Categories
Multiple sclerosis

Does breastfeeding influence the risk of postpartum MS relapses?

Association between breastfeeding and postpartum multiple sclerosis relapses: a systematic review and meta-analysis.

Krysko KM, Rutatangwa A, Graves J, Lazar A, Waubant E.

JAMA Neurol 2019 (Epub ahead of print).

Abstract

BACKGROUND:

Multiple sclerosis (MS) relapses may be increased in the postpartum period, and whether breastfeeding is associated with reduction in the risk of postpartum relapses remains controversial.

METHODS

PubMed and Embase were searched for studies assessing the association between breastfeeding and MS disease activity published between January 1, 1980, and July 11, 2018, as well as reference lists of selected articles.

RESULTS:

The search identified 462 unique citations, and 24 (2974 women) satisfied eligibility criteria and were included, of which 16 were included in the quantitative meta-analysis. The pooled summary odds ratio for the association of breastfeeding with postpartum relapses was 0.63 (95% CI, 0.45-0.88; P = .006) compared with a reference of nonbreastfeeding. Pooled adjusted hazard ratio across 4 studies that reported this finding was 0.57 (95% CI, 0.38-0.85; P = .006). There was moderate heterogeneity (I2 = 48%), which was explained by variable prepregnancy relapse rate, postpartum follow-up duration, and the publication year. A stronger association was seen in studies of exclusive rather than nonexclusive breastfeeding, although both demonstrated an association. Studies were rated at moderate and serious risk of bias, with concern for residual confounding, although sensitivity analysis including only moderate quality studies was consistent with a protective outcome of breastfeeding.

CONCLUSIONS:

These findings suggest that breastfeeding is protective against postpartum relapses in multiple sclerosis, although high-quality prospective studies to date are limited and well-designed observational studies that aim to emulate a randomized trial would be of benefit.

This paper is cited in the neurochecklist:

Multiple sclerosis (MS): poor prognostic factors

Mothers from Eastern Ukraine attend Training on Breastfeeding. UNICEF Ukraine on Flickr. https://www.flickr.com/photos/unicefua/17063692941

Abstract link

Categories
Vascular

Is dabigatran as effective as warfarin for cerebral vein thrombosis?

RE-SPECT CVT Study Group. Safety and efficacy of dabigatran etexilate vs dose-adjusted warfarin in patients with cerebral venous thrombosis: a randomized clinical trial.

Ferro JM, Coutinho JM, Dentali F, et al;

JAMA Neurol 2019 (Epub ahead of print).

Abstract

BACKGROUND:

Patients with cerebral venous thrombosis (CVT) are at risk of recurrent venous thrombotic events (VTEs). Non-vitamin K oral anticoagulants have not been evaluated in randomized controlled trials in CVT.

METHODS:

RE-SPECT CVT is an exploratory, prospective, randomized (1:1), parallel-group, open-label, multicenter clinical trial with blinded end-point adjudication (PROBE design). It was performed from December 21, 2016, to June 22, 2018, with a follow-up of 25 weeks, at 51 tertiary sites in 9 countries (France, Germany, India, Italy, the Netherlands, Poland, Portugal, Russia, and Spain). Adult consecutive patients with acute CVT, who were stable after 5 to 15 days of treatment with parenteral heparin, were screened for eligibility. Patients with CVT associated with central nervous system infection or major trauma were excluded, but those with intracranial hemorrhage from index CVT were allowed to participate. After exclusions, 120 patients were randomized. Data were analyzed following the intention-to-treat approach.

INTERVENTIONS:

Dabigatran, 150 mg twice daily, or dose-adjusted warfarin for a treatment period of 24 weeks.

RESULTS:

In total, 120 patients with CVT were randomized to the 2 treatment groups (60 to dabigatran and 60 to dose-adjusted warfarin). Of the randomized patients, the mean (SD) age was 45.2 (13.8) years, and 66 (55.0%) were women. The mean (SD) duration of exposure was 22.3 (6.16) weeks for the dabigatran group and 23.0 (5.20) weeks for the warfarin group. No recurrent VTEs were observed. One (1.7%; 95% CI, 0.0-8.9) major bleeding event (intestinal) was recorded in the dabigatran group, and 2 (3.3%; 95% CI, 0.4-11.5) (intracranial) in the warfarin group. One additional patient (1.7; 95% CI, 0.0-8.9) in the warfarin group experienced a clinically relevant non-major bleeding event. Recanalization occurred in 33 patients in the dabigatran group (60.0%; 95% CI, 45.9-73.0) and in 35 patients in the warfarin group (67.3%; 95% CI, 52.9-79.7).

CONCLUSIONS:

This trial found that patients who had cerebral vein thrombosis anticoagulated with either dabigatran or warfarin had low risk of recurrent venous thromboembolic events, and the risk of bleeding was similar with both medications, suggesting that both dabigatran and warfarin may be safe and effective for preventing recurrent VTEs in patients with CVT.

This paper is cited in the neurochecklist:

Cerebral vein thrombosis (CVT): anticoagulant treatment

By MarinaVladivostokOwn work, CC0, Link

Abstract link

 

Categories
Multiple sclerosis

How long can the pre-symptomatic phase of MS last?

Serum neurofilament light chain levels in patients with presymptomatic multiple sclerosis.

Bjornevik K, Munger KL, Cortese M, et al.

JAMA Neurol 2019 (Epub ahead of print).

Abstract

BACKGROUND:

Unrecognized demyelinating events often precede the clinical onset of multiple sclerosis (MS). Identification of these events at the time of occurrence would have implications for early diagnosis and the search of causal factors for the disease.

OBJECTIVE:

To assess whether serum neurofilament light chain (sNfL) levels are elevated before the clinical MS onset.

METHODS:

Nested case-control study among US military personnel who have serum samples stored in the US Department of Defense Serum Repository. Serum samples were collected from 2000 to 2011; sNfL assays and data analyses were performed from 2018 to 2019. We selected 60 case patients with MS who either had 2 samples collected before onset (mean follow-up, 6.3 years) or 1 sample collected before and 1 after onset (mean follow-up, 1.3 years), among 245 previously identified case patients. For each case, we randomly selected 1 of 2 previously identified control individuals matched by age, sex, race/ethnicity, and dates of sample collection. The sample size was chosen based on the available funding.

RESULTS:

Mean age at baseline was 27.5 years, and 92 of 120 participants (76.7%) were men. Serum NfL levels were higher in case patients with MS compared with their matched control individuals in samples drawn a median of 6 years (range, 4-10 years) before the clinical onset (median, 16.7 pg/mL; interquartile range [IQR], 12.6-23.1 pg/mL vs 15.2 pg/m; IQR, 10.3-19.9 pg/mL; P = .04). This difference increased with decreasing time to the case clinical onset (estimated coefficient for interaction with time = 0.063; P = .008). A within-person increase in presymptomatic sNfL levels was associated with higher MS risk (rate ratio for ≥5 pg/mL increase, 7.50; 95% CI, 1.72-32.80). The clinical onset was associated with a marked increase in sNfL levels (median, 25.0; IQR, 17.1-41.3 vs 45.1; IQR, 27.0-102.7 pg/mL for presymptomatic and postonset MS samples; P = .009).

CONCLUSIONS:

The levels of sNfL were increased 6 years before the clinical MS onset, indicating that MS may have a prodromal phase lasting several years and that neuroaxonal damage occurs already during this phase.

This paper is cited in the neurochecklist:

Multiple sclerosis (MS): non-modifiable risk factors

By GerryShaw – Standard tissue culture and immunofluorescencePreviously published: Unpublished, CC BY-SA 3.0, Link

Abstract link

Categories
Multiple sclerosis

Does obesity impair treatment response in multiple sclerosis?

Association of obesity with multiple sclerosis risk and response to first-line disease modifying drugs in children

Huppke B, Ellenberger D, Hummel H, et al.

JAMA Neurol 2019 (Epub ahead of print).

Abstract

BACKGROUND:

Obesity reportedly increases the risk of pediatric multiple sclerosis (MS), but little is known about its association with disease course.

OBJECTIVE:

To investigate the association of obesity with pediatric MS risk and with first-line therapy response among children with MS.

METHODS:

This single-center retrospective study used the medical records and database at the Center for MS in Childhood and Adolescence, Göttingen, Germany. The study included 453 patients with relapsing-remitting pediatric MS and body mass index (BMI) measurement taken within 6 months of diagnosis. Onset of the disease occurred between April 28, 1990, and June 26, 2016, and the mean disease duration was 38.4 months. Data were collected from July 14, 2016, to December 18, 2017. Data on BMIs were stratified by sex and age using German BMI references and compared with the BMI data of 14 747 controls from a nationwide child health survey for odds ratio (OR) estimates. Baseline magnetic resonance imaging findings, intervals between first and second MS attacks, annualized relapse rates before and during treatment with interferon beta-1a or -1b and glatiramer acetate, frequency of second-line treatment, and Expanded Disability Status Scale (EDSS) scores were compared between nonoverweight (BMI≤90th percentile), overweight (BMI>90th-97th percentile), and obese (BMI>97th percentile) patients.

RESULTS:

In total, 453 patients with pediatric MS were included, of whom 306 (67.5%) were female, and the mean (SD) age at diagnosis was 13.7 (2.7) years. At diagnosis, 126 patients (27.8%) were overweight or obese, with obesity associated with statistically significant twofold odds of MS in both sexes (girls OR, 2.19; 95% CI, 1.5-3.1; P < .001 vs boys OR, 2.14; 95% CI, 1.3-3.5; P = .003). Obese patients, compared with nonoverweight patients, had statistically significantly more relapses on first-line treatment with interferon beta and glatiramer acetate (ARR, 1.29 vs 0.72; P < .001) and a higher rate of second-line treatment (21 [56.8%] of 37 vs 48 [38.7%] of 124; P = .06). Baseline neuroimaging, interval between first and second MS attacks, pretreatment relapses, and EDSS progression scores were not correlated with BMI.

CONCLUSIONS:

In this study, increased pediatric MS risk appeared to be associated with obesity, and obese patients did not respond well to first-line medications; altered pharmacokinetics appeared to be most likely factors in treatment response, suggesting that achieving healthy weight or adjusting the dose according to BMI could improve therapy response.

This paper is cited in the neurochecklist:

Multiple sclerosis (MS): poor prognostic factors

Abstract link

Standing on a Scale. Foodfacts pm on Flickr. https://www.flickr.com/photos/134352277@N06/18936767418
Categories
Stroke

How much does clopidogrel increase the bleeding risk of aspirin?

Risk for major hemorrhages in patients receiving clopidogrel and aspirin compared with aspirin alone after transient ischemic attack or minor ischemic stroke: a secondary analysis of the POINT randomized clinical trial.

Tillman H, Johnston SC, Farrant M, et al.

JAMA Neurol 2019; 76:774-782.

Abstract

IMPORTANCE:

Results show the short-term risk of hemorrhage in treating patients with acute transient ischemic attack (TIA) or minor acute ischemic stroke (AIS) with clopidogrel plus aspirin or aspirin alone.

OBJECTIVE:

To characterize the frequency and kinds of major hemorrhages in the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial.

METHODS:

This secondary analysis of the POINT randomized, double-blind clinical trial conducted in 10 countries in North America, Europe, and Australasia included patients with high-risk TIA or minor AIS who were randomized within 12 hours of symptom onset and followed up for 90 days. The total enrollment, which occurred from May 28, 2010, through December 17, 2017, was 4881 and constituted the intention-to-treat group; 4819 (98.7%) were included in the as-treated analysis group. The primary safety analyses were as-treated, classifying patients based on study drug actually received. Intention-to-treat analyses were performed as secondary analyses. Data were analyzed in April 2018.

INTERVENTIONS:

Patients were assigned to receive clopidogrel (600 mg loading dose on day 1 followed by 75 mg daily for days 2-90) or placebo; all patients also received open-label aspirin, 50 to 325 mg/d.

MAIN OUTCOMES AND MEASURES:

The primary safety outcome was all major hemorrhages. Other safety outcomes included minor hemorrhages.

RESULTS:

A total of 269 sites worldwide randomized 4881 patients (median age, 65.0 years [interquartile range, 55-74 years]; 2195 women [45.0%]); the primary results have been published previously. In the as-treated analyses, major hemorrhage occurred in 21 patients (0.9%) receiving clopidogrel  plus aspirin and 6 (0.2%) in the aspirin alone group (hazard ratio, 3.57; 95% CI, 1.44-8.85; P = .003; number needed to harm, 159). There were 4 fatal hemorrhages (0.1%; 3 in the clopidogrel plus aspirin group and 1 in the aspirin alone group); 3 of the 4 were intracranial. There were 7 intracranial hemorrhages (0.1%); 5 were in the clopidogrel plus aspirin group and 2 in the aspirin plus placebo group. The most common location of major hemorrhages was in the gastrointestinal tract.

CONCLUSIONS:

The risk for major hemorrhages in patients receiving either clopidogrel plus aspirin or aspirin alone after TIA or minor AIS was low. Nevertheless, treatment with clopidogrel plus aspirin increased the risk of major hemorrhages  over aspirin alone from 0.2% to 0.9%.

This paper is cited in the neurochecklist:

Secondary stroke prevention: antiplatelets

Abstract link

By MarinaVladivostokOwn work, CC0, Link
Categories
Headaches

Does IIH increase the risk of cerebrovascular events?

Association between idiopathic intracranial hypertension and risk of cardiovascular diseases in women in the United Kingdom.

Adderley NJ, Subramanian A, Nirantharakumar K, et al.

JAMA Neurol 2019 (Epub ahead of print).

Abstract

BACKGROUND:

Cardiovascular disease (CVD) risk has not been previously evaluated in a large matched cohort study in idiopathic intracranial hypertension (IIH).

OBJECTIVES:

To estimate the risk of composite cardiovascular events, heart failure, ischemic heart disease, stroke/transient ischemic attack (TIA), type 2 diabetes, and hypertension in women with idiopathic intracranial hypertension and compare it with the risk in women, matched on body mass index (BMI) and age, without the condition; and to evaluate the prevalence and incidence of IIH.

METHODS:

This population-based matched controlled cohort study used 28 years of data, from January 1, 1990, to January 17, 2018, from The Health Improvement Network (THIN), an anonymized, nationally representative electronic medical records database in the United Kingdom. All female patients aged 16 years or older were eligible for inclusion. Female patients with IIH (n = 2760) were included and randomly matched with up to 10 control patients (n = 27 125) by BMI and age.

RESULTS:

In total, 2760 women with IIH and 27 125 women without IIH were included. Age and BMI were similar between the 2 groups, with a median (interquartile range) age of 32.1 (25.6-42.0) years in the exposed group and 32.1 (25.7-42.1) years in the control group; in the exposed group 1728 women (62.6%) were obese, and in the control group 16514 women (60.9%) were obese. Higher absolute risks for all cardiovascular outcomes were observed in women with IIH compared with control patients. The aHRs were as follows: composite cardiovascular events, 2.10 (95% CI, 1.61-2.74; P < .001); heart failure, 1.97 (95% CI, 1.16-3.37; P = .01); ischemic heart disease, 1.94 (95% CI, 1.27-2.94; P = .002); stroke/TIA, 2.27 (95% CI, 1.61-3.21; P < .001); type 2 diabetes, 1.30 (95% CI, 1.07-1.57; P = .009); and hypertension, 1.55 (95% CI, 1.30-1.84; P < .001). The incidence of IIH in female patients more than tripled between 2005 and 2017, from 2.5 to 9.3 per 100 000 person-years. Similarly, IIH prevalence increased in the same period, from 26 to 79 per 100 000 women. Incidence increased markedly with BMI higher than 30.

CONCLUSIONS:

Idiopathic intracranial hypertension in women appeared to be associated with a 2-fold increase in cerebrovascular disease risk; change in patient care to modify risk factors for CVD may reduce long-term morbidity for women with IIH and warrants further evaluation.

This paper is cited in the neurochecklist:

Idiopathic intracranial hypertension (IIH): typical clinical features 

Abstract link

Internet Archive Book Images on Flickr. https://www.flickr.com/photos/internetarchivebookimages/14586373420/
Categories
Parkinson's disease

Is bipolar disorder a risk factor for Parkinson’s disease?

Risk of developing Parkinson disease in bipolar disorder: a systematic review and meta-analysis

Faustino PR, Duarte GS, Chendo I, et al

JAMA Neurol 2019 (Epub ahead of print)

Abstract

BACKGROUND:

Parkinson disease (PD) manifests by motor and non-motor symptoms, which may be preceded by mood disorders by more than a decade. Bipolar disorder (BD) is characterized by cyclic episodes of depression and mania. It is also suggested that dopamine might be relevant in the pathophysiology of BD.

METHODS:

To assess the association of BD with a later diagnosis of idiopathic PD. An electronic literature search was performed of Cochrane Controlled Register of Trials, MEDLINE, Embase, and PsycINFO from database inception to May 2019 using the terms Parkinson disease, bipolar disorder, and mania, with no constraints applied. Studies that reported data on the likelihood of developing PD in BD vs non-BD populations were included. Two review authors independently conducted the study selection. Two review authors independently extracted study data. Data were pooled using a random-effects model, results were abstracted as odds ratios and 95% CIs, and heterogeneity was reported as I2.

RESULTS:

Seven studies were eligible for inclusion and included 4 374 211 participants overall. A previous diagnosis of BD increased the likelihood of a subsequent diagnosis of idiopathic PD (odds ratio, 3.35; 95% CI, 2.00-5.60; I2 = 92%). A sensitivity analysis was performed by removing the studies that had a high risk of bias and also showed an increased risk of PD in people with BD (odds ratio, 3.21; 95% CI, 1.89-5.45; I2 = 94%). Preplanned subgroup analyses according to study design and diagnostic certainty failed to show a significant effect.

CONCLUSIONS:

This review suggests that patients with BD have a significantly increased risk of developing PD compared with the general population. Subgroup analyses suggested a possible overestimation in the magnitude of the associations. These findings highlight the probability that BD may be associated with a later development of PD and the importance of the differential diagnosis of parkinsonism features in people with BD.

This paper is cited in the neurochecklist:

Parkinson’s disease (PD): risk factors

Abstract link

By National Institute of Mental Health (NIMH), National Institute of Health (NIH), U.S. Department of Health and Human Services. – https://www.nimh.nih.gov/health/publications/bipolar-disorder/index.shtml#pub1, Public Domain, Link
Categories
Headaches

Does migraine reduce the risk of diabetes?

Associations between migraine and type 2 diabetes in women: findings from the E3N Cohort Study

Fagherazzi G, El Fatouhi D, Fournier A, et al.

JAMA Neurol 2019; 76:257-263.

Abstract

BACKGROUND:

Little is known about the associations between migraine and type 2 diabetes and the temporality of the association between these 2 diseases. To evaluate the association between migraine and type 2 diabetes incidence as well as the evolution of the prevalence of active migraine before and after type 2 diabetes diagnosis.

METHODS:

We used data from the E3N cohort study, a French prospective population-based study initiated in 1990 on a cohort of women born between 1925 and 1950. The E3N study participants are insured by a health insurance plan that mostly covers teachers. From the eligible women in the E3N study, we included those who completed the 2002 follow-up questionnaire with information available on migraine. We then excluded prevalent cases of type 2 diabetes, leaving a final sample of women who were followed up between 2004 and 2014. All potential occurrences of type 2 diabetes were identified through a drug reimbursement database. Statistical analyses were performed in March 2018.

RESULTS:

From the 98 995 women in the study, 76 403 women completed the 2002 follow-up survey. Of these, 2156 were excluded because they had type 2 diabetes, leaving 74 247 women. Participants had a mean (SD) age of 61 (6) years at baseline, and all were free of type 2 diabetes. During 10 years of follow-up, 2372 incident type 2 diabetes cases occurred. A lower risk of type 2 diabetes was observed for women with active migraine compared with women with no migraine history (univariate hazard ratio, 0.80 [95% CI, 0.67-0.96], multivariable-adjusted hazard ratio, 0.70 [95% CI, 0.58-0.85]). We also observed a linear decrease in active migraine prevalence from 22% (95% CI, 16%-27%) to 11% (95% CI, 10%-12%) during the 24 years prior to diabetes diagnosis, after adjustment for potential type 2 diabetes risk factors. A plateau of migraine prevalence around 11% was then observed for 22 years after diagnosis.

CONCLUSIONS:

We observed a lower risk of developing type 2 diabetes for women with active migraine and a decrease in active migraine prevalence prior to diabetes diagnosis. Further targeted research should focus on understanding the mechanisms involved in explaining these findings.

This paper is cited in the neurochecklist:

Migraine: risk factors

Abstract link

By Reversing Your Diabetes Today – http://reversingyourdiabetestoday.com/https://pixabay.com/en/diabetes-blood-finger-glucose-777001/, CC0, Link
Categories
Multiple sclerosis

Do steroids have to be administered intravenously for acute optic neuritis?

Effect of treating acute optic neuritis with bioequivalent oral vs intravenous corticosteroids: a randomized clinical trial.

Morrow SA, Fraser JA, Day C, et al.

JAMA Neurol 2018; 75:690-696.

Abstract

IMPORTANCE:

Intravenous (IV) administration of corticosteroids is the standard of care in the treatment of acute optic neuritis. However, it is uncertain whether a bioequivalent dose of corticosteroid administered orally, which may be more cost-efficient and convenient for patients, is as effective as IV administration in the treatment of acute optic neuritis.

OBJECTIVE:

To determine whether recovery of vision following treatment of acute optic neuritis with a high-dose IV corticosteroid is superior to that with a bioequivalent dose of an oral corticosteroid.

DESIGN, SETTING, AND PARTICIPANTS:

This single-blind (participants unblinded) randomized clinical trial with 6-month follow-up was conducted at a single tertiary care center in London, Ontario, Canada. Participants were enrolled from March 2012 to May 2015, with the last participant’s final visit occurring November 2015. Patients 18 to 64 years of age presenting within 14 days of acute optic neuritis onset, without any recovery at time of randomization and without history of optic neuritis in the same eye, were screened. Inclusion criteria included best-corrected visual acuity (BCVA) of 20/40 or worse and corticosteroids deemed required by treating physician. In total, 89 participants were screened; 64 were eligible, but 9 declined to participate. Thus, 55 participants were enrolled and randomized. Primary analysis was unadjusted and according to the intention-to-treat principle.

INTERVENTIONS:

Participants were randomized 1:1 to the IV methylprednisolone sodium succinate (1000-mg) or oral prednisone (1250-mg) group.

MAIN OUTCOMES AND MEASURES:

Primary outcome was recovery of the latency of the P100 component of the visual evoked potential at 6 months. Secondary outcomes were the P100 latency at 1 month and BCVA as assessed with Early Treatment Diabetic Retinopathy Study letter scores on the alphabet chart and scores on low-contrast letters at 1 and 6 months.

RESULTS:

Of 55 randomized participants, the final analyzed cohort comprised 23 participants in the IV and 22 in the oral treatment groups. The mean (SD) age of the cohort was 34.6 (9.5) years, and there were 28 women (62.2%). At 6 months’ recovery, P100 latency in the IV group improved by 62.9 milliseconds (from a mean [SD] of 181.9 [53.6] to 119.0 [16.5] milliseconds), and the oral group improved by 66.7 milliseconds (from a mean [SD] of 200.5 [67.2] to 133.8 [31.5] milliseconds), with no significant difference between groups (P = .07). Similarly, no significant group difference was found in the mean P100 latency recovery at 1 month. For BCVA, recovery between the groups did not reach statistical significance at 1 month or 6 months. In addition, improvements in low-contrast (1.25% and 2.5%) BCVA were not significantly different between treatment groups at 1 or 6 months’ recovery.

CONCLUSIONS AND RELEVANCE:

This study finds that bioequivalent doses of oral corticosteroids may be used as an alternative to IV corticosteroids to treat acute optic neuritis.

This paper is cited in the neurochecklist:

Multiple sclerosis (MS): treatment of relapses

Abstract link

Optic nerve side view. Francisco Bengoa on Flikr. https://www.flickr.com/photos/frecuenciamedicafb/7404373800