Podcast: Play in new window | Download

Subscribe: RSS

Reference: Babl et al. Efficacy of prednisolone for bell palsy in children: a randomized, double-blind, placebo-controlled, multicenter trial (BellPIC). Neurology 2022

Date: January 3, 2023

Guest Skeptic: Dr. Jennifer Harmon is an MD, Ph.D at Children’s National Hospital in Washington, DC. She is a board-certified pediatric neurologist and completing another fellowship in medical genetics.

Dr. Jennifer Harmon

Case: A 9-year-old girl shows up at your emergency department (ED) with unilateral facial paralysis. Her parents noticed that one side of her face looked abnormal when she woke up in the morning. She has no other medical conditions and has not had any recent fevers, ear pain, or trauma. On exam, she is alert and active, but you note that the entire left side of her face does not move when you ask her to smile or raise her eyebrows. The remainder of her exam is unremarkable. You make a clinical diagnosis of Bell palsy, and the parents ask you, “Is there anything you can give her to help her recover faster?”

Background: Bell palsy is a common cause of unilateral facial 7th nerve palsy in children. The differential diagnoses for this presentation can include trauma, otitis media, viral infections (herpes, varicella, CMV, EBV, etc), brain lesions or stroke, and acute leukemia. If the 7th nerve palsy is known to be caused by the herpes virus it is called Ramsay Hunt syndrome (herpes zoster oticus) [1].

It is important to perform a careful history and physical before ultimately arriving at the diagnosis of Bell palsy. While many children spontaneously recover, the clinical manifestations of Bell palsy may significantly impact a child functionally and emotionally. 

There have been studies in adults regarding the treatment of Bell palsy that have demonstrated that treatment with corticosteroids provide significant benefit (NNT 10) [2].  The SGEM covered the use of steroids and antivirals for Bell Palsy in SGEM#14. Unfortunately, the data for the use of steroids in treatment of pediatric Bell Palsy is still lacking [3].

Clinical Question: Does prednisolone improve the proportion of children with Bell palsy with complete recovery at one month? 

Reference: Babl et al. Efficacy of prednisolone for bell palsy in children: a randomized, double-blind, placebo-controlled, multicenter trial (BellPIC). Neurology 2022

  • Population: Children 6 months to 18 years presenting to multiple emergency departments in Australia with Bell Palsy diagnosed by a senior clinician with onset of symptoms less than 72 hours prior to evaluation.
    • Excluded: There were a lot of exclusion criteria that we will list in the show notes.
      • Contraindication to prednisolone (active/latent tuberculosis, systemic fungal infection, hypersensitivity, diminished cardiac function, diabetes mellitus, peptic ulcer disease, chronic renal failure, multiple sclerosis, recent active herpes zoster or chickenpox)
      • Use of any systemic or inhaled steroid within 2 weeks prior to onset of symptoms
      • Current or past oncological diagnosis
      • Pregnant or breastfeeding
      • Receiving concomitant medications in which prednisolone is contraindicated
      • Immunization with a live vaccine within previous one month
      • Requirement for live vaccine within 6 weeks of first dose of study drug
      • Signs of upper motor VII nerve weakness
      • Acute otitis media concurrently or within 1 week prior to onset of symptoms
      • Vesicles at ear suggestive of Ramsay-Hunt syndrome
      • Known facial trauma within 1 week prior to symptom onset
      • Any other condition at risk of being influence by the study treatment or might affect completion of study
      • Any concern about ability to comply with the study protocol
      • Prior episode of Bell palsy
  • Intervention: Prednisolone 1 mg/kg (max 50 mg) for 10 days, with no taper.
  • Comparison: Placebo
  • Outcome: 
    • Primary Outcome: Complete recovery of facial function at 1 month defined by a House-Brackmann score of 1. This is a scale of 1 to 6 with 1 being completely normal function and 6 being complete paralysis. 

    • Secondary Outcomes: 
      • Recovery of facial function (House-Brackmann score = 1) at 3 and 6 months
      • Recovery of facial function (Sunnybrook scale score = 100) at 1, 3 and 6 months. This is a scale of 1 to 100 with 0 being completely normal function complete paralysis and 100 being normal function.
      • Self-reported (or parent-reported) pain at 1, 3 and 6 months
      • Presence of synkinesis or autonomic dysfunction at 1, 3 and 6 months using the Synkinesis Assessment Questionnaire (SAQ)
      • Ongoing palsy symptoms
      • Date of resolution of facial weakness
      • Emotional and functional wellbeing at 1, 3 and 6 months using the Pediatric Quality of Life Inventory (PedsQL) and Child Healht Utility 9D (CHU9D)
      • Adverse Outcomes
  • Trial: Double-blind, placebo-controlled, randomized, superiority trial

Authors’ Conclusions: “In children with Bell palsy, prednisolone does not significantly change recovery of complete facial function at one month. However, the study lacked the precision to exclude an important harm or benefit from prednisolone.”

Quality Checklist for Randomized Clinical Trials:

  1. The study population included or focused on those in the emergency department. Yes
  2. The patients were adequately randomized.  Yes
  3. The randomization process was concealed. Yes
  4. The patients were analyzed in the groups to which they were randomized. Yes
  5. The study patients were recruited consecutively (i.e. no selection bias). Unsure
  6. The patients in both groups were similar with respect to prognostic factors. Yes
  7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Yes
  8. All groups were treated equally except for the intervention. Yes
  9. Follow-up was complete (i.e. at least 80% for both groups). Yes
  10. All patient-important outcomes were considered. Yes
  11. The treatment effect was large enough and precise enough to be clinically significant. No
  12. Financial conflicts of interest. None

Results: There were 187 children randomized with 94 to prednisolone group and 93 to the placebo group. Median age was 9.9 years (IQR 5.1 to 12.9), 51.9% female, median time to treatment was 24 hours (IQR 11.5 to 48.0), and median House-Brackmann score at enrollment was 4 (IQR 3 to 4).

Key Results: In children with Bell palsy, the vast majority recover without treatment. 

Primary Outcome: At one month, 49% of patients receiving prednisolone had complete recovery compared to 58% in the placebo group.

Secondary Outcomes: 

  • Similar results seen when using Sunnybrook scale.
  • Synkinesis and pain were very low at all time points. 
  • Emotional wellbeing score not reported.
  • No serious adverse events; most common adverse events were behavior change and increased appetite.

1. Underpowered: This was a double-blinded, placebo controlled, randomized study but sadly (and the author’s acknowledge this), it was underpowered because they ran out of funding. Although they did not find evidence that early treatment with prednisolone improves complete recovery, the confidence intervals are pretty wide, so we need to interpret these results with caution.

2. Outcomes: The primary outcome was recovery from symptoms at one month. But is one month an appropriate follow up time for primary outcome? We see that at the one-month time frame, a higher percentage of children in the placebo group recovered compared to the children in the prednisolone group. However, when we look at the 3 month and 6 month follow up, this changes to where there is a higher percentage of children in the prednisolone group have symptom recovery. Again, we need to acknowledge that this is limited by the wide confidence intervals.

In patients with illnesses that can lead to lifelong facial differences, emotional well-being is an important factor and patient-oriented outcome. Our face is an important part of our social interaction so facial dysfunction may have a significant impact a child’s self-esteem and confidence. We were thrilled to see it was listed in secondary outcomes, but… it is not mentioned at all in the results. Moreover, 6 months may not be significant follow up time to determine true emotional impact to patient and family.

3. Exclusion Criteria: There was a long list of exclusion criteria for this study. Of the 869 patients assessed for eligibility, 78% were not enrolled. We acknowledge that some of the exclusion criteria were appropriate such as the contraindications to prednisolone therapy or oncological diagnosis or any signs pointing to an alternative diagnosis like Ramsay-Hunt syndrome, facial trauma, or otitis media. The criteria that I am slightly uncomfortable with are the patients who were excluded based on concern about ability to comply with study protocol. This seems to be a fairly subjective exclusion criteria that excluded 25 patients. In a study that was already underpowered, it’s unclear how these excluded patients would have impacted the results.

4. Interrater Reliability: The primary outcome for recovery was assessed using the House-Brackmann scale. The final grade was determined by clinicians from multiple specialties including neurology, otolaryngology, pediatrics, and emergency medicine. It is unknown how reliably they agree with one another on the grading. Previous research suggests that the inter-rater reliability may vary [4-7]. It is unclear how discrepancies in the grading may impact the primary outcome.

5. Differential Diagnoses for Facial Nerve Palsy: This paper made us a little nervous in its discussion of the wide range of other etiologies that should be considered before arriving at the diagnosis of Bell palsy. This included some scary stuff like acute leukemia in which we don’t want to accidentally give corticosteroids. One of the things that was notably absent was the consideration of Lyme disease. There have also been studies to suggest steroid use in Lyme disease associated facial palsy are associated with worse long-term outcomes [8]. 

All of these diagnoses may alter the risk/benefit ratio for treating with corticosteroids. The question of how corticosteroids impact Lyme disease associated facial nerve palsy is currently being studied by a Swedish group [9]. ED providers may want to consider mild expansion in workup (eg, CBC) to avoid usage in the vast minority of patients for whom steroids would be contraindicated.

Comment on Authors’ Conclusion Compared to SGEM Conclusion:  We generally agree with the authors’ conclusions. While many children with Bell palsy may experience spontaneous resolution with no intervention, this study was underpowered. Corticosteroid therapy in pediatric Bell palsy may offer a clinical benefit of long-term symptom resolution and positively impact a child’s emotional well-being. 

SGEM Bottom Line: The impact of corticosteroids in the treatment of pediatric Bell palsy is not known. 

Case Resolution: You explain to the family that there is some data in adults to suggest that corticosteroids may improve the chances of a complete recovery from Bell palsy. You acknowledge that the evidence for corticosteroid therapy is limited in the pediatric population and many children spontaneously recover. After reviewing the risks and benefits associated with treating their child with prednisolone, you and the family arrive at the shared decision to treat her with corticosteroids.

Clinical Application: Bell Palsy is a common cause of unilateral facial paralysis in children seen in the pediatric ED, and prednisolone is commonly used to help with symptom resolution. It may offer the potential benefit of long-term symptoms resolution although many children spontaneously recover. The risks and benefits should be explained to the family to come to a shared decision. It is also important to consider a wide range of differential diagnoses in patients presenting with unilateral facial nerve palsy. 

What Do I Tell the Patient/Parent? You have asked a fantastic question that I wish we knew the answer to. For adults, there are some studies that would suggest treatment with corticosteroids may improve likelihood of complete recovery from symptoms. However, the data surrounding the use of corticosteroids to treat Bell palsy in children limited. Many children recover spontaneously without any kind of intervention. Treatment with prednisolone may increases the chances that she will recover fully in the long term. The most side effects of treatment with corticosteroids are increased appetite and some behavioral changes. We can decide together what you would like to do.

Other FOAMed: 

  1. Peds EM Morsels: Facial Nerve Palsy
  2. RCEM Learning: Paediatric Presentations of Bell’s Palsy

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.

References:

  1. Sweeney CJ, Gilden DH. Ramsay Hunt syndrome. J Neurol Neurosurg Psychiatry. 2001;71(2):149-154.
  2. Madhok VB, Gagyor I, Daly F, et al. Corticosteroids for Bell’s palsy (Idiopathic facial paralysis). Cochrane Database Syst Rev. 2016;7:CD001942.
  3. Unüvar E, Oğuz F, Sidal M, Kiliç A. Corticosteroid treatment of childhood Bell’s palsy. Pediatr Neurol. 1999;21(5):814-816.
  4. Reitzen SD, Babb JS, Lalwani AK. Significance and reliability of the House-Brackmann grading system for regional facial nerve function. Otolaryngol Head Neck Surg. 2009;140(2):154-158.
  5. Jeong J, Lee JM, Cho YS, Kim J. Inter-rater discrepancy of the House-Brackmann facial nerve grading system. Clin Otolaryngol. 2022;47(6):680-683.
  6. Coulson SE, Croxson GR, Adams RD, O’Dwyer NJ. Reliability of the “Sydney,” “Sunnybrook,” and “House Brackmann” facial grading systems to assess voluntary movement and synkinesis after facial nerve paralysis. Otolaryngol Head Neck Surg. 2005;132(4):543-549.
  7. Kanerva M, Poussa T, Pitkäranta A. Sunnybrook and house-brackmann facial grading systems: intrarater repeatability and interrater agreement. Otolaryngol Head Neck Surg. 2006;135(6):865-871.
  8. Jowett N, Gaudin RA, Banks CA, Hadlock TA. Steroid use in Lyme disease-associated facial palsy is associated with worse long-term outcomes. Laryngoscope. 2017;127(6):1451-1458.
  9. Karlsson S, Arnason S, Hadziosmanovic N, et al. The facial nerve palsy and cortisone evaluation (Face) study in children: protocol for a randomized, placebo-controlled, multicenter trial, in a Borrelia burgdorferi endemic area. BMC Pediatr. 2021;21(1):220.