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Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
Bells palsy- To Treat or Not to Treat
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Bells palsy- To Treat or Not to Treat

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LMN Facial Palsy, Corticosteroids, Acyclovir

LMN Facial Palsy, Corticosteroids, Acyclovir

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  • Jackler p. 1234
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    • 1. Bell’s Palsy: To Treat or Not to Treat
    • 2. Road Map for the Session • • • • • Historical Perspective and Introduction Risk Factors Study Proper Strengths and Limitations Review of evidence
    • 3. Road Map for the Session • • • • • Historical Perspective and Introduction Risk Factors Study Proper Strengths and Limitations Review of evidence
    • 4. Early Treatment with Prednisolone or Acyclovir in Bell’s Palsy NEJM 2008;357;1598-607
    • 5. Historical Perspectives • Sir Charles Bell (1774-1842) – Studied facial anatomy extensively during Battle of Waterloo – Concluded that facial nerve controlled facial expression – “Respiratory nerve of the Face”
    • 6. Anatomy of Facial Canal Tympanic 1.53 mm Mastoid 1.48 mm Labyrinthine 1.02 mm 0.68 mm Coker NJ. Atlas of Otologic Surgery p.339
    • 7. Bell’s Palsy • • • • • • Idiopathic facial paralysis Diagnosis of Exclusion Most common diagnosis (> 60%) for acute facial palsy 30 per 100,000 Generally unilateral Rapid onset < 48 hours
    • 8. Complete Recovery 71 6 Peitersen E. Acta Otolaryngol 2002;549:4–30.
    • 9. Favorable prognosis for full recovery • • • • • Incomplete palsy Early recovery Young patients Normal taste, stapedial reflex, lacrimation Lack of post-auricular pain Peitersen E. Acta Otolaryngol 2002;549:4–30.
    • 10. Road Map for the Session • • • • • Historical Perspective and Introduction Risk Factors Study Proper Strengths and Limitations Review of evidence
    • 11. Postulated mechanism of Bell’s Palsy • Viral inflammatory/ immune mechanism – – – • HSV (based on serological evidence) HZV Other: CMV, EBV, adenovirus, rubella virus, mumps, influenza B, and coxsackievirus Alternate postulated mechanisms – Ischemia of the facial nerve – Hereditary predisposition
    • 12. Diabetes Mellitus • Bell’s patients with DM – 14 % (Korczyn AD ’71) – 21 % (Alford BR ’71) – 38 % (Yasuda K ’75) • • 66% demonstrate glucose intolerance Functional recovery poorer in diabetics
    • 13. Pregnancy • Incidence of Bell’s palsy 3-4 x higher (Hilsinger, Cohen et al.) • • • Third trimester with highest risk Higher risk of complete palsy Lower chance of complete recovery (Gillman et al.) • Preeclampsia 6 x prevalence in pregnant women with facial palsy
    • 14. Role of HSV-1 Murakami: Ann Intern Med, Volume 124(1).January 1, 1996.27-30
    • 15. Management of Bell’s Palsy • • Observation Medical Treatment – – • Surgery – – • Steroid Anti-viral agents Decompression Dynamic vs. static reanimation Facial Rehabilitation
    • 16. Road Map for the Session • • • • • Historical Perspective and Introduction Risk Factors Study Proper Strengths and Limitations Review of evidence
    • 17. Hypothesis • To determine whether Prednisolone or Acyclovir used early in the course of Bell’s Palsy improves the chances of recovery
    • 18. Selection of Subjects • • • • > 16 YO age Males and Females Presenting with unilateral facial nerve weakness of no identifiable cause who could be referred to collaborating ENT within 72 hours from the onset of symptoms 17 hospitals throughout Scotland serving 88% of total population
    • 19. Exclusion Criteria • • • • • • • • • • Pregnancy Breast-feeding Uncontrolled diabetes (Hgb A1C > 8%) Peptic Ulcer Disease Suppurative otitis media Herpes zoster Multiple Sclerosis Systemic infection Sarcoidosis and other rare conditions Inability to provide informed consent
    • 20. Study Design • • • • • Double-blind, placebo-controlled, randomized, 2 x 2 factorial trial Conducted from 6/2004 ~ 6/2006, f/u till 3/2007 for 9 month assessments Patients were recruited through their family doctors, emergency departments, the national 24-hour medical telephone consultancy service, and dentists’ office Referrals mainly from primary care to 17 hospitals serving 88% of total population in mainland Scotland Collaborating senior ENT confirmed eligibility
    • 21. Study Design • • • Patient was randomly assigned to a study group by an independent, secure, automated telephone-randomization service Patients underwent randomization twice which resulted in 4 study groups – Prednisolone + Placebo – Acyclovir + Placebo – Prednisolone + Acyclovir – Placebo + Placebo *Prednisolone (25mg PO BID) *Acyclovir (400mg PO 5X/Day) *Placebo (Lactose pill) Each patient received 2 bottles of odorless capsules with an identical appearance prepared by Tayside pharmaceuticals
    • 22. Enrollment & Outcomes 551 randomized Acyclovir (N=272) Placebo (N=279) Prednisolone (N=134) Placebo (N=138) Prednisolone (N=138) Placebo (N=141) Acyclovir + Prednisolone 124 completed Tx Acyclovir + Placebo 123 completed Tx Placebo + Prednisolone 127 completed Tx Placebo + Placebo 122 completed Tx
    • 23. Study Design • • • • • Patients were instructed to take the first dose of the study drug before leaving the hospital and the remaining doses at home during the next 10 days Within 3 to 5 days after randomization, a researcher visited patients to complete a baseline assessment Repeat visits to assess recovery occurred at 3 months If recovery was incomplete (> grade 2 on House-Brackmann scale), the visit was repeated at 9 months Compliance with the drug regimen was reviewed at the first visit and via telephone calls on day 7 after randomization and within a week after the last scheduled dose (day 10)
    • 24. Outcome Measurements • Primary outcome measure – House-Brackmann grading system for facial nerve function – Assigns to one of six categories with grade 1 indicating normal function – Assessed by documenting the facial appearance of patients in digital photographic images in four facial expressions: • At rest • Raised eyebrows • Eyes tightly closed • Forced smile – Graded by panel of 3 experts (ENT, Neurologist, Plastic surgeon), discrepancies were reassessed
    • 25. House-Brackmann Grading System Grade Gross characteristics Motion characteristics I. Normal Normal in all areas Normal in all areas II. Mild dysfunction Slight weakness noticeable on close Forehead: moderate to good III. Moderate dysfunction Obvious but not disfiguring difference Forehead: slight to moderate IV. Mod severe dysfunction Obvious weakness and/or disfiguring Forehead: none Eye: incomplete closure Mouth: asymmetry at rest V. Severe dysfunction Only barely perceptible motion Asymmetry at rest Forehead: none Eye: incomplete closure Mouth: slight movement VI. Total paralysis No movement No movement inspection May have slight synkinesis Normal symmetry and tone at rest between the two sides Noticeable but not severe synkinesis, contracture, or hemifacial spasm Normal symmetry and tone at rest asymmetry Normal symmetry and tone at rest function Eye: complete closure with minimal effort Mouth: slight asymmetry movement Eye: complete closure with effort Mouth: slight weak with maximum effort
    • 26. Outcome Measurements • Secondary outcomes – – – Health Utilities Index Mark 3 • System for classifying health-related quality of life status in 8 dimensions: vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain • Responses converted into single score ranging from -0.36 to 1.00 with 1 indicating full health Derriford Appearance Scale 59 • 59 questions covering aspects of self-consciousness and confidence • Scores range from 8 to 262 with higher scores indicating a greater severity of distress/ dysfunction Brief Pain Inventory • Measures both the severity of pain and the extent to which pain interferes with normal activities • Scores range from 0 to 110 with higher scores indicating greater severity
    • 27. Statistical Analysis • Compared primary outcome measure of complete recovery (grade 1 on House-Brackmann scale) at 3 months and 9 months using a two-sided Fisher’s exact test for: – – – – – • Prednisolone vs. no prednisolone Acyclovir vs. no acyclovir Prednisolone vs. Placebo Acyclovir vs. Placebo Prednisolone + Acyclovir vs. Placebo Prespecified secondary analyses compared scores with the use of t-tests (or Mann-Whitney tests in cases in which the data was not normally distributed)
    • 28. Study Population Baseline Characteristics of the Patients Characteristic Prednisolone (N=251) No Prednisolone (N=245) Acyclovir (N=247) No Acyclovir (N=249) Total (N=496) Sex – no. (%)  Male  Female 135 (53.8) 116 (46.2) 118 (48.2) 127 (51.8) 119 (48.2) 128 (51.8) 134 (53.8) 115 (46.2) 253 (51.0) 243 (49.0) Age - year 43.2±16.2 44.9±16.6 45.0±16.6 43.0±16.1 44.0±16.4 House-Brackmann Scale 3.5±1.2 3.8±1.3 3.6±1.3 3.7±1.2 3.6±1.3 Health Utilities Index Mark 3 Derriford Appearance Scale 0.80±0.22 71±37 10±18 0.78±0.21 75±41 16±21 0.79±0.21 72±39 12±18 0.78±0.22 74±38 14±21 0.79±0.22 73±39 13±20 120 (47.8) 95 (37.8) 147 (60.0) 64 (26.1) 137 (55.5) 130 (52.2) 267 (53.8) 59 Brief Pain Inventory Time between onset of Sx and Tx – no. (%)  Within 24 hours  >24 to ≤48 hours
    • 29. Adjusted Outcome Data Primary and Secondary Outcomes at 3 Months and 9 Months Variable Primary Outcome Measure1 Grade 1 on House-Brackmann Scale  At 3 Months  At 9 Months Seconday outcome Measures2 Prednisolone (N=251) No./Total No. 205/247 (83.0) 237/251 (94.4) Unadjusted No Prednisolone (N=245) Adjusted Odds Ratio (95% CI) P Value (%) Acyclovir (N=247) No./Total No. 152/239 (63.6) 200/245 (81.6) 2.44 (1.55–3.84) 3.32 (1.72–6.44) Mean <0.001 <0.001 Adjusted Beta 173/243 (71.2) 211/247 (85.4) Unadjusted No Acyclovir (N=249) Adjusted Odds Ratio (95% CI) P Value 184/243 (75.7) 226/249 (90.8) 0.86 (0.55–1.34) 0.61 (0.33–1.11) 0.50 0.10 Mean Adjusted Beta (%) Health Utilities Index Mark 3  At 3 Months  At 9 Months 0.91±0.17 0.84±0.26 0.91±0.13 0.88±0.16 −0.01±0.01 −0.06±0.03 0.40 0.04 0.90±0.16 0.86±0.21 0.92±0.14 0.88±0.19 −0.01±0.01 −0.02±0.03 0.32 0.38 Derriford Appearance Scale 59  At 3 Months  At 9 Months 42.4±32.3 40.0±36.1 43.2±33.4 49.9±35.5 1.72±2.88 −2.40±5.71 0.55 0.67 44.2±35.0 49.4±35.2 41.4±30.4 43.2±36.6 3.08±2.85 8.53±5.36 0.28 0.11 Brief Pain Inventory  At 3 Months  At 9 Months 1.51±6.41 1.36±5.29 2.04±8.14 1.83±6.37 −0.12±0.67 −0.08±1.02 0.85 0.94 1.83±7.00 1.61±5.87 1.72±7.62 1.72±6.19 0.13±0.66 0.05±0.96 0.84 0.96 For the primary outcome measure, odds ratios and P values have been adjusted for age, sex, the baseline score on the House-Brackmann scale, the receipt or nonreceipt of acyclovir and prenisolone, and the interval between the onset of symptoms and the initiation of a study drug 2. For the secondary outcome measures, odds ratios and P values have been adjusted for baseline measurement of age, sex, score on the House-Brackmann scale, the receipt or nonreceipt of acyclovir and prenisolone, and the time from the onset of symptoms to the initiation of treatment. **Beta regression coefficients were calculated by adjusted multiple regression analysis. 1.
    • 30. Summary of Table 2 • • • • • Statistically significant recovery rate between Prednisolone comparison groups at 3 months At 9 months, the rates of complete recovery were 94.4% for patients who received Prednisolone and 81.6% for those who did not, a difference of 12.8% points (95% CI, 7.2 to 18.4; P<0.001) No significant difference in complete recovery rates between the Acyclovir comparison groups For patients receiving double Placebo, 64.7% were fully recovered after 3 months, and 85.2% after 9 months Generally there were no significant differences among the groups in secondary outcome measures, including patients who received Prednisolone
    • 31. Proportion of normal facial function Figure 2. NEJM 2008;357;1605 at baseline, at 3 months, and at 9 months • Full recovery was defined as grade 1 on the HouseBrackmann facial nerve grading scale, which ranges from 1 to 6, with higher grades indicating worse facial paralysis.
    • 32. Adjusted Outcome Data Table 3. NEJM 2008;357;1604 Complete Recovery at 3 Months and 9 Months Variable (+) Prednisolone (−) Prednisolone Odds Ratio (95% CI) P Value Odds Ratio (95% CI) P Value At 3 Months (+) Acyclovir (−) Acyclovir 1.73 (0.96–3.12) 2.58 (1.37–4.88) 0.07 0.003 0.85 (0.49–1.47) 1.00 0.57 At 9 Months (+) Acyclovir (−) Acyclovir 1.76 (0.74–4.16) 3.23 (1.13–9.22) 0.20 0.03 0.58 (0.29–1.16) 1.00 0.12 • – – – – • Significance testing for comparisons at 3 and 9 months had the following results: combination therapy versus prednisolone only, P = 0.18 (3 months) and P = 0.28 (9 months) combination therapy versus acyclovir only, P = 0.004 (3 months) and P = 0.001 (9 months) acyclovir only versus double placebo, P = 0.79 (3 months) and P = 0.19 (9 months) prednisolone only versus double placebo, P<0.001 (3 months) and P = 0.004 (9 months) ** P values are for the comparison with double placebo Conclusion: Prednisolone was highly effective, both separately and in combination with Acyclovir. Acyclovir was ineffective, both separately and as an addition to Prednisolone.
    • 33. Discussion • • • • For patients receiving double Placebo, 64.7% of patients fully recovered at 3 months and 85.2% at 9 months, which shows a generally favorable outcome without treatment Early treatment (within 72 hours from onset of symptoms) with Prednisolone increased the rate of complete recovery to 83.0% at 3 months and 94.4% at 9 months Acyclovir produced no benefit over Placebo and there was no benefit in its addition to Prednisolone No benefits observed with respect to secondary outcome measures in any study group
    • 34. Discussion • • A total of 426 patients (86%) returned pill containers. Of these patients, – 383 (90%) returned empty containers, indicating complete compliance – 32 (8%) returned doses for 5 days or less – 11 (3%) patients returned doses for 6 days or more Dizziness was the most reported adverse reaction in all four study groups
    • 35. Road Map for the Session • • • • • Historical Perspective and Introduction Risk Factors Study Proper Strengths and Limitations Review of evidence
    • 36. Strengths • • • • Most patients recruited from primary care practices, thus reducing selection bias in hospital-based studies High rate of acceptance of randomization and low dropout rate during the study Since the study design was factorial, the power was the same for each pairwise comparison of treatment Drugs used in this study are relatively inexpensive and readily available
    • 37. Limitations • • • • • • • • Application in some populations with prevalent genetic polymorphisms? Could other environmental factors such as diet alter the response? House-Brackmann scale has been criticized for insufficient sensitivity to change and difficulty in assigning grades in patients with contrasting degrees of function in different parts of the face Previous h/o Bell’s Palsy (recurrence)? Drug compliance with Acyclovir? Age of study population? Outbreak of HSV or any signs of other viral infection prior to Bell’s Palsy? Any underlying diseases/ illnesses and possible drug interactions?
    • 38. Road Map for the Session • • • • • Historical Perspective and Introduction Risk Factors Study Proper Strengths and Limitations Review of evidence
    • 39. Cochrane review on Efficacy of steroids • • • • • • • • 4 trials of 179 patients Trial 1: Cortisone vs. placebo Trial 2: Prednisone + vitamins vs. vitamins Trial 3: High dose prednisone vs. saline Trial 4: Methylprednisolone Primary endpoint: VII recovery @ 6 mos Conclusions: NO significant benefit for giving steroids to Bell’s palsy patients Drawbacks: Individual studies underpowered. Steroid regimens differ.
    • 40. Efficacy of Steroid treatment • • • • • • • Prospective RCT 56 patients Arm I: Steroids Arm II: Placebo Success = HB I or II F/u @ 3 and 6 weeks No significant difference in response in the 2 groups Turk-Boru U et al. Kulak Burun Bogaz Ihtis Derg. 2005;14(3-4):62-6.
    • 41. Steroids in Complete paralysis • Meta-analysis of 3 prospective trials – 230 patients with HB VI • • • Treatment within 7 days of onset Total prednisone dose > 400 mg (405-425 mg) Complete Recovery: HB VI  I – Steroid group has 17% higher rate of CR than control (placebo/ no treatment) Ramsey MJ et al. Laryngoscope 2000; 110: 335-341
    • 42. Steroid vs. Steroid + Acyclovir • • • Double-blind RCT 99 Bell’s palsy patients – 53 treated with acyclovir- prednisone – 46 with placebo – prednisone – Prednisone dose 400 mg five times daily x 10 days Combined therapy is better in terms of: – Return of muscle motion – Prevention of partial nerve degeneration Adour KK 1996 Ann Otol Rhinol Laryngol. 1996 May;105(5):371-8
    • 43. Steroid vs. Steroid + Acyclovir • Prednisolone • Prednisolone + Valacyclovir • • Prospective RCT of 150 patients Prednisolone (20 tid x 5d, 10 tid x 3 d, 10 qD x 2 d) Predisolone + Valacyclovir (500 bid x 5 d) No significant difference in recovery Kawaguchi: Laryngoscope, Volume 117(1).January 2007.147-156
    • 44. History of Surgical Decompression Adour KK. 2002 Jan;259(1):40-7
    • 45. Controversy over Surgical Decompression • In favor of: – – – – – – – Gantz BJ ’99 Sillman JS ’92 Huges GB ’88 Goin DW ’82 Fisch U ’81 Brackmann DE ’80 Giancarlo HR ’70 • Against: – – – – – – – Adour KK ’01 Aoyagi M ’88 May M ’84 Gacek RR ’81 McNeill R ’94 Adour KK ’91 Mechelse K ’98
    • 46. Applications to Clinical Practice • • No data are available regarding how best to treat patients who present more than 72 hours from the onset of symptoms, so all patients with suspected Bell’s Palsy should be assessed as early as possible Withholding treatment will remain an appropriate strategy for some patients as most patients recover fully without any treatment
    • 47. Future Studies • • • Use of Valcyclovir 1g PO TID x 7 days since higher absorption and serum levels are possible than Acyclovir Exclusion of recurrent Bell’s Palsy Study in populations with prevalent genetic polymorphisms
    • 48. ANY QUESTIONS???

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