Spatial functional reorganizations can serve as potential biomarkers of post facial palsy synkinesis.

Facial palsy can result in a serious complication known as facial synkinesis, causing both physical and psychological harm to the patients. There is growing evidence that patients with facial synkinesis have brain abnormalities, but the brain mechanisms and underlying imaging biomarkers remain unclear. Here, we employed functional magnetic resonance imaging (fMRI) to investigate brain function in 31 unilateral post facial palsy synkinesis patients and 25 healthy controls during different facial expression movements and at rest. Combining surface-based mass-univariate analysis and multivariate pattern analysis, we identified diffused activation and intrinsic connection patterns in the primary motor cortex and the somatosensory cortex on the patient's affected side. Further, we classified post facial palsy synkinesis patients from healthy subjects with favorable accuracy using the support vector machine based on both task-related and resting-state functional magnetic resonance imaging data. Together, these findings indicate the potential of the identified functional reorganizations to serve as neuroimaging biomarkers for facial synkinesis diagnosis.

Decreased ACKR3 (CXCR7) function causes oculomotor synkinesis in mice and humans.

Oculomotor synkinesis is the involuntary movement of the eyes or eyelids with a voluntary attempt at a different movement. The chemokine receptor CXCR4 and its ligand CXCL12 regulate oculomotor nerve development; mice with loss of either molecule have oculomotor synkinesis. In a consanguineous family with congenital ptosis and elevation of the ptotic eyelid with ipsilateral abduction, we identified a co-segregating homozygous missense variant (c.772G>A) in ACKR3, which encodes an atypical chemokine receptor that binds CXCL12 and functions as a scavenger receptor, regulating levels of CXCL12 available for CXCR4 signaling. The mutant protein (p.V258M) is expressed and traffics to the cell surface but has a lower binding affinity for CXCL12. Mice with loss of Ackr3 have variable phenotypes that include misrouting of the oculomotor and abducens nerves. All embryos show oculomotor nerve misrouting, ranging from complete misprojection in the midbrain, to aberrant peripheral branching, to a thin nerve, which aberrantly innervates the lateral rectus (as seen in Duane syndrome). The abducens nerve phenotype ranges from complete absence, to aberrant projections within the orbit, to a normal trajectory. Loss of ACKR3 in the midbrain leads to downregulation of CXCR4 protein, consistent with reports that excess CXCL12 causes ligand-induced degradation of CXCR4. Correspondingly, excess CXCL12 applied to ex vivo oculomotor slices causes axon misrouting, similar to inhibition of CXCR4. Thus, ACKR3, through its regulation of CXCL12 levels, is an important regulator of axon guidance in the oculomotor system; complete loss causes oculomotor synkinesis in mice, while reduced function causes oculomotor synkinesis in humans.

Long-term therapy with botulinum toxin in facial synkinesis: Retrospective data analysis of data from 1998 to 2018.

OBJECTIVES: Treatment with botulinum toxin A (BoNT) is the therapy of choice for many patients with facial synkinesis. Repeated injections relieve hypertonicity and hyperkinesis of reinnervated mimic muscles. Aim of the study was to prove if the injection regime and dosage of BoNT change during long-time therapy. DESIGN: Retrospective analysis of patients´ data, who were treated for synkinesis with BoNT from 1998 to 2018. SETTING: Tertiary referral facial nerve centre. PARTICIPANTS: Injection pattern of BoNT was based on clinical symptoms, observations of the specialist and on previous treatment pattern. Onabotulinumtoxin (OnaBoNT), Incobotulinumtoxin (IncoBoNT) and Abobotulinumtoxin (AboBoNT) were available for treatment. Patients consulted our department for following treatment as soon as the symptoms re-occurred. MAIN OUTCOME MEASURES: Change in dosage and injection pattern, the time intervals between treatments over the entire therapy period. RESULTS: Seventy-three patients were repeatedly injected. The median number of treatments was 18, the median treatment interval was 3.0 months. During the initial treatment, orbicularis oculi and the mentalis muscles were the most frequently injected muscles (94%). During repeated treatment, the number of injected muscles increased significantly (P < .0001), whereas the dose per muscle remained stable. The initial dose was 24 U (95%-CI 22-27 U) for OnaBoNT and IncoBoNT; 69 U for AboBoNT(95%-CI 44-94 U). We observed a significant increase in dosage for OnaBoNT and IncoBoNT (P < .0001) during the long-term therapy. The time intervals between treatments were stable for all three BoNT preparations (P > .05). CONCLUSIONS: We observed significant change in treatment dose and injection pattern of BoNT in patients with facial synkinesis. These results provide an orientation in dose finding and injection regimen of BoNT in the long-term course of therapy.

Congenital Oculonasal Synkinesis.

A 4-year-old girl with maxillary hypoplasia, intermittent exotropia, and high myopia displayed congenital oculonasal synkinesis. We examine the implications for pathogenesis of these disparate craniofacial findings.

Motor Control Deficits in Facial Synkinesis Patients: Neuroimaging Evidences of Cerebral Cortex Involvement.

Objective: Facial synkinesis is a severe sequelae of facial nerve malfunction. Once the synkinesis is established, it is extremely difficult for patients to recover. Given that the restoration of motor or sensory function after peripheral nerve injury was closely related with cortical plasticity, we investigated cortical plasticity in facial synkinesis patients by the frequency-specific data which remains largely uncharacterized. Materials and Methods: Resting-state fMRI was conducted in 20 facial synkinesis patients and 19 healthy controls, and the amplitude of low-frequency fluctuation (ALFF) in five different frequency bands (slow-6: 0-0.01 Hz; slow-5: 0.01-0.027 Hz; slow-4: 0.027-0.073 Hz; slow-3: 0.073-0.167 Hz; and slow-2: 0.167-0.25 Hz) was calculated, respectively. And the relationship between ALFF and clinical outcomes was also analyzed. Results: Comparing with the healthy controls, facial synkinesis patients showed significantly different ALFF values, mainly in the sensorimotor areas. Furthermore, increased ALFF of the ipsilateral insula in the slow-6 band was significantly related with better facial nerve function. Conclusion: Increased ALFF values in the ipsilateral insula might reflect an abnormal state of hypercompensation in motor control of facial synkinesis patients. It provided valuable spatial information about the functionally aberrant regions, which implied the possible involvement of motor control system in facial synkinesis.

Can the Jankovic-assessment be used as an alternative to electromyography? A cross-sectional study on facial dystonia patients treated with Botulinum toxin.

PURPOSE: This study aims to quantitatively compare the Jankovic assessment (JA) with electromyography (EMG)-based measures for assessing changes in facial movements in patients with facial dystonia. MATERIALS AND METHODS: Thirteen patients (five males and eight females) affected with different forms of facial dystonia (hemifacial spasm and synkinesis) participated in this study. All patients were treated with Botulinum Toxin (BTX) and evaluated with the JA scale and EMG-based measures, including motor unit potentials (MUP) latency and presence of polyphasic potentials before and after BTX injection. Correlation between the JA scores and the EMG-based measures was calculated. Statistical analysis was performed with the Pearson test. RESULTS: Correlation between the JA scores and the EMG-based measures was found to be statistically significant, both before and after treatment with BTX. CONCLUSION AND RELEVANCE: JA scores significantly correlated with more objective EMG-based measures, suggesting that the JA scale can be used to assess facial movement changes, for example elicited by a treatment such as BTX injection. Thus, in facial dystonia patients, the JA scale may be used for evaluating treatment outcomes as a valid and low-cost alternative to EMG.

Synkinesis Between Orbicularis Oculi and Procerus Muscles: Video Presentation of an Unusual Type of Aberrant Innervation after Cosmetic Rhinoplasty.

BACKGROUND: Synkinesis is a recognized complication following peripheral facial nerve paralysis. Different types of synkinesis have been described, with oral-ocular and ocular-oral synkinesis being the most common. Ocular-nasal synkinesis has been reported in two patients following cosmetic rhinoplasty. However, synkinesis between the orbicularis oculi and procerus muscles has not been reported by now. METHODS: This is an interventional case report. RESULTS: Two women, aged 42 and 37 years, presented with unilateral contraction of the medial eyebrow muscles (procerus) with spontaneous or voluntary blinking, 4 and 5 months after cosmetic rhinoplasty, respectively. Both were successfully treated with injection of botulinum toxin A. CONCLUSIONS: Surgical trauma is inevitable during every procedure, including rhinoplasty, and may damage the fine structures including branches of the facial nerve innervating the muscles. Gentle tissue handling may minimize iatrogenic injury to the fine motor branches of the facial nerve and prevent subsequent aberrant innervation and synkinesis. Botulinum toxin A injection can effectively, yet temporarily, resolve the unintentional contractions and provide significant patient comfort. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the table of contents or the online instructions to authors www.springer.com/00266 .

Synkinetic wrist extension in distinguishing cortical hand from radial nerve palsy.

We describe a patient with pseudoradial nerve palsy caused by acute ischaemic stroke ('cortical hand') to emphasise how preserved synkinetic wrist extension following fist closure can distinguish this from peripheral causes of wrist drop.

Objective assessment of the reliability of the House-Brackmann and Fisch grading of synkinesis.

The objective of this paper is to assess synkinesis associated with post paretic voluntary facial movements using the objective OSCAR method and to investigate the correlation between synkinesis and paresis to compare the objective results with the subjective scaling systems of Fisch and House-Brackmann. The development of an objective assessment of synkinesis with the OSCAR method is focused on the clinically most relevant eye-mouth and forehead-mouth synkinetic movements. Thirteen patients with unilateral facial paralysis and synkinesis of the University Hospital Zurich were examined. Two types of clinically relevant facial synkinesis were found: a maximal synkinesis and a relative synkinesis. Neither Synkinesis-Index correlates well with the underlying degree of global facial palsy. The relative Synkinesis-Index (rSI) correlates well with the subjective evaluation of synkinesis according to the Fisch Grading, but shows a poor correlation with the traditional House-Brackmann grading. Therefore a single scaling index combining the degree of facial nerve palsy and synkinesis is inappropriate and we propose the use of two independent scaling systems for the evaluation of facial palsy: one for the voluntary facial movements, the other for the involuntary synkinetic movements. The adequate evaluation of the post paretic face should include the results of both scaling systems.

Facial synkinesis as a first symptom of multiple sclerosis.

A 39-year-old woman was admitted to hospital because of a sensory hemisyndrome caused by a contrast-enhancing demyelinating lesion of the cervical cord. MRI, CSF examination and subsequent clinical and neuroradiological follow-up led to the diagnosis of multiple sclerosis. The patient had noticed an involuntary contraction of a small muscle fascicle on the right side of the chin for a year. Electromyographic and video recordings confirmed the synkinesis between the orbicularis oculi and lower facial muscles, a finding distinct from the myokymic discharges reported in multiple sclerosis and more similar to the synkinesis associated with hemifacial spasm.

Subjective and Objective Measures in the Treatment of Hemifacial Spasm With OnabotulinumtoxinA.

PURPOSE: To evaluate the Sunnybrook Facial Grading System (SFGS) and Facial Clinimetric Evaluation (FaCE) Scale Instrument outcomes when treating hemifacial spasm (HFS) with onabotulinumtoxinA. METHODS: An Institutional Review Board-approved retrospective review of records of 66 HFS patients treated with onabotulinumtoxinA. SFGS and FaCE surveys were completed prior to onabotulinumtoxinA therapy and at 1 month follow up. Surveys were analyzed for differences using paired Student t tests, with statistical significance set at p < 0.05. Correlations were determined using Spearman correlation (rs), with coefficients of ≥0.40 or ≤-0.40 considered significant. RESULTS: There were 22 complete data sets. SFGS composite score improved from mean, 56.9 (SD, 12.3) to 63.6 (SD, 12.3), p < 0.01. SFGS subdomain synkinesis score significantly improved (p < 0.01). The FaCE scale subdomain oral function significantly worsened (p = 0.05). The Δ pre-/post-SFGS composite score did not correlate with the Δ pre-/post-FaCE composite score (rs = 0.24). There was a significant positive correlation between SFGS composite score and FaCE social function score (rs = 0.462, p = 0.03) and between SFGS voluntary movement score and FaCE social function score (rs = 0.477, p = 0.03). Subgroup analysis of single FaCE questions demonstrated no statistical change in subjective dry eye (p = 0.30). CONCLUSIONS: There was an improvement in social functioning in treated HFS patients, which positively correlated with improvement in overall objective voluntary facial movement. There was no statistical difference in subjective dry eye symptoms. The overall SFGS composite score improved following treatment of HFS with botulinum toxin. This information can be used when counseling expected outcomes in HFS patients treated with onabotulinumtoxinA.

Treating Buccinator With Botulinum Toxin in Patients With Facial Synkinesis: A Previously Overlooked Target.

OBJECTIVE: Synkinesis after facial nerve injury produces functional and cosmetic concerns for patients. The purpose of this study was to review the authors' experience of treating buccinator synkinesis with botulinum toxin. METHODS: This was a retrospective medical records review. All patients seen at the University of Wisconsin Neuromuscular Retraining Clinic who were treated with botulinum injections to the buccinator muscle were included. After a period of neuromuscular retraining lasting 6 to 12 months, botulinum injections were administered to the anterior, middle, and/or posterior aspect of buccinator by the senior author via an intraoral approach. The sites and dosage of the injections depended substantially on input from the therapist overseeing the patient's neuromuscular retraining therapy. Data on patient age, gender, indication for treatment, location and dose of botulinum administration, and outcome were collected. The Synkinesis Assessment Questionnaire (SAQ) was used as a patient-reported outcome measure. Descriptive statistics were computed for all recorded variables. RESULTS: A total of 42 patients with synkinesis involving the buccinator were treated. Female-to-male ratio was 9:1, and follow up ranged from 5 months to 18 years. The indications for treatment included significant retraction and immobility of the affected oral commissure at rest and during volitional and spontaneous facial expressions, difficulty manipulating food during mastication, and biting the inside of the affected cheek. Mean total dose of botulinum administered to buccinator per session was 2.0 units (range, 0.6-2.5 units). SAQ scores improved from a mean of 66.6 preinjection to 45.0 postinjection. In general, patient satisfaction with the procedure was high, and there were no serious complications. CONCLUSIONS: To the authors' knowledge, this is the first report of a cohort of patients with buccinator synkinesis treated with botulinum toxin. This treatment has become a valuable adjunct in the comprehensive management of patients with facial synkinesis.

Presumed canine trigemino-abducens synkinesis in a dog.

A ten-year-old male neutered Rhodesian ridgeback cross dog was presented for the investigation of abnormal bilateral protrusion of the third eyelid when chewing. Physical, ophthalmological, and neurological examinations were unremarkable. Thoracic radiographs, abdominal ultrasound, and magnetic resonance of the brain and orbits failed to reveal any abnormalities. Cerebrospinal fluid analysis revealed elevated protein, but the nucleated cell count was normal. trigemino-abducens synkinesis was presumptively diagnosed. Aetiopathogenesis of this condition is discussed. To the authors' knowledge, this is the first report of presumed trigemino-abducens synkinesis in a dog.

Congenital trochlear-oculomotor synkinesis.

Synkinesis of the extraocular muscles forms a subset of congenital ocular motility abnormalities termed congenital cranial dysinnervation disorders. Synkinesis most frequently involves the abducens or oculomotor nerves and rarely the trochlear nerve. Only 3 such patients have been described in the literature. We report an isolated case of trochlear-oculomotor synkinesis in a healthy 6-year-old boy and discuss the proposed pathophysiology of this disorder.

A rare phenomenon: oculonasal synkinesis.

Oculonasal synkinesis is the simultaneous contraction of the orbicularis oculi and the compressor narium minor muscles. The etiology of this phenomenon is still unclear; congenital and traumatic reasons are considered to be responsible. Here we report a case of oculonasal synkinesis.

Automated analysis of spontaneous eye blinking in patients with acute facial palsy or facial synkinesis.

Although patients with facial palsy often complain of disturbed eye blinking which may lead to visual impairment, a blinking analysis is not part of routine grading of facial palsy. Twenty minutes of spontaneous eye blinking at rest of 30 patients with facial palsy (6 with acute palsy; 24 patients with facial synkinesis; median age: 58 years, 67% female), and 30 matched healthy probands (median age: 57 years; 67% female) was smart phone video recorded. A custom computer program automatically extracted eye measures and determined the eye closure rate (eye aspect ratio [EAR]), blink frequency, and blink duration. Facial Clinimetric Evaluation (FaCE), Facial Disability Index (FDI) were assessed as patient-reported outcome measures. The minimal EAR, i.e., minimal visible eye surface during blinking, was significantly higher on the paretic side in patients with acute facial palsy than in patients with synkinesis or in healthy controls. The blinking frequency on the affected side was significantly lower in both patient groups compared to healthy controls. Vice versa, blink duration was longer in both patient groups. There was no clear correlation between the blinking values and FaCE and FDI. Blinking parameters are easy to estimate automatically and add a functionally important parameter to facial grading.

Prognostic value of electroneurography using the midline method for predicting the development of synkinesis after peripheral facial palsy.

OBJECTIVE: The prognostic value of electroneurography (ENoG) for predicting the incidence of synkinesis is reportedly about 40 % using the formal standard method (ENoG-SM). However, the prognostic value of ENoG using the newly developed midline method (ENoG-MM) has not been determined. The aim of this study was to demonstrate the optimal prognostic value and advantages of ENoG-MM for predicting the incidence of synkinesis. METHODS: Participants were 573 patients treated for peripheral facial palsy including Bell's palsy or Ramsay Hunt syndrome. We investigated the clinical presence of any oral-ocular or ocular-oral synkinesis from the medical records. ENoG-MM and ENoG-SM were performed 10-14 days after symptom onset. In ENoG-MM, compound muscle action potentials were recorded by placing the anode on the mental protuberance and the cathode on the philtrum. In ENoG-SM, electrodes were placed on the nasolabial fold. Synkinesis was clinically assessed at the end of follow-up or at >1 year after onset. The sensitivity and specificity of ENoG values for predicting the incidence of synkinesis were compared between ENoG-MM and ENoG-SM at every 5 % around 40 % (range, 30-50 %). RESULTS: At every 5 % of ENoG values around 40 %, ENoG-MM provided higher sensitivity and lower specificity for predicting the incidence of synkinesis compared with ENoG-SM. In particular, when the cut-off value was set at 45 %, sensitivity was 100 % and 95.3 % with ENoG-MM and ENoG-SM, respectively. CONCLUSION: In peripheral facial palsy, ENoG-MM offered higher sensitivity than ENoG-SM for predicting synkinesis. ENoG-MM is useful for screening patients at risk of developing synkinesis. In clinical practice, an ENoG-MM cut-off value of 45 % must be the optimal prognostic value because of the 100 % sensitivity.