The Effects of Botulinum Toxin a on Ephaptic Transmission in Idiopathic Hemifacial Spasm

Objective: Lateral spreading and synkinetic responses of blink reflex are a sign of ephaptic transmission in idiopathic hemifacial spasm (HFS). The aim of this study was to evaluate the effect of botulinum toxin A (Btx A) on ephaptic transmission in idiopathic HFS. Methods: Thirty-three patients with idiopathic HFS were investigated. Btx A was injected only into the affected orbicularis oculi (OC) muscle. Electrophysiological studies were performed before and three weeks after the Btx A injection. Results: After Btx A, the latencies of motor response and blink reflexes elicited from the OC muscle were significantly increased. The lateral spreading was not obtained in the OC muscle, while the orbicularis oris muscle response was not changed. There were no significant differences in the synkinetic responses of blink reflex. During needle EMG examination, positive sharp waves and fibrilation potentials were observed due to chemodenervation only in the OC muscle. Conclusion: Btx A affects only the neuromuscular junctions of the injected muscle and has no effect upon ephaptic transmission.     

Blink reflexes and lateral spreading in patients with synkinesia after Bell's palsy and in hemifacial spasm

We compared various electrodiagnostical tests in patients with hemifacial spasm and in patients who developed synkinesia after Bell's palsy. We examined the evoked blink reflexes in the orbicularis oculi (o. oculi) and orbicularis oris (o. oris) muscles in 23 patients with hemifacial spasm (HFS), in 10 patients with synkinesia after Bell's palsy (BPS) and in 22 control subjects. In the patient groups, we recorded synkinesia, latency and amplitude of compound muscle action potential (CMAP) in the mental muscle after stimulation of the facial nerve and we examined electromyographic activity of the o. oculi and mental muscles synchronously. Furthermore, we studied the phenomenon of lateral spreading, also known as ephaptic transmission, between the different facial nerve branches. Patients with BPS had a prolonged R1 latency on the affected side in o. oculi and smaller mental CMAP amplitude as an indication of facial nerve damage and nerve fiber loss. This was not found in patients with HFS, who showed an increased amplitude of the R1 and R2 responses in o. oris. Patients with BPS showed only an increased R1 amplitude in o. oris. All patients had signs of synkinesia. Lateral spreading with different patterns was present in all patients with HFS and in half of the patients with BPS. Latencies of early and late responses showed no differences between HFS and BPS. In addition to alterations in facial nucleus excitability in both conditions, ectopic re-excitation of facial nerve axons in HFS may explain the differences in neurophysiological findings between HFS and BPS patients. A loss of control following synaptic stripping may also be a contributing factor.     

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.     

Experimental study on the correlation between abnormal muscle responses and F waves in hemifacial spasm

OBJECTIVES: To investigate the correlation between abnormal muscle response (AMR) and F wave by establishing an animal model of hemifacial spasm (HFS). METHODS: Both demyelination in the main trunk of the facial nerve just distal to stylomastoid foramen and vascular compression were used to duplicate animal model of HFS in ten New Zealand white rabbits. AMR and F waves were elicited from the orbicularis oculi and mentalis muscles respectively by stimulating marginal mandibular branch of the facial nerve 6 weeks post-operatively. Correlation analyses were used to compare the relationship between AMR/M and F/M amplitude ratio and between the duration of AMRs and F waves. RESULTS: There was a linear correlation between the mean values of the AMR/M and F/M amplitude ratio (r=0.8602, p<0.01), which can also be found between the duration of AMRs and F waves (r=0.7702, p<0.01). DISCUSSION: Enhanced F waves and AMRs may have the same origin. The F wave can be regarded as a more direct index in the diagnosis pre-operatively, monitoring intraoperatively and follow-up post-operatively in patients with HFS.     

Botulinum toxin treatment of synkinesia and hyperlacrimation after facial palsy

OBJECTIVES—Toinvestigate the effects of injection of botulinum toxin type A (BTX A)into the orbicularis oculi muscle and lacrimal gland in patients withaberrant regeneration after facial palsy (facial synkinesias and hyperlacrimation).
METHODS—The effect ofthe toxin injection (on average 75 mouse units of BTX A) into theorbicularis oculi muscle on facial synkinesias was assessed on a fivepoint (0 to 4) scale in 10 patients with aberrant regeneration offacial nerve fibres after a peripheral facial nerve palsy. Six patientsunderwent a videographic control, which was assessed by a blindedindependent investigator. In two patients with hyperlacrimation anextra dose of botulinum toxin (on average 20 mouse units BTX A) wasinjected into the lacrimal gland and the effect was assessed using theSchirmer test and on a three point scale.
RESULTS—Botulinumtoxin type A had a good to excellent (grades 3 and 4) effect over anaverage of six months after 91% of injections. In 9% the injectionshad a moderate (grade 2) effect. Patients with hyperlacrimation showeda nearly complete recovery. There were no systemic side effects butfocal side effects due to a temporary weakness of the orbicularis oculimuscle were not uncommon.
CONCLUSIONS—Botulinumtoxin type A is the treatment of choice in motor and autonomic effectsof aberrant regeneration of facial nerve after a peripheral palsy. Therequired dose is similar to or slightly lower than the dose usuallyrecommended for hemifacial spasm.

     

Electrophysiological study of ephaptic axono-axonal responses in hemifacial spasm

One of the classic features of hemifacial spasm (HFS) is spread of the blink reflex responses to muscles other than the orbicularis oculi. The pathophysiological mechanisms underlying the generation of such abnormal responses include lateral spread of activity between neighboring fibers of the facial nerve and hyperexcitability of facial motoneurons. In this report we present evidence for another mechanism that can contribute to the generation of responses in lower facial muscles resembling the R1 response of the blink reflex. In 13 HFS patients, we studied the responses induced in orbicularis oris by electrical stimuli applied at various sites between the supraorbital and zygomatic areas. We identified responses with two different components: an early and very stable component, with an onset latency ranging from 10.5 to 14.8 ms, and a more irregular longer-latency component. Displacement of the stimulation site away from the supraorbital nerve and towards the extracranial origin of the facial nerve caused a progressive shortening of response latency. These features indicate that, in our patients, the shortest latency component of the orbicularis oris response was likely generated by antidromic conduction in facial nerve motor axons followed by axono-axonal activation of the fibers innervating the lower facial muscles. Our results suggest that motor axono-axonal responses are generated by stimulation of facial nerve terminals in HFS.     

Lack of effect of botulinum toxin on cortical excitability in patients with cranial dystonia

The aim of this study was to verify whether botulinum toxin (BTX)-induced clinical improvement of cranial dystonia is associated with changes in the cortical silent period (SP), a measure of cortical excitability. By transcranial magnetic stimulation (TMS), high-intensity stimuli were delivered with a round coil centered at the vertex during a maximal muscle contraction of the orbicularis oculi. Motor evoked potentials (MEPs) and SPs were obtained from surface electrodes placed over the orbicularis oculi muscle before and 2 to 3 weeks after BTX-A injection into the affected muscles in 10 patients with cranial dystonia and 8 age-matched control subjects. BTX injection improved blepharospasm in all patients. Facial muscle SPs were significantly shorter in patients than in control subjects and did not significantly change after treatment, at the time of maximal clinical improvement. We conclude that the clinical improvement induced by BTX in patients with cranial dystonia is largely symptomatic. It does not appear to result from modulation of abnormal aspects of intracortical excitability, although these may play a role in craniofacial dystonia.     

Lateral spread response elicited by double stimulation in patients with hemifacial spasm

In patients with hemifacial spasm (HFS), a lateral spread response (or abnormal muscle response) is recorded from facial muscles after facial nerve stimulation. The origin of this response is not completely understood. We studied the lateral spread responses elicited by double stimulation in 12 patients with HFS during microvascular decompression. The response was recorded from the mentalis muscle by electrical stimulation of the temporal branch of the facial nerve or from the orbicularis oculi muscles by stimulation of the marginal mandibular branch. The interstimulus intervals (ISIs) of double stimulation ranged from 0.5 to 7.0 ms. R1 was defined as the response elicited by the first stimulus, and R2 as the response elicited by the second stimulus. R1 had a constant latency and amplitude regardless of the ISI, whereas R2 appeared after a fixed refractory period without facilitation or depression in a recovery curve of latency and amplitude. From these findings, we consider that the lateral spread response is due to cross-transmission of facial nerve fibers at the site of vascular compression rather than arising from facial nerve motor neurons.     

偏侧面肌痉挛和良性特发性眼睑痉挛的临床与治疗特点

目的 探讨偏侧面肌痉挛(HFS)和良性特发性眼睑痉挛(BEB)的临床特点、治疗现状以及对A型肉毒毒素(BTX-A)治疗的反应.方法 对2013年4~10月在武汉大学人民医院神经内科门诊就诊的HFS患者和BEB患者进行调查,其中HFS患者110例,BEB患者90例.所有的患者均接受了BTX-A局部注射治疗.注射后2周左右复诊,在每周二下午的专病门诊随访,并记录BTX-A的疗效持续时间.结果(1)入组200例患者中,BTX-A治疗起效时间0~30 d(中位数4 d),疗效持续时间2~128周(中位数16周),总有效率96.9%.HFS患者症状明显好转(完全和明显缓解)占99.3%,BEB患者占90.2%.总的来说,BEB患者的疗效持续时间[(13.6±5.5)周]与HFS患者[(20.3±10.2)周]相比较短.HFS患者所用BTX-A剂量[(53.2±15.8)U]较BEB患者[(74.8±20.2)U]少.(2)BTX-A注射(70.9%)、针灸(68.2%)和口服药(65.5%)是HFS患者曾经选择的最多的非手术治疗方法.针灸和口服药大部分效果不好而自行停用.BTX-A注射(88.9%)、口服药(86.7%)和眼轮匝肌切割术(31.1%)是BEB患者曾经选择的最多的治疗方法,但患者均反映手术无效.结论 HFS和BEB是运动障碍门诊最常见的两种疾病,BTX-A治疗HFS和BEB安全、有效,对HFS效果更好,BEB患者需要更频繁的注射,其面部肌张力障碍的治疗更具挑战性.     

Reflex excitability of facial motoneurons at onset of muscle reinnervation after facial nerve palsy.

We studied 18 patients with complete unilateral denervation of the facial muscles after idiopathic facial nerve palsy to determine whether motoneuronal excitability is enhanced in the few motor units that are active at onset of muscle reinnervation. The study was carried out between 75 and 90 days after the facial nerve lesion. We used two needle electrodes to record simultaneously the spontaneous and voluntary activity of the orbicularis oris (OOris) and orbicularis oculi (OOculi) muscles, as well as the responses to ipsilateral and contralateral facial and supraorbital nerve stimuli. All patients showed involuntary firing of motor unit action potentials (MUAPs) in at least one of the muscles. Synkinetic activation of motor units in the OOris was induced by spontaneous blinking in all patients, and by inhalation and swallowing in some. Electrical stimulation of the ipsilateral facial nerve induced a direct M response in only 4 patients. In contrast, long-latency reflex responses were induced in both muscles by electrical stimulation of ipsilateral and contralateral facial and supraorbital nerves in all patients, at latencies ranging between 44 and 132 ms. The shape of such MUAP reflex responses was the same as that of the MUAPs seen to fire at rest. These findings provide evidence of enhanced excitability of facial motoneurons in our patients. Such hyperexcitability may be partly responsible for the postparalytic motor dysfunction syndrome that occurs after facial palsy with severe axonal damage.     

面肌痉挛显微血管减压术的诱发肌电图监测和评估

目的:探讨面神经诱发肌电图在显微血管减压(MVD)术中、术后对面肌痉挛治疗效果的监测和评估。方法:对26例典型面肌痉挛病人、探讨在MVD术前、术中、术后,经皮刺激痉挛侧(手术侧)面神经下颌缘支,记录诱发同侧眼轮匝肌肌电位(MD-OC反应)变化,并以正常侧作对照检查。结果:26例术前均记录到痉挛侧MD-OC反应,在术中操作不同阶段,21例均见MD-OC反应消失。术后1周～3个月随访复查21例中,12例痉挛完全消失,MD-OC反应不复存在,9例症状明显或部分减轻,但有4例再记录到MD-OC反应。另5例术中,术后均记录到MD-OC反应,症状未有改善。结论:面神经诱发肌电图运用于MVD术中监测和预后判断,可改善和提高面肌痉挛的治愈率。     

Intra-operative neurophysiology during microvascular decompression for hemifacial spasm

There is evidence that primary hemifacial spasm (HFS) in the majority of patients is related to a vascular compression of the facial nerve at its root exit zone (REZ). As a consequence, the hyperexcitability of facial nerve generates spasms of the facial muscles. Microvascular decompression (MVD) of the facial nerve near its REZ has been established as an effective treatment of HFS. Intra-operative disappearance of abnormal muscle responses (lateral spread) elicited by stimulating one of the facial nerve branches has been used as a method to predict MVD effectiveness. Other neurophysiologic techniques, such as facial F-wave, blink reflex and facial corticobulbar motor evoked potentials (FCoMEP), are feasible to intra-operatively study changes in excitability of the facial nerve and its nucleus during MVDs. Intra-operative neuromonitoring with the mentioned techniques allows a better understanding of HFS pathophysiology and helps to optimise the MVD.     

Trigemino-facial inhibitory reflexes in idiopathic hemifacial spasm.

We investigated trigemino-facial excitatory and inhibitory responses in perioral muscles in hemifacial spasm (HFS). We examined 15 patients affected with idiopathic HFS and 8 healthy controls. Five patients had spasms mostly limited to the periocular region and 10 had spasms also involving the perioral muscles. Responses were recorded from the resting orbicularis oculi (OOc), levator labii superioris (LLS) and orbicularis oris (OOr) muscles, after supraorbital (SO) nerve stimulation and during isolated voluntary contraction of LLS muscle. Eight patients showed complete or partial preservation of the late silent period (SP2) in activated LLS muscle. The remaining 7 patients showed absence of SP2. Early and late excitatory responses were variably present in LLS muscle at rest. Patients with HFS clinically restricted to periocular muscles had at least partial preservation of the SP2. In conclusion, in HFS patients inhibitory trigemino-facial reflexes are impaired and excitatory trigemino-facial responses are elicited in perioral muscles. These two phenomena seem to develop independently; the degree of trigemino-facial reflex impairment parallels the extension of involuntary movements to the lower facial muscles.     

Functional end-plate recovery in long-term botulinum toxin therapy of hemifacial spasm: a nerve conduction study

Botulinum toxin type-A is currently thought to be effective and safe for hemifacial spasm (HFS). The pre-synaptic block of acetylcholine release at the neuromuscular junction induces depression of orbicularis oculi muscle compound motor action potential (CMAP). The aim of our study was to evaluate at what extent end-plate functional recovery is possible even in botulinum toxin treatments lasting up to 15 years. We examined 81 outpatients with primary HFS (mean treatment duration = 7.2 ± 4.2 years) who underwent neurophysiologic study, once clinical effect of the previous treatment had vanished. The mean CMAP amplitude, mean rectified amplitude of response 1 (R1) of the blink reflex and area of response 2 (R2) of treated orbicularis oculi muscle were measured in comparison to the controlateral side. Mean amplitude of the above mentioned parameters was slightly lower (about 20%; p < 0.001) in the treated side at the end of the follow-up period (4.7 ± 1.7 months). The CMAP amplitude reduction weakly correlated with the interval from last treatment, while other neurophysiologic parameters did not change due to treatment duration or total toxin amount. Our study demonstrates that botulinum toxin affects compound motor action potential and blink-reflex responses for at least 4–5 months in HFS patients. The residual block is slight and does not increase with repeated injections after several years of treatment. Our study, beside confirming the long-term efficacy of botulinum toxin treatment for HFS, provides neurophysiologic evidence that therapeutic effect may be obtained without hindering the regenerative potential of the nerve-muscle complex.     

Afferent projections to the orbicularis oculi motoneuronal cell group. An autoradiographical tracing study in the cat

The motoneurons innervating the orbicularis oculi muscle from a subgroup within the facial nucleus, called the intermediate facial subnucleus. This makes it possible to study afferents to these motoneurons by means of autoradiographical tracing techniques. Many different injections were made in the brainstem and diencephalon and the afferent projections to the intermediate facial subnucleus were studied. The results indicated that these afferents were derived from the following brainstem areas: the dorsal red nucleus and the mesencephalic tegmentum dorsal to it; the olivary pretectal nucleus and/or the nucleus of the optic tract; the dorsolateral pontine tegmentum (parabrachial nuclei and nucleus of K?lliker-Fuse) and principal trigeminal nucleus; the ventrolateral pontine tegmentum at the level of the motor trigeminal nucleus; the caudal medullary medial tegmentum; the lateral tegmentum at the level of the rostral pole of the hypoglossal nucleus and the ventral part of the trigeminal nucleus and the nucleus raphe pallidus and caudal raphe magnus including the adjoining medullary tegmentum. These latter projections probably belong to a general motoneuronal control system. The mesencephalic projections are mainly contralateral, the caudal pontine and upper medullary lateral tegmental projections are mainly ipsilateral and the caudal medullary projections are bilateral. It is suggested that the different afferent pathways subserve different functions of the orbicularis oculi motoneurons. Interneurons in the dorsolateral pontine and lateral medullary tegmentum may serve as relay for cortical and limbic influences on the orbicularis oculi musculature, while interneurons in the ventrolateral pontine and caudal medullary tegmentum may take part in the neuronal organization of the blink reflex.     

Hemifacial spasm due to a tentorial paramedian meningioma: a case report

Abstract Hemifacial spasm (HFS) is a movement disorder characterised by involuntary paroxysmal facial movements that usually involve the orbicularis oculi and then spread to the other facial muscles. A microvascular compression and demyelination of the seventh nerve at its exit from the brain stem is considered to be the main aetiology of HFS. In addition to rare idiopathic (cryptogenetic) cases, others causes of HFS exist: tumours or vascular malformations have been described, of both the ipsilateral and contralateral cerebellopontine angle (CPA). However, space-occupying lesions in locations other than CPA are usually not thought to be responsible for HFS. Here we describe the case of a 45-year-old woman suffering from HFS, who dramatically improved after surgical removal of a tentorial paramedian meningioma.     

Electrophysiological study on hemifacial spasm--usefulness in the etiological diagnosis and pathophysiological mechanism

Electrophysiological studies were performed in 30 patients with idiopathic hemifacial spasm (idiopathic HFS), who underwent microvascular decompression with abolishment of spasm, and 10 patients with symptomatic hemifacial spasm (symptomatic HFS) secondary to Bell's palsy. (1) The maximum firing rate of abnormal discharges recorded from the orbicularis oris muscle during spasm in patients with idiopathic and with symptomatic HFS, and that of discharges recorded on the intact side during voluntary contraction in idiopathic HFS patients measured 181 +/- 71 Hz, 68.4 +/- 36.9 Hz, 56.3 +/- 21.8 Hz, respectively. Thus, the maximum firing rate of the discharges during spasm in idiopathic HFS patients was exceedingly higher than that in symptomatic HFS patients. (2) Electroneurography, performed to evaluate quantitatively degeneration of the facial nerve, revealed that the ENoG value (90.2 +/- 16.5%) in idiopathic HFS patients were higher than that (57.6 +/- 26.8%) in symptomatic HFS patients. (3) In blink reflex examined, synkinetic potentials (S1, S2), synchronous to the potentials consisting of the early (R 1) and late component (R 2) in the orbicularis oculi muscle, were recorded from the orbicularis oris muscle on the affected side in all patients with idiopathic and with symptomatic HFS. In sequential recording of blink reflex potentials (R 1, R 2) and synkinetic potentials (S 1, S 2), the recording pattern of synkinetic potentials was divided into variable and constant type. In the variable type, synkinetic potentials appeared unsteadily and the difference in latency between R 1 and S 1 was varied. In the constant type, synkinetic potentials appeared steadily and the difference in latency between the two was not varied.(ABSTRACT TRUNCATED AT 250 WORDS)     

长期重复应用A型肉毒毒素治疗面肌痉挛对面神经传导速度及CMAP的影响

目的 探讨长期重复应用A型肉毒毒素治疗面肌痉挛（Hemifacial spasm,HFS）对面神经电生理功能的影响.方法 将44例HFS患者分别依据病程及接受肉毒毒素治疗的次数分为3组：早期组（16例）、长期未治疗组（10例）、长期重复治疗组（18例）,并测量患者双侧面神经传导速度及复合肌肉动作电位波幅.结果 长期重复治疗组面神经诱发肌电图的CMAP波幅患侧较健侧显著降低,其余2组CMAP（Compound muscle action potential）波幅及3组患者潜速率患健侧自身对比均无显著性差异.结论 长期A型肉毒毒素局部注射治疗HFS安全、疗效显著,且降低治疗侧的CMAP波幅对面神经传导速度无明显影响.     

Blink reflex in patients with hemifacial spasm. Observations during microvascular decompression operations

The blink reflex cannot normally be elicited during surgical anesthesia using inhalation anesthetics. However, in patients with hemifacial spasm (HFS) the early component of the reflex response (R1) can be elicited on the affected side but not on the unaffected side during such anesthesia. The electromyographic (EMG) response from the mentalis muscle to stimulation of the supraorbital nerve was recorded during microvascular decompression (MVD) of the facial nerve to relieve HFS and compared to the response from the same muscle to stimulation of the zygomatic branch of the facial nerve in four patients. During the operation before the facial nerve was decompressed, contractions in both the orbicularis oculi and the mentalis muscles could be elicited by stimulation of the supraorbital nerve (mean latencies 12.2 +/- 1.9 and 12.9 +/- 2.0 ms, respectively). When the facial nerve had been decompressed the blink reflex could no longer be elicited, and there was no response from the mentalis muscle to stimulation of the zygomatic branch of the facial nerve. Compound action potentials (CAP) recorded from the 7th cranial nerve in response to stimulation of the supraorbital nerve had latencies of 7.5 ms +/- 1.4 ms to the negative peak.     

A pretectofacial projection in the cat: a possible link in the visually-triggered blink reflex pathways

A direct projection from the pretectum to the facial motor nucleus was shown to exist in the cat by the anterograde and retrograde horseradish peroxidase (HRP) methods. Pretectofacial fibers arise from the olivary pretectal nucleus and end mainly in the dorsal division of the facial motor nucleus, bilaterally, with a contralateral predominance. It is known that the olivary pretectal nucleus receives retinal fibers, and that the dorsal division of the facial motor nucleus contains orbicularis oculi motoneurons. Thus, the pretectofacial fibers are assumed to cause protective lid closure with certain visual stimuli.