Is there an association between previous migraine and cryptogenic TIA or ischemic stroke in older patients?

Presenter: Sammy Ming Hin Lee, MD, PhD

Link to Presentation: Journal Club 28 June 2016

Clinical Question: 

Is there an association between previous migraine and cryptogenic TIA or ischemic stroke in older patients?

Journal Club Article: 

Li, L. et al.  Age-specific association of migraine with cryptogenic TIA and stroke: Population-based study.  Neurology, 2015 Oct 27;85(17):1444-51.  PDF here: Li, et al

 

Methodology:

Consecutive cases with a first TIA or ischemic stroke in the first 10 years (April 1, 2002, to March 31, 2012) of the Oxford Vascular Study (OXVASC) were studied.

Study Conclusions:

In this population-based study of stroke etiology stratified by age, migraine was most strongly associated with cryptogenic TIA and ischemic stroke, particularly at older ages, suggesting a causal role or a shared etiology.

The Journal Club’s discussion of pros and cons of the study are found in the above Presentation Link.

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Can sudden unexpected death in epilepsy be prevented?

Presenter:  Adam Dickey, MD, PhD, PGY2 Neurology

Link to Presentation:  Journal Club June 2016

Clinical Question:

Do patients with refractory epilepsy show a lower incidence of SUDEP when receiving anti-epileptic drugs (AEDs) at efficacious doses than in those receiving placebo?

Journal Club Article:

Rivlin P, et al.  Risk of sudden unexpected death in epilepsy in patients given adjunctive antiepileptic treatment for refractory seizures: a meta-analysis of placebo-controlled randomised trials. Lancet Neurol. 2011 Nov;10(11):961-8.  PDF attached:  Rivlin et al

Methodology:

Searched Medline and the Cochrane Library for randomised trials investigating any AED in the add-on treatment of drug-resistant epilepsy in adults. Extracted the number and causes of death in patients allocated to AEDs at doses that were more efficacious than placebo against seizures, AEDs at non-efficacious doses, and placebo. In the study’s primary analysis, investigators compared the occurrence of definite or probable SUDEP between patients given efficacious AED doses and those given placebo using the Mantel-Haenszel method, with exclusion of trials with no event.

Study Conclusions:

Treatment with adjunctive AEDs at efficacious doses may have reduced the incidence of definite or probable SUDEP by more than seven times compared with placebo in patients with previously uncontrolled seizures. This result provides evidence in favor of active treatment revision for patients with refractory epilepsy.

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Does pioglitazone reduce the rates of stroke and myocardial infarction after ischemic stroke or TIA in select patients?

Presenter: Angela Aziz Donnelly, MD

Link to PowerPoint Presentation:  Journal Club Apr 2016

Clinical Question:

Does pioglitazone reduce the rates of stroke and myocardial infarction after ischemic stroke or TIA in select patients?

Journal Club Article:

Kernan WN et al.  Pioglitazone After Ischemic Stroke or Transient Ischemic Attack.  N Engl J Med, 2016 Apr 7;374(14):1321-31.  PDF attached: nejmoa1506930

Methodology:

In this multicenter, double-blind trial, 3876 patients were randomly assigned who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction.

Study Conclusions:

The risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo.  Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture.

  • Strict inclusion/exclusion criteria – e.g. no diabetes, no heart failure
  • Majority of population was white, male
  • Used HOMA-IR for measuring insulin resistance – how would we do this in clinical practice?
  • No comparison to lifestyle modifications
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Do the results of ictal SPECT add value beyond what is already learned by ictal scalp EEG and MRI?

Presenter: Aliza Sharon Kumpinsky, M.D.

Link to PowerPoint Presentation:  SPECT 3.3 edited

Clinical Question:

Do the results of ictal SPECT add value beyond what is already learned by ictal scalp EEG and MRI?   Will it change management?

Journal Club Article:

Velasko TR, et al.  Utility of ictal single photon emission computed tomography in mesial temporal lobe epilepsy withhippocampal atrophy: a randomized trial.  Neurosurgery. 2011 Feb;68(2):431-6: Utility of Ictal SPECT in MTLE with Hippocampal Atrophy

Methodology:

MTLE patients were randomly assigned to those with (SPECT, n = 124) and
without ictal SPECT (non-SPECT, n = 116) in an intent-to-treat protocol. Primary end
points were the proportion of patients with invasive EEG studies, and those offered
surgery. Secondary end points were the length of hospital stay and the proportion of
patients with secondarily generalized seizures (SGS) during video-EEG, postsurgical
seizure outcome, and hospital cost.

Study Conclusions:

Ictal-SPECT did not add localizing value beyond what was provided by
EEG-video telemetry and structural MRI that altered the surgical decision and outcome
for MTLE-HS patients. Ictal-SPECT increased hospital stay was associated with increased
costs and a higher chance of SGS during video-EEG monitoring. These findings support
the notion that a protocol including ictal SPECT is equivalent to one without SPECT in the
presurgical evaluation of adult patients with MTLE-HS.

 

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What are the neurological effects of levetiracetam as compared to carbamazepine in children with focal epilepsy?

Presenter: Rebecca Repasky Luke, M.D.

Link to PowerPoint Presentation: Journal Club Feb 2016

Clinical Question:

What are the neurological effects of levetiracetam as compared to carbamazepine in children with focal epilepsy?

Journal Club Article:

Jung da E, et al.  Neuropsychological effects of levetiracetam and carbamazepine in children with focal epilepsy.  Neurology. 2015 Jun 9;84(23):2312-9.

Methodology:

A total of 121 out of 135 screened  children (4-16 years) were randomly assigned to LVT or CBZ groups in a multicenter, parallel-group, open-label trial.  The study’s primary endpoints were defined as the end of 52 weeks of treatment, followed by analysis of changes observed in a series of follow-up neurocognitive, behavioral, and emotional function tests performed during treatment in the per protocol population.  Drug efficacy and tolerability were also analyzed among the intention-to-treat (ITT) population.

Study Conclusions:

Neither LVT nor CBZ adversely affected neuropsychological function in pediatric patients.  Both medications were considered equally safe and effective as monotherapy in children with focal epilepsy.

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Does endovascular intervention combined with medical management improve outcomes of patients with acute ischemic stroke?

Presenter: Erica Jones, M.D., M.P.H.

Link to PowerPoint Presentation: Journal Club

Clinical Question:

Does endovascular intervention combined with medical management, including IV tissue plasminogen activator, improve outcomes of patients with acute ischemic stroke?

Journal Club Article: 

Chen CJ, Ding D, Starke RM, Mehndiratta P, Crowley RW, Liu KC, Southerland AM, Worrall BB. Endovascular vs medical management of acute ischemic stroke.  Neurology. 2015 Dec 1;85(22):1980-90.

 

Methodology:
A systematic literature review was performed, and multicenter, prospective RCTs published from January 1, 2013, to May 1, 2015, directly comparing endovascular therapy to medical management for patients with acute ischemic stroke were included. Meta-analyses of modified Rankin Scale (mRS) and mortality at 90 days and symptomatic intracranial hemorrhage (sICH) for endovascular therapy and medical management were performed.

 

Study Conclusions:

This meta-analysis provides strong evidence that endovascular intervention combined
with medical management, including IV tissue plasminogen activator for eligible patients, improves the outcomes of appropriately selected patients with acute ischemic stroke in the setting of LVO.

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Nuedexta and its potential use for agitation in Alzheimer’s

Presenter: Deepa Panjeti-Moore

Clinical Question:

In a patient with Alzheimer’s disease-related agitation, does dextromethorphan hydrobromide-quinidine sulfate provide efficacy, safety, and tolerability.

Journal Club Article: 

Cummings, JL et al.  Effect of Dextromethorphan-Quinidine on Agitation in Patients With Alzheimer Disease Dementia: A Randomized Clinical Trial.  JAMA 2015 Sep 22-29;314(12):1242-54.

Methodology:

Phase 2 randomized, multicenter, double-blind, placebo-controlled trial using a sequential parallel comparison design with 2 consecutive 5-week treatment stages conducted August 2012-August 2014. Patients with probable Alzheimer disease, clinically significant agitation (Clinical Global Impressions-Severity agitation score ≥4), and a Mini-Mental State Examination score of 8 to 28 participated at 42 US study sites. Stable dosages of antidepressants, antipsychotics, hypnotics, and antidementia medications were allowed.

In stage 1, 220 patients were randomized in a 3:4 ratio to receive dextromethorphan-quinidine (n = 93) or placebo (n = 127). In stage 2, patients receiving dextromethorphan-quinidine continued; those receiving placebo were stratified by response and rerandomized in a 1:1 ratio to dextromethorphan-quinidine (n = 59) or placebo (n = 60).

The primary end point was change from baseline on the Neuropsychiatric Inventory (NPI)Agitation/Aggression domain (scale range, 0 [absence of symptoms] to 12 [symptoms occur daily and with marked severity]).

Study Conclusions:

In this preliminary 10-week phase 2 randomized clinical trial
of patients with probable Alzheimer disease, combination dextromethorphan-quinidine demonstrated clinically relevant efficacy for agitation and was generally well tolerated.

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