A meta-analysis and modelling of the duration of symptoms in Bell’s palsy in the Scottish and Scandinavian trials

A meta-analysis and modelling of the duration of symptoms in Bell’s palsy in the Scottish and Scandinavian trials | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A meta-analysis and modelling of the duration of symptoms in Bell’s palsy in the Scottish and Scandinavian trials William Kingston, Thomas Berg, Frank Sullivan, Fergus Daly This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7355290/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 13 You are reading this latest preprint version Abstract Background Idiopathic peripheral facial paralysis (Bell’s palsy) is commonly treated with corticosteroids and sometimes with antiviral therapy in combination. The benefits of corticosteroids for long term complete recovery are well established but the effect of treatment and different treatment combinations on duration of disease are not well discussed in the literature and so is the focus of this investigation. Methods Two randomised controlled studies that were broadly similar in their objectives (being primarily the chances of recovery by end of study), design (different treatment combinations that were very similar in both studies), instruments (measurement of severity), delivery (a visit regime over approximately one year) and in their consideration of outputs (proportion recovered) additionally provided sufficient data for a secondary investigation of duration of symptoms. Probability models for duration were compared and the best-fitting model was selected. Results A significant reduction in median time to recovery after treatment with prednisolone was identified, compared with treatment without prednisolone (54 days vs. 95 days: significance probability SP < 0.0001). Antivirals had no observable effect on time to recovery whether considered alone (101 days vs. 90 days; SP = 0.571) or in combination with prednisolone (53 days vs. 54 days; SP = 0.750). The fitted model was used to provide estimated quantiles and estimates of recovery rates at key intervals. Conclusion These results amplify those previously identified when exploring achievement of final recovery but provide an important additional information about the rate of recovery to patients concerned about their immediate prognosis, and to aid patients and practitioners in their discussion of treatment options. Figures Figure 1 Figure 2 Figure 3 Background Idiopathic unilateral facial weakness (Bell’s palsy) occurs in approximately 11 to 40 per hundred thousand patients per year, equivalent to a lifetime chance of 1 in 60 of experiencing this condition (Holland 2014 [ 1 ]). Many episodes will be transient over several weeks or months (prognoses vary) and with a good chance of complete recovery. Even in the two studies considered here there was considerable variation in clinical outcome. Commonly prescribed treatments are steroid therapy, possibly in combination with antivirals; but also include electrotherapy, physical therapy, acupuncture, “do nothing”; and in some cases, surgery may be considered (Rothel 2023 [ 2 ], de Almeida 2014 [ 3 ], de Almeida 2009 [ 4 ], Kim 2020 [ 5 ]). Many patients’ concerns are focused on the chances of making a full recovery, but because of the contemporaneous and not necessarily short-term consequences of the disease on social activity, attendance at their place of employment, associated symptoms possibly including pain, interference with day-to-day activity, and overall perturbation of general well-being, a secondary important consideration is the duration of symptoms and debility. There is little guidance available in the public domain and what there is, is often vague, making it difficult for patients to gain a good understanding of their condition. For example the NHS offers “ Your Bell’s palsy symptoms should get better within 6 months, but it can take longer for some people ” (NHS 2023 [ 6 ]). Consider also “ 71% [of patients] show obvious signs of recovery within 3 weeks. If individuals do not improve in the first few weeks, their recovery may take longer ” (Medical News Today 2023 [ 7 ]). A third source suggests that “ Bell’s palsy often goes away on its own within 1 to 2 months ” (Amer Acad Fam Phys 2022 [ 8 ]). Methods The sources of this investigation are two clinical trials both investigating the recovery rate of patients diagnosed with Bell’s palsy following treatment commencing within 72 hours of onset of symptoms with either: antivirals, corticosteroid, a combination therapy or a placebo. The trials were carried out in Scotland and in Sweden and reported in close conjunction (Sullivan 2007 [ 9 ], Engstrom 2008 [ 10 ]). Ongoing measurement of severity used the same study instrument being the House-Brackmann grading system (House 1985 [ 11 ]) and adopted a similar threshold for attainment of recovery (House-Brackmann grade 1). Moreover, both studies adopted a visit schedule that permitted some insight into the duration of symptoms including a final visit at which recovery might still not have been achieved, providing a trial completion status for all patients. In both studies, patients exhibiting symptoms of a recent onset of Bell’s palsy with a clinical diagnosis were recruited. After an exploration of inclusion-exclusion criteria and an initial assessment of severity of symptoms using the House-Brackmann scale, patients were randomised with equal likelihood to one of four treatment options: steroid alone, antiviral alone, steroid-antiviral in combination, or to placebo. In all cases, regular planned assessments using the same scale were made according to a visiting schedule up to complete recovery or assessment at a final visit. Both studies were centred around end-of-study status and a consequent treatment recommendation. The known visit schedule together with the recorded account of patient progress at each visit enables the exploration of symptom duration. The studies are described in detail in their respective primary publications ([ 9 ], [ 10 ]). Written informed consent was obtained at the time from all participants. For both studies, ethical approval was obtained from their respective national committees. The University of St Andrews Ethics Committee approved this meta-analysis. Both studies recruited adults who were referred from emergency departments or general practitioners after a diagnosis of acute, unilateral, peripheral facial palsy. Engstrom additionally recruited patients who sought care directly. Sullivan followed 496 patients to completion with assessments at onset, and as close to 3 months and 9 months as could be achieved. Dates of assessments were recorded to the day. Engstrom followed 829 patients to completion with assessments at 11–17 days and thereafter at 1, 2, 3, 6 and 12 months. In both original studies, all patients, prescribers, assessors and data analysts were blinded to treatment allocation until statistical analysis was completed following database lock. For the purposes of this analysis we omitted three patients with very late final assessments perturbing an assessment of disease duration, and a 4th patient whose disease trajectory strongly suggested a misdiagnosis of Bell’s palsy Thus altogether the two trials yielded a combined database of 1321 observations of disease duration, stratified by initial treatment allocation. There were two notable differences identified between the two studies, one in design and one in the emerging final outputs. First: the antiviral compounds were acyclovir for the Sullivan study and valacyclovir for the Engstrom study. Sullivan used acyclovir at a dose of 2000mg for 10 days giving a total dose of 20g. The valacyclovir dose used by Engstrom was two 500mg tablets three times a day for 7 days giving a total dose of 21g. However, the main observation of the pharmacokinetics of the two drugs is the difference in oral bioavailability of acyclovir. Valacyclovir is rapidly hydrolysed after oral administration to form acyclovir, resulting in an acyclovir bioavailability of 3 to 5 times that of oral acyclovir (Miserocci 2007 [ 12 ], Patel 1997 [ 13 ]). The plasma concentration of acyclovir following oral administration of valacyclovir is similar to that achieved with intravenous acyclovir (Wei 2021 [ 14 ]). This means that whilst the original doses seem similar (within 5% of each other) the resulting plasma concentration of antiviral will have been greater in the Engstrom trial. Both steroid compounds were prednisolone; indistinguishable placebo compounds were lactose. The prednisolone dose was 25mg twice daily for 10 days giving a total dose of 500mg (Sullivan) or 12 x 5mg tablets for the first 5 days and then reduced by 10mg per day over a total treatment time of 10 days giving a total dose of 450mg (Engstrom). Second: notwithstanding the difference in antiviral treatment one might reasonably have anticipated the patient experience on placebo and on steroid alone to be broadly indistinguishable: in fact in Sullivan’s study, 104 of 122 patients on placebo (85%) were recovered at 9 months, along with 122 of 127 patients on prednisolone alone (96%). In Engstrom’s study, after 12 months’ observation, the respective rates were 133/206 (65%) and 160/210 (76%). So, across both treatment regimes, and even with a longer assessment period that might have permitted a greater opportunity for recovery, the progress achieved was significantly lower for Engstrom’s study ( p < 0.001 on placebo, and also on prednisolone). Possible rationales for these observed differences include some previously unremarked distinction in genetic make-up, environmental differences, properties of the two different antivirals, or even in the application of the House-Brackmann instrument, though this measure is widely used because of its ease and consistency. The broad similarities in outcome between the two studies were nevertheless striking. Both studies demonstrated significant benefit in overall recovery for patients receiving prednisolone compared with those not ( p < 0.0001); and no benefit in either case from either antiviral compound (Sullivan SP ~ 0.07, Engstrom SP ~ 0.65). Drug interaction was insignificant in both studies. The two study databases were merged into a single spreadsheet and the combined dataset was then modelled for time to recovery. The visit schedule in both studies meant that a determination of recovery to the exact day was not possible, only that recovery occurred over some known interval (or not at all). The interval data do not in themselves render any difficulty with the estimation of quality of fit or of the associated model parameters; however, the highly aggregated data for both studies blurs any convincing individual best fit. Amongst the usual competitors (exponential, Weibull, Gompertz, lognormal) the exponential fit had a significantly larger deviance across all treatments (i.e. the worst-fitting model considered); there was little to choose between the other three potential models though the lognormal fit, possessing the smallest deviance (Akaike 1973 [ 15 ]) was marginally best across all treatments. Considered together with the very substantial advantage that application of this model permits an easy assessment of differences and their significance based on normal distribution theory, this was the model selected. Once established, the model was used to compare the distribution of time to recovery between the 4 treatment arms as well as direct comparison between those that received prednisolone and those that did not, and those that received antivirals against those that did not. Time to recovery, rather than the achievement of recovery, was the primary focus of the analysis. Timelines illustrating recovery probability were then created from these probability models displaying likelihood of recovery at key time markers (30, 60, 90, 180, 270 and 360 days). Results The merged dataset was made up of 1321 patients (829 from the Engstrom study, 492 from the Sullivan study) stratified by initial treatment allocation and displaying the time between presentation and the first assessment to have recovered according to the House-Brackman scoring system. Of those 1321, 298 (22.49%) were not observed to have recovered within the observation periods of the original studies. Probability modelling generated the following Figures 1, 2 and 3 displaying the proportion of each treatment group that is expected to have recovered with reference to time since initial presentation and treatment. From these figures was extracted the probability of recovery at certain arbitrary time points, 30, 60, 90, 180, 270 and 360 days respectively (see Table 1); and for each group quartile-recovery dates were also identified from the fitted model (see Table 2). Table 1: Proportion recovered at notable prognostic time intervals by treatment allocation. Recovery Rate (%) Treatment Day 30 Day 60 Day 90 Day 180 Day 270 Day 360 AP 35.2 53.1 63.5 78.8 85.7 89.5 AO 26.6 39.5 47.7 61.8 69.5 74.5 OP 35.2 52.8 63.1 78.4 85.3 89.2 OO 27.6 41.3 50.0 64.7 72.5 77.4 A 30.7 45.9 55.2 70.2 77.7 82.4 Not A 31.3 46.8 56.4 71.5 79.1 83.6 P 35.2 52.9 63.3 78.6 85.5 89.4 Not P 27.1 40.4 48.9 63.2 71.0 76.0 Table 2: Duration in days for each quartile to recover depending on treatment allocation. Quartiles (days) Treatment Q 0.25 Q 0.50 (median) Q 0.275 AP 19 53 149 AO 27 101 371 OP 19 54 152 OO 26 90 312 A 22 72 231 Not A 22 69 215 P 19 54 150 Not P 27 95 340 Discussion The argument for antivirals Whilst the aetiology of Bell’s palsy remains elusive, one school of thought holds that herpes (Herpes simples virus type 1 and Herpes zoster virus are both cited as possible causative agents) viral reactivation in the geniculate ganglion of the facial nerve could be the cause via inflammation and nerve compression within the narrow fallopian canal (Loukas 2014 [ 16 ]). Following this, prescription of acyclovir was considered to combat viral load. Early studies supported the use of antivirals in combination with corticosteroids (Shahidullah 2011 [ 17 ]); and in 2014 the Bell’s Palsy Working Group of the Canadian Society of Otolaryngology published guidelines encouraging co-prescription of antiviral and corticosteroids for severe and complete cases of facial paralysis (de Almeida [ 3 ]). The American Academy of Otolaryngology similarly published guidelines suggesting co-prescription as an option as antivirals offered ‘small potential improvement in facial nerve function’ (Baugh 2013 [ 18 ]). Several online sources of medical advice intended for healthcare professionals still suggest that prescribing antivirals such as acyclovir ‘ may be reasonable’ (Grogan 2001 [ 19 ], Taylor 2021 [ 20 ]); yet more recent studies fail to find any benefit by their inclusion in treatment Marques Gomes 2024 [ 21 ]). However, with possible side effects of antivirals such as acyclovir including diarrhoea and vomiting and, in rare cases, hepatic disorders and renal impairment, it is important that antivirals are only prescribed if they will give therapeutic benefit (Joint Formulary Committee [ 22 ]). This study has formed and then statistically analysed a large database of patients from controlled trials looking at the efficacy of different treatment regimens for Bell’s palsy. This study focused on both absolute probability of recovery and median time to recovery. These are important factors as knowledge of prognosis depending on treatment will help dictate regimes chosen by patients. Treatment with prednisolone gave a significant increase in overall recovery probability and reduced the median time to recovery. Antiviral therapy had no effect on likelihood of recovery or duration of disease. Combination therapy was no more effective than corticosteroid monotherapy across either metric. Efficacy of Antiviral therapy - There was no discernible difference in overall recovery probability or in median duration of disease between participants who received Antivirals and those who did not (A vs Not A SP = 0.693) as shown in Fig. 3 and Table 2 . Efficacy of Corticosteroid therapy – There is a significant increase in overall recovery probability when treated with prednisolone (P vs not P) for overall recovery probability SP < 0.0001). Likewise, there is a significant reduction in median time to recovery for the patients who received prednisolone compared to those who received only antiviral or placebo treatments. Again a consideration of P vs Not P, but through a comparison of median time to recovery not overall recovery chance (SP < 0.0001) as demonstrated in Fig. 2 and Table 2 . Efficacy of dual therapy - There was also no difference in either overall recovery probability or median time to recovery between the group given a combination of corticosteroid + antiviral and the group given corticosteroid + placebo This is AP vs OP. and is intended to highlight that there is no evidence of synergistic effect (SP 0.750) Shown in Fig. 1 and Table 2 – there is no divergence between treatment groups AP and OP. Strengths and limitations Both studies were designed for maximum generalisability and used common and moderately inexpensive easily available treatment compounds. By merging the databases we have increased the potential for convincing argument. The methodology adopted for their analysis is conventional and well-known, and has yielded conclusive results. This meta-analysis has produced easy to understand timelines of predicted recovery probability which are intended to ease decision making for patients affected by Bell’s palsy. Although the reasons are different and inherent in their design, both studies lack the intensive monitoring of individual patient progress during the early period between onset and 3 months (or possibly 4) that would illuminate the critical interval over which the majority of recoveries across all treatments and combinations is achieved. A future study whose focus was on disease duration rather than whether resolution occurs at all would need a greater frequency of assessments to provide a better estimation of disease duration. The patient demography in both studies was not distinguished in any important characteristic. The Scandinavian study extended over a longer time frame than the Scottish study allowing, in principle, a greater opportunity for recovery to occur. However, one might have anticipated broadly similar outcomes, even if only in the double-placebo (OO) and steroid-only (OP) groups. In fact there were surprising and significant differences. We have not adequately explained the differences in overall rates of recovery that have been referenced for the two studies. It may be that the higher bioavailability of the antiviral drug in the Engstrom study had a negative effect. Neurotoxicity has been reported with Acyclovir, though it is not well understood [ 21 ]. We remain confident that the similarities in design, delivery and outcome for these two studies offer more encouragement for the principle of merging than the differences offer against it. Conclusion We have identified an important practical issue (patients’ concerns about disease duration) and the principle of its resolution. The data have provided meaningful and easily conveyed estimates that can usefully be shared with patients concerned about their chances of recovery and the time that that recovery might take, which enable an informed choice of treatment pathway. We have also shown that antiviral adjunct therapy has no effect on duration of disease. Declarations Ethics approval and consent to participate Ethical approval for analysis of secondary data was granted by the University of St Andrews ethics committee. Written informed consent was obtained from participants before inclusion in the original studies. Consent for publication Consent for publication of results was obtained from participants before inclusion in the original studies. Competing interests The authors declare no competing interests. Funding William Kingston received funding from the University of St Andrews to complete this research. Availability of data and materials The data underlying this study are available on request to the corresponding author, Professor Fergus Daly - [email protected] . References Holland NJ, Bernstein JM. Bell's palsy. BMJ Clin Evid [Internet]. 2014 [cited; 2014. Ronthal M. 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Grogan PM, Gronseth GS. Practice parameter: Steroids, acyclovir, and surgery for Bell’s palsy (an evidence-based review) [RETIRED]. Neurology [Internet]. 2001 [cited; 56(7):830-6. Available from: doi:10.1212/WNL.56.7.830. Taylor DC. Bell Palsy Treatment & Management: MedScape. 2021 [Available from: https://emedicine.medscape.com/article/1146903-treatment#d10. Marques Gomes P, Cunha Cabral, D., Alves Carção A., Ferreira PeneÌ‚da J., Duarte, D., & Azevedo, P. Prognostic Factors for Recovery in Bell’s Palsy. . ENT Updates, 14(2), 32–36 [Internet]. 2024 [cited. Available from: https://doi.org/10.5152/entupdates.2024.24363. Joint Formulary Committee. British National Formulary (online) London: BMJ and Pharmaceutical Press [Accessed on [02/10/2024]]. Additional Declarations No competing interests reported. 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15:49:52","extension":"xml","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":76739,"visible":true,"origin":"","legend":"","description":"","filename":"583eccdd8ce649a78ad5879ada8f9f841structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7355290/v1/f433f5079e254a1563f9abeb.xml"},{"id":92101759,"identity":"ec0fd7d0-8b88-4288-812f-cfef457703d3","added_by":"auto","created_at":"2025-09-24 15:49:52","extension":"html","order_by":18,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":90553,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7355290/v1/5f2a3c51a0aba7a282a06ff6.html"},{"id":92102997,"identity":"a52eccc6-7eaa-4247-b1fe-9ebb50895a5b","added_by":"auto","created_at":"2025-09-24 16:05:52","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":56820,"visible":true,"origin":"","legend":"\u003cp\u003eFitted lognormal distribution of Recovery Probability by Treatment Group. (A = Antiviral, P= Prednisolone, O = Placebo)\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7355290/v1/23daefb13be797d3cfd5cacd.png"},{"id":92101740,"identity":"68a7b0ef-fb77-4b5c-998e-6804e7d8fbcf","added_by":"auto","created_at":"2025-09-24 15:49:52","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":25368,"visible":true,"origin":"","legend":"\u003cp\u003eFitted lognormal distribution of recovery probability by involvement of prednisolone (P = Prednisolone, NotP = no prednisolone used)\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7355290/v1/b03a893a6b34710e76babee5.png"},{"id":92101742,"identity":"00dc8d86-075c-4095-b557-05702ab2bbf3","added_by":"auto","created_at":"2025-09-24 15:49:52","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":25466,"visible":true,"origin":"","legend":"\u003cp\u003eFitted lognormal distribution of Revery Probability by involvement of Antivirals (A = Antivirals, NotA = No antivirals used)\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7355290/v1/50ff2a04dd4668a7814c7420.png"},{"id":92103789,"identity":"1c51f0e8-a0e7-4e34-b9ee-2c8847d16f5a","added_by":"auto","created_at":"2025-09-24 16:13:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":780402,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7355290/v1/d159bbcf-db0c-4652-a6c8-469a88067aa1.pdf"},{"id":92101761,"identity":"636e1126-76ef-477b-b260-2e179812465b","added_by":"auto","created_at":"2025-09-24 15:49:52","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":264192,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix.docx","url":"https://assets-eu.researchsquare.com/files/rs-7355290/v1/1111e9b760747fb95d43e38f.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"A meta-analysis and modelling of the duration of symptoms in Bell’s palsy in the Scottish and Scandinavian trials","fulltext":[{"header":"Background","content":"\u003cp\u003eIdiopathic unilateral facial weakness (Bell\u0026rsquo;s palsy) occurs in approximately 11 to 40 per hundred thousand patients per year, equivalent to a lifetime chance of 1 in 60 of experiencing this condition (Holland 2014 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]). Many episodes will be transient over several weeks or months (prognoses vary) and with a good chance of complete recovery. Even in the two studies considered here there was considerable variation in clinical outcome. Commonly prescribed treatments are steroid therapy, possibly in combination with antivirals; but also include electrotherapy, physical therapy, acupuncture, \u0026ldquo;do nothing\u0026rdquo;; and in some cases, surgery may be considered (Rothel 2023 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], de Almeida 2014 [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], de Almeida 2009 [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], Kim 2020 [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]).\u003c/p\u003e\u003cp\u003eMany patients\u0026rsquo; concerns are focused on the chances of making a full recovery, but because of the contemporaneous and not necessarily short-term consequences of the disease on social activity, attendance at their place of employment, associated symptoms possibly including pain, interference with day-to-day activity, and overall perturbation of general well-being, a secondary important consideration is the duration of symptoms and debility.\u003c/p\u003e\u003cp\u003eThere is little guidance available in the public domain and what there is, is often vague, making it difficult for patients to gain a good understanding of their condition. For example the NHS offers \u0026ldquo;\u003cem\u003eYour Bell\u0026rsquo;s palsy symptoms should get better within 6 months, but it can take longer for some people\u003c/em\u003e\u0026rdquo; (NHS 2023 [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]). Consider also \u0026ldquo;\u003cem\u003e71% [of patients] show obvious signs of recovery within 3 weeks. If individuals do not improve in the first few weeks, their recovery may take longer\u003c/em\u003e\u0026rdquo; (Medical News Today 2023 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]). A third source suggests that \u0026ldquo;\u003cem\u003eBell\u0026rsquo;s palsy often goes away on its own within 1 to 2 months\u003c/em\u003e\u0026rdquo; (Amer Acad Fam Phys 2022 [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]).\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe sources of this investigation are two clinical trials both investigating the recovery rate of patients diagnosed with Bell\u0026rsquo;s palsy following treatment commencing within 72 hours of onset of symptoms with either: antivirals, corticosteroid, a combination therapy or a placebo. The trials were carried out in Scotland and in Sweden and reported in close conjunction (Sullivan 2007 [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], Engstrom 2008 [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]).\u003c/p\u003e\u003cp\u003eOngoing measurement of severity used the same study instrument being the House-Brackmann grading system (House 1985 [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]) and adopted a similar threshold for attainment of recovery (House-Brackmann grade 1). Moreover, both studies adopted a visit schedule that permitted some insight into the duration of symptoms including a final visit at which recovery might still not have been achieved, providing a trial completion status for all patients.\u003c/p\u003e\u003cp\u003eIn both studies, patients exhibiting symptoms of a recent onset of Bell\u0026rsquo;s palsy with a clinical diagnosis were recruited. After an exploration of inclusion-exclusion criteria and an initial assessment of severity of symptoms using the House-Brackmann scale, patients were randomised with equal likelihood to one of four treatment options: steroid alone, antiviral alone, steroid-antiviral in combination, or to placebo. In all cases, regular planned assessments using the same scale were made according to a visiting schedule up to complete recovery or assessment at a final visit. Both studies were centred around end-of-study status and a consequent treatment recommendation. The known visit schedule together with the recorded account of patient progress at each visit enables the exploration of symptom duration.\u003c/p\u003e\u003cp\u003eThe studies are described in detail in their respective primary publications ([\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]). Written informed consent was obtained at the time from all participants. For both studies, ethical approval was obtained from their respective national committees. The University of St Andrews Ethics Committee approved this meta-analysis.\u003c/p\u003e\u003cp\u003eBoth studies recruited adults who were referred from emergency departments or general practitioners after a diagnosis of acute, unilateral, peripheral facial palsy. Engstrom additionally recruited patients who sought care directly. Sullivan followed 496 patients to completion with assessments at onset, and as close to 3 months and 9 months as could be achieved. Dates of assessments were recorded to the day. Engstrom followed 829 patients to completion with assessments at 11\u0026ndash;17 days and thereafter at 1, 2, 3, 6 and 12 months. In both original studies, all patients, prescribers, assessors and data analysts were blinded to treatment allocation until statistical analysis was completed following database lock.\u003c/p\u003e\u003cp\u003eFor the purposes of this analysis we omitted three patients with very late final assessments perturbing an assessment of disease duration, and a 4th patient whose disease trajectory strongly suggested a misdiagnosis of Bell\u0026rsquo;s palsy Thus altogether the two trials yielded a combined database of 1321 observations of disease duration, stratified by initial treatment allocation.\u003c/p\u003e\u003cp\u003eThere were two notable differences identified between the two studies, one in design and one in the emerging final outputs. First: the antiviral compounds were acyclovir for the Sullivan study and valacyclovir for the Engstrom study. Sullivan used acyclovir at a dose of 2000mg for 10 days giving a total dose of 20g. The valacyclovir dose used by Engstrom was two 500mg tablets three times a day for 7 days giving a total dose of 21g. However, the main observation of the pharmacokinetics of the two drugs is the difference in oral bioavailability of acyclovir. Valacyclovir is rapidly hydrolysed after oral administration to form acyclovir, resulting in an acyclovir bioavailability of 3 to 5 times that of oral acyclovir (Miserocci 2007 [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], Patel 1997 [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]). The plasma concentration of acyclovir following oral administration of valacyclovir is similar to that achieved with intravenous acyclovir (Wei 2021 [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]). This means that whilst the original doses seem similar (within 5% of each other) the resulting plasma concentration of antiviral will have been greater in the Engstrom trial.\u003c/p\u003e\u003cp\u003eBoth steroid compounds were prednisolone; indistinguishable placebo compounds were lactose. The prednisolone dose was 25mg twice daily for 10 days giving a total dose of 500mg (Sullivan) or 12 x 5mg tablets for the first 5 days and then reduced by 10mg per day over a total treatment time of 10 days giving a total dose of 450mg (Engstrom).\u003c/p\u003e\u003cp\u003eSecond: notwithstanding the difference in antiviral treatment one might reasonably have anticipated the patient experience on placebo and on steroid alone to be broadly indistinguishable: in fact in Sullivan\u0026rsquo;s study, 104 of 122 patients on placebo (85%) were recovered at 9 months, along with 122 of 127 patients on prednisolone alone (96%). In Engstrom\u0026rsquo;s study, after 12 months\u0026rsquo; observation, the respective rates were 133/206 (65%) and 160/210 (76%). So, across both treatment regimes, and even with a longer assessment period that might have permitted a greater opportunity for recovery, the progress achieved was significantly lower for Engstrom\u0026rsquo;s study (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001 on placebo, and also on prednisolone). Possible rationales for these observed differences include some previously unremarked distinction in genetic make-up, environmental differences, properties of the two different antivirals, or even in the application of the House-Brackmann instrument, though this measure is widely used because of its ease and consistency.\u003c/p\u003e\u003cp\u003eThe broad similarities in outcome between the two studies were nevertheless striking. Both studies demonstrated significant benefit in overall recovery for patients receiving prednisolone compared with those not (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001); and no benefit in either case from either antiviral compound (Sullivan SP\u0026thinsp;~\u0026thinsp;0.07, Engstrom SP\u0026thinsp;~\u0026thinsp;0.65). Drug interaction was insignificant in both studies.\u003c/p\u003e\u003cp\u003eThe two study databases were merged into a single spreadsheet and the combined dataset was then modelled for time to recovery.\u003c/p\u003e\u003cp\u003eThe visit schedule in both studies meant that a determination of recovery to the exact day was not possible, only that recovery occurred over some known interval (or not at all). The interval data do not in themselves render any difficulty with the estimation of quality of fit or of the associated model parameters; however, the highly aggregated data for both studies blurs any convincing individual best fit. Amongst the usual competitors (exponential, Weibull, Gompertz, lognormal) the exponential fit had a significantly larger deviance across all treatments (i.e. the worst-fitting model considered); there was little to choose between the other three potential models though the lognormal fit, possessing the smallest deviance (Akaike 1973 [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]) was marginally best across all treatments. Considered together with the very substantial advantage that application of this model permits an easy assessment of differences and their significance based on normal distribution theory, this was the model selected.\u003c/p\u003e\u003cp\u003eOnce established, the model was used to compare the distribution of time to recovery between the 4 treatment arms as well as direct comparison between those that received prednisolone and those that did not, and those that received antivirals against those that did not.\u003c/p\u003e\u003cp\u003eTime to recovery, rather than the achievement of recovery, was the primary focus of the analysis. Timelines illustrating recovery probability were then created from these probability models displaying likelihood of recovery at key time markers (30, 60, 90, 180, 270 and 360 days).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe merged dataset was made up of 1321 patients (829 from the Engstrom study, 492 from the Sullivan study) stratified by initial treatment allocation and displaying the time between presentation and the first assessment to have recovered according to the House-Brackman scoring system. Of those 1321, 298 (22.49%) were not observed to have recovered within the observation periods of the original studies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eProbability modelling generated the following Figures 1, 2 and 3 displaying the proportion of each treatment group that is expected to have recovered with reference to time since initial presentation and treatment.\u003c/p\u003e\n\u003cp\u003eFrom these figures was extracted the probability of recovery at certain arbitrary time points, 30, 60, 90, 180, 270 and 360 days respectively (see Table 1); and for each group quartile-recovery dates were also identified from the fitted model (see Table 2).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Table 1: Proportion recovered at notable prognostic time intervals by treatment allocation.\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 399px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRecovery Rate (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDay 30\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDay 60\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDay 90\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDay 180\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDay 270\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDay 360\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e35.2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e53.1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e63.5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e78.8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e85.7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e89.5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAO\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e26.6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e39.5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e47.7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e61.8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e69.5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e74.5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e35.2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e52.8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e63.1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e78.4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e85.3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e89.2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOO\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e27.6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e41.3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e50.0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e64.7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e72.5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e77.4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e30.7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e45.9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e55.2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e70.2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e77.7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e82.4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNot A\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e31.3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e46.8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e56.4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e71.5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e79.1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e83.6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e35.2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e52.9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e63.3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e78.6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e85.5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e89.4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNot P\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e27.1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e40.4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e48.9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e63.2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e71.0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e76.0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2: Duration in days for each quartile to recover depending on treatment allocation.\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 320px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eQuartiles (days)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eQ\u003csub\u003e0.25\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eQ\u003csub\u003e0.50\u003c/sub\u003e (median)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eQ\u003csub\u003e0.275\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e19\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e53\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e149\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAO\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e27\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e101\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e371\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e19\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e54\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e152\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOO\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e26\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e90\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e312\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e22\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e72\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e231\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNot A\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e22\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e69\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e215\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e19\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e54\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e150\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNot P\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e27\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e340\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eThe argument for antivirals\u003c/h2\u003e\u003cp\u003eWhilst the aetiology of Bell\u0026rsquo;s palsy remains elusive, one school of thought holds that herpes (Herpes simples virus type 1 and Herpes zoster virus are both cited as possible causative agents) viral reactivation in the geniculate ganglion of the facial nerve could be the cause via inflammation and nerve compression within the narrow fallopian canal (Loukas 2014 [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]). Following this, prescription of acyclovir was considered to combat viral load. Early studies supported the use of antivirals in combination with corticosteroids (Shahidullah 2011 [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]); and in 2014 the Bell\u0026rsquo;s Palsy Working Group of the Canadian Society of Otolaryngology published guidelines encouraging co-prescription of antiviral and corticosteroids for severe and complete cases of facial paralysis (de Almeida [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]). The American Academy of Otolaryngology similarly published guidelines suggesting co-prescription as an option as antivirals offered \u0026lsquo;small potential improvement in facial nerve function\u0026rsquo; (Baugh 2013 [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]). Several online sources of medical advice intended for healthcare professionals still suggest that prescribing antivirals such as acyclovir \u0026lsquo;\u003cem\u003emay be reasonable\u0026rsquo;\u003c/em\u003e (Grogan 2001 [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], Taylor 2021 [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]); yet more recent studies fail to find any benefit by their inclusion in treatment Marques Gomes 2024 [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]). However, with possible side effects of antivirals such as acyclovir including diarrhoea and vomiting and, in rare cases, hepatic disorders and renal impairment, it is important that antivirals are only prescribed if they will give therapeutic benefit (Joint Formulary Committee [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]).\u003c/p\u003e\u003cp\u003eThis study has formed and then statistically analysed a large database of patients from controlled trials looking at the efficacy of different treatment regimens for Bell\u0026rsquo;s palsy. This study focused on both absolute probability of recovery and median time to recovery. These are important factors as knowledge of prognosis depending on treatment will help dictate regimes chosen by patients.\u003c/p\u003e\u003cp\u003eTreatment with prednisolone gave a significant increase in overall recovery probability and reduced the median time to recovery. Antiviral therapy had no effect on likelihood of recovery or duration of disease. Combination therapy was no more effective than corticosteroid monotherapy across either metric.\u003c/p\u003e\u003cp\u003e\u003cb\u003eEfficacy of Antiviral therapy -\u003c/b\u003e There was no discernible difference in overall recovery probability or in median duration of disease between participants who received Antivirals and those who did not (A vs Not A SP\u0026thinsp;=\u0026thinsp;0.693) as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cb\u003eEfficacy of Corticosteroid therapy \u0026ndash;\u003c/b\u003e There is a significant increase in overall recovery probability when treated with prednisolone (P vs not P) for overall recovery probability SP\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Likewise, there is a significant reduction in median time to recovery for the patients who received prednisolone compared to those who received only antiviral or placebo treatments. Again a consideration of P vs Not P, but through a comparison of median time to recovery not overall recovery chance (SP\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) as demonstrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cb\u003eEfficacy of dual therapy -\u003c/b\u003e There was also no difference in either overall recovery probability or median time to recovery between the group given a combination of corticosteroid\u0026thinsp;+\u0026thinsp;antiviral and the group given corticosteroid\u0026thinsp;+\u0026thinsp;placebo This is AP vs OP. and is intended to highlight that there is no evidence of synergistic effect (SP 0.750) Shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e \u0026ndash; there is no divergence between treatment groups AP and OP.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eStrengths and limitations\u003c/h3\u003e\n\u003cp\u003eBoth studies were designed for maximum generalisability and used common and moderately inexpensive easily available treatment compounds. By merging the databases we have increased the potential for convincing argument. The methodology adopted for their analysis is conventional and well-known, and has yielded conclusive results.\u003c/p\u003e\u003cp\u003eThis meta-analysis has produced easy to understand timelines of predicted recovery probability which are intended to ease decision making for patients affected by Bell\u0026rsquo;s palsy.\u003c/p\u003e\u003cp\u003eAlthough the reasons are different and inherent in their design, both studies lack the intensive monitoring of individual patient progress during the early period between onset and 3 months (or possibly 4) that would illuminate the critical interval over which the majority of recoveries across all treatments and combinations is achieved. A future study whose focus was on disease duration rather than whether resolution occurs at all would need a greater frequency of assessments to provide a better estimation of disease duration.\u003c/p\u003e\u003cp\u003eThe patient demography in both studies was not distinguished in any important characteristic. The Scandinavian study extended over a longer time frame than the Scottish study allowing, in principle, a greater opportunity for recovery to occur. However, one might have anticipated broadly similar outcomes, even if only in the double-placebo (OO) and steroid-only (OP) groups. In fact there were surprising and significant differences.\u003c/p\u003e\u003cp\u003eWe have not adequately explained the differences in overall rates of recovery that have been referenced for the two studies. It may be that the higher bioavailability of the antiviral drug in the Engstrom study had a negative effect. Neurotoxicity has been reported with Acyclovir, though it is not well understood [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. We remain confident that the similarities in design, delivery and outcome for these two studies offer more encouragement for the principle of merging than the differences offer against it.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe have identified an important practical issue (patients\u0026rsquo; concerns about disease duration) and the principle of its resolution. The data have provided meaningful and easily conveyed estimates that can usefully be shared with patients concerned about their chances of recovery and the time that that recovery might take, which enable an informed choice of treatment pathway. We have also shown that antiviral adjunct therapy has no effect on duration of disease.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval for analysis of secondary data was granted by the University of St Andrews ethics committee. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from participants before inclusion in the original studies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent for publication of results was obtained from participants before inclusion in the original studies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWilliam Kingston received funding from the University of St Andrews to complete this research.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data underlying this study are available on request to the corresponding author, Professor Fergus Daly - [email protected].\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHolland NJ, Bernstein JM. Bell\u0026apos;s palsy. BMJ Clin Evid [Internet]. 2014 [cited; 2014.\u003c/li\u003e\n\u003cli\u003eRonthal M. Bell\u0026apos;s Palsy: Treatment and Prognosis in Adults 2023 [Available from: https://www.uptodate.com/contents/bells-palsy-treatment-and-prognosis-in-adults?csi=15745a5f-3f77-4b61-b638-e82adf62c581\u0026amp;source=contentShare .\u003c/li\u003e\n\u003cli\u003eDe Almeida JR, Guyatt GH, Sud S, Dorion J, Hill MD, Kolber MR, et al. Management of Bell palsy: clinical practice guideline. Canadian Medical Association Journal [Internet]. 2014 [cited; 186(12):917-22. Available from: 10.1503/cmaj.131801.\u003c/li\u003e\n\u003cli\u003eDe Almeida JR, Al Khabori M, Guyatt GH, Witterick IJ, Lin VYW, Nedzelski JM, et al. Combined Corticosteroid and Antiviral Treatment for Bell Palsy. JAMA [Internet]. 2009 [cited; 302(9):985. Available from: 10.1001/jama.2009.1243.\u003c/li\u003e\n\u003cli\u003eKim SJ, Lee HY. Acute Peripheral Facial Palsy: Recent Guidelines and a Systematic Review of the Literature. Journal of Korean Medical Science [Internet]. 2020 [cited; 35(30). Available from: 10.3346/jkms.2020.35.e245.\u003c/li\u003e\n\u003cli\u003eNHS. Bell\u0026apos;s Palsy https://www.nhs.uk/conditions/bells-palsy/ 2023 [Available from: https://www.nhs.uk/conditions/bells-palsy/\u003c/li\u003e\n\u003cli\u003eMedicalNewsToday. What are the Signs of Bell\u0026apos;s Palsy Recovery 2023 [Available from: https://www.medicalnewstoday.com/articles/bells-palsy-recovery-signs#how-long-does-recovery-take.\u003c/li\u003e\n\u003cli\u003eAmericanAcademyofFamilyPhysicians. Bell\u0026apos;s Palsy 2022 [Available from: https://familydoctor.org/condition/bells-palsy/.\u003c/li\u003e\n\u003cli\u003eSullivan FM, Swan IRC, Donnan PT, Morrison JM, Smith BH, McKinstry B, et al. Early Treatment with Prednisolone or Acyclovir in Bell\u0026apos;s Palsy. New England Journal of Medicine [Internet]. 2007 [cited; 357(16):1598-607. Available from: 10.1056/nejmoa072006.\u003c/li\u003e\n\u003cli\u003eEngstr\u0026Atilde;\u0026para;m M, Berg T, Stjernquist-Desatnik A, Axelsson S, Pitk\u0026Atilde;\u0026curren;ranta A, Hultcrantz M, et al. Prednisolone and valaciclovir in Bell\u0026apos;s palsy: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet Neurol [Internet]. 2008 [cited; 7(11):993-1000. Available from: 10.1016/s1474-4422(08)70221-7.\u003c/li\u003e\n\u003cli\u003eHouse JW, Brackmann DE. Facial Nerve Grading System. Otolaryngology\u0026acirc;\u0026euro;\u0026ldquo;Head and Neck Surgery [Internet]. 1985 [cited; 93(2):146-7. Available from: 10.1177/019459988509300202.\u003c/li\u003e\n\u003cli\u003eMiserocchi E, Modorati G, Galli L, Rama P. Efficacy of valacyclovir vs acyclovir for the prevention of recurrent herpes simplex virus eye disease: a pilot study. Am J Ophthalmol [Internet]. 2007 [cited; 144(4):547-51. Available from: 10.1016/j.ajo.2007.06.001.\u003c/li\u003e\n\u003cli\u003ePatel R. Valaciclovir: development, clinical utility and potential. Expert Opin Investig Drugs [Internet]. 1997 [cited; 6(2):173-89. Available from: 10.1517/13543784.6.2.173.\u003c/li\u003e\n\u003cli\u003eWei Y-P, Yao L-Y, Wu Y-Y, Liu X, Peng L-H, Tian Y-L, et al. Critical Review of Synthesis, Toxicology and Detection of Acyclovir. Molecules [Internet]. 2021 [cited; 26(21):6566. Available from: 10.3390/molecules26216566.\u003c/li\u003e\n\u003cli\u003eAkaike, H. (1973), Information theory and an extension of the maximum likelihood principle, in Petrov, B. N.; Cs\u0026aacute;ki, F. (eds.), 2nd International Symposium on Information Theory, Tsahkadsor, Armenia, USSR, September 2-8, 1971, Budapest: Akad\u0026eacute;miai Kiad\u0026oacute;, pp. 267\u0026ndash;281. Republished in Kotz, S.; Johnson, N. L., eds. (1992), Breakthroughs in Statistics, vol. I, Springer-Verlag, pp. 610\u0026ndash;624.\u003c/li\u003e\n\u003cli\u003eLoukas M. The neurologist\u0026acirc;\u0026euro;\u0026trade;s dilemma: A comprehensive clinical review of Bell\u0026acirc;\u0026euro;\u0026trade;s palsy, with emphasis on current management trends. Medical Science Monitor [Internet]. 2014 [cited; 20:83-90. Available from: 10.12659/msm.889876.\u003c/li\u003e\n\u003cli\u003eShahidullah M, Haque A, Islam MR, Rizvi AN, Sultana N, Mia BA, et al. Comparative study between combination of famciclovir and prednisolone with prednisolone alone in acute Bell\u0026apos;s palsy. Mymensingh Med J [Internet]. 2011 [cited; 20(4):605-13.\u003c/li\u003e\n\u003cli\u003eBaugh RF, Basura GJ, Ishii LE, Schwartz SR, Drumheller CM, Burkholder R, et al. Clinical Practice Guideline: Bell\u0026apos;s Palsy Executive Summary. Otolaryngology\u0026acirc;\u0026euro;\u0026ldquo;Head and Neck Surgery [Internet]. 2013 [cited; 149(5):656-63. Available from: 10.1177/0194599813506835.\u003c/li\u003e\n\u003cli\u003eGrogan PM, Gronseth GS. Practice parameter: Steroids, acyclovir, and surgery for Bell\u0026acirc;\u0026euro;\u0026trade;s palsy (an evidence-based review) [RETIRED]. Neurology [Internet]. 2001 [cited; 56(7):830-6. Available from: doi:10.1212/WNL.56.7.830.\u003c/li\u003e\n\u003cli\u003eTaylor DC. Bell Palsy Treatment \u0026amp; Management: MedScape. 2021 [Available from: https://emedicine.medscape.com/article/1146903-treatment#d10.\u003c/li\u003e\n\u003cli\u003eMarques Gomes P, Cunha Cabral, D., Alves Carc\u0026Igrave;\u0026sect;a\u0026Igrave;\u0026fnof;o A., Ferreira Pene\u0026Igrave;\u0026sbquo;da J., Duarte, D., \u0026amp; Azevedo, P. Prognostic Factors for Recovery in Bell\u0026acirc;\u0026euro;\u0026trade;s Palsy. . ENT Updates, 14(2), 32\u0026acirc;\u0026euro;\u0026ldquo;36 [Internet]. 2024 [cited. Available from: https://doi.org/10.5152/entupdates.2024.24363.\u003c/li\u003e\n\u003cli\u003eJoint Formulary Committee. British National Formulary (online) London: BMJ and Pharmaceutical Press \u0026lt;http://www.medicinescomplete.com\u0026gt; [Accessed on [02/10/2024]].\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7355290/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7355290/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eIdiopathic peripheral facial paralysis (Bell\u0026rsquo;s palsy) is commonly treated with corticosteroids and sometimes with antiviral therapy in combination. The benefits of corticosteroids for long term complete recovery are well established but the effect of treatment and different treatment combinations on duration of disease are not well discussed in the literature and so is the focus of this investigation.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eTwo randomised controlled studies that were broadly similar in their objectives (being primarily the chances of recovery by end of study), design (different treatment combinations that were very similar in both studies), instruments (measurement of severity), delivery (a visit regime over approximately one year) and in their consideration of outputs (proportion recovered) additionally provided sufficient data for a secondary investigation of duration of symptoms. Probability models for duration were compared and the best-fitting model was selected.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA significant reduction in median time to recovery after treatment with prednisolone was identified, compared with treatment without prednisolone (54 days vs. 95 days: significance probability SP\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Antivirals had no observable effect on time to recovery whether considered alone (101 days vs. 90 days; SP\u0026thinsp;=\u0026thinsp;0.571) or in combination with prednisolone (53 days vs. 54 days; SP\u0026thinsp;=\u0026thinsp;0.750). The fitted model was used to provide estimated quantiles and estimates of recovery rates at key intervals.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThese results amplify those previously identified when exploring achievement of final recovery but provide an important additional information about the rate of recovery to patients concerned about their immediate prognosis, and to aid patients and practitioners in their discussion of treatment options.\u003c/p\u003e","manuscriptTitle":"A meta-analysis and modelling of the duration of symptoms in Bell’s palsy in the Scottish and Scandinavian trials","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-24 15:49:47","doi":"10.21203/rs.3.rs-7355290/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-10-08T10:21:59+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-03T06:58:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"287159778667381126191353266148238471512","date":"2025-09-29T12:47:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"9496845829628055599467543110892475733","date":"2025-09-25T06:01:12+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-24T10:46:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"10335610714868231375105968937285164290","date":"2025-09-23T07:31:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"332120567129216495210941607523123640605","date":"2025-09-23T04:47:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"339262815261482834814322809837439503402","date":"2025-09-18T05:35:15+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-16T03:10:01+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-08-20T17:44:21+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-17T23:50:39+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-17T23:49:23+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2025-08-12T11:36:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d333aa8d-b20e-4e6c-b257-b676a43bc543","owner":[],"postedDate":"September 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-09-24T15:49:47+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-24 15:49:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7355290","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7355290","identity":"rs-7355290","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}