 or older raised the incidence to 108-212 per 100,000 people.

That translates to 60,000-95,000 new cases each year among adults aged 45 years or older. Using the Medicare administrative database alone for this same time period suggests an annual incidence of nearly 90,000 for individuals aged 65 or older.

“The numbers we’re proposing are conservative,” Dr. Beck said. “The true numbers are probably north of 90,000.”

Incidence rates increased with age and were higher in men. The researchers also identified clusters of counties with higher incidence rates in parts of the country called the “Parkinson’s belt.”

That geographic area mirrors the Rust Belt and includes parts of the Northeastern and Midwestern United States with a long history of industrial manufacturing that used heavy metals and industrial solvents, which are environmental factors linked to risk for Parkinson’s disease.

Cases were also higher in southern California, southeastern Texas, and Florida – agricultural regions with high pesticide use, which is also a risk factor for Parkinson’s disease. Central Pennsylvania also had higher incidence rates.
 

Why the increase?

The increase in cases could be the result of the more comprehensive estimation model used, the researchers noted. Or it could be improved detection, the aging population, a rise in sedentary lifestyles, increased exposure to environmental risk factors, or even the sharp decline in smoking in the United States, as some studies have shown that smokers have a lower Parkinson’s disease risk.

“The short answer is, we don’t know; and the long answer is, it’s all the above,” Dr. Beck said.

Although about 15% of Parkinson’s disease cases have a genetic basis, the cause is unknown in the majority of cases. In addition, diagnosis is difficult because there is no blood test or scan that detects the disease.

“Diagnosis requires a skilled clinician with real familiarity with Parkinson’s. And we have a real shortage of neurologists in this country to not only be able to diagnose but also to treat the condition,” Dr. Beck said.

That was one motivation for doing the study: to highlight what experts say is a pending clinical crisis for patients with Parkinson’s disease, he added.

The investigators also wanted to raise awareness about the scope of the disorder – not just about prevalence and incidence but also what those data mean for the health care industry, research aims, drug development and health care coverage, and policies.

In a 2020 study, the same researchers calculated a cost of $52 billion per year for medical and nonmedical costs related to Parkinson’s disease, which works out to about $26,000 per year per patient. That figure is expected to surpass $79 billion by 2030.

“This is an urgent condition for many people who live with the disease. And to the extent we can get our country to recognize that and really make the investment now, this is an area where a stitch in time saves nine,” Dr. Beck said.

“If we can invest some money now, we have a chance to really make a difference in the future,” he added.
 

‘Groundbreaking’ findings

Commenting on the findings, Jori Fleisher, MD, MSCE, associate professor of neurological sciences at Rush University Medical Center, Chicago, called the results “groundbreaking” and said that they validate what clinicians have been seeing in real-world practice.

“The findings reflect what a lot of us in practice have been appreciating anecdotally, which is that it seems that Parkinson’s is being diagnosed more frequently and that the incidence has been rising,” said Dr. Fleisher, who was not involved with the study.

She noted that the use of multiple datasets is one element of the methodology that makes the data so significant.

“There has been great work out of individual centers; but no matter how good your study methods are within that one population, you’re drawing conclusions based on that one population,” Dr. Fleisher said.

This research, together with the previous work by the group on prevalence data, could go a long way toward raising awareness about the scope of Parkinson’s disease in the United States – which could lead to earlier diagnosis, more research funding, and increased attention on the need for more clinicians who specialize in movement disorders, she added.

“This should increase research funding across the spectrum, including everything from the basic science to translational research, clinical research and implementation, and health services research,” Dr. Fleisher said.

The study was supported by the Parkinson’s Foundation, The Michael J. Fox Foundation for Parkinson’s Research, and the Institute for Clinical Evaluative Sciences. Dr. Beck and Dr. Fleisher reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The number of U.S. patients diagnosed with Parkinson’s disease each year is about 50% higher than previously thought, according to new research that investigators say highlights the growing strain on clinical services and the need for more research funding.

In an analysis of five databases and more than 15 million people, about 60,000-90,000 individuals older than 45 years are estimated to be diagnosed with Parkinson’s disease each year – which is far more than the previous estimate of around 40,000-60,000 new cases annually.

This is the latest study to update decades-old epidemiologic data on Parkinson’s disease incidence and prevalence. Previous incidence rates came from small, single-population studies that are now more than 25 years old.

“In the advocacy community, we’ve been earnest about the impact of people living with Parkinson’s disease, and what we really lacked was sufficient data to be able to demonstrate the urgency of our need,” said study coinvestigator James Beck, PhD, chief scientific officer at the Parkinson’s Foundation, New York.

“We wanted to revise these numbers, highlight that they are larger than people anticipated, and use it as a call to action to change the approach we have toward Parkinson’s,” Dr. Beck said.

The findings were published online in NPJ Parkinson’s Disease.
 

Updating an outdated model

The study builds on the Parkinson’s Prevalence Project, a 2018 initiative that used a new model to calculate Parkinson’s disease prevalence. Before then, federal prevalence data was based on a 40-year-old study of just 26 Parkinson’s disease cases in one small county in rural Mississippi.

Dr. Beck and others used a more sophisticated model, using data from five separate cohort studies. They estimated the total number of patients living with Parkinson’s disease in the United States to be 930,000, which is far higher than the 650,000 the old model predicted.

Researchers then moved on to the current project, developing a new method to estimate Parkinson’s disease incidence.

The project included 2012 data on more than 15 million individuals in the United States and Canada. The investigators drew from three large insurance databases (Kaiser Permanente Northern California, Ontario Health Care, and Medicare) and two long-term epidemiologic studies (the Honolulu-Asia Aging Study and the Rochester Epidemiology Project).

On the basis of their analysis, the investigators proposed a working Parkinson’s disease incident rate estimate of 47-77 cases per 100,000 people aged 45 years or older. Limiting the analysis to those aged 65 or older raised the incidence to 108-212 per 100,000 people.

That translates to 60,000-95,000 new cases each year among adults aged 45 years or older. Using the Medicare administrative database alone for this same time period suggests an annual incidence of nearly 90,000 for individuals aged 65 or older.

“The numbers we’re proposing are conservative,” Dr. Beck said. “The true numbers are probably north of 90,000.”

Incidence rates increased with age and were higher in men. The researchers also identified clusters of counties with higher incidence rates in parts of the country called the “Parkinson’s belt.”

That geographic area mirrors the Rust Belt and includes parts of the Northeastern and Midwestern United States with a long history of industrial manufacturing that used heavy metals and industrial solvents, which are environmental factors linked to risk for Parkinson’s disease.

Cases were also higher in southern California, southeastern Texas, and Florida – agricultural regions with high pesticide use, which is also a risk factor for Parkinson’s disease. Central Pennsylvania also had higher incidence rates.
 

Why the increase?

The increase in cases could be the result of the more comprehensive estimation model used, the researchers noted. Or it could be improved detection, the aging population, a rise in sedentary lifestyles, increased exposure to environmental risk factors, or even the sharp decline in smoking in the United States, as some studies have shown that smokers have a lower Parkinson’s disease risk.

“The short answer is, we don’t know; and the long answer is, it’s all the above,” Dr. Beck said.

Although about 15% of Parkinson’s disease cases have a genetic basis, the cause is unknown in the majority of cases. In addition, diagnosis is difficult because there is no blood test or scan that detects the disease.

“Diagnosis requires a skilled clinician with real familiarity with Parkinson’s. And we have a real shortage of neurologists in this country to not only be able to diagnose but also to treat the condition,” Dr. Beck said.

That was one motivation for doing the study: to highlight what experts say is a pending clinical crisis for patients with Parkinson’s disease, he added.

The investigators also wanted to raise awareness about the scope of the disorder – not just about prevalence and incidence but also what those data mean for the health care industry, research aims, drug development and health care coverage, and policies.

In a 2020 study, the same researchers calculated a cost of $52 billion per year for medical and nonmedical costs related to Parkinson’s disease, which works out to about $26,000 per year per patient. That figure is expected to surpass $79 billion by 2030.

“This is an urgent condition for many people who live with the disease. And to the extent we can get our country to recognize that and really make the investment now, this is an area where a stitch in time saves nine,” Dr. Beck said.

“If we can invest some money now, we have a chance to really make a difference in the future,” he added.
 

‘Groundbreaking’ findings

Commenting on the findings, Jori Fleisher, MD, MSCE, associate professor of neurological sciences at Rush University Medical Center, Chicago, called the results “groundbreaking” and said that they validate what clinicians have been seeing in real-world practice.

“The findings reflect what a lot of us in practice have been appreciating anecdotally, which is that it seems that Parkinson’s is being diagnosed more frequently and that the incidence has been rising,” said Dr. Fleisher, who was not involved with the study.

She noted that the use of multiple datasets is one element of the methodology that makes the data so significant.

“There has been great work out of individual centers; but no matter how good your study methods are within that one population, you’re drawing conclusions based on that one population,” Dr. Fleisher said.

This research, together with the previous work by the group on prevalence data, could go a long way toward raising awareness about the scope of Parkinson’s disease in the United States – which could lead to earlier diagnosis, more research funding, and increased attention on the need for more clinicians who specialize in movement disorders, she added.

“This should increase research funding across the spectrum, including everything from the basic science to translational research, clinical research and implementation, and health services research,” Dr. Fleisher said.

The study was supported by the Parkinson’s Foundation, The Michael J. Fox Foundation for Parkinson’s Research, and the Institute for Clinical Evaluative Sciences. Dr. Beck and Dr. Fleisher reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.