Comparison of preseptal and pretarsal injections of botulinum toxin in the treatment of blepharospasm and hemifacial spasm

Although the beneficial effect of subcutaneous injections of botulinum toxin type A (BTX-A) is well known in both blepharospasm and hemifacial spasm, the position of the injection sites around the orbicularis oculi may influence the effectiveness and side effects. Here we report results of preseptal and pretarsal BTX-A injections in 53 patients (25 blepharospasm and 28 hemifacial spasm) in whom we used both injection techniques successively. Pretarsal injections were used in 102 out of 186 treatments in blepharospasm group and in 84 out of 202 treatments in hemifacial spasm group. Pretarsal BTX-A treatment produced significantly higher response rate and longer duration of maximum response in both patient groups. This technique was also associated with a lower frequency of major side effects such as ptosis. We concluded that injections of BTX-A into the pretarsal, rather than the preseptal portion of the orbicularis oculi is more effective for treatment of involuntary eyelid closure due to contractions of this muscle. Received: 15 January 2001, Received in revised form: 11 May 2001, Accepted: 17 May 2001     

Pretarsal blepharospasm: Clinical and electromyographic characteristics

ObjectiveTo describe the clinical and electromyographic characteristics of blepharospasm caused by selective involvement of the pars pretarsalis of the orbicularis oculi muscle.MethodsClinical assessment and simultaneous electromyographic recordings from levator palpebrae superioris and pars orbitaria and pretarsalis of orbicularis oculi muscles were performed in patients with blepharospasm and primary failure to botulinum toxin injections. Patients with selective abnormal electromyographic activity of the pars pretarsalis of the orbicularis oculi muscle were identified and treated with selective pretarsal injections of botulinum toxin.ResultsWe found 24 patients with pretarsal blepharospasm confirmed by the electromyographic assessment. All of them were functionally blind. Three clinical-electromyographic patterns were identified: (a) Impairment of eyelid opening; (b) Increased blinking; (c) Spasms of eye closure combined with varying degrees of excessive blinking and impairment of eye-opening. Pretarsal injections of botulinum toxin induced a significant improvement in all patients and 50 % regained normal or near-normal vision. The clinical improvement was sustained after repeated pretarsal injections.ConclusionsPretarsal blepharospasm can be suspected on clinical grounds and it can be confirmed by electromyographic recordings.SignificanceRecognition of this type of blepharospasm is important because of its excellent response to botulinum toxin injections applied into the pretarsal part of the orbicularis oculi muscle.     

Pretarsal application of botulinum toxin for treatment of blepharospasm.

The response to botulinum toxin type A was compared after two injection techniques in 45 patients with blepharospasm. Initially, patients were treated according to a triple injection technique; two injections into the upper eyelid and one injection into the lower eyelid. Subsequently, without altering the dose, the same patient group received two further injections into the pretarsal portion of the orbicularis oculi muscle of the upper lid. Triple injections were given in 227 treatments, of which 81% were successful. Mean duration of benefit was 8.5 weeks. Additional pretarsal injections were given in 183 treatment sessions. The number of successful treatments significantly increased, to 95% (P < 0.001), and the mean duration of benefit increased to 12.5 weeks (P < 0.001). Ptosis occurred significantly less often after pretarsal injections (P < 0.01). Patients with combined blepharospasm and involuntary levator palpebrae inhibition responded better to the pretarsal injection technique.     

A comparative crossover study on the treatment of hemifacial spasm and blepharospasm: preseptal and pretarsal botulinum toxin injection techniques

Hemifacial spasm (HFS) and benign essential blepharospasm (BEB) are chronic and disabling abnormal craniofacial movements that produce involuntary eyelid twitching and closure. The efficacy and safety of botulinum toxin type A (BoNT-A) injections have been accepted and widely used for the treatment of HFS and BEB. However, different injection sites may influence the effectiveness, doses, and side effects. The aim of this study is to compare the efficacy, patient satisfaction, and complications of low-dose BoNT-A injections between injection at the preseptal (PS) and the pretarsal (PT) portion of the orbicularis oculi muscle. A total of 40 patients, 31 patients with HFS and 9 patients with BEB, participated in this study. Each patient received both PS and PT BoNT-A injections in a crossover design study. Latency to response, duration of improvement, the Jankovic Rating Scale (JRS), self-response scale, patient satisfaction scale, and complications were compared. Low-dose injections of BoNT-A at the PT portion produced a significantly higher response rate in terms of latency to response, duration of improvement, JRS, self-response scale, and patient satisfaction scale than the PS injections. Major side effects including ptosis and droopy eyelid were observed only after the PS injections. These findings confirmed that low-dose injections of BoNT-A at the PT portion provide more efficacy, patient satisfaction, and fewer complications than the PS injections for the treatment of involuntary eyelid twitching and closure in patients with HFS and BEB.     

Morphological substrate for eyelid movements: innervation and structure of primate levator palpebrae superioris and orbicularis oculi muscles

The levator palpebrae superioris and orbicularis oculi are antagonistic muscles that function during movements of the eyelid. The levator also functions in conjunction with superior and inferior rectus muscles in coordinated eye/lid movements. The present study examined the innervation and morphology of these muscles in Cynomolgous monkeys (Macaca fascicularis) in order to provide a better understanding of the anatomical substrate for lid movements. Motoneurons innervating the levator and orbicularis muscles were identified and localized by retrograde transport of WGA/HRP and HRP. Retrogradely labelled levator motoneurons were distributed bilaterally throughout the caudal central division of the oculomotor nucleus. A few labelled cells were also present within the contralateral superior rectus division, possibly because of the spread of tracer at the injection site. The possibility that individual motoneurons collateralize to innervate the levator muscle bilaterally was tested by using double retrograde labelling techniques. Doubly labelled levator motoneurons could not be detected by using a combination of tracers (HRP and Fast Blue). Motoneurons innervating the upper lid portion of the orbicularis oculi muscle were distributed within the dorsal subdivision of the ipsilateral facial motor nucleus, with a few neurons in the corresponding locus of the contralateral facial nucleus. Species differences in levator motoneuron distribution, particularly distinctions in lateral-eyed versus frontal-eyed mammals, are discussed in relation to the neural control of lid movements. The levator palpebrae superioris contains three of the same ultrastructurally defined types of singly innervated muscle fiber found in the global layer of other extraocular muscles and an additional, unique slow-twitch fiber type. Moreover, the multiply innervated fiber types so characteristic of the other extraocular muscles are conspicuously absent from levator muscles. Unlike the rectus and oblique extraocular muscles, the levator lacks a layered distribution of fiber types. The morphological profiles of levator muscle fiber types are such that they generally do not respect traditional fiber classification schemes, but are consistent with a role for the levator in sustained elevation of the lid. The orbicularis oculi muscle, by contrast, exhibited three distinct fiber types that resembled categories of skeletal muscle twitch fibers. One slow-twitch and two fast-twitch fiber types were noted. On the basis of oxidative enzyme profiles and mitochondrial content, the majority of orbicularis oculi fibers would be fatigue-prone, an assessment consistent with their rapid onset/offset of acti     

Botulinum toxin injection into Riolan's muscle: somatosensory 'trick'

We studied the effect of injecting botulinum toxin A (BTX-A) into the pars ciliaris--also known as Riolan's muscle--of patients with eyelid apraxia (ELA). Six patients with ELA were treated with injections of BTX-A into the region of Riolan's muscle at the medial and lateral portions of the upper and lower pretarsal orbicularis oculi. Clinical benefit was seen in all 6 patients, 2 of whom had previously been treated with conventional pretarsal injections of BTX-A and had not improved. BTX-A injections into Riolan's muscle are effective as treatment for ELA. The proposed mechanism is not that of muscle relaxation but rather modulation of the somatosensory cortex, similar to that of a 'sensory trick' in patients with dystonia.     

Surface electromyographic study of idiopathic cranial dystonia focused on the orbicularis oculi muscles

We studied 115 Japanese patients with idiopathic cranial dystonia (Meige disease), using surface electromyographu (EMG) focused on the orbicularis oculi muscles to classify the findings of the abnormal involuntary movements of this disease and to evaluate the pathophysiology of blepharospasm (BS). Surface EMGs at rest and at voluntary eyelid opening after eyelid closing were investigated. We found 62 (53.9%) patients exhibiting the overblinking type, 37 (32.2%) the tonic BS type, and 16 (13.9%) the normal type of behavior, considering the frequency of spontaneous blinking and presence of spasms. The present results suggest that BS is not a summation of blinking but a spatial and temporal extension of the orbicularis oculi muscle activity engaging in blinking, and the classification of the present study can support the investigation of the temporal characteristics of patients with this disease.     

The relationship of eyelid movement to the blink reflex

Although the blink reflex is a standard neurophysiological investigation its relationship with eyelid movement has not been clearly established. We studied normal subjects and patients with unilateral facial paralysis to define the pattern of eyelid movement following glabellar tap, supraorbital nerve stimulation, facial nerve stimulation and direct corneal stimulation. We found that eyelid closure did not necessarily occur in a single movement. Following glabellar tap the first component of a two-stage movement was initiated by levator palpebrae relaxation while with supraorbital nerve stimulation orbicularis oculi contraction produced the first movement. The compound muscle action potential following direct facial nerve stimulation produced only minimal eyelid movement, the major closure being associated with a longer latency orbicularis oculi reflex. Corneal stimulation elicited a single component eyelid movement. Thus, the pattern of eyelid movement differed for each stimulus reflecting variations in orbicularis oculi contraction and levator palpebrae inhibition.     

Botulinum-induced alteration of nerve-muscle interactions in the human orbicularis oculi following treatment for blepharospasm

To assess longstanding alterations in human muscle innervation induced by botulinum toxin, we studied motor axons in the orbicularis oculi of nine patients previously injected with botulinum toxin for treatment of benign essential blepharospasm (BEB). Compared with untreated BEB and normal orbicularis oculi, muscle exposed to botulinum toxin developed persistent and cumulative alterations of innervation, including (1) thin, unmyelinated axonal collaterals that contact muscle end plates, (2) an increased number of muscle fibers innervated by individual terminal motor axons, (3) a profusion of unmyelinated axonal sprouts that end blindly, (4) an increased range of end plate sizes, and (5) multiple end plates on individual muscle fibers. The findings suggest that axonal sprouts which develop after botulinum-toxin-induced functional denervation can form new end plates. A single muscle fiber may then be innervated at separate sites by more than one axon.     

Ocular myopathy without ophthalmoplegia can be a form of mitochondrial myopathy.

To characterize muscle pathology in 3 cases affected by ocular myopathy with eyelid ptosis and upper facial weakness, but without ophthalmoplegia, light microscopy and ultrastructural study were performed on levator palpebrae, orbicularis oculi and deltoid muscle biopsies. While levator palpebrae proved uninformative because of the massive fibrous degeneration of muscle, orbicularis oculi biopsies showed histochemical and ultrastructural alterations indicating a mitochondrial involvement, resembling that reported in ocular mitochondrial myopathies (OMM). On the other hand very mild aspecific findings were observed in deltoid. We suggest that these cases with ocular myopathy and without ophthalmoplegia should be considered a partial or initial form of OMM.     

Apraxia of eyelid closure in a patient with progressive supranuclear palsy]

We reported a 68-year-old man with progressive supranuclear palsy who present with apraxia of eyelid closure. He showed horizontal and vertical supranuclear ophthalmoplegia, neck dystonic posture, pseudobulbar palsy and subcortical dementia. He opened his eyes almost all day long except for sleeping. His spontaneous blinking was noted at less than 1 per a minute. Although he closed his eyes reflexively, he could not close his eyes by verbal command. He occasionally closed his eyelids by using both hands. The surface electromyographic (EMG) findings revealed that the frequency of frontal muscle contraction did not decrease, and rather increased during verbal command to close his eyes. The contraction frequency of orbicularis oculi muscle did not increase by the command of voluntary eyelid closure. It is suggested that abnormal contractions of frontalis and orbicularis oculi muscles which are correlated in eyelid closing and opening might contribute to the apraxia of eyelid closure.     

Chronic progressive spinobulbar spasticity with disturbance of voluntary eyelid closure. Report of a case with special reference to MRI and electrophysiological findings

We describe a 56-year-old man who had a progressive pseudobulbar palsy, spastic tetraparesis, forced laughing and disturbance of voluntary eyelid closure, and was clinically compatible with chronic progressive spinobulbar spasticity. Magnetic resonance images (MRI) revealed atrophy of the bilateral motor cortices and single photon emission tomography after intravenous injection of N-isopropyl-p-iodoamphetamine iodine-123 (IMP-SPECT) showed hyporadioactivity in the same regions. Electrophysiological studies on supranuclear paralysis of eyelid closure demonstrated that so-called apraxia and motor impersistence coexisted and that in attempts to keep the eyelid closed the inhibition of basal activity of the levator palpebrae superioris muscle and activation of the orbicularis oculi muscle were insufficient, indicating the impaired reciprocity of these ocular muscles. The corresponding lesion of these eyelid symptoms was considered to be the bilateral motor cortices.     

A silent period in orbicularis oculi muscles of humans.

Surface electromyographic activity was recorded bilaterally from orbicularis oculi muscles when subjects relaxed and contracted eyelid muscles. Cutaneous reflex responses were evoked during both the relaxed and contraction states. Following reflex elicitation periods of muscle silence in orbicularis oculi were observed for about 10 to 15 ms after the ipsilateral R1 response and for up to 100 ms after the bilateral R2 responses. Reflex responses appeared to be enhanced when elicited during contractions. Possible physiological mechanisms are discussed regarding the presence of silent periods in a motor system that is presumably devoid of spindles, Golgi tendon organs, and Renshaw-like interneurons.     

No clinical or neurophysiological evidence of botulinum toxin diffusion to non-injected muscles in patients with hemifacial spasm

Botulinum toxin injected into a muscle may diffuse to nearby muscles thus producing unwanted effects. In patients with hemifacial spasm, we evaluated clinically and neurophysiologically, whether botulinum toxin type A (BoNT-A) diffuses from the injection site (orbicularis oculi) to untreated muscles (orbicularis oris from the affected side and orbicularis oculi and oris from the unaffected side). We studied 38 patients with idiopathic hemifacial spasm. Botulinum toxin was injected into the affected orbicularis oculi muscle alone (at 3 standardized sites) at a clinically effective dose. Patients were studied before (T0) and 3-4 weeks after treatment (T1). We evaluated the clinical effects of botulinum toxin and muscle strength in the affected and unaffected muscles. We also assessed the peak-to-peak amplitude compound muscle action potential (CMAP) recorded from the orbicularis oculi and orbicularis oris muscles on both sides after supramaximal electrical stimulation of the facial nerve at the stylomastoid foramen. In all patients, botulinum toxin treatment reduced muscle spasms in the injected orbicularis oculi muscle and induced no muscle weakness in the other facial muscles. The CMAP amplitude significantly decreased in the injected orbicularis oculi muscle, but remained unchanged in the other facial muscles (orbicularis oris muscle on the affected side and contra-lateral unaffected muscles). In conclusion, in patients with hemifacial spasm, botulinum toxin, at a clinically effective dose, induces no clinical signs of diffusion and does not reduce the CMAP size in the nearby untreated orbicularis oris or contralateral facial muscles.     

建立人工面神经反射弧恢复失神经支配眼轮匝肌的闭眼功能

目的：建立人工面神经反射弧,恢复面瘫兔的闭眼功能。 方法：试验动物为新西兰兔12只。采用手术切断面神经制备单侧周围性面瘫模型,患侧行肌电图检查确诊。术后第5天患侧植入刺激电极,健侧植入采集电极并留置1月。患侧分别于术后第7天、第28天给予电流刺激;而健侧采集电极则连续采集2周的肌电信号。建立健侧眼轮匝肌肌电信号采集、中枢信号处理模式识别、患侧电流刺激眼轮匝肌系统。当健侧眼轮匝肌采集的肌电信号经信号识别、提取以及电脑分析判断,符合其闭眼刺激阈值时,即对人工电刺激器发出指令,由刺激电极直接作用于患侧眼轮匝肌,引起眼睑完全闭合。结果：刺激方式为正负方向矩形波,电流强度为0.40—0.70mA之间可引起患侧眼轮匝肌收缩,眼睑完全闭合。当健侧眼睑闭合时,其肌电信号电压大于50uV,触发电刺激器,电流刺激即引发患侧眼轮匝肌收缩,完成眼睑闭合。结论：利用MEMS技术,在面瘫兔模型建立“人工面神经反射弧”,恢复患侧眼轮匝肌闭眼功能。     

Restoration of orbicularis oculi function by contralateral orbicularis oculi innervated muscle flap vs neuromuscular pedicle technique.

In preliminary experiments with dogs and cats, unilateral paralysis of the orbicularis oculi muscle group was produced by a section of the seventh nerve that included the posterior auricular branch. Either one of two procedures was then employed in attempts to reinnervate the paralyzed eyelid. In one group of animals, a neuromuscular pedicle was employed and in another, a contralateral orbicularis innervated muscle flap was used. Both methods restored synchronous, reflex blinking to the denervated eyelid. Of the two procedures, neurotization appears to offer the greater promise because the use of a neuromuscular pedicle requires an expendable nerve that is functional, and no such suitable substitute is available in humans.     

The combined treatment with orbital and pretarsal botulinum toxin injections in the management of poorly responsive blepharospasm

Blepharospasm (BS) is a focal dystonia involving involuntary contractions of muscles around the eyes. Botulinum toxin (BoNT) is the most effective treatment for BS and the technique of injection changes depending on the clinical picture. Usually typical BS benefits from the injection in the orbital part of the orbicularis oculi (OOc) muscle (orbital injection), while BoNT injection in the pretarsal part of OOc muscle is helpful especially for the atypical BS (opening eyelid apraxia). The aim of this study was to compare the efficacy of two injection techniques, the orbital versus the combined (injection in both orbital and pretarsal part of OOc) in BS patients with unsatisfactory response to BoNT. Nineteen patients with typical BS not having a satisfactory response from BoNT treatment with the orbital injection (primary and secondary resistant patients) were studied. After 3 months from the last orbital injection patients received the combined injection; they were assessed with the JRS and BSDI scales after 4 weeks from the last orbital and the first combined injection. Statistical analysis showed a significant reduction (p < 0.05) of the mean score of JRS and BSDI scales comparing the combined with orbital injection. This study shows that the treatment of typical BS can have better results when BoNT is injected with the combined technique in primary and secondary resistant patients.     

A regional histochemical and electromyographic analysis of the cat respiratory diaphragm

We analyzed the fiber type composition and pattern of electromyogram (EMG) activity in selected regions of the cat diaphragm. The muscles were composed of three basic fiber types. The percentages of each type varied markedly between and within the different regions. The muscle bordering the esophageal hiatus was highest in slow-twitch oxidative (SO) fibers, which appeared specialized to constrict the esophagus and help prevent gastroesophageal reflux. The hiatal muscle was also unique because it received bilateral phrenic motor innervation. Fiber type composition and EMG activity patterns correlated in a consistent manner, i.e., the areas highest in SO fibers yielded patterns of activity characteristic of low-threshold, tonic motor units and the regions lowest in SO and highest in fast glycolytic fibers generated patterns of activity distinctive of high-threshold, phasic motor units. All areas were electrically silent during expiration. Thus, our findings further substantiate the striking nonhomogeneous composition of the diaphragm and indicate that this heterogeneity is a consequence of regional specialization of function.     

Stimulated single-fiber EMG of the frontalis and orbicularis oculi muscles in ocular myasthenia gravis

We performed single-fiber electromyography by axonal stimulation (stimulated SFEMG) of the frontalis and orbicularis oculi muscles of 20 patients with ocular myasthenia gravis (OM) and 46 controls. In controls, mean consecutive differences (MCD) ranged from 5 to 55 micros (average, 14.7 +/- 2.8 micros) in the frontalis and from 4 to 56 micros (average, 12.56 +/- 2.19 micros) in orbicularis oculi. The mean MCD of individual muscle potentials (MPs) was 14.6 +/- 6.8 micros in frontalis and 12.68 +/- 6.10 micros in orbicularis oculi. In the OM patients, the mean MCD was 43.85 +/- 25.18 micros in the frontalis and 69.85 +/- 29.55 micros in orbicularis oculi (P < 0.0001), and the number of MPs with altered MCD was 7.15 +/- 4.66 (range, 1-18) and 12.65 +/- 4.90 (range, 6-21), respectively (P < 0.0001). We conclude that stimulated SFEMG of the orbicularis oculi muscle is more sensitive for the diagnosis of OM than of the frontalis muscle.     

Gaze-evoked eyelid closure. Report of two cases

Various types of associated movements of eyeballs with other cranial muscles have been described in the literature. Only a few observations, however, have been reported on the relation of ocular movements and facial muscles innervated by the facial nerve, especially the orbicularis oculi muscles. We report two cases presenting gaze-evoked involuntary contraction of the orbicularis oculi muscle and unilateral eyelid closure. Case 1 was a 38-year-old housewife who was admitted to our hospital because of gait disturbance and sensory deficits below the neck. She had a 5-year history of left facial palsy, disturbed horizontal eye movements, retrobulbar optic neuritis, spastic paraparesis and bladder and rectal disturbances, some of which had relapsed a few times. Neurological abnormalities were summarized as follows: bilateral pale discs, right Horner's sign, horizontal nystagmus, left facial nerve palsy of peripheral type, spastic paraparesis with left-sided predominance, sensory disturbances below the third cervical segment, truncal and limb ataxia, and bladder and rectal disturbances. Gaze-linked synchronized contraction of the left facial muscles was observed and on the left lateral gaze marked spasm of the left orbicularis oculi muscle with occasional lid closure was evoked. Case 2 was a 72-year-old female with cerebellar hemorrhage. Neurological abnormal findings included mild disorientation, meningeal irritation signs, horizontal nystagmus on lateral gaze, reduced response of reflex eye movement to the left, minimal weakness of the left facial muscles, ataxic dysarthria, mild left hemiparesis and hemisensory deficits with face, truncal and limb ataxia. She could move eyeballs to any direction but with effort to the left.(ABSTRACT TRUNCATED AT 250 WORDS)