Literature Review

A new study provides more evidence that sildenafil (Viagra), which is used to treat erectile dsysfuntion (ED), may help protect against Alzheimer’s disease.

The large real-world analysis of patient data from two databases showed a 30%-54% reduced prevalence in Alzheimer’s disease among patients who took sildenafil (Viagra) than those who did not, after adjusting for potential confounding factors.

This observation was further supported by mechanistic studies showing decreased neurotoxic protein levels in brain cells exposed to the phosphodiesterase type 5 inhibitor (PDE5i).

“Our findings provide further weight to repurposing this existing FDA-approved drug as a novel treatment for Alzheimer’s, which is in great need of new therapies,” Feixiong Cheng, PhD, director of the Cleveland Clinic Genome Center, who led the research, said in a news release. 

“We used artificial intelligence to integrate data across multiple domains which all indicated sildenafil’s potential against this devastating neurological disease,” Dr. Cheng noted. 

The study was published online in the Journal of Alzheimer’s Disease.
 

Neuroprotective?

Using real-world patient data from the MarketScan Medicare Supplemental database (2012-2017) and the Clinformatics database (2007-2020), the researchers conducted propensity score-stratified analyses after adjusting for gender, age, race, and comorbidities. 

They searched for all individuals with pharmacy claims for sildenafil or four comparator drugs — bumetanide, furosemide, spironolactone, and nifedipine. Results showed that sildenafil use was associated with reduced likelihood of Alzheimer’s disease relative to the control drugs. 

For example, sildenafil use was associated with a 54% reduced incidence of Alzheimer’s disease in MarketScan (hazard ratio [HR], 0.46; 95% CI, 0.32-0.66) and a 30% reduced prevalence of Alzheimer’s disease in Clinformatics (HR, 0.70; 95% CI, 0.49-1.00) compared with spironolactone.

The findings support a study published earlier this year that found a potential protective effect of PDE5i treatment on Alzheimer’s disease risk.

However, this research and the current study are contradicted by another paper published in Brain Communications in late 2022 which showed no such link between ED meds and reduced Alzheimer’s disease risk.

The investigators also found that sildenafil reduces tau hyperphosphorylation (pTau181 and pTau205) in a dose-dependent manner in both familial and sporadic Alzheimer’s disease patient induced pluripotent stem cell (iPSC)-derived neurons. 

They further demonstrated through RNA-sequencing data analysis that sildenafil specifically targets Alzheimer’s disease related genes and pathobiological pathways, mechanistically supporting the beneficial effect of sildenafil in Alzheimer’s disease.

“We believe our findings provide the evidence needed for clinical trials to further examine the potential effectiveness of sildenafil in patients with Alzheimer’s disease,” Dr. Cheng said. 

The study was primarily supported by the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS). Dr. Cheng had no relevant disclosures. 

A version of this article appeared on Medscape.com.

A new study provides more evidence that sildenafil (Viagra), which is used to treat erectile dsysfuntion (ED), may help protect against Alzheimer’s disease.

The large real-world analysis of patient data from two databases showed a 30%-54% reduced prevalence in Alzheimer’s disease among patients who took sildenafil (Viagra) than those who did not, after adjusting for potential confounding factors.

This observation was further supported by mechanistic studies showing decreased neurotoxic protein levels in brain cells exposed to the phosphodiesterase type 5 inhibitor (PDE5i).

“Our findings provide further weight to repurposing this existing FDA-approved drug as a novel treatment for Alzheimer’s, which is in great need of new therapies,” Feixiong Cheng, PhD, director of the Cleveland Clinic Genome Center, who led the research, said in a news release. 

“We used artificial intelligence to integrate data across multiple domains which all indicated sildenafil’s potential against this devastating neurological disease,” Dr. Cheng noted. 

The study was published online in the Journal of Alzheimer’s Disease.
 

Neuroprotective?

Using real-world patient data from the MarketScan Medicare Supplemental database (2012-2017) and the Clinformatics database (2007-2020), the researchers conducted propensity score-stratified analyses after adjusting for gender, age, race, and comorbidities. 

They searched for all individuals with pharmacy claims for sildenafil or four comparator drugs — bumetanide, furosemide, spironolactone, and nifedipine. Results showed that sildenafil use was associated with reduced likelihood of Alzheimer’s disease relative to the control drugs. 

For example, sildenafil use was associated with a 54% reduced incidence of Alzheimer’s disease in MarketScan (hazard ratio [HR], 0.46; 95% CI, 0.32-0.66) and a 30% reduced prevalence of Alzheimer’s disease in Clinformatics (HR, 0.70; 95% CI, 0.49-1.00) compared with spironolactone.

The findings support a study published earlier this year that found a potential protective effect of PDE5i treatment on Alzheimer’s disease risk.

However, this research and the current study are contradicted by another paper published in Brain Communications in late 2022 which showed no such link between ED meds and reduced Alzheimer’s disease risk.

The investigators also found that sildenafil reduces tau hyperphosphorylation (pTau181 and pTau205) in a dose-dependent manner in both familial and sporadic Alzheimer’s disease patient induced pluripotent stem cell (iPSC)-derived neurons. 

They further demonstrated through RNA-sequencing data analysis that sildenafil specifically targets Alzheimer’s disease related genes and pathobiological pathways, mechanistically supporting the beneficial effect of sildenafil in Alzheimer’s disease.

“We believe our findings provide the evidence needed for clinical trials to further examine the potential effectiveness of sildenafil in patients with Alzheimer’s disease,” Dr. Cheng said. 

The study was primarily supported by the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS). Dr. Cheng had no relevant disclosures. 

A version of this article appeared on Medscape.com.

A new study provides more evidence that sildenafil (Viagra), which is used to treat erectile dsysfuntion (ED), may help protect against Alzheimer’s disease.

The large real-world analysis of patient data from two databases showed a 30%-54% reduced prevalence in Alzheimer’s disease among patients who took sildenafil (Viagra) than those who did not, after adjusting for potential confounding factors.

This observation was further supported by mechanistic studies showing decreased neurotoxic protein levels in brain cells exposed to the phosphodiesterase type 5 inhibitor (PDE5i).

“Our findings provide further weight to repurposing this existing FDA-approved drug as a novel treatment for Alzheimer’s, which is in great need of new therapies,” Feixiong Cheng, PhD, director of the Cleveland Clinic Genome Center, who led the research, said in a news release. 

“We used artificial intelligence to integrate data across multiple domains which all indicated sildenafil’s potential against this devastating neurological disease,” Dr. Cheng noted. 

The study was published online in the Journal of Alzheimer’s Disease.
 

Neuroprotective?

Using real-world patient data from the MarketScan Medicare Supplemental database (2012-2017) and the Clinformatics database (2007-2020), the researchers conducted propensity score-stratified analyses after adjusting for gender, age, race, and comorbidities. 

They searched for all individuals with pharmacy claims for sildenafil or four comparator drugs — bumetanide, furosemide, spironolactone, and nifedipine. Results showed that sildenafil use was associated with reduced likelihood of Alzheimer’s disease relative to the control drugs. 

For example, sildenafil use was associated with a 54% reduced incidence of Alzheimer’s disease in MarketScan (hazard ratio [HR], 0.46; 95% CI, 0.32-0.66) and a 30% reduced prevalence of Alzheimer’s disease in Clinformatics (HR, 0.70; 95% CI, 0.49-1.00) compared with spironolactone.

The findings support a study published earlier this year that found a potential protective effect of PDE5i treatment on Alzheimer’s disease risk.

However, this research and the current study are contradicted by another paper published in Brain Communications in late 2022 which showed no such link between ED meds and reduced Alzheimer’s disease risk.

The investigators also found that sildenafil reduces tau hyperphosphorylation (pTau181 and pTau205) in a dose-dependent manner in both familial and sporadic Alzheimer’s disease patient induced pluripotent stem cell (iPSC)-derived neurons. 

They further demonstrated through RNA-sequencing data analysis that sildenafil specifically targets Alzheimer’s disease related genes and pathobiological pathways, mechanistically supporting the beneficial effect of sildenafil in Alzheimer’s disease.

“We believe our findings provide the evidence needed for clinical trials to further examine the potential effectiveness of sildenafil in patients with Alzheimer’s disease,” Dr. Cheng said. 

The study was primarily supported by the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS). Dr. Cheng had no relevant disclosures. 

A version of this article appeared on Medscape.com.

Frexalimab (Sanofi), a novel, investigational second-generation inhibitor of the CD40 ligand, significantly reduced disease activity in relapsing multiple sclerosis (MS) and was well tolerated in a phase 2 study.

At week 12, there was an 89% reduction in new gadolinium (Gd)-enhancing T1 brain lesions — a standard measure of active inflammation in MS – in the high-dose frexalimab group and a 79% reduction in the low-dose treatment group compared with placebo, meeting the study’s primary endpoint.

The effects of frexalimab were sustained over time, “especially at the high dose of frexalimab where 96% of patients were free of new active lesions after 24 weeks of treatment,” first author Patrick Vermersch, MD, PhD, University of Lille, CHU Lille, France, said in a news release.

The full results were published online on in The New England Journal of Medicine, following presentation of preliminary data at the Consortium of Multiple Sclerosis Centers 2023 Annual Meeting.
 

‘Unambiguous Benefit’

Frexalimab blocks the costimulatory CD40/CD40L pathway, which regulates both adaptive and innate immune responses, and has been implicated in the pathogenesis of MS.

“Through this unique upstream mechanism of action, frexalimab has the potential to address both acute and chronic neuroinflammation in MS, without causing lymphocyte depletion,” a Sanofi press statement noted.

The phase 2 study enrolled 129 adults (mean age, 36 years; 66% women) with relapsing MS, 30% of whom had Gd-enhancing lesions at baseline.

Participants received 1200 mg of frexalimab administered intravenously every 4 weeks (with an 1800-mg loading dose; n = 52), 300 mg of frexalimab administered subcutaneously every 2 weeks (with a 600-mg loading dose; n = 51), or matching placebos for each active treatment (n = 12 and n = 14, respectively).

All but four patients completed the 12-week double-blind period and entered the open-label period.

The primary end point was the number of new Gd-enhancing T1-weighted lesions seen on MRI at week 12 relative to week 8.

At week 12, the adjusted mean number of new Gd-enhancing T1 lesions was 0.2 and 0.3 in the high- and low-dose frexalimab groups, respectively, compared with 1.4 in the pooled placebo group.

The rate ratios, as compared with placebo, were 0.11 in the high-dose group and 0.21 in the low-dose group, corresponding to 89% and 79% reductions in the high- and low-dose groups, respectively.

On the secondary endpoint of number of new/enlarging T2-weighted lesions at week 12, rate ratios in the high- and low-dose groups were 0.08 and 0.14, respectively, corresponding to 92% and 86% reduction in the high- and low-dose treatment groups vs placebo.

The effects were sustained over time across both active treatment groups.

Frexalimab also lowered plasma levels of neurofilament light chain, a biomarker of neuroaxonal damage in MS, as well as plasma levels of CXCL13, a biomarker of inflammatory activity.
 

Phase 3 Trials Underway

The authors noted that the trial was too brief and small to draw conclusions regarding clinical outcomes. However, during the 12-week double-blind period, no relapses occurred in the high-dose frexalimab group, whereas relapses occurred in roughly 4% of those in the low-dose frexalimab group and the pooled placebo group.

There was no change from baseline to 12 weeks in median scores on the Expanded Disability Status Scale in any study group.

No serious or severe adverse events or deaths were reported during the double-blind period. There were no thromboembolic events — a concern with first-generation anti–CD40L antibodies.

Depletion of lymphocytes was not observed. More infections were observed with frexalimab than with placebo, but no serious infections occurred during 24 weeks of frexalimab treatment. The most common adverse events were COVID-19 and headache. All cases of COVID-19 were uncomplicated and mild to moderate in severity.

Bolstered by the promising phase 2 data, Sanofi has initiated two phase 3 studies assessing frexalimab in relapsing MS and non-relapsing secondary progressive MS.
 

‘A High Bar for Any New Treatment’

In an accompanying editorial, Stephen L. Hauser, MD, with UCSF Weill Institute for Neurosciences, San Francisco, California, wrote that the results “appear clear, although the clinical significance is uncertain — clear because there was an unambiguous benefit with regard to short-term MRI outcomes in patients who received frexalimab as compared with those who received placebo and because a generally low level of MRI activity persisted during an additional 12-week open-label extension period.”

If the findings hold with longer-term use, Dr. Hauser continued, “it seems likely that there will be a protective effect of frexalimab therapy with regard to relapses of multiple sclerosis.”

Dr. Hauser noted, however, that the “striking clinical benefits and safety profile of the available high-efficacy therapies for relapsing multiple sclerosis create a high bar for any new treatment.”

“In this trial, the MRI outcomes with frexalimab therapy were impressive but appear to be less complete than those with anti-CD20 agents, although trials of different agents cannot be directly compared.”

“Even if future studies show frexalimab to be competitive with currently available therapies for relapsing multiple sclerosis, the paramount need is for more effective therapy against progression,” Dr. Hauser wrote.

While the current trial was neither designed nor powered to assess benefits against progressive MS, “progression is where the true clinical value of frexalimab, and its place in the therapeutic armamentarium against multiple sclerosis, will need to be defined,” Dr. Hauser concluded.

The study was supported by Sanofi. Disclosures for authors and editorialist are available at NEJM.org.
 

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

Frexalimab (Sanofi), a novel, investigational second-generation inhibitor of the CD40 ligand, significantly reduced disease activity in relapsing multiple sclerosis (MS) and was well tolerated in a phase 2 study.

At week 12, there was an 89% reduction in new gadolinium (Gd)-enhancing T1 brain lesions — a standard measure of active inflammation in MS – in the high-dose frexalimab group and a 79% reduction in the low-dose treatment group compared with placebo, meeting the study’s primary endpoint.

The effects of frexalimab were sustained over time, “especially at the high dose of frexalimab where 96% of patients were free of new active lesions after 24 weeks of treatment,” first author Patrick Vermersch, MD, PhD, University of Lille, CHU Lille, France, said in a news release.

The full results were published online on in The New England Journal of Medicine, following presentation of preliminary data at the Consortium of Multiple Sclerosis Centers 2023 Annual Meeting.
 

‘Unambiguous Benefit’

Frexalimab blocks the costimulatory CD40/CD40L pathway, which regulates both adaptive and innate immune responses, and has been implicated in the pathogenesis of MS.

“Through this unique upstream mechanism of action, frexalimab has the potential to address both acute and chronic neuroinflammation in MS, without causing lymphocyte depletion,” a Sanofi press statement noted.

The phase 2 study enrolled 129 adults (mean age, 36 years; 66% women) with relapsing MS, 30% of whom had Gd-enhancing lesions at baseline.

Participants received 1200 mg of frexalimab administered intravenously every 4 weeks (with an 1800-mg loading dose; n = 52), 300 mg of frexalimab administered subcutaneously every 2 weeks (with a 600-mg loading dose; n = 51), or matching placebos for each active treatment (n = 12 and n = 14, respectively).

All but four patients completed the 12-week double-blind period and entered the open-label period.

The primary end point was the number of new Gd-enhancing T1-weighted lesions seen on MRI at week 12 relative to week 8.

At week 12, the adjusted mean number of new Gd-enhancing T1 lesions was 0.2 and 0.3 in the high- and low-dose frexalimab groups, respectively, compared with 1.4 in the pooled placebo group.

The rate ratios, as compared with placebo, were 0.11 in the high-dose group and 0.21 in the low-dose group, corresponding to 89% and 79% reductions in the high- and low-dose groups, respectively.

On the secondary endpoint of number of new/enlarging T2-weighted lesions at week 12, rate ratios in the high- and low-dose groups were 0.08 and 0.14, respectively, corresponding to 92% and 86% reduction in the high- and low-dose treatment groups vs placebo.

The effects were sustained over time across both active treatment groups.

Frexalimab also lowered plasma levels of neurofilament light chain, a biomarker of neuroaxonal damage in MS, as well as plasma levels of CXCL13, a biomarker of inflammatory activity.
 

Phase 3 Trials Underway

The authors noted that the trial was too brief and small to draw conclusions regarding clinical outcomes. However, during the 12-week double-blind period, no relapses occurred in the high-dose frexalimab group, whereas relapses occurred in roughly 4% of those in the low-dose frexalimab group and the pooled placebo group.

There was no change from baseline to 12 weeks in median scores on the Expanded Disability Status Scale in any study group.

No serious or severe adverse events or deaths were reported during the double-blind period. There were no thromboembolic events — a concern with first-generation anti–CD40L antibodies.

Depletion of lymphocytes was not observed. More infections were observed with frexalimab than with placebo, but no serious infections occurred during 24 weeks of frexalimab treatment. The most common adverse events were COVID-19 and headache. All cases of COVID-19 were uncomplicated and mild to moderate in severity.

Bolstered by the promising phase 2 data, Sanofi has initiated two phase 3 studies assessing frexalimab in relapsing MS and non-relapsing secondary progressive MS.
 

‘A High Bar for Any New Treatment’

In an accompanying editorial, Stephen L. Hauser, MD, with UCSF Weill Institute for Neurosciences, San Francisco, California, wrote that the results “appear clear, although the clinical significance is uncertain — clear because there was an unambiguous benefit with regard to short-term MRI outcomes in patients who received frexalimab as compared with those who received placebo and because a generally low level of MRI activity persisted during an additional 12-week open-label extension period.”

If the findings hold with longer-term use, Dr. Hauser continued, “it seems likely that there will be a protective effect of frexalimab therapy with regard to relapses of multiple sclerosis.”

Dr. Hauser noted, however, that the “striking clinical benefits and safety profile of the available high-efficacy therapies for relapsing multiple sclerosis create a high bar for any new treatment.”

“In this trial, the MRI outcomes with frexalimab therapy were impressive but appear to be less complete than those with anti-CD20 agents, although trials of different agents cannot be directly compared.”

“Even if future studies show frexalimab to be competitive with currently available therapies for relapsing multiple sclerosis, the paramount need is for more effective therapy against progression,” Dr. Hauser wrote.

While the current trial was neither designed nor powered to assess benefits against progressive MS, “progression is where the true clinical value of frexalimab, and its place in the therapeutic armamentarium against multiple sclerosis, will need to be defined,” Dr. Hauser concluded.

The study was supported by Sanofi. Disclosures for authors and editorialist are available at NEJM.org.
 

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

Frexalimab (Sanofi), a novel, investigational second-generation inhibitor of the CD40 ligand, significantly reduced disease activity in relapsing multiple sclerosis (MS) and was well tolerated in a phase 2 study.

At week 12, there was an 89% reduction in new gadolinium (Gd)-enhancing T1 brain lesions — a standard measure of active inflammation in MS – in the high-dose frexalimab group and a 79% reduction in the low-dose treatment group compared with placebo, meeting the study’s primary endpoint.

The effects of frexalimab were sustained over time, “especially at the high dose of frexalimab where 96% of patients were free of new active lesions after 24 weeks of treatment,” first author Patrick Vermersch, MD, PhD, University of Lille, CHU Lille, France, said in a news release.

The full results were published online on in The New England Journal of Medicine, following presentation of preliminary data at the Consortium of Multiple Sclerosis Centers 2023 Annual Meeting.
 

‘Unambiguous Benefit’

Frexalimab blocks the costimulatory CD40/CD40L pathway, which regulates both adaptive and innate immune responses, and has been implicated in the pathogenesis of MS.

“Through this unique upstream mechanism of action, frexalimab has the potential to address both acute and chronic neuroinflammation in MS, without causing lymphocyte depletion,” a Sanofi press statement noted.

The phase 2 study enrolled 129 adults (mean age, 36 years; 66% women) with relapsing MS, 30% of whom had Gd-enhancing lesions at baseline.

Participants received 1200 mg of frexalimab administered intravenously every 4 weeks (with an 1800-mg loading dose; n = 52), 300 mg of frexalimab administered subcutaneously every 2 weeks (with a 600-mg loading dose; n = 51), or matching placebos for each active treatment (n = 12 and n = 14, respectively).

All but four patients completed the 12-week double-blind period and entered the open-label period.

The primary end point was the number of new Gd-enhancing T1-weighted lesions seen on MRI at week 12 relative to week 8.

At week 12, the adjusted mean number of new Gd-enhancing T1 lesions was 0.2 and 0.3 in the high- and low-dose frexalimab groups, respectively, compared with 1.4 in the pooled placebo group.

The rate ratios, as compared with placebo, were 0.11 in the high-dose group and 0.21 in the low-dose group, corresponding to 89% and 79% reductions in the high- and low-dose groups, respectively.

On the secondary endpoint of number of new/enlarging T2-weighted lesions at week 12, rate ratios in the high- and low-dose groups were 0.08 and 0.14, respectively, corresponding to 92% and 86% reduction in the high- and low-dose treatment groups vs placebo.

The effects were sustained over time across both active treatment groups.

Frexalimab also lowered plasma levels of neurofilament light chain, a biomarker of neuroaxonal damage in MS, as well as plasma levels of CXCL13, a biomarker of inflammatory activity.
 

Phase 3 Trials Underway

The authors noted that the trial was too brief and small to draw conclusions regarding clinical outcomes. However, during the 12-week double-blind period, no relapses occurred in the high-dose frexalimab group, whereas relapses occurred in roughly 4% of those in the low-dose frexalimab group and the pooled placebo group.

There was no change from baseline to 12 weeks in median scores on the Expanded Disability Status Scale in any study group.

No serious or severe adverse events or deaths were reported during the double-blind period. There were no thromboembolic events — a concern with first-generation anti–CD40L antibodies.

Depletion of lymphocytes was not observed. More infections were observed with frexalimab than with placebo, but no serious infections occurred during 24 weeks of frexalimab treatment. The most common adverse events were COVID-19 and headache. All cases of COVID-19 were uncomplicated and mild to moderate in severity.

Bolstered by the promising phase 2 data, Sanofi has initiated two phase 3 studies assessing frexalimab in relapsing MS and non-relapsing secondary progressive MS.
 

‘A High Bar for Any New Treatment’

In an accompanying editorial, Stephen L. Hauser, MD, with UCSF Weill Institute for Neurosciences, San Francisco, California, wrote that the results “appear clear, although the clinical significance is uncertain — clear because there was an unambiguous benefit with regard to short-term MRI outcomes in patients who received frexalimab as compared with those who received placebo and because a generally low level of MRI activity persisted during an additional 12-week open-label extension period.”

If the findings hold with longer-term use, Dr. Hauser continued, “it seems likely that there will be a protective effect of frexalimab therapy with regard to relapses of multiple sclerosis.”

Dr. Hauser noted, however, that the “striking clinical benefits and safety profile of the available high-efficacy therapies for relapsing multiple sclerosis create a high bar for any new treatment.”

“In this trial, the MRI outcomes with frexalimab therapy were impressive but appear to be less complete than those with anti-CD20 agents, although trials of different agents cannot be directly compared.”

“Even if future studies show frexalimab to be competitive with currently available therapies for relapsing multiple sclerosis, the paramount need is for more effective therapy against progression,” Dr. Hauser wrote.

While the current trial was neither designed nor powered to assess benefits against progressive MS, “progression is where the true clinical value of frexalimab, and its place in the therapeutic armamentarium against multiple sclerosis, will need to be defined,” Dr. Hauser concluded.

The study was supported by Sanofi. Disclosures for authors and editorialist are available at NEJM.org.
 

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

TOPLINE:

Patients with multiple sclerosis (MS) have almost double the risk for seizures, with the risk even greater with sphingosine-1-phosphate receptor (S1PR) modulators, results of a new meta-analysis of randomized controlled trials (RCTs) suggest. Those with a progressive disease phenotype are at particularly high seizure risk.

METHODOLOGY:

• The meta-analysis included 63 phase 3 RCTs with 53,535 patients.
• Most of the studies included in the meta-analysis investigated disease-modifying treatments compared with placebo or an active comparator such as interferon beta, teriflunomide, and dimethyl fumarate, in terms of relapse rate and/or disability progression.
• Researchers extracted relevant information from studies, including MS subtype (clinically isolated syndrome, relapsing-remitting, primary progressive, or secondary progressive MS), mean Expanded Disability Status Scale (EDSS) score, lesion volume on T2-hyperintense sequence, normalized brain volume, and number of seizures or epilepsy events.
• They calculated the pooled effect size of studies on the incidence rate of seizure or epilepsy as the number of events per patient-years and explored which variables influenced the pooled effect size.

TAKEAWAY:

• A total of 120 patients experienced epileptic seizure events over a median follow-up of 2 years, resulting in a pooled incidence rate of 68.0 (95% CI, 49.1-86.9) per 100,000 patient-years, which investigators noted is significantly higher than the general population rate of 34.6.
• Higher seizure incidence rates were found among patients with progressive disease courses, longer time since clinical onset, higher EDSS scores, and lower normalized brain volume; age and T2 lesion volume did not affect the pooled effect size.
• Patients treated with S1PR modulators (fingolimod, ozanimod, ponesimod, and siponimod) had more than double the risk for seizure compared with placebo or comparators (estimated incident seizure risk ratio, 2.45; P = .008).

IN PRACTICE:

“Our findings underscore epilepsy as a significant comorbidity in MS and emphasize the necessity for further research into its triggers, preventive measures and treatment strategies,” the authors wrote.

SOURCE:

The study, led by Valeria Pozzilli, Unit of Neurology, Neurophysiology and Neurobiology, Department of Medicine and Surgery, Campus Bio-Medico University, Roma, Italy, was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.

LIMITATIONS:

As none of the included RCTs considered epilepsy an exclusion criterion, patients with comorbid epilepsy may have been enrolled in these studies. There was significant diversity in reporting of adverse events across studies. While this study’s statistical methodology was robust, the findings can’t be applied directly to individuals due to the risk for ecological fallacy.

DISCLOSURES:

Pozzilli had no relevant conflicts of interests. See paper for disclosures of other authors.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with multiple sclerosis (MS) have almost double the risk for seizures, with the risk even greater with sphingosine-1-phosphate receptor (S1PR) modulators, results of a new meta-analysis of randomized controlled trials (RCTs) suggest. Those with a progressive disease phenotype are at particularly high seizure risk.

METHODOLOGY:

• The meta-analysis included 63 phase 3 RCTs with 53,535 patients.
• Most of the studies included in the meta-analysis investigated disease-modifying treatments compared with placebo or an active comparator such as interferon beta, teriflunomide, and dimethyl fumarate, in terms of relapse rate and/or disability progression.
• Researchers extracted relevant information from studies, including MS subtype (clinically isolated syndrome, relapsing-remitting, primary progressive, or secondary progressive MS), mean Expanded Disability Status Scale (EDSS) score, lesion volume on T2-hyperintense sequence, normalized brain volume, and number of seizures or epilepsy events.
• They calculated the pooled effect size of studies on the incidence rate of seizure or epilepsy as the number of events per patient-years and explored which variables influenced the pooled effect size.

TAKEAWAY:

• A total of 120 patients experienced epileptic seizure events over a median follow-up of 2 years, resulting in a pooled incidence rate of 68.0 (95% CI, 49.1-86.9) per 100,000 patient-years, which investigators noted is significantly higher than the general population rate of 34.6.
• Higher seizure incidence rates were found among patients with progressive disease courses, longer time since clinical onset, higher EDSS scores, and lower normalized brain volume; age and T2 lesion volume did not affect the pooled effect size.
• Patients treated with S1PR modulators (fingolimod, ozanimod, ponesimod, and siponimod) had more than double the risk for seizure compared with placebo or comparators (estimated incident seizure risk ratio, 2.45; P = .008).

IN PRACTICE:

“Our findings underscore epilepsy as a significant comorbidity in MS and emphasize the necessity for further research into its triggers, preventive measures and treatment strategies,” the authors wrote.

SOURCE:

The study, led by Valeria Pozzilli, Unit of Neurology, Neurophysiology and Neurobiology, Department of Medicine and Surgery, Campus Bio-Medico University, Roma, Italy, was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.

LIMITATIONS:

As none of the included RCTs considered epilepsy an exclusion criterion, patients with comorbid epilepsy may have been enrolled in these studies. There was significant diversity in reporting of adverse events across studies. While this study’s statistical methodology was robust, the findings can’t be applied directly to individuals due to the risk for ecological fallacy.

DISCLOSURES:

Pozzilli had no relevant conflicts of interests. See paper for disclosures of other authors.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with multiple sclerosis (MS) have almost double the risk for seizures, with the risk even greater with sphingosine-1-phosphate receptor (S1PR) modulators, results of a new meta-analysis of randomized controlled trials (RCTs) suggest. Those with a progressive disease phenotype are at particularly high seizure risk.

METHODOLOGY:

• The meta-analysis included 63 phase 3 RCTs with 53,535 patients.
• Most of the studies included in the meta-analysis investigated disease-modifying treatments compared with placebo or an active comparator such as interferon beta, teriflunomide, and dimethyl fumarate, in terms of relapse rate and/or disability progression.
• Researchers extracted relevant information from studies, including MS subtype (clinically isolated syndrome, relapsing-remitting, primary progressive, or secondary progressive MS), mean Expanded Disability Status Scale (EDSS) score, lesion volume on T2-hyperintense sequence, normalized brain volume, and number of seizures or epilepsy events.
• They calculated the pooled effect size of studies on the incidence rate of seizure or epilepsy as the number of events per patient-years and explored which variables influenced the pooled effect size.

TAKEAWAY:

• A total of 120 patients experienced epileptic seizure events over a median follow-up of 2 years, resulting in a pooled incidence rate of 68.0 (95% CI, 49.1-86.9) per 100,000 patient-years, which investigators noted is significantly higher than the general population rate of 34.6.
• Higher seizure incidence rates were found among patients with progressive disease courses, longer time since clinical onset, higher EDSS scores, and lower normalized brain volume; age and T2 lesion volume did not affect the pooled effect size.
• Patients treated with S1PR modulators (fingolimod, ozanimod, ponesimod, and siponimod) had more than double the risk for seizure compared with placebo or comparators (estimated incident seizure risk ratio, 2.45; P = .008).

IN PRACTICE:

“Our findings underscore epilepsy as a significant comorbidity in MS and emphasize the necessity for further research into its triggers, preventive measures and treatment strategies,” the authors wrote.

SOURCE:

The study, led by Valeria Pozzilli, Unit of Neurology, Neurophysiology and Neurobiology, Department of Medicine and Surgery, Campus Bio-Medico University, Roma, Italy, was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.

LIMITATIONS:

As none of the included RCTs considered epilepsy an exclusion criterion, patients with comorbid epilepsy may have been enrolled in these studies. There was significant diversity in reporting of adverse events across studies. While this study’s statistical methodology was robust, the findings can’t be applied directly to individuals due to the risk for ecological fallacy.

DISCLOSURES:

Pozzilli had no relevant conflicts of interests. See paper for disclosures of other authors.

A version of this article appeared on Medscape.com.

A study spanning 20 years helps nail down the timing of biomarker changes that occur in the period between normal cognition and a diagnosis of sporadic Alzheimer’s disease, something that hasn’t previously been extensively investigated in longitudinal studies.

By analyzing cerebral spinal fluid (CSF), as well as cognitive and brain imaging assessments conducted every few years for two decades, researchers were able to plot the course of changing levels of amyloid-beta 42 (Abeta42), phosphorylated tau 181 (p-tau181), and neurofilament light chain (NfL) in adults with Alzheimer’s disease and mark when those levels began to deviate from those of adults without Alzheimer’s disease.

Levels of Abeta42 in CSF and the ratio of Abeta42 to Abeta40 in people who developed Alzheimer’s disease diverged from those of peers who remained cognitively normal at 18 years and 14 years, respectively, before clinical signs of disease appeared.

The level of p-tau181 in CSF increased 11 years before disease onset, and NfL levels, a measure of neurodegeneration, increased 9 years before diagnosis.

These changes were followed by hippocampal atrophy and cognitive decline a few years later.

The results also show “an apparent accelerated change in concentrations of CSF biomarkers followed by a slowing of this change up to the time of diagnosis,” report the authors, led by Jianping Jia, MD, PhD, with the Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China.

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

Time Course of Biomarker Changes

Dr. Jia and colleagues conducted a nested case-control study within the China Cognition and Aging Study (COAST). They matched 648 adults who developed Alzheimer’s disease to 648 who remained cognitively normal. CSF, cognitive, and brain imaging assessments were performed every 2-3 years for a median of about 20 years.

Within both groups, men slightly outnumbered women. At baseline, CSF biomarker levels, cognitive scores, and hippocampal volumes were similar in the two groups. Adults who developed Alzheimer’s disease were more likely than their matched controls to be carriers of the APOE epsilon-4 allele (37% vs 20%).

In terms of CSF Abeta42, the level of this biomarker in those who developed Alzheimer’s disease diverged from the level in controls an estimated 18 years before clinical diagnosis. At that time, the level was lower by a mean 59.13 pg/mL in the Alzheimer’s disease group.

A difference in the ratio of CSF Abeta42 to Abeta40 between the two groups appeared an estimated 14 years before the diagnosis of Alzheimer’s disease (difference in mean values, −0.01 pg/mL).

Differences between the two groups in CSF p-tau181 and total tau concentrations were apparent roughly 11 and 10 years before diagnosis, respectively. At those times, the mean differences in p-tau181 and total tau concentrations were 7.10 pg/mL and 87.10 pg/mL, respectively.

In terms of NfL, a difference between the groups was observed 9 years before diagnosis, with its trajectory progressively deviating from the concentrations observed in cognitively normal groups at that time, to a final mean difference in NfL of 228.29 pg/mL. 

Bilateral hippocampal volume decreased with age in both groups. However, the decrease began to differ between the two groups 8 years before Alzheimer’s disease diagnosis, at which time volume was lower by 358.94 mm³ in the Alzheimer’s disease group compared with the control group.

Average Clinical Dementia Rating–Sum of Boxes (CDR-SB) scores in the Alzheimer’s disease group began to worsen compared with the control group at about 6 years before diagnosis.

As Alzheimer’s disease progressed, changes in CSF biomarkers increased before reaching a plateau. 
 

Important Contribution 

In a linked editorial, Richard Mayeux, MD, Department of Neurology, Columbia University, New York, said the importance of this work “cannot be overstated. Knowledge of the timing of these physiological events is critical to provide clinicians with useful starting points for prevention and therapeutic strategies.”

Dr. Mayeux said this “remarkable” longitudinal study spanning 2 decades “not only confirms the hypotheses of previous investigators but extends and validates the sequence of changes” in sporadic Alzheimer’s disease.

Dr. Mayeux acknowledged that one might consider the finding in this study to be limited owing to the inclusion of only individuals of Han Chinese ancestry. 

However, longitudinal studies of plasma biomarkers in individuals of Asian, European, African, and Hispanic ancestry have shown similar trends in biomarker changes preceding the onset of Alzheimer’s disease, he noted. 

“Ethnic variation in these biomarkers is known, but that fact does not lessen the effect of the results reported. It merely highlights that similar studies must continue and must be inclusive of other groups,” Dr. Mayeux concluded.

The study had no commercial funding. Disclosures for authors and editorialist are available at NEJM.org.

A version of this article appeared on Medscape.com.

A study spanning 20 years helps nail down the timing of biomarker changes that occur in the period between normal cognition and a diagnosis of sporadic Alzheimer’s disease, something that hasn’t previously been extensively investigated in longitudinal studies.

By analyzing cerebral spinal fluid (CSF), as well as cognitive and brain imaging assessments conducted every few years for two decades, researchers were able to plot the course of changing levels of amyloid-beta 42 (Abeta42), phosphorylated tau 181 (p-tau181), and neurofilament light chain (NfL) in adults with Alzheimer’s disease and mark when those levels began to deviate from those of adults without Alzheimer’s disease.

Levels of Abeta42 in CSF and the ratio of Abeta42 to Abeta40 in people who developed Alzheimer’s disease diverged from those of peers who remained cognitively normal at 18 years and 14 years, respectively, before clinical signs of disease appeared.

The level of p-tau181 in CSF increased 11 years before disease onset, and NfL levels, a measure of neurodegeneration, increased 9 years before diagnosis.

These changes were followed by hippocampal atrophy and cognitive decline a few years later.

The results also show “an apparent accelerated change in concentrations of CSF biomarkers followed by a slowing of this change up to the time of diagnosis,” report the authors, led by Jianping Jia, MD, PhD, with the Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China.

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

Time Course of Biomarker Changes

Dr. Jia and colleagues conducted a nested case-control study within the China Cognition and Aging Study (COAST). They matched 648 adults who developed Alzheimer’s disease to 648 who remained cognitively normal. CSF, cognitive, and brain imaging assessments were performed every 2-3 years for a median of about 20 years.

Within both groups, men slightly outnumbered women. At baseline, CSF biomarker levels, cognitive scores, and hippocampal volumes were similar in the two groups. Adults who developed Alzheimer’s disease were more likely than their matched controls to be carriers of the APOE epsilon-4 allele (37% vs 20%).

In terms of CSF Abeta42, the level of this biomarker in those who developed Alzheimer’s disease diverged from the level in controls an estimated 18 years before clinical diagnosis. At that time, the level was lower by a mean 59.13 pg/mL in the Alzheimer’s disease group.

A difference in the ratio of CSF Abeta42 to Abeta40 between the two groups appeared an estimated 14 years before the diagnosis of Alzheimer’s disease (difference in mean values, −0.01 pg/mL).

Differences between the two groups in CSF p-tau181 and total tau concentrations were apparent roughly 11 and 10 years before diagnosis, respectively. At those times, the mean differences in p-tau181 and total tau concentrations were 7.10 pg/mL and 87.10 pg/mL, respectively.

In terms of NfL, a difference between the groups was observed 9 years before diagnosis, with its trajectory progressively deviating from the concentrations observed in cognitively normal groups at that time, to a final mean difference in NfL of 228.29 pg/mL. 

Bilateral hippocampal volume decreased with age in both groups. However, the decrease began to differ between the two groups 8 years before Alzheimer’s disease diagnosis, at which time volume was lower by 358.94 mm³ in the Alzheimer’s disease group compared with the control group.

Average Clinical Dementia Rating–Sum of Boxes (CDR-SB) scores in the Alzheimer’s disease group began to worsen compared with the control group at about 6 years before diagnosis.

As Alzheimer’s disease progressed, changes in CSF biomarkers increased before reaching a plateau. 
 

Important Contribution 

In a linked editorial, Richard Mayeux, MD, Department of Neurology, Columbia University, New York, said the importance of this work “cannot be overstated. Knowledge of the timing of these physiological events is critical to provide clinicians with useful starting points for prevention and therapeutic strategies.”

Dr. Mayeux said this “remarkable” longitudinal study spanning 2 decades “not only confirms the hypotheses of previous investigators but extends and validates the sequence of changes” in sporadic Alzheimer’s disease.

Dr. Mayeux acknowledged that one might consider the finding in this study to be limited owing to the inclusion of only individuals of Han Chinese ancestry. 

However, longitudinal studies of plasma biomarkers in individuals of Asian, European, African, and Hispanic ancestry have shown similar trends in biomarker changes preceding the onset of Alzheimer’s disease, he noted. 

“Ethnic variation in these biomarkers is known, but that fact does not lessen the effect of the results reported. It merely highlights that similar studies must continue and must be inclusive of other groups,” Dr. Mayeux concluded.

The study had no commercial funding. Disclosures for authors and editorialist are available at NEJM.org.

A version of this article appeared on Medscape.com.

A study spanning 20 years helps nail down the timing of biomarker changes that occur in the period between normal cognition and a diagnosis of sporadic Alzheimer’s disease, something that hasn’t previously been extensively investigated in longitudinal studies.

By analyzing cerebral spinal fluid (CSF), as well as cognitive and brain imaging assessments conducted every few years for two decades, researchers were able to plot the course of changing levels of amyloid-beta 42 (Abeta42), phosphorylated tau 181 (p-tau181), and neurofilament light chain (NfL) in adults with Alzheimer’s disease and mark when those levels began to deviate from those of adults without Alzheimer’s disease.

Levels of Abeta42 in CSF and the ratio of Abeta42 to Abeta40 in people who developed Alzheimer’s disease diverged from those of peers who remained cognitively normal at 18 years and 14 years, respectively, before clinical signs of disease appeared.

The level of p-tau181 in CSF increased 11 years before disease onset, and NfL levels, a measure of neurodegeneration, increased 9 years before diagnosis.

These changes were followed by hippocampal atrophy and cognitive decline a few years later.

The results also show “an apparent accelerated change in concentrations of CSF biomarkers followed by a slowing of this change up to the time of diagnosis,” report the authors, led by Jianping Jia, MD, PhD, with the Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China.

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

Time Course of Biomarker Changes

Dr. Jia and colleagues conducted a nested case-control study within the China Cognition and Aging Study (COAST). They matched 648 adults who developed Alzheimer’s disease to 648 who remained cognitively normal. CSF, cognitive, and brain imaging assessments were performed every 2-3 years for a median of about 20 years.

Within both groups, men slightly outnumbered women. At baseline, CSF biomarker levels, cognitive scores, and hippocampal volumes were similar in the two groups. Adults who developed Alzheimer’s disease were more likely than their matched controls to be carriers of the APOE epsilon-4 allele (37% vs 20%).

In terms of CSF Abeta42, the level of this biomarker in those who developed Alzheimer’s disease diverged from the level in controls an estimated 18 years before clinical diagnosis. At that time, the level was lower by a mean 59.13 pg/mL in the Alzheimer’s disease group.

A difference in the ratio of CSF Abeta42 to Abeta40 between the two groups appeared an estimated 14 years before the diagnosis of Alzheimer’s disease (difference in mean values, −0.01 pg/mL).

Differences between the two groups in CSF p-tau181 and total tau concentrations were apparent roughly 11 and 10 years before diagnosis, respectively. At those times, the mean differences in p-tau181 and total tau concentrations were 7.10 pg/mL and 87.10 pg/mL, respectively.

In terms of NfL, a difference between the groups was observed 9 years before diagnosis, with its trajectory progressively deviating from the concentrations observed in cognitively normal groups at that time, to a final mean difference in NfL of 228.29 pg/mL. 

Bilateral hippocampal volume decreased with age in both groups. However, the decrease began to differ between the two groups 8 years before Alzheimer’s disease diagnosis, at which time volume was lower by 358.94 mm³ in the Alzheimer’s disease group compared with the control group.

Average Clinical Dementia Rating–Sum of Boxes (CDR-SB) scores in the Alzheimer’s disease group began to worsen compared with the control group at about 6 years before diagnosis.

As Alzheimer’s disease progressed, changes in CSF biomarkers increased before reaching a plateau. 
 

Important Contribution 

In a linked editorial, Richard Mayeux, MD, Department of Neurology, Columbia University, New York, said the importance of this work “cannot be overstated. Knowledge of the timing of these physiological events is critical to provide clinicians with useful starting points for prevention and therapeutic strategies.”

Dr. Mayeux said this “remarkable” longitudinal study spanning 2 decades “not only confirms the hypotheses of previous investigators but extends and validates the sequence of changes” in sporadic Alzheimer’s disease.

Dr. Mayeux acknowledged that one might consider the finding in this study to be limited owing to the inclusion of only individuals of Han Chinese ancestry. 

However, longitudinal studies of plasma biomarkers in individuals of Asian, European, African, and Hispanic ancestry have shown similar trends in biomarker changes preceding the onset of Alzheimer’s disease, he noted. 

“Ethnic variation in these biomarkers is known, but that fact does not lessen the effect of the results reported. It merely highlights that similar studies must continue and must be inclusive of other groups,” Dr. Mayeux concluded.

The study had no commercial funding. Disclosures for authors and editorialist are available at NEJM.org.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Dear colleagues, I’m Christoph Diener from the medical faculty of University Duisburg-Essen in Germany. Today I would like to tell you about five interesting studies that were published in January 2024.
 

Long COVID

I would like to start with long COVID. There is an ongoing discussion about whether this condition — which means symptoms like dizziness, vertigo, fatigue, headache, and cognitive impairment that persist for more than 6 months — is either a consequence of the infection, functional symptoms, psychosomatic disease, or a depression.

There is an important paper that came out in Science. The group investigated 39 controls and 113 patients who had COVID-19. At 6 months, 40 of them had long COVID. The researchers repeatedly measured more than 6500 proteins in serum. The patients with long COVID had a significant increase in complement activation, which persisted even beyond 6 months. These patients also showed increased tissue lesion markers in the blood and activation of the endothelium.

Also, they had increased platelet activation and autoantibodies with increased anti-cytomegalovirus and anti-Epstein-Barr virus immunoglobulins. These are very strong indicators that COVID-19 leads to long-term changes in our immune system, and different activations of complement factors could explain the variety of symptoms that these patients display. Whether this has consequences for treatment is unclear at the moment.
 

Parkinson’s Classification

Let me come to another issue, which is the future treatment of Parkinson’s disease, covered in a paper in The Lancet Neurology. I think you are all aware that once patients display symptoms like rigidity, bradykinesia, or tremor, it’s most probably too late for neuroprotective therapy because 70% of the dopaminergic neurons are already dead.

The authors propose a new biological diagnosis of the disease in the preclinical state. This early preclinical diagnosis has three components. One is to show the presence of synuclein either in skin biopsy or in serum. The second is proof of neurodegeneration either by MRI or by PET imaging. The third involves genetic markers.

On top of this, we know that we have preclinical manifestations of Parkinson’s disease, like REM sleep disorders, autonomic disturbances, and cognitive impairment. With this new classification, we should be able to identify the preclinical phase of Parkinson’s disease and include these patients in future trials for neuroprotection.
 

Niemann-Pick Disease

My third study, in The New England Journal of Medicine, deals with Niemann-Pick disease type C (Trial of N-Acetyl-l-Leucine in Niemann–Pick Disease Type C. This is a rare autosomal recessive disorder that involves impaired lysosomal storage. This disease, which manifests usually in childhood, goes along with systemic, psychiatric, and neurologic abnormalities, and in particular, ataxia. Until now, there has been only one therapy, with miglustat. which has many side effects.

The group of authors found a new therapeutic approach with N-acetyl-L-leucine, which primarily increases mitochondrial energy production. This was a small, placebo-controlled, crossover trial with 2 x 12 weeks of treatment. This new compound showed efficacy and was very well tolerated. This shows that we definitely need long-term studies with this new, well-tolerated drug in this rare disease.
 

Anticoagulation in Subclinical AF

My fourth study comes from the stroke-prevention field, published in The New England Journal of Medicine. I think you are aware of subclinical atrail fibrillation. These are high-frequency episodes in ECG, usually identified by pacemakers or ECG monitoring systems. The international ARTESIA study included more than 4000 patients randomized either to apixaban 5 mg twice daily or aspirin 81 mg.

After 3.5 years, the investigators showed a small but significant decrease in the rate of stroke, with a relative risk reduction of 37%, but also, unfortunately, a significantly increased risk for major bleeding with apixaban. This means that we need a careful discussion with the patient, the family, and the GP to decide whether these patients should be anticoagulated or not.
 

Migraine and Depression

My final study, published in the European Journal of Neurology, deals with the comorbidity of depression and migraine. This study in the Netherlands included 108 patients treated with erenumab and 90 with fremanezumab; 68 were controls.

They used two depression scales. They showed that treatment with the monoclonal antibodies improved at least one of the two depression scales. I think this is an important study because it indicates that you can improve comorbid depression in people with severe migraine, even if this study did not show a correlation between the reduction in monthly migraine days and the improvement of depression.

What we learned for clinical practice is that we have to identify depression in people with migraine and we have to deal with it. Whether it’s with the treatment of monoclonal antibodies or antidepressant therapy doesn’t really matter.

Dear colleagues, we had interesting studies this month. I think the most spectacular one was published in Science on long COVID. Thank you very much for listening and watching. I’m Christoph Diener from University Duisburg-Essen.
 

Dr. Diener is Professor, Department of Neurology, Stroke Center-Headache Center, University Duisburg-Essen, 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-Pharml Electrocore; Fresenius; GlaxoSmithKline; Grunenthal; Janssen-Cilag; Labrys Biologics Lilly; La Roche; 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; Syngis; St. Jude; Talecris; Thrombogenics; WebMD Global; Weber and Weber; Wyeth; and Yamanouchi.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Dear colleagues, I’m Christoph Diener from the medical faculty of University Duisburg-Essen in Germany. Today I would like to tell you about five interesting studies that were published in January 2024.
 

Long COVID

I would like to start with long COVID. There is an ongoing discussion about whether this condition — which means symptoms like dizziness, vertigo, fatigue, headache, and cognitive impairment that persist for more than 6 months — is either a consequence of the infection, functional symptoms, psychosomatic disease, or a depression.

There is an important paper that came out in Science. The group investigated 39 controls and 113 patients who had COVID-19. At 6 months, 40 of them had long COVID. The researchers repeatedly measured more than 6500 proteins in serum. The patients with long COVID had a significant increase in complement activation, which persisted even beyond 6 months. These patients also showed increased tissue lesion markers in the blood and activation of the endothelium.

Also, they had increased platelet activation and autoantibodies with increased anti-cytomegalovirus and anti-Epstein-Barr virus immunoglobulins. These are very strong indicators that COVID-19 leads to long-term changes in our immune system, and different activations of complement factors could explain the variety of symptoms that these patients display. Whether this has consequences for treatment is unclear at the moment.
 

Parkinson’s Classification

Let me come to another issue, which is the future treatment of Parkinson’s disease, covered in a paper in The Lancet Neurology. I think you are all aware that once patients display symptoms like rigidity, bradykinesia, or tremor, it’s most probably too late for neuroprotective therapy because 70% of the dopaminergic neurons are already dead.

The authors propose a new biological diagnosis of the disease in the preclinical state. This early preclinical diagnosis has three components. One is to show the presence of synuclein either in skin biopsy or in serum. The second is proof of neurodegeneration either by MRI or by PET imaging. The third involves genetic markers.

On top of this, we know that we have preclinical manifestations of Parkinson’s disease, like REM sleep disorders, autonomic disturbances, and cognitive impairment. With this new classification, we should be able to identify the preclinical phase of Parkinson’s disease and include these patients in future trials for neuroprotection.
 

Niemann-Pick Disease

My third study, in The New England Journal of Medicine, deals with Niemann-Pick disease type C (Trial of N-Acetyl-l-Leucine in Niemann–Pick Disease Type C. This is a rare autosomal recessive disorder that involves impaired lysosomal storage. This disease, which manifests usually in childhood, goes along with systemic, psychiatric, and neurologic abnormalities, and in particular, ataxia. Until now, there has been only one therapy, with miglustat. which has many side effects.

The group of authors found a new therapeutic approach with N-acetyl-L-leucine, which primarily increases mitochondrial energy production. This was a small, placebo-controlled, crossover trial with 2 x 12 weeks of treatment. This new compound showed efficacy and was very well tolerated. This shows that we definitely need long-term studies with this new, well-tolerated drug in this rare disease.
 

Anticoagulation in Subclinical AF

My fourth study comes from the stroke-prevention field, published in The New England Journal of Medicine. I think you are aware of subclinical atrail fibrillation. These are high-frequency episodes in ECG, usually identified by pacemakers or ECG monitoring systems. The international ARTESIA study included more than 4000 patients randomized either to apixaban 5 mg twice daily or aspirin 81 mg.

After 3.5 years, the investigators showed a small but significant decrease in the rate of stroke, with a relative risk reduction of 37%, but also, unfortunately, a significantly increased risk for major bleeding with apixaban. This means that we need a careful discussion with the patient, the family, and the GP to decide whether these patients should be anticoagulated or not.
 

Migraine and Depression

My final study, published in the European Journal of Neurology, deals with the comorbidity of depression and migraine. This study in the Netherlands included 108 patients treated with erenumab and 90 with fremanezumab; 68 were controls.

They used two depression scales. They showed that treatment with the monoclonal antibodies improved at least one of the two depression scales. I think this is an important study because it indicates that you can improve comorbid depression in people with severe migraine, even if this study did not show a correlation between the reduction in monthly migraine days and the improvement of depression.

What we learned for clinical practice is that we have to identify depression in people with migraine and we have to deal with it. Whether it’s with the treatment of monoclonal antibodies or antidepressant therapy doesn’t really matter.

Dear colleagues, we had interesting studies this month. I think the most spectacular one was published in Science on long COVID. Thank you very much for listening and watching. I’m Christoph Diener from University Duisburg-Essen.
 

Dr. Diener is Professor, Department of Neurology, Stroke Center-Headache Center, University Duisburg-Essen, 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-Pharml Electrocore; Fresenius; GlaxoSmithKline; Grunenthal; Janssen-Cilag; Labrys Biologics Lilly; La Roche; 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; Syngis; St. Jude; Talecris; Thrombogenics; WebMD Global; Weber and Weber; Wyeth; and Yamanouchi.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Dear colleagues, I’m Christoph Diener from the medical faculty of University Duisburg-Essen in Germany. Today I would like to tell you about five interesting studies that were published in January 2024.
 

Long COVID

I would like to start with long COVID. There is an ongoing discussion about whether this condition — which means symptoms like dizziness, vertigo, fatigue, headache, and cognitive impairment that persist for more than 6 months — is either a consequence of the infection, functional symptoms, psychosomatic disease, or a depression.

There is an important paper that came out in Science. The group investigated 39 controls and 113 patients who had COVID-19. At 6 months, 40 of them had long COVID. The researchers repeatedly measured more than 6500 proteins in serum. The patients with long COVID had a significant increase in complement activation, which persisted even beyond 6 months. These patients also showed increased tissue lesion markers in the blood and activation of the endothelium.

Also, they had increased platelet activation and autoantibodies with increased anti-cytomegalovirus and anti-Epstein-Barr virus immunoglobulins. These are very strong indicators that COVID-19 leads to long-term changes in our immune system, and different activations of complement factors could explain the variety of symptoms that these patients display. Whether this has consequences for treatment is unclear at the moment.
 

Parkinson’s Classification

Let me come to another issue, which is the future treatment of Parkinson’s disease, covered in a paper in The Lancet Neurology. I think you are all aware that once patients display symptoms like rigidity, bradykinesia, or tremor, it’s most probably too late for neuroprotective therapy because 70% of the dopaminergic neurons are already dead.

The authors propose a new biological diagnosis of the disease in the preclinical state. This early preclinical diagnosis has three components. One is to show the presence of synuclein either in skin biopsy or in serum. The second is proof of neurodegeneration either by MRI or by PET imaging. The third involves genetic markers.

On top of this, we know that we have preclinical manifestations of Parkinson’s disease, like REM sleep disorders, autonomic disturbances, and cognitive impairment. With this new classification, we should be able to identify the preclinical phase of Parkinson’s disease and include these patients in future trials for neuroprotection.
 

Niemann-Pick Disease

My third study, in The New England Journal of Medicine, deals with Niemann-Pick disease type C (Trial of N-Acetyl-l-Leucine in Niemann–Pick Disease Type C. This is a rare autosomal recessive disorder that involves impaired lysosomal storage. This disease, which manifests usually in childhood, goes along with systemic, psychiatric, and neurologic abnormalities, and in particular, ataxia. Until now, there has been only one therapy, with miglustat. which has many side effects.

The group of authors found a new therapeutic approach with N-acetyl-L-leucine, which primarily increases mitochondrial energy production. This was a small, placebo-controlled, crossover trial with 2 x 12 weeks of treatment. This new compound showed efficacy and was very well tolerated. This shows that we definitely need long-term studies with this new, well-tolerated drug in this rare disease.
 

Anticoagulation in Subclinical AF

My fourth study comes from the stroke-prevention field, published in The New England Journal of Medicine. I think you are aware of subclinical atrail fibrillation. These are high-frequency episodes in ECG, usually identified by pacemakers or ECG monitoring systems. The international ARTESIA study included more than 4000 patients randomized either to apixaban 5 mg twice daily or aspirin 81 mg.

After 3.5 years, the investigators showed a small but significant decrease in the rate of stroke, with a relative risk reduction of 37%, but also, unfortunately, a significantly increased risk for major bleeding with apixaban. This means that we need a careful discussion with the patient, the family, and the GP to decide whether these patients should be anticoagulated or not.
 

Migraine and Depression

My final study, published in the European Journal of Neurology, deals with the comorbidity of depression and migraine. This study in the Netherlands included 108 patients treated with erenumab and 90 with fremanezumab; 68 were controls.

They used two depression scales. They showed that treatment with the monoclonal antibodies improved at least one of the two depression scales. I think this is an important study because it indicates that you can improve comorbid depression in people with severe migraine, even if this study did not show a correlation between the reduction in monthly migraine days and the improvement of depression.

What we learned for clinical practice is that we have to identify depression in people with migraine and we have to deal with it. Whether it’s with the treatment of monoclonal antibodies or antidepressant therapy doesn’t really matter.

Dear colleagues, we had interesting studies this month. I think the most spectacular one was published in Science on long COVID. Thank you very much for listening and watching. I’m Christoph Diener from University Duisburg-Essen.
 

Dr. Diener is Professor, Department of Neurology, Stroke Center-Headache Center, University Duisburg-Essen, 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-Pharml Electrocore; Fresenius; GlaxoSmithKline; Grunenthal; Janssen-Cilag; Labrys Biologics Lilly; La Roche; 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; Syngis; St. Jude; Talecris; Thrombogenics; WebMD Global; Weber and Weber; Wyeth; and Yamanouchi.

A version of this article appeared on Medscape.com.

Prednisolone may be an effective bridge therapy to ease withdrawal symptoms and improve reversal for patients with migraine whose headaches persist despite them taking an abundance of acute headache medications, a condition known as medication-overuse headache (MOH), an observational study out of South Korea has found.

The study, a post-hoc analysis of the RELEASE multicenter observational cohort study of MOH patients in South Korea, found that patients who took prednisolone as a bridge therapy in the early phase of withdrawal from headache medications, or detoxification, had statistically significant higher rates of MOH reversal at 3 months after enrollment than those who did not, 73.8% versus 57.8% (P = .034)  

Seoul National Univeristy College of Medicine

The reversal trend also was noted at 1 month after treatment, the study authors, led by Mi Ji Lee, MD, PhD, an assistant professor at Seoul National University Hospital, Seoul, South Korea, wrote. “Although an observational study cannot draw a definitive conclusion, our study supports the use of prednisolone for the treatment of MOH in a real-world setting,” Dr. Lee and colleagues wrote.
 

Study methods

The study was a post hoc analysis of the RELEASE study, which stands for Registry for Load and Management of Medication Overuse Headache. RELEASE is a multicenter observational cohort study that has been ongoing in South Korea since April 2020. The post hoc analysis included 309 patients, 59 of whom received prednisolone at a varying dose of 10-40 mg a day, with a varying course of 5-14 days. About 74% of patients (228 of 309) completed the 3-month follow-up period, including 41 in the prednisolone group.

The study used three different forms of medication withdrawal before the patients started prednisolone therapy: abrupt discontinuation; gradual discontinuation concurrent with starting prednisolone; and no withdrawal.

Because of the observational nature of the RELEASE study, participating physicians prescribed prednisolone at their own discretion. The study authors noted prednisolone use was neither randomized nor controlled, which they acknowledged as a limitation.

Dr. Lee and colleagues also acknowledged that newer calcitonin gene–related peptide (CGRP) receptor antagonists may not require detoxification to reverse MOH, but that those therapies are not always available for a variety of reasons, such as reimbursement restrictions, regional distribution issues, and financial issues.

The study also evaluated a number of secondary outcomes. For example, 72% of prednisolone patients achieved MOH reversal 1 month after starting treatment versus 54.9% of the nonprednisolone patients. (P = .33). Prednisolone users also had greater reductions in acute medication days (AMD) at 1 month and scores on headache impact test-6 (HIT-6) at 6 months.

Dr. Lee and colleagues noted that the concept of detoxification, or discontinuing medication overuse, as a treatment for MOH has been controversial due to a lack of high-quality evidence to support the approach. “Nevertheless,” they wrote, “several experts still put withdrawal of medication overuse as an important step of MOH treatment in clinical practice despite limited evidence.”
 

Commentary

Alan Rapoport, MD, a clinical professor of neurology at the David Geffen School of Medicine at University of California, Los Angeles, noted a number of limitations with the study. “It wasn’t a unified population of patients,” he said, “which makes it a little harder to say this medicine worked — worked on whom?” The lack of a treatment regimen — the varied dosing and treatment durations, along with the different withdrawal approaches — are further limitations, Dr. Rapoport said.

Nonetheless, the study is an important addition to the evidence on how to manage medication withdrawal in MOH, said Dr. Rapoport, a past president of the International Headache Society and founder and director emeritus of the New England Center for Headache in Stamford, Connecticut, who has a keen interest in MOH research.

“I think this shows to some extent, although it doesn’t prove it because it’s a whole mixture of patients who were all treated differently by different doctors, but when you put them all together the patients who took steroids did better than the patients who did not,” he said. “The study authors did the best they could with the information they had.”

He termed the study “well-done by well-known authors in South Korea.” As medications such as CGRP receptor antagonists and monoclonal antibodies that target CGRP and its receptors become more available, MOH patients “may not need actual detoxification or steroids in their treatment,” Dr. Rapoport said.

Dr. Lee and co-authors have no disclosures. Dr. Rapoport is editor-in-chief of Neurology Reviews. He disclosed relationships with AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica.

Prednisolone may be an effective bridge therapy to ease withdrawal symptoms and improve reversal for patients with migraine whose headaches persist despite them taking an abundance of acute headache medications, a condition known as medication-overuse headache (MOH), an observational study out of South Korea has found.

The study, a post-hoc analysis of the RELEASE multicenter observational cohort study of MOH patients in South Korea, found that patients who took prednisolone as a bridge therapy in the early phase of withdrawal from headache medications, or detoxification, had statistically significant higher rates of MOH reversal at 3 months after enrollment than those who did not, 73.8% versus 57.8% (P = .034)  

Seoul National Univeristy College of Medicine

The reversal trend also was noted at 1 month after treatment, the study authors, led by Mi Ji Lee, MD, PhD, an assistant professor at Seoul National University Hospital, Seoul, South Korea, wrote. “Although an observational study cannot draw a definitive conclusion, our study supports the use of prednisolone for the treatment of MOH in a real-world setting,” Dr. Lee and colleagues wrote.
 

Study methods

The study was a post hoc analysis of the RELEASE study, which stands for Registry for Load and Management of Medication Overuse Headache. RELEASE is a multicenter observational cohort study that has been ongoing in South Korea since April 2020. The post hoc analysis included 309 patients, 59 of whom received prednisolone at a varying dose of 10-40 mg a day, with a varying course of 5-14 days. About 74% of patients (228 of 309) completed the 3-month follow-up period, including 41 in the prednisolone group.

The study used three different forms of medication withdrawal before the patients started prednisolone therapy: abrupt discontinuation; gradual discontinuation concurrent with starting prednisolone; and no withdrawal.

Because of the observational nature of the RELEASE study, participating physicians prescribed prednisolone at their own discretion. The study authors noted prednisolone use was neither randomized nor controlled, which they acknowledged as a limitation.

Dr. Lee and colleagues also acknowledged that newer calcitonin gene–related peptide (CGRP) receptor antagonists may not require detoxification to reverse MOH, but that those therapies are not always available for a variety of reasons, such as reimbursement restrictions, regional distribution issues, and financial issues.

The study also evaluated a number of secondary outcomes. For example, 72% of prednisolone patients achieved MOH reversal 1 month after starting treatment versus 54.9% of the nonprednisolone patients. (P = .33). Prednisolone users also had greater reductions in acute medication days (AMD) at 1 month and scores on headache impact test-6 (HIT-6) at 6 months.

Dr. Lee and colleagues noted that the concept of detoxification, or discontinuing medication overuse, as a treatment for MOH has been controversial due to a lack of high-quality evidence to support the approach. “Nevertheless,” they wrote, “several experts still put withdrawal of medication overuse as an important step of MOH treatment in clinical practice despite limited evidence.”
 

Commentary

Alan Rapoport, MD, a clinical professor of neurology at the David Geffen School of Medicine at University of California, Los Angeles, noted a number of limitations with the study. “It wasn’t a unified population of patients,” he said, “which makes it a little harder to say this medicine worked — worked on whom?” The lack of a treatment regimen — the varied dosing and treatment durations, along with the different withdrawal approaches — are further limitations, Dr. Rapoport said.

Nonetheless, the study is an important addition to the evidence on how to manage medication withdrawal in MOH, said Dr. Rapoport, a past president of the International Headache Society and founder and director emeritus of the New England Center for Headache in Stamford, Connecticut, who has a keen interest in MOH research.

“I think this shows to some extent, although it doesn’t prove it because it’s a whole mixture of patients who were all treated differently by different doctors, but when you put them all together the patients who took steroids did better than the patients who did not,” he said. “The study authors did the best they could with the information they had.”

He termed the study “well-done by well-known authors in South Korea.” As medications such as CGRP receptor antagonists and monoclonal antibodies that target CGRP and its receptors become more available, MOH patients “may not need actual detoxification or steroids in their treatment,” Dr. Rapoport said.

Dr. Lee and co-authors have no disclosures. Dr. Rapoport is editor-in-chief of Neurology Reviews. He disclosed relationships with AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica.

Prednisolone may be an effective bridge therapy to ease withdrawal symptoms and improve reversal for patients with migraine whose headaches persist despite them taking an abundance of acute headache medications, a condition known as medication-overuse headache (MOH), an observational study out of South Korea has found.

The study, a post-hoc analysis of the RELEASE multicenter observational cohort study of MOH patients in South Korea, found that patients who took prednisolone as a bridge therapy in the early phase of withdrawal from headache medications, or detoxification, had statistically significant higher rates of MOH reversal at 3 months after enrollment than those who did not, 73.8% versus 57.8% (P = .034)  

Seoul National Univeristy College of Medicine

The reversal trend also was noted at 1 month after treatment, the study authors, led by Mi Ji Lee, MD, PhD, an assistant professor at Seoul National University Hospital, Seoul, South Korea, wrote. “Although an observational study cannot draw a definitive conclusion, our study supports the use of prednisolone for the treatment of MOH in a real-world setting,” Dr. Lee and colleagues wrote.
 

Study methods

The study was a post hoc analysis of the RELEASE study, which stands for Registry for Load and Management of Medication Overuse Headache. RELEASE is a multicenter observational cohort study that has been ongoing in South Korea since April 2020. The post hoc analysis included 309 patients, 59 of whom received prednisolone at a varying dose of 10-40 mg a day, with a varying course of 5-14 days. About 74% of patients (228 of 309) completed the 3-month follow-up period, including 41 in the prednisolone group.

The study used three different forms of medication withdrawal before the patients started prednisolone therapy: abrupt discontinuation; gradual discontinuation concurrent with starting prednisolone; and no withdrawal.

Because of the observational nature of the RELEASE study, participating physicians prescribed prednisolone at their own discretion. The study authors noted prednisolone use was neither randomized nor controlled, which they acknowledged as a limitation.

Dr. Lee and colleagues also acknowledged that newer calcitonin gene–related peptide (CGRP) receptor antagonists may not require detoxification to reverse MOH, but that those therapies are not always available for a variety of reasons, such as reimbursement restrictions, regional distribution issues, and financial issues.

The study also evaluated a number of secondary outcomes. For example, 72% of prednisolone patients achieved MOH reversal 1 month after starting treatment versus 54.9% of the nonprednisolone patients. (P = .33). Prednisolone users also had greater reductions in acute medication days (AMD) at 1 month and scores on headache impact test-6 (HIT-6) at 6 months.

Dr. Lee and colleagues noted that the concept of detoxification, or discontinuing medication overuse, as a treatment for MOH has been controversial due to a lack of high-quality evidence to support the approach. “Nevertheless,” they wrote, “several experts still put withdrawal of medication overuse as an important step of MOH treatment in clinical practice despite limited evidence.”
 

Commentary

Alan Rapoport, MD, a clinical professor of neurology at the David Geffen School of Medicine at University of California, Los Angeles, noted a number of limitations with the study. “It wasn’t a unified population of patients,” he said, “which makes it a little harder to say this medicine worked — worked on whom?” The lack of a treatment regimen — the varied dosing and treatment durations, along with the different withdrawal approaches — are further limitations, Dr. Rapoport said.

Nonetheless, the study is an important addition to the evidence on how to manage medication withdrawal in MOH, said Dr. Rapoport, a past president of the International Headache Society and founder and director emeritus of the New England Center for Headache in Stamford, Connecticut, who has a keen interest in MOH research.

“I think this shows to some extent, although it doesn’t prove it because it’s a whole mixture of patients who were all treated differently by different doctors, but when you put them all together the patients who took steroids did better than the patients who did not,” he said. “The study authors did the best they could with the information they had.”

He termed the study “well-done by well-known authors in South Korea.” As medications such as CGRP receptor antagonists and monoclonal antibodies that target CGRP and its receptors become more available, MOH patients “may not need actual detoxification or steroids in their treatment,” Dr. Rapoport said.

Dr. Lee and co-authors have no disclosures. Dr. Rapoport is editor-in-chief of Neurology Reviews. He disclosed relationships with AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica.

The first updated guidelines for specialized epilepsy centers in a decade reflect a shift toward addressing patients’ overall well-being, including recommendations for genetic testing and counseling, mental health screening, and greater attention to special-needs populations. 

The guidelines — the first from the National Association of Epilepsy Centers (NAEC) in a decade — describe the comprehensive services and resources specialized epilepsy centers should provide to improve quality of care for people living with epilepsy.

“In addition to advances in medicine, there has been a shift toward addressing overall well-being beyond seizure management,” Fred A. Lado, MD, PhD, NAEC president and guideline panel cochair, said in a news release. “This includes care for comorbid conditions like anxiety and depression, enhanced communication between the patient and care team, and addressing health disparities in the epilepsy community.

The guidance was developed by a panel of multidisciplinary experts, which is the first time that the NAEC has gone beyond the field of neurology to seek input from other medical specialists and allied health personnel, the panel noted. 

“Expanded guidelines are also sorely needed to help centers and hospitals obtain the resources to provide this level of comprehensive care,” said Dr. Lado, regional director of epilepsy and professor of neurology at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. 

An executive summary of the guidelines was published online in Neurology. 
 

A Multidisciplinary Approach

Epilepsy is one of the most common chronic neurologic conditions worldwide, affecting an estimated 3.4 million people in the United States alone. Recurring seizures can be debilitating and, in some cases, life-threatening. 

To update epilepsy care guidelines, an expert panel of 41 stakeholders with diverse expertise evaluated the latest evidence and reached consensus on 52 recommendations spanning a range of services that make up high-quality epilepsy care. 

“This is exhibited in a greater emphasis on multidisciplinary care conferences, screening for comorbidities of epilepsy, and providing access to other specialty services in addition to the core epilepsy center components of outpatient care, diagnostic procedures, and epilepsy surgery,” they wrote. 

For the first time, the guidelines advise specialized epilepsy centers to offer genetic testing and counseling, provide more education and communication for patients, give greater attention to special-needs populations, employ a care coordinator to organize and facilitate multidisciplinary care, provide mental health screening, and address health disparities and inequities.

“All recommendations quickly reached consensus despite there being such a diverse panel of stakeholders, which emphasizes that the recommendations reflect the important elements of healthcare services that should be in place for an epilepsy center to provide the highest quality of care,” said Susan Arnold, MD, guideline panel co-chair and a pediatric epileptologist at Yale University School of Medicine, New Haven, Connecticut.

“But epilepsy centers will need the resources to provide this comprehensive level of care. We hope the guidelines will help increase health insurer and institutional support and recognition of these recommendations,” Dr. Arnold added. 

The guidelines were funded by NAEC. Dr. Lado has no relevant disclosures. Dr. Arnold holds stock in Pfizer. A complete list of disclosures for the guideline panel is available with the original article. 
 

A version of this article appeared on Medscape.com.

The first updated guidelines for specialized epilepsy centers in a decade reflect a shift toward addressing patients’ overall well-being, including recommendations for genetic testing and counseling, mental health screening, and greater attention to special-needs populations. 

The guidelines — the first from the National Association of Epilepsy Centers (NAEC) in a decade — describe the comprehensive services and resources specialized epilepsy centers should provide to improve quality of care for people living with epilepsy.

“In addition to advances in medicine, there has been a shift toward addressing overall well-being beyond seizure management,” Fred A. Lado, MD, PhD, NAEC president and guideline panel cochair, said in a news release. “This includes care for comorbid conditions like anxiety and depression, enhanced communication between the patient and care team, and addressing health disparities in the epilepsy community.

The guidance was developed by a panel of multidisciplinary experts, which is the first time that the NAEC has gone beyond the field of neurology to seek input from other medical specialists and allied health personnel, the panel noted. 

“Expanded guidelines are also sorely needed to help centers and hospitals obtain the resources to provide this level of comprehensive care,” said Dr. Lado, regional director of epilepsy and professor of neurology at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. 

An executive summary of the guidelines was published online in Neurology. 
 

A Multidisciplinary Approach

Epilepsy is one of the most common chronic neurologic conditions worldwide, affecting an estimated 3.4 million people in the United States alone. Recurring seizures can be debilitating and, in some cases, life-threatening. 

To update epilepsy care guidelines, an expert panel of 41 stakeholders with diverse expertise evaluated the latest evidence and reached consensus on 52 recommendations spanning a range of services that make up high-quality epilepsy care. 

“This is exhibited in a greater emphasis on multidisciplinary care conferences, screening for comorbidities of epilepsy, and providing access to other specialty services in addition to the core epilepsy center components of outpatient care, diagnostic procedures, and epilepsy surgery,” they wrote. 

For the first time, the guidelines advise specialized epilepsy centers to offer genetic testing and counseling, provide more education and communication for patients, give greater attention to special-needs populations, employ a care coordinator to organize and facilitate multidisciplinary care, provide mental health screening, and address health disparities and inequities.

“All recommendations quickly reached consensus despite there being such a diverse panel of stakeholders, which emphasizes that the recommendations reflect the important elements of healthcare services that should be in place for an epilepsy center to provide the highest quality of care,” said Susan Arnold, MD, guideline panel co-chair and a pediatric epileptologist at Yale University School of Medicine, New Haven, Connecticut.

“But epilepsy centers will need the resources to provide this comprehensive level of care. We hope the guidelines will help increase health insurer and institutional support and recognition of these recommendations,” Dr. Arnold added. 

The guidelines were funded by NAEC. Dr. Lado has no relevant disclosures. Dr. Arnold holds stock in Pfizer. A complete list of disclosures for the guideline panel is available with the original article. 
 

A version of this article appeared on Medscape.com.

The first updated guidelines for specialized epilepsy centers in a decade reflect a shift toward addressing patients’ overall well-being, including recommendations for genetic testing and counseling, mental health screening, and greater attention to special-needs populations. 

The guidelines — the first from the National Association of Epilepsy Centers (NAEC) in a decade — describe the comprehensive services and resources specialized epilepsy centers should provide to improve quality of care for people living with epilepsy.

“In addition to advances in medicine, there has been a shift toward addressing overall well-being beyond seizure management,” Fred A. Lado, MD, PhD, NAEC president and guideline panel cochair, said in a news release. “This includes care for comorbid conditions like anxiety and depression, enhanced communication between the patient and care team, and addressing health disparities in the epilepsy community.

The guidance was developed by a panel of multidisciplinary experts, which is the first time that the NAEC has gone beyond the field of neurology to seek input from other medical specialists and allied health personnel, the panel noted. 

“Expanded guidelines are also sorely needed to help centers and hospitals obtain the resources to provide this level of comprehensive care,” said Dr. Lado, regional director of epilepsy and professor of neurology at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. 

An executive summary of the guidelines was published online in Neurology. 
 

A Multidisciplinary Approach

Epilepsy is one of the most common chronic neurologic conditions worldwide, affecting an estimated 3.4 million people in the United States alone. Recurring seizures can be debilitating and, in some cases, life-threatening. 

To update epilepsy care guidelines, an expert panel of 41 stakeholders with diverse expertise evaluated the latest evidence and reached consensus on 52 recommendations spanning a range of services that make up high-quality epilepsy care. 

“This is exhibited in a greater emphasis on multidisciplinary care conferences, screening for comorbidities of epilepsy, and providing access to other specialty services in addition to the core epilepsy center components of outpatient care, diagnostic procedures, and epilepsy surgery,” they wrote. 

For the first time, the guidelines advise specialized epilepsy centers to offer genetic testing and counseling, provide more education and communication for patients, give greater attention to special-needs populations, employ a care coordinator to organize and facilitate multidisciplinary care, provide mental health screening, and address health disparities and inequities.

“All recommendations quickly reached consensus despite there being such a diverse panel of stakeholders, which emphasizes that the recommendations reflect the important elements of healthcare services that should be in place for an epilepsy center to provide the highest quality of care,” said Susan Arnold, MD, guideline panel co-chair and a pediatric epileptologist at Yale University School of Medicine, New Haven, Connecticut.

“But epilepsy centers will need the resources to provide this comprehensive level of care. We hope the guidelines will help increase health insurer and institutional support and recognition of these recommendations,” Dr. Arnold added. 

The guidelines were funded by NAEC. Dr. Lado has no relevant disclosures. Dr. Arnold holds stock in Pfizer. A complete list of disclosures for the guideline panel is available with the original article. 
 

A version of this article appeared on Medscape.com.

Modern technology for recording deep-brain activity involves sharp metal electrodes that penetrate the tissue, causing damage that can compromise the signal and limiting how often they can be used. 

A rapidly growing area in materials science and engineering aims to fix the problem by designing electrodes that are softer, smaller, and flexible — safer for use inside the delicate tissues of the brain. On January 17, researchers from the University of California, San Diego, reported the development of a thin, flexible electrode that can be inserted deep within the brain and communicate with sensors on the surface. 

But what if you could record detailed deep-brain activity without piercing the brain? 

A team of researchers (as it happens, also from UC San Diego) have developed a thin, flexible implant that “resides on the brain’s surface” and “can infer neural activity from deeper layers,” said Duygu Kuzum, PhD, a professor of electrical and computer engineering, who led the research. 

By combining electrical and optical imaging methods, and artificial intelligence, the researchers used the device — a polymer strip packed with graphene electrodes — to predict deep calcium activity from surface signals, according to a proof-of-concept study published this month in Nature Nanotechnology. 

“Almost everything we know about how neurons behave in living brains comes from data collected with either electrophysiology or two-photon imaging,” said neuroscientist Joshua H. Siegle, PhD, of the Allen Institute for Neural Dynamics in Seattle , who not involved in the study. “ Until now, these two methods have rarely been used simultaneously.”

The technology, which has been tested in mice, could help advance our knowledge of how the brain works and may lead to new minimally invasive treatments for neurologic disorders. 
 

Multimodal Neurotech: The Power of 2-in-1

Electrical and optical methods for recording brain activity have been crucial in advancing neurophysiologic science, but each technique has its limits. Electrical recordings provide high “temporal resolution”; they reveal when activation is happening, but not really where. Optical imaging, on the other hand, offers high “spatial resolution,” showing which area of the brain is lighting up, but its measurements may not correspond with the activity’s timing. 

Research over the past decade has explored how to combine and harness the strengths of both methods. One potential solution is to use electrodes made of transparent materials such as graphene, allowing a clear field of view for a microscope during imaging. Recently, University of Pennsylvania scientists used graphene electrodes to illuminate the neural dynamics of seizures. 

But there are challenges. If graphene electrodes are very small — in this case, 20 µm in diameter — they become more resistant to the flow of electricity. Dr. Kuzum and colleagues addressed this by adding tiny platinum particles to improve electrical conductivity. Long graphene wires connect electrodes to the circuit board, but defects in graphene can interrupt the signal, so they made each wire with two layers; any defects in one wire could be hidden by the other.

By combining the two methods (microelectrode arrays and two-photon imaging), the researchers could see both when brain activity was happening and where, including in deeper layers. They discovered a correlation between electrical responses on the surface and cellular calcium activity deeper down. The team used these data to create a neural network (a type of artificial intelligence that learns to recognize patterns) that predicts deep calcium activity from surface-level readings.

The tech could help scientists study brain activity “in a way not possible with current single-function tools,” said Luyao Lu, PhD, professor of biomedical engineering at George Washington University in Washington, DC, who was not involved in the study. It could shed light on interactions between vascular and electrical activity, or explain how place cells (neurons in the hippocampus) are so efficient at creating spatial memory. 

It could also pave the way for minimally invasive neural prosthetics or targeted treatments for neurologic disorders, the researchers say. Implanting the device would be a “straightforward process” similar to placing electrocorticography grids in patients with epilepsy, said Dr. Kuzum. 

But first, the team plans to do more studies in animal models before testing the tech in clinical settings, Dr. Kuzum added.

A version of this article appeared on Medscape.com.

Modern technology for recording deep-brain activity involves sharp metal electrodes that penetrate the tissue, causing damage that can compromise the signal and limiting how often they can be used. 

A rapidly growing area in materials science and engineering aims to fix the problem by designing electrodes that are softer, smaller, and flexible — safer for use inside the delicate tissues of the brain. On January 17, researchers from the University of California, San Diego, reported the development of a thin, flexible electrode that can be inserted deep within the brain and communicate with sensors on the surface. 

But what if you could record detailed deep-brain activity without piercing the brain? 

A team of researchers (as it happens, also from UC San Diego) have developed a thin, flexible implant that “resides on the brain’s surface” and “can infer neural activity from deeper layers,” said Duygu Kuzum, PhD, a professor of electrical and computer engineering, who led the research. 

By combining electrical and optical imaging methods, and artificial intelligence, the researchers used the device — a polymer strip packed with graphene electrodes — to predict deep calcium activity from surface signals, according to a proof-of-concept study published this month in Nature Nanotechnology. 

“Almost everything we know about how neurons behave in living brains comes from data collected with either electrophysiology or two-photon imaging,” said neuroscientist Joshua H. Siegle, PhD, of the Allen Institute for Neural Dynamics in Seattle , who not involved in the study. “ Until now, these two methods have rarely been used simultaneously.”

The technology, which has been tested in mice, could help advance our knowledge of how the brain works and may lead to new minimally invasive treatments for neurologic disorders. 
 

Multimodal Neurotech: The Power of 2-in-1

Electrical and optical methods for recording brain activity have been crucial in advancing neurophysiologic science, but each technique has its limits. Electrical recordings provide high “temporal resolution”; they reveal when activation is happening, but not really where. Optical imaging, on the other hand, offers high “spatial resolution,” showing which area of the brain is lighting up, but its measurements may not correspond with the activity’s timing. 

Research over the past decade has explored how to combine and harness the strengths of both methods. One potential solution is to use electrodes made of transparent materials such as graphene, allowing a clear field of view for a microscope during imaging. Recently, University of Pennsylvania scientists used graphene electrodes to illuminate the neural dynamics of seizures. 

But there are challenges. If graphene electrodes are very small — in this case, 20 µm in diameter — they become more resistant to the flow of electricity. Dr. Kuzum and colleagues addressed this by adding tiny platinum particles to improve electrical conductivity. Long graphene wires connect electrodes to the circuit board, but defects in graphene can interrupt the signal, so they made each wire with two layers; any defects in one wire could be hidden by the other.

By combining the two methods (microelectrode arrays and two-photon imaging), the researchers could see both when brain activity was happening and where, including in deeper layers. They discovered a correlation between electrical responses on the surface and cellular calcium activity deeper down. The team used these data to create a neural network (a type of artificial intelligence that learns to recognize patterns) that predicts deep calcium activity from surface-level readings.

The tech could help scientists study brain activity “in a way not possible with current single-function tools,” said Luyao Lu, PhD, professor of biomedical engineering at George Washington University in Washington, DC, who was not involved in the study. It could shed light on interactions between vascular and electrical activity, or explain how place cells (neurons in the hippocampus) are so efficient at creating spatial memory. 

It could also pave the way for minimally invasive neural prosthetics or targeted treatments for neurologic disorders, the researchers say. Implanting the device would be a “straightforward process” similar to placing electrocorticography grids in patients with epilepsy, said Dr. Kuzum. 

But first, the team plans to do more studies in animal models before testing the tech in clinical settings, Dr. Kuzum added.

A version of this article appeared on Medscape.com.

Modern technology for recording deep-brain activity involves sharp metal electrodes that penetrate the tissue, causing damage that can compromise the signal and limiting how often they can be used. 

A rapidly growing area in materials science and engineering aims to fix the problem by designing electrodes that are softer, smaller, and flexible — safer for use inside the delicate tissues of the brain. On January 17, researchers from the University of California, San Diego, reported the development of a thin, flexible electrode that can be inserted deep within the brain and communicate with sensors on the surface. 

But what if you could record detailed deep-brain activity without piercing the brain? 

A team of researchers (as it happens, also from UC San Diego) have developed a thin, flexible implant that “resides on the brain’s surface” and “can infer neural activity from deeper layers,” said Duygu Kuzum, PhD, a professor of electrical and computer engineering, who led the research. 

By combining electrical and optical imaging methods, and artificial intelligence, the researchers used the device — a polymer strip packed with graphene electrodes — to predict deep calcium activity from surface signals, according to a proof-of-concept study published this month in Nature Nanotechnology. 

“Almost everything we know about how neurons behave in living brains comes from data collected with either electrophysiology or two-photon imaging,” said neuroscientist Joshua H. Siegle, PhD, of the Allen Institute for Neural Dynamics in Seattle , who not involved in the study. “ Until now, these two methods have rarely been used simultaneously.”

The technology, which has been tested in mice, could help advance our knowledge of how the brain works and may lead to new minimally invasive treatments for neurologic disorders. 
 

Multimodal Neurotech: The Power of 2-in-1

Electrical and optical methods for recording brain activity have been crucial in advancing neurophysiologic science, but each technique has its limits. Electrical recordings provide high “temporal resolution”; they reveal when activation is happening, but not really where. Optical imaging, on the other hand, offers high “spatial resolution,” showing which area of the brain is lighting up, but its measurements may not correspond with the activity’s timing. 

Research over the past decade has explored how to combine and harness the strengths of both methods. One potential solution is to use electrodes made of transparent materials such as graphene, allowing a clear field of view for a microscope during imaging. Recently, University of Pennsylvania scientists used graphene electrodes to illuminate the neural dynamics of seizures. 

But there are challenges. If graphene electrodes are very small — in this case, 20 µm in diameter — they become more resistant to the flow of electricity. Dr. Kuzum and colleagues addressed this by adding tiny platinum particles to improve electrical conductivity. Long graphene wires connect electrodes to the circuit board, but defects in graphene can interrupt the signal, so they made each wire with two layers; any defects in one wire could be hidden by the other.

By combining the two methods (microelectrode arrays and two-photon imaging), the researchers could see both when brain activity was happening and where, including in deeper layers. They discovered a correlation between electrical responses on the surface and cellular calcium activity deeper down. The team used these data to create a neural network (a type of artificial intelligence that learns to recognize patterns) that predicts deep calcium activity from surface-level readings.

The tech could help scientists study brain activity “in a way not possible with current single-function tools,” said Luyao Lu, PhD, professor of biomedical engineering at George Washington University in Washington, DC, who was not involved in the study. It could shed light on interactions between vascular and electrical activity, or explain how place cells (neurons in the hippocampus) are so efficient at creating spatial memory. 

It could also pave the way for minimally invasive neural prosthetics or targeted treatments for neurologic disorders, the researchers say. Implanting the device would be a “straightforward process” similar to placing electrocorticography grids in patients with epilepsy, said Dr. Kuzum. 

But first, the team plans to do more studies in animal models before testing the tech in clinical settings, Dr. Kuzum added.

A version of this article appeared on Medscape.com.

TOPLINE:

A daily low dose of colchicine significantly reduces ischemic cardiovascular events in patients with type 2 diabetes (T2D) and a recent myocardial infarction (MI). 

METHODOLOGY:

• After an MI, patients with vs without T2D have a higher risk for another cardiovascular event.
• The Colchicine Cardiovascular Outcomes Trial (COLCOT), a randomized, double-blinded trial, found a lower risk for ischemic cardiovascular events with 0.5 mg colchicine taken daily vs placebo, initiated within 30 days of an MI.
• Researchers conducted a prespecified subgroup analysis of 959 adult patients with T2D (mean age, 62.4 years; 22.2% women) in COLCOT (462 patients in colchicine and 497 patients in placebo groups).
• The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization within a median 23 months.
• The patients were taking a variety of appropriate medications, including aspirin and another antiplatelet agent and a statin (98%-99%) and metformin (75%-76%).

TAKEAWAY:

• The risk for the primary endpoint was reduced by 35% in patients with T2D who received colchicine than in those who received placebo (hazard ratio, 0.65; P = .03).
• The primary endpoint event rate per 100 patient-months was significantly lower in the colchicine group than in the placebo group (rate ratio, 0.53; P = .01).
• The frequencies of adverse events were similar in both the treatment and placebo groups (14.6% and 12.8%, respectively; P = .41), with gastrointestinal adverse events being the most common.
• In COLCOT, patients with T2D had a 1.86-fold higher risk for a primary endpoint cardiovascular event, but there was no significant difference in the primary endpoint between those with and without T2D on colchicine.

IN PRACTICE:

“Patients with both T2D and a recent MI derive a large benefit from inflammation-reducing therapy with colchicine,” the authors noted.

SOURCE:

This study, led by François Roubille, University Hospital of Montpellier, France, was published online on January 5, 2024, in Diabetes Care. 

LIMITATIONS:

Patients were not stratified at inclusion for the presence of diabetes. Also, the study did not evaluate the role of glycated hemoglobin and low-density lipoprotein cholesterol, as well as the effects of different glucose-lowering medications or possible hypoglycemic episodes.

DISCLOSURES:

The COLCOT study was funded by the Government of Quebec, the Canadian Institutes of Health Research, and philanthropic foundations. Coauthors Jean-Claude Tardif and Wolfgang Koenig declared receiving research grants, honoraria, advisory board fees, and lecture fees from pharmaceutical companies, as well as having other ties with various sources.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A daily low dose of colchicine significantly reduces ischemic cardiovascular events in patients with type 2 diabetes (T2D) and a recent myocardial infarction (MI). 

METHODOLOGY:

• After an MI, patients with vs without T2D have a higher risk for another cardiovascular event.
• The Colchicine Cardiovascular Outcomes Trial (COLCOT), a randomized, double-blinded trial, found a lower risk for ischemic cardiovascular events with 0.5 mg colchicine taken daily vs placebo, initiated within 30 days of an MI.
• Researchers conducted a prespecified subgroup analysis of 959 adult patients with T2D (mean age, 62.4 years; 22.2% women) in COLCOT (462 patients in colchicine and 497 patients in placebo groups).
• The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization within a median 23 months.
• The patients were taking a variety of appropriate medications, including aspirin and another antiplatelet agent and a statin (98%-99%) and metformin (75%-76%).

TAKEAWAY:

• The risk for the primary endpoint was reduced by 35% in patients with T2D who received colchicine than in those who received placebo (hazard ratio, 0.65; P = .03).
• The primary endpoint event rate per 100 patient-months was significantly lower in the colchicine group than in the placebo group (rate ratio, 0.53; P = .01).
• The frequencies of adverse events were similar in both the treatment and placebo groups (14.6% and 12.8%, respectively; P = .41), with gastrointestinal adverse events being the most common.
• In COLCOT, patients with T2D had a 1.86-fold higher risk for a primary endpoint cardiovascular event, but there was no significant difference in the primary endpoint between those with and without T2D on colchicine.

IN PRACTICE:

“Patients with both T2D and a recent MI derive a large benefit from inflammation-reducing therapy with colchicine,” the authors noted.

SOURCE:

This study, led by François Roubille, University Hospital of Montpellier, France, was published online on January 5, 2024, in Diabetes Care. 

LIMITATIONS:

Patients were not stratified at inclusion for the presence of diabetes. Also, the study did not evaluate the role of glycated hemoglobin and low-density lipoprotein cholesterol, as well as the effects of different glucose-lowering medications or possible hypoglycemic episodes.

DISCLOSURES:

The COLCOT study was funded by the Government of Quebec, the Canadian Institutes of Health Research, and philanthropic foundations. Coauthors Jean-Claude Tardif and Wolfgang Koenig declared receiving research grants, honoraria, advisory board fees, and lecture fees from pharmaceutical companies, as well as having other ties with various sources.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A daily low dose of colchicine significantly reduces ischemic cardiovascular events in patients with type 2 diabetes (T2D) and a recent myocardial infarction (MI). 

METHODOLOGY:

• After an MI, patients with vs without T2D have a higher risk for another cardiovascular event.
• The Colchicine Cardiovascular Outcomes Trial (COLCOT), a randomized, double-blinded trial, found a lower risk for ischemic cardiovascular events with 0.5 mg colchicine taken daily vs placebo, initiated within 30 days of an MI.
• Researchers conducted a prespecified subgroup analysis of 959 adult patients with T2D (mean age, 62.4 years; 22.2% women) in COLCOT (462 patients in colchicine and 497 patients in placebo groups).
• The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization within a median 23 months.
• The patients were taking a variety of appropriate medications, including aspirin and another antiplatelet agent and a statin (98%-99%) and metformin (75%-76%).

TAKEAWAY:

• The risk for the primary endpoint was reduced by 35% in patients with T2D who received colchicine than in those who received placebo (hazard ratio, 0.65; P = .03).
• The primary endpoint event rate per 100 patient-months was significantly lower in the colchicine group than in the placebo group (rate ratio, 0.53; P = .01).
• The frequencies of adverse events were similar in both the treatment and placebo groups (14.6% and 12.8%, respectively; P = .41), with gastrointestinal adverse events being the most common.
• In COLCOT, patients with T2D had a 1.86-fold higher risk for a primary endpoint cardiovascular event, but there was no significant difference in the primary endpoint between those with and without T2D on colchicine.

IN PRACTICE:

“Patients with both T2D and a recent MI derive a large benefit from inflammation-reducing therapy with colchicine,” the authors noted.

SOURCE:

This study, led by François Roubille, University Hospital of Montpellier, France, was published online on January 5, 2024, in Diabetes Care. 

LIMITATIONS:

Patients were not stratified at inclusion for the presence of diabetes. Also, the study did not evaluate the role of glycated hemoglobin and low-density lipoprotein cholesterol, as well as the effects of different glucose-lowering medications or possible hypoglycemic episodes.

DISCLOSURES:

The COLCOT study was funded by the Government of Quebec, the Canadian Institutes of Health Research, and philanthropic foundations. Coauthors Jean-Claude Tardif and Wolfgang Koenig declared receiving research grants, honoraria, advisory board fees, and lecture fees from pharmaceutical companies, as well as having other ties with various sources.
 

A version of this article appeared on Medscape.com.

When pediatric patients with epilepsy shift to adult care, inherent challenges are complicated by a near-total lack of efforts to smooth the transition, according to a recent survey. Many respondents received little to no information regarding the process, and many adults were still receiving care from family physicians or pediatric neurologists. The study was published online in Epilepsy & Behavior.

Room for Improvement

“We are not doing as good a job with planning for transition as we should,” said Elaine C. Wirrell, MD, who was not involved with the study. “It is not just a simple issue of sending your patient to an adult neurologist. Transition is a process that happens over time, so we need to do a better job getting our families ready for moving on to an adult provider.” Dr. Wirrell is director of pediatric epilepsy and professor of neurology at the Mayo Clinic in Rochester, Minnesota.

Mayo Clinic

Clumsy Transitions

Investigators distributed a 25-question survey to patients and caregivers who attended the 2019 Epilepsy Awareness Day at Disneyland, and through online support groups in North America. Among 58 responses, 32 came from patients between ages 12 and 17 years or their caregivers.

Despite attempts to recruit a diverse cross-section of respondents, most patients had severe epilepsy and comorbidities: 43% had daily or weekly seizures; 45% were on three or more antiseizure medications; and 74% had intellectual disabilities.

Many children with early-life epilepsies suffer from developmental and epileptic encephalopathy, which has associated non-seizure symptoms including learning challenges, behavioral issues, and other medical concerns, Dr. Wirrell said. Therefore, she said, finding a neurologist who treats adults — and has the expertise and interest to care for such patients — can be difficult.

“We’re seeing many patients not making that transition, or maybe not making it appropriately, so they’re not necessarily getting to the providers who have the most expertise in managing their epilepsy.” Among adults surveyed, 27% were still being followed by pediatric neurologists, and 35% were visiting family doctors for epilepsy-related treatment.

Because the needs of children with complex epilepsy can extend well beyond neurology, Dr. Wirrell added, managing such cases often requires multidisciplinary pediatric teams. “Finding that team on the adult side is more challenging.” As a result, she said, patients may transfer their neurology care without getting additional support for comorbidities such as mood disorders and learning disabilities.

The foregoing challenges are complicated by the fact that pediatric neurologists often lack the time (and in the United States, reimbursement) to adequately address the transition process, said Dr. Wirrell. Providers in freestanding children’s hospitals may face additional challenges coordinating with adult-care providers outside their facilities, she said.

“There’s also potentially a reluctance of both families and physicians to transition the patient on, because there’s concern that maybe there isn’t anybody on the adult side who is able to do as good a job as what they have on the pediatric side.”
 

Well-Coordinated Transitions Should Have No Surprises

Transition should be a planned, independence-promoting process that results in smooth, well-coordinated movement of pediatric patients into adult care — one without surprises or disconnections, the authors wrote. However, 55% of respondents never heard the term “transition” from any provider, even though 69% of patients were being treated in academic specialty centers.

Among 12- to 17-year-olds, 72% had never discussed transition with their healthcare team. That figure includes no 17-year-olds. Approximately 90% of respondents said they received sufficient time during healthcare visits, but 54% reported feeling stressed when moving from pediatric to adult care.

Given resource constraints in many pediatric epilepsy programs, the study authors recommended patient-empowerment tools such as a transition toolkit to help patients and families navigate the transition process even in places without formal transition programs.

“Many of these children are coming over with boatloads of medical records,” Dr. Wirrell said. “It’s not fair to the adult provider, who then has to go through all those records.” Instead, she said, pediatric teams should provide succinct summaries of relevant test results, medication side effects, prior treatments tried, and the like. “Those summaries are critically important so that we can get information to the person who needs it.”

Although successful transition requires significant coordination, she added, much of the process can often be handled by nonphysicians. “There are some very good nurse-led transition programs. Often, we can have a nurse providing education to the family and even potentially having a joint visit with an adult epilepsy nurse for complex patients.”

Pediatric providers also must know when to begin the transition process, Dr. Wirrell said. As soon as patients are 13 or 14 years old, she suggested discussing the process with them and their families every 6 to 12 months, covering specifics ranging from how to order medications to why adult patients may need power of attorney designees.

On a broader scale, said Dr. Wirrell, a smooth handoff requires planning. Fortunately, she said, the topic is becoming a significant priority for a growing number of children’s hospitals specific not only to epilepsy, but also to other chronic illnesses.

Dr. Wirrell is co–editor-in-chief for epilepsy.com. She reports no relevant financial interests.

When pediatric patients with epilepsy shift to adult care, inherent challenges are complicated by a near-total lack of efforts to smooth the transition, according to a recent survey. Many respondents received little to no information regarding the process, and many adults were still receiving care from family physicians or pediatric neurologists. The study was published online in Epilepsy & Behavior.

Room for Improvement

“We are not doing as good a job with planning for transition as we should,” said Elaine C. Wirrell, MD, who was not involved with the study. “It is not just a simple issue of sending your patient to an adult neurologist. Transition is a process that happens over time, so we need to do a better job getting our families ready for moving on to an adult provider.” Dr. Wirrell is director of pediatric epilepsy and professor of neurology at the Mayo Clinic in Rochester, Minnesota.

Mayo Clinic

Clumsy Transitions

Investigators distributed a 25-question survey to patients and caregivers who attended the 2019 Epilepsy Awareness Day at Disneyland, and through online support groups in North America. Among 58 responses, 32 came from patients between ages 12 and 17 years or their caregivers.

Despite attempts to recruit a diverse cross-section of respondents, most patients had severe epilepsy and comorbidities: 43% had daily or weekly seizures; 45% were on three or more antiseizure medications; and 74% had intellectual disabilities.

Many children with early-life epilepsies suffer from developmental and epileptic encephalopathy, which has associated non-seizure symptoms including learning challenges, behavioral issues, and other medical concerns, Dr. Wirrell said. Therefore, she said, finding a neurologist who treats adults — and has the expertise and interest to care for such patients — can be difficult.

“We’re seeing many patients not making that transition, or maybe not making it appropriately, so they’re not necessarily getting to the providers who have the most expertise in managing their epilepsy.” Among adults surveyed, 27% were still being followed by pediatric neurologists, and 35% were visiting family doctors for epilepsy-related treatment.

Because the needs of children with complex epilepsy can extend well beyond neurology, Dr. Wirrell added, managing such cases often requires multidisciplinary pediatric teams. “Finding that team on the adult side is more challenging.” As a result, she said, patients may transfer their neurology care without getting additional support for comorbidities such as mood disorders and learning disabilities.

The foregoing challenges are complicated by the fact that pediatric neurologists often lack the time (and in the United States, reimbursement) to adequately address the transition process, said Dr. Wirrell. Providers in freestanding children’s hospitals may face additional challenges coordinating with adult-care providers outside their facilities, she said.

“There’s also potentially a reluctance of both families and physicians to transition the patient on, because there’s concern that maybe there isn’t anybody on the adult side who is able to do as good a job as what they have on the pediatric side.”
 

Well-Coordinated Transitions Should Have No Surprises

Transition should be a planned, independence-promoting process that results in smooth, well-coordinated movement of pediatric patients into adult care — one without surprises or disconnections, the authors wrote. However, 55% of respondents never heard the term “transition” from any provider, even though 69% of patients were being treated in academic specialty centers.

Among 12- to 17-year-olds, 72% had never discussed transition with their healthcare team. That figure includes no 17-year-olds. Approximately 90% of respondents said they received sufficient time during healthcare visits, but 54% reported feeling stressed when moving from pediatric to adult care.

Given resource constraints in many pediatric epilepsy programs, the study authors recommended patient-empowerment tools such as a transition toolkit to help patients and families navigate the transition process even in places without formal transition programs.

“Many of these children are coming over with boatloads of medical records,” Dr. Wirrell said. “It’s not fair to the adult provider, who then has to go through all those records.” Instead, she said, pediatric teams should provide succinct summaries of relevant test results, medication side effects, prior treatments tried, and the like. “Those summaries are critically important so that we can get information to the person who needs it.”

Although successful transition requires significant coordination, she added, much of the process can often be handled by nonphysicians. “There are some very good nurse-led transition programs. Often, we can have a nurse providing education to the family and even potentially having a joint visit with an adult epilepsy nurse for complex patients.”

Pediatric providers also must know when to begin the transition process, Dr. Wirrell said. As soon as patients are 13 or 14 years old, she suggested discussing the process with them and their families every 6 to 12 months, covering specifics ranging from how to order medications to why adult patients may need power of attorney designees.

On a broader scale, said Dr. Wirrell, a smooth handoff requires planning. Fortunately, she said, the topic is becoming a significant priority for a growing number of children’s hospitals specific not only to epilepsy, but also to other chronic illnesses.

Dr. Wirrell is co–editor-in-chief for epilepsy.com. She reports no relevant financial interests.

When pediatric patients with epilepsy shift to adult care, inherent challenges are complicated by a near-total lack of efforts to smooth the transition, according to a recent survey. Many respondents received little to no information regarding the process, and many adults were still receiving care from family physicians or pediatric neurologists. The study was published online in Epilepsy & Behavior.

Room for Improvement

“We are not doing as good a job with planning for transition as we should,” said Elaine C. Wirrell, MD, who was not involved with the study. “It is not just a simple issue of sending your patient to an adult neurologist. Transition is a process that happens over time, so we need to do a better job getting our families ready for moving on to an adult provider.” Dr. Wirrell is director of pediatric epilepsy and professor of neurology at the Mayo Clinic in Rochester, Minnesota.

Mayo Clinic

Clumsy Transitions

Investigators distributed a 25-question survey to patients and caregivers who attended the 2019 Epilepsy Awareness Day at Disneyland, and through online support groups in North America. Among 58 responses, 32 came from patients between ages 12 and 17 years or their caregivers.

Despite attempts to recruit a diverse cross-section of respondents, most patients had severe epilepsy and comorbidities: 43% had daily or weekly seizures; 45% were on three or more antiseizure medications; and 74% had intellectual disabilities.

Many children with early-life epilepsies suffer from developmental and epileptic encephalopathy, which has associated non-seizure symptoms including learning challenges, behavioral issues, and other medical concerns, Dr. Wirrell said. Therefore, she said, finding a neurologist who treats adults — and has the expertise and interest to care for such patients — can be difficult.

“We’re seeing many patients not making that transition, or maybe not making it appropriately, so they’re not necessarily getting to the providers who have the most expertise in managing their epilepsy.” Among adults surveyed, 27% were still being followed by pediatric neurologists, and 35% were visiting family doctors for epilepsy-related treatment.

Because the needs of children with complex epilepsy can extend well beyond neurology, Dr. Wirrell added, managing such cases often requires multidisciplinary pediatric teams. “Finding that team on the adult side is more challenging.” As a result, she said, patients may transfer their neurology care without getting additional support for comorbidities such as mood disorders and learning disabilities.

The foregoing challenges are complicated by the fact that pediatric neurologists often lack the time (and in the United States, reimbursement) to adequately address the transition process, said Dr. Wirrell. Providers in freestanding children’s hospitals may face additional challenges coordinating with adult-care providers outside their facilities, she said.

“There’s also potentially a reluctance of both families and physicians to transition the patient on, because there’s concern that maybe there isn’t anybody on the adult side who is able to do as good a job as what they have on the pediatric side.”
 

Well-Coordinated Transitions Should Have No Surprises

Transition should be a planned, independence-promoting process that results in smooth, well-coordinated movement of pediatric patients into adult care — one without surprises or disconnections, the authors wrote. However, 55% of respondents never heard the term “transition” from any provider, even though 69% of patients were being treated in academic specialty centers.

Among 12- to 17-year-olds, 72% had never discussed transition with their healthcare team. That figure includes no 17-year-olds. Approximately 90% of respondents said they received sufficient time during healthcare visits, but 54% reported feeling stressed when moving from pediatric to adult care.

Given resource constraints in many pediatric epilepsy programs, the study authors recommended patient-empowerment tools such as a transition toolkit to help patients and families navigate the transition process even in places without formal transition programs.

“Many of these children are coming over with boatloads of medical records,” Dr. Wirrell said. “It’s not fair to the adult provider, who then has to go through all those records.” Instead, she said, pediatric teams should provide succinct summaries of relevant test results, medication side effects, prior treatments tried, and the like. “Those summaries are critically important so that we can get information to the person who needs it.”

Although successful transition requires significant coordination, she added, much of the process can often be handled by nonphysicians. “There are some very good nurse-led transition programs. Often, we can have a nurse providing education to the family and even potentially having a joint visit with an adult epilepsy nurse for complex patients.”

Pediatric providers also must know when to begin the transition process, Dr. Wirrell said. As soon as patients are 13 or 14 years old, she suggested discussing the process with them and their families every 6 to 12 months, covering specifics ranging from how to order medications to why adult patients may need power of attorney designees.

On a broader scale, said Dr. Wirrell, a smooth handoff requires planning. Fortunately, she said, the topic is becoming a significant priority for a growing number of children’s hospitals specific not only to epilepsy, but also to other chronic illnesses.

Dr. Wirrell is co–editor-in-chief for epilepsy.com. She reports no relevant financial interests.