Botulinum toxin in peripheral facial paralysis: systematic review and rehabilitation perspectives

Abstract

BACKGROUND

Peripheral facial paralysis (PFP) causes both static and dynamic facial dysfunctions, leading to synkinesis, hypertonia, and aesthetic asymmetry that significantly affect quality of life. Botulinum toxin type A (BTX-A) has become an effective adjunct in rehabilitation, improving facial balance and function. However, there is no consensus regarding optimal injection patterns, dosage, or the therapeutic role of contralateral treatment.

METHODS

A systematic review of the literature was conducted in accordance with the PRISMA 2020 guidelines. The MEDLINE (PubMed) database was searched for studies published between January 2013 and January 2024 using the terms “Facial Paralysis” AND “Botulinum Toxin.” Randomized controlled trials, cohort, and observational studies in English or Spanish analyzing BTX-A treatment in peripheral facial paralysis were included. Data on toxin formulation, injection site, dosage, and outcomes were extracted and qualitatively analyzed.

RESULTS

Thirteen studies met the inclusion criteria, encompassing 1821 patients. OnabotulinumtoxinA was the most frequently used formulation. Injections on the affected side were mainly indicated for synkinesis, while contralateral injections aimed to reduce hypertonia and restore facial symmetry. Reported doses ranged from 0.6 to 7.5 U per point. Across studies, BTX-A improved facial symmetry, reduced synkinesis, and enhanced quality of life, with only mild and transient adverse effects.

CONCLUSIONS

Botulinum toxin is a safe and effective therapeutic tool within the multidisciplinary rehabilitation of peripheral facial paralysis. Despite consistent clinical benefits, heterogeneity in dosing and injection protocols persists. Future randomized studies combining BTX-A therapy with structured neuromuscular rehabilitation are needed to establish standardized evidence-based guidelines.

Introduction

Background

Peripheral facial palsy (PFP), resulting from dysfunction of the seventh cranial nerve, is among the most frequent mononeuropathies of the cranial nerves. Regardless of etiology, it leads to a unilateral paralysis of facial muscles that compromises both static and dynamic expressions, often resulting in significant aesthetic disfigurement, communication difficulties, and impaired emotional expression. These physical alterations profoundly affect quality of life, producing psychological consequences such as social withdrawal, anxiety, and reduced self-esteem.^1-3

The incidence of idiopathic or Bell’s palsy is estimated at 20-30 cases per 100,000 individuals annually, but secondary forms due to trauma, infection, or iatrogenic causes remain clinically relevant.^{4, 5}

Although most patients recover partially within weeks, approximately 15-30% develop long-term sequelae characterized by residual weakness, facial asymmetry, hypertonia, or involuntary synkinetic movements.³ These sequelae generate a persistent physical and emotional burden, particularly because facial movement plays a crucial role in nonverbal communication and social interaction.⁴

Patients frequently report distress, altered social relationships, and a reduced sense of identity, underscoring the necessity for multidisciplinary management that combines medical, surgical, and rehabilitative approaches.^{5, 6}

Functional and clinical sequelae

Facial nerve injury triggers a complex cascade of regenerative and maladaptive processes. When nerve recovery is incomplete, abnormal reinnervation can occur, resulting in unwanted cross-activation between motor units. Although the exact pathogenesis of facial palsy sequelae remains incompletely understood, aberrant axonal regeneration, collateral sprouting, and synaptic reorganization at the facial nucleus are considered central mechanisms responsible for synkinesis, spasms, and hypertonia.^{2, 3, 7}

Synkinesis refers to the involuntary co-contraction of muscles during voluntary facial movement, most often affecting muscle groups that normally act synchronously, such as the zygomaticus major and depressor anguli oris, or the platysma.^{2, 7} This abnormal coupling alters facial symmetry, limits expressive mobility, and can extend to the contralateral side either through maladaptive cortical compensation or bilateral hypertonic response. The chronic maintenance of muscle contraction leads to structural changes, discomfort, and fatigue, further perpetuating functional impairment.^{5, 8}

Facial sequelae can involve multiple dynamic and static components: resting asymmetry, lagophthalmos, oro-ocular synkinesis, oral commissure deviation, and platysmal contracture. Over time, these complications evolve into a distinct clinical entity requiring targeted rehabilitation and often pharmacologic intervention.^{3, 4} The therapeutic objective is twofold: to restore function and expression on the affected side while achieving global facial symmetry, thereby improving both functional outcomes and psychosocial well-being.^{2, 3, 7}

Pathophysiological rationale for botulinum toxin in rehabilitation

The therapeutic use of botulinum toxin type A (BTX-A) in facial palsy rehabilitation is based on its precise and reversible chemodenervation effect at the neuromuscular junction. BTX-A inhibits the release of acetylcholine by cleaving the SNAP-25 protein in presynaptic vesicles, thereby blocking synaptic transmission and inducing temporary muscle relaxation.^{9, 10} This mechanism not only reduces hyperactivity and involuntary contraction but also allows for rebalancing of facial dynamics by selectively weakening overactive muscles, both on the affected and the contralateral sides.^{2, 11}

The role of BTX-A extends beyond simple muscular paralysis. Several studies have suggested that it may modulate aberrant motor reinnervation and central plasticity. Neurophysiological data demonstrate that BTX-A injections can reduce abnormal co-activation patterns, allowing for more efficient voluntary control of target muscles.^{4, 8} Additionally, BTX-A may induce favorable cortical reorganization, enabling improved functional recovery through the reestablishment of appropriate motor pathways when combined with neuromuscular retraining (NMR) and mirror therapy.^{8, 9}

Clinically, BTX-A is applied to alleviate synkinesis, hypertonia, and facial asymmetry. It can be used on the paralyzed side to diminish unwanted co-contractions and on the contralateral side to correct compensatory hyperactivity and restore balance.^{5, 11} Since its first documented use in treating blepharospasm in 1980, its indications have expanded to the rehabilitation of facial nerve palsy, initially for synkinesis control and later for symmetry optimization through contralateral injections.^{2, 12, 13}

Recent studies have also highlighted the neurophysiological safety and dose-dependent efficacy of BTX-A in facial applications. Alimohammadi et al. demonstrated a linear correlation between dosage and muscle response in the glabellar complex, confirming predictable outcomes without neurotoxicity.⁹ Comparative studies of commercially available neuromodulators (onabotulinumtoxin A, abobotulinumtoxin A, incobotulinumtoxin A) have shown similar efficacy profiles in reducing synkinesis and improving functional symmetry.¹⁰ Moreover, BTX-A appears to positively influence motor relearning by reducing involuntary antagonist activation, thus facilitating correct movement patterns during physical therapy.^{5, 8}

In summary, BTX-A’s multifactorial effects – chemical denervation, cortical modulation, and facilitation of neuromuscular reeducation – support its integration into modern rehabilitation paradigms for PFP. Its selective and reversible action enables individualized treatment strategies based on patient-specific muscular involvement and functional goals.^{6, 11}

Rationale for the review

Despite its widespread clinical use, there remains no universally accepted guideline for BTX-A therapy in facial palsy. Considerable heterogeneity exists in injection protocols, muscle targets, dosage per point, and timing of intervention, which complicates the interpretation and comparison of published outcomes.^{2, 11-13} While some practitioners advocate early contralateral injections to promote balance, others prefer delayed treatment once synkinesis develops, reflecting ongoing debate about optimal timing.^{5, 6}

Furthermore, outcome measures vary widely across studies, ranging from clinician-rated scales such as the House-Brackmann (HB) and Sunnybrook Facial Grading System (SFGS) to patient-reported instruments like the Synkinesis Assessment Questionnaire (SAQ) and Facial Clinimetric Evaluation (FaCE). This diversity underscores the need for critical evaluation and synthesis of current evidence to clarify therapeutic efficacy and define standardized treatment recommendations.^{5, 8}

Over the last decade, a growing body of literature has investigated the effects of BTX-A on facial function, quality of life, and rehabilitation outcomes. However, most studies are limited by small sample sizes, short follow-up periods, or nonuniform methodologies. Systematic analyses integrating both clinical and functional outcomes are scarce, particularly regarding long-term efficacy and the combination of BTX-A with physiotherapeutic approaches.^{5, 6, 8} Given this context, a comprehensive review is essential to assess the evolution of evidence, summarize current practices, and identify knowledge gaps. The present study therefore systematically examines research published between January 2013 and January 2024, focusing on the patterns of botulinum toxin application, therapeutic outcomes, and safety in both acute and chronic stages of peripheral facial palsy.

Objective

The objective of this review is to synthesize and critically analyze the existing scientific evidence regarding the use of BTX-A in the rehabilitation of PFP. Specifically, the review aims to describe treatment patterns, dosing strategies, clinical outcomes, and the underlying pathophysiological rationale supporting its use in both the paralyzed and contralateral facial musculature. Through this analysis, the study seeks to provide an updated, evidence-based perspective that supports the integration of BTX-A as a core component of multidisciplinary facial rehabilitation programs.

Methods

Study design

This study was conducted as a systematic review of the literature examining the role of BTX-A in the management of PFP. The review was designed and reported in accordance with the PRISMA 2020 statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) to ensure transparency and reproducibility in the identification, selection, and synthesis of relevant studies.

The methodological process included a predefined search strategy, explicit eligibility criteria, structured study selection, and systematic data extraction. Due to the heterogeneity of study designs, outcome measures, and treatment protocols reported in the literature, the results were synthesized through qualitative narrative analysis rather than quantitative meta-analysis.

The review protocol was not prospectively registered in a public database such as PROSPERO, which represents a methodological limitation. However, the study adhered to established principles of systematic review methodology to ensure transparency and methodological rigor in the analysis of available evidence.

Search strategy

An electronic bibliographic search was conducted using the MEDLINE (PubMed) database to identify original research articles published between January 2013 and January 2024. The search was limited to studies published in English or Spanish. The main search terms and Boolean operators applied were: (“Facial Paralysis” OR “Facial Palsy”) AND (“Botulinum Toxin” OR “Botulinum Toxin Type A” OR “BTX-A”).

Search filters were restricted to human studies. Additional manual searches were performed by examining the reference lists of the retrieved articles to identify relevant studies not captured by the electronic search. Titles and abstracts were screened for relevance, and potentially eligible full-text articles were obtained for detailed evaluation.

To ensure completeness, the search strategy was designed to capture studies evaluating both acute and chronic stages of facial paralysis treated with botulinum toxin, as well as interventions aimed at improving facial symmetry, synkinesis, and muscle tone regulation.

Eligibility criteria

Eligibility criteria were established a priori to include studies providing quantitative or qualitative data on the use of botulinum toxin for PFP. Studies were eligible if they met the following conditions:

• study design: randomized controlled trials (RCTs), prospective or retrospective cohort studies, and comparative observational studies;

• population: adult or pediatric patients diagnosed with peripheral facial palsy of any etiology (idiopathic, traumatic, infectious, or postsurgical);

• intervention: infiltration with BTX-A (onabotulinum, incobotulinum, or abobotulinum), administered for facial symmetry, synkinesis reduction, or hypertonia management;

• outcome measures: functional recovery, facial symmetry, reduction of synkinesis, or patient-reported quality of life outcomes, evaluated through validated tools such as the SAQ, SFGS, HB, or FaCE;

• publication language: English or Spanish;

• availability: Full-text accessible through institutional or open-access sources.

Exclusion criteria

The following criteria were applied to exclude non-eligible studies:

• publications written in languages other than English or Spanish;

• review articles, meta-analyses, editorials, or expert commentaries;

• experimental studies in animals or preclinical in vitro research;

• studies investigating botulinum toxin applications unrelated to facial paralysis (e.g., dystonia, hyperhidrosis, migraine, or spasticity);

• articles evaluating alternative therapeutic approaches for facial palsy (e.g., surgical reanimation, nerve grafting, physical therapy alone);

• studies not available in full text or lacking sufficient methodological details.

Study selection

The selection process was performed in two stages.

• initial screening: titles and abstracts were independently reviewed by two investigators to identify potentially relevant studies. Any discrepancies regarding inclusion were resolved by discussion and consensus;

• full-text assessment: full-text versions of all potentially eligible articles were reviewed to confirm compliance with the inclusion and exclusion criteria.

A PRISMA flow diagram was constructed to summarize the selection process. From an initial yield of 196 records, 41 duplicates were excluded. After title and abstract screening, 23 studies were retained for full-text review. Ultimately, 13 studies fulfilled all inclusion criteria and were incorporated into the final synthesis.

Data extraction and synthesis

Data from the included studies were systematically extracted using a structured template developed by the authors. Extracted information included:

• study identification: author, year of publication, country, and design;

• population characteristics: sample size, sex distribution, age range, and etiology of paralysis;

• intervention details: type of botulinum toxin, total dose, injection pattern, laterality (paralyzed or contralateral side), and treatment phase (acute or chronic);

• outcome measures: type of functional or patient-reported assessment tool used and reported changes in symmetry, synkinesis, and quality of life;

• safety data: presence and type of adverse effects, if reported.

No quantitative meta-analysis was attempted because of heterogeneity in study design, outcome measures, and dosing protocols. Instead, results were synthesized qualitatively and described narratively to identify recurring patterns, treatment trends, and outcome consistency across studies.

Quality assessment and risk of bias

Although the review was primarily descriptive, the methodological quality of each included study was critically appraised. For randomized controlled trials, the Cochrane Risk of Bias tool (RoB 2) was applied, and for observational studies, the Newcastle-Ottawa Scale (NOS) was used to assess the adequacy of selection, comparability, and outcome evaluation. All studies were independently evaluated by the author, who applied both tools following the respective published guidelines. Studies achieving a NOS score of ≥7 were classified as high quality, while those scoring ≤6 were considered of moderate or low quality. The risk of publication bias was qualitatively discussed considering the heterogeneity of study designs and reported outcomes. The results of the methodological quality assessment are summarized in Table I.^{12, 14-25}

Table I. —Quality assessment and risk of bias tool of included studies.^{12, 14-25}.

Study	Study design	Tool used	Score/risk	Quality level
Cecini et al.14	Prospective observational	NOS	7	High
Choi et al.12	Prospective observational	NOS	6	Moderate
Kim et al.15	Prospective observational	NOS	6	Moderate
Dall’Angelo et al.16	Retrospective observational	NOS	6	Moderate
Risoud et al.17	Retrospective observational	NOS	6	Moderate
Wei et al.18	Retrospective observational	NOS	6	Moderate
Akulov et al.19	Randomized controlled trial	RoB 2	Some concerns	Some concerns
Neville et al.20	Prospective observational	NOS	6	Moderate
Patel et al.21	Comparative prospective	NOS	9	High
Shinn et al.22	Prospective observational	NOS	8	High
Kanerva et al.23	Retrospective observational	NOS	6	Moderate
Díaz-Aristizabal et al.24	Prospective cohort	NOS	6	Moderate
Steinhäuser et al.25	Retrospective observational	NOS	8	High

NOS: Newcastle-Ottawa Scale; RoB 2: Cochrane Risk of Bias tool for randomized trials.

As this study involved a systematic review of published literature, no human participants or personal data were directly involved. Therefore, ethical approval was not required. All data were obtained from previously published sources available in the public domain.

Summary

In summary, this systematic review was conducted following PRISMA 2020 recommendations, covering studies published from January 2013 to January 2024. Thirteen original studies meeting the inclusion criteria were identified and analyzed. The methodological approach ensured a transparent, replicable, and comprehensive synthesis of evidence regarding the use of botulinum toxin type A in both acute and chronic stages of peripheral facial palsy.

Results

Study selection and characteristics

The electronic search yielded a total of 196 records in MEDLINE. After removing duplicates and applying the predefined inclusion and exclusion criteria, 13 studies met the eligibility criteria and were included for qualitative synthesis and critical analysis. These studies focused on the use of botulinum toxin type A in the treatment of patients with peripheral facial palsy, addressing both acute and chronic phases of the condition (Figure 1).

Figure 1.

—Flow diagram illustrating the study selection process according to PRISMA guidelines.

The selected literature comprised four prospective observational studies, one prospective comparative study, one prospective observational cohort, one randomized prospective study, and five retrospective observational studies, including a total of 1821 patients. The sample size of the included studies ranged from 28 to 1220 participants. A summary of the main characteristics of the studies is presented in Table II.^{12, 14-25}

Table II. —Characteristics of included studies. Summary of study design, publication year, and number of patients analyzed in each included study.^{12, 14-25}.

Study	Year	Study type	N.
Cecini et al.14	2013	Prospective observational	29
Choi et al.12	2013	Prospective observational	42
Kim et al.15	2013	Prospective observational	18
Dall’Angelo et al.16	2014	Retrospective observational	45
Risoud et al.17	2015	Retrospective observational	30
Wei et al.18	2016	Retrospective observational	42
Akulov et al.19	2017	Randomized controlled	76
Neville et al.20	2017	Prospective observational	51
Patel et al.21	2018	Comparative prospective	23
Shinn et al.22	2019	Prospective observational	99
Kanerva et al.23	2021	Retrospective observational	126
Díaz-Aristizabal et al.24	2021	Prospective cohort	20
Steinhäuser et al.25	2022	Retrospective observational	1220

Methodological quality and risk of bias

The methodological quality of the included studies was evaluated using the RoB 2 tool for randomized controlled trials and the NOS for observational studies.

Among the thirteen studies included in this review, one randomized controlled trial¹⁹ was evaluated using RoB 2 and was classified as presenting some concerns regarding risk of bias.

The remaining twelve observational studies were assessed using the Newcastle-Ottawa Scale. NOS scores ranged from 6 to 9 points, indicating moderate to high methodological quality. Four studies^{14, 21, 22, 25} achieved high-quality ratings, with scores between 7 and 9 points, reflecting robust study design and appropriate outcome assessment.

The remaining studies obtained moderate-quality scores, mainly due to limitations related to comparability between study groups, retrospective study design, or incomplete reporting of follow-up procedures.

Overall, although methodological heterogeneity was observed among the included studies, the overall quality of the available evidence was considered moderate to high, supporting the reliability of the qualitative synthesis presented in this review.

Type of botulinum toxin and treatment phase

Across the included studies, the therapeutic approach was primarily based on chemodenervation using botulinum toxin type A. Ten studies used onabotulinum toxin A (OnaBoNT-A), one used incobotulinum toxin A (IncoBTX-A), one applied both formulations, and one did not specify the type of toxin used.

Most studies targeted patients in the sequelae phase of PFP, characterized by the presence of synkinesis, hypertonia, or residual facial asymmetry. However, one study investigated the use of contralateral injections in the early or subacute stage following acute facial paralysis to improve facial symmetry and prevent long-term compensatory asymmetry.¹⁵

Assessment tools for functional and aesthetic outcomes varied among studies. The SAQ was the most frequently used scale, followed by the SFGS, FaCE HB scale, and Facial Disability Index (FDI) in selected reports. The inclusion of both clinician-rated and patient-reported measures allowed for a comprehensive evaluation of treatment response across studies. The type of toxin, timing of intervention, and assessment tools used in each study are summarized in Table III.^{12, 14-25}

Table III. —Type of botulinum toxin, clinical scales employed, stage of facial paralysis and specific therapeutic indications for botulinum toxin injection.^{12, 14-25}.

Study	Toxin type	Clinical scale	Phase	Indication
Cecini et al.14	OnaBoNT-A	SFGS	Chronic	Synkinesis
Choi et al.12	OnaBoNT-A	SFGS + Custom QoL scale	Chronic	Synkinesis + contralateral hypertonia
Kim et al.15	OnaBoNT-A	HB + Custom	Acute	Symmetry
Dall’Angelo et al.16	OnaBoNT-A	SFGS	Chronic	Synkinesis
Risoud et al.17	OnaBoNT-A	Unspecified	Chronic	Synkinesis, hypertonia
Wei et al.18	IncoBTX-A	SAQ	Chronic	Synkinesis
Akulov et al.19	OnaBoNT-A	SFGS, HB, FDI	Acute + Chronic	Synkinesis, symmetry, hypertonia
Neville et al.20	OnaBoNT-A	SAQ	Chronic	Synkinesis
Patel et al.21	OnaBoNT-A	SAQ	Chronic	Synkinesis
Shinn et al.22	OnaBoNT-A	SAQ	Chronic	Synkinesis, symmetry
Kanerva et al.23	OnaBoNT-A	Unspecified	Chronic	Synkinesis
Díaz-Aristizabal et al.24	OnaBoNT-A / IncoBTX-A	SAQ, SFGS, FaCE	Chronic	Synkinesis, hypertonia
Steinhäuser et al.25	Unspecified	FaCE, FDI	Acute + Chronic	Unspecified

OnaBoNT-A: onabotulinumtoxinA; IncoBTX-A: Incobotulinum toxin type A; HB: House–Brackmann Scale; SFGS: Sunnybrook Facial Grading System; SAQ: Synkinesis Assessment Questionnaire; FDI: Facial Disability Index; FaCE: Facial Clinimetric Evaluation.

Injection sites and dosing parameters

Injection protocols varied considerably among studies, reflecting differences in clinical presentation, muscle involvement, and practitioner experience. In total, ten studies specified the dosage per injection point on the affected side, with reported doses ranging from 0.6 to 7.5 U per point, most frequently 2.5 units (U) per point. For the non-paralyzed side, three of seven studies that performed contralateral infiltrations reported doses between 1.5 and 5 U per point.

The injected musculature was specified in eight studies. Infiltration was performed primarily in muscles affected by synkinetic movements on the paralyzed side, while some studies also included the non-paralyzed side to optimize facial symmetry.

The most frequently injected muscles on the paralyzed side were frontalis, corrugator supercilii, orbicularis oculi, zygomaticus major, and platysma, followed by levator labii superioris, levator alae nasi, orbicularis oris, mentalis, and depressor anguli oris.

Three studies specifically targeted buccinator synkinesis, often in combination with other perioral muscles,^{18, 21} while one study treated isolated platysma synkinesis.¹⁶

In cases where contralateral infiltration was performed, the indication was hypertonia or marked asymmetry. On the non-paralyzed side, the most commonly injected muscles were frontalis, corrugator, and depressor anguli oris, with additional injections in orbicularis oculi, zygomaticus, levator labii superioris, levator alae nasi, risorius, mentalis, orbicularis oris, and platysma.^{12, 15, 17}

The total dose per session ranged widely depending on clinical presentation, from 7.5 U to 100 U in smaller series^24, and up to 40-60 U in larger cohorts.^{17, 22} Shinn et al. reported mean doses of 2-3 U per facial muscle and 9-10 U for the platysma, with dosage adjustments during subsequent sessions until a steady-state response was achieved after approximately three treatment cycles.²²

The muscles targeted, number of injection points, and doses per muscle are detailed in Table IV.^{12, 14-25}

Table IV. —Injection sites and average doses for affected and healthy sides. Description of target muscles and mean botulinum toxin doses reported in the included studies for the paralyzed and contralateral sides.^{12, 14-25}.

Study	Affected side (targets and doses)	Healthy side (targets and doses)
Cecini et al.14	2-2.5 U/point (unspecified muscles)	None
Choi et al.12	1.5-2.5 U/point in corrugator, orbicularis oculi, zygomaticus	2.5-5 U/point frontal, DAO, corrugator
Kim et al.15	None	2.5-3 U/point frontal, corrugator, zygomaticus
Dall’Angelo et al.16	2.5 U/point, platysma 2-7 U/point	None
Risoud et al.17	1.5-2.5 U/point	1.5-2.5 U/point multiple facial muscles
Wei et al.18	1-1.5 U in synkinesis	2-4 U/point total 40-50 U
Akulov et al.19	0.6-2.5 U/point (buccinator)	None
Neville et al.20	0.5-5 U/point (unspecified muscles)	None
Patel et al.21	2.5 U (buccinator)	None
Shinn et al.22	2-3 U/point (platysma 9-10 U)	2-3 U/point frontal, corrugator, DAO
Kanerva et al.23	1.25-5 U/point (buccinator)	Unspecified
Díaz-Aristizabal et al.24	1-5 U/point multiple muscles	1-5 U/point frontal, zygomaticus
Steinhäuser et al.25	41 patients unspecified	132 patients unspecified

DAO: depressor anguli oris; U: units.

Laterality of injection

Of the 13 studies analyzed, 12 performed injections on the paralyzed side, whereas seven studies also included the non-paralyzed side to enhance symmetry. One study applied BTX-A exclusively to the non-paralyzed side in the acute phase following Bell’s palsy.¹⁵

Treatment of both sides was justified by the observation that compensatory hyperactivity of the healthy side contributes to resting asymmetry and dynamic imbalance. Contralateral weakening, therefore, improves facial harmony while facilitating rehabilitation of the affected muscles.

Functional and clinical outcomes

All included studies reported improvements in facial symmetry, reduction of synkinesis, and better quality of life after BTX-A treatment. Quantitative outcomes were documented using validated scales.

In the prospective cohort by Díaz-Aristizábal et al., SFGS scores improved significantly from 64.8 to 69.9 (P=0.004), while FaCE total and social subscales increased from 52.4 to 64.5 and 61.1 to 78.4, respectively (P<0.001). The SAQ score decreased from 46.2 to 37.6 (P=0.001), reflecting a reduction in synkinesis severity.²⁴

Similarly, Neville et al. demonstrated a significant reduction in SAQ scores in 51 patients after BTX-A injection, with mean pre- and post-treatment scores of 26.6±7.2 and 17.9±5.6, respectively (P<0.05). The effect remained significant after three treatment cycles, confirming the sustained efficacy of BTX-A.²⁰

In the large prospective cohort by Shinn et al. (N.=99), the mean total SAQ score improved by 14.2 points (P<0.001). The most responsive domains were oculo-oral and oro-ocular synkinesis, both improving significantly (P<0.001). Younger patients, females, and those receiving higher total doses exhibited greater improvements.²²

Studies focused on specific muscle groups showed comparable findings. Wei et al. and Patel et al., both analyzing buccinator synkinesis, demonstrated objective improvements in symmetry and reduction of involuntary contractions, with significant SAQ score decreases and no major complications.^{18, 21} Dall’Angelo et al. reported consistent improvement in cervical synkinesis after platysma injections, leading to enhanced lower-face movement and aesthetic balance.¹⁶

In patients treated after neurosurgical injury, Akulov et al. found that IncoBTX-A significantly improved symmetry, reduced hypertonia, and restored social confidence without relevant adverse effects.¹⁹ Kanerva et al. documented sustained efficacy and high patient satisfaction during long-term follow-up, with repeat injections maintaining functional improvement over several years.²³

Risoud et al. analyzed long-term outcomes of BTX-A for facial palsy sequelae and confirmed that the treatment remained effective across repeated sessions with a mean injection interval of approximately 4 months.¹⁷

Collectively, across all studies, BTX-A administration resulted in consistent improvement of synkinesis, hypertonia, and facial symmetry, as well as enhanced psychosocial outcomes and patient-reported satisfaction.

Functional and quality-of-life outcomes across the included studies are summarized in Table V.^{12, 14-25}

Table V. —Main conclusions of included studies.^{12, 14-25}.

Study	Year	Main conclusions
Cecini et al.14	2013	Global reduction of synkinesis and improved dynamic symmetry.
Choi et al.12	2013	Bilateral injections improve symmetry, QoL, self-esteem, and feeding.
Kim et al.15	2013	Early contralateral BT reduces hypertonia and improves symmetry.
Dall’Angelo et al.16	2014	Improved platysma-related symptoms and static symmetry.
Risoud et al.17	2015	Dose guidelines per muscle on both sides of the face.
Wei et al.18	2017	BT effective in acute and chronic PFP; combine with retraining.
Akulov et al.19	2016	SAQ and SFGS improvement with buccinator treatment.
Neville et al.20	2017	Improvement in SAQ score.
Patel et al.21	2018	Buccinator injection improves oral control and smile.
Shinn et al.22	2019	Higher doses yield better results; best response in oculo-oral synkinesis.
Kanerva et al.23	2021	Buccinator treatment beneficial in almost all patients.
Díaz-Aristizabal et al.24	2021	Improved functionality, reduced synkinesis, better QoL.
Steinhäuser et al.25	2022	Multidisciplinary care improves results in acute and chronic PFP.

Summary of the principal findings and reported outcomes for each study included in the review. QoL: quality of life; BT: botulinum toxin; PFP: peripheral facial paralysis; SAQ: Synkinesis Assessment Questionnaire; SFGS: Sunnybrook Facial Grading System.

Safety and adverse events

BTX-A injections were generally well tolerated. Reported adverse events were mild, transient, and dose-dependent. The most frequent side effects were temporary muscle weakness or ptosis in adjacent regions, mild dry eye, and lip asymmetry due to excessive weakening.^{20, 24}

No systemic complications or long-term adverse effects were observed. Studies using Electromyography (EMG) guided injection techniques reported fewer unwanted effects and more accurate localization.²² Neville et al. recorded only four adverse events among 103 treatment cycles, all self-limited.²⁰

Overall, the compiled evidence supports the efficacy and safety of BTX-A for managing synkinesis and facial asymmetry after PFP. Variability among protocols highlights the need for individualized treatment plans considering disease stage, muscle involvement, and patient expectations.

Summary of findings

BTX-A injections, whether unilateral or bilateral, demonstrated reproducible benefits in restoring facial symmetry, reducing involuntary movements, and improving functional and social outcomes. The consistency of results across prospective and retrospective studies, encompassing more than 1800 patients, underlines the clinical relevance and safety of botulinum toxin therapy in facial palsy rehabilitation.

Summary statement

Taken together, the evidence from the thirteen studies demonstrates that BTX-A is an effective and well-tolerated therapeutic option for the management of sequelae following PFP. Across diverse protocols and patient populations, injections consistently resulted in significant reductions in synkinesis and facial hypertonia, improvement in resting and dynamic symmetry, and better functional and psychosocial outcomes. Although injection patterns and dosages varied, the overall trend supports individualized treatment planning based on muscle involvement and disease stage. These findings support the use of botulinum toxin therapy as part of multidisciplinary facial rehabilitation programs.

Clinical interpretation of findings

PFP produces profound functional, aesthetic, and psychosocial consequences, evolving from acute flaccidity to chronic sequelae such as synkinesis and hypertonia. The evidence reviewed confirms that BTX-A is a valuable therapeutic tool for rebalancing facial dynamics and improving quality of life. Across the included studies, BTX-A was associated with reductions in involuntary contractions, improved facial symmetry, and better objective and patient-reported outcomes. The muscles most frequently treated were the buccinator and platysma, with individualized doses typically ranging from 1 to 2.5 U per point. Bilateral treatment—targeting both the paralyzed and contralateral sides — showed particular benefit for restoring facial harmony. Although protocols varied in dosage, timing, and assessment methods, the overall safety profile of BTX-A remained favorable, with mainly transient and mild side effects. These findings suggest that BTX-A may play an important role within multidisciplinary rehabilitation programs, ideally combined with neuromuscular retraining to promote cortical reorganization and functional recovery. Future studies should focus on standardizing protocols, establishing long-term efficacy, and defining optimal intervention timing to consolidate BTX-A’s role in comprehensive facial reanimation.

PFP remains one of the most complex neuromuscular conditions faced by rehabilitation specialists. Both in its acute and chronic phases, it profoundly affects facial symmetry, motor control, and social interaction. During the acute stage, the loss of voluntary movement in the paralyzed hemiface produces marked flaccidity, functional deficits such as lagophthalmos with corneal ulcer risk, oral incompetence, dysarthria, and accidental biting of the oral mucosa. Aesthetic features – including frontal wrinkle loss, effacement of the nasolabial fold, palpebral ptosis, and general facial atrophy – further contribute to disfigurement and emotional distress.^{2, 3, 8}

In this initial phase, the asymmetry between the two sides of the face is accentuated by the compensatory hyperactivity of the healthy side. The contralateral musculature often undergoes hypertrophy, deepening facial furrows and pulling the oral commissure towards the unaffected side.¹⁸ This imbalance does not only exacerbate aesthetic discrepancies but may also interfere with functional recovery by creating maladaptive movement patterns during reinnervation.

As the nerve begins to regenerate, the process of aberrant reinnervation can lead to synkinesis, spasms, and hypertonia.¹⁹ The most frequent manifestation is the involuntary co-contraction of muscles, such as the zygomaticus major, depressor anguli oris, and platysma, resulting in distortion of voluntary movements. Synkinesis may affect ocular, oral, or cervical regions and typically emerges between the third and sixth months after injury.²⁰ Reported prevalence rates vary from 15% to 55%, depending on lesion severity and rehabilitation strategies. Synkinesis represents one of the strongest predictors of patient-reported quality of life deterioration, given its visible impact on emotional expression and social communication.^{3, 20}

Psychologically, these sequelae induce anxiety, self-consciousness, and social withdrawal. Studies confirm that patients perceive even mild residual asymmetry as disabling, underlining the need for treatments that address both functional and aesthetic components.^{5, 6}

Therapeutic role of botulinum toxin type A

BTX-A has become an essential pharmacologic tool in the management of facial palsy sequelae, particularly for synkinesis, hypertonia, and involuntary spasms.² Acting through the blockade of acetylcholine release at presynaptic nerve terminals, BTX-A produces selective, reversible chemodenervation that weakens targeted muscles without structural damage.^{9, 11} This allows the clinician to rebalance facial tone by suppressing overactive muscles while facilitating voluntary motion in the antagonistic groups.

BTX-A offers several advantages over traditional surgical interventions or systemic medications, including precision, reversibility, and the possibility of dose titration, which is critical in tailoring therapy to each patient’s pattern of asymmetry or synkinesis. The cumulative experience reported across studies confirms that the treatment significantly improves facial symmetry, motor coordination, and patient satisfaction.^{4, 7, 8, 21}

In the analyzed literature, BTX-A was most often administered to the paralyzed side to alleviate synkinetic activity. Nevertheless, increasing evidence supports the efficacy of bilateral treatment to optimize dynamic balance. By modulating the hyperactive contralateral muscles, BTX-A can indirectly enhance movement in the paretic side, potentially through cortical reorganization or decreased mechanical opposition.^{4, 5, 7, 21}

Akulov et al. explored bilateral injections during both the acute and chronic phases, primarily to enhance facial symmetry and prevent compensatory hypertonia.¹⁹ Although most authors recommend BTX-A for the sequelae stage, Akulov’s findings suggest that early symmetrical intervention may improve long-term outcomes by minimizing maladaptive reinnervation. Similarly, Choi et al. demonstrated that injections on both sides of the face reduced synkinesis and contralateral hypertonia, producing significant improvements in symmetry at rest and during movement.^{12, 19}

Muscular targets and injection strategies

The reviewed studies show considerable variability in muscle selection, dosage, and injection patterns, underscoring the importance of individualized protocols. BTX-A can be applied to virtually any facial region affected by synkinesis. The choice of muscles and doses must consider the type and severity of involuntary contraction, muscle volume, and desired cosmetic outcome.^{2, 11}

Buccinator muscle

Three studies specifically investigated the infiltration of the buccinator, indicated in patients with significant oral commissure retraction and poor food manipulation due to involuntary contraction. In these cases, the absence of ipsilateral movement during smiling and chewing led to biting of the oral mucosa and speech disturbances. The initial doses ranged from 0.6 to 2.5 U per point, adjusted according to the degree of retrusion. Wei et al. and Kanerva et al. included simultaneous injections in other unspecified facial muscles, possibly confounding results. In contrast, Patel et al. isolated the effect of the buccinator by comparing BTX-A treatments with and without its inclusion, demonstrating superior functional and aesthetic outcomes when the buccinator was treated.^18-20

Platysma muscle

The platysma, functioning as a depressor of the lower face and lip, is another frequent target. Spasms of this muscle cause tightness, pain, and difficulty smiling.² Most of the reviewed studies included platysmal injections, but only Dall’Angelo et al. assessed outcomes specifically related to this muscle. Using 2.5 U per injection point, they reported substantial improvement in SAQ scores and reduced cervical tension.¹⁶ Shinn et al. later confirmed that higher doses in the platysma – compared to other facial muscles – effectively decreased band formation and enhanced smile amplitude.²²

Dose individualization

Although doses varied across studies, the most commonly used starting dose was 2.5 U per point on both sides of the face. Doses must be carefully adjusted according to the presence of hypertonia, the patient’s muscular anatomy, and aesthetic goals. Typically, higher doses are reserved for contralateral frontal and corrugator muscles to reduce frowning, while smaller doses are employed in the mid- and lower-face regions to prevent an unnatural, paralyzed appearance.^{2, 8, 22}

For chronic synkinesis, gradual dose escalation is advisable, starting low and increasing with repeated sessions until optimal results are achieved. This approach minimizes the risk of overcorrection or undesired weakness. The platysma represents an exception, where more aggressive treatment is often required to suppress powerful depressor activity.^{16, 22}

Shinn et al. observed that higher total doses correlated with improved symmetry and lower synkinesis scores, albeit at a slightly increased risk of transient side effects such as mild ptosis or asymmetry.²² Conversely, excessive dosing in delicate muscles like the orbicularis oculi may induce ptosis or worsen xerophthalmia if not applied conservatively.^{2, 16, 22}

Thus, most authors recommend starting doses between 1 and 2.5 U per point, adjusting progressively depending on muscle mass, degree of hypertonia, and facial asymmetry. Treatment intervals generally ranged between 3 and 6 months, consistent with the pharmacologic duration of BTX-A effects.^{14, 16, 18, 22}

Integration of botulinum toxin therapy within multidisciplinary facial rehabilitation

The management of peripheral facial palsy has progressively evolved from isolated therapeutic interventions toward a comprehensive, multidisciplinary rehabilitation model. Within this framework, BTX-A should not be regarded as a standalone symptomatic treatment, but rather as a complementary tool that facilitates functional recovery when integrated with structured facial rehabilitation programs. Increasing evidence supports the concept that selective chemodenervation can optimize the conditions necessary for effective neuromuscular retraining by reducing involuntary muscle activity and abnormal co-contractions that interfere with voluntary movement execution.^{3, 11, 26}

NMR, mirror therapy, biofeedback, and task-oriented facial exercises constitute the cornerstone of conservative rehabilitation strategies. However, their effectiveness may be limited in the presence of pronounced synkinesis or hypertonia, which mechanically and neurologically disrupt coordinated motor patterns. In this context, BTX-A plays a key role by temporarily weakening overactive muscles, thereby allowing patients to regain better voluntary control of the affected musculature during therapy sessions. This synergistic interaction between pharmacological modulation and active rehabilitation has been highlighted in several studies, which suggest that BTX-A enhances motor relearning by reducing maladaptive antagonist activation and facilitating cortical reorganization.^{4, 8, 26}

From a neurophysiological perspective, the reduction of involuntary muscle activity achieved with BTX-A may promote more efficient sensorimotor integration. By minimizing aberrant afferent feedback generated by synkinetic contractions, patients may develop more accurate motor representations, reinforcing correct movement patterns during repetitive training. This mechanism may partially explain the sustained functional improvements reported in studies combining BTX-A injections with rehabilitation-based interventions.^{3, 8}

Importantly, the integration of BTX-A into multidisciplinary care emphasizes the need for individualized treatment planning. Optimal outcomes depend on close collaboration between physicians experienced in facial injections and rehabilitation professionals who guide motor retraining. Timing of injections, muscle selection, and dosage should be coordinated with therapy goals, ensuring that muscle weakening supports rather than impedes functional recovery.^{11, 26}

Overall, the incorporation of botulinum toxin therapy into comprehensive facial rehabilitation programs reflects a shift toward patient-centered, function-oriented care. Rather than merely suppressing symptoms, BTX-A acts as a facilitator of active rehabilitation, reinforcing its role as a core component within modern facial reanimation strategies.^{4, 5}

Functional and quality-of-life outcomes

Beyond mechanical correction, BTX-A therapy significantly impacts quality of life (QoL) and psychological well-being. Choi et al. supplemented the SFGS with a 20-item questionnaire assessing psychological, social, and functional domains. They demonstrated that BTX-A not only improved facial symmetry but also enhanced self-esteem, social interaction, and ease of eating.¹²

The study by Díaz-Aristizábal et al. utilized the FaCE scale, confirming improvements in total and social subscores, with a notable decrease in SAQ scores after treatment, indicating reduced synkinesis severity.²⁴ These findings emphasize that BTX-A addresses not only motor dysfunction but also psychosocial impairment, aligning with the holistic rehabilitation goals of contemporary facial therapy.^{4, 5}

From a clinical standpoint, treatment planning should also take into account patient expectations, facial dominance, and occupational or social demands, as these factors may influence both therapeutic goals and perceived outcomes. Addressing these aspects during follow-up allows for a more individualized approach and may enhance patient adherence and satisfaction with long-term rehabilitation strategies. This approach reinforces the clinical relevance of rehabilitation.

Across the literature, the SAQ remains the most frequently applied tool, valued for its simplicity and sensitivity to change. However, it exclusively measures synkinesis and does not evaluate contralateral hyperactivity or global symmetry. The SFGS, by contrast, quantifies symmetry at rest and during voluntary movement while accounting for synkinesis magnitude, offering a more comprehensive aesthetic and functional assessment.^{12, 22} For this reason, several authors recommend combining multiple scales to capture both objective and subjective outcomes.^{5, 22}

Furthermore, incorporating patient-reported outcomes is crucial for understanding the real-world benefits of BTX-A. Improvements in social participation, self-image, and daily functioning often outweigh purely quantitative motor gains, confirming that rehabilitation success extends beyond numeric facial symmetry.^{5, 6}

Limitations, variability, and future perspectives

Although the evidence supporting BTX-A efficacy in facial palsy rehabilitation is compelling, several limitations persist. The reviewed studies differ substantially in design, sample size, injection techniques, follow-up duration, and outcome measures, hindering direct comparison. The absence of RCTs with standardized protocols remains a significant gap. In addition, the reproducibility of clinical outcomes appears to be closely related to the experience of the treating team and the consistency of follow-up within rehabilitation programs.

Additionally, many studies report short-term outcomes, leaving the long-term effects and potential cumulative benefits of repeated treatments uncertain. Few authors detail their injection technique, dilution method, or EMG guidance, making replication challenging. While EMG- or ultrasound-guided injections may improve accuracy and reduce adverse events, their use is inconsistently reported.^{5, 11, 22}

Another source of variability lies in the phase of intervention. Most evidence pertains to the chronic sequelae phase, whereas early intervention during partial recovery remains controversial. Some authors caution that premature BTX-A administration could suppress beneficial muscle activity, while others – such as Akulov et al.¹⁹ – suggest that early bilateral use may prevent hypertonic maladaptation.¹⁹ Prospective longitudinal studies are needed to define the optimal timing and duration of therapy.

In terms of safety, adverse effects are infrequent, transient, and typically dose-related. The most common include mild weakness, transient ptosis, or asymmetry, resolving within weeks.^{16, 22, 24} Systemic reactions or immunogenic resistance have not been reported in facial applications. These findings suggest a favorable risk-benefit profile of BTX-A in this indication.

Future research should focus on establishing standardized treatment algorithms defining muscle-specific doses, injection points, and follow-up intervals. Integration of objective outcome measures, such as three-dimensional motion analysis or surface electromyography, may enhance accuracy and reproducibility. Additionally, combining BTX-A with NMR and biofeedback has shown synergistic potential, promoting cortical reorganization and functional restoration.^{4, 8}

The development of new BTX-A formulations and tailored dilution protocols may further improve precision and duration of effect, offering individualized rehabilitation programs. Multicenter RCTs with unified endpoints are essential to confirm efficacy, durability, and cost-effectiveness of these strategies.

Summary

In summary, BTX-A represents a valuable therapeutic option in the modern rehabilitation of peripheral facial palsy. Across the analyzed literature, BTX-A consistently demonstrates the ability to reduce synkinesis, relieve hypertonia, restore symmetry, and enhance quality of life. The most effective results arise from individualized dosing protocols, bilateral treatment when indicated, and integration with physiotherapeutic techniques.

While methodological variability persists, the convergence of evidence supporting BTX-A suggests that it may act as both a symptomatic and functional therapy, bridging the gap between medical aesthetics and neurorehabilitation. Future studies should aim to harmonize treatment protocols, validate comprehensive outcome measures, and clarify the optimal timing of intervention to maximize long-term recovery.

Ultimately, the rehabilitation of facial palsy extends beyond muscle relaxation – it restores identity, confidence, and social participation, reaffirming the therapeutic relevance of botulinum toxin within a multidisciplinary approach to facial reanimation.

Conclusions

BTX-A has emerged as a valuable therapeutic option in the multidisciplinary management of PFP. By selectively modulating muscle activity, it effectively reduces synkinesis, hypertonia, and facial asymmetry, while contributing to improvements in functional outcomes and psychosocial well-being. The evidence synthesized in this review underscores the importance of individualized treatment strategies, including tailored dosing, bilateral application when indicated, and integration with neuromuscular retraining. Despite heterogeneity among studies, the available evidence suggests consistent clinical benefits and a favorable safety profile. Nevertheless, the predominance of observational studies underscores the need for additional randomized controlled trials with standardized protocols and long-term follow-up to further clarify optimal treatment strategies for facial reanimation therapy.