Justin, just your average teenage dirtbag, woke up as if nothing was wrong at 10 in the morning. He poured himself a bowl of delicious sugar-frosted sugar bombs and poured on the milk. Only when it kept falling out of his mouth did he notice something was not quite right. Picking up his phone, he took a quick selfie. One side of his face was drooping. He is only 14. Could he be having a stroke?
Bell palsy or Bell’s palsy?
All the great Persian physicians described facial nerve palsy back in the first millennium; it wasn’t until 1821 that Sir Charles Bell presented his thesis on the idiopathic paralysis of the facial nerve that bears his name. For some bizarre reason, some people like to call it Bell Palsy.
Facial (VII) nerve anatomy
The facial, or seventh cranial, nerve is responsible for sensory and motor innervation. It follows a complex anatomical course and innervates musculature derived from the second pharyngeal arch.
The functional components of the facial nerve are :
- General somatic afferent – sensory input of part of the external auditory meatus and part of the auricle
- Special afferent – taste from anterior two thirds of the tongue (ipsilateral)
- General visceral efferent – innervates lacrimal gland, submandibular and sublingual salivary glands, nasal + pharyngeal mucous glands
- Motor (branchial motor) – muscles of facial expression, stapedius, posterior belly of digastric and stylohyoid
Corticobulbar fibres project from the cerebral cortex and through the genu of the internal capsule before reaching the facial nerve nucleus within the pons. The facial nerve nucleus is divided into two, with the upper section being innervated by corticobulbar fibres from both cerebral hemispheres. The lower section is innervated solely by the contralateral cerebral hemisphere.
The facial nerve then arises from the lateral surface of the brainstem, between the pons and medulla oblongata. At its source, it consists of a large motor root and a smaller sensory root (also called the intermediate nerve).
Anatomical course of the facial nerve
- Motor and sensory roots cross the posterior cranial fossa and leave cranial cavity via the internal acoustic meatus (opening within the petrous part of the temporal bone)
- Enter facial canal where the two roots fuse to form the facial nerve
- Nerve enlarges to form geniculate ganglion
- Greater petrosal arises at this point (parasympathetic fibres to lacrimal gland and mucous glands of nose/maxillary sinus/palate
- Facial nerve continues along canal
- Motor nerve to stapedius
- Chorda tympani – sensation to anterior 2/3rd of tongue, parasympathetic innervation to submandibular +andsublingual glands
- Facial nerve then exits facial canal via the stylomastoid foramen (temporal bone)
- First extracranial branch – posterior auricular = motor innervation around ear,
Second extracranial branch🡪- motor innervation to posterior belly of digastric,
Third extracranial branch – motor innervation to stylohyoid muscle - The nerve, now termed the motor trunk, continues to the parotid gland (but does not innervate this) and splits into five branches which innervate muscles of facial expression
Temporal – Innervates muscles in the temple, forehead and supra-orbital area (frontalis, orbicularis oculi and corrugator supercilia)
Zygomatic – Innervates muscles in the infra-orbital area, lateral nasal area + upper lip (orbicularis oculi).
Buccal – Innervates muscles in the cheek, upper lip + corner of the mouth (orbicularis oris, buccinator and zygomaticus muscles).
Marginal Mandibular – Innervates muscles in the lower lip + chin (mentalis muscle).
Cervical – Innervates the platysma
Upper motor neurone vs lower motor neurone
Upper motor neurone lesions affect corticobulbar fibres above the facial nerve nucleus. There is bilateral innervation to the upper section of the nucleus; this is clinically important as it means that central lesions result in contralateral facial nerve paralysis with sparing of the forehead (the frontalis muscle).
Lower motor neuron lesions result in ipsilateral and complete facial nerve paralysis. Lacrimation and taste may or may not be affected depending upon the anatomical location of the insult (pre or post the greater petrosal and chorda tympani branches).
Around 50% of cases of paediatric facial nerve palsy are idiopathic (Bell’s Palsy) though one retrospective review found an incidence of 88%.
The differential diagnoses are broad, but it is vital to rule out an upper motor neurone lesion. These are often more sinister (malignancy, CVA, MS).
Differentials for lower motor neurone lesions
Congenital causes include birth trauma (forceps delivery), various syndromes (Moebius Syndrome – hypoplasia of motor nuclei, Goldenhar, syringobulbia and Arnold-Chiari malformations) and as well as genetic myopathies (myotonic dystrophy and myasthenia).
Acquired causes of facial nerve palsy
- Infection – Varicella (Ramsay-Hunt discussed below), Borrelia burgdorferi (particularly common in endemic areas with one study in Southampton (UK) finding that 42.5% of Lyme serology tests were positive in children with LMN facial nerve palsy), Herpes Zoster, Coxsackie, Mumps, CMV
- Complications of other infections – Acute/Chronic Otitis Media (rare now with an incidence of 0.005%), Meningitis, Mastoiditis
- Inflammatory conditions including vasculitis, HSP and Kawasaki
- Neoplasia – Schwannoma, Rhabdomyosarcoma, Histiocytosis, Leukaemia, Parotid Gland tumours
- Trauma – Temporal bone fractures
A bit more on Ramsay-Hunt syndrome
Ramsay-Hunt Syndrome, also known as herpes zoster oticus, is characterised by involvement of the seventh and eighth cranial nerves. Patients present with acute facial palsy +/- vestibulocochlear dysfunction with a vesicular rash over the auricula/external auditory meatus. Ramsay-Hunt is often very painful in the facial nerve distribution.
It appears to be more common in adolescents than younger children – causing 14% of facial palsies in those under 16 and 4.9% in those under 6. It is, however, less common than several other recognised infectious causes of facial nerve palsy, including Borrelia, HSV and adenovirus.
It is due to reactivation of latent VZV within the geniculate ganglion of the facial nerve. There is some evidence that VZV reactivation can be triggered by concurrent a EBV infection. Other causes are related to reduced cell mediated immunity.
VZV reactivation leads to inflammation of the motor branches of the facial nerve resulting in facial nerve palsy—reactivation within the sensory nerve results in the typical rash formation around the ear. Inflammation of the facial nerve can result in inflammation of the eighth cranial nerve (acoustic) by a bystander effect.
If a pregnant woman becomes infected with varicella, which results in foetal infection, the infant may develop Ramsay-Hunt Syndrome following reactivation.
Treatment of Ramsay-Hunt Syndrome includes aciclovir and prednisolone. The prognosis of Bell’s Palsy overall is good in children, with complete resolution of symptoms in the majority by six months. However, the prognosis of Ramsay-Hunt syndrome is worse and may be worse in children than in adults.
Treatment of Bells Palsy
Common practice is to treat Bell’s palsy with corticosteroids such as prednisolone. The aim is to minimise facial nerve swelling and compression within the temporal bone leading to long-lasting damage, reducing the time to recovery and increasing the chances of a complete recovery. The rationale for this treatment is an extrapolation from adult data, where up to 30% of untreated patients fail to recover completely. But does this hold true in children?
The prognosis of Bell’s Palsy overall is good in children, with complete resolution of symptoms in the majority by 6 months. The prognosis of Ramsay-Hunt syndrome is worse and may be worse in children than adults
Why is this important?
The incidence of Bell’s palsy has been reported at 18.8 per 100,000 in children and is more common in females. Bell’s palsy is the third most frequent stoke mimic in children, preceded only by migraine and seizure. Despite this, until 2022 there was only one randomised control trial (RCT) for the use of corticosteroids in children. This was an extremely small RCT of 42 children which found no significant improvement in outcome when corticosteroid treatment was initiated. However, at present we are operating in a grossly evidence free zone, making the BellPIC study, highly anticipated.
Babl FE, Herd D, Borland M, et al. Efficacy of Prednisolone for Bell Palsy in Children:
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial. Neurology. 2022 doi: 10.1212/WNL.0000000000201164
What did they look at?
The Paediatric Research in Emergency Departments International Collaborative (PREDICT) research network in Australia and New Zealand established the BellPIC study to investigate the utility of prednisolone in children with Bell’s palsy.
The primary outcome was complete recovery of facial function at 1 month rated on the House-Brackmann scale.
Secondary outcomes included facial function, adverse events and pain up to 6 months.
This was a double blinded, randomised, placebo-controlled superiority trial and compared 10 days of 1mg/kg/day of prednisolone (max dose 50mg) with placebo. To be included, children were aged from 6 months to <18 years with Bell’s palsy diagnosed in the ED by an Emergency doctor, with onset of facial weakness < 72 hours previous. There was a large number of contraindications for enrolment. These included contraindications to prednisolone (latent or active tuberculosis, systemic fungal infection, known hypersensitivity), active herpes zoster, use of any systemic or inhaled steroids within 2 weeks prior to the onset of symptoms and current or past oncological disease. This list is not exhaustive and the full exclusion criteria list can be found in the paper methodology. Block randomisation was used to ensure fair randomisation in each site.
Should we treat Bells palsy with steroids?
187 children were randomised: 94 to prednisolone and 93 to placebo. 13 participants had no primary outcome at 1 month, including 1 patient who did not receive any study drug. 174 patients were put forward for final analyses. The median age of participants in both arms of this study was 9.9 years and 11.1 years for the placebo and prednisolone group respectively. At 1 month, there was no significant difference in the proportion of patients who had recovered facial function to House-Brackmann grade 1 (49% in prednisolone vs 58% in placebo, not statistically significant). It is worth noting in the subgroup analyses, children >12 years had a slight (not-statistically significant) increase in recovery of facial function when treated with prednisolone (58% in prednisolone arms vs 50% in placebo arm).
Secondary outcomes included complete recovery of function using the House-Brackmann scale at 3 and 6 months and complete recovery using an alternative scale, known as the Sunnybrook scale, at 1, 3 and 6 months. The Sunnybrook scale is a regionally weighted scale of facial function and assesses resting symmetry, voluntary movement, and synkinesis. At 3 and 6 months there was no difference in in the proportion of participants with complete recovery when assessing all participant. Again, sub group analyses showed older children (>12 years) to trend towards increased recovery when treated with prednisolone compared with placebo. Recovery in children >12 years at 3 months was 94% in the prednisolone group versus 75% in the placebo group, and at 6 months was 97% versus 84% in prednisolone versus placebo.
A similar pattern of results was seen with complete recovery of facial function on the Sunnybrook scale.
Worryingly there is an increased concern that corticosteroid use may mask facial paralysis in Bell’s palsy as first presentation of an oncological diagnosis, both delaying diagnosis and potentially complicating management and prognosis. This event occurred in one patient enrolled in the RCT, and a further four patients screened as part of the RCT.
Limitations
The study was powered to find an increase in the proportion of complete recover of 12% more in the prednisolone group when compared with the placebo arm. Target recruitment was 540 (270 per group), with 244 subjects in each treatment group (allowing for a 10% dropout) needed to achieve 80% power and 5% significance. However, this study failed to achieve their desired sample size, despite extending the study by a year, and eventually enrolment stopped as funding stopped.
How good was the paper- CASP Checklist
Does the study address a clearly focused issue?
Yes
Was the cohort recruited in an acceptable way?
Yes, the eligible participants were identified in multiple sites and randomised in acceptable way.
Was the exposure accurately measured to minimise bias?
This study employed block randomisation, was double-blinded, placebo-controlled with the placebo taste-matched with the treatment group.
Have the authors identified all important confounding factors?
The authors repeated analyses of both primary and secondary outcomes adjusting for potential confounders such as age, sex, baseline severity of facial nerve dysfunction as time to treatment, presented as adjusted odds ratios.
Was the follow-up of the subjects complete and accurate?
13 of those randomised to placebo or treatment group were found to have no primary outcome recorded at 1 month and were therefore not included in the complete case analysis. In additions, 14 participants received less than all 10 required doses of the study drug and 5 participants receiving more than 10 doses of a study drug. One participant was diagnosed with leukaemia and was lost to follow up in terms of primary and secondary outcomes.
What were the results?
Despite the insufficient sample size this study suggested there is no more than a marginal likelihood that prednisolone is beneficial when used in Bell’s palsy in children.
Do you believe the results?
Yes
Can the results be applied to your local population?
These results can be applied to the Irish and UK context. One slight difference would be the presence of Lyme disease, present in Ireland and the UK, not seen in these study sites.
Do the results fit with other available evidence?
The results of this study fit with the small volume of evidence for the use of prednisolone in the paediatric population, reinforcing its lack of benefit.
This study provides provisional evidence that for children with Bell’s palsy, prednisolone does not significantly change recovery of complete facial function at one month.
A word from the author: Franz Babl
Thank you for this nice summary of the BellPIC study. We really tried hard to reach the recruitment target by extending the study in terms of sites and duration. To some degree our inability to reach target recruitment was due to children arriving with prednisolone already started by their general practitioners and late presentation of children – it can be difficult for parents to recognise facial asymmetry in Bell’s palsy, particularly in young children and when they are otherwise perfectly well. Jeffrey has summarised the main findings – that we found little evidence that treatment with prednisolone within 72 hours increased the rate of complete recovery of facial function by a clinically relevant amount. What remains unclear is at what age the transition to adult practice should occur – there is good evidence for the efficacy of steroid use in Bell’s palsy in adults. A careful assessment for alternative and oncological diagnoses should be conducted; especially if steroids are being considered a complete blood count should be performed.
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