SGEM#390: I Can’t Feel My Face when I Have Bell Palsy, but will Steroids Help?

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: The study population included or focused on those in the emergency department. Yes The patients were adequately randomized.  Yes The randomization process was concealed. Yes The patients were analyzed in the groups to which they were randomized. Yes The study patients were recruited consecutively (i.e. no selection bias). Unsure The patients in both groups were similar with respect to prognostic factors. Yes All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Yes All groups were treated equally except for the intervention. Yes Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. Yes The treatment effect was large enough and precise enough to be clinically significant. No 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.