Erik Greb

PHILADELPHIA – The association between vitamin D insufficiency and multiple sclerosis (MS) outcome in children with acquired demyelinating syndromes (ADS) partly relates to skin pigmentation, according to research described at the annual meeting of the American Academy of Neurology. Future research will be required to understand the interactions between dietary vitamin D ingestion, sun exposure, pigmentation of sun-exposed skin, seasonal vitamin D concentrations, and the genetic influences of vitamin D pathways with MS risk.

Race, vitamin D status, HLA-DRB1*15 genotype, and place of residence during childhood all affect the risk of MS. The place of residence also can affect exposure to ultraviolet radiation and, thus, dermal pigmentation.

Candice Dunn, a clinical research coordinator at the Children’s Hospital of Philadelphia, and colleagues conducted a prospective study to determine whether HLA-DRB1*15 status, 25-hydroxyvitamin D (25[OH]D) levels measured at baseline, and skin tone are associated with MS outcome in children with ADS. They enrolled 259 children with incident ADS in a multisite study in Toronto and Philadelphia (latitudes 43° to 51°). The investigators measured non–sun-exposed upper inner arm melanin content using the DSM II ColorMeter device. They measured 25(OH)D concentrations in serum obtained within 60 days of symptom onset and compared them with laboratory-reported normative values. Vitamin D insufficiency was defined as 25(OH)D less than 75 nmol/L. Ms. Dunn and colleagues quantified HLA-DRB1*15 alleles using allele-specific polymerase chain reaction amplification. Statistical analysis was performed using Spearman correlation models and Wilcoxon or Kruskal-Wallis tests as appropriate.

In all, 68 children were diagnosed with MS, 191 remained monophasic (monoADS). Approximately 46% of children with MS were HLA-DRB1*15-positive, compared with 29.9% of monoADS children. In addition, children with MS had significantly lower 25(OH)D levels (mean, 45.4 nmol/L) than monoADS children (mean, 61.9 nmol/L) at baseline. Non–sun-exposed skin tone measured in the upper inner arm did not differ between children diagnosed with MS (mean melanin index, 46.4) and monoADS (mean melanin index, 43.5). Furthermore, 25(OH)D levels correlated with upper inner arm melanin index in the MS group, but not in children with monoADS.

Ms. Dunn had nothing to disclose, but various coauthors have received compensation from companies such as Novartis, Merck, Teva, Celgene, and Genentech.
 

[email protected]

SOURCE: Dunn C et al. AAN 2019, Abstract S19.007.

PHILADELPHIA – The association between vitamin D insufficiency and multiple sclerosis (MS) outcome in children with acquired demyelinating syndromes (ADS) partly relates to skin pigmentation, according to research described at the annual meeting of the American Academy of Neurology. Future research will be required to understand the interactions between dietary vitamin D ingestion, sun exposure, pigmentation of sun-exposed skin, seasonal vitamin D concentrations, and the genetic influences of vitamin D pathways with MS risk.

Race, vitamin D status, HLA-DRB1*15 genotype, and place of residence during childhood all affect the risk of MS. The place of residence also can affect exposure to ultraviolet radiation and, thus, dermal pigmentation.

Candice Dunn, a clinical research coordinator at the Children’s Hospital of Philadelphia, and colleagues conducted a prospective study to determine whether HLA-DRB1*15 status, 25-hydroxyvitamin D (25[OH]D) levels measured at baseline, and skin tone are associated with MS outcome in children with ADS. They enrolled 259 children with incident ADS in a multisite study in Toronto and Philadelphia (latitudes 43° to 51°). The investigators measured non–sun-exposed upper inner arm melanin content using the DSM II ColorMeter device. They measured 25(OH)D concentrations in serum obtained within 60 days of symptom onset and compared them with laboratory-reported normative values. Vitamin D insufficiency was defined as 25(OH)D less than 75 nmol/L. Ms. Dunn and colleagues quantified HLA-DRB1*15 alleles using allele-specific polymerase chain reaction amplification. Statistical analysis was performed using Spearman correlation models and Wilcoxon or Kruskal-Wallis tests as appropriate.

In all, 68 children were diagnosed with MS, 191 remained monophasic (monoADS). Approximately 46% of children with MS were HLA-DRB1*15-positive, compared with 29.9% of monoADS children. In addition, children with MS had significantly lower 25(OH)D levels (mean, 45.4 nmol/L) than monoADS children (mean, 61.9 nmol/L) at baseline. Non–sun-exposed skin tone measured in the upper inner arm did not differ between children diagnosed with MS (mean melanin index, 46.4) and monoADS (mean melanin index, 43.5). Furthermore, 25(OH)D levels correlated with upper inner arm melanin index in the MS group, but not in children with monoADS.

Ms. Dunn had nothing to disclose, but various coauthors have received compensation from companies such as Novartis, Merck, Teva, Celgene, and Genentech.
 

[email protected]

SOURCE: Dunn C et al. AAN 2019, Abstract S19.007.

PHILADELPHIA – The association between vitamin D insufficiency and multiple sclerosis (MS) outcome in children with acquired demyelinating syndromes (ADS) partly relates to skin pigmentation, according to research described at the annual meeting of the American Academy of Neurology. Future research will be required to understand the interactions between dietary vitamin D ingestion, sun exposure, pigmentation of sun-exposed skin, seasonal vitamin D concentrations, and the genetic influences of vitamin D pathways with MS risk.

Race, vitamin D status, HLA-DRB1*15 genotype, and place of residence during childhood all affect the risk of MS. The place of residence also can affect exposure to ultraviolet radiation and, thus, dermal pigmentation.

Candice Dunn, a clinical research coordinator at the Children’s Hospital of Philadelphia, and colleagues conducted a prospective study to determine whether HLA-DRB1*15 status, 25-hydroxyvitamin D (25[OH]D) levels measured at baseline, and skin tone are associated with MS outcome in children with ADS. They enrolled 259 children with incident ADS in a multisite study in Toronto and Philadelphia (latitudes 43° to 51°). The investigators measured non–sun-exposed upper inner arm melanin content using the DSM II ColorMeter device. They measured 25(OH)D concentrations in serum obtained within 60 days of symptom onset and compared them with laboratory-reported normative values. Vitamin D insufficiency was defined as 25(OH)D less than 75 nmol/L. Ms. Dunn and colleagues quantified HLA-DRB1*15 alleles using allele-specific polymerase chain reaction amplification. Statistical analysis was performed using Spearman correlation models and Wilcoxon or Kruskal-Wallis tests as appropriate.

In all, 68 children were diagnosed with MS, 191 remained monophasic (monoADS). Approximately 46% of children with MS were HLA-DRB1*15-positive, compared with 29.9% of monoADS children. In addition, children with MS had significantly lower 25(OH)D levels (mean, 45.4 nmol/L) than monoADS children (mean, 61.9 nmol/L) at baseline. Non–sun-exposed skin tone measured in the upper inner arm did not differ between children diagnosed with MS (mean melanin index, 46.4) and monoADS (mean melanin index, 43.5). Furthermore, 25(OH)D levels correlated with upper inner arm melanin index in the MS group, but not in children with monoADS.

Ms. Dunn had nothing to disclose, but various coauthors have received compensation from companies such as Novartis, Merck, Teva, Celgene, and Genentech.
 

[email protected]

SOURCE: Dunn C et al. AAN 2019, Abstract S19.007.

PHILADELPHIA – Applying a criterion of three lesions with central vein signs distinguishes between multiple sclerosis and its mimics with high specificity and moderate sensitivity, according to research presented at the annual meeting of the American Academy of Neurology. Using this criterion in clinical practice is feasible, the researchers added.

Several years ago, researchers proposed the central vein sign as a specific and sensitive imaging biomarker for distinguishing between multiple sclerosis (MS) and its imaging mimics. Recent studies have proposed criteria for this distinction that are based on the proportion of lesions with the central vein sign. Criteria that are based on the absolute numbers of lesions with the central vein sign, however, may be more applicable in clinical practice, said Tim Sinnecker, MD, research associate at the University of Basel (Switzerland).


Dr. Sinnecker and colleagues conducted a multicenter study to evaluate the sensitivity and specificity of criteria that are based on the absolute numbers of lesions with the central vein sign (CVS) in distinguishing MS from non-MS conditions on clinical 3T brain MRI. They analyzed 606 participants with clinically isolated syndrome (CIS; n = 117), relapsing remitting MS (RRMS; n = 236, of whom 108 had a disease duration shorter than 5 years), aquaporin 4 antibody–positive neuromyelitis optica spectrum disorder (n = 32), systemic lupus erythematosus (n = 25), migraine (n = 29), cluster headache (n = 5), diabetes mellitus (n = 20), or other types of small-vessel disease (n = 142). Raters blinded to clinical data and lesion distribution determined the occurrence of CVS on 3T T2*-weighted or susceptibility-weighted imaging. The researchers assessed the sensitivity and specificity of different CVS lesion criteria that were defined according to the absolute numbers of lesions with CVS.


In total, Dr. Sinnecker and colleagues analyzed 4,447 lesions. The “two-CVS-lesions criterion” (two or more lesions with CVS) had a sensitivity and specificity of 76.2% and 79.3%, respectively, in distinguishing between RRMS/CIS and non-MS. The “three-CVS-lesions criterion” (three or more lesions with CVS) had a sensitivity and specificity of 61.9% and 89.0%, respectively. The observed sensitivity and specificity values were consistent across all disease subgroups examined in the study, including CIS and early RRMS. These results indicate that positive criteria based on CVS could be used to support the diagnosis of MS, Dr. Sinnecker said.

Dr. Sinnecker reported receiving personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion.

[email protected]

SOURCE: Sinnecker T et al. AAN 2019, Abstract S6.002.

PHILADELPHIA – Applying a criterion of three lesions with central vein signs distinguishes between multiple sclerosis and its mimics with high specificity and moderate sensitivity, according to research presented at the annual meeting of the American Academy of Neurology. Using this criterion in clinical practice is feasible, the researchers added.

Several years ago, researchers proposed the central vein sign as a specific and sensitive imaging biomarker for distinguishing between multiple sclerosis (MS) and its imaging mimics. Recent studies have proposed criteria for this distinction that are based on the proportion of lesions with the central vein sign. Criteria that are based on the absolute numbers of lesions with the central vein sign, however, may be more applicable in clinical practice, said Tim Sinnecker, MD, research associate at the University of Basel (Switzerland).


Dr. Sinnecker and colleagues conducted a multicenter study to evaluate the sensitivity and specificity of criteria that are based on the absolute numbers of lesions with the central vein sign (CVS) in distinguishing MS from non-MS conditions on clinical 3T brain MRI. They analyzed 606 participants with clinically isolated syndrome (CIS; n = 117), relapsing remitting MS (RRMS; n = 236, of whom 108 had a disease duration shorter than 5 years), aquaporin 4 antibody–positive neuromyelitis optica spectrum disorder (n = 32), systemic lupus erythematosus (n = 25), migraine (n = 29), cluster headache (n = 5), diabetes mellitus (n = 20), or other types of small-vessel disease (n = 142). Raters blinded to clinical data and lesion distribution determined the occurrence of CVS on 3T T2*-weighted or susceptibility-weighted imaging. The researchers assessed the sensitivity and specificity of different CVS lesion criteria that were defined according to the absolute numbers of lesions with CVS.


In total, Dr. Sinnecker and colleagues analyzed 4,447 lesions. The “two-CVS-lesions criterion” (two or more lesions with CVS) had a sensitivity and specificity of 76.2% and 79.3%, respectively, in distinguishing between RRMS/CIS and non-MS. The “three-CVS-lesions criterion” (three or more lesions with CVS) had a sensitivity and specificity of 61.9% and 89.0%, respectively. The observed sensitivity and specificity values were consistent across all disease subgroups examined in the study, including CIS and early RRMS. These results indicate that positive criteria based on CVS could be used to support the diagnosis of MS, Dr. Sinnecker said.

Dr. Sinnecker reported receiving personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion.

[email protected]

SOURCE: Sinnecker T et al. AAN 2019, Abstract S6.002.

PHILADELPHIA – Applying a criterion of three lesions with central vein signs distinguishes between multiple sclerosis and its mimics with high specificity and moderate sensitivity, according to research presented at the annual meeting of the American Academy of Neurology. Using this criterion in clinical practice is feasible, the researchers added.

Several years ago, researchers proposed the central vein sign as a specific and sensitive imaging biomarker for distinguishing between multiple sclerosis (MS) and its imaging mimics. Recent studies have proposed criteria for this distinction that are based on the proportion of lesions with the central vein sign. Criteria that are based on the absolute numbers of lesions with the central vein sign, however, may be more applicable in clinical practice, said Tim Sinnecker, MD, research associate at the University of Basel (Switzerland).


Dr. Sinnecker and colleagues conducted a multicenter study to evaluate the sensitivity and specificity of criteria that are based on the absolute numbers of lesions with the central vein sign (CVS) in distinguishing MS from non-MS conditions on clinical 3T brain MRI. They analyzed 606 participants with clinically isolated syndrome (CIS; n = 117), relapsing remitting MS (RRMS; n = 236, of whom 108 had a disease duration shorter than 5 years), aquaporin 4 antibody–positive neuromyelitis optica spectrum disorder (n = 32), systemic lupus erythematosus (n = 25), migraine (n = 29), cluster headache (n = 5), diabetes mellitus (n = 20), or other types of small-vessel disease (n = 142). Raters blinded to clinical data and lesion distribution determined the occurrence of CVS on 3T T2*-weighted or susceptibility-weighted imaging. The researchers assessed the sensitivity and specificity of different CVS lesion criteria that were defined according to the absolute numbers of lesions with CVS.


In total, Dr. Sinnecker and colleagues analyzed 4,447 lesions. The “two-CVS-lesions criterion” (two or more lesions with CVS) had a sensitivity and specificity of 76.2% and 79.3%, respectively, in distinguishing between RRMS/CIS and non-MS. The “three-CVS-lesions criterion” (three or more lesions with CVS) had a sensitivity and specificity of 61.9% and 89.0%, respectively. The observed sensitivity and specificity values were consistent across all disease subgroups examined in the study, including CIS and early RRMS. These results indicate that positive criteria based on CVS could be used to support the diagnosis of MS, Dr. Sinnecker said.

Dr. Sinnecker reported receiving personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion.

[email protected]

SOURCE: Sinnecker T et al. AAN 2019, Abstract S6.002.

PHILADELPHIA – Laquinimod appears not to improve motor function or clinical outcomes in patients with Huntington’s disease, according to a study presented at the annual meeting of the American Academy of Neurology. However, the drug reduced brain volume loss in the caudate and other regions.

Laquinimod is an investigational immunomodulatory drug that prevents inflammation and neurodegeneration in the CNS. The treatment was studied as a therapy for multiple sclerosis (MS), but development for this indication has been stopped. Researchers have observed that laquinimod modulates inflammatory pathways that are involved in Huntington’s disease pathology.

Ralf Reilmann, MD, PhD, founder of the George Huntington Institute and chair of the Huntington unit at the University of Münster (Germany), and colleagues conducted the phase 2 LEGATO-HD study at 48 sites in 10 countries to examine the efficacy and safety of laquinimod in patients with early Huntington’s disease. Participants were randomized in double-blind fashion to daily placebo or 0.5-mg, 1.0-mg, or 1.5-mg doses of laquinimod for 52 weeks. After the initiation of this trial, studies of the drug in MS indicated that the 1.5-mg dose was associated with cardiovascular risks, and Dr. Reilmann and his colleagues discontinued the 1.5-mg arm of their trial as a precaution.

The primary endpoint of LEGATO-HD was the change from baseline in the Unified Huntington’s Disease Rating Scale (UHDRS)–Total Motor Score (TMS). The secondary endpoint was the percent change in caudate volume at week 52 for the 1.0-mg dose group, compared with controls. The investigators also examined exploratory endpoints such as changes in MRI volume measures and Quantitative Motor, Clinician Interview-Based Impression of Change plus caregiver input, UHDRS–Total Functional Capacity and UHDRS–Functional Assessment scores. Adverse event reporting and clinical and laboratory examinations constituted the safety measures.

Dr. Reilmann and colleagues found no difference between the treated patients and controls in UHDRS-TMS. However, they did observe less caudate volume loss in the laquinimod group, compared with controls. All MRI exploratory measures also favored laquinimod. The researchers found no treatment effects of laquinimod in rater-dependent clinical outcome measures. Laquinimod was well tolerated, and the study yielded no new safety findings.

Dr. Reilmann has received research support from Teva, which supported the LEGATO-HD trial and in 2018 sold development and commercial rights for laquinimod to Active Biotech. He has received research support from a variety of other pharmaceutical companies and organizations, including the CHDI Foundation and the European Huntington Disease Network.

[email protected]

SOURCE: Reilmann R et al. AAN 2019, Abstract S16.007.

PHILADELPHIA – Laquinimod appears not to improve motor function or clinical outcomes in patients with Huntington’s disease, according to a study presented at the annual meeting of the American Academy of Neurology. However, the drug reduced brain volume loss in the caudate and other regions.

Laquinimod is an investigational immunomodulatory drug that prevents inflammation and neurodegeneration in the CNS. The treatment was studied as a therapy for multiple sclerosis (MS), but development for this indication has been stopped. Researchers have observed that laquinimod modulates inflammatory pathways that are involved in Huntington’s disease pathology.

Ralf Reilmann, MD, PhD, founder of the George Huntington Institute and chair of the Huntington unit at the University of Münster (Germany), and colleagues conducted the phase 2 LEGATO-HD study at 48 sites in 10 countries to examine the efficacy and safety of laquinimod in patients with early Huntington’s disease. Participants were randomized in double-blind fashion to daily placebo or 0.5-mg, 1.0-mg, or 1.5-mg doses of laquinimod for 52 weeks. After the initiation of this trial, studies of the drug in MS indicated that the 1.5-mg dose was associated with cardiovascular risks, and Dr. Reilmann and his colleagues discontinued the 1.5-mg arm of their trial as a precaution.

The primary endpoint of LEGATO-HD was the change from baseline in the Unified Huntington’s Disease Rating Scale (UHDRS)–Total Motor Score (TMS). The secondary endpoint was the percent change in caudate volume at week 52 for the 1.0-mg dose group, compared with controls. The investigators also examined exploratory endpoints such as changes in MRI volume measures and Quantitative Motor, Clinician Interview-Based Impression of Change plus caregiver input, UHDRS–Total Functional Capacity and UHDRS–Functional Assessment scores. Adverse event reporting and clinical and laboratory examinations constituted the safety measures.

Dr. Reilmann and colleagues found no difference between the treated patients and controls in UHDRS-TMS. However, they did observe less caudate volume loss in the laquinimod group, compared with controls. All MRI exploratory measures also favored laquinimod. The researchers found no treatment effects of laquinimod in rater-dependent clinical outcome measures. Laquinimod was well tolerated, and the study yielded no new safety findings.

Dr. Reilmann has received research support from Teva, which supported the LEGATO-HD trial and in 2018 sold development and commercial rights for laquinimod to Active Biotech. He has received research support from a variety of other pharmaceutical companies and organizations, including the CHDI Foundation and the European Huntington Disease Network.

[email protected]

SOURCE: Reilmann R et al. AAN 2019, Abstract S16.007.

PHILADELPHIA – Laquinimod appears not to improve motor function or clinical outcomes in patients with Huntington’s disease, according to a study presented at the annual meeting of the American Academy of Neurology. However, the drug reduced brain volume loss in the caudate and other regions.

Laquinimod is an investigational immunomodulatory drug that prevents inflammation and neurodegeneration in the CNS. The treatment was studied as a therapy for multiple sclerosis (MS), but development for this indication has been stopped. Researchers have observed that laquinimod modulates inflammatory pathways that are involved in Huntington’s disease pathology.

Ralf Reilmann, MD, PhD, founder of the George Huntington Institute and chair of the Huntington unit at the University of Münster (Germany), and colleagues conducted the phase 2 LEGATO-HD study at 48 sites in 10 countries to examine the efficacy and safety of laquinimod in patients with early Huntington’s disease. Participants were randomized in double-blind fashion to daily placebo or 0.5-mg, 1.0-mg, or 1.5-mg doses of laquinimod for 52 weeks. After the initiation of this trial, studies of the drug in MS indicated that the 1.5-mg dose was associated with cardiovascular risks, and Dr. Reilmann and his colleagues discontinued the 1.5-mg arm of their trial as a precaution.

The primary endpoint of LEGATO-HD was the change from baseline in the Unified Huntington’s Disease Rating Scale (UHDRS)–Total Motor Score (TMS). The secondary endpoint was the percent change in caudate volume at week 52 for the 1.0-mg dose group, compared with controls. The investigators also examined exploratory endpoints such as changes in MRI volume measures and Quantitative Motor, Clinician Interview-Based Impression of Change plus caregiver input, UHDRS–Total Functional Capacity and UHDRS–Functional Assessment scores. Adverse event reporting and clinical and laboratory examinations constituted the safety measures.

Dr. Reilmann and colleagues found no difference between the treated patients and controls in UHDRS-TMS. However, they did observe less caudate volume loss in the laquinimod group, compared with controls. All MRI exploratory measures also favored laquinimod. The researchers found no treatment effects of laquinimod in rater-dependent clinical outcome measures. Laquinimod was well tolerated, and the study yielded no new safety findings.

Dr. Reilmann has received research support from Teva, which supported the LEGATO-HD trial and in 2018 sold development and commercial rights for laquinimod to Active Biotech. He has received research support from a variety of other pharmaceutical companies and organizations, including the CHDI Foundation and the European Huntington Disease Network.

[email protected]

SOURCE: Reilmann R et al. AAN 2019, Abstract S16.007.

PHILADELPHIA – Oligomeric alpha synuclein levels in tears can help clinicians distinguish between patients with Parkinson’s disease and healthy controls, according to research presented at the annual meeting of the American Academy of Neurology. Chemokine (C-C motif) ligand 2 (CCL2), a cytokine, may be used for the same purpose, according to researchers.

Lacrimal glands have high numbers of cholinergic and other neurons. Parasympathetic and sympathetic neural pathways stimulate the tears that lacrimal grands secrete. It is possible that the production, packaging, and secretion of proteins into tears may alter when nerve function in the lacrimal glands and cornea changes. This idea may be tested by collecting reflex tears (i.e., stimulated tears provoked by an unanesthetized Schirmer’s test).

Mark Lew, MD, professor of clinical neurology at University of Southern California, Los Angeles, and colleagues previously studied patients using basal tears collected from an anesthetized Schirmer’s test. To examine whether the protein composition of reflex tears differs in patients with Parkinson’s disease, compared with healthy controls, they collected reflex tears from 85 patients with Parkinson’s disease and 80 age- and sex-matched healthy controls using an unanesthetized Schirmer’s test. The researchers pooled samples from both eyes to analyze alpha synuclein, CCL2, and total protein using enzyme-linked immunosorbent assays or multiplex ELISA.


Eligible participants were aged 30-85 years and had a Montreal Cognitive Assessment (MoCA) score of 21 or higher. Patients with Parkinson’s disease had a lower MoCA score than controls did, although it was still in the normal range. Tear flow was significantly decreased in patients with Parkinson’s disease, compared with controls.

Dr. Lew and colleagues found that the amount of oligomeric alpha synuclein was increased nearly 400% in the tears of patients with Parkinson’s disease, compared with those of healthy controls (4.21 ng/mg tear protein vs. 0.90 ng/mg tear protein). This difference was statistically significant. Similarly, CCL2 was significantly increased in the tears of patients with Parkinson’s disease, compared with those of healthy controls (165.8 pg/mg tear protein vs. 116.3 pg/mg tear protein). Among men, Parkinson’s disease was associated with greater rises in oligomeric alpha synuclein (4.95 ng/mg tear protein vs. 0.89 ng/mg tear protein in healthy controls) and CCL2 (201.5 pg/mg tear protein vs. 117.9 pg/mg tear protein in healthy controls) than in women. The origin of sex differences in these biomarker values requires further study, the investigators said.

Dr. Lew reported receiving research support from the Parkinson’s Study Group, the Michael J. Fox Foundation, Biotie Therapies, NeuroDerm, Enterin, Pharm2B Fellowship Grants, Allergan, and Medtronic.

[email protected]

SOURCE: Lew M et al. AAN 2019, Abstract S10.001

PHILADELPHIA – Oligomeric alpha synuclein levels in tears can help clinicians distinguish between patients with Parkinson’s disease and healthy controls, according to research presented at the annual meeting of the American Academy of Neurology. Chemokine (C-C motif) ligand 2 (CCL2), a cytokine, may be used for the same purpose, according to researchers.

Lacrimal glands have high numbers of cholinergic and other neurons. Parasympathetic and sympathetic neural pathways stimulate the tears that lacrimal grands secrete. It is possible that the production, packaging, and secretion of proteins into tears may alter when nerve function in the lacrimal glands and cornea changes. This idea may be tested by collecting reflex tears (i.e., stimulated tears provoked by an unanesthetized Schirmer’s test).

Mark Lew, MD, professor of clinical neurology at University of Southern California, Los Angeles, and colleagues previously studied patients using basal tears collected from an anesthetized Schirmer’s test. To examine whether the protein composition of reflex tears differs in patients with Parkinson’s disease, compared with healthy controls, they collected reflex tears from 85 patients with Parkinson’s disease and 80 age- and sex-matched healthy controls using an unanesthetized Schirmer’s test. The researchers pooled samples from both eyes to analyze alpha synuclein, CCL2, and total protein using enzyme-linked immunosorbent assays or multiplex ELISA.


Eligible participants were aged 30-85 years and had a Montreal Cognitive Assessment (MoCA) score of 21 or higher. Patients with Parkinson’s disease had a lower MoCA score than controls did, although it was still in the normal range. Tear flow was significantly decreased in patients with Parkinson’s disease, compared with controls.

Dr. Lew and colleagues found that the amount of oligomeric alpha synuclein was increased nearly 400% in the tears of patients with Parkinson’s disease, compared with those of healthy controls (4.21 ng/mg tear protein vs. 0.90 ng/mg tear protein). This difference was statistically significant. Similarly, CCL2 was significantly increased in the tears of patients with Parkinson’s disease, compared with those of healthy controls (165.8 pg/mg tear protein vs. 116.3 pg/mg tear protein). Among men, Parkinson’s disease was associated with greater rises in oligomeric alpha synuclein (4.95 ng/mg tear protein vs. 0.89 ng/mg tear protein in healthy controls) and CCL2 (201.5 pg/mg tear protein vs. 117.9 pg/mg tear protein in healthy controls) than in women. The origin of sex differences in these biomarker values requires further study, the investigators said.

Dr. Lew reported receiving research support from the Parkinson’s Study Group, the Michael J. Fox Foundation, Biotie Therapies, NeuroDerm, Enterin, Pharm2B Fellowship Grants, Allergan, and Medtronic.

[email protected]

SOURCE: Lew M et al. AAN 2019, Abstract S10.001

PHILADELPHIA – Oligomeric alpha synuclein levels in tears can help clinicians distinguish between patients with Parkinson’s disease and healthy controls, according to research presented at the annual meeting of the American Academy of Neurology. Chemokine (C-C motif) ligand 2 (CCL2), a cytokine, may be used for the same purpose, according to researchers.

Lacrimal glands have high numbers of cholinergic and other neurons. Parasympathetic and sympathetic neural pathways stimulate the tears that lacrimal grands secrete. It is possible that the production, packaging, and secretion of proteins into tears may alter when nerve function in the lacrimal glands and cornea changes. This idea may be tested by collecting reflex tears (i.e., stimulated tears provoked by an unanesthetized Schirmer’s test).

Mark Lew, MD, professor of clinical neurology at University of Southern California, Los Angeles, and colleagues previously studied patients using basal tears collected from an anesthetized Schirmer’s test. To examine whether the protein composition of reflex tears differs in patients with Parkinson’s disease, compared with healthy controls, they collected reflex tears from 85 patients with Parkinson’s disease and 80 age- and sex-matched healthy controls using an unanesthetized Schirmer’s test. The researchers pooled samples from both eyes to analyze alpha synuclein, CCL2, and total protein using enzyme-linked immunosorbent assays or multiplex ELISA.


Eligible participants were aged 30-85 years and had a Montreal Cognitive Assessment (MoCA) score of 21 or higher. Patients with Parkinson’s disease had a lower MoCA score than controls did, although it was still in the normal range. Tear flow was significantly decreased in patients with Parkinson’s disease, compared with controls.

Dr. Lew and colleagues found that the amount of oligomeric alpha synuclein was increased nearly 400% in the tears of patients with Parkinson’s disease, compared with those of healthy controls (4.21 ng/mg tear protein vs. 0.90 ng/mg tear protein). This difference was statistically significant. Similarly, CCL2 was significantly increased in the tears of patients with Parkinson’s disease, compared with those of healthy controls (165.8 pg/mg tear protein vs. 116.3 pg/mg tear protein). Among men, Parkinson’s disease was associated with greater rises in oligomeric alpha synuclein (4.95 ng/mg tear protein vs. 0.89 ng/mg tear protein in healthy controls) and CCL2 (201.5 pg/mg tear protein vs. 117.9 pg/mg tear protein in healthy controls) than in women. The origin of sex differences in these biomarker values requires further study, the investigators said.

Dr. Lew reported receiving research support from the Parkinson’s Study Group, the Michael J. Fox Foundation, Biotie Therapies, NeuroDerm, Enterin, Pharm2B Fellowship Grants, Allergan, and Medtronic.

[email protected]

SOURCE: Lew M et al. AAN 2019, Abstract S10.001

Levels of tau in cerebrospinal fluid (CSF) and plasma are significantly associated with survival time in patients with sporadic Creutzfeldt-Jakob disease, according to research published online ahead of print May 6 in JAMA Neurology. Levels of total tau in plasma and CSF are correlated, and plasma total tau is associated with survival time. These findings suggest that plasma total tau level could be a valid biomarker that guides clinical care for patients with sporadic Creutzfeldt-Jakob disease, said the investigators.

The accurate prediction of disease duration can assist clinicians and caregivers in clinical management, as well as influence the design of clinical trials. Previous studies have found that baseline protein levels in CSF and plasma are associated with disease duration in patients with sporadic Creutzfeldt-Jakob disease. To replicate these findings, Adam M. Staffaroni, PhD, of the department of neurology at the University of California, San Francisco, and colleagues conducted a longitudinal cohort study.
 

Evaluating fluid and nonfluid biomarkers

Dr. Staffaroni and colleagues recruited 193 participants with probable or definite sporadic Creutzfeldt-Jakob disease who had codon 129 genotyping and were referred to the UCSF Memory and Aging Center from March 2004 to January 2018. All participants underwent cognitive testing, informant measures, a neurologic examination, and CSF and blood sample collection. The researchers excluded from analysis five participants who had been placed on life-extending treatments. Participants were evaluated until death or censored at the time of statistical analysis.

Dr. Staffaroni and colleagues examined the following nonfluid biomarkers of survival: sex, age, codon 129 genotype, Barthel Index, and Medical Research Council (MRC) Prion Disease Rating Scale. In addition, they examined total tau level, phosphorylated tau level, total tau:phosphorylated tau ratio, neurofilament light (NfL) level, beta-amyloid 42 level, neuron-specific enolase level, 14-3-3 test result, and real-time quaking-induced conversion test in CSF as fluid biomarkers of survival. Finally, Dr. Staffaroni’s group analyzed total tau level, NfL level, and glial fibrillary acidic protein level in plasma as additional fluid biomarkers of survival.

The researchers fitted Cox proportional hazard models with time to event as the outcome. They log-transformed fluid biomarkers and ran models with and without nonfluid biomarkers of survival.

Plasma total tau was associated with survival

In all, 188 patients were included in the analysis. The population’s mean age was 63.8 years. Approximately 45% of participants were women. The diagnosis of sporadic Creutzfeldt-Jakob disease was pathologically confirmed for 78.2% of participants and probable for 21.8% of participants.

Dr. Staffaroni’s group observed strong correlations between plasma and CSF NfL concentrations and between plasma and CSF total tau concentrations. CSF total tau and CSF NfL concentrations were also correlated.

Among the nonfluid biomarkers, Barthel Index, MRC Scale, and codon 129 genotype were significantly associated with survival time. Lower level of function at baseline predicted a faster disease course.

Among the fluid biomarkers, greater levels of plasma total tau and NfL levels at baseline were associated with shorter survival. After the investigators controlled for Barthel Index and codon 129 genotype, the association of plasma total tau level with survival time remained significant. Plasma total tau level and Barthel Index (hazard ratio, 0.98) each independently predicted survival. Dr. Staffaroni and colleagues found that the hazard ratios for all CSF biomarkers were in the expected direction, and that those for total tau level, total tau:phosphorylated tau ratio, NfL level, and neuron-specific enolase level were statistically significant. Furthermore, positive results for 14-3-3 protein, neuron-specific enolase level, and total tau level were associated with a shorter time until death. Like the plasma biomarkers, CSF total tau level remained associated with survival after the investigators controlled for Barthel Index and codon 129 genotype. The same was true of CSF total tau:phosphorylated tau ratio, neuron-specific enolase level, and 14-3-3 result.
 

Plasma tau could be a diagnostic biomarker

“The hazard ratio associated with plasma total tau level was more than 40% higher than other fluid biomarkers of interest,” said the authors. “These findings further bolster the value of blood-based biomarkers, based on their minimally invasive and relatively inexpensive nature, and build on prior studies that suggested patients with sporadic Creutzfeldt-Jakob disease and controls can be discriminated with relatively high accuracy using blood-based assays.” When Dr. Staffaroni and colleagues modeled baseline functional status and plasma total tau levels together, they found that both were independent predictors of survival time. “This [finding] suggests that clinical measures and plasma total tau level could be combined to further improve prediction accuracy.”

Among the study’s limitations was its comparatively small subsample of patients for whom all plasma and CSF biomarkers were available. Disease duration and survival were longer in the study population than in the literature. “Another limitation is that the plasma biomarkers in this study, one of which showed great promise for predicting survival, were assayed using a research protocol,” said the researchers. “Widespread clinical use of these biomarkers will require well-validated commercial assays, development of which is underway.”

Before these biomarkers can be used in the clinic, these results will need to be replicated, and neurologists will need to develop consensus cutoffs for the biomarker levels. The researchers did not analyze plasma tau level as a diagnostic biomarker, but future studies should examine this potential, Dr. Staffaroni and colleagues concluded.

Grants from the National Institute on Aging and the National Institute of Allergy and Infectious Diseases supported the study.

[email protected]

SOURCE: Staffaroni AM et al. JAMA Neurol. 2019 May 6. doi: 10.1001/jamaneurol.2019.1071.

Levels of tau in cerebrospinal fluid (CSF) and plasma are significantly associated with survival time in patients with sporadic Creutzfeldt-Jakob disease, according to research published online ahead of print May 6 in JAMA Neurology. Levels of total tau in plasma and CSF are correlated, and plasma total tau is associated with survival time. These findings suggest that plasma total tau level could be a valid biomarker that guides clinical care for patients with sporadic Creutzfeldt-Jakob disease, said the investigators.

The accurate prediction of disease duration can assist clinicians and caregivers in clinical management, as well as influence the design of clinical trials. Previous studies have found that baseline protein levels in CSF and plasma are associated with disease duration in patients with sporadic Creutzfeldt-Jakob disease. To replicate these findings, Adam M. Staffaroni, PhD, of the department of neurology at the University of California, San Francisco, and colleagues conducted a longitudinal cohort study.
 

Evaluating fluid and nonfluid biomarkers

Dr. Staffaroni and colleagues recruited 193 participants with probable or definite sporadic Creutzfeldt-Jakob disease who had codon 129 genotyping and were referred to the UCSF Memory and Aging Center from March 2004 to January 2018. All participants underwent cognitive testing, informant measures, a neurologic examination, and CSF and blood sample collection. The researchers excluded from analysis five participants who had been placed on life-extending treatments. Participants were evaluated until death or censored at the time of statistical analysis.

Dr. Staffaroni and colleagues examined the following nonfluid biomarkers of survival: sex, age, codon 129 genotype, Barthel Index, and Medical Research Council (MRC) Prion Disease Rating Scale. In addition, they examined total tau level, phosphorylated tau level, total tau:phosphorylated tau ratio, neurofilament light (NfL) level, beta-amyloid 42 level, neuron-specific enolase level, 14-3-3 test result, and real-time quaking-induced conversion test in CSF as fluid biomarkers of survival. Finally, Dr. Staffaroni’s group analyzed total tau level, NfL level, and glial fibrillary acidic protein level in plasma as additional fluid biomarkers of survival.

The researchers fitted Cox proportional hazard models with time to event as the outcome. They log-transformed fluid biomarkers and ran models with and without nonfluid biomarkers of survival.

Plasma total tau was associated with survival

In all, 188 patients were included in the analysis. The population’s mean age was 63.8 years. Approximately 45% of participants were women. The diagnosis of sporadic Creutzfeldt-Jakob disease was pathologically confirmed for 78.2% of participants and probable for 21.8% of participants.

Dr. Staffaroni’s group observed strong correlations between plasma and CSF NfL concentrations and between plasma and CSF total tau concentrations. CSF total tau and CSF NfL concentrations were also correlated.

Among the nonfluid biomarkers, Barthel Index, MRC Scale, and codon 129 genotype were significantly associated with survival time. Lower level of function at baseline predicted a faster disease course.

Among the fluid biomarkers, greater levels of plasma total tau and NfL levels at baseline were associated with shorter survival. After the investigators controlled for Barthel Index and codon 129 genotype, the association of plasma total tau level with survival time remained significant. Plasma total tau level and Barthel Index (hazard ratio, 0.98) each independently predicted survival. Dr. Staffaroni and colleagues found that the hazard ratios for all CSF biomarkers were in the expected direction, and that those for total tau level, total tau:phosphorylated tau ratio, NfL level, and neuron-specific enolase level were statistically significant. Furthermore, positive results for 14-3-3 protein, neuron-specific enolase level, and total tau level were associated with a shorter time until death. Like the plasma biomarkers, CSF total tau level remained associated with survival after the investigators controlled for Barthel Index and codon 129 genotype. The same was true of CSF total tau:phosphorylated tau ratio, neuron-specific enolase level, and 14-3-3 result.
 

Plasma tau could be a diagnostic biomarker

“The hazard ratio associated with plasma total tau level was more than 40% higher than other fluid biomarkers of interest,” said the authors. “These findings further bolster the value of blood-based biomarkers, based on their minimally invasive and relatively inexpensive nature, and build on prior studies that suggested patients with sporadic Creutzfeldt-Jakob disease and controls can be discriminated with relatively high accuracy using blood-based assays.” When Dr. Staffaroni and colleagues modeled baseline functional status and plasma total tau levels together, they found that both were independent predictors of survival time. “This [finding] suggests that clinical measures and plasma total tau level could be combined to further improve prediction accuracy.”

Among the study’s limitations was its comparatively small subsample of patients for whom all plasma and CSF biomarkers were available. Disease duration and survival were longer in the study population than in the literature. “Another limitation is that the plasma biomarkers in this study, one of which showed great promise for predicting survival, were assayed using a research protocol,” said the researchers. “Widespread clinical use of these biomarkers will require well-validated commercial assays, development of which is underway.”

Before these biomarkers can be used in the clinic, these results will need to be replicated, and neurologists will need to develop consensus cutoffs for the biomarker levels. The researchers did not analyze plasma tau level as a diagnostic biomarker, but future studies should examine this potential, Dr. Staffaroni and colleagues concluded.

Grants from the National Institute on Aging and the National Institute of Allergy and Infectious Diseases supported the study.

[email protected]

SOURCE: Staffaroni AM et al. JAMA Neurol. 2019 May 6. doi: 10.1001/jamaneurol.2019.1071.

Levels of tau in cerebrospinal fluid (CSF) and plasma are significantly associated with survival time in patients with sporadic Creutzfeldt-Jakob disease, according to research published online ahead of print May 6 in JAMA Neurology. Levels of total tau in plasma and CSF are correlated, and plasma total tau is associated with survival time. These findings suggest that plasma total tau level could be a valid biomarker that guides clinical care for patients with sporadic Creutzfeldt-Jakob disease, said the investigators.

The accurate prediction of disease duration can assist clinicians and caregivers in clinical management, as well as influence the design of clinical trials. Previous studies have found that baseline protein levels in CSF and plasma are associated with disease duration in patients with sporadic Creutzfeldt-Jakob disease. To replicate these findings, Adam M. Staffaroni, PhD, of the department of neurology at the University of California, San Francisco, and colleagues conducted a longitudinal cohort study.
 

Evaluating fluid and nonfluid biomarkers

Dr. Staffaroni and colleagues recruited 193 participants with probable or definite sporadic Creutzfeldt-Jakob disease who had codon 129 genotyping and were referred to the UCSF Memory and Aging Center from March 2004 to January 2018. All participants underwent cognitive testing, informant measures, a neurologic examination, and CSF and blood sample collection. The researchers excluded from analysis five participants who had been placed on life-extending treatments. Participants were evaluated until death or censored at the time of statistical analysis.

Dr. Staffaroni and colleagues examined the following nonfluid biomarkers of survival: sex, age, codon 129 genotype, Barthel Index, and Medical Research Council (MRC) Prion Disease Rating Scale. In addition, they examined total tau level, phosphorylated tau level, total tau:phosphorylated tau ratio, neurofilament light (NfL) level, beta-amyloid 42 level, neuron-specific enolase level, 14-3-3 test result, and real-time quaking-induced conversion test in CSF as fluid biomarkers of survival. Finally, Dr. Staffaroni’s group analyzed total tau level, NfL level, and glial fibrillary acidic protein level in plasma as additional fluid biomarkers of survival.

The researchers fitted Cox proportional hazard models with time to event as the outcome. They log-transformed fluid biomarkers and ran models with and without nonfluid biomarkers of survival.

Plasma total tau was associated with survival

In all, 188 patients were included in the analysis. The population’s mean age was 63.8 years. Approximately 45% of participants were women. The diagnosis of sporadic Creutzfeldt-Jakob disease was pathologically confirmed for 78.2% of participants and probable for 21.8% of participants.

Dr. Staffaroni’s group observed strong correlations between plasma and CSF NfL concentrations and between plasma and CSF total tau concentrations. CSF total tau and CSF NfL concentrations were also correlated.

Among the nonfluid biomarkers, Barthel Index, MRC Scale, and codon 129 genotype were significantly associated with survival time. Lower level of function at baseline predicted a faster disease course.

Among the fluid biomarkers, greater levels of plasma total tau and NfL levels at baseline were associated with shorter survival. After the investigators controlled for Barthel Index and codon 129 genotype, the association of plasma total tau level with survival time remained significant. Plasma total tau level and Barthel Index (hazard ratio, 0.98) each independently predicted survival. Dr. Staffaroni and colleagues found that the hazard ratios for all CSF biomarkers were in the expected direction, and that those for total tau level, total tau:phosphorylated tau ratio, NfL level, and neuron-specific enolase level were statistically significant. Furthermore, positive results for 14-3-3 protein, neuron-specific enolase level, and total tau level were associated with a shorter time until death. Like the plasma biomarkers, CSF total tau level remained associated with survival after the investigators controlled for Barthel Index and codon 129 genotype. The same was true of CSF total tau:phosphorylated tau ratio, neuron-specific enolase level, and 14-3-3 result.
 

Plasma tau could be a diagnostic biomarker

“The hazard ratio associated with plasma total tau level was more than 40% higher than other fluid biomarkers of interest,” said the authors. “These findings further bolster the value of blood-based biomarkers, based on their minimally invasive and relatively inexpensive nature, and build on prior studies that suggested patients with sporadic Creutzfeldt-Jakob disease and controls can be discriminated with relatively high accuracy using blood-based assays.” When Dr. Staffaroni and colleagues modeled baseline functional status and plasma total tau levels together, they found that both were independent predictors of survival time. “This [finding] suggests that clinical measures and plasma total tau level could be combined to further improve prediction accuracy.”

Among the study’s limitations was its comparatively small subsample of patients for whom all plasma and CSF biomarkers were available. Disease duration and survival were longer in the study population than in the literature. “Another limitation is that the plasma biomarkers in this study, one of which showed great promise for predicting survival, were assayed using a research protocol,” said the researchers. “Widespread clinical use of these biomarkers will require well-validated commercial assays, development of which is underway.”

Before these biomarkers can be used in the clinic, these results will need to be replicated, and neurologists will need to develop consensus cutoffs for the biomarker levels. The researchers did not analyze plasma tau level as a diagnostic biomarker, but future studies should examine this potential, Dr. Staffaroni and colleagues concluded.

Grants from the National Institute on Aging and the National Institute of Allergy and Infectious Diseases supported the study.

[email protected]

SOURCE: Staffaroni AM et al. JAMA Neurol. 2019 May 6. doi: 10.1001/jamaneurol.2019.1071.

Cluster headache is associated with increased suicidality during the ictal and interictal periods, compared with the periods between bouts. Short- and long-term cluster headache disease burden, as well as depressive symptoms, contributes to suicidality, according to research published online Cephalalgia. Development of treatments that reduce the headache-related burden and prevent future bouts could reduce suicidality, said the researchers.

Although cluster headache has been called the “suicide headache,” few studies have examined suicidality in patients with cluster headache. Research by Rozen et al. found that the rate of suicidal attempt among patients was similar to that among the general population. The results have not been replicated, however, and the investigators did not examine whether suicidality varied according to the phases of the disorder.
 

A prospective, multicenter study

Mi Ji Lee, MD, PhD, clinical assistant professor of neurology at Samsung Medical Center in Seoul, South Korea, and colleagues conducted a prospective study to investigate the suicidality associated with cluster headache and the factors associated with increased suicidality in that disorder. The researchers enrolled 193 consecutive patients with cluster headache between September 2016 and August 2018 at 15 hospitals. They examined the patients and used the Patient Health Questionnaire–9 (PHQ-9) and the General Anxiety Disorder–7 item scale (GAD-7) screening tools. During the ictal and interictal phases, the researchers asked the patients whether they had had passive suicidal ideation, active suicidal ideation, suicidal planning, or suicidal attempt. Dr. Ji Lee and colleagues performed univariable and multivariable logistic regression analyses to evaluate the factors associated with high ictal suicidality, which was defined as two or more positive responses during the ictal phase. Participants were followed up during the between-bout phase.

The researchers excluded 18 patients from analysis because they were between bouts at enrollment. The mean age of the remaining 175 patients was 38.4 years. Mean age at onset was 29.9 years. About 85% of the patients were male. The diagnosis was definite cluster headache for 87.4% of the sample and probable cluster headache for 12.6%. In addition, 88% of the population had episodic cluster headache.
 

Suicidal ideation increased during the ictal phase

During the ictal phase, 64.2% of participants reported passive suicidal ideation, and 35.8% reported active suicidal ideation. Furthermore, 5.8% of patients had a suicidal plan, and 2.3% attempted suicide. In the interictal phase, 4.0% of patients reported passive suicidal ideation, and 3.5% reported active suicidal ideation. Interictal suicidal planning was reported by 2.9% of participants, and 1.2% of participants attempted suicide interictally. The results were similar between patients with definite and probable cluster headache.

The ictal phase increased the odds of passive suicidal ideation (odds ratio [OR], 42.46), active suicidal ideation (OR, 15.55), suicidal planning (OR, 2.06), and suicidal attempt (OR, 2.02), compared with the interictal phase. The differences in suicidal planning and suicidal attempt between the ictal and interictal phases, however, were not statistically significant.

Longer disease duration, higher attack intensity, higher Headache Impact Test–6 (HIT-6) score, GAD-7 score, and PHQ-9 score were associated with high ictal suicidality. Disease duration, HIT-6, and PHQ-9 remained significantly associated with high ictal suicidality in the multivariate analysis. Younger age at onset, longer disease duration, total number of lifetime bouts, and higher GAD-7 and PHQ-9 scores were significantly associated with interictal suicidality in the univariable analysis. The total number of lifetime bouts and the PHQ-9 scores remained significant in the multivariable analysis.

In all, 54 patients were followed up between bouts. None reported passive suicidal ideation, 1.9% reported active suicidal ideation, 1.9% reported suicidal planning, and none reported suicidal attempt. Compared with the between-bouts period, the ictal phase was associated with significantly higher odds of active suicidal ideation (OR, 37.32) and nonsignificantly increased suicidal planning (OR, 3.20).
 

Patients need a disease-modifying treatment

Taken together, the study results underscore the importance of proper management of cluster headache to reduce its burden, said the authors. “Given that greater headache-related impact was independently associated with ictal suicidality, an intensive treatment to reduce the headache-related impact might be beneficial to prevent suicide in cluster headache patients,” they said. In addition to reducing headache-related impact and headache intensity, “a disease-modifying treatment to prevent further bouts is warranted to decrease suicidality in cluster headache patients.”

Although patients with cluster headache had increased suicidality in the ictal and interictal phases, they had lower suicidality between bouts, compared with the general population. This result suggests that patients remain mentally healthy when the bouts are over, and that “a strategy to shorten the length of bout is warranted,” said Dr. Ji Lee and colleagues. Furthermore, the fact that suicidality did not differ significantly between patients with definite cluster headache and those with probable cluster headache “prompts clinicians for an increased identification and intensive treatment strategy for probable cluster headache.”

The current study is the first prospective investigation of suicidality in the various phases of cluster headache, according to the investigators. It nevertheless has several limitations. The prevalence of chronic cluster headache was low in the study population, and not all patients presented for follow-up during the period between bouts. In addition, the data were obtained from recall, and consequently may be less accurate than those gained from prospective recording. Finally, Dr. Ji Lee and colleagues did not gather information on personality disorders, insomnia, substance abuse, or addiction, even though these factors can influence suicidality in patients with chronic pain.

The investigators reported no conflicts of interest related to their research. The study was supported by a grant from the Korean Neurological Association.

[email protected]

SOURCE: Ji Lee M et al. Cephalalgia. 2019 Apr 24. doi: 10.1177/0333102419845660.

Cluster headache is associated with increased suicidality during the ictal and interictal periods, compared with the periods between bouts. Short- and long-term cluster headache disease burden, as well as depressive symptoms, contributes to suicidality, according to research published online Cephalalgia. Development of treatments that reduce the headache-related burden and prevent future bouts could reduce suicidality, said the researchers.

Although cluster headache has been called the “suicide headache,” few studies have examined suicidality in patients with cluster headache. Research by Rozen et al. found that the rate of suicidal attempt among patients was similar to that among the general population. The results have not been replicated, however, and the investigators did not examine whether suicidality varied according to the phases of the disorder.
 

A prospective, multicenter study

Mi Ji Lee, MD, PhD, clinical assistant professor of neurology at Samsung Medical Center in Seoul, South Korea, and colleagues conducted a prospective study to investigate the suicidality associated with cluster headache and the factors associated with increased suicidality in that disorder. The researchers enrolled 193 consecutive patients with cluster headache between September 2016 and August 2018 at 15 hospitals. They examined the patients and used the Patient Health Questionnaire–9 (PHQ-9) and the General Anxiety Disorder–7 item scale (GAD-7) screening tools. During the ictal and interictal phases, the researchers asked the patients whether they had had passive suicidal ideation, active suicidal ideation, suicidal planning, or suicidal attempt. Dr. Ji Lee and colleagues performed univariable and multivariable logistic regression analyses to evaluate the factors associated with high ictal suicidality, which was defined as two or more positive responses during the ictal phase. Participants were followed up during the between-bout phase.

The researchers excluded 18 patients from analysis because they were between bouts at enrollment. The mean age of the remaining 175 patients was 38.4 years. Mean age at onset was 29.9 years. About 85% of the patients were male. The diagnosis was definite cluster headache for 87.4% of the sample and probable cluster headache for 12.6%. In addition, 88% of the population had episodic cluster headache.
 

Suicidal ideation increased during the ictal phase

During the ictal phase, 64.2% of participants reported passive suicidal ideation, and 35.8% reported active suicidal ideation. Furthermore, 5.8% of patients had a suicidal plan, and 2.3% attempted suicide. In the interictal phase, 4.0% of patients reported passive suicidal ideation, and 3.5% reported active suicidal ideation. Interictal suicidal planning was reported by 2.9% of participants, and 1.2% of participants attempted suicide interictally. The results were similar between patients with definite and probable cluster headache.

The ictal phase increased the odds of passive suicidal ideation (odds ratio [OR], 42.46), active suicidal ideation (OR, 15.55), suicidal planning (OR, 2.06), and suicidal attempt (OR, 2.02), compared with the interictal phase. The differences in suicidal planning and suicidal attempt between the ictal and interictal phases, however, were not statistically significant.

Longer disease duration, higher attack intensity, higher Headache Impact Test–6 (HIT-6) score, GAD-7 score, and PHQ-9 score were associated with high ictal suicidality. Disease duration, HIT-6, and PHQ-9 remained significantly associated with high ictal suicidality in the multivariate analysis. Younger age at onset, longer disease duration, total number of lifetime bouts, and higher GAD-7 and PHQ-9 scores were significantly associated with interictal suicidality in the univariable analysis. The total number of lifetime bouts and the PHQ-9 scores remained significant in the multivariable analysis.

In all, 54 patients were followed up between bouts. None reported passive suicidal ideation, 1.9% reported active suicidal ideation, 1.9% reported suicidal planning, and none reported suicidal attempt. Compared with the between-bouts period, the ictal phase was associated with significantly higher odds of active suicidal ideation (OR, 37.32) and nonsignificantly increased suicidal planning (OR, 3.20).
 

Patients need a disease-modifying treatment

Taken together, the study results underscore the importance of proper management of cluster headache to reduce its burden, said the authors. “Given that greater headache-related impact was independently associated with ictal suicidality, an intensive treatment to reduce the headache-related impact might be beneficial to prevent suicide in cluster headache patients,” they said. In addition to reducing headache-related impact and headache intensity, “a disease-modifying treatment to prevent further bouts is warranted to decrease suicidality in cluster headache patients.”

Although patients with cluster headache had increased suicidality in the ictal and interictal phases, they had lower suicidality between bouts, compared with the general population. This result suggests that patients remain mentally healthy when the bouts are over, and that “a strategy to shorten the length of bout is warranted,” said Dr. Ji Lee and colleagues. Furthermore, the fact that suicidality did not differ significantly between patients with definite cluster headache and those with probable cluster headache “prompts clinicians for an increased identification and intensive treatment strategy for probable cluster headache.”

The current study is the first prospective investigation of suicidality in the various phases of cluster headache, according to the investigators. It nevertheless has several limitations. The prevalence of chronic cluster headache was low in the study population, and not all patients presented for follow-up during the period between bouts. In addition, the data were obtained from recall, and consequently may be less accurate than those gained from prospective recording. Finally, Dr. Ji Lee and colleagues did not gather information on personality disorders, insomnia, substance abuse, or addiction, even though these factors can influence suicidality in patients with chronic pain.

The investigators reported no conflicts of interest related to their research. The study was supported by a grant from the Korean Neurological Association.

[email protected]

SOURCE: Ji Lee M et al. Cephalalgia. 2019 Apr 24. doi: 10.1177/0333102419845660.

Cluster headache is associated with increased suicidality during the ictal and interictal periods, compared with the periods between bouts. Short- and long-term cluster headache disease burden, as well as depressive symptoms, contributes to suicidality, according to research published online Cephalalgia. Development of treatments that reduce the headache-related burden and prevent future bouts could reduce suicidality, said the researchers.

Although cluster headache has been called the “suicide headache,” few studies have examined suicidality in patients with cluster headache. Research by Rozen et al. found that the rate of suicidal attempt among patients was similar to that among the general population. The results have not been replicated, however, and the investigators did not examine whether suicidality varied according to the phases of the disorder.
 

A prospective, multicenter study

Mi Ji Lee, MD, PhD, clinical assistant professor of neurology at Samsung Medical Center in Seoul, South Korea, and colleagues conducted a prospective study to investigate the suicidality associated with cluster headache and the factors associated with increased suicidality in that disorder. The researchers enrolled 193 consecutive patients with cluster headache between September 2016 and August 2018 at 15 hospitals. They examined the patients and used the Patient Health Questionnaire–9 (PHQ-9) and the General Anxiety Disorder–7 item scale (GAD-7) screening tools. During the ictal and interictal phases, the researchers asked the patients whether they had had passive suicidal ideation, active suicidal ideation, suicidal planning, or suicidal attempt. Dr. Ji Lee and colleagues performed univariable and multivariable logistic regression analyses to evaluate the factors associated with high ictal suicidality, which was defined as two or more positive responses during the ictal phase. Participants were followed up during the between-bout phase.

The researchers excluded 18 patients from analysis because they were between bouts at enrollment. The mean age of the remaining 175 patients was 38.4 years. Mean age at onset was 29.9 years. About 85% of the patients were male. The diagnosis was definite cluster headache for 87.4% of the sample and probable cluster headache for 12.6%. In addition, 88% of the population had episodic cluster headache.
 

Suicidal ideation increased during the ictal phase

During the ictal phase, 64.2% of participants reported passive suicidal ideation, and 35.8% reported active suicidal ideation. Furthermore, 5.8% of patients had a suicidal plan, and 2.3% attempted suicide. In the interictal phase, 4.0% of patients reported passive suicidal ideation, and 3.5% reported active suicidal ideation. Interictal suicidal planning was reported by 2.9% of participants, and 1.2% of participants attempted suicide interictally. The results were similar between patients with definite and probable cluster headache.

The ictal phase increased the odds of passive suicidal ideation (odds ratio [OR], 42.46), active suicidal ideation (OR, 15.55), suicidal planning (OR, 2.06), and suicidal attempt (OR, 2.02), compared with the interictal phase. The differences in suicidal planning and suicidal attempt between the ictal and interictal phases, however, were not statistically significant.

Longer disease duration, higher attack intensity, higher Headache Impact Test–6 (HIT-6) score, GAD-7 score, and PHQ-9 score were associated with high ictal suicidality. Disease duration, HIT-6, and PHQ-9 remained significantly associated with high ictal suicidality in the multivariate analysis. Younger age at onset, longer disease duration, total number of lifetime bouts, and higher GAD-7 and PHQ-9 scores were significantly associated with interictal suicidality in the univariable analysis. The total number of lifetime bouts and the PHQ-9 scores remained significant in the multivariable analysis.

In all, 54 patients were followed up between bouts. None reported passive suicidal ideation, 1.9% reported active suicidal ideation, 1.9% reported suicidal planning, and none reported suicidal attempt. Compared with the between-bouts period, the ictal phase was associated with significantly higher odds of active suicidal ideation (OR, 37.32) and nonsignificantly increased suicidal planning (OR, 3.20).
 

Patients need a disease-modifying treatment

Taken together, the study results underscore the importance of proper management of cluster headache to reduce its burden, said the authors. “Given that greater headache-related impact was independently associated with ictal suicidality, an intensive treatment to reduce the headache-related impact might be beneficial to prevent suicide in cluster headache patients,” they said. In addition to reducing headache-related impact and headache intensity, “a disease-modifying treatment to prevent further bouts is warranted to decrease suicidality in cluster headache patients.”

Although patients with cluster headache had increased suicidality in the ictal and interictal phases, they had lower suicidality between bouts, compared with the general population. This result suggests that patients remain mentally healthy when the bouts are over, and that “a strategy to shorten the length of bout is warranted,” said Dr. Ji Lee and colleagues. Furthermore, the fact that suicidality did not differ significantly between patients with definite cluster headache and those with probable cluster headache “prompts clinicians for an increased identification and intensive treatment strategy for probable cluster headache.”

The current study is the first prospective investigation of suicidality in the various phases of cluster headache, according to the investigators. It nevertheless has several limitations. The prevalence of chronic cluster headache was low in the study population, and not all patients presented for follow-up during the period between bouts. In addition, the data were obtained from recall, and consequently may be less accurate than those gained from prospective recording. Finally, Dr. Ji Lee and colleagues did not gather information on personality disorders, insomnia, substance abuse, or addiction, even though these factors can influence suicidality in patients with chronic pain.

The investigators reported no conflicts of interest related to their research. The study was supported by a grant from the Korean Neurological Association.

[email protected]

SOURCE: Ji Lee M et al. Cephalalgia. 2019 Apr 24. doi: 10.1177/0333102419845660.

PHILADELPHIA – Witnessed apneas during sleep are associated with increased tau accumulation in the entorhinal cortex, according to data that will be presented at the annual meeting of the American Academy of Neurology. Tau accumulation is a biomarker of Alzheimer’s disease, and the finding suggests a possible explanation for the apparent association between sleep disruption and dementia.

“Our research results raise the possibility that sleep apnea affects tau accumulation,” said Diego Z. Carvalho, MD, of the Mayo Clinic in Rochester, Minn., in a press release. “But it is also possible that higher levels of tau in other regions may predispose a person to sleep apnea, so longer studies are now needed to solve this chicken-and-egg problem.”

Previous research had suggested an association between sleep disruption and increased risk of dementia. Obstructive sleep apnea in particular has been associated with this increased risk. The pathological processes that account for this association are unknown, however.

Dr. Carvalho and colleagues decided to evaluate whether apneas during sleep, reported by the patient or an informant, were associated with high levels of tau in cognitively normal elderly individuals. The investigators identified 288 participants in the Mayo Clinic Study of Aging for their analysis. Eligible participants were aged 65 years or older, had no cognitive impairment, had undergone tau PET and amyloid PET scans, and had completed a questionnaire that solicited information about witnessed apneas during sleep (either from patients or bed partners). Dr. Carvalho’s group took the entorhinal cortex as its region of interest because it is highly susceptible to tau accumulation. The entorhinal cortex is involved in memory, navigation, and the perception of time. They chose the cerebellum crus as their reference region.

The investigators created a linear model to evaluate the association between tau in the entorhinal cortex and witnessed apneas. They controlled the data for age, sex, years of education, body mass index, hypertension, hyperlipidemia, diabetes, reduced sleep, excessive daytime sleepiness, and global amyloid.

In all, 43 participants (15%) had witnessed apneas during sleep. Witnessed apneas were significantly associated with tau in the entorhinal cortex. After controlling for potential confounders, Dr. Carvalho and colleagues estimated a 0.049 elevation in the entorhinal cortex tau standardized uptake value ratio (95% confidence interval, 0.011–0.087; P = 0.012).

The study had a relatively small sample size, and its results require validation. Other important limitations include the absence of sleep studies to confirm the presence and severity of sleep apnea and a lack of information about whether participants already were receiving treatment for sleep apnea.

The National Institutes of Health supported the study.
 

[email protected]

SOURCE: Carvalho D et al. AAN 2019, Abstract P3.6-021.

PHILADELPHIA – Witnessed apneas during sleep are associated with increased tau accumulation in the entorhinal cortex, according to data that will be presented at the annual meeting of the American Academy of Neurology. Tau accumulation is a biomarker of Alzheimer’s disease, and the finding suggests a possible explanation for the apparent association between sleep disruption and dementia.

“Our research results raise the possibility that sleep apnea affects tau accumulation,” said Diego Z. Carvalho, MD, of the Mayo Clinic in Rochester, Minn., in a press release. “But it is also possible that higher levels of tau in other regions may predispose a person to sleep apnea, so longer studies are now needed to solve this chicken-and-egg problem.”

Previous research had suggested an association between sleep disruption and increased risk of dementia. Obstructive sleep apnea in particular has been associated with this increased risk. The pathological processes that account for this association are unknown, however.

Dr. Carvalho and colleagues decided to evaluate whether apneas during sleep, reported by the patient or an informant, were associated with high levels of tau in cognitively normal elderly individuals. The investigators identified 288 participants in the Mayo Clinic Study of Aging for their analysis. Eligible participants were aged 65 years or older, had no cognitive impairment, had undergone tau PET and amyloid PET scans, and had completed a questionnaire that solicited information about witnessed apneas during sleep (either from patients or bed partners). Dr. Carvalho’s group took the entorhinal cortex as its region of interest because it is highly susceptible to tau accumulation. The entorhinal cortex is involved in memory, navigation, and the perception of time. They chose the cerebellum crus as their reference region.

The investigators created a linear model to evaluate the association between tau in the entorhinal cortex and witnessed apneas. They controlled the data for age, sex, years of education, body mass index, hypertension, hyperlipidemia, diabetes, reduced sleep, excessive daytime sleepiness, and global amyloid.

In all, 43 participants (15%) had witnessed apneas during sleep. Witnessed apneas were significantly associated with tau in the entorhinal cortex. After controlling for potential confounders, Dr. Carvalho and colleagues estimated a 0.049 elevation in the entorhinal cortex tau standardized uptake value ratio (95% confidence interval, 0.011–0.087; P = 0.012).

The study had a relatively small sample size, and its results require validation. Other important limitations include the absence of sleep studies to confirm the presence and severity of sleep apnea and a lack of information about whether participants already were receiving treatment for sleep apnea.

The National Institutes of Health supported the study.
 

[email protected]

SOURCE: Carvalho D et al. AAN 2019, Abstract P3.6-021.

PHILADELPHIA – Witnessed apneas during sleep are associated with increased tau accumulation in the entorhinal cortex, according to data that will be presented at the annual meeting of the American Academy of Neurology. Tau accumulation is a biomarker of Alzheimer’s disease, and the finding suggests a possible explanation for the apparent association between sleep disruption and dementia.

“Our research results raise the possibility that sleep apnea affects tau accumulation,” said Diego Z. Carvalho, MD, of the Mayo Clinic in Rochester, Minn., in a press release. “But it is also possible that higher levels of tau in other regions may predispose a person to sleep apnea, so longer studies are now needed to solve this chicken-and-egg problem.”

Previous research had suggested an association between sleep disruption and increased risk of dementia. Obstructive sleep apnea in particular has been associated with this increased risk. The pathological processes that account for this association are unknown, however.

Dr. Carvalho and colleagues decided to evaluate whether apneas during sleep, reported by the patient or an informant, were associated with high levels of tau in cognitively normal elderly individuals. The investigators identified 288 participants in the Mayo Clinic Study of Aging for their analysis. Eligible participants were aged 65 years or older, had no cognitive impairment, had undergone tau PET and amyloid PET scans, and had completed a questionnaire that solicited information about witnessed apneas during sleep (either from patients or bed partners). Dr. Carvalho’s group took the entorhinal cortex as its region of interest because it is highly susceptible to tau accumulation. The entorhinal cortex is involved in memory, navigation, and the perception of time. They chose the cerebellum crus as their reference region.

The investigators created a linear model to evaluate the association between tau in the entorhinal cortex and witnessed apneas. They controlled the data for age, sex, years of education, body mass index, hypertension, hyperlipidemia, diabetes, reduced sleep, excessive daytime sleepiness, and global amyloid.

In all, 43 participants (15%) had witnessed apneas during sleep. Witnessed apneas were significantly associated with tau in the entorhinal cortex. After controlling for potential confounders, Dr. Carvalho and colleagues estimated a 0.049 elevation in the entorhinal cortex tau standardized uptake value ratio (95% confidence interval, 0.011–0.087; P = 0.012).

The study had a relatively small sample size, and its results require validation. Other important limitations include the absence of sleep studies to confirm the presence and severity of sleep apnea and a lack of information about whether participants already were receiving treatment for sleep apnea.

The National Institutes of Health supported the study.
 

[email protected]

SOURCE: Carvalho D et al. AAN 2019, Abstract P3.6-021.

High body mass index (BMI) is associated with reduced mortality and reduced disability after acute ischemic stroke, according to research that will be presented at the annual meeting of the American Academy of Neurology.

“One possible explanation is that people who are overweight or obese may have a nutritional reserve that may help them survive during prolonged illness,” said Zuolu Liu, MD, of the University of California, Los Angeles, in a press release. “More research is needed to investigate the relationship between BMI and stroke.”

The obesity paradox was first noted when studies suggested that being overweight improved survival in patients with kidney disease or heart disease. Investigators previously examined whether the obesity paradox is observed in stroke, but their studies were underpowered and produced ambiguous results.

Dr. Liu and colleagues sought to evaluate the relationship between BMI and 90-day outcomes of acute ischemic stroke. They examined data for all participants in the FAST-MAG trial, which studied whether prehospital treatment with magnesium improved disability outcomes of acute ischemic stroke. Dr. Liu and colleagues focused on the outcomes of death, disability or death (that is, modified Rankin Scale score of 2-6), and low stroke-related quality of life (that is, Stroke Impact Scale score less than 70). They analyzed potential relationships with BMI univariately and in multivariate models that adjusted for 12 prognostic variables, such as high blood pressure, high cholesterol, and smoking.

Dr. Liu’s group included 1,033 participants in its study. The population’s mean age was 71 years, and 45.1% of the population was female. Mean National Institutes of Health Stroke Scale (NIHSS) score was 10.6, and mean BMI was 27.5 kg/m².

The investigators found an inverse association between the risk of death and BMI. Adjusted odds ratios for mortality were 1.67 for underweight participants, 0.85 for overweight participants, 0.54 for obese participants, and 0.38 for severely obese participants, compared with participants of normal weight. Similarly, the risk of disability had a U-shaped relationship with BMI. Odds ratios for disability or death were 1.19 for underweight participants, 0.78 for overweight participants, 0.72 for obese participants, and 0.96 for severely obese participants, compared with participants of normal weight. This relationship was attenuated after adjustment for other prognostic factors, however. Dr. Liu’s group did not find a significant association between BMI and low stroke-related quality of life.

The study was limited by the fact that all participants were from Southern California, which potentially reduced the generalizability of the results. The racial and ethnic composition of the study population, however, is similar to that of the national population, said the researchers.

No study sponsor was reported.
 

[email protected]

SOURCE: Liu Z et al. AAN 2019, Abstract P3.3-01.

High body mass index (BMI) is associated with reduced mortality and reduced disability after acute ischemic stroke, according to research that will be presented at the annual meeting of the American Academy of Neurology.

“One possible explanation is that people who are overweight or obese may have a nutritional reserve that may help them survive during prolonged illness,” said Zuolu Liu, MD, of the University of California, Los Angeles, in a press release. “More research is needed to investigate the relationship between BMI and stroke.”

The obesity paradox was first noted when studies suggested that being overweight improved survival in patients with kidney disease or heart disease. Investigators previously examined whether the obesity paradox is observed in stroke, but their studies were underpowered and produced ambiguous results.

Dr. Liu and colleagues sought to evaluate the relationship between BMI and 90-day outcomes of acute ischemic stroke. They examined data for all participants in the FAST-MAG trial, which studied whether prehospital treatment with magnesium improved disability outcomes of acute ischemic stroke. Dr. Liu and colleagues focused on the outcomes of death, disability or death (that is, modified Rankin Scale score of 2-6), and low stroke-related quality of life (that is, Stroke Impact Scale score less than 70). They analyzed potential relationships with BMI univariately and in multivariate models that adjusted for 12 prognostic variables, such as high blood pressure, high cholesterol, and smoking.

Dr. Liu’s group included 1,033 participants in its study. The population’s mean age was 71 years, and 45.1% of the population was female. Mean National Institutes of Health Stroke Scale (NIHSS) score was 10.6, and mean BMI was 27.5 kg/m².

The investigators found an inverse association between the risk of death and BMI. Adjusted odds ratios for mortality were 1.67 for underweight participants, 0.85 for overweight participants, 0.54 for obese participants, and 0.38 for severely obese participants, compared with participants of normal weight. Similarly, the risk of disability had a U-shaped relationship with BMI. Odds ratios for disability or death were 1.19 for underweight participants, 0.78 for overweight participants, 0.72 for obese participants, and 0.96 for severely obese participants, compared with participants of normal weight. This relationship was attenuated after adjustment for other prognostic factors, however. Dr. Liu’s group did not find a significant association between BMI and low stroke-related quality of life.

The study was limited by the fact that all participants were from Southern California, which potentially reduced the generalizability of the results. The racial and ethnic composition of the study population, however, is similar to that of the national population, said the researchers.

No study sponsor was reported.
 

[email protected]

SOURCE: Liu Z et al. AAN 2019, Abstract P3.3-01.

High body mass index (BMI) is associated with reduced mortality and reduced disability after acute ischemic stroke, according to research that will be presented at the annual meeting of the American Academy of Neurology.

“One possible explanation is that people who are overweight or obese may have a nutritional reserve that may help them survive during prolonged illness,” said Zuolu Liu, MD, of the University of California, Los Angeles, in a press release. “More research is needed to investigate the relationship between BMI and stroke.”

The obesity paradox was first noted when studies suggested that being overweight improved survival in patients with kidney disease or heart disease. Investigators previously examined whether the obesity paradox is observed in stroke, but their studies were underpowered and produced ambiguous results.

Dr. Liu and colleagues sought to evaluate the relationship between BMI and 90-day outcomes of acute ischemic stroke. They examined data for all participants in the FAST-MAG trial, which studied whether prehospital treatment with magnesium improved disability outcomes of acute ischemic stroke. Dr. Liu and colleagues focused on the outcomes of death, disability or death (that is, modified Rankin Scale score of 2-6), and low stroke-related quality of life (that is, Stroke Impact Scale score less than 70). They analyzed potential relationships with BMI univariately and in multivariate models that adjusted for 12 prognostic variables, such as high blood pressure, high cholesterol, and smoking.

Dr. Liu’s group included 1,033 participants in its study. The population’s mean age was 71 years, and 45.1% of the population was female. Mean National Institutes of Health Stroke Scale (NIHSS) score was 10.6, and mean BMI was 27.5 kg/m².

The investigators found an inverse association between the risk of death and BMI. Adjusted odds ratios for mortality were 1.67 for underweight participants, 0.85 for overweight participants, 0.54 for obese participants, and 0.38 for severely obese participants, compared with participants of normal weight. Similarly, the risk of disability had a U-shaped relationship with BMI. Odds ratios for disability or death were 1.19 for underweight participants, 0.78 for overweight participants, 0.72 for obese participants, and 0.96 for severely obese participants, compared with participants of normal weight. This relationship was attenuated after adjustment for other prognostic factors, however. Dr. Liu’s group did not find a significant association between BMI and low stroke-related quality of life.

The study was limited by the fact that all participants were from Southern California, which potentially reduced the generalizability of the results. The racial and ethnic composition of the study population, however, is similar to that of the national population, said the researchers.

No study sponsor was reported.
 

[email protected]

SOURCE: Liu Z et al. AAN 2019, Abstract P3.3-01.

WASHINGTON – The prescription of oral antibiotics after benign excisions, malignant excisions, and Mohs surgery has increased over the past decade, according to an analysis presented at the annual meeting of the American Academy of Dermatology.

John Barbieri, MD, a dermatologist and postdoctoral research fellow at the University of Pennsylvania, Philadelphia, who presented the results, and colleagues examined data about antibiotic use in dermatology between 2008 and 2016. Overall, antibiotic use decreased during this period, primarily for chronic conditions such as acne and rosacea. On the other hand, antibiotic use associated with surgical visits increased by approximately 70%.

Using data from 2008 to 2016 in the Optum Clinformatics DataMart deidentified commercial claims database, the researchers performed a repeated cross-sectional analysis of oral antibiotic prescriptions associated with encounters for surgical procedures performed by dermatologists. They found that oral antibiotic prescriptions increased from 2.9% to 4.4% of visits for benign excisions, from 4.2% to 6.3% of visits for malignant excisions, and from 9.9% to 13.8% of visits for Mohs procedures during this time period. Oral antibiotic prescribing was more common for procedures that entailed a flap or graft and among patients with diabetes, female patients, and younger patients.


The investigators observed greater than twofold variation in antibiotic-prescribing rates across geographic census divisions. “If higher-prescribing divisions were to develop antibiotic prescribing rates similar to [those of] lower-prescribing divisions, antibiotic use could be decreased by over 50%,” Dr. Barbieri said. Before prescribing antibiotic prophylaxis, dermatologists should consider which patients benefit most from it, he added.

The investigators also examined the duration of antibiotic courses. The median course duration of postoperative antibiotics was 7 days. Randomized, controlled trials that collectively included more than 600 patients have failed to demonstrate a benefit of long postoperative courses of antibiotics, compared with perioperative antibiotics alone, said Dr. Barbieri. “While it may be hard to have true perioperative antibiotics available in a dermatology surgical clinic, there likely are opportunities to reduce these postoperative courses to a day or 3 days from this mean of 7 days that we observed in the study.” Reducing these courses would decrease the risk of antibiotic-associated complications such as nausea, diarrhea, and skin rashes, he added.

[email protected]

SOURCE: AAD 2019, Abstract 11356.

WASHINGTON – The prescription of oral antibiotics after benign excisions, malignant excisions, and Mohs surgery has increased over the past decade, according to an analysis presented at the annual meeting of the American Academy of Dermatology.

John Barbieri, MD, a dermatologist and postdoctoral research fellow at the University of Pennsylvania, Philadelphia, who presented the results, and colleagues examined data about antibiotic use in dermatology between 2008 and 2016. Overall, antibiotic use decreased during this period, primarily for chronic conditions such as acne and rosacea. On the other hand, antibiotic use associated with surgical visits increased by approximately 70%.

Using data from 2008 to 2016 in the Optum Clinformatics DataMart deidentified commercial claims database, the researchers performed a repeated cross-sectional analysis of oral antibiotic prescriptions associated with encounters for surgical procedures performed by dermatologists. They found that oral antibiotic prescriptions increased from 2.9% to 4.4% of visits for benign excisions, from 4.2% to 6.3% of visits for malignant excisions, and from 9.9% to 13.8% of visits for Mohs procedures during this time period. Oral antibiotic prescribing was more common for procedures that entailed a flap or graft and among patients with diabetes, female patients, and younger patients.


The investigators observed greater than twofold variation in antibiotic-prescribing rates across geographic census divisions. “If higher-prescribing divisions were to develop antibiotic prescribing rates similar to [those of] lower-prescribing divisions, antibiotic use could be decreased by over 50%,” Dr. Barbieri said. Before prescribing antibiotic prophylaxis, dermatologists should consider which patients benefit most from it, he added.

The investigators also examined the duration of antibiotic courses. The median course duration of postoperative antibiotics was 7 days. Randomized, controlled trials that collectively included more than 600 patients have failed to demonstrate a benefit of long postoperative courses of antibiotics, compared with perioperative antibiotics alone, said Dr. Barbieri. “While it may be hard to have true perioperative antibiotics available in a dermatology surgical clinic, there likely are opportunities to reduce these postoperative courses to a day or 3 days from this mean of 7 days that we observed in the study.” Reducing these courses would decrease the risk of antibiotic-associated complications such as nausea, diarrhea, and skin rashes, he added.

[email protected]

SOURCE: AAD 2019, Abstract 11356.

WASHINGTON – The prescription of oral antibiotics after benign excisions, malignant excisions, and Mohs surgery has increased over the past decade, according to an analysis presented at the annual meeting of the American Academy of Dermatology.

John Barbieri, MD, a dermatologist and postdoctoral research fellow at the University of Pennsylvania, Philadelphia, who presented the results, and colleagues examined data about antibiotic use in dermatology between 2008 and 2016. Overall, antibiotic use decreased during this period, primarily for chronic conditions such as acne and rosacea. On the other hand, antibiotic use associated with surgical visits increased by approximately 70%.

Using data from 2008 to 2016 in the Optum Clinformatics DataMart deidentified commercial claims database, the researchers performed a repeated cross-sectional analysis of oral antibiotic prescriptions associated with encounters for surgical procedures performed by dermatologists. They found that oral antibiotic prescriptions increased from 2.9% to 4.4% of visits for benign excisions, from 4.2% to 6.3% of visits for malignant excisions, and from 9.9% to 13.8% of visits for Mohs procedures during this time period. Oral antibiotic prescribing was more common for procedures that entailed a flap or graft and among patients with diabetes, female patients, and younger patients.


The investigators observed greater than twofold variation in antibiotic-prescribing rates across geographic census divisions. “If higher-prescribing divisions were to develop antibiotic prescribing rates similar to [those of] lower-prescribing divisions, antibiotic use could be decreased by over 50%,” Dr. Barbieri said. Before prescribing antibiotic prophylaxis, dermatologists should consider which patients benefit most from it, he added.

The investigators also examined the duration of antibiotic courses. The median course duration of postoperative antibiotics was 7 days. Randomized, controlled trials that collectively included more than 600 patients have failed to demonstrate a benefit of long postoperative courses of antibiotics, compared with perioperative antibiotics alone, said Dr. Barbieri. “While it may be hard to have true perioperative antibiotics available in a dermatology surgical clinic, there likely are opportunities to reduce these postoperative courses to a day or 3 days from this mean of 7 days that we observed in the study.” Reducing these courses would decrease the risk of antibiotic-associated complications such as nausea, diarrhea, and skin rashes, he added.

[email protected]

SOURCE: AAD 2019, Abstract 11356.

Transcranial magnetic stimulation (TMS) appears to improve recollection memory in cognitively normal older adults, according to a small pilot study published online ahead of print April 17 in Neurology. Stimulation also increased functional MRI signals associated with recollection throughout the hippocampal-cortical network.

“Disruption and abnormal functioning of the hippocampal-cortical network, the region of the brain involved in memory formation, has been linked to age-related memory decline, so it’s exciting to see that, by targeting this region, magnetic stimulation may help improve memory in older adults,” said Joel L. Voss, PhD, of Northwestern University in Chicago. “These results may help us better understand how this network supports memory.”

Recollection is the type of memory most impaired during normal aging. Other types of memory, such as recognition, are relatively spared. Research indicates that multiple sessions of TMS improve recollection and hippocampal-cortical network function in young adults.

Dr. Voss and colleagues performed a pilot study to evaluate whether TMS could improve recollection in older adults. They enrolled 15 cognitively normal older adults (mean age, 72.46 years) into a sham-controlled, single-blind, counterbalanced experiment. Eleven subjects were women. Participants underwent fMRI while learning objects paired with scenes and locations. Investigators administered TMS to lateral parietal locations that were based on each participant’s fMRI connectivity with the hippocampus. Using a within-subjects crossover design, Dr. Voss’s group assessed participants’ recollection and recognition memory at baseline and 24 hours and also 1 week after five consecutive daily sessions of full-intensity stimulation, compared with low-intensity sham stimulation.

At baseline, participants had impaired recollection, but not impaired recognition, compared with a historical sample of younger adults. At 24 hours, TMS provided robust recollection improvement and weak recognition improvement, compared with sham. TMS improved recollection by 31.1% from baseline, and sham yielded a nonsignificant change of −3.1%. Recollection improvements after TMS were consistent across participants. Recognition changed by a nonsignificant 2.8% following TMS and by a nonsignificant −2.9% following sham.

The investigators also found a significant and consistent increase in fMRI recollection activity for the targeted hippocampal-cortical network, but not for the control frontal-parietal network. They observed no increased fMRI activity for recognition.

“These findings demonstrate a causal link between recollection and the hippocampal-cortical network in older adults,” said Dr. Voss. “While our small study examined age-related memory loss, it did not examine this stimulation in people with memory loss from more serious conditions such as mild cognitive impairment or Alzheimer’s disease.” Furthermore, the study was designed to test for neural and behavioral target engagement, but not clinical efficacy, he added.

The study’s limitations included its small sample size, its single-site design, and its lack of active control stimulation. Nevertheless, it identified specific and consistent effects of stimulation across participants that were consistent with previous findings in younger adults. “These findings motivate future studies to optimize the effectiveness of noninvasive stimulation for treatment of age-related memory impairment and to improve mechanistic understanding of the hippocampal-cortical networks that support episodic memory across the lifespan,” said Dr. Voss.

The National Institute on Aging, as well as the Northwestern University Cognitive Neurology and Alzheimer’s Disease Center, supported the study.

[email protected]

SOURCE: Nilakantan AS et al. Neurology. 2019 Apr 17 doi: 10.1212/WNL.0000000000007502.

Transcranial magnetic stimulation (TMS) appears to improve recollection memory in cognitively normal older adults, according to a small pilot study published online ahead of print April 17 in Neurology. Stimulation also increased functional MRI signals associated with recollection throughout the hippocampal-cortical network.

“Disruption and abnormal functioning of the hippocampal-cortical network, the region of the brain involved in memory formation, has been linked to age-related memory decline, so it’s exciting to see that, by targeting this region, magnetic stimulation may help improve memory in older adults,” said Joel L. Voss, PhD, of Northwestern University in Chicago. “These results may help us better understand how this network supports memory.”

Recollection is the type of memory most impaired during normal aging. Other types of memory, such as recognition, are relatively spared. Research indicates that multiple sessions of TMS improve recollection and hippocampal-cortical network function in young adults.

Dr. Voss and colleagues performed a pilot study to evaluate whether TMS could improve recollection in older adults. They enrolled 15 cognitively normal older adults (mean age, 72.46 years) into a sham-controlled, single-blind, counterbalanced experiment. Eleven subjects were women. Participants underwent fMRI while learning objects paired with scenes and locations. Investigators administered TMS to lateral parietal locations that were based on each participant’s fMRI connectivity with the hippocampus. Using a within-subjects crossover design, Dr. Voss’s group assessed participants’ recollection and recognition memory at baseline and 24 hours and also 1 week after five consecutive daily sessions of full-intensity stimulation, compared with low-intensity sham stimulation.

At baseline, participants had impaired recollection, but not impaired recognition, compared with a historical sample of younger adults. At 24 hours, TMS provided robust recollection improvement and weak recognition improvement, compared with sham. TMS improved recollection by 31.1% from baseline, and sham yielded a nonsignificant change of −3.1%. Recollection improvements after TMS were consistent across participants. Recognition changed by a nonsignificant 2.8% following TMS and by a nonsignificant −2.9% following sham.

The investigators also found a significant and consistent increase in fMRI recollection activity for the targeted hippocampal-cortical network, but not for the control frontal-parietal network. They observed no increased fMRI activity for recognition.

“These findings demonstrate a causal link between recollection and the hippocampal-cortical network in older adults,” said Dr. Voss. “While our small study examined age-related memory loss, it did not examine this stimulation in people with memory loss from more serious conditions such as mild cognitive impairment or Alzheimer’s disease.” Furthermore, the study was designed to test for neural and behavioral target engagement, but not clinical efficacy, he added.

The study’s limitations included its small sample size, its single-site design, and its lack of active control stimulation. Nevertheless, it identified specific and consistent effects of stimulation across participants that were consistent with previous findings in younger adults. “These findings motivate future studies to optimize the effectiveness of noninvasive stimulation for treatment of age-related memory impairment and to improve mechanistic understanding of the hippocampal-cortical networks that support episodic memory across the lifespan,” said Dr. Voss.

The National Institute on Aging, as well as the Northwestern University Cognitive Neurology and Alzheimer’s Disease Center, supported the study.

[email protected]

SOURCE: Nilakantan AS et al. Neurology. 2019 Apr 17 doi: 10.1212/WNL.0000000000007502.

Transcranial magnetic stimulation (TMS) appears to improve recollection memory in cognitively normal older adults, according to a small pilot study published online ahead of print April 17 in Neurology. Stimulation also increased functional MRI signals associated with recollection throughout the hippocampal-cortical network.

“Disruption and abnormal functioning of the hippocampal-cortical network, the region of the brain involved in memory formation, has been linked to age-related memory decline, so it’s exciting to see that, by targeting this region, magnetic stimulation may help improve memory in older adults,” said Joel L. Voss, PhD, of Northwestern University in Chicago. “These results may help us better understand how this network supports memory.”

Recollection is the type of memory most impaired during normal aging. Other types of memory, such as recognition, are relatively spared. Research indicates that multiple sessions of TMS improve recollection and hippocampal-cortical network function in young adults.

Dr. Voss and colleagues performed a pilot study to evaluate whether TMS could improve recollection in older adults. They enrolled 15 cognitively normal older adults (mean age, 72.46 years) into a sham-controlled, single-blind, counterbalanced experiment. Eleven subjects were women. Participants underwent fMRI while learning objects paired with scenes and locations. Investigators administered TMS to lateral parietal locations that were based on each participant’s fMRI connectivity with the hippocampus. Using a within-subjects crossover design, Dr. Voss’s group assessed participants’ recollection and recognition memory at baseline and 24 hours and also 1 week after five consecutive daily sessions of full-intensity stimulation, compared with low-intensity sham stimulation.

At baseline, participants had impaired recollection, but not impaired recognition, compared with a historical sample of younger adults. At 24 hours, TMS provided robust recollection improvement and weak recognition improvement, compared with sham. TMS improved recollection by 31.1% from baseline, and sham yielded a nonsignificant change of −3.1%. Recollection improvements after TMS were consistent across participants. Recognition changed by a nonsignificant 2.8% following TMS and by a nonsignificant −2.9% following sham.

The investigators also found a significant and consistent increase in fMRI recollection activity for the targeted hippocampal-cortical network, but not for the control frontal-parietal network. They observed no increased fMRI activity for recognition.

“These findings demonstrate a causal link between recollection and the hippocampal-cortical network in older adults,” said Dr. Voss. “While our small study examined age-related memory loss, it did not examine this stimulation in people with memory loss from more serious conditions such as mild cognitive impairment or Alzheimer’s disease.” Furthermore, the study was designed to test for neural and behavioral target engagement, but not clinical efficacy, he added.

The study’s limitations included its small sample size, its single-site design, and its lack of active control stimulation. Nevertheless, it identified specific and consistent effects of stimulation across participants that were consistent with previous findings in younger adults. “These findings motivate future studies to optimize the effectiveness of noninvasive stimulation for treatment of age-related memory impairment and to improve mechanistic understanding of the hippocampal-cortical networks that support episodic memory across the lifespan,” said Dr. Voss.

The National Institute on Aging, as well as the Northwestern University Cognitive Neurology and Alzheimer’s Disease Center, supported the study.

[email protected]

SOURCE: Nilakantan AS et al. Neurology. 2019 Apr 17 doi: 10.1212/WNL.0000000000007502.