Successful deep brain stimulation of the subthalamic nucleus may have unforeseen effects on the ability to swim in some patients with Parkinson’s disease, according to findings from a case series of nine patients published in Neurology.

All nine patients in the report were experienced swimmers, including two who competed in several competition-level races. They reported losing their ability to swim after successful deep brain stimulation of the subthalamic nucleus (STN-DBS) procedures. The Neurology paper focuses on three of the patients.

All of the patients achieved good to excellent motor control and cut their L-dopa dosage by impressive amounts. But they also lost the ability to coordinate limb movement when in the water, reported Daniel Waldvogel, MD, of the University of Zurich, and associates.

“All found their ability to swim came back immediately, with improved coordination of the limbs,” when stimulation was discontinued, the team noted. But soon after the stimulation ceased, their motor symptoms also rapidly returned, leading all to resume continuous stimulation.

One possible explanation is that STN-DBS does not strongly improve dopamine levels in the supplementary motor area, which controls independent limb movements.

It “may be that DBS affects the supplementary motor area (SMA) differently than levodopa. The SMA is a main output area of the basal ganglia, with connections to the primary motor cortex and the spinal cord,” wrote Dr. Waldvogel and associates. “Functionally, the SMA is thought to be crucial for facilitating independent movements of the limbs, which is a key requirement for swimming.”

Although the SMA also partly manages gait, walking was unaffected in all nine of the patients.

The authors described three patients in more detail:

• Case 1 was a 69-year-old man who was a proficient swimmer before DBS. His Unified Parkinson’s Disease Rating Scale (UPDRS) motor score on medication fell from 28 with dyskinesia before DBS to 17 after DBS, and his levodopa-equivalent dosage declined from 1,570 mg to 920 mg. The man almost drowned after he jumped into a lake and had to be rescued by another swimmer.
• Case 4 was a 59-year-old woman who was an accomplished and competitive swimmer and had been swimming up until the DBS procedure. After DBS, her UPDRS motor score on medication fell from 9 with dyskinesia to 6, and her levodopa-equivalent dosage dropped from 825 mg to 150 mg. She had good motor outcome after DBS but lost the ability to swim. “She regularly practiced swimming with her physiotherapist, but never came close to her previous level,” the authors said.
• Case 5 was a 61-year-old woman who was a competitive swimmer, including swimming across Lake Zurich, and held a lifesaving certification. Her UPDRS motor score on medication fell from 11 with dyskinesia to 9, and her levodopa-equivalent dosage decreased from 800 mg to 180 mg. After DBS, she could swim only a quarter of a kilometer and complained of “awkward posture” during her efforts.

The phenomenon has been reported just one other time by a group from the University of Western Australia. This reported patient was a 68-year-old man with a 5-year history of medication-refractory, tremor-predominant Parkinson’s. He received DBS of the posterior subthalamic area (PSA-DBS).

The patient was a dedicated lap swimmer at his local pool. When he returned to his hobby, “he quickly realized he could not propel himself adequately and that he required assistance to get to safety. In a supervised swimming situation, he was unable to float or perform freestyle, breaststroke, or back stroke. With the stimulator turned off for 30 minutes, he regained swimming ability and lost it when the stimulator was turned on.

The Australian team noted that three similar cases presented to them, but they did not discuss those cases in the paper.

Dr. Waldvogel and coauthors wrote that they might also have unreported cases in their cohort of patients with STN-DBS.

“Our cohort of patients with PD who underwent STN-DBS at the time of this retrospective study consisted of 217 patients, but we did not assess patients systematically for their swimming skills or loss thereof,” the authors said. “Until the mechanism of the reported deterioration of the ability to swim after STN-DBS is elucidated, it is crucial that we advise patients of the potential risk of drowning and the need for a carefully supervised assessment of their swimming skills before going into deep water.”

The report received no funding, and one author disclosed financial relationships with industry.

[email protected]

SOURCE: Waldvogel D et al Neurology. 2019 Nov 27. doi: 10.1212/WNL.0000000000008664.

Successful deep brain stimulation of the subthalamic nucleus may have unforeseen effects on the ability to swim in some patients with Parkinson’s disease, according to findings from a case series of nine patients published in Neurology.

All nine patients in the report were experienced swimmers, including two who competed in several competition-level races. They reported losing their ability to swim after successful deep brain stimulation of the subthalamic nucleus (STN-DBS) procedures. The Neurology paper focuses on three of the patients.

All of the patients achieved good to excellent motor control and cut their L-dopa dosage by impressive amounts. But they also lost the ability to coordinate limb movement when in the water, reported Daniel Waldvogel, MD, of the University of Zurich, and associates.

“All found their ability to swim came back immediately, with improved coordination of the limbs,” when stimulation was discontinued, the team noted. But soon after the stimulation ceased, their motor symptoms also rapidly returned, leading all to resume continuous stimulation.

One possible explanation is that STN-DBS does not strongly improve dopamine levels in the supplementary motor area, which controls independent limb movements.

It “may be that DBS affects the supplementary motor area (SMA) differently than levodopa. The SMA is a main output area of the basal ganglia, with connections to the primary motor cortex and the spinal cord,” wrote Dr. Waldvogel and associates. “Functionally, the SMA is thought to be crucial for facilitating independent movements of the limbs, which is a key requirement for swimming.”

Although the SMA also partly manages gait, walking was unaffected in all nine of the patients.

The authors described three patients in more detail:

• Case 1 was a 69-year-old man who was a proficient swimmer before DBS. His Unified Parkinson’s Disease Rating Scale (UPDRS) motor score on medication fell from 28 with dyskinesia before DBS to 17 after DBS, and his levodopa-equivalent dosage declined from 1,570 mg to 920 mg. The man almost drowned after he jumped into a lake and had to be rescued by another swimmer.
• Case 4 was a 59-year-old woman who was an accomplished and competitive swimmer and had been swimming up until the DBS procedure. After DBS, her UPDRS motor score on medication fell from 9 with dyskinesia to 6, and her levodopa-equivalent dosage dropped from 825 mg to 150 mg. She had good motor outcome after DBS but lost the ability to swim. “She regularly practiced swimming with her physiotherapist, but never came close to her previous level,” the authors said.
• Case 5 was a 61-year-old woman who was a competitive swimmer, including swimming across Lake Zurich, and held a lifesaving certification. Her UPDRS motor score on medication fell from 11 with dyskinesia to 9, and her levodopa-equivalent dosage decreased from 800 mg to 180 mg. After DBS, she could swim only a quarter of a kilometer and complained of “awkward posture” during her efforts.

The phenomenon has been reported just one other time by a group from the University of Western Australia. This reported patient was a 68-year-old man with a 5-year history of medication-refractory, tremor-predominant Parkinson’s. He received DBS of the posterior subthalamic area (PSA-DBS).

The patient was a dedicated lap swimmer at his local pool. When he returned to his hobby, “he quickly realized he could not propel himself adequately and that he required assistance to get to safety. In a supervised swimming situation, he was unable to float or perform freestyle, breaststroke, or back stroke. With the stimulator turned off for 30 minutes, he regained swimming ability and lost it when the stimulator was turned on.

The Australian team noted that three similar cases presented to them, but they did not discuss those cases in the paper.

Dr. Waldvogel and coauthors wrote that they might also have unreported cases in their cohort of patients with STN-DBS.

“Our cohort of patients with PD who underwent STN-DBS at the time of this retrospective study consisted of 217 patients, but we did not assess patients systematically for their swimming skills or loss thereof,” the authors said. “Until the mechanism of the reported deterioration of the ability to swim after STN-DBS is elucidated, it is crucial that we advise patients of the potential risk of drowning and the need for a carefully supervised assessment of their swimming skills before going into deep water.”

The report received no funding, and one author disclosed financial relationships with industry.

[email protected]

SOURCE: Waldvogel D et al Neurology. 2019 Nov 27. doi: 10.1212/WNL.0000000000008664.

Successful deep brain stimulation of the subthalamic nucleus may have unforeseen effects on the ability to swim in some patients with Parkinson’s disease, according to findings from a case series of nine patients published in Neurology.

All nine patients in the report were experienced swimmers, including two who competed in several competition-level races. They reported losing their ability to swim after successful deep brain stimulation of the subthalamic nucleus (STN-DBS) procedures. The Neurology paper focuses on three of the patients.

All of the patients achieved good to excellent motor control and cut their L-dopa dosage by impressive amounts. But they also lost the ability to coordinate limb movement when in the water, reported Daniel Waldvogel, MD, of the University of Zurich, and associates.

“All found their ability to swim came back immediately, with improved coordination of the limbs,” when stimulation was discontinued, the team noted. But soon after the stimulation ceased, their motor symptoms also rapidly returned, leading all to resume continuous stimulation.

One possible explanation is that STN-DBS does not strongly improve dopamine levels in the supplementary motor area, which controls independent limb movements.

It “may be that DBS affects the supplementary motor area (SMA) differently than levodopa. The SMA is a main output area of the basal ganglia, with connections to the primary motor cortex and the spinal cord,” wrote Dr. Waldvogel and associates. “Functionally, the SMA is thought to be crucial for facilitating independent movements of the limbs, which is a key requirement for swimming.”

Although the SMA also partly manages gait, walking was unaffected in all nine of the patients.

The authors described three patients in more detail:

• Case 1 was a 69-year-old man who was a proficient swimmer before DBS. His Unified Parkinson’s Disease Rating Scale (UPDRS) motor score on medication fell from 28 with dyskinesia before DBS to 17 after DBS, and his levodopa-equivalent dosage declined from 1,570 mg to 920 mg. The man almost drowned after he jumped into a lake and had to be rescued by another swimmer.
• Case 4 was a 59-year-old woman who was an accomplished and competitive swimmer and had been swimming up until the DBS procedure. After DBS, her UPDRS motor score on medication fell from 9 with dyskinesia to 6, and her levodopa-equivalent dosage dropped from 825 mg to 150 mg. She had good motor outcome after DBS but lost the ability to swim. “She regularly practiced swimming with her physiotherapist, but never came close to her previous level,” the authors said.
• Case 5 was a 61-year-old woman who was a competitive swimmer, including swimming across Lake Zurich, and held a lifesaving certification. Her UPDRS motor score on medication fell from 11 with dyskinesia to 9, and her levodopa-equivalent dosage decreased from 800 mg to 180 mg. After DBS, she could swim only a quarter of a kilometer and complained of “awkward posture” during her efforts.

The phenomenon has been reported just one other time by a group from the University of Western Australia. This reported patient was a 68-year-old man with a 5-year history of medication-refractory, tremor-predominant Parkinson’s. He received DBS of the posterior subthalamic area (PSA-DBS).

The patient was a dedicated lap swimmer at his local pool. When he returned to his hobby, “he quickly realized he could not propel himself adequately and that he required assistance to get to safety. In a supervised swimming situation, he was unable to float or perform freestyle, breaststroke, or back stroke. With the stimulator turned off for 30 minutes, he regained swimming ability and lost it when the stimulator was turned on.

The Australian team noted that three similar cases presented to them, but they did not discuss those cases in the paper.

Dr. Waldvogel and coauthors wrote that they might also have unreported cases in their cohort of patients with STN-DBS.

“Our cohort of patients with PD who underwent STN-DBS at the time of this retrospective study consisted of 217 patients, but we did not assess patients systematically for their swimming skills or loss thereof,” the authors said. “Until the mechanism of the reported deterioration of the ability to swim after STN-DBS is elucidated, it is crucial that we advise patients of the potential risk of drowning and the need for a carefully supervised assessment of their swimming skills before going into deep water.”

The report received no funding, and one author disclosed financial relationships with industry.

[email protected]

SOURCE: Waldvogel D et al Neurology. 2019 Nov 27. doi: 10.1212/WNL.0000000000008664.

Key clinical point: Little is known about what factors predict the progression of cognitive impairment (CI) and progression after a diagnosis of multiple sclerosis (MS).

Major finding: Twenty-two percent of patients had CI at baseline in newly diagnosed MS patients. At follow-up, only 14% of patients had CI. Cognitive changes within 1 year of follow-up could not be determined by baseline characteristics or initiation of treatment.

Study details: Demographic, clinical, and conventional MRI markers at baseline were investigated for CI and changes in 1,123 patients from a multicenter cohort study.

Disclosures: “The German National MS cohort and KKNMS are supported by grants from the German Federal Ministry for Education and Research.” Several study investigators reported received financial support and grants from pharmaceutical agencies.

Citation: Johnen A, et al. J Neurol. 2019 Feb;266(2):386-397. doi: 10.1007/s00415-018-9142-y.

Key clinical point: Little is known about what factors predict the progression of cognitive impairment (CI) and progression after a diagnosis of multiple sclerosis (MS).

Major finding: Twenty-two percent of patients had CI at baseline in newly diagnosed MS patients. At follow-up, only 14% of patients had CI. Cognitive changes within 1 year of follow-up could not be determined by baseline characteristics or initiation of treatment.

Study details: Demographic, clinical, and conventional MRI markers at baseline were investigated for CI and changes in 1,123 patients from a multicenter cohort study.

Disclosures: “The German National MS cohort and KKNMS are supported by grants from the German Federal Ministry for Education and Research.” Several study investigators reported received financial support and grants from pharmaceutical agencies.

Citation: Johnen A, et al. J Neurol. 2019 Feb;266(2):386-397. doi: 10.1007/s00415-018-9142-y.

Key clinical point: Little is known about what factors predict the progression of cognitive impairment (CI) and progression after a diagnosis of multiple sclerosis (MS).

Major finding: Twenty-two percent of patients had CI at baseline in newly diagnosed MS patients. At follow-up, only 14% of patients had CI. Cognitive changes within 1 year of follow-up could not be determined by baseline characteristics or initiation of treatment.

Study details: Demographic, clinical, and conventional MRI markers at baseline were investigated for CI and changes in 1,123 patients from a multicenter cohort study.

Disclosures: “The German National MS cohort and KKNMS are supported by grants from the German Federal Ministry for Education and Research.” Several study investigators reported received financial support and grants from pharmaceutical agencies.

Citation: Johnen A, et al. J Neurol. 2019 Feb;266(2):386-397. doi: 10.1007/s00415-018-9142-y.

Key clinical point: Better management and treatment of diabetes and anxiety in MS patients may help improve cognition.

Major finding: Of 111 patients with relapsing remitting MS (majority were women with a mean age of 50 years), 22.7% had hypertension, 10.8% had diabetes, 9.9% had depression, and 9.9% had anxiety disorders.

Study details: Patients completed a psychiatric interview, a comorbidity questionnaire, and cognitive testing. Scores were converted to age-, sex-, and education-adjusted z-scores. Links between diabetes and hypertension and the cognitive z-scores were evaluated.

Disclosures: Authors disclosed receiving research support from various organizations. One author has conducted clinical trials for Biogen Idec and Rouche. Another has served as a consultant for several pharmaceutical companies, and has also received research grants and served on speaker’s bureaus for the industry.

Citation: Marrie, RA, et al.. Mult Scler Relat Disord. 2019 Jan;27:164-170. doi: 10.1016/j.msard.2018.10.018.

Key clinical point: Better management and treatment of diabetes and anxiety in MS patients may help improve cognition.

Major finding: Of 111 patients with relapsing remitting MS (majority were women with a mean age of 50 years), 22.7% had hypertension, 10.8% had diabetes, 9.9% had depression, and 9.9% had anxiety disorders.

Study details: Patients completed a psychiatric interview, a comorbidity questionnaire, and cognitive testing. Scores were converted to age-, sex-, and education-adjusted z-scores. Links between diabetes and hypertension and the cognitive z-scores were evaluated.

Disclosures: Authors disclosed receiving research support from various organizations. One author has conducted clinical trials for Biogen Idec and Rouche. Another has served as a consultant for several pharmaceutical companies, and has also received research grants and served on speaker’s bureaus for the industry.

Citation: Marrie, RA, et al.. Mult Scler Relat Disord. 2019 Jan;27:164-170. doi: 10.1016/j.msard.2018.10.018.

Key clinical point: Better management and treatment of diabetes and anxiety in MS patients may help improve cognition.

Major finding: Of 111 patients with relapsing remitting MS (majority were women with a mean age of 50 years), 22.7% had hypertension, 10.8% had diabetes, 9.9% had depression, and 9.9% had anxiety disorders.

Study details: Patients completed a psychiatric interview, a comorbidity questionnaire, and cognitive testing. Scores were converted to age-, sex-, and education-adjusted z-scores. Links between diabetes and hypertension and the cognitive z-scores were evaluated.

Disclosures: Authors disclosed receiving research support from various organizations. One author has conducted clinical trials for Biogen Idec and Rouche. Another has served as a consultant for several pharmaceutical companies, and has also received research grants and served on speaker’s bureaus for the industry.

Citation: Marrie, RA, et al.. Mult Scler Relat Disord. 2019 Jan;27:164-170. doi: 10.1016/j.msard.2018.10.018.

Key clinical point: More studies are needed with larger samples and more ethnicities to support the study's findings.

Major finding: The FOXP3 gene rs3761548 was found to increase the risk for MS, with a higher risk found in Asian patients.

Study details: This was a meta-analysis of 5 studies from January 1980 to October 2018. The studies were used to evaluate the association between FOXP3 gene polymorphism and MS. For FOXP3 gene rs3761548, there were 1,276 MS patients and 1,447 controls; and for FOXP3 gene rs2232365, there were 600 MS patients and 640 controls.

Disclosures: None.

Citation: Zhang Y, et al. Medicine. 2019 Sep;98(38):e17224. doi: 10.1097/MD.0000000000017224.

Key clinical point: More studies are needed with larger samples and more ethnicities to support the study's findings.

Major finding: The FOXP3 gene rs3761548 was found to increase the risk for MS, with a higher risk found in Asian patients.

Study details: This was a meta-analysis of 5 studies from January 1980 to October 2018. The studies were used to evaluate the association between FOXP3 gene polymorphism and MS. For FOXP3 gene rs3761548, there were 1,276 MS patients and 1,447 controls; and for FOXP3 gene rs2232365, there were 600 MS patients and 640 controls.

Disclosures: None.

Citation: Zhang Y, et al. Medicine. 2019 Sep;98(38):e17224. doi: 10.1097/MD.0000000000017224.

Key clinical point: More studies are needed with larger samples and more ethnicities to support the study's findings.

Major finding: The FOXP3 gene rs3761548 was found to increase the risk for MS, with a higher risk found in Asian patients.

Study details: This was a meta-analysis of 5 studies from January 1980 to October 2018. The studies were used to evaluate the association between FOXP3 gene polymorphism and MS. For FOXP3 gene rs3761548, there were 1,276 MS patients and 1,447 controls; and for FOXP3 gene rs2232365, there were 600 MS patients and 640 controls.

Disclosures: None.

Citation: Zhang Y, et al. Medicine. 2019 Sep;98(38):e17224. doi: 10.1097/MD.0000000000017224.

The use of glucocorticoids was associated with damage accrual independent of serologic or clinical disease activity in patients with systemic lupus erythematosus (SLE), according to recent findings published in The Lancet Rheumatology.

“Disentangling the potential contribution of glucocorticoid use to organ damage in SLE is confounded, in most studies, by the fact that glucocorticoid use is usually associated with active disease. Our study showed that organ damage accrual occurred in a similar proportion of patients without disease activity as in the overall cohort, and that glucocorticoid use was a significant risk factor for damage,” wrote Diane Apostolopoulos, MBBS, of Monash University, Melbourne, and colleagues.

The longitudinal cohort study prospectively enrolled 1,707 patients with SLE from May 2013 to December 2016. Study participants were recruited from 13 institutions throughout Australia and Asia. The researchers defined glucocorticoid use as any exposure and cumulative exposure to prednisolone, in addition to mean time-adjusted daily prednisolone dose. Follow-up assessment occurred at least once every 6 months and varied depending on clinical necessity. At baseline, the researchers collected various demographic information, including smoking status, age, and education level, among others. The primary endpoint measured was organ damage accrual, which was assessed at baseline and annually thereafter. In addition, disease activity was evaluated in two multivariable models using Physician Global Assessment (PGA) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores.

After a median duration of 2.2 years, the researchers found that 82.3% of patients were exposed to prednisolone, and 14.9% of patients had experienced a damage accrual event. In the PGA model, mean time-adjusted PGA score (based on a 0- to 1-unit increase) was associated with damage accrual independent of clinical or serologic disease activity (hazard ratio, 1.05; P = .0012).

In the SLEDAI-2K model, baseline damage scores were independently associated with damage accrual (hazard ratio, 1.32; P = .0427).

In both models, ethnicity (Asian vs. non-Asian), age at study enrollment, and mean time-adjusted prednisolone dose were parameters independently associated with damage accrual.

“Novel findings from this study were that Asian ethnicity was protective when compared with any non-­Asian ethnicity, and that antimalarial usage was not protective for damage accrual,” the researchers wrote.

Despite the novel results, the researchers acknowledged that the protective effects of antimalarials could have gone undetected because of the short duration of follow-up.

In a related editorial, Guillermo Ruiz-Irastorza, MD, PhD, of University of the Basque Country in Bizkaia, Spain, said that the study provides novel data highlighting that glucocorticoid use has the potential to negatively affect the clinical progression of patients with SLE (Lancet Rheumatol. 2019 Nov 25. doi: 10.1016/S2665-9913(19)30132-8).

One question that remains from the current study is how to effectively reduce glucocorticoid-related adverse events, while still managing the disease, he further explained.

“These findings suggest that unnecessary use of glucocorticoids should be avoided in the manage­ment of the disease where possible,” the investigators concluded.

The study was funded by UCB Pharma, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca. The authors reported financial affiliations with Abbott, AbbVie, Astellas, Ayumi Pharmaceutical, Bristol-Myers Squibb, Novartis, Pfizer, and several others.

SOURCE: Apostolopoulos D et al. Lancet Rheumatol. 2019 Nov 25. doi: 10.1016/S2665-9913(19)30105-5.

The use of glucocorticoids was associated with damage accrual independent of serologic or clinical disease activity in patients with systemic lupus erythematosus (SLE), according to recent findings published in The Lancet Rheumatology.

“Disentangling the potential contribution of glucocorticoid use to organ damage in SLE is confounded, in most studies, by the fact that glucocorticoid use is usually associated with active disease. Our study showed that organ damage accrual occurred in a similar proportion of patients without disease activity as in the overall cohort, and that glucocorticoid use was a significant risk factor for damage,” wrote Diane Apostolopoulos, MBBS, of Monash University, Melbourne, and colleagues.

The longitudinal cohort study prospectively enrolled 1,707 patients with SLE from May 2013 to December 2016. Study participants were recruited from 13 institutions throughout Australia and Asia. The researchers defined glucocorticoid use as any exposure and cumulative exposure to prednisolone, in addition to mean time-adjusted daily prednisolone dose. Follow-up assessment occurred at least once every 6 months and varied depending on clinical necessity. At baseline, the researchers collected various demographic information, including smoking status, age, and education level, among others. The primary endpoint measured was organ damage accrual, which was assessed at baseline and annually thereafter. In addition, disease activity was evaluated in two multivariable models using Physician Global Assessment (PGA) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores.

After a median duration of 2.2 years, the researchers found that 82.3% of patients were exposed to prednisolone, and 14.9% of patients had experienced a damage accrual event. In the PGA model, mean time-adjusted PGA score (based on a 0- to 1-unit increase) was associated with damage accrual independent of clinical or serologic disease activity (hazard ratio, 1.05; P = .0012).

In the SLEDAI-2K model, baseline damage scores were independently associated with damage accrual (hazard ratio, 1.32; P = .0427).

In both models, ethnicity (Asian vs. non-Asian), age at study enrollment, and mean time-adjusted prednisolone dose were parameters independently associated with damage accrual.

“Novel findings from this study were that Asian ethnicity was protective when compared with any non-­Asian ethnicity, and that antimalarial usage was not protective for damage accrual,” the researchers wrote.

Despite the novel results, the researchers acknowledged that the protective effects of antimalarials could have gone undetected because of the short duration of follow-up.

In a related editorial, Guillermo Ruiz-Irastorza, MD, PhD, of University of the Basque Country in Bizkaia, Spain, said that the study provides novel data highlighting that glucocorticoid use has the potential to negatively affect the clinical progression of patients with SLE (Lancet Rheumatol. 2019 Nov 25. doi: 10.1016/S2665-9913(19)30132-8).

One question that remains from the current study is how to effectively reduce glucocorticoid-related adverse events, while still managing the disease, he further explained.

“These findings suggest that unnecessary use of glucocorticoids should be avoided in the manage­ment of the disease where possible,” the investigators concluded.

The study was funded by UCB Pharma, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca. The authors reported financial affiliations with Abbott, AbbVie, Astellas, Ayumi Pharmaceutical, Bristol-Myers Squibb, Novartis, Pfizer, and several others.

SOURCE: Apostolopoulos D et al. Lancet Rheumatol. 2019 Nov 25. doi: 10.1016/S2665-9913(19)30105-5.

The use of glucocorticoids was associated with damage accrual independent of serologic or clinical disease activity in patients with systemic lupus erythematosus (SLE), according to recent findings published in The Lancet Rheumatology.

“Disentangling the potential contribution of glucocorticoid use to organ damage in SLE is confounded, in most studies, by the fact that glucocorticoid use is usually associated with active disease. Our study showed that organ damage accrual occurred in a similar proportion of patients without disease activity as in the overall cohort, and that glucocorticoid use was a significant risk factor for damage,” wrote Diane Apostolopoulos, MBBS, of Monash University, Melbourne, and colleagues.

The longitudinal cohort study prospectively enrolled 1,707 patients with SLE from May 2013 to December 2016. Study participants were recruited from 13 institutions throughout Australia and Asia. The researchers defined glucocorticoid use as any exposure and cumulative exposure to prednisolone, in addition to mean time-adjusted daily prednisolone dose. Follow-up assessment occurred at least once every 6 months and varied depending on clinical necessity. At baseline, the researchers collected various demographic information, including smoking status, age, and education level, among others. The primary endpoint measured was organ damage accrual, which was assessed at baseline and annually thereafter. In addition, disease activity was evaluated in two multivariable models using Physician Global Assessment (PGA) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores.

After a median duration of 2.2 years, the researchers found that 82.3% of patients were exposed to prednisolone, and 14.9% of patients had experienced a damage accrual event. In the PGA model, mean time-adjusted PGA score (based on a 0- to 1-unit increase) was associated with damage accrual independent of clinical or serologic disease activity (hazard ratio, 1.05; P = .0012).

In the SLEDAI-2K model, baseline damage scores were independently associated with damage accrual (hazard ratio, 1.32; P = .0427).

In both models, ethnicity (Asian vs. non-Asian), age at study enrollment, and mean time-adjusted prednisolone dose were parameters independently associated with damage accrual.

“Novel findings from this study were that Asian ethnicity was protective when compared with any non-­Asian ethnicity, and that antimalarial usage was not protective for damage accrual,” the researchers wrote.

Despite the novel results, the researchers acknowledged that the protective effects of antimalarials could have gone undetected because of the short duration of follow-up.

In a related editorial, Guillermo Ruiz-Irastorza, MD, PhD, of University of the Basque Country in Bizkaia, Spain, said that the study provides novel data highlighting that glucocorticoid use has the potential to negatively affect the clinical progression of patients with SLE (Lancet Rheumatol. 2019 Nov 25. doi: 10.1016/S2665-9913(19)30132-8).

One question that remains from the current study is how to effectively reduce glucocorticoid-related adverse events, while still managing the disease, he further explained.

“These findings suggest that unnecessary use of glucocorticoids should be avoided in the manage­ment of the disease where possible,” the investigators concluded.

The study was funded by UCB Pharma, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca. The authors reported financial affiliations with Abbott, AbbVie, Astellas, Ayumi Pharmaceutical, Bristol-Myers Squibb, Novartis, Pfizer, and several others.

SOURCE: Apostolopoulos D et al. Lancet Rheumatol. 2019 Nov 25. doi: 10.1016/S2665-9913(19)30105-5.

Key clinical point: The 12-week injection cycle of Onabotulinumtoxin A (OnabotA) may need to be reconsidered.

Major finding: The study of 98 patients and 471 treatment cycles found that 43 patients experienced one or more wearing-off-effect (WOE) events (worsening headaches and neck pain). Of those patients, 24 reported 1 WOE event and 19 patients reported 2 or more WOEs. Almost 32% of patients used abortive therapy to manage their WOEs.

Study details: This was a retrospective review of patients with worsening headache variables and neck pain who received OnabotA for their chronic migraine in treatment cycles.

Disclosures: Dr. Khan received honorarium for Depomed, Inc. and Promius Pharma while conducting the study.

Citation: Khan FA, et al. Headache. 2019 Nov 22. doi: 10.1111/head.13713. [Epub ahead of print].

Key clinical point: The 12-week injection cycle of Onabotulinumtoxin A (OnabotA) may need to be reconsidered.

Major finding: The study of 98 patients and 471 treatment cycles found that 43 patients experienced one or more wearing-off-effect (WOE) events (worsening headaches and neck pain). Of those patients, 24 reported 1 WOE event and 19 patients reported 2 or more WOEs. Almost 32% of patients used abortive therapy to manage their WOEs.

Study details: This was a retrospective review of patients with worsening headache variables and neck pain who received OnabotA for their chronic migraine in treatment cycles.

Disclosures: Dr. Khan received honorarium for Depomed, Inc. and Promius Pharma while conducting the study.

Citation: Khan FA, et al. Headache. 2019 Nov 22. doi: 10.1111/head.13713. [Epub ahead of print].

Key clinical point: The 12-week injection cycle of Onabotulinumtoxin A (OnabotA) may need to be reconsidered.

Major finding: The study of 98 patients and 471 treatment cycles found that 43 patients experienced one or more wearing-off-effect (WOE) events (worsening headaches and neck pain). Of those patients, 24 reported 1 WOE event and 19 patients reported 2 or more WOEs. Almost 32% of patients used abortive therapy to manage their WOEs.

Study details: This was a retrospective review of patients with worsening headache variables and neck pain who received OnabotA for their chronic migraine in treatment cycles.

Disclosures: Dr. Khan received honorarium for Depomed, Inc. and Promius Pharma while conducting the study.

Citation: Khan FA, et al. Headache. 2019 Nov 22. doi: 10.1111/head.13713. [Epub ahead of print].

Key clinical point: Onabotulinumtoxin A (OnabotA) may decrease migraine days by 50% or more.

Major finding: Of 112 patients with chronic migraine (100 female), 96 responded positively to OnabotA, resulting in decreased migraine days by at least 50%. Having a dependent personality trait was linked to treatment nonresponse.

Study details: This was a case-control observational study of chronic migraine patients that received two or more treatment cycles of OnabotA.

Disclosures: None.

Citation: Gonzalez-Martinez A, et al. Headache. 2019 Nov 6. doi: 10.1111/head.13693. [Epub ahead of print].

Key clinical point: Onabotulinumtoxin A (OnabotA) may decrease migraine days by 50% or more.

Major finding: Of 112 patients with chronic migraine (100 female), 96 responded positively to OnabotA, resulting in decreased migraine days by at least 50%. Having a dependent personality trait was linked to treatment nonresponse.

Study details: This was a case-control observational study of chronic migraine patients that received two or more treatment cycles of OnabotA.

Disclosures: None.

Citation: Gonzalez-Martinez A, et al. Headache. 2019 Nov 6. doi: 10.1111/head.13693. [Epub ahead of print].

Key clinical point: Onabotulinumtoxin A (OnabotA) may decrease migraine days by 50% or more.

Major finding: Of 112 patients with chronic migraine (100 female), 96 responded positively to OnabotA, resulting in decreased migraine days by at least 50%. Having a dependent personality trait was linked to treatment nonresponse.

Study details: This was a case-control observational study of chronic migraine patients that received two or more treatment cycles of OnabotA.

Disclosures: None.

Citation: Gonzalez-Martinez A, et al. Headache. 2019 Nov 6. doi: 10.1111/head.13693. [Epub ahead of print].

Key clinical point: Vitamin D supplementation may decrease the frequency, severity, and duration of migraines.

Major finding: Significantly lower 25 (OH)-vitamin D levels were found in patients with migraine, compared with healthy controls. Migraine patients with low vitamin D levels had a higher incidence of aura, phonophobia/photophobia, autonomic manifestations, allodynia, and medication resistance.

Study details: This was a case-control study of 40 patients with migraine, compared with 40 healthy control patients. Patient history was taken including headache characteristics, MIGSEV, and HIT-6 scores. Each patient’s serum 25 (OH)-vitamin D level was measured.

Disclosures: None.

Citation: Hussein M, et al. J Pain Res. 2019 Aug 20;12:2529-36. doi: 10.2147/JPR.S216314. eCollection 2019.

Key clinical point: Vitamin D supplementation may decrease the frequency, severity, and duration of migraines.

Major finding: Significantly lower 25 (OH)-vitamin D levels were found in patients with migraine, compared with healthy controls. Migraine patients with low vitamin D levels had a higher incidence of aura, phonophobia/photophobia, autonomic manifestations, allodynia, and medication resistance.

Study details: This was a case-control study of 40 patients with migraine, compared with 40 healthy control patients. Patient history was taken including headache characteristics, MIGSEV, and HIT-6 scores. Each patient’s serum 25 (OH)-vitamin D level was measured.

Disclosures: None.

Citation: Hussein M, et al. J Pain Res. 2019 Aug 20;12:2529-36. doi: 10.2147/JPR.S216314. eCollection 2019.

Key clinical point: Vitamin D supplementation may decrease the frequency, severity, and duration of migraines.

Major finding: Significantly lower 25 (OH)-vitamin D levels were found in patients with migraine, compared with healthy controls. Migraine patients with low vitamin D levels had a higher incidence of aura, phonophobia/photophobia, autonomic manifestations, allodynia, and medication resistance.

Study details: This was a case-control study of 40 patients with migraine, compared with 40 healthy control patients. Patient history was taken including headache characteristics, MIGSEV, and HIT-6 scores. Each patient’s serum 25 (OH)-vitamin D level was measured.

Disclosures: None.

Citation: Hussein M, et al. J Pain Res. 2019 Aug 20;12:2529-36. doi: 10.2147/JPR.S216314. eCollection 2019.

Certain types of oral antibiotics seem to be associated with an elevated risk of Parkinson’s disease with a delay that is consistent with the proposed duration of a prodromal period, according to a report published in Movement Disorders. Associations were found for broad-spectrum antibiotics and those that act against anaerobic bacteria and fungi. The timing of antibiotic exposure also seemed to matter.

In a nationwide case-control study, Finnish researchers compared data on antibiotic use in 13,976 individuals diagnosed with Parkinson’s disease between 1998 and 2014 with antibiotic-use data from 40,697 controls. The strongest connection with Parkinson’s disease risk was found for oral exposure to macrolides and lincosamides (adjusted odds ratio up to 1.416). After correction for multiple comparisons, exposure to antianaerobics and tetracyclines 10-15 years before the index date, and antifungal medications 1-5 years before the index date were positively associated with Parkinson’s disease risk. In post hoc analyses, further positive associations were found for broad-spectrum antibiotics.

Tuomas H. Mertsalmi, MD, from the Helsinki University Hospital and coauthors reported that this was the first study to explore a possible connection between antimicrobial use and Parkinson’s disease.

“In Parkinson’s disease, several studies have described alterations of gut microbiota composition, and changes in fecal microbiota abundance have been found to be associated with gastrointestinal and motor symptoms,” they wrote.

Commenting on the delay between the exposure and diagnosis for the most strongly associated antimicrobials, the authors noted that this 10-15 year lag was comparable with what has been found between the peripheral initiation of Parkinson’s disease and its motor manifestation.

“This would also explain the lack of association between antibiotic exposure 1-5 years before index date – if antibiotic exposure could induce or contribute to the pathogenesis of Parkinson’s disease in the gastrointestinal tract, it would probably take several years before the clinical manifestation of Parkinson’s disease,” they wrote.

With regards to the association seen for sulfonamides and trimethoprim – which was 1-5 years before the index date – they speculated this could reflect treatment for urinary tract infections, which individuals with Parkinson’s disease might be more susceptible to in the prodromal phase of the disease.

The authors noted that infectious disease has also been associated with Parkinson’s disease, and that their analysis did not include information about why the antimicrobial agents were prescribed. However, they pointed out that the associations were only for certain antibiotic classes, which makes it unlikely that the association was related to greater burden of infectious disease among individuals with Parkinson’s disease.

The pattern of associations supports the hypothesis that effects on gut microbiota could link antibiotics to Parkinson’s disease. “The link between antibiotic exposure and Parkinson’s disease fits the current view that in a significant proportion of patients the pathology of Parkinson’s disease may originate in the gut, possibly related to microbial changes, years before the onset of typical Parkinson’s disease motor symptoms such as slowness, muscle stiffness, and shaking of the extremities. It was known that bacterial composition of the intestine in patients with Parkinson’s disease is abnormal, but the cause is unclear. Our results suggest that some commonly used antibiotics, which are known to strongly influence the gut microbiota, could be a predisposing factor,” said lead investigator Filip Scheperjans, MD, PhD, from the department of neurology at Helsinki University Hospital.

The findings may have implications for antibiotic prescribing practices in the future, said Dr. Scheperjans. “In addition to the problem of antibiotic resistance, antimicrobial prescribing should also take into account their potentially long-lasting effects on the gut microbiome and the development of certain diseases.”

The study was funded by the Finnish Parkinson Foundation, the Finnish Medical Foundation, the Maire Taponen Foundation, and the Academy of Finland. One author declared relevant patents and his position as founder and chief executive of a private company. No other conflicts of interest were declared.

SOURCE: Mertsalmi TH et al. Mov Disord. 2019 Nov 18. doi: 10.1002/mds.27924.

Certain types of oral antibiotics seem to be associated with an elevated risk of Parkinson’s disease with a delay that is consistent with the proposed duration of a prodromal period, according to a report published in Movement Disorders. Associations were found for broad-spectrum antibiotics and those that act against anaerobic bacteria and fungi. The timing of antibiotic exposure also seemed to matter.

In a nationwide case-control study, Finnish researchers compared data on antibiotic use in 13,976 individuals diagnosed with Parkinson’s disease between 1998 and 2014 with antibiotic-use data from 40,697 controls. The strongest connection with Parkinson’s disease risk was found for oral exposure to macrolides and lincosamides (adjusted odds ratio up to 1.416). After correction for multiple comparisons, exposure to antianaerobics and tetracyclines 10-15 years before the index date, and antifungal medications 1-5 years before the index date were positively associated with Parkinson’s disease risk. In post hoc analyses, further positive associations were found for broad-spectrum antibiotics.

Tuomas H. Mertsalmi, MD, from the Helsinki University Hospital and coauthors reported that this was the first study to explore a possible connection between antimicrobial use and Parkinson’s disease.

“In Parkinson’s disease, several studies have described alterations of gut microbiota composition, and changes in fecal microbiota abundance have been found to be associated with gastrointestinal and motor symptoms,” they wrote.

Commenting on the delay between the exposure and diagnosis for the most strongly associated antimicrobials, the authors noted that this 10-15 year lag was comparable with what has been found between the peripheral initiation of Parkinson’s disease and its motor manifestation.

“This would also explain the lack of association between antibiotic exposure 1-5 years before index date – if antibiotic exposure could induce or contribute to the pathogenesis of Parkinson’s disease in the gastrointestinal tract, it would probably take several years before the clinical manifestation of Parkinson’s disease,” they wrote.

With regards to the association seen for sulfonamides and trimethoprim – which was 1-5 years before the index date – they speculated this could reflect treatment for urinary tract infections, which individuals with Parkinson’s disease might be more susceptible to in the prodromal phase of the disease.

The authors noted that infectious disease has also been associated with Parkinson’s disease, and that their analysis did not include information about why the antimicrobial agents were prescribed. However, they pointed out that the associations were only for certain antibiotic classes, which makes it unlikely that the association was related to greater burden of infectious disease among individuals with Parkinson’s disease.

The pattern of associations supports the hypothesis that effects on gut microbiota could link antibiotics to Parkinson’s disease. “The link between antibiotic exposure and Parkinson’s disease fits the current view that in a significant proportion of patients the pathology of Parkinson’s disease may originate in the gut, possibly related to microbial changes, years before the onset of typical Parkinson’s disease motor symptoms such as slowness, muscle stiffness, and shaking of the extremities. It was known that bacterial composition of the intestine in patients with Parkinson’s disease is abnormal, but the cause is unclear. Our results suggest that some commonly used antibiotics, which are known to strongly influence the gut microbiota, could be a predisposing factor,” said lead investigator Filip Scheperjans, MD, PhD, from the department of neurology at Helsinki University Hospital.

The findings may have implications for antibiotic prescribing practices in the future, said Dr. Scheperjans. “In addition to the problem of antibiotic resistance, antimicrobial prescribing should also take into account their potentially long-lasting effects on the gut microbiome and the development of certain diseases.”

The study was funded by the Finnish Parkinson Foundation, the Finnish Medical Foundation, the Maire Taponen Foundation, and the Academy of Finland. One author declared relevant patents and his position as founder and chief executive of a private company. No other conflicts of interest were declared.

SOURCE: Mertsalmi TH et al. Mov Disord. 2019 Nov 18. doi: 10.1002/mds.27924.

Certain types of oral antibiotics seem to be associated with an elevated risk of Parkinson’s disease with a delay that is consistent with the proposed duration of a prodromal period, according to a report published in Movement Disorders. Associations were found for broad-spectrum antibiotics and those that act against anaerobic bacteria and fungi. The timing of antibiotic exposure also seemed to matter.

In a nationwide case-control study, Finnish researchers compared data on antibiotic use in 13,976 individuals diagnosed with Parkinson’s disease between 1998 and 2014 with antibiotic-use data from 40,697 controls. The strongest connection with Parkinson’s disease risk was found for oral exposure to macrolides and lincosamides (adjusted odds ratio up to 1.416). After correction for multiple comparisons, exposure to antianaerobics and tetracyclines 10-15 years before the index date, and antifungal medications 1-5 years before the index date were positively associated with Parkinson’s disease risk. In post hoc analyses, further positive associations were found for broad-spectrum antibiotics.

Tuomas H. Mertsalmi, MD, from the Helsinki University Hospital and coauthors reported that this was the first study to explore a possible connection between antimicrobial use and Parkinson’s disease.

“In Parkinson’s disease, several studies have described alterations of gut microbiota composition, and changes in fecal microbiota abundance have been found to be associated with gastrointestinal and motor symptoms,” they wrote.

Commenting on the delay between the exposure and diagnosis for the most strongly associated antimicrobials, the authors noted that this 10-15 year lag was comparable with what has been found between the peripheral initiation of Parkinson’s disease and its motor manifestation.

“This would also explain the lack of association between antibiotic exposure 1-5 years before index date – if antibiotic exposure could induce or contribute to the pathogenesis of Parkinson’s disease in the gastrointestinal tract, it would probably take several years before the clinical manifestation of Parkinson’s disease,” they wrote.

With regards to the association seen for sulfonamides and trimethoprim – which was 1-5 years before the index date – they speculated this could reflect treatment for urinary tract infections, which individuals with Parkinson’s disease might be more susceptible to in the prodromal phase of the disease.

The authors noted that infectious disease has also been associated with Parkinson’s disease, and that their analysis did not include information about why the antimicrobial agents were prescribed. However, they pointed out that the associations were only for certain antibiotic classes, which makes it unlikely that the association was related to greater burden of infectious disease among individuals with Parkinson’s disease.

The pattern of associations supports the hypothesis that effects on gut microbiota could link antibiotics to Parkinson’s disease. “The link between antibiotic exposure and Parkinson’s disease fits the current view that in a significant proportion of patients the pathology of Parkinson’s disease may originate in the gut, possibly related to microbial changes, years before the onset of typical Parkinson’s disease motor symptoms such as slowness, muscle stiffness, and shaking of the extremities. It was known that bacterial composition of the intestine in patients with Parkinson’s disease is abnormal, but the cause is unclear. Our results suggest that some commonly used antibiotics, which are known to strongly influence the gut microbiota, could be a predisposing factor,” said lead investigator Filip Scheperjans, MD, PhD, from the department of neurology at Helsinki University Hospital.

The findings may have implications for antibiotic prescribing practices in the future, said Dr. Scheperjans. “In addition to the problem of antibiotic resistance, antimicrobial prescribing should also take into account their potentially long-lasting effects on the gut microbiome and the development of certain diseases.”

The study was funded by the Finnish Parkinson Foundation, the Finnish Medical Foundation, the Maire Taponen Foundation, and the Academy of Finland. One author declared relevant patents and his position as founder and chief executive of a private company. No other conflicts of interest were declared.

SOURCE: Mertsalmi TH et al. Mov Disord. 2019 Nov 18. doi: 10.1002/mds.27924.

Several potential biomarkers may indicate whether patients with bipolar disorder may have high-recurrence disease with a cycle length that progressively shortens, according to Erik Smedler, MD, PhD, of the department of psychiatry and neurochemistry at Gothenburg (Sweden) University.

For the analysis, published in European Neuropsychopharmacology, Dr. Smedler and fellow investigators recruited 3,074 patients from the Swedish Bipolar Collection between 2009 and 2013 who had at least two inpatient episodes separated by at least 8 weeks. A total of 745 patients had serum samples available; assays for 203 different protein biomarkers were performed on those samples.

The investigators clustered patients according to frequency – with low-frequency recurrence defined as a maximum of one inpatient episode per year – and by cycle length – with sensitized patients having progressively shorter periods between inpatient episodes. No difference in biomarkers or clinical features were seen between high- and low-frequency recurrence patients, but sensitized patients were significantly more ill and were more likely to be treated with antidepressants.

In addition, in a specific cohort of patients who were both sensitized and had a high recurrence rate (at least five inpatient episodes), four proteins were expressed at a significantly lower level than that of nonsensitized patients: tumor necrosis factor receptor-2, tumor necrosis factor receptor superfamily member 4, placenta growth factor, and adrenomedullin. Sensitization also was associated with a single nucleotide polymorphism near the calcium channel gene CACNA2D3.

“These results suggest the potential for translational research aimed at preventive actions,” the investigators wrote.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Smedler E et al. Eur Neuropsychopharmacol. 2019 Aug 1. doi: 10.1016/j.euroneuro.2019.07.132.

Several potential biomarkers may indicate whether patients with bipolar disorder may have high-recurrence disease with a cycle length that progressively shortens, according to Erik Smedler, MD, PhD, of the department of psychiatry and neurochemistry at Gothenburg (Sweden) University.

For the analysis, published in European Neuropsychopharmacology, Dr. Smedler and fellow investigators recruited 3,074 patients from the Swedish Bipolar Collection between 2009 and 2013 who had at least two inpatient episodes separated by at least 8 weeks. A total of 745 patients had serum samples available; assays for 203 different protein biomarkers were performed on those samples.

The investigators clustered patients according to frequency – with low-frequency recurrence defined as a maximum of one inpatient episode per year – and by cycle length – with sensitized patients having progressively shorter periods between inpatient episodes. No difference in biomarkers or clinical features were seen between high- and low-frequency recurrence patients, but sensitized patients were significantly more ill and were more likely to be treated with antidepressants.

In addition, in a specific cohort of patients who were both sensitized and had a high recurrence rate (at least five inpatient episodes), four proteins were expressed at a significantly lower level than that of nonsensitized patients: tumor necrosis factor receptor-2, tumor necrosis factor receptor superfamily member 4, placenta growth factor, and adrenomedullin. Sensitization also was associated with a single nucleotide polymorphism near the calcium channel gene CACNA2D3.

“These results suggest the potential for translational research aimed at preventive actions,” the investigators wrote.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Smedler E et al. Eur Neuropsychopharmacol. 2019 Aug 1. doi: 10.1016/j.euroneuro.2019.07.132.

Several potential biomarkers may indicate whether patients with bipolar disorder may have high-recurrence disease with a cycle length that progressively shortens, according to Erik Smedler, MD, PhD, of the department of psychiatry and neurochemistry at Gothenburg (Sweden) University.

For the analysis, published in European Neuropsychopharmacology, Dr. Smedler and fellow investigators recruited 3,074 patients from the Swedish Bipolar Collection between 2009 and 2013 who had at least two inpatient episodes separated by at least 8 weeks. A total of 745 patients had serum samples available; assays for 203 different protein biomarkers were performed on those samples.

The investigators clustered patients according to frequency – with low-frequency recurrence defined as a maximum of one inpatient episode per year – and by cycle length – with sensitized patients having progressively shorter periods between inpatient episodes. No difference in biomarkers or clinical features were seen between high- and low-frequency recurrence patients, but sensitized patients were significantly more ill and were more likely to be treated with antidepressants.

In addition, in a specific cohort of patients who were both sensitized and had a high recurrence rate (at least five inpatient episodes), four proteins were expressed at a significantly lower level than that of nonsensitized patients: tumor necrosis factor receptor-2, tumor necrosis factor receptor superfamily member 4, placenta growth factor, and adrenomedullin. Sensitization also was associated with a single nucleotide polymorphism near the calcium channel gene CACNA2D3.

“These results suggest the potential for translational research aimed at preventive actions,” the investigators wrote.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Smedler E et al. Eur Neuropsychopharmacol. 2019 Aug 1. doi: 10.1016/j.euroneuro.2019.07.132.