Neurological Disorders: Monthly Essentials November 2017

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The 4 essential studies on Neurological Disorders this month, selected from 1721 peer-reviewed studies

1. Prochlorperazine is superior to hydromorphone for achieving sustained relief of moderate to severe migraine. See our essential synopsis of the article from Neurology below.

2. Eculizumab, a terminal complement inhibitor, did not significantly improve activities of daily living in patients with refractory generalized myasthenia gravis, but some other outcomes were better with the drug. See our essential synopsis of the article from Lancet Neurol below.

3. Among infants with hypoxic-ischemic encephalopathy, hypothermia initiated at 6-24 h after birth nonsignificantly reduced death or disability. See our essential synopsis of the article from JAMA below.

4. Among patients with prodromal Alzheimer’s disease, a multinutrient drink was not superior for slowing cognitive deterioration, but the control group fared better than expected. See our essential synopsis of the article from Lancet Neurol below.


1. For acute migraine, IV prochlorperazine far outperforms IV hydromorphone



Source: Neurology

Takeaway
  • Prochlorperazine is superior to hydromorphone for achieving sustained relief of moderate to severe migraine.
Key results
  • The trial was stopped early, after enrollment of 127 patients, because of clear superiority of prochlorperazine.
  • Rate of sustained headache relief was 60% with prochlorperazine vs 31% with hydromorphone (difference, 28%; 95% CI, 12%-45%).
  • Number needed to treat was just 4 (95% CI, 2-9).
  • Groups did not differ on incidences of restlessness and drowsiness.
  • Among patients improving after medication, rate of relapse was similar.
Study design
  • A randomized double-blind controlled phase 4 trial among adults seeking care for migraine with moderate to severe pain at 2 New York City emergency departments (EDs).
  • Patients received intravenous (IV) hydromorphone (1 mg) plus placebo or IV prochlorperazine (10 mg) plus diphenhydramine (25 mg) to prevent akathisia.
  • Main outcome was sustained headache relief (achieving headache level of mild/none within 2 h and maintaining it for 48 h without rescue medication).
  • Funding: None.
Why this matters
  • Hydromorphone is used in about 25% of ED visits for migraine, but evidence supporting its use is scant.

View Abstract


2. Refractory myasthenia gravis: eculizumab appears down but not out



Source: Lancet Neurol

Takeaway
  • Eculizumab, a terminal complement inhibitor, did not significantly improve activities of daily living in patients with refractory generalized myasthenia gravis, but some other outcomes were better with the drug.
Key results
  • The eculizumab and placebo groups did not differ in change in Myasthenia Gravis-Activities of Daily Living total score (least-squares mean rank, 56.6 vs 68.3; P=.0698).
  • None of the patients developed meningococcal infection or died.
  • Leading adverse events in both groups were headache and upper respiratory tract infection (eculizumab, 16%, placebo, 19%).
  • Patients in the eculizumab group had lower incidences of exacerbation (10% vs 24%), need for rescue therapy (10% vs 19%), and hospitalization (15% vs 29%).
Study design
  • A multicenter, phase 3, randomized controlled trial (REGAIN) among 125 patients from North America, Latin America, Europe, and Asia with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis that was refractory to conventional immunotherapies.
  • Patients were randomly assigned to 26 wk of double-blind treatment with eculizumab or placebo.
  • Main outcome was change in Myasthenia Gravis-Activities of Daily Living total score.
  • Funding: Alexion Pharmaceuticals.
Why this matters
  • Refractory myasthenia gravis causes substantial, sometimes life-threatening morbidity.

View Abstract


3. Neonatal hypoxic-ischemic encephalopathy: cooling beneficial even when delayed



Source: JAMA

Takeaway
  • Among infants with hypoxic-ischemic encephalopathy, hypothermia initiated at 6-24 h after birth nonsignificantly reduced death or disability.
Key results
  • Incidence of the main composite outcome was 24.4% among hypothermic infants and 27.9% among noncooled infants (absolute difference, 3.5%; 95% CI, –1% to 17%).
  • There was a 76% posterior probability of reduced death or disability with hypothermia in a Bayesian analysis.
  • Probability of a reduction of at least 1% in this outcome with hypothermia vs noncooling was 71%.
Study design
  • A multicenter, randomized controlled trial among infants at ≥36 wk gestation with moderate/severe hypoxic-ischemic encephalopathy enrolled at 6-24 h after birth.
  • Infants were randomly assigned to hypothermia (targeted esophageal temperature 33.5°C) for 96 h then rewarming, or no cooling (37.0°C).
  • Main outcome was composite of death or disability (moderate or severe) at 18-22 mo.
  • Funding: National Institutes of Health; National Institute of Child Health and Human Development; National Center for Research Resources; National Center for Advancing Translational Sciences.
Why this matters
  • Hypothermia may be delayed if infants are born in remote areas or nonequipped facilities, or encephalopathy is not promptly recognized.

View Abstract


4. Prodromal Alzheimer’s disease: jury still out on benefit of multinutrient drink



Source: Lancet Neurol

Takeaway
  • Among patients with prodromal Alzheimer’s disease, a multinutrient drink was not superior for slowing cognitive deterioration, but the control group fared better than expected.
Key results
  • Multinutrient and control groups did not differ on mean change in neuropsychological test battery score (mean standard deviation [SD], −0.028 vs −0.108; P=.166).
  • However, decline in the control group was smaller than expected (mean SD, −0.4).
  • Overall, 21% of participants withdrew.
  • The groups did not differ on rate of serious adverse events (22% vs 19%; P=.487), none of which were deemed intervention related.
Study design
  • A randomized double-blind controlled trial among 382 individuals with prodromal Alzheimer’s disease in Finland, Germany, Netherlands, and Sweden.
  • Participants consumed 125 mL once daily of a multinutrient drink (Souvenaid) or a placebo control drink.
  • Souvenaid contains Fortasyn Connect (docosahexaenoic acid; eicosapentaenoic acid; uridine monophosphate; choline; vitamins B12, B6, C, E, and folic acid; phospholipids; selenium).
  • Main outcome was 24-mo change in composite score of cognitive performance based on a neuropsychological test battery.
  • Funding: European Commission 7th Framework Programme.
Why this matters
  • Prevention trials have shown promise of nonpharmacologic approaches, including dietary interventions.

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