Bilateral Congenital Trochlear-Oculomotor Synkinesis in a 5-Month-Old Infant.

Oculomotor synkinesis is an unusual phenomenon that encompasses various presentations with few associations reported in the literature. It can occur with or without a previous setting of oculomotor nerve injury. The authors present the first reported case of bilateral congenital trochlear-oculomotor synkinesis in a 5-month-old infant. [J Pediatr Ophthalmol Strabismus. 2024;61(5):e50-e53.].

Effects of basic movements and gait in the case of homolateral imitative synkinesis.

BACKGROUND: Homolateral Imitative Synkinesis (HIS) is a rare form of associative movement between the ipsilateral upper and lower limbs. The incidence of HIS or its correlation with various movements remains uninvestigated. This study expounds on the characteristics of HIS, the frequency at which it occurs, and its relationship with movement, particularly walking. METHODS: This study included 1328 patients with acute stroke admitted to our healthcare facility between October 2019 and February 2022. We evaluated the severity of motor paralysis and sensory impairment in instances where HIS manifested, and assessed the relationship between HIS, basic activities, and gait. RESULTS: HIS was observed in 13/1328 patients. Motor paralysis was mild in all the cases. Each patient displayed a degree of sensory impairment, albeit of varying severity. HIS did not manifest during basic activities but was evident during walking movements in five instances. These patients displayed involuntary repetitive lifting of their upper limbs during the swing phase of their gait. Some individuals expressed discontent with involuntary upper-limb movements, citing them as contributors to a suboptimal gait. CONCLUSIONS: This study identified HIS as a rare syndrome, manifesting at a rate of 0.9%. Focus was more common in patients with damage to the thalamus and parietal lobe. No manifestations of the HIS occurred during basic activities, suggesting a weak correlation between the HIS and such activities. Certain patients exhibit HIS during gait, report suboptimal gait, and have an increased risk of falls, potentially influencing their gait proficiency.

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.

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.

Effect of Underlying Mental Health Disorders on the Correlation Between Patient- and Surgeon-Graded Synkinesis Scores.

Background: Little is known about how depression and appearance anxiety affect patient reporting of synkinesis severity. Learning/Study Objective: Measure prevalence of depression and appearance anxiety in facial synkinesis and correlations between subjective and surgeon-graded synkinesis severity. Design Type: Prospective cohort. Methods: Patients with synkinesis volunteered and completed: Synkinesis Assessment Questionnaire (SAQ), facial clinimetric evaluation (FaCE) scale, Center for Epidemiological Studies Depression Scale (CES-D), and Fear of Negative Appearance Evaluation Scale (FNAES). Standardized videos were scored by facial plastic surgeons using Sunnybrook Scale and eFaCE. Multivariate linear regression was used to compare patient- and surgeon-graded metrics. Results: One hundred patients participated, 91 were female. Mean age was 56.4 (12.3). Eight percent identified as Black and 87% White. The most common nerve injury etiology was idiopathic (47%). Mean synkinesis duration was 7.6 years (6.2). Twenty percent and 15% reported history of an anxiety or depressive disorder, respectively. Patient (SAQ, FaCE) and clinician (Sunnybrook, eFaCE) scores were correlated (Pearson's r 0.223-0.294, p < 0.05). Upon adjusting for CES-D/FNAES, correlations between most patient and clinician metrics became stronger. As CES-D and FNAES worsened, patient-clinician correlations weakened. Conclusions: Depression and appearance anxiety may affect patient reporting of synkinesis severity. Worse mental health scores may decorrelate patient and clinician synkinesis assessments.

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.

Long-term stable efficacy of botulinum toxin A in facial movement disorders with no need for increasing dose.

ABSTRACT: Botulinum toxin A is considered an effective treatment for involuntary facial movements. We examined whether treatment efficacy maintained or changed over time with two products, Botox and Dysport, in patients with hemifacial spasm, facial synkinesis and benign essential blepharospasm.We retrospectively investigated 87 consecutive patients (51 women, 36 men) who had undergone treatment for ≥6 years. Long-term effects, as well as side effects of Botox or Dysport local injections were evaluated. The first three treatments were considered the titration period and not taken into account when testing for dose changes.Mean treatment duration was 10 years (range 6-11, SD 1.0), 2441 treatments were administered, 1162 with Botox and 1279 with Dysport, the two brands were interchanged as needed. Good to full improvement was seen in 90% of patients both with both brands. Injection doses and treatment responses were consistent during the study with both drugs. No major side effects were reported, and relatively few minor adverse events were reported, with clear reduction from the titration period (6.1%), to the remainder of the study (3.9%).Botulinum toxin (BTX-A) is a satisfactory long-term treatment without need for dose increase over. Both Botox and Dysport were effective when used interchangeably.

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.

Abnormal Laryngeal Electromyography Findings in Asymptomatic Adults Across the Age Spectrum.

OBJECTIVES/HYPOTHESIS: Laryngeal electromyography (LEMG) is a diagnostic tool for patients with suspected neurogenic abnormalities of the larynx. LEMG is often used with the assumption that any abnormality is symptom-/disease-related. We sought to determine the prevalence of abnormal LEMG findings in a group of healthy asymptomatic adults across a large age spectrum. STUDY DESIGN: Open, prospective study, gender-match and age balanced by decade. METHODS: Forty-six healthy participants (age 20-78) underwent LEMG, including 178 muscles. Participants had no history of voice problems, normal VHI-10, and normal flexible laryngoscopy. Qualitative and quantitative LEMG (bilateral) were performed involving the thyroarytenoid-lateral cricoarytenoid muscle complex (TA-LCA) and cricothyroid (CT) muscles. LEMG parameters included evaluation for fibrillation potentials, sharp waves, reduced recruitment, polyphasic potentials, electrical synkinesis, and measurement of turns per second. RESULTS: Of participants, 4% had at least one abnormal qualitative finding (slightly reduced recruitment or two to three discrete polyphasic potentials). There were no findings of fibrillation potentials or sharp waves. There were no abnormal qualitative findings in the CT muscles tested. Of participants, 16% had at least one abnormal synkinesis finding. LEMG qualitative abnormalities and quantitative abnormalities do not appear to correlate with gender or age. CONCLUSION: Abnormal qualitative and quantitative LEMG findings were uncommon and minor in severity in our group of asymptomatic healthy adults. The likelihood of abnormal LEMG results in asymptomatic adults was 2.2% for qualitative findings, 9.3% for synkinesis, and 5.4% for turns/s. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:2065-2069, 2021.

Buccinator synkinesis treated by botulinum toxin in facial palsy and hemifacial spasms.

OBJECTIVE: To assess botulinum toxin treatment for buccinator muscle synkinesis including: how often the synkinesis was troublesome; who benefitted and how from the treatment; and what were the adverse effects, ideal dosage, and injection site. SUBJECTS AND METHODS: Facial palsy (FP) patients and patients with hemifacial spasms who were attending for multiple site botulinum-toxin treatment for facial sequelae were assessed for buccinator synkinesis. The study group comprises those experiencing buccinator synkinesis with associated bothering symptoms who were willing to try injection also to the buccinator muscle. RESULTS: During 9/2017-12/2019, 126 different patients with facial sequelae were treated with multiple-site botulin-toxin injections by the author. Of them, 83 (66%) received injection also for buccinator synkinesis and 66/82 (80%) wanted to continue with the buccinator injections. The most remarkable results were seen with FP patients biting the mucus membrane of their cheek: usually the biting ceased totally. Patients with powerful hemifacial cheek spasms also experienced cessation of the spasms, contrasting any previous treatments. Adverse effects were mostly mild: slight weakness of the corner of the mouth or additional leakage of saliva or liquids. Only a few patients experienced more pronounced adverse effects. The most posterior contracting part of the buccinator muscle proved to be the best site for the injection. CONCLUSIONS: Buccinator synkinesis was very common and its treatment gave many patients additional relief from facial sequelae symptoms. Professionals treating patients with synkinesis and hemifacial spasms should add well-tolerated buccinator injections to their repertoire of injection sites.

Crumley's Classification of Laryngeal Synkinesis: A Comparison of Laryngoscopy and Electromyography.

OBJECTIVES/HYPOTHESIS: Applying the principles of misdirected nerve regeneration to the larynx, Roger Crumley in 1989 coined the term laryngeal synkinesis (LS) which he later (2000) classified into 4 types (type I - good voice, type II - involuntary twitches and poor voice, type III - adduction during inspiration, type IV - abduction during phonation). Neurophysiological data were not available for all LS patients at that time. The current study was undertaken to utilize and test the Crumley classification for a clinical interrater comparison and, secondly, compare predicted with actual laryngeal electromyography (LEMG) results. STUDY DESIGN: Descriptive study. METHODS: Laryngoscopic and LEMG data of patients with unilateral vocal fold paralysis (VFP) of 6 months duration or longer were combined for retrospective evaluation. Forty-five data sets were available for laryngoscopic classification by two local laryngologists and by Roger Crumley. Twenty-three data sets with complete thyroarytenoid (TA) and posterior cricoarytenoid (PCA) - EMG data were used to compare predicted with actual LEMG results. RESULTS: Local laryngologists were able to classify 24 of 45, Crumley 30 of 45 cases into one of the 4 synkinesis types. There was substantial agreement between examiners (Cohens Kappa 0.66 [P < .001]). Comparison of predicted and actual LEMG data showed only moderate agreement. EMG sykinesis rates were lower in TA than in PCA and highest in Crumley type I cases. CONCLUSION: The Crumley classification is helpful in describing and understanding synkinesis. It does not always correlate predictably with actual LEMG data. A complete LEMG mapping of all intrinsic muscles may improve understanding of chronic VFP. LEVEL OF EVIDENCE: 4. Laryngoscope, 131:E1605-E1610, 2021.

Syngeneic Transplantation of Rat Olfactory Stem Cells in a Vein Conduit Improves Facial Movements and Reduces Synkinesis after Facial Nerve Injury.

BACKGROUND: Posttraumatic facial paralysis is a disabling condition. Current surgical management by faciofacial nerve suture provides limited recovery. To improve the outcome, the authors evaluated an add-on strategy based on a syngeneic transplantation of nasal olfactory stem cells in a rat model of facial nerve injury. The main readouts of the study were the recording of whisking function and buccal synkinesis. METHODS: Sixty rats were allocated to three groups. Animals with a 2-mm facial nerve loss were repaired with a femoral vein, filled or not with olfactory stem cells. These two groups were compared to similarly injured rats but with a faciofacial nerve suture. Olfactory stem cells were purified from rat olfactory mucosa. Three months after surgery, facial motor performance was evaluated using video-based motion analysis and electromyography. Synkinesis was assessed by electromyography, using measure of buccal involuntary movements during blink reflex, and double retrograde labeling of regenerating motoneurons. RESULTS: The authors' study reveals that olfactory stem cell transplantation induces functional recovery in comparison to nontransplanted and faciofacial nerve suture groups. They significantly increase (1) maximal amplitude of vibrissae protraction and retraction cycles and (2) angular velocity during protraction of vibrissae. They also reduce buccal synkinesis, according to the two techniques used. However, olfactory stem cell transplantation did not improve axonal regrowth of the facial nerve, 3 months after surgery. CONCLUSIONS: The authors show here that the adjuvant strategy of syngeneic transplantation of olfactory stem cells improves functional recovery. These promising results open the way for a phase I clinical trial based on the autologous engraftment of olfactory stem cells in patients with a facial nerve paralysis.

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.

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.

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.