Journal ClubCase report and Research

66 year old male

8 hour history of R facial droop and numbness

Hypertension

Amlodipine 10mgLisinopril 20mgAspirin disp 75 mg

BP 180/110 Pulse 92

What is the differential diagnosis?

DifferentialCentral

Stroke/TIAMultiple SclerosisTumour

Peripheral

Bell’s PalsyLyme diseaseRamsay Hunt syndromeSarcoidosis, Guillain-BarréOtitis mediaTumour

How can you tell the difference?

Upper vs lower motor neurone lesion

Differentiating symptoms

Tick exposure, rash, arthralgiaHyperacusisAgeUnilateral/bilateralPainRate of onsetNeurological symptomsChange in mental state

Bell’s Palsy - neuronal inflammationUsually unilateral (R side 63%)

Posterior auricular pain (~ half)

Decreased tearing (~ sixth)

Hyperacusis (~ third)

Taste disturbances & reduced salivary flow

Sensory disturbance due to ?lack of mobility, ?5th nerve involvement

Highest incidence in >60s, pregnancy (3rd trimester), diabetes

Treatment

Steroids

Antivirals - HSV hypothesis

Meta-analysis

The benefits of steroids versus steroids plus antivirals for treatment of Bell’s palsy: a meta-analysisEudocia C Quant, neuro-oncology fellow,1,2 Shafali S Jeste, neurologist,3,2 Rajeev H Muni, ophthalmologist,4 Alison V Cape, maternal fetal medicine fellow,5,2 Manveen K Bhussar, clinical research assistant,6 Anton Y Peleg, research fellow and infectious diseases physician2,6,7

British Medical Journal 2009;339:b3354 doi:10.1136/bmj.b3354

Meta-analysis is a statistical synthesis of several trials addressing the same question

Is the question clearly stated?

To determine whether steroids plus antivirals provide a better degree of facial muscle recovery in patients with Bell’s palsy than steroids alone

Is the methodology described?How were the studies selected?

Detailed literature search for articles since 1984

Multiple search terms for online databases

Searching reference lists of systematic reviews

Two independent investigators

Was the literature search sufficiently rigorous?

No studies excluded on basis of language

Hand searching was not conducted of conference abstract books

Published articles only - discussed later

Grey literature - information produced on all levels of government, academics, business and industry in electronic and print formats not controlled by commercial publishing i.e. where publishing is not the primary activity of the producing body

Were the criteria for inclusion appropriate?

Included only RCTs that compared steroids with steroids and antivirals that had at least 1 month followup and assessment of recovery

Excluded trials involving animals, children and pregnant women

Avoided duplicating overlapping data sets from different papers

How was the quality of the studies assessed?

Jadad score evaluation

Randomisation process described and appropriate

Blinding process described and appropriate

Description of withdrawals and dropouts

Jadad score is the most widely used assessment for RCTs in the world

Score out of 5

Were the studies similar?Studies were selected on basis of steroids vs steroids + antivirals

Had to have at least 1 month of followup

Had to have score of degree of facial paralysis

Analysis of heterogeneity and factored into the statistics

Study qualityTime between symptom onset and treatmentLength of followupType of antiviral

Measure of heterogeneity

Ideally, the studies results included should all be undertaken in the same way. Study heterogeneity indicates that this ideal is not fully met.

I2 describes the percentage of total variation across studies that is due to heterogeneity rather than chance.

I2 = 47.1% suggests moderate heterogeneity

Random effects model

Statistical model in which both within-study error (variance) and between-studies variation (heterogeneity) are included in the assessment of confidence interval.

Gives wider confidence interval

Fixed effects model does not include between-studies variation

Cumulative forest plot analysis

What biases may affect results?

Lower quality studies were responsible for drawing the pooled odds ratio towards steroids + antivirals - one study removed analysis

Publication bias - funnel plot

Sources of heterogeneity - Random effects model used, Subgroup analysis

Cumulative odds ratio

One study removed analysis

Funnel plot to assess publication bias Standard error measures of the precision of the studyTrim & fill method aims to identify and correct for funnel plot asymmetry

Subgroup analysis

Earlier treatment - within 3 days vs. after 3 days

Longer followup - < 3 months vs. >3 months

Type of antiviral

Other sources of biasSeverity of facial paralysis differed between studies- one study may suggest that antivirals helped those with most severe paralysis, contradicted by another

Differences in primary end point - complete vs. partial recovery. Reference to other smaller studies not included in meta-analysis

Theoretical problem Zoster sine herpete - would require higher doses than in studies

Different types of antivirals - Valaciclovir/famciclivir have better bioavailability

Does this review help to answer the key question?

To determine whether steroids plus antivirals provide a better degree of facial muscle recovery in patients with Bell’s palsy than steroids alone

Would you give antivirals?